PMID- 24209964 TI - The AALAS journals: 2012 in review. PMID- 24209965 TI - Trichodina xenopodus, a ciliated protozoan, in a laboratory-maintained Xenopus laevis. AB - A postmortem evaluation of a domestically bred, adult, female Xenopus laevis revealed the presence of a urinary bladder protozoan consistent with Trichodina xenopodus. T. xenopodus is considered an incidental finding, as its presence in the urinary bladder in frogs has not been correlated with disease or with urinary bladder epithelial lesions. Trichodina spp. are ciliated protozoa known to colonize many species of amphibians and fish. These protozoa frequently inhabit the skin and gills, but may also be present in the urinary bladder of infected animals. Their presence on the skin and gills in low numbers is not related to disease; however, large numbers may indicate poor water quality and overcrowding. PMID- 24209966 TI - Predictive observation-based endpoint criteria for mice receiving total body irradiation. AB - Total body irradiation of mice is a commonly used research technique; however, humane endpoints have not been clearly identified. This situation has led to the inconsistent use of various endpoints, including death. To address this issue, we refined a cageside observation-based scoring system specifically for mice receiving total body irradiated. Male and female C57BL/6 mice (age, 8 wk) received 1 of 3 doses of radiation from 1 of 2 different radiation sources and were observed for progression of clinical signs. All mice were scored individually by using cageside observations of their body posture (score, 0 to 3), eye appearance (0 to 3), and activity level (0 to 3). Retrospective analysis of the observation score data indicated that death could be predicted accurately with total scores of 7 or greater, and observation scores were consistent between observers. This scoring system can be used to increase the consistent use of endpoint criteria in total body murine irradiation studies and ultimately to improve animal welfare. PMID- 24209967 TI - Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice. AB - Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID- 24209968 TI - Leukotoxin kills rodent WBC by targeting leukocyte function associated antigen 1. AB - Leukotoxin is a protein that is secreted by Aggregatibacter actinomycetemcomitans and that primarily targets the active form of leukocyte function associated antigen 1 (LFA1) on WBC. Because of its specificity for WBC, leukotoxin is being developed as a novel biologic treatment for hematologic malignancies and autoimmune-inflammatory diseases. Early studies indicated that leukotoxin is specific for WBC from humans and Old World primates. In the current study, we used in vivo and in vitro assays to show that leukotoxin has a wider host range than previously believed and can kill rodent WBC. Administration of leukotoxin to rats and mice resulted in a rapid drop in WBC number but had no effect on RBC or platelet counts. Using LFA1-knockout mice, we showed that leukotoxin-mediated depletion of WBC is dependent on LFA1. In addition, similar to its effect on human monocytes, leukotoxin kills murine myeloid leukemia via a lysosome-mediated pathway that is dependent on cathepsin D. This newly described broader host range of leukotoxin enables the biology of the protein to be studied in rodent species and offers the possibility of using rodent models for evaluating the therapeutic efficacy of leukotoxin in various diseases. PMID- 24209969 TI - Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse. AB - An 8-mo-old female transgenic adenocarcinoma of the mouse prostate (C57BL/6 Tg(TRAMP)8247Ng/J) mouse presented with abdominal distention, lethargy, and serosanguineous vaginal discharge. A large primary renal tumor with metastases to lung and liver was present at necropsy. The tumor was composed of poorly differentiated and crowded epithelial cells forming ducts, acini, and cribriform patterns, with comedonecrosis and frequent bizarre mitoses. Immunohistochemistry revealed that neoplastic cells expressed nuclear SV40 T antigen, confirming aberrant expression of the transgene. In addition, cells were positive for pancytokeratin and negative for synaptophysin and estrogen and progesterone receptors. This report details the first transgene-induced tumor in a female TRAMP mouse. PMID- 24209970 TI - Multiple complex congenital malformations in a rabbit kit (Oryctolagus cuniculi). AB - Congenital malformations may occur during early embryogenesis in cases of genetic abnormalities or various environmental factors. Affected subjects most often have only one or 2 abnormalities; subjects rarely have several unrelated congenital defects. Here we describe a case of a stillborn New Zealand white rabbit with multiple complex congenital malformations, including synophthalmia, holoprosencephaly, gastroschisis, and a supernumerary hindlimb, among other anomalies. There was no historical exposure to teratogens or other known environmental causes. Although not confirmed, this case was most likely a rare spontaneous genetic event. PMID- 24209971 TI - Polymorphisms in canine platelet glycoproteins identify potential platelet antigens. AB - Human alloimmune thrombocytopenic conditions caused by exposure to a platelet specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (beta3), GPIIb (alphaIIb), and GPIbbeta, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes. A secondary objective was to perform a pilot study to assess possible association between specific alleles of these proteins and a diagnosis of idiopathic thrombocytopenic purpura (ITP) in dogs. By using genomic DNA from dogs of various breeds with and without ITP, sequencing of PCR products encompassing all coding regions and exon intron boundaries for these 3 genes revealed 4 single-nucleotide polymorphisms in ITGA2B resulting in amino acid polymorphisms in the canine genome, 3 previously reported and 1 newly identified (Gly[GGG]/Arg[AGG] at amino acid position 576 of ITGA2B. Of 16 possible ITGA2B protein alleles resulting from unique combinations of the 4 polymorphic amino acids, 5 different protein isoforms were present in homozygous dogs and explain all of the genotype combinations in heterozygous dogs. There was no amino acid polymorphism or protein isoform that was specific for a particular breed or for the diagnosis of ITP. PMID- 24209972 TI - Model for concomitant microdialysis sampling of the pons and cerebral cortex in rhesus macaques (Macaca mulatta). AB - Pediatric diffuse intrinsic pontine gliomas are aggressive brainstem tumors that fail to respond to treatment. We hypothesize that the protective features of the pons may hinder chemotherapeutic agents from entering pontine tissue compared with cortical brain tissue. To test this hypothesis, we developed a unique nonhuman primate model using microdialysis, a continuous in vivo extracellular sampling technique, to compare drug exposure concurrently in pontine tissue, cortical tissue, CSF, and plasma after intravenous administration of chemotherapeutic agents. The surgical coordinates and approach for microdialysis cannula-probe placement were determined in 5 adult male rhesus monkeys (Macaca mulatta) by using MRI. Microdialysis cannulas-probes were implanted stereotactically in the brain, retrodialysis was performed to measure relative recovery, and a 1-h intravenous infusion of temozolomide was administered. Continuous microdialysis samples were collected from the pons and cortex over 4 h with concurrent serial plasma and CSF samples. Postsurgical verification of microdialysis cannula-probe placement was obtained via MRI in 3 macaques and by gross pathology in all 5 animals. The MRI-determined coordinates and surgical methodologies resulted in accurate microdialysis probe placement in the pons and cortex in 4 of the 5 macaques. Histologic examination from these 4 animals revealed negligible tissue damage to the pontine and cortical tissue from microdialysis. One macaque was maintained for 8 wk and had no deficits attributed to the procedure. This animal model allows for the determination of differences in CNS penetration of chemotherapeutic agents in the pons, cortex, and CSF after systemic drug administration. PMID- 24209973 TI - Adenocarcinoma of the ileocolic junction and multifocal hepatic sarcomas in an aged rhesus macaque (Macaca mulatta). AB - An aged male rhesus macaque in our colony had decreased appetite and a loss of interest in behavioral testing. CBC analysis revealed a regenerative, microcytic, hypochromic anemia with thrombocytosis, consistent with iron deficiency. A fecal occult blood test was positive. Ultrasound imaging revealed numerous, vascularized focal liver lesions that suggested metastases. The macaque's appetite continued to decrease, and he became more lethargic. At this point, the investigator elected to euthanize the macaque. At necropsy, the ileocolic junction was white and abnormally thickened, and the liver was pale tan with approximately 18 discrete white masses randomly scattered throughout the hepatic parenchyma. Histologically, the mass at the ileocolic junction was identified as an intestinal adenocarcinoma, whereas the liver masses were confirmed to be undifferentiated hepatic sarcomas. This case report describes a rhesus macaque that had 2 unrelated primary neoplasms. A review of the literature indicates that this rhesus macaque is the first reported to have an adenocarcinoma of the ileocolic junction and multiple hepatic sarcomas simultaneously. PMID- 24209974 TI - Brain abscess in a rhesus macaque (Macaca mulatta) with a cephalic implant. AB - We report a case of brain abscess after craniotomy and the placement of a recording chamber for electrophysiologic records in an adult rhesus macaque (Macaca mulatta) enrolled in visual research. Approximately 2 wk after surgery, the macaque presented with nonspecific gastrointestinal signs and showed no evidence of fever, neurologic deficits, increased intracranial pressure, suggestive alterations in the CBC, or abnormal changes in the recording chamber. The macaque responded to symptomatic and antibiotic treatment and showed no behavioral or abnormal clinical signs for 3 wk before collapsing suddenly. The macaque was euthanized, and pathologic evaluation revealed a large brain abscess immediately under the original craniotomy. PMID- 24209975 TI - Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts. AB - Some evidence suggests that genetic polymorphisms in oxytocin pathway genes influence various social behaviors, but findings thus far have been mixed. Many studies have been based in small samples and there is possibility of publication bias. Using data from 2 large U.S. prospective cohorts with over 11,000 individuals, we investigated 88 SNPs in OXTR, AVPR1A, and CD38, in relation to social integration (measured as social connectedness in both binary and continuous forms and being continuously married). After correction for multiple testing only one SNP in CD38 (rs12644506) was significantly associated with social integration and that SNP predicted when using a dichotomized indicator of social connectedness (adjusted p=0.02), but not a continuous measure of social connectedness or the continuously married outcome. A significant gender heterogeneous effect was identified in one OXTR SNP on dichotomized social connectedness; specifically, rs4686302 T allele was nominally associated with social connectedness in men, whereas the association direction was opposite in women (adjusted gender heterogeneity p=0.02). Furthermore, the rs53576 A allele was significantly associated with social connectedness only in women, and the effect magnitude was stronger in a dominant genetic model (adjusted p=0.003). In summary, our findings suggested that common genetic variants of OXTR, CD38, and AVPR1A are not associated with social integration as measured in this study using the simplified Berkman-Syme Social Network Index, but these findings and other work hint that effects may be modified by gender or other social experiences. Further work considering genetic pathways in relation to social integration may be more fruitful if these additional factors can be more comprehensively evaluated. PMID- 24209976 TI - Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells. AB - In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles. PMID- 24209977 TI - Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. AB - BACKGROUND: Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV) infection because of contraindications such as psychiatric illness, and a high burden of adverse events. We assessed the efficacy and safety of an interferon-free regimen--a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir (400 mg) and the HCV NS5A inhibitor ledipasvir (90 mg), with and without ribavirin--in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen. METHODS: For this open-label study, we enrolled 100 adult patients (>18 years) with HCV infection at a centre in the USA between Nov 2, 2012, and Dec 21, 2012. In cohort A, we used a computer-generated sequence to randomly assign (1:1:1; stratified by HCV genotype [1a vs 1b]) 60 non cirrhotic, treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks (group 1), sofosbuvir plus ledipasvir and ribavirin for 8 weeks (group 2), or sofosbuvir plus ledipasvir for 12 weeks (group 3). In cohort B, we randomly allocated (1:1; stratified by genotype and presence or absence of cirrhosis) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks (group 4) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks (group 5). 22 (55%) of 40 patients in cohort B had compensated cirrhosis. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01329978. FINDINGS: In cohort A, SVR12 was achieved by 19 (95%) of 20 patients (95% CI 75-100) in group 1, by 21 (100%) of 21 patients (84-100) in group 2, and by 18 (95%) of 19 patients (74-100) in group 3. In cohort B, SVR12 was achieved by 18 (95%) of 19 patients (74-100) in group 4 and by all 21 (100%) of 21 patients (84-100) in group 5. Two patients had viral relapse; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment. The most common adverse events were nausea, anaemia, upper respiratory tract infection, and headache. One patient in group five had a serious adverse event of anaemia, thought to be related to ribavirin treatment. INTERPRETATION: These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis. Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin. FUNDING: Gilead Sciences. PMID- 24209978 TI - Interferon-free hepatitis C treatment: one pill to fit all? PMID- 24209979 TI - Exploring productivity and collaboration in Australian Indigenous health research, 1995-2008. AB - BACKGROUND: Building research capacity in Indigenous health has been recognised as integral in efforts to reduce the significant health disparities between Indigenous and other Australian populations. The past few decades have seen substantial changes in funding policy for Australian Indigenous health research, including increases in overall expenditure and a greater focus on collaborative and priority-driven research. However, whether these policy shifts have resulted in any change to the structure of the research workforce in this field is unclear. We examine research publications in Australian Indigenous health from 1995-2008 to explore trends in publication output, key themes investigated, and research collaborations. METHODS: A comprehensive literature search was undertaken to identify research publications about Australian Indigenous health from 1995-2008. Abstracts of all publications identified were reviewed by two investigators for relevance. Eligible publications were classified according to key themes. Social network analyses of co-authorship patterns were used to examine collaboration in the periods 1995-1999, 2000-2004 and 2005-2008. RESULTS: Nine hundred and fifty three publications were identified. Over time, the number of publications per year increased, particularly after 2005, and there was a substantial increase in assessment of health service-related issues. Network analyses revealed a highly collaborative core group of authors responsible for the majority of outputs, in addition to a series of smaller separate groups. In the first two periods there was a small increase in the overall network size (from n = 583 to n = 642 authors) due to growth in collaborations around the core. In the last period, the network size increased considerably (n = 1,083), largely due to an increase in the number and size of separate groups. The general size of collaborations also increased in this period. CONCLUSIONS: In the past few decades there has been substantial development of the research workforce in Indigenous health, characterised by an increase in authors and outputs, a greater focus on some identified priority areas and sustained growth in collaborations. This has occurred in conjunction with significant changes to funding policy for Indigenous health research, suggesting that both productivity and collaboration may be sensitive to reform, including the provision of dedicated funding. PMID- 24209980 TI - Obsessive compulsive symptoms in patients with Schizophrenia on Clozapine and with Obsessive Compulsive disorder: a comparison study. AB - Obsessive compulsive symptoms are commonly reported in those with schizophrenia. Clozapine has previously been reported to induce, aggravate and alleviate these symptoms. It is unclear if these are similar to the symptoms experienced by those with obsessive compulsive disorder. This study describes the obsessive compulsive symptom profile of a population of patients with schizophrenia treated with clozapine (n = 62) and compares this with patients with Obsessive Compulsive Disorder (n = 35). All participants were attending an outpatient community mental health service. The Obsessive Compulsive Inventory (which measures the frequency and associated distress of a range of "behavioural" and "cognitive" symptoms), the Hospital Anxiety and Depression Scale and a demographic questionnaire were completed. In addition the schizophrenia group treated with clozapine completed the Brief Psychiatric Rating Scale. The OCD group reported significantly more symptoms for all OCI subscales compared to the clozapine group. Overall fourteen (22%) of the schizophrenia treated with clozapine group had clinically significant total OCI scores. Two (3%) had documented OCS pre clozapine. De novo OCS was reported in twelve (19%) cases. Nine (11%) had documented OC symptoms pre clozapine while only two (3%) had symptoms after clozapine was initiated. In terms of OC symptom profile, the clozapine group scored highest on the Doubting scale, a cognitive symptom whereas the OCD group scored highest on Washing, a behavioural symptom. Both groups reported greater distress with cognitive rather than behavioural symptoms. Medication including clozapine dose was not correlated with symptom severity. Anxiety correlated highly with obsessive compulsive symptoms in the Clozapine group but not the OCD group. Within the Clozapine group, Obsessing correlated highly with Unusual Thought Content. Findings suggest that obsessive compulsive symptoms in the Clozapine group may reflect a subtype of 'schizo-obsessive' disorder. PMID- 24209981 TI - An objective auditory measure to assess speech recognition in adult cochlear implant users. AB - OBJECTIVE: To verify if a mismatch negativity (MMN) paradigm based on speech syllables can differentiate between good and poorer cochlear implant (CI) users on a speech recognition task. METHODS: Twenty adults with a CI and 11 normal hearing adults participated in the study. Based on a speech recognition test, ten CI users were classified as good performers and ten as poor performers. We measured the MMN with /da/ as the standard stimulus and /ba/ and /ga/ as the deviants. Separate analyses were conducted on the amplitude and latency of the MMN. RESULTS: A MMN was evoked by both deviant stimuli in all normal hearing participants and in well performing CI users, with similar amplitudes for both groups. However, the amplitude of the MMN was significantly reduced for the poorer CI users compared to the normal hearing group and the good CI users. The latency was longer for both groups of cochlear implant users. A bivariate correlation showed a significant positive correlation between the speech recognition score and the amplitude of the MMN. CONCLUSIONS: The MMN can distinguish between CI users who have good versus poor speech recognition as assessed with conventional tasks. SIGNIFICANCE: Our findings suggest that the MMN can be use to assess speech recognition proficiency in CI users who cannot be tested with regular speech recognition tasks, like infants and other non-verbal populations. PMID- 24209982 TI - [Winged scapula caused by a long thoracic nerve lesion]. PMID- 24209983 TI - [Calcinosis cutis in adult patient with dermatomyositis]. PMID- 24209984 TI - Re-evaluation of glycerol utilization in Saccharomyces cerevisiae: characterization of an isolate that grows on glycerol without supporting supplements. AB - BACKGROUND: Glycerol has attracted attention as a carbon source for microbial production processes due to the large amounts of crude glycerol waste resulting from biodiesel production. The current knowledge about the genetics and physiology of glycerol uptake and catabolism in the versatile industrial biotechnology production host Saccharomyces cerevisiae has been mainly based on auxotrophic laboratory strains, and carried out in the presence of growth supporting supplements such as amino acids and nucleic bases. The latter may have resulted in ambiguous conclusions concerning glycerol growth in this species. The purpose of this study was to re-evaluate growth of S. cerevisiae in synthetic glycerol medium without the addition of supplements. RESULTS: Initial experiments showed that prototrophic versions of the laboratory strains CEN.PK, W303, and S288c did not exhibit any growth in synthetic glycerol medium without supporting supplements. However, a screening of 52 S. cerevisiae isolates for growth in the same medium revealed a high intraspecies diversity. Within this group significant variation with respect to the lag phase and maximum specific growth rate was observed. A haploid segregant of one good glycerol grower (CBS 6412-13A) was selected for detailed analysis. Single deletions of the genes encoding for the glycerol/H+ symporter (STL1), the glycerol kinase (GUT1), and the mitochondrial FAD+-dependent glycerol 3-phosphate dehydrogenase (GUT2) abolished glycerol growth in this strain, implying that it uses the same glycerol utilization pathway as previously identified in auxotrophic laboratory strains. Segregant analysis of a cross between CBS 6412-13A and CEN.PK113-1A revealed that the glycerol growth phenotype is a quantitative trait. Genetic linkage and reciprocal hemizygosity analysis demonstrated that GUT1CBS 6412-13A is one of the multiple genetic loci contributing to the glycerol growth phenotype. CONCLUSION: The S. cerevisiae intraspecies diversity with regard to glycerol growth is a valuable starting point to identify the genetic and molecular basis of this phenotype. This knowledge can be applied for further rational strain improvement with the goal of using glycerol as a carbon source in industrial biotechnology processes based on S. cerevisiae as a production organism. PMID- 24209985 TI - Medium-sized tandem repeats represent an abundant component of the Drosophila virilis genome. AB - BACKGROUND: Previously, we developed a simple method for carrying out a restriction enzyme analysis of eukaryotic DNA in silico, based on the known DNA sequences of the genomes. This method allows the user to calculate lengths of all DNA fragments that are formed after a whole genome is digested at the theoretical recognition sites of a given restriction enzyme. A comparison of the observed peaks in distribution diagrams with the results from DNA cleavage using several restriction enzymes performed in vitro have shown good correspondence between the theoretical and experimental data in several cases. Here, we applied this approach to the annotated genome of Drosophila virilis which is extremely rich in various repeats. RESULTS: Here we explored the combined approach to perform the restriction analysis of D. virilis DNA. This approach enabled to reveal three abundant medium-sized tandem repeats within the D. virilis genome. While the 225 bp repeats were revealed previously in intergenic non-transcribed spacers between ribosomal genes of D. virilis, two other families comprised of 154 bp and 172 bp repeats were not described. Tandem Repeats Finder search demonstrated that 154 bp and 172 bp units are organized in multiple clusters in the genome of D. virilis. Characteristically, only 154 bp repeats derived from Helitron transposon are transcribed. CONCLUSION: Using in silico digestion in combination with conventional restriction analysis and sequencing of repeated DNA fragments enabled us to isolate and characterize three highly abundant families of medium sized repeats present in the D. virilis genome. These repeats comprise a significant portion of the genome and may have important roles in genome function and structural integrity. Therefore, we demonstrated an approach which makes possible to investigate in detail the gross arrangement and expression of medium sized repeats basing on sequencing data even in the case of incompletely assembled and/or annotated genomes. PMID- 24209986 TI - [Interest of the cholinesterase assay during organophosphate poisonings]. AB - Cholinesterases are the main targets of organophosphorus compounds. The two enzymes present in the blood (butyrylcholinesterase, BChE; acetylcholinesterase, AChE) are biomarkers of their systemic toxicity. Activity of the plasma BChE is very often determined as it allows a rapid diagnostic of poisoning and is a marker of the persistence of the toxicant in the blood. The activity of the red blood cell AChE gives a better picture of the synaptic inhibition in the nervous system but the assay is less commonly available in routine laboratories. Better biomarker of the exposure, it allows a diagnosis of the severity of the poisoning and helps to assess the efficacy of oxime therapy. Besides the practical aspects of blood collection and sample processing, and the interpretation of the assays, this review stresses the complementarity of both enzyme assays and recalls their crucial interest for the confirmation of poisoning with an organophosphorus in a situation of war or terrorist attack and for the monitoring of occupational exposures. PMID- 24209987 TI - [A French regional network for management of severe trauma patients: the pelvic ring injury model]. PMID- 24209988 TI - Maintenance of unconsciousness with low plasma propofol concentrations in the neohepatic phase of liver transplantation using bispectral index-guided propofol anesthesia: a case report. AB - The authors present a case where a drug-effect parameter, the bispectral index, was used to guide propofol infusion when propofol-remifentanil anesthesia was used for liver transplantation. The target concentration of remifentanil was kept constant throughout the operation, and the bispectral index indicated that propofol infusion was not required during the anhepatic and neohepatic phases of the operation. The measured plasma propofol concentrations during the neohepatic phase were far below the usual values that are used to maintain anesthesia. However, the bispectral index indicated a state of unconsciousness. The patient regained consciousness rapidly several minutes after administration of neostigmine and cessation of remifentanil infusion. The measured plasma propofol concentrations were similar before and after recovery of consciousness. The possible mechanisms for the maintenance of anesthesia at reduced propofol concentrations are multifactorial and may be related to reduced liver function as well as an interaction between propofol and remifentanil or the use of a neuromuscular relaxant to suppress somatic afferent activity. PMID- 24209989 TI - [Anesthesia in spontaneous ventilation for difficult intubation]. AB - Difficult intubation in children is rare and often predictable during anesthesia consultation. This allows to establish a strategy to provide fiberoptic guided tracheal intubation with spontaneous ventilation in function of age and children pathology. A good knowledge of physiologic and anatomic children particularities, of fiberoptic technique and the respect for some principles lead to ensure the security of this procedure. First principle is to use only one anesthetic inhaled or intravenous agent in order to limit an important decrease of ventilation. The anesthetic technique recommended for pediatric fiberoptic guided intubation is inhaled anesthesia with sevoflurane. But it is possible to use an intravenous agent, like propofol, with a continuous infusion (bolus of 0.1 to 0.3 mg/kg then 0.1-0.3mg/kg per hour for maintenance) or with target controlled infusion (Schnider model, initial concentration 2.5 MUg/mL, then increase by 0.5 MUg/mL steps) particularly in children older than 5 years with an anesthetic depth control. Whatever the agent, the dose must to be titrated to maintain spontaneous ventilation. Second principle is to combine an airway local anesthesia with general anesthesia to limit airway reactivity. First, a nose topical anesthesia is administered with lidocaine plus naphazoline in children older than 2 years. Then, a laryngeal topical anesthesia is realized with lidocaine 1% (1-2 mL, 2mg/kg) through operating channel of fiberoptic bronchoscope. Finally, third principle is to ensure patient oxygenation with several techniques like use of endoscopic facial mask or nasopharyngeal tube. The use of laryngeal mask is a rescue technique in case of spontaneous ventilation lost. In conclusion, each institution has to establish an algorithm with his own knowledge, constantly feasible and regularly taught. PMID- 24209990 TI - [Ambulatory surgery in France: practical and medicolegal considerations]. AB - In France, ambulatory anaesthesia and surgery seem to be well codified. Many recommendations have been published by the Health Authority and the professional associations: they are summarized in this review. However, numerous practical problems persist: for example, two situations specific to paediatric practice are problematic parental comprehension and application of the information provided and poor access to strong analgesics outside the hospital. Despite this, the paediatric population is an ideal target for ambulatory care because of its usual good health and quicker recovery after minor injury as proven by the small percentage of failure and readmission. PMID- 24209991 TI - [The choice of a pediatric anesthesia ventilator]. AB - The technology of anesthesia ventilators has substantially progressed during last years. The choice of a pediatric anesthesia ventilator needs to be led by multiple parameters: requirement, technical (pneumatic performance, velocity of halogenated or oxygen delivery), cost (purchase, in operation, preventive and curative maintenance), reliability, ergonomy, upgradability, and compatibility. The demonstration of the interest of pressure support mode during maintenance of spontaneous ventilation anesthesia makes this mode essential in pediatrics. In contrast, the financial impact of target controlled inhalation of halogenated has not be studied in pediatrics. Paradoxically, complex and various available technologies had not been much prospectively studied. Anesthesia ventilators performances in pediatrics need to be clarified in further clinical and bench test studies. PMID- 24209993 TI - Diffuse large B-cell lymphoma of the sinonasal tract: analysis of survival in 852 cases. AB - PURPOSE: Diffuse large B-cell lymphomas (DLBCLs) are rare tumors of the head and neck that often have non-specific presentations and significant morbidity and mortality. In this analysis we use a large cohort to compare the demographic and disease-specific parameters affecting survival and incidence of DLBCLs. METHODS: The United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry was utilized to extract data regarding sinonasal diffuse large B-cell lymphoma between 1973 and 2009. A total of 852 cases of sinonasal DLBCLs were found. Presenting symptoms, demographics, disease specific survival, relative survival and survival by treatment modality were described for this rare tumor. RESULTS: Overall disease specific survival (DSS) at 1-year was 84.7% and at 5 years was 68.0%. DSS was significantly lower for those not treated with radiation therapy, with 1- and 5-year survival rates of 77.3% and 62.5%, versus those treated with radiation therapy, with 1- and 5-year rates of 89.2% and 71.5% (p<0.05). Prognosis was significantly better for patients treated with radiation therapy (HR 0.6, p<0.05) while it was poorer for patients with involvement of multiple sinuses (HR 1.5, 1.8, p<0.05). CONCLUSIONS: DLBCLs of the sinonasal tract are rare tumors of the head and neck. Survival is significantly improved for those treated with radiation therapy while the involvement of multiple sinuses is a negative prognostic indicator. PMID- 24209992 TI - Racial disparities in Human Papillomavirus (HPV) associated head and neck cancer. AB - PURPOSE: Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use. MATERIALS AND METHODS: 385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients' demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox's proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV positivity, respectively. RESULTS: HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05-0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42-4.59) decreased to almost unity (HR 1.49, 95% CI 0.75-2.93) after adjustment for HPV and smoking. CONCLUSIONS: Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC. PMID- 24209994 TI - Does previous pelvic surgery hasten the onset of clinically bothersome urodynamic stress incontinence? AB - OBJECTIVE: To study the impact of previous pelvic surgery on the onset of clinically bothersome urodynamic stress incontinence (USI). STUDY DESIGN: Retrospective case-cohort study at a District General Hospital of 305 women undergoing surgery for urodynamic stress incontinence: case note and computer records review of patients undergoing USI surgery. The main outcome measures were age at index USI surgery, and duration from previous pelvic surgery to index surgery. RESULTS: 305 women were included, of whom 118 had previous pelvic surgery including abdominal hysterectomy (TAH) (n=74), vaginal hysterectomy (n=23), anterior colporrhaphy (n=27) and posterior colporrhaphy (n=25). The mean age in the previous surgery group was 62.4 years (95% CI 60.2-64.6, range 32-87) and 53.2 years in the no previous surgery group (95% CI 51.4-55, range 30-88). There were no differences in the mean BMI (28.4 vs. 27.5), or mean parity (2.4 vs. 2.5). The median duration from previous surgery to the index USI surgery was 222 months (abdominal hysterectomy), 96 months (vaginal hysterectomy), 78 months (anterior colporrhaphy), and 72 months (posterior colporrhaphy). CONCLUSION: Previous pelvic surgery does not seem to accelerate the onset of USI, as women without previous pelvic surgery presented at a significantly earlier age (53.2 years) with clinically bothersome USI than those who had previous surgery (62.4 years). Posterior colporrhaphy had the shortest interval to index USI surgery amongst previous operations. PMID- 24209996 TI - "Mustache sign" due to Stensen duct dilation. AB - An 80-year-old woman presented with a 5-year history of painless swellings of the left and right cheeks. The degree of swelling did not change with mastication. On palpation, the cheeks were soft, well defined, and movable. Compression and massage of the swollen areas caused increased salivary discharge from the orifices of the Stensen ducts. Three-dimensional computed tomography showed well bordered, 15- to 20-mm wide, bilateral, tube-like dilatations of the ducts. The ductal origin of the swellings was explained to the patient, but she refused invasive procedures, thus no sialogram or surgical procedure was performed. We describe the clinical and radiographic features of a case of bilateral, congenital Stensen duct dilatation with bilateral swelling of the cheeks. PMID- 24209995 TI - Quantitative diagnosis of salivary gland tumors with contrast-enhanced ultrasound -a preliminary study. AB - OBJECTIVE: To quantitatively analyze the value of qualitative diagnosis of salivary gland masses with contrast-enhanced ultrasound (CEUS). STUDY DESIGN: The enhanced sonographic features of 68 salivary gland masses were analyzed to differentiate them. The final diagnoses were confirmed by biopsy pathology. RESULTS: We observed from the perfusion kinetics of CEUS that most pleomorphic adenomas manifested lower enhancement and well-defined margins; most Warthin tumors presented with higher enhancement and well-defined margins; and most malignant tumors had higher enhancement and poorly defined margins. Their time intensity curves showed pleomorphic adenomas were hypovascularized with a poor perfusion, whereas Warthin tumors and malignant tumors were hypervascularized with a rich perfusion. Additionally, malignant tumors showed significantly shortened time to peak and richer maximum signal intensity compared with Warthin tumors. CONCLUSIONS: The features of salivary gland masses identified with CEUS were helpful in the differential diagnosis of salivary gland masses. PMID- 24209997 TI - Identification of peripheral vessels in oral and maxillofacial regions on magnetic resonance angiography obtained using a balanced steady-state free precession sequence with a time-spatial labeling inversion pulse and using fresh blood imaging. AB - OBJECTIVE: To elucidate the characteristics of visualizing thin main peripheral vessels in oral and maxillofacial regions of 3-dimensional magnetic resonance angiography (MRA) using a balanced steady-state free-precession (SSFP) sequence with a time-spatial labeling inversion pulse (time-SLIP) and using fresh blood imaging (FBI). STUDY DESIGN: The conspicuity of blood vessels and the characteristics on MRA using SSFP with a time-SLIP was compared with those on MRA using FBI in 20 healthy participants. RESULTS: The conspicuity of the main peripheral arteries was significantly higher on MRA using SSFP with a time-SLIP than on MRA using FBI. MRA scans using SSFP were obtained in all participants, and scans using FBI were obtained in 16 of 20 participants. An electrocardiogram was unnecessary when using SSFP but was necessary when using FBI. CONCLUSIONS: MRA obtained using SSFP with a time-SLIP is a useful technique to visualize thin main peripheral arteries in the oral and maxillofacial regions without contrast medium. PMID- 24209998 TI - Wnt signaling in triple negative breast cancer is associated with metastasis. AB - BACKGROUND: Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies. METHODS: We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease. RESULTS: The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/beta-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/beta catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or beta-catenin (functional read out of Wnt/beta-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from beta-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/beta-catenin classifier had a greater risk of lung and brain, but not bone metastases. CONCLUSION: These data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways. PMID- 24209999 TI - Antidepressant-like effect of ascorbic acid is associated with the modulation of mammalian target of rapamycin pathway. AB - The present study investigated the involvement of the PI3K, GSK-3beta, heme oxygenase-1 (HO-1) and mTOR in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST). Male Swiss mice were pretreated with ascorbic acid (1 mg/kg, p.o.) or vehicle and 45 min after, LY294002 (10 MUg/site, i.c.v., reversible PI3K inhibitor), rapamycin (0.2 nmol/site, i.c.v., selective mTOR inhibitor), zinc protoporphyrin (ZnPP - 10 ng/site, i.c.v., HO-1 inhibitor) or vehicle was administered. We also investigated the synergistic effect of ascorbic acid (0.1 mg/kg, p.o., sub-effective dose in the TST) with lithium chloride (10 mg/kg, p.o., non-selective GSK-3beta inhibitor), AR-A014418 (0.01 MUg/site, i.c.v., selective GSK-3beta inhibitor) or cobalt protoporphyrin (CoPP - 0.01 MUg/site, i.c.v., HO-1 inducer) in the TST. The antidepressant-like effect of ascorbic acid (1 mg/kg, p.o.) was prevented by the treatment of mice with LY294002, rapamycin or ZnPP. In addition, sub-effective doses of lithium chloride, AR-A014418 or CoPP, combined with a sub-effective dose of ascorbic acid produced a synergistic antidepressant-like effect. We also demonstrated that 1 h after its administration, ascorbic acid increased the phosphorylation of p70S6K and the immunocontent of PSD-95 in the hippocampus of mice. These results indicate that the antidepressant-like effect of ascorbic acid in the TST might be dependent on the activation of PI3K and mTOR, inhibition of GSK-3beta as well as induction of HO-1, reinforcing the notion that these are important targets for antidepressant activity and contributing to better elucidate the mechanisms underlying the antidepressant-like effect of ascorbic acid. PMID- 24210000 TI - Is copper chelation an effective anti-angiogenic strategy for cancer treatment? AB - Angiogenesis and the acquisition of an angiogenic phenotype is important for cancer cell proliferation. Copper in an essential trace element that participates in many enzymatic complexes like the cytochrome c, superoxide dismutase and lysyl oxidase and it is involved in processes, like embryogenesis, growth, angiogenesis and carcinogenesis. In particular, its involvement in carcinogenesis was described for the first time in oral submucous fibrosis, where fibroblasts produce large amounts of collagen in the presence of copper. Copper's action in carcinogenesis is two-fold: (1) it participates in reactions with an increased redox potential that result in the production of oxidative products and oxidative stress. Through this mechanism, copper may cause DNA mutations in the nucleus and mitochondria or alterations to membrane phospholipids, (2) it participates in angiogenesis even in the absence of angiogenic molecules, as it was reported for the first time in rabbit cornea models with copolymer pellets charged with PGE1. Copper chelation regimens like penicillamine and tetrathiomolybdate are being described in the literature as having anti-angiogenic, anti-fibrotic and anti inflammatory actions. Animal models of brain cancer that evaluated the anti angiogenic properties of copper, have proven evidence of the reduction of tumor's microvascular supply, tumor volume and vascular permeability after plasma copper levels reduction. Interestingly, plasma copper levels reduction was shown to suppress micrometastases generation in mice models of breast cancer. We hypothesize that copper chelation therapy: increases oxidative stress in cancer cells to a level that does not allow survival because of the reduction of anti oxidative enzymes production. It may also result in inhibition of angiogenesis and of the initiation of the angiogenic switch, because copper normally enhances endothelial cell migration and proliferation, improves binding of growth factors to endothelial cells and enhances the expression of angiogenic molecules. Copper chelation may also reduce extracellular matrix degradation and cancer spread, through reduction of MMP-9 production and probably of other collagenases and may inhibit propagation of micrometastases. However, copper chelation therapy may enhance angiogenesis through reduction of thrombospondin-1, that results into an increase in VEGF-VEGFR2 complexes and a high level of active MMP-9. These hypotheses help in understanding of the anti-angiogenic action of copper chelation therapies and of the complex network of interactions between copper and other molecules involved in angiogenesis. It may also stimulate further research regarding differences in copper metabolism, the effects of anti-copper regimens on organs, the development of resistance, and their possible angiogenic action through thrombospondin expression reduction. PMID- 24210001 TI - Curing baldness activates antibiotic production. AB - Kalan and colleagues describe an unusual way of activating a "silent" gene cluster for the biosynthesis of a new antibiotic by analyzing and curing the aerial growth defect of an old Streptomyces isolate, Streptomyces calvus. This commentary addresses the broad scientific and historical context and practical and biological significance of this finding. PMID- 24210002 TI - Urea transporter inhibitors: en route to new diuretics. AB - A selective urea transporter UT-A1 inhibitor would be a novel type of diuretic, likely with less undesirable side effects than conventional diuretics, because it acts on the last portion of the nephron. In this issue of Chemistry & Biology, Esteva-Font and colleagues develop such an inhibitor by using a clever high throughput screening assay and document its selectivity. PMID- 24210003 TI - A jack of all trades to combat drug-resistant Gram-negative bacteria. AB - In this issue of Chemistry & Biology, Jahnsen and colleagues describe a multimodal mechanism of action of an unusual peptide-peptoid hybrid with broad spectrum antibacterial activity. They demonstrate that the molecule has effects on many aspects of bacterial metabolism and also modulates host immune responses. PMID- 24210004 TI - Bridging the spectral gap in fluorescent proteins through directed evolution. AB - Fluorescent proteins are used as noninvasive tags for protein trafficking, structure, and action. In this issue of Chemistry & Biology, Hoi and colleagues present a new optimized zFP538 yellow fluorescent protein called mPapaya1 that is bright, monomeric, and an excellent fusion partner for cellular proteins. PMID- 24210005 TI - Finding epitopes with computers. AB - The goal of structural vaccinology is to enable the design and engineering of improved antigens. In a recent issue of Chemistry & Biology, Gourlay and colleagues provided evidence that structure-based computational methods allow prediction of B cell epitopes, a crucial step for antigen selection and optimization in vaccine development. PMID- 24210006 TI - Site-specific differences in proteasome-dependent degradation of monoubiquitinated alpha-synuclein. AB - The formation of toxic aggregates composed largely of the protein alpha-synuclein are a hallmark of Parkinson's disease. Evidence from both early-onset forms of the disease in humans and animal models has shown that the progression of the disease is correlated with the expression levels of alpha-synuclein, suggesting that cellular mechanisms that degrade excess alpha-synuclein are key. We and others have shown that monoubiquitinated alpha-synuclein can be degraded by the 26S proteasome; however, the contributions of each of the nine known individual monoubiquitination sites were unknown. Herein, we determined the consequences of each of the modification sites using homogenous, semisynthetic proteins in combination with an in vitro proteasome turnover assay. The data suggest that the site-specific effects of monoubiquitination support different levels of alpha synuclein degradation. PMID- 24210008 TI - Biogeochemical characterization of MC252 oil:sand aggregates on a coastal headland beach. AB - MC252 oil:sand aggregates, termed surface residue balls (SRBs), were sampled for physical, chemical and microbial characteristics from different tidal zones on a coastal headland beach in Louisiana, USA. Supratidal SRBs were smaller, had low moisture content, and salinities that were <2 ppt. Intertidal SRBs were hypersaline and had higher N and sulfate concentrations, consistent with regular tidal inundation. Crude oil components were highest in the intertidal "oil mat" SRBs with C1- and C2-phenanthrenes, C2- and C3-dibenzothiophenes comprising the majority of the PAH concentrations. In the other SRB categories, PAHs and alkanes were depleted and profiles were skewed toward higher molecular weight compounds. Oxygen microelectrode measurements demonstrated that saturated O2 is present immediately after wetting, but O2 consumption in the interior of the aggregate occurs after a few days. Microbial populations varied with position on the beach but sequences similar to known PAH-degrading taxa (Mycobacterium sp. and Stenotrophomonas sp.) were observed. PMID- 24210009 TI - Natural antifouling compounds produced by a novel fungus Aureobasidium pullulans HN isolated from marine biofilm. AB - A fungus, Aureobasidium pullulans, was isolated from marine biofilm and identified. A bioassay-guided fractionation procedure was developed to isolate and purify antifouling compounds from A. pullulans HN. The procedure was: fermentation broth-aeration and addition of sodium thiosulfate-graduated pH and liquid-liquid extraction-SPE purification-GC-MS analysis. Firstly, the fermentation broth was tested for its toxicity. Then it was treated with aeration and addition of sodium thiosulfate, and its toxicity was almost not changed. Lastly, antifouling compounds were extracted at different pH, the extract had high toxicity at pH 2 but almost no toxicity at pH 10, which suggested the toxicants should be fatty acids. The EC50 of the extract against Skeletonema costatum was 90.9 MUg ml(-1), and its LC50 against Balanus amphitrete larvae was 22.2 MUg ml(-1). After purified by HLB SPE column, the EC50 of the extract against S. costatum was 49.4 MUg ml(-1). The myristic and palmitic acids were found as the main toxicants by GC-MS. PMID- 24210010 TI - Merchant ships discharging unwanted marine species in close proximity of a French aquaculture area: risks involved. AB - The most important oyster farming area in Europe is in a close proximity of two medium size merchant ports. Cargo ships deballast in this area before loading, releasing unwanted or noxious marine species. During a sampling campaign aboard these arriving ships, we found in some ballast water samples a huge number of potentially toxic dinoflagellates and some potentially pathogenic bacteria. A model was applied to find the potential geographical spread of the discharged ballast water. This model predicts the water to reach highly vulnerable shellfish farmed areas in six to eight days. PMID- 24210011 TI - Bioavailability of trace elements in surface sediments from Kongsfjorden, Svalbard. AB - The bioavailability of trace elements in marine sediments from Kongsfjorden (Svalbard Islands, Norwegian Arctic) was assessed and discussed. Total concentrations of several elements were determined in two granulometric fractions and their bioavailability evaluated by both applying a sequential-selective extraction procedure and using a biomimetic approach based on proteolytic enzymes. Total concentration values and solid speciation patterns indicated overall that the anthropogenic impact of trace elements in the investigated area is negligible, although a minor enrichment with respect to crustal values was found for As, Cd, Cr, Ni, and V. Enrichment of trace elements in the <63-MUm fraction compared to the coarser one was evident for As, Cd, Cr, and Ni. The evaluation of the bioavailable fractions showed that a large part of the total content of trace elements cannot enter the aquatic food chain and emphasised the risk of overestimating the environmental impact of heavy metals if the assessment is only based on total concentrations. PMID- 24210012 TI - Pulmonary nontuberculous mycobacterial disease, Ontario, Canada, 1998-2010. AB - We measured the prevalence and temporal trends of pulmonary nontuberculous mycobacterial disease among residents of Ontario, Canada, during 1998-2010. Five year prevalence increased from 29.3 cases/100,000 persons in 1998-2002 to 41.3/100,000 in 2006-2010 (p<0.0001). Improved laboratory methods did not explain this increase, suggesting a surge in disease prevalence. PMID- 24210013 TI - Theory-based training strategies for modifying practitioner concerns about exposure therapy. AB - Despite the well-established efficacy of exposure therapy in the treatment of pathological anxiety, many therapists believe this treatment carries an unacceptably high risk for harm, is intolerable for patients, and poses a number of ethical quandaries. These beliefs have been shown to account for two related problems: (a) underutilization of exposure therapy, and (b) overly cautious and suboptimal delivery the treatment, which likely attenuates treatment outcomes. At present, there is little guidance for those who train exposure therapists to address these concerns. This article reviews therapist negative beliefs about exposure therapy and discusses their modification based on findings from social and cognitive psychology pertinent to belief change, including dual-processing in reasoning, the need for cognition and affect, and attitude inoculation. A number of strategies are offered for augmenting training in exposure therapy in order to promote positive beliefs about the treatment. These strategies involve: (a) therapists engaging in simulated exposure therapy exercises and presenting arguments in defense of exposure's safety, tolerability, and ethicality, and (b) training therapists using emotion-based appeals (e.g., case examples) to supplement research findings. Directions for future research on practitioner concerns about exposure therapy are discussed. PMID- 24210014 TI - The hidden cost of housing practices: using noninvasive imaging to quantify the metabolic demands of chronic cold stress of laboratory mice. AB - Laboratory mice routinely are housed at 20 to 22 degrees C-well below the murine thermoneutral zone of 29 to 34 degrees C. Chronic cold stress requires greater energy expenditure to maintain core body temperature and can lead to the failure of mouse models to emulate human physiology. We hypothesized that mice housed at ambient temperatures of 20 to 22 degrees C are chronically cold-stressed, have greater energy expenditure, and have high glucose utilization in brown adipose tissue. To test our hypotheses, we used indirect calorimetry to measure energy expenditure and substrate utilization in C57BL/6J and Crl:NU-Foxn1(nu) nude mice at routine vivarium (21 degrees C), intermediate (26 degrees C), and heated (31 degrees C) housing temperatures. We also examined the activation of interscapular brown adipose tissue, the primary site of nonshivering thermogenesis, via thermography and glucose uptake in this region by using positron emission tomography. Energy expenditure of mice was significantly higher at routine vivarium temperatures compared with intermediate and heated temperatures and was associated with a shift in metabolism toward glucose utilization. Brown adipose tissue showed significant activation at routine vivarium and intermediate temperatures in both hirsuite and nude mice. Crl:NU Foxn1(nu) mice experienced greater cold stress than did C57BL/6J mice. Our data indicate mice housed under routine vivarium conditions are chronically cold stress. This novel use of thermography can measure cold stress in laboratory mice housed in vivaria, a key advantage over classic metabolic measurement tools. Therefore, thermography is an ideal tool to evaluate novel husbandry practices designed to alleviate murine cold stress. PMID- 24210015 TI - Surgical methods for full-thickness skin grafts to induce alopecia areata in C3H/HeJ mice. AB - Alopecia areata is a cell-mediated autoimmune disease of humans and many domestic and laboratory animal species. C3H/HeJ inbred mice spontaneously develop alopecia areata at a low frequency (approximately 20% by 12 mo of age). Transferring full thickness skin grafts from affected, older mice to young mice of the same strain reliably reproduces alopecia areata, thus enabling investigators to study disease pathogenesis or intervention with a variety of therapeutic approaches. We here describe in detail how to perform full-thickness skin grafts and the follow-up procedures necessary to consistently generate mice with alopecia areata. These engrafted mice can be used to study the pathogenesis of cell-mediated autoimmune disease and for drug-efficacy trials. This standard protocol can be used for many other purposes when studying abnormal skin phenotypes in laboratory mice. PMID- 24210016 TI - Development of a murine model of blunt hepatic trauma. AB - Despite the prevalence of blunt hepatic trauma in humans, there are few rodent models of blunt trauma that can be used to study the associated inflammatory responses. We present a mouse model of blunt hepatic trauma that was created by using a cortical contusion device. Male mice were anesthetized with ketamine xylazine-buprenorphine and placed in left lateral recumbency. A position of 2 mm ventral to the posterior axillary line and 5 mm caudal to the costal margin on the right side was targeted for impact. An impact velocity of 6 m/s and a piston depth of 12 mm produced a consistent pattern of hepatic injury with low mortality. All mice that recovered from anesthesia survived without complication for the length of the study. Mice were euthanized at various time points (n = 5 per group) until 7 d after injury for gross examination and collection of blood and peritoneal lavage fluids. Some mice were reanesthetized for serial monitoring of hepatic lesions via MRI. At 2 h after trauma, mice consistently displayed laceration, hematoma, and discoloration of the right lateral and caudate liver lobes, with intraabdominal hemorrhage but no other gross injuries. Blood and peritoneal lavage fluid were collected from all mice for cytokine analysis. At 2 h after trauma, there were significant increases in plasma IL10 as well as peritoneal lavage fluid IL6 and CXCL1/KC; however, these levels decreased within 24 h. At 7 d after trauma, the mice had regained body weight, and the hepatic lesions, which initially had increased in size during the first 48 h, had returned to their original size. In summary, this technique produced a reliable, low mortality, murine model that recreates features of blunt abdominal liver injury in human subjects with similar acute inflammatory response. PMID- 24210017 TI - Surgical anatomy, transperitoneal approach, and early postoperative complications of a ventral lumbar spine surgical model in Lewis rats. AB - Surgical models in animals are used extensively to study small molecules and devices for lumbar intervertebral disc repair, replacement, and fusion. Although the ventral lumbar animal models themselves are well described, critical assessment of morbidity and mortality avoidance when using the models have not been reported. Hypothesizing that technique modifications and the relative prevalence and severity of complications would be correlated, we collected and examined peri- and postoperative data stratified by surgical technique. We here report complications associated with the transperitoneal approach to the lumbar spine in 268 Lewis rats and offer data-driven suggestions regarding complication avoidance through technique modification. Compared with wider exposure, limiting the width of exposure to a maximum of 3 mm resulted in fewer neurologic complications in the lower limbs. In addition, avoiding extracorporeal reflection of the small intestine during the exposure was associated with lower incidence of postoperative gastrointestinal distress and fewer situations requiring euthanasia. These findings underscore the importance of detailed approaches in minimizing postoperative morbidity and attrition in surgical models. PMID- 24210018 TI - Stage of the estrous cycle does not influence myocardial ischemia-reperfusion injury in rats (Rattus norvegicus). AB - Even though cardiovascular disease is the leading cause of death for men and women, the vast majority of animal studies use male animals. Because female reproductive hormones have been associated with cardioprotective states, many investigators avoid using female animals because these hormones are cyclical and may introduce experimental variability. In addition, no studies have investigated the specific effects of the estrous cycle on cardiac ischemic injury. This study was conducted to determine whether the estrous cycle stage influences the susceptibility to ischemic injury in rat hearts. Estrous cycle stage was determined by using vaginal smear cytology, after which hearts underwent either in vivo (surgical) or ex vivo (isolated) ischemia-reperfusion injury. For in vivo studies, the left anterior coronary artery was ligated for 25 min of ischemia and subsequently released for 120 min of reperfusion. Infarct sizes were 42% +/- 6%; 49% +/- 4%; 40% +/- 9%; 47% +/- 9% of the zone-at-risk for rats in proestrus, estrus, metestrus, and diestrus, respectively. For ex vivo studies, isolated, perfused hearts underwent global ischemia and reperfusion for 25 and 120 min, respectively. Similar to our in vivo studies, the ex vivo rat model showed no significant differences in susceptibility to infarction or extent of cardiac arrhythmia according to estrous stage. To our knowledge, these studies provide the first direct evidence that the stage of estrous cycle does not significantly alter cardiac ischemia-reperfusion injury in rats. PMID- 24210019 TI - Experimental infection of New Zealand white rabbits (Oryctolagus cuniculi) with Leporid herpesvirus 4. AB - Leporid herpesvirus 4 (LHV4) is a novel alphaherpesvirus recently identified in domestic rabbits (Oryctolagus cuniculi). Little is known about the pathogenesis or time course of disease induced by this virus. We therefore intranasally inoculated 22 female New Zealand white rabbits with 8.4 * 10(4) CCID50 of a clinical viral isolate. Rabbits were monitored for clinical signs, viral shedding in oculonasal secretions, and development and persistence of serum antibodies. Rabbits were euthanized at 3, 5, 7, 14, and 22 d postinfection (dpi) to evaluate gross and microscopic changes. Clinical signs were apparent between 3 to 8 dpi, and included oculonasal discharge, respiratory distress, and reduced appetite, and viral shedding occurred between 2 and 8 dpi. Seroconversion was seen at 11 dpi and persisted to the end of the study (day 22). Severe necrohemorrhagic bronchopneumonia and marked pulmonary edema were noted by 5 dpi and were most severe at 7 dpi. Pulmonary changes largely resolved by 22 dpi. In addition, multifocal splenic necrosis was present at 5 dpi and progressed to submassive necrosis by 7 dpi. Eosinophilic herpesviral intranuclear inclusion bodies were detected in the nasal mucosa, skin, spleen, and lung between 3 to 14 dpi. LHV4 is a pathogen that should be considered for rabbits that present with acute respiratory disease. LHV4 infection can be diagnosed based on characteristic microscopic changes in the lungs and spleen and by virus isolation. Serum antibody levels may be used to monitor viral prevalence in colonies. PMID- 24210020 TI - Assessing the pulsatility of luteinizing hormone in female vervet monkeys (Chlorocebus aethiops sabaeus). AB - Specific alterations in the pulsatility of luteinizing hormone (LH) are linked to obesity-related subfertility in ovulatory women. Vervet monkeys (Chlorocebus aethiops sabaeus) are an Old World nonhuman primate that develops obesity and has a menstrual cycle similar to humans. We evaluated follicular-phase LH pulses in 12 adult normal-weight female vervets. Serum was collected every 10 min for 4 h by using a tether device in conscious, freely moving monkeys on menstrual cycle days 2 through 5. Serum estradiol was collected daily during the follicular phase to identify the luteal-follicular transition. For comparison, we used data from 12 ovulatory normal-weight women who had undergone frequent blood sampling of early-follicular LH. LH pulse frequency was similar, with 2.8 +/- 0.7 LH pulses during 4 h in vervets compared with 2.3 +/- 0.7 LH pulses during 4 h in women. The LH pulse mass (percentage change in the pulse peak over the preceding nadir) was 123.2% +/- 27.4% in vervets and 60.9% +/- 14.9% in humans. The first day of low serum estradiol after the follicular-phase peak was denoted as the day of the luteal-follicular transition. Luteectomy was performed on luteal days 7 through 9, and corpora lutea were confirmed by histology. We demonstrate that follicular LH patterns in vervets are similar to those in humans and that the luteal phase is easily identified by monitoring daily serum estradiol. These findings demonstrate that vervet monkeys are a suitable animal model for evaluating LH pulse dynamics longitudinally in studies of diet-induced obesity. PMID- 24210021 TI - An outbreak of Yersinia enterocolitica in a captive colony of African green monkeys (Chlorocebus aethiops sabaeus) in the Caribbean. AB - Yersinia enterocolitica is a zoonotic gram-negative pathogen that causes mesenteric lymphadenitis, terminal ileitis, acute gastroenteritis, and septicemia in domestic animals and primates. In 2012, 46 captive African green monkeys (Chlorocebus aethiops sabaeus) died during an outbreak of acutely fatal enteric disease over a period of 1 mo on the island of St Kitts. The affected monkeys presented with a history of mucohemorrhagic diarrhea, marked dehydration, and depression. Fifteen bacterial isolates were recovered from the spleen, liver, and lungs of affected monkeys. All isolates were identified as Y. enterocolitica by biochemical analysis and sequence comparison of the 16S rRNA gene. Phenotypic and genotypic analysis of the recovered isolates revealed homogeneity among the recovered bacteria, and all isolates gave a random amplified polymorphic DNA pattern resembling that given by genotype D under serotypes O:7,8. This outbreak represents the first isolation and characterization of Y. enterocolitica as the causative agent of fatal enteric disease in primates in the Caribbean. PMID- 24210022 TI - Generalized seizure activity in an adult rhesus macaque (Macaca mulatta) during ketamine anesthesia and urodynamic studies. AB - We report a case of a generalized seizure in an adult female rhesus macaque ( Macaca mulatta) undergoing a urodynamic evaluation while she was anesthetized with continuous-infusion ketamine. The seizure presented with generalized tonic clonic activity during bladder infusion with saline. The tonic-clonic phase was self-limited and was followed by focal facial twitching, which was interrupted by bolus administration of intravenous diazepam. The ictal event was documented as pressure oscillations during cystometrogram recordings and a period of external urethral sphincter muscle activation, which was detectable by electromyography. An acute decrease in urethral pressure was demonstrated at the end of the generalized seizures. Ketamine anesthesia combined with relatively rapid infusion of saline into the bladder may have contributed to the onset of seizures. In addition, this case highlights the value of having a fast-acting benzodiazepine agent available to stop continuous or residual seizure activity during diagnostic or experimental procedures in anesthetized nonhuman primates. PMID- 24210023 TI - Metastatic hepatocellular carcinoma in a juvenile rhesus macaque (Macaca mulatta). AB - Neoplasia in juvenile (younger than 5 y) rhesus macaques has been estimated to represent only approximately 1.4% of all occurrences of spontaneous neoplasia. Here we report an unusual case of a 3.75-y-old primiparous female rhesus macaque that was euthanized due to poor prognosis associated with progressive anemia, marked hepatomegaly, and radiographic evidence of meta- static neoplasia. Postmortem examination revealed an invasive, hemorrhagic hepatic mass that effaced approximately 70% of the liver parenchyma and had evidence of metastatic spread to multiple abdominal organs, the lungs, and the pituitary gland. Neoplastic polygonal cells lined large necrohemorrhagic cavities and exhibited marked anisocytosis and anisokaryosis, with frequent multinucleate cells. There was no desmoplasia associated with the primary neoplasm or metastases. Immunohistochemical studies revealed the neoplastic cells to be diffusely reactive with pancytokeratin, cytokeratin 7, and cytokeratin 8/18 antibodies and rarely reactive with carcinoembryonic antigen antibodies. The cells did not react with vimentin, S100, CD31, or factor VIII antibodies. Tumor morphology and immunophenotype led to the diagnosis of anaplastic hepatocellular carcinoma. This report represents the first known case of metastatic liver neoplasia in a rhesus macaque. The young age of this animal and the aggressive nature of the neoplasm are highly unusual and reminiscent of adolescent onset hepatocellular carcinoma in humans. PMID- 24210024 TI - The detection of T-wave variation linked to arrhythmic risk: an industry perspective. AB - Although the scientific literature contains ample descriptions of peculiar patterns of repolarization linked to arrhythmic risk, the objective quantification and classification of these patterns continues to be a challenge that impacts their widespread adoption in clinical practice. To advance the science, computerized algorithms spawned in the academic environment have been essential in order to find, extract and measure these patterns. However, outside the strict control of a core lab, these algorithms are exposed to poor quality signals and need to be effective in the presence of different forms of noise that can either obscure or mimic the T-wave variation (TWV) of interest. To provide a practical solution that can be verified and validated for the market, important tradeoffs need to be made that are based on an intimate understanding of the end user as well as the key characteristics of either the signal or the noise that can be used by the signal processing engineer to best differentiate them. To illustrate this, two contemporary medical devices used for quantifying T-wave variation are presented, including the modified moving average (MMA) for the detection of T-wave Alternans (TWA) and the quantification of T-wave shape as inputs to the Morphology Combination Score (MCS) for the trending of drug-induced repolarization abnormalities. PMID- 24210050 TI - "Who'll be the next in line?" The lung allocation score in patients with pulmonary arterial hypertension. PMID- 24210051 TI - In vivo hepatocyte MR imaging using lactose functionalized magnetoliposomes. AB - The aim of this study was to assess a novel lactose functionalized magnetoliposomes (MLs) as an MR contrast agent to target hepatocytes as well as to evaluate the targeting ability of MLs for in vivo applications. In the present work, 17 nm sized iron oxide cores functionalized with anionic MLs bearing lactose moieties were used for targeting the asialoglycoprotein receptor (ASGP r), which is highly expressed in hepatocytes. Non-functionalized anionic MLs were tested as negative controls. The size distribution of lactose and anionic MLs was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After intravenous administration of both MLs, contrast enhancement in the liver was observed by magnetic resonance imaging (MRI). Label retention was monitored non-invasively by MRI and validated with Prussian blue staining and TEM for up to eight days post MLs administration. Although the MRI signal intensity did not show significant differences between functionalized and non functionalized particles, iron-specific Prussian blue staining and TEM analysis confirmed the uptake of lactose MLs mainly in hepatocytes. In contrast, non functionalized anionic MLs were mainly taken up by Kupffer and sinusoidal cells. Target specificity was further confirmed by high-resolution MR imaging of phantoms containing isolated hepatocytes, Kupffer cell (KCs) and hepatic stellate cells (HSCs) fractions. Hypointense signal was observed for hepatocytes isolated from animals which received lactose MLs but not from animals which received anionic MLs. These data demonstrate that galactose-functionalized MLs can be used as a hepatocyte targeting MR contrast agent to potentially aid in the diagnosis of hepatic diseases if the non-specific uptake by KCs is taken into account. PMID- 24210052 TI - Mitochondrial metabolism and stress response of yeast: Applications in fermentation technologies. AB - Mitochondria are sites of oxidative respiration. During sake brewing, sake yeasts are exposed to long periods of hypoxia; the structure, role, and metabolism of mitochondria of sake yeasts have not been studied in detail. It was first elucidated that the mitochondrial structure of sake yeast transforms from filamentous to dotted structure during sake brewing, which affects malate metabolism. Based on the information of yeast mitochondria during sake brewing, practical technologies have been developed; (i) breeding pyruvate-underproducing sake yeast by the isolation of a mutant resistant to an inhibitor of mitochondrial pyruvate transport; and (ii) modifying malate and succinate production by manipulating mitochondrial activity. During the bread-making process, baker's yeast cells are exposed to a variety of baking-associated stresses, such as freeze-thaw, air-drying, and high sucrose concentrations. These treatments induce oxidative stress generating reactive oxygen species due to mitochondrial damage. A novel metabolism of proline and arginine catalyzed by N acetyltransferase Mpr1 in the mitochondria eventually leads to synthesis of nitric oxide, which confers oxidative stress tolerance on yeast cells. The enhancement of proline and arginine metabolism could be promising for breeding novel baker's yeast strains that are tolerant to multiple baking-associated stresses. These new and practical methods provide approaches to improve the processes in the field of industrial fermentation technologies. PMID- 24210053 TI - Energy profiling of demersal fish: a case-study in wind farm artificial reefs. AB - The construction of wind farms introduces artificial hard substrates in sandy sediments. As Atlantic cod (Gadus morhua) and pouting (Trisopterus luscus) tend to aggregate in order to feed around these reefs, energy profiling and trophic markers were applied to study their feeding ecology in a wind farm in the Belgian part of the North Sea. The proximate composition (carbohydrates, proteins and lipids) differed significantly between liver and muscle tissue but not between fish species or between their potential prey species. Atlantic cod showed to consume more energy than pouting. The latter had a higher overall energy reserve and can theoretically survive twice as long on the available energy than cod. In autumn, both fish species could survive longer on their energy than in spring. Polyunsaturated fatty acids were found in high concentrations in fish liver. The prey species Jassa and Pisidia were both rich in EPA while Jassa had a higher DHA content than Pisidia. Energy profiling supported the statement that wind farm artificial reefs are suitable feeding ground for both fish species. Sufficient energy levels were recorded and there is no indication of competition. PMID- 24210054 TI - Shell formation in cultivated bivalves cannot be part of carbon trading systems: a study case with Mytilus galloprovincialis. AB - Respiration and calcium carbonate (CaCO3) production by the farmed Mediterranean mussel Mytilus galloprovincialis were calculated to assess their importance as carbon dioxide (CO2) sink/source in the Sacca di Scardovari (Po Delta River, Italy). The ratio of CO2 released to CaCO3 precipitated was calculated as a function of the near-bottom temperature. From our estimates, M. galloprovincialis sequestered 136.6 mol(CO2) m(-2) year(-1) for shell formation, but the CO2 fluxes due to respiration and calcification resulted 187.8 and 86.8 mol(CO2) m(-2) year( 1) respectively. Mussel farming seems therefore to be a significant additional source of CO2 to seawater. For this reason shell formation in cultivated shellfish cannot be part of carbon trading systems. PMID- 24210055 TI - Studies on lung cancer management in routine practice. PMID- 24210056 TI - PSI, CURB-65, SMART-COP or SCAP? And the winner is... SMART DOCTORS. PMID- 24210057 TI - Tailored surgery for drug-resistant epilepsy due to temporal pole encephalocele and microdysgenesis. PMID- 24210059 TI - Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. AB - PURPOSE: To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA). METHODS: Retrospective data were collected from an electronic database and medical records. Blood samples were obtained and drug concentrations analyzed as a part of routine therapeutic drug monitoring (TDM). Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism (rs776746) by allelic discrimination assay using real-time polymerase chain reaction technique (real time PCR) was performed. Pharmacokinetic parameters of CBZ; clearance and dose adjusted CBZ levels in patients with different genotypes were calculated and compared. RESULTS: Of the 70 patients assessed, 8 (11%) patients were homozygous CYP3A5*1/*1, 28 (40%) patients were heterozygous CYP3A5*1/*3, and 34 (49%) patients were homozygous CYP3A5*3/*3. The CBZ clearance and dose-adjusted CBZ levels did not significantly differ between patients with CYP3A5*1 and CYP3A5*3 alleles when CBZ was used as monotherapy. For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded. Nevertheless, it was observed that AEDs significantly increased CBZ clearance only in patients carrying the active CYP3A5*1 allele. CONCLUSIONS: When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers. The dosage regimen should be adjusted accordingly to gain a better clinical outcome.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210058 TI - Protecting child health and nutrition status with ready-to-use food in addition to food assistance in urban Chad: a cost-effectiveness analysis. AB - BACKGROUND: Despite growing interest in use of lipid nutrient supplements for preventing child malnutrition and morbidity, there is inconclusive evidence on the effectiveness, and no evidence on the cost-effectiveness of this strategy. METHODS: A cost effectiveness analysis was conducted comparing costs and outcomes of two arms of a cluster randomized controlled trial implemented in eastern Chad during the 2010 hunger gap by Action contre la Faim France and Ghent University. This trial assessed the effect on child malnutrition and morbidity of a 5-month general distribution of staple rations, or staple rations plus a ready-to-use supplementary food (RUSF). RUSF was distributed to households with a child aged 6 36 months who was not acutely malnourished (weight-for-height > = 80% of the NCHS reference median, and absence of bilateral pitting edema), to prevent acute malnutrition in these children. While the addition of RUSF to a staple ration did not result in significant reduction in wasting rates, cost-effectiveness was assessed using successful secondary outcomes of cases of diarrhea and anemia (hemoglobin <110 g/L) averted among children receiving RUSF.Total costs of the program and incremental costs of RUSF and related management and logistics were estimated using accounting records and key informant interviews, and include costs to institutions and communities. An activity-based costing methodology was applied and incremental costs were calculated per episode of diarrhea and case of anemia averted. RESULTS: Adding RUSF to a general food distribution increased total costs by 23%, resulting in an additional cost per child of 374 EUR, and an incremental cost per episode of diarrhea averted of 1,083 EUR and per case of anemia averted of 3,627 EUR. CONCLUSIONS: Adding RUSF to a staple ration was less cost-effective than other standard intervention options for averting diarrhea and anemia. This strategy holds potential to address a broad array of health and nutrition outcomes in emergency settings where infrastructure is weak and other intervention options are infeasible in the short-term. However, further research is needed to establish the contexts in which RUSF is most effective and cost effective in preventing acute malnutrition and morbidity among vulnerable children, compared to other options. PMID- 24210060 TI - Effectiveness of academic detailing to optimize medication prescribing behaviour of family physicians. AB - PURPOSE: To synthesize current knowledge about the effectiveness and the magnitude of the effect, of Academic Detailing (AD), as a stand-alone intervention, at modifying drug prescription behavior of Family Physicians (FPs) in primary care settings. METHODS: A search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases of all English language articles between January 1983 and July 2010 was conducted. We hand-searched the bibliographies of articles retrieved from the electronic search to identify additional studies. Inclusion criteria were: full-length articles describing original research; randomized controlled trial (RCT), or observational study design with a control group; studies of AD delivered to FPs; AD as a stand-alone intervention; drug prescription as the target behavior. Data extraction was done independently by two reviewers. Outcomes evaluated were: the difference in relative change in prescription rate between the intervention and control groups; the difference in absolute change in prescription rate between the intervention and control groups; and effect size, calculated as the standardized mean difference. RESULTS: 11 RCTs and 4 observational studies were included. Five RCTS described results showing effectiveness, while 2 RCTs reported a positive effect on some of the target drugs. Two observational studies found AD to be effective, while 2 did not. The median difference in relative change among the studies reviewed was 21% (interquartile range 43.75%) for RCTs, and 9% (interquartile range 8.5%) for observational studies. The median effect size among the studies reviewed was - 0.09 (interquartile range 2.73). CONCLUSION: This systematic review demonstrates that AD can be effective at optimizing prescription of medications by FPs. Although variable, the magnitude of the effect is moderate in the majority of studies. This systematic review also provides evidence supportive of the use of AD as a strategy to promote evidence based prescription of medications or incorporation of clinical guidelines into clinical practice. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210061 TI - Glycogen phosphorylase-a is a common target for anti-diabetic effect of iridoid and secoiridoid glycosides. AB - PURPOSE: Diabetes mellitus is characterized by hyperglycemia resulting from defects in insulin secretion, action or both. The use of medicinal plants for the treatment of diabetes mellitus dates back from the Ebers papyrus of about 1550 B.C. One of the major problems with herbal drugs is that the active ingredients are not well defined. It is important to know the active components and their molecular interactions which will help to analyze their therapeutic efficacy and also to standardize the product. There are a number of medicinal plants known for their anti-diabetic effect that possess similarities in their active chemical components, e.g. iridoid and secoiridoid glycosides. METHODS: In this study, we have compared the structure of various iridoid and secoiridoid glycosides to design a novel pharmacophore. We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. CONCLUSION: By using docking studies, we are proposing, for the first time, that inhibition of glycogen phosphorylase-a activity is a common target for iridoids and secoiridoids to elicit anti-diabetic effects. This article is open to POST PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210062 TI - Transferrin receptor mediated brain uptake during ischemia and reperfusion. AB - PURPOSE: Drug delivery by transferrin receptor-mediated transport at the blood brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse model of brain focal ischemia, permanent or transient middle cerebral artery occlusion (MCAO). METHODS: Brain accumulation of 125I-labeled 8D3, a mouse-specific transferrin receptor antibody, or of the isotype control UPC-10 used as vascular marker, was measured autoradiographically by phosphorimaging in the core ischemic region on cryostat brain sections up to 24h after ischemia or reperfusion. Cerebral blood flow was quantitatively determined in the same animals after administration of 99mTc-ECD (Neurolite). RESULTS: Apparent volume of distribution obtained with UPC 10 indicated no significant nonspecific leakage of the blood-brain barrier at any time point. Although brain uptake of 8D3 gradually declined compared to healthy tissue under MCAO, VD remained significantly higher than VD of UPC-10 up to 5h. In transient MCAO the brain uptake recovered to levels as in healthy tissue immediately after reperfusion. CONCLUSION: Transferrin receptor-mediated brain uptake, which is an energy dependent vesicular transport process, is sensitive to reduction in blood supply but remains partially functional for several hours after onset of ischemia. The uptake shows complete recovery after reperfusion. These results support the use of transferrin receptor-mediated brain drug delivery in the early phase of ischemia and in the phase when blood flow is restored. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210063 TI - Effect of terpenes on the skin permeation of lomerizine dihydrochloride. AB - PURPOSE: Lomerizine dihydrochloride (LOM) is a Ca2+ channel blocker used as an antimigraine drug, which is currently administered orally in Japan. We therefore investigated the effect of terpenes in propylene glycol (PG) solvent on the percutaneous absorption of LOM by hairless mouse skin. METHODS: Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), confocal laser scanning microscopy (CLSM), and small angle X-ray scattering (SAXS) were carried out to analyze the effects of terpene enhancers on the biophysical properties of the stratum corneum (SC) of the skin. RESULTS: Of the terpenes tested, the highest permeation rate of LOM (28.8 mg/cm2/h) was observed with 1,8-cineole, while nerolidol conferred the lowest enhancement of LOM flux (14.2 mg/cm2/h). ATR FTIR studies revealed that terpenes/PG induced higher CH2 stretching frequencies of SC lipids than PG alone. The extent of penetration of the lipophilic fluorescence probes Nile Red and DiI was measured by CLSM in in vitro skin permeation studies, using either PG or terpenes/PG as skin permeation enhancers. With PG alone, both fluorescence dyes were undetectable in the skin. In contrast, when co-administered with terpenes/PG, both probes were distributed into the intercellular space between corneocytes and detected in the deeper layers of the skin. SAXS measurements showed that in SC treated with a combination of 1,8 cineole and PG, the scattering peak of the SC was broad and very weak in intensity compared to untreated SC, whereas pretreatment with PG alone did not alter the peak profile. CONCLUSION: A combination of terpenes and PG enhance the skin permeation of LOM. Our findings suggest that the mechanism for this effect involves the ability of terpenes to increase the fluidity of SC lipids, thus enhancing the distribution of LOM into the intercellular region of the SC. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210064 TI - Innovations in epilepsy management - an overview. AB - In the past twenty years, thirteen new antiepileptic drugs (AEDs) have been introduced, each differing in their efficacy spectrum, mechanism of action, pharmacokinetics, safety and tolerability profiles. These newer AEDs symbolize a welcoming future in the management of epilepsy because they are able to produce a remarkable reduction in seizure frequency in up to 40% to 50% of the patients who had been refractory to old generation drugs. Despite the current availability of these new drugs, only a few patients with truly refractory seizures can be made seizure free. Although the newer agents are not superior to that of the older drugs, some have been shown to be non-inferior in terms of their efficacy. They offer additional advantages like better tolerability, ease of use, reduced interaction profile. Even though in most situations the older generation drugs still represent the best choice, advancing studies show that in many conditions, new generation drugs may be entirely vindicated for initial therapy. This urges a need for the search of novel and more efficacious new antiepileptic drugs in the management of uncontrollable seizures. More direct comparisons of newer versus newer and newer versus older drugs in clinical trials, both for monotherapy and adjunctive therapy must be conducted. More than 20 compounds with promising antiepileptic and neuroprotective properties have been discovered and are under various stages of drug development. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210065 TI - Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties. AB - PURPOSE: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. METHODS: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. RESULTS: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC. CONCLUSIONS: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210066 TI - Statins against drug-induced nephrotoxicity. AB - Drug-induced nephrotoxicity (DIN) accounts for up to 60% of hospital acquired acute kidney injury with considerable morbidity and mortality. Several efforts have been made to reduce drug-induced nephrotoxicity; however, DIN remains a matter of concern. Statins with their antioxidant, anti-inflammatory and anti apoptotic effects may have the potential to protect kidney against DIN. The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs. Materials for this review were obtained by searching Medline, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. Key words used as search terms included "statin", "3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors, "HMG-CoA reductase inhibitors", "nephroprotective", "renoprotective", "drug-induced renal diseases", "drug induced nephrotoxicity", "drug-induced renal toxicity", "drug-induced nephropathy", "drug-induced renal side effects", and "contrast-induced nephropathy". This search was performed without time limitation. Only English language articles were included in this review. This review concluded that chronic statin user may be less prone to contrast-induced nephropathy (CIN) compared with statin non-users. Short-term high dose statin administration may also reduce the incidence of CIN in statin naive patients. This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction, but probably not in patients with moderate to severe renal dysfunction. Based on available animal data, statins may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, however, theses animal results have not yet been confirmed by human data. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210067 TI - Enhanced prokaryotic expression of dengue virus envelope protein. AB - PURPOSE: To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. METHODS: A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize mice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. RESULTS: The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. CONCLUSION: The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts. This article is open to POST PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210068 TI - Partial least square and hierarchical clustering in ADMET modeling: prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands. AB - PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 alpha adrenergic and imidazoline-receptors ligands were examined in Quantitative Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (MUeff at pH 4.4, MUeff at pH 7.4, and MUeff at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related alpha-adrenergic/imidazoline receptor ligands.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 alpha-adrenergic and imidazoline receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (MUeff at pH 4.4, MUeff at pH 7.4, and MUeff at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related alpha-adrenergic/imidazoline receptor ligands. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 24210069 TI - Pharmacokinetics of a cytochrome P450 2E1 probe, chlorzoxazone, and its 6-hydroxy metabolite in poloxamer 407-induced hyperlipidemic rats. AB - PURPOSE: To evaluate the possible changes in CYP2E1 expression and activity in hyperlipidemia (HL), we evaluated the pharmacokinetics of chlorzoxazone (CZX) as a CYP2E1 probe in rats with HL induced by poloxamer 407 (HL rats). METHODS: The pharmacokinetics of CZX and its 6-hydroxy metabolite (OH-CZX) were evaluated after intravenous administration of 20 mg/kg CZX to both control and HL rats. We also examined changes in the expression of CYP2E1 and its in vitro metabolic activity in hepatic microsomal fractions from HL rats. RESULTS: The total area under the plasma concentration-time curve (AUC) of CZX in the HL rats after its intravenous administration was comparable with that in the controls due to unchanged non-renal clearance (CLNR). The AUC of OH-CZX and AUCOH-CZX/AUCCZX ratios in HL rats also remained unchanged. This was primarily due to the comparable hepatic CLint for metabolism of CZX to OH-CZX via CYP2E1 between the control and HL rats as a result of unchanged expression of CYP2E1 in HL rats. CONCLUSIONS: This is the first study to evaluate CYP2E1 expression and activity in HL rats and their effects on the pharmacokinetics of a CYP2E1 probe drug. These findings have potential therapeutic implications assuming that the HL rat model qualitatively reflects similar changes in patients with HL. PMID- 24210070 TI - A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. AB - BACKGROUND: Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors (AIs) and often results in premature drug discontinuation. METHODS: We conducted a randomised controlled trial of electro-acupuncture (EA) as compared to waitlist control (WLC) and sham acupuncture (SA) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs. Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit. Acupuncturists administered SA using Streitberger (non-penetrating) needles at non-traditional acupuncture points without electro-stimulation. The primary end-point was pain severity by Brief Pain Inventory (BPI) between EA and WLC at Week 8; durability of response at Week 12 and comparison of EA to SA were secondary aims. FINDINGS: Of the 67 randomly assigned patients, mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 (-2.2 versus -0.2, p=0.0004) and at Week 12 (-2.4 versus -0.2, p<0.0001). Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 (-2.0 versus 0.2, p=0.0006) and Week 12 (-2.1 versus -0.1, p=0.0034). SA produced a magnitude of change in pain severity and pain-related interference at Week 8 (-2.3, -1.5 respectively) and Week 12 (-1.7, -1.3 respectively) similar to that of EA. Participants in both EA and SA groups reported few minor adverse events. INTERPRETATIONS: Compared to usual care, EA produced clinically important and durable improvement in arthralgia related to AIs in breast cancer patients, and SA had a similar effect. Both EA and SA were safe. PMID- 24210071 TI - Morphine improved the antitumor effects on MCF-7 cells in combination with 5 Fluorouracil. AB - BACKGROUND: The most frequently used opioid in cancer pain management is morphine which remains a cornerstone for the management of cancer pain, due to the largest experience existing among physicians and widely availability in a variety of formulation. Considering that analgesics on cancer pain is often under the condition of chemotherapy and 5-Fluorouracil (5-FU) is widely used today as a potent drug for the treatment of advanced cancers, whether analgesics such as morphine, interferes the chemotherapy such as 5-FU, arose as a considerable problem. METHODS: In this study, the MCF-7 breast cancer cells were used to determine the antitumor effects of the 5-FU in combination with morphine. The cell proliferation was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay and the apoptosis was determined by the Annexin V/PI staining and flow cytometry. The immunocytochemistry and western blot was used to determine the Bcl-2 and Bax expression. RESULTS: It was shown that in MCF-7 cells, the proliferation was inhibited, the apoptosis was promoted, the Bcl-2 expression was suppressed and the Bax expression was promoted by both 5 FU alone and morphine alone, while the superior effects were achieved in combination with the two drugs. CONCLUSION: These results suggest that the morphine may have the beneficial effects on the antitumor chemotherapy with 5-FU, in stead of interferential effects. PMID- 24210072 TI - MicroRNA-29a upregulates MMP2 in oral squamous cell carcinoma to promote cancer invasion and anti-apoptosis. AB - Abnormal microRNA expression is a common and important feature of human malignancies. Matrix metalloproteinase 2 (MMP2), which has been reported in several cancers, plays important roles in cancer progression. However, the microRNA regulatory mechanism on MMP2 expression remains unclear. In this study, we first detected MMP2 and microRNA-29a (miR-29a) expression in oral squamous carcinoma (OSCC) specimens, which showed that MMP2 was higher in OSCC cancer tissues than adjacent tissues but that miR-29a was lower in OSCC cancer tissues than adjacent tissues. Then, we confirmed that miR-29a, which directly targeted 3'-UTR of MMP2 gene, negatively regulated MMP2 expression by miR-29a transfection and luciferase reporter assay. Exogenous overexpression of miR-29a inhibited OSCC cell invasion and anti-apoptosis significantly in vitro. Whereas, knockdown of miR-29a promoted OSCC cell invasion and induced drug-resistance in vitro. This study suggests that miR-29a plays an inhibiting role in the progression of OSCC, which may be a potentially therapeutic approach in the future. PMID- 24210073 TI - Sphingosine-1-phosphate in chronic intestinal inflammation and cancer. AB - Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, and the kinase that produces it have now emerged as key regulators of numerous cellular processes involved in inflammation and cancer. Here, we review the importance of S1P in colitis and colitis-associated cancer (CAC) and discuss our recent work demonstrating that S1P produced by upregulation of SphK1 during colitis and associated cancer is essential for production of the multifunctional NF-kappaB regulated cytokine IL-6, persistent activation of the transcription factor Stat3, and consequent upregulation of the S1P receptor, S1PR1. The effectiveness of the pro-drug FTY720 (known as fingolimod), approved for the treatment of multiple sclerosis, has become the gold standard for S1P-centric drugs, and will be used to illustrate the therapeutic value of modulating SphK1 and S1P receptor functions. We will discuss our recent results showing that FTY720/fingolimod administration interferes with the SphK1/S1P/S1PR1 axis and suppresses the NF kappaB/IL-6/Stat3 malicious amplification loop and CAC. These preclinical studies suggest that FTY720/fingolimod may be useful in treating colon cancer in individuals with ulcerative colitis. PMID- 24210074 TI - Thalamic cramplike pain. AB - IMPORTANCE: We describe a case of cramplike pain after a left thalamic ischemic stroke, a neglected type of central post-stroke pain and we describe its neuroanatomical correlates. OBSERVATIONS: A 68-year-old right-handed man presented with right arm, leg, and flank cramplike pain noted upon awakening. Neurological examination was normal, with no evidence of objective sensory abnormalities. Because of the nature of the pain and the preserved sensory function, we first did not consider stroke as a potential cause, and suspected that pain was related to the combined effect of intense physical exercising on the right side and the use of statins. Diffusion-weighted magnetic resonance imaging showed an acute ischemic infarction within the left thalamus. By registering high-resolution 3 T T1-weighted and T2-weighted magnetic resonance images to the Talairach atlas, we showed the infarction is within the border between the pulvinar and the ventral posterior medial nuclei. Brodmann's areas 3, 1, 2, 4 and 6 were identified as the cortical correlates of the ischemic lesion by diffusion tensor tractography. CONCLUSIONS AND RELEVANCE: Thalamic cramplike pain should be recognized as a type of central post-stroke pain, probably produced by lesions localized to the border between the ventral posterior and pulvinar nuclei and connected to the ipsilateral primary somatosensory cortex and primary and secondary motor cortices. PMID- 24210075 TI - Hemispheric lateralization of microstructural white matter abnormalities in children with active benign childhood epilepsy with centrotemporal spikes (BECTS): a preliminary DTI study. AB - PURPOSE: The deficit of white matter is reported to be involved during the disease progression in patients with benign childhood epilepsy with centrotemporal spikes (BECTS). The aim of this study is to investigate patterns of white matter damage in children with BECTS with left- or right-hemispheric focus by using diffusion tensor imaging (DTI), and its relationship with the cofactors such duration, seizure frequency and handedness. METHODS: Diffusion tensor imaging (DTI) was performed in twenty-eight children with BECTS and eighteen healthy controls. The data were analyzed using both tract-based spatial statistics (TBSS) and region of interest (ROI) analyses. Correlations were investigated between the fractional anisotropy (FA) values of the identified altered regions and clinical features such as age, age of onset and seizure frequency. RESULTS: The TBSS analysis revealed that white matter impairment in children with rolandic spikes on the ipsilateral hemisphere was much wider. The FA value was significantly lower in the body of the corpus callosum and forceps minor in BECTS patients with spikes on the ipsilateral hemisphere. The seizure frequency correlated positively with the FA values of body of corpus callosum (CC), bilateral cingulate gyrus and left uncinate fasciculi (UA). CONCLUSION: The impaired WM integrity in patients with BECTS was greater in patients with spikes on the dominant hemisphere, possibly due to the greater vulnerability of the left hemisphere and excitotoxic effects of seizures. PMID- 24210076 TI - Anti-NMDA receptor encephalitis presenting with total insomnia--a case report. AB - Fatal insomnia (FI) is the first diagnosis to be considered by most neurologists when approaching a patient presenting with total insomnia followed by personality and cognitive changes, disturbance of alertness, autonomic hyperactivation and movement abnormalities. We report the case of a 30 year-old male patient who presented with total insomnia followed by episodes of psychomotor restlessness resembling anxiety attacks. Twenty days later, he developed refractory convulsive status epilepticus with admission to Intensive Care Unit. He progressed to a state of reduced alertness and responsiveness, presenting periods of agitation with abnormal dyskinetic movements, periods of autonomic instability and central hypoventilation. Workup revealed antibodies against N-methyl-d-aspartate receptor (NMDAR). Immunotherapy treatment led to a very significant improvement with the patient presenting only slight frontal lobe dysfunction after one year of recovery. To the best of our knowledge this is the first report of a patient with anti-NMDAR encephalitis first presenting with total insomnia. Our aim is to alert that anti-NMDAR encephalitis must be considered in the differential diagnosis of FI, especially in sporadic cases. Distinguishing the two conditions is very important as, contrarily to the fatal disclosure of FI, anti-NMDAR encephalitis is potentially reversible with adequate treatment even after severe and prolonged disease. PMID- 24210077 TI - Detection of serious complications by MR imaging in asymptomatic young adults with repaired coarctation of the aorta. AB - BACKGROUND: Despite early repair, patients with aortic coarctation (CoA) continue to have a reduced life expectancy due to the development of late complications. We sought to define the rate of aortic abnormalities in patients with previous CoA repair, referred for surveillance magnetic resonance (MR) imaging. METHODS: We evaluated 59 asymptomatic adults consecutively for repaired CoA with MR imaging between 2008 and 2012. RESULTS: Patients were aged 29 +/- 8 (16-49) years; 34 males (58%) and 34 with bicuspid aortic valve (58%). Median age at the time of initial repair was two years. Surveillance MR imaging was performed 23 +/ 8 years post-procedure. The three most common interventions performed were subclavian-flap repair (25%), end-to-end repair (33%) and patch aortoplasty (33%). Re-intervention with balloon angioplasty or repeat surgery had been performed in 22% of subjects. There were 28 cases of recoarctation (48%), of which seven were at least moderate in severity. Repair site and ascending aortic aneurysm occurred in eight (14%) and four (7%) subjects, respectively. Freedom from any degree of recoarctation and other aortic complications was observed in eight subjects (14%). CONCLUSION: MR imaging detected a high rate of aortic abnormalities in asymptomatic adults after CoA repair, including 27% with clinically significant recoarctation and/or local aneurysm formation. PMID- 24210078 TI - Preoperative chemoradiation therapy with capecitabine/oxaliplatin and cetuximab in rectal cancer: long-term results of a prospective phase 1/2 study. AB - PURPOSE: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. METHODS AND MATERIALS: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. RESULTS: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). CONCLUSIONS: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not translate to poor survival in our clinical trial. PMID- 24210079 TI - Temporal nodal regression and regional control after primary radiation therapy for N2-N3 head-and-neck cancer stratified by HPV status. AB - PURPOSE: To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(-)] head-and-neck cancer (HNC). METHODS AND MATERIALS: All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV( ). Initial radiologic complete nodal response (CR) (<=1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV( ) HNC. Multivariate analysis identified outcome predictors. RESULTS: A total of 257 HPV(+) and 236 HPV(-) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(-) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(-) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(-) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(-) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(-) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(-) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01). CONCLUSIONS: HPV(+) LNs involute more quickly than HPV(-) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12 weeks after treatment. Post radiation neck dissection is advisable for all non-CR HPV(-)/non-CR N3 HPV(+) cases, but it may be avoided for selected non-CR N2 HPV(+) cases with a significant LN involution if they can undergo continued imaging surveillance. The role of positron emission tomography for response assessment should be investigated. PMID- 24210080 TI - Radioprotection and cell cycle arrest of intestinal epithelial cells by darinaparsin, a tumor radiosensitizer. AB - PURPOSE: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. METHODS AND MATERIALS: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. RESULTS: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. CONCLUSIONS: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy. PMID- 24210081 TI - An assessment of the current US radiation oncology workforce: methodology and global results of the American Society for Radiation Oncology 2012 Workforce Study. AB - PURPOSE: To determine the characteristics, needs, and concerns of the current radiation oncology workforce, evaluate best practices and opportunities for improving quality and safety, and assess what we can predict about the future workforce. METHODS AND MATERIALS: An online survey was distributed to 35,204 respondents from all segments of the radiation oncology workforce, including radiation oncologists, residents, medical dosimetrists, radiation therapists, medical physicists, nurse practitioners, nurses, physician assistants, and practice managers/administrators. The survey was disseminated by the American Society for Radiation Oncology (ASTRO) together with specialty societies representing other workforce segments. An overview of the methods and global results is presented in this paper. RESULTS: A total of 6765 completed surveys were received, a response rate of 19%, and the final analysis included 5257 respondents. Three-quarters of the radiation oncologists, residents, and physicists who responded were male, in contrast to the other segments in which two-thirds or more were female. The majority of respondents (58%) indicated they were hospital-based, whereas 40% practiced in a free-standing/satellite clinic and 2% in another setting. Among the practices represented in the survey, 21.5% were academic, 25.2% were hospital, and 53.3% were private. A perceived oversupply of professionals relative to demand was reported by the physicist, dosimetrist, and radiation therapist segments. An undersupply was perceived by physician's assistants, nurse practitioners, and nurses. The supply of radiation oncologists and residents was considered balanced. CONCLUSIONS: This survey was unique as it attempted to comprehensively assess the radiation oncology workforce by directly surveying each segment. The results suggest there is potential to improve the diversity of the workforce and optimize the supply of the workforce segments. The survey also provides a benchmark for future studies, as many changes in the healthcare field exert pressure on the workforce. PMID- 24210082 TI - The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. AB - PURPOSE: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. METHODS AND MATERIALS: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. RESULTS: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade >=3 pneumonitis were low and not significantly affected by tumor or target size. CONCLUSIONS: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm in tumor diameter or 100 cm(3) in tumor volume) but are associated with more nonlocal failures as well as poorer survival. These observations suggest these patients may benefit from more extensive staging or consideration of adjuvant therapy. PMID- 24210083 TI - Segmental ureterectomy for upper tract urothelial carcinoma: two procedures with different indications. PMID- 24210084 TI - Commentary on "Androgen-deprivation therapy alone or with docetaxel in non castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial." Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Theodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M, Medical Oncology and Biostatistics, Institut Paoli-Calmettes, Marseille, France. Lancet Oncol 2013;14(2):149-58 [Epub 2013 Jan 8]. AB - BACKGROUND: Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (i.e., hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer. METHODS: In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m(2) intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00104715. FINDINGS: Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39-63). Median overall survival was 58 9 months (95% CI 50 8-69 1) in the group given ADT plus docetaxel and 54 2 months (42 2-not reached) in that given ADT alone (hazard ratio 1 01, 95% CI 0 75-1 36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group. INTERPRETATION: Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer. PMID- 24210085 TI - Commentary on "Abiraterone in metastatic prostate cancer without previous chemotherapy." Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators, Genitourinary Medical Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA. N Engl J Med 2013;368(2):138-48 [Epub 2012 Dec 10]; N Engl J Med 2013;368(6):584. AB - BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS: The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. CONCLUSIONS: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. PMID- 24210086 TI - Commentary on "Intermittent versus continuous androgen deprivation in prostate cancer." Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr., University of Michigan, Division of Hematology/Oncology, 1500 E Medical Center Dr., 7314 CC, Ann Arbor, MI. N Engl J Med 2013;368(14):1314-25. AB - BACKGROUND: Castration resistance occurs in most patients with metastatic hormone sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. METHODS: Men with newly diagnosed, metastatic, hormone sensitive prostate cancer, a performance status of 0 to 2, and a prostate specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. RESULTS: A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P = 0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. CONCLUSIONS: Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. PMID- 24210087 TI - Commentary on "Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial." Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, SchoffskiSchoffski P, Scheffold C, Weitzman AL, Hussain M, University of Michigan, Ann Arbor, MI. J Clin Oncol 2013;31(4):412-9. doi: 10.1200/JCO.2012.45.0494. Epub 2012 Nov 19. AB - PURPOSE: Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. PATIENTS AND METHODS: Patients received 100mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment. RESULTS: One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P<.001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by >= 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). CONCLUSION: Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. PMID- 24210088 TI - 'Are we there yet?' - operationalizing the concept of Integrated Public Health Policies. AB - OBJECTIVES: Although 'integrated' public health policies are assumed to be the ideal way to optimize public health, it remains hard to determine how far removed we are from this ideal, since clear operational criteria and defining characteristics are lacking. METHODS: A literature review identified gaps in previous operationalizations of integrated public health policies. We searched for an approach that could fill these gaps. RESULTS: We propose the following defining characteristics of an integrated policy: (1) the combination of policies includes an appropriate mix of interventions that optimizes the functioning of the behavioral system, thus ensuring that motivation, capability and opportunity interact in such a way that they promote the preferred (health-promoting) behavior of the target population, and (2) the policies are implemented by the relevant policy sectors from different policy domains. CONCLUSION: Our criteria should offer added value since they describe pathways in the process towards formulating integrated policy. The aim of introducing our operationalization is to assist policy makers and researchers in identifying truly integrated cases. The Behavior Change Wheel proved to be a useful framework to develop operational criteria to assess the current state of integrated public health policies in practice. PMID- 24210089 TI - West Nile virus, Texas, USA, 2012. AB - During the 2012 West Nile virus outbreak in Texas, USA, 1,868 cases were reported. Male patients, persons >65 years of age, and minorities were at highest risk for neuroinvasive disease. Fifty-three percent of counties reported a case; 48% of case-patients resided in 4 counties around Dallas/Fort Worth. The economic cost was >$47.6 million. PMID- 24210090 TI - Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. AB - BACKGROUND: Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity. OBJECTIVE: To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naive to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr. INTERVENTION: Men were randomized to receive a GnRH agonist or an antagonist for either 3-7 mo (n=642) or 12 mo (n=1686). Treatment groups were balanced for common baseline characteristics. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death. RESULTS AND LIMITATIONS: Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26-0.74; p=0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating. CONCLUSIONS: GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists. PMID- 24210091 TI - Patient-reported outcomes in randomised controlled trials of prostate cancer: methodological quality and impact on clinical decision making. AB - CONTEXT: Patient-reported outcomes (PRO) data from randomised controlled trials (RCTs) are increasingly used to inform patient-centred care as well as clinical and health policy decisions. OBJECTIVE: The main objective of this study was to investigate the methodological quality of PRO assessment in RCTs of prostate cancer (PCa) and to estimate the likely impact of these studies on clinical decision making. EVIDENCE ACQUISITION: A systematic literature search of studies was undertaken on main electronic databases to retrieve articles published between January 2004 and March 2012. RCTs were evaluated on a predetermined extraction form, including (1) basic trial demographics and clinical and PRO characteristics; (2) level of PRO reporting based on the recently published recommendations by the International Society for Quality of Life Research; and (3) bias, assessed using the Cochrane Risk of Bias tool. Studies were systematically analysed to evaluate their relevance for supporting clinical decision making. EVIDENCE SYNTHESIS: Sixty-five RCTs enrolling a total of 22 071 patients were evaluated, with 31 (48%) in patients with nonmetastatic disease. When a PRO difference between treatments was found, it related in most cases to symptoms only (n=29, 58%). Although the extent of missing data was generally documented (72% of RCTs), few reported details on statistical handling of this data (18%) and reasons for dropout (35%). Improvements in key methodological aspects over time were found. Thirteen (20%) RCTs were judged as likely to be robust in informing clinical decision making. Higher-quality PRO studies were generally associated with those RCTs that had higher internal validity. CONCLUSIONS: Including PRO in RCTs of PCa patients is critical for better evaluating the treatment effectiveness of new therapeutic approaches. Marked improvements in PRO quality reporting over time were found, and it is estimated that at least one-fifth of PRO RCTs have provided sufficient details to allow health policy makers and physicians to make critical appraisals of results. PATIENT SUMMARY: In this report, we have investigated the methodological quality of PCa trials that have included a PRO assessment. We conclude that including PRO is critical to better evaluating the treatment effectiveness of new therapeutic approaches from the patient's perspective. Also, at least one-fifth of PRO RCTs in PCa have provided sufficient details to allow health policy makers and physicians to make a critical appraisal of results. PMID- 24210092 TI - Flavanone glycosides from Bidens gardneri Bak. (Asteraceae). AB - LC-DAD-MS/MS analysis of the Brazilian medicinal plant Bidens gardneri Bak. (Asteraceae) results in identification of eleven phenolic compounds. HRESIMS, MS/MS and UV data analyses, with phytochemicals isolation guided by MS data, results in flavanones-(-)-4'-methoxy-7-O-beta-D-glucopyranosyl-8,3' dihydroxyflavanone; (-)-7-O-(6"-E-p-coumaroyl)-beta-D-glucopyranosyl-8,3',4' trihydroxyflavanone; and (-)-4'-methoxy-7-O-(6"-acetyl)-beta-D-glucopyranosyl 8,3'-dihydroxyflavanone being identified-together with four known compounds. The absolute configurations of two of the flavanones were determined as 2S via circular dichroism. PMID- 24210093 TI - Evidence of massive global synchronization and the consciousness: comment on "Consciousness in the universe: a review of the 'Orch OR' theory" by Hameroff and Penrose. PMID- 24210094 TI - The multifaceted effect of PB1-F2 specific antibodies on influenza A virus infection. AB - PB1-F2 is a small influenza A virus (IAV) protein encoded by an alternative reading frame of the PB1 gene. During IAV infection, antibodies to PB1-F2 proteins are induced. To determine their function and contribution to virus infection, three distinct approaches were employed: passive transfer of anti-PB1 F2 MAbs and polyclonal antibodies, active immunization with PB1-F2 peptides and DNA vaccination with plasmids expressing various parts of PB1-F2. Mostly N terminal specific antibodies were detected in polyclonal sera raised to complete PB1-F2. Passive and active immunization revealed that antibodies recognizing the N-terminal part of the PB1-F2 molecule have no remarkable effect on the course of IAV infection. Interestingly antibodies against the C-terminal region of PB1-F2, obtained by immunization with KLH-PB1-F2 C-terminal peptide or DNA immunization with pC-ter.PB1-F2 plasmid, partially protected mice against virus infection. To our knowledge, this is the first report demonstrating the biological relevance of humoral immunity against PB1-F2 protein in vivo. PMID- 24210095 TI - Treg depletion attenuates the severity of skin disease from ganglionic spread after HSV-2 flank infection. AB - Regulatory T cells (Tregs) attenuate lesion severity and disease after HSV ocular or genital infection, but their role in cutaneous infection remains unclear. Treg depletion (anti-CD25 mAb in C57BL/6 mice or diphtheria toxin (DT) in DEREG mice) prior to tk-deficient HSV-2 flank infection significantly decreased skin lesion severity, granulocyte receptor-1(Gr-1(+)) cell number, and chemokine (KC) expression in the secondary skin, but significantly increased immune effectors and chemokine expression (MCP-1, KC, VEGF-A) in the draining LN, and activated, interferon-gamma producing CD8(+)T cells in the ganglia. Treg depletion also significantly reduced HSV-2 DNA in the ganglia. Thus, Tregs increase the severity of recurrent skin lesions, and differentially alter chemokine expression and immune effector homing in the skin and LN after cutaneous infection, and limit CD8(+) T cell responses in the ganglia. Our data suggests that effects of Treg manipulation on recurrent herpes lesions should be considered when developing Treg mediated therapeutics. PMID- 24210096 TI - Tombusvirus replication depends on Sec39p endoplasmic reticulum-associated transport protein. AB - Positive-stranded RNA viruses subvert subcellular membranes to built viral replicases complexes (VRCs) in infected cells. Tombusviruses use peroxisomal membranes for the assembly of their VRCs and they can efficiently switch to the endoplasmic reticulum membrane in the absence of peroxisomes. In this paper, we show that the ER-resident Sec39p vesicular transport protein is critical for the formation of active VRCs in yeast model host. Repression of Sec39p expression in yeast or in plants resulted in greatly reduced tombusvirus accumulation. Moreover, the purified tombusvirus replicase from Sec39p-depleted yeast cells showed low in vitro activity. Also, tombusvirus RNA replication was poor in cell free extracts or in isolated ER membranes from yeast with repressed Sec39p expression. The tombusvirus p33 replication protein was mislocalized to the ER when Sec39p was depleted in yeast. Overall, Sec39p is the first peroxisomal biogenesis protein characterized that is critical for tombusvirus replication in yeast and plants. PMID- 24210097 TI - Evolutionarily conserved residues at an oligomerization interface of the influenza A virus neuraminidase are essential for viral survival. AB - Neuraminidase (NA) is a homotetramer viral surface glycoprotein that is essential for virus release during influenza virus infections. Previous studies have not explored why influenza NA forms a tetramer when the bacterial monomer NA already exhibits excellent NA enzymatic activity levels. In this study, we focused on 28 highly conserved residues among all NA subtypes, identifying 21 of 28 positions as crucial residues for viral survival by using reverse genetics. Maintaining NA enzymatic activity levels is critical and numerous conserved residues were located at the oligomerization interface; however, these mutations did not affect NA enzymatic activity levels or NA cellular localization, but rather affected the stability of NA oligomerization, suggesting that the oligomerization of NA is essential for viral viability. An increased understanding of the biological functions of NA, in particular NA oligomerization, could facilitate an alternative design for antivirals to combat influenza virus infections. PMID- 24210099 TI - Hsp70 positively regulates porcine circovirus type 2 replication in vitro. AB - The Hsp70 chaperone plays a central role in multiple processes within cells. Porcine circovirus type 2 (PCV2) is the essential causal agent of post-weaning multisystemic wasting syndrome (PMWS), which has spread worldwide. But the mechanism of PCV2 replication remains poorly understood. In this study, we firstly found the positive effect of heat stress on the replication of PCV2 in the continuous porcine monocytic cell line 3D4/31. Downregulation of Hsp70 by the specific chaperone inhibitor Quercetin or RNA interference and upregulation of Hsp70 by expression from a recombinant adenovirus showed that Hsp70 enhanced PCV2 genome replication and virion production. A specific interaction between Hsp70 and PCV2 Cap was confirmed by colocalization by confocal microscopy and co immunoprecipitation. Furthermore, the NF-kappaB pathway was activated and caspase 3 activity was reduced when Hsp70 was overexpressed in PCV2-infected 3D4/31 cells. These data suggested that Hsp70 positively regulated PCV2 replication, which being helpful for understanding the molecular mechanism of PCV2 infection. PMID- 24210098 TI - Metadata-driven comparative analysis tool for sequences (meta-CATS): an automated process for identifying significant sequence variations that correlate with virus attributes. AB - The Virus Pathogen Resource (ViPR; www.viprbrc.org) and Influenza Research Database (IRD; www.fludb.org) have developed a metadata-driven Comparative Analysis Tool for Sequences (meta-CATS), which performs statistical comparative analyses of nucleotide and amino acid sequence data to identify correlations between sequence variations and virus attributes (metadata). Meta-CATS guides users through: selecting a set of nucleotide or protein sequences; dividing them into multiple groups based on any associated metadata attribute (e.g. isolation location, host species); performing a statistical test at each aligned position; and identifying all residues that significantly differ between the groups. As proofs of concept, we have used meta-CATS to identify sequence biomarkers associated with dengue viruses isolated from different hemispheres, and to identify variations in the NS1 protein that are unique to each of the 4 dengue serotypes. Meta-CATS is made freely available to virology researchers to identify genotype-phenotype correlations for development of improved vaccines, diagnostics, and therapeutics. PMID- 24210100 TI - TGF-beta regulation of gene expression at early and late stages of HPV16-mediated transformation of human keratinocytes. AB - In our in vitro model for HPV16-mediated transformation, HPV16-immortalized human keratinocytes (HKc/HPV16) give rise to differentiation resistant, premalignant cells (HKc/DR). HKc/DR, but not HKc/HPV16, are resistant to growth inhibition by transforming growth factor beta (TGF-beta), due to a partial loss of TGF-beta receptor type I. We show that TGF-beta activates a Smad-responsive reporter construct in HKc/DR to about 50% of the maximum levels of activation observed in HKc/HPV16. To investigate the functional significance of residual TGF-beta signaling in HKc/DR, we compared gene expression profiles elicited by TGF-beta treatment of HKc/HPV16 and HKc/DR on Agilent 44k human whole genome microarrays. TGF-beta altered the expression of cell cycle and MAP kinase pathway genes in HKc/HPV16, but not in HKc/DR. However, epithelial-mesenchymal transition (EMT) responses to TGF-beta were comparable in HKc/HPV16 and HKc/DR, indicating that the signaling pathways through which TGF-beta elicits growth inhibition diverge from those that induce EMT in HPV16-transformed cells. PMID- 24210101 TI - Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: implications for ovarian cancer therapy. AB - In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46 positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNgamma and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. PMID- 24210102 TI - Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus. AB - Understanding the host response to influenza A virus infection is essential for developing intervention approaches. We show that infection of human alveolar epithelial cells and human bronchial epithelial cells with influenza A for 3h resulted in down-regulation of host hsa-miRNA-548an (miRNA-548an) which triggered the overexpression of influenza non-structural-1A binding protein (IVNS1ABP, herein referred to as NS1ABP). Reduced NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an mimic or increased NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an inhibitor provided evidence that miRNA-548an is involved in the regulation of NS1ABP. Transfection of cells with inhibitor led to reduced apoptosis of infected cells while transfection of mimic led to increased apoptosis and reduced influenza copy number suggesting that NS1ABP has a role in viral maintenance. Thus, miRNA-548an may be an important target in controlling the early stage infection of influenza A. PMID- 24210103 TI - Second site reversion of a mutation near the amino terminus of the HIV-1 capsid protein. AB - During HIV-1 morphogenesis, the precursor Gag protein is processed to release capsid (CA) proteins that form the mature virus core. In this process, the CA proteins assemble a lattice in which N-terminal domain (NTD) helices 1-3 are critical for multimer formation. Mature core assembly requires refolding of the N terminus of CA into a beta-hairpin, but the precise contribution of the hairpin core morphogenesis is unclear. We found that mutations at isoleucine 15 (I15), between the beta-hairpin and NTD helix 1 are incompatible with proper mature core assembly. However, a compensatory mutation of histidine 12 in the beta-hairpin to a tyrosine was selected by long term passage of an I15 mutant virus in T cells. The tyrosine does not interact directly with residue 15, but with NTD helix 3, supporting a model in which beta-hairpin folding serves to align helix 3 for mature NTD multimerization. PMID- 24210104 TI - Post translational modifications in adenovirus type 2. AB - We have combined 2-D SDS-PAGE with liquid chromatography-high resolving mass spectrometry (LC-MS) to explore the proteome of the adenovirus type 2 (Ad2) at the level of post translational modifications (PTMs). The experimental design included in-solution digestion, followed by titanium dioxide enrichment, as well as in-gel digestion of polypeptides after separation of Ad2 capsid proteins by 1 D and 2-D SDS-PAGE. All samples were analyzed using LC-MS with subsequent manual verification of PTM positions. The results revealed new phosphorylation sites that can explain the observed trains of protein spots observed for the pIII, pIIIa and pIV proteins. The pIIIa protein was found to be the most highly modified protein with now 18 verified sites of phosphorylation, three sites of nitrated tyrosine and one sulfated tyrosine. Nitrated tyrosines were also identified in pII. Lysine acetylations were detected in pII and pVI. The findings make the Ad2 virion much more complex than hitherto believed. PMID- 24210105 TI - Role of CD25(+) CD4(+) T cells in acute and persistent coronavirus infection of the central nervous system. AB - The influence of CD25(+)CD4(+) regulatory T cells (Treg) on acute and chronic viral infection of the central nervous system (CNS) was examined using a glial tropic murine coronavirus. Treg in the CNS were highest during initial T cell mediated virus control, decreased and then remained relatively stable during persistence. Anti-CD25 treatment did not affect CNS recruitment of inflammatory cells. Viral control was initially delayed; however, neither the kinetics of viral control nor viral persistence were affected. By contrast, the absence of Treg during the acute phase resulted in increased demyelination during viral persistence. These data suggest that CNS inflammation, progression of viral control and viral persistence are relatively independent of CD25(+)CD4(+) Treg. However, their absence during acute infection alters the ability of the host to limit tissue damage. PMID- 24210106 TI - The RNA-dependent RNA polymerase of Citrus tristeza virus forms oligomers. AB - The RNA-dependent RNA polymerases (RdRp) from Citrus tristeza virus (CTV) were tagged with HA and FLAG epitopes. Differentially tagged proteins were expressed either individually or concomitantly in Escherichia coli. Immunoprecipitation of the expressed proteins with anti-FLAG antibody followed by Western blot with anti HA antibody demonstrated that molecules of RdRp from CTV interact to form oligomers. Yeast two-hybrid assays showed that molecules of RdRp interact in eukaryotic cells. Co-immunoprecipitation with anti-FLAG antibody of truncated HA tagged RdRps (RdRpDelta1-166-HA, RdRpDelta1-390-HA, RdRp1-169-HA) co-expressed with full-length RdRp-FLAG showed that only RdRp1-169-HA interacted with the full length FLAG-RdRp. Yeast two-hybrid assays with truncated RdRp constructs confirmed that the oligomerization site resides in the N-terminal region and that the first 169 aa of CTV RdRp are necessary and sufficient for oligomerization both in bacterial and yeast cells. Development of control strategies targeting viral RdRp oligomer formation may inhibit virus replication and prove useful in control of CTV. PMID- 24210107 TI - Rice black-streaked dwarf virus P10 induces membranous structures at the ER and elicits the unfolded protein response in Nicotiana benthamiana. AB - Endoplasmic reticular (ER) membrane modifications play an important role in viral RNA replication and virion assembly but little is known about the involvement of ER-membrane remodeling in the infection cycle of fijiviruses in plant cells. The subcellular localization of Rice black-streaked dwarf virus outer capsid P10 was therefore examined using live-cell imaging. P10 fused to eGFP formed vesicular structures associated with ER membranes in Nicotiana benthamiana epidermal cells and in rice protoplasts. Subcellular fractionation experiments confirmed that P10 is an integral membrane protein. Three predicted transmembrane domains and two less-well-defined domains were each able to target eGFP to the ER. Disruption of the actin cytoskeleton with LatB, indicated that the maintenance of P10-induced membrane structures required the intact actin cytoskeleton. P10 induced the expression of ER stress marker genes, including ER stress-related chaperones and transcription factor, indicating that RBSDV P10 triggers ER stress and the unfolded protein response. PMID- 24210108 TI - Persistently adenovirus-infected lymphoid cells express microRNAs derived from the viral VAI and especially VAII RNA. AB - Human adenovirus can establish latent infections in lymphoid tissues in vivo and persistent, infections in cultured lymphoid cell lines. During lytic infection, adenovirus expresses microRNAs (miRNAs) derived from the viral non-coding RNAs VAI and, especially, VAII. Here, we demonstrate that persistently adenovirus infected human BJAB cells also produce adenovirus-derived miRNAs primarily derived from the viral VAII RNA, which contributes ~2.7% of all RNA-induced silencing complex (RISC)-associated RNAs. However, our data indicate that the 5' end of the predominant VAII-derived viral RNA, and hence its seed sequence, differs from what has been previously reported. Our data demonstrate that adenovirus expresses viral miRNAs in chronically infected lymphoid cells and raise the possibility that these may contribute to the maintenance of the latently adenovirus-infected lymphoid cells previously observed in mucosal associated lymphoid tissues in vivo. PMID- 24210109 TI - The spread of type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in North America: a phylogeographic approach. AB - The emergence and spread of Type 2 Porcine Reproductive and Respiratory Syndrome virus (Type 2 PRRSV) in North America is heavily influenced by the multiple site production system used in the hog industry. However, it is unclear how anthropogenic factors such has this have shaped the current spatial distribution of PRRSV genotypes. We employed Bayesian phylogeographic analyses of 7040 ORF5 sequences to reveal the recent geographical spread of Type 2 PRRSV in North America. The directions and intensities in our inferred virus traffic network closely mirror the hog transportation. Most notably, we reveal multiple viral introductions from Canada into the United States causing a major shift in virus genetic composition in the Midwest USA that went unnoticed by the regular surveillance and field epidemiological studies. Overall, these findings provide important insights into the dynamics of Type 2 PRRSV evolution and spread that will facilitate programs for control and prevention. PMID- 24210111 TI - AAVPG: a vigilant vector where transgene expression is induced by p53. AB - Using p53 to drive transgene expression from viral vectors may provide on demand expression in response to physiologic stress, such as hypoxia or DNA damage. Here we introduce AAVPG, an adeno-associated viral (AAV) vector where a p53-responsive promoter, termed PG, is used to control transgene expression. In vitro assays show that expression from the AAVPG-luc vector was induced specifically in the presence of functional p53 (1038+/-202 fold increase, p<0.001). The AAVPG-luc vector was an effective biosensor of p53 activation in response to hypoxia (4.48+/-0.6 fold increase in the presence of 250uM CoCl2, p<0.001) and biomechanical stress (2.53+/-0.4 fold increase with stretching, p<0.05). In vivo, the vigilant nature of the AAVPG-luc vector was revealed after treatment of tumor bearing mice with doxorubicin (pre-treatment, 3.4*10(5)+/-0.43*10(5)photons/s; post-treatment, 6.6*10(5)+/-2.1*10(5)photons/s, p<0.05). These results indicate that the AAVPG vector is an interesting option for detecting p53 activity both in vitro and in vivo. PMID- 24210110 TI - Gene expression profile regulated by the HPV16 E7 oncoprotein and estradiol in cervical tissue. AB - The HPV16 E7 oncoprotein and 17beta-estradiol are important factors for the induction of premalignant lesions and cervical cancer. The study of these factors is crucial for a better understanding of cervical tumorigenesis. Here, we assessed the global gene expression profiles induced by the HPV16 E7 oncoprotein and/or 17beta-estradiol in cervical tissue of FvB and K14E7 transgenic mice. We found that the most dramatic changes in gene expression occurred in K14E7 and FvB groups treated with 17beta-estradiol. A large number of differentially expressed genes involved in the immune response were observed in 17beta-estradiol treated groups. The E7 oncoprotein mainly affected the expression of genes involved in cellular metabolism. Our microarray data also identified differentially expressed genes that have not previously been reported in cervical cancer. The identification of genes regulated by E7 and 17beta-estradiol, provides the basis for further studies on their role in cervical carcinogenesis. PMID- 24210112 TI - Characterization of a chimeric foot-and-mouth disease virus bearing a bovine rhinitis B virus leader proteinase. AB - Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (L(pro) ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV L(pro) and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks L(pro), but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that L(pro) of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host. PMID- 24210113 TI - Characterizing monkeypox virus specific CD8+ T cell epitopes in rhesus macaques. AB - To characterize T cell epitopes in monkeypox virus (MPXV) infected rhesus macaques, we utilized IFNgamma Elispot assay to screen 400 predicted peptides from 20MPXV proteins. Two peptides from the F8L protein, an analog of E9L protein in vaccinia, were found to elicit CD8+ T cell responses. Prediction and in vitro MHC binding analyses suggest that one is restricted by Mamu-A1(*)001 and another by Mamu-A1(*)002. The Mamu-A1(*)002 epitope is completely identical in all reported sequences for variola, vaccinia, cowpox and MPXV. The Mamu-A1(*)001 epitope is conserved in MPXV and vaccinia, and has one residue substitution (V6>I) in some cowpox sequences and all variola sequences. Given CD8+ T-cell epitopes from E9L were also identified in humans and mice, our data suggested that F8L/E9L may be a dominant pox viral protein for CD8+ T cell responses, and may be considered as a target when designing vaccines that target pox-specific T cell responses. PMID- 24210115 TI - The baculovirus sulfhydryl oxidase Ac92 (P33) interacts with the Spodoptera frugiperda P53 protein and oxidizes it in vitro. AB - The Autographa californica M nucleopolyhedrovirus (AcMNPV) sulfhydryl oxidase Ac92 is essential for production of infectious virions. Ac92 also interacts with human p53 and enhances human p53-induced apoptosis in insect cells, but it is not known whether any relationship exists between Ac92 and native p53 homologs from insect hosts of AcMNPV. We found that Ac92 interacted with SfP53 from Spodoptera frugiperda in infected cells and oxidized SfP53 in vitro. However, Ac92 did not interact with or oxidize a mutant of SfP53 predicted to lack DNA binding. Silencing Sfp53 expression did not rescue the ability of an ac92-knockout virus to produce infectious virus. Similarly, ac92 expression did not affect SfP53 stimulated caspase activity or the localization of SfP53. Thus, although Ac92 binds to SfP53 during AcMNPV replication and oxidizes SfP53 in vitro, we could not detect any effects of this interaction on AcMNPV replication in cultured cells. PMID- 24210114 TI - Dynamic changes in viral population structure and compartmentalization during chronic hepatitis C virus infection in children. AB - Classic phylogenetic and modern population-based clustering methods were used to analyze hepatitis C virus (HCV) evolution in plasma and to assess viral compartmentalization within peripheral blood mononuclear cells (PBMCs) in 6 children during 3.2-9.6yr of follow-up. Population structure analysis of cloned amplicons encompassing hypervariable region 1 led to the distinction of two evolutionary patterns, one highly divergent and another one genetically homogeneous. Viral adaptability was reflected by co-evolution of viral communities switching rapidly from one to another in the context of divergence and stability associated with highly homogeneous communities which were replaced by new ones after long periods. Additionally, viral compartmentalization of HCV in PBMCs was statistically demonstrated, suggesting their role as a pool of genetic variability. Our results support the idea of a community-based structure of HCV viral populations during chronic infection and highlight a role of the PBMC compartment in the persistence of such structure. PMID- 24210116 TI - Coding potential of UL/b' from the initial source of rhesus cytomegalovirus Strain 68-1. AB - Rhesus cytomegalovirus (RhCMV) 68-1 is the prototypic strain of RhCMV that has been used for pathogenesis and vaccine development. We determined the complete sequence of the RhCMV 68-1 UL/b' region directly from the original urine from which RhCMV 68-1 was isolated in 1968, and compared it to other RhCMVs. The laboratory passaged RhCMV 68-1 has inversions, deletions, and stop codons in UL/b' that are absent in the original isolate and other low passage RhCMV isolates. Fourteen of the 17 open reading frames (ORFs) in 68-1 UL/b' in the original isolate share >95% amino acid identity with low passage RhCMV. The original isolate retains 6 ORFs that encode alpha-chemokine-like proteins, including RhUL146 and RhUL146b that share only 92% and 81% amino acid identity, respectively, with a contemporary low passage RhCMV isolate. Identification of the original RhCMV 68-1 UL/b' sequence is important for using RhCMV 68-1 in pathogenesis and vaccine studies. PMID- 24210117 TI - Cascade regulation of vaccinia virus gene expression is modulated by multistage promoters. AB - Vaccinia virus contains ~200 genes classified temporally as early, intermediate or late. We analyzed 53 intermediate promoters to determine whether any have dual late promoter activity. Our strategy involved (i) construction of a cell line that stably expressed the three late transcription factors, (ii) infection with a vaccinia virus mutant that expresses RNA polymerase but neither intermediate nor late transcription factors, and (iii) transfection with plasmids containing a luciferase reporter regulated by an intermediate promoter. After confirming the specificity of the system for late promoters, we found that many intermediate promoters had late promoter activity, the strength of which correlated with a TAAAT at the initiator site and T-content from positions -12 to -8 of the coding strand. In contrast, intermediate promoter activity correlated with the A-content from positions -22 to -14. The sequence correlations were confirmed by altering the specificities of strict intermediate and late promoters. PMID- 24210118 TI - Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo angiogenesis. AB - Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumor growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors. PMID- 24210119 TI - Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants. AB - In the present study we assessed pleiotropic characteristics of the antibody selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. PMID- 24210120 TI - Mitigation of variation observed in a peripheral blood mononuclear cell (PBMC) based HIV-1 neutralization assay by donor cell pooling. AB - Cultured primary peripheral blood mononuclear cells (PBMC) represent a potentially physiologic in vitro model of HIV-1 infection, but assessment of antibody-mediated HIV-1 neutralization using PBMC has been hindered by donor variability and lack of a sustainable individual PBMC source. To advance this model for HIV vaccine evaluation, intra- and inter-assay variability were assessed using monoclonal and polyclonal antibodies and PBMC targets from multiple HIV-seronegative donors. Inter-assay variability was introduced by using different PBMC for virus propagation, and more substantially, for assay targets. Neutralization titers varied by as much as 4 logs when using different individual donor PBMC as targets; variability was antibody-specific, with the greatest variation observed using an individual polyclonal plasma. Pooling of multiple PBMC donors significantly reduced median inter-assay variation to the level of intra-assay variation, suggesting a pathway forward for establishing a uniform, sustainable and standardized approach to the assessment of antibody function using a PBMC model. PMID- 24210121 TI - The product of SPO1 gene 56 inhibits host cell division during infection of Bacillus subtilis by bacteriophage SPO1. AB - Although cells of Bacillus subtilis continue to grow after being infected by bacteriophage SPO1, they do not undergo cell division. The product of SPO1 gene 56 is necessary and sufficient for this inhibition of cell division. GP56 inhibits cell division when expressed in uninfected B. subtilis, without preventing cell growth, DNA synthesis or chromosome segregation, ultimately causing filamentation and loss of viability. During infection, a gene 56 mutation prevents the inhibition of cell division that occurs in wild-type infection. Under the laboratory conditions used, the gene 56 mutation did not affect burst size, latent period, or other components of the host-takeover process. PMID- 24210122 TI - Engineered alphavirus replicon vaccines based on known attenuated viral mutants show limited effects on immunogenicity. AB - The immunogenicity of alphavirus replicon vaccines is determined by many factors including the level of antigen expression and induction of innate immune responses. Characterized attenuated alphavirus mutants contain changes to the genomic 5' UTR and mutations that result in altered non-structural protein cleavage timing leading to altered levels of antigen expression and interferon (IFN) induction. In an attempt to create more potent replicon vaccines, we engineered a panel of Venezuelan equine encephalitis-Sindbis virus chimeric replicons that contained these attenuating mutations. Modified replicons were ranked for antigen expression and IFN induction levels in cell culture and then evaluated in mice. The results of these studies showed that differences in antigen production and IFN induction in vitro did not correlate with large changes in immunogenicity in vivo. These findings indicate that the complex interactions between innate immune response and the replicon's ability to express antigen complicate rational design of more potent alphavirus replicons. PMID- 24210123 TI - Simian adenovirus type 35 has a recombinant genome comprising human and simian adenovirus sequences, which predicts its potential emergence as a human respiratory pathogen. AB - Emergent human and simian adenoviruses (HAdVs) may arise from genome recombination. Computational analysis of SAdV type 35 reveals a genome comprising a chassis with elements mostly from two simian adenoviruses, SAdV-B21 and -B27, and regions of high sequence similarity shared with HAdV-B21 and HAdV-B16. Although recombination direction cannot be determined, the presence of these regions suggests prior infections of humans by an ancestor of SAdV-B35, and/or vice versa. Absence of this virus in humans may reflect non-optimal conditions for zoonosis or incomplete typing, e.g., limited epitope-based. The presence of both a critical viral replication element found in HAdV genomes and genes that are highly similar to ones in HAdVs suggest the potential to establish in a human host. This allows a prediction that this virus may be a nascent human respiratory pathogen. The recombination potential of human and simian adenovirus genomes should be considered in the use of SAdVs as vectors for gene delivery in humans. PMID- 24210125 TI - Regulatory role of ASK1 in porcine circovirus type 2-induced apoptosis. AB - Porcine circovirus type 2 (PCV2), a major causative agent of postweaning multisystemic wasting syndrome which is an emerging and important swine disease, can induce apoptotic responses in vitro and in vivo. However, the molecular mechanism of PCV2-induced apoptosis is not well understood. Apoptosis signal regulating kinase 1 (ASK1), serves as an upstream enzyme that activates the JNK and p38 MAPK pathways, has been shown to play a target role in the regulation of apoptosis. Here, we showed that PCV2 infection induced ASK1 phosphorylation which preceded activation of JNK1/2 and p38 signaling in the cultured cells, and that the phosphatidylinostol 3-kinase (PI3K)/Akt signaling triggered by PCV2 infection limited the extent of JNK1/2 and p38 activation and thereby apoptotic cell death. Furthermore, inhibition of JNK and p38 activation is associated with PI3K dependent negative-regulation of ASK1 in the PCV2-infected cells. These results indicate an important regulatory role of ASK1 in PCV2-induced apoptotic responses. PMID- 24210124 TI - Immune targeting of PD-1(hi) expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques. AB - High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre ART levels, associated with decreased PD-1(hi) expressing T cells and Tregs in PBMCs, and PD-1(hi) Tregs in lymph nodes. It transiently decreased expression of Ki67 and alpha4beta7 in PBMC CD4(+) and CD8(+) Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1(hi) cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. PMID- 24210126 TI - A putative Rab-GTPase activation protein from Nicotiana benthamiana is important for Bamboo mosaic virus intercellular movement. AB - The cDNA-amplified fragment length polymorphism technique was applied to isolate the differentially expressed genes during Bamboo mosaic virus (BaMV) infection on Nicotiana benthamiana plants. One of the upregulated genes was cloned and predicted to contain a TBC domain designated as NbRabGAP1 (Rab GTPase activation protein 1). No significant difference was observed in BaMV accumulation in the NbRabGAP1-knockdown and the control protoplasts. However, BaMV accumulation was 50% and 2% in the inoculated and systemic leaves, respectively, of the knockdown plants to those of the control plants. By measuring the spreading area of BaMV infection foci in the inoculated leaves, we found that BaMV moved less efficiently in the NbRabGAP1-knockdown plants than in the control plants. Transient expression of the wild type NbRabGAP1 significantly increases BaMV accumulation in N. benthamiana. These results suggest that NbRabGAP1 with a functional Rab-GAP activity is involved in virus movement. PMID- 24210127 TI - Diversity of human papillomaviruses in skin lesions. AB - Pools of frozen biopsies from patients with squamous cell carcinoma (SCC) (n=29) actinic keratosis (AK) (n=31), keratoacanthoma (n=91) and swab samples from 84 SCCs and 91 AKs were analysed with an extended HPV general primer PCR and high throughput sequencing of amplimers. We found 273 different HPV isolates (87 known HPV types, 139 previously known HPV sequences (putative types) and 47 sequences from novel putative HPV types). Among the new sequences, five clustered in genus Betapapillomavirus and 42 in genus Gammapapillomavirus. Resequencing of the three pools between 21 to 70 times resulted in the detection of 283 different known or putative HPV types, with 156 different sequences found in only one of the pools. Type-specific PCRs for 37 putative types from an additional 296 patients found only two of these putative types. In conclusion, skin lesions contain a large diversity of HPV types, but most appeared to be rare infections. PMID- 24210128 TI - Retargeting of gene expression using endothelium specific hexon modified adenoviral vector. AB - Adenovirus serotype 5 (Ad5) vectors are well suited for gene therapy. However, tissue-selective transduction by systemically administered Ad5-based vectors is confounded by viral particle sequestration in the liver. Hexon-modified Ad5 expressing reporter gene under transcriptional control by the immediate/early cytomegalovirus (CMV) or the Roundabout 4 receptor (Robo4) enhancer/promoter was characterized by growth in cell culture, stability in vitro, gene transfer in the presence of human coagulation factor X, and biodistribution in mice. The obtained data demonstrate the utility of the Robo4 promoter in an Ad5 vector context. Substitution of the hypervariable region 7 (HVR7) of the Ad5 hexon with HVR7 from Ad serotype 3 resulted in decreased liver tropism and dramatically altered biodistribution of gene expression. The results of these studies suggest that the combination of liver detargeting using a genetic modification of hexon with an endothelium-specific transcriptional control element produces an additive effect in the improvement of Ad5 biodistribution. PMID- 24210131 TI - Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women. AB - Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10-12 gestational weeks recruited at a university hospital in Tokyo during 2009-2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3 phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) MUg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83-3.41 ng/dL, 0.01-27.4 MUIU/mL and 16.4-54.4 MUg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected. PMID- 24210132 TI - The genomics generation: heroes vs villains? PMID- 24210133 TI - It takes two: a brief report examining mutual support between parents and teens learning to drive. AB - Parental supervision of teen drivers has been identified as a way to mitigate teen crash risk. However, we know little about what motivates parents to be engaged supervisors throughout all phases of the learning-to-drive process. As a result, we are just beginning to understand what factors might motivate parents to actively supervise pre-license practice. In the current study, we examine how the provision of social support between parent and teen dyads might relate to parents' intention to remain engaged supervisors for the entire learner phase. Participants were a national sample of 309 teens with learner permits (age range 15-17 years, M (SD) 16.1 (0.8)) and a parent practice supervisor in the United States. Results indicated that parents in mutually supportive dyads reported stronger intentions to be engaged in their teens' practice driving over the course of the permit phase as compared to dyads where both members reported receiving low support: (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 2.02 [1.04, 3.94]; p=0.038). No benefit was observed for only having one member of the dyad provide support, irrespective of it being the parent or the teen. Future research on this topic should consider reciprocal parent-teen interactions as potential determinates of parent driving supervision behaviors. PMID- 24210134 TI - More than a decade of debates in the preeclampsia (island) workshops: a (personally biased) evolutionary perspective. AB - In this short remembrance paper, I survey (what I believe are) key events in the evolution of the concepts of preeclampsia from the first workshop in 1998 to the 2012 one, and from Tahiti to Reunion island, via Mauritius and Tioman Island. PMID- 24210135 TI - New insights into the role of perinatal HPA-axis dysregulation in postpartum depression. AB - Postpartum depression affects 10-20% of women following birth and exerts persisting adverse consequences on both mother and child. An incomplete understanding of its etiology constitutes a barrier to early identification and treatment. It is likely that prenatal hormone trajectories represent both markers of risk and also causal factors in the development of postpartum depression. During pregnancy the maternal hypothalamic-pituitary-adrenal axis undergoes dramatic alterations, due in large part, to the introduction of the placenta, a transient endocrine organ of fetal origin. We suggest that prenatal placental and hypothalamic-pituitary-adrenal axis dysregulation is predictive of risk for postpartum depression. In this model the positive feedback loop involving the systems regulating the products of the HPA axis results in higher prenatal levels of cortisol and placental corticotropin-releasing hormone. Greater elevations in placental corticotropin-releasing hormone are related to a disturbance in the sensitivity of the anterior pituitary to cortisol and also perhaps to decreased central corticotropin-releasing hormone secretion. Secondary or tertiary adrenal insufficiencies of a more extreme nature, which emerge during the prenatal period, may be predictive of an extended or more pronounced postpartum hypothalamic-pituitary-adrenal refractory period, which in turn represents a risk factor for development of postpartum depression. In addition to reviewing the relevant existing literature, new data are presented in support of this model which link elevated placental corticotropin-releasing hormone with low levels of ACTH at 3-months postpartum. Future research will further elucidate the role of hypothalamic-pituitary-adrenal axis dysregulation in postpartum depression and also whether prenatal placental and hypothalamic-pituitary-adrenal profiles might prove useful in the early identification of mothers at risk for postpartum mood dysregulation. PMID- 24210137 TI - Neuropeptides in learning and memory. AB - Dementia conditions and memory deficits of different origins (vascular, metabolic and primary neurodegenerative such as Alzheimer's and Parkinson's diseases) are getting more common and greater clinical problems recently in the aging population. Since the presently available cognitive enhancers have very limited therapeutical applications, there is an emerging need to elucidate the complex pathophysiological mechanisms, identify key mediators and novel targets for future drug development. Neuropeptides are widely distributed in brain regions responsible for learning and memory processes with special emphasis on the hippocampus, amygdala and the basal forebrain. They form networks with each other, and also have complex interactions with the cholinergic, glutamatergic, dopaminergic and GABA-ergic pathways. This review summarizes the extensive experimental data in the well-established rat and mouse models, as well as the few clinical results regarding the expression and the roles of the tachykinin system, somatostatin and the closely related cortistatin, vasoactive intestinal polypeptide (VIP) and pituitary adenylate-cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), opioid peptides and galanin. Furthermore, the main receptorial targets, mechanisms and interactions are described in order to highlight the possible therapeutical potentials. Agents not only symptomatically improving the functional impairments, but also inhibiting the progression of the neurodegenerative processes would be breakthroughs in this area. The most promising mechanisms determined at the level of exploratory investigations in animal models of cognitive disfunctions are somatostatin sst4, NPY Y2, PACAP-VIP VPAC1, tachykinin NK3 and galanin GALR2 receptor agonisms, as well as delta opioid receptor antagonism. Potent and selective non-peptide ligands with good CNS penetration are needed for further characterization of these molecular pathways to complete the preclinical studies and decide if any of the above described targets could be appropriate for clinical investigations. PMID- 24210138 TI - Role of neuropeptides in anxiety, stress, and depression: from animals to humans. AB - Major depression, with its strikingly high prevalence, is the most common cause of disability in communities of Western type, according to data of the World Health Organization. Stress-related mood disorders, besides their deleterious effects on the patient itself, also challenge the healthcare systems with their great social and economic impact. Our knowledge on the neurobiology of these conditions is less than sufficient as exemplified by the high proportion of patients who do not respond to currently available medications targeting monoaminergic systems. The search for new therapeutical strategies became therefore a "hot topic" in neuroscience, and there is a large body of evidence suggesting that brain neuropeptides not only participate is stress physiology, but they may also have clinical relevance. Based on data obtained in animal studies, neuropeptides and their receptors might be targeted by new candidate neuropharmacons with the hope that they will become important and effective tools in the management of stress related mood disorders. In this review, we attempt to summarize the latest evidence obtained using animal models for mood disorders, genetically modified rodent models for anxiety and depression, and we will pay some attention to previously published clinical data on corticotropin releasing factor, urocortin 1, urocortin 2, urocortin 3, arginine-vasopressin, neuropeptide Y, pituitary adenylate-cyclase activating polypeptide, neuropeptide S, oxytocin, substance P and galanin fields of stress research. PMID- 24210136 TI - CGRP and migraine: could PACAP play a role too? AB - Migraine is a debilitating neurological disorder that affects about 12% of the population. In the past decade, the role of the neuropeptide calcitonin gene related peptide (CGRP) in migraine has been firmly established by clinical studies. CGRP administration can trigger migraines, and CGRP receptor antagonists ameliorate migraine. In this review, we will describe multifunctional activities of CGRP that could potentially contribute to migraine. These include roles in light aversion, neurogenic inflammation, peripheral and central sensitization of nociceptive pathways, cortical spreading depression, and regulation of nitric oxide production. Yet clearly there will be many other contributing genes that could act in concert with CGRP. One candidate is pituitary adenylate cyclase activating peptide (PACAP), which shares some of the same actions as CGRP, including the ability to induce migraine in migraineurs and light aversive behavior in rodents. Interestingly, both CGRP and PACAP act on receptors that share an accessory subunit called receptor activity modifying protein-1 (RAMP1). Thus, comparisons between the actions of these two migraine-inducing neuropeptides, CGRP and PACAP, may provide new insights into migraine pathophysiology. PMID- 24210139 TI - Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: focus on davunetide (NAP). AB - This review focuses on the therapeutic effects and mechanisms of action of NAP (davunetide), an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP) which was discovered in our laboratory. We have recently described the effects of NAP in neurodegenerative disorders, and we now review the beneficial effects of NAP and other microtubule-stabilizing agents on impairments in axonal transport. Experiments in animal models of microtubule deficiency including tauopathy (spanning from drosophila to mammals) showed protection of axonal transport by microtubule-stabilizers and NAP, which was coupled to motor and cognitive protection. Clinical trials with NAP (davunetide) are reviewed paving the path to future developments. PMID- 24210140 TI - Polymorphic variation as a driver of differential neuropeptide gene expression. AB - The regulation of neuropeptide gene expression and their receptors in a tissue specific and stimulus inducible manner will determine in part behaviour and physiology. This can be a dynamic process resulting from short term changes in response to the environment or long term modulation imposed by epigenetically determined mechanisms established during life experiences. The latter underpins what is termed 'nature and nurture, or 'gene*environment interactions'. Dynamic gene expression of neuropeptides or their receptors is a key component of signalling in the CNS and their inappropriate regulation is therefore a predicted target underpinning psychiatric disorders and neuropathological processes. Finding the regulatory domains within our genome which have the potential to direct gene expression is a difficult challenge as 98% of our genome is non coding and, with the exception of proximal promoter regions, such elements can be quite distant from the gene that they regulate. This review will deal with how we can find such domains by addressing both the most conserved non-exonic regions in the genome using comparative genomics and the most recent or constantly evolving DNA such as repetitive DNA or retrotransposons. We shall also explore how polymorphic changes in such domains can be associated with CNS disorders by altering the appropriate gene expression patterns which maintain normal physiology. PMID- 24210141 TI - Neuropeptides in epilepsy. AB - Neuropeptides play an important role in modulating seizures and epilepsy. Unlike neurotransmitters which operate on a millisecond time-scale, neuropeptides have longer half lives; this leads to modulation of neuronal and network activity over prolonged periods, so contributing to setting the seizure threshold. Most neuropeptides are stored in large dense vesicles and co-localize with inhibitory interneurons. They are released upon high frequency stimulation making them attractive targets for modulation of seizures, during which high frequency discharges occur. Numerous neuropeptides have been implicated in epilepsy; one, ACTH, is already used in clinical practice to suppress seizures. Here, we concentrate on neuropeptides that have a direct effect on seizures, and for which therapeutic interventions are being developed. We have thus reviewed the abundant reports that support a role for neuropeptide Y (NPY), galanin, ghrelin, somatostatin and dynorphin in suppressing seizures and epileptogenesis, and for tachykinins having pro-epileptic effects. Most in vitro and in vivo studies are performed in hippocampal tissue in which receptor expression is usually high, making translation to other brain areas less clear. We highlight recent therapeutic strategies to treat epilepsy with neuropeptides, which are based on viral vector technology, and outline how such interventions need to be refined in order to address human disease. PMID- 24210143 TI - Comparison of whole-body MRI and skeletal scintigraphy for detection of bone metastatic tumors: a meta-analysis. AB - PURPOSE: We performed a meta-analysis to investigate and compare diagnostic performance of whole-body MRI and skeletal scintigraphy for detection of bone metastatic tumors. MATERIALS AND METHODS: PubMed and Embase were searched for relevant articles. We calculated sensitivities, specificities, diagnostic odds ratios (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and constructed summary receiver operating characteristic curves using bivariate models for whole-body MRI and skeletal scintigraphy, respectively. RESULTS: Across 7 studies (332 patients), whole-body MRI have similar patient-based sensitivity (0.84 vs 0.83), specificity (0.96 vs 0.94), DOR (137.0 vs 70.2), PLR (23.3 vs 13.0) and NLR (0.17 vs 0.19) with skeletal scintigraphy. Area under curves for whole-body MRI and skeletal scintigraphy was 0.94 and 0.89, respectively. CONCLUSION: Both whole-body MRI and skeletal scintigraphy have good diagnostic performance for detecting bone metastatic tumors. It remains inconclusive whether whole-body MRI or bone scintigraphy is superior in detecting bone metastatic tumors. PMID- 24210144 TI - Secretome of mesenchymal stem/stromal cells in regenerative medicine. PMID- 24210142 TI - Non-viral DNA delivery from porous hyaluronic acid hydrogels in mice. AB - The lack of vascularization within tissue-engineered constructs remains the primary cause of construct failure following implantation. Porous constructs have been successful in allowing for vessel infiltration without requiring extensive matrix degradation. We hypothesized that the rate and maturity of infiltrating vessels could be enhanced by complementing the open pore structure with the added delivery of DNA encoding for angiogenic growth factors. Both 100 and 60 MUm porous and non-porous hyaluronic acid hydrogels loaded with pro-angiogenic (pVEGF) or reporter (pGFPluc) plasmid nanoparticles were used to study the effects of pore size and DNA delivery on angiogenesis in a mouse subcutaneous implant model. GFP-expressing transfected cells were found inside all control hydrogels over the course of the study, although transfection levels peaked by week 3 for 100 and 60 MUm porous hydrogels. Transfection in non-porous hydrogels continued to increase over time corresponding with continued surface degradation. pVEGF transfection levels were not high enough to enhance angiogenesis by increasing vessel density, maturity, or size, although by 6 weeks for all pore size hydrogels more hydrogel implants were positive for vascularization when pVEGF polyplexes were incorporated compared to control hydrogels. Pore size was found to be the dominant factor in determining the angiogenic response with 60 MUm porous hydrogels having more vessels/area present than 100 MUm porous hydrogels at the initial onset of angiogenesis at 3 weeks. The results of this study show promise for the use of polyplex loaded porous hydrogels to transfect infiltrating cells in vivo and guide tissue regeneration and repair. PMID- 24210145 TI - Specialization and the current practices of general surgeons. AB - BACKGROUND: The impact of specialization on the practice of general surgery has not been characterized. Our goal was to assess general surgeons' operative practices to inform surgical education and workforce planning. STUDY DESIGN: We examined the practices of general surgeons identified in the 2008 State Inpatient and Ambulatory Surgery Databases of the Healthcare Cost and Utilization Project for 3 US states. Operations were identified using ICD-9 and CPT codes linked to encrypted physician identifiers. For each surgeon, total operative volume and percentage of practice that made up their most common operation were calculated. Correlation was measured between general surgeons' case volume and the number of other specialists in a health service area. RESULTS: There were 1,075 general surgeons who performed 240,510 operations in 2008. The mean operative volume for each surgeon was 224 annual procedures. General surgeons performed an average of 23 different types of operations. For the majority of general surgeons, their most common procedure constituted no more than 30% of total practice. The most common operations, ranked by the frequency they appeared as general surgeons' top procedure, included cholecystectomy, colonoscopy, endoscopy, and skin excision. The proportion of general surgery practice composed of endoscopic procedures inversely correlated with the number of gastroenterologists in the health service area (rho = -0.50; p = 0.005). CONCLUSIONS: Despite trends toward specialization, the current practices of general surgeons remain heterogeneous. This indicates a continued demand for broad-based surgical education to allow future surgeons to tailor their practices to their environment. PMID- 24210146 TI - In situ hypothermic perfusion with retrograde outflow during right hemihepatectomy: first experiences with a new technique. PMID- 24210147 TI - Cost effectiveness of mesh prophylaxis to prevent parastomal hernia in patients undergoing permanent colostomy for rectal cancer. AB - BACKGROUND: Parastomal hernia (PSH) is common after stoma formation. Studies have reported that mesh prophylaxis reduces PSH, but there are no cost-effectiveness data. Our objective was to determine the cost effectiveness of mesh prophylaxis vs no prophylaxis to prevent PSH in patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer. STUDY DESIGN: Using a cohort Markov model, we modeled the costs and effectiveness of mesh prophylaxis vs no prophylaxis at the index operation in a cohort of 60-year-old patients undergoing abdominoperineal resection for rectal cancer during a time horizon of 5 years. Costs were expressed in 2012 Canadian dollars (CAD$) and effectiveness in quality-adjusted life years. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In patients with stage I to III rectal cancer, prophylactic mesh was dominant (less costly and more effective) compared with no mesh. In patients with stage IV disease, mesh prophylaxis was associated with higher cost (CAD$495 more) and minimally increased effectiveness (0.05 additional quality-adjusted life years), resulting in an incremental cost-effectiveness ratio of CAD$10,818 per quality-adjusted life year. On sensitivity analyses, the decision was sensitive to the probability of mesh infection and the cost of the mesh, and method of diagnosing PSH. CONCLUSIONS: In patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer, mesh prophylaxis might be the less costly and more effective strategy compared with no mesh to prevent PSH in patients with stage I to III disease, and might be cost effective in patients with stage IV disease. PMID- 24210148 TI - Operative report teaching and synoptic operative reports: a national survey of surgical program directors. AB - BACKGROUND: Although operative report documentation (ORD) is an essential skill for surgeons and is evolving with electronic health records (EHRs), little is known about current ORD teaching in surgical training. STUDY DESIGN: An electronic survey was sent out in January 2012 to all 1,096 ACGME surgical program directors that assessed characteristics of training programs, EHR adoption, ORD education, synoptic or templated report usage for ORD, and attitudes and opinions about ORD education and electronic tools for ORD. Content thematic analysis of qualitative responses was performed iteratively until reaching saturation. RESULTS: Overall, 441 program directors (40%; 17.9 +/- 8.8 years in practice) responded from university-affiliated (383 [87%]), community/private (44 [10%]), and military (14 [3%]) programs. Although most (n = 295 [67%]) consider ORD teaching a priority, only 76 (17%) programs provide ORD instruction. Program directors formally trained in ORD were more likely to offer ORD instruction (61% vs 11%; p < 0.0001), as were obstetrics/gynecology programs (obstetrics/gynecology 35% vs surgery 18%, neurosurgery 16%, ophthalmology 14%, orthopaedics 14%; p < 0.05 each). Although EHR adoption and electronically available operative reports were common (91%), besides ophthalmology (31%) and obstetrics/gynecology (30%) programs, ORD with synoptic reporting was used in only 18% of programs overall. Program directors perceived major barriers to ORD instruction and synoptic reporting for ORD. CONCLUSIONS: Although most program directors consider ORD teaching an educational priority, incongruence exists between its perceived value and its adoption into surgical training. Operative report documentation with synoptic reporting is currently not common in most surgical subspecialties. PMID- 24210149 TI - Reduced postoperative chronic pain after tension-free inguinal hernia repair using absorbable sutures: a single-blind randomized clinical trial. AB - BACKGROUND: Chronic pain after inguinal hernia repair occurs in 16% to 62% of patients. The underlying mechanism probably involves sensory nerve damage and abnormal healing that might be influenced by the materials chosen for the procedure. We hypothesize that nonabsorbable sutures used for mesh fixation to the surrounding tissues are associated with higher rates of chronic groin pain after surgery. STUDY DESIGN: We conducted a single-blind randomized clinical trial to compare the effect of absorbable braided sutures (Vycril; Ethicon) and nonabsorbable monofilament sutures (Prolene; Ethicon) used in inguinal hernia repair on the rate of chronic pain. We assessed chronic pain using a 4-point verbal-rank scale during a 1-year postoperative follow-up period. RESULTS: Study groups included 100 patients in each group. No age, sex, or hernia-side differences were observed between the study groups. Chronic pain rate after surgery was higher in the nonabsorbable monofilament suture group compared with the absorbable braided suture group (37 vs 26 patients; p = 0.056). Time to pain disappearance was longer in the nonabsorbable monofilament suture vs the absorbable braided suture group (115.3 days; 95% CI, 88-142.7 vs 77.4 days; 95% CI, 54.3-100.3; p = 0.038, respectively). A 1-year age increment reduces the risk for chronic pain occurrence by 2.2% (odds ratio = 0.978%; 95% CI, 0.961-0.995; p = 0.013). The use of nonabsorbable sutures increases the risk for chronic pain in 94.9% compared with absorbable sutures (odds ratio = 1.949; 95% CI, 1.039-3.658; p = 0.038). CONCLUSIONS: Nonabsorbable suture use in inguinal hernia repair is associated with a higher rate of chronic pain and a longer time to pain disappearance as compared with absorbable sutures. PMID- 24210150 TI - [Focus on mediastinal Castleman disease]. AB - Castleman disease is a rare lymph nodes disease whose name covers different clinical presentations. The most frequent histology is the hyaline vascular localized form. In this case, Castleman disease occurs in young adults, and is localized to the mediastinum in one third of the cases. The disease is often asymptomatic, but paraneoplasic pemphigus has been described. The management of this form of Castleman disease is based on complete surgical resection. Perioperative immunomodulating treatments may be discussed in case of paraneoplasic pemphigus, mostly when affecting the bronchial tree. PMID- 24210151 TI - [Spontaneous bilateral chylothorax revealing a mediastinal and abdominal lymph node tuberculosis]. AB - Spontaneous chylothorax is a rare condition, lymph node tuberculosis is an exceptional etiology of chylothorax, we report an exceptional case of a patient with mediastinal and abdominal lymph node tuberculosis presenting with spontaneous bilateral chylothorax treated successfully by symptomatic medical treatment and antibacillary. PMID- 24210152 TI - [Role of pulmonary resections in management of multidrug-resistant tuberculosis. A monocentric series of 29 patients]. AB - INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a worldwide health problem. Surgery is often used as an adjuvent therapy with anti-tuberculosis agents. The aim of this study is to present our results of pulmonary resections in the treatment of MDR-TB. MATERIAL AND METHODS: [corrected] This is a retrospective monocentric study of 29 patients operated on between 1995 and 2010 for MDR-TB. RESULTS: Tuberculosis was evolving from 9 to 108 months with a median of 34.77+/-19.88 months. The average number of tuberculosis relapses was 2.73 per patient. All patients had a destroyed and/or cavitary parenchyma and 17 had bacilli in sputum at the time of surgery. Lobectomy (51.17%) and pneumonectomy (41.37%) were the main interventions carried out. The operative mortality was 3.44%. Complications such prolonged air leaking and empyema had occurred in 9 patients. The rate of postoperative microbiological conversion was 88.23%. One patient had a relapse 5 months after surgery. CONCLUSION: Surgery associated with medical treatment provides a high cure rate to the detriment of an acceptable morbidity and mortality. PMID- 24210153 TI - [First epidemiologic data on pneumonia in Cambodia]. AB - About 15% of deaths in adults are related to lung infections in Cambodia. Some knowledge on microbial epidemiology is crucial for deciding first-line antibiotic treatment. However, to date, these data are not available in Cambodia. Consequently, antibiotic prescription relies on French or neighborhood's countries guidelines, which are possibly not suitable. This cases-series aimed to provide data on microbial ecology in pneumonia. Medical charts of patients newly admitted for lung infection in the pulmonology unit of Preah Kossamak Hospital were retrospectively reviewed. Ninety-four patients were included and 29% had a complete microbiological diagnosis. Main germs isolated were: Gram-negative bacilli (n=20; 70.4%) and M. tuberculosis infections (n=7; 25.9%). There was one case of myeloidosis. No S. pneumonia was isolated, possibly due to sample shipping tropical conditions. Antibiograms showed high resistance profiles. Although this study bring new data in the field, it also showed that European guidelines for antibiotic are not relevant in such countries and stress the need for further dedicated and prospective studies. PMID- 24210154 TI - [Rendu-Osler-Weber syndrome. A case report]. PMID- 24210155 TI - [Pleural lymphatics and pleural diseases related to fibres]. AB - It is now well established that some pleural diseases, pleural plaques and malignant mesothelioma are related to asbestos fibre exposure although the mechanism of action of asbestos fibres is not fully understood. The development of artificial mineral fibres and carbon nanotubes, which share some morphological characteristics similar to asbestos fibres, is a present concern in the context of pleural diseases. Pleural plaques develop only in the parietal pleura, and in the 1990s, clinical observations have shown that the early development of mesothelioma also occurred on the parietal pleura. The peculiarity of the parietal pleura in contrast to the visceral pleura is the presence of "stomas" which are communication holes between the pleural cavity and the parietal pleura lymphatics. Morphological observations by thoracoscopy and experimental studies have shown that inhaled fibres translocate to the pleural space and, in human, are present in the parietal pleura at specific anthracotic areas (blackspots). Fibres accumulate on the stomas, up to block and locally induce an inflammatory reaction with cytokines release, that can be the bed of mesothelioma. However, despite the experimental data and observations in human pathology, the mechanisms of fibre translocation into the pleura is not yet clearly established. PMID- 24210156 TI - [Catamenial pneumothorax: easy to see, difficult to manage]. AB - INTRODUCTION: Catamenial pneumothorax (PNO) is a real clinical occurrence. Several cases are reported in the literature as a spontaneous PNO occurring during the catamenial period among women in their thirties. There is no consensus about management and the recurrence rate is very high whatever the initial treatment. PATIENTS AND METHODS: Among 310 cases of spontaneous PNO operated in our institution in 10 years, we identified five cases of catamenial PNO. A retrospective study of these cases was used to study the initial operating data, including the existence of intrathoracic lesions and the choice of technique of pleurodesis. Patient follow-up was clinically and radiologically. Adjuvant hormonal therapies, recurrence of PNO and treatment modalities have been studied. RESULTS: These five patients of average age 37.6 years (37,38) who had 2.6 (2.3) episodes of right catamenial PNO before hospitalization in surgery department. No patient was smoker. Two of them had a known thoracic or pelvic endometriosis. The initial surgery was video assisted thoracic surgery with a parietal pleurectomy and twice a mesh upon the diaphragm. There were no immediate postoperative complications, and the average length of stay was 6.6 days (5.9). Two patients had adjuvant hormonal therapy. All patients had at least one recurrence and three of them had redo surgery. CONCLUSION: The diagnosis of catamenial PNO must be mentioned in any woman who has a spontaneous pneumothorax right in catamenial period. Endometriosis should be systematically sought. A standardized therapeutic approach to establish the role of surgery and the most appropriate technique as well as the appropriateness and duration of peroperative hormonal therapy remains to be defined. PMID- 24210157 TI - [Cryptococcal infection and sarcoidosis: a coincidence?]. AB - INTRODUCTION: We report a case of cryptococcal infection that underwent in a patient with a medical history of asymptomatic sarcoidosis. This finding seems to be not incidental. CASE REPORT: A 35-years-old female was referred to hospital for a community-acquired pneumonia with pleural involvement. A physical examination showed a pleural syndrome. Chest imaging showed a parenchymal involvement with pleural effusion and numerous mediastinal nodes. Fiberoptic bronchoscopy revealed an obstruction of the right apical bronchus of the lower lobe. Biopsies and bronchoalveolar lavage confirmed a cryptococcal infection. The disease was considered as disseminated with a urinary and neurologic involvement. The outcome was fair under prolonged antifungal therapy. CONCLUSIONS: Cryptococcal infection is generally associated with immunosuppression. We suggest that sarcoidosis, although non symptomatic, may be a condition that promote the onset of cryptococcal infection. Even rare, cryptococcal infection is the most frequent opportunistic infection recorded with sarcoidosis patients. Histologic similarities between sarcoidosis and cryptococcal infection and the role of the macrophages which phagocyte the Cryptococcus neoformans are one of the hypothesis to assess these pathologic findings. A register is warranted to recover all opportunistic infection related to sarcoidosis in order to better understand the pathogeny. PMID- 24210158 TI - [Interest of collapse therapy in pulmonary extensively drug-resistant tuberculosis]. AB - Extensively drug-resistant (XDR) tuberculosis is rare in France. Treatment of XDR tuberculosis is difficult and therapeutic failures are frequent. Surgery is considered as one of the therapeutic options, but is of little use regarding its high morbi-mortality. We report successful treatment of a XDR tuberculosis case with a 21-month antibiotic regimen followed by a surgical collapse therapy because of persistence of a large cavity. No relapse was observed after five years. Surgery in the XDR tuberculosis treatment is discussed. PMID- 24210159 TI - [Metastatic thoracic lymph node carcinoma from extra-thoracic malignancy or from unknown primary site]. AB - Malignant mediastinal lymph nodes without pulmonary disease may be lymphomatous or the metastases from thoracic or extrathoracic malignancy. More rarely, metastatic lymph nodes are without primary site. Surgery is generally diagnostic, restricted to confirming the metastatic process, because of too numerous and disseminated or unresectable lymph nodes. Radical surgery consisting in lymphadenectomy can be effective in case of mediastinal lymph node malignancy without other extra- and intrathoracic disease. We observed in our experience and in several case reports long-term good results in such cases. We suggest that including surgery in the multimodality treatment of mediastinal metastatic lymph nodes may be advisable in selected patients. PMID- 24210160 TI - [Intrathoracic giant peripheral nerve sheath tumor during Von Recklinghausen disease]. AB - We report the case of a patient aged 23, admitted for bilateral intrathoracic tumor, including a giant right. Surgery was performed by right sternothoracotomy. After 7 days, she presented an irreversible cardiac arrest. The malignant peripheral nerve sheath tumors are rare and aggressive. Their incidence is 0.001% in the general population and 0.16% in patients with neurofibromatosis type 1. These tumors are characterized by their risk of recurrence and poor prognosis. The treatment is the surgical resection. We analyze incidence, diagnosis and prognosis of these tumors. PMID- 24210161 TI - Juvenile exposure to ketamine causes delayed emergence of EEG abnormalities during adulthood in mice. AB - BACKGROUND: Increased susceptibility to cognitive impairment or psychosis in adulthood is associated with adolescent drug abuse. Studies in adults have identified impairments in attention and memory, and changes in EEG, as common consequences of ketamine abuse. In contrast, the effects of ketamine on the juvenile brain have not been extensively tested. This is a significant omission, since abuse of ketamine is often observed within this age group. OBJECTIVES: Juvenile mice (4-6 weeks of age) were administered ketamine (20mg/kg) for 14 days. EEG was assessed in response to auditory stimulation both at one week following ketamine exposure at 7 weeks of age (juvenile) and again at 12 weeks of age (adult). EEG was analyzed for baseline activity, event-related power and event-related potentials (ERPs). RESULTS: While no effects of ketamine exposure were observed during the juvenile period, significant reductions in amplitude of the P20 ERP component and event-related gamma power were seen following ketamine when re-tested as adults. In contrast, reductions in event-related theta were seen in ketamine-exposed mice at both time points. CONCLUSIONS: Age related deficits in electrophysiological components such as P20 or event-related gamma may be due to an interruption of normal neural maturation. Reduction of NMDAR signaling during adolescence leads to delayed-onset disruption of gamma oscillations and the P20 component of the ERP. Further, delayed onset of impairment following adolescent ketamine abuse suggests that methods could be developed to detect and treat the early effects of drug exposure prior to the onset of disability. PMID- 24210162 TI - Substance use and substance use disorders in recently deployed and never deployed soldiers. AB - BACKGROUND: Military studies investigating the prevalence of substance use (SU) and substance use disorders (SUD) and the relation between SU and mental disorders often lack a comprehensive assessment of SU, SUD and mental disorders and comparable groups of deployed and non-deployed personnel. There is also limited data regarding SU and SUD in the German military to date. METHODS: Cross sectional examination of n=1483 soldiers recently deployed in Afghanistan and 889 never deployed soldiers using a fully-standardized diagnostic interview (MI-CIDI) including a comprehensive substance section. RESULTS: Across both groups, 12 months prevalence of DSM-IV alcohol use disorders was 3.1%, 36.9% reported binge drinking, 13.9% heavy drinking, 1.3% illegal drug use. 55.1% were regular smokers, 10.9% nicotine dependent. Although recently deployed soldiers revealed slightly higher rates in some measures, there were no significant differences to the never deployed regarding SU und SUD except that recently deployed soldiers smoked more cigarettes per day. The association of SU with mental mental disorders was substantially different though, revealing significant associations between SU and mental disorders only among recently deployed soldiers. CONCLUSIONS: We do not find remarkable differences in the prevalence of SU and SUD between recently deployed and never deployed soldiers. Especially binge drinking and regular smoking were prevalent across both samples indicating needs for improved interventions. The finding that SU and mental disorders are only associated in recently deployed soldiers might have implications for improved screening and prevention and suggests that deployment might promote different pathways and mechanisms involved in the evolution of SU and mental disorders. PMID- 24210163 TI - Tolerance and exhaustion: defining mechanisms of T cell dysfunction. AB - CD8 T cell activation and differentiation are tightly controlled, and dependent on the context in which naive T cells encounter antigen, can either result in functional memory or T cell dysfunction, including exhaustion, tolerance, anergy, or senescence. With the identification of phenotypic and functional traits shared in different settings of T cell dysfunction, distinctions between such dysfunctional states have become blurred. Here, we discuss distinct states of CD8 T cell dysfunction, with an emphasis on: (i) T cell tolerance to self-antigens (self-tolerance); (ii) T cell exhaustion during chronic infections; and (iii) tumor-induced T cell dysfunction. We highlight recent findings on cellular and molecular characteristics defining these states, cell-intrinsic regulatory mechanisms that induce and maintain them, and strategies that can lead to their reversal. PMID- 24210164 TI - Regulation of hematopoietic stem cells by bone marrow stromal cells. AB - Hematopoietic stem cells (HSCs) reside in specialized microenvironments (niches) in the bone marrow. The stem cell niche is thought to provide signals that support key HSC properties, including self-renewal capacity and long-term multilineage repopulation ability. The stromal cells that comprise the stem cell niche and the signals that they generate that support HSC function are the subjects of intense investigation. Here, we review the complex and diverse stromal cell populations that reside in the bone marrow and examine their contribution to HSC maintenance. We highlight recent data suggesting that perivascular chemokine CXC ligand (CXCL)12-expressing mesenchymal progenitors and endothelial cells are key cellular components of the stem cell niche in the bone marrow. PMID- 24210165 TI - Mayaro virus infection, Amazon Basin region, Peru, 2010-2013. AB - During 2010-2013, we recruited 16 persons with confirmed Mayaro virus infection in the Peruvian Amazon to prospectively follow clinical symptoms and serologic response over a 12-month period. Mayaro virus infection caused long-term arthralgia in more than half, similar to reports of other arthritogenic alphaviruses. PMID- 24210166 TI - The relationship between access to and use of dental services following expansion of a primary care service to embrace dental team training. AB - OBJECTIVES: To investigate changes in the patient population and treatment case mix within an expanded primary care dental training facility in Southern England. STUDY DESIGN: Cross-sectional analysis of patient management system data. METHOD: Electronic data for patients with a closed/completed treatment plan in the 12 month period prior to, and following, dental service expansion were extracted for analysis (n = 4343). Descriptive analysis involved age, sex, payment status, deprivation status and treatment activity. Logistic regression was used to model the likelihood of treatment involving laboratory constructed devices (crowns, bridges, dentures), in relation to demography and deprivation in each time period. RESULTS: The volume of patients using the service increased by 48.3% (1749 cf 2594). The average age increased from 31.97 (95%CI: 30.8, 32.5) to 36.4 years (95%CI: 35.6, 37.1); greatest increase was in the over 75 years age-group (96%). The patient base became less deprived: patients exempt from payment reduced from 43.2% (n = 755) to 28.6% (n = 741) (P = 0.001) and the mean population deprivation score (IMD) reduced from 24.5 (95%CI: 23.8, 25.2) to 22.3 (95%CI: 21.7, 22.8). The volume and proportion of care involving laboratory constructed devices increased from 8.3% (n = 145) to 15.8% (n = 411) whilst assessments without interventive care decreased (34.5%-26.3%). On a logistic regression, the odds of having treatment involving laboratory constructed devices, increased with increasing age in both time periods 7% (95% CI: 1.06 1.08) and 6% (95% CI: 1.05-1.07) respectively. Furthermore, the odds increased by 38% OR: 1.38 (95% CI: 1.01-1.89) in period 2, for white patients. After adjusting for these effects, the odds of having care that involved laboratory constructed devices were less in period 2 than period 1 (100% cf 43%) for those who were technically exempt from payment (OR = 2.0; 95% CI 1.34 to 2.90 cf, OR = 1.43; 95% CI 1.13-1.81). CONCLUSION: The patient population altered in relation to age and socio-economic status. The expanded service had greater uptake by older people while users were less likely to be deprived. The expanded service, free at the point of delivery, attracted a higher proportion of patients who would normally have to pay health service charges. The service also showed an increase in treatment case-mix that involved laboratory constructed dental devices. PMID- 24210167 TI - Supervised hybrid feature selection based on PSO and rough sets for medical diagnosis. AB - Medical datasets are often classified by a large number of disease measurements and a relatively small number of patient records. All these measurements (features) are not important or irrelevant/noisy. These features may be especially harmful in the case of relatively small training sets, where this irrelevancy and redundancy is harder to evaluate. On the other hand, this extreme number of features carries the problem of memory usage in order to represent the dataset. Feature Selection (FS) is a solution that involves finding a subset of prominent features to improve predictive accuracy and to remove the redundant features. Thus, the learning model receives a concise structure without forfeiting the predictive accuracy built by using only the selected prominent features. Therefore, nowadays, FS is an essential part of knowledge discovery. In this study, new supervised feature selection methods based on hybridization of Particle Swarm Optimization (PSO), PSO based Relative Reduct (PSO-RR) and PSO based Quick Reduct (PSO-QR) are presented for the diseases diagnosis. The experimental result on several standard medical datasets proves the efficiency of the proposed technique as well as enhancements over the existing feature selection techniques. PMID- 24210168 TI - Raw data extraction from electrocardiograms with Portable Document Format. AB - During the last two decades there has been a thorough research and development of standards and protocols in order to cope with different electrocardiogram formats from heterogeneous acquisition systems. Despite the efforts of public and private consortiums on creating a standardized electrocardiogram (ECG) storage format, there is still not a single one. Indeed, there is also the necessity of access to raw data of the ECGs previously acquired. Most of these documents have been saved as Adobe PDF files, since for medical staff it is an easy format for later visualization. However, this format presents difficulties when trying to access original raw data for subsequent studies and signal analysis. In this manner, this paper presents an application that obtains plain numerical data from ECG files stored with PDF format. Data can also be exported to one of the most common file formats in existence, to be easily accessed thereafter. PMID- 24210170 TI - Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings. AB - Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings. PMID- 24210169 TI - Behavioral effects of developmental methylmercury drinking water exposure in rodents. AB - Early methylmercury (MeHg) exposure can have long-lasting consequences likely arising from impaired developmental processes, the outcome of which has been exposed in several longitudinal studies of affected populations. Given the large number of newborns at an increased risk of learning disabilities associated with in utero MeHg exposure, it is important to study neurobehavioral alterations using ecologically valid and physiologically relevant models. This review highlights the benefits of using the MeHg drinking water exposure paradigm and outlines behavioral outcomes arising from this procedure in rodents. Combination treatments that exacerbate or ameliorate MeHg-induced effects, and possible molecular mechanisms underlying behavioral impairment are also discussed. PMID- 24210171 TI - Toxic and essential elements in children's blood (<6 years) from Kinshasa, DRC (the Democratic Republic of Congo). AB - In this study we determined the concentration of 9 trace elements (As, Cd, Cu, Hg, Mn, Mo, Pb, Se and Zn) in whole blood of children (n=100, 64 girls, 36 boys and median age: 36 months) using inductively coupled plasma mass spectrometry (ICP-MS). The proportion of children potentially deficient in essential elements or poisoned by toxic elements was evaluated. The aging effects on the concentration of these elements were also investigated. The median values were 3.17MUg/L (As), 0.15MUg/L (Cd), 1.1mg/L (Cu), 2.1MUg/L (Hg), 10.4MUg/L (Mn), 17.7MUg/L (Mo), 8.7MUg/dL (Pb), 10.7MUg/L (Se) and 5.0mg/L (Zn). The concentration of many elements (As, Cd, Hg, Mn, Pb and Zn) showed significant age variations but not sex influence. Regarding levels of the essential elements (Cu, Mn, Mo, Se and Zn), B-Cu, B-Mn, B-Se and B-Zn were in the normal range, whereas exceeded levels were observed for B-Mo. None of these children was deficient in essential elements. Except B-Cd, all toxic elements showed exceeded blood levels. The proportion of children potentially poisoned by toxic elements varies from 10% (n=10) to 95% (n=95) and depends on toxic element: 95% for As, 10% for Hg and 35% for Pb. The main health concerns emerging from this study are the high As, Hg and Pb exposures of the Kinshasan children requiring further documentation, corrective actions and the implementation of appropriate regulations. PMID- 24210172 TI - Braking BRAF: AMPK leaves ERK stranded in the desert. AB - In this issue, Shen et al. (2013) show that BRAF phosphorylation by AMPK attenuates BRAF signaling and inhibits cell proliferation. This identifies BRAF as a novel AMPK substrate and further reveals how these pathways interact. PMID- 24210173 TI - PAF makes it EZ(H2) for beta-catenin transactivation. AB - In this issue of Molecular Cell, Park and colleagues (Jung et al., 2013) show that PAF (PCNA-associated factor) binds to and hyperactivates transcriptional function of beta-catenin in colon cancer cells by recruiting EZH2 to the coactivator complex. PAF-beta-catenin and PAF-PCNA interactions are competitive, raising the question of whether beta-catenin might regulate PCNA-dependent DNA replication and repair. PMID- 24210174 TI - Linking the Enzymes that Unlink DNA. AB - Two papers in this issue, Castor et al. (2013) and Wyatt et al. (2013), and a third in Cell Reports, Garner et al. (2013), demonstrate that the scaffold protein SLX4 coordinates multiple nucleases in order to effectively resolve Holliday junctions and repair interstrand crosslinks (ICLs) in mammalian cells. PMID- 24210175 TI - Reality and practical aspects of healthcare to patients with inherited metabolic diseases in an adult nutrition unit. PMID- 24210176 TI - Are there healthy obese? AB - It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. PMID- 24210177 TI - Lantibiotics: promising candidates for future applications in health care. AB - The immense potential of bacteria for production of antimicrobials represents an inexhaustible source of new antibiotics. An emerging class of natural products is constituted by ribosomally synthesized and posttranslationally modified peptides (RiPPs). "Lantibiotics" (lanthionine and/or methyl-lanthionine containing antibiotics) belong to the earliest members of this class. The characteristic thioether amino acids are introduced into the precursor peptides by enzyme mediated posttranslational modifications. The encouraging antimicrobial activity of lantibiotics against multiresistant clinical pathogens, their stability against proteases, heat and oxidation make lantibiotics interesting candidates for novel antimicrobial applications in many areas of the healthcare sector and associated industries. In addition to applications as alternatives to classical antibiotics, lantibiotics can be used as probiotics, prophylactics or additives. Furthermore, the in vitro activity of the lantibiotic modification machinery opens the possibility to generate either improved synthetic lantibiotic peptides or to introduce thioether cross-links into existing therapeutics. PMID- 24210178 TI - [Bologna: a lost opportunity. The heterogeneity of Medical education in Spain]. PMID- 24210180 TI - Perception of acoustically presented time series with varied intervals. AB - Data from three experiments on serial perception of temporal intervals in the supra-second domain are reported. Sequences of short acoustic signals ("pips") separated by periods of silence were presented to the observers. Two types of time series, geometric or alternating, were used, where the modulus 1+delta of the inter-pip series and the base duration Tb (range from 1.1 to 6s) were varied as independent parameters. The observers had to judge whether the series were accelerating, decelerating, or uniform (3 paradigm), or to distinguish regular from irregular sequences (2 paradigm). "Intervals of subjective uniformity" (isus) were obtained by fitting Gaussian psychometric functions to individual subjects' responses. Progression towards longer base durations (Tb=4.4 or 6s) shifts the isus towards negative deltas, i.e., accelerating series. This finding is compatible with the phenomenon of "subjective shortening" of past temporal intervals, which is naturally accounted for by the lossy integration model of internal time representation. The opposite effect observed for short durations (Tb=1.1 or 1.5s) remains unexplained by the lossy integration model, and presents a challenge for further research. PMID- 24210181 TI - The occurrence of the filled duration illusion: a comparison of the method of adjustment with the method of magnitude estimation. AB - A time interval between the onset and the offset of a continuous sound (filled interval) is often perceived to be longer than a time interval between two successive brief sounds (empty interval) of the same physical duration. The present study examined whether and how this phenomenon, sometimes called the filled duration illusion (FDI), occurs for short time intervals (40-520 ms). The investigation was conducted with the method of adjustment (Experiment 1) and the method of magnitude estimation (Experiment 2). When the method of adjustment was used, the FDI did not appear for the majority of the participants, but it appeared clearly for some participants. In the latter case, the amount of the FDI increased as the interval duration lengthened. The FDI was more likely to occur with magnitude estimation than with the method of adjustment. The participants who showed clear FDI with one method did not necessarily show such clear FDI with the other method. PMID- 24210182 TI - The assessment of interpersonal pleasure: introduction of the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) and preliminary findings. AB - Although several valid measures of pleasure and anhedonia exist, there is a relative paucity of measures that adequately assess pleasure for social interactions. The Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) is a measure specifically designed to assess hedonic capacity for social and interpersonal pleasure. Various aspects of the validity and reliability of the ACIPS were examined in several ways. First, we assessed the factor structure as well as the internal consistency, convergent, and discriminant validity of the ACIPS in 496 young adults recruited from undergraduate classes. Second, we investigated the temporal stability of the measure by having a subset of the group return for retesting. Results from the factor analysis suggested a three factor model. The ACIPS was found to be highly reliable in terms of internal consistency and test-retest stability. Further, the ACIPS correlated in a theoretically meaningful way with other measures of pleasure and affect. The current research indicates that the ACIPS is a reliable and valid questionnaire to assess hedonic capacity for social and interpersonal pleasure in nonclinical samples. Suggestions for further clinical and research applications using the ACIPS are offered. PMID- 24210183 TI - Surgical complications after immediate nephrectomy versus preoperative chemotherapy in non-metastatic Wilms' tumour: findings from the 1991-2001 United Kingdom Children's Cancer Study Group UKW3 Trial. AB - PURPOSE: To compare surgical complication rates after immediate nephrectomy versus delayed nephrectomy following preoperative chemotherapy in children with non-metastatic Wilms' tumour enrolled in UKW3, both in randomised patients and in those for whom the treatment approach was defined by parental or physician choice. METHODS: Records for all patients enrolled into UKW3 were reviewed. Any record of tumour rupture or surgical complication was extracted and comparisons made between the two treatment strategies in both populations of randomised and non-randomised patients. RESULTS: Of 525 children enrolled, 205 patients were randomised to either immediate nephrectomy (n=103) or pre-operative chemotherapy followed by delayed nephrectomy (n=102). Of the 320 children not randomised, data were available on 189 cases treated with immediate nephrectomy and 103 treated with pre-operative chemotherapy. There were significantly fewer surgical complications in randomised children given pre-operative chemotherapy before surgery compared to children undergoing immediate nephrectomy (1% vs. 20.4%, P<0.001); this difference was most marked for tumour rupture (0% vs. 14.6%, P<0.001). CONCLUSIONS: Delayed nephrectomy for Wilms' tumour, preceded by pre operative chemotherapy was associated with fewer surgical complications compared with immediate nephrectomy. PMID- 24210184 TI - Association of E2F3 expression with clinicopathological features of Wilms' tumors. AB - PURPOSE: The transcription factor E2F3 plays an important role in controlling cell cycle progression and proliferation, and is overexpressed in various human cancers. The present study was undertaken to examine the expression of E2F3 and investigate its relevance in clinical and pathological features of pediatric Wilms' tumors. METHODS: Twenty-six Wilms' tumor samples collected at the First Affiliated Hospital of Harbin Medical University underwent immunohistochemical staining for E2F3 protein expression by measuring the percentage of E2F3-positive cells and integrated optical density (IOD), and quantitative real-time polymerase chain reaction (qRT-PCR) for E2F3 mRNA expression. RESULTS: The expression of E2F3 protein and mRNA was detectable in all the Wilms' tumor samples with big variations (The average percentage of positive cells was 30.2%+/-23.5%, range 0.3%-75.6%; average IOD was 6.61*10(4)+/-3.92*10(4), range 2.32*10(4) 13.84*10(4); average relative mRNA unit was 0.54+/-0.38, range 0.03-1.31), but not in fetal kidney tissues. Wilms' tumors with aggressive features, such as higher stage, unfavorable histology and higher risk level, expressed higher levels of E2F3 protein and mRNA. CONCLUSIONS: The preliminary data indicate that E2F3 is frequently expressed in pediatric Wilms' tumors examined in the present study. E2F3 expression may be associated with Wilms' tumors, particularly those that have more aggressive features. However, further studies are needed to validate these pilot observations and to clarify the functional and mechanistic significance of this association. PMID- 24210185 TI - Hepatocellular carcinoma in children: epidemiology and the impact of regional lymphadenectomy on surgical outcomes. AB - BACKGROUND: Factors influencing survival in children with HCC have not been studied. The objective of this study was to identify prognostic factors in pediatric HCC, and to determine whether regional lymphadenectomy is associated with improved survival. METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) registry. All patients <20 years old diagnosed with HCC from 1973-2009 were included. Disease-specific survival was compared using Kaplan-Meier statistics and Cox proportional-hazards regression. RESULTS: We identified 238 patients (139 Male: 99 Female). Overall, 112 (47%) received an operation (resection/transplantation). Observed mortality and adjusted hazard of disease-specific death was greater for females (HR=2.07, p=0.013) and older children. Among operative patients, 44% were documented to have a regional lymphadenectomy. Although demographic factors did not differ between lymphadenectomy and non-lymphadenectomy groups, patients who underwent lymphadenectomy had a greater proportion of metastatic disease (24% vs. 15%) and fibrolamellar HCC (53% vs. 31%). Five-year survival for lymphadenectomy patients was superior to non-lymphadenectomy (70% vs. 57%). Adjusted mortality for lymphadenectomy was also improved relative to non-lymphadenectomy (HR=0.26, p=0.013). CONCLUSIONS: HCC in children is associated with poor survival, especially among children older than 4 years and girls. In surgical candidates, regional lymphadenectomy may be associated with improved survival. PMID- 24210186 TI - Treatment of undifferentiated embryonal sarcoma of the liver in children--single center experience. AB - BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) represents less than 5% of all malignant hepatic tumors in childhood. It is considered an aggressive neoplasm with an unfavorable prognosis. The aim of this paper is to present a single center experience in the treatment of children with UESL. MATERIALS AND METHODS: Ten children with UESL were treated between 1981 and 2012. Age at diagnosis ranged from 4 months to 17 years (median age, 6 years and 9 months). Surgery after neoadjuvant chemotherapy (CHT) was performed in 7 patients, and in 3 patients primary surgery was done. Adjuvant chemotherapy was administered in all 10 patients (CYVADIC, CAV, CAV/ETIF/IF+ADM, CDDP/PLADO). Right hemihepatectomy was performed in 1 patient, extended right hemihepatectomy in 6, and partial resection of the right lobe (segments V-VI, segment V) in 2 patients. One patient with unresectable tumor affecting both lobes was listed for liver transplantation (LTx). RESULTS: Follow-up from diagnosis ranged from 50 to 222 months (mean 138 months). Among 9 patients treated with partial liver resection, distant metastases/local recurrence was not observed in any, and disease-free survival in this group is 100% (9 patients alive). The patient that underwent liver transplantation died of multiorgan failure 4 months postoperatively. However, this patient was misdiagnosed as having hepatoblastoma (HBL) and received PLADO chemotherapy. The overall survival rate is 90%. CONCLUSION: Excellent results with long-term survival can be achieved in children with UESL with conventional therapy, including a combination of neoadjuvant and adjuvant chemotherapy and surgery, even in large extensively growing tumors. PMID- 24210187 TI - Melanoma incidence rises for children and adolescents: an epidemiologic review of pediatric melanoma in the United States. AB - BACKGROUND/PURPOSE: This study was conducted to determine the influence of age on disease presentation and evaluate the change in pediatric melanoma incidence between 1998 and 2007. METHODS: We performed a retrospective review of all children <=18 years with cutaneous melanoma who were included in the 2007 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2007. RESULTS: We identified a total of 1447 patients with cutaneous melanoma. The overall average annual melanoma incidence was 5.4 per 1 million children and adolescents in the U.S., which increased throughout the study period. Most patients (89%) were at least 10 years of age (average age 15 years). Melanoma in situ (21%), thin (<1 mm) lesions (37%), stage I disease (46%), and superficial spreading histology (25%) were common at presentation. Only 1% of patients presented with distant metastases. Preadolescents younger than age 10 were ethnically more diverse and more likely to present with non truncal primaries and advanced disease (P<.01) compared to adolescents. CONCLUSIONS: The incidence of pediatric melanoma in the U.S. is increasing. There are significant differences between children and adolescents which suggest age based inherent differences in the biology of the disease may exist. PMID- 24210188 TI - First 24-h SNAP-II score and highest PaCO2 predict the need for ECMO in congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: Early clinical predictors for the use of ECMO in patients with congenital diaphragmatic hernia (CDH) are lacking. We sought to evaluate the first 24-h SNAP-II score and highest PaCO2 as predictors of ECMO support and in hospital mortality in neonates with CDH. METHODS: Retrospective review of 47 consecutive neonates with CDH admitted to our institution from January 2007 to December 2010 was performed. Covariates of ECMO use including SNAP-II score and highest PaCO2 within the first 24 h of NICU admission were evaluated. RESULTS: Of the 47 infants in this study, 24 patients were supported with ECMO. The ECMO group had a higher incidence of pulmonary hypertension, higher PaCO2, and higher 24-h SNAP-II scores. Only the SNAP-II score and not highest PaCO2 predicted mortality following multivariate adjustment. CONCLUSIONS: The first 24-h SNAP-II score and highest PaCO2 may provide some prognostic value in identifying neonates who undergo ECMO support; however neither measure was independently associated with the use of therapy. Only the SNAP-II score was associated with in-hospital mortality following multivariate adjustment. Additional study is needed to validate these results in a larger data set. PMID- 24210189 TI - Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia. AB - BACKGROUND/PURPOSE: Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. METHODS: Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. RESULTS: Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050+/-0.01 vs. 0.3125+/-0.01; P<.0001) and with CDH (0.1671+/-0.01 vs. 0.3125+/-0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. CONCLUSION: Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. PMID- 24210190 TI - Octreotide for chylous effusions in congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: Chylothorax is a frequent complication in congenital diaphragmatic hernia (CDH) infants and is associated with significant morbidity. The optimal treatment strategy remains unclear. We hypothesize that octreotide decreases chylous effusions in infants with CDH. METHODS: This is a retrospective study of all infants with CDH admitted to our institution from October 2006 to October 2011. RESULTS: Eleven (12%) infants developed a chylothorax. Five infants were managed conservatively with thoracostomy and total parenteral nutrition. Six infants were started on octreotide therapy. None of the infants required surgical intervention to stop the effusion. There was no significant difference in survival to discharge, length of stay, or average daily chest tube output between groups. There appeared to be a temporally associated drop in chest tube output upon initiation of octreotide in two infants; however, the overall rate of decline in chest tube drainage was unchanged. In addition, there were infants in the conservative group who demonstrated a similar drop in daily chest tube output despite the absence of octreotide. CONCLUSIONS: Our data suggest that the majority of chylous effusions in CDH infants resolve with conservative therapy alone. PMID- 24210191 TI - Fluoroscopic balloon dilatation for caustic esophageal stricture in children: an 8-year experience. AB - PURPOSE: Esophageal balloon dilatation (EBD), when performed early and correctly, can efficiently treat caustic esophageal stricture (ES). Herein, we present 8 years of experience treating caustic ES, and discuss the technique as well as the complications. METHODS: We retrospectively reviewed the medical records of 38 children in whom we performed fluoroscopic EBD under general anesthesia for caustic ES between November 2004 and November 2012 in our hospitals. The patients were grouped into the early dilatation group, who began EBD earlier (mean, 15 days) after caustic ingestion, and the late dilatation group who was referred later (mean, 34 days) for EBD by other centers. The ESs were classified into short and long strictures. Balloon size was increased gradually to a sufficient diameter over consecutive sessions. Characteristics of patients and ES, details of the EBD, and treatment results were analyzed. RESULTS: A total of 369 EBD sessions were successfully performed in 38 children (aged 14 months to 14 years, median 3.5 years). In six patients, EBD treatments are continuing, one patient was lost to follow up, one patient who received a stent was excluded, and three returned to their previous centers. The remaining 27 patients were treated successfully by repeated EBD treatments. Nevertheless, in the early dilatation group (n=16), EBD treatment was significantly faster and shorter than that in the late dilatation group (n=11). In addition, the short stricture treatment was also of significantly shorter duration than the long stricture treatment. Six (1.6%) esophageal perforations occurred in five patients (13.2%); all were treated conservatively. There was no mortality. CONCLUSIONS: For treatment of caustic ES, fluoroscopically guided EBD is safe and has a low rate of complications as well as a 100% success rate. However, it should be begun earlier, and in children, should be performed gently with balloons of gradually increasing appropriate diameters over consecutive sessions. PMID- 24210192 TI - The use of retrievable fully covered self-expanding metal stent in refractory postoperative restenosis of benign esophageal stricture in children. AB - PURPOSE: This study analyzes the efficacy and safety of a retrievable, fully covered self-expanding metal stent (cSEMS) in the treatment of refractory benign esophageal restenosis in children. METHODS: This is a retrospective analysis of the application of a newly designed cSEMS in treating refractory benign postoperative restenosis in five children with ages ranging from 16 months to 8 years. Efficacy and safety were evaluated during the follow-up period. RESULTS: cSEMS with or without an antireflux valve at the distal end were successfully placed and removed in five children. These five patients were followed up for 4 12 months after stent removal. Among the five patients, ulcerative stricture was observed in two patients because of reflux esophagitis, while three patients showed no signs of stricture recurrence. Stent migration was observed in three patients, two of which required the stent to be reset. The narrow esophagus was successfully expended to a diameter of 12-13 mm. Besides the observation of mild granulation tissue growth in one case, no severe complications were observed during surgery and after stent placement. CONCLUSION: Our study suggests that a retrievable, fully covered SEMS is safe and partially effective for treating refractory benign postoperative esophageal restenosis in children during short term observation. PMID- 24210193 TI - A standardised investigative strategy prior to revisional oesophageal surgery in children: High incidence of unexpected findings. AB - BACKGROUND/PURPOSE: Revisional oesophageal reconstructive surgery carries uncommon and unusual risks related to previous surgery. To provide maximum anatomical detail and facilitate successful outcome, we report a standardised pre operative investigative strategy for all such patients. METHODS: Prospective 8 month cohort study following the introduction of this strategy. All patients underwent high resolution thoracic contrast CT scan and micro-laryngo bronchoscopy by a paediatric ENT surgeon in addition to upper gastrointestinal contrast study, oesophagoscopy, and echocardiogram. RESULTS: Seven children (median age 5.6 months [range 2.2-60]) completed the pathway. Four were referred with recurrence of a previously divided tracheo-oesophageal fistula (3 congenital, 1 acquired) and 3 (all with oesophagostomy) for oesophageal replacement for congenital isolated oesophageal atresia (OA, n=1) and failed repair of OA with distal TOF with wide gap (n=2). Overall, unanticipated findings were demonstrated in 6/7 children and comprised severe tracheomalacia and right main bronchus stenosis requiring aortopexy (n=1), vocal cord palsy (n=2), extensive mediastinal rotation (n=1), proximal tracheal diverticulum (n=1), severe subglottic stenosis requiring airway reconstruction (n=1), proximal tracheal diverticulum (n=1), right sided aortic arch (n=1) and left sided aortic arch (previously reported to be right sided, n=1). CONCLUSIONS: This standardised approach for this complex group of patients reveals a high incidence of unexpected anatomical and functional anomalies with significant surgical and possible medico-legal implications. We recommend these investigations during the pre-operative work-up prior to all revisional oesophageal surgery. PMID- 24210194 TI - Pepsin levels and oxidative stress markers in exhaled breath condensate of patients with gastroesophageal reflux disease. AB - AIM: To evaluate the pepsin and oxidative stress markers in exhaled breath condensate (EBC) in patients with gastroesophageal reflux disease (GERD). PATIENTS AND METHOD: Patients with a presumptive diagnosis of GERD with recurrent respiratory and gastrointestinal problems aged between 2 and 14 years were included in the study. All patients underwent pH monitoring. Patients with a reflux index (RI) >=4 were assessed as the reflux group, and those with an RO <4 were assessed as the non-reflux group. Pepsin levels and oxidative stress markers [NO metabolites (NOX) and total sulphydrile (TSH) levels] were measured in the EBC. RESULTS: There were 24 patients in the reflux group [RI 17.6 (6.6-46.4)] [median, interquartile range] and 23 in the non-reflux group [RI 0.8 (0.5-1.9) (p<0.001). Pepsin levels in the EBC were below the level of detection. The median levels of NOx in the EBC of children with reflux [13.7 MUmol/L (7.3-24.5)] were lower in than non-reflux group [21.0 MUmol/L (14.0-25.2)] (p=0.034). There was a negative correlation between reflux index and NOX levels in EBC (rs: -0.331, p=0.023). In contrast, there was no difference in TSH levels between the reflux and non-reflux groups [37.4 MUmol/L (30.2-44.6) vs 40.1 MUmol/L (37.4-44.9), respectively, (p>0.05)]. CONCLUSION: Decreased levels of NOX in patients with GER disease suggest increased oxidative stress in airways of these patients. PMID- 24210195 TI - Effect of delivery approach on outcomes in fetuses with gastroschisis. AB - BACKGROUND/PURPOSE: There is considerable controversy regarding optimal mode and timing of delivery for fetuses with gastroschisis. Our objectives were to describe the variation in institutional approach regarding these factors, and to evaluate the effect of timing of delivery on outcomes in fetuses with gastroschesis. METHODS: Members of the maternal-fetal medicine community across Canada were surveyed regarding their personal and institutional approach of delivery. Data from the Canadian Pediatric Surgery Network (CAPSnet) were analyzed. RESULTS: The survey showed significant variability in delivery approach between institutions, although no center routinely performs cesarean section. Infants delivered vaginally (VD) were categorized into three groups: Group 1, VD <36 weeks (n=114); Group 2, VD 36-37 weeks (n=218); and Group 3, VD >=38 weeks (n=75). Score of Neonatal Acute Physiology, complication rates, length of time on total parenteral nutrition (TPN), and length of hospital stay (LOS) were higher in Group 1; bowel matting was greater in Group 3. There were no differences between the groups regarding other complications. CONCLUSIONS: Our data suggest that preterm delivery was associated with more complications, longer time on TPN, and longer LOS; delivery >=38 weeks was associated with increased bowel matting. These outcomes should be considered when determining institutional protocol. PMID- 24210196 TI - Intracranial anomalies and cloacal exstrophy--is there a role for screening? AB - BACKGROUND/PURPOSE: Cloacal exstrophy (CE) is a severe multi-system congenital defect. While spina bifida is a defining feature of cloacal exstrophy, patients are not routinely screened for intracranial anomalies (ICAs). We sought to better characterize this risk of ICA in the CE patient. METHODS: We retrospectively reviewed the medical records of 81 children with CE treated at our institution, identifying intracranial pathology, including hydrocephalus, Chiari malformation and craniosynostosis. Data points included ICA, neural tube defect, surgical procedures, and ambulatory status. RESULTS: Of the 39 patients with cranial imaging, 31% had an ICA: 6 hydrocephalus, 3 Chiari malformation, 1 craniosynostosis, 1 hydrocephalus and craniosynostosis, and 1 Chiari malformation and craniosynostosis. All patients with ICAs had spina bifida. Patients with ICAs underwent more neurosurgical procedures, including more spinal procedures. Patients with ICAs were much more likely to be wheelchair-bound or ambulate minimally when compared to patients without anomalies. CONCLUSION: In our population of CE patients with available head imaging, 31% had an ICA, thus screening would seem prudent. As all patients with ICAs had spina bifida, it may be less important to screen those rare CE patients without spinal pathology. Patients with ICAs were more likely to be wheelchair-bound, suggesting worse neurologic outcomes. PMID- 24210197 TI - Median arcuate ligament syndrome in the pediatric population. AB - OBJECTIVES: Median arcuate ligament syndrome (MALS) is a vascular compression syndrome with symptoms that overlap chronic functional abdominal pain (CFAP). We report our experience treating MALS in a pediatric cohort previously diagnosed with CFAP. PATIENTS AND METHODS: We prospectively evaluated 46 pediatric (<21years of age) patients diagnosed with MALS at a tertiary care referral center from 2008 to 2012. All patients had previously been diagnosed with CFAP. Patients were evaluated for celiac artery compression by duplex ultrasound and diagnosis was confirmed by computed tomography. Quality of life (QOL) was determined by pre and postsurgical administration of PedsQLTM questionnaire. The patients underwent laparoscopic release of the median arcuate ligament overlying the celiac artery which included surgical neurolysis. We examined the hemodynamic changes in parameters of the celiac artery and perioperative QOL outcomes to determine correlation. RESULTS: All patients had studies suggestive of MALS on duplex and computed tomography; 91% (n=42) positive for MALS were females. All patients underwent a technically satisfactory laparoscopic surgical release resulting in a significant improvement in blood flow through the celiac artery. There were no deaths and a total of 9 complications, 8 requiring a secondary procedure; 33 patients were administered QOL surveys. 18 patients completed the survey with 15 (83%) patients reporting overall improvement in the QOL. Overall, 31/46 patients (67%) reported improvement of symptoms since the time of surgery. CONCLUSIONS: MALS was found to be more common in pediatric females than males. Laparoscopic release of the celiac artery can be performed safely in the pediatric population. Surgical release of the artery and resultant neurolysis resulted in significant improvement in the blood flow, symptoms, and overall QOL in this cohort. The overall improvement in QOL outcome measures after surgery leads us to conclude that MALS might be earlier diagnosed and possibly treated in patients with CFAP. We recommend a multidisciplinary team approach to care for these complex patients. PMID- 24210198 TI - Modified Puestow procedure for the management of chronic pancreatitis in children. AB - PURPOSE: To present our experience with the modified Puestow procedure in the management of children with chronic pancreatitis. METHODS: Retrospective chart review of patients treated between 2003 and 2012. RESULTS: Six patients underwent a modified Puestow procedure (lateral pancreaticojejunostomy) for the management of chronic pancreatitis, three females and three males. Four patients had hereditary pancreatitis (three with confirmed N34S mutation in the SPINK1 gene), one patient had chronic pancreatitis of unknown etiology, and one patient with annular pancreas developed obstructive chronic pancreatitis. The pancreatic duct was dilated in all cases, with a maximum diameter of 5 to 10mm. Median time between onset of pain and surgery was 4 years (range: 1-9). Median age at surgery was 7.5 years (range: 5-15). Median hospital stay was 12 days (range: 9-28). Median follow up was 4.5 years (range: 5 months to 9 years). All patients had temporary postoperative improvement of their abdominal pain. In two patients the pain recurred at 6 months and 2 years postoperatively and eventually required total pancreatectomy to treat intractable pain, 3 and 8 years after surgery. Two patients were pain free for two years and subsequently developed occasional episodes of pain. The two most recent patients are pain free at 1 year (obstructive chronic pancreatitis) and 5 months (hereditary pancreatitis) follow up. Two patients developed type I diabetes mellitus 10 and 12 months postoperatively (one with hereditary and one with idiopathic chronic pancreatitis). CONCLUSION: We conclude that the modified Puestow procedure in children is feasible and safe. It seems to provide definitive pain control and prevent further damage to the pancreas in patients with obstructive chronic pancreatitis. However, in patients with hereditary pancreatitis, pain control outcomes are variable and the operation may not abrogate the progression of disease to pancreatic insufficiency. PMID- 24210199 TI - Implementation of laparoscopic splenectomy in children and the incidence of portal vein thrombosis diagnosed by ultrasonography. AB - BACKGROUND: The aim of this study is to evaluate if symptomatic or asymptomatic PVT, as diagnosed with ultrasonography (US), occurs more often in children after the introduction and implementation of LS compared to open splenectomy. METHODS: A retrospective cohort of 76 splenectomized patients for benign hematological disease were analyzed, 24 after open splenectomy (OS) and 52 after LS. RESULTS: In six of the OS and 40 after LS a postoperative US was obtained. In two patients after LS, a PVT was seen on US. Both patients were symptomatic and also underwent a laparoscopic cholecystectomy. The length of stay in the hospital was significantly shorter for LS (median 4.5 days, range 2-12) compared to OS (median 7 days, range 5-12), (P=.00). Median operation time of OS was 65 min (range 35 130 min) and of LS 170 min (range 85-275 min) (P=.00). There was no difference in postoperative complications. CONCLUSION: The risk of developing a PVT after laparoscopic splenectomy seems low, and thus LS is not contraindicated in patients with benign hematological disease. When combining LS and laparoscopic cholecystectomy, prophylactic heparin might be considered. PMID- 24210200 TI - The research on screening differentially expressed genes in Hirschsprung's disease by using Microarray. AB - OBJECTIVE: To study the differential expression of genes between Hirschsprung's disease (HSCR) and normal tissue by using microarray for exploring the mechanism of HSCR development and establishing the gene expression profiles of HSCR. METHODS: Colon tissues (aganglionic and normal segments) of 4 patients with HSCR were detected by the Agilent SurePrint G3 Human GE 8x60K Microarrays. RT-PCR was used to verify the results of Microarray test. Then, immunohistochemistry was used to demonstrate the expression of HAND2 in the myenteric plexus of the colon from 46 patients with HSCR to further explore the relationship between HAND2 and development of HSCR. RESULTS: A total of 12,125 meaningful expressed genes were screened out. 4 pairs of specimens had 622 differentially expressed genes, 584 (93.89%) of which were up-regulated while 38(6.11%) were down-regulated. 6 of the 622 genes were tested by RT-PCR, which were consistent with the results detected by Microarray. The average optical density of positive expression of HAND2 in myenteric plexus was compared between the aganglionic, transitional, dilated, normal segments and control group. The average optical density in the aganglionic segments was obviously reduced. Statistical analyzed data showed that it has significant deviation (P<0.01). CONCLUSION: 1. A set of differentially expressed genes between aganglionic and normal segments of HSCR was obtained. Our data may provide significant information to research the pathogenesis of HSCR. 2. Reduced protein expression of HAND2 in the myenteric plexus of the aganglionic would suggest that HAND2 was involved in the pathogenesis of HSCR. PMID- 24210201 TI - Transanal, full-thickness, Swenson-like approach for Hirschsprung disease. AB - PURPOSE: Swenson's procedure for Hirschsprung disease (HD) was thought to disturb fecal, urinary, and ejaculatory functions leading to other approaches including the Soave and Duhamel techniques. Given our Center's experience with a full thickness rectal dissection for anorectal malformations, and using the new transanal concept, we chose to apply these ideas to the primary treatment of HD, and describe technical aspects and impact on fecal, urinary, and sexual function. METHODS: We reviewed our series of HD patients who underwent a transanal, Swenson like rectosigmoid dissection, assessing for postoperative stricture, anastomotic leak, enterocolitis, and long-term results for bowel, urinary, and sexual function. RESULTS: Of 67 patients, 28 had a transanal resection, 5 had transanal plus laparoscopy, and 34 had transanal plus laparotomy, of those, 28 patients had a leveling colostomy prior to referral. The average length of resection was 27 cm +/- 12.7 cm. Mean follow-up was 17.2 months (range 1-96 months). 44 patients were at least three years old at follow-up and were assessed for urinary and fecal continence; all (100%) had voluntary bowel movements and urinary continence. Enterocolitis occurred in 9 patients (14%) and constipation (requiring laxatives) occurred in 21 (32%). Of 24 male patients, 21 (88%) reported the occurrence of spontaneous erections post-operatively. CONCLUSION: Our data support the fact that a modification of Swenson's original transabdominal dissection concept using the recently described transanal approach is an excellent technique for Hirschsprung, and produces excellent long-term outcomes for fecal and urinary continence, and seems to preserve erectile function. PMID- 24210202 TI - The role of a colon resection in combination with a Malone appendicostomy as part of a bowel management program for the treatment of fecal incontinence. AB - PURPOSE: Surgical options previously described by us as part of a bowel management program for the treatment of soiling and fecal incontinence include (1) resection of a megarectosigmoid to reduce a patient's laxative requirement or (2) a Malone appendicostomy in patients who require enemas. We have found that some patients may benefit from both procedures. METHODS: We reviewed 18 fecally incontinent patients with structural or functional disorders of the anorectosigmoid (16 ARM, 1 spina bifida, and 1 SCT) who underwent both procedures. RESULTS: Of 18 patients, the enema regimen prior to resection had an average volume of 681 ml of saline (Range 400-1000 ml) and 60 ml (Range 48-117 ml) of additives (glycerine, castile soap and/or phosphate). Following the colon resection, the average volume of saline and additives was 335 ml (Range 130-650 ml) and 25 ml (Range 0-60 ml), respectively, a 50% reduction for both (P<0.01). The time for enema administration and evacuation was reduced by 25%, and the enemas were more effective, rendering the patients clean in 18 of 18 cases (follow-up was 3 months to 21 years). 2 patients later demonstrated that they could be managed with laxatives alone. CONCLUSION: In patients with poor continence potential and a megarectosigmoid, combining a colon resection with a Malone appendicostomy can make the enema more effective. In some rare cases we found the resection may allow for a better response to laxatives. PMID- 24210203 TI - Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula feeding only neonatal rat model of necrotizing enterocolitis. AB - INTRODUCTION: The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC). MATERIAL AND METHODS: Newborn Sprague-Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression. RESULTS: The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p<0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1. DISCUSSION: Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease. PMID- 24210204 TI - Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis. AB - BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC. METHODS: The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/re-oxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified, and the transcriptome was analyzed using microarray. RESULTS: We found several TJ genes such as claudins 1, 8, 14, 15, and gap junction protein to be affected. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC. CONCLUSION: This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC. PMID- 24210205 TI - Assessing quality in pediatric surgery--the limited role of appendectomy as the optimal target. AB - BACKGROUND: Appendectomy is one of the highest volume procedures in children performed across a variety of hospital types in the U.S. potentially making it the ideal procedure to target when assessing hospital and surgeon quality. Though appendiceal perforation rate has been identified as a potential quality target reflecting primary care access, perforation rates have little association with hospital or surgeon quality. The utility and reliability of appendectomy as a target procedure to judge hospital quality based on outcomes beyond perforation rates are unknown. METHODS: Using the 2008 Nationwide Inpatient Sample, hospital pediatric appendectomy volumes were determined. Based on literature review, a variety of complication rate thresholds to identify hospital outlier status were determined using sample size calculations. The percent of U.S. hospitals that could exceed volume thresholds in order to be reliably compared was determined. RESULTS: Several complication rates of interest were identified ranging from mortality at 0.19% to a composite overall morbidity at 6.44%. Minimum hospital caseloads required to detect a doubling of complication rates included 127 cases for a composite overall morbidity, 276 cases for wound infection, 285 cases for negative appendectomy, 335 cases for intra-abdominal abscess, 438 cases for postoperative ileus, and 4,729 cases for mortality. Based on annual volumes, only 22% of hospitals met the minimum volume thresholds for a composite overall morbidity. In order to use other outcomes to assess quality, multiple year aggregate data are needed in order to generate volumes sufficient for comparison. Even with 5 year aggregate data less than 2% of hospitals could be compared based on mortality. CONCLUSIONS: For the vast majority of complications very few hospitals accrue enough procedure specific volume with appendectomy to judge quality even with multiple years of data collection. In order to best assess hospital quality in children's surgery alternate targets beyond procedure specific traditional outcomes warrant exploration. PMID- 24210206 TI - Characteristics of hospitals with lowest costs in management of pediatric appendicitis. AB - BACKGROUND: A primary determinant of value in treating appendicitis is inpatient cost. The purpose of this study was to identify hospital-level factors that drive costs associated with the treatment of appendicitis. METHODS: Cost-to-charge ratios from the 2009 Kids' Inpatient Database gave average all-payer costs by hospital for uncomplicated appendicitis (without peritonitis, ICD-9-CM 540.9) and complicated appendicitis (generalized peritonitis, 540.0; peritoneal abscess, 540.1). The 10% of hospitals with the lowest costs were defined as low cost; the remaining 90% were defined non-low cost. Bivariate and multivariate analyses compared hospital characteristics between the two groups. RESULTS: Threshold cost dividing low cost from non-low cost for uncomplicated appendicitis was $4626; for complicated appendicitis, it was $6,026. For both conditions teaching status, lower percentage of pediatric discharges, and fewer registered nurses (RN) per 1000 adjusted patient-days predicted a hospital to be low cost. A cost benefit for medium and large hospitals and higher inpatient volume was found only for uncomplicated appendicitis. Regional effects were noted. CONCLUSIONS: The findings show the high-cost structure of hospitals that care for high volumes of children, emphasizing the need to constrain cost. There is some benefit of economies of scale, and careful attention to the numbers of nursing personnel. PMID- 24210207 TI - A longitudinal cohort study of incidence rates of inguinal hernia repair in 0- to 6-year-old children. AB - BACKGROUND/PURPOSE: This study provides epidemiologic data on the incidence of inguinal hernia repair in preschool children using the Taiwan National Health Insurance Research Database. We believe that the data on hernia repair in said database provide a close approximation of the true incidence of inguinal hernia in young children. METHOD: A cohort of 1,073,891 deidentified individuals was randomly selected from an insured population of 23 million. Subjects born during the period 1997-2004 were followed from birth to 6 years. The chi-square test and logistic regression modeling were used for statistical analyses. RESULT: A total of 92,308 individuals were born during the study period. Of these individuals, 3881 underwent hernia repairs. The cumulative incidence of hernia repair in children aged 0 to 6 years was 4.20%/7 years. The boy/girl ratio was 4.27:1 and the unilateral/bilateral ratio was 3.77:1. The incidence of hernia repair among boys was highest during the first year of life, but then decreased with age. In contrast, the incidence among girls remained stable during the first 6 years of life. Boys younger than 1 year had more bilateral repairs than boys in other age groups (p<0.0001) and girls had significantly more bilateral repairs than boys (p<0.0001). Subjects with a history of preterm birth also had a higher incidence of hernia repair than subjects who were born at full term (odds ratio=2.34, p<0.0001). CONCLUSION: Yearly incidence of hernia repair was obtained from a nationwide database. Some of the observations have not been reported elsewhere. PMID- 24210208 TI - Using the parents' video camera for the follow-up of children who have undergone hypospadias surgery decreases hospital anxiety of children. AB - PURPOSE: We investigated the benefits of using the parents' video camera records for the follow-up of children who had undergone hypospadias surgery in terms of reducing fear and hospital anxiety of the children and the time spent in the waiting room. METHODS: This prospective study was performed on children with proximal hypospadias. The patients were called for the follow-up appointment on the 7th postoperative day and were divided into 3 groups. The first group was the control group where parents were not given any follow-up visit direction. The parents of the second group were told to have their child drink enough fluids and come with a full bladder, while the third group of parents recorded their child's micturition using a video camera. The fear and anxiety of children at the postoperative visit were evaluated and recorded using a scoring system between 0 and 4 using the Children's Fear Scale (CFS) brochure. The time elapsed from the arrival of the parents in the outpatient clinic to their departure was also recorded for comparison of the total time spent during the follow-up visit among the groups. RESULTS: Thirty boys who underwent hypospadias repair were enrolled in this study. The median CFS scores at the postoperative follow-up visit were 2.99+/-0.99 (range: 1-4) in the first group, 2.90+/-0.87 (range: 1-4) in the second group, and 0.00 (range 0-0) in the third group. The median total time spent during the follow-up visit in the 3 groups was 61.50+/-17.08 (range 35-88), 18.1+/-13.01 (range 4-45), and 4.0+/-0.81 (3-5) minutes, respectively. Both CFS and total time spent were significantly lower in the third group (p<0.01). CONCLUSION: Imaging of micturition at home by using a video camera for outpatient visits following hypospadias surgery will decrease the fear and anxiety of children and the time that the family spends at the hospital. PMID- 24210209 TI - Hepaticoduodenostomy versus hepaticojejunostomy after resection of choledochal cyst: a systematic review and meta-analysis. AB - BACKGROUND: Excision has been established as a standard management practice for choledochal cysts in the last few decades. The two most commonly performed methods of reconstruction after excision are hepaticoduodenostomy (HD) and Roux en-Y hepaticojejunostomy (HJ), of which the HJ is favored by most surgeons. Evidence concerning the optimal method of reconstruction is, however, sparse. MATERIALS AND METHODS: Studies comparing outcomes from HD and HJ after choledochal cyst excision were identified by searching Medline, Ovid, Search Medica, Elsevier Clinicalkey, Google Scholar and Cochrane library. Suitable studies were chosen and data extracted for meta-analysis. Outcomes evaluated included operative time, hospital stay and incidence of postoperative bile leak, cholangitis, reflux/gastritis, anastomotic stricture, bleeding, intestinal obstruction and re-operative rate. Pooled odds ratios (OR) were calculated for dichotomous variables; pooled mean differences (MD) were measured for continuous variables. RESULTS: Six retrospective studies were included in this meta analysis, comprising a total of 679 patients, 412 of whom (60.7%) underwent HD, and the remainder, 267 (39.3%) underwent HJ. Although, HD group had slightly shorter hospital stay (MD: 0.30; 95% CI: -0.22-0.39; P < 0.00001) it showed a higher incidence of postoperative reflux/gastritis (OR: 0.08; 95% CI: -0.02-0.39; P = 0.002). However, the other outcomes such as bile leak, cholangitis, anastomotic stricture, bleeding, operative time, reoperation rate and adhesive intestinal obstruction did not differ between HD and HJ groups. CONCLUSIONS: HD shows higher postoperative reflux/gastritis than HJ but a shorter hospital stay. There are few good-quality studies that compare the outcomes from HD and HJ, meaning that caution should be exercised in the generalization of the results of this meta-analysis, which suggests HD to be comparable with HJ in terms of other complications, operative benefits and outcomes. PMID- 24210210 TI - Long-term follow-up of functional outcome in patients with a cloacal malformation: a systematic review. AB - BACKGROUND: Reconstructive surgery is performed in patients with cloacal malformations to achieve anorectal, urological, and gynecological function. The aim of this study was to evaluate the functional outcome of cloacal malformation repair as reported in literature. METHODS: A systematic literature search was conducted according to PRISMA guidelines using PubMed, EMbase, and Web-of Science. Records were assessed for the reporting of functional outcomes, which was divided into anorectal, urological, or gynecological function. Studies were used in qualitative (Rangel score) and quantitative syntheses. RESULTS: Twelve publications were eligible for inclusion. Voluntary bowel movements were reported in 108 of 188 (57%), soiling in 146 of 205 (71%), and constipation in 31 of 61 patients (51%). Spontaneous voiding was reported for 138 of 299 patients (46%). 141 of 332 patients (42%) used intermittent catheterization, and 53 of 237 patients (22%) had a urinary diversion. Normal menstruations were reported for 25 of 71 patients (35%). Centers with limited experience reported similar outcome compared to centers with more experience (>=1 patients/year). CONCLUSION: In this review we present functional outcome of the largest pooled cohort of patients with cloacal malformations as reported from 1993 to 2012. Functional disturbances are frequently encountered in anorectal, urological, as well as gynecological systems. Reporting of functional outcome in these patients should improve to increase knowledge about long-term results in patients with this rare malformation and to reach higher study quality. Especially, sacral and spinal anomalies should always be reported given their impact on functional outcome. Specialized care centers may be of great importance for patients with rare and complex conditions. PMID- 24210211 TI - Modified Scharli technique for the very long gap esophageal atresia. AB - This modification of the Scharli technique which creates an isoperistaltic tube to overcome very long gap esophageal atresia involves retention of the short distal esophageal segment and creation of a neo-esophagus of tubularized gastric fundus of even calibre, similar to that of the upper esophageal segment. It has proved simple and effective in establishing esophageal continuity. PMID- 24210212 TI - [Reply to the letter on the article "PENTAX-AWS video laryngoscope, an alternative to intubation with fibrobronchoscopy in the awake patient with known difficult airway"]. PMID- 24210213 TI - [Ultrasound-guided peripheral nerve block at wrist level for the treatment of idiopathic palmar hyperhidrosis with botulinum toxin]. AB - OBJECTIVE: Evaluation of pain and degree of satisfaction in patients undergoing ultrasound-assisted peripheral regional block for the treatment of idiopathic palmar hyperhidrosis with botulinum toxin. PATIENTS AND METHODS: A descriptive, observational study of patients with palmar hyperhidrosis treated with botulinum toxin A, who underwent ultrasound-guided peripheral regional block of the median and ulnar nerves with 3 ml of mepivacaine 1% in each one. The radial nerve block was injected in the anatomical snuffbox. After establishing blocking, the dermatologist performed a mapping and injected around 100 IU of botulinum toxin across the whole palm. The pain experienced during the injection of botulinum toxin was evaluated by verbal numerical scale (from 0 to 10), along with the degree of satisfaction with the anesthetic technique, and the post-anesthetic complications. RESULTS: A total of 40 patients were enrolled in the study, 11 men and 29 women with no significant differences. The pain intensity assessed with verbal numerical scale was 1.03 (standard deviation of 1.37). No patients had a value greater than 5. The degree of patient satisfaction with the anesthetic technique was very good for 85% of the patients, and good for 7.5%. There were no complications related to type of anesthesia. CONCLUSIONS: The ultrasound-assisted peripheral regional block could be a simple, effective and safe technique for patients undergoing palmar injection of botulinum toxin. Pain intensity was very low, and it provided a very good level of satisfaction in most patients. PMID- 24210214 TI - [Comments to article "Video laryngoscope Pentax-AWS, an alternative to intubation with fiber bronchoscope in awake patient with foreseen difficult airway"]. PMID- 24210215 TI - [Reply to 'Intervention of clinical management units of physical medicine and rehabilitation in cerebrovascular disease']. PMID- 24210216 TI - [Intervention by physical medicine and rehabilitation management units in cases of cerebrovascular disease]. PMID- 24210217 TI - Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma. AB - CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients. PMID- 24210218 TI - Autophosphorylation activity of a soluble hexameric histidine kinase correlates with the shift in protein conformational equilibrium. AB - In a commonly accepted model, in response to stimuli, bacterial histidine kinases undergo a conformational transition between an active and inactive form. Structural information on histidine kinases is limited. By using ion mobility mass spectrometry (IM-MS), we demonstrate an exchange between two conformational populations of histidine kinase ExsG that are linked to different levels of kinase activity. ExsG is an atypical signaling protein that incorporates an uncommon histidine kinase catalytic core at the C terminus preceded by an N terminal "receiver domain" that is normally associated with the response regulator proteins in two-component signal transduction systems. IM-MS analysis and enzymatic assays indicate that phosphorylation of the ExsG receiver domain stabilizes the "compact" form of the protein and inhibits kinase core activity; in contrast, nucleotide binding required for kinase activity is associated with the more open conformation of ExsG. PMID- 24210219 TI - Biochemical and structural studies of conserved Maf proteins revealed nucleotide pyrophosphatases with a preference for modified nucleotides. AB - Maf (for multicopy associated filamentation) proteins represent a large family of conserved proteins implicated in cell division arrest but whose biochemical activity remains unknown. Here, we show that the prokaryotic and eukaryotic Maf proteins exhibit nucleotide pyrophosphatase activity against 5-methyl-UTP, pseudo UTP, 5-methyl-CTP, and 7-methyl-GTP, which represent the most abundant modified bases in all organisms, as well as against canonical nucleotides dTTP, UTP, and CTP. Overexpression of the Maf protein YhdE in E. coli cells increased intracellular levels of dTMP and UMP, confirming that dTTP and UTP are the in vivo substrates of this protein. Crystal structures and site-directed mutagenesis of Maf proteins revealed the determinants of their activity and substrate specificity. Thus, pyrophosphatase activity of Maf proteins toward canonical and modified nucleotides might provide the molecular mechanism for a dual role of these proteins in cell division arrest and house cleaning. PMID- 24210221 TI - Non-invasive monitoring during cardiac arrest: NIRS has potential but data remain limited. PMID- 24210220 TI - Design, synthesis, and biological evaluation of an allosteric inhibitor of HSET that targets cancer cells with supernumerary centrosomes. AB - Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics. PMID- 24210222 TI - Historical changes in trace metals and hydrocarbons in nearshore sediments, Alaskan Beaufort Sea, prior and subsequent to petroleum-related industrial development: part II. Hydrocarbons. AB - Composition and concentration of hydrocarbons (normal and isoprenoid alkanes, triterpenoids, steranes, and PAHs) in nearshore surface sediments from Elson Lagoon (EL), Colville Delta-Prudhoe Bay (CDPB) and Beaufort Lagoon (BL), Alaskan Beaufort Sea, were assessed for spatio-temporal variability. Principal component analysis of the molecules/biomarkers concentrations delineated CDPB and BL samples into two groups, and cluster analysis identified three station groups in CDPB. Overall there was no geographic distribution pattern in the groups. The diversities between groups and individual samples are attributed to differences in n-alkanes and PAHs contents, which are influenced predominantly by sediment granulometry and sitespecific fluvial input. The predominant hydrocarbon source is biogenic, mainly terrigenous, with hardly any contribution from natural oil seeps, oil drill effluents and/or refined crude. The terrigenous source is corroborated by delta(13)C, delta(15)N, and OC/N of sediment organic matter. Time interval (1976-1977, 1984 and 1997) changes in hydrocarbon compositions and concentrations in CDPB are not significant. PMID- 24210223 TI - Spatial budgetary evaluation of organochlorine contaminants in the sediments of Cochin Estuary, India. AB - This paper presents the first detailed investigation on the residual levels of organochlorine insecticide (OCI) concentrations in the Cochin estuarine sediment. It aims in elucidate their distribution and ecological impact on the aquatic system. Concentrations of persistent organochlorine compound (OC) were determined for 17 surface sediment samples which were collected from specific sites of Cochin Estuarine System (CES) over a period of November 2009 and November 2011. The contaminant levels in the CES were compared with other worldwide ecosystems. The sites bearing high concentration of organochlorine compounds are well associated with the complexities and low energy environment. Evaluation of ecotoxicological factors suggests that adverse biological effects are expected in certain areas of CES. PMID- 24210224 TI - Falling down: landscape and kinetics of one-dimensional protein folding. AB - In this issue of Structure, Tsytlonok and colleagues describe the folding landscape of the giant HEAT-repeat protein PR65/A (a molecular adaptor of protein phosphatase 2A) by using experimental and theoretical methods. Both approaches agree in suggesting the presence of parallel folding pathways with several intermediates. PMID- 24210225 TI - Surmounting an impasse of FcRn structure. AB - FcRn, resembling a major histocompatibility complex class I molecule with a closed peptide cleft, is an intracellular molecule that binds endocytosed albumin and IgG by a pH-dependent mechanism, diverting them from degradative fates and moving them out of the cell. The turnover of both of these important plasma proteins is thus regulated, as discussed by Schmidt and colleagues in this issue of Structure. PMID- 24210226 TI - A different look for AB5 toxins. AB - Metzincins are a distinct clan of metallopeptidases encompassing several families. In this issue of Structure, Ng and colleagues describe the results of the structural analysis of the toxilysins, a novel family of metzincins employed by gastroinfective bacteria as intracellular virulence factors following host cell invasion. PMID- 24210227 TI - Myosin structure, allostery, and mechano-chemistry. AB - Aberrant actomyosin interactions contribute to a wide range of pathophysiological conditions including heart failure, neurodegenerative disorders, and tumor growth. Despite surgical, interventional, and pharmacological advances, the burden and economic impact of these diseases remains immense. The initiation and progression of these disorders is frequently found to be a direct consequence of aberrant motile activity, which makes the in-depth investigation of the molecular mechanisms underlying actomyosin-dependent motility a prerequisite for the development of innovative treatment strategies. The present review describes key structural features of the actomyosin system, the basis of chemo-mechanical and allosteric coupling in the myosin motor domain, and molecular engineering and small molecule-based approaches to alter myosin function. PMID- 24210228 TI - Is diabetes mellitus a negative prognostic factor for the treatment of advanced non-small-cell lung cancer? AB - BACKGROUND: It has been demonstrated that there are a lot of different prognostic factors which are worthy of consideration whereas diabetes mellitus (DM) has not been clearly or consistently identified as a prognostic value in advanced non small cell lung cancer (NSCLC). The aim of this study was to investigate the prognostic significance of the characteristics of patients in advanced NSCLC. Specifically, we investigated the impact of DM for progression-free survival (PFS) and overall survival (OS) in patients receiving first-line platinum-based doublets chemotherapy. METHODS: We retrospectively reviewed 442 patients with advanced NSCLC. DM and other potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: The results of univariate analysis for OS were identified as having prognostic significance: performance status (p<0.001), stage (p<0.001), DM (p<0.001), liver metastasis (p=0.02) and brain metastasis (p<0.001). Stage, diabetes mellitus, and liver metastasis were identified as having prognostic significance for PFS. Multivariate analysis showed that poor performance status, presence of DM and advanced stage were considered independent negative prognostic factors for OS (p 0.001, p<0.001 and p<0.001 respectively). Furthermore, DM and stage were considered independent negative prognostic factors for PFS (p 0.005 and p 0.001 respectively). CONCLUSION: In conclusion, DM at the time of diagnosis was associated with the negative prognostic importance for PFS and OS in the advanced stage patients who were receiving first-line platinum-based doublets chemotherapy. In addition poor performance status and advanced stage were identified as negative prognostic factors. PMID- 24210229 TI - Elevated expression levels of matrix metalloproteinase-9 in placental villi and tissue inhibitor of metalloproteinase-2 in decidua are associated with prolonged bleeding after mifepristone-misoprostol medical abortion. AB - OBJECTIVE: To determine whether the expression levels of matrix metalloproteinases 2 and 9 (MMP-2 and -9) and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the villi and the decidua are associated with prolonged bleeding after medical abortion. DESIGN: Case controlled study. SETTING: University hospital. PATIENT(S): Mifepristone misoprostol medical abortion patients were divided into two groups (20 women each) based on the length of time (>14 or <=14 days) of bleeding after the abortion. INTERVENTION(S): Discharged villi and deciduas were collected. MAIN OUTCOME MEASURE(S): The expression levels of MMP-2 and -9 and TIMP-1 and -2 in the villi and deciduas were assessed with semiquantitative immunohistochemistry. RESULT(S): The median semiquantitative immunohistochemistry staining index (SI) scores for MMP-9 expression in the villi were elevated in the bleeding group compared with the control group (median SI scores 0.31 and 0.03, respectively). TIMP-2 expression was elevated in the decidua in the bleeding group compared with the control group (median SI scores 1.00 and 0.20, respectively). No significant differences were observed between the two groups in the expression levels of MMP 2 in the villi or of MMP-2, MMP-9, or TIMP-1 or of the ratios of MMP-9/TIMP-1 or MMP-2/TIMP-2 in the decidua. CONCLUSION(S): Elevated expression levels of MMP-9 in the villi and of TIMP-2 in the decidua were associated with prolonged bleeding after medical abortion. PMID- 24210230 TI - Influence of vitamin D levels on in vitro fertilization outcomes in donor recipient cycles. AB - OBJECTIVE: To elucidate the role of vitamin D in reproduction by examining the relationship between recipient vitamin D levels and pregnancy rates in donor recipient IVF cycles. DESIGN: Retrospective cohort study. SETTING: Academic tertiary care center. PATIENT(S): Ninety-nine recipients of egg donation at University of Southern California Fertility. INTERVENTION(S): Serum was collected from egg donor recipients before ET and was tested for vitamin D levels [25(OH)D]. MAIN OUTCOME MEASURE(S): Clinical pregnancy as defined by sonographic presence of a heartbeat at 7-8 weeks of gestation. RESULT(S): In a diverse population of 99 recipients (53% Caucasian, 20% Asian, 16% Hispanic, 7% African American), adjusted clinical pregnancy rates were lower among vitamin D-deficient recipients than among vitamin D-replete recipients (37% vs. 78%). Live-birth rates were 31% among vitamin D-deficient recipients, compared with 59% among vitamin D-replete recipients. There were no differences in adjusted clinical pregnancy and live-birth rates among recipients who were vitamin D deficient [25(OH)D<20 ng/mL] vs. among those who were vitamin D insufficient [20 ng/mL <= 25(OH)D<30 ng/mL]. CONCLUSION(S): Nonreplete vitamin D status [25(OH)D<30 ng/mL] was associated with lower pregnancy rates in recipients of egg donation. Since the oocyte donor-recipient model is able to separate the impact of vitamin D on oocyte vs. endometrium, these data suggest that the effects of vitamin D may be mediated through the endometrium. PMID- 24210231 TI - [Surgical treatments of presumed benign ovarian tumors]. AB - The surgical management of presumed benign ovarian tumors (PBOT) must ensure complete removal of the cyst, reduce the risk of recurrence (especially in case of endometrioma), prevent any risk of tumor dissemination, and must preserve healthy ovarian tissue. Asymptomatic PBOT should not be punctured. Expectation is preferable to puncture. Laparoscopy is the gold standard for surgical treatment. Single-port laparoscopy is feasible and being evaluated. Peritoneal exploration and peritoneal cytology are conventionally performed. Ovarian cystectomy, oophorectomy and salpingo-oophorectomy are the standard techniques. Suture after cystectomy is not recommended. The extraction of the cyst using an endoscopic bag is recommended. Peritoneal washing after surgery is recommended. The use of anti adhesions barriers is not recommended routinely. In case of dermoid cyst, cystectomy by mesial incision may decrease the risk of intraoperative rupture. In case of endometrioma, the intraperitoneal cystectomy is recommended as first-line surgery. Exclusive bipolar coagulation should be avoided because of increased risk of recurrence and lower pregnancy rates. There is no argument to support the use of plasma energy and CO2 laser in the treatment of endometriomas. Ethanol sclerotherapy may be proposed in patients with recurrent endometriomas after surgery and referred to medically assisted procreation, although there is no comparative trial with cystectomy. PMID- 24210232 TI - [Clinical practice guidelines: Presumed benign ovarian tumors--aims, methods, and organization]. PMID- 24210233 TI - [Presumed ovarian benign tumors and fertility]. AB - We reviewed the studies about fertility-sparing in young patient presenting a benign ovarian tumor. It appears that more than the histologic nature of the ovarian cysts, it is the surgical treatment of the cyst which may decrease fertility. Some good practice of surgical procedures must be kept in mind when one manages a benign ovarian tumor in a young patient wishing to preserve her fertility: surgery should be avoided as much as possible; kystectomy is better than oophorectomy; no radical surgery should be done without pathological certitudes; electrocoagulation must be avoided on the cyst walls. In some situations, fertility is specially endangered: bilateral ovarian cysts, recurrence or strong probability of recurrence (endometriomas), poor ovarian reserve (previous chemo- or radiotherapy, age>35, premature ovarian failure). In these situations, a pre-operative assessment of the ovarian reserve could be useful. Beside the surgical 'good procedures', gamete cryopreservation procedures could be used. Cryopreservation of mature oocytes (after ovarian hyperstimulation) or in vitro mature oocytes (after antral follicle retrieval) can be proposed. Ovarian tissue cryopreservation is another option. Oocyte (or embryos) cryopreservation can be proposed before or after the surgery. The global management of benign ovarian tumors in young patients should be decided between surgeons and specialists in reproductive biology. PMID- 24210234 TI - [Prevention of the complications related to hysteroscopy: guidelines for clinical practice]. AB - OBJECTIVE: To provide clinical practice guidelines (CPGs) from the French college of obstetrics and gynecology (CNGOF), based on the best evidence available, concerning the adverse events related to hysteroscopy. MATERIALS AND METHODS: Review of literature using following Keywords: hysteroscopy; vaginoscopy; infection; perforation; intrauterine adhesions RESULTS: Vaginoscopy should be the standard technique for outpatient hysteroscopy (grade A) using a miniature (<= 3.5mm sheath) (grade A) rigid hysteroscope (grade C), using normal saline solution distension medium (grade C), without any anesthesia (conscious sedation should not be routinely used), without cervical preparation (grade B), without vaginal disinfection and without antibiotic prophylaxy (grade B). Misoprostol (grade A), vaginal estrogens (grade C), or GnRH agonist routine administration is not recommended before operative hysteroscopy. Before performing hysteroscopy, it is important to purge the air out of the system (grade A). The uterine cavity distention pressure should be maintained below the mean arterial pressure and below 120 mmHg. The maximum fluid deficit of 2000 mL is suggested when using normal saline solution and 1000 mL is suggested when using hypotonic solution. When uterine perforation is recognized during operative hysteroscopy using monopolar or bipolar loop, the procedure should be stopped and a laparoscopy should be performed in order to eliminate a bowel injury. Diagnostic or operative hysteroscopy is allowed when an endometrial cancer is suspected (grade B). CONCLUSION: Implementation of this guideline should decrease the prevalence of complications related to office and operative hysteroscopy. PMID- 24210235 TI - [Epidemiology of presumed benign ovarian tumors]. AB - Ovarian cysts presumed benign can be organic or functional. Their prevalence is estimated between 14 and 18% in postmenopausal women and around 7% in asymptomatic women of childbearing age. Their incidence during pregnancy is between 0.2 and 5% and varies within the term of pregnancy. Ovarian cysts presumed benign have caused nearly 45,000 hospitalizations in France in 2012, bringing the annual risk of hospitalization for a woman residing in France to 1.30/00. Among the risk factors studied in the literature, tamoxifen increases the incidence of ovarian cysts in premenopausal patients and immunosuppressive treatments are associated with a high prevalence of benign ovarian cysts while estrogen contraception reduces the risk of developing functional cysts. PMID- 24210236 TI - [MRI and CT-scan in presumed benign ovarian tumors]. AB - Radiological examinations are required for the assessment of complex or indeterminate ovarian masses, mainly using MRI and CT-scan. MRI provides better tissue characterization than Doppler ultrasound or CT-scan (LE2). Pelvic MRI is recommended in case of an indeterminate or complex ovarian ultrasonographic mass (grade B). The protocol of a pelvic MRI should include morphological T1 and T2 sequences (grade B). In case of solid portion, perfusion and diffusion sequences are recommended (grade C). In case of doubt about the diagnosis of ovarian origin, pelvic MRI is preferred over the CT-scan (grade C). MRI is the technique of choice for the difference between functional and organic ovarian lesion diagnosis (grade C). It can be useful in case of clinical diagnostic uncertainty between polycystic ovary syndrome and ovarian hyperstimulation and multilocular ovarian tumor syndrome (grade C). No MRI classification for ovarian masses is currently validated. The establishment of a presumption of risk of malignancy is required in a MRI report of adnexal mass with if possible a guidance on the histological diagnosis. In the absence of clinical or sonographic diagnosis, pelvic CT-scan is recommended in the context of acute painful pelvic mass in non pregnant patients (grade C). It specifies the anomalies and allows the differential diagnosis with digestive and urinary diseases (LE4). Given the lack of data in the literature, the precautionary principle must be applied to the realization of a pelvic MRI in a pregnant patient. A risk-benefit balance should be evaluated case by case by the clinician and the radiologist and information should be given to the patient. In an emergency situation during pregnancy, pelvic MRI is an alternative to CT-scan for the exploration of acute pelvic pain in case of uncertain sonographic diagnosis (grade C). PMID- 24210237 TI - [Methods used to provide guidelines for clinical practice concerning the prevention of the complications related to hysteroscopy]. PMID- 24210238 TI - [Presumed benign ovarian tumors of childhood and adolescent]. AB - Ovarian tumors in childhood are rare, often organic with 10% of malignant cases. Functional pathology dominates in adolescence and its management is the same as the adult. The clinical symptoms of PBOT (presumed benign ovarian tumor) are non specific. The main clinical signs are acute pain, associated with peritoneal irritation syndrome, which can suggest an ovarian torsion, a mass or the development of secondary sexual characters. Hyperestrogenemia suggests a McCune Albright syndrome or a granulosa tumor. Hyperandrogenism evokes a malignant tumor. Pelvic ultrasound is the main examination. Pure liquid cysts are benign but could be organic if persisting beyond 6 months. MRI and tumor markers are needed for heterogeneous cyst diagnosis. The protected extraction of a cyst is recommended during the laparoscopic cystectomy. If case of doubt of malignancy, laparoscopy allows the peritoneal cavity exploration. In case of torsion, ovarian untwisting must be performed. After untwisting, the ovary must be preserved because macroscopic aspect is not predictive of the ovarian function recovery. No medical treatment is effective. After resection, US follow up is required for five years. PMID- 24210239 TI - [Diagnosis of presumed benign ovarian tumors]. AB - Symptoms of presumed benign ovarian tumors (PBOT) are not specific (LE4). Personal or family history of gynecological cancers can guide the diagnostic strategy. Clinical examination is ineffective for positive, topographic and etiologic diagnosis of PBOT (LE4). Signs of hormonal impregnation may refer to certain types of tumors (LE4). For any patient presenting with a pelvic mass, pelvic ultrasound is in the first-line exam (grade A); it can classify most ovarian tumors. In case of pure liquid unilocular mass smaller than 7 cm, ultrasound is sufficient to characterize the mass (grade A). In case of indeterminate or complex ovarian mass on ultrasound, MRI is useful to characterize the mass (LE2). Beyond 7 cm, the diagnostic performance of ultrasound decreases (LE2). When a non-unilocular liquid ovarian formation is characterized using ultrasound as determinate mass, ultrasound scan is the only exam recommended (grade B). MRI is indicated as a second-line scan for indeterminate masses or greater than 7 cm (grade B). Cyst puncture for diagnostic purposes has no place in the diagnostic strategy of ovarian cysts (grade C). In case of PBOT in pre-pubertal period, dosing biomarkers is useful but should not delay care. In adult women with PBOT, the measurement of CA125 is not recommended for first-line diagnosis (grade C). Current literature data are not sufficient to specify the diagnostic strategy for an ovarian tumor discovered incidentally during laparoscopy. In case of discovery of a high CA125 value, pelvic ultrasound is the first-line examination. The literature data are still limited to define a CA125 threshold value requiring further exploration or special monitoring, in case of normal pelvic ultrasound. PMID- 24210240 TI - [Complications of presumed benign ovarian tumors]. AB - The main risk factor of adnexal torsion is a previous adnexal torsion (LE3). There is no clinical, biological or radiological sign that may exclude the diagnosis of adnexal torsion (LE3). The presence of flow at color Doppler imaging does not allow exclusion of the diagnosis (LE2). An emergent laparoscopy is recommended for adnexal untwisting (Grade B), except in postmenopausal women where oophorectomy is recommended (grade C). A persistent black color of the adnexa after untwisting is not an indication for systematic oophorectomy (grade C), since a functional recovery is possible (LE3). Ovariopexy is not routinely recommended following adnexal untwisting (grade C). The clinical signs of intra cystic hemorrhage and those of rupture of the corpus luteum are not specific (LE4). MRI is not recommended to confirm the diagnosis of intra-cystic hemorrhage (grade C). Malignant transformation of an ovarian cyst is very rare. The presence of a benign ovarian cyst is not associated with an increased risk of ovarian cancer at long-term follow-up (LE2). For these women, an ultrasound follow-up is not recommended (grade C). Dermoid ovarian cyst containing nerve tissue can trigger the production of pathogenic auto-antibody-anti-NMDA, leading to encephalitis. A high proportion of thyroid tissue in a mature teratoma (struma ovarii) may cause hyperthyroidism. PMID- 24210241 TI - [Medical treatments of presumed benign ovarian tumors]. AB - Medical treatment of functional cysts and endometriomas, and the risk of developing functional ovarian cysts in different therapeutic situations are assessed. The available literature regarding the treatment of functional cysts is limited both by the number of studies and the variability of criteria used to define cysts. There is no evidence to support any efficiency of a medical treatment (LE1). However, oral contraceptive use reduces the risk of development of functional cysts (LE2). Using a second generation combination is recommended as a first-line option in order to reduce thromboembolic risk (LE1). Tamoxifen is significantly associated with an increased risk of developing unilocular cysts before menopause (LE2). For endometriomas, GnRH-agonists are not recommended before cystectomy in order to facilitate surgery (grade C) or to prevent recurrence (grade B). After surgery of endometriomas, the use of an intrauterine device with levonorgestrel or oral contraceptives significantly reduces the volume of the cyst in case of recurrence (LE3); oral contraceptives reduce the recurrence rate of endometriomas (LE2); the use of a low-dose oral contraceptive decreases the frequency and severity of long-term dysmenorrhea (LE1). PMID- 24210242 TI - [Presumed benign ovarian tumors during pregnancy]. AB - The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4). PMID- 24210243 TI - [Ovarian tumor markers of presumed benign ovarian tumors]. AB - Cancer Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are the most studied ovarian tumor markers. Their diagnostic performance for identification of ovarian cancer are superior to CA19-9, CA72-4, and carcinoembryonic antigen, which are no more recommended for the diagnosis of presumed benign ovarian tumor. HE4 (>140 pmol/L) is superior to CA125 (>30 U/mL) in terms of specificity and positive likelihood ratio. CA125 and HE4 can be combined into an algorithm ROMA, or associated to clinical information (composite index), biological data (OVA1) or imaging (Risk for Malignancy Index (RMI), LR2). ROMA algorithm is an exponential equation combining plasmatic concentrations of HE4 and CA125. ROMA is more sensitive and less specific than HE4 in predicting epithelial ovarian cancer. ROMA is more accurate in post-menopausal women. The performance of ROMA is lower than the ultrasound model LR2 in differentiating malignant from benign ovarian tumors, whatever the hormonal status. The composite index combining CA125 with a symptoms index (pain, abdominal distension, bloating, difficulty eating) has a good sensitivity in a screening program, but because of a 12% false positive rate, ultrasound is required before management. The RMI algorithm is based on serum CA125, ultrasound findings (septation, solid zones, metastases, ascite, bilaterality) and menopausal status. RMI is less sensitive, but more specific than ROMA or OVA1 for the classification of ovarian masses. The addition of HE4 to RMI seems to be the most accurate. The subjective evaluation of ovarian cysts by sonography and color Doppler is better than ROMA and RMI algorithms, and not affected by the hormonal status. PMID- 24210244 TI - Dermatobia hominis (Diptera: Cuterebridae) in Africa and the need for caution in its taxonomy. PMID- 24210245 TI - Factors associated with dengue fever IgG sero-prevalence in South Kordofan State, Sudan, in 2012: Reporting prevalence ratios. AB - BACKGROUND: Dengue fever (DF) is a vector-borne virus transmitted to humans by infected Aedes mosquitoes. In this study, we identified the most important factors associated with the prevalence of IgG antibodies in a border state between Sudan and the new republic of South Sudan. OBJECTIVES: To quantify the association of specific factors with the prevalence of DF IgG antibodies in Lagawa among subjects aged 16-60 years in 2012. METHODOLOGY: Analytical cross sectional community-based study conducted in Lagawa in 2012. RESULTS: Indoor mosquito breeding was the most significant predictor affecting DF IgG serology. Household water storage was also strongly associated with the presence of IgG antibodies. Residence in urban areas, younger age and a history of travel to the Red Sea State were significant predictors of DF IgG seroprevalence in South Kordofan state. CONCLUSION: Indoor (household) behaviors associated with DF infection should be modified to mitigate the infection risk in the study area. Awareness should be raised regarding DF in Lagawa to ensure community participation in all control measures, and the surveillance system at the border between Sudan and the republic of South Sudan should be strengthened. PMID- 24210246 TI - Evaluation of the potential impact of a carbapenem de-escalation program in an academic healthcare system. AB - The primary objective of this analysis was to evaluate group 2 carbapenem usage and to model the impact that a formalized de-escalation protocol to ertapenem could potentially have on group 2 carbapenem usage in the hope of alleviating the selective pressure on Acinetobacter and Pseudomonas. This analysis was conducted in three hospitals within the Detroit Medical Center in 2009. Patients were considered candidates for de-escalation of carbapenem therapy when a group 2 carbapenem was utilized to treat Enterobacteriaceae, such as extended spectrum beta-lactamase (ESBL)-producing organisms, or if cultures were negative in non intensive care unit (ICU) patients. In total, 179 patients (28%) and 1074 patient days (29%) were deemed eligible for de-escalation according to our pre-defined criteria. We concluded that preferential utilization of ertapenem in appropriate patients warranting carbapenem therapy has the potential to significantly decrease group 2 carbapenem usage at our institution. PMID- 24210247 TI - Catalytic degradation of organic dyes using biosynthesized silver nanoparticles. AB - The green synthesis of metallic nanoparticles paved the way to improve and protect the environment by decreasing the use of toxic chemicals and eliminating biological risks in biomedical applications. Plant mediated synthesis of metal nanoparticles is gaining more importance owing to its simplicity, rapid rate of synthesis of nanoparticles and eco-friendliness. The present article reports an environmentally benign and unexploited method for the synthesis of silver nanocatalysts using Trigonella foenum-graecum seeds, which is a potential source of phytochemicals. The UV-visible absorption spectra of the silver samples exhibited distinct band centered around 400-440 nm. The major phytochemicals present in the seed extract responsible for the formation of silver nanocatalysts are identified using FTIR spectroscopy. The report emphasizes the effect of the size of silver nanoparticles on the degradation rate of hazardous dyes, methyl orange, methylene blue and eosin Y by NaBH4. The efficiency of silver nanoparticles as a promising candidate for the catalysis of organic dyes by NaBH4 through the electron transfer process is established in the present study. PMID- 24210248 TI - Micromorphology of cactus-pear (Opuntia ficus-indica (L.) Mill) cladodes based on scanning microscopies. AB - Cladode ultrastructural features of two prickly and two spineless Opuntia ficus indica cultivars were examined using environmental scanning electron and atomic force microscopies. Observations focused on cladode as well as spine and glochid surface micromorphologies. Prickly cultivars were characterized by abundant cracked epicuticular wax deposits covering the cladode surface, with an amorphous structure as observed by AFM, while less abundant waxy plates were observed by ESEM on spineless cultivar cladodes. Further AFM observations allowed a rough granular and crystalloid epicuticular wax structure to be distinguished in spineless cultivars. Regarding spine micromorphology, prickly cultivars had strong persistent spines, observed by ESEM as a compact arrangement of oblong epidermal cells with a rough granular structure. However, deciduous spines in spineless cultivars had a broken transversely fissured epidermis covering a parallel arrangement of fibres. Through AFM, the deciduous spine surface presented an irregular hilly and smooth microrelief while persistent spines exhibited rough helical filamentous prints. ESEM and AFM studies of cladode surfaces from prickly and spineless cactus pear cultivars revealed valuable micro morphological details that ought to be extended to a large number of O. ficus indica cultivars. PMID- 24210249 TI - Evaluation of the respiratory elimination kinetics of selenate and Se methylselenocysteine after oral administration in lambs. AB - Sheep can be acutely poisoned by selenium (Se) accumulating forages which often contain selenate or Se-methylselenocysteine as their predominant forms. Excess Se can be eliminated via respiration. Sheep were given a single oral dose of 0, 1, 2, 3, 4, or 6 mg Se/kg BW as sodium selenate and Se-methylselenocysteine or 6 mg Se/kg BW as sodium selenite or selenomethionine. Expired air samples were collected and analyzed for Se. The Se concentration of the expired air reflected a dose-dependent increase at individual time points for both Se methylselenocysteine and sodium selenate, however, Se content was greater and eliminated more rapidly from sheep receiving Se-methylselenocysteine. The mean Se concentration in respired air from sheep administered 6 mg Se/kg BW of different selenocompounds was greatest in sheep dosed Se-methylselenocysteine > selenomethionine > sodium selenate > sodium selenite. The Se concentration in respired air of acutely poisoned sheep is significantly different for different chemical forms of Se. PMID- 24210250 TI - Early MRI in term infants with perinatal hypoxic-ischaemic brain injury: interobserver agreement and MRI predictors of outcome at 2 years. AB - AIM: To compare diffusion-weighted imaging (DWI) and non-DWI magnetic resonance imaging (MRI), proton MR spectroscopy (1H-MRS), and clinical biomarkers for prediction of 2 year developmental outcome in term infants with perinatal hypoxic ischaemic encephalopathy (HIE). MATERIALS AND METHODS: Nineteen infants >=36 weeks gestation with HIE were recruited and MRI performed day 3-7 (mean = 5). MRI was scored independently by three radiologists using a standardized scoring system. Lactate-to-N-acetylaspartate ratio (Lac:NAA) in the lentiform nucleus was calculated. Developmental assessment was performed at 2 years using the Bayley Scales of Infant and Toddler Development (BSID-III). Interobserver agreement about abnormality in 10 brain regions was measured. Univariate analysis was performed to determine variables associated with adverse outcome (i.e., death or Bayley score for any domain <70). RESULTS: Good interobserver agreement (kappa = 0.61-0.69) on scores for DWI was obtained for the cortex, putamen, and brainstem, but not for any region on non-DWI. A significant association was found between outcome and Lac:NAA (p < 0.003) and DWI scores for lentiform nucleus, thalamus, cortex, posterior limb of the internal capsule (PLIC), and paracentral white matter (p = 0.001-0.013), but for non-DWI score only in the vermis or brainstem. A combination of Lac:NAA >=0.25 or DWI/apparent diffusion coefficient (ADC) signal abnormality in the PLIC had 100% specificity and sensitivity for poor outcome. CONCLUSION: Interobserver agreement for non-DWI performed during the first week is poor. Agreement by three radiologists about the presence of abnormal signal within the PLIC on ADC/DWI images or elevation of Lac:NAA above 0.25 improved sensitivity without reducing the prognostic specificity of MRS in the 19 patients, but this requires validation in a larger group of infants with HIE who have been treated with hypothermia. PMID- 24210251 TI - Beyond GWASs: illuminating the dark road from association to function. AB - Genome-wide association studies (GWASs) have enabled the discovery of common genetic variation contributing to normal and pathological traits and clinical drug responses, but recognizing the precise targets of these associations is now the major challenge. Here, we review recent approaches to the functional follow up of GWAS loci, including fine mapping of GWAS signal(s), prioritization of putative functional SNPs by the integration of genetic epidemiological and bioinformatic methods, and in vitro and in vivo experimental verification of predicted molecular mechanisms for identifying the targeted genes. The majority of GWAS-identified variants fall in noncoding regions of the genome. Therefore, this review focuses on strategies for assessing likely mechanisms affected by noncoding variants; such mechanisms include transcriptional regulation, noncoding RNA function, and epigenetic regulation. These approaches have already accelerated progress from genetic studies to biological knowledge and might ultimately guide the development of prognostic, preventive, and therapeutic measures. PMID- 24210252 TI - Accurate local-ancestry inference in exome-sequenced admixed individuals via off target sequence reads. AB - Estimates of the ancestry of specific chromosomal regions in admixed individuals are useful for studies of human evolutionary history and for genetic association studies. Previously, this ancestry inference relied on high-quality genotypes from genome-wide association study (GWAS) arrays. These high-quality genotypes are not always available when samples are exome sequenced, and exome sequencing is the strategy of choice for many ongoing genetic studies. Here we show that off target reads generated during exome-sequencing experiments can be combined with on-target reads to accurately estimate the ancestry of each chromosomal segment in an admixed individual. To reconstruct local ancestry, our method SEQMIX models aligned bases directly instead of relying on hard genotype calls. We evaluate the accuracy of our method through simulations and analysis of samples sequenced by the 1000 Genomes Project and the NHLBI Grand Opportunity Exome Sequencing Project. In African Americans, we show that local-ancestry estimates derived by our method are very similar to those derived with Illumina's Omni 2.5M genotyping array and much improved in relation to estimates that use only exome genotypes and ignore off-target sequencing reads. Software implementing this method, SEQMIX, can be applied to analysis of human population history or used for genetic association studies in admixed individuals. PMID- 24210253 TI - Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease. AB - Nutritional intervention may retard the development of Alzheimer's disease (AD). In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model (APPswe/PS1dE9). One diet contained membrane precursors such as omega-3 fatty acids and uridine monophosphate (DEU), whereas another diet contained cofactors for membrane synthesis as well (Fortasyn); the diets were developed to enhance synaptic membranes synthesis, and contain components that may improve vascular health. We measured cerebral blood flow (CBF) and water diffusivity with ultra-high-field magnetic resonance imaging, as alterations in these parameters correlate with clinical symptoms of the disease. APPswe/PS1dE9 mice on control diet showed decreased CBF and changes in brain water diffusion, in accordance with findings of hypoperfusion, axonal disconnection and neuronal loss in patients with AD. Both multinutrient diets were able to increase cortical CBF in APPswe/PS1dE9 mice and Fortasyn reduced water diffusivity, particularly in the dentate gyrus and in cortical regions. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms. PMID- 24210254 TI - Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice. AB - Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. PMID- 24210255 TI - Commensal microbiota and NKT cells in the control of inflammatory diseases at mucosal surfaces. AB - Natural Killer T (NKT) cells are a phenotypically and functionally diverse subset of T cells, which recognizes self- and microbial lipids in the context of the atypical MHC class I molecule CD1d. NKT cells exhibit potent effector functions and play critical roles in antimicrobial defense, cancer immunosurveillance and the modulation of immune-mediated disorders. Recent evidence has revealed extensive cross-regulation between the mucosal microbiota and CD1d as well as NKT cells. Microbial exposure at mucosal surfaces, particularly during early postnatal development, regulates NKT cell trafficking and function in the intestine and the lung and determines the susceptibility to NKT cell-mediated inflammatory disorders. Conversely, CD1d controls the composition of the intestinal microbiota; perhaps through the regulation of Paneth cell function. Here, we provide an overview of recent findings on the crosstalk between the microbiota and NKT cells and discuss the implication for mucosal homeostasis and its dysregulation in inflammatory disorders. PMID- 24210256 TI - Stuck in a rut? Reconsidering the role of parasite sequestration in severe malaria syndromes. AB - Severe malaria defines individuals at increased risk of death from their infection. Proposed pathogenic mechanisms include parasite sequestration, inflammation, and endothelial dysfunction. Severe malaria is not a single entity, manifesting with distinct syndromes such as severe anemia, severe respiratory distress or coma, each characterized by differences in epidemiology, underlying biology, and risk of death. The relative contribution of the various pathogenic mechanisms may differ between syndromes, and this is supported by accumulating evidence, which challenges sequestration as the initiating event. Here we propose that high parasite biomass is the common initiating feature, but subtle variations in the interaction between the host and parasite exist, and understanding these differences may be crucial to improve outcomes in patients with severe malaria. PMID- 24210264 TI - [Pathophysiology of Behcet's disease]. AB - Although the precise pathogenesis and etiology of Behcet's disease (BD) still remains unknown, current evidence suggests that inflammatory reaction in BD arises from disruption of homeostasis in genetically susceptible individuals, resulting in altered innate and adaptive immunity responses, pathogenic T cell activation in the peripheral blood, and in inflammatory sites. Association with HLA-B51 is known as the strongest genetic susceptibility factor for BD. Recent GWAS (genome-wide association studies) have confirmed this relationship, and reported new susceptibility genes (IL-10, IL-23R, IL-12RB2) for the disease. A triggering infectious agent could operate through molecular mimicry, and the disease could subsequently be perpetuated by an abnormal immune response to an auto-antigen in the absence of ongoing infection. Several potential bacteria have been investigated but the most commonly implicated microorganism is Streptococcus sanguis. Recent data have showed that the T cell homeostasis perturbation consisted mainly of Th1 and Th17 expansions, while regulatory T cell response was suppressed. Cytokine such as IL-17, IL-23 and IL-21 play a significant role in the pathogenesis of BD. Inflammatory cells within BD inflammatory lesions include mostly neutrophils, CD4(+) T cells, and cytotoxic cells. Lastly, endothelium dysfunction has been clearly established. This improved understanding of the pathophysiology of BD will certainly lead to the development of new therapeutic agents, potentially more effective than current therapy. In this review, we have studied the etiopathogenesis of BD in the light of recent advances. PMID- 24210257 TI - Effects of air pollution on exhaled nitric oxide in children: results from the GINIplus and LISAplus studies. AB - Most previous studies which have investigated the short-term effects of air pollution on airway inflammation, assessed by an increase of exhaled nitric oxide (eNO), have been conducted among asthmatic children. Few studies have considered this potential association among non-asthmatics. Furthermore, although both short and long-term effects of air pollution on eNO had been reported separately, studies which include both are scarce. We explored associations between 24h NO2 and PM10 (particles with aerodynamic diameters below 10MUm) mass with eNO in 1985 children (192 asthmatics and 1793 non-asthmatics) aged 10 years and accounted for the long-term effects of air pollution by adjusting for annual averages of NO2, PM10 mass, PM2.5 mass (particles with aerodynamic diameters below 2.5MUm) and PM2.5 absorbance, using data from two German birth cohorts in Munich and Wesel. In total, robust associations between 24h NO2 and eNO were observed in both single-pollutant (percentage change: 18.30%, 95% confidence interval: 11.63 25.37) and two-pollutant models (14.62%, 6.71-23.11). The association between 24h PM10 mass and eNO was only significant in the single-pollutant model (9.59%, 4.80 14.61). The same significant associations were also observed in non-asthmatic children, while they did not reach significant levels in asthmatic children. Associations between annual averages of ambient air pollution (NO2, PM10 mass, PM2.5 mass and PM2.5 absorbance) and eNO were consistently null. In conclusion, significantly positive associations were observed between short-term ambient air pollution and eNO. No long-term effects of air pollution on eNO were found in this study. PMID- 24210265 TI - [Pediatric Behcet's disease]. AB - Behcet's disease is a chronic multisystem vasculitis of unknown etiology. The disease is commonly described in young adults but can occur in childhood. Diagnosis is based on clinical manifestations since there are no pathognomonic laboratory findings. Early diagnosis in children is challenging due to the insidious nature of the disease and the low sensitivity of adult criteria in the pediatric population. The purpose of this review is to describe the demographic and clinical features of Behcet's disease in childhood, its complications and recent advances in therapeutics highlighting differences with the adult onset disease. PMID- 24210266 TI - [Scleritis, clinical features, etiologies and treatment: a case series of 32 patients]. AB - PURPOSE: To report on the various clinical presentations, etiological diagnosis, prognosis and treatment of patients with scleritis evaluated at a tertiary care eye center. METHODS: Retrospective, monocentric study on a series of 32 patients in a tertiary center. RESULTS: The mean age of included patients with scleritis was 46.8 years (range, 22 to 77 years). Nineteen patients were women and 13 were men. Twenty-six patients (81%) had anterior scleritis (15 nodular, 8 diffuse and 3 necrotizing), six (19%) had posterior scleritis. Unilateral inflammation was present in 24 patients (75%). Twelve out of the 32 patients (37.5%) had an underlying systemic disease: granulomatosis with polyangiitis (n=3), Behcet's disease (n=2), unspecified inflammatory arthritis (n=2), psoriatic arthritis (n=1), ankylosing spondylitis (n=1), sarcoidosis (n=1), Cogan's syndrome (n=1) and ulcerative colitis (n=1). Six patients (18.8%) were suspected of having infectious disease with herpes virus: clinical context and positive treatment response with oral valacyclovir. Systemic agents and topical agents were required in 28 patients (87.5%). The first line therapy was mainly oral non-steroidal anti inflammatory drugs in 15 patients (47%) and oral corticosteroids in 8 (25%). Immunosuppressive drugs were required in 6 patients. The mean follow-up was 16.3 months. Six patients (19%) had a decrease in visual acuity. CONCLUSION: The number of systemic disease in our series is similar to the main series in the literature. Treatment with valaciclovir might be effective in patients with suspected herpes simplex scleritis. PMID- 24210267 TI - Anomalous ophthalmic artery arising from middle meningeal artery: potential risk of visual complication in frontotemporal craniotomy. PMID- 24210268 TI - Whole brain CT perfusion combined with CT angiography in patients with subarachnoid hemorrhage and cerebral vasospasm. AB - OBJECTIVE: To assess cerebral vasospasm (CVS) and monitor cerebral microcirculatory changes in patients with acute subarachnoid hemorrhage (SAH) via CT angiography (CTA) combined with whole-brain CT perfusion (CTP) techniques. METHODS: Sixty patients with SAH (SAH group) and 10 patients without SAH (control group) were selected for a prospective study. CTP combined with CTA and digital subtraction angiography (DSA) studies were performed on patients with initial onset of SAH less than three days. CTA and DSA as well as the CTP parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) were acquired and analyzed. The relationship of CTA and CTP measurements was assessed in these acute SAH patients. RESULTS: CTP techniques were used to achieve the perfusion maps of the whole brain in patients with acute SAH. Compared to the control group, mean CBF value was significantly lower while both MTT and TTP values were significantly higher in SAH group (all p<0.05). Further analysis revealed that mean CBF in patients with CVS, sCVS, Fisher III-IV and Hunt-Hess III-V significantly decreased when compared to patients with nCVS, asCVS, Fisher I-II and Hunt-Hess I-II (p<0.05). Furthermore both MTT and TTP values were also significantly reduced in patient with CVS, sCVS, Fisher III-IV and Hunt-Hess III-V (p<0.05). CONCLUSION: The study demonstrated that changes of microcirculation in patients with SAH could be assessed by whole-brain CTP. CTP combined with CTA could detect both macroscopic evident vasospasm on CTA and alterations of microcirculation on CTP. Mean CBF was significantly lower in patients with SAH. PMID- 24210269 TI - Safety and long-term efficacy of endovascular treatment of small posterior communicating artery aneurysms by coiling with or without stent: a single center retrospective study. AB - OBJECTIVES: Endovascular stents have been widely used in intracranial aneurysm embolization. In this work, we compared the safety and long-term efficacy of stent-assisted coiling with those of conventional coiling for small posterior communicating artery aneurysms, aiming at a better understanding of the related safety and efficacy profiles. METHODS: Between January 2008 and December 2011, 114 small PcomA aneurysms (defined as 3mm<=maximum diameter<10mm in this study) in 108 patients were treated by endovascular treatment in our department. Patient demographics, aneurysm characteristics, angiographic results (initial and follow up), and procedural complications were assessed. RESULTS: Embolization was successfully performed in all the patients. Complications occurred in 7.4% of patients in both groups. There was no associated mortality. Based on initial post procedural angiography, the rate of complete aneurysm occlusion, neck remnant and residual sac in the stented group were 37.9%, 24.1%, and 37.9%, while in the conventional group the figures were 42.9%, 48.2%, and 8.9%, respectively. The initial angiographic results were significantly better in the conventional group, compared with the stented group (P=0.038). The follow-up results showed that the rate of improvement in the stented group was significantly higher (53.3% vs. 14.0%; P<0.001) and the recurrence rate was significantly lower than that in the conventional group (4.4% vs. 3.02%; P=0.001). CONCLUSION: Compared with conventional coiling, stent-assisted coiling of the small posterior communicating artery aneurysms does not increase the risk. Stents bear an advantage in reducing the recurrence rate, increasing progressive occlusion rate, and improving long term prognosis in endovascular treatment of intracranial aneurysms. PMID- 24210270 TI - Childhood sexual experiences with an older partner among men who have sex with men in Buenos Aires, Argentina. AB - This study sought to describe childhood sexual experiences with older partners (CSEOP) among men who have sex with men (MSM) in Buenos Aires, Argentina. MSM were recruited through respondent driven sampling. They responded to a computer administered self-interview with questions on CSEOP, operationalized as manual, oral, genital, or anal contact prior to age 13 with a partner at least 4 years older. Of the 500 respondents, only 25% identified as gay. Eighteen percent of the respondents reported CSEOP, the majority of whom did not feel they were hurt by the experience and did not consider it to be childhood sexual abuse (CSA). Over two-thirds of MSM who reported CSEOP said that their older partner was a female. Only 4% of those with a female partner felt their experience was CSA compared to 44% of those who had a male partner. Among all men reporting CSEOP, those who felt sexually abused were more likely to have been physically forced or threatened, physically hurt, and emotionally hurt than those who did not feel sexually abused. Having CSEOP, being hurt by the experiences, and perceiving the experiences as sexual abuse were not associated with current HIV sexual risk or substance use behavior. In this sample of MSM in Argentina, a substantial minority reported CSEOP. Those who felt they had been sexually abused were much more likely to have had an older male partner than an older female partner, and were more likely to report having been physically forced and threatened by their older partner. PMID- 24210271 TI - Cumulative childhood trauma and psychological maladjustment of sexually abused children in Korea: mediating effects of emotion regulation. AB - The purpose of the present study was to identify the mediating effects of emotion regulation on the association between cumulative childhood trauma and behavior problems in sexually abused children in Korea, using structural equation modeling (SEM). Data were collected on 171 children (ages 6-13 years) referred to a public counseling center for sexual abuse in Seoul, Korea. Cumulative childhood traumas were defined on the basis of number of traumas (physical abuse, witnessing domestic violence, neglect, traumatic separation from parent, and sexual abuse) and the severity and duration of traumas. Children were evaluated by their parents on emotion regulation using the Emotion Regulation Checklist and internalizing and externalizing behavior problems using the Korean-Child Behavior Checklist. SEM analyses confirmed the complete mediation model, in which emotion dysregulation fully mediates the relationship between cumulative childhood traumas and internalizing/externalizing behavior problems. These findings indicate that emotion regulation is an important mechanism that can explain the negative effects of cumulative childhood traumas and that there is a need to focus on emotion regulation in sexually abused children exposed to cumulative trauma. PMID- 24210272 TI - Does a paradox exist in child well-being risks among foreign-born Latinos, U.S. born Latinos, and Whites? Findings from 50 California cities. AB - Past research has identified "paradoxes" in infant health and child welfare services involvement, whereby children of Latinos and immigrants often demonstrate better health and decreased risk for child protective services involvement when compared to whites of similar socioeconomic position. This population-based study examined whether a paradox exists among immigrant and U.S. born Latino caregivers in the prevalence and magnitude of risks to child well being when compared to whites of similar socioeconomic position. Data were drawn from a random, general population telephone survey of parenting practices in 50 California cities (n=2,259), which was administered in English and Spanish. The sample included 1,625 U.S.-born whites (72.0%), 351 U.S.-born Latinos (15.5%) and 283 foreign-born Latino respondents (12.5%). After adjusting for covariates in logistic regression models stratified by household income, immigrant caregivers in lower income households reported odds of insufficient food for the child that were 12 times as large as those for whites (OR 11.97, 95% CI 2.87, 49.86); odds of reported inability to take the child to the doctor and leaving a child in a place of questionable safety were nearly eight times as large (OR 7.92, 95% CI 2.38, 26.36 and OR 7.93, 95% CI 1.73, 36.46 respectively). These relationships were attenuated or insignificant for immigrant caregivers in households with greater resources. Therefore, a paradoxical relationship between socioeconomic position and risks to child well-being was not identified. Further research is needed to better understand the complex relationships between such risks, child health, and child protective services involvement. PMID- 24210273 TI - A finite volume method and experimental study of a stator of a piezoelectric traveling wave rotary ultrasonic motor. AB - Piezoelectric traveling wave rotary ultrasonic motors are motors that generate torque by using the friction force between a piezoelectric composite ring (or disk-shaped stator) and a metallic ring (or disk-shaped rotor) when a traveling wave is excited in the stator. The motor speed is proportional to the amplitude of the traveling wave and, in order to obtain large amplitudes, the stator is excited at frequencies close to its resonance frequency. This paper presents a non-empirical partial differential equations model for the stator, which is discretized using the finite volume method. The fundamental frequency of the discretized model is computed and compared to the experimentally-measured operating frequency of the stator of Shinsei USR60 piezoelectric motor. PMID- 24210275 TI - Bortezomib: a therapeutic resource for the veterinary oncologist? PMID- 24210274 TI - DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology. AB - Type 1 diabetes (T1D) shows ~40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional annotation of the genes with distinct CpG methylation profiles in T1D samples showed differential DNAm of immune response and defense response pathways between affected and unaffected twins. Integration of DNAm data with GWAS data mapped several known T1D associated genes, HLA, INS, IL-2RB, CD226, which showed significant differences in DNAm between affected and unaffected of twins. Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of T1D. PMID- 24210276 TI - Ketone bodies upregulate endothelial connexin 43 (Cx43) gap junctions. AB - Ketosis occurs as a metabolic consequence of negative energy balance in post calving lactating dairy cows. Metabolism of free fatty acids, released from adipose tissue, generates excessive amounts of acetoacetate (AcAc), beta hydroxybutyrate (BHB), and acetone (Ac) in the liver, which are released into the blood. The effects of ketone bodies on endothelial cells include increased rates of portal vein and liver blood flow and decreased cytokine secretion in response to both bacterial and viral infections. The aim of the current study was to understand the effects of AcAc, BHB and Ac, on expression of connexin 43 (Cx43) and gap junctional intercellular coupling (GJIC) in bovine aortic endothelial cells (BAECs). Confocal microscopy, Western blotting, and real-time quantitative RT-PCR indicated that Cx43 mRNA and protein expression increased after endothelial cell exposure to ketone bodies and that this was accompanied by upregulation of GJIC and cell migration. These effects were most obvious when BAECs were treated with a combination of the three ketones. Ketone bodies were shown to activate ERK and p38 MAPK as early as 3h after treatment and an ERK inhibitor (PD98059) or p38 MAPK inhibitor (SB203580) were found to antagonise the ketone-induced increase in Cx43 protein expression. Thus, ketone bodies up regulate Cx43 expression and GJIC in BAECs via activation of ERK and p38 MAPK. PMID- 24210277 TI - "Food safety on the go": a course for home-delivered meal programs. PMID- 24210278 TI - Accessibility of long-acting reversible contraceptives (LARCs) in Federally Qualified Health Centers (FQHCs). AB - OBJECTIVE(S): This study examines the on-site availability of long-acting reversible contraception (LARC) methods, defined here as intrauterine devices and contraceptive implants, at Federally Qualified Health Centers (FQHCs). We also describe factors associated with on-site availability and specific challenges and barriers to providing on-site access to LARC as reported by FQHCs. STUDY DESIGN: An original survey of 423 FQHC organizations was fielded in 2011. RESULTS: Over two thirds of FQHCs offer on-site availability of intrauterine devices yet only 36% of FQHCs report that they offer on-site contraceptive implants. Larger FQHCs and FQHCs receiving Title X Family Planning program funding are more likely to provide on-site access to LARC methods. Other organizational and patient characteristics are associated with the on-site availability of LARC methods, though this relationship varies by the type of method. The most commonly reported barriers to providing on-site access to LARC methods are related to the cost of stocking or supplying the drug and/or device, the perceived lack of staffing and training, and the unique needs of special populations. CONCLUSION: Our findings indicate that patients seeking care in small FQHC organizations, FQHCs with limited dedicated family planning funding and FQHCs located in rural areas may have fewer choices and limited access to LARC methods on-site. IMPLICATIONS: Despite the presumed widespread coverage of contraceptives for women as a result of provisions in the Affordable Care Act, there is a limited understanding of how FQHCs may redesign their practices to provide on-site availability of LARC methods. This study sheds light on the current state of practice and challenges related to providing LARC methods in FQHC settings. PMID- 24210279 TI - Putting the man in contraceptive mandate. PMID- 24210280 TI - [Gonococcal conjunctivitis in a young woman]. AB - We describe the management of a female patient who developed an uncomplicated unilateral purulent conjunctivitis with no other clinical signs. The typical clinical presentation and Gram stain of the discharge suggested gonococcal conjunctivitis, allowing treatment to be initiated. Indeed, a strain of Neisseria gonorrhoeae resistant to penicillin and tetracycline was isolated. In collaboration with the patient's primary care physician, management included lavage of the infected eye, systemic antibiotic treatment with erythromycin and topical antibiotic treatment with azithromycin, followed by local steroid treatment in response to persistent hyperemia, which was discontinued and replaced by azithromycin again because of recurrent discharge. Eleven days after the first consultation, a complete cure was achieved without sequelae, and a final check to rule out a residual gonococcal carrier state is planned. Gonococcal conjunctivitis, a diagnostic and therapeutic emergency, is a potentially blinding sexually transmitted disease with which general practitioners and ophthalmologists are not well aquainted. Although rare in developed countries, its incidence is rising in parallel with the global recrudescence of gonococcal infections. This case of gonococcal conjunctivitis is discussed as a review of the clinical and biological elements necessary for diagnosis and therapeutic management, which must occur as early as possible, taking into account rapidly increasing gonococcal resistance to antimicrobial therapies, so as to interrupt spread of the disease. PMID- 24210281 TI - [Intraocular foreign body presenting as pseudo-uveitis]. PMID- 24210282 TI - [High-resolution spectral domain OCT images of a corneal epithelial inclusion cyst after amniotic membrane transplantation]. PMID- 24210283 TI - Physical and sexual abuse in orphaned compared to non-orphaned children in sub Saharan Africa: a systematic review and meta-analysis. AB - This systematic review assessed the quantitative literature to determine whether orphans are more likely to experience physical and/or sexual abuse compared to non-orphans in sub-Saharan Africa (SSA). It also evaluated the quality of evidence and identified research gaps. Our search identified 10 studies, all published after 2005, from Zimbabwe, South Africa, Kenya and Uganda. The studies consisted of a total 17,336 participants (51% female and 58% non-orphans). Of those classified as orphans (n=7,315), 73% were single orphans, and 27% were double orphans. The majority of single orphans were paternal orphans (74%). Quality assessment revealed significant variability in the quality of the studies, although most scored higher for general design than dimensions specific to the domain of orphans and abuse. Combined estimates of data suggested that, compared to non-orphans, orphans are not more likely to experience physical abuse (combined OR=0.96, 95% CI [0.79, 1.16]) or sexual abuse (combined OR=1.25, 95% CI [0.88, 1.78]). These data suggest that orphans are not systematically at higher risk of experiencing physical or sexual abuse compared to non-orphans in sub Saharan Africa. However, because of inconsistent quality of data and reporting, these findings should be interpreted with caution. Several recommendations are made for improving data quality and reporting consistency on this important issue. PMID- 24210284 TI - Evaluation of 18F-labeled BODIPY dye as potential PET agents for myocardial perfusion imaging. AB - INTRODUCTION: Despite the great potential of positron emission tomography/computed tomography (PET/CT) in cardiovascular disease imaging, one of the major limitations is the availability of PET probes with desirable half-lives and reasonable cost. In this report, we hypothesized that lipophilic cationic BODIPY dye could be selectively accumulated in cardiac muscle, possibly for the development of novel PET myocardial perfusion imaging (MPI) probes. METHODS: A (18)F-labeled BODIPY dye ([(18)F]1) was synthesized efficiently through a fluoride exchange reaction catalyzed by the Lewis acid tin chloride (SnCl4). The compound was first evaluated by a cellular uptake assay in vitro, followed by biodistribution and microPET imaging studies in vivo. RESULTS: [(18)F]1 was obtained in more than 90% labeling yield, with >98% radiochemical purity. The HEK 293 cellular uptake assay showed that the preferential uptake of [(18)F]1 could be related to the cell membrane potential. The biodistribution data demonstrated high levels of [(18)F]1 accumulation in the heart. In the biodistribution study in mice, the radioactivity uptake in the heart, blood, liver and lung was 3.01 +/ 0.44, 0.39 +/- 0.09, 0.69 +/- 0.07, 1.71 +/- 0.27%ID/g, respectively, at 3h post injection (p.i.). The heart-to-lung and heart-to-liver ratios are 1.76 +/- 0.14 and 4.37 +/- 0.51 at 3h p.i., respectively. Volume-of-interest analysis of the microPET images correlated well with the biodistribution studies in mice. The heart was clearly visualized in normal rats, with 0.72 +/- 0.18, 0.69 +/- 0.18, 0.67 +/- 0.20 and 0.59 +/- 0.17%ID/g uptake at 0.5, 1, 2 and 4h p.i., respectively. CONCLUSIONS: (18)F-labeled BODIPY dye showed good heart uptake and heart-to-blood and heart-to-lung contrast. A (18)F-labeled BODIPY dyes may represent a new category of cationic PET agents for myocardial perfusion imaging. PMID- 24210285 TI - In vivo PET quantification of the dopamine transporter in rat brain with [18F]LBT 999. AB - INTRODUCTION: We examined whether [(18)F]LBT-999 ((E)-N-(4-fluorobut-2-enyl)2beta carbomethoxy-3beta-(4'-tolyl)nortropane) is an efficient positron emission tomography (PET) tracer for the quantification of the dopamine transporter (DAT) in the healthy rat brain. METHODS: PET studies were performed using several experimental designs, i.e. test-retest, co-injection with different doses of unlabelled LBT, displacement with GBR12909 and pre-injection of amphetamine. RESULTS: The uptake of [(18)F]LBT-999 confirmed its specific binding to the DAT. The non-displaceable uptake (BP(ND)) in the striatum, between 5.37 and 4.39, was highly reproducible and reliable, and was decreased by 90% by acute injection of GBR12909. In the substantia nigra/ventral tegmental area (SN/VTA), the variability was higher and the reliability was lower. Pre-injection of amphetamine induced decrease of [(18)F]LBT-999 BP(ND) of 50% in the striatum. CONCLUSIONS: [(18)F]LBT-999 allows the quantification of the DAT in living rat brain with high reproducibility, sensitivity and specificity. It could be used to quantify the DAT in rodent models, thereby allowing to study neurodegenerative and neuropsychiatric diseases. PMID- 24210286 TI - Comparison between two labeled agents in mice using a coinjection-ratio approach in contrast to a conventional group approach. AB - INTRODUCTION: The differences between two agents often need to be accurately defined in vivo. Usually they are injected respectively into two groups of subjects. However, if the two agents do not interact with each other in vivo, a coinjection would serve the same purpose. We believe some individual differences in biodistribution may be circumvented through this approach by calculating organ level ratios. METHODS: A model system of MORF/cMORF pretargeting (MORF/cMORF is a complementary pair of DNA analogues) was employed in connection with an on-going tumor therapeutic project. Human LS174T cells were implanted into the flank of severely immuno-compromised NOD-scid IL2rg(null) mice. The tumor was confirmed to express TAG-72 antigens. At 16 days post tumor inoculation, mice received IV 60 MUg of MORF-conjugated CC49 (an antiTAG-72 antibody), followed 2 days later by a low-mass-dose IV coinjection containing 2.5 MUg of (90)Y-cMORF and 2.5 MUg of (99m)Tc-cMORF. At 3 h post radioactivity injection, the distribution of (99m)Tc was imaged on a SPECT/CT camera and then organs were excised and counted for (90)Y and (99m)Tc. Because the two labeled cMORFs do not react or interact with each other in vivo, the two groups of (90)Y and (99m)Tc data enabled a conventional group comparison. In a new effort, (90)Y/(99m)Tc ratios were calculated. Student's t-test and retrospective power analysis were performed for both approaches. In the new approach, the ratios were set at 1 as the null hypothesis. RESULTS: The Student's t-test in the conventional group approach indicated that the two labeled cMORFs distributed similarly, but significant differences were observed in salivary gland and large intestines. The coinjection ratio approach certainly did not subvert the results of the conventional approach but revealed subtler differences. The P values were reduced, the powers were increased in most organs, and more significant differences were observed. The increased sensitivity was due to the reduced CV%s (SD/average*100%) of the (90)Y/(99m)Tc ratios. Therefore, some individual differences were circumvented and notably the ratio approach differentiated individual differences into ratio correctable and ratio-uncorrectable. CONCLUSIONS: Although the conventional approach is reliable, the coinjection-ratio approach using organ level ratios is more sensitive and therefore is recommended whenever possible. In addition, it differentiates individual differences into "coinjection correctable" and "coinjection uncorrectable". PMID- 24210287 TI - Adult symptomatic and growing arachnoid cyst successfully treated by ventriculocystostomy: a new insight on adult arachnoid cyst history. AB - BACKGROUND: Adult arachnoid cysts are known to be stable and asymptomatic but their history remains undefined. CASE DESCRIPTION: The authors report the case of an 81-year-old woman with progressive hemiplegia and aphasia. CT scan revealed a voluminous left frontotemporal arachnoid cyst with a major mass effect on the midline and contralateral blocked hydrocephalus. Endoscopic ventriculocystostomy was performed with a spectacular neurological improvement. DISCUSSION AND CONCLUSIONS: Symptomatic adult arachnoid cysts are extremely rare. To our knowledge, no similar clinical case of a growing arachnoid cyst in elderly patients has yet been reported in the literature. The mechanisms of cyst enlargement and decompensation still remain undefined and debated. The possibility of adult arachnoid cyst growth has to be considered in clinical practice. Endoscopic ventriculocystostomy is as effective as in paediatric cases. PMID- 24210288 TI - [Focused ultrasound therapy: current status and potential applications in neurosurgery]. AB - High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy. PMID- 24210289 TI - Giant intracranial aneurysms in the paediatric population: Suggested management and a review of the literature. AB - OBJECTIVES: Intracranial aneurysms are rare in children although giant aneurysms more commonly occur in adolescence. The aims of our study were to perform an extensive review of the literature over the past two decades and assess intracranial aneurysm management. METHODS: Based on a Pubmed search, we carried out a review of the literature from 1990 to 2012 regarding giant intracranial aneurysms diagnosed in the paediatric population. This descriptive study concerned clinical presentation, cerebral aneurysm characteristics, therapeutic management procedures and outcome. RESULTS: Forty-six cases were reported in 31 papers. The male/female sex ratio was 1.15, the clinical presentation was a tumour mass syndrome in 56.6%, followed by rupture in 30.4%. The aneurysm location was the posterior circulation in 41.3%, and microsurgical treatment (52.2%) predominated over endovascular coiling (28.3%). CONCLUSION: To date, no evidence-based medicine recommendation has been accepted for the management of rare intracranial aneurysms. Each reported patient was the object of a multidisciplinary clinical decision. Management of this challenging pathology should be performed on a case-to-case basis. PMID- 24210290 TI - Statistical process control using optimized neural networks: a case study. AB - The most common statistical process control (SPC) tools employed for monitoring process changes are control charts. A control chart demonstrates that the process has altered by generating an out-of-control signal. This study investigates the design of an accurate system for the control chart patterns (CCPs) recognition in two aspects. First, an efficient system is introduced that includes two main modules: feature extraction module and classifier module. In the feature extraction module, a proper set of shape features and statistical feature are proposed as the efficient characteristics of the patterns. In the classifier module, several neural networks, such as multilayer perceptron, probabilistic neural network and radial basis function are investigated. Based on an experimental study, the best classifier is chosen in order to recognize the CCPs. Second, a hybrid heuristic recognition system is introduced based on cuckoo optimization algorithm (COA) algorithm to improve the generalization performance of the classifier. The simulation results show that the proposed algorithm has high recognition accuracy. PMID- 24210291 TI - Acupuncture instead of codeine for tonsillectomy pain in children. AB - OBJECTIVES: Severe throat pain can result from tonsillectomy and last up to 10 days in children. Codeine elixir has long been used for pain relief, but has recently been banned by the Food and Drug Administration due to a recently recognized risk of death. We explored acupuncture as an alternative means of pain relief for children and adolescents after tonsillectomy. METHODS: This was a retrospective review of children and adolescents who underwent tonsillectomy over a three-month period. No narcotics were prescribed after surgery. Patients who wanted help with pain relief were offered acupuncture. Perceived pain level was assessed before and after the acupuncture treatment. Following the 10-day recovery for tonsillectomy, patients or their parents were queried as to how long the pain relief from acupuncture intervention was perceived to last. RESULTS: 56 children and adolescents underwent tonsillectomy in the three-month window selected for the retrospective review. 31 of these patients (ranging from 2 to 17 years in age) received an acupuncture intervention for postoperative pain. The mean reported pain level before acupuncture was 5.52 (SD = 2.28) out of 10. This fell to 1.92 (SD = 2.43) after acupuncture. Statistical analysis supported the general conclusion that pain reports decline after acupuncture in the sampled population. However, the limitations of the methodology and the sample suggest that this generalization should be treated as preliminary. 17 patients or their parents provided a post-recovery report for how long they believed the acupuncture intervention lasted. The mean duration of perceived acupuncture benefit was 61.24 h, though the standard deviation was large (64.58 h) with about 30% of patients reporting less than three hours of benefit and about 30% reporting more than 60 h. No adverse effects were observed as a result of acupuncture treatments. CONCLUSIONS: The data tentatively suggest that acupuncture decreases perceived pain in children and adolescents after tonsillectomy. These data - combined with the cost effectiveness, safety and ease of administering acupuncture - suggest that further studies exploring the effectiveness of acupuncture in juveniles after tonsillectomy are merited. PMID- 24210292 TI - Determination of hearing levels in patients with Familial Mediterranean Fever. AB - OBJECTIVE: Familial Mediterranean Fever is the most common congenital, periodic fever condition that affects over 100,000 people worldwide. In the literature, there is limited number of studies about hearing levels in children with Familial Mediterranean Fever. In the present study, we aimed to investigate hearing levels and cochlear functions by using Distortion product Otoacoustic Emission and High Frequency Audiometry (250-20,000 Hz) in pediatric patients with Familial Mediterranean Fever. METHODS: The study included 62 children with Familial Mediterranean Fever and 27 healthy children with similar age and gender. After otoscopic examination, both groups underwent audiological evaluation including High Frequency Audiometry (250-20,000 Hz) and Distortion product Otoacoustic Emissions. The results obtained were assessed among groups. In addition, these results were compared regarding colchicine use, age at the onset of disease and duration of the diseases in the Familial Mediterranean Fever group. RESULTS: Of the Familial Mediterranean Fever patients, 93.5% were on colchicine therapy and mean duration of colchicine use was 19.9 +/- 13.9 months. The mean age at diagnosis was 6.57 +/- 2.86 years (min-max: 2-14) and mean duration of disease was 23 +/- 17 months (min-max: 6-84). Pure tone audiometry values, and hearing levels between 9000 and 20,000 Hz were similar and within normal range in both groups. The Distortion product Otoacoustic Emissions responses at the frequencies of 1020, 2040, 3000, 4080 and 5040 Hz were similar for both groups. CONCLUSION: To the best of our knowledge, this is the first study evaluating hearing levels at the frequencies of 18k Hz and 20k Hz in children with Familial Mediterranean Fever in the literature. In children with Familial Mediterranean Fever, Pure tone audiometry values, hearing values obtained at all frequencies from 250 to 20,000 Hz, and Distortion product Otoacoustic Emissions levels were within normal range. Furthermore, hearing levels were found to be similar to those in healthy children. PMID- 24210293 TI - Muenster Parental Programme empowers parents in communicating with their infant with hearing loss. AB - OBJECTIVE: With the implementation of the Universal Newborn Hearing Screening (UNHS), the age of diagnosis of children with hearing loss (HL) has been steadily declining in the past years. Consequently, there is a need for early educational intervention methods that are suitable for infants at the preverbal level. To meet this need we have developed and evaluated the Muenster Parental Programme (MPP), a responsive parenting programme for parents of children with HL aged 3-18 months. It aims at enhancing the parents' communicative skills towards their child. METHODS: The MPP is introduced following confirmation of a HL. Flanked by two individual counselling sessions, the programme comprises six group sessions and two single training sessions with video feedback. The focus of the programme lies in enhancing parents' responsive behaviour and in reducing inappropriate initiative behaviour. The present study involved 29 parents of 24 children aged 6.6 (mean, range: 3-12) months at the outset of the MPP. The children's degree of HL ranged from moderate to profound. Parents of children with unilateral HL and/or risk for an additional developmental delay were included. The prospective study compared parent communication skills of a trained (N = 15) versus a control group (N = 14) before and after the MPP. For this purpose, instances of responsive behaviour to the signals of the child and total time of initiative behaviour within a 4-min video-sample were measured before and after completion of the study in both groups. RESULTS: Trained parents could enhance their responsiveness to vocal and preverbal signals of the child (Wilcoxon test, p = .002) and also their responsiveness to non-verbal signals (Wilcoxon test, p < .001). Moreover, parents reduced their inappropriate initiative behaviour (related t-test, p < .001). Pre-post comparisons in the control group were non significant. CONCLUSIONS: The increased parental responsiveness to infants with HL is of great importance as these early behaviours underlie later acquisition of speech, language, hearing and social communication skills. The MPP constitutes the first evaluated group concept for parents of infants with HL in the German speaking countries and equally meets the needs of parents and professionals. PMID- 24210294 TI - Spinal cord compression due to undiagnosed thoracic meningioma following lumbar surgery in an elderly patient: a case report. AB - As spinal surgery in elderly patients is becoming increasingly frequent, comorbidities likely to be decompensated after such procedures must be kept in mind. We report here the case of an 82-year-old woman who presented rapidly progressive spinal cord compression following lumbar surgery for radiculopathy. Investigations showed a thoracic intradural extramedullary compressive lesion, which after removal turned out to be a meningioma. We suggest that radiculopathy and non-specific degenerative modifications partially masked this lesion, and that lumbar surgery caused this acute neurological deterioration. Therefore, we advice caution in older patients among whom such ambiguous clinical presentation is frequent. PMID- 24210295 TI - Lessons from Tanzania on the integration of HIV and tuberculosis treatments into methadone assisted treatment. AB - To successfully address HIV and TB in the world, we must address the healthcare needs of key populations, such as drug users, and we must do this urgently. Currently in Tanzania, as in many countries, the care for these medical disorders is separated into disease specific clinical environments. Our consortium began working to integrate HIV and TB clinical services into the methadone program in Dar es Salaam, Tanzania. We present the key lessons learned in this process of integration and the importance of integrating HIV/TB into the methadone program, which serves as a critical anchor for adherence to clinical services. Integrated healthcare for people who use drugs is clearly a long-term goal and different health systems will progress upon this continuum at different rates. What is clear is that every health system that interacts with drug users must aspire to achieve some level of integrated healthcare if the incidence rates of HIV and TB are to decline. PMID- 24210296 TI - Prevalence of IGRA-positivity and risk factors for tuberculosis among injecting drug users in Estonia and Latvia. AB - BACKGROUND: Illegal drug use and HIV are independent risk factors for tuberculosis (TB) among injecting drug users (IDU). Estonia and Latvia have experienced high rates of TB as well as IDU and HIV outbreaks. There is a lack of knowledge about TB among IDUs in these countries. The purpose of the current study was to estimate the prevalence and risk factors of Mycobacterium tuberculosis (MTB) infection among IDUs in Estonia and Latvia. METHODS: Participants for this cross-sectional study were recruited from syringe exchange programmes using respondent-driven sampling. For assessing infection with MTB interferon-gamma release assay (IGRA) was used. RESULTS: The study included 375 participants from Estonia and 313 from Latvia. The prevalence of IGRA-positivity among IDUs was 7.7% in Estonia and 25.6% in Latvia. HIV-prevalence was 62% in Estonia and 23% in Latvia. In both countries, IGRA-positivity rates did not differ between HIV-positive and HIV-negative participants. IGRA-positivity was independently associated with a prior diagnosis of TB in Estonia and with imprisonment (ever within a lifetime) and preceding contact with a TB patient in Latvia. CONCLUSION: Our findings indicate there is an urgent need for a more vigorous approach in providing IDUs with TB screening services. PMID- 24210297 TI - Nanoporous array anodic titanium-supported co-polymeric ionic liquids as high performance solid-phase microextraction sorbents for hydrogen bonding compounds. AB - A nanoporous array anodic titanium-supported co-polymeric ionic liquids (NAAT/PILs) solid-phase microextraction (SPME) fiber was prepared in situ on the titanium wire. NAAT was selected as the substrate, in view of its high surface-to volume ratio, easy preparation, mechanical stability, and rich titanol groups on its surface which can anchor silica coupling agent containing vinyl and then introduce ionic liquid copolymers as sorbents. In this work, 1-vinyl-3-nonanol imidazolium bromide ([C9OHVIm]Br) and 1,4-di(3-vinylimidazolium) butane dibromide ([(VIM)2C4]2[Br]) were synthesized and used as monomer and crosslinker, respectively. Extraction properties of the NAAT/PILs fiber for polar alcohols and volatile fatty acids (VFAs) in aqueous matrix were examined using gaseous sampling-SPME (GS-SPME) and headspace SPME (HS-SPME) mode, respectively. Combining the superior properties of NAAT substrate and the strong hydrogen bond interaction of PILs to polar compounds, the NAAT/PILs SPME fiber showed much higher adsorption affinity to aliphatic alcohols than bare NAAT and pure PILs fibers. The detection limits (LOD) of established GS-SPME-GC-FID method are in the range of 0.35-17.30ngL(-1) with a linear range from 0.01 to 500ngmL(-1). Also, it showed high extraction performance toward volatile fatty acids (VFAs) compounds from aqueous matrix. Under the optimized SPME conditions, wide linear ranges were obtained with correlation coefficients (R(2)) greater than 0.99 and limits of detection were in the range of 0.85-8.74ngL(-1). Moreover, real-world samples were analyzed and good results were obtained. PMID- 24210298 TI - A novel method for the determination of black liquor viscosity by multiple headspace extraction gas chromatography. AB - This work demonstrates a novel method for the determination of viscosity in the concentrated black liquors from pulp mill recovery process. The method is based on the kinetic release of methanol (a vapor tracer) to the headspace in a sample closed vial by a multiple headspace extraction gas chromatographic technique. Both theoretical and empirical models were proposed for establishing the correlation with the reference method. The results showed that the correlation using either of the models is excellent for the tested black liquor samples (at 110 degrees C). The presented method is simple and practical and can be a valuable tool for black liquor viscosity related research and applications. PMID- 24210299 TI - Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: method development and application in hepatocellular carcinoma. AB - Sphingolipids are a family of bioactive molecules with high structural diversity and complexity. They not only serve as integral components of cellular membrane, but also play pivotal roles in signaling and other cellular events. It is desirable for the development of sensitive, robust and structural-specific analytical approaches enabling rapid determination of as many sphingolipid species as possible. Herein we present an analytical method for large-scaled profiling of sphigolipids in human serum, which consisted of an improved extraction protocol using tert-butyl methyl ether combined with mild alkaline hydrolysis, and an ultra high performance reversed-phase liquid chromatography dynamic multiple reaction monitoring-mass spectrometric (RPLC-dynamic MRM-MS) method. In total 84 endogenous sphingolipid species covering six subcategories (i.e. free sphingoid base, dihydroceramide, ceramide, hexosylceramide, lactosylceramide, and sphingomyelin), were separated and quantified in a single run within 10min. A broad linear range over 2.5-4 orders of magnitude (r(2)>0.99), a limit of detection of 0.01-0.17pmol/mL, and a limit of quantitation of 0.02-0.42pmol/mL were obtained for each subcategory. Average recovery of each subcategory was within 85.6-95.6%. Median values of coefficient of variation (CV) of all detected 84 sphingolipids were 3.9% and 6.8% for intraday and interday precision, respectively. This method was exemplarily applied in a study regarding dysregulated sphingolipid homeostasis in hepatocellular carcinoma. The establishment of this method provides a useful tool for serum-based high throughput screening of sphingolipid biomarkers and mechanism investigation of sphingolipid metabolic regulation in human disease. PMID- 24210300 TI - Recent applications of on-line sample preconcentration techniques in capillary electrophoresis. AB - This review highlights recent developments and applications of on-line sample preconcentration techniques in capillary electrophoresis (CE) from 2010 to April 2013. Various preconcentration techniques based on the analyte velocity change in two or three discontinuous solutions system including field-amplified stacking, transient isotachophoresis, pH-mediated stacking, sweeping, and their modified and combined techniques have been employed to enrich and separate biological, environmental, food, toxicological, forensic and nanoparticle samples in CE. More than 170 published research articles collected from Scopus databases from the year 2010 described the on-line sample preconcentration techniques. This review provides comprehensive tables listing the applications of the on-line sample preconcentration techniques with categorizing by the fundamental preconcentration mechanism and application area. PMID- 24210301 TI - Magnetic nanoparticles solid phase extraction for determination of ochratoxin A in cereals using high-performance liquid chromatography with fluorescence detection. AB - A new, simple, fast, and environmental friendly sample preconcentration technique based on the modified Fe3O4 nanoparticles has been developed for extraction, and determination of ochratoxin A (OTA). Magnetic nanoparticles were coated with 3 (trimethoxysilyl)-1-propanethiol and modified by ethylene glycol bis mercaptoacetate. Transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectrometry were used to characterize the adsorbents and the main parameters affecting the extraction and desorption efficiencies, such as pH of sample solution, sample volume, desorption conditions, extraction and desorption times, salt addition, and co-existing interferences have been investigated and established. Under optimal conditions, OTA was extracted and analyzed using high performance liquid chromatography with fluorescence detection. The mobile phase consists of acetonitrile:water:acetic acid (99:99:2, v/v/v) and fluorescence detection was performed with excitation and emission wavelengths at 333 and 477nm, respectively. An enrichment factor of 24 was achieved for OTA with relative standard deviation of <7%. The proposed method was applied to twenty samples of cereals (rice, wheat, and corn). The limits of detection of 0.06, 0.03, and 0.05ngmL(-1) and limits of quantitation of 0.19, 0.11, and 0.15ngmL(-1), were found for rice, wheat, and corn samples, respectively. The recoveries of OTA for spiked samples were ranged from 87 to 93%. PMID- 24210302 TI - Liquid chromatography-full scan-high resolution mass spectrometry-based method towards the comprehensive analysis of migration of primary aromatic amines from food packaging. AB - European Union legislation has established that plastic food contact materials shall not release primary aromatic amines (PAAs), which are toxic compounds and suspected human carcinogens. As valid alternative to existing methods for PAA determination, which are based on spectrophotometric test or targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches, in this study a LC Orbitrap-full scan-high resolution mass spectrometry (HRMS) method was devised and validated for the determination of migration levels of 22 PAAs from food contact materials, thus exploiting the specificity of accurate mass measurement. Direct injection of the simulant (acetic acid 3%, w/v) into the LC-MS system after migration, without any pre-treatment step, makes the developed method of great value for rapid screening analysis of a large number of amines. A very fast and efficient separation (<11min) of PAAs was achieved. Detection limits in the 0.06-0.7MUgkg(-1) range were calculated for 17 out of 22 of the investigated PAAs, however obtaining values within 5.3MUgkg(-1) for the other 5 amines. Good dynamic linear ranges from two to four orders of magnitude (r(2)>=0.990) were obtained and satisfying results were achieved in terms of intra-day (RSDs<10%) and inter-day repeatability (RSDs<17%). Trueness values in the 70+/-1-131+/-5% range proved reliability of the developed method for PAAs quantification also at very low concentration levels. Finally, the method was successfully applied to a range of different real plastic multilayer food packaging materials, noticing in all cases levels below the established limits of detection. PMID- 24210303 TI - Purification of human papillomavirus 16 E6/E7 plasmid deoxyribonucleic acid-based vaccine using an arginine modified monolithic support. AB - The development of efficient plasmid DNA (pDNA) purification processes has fostered therapeutic applications like gene therapy and DNA vaccination. In fact, monolithic supports have emerged as interesting approaches to purify pDNA due to their excellent mass transfer properties and high binding capacity for large biomolecules. The present study describes a method that combines the high selectivity of arginine affinity ligands with the versatility of monoliths to efficiently purify the supercoiled (sc) plasmid HPV-16 E6/E7. Quality control tests indicated that the level of impurities (proteins, endotoxins, gDNA and RNA) in the final plasmid sample was in accordance with the guidelines proposed by regulatory agencies. Breakthrough experiments were designed to compare the dynamic binding capacity of pDNA in the conventional arginine-agarose matrix with the modified monolithic support. The arginine monolith capacity was substantially higher than the conventional arginine-agarose matrix at 10% of breakthrough under the flow rate and pDNA concentration used. Overall, given that the pDNA final product complies with regulatory specifications, this combined support can be the key to obtain an adequate non-viral vaccine against a HPV infection. PMID- 24210304 TI - Possibilities of new generation columns packed with 1.3MUm core-shell particles in gradient elution mode. AB - The aim of this work was to evaluate the practical possibilities in gradient elution mode of a column packed with 1.3MUm core-shell particles recently released on the market. For this purpose, two types of analytes possessing different diffusion coefficients were selected (small molecule and peptide). It appears that the new 1.3MUm material was particularly well suited for fast separations, compared to other existing core-shell particle dimensions in gradient mode. The new material systematically outperforms the other existing ones for peak capacity up to 300 for small molecules and 700 (corresponding to t0=15min) for peptides. Based on these cut-off values, the advantage of column packed with 1.3MUm was much more obvious for peptides vs. small molecules analysis. Further improvements in terms of column mechanical stability and system upper pressure capability could expand the limits of separation speed and efficiency to a different level. Again, because of the current pressure limitation and low permeability, a column length of more than 5-8cm is never desired for small molecules analysis in gradient elution. On the contrary, longer columns were useful for peptide analysis. As example, a column of 28cm packed with 1.3MUm particles provides a peak capacity of 1000 in the case of peptides analysis. All the predicted values were experimentally confirmed using a standardized extract of Ginkgo biloba and a tryptic digest of a monoclonal antibody (Panitumumab). For the plant extract, the better performance was always achieved with a 5cm long column (P=267 and 268 for the 5 and 15cm, respectively, using a gradient time of 10 and 40min, respectively). Finally, in the case of peptide mapping, a 15cm long column packed with 1.3MUm particles was the best choice (P=176 and 311 for the 5 and 15cm, respectively, using a gradient time of 10 and 40min, respectively). PMID- 24210305 TI - Determination of artificial sweeteners in sewage sludge samples using pressurised liquid extraction and liquid chromatography-tandem mass spectrometry. AB - An analytical method for the determination of six artificial sweeteners in sewage sludge has been developed. The procedure is based on pressurised liquid extraction (PLE) with water followed by solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry analysis. After optimisation of the different PLE parameters, extraction with aqueous 500mM formate buffer (pH 3.5) at 80 degrees C during a single static cycle of 21min proved to be best conditions. After a subsequent SPE, quantification limits, referred to dry weight (dw) of sewage sludge, ranged from 0.3ng/g for acesulfame (ACE) to 16ng/g for saccharin (SAC) and neohespiridine dihydrochalcone. The trueness, expressed as recovery, ranged between 72% and 105% and the precision, expressed as relative standard deviation, was lower than 16%. Moreover, the method proved its linearity up to the 2MUg/g range. Finally, the described method was applied to the determination of the artificial sweeteners in primary and secondary sewage sludge from urban wastewater treatment plants. Four of the six studied artificial sweeteners (ACE, cyclamate, SAC and sucralose) were found in the samples at concentrations ranging from 17 to 628ng/g dw. PMID- 24210306 TI - [Celiac disease in children from the northwest of Mexico: clinical characteristics of 24 cases]. AB - BACKGROUND: Celiac disease (CD) is an autoimmune enteropathy induced by dietary wheat gluten that can have serious consequences if not diagnosed and treated early. It is important to be familiar with other alterations associated with gluten ingestion due to the multiplicity of clinical presentations. OBJECTIVES: To describe the most common CD presentation patterns and alterations associated with gluten in children from the northwest region of Mexico, with an incipient knowledge of its prevalence. PATIENTS AND METHODS: Age, sex, family history, and gastrointestinal and extraintestinal symptoms were recorded in 24 patients within the time frame of 2006 to 2010. Biochemical and hematologic data were collected. Anti-gliadin and anti-transglutaminase antibodies were analyzed in all the cases, and haplotypes (HLA-DQ2/DQ8) and duodenal biopsy were evaluated in some of the cases. RESULTS: Of the 24 patients (14 girls and 10 boys), 13 presented with typical CD with symptoms of poor gastrointestinal absorption; 7 patients with a mean age of 5 years presented with atypical CD; 2 had disease onset with gastrointestinal and extraintestinal (neurologic) problems; and 2 with other gluten-related disorders. All of the patients had positive serology; 11/15 presented with HLA-DQ2/DQ8 and 4 with at least one allele; damaged mucosa was observed in the 6 biopsies taken. A third of the patients were anemic, 6 presented with an albumin value of<3.5g/dL, and 4 with mineral deficiencies. A total of 83% of the patients improved with a gluten-free diet. CONCLUSIONS: The presentation patterns were: 1) typical CD, 2) atypical CD, 3) CD with gastrointestinal and extraintestinal (neurologic) symptoms, and 4) gluten-related disorders other than CD. PMID- 24210307 TI - Greater trochanteric pain syndrome negatively affects work, physical activity and quality of life: a case control study. AB - Musculoskeletal injury causes pain and when chronic can affect mental health, employment and quality of life. This study examined work participation, function and quality of life in people with greater trochanteric pain syndrome (GTPS, n=42), severe hip osteoarthritis (OA, n=20) and an asymptomatic group (ASC, n=23). No differences were found between the symptomatic groups on key measures, both were more affected than the ASC group, they had lower quality of life score (p<0.001), Harris Hip Score (p<0.001) and higher Oswestry Disability Index (p<0.001). Participants with GTPS were the least likely to be in fulltime work (prob. GTPS=0.29; OA=0.52; and ASC=0.68). GTPS appears to confer levels of disability and quality of life similar to levels associated with end stage hip OA. PMID- 24210308 TI - Acetabular cup revision combined with tensor facia lata reconstruction for management of massive abductor avulsion after failed total hip arthroplasty. AB - We report on 17 patients with massive abductor avulsions after total hip arthroplasty (THA) treated with medialization of the acetabular component and tensor fascia lata (TFL) reconstruction. All patients had severe limp, positive Trendelenburg sign, and avulsion of the abductor insertion confirmed on MRI. Mean age was 69 years (range, 50-83 years), and mean follow-up period was 36 months (range, 18-78 months). After surgery, 9 patients had no limp (47%), 8 patients had a mild limp, and abductor power improved from mean 2.5/5 to mean 3.8 (P < 0.0001). At latest follow-up, the Harris Hip Score was excellent in 6 hips (37%), good in 7 (43%) hips, and fair or poor in 3 (23%). Two patients with mild limp were not satisfied with their procedure. PMID- 24210309 TI - Anatomic considerations, nomenclature, and advanced cross-sectional imaging techniques for visualization of the cranial nerve segments by MR imaging. AB - Various methods of cross-sectional imaging are used for visualization of the cranial nerves, relying heavily on MR imaging. The success of the MR imaging sequences for visualization of cranial nerves depends on their anatomic context at the point of evaluation. The heterogeneity of opinion regarding optimal evaluation of the cranial nerves is partly a function of the complexity of cranial nerve anatomy. A variety of approaches are advocated and variations in equipment and terminology cloud the field. This article proposes a segmental classification and corresponding nomenclature for imaging evaluation of the cranial nerves and reviews technical considerations and applicable literature. PMID- 24210310 TI - High-resolution CISS MR imaging with and without contrast for evaluation of the upper cranial nerves: segmental anatomy and selected pathologic conditions of the cisternal through extraforaminal segments. AB - The authors review the course and appearance of the major segments of the upper cranial nerves from their apparent origin at the brainstem through the proximal extraforaminal region, focusing on the imaging and anatomic features of particular relevance to high-resolution magnetic resonance imaging evaluation. Selected pathologic entities are included in the discussion of the corresponding cranial nerve segments for illustrative purposes. PMID- 24210311 TI - Lower cranial nerves. AB - Imaging evaluation of cranial neuropathies requires thorough knowledge of the anatomic, physiologic, and pathologic features of the cranial nerves, as well as detailed clinical information, which is necessary for tailoring the examinations, locating the abnormalities, and interpreting the imaging findings. This article provides clinical, anatomic, and radiological information on lower (7th to 12th) cranial nerves, along with high-resolution magnetic resonance images as a guide for optimal imaging technique, so as to improve the diagnosis of cranial neuropathy. PMID- 24210312 TI - Peripheral neuropathy: clinical and electrophysiological considerations. AB - This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field magnetic resonance neurography may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID- 24210313 TI - Magnetic resonance neurography: technical considerations. AB - Proper performance of magnetic resonance neurography (MRN) is essential not only to make the examination easier to interpret but also for its accurate evaluation. This article outlines the technical considerations of MRN, various imaging pulse sequences available on current scanners, as well as their relative advantages and disadvantages. In addition, a guide to the optimal use of high-resolution and high-contrast MRN technique is provided, which will aid clinicians in attaining a good-quality examination. PMID- 24210314 TI - Peripheral MR neurography: approach to interpretation. AB - The magnetic resonance neurography (MRN) examination is rapidly becoming a part of the diagnostic algorithm of patients with peripheral neuropathy; however, because of the technical demands and the lack of required reading skills, the examination is relatively underutilized and is currently limited to a few tertiary care centers. The radiologists with interest in peripheral nerve imaging should be able to perform and interpret this examination to exploit its potential for widespread use. This article outlines the systematic, stepwise approach to its interpretation and a brief discussion of the imaging pitfalls. PMID- 24210315 TI - MR imaging of the brachial plexus. AB - Continuous improvements in magnetic resonance scanner, coil, and pulse sequence technology have resulted in the ability to perform routine, high-quality imaging of the brachial plexus. With knowledge of the anatomy of the plexus, and a familiarity with common pathologic conditions affecting this area, radiologists can provide valuable imaging evaluation of patients with brachial plexus pathologies. PMID- 24210316 TI - High-resolution magnetic resonance neurography in upper extremity neuropathy. AB - The most common sites of nerve entrapment are in the upper extremity, commonly diagnosed based on clinical findings and electrophysiologic studies. Cross sectional imaging modalities, such as ultrasonography and magnetic resonance (MR) imaging, have been used to enhance diagnostic accuracy and provide anatomic mapping of abnormalities. MR neurography offers multiplanar high-resolution imaging of upper extremity nerves as well as adjacent soft tissues, and provides an objective assessment of the neuromuscular anatomy and related abnormalities. This article reviews the normal 3-T MR neurographic appearance of the upper extremity nerves, and abnormal findings related to injury, entrapment, and other pathologic conditions. PMID- 24210317 TI - Magnetic resonance neurography of the pelvis and lumbosacral plexus. AB - Recent advances in magnetic resonance (MR) imaging have revolutionized peripheral nerve imaging and made high-resolution acquisitions a clinical reality. High resolution dedicated MR neurography techniques can show pathologic changes within the peripheral nerves as well as elucidate the underlying disorder or cause. Neurogenic pain arising from the nerves of the pelvis and lumbosacral plexus poses a particular diagnostic challenge for the clinician and radiologist alike. This article reviews the advances in MR imaging that have allowed state-of-the art high-resolution imaging to become a reality in clinical practice. PMID- 24210318 TI - High-resolution magnetic resonance imaging of the lower extremity nerves. AB - Magnetic resonance (MR) imaging of the nerves, commonly known as MR neurography is increasingly being used as noninvasive means of diagnosing peripheral nerve disease. High-resolution imaging protocols aimed at imaging the nerves of the hip, thigh, knee, leg, ankle, and foot can demonstrate traumatic or iatrogenic injury, tumorlike lesions, or entrapment of the nerves, causing a potential loss of motor and sensory function in the affected area. A thorough understanding of normal MR imaging and gross anatomy, as well as MR findings in the presence of peripheral neuropathies will aid in accurate diagnosis and ultimately help guide clinical management. PMID- 24210319 TI - Magnetic resonance neurography of peripheral nerve tumors and tumorlike conditions. AB - Peripheral nerve enlargement may be seen in multiple conditions including hereditary or inflammatory neuropathies, sporadic or syndromic peripheral nerve sheath tumors, perineurioma, posttraumatic neuroma, and intraneural ganglion. Malignancies such as neurolymphoma, intraneural metastases, or sarcomas may also affect the peripheral nervous system and result in nerve enlargement. The imaging appearance and differentiating factors become especially relevant in the setting of tumor syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. This article reviews the typical magnetic resonance neurography imaging appearances of neurogenic as well as nonneurogenic neoplasms and tumorlike lesions of peripheral nerves, with emphasis on distinguishing factors. PMID- 24210320 TI - Peripheral nerve surgery: primer for the imagers. AB - Peripheral nerve surgery represents a broad field of pathologic conditions, medical specialties, and anatomic regions of the body. Anatomic understanding of hierarchical nerve structure and the peripheral nervous system aids diagnosis and management of nerve lesions. Many peripheral nerves coalesce into organized arrays, including the cervical, brachial, and lumbosacral plexuses, controlling motor and sensory functions of the trunk and extremities. Individual or groups of nerves may be affected by various pathologic conditions, including trauma, entrapment, tumor, or iatrogenic damage. Current research efforts focus on enhancing the peripheral nerve regenerative process by targeting Schwann cells, nerve growth factors, and nerve allografts. PMID- 24210321 TI - Magnetic resonance neurography-guided nerve blocks for the diagnosis and treatment of chronic pelvic pain syndrome. AB - Magnetic resonance (MR) neurography - guided nerve blocks and injections describe a techniques for selective percutaneous drug delivery, in which limited MR neurography and interventional MR imaging are used jointly to map and target specific pelvic nerves or muscles, navigate needles to the target, visualize the injected drug and detect spread to confounding structures. The procedures described, specifically include nerve blocks of the obturator nerve, lateral femoral cutaneous nerve, pudendal nerve, posterior femoral cutaneous nerve, sciatic nerve, ganglion impar, sacral spinal nerve, and injection into the piriformis muscle. PMID- 24210322 TI - The role of magnetic resonance neurography in the postoperative management of peripheral nerve injuries. AB - Diagnostic limitations exist in the assessment of postoperative nerve regeneration. This article describes the role of available methods, such as clinical assessment, electrophysiologic studies, and magnetic resonance neurography in the postoperative evaluation of peripheral nerve repairs. PMID- 24210323 TI - Magnetic resonance neurography: diffusion tensor imaging and future directions. AB - Magnetic resonance (MR) neurography has progressed in the past 2 decades because of rapid technological developments in both hardware and software. In addition to improvements in high-resolution anatomic pulse sequences, functional techniques are becoming feasible. This article presents the current state-of-the-art three dimensional anatomic techniques, discusses the advantages of functional techniques being exploited, and portrays novel contrast types and molecular techniques that are under development and promise a bright future for this rapidly evolving technique. PMID- 24210324 TI - Magnetic resonance neurography research: evaluation of its effectiveness. AB - Magnetic resonance neurography (MRN) is a specialized technique that is rapidly becoming part of the diagnostic algorithm of peripheral nerve pathology. However, in order for this modality to be considered appropriate, its value compared with current methods of diagnosis should be established. Therefore, radiologists involved in MRN research should use appropriate methodology to evaluate MRN's effectiveness with a multidisciplinary approach. This article reviews the various tiers of research available to assess the clinical value of a diagnostic modality with an emphasis on how to evaluate the impact of MRN on diagnostic thinking and therapeutic decisions. PMID- 24210325 TI - MR neurography. PMID- 24210326 TI - MR neurography. PMID- 24210327 TI - Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection. AB - BACKGROUND: The differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis. OBJECTIVES: We investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB. STUDY DESIGN: A total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n=21), patients with HBeAg-negative hepatitis (n=95), HBeAg-positive hepatitis (n=141) and liver cirrhosis (n=82). RESULTS: Serum M30-antigen levels were correlated significantly not only with AST (r=0.544, p<0.001) and ALT (r=0.315, p<0.001) and but also inflammatory grading score on liver biopsy (r=0.240, p<0.001). Serum M30-antigen level in HBeAg negative CHB was significantly higher than that of inactive HBV carrier (399.78 U/L vs 148.90 U/L, p<0.001). Multivariate analysis showed that AST (p<0.001), albumin (p=0.009) and M30-antigen (p=0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344 U/L) and AST (>78 IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value. CONCLUSIONS: Serum M30 antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients. PMID- 24210328 TI - Designation of human adenovirus types based on sequence data: an unfinished debate. PMID- 24210329 TI - Human papillomavirus type 56 polymorphism in Canadian women with and without cervical lesions. AB - BACKGROUND: The genomic diversity of high-risk human papillomaviruses (HPV) has been associated with viral persistence and HPV-induced lesions. Studies on HPV56 persistence are still pending. OBJECTIVE: To assess the association between HPV56 polymorphism and HPV56 persistence and presence of high-grade cervical intraepithelial neoplasia (CIN2,3) or cancer. STUDY DESIGN: HPV56-positive cervical specimens from 204 women selected from a total of 4669 participants recruited in 5 epidemiological studies (parent studies) were further analyzed by PCR-sequencing of the long control region (LCR). RESULTS: Of the 81 women followed prospectively in cohort studies who could be classified, 34 had persistent and 47 had transient HPV56 infections. Variant HPV56-LCR-MTL-21 was detected more frequently in persistent infections (52.9%, 95% CI: 36.7-68.6%) than in transient infections (25.5%, 95% CI: 15.1-39.4). Considering only women recruited in a cohort of women infected or at high risk for HIV infection, infection with variant HPV56-LCR-MTL-21 (OR=4.4, 95% CI: 1.3-14.5) was significantly associated with HPV56 persistence controlling in multivariate analysis for high risk HPV detection and HIV infection. A variation at nucleotide 7800 in HPV56-LCR-MTL-21 resulted in the loss of a binding site for Elf-1 embedded in one of the E2 binding sites, a potential activator or repressor of expression of the HPV genome. HPV56 polymorphism was not associated with CIN2,3 or cancer in women enrolled in cross-sectional and case-control studies. CONCLUSION: Polymorphism in HPV56 may influence the risk that infections with this type will persist. PMID- 24210331 TI - Immune response of heifers against a Staphylococcus aureus CP5 whole cell and lysate vaccine formulated with ISCOM Matrix adjuvant. AB - Staphylococcus aureus is the most frequently isolated pathogen from bovine intramammary infections worldwide. Commercially available vaccines for mastitis control are composed either of S. aureus lysates or whole-cells formulated with traditional adjuvants. We recently showed the ability of a S. aureus CP5 whole cell vaccine adjuvanted with ISCOM Matrix to increase specific antibodies production in blood and milk, improving opsonic capacity, compared with the same vaccine formulated with Al(OH)3. However, there is no information about the use of ISCOM Matrix for the formulation of bacterial lysates. The aim of this study was to characterize the innate and humoral immune responses induced by a S. aureus CP5 whole-cell or lysate vaccine, formulated with ISCOM Matrix after immunization of pregnant heifers. Both immunogens stimulated strong humoral immune responses in blood and milk, raising antibodies that increased opsonic capacity. Lysate formulation generated a higher and longer lasting antibody titer and stimulated a higher expression of regulatory and pro-inflammatory cytokines compared with the whole-cell vaccine. PMID- 24210330 TI - Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa. AB - BACKGROUND: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. OBJECTIVES: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. STUDY DESIGN: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n=467) and HIV-negative (n=2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. RESULTS: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV infected women with CD4 cell counts less than 200 cells/MUl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07-1.59), multiple HPV types (PRa 1.52; 95% CI 1.14-2.01), and HPV-16 (PRa 9.00; 95% CI 1.66-48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45-3.24) compared to those with CD4 counts 500 cells/MUl or above. CONCLUSION: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations. PMID- 24210332 TI - Laparoscopic greater curvature plication: surgical techniques and early outcomes of a Chinese experience. AB - BACKGROUND: Laparoscopic greater curvature plication (LGCP) is a novel restrictive bariatric procedure that can reduce the gastric volume by infolding the gastric greater curvature without gastrectomy. The objective of this study was to describe the surgical technique of LGCP and validate the efficacy and safety of LGCP for the treatment of obesity in obese Chinese patients with a relatively low body mass index (BMI). METHODS: Twenty-two obese patients (mean age 33.8+/-6.0 years; mean BMI 37.0+/-7.0 kg/m(2)) underwent LGCP between September 2011 and September 2012. After dissecting the greater omentum and short gastric vessels, the gastric greater curvature plication with 2 rows of nonabsorbable suture was performed under the guidance of a 32-F bougie. The data were collected during follow-up examinations performed at 1, 3, 6, and 12 months postoperatively. RESULTS: All procedures were performed laparoscopically. The mean operative time was 84.1 minutes (50-120 min), and the mean length of hospital stay was 3.8 days (2-10 d). There were no deaths or postoperative major complications that needed reoperation. The mean percentage of excess weight loss (%EWL) was 22.9%+/-6.9%, 38.6%+/-9.8%, 51.5%+/-13.5%, and 61.1%+/-15.9% at 1, 3, 6, and 12 months postoperatively. At 6 months, type 2 diabetes was in remission in 2 (50%) patients, hypertension in 1 (33.3%) patient, and dyslipidemia in 11 (78.6%) patients. Decreases in the index for homeostasis model assessment of insulin resistance (HOMA-IR) and in insulin and glucose concentrations were observed. CONCLUSIONS: The early outcomes of LGCP as a novel treatment for obese Chinese with a relatively low BMI are satisfactory with respect to the effectiveness and low incidence of major complications. Additional long-term follow-up and prospective, comparative trials are still needed. PMID- 24210334 TI - Hemodynamic impact and outcome of permanent pacemaker implantation following transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation (TAVI) frequently requires postprocedural permanent pacemaker (PPM) implantation. We evaluated clinical and hemodynamic impact of PPM after TAVI. Clinical and echocardiographic data were retrospectively analyzed in 230 consecutive patients who underwent TAVI and echocardiography at baseline and after 6 months. Echocardiographic parameters included left ventricular ejection fraction (LVEF), left ventricular (LV) stroke volume, early mitral velocity/annulus velocity ratio (E/e'), right ventricular index of myocardial performance, systolic pulmonary artery pressure (SPAP), and aortic, mitral, and tricuspid regurgitation grades. Clinical outcomes included 2 year survival and cardiovascular and PPM-related event-free survival. The Medtronic CoreValve and Edwards Sapien prosthesis were used in 201 and 29 patients, respectively. PPM was required in 58 patients (25.4%). Two-year and event-free survival rates were similar between patients with and without PPM. At 6 months, patients with PPM demonstrated attenuated improvement in LVEF (-0.9 +/- 8.7% vs 2.3 +/- 10.8%, respectively, p = 0.03) and LV stroke volume (-2 +/- 16 vs 4 +/- 10 ml/m(2), respectively, p = 0.015), a trend toward smaller reduction in systolic pulmonary artery pressure (-1 +/- 12 vs -6 +/- 10 mm Hg, respectively, p = 0.09), and deterioration of right ventricular index of myocardial performance ( 3 +/- 17% vs 5 +/- 26%, respectively, p = 0.05). The differences in post-TAVI aortic, mitral, and tricuspid regurgitation grades were insignificant. In conclusion, PPM implantation after TAVI is associated with reduced LVEF and impaired LV unloading. However, this unfavorable hemodynamic response does not affect the 2-year clinical outcome. The maintenance of clinical benefit appears to be driven by TAVI-related recovery of LV and right ventricular performance that mitigates unfavorable impact of PPM. PMID- 24210333 TI - Left ventricular hypertrophy patterns and incidence of heart failure with preserved versus reduced ejection fraction. AB - Higher left ventricular (LV) mass, wall thickness, and internal dimension are associated with increased heart failure (HF) risk. Whether different LV hypertrophy patterns vary with respect to rates and types of HF incidence is unclear. In this study, 4,768 Framingham Heart Study participants (mean age 50 years, 56% women) were classified into 4 mutually exclusive LV hypertrophy pattern groups (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) using American Society of Echocardiography-recommended thresholds of echocardiographic LV mass indexed to body surface area and relative wall thickness, and these groups were related to HF incidence. Whether risk for HF types (HF with reduced ejection fraction [<45%] vs preserved ejection fraction [>=45%]) varied by hypertrophy pattern was then evaluated. On follow-up (mean 21 years), 458 participants (9.6%, 250 women) developed new-onset HF. The age- and gender-adjusted 20-year HF incidence increased from 6.96% in the normal left ventricle group to 8.67%, 13.38%, and 15.27% in the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups, respectively. After adjustment for co-morbidities and incident myocardial infarction, LV hypertrophy patterns were associated with higher HF incidence relative to the normal left ventricle group (p = 0.0002); eccentric hypertrophy carried the greatest risk (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.41 to 2.54), followed by concentric hypertrophy (HR 1.40, 95% CI 1.04 to 1.87). Participants with eccentric hypertrophy had a higher propensity for HF with reduced ejection fraction (HR 2.23, 95% CI 1.48 to 3.37), whereas those with concentric hypertrophy were more prone to HF with preserved ejection fraction (HR 1.66, 95% CI 1.09 to 2.51). In conclusion, in this large community-based sample, HF risk varied by LV hypertrophy pattern, with eccentric and concentric hypertrophy predisposing to HF with reduced and preserved ejection fraction, respectively. PMID- 24210335 TI - Outcome of transcatheter aortic valve implantation in patients with low-gradient severe aortic stenosis and preserved left ventricular ejection fraction. AB - We aimed to evaluate the clinical and hemodynamic impact of transcatheter aortic valve implantation in patients with typical low-gradient severe aortic stenosis (LGSAS) and at high operative risk for surgical valve replacement. Prospectively collected clinical and echo Doppler data were retrospectively analyzed in 112 and 86 patients, respectively. Follow-up period was 31 months (21 to 38). Thirty eight patients died; combined long-term cardiovascular events were identified in 68 patients. The 30-day mortality rate was 2.4% in patients with typical severe aortic stenosis (AS) and 3.3% in patients with LGSAS (p = 1.0). Two-year survival rate was 77 +/- 5% for the former (n = 82) and 68 +/- 8% for the latter (n = 30; hazard ratio 1.4, 95% confidence interval 0.7 to 2.7 for LGSAS; p = 0.3). Two year cardiovascular event-free survival rates were 56.5 +/- 5.0% and 48.4 +/- 9.0%, respectively, (hazard ratio 1.4, 95% confidence interval 0.78 to 2.3 for LGSAS; p = 0.25). Patients with typical severe AS (n = 64) and those with LGSAS (n = 23) demonstrated similar increases in left ventricular ejection fraction and stroke volume (7 +/- 10% vs 6 +/- 6% and p = 0.67; 12 +/- 22% vs 12 +/- 16%, p = 0.88, respectively) and reduction in systolic pulmonary artery pressure (5 +/- 14 vs 5 +/- 9 mm Hg, respectively, p = 0.83). In conclusion, transcatheter aortic valve implantation appears to result in similar hemodynamic and long-term clinical outcomes for high-risk surgical patients with LGSAS as those with typical severe AS. PMID- 24210336 TI - Corneal enlargement without optic disk cupping in children with recessive CYP1B1 mutations. AB - Corneal enlargement during the first 3 years of life can be a sign of early childhood glaucoma and optic nerve head cupping is a useful confirmatory finding. We report 3 children with corneal enlargement without optic nerve head cupping who had recessive CYP1B1 mutations, the most common identifiable cause of primary congenital glaucoma. One child later developed unilateral Haab striae, still in the absence of optic disk cupping. These cases illustrate that CYP1B1-related corneal changes can occur in young children without visible optic nerve head damage. PMID- 24210337 TI - The importance of electrophysiology in revealing a complete homozygous deletion of KCNV2. AB - Visual electrophysiology is an important ancillary investigation in children with poor vision and nystagmus. Cone dystrophy with supranormal rod electroretinogram (KCNV2 retinopathy) has pathognomonic electrophysiology findings that, if identified, direct molecular genetic testing. We report the case of a 6-year-old boy with typical electrophysiology findings of KCNV2 retinopathy but with abnormal cone dysfunction compared to other patients with mutations in KCNV2. Molecular genetic testing revealed complete homozygous deletion of KCNV2. To our knowledge, this is the first such report. The greater cone dysfunction seen in this case suggests a phenotypic link to the genetic changes. PMID- 24210338 TI - Accuracy of vision screening. PMID- 24210339 TI - Visual outcome after Descemet's stripping automated endothelial keratoplasty in an 8-month-old with congenital hereditary endothelial dystrophy. AB - Descemet's stripping automated endothelial keratoplasty (DSAEK) has rapidly become the standard of care for endothelial dysfunction of the cornea in adults. There are few reports of DSAEK in children and infants, mainly because most pediatric corneal opacities are full-thickness and therefore not amenable to lamellar procedures but also because of the unique difficulties of performing this procedure in the youngest patients. We report the case of an 8-month-old girl who underwent DSAEK for congenital hereditary endothelial dystrophy. At 24 months' follow-up, her visual acuity was 20/40 in the operated eye. To our knowledge, this is the first report of an objective visual outcome in a child with DSAEK performed in infancy. PMID- 24210340 TI - Inadvertent intrastromal injection of ophthalmic viscoelastic. AB - Viscoelastic is an ophthalmic viscosurgical device used to protect ocular tissue and maintain intraocular space during surgical procedures such as cataract removal. To date, the only cases published regarding inadvertent viscosurgical device injection have caused Descemet's membrane detachments. We report the case of a 4-year-old girl who underwent complicated lensectomy with prior history of uveitis and posterior synechia in which intrastromal ophthalmic viscoelastic was inadvertently injected into the stroma, leaving an off-centered opacity. At the time of surgery, no Descemet's membrane detachment was seen. The lensectomy and planned anterior vitrectomy were performed without complication and visual acuity has improved from 20/200 preoperatively to 20/70 at 3 months' follow-up. The corneal opacity resolved within 1 week of surgery, with no evidence of residual visual impairment. PMID- 24210341 TI - A case report of torpedo maculopathy in an African boy. AB - We describe a case report of torpedo maculopathy in a young African boy. Ophthalmic examination revealed normal visual acuity and a characteristic unilateral retinal lesion with the typical appearance on ocular coherence tomographic imaging, fluorescein angiography, and visual fields testing. PMID- 24210342 TI - Isolated oculomotor nerve palsy in a child caused by an internal carotid aneurysm. AB - Common causes for acquired isolated oculomotor nerve palsy in children are trauma, inflammation, and neoplasia. We report a case of isolated oculomotor nerve palsy in a 13-year-old boy secondary to intracranial carotid aneurysm. PMID- 24210343 TI - Scedosporium prolificans endogenous endophthalmitis. AB - Scedosporium prolificans is an opportunistic fungus with a predilection for sepsis and endophthalmitis in immunocompromised patients. We report a case of endogenous S. prolificans endophthalmitis in a 9-year-old girl following chemotherapy for acute myeloid leukemia. She achieved an excellent visual outcome following intensive antifungal therapy. PMID- 24210344 TI - Transient leopard spot corneal endothelial staining with trypan blue during cataract surgery in a child with congenital rubella syndrome. AB - We report the complication of corneal endothelial staining with trypan blue that limited the surgical view during cataract extraction in a 10-month-old boy. The boy had presented with a pigmentary retinopathy, microphthalmia, and a dense, white, unilateral congenital cataract. He was suspected of having, and was later diagnosed with, congenital rubella syndrome. We hypothesize that the corneal staining may have resulted from virally induced corneal endothelial damage. To our knowledge, this is the first reported case of trypan blue adversely affecting congenital cataract surgery. PMID- 24210345 TI - Unilateral recalcitrant glaucoma associated with cytomegalovirus in an immunocompromised child with Wiskott-Aldrich syndrome. AB - We report a case of anterior uveitis and unilateral recalcitrant glaucoma in an immunocompromised 6-year-old boy diagnosed with Wiskott-Aldrich syndrome who presented with elevated intraocular pressure (IOP), mild anterior uveitis, and unilateral acute glaucoma. Polymerase chain reaction from the aqueous was positive for cytomegalovirus (CMV). After initially responding to ganciclovir, the IOP rose again. With worsening optic nerve status, the patient underwent glaucoma filtration surgery with mitomycin C, and a postoperative regimen for CMV retinitis was initiated. PMID- 24210346 TI - Incidence of amblyopia risk factors in children with nasolacrimal duct obstruction. AB - Previously published research suggested that children with nasolacrimal duct obstruction and amblyopia risk factors on initial examination often develop clinical amblyopia. The present study reports the incidence of clinical amblyopia in children presenting with nasolacrimal duct obstruction but no amblyopia risk factors. PMID- 24210347 TI - Using autofluorescence to detect optic nerve head drusen in children. AB - PURPOSE: To assess the efficacy of using autofluorescence to identify optic nerve head drusen (ONHD) in children. METHODS: We conducted a cross-sectional, descriptive study of subjects <18 years of age with possible pseudopapilledema due to ONHD. B-scan ultrasonography was considered the gold standard diagnostic technique. All participants underwent an extensive ophthalmic examination that included fundus color photography, autofluorescence analysis, and B-scan echography. ONHD were classified as visible or hidden. Autofluorescence images were analyzed by three observers who were masked to the results of B-scan ultrasonography. RESULTS: A total of 24 children with pseudopapilledema were included. B-scan ultrasonography confirmed ONHD in 32 eyes of 18 patients (9 boys). Mean patient age was 12 years (range, 7-17 years). ONHD was bilateral in 14 patients; unilateral in 4. The majority of the drusen were hidden (26 of 32 eyes). Analysis of autofluorescence patterns identified the drusen in 94% of cases (30 of 32 eyes): visible, 100%; hidden, 92%. Interobserver agreement was high (kappa = 0.91, kappa = 0.96, kappa = 0.89). CONCLUSIONS: In this study cohort, autofluorescence proved a safe, fast, and reliable technique for identifying ONHD in children. PMID- 24210348 TI - Three-muscle surgery for very large-angle constant exotropia. AB - PURPOSE: To report the outcomes of surgery on three horizontal muscles for very large-angle constant exotropia. METHODS: In this prospective case series, consecutive adult patients with primary constant exotropia with angles >=120(Delta) underwent strabismus surgery on three horizontal muscles. Surgery consisted of lateral rectus recession of 10-15 mm on the fixing eye in addition to lateral rectus recession of 9-13 mm and medial rectus resection of 6.5-9 mm on the nonfixing eye. The mean follow-up period was >6 months. Success was defined as horizontal eso- or exodeviations of <=10(Delta). RESULTS: A total of 23 patients were included. The mean age at surgery was 30.4 +/- 9.3 years (range, 16 52). The mean preoperative near exodeviation was 128(Delta) +/- 9.8(Delta); the mean preoperative distance exodeviation, 130(Delta) +/- 10.4(Delta). The mean follow-up period was 8.1 +/- 1.4 months. At the last follow-up, 19 of the 23 cases (83%) were successfully aligned. At final follow-up examination, the mean postoperative exodeviation was 5(Delta) +/- 4.2(Delta) (near) and 5(Delta) +/- 4.3(Delta) (distance); no patient had diplopia on lateral gazes. CONCLUSIONS: In this patient cohort, surgery on three-muscle surgery for very large-angle exotropia successfully restored alignment in primary gaze in over 80% of cases without inducing symptomatic abduction deficits. PMID- 24210349 TI - Phytotoxkit/Phytotestkit and Microtox(r) as tools for toxicity assessment of sediments. AB - The aim of the study was to use bioassays to evaluate the toxicity of pore water, sediments and sediments elutriates. Furthermore, a possible relationship between observed toxicity and results of chemical analysis was examined. Sediment (0-10 cm) samples were collected from 21 locations in Zeslawice reservoir, Southern Poland using an Ekman sampler. Toxicity assessment of the sediment and pore water samples was performed using direct-contact tests Phytotoxkit/Phytotestkit and Microtox(r). Inhibition of seed germination in the test plants was from -25 to 38 percent for sediment and from 0 to 50 percent for pore water, whereas inhibition of root growth was within a range from -42 to 37 percent for sediment and from 49 to 37 percent for pore water. Depending on the sediments, Vibrio fischeri luminescence inhibition was from -18 to 40 percent for sediments elutriates and from -12 to 28 percent for pore water. The toxicity tests showed a positive correlation between metals and the root growth inhibition in Lepidium sativum and Sinapis alba as well as the luminescence inhibition in V. fischeri. No significant correlations were found between the inhibition of luminescence and the phytotoxicity assays, so these analyses do not show a similar sensitivity to toxicants in the sediments. While estimating the sensitivity of the performed biotests, the highest number of toxic responses was recorded in the Microtox(r) test towards V. fischeri. Among the plant species, Sorghum saccharatum appears to be the most sensitive plant species. Most of the examined sediment samples (67 percent) were classified as class II (low-toxic samples, low acute hazard) and 33 percent of the examined samples were class I (no essential toxic effect, non toxic sample, no acute hazard) in terms of toxicity. Most of the pore water samples (71 percent) were also classified as class II. PMID- 24210350 TI - Toxic effects of three strobilurins (trifloxystrobin, azoxystrobin and kresoxim methyl) on mRNA expression and antioxidant enzymes in grass carp (Ctenopharyngodon idella) juveniles. AB - The strobilurins are used widely in the world as effective fungicidal agents to control Asian soybean rust. In this study, the early life stage of grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China, was chosen to measure the acute toxicity of three common strobilurin derived fungicides (trifloxystrobin (TFS), azoxystrobin (AZ) and kresoxim-methyl (KM)). As endpoints, normal developmental parameters (lethal concentration (LC50) and average heart rate), expression of relative genes, and three antioxidant enzyme activities in the developing juveniles were recorded during a 48 h exposure. The results revealed that values of LC50 were TFS 0.051 (0.046-0.058) mg L-1, AZ 0.549 (0.419-0.771) mg L-1 and KM 0.338 (0.284-0.407) mg L-1 for juveniles. For the potential toxicity mechanisms, these three fungicides increased catalase (CAT) and peroxidase (POD) activity and decreased superoxide dismutase (SOD) activity, significantly inhibited expressions of three growth related genes (IGF-1, IGF-2 and GHR) and two energy-related-genes (CCK and PYY), and caused pronounced up-regulation a stress-gene (HSP70). The present study demonstrated potential toxic effects of TFS, AZ and KM on the early development of C. idella. Overall, three strobilurins (TFS, AZ and KM) might cause serious damages to the aquatic species; therefore, their pollution supervision in water ecological environment should be strengthened. PMID- 24210351 TI - Accumulation and health risk of heavy metals in a plot-scale vegetable production system in a peri-urban vegetable farm near Nanjing, China. AB - Accumulation and potential health risk of cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn) in a plot-scale vegetable production peri-urban area near Nanjing city, China was investigated through element balance method, model simulation and dietary risk assessment. The heavy metals accumulated in the surface soils were due to long-term and heavy application of organic fertilizers, among which the accumulation of Cu and Zn were greater than those of Cd and Pb. The result of a mass balance model simulation indicated that intensive vegetable production would result in accumulation of Cd, Pb, Cu and Zn in soils exceeding the target values in 55, 36, 34 and 71 years, respectively. The estimated dietary intakes of Cd, Pb, Cu, and Zn were far below the tolerable limits and the hazard quotient values were below one for both children and adults. Although there is no imminent health risk from heavy metals through vegetable consumption, more attention should be paid to the long-term accumulation and risk, especially for children. PMID- 24210352 TI - A beneficial role for immunoglobulin E in host defense against honeybee venom. AB - Allergies are widely considered to be misdirected type 2 immune responses, in which immunoglobulin E (IgE) antibodies are produced against any of a broad range of seemingly harmless antigens. However, components of insect venoms also can sensitize individuals to develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. We found that mice injected with amounts of honeybee venom similar to that which could be delivered in one or two stings developed a specific type 2 immune response that increased their resistance to subsequent challenge with potentially lethal amounts of the venom. Our data indicate that IgE antibodies and the high affinity IgE receptor, FcepsilonRI, were essential for such acquired resistance to honeybee venom. The evidence that IgE-dependent immune responses against venom can enhance survival in mice supports the hypothesis that IgE, which also contributes to allergic disorders, has an important function in protection of the host against noxious substances. PMID- 24210354 TI - Antecedent events as predictive variables for behavioral function. AB - Challenging behavior is one of the largest barriers to ensuring that people with intellectual disabilities (ID) are able to participate in the community. These difficulties have become one of the main causes of social exclusion. The research into and treatment of challenging behavior has usually involved the identification of its function and the manipulation of the events or environmental conditions that influence its occurrence (antecedent variables). The present research explores the relationship between antecedents and behavioral function and the extent to which antecedent variables may act as predictors of behavioral function. This relationship is explored using two standardized instruments: Questions About Behavioral Function and Contextual Assessment Inventory. Data from the validation of these instruments for the Spanish population involved 300 participants with ID and 328 challenging behaviors. The results suggest that social/cultural variables are most related to challenging behavior, whereas biological variables seem to only be related to physically maintained behavior. PMID- 24210353 TI - Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity. AB - Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin. PMID- 24210355 TI - Linking social behaviour and anxiety to attention to emotional faces in Williams syndrome. AB - The neurodevelopmental disorder Williams syndrome (WS) has been associated with a social phenotype of hypersociability, non-social anxiety and an unusual attraction to faces. The current study uses eye tracking to explore attention allocation to emotionally expressive faces. Eye gaze and behavioural measures of anxiety and social reciprocity were investigated in adolescents and adults with WS when compared to typically developing individuals of comparable verbal mental age (VMA) and chronological age (CA). Results showed significant associations between high levels of behavioural anxiety and attention allocation away from the eye regions of threatening facial expressions in WS. The results challenge early claims of a unique attraction to the eyes in WS and suggest that individual differences in anxiety may mediate the allocation of attention to faces in WS. PMID- 24210356 TI - The identification and measurement of autistic features in children with septo optic dysplasia, optic nerve hypoplasia and isolated hypopituitarism. AB - This study aimed to highlight the occurrence of autism spectrum disorders (ASDs) in children with septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH). A cross-sectional study was designed, including 28 children with SOD and 14 children with ONH. Clinician diagnosis of ASD was reported in 14 children. The Social Communication Questionnaire (SCQ) reported that 23 children met the cut off point for ASD, and 9 children met the cut-off point for autism. Greater levels of intellectual disability and visual loss were reported in children with ASD in comparison to those without ASD, but, of the two, intellectual disability was a better predictor for ASD. The SCQ lost its sensitivity and specificity in children who had greater visual loss which highlights a requirement for a measure that is sensitive to visual loss. It is also recommended that children with SOD/ONH would benefit from routine screening for ASDs. PMID- 24210357 TI - "Piece" of mind: end of life in the intensive care unit statement of the Belgian Society of Intensive Care Medicine. PMID- 24210358 TI - Using biofilm as a novel approach to assess stormwater treatment efficacy. AB - Contaminants associated with stormwater are among the leading causes of water quality impairment in urban streams. Multiple device treatment systems are commonly installed with the aim of reducing contaminant loads within stormwater discharge. However, the in situ performance of such systems remains poorly understood. We investigated the efficacy of an advanced stormwater treatment system by monitoring biofilm associated metals and biofilm bacterial community composition at multiple locations through the treatment system (which included rain gardens, grassy swales, a stormwater filter and a wetland) and in the receiving stream above and below the stormwater discharge. Changes in bacterial community composition were assessed by Automated Ribosomal Intergenic Spacer Analysis (ARISA) and concentrations of biofilm associated metals monitored by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Significant differences in bacterial community composition were detected throughout the stormwater network. Bacterial communities gradually changed towards a community more similar to that within the receiving stream and the discharge of treated stormwater had little effect on the composition of bacterial communities in the receiving stream, suggesting the effective conditioning of water quality by the treatment system. Concentrations of some biofilm-associated metals declined following sequential treatment, for example copper (73% reduction), zinc (48% reduction) and lead (46% reduction). In contrast, levels of arsenic, cadmium, chromium and nickel were not reduced by the treatment system. We demonstrate that biofilm bacterial community composition is a sensitive indicator of environmental changes within freshwater ecosystems and an efficient indicator to monitor water quality in enclosed stormwater networks where traditional biological indicators are not available. PMID- 24210359 TI - Increased nitrous oxide accumulation by bioelectrochemical denitrification under autotrophic conditions: kinetics and expression of denitrification pathway genes. AB - Under autotrophic conditions, we investigated the effects of different current densities on bioelectrochemical denitrification (BED). In this study, nitrate consumption and nitrous oxide (N2O) production, microbial diversity and population dynamics, and denitrification pathway gene expressions were explored in continuous flow BED reactors at different current densities (0.2, 1, 5, 10 and 20 A/m(2)). We found that, under the autotrophic conditions, N2O accumulation was increased with increase in current density. The maximum rate of denitrification was 1.65 NO3(-)-N (g/NCCm(3).h), and approximately 70% of the reduced N was accumulated as N2O. After each current density was applied, pyrosequencing of the expressed 16S rRNA genes amplified from the cathodic biofilms revealed that that 16 genera were active and in common at all currents, and that eight of those showed a statistically significant correlation with particular current densities. The relative expression of napA and narG was highest, whereas nosZ was low relative to its level in the inoculum suggesting that this could have contributed the high N2O accumulation. Kinetic analysis of nitrate reduction and N2O accumulation followed Michaelis-Menten kinetics. The Vmax for nitrate consumption and N2O accumulation were similar, however the Km values determined as A/m(2) were not. This study provides better understanding of the community and kinetics of a current-fed, autotrophic, cathodic biofilm for evaluating its potential for scale-up and for N2O recovery. PMID- 24210361 TI - The impact of assessment and reassessment documentation on the trajectory of postoperative pain severity: a pilot study. AB - Comparing organizational approaches to pain management is warranted to understand best practices and provide decision makers with evidence on which to base resource intensive documentation policy decisions. To provide this evidence, a multilevel modeling (MLM) approach is required to accommodate the interrelatedness and nested nature of pain management factors affecting outcomes. Along with MLM, the widespread adoption of the electronic record provides an ability to capitalize on the repeated measurement benefit of the current pain management documentation output by using pain severity trajectory (PST) as a precise and clinically relevant outcome of interest. Therefore, the purpose of this pilot study was to examine the methodological issues that arise when conducting MLM research aimed to answer the question: what is the impact of assessment and reassessment documentation routines on postoperative pain severity trajectory? Researchers used timed pain management documentation data output to construct a growth model of a patient's PST and performed a two-level analysis from a convenience sample of 3 hospitals and 146 patients. Analyses revealed that the hospital where care occurred, the type of surgical procedure, and the presence of reassessment documentation within one hour of intervention affected the PST. Pilot work showed that pain management documentation output could be reformulated into research variables for hypothesis testing. The presentation of the reassessment data output posed a measurement limitation. An interdisciplinary research team is needed to adequately compare organizational practices. Basing policies on evidence has the potential to improve pain management care. PMID- 24210360 TI - Prevalence of synchronous second primary malignancy: identification using whole body PET/CT imaging. AB - OBJECTIVE: To describe the prevalence of synchronous second primary malignancy detected by PET/ CT in our clinical practice and its differentiating features from metastatic lesion. METHODS: All PET/CT scans from 1st October 2009 to 30th September 2010 were reviewed. The suspected cases of synchronous second primary malignancy detected by PET/CT were selected, and the histologically confirmed ones were being illustrated. Metachronous second primary cases were excluded. RESULTS: A total of 1522 scans were reviewed. sixty-eight cases were suspected to have a synchronous second primary while 8 were histologically confirmed. Seven (0.4%) of them were malignant and 1 was a benign tumor. These 7 cases were illustrated, and we found a significant difference in SUV(max) values and site of occurrence unusual to metastasis that were the two main radiological features differentiating them from metastatic lesion. CONCLUSION: Synchronous second primary malignancy could be missed without the use of whole body imaging. Its diagnosis is of utmost importance to prevent erroneous upstaging of disease and subsequent palliative treatment instead of curative surgery. PMID- 24210362 TI - The dynamic process of adherence to a renal therapeutic regimen: perspectives of patients undergoing continuous ambulatory peritoneal dialysis. AB - BACKGROUND: The nature of end-stage renal disease and the need for continuous ambulatory peritoneal dialysis require patients to manage various aspects of the disease, its symptoms and treatment. After attending a training programme, patients are expected to adhere to the renal therapeutic regimen and manage their disease with the knowledge and skills learned. While patients are the stakeholders of their health and related behaviour, their perceptions of adherence and how they adhere to their renal therapeutic regimen remains unexplored. AIMS: To understand adherence from patients' perspectives and to describe changes in adherence to a therapeutic regimen among patients undergoing continuous ambulatory peritoneal dialysis. DESIGN: This study used a mixed methods design with two phases - a survey in phase I and semi-structured interviews in phase II. This paper presents phase II of the study. SETTINGS: The study was conducted at a renal unit of an acute hospital in Hong Kong. PARTICIPANTS: Based on the phase I survey results, maximum variation sampling was employed to purposively recruit 36 participants of different genders (18 males, 18 females), ages (35-76 years), and lengths of dialysis experience (11-103 months) for the phase II interviews. METHODS: Data were collected by tape recorded semi-structured interviews. Content analysis was employed to analyse the transcribed data. Data collection and analysis were conducted simultaneously. FINDINGS: Adherence was a dynamic process with three stages. At the stage of initial adherence, participants attempted to follow instructions but found that strict persistent adherence was impossible. After the first 2-6 months of dialysis, participants entered the stage of subsequent adherence, when they adopted selective adherence through experimenting, monitoring and making continuous adjustments. The stage of long-term adherence commenced after 3-5 years of dialysis, when participants were able to assimilate the modified therapeutic regimen into everyday life. CONCLUSIONS: The process of adherence was dynamic as there were fluctuations at each stage of the participants' adherence. With reference to each stage identified, nursing interventions can be developed to help patients achieve smooth transition throughout all the stages. PMID- 24210363 TI - Environmental circumstances influencing tic expression in children. AB - AIM: To assess the clinical features and severity of tics and environmental factors influencing tic expression in a cohort of children with tic disorders. METHODS: We performed a cross-sectional study in a cohort of children and adolescents (N = 92) with tic disorders referred to the outpatient clinic of a tertiary-level paediatric centre in Barcelona. The severity of tics was evaluated using the Yale Global Tic Severity Scale (YGTSS). A questionnaire including a list of environmental factors and common daily activities that might influence tic occurrence was completed for patients greater than 5 years old. RESULTS: Children were classified as having Tourette syndrome (TS) (52 patients), chronic motor or phonic tics (22 patients) and tics of less than 12 months' duration (18 patients). Tics worsened with stressful situations, activities related to school, playing video games and watching TV. A significant proportion of children reported a reduction in tics while they were concentrating on artistic or creative activities or when playing sports and participating in outdoor activities. The YGTSS scores were higher for TS patients (P < .001) and correlated positively with the time of evolution of tics (r = .273, P = .026). Poor school performance was associated with TS (p = .043) and higher scores on the YGTSS (P = .018), as well as attention deficit/hyperactivity disorder (P = .007). CONCLUSIONS: Several activities of daily living were identified as modifying tic severity in children and may be important clues for tic management. In a subgroup of children with TS, tics were associated with significant morbidity and poor academic performance. Our results emphasise the importance of developing specific school programmes and tailored recommendations in patients with TS. PMID- 24210364 TI - A brief overview of the potential environmental hazards of ionic liquids. AB - Over past decades ionic liquids, a promising alternative to traditional organic solvents, have been dramatically expanding in popularity as a new generation of chemicals with potential uses in various areas in industry. In the literature these compounds have often been referred to as environmentally friendly; however, in recent years the perception of their greenness dramatically changed as the scientific community began to proactively assess the risk of their application based on the entire life-cycle. This review gives a brief overview of the current knowledge regarding the potential risks linked to the application of ionic liquids - from preparation to their disposal, with special emphasis on their potential environmental impacts and future directions in designing inherently safer ionic liquids. PMID- 24210365 TI - Arsenic accumulation by edible aquatic macrophytes. AB - Edible aquatic macrophytes grown in arsenic (As)-contaminated soil and sediment were investigated to determine the extent of As accumulation and potential risk to humans when consumed. Nasturtium officinale (watercress) and Diplazium esculentum (warabi) are two aquatic macrophytes grown and consumed in Hawaii. Neither has been assessed for potential to accumulate As when grown in As contaminated soil. Some former sugarcane plantation soils in eastern Hawaii have been shown to have concentrations of total As over 500 mg kg(-1). It was hypothesized that both species will accumulate more As in contaminated soils than in non-contaminated soils. N. officinale and D. esculentum were collected in areas with and without As-contaminated soil and sediment. High soil As concentrations averaged 356 mg kg(-1), while low soil As concentrations were 0.75 mg kg(-1). Average N. officinale and D. esculentum total As concentrations were 0.572 mg kg(-1) and 0.075 mg kg(-1), respectively, corresponding to hazard indices of 0.12 and 0.03 for adults. Unlike previous studies where watercress was grown in As-contaminated water, N. officinale did not show properties of a hyperaccumulator, yet plant concentrations in high As areas were more than double those in low As areas. There was a slight correlation between high total As in sediment and soil and total As concentrations in watercress leaves and stems, resulting in a plant uptake factor of 0.010, an order of magnitude higher than previous studies. D. esculentum did not show signs of accumulating As in the edible fiddleheads. Hawaii is unique in having volcanic ash soils with extremely high sorption characteristics of As and P that limit release into groundwater. This study presents a case where soils and sediments were significantly enriched in total As concentration, but the water As concentration was below detection limits. PMID- 24210366 TI - Donation after circulatory determination of death: time for transparency. PMID- 24210367 TI - Does initial hydromorphone relieve pain best if dosing is fixed or weight based? AB - STUDY OBJECTIVE: It remains unknown whether initial opioid dosing should optimally be fixed or weight-based. We wish to determine whether pain response after an initial fixed dose of intravenous hydromorphone varied by total body weight. METHODS: We enrolled a convenience sample of emergency department adults aged 18 to 65 years with acute pain requiring intravenous opioids and administered 1 mg of hydromorphone. Our primary outcome was the correlation of total body weight with the reduction in pain at 30 minutes, as measured with a numeric rating scale. Our secondary outcomes contrasted total body weight by other measures of efficacy (numeric rating scale <3, pain relief, satisfaction, and desire for more analgesics) and adverse events (nausea, vomiting, and pruritus). We also performed a multivariate analysis to control for variables that might affect the relationship of pain response to total body weight. RESULTS: We enrolled 163 subjects with a range of weights from 45 to 157 kg, and their mean numeric rating scale pain reduction at 30 minutes was 5.3. Pain reduction did not correlate with weight in either univariate or multivariable models. Secondary outcomes were also similar, except greater pruritus in lower weight subjects. CONCLUSION: Pain response to a fixed 1 mg intravenous dose of hydromorphone did not vary by total body weight in this sample of adults aged 18 to 65 years, suggesting no advantage to weight-based over fixed opioid dosing. PMID- 24210368 TI - Topical lidocaine to improve oral intake in children with painful infectious mouth ulcers: a blinded, randomized, placebo-controlled trial. AB - STUDY OBJECTIVE: We establish the efficacy of 2% viscous lidocaine in increasing oral intake in children with painful infectious mouth conditions compared with placebo. METHODS: This was a randomized placebo-controlled trial of viscous lidocaine versus placebo at a single pediatric emergency department. Study staff, clinicians, nurses, caregivers, and participants were blinded to the group assignment. Children with acute infectious ulcerative mouth conditions (gingivostomatitis, ulcerative pharyngitis, or hand, foot, and mouth disease) and poor oral fluid intake were randomized to receive 0.15 mL/kg of either 2% viscous lidocaine or placebo with identical appearance and flavor. The primary outcome was the amount of fluid ingested in the 60 minutes after administration of the intervention, with a difference in intake of 4 mL/kg considered clinically important. Secondary outcomes were specific milliliter per kilogram fluid targets and incidence of adverse events. RESULTS: One hundred participants were recruited (50 per treatment group), all of whom completed the 60-minute fluid trial period. Oral intake 1 hour after drug administration was similar in both groups: lidocaine median 8.49 mL/kg (interquartile range 4.07, 13.84 mL/kg) versus placebo 9.31 mL/kg (interquartile range 3.06, 15.18 mL/kg); difference in medians 0.82 mL/kg (95% confidence interval -2.52 to 3.26); Mann-Whitney P=.90. Likewise, short-term secondary outcomes were similar between the groups and there were no adverse events in either group. CONCLUSION: Viscous lidocaine is not superior to a flavored gel placebo in improving oral intake in children with painful infectious mouth ulcers. PMID- 24210369 TI - Primary percutaneous coronary intervention for refractory cardiac arrest. AB - The identification and treatment of reversible causes is paramount to the success of resuscitation in cardiac arrest, particularly when standard therapy has failed. Acute coronary occlusion is one such cause, and the introduction of primary percutaneous coronary intervention services may provide an opportunity for emergency revascularization in this setting. This article describes 2 patients with cardiac arrest as a result of coronary occlusion, in which standard therapeutic measures proved futile. The first patient had refractory ventricular fibrillation, and the second had an episode of ventricular fibrillation followed by true pulseless electrical activity: total cessation of ventricular activity. In both examples, external mechanical compression and primary percutaneous coronary intervention facilitated coronary revascularization and achieved return of spontaneous circulation, leading to survival to hospital discharge. PMID- 24210370 TI - Cutaneous squamous cell carcinomas of the lower extremity: a distinct subset of squamous cell carcinomas. AB - BACKGROUND: Some patients develop a disproportionate number of cutaneous squamous cell carcinomas (SCCs) on their lower extremity (LE). OBJECTIVE: We sought to characterize the clinical features, treatment, and outcome in patients who develop multiple LE SCCs. METHODS: We identified 22 patients with 4 or more biopsy-diagnosed LE SCCs during a 4.5-year study period. The location, size, treatment, and clinical outcome of each LE SCC were recorded. RESULTS: Of the 22 patients studied, 18 were female. Of the 360 SCCs our patients developed, 260 (72.2%) were on the LE. The incidence of SCCs in these patients was nearly 7 times greater than the incidence of basal cell carcinoma in the same patients. LIMITATIONS: The number of patients is small and limits definitive conclusions about prevalence of SCCs on the LE in the general population. CONCLUSIONS: LE SCCs are a distinct subset of cutaneous SCCs and may have distinctive clinical features and biologic behavior requiring additional study. PMID- 24210371 TI - Synthesis, photostability and bioactivity of 2,3-cyclopropanated abscisic acid. AB - The plant hormone abscisic acid (ABA) plays a central role in the regulation of plant development and adaptation to environmental stress. The isomerization of ABA to the biologically inactive 2E-isomer by light considerably limits its applications in agricultural fields. To overcome this shortcoming, an ABA analogue, cis-2,3-cyclopropanated ABA, was synthesized, and its photostability and biological activities were investigated. This compound showed high photostability under UV light exposure, which was 4-fold higher than that of (+/ )-ABA. cis-2,3-cyclopropanated ABA exhibited high ABA-like activity, including the ability to effectively inhibit seed germination, seedling growth and stomatal movements of Arabidopsis. In some cases, its bioactivity approaches that of (+/-) ABA. trans-2,3-cyclopropanated abscisic acid was also prepared, an isomer that was more photostable but which showed weak ABA-like activity. PMID- 24210372 TI - Anti-HIV active daphnane diterpenoids from Trigonostemon thyrsoideum. AB - Sixteen daphnane diterpenoids, trigothysoids A-P, along with 15 known ones, were isolated from the methanol extract of the twigs and leaves of Trigonostemon thyrsoideum. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The anti-HIV-1 activity of the compounds was also evaluated in vitro, and five compounds demonstrated potent anti-HIV-1 activity, with EC50 values of 0.015-0.001 nM and TI values of 1618-17,619. PMID- 24210373 TI - Influence of lake trophic structure on iodine-131 accumulation and subsequent cumulative radiation dose to trout thyroids. AB - Iodine-131 is a major component of the atmospheric releases following reactor accidents, and the passage of (131)I through food chains from grass to human thyroids has been extensively studied. By comparison, the fate and effects of (131)I deposition onto lakes and other aquatic systems have been less studied. In this study we: (1) reanalyze 1960s data from experimental releases of (131)I into two small lakes; (2) compare the effects of differences in lake trophic structures on the accumulation of (131)I by fish; (3) relate concentrations in fish and fish tissues to that in the water column using empirically estimated uptake (L kg(-1) d(-1)) and loss (d(-1)) parameters; and (4) show that the largest concentrations in the thyroids of trout (Oncorhynchus mykiss) may occur from 8 to 32 days after initial release. Iodine-131 concentration in trout thyroids at 30-days post release may be >1000 times that in the water. Estimates of cumulative radiation dose (mGy) to thyroids computed using an anatomically appropriate model of trout thyroid structure within the Monte Carlo N-particle modeling software predicted cumulative thyroid doses that increased approximately linearly after the first 8 days and resulted in 32-day cumulative thyroid doses that ranged from 6 mGy g(-1) to 18 mGy g(-1) per 1 Bq mL(-1) of initial (131)I in the water depending upon fish size. The majority of this dose is due to beta emissions, and the dose varies with positions in the thyroid tissue. PMID- 24210413 TI - Interaction of low-frequency axisymmetric ultrasonic guided waves with bends in pipes of arbitrary bend angle and general bend radius. AB - The use of ultrasonic guided waves for the inspection of pipes with elbow and U type bends has received much attention in recent years, but studies for more general bend angles which may also occur commonly, for example in cross-country pipes, are limited. Here, we address this topic considering a general bend angle phi, a more general mean bend radius R in terms of the wavelength of the mode studied and pipe thickness b. We use 3D Finite Element (FE) simulation to understand the propagation of fundamental axisymmetric L(0,2) mode across bends of different angles phi. The effect of the ratio of the mean bend radius to the wavelength of the mode studied, on the transmission and reflection of incident wave is also considered. The studies show that as the bend angle is reduced, a progressively larger extent of mode-conversion affects the transmission and velocity characteristics of the L(0,2) mode. However the overall message on the potential of guided waves for inspection and monitoring of bent pipes remains positive, as bends seem to impact mode transmission only to the extent of 20% even at low bend angles. The conclusions seem to be valid for different typical pipe thicknesses b and bend radii. The modeling approach is validated by experiments and discussed in light of physics of guided waves. PMID- 24210414 TI - Nondestructive evaluation of helicopter rotor blades using guided Lamb modes. AB - This paper presents an application for turning and direct modes in a complex composite laminate structure. The propagation and interaction of turning modes and fundamental Lamb modes are investigated in the skin, spar and web sections of a helicopter rotor blade. Finite element models were used to understand the various mode conversions at geometric discontinuities such as web-spar joints. Experimental investigation was carried out with the help of air coupled ultrasonic transducers. The turning and direct modes were confirmed with the help of particle displacements and velocities. Experimental B-Scans were performed on damaged and undamaged samples for qualitative and quantitative assessment of the structure. A strong correlation between the numerical and experimental results was observed and reported. PMID- 24210415 TI - Dynamic ultrasonic contact detection using acoustic emissions. AB - For a non-contact ultrasonic material removal process, the control of the standoff position can be crucial to process performance; particularly where the requirement is for a standoff of the order of <20 MUm. The standoff distance relative to the surface to be machined can be set by first contacting the ultrasonic tool tip with the surface and then withdrawing the tool to the required position. Determination of this contact point in a dynamic system at ultrasonic frequencies (>20 kHz) is achieved by force measurement or by detection of acoustic emissions (AE). However, where detection of distance from a surface must be determined without contact taking place, an alternative method must be sought. In this paper, the effect of distance from contact of an ultrasonic tool is measured by detection of AE through the workpiece. At the point of contact, the amplitude of the signal at the fundamental frequency increases significantly, but the strength of the 2nd and 3rd harmonic signals increases more markedly. Closer examination of these harmonics shows that an increase in their intensities can be observed in the 10 MUm prior to contact, providing a mechanism to detect near contact (<10 MUm) without the need to first contact the surface in order to set a standoff. PMID- 24210416 TI - Preoperative fasting: sugary drinks for women behind 'two in the queue' for caesarean section. PMID- 24210417 TI - The 2013 Gerard W. Ostheimer Lecture: What's New in Obstetric Anesthesia? AB - The "What's New in Obstetric Anesthesia?" lecture is delivered annually in honor of the eminent obstetric anesthesiologist Gerard. W. Ostheimer. This lecture summarizes topics of importance and clinical relevance published in the fields of obstetric anesthesia, obstetrics, and perinatology in the preceding year. The review is a redacted version of the lecture delivered at the Society for Obstetric Anesthesia and Perinatology's Annual Meeting in April 2013. Special emphasis is placed on non-invasive technologies and biomarkers that have the potential to improve clinical care of the pregnant woman. Furthermore, sufficient attention is focused on medical diseases that have their onset or are worsened during pregnancy. PMID- 24210418 TI - Initial experience of percutaneous coronary intervention in bifurcations with bioresorbable vascular scaffolds using different techniques--insights from optical coherence tomography. PMID- 24210419 TI - Trends in abdominal aortic aneurysm prevalence and mortality in non-European countries. PMID- 24210420 TI - Patterns of cardiac dysfunction coinciding with exertional breathlessness in hypertrophic cardiomyopathy. AB - OBJECTIVE: The commonest cause of breathlessness in hypertrophic cardiomyopathy (HCM) is left ventricular outflow tract (LVOT) obstruction which improves with its removal. However, in the absence of outflow tract obstruction, as in dilated cardiomyopathy, patients may be limited by similar symptoms, thus suggesting a potential common mechanism for the two conditions. We aimed to assess cardiac function at the time of symptoms in a group of unselected patients with HCM to identify other patterns of cardiac dysfunction which coincide with their breathlessness. METHODS: We studied 37 HCM patients (aged 55 +/- 15 years, 13 female) with septal thickness >15 mm and 17 controls (aged 58 +/- 12 years, 12 female) using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms, >20 mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine dosage of 40 MUg/kg/min. RESULTS: At rest: LV systolic function was maintained (EF 68 +/- 7 v 76 +/- 12%, respectively), LVOT velocity raised (p<0.005), lateral and septal long axis amplitude reduced (p<0.05 and p<0.005, respectively) and dyssynchronous and QRS duration was also broader (p<0.005) in patients compared to controls. At peak stress: Overall LVOT velocities were higher in patients than controls (4.3 +/- 1.7 v 1.7 +/- 1.0m/s, p<0.005, respectively) due to systolic anterior movement of the mitral valve and mitral regurgitation developing. In the 15 patients who did not develop significant LVOT obstruction (velocity <4m/s), LV ejection time increased and peak systolic amplitude did not increase. In the 10 patients with neither LVOT obstruction nor restrictive filling, QRS duration prolonged by 12 ms (p <0.05), post-ejection shortening worsened and peak systolic amplitude fell (p<0.005). Also, LV ejection time prolonged by 5s/min (p<0.05), filling time failed to increase as it did in controls (p<0.005) and Tei index was higher than controls (p<0.01). CONCLUSION: Exertional breathlessness in HCM is associated with LV outflow tract obstruction and functional mitral regurgitation in almost two thirds of patients. The remaining one third have either resistant restrictive physiology or dyssynchronous cavity at fast heart rate. Despite similar exercise limiting breathlessness in the three groups, means of management should be quite different. PMID- 24210421 TI - Heart rate control in chronic heart failure: resting versus mean heart rate with prolonged ambulatory ECG recording. PMID- 24210422 TI - Discrepancies in prevalence estimates in two national surveys for nonmedical use of a specific opioid product versus any prescription pain reliever. AB - BACKGROUND: There is a growing need to understand trends in nonmedical use of prescription pain relievers as a class, as well as specific opioid products. Surveys such as monitoring the future (MTF) and the National Survey on Drug Use and Health (NSDUH) are important tools for understanding trends in abuse of prescription and illegal drugs. This report compares discrepancies in prevalence between these surveys for a specific opioid product (oxycodone) relative to other drugs. METHODS: Trends in past-year use of marijuana, cocaine, and nonmedical use of oxycodone and any prescription pain reliever were estimated for each survey for a five year period (2005-2010) for adolescents in 12th grade. The proportion of nonmedical pain reliever users who abused oxycodone was estimated for each survey. RESULTS: Prevalence of past-year oxycodone nonmedical use was steady over time for both surveys, but 2.5-3 times higher in the MTF compared to the NSDUH. Trends in prevalence of marijuana and cocaine use were similar across surveys, although prevalence estimates for each were on average 18% higher in the MTF. In contrast, prevalence estimates for any nonmedical prescription pain reliever use were on average 15% lower in MTF. The proportion of nonmedical prescription pain reliever users who used oxycodone was 42% in the MTF versus 19% in the NSDUH. CONCLUSION: The discrepancy between surveys in prevalence estimates for nonmedical use of oxycodone exceed those for other drugs, pointing to the importance of visual aids and items used to measure the nonmedical use of specific products. PMID- 24210424 TI - Association between depression and non-fatal overdoses among drug users: a systematic review and meta-analysis. AB - BACKGROUND: Assessing factors associated with non-fatal overdose is important as these could be useful to identify individuals with substance use disorders at high risk of adverse outcomes and consequences. Depression may play an important role in terms of overdose risk. We aimed to test if drug users suffering from a depressive disorder might have significantly higher risk of non-fatal overdose as compared with drug users without depression. METHODS: We conducted a systematic review and meta-analysis. PubMed, Embase and Web of Knowledge were searched. The pooled analyses were based on prevalence rates, risk difference (RD) and odds ratio (OR), reporting 95% confidence intervals (CIs). The combined estimates were obtained weighting each study according to random effects model for meta analysis. RESULTS: Seven articles, involving 12,019 individuals, and run in the US, Canada, Sweden, Norway, and Australia, were included. Pooled analyses comparing depressed with not depressed individuals highlighted a RD (95% CIs) for non-fatal overdose of 7.3% (4.8-9.7%) and an OR (95% CIs) of 1.45 (1.17-1.79). The subgroups analyses based on specific characteristics of included studies confirmed the association between depression and overdose. CONCLUSIONS: Depressive disorders seem to be important factors associated to the risk of non fatal overdose. Longitudinal studies might appropriately clarify causal inference issues. Future research should address the role of depressive disorders as predictors of subsequent non-fatal overdoses. PMID- 24210423 TI - Default mode network activity in male adolescents with conduct and substance use disorder. AB - BACKGROUND: Adolescents with conduct disorder (CD) and substance use disorders (SUD) experience difficulty evaluating and regulating their behavior in anticipation of future consequences. Given the role of the brain's default mode network (DMN) in self-reflection and future thought, this study investigates whether DMN is altered in adolescents with CD and SUD, relative to controls. METHODS: Twenty adolescent males with CD and SUD and 20 male controls of similar ages underwent functional magnetic resonance imaging as they completed a risk taking decision task. We used independent component analysis as a data-driven approach to identify the DMN spatial component in individual subjects. DMN activity was then compared between groups. RESULTS: Compared to controls, patients showed reduced activity in superior, medial and middle frontal gyrus (Brodmann area (BA) 10), retrosplenial cortex (BA 30) and lingual gyrus (BA 18), and bilateral middle temporal gryus (BA 21/22) - DMN regions thought to support self-referential evaluation, memory, foresight, and perspective taking. Furthermore, this pattern of reduced activity in patients remained robust after adjusting for the effects of depression and attention-deficit hyperactivity disorder (ADHD). Conversely, when not adjusting for effects of depression and ADHD, patients demonstrated greater DMN activity than controls solely in the cuneus (BA 19). CONCLUSIONS: Collectively, these results suggest that comorbid CD and SUD in adolescents is characterized by atypical activity in brain regions thought to play an important role in introspective processing. These functional imbalances in brain networks may provide further insight into the neural underpinnings of conduct and substance use disorders. PMID- 24210425 TI - Can a redesign of emergency pharmacist roles improve medication management? A prospective study in three Australian hospitals. AB - BACKGROUND: Emergency departments (EDs) face increasing service demands and the imposition of treatment targets which has led to continual process redesign and changes in staff skill mix and functions. OBJECTIVE: To identify extended ED pharmacist roles that could improve medication management and to implement and evaluate one such role change. METHODS: A focus group of clinicians sought to redesign processes around ED medication management. Preparation of medication charts for patients admitted from ED was selected. Baseline data were obtained to define elements of existing medication charting processes. Suitably trained ED pharmacists' trialled the effectiveness of making therapeutic suggestions on a medication chart 'sticker' or by direct 'consultation' with medical staff. At the conclusion of the study focus groups at each site evaluated clinical staff perceptions of the change. RESULTS: Focus group participants thought that ED pharmacists could undertake extended roles in analgesia, nausea control, antibiotic cover, addiction management and preparation of medication charts for admitted patients. In the pre-intervention audit (n = 140), 74% required at least one intervention by the ward pharmacists to address medication discrepancies. Ward pharmacists detected 292 medication discrepancies (median 1, IQR 0-3). In the 'sticker' intervention the ED pharmacist made 84 therapeutic suggestions of which 66 (78.6%) were accepted by medical staff. In the 'consultation' intervention 230 therapeutic suggestions were made of which 219 (95.2%) were accepted. The qualitative evaluation found that pharmacist-prepared medication charts within the processes established were deemed safe, timely, accurate, complete and legible. CONCLUSION: Support exists for ED pharmacists to expand their medication-related roles. ED pharmacists can safely prepare medication charts in a timely fashion and their therapeutic suggestions within a 'consultative' framework are more beneficial than written advice. However, issues relating to resourcing, hours of service, service focus, statutory restrictions and training support for extended roles require resolution. PMID- 24210426 TI - Spectrin- and ankyrin-based membrane domains and the evolution of vertebrates. AB - Spectrin and ankyrin are membrane skeletal proteins that contribute to mechanical support of plasma membranes and micron-scale organization of diverse membrane spanning proteins. This chapter provides a plausible scenario for the evolution of ankyrin- and spectrin-based membrane domains with a focus on vertebrates. The analysis integrates recent phylogenetic information with functional analyses of spectrin and ankyrin in erythrocytes, axon initial segments and nodes of Ranvier in neurons, T-tubules and intercalated disks of cardiomyocytes, lateral membrane domains of epithelial cells, and costameres of striated muscle. A core spectrin ankyrin mechanism for coordinating membrane-spanning proteins and mechanically stabilizing membrane bilayers was expanded in vertebrates by gene duplication events, insertion of giant alternately spliced exons of axonal ankyrins, and a versatile peptide-binding fold of ANK repeats that facilitated acquisition of new protein partners. Cell adhesion molecules (CAM), including dystroglycan, L1 CAM family members, and cadherins, are the earliest examples of membrane-spanning proteins with ankyrin-binding motifs and were all present in urochordates. In contrast, ion channels have continued to evolve ankyrin-binding sites in vertebrates. These considerations suggest a model where proto-domains formed through interaction of ankyrin and spectrin with CAMs. These proto-domains then became populated with ion channels that developed ankyrin-binding activity with selective pressure provided by optimization of physiological function. The best example is the axon initial segment where ankyrin-binding activity evolved sequentially and independently first in L1 CAMs, then in voltage-gated sodium channels, and finally in KCNQ2/3 channels, with the selective advantage of fast and precisely regulated signaling. PMID- 24210427 TI - The human erythrocyte plasma membrane: a Rosetta Stone for decoding membrane cytoskeleton structure. AB - The mammalian erythrocyte, or red blood cell (RBC), is a unique experiment of nature: a cell with no intracellular organelles, nucleus or transcellular cytoskeleton, and a plasma membrane with uniform structure across its entire surface. By virtue of these specialized properties, the RBC membrane has provided a template for discovery of the fundamental actin filament network machine of the membrane skeleton, now known to confer mechanical resilience, anchor membrane proteins, and organize membrane domains in all cells. This chapter provides a historical perspective and critical analysis of the biochemistry, structure, and physiological functions of this actin filament network in RBCs. The core units of this network are nodes of ~35-37 nm-long actin filaments, interconnected by long strands of (alpha1beta1)2-spectrin tetramers, forming a 2D isotropic lattice with quasi-hexagonal symmetry. Actin filament length and stability is critical for network formation, relying upon filament capping at both ends: tropomodulin-1 at pointed ends and alphabeta-adducin at barbed ends. Tropomodulin-1 capping is essential for precise filament lengths, and is enhanced by tropomyosin, which binds along the short actin filaments. alphabeta-adducin capping recruits spectrins to sites near barbed ends, promoting network formation. Accessory proteins, 4.1R and dematin, also promote spectrin binding to actin and, with alphabeta-adducin, link to membrane proteins, targeting actin nodes to the membrane. Dissection of the molecular organization within the RBC membrane skeleton is one of the paramount achievements of cell biological research in the past century. Future studies will reveal the structure and dynamics of actin filament capping, mechanisms of precise length regulation, and spectrin-actin lattice symmetry. PMID- 24210429 TI - Evolving form to fit function: cardiomyocyte intercalated disc and transverse tubule membranes. AB - The vertebrate cardiac myocyte has evolved a highly organized cellular membrane architecture and cell-cell contacts in order to effectively transmit precisely timed and homogeneous depolarizing waves without failure (>2 billion times/human life span). Two unique specialized membrane domains, the intercalated disc and the transverse tubule (T-tubule), function to ensure the rapid and coordinated propagation of the action potential throughout the heart. Based on their critical roles in structure, signaling, and electric inter- and intracellular communication, it is not surprising that dysfunction in these membrane structures is associated with aberrant vertebrate physiology, resulting in potentially fatal congenital and acquired disease. This chapter will review the fundamental components of cardiomyocyte intercalated disc and transverse-tubule membranes with a focus on linking dysfunction in these membranes with human cardiovascular disease. PMID- 24210428 TI - Membrane protein dynamics and functional implications in mammalian cells. AB - The organization of the plasma membrane is both highly complex and highly dynamic. One manifestation of this dynamic complexity is the lateral mobility of proteins within the plane of the membrane, which is often an important determinant of intermolecular protein-binding interactions, downstream signal transduction, and local membrane mechanics. The mode of membrane protein mobility can range from random Brownian motion to immobility and from confined or restricted motion to actively directed motion. Several methods can be used to distinguish among the various modes of protein mobility, including fluorescence recovery after photobleaching, single-particle tracking, fluorescence correlation spectroscopy, and variations of these techniques. Here, we present both a brief overview of these methods and examples of their use to elucidate the dynamics of membrane proteins in mammalian cells-first in erythrocytes, then in erythroblasts and other cells in the hematopoietic lineage, and finally in non-hematopoietic cells. This multisystem analysis shows that the cytoskeleton frequently governs modes of membrane protein motion by stably anchoring the proteins through direct binding interactions, by restricting protein diffusion through steric interactions, or by facilitating directed protein motion. Together, these studies have begun to delineate mechanisms by which membrane protein dynamics influence signaling sequelae and membrane mechanical properties, which, in turn, govern cell function. PMID- 24210430 TI - Excitable domains of myelinated nerves: axon initial segments and nodes of Ranvier. AB - Neurons are highly polarized cells. They can be subdivided into at least two structurally and functionally distinct domains: somatodendritic and axonal domains. The somatodendritic domain receives and integrates upstream input signals, and the axonal domain generates and relays outputs in the form of action potentials to the downstream target. Demand for quick response to the harsh surroundings prompted evolution to equip vertebrates' neurons with a remarkable glia-derived structure called myelin. Not only Insulating the axon, myelinating glia also rearrange the axonal components and elaborate functional subdomains along the axon. Proper functioning of all theses domains and subdomains is vital for a normal, efficient nervous system. PMID- 24210431 TI - Microdomains of SNARE proteins in the plasma membrane. AB - Exocytosis is catalyzed by the engagement of SNARE proteins embedded in the plasma membrane with complementary SNAREs in the membrane of trafficking vesicles undergoing exocytosis. In most cells studied so far, SNAREs are not randomly distributed across the plasma membrane but are clustered and segregated in discrete membrane domains of defined size, composition, and stability. SNARE clusters have been intensively studied for more than a decade. Different mechanisms have been proposed to be responsible for SNARE clustering such as partitioning into cholesterol-enriched lipid rafts, hydrophobic mismatch, posttranslational modifications of the SNAREs including phosphorylation and palmitoylation, electrostatic protein-protein and protein-lipid interactions, homotypic and heterotypic protein interactions, and anchoring to the cortical cytoskeleton. Although several of these proposed mechanisms are still controversially discussed, it is becoming apparent that independent physicochemical principles must cooperate in a synergistic manner to yield SNARE microdomains. Here, we discuss the architecture and function of SNARE domains. We also discuss the various factors influencing SNARE clustering, resulting in a model that we believe may be of general use to explain domain formation of proteins in the plasma membrane. PMID- 24210432 TI - Photoreceptor inner and outer segments. AB - Photoreceptors are exquisitely adapted to transform light stimuli into electrical signals that modulate neurotransmitter release. These cells are organized into several compartments including the unique outer segment (OS). Its whole function is to absorb light and transduce this signal into a change of membrane potential. Another compartment is the inner segment where much of metabolism and regulation of membrane potential takes place and that connects the OS and synapse. The synapse is the compartment where changes in membrane potentials are relayed to other neurons in the retina via release of neurotransmitter. The composition of the plasma membrane surrounding these compartments varies to accommodate their specific functions. In this chapter, we discuss the organization of the plasma membrane emphasizing the protein composition of each region as it relates to visual signaling. We also point out examples where mutations in these proteins cause visual impairment. PMID- 24210436 TI - [Advanced practice in nursing in the intensive care units of Spain]. PMID- 24210433 TI - The evolutionary origin of epithelial cell-cell adhesion mechanisms. AB - A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell cell adhesion proteins comprising the classical cadherin/beta-catenin/alpha catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and beta-catenin in metazoa. (3) The alpha-catenin binding domain in beta-catenin appears to be the favored mutation site for disrupting beta-catenin function in the CCC. (4) The ancestral function of the alpha/beta-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of alpha-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of alpha-catenin may have evolved for more complex regulation of the actin cytoskeleton. PMID- 24210434 TI - "Cell biology meets physiology: functional organization of vertebrate plasma membranes"--the immunological synapse. AB - The immunological synapse (IS) is an excellent example of cell-cell communication, where signals are exchanged between two cells, resulting in a well structured line of defense during adaptive immune response. This process has been the focus of several studies that aimed at understanding its formation and subsequent events and has led to the realization that it relies on a well orchestrated molecular program that only occurs when specific requirements are met. The development of more precise and controllable T cell activation systems has led to new insights including the role of mechanotransduction in the process of formation of the IS and T cell activation. Continuous advances in our understanding of the IS formation, particularly in the context of T cell activation and differentiation, as well the development of new T cell activation systems are being applied to the establishment and improvement of immune therapeutical approaches. PMID- 24210438 TI - Placental evaluation with magnetic resonance. AB - Because of the high maternal morbidity and mortality of undiagnosed placental abnormalities, there is a need for accurate antenatal diagnosis. Important placental features amenable to investigation with magnetic resonance (MR) imaging include variant placental location and morphology, and abnormal implantation or invasion of placenta into the myometrium. MR imaging features permit the diagnosis of abnormal placentation include placental lobulation with uterine contour deformity, interruption of the inner low signal-intensity myometrial layer, and placental heterogeneity resulting from dark intraplacental bands and abnormal vascularity. PMID- 24210437 TI - Magnetic resonance imaging of female urethral and periurethral disorders. AB - This article reviews the normal anatomy of the female urethra, magnetic resonance (MR) imaging techniques, and the role of MR imaging in the evaluation of diverse urethral and periurethral diseases. Salient MR imaging findings of common and uncommon cystic urethral lesions (urethral diverticulum, Skene cyst, and vaginal cysts), and masses (urethral carcinoma, leiomyoma, melanoma, fibroepithelial polyp, caruncle, and mucosal prolapse) are presented. The evolving role of dynamic MR in the evaluation of stress urinary incontinence is reviewed. PMID- 24210439 TI - Imaging of female infertility: a pictorial guide to the hysterosalpingography, ultrasonography, and magnetic resonance imaging findings of the congenital and acquired causes of female infertility. AB - Hysterosalpingography is the gold standard in assessing the patency of the fallopian tubes, which is among the most common causes of female factor infertility, making this technique the most frequent first-choice imaging modality in the assessment of female infertility. Ultrasonography and magnetic resonance imaging are typically used for evaluation of indeterminate or complicated cases of female infertility and presurgical planning. Imaging also plays a role in the detection of the secondary causes of ovarian factor infertility, including endometriosis and polycystic ovarian syndrome. PMID- 24210440 TI - Obstetric (nonfetal) complications. AB - Pregnancy predisposes women to a wide array of obstetric and gynecological complications which are often complex, challenging and sometimes life threatening. While some of these are unique to pregnancy, a few that occur in nonpregnant women are more common during pregnancy. Imaging plays a crucial role in the diagnosis and management of pregnancy-related obstetric and gynecologic complications. Ultrasonography and magnetic resonance imaging confer the least risk to the fetus and should be the preferred examinations for evaluating these complications. Multidetector computed tomography should be used after carefully weighing the risk-benefit ratio based on the clinical condition in question. Interventional radiology is emerging as a preferred, noninvasive or minimally invasive treatment option that can obviate surgery and its antecedent short term and long term complications. Knowledge of appropriateness of imaging and image guided intervention is necessary for accurate patient management. PMID- 24210441 TI - Imaging of acute abdomen in pregnancy. AB - The approach to imaging in pregnancy is unique, as it is essential to minimize radiation exposure to the fetus. Ultrasonography and magnetic resonance imaging are the chief modalities for evaluation of the pregnant patient with abdominal pain. Use of computed tomography should not be delayed when there is a need for early diagnosis. This article discusses test selection and underlying reasoning, with a description of common imaging features of different causes of acute abdominal pain in pregnancy. Also discussed are current evidence-based recommendations for the use of iodinated and gadolinium-based contrast agents and the importance of patient counseling. PMID- 24210442 TI - Gestational trophoblastic disease. AB - Imaging plays a crucial role in diagnosis and management of gestational trophoblastic disease. Ultrasonography is the initial investigation of choice for the diagnosis. Pelvic magnetic resonance (MR) imaging is used as a problem solving tool for assessment of degree of local invasion. Chest radiography is the recommended initial radiographic staging modality, and chest computed tomography is performed if the radiograph is negative. (18)F-Fluorodeoxyglucose positron emission tomography has been shown to be useful in assessing the active or viable sites of metastases, thereby determining the need for tumor resectability in chemoresistant disease. PMID- 24210443 TI - Three-dimensional volumetric sonography in gynecology: an overview of clinical applications. AB - Three-dimensional (3D) sonography can significantly improve on the diagnostic ability of two-dimensional sonography of the pelvic organs. 3D sonography has become a problem-solving technique in the evaluation of a variety of gynecologic disorders involving the uterus, adnexa, and pelvic floor. It allows an accurate depiction of the uterine cavity and outline of the uterus in the coronal plane. 3D sonography is less expensive than other modalities, is convenient, and does not have the risk of radiation or potential nephrotoxicity from contrast that other imaging modalities have. It is a cost-effective tool to assess the pelvic organs. PMID- 24210444 TI - Role of interventional procedures in obstetrics/gynecology. AB - In uterine fibroid embolization (UFE), knowledge of the potential ovarian-uterine anastomoses is important because they provide collateral blood flow that may result in the failure of the UFE or ovarian nontarget embolization. Uterine artery embolization is an alternative treatment of postpartum hemorrhage with 80% to 90% bleeding control and in which fertility can be preserved. Diagnosis of pelvic congestion syndrome on routine sonographic or computed tomography/magnetic resonance imaging is often missed. Fallopian tube recanalization allows couples to have unlimited attempts to conceive naturally and avoids the risks (multiple pregnancies, ovarian hyperstimulation syndrome), and high cost of in vitro fertilization. PMID- 24210445 TI - Ovarian cystic lesions: a current approach to diagnosis and management. AB - The primary imaging modality for evaluation of ovarian cystic lesions is pelvic ultrasonography. Most ovarian cysts are benign and demonstrate typical sonographic features that support benignity. However, some ovarian cystic lesions have indeterminate imaging features, and the approach to management varies. This article discusses how to recognize and diagnose different types of ovarian cystic lesions, including an approach to management. The learning objective is to recognize imaging features of ovarian cystic lesions. PMID- 24210446 TI - Current concepts in the diagnosis and management of endometrial and cervical carcinomas. AB - Cross-sectional imaging modalities play a pivotal role in the diagnosis and multidisciplinary management of patients with endometrial and cervical carcinomas. Ultrasonography, including sonohysterography, permits evaluation of endometrial abnormalities and characterization of adnexal masses. Computed tomography, particularly in conjunction with (18)(F)-fluorodeoxyglucose positron emission tomography, is increasingly used to stage the cancers and to detect disease recurrence. Magnetic resonance imaging plays a major role in accurate locoregional staging of these cancers, and significantly influences treatment decisions and outcomes. This article discusses the role of imaging modalities in the diagnosis, management, and surveillance of these cancers. PMID- 24210447 TI - Positron emission tomography-computed tomography imaging for malignancies in women. AB - The role of Positron Emission Tomography/Computed Tomography (PET/CT) in the evaluation of various gynecologic malignancies in light of current available data is presented and illustrated with imaging examples, pearls, and common pitfalls. 18F-fluorodeoxyglucose PET/CT is being increasingly used in management of gynecologic malignancy and has useful applications in cervical, ovarian, and endometrial carcinoma. Sensitivity and specificity are superior compared with conventional imaging. However, there are limitations of which the reporting physician should be aware. This article introduces the available evidence and discusses the role of PET/CT in various gynecologic malignancies and highlights imaging pearls and potential pitfalls. PMID- 24210448 TI - Magnetic resonance imaging of pelvic floor dysfunction. AB - Pelvic floor dysfunction is largely a complex problem of multiparous and postmenopausal women and is associated with pelvic floor or organ descent. Physical examination can underestimate the extent of the dysfunction and misdiagnose the disorders. Functional magnetic resonance (MR) imaging is emerging as a promising tool to evaluate the dynamics of the pelvic floor and use for surgical triage and operative planning. This article reviews the anatomy and pathology of pelvic floor dysfunction, typical imaging findings, and the current role of functional MR imaging. PMID- 24210449 TI - The role of a modern radiologist in diagnosing female pelvic pathologies. PMID- 24210450 TI - Forensic psychiatry and the birth of the criminal insane asylum in modern Italy. AB - This paper focuses on the creation of the criminal insane asylum in Italy between unification in 1861 and World War I. The establishment of criminal insane asylums was a triumph of the positivist criminology of Cesare Lombroso, who advocated for an institution to intern insane criminals in his classic work, Criminal Man (1876). As a context for the analysis of the birth of the criminal insane asylum in Italy, this essay also outlines the history of the insanity plea in Italian criminal law and the young discipline of psychiatry during the fifty years after Italian unification. PMID- 24210451 TI - Assessing the quality of care for dying patients from the bereaved relatives' perspective: further validation of "Evaluating care and health outcomes--for the dying". AB - CONTEXT: Evaluating Care and Health Outcomes-for the Dying (ECHO-D) is a post bereavement questionnaire that assesses quality of care for the dying and is linked with the Liverpool Care Pathway for the Dying Patient (LCP). OBJECTIVES: To further assess the validity and reliability of the ECHO-D, namely the construct validity, internal consistency, and test-retest reliability of key composite scales. METHODS: Self-completion questionnaires were mailed to 778 next of-kin of consecutive deceased patients who had died an "expected" cancer death in a hospice or acute tertiary hospital. For those willing to complete ECHO-D for a second time, another copy was sent a month later. Maximum likelihood factor analysis and Cronbach's alpha test were conducted for four key composite scales. Test-retest reliability was assessed using percentage agreement, Kappa statistic, and Spearman's correlation coefficient (ordinal data). Comparisons between hospice and hospital groups were conducted using one-way between-groups analysis of variance. RESULTS: Following exclusions (n = 52), 255 of 726 next-of-kin agreed to participate (35.2% response rate). Maximum likelihood factor analysis showed a single factor for three of the scales, and all had good internal consistency (Cronbach's alpha >0.78). Barring two questions, all showed good or moderate stability over time. Overall, hospice participants reported the best quality of care, and hospital participants, where care was not supported by the LCP, reported the worst quality of care. CONCLUSION: These findings support ECHO D as a valid and reliable instrument to assess quality of care for the dying and assess the effectiveness of interventions such as the LCP. PMID- 24210452 TI - PCDDs, PCDFs, PCBs and OCPs in sediments from selected areas in the Slovak Republic. AB - Within our research project, 34 river bottom sediments were collected in 2006 2007 at five areas across Slovakia with industrial sources of persistent organic pollutants (Kosice, Krompachy, Nemecka, Sala, Novaky) and one background area (Starina). Sediments were analyzed for seven 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and 10 dibenzofurans (PCDFs), 12 dioxin-like and 6 indicator polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and 1,1,1, trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) with 1,1-dichloro-2,2-bis(p chlorophenyl)ethylene (p,p'-DDE). Analytical procedure based on accelerated solvent extraction followed by a semi-automated clean-up and fractionation was used. Determination of target compounds was performed by HRGC-HRMS analysis. Total WHO toxic equivalent WHO1998-PCDD/F/dl-PCB-TEQ concentrations ranged from 0.26 to 559 pg TEQ g(-1) dry matter (dm), with a median 2.2 pg TEQ g(-1) dm. The sums of six indicator PCBs were in the range 0.56-1014 ng g(-1) dm, with a median 11.8 ng g(-1) dm. The concentrations of organochlorine pesticides HCB and p,p' DDE/DDT varied from 0.15 to 34.8 ng g(-1) dm, with a median 0.91 ng g(-1) dm and 0.46-34.1 ng g(-1)dm, with a median 6.7 ng g(-1)dm, respectively. The most abundant congeners in all sediment samples among dioxins, furans and PCBs were OCDD, 1,2,3,4,6,7,8-HpCDF, PCB-118 and PCB-153. PMID- 24210453 TI - Efficacy and safety of a diode laser in second-stage implant surgery: a comparative study. AB - For more than a decade, peri-implant tissues have been treated with soft tissue lasers to create a bloodless flap for implant placement and to uncover implants with minimal bleeding, trauma, and anaesthesia. This study was designed to assess if dental implant uncovering is possible with a diode laser without anaesthesia, and to compare its performance with traditional cold scalpel surgery. Thirty patients with a total of 45 completely osseointegrated implants participated in this study. Patients were divided into two groups. For the study group, second stage implant surgery was done with a 970nm diode laser. For the control group, the implants were exposed with a surgical blade. Certain parameters were used for evaluation of the two techniques. The use of the diode laser obviated the need for local anaesthesia; there was a significant difference between the two groups regarding the need for anaesthesia (P<0.0001). However, there were no significant differences between the two techniques regarding duration of surgery, postoperative pain, time for healing, and success of the implants. The diode laser can be used effectively for second-stage implant surgery, providing both the dentist and the patient with additional advantages over the conventional methods used for implant exposure. PMID- 24210454 TI - Global proteomic characterization of uterine histotroph recovered from beef heifers yielding good quality and degenerate day 7 embryos. AB - The objective was to analyze the proteomic composition of uterine flushes collected from beef heifers on day 7 after insemination. Estrus was synchronized in crossbred beef heifers by using a protocol with a controlled intravaginal drug releasing device. Heifers detected in standing estrus (within 24-48 h after removal of controlled intravaginal drug releasing device) were inseminated (estrus = day 0) with frozen-thawed semen from a single ejaculate of a bull with proven fertility. Heifers from which an embryo was recovered (after slaughter on day 7) were classified as either having a viable embryo (morula/blastocyst stage) or a degenerate embryo (arrested at the 2- to 16-cell stage). The overall recovery rate (viable and degenerate combined) was 64%. Global liquid chromatography coupled to tandem mass spectrometry proteomic analysis of the histotroph collected identified 40 high-confidence proteins present on day 7; 26 proteins in the viable group, 10 in the degenerate group, and 4 shared between both groups. Five proteins (platelet-activating factor acetylhydrolase IB subunit gamma [PAFAH1B3], tubulin alpha-1D chain, tubulin beta-4A chain, cytochrome C, and dihydropyrimidinase-related protein-2) were unique or more abundant in the histotroph collected from animals with a viable embryo, and 1 protein (S100-A4) was more abundant in the histotroph collected from animals with a degenerate embryo. Of interest, PAFAH1B3, detected only in histotroph from the group yielding viable embryos, belongs to the group of platelet-activating factors that are known to be important for the development of the pre-implantation embryo in other species. To our knowledge this is the first report of PAFAH1B3 in relation to bovine early embryonic development. PMID- 24210455 TI - Hypothyroidism after radiotherapy of head and neck cancer. AB - AIM: Hypothyroidism is not commonly considered as a complication of radiotherapy to the head and neck region. The purpose of this retrospective study was to determine the frequency of thyroid dysfunction in patients after radiotherapy, to compare thyroid hormone levels in irradiated patients with Control group and to predict development of thyroid hypofunction in time. MATERIAL AND METHOD: Thyroid function was measured by means of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodthyronine (FT3) in 43 patients who had nonthyroid head-neck carcinomas treated by radiotherapy or radiotherapy in combination with other modalities. These data were compared with hormone levels of 40 Control group patients treated solely by surgery. RESULTS: Hypothyroidism was found in 35% of irradiated patients. In comparison with Control group there were significant differences between TSH and FT4 levels, difference between FT3 levels was insignificant. A correlation between hormone levels and follow-up was detected. CONCLUSION: Our results indicate that hypothyroidism is a frequent late side effect of radiotherapy to head and neck. Lifelong monitoring of thyroid function appears to be justified when radiotherapy is a part of treatment protocol. PMID- 24210456 TI - Using multivariate data reduction to predict postsurgery memory decline in patients with mesial temporal lobe epilepsy. AB - Predicting postsurgery memory decline is crucial to clinical decision-making for individuals with mesial temporal lobe epilepsy (mTLE) who are candidates for temporal lobe excisions. Extensive neuropsychological testing is critical to assess risk, but the numerous test scores it produces can make deriving a formal prediction of cognitive change quite complex. In order to benefit from the information contained in comprehensive memory assessment, we used principal component analysis (PCA) to simplify neuropsychological test scores (presurgical and pre- to postsurgical change) obtained from a cohort of 56 patients with mTLE into a few easily interpretable latent components. We next performed discriminant analyses using presurgery latent components to categorize seizure laterality and then regression analyses to assess how well presurgery latent components could predict postsurgery memory decline. Finally, we validated the predictive power of these regression models in an independent sample of 18 patients with mTLE. Principal component analysis identified three significant latent components that reflected IQ, verbal memory, and visuospatial memory, respectively. Together, the presurgery verbal and visuospatial memory components classified 80% of patients with mTLE correctly according to their seizure laterality. Furthermore, the presurgery verbal memory component predicted postsurgery verbal memory decline, while the presurgery visuospatial memory component predicted visuospatial memory decline. These regression models also predicted postsurgery memory decline successfully in the independent cohort of patients with mTLE. Our results demonstrate the value of data reduction techniques in identifying cognitive metrics that can characterize laterality of damage and risk of postoperative decline. PMID- 24210457 TI - Lesion side matters - an fMRI study on the association between neural correlates of watching dynamic fearful faces and their evaluation in patients with temporal lobe epilepsy. AB - Most studies assessing facial affect recognition in patients with TLE reported emotional disturbances in patients with TLE. Results from the few fMRI studies assessing neural correlates of affective face processing in patients with TLE are divergent. Some, but not all, found asymmetrical mesiotemporal activations, i.e., stronger activations within the hemisphere contralateral to seizure onset. Little is known about the association between neural correlates of affect processing and subjective evaluation of the stimuli presented. Therefore, we investigated the neural correlates of processing dynamic fearful faces in 37 patients with mesial temporal lobe epilepsy (TLE; 18 with left-sided TLE (lTLE), 19 with right-sided TLE (rTLE)) and 20 healthy subjects. We additionally assessed individual ratings of the fear intensity and arousal perception of the fMRI stimuli and correlated these data with the activations induced by the fearful face paradigm and activation lateralization within the mesiotemporal structures (in terms of individual lateralization indices, LIs). In healthy subjects, whole-brain analysis showed bilateral activations within a widespread network of mesial and lateral temporal, occipital, and frontal areas. The patient groups activated different parts of this network. In patients with lTLE, we found predominantly right-sided activations within the mesial and lateral temporal cortices and the superior frontal gyrus. In patients with rTLE, we observed bilateral activations in the posterior regions of the lateral temporal lobe and within the occipital cortex. Mesiotemporal region-of-interest analysis showed bilateral symmetric activations associated with watching fearful faces in healthy subjects. According to the region of interest and LI analyses, in the patients with lTLE, mesiotemporal activations were lateralized to the right hemisphere. In the patients with rTLE, we found left-sided mesiotemporal activations. In patients with lTLE, fear ratings were comparable to those of healthy subjects and were correlated with relatively stronger activations in the right compared to the left amygdala. Patients with rTLE showed significantly reduced fear ratings compared to healthy subjects, and we did not find associations with amygdala lateralization. Although we found stronger activations within the contralateral mesial temporal lobe in the majority of all patients, our results suggest that only in the event of left-sided mesiotemporal damage is the right mesial temporal lobe able to preserve intact facial fear recognition. In the event of right-sided mesiotemporal damage, fear recognition is disturbed. This underlines the hypothesis that the right amygdala is biologically predisposed to processing fear, and its function cannot be fully compensated in the event of right-sided mesiotemporal damage. PMID- 24210458 TI - Healthcare utilization of patients with epilepsy in Yuma County, Arizona: do disparities exist? AB - The aim of this study was to describe the disparities in healthcare utilization and costs between Hispanic and non-Hispanic patients with seizures or epilepsy. We reviewed the insurance status and healthcare resource utilization data from 2005 to 2008 for all patients with seizures and epilepsy seen at the Yuma Regional Medical Center (YRMC). Charges for medical services provided to Hispanic patients with epilepsy between the ages of 18 and 49 were significantly less than those for non-Hispanic patients with epilepsy (Hispanic: $3167.63 versus non Hispanic: $5154.36, P<0.001). Taking into account the differences in insurance status, setting of care, and total number of procedures, we still saw a significant difference in charges between the two groups at the outpatient settings. These data differ from currently available data on national and Eastern US Hispanic patients with epilepsy, suggesting that patients in this border community are somehow different from Hispanics elsewhere in the US. PMID- 24210459 TI - Neural generators of psychogenic seizures: evidence from intracranial and extracranial brain recordings. AB - Psychogenic seizures (PSs) convincingly mimic seizure phenomena but with no underlying epileptic activity. However, not much is known about their neurophysiological basis. We had the rare opportunity to analyze intracranial brain recordings of PSs occurring besides epileptic seizures (ESs), which identified distinct frequency changes over the parietal cortex. For further validation, we applied topographic frequency analysis to two other patients who presented PSs and ESs during long-term monitoring. The analysis revealed a power decrease in the theta band at the posterior parietal cortex in all three patients during PSs but not during ESs. These changes may reflect disturbed self referential processing associated with some PSs. PMID- 24210460 TI - Pregnancy-related knowledge and information needs of women with epilepsy: a systematic review. AB - For women with epilepsy (WWE), pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs (AEDs) versus the risks of having seizures during pregnancy. However, qualitative research suggests that many WWE remain uninformed about the risks associated with epilepsy and pregnancy and may, therefore, be making uninformed decisions about their families. The objectives of this review were to determine the level of patient knowledge, their informational needs, and whether these needs concerning pregnancy and childbirth issues are met among WWE. Electronic databases searched were PsycINFO, MEDLINE, Embase, CINAHL, and Web of Science. Studies were included if they used quantitative methods to survey WWE aged 16years or older about their knowledge, access to information, or informational needs specifically regarding epilepsy and pregnancy. Twelve studies were identified and assessed for research standards using the Quality Index. Overall Quality Index score was only 7.1 out of 14, indicating significant design limitations of many included studies, including highly selective sampling methods and the use of unvalidated outcome measures. There was a paucity of studies investigating specific areas of women's knowledge and information needs. Overall, WWE reported adequate awareness, but limited knowledge, of key issues regarding pregnancy and childbirth. Across studies, many women reported not receiving information about these issues. Evidence suggested that many WWE wanted to receive more information - particularly about the risks of AEDs for their offspring - well in advance of choosing an AED or planning pregnancy. Women aged under 35years wanted the most information. Preconception counseling received by many WWE appears insufficient, risking uninformed decision making about pregnancy. Further research is needed to investigate the barriers that WWE face in accessing, receiving, and retaining appropriate information. PMID- 24210461 TI - Patient satisfaction with temporal lobectomy/selective amygdalohippocampectomy for temporal lobe epilepsy and its relationship with Engel classification and the side of lobectomy. AB - PURPOSE: The aim of this study was to investigate not only the effectiveness of epilepsy surgery in improving seizure control but also patient satisfaction with the result of the procedure in a sample of patients operated on at a specialized epilepsy unit. METHODS: Patients with temporal lobe epilepsy who had undergone epilepsy surgery (temporal lobectomy/amygdalohippocampectomy) were interviewed in a standardized telephone survey about their satisfaction with the results of the surgery. The morbidity of the surgery was also analyzed retrospectively. The initial study population consisted of 6 amygdalohippocampectomy and 102 temporal lobectomy patients and was reduced to a final sample consisting of 4 amygdalohippocampectomy and 67 lobectomy patients, as the other patients were not available for interview. Surgical results were based on the Engel classification, and satisfaction with the surgery was assessed by asking patients to rate their result and state whether they would make the same decision (to be operated on) again. RESULTS: A significant number of patients classified as Engel I or II, who considered the surgical outcome good or excellent, said they would have the surgery again (p<0.001). Left temporal lobectomy patients whose results fell in the Engel III/IV bracket were less satisfied (p=0.001) than right temporal lobectomy patients with the same Engel classifications (0.048). Left temporal lobectomy patients who were classified as Engel class III and IV were less likely to have the surgery again if they had the choice (p=0.016). DISCUSSION: Patient satisfaction with the results of epilepsy surgery may depend not only on achieving seizure control but also on the temporal lobe resected. Since worse results were associated with lower satisfaction rates only for left temporal resection patients, it is possible that the cognitive consequences of this procedure compound the worse surgical result, leading to decreased satisfaction. PMID- 24210462 TI - Australia's seizure divide - indigenous versus non-indigenous seizure hospitalization. AB - Indigenous Australians suffer the highest mortality and morbidity rates of any ethnic minority in the developed world. To determine if the health outcome gulf between indigenous and non-indigenous Australians also applied to seizures, we conducted a retrospective analysis of seizure hospitalization (1998-2004) based on ethnicity (indigenous (I) and non-indigenous (NI)) for four Australian jurisdictions - Northern Territory (NT), Queensland (Qld), South Australia (SA), and Western Australia (WA). Total admissions were converted to age-standardized rates (ASR) and I/NI ASR ratios (I/NIRR) and compared across multiple variables. The summed admission (combined jurisdictions over six years) was 71,185 (I=11,593 and NI=59,592). Seizure hospitalization rate was always higher in the indigenous population (six-year I/NIRR - NT=5.6, Qld=4.0, SA=6.4, and WA=10.9; combined jurisdictions=5.6). Disparity was greatest for ages 40-64years (13.8) and 15 39years (7.0) and for indigenous males (7.4). As socioeconomic status rose, non indigenous admission rates fell (ASR=1.7 to 1.1), yet indigenous admission rates rose (ASR=7.9 to 14.0). Indigenous emergency to elective admission ratios were higher (I=27 and NI=8), as were readmissions (1.5-2 fold), self-discharge separations (I=9.4% and NI=1.4%), bed days (I/NIRR=5.1), and admissions with an additional diagnosis (I/NIRR=3.3) or procedure (I/NIRR=3.4). Indigenous Australians maintained disproportionately high rates of emergency seizure hospitalization; from 1998 to 2004, the combined jurisdiction rate was more than five times the mean non-indigenous rate. Indigenous males aged 15-64years were overrepresented. Indigenous patients had lengthier admissions but higher self discharge and readmission rates. The socioeconomic data raise the concern that social disadvantage restricts access to hospital-based seizure care for indigenous patients. PMID- 24210463 TI - Vagus nerve stimulation in pediatric patients: Is it really worthwhile? AB - Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case-control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group - 1.33+/-1.45years; controls - 3.23+/-3.11; p=0.0001), abnormal findings in neurological examination (p=0.01), history of previous ineffective epilepsy surgery (p=0.03), and baseline seizure frequency (p=0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy. PMID- 24210464 TI - Research on psychosocial aspects of epilepsy in Arab countries: a review of literature. AB - This study reviewed research conducted on the psychological aspects of epilepsy in Arab countries. Several databases (Medline, PubMed, Science Direct, Springer Link, and PsycInfo) were searched using the following two sets of search words: (1) Arab, Jordan, Lebanon, United Arab Emirates (UAE), Bahrain, Qatar, Kuwait, Oman, Saudi Arabia, Syria, Iraq, Egypt, Yemen, Tunisia, Libya, Morocco, Algiers, Palestine, Mauritania, Djibouti, Sudan, Comoros, and Somalia; and (2) epilepsy, seizure disorders, and convulsive disorders. Fifty-one studies were conducted in 12 Arab states. Social/emotional, employment, and other problems; knowledge and attitudes; and quality of life (QOL) were the most commonly measured parameters of psychosocial aspects of epilepsy in Arab countries. Results revealed elevated levels of depression and anxiety, a decline in cognitive function, various behavioral problems, sexual dysfunction, and underemployment among persons with epilepsy (PWE). Misconceptions about epilepsy were found to be prevalent. While many studies reported limited knowledge of epilepsy, some studies found an average knowledge. Negative attitudes toward epilepsy were reported in most studies, and moderately positive attitudes were reported in some studies. Finally, PWE showed low overall QOL scores in the majority of studies. PMID- 24210465 TI - Paranoid psychosis and cognitive impairment associated with hepatitis C antiviral therapy. AB - OBJECTIVE: To report a case of paranoid psychosis and cognitive impairment associated with Hepatitis C virus (HCV) antiviral therapy. METHODS: Case report. RESULTS: A 55-year-old male presented with paranoid psychosis and cognitive impairment, 4 months after initiating interferon-based HCV antiviral therapy. His psychosis resolved with discontinuation of therapy and initiation of risperidone, but his cognitive impairment persisted. His psychosis also re-emerged months later when attempting to titrate down his risperidone. Brain MRI demonstrated bilateral asymmetric subcortical and deep white matter changes, which were non specific but may have rendered him susceptible to neuropsychiatric sequelae of antiviral therapy. CONCLUSION: This case emphasizes the importance of neuropsychiatric screening and monitoring of patients being treated with interferon-based therapy for HCV, particularly if there is evidence of previous neurologic disease. PMID- 24210466 TI - Concordance of out-of-hospital and emergency department cardiac arrest resuscitation with documented end-of-life choices in Oregon. AB - STUDY OBJECTIVE: Resuscitation measures should be guided by previous patient choices about end-of-life care, when they exist; however, documentation of these choices can be unclear or difficult to access. We evaluate the concordance of a statewide registry of actionable resuscitation orders unique to Oregon with out of-hospital and emergency department (ED) care provided for patients found by emergency medical services (EMS) in out-of-hospital cardiac arrest. METHODS: This was a retrospective cohort study of patients found by EMS providers in out-of hospital cardiac arrest in 5 counties in 2010. We used probabilistic linkage to match patients found in out-of-hospital cardiac arrest with previously signed documentation of end-of-life decisions in the Oregon Physician Orders for Life Sustaining Treatment (POLST) registry. We evaluated resuscitation interventions in the field and ED. RESULTS: There were 1,577 patients found in out-of-hospital cardiac arrest, of whom 82 had a previously signed POLST form. Patients with POLST do-not-resuscitate orders for whom EMS was called had resuscitation withheld or ceased before hospital admission in 94% of cases (95% confidence interval [CI] 83% to 99%). Compared with patients with no POLST or known do-not resuscitate orders, more patients with attempt resuscitation POLST orders had field resuscitation attempted (84% versus 60%; difference 25%; 95% CI 12% to 37%) and were admitted to hospitals (38% versus 17%; difference 20%; 95% CI 3% to 37%), with no documented misinterpretations of the form once CPR was initiated. CONCLUSION: In this sample of patients in out-of-hospital cardiac arrest, out-of hospital and ED care was generally concordant with previously documented end-of life orders in the setting of critical illness. Further research is needed to compare the effectiveness of Oregon's POLST system to other methods of end-of life order documentation. PMID- 24210467 TI - Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: a cohort study. AB - We conducted a prospective cohort study in a single tertiary hospital with the aim of assessing predictors of multidrug-resistant bacteremia in 307 cases of febrile neutropenia in adult patients with cancer. On multivariate analysis using stepwise logistic regression, age (P = .009), duration of neutropenia (P = .022), and presence of an indwelling central venous catheter (P = .022) were associated with bloodstream infection by multidrug-resistant bacteria. PMID- 24210468 TI - Emerging methods for the fabrication of polymer capsules. AB - Hollow polymer capsules are attracting increasing research interest due to their potential application as drug delivery vectors, sensors, biomimetic nano- or multi-compartment reactors and catalysts. Thus, significant effort has been directed toward tuning their size, composition, morphology, and functionality to further their application. In this review, we provide an overview of emerging techniques for the fabrication of polymer capsules, encompassing: self-assembly, layer-by-layer assembly, single-step polymer adsorption, bio-inspired assembly, surface polymerization, and ultrasound assembly. These techniques can be applied to prepare polymer capsules with diverse functionality and physicochemical properties, which may fulfill specific requirements in various areas. In addition, we critically evaluate the challenges associated with the application of polymer capsules in drug delivery systems. PMID- 24210469 TI - How self-care education in ventricular assist device programs is organized and provided: a national study. AB - OBJECTIVE: To describe the care delivery structure and elements used for patient self-care education in ventricular assist device (VAD) programs. BACKGROUND: Use of VADs as destination therapy and to sustain organ function until cardiac transplantation has increased 517% since 2007. Elements of VAD-specific self-care education have not been described. METHODS: A 26-item survey measuring VAD self care education resource use, organizational, employment, behavioral and labor variables was sent to VAD coordinators at all US VAD centers (N = 111) in 2011. Two subsequent mailings yielded a 63% (n = 71) return rate. Analysis included descriptive statistics and cluster analysis. RESULTS: Element use varied across programs. Reliance on single educational and evaluation methods, and lack of return demonstration were noted. VAD coordinators reported extensive caregiver, hospital provider, and community educational responsibilities in addition to patient self-care education. CONCLUSIONS: VAD self-care education programs varied by hospital. Future research is needed to determine if specific care delivery structures or elements used in self-care education improve VAD patient outcomes. PMID- 24210470 TI - Numerical modelling of mass transport in an arterial wall with anisotropic transport properties. AB - Coronary artery disease results in blockages or narrowing of the artery lumen. Drug eluting stents (DES) were developed to replace bare metal stents in an effort to combat re-blocking of the diseased artery following treatment. The numerical models developed within this study focus on representing the changing trends of drug delivery from an idealised DES in an arterial wall with an anisotropic ultra-structure. To reduce the computational burden of solving coupled physics problems, a model reduction strategy was adopted. Particular focus has been placed upon adequately modelling the influence of strut compression as there is a paucity of numerical studies that account for changes in transport properties in compressed regions of the arterial wall due to stent deployment. This study developed an idealised numerical modelling framework to account for the changes in the directionally dependent porosity and tortuosities of the arterial wall as a result of radial strut compression. The results show that depending on the degree of strut compression, trends in therapeutic drug delivery within the arterial wall can be either increased or decreased. The study highlights the importance of incorporating compression into numerical models to better represent transport within the arterial wall and suggests an appropriate numerical modelling framework that could be utilised in more realistic patient specific arterial geometries. PMID- 24210471 TI - Enhanced boundary lubrication properties of engineered menisci by lubricin localization with insulin-like growth factor I treatment. AB - In this study we analyzed the effects of IGF-I on the boundary lubricating ability of engineered meniscal tissue using a high density collagen gel seeded with meniscal fibrochondrocytes. Biochemical, histological, immunohistochemical, and tribological analyses were carried out to determine a construct's ability to functionally localize lubricin. Our study revealed that supplementation with IGF I enhanced both the proliferation of cells within the construct as well as enhanced the anabolic activity of the seeded cells. Growth factor supplementation also facilitated the localization of ECM constituents (i.e. fibronectin and type II collagen) near the tissue surface that are important for the localization of lubricin, a boundary lubricant. Consequently, we found localized lubricin in the constructs supplemented with IGF-I. Tribologically, we demonstrated that lubricin serves as a boundary lubricant adsorbed to native meniscal surfaces. Lubricin removal from the native meniscus surface increased boundary friction coefficient by 40%. For the engineered constructs, the lubricin localization facilitated by growth factor supplementation also reduced friction coefficient by a similar margin, but similar results were not evident in control constructs. This study demonstrates that the use of growth factors in meniscal tissue engineering can enhance tribological properties by facilitating the localization of boundary lubricants at the surface of engineered tissue. PMID- 24210472 TI - Numerical investigation of mass transport through patient-specific deformed aortae. AB - Blood flow in human arteries has been investigated using computational fluid dynamics tools. This paper considers flow modeling through three aorta models reconstructed from cross-sectional magnetic resonance scans of female patients. One has the normal control configuration, the second has elongation of the transverse aorta, and the third has tortuosity of the aorta with stenosis. The objective of this study is to determine the impact of aortic abnormal geometries on the wall shear stress (WSS), luminal surface low-density lipoproteins (LDLs) concentration, and oxygen flux along the arterial wall. The results show that the curvature of the aortic arch and the stenosis have significant effects on the blood flow, and in turn, the mass transport. The location of hypoxia areas can be predicted well by ignoring the effect of hemoglobin on the oxygen transport. However, this simplification indeed alters the absolute value of Sherwood number on the wall. PMID- 24210473 TI - The effects of femoral graft placement on cartilage thickness after anterior cruciate ligament reconstruction. AB - Altered joint motion has been thought to be a contributing factor in the long term development of osteoarthritis after ACL reconstruction. While many studies have quantified knee kinematics after ACL injury and reconstruction, there is limited in vivo data characterizing the effects of altered knee motion on cartilage thickness distributions. Thus, the objective of this study was to compare cartilage thickness distributions in two groups of patients with ACL reconstruction: one group in which subjects received a non-anatomic reconstruction that resulted in abnormal joint motion and another group in which subjects received an anatomically placed graft that more closely restored normal knee motion. Ten patients with anatomic graft placement (mean follow-up: 20 months) and 12 patients with non-anatomic graft placement (mean follow-up: 18 months) were scanned using high-resolution MR imaging. These images were used to generate 3D mesh models of both knees of each patient. The operative and contralateral knee models were registered to each other and a grid sampling system was used to make site-specific comparisons of cartilage thickness. Patients in the non-anatomic graft placement group demonstrated a significant decrease in cartilage thickness along the medial intercondylar notch in the operative knee relative to the intact knee (8%). In the anatomic graft placement group, no significant changes were observed. These findings suggest that restoring normal knee motion after ACL injury may help to slow the progression of degeneration. Therefore, graft placement may have important implications on the development of osteoarthritis after ACL reconstruction. PMID- 24210475 TI - A 3D lower limb musculoskeletal model for simultaneous estimation of musculo tendon, joint contact, ligament and bone forces during gait. AB - Musculo-tendon forces and joint reaction forces are typically estimated using a two-step method, computing first the musculo-tendon forces by a static optimization procedure and then deducing the joint reaction forces from the force equilibrium. However, this method does not allow studying the interactions between musculo-tendon forces and joint reaction forces in establishing this equilibrium and the joint reaction forces are usually overestimated. This study introduces a new 3D lower limb musculoskeletal model based on a one-step static optimization procedure allowing simultaneous musculo-tendon, joint contact, ligament and bone forces estimation during gait. It is postulated that this approach, by giving access to the forces transmitted by these musculoskeletal structures at hip, tibiofemoral, patellofemoral and ankle joints, modeled using anatomically consistent kinematic models, should ease the validation of the model using joint contact forces measured with instrumented prostheses. A blinded validation based on four datasets was made under two different minimization conditions (i.e., C1 - only musculo-tendon forces are minimized, and C2 - musculo tendon, joint contact, ligament and bone forces are minimized while focusing more specifically on tibiofemoral joint contacts). The results show that the model is able to estimate in most cases the correct timing of musculo-tendon forces during normal gait (i.e., the mean coefficient of active/inactive state concordance between estimated musculo-tendon force and measured EMG envelopes was C1: 65.87% and C2: 60.46%). The results also showed that the model is potentially able to well estimate joint contact, ligament and bone forces and more specifically medial (i.e., the mean RMSE between estimated joint contact force and in vivo measurement was C1: 1.14BW and C2: 0.39BW) and lateral (i.e., C1: 0.65BW and C2: 0.28BW) tibiofemoral contact forces during normal gait. However, the results remain highly influenced by the optimization weights that can bring to somewhat aphysiological musculo-tendon forces. PMID- 24210474 TI - Computational model of the in vivo development of a tissue engineered vein from an implanted polymeric construct. AB - Advances in vascular tissue engineering have been tremendous over the past 15 years, yet there remains a need to optimize current constructs to achieve vessels having true growth potential. Toward this end, it has been suggested that computational models may help hasten this process by enabling time-efficient parametric studies that can reduce the experimental search space. In this paper, we present a first generation computational model for describing the in vivo development of a tissue engineered vein from an implanted polymeric scaffold. The model was motivated by our recent data on the evolution of mechanical properties and microstructural composition over 24 weeks in a mouse inferior vena cava interposition graft. It is shown that these data can be captured well by including both an early inflammatory-mediated and a subsequent mechano-mediated production of extracellular matrix. There remains a pressing need, however, for more data to inform the development of next generation models, particularly the precise transition from the inflammatory to the mechanobiological dominated production of matrix having functional capability. PMID- 24210476 TI - Resonance-based oscillations could describe human gait mechanics under various loading conditions. AB - The oscillatory behavior of the center of mass (CoM) and the corresponding ground reaction force (GRF) of human gait for various gait speeds can be accurately described in terms of resonance using a spring-mass bipedal model. Resonance is a mechanical phenomenon that reflects the maximum responsiveness and energetic efficiency of a system. To use resonance to describe human gait, we need to investigate whether resonant mechanics is a common property under multiple walking conditions. Body mass and leg stiffness are determinants of resonance; thus, in this study, we investigated the following questions: (1) whether the estimated leg stiffness increased with inertia, (2) whether a resonance-based CoM oscillation could be sustained during a change in the stiffness, and (3) whether these relationships were consistently observed for different walking speeds. Seven healthy young subjects participated in over-ground walking trials at three different gait speeds with and without a 25-kg backpack. We measured the GRFs and the joint kinematics using three force platforms and a motion capture system. The leg stiffness was incorporated using a stiffness parameter in a compliant bipedal model that best fitted the empirical GRF data. The results showed that the leg stiffness increased with the load such that the resonance-based oscillatory behavior of the CoM was maintained for a given gait speed. The results imply that the resonance-based oscillation of the CoM is a consistent gait property and that resonant mechanics may be useful for modeling human gait. PMID- 24210477 TI - Intervertebral disc creep behavior assessment through an open source finite element solver. AB - Degenerative Disc Disease (DDD) is one of the largest health problems faced worldwide, based on lost working time and associated costs. By means of this motivation, this work aims to evaluate a biomimetic Finite Element (FE) model of the Intervertebral Disc (IVD). Recent studies have emphasized the importance of an accurate biomechanical modeling of the IVD, as it is a highly complex multiphasic medium. Poroelastic models of the disc are mostly implemented in commercial finite element packages with limited access to the algorithms. Therefore, a novel poroelastic formulation implemented on a home-developed open source FE solver is briefly addressed throughout this paper. The combination of this formulation with biphasic osmotic swelling behavior is also taken into account. Numerical simulations were devoted to the analysis of the non degenerated human lumbar IVD time-dependent behavior. The results of the tests performed for creep assessment were inside the scope of the experimental data, with a remarkable improvement of the numerical accuracy when compared with previously published results obtained with ABAQUS((r)). In brief, this in development open-source FE solver was validated with literature experimental data and aims to be a valuable tool to study the IVD biomechanics and DDD mechanisms. PMID- 24210478 TI - Head impact exposure in male and female collegiate ice hockey players. AB - The purpose of this study was to quantify head impact exposure (frequency, location and magnitude of head impacts) for individual male and female collegiate ice hockey players and to investigate differences in exposure by sex, player position, session type, and team. Ninety-nine (41 male, 58 female) players were enrolled and 37,411 impacts were recorded over three seasons. Frequency of impacts varied significantly by sex (males: 287 per season, females: 170, p<0.001) and helmet impact location (p<0.001), but not by player position (p=0.088). Head impact frequency also varied by session type; both male and female players sustained more impacts in games than in practices (p<0.001), however the magnitude of impacts did not differ between session types. There was no difference in 95th percentile peak linear acceleration between sexes (males: 41.6 g, females: 40.8 g), but 95th percentile peak rotational acceleration and HITsp (a composite severity measure) were greater for males than females (4424, 3409 rad/s(2), and 25.6, 22.3, respectively). Impacts to the back of the helmet resulted in the greatest 95th percentile peak linear accelerations for males (45.2 g) and females (50.4 g), while impacts to the side and back of the head were associated with the greatest 95th percentile peak rotational accelerations (males: 4719, 4256 rad/sec(2), females: 3567, 3784 rad/sec(2) respectively). It has been proposed that reducing an individual's head impact exposure is a practical approach for reducing the risk of brain injuries. Strategies to decrease an individual athlete's exposure need to be sport and gender specific, with considerations for team and session type. PMID- 24210479 TI - The effects of forage particle length and exogenous phytase inclusion on phosphorus digestion and absorption in lactating cows. AB - Accurate estimates of phosphorus (P) availability from feed are needed to allow P requirements to be met with reduced P intake, thus reducing P excretion by livestock. Exogenous phytase supplementation in poultry and swine diets improves bioavailability of P, and limited research suggests that this strategy may have some application in dairy cattle rations. The effects of exogenous phytase and forage particle length on site and extent of P digestion were evaluated with 5 ruminally and ileally cannulated lactating cows (188 +/- 35 d in milk). Cows were assigned in a 2 * 2 factorial arrangement of treatments in 2 incomplete Latin squares with four 21-d periods. Diets contained P slightly in excess of National Research Council requirements with all P from feed sources. During the last 4d of each period, total mixed ration, refusals, omasal, ileal, and fecal samples were collected and analyzed for total P, inorganic P (Pi), and phytate (Pp). Total P intake was not influenced by dietary treatments but Pp intake decreased and Pi intake increased with supplemental phytase, suggesting rapid action of the enzyme in the total mixed ration after mixing. Omasal flow of Pi decreased with phytase supplementation, but we observed no effect of diet in ileal flow or small intestinal digestibility of any P fraction. Fecal excretion of total P was slightly higher and Pp excretion was lower for cows receiving diets supplemented with phytase. Milk yield and composition were unaffected by diets. When phytase was added to the mixed ration, dietary Pp was rapidly degraded before intake and total-tract Pp digestion was increased. The lack of effect of phytase supplementation on dietary P utilization was probably because these late lactation cows had a low P requirement and were fed P-adequate diets. PMID- 24210480 TI - Effects of level of nutrient intake and age on mammalian target of rapamycin, insulin, and insulin-like growth factor-1 gene network expression in skeletal muscle of young Holstein calves. AB - The molecular mechanisms by which level of nutrient intake enhances skeletal muscle growth in young ruminants are not fully understood. We examined mammalian target of rapamycin (mTOR), insulin, and insulin-like growth factor-1 (IGF-1) gene network expression in semitendinosus muscle tissue of young male Holstein calves fed a conventional milk replacer plus conventional starter (CON) or an enhanced milk replacer plus high-protein starter (ENH) for 5 wk followed by a conventional starter or a high-protein starter until 10 wk of age. Feeding ENH led to greater concentration of plasma IGF-1 and leptin and greater carcass protein and fat mass throughout the study. Despite the greater plasma IGF-1 and protein mass at wk 5, calves fed ENH had lower expression of IGF1R, INSR, and RPS6KB1 but greater expression of IRS1 and PDPK1 in muscle tissue. Except for IGF1R expression, which did not differ at wk 10, these differences persisted at wk 10, suggesting a long-term effect of greater nutrient intake on physiological and molecular mechanisms. Components of mTOR complex (mTORC)1 and mTORC2 (RICTOR and RPTOR) and FOXO1 expression decreased by wk 10 regardless of diet. Overall, the present data revealed that greater nutrient intake throughout the milk-fed and early postweaning phase alters body mass composition partly by altering hormonal and molecular profiles of genes associated with glucose and amino acid signaling. Those networks may play a crucial role in coordinating neonatal muscle growth and metabolism in response to level of nutrient intake. PMID- 24210481 TI - Noninferiority trial on the efficacy of premilking teat disinfectant against naturally occurring new intramammary infections using a novel 2-step diagnostic process. AB - The objective of the study was to evaluate premilking teat disinfectant efficacy with the use of a novel diagnostic protocol against a positive control. The evaluation of efficacy was based on establishing noninferiority of a new premilking teat disinfectant compared with an existing premilking teat disinfectant. Approximately 200 cows were randomly allocated to 1 of 2 groups. Study personnel were blinded as to cow allocation and identification of the premilking disinfectants. Quarters were disinfected using a dip cup before milking with either the control or experimental product. The disinfectant was left on the teat for approximately 30s before being wiped off in preparation for milking. Quarter-level bacteriological infection status was established at the beginning of the study and quarter milk samples were collected biweekly thereafter. Bacteriological analyses were performed only when somatic cell counts in milk samples crossed a parity-specific threshold. Poisson regression models were used to analyze data. The difference in the rate of new intramammary infections was small and the upper bound of the 95% confidence interval of the rate difference was smaller than a predefined noninferiority limit. Based on the observed difference in new intramammary infections rate between the experimental and control product, it was concluded that the experimental disinfectant was not inferior compared with the positive control. The protocol used in this study proposes a valid and economically attractive methodology to evaluate the efficacy of teat disinfectants relative to a positive control. PMID- 24210482 TI - Effects of feed additives on rumen and blood profiles during a starch and fructose challenge. AB - We evaluated the effect of feed additives on the risk of ruminal acidosis in Holstein heifers (n = 40) fed starch and fructose in a challenge study. Heifers were randomly allocated to feed additive groups (n = 8 heifers/group): (1) control (no additives); (2) virginiamycin (VM); (3) monensin + tylosin (MT); (4) monensin + live yeast (MLY); and (5) sodium bicarbonate + magnesium oxide (BUF). Heifers were fed 2.5% of body weight (BW) dry matter intake (DMI) per day of a total mixed ration (62:38 forage:concentrate) and feed additives for a 20-d adaptation period. Fructose (0.1% of BW/d) was included for the last 10d of the adaptation period. On d 21, heifers were fed to target a DMI of 1.0% of BW of wheat, fructose at 0.2% of BW, and their feed additives. Rumen fluid samples obtained by stomach tube and blood samples were collected weekly as well as during a 3.6-h period on challenge day (d 21). Virginiamycin and BUF groups maintained a consistently high DMI across the 20-d adaptation period. The MLY heifers had low DMI of the challenge ration. Average daily gain and feed conversion ratio were not affected by feed additives. All rumen and plasma measures changed weekly over adaptation and over the challenge sampling period with the exception of rumen total lactate and histamine concentrations, plasma oxidative stress index, and ceruloplasmin. Substantial within- and between-group variation was observed in rumen and plasma profiles at challenge sampling. No significant group changes were observed in rumen total volatile fatty acids, propionate, acetate-to-propionate ratio, isobutyrate, caproate, isovalerate, total lactate, d- and l-lactate, and pH measures on challenge day. Acetate concentration was increased in the BUF and control groups on challenge day. Butyrate concentration was lower in the MLY and MT groups compared with other groups at challenge. Valerate concentrations were lowest in the control, VM, and BUF groups and lactate concentrations were numerically lower in the MLY, VM, and BUF groups. Total lactate concentrations were >10mM for each group throughout the challenge. Ammonia concentrations were lower in the MLY and MT groups. Histamine concentrations were decreased in MLY and increased in the VM and BUF groups. Plasma oxidative stress measures were not influenced by feed additives weekly or on challenge day, except for an increase in biological antioxidant potential in the control, VM, and MT groups on challenge day. Despite the large within-animal variation, all feed additives modified rumen function and may influence the risk of acidosis by different mechanisms; however, none stabilized the rumen in all heifers. PMID- 24210483 TI - Effects of time and sampling location on concentrations of beta-hydroxybutyric acid in dairy cows. AB - Two trials were conducted to examine factors potentially influencing the measurement of blood beta-hydroxybutyric acid (BHBA) in dairy cows. The objective of the first trial was to study effects of sampling time on BHBA concentration in continuously fed dairy cows. Furthermore, we determined test characteristics of a single BHBA measurement at a random time of the day to diagnose subclinical ketosis considering commonly used cut-points (1.2 and 1.4 mmol/L). Finally, we set out to evaluate if test characteristics could be enhanced by repeating measurements after different time intervals. During 4 herd visits, a total of 128 cows (8 to 28 d in milk) fed 10 times daily were screened at 0900 h and preselected by BHBA concentration. Blood samples were drawn from the tail vessels and BHBA concentrations were measured using an electronic BHBA meter (Precision Xceed, Abbott Diabetes Care Ltd., Witney, UK). Cows with BHBA concentrations >=0.8 mmol/L at this time were enrolled in the trial (n=92). Subsequent BHBA measurements took place every 3h for a total of 8 measurements during 24 h. The effect of sampling time on BHBA concentrations was tested in a repeated-measures ANOVA repeating sampling time. Sampling time did not affect BHBA concentrations in continuously fed dairy cows. Defining the average daily BHBA concentration calculated from the 8 measurements as the gold standard, a single measurement at a random time of the day to diagnose subclinical ketosis had a sensitivity of 0.90 or 0.89 at the 2 BHBA cut-points (1.2 and 1.4 mmol/L). Specificity was 0.88 or 0.90 using the same cut-points. Repeating measurements after different time intervals improved test characteristics only slightly. In the second experiment, we compared BHBA concentrations of samples drawn from 3 different blood sampling locations (tail vessels, jugular vein, and mammary vein) of 116 lactating dairy cows. Concentrations of BHBA differed in samples from the 3 sampling locations. Mean BHBA concentration was 0.3 mmol/L lower when measured in the mammary vein compared with the jugular vein and 0.4 mmol/L lower in the mammary vein compared with the tail vessels. We conclude that to measure BHBA, blood samples of continuously fed dairy cows can be drawn at any time of the day. A single measurement provides very good test characteristics for on-farm conditions. Blood samples for BHBA measurement should be drawn from the jugular vein or tail vessels; the mammary vein should not be used for this purpose. PMID- 24210484 TI - Effect of Sicilian pasture feeding management on content of alpha-tocopherol and beta-carotene in cow milk. AB - This study was performed to evaluate alpha-tocopherol and beta-carotene contents of pasture milk under ordinary Sicilian farming conditions. Fourteen dairy farms were allocated into 2 balanced groups on the basis of cultivated (CULT) or spontaneous (SPO) pasture type feeding. Bulk milk per farm was collected 4 times from February through April at 3-wk intervals. Pasture botanical and diet composition, diet nutritional quality, milk yield and composition were estimated each time. Pasture intake levels were calculated based on feed analyses, hay and concentrate amounts fed, and milk yield and chemical composition. According to pasture intake, the farms were split into low pasture intake (LPI; <29.5% of dry matter) and high pasture intake (HPI; >29.5% of dry matter) groups. Milk samples per farm were analyzed for alpha-tocopherol and beta-carotene contents by HPLC. The SPO group had higher levels of alpha-tocopherol and beta-carotene in milk (0.7 and 0.3 mg/L, respectively) and milk fat (19.0 and 7.5 mg/kg fat, respectively) compared with the CULT group in milk (0.5 and 0.2 mg/L, respectively) and milk fat (14.6 and 4.9 mg/kg, respectively). High pasture intake compared with LPI increased alpha-tocopherol in milk fat (18.0 and 16.0 mg/kg of fat, respectively). However, only in the SPO (not in CULT), HPI compared with LPI increased milk alpha-tocopherol (0.8 vs. 0.6 mg/L, respectively), milk beta-carotene (0.3 vs. 0.2 mg/L, respectively), and milk fat beta-carotene (8.4 vs. 6.6 mg/kg, respectively). Results may be related to the different botanical composition of the respective pasture types and pasture intake. Spontaneous pasture compared with CULT contained a higher mass proportion of Asteraceae, Fabaceae, Cruciferae, Euphorbiaceae, and Malvaceae plants. Milk and milk fat alpha-tocopherol levels were higher on test-days (TD)-1, TD-2, and TD-4 compared with TD-3. For HPI farms, milk fat beta-carotene content was higher on the first 2 TD compared with the last 2 TD. These differences could be related to plant biological stage. On Sicilian dairy farms, the highest milk alpha-tocopherol and beta-carotene contents may be obtained feeding high levels of SPO pasture in the spring. PMID- 24210486 TI - Yield, changes in proteolysis, and sensory quality of Prato cheese produced with different coagulants. AB - The objective of this research was to compare the effect of 2 fungal proteases, one that is already commercially established as a milk-clotting agent and another produced at the laboratory scale, on Prato cheese composition, protein and fat recovery, yield, and sensory characteristics. Cheeses were produced according to the traditional protocol, using protease from the fungus Thermomucor indicae seudaticae N31 and commercial coagulant from Rhizomucor spp. as clotting agents. A 2*6 factorial design with 3 replications was performed: 2 levels of coagulants and 6 levels of storage time. After 5, 12, 19, 33, 43, and 53d of refrigerated storage (12 degrees C), cheeses were monitored for proteolysis, firmness, and casein degradation by capillary electrophoresis. Sensory acceptance was evaluated after 29d of manufacturing. The different coagulants did not statistically affect Prato cheese composition, protein and fat recovery, and yield. Both cheeses presented good sensory acceptance. Proteolysis increased and firmness decreased for both cheeses during the storage time, as expected for Prato cheese. Caseins were well separated by capillary electrophoresis and the results showed, with good resolution, that the cheeses exhibited similar protein hydrolysis profile. Both cheeses presented good sensory acceptance. The gathered data showed that the protease from T. indicae-seudaticae N31 presented similar action compared with the commercial enzyme, indicating its efficiency as clotting agent for Prato cheese manufacture. PMID- 24210485 TI - Short communication: the pharmacological peroxisome proliferator-activated receptor alpha agonist WY-14,643 increases expression of novel organic cation transporter 2 and carnitine uptake in bovine kidney cells. AB - Recent studies in rodents demonstrated that peroxisome proliferator-activated receptor alpha (PPARalpha), a central regulator of energy homeostasis, is an important transcriptional regulator of the gene encoding the carnitine transporter novel organic cation transporter 2 (OCTN2). Less is known with regard to the regulation of OCTN2 by PPARalpha and its role for carnitine transport in cattle, even though PPARalpha activation physiologically occurs in the liver of high-producing cows during early lactation. To explore the role of PPARalpha for OCTN2 expression and carnitine transport in cattle, we studied the effect of the PPARalpha activator WY-14,643 on the expression of OCTN2 in the presence and absence of PPARalpha antagonists and on OCTN2-mediated carnitine transport in the Madin-Darby bovine kidney (MDBK) cell line. The results show that WY-14,643 increases mRNA and protein levels of OCTN2, whereas co-treatment of MDBK cells with WY-14,643 and the PPARalpha antagonist GW6471 blocks the WY-14,643-induced increase in mRNA and protein levels of OCTN2 in bovine cells. In addition, treatment of MDBK cells with WY-14,643 stimulates specifically Na(+)-dependent carnitine uptake in MDBK cells, which is likely the consequence of the increased carnitine transport capacity of cells due to the elevated expression of OCTN2. In conclusion, our results indicate that OCTN2 expression and carnitine transport in cattle, as in rodents, are regulated by PPARalpha. PMID- 24210487 TI - Epilactose production by 2 cellobiose 2-epimerases in natural milk. AB - It was reported recently that cellobiose 2-epimerases (CE) from various aerobic microorganisms convert lactose to epilactose in defined buffer systems. In this study, we showed that CE from 2 mesophilic microorganisms, Flavobacterium johnsoniae and Pedobacter heparinus, were capable of converting lactose to prebiotic epilactose not only in buffer but also in a complex milk system. First, the 2 enzymes were separately cloned, recombinantly expressed in Escherichia coli, and purified by column chromatography. The production of F. johnsoniae CE was carried out in a stirred-tank reactor, indicating that future upscaling is possible. The bioconversions of milk lactose were carried out at an industrially relevant low temperature of 8 degrees C to avoid undesired microbial contaminations or chemical side reactions. Both enzymes were reasonably active at this low temperature, because of their origin from mesophilic organisms. The enzymes showed different operational stabilities over a 24-h time-course. A conversion yield of about 30 to 33% epilactose was achieved with both enzymes. No side products were detected other than epilactose. Therefore, CE may introduce an added value for particular dairy products by in situ production of the prebiotic sugar epilactose. PMID- 24210488 TI - The effect of relocation of whole-crop wheat and corn silages on their quality. AB - Whole-crop wheat and corn silages in 1.5-L anaerobic jars were exposed to air for 0 up to 48 h during their anaerobic storage period to simulate relocation of silages. Ensiling treatments included control (no additives) and either Koffosil T (Koffolk Inc., Petah Tikva, Israel) comprising a mixture of organic acids or Lactobacillus plantarum MTD1 (Ecosyl Products Ltd., Stokesley, UK). In the first set of experiments, the duration of exposure to air had little effect on ensiling parameters or on the aerobic stability of the final silages. In the second set of experiments, both the inoculant and duration of exposure to air had an effect on various fermentation parameters and on the aerobic stability of the final silages. We concluded that if the silages are of good quality, the duration of the relocation process has little effect on silage quality or its aerobic stability. However, if the silage contains any factor that may affect its aerobic stability, it is more sensitive to the time it takes to re-ensile the forage. PMID- 24210489 TI - Accuracy and precision of total mixed rations fed on commercial dairy farms. AB - Despite the significant time and effort spent formulating total mixed rations (TMR), it is evident that the ration delivered by the producer and that consumed by the cow may not accurately reflect that originally formulated. The objectives of this study were to (1) determine how TMR fed agrees with or differs from TMR formulation (accuracy), (2) determine daily variability in physical and chemical characteristics of TMR delivered (precision), and (3) investigate the relationship between daily variability in ration characteristics and group average measures of productivity [dry matter intake (DMI), milk yield, milk components, efficiency, and feed sorting] on commercial dairy farms. Twenty-two commercial freestall herds were visited for 7 consecutive days in both summer and winter months. Fresh and refusal feed samples were collected daily to assess particle size distribution, dry matter, and chemical composition. Milk test data, including yield, fat, and protein were collected from a coinciding Dairy Herd Improvement test. Multivariable mixed-effect regression models were used to analyze associations between productivity measures and daily ration variability, measured as coefficient of variation (CV) over 7d. The average TMR [crude protein=16.5%, net energy for lactation (NEL) = 1.7 Mcal/kg, nonfiber carbohydrates = 41.3%, total digestible nutrients = 73.3%, neutral detergent fiber=31.3%, acid detergent fiber=20.5%, Ca = 0.92%, p=0.42%, Mg = 0.35%, K = 1.45%, Na = 0.41%] delivered exceeded TMR formulation for NEL (+0.05 Mcal/kg), nonfiber carbohydrates (+1.2%), acid detergent fiber (+0.7%), Ca (+0.08%), P (+0.02%), Mg (+0.02%), and K (+0.04%) and underfed crude protein (-0.4%), neutral detergent fiber (-0.6%), and Na (-0.1%). Dietary measures with high day-to-day CV were average feed refusal rate (CV = 74%), percent long particles (CV = 16%), percent medium particles (CV = 7.7%), percent short particles (CV = 6.1%), percent fine particles (CV = 13%), Ca (CV = 7.7%), Mg (CV = 5.2%), and Na (CV = 10%). Every 0.5-percentage-point decrease in daily NEL (CV = 1.2 +/- 0.4%) was associated with 3.2 kg/d greater milk yield, 1.0 kg/d greater DMI, and 4.3% greater efficiency of production. Every 5-percentage-point decrease in variability in percent long particles (average percent long = 19.8 +/- 6.5; CV = 16.1 +/- 6.9%) in the TMR was associated with 1.2 kg/d greater milk yield and a 2.6% increase in efficiency of milk production. These results demonstrate the importance of ensuring TMR consistency to maximize DMI, production, and efficiency. PMID- 24210490 TI - Analysis of milking characteristics in New Zealand dairy cows. AB - The objective of this study was to describe the variation in milking characteristics, and factors associated with these traits, in grazing dairy cows milked without premilking stimulation. Milk yield, duration, and average and maximum milk flow rate data were collected from 38 farms in New Zealand at 2 time points (spring and autumn) during the 2010 to 2011 season. Subsequently, a second data set, allowing the generation of daily milk flow profiles, was collected from 2 farms in the 2011 to 2012 season. Corresponding animal data, such as breed, date of birth, and ancestry information, were extracted from the New Zealand Dairy Industry Good Animal Database (New Zealand Animal Evaluation Ltd., Hamilton, New Zealand). Residual milking duration (deviation from the regression line of milk yield on milking duration) was calculated, allowing the identification of fast-milking cows independent of milk yield. Variance components for the milking characteristics traits were estimated using an animal linear mixed model. The average milk yield was 10 kg/milking and the average milking duration was 360 s. The average milk flow rate was 1.8 kg/min and maximum milk flow 3.3 kg/min, with 44% of milk flow curves being classified as bimodal. Primiparous animals exhibited different milk flow profiles, with a lower maximum flow, than multiparous animals, possibly due to differences in cisternal capacity. Residual milking duration was shortest (-10s) in mid-lactation (121-180 d) and was 13s longer for Jersey compared with Friesian cows; however, it was 19s shorter when adjusted for energy content. Residual milking duration had a negligible genetic correlation (-0.07) with milk yield, indicating that selection for cows with shorter residual milking duration should have a negligible effect on milk yield. A heritability of 0.27 indicated that residual milking duration could be valuable as part of a breeding program. Knowledge of the distribution of milking durations for a given milk yield allows farmers to choose appropriate cluster-on time when using a maximum milking time strategy to improve milking efficiency. PMID- 24210491 TI - On the limited increase in validation reliability using high-density genotypes in genomic best linear unbiased prediction: observations from Fleckvieh cattle. AB - This study investigated reliability of genomic predictions using medium-density (40,089; 50K) or high-density (HD; 388,951) marker sets. We developed an approximate method to test differences in validation reliability for significance. Model-based reliability and the effect of HD genotypes on inflation of predictions were analyzed additionally. Genomic breeding values were predicted for at least 1,321 validation bulls based on phenotypes and genotypes of at least 5,324 calibration bulls by means of a linear model in milk, fat, and protein yield; somatic cell score; milkability; muscling; udder, feet, and legs score as well as stature. In total, 1,485 bulls were actually HD genotyped and HD genotypes of the other animals were imputed from 50K genotypes using FImpute software. Validation reliability was measured as the coefficient of determination of the weighted regression of daughter yield deviations on predicted breeding values divided by the reliability of daughter yield deviations and inflation was evaluated by the slope of this regression. Model-based reliability was calculated from the model. Distributions for validation reliability of 50K markers were derived by repeated sampling of 50,000-marker samples from HD to test differences in validation reliability statistically. Additionally, the benefit of HD genotypes in validation reliability was tested by repeated sampling of validation groups and calculation of the difference in validation reliability between HD and 50K genotypes for the sampled groups of bulls. The mean benefit in validation reliability of HD genotypes was 0.015 compared with real 50K genotypes and 0.028 compared with 50K samples from HD affected by imputation error and was significant for all traits. The model-based reliability was, on average, 0.036 lower and the regression coefficient was 0.036 closer to the expected value with HD genotypes. The observed gain in validation reliability with HD genotypes was similar to expectations based on the number of markers and the effective number of segregating chromosome segments. Sampling error in the marker-based relationship coefficients causing overestimation of the model-based reliability was smaller with HD genotypes. Inflation of the genomic predictions was reduced with HD genotypes, accordingly. Similar effects on model-based reliability and inflation, but not on the validation reliability, were obtained by shrinkage estimation of the realized relationship matrix from 50K genotypes. PMID- 24210492 TI - Distribution and identification of culturable airborne microorganisms in a Swiss milk processing facility. AB - Airborne communities (mainly bacteria) were sampled and characterized (concentration levels and diversity) at 1 outdoor and 6 indoor sites within a Swiss dairy production facility. Air samples were collected on 2 sampling dates in different seasons, one in February and one in July 2012 using impaction bioaerosol samplers. After cultivation, isolates were identified by mass spectrometry (matrix-assisted laser desorption/ionization-time-of-flight) and molecular (sequencing of 16S rRNA and rpoB genes) methods. In general, total airborne particle loads and total bacterial counts were higher in winter than in summer, but remained constant within each indoor sampling site at both sampling times (February and July). Bacterial numbers were generally very low (<100 cfu/m(3) of air) during the different steps of milk powder production. Elevated bacterial concentrations (with mean values of 391 +/- 142 and 179 +/- 33 cfu/m(3) of air during winter and summer sampling, respectively; n=15) occurred mainly in the "logistics area," where products in closed tins are packed in secondary packaging material and prepared for shipping. However, total bacterial counts at the outdoor site varied, with a 5- to 6-fold higher concentration observed in winter compared with summer. Twenty-five gram-positive and gram-negative genera were identified as part of the airborne microflora, with Bacillus and Staphylococcus being the most frequent genera identified. Overall, the culturable microflora community showed a composition typical and representative for the specific location. Bacterial counts were highly correlated with total airborne particles in the size range 1 to 5 um, indicating that a simple surveillance system based upon counting of airborne particles could be implemented. The data generated in this study could be used to evaluate the effectiveness of the dairy plant's sanitation program and to identify potential sources of airborne contamination, resulting in increased food safety. PMID- 24210493 TI - Microarray-based gene expression profiling of peripheral blood mononuclear cells in dairy cows with experimental hypocalcemia and milk fever. AB - Although a molecular diagnostic assay using clinically accessible tissue, such as blood, would facilitate evaluation of disease conditions in humans and animals, little information exists on microarray-based gene expression profiling of circulating leukocytes from clinically hypocalcemic cows. Therefore, peripheral blood mononuclear cells from dairy cows with experimentally induced hypocalcemia or spontaneous milk fever were subjected to oligo-microarray analysis to identify specific biomarker genes. In experimental hypocalcemia induced by a 4-h infusion of 10% disodium EDTA (n=4), 32 genes were significantly up- or downregulated compared with control treatment (4-h infusion of 11% calcium EDTA; n=4). In cows with milk fever (n=8), 98 genes were expressed differentially (either up- or downregulated) compared with healthy parturient cows (n=5). From these data, the following 5 genes were selected as being strongly related to both experimental hypocalcemia and milk fever: protein kinase (cAMP-dependent, catalytic) inhibitor beta (PKIB); DNA-damage-inducible transcript 4 (DDIT4); period homolog 1 (PER1); NUAK family, SNF1-like kinase, 1 (NUAK1); and expressed sequence tag (BI537947). Another gene (neuroendocrine secretory protein 55, NESP55) was also determined to be specific for milk fever, independently of hypocalcemia. The mRNA expression of these 6 genes in milk fever cases was verified by quantitative real-time reverse transcription PCR and was significantly different compared with their expression in healthy parturient cows. In the present study, the selected genes appeared to be candidate biomarkers of milk fever because the continuous interactions between blood cells and the entire body suggest that subtle intracellular changes occur in association with disease. However, before any genomic biomarkers are incorporated into clinical evaluation of the disease, the effect of hypocalcemia on the mRNA expression of these genes in the tissues that regulate calcium homeostasis in dairy cows should be determined. PMID- 24210494 TI - The effects of heat stress in Italian Holstein dairy cattle. AB - The data set for this study comprised 1,488,474 test-day records for milk, fat, and protein yields and fat and protein percentages from 191,012 first-, second-, and third-parity Holstein cows from 484 farms. Data were collected from 2001 through 2007 and merged with meteorological data from 35 weather stations. A linear model (M1) was used to estimate the effects of the temperature-humidity index (THI) on production traits. Least squares means from M1 were used to detect the THI thresholds for milk production in all parities by using a 2-phase linear regression procedure (M2). A multiple-trait repeatability test-model (M3) was used to estimate variance components for all traits and a dummy regression variable (t) was defined to estimate the production decline caused by heat stress. Additionally, the estimated variance components and M3 were used to estimate traditional and heat-tolerance breeding values (estimated breeding values, EBV) for milk yield and protein percentages at parity 1. An analysis of data (M2) indicated that the daily THI at which milk production started to decline for the 3 parities and traits ranged from 65 to 76. These THI values can be achieved with different temperature/humidity combinations with a range of temperatures from 21 to 36 degrees C and relative humidity values from 5 to 95%. The highest negative effect of THI was observed 4 d before test day over the 3 parities for all traits. The negative effect of THI on production traits indicates that first-parity cows are less sensitive to heat stress than multiparous cows. Over the parities, the general additive genetic variance decreased for protein content and increased for milk yield and fat and protein yield. Additive genetic variance for heat tolerance showed an increase from the first to third parity for milk, protein, and fat yield, and for protein percentage. Genetic correlations between general and heat stress effects were all unfavorable (from -0.24 to -0.56). Three EBV per trait were calculated for each cow and bull (traditional EBV, traditional EBV estimated with the inclusion of THI covariate effect, and heat tolerance EBV) and the rankings of EBV for 283 bulls born after 1985 with at least 50 daughters were compared. When THI was included in the model, the ranking for 17 and 32 bulls changed for milk yield and protein percentage, respectively. The heat tolerance genetic component is not negligible, suggesting that heat tolerance selection should be included in the selection objectives. PMID- 24210495 TI - Consequences of transfer of an in vitro-produced embryo for the dam and resultant calf. AB - No reports exist on consequences of in vitro production (IVP) of embryos for the postnatal development of the calf or on postparturient function of the dam of the calf. Three hypotheses were evaluated: calves born as a result of transfer of an IVP embryo have reduced neonatal survival and altered postnatal growth, fertility, and milk yield compared with artificial insemination (AI) calves; cows giving birth to IVP calves have lower milk yield and fertility and higher incidence of postparturient disease than cows giving birth to AI calves; and the medium used for IVP affects the incidence of developmental abnormalities. In the first experiment, calves were produced by AI using conventional semen or by embryo transfer (ET) using a fresh or vitrified embryo produced in vitro with X sorted semen. Gestation length was longer for cows receiving a vitrified embryo than for cows receiving a fresh embryo or AI. The percentage of dams experiencing calving difficulty was higher for ET than AI. We observed a tendency for incidence of retained placenta to be higher for ET than AI but found no significant effect of treatment on incidence of prolapse or metritis, pregnancy rate at first service, services per conception, or any measured characteristic of milk production in the subsequent lactation. Among Holstein heifers produced by AI or ET, treatment had no effect on birth weight but the variance tended to be greater in the ET groups. More Holstein heifer calves tended to be born dead, died, or were euthanized within the first 20d of life for the ET groups than for AI. Similarly, the proportion of Holstein heifer calves that either died or were culled for poor health after 20d of age was greater for the ET groups than for AI. We observed no effect of ET compared with AI on age at first service or on the percentage of heifers pregnant at first service, calf growth, or milk yield or composition in the first 120d in milk of the first lactation. In a second experiment, embryos were produced using 1 of 2 culture media: synthetic oviductal fluid-bovine embryo 1 (SOF-BE1) or Block-Bonilla-Hansen 7 (BBH7). We detected no difference between cows receiving an SOF-BE1 or BBH7 embryo in gestation length, the percentage of cows in which parturition was induced, or the percentage of cows that experienced calving difficulty, retained placenta, prolapse, or metritis. Among Holstein heifers, birth weight was higher for BBH7 calves than for SOF-BE1 calves. Treatment had no significant effect on calf death. Results indicate that calves born as a result of IVP-ET are more likely to experience alterations in birth weight and increased death in early life but that there were few consequences to the dam of carrying a fetus derived by IVP-ET. PMID- 24210496 TI - Meta-analysis of the effectiveness of the use of triclosan-coated sutures in the prevention of surgical-site infections. PMID- 24210497 TI - Cross-calibration of a GE iDXA and Prodigy for total and regional body bone parameters: the importance of using cross-calibration equations for longitudinal monitoring after a system upgrade. AB - We aimed to determine if cross-calibration equations could be applied to convert GE Lunar Prodigy total and regional bone measurements to the GE iDXA model to support longitudinal monitoring of subjects. The cross-calibration group comprised 63 adults (age 45.1 [12.8] yr; body mass index: 25.6 [3.7] kg/m(2)) and the validation group comprised 25 adults (age 40.5 [11.5] yr; body mass index: 25.7 [3.5] kg/m(2)). The parameters reported were total and regional bone mineral density (BMD), bone mineral content, and bone area. There were significant differences between densitometers for all anatomical regions and reported bone parameters (p < 0.0001); iDXA reported lower BMD than the Prodigy apart from the ribs. Linear regression indicated good agreement for all measurements. Bland Altman analyses indicated significant bias for all measurements and that cross calibration equations were required. The derived cross-calibration equations were effective in reducing differences between predicted and measured results for each parameter and at each region apart from leg BMD, where the difference remained significant (0.013 g/cm(2); p < 0.05). Our results indicate that cross calibration is important to maintain comparability of total body-derived regional bone measurements between the Lunar Prodigy and iDXA. PMID- 24210498 TI - Ligand-targeted liposome design: challenges and fundamental considerations. AB - Nanomedicine, particularly liposomal drug delivery, has expanded considerably over the past few decades, and several liposomal drugs are already providing improved clinical outcomes. Liposomes have now progressed beyond simple, inert drug carriers and can be designed to be highly responsive in vivo, with active targeting, increased stealth, and controlled drug-release properties. Ligand targeted liposomes (LTLs) have the potential to revolutionize the treatment of cancer. However, these highly engineered liposomes generate new problems, such as accelerated clearance from circulation, compromised targeting owing to non specific serum protein binding, and hindered tumor penetration. This article highlights recent challenges facing LTL strategies and describes the advanced design elements used to circumvent them. PMID- 24210499 TI - Cytotoxic compounds from invasive giant salvinia (Salvinia molesta) against human tumor cells. AB - Giant salvinia (Salvinia molesta) is one of the most noxious invasive species in the world. Our bioactivity-guided fractionation of ethanol extract of giant salvinia led to the isolation of 50 compounds. Of the six new compounds (1-6), salviniol (1) is a rare abietane diterpene with a new ferruginol-menthol coupled skeleton and both salviniside I (2) and salviniside II (3) are novel benzofuran glucose conjugates with unique 10-membered macrodiolide structures. Sixteen abietane diterpenes (1, 7-17, and 19-22) demonstrated in vitro activities against human tumor cells, and 7 and 8 showed selective cytotoxicity to tumor cells over normal cells. PMID- 24210500 TI - Anion inhibition studies of a beta-carbonic anhydrase from Clostridium perfringens. AB - A beta-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range of anions such as (thio)cyanate, azide, bicarbonate, nitrate, nitrite, hydrogensulfite, hydrogensulfide, stannate, tellurate, pyrophosphate, divanadate, tetraborate, peroxydisulfate, sulfate, iminodisulfonate and fluorosulfonate. Better inhibitory power, with K(I)s of 0.36-1.0 mM, was observed for cyanide, carbonate, selenate, selenocyanide, trithiocarbonate and diethyldithiocarbamate, whereas the best CpeCA inhibitors were sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, which had KIs in the range of 7-75 MUM. This study thus provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action. PMID- 24210502 TI - Synthesis and methemoglobinemia-inducing properties of analogues of para aminopropiophenone designed as humane rodenticides. AB - A number of structural analogues of the known toxicant para-aminopropiophenone (PAPP) have been prepared and evaluated for their capacity to induce methemoglobinemia--with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed for alkyl analogues of PAPP (aminophenones 1-20; compound 6 metHb% = 74.1 +/- 2). Besides lipophilicity, this structural sub class suggested there were certain structural requirements for activity, with both branched (10-16) and cyclic (17-20) alkyl analogues exhibiting inferior in vitro metHb induction. Of the four candidates (compounds 4, 6, 13 and 23) evaluated in vivo, 4 exhibited the greatest toxicity. In parallel, aminophenone bioisosteres, including oximes 30-32, sulfoxide 33, sulfone 34 and sulfonamides 35-36, were found to be inferior metHb inducers to lead ketone 4. Closer examination of Hammett substituent constants suggests that a particular combination of the field and resonance parameters may be significant with respect to the redox mechanisms behind PAPPs metHb toxicity. PMID- 24210501 TI - Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain. AB - Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza(r)), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study epigenetic regulation and HDAC engagement for drug development for diseases including cancer and psychiatric disorders. 6 ([(18)F]Fluoroacetamido)-1-hexanoicanilide ([(18)F]FAHA) was recently developed as a HDAC substrate and shows moderate blood-brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate- and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [(18)F]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration. PMID- 24210503 TI - New cytotoxic benzosuberene analogs. Synthesis, molecular modeling and biological evaluation. AB - In this Letter we describe the synthesis and biological evaluation of new benzosuberene analogs with structural modifications on the B-ring. The focus was initially to probe the chemical space around the B-ring C-8 position. This position was readily available for derivatization chemistry using our recently developed new synthesis for this compound class. Furthermore, we describe two new B-ring analogs, one containing a diene and the other a cyclic ether group. Both new analogs show excellent potencies in tumor cell proliferation assays. In addition, we describe molecular modeling studies that provide a binding rationale for reference compound 8 in the colchicine binding site using the known colchicine crystal structure. We also examine whether the cell based potency data obtained with selected new analogs are supported by modeling results. PMID- 24210504 TI - Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors. AB - G-protein-coupled receptor kinase (GRK)-2 and -5 are emerging therapeutic targets for the treatment of cardiovascular disease. In our efforts to discover novel small molecules to inhibit GRK-2 and -5, a class of compound based on 3 (benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine was identified as a novel hit by high throughput screening campaign. Structural modification of parent benzoxazole scaffolds by introducing substituents on phenyl displayed potent inhibitory activities toward GRK-2 and -5. PMID- 24210505 TI - Bacterial response to a continuous long-term exposure of silver nanoparticles at sub-ppm silver concentrations in a membrane bioreactor activated sludge system. AB - Silver nanoparticles (nanosilver or AgNPs) have excellent antimicrobial properties. Because of their increasing use, there is a concern about the potential impact of AgNPs in wastewater treatment systems. This study investigated the long-term effects of AgNPs (continuous loading for more than 60 days) on membrane bioreactor (MBR) activated sludge performance. At the influent AgNP concentration of 0.10 mg Ag/L, there was no significant difference in effluent water quality or bacterial activities before and after AgNP exposure. Nitrifying bacterial community structure was relatively stable before and after the long-term AgNP loading. Both ammonia-oxidizing bacteria (AOB) Nitrosomonas spp. and Nitrosospira spp. were present while Nitrospira spp. was the dominant nitrite-oxidizing bacterial species throughout this study. Abundance of silver resistance gene silE in the MBR, however, increased by 50-fold 41 days after the AgNP exposure, and then decreased with continuous AgNP exposure. The long-term nanosilver exposure did not change the membrane fouling rate although extracellular polymeric substances (EPS) concentration increased significantly after nanosilver dosing. The results suggest that AgNPs at the influent concentrations of 0.10 mg/L and below have almost no impact on activated sludge wastewater treatment performance, as activated sludge can effectively reduce nanosilver toxicity by adsorbing or precipitating AgNPs and silver ions (Ag(+)) released from the dissolution of AgNPs. PMID- 24210506 TI - Towards sustainable urban water management: a critical reassessment. AB - Within the literature, concerns have been raised that centralised urban water systems are maladapted to challenges associated with climate change, population growth and other socio-economic and environmental strains. This paper provides a critical assessment of the discourse that surrounds emerging approaches to urban water management and infrastructure provision. As such, 'sustainable urban water management' (SUWM) concepts are scrutinized to highlight the limitations and strengths in the current lines of argument and point towards unaddressed complexities in the transformational agendas advocated by SUWM proponents. Taking an explicit infrastructure view, it is shown that the specific context of the urban water sector means that changes to infrastructure systems occur as an incremental hybridisation process. This process is driven by a range of factors including lock-in effects of legacy solutions, normative values and vested interests of agents, cost and performance certainty and perceptions of risk. Different views of these factors help explain why transformational agendas have not achieved the change SUWM proponents call for and point to the need for a critical reassessment of the system effects and economics of alternative service provision models. PMID- 24210507 TI - Microfiltration of different surface waters with/without coagulation: clear correlations between membrane fouling and hydrophilic biopolymers. AB - Although low-pressure membranes (microfiltration (MF) or ultrafiltration (UF)) have become viable options for drinking water treatment, problems caused by membrane fouling must still be addressed. The objective of this study was to compare five different surface waters and to identify a relevant index of water quality that can be used for prediction of the fouling potential of the water. Bench-scale filtration tests were carried out with commercially available hollow fiber MF membranes. Fairly long-term (a few days) filtrations in the constant flow mode were carried out with automatic backwash. Membrane fouling in this study was shown to be irreversible as a result of the periodic backwash carried out throughout of the operation. Easily accessible indexes of water quality including dissolved organic carbon (DOC), UV absorbance, Ca concentration and turbidity could not explain the degree of fouling encountered in the filtration tests. Fluorescence excitation-emission matrix (EEM) could provide information on the presence of protein-like substances in water, and peaks for protein showed some correlation with the membrane fouling. Biopolymer (characterized by high molecular weights and insensitivity to UV light absorption) concentrations in the five waters determined by liquid chromatography with organic carbon detection (LC OCD) exhibited an excellent correlation with the fouling rates. Coagulation with polyaluminum chloride could mitigate membrane fouling in all cases. The extent of fouling seen with coagulated waters was also correlated with biopolymer concentrations. The relationship between biopolymer concentrations and the fouling rates established for the raw waters could also be applied to the coagulated waters. These results suggested that the contribution of biopolymers to membrane fouling in the present study was significant, an observation that was supported by the analysis of foulants extracted at the termination of each test. Biopolymer concentrations determined by LC-OCD might be used as a key indicator of fouling potential of water for low-pressure membranes. PMID- 24210509 TI - A planning-oriented sustainability assessment framework for peri-urban water management in developing countries. AB - DPSIR and the three-pillar model are well-established frameworks for sustainability assessment. This paper proposes a planning-oriented sustainability assessment framework (POSAF). It is informed by those frameworks but differs insofar as it puts more emphasis on a constructivist conception which recognises that sustainability needs to be defined anew for each planning problem. In finding such a consensus definition, POSAF uses participatory scenario analysis and participatory planning, technical feasibility study, participatory assessment, analysis of trade-offs and social networks in an unusual combination and for goals that differ from the original conceptions of these methods. POSAF was applied in a peri-urban area of Mexico City for the design of improved water service provision, integrating solid waste management. It supported consensus amongst users about the importance of environmental issues, informed planners about the values of stakeholders and users, detected local differences, and identified possible conflicts at an early stage of decision-making. PMID- 24210508 TI - Assessing the impact of transitions from centralised to decentralised water solutions on existing infrastructures--integrated city-scale analysis with VIBe. AB - Traditional urban water management relies on central organised infrastructure, the most important being the drainage network and the water distribution network. To meet upcoming challenges such as climate change, the rapid growth and shrinking of cities and water scarcity, water infrastructure needs to be more flexible, adaptable and sustainable (e.g., sustainable urban drainage systems, SUDS; water sensitive urban design, WSUD; low impact development, LID; best management practice, BMP). The common feature of all solutions is the push from a central solution to a decentralised solution in urban water management. This approach opens up a variety of technical and socio-economic issues, but until now, a comprehensive assessment of the impact has not been made. This absence is most likely attributable to the lack of case studies, and the availability of adequate models is usually limited because of the time- and cost-intensive preparation phase. Thus, the results of the analysis are based on a few cases and can hardly be transferred to other boundary conditions. VIBe (Virtual Infrastructure Benchmarking) is a tool for the stochastic generation of urban water systems at the city scale for case study research. With the generated data sets, an integrated city-scale analysis can be performed. With this approach, we are able to draw conclusions regarding the technical effect of the transition from existing central to decentralised urban water systems. In addition, it is shown how virtual data sets can assist with the model building process. A simple model to predict the shear stress performance due to changes in dry weather flow production is developed and tested. PMID- 24210510 TI - Biodegradation and detoxification potential of rotating biological contactor (RBC) with Irpex lacteus for remediation of dye-containing wastewater. AB - Use of fungal organisms in rotating biological contactors (RBC) for bioremediation of liquid industrial wastes has so far been limited in spite of their significant biodegradation potential. The purpose was to investigate the power of RBC using Irpex lacteus for decolorization and detoxification of industrial dyes and dyeing textile liquors. Recalcitrant dye Methylene Blue (150 mg L(-1)) was decolorized within 70 days, its mutagenicity removed, and the biological toxicity decreased more than 10-fold. I. lacteus biofilm in the RBC completely decolorized within 26 and 47 days dyeing liquors containing disperse or reactive dyes adjusted to pH4.5 and 5-fold diluted with the growth medium, respectively. Their respective biological toxicity values were reduced 10- to 10(4)-fold in dependence of the test used. A battery of toxicity tests comprising Vibrio fisheri, Lemna minor and Sinapis alba was efficient to monitor the toxicity of textile dyes and wastewaters. Strong decolorization and detoxification power of RBC using I. lacteus biofilms was demonstrated. PMID- 24210511 TI - Assessment of wastewater and recycled water quality: a comparison of lines of evidence from in vitro, in vivo and chemical analyses. AB - We investigated water quality at an advanced water reclamation plant and three conventional wastewater treatment plants using an "ecotoxicity toolbox" consisting of three complementary analyses (chemical analysis, in vitro bioanalysis and in situ biological monitoring), with a focus on endocrine disruption. The in vitro bioassays were chosen to provide an appropriately wide coverage of biological effects relevant to managed aquifer recharge and environmental discharge of treated wastewater, and included bioassays for bacterial toxicity (Microtox), genotoxicity (umuC), photosynthesis inhibition (Max-I-PAM) and endocrine effects (E-SCREEN and AR-CALUX). Chemical analysis of hormones and pesticides using LCMSMS was performed in parallel to correlate standard analytical methods with the in vitro assessment. For two plants with surface water discharge into open drains, further field work was carried out to examine in situ effects using mosquitofish (Gambusia holbrooki) as a bioindicator species for possible endocrine effects. The results show considerable cytotoxicity, phytotoxicity, estrogenicity and androgenicity in raw sewage, all of which were significantly reduced by conventional wastewater treatment. No biological response was detected to RO water, suggesting that reverse osmosis is a significant barrier to biologically active compounds. Chemical analysis and in situ monitoring revealed trends consistent with the in vitro results: chemical analysis confirmed the removal trends observed by the bioanalytical tools, and in situ sampling did not reveal any evidence of endocrine disruption specifically due to discharge of treated wastewater (although other sources may be present). Biomarkers of exposure (in vitro) and effect (in vivo or in situ) are complementary and together provide information with a high level of ecological relevance. This study illustrates the utility of combining multiple lines of evidence in the assessment of water quality. PMID- 24210513 TI - Reliability of MEG source imaging of anterior temporal spikes: analysis of an intracranially characterized spike focus. AB - OBJECTIVE: To assess the reliability of MEG source imaging (MSI) of anterior temporal spikes through detailed analysis of the localization and orientation of source solutions obtained for a large number of spikes that were separately confirmed by intracranial EEG to be focally generated within a single, well characterized spike focus. METHODS: MSI was performed on 64 identical right anterior temporal spikes from an anterolateral temporal neocortical spike focus. The effects of different volume conductors (sphere and realistic head model), removal of noise with low frequency filters (LFFs) and averaging multiple spikes were assessed in terms of the reliability of the source solutions. RESULTS: MSI of single spikes resulted in scattered dipole source solutions that showed reasonable reliability for localization at the lobar level, but only for solutions with a goodness-of-fit exceeding 80% using a LFF of 3 Hz. Reliability at a finer level of intralobar localization was limited. Spike averaging significantly improved the reliability of source solutions and averaging 8 or more spikes reduced dependency on goodness-of-fit and data filtering. CONCLUSIONS: MSI performed on topographically identical individual spikes from an intracranially defined classical anterior temporal lobe spike focus was limited by low reliability (i.e., scattered source solutions) in terms of fine, sublobar localization within the ipsilateral temporal lobe. Spike averaging significantly improved reliability. SIGNIFICANCE: MSI performed on individual anterior temporal spikes is limited by low reliability. Reduction of background noise through spike averaging significantly improves the reliability of MSI solutions. PMID- 24210512 TI - Variability of peak shoulder force during wheelchair propulsion in manual wheelchair users with and without shoulder pain. AB - BACKGROUND: Manual wheelchair users report a high prevalence of shoulder pain. Growing evidence shows that variability in forces applied to biological tissue is related to musculoskeletal pain. The purpose of this study was to examine the variability of forces acting on the shoulder during wheelchair propulsion as a function of shoulder pain. METHODS: Twenty-four manual wheelchair users (13 with pain, 11 without pain) participated in the investigation. Kinetic and kinematic data of wheelchair propulsion were recorded for 3 min maintaining a constant speed at three distinct propulsion speeds (fast speed of 1.1 m/s, a self-selected speed, and a slow speed of 0.7 m/s). Peak resultant shoulder forces in the push phase were calculated using inverse dynamics. Within individual variability was quantified as the coefficient of variation of cycle to cycle peak resultant forces. FINDINGS: There was no difference in mean peak shoulder resultant force between groups. The pain group had significantly smaller variability of peak resultant force than the no pain group (P<0.01, eta2=0.18). INTERPRETATION: The observations raise the possibility that propulsion variability could be a novel marker of upper limb pain in manual wheelchair users. PMID- 24210514 TI - Transcranial pulsed current stimulation: a new way forward? PMID- 24210515 TI - Reply to "Using relative frequency estimation of transcranial magnetic stimulation motor threshold does not allow to draw any conclusions about true threshold". PMID- 24210516 TI - EEG source imaging of anterior temporal lobe spikes: validity and reliability. AB - OBJECTIVE: To assess the reliability and validity of EEG source localization of anterior temporal lobe spikes through direct comparison with simultaneously recorded intracranial spike fields. METHODS: We recently showed that classical anterior temporal spikes recorded in mesial temporal lobe epilepsy (MTLE) are non propagated potentials generated in the anterolateral temporal neocortex (Wennberg et al., 2011). In this study EEG source imaging (ESI) was performed on 64 identical right anterior temporal spikes (and 48 homologous left anterior temporal spikes) in a patient with MTLE investigated with simultaneous depth and subdural intracranial EEG and 27 channel scalp EEG. The effects of different realistic forward models, low frequency filters (LFFs) and spike averaging were assessed in terms of the reliability and physiologic validity of the source solutions. RESULTS: Dipole mapping and distributed source modeling solutions for the grand average of all spikes were accurately localized to the superficial anterolateral temporal neocortex within 1cm of the intracranially defined spike generator, irrespective of forward model or LFF. ESI of single spikes, however, showed poor reliability (i.e., dissimilar localization results for intracranially identical spikes). Even with an optimal combination of individualized volume conductor and 3Hz LFF more than one third of single spike source solutions were physiologically invalid. Spike averaging, especially of 8 or more spikes, significantly increased the proportion of valid source solutions. CONCLUSIONS: ESI of individual anterior temporal spikes was limited by low reliability and a high likelihood of physiologically invalid source solutions. Spike averaging of 8 or more identical spikes prior to ESI, however, reliably produced accurate source solutions localized to the anterolateral temporal neocortex. SIGNIFICANCE: ESI performed on averages of identical spikes can provide highly accurate noninvasive source localization of the anterolateral temporal neocortical region responsible for generating classical anterior temporal lobe spikes. The reliability and validity of ESI performed on individual spikes, however, is relatively limited. PMID- 24210517 TI - Agreement in participant-coded and investigator-coded food-record analysis in overweight research participants: an examination of interpretation bias. AB - Validation studies support the use of self-administered computerized methods for reporting energy intake; however, the degree of interpretation bias with these methods is unknown. This research compared nutrient intake for food records that were both participant coded (using the National Cancer Institute's Automated Self Administered 24-hour recall [ASA24] online program) and investigator-coded (a single investigator coded all food records using the ESHA Food Processor diet analysis program). Participants (n=28; mean age=41+/-11 years; mean body mass index=31+/-6) were participants in an 8-week trial (conducted between March 2011 and June 2011 in Phoenix, AZ) investigating the impact of meal preloads on satiety. Food records were collected on four occasions during the trial and, of the food records available for this investigation (n=161), 88% were completed on a weekday. Intra-class correlation coefficients were computed for selected nutrients and ranged from 0.65 to 0.81 for the macronutrients and from 0.50 to 0.66 for the micronutrients (overall mean=0.67). Overall mean coefficient improved to 0.77 when the data from three or more food records per participant were averaged, as is commonly done in nutrition research. All intra-class correlation coefficients were significant (P<0.020) and were not impacted by the day of week that food was recorded. For energy, macronutrients, and minerals, the percent median differences between coders were <+/-17%; however, percent median differences were large for vitamin C (+27%) and beta carotene (+294%). Findings from this study suggest that self-administered dietary assessment has merit as a research tool. Pretrial training for research participants is suggested to reduce interpretation bias. PMID- 24210518 TI - [Contribution of family physicians in the development of clinical practice guidelines]. PMID- 24210519 TI - [Perceived satisfaction and usefulness of suicide prevention information for patients and relatives]. AB - OBJECTIVE: To assess the satisfaction of persons with suicidal behaviour and their relatives using patient information material included in the Clinical Practice Guidelines on Prevention and Treatment of Suicidal Behaviour. METHOD: The sample was made up of 57 patients with suicidal ideation or behaviour, and 52 relatives. The participants were recruited through a suicide prevention programme (Programa de intervencion intensiva en conducta suicida [PII] - Suicidal Behaviour Intensive Intervention Programme) and a family association (Federacion de Asociaciones de Familiares y Personas con enfermedad mental de Galicia [FEAFES] - Galician Federation of Associations of Relatives and Persons with mental diseases). An ad-hoc questionnaire was designed to ascertain the degree of perceived satisfaction and usefulness of using the information included in the guidelines. RESULTS: The descriptive data of the sample is presented, along with an exploratory factorial analysis of the questionnaire that yielded two dimensions, i.e., format and usefulness. Patients scored significantly lower than the relatives in two dimensions; nevertheless, no significant differences were found between the two groups in the level of general satisfaction. The socio demographic variables did not influence the results. Similarly, no differences were observed between patients with and without history of suicidal behaviour. Participants stressed that Primary Care was the setting best suited for dissemination of this type of information. CONCLUSIONS: In general, both patients and relatives displayed a high level of satisfaction with the patient information material assessed. Furnishing information of this type to patients with suicidal ideation and/or behaviour could act as a preventive-educational tool. PMID- 24210520 TI - [Easily implemented cognitive behaviour techniques in primary care (part 2)]. AB - Cognitive behavioural therapy has shown to be very effective for treating the vast majority of mental health disorders. In this second part of the article, we continue commenting on those techniques that can be easily used in the Primary Care setting. PMID- 24210521 TI - [Use of glucose-lowering drugs in a primary care setting in Malaga during the years 2008-2012]. AB - INTRODUCTION: The aim of the study is to describe the pattern of use of hypoglycemic agents in a primary health care district of Malaga between the years 2008-2012. MATERIAL AND METHOD: Cross-sectional descriptive study. Malaga health district. Population of 609,781 inhabitants; 42,060 people in the diabetes process. Therapeutic sub-group A10 (drugs used in diabetes). Data is presented as defined daily dose (DDD). Years 2008-2012. Measures of frequency. RESULTS: The population grew by 0.4% and the people included in the diabetes process, by 19%. The hypoglycemic agents have increased from 12,453,443 to 14,144,817 DDD (13.5%). Oral antidiabetics increased by 13.8% and insulin by 9.7%. Metformin is the most used oral antidiabetic (6,655,923 DDD) and the iDDP4 was the one that had increased more (from 63,882 DDD to 1,482,574). The growth in insulin use was mainly due to the long-acting (38%) and the shorter-acting one (40%). The most used insulin doses are the long-acting ones, followed by the pre-mixed. The proportion of insulin use as regards the use of ADOs has remained stable (31%)., Long-acting (36%) insulin has become the most used, followed by pre-mixed (34%), shorter-acting (16%), and the intermediate-acting (12%). CONCLUSIONS: There is an increase in the use of hypoglycemic agents., Metformin and iDPP4 are the antidiabetics oral with the greatest growth., There is an increase in shorter acting and long-acting insulins with a decrease in intermediate-acting and pre mixed., The proportion of oral antidiabetics/insulins has remained stable. PMID- 24210522 TI - [Comorbidity of migraine and psychiatric disorders]. PMID- 24210523 TI - [Is chest pain a rare manifestation of Brugada syndrome?]. PMID- 24210524 TI - Improving results of autologous stem cell transplantation for Philadelphia positive acute lymphoblastic leukaemia in the era of tyrosine kinase inhibitors: a report from the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. AB - BACKGROUND: Outcome of Philadelphia-positive acute lymphoblastic leukaemia (Ph+ ALL) improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). Autologous stem cell transplantation (ASCT) has never been considered a standard of care in this setting. The aim of our study was to analyse if results of ASCT improved in the era of TKIs. PATIENTS AND METHODS: One-hundred and seventy-seven adults with Ph+ ALL treated with ASCT in first complete remission were analysed for the impact of year of transplantation on outcome. Additional analysis was performed including 32 patients for whom detailed data on the use of TKIs and the status of minimal residual disease were collected. RESULTS: The probability of the overall survival (OS) at 3 years increased from 16% for transplants performed between 1996 and 2001 to 48% between 2002 and 2006 and 57% between 2007 and 2010 (P<.0001). Leukaemia-free survival (LFS) was 11%, 39% and 52%, respectively (P<.0001). Relapse incidence decreased from 70% to 45% and 45% (P=.01), respectively, while non-relapse mortality was 19%, 15% and 3% (P=.08). In a multivariate analysis, year of ASCT was the only independent factor influencing the risk of treatment failure (hazard ratio (HR)=0.37; P<.001). In a subgroup of 22 patients actually treated with TKIs and being in complete molecular remission at the time of ASCT, the LFS rate at 3 years was 65%. CONCLUSIONS: Results of ASCT for Ph+ ALL improved significantly over time. Prospective, innovative studies are needed to verify the role of ASCT in this patient setting. PMID- 24210525 TI - Blood-feeding patterns of horse flies in the French Pyrenees. AB - Horse flies can mechanically transmit Besnoitia besnoiti, the agent of bovine besnoitiosis. Although previously limited to enzootic areas, especially the French Pyrenees Mountains, bovine besnoitiosis is now considered a re-emerging disease in western Europe. To improve understanding of the role of horse flies as mechanical vectors, this study investigated their blood-feeding ecology in the eastern French Pyrenees, in two high-altitude summer pastures whose main domestic ungulates were cattle, and in a wildlife park with native fauna. Species-specific PCR assays were conducted to identify the sources of blood meals: wild boar, horse, cattle (or bison), sheep (or mouflon), goat, red deer, roe deer and izard (or Pyrenean chamois). In La Mouline pasture, tabanids (N=20) fed on red deer (70%) and cattle (30%). In Mantet pasture, tabanids (N=24) fed on cattle (52%), red deer (20%), wild boar (16%), horse (8%) and sheep (4%). In the wildlife park, Tabanus bromius (N=32), the most abundant species collected, fed on red deer (85%), bison (9%) and wild boar (6%). Despite relatively high densities in both the pastures and in the wildlife park, small wild ungulates (izard, mouflon and roe deer) were not detected as a source of blood meals. Only two mixed blood meals were identified in two specimens of T. bromius: cattle/horse for the specimen collected in the pastures, and bison/wild boar for the specimen collected in the wildlife park. Our findings showed that tabanids display a level of opportunistic feeding behaviour, in addition to a preference for red deer, the latter being particularly true for Philipomyia aprica, the most abundant species collected in the pastures. PMID- 24210526 TI - Regional atrophy is associated with impairment in distinct cognitive domains in Alzheimer's disease. AB - BACKGROUND: In Alzheimer's disease (AD), some patients present with cognitive impairment other than episodic memory disturbances. We evaluated whether occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) could account for differences in cognitive domains affected. METHODS: In 329 patients with AD, we assessed five cognitive domains: memory, language, visuospatial functioning, executive functioning, and attention. Magnetic resonance imaging (MRI) was rated visually for the presence of MTA and PA. Two-way analyses of variance were performed with MTA and PA as independent variables, and cognitive domains as dependent variables. Gender, age, and education were covariates. As PA is often encountered in younger patients, analyses were repeated after stratification for age of onset (early onset, <=65 years). RESULTS: The mean age of the participants was 67 years, 175 (53%) were female, and the mean Mini-Mental State Examination (score+/-standard deviation) was 20+/-5 points. Based on dichotomized magnetic resonance imaging ratings, 84 patients (26%) had MTA and PA, 98 (30%) had MTA, 57 (17%) had PA, and 90 (27%) had neither. MTA was associated with worse performance on memory, language, and attention (all, P<.05), and PA was associated with worse performance on visuospatial and executive functioning (both, P<.05). Stratification for age showed in patients with late-onset AD (n=173) associations between MTA and impairment on memory, language, visuospatial functioning, and attention (all, P<.05); in early-onset AD (n=156), patients with PA tended to perform worse on visuospatial functioning. CONCLUSIONS: Regional atrophy is related to impairment in specific cognitive domains in AD. The prevalence of PA in a large set of patients with AD and its association with cognitive functioning provides support for the usefulness of this visual rating scale in the diagnostic evaluation of AD. PMID- 24210527 TI - Aging children of long-lived parents experience slower cognitive decline. AB - BACKGROUND: Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. METHODS: Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. RESULTS: Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12 72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. CONCLUSIONS: Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging. PMID- 24210528 TI - Verbal communication disorders in brain damaged post-stroke patients in Benin. AB - In Western countries, progress has lessened the severity of numerous sequels of verbal communication disorders (VCD). For Africa and more particularly Benin, few data on the subject are presently available. OBJECTIVE: To analyze the occurrence and development of post-stroke VCD in Benin. METHOD: A retrospective, descriptive and analytical study focused on 563 post-stroke patients treated in rehabilitation department of the National university hospital of Cotonou (CNHU) from January 2006 through December 2010. RESULTS: VCD prevalence was 42.10%. Average age was 57.17 +/- 12.62 years, sex ratio was 1.75, and 74.69% were right handed. VCD affected oral expression (95.78%), written expression (2.11%), oral comprehension (13.08%) and written comprehension or reading (0.84%). Type of stroke, sex and age had no impact on VCD occurrence following stroke. Only 5.91% of the patients underwent speech therapy. Progression was favorable in 21.09% of the cases studied. CONCLUSION: In Benin, post-stroke VCD is exceedingly common and occasions major social difficulties. Prevalence of VCD in a predominantly oral culture underscores the need for speech therapists to develop a more broadly ecological approach toward treatment. PMID- 24210529 TI - Premorbid teacher-rated social functioning predicts adult schizophrenia-spectrum disorder: a high-risk prospective investigation. AB - Social functioning deficits are a core component of schizophrenia spectrum disorders, and may emerge years prior to the onset of diagnosable illness. The current study prospectively examines the relation between teacher-rated childhood social dysfunction and later mental illness among participants who were at genetic high-risk for schizophrenia and controls (n=244). The teacher-rated social functioning scale significantly predicted psychiatric outcomes (schizophrenia-spectrum vs. other psychiatric disorder vs. no mental illness). Poor premorbid social functioning appears to constitute a marker of illness vulnerability and may also function as a chronic stressor potentially exacerbating risk for illness. PMID- 24210530 TI - Using negative feedback to guide behavior: impairments on the first 4 cards of the Wisconsin Card Sorting Test predict negative symptoms of schizophrenia. AB - Research has demonstrated that individuals with schizophrenia fail to appropriately use negative feedback to guide learning. These learning deficits are thought to arise from abnormalities in midbrain dopamine activity. Primary and enduring negative symptoms are also associated with abnormal dopamine activity and are expected to produce more severe deficits in learning when they present in individuals with schizophrenia. The current study examines this matter by comparing individuals with deficit syndrome schizophrenia, which is characterized by primary and enduring negative symptoms, to individuals with nondeficit syndrome schizophrenia and to normal controls in their use of positive feedback and negative feedback to guide learning on the first four cards of the WCST. Participants included 67 individuals with schizophrenia (15 deficit; 52 nondeficit syndrome) and 51 healthy controls. Accuracy data from the first 4 cards of the WCST and measures of global test performance were examined. Individuals with schizophrenia were significantly less accurate than controls in their performance on early (pre-shift) WCST trials, and this impairment was significantly greater in patients with deficit than nondeficit schizophrenia. Additionally, accuracy across the first 4 WCST cards significantly predicted the number of categories completed and percentage of perseverative errors across the entire test. These findings suggest that negative symptoms of schizophrenia are associated with difficulty using negative feedback to adaptively guide behavior, and are consistent with the notion that abnormal DA signaling contributes to the higher-order executive functioning impairments seen in schizophrenia with severe negative symptoms. PMID- 24210531 TI - Differential regulation of schizophrenia-associated microRNA gene function by variable number tandem repeats (VNTR) polymorphism. PMID- 24210532 TI - From methadone to buprenorphine: changes during a 10 year period within a national opioid maintenance treatment programme. AB - Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. Maintenance programmes differ in various aspects and may also change over time. This paper investigates the changes in treatment practices within a national OMT programme during a 10 year period (2002-2011), especially with regard to the prescribing of methadone and buprenorphine. Data (n=34,001) were collected by annual assessments questionnaires. In 2002, only 16% of the OMT patients received buprenorphine as their maintenance medication. By 2011 this percentage had increased significantly (p<.001) to 50.3%. In the same period the number of patients more than tripled (from 1,984 to 6,640, p<.001), and programme attrition rates decreased (p=.020). This relatively rapid shift is a part of the increasing reliance of addiction medicine upon a range of medications administered by different routes which has not been previously charted within a national treatment programme. PMID- 24210533 TI - Motivational interviewing versus brief advice for cigarette smokers in residential alcohol treatment. AB - Residential treatment for substance use disorders (SUD) provides opportunity for smoking intervention. A randomized controlled trial compared: (1) motivational interviewing (MI) to brief advice (BA), (2) in one session or with two booster sessions, for 165 alcoholics in SUD treatment. All received nicotine replacement (NRT). MI and BA produced equivalent confirmed abstinence, averaging 10% at 1 month, and 2% at 3, 6 and 12 months. However, patients with more drug use pretreatment (>22 days in 6 months) given BA had more abstinence at 12 months (7%) than patients in MI or with less drug use (all 0%). Boosters produced 16-31% fewer cigarettes per day after BA than MI. Substance use was unaffected by treatment condition or smoking cessation. Motivation to quit was higher after BA than MI. Thus, BA plus NRT may be a cost-effective way to reduce smoking for alcoholics with comorbid substance use who are not seeking smoking cessation. PMID- 24210534 TI - Randomized controlled trial of MICBT for co-existing alcohol misuse and depression: outcomes to 36-months. AB - Integrated psychological treatment addressing co-existing alcohol misuse and depression has not been compared with single-focused treatment. This trial evaluates changes over 36 months following randomization of 284 outpatients to one of four motivational interviewing and cognitive-behavior therapy (MICBT) based interventions: (1) brief integrated intervention (BI); or BI plus 9 further sessions with (2) an integrated-, (3) alcohol-, or (4) depression-focus. Outcome measures included changes in alcohol consumption, depression (BDI-II: Beck Depression Inventory) and functioning (GAF: Global Assessment of Functioning), with average improvements from baseline of 21.8 drinks per week, 12.6 BDI-II units and 8.2 GAF units. Longer interventions tended to be more effective in reducing depression and improving functioning in the long-term, and in improving alcohol consumption in the short-term. Integrated treatment was at least as good as single-focused MICBT. Alcohol-focused treatment was as effective as depression focused treatment at reducing depression and more effective in reducing alcohol misuse. The best approach seems to be an initial focus on both conditions followed by additional integrated- or alcohol-focused sessions. PMID- 24210535 TI - Left nutcracker syndrome and right ureteropelvic junction obstruction. AB - We report a rare case of left nutcracker syndrome and right ureteropelvic junction obstruction in a young woman who suffered flank pain and hematuria. The diagnosis was confirmed with the help of Doppler ultrasonography, retrograde pyelography, magnetic resonance angiography, and magnetic resonance urography. A surgery that involves left renal vein decompression and dismembered Anderson Hynes pelvioplasty was performed. The patient was followed up for 23 months, and her symptoms were relieved. PMID- 24210536 TI - Robotic single port cholecystectomy (R-LESS-C): experience in 36 patients. AB - BACKGROUND: Laparoendoscopic single-site surgery (LESS) has emerged as a result of a search for "pain-less" and "scar-less" surgery. Laparoendoscopic single-site cholecystectomy (LESS-C) is probably the most common application in general surgery, although it harbors certain limitations. It was proposed that the da Vinci Single-Site (Si) robotic system may overcome some of the difficulties experienced during LESS, providing three dimensional views and the ability to work in a right-handed fashion. Thirty-six robotic single port cholecystectomies (R-LESS-C) performed with the da Vinci Si robotic system are evaluated in this paper MATERIALS AND METHODS: R-LESS-C performed in 36 patients were reviewed. The data related to the perioperative period (i.e., anesthesia time, operation time, docking time, and console time) was recorded prospectively, whereas the hospitalization period, postoperative visual analogue scale (VAS) pain scores were collected retrospectively. RESULTS: A total number of 36 patients, with a mean age of 40.1 years (21-64 years), underwent R-LESS-C. There were five men and 31 women. The mean anesthesia and operation times were 79.3 minutes (45-130 minutes) and 61.8 minutes (34-110 minutes), respectively. The mean docking time was 9.8 minutes (4-30 minutes) and the mean console time was 24.9 minutes (7-60 minutes). The mean hospital stay was 1.05 days (1-2 days) and the mean pain score (VAS) was 3.6 (2-8) in the first 24 hours. Incisional hernia was recorded in one patient. CONCLUSION: R-LESS-C can be performed reliably with acceptable operative times and safety. The da Vinci Si robotic system may ease LESS-C. Two issues should be considered for routine use: expensive resources are needed and the incidence of incisional hernia may increase. PMID- 24210537 TI - Challenges in the management of massive intraorbital and hemifacial arteriovenous malformation as causing life-threatening epistaxis. AB - Arteriovenous malformations are congenital lesions that may evolve with time and manifest in a plethora of presentations. They can occur as torrential epistaxis when it extensively involves the facial region. Multi-imaging modalities are available to assist in characterizing the structure of the lesion as well as its location and extent. This complex disease requires a multidisciplinary team approach with preoperative embolization and surgery. We present a rare cause of life-threatening epistaxis in a gentleman with a longstanding orbital and hemifacial arteriovenous malformation and discuss the complexities involved in its management. PMID- 24210538 TI - Antegrade repositioning of Memokath stent in malignant ureteroileal anastomotic stricture. AB - Ureteric strictures are common and can be due to benign or malignant causes. Various surgical treatments can be used from minimally invasive endoscopic retrograde JJ stent insertion, balloon dilatation, ureterolithotomy, to open surgical exploration and repair. Memokath 051 stent is a metallic stent designed for long-term ureteral stenting in the management of ureteral strictures. The insertion of this device is usually a straightforward procedure performed endoscopically in a retrograde fashion via cystoscopy. However, this procedure can be difficult in complicated scenarios when the bladder has been removed with neoureteral reimplantations or high-grade strictures. Here, we report a case of Memokath stent insertion complicated by placement difficulties in a lady with ileal conduit due to previous ovarian cancer complicated by vesicovaginal fistula, who presented with malignant stricture of the ureteroileal anastomosis. We describe a simple yet effective antegrade technique to precisely reposition the malpositioned Memokath stent, along with illustrations. PMID- 24210539 TI - Surgical treatment of catamenial pneumothorax: Report of three cases. AB - Catamenial pneumothorax (CP) is a rare entity of spontaneous, recurring pneumothorax in females. Although it has been known to be associated with thoracic endometriosis, varying clinical course and the lack of consistent intraoperative findings have led to conflicting etiological theories. We herein discuss the etiology, clinical course, and surgical treatment of three patients with CP. Three females (aged 40 years, 28 years, and 34 years) had recurrent right-sided spontaneous pneumothoraces that coincided with their menses. They had undergone video-assisted thoracoscopic surgery (VATS) previously. Blueberry spots in the right diaphragm were detected in all three cases. Two patients had recurrence, postoperatively. The other patient, who received luteinizing hormone releasing hormone analog therapy for an abdominal endometriosis in the perioperative period and postoperative chemical pleurodesis to prevent recurrence, has been free of recurrence for 15 months, postoperatively. However, pelvic endometriosis was detected in this patient only. Therefore, CP should be suspected in ovulating females with spontaneous pneumothorax, even in the absence of any symptoms associated with pelvic endometriosis. In addition, while performing VATS, careful inspection of the diaphragmatic surface is important. In complicated cases, hormonal suppression therapy and chemical pleurodesis might also be helpful adjunct modalities. PMID- 24210540 TI - Morbidity- and mortality-related prognostic factors of nontraumatic splenectomies. AB - BACKGROUND: Splenectomy is a common surgical procedure, but few reports focus on nontraumatic splenectomies. The aim of this study was to determine the predictors of morbidity and mortality of patients submitted to elective nontraumatic splenectomy. METHODS: A descriptive cross-sectional study of 152 consecutive, nonselected, nontraumatic patients operated on by splenectomy between 1996 and 2010 was carried out. Clinical, laboratory, and surgical data, histological findings, perioperative mortality, and postoperative complications according to Clavien-Dindo classification, were recorded. Factors related to morbidity and mortality were analyzed. RESULTS: Of the 152 patients (89 male and 63 female; mean age 49.8 +/- 17.8 years), 74 (48.7%) were operated on for malignant hematologic disorders, 44 for benign hematologic process, and 34 for other nonhematologic disorders. The spleen was enlarged in 95 patients (62.5%) and 78 patients (51.3%) had hypersplenism. The overall complications rate was 40.1%: Grades I and II in 27 cases (17.7%), and Grades III and IV in 23 patients (15.1%). Perioperative mortality was 7.2% (11 patients). In univariate analysis, significant negative predictors for morbidity were age (p = 0.004), anemia (p = 0.03), leukocytosis (p = 0.016), and blood transfusions (p < 0.001). In the multivariate analysis, only the need for blood transfusion remained as an independent prognostic factor (p = 0.001). Related to mortality, negative prognostic factors were age (p = 0.003), leukocytosis (p = 0.048), American Society of Anesthesiologists (ASA) score (p < 0.001), blood transfusion (p < 0.001), pleural effusion (p = 0.031), and pneumonia (p = 0.001). Pneumonia remained an independent prognostic factor of mortality (p = 0.024). CONCLUSION: Blood loss is the most important prognostic factor for postoperative complications after nontraumatic splenectomies. Pneumonia is the main prognosis factor for perioperative mortality. PMID- 24210541 TI - Incretin levels 1 month after laparoscopic single anastomosis gastric bypass surgery in non-morbid obese type 2 diabetes patients. AB - PURPOSE: Bariatric surgery is an efficient procedure for the remission of type 2 diabetes (T2DM) from morbid obesity. However, in Asian countries, the mean body mass index (BMI) of T2DM patients is about 25 kg/m(2). Various data on patients undergoing gastric bypass surgery suggest that the control of T2DM after surgery occurs rapidly. We hypothesized that even in nonobese patients with T2DM, the levels of incretin and insulin changed along with the improvement of T2DM as a consequence of the gastric bypass. MATERIALS AND METHODS: From March to December 2011, 12 nonobese patients (mean BMI; 26.2 kg/m(2)) with poorly-controlled [mean glycated hemoglobin (HbA1C); 9.5%] diabetes underwent gastric bypass surgery. Values related to diabetes, including incretin [gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1)] levels were measured before and 1 month after surgery. All values were measured in response to a 75 g oral glucose tolerance test (OGTT). RESULTS: On average, the BMI decreased by 2.1 +/- 0.7 kg/m(2). Mean HbA1C level decreased by 1.6 +/- 2%. Oral glucose-stimulated insulin levels increased and GLP-1 levels also increased significantly. Oral glucose-stimulated GIP levels decreased sharply. CONCLUSION: Soon after gastric bypass in nonobese T2DM patients, control of T2DM is achieved. The incretin release after oral glucose is improved. This could be a consequence of changes of the enteroinsular axis, particularly in the incretins. PMID- 24210542 TI - Inflammatory myofibroblastic tumors of the duodenum. AB - Inflammatory myofibroblastic tumors (IMTs) are rare soft-tissue tumors that can occur at virtually any anatomical site. We report the case of a 58-year-old male with an IMT of the fourth part of the duodenum who presented with signs and symptoms of high intestinal obstruction and bilious vomiting. The patient underwent a surgical resection of the fourth part of the duodenum with end-to-end duodenojejunal anastomosis. The follow-up period of 6 months was uneventful with no evidence of recurrence. According to our knowledge, only six cases of duodenal IMTs have been reported in the literature thus far, and this is the first report of a duodenal IMT sited at the fourth part of the duodenum. The duodenum is among the rarest sites of IMTs. Signs and symptoms resulting from diagnostic imaging investigations are nonspecific and inadequate to obtain diagnosis accurately. In most cases, surgical treatment is considered a cure for IMTs. There is no evidence of deaths caused by duodenal IMT. IMT of the duodenum is a possible diagnosis in differential diagnosis of tumor-like lesions of the duodenum. PMID- 24210543 TI - High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer. AB - BACKGROUND: Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC). METHODS: EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. RESULTS: High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P = .028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P = .0004). A significant association was shown between EGFR and IGF1R protein overexpression (P < .005). Patients with high expression of both receptors had a poorer overall survival (OS) (P = .04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P = .0004 and P = .0009), with SCC having higher expression levels than ADC. CONCLUSION: Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. PMID- 24210544 TI - Anti-estrogenic activity formation potential assessment and precursor analysis in reclaimed water during chlorination. AB - Chlorination was reported to increase the anti-estrogenic activity in reclaimed water from domestic wastewater treatment plants, which may add to the risk of reclaimed water reuse. In order to assess the anti-estrogenic disinfection by product (DBP) precursors, the anti-estrogenic activity formation potential (AEAFP) during chlorination was studied. Firstly, the conditions for the experimental measurement of AEAFP were determined. A 24-h chlorination experiment was applied for AEAFP measurement. After chlorination, dechlorination using reductive reagents led to significant loss of anti-estrogenic activity formation. In addition, as the presence of ammonia nitrogen and other major chlorine consumers would result in lower anti-estrogenic activity formation, a basic chlorine dose of 3* DOC (mg-Cl2 L(-1)) was adequate for completely transforming the anti-estrogenic DBP precursors while an extra chlorine dose of 8* ammonia nitrogen + 5* nitrite-nitrogen (mg-Cl2 L(-1)) should be added when there was a high level of ammonia nitrogen and nitrite nitrogen in the reclaimed water. Therefore, 24-h chlorination without dechlorination or using only non-reductive quenching reagents (e.g. ammonium) for dechlorination and a total chlorine dose of 3* DOC + 8* ammonia nitrogen + 5* nitrite nitrogen (mg-Cl2 L(-1)) should be fulfilled for the AEAFP measurement. Moreover, the AEAFP (0.2-2.1 mg-TAM L(-1)) of the reclaimed water samples (n = 20) were further analyzed. The AEAFP was highly correlated to UV254 and the fluorescence volume in excitation emission matrix fluorescence spectrum which can be used as surrogates to indicate the level of the AEAFP and assess the precursors in reclaimed water. PMID- 24210545 TI - Assessment of pH shock as a method for controlling sulfide and methane formation in pressure main sewer systems. AB - Caustic dosing to raise pH above 10.0 for short periods (hours) is often used by water utilities for controlling sulfide formation in sewers. However the effectiveness of this strategy is rarely reported and the impact of pH level and exposure time on the effectiveness is largely unknown. The effectiveness of this strategy under various pH levels (10.5-12.5) and exposure time (0.5-6.0 h) in controlling sulfide and methane production was evaluated in laboratory scale anaerobic sewer reactors and then in a real sewer system. Laboratory studies showed that the sulfide production rate of the laboratory sewer biofilm was reduced by 70-90% upon the completion of the pH shock, while the methane production rate decreased by 95-100%. It took approximately one week for the sulfate-reducing activity to recover to normal levels. In comparison, the methanogenic activities recovered to only about 10% in 4 weeks. The slow recovery is explained by the substantially loss of cell viability upon pH shocks, which recovered slowly after the shocks. Laboratory studies further revealed that a pH level of 10.5 for 1-2 h represent cost-effective conditions for the pH shock treatment. However, field trials showed a higher pH (11.5) and larger dosing times are needed due to the pH decreases along the sewer line and at the two ends of the caustic-receiving wastewater slugs due to dilution. To have effective sulfide and methane control, it is important to ensure effective conditions (pH > 10.5 and duration >1-2 h) for the entire sewer line. PMID- 24210546 TI - Identification and characterization of metabolic properties of bacterial populations recovered from arsenic contaminated ground water of North East India (Assam). AB - Diversity of culturable bacterial populations within the Arsenic (As) contaminated groundwater of North Eastern state (Assam) of India is studied. From nine As contaminated samples 89 bacterial strains are isolated. 16S rRNA gene sequence analysis reveals predominance of Brevundimonas (35%) and Acidovorax (23%) along with Acinetobacter (10%), Pseudomonas (9%) and relatively less abundant (<5%) Undibacterium, Herbaspirillum, Rhodococcus, Staphylococcus, Bosea, Bacillus, Ralstonia, Caulobacter and Rhizobiales members. High As(III) resistance (MTC 10-50 mM) is observed for the isolates obtained from As(III) enrichment, particularly for 3 isolates of genus Brevundimonas (MTC 50 mM). In contrast, high resistance to As(V) (MTC as high as 550 mM) is present as a ubiquitous property, irrespective of isolates' enrichment condition. Bacterial genera affiliated to other groups showed relatively lower degree of As resistance [MTCs of 15-20 mM As(III) and 250-350 mM As(V)]. As(V) reductase activity is detected in strains with high As(V) as well as As(III) resistance. A strong correlation could be established among isolates capable of reductase activity and siderophore production as well as As(III) tolerance. A large number of isolates (nearly 50%) is capable of anaerobic respiration using alternate inorganic electron acceptors [As(V), Se(VI), Fe(III), [NO(3)(2), SO(4)(2), S(2)O(3)(2). Ability to utilize different carbon sources ranging from C2-C6 compounds along with some complex sugars is also observed. Particularly, a number of strains is found to possess ability to grow chemolithotrophically using As(III) as the electron donor. The study reports for the first time the identity and metabolic abilities of bacteria in As contaminated ground water of North East India, useful to elucidate the microbial role in influencing mobilization of As in the region. PMID- 24210547 TI - Metabolic versatility in full-scale wastewater treatment plants performing enhanced biological phosphorus removal. AB - This study analysed the enhanced biological phosphorus removal (EBPR) microbial community and metabolic performance of five full-scale EBPR systems by using fluorescence in situ hybridisation combined with off-line batch tests fed with acetate under anaerobic-aerobic conditions. The phosphorus accumulating organisms (PAOs) in all systems were stable and showed little variability between each plant, while glycogen accumulating organisms (GAOs) were present in two of the plants. The metabolic activity of each sludge showed the frequent involvement of the anaerobic tricarboxylic acid cycle (TCA) in PAO metabolism for the anaerobic generation of reducing equivalents, in addition to the more frequently reported glycolysis pathway. Metabolic variability in the use of the two pathways was also observed, between different systems and in the same system over time. The metabolic dynamics was linked to the availability of glycogen, where a higher utilisation of the glycolysis pathway was observed in the two systems employing side-stream hydrolysis, and the TCA cycle was more active in the A(2)O systems. Full-scale plants that showed higher glycolysis activity also exhibited superior P removal performance, suggesting that promotion of the glycolysis pathway over the TCA cycle could be beneficial towards the optimisation of EBPR systems. PMID- 24210548 TI - Trends in hospital admissions for burns in England, 1991-2010: a descriptive population-based study. AB - OBJECTIVES: To describe trends in admissions to English hospitals and 30-day in hospital mortality associated with a primary diagnosis of burns. DESIGN: Descriptive population-based study. SETTING: England. PARTICIPANTS: Patients admitted to hospital with a primary diagnosis of burns between 1991 and 2010. MAIN OUTCOME MEASURES: Age-specific and age-standardised admission rates, and 30 day in-hospital mortality percentages. RESULTS: During 1991-2010, there were 188,597 admissions to hospitals in England with a primary diagnosis of burns. Annual numbers of admissions decreased between 1991 and 2002, followed by a steeper increase up to 2010. Rates were higher in males, in the age groups 0-4 and >=85 years, and in persons from deprived areas of residence, most ethnic minorities, and urban areas. There were 3196 in-hospital deaths within 30 days of admission for burns between 1991 and 2010. Between 2000 and 2010, this mortality decreased from 1.99% to 0.91%. The highest rates of 30-day in-hospital deaths occurred in the elderly and the lowest in children. CONCLUSION: Although in hospital mortality from burns has decreased in recent years, if the recent upward trend in hospital admissions is genuine, it will have resource implications for regional burns units, and also suggests the need for a renewed emphasis on primary prevention. Observed inequalities with respect to age, gender, deprivation, ethnicity, and urban-rural status provide a rational basis for targeting primary prevention initiatives. PMID- 24210549 TI - Prevalence, predictors, and outcomes in treatment-resistant hypertension in patients with coronary disease. AB - BACKGROUND: Increasingly, apparent treatment-resistant hypertension has been recognized. However, much of the prevalence, predictors, and outcomes are largely unknown, especially in patients with coronary artery disease. METHODS: We evaluated 10,001 patients with coronary artery disease who were enrolled in the Treating to New Targets trial. Apparent treatment-resistant hypertension was defined as blood pressure >= 140 mm Hg despite 3 antihypertensive agents or <140 mm Hg with >= 4 antihypertensive agents. The primary outcome was major cardiovascular events (composite of fatal coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke). RESULTS: Among the 10,001 patients in the trial, 1112 (11.1%) had apparent treatment-resistant hypertension. In a multivariable model adjusting for baseline differences, the treatment-resistant hypertension group had a 64% increase in primary outcome (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.39-1.94; P < .001), driven by a 69% increase in coronary heart disease death (HR, 1.69; 95% CI, 1.22, 2.34; P = .001) and 73% increase in nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.39-2.16, P < .0001) when compared with the no apparent treatment-resistant hypertension group. In addition, patients with apparent treatment-resistant hypertension had a 71% increase in major coronary event (P < .0001), 45% increase in death (P = .001), 33% increase in heart failure (P = .05), 53% increase in any cardiovascular event (P < .0001), 60% increase in any coronary event (P < .0001), 68% increase in angina (P < .0001), and 51% increase in coronary revascularization (P < .0001) when compared with the no apparent treatment resistant hypertension group. Results were largely similar whether the definition of apparent treatment-resistant hypertension was based on a blood pressure >= 140 mm Hg despite 3 agents or a blood pressure <140 mm Hg with >= 4 agents. CONCLUSIONS: In patients with coronary artery disease, apparent treatment resistant hypertension is associated with a marked increase in the risk of cardiovascular morbidity and mortality, including an increase in all-cause death. PMID- 24210550 TI - Potential of aeration flow rate and bio-char addition to reduce greenhouse gas and ammonia emissions during manure composting. AB - Aeration is an important factor influencing CO2, CH4, N2O and NH3 emissions from the composting process. Both CH4 and N2O are potent greenhouse gases (GHG) of high importance. Here, we examined the effects of high and low aeration rates together with addition of barley straw with and without bio-char on GHG and NH3 emissions from composting cattle slurry and hen manure in small-scale laboratory composters. Depending on treatment, cumulative C losses via CO2 and CH4 emissions accounted for 11.4-22.5% and 0.004-0.2% of initial total carbon, while N losses as N2O and NH3 emissions comprised 0.05-0.1% and 0.8-26.5% of initial total nitrogen, respectively. Decreasing the flow rate reduced cumulative NH3 losses non-significantly (by 88%) but significantly increased CH4 losses (by 51%) from composting of cattle slurry with barley straw. Among the hen manure treatments evaluated, bio-char addition to composting hen manure and barley straw at low flow rates proved most effective in reducing cumulative NH3 and CH4 losses. Addition of bio-char in combination with barley straw to hen manure at both high and low flow rates reduced total GHG emissions (as CO2-equivalents) by 27-32% compared with barley straw addition alone. Comparisons of flow rates showed that low flow could be an alternative strategy for reducing NH3 losses without any significant change in N2O emissions, pointing to the need for well-controlled composting conditions if gaseous emissions are to be minimised. PMID- 24210551 TI - Heterogeneous reactions of particulate benzo[b]fluoranthene and benzo[k]fluoranthene with NO(3) radicals. AB - Benzo[b]fluoranthene (B[b]F) and benzo[k]fluoranthene (B[k]F) are widespread priority pollutants of polycyclic aromatic hydrocarbons (PAHs), which can react with atmospheric oxidants during transport in the troposphere and lead to the formation of more toxic compounds. At present, the rates of heterogeneous reactions of B[b]F and B[k]F aerosols with NO3 radicals, an important atmospheric oxidant, are not fully understood. Thus, this study investigated the products and kinetics of heterogeneous reactions of suspended B[b]F and B[k]F particles with NO3 radicals in an aerosol reaction chamber at room temperature (293+/-2K) under atmospheric pressure. The reactions are monitored online using a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer (VUV-ATOFMS) and an atmospheric gas analysis mass spectrometer. The mono-nitro-, di-nitro-, tri-nitro-products, and those products containing both nitro and ketone groups are observed with VUV-ATOFMS. The effective rate constants for heterogeneous reactions of particulate B[b]F and B[k]F with NO3 radicals under the experimental conditions are respectively estimated to (1.2+/-0.1)*10(-12)cm(3)molecule(-1)s( 1) and (5.8+/-0.3)*10(-13)cm(3)molecule(-1)s(-1) using a mixed-phase relative rate method, and the corresponding effective uptake coefficients are respectively estimated to 0.22 and 0.65. The lifetimes of particulate B[b]F and B[k]F at a typical concentration of NO3 radicals (5*10(8)moleculecm(-3)) in the lower troposphere during the night are estimated to 3.0 and 3.9h, respectively. The experimental results of these heterogeneous reactions in the aerosol state provide supplementary knowledge for kinetic behaviors of airborne PAHs particles. PMID- 24210552 TI - Bioconcentration, metabolism, and biomarker responses in freshwater fish Carassius auratus exposed to roxithromycin. AB - To investigate the distribution, bioconcentration, metabolism, and biomarker responses of macrolide antibiotic roxithromycin (ROX) in fish, crucian carp (Carassius auratus) were exposed to various concentrations of ROX (4, 20, and 100MUgL(-1)) for 20d. The ROX content in different tissues was quantified using UPLC/MS/MS. The liver exhibited the highest ROX concentration followed by the bile, gills, and muscle tissues. After 15d of exposure to different concentrations of ROX, the bioconcentration factors were 2.15-38.0 in the liver, 0.950-20.7 in the bile, 0.0506-19.7 in the gill, and 0.0439-13.8 in the muscle; these results were comparable to the estimated BCF values. The metabolites formed in the bile were identified based on metabolic identification in human bile. Additionally, the biomarkers, including acetylcholinesterase in the brain, as well as 7-ethoxyresorufin O-deethylase and superoxide dismutase in the liver changed significantly after 5, 10, 15, and 20d of exposure (P<0.05). Our results suggest that ROX can accumulate and be metabolized in fish; therefore, interactions between ROX or its metabolites and the biological systems may induce biochemical disturbances in fish. PMID- 24210553 TI - Development and mapping of seleniferous soils in northwestern India. AB - Periodic surveys were undertaken to identify and characterize Se-contaminated soils in northwestern India. Total Se content varied from 0.023 to 4.91mgkg(-1) in 0-15cm surface soil and 0.64-515.0mgkg(-1) in samples of vegetation. Selenium contaminated land occupying an area of 865ha was classified into different categories based on total Se content of soils as moderately contaminated (0.5 2.0mg Sekg(-1)) and highly contaminated (>2.0mg Sekg(-1)). The normal soils contained <0.5mg Sekg(-1). The soil map was prepared using village level cadastral maps. Se-contaminated soils were silty loam to silty clay loam in texture and tested pH 7.9-8.8, electrical conductivity 0.3-0.7dSm(-1), calcium carbonate 0.1-4.1% and organic carbon 0.4-1.0%. Selenium was present throughout the soil profile up to 2m depth; 0-15cm surface soil layer contained 1.5 to 6.0 times more Se than in subsurface layers. Selenium content in rock samples collected from lower and upper Shiwalik sub-Himalayan ranges varied from 1864 to 2754 and 11 to 847MUgkg(-1), respectively. The sediments transported through seasonal rivulets linking the Shiwalik ranges to affected sites contained 0.57 2.89mg Sekg(-1). The underground water containing 2.5-69.5MUg SeL(-1) used for irrigating transplanted rice grown in Se-contaminated area resulted in a net Se addition in soil up to 881gha(-1)y(-1); possibly further aggravating the Se toxicity problem. Presence of substantial amount of Se in rock samples and sediments of seasonal rivulets suggests that Se-rich materials are being transported from Shiwalik hills and deposited in regions where seasonal rivulets end up. PMID- 24210554 TI - Anaerobic reductive dechlorination of 1,2,3,4-tetrachlorodibenzofuran in polychlorinated dibenzo-p-dioxin- and dibenzofuran-contaminated sediments of the Kymijoki River, Finland. AB - Sediments of the Kymijoki River are highly contaminated with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). These persistent PCDD/Fs resist biotic degradation and therefore the potential for microbial reductive dechlorination was assessed to determine how microbes impact the fate of these compounds. Anaerobic sediment microcosms of five different sites in the river were spiked with 1,2,3,4-tetrachlorodibenzofuran (1,2,3,4-TeCDF) as a model compound to determine the dechlorination potential in the sediments. Dechlorinating bacteria were active in all the study sites of the river. The extent of dechlorination over 10 and 29 months corresponded to the levels of aged PCDD/Fs, with sediments of the most contaminated site at Kuusankoski being the most active for reductive dechlorination. The dechlorination activity and levels of aged PCDD/Fs were correlated within the sediment cores at the all sites. The pathway of 1,2,3,4-TeCDF dechlorination was mainly via 1,3,4 trichlorodibenzofuran (TrCDF) to 1,3-dichlorodibenzofuran (DiCDF). Dechlorination via 1,2,4-TrCDF to further dechlorination products was also detected. Lateral reductive dechlorination would decrease the toxicity of 2,3,7,8-substituted PCDD/Fs. Our data suggest that sediments of the Kymijoki River contain indigenous microorganisms that are responsible for dechlorination of PCDD/Fs, especially at the most contaminated site. PMID- 24210555 TI - Production of an aminoterminally truncated, stable type of bioactive mouse fibroblast growth factor 4 in Escherichia coli. AB - In mice, fibroblast growth factor 4 (Fgf4) is a crucial gene for the generation of trophectoderm, progenitor cells of the placenta. Therefore, exogenous FGF4 promotes the isolation and maintenance of trophoblast stem cells from preimplantation embryos. We previously produced a 6* histidine (His)-tagged, mouse FGF4 (Pro(31)-Leu(202)) without a secretory signal peptide at the amino terminus, referred to as HismFGF4, in Escherichia coli. Here, we found that HismFGF4 was unstable, such as in phosphate-buffered saline. In these conditions, site-specific cleavage between Ser(50) and Leu(51) was identified. In order to generate stable mouse FGF4 derivatives, a 6* His-tagged mouse FGF4 (Leu(51) Leu(202)), termed HismFGF4L, was expressed in E. coli. HismFGF4L could be purified from the supernatant of cell lysates by heparin column chromatography. In phosphate-buffered saline, HismFGF4L was relatively stable. HismFGF4L exerted significant mitogenic activities at concentrations as low as 0.01 nM (P < 0.01) in mouse embryonic fibroblast Balb/c 3T3 cells expressing FGF receptor 2. In the presence of PD173074, an FGF receptor inhibitor, the growth-promoting activity of HismFGF4L was abolished. Taken together, we suggest that aminoterminally truncated HismFGF4L is capable of promoting the proliferation of mouse-derived cells via an authentic FGF signaling pathway. We consider that HismFGF4L is useful as a derivative of mouse FGF4 protein for analyzing the effects of mouse FGF4 and for stimulating cell growth of mouse-derived cells, such as trophoblast stem cells. Our study provides a simple method for the production of a bioactive, stable mouse FGF4 derivative in E. coli. PMID- 24210556 TI - One of these things is not like the other: distinctiveness and executive function in preschoolers. AB - There is scant evidence that children younger than 7 years show a memory advantage for distinct information, a memory phenomenon termed the isolation effect (Journal of Experimental Psychology: Learning, Memory, and Cognition, 2001, Vol. 27, pp. 1359-1366). We investigated whether 4-, 5-, and 6-year-olds' developing organizational processing and executive function contributed to the isolation effect, demonstrated when recall was better for a semantically unique target (e.g., sheep, pig, watermelon, duck) rather than a semantically common target (e.g., apple, banana, watermelon, strawberry). To encourage organizational processing, children were asked to categorize each item presented. Children also completed working memory and cognitive flexibility tasks, and only children who scored high in cognitive flexibility demonstrated the isolation effect. PMID- 24210557 TI - Determination of non-ionic and anionic surfactants in industrial products by separation on a weak ion-exchanger, derivatization and liquid chromatography. AB - A method for the determination of priority surfactants, including fatty alcohol ethoxylates (FAE), alkylether sulfates (AES) and linear alkylbenzene sulfonates (LAS) is described. The samples were diluted with 50% methanol at pH 4 prior to solid-phase extraction on a weak anionic exchanger (WAX). The AES and LAS surfactant classes were retained, whereas the non-ionic components, including most FAE oligomers were eluted. After washing the WAX cartridge to remove cations, the remaining hydrophobic FAE oligomers were eluted using hot 80% methanol at pH 4 (at ca. 50 degrees C). These two eluates were combined to constitute the non-ionic fraction. Then, AES and LAS were eluted using 80% MeOH with 3M NH3 followed by 95% methanol with 0.75M NH3. The two eluates obtained in basic media were combined to constitute the anionic fraction. The solvents were evaporated, the residues were dissolved in 1,4-dioxane, and esterification of the alcohols and transesterification of AES with phthalic anhydride was performed. Separation of the derivatized oligomers was achieved by gradient elution on a C8 column with acetonitrile/water in the presence of 0.1% acetic acid and 0.1M NaClO4. The chromatogram of the non-ionic fraction showed the peaks of the resolved FAE oligomers. The chromatogram of the anionic fraction showed the peaks of the LAS homologues well resolved from those of the AES oligomers. The method was applied to laundry and industrial cleaners, shampoos and a shower gel. PMID- 24210558 TI - Accurate on-line mass flow measurements in supercritical fluid chromatography. AB - This work demonstrates the possible advantages and the challenges of accurate on line measurements of the CO2 mass flow rate during supercritical fluid chromatography (SFC) operations. Only the mass flow rate is constant along the column in SFC. The volume flow rate is not. The critical importance of accurate measurements of mass flow rates for the achievement of reproducible data and the serious difficulties encountered in supercritical fluid chromatography for its assessment were discussed earlier based on the physical properties of carbon dioxide. In this report, we experimentally demonstrate the problems encountered when performing mass flow rate measurements and the gain that can possibly be achieved by acquiring reproducible data using a Coriolis flow meter. The results obtained show how the use of a highly accurate mass flow meter permits, besides the determination of accurate values of the mass flow rate, a systematic, constant diagnosis of the correct operation of the instrument and the monitoring of the condition of the carbon dioxide pump. PMID- 24210559 TI - Ventral inlay labia minora graft urethroplasty for the management of female urethral strictures. AB - OBJECTIVE: To evaluate the functional outcomes of ventral inlay labia minora graft urethroplasty (VILGU) for the management of female urethral strictures. METHODS: Data of 7 consecutive women treated with VILGU between 2011 and 2013 were reviewed. Two patients had cystostomy tubes at repair, and 5 had undergone previous urethral dilations and urethrotomies. Clinical evaluation included assessment of the effect of voiding symptoms with American Urological Association (AUA) symptom score, uroflowmetry, voiding cystourethrography, and intraoperative urethrocystoscopy using a 6.5F pediatric ureterorenoscope. Preoperative AUA symptom score and peak urinary flow rate were compared with postoperative values. Cure was defined as the absence of any restenosis requiring additional intervention with subjective patient satisfaction at the last follow-up. RESULTS: Mean stricture length was 1.5 cm (range, 1-2.5), and mean operative time was 95 minutes (range, 70-110). With a mean follow-up of 18.2 months (range, 3-30), cure was achieved in 6 (86%) women. At the last follow-up, mean maximum urine flow (mL/s) increased from 3.9 +/- 3.1 preoperatively to 22.7 +/- 8.3 postoperatively (P <.001), and mean AUA symptom score decreased from 25.3 +/- 5.2 preoperatively to 6.9 +/- 3.7 postoperatively (P = .001). No fistulae developed after surgery. "De-novo" stress urinary incontinence was not evident in any case. CONCLUSION: VILGU effectively provides better urinary flow and significantly improves patient satisfaction in patients with female urethral stricture disease. PMID- 24210560 TI - Vasectomy reversal outcomes among patients with vasal obstructive intervals greater than 10 years. AB - OBJECTIVE: To analyze the vasectomy reversal (VR) outcomes specifically among patients with vasal obstructive intervals (VOIs) of >10 years. The VOI has been shown to be a significant predictor of outcome after VR. Although no strict cutoff exists, couples have frequently been discouraged from considering a VR strictly according to the interval from vasectomy. MATERIALS AND METHODS: From 2006 to 2011, all consecutive VRs performed by 2 fellowship-trained microsurgeons were analyzed. The patients were stratified into 4 categories according to the duration of the VOI: <10, 10-15, >15-20, and >20 years. The postoperative semen parameters, patency rates, and pregnancy outcomes were compared among the 4 groups. RESULTS: Of 535 consecutive VRs, 177 patients (33%) had a VOI of >10 years. The couple characteristics, type of VR required, postoperative semen quality, and patency and pregnancy rates among the 4 groups were analyzed. The men with longer VOIs were older (P <.001) and had older female partners (P = .006). Although the VOI influenced the type of reversal performed, favorable semen concentrations (average >20 million/mL in all groups) and patency (average >90%) and pregnancy rates (range 24%-39%) were achieved in men with a VOI >10 years. CONCLUSION: Although the interval since vasectomy has a significant effect on the type of VR required, provided a surgeon is proficient in both microsurgical vasovasostomy and vasoepididymostomy, favorable semen parameters and patency and pregnancy rates can be achieved in men with a VOI >10 years. Couples should not be discouraged from considering VR simply according to the VOI. PMID- 24210561 TI - Editorial comment. PMID- 24210564 TI - Editorial comment. PMID- 24210565 TI - Comparison of sperm retrieval and intracytoplasmic sperm injection outcome in patients with and without Klinefelter syndrome. AB - OBJECTIVE: To evaluate microsurgical testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) treatment in patients with non-mosaic Klinefelter syndrome (KS). METHODS: We retrospectively evaluated the micro TESE/ICSI performance in 134 patients with classic KS and 537 men with nonobstructive azoospermia (NOA) and normal karyotype referred to Royan Institute between 2009 and 2011. The patients were divided into 2 groups according to micro TESE outcome. Several factors, including patients' age, level of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, were compared between the 2 groups. RESULTS: Sperm retrieval rate by micro-TESE in the KS and control groups were 28.4% (38/134) and 22.2% (119/537), respectively. In the KS group, the mean age of patients with successful sperm retrieval of spermatozoa was significantly lower than those with negative results (30.0 +/- 0.65 vs 33.68 +/- 0.6 year, P = .001) and comparison of laboratory parameters between the 2 groups showed that the level of testosterone was significantly higher in patients with successful sperm retrieval (3.4 +/- 0.48 vs 2.33 +/- 0.23 ng/mL, P <.001). The fertilization rate was significantly higher in the KS group than the control group (28% vs 21%, P = .038). Also, live birth rate per embryo transfer was higher in the KS group, but it was not significant (13% vs 3%, P = .05). CONCLUSION: This study of sperm recovery and ICSI outcome in men with and without KS shows that micro-TESE/ICSI is a successful intervention for the majority of men with KS. PMID- 24210566 TI - Bladder function evaluation before renal transplantation in nonurologic disease: is it necessary? AB - OBJECTIVE: To determine whether preoperative cystometry and a pressure flow study (PFS) are necessary in patients with end-stage renal disease from nonurologic causes who will undergo renal transplantation. METHODS: From April 2009 to June 2010, 30 patients scheduled to undergo renal transplantation were prospectively evaluated with cystometry and PFS. The evaluation was performed immediately before and 6 months after renal transplantation. The inclusion criteria were age >18 years and end-stage renal disease secondary to nonurologic disease. RESULTS: Improvement in the cystometry and PFS parameters was observed after the return of diuresis at 6 months after transplantation. The parameter changes from baseline to the 6-month evaluation were as follows: first sensation of bladder filling, 88.8-168.7 mL (P = .0005); first desire to void, 137.2-251.1 mL (P <.0001); maximal cystometric capacity, 221.2-428.7 mL (P <.0001); bladder compliance, 73.9 138.6 mL/cm H2O (P = .03); and maximal flow rate, 8.1-15.8 mL/s (P <.0001). The Abrams-Griffiths number in the men decreased from 31.8 to 15.2 (P = .002). No significant changes were observed in the detrusor pressure at the maximal flow rate or the postvoid residual urine volume. Patients with a 24-hour urine output <200 mL tended to have had significantly worse parameters before transplantation. CONCLUSION: Significant improvement in the cystometry and PFS parameters was observed in patients with end-stage renal disease, without urologic disease, 6 months after transplantation, and was associated with recovery of the glomerular filtration rate and urine output by the renal graft. PMID- 24210567 TI - Editorial comment. PMID- 24210568 TI - External validation of a preoperative renal stone grading system: reproducibility and inter-rater concordance of the Guy's stone score using preoperative computed tomography and rigorous postoperative stone-free criteria. AB - OBJECTIVE: To validate the Guy's stone score (GSS) using preoperative computed tomography (CT) and to assess its inter-rater concordance and association with rigorous definitions of stone clearance. METHODS: The preoperative CT scans of 166 consecutive percutaneous nephrolithotomy (PCNL) patients treated by a single surgeon were independently reviewed by 2 urology residents and graded according to GSS. Concordance was calculated using Cohen's kappa score. Residual fragments (RFs) were evaluated on CT or plain radiography on postoperative day 1. GSS was correlated with 3 different outcomes; RFs <4 mm, RFs <2 mm, or no RFs. RESULTS: Higher GSS was associated with decreased stone clearance by any metric on a CT scan: RFs <4 mm (P = .03), RFs <2 mm (P = .02), or no RFs (P = .02). On plain radiography, higher GSS was only associated with lower likelihood of no RFs (P <.005). Inter-rater concordance was good (kappa = 0.72), with 78% of cases categorized the same by both raters. Twelve of 36 cases (33%) of disagreement were between categories II and III and 20 of 36 cases (56%) pertained to unclear definitions of "partial staghorn stone" and "abnormal anatomy." CONCLUSION: The GSS is a straightforward grading system of the complexity of renal stones. When applied to preoperative CT scans, it offers good inter-rater concordance and is associated with rigorous endpoints of stone clearance. The inter-rater concordance could be further improved by explicit definitions of abnormal anatomy, partial vs complete staghorn stones, and the size of a calculus that constitutes a separate stone. PMID- 24210569 TI - Spinal anesthesia is an efficient and safe anesthetic method for percutaneous nephrolithotomy. AB - OBJECTIVE: To investigate the effect of spinal anesthesia (SA) vs general anesthesia (GA) administration on the safety and efficiency of percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively evaluated 1478 patients who underwent PCNL in our clinic between 2004 and 2011. We excluded the patients with bilateral PCNL, renal abnormality, or solitary kidney. The remaining 1004 adult patients were divided into 2 groups according to anesthesia administration as GA (n = 564) or SA (n = 440). The groups were compared according to operative and postoperative properties. Complications of PCNL were evaluated according to the modified Clavien classification. Independent t test, chi-square test, and analysis of covariance were used for the comparison of groups. RESULTS: The durations of hospitalization, operation, and fluoroscopy of patients in the SA group were significantly shorter than that of the patients in the GA group (P <.01). The number of patients with postoperative requirement of narcotic analgesic and blood transfusion was significantly higher in the GA group (P <.01). The GA group had more grades 2, 3a, 3b, and 4b complications according to modified Clavien classification (P <.05). The significant differences in postoperative analgesic requirement and hospitalization duration between the groups did not affect postoperative urinary drainage (P <.01; adjusted r(2) = 0.064). CONCLUSION: PCNL with SA demonstrated shorter hospitalization, operation, and fluoroscopy durations. GA has some disadvantages as a greater requirement of narcotic analgesic and greater frequency of major complications. SA administration is a safe and effective method in appropriately selected patients with PCNL. PMID- 24210570 TI - Role of alpha-blockers in the treatment of stent-related symptoms: a prospective randomized control study. AB - OBJECTIVE: To properly use the Ureteric Symptom Score Questionnaire (USSQ) to evaluate, in a randomized control study, the effect of 2 different alpha-blockers in improving symptoms and quality of life in patients with indwelling ureteral stents. METHODS: After institutional review board approval, 150 consecutive patients with a double-J ureteral stent inserted after extracorporeal shockwave lithotripsy (ESWL) or ureteroscopic stone treatment were randomly assigned to receive tamsulosin 0.4 mg, alfuzosin 10 mg, or placebo. The validated USSQ was completed 1 and 4 weeks after stent insertion and 4 weeks after stent removal. The Kruskal-Wallis test for independent samples for non-normally distributed ordinal variables, chi-square to compare proportions or differences, and 1-way analysis of variance (ANOVA) for independent samples to compare for differences in case of continuous variables were used for statistical analysis of the results. RESULTS: Patients receiving alpha-blockers expressed an overall statistically significant lower urinary (P <.001), pain (P <.001 with stent in situ), and general health index (P <.002) scores. Sexual life and quality of life were also positively influenced. Quality of work was not influenced. No patients had to discontinue medication because of side effects or underwent stent removal before the due date. There was no difference in various outcomes between the 2 alpha-blockers. CONCLUSION: Stent-related morbidity is a reality in the majority of patients. Simple medication, such as alpha-blockers, reduce stent-related symptoms and the negative impact on quality of life. It seems that stent-related symptom improvement is independent to the type of alpha-blocker. PMID- 24210571 TI - Comparison of pediatric robotic-assisted laparoscopic nephroureterectomy and laparoendoscopic single-site nephroureterectomy. AB - OBJECTIVE: To compare outcomes between pediatric robotic-assisted laparoscopic nephroureterectomy (RALNU) and laparoendoscopic single-site nephroureterectomy (LESSNU). METHODS: A retrospective cohort study was performed of all patients who underwent RALNU and LESSNU at a single pediatric institution from April 2009 to April 2013. Patient demographics, perioperative details, and outcomes were reviewed. RESULTS: Thirty-two patients (20 men, 12 women) were identified. Twenty four patients underwent RALNU and 8 patients underwent LESSNU. There was no significant blood loss, intraoperative complication, or conversion to open or standard laparoscopy for either procedure. Median age was 55.1 months (range 4.5 171.8 months) for RALNU and 51.6 months (range 16.3-144.9 months) for LESSNU (P = .695). Median weight was 19.1 kg (range 7-55 kg) for RALNU and 16.9 kg (range 11 41 kg) for LESSNU (P = .727). Median operative time was 227 minutes (range 112 362 minutes) for RALNU and 174 minutes (range 74-288 minutes) for LESSNU (P = .028). Median length of hospital stay was 2 days (range 1-4 days) for RALNU and 1 day (range 0-6 days) for LESSNU (P = .134). Median in-patient postoperative narcotic use of morphine-equivalent was 0.03 mg/kg/day (range 0-0.2) for RALNU and <0.01 mg/kg/day (range 0-0.2) for LESSNU (P = .134). Median in-patient postoperative Ketorolac use was <0.01 mg/kg/day (range 0-0.8) for RALNU and <0.01 mg/kg/day (range 0-0.5) for LESSNU (P = .784). Median follow-up was 22 months (range 0.8-48.4 months) for RALNU and 18.8 months (range 0.3-29.4 months) for LESSNU (P = .361). We observed 2 complications (8.3%) in RALNU and 1 in LESSNU (P = 1). CONCLUSION: LESSNU has a significantly shorter operative time with comparable in-patient postoperative narcotics use as compared to RALNU. PMID- 24210572 TI - Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy. AB - BACKGROUND: Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. PATIENTS AND METHODS: Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. RESULTS: Seventy seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings. CONCLUSION: Our analysis shows that response rates and PFS to first line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias. PMID- 24210573 TI - [Dyspepsia with alarm symptoms: endoscopy yes, but ultrasound as well]. PMID- 24210575 TI - Tembusu virus infection in Cherry Valley ducks: the effect of age at infection. AB - Three groups of Cherry Valley ducks at 5 day, 2 week and 5 week of age were intranasally infected with the WFCL strain of Tembusu virus (TMUV) to investigate the effect of host age on the outcome of TMUV infection. For each age group, clinical signs, gross and microscopic lesions, viral copy numbers in tissues and serum neutralizing antibody titers were recorded. Age-related differences in the resistance to TMUV infection were observed with younger ducks being more susceptible. Some ducks infected at 5 day and 2 week of age developed severe clinical signs, including severe neurological dysfunction and death. However, subclinical signs and no mortality were observed in ducks infected at 5 week of age. A decline in the severity of gross and microscopic lesions was observed as ducks mature. Systemic infections were established in the three age groups post challenge. Higher viral copy numbers in the tissues, especially in vital organs such as the brain and the heart, were developed in the ducks infected at 5 day of age than older ducks, correlating with the severity of clinical signs and lesions in the tissues. Furthermore, ducks infected at 5 week of age developed significantly higher serum neutralizing antibody titers than ducks infected at 5 day of age as determined by serum neutralization test. Therefore, age-related differences in the resistance to TMUV infection should be considered when studying the pathogenicity, pathogenesis, formulation of the vaccination and therapy strategies of TMUV infection in ducks. PMID- 24210576 TI - Equine infectious diseases. PMID- 24210574 TI - Movement variability near goal equivalent manifolds: fluctuations, control, and model-based analysis. AB - Fluctuations in the repeated performance of human movements have been the subject of intense scrutiny because they are generally believed to contain important information about the function and health of the neuromotor system. A variety of approaches has been brought to bear to study these fluctuations. However it is frequently difficult to understand how to synthesize different perspectives to give a coherent picture. Here, we describe a conceptual framework for the experimental study of motor variability that helps to unify geometrical methods, which focus on the role of motor redundancy, with dynamical methods that characterize the error-correcting processes regulating the performance of skilled tasks. We describe how goal functions, which mathematically specify the task strategy being employed, together with ideas from the control of redundant systems, allow one to formulate simple, experimentally testable dynamical models of inter-trial fluctuations. After reviewing the basic theory, we present a list of five general hypotheses on the structure of fluctuations that can be expected in repeated trials of goal-directed tasks. We review recent experimental applications of this general approach, and show how it can be used to precisely characterize the error-correcting control used by human subjects. PMID- 24210577 TI - [Severe shock after protamine infusion in a neonate undergoing cardio pulmonary bypass]. AB - Shock after protamine infusion are rare. We report here the case of a 6-day-old boy having presented severe and recurring hypotensions after protamine infusions during cardiac surgery under cardio pulmonary bypass. The physiopathology of these reactions is complex and, in the presented case, involved mechanism may not be anaphylactic. PMID- 24210578 TI - How do coverage policies influence practice patterns, safety, and cost of initial lumbar fusion surgery? A population-based comparison of workers' compensation systems. AB - BACKGROUND CONTEXT: In response to increasing use of lumbar fusion for improving back pain, despite unclear efficacy, particularly among injured workers, some insurers have developed limited coverage policies. Washington State's workers' compensation (WC) program requires imaging confirmation of instability and limits initial fusions to a single level. In contrast, California requires coverage if a second opinion supports surgery, allows initial multilevel fusion, and provides additional reimbursement for surgical implants. There are no studies that compare population-level effects of these policy differences on utilization, costs, and safety of lumbar fusion. PURPOSE: The purpose of this study was to compare population-level data on the use of complex fusion techniques, adverse outcomes within 3 months, and costs for two states with contrasting coverage policies. STUDY DESIGN AND SETTING: The study design was an analysis of WC patients in California and Washington using the Agency for Healthcare Research and Quality's State Inpatient Databases, 2008-2009. PATIENT SAMPLE: All patients undergoing an inpatient lumbar fusion for degenerative disease (n=4,628) were included the patient sample. OUTCOME MEASURE(S): Outcome measures included repeat lumbar spine surgery, all-cause readmission, life-threatening complications, wound problems, device complications, and costs. METHODS: Log-binomial regressions compared 3 month complications and costs between states, adjusting for patient characteristics. RESULTS: Overall rate of lumbar fusion operations through WC programs was 47% higher in California than in Washington. California WC patients were more likely than those in Washington to undergo fusion for controversial indications, such as nonspecific back pain (28% versus 21%) and disc herniation (37% versus 21%), as opposed to spinal stenosis (6% versus 15%), and spondylolisthesis (25% versus 41%). A higher percentage of patients in California received circumferential procedures (26% versus 5%), fusion of three or more levels (10% versus 5%), and bone morphogenetic protein (50% versus 31%). California had higher adjusted risk for reoperation (relative risk [RR] 2.28; 95% confidence interval [CI], 2.27-2.29), wound problems (RR 2.64; 95% CI, 2.62 2.65), device complications (RR 2.49; 95% CI, 2.38-2.61), and life-threatening complications (RR 1.31; 95% CI, 1.31-1.31). Hospital costs for the index procedure were greater in California ($49,430) than in Washington ($40,114). CONCLUSIONS: Broader lumbar fusion coverage policy was associated with greater use of lumbar fusion, use of more invasive operations, more reoperations, higher rates of complications, and greater inpatient costs. PMID- 24210579 TI - Continuous cervical spine kinematics during in vivo dynamic flexion-extension. AB - BACKGROUND CONTEXT: A precise and comprehensive definition of "normal" in vivo cervical kinematics does not exist due to high intersubject variability and the absence of midrange kinematic data. In vitro test protocols and finite element models that are validated using only end range of motion data may not accurately reproduce continuous in vivo motion. PURPOSE: The primary objective of this study was to precisely quantify cervical spine intervertebral kinematics during continuous, functional flexion-extension in asymptomatic subjects. The advantages of assessing continuous intervertebral kinematics were demonstrated by comparing asymptomatic controls with patients with single-level anterior arthrodesis. STUDY DESIGN: Cervical spine kinematics were determined during continuous in vivo flexion-extension in a clinically relevant age group of asymptomatic controls and a group of patients with C5-C6 arthrodesis. PATIENT SAMPLE: The patient sample consisted of 6 patients with single-level (C5-C6) anterior arthrodesis (average age: 48.8+/-6.9 years; 1 male, 5 female; 7.6+/-1.2 months postsurgery) and 18 asymptomatic control subjects of similar age (average age: 45.6+/-5.8 years; 5 male, 13 female). OUTCOME MEASURES: Outcome measures included the physiologic measure of continuous kinematic motion paths at each cervical motion segment (C2 C7) during flexion-extension. METHODS: Participants performed flexion-extension while biplane radiographs were collected at 30 images per second. A previously validated tracking process determined three-dimensional vertebral positions with submillimeter accuracy. Continuous flexion-extension rotation and anterior posterior translation motion paths were adjusted for disc height and static orientation of each corresponding motion segment. RESULTS: Intersubject variability in flexion-extension angle was decreased 15% to 46% and intersubject variability in anterior-posterior translation was reduced 14% to 33% after adjusting for disc height and static orientation angle. Average intersubject variability in continuous motion paths was 1.9 degrees in flexion-extension and 0.6 mm in translation. Third-order polynomial equations were determined to precisely describe the continuous flexion-extension and anterior-posterior translation motion path at each motion segment (all R2>0.99). CONCLUSIONS: A significant portion of the intersubject variability in cervical kinematics can be explained by the disc height and the static orientation of each motion segment. Clinically relevant information may be gained by assessing intervertebral kinematics during continuous functional movement rather than at static, end range of motion positions. The fidelity of in vitro cervical spine mechanical testing protocols may be evaluated by comparing in vitro kinematics to the continuous motion paths presented. PMID- 24210580 TI - Defining age-related differences in outcome after traumatic spinal cord injury: analysis of a combined, multicenter dataset. AB - BACKGROUND CONTEXT: The existing evidence suggests that, although older spinal cord injury (SCI) patients experience a similar degree of neurologic recovery to younger patients, older patients experience diminished functional outcomes at follow-up. However, all studies have assumed that the impact of age on functional outcome is the same across the spectrum of injury severity. PURPOSE: To test this assumption, we evaluated age as a potential effect moderator governing the relationship between acute neurologic status and long-term functional outcome. STUDY DESIGN/SETTING: Combined analysis of two prospective SCI datasets enrolling patients from North American trauma centers over the last decade. PATIENT SAMPLE: Adult patients (>=16 years old) with traumatic SCI and a standardized American Spinal Injury Association (ASIA) neurologic examination performed within 3 days of injury. OUTCOME MEASURES: Functional independence measure (FIM) motor score at the 1-year follow-up was the primary outcome of interest. METHODS: To define older and younger age groups, age was dichotomized at a threshold of 65 years old. A sensitivity analysis was also performed by dichotomizing age at 60 years. Multivariable linear regression was used to investigate the moderating effects of age on the relationship between acute ASIA Impairment Scale (AIS) grade and follow-up FIM motor score. An interaction plot was generated to understand how the effect of age on functional outcome changed depending on the acute AIS grade. A second linear regression model investigating the moderating effects of age was produced that adjusted for additional relevant predictor variables. RESULTS: Of 729 patients, 376 met the eligibility criteria. The mean age was 43.2 (+/-16.9), with a total of 41 patients (10.9%) older than 65 years. In the univariable analysis there was no age-related difference in motor recovery or AIS grade conversion at follow-up; however, there was a significantly lower mean FIM motor score observed among the older group at 1 year (p=.03). In the multivariable analysis, age was found to have a significant moderating effect on the relationship between acute AIS grade and future functional status (p<.05). The interaction plot revealed that, although older patients had decreased follow-up FIM motor scores overall, this effect was greatest for AIS B and AIS C patients and lesser for AIS A and AIS D patients. After adjustment for additional covariates in the second linear model, these results remained unchanged. CONCLUSIONS: Overall, advanced age is associated with worse functional outcome after SCI; however, this effect varies across the spectrum of injury severity. These results will help to facilitate enhanced clinical communication as well as potentially aid in the development of customized treatment and rehabilitation protocols. PMID- 24210581 TI - Interreader and intermodality reliability of standard anteroposterior radiograph and magnetic resonance imaging in detection and classification of lumbosacral transitional vertebra. AB - BACKGROUND CONTEXT: Different types of lumbosacral transitional vertebra (LSTV) are classified based on the relationship of the transverse process of the last lumbar vertebra to the sacrum. The Ferguson view (30 degrees angled anteroposterior [AP] radiograph) is supposed to have a sufficient interreader reliability in classification of LSTV, but is not routinely available. Standard AP radiographs and magnetic resonance imaging (MRI) are often available, but their reliability in detection and classification of LSTV is unknown. PURPOSE: The purpose of this study was to evaluate the interreader reliability of detection and classification of LSTV with standard AP radiographs and report its accuracy by use of intermodality statistics compared with MRI as the gold standard. STUDY DESIGN/SETTING: Retrospective case control study. PATIENT SAMPLE: A total of 155 subjects (93 cases: LSTV type 2 or higher; 62 controls). OUTCOME MEASURES: Interreader reliability in detection and classification of LSTV using standard AP radiographs and coronal MRI as well as accuracy of radiographs compared with MRI. METHODS: After institutional review board approval, coronal MRI scans and conventional AP radiographs of 155 subjects (93 LSTV type 2 or higher and 62 controls) were retrospectively reviewed by two independent, blinded readers and classified according to the Castellvi classification. Interreader reliability was assessed using kappa statistics for detection of an LSTV and identification of all subtypes (six variants; 1: no LSTV or type I, 2: LSTV type 2a, 3: LSTV type 2b, 4: LSTV type 3a, 5: LSTV type 3b, 6: LSTV type 4) for MRI scans and standard AP radiographs. Further, accuracy and positive and negative predictive values were calculated for standard AP radiographs to detect and classify LSTV using MRI as the gold standard. RESULTS: The interreader reliability was at most moderate for the detection (k=0.53) and fair for classification (wk=0.39) of LSTV in standard AP radiograph. However, the interreader reliability was very good for detection (k=0.93) and classification (wk=0.83) of LSTV in MRI. The accuracy and positive and negative predictive values of standard AP radiograph were 76% to 84%, 72% to 86%, and 79% to 81% for the detection and 53% to 58%, 51% to 76%, and 49% to 55% for the classification of LSTV, respectively. CONCLUSION: Standard AP radiographs are insufficient to detect or classify LSTV. Coronal MRI scans, however, are highly reliable for classification of LSTV. PMID- 24210582 TI - Prostatic and renal aspergillosis due to Aspergillus fumigatus in a patient receiving alemtuzumab for chronic lymphocytic leukaemia. AB - OBJECTIVE: Treatment of chronic lymphocytic leukaemia (CLL) is rapidly evolving, with emerging new drugs. Alemtuzumab is a monoclonal antibody recognizing CD52 antigen approved in the treatment of relapsing-refractory CLL. A frequent side effect is the immunosuppression and patients treated with alemtuzumab risk to develop fungal infections such as aspergillosis. PATIENT AND METHODS: This case report is about a patient who developed an uncommon localization of aspergillosis: prostatic and renal, after a treatment by alemtuzumab monotherapy. During the week 8 of alemtuzumab, the patient presented fever, urinary frequency and urologic symptoms. Persistance of fever with common antibiotherapy led to realize a tomography that showed prostatic and renal abscess (70mm and 29mm). It was decided to realize a prostatic biopsy. RESULTS: Histological findings showed suppurative abscess with ischemic necrosis and fungal proliferation, with branched fungal hyphae. Direct examination was negative. Culture on Sabouraud's agar revealed a mould identified as Aspergillus fumigatus. The organism was susceptible to voriconazole (MIC: voriconazole 0,25ug/mL). CONCLUSION: Because of the main side effect of alemtuzumab is immunosuppression, we have to research fungal infections such as Aspergillosis, particularly in patients with fever resistant to common antibiotherapy. PMID- 24210583 TI - Chorioamnionitis and bronchopulmonary dysplasia in evolution. PMID- 24210584 TI - Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grades 1 or worse among 4215 Chinese women in a population-based study. AB - PURPOSE: To estimate the burden of human papillomavirus (HPV) infection and cervical disease among sexually active women in a sample of Chinese women. METHODS: A multicenter, population-based study was conducted between May 2006 and April 2007. A total of 4215 sexually active women aged 17-54 years were surveyed from five geographical sites representing both urban and rural areas: Beijing, Shanghai, Shanxi, Henan and Xinjiang. Women were referred for colposcopy on the basis of results of Pap testing and HPV screening. HPV genotyping of the CIN1+ specimens was performed with INNO-LiPA. Attribution of HPV types to lesions was estimated using a fractional contribution approach. RESULTS: 13.3% of the women (559/4215) were referred for colposcopy; 4.3% (183/4215) of these were diagnosed with CIN1+. Of the latter, 88.5% (162/183) were typed and 94.4% (153/162) were HPV-positive. HPV16 was the most prevalent type in lesions in both urban and rural settings. Combined, HPV16 and 18 were attributable to 71.4% of HPV-positive CIN2+ lesions. In addition, HPV31, 33, 52 and 58 were prevalent in CIN1+ lesions, with HPV33, 52, and 58 combined accounting for 24.1% CIN2+ lesions. Though prevalent, HPV31 always occurred as a co-infection with another HPV type and therefore was attributed minimal causality. CONCLUSIONS: HPV16 and 18 are associated with the majority of cervical lesions in Chinese women from which this population-based sample was drawn. In addition, other HPV types, such as 33, 52, and 58, also play an important role in cervical disease. PMID- 24210585 TI - Challenges of population-based colorectal cancer screening and the importance of time-trend analysis when evaluating system change. PMID- 24210586 TI - Glyoxal leads to defective keratinocyte migration and down-regulation of Snai2. PMID- 24210587 TI - Analysis and in vitro anti-Candida antifungal activity of Cuminum cyminum and Salvadora persica herbs extracts against pathogenic Candida strains. AB - OBJECTIVE: The in vitro antifungal activities of essential oil from Cuminum cyminum (C. cyminum) and alcoholic extract from Salvadora persica (S. persica) were investigated in order to evaluate their efficacy against C. albicans ATCC 14053, C. dubliniensis ATCC CD60, C. glabrata ATCC 90030, C. krusei ATCC 6258 and C. parapsilosis ATCC 22019. METHODS: The essential oil was obtained by hydrodistillation in a Clevenger apparatus and analyzed by gas chromatography/mass spectroscopy (GC/MS). The disc diffusion and broth macrodilution methods were used as antifungal susceptibility tests. RESULTS: The GC/MS analysis allowed 17 components to be determined; the main constituents of C. cyminum essential oil were alpha-pinene (30%), limonene (21%) and 1,8-cineole (18.5%). C. cyminum oil had a broad-spectrum antifungal activity against different pathogenic Candida species. Inhibition zone values ranged from 7 to 50mm for C. cyminum and 0 to 10mm for S. persica against the organisms tested. The best minimal inhibitory concentration (MIC) of C. cyminum oil was associated with C. albicans and C. dubliniensis (289 mg/L) and the MICs of S. persica extract were 4.9 mg/mL and 20mg/mL against C. albicans and C. dubliniensis, respectively. CONCLUSION: The results suggested the potential substitution of the antifungal chemicals by C. cyminum essential oil and S. persica alcoholic extract as natural inhibitors to control the growth of the most important pathogenic Candida species and alternative therapies for candidiasis. PMID- 24210588 TI - Relative energy balance, CKD, and risk of cardiovascular and all-cause mortality. AB - BACKGROUND: Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7 fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN: Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS: Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n = 2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS: Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60 mL/min/1.73 m(2). OUTCOMES: All-cause and cardiovascular mortality. MEASUREMENTS: All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS: 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60 mL/min/1.73 m(2) (n = 852), there was an increased risk of all-cause mortality (HR, 1.48; P = 0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P = 0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P = 0.04) and total sugars (HR per 100g/d, 1.62; P = 0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS: Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS: Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60 mL/min/1.73 m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events. PMID- 24210589 TI - Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. AB - A 20-year-old man was hospitalized for malignant hypertension, mechanical hemolysis, and kidney failure. Kidney biopsy confirmed glomerular and arteriolar thrombotic microangiopathy. Etiologic analyses, which included ADAMTS13 activity, stool culture, complement factor proteins (C3, C4, factor H, factor I, and MCP [membrane cofactor protein]), anti-factor H antibodies, HIV (human immunodeficiency virus) serology, and antinuclear and antiphospholipid antibodies, returned normal results. Malignant hypertension was diagnosed. Ten months later, we observed a relapse of acute kidney injury and mechanical hemolysis. Considering a diagnosis of complement dysregulation-related atypical hemolytic uremic syndrome (HUS), we began treatment with eculizumab. Despite the efficient complement blockade, the patient's kidney function continued to decline. We performed additional analyses and found that the patient's homocysteine levels were dramatically increased, with no vitamin B12 (cobalamin) or folate deficiencies. We observed very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. We stopped the eculizumab infusions and initiated specific treatment, which resulted in complete cessation of hemolysis. MMACHC (methylmalonic aciduria and homocystinuria type C protein) sequencing revealed compound heterozygosity for 2 causative mutations. To our knowledge, this is the first report of adult-onset cobalamin C-related HUS. Considering the wide availability and low cost of the homocysteine assay, we suggest that it be included in the diagnostic algorithm for adult patients who present with HUS. PMID- 24210590 TI - Estimated GFR decline as a surrogate end point for kidney failure: a post hoc analysis from the Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study and Irbesartan Diabetic Nephropathy Trial (IDNT). AB - BACKGROUND: A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defined by smaller declines in eGFR would improve the statistical power of these clinical trials. STUDY DESIGN: Post hoc analyses of 2 multinational randomized controlled trials (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan [RENAAL] and Irbesartan Diabetic Nephropathy Trial [IDNT]) that assessed the treatment effect of the angiotensin receptor blockers (ARBs) losartan and irbesartan. SETTING & PARTICIPANTS: 1,513 (RENAAL) and 1,715 (IDNT) adult patients with type 2 diabetes and nephropathy. PREDICTOR: Established versus alternative end points defined as a confirmed doubling of serum creatinine level versus confirmed eGFR decline of 57%, 40%, 30%, or 20% as a component of a composite end point of end-stage renal disease or eGFR < 15mL/min/1.73m(2). OUTCOMES: Numbers of patients reaching end points, precision (standard error), and significance (z score) of ARB treatment effect (HR) during follow-up. RESULTS: Lesser eGFR declines resulted in a greater number of patients reaching end points in both treatment groups and lower standard error of the HR, but the effect on z score was counterbalanced by attenuation of the HR. When calculating the eGFR decline from month 3, attenuation of the HR was less pronounced. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Despite increases in precision of the treatment effect, eGFR declines less than a doubling of serum creatinine value did not consistently improve statistical power of the clinical trials due to attenuation of the treatment effect. Attenuation of the treatment effect appears to be due in part to acute effects of ARBs on eGFR. These findings should be taken into account when using lesser eGFR declines as alternative end points for clinical trials. PMID- 24210591 TI - Survival trends in ESRD patients compared with the general population in the United States. AB - BACKGROUND: Health care resources expended on patients with end-stage renal disease (ESRD) have increased extensively, with uncertain changes in outcomes. In this study, we examined survival trends in the United States in patients with ESRD receiving renal replacement therapy with long-term dialysis or transplantation relative to the general population. STUDY DESIGN: Secondary analysis of records from the US Renal Data System. SETTING & PARTICIPANTS: American adults receiving renal replacement therapy in 1977, 1987, 1997, and 2007. PREDICTOR: Year. OUTCOME: 1-year survival. MEASUREMENTS: Abridged period life tables were created for each cross-sectional patient group and were compared with general US population life tables to measure relative survival, calculated as differences in average survival between the general US and the ESRD populations. RESULTS: From 1977 to 2007, ESRD patient groups became significantly older (mean age increased from 47 to 58 years) and sicker (ESRD due to diabetes increased from 9.1% to 38.2%; patients with a high death risk increased from 36.8% to 50.7%). Unadjusted age-specific survival improved (for 50-year-olds, average life expectancy increased 8% from 7.3 years in 1977 to 7.9 years in 2007), but age-specific survival increased more extensively in the general US population (from 27.5 years in 1977 to 30.9 years in 2007; 12% improvement). Accounting for this, age-specific relative survival in patients with ESRD decreased (for 50-year-olds, 20.2 life-years lost in 1977 vs 23.0 life-years lost in 2007). LIMITATIONS: Our analysis controlled for neither patient comorbid conditions nor initial glomerular filtration rate at the start of renal replacement therapy. CONCLUSIONS: Over the past 4 decades, age-specific survival in patients with ESRD has improved, but has not kept pace with that of the general US population. To be complete, future survival studies in patients with ESRD should focus on both temporal changes in survival within this group and changes relative to the general population. PMID- 24210592 TI - Surgical Oncology. Editorial. PMID- 24210593 TI - Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. AB - Before amyloid formation, peptides cleaved from the amyloid precursor protein (APP) exist as soluble oligomers. These are extremely neurotoxic. Their concentration is strongly correlated with synaptic impairment in animals and parallel cognitive decline in animals and humans. Clinical trials have largely been aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble load. Even treatment that should remove soluble oligomers has not consistently reduced the load. Failure to significantly improve cognition has frequently been attributed to failure of the amyloid hypothesis or to irreversible alteration in the brain. Instead, trial failures may be because of failure to significantly reduce load of toxic Abeta oligomers. Moreover, targeting only synthesis of Abeta peptides, only the oligomers themselves, or only the final insoluble amyloid may fail to significantly reduce soluble load because of the interrelationship between these 3 points in the amyloid cascade. Thus, treatments may fail unless trials target simultaneously all 3 points in the equation-"triple therapy". Cerebrospinal fluid analysis and other monitoring tools may in the future provide reliable measurement of soluble load. But currently, only analysis of autopsied brains can provide this data and thus enable proper evaluation and explanation of the outcome of clinical trials. These data are essential before attributing trial failures to the advanced nature of the disease or asserting that failures prove that the theory linking Alzheimer's disease to products of amyloid precursor protein is incorrect. PMID- 24210594 TI - Development of a model for predicting hydroxyl radical reaction rate constants of organic chemicals at different temperatures. AB - The reaction rate constants of hydroxyl radicals with organic chemicals (kOH) are of great importance for assessing the persistence and fate of organic pollutants in the atmosphere. However, experimental determination of kOH seems fairly unrealistic, due to the soaring number of the emerging chemicals additional to the large number of existing chemicals. Quantitative structure-activity relationship (QSAR) models are excellent choices for evaluating and predicting kOH values. In this study, a QSAR model that can predict kOH at different temperatures was developed by employing quantum chemical descriptors and DRAGON descriptors. The adjusted determination coefficient Radj(2) of the model is 0.873, and the external validation coefficient Qext(2) is 0.835, implying that the model has satisfactory robustness and good predictability. Additionally, a QSAR model was also built for kOH prediction at room-temperature (298 K). The development of the two models followed the guidelines for development and validation of QSAR models proposed by the Organization for Economic Co-operation and Development (OECD). The applicability domains of the current models were extended to several classes of compounds including long-chain alkenes (C8-C13), organophosphates, dimethylnaphthalenes, organic selenium and organic mercury compounds that have not been covered in the previous studies. PMID- 24210595 TI - Fe(III) reduction-mediated phosphate removal as vivianite (Fe3(PO4)2?8H2O) in septic system wastewater. AB - Phosphate is a water contaminant from fertilizers, soaps, and detergents that enters municipal and onsite wastewater from households, businesses, and other commercial operations. Phosphate is a limiting nutrient for algae, and is one of the molecules that promotes eutrophication of water bodies. Phosphate is especially problematic in onsite wastewater because there are few removal mechanisms under normal operating conditions; a system must be amended specifically with compounds to bond to or adsorb phosphate in the septic tank or within the leach field. Vivianite (Fe3(PO4)2?8H2O) is a stable mineral formed from ferrous iron and phosphate, often as the result of Fe(III) reducing microbial activity. What was unknown was the concentration of phosphate that could be removed by this process, and whether it was relevant to mixed microbial systems like septic tank wastewater. Data presented here demonstrate that significant concentrations of phosphate (12-14mM) were removed as vivianite in growing cultures of Geobacter metallireducens strain GS-15. Vivianite precipitates were identified on the cell surfaces and within multi cell clusters using TEM-EDX; the mineral phases were directly characterized using XRD. Phosphate was also removed in dilute and raw (undiluted) septic wastewater amended with different forms of Fe(III) including solid phase and soluble Fe(III). Vivianite precipitates were recovered and identified using XRD, along with siderite (ferrous carbonate), which was expected given that the systems were likely bicarbonate buffered. These data demonstrate that ferric iron amendments in septic wastewater increase phosphate removal as the mineral vivianite, and this may be a good strategy for phosphate attenuation in the septic tank portion of onsite wastewater systems. PMID- 24210596 TI - Atmospheric burden of organochlorine pesticides in Ghana. AB - Organochlorine pesticides (OCPs) are subject to the Stockholm Convention on POPs and have been banned or restricted globally. In Ghana, concerns of illicit applications of some OCPs have been raised in recent times. Applying polyurethane foam (PUF) disk passive air samplers (PAS), the levels of OCPs in the atmosphere and their spatial resolution were investigated. It was the first nationwide coverage of OCPs monitoring in Ghana. ?DDTs and endusulfans constituted the highest burden of atmospheric OCPs in Ghana, at average concentrations of 156+/ 36 and 153+/-28 pg m(-3), respectively. Mirex had the lowest concentration (0.2+/ 0.01 pg m(-3)). From the chemical signatures of the various OCPs, we deduced that DDT, endosulfans and heptachlor were freshly applied at certain sites, which were all agricultural sites. The OCPs were spatially resolved as a function of the types of crops cultivated in different areas, legacy issues and recent applications. PMID- 24210597 TI - Dynamics of transformation of the veterinary antibiotic sulfadiazine in two soils. AB - Veterinary antibiotics administered to livestock can be unintentionally released into the environment, for example by the application of manure to soils. The fate of such antibiotics in soils is mostly determined by sorption and degradation processes, including transformation. There is a need to further examine the combined transformation and sorption behavior of these emerging pollutants in soils. Long-term batch sorption experiments with the (14)C-radiolabeled antibiotic sulfadiazine enabled us to simultaneously trace the sorption and transformation dynamics of sulfadiazine. The parent compound and the transformation products were analyzed in the liquid phase and in the extracts from the solid phase after a sequential extraction. We found that of up to six transformation products were formed during degradation and that these products exhibited quite different dynamics in the two soils. Transformation products were formed rapidly and were extractable from the solid phase. We observed identical sets of the transformation products in both phases. The input concentration influenced the course of transformation of the parent substance. We present a detailed analysis including a mathematical description and derive regulatory kinetic endpoints for predicting environmental concentrations. PMID- 24210598 TI - Sediment baseline study of levels and sources of polycyclic aromatic hydrocarbons and heavy metals in Lake Nicaragua. AB - Selected metals and polycyclic aromatic hydrocarbons (PAHs) were analyzed in sediment samples from 24 sites in Lake Nicaragua sampled May 2010 to provide a baseline of pollution levels. Cu exceeded the Consensus-Based Sediment Quality Guideline (CBSQG) Threshold Effect Concentrations (TECs) at 21 sites while Ni exceeded the value at one site. Comparison of the sampling sites showed that the south-eastern shore and a central part of the lake contained the highest levels of As, Cd, Cr, and Ni, while the western part of the lake contained the highest levels of Cu, Pb, and Zn. Analysis of PAH levels showed that the CBSQG TECs were exceeded by naphthalene at five sites. The sum concentrations of the 16 US EPA priority PAHs (?PAH16) ranged from 0.01 mg kg(-1) dw to 0.64 mg kg(-1) dw. The highest ?PAH16 concentration was found upstream in River Mayales and the PAH composition revealed a heavy PAH fraction (e.g., creosote). The main sources of PAHs in Lake Nicaragua were determined as of diffuse petrogenic and pyrogenic origin as well as diagenetic produced perylene. The relative importance of these PAH sources was determined by interpretation of loading and score plots from a principal component analysis. This study concluded that areas of Lake Nicaragua represent an important pollution baseline for future studies in this lake and other tropical lakes. PMID- 24210599 TI - Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? AB - Dasatinib is a second generation tyrosine kinase inhibitor approved for clinical use in first line and imatinib-resistant chronic myeloid leukemia and Philadelphia positive (Ph+) acute lymphoblastic leukemia. In addition to BCR ABL1, dasatinib inhibits TEC kinases and SRC family kinases and is more potent than imatinib in the treatment of Ph+ leukemias. In the last 3 years, increases in cytotoxic T and natural-killer cells in peripheral blood samples have been reported in cases treated by dasatinib. The awareness of the clonal expansion of large granular lymphocytes and beneficial effect of these clonal cells increased the interest to dasatinib in cases receiving this drug. Clonal expansion of large granular lymphocytes is an important effect of dasatinib therapy, shown to be an off-target phenomenon associated with pleural effusion and better clinical response. The benefit of dasatinib-induced lymphocytosis and its underlying mechanism of this are important points for clinicians working in hematology and oncology. PMID- 24210600 TI - The effect of continuous positive airway pressure therapy on arterial stiffness and endothelial function in obstructive sleep apnea: a randomized controlled trial in patients without cardiovascular disease. AB - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality which may be mediated by increased arterial stiffness and endothelial dysfunction. Continuous positive airway pressure (CPAP) therapy improves excessive daytime somnolence (EDS), but its effect on vascular function in patients without preexisting cardiovascular disease (CVD) is unclear. METHODS: Fifty-three patients with OSA defined as an apnea-hypopnea index (AHI) of ?15 and without CVD were recruited into a double blind, randomized, placebo-controlled, crossover trial of 12weeks of CPAP therapy, of whom 43 participants completed the study protocol. Arterial stiffness was assessed by measuring the augmentation index (AIx) and pulse wave velocity (PWV) by applanation tonometry and cardiovascular magnetic resonance imaging to determine aortic distensibility. Endothelial function was assessed by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. RESULTS: CPAP therapy lowered systolic blood pressure (SBP) (126mmHg [standard deviation {SD}, 12] vs 129mmHg [SD, 14]; P=.03), with a trend towards reduced AIx (15.5 [SD, 11.9] vs 16.6 [SD, 11.7]%; P=.08) but did not modify endothelial function. When subjects with (n=24) and without (n=19) EDS were separately examined, no effect of CPAP therapy on vascular function was seen. CONCLUSIONS: In patients without overt CVD, CPAP therapy had a nonsignificant effect on AIx and did not modify endothelial function. PMID- 24210601 TI - Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece. AB - BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an uncontrolled need to move extremities accompanied by unpleasant sensations, which frequently leads to sleep disturbances. In hemodialysis (HD) patients, the previously reported RLS prevalence varied enormously, between 6% and 60%. In our study, we investigated the RLS prevalence in HD patients for the first time in Greece. METHODS: A continuous sample of HD patients was studied between January and September of 2010 in six dialysis units in Greece. RLS diagnosis was based on the essential clinical criteria of the International RLS Study Group (IRLSSG). The standardized incidence ratio (SIR) for RLS in HD patients was calculated in comparison to data from a recent survey of the general population in Greece. RESULTS: In our study of 579 HD patients in Greece (236 women; mean age, 65+/ 13years), the prevalence of RLS was elevated in comparison to the general population (26.6% vs 3.9%), with an SIR of 5.4 (95% confidence interval [CI], 4.6 6.3). In the fully adjusted model, the risk for RLS in HD patients was reduced in older age (odds ratio [OR], 0.98 [95% CI, 0.96-0.99]) and increased in women (OR, 1.60 [95% CI, 1.05-2.43]) in cases with elevated levels of beta2 microglobulin (OR, 1.15 [95% CI, 1.01-1.32]) and intact parathormone (iPTH) (OR, 1.30 [95% CI, 1.08-1.56]). CONCLUSION: A high RLS prevalence was recorded in a large HD population in Greece, clearly suggesting the need for enhanced awareness of RLS in nephrology. The RLS risk was increased in women and in younger HD patients as well as in those with elevated beta2 microglobulin and iPTH levels. PMID- 24210602 TI - Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia. AB - BACKGROUND: Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might induce or exacerbate periodic limb movements during sleep (PLMS). However, most of these studies were retrospective and cross sectional studies with small sample sizes on a selective SSRI, fluoxetine. Because different SSRIs have different pharmacologic profiles, it was not certain if other SSRIs also might lead to PLMS. METHODS: Data were taken from an open label 8-week trial of sertraline in depressive patients with insomnia (n=31). Depressed patients were administered sertraline 50mg at 8:00am on the first day, and the dosage was subsequently titrated up to a maximum of 200mg daily during the 8-week trial. All participants were tested by repeated polysomnography (PSG) (baseline, first day, 14th day, 28th day, and 56th day). Periodic leg movements (PLM) were visually counted and the PLM index (PLMI) was calculated. PLMS was defined as PLMI ?5, and significant PLMS was defined as PLMI ?15. RESULTS: Compared with baseline (PLMI, 3.6+/-1.5), all PLMI indices increased on the immediate administration of sertraline on the first day (PLMI, 5.1+/-3.9). From the 14th day onward, PLMI became stable and significantly higher than baseline and the first day (8.7+/-3.1 on the 14th day, 8.3+/-3.7 on the 28th day, and 8.5+/-3.6 on the 56th day; F[11.81]; P=.003). The clinical responses and PSG characteristics continuously improved during the 8-week trial. The PLMS group (PLMI ?5) had a higher arousal index (AI) than the non-PLMS group on the 14th day (9.4+/-5.5 vs 5.2+/-3.7; t test, 4.22; P=.03) and the 56th day (8.1+/-5.5 vs 4.3+/-3.7; z score, 3.11; P=.04); albeit, there was no significant clinical disturbances in the PLMS group. CONCLUSIONS: PLMS were increased during sertraline treatment, but only a few of the PLMS reached the significant level. This effect of sertraline on PLMS might be dosage dependent. Although the sertraline-induced PLMS did not seem to cause significant clinical disturbance, the PLMS group (PLMI ?5) had a higher AI than the non-PLMS group. Thus clinicians should pay more attention to PLMS during SSRI antidepressant treatment. PMID- 24210603 TI - Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis. AB - BACKGROUND: The prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea. METHODS: Our study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists. RESULTS: Of the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P=.042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06+/-8.43years vs 62.46+/-11.05years; P=.049) and had higher pain scores (visual analog scale [VAS], 4.69+/-2.52 vs 2.72+/-2.12; P=.002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF 36]) showed no significant difference between the two groups. CONCLUSIONS: The prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy. PMID- 24210604 TI - Insomnia in chronic obstructive pulmonary disease: breathless and sleepless. PMID- 24210605 TI - Psychopathologic correlates of adult sleepwalking. AB - OBJECTIVES: Sleepwalking (SW) often has been associated with psychopathology, but the nature and magnitude of this relation remains unclear. The aim of our study was to investigate the presence of psychopathology in a large cohort of sleepwalkers and to determine if levels of psychopathology showed differential relations to specific characteristics of the disorder, including clinical history. METHODS: One-hundred and five sleepwalkers (39 men, 66 women; mean age, 32.4+/-9.5years) referred to our sleep disorders clinic for chronic SW underwent a comprehensive clinical investigation that included an overnight polysomnography (PSG) assessment in 90% of cases. All participants also completed a series of questionnaires, including the Beck Depression Inventory, Second Revision (BDI II), the Beck Anxiety Inventory (BAI), and the Symptom Checklist 90-Revised (SCL 90-R). RESULTS: The proportion of sleepwalkers who scored above the minimal clinical threshold on the BDI-II, BAI, and SCL-90-R was 27%, 40%, and 28%, respectively. Only 15% of sleepwalkers showed moderate to severe symptoms on the BDI-II and 19% on the BAI. Taken as a whole, these profiles are similar to those observed in the general adult population. The presence of psychopathology in sleepwalkers was associated with a negative family history for SW, a higher frequency of nightmares, and with potentially injurious behaviors enacted during somnambulistic episodes. CONCLUSIONS: A majority of adult sleepwalkers consulting for the disorder do not report clinically significant levels of depression or anxiety. Overall, sleepwalkers with and without psychopathology appear more similar than dissimilar. PMID- 24210606 TI - The effect of childhood obstructive sleep apnea on ambulatory blood pressure is modulated by the distribution of respiratory events during rapid eye movement and nonrapid eye movement sleep. AB - OBJECTIVE: We aimed to investigate if different childhood obstructive sleep apnea (OSA) subtypes, namely rapid eye movement (REM)-related, nonrapid eye movement (NREM)-related and stage-independent OSA would exert different effects on ambulatory blood pressure (ABP). METHODS: Data from our previous school-based cross-sectional study were reanalyzed. Subjects who had an obstructive apnea hypopnea index (OAHI) between 1 and 10 events per hour and a total REM sleep duration of >30min were included in our analysis. REM-related and NREM-related OSA were defined as a ratio of OAHI in REM sleep (OAHIREM) to OAHI in NREM sleep (OAHINREM) of >2 and <0.5, respectively. The others were classified as stage independent OSA. RESULTS: A total of 162 subjects were included in the analysis. In the mild OSA (OAHI, 1-5events/h) subgroup, no significant differences in any ABP parameters were found between OSA subtypes. On the other hand, in subjects with moderate OSA (OAHI, 5-10events/h), the REM-related OSA subtype had a significantly lower daytime systolic blood pressure (SBP) z score (-0.13+/-0.90 cf 1.15+/-0.67; P=.012) and nighttime SBP z score (0.29+/-1.06 cf 1.48+/-0.88, P=.039) than the stage-independent OSA subtype. Linear regression analyses revealed that OAHINREM but not OAHIREM was significantly associated with both daytime (P=.008) and nighttime SBP (P=.042) after controlling for age, gender, and body size. CONCLUSION: Children with obstructive events mainly in REM sleep may have less cardiovascular complications than those with stage-independent OSA. PMID- 24210607 TI - Let there be no light: the effect of bedside light on sleep quality and background electroencephalographic rhythms. AB - OBJECTIVES: Artificial lighting has been beneficial to society, but unnecessary light exposure at night may cause various health problems. We aimed to investigate how whole-night bedside light can affect sleep quality and brain activity. PATIENTS AND METHODS: Ten healthy sleepers underwent two polysomnography (PSG) sessions, one with the lights off and one with the lights on. PSG variables related to sleep quality were extracted and compared between lights-off and lights-on sleep. Spectral analysis was performed to rapid eye movement (REM) sleep and non-REM (NREM) sleep epochs to reveal any light-induced differences in background brain rhythms. RESULTS: Lights-on sleep was associated with increased stage 1 sleep (N1), decreased slow-wave sleep (SWS), and increased arousal index. Spectral analysis revealed that theta power (4-8Hz) during REM sleep and slow oscillation (0.5-1Hz), delta (1-4Hz), and spindle (10-16Hz) power during NREM sleep were decreased in lights-on sleep conditions. CONCLUSIONS: Sleeping with the light on not only causes shallow sleep and frequent arousals but also has a persistent effect on brain oscillations, especially those implicated in sleep depth and stability. Our study demonstrates additional hazardous effect of light pollution on health. PMID- 24210608 TI - Oculomasticatory myorhythmia and agrypnia excitata guide the diagnosis of Whipple disease. PMID- 24210609 TI - The effect of continuous positive airway pressure therapy on vascular function in obstructive sleep apnea: how much is enough? PMID- 24210611 TI - A series of Mousterian occupations in a new type of site: the Nesher Ramla karst depression, Israel. AB - We report the discovery of a new type of hominin site in the Levant, inhabited during MIS 6-5. The site, found within a karst depression at Nesher Ramla, Israel, provides novel evidence for Middle Paleolithic lifeways in an environmental and depositional setting that is previously undocumented in the southern Levant. The carbonate bedrock in the area is characterized by surface depressions formed by gravitational sagging of the rock into underlying karst voids. In one such depression, an 8 m thick sequence comprising rich and well preserved lithic and faunal assemblages, combustion features, hundreds of manuports and ochre was discovered. Here we focus on the geological and environmental setting and present optically stimulated luminescence (OSL) ages for the 8 m sequence, aiming to place the site within a firm chronological framework and determine its significance for a more complete reconstruction of cultural developments in the Levantine Middle Paleolithic. To that end, preliminary results of the lithic and faunal studies are also presented. PMID- 24210610 TI - Nephron-sparing surgery for renal tumors measuring more than 7 cm: morbidity, and functional and oncological outcomes. AB - BACKGROUND: The purpose of this study was to evaluate morbidity, functional, and oncological outcomes after NSS in renal tumors > 7 cm. MATERIALS AND METHODS: We retrospectively analyzed data from 168 patients with tumors > 7 cm who were treated using NSS between 1998 and 2012. RESULTS: Imperative and elective indications accounted for 76 (45.2%) and 92 (54.8%) patients, respectively. Major perioperative complications and renal function deterioration occurred in 33 (19.6%) and 51 patients (30.4%), respectively. In multivariate analysis, age older than 60 years (P = .001; hazard ratio [HR], 5) and tumor malignancy (P = .014; HR, 6.7) were prognostic factors for renal function deterioration whereas imperative indication was a risk factor for major postoperative complications (P = .0019; HR, 2.7). In 126 (75%) patients with malignant tumors, after a median follow-up of 30 months (range, 1-254 months), 25 patients (20.2%) died. In multivariate analysis, imperative indication (P = .023; HR, 4.2), positive surgical margin (P = .021; HR, 3.3), and Fuhrman grade > II (P = .013; HR, 3.7) were prognostic indicators for cancer-free survival (CFS). Imperative indication (P = .04; HR, 8.5) and Fuhrman grade > II (P = .04; HR, 3.9) were predictive factors of cancer-specific survival (CSS). In case of elective indication, positive surgical margin, local recurrence, and cancer-related death occurred in 4 (7.6%), 1 (1.1%), and 1 (1.1%) cases, respectively. For elective indication, 5 year estimates of CFS, CSS, and overall survival rates were: 85.7%, 98%, and 93.9%, respectively. CONCLUSION: In this selected population, imperative vs. elective indication status seems to play a critical role in oncologic outcomes. Oncologic results for elective indications are close to those reported with radical nephrectomy. PMID- 24210612 TI - Mutation, condition, and the maintenance of extended lifespan in Drosophila. AB - The evolutionary theory of aging predicts that longevity will decline via drift or age-specific tradeoffs when selection favors early life fitness. Many Drosophila melanogaster populations continually terminated at young adult ages retain surprisingly long postselection lifespans. We compiled three decades of longevity data from the Ives population, demonstrating that postselective longevity was both substantial (30 days) and temporally stable over this period. Recently, alleles with positive pleiotropic effects between adjacent ages, particularly those affecting overall condition, have been integrated into the theory and may explain the extended longevity observed. We experimentally tested this hypothesis by isolating 20 hemiclones from Ives and allowing spontaneous mutations to accumulate (MA) for 35 generations. Fitness and longevity were positively genetically correlated in control females, and both traits declined due to MA. Crucially, MA induced a strong positive genetic correlation between the traits in both sexes, implying that mutations with early-life impacts also reduce late-life survival. Our results suggest that extended postreproductive longevity is actively maintained by selection for early-life fitness via positive pleiotropy and is not a merely a byproduct of exhaustion of genetic variation or weak drift. Thus mutation-selection balance for early fitness may govern variance in longevity in this system: a balance struck remarkably long after selection for continued survival ceases. PMID- 24210613 TI - A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. AB - BACKGROUND: The class V POU domain transcription factor Oct4 (Pou5f1) is a pivotal regulator of embryonic stem cell (ESC) self-renewal and reprogramming of somatic cells to induced pluripotent stem (iPS) cells. Oct4 is also an important evolutionarily conserved regulator of progenitor cell differentiation during embryonic development. RESULTS: Here we examine the function of Oct4 homologs in Xenopus embryos and compare this to the role of Oct4 in maintaining mammalian embryo-derived stem cells. Based on a combination of expression profiling of Oct4/POUV-depleted Xenopus embryos and in silico analysis of existing mammalian Oct4 target data sets, we defined a set of evolutionary-conserved Oct4/POUV targets. Most of these targets were regulators of cell adhesion. This is consistent with Oct4/POUV phenotypes observed in the adherens junctions in Xenopus ectoderm, mouse embryonic, and epiblast stem cells. A number of these targets could rescue both Oct4/POUV phenotypes in cellular adhesion and multipotent progenitor cell maintenance, whereas expression of cadherins on their own could only transiently support adhesion and block differentiation in both ESC and Xenopus embryos. CONCLUSIONS: Currently, the list of Oct4 transcriptional targets contains thousands of genes. Using evolutionary conservation, we identified a core set of functionally relevant factors that linked the maintenance of adhesion to Oct4/POUV. We found that the regulation of adhesion by the Oct4/POUV network occurred at both transcriptional and posttranslational levels and was required for pluripotency. PMID- 24210614 TI - The mechanism of kindlin-mediated activation of integrin alphaIIbbeta3. AB - Increased ligand binding to cellular integrins ("activation") plays important roles in processes such as development, cell migration, extracellular matrix assembly, tumor metastasis, hemostasis, and thrombosis. Integrin activation encompasses both increased integrin monomer affinity and increased receptor clustering and depends on integrin-talin interactions. Loss of kindlins results in reduced activation of integrins. Kindlins might promote talin binding to integrins through a cooperative mechanism; however, kindlins do not increase talin association with integrins. Here, we report that, unlike talin head domain (THD), kindlin-3 has little effect on the affinity of purified monomeric alphaIIbbeta3, and it does not enhance activation by THD. Furthermore, studies with ligands of varying valency show that kindlins primarily increase cellular alphaIIbbeta3 avidity rather than monomer affinity. In platelets or nucleated cells, loss of kindlins markedly reduces alphaIIbbeta3 binding to multivalent but not monovalent ligands. Finally, silencing of kindlins reduces the clustering of ligand-occupied alphaIIbbeta3 as revealed by total internal reflection fluorescence and electron microscopy. Thus, in contrast to talins, kindlins have little primary effect on integrin alphaIIbbeta3 affinity for monovalent ligands and increase multivalent ligand binding by promoting the clustering of talin activated integrins. PMID- 24210615 TI - Msn2 coordinates a stoichiometric gene expression program. AB - BACKGROUND: Many cellular processes operate in an "analog" regime in which the magnitude of the response is precisely tailored to the intensity of the stimulus. In order to maintain the coherence of such responses, the cell must provide for proportional expression of multiple target genes across a wide dynamic range of induction states. Our understanding of the strategies used to achieve graded gene regulation is limited. RESULTS: In this work, we document a relationship between stress-responsive gene expression and the transcription factor Msn2 that is graded over a large range of Msn2 concentrations. We use computational modeling and in vivo and in vitro analyses to dissect the roots of this relationship. Our studies reveal a simple and general strategy based on noncooperative low-affinity interactions between Msn2 and its cognate binding sites as well as competition over a large number of Msn2 binding sites in the genome relative to the number of Msn2 molecules. CONCLUSIONS: In addition to enabling precise tuning of gene expression to the state of the environment, this strategy ensures colinear activation of target genes, allowing for stoichiometric expression of large groups of genes without extensive promoter tuning. Furthermore, such a strategy enables precise modulation of the activity of any given promoter by addition of binding sites without altering the qualitative relationship between different genes in a regulon. This feature renders a given regulon highly "evolvable." PMID- 24210616 TI - A glutamate-dependent redox system in blood cells is integral for phagocytosis in Drosophila melanogaster. AB - Glutamate transport is highly regulated as glutamate directly acts as a neurotransmitter and indirectly regulates the synthesis of antioxidants. Although glutamate deregulation has been repeatedly linked to serious human diseases such as HIV infection and Alzheimer's, glutamate's role in the immune system is still poorly understood. We find that a putative glutamate transporter in Drosophila melanogaster, polyphemus (polyph), plays an integral part in the fly's immune response. Flies with a disrupted polyph gene exhibit decreased phagocytosis of microbial-derived bioparticles. When infected with S. aureus, polyph flies show an increase in both susceptibility and bacterial growth. Additionally, the expression of two known glutamate transporters, genderblind and excitatory amino acid transporter 1, in blood cells affects the flies' ability to phagocytose and survive after an infection. Consistent with previous data showing a regulatory role for glutamate transport in the synthesis of the major antioxidant glutathione, polyph flies produce more reactive oxygen species (ROS) as compared to wild-type flies when exposed to S. aureus. In conclusion, we demonstrate that a polyph-dependent redox system in blood cells is necessary to maintain the cells' immune-related functions. Furthermore, our model provides insight into how deregulation of glutamate transport may play a role in disease. PMID- 24210618 TI - Compartmentalized calcium signaling in cilia regulates intraflagellar transport. AB - Intraflagellar transport (IFT) underpins many of the important cellular roles of cilia and flagella in signaling and motility. The microtubule motors kinesin-2 and cytoplasmic dynein 1b drive IFT particles (protein complexes carrying ciliary component proteins) along the axoneme to facilitate the assembly and maintenance of cilia. IFT is regulated primarily by cargo loading onto the IFT particles, although evidence suggests that IFT particles also exhibit differential rates of movement. Here we demonstrate that intraflagellar Ca(2+) elevations act to directly regulate the movement of IFT particles. IFT-driven movement of adherent flagella membrane glycoproteins in the model alga Chlamydomonas enables flagella mediated gliding motility. We find that surface contact promotes the localized accumulation of IFT particles in Chlamydomonas flagella. Highly compartmentalized intraflagellar Ca(2+) elevations initiate retrograde transport of paused IFT particles to modulate their accumulation. Gliding motility induces mechanosensitive intraflagellar Ca(2+) elevations in trailing (dragging) flagella only, acting to specifically clear the accumulated microtubule motors from individual flagella and prevent a futile tug-of-war. Our results demonstrate that compartmentalized intraciliary Ca(2+) signaling can regulate the movement of IFT particles and is therefore likely to play a central role in directing the movement and distribution of many ciliary proteins. PMID- 24210619 TI - Trends in applications for thoracic fellowship in comparison with other subspecialties. AB - BACKGROUND: Length of training (LOT), lifestyle, and decreasing reimbursement have been credited with contributing to the decline in applications to thoracic surgery (TS). Other surgical specialties share similarities in LOT and lifestyle; however, trends in applications for these specialties have not been compared. One cannot look at applications to TS without examining concurrent changes in the pool of residents finishing general surgery. To clarify the relative impact of LOT, lifestyle, applicant pool, and reimbursement on applications to TS, we analyzed these trends concurrently. METHODS: National Resident Matching Program residency and fellowship match placement data (1997 to 2012) for general, TS, pediatric, transplant, and vascular surgery, including integrated TS and vascular surgery, were analyzed. Corresponding trends in reimbursement were analyzed from Medical Group Management Association data (1996 to 2010). RESULTS: During the study period, percentage of medical students matching into general surgery has remained relatively constant (4.9% to 5.5%). Applications for TS have declined since 1997. Applications for pediatric and transplant surgery have increased. Vascular surgery has remained relatively constant, with an applicant to position ratio approximately 1:1. Integrated programs (thoracic and vascular) have been popular; 3 to 7.4 applicants per position and 2 to 3.47 applicants per position, respectively. Cardiovascular surgery median salaries have remained largely the same; salaries for general thoracic, pediatric, transplant, and vascular surgery have increased (1.95% to 7.13% per year) although cardiovascular surgeons continue to have the highest median salary. CONCLUSIONS: Given the above data, it does not appear that LOT is the critical issue associated with the decline in fellowship applications for TS. The increased demand for integrated training programs may be reflective of other factors rather than LOT. The success of abbreviated programs in training competent thoracic surgeons has not yet been determined. Given that LOT does not appear to affect applications to surgical specialty, we may be able to maintain applications to the specialty without compromising LOT. PMID- 24210617 TI - Circadian yin-yang regulation and its manipulation to globally reprogram gene expression. AB - BACKGROUND: The cyanobacterial circadian program exerts genome-wide control of gene expression. KaiC undergoes rhythms of phosphorylation that are regulated by interactions with KaiA and KaiB. The phosphorylation status of KaiC is thought to mediate global transcription via output factors SasA, CikA, LabA, RpaA, and RpaB. Overexpression of kaiC has been reported to globally repress gene expression. RESULTS: Here, we show that the positive circadian component KaiA upregulates "subjective dusk" genes and that its overexpression deactivates rhythmic gene expression without significantly affecting growth rates in constant light. We analyze the global patterns of expression that are regulated by KaiA versus KaiC and find in contrast to the previous report of KaiC repression that there is a "yin-yang" regulation of gene expression whereby kaiA overexpression activates "dusk genes" and represses "dawn genes," whereas kaiC overexpression complementarily activates dawn genes and represses dusk genes. Moreover, continuous induction of kaiA latched KaiABC-regulated gene expression to provide constitutively increased transcript levels of diverse endogenous and heterologous genes that are expressed in the predominant subjective dusk phase. In addition to analyzing KaiA regulation of endogenous gene expression, we apply these insights to the expression of heterologous proteins whose products are of potential value, namely human proinsulin, foreign luciferase, and exogenous hydrogenase. CONCLUSIONS: Both KaiC and KaiA complementarily contribute to the regulation of circadian gene expression via yin-yang switching. Circadian patterns can be reprogrammed by overexpression of kaiA or kaiC to constitutively enhance gene expression, and this reprogramming can improve 24/7 production of heterologous proteins that are useful as pharmaceuticals or biofuels. PMID- 24210620 TI - Stented elephant trunk technique for retrograde type A aortic dissection after endovascular stent graft repair. AB - BACKGROUND: Retrograde type A aortic dissection is a rare but deadly complication after thoracic endovascular aortic repair of type B aortic dissection. Total arch replacement combined with a modified stented elephant trunk technique (SET), was performed for these complicated dissections. We reviewed our results of the procedure for this serious complication, aiming to evaluate the feasibility of the technique. METHODS: Between April 2005 and September 2012, 24 patients with retrograde type A aortic dissection after thoracic endovascular aortic repair underwent the SET procedure in our center. The mean age at operation was 44.1+/ 8.8 years old. Postoperative mortality and morbidity were analyzed to evaluate the immediate and mid-term results. RESULTS: Death at 30 days was 4.2% (1 of 24 patients). No patient suffered paraplegia or stroke after operation. Follow-up was completed with 23 survivors. The mean follow-up period was 32.2+/-13.1 months (range, 12 to 49 months). No late deaths occurred during follow-up. One patient underwent reoperation for replacement of the thoracoabdominal aorta and enjoyed an uneventful survival. CONCLUSIONS: The stented elephant trunk technique could be an alternative for treatment of retrograde type A aortic dissection with acceptable surgical risks and satisfactory results. PMID- 24210621 TI - Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients. AB - BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest. The exact complication rate is not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates for ECMO. METHODS: A systematic PubMed search was conducted on ECMO for treatment of cardiogenic shock or cardiac arrest in adult patients only, updated to November 2012. Studies with more than 10 patients published in the year 2000 or later that reported complication rates for ECMO were included. Specific complications analyzed included lower extremity ischemia, fasciotomy or compartment syndrome, amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection. For studies that included overlapping patients, the largest study was included and the others excluded. Cochran's Q and I-squared were calculated. A more conservative random-effects model was chosen for all analyses. RESULTS: Twenty studies were included in the analyses encompassing 1,866 patients. Seventeen studies reported survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Analyses encompassed 192 to 1,452 patients depending on the specific complication analyzed. The pooled estimate rates of complications with 95% confidence intervals were as follows: lower extremity ischemia, 16.9% (12.5% to 22.6%); fasciotomy or compartment syndrome, 10.3% (7.3% to 14.5%); lower extremity amputation, 4.7% (2.3% to 9.3%); stroke, 5.9% (4.2% to 8.3%); neurologic complications, 13.3% (9.9% to 17.7%); acute kidney injury, 55.6% (35.5% to 74.0%); renal replacement therapy, 46.0% (36.7% to 55.5%); major or significant bleeding, 40.8% (26.8% to 56.6%); rethoracotomy for bleeding or tamponade in postcardiotomy patients, 41.9% (24.3% to 61.8%); and significant infection, 30.4% (19.5% to 44.0%). CONCLUSIONS: Although ECMO can improve survival of patients with advanced heart disease, there is significant associated morbidity with performance of this intervention. These findings should be incorporated in the risk-benefit analysis when initiation of ECMO for cardiogenic shock is being considered. PMID- 24210622 TI - Posterior restoration of left ventricle and mitral valve repair in patients with muscular dystrophy. AB - BACKGROUND: Congestive heart failure (CHF) is major risk factor for survival among patients with muscular dystrophy (MD). The degenerative postero-lateral wall of the left ventricle (LV), which results in systolic dysfunction and functional mitral regurgitation (MR) at the time of CHF, is not well described in MD. METHODS: We restored the LV and repaired the mitral valves of 6 patients (mean age, 43 +/- 9 years) during emergency and elective procedures. Two and 4 patients were in New York Heart Association (NYHA) functional classes III and IV, respectively. One patient required emergency preoperative intraaortic balloon pump support. Before operation, speckle-tracking echocardiography was applied to detect the myocardial lesion. The postero-lateral LV wall that is critically affected in MD was excluded during posterior restoration. Functional MR was repaired using a combination of ring annuloplasty, papillary muscle approximation, and chordal cutting. The LV myocardium between the end of the LV incision line and the mitral annulus was cryoablated to prevent late ventricular arrhythmia. RESULTS: All patients survived (100%) for a mean follow-up of 59+/-39 (range; 5 to 101) months. The NYHA functional classes improved to I and II (n=3 each). Left ventricular end-diastolic diameter significantly decreased from 77+/ 13 to 59+/-4 mm (p=0.0088), whereas ejection fraction did not significantly improve (0.24+/-0.1 vs 0.29+/-0.11, p=0.2451), although MR severity was significantly eliminated (3.5+/-0.5 vs 0.5+/-0.6, p=0.0003). No cardiac events were associated with CHF or arrhythmia during follow-up. CONCLUSIONS: Posterior restoration of the LV and mitral repair are useful for treating CHF in patients with MD, and improve survival. PMID- 24210623 TI - Lifetime major depression and comorbid disorders among current-era women veterans. AB - BACKGROUND: Most research on women veterans' mental health has focused on postraumatic stress disorder (PTSD) or reactions to military sexual trauma. Although depression is also a frequent diagnosis among women veterans, little is known about its characteristics, including comorbid conditions and patterns of disorder onset. We investigated lifetime diagnoses of major depressive disorder (MDD) and comorbid conditions in a primarily treatment-seeking research sample of male and female veterans to determine frequency of lifetime MDD, comorbid disorders and their temporal onset. METHOD: The 1700 veterans (346 women; 1354 men) completed diagnostic interviews as participants in a research registry. Rates of and gender differences in lifetime MDD and comorbid conditions (PTSD, other anxiety disorders, substance use and eating disorders) were calculated. We assessed the percentage of cases in which MDD preceded the comorbid condition (primary onset MDD). RESULTS: Lifetime MDD was frequent in this sample, and significantly more common in women (46.5%) than in men (36.3%). Gender differences in comorbidity were found for anxiety and eating disorders (more common in women); and for alcohol and nicotine use disorders (more common in men). However, primary onset MDD was no more common among women than among men, and was in neither case the predominant pattern of comorbid lifetime disorder onset. LIMITATIONS: The sample is not representative of all veterans, and lifetime diagnoses were based on retrospective recall. CONCLUSIONS: MDD usually follows the onset of other comorbid disorders among women veterans, indicating the need to assess for earlier lifetime disorders in veterans with MDD. PMID- 24210624 TI - The prospective long-term course of adult depression in general practice and the community. A systematic literature review. AB - BACKGROUND: Findings about the prospective long-term course of depression are usually derived from clinical populations while knowledge about the course in community and primary care samples is rarer. As depressive disorders are highly prevalent and associated with considerable disability and costs, this information is needed to identify the percentages of subjects with a favorable or unfavorable prognosis. Therefore our aim was to summarize the available evidence on the prospective longitudinal course of depression in both general practice and the community. METHODS: We conducted a systematic, computerized search of Medline and PsycINFO. Main selection criteria were (a) adults with observer assessed depressive disorder recruited in the community or in general practice and (b) naturalistic study with follow-up length of at least three years. As primary outcome the percentages of stable recovery, recovery during or at follow-up, recurrence and chronic course were used. RESULTS: We identified 12 cohorts, with 4009 followed-up individuals. Follow-up intervals ranged between three and 49 years. Between 35% and 60% of participants experienced a stable recovery with no (further) recurrences, while 70-85% recovered at least once during follow-up. A consistent percentage of 10-17% had a chronic course. Recurrence rates varied considerably ranging between 7% and 65%. Significant predictors of an unfavorable course appear to be mainly those variables that lie within the course of depression itself, i.e. history of depression, baseline severity, and comorbidity. LIMITATIONS: Use of broad inclusion criteria heightened study heterogeneity and hampered comparability. CONCLUSION: Regarding stable recovery, the long-term course within general practice and community samples seems more favorable than within clinical samples. Further research applying a standardized methodology is required. PMID- 24210626 TI - Does obesity predict bipolarity in major depressive patients? AB - BACKGROUND: Differential association of obesity in bipolar and unipolar Major Depressive Episode (MDE) has not been systematically studied. We explore the relationships between obesity and history of manic and hypomanic symptoms in a large national clinical sample of MDE patients. METHOD: The sample comprised 571 consecutive patients with a DSM-IV diagnosis of MDE enrolled in a 7 months period. The study involved 30 psychiatric facilities for outpatients, distributed throughout Italy. Diagnosis was formulated by psychiatrists with extensive clinical experience in the diagnosis and treatment of mood disorders. In all patients height (meters) and weight (kilograms) were systematically measured at the moment of the clinical evaluation. The severity of depressive and anxious symptomatology was self-evaluated by the means of Zung's questionnaires for depression and anxiety. For the evaluation of lifetime manic or hypomanic features, Hypomania Check List-32 was also administered. Obese and Non-Obese subgroups were identified on the basis of a >30 BMI cut off point. RESULTS: BMI <=30 was observed in 86 (15.1%) of our MDE patients. The Obese and Non-Obese subgroups did not report differences as regards to age and gender distribution. Obese patients reported a lower number of years of education in comparison with Non-Obese patients. As regards to marital status, Obese patients were more frequently married in comparison with the Non-Obese patients. Obese patients were more frequently belonging to the bipolar group than Non-Obese patients. Obese subjects also reported more frequently than Non-Obese an HCL total score >14. The effect of educational level, marital status and bipolar-unipolar distinction on the probability of Obese group membership was analyzed by stepwise logistic regression. Bipolar subtype resulted to be the strongest predictor of Obesity. LIMITATIONS: Pharmacological treatments and co-morbidity with other psychiatric disorders are not explored and accounted for in our analyses. CONCLUSIONS: Obesity in our national sample of patients with MDE is associated with bipolar subtype and (hypo)manic symptoms. These findings suggest the possibility that the presence of obesity in patients with MDE might be related to bipolarity. A common impulsive-addictive diathesis is proposed as mediating mechanism. Further longitudinal studies in clinical and non-clinical populations are necessary to better define the burden and the role of the association between obesity and bipolarity. PMID- 24210625 TI - Improving the psychometric utility of the hypomania checklist (HCL-32): a Rasch analysis approach. AB - BACKGROUND: The HCL-32 is a widely-used screening questionnaire for hypomania. We aimed to use a Rasch analysis approach to (i) evaluate the measurement properties, principally unidimensionality, of the HCL-32, and (ii) generate a score table to allow researchers to convert raw HCL-32 scores into an interval level measurement which will be more appropriate for statistical analyses. METHODS: Subjects were part of the Bipolar Disorder Research Network (BDRN) study with DSM-IV bipolar disorder (n=389). Multidimensionality was assessed using the Rasch fit statistics and principle components analysis of the residuals (PCA). Item invariance (differential item functioning, DIF) was tested for gender, bipolar diagnosis and current mental state. Item estimates and reliabilities were calculated. RESULTS: Three items (29, 30, 32) had unacceptable fit to the Rasch unidimensional model. Item 14 displayed significant DIF for gender and items 8 and 17 for current mental state. Item estimates confirmed that not all items measure hypomania equally. LIMITATIONS: This sample was recruited as part of a large ongoing genetic epidemiology study of bipolar disorder and may not be fully representative of the broader clinical population of individuals with bipolar disorder. CONCLUSION: The HCL-32 is unidimensional in practice, but measurements may be further strengthened by the removal of four items. Re-scored linear measurements may be more appropriate for clinical research. PMID- 24210627 TI - Psychological coping in depressed outpatients: association with cortisol response to the combined dexamethasone/CRH test. AB - BACKGROUND: Depression is associated with dysfunctional coping styles and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. Studies have shown that maladaptive coping strategies relate to abnormal HPA axis function; however, such a relationship has been under-studied in patients with depression. We aimed to examine whether dysfunctional coping styles in depression would be associated with abnormal cortisol reactivity. METHODS: Seventy-four outpatients with major depressive disorder and 133 age- and sex-matched healthy individuals were recruited. Coping was assessed by the Ways of Coping Checklist. Psychological distress was assessed by the Hopkins Symptom Checklist. Cortisol reactivity was measured by the combined dexamethasone/corticotropin-releasing hormone test. RESULTS: Compared to healthy individuals, depressed patients demonstrated significantly less use of problem-solving, positive reappraisal and social support coping styles and more use of self-blame and wishful thinking styles. Such a pattern of coping styles was significantly associated with patients' greater distress. Partial correlation analysis in patients, controlling for age and sex, revealed a significant correlation between more use of escape avoidance coping and lower levels of reactive cortisol measures. A stepwise multiple regression analysis predicting cortisol reactivity from age, sex, distress, symptom severity and coping styles revealed that escape-avoidance coping was a significant predictor. LIMITATIONS: The neuroendocrine challenge test was administered only once, based on a simple test protocol. CONCLUSIONS: More use of escape-avoidance coping in depressed patients was associated with less cortisol reactivity. Our findings shed light on the heterogeneity of depression in terms of low and high levels of avoidance associated with exaggerated and blunted HPA axis reactivity, respectively. PMID- 24210629 TI - Unipolar mania: a distinct entity? AB - BACKGROUND: Whether or not unipolar mania is a separate nosological entity remains a subject of dispute. This review discusses that question in light of recent data. METHODS: Unipolar mania studies in the PUBMED database and relevant publications and cross-references were searched. RESULTS: There seems to be a bipolar subgroup with a stable, unipolar recurrent manic course, and that 15-20% of bipolar patients may be unipolar manic. Unipolar mania may be more common in females. It seems to have a slightly earlier age of illness onset, more grandiosity, psychotic symptoms, hyperthymic temperament, but less rapid-cycling, suicidality and comorbid anxiety disorders. It seems to have a better course of illness with better social and professional adjustment. However, its response to lithium prophylaxis seems to be worse, although its response to valproate is the same when compared to that of classical bipolar. LIMITATIONS: The few studies on the subject are mainly retrospective, and the primary methodological criticism is the uncertainty of the diagnostic criteria for unipolar mania. CONCLUSIONS: The results indicate that unipolar mania displays some different clinical characteristics from those of classical bipolar disorder. However, whether or not it is a separate nosological entity has not been determined due to the insufficiency of relevant data. Further studies with standardized diagnostic criteria are needed. Considering unipolar mania as a course specifier of bipolar disorder could be an important step in this respect. PMID- 24210628 TI - Dimensions in major depressive disorder and their relevance for treatment outcome. AB - BACKGROUND: Major depressive disorder (MDD) is a heterogeneous disease. More homogeneous psycho(patho)logical dimensions would facilitate MDD research as well as clinical practice. The first aim of this study was to find potential dimensions within a broad psychopathological assessment in depressed patients. Second, we aimed at examining how these dimensions predicted course in MDD. METHODS: Ten psychopathological variables were assessed in 75 MDD inpatients. Factor and regression analyses assessed putative relations between psychopathological factors and depression severity and outcome after 8 weeks of treatment. RESULTS: A 3-factor model (eigenvalue: 54.4%) was found, representing a psychomotor change, anhedonia and negative affect factor. Anhedonia and negative affect predicted depression severity (R(2)=0.37, F=20.86, p<0.0001). Anhedonia predicted non-response (OR 6.00, CI 1.46-24.59) and both negative affect (OR 5.69, CI 1.19-27.20) and anhedonia predicted non-remission (OR 9.28, CI 1.85-46.51). LIMITATIONS: The sample size of the study was relatively modest, limiting the number of variables included in the analysis. CONCLUSIONS: Results confirm that psychomotor change, anhedonia and negative affect are key MDD dimensions, two of which are related to treatment outcome. PMID- 24210630 TI - Cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression. AB - BACKGROUND: The uncertainty over the true morphological changes in brains with major depressive disorder (MDD) underlines the necessity of comprehensive studies with multimodal structural brain imaging analyses. This study aimed to evaluate the differences in cortical thickness, cortical and subcortical volume, and white matter integrity between first episode, medication-naive MDD patients and healthy controls. METHODS: Subjects with their first episode of MDD whose illness duration had not exceeded 6 months (n=20) were enrolled in this study and were compared to age-, sex-, and education level-matched healthy controls (n=22). All participants were subjected to T1-weighted structural magnetic resonance imaging (MRI). We used an automated procedure of FreeSurfer and Tract-based spatial statistics (TBSS) to analyze differences in cortical thickness, cortical and subcortical volume, and white matter integrity between two groups. RESULTS: The patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (P<0.0015) compared to healthy controls. We also observed altered white matter integrity in the body of the corpus callosum (P<0.01), reduced cortical volume of the caudal middle frontal gyrus and medial orbitofrontal gyrus, and enlarged hippocampal volume in the first episode MDD patients. LIMITATIONS: We relied on a relatively small sample size and cortical volume reduction in several brain regions was not replicated in the analysis of cortical thickness. CONCLUSIONS: Using multimodal imaging analyses on medication-naive first episode MDD patients, we demonstrated fundamental structural alteration of brain gray and white matter, such as reduced cortical volume of the caudal ACC and white matter integrity in the body of the corpus callosum. PMID- 24210631 TI - Radiolabeled nanoceria probes may reduce oxidative damages and risk of cancer: a hypothesis for radioisotope-based imaging procedures. AB - Low-dose ionizing radiations are commonly utilized in medical centers for diagnostic imaging procedures. Unfortunately, the absorption of ionizing radiation generates reactive chemical species that could damage cells. In diagnostic radioisotope-based imaging procedures, the radiological exposures by gamma emitter imaging probes such as radioactive technetium ((99m)Tc) could express low risk of cancer. Recently, many studies have documented cell protective, neuro-protective, anti-inflammatory and cardio-protective properties of cerium oxide nanoparticles (nanoceria) as a result of their antioxidant and free radical scavenger properties. Since there is no safe level of ionizing radiations, then we hypothesize that radiolabeled nanoceria might be an interesting probe to reduce cancer risk and other related oxidative stresses. We also provide a synthetic scheme of nanoceria functionalization with fluorine radiolabeled ligands as an exemplary approach. In conclusion, using nanoceria to combine radioisotope-based imaging probes with antioxidant activity might open new way to protect patient against radioactive emission of radioisotopes and ionizing radiations in several radioisotope-based imaging applications, in particular for patients who need frequent imaging procedures and children who are more susceptible to radiation. PMID- 24210632 TI - FOLICation: engineering approved drugs as potential p53-MDM2 interaction inhibitors for cancer therapy. AB - Cancer is characterized by uncontrolled growth of abnormal cells leading to the formation of tumors. Normally, the pro-apoptotic p53 protein plays a central role in protecting cells against carcinogenesis. In almost 50% human tumor cells, however, the p53 protein is dysregulated by direct interaction with its negative regulator, the Murine Double Minute 2 (MDM2) protein. Therefore, blocking the p53 binding pocket on MDM2, leading to the activation of tumor suppressor p53 presents a novel therapeutic strategy against several types of cancers. The published crystal structure of MDM2 bound with the p53 binding domain has revealed that three key hydrophobic residues of p53 are buried deep into the binding cavity of MDM2 and thus are central to p53-MDM2 binding. Accordingly, several low-molecular-weight compounds have been developed that mimic these three hydrophobic residues and thus bind to the MDM2 pocket, leading in turn to inhibition of the deleterious p53-MDM2 interaction. It is noteworthy that these inhibitors also possess an additional hydrophilic group that is shown to be necessary as a "cover" protecting the hydrophobic interaction surface between inhibitor and MDM2 from surrounding solvent. In comparison, several FDA-approved drugs possess the three key hydrophobic features necessary for binding to MDM2, but lack the fourth hydrophilic moiety, thus possibly hindering their ability as potential p53-MDM2 interaction inhibitors. Therefore, we hypothesize that conjugation of hydrophilic vitamin folic acid or its analogs to these drugs (termed "FOLICation") may provide them with the much-needed hydrophilic cover and make them suitable for investigation as potentially novel p53-MDM2 inhibitors. We also anticipate that FOLICation of these drugs may further lead to their enhanced and selective uptake by cancer cells, owing to the significantly higher expression of folic acid receptors on cancer cells compared to normal cells. PMID- 24210633 TI - Calcium risk-benefit updated--new WHI analyses. PMID- 24210634 TI - Scientific principles of regenerative medicine and their application in the female reproductive system. AB - The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system. PMID- 24210635 TI - Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. AB - OBJECTIVES: Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals. STUDY DESIGN: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data. MAIN OUTCOME MEASURES: Incidence of CVD. RESULTS: After a mean follow-up of 5.6+/-1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD. CONCLUSIONS: Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events. PMID- 24210636 TI - Longevity and diet. Myth or pragmatism? AB - Longevity is a very complex phenomenon, because many environmental, behavioral, socio-demographic and dietary factors influence the physiological pathways of aging and life-expectancy. Nutrition has been recognized to have an important impact on overall mortality and morbidity; and its role in extending life expectancy has been the object of extensive scientific research. This paper reviews the pathophysiological mechanisms that potentially link aging with diet and the scientific evidence supporting the anti-aging effect of the traditional Mediterranean diet, as well as of some specific foods. The diet and several of its components have additionally been shown to have beneficial effects on the co morbidities typical of elderly populations. Furthermore, the epigenetic effects of diet on the aging process - through calorie restriction and the consumption of foods like red wine, orange juice, probiotics and prebiotics - have attracted scientific interest. Some, such as dark chocolate, red wine, nuts, beans, avocados are being promoted as anti-aging foods, due to their anti-oxidative and anti-inflammatory properties. Finally, an important moderator in the relationship between diet, longevity and human health remains the socio-economic status of individual, as a healthy diet, due to its higher cost, is closely related to higher financial and educational status. PMID- 24210637 TI - [Results after internal fixation of humerus distal fractures in patients over than 65 years old]. AB - INTRODUCTION AND OBJECTIVE: Distal humerus fractures in the elderly frequently associated with poor bone quality and comminution, making it harder to achieve proper osteosynthesis. Our aim is to evaluate the radiological and functional results of open reduction and internal fixation of these fractures. MATERIAL AND METHODS: Retrospective study of 26 patients treated by open reduction and internal fixation between the years 2005-2010. Mean follow-up was 42 months. At final follow-up, a radiography evaluation (Knirk and Jupiter score) and clinical examination using Mayo Elbow Performance Score and Quick-Disabilities of the Arm, Shoulder and Hand Score was performed. Mean age of the group was 76.8 years (65 89), with 83% of the patients being female. Sixteen patients suffered type C fractures and 8 type A by AO classification. All underwent posterior surgical approach. RESULTS: Mean elbow flexion reached 118.86 degrees , with a mean extension deficit of 25 degrees . More than 3-quarters (79.1%) of the patients showed 0-1 grade degenerative changes on the X-ray films at final follow-up. Functional results reached an average 19.87 points on Quick-Disabilities of the Arm, Shoulder and Hand Score, and 85 points on Mayo Elbow Performance Score scores. Non-union occurred in 2 cases: distal humerus in one patient and olecranon osteotomy in another. Ulnar nerve neuropraxia was recorded in 2 cases, and radial nerve in one. All 3 recovered uneventfully. Revision surgery was required, with 2 patients needing hardware removal and one a new fixation. DISCUSSION: Treatment by open reduction and internal fixation with plating in elderly people for type A and C distal humerus fractures gives good functional results regarding this population, and thus scarcely disturbs their quality of life. PMID- 24210638 TI - Stability of transforaminal lumbar interbody fusion in the setting of retained facets and posterior fixation using transfacet or standard pedicle screws. AB - BACKGROUND CONTEXT: The transforaminal lumbar interbody fusion (TLIF) technique supplements posterior instrumented lumbar spine fusion and has been tested with different types of screw fixation for stabilization. Transforaminal lumbar interbody fusion is usually placed through a unilateral foraminal approach after unilateral facetectomy, although extraforaminal entry allows the facet to be spared. PURPOSE: To characterize the biomechanics of L4-L5 lumbar motion segments instrumented with bilateral transfacet pedicle screw (TFPS) fixation versus bilateral pedicle screw-rod (PSR) fixation in the setting of intact facets and native disc or after discectomy and extraforaminal placement of a TLIF technology graft. STUDY DESIGN: Human cadaveric lumbar spine segments were biomechanically tested in vitro to provide a nonpaired comparison of four configurations of posterior and interbody instrumentation. METHODS: Fourteen human cadaveric spine specimens (T12-S1) underwent standard pure moment flexibility tests with intact L4-L5 disc and facets. Seven were studied with intact discs, after TFPS fixation, and then with TLIF and TFPS fixation. The others were studied with intact discs, after PSR fixation, and then combined with extraforaminally placed TLIF. Loads were applied about anatomic axes to induce flexion-extension, lateral bending, and axial rotation. Three-dimensional specimen motion in response to applied loads during flexibility tests was determined. A nonpaired comparison of the four configurations of posterior and interbody instrumentation was made. RESULTS: Transfacet pedicle screw and PSR, with or without TLIF, significantly reduced range of motion during all directions of loading. Transfacet pedicle screw provided greater stability than PSR in all directions of motion except lateral bending. In flexion, TFPS was more stable than PSR (p=.042). A TLIF device provided less stability than the intact disc in constructs with TFPS and PSR. CONCLUSIONS: These results suggest that fixation at L4-L5 with TFPS is a promising alternative to PSR, with or without TLIF. A TLIF device was less stable than the native disc with both methods of instrumentation presumably because of a fulcrum effect from a relatively small footplate. Additional interbody support may be considered for improved biomechanics with TLIF. PMID- 24210639 TI - Genome-wide association studies of lumbar disc degeneration--are we there yet? PMID- 24210640 TI - New intervertebral device? No, just a bullet inside the L3-L4 disc. PMID- 24210641 TI - [Interest of emergency dermatological consultation in a regional hospital]. AB - INTRODUCTION: Dermatologists, both as hospital and as resident practitioners, are often requested to see emergencies of their discipline, although appointment planning are already fully booked months in advance. Orleans Regional Hospital (ORH) has opened a department of dermatological emergency consultation to try to help with this issue. A prospective, descriptive and consecutive study on patient characteristics was conducted during its first year operating. METHOD: In September 2011, we opened a department of dermatological emergency consultation. Reception is skin disorders evaluated by physicians or nurses as "emergencies", according to predefined criteria. Follow-up visits are performed in the afternoon. RESULTS: Within one year, 2209 medical visits were conducted, with an average of 8,7 emergency visits per day. The maximum numbers of patients treated by our dermatological emergency unit in one single morning was 19. Mondays were the busiest day of the week. The average age of a patient attending the department was 33 years, with 29% of pediatric patients (under 15 years old). The majority of patients presented spontaneously (43%), or were referred by general practitioners (25%). Adult and pediatric emergency departments sent 8% of patients. The two main reasons for consultation were rash (48%) and pruritus (16%). Diagnoses observed were mainly infections (24%) and eczema (14%). Scabies accounted for 9% of all diagnoses. In the aftermath of an emergency dermatological consultation, 84 patients were hospitalized, including 74 in the dermatology department of Orleans hospital totalling 505 days of hospitalization. CONCLUSION: The value of a dermatological emergency consultation is well demonstrated in areas where more medical services are available (such as cities with University hospitals available). It is even more justified in areas with a deficit of healthcare service availability such as Central France. PMID- 24210642 TI - [Still a place for hormone replacement therapy?]. AB - Hormone replacement therapy (HRT) remains the most efficient treatment to alleviate climacteric symptoms. The drastic decline in their prescription following the WHI is not fully justified. Benefits might be more important than harm in women 50-60 years. French way of treatment does not increase the risk in thrombosis nor stroke and breast cancer risk is less important than with other regimen. One of the major benefits of HRT is the decrease in type 2 diabetes with all the treatments including the French ones. The results of the American randomized trials cannot be fully extrapolated to young postmenopausal women with less cardiovascular risk factors. PMID- 24210643 TI - CpG oligonucleotides protect against Venezuelan equine encephalitis virus infection in a route-dependent manner. PMID- 24210644 TI - The intra- and inter-rater reliability of component analysis of rise from supine in the children with typical development and developmental delay. AB - The purpose of this study was to determine the intra- and inter-rater reliability of classifying the movement patterns of rising from supine to stand in the children with typical development (TD) and mild to moderate developmental delay (DD). Sixty-eight children with TD and 20 children with DD aged 2 through 6 years were videotaped during rising. Two trained pediatric physical therapists independently viewed each videotape and classified the movement patterns of upper extremities (UE), trunk/axial (AX) and lower extremities (LE) regions using descriptive categories developed by previous researchers. Kappa statistic and average percentage of agreement were calculated to determine reliability. The average agreement rate of intra-rater ranged from 90% to 97% in TD group for three regions, and 79% to 89% in DD group; the agreement rate between raters ranged from 82% to 95% in TD group for three regions, and 71% to 87% in DD group. Using kappa statistic guidelines, high intra- and inter-rater reliabilities (k>0.81) were found in TD group, except inter-rater reliability for LE. Substantial intra- and inter-reliabilities (0.61beta-beta'>beta-O-4'. The MSR were mainly from the decomposition and re polymerization of lignin. This study suggests that characterization of MSR provides a promising method to investigate the mechanisms of cypress liquefaction in ethanol. PMID- 24210650 TI - Impact of an external electron acceptor on phosphorus mobility between water and sediments. AB - The present work assessed the impact of an external electron acceptor on phosphorus fluxes between water and sediment interface. Microcosm experiments simulating a sediment microbial fuel cell (SMFC) were carried out and phosphorus was extracted by an optimized combination of three methods. Despite the low voltage recorded, ~96 mV (SMFC with carbon paper anode) and ~146 mV (SMFC with stainless steel scourer anode), corresponding to a power density of 1.15 and 0.13 mW/m(2), it was enough to produce an increase in the amounts of metal bound phosphorus (14% vs 11%), Ca-bound phosphorus (26% vs 23%), and refractory phosphorus (33% vs 28%). These results indicate an important role of electroactive bacteria in the phosphorus cycling and open a new perspective for preventing metal bound phosphorus dissolution from sediments. PMID- 24210651 TI - Calcitriol decreases TGF-beta1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats. AB - Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-beta1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of alpha-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-beta1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-beta1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of alpha-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-beta1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-beta1 and angiotensin II production. PMID- 24210652 TI - Response to Baker, J., Mitchell, R., Pell, J., Cross-sectional study of ethnic differences in the utility of area deprivation measures to target socioeconomically deprived individuals, Social Science & Medicine 85 (2013) 27 31. PMID- 24210653 TI - Cap-assisted gastroscope versus cap-assisted colonoscope for examination of difficult sigmoid colons in a nonsedated Asian population: a randomized study. AB - BACKGROUND: Studies have estimated that cecal intubation failure occurs with conventional colonoscopy in about 10% of cases. Various methods have been adopted to improve the cecal intubation rate, including a transparent cap and special colonoscopes. OBJECTIVE: To assess the efficacy of using a cap-assisted gastroscope (E-cap) compared with a cap-assisted colonoscope (C-cap) for the complete examination of the colon in nonsedated patients with technically difficult sigmoid colons. DESIGN: Randomized, controlled study. SETTING: Tertiary care referral center. PATIENTS: One hundred thirty-nine patients with technically difficult sigmoid colons were studied. INTERVENTION: Colonoscopy with either an E cap (n = 69) or a C-cap (n = 70). MAIN OUTCOME MEASUREMENTS: Cecal intubation rate, cecal intubation time, patient-assessed pain score, and endoscopist assessed pain score. RESULTS: The cecal intubation rate was significantly higher in the E-cap (65/69, 94.2%) than in the C-cap group (50/70, 71.4%; P < .0001). Patient-assessed pain (moderate to severe) was more frequently reported in the C cap (14/70, 20.0%) than in the E-cap group (5/69, 7.2%; P = .029). Endoscopist assessed pain (moderate to severe) was more frequently reported in the C-cap (13/70, 18.6%) than in the E-cap group (3/69, 7.2%; P = .009). For patients with a low body mass index (<= 22 kg/m(2)), the cecal intubation rate was significantly higher in the E-cap (37/38, 97.4%) than in the C-cap group (15/29, 51.7%; P < .0001). LIMITATIONS: Single-center experience, lack of a gastroscope control group without a cap. CONCLUSION: The cap-assisted gastroscope is more tolerable and effective than cap-assisted colonoscope for the complete examination of the colon in patients with technically difficult sigmoid colons. ( CLINICAL TRIAL REGISTRATION NUMBER: KCT0000744.). PMID- 24210654 TI - Predictors of incomplete resection and perforation associated with endoscopic submucosal dissection for colorectal tumors. AB - BACKGROUND AND OBJECTIVE: Colorectal endoscopic submucosal dissection (ESD) is technically challenging. Our aim was to identify predictors of incomplete resection and perforation in colorectal ESD. DESIGN: Retrospective study. SETTING: Academic Japanese endoscopy unit. PATIENTS AND MAIN OUTCOME MEASUREMENTS: A total of 267 consecutive cases of colorectal tumors treated by ESD from May 2010 to February 2013 were analyzed. Predictors of incomplete resection and perforation, including lesion size, growth type, pathological diagnosis, use of hemostatic forceps, degree of fibrosis, history of biopsy, history of local endoscopic treatment, and endoscopic operability. RESULTS: The incomplete resection rate was 4.1%. The perforation rate was 5.6%. Univariate analysis identified severe fibrosis (P = .032), submucosal (SM) deep (>1000 MUm) invasion (P = .033) and poor endoscopic operability (P = .030) as predictors of incomplete resection, and severe fibrosis (P = .038), postendoscopic treatment (P = .016), and poor endoscopic operability (P = .012) as predictors of perforation. Multivariate analysis identified poor endoscopic operability and SM deep invasion as independent predictors of incomplete resection, and poor endoscopic operability and severe fibrosis as independent predictors of perforation. There was no adjustment of P values for multiple testing. LIMITATION: A single-center study by a single colonoscopist. All statistical results should be taken as descriptive only. CONCLUSIONS: Poor endoscopic operability and SM deep invasion were significant independent predictors of incomplete resections. Poor endoscopic operability and severe fibrosis were significant independent predictors of perforation. These features may provide helpful information when planning colorectal ESD. PMID- 24210655 TI - The Welsh Institute for Minimal Access Therapy colonoscopy suitcase has construct and concurrent validity for colonoscopic polypectomy skills training: a prospective, cross-sectional study. AB - BACKGROUND: The Welsh Institute for Minimal Access Therapy (WIMAT) colonoscopy suitcase is an ex vivo porcine simulator for polypectomy training. OBJECTIVE: To establish whether this model has construct and concurrent validity. DESIGN: Prospective, cross-sectional study. SETTING: Endoscopic training center. PARTICIPANTS: Twenty novice (N), 20 intermediate (I), 20 advanced (Ad), and 20 expert (E) colonoscopists. INTERVENTION: A simulated polypectomy task aimed at removing 2 polyps; A (simple), B (complex). MAIN OUTCOME MEASUREMENTS: Two accredited colonoscopists, blinded to group allocation, scored performances according to Direct Observation of Polypectomy Skills (DOPyS) assessment parameters. Group performances were compared. Real-life DOPyS scores were correlated to simulator DOPyS results. RESULTS: Median overall DOPyS scores for novices were 1.00 (1.00-1.87) for A and 0.50 (0.00-1.00) for B (A vs B; P < .01). Intermediates scored 2.50 (2.00-2.88) for A and 2.00 (1.13-2.50) for B (A vs B; P = .03). The advanced group scored 3.00 (2.50-3.50) for A and 2.50 (2.00-3.00) for B (A vs B; P = .01). Experts scored 3.00 (3.00-3.88) for A and 3.00 (2.50-3.50) for B (A vs B; P = .47). Intergroup comparisons for A were, N vs I; P < .01, N vs Ad; P < .01, N vs E; P < .01, I vs Ad; P < .01, I vs E; P < .01, and Ad vs E; P = .46. Intergroup comparisons for B were, N vs I; P < .01, N vs Ad; P < .01, N vs E; P < .01, I vs Ad; P = .03, I vs E; P <.01, and Ad vs E; P = .06. There was no difference between real-life DOPyS scores and simulator scores (0.07). LIMITATIONS: The model does not have inbuilt assessment parameters. CONCLUSION: This simulator demonstrates construct and concurrent validity for colon polypectomy training. PMID- 24210656 TI - The production process of "Etude sur le Rein des Urinaires", doctoral thesis of Joaquin Maria Albarran at the Faculty of Medicine in Paris. AB - OBJECTIVES: The manuscript of the Doctoral Thesis of Joaquin Albarran in the Faculty of Medicine in Paris "Etudesur le Rein des Urinaires" has been donated to Asociacion Espanola de Urologia. Direct comparison of the original and printed material gives information of the production process of this master work. MATERIAL AND METHODS: Direct comparison between the original hand-written work, a single hard bound volume covered with loin cloth and water paper composed of 145 numbered pages plus 206 newly numbered pages of clinico-pathological (37 subjects) and experimental (19 assays in 20 rabbits) data, and the printed work edited by Georges Steinheil in 1889. Prints included 4 plates with 14 figures, 9 temperature charts and 5 tables describing urine examinations. Figures were trichromic and charts and tables black & white. Chromolithographs were produced by Mr. Leuba in the printing owned by Lemercier et Cie, Paris. RESULTS: The original work was completed in 1887 without any correction or deletion. Differences are noticeable between the text in the master and printed works: rearrangement of data and inclusion of a new clinical observation, 5 new experiments, summary and dedications. Changes in iconography are noticeable. The masterwork included 24 plates (numbered from 1 to 22, 13bis, 16bis) with 46 figures (44 colored) integrated within the text and 26 double-page temperature registries that accompany clinical observations. Anatomical, histological and microbiological illustrations, including culture media, microbiological stains and histobacteriological preparations were depicted as watercolors (44%), watercolors mixed with pencil or ink (52%) or pencil drawings (4%). Four (9%) were signed by the author, 5 (11%) had numerical annotations and only 14 (30%) were definitely printed with loss of the black component and redrawn of 4/14 (29%) images. The largest images were not printed. CONCLUSIONS: Joaquin Albarran described and beautifully illustrated himself the role "pyogenic bacillus" (E. coli) played in renal infection, bacteriemia, renal failure sepsis and patient death. The evolution of pyelonephritis to perinephritis and perinephric abscess was masterly interpreted, with new description of ascending infection and lymphatic peritubular dissemination of bacteria. The differences detected between written and printed work are numerous and can be explained by the corrections of Prof. Guyon before definite presentation and the technical process to perform the lithographs. PMID- 24210657 TI - First discovery of Pleistocene orangutan (Pongo sp.) fossils in Peninsular Malaysia: biogeographic and paleoenvironmental implications. AB - Nine isolated fossil Pongo teeth from two cave sites in Peninsular Malaysia are reported. These are the first fossil Pongo specimens recorded in Peninsular Malaysia and represent significant southward extensions of the ancient Southeast Asian continental range of fossil Pongo during two key periods of the Quaternary. These new records from Peninsular Malaysia show that ancestral Pongo successfully passed the major biogeographical divide between mainland continental Southeast Asia and the Sunda subregion before 500 ka (thousand years ago). If the presence of Pongo remains in fossil assemblages indicates prevailing forest habitat, then the persistence of Pongo at Batu Caves until 60 ka implies that during the Last Glacial Phase sufficient forest cover persisted in the west coast plain of what is now Peninsular Malaysia at least ten millennia after a presumed corridor of desiccation had extended to central and east Java. Ultimately, environmental conditions of the peninsula during the Last Glacial Maximum evidently became inhospitable for Pongo, causing local extinction. Following post-glacial climatic amelioration and reforestation, a renewed sea barrier prevented re-colonization from the rainforest refugium in Sumatra, accounting for the present day absence of Pongo in apparently hospitable lowland evergreen rainforest of Peninsular Malaysia. The new teeth provide further evidence that Pongo did not undergo a consistent trend toward dental size reduction over time. PMID- 24210658 TI - Continuous dental eruption identifies Sts 5 as the developmentally oldest fossil hominin and informs the taxonomy of Australopithecus africanus. AB - The relatively small Australopithecus africanus specimen Sts 5 has figured prominently in taxonomic debates, and the determination of this specimen as a young male or an elderly female has the potential to offer a great deal of resolution on this question. Sts 5 has been argued to be either a small, immature male or a mature female based on a variety of characters. A proposed model of continuous root remodeling and angular change for heavily worn dentition may account for the extremely short tooth roots, particularly for the anterior dentition, that Sts 5 demonstrates. The anterior tooth roots of Sts 5 are oriented vertically (relative to the alveolar plane), unlike those found in most other apes, humans, and fossil specimens, in which the tooth roots are roughly parallel with the plane of the nasoalveolar clivus. Computed tomography (CT) data of adult apes were examined and a relationship between the angle of the anterior tooth roots and their length was discovered, caused by heavily worn anterior dentition continuing to erupt to maintain occlusion. The extremely short and vertically oriented anterior roots observed in Sts 5 thus suggest that the specimen represents an aged female specimen with extremely worn dentition. Interestingly, this reorientation of anterior tooth roots helps account for the unusual nasoalveolar contour of Sts 5. The remodeling associated with the heavily worn teeth and reoriented roots thus resolves the taxonomic question raised by analyses identifying unusual prognathism of this small specimen. PMID- 24210659 TI - [Brain metastases from breast cancer]. AB - Breast cancer is the second leading cause of brain metastases and account for 15 % of metastatic breast cancer patients. Several patient- and tumor-related characteristics have been identified as risk factors for developing brain metastases. Treatment is based on local and/or systemic therapies, tailored to breast cancer brain metastases-specific prognostic factors. This article is an update on the current knowledge of the incidence, prognosis and prognostic factors, treatment and perspectives in brain metastases from breast cancer. PMID- 24210660 TI - Self-assembly of VPS41 promotes sorting required for biogenesis of the regulated secretory pathway. AB - The regulated release of polypeptides has a central role in physiology, behavior, and development, but the mechanisms responsible for production of the large dense core vesicles (LDCVs) capable of regulated release have remained poorly understood. Recent work has implicated cytosolic adaptor protein AP-3 in the recruitment of LDCV membrane proteins that confer regulated release. However, AP 3 in mammals has been considered to function in the endolysosomal pathway and in the biosynthetic pathway only in yeast. We now find that the mammalian homolog of yeast VPS41, a member of the homotypic fusion and vacuole protein sorting (HOPS) complex that delivers biosynthetic cargo to the endocytic pathway in yeast, promotes LDCV formation through a common mechanism with AP-3, indicating a conserved role for these proteins in the biosynthetic pathway. VPS41 also self assembles into a lattice, suggesting that it acts as a coat protein for AP-3 in formation of the regulated secretory pathway. PMID- 24210662 TI - Inverse association between 18-carbon trans fatty acids and intelligence quotients in smoking schizophrenia patients. AB - This study aimed to investigate polyunsaturated (PUFA) and trans isomeric fatty acid status in schizophrenia patients. Fatty acid composition of plasma phospholipids (PL) and triacylglycerols (TG) was analyzed by gas chromatography in 29 schizophrenia patients and 15 healthy controls. We found no difference in PL n-3 fatty acid status between the two groups, while the values of 22:5n-6 were significantly higher in patients with schizophrenia than in controls. In TG, values of docosatrienoic acid (20:3n-3) and docosapentaenoic acid (20:5n-3) were significantly higher in schizophrenia patients than in controls. We found no difference in the trans fatty acid status between patients and controls. In smoking schizophrenia patients significant negative correlations were detected between Wechsler adult full-scale intelligence quotients and values of total trans fatty acids in PL lipids, whereas no such correlation was seen either in non-smoking schizophrenia patients, or in healthy controls. While data obtained in the present study fail to furnish evidence for n-3 PUFA supplementation to the diet of patients with schizophrenia, they indicate that in smoking schizophrenia patients high dietary exposure to trans fatty acids is associated with lower intelligence quotients. PMID- 24210661 TI - Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors. AB - Morphogenesis requires the proper migration and positioning of different cell types in the embryo. Much more is known about how cells start and guide their migrations than about how they stop when they reach their destinations. Here we provide evidence that Rbx2, a subunit of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, stops neocortical projection neurons at their target layers. Rbx2 mutation causes neocortical and cerebellar ectopias dependent on Dab1, a key signaling protein in the Reelin pathway. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7 is upregulated during projection neuron migration, and unscheduled SOCS7 expression stops migration prematurely. Cerebellar development requires Rbx2 but not SOCS7, pointing to the importance of other CRL5 adaptors. Our results suggest that CRL5 adaptor expression is spatiotemporally regulated to modulate Reelin signaling and ensure normal neuron positioning in the developing brain. PMID- 24210663 TI - Clonidine in Tourette syndrome and sensorimotor gating. PMID- 24210664 TI - Evaluative beliefs as mediators of the relationship between parental bonding and symptoms of paranoia and depression. AB - This study was aimed to explore the distinct pathways that lead to depression and paranoia. We first examined the association of dysfunctional parenting experiences and negative self-evaluations in depression and paranoia. Furthermore, we also examined whether different self-evaluative beliefs could mediate the relationships between dysfunctional parenting experiences (i.e. parental overprotection or lack of care) and the development of depression and paranoia. A sample composed of 55 paranoid patients, 38 depressed patients and 44 healthy controls completed the Parental Bonding Instrument (PBI), the Evaluative Beliefs Scale (EBS) and some clinical scales. Our analyses revealed that lack of parental care and negative self-self evaluations were associated with depression symptoms. Analyses also revealed that parental overprotection and negative other self evaluations were associated with paranoid symptoms. Furthermore, negative self-self and other-self evaluations fully mediated the relationship of parental overprotection and paranoia, whereas negative self-self evaluations partially mediated the relationship between lack of parental care and depression. These findings suggest that distinct patterns of parental practices may contribute to the development of different dysfunctional schemas which in turn may lead to either depression or paranoia. PMID- 24210665 TI - Absence of low frequency variants associated with schizophrenia at the ultraconserved non-coding region of TCF4. PMID- 24210666 TI - EQ-5D as a measure of programme outcome: results from the Singapore early psychosis intervention programme. AB - The current study aimed to establish the Health-Related Quality of Life (HRQoL) among participants with First Episode Psychosis (FEP) in Singapore, to elucidate the sociodemographic and clinical correlates of HRQoL, and ascertain the change after 1-year of treatment. Two hundred and forty one patients accepted into an Early Psychosis Intervention Programme (EPIP) from April 2009 to June 2011 and who had completed baseline EuroQol-5D (EQ-5D) assessments were included in this analysis. The mean (S.D.) EQ-5D index at baseline was 0.788 (0.258). One hundred thirty five (56.0%) patients who completed the EQ-5D assessment at the 12-month follow-up had a significantly higher EQ-5D index as compared to baseline. EQ-5D index was significantly higher among those patients who met criteria for remission at the 12-month interval than those who were not in remission. Our results suggest that the EQ-5D is responsive to improvement as it corresponded well to objective ratings of remission in our patients with FEP. PMID- 24210667 TI - Clinical specificity of acute versus chronic self-injury: measurement and evaluation of repetitive non-suicidal self-injury. AB - Overall, previous studies on the prevalence of non-suicidal self-injury (NSSI) behaviors in the general population have stressed the importance of differentiating between occasional and repetitive NSSI, examining different severity levels (e.g., frequency and variety of methods), as well as investigating the diverse psychopathological correlates of NSSI. However, existing NSSI measures have not been explicitly developed by to comply with the NSSI diagnostic criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The purpose of this study is to develop a measure of repetitive NSSI by considering its essential features, as described in the proposed DSM-5 as well as in other clinically relevant aspects emerging from case reports. Two independent samples of participants (N1=383 young adults and 251 adolescents; N2=953 adolescents) belonging to the general population were involved in the present study. The questionnaire showed satisfactory fit statistics and reliably discriminated between occasional and repetitive self injurers (Area Under Curve, AUC=0.755). The pattern of correlations with psychopathological measures confirmed a more clinically-compromised profile for repetitive rather than occasional self-injurers. PMID- 24210668 TI - Intraoperative validation of navigated limb measurements in THA using a pinless femoral array. AB - Appropriate limb length (LL) and femoral offset (OS) after total hip arthroplasty (THA) are crucial for a successful and lasting outcome. However, intraoperative assessment is difficult. Computed navigation is effective but the use of radiation and of invasive bone references is cause of concern. Imageless, pinless navigation systems have been shown to be accurate in experimental studies. However, almost no clinical validation has been performed. We used a minimally invasive computer-navigated system (MICNS) in conjunction with an imageless measurement technique for implanting 60 consecutive THAs. Head/neck trial components of different size were applied, and the differences in LL and femoral OS measurements were recorded and compared to the implant manufacturer's specifications, corrected for the anatomical variations of each patient. The imageless MICNS revealed a valid and accurate intra-operative tool for measuring LL and femoral OS in vivo. PMID- 24210669 TI - Expression of PLIN2 and PLIN3 during oocyte maturation and early embryo development in cattle. AB - In vitro-produced embryos store high lipid content in cytoplasmic lipid droplets (LD), and reduction or removal of LD has been demonstrated to improve freeze-thaw viability. The Perilipin Adipophilin Tail-interacting Protein of 47 kD (PAT) family of proteins is involved in the formation and regulation of LD in many cell types, but their presence has not been addressed either in cattle oocytes or preimplantation embryos. Therefore, this study aimed to detect the expression of PAT family transcripts (Perilipin-2 [PLIN2] and Perilipin-3 [PLIN3]) in immature and in vitro-matured (IVM) oocytes, and in in vitro-produced embryos at the stages of two to four cells, eight to 16 cells, morulae (MO), and blastocyst (BL). The expression of PLIN3 was downregulated in response to IVM, and PLIN2 was comparatively more expressed than PLIN3 in IVM oocytes (P < 0.001). During the early stages of embryo development, PLIN2 expression reached its peak at the MO stage (P < 0.001) and decreased again at the BL stage. In contrast, PLIN3 was expressed in low levels during the earliest stages of development, slightly upregulated at the MO stage (P < 0.05), and greatly increased its expression at the BL stage (15-fold; P < 0.001). PLIN3 was comparatively more expressed than PLIN2 during embryo culture in most stages analyzed (P < 0.05), except in eight- to 16-cell embryos. These results indicate that PLIN2 might be involved in the maintenance of lipid stocks necessary to support embryo development after fertilization of IVM oocytes. Also, we hypothesize that PLIN3 is the main PAT protein responsible for stabilization of LD formed in consequence of the acute lipid load seen during embryo development. We confirmed the presence of both PLIN2 and PLIN3 proteins in BL at Day 7 using immunocytochemistry: these PAT proteins colocalized with LD stained with BODIPY. PLIN3 seemed to be more ubiquitously spread out in the cytoplasm than PLIN2, consistent with the pattern seen in adipocytes. These findings suggest that both elderly (bigger) and newly formed (smaller) LD, positive for PLIN2 and PLIN3 respectively, coexist in blastocysts. To our knowledge this is the first report showing that transcripts of the PAT family are present in cattle oocytes and embryos. PMID- 24210670 TI - Standing on the shoulders of giants: results from the Radiation Oncology Academic Development and Mentorship Assessment Project (ROADMAP). AB - PURPOSE: To analyze survey information regarding mentorship practices and cross correlate the results with objective metrics of academic productivity among academic radiation oncologists at US Accreditation Council for Graduate Medical Education (ACGME)-accredited residency training programs. METHODS AND MATERIALS: An institutional review board-approved survey for the Radiation Oncology Academic Development and Mentorship Assessment Project (ROADMAP) was sent to 1031 radiation oncologists employed at an ACGME-accredited residency training program and administered using an international secure web application designed exclusively to support data capture for research studies. Data collected included demographics, presence of mentorship, and the nature of specific mentoring activities. Productivity metrics, including number of publications, number of citations, h-index, and date of first publication, were collected for each survey respondent from a commercially available online database, and m-index was calculated. RESULTS: A total of 158 academic radiation oncologists completed the survey, 96 of whom reported having an academic/scientific mentor. Faculty with a mentor had higher numbers of publications, citations, and h- and m-indices. Differences in gender and race/ethnicity were not associated with significant differences in mentorship rates, but those with a mentor were more likely to have a PhD degree and were more likely to have more time protected for research. Bivariate fit regression modeling showed a positive correlation between a mentor's h-index and their mentee's h-index (R2=0.16; P<.001). Linear regression also showed significant correlates of higher h-index, in addition to having a mentor (P=.001), included a longer career duration (P<.001) and fewer patients in treatment (P=.02). CONCLUSIONS: Mentorship is widely believed to be important to career development and academic productivity. These results emphasize the importance of identifying and striving to overcome potential barriers to effective mentorship. PMID- 24210671 TI - Initial clinical experience performing patient treatment verification with an electronic portal imaging device transit dosimeter. AB - PURPOSE: To prospectively evaluate a 2-dimensional transit dosimetry algorithm's performance on a patient population and to analyze the issues that would arise in a widespread clinical adoption of transit electronic portal imaging device (EPID) dosimetry. METHODS AND MATERIALS: Eleven patients were enrolled on the protocol; 9 completed and were analyzed. Pretreatment intensity modulated radiation therapy (IMRT) patient-specific quality assurance was performed using a stringent local 3%, 3-mm gamma criterion to verify that the planned fluence had been appropriately transferred to and delivered by the linear accelerator. Transit dosimetric EPID images were then acquired during treatment and compared offline with predicted transit images using a global 5%, 3-mm gamma criterion. RESULTS: There were 288 transit images analyzed. The overall gamma pass rate was 89.1%+/ 9.8% (average+/-1 SD). For the subset of images for which the linear accelerator couch did not interfere with the measurement, the gamma pass rate was 95.7%+/ 2.4%. A case study is presented in which the transit dosimetry algorithm was able to identify that a lung patient's bilateral pleural effusion had resolved in the time between the planning CT scan and the treatment. CONCLUSIONS: The EPID transit dosimetry algorithm under consideration, previously described and verified in a phantom study, is feasible for use in treatment delivery verification for real patients. Two-dimensional EPID transit dosimetry can play an important role in indicating when a treatment delivery is inconsistent with the original plan. PMID- 24210672 TI - What roles do team climate, roster control, and work life conflict play in shiftworkers' fatigue longitudinally? AB - The study aimed to examine shiftworkers fatigue and the longitudinal relationships that impact on fatigue such as team climate, work life conflict, control of shifts and shift type in shift working nurses. We used a quantitative survey methodology and analysed data with a moderated hierarchical multiple regression. After matching across two time periods 18 months apart, the sample consisted of 166 nurses from one Australian hospital. Of these nurses, 61 worked two rotating day shifts (morning & afternoon/evening) and 105 were rotating shiftworkers who worked three shifts (morning afternoon/evening and nights). The findings suggest that control over shift scheduling can have significant effects on fatigue for both two-shift and three-shift workers. A significant negative relationship between positive team climate and fatigue was moderated by shift type. At both Time 1 and Time 2, work life conflict was the strongest predictor of concurrent fatigue, but over time it was not. PMID- 24210673 TI - The effect of a diabetes education programme (PRIMAS) for people with type 1 diabetes: results of a randomized trial. AB - OBJECTIVE: In a randomized, multi-centre trial, the efficacy of a self-management oriented education programme (PRIMAS) for people with type 1 diabetes was compared with an established education programme as control group (CG). Primary outcome was the effect on glycaemic control in a 6-month follow-up. Secondary outcomes were the impact on emotional aspects, self-management related aspects and hypoglycaemia problems. METHODS: The study was conducted in an outpatient setting. 160 participants were randomized. Baseline characteristics in PRIMAS and CG were similar (age 45.1+/-13.5 vs. 45.9+/-13.1 years, p=.716; diabetes duration 18.8+/-12.3 vs. 19.8+/-13.4 years, p=.615; BMI 26.5+/-4.6 vs. 27.5+/-5.0kg/m(2), p=.236; HbA1c 8.3+/-1.1 vs. 8.1+/-1.0%, p=.236). RESULTS: At follow-up there was a significant 0.4 percentage points greater reduction of HbA1c in PRIMAS compared to CG (Delta -0.4+/-1.0% vs. Delta 0.0+/-0.6%; p=.012). Also, diabetes-related distress (Delta -0.3+/-0.7 vs. -0.1+/-0.4, p=.032) and dissatisfaction with diabetes treatment (Delta -3.3+/-6.9 vs. -1.9+/-5.6, p=.024) decreased more in PRIMAS. Diabetes empowerment (Delta 2.6+/-5.9 vs. 0.8+/-5.1, p=.037) and diabetes self-efficacy (Delta 1.4+/-3.6 vs. 0.2+/-4.0, p=.013) increased in PRIMAS. Incidence of severe hypoglycemia, hypoglycemia awareness, diabetes knowledge, and self-care behaviour improved in both groups with no significant differences between groups. CONCLUSION: PRIMAS is more effective in lowering HbA1c than a previously established education programmes and also showed superiority in reducing diabetes-related distress and increasing diabetes empowerment, diabetes self-efficacy and satisfaction with insulin therapy. PMID- 24210675 TI - Comparison of outcomes in patients <=85 versus >85 years of age undergoing transcatheter aortic-valve implantation. AB - The impact of age on baseline characteristics and outcomes in patients with severe aortic stenosis who undergo transcatheter aortic valve implantation (TAVI) has not been thoroughly investigated. To describe the baseline clinical profile of TAVI patients aged >85 and <=85 years and to evaluate the influence of age differences on outcomes, we evaluated a consecutive cohort of 293 patients who underwent transfemoral TAVI at the Tel Aviv Medical Center. The cohort was divided into 2 groups: patients aged >85 years (n = 93) and patients aged <=85 years (n = 200). Mean age was 83 +/- 5.3 years (range 63 to 98) for the entire cohort. Women comprised 70% of the older group and 57.5% of the younger age group (p = 0.043). Baseline clinical profile, including EuroSCORE index and preprocedural aortic valve area were similar in both age groups. Thirty-day mortality, major vascular complications, need for permanent pacemaker implantation, length of hospital stay, and improvement in functional class after the procedure showed no differences between the 2 groups. Adjustment for baseline clinical differences between groups did not change the results. In conclusion, among patients who underwent transfemoral TAVI, older patients (>85 years) experience similar benefits and outcomes regarding functional status, complication rates, and 30-day mortality. PMID- 24210674 TI - Relation of thoracic aortic distensibility to left ventricular area (from the Multi-Ethnic Study of Atherosclerosis [MESA]). AB - Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography, a marker of LV remodeling, has not been well demonstrated. The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased LV area. The study population consisted of 3,540 patients (mean age 61 +/- 10 years, 46% men) from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent aortic distensibility (AD) assessment on magnetic resonance imaging and LV area measurement on computed tomography (adjusted to body surface area). Multivariate logistic regression was performed to assess the association between body surface area-normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical, and imaging covariates. Mean LV area index was 2,153 cm(2), and mean AD was 1.84 * 10(3) mm Hg(-1). Subjects in the lowest AD quartile were older, with higher prevalence rates of hypertension, diabetes, and hypercholesterolemia (p <0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium, and C-reactive protein, each SD decrease was associated with an 18-cm(2) increase in LV area. In addition, decreasing AD quartiles were independently associated with increasing LV area index, defined as >75th percentile. In conclusion, in this multiethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area. PMID- 24210676 TI - Age-specific analyses of breast cancer versus heart disease mortality in women. PMID- 24210677 TI - Frequency of radial artery occlusion after transradial access in patients receiving warfarin therapy and undergoing coronary angiography. AB - The efficacy of warfarin-induced anticoagulation in reducing radial artery occlusion (RAO) after transradial access is not known. The present case-control study compared the incidence of early (24 hours) and late (30 days) RAO in patients undergoing transradial diagnostic coronary angiography during therapeutic warfarin anticoagulation (group 1) with that of a matched (3:1) cohort of patients not receiving warfarin and receiving intraprocedural heparin (group 2). All patients underwent transradial diagnostic coronary angiography using a 5F hydrophilic introducer sheath. The patients in group 2 received an intravenous heparin bolus (50 IU/kg) immediately after sheath insertion. After sheath removal, hemostasis was obtained using the TR-band (Terumo Interventional Systems, Terumo Medical, Tokyo, Japan) and a plethysmography-guided patent hemostasis technique. We included 86 patients receiving warfarin with an international normalized ratio of 2 to 4 in group 1 and 250 matched patients in group 2. No significant differences were present in the demographic and procedural variables between the 2 groups. Early RAO occurred in 18.6% of the patients in group 1 compared with 9.6% of patients in group 2 (p = 0.024). The incidence of late RAO remained significantly higher in group 1 compared with group 2 (13.9% vs 5.2%, p = 0.01). All patients with RAO remained asymptomatic. In conclusion, patients receiving chronic oral anticoagulation with warfarin and undergoing transradial coronary angiography without parenteral anticoagulation had a higher incidence of early and late RAO compared with patients receiving standard intravenous heparin therapy. PMID- 24210679 TI - High-density lipoprotein mediated cellular cholesterol efflux in acute coronary syndromes. AB - Systemic inflammation at the development of an acute coronary syndrome (ACS) might alter the high-density lipoprotein (HDL) components and function. One of the major functions of HDL particles is their ability to remove cellular cholesterol from macrophages. The aim of the present study was to characterize the HDL efflux capacity in patients with ACS. We analyzed the cholesterol efflux in those ACS (within 72 hours of symptoms [ACS1]) and, again, 3 months later (ACS2). As controls, we used normal subjects without coronary artery disease (CAD) and patients with chronic, stable CAD. The 4 groups were matched for age and HDL cholesterol levels. We used a cell-based efflux system in (3)[H] cholesterol-labeled J774 macrophages to measure cholesterol efflux from apolipoprotein B-depleted plasma. The present study included 20 patients with ACS. Their mean age was 58 +/- 9 years, and the mean HDL cholesterol level was 1.06 +/- 0.22 mmol/L (41 +/- 9 mg/dl). The ACS1 group showed a marked increase in high-sensitivity C-reactive protein and serum amyloid A, reflecting systemic inflammation. The HDL cholesterol efflux capacity was reduced in ACS1 subjects and remained reduced 12 weeks later and in those with stable CAD. These results suggest that the acute presence of serum amyloid A does not account for the impairment of HDL-mediated cholesterol efflux capacity in the ACS1 group. Little correlation was found between HDL cholesterol and HDL efflux capacity (r = 0.233; p = 0.049), suggesting that HDL cholesterol is a poor marker of HDL function in inflammatory states and CAD. In conclusion, our data support the concept that atherogenic HDL dysfunction and impaired efflux occur in ACS, independent of changes in plasma HDL cholesterol and apolipoprotein A-I levels. PMID- 24210678 TI - Renal artery calcium, cardiovascular risk factors, and indexes of renal function. AB - Vascular calcium is well studied in the coronary and peripheral arteries, although there are limited data focusing on calcium deposits specific to renal arteries. The associations among renal artery calcium (RAC), cardiovascular disease risk factors, and indexes of renal function are unknown. We examined 2,699 Framingham Heart Study participants who were part of a multidetector computed tomography substudy from 2008 to 2011. RAC was measured as a calcified plaque of >130 HU and an area of >3 contiguous pixels. Detectable RAC was defined as an Agatston score >0. Chronic kidney disease was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Microalbuminuria was defined as an albumin/creatinine ratio of >=17 mg/g for men and >=25 mg/g for women. Multivariable adjusted logistic regression models were used to evaluate the associations between RAC, cardiovascular disease risk factors, and renal function. The associations were secondarily adjusted for coronary artery calcium (CAC) that was used as a marker of nonrenal systemic vascular calcium. The prevalence of RAC was 28.2%; this was similar in women (28.8%) and men (27.5%). Patients with RAC had a higher odds of microalbuminuria (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.22 to 2.61, p = 0.003), hypertension (OR 2.11, 95% CI 1.69 to 2.64, p <0.001), and diabetes (OR 1.60, 95% CI 1.14 to 2.24, p = 0.01) but not chronic kidney disease (OR 0.87, 95% CI 0.58 to 1.32). After adjustment for CAC, the association with microalbuminuria and hypertension persisted, but the association with diabetes became nonsignificant. In conclusion, RAC is common and independently associated with microalbuminuria and hypertension after adjustment for nonrenal vascular calcium. RAC may be uniquely associated with these markers of renal end-organ damage. PMID- 24210680 TI - Fatty acids and recovery during first hours of acute myocardial ischemia. PMID- 24210681 TI - gamma375W fibrinogen-synthesizing CHO cells indicate the accumulation of variant fibrinogen within endoplasmic reticulum. AB - BACKGROUND: Hepatic endoplasmic reticulum (ER) storage disease (HERSD) associated with hypofibrinogenemia has been reported in patients with four types of heterozygous gamma-chain variant fibrinogen in the C terminal region. Of interest, substitution of gammaR375W induced hypofibrinogenemia and HERSD, whereas gammaR375G induced dysfibrinogenemia. OBJECTIVES: To analyze the synthesis of variant fibrinogen and morphological characteristics, we established variant fibrinogen-producing cells and compared them with wild-type fibrinogen synthesizing cells. METHODS: The fibrinogen gamma-chain expression vectors coding gamma375W and gamma375G were altered by oligonucleotide-directed mutagenesis and transfected into Chinese hamster ovary (CHO) cells. Synthesis of fibrinogen (media and cell lysates) was measured by ELISA for each cloned cell line and morphological characteristics were observed by immunofluorescence and transmission electron microscopy. RESULTS: The medium/cell lysate fibrinogen ratio of gamma375W-CHO cells was markedly lower than that of the normal cells and gamma375G-CHO cells. Immunostaining with anti-fibrinogen antibody showed only gamma375W-CHO cells, but revealed two types of cells containing cytoplasmic inclusion bodies, scattered large-granular bodies and fibrous forms. Observation by confocal microscopy indicated that both inclusion bodies were colocalized with fibrinogen and ER-membrane protein; furthermore, transmission electron microscopic observation demonstrated dilatation of the ER by large-granular inclusion bodies and fibrous forms filled with regularly structured fibular materials within the dilated ER. CONCLUSION: These results demonstrated that assembled and non-secreted gamma375W fibrinogen was accumulated in the dilated ER and aggregated variant fibrinogen was seen as regularly structured fibular materials, which was similar to the fingerprint-like pattern observed at inclusion bodies in patients' hepatocytes affected with HERSD. PMID- 24210682 TI - The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. AB - The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB2). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB2 is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB2 receptor dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions. PMID- 24210683 TI - Caffeinated alcohol consumption profiles and associations with use severity and outcome expectancies. AB - Growing evidence suggests that the consumption of caffeinated alcoholic beverages (CAB) may be riskier than alcohol alone. Efforts to identify patterns of CAB use and the correlates of such drinking patterns could further our conceptualization of and intervention for this health issue. Consequently, the current study aimed to (1) identify distinct classes of CAB users, (2) examine differences between classes on measures of alcohol and caffeine problems, and (3) compare distinct classes of CAB users on caffeine and alcohol outcome expectancies. Participants were 583 (31% men) undergraduate students from a psychology research pool. Latent profile analysis models were derived using four indicators: CAB use quantity, CAB use frequency, alcohol use quantity, and alcohol use frequency. Finding revealed four classes of drinkers: High Alcohol/High CAB (6.00%), High Alcohol/Moderate CAB (5.15%), High Alcohol/Low CAB (22.99%), and Low Alcohol/Low CAB (65.87%). The Low Alcohol/Low CAB class reported the lowest relative levels of caffeine dependence symptoms, caffeine withdrawal, alcohol use problems, and heavy episodic drinking frequency. Further, results indicated differential expectancy endorsement based on use profiles. CAB users in the High Alcohol/Low CAB class endorsed more positive alcohol expectancies than the Low Alcohol/Low CAB group. Those in the High Alcohol/High CAB class endorsed stronger withdrawal symptom caffeine expectancies than all other classes. Inclusion of substance-specific expectancies into larger theoretical frameworks in future work of CAB use may be beneficial. Findings may inform intervention efforts for those at greatest risk related to CAB consumption. PMID- 24210684 TI - Ultrasound evaluation of synovitis in RA: correlation with clinical disease activity and sensitivity to change in an observational cohort study. AB - OBJECTIVE: To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS: One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS: In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r = 0.41, P < 0.0001). The same was true for the PwD score (r = 0.41, P < 0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r = 0.54, P < 0.0001 and r = 0.46, P < 0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS: The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist. PMID- 24210685 TI - PSORS1C1/CDSN is associated with ankylosing spondylitis. PMID- 24210686 TI - Spontaneous atlantoaxial dislocation in ankylosing spondylitis. PMID- 24210687 TI - Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs. AB - Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis. PMID- 24210688 TI - The role of the VEGF-C signaling pathway in preeclampsia? PMID- 24210689 TI - Further results on delay-range-dependent stability with additive time-varying delay systems. AB - In this paper, new conditions for the delay-range-dependent stability analysis of time-varying delay systems are proposed in a Lyapunov-Krasovskii framework. Time delay is considered to be time-varying and has lower and upper bounds. A new method is first presented for a system with two time delays, integral inequality approach (IIA) used to express relationships among terms of Leibniz-Newton formula. Constructing a novel Lyapunov-Krasovskii functional includes information belonging to a given range; new delay-range-dependent criterion is established in term of linear matrix inequality (LMI). The advantage of that criterion lies in its simplicity and less conservative. This paper also presents a new result of stability analysis for continuous systems with two additive time-variant components representing a general class of delay with strong application background in network-based control systems. Resulting criteria are then expressed in terms of convex optimization with LMI constraints, allowing for use of efficient solvers. Finally, three numerical examples show these methods reducing conservatism and improving maximal allowable delay. PMID- 24210690 TI - [Analysis of medications dispensed to control the main cardiovascular risks in the Murcia Region: are there gender differences?]. AB - OBJECTIVES: To estimate the use of cardiovascular medicines and its distribution by age and sex. DESIGN: Observational study. SETTING: Region of Murcia. MAIN MEASUREMENTS: Daily doses of cardiovascular drugs prescribed and dispensed in all the pharmacies of the Region per 1,000 inhabitants-day (DHD). A comparison was made of consumption rates (DHD) by age and sex. RESULTS: The probability of receiving antiplatelet drugs increases with age, with the proportion of men being higher. The use of beta-blockers and angiotensin II increases with age up to 79 years, with an increased consumption in men up to 65 years. The probability of receiving treatment with calcium channel blockers, ACE inhibitors, or statins, linearly increases with age, and the proportion of men under treatment exceeds that of women in the early ages, tending to equalize beyond 80 years. CONCLUSIONS: This study shows that the cardiovascular disease prevention focuses on people aged 40 to 74 years. Access by women to cardiovascular therapy occurs with a delay of 3-5 years, depending on the treatment subgroup. Changes should be promoted to encourage rational and equitable access and use of the drugs. PMID- 24210691 TI - VACTERL (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies) association: disease spectrum in 25 patients ascertained for their upper limb involvement. AB - OBJECTIVE: To review the clinical characteristics in a series of 25 patients with VACTERL (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies) association who were ascertained for upper limb involvement. STUDY DESIGN: The study involved a review of clinical and radiologic data from patients with VACTERL association collected by a hand surgery clinic between 2004 and 2013. RESULTS: Radial axis involvement was found in all 25 patients (100%), with severe thumb function impairment in 79% and complete absence of the radius in roughly 33%. Costovertebral anomalies were the most frequent feature, found in 23 patients (92%). All 3 core features (anal atresia, tracheoesophageal fistula with esophageal atresia, and costovertebral anomalies) were present in only 12% of the patients. Twelve patients (48%) had abnormalities not part of the VACTERL spectrum, showing a specific pattern of non-VACTERL-type malformations, including genitourinary abnormalities (12%), single umbilical artery (8%), and tethered cord (8%). Previously unreported clinical findings were concurrent hypoplasia of both the odontoid process and the coccyx in 2 patients and an isolated sacral dimple in 2 patients. CONCLUSION: Upper limb involvement in VACTERL association is a specific feature of the radial axis that occurs in monolateral form in approximately 75% of cases and, when bilateral, always occurs in a nonsymmetrical fashion. Odontoid and coccygeal hypoplasia and sacral dimple are newly reported malformations of the VACTERL phenotype. PMID- 24210692 TI - The ameliorating effects of 2,3-dihydroxy-4-methoxyacetophenone on scopolamine induced memory impairment in mice and its neuroprotective activity. AB - We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study. The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4 methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive enhancing effect on scopolamine-induced amnesia in mice. Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy 4-methoxyacetophenone (50mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC50 value: 10.94MUM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca(2+)] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive enhancing activities through its antioxidant activity. We suggest that 2,3 dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer's disease. PMID- 24210693 TI - Relationship between metabolic cost and muscular coactivation across running speeds. AB - OBJECTIVES: Muscular coactivation can help stabilise a joint, but contrasting results in previous gait studies highlight that it is not clear whether this is metabolically beneficial. The aim was to assess the relationship between the metabolic cost of running and muscular coactivation across different running speeds, in addition to assessing the reliability and precision of lower limb muscular coactivation. DESIGN: Eleven female recreational runners visited the laboratory on two separate occasions. On both occasions subjects ran at three speeds (9.1, 11 and 12 km h(-1)) for six minutes each. METHODS: Oxygen consumption and electromyographic data were simultaneously recorded during the final two minutes of each speed. Temporal coactivations of lower limb muscles during the stance phase were calculated. Five muscles were assessed: rectus femoris, vastus lateralis, biceps femoris, tibialis anterior and gastrocnemius lateralis. RESULTS: Nonparametric correlations revealed at least one significant, positive association between lower limb muscular coactivation and the metabolic cost of running for each speed. The length of tibialis anterior activation and muscular coactivation of the biceps femoris-tibialis anterior and gastrocnemius lateralis-tibialis anterior decreased with speed. CONCLUSIONS: These results show that longer coactivations of the proximal (rectus femoris-biceps femoris and vastus lateralis-biceps femoris) and leg extensor (rectus femoris-gastrocnemius lateralis) muscles were related to a greater metabolic cost of running, which could be detrimental to performance. The decrease in coactivation in the flexor and distal muscles at faster speeds occurs due to the shorter duration of tibialis anterior activation as speed increases, yet stability may be maintained. PMID- 24210694 TI - [It's time to take a firm step forward]. PMID- 24210695 TI - Ultrasonic assisted arsenate adsorption on solvothermally synthesized calcite modified by goethite, alpha-MnO2 and goethite/alpha-MnO2. AB - A highly porous calcium carbonate (calcite; sorbent 1) was used as a support for modification with alpha-FeOOH (calcite/goethite; sorbent 2), alpha-MnO2 (calcite/alpha-MnO2; sorbent 3) and alpha-FeOOH/alpha-MnO2 (calcite/goethite/alpha-MnO2; sorbent 4) in order to obtain a cheap hybrid materials for simple and effective arsenate removal from aqueous solutions. The adsorption ability of synthesized adsorbents was studied as a function of functionalization methods, pH, contact time, temperature and ultrasonic treatment. Comparison of the adsorptive effectiveness of synthesized adsorbents for arsenate removal, under ultrasound treatment and classical stirring method, has shown better performance of the former one reaching maximum adsorption capacities of 1.73, 21.00, 10.36 and 41.94 mg g(-1), for sorbents 1-4, respectively. Visual MINTEQ equilibrium speciation modeling was used for prediction of pH and interfering ion influences on arsenate adsorption. PMID- 24210696 TI - Medullary hemangioblastoma: 34 patients at a single institution. AB - This study aimed to elucidate the surgical experience of medullary hemangioblastoma (MH) at a single institution. We reviewed 34 consecutive patients with MH operated on between January 2005 and June 2012 in the neurosurgery department of the Beijing Tiantan Hospital. There were 14 men and 20 women. The patients were aged from 17 to 60 years with an average age of 38 years. Tumors were cystic in 12 patients (Type A), and solid in 22 patients. The solid tumors were of a small size in six patients (<3 cm, Type B), large in 12 (3.1-5 cm, Type C), and giant in four (>5 cm, Type D). Radical tumor removal was achieved in all patients. Tracheotomy was performed in 10 patients (one Type B patient, seven Type C, two Type D) postoperatively. Pneumonia secondary to lower cranial nerve palsy occurred in six patients (all Type C). Complications including intracranial infection (n=5), gastrointestinal bleeding (n=2), and intracranial hematoma (n=1) also occurred in this group. Follow-up (range, 2-82 months; mean, 30 months) was available in all patients. At follow-up, 29 patients (85.3%) had a good outcome. Twenty-eight of these (82.4%) had an excellent outcome postoperatively (Karnofsky Performance Status ? 80). Although transient surgical complications are possible especially for large solid tumors, total surgical resection can be performed with favorable long-term outcomes with meticulous microsurgical technique and understanding of the vascular pattern of the tumor. Postoperative management of MH is as important as the operation. PMID- 24210697 TI - Decline in acute urinary toxicity: a long-term study in 2011 patients with prostate brachytherapy within a provincial institution. AB - PURPOSE: To determine whether acute urinary toxicity rates improve with the overall experience of a large prostate brachytherapy program. METHODS AND MATERIALS: From 1998 to 2009, 2937 patients were treated with prostate brachytherapy at the British Columbia Cancer Agency. Baseline patient, treatment, and implant factors were recorded prospectively. Acute urinary toxicity data were prospectively recorded at baseline and each follow-up visit. Patients with >=2 years of follow-up data were grouped into cohorts of 500 for analysis. RESULTS: Two thousand eleven patients met the above criteria. Acute urinary retention (AUR) in the acute period (within 6 months of implant) occurred in 9.1% of patients overall and was prolonged (catheterization >20 days) in 3.4%. Both overall AUR and prolonged AUR decreased across implant cohorts (p <= 0.001 in both cases). Overall acute Radiation Therapy Oncology Group (RTOG) Grades 0 and 1 urinary toxicity rate was 57.5% and RTOG Grades 2 and 3 urinary toxicity rates were 34.3% and 8.1%, respectively. Acute toxicity improved over time for both RTOG Grades >=2 and >=3 toxicity (p < 0.0001). International prostate symptom score resolution to baseline was achieved in 80.5% of patients with a median time of 12.2 months. CONCLUSIONS: Acute AUR and RTOG urinary toxicity rates continue to decline with the increasing experience of our provincial prostate brachytherapy program, despite its expansion to new centers and addition of members. This is likely due to better patient selection, refinement in treatment planning and implantation technique, and mentorship and training process. PMID- 24210698 TI - Perioperative image-adapted brachytherapy for the treatment of paranasal sinus and nasal cavity malignancies. AB - PURPOSE: Sinonasal malignancies are a rare group of cancers often associated with late presentation and poor prognosis. In the past, there was little progress regarding survival rate, and often, multimodal treatment regimens are required. The aim of this study was to evaluate the clinical outcome of perioperative image adapted brachytherapy (IABT) as part of a multidisciplinary treatment regimen for the therapy of sinonasal cancer. METHODS AND MATERIALS: Since 2006, patients with sinonasal cancer at the University Hospital of Schleswig-Holstein Campus Luebeck, Germany, were offered a multimodal treatment concept including head and neck surgery, perioperative IABT with or without external beam radiation therapy, and chemotherapy. In a retrospective study, such patients were analyzed for survival rate, tumor control, and toxicity of the interdisciplinary treatment. RESULTS: Thirty-five consecutive patients were analyzed. The majority of patients (63%) were treated for a primary tumor and 62% presented with tumor Stages III-IV. The mean follow-up time with IABT was 28 months. Overall survival estimate was 72% after 3 years. Disease-specific survival, disease-free survival, and local control rates were 83%, 63%, and 67%, respectively. On univariate analysis, a significant better disease-free survival rate was found in patients treated for primary, but not recurrent, sinonasal cancer (p = 0.006). The overall treatment toxicities were mainly classified Grade I. CONCLUSIONS: Interdisciplinary perioperative IABT is associated with excellent locoregional control and survival rates. IABT is well tolerated and shows low toxicity. Furthermore, visual acuity can be preserved in advanced cases. The implementation of perioperative IABT into multimodal treatment regimens improves the oncologic outcome. PMID- 24210699 TI - The absence of Ku but not defects in classical non-homologous end-joining is required to trigger PARP1-dependent end-joining. AB - Classical-non-homologous end-joining (C-NHEJ) is considered the main pathway for repairing DNA double strand breaks (DSB) in mammalian cells. When C-NHEJ is defective, cells may switch DSB repair to an alternative-end-joining, which depends on PARP1 and is more erroneous. This PARP1-EJ is suggested to be active especially in tumor cells contributing to their genomic instability. Here, we define conditions under which cells would switch the repair to PARP1-EJ. Using the end jining repair substrate pEJ, we revealed that PARP1-EJ is solely used when Ku is deficient but not when either DNA-PKcs or Xrcc4 is lacking. In the latter case, DSB repair, however, could be shuttled to PARP1-EJ after additional Ku80 down-regulation, which partly rescued the DSB repair in these mutants. We demonstrate here that PARP-EJ may work on DSB ends at high fidelity manner, as evident from the unchanged efficiency upon blocking end resection by either roscovitin or mirin. Furthermore, we demonstrate for that PARP-EJ is likewise involved in the repair of multiple DSBs (I-PpoI- and IR-induced). Importantly, we identified a chromatin signature associated with the switch to PARP1-EJ which is characterized by a strong enrichment of both PARP1 and LigIII at damaged chromatin. Together, these data indicate that Ku is the main regulator for the hierarchal organization between C-NHEJ and PARP1-EJ. PMID- 24210700 TI - Endogenous levels of Rad51 and Brca2 are required for homologous recombination and regulated by homeostatic re-balancing. AB - Stable expression of Rad51 siRNA was used to generate mouse hybridoma cell lines in which endogenous Rad51 levels were depleted by as much as 60%. Stable Rad51 knockdowns feature reduced homologous recombination responses. The relative ease with which stable Rad51 knockdowns were recovered was surprising, given the embryonic lethality of Rad51 ablation. Interestingly, Rad51-depleted hybridoma cell lines are characterized by reduced levels of p53 protein. Completely unexpected, was the finding that Rad51-depleted hybridoma cell lines are also reduced for the breast cancer susceptibility 2 (Brca2) protein. Additionally, hybridoma cell lines that are siRNA depleted for mouse Brca2 show a corresponding reduction in Rad51 and p53 proteins. Furthermore, cellular levels of Rad51, Brca2 and p53 can be elevated in these cell lines by ectopic expression of wild-type human Rad51 and wild-type human BRCA2. In marked contrast, hybridoma cell lines that are siRNA depleted for mouse p53 feature relatively normal Rad51 and Brca2 levels. These results suggest that cellular levels of Brca2 and Rad51 are mutually dependent on each other, and that low levels of these proteins provide selective pressure for reduction of p53, which permits cell growth. PMID- 24210701 TI - Lung transplantation: SEPAR year 2013. PMID- 24210703 TI - A single institution's effort to translate codeine knowledge into specific clinical practice. AB - BACKGROUND: Codeine is an unpredictable analgesic because of its variable pharmacokinetic, pharmacodynamic, and pharmacogenetic properties. This variability may lead to ineffective analgesia in some and respiratory depression in others. Despite this, codeine is still widely used. At a pediatric tertiary medical institution, codeine was prescribed despite efforts to inform prescribers of the potentially unpredictable analgesia and serious side effects. MEASURES: A retrospective/prospective metric was introduced to determine the frequency of codeine orders as compared with similar institutions using Pediatric Health Information Systems data. INTERVENTION: Interventions included formal and informal education to prescribers, and replacing codeine with oxycodone for patients aged older than six months and an age-appropriate medication for those patients younger than six months within ordersets. Identifying and addressing the major barriers to change also was a key part of the process. OUTCOMES: Codeine use was reduced by 97% from the first quarter of 2008 through the third quarter of 2012. This was accomplished through orderset changes and education. Codeine was completely eliminated from the hospital formulary in January 2013. CONCLUSIONS/LESSONS LEARNED: This quality improvement initiative was successful in eliminating codeine from the hospital formulary. Although education decreased codeine orders, understanding and addressing the barriers to change and directly changing the ordersets were the most effective and efficient for knowledge translation. PMID- 24210702 TI - Supportive cryotherapy: a review from head to toe. AB - CONTEXT: Conventional chemotherapy leads to multiple adverse mucocutaneous complications such as oral mucositis, alopecia, ocular toxicity, and onycholysis. Limited pharmacologic interventions are available for preventing these clinical problems. OBJECTIVES: This study aimed to critically review the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms. METHODS: A narrative review was performed, with an emphasis on randomized controlled trials. A comprehensive search using PubMed, Ovid, Embase, and MEDLINE((r)) was completed. References of all cited articles also were reviewed. Data from the review were composed of articles published between 1970 and May 2013. RESULTS: Available evidence suggests that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity, and onycholysis. The major limitations of studies include the absence of blinded control groups and variable clinical end points. CONCLUSION: Regional hypothermia decreases the burden of these four chemotherapy-induced complications and is well tolerated. More research is needed to determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, the ideal duration of cooling needed, and further improve the ease of use of the cooling devices. PMID- 24210704 TI - Factors associated with survival after opioid rotation in cancer patients presenting to an outpatient supportive care center. AB - CONTEXT: Data on cancer outpatients undergoing opioid rotation (OR) are limited. Understanding the characteristics of patients who do not follow up after OR could facilitate optimization of OR. OBJECTIVES: To compare the characteristics and overall survival of patients with and without follow-up after OR. METHODS: In this preliminary ad hoc analysis, we reviewed consecutive patients who presented to our supportive care center in 2008 for OR. Data about demographics, scores on the Edmonton Symptom Assessment System and Memorial Delirium Assessment Scale (MDAS), opioid use, and indications for OR were collected. Univariate logistic regression models were used to determine the factors associated with follow-up. Kaplan-Meier curves were used to evaluate survival. RESULTS: Of the 190 patients who underwent OR, 120 (63%) had a follow-up visit. Follow-up visits occurred more frequently in patients with localized disease (89%; 24/27; P = 0.0023), history of substance abuse (100%; 12/12; P = 0.0085), performance status <= 2 (66%; 97/146; P = 0.0002), no delirium (67%; 118/177; P = 0.002), and uncontrolled pain as reason for OR (66%; 97/146; P = 0.036). Patients who underwent OR for opioid induced neurotoxicity (44%; 15/34; P = 0.01) and had higher MDAS scores (P = 0.0009) were less likely to follow up. Both follow-up after OR (P < 0.001) and successful OR (P = 0.012) were associated with longer overall survival, with a difference in median survival of 4.3 and 3 months, respectively. CONCLUSION: Our preliminary study suggests that patients with advanced cancer, poorer performance status, opioid-induced neurotoxicity, and higher MDAS scores are less likely to follow up after OR and may have shorter overall survival and, therefore, require closer follow-up. Patients with unsuccessful OR also may have a shorter overall survival. Further studies are warranted. PMID- 24210706 TI - Serial prognostication: a new look at an old tool. PMID- 24210705 TI - A randomized trial of weekly symptom telemonitoring in advanced lung cancer. AB - CONTEXT: Lung cancer patients experience multiple, simultaneous symptoms related to their disease and treatment that impair functioning and health-related quality of life (HRQL). Computer technology can reduce barriers to nonsystematic, infrequent symptom assessment and potentially contribute to improved patient care. OBJECTIVES: To evaluate the efficacy of technology-based symptom monitoring and reporting in reducing symptom burden in patients with advanced lung cancer. METHODS: This was a prospective, multisite, randomized controlled trial. Two hundred fifty-three patients were enrolled at three sites and randomized to monitoring and reporting (MR) or monitoring alone (MA). Patients completed questionnaires at baseline, 3, 6, 9, and 12 weeks and symptom surveys via interactive voice response weekly for 12 weeks. MR patients' clinically significant symptom scores generated an e-mail alert to the site nurse for management. The primary endpoint was overall symptom burden; secondary endpoints included HRQL, treatment satisfaction, symptom management barriers, and self efficacy. RESULTS: This randomized controlled trial failed to demonstrate efficacy of symptom monitoring and reporting in reducing symptom burden compared with monitoring alone in lung cancer. HRQL declined over 12 weeks in both groups (P < 0.006 to P < 0.025); at week 12, treatment satisfaction was higher in MA than MR patients (P < 0.012, P < 0.027). Adherence to weekly calls was good (82%) and patient satisfaction was high. CONCLUSION: Feasibility of using a technology based system for systematic symptom monitoring in advanced lung cancer patients was demonstrated. Future research should focus on identifying patients most likely to benefit and other patient, provider, and health system factors likely to contribute to the system's success. PMID- 24210707 TI - Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. AB - OBJECTIVES: To conduct a systematic literature review on incidence and prevalence of juvenile idiopathic arthritis and to estimate these figures in Europe for 2010. METHODS: Articles on incidence or prevalence of juvenile idiopathic arthritis were searched in Medline. Pooled incidence and prevalence were calculated overall, by gender, age, classification and arthritis categories. We used the available age and gender pooled rates to standardize the incidence and prevalence on the 2010 European population and estimate the number of cases in Europe in 2010. RESULTS: Forty-three articles (33 on incidence, 29 on prevalence) were included. Incidence rates varied from 1.6 to 23 and prevalence from 3.8 to 400/100,000. Pooled incidence and prevalence were higher for girls (10.0 [9.4 10.7] and 19.4 [18.3-20.6]/100,000) than boys (5.7 [5.3-6.2] and 11.0 [10.2 11.9]/100,000). Oligoarthritis was the most frequent form (pooled incidence rate 3.7 [3.5-3.9] and prevalence 16.8 [15.9-17.7]/100,000). The direct standardized incidence rate was 8.2 [7.5-9.0] and prevalence 70.2 [62.9-78.1]/100,000. In Europe in 2010, the estimated number of incident cases was 6896 [5481-8578] and 59,175 [44,256-76,983] prevalent cases. CONCLUSIONS: Incidence and prevalence varied greatly among published reports of juvenile idiopathic arthritis, which may be explained by methodological issues, classification used, and time. Estimating the number of affected children can be useful, especially with the new treatment possibilities. PMID- 24210708 TI - Missing data in longitudinal studies: cross-sectional multiple imputation provides similar estimates to full-information maximum likelihood. AB - PURPOSE: The aim of this research was to examine, in an exploratory manner, whether cross-sectional multiple imputation generates valid parameter estimates for a latent growth curve model in a longitudinal data set with nonmonotone missingness. METHODS: A simulated longitudinal data set of N = 5000 was generated and consisted of a continuous dependent variable, assessed at three measurement occasions and a categorical time-invariant independent variable. Missing data had a nonmonotone pattern and the proportion of missingness increased from the initial to the final measurement occasion (5%-20%). Three methods were considered to deal with missing data: listwise deletion, full-information maximum likelihood, and multiple imputation. A latent growth curve model was specified and analysis of variance was used to compare parameter estimates between the full data set and missing data approaches. RESULTS: Multiple imputation resulted in significantly lower slope variance compared with the full data set. There were no differences in any parameter estimates between the multiple imputation and full information maximum likelihood approaches. CONCLUSIONS: This study suggested that in longitudinal studies with nonmonotone missingness, cross-sectional imputation at each time point may be viable and produces estimates comparable with those obtained with full-information maximum likelihood. Future research pursuing the validity of this method is warranted. PMID- 24210709 TI - [Screening and diagnosis of small for gestational age fetuses]. AB - OBJECTIVE: Define the mode of screening and diagnosis of fetal small for gestational age (SGA). METHODS: Bibliographic research by consulting Pubmed database and guidelines of the international professional societies. Keywords used: Intra uterine growth retardation or restriction, small for gestational age, curve, chart, fetal biometry, screening, velocity, fundal height measurement. RESULTS: The performance of ultrasound to detect SGA is low. The mode of screening and diagnosis of SGA must be well defined to be consensual. The fundal height measurement keeps its place in the screening from 22SA (grade C). The criteria for measuring ultrasound parameters defined by the comite technique d'echographie are recommended (professional agreement). They allow the calculation of the estimated fetal weight (EFW). That must be transferred to the reference curve adopted (professional agreement). The introduction of audit on techniques for measuring ultrasound parameters should be encouraged (grade B). CONCLUSION: Fetal biometry must be interpreted according to the clinical context and ultrasound including Doppler (grade C). To improve the performance of ultrasound, there is no need to another ultrasound examination in late pregnancy (grade A) except after a clinical suspicion (grade C). The minimum interval between two biometric tests is 3 weeks (grade B). This interval may be lower if the EFW is important in the decision of any fetal extraction (professional consensus). PMID- 24210710 TI - [Recommendations for clinical practice: Presumed benign ovarian tumors--short text]. AB - These guidelines from the French College of Gynecologists and Obstetricians on the diagnosis and treatment of presumed benign ovarian tumors (PBOT) concern physicians whether gynecologists, obstetricians, surgeons, radiologists, pediatricians, and general practitioners. Vaginal pelvic ultrasound is the first line imaging examination in case of PBOT in adult women (grade A). In case of pure fluid unilocular mass less than 7 cm size, ultrasound is sufficient to characterize the mass (grade A). MRI is recommended as second-line to explore indeterminate masses or masses greater than 7 cm (grade B). Serum CA125 assay is not recommended as first-line diagnostic in adult women (grade C). Among women with a pure unilocular liquid cyst, hormonal therapy is ineffective (LE1) and is not recommended (grade A). Ultrasound-guided puncture is not recommended (grade B). In adult women without history of cancer, abstention is possible in case of asymptomatic pure unilocular cyst less than 10 cm (grade B). If symptoms develop, laparoscopy is the reference approach for PBOT surgical treatment (grade A). A conservative surgical treatment (cystectomy) should be preferred to oophorectomy in non-menopausal women without previous history of cancer (grade C). In cases of suspected adnexal torsion, laparoscopic surgical exploration is recommended (grade B). Conservative treatment, untwisting without oophorectomy, is recommended for non-menopausal women whatever the estimated duration of the twist and the macroscopic appearance of the ovary (grade B). During pregnancy, expectation is recommended for asymptomatic unilocular liquid masses less than 6 cm (grade C). PMID- 24210711 TI - [Intra uterine growth retardation: guidelines for clinical practice--Method and organization]. PMID- 24210712 TI - [Intra uterine growth retardation: guidelines for clinical practice- Introduction]. PMID- 24210713 TI - [Prevention of the complications related to hysteroscopy: text of guidelines for clinical practice--Synthesis]. PMID- 24210714 TI - [Definitions: small for gestational age and intrauterine growth retardation]. AB - OBJECTIVES: Screening for intrauterine growth restriction (IUGR) is a major component of antenatal care, but the debate about the choice of birthweight standards is longstanding. The objective of this first chapter is to provide guidelines about optimal definition of IUGR. MATERIALS AND METHODS: Literature review about available birthweight curves to define IUGR, including the analysis of their diagnosis accuracy and their relevance to identify babies at risk of poor perinatal outcomes. RESULTS: Intrauterine growth curves are more suitable for "normal" growth modeling than birth weight curves, and fetal growth is influenced by individual characteristics, fetal gender being the most important among them (EL2). Infants with a low birth weight are either constitutionally small babies or babies with pathological fetal growth failure. Use of "SGA" for all Small for Gestational Age infants is now recommended, "IUGR" being appropriate only for infants with pathological growth restriction (Professional consensus). Depending on reference curves, identified SGA babies and pregnancy outcomes may be different. Customized birth weight standards are based on an intrauterine growth modeling adjusted for fetal gender, maternal height, weight and parity, and appear to be the most accurate to identify SGA births at risk (EL3). However, their benefit on perinatal morbidity and mortality has not been demonstrated by prospective studies. CONCLUSION: Benefits and drawbacks of customized birth weight curves seem in favor of their use. Their application in ante and postnatal investigations is a real opportunity to standardize clinical practice and make information provided to parents more consistent. PMID- 24210715 TI - [Short-term outcome and small for gestational age newborn management]. AB - OBJECTIVE: To describe early complications and management of the small for gestational age (SGA) neonate. METHODS: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations. Words included in the search mainly were: small for gestational age, intrauterine growth restriction, fetal growth restriction, very low birth weight infants, neonatal management, neonatal outcome, neonatal morbidity, neonatal mortality RESULTS: Neonatal mortality relative risk among SGA infants is 2-4 times higher than adapted for gestational age (AGA) newborn infants, at any gestational age. SGA infants had an increased risk for perinatal asphyxia, hypothermia and hypoglycaemia during their first days of life. In the SGA preterm population, bronchopulmonary dysplasia, pulmonary hypertension and necrotising enterocolitis are significantly more frequent as compared with AGA population. Periventricular leukomalacia is not significantly different between SGA and AGA infants whereas intraventricular hemorrhage and retinopathy risks are discussed. Adaptive problems require paediatric contact before birth. Early management of the small for gestational age includes intervention to prevent hypothermia, the use of pressure controlled ventilator if needed, and close blood glucose monitoring. CONCLUSIONS: SGA infants had excess neonatal mortality and morbidity in comparison with adapted ones for gestational age (AGA) infants, especially for preterm infants. PMID- 24210716 TI - [Managing and identifying the causes of IUGR]. AB - INTRODUCTION: The management and identification of the causes for a small for gestational age (SGA) and/or an intrauterine growth restriction (IUGR) fetus is a common but complex problem in Obstetrics. MATERIALS AND METHODS: The Medline, Embase and the Cochrane Library databases were examined over the last 15 years, with no language restrictions, using a combination of the words PAG (SGA), IUGR (IUGR), fetal weight (Fetal weight), sonography (ultrasound), management, cause (etiology), examinations (examinations). Some references not selected by this strategy, but associated with these publications or suggested by members of the working group were also added. The relevant articles were used to establish the text of recommendation following discussion between experts of the working group. RESULTS: Once the diagnosis of SGA is raised (whether on clinical, echocardiographic or Doppler), a management strategy to look for potential causes must be proposed and discussed with parents (Expert reviews). The extent of additional explorations varies depending on the exact presentation of the case (term at diagnosis, severity of anomalies). Additional explorations only make sense if they are likely to change the management of the current pregnancy and particularly to reduce perinatal morbidity and mortality. Explorations have two main objectives: (i) assess fetal vitality and possibilities for continuing the pregnancy in terms of safety for the mother and the foetus; (ii) establish the origin of SGA. The latter is detailed in this chapter recommendation. The earlier and the more severe the biometric anomalies, the more comprehensive the investigations. Maternal symptoms or fetal Doppler anomalies also require urgent management. CONCLUSION: Explorations to establish the origin of SGA and/or IUGR must follow a rigorous and systematic approach. In all cases, the practitioner will provide clear information to parents and collect information including detailed clinical and ultrasound examinations. Additional tests and in particular fetal invasive testing must be performed in some cases after parental consent and according to clinical and sonographic guidance elements. PMID- 24210717 TI - [Treatment strategies in presumed benign ovarian tumors]. AB - Benign ovarian tumors can be separated in three groups: teratoma, unilocular cyst and endometrioma. Laparoscopy should always be preferred for the surgical approach. Before menopause, conservative treatment should be preferred apart from previous oncologic history (breast and ovary). After menopause, the surgical approach (conservative or radical) should be discussed on case-by-case basis. Concerning teratoma, follow-up is one of the options for small cyst (less than 4 to 6 cm). For larger cyst, surgery seems to be justified but there is no definitive argument for this attitude. Concerning unilocular cyst, hormonal treatment or ultrasound-guided puncture are not recommended. For symptomatic patient, laparoscopic surgery is the gold standard. For asymptomatic patient, there is no definitive argument for systematic surgery. There is no justification for systematic ultrasound follow-up. For cyst larger than 10 cm, the data in the literature are very poor and surgery can be proposed. Concerning endometrioma, there isn't strong data that allows preferring one treatment (surgical, medical, follow-up) over another. Preoperative medical treatment is not recommended. Stripping technique is the gold standard. Hormonal postoperative treatment is recommended (if there is no desire for pregnancy). PMID- 24210718 TI - [Placental features in intrauterine growth retardation]. AB - OBJECTIVE: To evaluate the placental pathological patterns in intrauterine growth restriction (IUGR) in order to determinate which placental lesions are linked to clinically significant anomalies and to predict the child outcome and the mother risk of recurrence. METHODS: Bibliographic review using the Medline and PubMed databases. RESULTS: Placental studies designed in order to provide macroscopic and microscopic information about the mechanism of IUGR are not numerous and retrospective; files are most of the time very small. Meta-analyses are an exception. Maternal vascular underperfusion is admitted to be the most frequent etiology of IUGR. None of the associated placental lesions is pathognomonic but the combination of a number of placental changes is. Low placental weight and microscopic lesions are more frequent than gross anomalies. Other pathophysiological groups of placental pathologies are reported to be linked to fetal growth restriction: umbilical cord anomalies, fetal thrombotic vasculopathy, chronic villitis of unknown etiology and chronic histiocytic intervillositis. Some placental lesions have been reported associated with infants with neurologic impairment and can be as different as vascular lesions, villitis of unknown origin with stem villi vasculopathy, fetal thrombotic vasculopathy or umbilical cord anomalies. However, there is no direct link between a type of placental pathology and the infant's adverse outcome or his neurological risk. The maternal risk of recurrence is not easily predictable except for the chronic histiocytic intervillositis in which the estimated recurrence rate is very high. CONCLUSION: Placental morphological findings can play a critical role in explaining the IUGR. They always need to be correlated with clinical findings. PMID- 24210719 TI - [Delivery of the IUGR fetus]. AB - OBJECTIVE: The purpose of this paper is to review available data regarding the management of delivery in intra uterine growth retarded fetuses and try to get recommendations for clinical obstetrical practice. MATERIALS AND METHODS: Bibliographic research performed by consulting PubMed database and recommendations from scientific societies with the following words: small for gestational age, intra-uterine growth restriction, fetal growth restriction, very low birth weight infants, as well as mode of delivery, induction of labor, cesarean section and operative delivery. RESULTS: The diagnosis of severe IUGR justifies the orientation of the patient to a referral centre with all necessary resources for very low birth weight or premature infants Administration of corticosteroids for fetal maturation (before 34 WG) and a possible neuroprotective treatment by with magnesium sulphate (before 32-33 WG) should be discussed. Although elective caesarean section is common, there is no current evidence supporting the use of systematic cesarean section, especially when the woman is in labor. Induction of labor, even with unfavorable cervix is possible under continuous FHR monitoring, in favorable obstetric situations and in the absence of severe fetal hemodynamic disturbances. Instrumental delivery and routine episiotomy are not recommended. For caesarean section under spinal anesthesia, an adequate anesthetic management must ensure the maintenance of basal blood pressure. CONCLUSION: Compared with appropriate for gestational age fetus, IUGR fetus is at increased risk of metabolic acidosis or perinatal asphyxia during delivery. PMID- 24210720 TI - Free function muscle transfers for upper extremity reconstruction: a review of indications, techniques, and outcomes. AB - Free functional muscle transfer (FFMT) replaces destroyed, denervated, or resected skeletal muscle units in the upper extremity with functioning skeletal muscle from other locations in the body. Common indications for FFMT include brachial plexus injuries, ischemic contracture, tumor resection, and extensive direct muscle trauma. Recent studies have focused on improving patient outcomes through refinements in muscle flap harvest and inset, donor nerve selection, and postoperative management. In this review, we assess and summarize the current literature on FFMT, with emphasis on etiopathogenesis, diagnosis, treatment, postoperative management, and clinical outcomes. PMID- 24210721 TI - Prevention and treatment of elbow stiffness: a 5-year update. AB - Elbow stiffness is a challenging and common problem faced by upper extremity surgeons. Although functional improvements can be made with both nonsurgical and surgical management strategies, physicians must remain vigilant with efforts to prevent stiffness before it starts. Recent advancements in the biology and pathology of elbow contracture have led to improved understanding of this difficult problem, and they may lead to future breakthroughs in the prevention and treatment of elbow stiffness. This article serves as an update to our previous review of elbow stiffness, focusing on recent advancements in the past 5 years, as well as updating our current algorithm for treatment. PMID- 24210722 TI - Spindle cell carcinoma of the larynx presenting as a vocal fold cyst. AB - Spindle cell carcinoma (SPCC) is a rare, malignant variant of squamous cell carcinoma (SCC), which shows biphasic proliferation of the conventional SCC component and malignant spindle shape cells with sarcomatous appearance. We present two cases of SPCC of the true vocal fold that presented as a benign appearing subepithelial mass. We discuss the patient presentation, voice assessment, surgical treatment, and a review of the literature. PMID- 24210723 TI - [Middle-term results of a Silastic prosthesis used as a temporary spacer for unreconstructable radial head fractures]. AB - This study reports the use of silicone prosthesis as a temporary spacer for comminuted fracture of the radial head. Twelve men and eight women with a mean age of 42 years (17-54) were operated on in an average of five days following a comminuted fracture of the radial head. Silicone radial head prosthesis was implanted with a mean duration of eight months (3-18) between implantation and removal. At a mean period of five years after initial surgery, the mean DASH score was 40 (24-82), the mean MEPS score was 86 (60-100) giving ten excellent results, five good and five means. At the last clinical follow-up, the average flexion was 127 degrees (90-140) and 152 degrees (50-180) for pronation supination. Regarding our results, early removal of the Silastic implant prevented possible synovitis and failure of silicone implant. The stability of the elbow was obtained in all cases with association of a medial collateral ligament repair in case of instability. The use of a silicone radial head implant as a temporary spacer in case of radial head fracture type Mason III or IV seems to be a possible alternative to metal prostheses, whose implantation technique is demanding and sometimes not recommendable in young patients. PMID- 24210724 TI - Low uptake of upfront autologous transplantation for myeloma in a jurisdiction with universal health care coverage: a population-based patterns of care study in Australia. AB - BACKGROUND: Guidelines for the management of symptomatic multiple myeloma (MM) recommend upfront autologous stem cell transplantation (ASCT) for transplant eligible patients. PATIENTS AND METHODS: Using population-based data, we examined the characteristics of transplant-eligible patients who do not undergo upfront ASCT. Altogether, 686 newly diagnosed MM cases were identified through the population-based central cancer registry in Victoria, Australia from 2008 to 2009. We performed a detailed review of clinical notes and follow-up for at least 12 months after diagnosis for a subset of 225 patients who were aged < 70 years at diagnosis and had symptomatic MM. RESULTS: Of these 225 patients, 123 (55%) proceeded to receive upfront ASCT. Patient and disease factors associated with not receiving upfront ASCT were the presence of severe medical comorbidities, MM associated renal impairment, and initial referral to a medical oncologist rather than a hematologist. Place of residence (rural vs. metropolitan) was not significant. Of 121 patients aged < 65 years at diagnosis who had minor or no comorbidities, only 75 (62%) proceeded to upfront ASCT. CONCLUSION: A substantial percentage of apparently transplant-eligible patients with newly diagnosed MM do not proceed to upfront ASCT. Community practice appears to diverge from clinical guidelines. The reasons for this divergence require further study but reasons may include perceptions of toxicity vs. benefits of upfront ASCT. PMID- 24210725 TI - Life is lived forwards and understood backwards-experiences of being affected by acute coronary syndrome: commentary on Fors et al. (2013). PMID- 24210726 TI - A fortunate survival following a severe penetrating chest trauma. PMID- 24210727 TI - The effect of tai chi on chronic obstructive pulmonary disease: a pilot randomised study of lung function, exercise capacity and diaphragm strength. AB - BACKGROUND: Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease (COPD) have been widely reported, the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD. This study reported a randomised controlled trial, which investigated the effects of Tai Chi on lung function, exercise capacity, and diaphragm strength in patients with COPD. TRIAL DESIGN: Single blind randomised controlled study. SETTING: Department of Respiratory Medicine, Xiangya Hospital, Central South University. METHODS: Forty patients with COPD were randomised into either a control group or Tai Chi intervention group. Participants in the control group received only routine care, while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program. OUTCOMES: Lung function parameters, blood gas parameters, 6-min walking distance (6MWD), and diaphragm strength parameters. RESULTS: Lung function parameters (FEV1: 1.43 +/- 0.08 and FEV1 (%) predicted: 47.6 +/- 4.76), 6MWD (476 +/- 15) and diaphragm strength parameters (TwPes: 1.17 +/- 0.07, TwPga: -1.12 +/- 0.06, and TwPdi: 1.81 +/- 0.09) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care (p<0.05). These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline (p<0.05). In contrast, no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group (p>0.05). CONCLUSIONS: Tai Chi enhances lung function, exercise capacity, and diaphragm strength. However, this is only preliminary research data and a larger trial is needed for more detailed results. PMID- 24210728 TI - Amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion: complete mouth rehabilitation of a young adult. AB - Amelogenesis imperfecta is an autosomal dominant disorder. It is a group of hereditary diseases showing abnormal enamel density and crown malformation. This clinical report describes the oral rehabilitation of a young adult diagnosed with a variant of hypoplastic amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion. The treatment procedures of teeth extractions, endodontic treatment of remaining teeth followed by post and core restorations, esthetic and functional crown lengthening, and metal ceramic fixed dental prostheses were performed sequentially in the maxillary arch. The mandibular arch was restored with an overdenture. One-year follow-up revealed satisfactory results. PMID- 24210729 TI - Color match of machinable lithium disilicate ceramics: Effects of cement color and thickness. AB - STATEMENT OF PROBLEM: The effects of cement color and thickness on the color of machinable lithium disilicate (MLD) ceramic luted on metal foundation restorations is unknown. PURPOSE: The purpose of this study was to evaluate the effects of cement color and thickness on the shade matching of MLD restorations luted on silver-palladium (Ag-Pd) foundations. MATERIAL AND METHODS: Fifteen 1.5 mm-thick ceramic specimens were made from shade A1 LT lithium disilicate blocks. Five resin cements with different colors and opacities (Multilink Automix white opaque, Multilink Automix yellow, Nexus3 white opaque, Nexus3 white, Nexus3 yellow) of 3 thicknesses (300 MUm, 100 MUm, 50 MUm) were sequentially luted to a roughened Ag-Pd alloy foundation restoration block. Five shade measurements were made with a portable spectrophotometer after optically connecting the ceramic specimen to each cement foundation block. The color differences (DeltaE) between each specimen assembly and the target block (a 14*14*12-mm shade A1 LT crystalized e.max block) were recorded with the CIE (Commission internationale de l'eclairage) L*a*b* system. Clinical significance was determined by comparing color differences to perceptibility and acceptability thresholds with the 1 sample t test (alpha=.05). RESULTS: Both cement color and cement thickness significantly affected the mean values of the color difference (DeltaE) of lithium disilicate ceramic assemblies to the target block (P<.001). Among the 5 cements tested, the lowest mean DeltaE was observed for Nexus3 white opaque cement. Overall, the combination of Nexus3 white opaque cement and 100-MUm thickness led to the lowest mean DeltaE. The means of DeltaE were below the clinically perceptible level (DeltaE<2.6) for combinations of Nexus3 white opaque of 100-MUm and 300-MUm cement thicknesses (P<.001 and P=.022, respectively). The means of DeltaE were below the clinically acceptable level (DeltaE<5.5) for the following combinations: Nexus3 white opaque of 50-MUm thickness, Nexus3 white, and Nexus3 yellow for all tested cement thicknesses and Multilink white opaque or Multilink yellow of either 50-MUm or 100-MUm cement thickness (P<.001). The means of DeltaE were above the clinically acceptable level (DeltaE>5.5) for Multilink white opaque and Multilink yellow of 300-MUm cement thickness. CONCLUSIONS: The colors of machinable lithium disilicate ceramic restorations placed on Ag-Pd foundation were affected by both the color and thickness of cements. Among the 5 cements tested in this study, Nexus3 white opaque cement of 100 MUm or 300 MUm yielded shade matches below the clinical perceptible threshold (DeltaE<2.6) relative to the target block. PMID- 24210730 TI - Clinical performance and satisfaction of removable prostheses with self-adjusting magnetic attachments. AB - STATEMENT OF PROBLEM: Conventional magnetic attachments have rigid assemblies and are unable to compensate for the movement of the prosthesis under function, which may result in the deepening of periodontal pockets and an increase in the mobility of abutment teeth. PURPOSE: The purpose of this study was to evaluate the clinical performance and satisfaction of participants with removable prostheses with self-adjusting magnetic attachments that allow vertical and rotational movement. MATERIAL AND METHODS: The clinical performance of 17 prostheses with 22 self-adjusting magnetic attachments in 16 participants was analyzed for a mean of 3.1 years. Periodontal indices, including probing pocket depth and tooth mobility, were measured at denture placement (baseline) and from 0.5 to 5 years after insertion. Control data were obtained from the remaining teeth, which were restored by resin or metal coping. Prosthetic parameters, including the reduction of retention in self-adjusting magnetic attachments, reline, or fracture of dentures, were also recorded. A visual analog scale questionnaire on participant satisfaction with stability, comfort, and cleaning of the prostheses was completed. The Wilcoxon signed rank test and 1-way analysis of variance (alpha=.05) were performed on data collected at the time of prostheses placement and final follow-up evaluation. RESULTS: No significant differences were found in terms of probing pocket depth and tooth mobility between the baseline and postinsertion data for self-adjusting magnetic attachments and control teeth. Retention in all prostheses was stable, without reduction. Higher visual analog scale scores for "easy cleaning" were noted. CONCLUSIONS: No significant difference between baseline and postinsertion was noted regarding the periodontal condition of self-adjusting magnetic attachments and control teeth with resin or metal coping materials. PMID- 24210731 TI - A simplified technique for recording an implant-supported ovate pontic site in the esthetic zone. AB - Implant-supported fixed dental prostheses present an esthetic challenge, especially when an ovate pontic site has been progressively developed during the guided soft-tissue healing process with an interim restoration. This article describes a technique for an accurate capturing of the molded ovate pontic site of an implant-supported fixed dental prostheses and for transferring it to the definitive cast, which facilitates the dental ceramist's ability to design and fabricate an ovate pontic with adequate intaglio contours. PMID- 24210732 TI - Applicability and accuracy of an intraoral scanner for scanning multiple implants in edentulous mandibles: a pilot study. AB - STATEMENT OF PROBLEM: In the past 5 years, the use of intraoral digitizers has increased. However, data are lacking on the accuracy of scanning implant restorative platforms for prosthodontics with intraoral digitizers. PURPOSE: The purpose of this clinical pilot study was to assess the applicability and accuracy of intraoral scans by using abutments designed for scanning (scan abutments) in edentulous mandibles. MATERIAL AND METHODS: Twenty-five participants with complete mandibular overdentures retained by 2 implants and frameworks were included in this study. Scan abutments were placed on the implants intraorally and scanned with the iTero intraoral scanner. Also, scan abutments were placed on the implant analogs of the definitive casts and scanned with an extraoral laboratory scanner (Lava Scan ST scanner). Two 3-dimensional computer-aided design models of the scan abutments with predetermined center lines were subsequently imported and registered, together with each of the scanned equivalents. The distance between the centers of the top of the scan abutments and the angulations between the scan abutments was assessed. These values were compared with the measurements made on the 3-dimensional scans of the definitive casts, which were the participants' original definitive casts used for fabrication of soldered bars. The threshold for distance error was established to be 100 MUm. RESULTS: Four of the 25 intraoral scans were not suitable for research because the intraoral scanner was not able to stitch the separate scans together. Five of the 21 suitable scans demonstrated an interimplant distance error >100 MUm. Three of the 25 intraoral scans showed interimplant angulation errors >0.4 degrees. Only 1 scan showed both an acceptable interimplant distance (<100 MUm) and an acceptable angulation error (<0.4 degrees). CONCLUSIONS: Based on the intraoral scans obtained in this study, distance and angulation errors were too large to fabricate well-fitting frameworks on implants in edentulous mandibles. The main reason for the unreliable scans seemed to be the lack of anatomic landmarks for scanning. PMID- 24210733 TI - SIU/ICUD Consultation On Urethral Strictures: Epidemiology, etiology, anatomy, and nomenclature of urethral stenoses, strictures, and pelvic fracture urethral disruption injuries. AB - This committee reviewed and evaluated published data, and recommended standardized terminology relating to the epidemiology, etiology, anatomy, and nomenclature of urethral stenoses, urethral strictures, and pelvic fracture urethral disruption injuries, as well as their surgical management. A literature search using Medline, PubMed (U.S. National Library of Medicine and the National Institutes of Health), Embase, online acronym databases, and abstracts from scientific meetings was performed from 1980-2010. Articles were evaluated using the Levels of Evidence adapted by the International Consultation on Urological Diseases (ICUD) from the Oxford Centre for Evidence-Based Medicine. Recommendations were based on the level of evidence and discussed among the committee to reach a consensus. There is expert opinion to support standards regarding the epidemiology, anatomy, and nomenclature of urethral stenoses, urethral strictures, and pelvic fracture urethral disruption injuries. There is level 3 evidence regarding the epidemiology and etiology of urethral stenoses, urethral strictures, and pelvic fracture urethral injuries. The literature regarding the epidemiology, anatomy, and nomenclature of urethral stenoses, urethral strictures, and pelvic fracture urethral disruption injuries are sparse and generally of a low level of evidence. The proposed ICUD system does not readily apply to these areas. Further research is needed so that stronger levels of evidence can be developed leading to recommendations regarding the accuracy of the data. To improve future research and promote effective scientific progress and communication, a standardized nomenclature and anatomy regarding the urethra and urethral surgery is detailed herein. PMID- 24210734 TI - SIU/ICUD Consultation on Urethral Strictures: Pelvic fracture urethral injuries. AB - The posterior urethra pierces the perineal diaphragm in close relationship to the pubic arc elements of the bony pelvis to which it is tethered by attachments to the puboprostatic ligaments and the perineal membrane. Because of these relationships, it is not surprising that fracture disruptions of the pelvic ring can be associated with injuries to the urethra at this level. Although the relationship between pelvic fracture and posterior urethral injury has been recognized for >1 century, considerable controversy exists on almost any aspect of these injuries, from the anatomy and classification of the injuries to the strategies for acute management, reconstruction, and treatment of complications, to mention just a few. What it is not controversial and well known is that these injuries can result in significant morbidity in the long run--mainly strictures, erectile dysfunction, and urinary incontinence--which can cause lifelong disability. It also well known that, just as in many other areas of trauma, the severity and duration of the complications can be reduced considerably if the injury is diagnosed and treated promptly and efficiently. This chapter summarizes the most relevant published evidence about the management of pelvic fracture urethral injuries. This comprehensive review, performed by an international panel of experts, will provide valuable information and recommendations to help urologists worldwide improve the treatment and outcomes of their injured patients. PMID- 24210735 TI - Bridging efforts to longitudinally improve and evaluate VEnous thromboembolism prophylaxis uptake in hospitalized cancer patients through Interprofessional Teamwork (BELIEVE IT): a study by Princess Margaret Cancer Centre. AB - INTRODUCTION: Despite demonstrable risk of venous thromboembolism (VTE), thromboprophylaxis continues to be underutilized in hospitalized cancer patients. Our study evaluated institutional VTE prophylaxis rates after devising a series of strategic interventions to longitudinally improve adherence rates over a period of eight years. METHODS AND MATERIALS: Between 2004 and 2012, a series of interventions were implemented to improve the thromboprophylaxis rate among patients with solid tumours hospitalized at our institution using quality improvement methodology. Interventions included development of guidelines and institutional policies coupled with educational in-services for physicians, nurses and pharmacists and engagement of the Cancer Quality Committee. Thromboprophylaxis rates were monitored to assess response to interventions. RESULTS: At the outset in 2004, 11 of 57 (19.3%) eligible patients received appropriate pharmacological prophylaxis and formed the baseline of our analysis. Post-2009 policy implementation and educational sessions, 46.5% of an eligible 185 inpatients were administered thromboprophylaxis. Following a two-year grace period to allow for policy acceptance, three audits were conducted in 2011 for which an average prophylaxis rate of 62.3% resulted. In 2012, following another round of educational sessions, a 96.7% rate was achieved and maintained ten weeks later. Minimal bleeding risk was observed during this eight year initiative. CONCLUSION: A reproducible 96.7% prophylaxis uptake rate was the result of our perseverance and persistence in believing that culture change was inevitable through continuously collaborating with stakeholders at all levels. PMID- 24210736 TI - Risk reducing mastectomy, breast reconstruction and patient satisfaction in Norwegian BRCA1/2 mutation carriers. AB - The aim of this study was to evaluate the outcome of risk-reducing mastectomy in BRCA1/2 mutation carriers with and without breast cancer. Uptake, methods of operation and reconstruction, complications, patient satisfaction and histopathological findings were registered at all five departments of genetics in Norway. Data from 267 affected and unaffected BRCA1/2 mutation carriers were analyzed, including a study-specific questionnaire returned by 178 mutation carriers. There was a steady increase in the uptake of risk-reducing mastectomies during the study period. Complications were observed in 106/266 (39.7%) women. Patient satisfaction was high. The majority of women expressed great relief after risk-reducing mastectomy and would have chosen the same option again. PMID- 24210737 TI - [Frequency of fluoroquinolone resistance in Mycobacterium tuberculosis in Southeast Spain]. PMID- 24210738 TI - [Re-emergence of measles in the province of Guadalajara, Spain. Is it time to establish new strategies for its elimination?]. AB - BACKGROUND: Measles is a viral infection that was almost eradicated, but it is re emerging in Spain and Europe in recent years. The aim of this study was to describe the microbiological, clinical and epidemiological characteristics of a measles outbreak that occurred in Guadalajara (Spain) from June to August 2012. METHODS: A descriptive and retrospective study was conducted. A total of 117 samples (including serum, urine and pharyngeal swabs) from 52 patients were analyzed for measles. RESULTS: Measles was diagnosed in 50 patients, 41 of them by microbiological diagnosis, and 9 by epidemiological link. The patients were grouped in four community outbreaks. No imported cases were observed. Positive IgM and positive CRP were detected in 25 patients, positive CRP only in 11 and positive IgM only in 5. The genotype D4 was identified in 13 patients and the genotype A in a post-vaccine case. The age groups most affected were adults between 20-34 years of age (38%) and younger than 15 months (26%). The large majority (86%) of patients were unvaccinated (44% Roma population, 27% younger than 15 months, 11% ideological reasons), 6% had one vaccine dose. The signs/symptoms were: rash and fever, 100%, cough, 82%, and conjunctivitis 50%. Almost one-third (32%) of patients were hospitalized, and 28% had complications. CONCLUSIONS: It is very important to intensify the epidemiological surveillance of infections in the elimination phase. The increased incidence of measles was associated to unvaccinated pockets, presenting a challenge for Public Health Centers. These agencies should prepare strategies to obtain a higher vaccine coverage for the eradication of measles. PMID- 24210739 TI - Tracing the primordial Chlamydiae: extinct parasites of plants? AB - Chlamydiae are obligate intracellular bacteria found as symbionts and pathogens in a wide range of eukaryotes, including protists, invertebrates, and vertebrates. It was recently proposed that an ancient chlamydial symbiont facilitated the establishment of primary plastids in a tripartite symbiosis with cyanobacteria and early eukaryotes. In this review, we summarize recent advances in understanding of the lifestyle and the evolutionary history of extant Chlamydiae. We reconstruct and describe key features of the ancient chlamydial symbiont. We propose that it was already adapted to an intracellular lifestyle before the emergence of Archaeplastida, and that several observations are compatible with an essential contribution of Chlamydiae to the evolution of algae and plants. PMID- 24210740 TI - Perceived coercion in voluntary hospital admission. AB - The legal status of service users admitted to psychiatric wards is not synonymous with the level of coercion that they can perceive during the admission. This study aimed to identify and describe the proportion of individuals who were admitted voluntarily but experienced levels of perceived coercion comparable to those admitted involuntarily. Individuals admitted voluntarily and involuntarily to three psychiatric hospitals were interviewed using the MacArthur Admission Experience Interview and the Structured Clinical Interview for DSM-IV diagnoses. One hundered sixty-one individuals were interviewed and 22% of the voluntarily admitted service users had levels of perceived coercion similar to that of the majority of involuntarily admitted service users. Voluntarily admitted service users who experienced high levels of perceived coercion were more likely to have more severe psychotic symptoms, have experienced more negative pressures and less procedural justices on admission. Individuals brought to hospital under mental health legislation but who subsequently agreed to be admitted voluntarily and those treated on a secure ward also reported higher levels of perceived coercion. It needs to be ensured that if any service user, whether voluntary or involuntary, experiences treatment pressures or coercion that there is sufficient oversight of the practice, to ensure that individual's rights are respected. PMID- 24210741 TI - Nocebo in clinical trials for depression: a meta-analysis. AB - Nocebo refers to adverse events (AEs) related to negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo controlled randomized clinical trials (RCTs). We sought to examine the AEs following placebo administration in RCTs for depression (D). After a systematic Medline search for RCTs in depression published in the last decade we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. Data were extracted from 21 RCTs fulfilling search criteria. Of 3255 placebo-treated patients, 44.7% (95% CI: 22.3-68.3%) reported at least one AE, and 4.5% (95% CI: 3.4-5.8%) discontinued placebo treatment due to intolerance. AE rates in placebo and active drug treated patients were correlated quantitatively (r=0.915, p<0.001) and qualitatively, but not dropout rates (r=0.047). We conclude that almost one out of 20 placebo treated patients discontinued treatment due to AEs, indicating a significant nocebo in trials for depression treatment adversely affecting adherence and efficacy of current treatments in clinical practice, with additional implications for trial designing. PMID- 24210742 TI - Association between the polymorphisms of the selected genes encoding dopaminergic system with ADHD and autism. PMID- 24210743 TI - Distress in primary caregivers and patients listed for liver transplantation. AB - Orthotopic liver transplantation (LTx) has become a routine procedure in the treatment of end-stage liver disease. During the waiting period for transplantation, the patient's family members are also highly affected. We examined the course of distress and quality of life (QOL) in 47 patients awaiting LTx and distress in 24 caregivers at baseline and in intervals of 4-6 weeks, using The Hospital Anxiety and Depression Scale (HADS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). All subscales of the EORTC QLQ-C30, except emotional functioning, were lower than normal at baseline. Little change in patients' QOL was observed during the waiting period. In the HADS, there were significantly higher anxiety scores in caregivers than in patients both at baseline and after 1 2 months and the third assessment, with the difference after 3-5 months reaching almost significance. Caregivers' anxiety levels increased significantly. Relatives showed more depression than patients only at month 1-2 and a significant increase in depression from baseline to month 1-2. In patients, depression scores remained relatively stable throughout all visits. Our results emphasize the importance of evaluation of psychic stress especially in relatives during the waiting period for LTx. PMID- 24210744 TI - Quality of life instruments used in mental health research: properties and utilization. AB - Quality of life (QoL) assessment is increasingly used in mental health. Multiple instruments exist, but the conditions for choosing one instrument over another for purposes of a specific study are not clear. We performed a systematic review to identify the QoL instruments used in mental health. The instruments were systematically described regarding their intrinsic properties (e.g., generic v. disease-specific) and their characteristics of utilization in studies (e.g., study objectives). Using cluster analyses, we investigated the existence of similar instruments with respect to each of these sets of characteristics and studied potential links between instruments' intrinsic properties and their characteristics of utilization. We included 149 studies in which 56 distinct instruments were used. Similarities were found among instruments in terms of their intrinsic properties as well as their characteristics of utilization, leading to the construction of four clusters of instruments in each case. However, no relevant links were identified between instruments' intrinsic properties and their characteristics of utilization, suggesting that the choice of QoL instruments did not depend on their properties. A consensus about common QoL instruments must be reached to facilitate the choice of instruments, the comparison of results and thus to have an impact on clinical and policy decision making. PMID- 24210745 TI - Influence of violent video gaming on determinants of the acquired capability for suicide. AB - The interpersonal theory of suicidal behavior proposes that fearlessness of death and physical pain insensitivity is a necessary requisite for self-inflicted lethal self-harm. Repeated experiences with painful and provocative events are supposed to cause an incremental increase in acquired capability. The present study examined whether playing a first-person shooter-game in contrast to a first person racing game increases pain tolerance, a dimension of the acquired capability construct, and risk-taking behavior, a risk factor for developing acquired capability. N=81 male participants were randomly assigned to either play an action-shooter or a racing game before engaging in a game on risk-taking behavior and performing a cold pressor task (CPT). Participants exhibited higher pain tolerance after playing an action shooter game than after playing a racing game. Furthermore, playing an action shooter was generally associated with heightened risk-taking behavior. Group-differences were not attributable to the effects of the different types of games on self-reported mood and arousal. Overall these results indicate that action-shooter gaming alters pain tolerance and risk-taking behavior. Therefore, it may well be that long-term consumption of violent video games increases a person's capability to enact lethal self-harm. PMID- 24210746 TI - Transarterial endovascular treatment in the management of life-threatening carotid blowout syndrome in head and neck cancer patients: review of the literature. AB - OBJECTIVES: Carotid blowout syndrome is a rare but devastating complication in patients with head and neck malignancy, and is associated with high morbidity and mortality. Bleeding from the carotid artery or its branches is a well-recognized complication following treatment or recurrence of head and neck cancer. It is an emergency situation, and the classical approach to save the patient's life is to ligate the carotid artery. But the surgical treatment is often technically difficult. Endovascular therapies were recently reported as good alternatives to surgical ligation. METHODS: Retrospective review of three cases of acute or threatened carotid hemorrhage managed by endovascular therapies. RESULTS: Two patients presented with acute carotid blowout, and one patient with a sentinel bleed. Two patients had previously been treated with surgery and chemo radiation. One patient was treated by chemo radiation. Two had developed pharyngocutaneous fistulas, and one had an open necrosis filled wound that surrounded the carotid artery. In two patients, stent placement resolved the acute hemorrhage. In one patient, superselective embolization was done. Mean duration follow-up was 10.2 months. No patient had residual sequelae of stenting or embolization. CONCLUSION: Management of carotid blow syndrome is very critical and difficult. A multidisciplinary approach is very important in the management of carotid blow syndrome. Correct and suitable management can be life saving. An endovascular technique is a good and effective alternative with much lower morbidity rates than surgical repair or ligation. PMID- 24210747 TI - [Acute rupture of an abdominal aortic aneurysm revealing Takayasu arteritis]. AB - Arterial aneurysms are most commonly (60% of cases) located in the infrarenal abdominal aorta. An inflammatory mechanism is involved in only 10% of cases. Infrarenal abdominal aortic aneurysms revealing Takayasu's disease is unusual. Takayasu's disease is a rare vasculitis affecting large arteries in young people. It is 10 times more common in women. We report the case of an acute rupture of an abdominal aortic aneurysm revealing Takayasu arteritis in a 39-year-old man with an uneventful medical history. PMID- 24210748 TI - [Contrast enhanced ultrasound can show symptomatic carotid lesions not visualized with magnetic resonance angiography]. AB - We report the cases of two patients who presented symptoms focused on a wall of the common carotid: carotidodynia in one patient and a transient ischemic attack in the other. The B-mode ultrasound showed an enlarged thickened medio adventitial echostructure with a slightly heterogeneous and iso or hypoechoic appearance. There was no narrowing. Injection of ultrasound contrast led to significant enhancement in the wall reflecting neovascularization secondary to inflammation. Other imaging methods (MR and CT angiography) found no abnormality. At the 3-month follow-up visit, the surface area of the lesions was greatly decreased and the ultrasound contrast enhancement had disappeared. These two cases illustrate how focal lesions of the carotid wall missed on MR and CT angiography can be detected and visualized with B-mode ultrasound contrast enhancement. Contrast enhanced ultrasound leads to the concept of "active lesions" resulting from inflammatory processes that can be readily monitored without radiation. PMID- 24210749 TI - [Secretan's syndrome: myth or pathomimia?]. AB - Secretan's syndrome is a rare condition involving generally trauma-induced hard edema of the dorsal aspect of the hand. The cause is poorly understood but factitious trauma is often suspected. CASE REPORT: A 42-year-old woman presented with a fortuitous edema on the back of the right hand. The minimally depressible edema was associated with moderately intense mechanical pain. Routine laboratory tests were normal. An extensive imaging work-up (bone x-ray of the hand and wrist, bone scintigraphy, computed tomography phlebography, lymphoscintigraphy, magnetic resonance imaging) was equally non-contributive. The diagnosis of self inflected trauma was suggested by the atypical nature of the edema, the absence of any organic disorder on the tests performed, and the patient's attitude concerning her disease. In this clinical context, the diagnosis of Secretan's syndrome was retained. Outcome was compatible, with secondary development of complex regional pain syndrome. DISCUSSION: Three forms of Secretan's syndrome have been recently described: benign; hyperplastic; and mixed. The cause remains poorly defined. Certain authors report that it is most likely related to pathomimia. Treatment can combine physiotherapy and psychological counseling. CONCLUSION: Secretan's syndrome is a poorly-understood and rarely-described condition that may be underdiagnosed. Physicians specialized in vascular medicine should be aware of this syndrome and its difficult diagnosis by elimination. PMID- 24210750 TI - [Posterior cerebral artery infarctions with possible interaction between hypoperfusion and embolism]. AB - Although embolism and hypoperfusion may well occur concurrently in a non negligible proportion of cerebral infarction patients, there is currently lack of proof, especially in the posterior circulation. Here, we are reporting on a case of multiple cerebral infarctions in a patient with neurofibromatosis type 1, multiple vascular abnormalities of the posterior cerebral circulation and intracranial artery occlusion. We hypothesize that cerebral blood flow impairment may have affected the clearance and destination of embolic particles. PMID- 24210754 TI - Do we need a radiology zoo? PMID- 24210756 TI - The role of a sodium ion binding site in the allosteric modulation of the A(2A) adenosine G protein-coupled receptor. AB - The function of G protein-coupled receptors (GPCRs) can be modulated by a number of endogenous allosteric molecules. In this study, we used molecular dynamics, radioligand binding, and thermostability experiments to elucidate the role of the recently discovered sodium ion binding site in the allosteric modulation of the human A(2A) adenosine receptor, conserved among class A GPCRs. While the binding of antagonists and sodium ions to the receptor was noncompetitive in nature, the binding of agonists and sodium ions appears to require mutually exclusive conformational states of the receptor. Amiloride analogs can also bind to the sodium binding pocket, showing distinct patterns of agonist and antagonist modulation. These findings suggest that physiological concentrations of sodium ions affect functionally relevant conformational states of GPCRs and can help to design novel synthetic allosteric modulators or bitopic ligands exploiting the sodium ion binding pocket. PMID- 24210757 TI - Mycobacterium tuberculosis dihydrofolate reductase reveals two conformational states and a possible low affinity mechanism to antifolate drugs. AB - Inhibition of the biosynthesis of tetrahydrofolate (THF) has long been a focus in the treatment of both cancer and infectious diseases. Dihydrofolate reductase (DHFR), which catalyzes the last step, is one of the most thoroughly explored targets of this pathway, but there are no DHFR inhibitors used for tuberculosis treatment. Here, we report a structural, site-directed mutagenesis and calorimetric analysis of Mycobacterium tuberculosis DHFR (MtDHFR) in complex with classical DHFR inhibitors. Our study provides insights into the weak inhibition of MtDHFR by trimethoprim and other antifolate drugs, such as pyrimethamine and cycloguanil. The construction of the mutant Y100F, together with calorimetric studies, gives insights into low affinity of MtDHFR for classical DHFR inhibitors. Finally, the structures of MtDHFR in complex with pyrimethamine and cycloguanil define important interactions in the active site and provide clues to the more effective design of antibiotics targeted against MtDHFR. PMID- 24210755 TI - ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients. AB - PURPOSE: Operable thoracic esophageal/gastroesophageal junction carcinoma (EC) is often treated with chemoradiation and surgery but tumor responses are unpredictable and heterogeneous. We hypothesized that aldehyde dehydrogenase-1 (ALDH-1) could be associated with response. METHODS: The labeling indices (LIs) of ALDH-1 by immunohistochemistry in untreated tumor specimens were established in EC patients who had chemoradiation and surgery. Univariate logistic regression and 3-fold cross validation were carried out for the training (67% of patients) and validation (33%) sets. Non-clinical experiments in EC cells were performed to generate complimentary data. RESULTS: Of 167 EC patients analyzed, 40 (24%) had a pathologic complete response (pathCR) and 27 (16%) had an extremely resistant (exCRTR) cancer. The median ALDH-1 LI was 0.2 (range, 0.01-0.85). There was a significant association between pathCR and low ALDH-1 LI (p <= 0.001; odds-ratio [OR] = 0.432). The 3-fold cross validation led to a concordance index (C-index) of 0.798 for the fitted model. There was a significant association between exCRTR and high ALDH-1 LI (p <= 0.001; OR = 3.782). The 3-fold cross validation led to the C-index of 0.960 for the fitted model. In several cell lines, higher ALDH-1 LIs correlated with resistant/aggressive phenotype. Cells with induced chemotherapy resistance upregulated ALDH-1 and resistance conferring genes (SOX9 and YAP1). Sorted ALDH-1+ cells were more resistant and had an aggressive phenotype in tumor spheres than ALDH-1- cells. CONCLUSIONS: Our clinical and non clinical data demonstrate that ALDH-1 LIs are predictive of response to therapy and further research could lead to individualized therapeutic strategies and novel therapeutic targets for EC patients. PMID- 24210758 TI - Stereochemical preferences modulate affinity and selectivity among five PDZ domains that bind CFTR: comparative structural and sequence analyses. AB - PDZ domain interactions are involved in signaling and trafficking pathways that coordinate crucial cellular processes. Alignment-based PDZ binding motifs identify the few most favorable residues at certain positions along the peptide backbone. However, sequences that bind the CAL (CFTR-associated ligand) PDZ domain reveal only a degenerate motif that overpredicts the true number of high affinity interactors. Here, we combine extended peptide-array motif analysis with biochemical techniques to show that non-motif "modulator" residues influence CAL binding. The crystallographic structures of 13 CAL:peptide complexes reveal defined, but accommodating stereochemical environments at non-motif positions, which are reflected in modulator preferences uncovered by multisequence substitutional arrays. These preferences facilitate the identification of high affinity CAL binding sequences and differentially affect CAL and NHERF PDZ binding. As a result, they also help determine the specificity of a PDZ domain network that regulates the trafficking of CFTR at the apical membrane. PMID- 24210760 TI - Dorsal scapholunate stabilization using Viegas' capsulodesis: 25 cases with 26 months-follow-up. AB - Intercarpal instability is often secondary to a scapholunate interosseous (SLIO) ligament lesion. Its reconstruction is thus essential. Classical capsulodesis techniques fix the scaphoid in extension and do not reproduce the physiologic ligamentous isometry of the wrist. The authors use the technique of Viegas, which seems to respect this isometry: the dorsal intercarpal ligament is re-inserted dorsally to reattach the capsule on the dorsal SLIO and to reinforce it. Between 2006 and 2010, 25 wrists were operated on in 12 men and 12 women of mean age 38 years. All patients presented with pain often associated with loss of power, decreased mobility or a debilitating click. The mean follow-up was 26 months. Postoperative and preoperative data were compared. Flexion/extension range increased by 2.6 degrees , radioulnar deviation increased by 21.1 degrees . Grip strength increased by 8.7 kgf. Pain decreased by 3 points on the VAS and the PRWE improved by 59 points. We observed four CRPS, one EPL lesion and one case of superficial track pin infection. We got eleven excellent results, nine good, two moderate and three bad, two of which were re-operated. Viegas' capsulodesis does not present major technical difficulty. The results show no stiffness in flexion/extension. There was evident improvement in radioulnar deviation, grip strength, pain and PRWE scores. This technique provides effective treatment for a difficult or irreparable lesion of the SLIO ligament, without fixed carpal instability corresponding to Geissler arthroscopic stages 2 to 4 and Garcia-Elias stages 3 and 4. The capsulodesis produces an effective stabilization without stiffness. Precautions should be undertaken to avoid CRPS and pin complications. PMID- 24210761 TI - New editor--new enforcement of ethical standards? PMID- 24210759 TI - Structural interactions between inhibitor and substrate docking sites give insight into mechanisms of human PS1 complexes. AB - Presenilin-mediated endoproteolysis of transmembrane proteins plays a key role in physiological signaling and in the pathogenesis of Alzheimer disease and some cancers. Numerous inhibitors have been found via library screens, but their structural mechanisms remain unknown. We used several biophysical techniques to investigate the structure of human presenilin complexes and the effects of peptidomimetic gamma-secretase inhibitors. The complexes are bilobed. The head contains nicastrin ectodomain. The membrane-embedded base has a central channel and a lateral cleft, which may represent the initial substrate docking site. Inhibitor binding induces widespread structural changes, including rotation of the head and closure of the lateral cleft. These changes block substrate access to the catalytic pocket and inhibit the enzyme. Intriguingly, peptide substrate docking has reciprocal effects on the inhibitor binding site. Similar reciprocal shifts may underlie the mechanisms of other inhibitors and of the "lateral gate" through which substrates access to the catalytic site. PMID- 24210762 TI - Catastrophic healthcare expenditure - drivers and protection: the Portuguese case. AB - The objective of this paper is to assess the extent of catastrophic healthcare expenditure, which can lead to impoverishment, even in a country with a National Health Service, such as Portugal. The level of catastrophic healthcare expenditure will be identified before the determinants of these catastrophic payments are analyzed. Afterwards, the effects of existing exemptions to copayments in health care use will be tested and the relationship between catastrophe and impoverishment will be discussed. Catastrophe is calculated from the Portuguese Household Budget Surveys of 2000 and 2005, and then analyzed using logistic regression models. The results show that catastrophe due to healthcare out-of-pocket payments are a sizeable issue in Portugal. Exemptions from out-of pocket expenses for medical care should be created to prevent vulnerable groups from facing catastrophic healthcare spending. These vulnerable groups include children, people with disabilities and individuals suffering from chronic conditions. Disability proxies offer straightforward policy options for an exemption for the elderly with recognized disabilities. An exemption of retired people with disabilities is therefore recommended to policymakers as it targets a vulnerable group with high risk of facing catastrophic healthcare expenditure. PMID- 24210763 TI - Risk selection and cost shifting in a prospective physician payment system: evidence from Ontario. AB - We study the risk-selection and cost-shifting behavior of physicians in a unique capitation payment model in Ontario, using the incentive to enroll and care for complex and vulnerable patients as a case study. This incentive, which is incremental to the regular capitation payment, ceases after the first year of patient enrollment and may therefore impact on the physician's decision to continue to enroll the patient. Furthermore, because the enrolled patients in Ontario can seek care from any provider, the enrolling physician may shift some treatment costs to other providers. Using longitudinal administrative data and a control group of physicians in the fee-for-service model who were eligible for the same incentive, we find no evidence of either patient 'dumping' or cost shifting. These results highlight the need to re-examine the conventional wisdom about risk selection for physician payment models that significantly deviate from the stylized capitation model. PMID- 24210764 TI - Impact of crystalline lens opacification on effective phacoemulsification time in femtosecond laser-assisted cataract surgery. AB - PURPOSE: To compare effective phacoemulsification time in cataract surgery performed by manual phacoemulsification vs femtosecond laser-assisted lens fragmentation. DESIGN: Retrospective, consecutive, nonrandomized, comparative case series. METHODS: The setting was the Department of Ophthalmology, Goethe University, Frankfurt, Germany. The study population included 150 eyes of 86 patients with senile cataract. In the intervention, 88 eyes (group 1) underwent femtosecond laser-assisted surgery (corneal incisions, capsulotomy, lens fragmentation) using the LenSx platform (Alcon) and residual lens work-up with pulsed ultrasound energy (Infiniti Vision System; Alcon). In 62 eyes (group 2), complete cataract removal was performed with phacoemulsification only, using pulsed ultrasound energy with the same device (Infiniti). Nucleus staging (Pentacam nucleus staging; PNS) was evaluated using Pentacam HR (Oculus); endothelial cell density was measured using specular microscopy (NonCon Robo). The main outcome measures were as follows. Mean preoperative PNS staging was assessed using an automatic ordinal scaling (PNS-O, grades 0-5) and a manually defined density grid derived from Scheimpflug imaging (PNS-P [%]). Effective phacoemulsification time and endothelial cell loss were evaluated in both groups. RESULTS: Preoperative PNS-O and PNS-P showed no significant difference between groups (P = 0.267). Overall mean effective phacoemulsification time was significantly lower in group 1 (1.58 +/- 1.02 seconds) compared to 4.17 +/- 2.06 seconds in group 2 (P = 0.001). Effective phacoemulsification time was significantly lower in group 1 for all PNS-O stages (P < 0.001). With increasing preoperative PNS-P, effective phacoemulsification time increased in both groups; however, this gain was noticeably, but not significantly, lower in group 2. Endothelial cell loss was significantly lower in group 1 (P = 0.02). CONCLUSIONS: Femtosecond laser-assisted cataract surgery allows a significant reduction in effective phacoemulsification time, which correlates positively with the preoperative lens opacity. PMID- 24210765 TI - Randomized, prospective, comparative trial of EX-PRESS glaucoma filtration device versus trabeculectomy (XVT study). AB - PURPOSE: To compare the clinical outcomes of the EX-PRESS glaucoma filtration device placed under a partial-thickness scleral flap with trabeculectomy. DESIGN: Randomized, prospective, multicenter trial. METHODS: A total of 120 eyes in 120 subjects were analyzed, including 59 eyes treated with EX-PRESS and 61 eyes treated with trabeculectomy. Both the EX-PRESS and the trabeculectomy groups were treated intraoperatively with mitomycin C and followed postoperatively for 2 years. Surgical success was defined as 5 mm Hg <= intraocular pressure <= 18 mm Hg, with or without medications, without further glaucoma surgery. RESULTS: Mean intraocular pressure was significantly reduced compared with baseline in both groups (P < 0.001). Average intraocular pressure and number of medications were similar in both groups during follow-up, with mean intraocular pressure at 2 years after surgery of 14.7 +/- 4.6 mm Hg and 14.6 +/- 7.1 mm Hg in the EX-PRESS and trabeculectomy groups, respectively (P = 0.927). At 2 years after surgery, the success rate was 83% and 79% in the EX-PRESS and trabeculectomy groups, respectively (P = 0.563). Although visual acuity (logMAR) was significantly decreased on day 1 in both groups, the vision was not significantly different compared with baseline at 1 month after EX-PRESS implant (P = 0.285) and 3 months after trabeculectomy (P = 0.255). The variance of early postoperative intraocular pressure values was similar between groups on the first postoperative day but higher after trabeculectomy compared with EX-PRESS implant on day 7 (P = 0.003). The total number of postoperative complications was higher after trabeculectomy than after EX-PRESS implantation (P = 0.013). CONCLUSIONS: Mean intraocular pressures, medication use, and surgical success were similar at 2 years after treatment with the EX-PRESS device and trabeculectomy. Vision recovery between groups was also similar throughout the study, although return to baseline vision was more rapid in the EX-PRESS group. Intraocular pressure variation was lower during the early postoperative period, and postoperative complications were less common after EX-PRESS implantation compared with trabeculectomy. PMID- 24210766 TI - Clinical outcomes in descemet stripping automated endothelial keratoplasty with internationally shipped precut donor corneas. AB - PURPOSE: To report the endothelial cell loss and clinical outcomes in Descemet stripping automated endothelial keratoplasty (DSAEK) with internationally shipped, precut donor corneas. DESIGN: Retrospective analysis of a noncomparative case series. METHODS: The setting was a single hospital. The clinical results of 134 eyes of 128 patients who underwent DSAEK in Kyoto, Japan, with internationally shipped precut donor corneas from Portland, Oregon, or Seattle, Washington, were evaluated. In addition, 40 precut donor corneas from Seattle were evaluated in respect to the postprecut international shipment-related loss of corneal endothelial cell density (ECD). Observation procedures were noncontact specular microscopy. The main outcome measures were the evaluation of international shipment-related ECD loss, postoperative ECD, visual recovery, and complications. RESULTS: The mean postprecut ECD loss in 40 donor corneas during international shipment was 2.3%. The mean elapsed time from cut to surgery was 63.2 +/- 31.1 hours. At 6, 12, 24, and 36 months postoperatively, the mean ECD of the internationally shipped donor corneas was 2038, 1933, 1670, and 1431 cells/mm(2), respectively. The mean ECD loss at 6, 12, 24, 36 months after DSAEK was 30%, 34%, 44%, and 51%, respectively. Preoperative logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity was 1.40 +/- 0.55, and at 12 months after DSAEK was 0.22 +/- 0.19. Complications included graft dislocation in 12 eyes (8.9%) and graft rejection in 3 eyes (2.2%). CONCLUSIONS: The present study shows that the outcomes of DSAEK with internationally shipped precut donor corneas were acceptable and that the additional endothelial cell loss associated with international shipment was minimal and did not affect the clinical results. PMID- 24210767 TI - Ophthalmic randomized controlled trials reports: the statement of the hypothesis. AB - PURPOSE: To evaluate whether the ophthalmic randomized controlled trials (RCTs) were designed properly, their hypotheses stated clearly, and their conclusions drawn correctly. DESIGN: A systematic review of 206 ophthalmic RCTs. METHODS: The objective statement, methods, and results sections and the conclusions of RCTs published in 4 major general clinical ophthalmology journals from 2009 through 2011 were assessed. The clinical objective and specific hypothesis were the main outcome measures. RESULTS: The clinical objective of the trial was presented in 199 (96.6%) studies and the hypothesis was specified explicitly in 56 (27.2%) studies. One hundred ninety (92.2%) studies tested superiority. Among them, 17 (8.3%) studies comparing 2 or more active treatments concluded equal or similar effectiveness between the 2 arms after obtaining insignificant results. There were 5 noninferiority studies and 4 equivalence studies. How the treatments were compared was not mentioned in 1 of the noninferiority studies. Two of the equivalence studies did not specify the equivalence margin and used tests for detecting difference rather than confirming equivalence. CONCLUSIONS: The clinical objective commonly was stated, but the prospectively defined hypothesis tended to be understated in ophthalmic RCTs. Superiority was the most common type of comparison. Conclusions made in some of them with negative results were not consistent with the hypothesis, indicating that noninferiority or equivalence may be a more appropriate design. Flaws were common in the noninferiority and equivalence studies. Future ophthalmic researchers should choose the type of comparison carefully, specify the hypothesis clearly, and draw conclusions that are consistent with the hypothesis. PMID- 24210768 TI - Development of a score and probability estimate for detecting angle closure based on anterior segment optical coherence tomography. AB - PURPOSE: To develop a score along with an estimated probability of disease for detecting angle closure based on anterior segment optical coherence tomography (AS OCT) imaging. DESIGN: Cross-sectional study. METHODS: A total of 2047 subjects 50 years of age and older were recruited from a community polyclinic in Singapore. All subjects underwent standardized ocular examination including gonioscopy and imaging by AS OCT (Carl Zeiss Meditec). Customized software (Zhongshan Angle Assessment Program) was used to measure AS OCT parameters. Complete data were available for 1368 subjects. Data from the right eyes were used for analysis. A stepwise logistic regression model with Akaike information criterion was used to generate a score that then was converted to an estimated probability of the presence of gonioscopic angle closure, defined as the inability to visualize the posterior trabecular meshwork for at least 180 degrees on nonindentation gonioscopy. RESULTS: Of the 1368 subjects, 295 (21.6%) had gonioscopic angle closure. The angle closure score was calculated from the shifted linear combination of the AS OCT parameters. The score can be converted to an estimated probability of having angle closure using the relationship: estimated probability = e(score)/(1 + e(score)), where e is the natural exponential. The score performed well in a second independent sample of 178 angle closure subjects and 301 normal controls, with an area under the receiver operating characteristic curve of 0.94. CONCLUSIONS: A score derived from a single AS OCT image, coupled with an estimated probability, provides an objective platform for detection of angle closure. PMID- 24210769 TI - Post-weaning cranial ontogeny in two bandicoots (Mammalia, Peramelomorphia, Peramelidae) and comparison with carnivorous marsupials. AB - The ontogeny of the skull has been studied in several marsupial groups such as didelphids, microbiotheriids, and dasyurids. Here, we describe and compare the post-weaning ontogeny of the skull in two species of bandicoots, Echymipera kalubu (Echymiperinae) and Isoodon macrourus (Peramelinae), analyzing specific allometric trends in both groups, describing common (and specific) patterns, and discussing them on functional and phylogenetic grounds. Growth patterns were analyzed both qualitatively and quantitatively, including bivariate and multivariate analyses of allometry. We also evaluated character transformation and phylogenetic signals of the allometric patterns in several groups of marsupials and some placentals. We identified morphological changes between juvenile and adult stages in both species of peramelids, many related to the development of the trophic apparatus. Notable differences were detected in the patterns of growth, suggesting divergences in ontogenetic trajectories between both species. Both bivariate and multivariate methods indicate that positive allometries in E. kalubu apply to longitudinal dimensions, whereas in I. macrourus, positive allometries are restricted to vertical dimensions of the skull. The comparison of the allometric trends of two bandicoots with previously studied taxa reveals that although peramelids exhibit a particularly short gestation period and divergent morphology compared to other marsupials, their pattern does not show any particular trend. Some allometric trends seem to be highly conserved among the species studied, showing weak phylogenetic signal. Marsupials in general do not show particular patterns of post-weaning skull growth compared with placentals. PMID- 24210770 TI - An examination of associations between social norms and risky alcohol use among African American men who have sex with men. AB - BACKGROUND: Research has indicated associations between risky alcohol consumption and sexual risk behavior, which may in turn present risk of HIV acquisition or transmission. Little is known about social determinants of problematic alcohol use among African American MSM (AA MSM), a risk group disproportionately affected by HIV. The present study sought to explore associations between risky alcohol use and perceived peer norms of alcohol use among a sample of urban African American men who have sex with men (AA MSM). METHODS: A cross-sectional survey was administered to 142 AA MSM in Baltimore, Maryland, recruited using active and passive methods. Risky and hazardous alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) and participants self-reported descriptive and injunctive peer norms regarding frequency and quantity of alcohol consumption. RESULTS: Nearly half reported hazardous or high risk consumption of alcohol. Perceived peer alcohol norms, both descriptive and injunctive, were associated with alcohol use, including hazardous use. CONCLUSIONS: The findings highlight the role of social factors on problematic alcohol use among AA MSM. Results indicate that AA MSM's use of alcohol is associated with their perceptions of peer alcohol use. Potential interventions could include norms based campaigns that seek to reduce risky alcohol consumption among AA MSM as well as programs to screen and identify individuals with problematic alcohol use. PMID- 24210771 TI - Alcohol and substance screening and brief intervention for detainees kept in police custody. A feasibility study. AB - BACKGROUND: Screening and brief intervention programs related to addictive disorders have proven effective in a variety of environments. Both the feasibility and outcome of brief interventions performed in police custody by forensic physicians are unknown. Our objectives were to characterize addictive behaviors in detainees and to evaluate the feasibility of a brief intervention at the time of the medical examination in police custody. METHODS: This prospective study included 1000 detainees in police custody who were examined by a physician for the assessment of fitness for detention. We used a standardized questionnaire and collected data concerning individual characteristics, addictive disorders, and reported assaults or observed injuries. RESULTS: 944 men and 56 women (94-6%) were studied. We found an addictive disorder in 708 of 1000 cases (71%), with the use of tobacco (62%), alcohol (36%), cannabis (35%), opiates (5%), and cocaine (4%) being the most common. A brief intervention was performed in 544 of these 708 cases (77%). A total of 139 of the 708 individuals (20%) expressed a willingness to change and 14 of 708 (2%) requested some information on treatment options. The main reasons why brief interventions were not performed were aggressive behaviors, drowsiness, or fanciful statements by the detainee. CONCLUSION: Brief interventions and screening for addictive behaviors in police custody are feasible in the majority of cases. The frequent link between addictive behaviors and the suspected crimes highlights the value of such interventions, which could be incorporated into the public health mission of the physician in police custody. PMID- 24210773 TI - Effectiveness of CT-guided sclerotherapy with estimated ethanol concentration for treatment of symptomatic simple hepatic cysts. AB - BACKGROUND AND OBJECTIVE: The mean Hounsfield value of 99.9% ethanol did get down to -190 Hounsfield units (HU), there was a linear correlation between ethanol concentration and Hounsfield values. We aimed to evaluate whether sclerotherapy with estimated ethanol concentration was helpful in improving the success rate for treatment of symptomatic simple hepatic cysts. METHODS: Forty-five patients with 52 symptomatic simple hepatic cysts were enrolled in this study. Twenty-one patients (24 cysts, group A) were treated by sclerotherapy without estimated ethanol concentration and 24 patients (28 cysts, group B) with estimated ethanol concentration. The Chi-square test and Mann-Whitney U test were used to compare the difference in characteristics and treatment outcomes of the subjects between these two groups. RESULTS: The mean cyst size before and after treatment were 8.4cm and 2.3cm, respectively, in group A, and 8.2cm and 0.8cm, respectively, in group B. There was no significant difference in the initial size of hepatic cysts between the groups. However, the final size was significantly smaller in group B (P=0.022). The mean ethanol exposure time was 18.3minutes in group B, which was less than that in group A (P<0.001). The success rate was significantly higher in group B (96.4%) than in group A (70.8%) (P=0.03). There were no major complications in either group. CONCLUSION: CT-guided sclerotherapy with estimated ethanol concentration yields better results than those without estimated ethanol concentration in the treatment of symptomatic simple hepatic cysts. PMID- 24210774 TI - Daytime leg pain after overnight continuous positive airway pressure titration. AB - We report a case that showed transitional, severe emergent periodic limb movements during sleep (PLMS) in the first continuous positive airway pressure (CPAP) titration night and mild PLMS in the 3rd and 20th nights of CPAP titration in a 56-year-old woman after she was found to have severe obstructive sleep apnea (OSA). Severe PLMS in the initial CPAP night unexpectedly resulted in acute leg muscle soreness in the second morning. The case suggests that CPAP therapy in patients who suffer from severe OSA may provide a unique opportunity to look into the pathological mechanism of PLMS. PMID- 24210772 TI - Latent class analysis of non-opioid dependent illegal pharmaceutical opioid users in Ohio. AB - BACKGROUND: Increases in non-medical use of pharmaceutical opioids in the U.S. have resulted in increases in opioid dependence and unintentional overdose deaths. We characterize heterogeneity in opioid use patterns among a community based sample of 18-23 year-olds who use non-medical pharmaceutical opioids, yet are not opioid dependent. METHODS: Respondent-driven sampling recruited 390 participants. Latent class analysis stratified by racial/ethnic group identified subgroups of non-medical opioid users based on: six-month frequency of use; number of opioid disorder criteria; oral vs. non-oral administration; number of types of opioids used; use of CNS depressants while under using opioids; and reason for opioid use. Multinomial logistic regression estimated the significance of covariates in predicting class membership. RESULTS: Within whites and non white groups, three classes emerged that were, generally, hierarchically ordered with respect to negative characteristics associated with non-medical opioid use. Within each group, the class with the least negative characteristics also had the highest proportion of individuals who use opioids only to self-medicate a health problem. Within each group's three classes, a larger proportion who had >= 2 opioid abuse and dependence disorder criteria always coincided with a larger proportion who use opioids >= 3 days per week, a larger proportion who used CNS depressants while under the influence of opioids, and a smaller proportion who used opioids only to self-medicate. CONCLUSION: Differences in patterns of opioid use within each racial/ethnic group of young people who are not opioid dependent suggest the need for tailored interventions designed to reduce the risk of transition to opioid dependence. PMID- 24210775 TI - [Should we remove the tubes during surgery for benign diseases?]. PMID- 24210776 TI - [Factors linked to late diagnosis in breast cancer in Sub-Saharan Africa: case of Cote d'Ivoire]. AB - OBJECTIVE: To identify in Ivorian environment, reasons involved in late diagnosis of breast cancer. PATIENTS AND METHODS: Retrospective study over 4 years (January 2008 to December 2011) including 350 patients with breast adenocarcinoma. A questionnaire was created and filled according to the medical files of the patients. Linear regression analysis applied to the data showed concordance between the factors and the delay before diagnosis. RESULTS: Thus 78.9% of the patients sought for care above 10 months with inflammatory cancers (54%) and necrotic ulcerations (18%). Factors found during interview were the lack of financial means (36%), cultural habits with first intent traditional treatment (41.1%), misdiagnosis (7.1%) and lack of therapeutic care. Yet, when comparing each of these factors to the delay, no significant link was found. Chemotherapy was the first therapeutic method. CONCLUSION: In our context, the conjunction of ignorance, poverty and socio-cultural habits were the key factors in late diagnosis of breast cancers in Cote d'Ivoire. PMID- 24210777 TI - Comparisons of colorectal cancer mortality between screening participants and the general population are strongly biased unless an incidence-based mortality approach is used. AB - OBJECTIVES: A common approach in the evaluation of screening for colorectal cancer (CRC) is comparing observed numbers of CRC deaths in screening participants with expected numbers derived from CRC mortality in the general population. We aimed to illustrate and quantify an often-overlooked bias that may occur in such studies if CRC mortality in the general population is not restricted by the date of diagnosis (whereas screening participants by definition do not have a prior CRC diagnosis). STUDY DESIGN AND SETTING: We illustrate and quantify the expected bias using cancer registry data from the United States. RESULTS: Unless an incidence-based mortality approach is used, expected numbers of CRC deaths in screening cohorts (and hence estimated screening effects) are substantially overestimated. Overestimation of expected CRC deaths is most severe (more than fivefold) during the first year of follow-up and rapidly decreases in the subsequent years. Nevertheless, overestimation of 5- and 10-year cumulative numbers of expected CRC deaths is still as high as 60-70% and 20-30%, respectively. Substantial bias even persists if the initial years of follow-up are excluded from the analyses. CONCLUSION: Careful restriction of expected CRC deaths by an incidence-based mortality approach is indispensable for deriving valid screening effect estimates. PMID- 24210778 TI - Resistant hypertension and renal denervation: 3 years on. PMID- 24210779 TI - Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. AB - BACKGROUND: Renal denervation (RDN) with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension. We assessed the long-term antihypertensive effects and safety. METHODS: Symplicity HTN-1 is an open-label study that enrolled 153 patients, of whom 111 consented to follow-up for 36 months. Eligible patients had a systolic blood pressure of at least 160 mm Hg and were taking at least three antihypertensive drugs, including a diuretic, at the optimum doses. Changes in office systolic blood pressure and safety were assessed every 6 months and reported every 12 months. This study is registered with ClinicalTrials.gov, numbers NCT00483808, NCT00664638, and NCT00753285. FINDINGS: 88 patients had complete data at 36 months. At baseline the mean age was 57 (SD 11) years, 37 (42%) patients were women, 25 (28%) had type 2 diabetes mellitus, the mean estimated glomerular filtration rate was 85 (SD 19) mL/min per 1.73 m(2), and mean blood pressure was 175/98 (SD 16/14) mm Hg. At 36 months significant changes were seen in systolic (-32.0 mm Hg, 95% CI 35.7 to -28.2) and diastolic blood pressure (-14.4 mm Hg, -16.9 to -11.9). Drops of 10 mm Hg or more in systolic blood pressure were seen in 69% of patients at 1 month, 81% at 6 months, 85% at 12 months, 83% at 24 months, and 93% at 36 months. One new renal artery stenosis requiring stenting and three deaths unrelated to RDN occurred during follow-up. INTERPRETATION: Changes in blood pressure after RDN persist long term in patients with treatment-resistant hypertension, with good safety. FUNDING: Ardian LLC/Medtronic Inc. PMID- 24210780 TI - Papillary carcinoma within a thyroglossal duct cyst: significance of a central solid component on ultrasound imaging. AB - Malignancy within a thyroglossal duct cyst is rare (1.5% of cases), and most diagnoses are made postoperatively as clinically they are difficult to distinguish from benign neoplasms. We present a case in which a preoperative ultrasound scan showed the presence of a central solid component in a thyroglossal duct cyst, which contained papillary thyroid carcinoma. PMID- 24210781 TI - Coculture of peripheral blood CD34+ cell and mesenchymal stem cell sheets increase the formation of bone in calvarial critical-size defects in rabbits. AB - The reconstruction of large bony defects remains a clinical challenge, and angiogenesis and neovascularisation are being given more attention in bone tissue engineering. In this study we cocultured peripheral blood CD34+ cells (PB-CD34+ cells), an endothelial progenitor cell/haematopoietic stem cell-enriched population, with bone marrow-derived mesenchymal stem cells (MSC) to investigate their potential for bony regeneration. Cocultured cells showed better osteogenic differentiation than MSC alone in vitro. The cocultured cells and MSC sheets were also composited with hydroxyapatite and implanted in calvarial critical-size defects in rabbits. The rabbits were killed before microcomputed tomographic (MicroCT) and histological analysis. The results showed that cocultured cell composites had promoted bony regeneration more efficiently by 8 weeks after implantation. Our results indicate that the coculture of PB-CD34+ cells and MSC increases bony regeneration in calvarial critical-size defects in rabbits, and provide a new promising therapeutic strategy to aid skeletal healing. PMID- 24210782 TI - Inhibitory and bactericidal action of the biocorrosion agents "INCORGAS" and "AMDOR". AB - Inhibiting action of A, B and M-X compositions against hydrosulfide corrosion of carbon steel, hydrogen diffusion through the steel membrane has been studied along with their bactericidal effect with respect to sulfate-reducing bacteria of Desulfomicrobium type. Bactericidal properties of the compositions have been studied in the Postgate medium. Corrosion tests have been made in the NACE medium saturated by hydrogen sulfide and carbon dioxide separately and together by methods of gravimetrical measurements and linear polarization resistance (LRP). Potentiodynamic polarization and electrochemical diffusion method have been used. Steel protection is determined in the inhibited solutions by combined action of corrosion products film and inhibitor. Presence of sulfate-reducing bacteria in medium increases hydrogen diffusion flux through the steel membrane by 2-3 times and essentially stimulates effect of the inhibitors. The inhibiting compositions decrease quantity of sulfate-reducing bacteria (SRB) by 95-98%. The obtained results testify about predominately bacteriostatic action of the inhibiting compositions, which has influence on the enzymatic systems of SRB cells responsible directly for the sulfate reduction because of substantially decreasing the biogenic hydrogen sulfide concentration in the system. PMID- 24210783 TI - A novel three-dimensional adipose-derived stem cell cluster for vascular regeneration in ischemic tissue. AB - BACKGROUND AIMS: Stem cells are one of the most powerful tools in regeneration medicine. However, many limitations remain regarding the use of adult stem cells in clinical applications, including poor cell survival and low treatment efficiency. We describe an innovative three-dimensional cell mass (3DCM) culture that is based on cell adhesion (basic fibroblast growth factor-immobilized substrate) and assess the therapeutic potential of 3DCMs composed of human adipose tissue-derived stromal cells (hASCs). METHODS: For formation of a 3DCM, hASCs were cultured on a substrate with immobilized fibroblast growth factor-2. The angiogenic potential of 3DCMs was determined by immunostaining, fluorescence activated cell sorting and protein analysis. To evaluate the vasculature ability and improved treatment efficacy of 3DCMs, the 3DCMs were intramuscularly injected into the ischemic limbs of mice. RESULTS: The 3DCMs released various angiogenic factors (eg, vascular endothelial growth factor and interleukin-8) and differentiated into vascular cells within 3 days in normal medium. Blood vessel and tissue regeneration was clearly observed through visual inspection in the 3DCM-injected group. hASC injection slowed limb necrosis after treatment, but 50% of the mice ultimately had limb loss within 28 days. Most mice receiving 3DCMs had limb salvage (89%) or mild limb necrosis (11%). CONCLUSIONS: 3DCM culture promotes the efficient vascular differentiation of stem cells, and 3DCM transplantation results in the direct vascular regeneration of the injected cells and an improved therapeutic efficacy. PMID- 24210785 TI - Validation of an automated blood culture system for sterility testing of cell therapy products. AB - BACKGROUND AIMS: Automated blood culture systems are widely used for the detection of microorganisms in cell therapy products. However, they are not validated by the manufacturers for this purpose. The aim of this study was to assess the ability of the Bactec system (Becton-Dickinson, Le Pont-De-Claix, France) to detect the microorganisms that could contaminate cell therapy products. METHODS: Three types of vials and conditions were tested: Plus Aerobic/F and Anaerobic/F media incubated at 35 degrees C and Mycosis IC/F medium incubated at 30 degrees C. All vials were incubated 10 days. We tested 18 microorganisms, including slow growers and some with fastidious nutritional requirements (10 bacteria, four yeasts, four filamentous fungi), each with four inocula (10-10(4) colony-forming units) performed in quintuplicate. RESULTS: The combination of Plus Aerobic/F and Plus Anaerobic/F vials detected all the tested pathogenic bacteria, all the tested Gram-positive skin commensal or environmental bacteria, all the tested yeasts, and three of four tested filamentous fungi. The addition of the Mycosis IC/F vial extended the range of detected microorganisms to one fungal environmental contaminant. Two bacterial environmental contaminants were not detected by our method. Low inocula of the skin contaminant Propionibacterium acnes were detected only after 7 days of incubation. CONCLUSIONS: These data suggest that (i) the prolongation of the incubation time of Plus Aerobic/F and Plus Anaerobic/F vials from 7 to 10 days and (ii) the use of Mycosis IC/F medium make minor contributions in the sterility testing of cell therapy products. We have validated the Bactec method using aerobic and anaerobic vials incubated 7 days at 35 degrees C. PMID- 24210784 TI - Amniotic fluid stem cells prevent beta-cell injury. AB - BACKGROUND AIMS: The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating beta-cell injury and restoring beta-cell function. METHODS: Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. RESULTS: AFSC injection resulted in protection from beta-cell damage and increased beta-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, beta-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining beta-cell mass and function. CONCLUSIONS: Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous beta-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved. PMID- 24210786 TI - Inhibition of non-muscle myosin II leads to G0/G1 arrest of Wharton's jelly derived mesenchymal stromal cells. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have remarkable clinical potential for cell-based therapy. Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) from umbilical cord share unique properties with both embryonic and adult stem cells. MSCs are found at low frequency in vivo, and their successful therapeutic application depends on rapid and efficient large-scale expansion in vitro. Non-muscle myosin II (NMII) has pivotal roles in different cellular activities, such as cell division, migration and differentiation. We performed this study to understand the role of NMII in proliferation and cell cycle progression in WJ-MSCs. METHODS: WJ-MSCs were cultured in the presence of blebbistatin, and cell cycle analysis was performed using flow cytometry, proliferation kinetics, senescence assay and gene expression profile using polymerase chain reaction array. RESULTS: When cultured in the presence of blebbistatin, an inhibitor of NMII adenosine triphosphatase activity, WJ-MSCs exhibited dose-dependent reduction in proliferative potential along with increase in cell size and induction of early senescence. Inhibition of NMII activity also affected cell cycle progression in WJ-MSCs and led to an increase in the percentage of cells in G0/G1 phase with a corresponding reduction in the percentage of cells in G2/M phase. Blebbistatin-induced G0/G1 arrest of WJ-MSCs was further associated with up-regulation of cell cycle inhibitory genes CDKN1A, CDKN2A and CDKN2B and down-regulation of numerous genes related to progression through S and M phases of the cell cycle. CONCLUSIONS: Our study demonstrates that inhibition of NMII activity in WJ-MSCs leads to G0/G1 arrest and alteration in the expression levels of certain key cell cycle-related genes. PMID- 24210787 TI - [Internet and video games among students of Reunion Island in 2010: uses, misuses, perceptions and associated factors]. AB - BACKGROUND: Describe the uses of Internet and video games and quantify associated problematic uses. METHODS: Information on student practices concerning the use of the Internet and video games was collected with a self-administered questionnaire. Problematic uses were identified with specific tools (Young criteria and Tejeiro criteria) and with self-evaluative questions. Information on life events with traumatic potential and use of psychoactive substances was also collected. Logistic regression models were applied to identify possible associated factors. RESULTS: Based on a sample of 1119 subjects, this study showed that students in Reunion Island are very concerned by the uses of the Internet and video games (98% and 46% of respondents). The prevalence of problematic use of the Internet accounted for 6% of respondents. Problematic uses of video games involved 8% of students (18% of gamers). Young people seemed unaware of their problematic practices and were seeking informations. The public respondent was also characterized by vulnerable situations (traumatic events induring their lives, consumption of psychoactive substances). Significant associations (with no identified causality) were examined, in particular between problematic uses of Internet and video games, and life events with traumatic potential. CONCLUSION: These first estimates of the prevalence of problematic use of Internet and video games on Reunion Island are important to promote locally collective awareness about these modern addictions. These results will be used to guide local actions of prevention and care, especially among younger generations. But it is necessary to conduct further work to better identify the factors associated with these problematic uses (determinants, comorbidities addictive...). PMID- 24210788 TI - How to interpret and choose a Bayesian spatial model and a Poisson regression model in the context of describing small area cancer risks variations. AB - BACKGROUND: The statistical Bayesian approach is widely used in disease mapping and Poisson regression. Results differ depending on the underlying hypothesis. Our objective is to give a comprehensive presentation of the tools that can be used to interpret results and choose between the different hypotheses. Data from the Isere cancer registry (France) illustrate this presentation. METHOD: We consider, first, Bayesian models for disease mapping. Classic heterogeneity (Potthoff-Whithinghill statistic) and spatial autocorrelation tests (Moran statistic) of the SIRs, the DIC criteria of the different Bayesian models and finally the comparison of the empirical variance of the unstructured and structured heterogeneity components of the BYM model are considered. The last two criteria are considered for Bayesian Poisson regression including a covariate. Mapping the components of the BYM model with a covariate is also considered. RESULTS: Four cancer sites (prostate, lung, colon-rectum and bladder) in men diagnosed during the 1998-2007 period are used to illustrate our presentation. We show that the different criteria used to interpret and to choose a model give coherent results. CONCLUSION: A relevant interpretation of results is a necessary step in choosing the best-adapted Bayesian model. This choice is easy to make with criteria such as the DIC. The comparison of the empirical variance of the unstructured and structured heterogeneity components of the BYM model is also informative. PMID- 24210789 TI - Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial. AB - OBJECTIVE: To determine whether treatment of low serum vitamin D in pregnant women improves fetal growth indices. STUDY DESIGN: In this open-label randomized clinical trial, 130 Iranian pregnant women (24-26 weeks of gestation) with vitamin D deficiency or insufficiency [25(OH)D <30ng/ml] were divided at random into an intervention group and a control group. The control group received 200mg calcium plus a multivitamin (containing vitamin D3 400U) each day, and the intervention group received 200mg calcium plus a multivitamin (containing vitamin D3 400U) each day, plus vitamin D3 (50,000U) each week for 8 weeks. At delivery, maternal and cord blood 25(OH)D levels, maternal weight gain, neonatal length, neonatal weight and neonatal head circumference were compared between two groups. Serum vitamin D was measured using enzyme-linked immunosorbent assay. A multivariate regression analysis was performed to examine the independent effect of maternal vitamin D level on fetal growth indices. RESULTS: Mean (+/-standard deviation) length (intervention group: 49+/-1.6cm; control group: 48.2+/-1.7cm; p=0.001), head circumference (intervention group: 35.9+/-0.7cm; control group: 35.3+/-1.0cm; p=0.001) and weight (intervention group: 3429+/-351.9g; control group: 3258.8+/-328.2g; p=0.01) were higher in the intervention group compared with the control group. Mean maternal weight gain was higher in the intervention group compared with the control group (13.3+/-2.4kg vs 11.7+/-2.7kg; p=0.006). Multivariate regression analysis for maternal weight gain, neonatal length, neonatal weight and neonatal head circumference showed an independent correlation with maternal vitamin D level. CONCLUSION: Treatment of low serum vitamin D during pregnancy improves fetal growth indices and maternal weight gain. PMID- 24210790 TI - Evaluation of serum anti-Mullerian hormone levels to assess the ovarian reserve in women with severe endometriosis. AB - OBJECTIVE: The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with severe endometriosis, in order to demonstrate the effect of the disease on ovarian reserve. STUDY DESIGN: Prospective case-control study. One hundred and ninety-five patients were enrolled: 130 fertile patients (group A) and 65 patients with stage III and IV endometriosis, diagnosed by laparoscopy and histological examination (group B). AMH serum levels were measured in both groups and were compared using Student's t-test. RESULTS: The two groups were homogenous for main demographic data. Group B had statistically significantly lower mean AMH serum levels (0.97+/-0.59ng/ml) than group A (1.72+/ 0.63ng/ml) (p=0.001). CONCLUSIONS: This study is a demonstration of the damage of endometriosis on ovarian reserve, leading to a form of incipient ovarian failure, which is considered as an early sign of advanced ovarian depletion in young women. These findings suggest that AMH could be used in the follow-up of patients with endometriosis, in order to assess promptly the decrease of ovarian reserve. PMID- 24210791 TI - Anterior needle-guided mesh in advanced pelvic organ prolapse: apical fixation on sacrospinous ligaments. AB - OBJECTIVE: To evaluate whether anterior-apical compartment mesh implants for pelvic floor reconstruction might be safely and effectively anchored to the sacro spinous (SS) ligaments instead of the arcus tendineus fascia pelvis (ATFP). The SS ligaments as anchoring structures for centro-apical support mesh fixation are thought to be stronger than the ATFP and we presumed that anterior mesh fixation to the SS ligament might be feasible, safe and effective. STUDY DESIGN: Patients with advanced anterior-apical pelvic floor prolapse, referred for mesh reconstruction and having poor ATFP were enrolled to this study. For these patients the posterior arms of the anterior mesh were fixed to the SS ligaments. Data regarding cure, complications and patient's satisfaction were collected prospectively: patients were interviewed and examined at the end of the first and third post-operative months, and interviewed again at the study conclusion. RESULTS: Of 72 patients who were asked to participate in this study, 44 had rather un-palpable ATFP, and SS ligament fixation was performed. The mean follow up duration was 12 months (range: 10-43). No significant intra- or post-operative complications were recorded. The POP-Q points measurements showed marked improvements: the average delta for the Ba point was 7.4cm, for the Bp point 4.7cm, and for the C point 7.9cm. These differences were all statistically significant. Bladder overactivity symptoms, namely urgency, frequency and nocturia, were all found to be reduced significantly, and so was the sexual discomfort rate. Fecal incontinence, pelvic pain and constipation rates were reduced as well, but these did not reach statistical significance. CONCLUSIONS: This rather small study suggests that anterior pelvic floor meshes might be anchored safely and successfully to the SS ligament, aiming to achieve improved centro-apical support of the vaginal apex and the anterior wall by an anterior pelvic floor approach. PMID- 24210792 TI - Spatial organization of xylem cell walls by ROP GTPases and microtubule associated proteins. AB - Proper patterning of cellulosic cell walls is critical for cell shaping and differentiation of plant cells. Cortical microtubule arrays regulate the deposition patterns of cellulose microfibrils by controlling the targeting and trajectory of cellulose synthase complexes. Although some microtubule-associated proteins (MAPs) regulate the arrangement of cortical microtubules, knowledge about the overall mechanism governing the spacing of cortical microtubules is still limited. Recent studies reveal that ROP GTPases and MAPs spatially regulate the assembly and disassembly of cortical microtubules in developing xylem cells, in which localized secondary cell walls are deposited. Here, we review recent insights into the regulation of xylem cell wall patterning by cortical microtubules, ROP GTPases, and MAPs. PMID- 24210794 TI - Muscular responses to handle perturbation with different glove condition. AB - Effect of wearing gloves on timely muscle reaction to stabilize handle perturbation was investigated. Thirteen adults gripped a horizontal overhead handle to which an upward force was applied at a random time. Muscle reaction time, integrated EMGs for eight muscles, and handle displacement were compared among three glove conditions affecting the coefficient of friction (COF=0.32, 0.50, and 0.74 for the polyester glove, bare hand, and latex glove, respectively). Lower COF increased the integrated EMGs and handle displacement until stabilization of the perturbed handle. The low-friction glove resulted in 16% (p=.01) greater muscular effort and 20% (p=.002) greater handle displacement, compared to the high-friction glove. Muscle reaction time was not influenced by glove condition. Cutaneous sensation and reflex eliciting forearm muscle activity appear to play an important role in detecting and responding to the perturbation initially, while the forearm and latissimus dorsi muscles primarily contribute to stabilizing the perturbed handle compared to other shoulder and upper arm muscles. Therefore, low-friction gloves, cutaneous sensory dysfunction, and weakened forearm and latissimus dorsi muscles may jeopardize persons' ability to stabilize a grip of a handle after perturbation. PMID- 24210793 TI - GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine intoxicated mice. AB - Innate and adaptive immune responses can speed nigrostriatal neurodegeneration in Parkinson's disease (PD). We posit that GM-CSF can attenuate such responses. In 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral dopaminergic neurons coincident with altered microglial morphologies and regulatory T cell (Treg) induction. Adoptive transfer of GM-CSF-induced Treg to MPTP mice protected nigral neurons. Gene expression analyses revealed novel immune-based neuronal protection pathways linked to the upregulation of IL-27. The results provide evidence that GM-CSF modulation of immunity could be of clinical benefit for PD. PMID- 24210795 TI - Loading and knee flexion after stroke: Less does not equal more. AB - It is believed that force feedback can modulate lower extremity extensor activity during gait. The purpose of this research was to determine the role of limb loading on knee extensor excitability during the late stance/early swing phase of gait in persons post-stroke. Ten subjects with chronic hemiparesis post-stroke participated in (1) seated isolated quadriceps reflex testing with ankle loads of 0-0.4Nm/kg and (2) gait analysis on a treadmill with 0%, 20% or 40% body weight support. Muscle reflex responses were recorded from vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) during seated testing. Knee kinematics and quadriceps activity during late stance/early swing phase of gait were compared across loading conditions. Although isolated loading of the ankle plantarflexors at 0.2Nm/kg reduced VM prolonged response (p=0.04), loading did not alter any other measure of quadriceps excitability (all p>0.08). During gait, the use of BWS did not influence knee kinematics (p=0.18) or muscle activity (all p>0.17) during late stance/early swing phase. This information suggests that load sensed at the ankle has minimal effect on the ipsilateral quadriceps of individuals post stroke during late stance. It appears that adjusting limb loading during rehabilitation may not be an effective tool to address stiff-knee gait following stroke. PMID- 24210796 TI - Slow expiration reduces sternocleidomastoid activity and increases transversus abdominis and internal oblique muscle activity during abdominal curl-up. AB - The aim of this study was to investigate the effects of quiet inspiration versus slow expiration on sternocleidomastoid (SCM) and abdominal muscle activity during abdominal curl-up in healthy subjects. Twelve healthy subjects participated in this study. Surface electromyography (EMG) was used to collect activity of bilateral SCM, rectus abdominis (RA), external oblique (EO), and transversus abdominis/internal oblique (TrA/IO) muscles. A paired t-test was used to determine significant differences in the bilateral SCM, RF, EO, and TrA/IO muscles between abdominal curl-up with quiet inspiration and slow expiration. There were significantly lower EMG activity of both SCMs and greater EMG activity of both IOs during abdominal curl-up with slow expiration, compared with the EMG activity of both SCMs and IOs during abdominal curl-up with quiet inspiration (p<.05). The results of this study suggest that slow expiration would be recommended during abdominal curl-up for reduced SCM activation and selective activation of TrA/IO in healthy subjects compared with those in abdominal curl up with quiet inspiration. PMID- 24210797 TI - The latest evidence on target selection in deep brain stimulation for Parkinson's disease. AB - Deep brain stimulation (DBS) is one of the most promising neuromodulatory techniques to gain momentum over the last 20years, with significant evidence showing the benefit of DBS for Parkinson's disease (PD). However, many questions still exist pertaining to the optimal placement of stimulation contacts. This paper aims to review the latest and most relevant studies evaluating subthalamic nucleus (STN) and globus pallidus interna (GPi) stimulation. Additionally, it aims to shine a light on several of the lesser-known targets with mounting evidence of efficacy. Referenced literature for the main body of the article was gathered from Medline and PubMed databases. Results were limited to "full text", "English language" and publications from 1999 onwards. Case reports were excluded. The current evidence irrefutably demonstrates the benefits of both STN and GPi DBS on Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores, with very similar outcomes seen after 1-2years. Currently, it appears the greatest differences lie in the associated adverse effects. STN DBS was associated with a greater reduction in dopamine replacement therapy, but also appeared to have more negative effects on speech and mood. Meanwhile, in regards to alternative targets, the pedunculopontine nucleus has shown promising improvement in axial symptoms, while the ventral intermediate nucleus has demonstrated significant efficacy at suppressing tremor, and the caudal zona incerta may be superior to the STN and GPi in improving UPDRS-III scores. Due to the complexity of Parkinson's disease, an individual disease profile must be determined in a patient-by-patient fashion such that appropriate targets can be selected accordingly. PMID- 24210798 TI - Changes in serum interleukin-33 levels in patients with acute cerebral infarction. AB - Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. PMID- 24210799 TI - Spontaneous cervical intradural disc herniation. AB - Cervical intradural disc herniation (IDH) is a rare condition with very few case reports in the literature. We report a 64-year-old man who presented with sudden onset neck pain and rapidly progressing weakness in the left upper and lower limb. There was no history of trauma. MRI of the cervical spine showed a C6-C7 disc prolapse, for which he underwent a C6-C7 discectomy and fusion with bone graft through an anterior cervical approach. To our knowledge, all patients with a cervical IDH reported in the literature have a traumatic etiology. To the best of our knowledge, we report the first patient with a spontaneous cervical IDH. PMID- 24210800 TI - Brainstem encephalitis caused by Coxiella burnetii. AB - Coxiella burnetii is the causative agent of Q fever, which rarely causes neurologic symptoms. We describe a patient who presented with progressive sensory changes, dizziness, and motor weakness. The cerebrospinal fluid revealed pleocytosis, and MRI indicated the presence of a diffuse brain stem lesion. An indirect immunofluorescence test revealed antibodies against C. burnetii. The symptoms improved with antibiotics against C. burnetii. Q fever should be considered as a possible etiology of brainstem encephalitis. PMID- 24210801 TI - Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection. AB - We report a case of unilateral blindness and panophthalmoplegia after hyaluronic acid injection into the dorsum of the nose in a healthy young woman. Microspheres of hyaluronic acid are popular fillers for facial rejuvenation. While ocular side effects from injections in the nose and face have been reported following turbinate injection, rhinoplasty and infraorbital nerve block, ocular side effects from injection into the dorsum of the nose are extremely rare. We presume that the symptoms were due to obstruction of the branches of the ophthalmic artery. Under high injection pressure, the microspheres travelled to the ophthalmic artery and were propelled by the blood flow to the central retinal artery and the anterior and posterior long ciliary arteries, leading to her symptoms. Alternatively, there are several arterio-venous anastomotic channels in the nasal mucosa that aid heat exchange. These may have been the conduit for reflux of the filler into the arterial side of the regional circulation. Physicians must remain aware of serious complications during cosmetic injections to this region. PMID- 24210802 TI - Deep brain stimulator-induced diaphoresis in Parkinson's disease patients. AB - We report an unusual finding of bilateral facial and corporeal diaphoresis and sensation of heat during deep brain stimulation in two patients. Stimulation of the hypothalamospinal tract located medial to the subthalamic nucleus is likely to be responsible for this side effect. PMID- 24210803 TI - Acute inferior homonymous quandrantanopia in a 71-year-old woman. AB - A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex. PMID- 24210804 TI - Successful resection of anterior and anterolateral lesions at the craniovertebral junction using a simple posterolateral approach. AB - Tumors at the craniovertebral junction (CVJ) often present a challenge due to proximity to vital neurovascular structures. In the last few decades, many authors have proposed complex surgical approaches to access pathologies located anterior or anterolateral to the CVJ with the hopes of reducing morbidity. We propose that the simple posterolateral approach in a semi-sitting position can be used to resect most anterior and anterolateral CVJ tumors safely and effectively. We retrospectively reviewed the clinical series of 10 patients treated by the senior author using the posterolateral suboccipital approach to treat anterior or anterolateral CVJ pathologies. We describe our surgical techniques, outcomes, and present illustrative patients. Gross total resection was achieved in eight patients (80%). Good functional outcome (Glasgow Outcome Scale 4-5) was obtained in all patients. Preoperative symptoms and deficits were improved (78%) or stable (22%) in all patients. There was one (10%) surgical complication that was cerebrospinal fluid leak requiring reoperation. There was no permanent morbidity or mortality in this series. There were two (20%) medical complications including deep vein thrombosis and pulmonary embolus. There were three (30%) transient neurologic complications, dysphagia in two and dysarthria in one, all of which resolved completely in early follow-up. The majority of anterior or anterolateral CVJ lesions can be successfully removed using the simple posterolateral approach. PMID- 24210805 TI - Post-surgical thoracic pseudomeningocele causing spinal cord compression. AB - Pseudomeningoceles are extradural cerebrospinal fluid collections categorized into three groups: traumatic, congenital, and iatrogenic. Iatrogenic pseudomeningoceles occur after durotomy, usually after cervical or lumbar spine surgery. Although many remain asymptomatic, pseudomeningoceles can compress or herniate the spinal cord and nerve roots. We present a 57-year-old woman who had a thoracic laminectomy and discectomy. Two weeks after surgery, she presented with lower extremity weakness and gait difficulty. Physical examination revealed hyperreflexia and a T11 sensory level. MRI revealed a pseudomeningocele compressing the thoracic spinal cord. The patient underwent surgical drainage of the cyst. On follow-up, she had complete resolution of her symptoms, and MRI did not show a residual lesion. To our knowledge, this is the second documented post operative pseudomeningocele causing symptomatic spinal cord compression of the thoracic spine. In this article, a review of the literature is presented, including four reported patients with post-traumatic pseudomeningocele causing myelopathic symptoms and 20 patients with iatrogenic pseudomeningocele that resulted in neurological decline due to herniation or compression of neural tissue. Treatment options for these lesions include conservative management, epidural blood patch, lumbar subarachnoid drainage, and lumbo-peritoneal shunt placement. Surgical repair, usually by primary dural closure, remains the definitive treatment modality for iatrogenic symptomatic pseudomeningoceles. PMID- 24210806 TI - Brain metastasis from extramammary Paget's disease of the scrotum. AB - We present to our knowledge the first patient with histopathologically proven brain metastasis from extramammary Paget's disease (EMPD) and discuss the effect of brain radiation therapy for this condition. A 68-year-old man presented to our hospital with headache and gait disturbance. Brain MRI showed multiple enhancing mass lesions, and two large cystic lesions in the left cerebellum. The patient had been diagnosed with scrotal Paget's disease 3 months previously but no further management had been performed due to his refusal. The patient underwent stereotactic aspiration and biopsy of the two large cystic lesions. A histopathological examination revealed that the tumor was a metastatic adenocarcinoma. Immunohistochemical staining revealed that the tumor cells were strongly positive for cytokeratin 7 and moderately positive for carcinoembryonic antigen and gross cystic disease fluid protein 15. These findings were similar to those of his scrotal skin lesions and were consistent with metastatic EMPD. The patient underwent brain radiation therapy with a total radiation dose of 30 Gy in 10 fractions. The patient improved neurologically so as to be self-ambulatory, and a mild improvement in the metastatic tumors was found on follow-up MRI. We had planned systemic chemotherapy, but the patient died of acute respiratory failure 2 months after radiation therapy. PMID- 24210807 TI - Endoscopic transnasal resection of ameloblastoma with intracranial extension. AB - Ameloblastoma is a rare odontogenic tumor with characteristics of epithelial tissue that produces enamel for the developing tooth. This lesion is generally considered benign, but has malignant forms that invade locally and metastasize. We present a 60-year-old man with maxillary ameloblastoma that after multiple recurrences developed intracranial extension with dural involvement of the middle cranial fossa and was treated by endoscopic transnasal resection followed by radiation therapy. Our technique and intraoperative findings are described with a review of the literature on intracranial ameloblastoma. This patient represents a unique account of endoscopic transnasal resection being utilized in the treatment of intracranial extension of ameloblastoma and demonstrates potential for application in similar cases. PMID- 24210808 TI - 213Bi-anti-EGFR radioimmunoconjugates and X-ray irradiation trigger different cell death pathways in squamous cell carcinoma cells. AB - INTRODUCTION: Treatment of patients with squamous cell carcinoma of head and neck is hampered by resistance of tumor cells to irradiation. Additional therapies enhancing the effect of X-ray irradiation may be beneficial. Antibodies targeting EGFR have been shown to improve the efficacy of radiation therapy. Therefore, we analyzed cytotoxicity of (213)Bi-anti-EGFR immunoconjugates in combination with X ray irradiation. METHODS: The monoclonal anti-EGFR antibody matuzumab was coupled to CHX-A"-DTPA forming stable complexes with (213)Bi. Cytotoxicity of X-ray radiation, of treatment with (213)Bi-anti-EGFR monoclonal antibodies (MAb) or of a combined treatment regimen was assayed using cell proliferation and colony formation assays in UD-SCC5 cells. Key proteins of cell-cycle arrest and cell death were examined by Western blot analysis. Cell cycle analysis was performed by flow cytometry. DNA double-strand breaks were detected via gammaH2AX and quantified using DefiniensTM software. RESULTS: Irradiation with X-rays or treatment with (213)Bi-anti-EGFR-MAb resulted in median lethal dose (LD50) values of 12 Gy or 130 kBq/mL, respectively. Treatment with 37 kBq/mL of (213)Bi-anti EGFR-MAb or 2 Gy of X-rays had only little effect on colony formation of UD-SCC5 cells. In contrast, a combined treatment regimen (37 kBq/mL plus 2 Gy) significantly decreased colony formation and enhanced the formation of DNA double strand breaks. As revealed by flow cytometry, radiation treatments caused accumulation of cells in the G0/G1 phase. Both treatment with (213)Bi-anti-EGFR immunoconjugates and application of the combined treatment regimen triggered activation of genes of signaling pathways involved in cell-cycle arrest and induction of apoptosis like p21/Waf, GADD45, Puma and Bax, which were only marginally modulated by X-ray irradiation of cells. CONCLUSIONS: (213)Bi-anti EGFR-MAb enhances cytotoxicity of X-ray irradiation in UD-SCC5 cells most probably due to effective induction of DNA double-strand breaks. Induction of genes involved in cell-cycle arrest and cell death is almost exclusively due to (213)Bi-anti-EGFR-MAb and seems to be independent of p53 function. PMID- 24210809 TI - [The role of multimodality imaging in the diagnosis of constrictive pericarditis]. AB - Constrictive pericarditis is a rare heart disease. The diagnosis remains a challenge. In fact, this illness can mimic restrictive cardiomyopathy. Echo Doppler evaluation helps to establish the diagnosis of constriction; however, this technique is limited in its ability to image the entire pericardium because of its limited acoustic windows by air or bone of thorax. In addition, it is an operator-dependent exploration. Scanner and magnetic resonance imaging provide a large field of view and excellent images, showing the increased pericardial thickness and septal motion abnormalities. This review will consider the emerging role of these imaging modalities in the constrictive pericarditis diagnosis. PMID- 24210810 TI - Reversible overexpression of bace1-cleaved neuregulin-1 N-terminal fragment induces schizophrenia-like phenotypes in mice. AB - BACKGROUND: Neuregulin-1 (Nrg1) is a pleiotropic signaling molecule that regulates neural development, and mutation of Nrg1 is a risk factor for schizophrenia. Cleavage of type I beta1 Nrg1 isoform by Bace1 releases a secreted N-terminal fragment (Nrg1-ntfbeta), which can bind to a cognate ErbB receptor to activate the specific signaling cascade. This study aimed to determine whether increased expression of Nrg1 is beneficial for brain development and functions. METHODS: We generated transgenic mice overexpressing this fragment under the control of a tetracycline-inducible promoter and examined functional and behavioral changes in mice upon reversible expression of the transgene. RESULTS: Increased expression of full-length Nrg1 in mouse neurons has been previously shown to enhance myelination in the central nervous system. Overexpressing Nrg1 ntfbeta enhanced the expression of myelin proteins, consistent with the expected activation of the Nrg1 signaling pathway by Nrg1-ntfbeta. Contrary to expectations, overexpressing Nrg1-ntfbeta transgene caused schizophrenia-like behaviors in transgenic mice, and these abnormal behaviors were reversible if the expression of the Nrg1-ntfbeta transgene was turned off. Our molecular assay suggests that protein levels of N-methyl-D-aspartate receptors are reduced in this transgenic mouse model, which might underlie the observed social and cognitive behavioral impairments. CONCLUSIONS: Our results indicate that overexpressing the secreted form of Nrg1 is sufficient to cause schizophrenia like behaviors in a mouse model, meaning the effect is independent of the transmembrane and C-terminal domains of Nrg1. Hence, genetic gain-of-function mutations of Nrg1 are also risk factors for schizophrenia. PMID- 24210811 TI - Characterization of betaine aldehyde dehydrogenase (BetB) as an essential virulence factor of Brucella abortus. AB - The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization rates compared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During internalization, compared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected cells compared to the wild-type cells. In mice, the betB mutant was predominantly cleared from spleens compared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis. PMID- 24210812 TI - Genotypes and antibiotic resistance of canine Campylobacter jejuni isolates. AB - Campylobacter jejuni is the most important cause of bacterial gastroenteritis in humans. It is a commensal in many wild and domestic animals, including dogs. Whereas genotypes of human and chicken C. jejuni isolates have been described in some detail, only little information on canine C. jejuni genotypes is available. To gain more information on genotypes of canine C. jejuni and their zoonotic potential, isolates from routine diagnostics of diarrheic dogs as well as isolates of a prevalence study in non-diarrheic dogs were analyzed. Prevalence of thermophilic Campylobacter among non-diarrheic dogs was 6.3% for C. jejuni, 5.9% for Campylobacter upsaliensis and 0.7% for Campylobacter coli. The C. jejuni isolates were genotyped by multi locus sequence typing (MLST) and flaB typing. Resistance to macrolides and quinolones was genetically determined in parallel. Within the 134 genotyped C. jejuni isolates 57 different sequence types (ST) were found. Five STs were previously unrecognized. The most common STs were ST-48 (11.2%), ST-45 (10.5%) and ST-21 (6.0%). Whereas no macrolide resistance was found, 28 isolates (20.9%) were resistant to quinolones. ST-45 was significantly more prevalent in diarrheic than in non-diarrheic dogs. Within the common time frame of isolation 94% of the canine isolates had a ST that was also found in human clinical isolates. In conclusion, prevalence of C. jejuni in Swiss dogs is low but there is a large genetic overlap between dog and human isolates. Given the close contact between human and dogs, the latter should not be ignored as a potential source of human campylobacteriosis. PMID- 24210813 TI - Ultrasonic enhancement of battery diffusion. AB - It has been demonstrated that sonic energy can be harnessed to enhance convection in Galvanic cells during cyclic voltammetry; however, the practical value of this approach is limited due to the lack of open volumes for convection patterns to develop in most batteries. This study evaluates the ability of ultrasonic waves to enhance diffusion in membrane separators commonly used in sandwich architecture batteries. Studies include the measuring of open-circuit performance curves to interpret performances in terms of reductions in concentration overpotentials. The use of a 40 kHz sonicator bath can consistently increase the voltage of the battery and reduce overpotential losses up to 30%. This work demonstrates and quantifies battery enhancement due to enhanced diffusion made possible with ultrasonic energy. PMID- 24210814 TI - Sonication assisted assemblage of exotic polymer supported nanostructured bio hybrid system and prospective application. AB - This work was focused on sonication mediated immobilization of porcine pancreatic lipase (PPL) onto poly(ethylene glycol) supported silver-iron oxide hybrid nanoparticles (PEG-Ag/IONPs). Selected process parameters of sonication were optimized using response surface methodology. Sonication assisted assemblage of spherical PEG-Ag/IONPs and consequent evolution of nanorods post PPL immobilization were documented. The efficacy of the reported immobilization strategy was attested by the increased thermostability, storage stability and enhanced activity of the biocatalyst, suggestive of plausible structural modulations post immobilization. The commercial prospect of the antibacterial and magnetically recyclable system was vouched by its excellent compatibility with some commercial detergents for oil de-staining. PMID- 24210815 TI - Local functional overconnectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders. AB - Although growing evidence indicates atypical long-distance connectivity in autism spectrum disorder (ASD), much less is known about local connectivity, despite conjectures that local overconnectivity may be causally involved in the disorder. Using functional connectivity MRI and graph theory, we found that local functional connectivity was atypically increased in adolescents with ASD in temporo-occipital regions bilaterally. Posterior overconnectivity was found to be associated with higher ASD symptom severity, whereas an ASD subsample with low severity showed frontal underconnectivity. The findings suggest links between symptomatology and local connectivity, which vary within the autism spectrum. PMID- 24210816 TI - Autoregulation of connexin43 gap junction formation by internally translated isoforms. AB - During each heartbeat, intercellular electrical coupling via connexin43 (Cx43) gap junctions enables synchronous cardiac contraction. In failing hearts, impaired Cx43 trafficking reduces gap junction coupling, resulting in arrhythmias. Here we report that internal translation within Cx43 (GJA1) mRNA occurs, resulting in truncated isoforms that autoregulate Cx43 trafficking. We find that at least four truncated Cx43 isoforms occur in the human heart, with a 20 kDa isoform predominating. In-frame AUG codons within GJA1 mRNA are the translation initiation sites and their ablation arrests trafficking of full length Cx43. The 20 kDa isoform is sufficient to rescue this trafficking defect in trans, suggesting it as a trafficking chaperone for Cx43. Limiting cap dependent translation through inhibition of mTOR enhances truncated isoform expression, increasing Cx43 gap junction size. The results suggest that internal translation is a mechanism of membrane protein autoregulation and a potent target for therapies aimed at restoring normal electrical coupling in diseased hearts. PMID- 24210817 TI - SHARPIN regulates uropod detachment in migrating lymphocytes. AB - SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1), which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte function-associated antigen-1 (LFA-1), a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells. PMID- 24210818 TI - 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. AB - To date, estrogen is the only known endogenous estrogen receptor (ER) ligand that promotes ER+ breast tumor growth. We report that the cholesterol metabolite 27 hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in ER+ breast cancer patients, 27HC content in normal breast tissue is increased compared to that in cancer-free controls, and tumor 27HC content is further elevated. Increased tumor 27HC is correlated with diminished expression of CYP7B1, the 27HC metabolizing enzyme, and reduced expression of CYP7B1 in tumors is associated with poorer patient survival. Moreover, 27HC is produced by MCF-7 cells, and it stimulates cell-autonomous, ER-dependent, and GDNF-RET dependent cell proliferation. Thus, 27HC is a locally modulated, nonaromatized ER ligand that promotes ER+ breast tumor growth. PMID- 24210819 TI - Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. AB - Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Abeta) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Abeta deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Abeta. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Abeta-positive veins, but not on Abeta-positive arteries or Abeta-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Abeta in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of Abeta load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate Abeta within the lumen of veins and constitute a potential therapeutic target in AD. PMID- 24210820 TI - SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease. AB - Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease. PMID- 24210821 TI - Brain hyperconnectivity in children with autism and its links to social deficits. AB - Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism. PMID- 24210822 TI - Specificity of monosynaptic sensory-motor connections imposed by repellent Sema3E PlexinD1 signaling. AB - In mammalian spinal cord, group Ia proprioceptive afferents form selective monosynaptic connections with a select group of motor pool targets. The extent to which sensory recognition of motor neurons contributes to the selectivity of sensory-motor connections remains unclear. We show here that proprioceptive sensory afferents that express PlexinD1 avoid forming monosynaptic connections with neurons in Sema3E(+) motor pools yet are able to form direct connections with neurons in Sema3E(off) motor pools. Anatomical and electrophysiological analysis of mice in which Sema3E-PlexinD1 signaling has been deregulated or inactivated genetically reveals that repellent signaling underlies aspects of the specificity of monosynaptic sensory-motor connectivity in these reflex arcs. A semaphorin-based system of motor neuron recognition and repulsion therefore contributes to the formation of specific sensory-motor connections in mammalian spinal cord. PMID- 24210823 TI - DUB-resistant ubiquitin to survey ubiquitination switches in mammalian cells. AB - The ubiquitin-modification status of proteins in cells is highly dynamic and maintained by specific ligation machineries (E3 ligases) that tag proteins with ubiquitin or by deubiquitinating enzymes (DUBs) that remove the ubiquitin tag. The development of tools that offset this balance is critical in characterizing signaling pathways that utilize such ubiquitination switches. Herein, we generated a DUB-resistant ubiquitin mutant that is recalcitrant to cleavage by various families of DUBs both in vitro and in mammalian cells. As a proof-of principle experiment, ectopic expression of the uncleavable ubiquitin stabilized monoubiquitinated PCNA in the absence of DNA damage and also revealed a defect in the clearance of the DNA damage response at unprotected telomeres. Importantly, a proteomic survey using the uncleavable ubiquitin identified ubiquitinated substrates, validating the DUB-resistant ubiquitin expression system as a valuable tool for interrogating cell signaling pathways. PMID- 24210824 TI - Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus. AB - The impact of RNA viruses on the posttranscriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is to the result of the expression of large amounts of viral RNAs that contain high affinity HuR binding sites in their 3' UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a molecular mechanism of virus-host interaction that probably has a significant impact on virus replication, cytopathology, and pathogenesis. PMID- 24210825 TI - High-resolution replication profiles define the stochastic nature of genome replication initiation and termination. AB - Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci. PMID- 24210826 TI - High-frequency promoter firing links THO complex function to heavy chromatin formation. AB - The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence in situ hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the THO complex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation. PMID- 24210827 TI - Roles of exonucleases and translesion synthesis DNA polymerases during mitotic gap repair in yeast. AB - Transformation-based gap-repair assays have long been used to model the repair of mitotic double-strand breaks (DSBs) by homologous recombination in yeast. In the current study, we examine genetic requirements of two key processes involved in DSB repair: (1) the processive 5'-end resection that is required to efficiently engage a repair template and (2) the filling of resected ends by DNA polymerases. The specific gap-repair assay used allows repair events resolved as crossover versus noncrossover products to be distinguished, as well as the extent of heteroduplex DNA formed during recombination to be measured. To examine end resection, the efficiency and outcome of gap repair were monitored in the absence of the Exo1 exonuclease and the Sgs1 helicase. We found that either Exo1 or Sgs1 presence is sufficient to inhibit gap-repair efficiency over 10-fold, consistent with resection-mediated destruction of the introduced plasmid. In terms of DNA polymerase requirements for gap repair, we focused specifically on potential roles of the Pol zeta and Pol eta translesion synthesis DNA polymerases. We found that both Pol zeta and Pol eta are necessary for efficient gap repair and that each functions independently of the other. These polymerases may be involved either in the initiation of DNA synthesis from the an invading end, or in a gap filling process that is required to complete recombination. PMID- 24210828 TI - The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin. AB - BACKGROUND: Dyspepsia develops in healthy volunteers after withdrawal of proton pump inhibitors. This phenomenon, attributed to rebound acid hypersecretion, is thought to be mediated by reflex hypergastrinemia. AIMS: To measure fasting and postprandial gastrin in patients on long-term proton-pump inhibitor treatment and correlate gastrin levels with the duration of treatment and other potential predictors. METHODS: In this cross sectional study patients, with erosive esophagitis, on long-term proton-pump inhibitor treatment and healthy controls underwent gastrin measurements at baseline and four times following a meal and Helicobacter pylori status was determined. RESULTS: A total of 100 patients and 50 controls were studied. Pre- and postprandial gastrin levels were higher in patients (p<0.001). No significant correlation was found between the area under the gastrin-curve and the treatment duration. Female patients had significantly higher gastrin levels than males pre- and postprandial, whereas such differences was not found in the control group. Female gender was the only independent predictor of s-gastrin levels (OR 2.50 compared to males, 95% CI: 1.08-5.76, p=0.032) in the patient group. CONCLUSION: Gastrin values were higher in patients compared to controls. There was no correlation between gastrin levels and treatment duration. Female patients had significantly higher gastrin values than males. PMID- 24210829 TI - Clinicopathologic characteristics and outcomes of penile cancer treated at tertiary care centers in the Western United States. AB - BACKGROUND: This article reports on the experience with penile squamous cell carcinoma (PSCC) in a unique multiethnic patient population from Los Angeles, California, with regard to treatments rendered and clinical outcomes. PATIENTS AND METHODS: Available clinical, pathologic, and treatment information for PSCC patients treated at 3 hospitals associated with the University of Southern California from 1991 to 2011 was retrospectively reviewed. Associations of patient variables with prognosis were assessed using univariable and multivariable analyses. RESULTS: Of the 95 PSCC patients identified, clinicopathologic and outcome information was available on 89 men (median age, 53 years; median follow-up, 23 months). National minorities comprised 76.4% of the cohort with 57.3% Hispanics accounting for all patients. Presence of poorly differentiated tumors was associated with higher tumor stage (P = .020), nodal metastasis (P = .016), distant metastasis (P = .004), and advanced AJCC disease stage (P = .001). Univariate analysis showed that tumor (P = .008), nodal (P = .033), and metastasis (P < .001) stage, and tumor differentiation (P = .010) were associated with survival. When categorized according to the AJCC classification, patients with >= stage III disease had worse outcomes (P = .006). Type of primary therapy delivered did not affect outcomes. AJCC disease stage was independently prognostic in multivariable analysis (P = .035). CONCLUSION: These results confirm associations of several clinicopathologic factors with PSCC outcomes, although the presented population differs from others previously described from the United States with a relatively higher proportion of Hispanic men. This highlights the need for studies on the effects of race, cultural, health, and behavioral patterns on PSCC outcomes in multiethnic populations. PMID- 24210830 TI - Repair of posterior mitral valve prolapse with a novel leaflet plication clip in an animal model. AB - OBJECTIVE: Recently, there has been increased interest in minimally invasive mitral valve prolapse repair techniques; however, these techniques have limitations. A new technique was developed for treating mitral valve prolapse that uses a novel leaflet plication clip to selectively plicate the prolapsed leaflet segment. The clip's efficacy was tested in an animal model. METHODS: Yorkshire pigs (n = 7) were placed on cardiopulmonary bypass (CPB), and mitral valve prolapse was created by cutting chordae supporting the P2 segment of the posterior leaflet. Animals were weaned off CPB and mitral regurgitation (MR) was assessed echocardiographically. CPB was reinitiated and the plication clip was applied under direct vision to the P2 segment to eliminate the prolapse. The animals survived for 2 hours. Epicardial echocardiography was obtained before and after prolapse creation and 2 hours after clip placement to quantify MR grade and vena contracta area. Posterior leaflet mobility and coaptation height were analyzed before and after clip placement. RESULTS: There were no cases of clip embolization. Median MR grade increased from trivial (0-1.5) to moderate-severe after MR creation (2.5-4+) (P < .05), and decreased to mild after clip placement (0-3+) (P < .05). Vena contracta area tended to increase after cutting the chordae and decrease after clip placement: 0.08 +/- 0.10 cm(2) versus 0.21 +/- 0.15 cm(2) versus 0.16 +/- 0.16 cm(2) (P = .21). The plication clip did not impair leaflet mobility. Coaptation height was restored to baseline: 0.51 +/- 0.07 cm versus 0.44 +/- 0.18 cm (P = 1.0). CONCLUSIONS: The leaflet plication clip can treat mitral valve prolapse in an animal model, restoring coaptation height without affecting leaflet mobility. This approach is a simple technique that may improve the effectiveness of beating-heart and minimally invasive valve surgery. PMID- 24210831 TI - Dexamethasone levels predict cortisol response after infant cardiopulmonary bypass. AB - OBJECTIVES: We sought to evaluate whether there is variability in blood dexamethasone levels after a standard 1 mg/kg dose of dexamethasone administered before infant cardiopulmonary bypass. We hypothesized that postoperative dexamethasone drug levels are highly variable, and that the infant stress response is related inversely to the amount of dexamethasone measured in the blood. METHODS: Thirty-two infants (age, <=365 days) received 1 mg/kg of dexamethasone before cardiopulmonary bypass (CPB) initiation. Blood was analyzed for cortisol, adrenocorticotropin, and interleukin (IL)-6, IL-8, and IL-10 levels after anesthesia induction, after CPB, after intensive care unit (ICU) arrival, and 4, 8, 12, and 24 hours after surgery. Patients were grouped as high dexamethasone (>=15 MUg/dL) or low dexamethasone (<15 MUg/dL) based on their level at ICU arrival. RESULTS: Dexamethasone levels varied significantly between the high (n = 22) and low (n = 10) dexamethasone groups throughout the entire postoperative course and were correlated highly with cortisol response. Patients with high dexamethasone levels had postoperative cortisol levels that were lower than their pre-CPB baseline cortisol levels. Cortisol levels remained low throughout the first 24 postoperative hours even after dexamethasone levels neared zero. There were no significant differences between groups in the duration of mechanical ventilation or ICU length of stay. CONCLUSIONS: Dexamethasone levels are highly variable at ICU arrival, despite standardized 1 mg/kg dosing before CPB initiation. PMID- 24210832 TI - Discussion. PMID- 24210834 TI - Comparing robot-assisted thoracic surgical lobectomy with conventional video assisted thoracic surgical lobectomy and wedge resection: results from a multihospital database (Premier). AB - BACKGROUND: Video-assisted thoracic surgical (VATS) lobectomies and wedge resections result in less morbidity and shorter length of stay than resections via thoracotomy. The impact of robot-assisted thoracic surgical (RATS) lobectomy on clinical and economic outcomes has not been examined. This study compared hospital costs and clinical outcomes for VATS lobectomies and wedge resections versus RATS. METHODS: Using the Premier hospital database, patients aged >=18 years with a record of thoracoscopic lobectomy, segmental resection, or excision of a lesion or tissue from the lung between 2009 and 2011 were identified. Procedures using robotic technology were identified if 1 of 2 conditions were met: (1) a robotic International Classification of Diseases, Ninth Revision procedure code or (2) the text fields in the hospital record indicated that the robot was used. Using a propensity score and based on severity and comorbidities, certain demographics and hospital characteristics were matched. The association between VATS or RATS and adverse events, hospital costs, surgery time, and length of stay was examined. RESULTS: Of 15,502 patient records analyzed, 96% (n = 14,837) were performed without robotic assistance. Using robotic assistance was associated with higher average hospital costs per patient. The average cost of inpatient procedures with RATS was $25,040.70 versus $20,476.60 for VATS (P = .0001) for lobectomies and $19,592.40 versus $16,600.10 (P = .0001) for wedge resections, respectively. Inpatient operating times were longer for RATS lobectomy than VATS lobectomy (4.49 hours vs 4.23 hours; P = .0959) and wedge resection (3.26 vs 2.86 hours; P = .0003). Length of stay was similar with no differences in adverse events. CONCLUSIONS: RATS lobectomy and wedge resection seem to have higher hospital costs and longer operating times, without any differences in adverse events. PMID- 24210835 TI - Genotype-oropharyngeal phenotype correlation in Mexican patients with dystrophic epidermolysis bullosa. AB - Previous investigations have attempted to correlate the genotype with the cutaneous phenotype in patients with epidermolysis bullosa (EB), but never with the oropharyngeal phenotype. Seventeen dystrophic EB (DEB) patients were genotyped for COL7A1 gene mutations and divided into five distinct groups. Oropharyngeal disease severity was assessed with the Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score by an oral medicine specialist. The genotype phenotype correlation was calculated by Kruskal-Wallis analysis of variance using the Mann-Whitney test, applying the Bonferroni correction. The most severe oropharyngeal phenotype was found in the group with the 2470insG/3948insT mutation, with a mean disease severity score of 18.50 +/- 2.12; the mildest was found in the 6862del16 mutation group, with a mean disease severity score of 0.57 +/- 1.13. The most significant difference in median score was found in the total score (P = 0.009), followed by tongue (P = 0.02) and upper lip (P = 0.021), but no correlation was found between disease severity and the groups (P>0.005, after Bonferroni correction). Multiple comparisons among the five different genotypic groups revealed no statistically significant genotype-oropharyngeal phenotype correlation; it was not possible to establish which group was more severe, or to associate a specific mutation to a specific oropharyngeal phenotype. PMID- 24210836 TI - Does acute passive stretching increase muscle length in children with cerebral palsy? AB - BACKGROUND: Children with spastic cerebral palsy experience increased muscle stiffness and reduced muscle length, which may prevent elongation of the muscle during stretch. Stretching performed either by the clinician, or children themselves is used as a treatment modality to increase/maintain joint range of motion. It is not clear whether the associated increases in muscle-tendon unit length are due to increases in muscle or tendon length. The purpose was to determine whether alterations in ankle range of motion in response to acute stretching were accompanied by increases in muscle length, and whether any effects would be dependent upon stretch technique. METHODS: Eight children (6-14 y) with cerebral palsy received a passive dorsiflexion stretch for 5 * 20 s to each leg, which was applied by a physiotherapist or the children themselves. Maximum dorsiflexion angle, medial gastrocnemius muscle and fascicle lengths, and Achilles tendon length were calculated at a reference angle of 10 degrees plantarflexion, and at maximum dorsiflexion in the pre- and post-stretch trials. FINDINGS: All variables were significantly greater during pre- and post-stretch trials compared to the resting angle, and were independent of stretch technique. There was an approximate 10 degrees increase in maximum dorsiflexion post stretch, and this was accounted for by elongation of both muscle (0.8 cm) and tendon (1.0 cm). Muscle fascicle length increased significantly (0.6 cm) from pre to post-stretch. INTERPRETATION: The results provide evidence that commonly used stretching techniques can increase overall muscle, and fascicle lengths immediately post-stretch in children with cerebral palsy. PMID- 24210838 TI - What is the value of historical fidelity in restoration? AB - The following considers the role of historical fidelity in habitat reconstruction efforts. To what extent should habitat reconstruction be guided by the goal of recreating some past state of a damaged ecosystem? I consider Sarkar's "replacement argument," which holds that, in most habitat reconstruction efforts, there is little justification for appealing to historical fidelity. I argue that Sarkar does not provide adequate grounds for deprecating historical fidelity relative to other natural values such as biodiversity or wild nature. PMID- 24210837 TI - Relationship of plasma cytokines and clinical biomarkers to memory performance in HIV. AB - Chronic systemic immune activation and inflammatory processes have been linked to brain dysfunction in medically stable HIV-infected people. We investigated the association between verbal memory performance and plasma concentrations of 13 cytokines measured using multiplexed bead array immunoassay in 74 HIV seropositive individuals and 50 HIV-seronegative controls. Memory performance was positively related to levels of IL-8 and IFN-gamma, and negatively related to IL 10 and IL-18 and to hepatitis C infection. Memory performance was not significantly related to HIV disease markers. The results indicate the importance of systemic immune and inflammatory markers to neurocognitive function in chronic and stable HIV disease. PMID- 24210839 TI - Effects of albumin and synthetic polypeptide-coated oxygenators on IL-1, IL-2, IL 6, and IL-10 in open heart surgery. AB - BACKGROUND: In this study, we have tried to demonstrate the effects of coating style used in oxygenators on various hematologic and clinical parameters. MATERIALS AND METHODS: Twenty-seven patients were included in the study, who had undergone operations because of elective coronary artery disease. Albumin-coated oxygenator was used in Group I. In Group II, a synthetic polypeptide-coated oxygenator was used. C1-inhib (complement), C3c, C4, interleukins (IL-1beta, IL2, IL-6, IL-10), and tumor necrosis factor alpha (TNF-alpha) levels were examined at four different time intervals. Hemoglobin, hematocrit, leukocyte and platelet counts, drainage, and transfused blood volumes were analyzed. RESULTS: Albumin levels were significantly lower in Group I than those in Group II 5 minutes after the removal of the cross-clamp. Twenty-four hours after the surgery, Group I patients also had a significantly higher white blood cell count compared to Group II patients. TNF-alpha levels in Group I were always expressed in considerably higher amounts than those in Group II. IL-6 levels were significantly higher in Group I, but IL-10 levels were observed to be higher in Group II (p < 0.05). CONCLUSION: Synthetic polypeptide-coated advanced technology, which employed oxygenators, had an important attenuator effect on acute phase reactants and also on the inflammatory response. PMID- 24210840 TI - Behavioral compliance for dynamic versus static signs in an immersive virtual environment. AB - This study used an immersive virtual environment (IVE) to examine how dynamic features in signage affect behavioral compliance during a work-related task and an emergency egress. Ninety participants performed a work-related task followed by an emergency egress. Compliance with uncued and cued safety signs was assessed prior to an explosion/fire involving egress with exit signs. Although dynamic presentation produced the highest compliance, the difference between dynamic and static presentation was only statistically significant for uncued signs. Uncued signs, both static and dynamic, were effective in changing behavior compared to no/minimal signs. Findings are explained based on sign salience and on task differences. If signs must capture attention while individuals are attending to other tasks, salient (e.g., dynamic) signs are useful in benefiting compliance. This study demonstrates the potential for IVEs to serve as a useful tool in behavioral compliance research. PMID- 24210841 TI - Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. PMID- 24210842 TI - A study to promote breast feeding in the Helsinki Metropolitan area in Finland. AB - OBJECTIVE: the aim of this study was to assess the impact of providing intensified support for breast feeding during the perinatal period. DESIGN: a quasi-experimental design with non-equivalent control group. SETTING: three public maternity hospitals (two study, one control) in the Helsinki Metropolitan area in Finland. PARTICIPANTS: a convenience sample of 705 mothers (431 in the intervention group, 274 in the control group). METHODS AND INTERVENTION: in this study, families in the intervention group had access to intensified breast feeding support from midpregnancy, whereas those in the control group had access to normal care. Intensified support included lectures and workshops to health professionals, and families in the intervention group had access to more intensive support and counselling for breast feeding and a breast feeding outpatient clinic. Additionally, an internet-based intervention was only used in the intervention group, but not in the control group. Mothers in the control group received normal care from the midwifery and nursing professionals who were to continue their work normally. The data were analysed statistically. FINDINGS: altogether 705 women participated in the study. In the intervention group (n=431), 76% of the women breast fed exclusively throughout the hospital stay, compared to 66% of the mothers in the control group (n=274). In multivariate analysis, the likelihood of exclusive breast feeding at the time of responding (at hospital discharge or after that at home) was increased by the mother not being treated for an underlying illness or medical problem during pregnancy, being in the intervention group, having normal vaginal childbirth, high breast feeding confidence, positive attitude towards breast feeding, good coping with breast feeding, and 24-hour presence of the infant's father in the ward. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the low exclusive breast feeding rates of newborns could be increased by using intensified breast feeding support. Mothers' health problems during pregnancy can decrease exclusive breast feeding. Mothers with health problems or other than normal childbirth should receive extra breast feeding support, and the presence of fathers in the ward should be encouraged. Intensified breast feeding counselling and support helps mothers to breast feed exclusively. This support should be available in a variety of forms, so that mothers can choose the type of support they need. As breast feeding counselling and support is intensified, more mothers succeed with exclusive breast feeding. PMID- 24210843 TI - Computer-assisted training of phoneme-grapheme correspondence for children who are deaf and hard of hearing: effects on phonological processing skills. AB - OBJECTIVE: Examine deaf and hard of hearing (DHH) children's phonological processing skills in relation to a reference group of children with normal hearing (NH) at two baselines pre intervention. Study the effects of computer assisted phoneme-grapheme correspondence training in the children. Specifically analyze possible effects on DHH children's phonological processing skills. METHODS: The study included 48 children who participated in a computer-assisted intervention study, which focuses on phoneme-grapheme correspondence. Children were 5, 6, and 7 years of age. There were 32 DHH children using cochlear implants (CI) or hearing aids (HA), or both in combination, and 16 children with NH. The study had a quasi-experimental design with three test occasions separated in time by four weeks; baseline 1 and 2 pre intervention, and 3 post intervention. Children performed tasks measuring lexical access, phonological processing, and letter knowledge. All children were asked to practice ten minutes per day at home supported by their parents. RESULTS: NH children outperformed DHH children on the majority of tasks. All children improved their accuracy in phoneme-grapheme correspondence and output phonology as a function of the computer-assisted intervention. For the whole group of children, and specifically for children with CI, a lower initial phonological composite score was associated with a larger phonological change between baseline 2 and post intervention. Finally, 18 DHH children, whereof 11 children with CI, showed specific intervention effects on their phonological processing skills, and strong effect sizes for their improved accuracy of phoneme-grapheme correspondence. CONCLUSION: For some DHH children phonological processing skills are boosted relatively more by phoneme-grapheme correspondence training. This reflects the reciprocal relationship between phonological change and exposure to and manipulations of letters. PMID- 24210844 TI - A new device for treatment of persistent otitis media with effusion. AB - OBJECTIVES: Most children suffer from otitis media with effusion (OME) before starting school. Insertion of grommets into the eardrum for treatment of OME is one of the most common operations performed in childhood. The efficiency and compliance of treatment with a new non-invasive device was evaluated in children with bilateral OME with disease duration of at least 3 months. METHODS: A device for autoinflation was developed to enable a combined modified Valsalva and Politzer maneuver. Ten children, aged 3-8 years (mean: 5 years and 2 months) with OME tested the device for estimation of its ability to ventilate the middle ear. Another thirty-one children, with persistent bilateral OME for at least three months, were divided into a treatment and a control group. Twenty-one children (42 ears), aged 2-7 year (mean: 4 years and 6 months), participated as the treatment group and ten patients (20 ears), aged 3-7 years (mean: 4 years and 5 months), were included as controls. Tympanometry and otomicroscopy were performed at inclusion and at the end of the study. RESULTS: In the treatment group the middle ear pressure was normalized in 52% and improved in 31% of the ears with 7 children (33%) achieving bilateral and 8 (38%) unilateral normalization. In the control group the middle ear pressure was normalized in 15%, improved in 15% and deteriorated in 10% of the ears with one child (10%) achieving bilateral and one child (10%) unilateral normalization. Statistically significant differences (p < 0.001) were observed in the pressure difference and the tympanometry type changes between the treatment and the control group. Otomicroscopic examination revealed that the number of ears judged as OME was reduced by 62% in the treatment group in comparison with 20% in the control group. All children managed to perform the maneuver and no side effects were neither reported nor detected. CONCLUSIONS: The device was efficient in ventilation of the middle ear with normalization or improvement of the negative middle ear pressure and otomicroscopic findings in young children with persistent OME. PMID- 24210845 TI - Streptococcal superantigens: categorization and clinical associations. AB - Superantigens are key virulence factors in the immunopathogenesis of invasive disease caused by group A streptococcus. These protein exotoxins have also been associated with severe group C and group G streptococcal infections. A number of novel streptococcal superantigens have recently been described with some resulting confusion in their classification. In addition to clarifying the nomenclature of streptococcal superantigens and proposing guidelines for their categorization, this review summarizes the evidence supporting their involvement in various clinical diseases including acute rheumatic fever. PMID- 24210846 TI - Number needed to treat from absolute risk and incidence rate: how to make apples and oranges comparable? PMID- 24210847 TI - Stump infections after major lower-limb amputation: a 10-year retrospective study. AB - BACKGROUND AND PURPOSE: There is little published data on the diagnostic and therapeutic management of lower-limb stump infections (excluding toe and forefoot amputations). PATIENTS AND METHODS: We made a retrospective observational study of 72 patients having undergone a major lower-limb amputation for a vascular or traumatic reason, complicated by post-surgical stump infection, between January 1, 2000 and December 31, 2009. RESULTS: Stump infection was diagnosed more than 6weeks after amputation in half of the patients. Staphylococcus was the most frequently isolated bacterium. Ultrasonography and CT scan combined with fistulography were useful to confirm the diagnosis and to determine the extension of infection. Thirty-two patients (44%) needed surgical revision in addition to antibiotic treatment. Patients diagnosed with bone infection more frequently required complementary surgery than those with soft tissue infection (P<0.001). CONCLUSION: The optimal management of this type of infection requires obtaining reliable bacteriological documentation (abscess aspiration in case of soft tissue infection or bone biopsy in case of osteomyelitis) to adapt to the antibiotic treatment. The management should be multidisciplinary (orthopedic or vascular surgeons, rehabilitation specialists, and infectious diseases physicians). Most patients may use prosthesis once the infection is treated. PMID- 24210848 TI - Evaluation of a subject-specific finite-element model of the equine metacarpophalangeal joint under physiological load. AB - The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal locomotion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle-tendon forces, joint loads and cartilage stresses all increased as locomotion speed increased from walking to trotting and finally cantering. Perturbations to muscle-tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites of common injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation. PMID- 24210850 TI - Walking at the preferred stride frequency maximizes local dynamic stability of knee motion. AB - Healthy humans display a preference for walking at a stride frequency dependent on the inertial properties of their legs. Walking at preferred stride frequency (PSF) is predicted to maximize local dynamic stability, whereby sensitivity to intrinsic perturbations arising from natural variability inherent in biological motion is minimized. Previous studies testing this prediction have employed different variability measures, but none have directly quantified local dynamic stability by computing maximum finite-time Lyapunov exponent (lambda(Max)), which quantifies the rate of divergence of nearby trajectories in state space. Here, ten healthy adults walked 45 m overground while sagittal motion of both knees was recorded via electrogoniometers. An auditory metronome prescribed 7 different frequencies relative to each individual's PSF (PSF; +/-5, +/-10, +/-15 strides/min). Stride frequencies were performed under both freely adopted speed (FS) and controlled speed (CS: set at the speed of PSF trials) conditions. Local dynamic stability was maximal (lambda(Max) was minimal) at the PSF, becoming less stable for higher and lower stride frequencies. This occurred under both FS and CS conditions, although controlling speed further reduced local dynamic stability at non-preferred stride frequencies. In contrast, measures of variability revealed effects of stride frequency and speed conditions that were distinct from lambda(Max). In particular, movement regularity computed by approximate entropy (ApEn) increased for slower walking speeds, appearing to depend on speed rather than stride frequency. The cadence freely adopted by humans has the benefit of maximizing local dynamic stability, which can be interpreted as humans tuning to their resonant frequency of walking. PMID- 24210849 TI - Murine patellar tendon biomechanical properties and regional strain patterns during natural tendon-to-bone healing after acute injury. AB - Tendon-to-bone healing following acute injury is generally poor and often fails to restore normal tendon biomechanical properties. In recent years, the murine patellar tendon (PT) has become an important model system for studying tendon healing and repair due to its genetic tractability and accessible location within the knee. However, the mechanical properties of native murine PT, specifically the regional differences in tissue strains during loading, and the biomechanical outcomes of natural PT-to-bone healing have not been well characterized. Thus, in this study, we analyzed the global biomechanical properties and regional strain patterns of both normal and naturally healing murine PT at three time points (2, 5, and 8 weeks) following acute surgical rupture of the tibial enthesis. Normal murine PT exhibited distinct regional variations in tissue strain, with the insertion region experiencing approximately 2.5 times greater strain than the midsubstance at failure (10.80+/-2.52% vs. 4.11+/-1.40%; mean+/-SEM). Injured tendons showed reduced structural (ultimate load and linear stiffness) and material (ultimate stress and linear modulus) properties compared to both normal and contralateral sham-operated tendons at all healing time points. Injured tendons also displayed increased local strain in the insertion region compared to contralateral shams at both physiologic and failure load levels. 93.3% of injured tendons failed at the tibial insertion, compared to only 60% and 66.7% of normal and sham tendons, respectively. These results indicate that 8 weeks of natural tendon-to-bone healing does not restore normal biomechanical function to the murine PT following injury. PMID- 24210851 TI - Pediatric bed fall computer simulation model: parametric sensitivity analysis. AB - Falls from beds and other household furniture are common scenarios that may result in injury and may also be stated to conceal child abuse. Knowledge of the biomechanics associated with short-distance falls may aid clinicians in distinguishing between abusive and accidental injuries. In this study, a validated bed fall computer simulation model of an anthropomorphic test device representing a 12-month-old child was used to investigate the effect of altering fall environment parameters (fall height, impact surface stiffness, initial force used to initiate the fall) and child surrogate parameters (overall mass, head stiffness, neck stiffness, stiffness for other body segments) on fall dynamics and outcomes related to injury potential. The sensitivity of head and neck injury outcome measures to model parameters was determined. Parameters associated with the greatest sensitivity values (fall height, initiating force, and surrogate mass) altered fall dynamics and impact orientation. This suggests that fall dynamics and impact orientation play a key role in head and neck injury potential. With the exception of surrogate mass, injury outcome measures tended to be more sensitive to changes in environmental parameters (bed height, impact surface stiffness, initiating force) than surrogate parameters (head stiffness, neck stiffness, body segment stiffness). PMID- 24210852 TI - Quantification of finger joint loadings using musculoskeletal modelling clarifies mechanical risk factors of hand osteoarthritis. AB - Owing to limited quantitative data related to the loadings (forces and pressures) acting upon finger joints, several clinical observations regarding mechanical risk factors of hand osteoarthritis remain misunderstood. To improve the knowledge of this pathology, the present study used musculoskeletal modelling to quantify the forces and pressures acting upon hand joints during two grasping tasks. Kinematic and grip force data were recorded during both a pinch and a power grip tasks. Three-dimensional magnetic resonance imaging measurements were conducted to quantify joint contact areas. Using these datasets as input, a musculoskeletal model of the hand and wrist, including twenty-three degrees of freedom and forty-two muscles, has been developed to estimate joint forces and joint pressures. When compared with the power grip task, the pinch grip task resulted in two to eight times higher joint loadings whereas the grip forces exerted on each finger were twice lower. For both tasks, joint forces and pressures increased along a disto-proximal direction for each finger. The quantitative dataset provided by the present hand model clarified two clinical observations about osteoarthritis development which were not fully understood, i.e., the strong risk associated to pinch grip tasks and the high frequency of thumb-base osteoarthritis. PMID- 24210853 TI - Molecular markers of programmed cell death in donor hearts before transplantation. AB - BACKGROUND: In this study we investigate whether pro-apoptotic, pro-inflammatory and other early signaling markers indicative of increased propensity for cell death processes were evident in human donor heart allografts immediately before transplantation, and whether there is an association with primary graft failure. METHODS: A prospective study was performed utilizing donor left atrial myocardium collected at the time of implantation of hearts from brain-dead donors (BDD, n = 29). In addition, to explore the potential of donor hearts from donation after circulatory death (DCD), myocardial samples were obtained during transplantation of lungs from DCD donors (n = 6). A comparator reference group (n = 7) consisted of left atrial specimens from patients undergoing mitral valve surgery. RESULTS: Significantly raised levels of caspase-3 specific activity, activated hypoxia inducible factor-1 (HIF-1alpha) and 8-hydroxy-2'-deoxyguanosine were evident in the transplanted hearts (from BDD) that developed primary graft failure (n = 11). DCD hearts did not differ from BDD with regard to mRNA expression levels of FAS, Bax, IL-6 and caspase-3. Although DCD hearts exhibited lower caspase-3 specific activity and activated hypoxia-inducible factor-1 protein, they had higher levels of mRNA for NF-kappaB, Bnip3 and caspase-1 mRNA. Increased 8-hydroxy-2' deoxyguanosine levels reflected greater oxidative stress and reactive oxygen species-related DNA fragmentation. CONCLUSIONS: Our data indicate a significant role of pro-apoptotic and pro-inflammatory activity in allografts that subsequently exhibit primary graft failure. The relatively lower levels of apoptotic and inflammatory activity in DCD hearts suggest they may represent a potentially usable donor cardiac allograft pool. This possibility requires further detailed molecular and clinical research. PMID- 24210854 TI - Effect of swirling inlet condition on the flow field in a stenosed arterial vessel model. AB - Blood flow in an artery is closely related to atherosclerosis progression. Hemodynamic environments influence platelet activation, aggregation, and rupture of atherosclerotic plaque. The existence of swirling flow components in an artery is frequently observed under in vivo conditions. However, the fluid-dynamic roles of spiral flow are not fully understood to date. In this study, the spiral blood flow effect in an axisymmetric stenosis model was experimentally investigated using particle image velocimetry velocity field measurement technique and streakline flow visualization. Spiral inserts with two different helical pitches (10D and 10/3D) were installed upstream of the stenosis to induce swirling flows. Results show that the spiral flow significantly reduces the length of recirculation flow and provokes early breakout of turbulent transition, but variation of swirling intensity does not induce significant changes of turbulence intensity. The present results about the spiral flow effects through the stenosis will contribute in achieving better understanding of the hemodynamic characteristics of atherosclerosis and in discovering better diagnosis procedures and clinical treatments. PMID- 24210855 TI - Bile and liver metallothionein behavior in copper-exposed fish. AB - The present study analyzed metallothionein (MT) excretion from liver to bile in Nile Tilapia (Oreochromis niloticus) exposed to sub-lethal copper concentrations (2mgL(-1)) in a laboratory setting. MTs in liver and bile were quantified by spectrophotometry after thermal incubation and MT metal-binding profiles were characterized by size exclusion high performance liquid chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS). Results show that liver MT is present in approximately 250-fold higher concentrations than bile MT in non-exposed fish. Differences between the MT profiles from the control and exposed group were observed for both matrices, indicating differential metal-binding behavior when comparing liver and bile MT. This is novel data regarding intra-organ MT comparisons, since differences between organs are usually present only with regard to quantification, not metal-binding behavior. Bile MT showed statistically significant differences between the control and exposed group, while the same did not occur with liver MT. This indicates that MTs synthesized in the liver accumulate more slowly than MTs excreted from liver to bile, since the same fish presented significantly higher MT levels in liver when compared to bile. We postulate that bile, although excreted in the intestine and partially reabsorbed by the same returning to the liver, may also release MT-bound metals more rapidly and efficiently, which may indicate an efficient detoxification route. Thus, we propose that the analysis of bile MTs to observe recent metal exposure may be more adequate than the analysis of liver MTs, since organism responses to metals are more quickly observed in bile, although further studies are necessary. PMID- 24210856 TI - Ultrasound thermal mapping based on a hybrid method combining physical and statistical models. AB - Non-invasive temperature measurement of tissues deep inside the body has great potential for clinical applications, such as temperature monitoring during thermal therapy and early diagnosis of diseases. We developed a novel method for both temperature estimation and thermal mapping that uses ultrasound B-mode radiofrequency data. The proposed method is a hybrid that combines elements of physical and statistical models to achieve higher precision and resolution of temperature variations and distribution. We propose a dimensionless combined index (CI) that combines the echo shift differential and signal intensity difference with a weighting factor relative to the distance from the heat source. In vitro experiments verified that the combined index has a strong linear relationship with temperature variation and can be used to effectively estimate temperature with an average relative error <5%. This algorithm provides an alternative for imaging guidance-based techniques during thermal therapy and could easily be integrated into existing ultrasound systems. PMID- 24210857 TI - 3-D high-frequency ultrasound backscatter analysis of human articular cartilage. AB - High-frequency ultrasound is a promising method for non-invasive characterization of cartilage degeneration. Surface reflection and integrated spectral parameters are often used. In the work described here, human cartilage samples with varying degrees of degeneration were measured using a 40-MHz transducer. Backscatter signals originating from the superficial and transitional zones of cartilage were analyzed using amplitude, spectral and envelope statistical parameters and related to degenerative changes of the matrix given by the Mankin score. The results indicate an increased sensitivity of spectral slope and envelope statistical parameters to early matrix degeneration compared with conventional amplitude parameters. Furthermore, moderate correlations of chondrocyte number with backscatter amplitude and envelope statistics were observed, suggesting that at high frequencies, cells are one important scattering source in cartilage. An application of spectral and envelope statistical parameters to intra-articular ultrasound arthroscopy is conceivable and could improve the diagnostic potential of these examinations. Future studies are necessary to clarify the contributions of chondrocytes, extracellular matrix and collagen content to ultrasound backscatter to further improve the diagnostic potential of ultrasound for cartilage assessment. PMID- 24210858 TI - Muscle ultrasound quantifies segmental neuromuscular outcome in pediatric myelomeningocele. AB - In pediatric spina bifida aperta (SBA), non-invasive assessment of neuromuscular integrity by muscle ultrasound density (MUD) could provide important information about the clinical condition. We therefore aimed to determine the association between pediatric SBA MUD and segmental neurologic function. We included 23 children (age range: 1-18 y) with SBA with L4-5 lesions, and we associated SBA MUD with control values and segmental neuromuscular function. Results revealed that MUD outcomes in the lower extremities: (i) are independent of age, (ii) exceed control values, (iii) differ intra-individually (i.e., between the left and right sides in the same individual) in association with segmental neuromuscular function. We concluded that SBA leg MUD can quantify the segmental neuromuscular condition throughout childhood. PMID- 24210859 TI - Ultra-high frame rate tissue Doppler imaging. AB - We describe a new tissue Doppler imaging (TDI) method, ultra-high frame rate tissue Doppler imaging (UFR-TDI). With two broad transmit beams covering only the ventricular walls, we achieve 1200 frames/s in a four-chamber apical view. We examined 10 healthy volunteers to study the feasibility of this method. Ultra high-frame-rate TDI provided peak annular velocities and time to peak S' intervals in good agreement with those measured with conventional TDI. Moreover, UFR-TDI provided additional information in early and late systole: In all subjects, the method was able to separate the timing of electrical activation, start of mechanical contraction, mitral valve closure and start of ejection. The earliest mechanical activation was seen before mitral valve closure. The method was also able to measure the propagation speed of the mechanical wave created by aortic valve closure. PMID- 24210860 TI - Comparison of diffuse optical tomography, ultrasound elastography and mammography in the diagnosis of breast tumors. AB - Previous studies have reported the usefulness of diffuse optical tomography (DOT), ultrasound elastography (UE) and mammography in differentiating breast tumors. This study was aimed at evaluating and comparing DOT, UE and mammography with respect to their diagnostic performance in differentiating benign and malignant breast tumors. Of the 67 tumors, 45 were histopathologically benign, and 22 were malignant. UE was the most specific (93.33%) of the three diagnostics modalities. DOT and UE were both more accurate (80.60% and 89.55%, respectively) than mammography (63.08%). UE + mammography (93.33% and 91.04%) and DOT + mammography (77.78% and 82.09%) exhibited higher specificity and accuracy, respectively, than mammography alone (57.78% and 63.08%). Receiver operating characteristic (ROC) curves were constructed to assess the performance of the modalities. In conclusion, UE and DOT were superior to conventional mammography in terms of both specificity and accuracy. DOT and UE improve the specificity and accuracy of breast cancer diagnosis, and combining the two modalities improves the diagnostic value. PMID- 24210861 TI - Shear wave elastography assessment of carotid plaque stiffness: in vitro reproducibility study. AB - This study assessed inter- and intra-observer reproducibility of shear wave elastography (SWE) measurements in vessel phantoms simulating soft and hard carotid plaque under steady and pulsatile flow conditions. Supersonic SWE was used to acquire cine-loop data and quantify Young's modulus in cryogel vessel phantoms. Data were acquired by two observers, each performing three repeat measurements. Mean Young's modulus was quantified within 2-mm regions of interest averaged across five frames and, depending on vessel model and observer, ranged from 28 to 240 kPa. The mean inter-frame coefficient of variation (CV) was 0.13 (range: 0.07-0.18) for observer 1 and 0.14 (range: 0.12-0.16) for observer 2, with mean intra-class correlation coefficients (ICCs) of 0.84 and 0.83, respectively. The mean inter-operator CV was 0.13 (range: 0.08-0.20), with a mean ICC of 0.76 (range: 0.69-0.82). Our findings indicate that SWE can quantify Young's modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow. PMID- 24210862 TI - Transverse ultrasound assessment of median nerve deformation and displacement in the human carpal tunnel during wrist movements. AB - The symptoms of carpal tunnel syndrome, a compression neuropathy of the median nerve at the wrist, are aggravated by wrist motion, but the effect of these motions on median nerve motion are unknown. To better understand the biomechanics of the abnormal nerve, it is first necessary to understand normal nerve movement. The purpose of this study was to evaluate the deformation and displacement of the normal median nerve at the proximal carpal tunnel level on transverse ultrasound images during different wrist movements, to have a baseline for comparison with abnormal movements. Dynamic ultrasound images of both wrists of 10 asymptomatic volunteers were obtained during wrist maximal flexion, extension and ulnar deviation. To simplify the analysis, the initial and final shape and position of the median nerve were measured and analyzed. The circularity of the median nerve was significantly increased and the aspect ratio and perimeter were significantly decreased in the final image compared with the first image during wrist flexion with finger extension, wrist flexion with finger flexion and wrist ulnar deviation with finger extension (p < 0.01). There were significant differences in median nerve displacement vector between finger flexion, wrist flexion with finger extension and wrist ulnar deviation with finger extension (all p's < 0.001). The mean amplitudes of median nerve motion in wrist flexion with finger extension (2.36 +/- 0.79 normalized units [NU]), wrist flexion with finger flexion (2.46 +/- 0.84 NU) and wrist ulnar deviation with finger extension (2.86 +/- 0.51 NU) were higher than those in finger flexion (0.82 +/- 0.33 NU), wrist extension with finger extension (0.77 +/- 0.46 NU) and wrist extension with finger flexion (0.81 +/- 0.58 NU) (p < 0.0001). In the normal carpal tunnel, wrist flexion and ulnar deviation could induce significant transverse displacement and deformation of the median nerve. PMID- 24210863 TI - Visualizing tendon elasticity in an ex vivo partial tear model. AB - Supersonic shear imaging (SSI) is evaluated as a means of visualizing changes in regional tendon elasticity caused by partial tears in a porcine model. Thirty digital flexor tendons were cut to 25% (n = 10), 50% (n = 10) and 75% (n = 10) of the tendon thickness along the deep surface. Tendon elasticity was mapped left of, centered on and right of the tear site before and after tearing from 0% to 2% strain. Shear wave speed increased at 1% (p < 0.05) and 2% (p < 0.001) strain for all regions. Deep surface shear wave speed decreased in the 25%, 50% and 75% tears (p < 0.05 and p < 0.001). Computational tendon tear models were also created to investigate regional changes in strain resulting from a tear. In the computational models, strain on the deep surface decreased progressively with increasing tear size. Visualization of tendon shear wave speed was achieved in normal and partially torn tendons, indicating the potential of SSI to add tendon shear wave speed to traditional morphologic assessment of partial tears, which may improve assessment of tendon health. PMID- 24210864 TI - A novel microfluidic chip for assessing dynamic adhesion behavior of cell targeting microbubbles. AB - The primary aim of this study was to develop a microfluidic chip to study the dynamic adhesion behavior of cell-targeted microbubbles. The microfluidic device is composed of polydimethylsiloxane and is fabricated using the soft lithography technique. Each chamber of the microfluidic chip comprises eight U-shaped microsieves, by which various flow velocity distributions are generated. LyP-1 conjugated microbubbles were prepared by coating the surface of the phospholipid shell of microbubbles with LyP-1 peptides via biotin-avidin linkage. Under static conditions, the resulting targeted microbubbles are able to bind onto the surface of cells on incubation with breast cancer cells. Under dynamic fluid conditions, the cell targeting efficiency of the microbubbles was assessed at various flow velocity distributions in a chamber. Accumulation of targeted microbubbles was strongly influenced by flow velocity. Better retention of targeted microbubbles on cell surfaces was achieved at low mean flow velocities (<0.03 cm/s), in agreement with our computer simulation results. In conclusion, our results indicate that the microfluidic system is a useful platform for studying the microbubble-cell adhesive interaction. PMID- 24210865 TI - Doppler vortography: a color Doppler approach to quantification of intraventricular blood flow vortices. AB - We propose a new approach to quantification of intracardiac vorticity based on conventional color Doppler images -Doppler vortography. Doppler vortography relies on the centrosymmetric properties of the vortices. Such properties induce particular symmetries in the Doppler flow data that can be exploited to describe the vortices quantitatively. For this purpose, a kernel filter was developed to derive a parameter, the blood vortex signature (BVS), that allows detection of the main intracardiac vortices and estimation of their core vorticities. The reliability of Doppler vortography was assessed in mock Doppler fields issued from simulations and in vitro data. Doppler vortography was also tested in patients and compared with vector flow mapping by echocardiography. Strong correlations were obtained between Doppler vortography-derived and ground-truth vorticities (in silico: r2 = 0.98, in vitro: r2 = 0.86, in vivo: r2 = 0.89). Our results indicate that Doppler vortography is a potentially promising echocardiographic tool for quantification of vortex flow in the left ventricle. PMID- 24210866 TI - Correlation of virulence genes to clinical manifestations and outcome in patients with Streptococcus dysgalactiae subspecies equisimilis bacteremia. AB - BACKGROUND/PURPOSE: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is increasingly recognized as a human pathogen responsible for invasive infection and streptococcal toxic shock syndrome (STSS). The pathogen possesses virulence genes that resemble those found in Streptococcus pyogenes (GAS). We analyzed the association between these specific toxic genes, clinical presentations, and outcome in patients with SDSE infections. METHODS: Patients (older than 18 years) with community-acquired invasive bacteremia caused by SDSE bacteremia who were undergoing treatment at China Medical University Hospital from June 2007 to December 2010 were included in this study. Multiplex polymerase chain reaction was performed to identify virulence genes of the SDSE isolates. Demographic data, clinical presentations, and outcome in patients with SDSE infections were reviewed and analyzed. RESULTS: Forty patients with 41 episodes of SDSE bacteremia were reviewed. The median age of the patients with SDSE infection was 69.7 years; 55% were female and 78% had underlying diseases. Malignancy (13, 33%) and diabetes mellitus (13, 33%) were the most common comorbidities. The 30-day mortality rate was 12%. Compared with the survivors, the non-survivors had a higher rate of diabetes mellitus (80% vs. 26%), liver cirrhosis (60% vs.11%), shock (60% vs.17%), STSS (60% vs. 8%), and a high Pittsburgh bacteremia score >4 (40% vs. 6%). Most isolates had scpA, ska, saga, and slo genes, whereas speC, speG, speH, speI, speK, smez, and ssa genes were not detected. speA gene was identified only in one patient with STSS (1/6, 17%). All isolates were susceptible to penicillin, cefotaxime, levofloxacin, moxifloxacin, vancomycin, and linezolid. CONCLUSION: In invasive SDSE infections, most isolates carry putative virulence genes, such as scpA, ska, saga, and slo. Clinical SDSE isolates in Taiwan remain susceptible to penicillin cefotaxime, and levofloxacin. PMID- 24210867 TI - Effectiveness of montelukast in pediatric patients with allergic rhinitis. AB - Allergic rhinitis (AR) is one of the most common chronic diseases of childhood and carries significant morbidity as well as physical and psychosocial consequences. Therapy aims to alleviate clinical symptoms, prevent complications and improve psychosocial consequences. Leukotrienes which are amongst the main mediators in pathogenesis of AR have chemotactic properties and lead to increased vascular permeability. Thus, leukotriene antagonism may be an effective therapeutic option in treatment of allergic diseases, specifically AR. Montelukast which is a leukotriene receptor type I inhibitor has variable efficacy in children with AR and the guidelines recommend its use in children with seasonal AR aged six years and above. Although its efficacy is inferior to anti-histamines and intranasal corticosteroids, combination treatment may warrant clinical efficacy. Therefore, montelukast may be considered to be a well tolerated therapeutic option for children with AR with minor side effects though long term results need to be assessed. In conclusion, larger scale research enrolling pediatric cases with seasonal and persistent AR are required before concise recommendations about montelukast use in pediatric AR can be made. PMID- 24210868 TI - A usability evaluation of medical software at an expert conference setting. AB - INTRODUCTION: A usability test was employed to evaluate two medical software applications at an expert conference setting. One software application is a medical diagnostic tool (electrocardiogram [ECG] viewer) and the other is a medical research tool (electrode misplacement simulator [EMS]). These novel applications have yet to be adopted by the healthcare domain, thus, (1) we wanted to determine the potential user acceptance of these applications and (2) we wanted to determine the feasibility of evaluating medical diagnostic and medical research software at a conference setting as opposed to the conventional laboratory setting. METHODS: The medical diagnostic tool (ECG viewer) was evaluated using seven delegates and the medical research tool (EMS) was evaluated using 17 delegates that were recruited at the 2010 International Conference on Computing in Cardiology. Each delegate/participant was required to use the software and undertake a set of predefined tasks during the session breaks at the conference. User interactions with the software were recorded using screen recording software. The 'think-aloud' protocol was also used to elicit verbal feedback from the participants whilst they attempted the pre-defined tasks. Before and after each session, participants completed a pre-test and a post-test questionnaire respectively. RESULTS: The average duration of a usability session at the conference was 34.69 min (SD=10.28). However, taking into account that 10 min was dedicated to the pre-test and post-test questionnaires, the average time dedication to user interaction of the medical software was 24.69 min (SD=10.28). Given we have shown that usability data can be collected at conferences, this paper details the advantages of conference-based usability studies over the laboratory-based approach. For example, given delegates gather at one geographical location, a conference-based usability evaluation facilitates recruitment of a convenient sample of international subject experts. This would otherwise be very expensive to arrange. A conference-based approach also allows for data to be collected over a few days as opposed to months by avoiding administration duties normally involved in laboratory based approach, e.g. mailing invitation letters as part of a recruitment campaign. Following analysis of the user video recordings, 41 (previously unknown) use errors were identified in the advanced ECG viewer and 29 were identified in the EMS application. All use errors were given a consensus severity rating from two independent usability experts. Out of a rating scale of 4 (where 1=cosmetic and 4=critical), the average severity rating for the ECG viewer was 2.24 (SD=1.09) and the average severity rating for the EMS application was 2.34 (SD=0.97). We were also able to extract task completion rates and times from the video recordings to determine the effectiveness of the software applications. For example, six out of seven tasks were completed by all participants when using both applications. This statistic alone suggests both applications already have a high degree of usability. As well as extracting data from the video recordings, we were also able to extract data from the questionnaires. Using a semantic differential scale (where 1=poor and 5=excellent), delegates highly rated the 'responsiveness', 'usefulness', 'learnability' and the 'look and feel' of both applications. CONCLUSION: This study has shown the potential user acceptance and user friendliness of the novel EMS and the ECG viewer applications within the healthcare domain. It has also shown that both medical diagnostic software and medical research software can be evaluated for their usability at an expert conference setting. The primary advantage of a conference-based usability evaluation over a laboratory-based evaluation is the high concentration of experts at one location, which is convenient, less time consuming and less expensive. PMID- 24210869 TI - A haptic pedal for surgery assistance. AB - The research and development of mechatronic aids for surgery is a persistent challenge in the field of robotic surgery. This paper presents a new haptic pedal conceived to assist surgeons in the operating room by transmitting real-time surgical information through the foot. An effective human-robot interaction system for medical practice must exchange appropriate information with the operator as quickly and accurately as possible. Moreover, information must flow through the appropriate sensory modalities for a natural and simple interaction. However, users of current robotic systems might experience cognitive overload and be increasingly overwhelmed by data streams from multiple modalities. A new haptic channel is thus explored to complement and improve existing systems. A preliminary set of experiments has been carried out to evaluate the performance of the proposed system in a virtual surgical drilling task. The results of the experiments show the effectiveness of the haptic pedal in providing surgical information through the foot. PMID- 24210870 TI - Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway. AB - Pro-inflammatory cytokines have been consistently reported to be elevated in schizophrenia patients. However, it is not known whether cytokines influence the presentation of psychotic symptoms. To address this issue, we evaluated the relationship between levels of inflammatory molecules and psychopathological parameters in patients with schizophrenia. We hypothesized that severity of symptoms would correlate with increased levels of inflammatory cytokines. Serum samples from 47 veterans with a diagnosis of schizophrenia and 20 healthy controls were tested for levels of 38 cytokines/chemokines involved in regulation of immune/inflammatory reactions using a Millipore multiplex bead array in a Luminex 100 system. We found significantly increased levels of GRO, MCP-1, MDC, and sCD40L, and significantly decreased levels of IFN-gamma, IL-2, IL-12p70, and IL-17, in schizophrenia patients compared to controls. In addition, we observed positive correlations between levels of cytokines and the Positive and Negative Symptoms Scale (PANSS) scores in subjects with schizophrenia for G-CSF, IL-1beta, IL1ra, IL-3, IL-6, IL-9, IL-10, sCD40L and TNF-beta. Pathway analyses showed these cytokines to be part of the IL17 pathway. Using principal component analyses, we found the factor that included these cytokines and IL-17 to be associated with positive, general and total PANSS scores. These results suggest that alterations in this pathway may play a role in development of psychotic symptoms in schizophrenia. PMID- 24210871 TI - Can P300 distinguish among schizophrenia, schizoaffective and bipolar I disorders? An ERP study of response inhibition. AB - Research utilizing visual event-related brain potentials (ERPs) has demonstrated that reduced P300 amplitude and prolonged latency may qualify as a biological marker (biomarker) for schizophrenia (SZ). We examined P300 characteristics in response inhibition among three putatively distinct psychopathology groups including schizophrenia (SZ), bipolar I disorder (BD) and schizoaffective disorder (SA) in comparison with healthy controls (CT) to determine their electrophysiological distinctiveness. In two separate studies, deficits in response inhibition indexed by the P300 component were investigated using a lateralized Go/NoGo task. We hypothesized that deficits in response inhibition would be present and distinctive among the groups. In both studies, SZ showed response inhibition deficits as measured by P300 when stimuli were presented to the right visual field. In Study 2, delayed cognitive stimulus evaluation was observed in BD as indexed by prolonged P300 latency for NoGo trials. Six selected NoGo P300 variables out of thirty six NoGo P300 variables (18 amplitude, 18 latency) correctly classified SZ (79%), SA (64%) in Study 1 and seven variables selected in Study 2 classified CT (80%), and SZ (61%), BD (67%) and CT (68%) with the accuracy higher than chance level (33%). The findings suggest that distinct P300 features in response inhibition may be biomarkers with the capacity to distinguish BD and SZ, although SA was not clearly distinguishable from SZ and CT. PMID- 24210872 TI - A review of ligand tethered surface engineered carbon nanotubes. AB - Carbon nanotubes (CNTs) have emerged as fascinating materials, exhibiting promising potential in receptor based targeting owing to their unique physicochemical properties (cell membrane penetration, high surface area and drug payload, biocompatibility, easy surface modification, photoluminescence property, and non-immunogenicity etc). The hydrophilicity, a major constrain associated with the first generation of CNTs i.e. pristine CNTs, could be overcome using functionalization techniques. In the last two decades variety of functionalized CNTs (f-CNTs) i.e. oxidized, amidated, acylated, surfactant and biopolymer assisted, and biomolecules modified have been developed and utilized as effective, safe, nano sized, and smart systems to deliver a wide range of bioactives in the biological system. The purpose of this review is to examine the various aspects of conjugation and associated conjugation chemistry of various targeting ligands to CNTs for their respective biomedical applications. The various biomolecules have been easily tethered to CNTs surfaces including proteins and amino acid, enzymes, nucleic acid (DNA and siRNA), aptamers, vitamins, monoclonal antibodies, peptides (NGR, RGD and Aniopep-2) and so on, for targeting purposes. PMID- 24210873 TI - Mechanoregulation of valvular interstitial cell phenotype in the third dimension. AB - A quantitative understanding of the complex interactions between cells, soluble factors, and the biological and mechanical properties of biomaterials is required to guide cell remodeling toward regeneration of healthy tissue rather than fibrocontractive tissue. In the present study, we characterized the combined effects of boundary stiffness and transforming growth factor-beta1 (TGF-beta1) on cell-generated forces and collagen accumulation. We first generated a quantitative map of cell-generated tension in response to these factors by culturing valvular interstitial cells (VICs) within micro-scale fibrin gels between compliant posts (0.15-1.05 nN/nm) in chemically-defined media with TGF beta1 (0-5 ng/mL). The VICs generated 100-3000 nN/cell after one week of culture, and multiple regression modeling demonstrated, for the first time, quantitative interaction (synergy) between these factors in a three-dimensional culture system. We then isolated passive and active components of tension within the micro-tissues and found that cells cultured with high levels of stiffness and TGF beta1 expressed myofibroblast markers and generated substantial residual tension in the matrix yet, surprisingly, were not able to generate additional tension in response to membrane depolarization signifying a state of continual maximal contraction. In contrast, negligible residual tension was stored in the low stiffness and TGF-beta1 groups indicating a lower potential for shrinkage upon release. We then studied if ECM could be generated under the low tension environment and found that TGF-beta1, but not EGF, increased de novo collagen accumulation in both low and high tension environments roughly equally. Combined, these findings suggest that isometric cell force, passive retraction, and collagen production can be tuned by independently altering boundary stiffness and TGF-beta1 concentration. The ability to stimulate matrix production without inducing high active tension will aid in the development of robust tissue engineered heart valves and other connective tissue replacements where minimizing tissue shrinkage upon implantation is critical. PMID- 24210874 TI - Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis. AB - Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on lymphangiogenesis compared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment. PMID- 24210875 TI - Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance. AB - Resistance to single or multiple chemotherapeutic drugs is a major complication in clinical oncology and is one of the most common treatment limitations in patients with reoccurring cancers. Nanoparticle (NP)-based drug delivery systems (DDS's) have been shown to overcome drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. We demonstrate in this work that polyester-based hyperbranched dendritic-linear (HBDL)-based NPs carrying doxorubicin (Dox) can effectively overcome microsomal glutathione transferase 1 (MGST1)-mediated drug resistance in breast cancer cells. Our DDS was much more effective at considerably lower intracellular Dox concentrations (IC50 6.3 MUm vs. 36.3 MUm) and achieved significantly greater reductions in viability and induced higher degrees of apoptosis (31% vs. 14%) compared to the free drug in the resistant cells. Dox-loaded HBDL NPs were found to translocate across the membranes of resistant cells via active endocytic pathways and to be transported to lysosomes, mitochondria, and the endoplasmic reticulum. A significantly lower amount of Dox accumulated in these cytoplasmic compartments in resistant cells treated with free Dox. Moreover, we found that Dox-HBDL significantly decreased the expression of MGST1 and enhanced mitochondria mediated apoptotic cell death compared to free Dox. Dox-HBDL also markedly activated the JNK pathway that contributes to the apoptosis of drug-resistant cells. These results suggest that HBDL NPs can modulate subcellular drug distribution by specific endocytic and trafficking pathways and that this results in drug delivery that alters enzyme levels and cellular signaling pathways and, most importantly, increases the induction of apoptosis. Our findings suggest that by exploiting the cell transport machinery we can optimize the polymeric vehicles for controlled drug release to overcome drug resistance combat drug resistance with much higher efficacy. PMID- 24210876 TI - Relationship between conventional semen characteristics, sperm motility patterns and fertility of Andalusian donkeys (Equus asinus). AB - Sperm quality has an important role in determining fertility. The aims of this study were to compare the conventional sperm parameters, plus the characteristics of the motility patterns of the different sperm subpopulations, of donkey donors with different fertility level, and to determine their relationships to fertility. Thirty ejaculates from 6 Andalusian donkeys were assessed for gel-free volume, pH, sperm concentration, motility and morphology. The fertility of donkeys was classified on the basis of pregnancy rates per cycle, where donkeys with a per cycle pregnancy rate >=60% were considered to be "fertile" (n=3) and those with a per cycle pregnancy rate <40% were categorized to be "sub-fertile" (n=3). Significant differences (P<0.001) between the "fertile" and the "sub fertile" group were found for total and progressive motility, and for straight line velocity. Sperm variables associated (P<0.05) with an increase in percent pregnant per cycle included total motility (r=0.37), progressive motility (r=0.53), curvilinear velocity (r=0.44), straightness (r=0.39), beat cross frequency (r=0.44), and gel-free volume (r=0.53). Four sperm subpopulations (sP) were identified in fresh semen: sP1 (slow and non-progressive spermatozoa, 20%), sP2 (moderately slow but progressive spermatozoa, 71.2%), sP3 (highly active but non-progressive spermatozoa, 2.9%), and sP4 (highly active and progressive spermatozoa, 5.9%). The lowest percentage (3.1%; P<0.001) of sP4 spermatozoa was observed in the "sub-fertile" group. Three of the sperm subpopulations were related (P<0.05) to fertility (sP2, r=0.54; sP3, r=0.45; sP4, r=0.56). In conclusion, we were able to relate the fertility of donkeys with in vitro measures of sperm motility using computer-assisted sperm analysis techniques. PMID- 24210877 TI - The research of nanoparticles as gene vector for tumor gene therapy. AB - With the development of molecular biology, the application of the gene therapy becomes a tendency in the development of oncotherapy. The gene therapy has been acknowledged as the major progress of modern medicine, also a focus in the oncotherapy research. Commonly vectors of the gene therapy mainly include two categories, namely, viral vectors and nonviral vectors. Nanoparticles gene vector of various different kinds of materials, which belong to non-viral carriers. It presents excellent abilities of adsorption, concentration and protection of DNA, which can be attributed as a main reason of the adsorption and operation of nano gene vector on exogenous genes. In this article, we mainly reviewed the recent studies of the characteristics of nanoparticles, characteristics and transport mechanism of nanoparticles as gene vector, the progress on nanoparticles as gene vector in tumor gene therapy. Nano-gene vectors, as new drug and gene carriers, present characteristics such as the controlled-release, targeting, and the improvement of bioavailability. Nanoparticles for cancer imaging and therapy have evolved rapidly during the last decade and it is expected that more and more will become clinical practise. In the near future, as a new nanometer gene delivery vector will be in medical research and treatment play a bigger role. PMID- 24210878 TI - The positive effects of the revised milk and cheese allowances in the special supplemental nutrition program for women, infants, and children. AB - In 2009, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) implemented revisions to the WIC food packages. Milk and cheese allowances were reduced, and whole milk was disallowed for participants older than 23 months. Using a pre-post research design and scanner data from a New England supermarket chain on purchases of WIC households, this article assesses how the new WIC packages affected milk and cheese purchases and saturated fat intake among WIC households in Connecticut and Massachusetts. Milk and cheese volume purchased by 515 WIC households in Connecticut was compared before and after the WIC revisions (2009-2010) using generalized estimating equation models. Analysis for Massachusetts was descriptive. After implementation of the new WIC packages in Connecticut, whole-milk share declined from about 60% to 25% in WIC milk purchases, but remained flat at about 50% for purchases with non-WIC funds. Total milk volume fell by 14.2% (P<0.001), whole milk by half (P<0.001), and WIC eligible cheese by 37.2% (P<0.001). Restrictions on whole milk shifted WIC purchases to reduced-fat milk in Connecticut and low-fat milk in Massachusetts, where reduced-fat milk is not permitted by WIC. The amounts of saturated fat from purchased milk and cheese declined by 85 g/month per WIC household in Connecticut and 107 g/month in Massachusetts. The 2009 WIC revisions led to a substantial decrease in purchases of whole milk and cheese among WIC families in New England. The related reduction in saturated fat intake could have important public health implications. PMID- 24210880 TI - Physical fitness in pre-registration nursing students. AB - BACKGROUND: Nurses are ideally placed to deliver health promotion interventions, including physical fitness, however evidence suggests that nurses themselves are failing to engage in healthy lifestyles; this in turn making them less likely to promote health. It would appear that some nurses are allowing their own values, beliefs and behaviours to hinder this role. We propose these nurses are in breach of the Nursing and Midwifery (NMC) code. Currently nurses self declare their fitness to practice through the NMC, however self-monitoring has been criticized for its lack of reliability. Recruitment of student nurses in the UK does not currently assess physical fitness levels in line with other professionals such as the armed forces, police or fire service. Over half the nursing workforce is now overweight or obese, with alarming levels of inactivity. Physical activity positively correlates with motivation, wellbeing, coping and positive attitude. These attributes in turn impact on employability, retention and absence. This article explores promoting health, focussing on physical activity and discusses innovative ideas to promote physical activity within the nursing Curricula. PMID- 24210879 TI - 320-Row wide volume CT significantly reduces density heterogeneity observed in the descending aorta: comparisons with 64-row helical CT. AB - The aim of this study was to compare density heterogeneity on wide volume (WV) scans with that on helical CT scans. 22 subjects underwent chest CT using 320-WV and 64-helical modes. Density heterogeneity of the descending aorta was evaluated quantitatively and qualitatively. At qualitative assessment, the heterogeneity was judged to be smaller on WV scans than on helical scans (p<0.0001). Mean changes in aortic density between two contiguous slices were 1.64 HU (3.40%) on WV scans and 2.29 HU (5.19%) on helical scans (p<0.0001). CT density of thoracic organs is more homogeneous and reliable on WV scans than on helical scans. PMID- 24210881 TI - Experiencing everyday ethics in context: frontline data collectors perspectives and practices of bioethics. AB - Data collectors play a vital role in producing scientific knowledge. They are also an important component in understanding the practice of bioethics. Yet, very little attention has been given to their everyday experiences or the context in which they are expected to undertake these tasks. This paper argues that while there has been extensive philosophical attention given to 'the what' and 'the why' in bioethics - what action is taken place and why - these should be considered along 'the who' - who are the individuals tasked with bioethics and what can their insights bring to macro-level and abstract discussions of bioethics. This paper will draw on the philosophical theories of Paul Ricoeur which compliments a sociological examination of data collectors experiences and use of their agency coupled with a concern for contextual and institutional factors in which they worked. In emphasising everyday experiences and contexts, I will argue that data collectors' practice of bioethics was shaped by their position at the frontline of face-to-face interactions with medical research participants and community members, alongside their own personal ethical values and motivations. Institutional interpretations of bioethics also imposed certain parameters on their bioethical practice but these were generally peripheral to their sense of obligation and the expectations conferred in witnessing the needs and suffering of those they encountered during their quotidian research duties. This paper will demonstrate that although the principle of autonomy has dominated discussions of bioethics and gaining informed consent seen as a central facet of ethical research by many research institutions, for data collectors this principle was seldom the most important marker of their ethical practice. Instead, data collectors were concerned with remedying the dilemmas they encountered through enacting their own interpretations of justice and beneficence and imposing their own agency on the circumstances they experienced. Their practice of bioethics demonstrates their contribution to the conduct of research and the shortcomings of an over-emphasis on autonomy. PMID- 24210882 TI - Challenging resistance mechanisms to therapies for metastatic melanoma. AB - Melanoma is the most aggressive form of skin cancer and, if spread outside the epidermis, has a dismal prognosis. Before the approval of the anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab and the BRAF inhibitors vemurafenib and dabrafenib, no other agents had demonstrated better results in terms of overall survival than the DNA-methylating compound dacarbazine (or its oral analog temozolomide). However, most patients with metastatic melanoma do not obtain long-lasting clinical benefit from ipilimumab and responses to BRAF inhibitors are short lived. Thus, combination therapies with inhibitors of DNA repair (e.g., poly(ADP-ribose) polymerase [PARP] inhibitors), novel immunomodulators (monoclonal antibodies against programmed death-1 [PD-1] or its ligand PD-L1), targeted therapies (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] kinase [MEK] or phosphatidylinositol 3-kinase [PI3K]/AKT/mammalian target of rapamycin [mTOR] inhibitors) or antiangiogenic agents are currently being investigated to improve the efficacy of antimelanoma therapies. This review discusses the implications of simultaneously targeting key regulators of melanoma cell proliferation/survival and immune responses to counteract resistance. PMID- 24210883 TI - Dendritic cell immunoreceptor: a novel receptor for intravenous immunoglobulin mediates induction of regulatory T cells. AB - BACKGROUND: Intravenous immunoglobulin (IVIg) is a polyclonal IgG preparation with potent immunomodulating properties. Our laboratory demonstrated that IVIg significantly increases numbers of forkhead box protein 3-positive regulatory T (Treg) cells through generation of tolerogenic dendritic cells (DCs) in an allergic airways disease model. OBJECTIVE: We sought to investigate potential receptors on DCs mediating these events. METHODS: C57BL/6 mice were either sensitized to ovalbumin (OVA) intraperitoneally or through adoptive transfer of OVA-primed DCs and then challenged with intranasal OVA. IVIg was fractionated into sialic acid-enriched IVIg (SA-IVIg) and sialic acid-depleted IVIg (non-SA IVIg). Dendritic cell immunoreceptor (DCIR) constructs in CHO cells or on DCs were examined by using fluorescent microscopy and flow cytometry. RESULTS: Administration of SA-IVIg, but not non-SA-IVIg, to OVA-sensitized and OVA challenged mice induced Treg cells and attenuated airway hyperresponsiveness (AHR) and inflammation comparably with IVIg. Bone marrow-derived dendritic cells cultured with SA-IVIg or IVIg adoptively transferred to mice before OVA challenge induced Treg cells and inhibited AHR. IVIg-treated bone marrow-derived dendritic cells from Fcgamma receptor knockout mice inhibited AHR, suggesting IVIg's action was not caused by Fcgamma receptor-mediated events. Fluorescently labeled IVIg or SA-IVIg bound DCs and colocalized specifically to the C-type lectin DCIR. IVIg binding to DCIR induced phosphorylation of Src homology domain 2-containing protein tyrosine phosphatase (SHP) 2 and Src homology domain 2-containing inositol phosphatase 1 (SHIP-1) and internalization of IVIg into DCs. Inhibition of IVIg binding to DCIR by small interfering RNA completely blocked induction of Treg cells. Inhibition of SHP-2 or abrogation of IgG internalization through clatherin inhibitors rendered IVIg ineffective. CONCLUSIONS: IVIg alleviates allergic airways disease through interaction of SA-IgG with DCIR. DCIR is a novel receptor for IVIg, mediating interaction of innate and adaptive immunity in tolerogenic responses. PMID- 24210884 TI - Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma. AB - BACKGROUND: The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma. The functional expression of TRPV1 on airway epithelium has yet to be elucidated. OBJECTIVE: In this study we examined the molecular, functional, and immunohistochemical expression of TRPV1 in asthmatic and healthy airways. METHODS: Bronchial biopsy specimens and bronchial brushings were obtained from healthy volunteers (n = 18), patients with mild-to-moderate asthma (n = 24), and patients with refractory asthma (n = 22). Cultured primary bronchial epithelial cells from patients with mild asthma (n = 4), nonasthmatic coughers (n = 4), and healthy subjects (n = 4) were studied to investigate the functional role of TRPV1. RESULTS: Quantitative immunohistochemistry revealed significantly more TRPV1 expression in asthmatic patients compared with healthy subjects, with the greatest expression in patients with refractory asthma (P = .001). PCR and Western blotting analysis confirmed gene and protein expression of TRPV1 in cultured primary bronchial epithelial cells. Patch-clamp electrophysiology directly confirmed functional TRPV1 expression in all 3 groups. In functional assays the TRPV1 agonist capsaicin induced dose-dependent IL-8 release, which could be blocked by the antagonist capsazepine. Reduction of external pH from 7.4 to 6.4 activated a capsazepine-sensitive outwardly rectifying membrane current. CONCLUSIONS: Functional TRPV1 channels are present in the human airway epithelium and overexpressed in the airways of patients with refractory asthma. These channels might represent a novel therapeutic target for the treatment of uncontrolled asthma. PMID- 24210885 TI - Molecular and phenotypic abnormalities of B lymphocytes in patients with Wiskott Aldrich syndrome. PMID- 24210886 TI - Brain natriuretic peptide at discharge as a predictor of 6-month mortality in acute decompensated heart failure. AB - BACKGROUND: Brain natriuretic peptide (BNP) is well established in detecting acute decompensation of heart failure (ADHF). The role of BNP at discharge in predicting mortality is less established. Accumulating evidence suggests that inflammatory cytokines play an important role in the development of heart failure. We aimed to examine the contribution of BNP, interleukin 6, and procalcitonin to mortality in ADHF. METHODS: A cohort of 33 patients with ADHF was identified between March 2009 and June 2010 at Rambam Health Care Campus, Haifa, Israel. The cohort was followed up for all-cause mortality during 6 months after hospital discharge. Cox proportional hazard model was used to assess the association between BNP, interleukin-6 and procalcitonin and all-cause mortality. RESULTS: As compared to BNP at admission, BNP at discharge was more predictive for all-cause mortality. The area under the curve for BNP at admission and discharge was 0.810 (P=.004) and 0.864 (P=.001) respectively. Eleven patients (33.3%) patients who died during the follow-up period had higher BNP levels, median 2031.4 (IQR, 1173.4-2707.2), than those who survived; median 692.5 (IQR, 309.9-1159.9), (P = .001). On multivariate analysis, BNP remained an independent predictor for 6 month all-cause mortality HR 9.58 (95% CI, 2.0-45.89) for levels above the median compared to lower levels, (P=.005). Albumin, procalcitonin and interleukin 6 were not associated with all-cause mortality. CONCLUSIONS: BNP at discharge is an independent predictor for all-cause mortality in patients with ADHF. Compared with BNP at admission, BNP at discharge has slightly higher predictive accuracy with regard to 6-month all-cause mortality. PMID- 24210887 TI - Association between mean arterial blood gas tension and outcome in cardiac arrest patients treated with therapeutic hypothermia. AB - BACKGROUND: Studies investigating the relationship between blood gas tension and outcome in cardiac arrest survivors have reported conflicting results. This might have resulted from the use of a blood gas value at a single time point and the difference in the proportion of patients treated with therapeutic hypothermia (TH). We investigated the association of the mean blood gas tensions calculated from blood gas values obtained between restoration of spontaneous circulation and end of TH with the outcome in cardiac arrest patients treated with TH. METHODS: This was a retrospective observational study including 213 adult cardiac arrest patients. The cohort was divided into four categories based on the distribution of the mean Pao2 data using quartiles as cut-off values between categories. According to the mean Paco2, the cohort was divided into hypocarbia, normocarbia, and hypercarbia. The primary outcome was in-hospital mortality. RESULTS: In multivariate analysis, the mean Pao2 quartile was not associated with in-hospital mortality, but hypocarbia was significantly associated with increased risk of in hospital mortality (odds ratio 2.522; 95% confidence interval 1.184-5.372; P = .016). We found a V-shaped independent association between the mean Pao2 and poor neurologic outcome at hospital discharge, with the risk of poor neurologic outcome increasing with a descending and ascending Pao2 ranges. CONCLUSION: Mean Pao2 had no independent association with in-hospital mortality whereas hypocarbia was independently associated with in-hospital mortality. We also found a V-shaped independent association between the mean Pao2 and poor neurologic outcome at hospital discharge. PMID- 24210888 TI - Stress-related cardiomyopathy, ventricular dysfunction, artery thrombosis: a hidden pheochromocytoma. AB - Clinical presentation of pheochromocytoma can vary, and it can sometimes mimic other diseases. Some patients with pheochromocytoma may have atypical presentations, such as clinical features consistent with an acute coronary syndrome, that only later suggest a classical picture of stress-related cardiomyopathy. To our best knowledge, pheochromocytoma has been incidentally revealed in a few cases of catecholamine-induced cardiomyopathy and in only 1 case of peripheral arterial thrombosis. This is the first case of pheochromocytoma revealed after left ventricular dysfunction caused by stress related cardiomyopathy associated with inferior limb artery thrombosis in a patient with a complex cardiovascular history. PMID- 24210889 TI - Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines. AB - OBJECTIVE: The latest guidelines both increased the requirements of chest compression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality chest compression. In this study, we investigated the quality of chest compressions during compression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue. METHODS: Eighty-six undergraduate volunteers were randomly assigned to perform CPR according to the 2005 AHA guidelines (AHA 2005) or AHA 2010. After the training course and theoretical examination of basic life support, eight min of compression-only CPR performance was assessed. The quality of chest compressions including rate and depth of compression was analyzed. The rescuer fatigue was evaluated by the changes of heart rate and blood lactate, and rating of perceived exertion. RESULTS: Thirty-nine participants in the AHA 2005 group and 42 participants in the AHA 2010 group completed the study. Significantly greater mean chest compression depth and compression rate were both achieved in the AHA 2010 group than in the AHA 2005 group. And significantly greater rescuer fatigue was observed in the AHA 2010 group. In addition, the female in the AHA 2010 group could perform the compression rate required by the guidelines, however, significantly shallower compression depth and greater rescuer fatigue were observed when compared to the male. CONCLUSIONS: The quality of chest compressions was significantly improved following the 2010 AHA guidelines, however, it's more difficult for the rescuer to meet the guidelines due to the increased fatigue of rescuer. PMID- 24210890 TI - Halogenated phenolic compound determination in plasma and serum by solid phase extraction, dansylation derivatization and liquid chromatography-positive electrospray ionization-tandem quadrupole mass spectrometry. AB - A robust, sensitive and accurate method was developed for the simultaneous determination in plasma and serum of suite a halogenated phenolic compounds (HPCs) for which several are known to persist in the environment and analytically pure standards are available. Namely, 14 congeners of hydroxylated polybrominated diphenyl ethers (OH-PBDEs), six congeners of hydroxylated polychlorinated biphenyls (OH-PCBs), pentachlorophenol, pentabromophenol and the flame retardant tetrabromobisphenol A (TBBPA). Solid phase extraction (SPE) enriched the target compounds and cleaned up the samples as a result of efficient adsorption on a strong anion-exchange solid phase SPE cartridge (Oasis MAX). After final clean-up the HPCs were derivatized with dansyl chloride and analyzed by liquid chromatography-tandem mass spectrometry with electrospray ionization in positive mode (ESI(+)). Chromatographic separation was achieved on a Luna PFP(2) column (2mm*100mm, 3MUm particle size) with mobile phases of water and acetonitrile (both containing 0.1% formic acid). The addition of the dansyl moiety to the HPCs greatly improved analyte sensitivity as the electrospray ionization efficiency was enhanced. Instrument limits of detection (ILODs) for LC-ESI(+)-MS/MS analysis of the HPCs were in the range of 0.01-0.07ng/mL and the method limits of quantification (MLOQs) were in the range of 0.02-0.15ng/g. Recovery efficiencies of the suite of HPCs ranged from 64% to 118% with relative standard deviations from 2% to 12% from fortified bovine serum samples. The method was successfully applied for HPC determination in representative polar bear and snapping turtle plasma samples. PMID- 24210891 TI - High performance liquid chromatography with evaporative light scattering detection for the characterisation of a vesicular delivery system during stability studies. AB - A normal phase high performance liquid chromatography method with evaporative light scattering detection was developed for the simultaneous quantification of the lipid constituents of a non-ionic surfactant vesicle (NIV) delivery system consisting of tetra-ethylene glycol mono n-hexadecyl ether, cholesterol and dicetyl phosphate. An accelerated stability study performed at 25 degrees C/60% relative humidity (RH) and 40 degrees C/75% RH indicated that the NIV were chemically stable. Similar results were observed when stored at 4 degrees C for 469 days. This chromatographic method developed is a sensitive, robust and high throughput analytical technique that offers the potential for rapid quantification of lipids in liposomal and vesicular systems. The results of the chromatographic studies were supported by parallel size and zeta potential measurements. PMID- 24210892 TI - Monolithic graphene fibers for solid-phase microextraction. AB - Monolithic graphene fibers for solid-phase microextraction (SPME) were fabricated through a dimensionally confined hydrothermal strategy and their extraction performance was evaluated. For the fiber fabrication, a glass pipeline was innovatively used as a hydrothermal reactor instead of a Teflon-lined autoclave. Compared with conventional methods for SPME fibers, the proposed strategy can fabricate a uniform graphene fiber as long as several meters or more at a time. Coupled to capillary gas chromatography (GC), the monolithic graphene fibers in a direct-immersion (DI) mode achieved higher extraction efficiencies for aromatics than those for n-alkanes, especially for polycyclic aromatic hydrocarbons (PAHs), thanks to pi-pi stacking interaction and hydrophobic effect. Additionally, the fibers exhibited excellent durability and can be repetitively used more than 160 times without significant loss of extraction performance. As a result, an optimum extraction condition of 40 degrees C for 50min with 20% NaCl (w/w) was finally used for SPME of PAHs in aqueous samples. For the determination of PAHs in water samples, the proposed DI-SPME-GC method exhibited linear range of 0.05-200MUg/L, limits of detection (LOD) of 4.0-50ng/L, relative standard deviation (RSD) less than 9.4% and 12.1% for one fiber and different fibers, respectively, and recoveries of 78.9-115.9%. The proposed method can be used for analysis of PAHs in environmental water samples. PMID- 24210893 TI - Telepulmonology: effect on quality and efficiency of care. AB - BACKGROUND: Interpreting spirometry results has proven challenging in primary care practice, among others potentially leading to under- and misdiagnosis of COPD. In telepulmonology a general practitioner (GP) digitally consults a pulmonologist to support the interpretation of spirometry results. This study assessed the effect of telepulmonology on quality and efficiency of care. METHODS: Quality of care was measured by five indicators, among others the percentage of TelePulmonology Consultations (TPCs) sent by GPs for advice, percentage of those TPCs resulting in a physical referral, and educational effect of telepulmonology as experienced by GPs. Efficiency was defined as the percentage of prevented unnecessary physical referrals of patients to the pulmonologist. RESULTS: Between April 2009 and November 2012 1.958 TPCs were sent by 158 GPs to 32 pulmonologists. Sixty-nine percent of the TPCs were sent for advice. Based on the advice of the pulmonologist 18% of these TPCs led to a physical referral of patients who would not have been referred without telepulmonology. Thirty-one percent of the TPCs were intended to prevent a physical referral, 68% of these actually prevented a physical referral to a pulmonologist. CONCLUSION: The results show telepulmonology can contribute to quality of care by supporting GPs and can additionally prevent unnecessary physical referrals. PMID- 24210894 TI - Targeting and mimicking collagens via triple helical peptide assembly. AB - As the major structural component of the extracellular matrix, collagen plays a crucial role in tissue development and regeneration. Since structural and metabolic abnormalities of collagen are associated with numerous debilitating diseases and pathologic conditions, the ability to target collagens of diseased tissues could lead to new diagnostics and therapeutics. Collagen is also a natural biomaterial widely used in drug delivery and tissue engineering, and construction of synthetic collagen-like materials is gaining interests in the biomaterials community. The unique triple helical structure of collagen has been explored for targeting collagen strands, and for engineering collagen-like functional assemblies and conjugates. This review focuses on the forefront of research activities in the use of the collagen mimetic peptide for both targeting and mimicking collagens via its triple helix mediated strand hybridization and higher order assembly. PMID- 24210895 TI - Mass spectrometric quantification of L-arginine and its pathway related substances in biofluids: the road to maturity. AB - The amino acid L-arginine together with its metabolites and related substances is in the center of many biologically important pathways, especially the urea cycle and the nitric oxide (NO) synthesis. Therefore, the concentrations of these substances in various biological fluids are of great interest as predictive markers for health and disease. Yet, they provide major analytical difficulties as they are very polar in nature and therefore not easily to be separated on standard reversed phase HPLC stationary phases. Furthermore, as endogenous substances, no analyte-free matrix is available, a fact that results in complicated calibration procedures. This review evaluates the analytical literature for the determination of L-arginine, symmetric dimethylarginine, asymmetric dimethylarginine, monomethylarginine, L-citrulline, L-ornithine, L homoarginine, agmatine and dimethylguanidinovaleric acid in biological fluids. Papers are discussed, which were published since 2007 and describe methods applying capillary electrophoresis (CE), gas chromatography (GC), reversed phase HPLC or polar phase HPLC, coupled to mass spectrometric quantification. Nowadays, many carefully developed and validated methods for L-arginine and its related substances are available to the scientific community. The use of stable isotope labeled internal standards enables high precision and accuracy in mass spectrometry-based quantitative analysis. PMID- 24210896 TI - Skeletal stability of bioresorbable fixation in orthognathic surgery: a systemic review. AB - BACKGROUND: Over the past 20 years, there has been an increase in the use of bioresorbable fixation system in orthognathic surgery, but concerns remain about the stability of fixation. This review is to seek evidence for the effectiveness of bioresorbable fixation systems compared to titanium systems used for orthognathic surgery. METHODS: A systematic review of the scientific literature listed on PubMed, Embase, Cochrane Central Register of Systemic Reviews and Cochrane Central Register of Controlled Trials was performed, up to December 2012. RESULTS: Twenty articles were selected based on inclusion and exclusion criteria: five RCTs and fifteen prospective. We compared these studies, published between 1997 and 2012 and involving 1092 participants examining skeletal stability of bioresorbable fixation in orthognathic surgery. CONCLUSION: This review found that the published data have shown that bioresorbable fixation systems produce reliable skeletal stability. PMID- 24210897 TI - The prevalence of chronic health conditions impacting on daily functioning and the association with emotional well-being among a national sample of high school students. AB - PURPOSE: This study aims to describe the prevalence of self-reported chronic health conditions among high school students in New Zealand, the extent to which the condition impacts on their activities and socialization, and to explore the association between the level of impact of the illness or disability and the emotional well-being of students with chronic health conditions. METHODS: A two stage cluster sample of 9,107 students (Years 9-13) from 96 New Zealand high schools participated in a 2007 health survey using internet tablets. Students were asked about any chronic illness or disabilities lasting more than 6 months, the impact of the illness or disabilities on their daily activities and socialization, and their depressive symptoms (RADS-SF) and emotional well-being (WHO-5). RESULTS: Almost one in five students (18%) reported a chronic health condition. Among them, 28% reported an impact of their illness or disability on their activities, and 8% reported an impact on their ability to socialize. High levels of depressive symptoms were found among students with chronic health conditions reporting that their illness or disability impacts their activities (18%) or their ability to socialize (40%), and this was significantly higher than among students without chronic health conditions (10%). CONCLUSIONS: Our findings suggest that there is a large group of adolescents with chronic health conditions for whom their illness or disability has an impact on their daily activities and ability to socialize with their peers. These students are more likely to experience emotional distress and require support and opportunities for healthy youth development. PMID- 24210898 TI - Preventing adolescent alcohol use: effects of a two-year quasi-experimental community intervention intensifying formal and informal control. AB - PURPOSE: To determine the effect on adolescent alcohol use of a community intervention combining intensified formal control (restricting retail supply) and informal control (restricting social supply). Intervention effects on intermediate intervention goals were investigated. Analyses for different age groups were performed. METHODS: A longitudinal quasi-experimental design (baseline at 2008, plus two yearly post-measurements) was used, including one intervention and one matched-comparison community in The Netherlands. We assessed outcomes by observing 1,368 Dutch adolescents aged 13-15 years at baseline. Main dependent variables were weekly drinking status and progression into drunkenness among weekly drinkers. Additional dependent variables were formal control intermediate intervention goals (frequency of alcohol purchases and perceived ease of purchasing alcohol) and informal control intermediate intervention goals (frequency of alcohol-specific rules and parental alcohol supply). RESULTS: Survival analyses showed no significant reduction in the risk of drinking weekly for adolescents in the intervention region; however, the risk of progressing into drunkenness was reduced by 15% (p = .04) for adolescents drinking weekly. No intervention effects on the intermediate intervention goals were found among 14- and 15-year-olds. The intervention had a positive effect on two of four intermediate intervention goals (i.e., parental alcohol supply and alcohol specific rules) among 13-year-olds. CONCLUSIONS: A combined formal and informal community intervention package is associated with a reduced risk of progressing into drunkenness among drinking adolescents. Interventions focusing on discouraging drinking below a certain age might cause a greater increase in the frequency of purchasing alcohol once reaching this age. PMID- 24210899 TI - Adolescent use of the emergency department instead of the primary care provider: who, why, and how urgent? AB - PURPOSE: Adolescents frequently rely on emergency medical care, rather than using primary care providers (PCPs). Our objectives were to characterize a population of adolescents presenting to a large, urban emergency department (ED) and to examine the reasons why they present to the ED, rather than to their PCP's office. METHODS: Adolescents ages 12 to 21 years and their parents/guardians were invited to participate and asked to complete a brief online survey. Demographic data and triage information were collected from electronic medical records. RESULTS: Of 203 participants, 66% (n = 134) had public insurance, and 40% (n = 82) were triaged as nonurgent. Nearly all (93%, n = 189) reported having a PCP or primary clinic. The most common reasons given for presenting to the ED were participant perception of illness requiring immediate care (34%), followed by PCP referral to the ED (21%). Those with public insurance (odds ratio = 4.44; 95% CI 2.01 to 9.81) or no insurance/unknown insurance status (odds ratio = 4.77; 95% CI 1.34 to 17.01) were more likely to be triaged as nonurgent than those with private insurance. CONCLUSIONS: Many adolescents in this study were triaged as nonurgent, with several participants perceiving they were acutely ill requiring immediate physician care. Further analyses revealed that private insurance was significantly associated with urgent triage status. Future studies could educate adolescents and families about appropriate use of the ED or examine PCP offices directly to determine practices for phone triage and ED referrals of adolescents. PMID- 24210900 TI - Sinonasal manifestations of cystic fibrosis: a correlation between genotype and phenotype? AB - BACKGROUND: Patients with Cystic Fibrosis are prone to develop sinonasal disease. Studies in genotype-phenotype correlations for sinonasal disease are scarce and inconclusive. METHODS: In this observational study several aspects of sinonasal disease were investigated in 104 adult patients with CF. In each patient a disease specific quality of life questionnaire (RSOM-31), nasal endoscopy and a CT scan of the paranasal sinuses were performed. Patients were divided into two groups, class I-III mutations and class IV-V mutations, based on their CFTR mutations. RESULTS: The prevalence of rhinosinusitis in adult patients with CF was 63% and the prevalence of nasal polyps 25%. Patients with class I-III mutations had significantly smaller frontal sinuses, sphenoid sinuses, more opacification in the sinonasal area and more often osteitis/neoosteogenesis of the maxillary sinus wall compared to patients with class IV and V mutations. CONCLUSION: These data suggest more severe sinonasal disease in patients with class I-III mutations compared to patients with class IV-V mutations. PMID- 24210901 TI - Manipulating sleep spindles--expanding views on sleep, memory, and disease. AB - Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes. PMID- 24210902 TI - Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. AB - Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-alpha and IL-1beta. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer. PMID- 24210903 TI - Non-invasive prenatal testing for Down syndrome. AB - Prenatal screening and diagnosis of Down syndrome and other major aneuploidies may be transformed following the identification of cell-free fetal DNA in maternal plasma at the end of the last millennium. Next generation sequencing has enabled the development of tests that accurately predict the presence of fetal trisomies by analysis of cell-free DNA in maternal blood from as early as 10 weeks of gestation. These tests are now widely available in the commercial sector but are yet to be implemented in publicly led health services. In this article we discuss the technical, social, and ethical challenges that these new tests bring. PMID- 24210905 TI - Encoding of mixtures in a simple olfactory system. AB - Natural odors are usually mixtures; yet, humans and animals can experience them as unitary percepts. Olfaction also enables stimulus categorization and generalization. We studied how these computations are performed with the responses of 168 locust antennal lobe projection neurons (PNs) to varying mixtures of two monomolecular odors, and of 174 PNs and 209 mushroom body Kenyon cells (KCs) to mixtures of up to eight monomolecular odors. Single-PN responses showed strong hypoadditivity and population trajectories clustered by odor concentration and mixture similarity. KC responses were much sparser on average than those of PNs and often signaled the presence of single components in mixtures. Linear classifiers could read out the responses of both populations in single time bins to perform odor identification, categorization, and generalization. Our results suggest that odor representations in the mushroom body may result from competing optimization constraints to facilitate memorization (sparseness) while enabling identification, classification, and generalization. PMID- 24210904 TI - Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission. AB - Reelin is a glycoprotein that is critical for proper layering of neocortex during development as well as dynamic regulation of glutamatergic postsynaptic signaling in mature synapses. Here, we show that Reelin also acts presynaptically, resulting in robust rapid enhancement of spontaneous neurotransmitter release without affecting properties of evoked neurotransmission. This effect of Reelin requires a modest but significant increase in presynaptic Ca(2+) initiated via ApoER2 signaling. The specificity of Reelin action on spontaneous neurotransmitter release is encoded at the level of vesicular SNARE machinery as it requires VAMP7 and SNAP-25 but not synaptobrevin2, VAMP4, or vti1a. These results uncover a presynaptic regulatory pathway that utilizes the heterogeneity of synaptic vesicle-associated SNAREs and selectively augments action potential independent neurotransmission. PMID- 24210906 TI - Regulation of axon degeneration after injury and in development by the endogenous calpain inhibitor calpastatin. AB - Axon degeneration is widespread both in neurodegenerative disease and in normal neural development, but the molecular pathways regulating these degenerative processes and the extent to which they are distinct or overlapping remain incompletely understood. We report that calpastatin, an inhibitor of calcium activated proteases of the calpain family, functions as a key endogenous regulator of axon degeneration. Calpastatin depletion was observed in degenerating axons after physical injury, and maintaining calpastatin inhibited degeneration of transected axons in vitro and in the optic nerve in vivo. Calpastatin depletion also occurred in a caspase-dependent manner in trophic factor-deprived sensory axons and was required for this in vitro model of developmental degeneration. In vivo, calpastatin regulated the normal pruning of retinal ganglion cell axons in their target field. These findings identify calpastatin as a key checkpoint for axonal survival after injury and during development, and demonstrate downstream convergence of these distinct pathways of axon degeneration. PMID- 24210907 TI - Spike-timing-dependent plasticity in primate corticospinal connections induced during free behavior. AB - Motor learning and functional recovery from brain damage involve changes in the strength of synaptic connections between neurons. Relevant in vivo evidence on the underlying cellular mechanisms remains limited and indirect. We found that the strength of neural connections between motor cortex and spinal cord in monkeys can be modified with an autonomous recurrent neural interface that delivers electrical stimuli in the spinal cord triggered by action potentials of corticospinal cells during free behavior. The activity-dependent stimulation modified the strength of the terminal connections of single corticomotoneuronal cells, consistent with a bidirectional spike-timing-dependent plasticity rule previously derived from in vitro experiments. For some cells, the changes lasted for days after the end of conditioning, but most effects eventually reverted to preconditioning levels. These results provide direct evidence of corticospinal synaptic plasticity in vivo at the level of single neurons induced by normal firing patterns during free behavior. PMID- 24210909 TI - Effects in cattle of genetic variation within the IGF1R gene on the superovulation performance and pregnancy rates after embryo transfer. AB - The insulin-like growth factor 1 receptor (IGF1R) is a membrane glycoprotein mediating most biological actions of IGF1 and IGF2, and has an important effect on ovulation, pre-implantation embryo development and pregnancy rate. The objectives of this study were to detect IGF1R gene polymorphisms of cattle and analyze the relationship with superovulation performance and pregnancy rates after embryo transfer (ET), as well as the hormone concentrations at the day of ET. One reported SNP of IGF1R G404T and a novel SNP of IGF1R G399A were analyzed in 170 Chinese Holstein donor cows and 118 Luxi recipients cattle. Statistical analysis revealed that the G404T mutation was associated (p=0.019) with increased ovulation rate and females with this mutation had enhanced performance in producing transferable embryos. For the polymorphic locus G399A, recipients with g.399 GG and g.399 GA genotypes had greater pregnancy rates after ET than that of g.399 AA genotype. Furthermore, the same tendency was observed that the genotype groups with greater pregnancy rates had greater progesterone and lesser estrogen concentrations, but these did not reach statistical significance. Results of the present study showed, for the first time, that the polymorphism in IGF1R is associated with superovulation traits, and indicated that the IGFIR gene can be used as a potential marker for donor selection. PMID- 24210908 TI - Noncanonical FK506-binding protein BDBT binds DBT to enhance its circadian function and forms foci at night. AB - The kinase DOUBLETIME is a master regulator of the Drosophila circadian clock, yet the mechanisms regulating its activity remain unclear. A proteomic analysis of DOUBLETIME interactors led to the identification of an unstudied protein designated CG17282. RNAi-mediated knockdown of CG17282 produced behavioral arrhythmicity and long periods and high levels of hypophosphorylated nuclear PERIOD and phosphorylated DOUBLETIME. Overexpression of DOUBLETIME in flies suppresses these phenotypes and overexpression of CG17282 in S2 cells enhances DOUBLETIME-dependent PERIOD degradation, indicating that CG17282 stimulates DOUBLETIME's circadian function. In photoreceptors, CG17282 accumulates rhythmically in PERIOD- and DOUBLETIME-dependent cytosolic foci. Finally, structural analyses demonstrated CG17282 is a noncanonical FK506-binding protein with an inactive peptide prolyl-isomerase domain that binds DOUBLETIME and tetratricopeptide repeats that may promote assembly of larger protein complexes. We have named CG17282 BRIDE OF DOUBLETIME and established it as a mediator of DOUBLETIME's effects on PERIOD, most likely in cytosolic foci that regulate PERIOD nuclear accumulation. PMID- 24210910 TI - Effect of cryopreservation and single layer centrifugation on canine sperm DNA fragmentation assessed by the sperm chromatin dispersion test. AB - The aims of this study were: 1) to assess the effect of freezing and thawing on dog sperm DNA fragmentation index (sDFI) using the sperm chromatin dispersion test (SCDt); and 2) to determine whether or not the sperm selection by single layer centrifugation (SLC) using Androcoll-C improves sperm DNA longevity in SLC selected frozen-thawed dog semen samples. Semen samples were collected from 4 dogs using digital manipulation. After collection, ejaculates were pooled and cryopreserved following a standard protocol. Sperm motility and morphology were assessed before freezing and after thawing as a control for the cryopreservation method used. In experiment 1, sDFI was analyzed immediately before freezing and after thawing (baseline values), showing no significant differences between fresh and frozen-thawed semen samples. In experiment 2, frozen-thawed semen samples were processed or not by SLC using Androcoll-C and longevity of DNA were assessed in terms of sDFI after 24h of in vitro incubation at physiological temperature (38 degrees C). The results showed low values of sDFI in SLC-selected semen in comparison to unselected samples. In conclusion, no effect of cryopreservation was observed on baseline values of dog sperm DNA fragmentation. Additionally, SLC selection using Androcoll-C improved longevity of frozen-thawed sperm DNA assessed by the SCDt. PMID- 24210911 TI - Evaluation of prostate-specific antigen response following cessation of abiraterone acetate: is there evidence for a withdrawal syndrome? PMID- 24210912 TI - Comparative study of AdVance and AdVanceXP male slings in a tertiary reference center. PMID- 24210913 TI - Re: Christoph A. Von Klot, Markus A. Kuczyk, Axel S. Merseburger. No androgen withdrawal syndrome for enzalutamide: a report of disease dynamics in the postchemotherapy setting. Eur Urol 2014;65:258-9: Enzalutamide withdrawal syndrome: fact or fiction? PMID- 24210914 TI - Rapid construction of sigmoid bladder augmentation using absorbable staples: long term results and comparison to standard colocystoplasty in children with neurogenic bladder. AB - OBJECTIVE: Absorbable staples facilitate detubularization and reconfiguration of the bowel when performing augmentation colocystoplasty. We compared the outcomes of stapled sigmoid augmentation with standard sutured colocystoplasty. MATERIALS AND METHODS: Between 2003 and 2011, 108 children underwent bladder augmentation at our institution. Colocystoplasty was used in 30 patients (27.8%). Medical charts of children who underwent stapled (n = 8) or sutured (n = 22) sigmoid augmentation were compared with regard to patient demographics and surgical complications, including anastomotic leak and urolithiasis. RESULTS: Eight children with underwent stapled sigmoid colocystoplasty. Average age at surgery was 8 years (range 4-17 years). Time to detubularize and refashion the bowel segment prior to augmentation was consistently under 5 min. Average length of follow-up was 44 months (range 12-80 months). One patient experienced anastomotic leak. Two of eight children (25%) in the stapled anastomosis cohort developed bladder stones. Twenty-two patients underwent standard sigmoid augmentation during the same time period (average age 8.2 years; range 4-16 years). One of 22 (4.5%) experienced anastomotic leak. Seven of 22 (31.8%) developed cystolithiasis. CONCLUSIONS: Complications from stapled sigmoid anastomosis are similar to those from standard colocystoplasty. Use of absorbable staples decreases operating time by avoiding bowel spatulation and suturing, and should be considered in pediatric patients undergoing colocystoplasty. PMID- 24210915 TI - Protective effect of esterified glucomannan on aflatoxin-induced changes in testicular function, sperm quality, and seminal plasma biochemistry in rams. AB - The aim of this study was to determine the effect of aflatoxin (AF) on spermatologic, biochemical, and testis parameters in rams, and the protective efficiency of esterified glucomannan (EG) co-administered with AF. Thirty-two Merino rams (12-14 months old) were used. The experimental design consisted of four dietary treatments. The control group was fed commercial feed. The AF group was fed with commercial feed plus 250 MUg/d of total AF. The EG group received commercial feed plus 2 g/d of EG. The AF + EG group was given commercial feed plus 250 MUg/d of total AF and 2 g/d of EG. There were treatment, time, and treatment-by-time interaction effects on sperm motility, abnormal spermatozoa, damaged acrosome, and dead spermatozoa (P < 0.01). The percentage of motile sperm was lower and the percentages of abnormal sperm, sperm with damaged acrosomes, and dead sperm were greater in the AF group than in the control, AF+EG, and EG groups, as from week 3 until the end of week 12 (P < 0.05). As from week 3, hyaluronidase activity in the seminal plasma increased significantly in the AF group, compared with the control. The co-administration of AF+EG was found to be effective in preventing the increase in hyaluronidase activity. As week 4, malondialdehyde (MDA) levels were significantly higher in the AF group compared with the control. The combined administration of AF+EG was found to be effective in lowering the MDA levels, increased by AF, to the levels measured in the control (P < 0.05). Although glutathione (GSH) levels were determined to have significantly decreased in the AF group in comparison to the control, it was observed that, in the group co-administered with AF and EG, particularly after week 7, the GSH levels, which had decreased owing to AF, were largely ameliorated (P < 0.05). In conclusion, AF adversely affected spermatologic, biochemical, and testis parameters, and the combined administration of EG with AF reversibly eliminated these adverse effects in rams. PMID- 24210916 TI - Cryogenic changes in proteases and antiprotease activities of buffalo (Bubalus bubalis) and cattle (Bos taurus) semen. AB - The postthaw motility and fertility of buffalo and cattle semen is reduced when they are cryopreserved for artificial insemination. In the present study, an attempt was made to characterize the cryogenic changes in proteases and antiprotease activities (APA) of buffalo and cattle semen because these proteolysis regulators have been reported to be associated with sperm motility and fertility. Buffalo sperm demonstrated at least two major proteases of 45 and 42 kDa and three minor proteases of 95, 52, and 33 kDa. Similarly, cattle sperm demonstrated three major proteases of 62, 45, and 42 kDa and two minor proteases of 85 and 78 kDa. Buffalo seminal plasma demonstrated at least three major proteases of 78, 68, and 62 kDa and one minor protease of 98 kDa and cattle seminal plasma demonstrated one major protease of 68 kDa and two minor proteases of 78 and 75 kDa. Except for the 45 kDa protease, most of the previously mentioned proteases were found to be metalloproteinases. Compared with fresh sperm, cryopreserved buffalo and cattle sperm demonstrated a major protease band of 52/49 kDa and the activity of this protease reduced progressively with the duration of cryopreservation. On the contrary, compared with the fresh seminal plasma, cryopreserved buffalo and cattle semen extenders displayed the presence of a new protease band of 45 kDa and demonstrated that this protease activity was leaked from buffalo and cattle cryopreserved spermatozoa. Buffalo and cattle seminal plasmas displayed at least two major APA of 86 and 26 kDa. Compared with buffalo, cattle seminal plasma demonstrated significantly greater APA. Thus, the present study demonstrated the presence of an array of proteases and APA in buffalo and cattle semen and the activities of which changed during cryopreservation. The leakage of the specific protease activity and changes in the proteases and APA might be attributed to reduced motility and fertility of cryopreserved semen in these species. PMID- 24210917 TI - Risky sexual behaviors: The role of ethnic identity in HIV risk in migrant workers. AB - Migrant workers have been shown to be at a heightened level of risk for HIV, and ethnic identity has been posited to have an impact on engagement in risky sexual behaviors. Our longitudinal study examined associations between baseline and short-term changes in ethnic identity and high-risk sexual behaviors. Baseline (n = 431) and 6-month assessment (n = 270) data were obtained from a larger HIV prevention study conducted among African American and Hispanic migrant workers. Repeated-measures multivariate analysis of covariance and multiple linear regressions were used. Ethnic identity explore, a subscale of ethnic identity, was a significant predictor of overall sexual risk [F(8, 422) = 6.953, p < .001] and unprotected vaginal acts [F(8, 422) = 8.444, p < .001] at baseline. However, ethnic identity had no bearing on changes in risky sexual behaviors. Ethnic identity explore was associated with safer sexual behaviors. PMID- 24210918 TI - Transcriptome surveillance by selective termination of noncoding RNA synthesis. AB - Pervasive transcription of eukaryotic genomes stems to a large extent from bidirectional promoters that synthesize mRNA and divergent noncoding RNA (ncRNA). Here, we show that ncRNA transcription in the yeast S. cerevisiae is globally restricted by early termination that relies on the essential RNA-binding factor Nrd1. Depletion of Nrd1 from the nucleus results in 1,526 Nrd1-unterminated transcripts (NUTs) that originate from nucleosome-depleted regions (NDRs) and can deregulate mRNA synthesis by antisense repression and transcription interference. Transcriptome-wide Nrd1-binding maps reveal divergent NUTs at most promoters and antisense NUTs in most 3' regions of genes. Nrd1 and its partner Nab3 preferentially bind RNA motifs that are depleted in mRNAs and enriched in ncRNAs and some mRNAs whose synthesis is controlled by transcription attenuation. These results define a global mechanism for transcriptome surveillance that selectively terminates ncRNA synthesis to provide promoter directionality and to suppress antisense transcription. PMID- 24210919 TI - Mtr4-like protein coordinates nuclear RNA processing for heterochromatin assembly and for telomere maintenance. AB - The regulation of protein-coding and noncoding RNAs is linked to nuclear processes, including chromatin modifications and gene silencing. However, the mechanisms that distinguish RNAs and mediate their functions are poorly understood. We describe a nuclear RNA-processing network in fission yeast with a core module comprising the Mtr4-like protein, Mtl1, and the zinc-finger protein, Red1. The Mtl1-Red1 core promotes degradation of mRNAs and noncoding RNAs and associates with different proteins to assemble heterochromatin via distinct mechanisms. Mtl1 also forms Red1-independent interactions with evolutionarily conserved proteins named Nrl1 and Ctr1, which associate with splicing factors. Whereas Nrl1 targets transcripts with cryptic introns to form heterochromatin at developmental genes and retrotransposons, Ctr1 functions in processing intron containing telomerase RNA. Together with our discovery of widespread cryptic introns, including in noncoding RNAs, these findings reveal unique cellular strategies for recognizing regulatory RNAs and coordinating their functions in response to developmental and environmental cues. PMID- 24210920 TI - Merits of usability testing for PACS selection. AB - OBJECTIVES: To compare the usability of different Picture Archiving and Communication System (PACS) workstations, determine whether a usability test has added value with respect to the traditional way of comparing PACSs based on functional requirements, and to evaluate the appropriateness of a task-based methodology for a PACS usability test. METHODS: A task-based usability test of four PACS workstations was performed. Radiologists' subjective responses to the PACSs and their performance on the tasks were measured. To mimic the traditional PACS selection process, two functional requirements were defined which the PACSs met in varying degrees. The focus of the usability test was on the aspects of the PACS related to these requirements. The usability results were compared to the PACSs' ability to meet the functional requirements. RESULTS: One PACS outperformed the other PACSs both in terms of subjective preference and task performance, indicating its superior usability. There were differences in usability between PACSs with identical functionality. Also, a PACS with theoretically advantageous functionality for a given task did not necessarily have better usability for this task than a PACS without this functionality. There was a discrepancy between participants' subjective preferences and their task performance, which indicates that it is vital to include performance measures in the usability assessment so that it accurately reflects the efficiency of interaction. CONCLUSIONS: The differences in usability between PACSs with identical functionality indicate that functional requirements alone are insufficient to determine a PACS's overall quality. A usability test should therefore be used in addition to a functional requirement list in a PACS selection process to ensure that a hospital buys the PACS with the highest quality. A task-based usability evaluation methodology, which yields both subjective preference data and objective performance data of radiologists interacting with the PACS, is very suitable for such a usability test. PMID- 24210921 TI - Thermal and electron stimulated luminescence of natural bones, commercial hydroxyapatite and collagen. AB - The luminescence (cathodoluminescence and thermoluminescence) properties of natural bones (Siberian mammoth and adult elephant), commercial hydroxyapatite and collagen were analyzed. Chemical analyses of the natural bones were determined using by Electron Probe Micro-Analysis (EMPA). Structural, molecular and thermal characteristics were determined by X-ray Diffraction (XRD), Raman spectroscopy and Differential Thermal and Thermogravimetric analysis (DTA-TG). Cathodoluminescence (CL) spectra of natural bones and collagen showed similar intense broad bands at 440 and 490 nm related to luminescence of the tetrahedral anion [Formula: see text] or structural defects. A weaker luminescence exhibited at 310 nm could be attributed to small amount of rare earth elements (REEs). Four luminescent bands at 378, 424, 468 and 576 nm were observed in the commercial hydroxyapatite (HAP). Both natural bones and collagen samples exhibited natural thermoluminescence (NTL) with well-defined glow curves whereas that the induced thermoluminescence (ITL) only appears in the samples of commercial hydroxyapatite and collagen. Additional explanations for the TL anomalous fading of apatite, as a crucial difficulty performing dosimetry and dating, are also considered. PMID- 24210922 TI - The burden of childhood asthma and late preterm and early term births. AB - OBJECTIVE: To evaluate the association between gestational age at birth and the risk of subsequent development of asthma. STUDY DESIGN: We conducted a retrospective observational hospital-based birth case-control study in a university-based obstetrics and gynecology department in Finland. A total of 44,173 women delivering between 1989 and 2008 were linked with the social insurance register to identify asthma reimbursements for their offspring (n = 2661). Pregnancy factors were recorded during pregnancy. Infants were categorized as moderately preterm (<= 32 weeks), late preterm (33-36 weeks), early term (37 38 weeks), term (39-40 weeks), or late term and postterm (>= 41 weeks). The main outcome measure was asthma among the infants. RESULTS: Children born moderately preterm (<= 32 weeks gestation) had a significantly increased risk of asthma (aOR, 3.9; 95% CI, 3.2-4.8). The risk of asthma was also increased in those born late preterm (aOR, 1.7; 95% CI, 1.4-2.0) and early term (aOR, 1.2; 95% CI, 1.1 1.4). In contrast, delivery at 41 weeks or later seemed to decrease the risk of asthma (aOR, 0.9; 95% CI, 0.8-1.0). The burden of asthma associated with preterm birth was associated mainly with early term infants, in whom 108 extra cases of asthma were observed. CONCLUSION: Even though the individual risk of asthma was inversely correlated with gestational age at birth, the overall burden brought about by delivery before term was associated with late preterm and early term deliveries. Furthermore, delivery after term was protective against asthma. PMID- 24210924 TI - Improving recognition of cardiovascular risk in children. PMID- 24210926 TI - Cutaneous clues: a genetic disorder diagnosed by dermatologic findings. PMID- 24210925 TI - Hypothermia and early neonatal mortality in preterm infants. AB - OBJECTIVE: To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. STUDY DESIGN: This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 degrees C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. RESULTS: Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 degrees C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 degrees C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 degrees C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08 2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). CONCLUSION: Simple interventions, such as maintaining DR temperature >25 degrees C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival. PMID- 24210927 TI - Brain magnetic resonance imaging in infants with surgical necrotizing enterocolitis or spontaneous intestinal perforation versus medical necrotizing enterocolitis. AB - Magnetic resonance imaging of the brain was performed in 26 preterm infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation at term equivalent age. Infants with surgical NEC or spontaneous intestinal perforation had significantly more brain injury on magnetic resonance imaging compared with infants with medical NEC, even after adjustment for confounders. PMID- 24210928 TI - Light sleep versus slow wave sleep in memory consolidation: a question of global versus local processes? AB - Sleep is strongly involved in memory consolidation, but its role remains unclear. 'Sleep replay', the active potentiation of relevant synaptic connections via reactivation of patterns of network activity that occurred during previous experience, has received considerable attention. Alternatively, sleep has been suggested to regulate synaptic weights homeostatically and nonspecifically, thereby improving the signal:noise ratio of memory traces. Here, we reconcile these theories by highlighting the distinction between light and deep nonrapid eye movement (NREM) sleep. Specifically, we draw on recent studies to suggest a link between light NREM and active potentiation, and between deep NREM and homeostatic regulation. This framework could serve as a key for interpreting the physiology of sleep stages and reconciling inconsistencies in terminology in this field. PMID- 24210923 TI - Variation in feeding practices following the Norwood procedure. AB - OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II. STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed. RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only (n = 57). There was significant variation in feeding mode among sites (oral only 0%-81% and G-tube only 0%-56%, P < .01). After adjusting for site, multivariable modeling showed G-tube feeding at discharge was associated with longer hospitalization, and N-tube feeding was associated with greater number of discharge medications (R(2) = 0.65, P < .01). After adjusting for site, mean pre-stage II weight-for-age z-score was significantly higher in the oral-only group (-1.4) vs the N-tube-only (-2.2) and G-tube-only (-2.1) groups (P = .04 and .02, respectively). CONCLUSIONS: Feeding mode at hospital discharge after the Norwood procedure varied among sites. Prolonged hospitalization and greater number of medications at the time of discharge were associated with tube feeding. Infants exclusively fed orally had a higher weight-for-age z score pre-stage II than those fed exclusively by tube. Exploring strategies to prevent morbidities and promote oral feeding in this highest risk population is warranted. PMID- 24210929 TI - Office-based endovascular suite is safe for most procedures. AB - OBJECTIVE: This study was conducted to identify the safety of endovascular procedures in the office endovascular suite and to assess patient satisfaction in this setting. METHODS: Between May 22, 2007, and December 31, 2012, 2822 patients underwent 6458 percutaneous procedures in an office-based endovascular suite. Demographics of the patients, complications, hospital transfers, and 30-day mortality were documented in a prospective manner. Follow-up calls were made, and a satisfaction survey was conducted. Almost all dialysis procedures were done under local anesthesia and peripheral arterial procedures under conscious sedation. All patients, except those undergoing catheter removals, received hydrocodone and acetaminophen (5/325 mg), diazepam (5-10 mg), and one dose of an oral antibiotic preprocedure and three doses postprocedure. Patients who required conscious sedation received fentanyl and midazolam. Conscious sedation was used almost exclusively in patients having an arterial procedure. Measurements of blood urea nitrogen, creatinine, international normalized ratio, and partial thromboplastin time were performed before peripheral arteriograms. All other patients had no preoperative laboratory tests. Patients considered high risk (American Society of Anesthesiologists Physical Status Classification 4), those who could not tolerate the procedure with mild to moderate conscious sedation, patients with a previous bad experience, or patients who weighed >400 pounds were not candidates for office based procedures. RESULTS: There were 54 total complications (0.8%): venous, 2.2%; aortogram without interventions, 1%; aortogram with interventions, 2.7%; fistulogram, 0.5%; catheters, 0.3%; and venous filter-related, 2%. Twenty-six patients required hospital transfer from the office. Ten patients needed an operative intervention because of a complication. No procedure-related deaths occurred. There were 18 deaths in a 30 day period. Of patients surveyed, 99% indicated that they would come back to the office for needed procedures. CONCLUSIONS: When appropriately screened, almost all peripheral interventions can be performed in the office with minimal complications. For dialysis patients, outpatient intervention has a very low complication rate and is the mainstay of treatment to keep the dialysis access patent. Venous insufficiency, when managed in the office setting, also has a low complication rate. Office-based procedural settings should be seriously considered for percutaneous interventions for arterial, venous, and dialysis related procedures. PMID- 24210930 TI - Inflammation is more distinct in temporomandibular joint osteoarthritis compared to the knee joint. AB - PURPOSE: Most of the current understanding of articular cartilage maintenance and degradation is derived from large load-bearing synovial joints, in particular the knee joint. The aim of this study was to identify valuable degradation markers for cartilage degradation in the temporomandibular joint (TMJ) by comparing the relative concentrations of carboxyterminal telopeptides of collagen types I and II (CTX-I and CTX-II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in synovial fluid (SF) of TMJ and knee joints with cartilage degradation. MATERIALS AND METHODS: In this cross-sectional comparative study, participants were recruited from the University Medical Center Groningen, The Netherlands. Patients with TMJ osteoarthritis were compared with patients with knee osteoarthritis. The outcome variables were the relative SF concentrations of CTX-I, CTX-II, COMP, and PGE2. An independent samples Mann Whitney U test was used to compare the relative concentrations. RESULTS: Thirty consecutive patients (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) with TMJ osteoarthritis and 31 consecutive patients (20 male, 11 female; mean age, 37.4 yr; standard deviation, 13.7 yr) who were scheduled for arthroscopy of the knee joint participated in this study. Significant differences were found between relative concentrations of COMP (P = .000) and PGE2 (P = .005), and no significant differences were found between relative concentrations of CTX-I (P = .720) and CTX-II (P = .242). CONCLUSIONS: Relative SF concentrations of COMP and PGE2 showed significant differences between the TMJ and the knee joint, suggesting that there are differences in pathophysiology and that the inflammatory component may be more distinct in the TMJ. PMID- 24210932 TI - [Cicatricial lesions in Vogt-Koyanagi-Harada syndrome]. PMID- 24210931 TI - [Treatment of high myopic choroidal neovascularisation with intravitreal bevacizumab]. AB - PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (IVB) in the treatment of high myopic choroidal neovascularization (CNV). MATERIALS AND METHODS: Retrospective study of 16 eyes of 16 patients with high myopic choroidal neovascularization treated with first-line IVB (1.25mg/0.05mL) with a one-year follow-up. All patients underwent a complete baseline (M0) ophthalmologic examination, including the measurement of best corrected visual acuity (BCVA), biomicroscopic and fundus examination, fluorescein and indocyanine green angiography, and optical coherence tomography. Patients were followed monthly. Additional IVB was administered when persistent or additional retinal exudation was observed. The main study parameters were visual acuity at 1, 6 and 12 months and the progression of exudation on OCT and angiography. RESULTS: Mean age was 63+/-14 years and spherical equivalent was -15.4+/-7.4 diopters. Baseline BCVA was 0.75+/-0.5 logMAR. Mean follow-up was 15+/-2 months. The average number of IVB was 2.4+/-1.2 injections. Metamorphopsia decreased in all patients and completely disappeared in fourteen eyes. Mean BCVA was 0.5+/-0.3 logMAR at M1 and 0.6+/-0.5 logMAR at M6 and M12. No adverse events related to the intravitreal injections were observed. CONCLUSION: Our study showed that IVB (Avastin((r))) is effective in the treatment of high myopic CNV. Moreover, only a small number of intravitreal injections were required to treat this condition. PMID- 24210933 TI - [Post-traumatic retinal pigment epithelial detachment]. PMID- 24210934 TI - [Anatomical and functional prognosis of secondary retinal detachments after sutureless macular surgery]. AB - PURPOSE: To evaluate the incidence, characteristics and risk factors for rhegmatogenous complications of transconjunctival sutureless 23-gauge vitrectomy (TSV) in macular surgery. The results were correlated with those reported in the literature. METHODS: Multicentric retrospective study of a cohort of patients undergoing macular surgery by 23-gauge TSV between January 2009 and June 2010. RESULTS: Four hundred and seventy-four patients divided into: epiretinal membrane (MEM) (n=279), vitreomacular traction (n=65) and idiopathic macular hole n=130. Forty-three percent of patients were pseudophakic. Posterior vitreous detachment (PVD) was absent in 60% of cases and was therefore systematically performed intraoperatively. It was seen that 1.7% of patients developed retinal tears and 2.7% retinal detachment with a higher incidence in the vitreomacular traction (VMT) group and the group in which the PVD was performed intraoperatively. Rhegmatogenous lesions were localized mainly in the inferior retina in the macular hole group. DISCUSSION: Results are consistent with the TSV literature. Their location does not appear to be related to the sclerotomies or handedness as in 20-gauge surgery, probably due to sclerotomy trocars. Localization of rhegmatogenous lesions in the inferior retina in macular hole surgery suggests a role of gas in this subgroup. In addition to instrument-retinal touch, the performance of a surgical PVD represents a major independent risk factor for retinal detachment (RD). CONCLUSION: Even with limited macular surgery, it is essential to check the retinal periphery for 360 degrees, especially for VMT and intraoperative PVD, and especially inferiorly in the case of gas tamponnade. PMID- 24210935 TI - [Optical quality after 2.2mm microincisional cataract surgery with bimanual I/A in 154 eyes]. AB - PURPOSE: A prospective study to analyze the effects of 2.2mm microincisional coaxial phacoemulsification with bimanual irrigation/aspiration on the optical quality of the cornea and whole eye. METHODS: We compare two groups. Group A: 102 consecutive eyes undergoing this three-incision procedure and implanted with an Alcon(r) SN60WF IQ aspheric intraocular lens. Astigmatism, corneal and total asphericity, as well as H/B ratio were measured by OPD scann II, Nidek(r), Japan, preoperatively (Day 0), 15 days postoperatively (Day 15) and 1 month postoperatively (M1). Group B: 52 eyes with corneal astigmatism greater than 1.25D, undergoing the same procedure but implanted with a Toric IOL (Alcon(r) Toric IQ SN6AT), followed in the same manner but with additional follow-up at 1 year. RESULTS: Corneal surgically induced astigmatism (SIA) was essentially neutral: 0.065D +/- 0.86 at Day 30 in group A, and 0.06D +/- 0.34 at 1 month and 0.008D +/- 0.4 at 12 months in group B. Corneal topographic astigmatism underwent a mean axis shift of 29.95 degrees +/- 27.6 in group A compared to 5.3 degrees +/- 3.7 in Group B, and remained stable at 1 year. Corneal asphericity did not change significantly between Day 0 and 30 in either group. H/B ratio increased significantly in both groups, with a gain of 22 % to 24 % after surgery. CONCLUSIONS: This three-incision procedure does not degrade the optical quality of the cornea. Postoperative shift in the axis of astigmatism is only an issue in cases of low or asymmetric astigmatism and must be kept in mind for low-power toric IOL implantation. PMID- 24210936 TI - [Results of natural hydroxyapatite implants covered with Vicryl(r) mesh in a series of 704 enucleations]. AB - PURPOSE: Retrospective study of local tolerability of a natural hydroxyapatite orbital implant wrapped with Vicryl((r)) (polyglactin) mesh in patients undergoing enucleation. METHOD: Complications were classified into four types according to their management: type 1 if no reoperation was required, type 2 if additional surgery without grafting was required, type 3 if an oral mucosal graft was performed (major dehiscence) and type 4 if the complication required removal of the implant. RESULTS: Seven hundred and four patients with a median follow-up of 44 months. Five hundred and three patients were enucleated as a primary procedure and 201 after failure of conservative management. The overall complication rate was 12.07% (85 patients) with 68 type 1 complications, nine type 2 complications, three type 3 complications and five type 4 complications (0.71%). A total of 17 patients (2.42%) required additional surgery. The use of chemotherapy or radiotherapy before or after surgery did not influence the results. In univariate analysis, the tolerability was better in children than in adults. With multivariate analysis, only the diameter of the implant was an independent risk factor for complications (P=0.001). CONCLUSION: Use of a Vicryl((r)) mesh-wrapped natural hydroxyapatite orbital implant after enucleation is particularly well tolerated including the pediatric population. A compromise should be sought with an implant large enough for good cosmetic results but small enough to avoid complications. PMID- 24210937 TI - [Unpigmented conjunctival melanoma]. PMID- 24210938 TI - [An atypical case of cat scratch disease (Bartonellosis)]. PMID- 24210939 TI - [Central retinal artery occlusion by fat embolism in a young male]. PMID- 24210940 TI - [Superselective intra-arterial chemotherapy with melphalan for retinoblastoma]. PMID- 24210941 TI - Chromatographic techniques coupled with mass spectrometry for the determination of organic acids in the study of autism. AB - Chromatographic methods find application in the diagnostics and prognosis of diseases. They are used in finding new biomarkers, which may result in early medical intervention. Early diagnosis and intervention are especially important in the case of diseases of unknown etiology. One of these is autism. Autism is a neurodevelopmental disorder characterized by severe impairment in reciprocal social interaction and communication and a pattern of repetitive or stereotyped behavior. Organic acids are intermediate metabolites of all major groups of organic cellular components and can play a role in the pathogenesis of autism. This review presents information about abnormal levels of some organic acids observed in the urine of children with autism and determination of acids with the use of chromatographic techniques. 342 literature sources on frequency (2005 2012) of the use of chromatographic methods in the determination of organic compounds in various body fluids were searched. PMID- 24210942 TI - The social brain: neurobiological basis of affiliative behaviours and psychological well-being. AB - The social brain hypothesis proposes that the demands of the social environment provided the evolutionary pressure that led to the expansion of the primate brain. Consistent with this notion, that functioning in the social world is crucial to our survival, while close supportive relationships are known to enhance well-being, a range of social stressors such as abuse, discrimination and dysfunctional relationships can increase the risk of psychiatric disorders. The centrality of the social world to our everyday lives is further exemplified by the fact that abnormality in social behaviour is a salient feature of a range of neurodevelopmental and psychiatric disorders. This paper aims to provide a selective overview of current knowledge of the neurobiological basis of our ability to form and maintain close personal relationships, and of the benefits these relationships confer on our health. Focusing on neurochemical and neuroendocrine interactions within affective and motivational neural circuits, it highlights the specific importance of cutaneous somatosensation in affiliative behaviours and psychological well-being and reviews evidence, in support of the hypothesis, that a class of cutaneous unmyelinated, low threshold mechanosensitive nerves, named c-tactile afferents, have a direct and specific role in processing affiliative tactile stimuli. PMID- 24210944 TI - Ecology of the ciguatera causing dinoflagellates from the Northern Great Barrier Reef: changes in community distribution and coastal eutrophication. AB - Ciguatera fish poisoning (CFP) is known to be caused by the ciguatoxins from the dinoflagellate genus Gambierdiscus, however, there is the potential for other toxins such as okadaic acid and dinophysistoxins from the genus Prorocentrum, and palytoxin from the genus Ostreopsis, to contaminate seafood. These genera may also be indicators of ecosystem health and potentially impact on coral reef ecosystems and the role they may play in the succession of coral to macroalgae dominated reefs has not been researched. Sixteen GBR field sites spanning inshore, mid-lagoon and outer lagoon (offshore) regions were studied. Samples were collected from September 2006 to December 2007 and abundance of benthic dinoflagellates on different host macroalgae and concentration of nutrients present in the water column were determined. The maximum abundance of Prorocentrum, Ostreopsis and Gambierdiscus found was 112, 793 and 50 cells per gram wet weight of host macroalgae, respectively. The average level of Dissolved Inorganic Nitrogen (DIN) in the water column across all sites (0.03 mg/L) was found to be more than double the threshold critical value (0.013 mg/L) for healthy coral reefs. Compared to a previous study 1984, there is evidence of a major shift in the distribution and abundance of these dinoflagellates. Inshore reefs have either of Prorocentrum (as at Green Island) or Ostreopsis (as at Magnetic Island) dominating the macroalgal surface niche which was once dominated by Gambierdiscus, whilst at offshore regions Gambierdiscus is still dominant. This succession may be linked to the ongoing eutrophication of the GBR lagoon and have consequences for the sources of toxins for ongoing cases of ciguatera. PMID- 24210943 TI - The role of maternal care in shaping CNS function. AB - Maternal care involves the consistent and coordinated expression of a variety of behaviours over an extended period of time, and adverse changes in maternal care can have profound impacts on the CNS and behaviour of offspring. This complex behavioural pattern depends on a number of integrated neuroendocrine mechanisms. This review will discuss the use of animal models in the study of the role of maternal care in shaping CNS function, the contributions of corticosteroid releasing hormone, vasopressin, oxytocin, and prolactin in this process, the molecular mechanisms involved, and the translational relevance of this research. PMID- 24210945 TI - Sublethal effects of a chlorinated and heated effluent on the physiology of the mussel, Mytilus edulis L.: a reduction in fitness for survival? AB - Coastal power stations entrain large volumes of cooling water, requiring biocidal treatment to prevent biological fouling. Discharged effluent is both heated and contaminated with residual traces of biocide and so it is necessary to quantify the impacts of this discharge. Cooling water from Heysham 2 nuclear power station, NW England, UK, is discharged to the intertidal area, via a culvert (to minimise erosion and maximise dilution and dispersion by directing the effluent into the receiving water at all states of the tide) within which the effluent is contained at low water. The culvert and surrounding coastal area support a population of blue mussels (Mytilus edulis). Mussel health was determined along a gradient of exposure, using three physiological indices: Scope for Growth, Gonad Mantle Index and Somatic Condition Index (K Factor). The Mussels within the culvert exhibited reduced physiological index values compared to an external site. A trend was identified down the length of the culvert, representing a gradient of exposure and indicating a potential negative effect on growth and reproductive output. PMID- 24210946 TI - Biodegradation of low-density polyethylene by marine bacteria from pelagic waters, Arabian Sea, India. AB - Sixty marine bacteria isolated from pelagic waters were screened for their ability to degrade low-density polyethylene; among them, three were positive and able to grow in a medium containing polythene as the sole carbon source. The positive isolates were identified as Kocuria palustris M16, Bacillus pumilus M27 and Bacillus subtilis H1584 based on the 16S rRNA gene sequence homology. The weight loss of polyethylene was 1%, 1.5% and 1.75% after 30 days of incubation with the M16, M27 and H1584 isolates, respectively. The maximum (32%) cell surface hydrophobicity was observed in M16, followed by the H1584 and M27 isolates. The viability of the isolates growing on the polyethylene surface was confirmed using a triphenyltetrazolium chloride reduction test. The viability was also correlated with a concomitant increase in the protein density of the biomass. Polyethylene biodegradation was further confirmed by an increase in the Keto Carbonyl Bond Index, the Ester Carbonyl Bond Index and the Vinyl Bond Index, which were calculated from FT-IR spectra. PMID- 24210947 TI - Quantitative analysis of plastic debris on recreational beaches in Mumbai, India. AB - Plastic litter was quantified on four sandy beaches in Mumbai. The mean abundance of 7.49 g and 68.83 items per square metre was recorded. The abundance of plastics significantly varied among the beaches showing an increasing trend in the southern part. The abundance of plastics by weight in Dadar was significantly higher than that in Aksa. The size fractionation of plastics proved that small particles (1-20 mm) are predominant with 41.85% microplastics (1-5 mm) which emphasizes the high risk to marine organisms due to possible ingestion. The highest quantity of microplastics was seen in Juhu beach (55.33%) followed by Versova, Aksa and Dadar. The major contributing factors for the abundance are beach usage for different activities such as recreational, religious and fishing which suggest that the land-based sources provide major inputs to plastic pollution in these beaches. PMID- 24210949 TI - The impact of timing of cholecystectomy following gallstone pancreatitis. AB - INTRODUCTION: Current guidelines for the management of acute gallstone pancreatitis recommend cholecystectomy as definitive treatment during primary admission or within 2 weeks of discharge, with the aim of preventing recurrent pancreatitis. However, cholecystectomy during the inflammatory phase may increase surgical complication rates. This study aimed to determine whether adherence to the guidelines prevents recurrent pancreatitis while minimising surgical complications. METHODS: Multi-centre review of seven UK hospitals, indentifying patients presenting with their first episode of gallstone pancreatitis between 2006 and 2008. RESULTS: A total of 523 patients with gallstone pancreatitis were identified, of which 363 (69%) underwent cholecystectomy (72 during the primary admission or within 2 weeks of discharge; 291 following this). Overall, 7% of patients had a complication related to cholecystectomy of which a greater proportion occurred when cholecystectomy was performed within guideline parameters (13% vs 6%; p = 0.07). 11% of patients were readmitted with recurrent pancreatitis prior to surgery, with those undergoing cholecystectomy outside guideline parameters being most at risk (p = 0.006). CONCLUSION: This study suggests cholecystectomy within guideline parameters significantly reduces recurrence of pancreatitis but may increase the risk of surgical complications. A prospective randomised study to assess the associated morbidity is required to inform future guidelines. PMID- 24210948 TI - Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication. AB - We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness. PMID- 24210951 TI - The regulation of proteolysis around the world. PMID- 24210950 TI - Environmental concentrations of the selective serotonin reuptake inhibitor fluoxetine impact specific behaviors involved in reproduction, feeding and predator avoidance in the fish Pimephales promelas (fathead minnow). AB - Pharmaceuticals and personal care products (PPCPs) have been found in surface waters worldwide, but little is understood of their effects on the wildlife that inhabit these waters. Fluoxetine (Prozac; Eli Lilly), a highly prescribed selective serotonin reuptake inhibitor (SSRI), is a commonly found PPCP in surface water. The purpose of this project was to determine if environmentally relevant concentrations of fluoxetine impact behavior that is important for population survival in native fish species, including reproduction, feeding and predator avoidance. Chronic 4-week exposures were conducted with doses ranging from 100 ng/L to 100 MUg/L to cover a range of environmentally relevant concentrations up to higher concentrations comparable to other published studies with the same drug that have documented various physiological impacts. Pimephales promelas (fathead minnow), a species native to North America, was used as it conducts a range of specific mating behaviors and therefore serves as an excellent model of specific impacts on brain function. Fluoxetine concentrations as low as 1 MUg/L, a concentration that has been found in many freshwater environments, were found to significantly impact mating behavior, specifically nest building and defending in male fish. Males were also found to display aggression, isolation, and repetitive behaviors at higher concentrations. Female mating behavior was largely unaffected. In addition, predator avoidance behaviors in males and females were also impacted at 1 MUg/L. Feeding was impacted at 10 MUg/L and in the highest exposure (100 MUg/L), egg production was limited by deaths of females due to significant male aggressive behaviors in the first two weeks of exposure. Specific behavioral changes occurred at each concentration (most noticeably 1 MUg/L and 100 MUg/L) indicating a dose dependent effect that triggered different responses at lower exposures versus higher exposures or differential impacts of dose depending on brain region. Length of exposure also had an impact on aggressive behavior. Changes in hormone levels, indicating significant neuroendocrine changes, suggested as a mechanism of response in higher dose and acute studies, were not linked to changes in behaviors at the doses used in this study. This research provides detailed data on how exposures to fluoxetine impact specific fish behaviors and reproduction and that the effects are dose dependent. PMID- 24210952 TI - A closer look at the relationship between the subdomains of social functioning, social cognition and symptomatology in clinically stable patients with schizophrenia. AB - Impairments in social functioning commonly seen in schizophrenia are thought to be mediated by deficits in the domains of social cognition. Some previous research has explored how social cognitive skills and psychotic symptoms are associated with social functioning, however these associations are still under debate. The main aim of this study was to investigate the relationship between different domains of social cognition and psychotic symptomatology, and also to look at the relationships with individual subdomains of social functioning within a clinically stable schizophrenia population. 45 outpatients were recruited and symptoms were assessed with the PANSS, and measures of emotion processing, affective and cognitive theory of mind (ToM), mental state reasoning attributional biases, and social functioning were taken. A correlational analysis was performed with the data. Following this, a regression analysis was used to reveal which domains of social cognition best predicted psychotic symptoms. In this stable group of patients, our results support the suggestion of a likely distinction between affective and cognitive components of ToM. The study also demonstrated that ToM and mental state reasoning were the best predictors of psychotic symptoms. Here we reveal that cognitive ToM had the most widespread relationship with social functioning, across multiple subdomains, while only some specific subdomains of social functioning correlated with other domains of social cognition and symptomatology. Further to this, positive symptoms were associated with much fewer subdomains of social functioning than negative and general symptoms. These findings imply that different aspects of social functioning may be served by different domains of social cognition and symptomatology. PMID- 24210953 TI - The effect of a rapid rehydration guideline on Emergency Department management of gastroenteritis in children. AB - This study evaluated the use and effect of a rapid rehydration guideline for the management of gastroenteritis in children 6months to 4years of age in an Emergency Department (ED). The guideline aims to facilitate rehydration within 4h of arrival to the ED, using oral or nasogastric fluids. Primary outcome measures were ED Length of Stay (LOS) and hospital admission rates. Documentation of physiological recovery and consistency of re-hydration regimes used were examined as secondary outcomes. METHODS: A quasi-experimental design using the medical records of 235 children pre and post intervention was used. Descriptive statistics (frequencies, medians, interquartile ranges) were used to summarize the data. The pre and post-test groups were compared using Chi Square and the Mann Whitney U Test. RESULTS: There was an increase in the ED LOS and in hospital admission rates post implementation of the rapid rehydration guideline in the ED. However, the time frame for initiation of rehydration therapy using oral or nasogastric routes improved post guideline implementation. CONCLUSION: The need for improvements in the ED management of dehydration secondary to gastroenteritis has been highlighted providing potential benefits to patient care and outcomes. PMID- 24210954 TI - The desired competence of the Swedish ambulance nurse according to the professionals - a Delphi study. AB - Nursing is evolving into new fields of health care including ambulance care, where a branch of specialist nursing is growing. Various views exist on the desired competence for the ambulance nurse and valid guidelines are lacking in Sweden. To increase knowledge of the field, professionals were asked to describe what competences an ambulance nurse should possess. The aim of this study was therefore to elucidate the desired professional competence of the specialist ambulance nurse, according to the professionals. A modified Delphi technique was used, where a panel of professional experts expressed their views on the desired competence of the ambulance nurse. This study reports, at a high level of agreement among the panel experts, that the desired competence of the specialist ambulance nurse consist of forty-four separate competences creating ten areas of competences: execute leadership, generic abilities, interpersonal communication, institutional collaboration, pedagogic skills, possession of relevant knowledge, professional judgement, professional skills, research activities, and technical skills. The high level of agreement among the professionals as well as the large number of competences reflects the high demands placed on the ambulance nurse by the professionals themselves. PMID- 24210955 TI - Impacts of the introduction of a triage system in Japan: a time series study. AB - The aim of the present study was to measure and compare the effectiveness of nursing triage before and after introduction of the Japanese Triage and Acuity Scale (JTAS), the Japanese version of the Canadian Triage and Acuity Scale (CTAS), during emergency treatment. Surveys of triage nurses and emergency physicians were conducted before and after JTAS introduction. Respondents were triage nurses (before 112 cases, after 94 cases), emergency physicians (before 50, after 41), and triaged patients (before 1057, after 1025) from seven separate emergency medical facilities. The results showed that nursing triage using the JTAS shortened "time from registration to triage" by 3.8min, "triage duration" by 1min, "time from registration to physician" by 11.2min, and "waiting time perceived by patients to see a physician" by 18.6min (p<0.001). The difference in assigned level of urgency between triage nurses and emergency physicians decreased from 34.2% to 12.2% (p<0.001), over-triage decreased from 24.7% to 8.6% (p<0.001), and under-triage decreased from 9.5% to 3.6% (p<0.001). Furthermore, assessment agreement between triage nurses and emergency physicians increased significantly, from weighted kappa=0.486 to weighted kappa=0.820. These findings suggest that the introduction of the JTAS promoted more effective nursing triage and medical care. PMID- 24210956 TI - Perpetuating proficiency in donor right hepatectomy for living donor liver transplantation. AB - BACKGROUND/OBJECTIVE: Donor right hepatectomy (DRH) was developed by master liver surgeons and has been applied in many liver transplant centers as the mainstay for adult living donor liver transplantation. It is a major and complex surgical operation performed on living liver donors for the benefit of liver recipients. The donors deserve the lowest though inevitable morbidity and mortality. In this study, the surgical outcomes of DRH performed by newer surgeons at an established center were studied to assess the transferability of the techniques of this standardized procedure. METHODS: We studied 450 consecutive DRHs performed by 11 surgeons. Three surgeons initiated and developed the transplant program and performed the first 200 DRHs (Era I). The role of chief surgeon in the following 250 DRHs (Era II) was gradually taken up by four newer surgeons with close guidance initially. RESULTS: Blood loss and operation time at the end of Era I versus the beginning of Era II were 251 vs. 341 mL and 391 vs. 497 minutes. The learning curve effect in Era I did not occur in Era II. The complication rates of the last 50 cases in Era I and Era II were 16% and 24%, respectively. Era I had one donor death whereas Era II had no donor death. CONCLUSION: At an established center, DRH can be carried out safely by newer surgeons with good outcomes. PMID- 24210957 TI - CD8 TCR beta chain repertoire expansions and deletions are related with immunologic markers in HIV-1-infected patients during treatment interruption. AB - BACKGROUND: HIV-1-infected individuals progressively loss CD4(+) T cells leading to immunosuppression and raising the risk of opportunistic infections. CD8(+) T cells play an important role in the immune response against virus infections through their TCR. OBJECTIVE: To evaluate the CD8-TCR repertoire and immunologic markers in HIV-1-infected patients. STUDY DESIGN: Ten chronic HIV-1-infected individuals on prolonged effective antiretroviral treatment (ART) were analyzed at baseline (before treatment interruption), after at least one year of treatment interruption (TI) and after at least one year from ART resume (TR). Twenty-four TCR-Vbeta gene families were analyzed by a modified CDR3 spectratyping method in isolated CD8(+) T-cells. Immune activation, exhaustion and subpopulation markers were analyzed by flow cytometry. RESULTS: Expansion of Vbeta10, Vbeta14 and Vbeta15 families, associated with low cell activation and stable exhaustion markers, were found at TI. Moreover, an increment of effector memory cells was found. Besides, depletion of Vbeta20, Vbeta28, and Vbeta29 families, associated with an increase in cell activation and exhaustion markers, at TI were also found. These alterations seemed to be more pronounced in patients who had longer time from diagnosis. ART seemed to restore altered CD8(+) T-cell repertoire and most of the immunologic markers. CONCLUSIONS: During TI (that was more pronounced in patients with longer HIV-1 infection) it was observed the expansion of Vbeta families correlated with decreased cell activation, while Vbeta families correlated with cell activation and exhaustion were depleted. These specific repertoire alterations reverted after ART resume. PMID- 24210959 TI - Comment on: Fulminant myocarditis and viral infection. PMID- 24210958 TI - Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients. AB - BACKGROUND: Hepatitis E virus (HEV) genotype 3 is recognised as an emerging pathogen in industrialised countries. The currently commercially available HEV specific enzyme linked immunosorbent assays (ELISAs) are primarily designed for the detection of antibodies against genotypes 1 (Burma) and 2 (Mexico) and may not sensitively detect HEV genotypes 3 or 4. OBJECTIVES: This study aimed to evaluate the analytical and clinical performances of eight commercially available HEV serum antibody immunoglobulin M (IgM)- and immunoglobulin G (IgG)-specific ELISAs for genotype 1 and 3 HEV infections in a clinical setting and to study the antibody responses against HEV of immunocompromised versus immunocompetent patient groups. STUDY DESIGN: Analytical performance and diagnostic sensitivity and specificity were assessed using well-defined reference samples and samples from patients with polymerase chain reaction (PCR)-confirmed HEV infection (n=88) and a specificity panel (n=98). RESULTS: Limiting dilutions indicated that the highest analytical sensitivity in head-to-head comparison was measured for the Mikrogen_new IgG assay. Taking the serum working dilutions of each assay into account, the Wantai IgG assay was the most sensitive assay. Receiver operator curve (ROC) analysis showed area under the curve (AUC) values of 0.943, 0.964, 0.969, 0.971, 0.974 and 0.994 for the DSI, Mikrogen_old, MP Diagnostics, Mikrogen_new, Wantai and DiaPro anti-HEV IgM assays, respectively. The highest specificity of currently available assays was found for the IgM Wantai assay (>99%). If anti-HEV IgM and IgG results from each supplier were combined, DSI and Wantai assays were able to detect the highest number of (passed) HEV infections. CONCLUSIONS: Our study showed that current commercial HEV ELISAs could be used to diagnose HEV genotype 3 infection adequately in a clinical setting. PMID- 24210961 TI - Regional brain activity change predicts responsiveness to treatment for stuttering in adults. AB - Developmental stuttering is known to be associated with aberrant brain activity, but there is no evidence that this knowledge has benefited stuttering treatment. This study investigated whether brain activity could predict progress during stuttering treatment for 21 dextral adults who stutter (AWS). They received one of two treatment programs that included periodic H2(15)O PET scanning (during oral reading, monologue, and eyes-closed rest conditions). All participants successfully completed an initial treatment phase and then entered a phase designed to transfer treatment gains; 9/21 failed to complete this latter phase. The 12 pass and 9 fail participants were similar on speech and neural system variables before treatment, and similar in speech performance after the initial phase of their treatment. At the end of the initial treatment phase, however, decreased activation within a single region, L. putamen, in all 3 scanning conditions was highly predictive of successful treatment progress. PMID- 24210960 TI - Aberrant functional connectivity between motor and language networks in rolandic epilepsy. AB - INTRODUCTION: Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. MATERIALS AND METHODS: Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. RESULTS: Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p<0.01). For this connection, lower connectivity was associated with lower language scores in the patient group (r=0.49, p=0.02), but not in the controls. CONCLUSION: Language laterality analysis revealed bilateral language representation in the age range under study (8-14 years). As a consequence, the connection of reduced functional connectivity we found represents an impaired interplay between motor and language networks, and aberrant functional connectivity associated with poorer language performance. These findings provide a first neuronal correlate in terms of aberrant resting state functional connectivity for language impairment in RE. PMID- 24210963 TI - The evolution of distributed association networks in the human brain. AB - The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling. PMID- 24210962 TI - Cognitive aging: is there a dark side to environmental support? AB - It has been known for some time that memory deficits among older adults increase when self-initiated processing is required and decrease when the environment provides task-appropriate cues. We propose that this observation is not confined to memory but can be subsumed under a more general developmental trend. In perception, learning or memory, and action management, older adults often rely more on external information than younger adults do, probably both as a direct reflection and indirect adaptation to difficulties in internally triggering and maintaining cognitive representations. This age-graded shift from internal towards environmental control is often associated with compromised performance. Cognitive aging research and the design of aging-friendly environments can benefit from paying closer attention to the developmental dynamics and implications of this shift. PMID- 24210964 TI - Light microscopy mapping of connections in the intact brain. AB - Mapping of neural connectivity across the mammalian brain is a daunting and exciting prospect. Current approaches can be divided into three classes: macroscale, focusing on coarse inter-regional connectivity; mesoscale, involving a finer focus on neurons and projections; and microscale, reconstructing full details of all synaptic contacts. It remains to be determined how to bridge the datasets or insights from the different levels of study. Here we review recent light-microscopy-based approaches that may help in integration across scales. PMID- 24210965 TI - Mediastinal abscess and esophageal stricture following voice prosthesis insertion. AB - The use of a tracheo-esophageal voice prosthesis is a well-established procedure to restore the voice in total laryngectomees. The insertion of the prosthesis is not a risk-free procedure, various complications having been reported especially in irradiated patients. Here described is a case of an esophageal rupture after secondary tracheo-esophageal puncture with mediastinal abscess in a patient previously treated with pharyngo-laryngectomy and subsequent radiotherapy for a left pyriform sinus carcinoma, which required immediate surgical drainage through a left cervical approach. Few weeks after surgical drainage an esophageal stricture at the site of the rupture developed, which was only temporarily resolved after the insertion of biodegradable esophageal stents, followed by re stenosis once the reabsorption of the stent took place. PMID- 24210966 TI - In vitro development of goat-sheep and goat-goat zona-free cloned embryos in different culture media. AB - The gradual decline in the genetic diversity of farm animals has threatened their survival and risk of their extinction has increased many fold in the recent past. Endangered species could be rescued using interspecies embryo production. The objective of this study was to investigate the effect of three different culture media on the development of Handmade cloned intraspecies (goat-goat) and interspecies (goat-sheep) embryo reconstructs. Research vitro cleave media (RVCL) yielded higher cleavage and morula-blastocyst development in intraspecies and interspecies nuclear transfer groups compared with G1.G2 and modified synthetic oviductal fluid (mSOFaaci). Cleavage frequency of intraspecies cloned embryos in RVCL, mSOFaaci, and G1.G2 did not differ significantly (87.12%, 82.45%, and 92.52%, respectively). However, the morula/blastocyst frequency in RVCL was greater in mSOFaaci and G1.G2 (51.18% vs. 38.28% vs. 36.50%, respectively). Cleavage and morula/blastocyst frequency in interspecies cloned embryos was greater in RVCL than in mSOFaaci and G1.G2 (76.14% and 42.3% vs. 65.9% and 38.3% vs. 58.56% and 33.1%, respectively). Goat oocytes were parthenogenetically activated and cultured in RVCL, mSOFaaci, and G1.G2 and kept as control. Cleavage and morula/blastocyst frequency in this group was greater in RVCL than in mSOFaaci and G1.G2 (89.66% and 65.26% vs. 85.44% and 48.05% vs. 86.58% and 42.06%, respectively). Conclusively, the results suggest that not only can the interspecies embryos of goat be produced using sheep oocytes as donor cytoplast but also the percentages can be improved by using RVCL media for culturing of the embryos. PMID- 24210968 TI - [A surgical follow-up platform to reduce complications in free flap surgery]. AB - STUDY OBJECTIVE: In 2007, the WHO adopted surgical safety as the theme for the 2nd global patient safety challenge. Measurement of surgical services was identified as a surgical care area in need of major improvements. Aware of this recommendation, a preliminary study was conducted in our hospital and showed that the incidence of complete necrosis in free flap surgery was 10.0 %, a rate among the highest found in medical literature. In that context, an interactive surgical follow-up platform (PICS) was implemented to monitor outcomes in free flap surgery. The hypothesis was to reduce the short-term failure of microsurgical reconstructions. PATIENTS AND METHODS: In Summer 2010, the tool for capturing and analyzing data (PICS) was implemented. All patients who underwent free flap reconstruction were prospectively registered in the platform. The primary endpoints to evaluate the effectiveness of the tool are the rates of surgical re exploration and complete necrosis of the flap. RESULTS: From May 2010 to December 2011, 129 cases of free flap reconstruction were recorded. The rate of total flap necrosis was 10.0 % before database introduction and declined to 3.1 % afterwards (P<0.05). Take-backs occurred in 27.0 % of free flap reconstructions at baseline and in 10.1 % after implementation (P<0.01). CONCLUSION: The implementation of PICS is associated with a significant improvement of postoperative short-term outcomes in free flap surgery. This tool is effective to evaluate care services and provides an increased surgical safety for patients. Surgical teams are encouraged to implement a data collection tool in order evaluate operative care on a routine basis. PMID- 24210969 TI - Intractable vomiting: a case of severe gastroparesis after Ramsay Hunt syndrome. PMID- 24210970 TI - Cutaneous human papillomavirus types detected on the surface of male external genital lesions: a case series within the HPV Infection in Men Study. AB - BACKGROUND: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [beta]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES: To examine cutaneous beta-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. STUDY DESIGN: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. RESULTS: beta-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of beta-HPV types detected on condylomas. Most beta-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. CONCLUSIONS: EGLs and the normal genital skin of men harbor a large number of beta-HPV types; however, it appears that beta-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals. PMID- 24210971 TI - A novel core biopsy technique for anterior cruciate ligament preserves ligament structural integrity: a porcine study. AB - PURPOSE: The objective of this study was to validate a new technique to safely obtain core biopsy specimens of the anterior cruciate ligament (ACL) without jeopardizing the ACL's biomechanical properties. METHODS: Eleven pairs of fresh porcine femur-ACL-tibia complexes were tested in a loading frame. The ACL of one knee was biopsied using a spring-loaded core biopsy device, whereas the contralateral ACL was tested as the control. Biomechanical properties of the biopsied and control ACLs were compared. RESULTS: The ultimate load to failure was 1,202 N +/- 171.1 N and 1,193 N +/- 228.7 N (P = .8984) for biopsied and non biopsied ACLs, respectively. No significant differences were noted for maximal elongation at failure, maximal strain, absorbed energy, and stiffness between biopsied and non-biopsied ACLs. CONCLUSIONS: The results of this study indicate that a new ACL core biopsy technique can be performed while preserving the ligament's structural integrity. CLINICAL RELEVANCE: The presented core biopsy technique could be regarded as a dedicated tool to elucidate the poorly understood (patho)biological processes occurring in both the native and reconstructed ACLs. PMID- 24210972 TI - Hydropneumomediastinum secondary to gastric volvulus perforation in a patient with giant hiatal hernia. PMID- 24210973 TI - A content analysis of food references in television programming specifically targeting viewing audiences aged 11 to 14 years. AB - OBJECTIVE: Examine food in cable television programming specifically targeting 11 to 14-year-olds ("tweens"). DESIGN: Content analysis of food-related scenes (FRS)-in which food was shown, mentioned, and/or consumed-in 880 minutes of programming was conducted. SETTING: Five days of afternoon/early evening television programs on the Disney Channel. MAIN OUTCOME MEASURES AND ANALYSIS: Food references were compared with USDA MyPlate and classified according to modified Ratio of Recommended to Restricted Food Components. RESULTS: The authors found 331 FRS, averaging 16.6 scenes/h. Preponderance of FRS was physiological needs (40.7%), followed by display (10%), party (8.5%), social event (8%), and retail store (6.6%). Snacks dominated 41% of FRS, and breakfast, lunch, and dinner were much lower in frequency. Half of FRS was visual only, followed by verbal only. Food references were not congruent with MyPlate recommendations; 42% of food items did not fit into MyPlate food groups. Only 24% of food items were fruit or vegetables, which is considerably less than recommended by MyPlate guidelines. Using modified Ratio of Recommended to Restricted Food Components, 66% of food items scored < 1.0, signifying less nutritious. CONCLUSIONS AND IMPLICATIONS: Tween television programming regularly includes non-nutritious food, which likely influences tweens' attitudes and behaviors. Television programming may consider past approaches to tobacco smoking and health messages on television. More attention is warranted regarding television programming by nutrition educators, researchers, health professionals, and industry specialists. PMID- 24210974 TI - Assessment of cytotoxic and immunomodulatory properties of four antidepressants on primary cultures of abalone hemocytes (Haliotis tuberculata). AB - Pharmaceutical compounds like antidepressants found in surface waters raise concerns due to their potential toxicity on non-target aquatic organisms. This study aimed at investigating the in vitro cytotoxicity and immunomodulatory properties of four common antidepressants, namely Amitriptyline, Clomipramine, Citalopram and Paroxetine, on primary cultures of abalone hemocytes (Haliotis tuberculata), after 48 h-exposure. Effects on immunocompetence (phagocytosis, levels of reactive oxygen species, esterase activity and lysosomal membrane destabilization) were assessed. Results obtained by MTT assays revealed that acute toxicity is unlikely to occur in the environment since the LC50s of the four antidepressants are at the mg/L level. The different immunological endpoints displayed a biphasic response, with an increase at the lowest concentration (i.e. 1 MUg/L) followed by a decrease at higher concentrations. Overall, Amitriptyline and Clomipramine, the two tricyclic antidepressants, had higher immunomodulatory capacities than the two selective serotonin reuptake inhibitors Citalopram and Paroxetine. Amitriptyline was the most potent and Citalopram the least potent drug in altering immune function in H. tuberculata. PMID- 24210975 TI - [Impact factor and h index of Spanish biomedical journals]. PMID- 24210976 TI - [Linear lichen planus]. PMID- 24210977 TI - [A 24-year old man with fever and pulmonary infiltrates]. PMID- 24210978 TI - [Diagnostic ability of Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease-4 equations to estimate glomerular filtration rate in with multimorbidity patients]. AB - BACKGROUND AND OBJECTIVE: The Modification of Diet in Renal Disease (MDRD) equation is recommended by most scientific societies to calculate the estimated glomerular filtration rate (GFR). Recently the group Chronic Kidney Disease Epidemiology Collaboration (CKP-EPI) has published a new, more precise and accurate equation. We have analyzed its behavior in a group of polypathological patients (PP) and compared it with the classic MDRD-4.version PATIENTS AND METHOD: Multicenter, observational, descriptive and transversal study. We calculated GFR by MDRD-4 and CKD-EPI in 425 PP. Each stage was assigned according to the GFR: 1:>90; 2: 60-89; 3: 30-59; 4: 15-29; and 5 < 15 ml/min/1.73m(2). We analyzed the correlation between both and the patients reclassified by CKD-EPI. RESULTS: Mean age was (mean [SD]) 81.7 (7.9) years. 55.3% were women. The mean estimated GFR was 58.6 (26.3) ml/min/1,73m(2) by MDRD-4 and 52.7 (23.0) ml/min/1.73m(2) by CKD-EPI (P<.001; Spearman's Rho correlation and Lin concordance coefficients: 0.993 and 0.948). The Bland-Altman plots reflected lower values for GFR for CKD-EPI equation. In the stage 2, 21.2% were reclassified by CKD-EPI to the stage 3, with women older than 83 years being the more disadvantaged subgroup with 27.3% or reclassification. CONCLUSION: CKD-EPI equation applied to PP worsens the results of MDRD-4. In general, it originates low values of GFR and increases the degree of renal insufficiency, especially in older women. PMID- 24210980 TI - [Screening of intraepithelial anal neoplasm]. PMID- 24210979 TI - [Dermoscopy in cutaneous parasitosis]. PMID- 24210981 TI - [Opportunities for improvement in the management of osteoporosis. Time to tackle the essential]. PMID- 24210982 TI - [Usefulness of the Chronic Obstructive Pulmonary Disease Assessment Test in chronic obstructive pulmonary disease with severe airflow limitation]. AB - BACKGROUND AND OBJECTIVE: To evaluate the relationship between Chronic Obstructive Pulmonary Disease Assessment Test (CAT questionnaire) and chronic obstructive pulmonary disease (COPD) severity assessed by the multidimensional BODE index in patients with severe airflow obstruction (forced expiratory volume in one second [FEV1] post-bronchodilator<50%) in a stable state. MATERIAL AND METHOD: Prospective observational study (2012). We classified the severity of COPD according to the BODE index in 3 subgroups: mild to moderate COPD (BODE<5 points), severe COPD (BODE 5-6 points) and very severe COPD (BODE >= 7 points). RESULTS: We included 97 patients with a mean age of 67 (8) years, 96% were men. The mean FEV1 was 34.3% (9.8%) and mean BODE index was 4.8 (1.4). The mean CAT score was 20 (7.7). We found no significant differences in CAT score (total or by items) between the 3 groups of BODE assessed. CONCLUSIONS: In patients with COPD and severe airflow obstruction, the CAT score reflects a moderate to severe impact of illness and does not allow to predict COPD severity assessed by the BODE index. PMID- 24210983 TI - [Results of an early intervention program for patients with bacteremia discharged from the Emergency Department]. AB - BACKGROUND AND OBJECTIVE: Occult bacteremia represents 3% of blood cultures drawn in the Emergency Department. In most cases, the evolution is unknown. The aim of the study is to analyze the results obtained after implementation of an intervention program for these patients. PATIENTS AND METHODS: We describe the results of an early intervention program for patients with bacteremia in the Emergency Department discharged at home, which was implemented in daily clinical activity in Costa del Sol Hospital in Marbella (Malaga). We analyze the epidemiological, microbiological, Charlson comorbidity index, Pitt bacteremia index and 30-day mortality. RESULTS: During 15 months, 90 patients were located. The median age was 67 years. There was a predominance of males with 54 of cases (60%). The acquisition place was predominantly the community with 51 cases (56.6%), being the most frequent microorganism Escherichia coli with 31 cases (34.4%). The median Charlson index and the bacteremia Pitt index were 1. Thirty eight of the cases required hospitalization (42.2%). Pitt bacteremia index>1 and exchange antibiotic treatment were the related variables with need for admission. One patient died (1.2%) and 6 patients could not be located (6.6%). CONCLUSIONS: The implementation of programs of early identification and management of patients with bacteremia in Emergency Department discharged al home allows early recovery of patients who require hospital admission and antibiotic treatment optimization. In our series, mortality after early intervention was low (1.2%). PMID- 24210984 TI - [Acquired reactive perforating collagenosis as a paraneoplastic syndrome of lung adenocarcinoma]. PMID- 24210985 TI - [Aquagenic palmoplantar keratoderma in children with cystic fibrosis]. AB - INTRODUCTION: Aquagenic palmoplantar keratoderma (APK) is a cutaneous phenomenon marked by the formation of edematous, translucent papules and plaques on the palms after water immersion. It can be observed in healthy subjects, but while this dermatosis is little known by practitioners treating these patients, most cases of APK have been described in patients with cystic fibrosis (CF). The primary objective of this study was to evaluate the frequency of APK in a population of children with CF. In addition, the relationship between APK and sex, genotype, pancreatic and pulmonary function, body mass index, and sweat chloride levels was analyzed. METHODS: This study was conducted in 60 children, 27 girls and 33 boys, aged 4 months to 18 years, followed at the CF care center at Angers (France) University Hospital, in whom CF had been confirmed by a positive sweat chloride level greater than 60 mmol. APK was determined by questioning searching for modifications of the palms noticed by the patient or his/her family after immersion in water and a clinical examination searching for the same signs before and after immersion of the right hand in a bucket of lukewarm water for 3 minutes (bucket sign). RESULTS: Forty-seven out of 60 children (78%) had a positive bucket sign. Thirty-eight upon these 47 children had already noticed modifications of the skin on their palms, appearing quickly during the bath and 6 had an edema and an increase in skin folds on the palms of the hands even before immersion of their hand in water. No genotype-phenotype correlations were detected in patients with APK, nor were there associations of APK with other phenotypic features of CF. CONCLUSION: APK is very frequent in patients with CF. It is most probably a consequence of the dysfunction of the CFTR protein. It should be systematically sought in all patients with CF. Its discovery in another context should suggest the diagnosis of CF or a carriage to the heterozygous state of a mutation involved in the disease. PMID- 24210986 TI - [Trisomy 21 in visual art]. AB - In 1866, J. Langdon Down published a paper on "an ethnic classification of idiots" and noted their facial resemblance with individuals of the Mongolian people. In 1959, J. Lejeune, M. Gautier, and R. Turpin demonstrated that the children with Down syndrome had an extra copy of chromosome 21. There is now a debate within the medical literature on the age of trisomy 21 as a disease affecting mankind. Since it was not described before 1866, some authors questioned whether this disease is an old or new condition in humans. Three methods of investigation are useful for demonstrating that trisomy 21 has been present in humans for a long time: the figuration of this condition in historical paintings, figurines, and pottery; its presence in old skeletal remains; and the origin of human chromosome 21 during primate phylogeny. Figurines strongly suggestive of trisomy 21 have been found in the Greco-Roman world, in many Central and South American pre-Columbian cultures, and in Khmer temples. In Europe, during the Renaissance, Italian and Flemish artists represented trisomy 21 in paintings of religious inspiration. Studies on the origin and pathology of chromosome 21 have shown that the ancestral human chromosome 21 arose 30-50 million years ago and that trisomy 21 has existed since time immemorial. PMID- 24210987 TI - Prevalence, predictors and evolution of echocardiographically defined cardiac abnormalities in adults with type 1 diabetes: an observational cohort study. AB - AIMS/HYPOTHESIS: The aims of this observational study were to determine the prevalence and predictors of an abnormal echocardiogram in adults with type 1 diabetes, and to assess the evolution of changes in a subset of subjects. METHODS: Cardiac function and structure were prospectively investigated by comprehensive transthoracic echocardiographic techniques in asymptomatic adults with type 1 diabetes seen in the ambulatory care setting. RESULTS: We recruited 136 subjects (mean age 39 years, SD 14 years) with a median diabetes duration of 21 years [25(th), 75(th) interquartile range; 11, 29]. An abnormal echocardiogram was present in 29% of subjects; diastolic dysfunction in 69%, left ventricular hypertrophy in 38% and systolic dysfunction in 10%. The independent predictors of an abnormal echocardiogram were age, with a 9-fold increase in those >=40 years (OR 9.40 [95% CI 2.68-33.04], P <0.0001), and increased body mass index (BMI), with a 17% increase in risk (P=0.04). A second echocardiogram was available in 65 subjects (3.8+/-1.7 years later). The results showed that one in five with a normal first study had developed an abnormal second study, mainly diastolic dysfunction, with age being the only independent predictor of progression (P=0.006). CONCLUSIONS/INTERPRETATION: Subclinical echocardiographic abnormalities are common in asymptomatic type 1 diabetes adults, and changes are progressive. The addition of an echocardiogram to complication surveillance programs in those with type 1 diabetes aged >=40 years may represent a cost effective way to screen for, and aggressively treat, occult cardiac disease. PMID- 24210990 TI - Giant anorectal mucosal melanoma. PMID- 24210991 TI - Endoscopic treatment of iatrogenic gastrointestinal perforations: an overview. AB - In the past, the treatment of iatrogenic gastrointestinal perforations was limited to surgical management or to medical observation. Natural Orifice Transluminal Endoscopic Surgery (NOTES) has paved the way towards the development of reliable endoscopic closure techniques, which can be applicable in accidental perforations of the gastrointestinal tract. When endoscopic treatment is feasible, hemoclips are preferred in smaller perforations, while over-the-scope clips or a combination of hemoclips, endoloops, and glue are used in larger ones. Endoscopic stitching is rarely utilized, and endoscopic stapling has been practically abandoned. The use of self-expandable covered stents can be considered in the esophagus and duodenum. Broad spectrum antibiotics are recommended in most cases. Clinical follow-up in a medico-surgical unit is mandatory and surgical intervention should not be delayed more than 24h if clinical or biological worsening occurs. Imaging with oral contrast medium is advisable before resumption of oral feeding in the case of large perforations. PMID- 24210992 TI - Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract. AB - BACKGROUND: Endomicroscopy allows in vivo microscopic investigation of enteral mucosa during endoscopic examinations. The aim of this study was to determine interobserver variability in the evaluation of endomicroscopic pictures of several organs by groups of investigators composed of confocal experts, pathologists and students. METHODS: Twenty-five selected representative endomicroscopic pictures of the colon, stomach and oesophagus (total number, 75) were evaluated based on tissue, inflammatory and neoplastic changes (secondary endpoints). The endomicroscopic presence of neoplastic features was the primary endpoint and correlated with the final histological diagnosis. RESULTS: The kappa values for experts examining colon, stomach, and oesophagus pictures were 0.80, 0.91, and 0.488, respectively; for students 0.74, 0.684, and 0.527 and for pathologists 0.749, 0.633, and 0.346, respectively. Neoplasia was accurately diagnosed in 67-97% of patients with no significant differences between the 3 groups. Tissue differentiation was determined best by pathologists, whereas the degree of inflammation was better diagnosed by experts and students. In all 3 groups the diagnosis of oesophageal diseases was the most difficult. CONCLUSIONS: Endomicroscopic images can be interpreted with high concordance. In our study, the diagnostic reliability was not different between students, endomicroscopic experts, and pathologists. Thus, endomicroscopy could be an additional and reliable imaging modality for diagnosing mucosal neoplasia of the gut. PMID- 24210993 TI - Phosphorylated Crkl reduction levels are associated with the lowest P glycoprotein activity levels in cells from chronic myeloid leukemia patients. AB - ABCB1/P-glycoprotein (Pgp) and ABCG2/BCRP overexpression have been described as related to imatinib resistance in chronic myeloid leukemia (CML). We showed in CML cells from 55 patients that Pgp activity was more frequently detected than BCRP activity (p=0.0074). Imatinib-induced Crkl phosphorylated protein (pCrkl) reduction was more pronounced in K562 (Pgp-negative) than in K562-Lucena (Pgp positive) CML cell line. Expressive pCrkl reduction levels after in vitro imatinib treatment was observed in samples from patients exhibiting lower Pgp activity levels compared with patients exhibiting higher Pgp activity levels (p=0.0045). Pgp activity in association with pCrkl reduction levels might help to distinguish between imatinib-resistant and imatinib-sensitive CML cells. PMID- 24210994 TI - Global complexity and cognitive reserve in MCI. PMID- 24210995 TI - How task specific is task specific dystonia? PMID- 24210996 TI - Psychophysiological correlates of coping and quality of life in patients with ALS. AB - OBJECTIVE: Self-regulation models of coping suggest that patients with chronic diseases reporting low quality of life (QoL), an indicator of failed coping efforts, should show facilitated access to disease related words. Here we investigated whether a reduced N400 amplitude within an incongruent, i.e. unpredictable disease-related context would be a correlate of this facilitated access. METHODS: ERPs were recorded in N=18 patients with amyotrophic lateral sclerosis (ALS) and N=20 age-matched healthy controls during reading of sentences, ending either with congruent or incongruent words. Incongruent and congruent words were disease related or disease unrelated. Mean N400 amplitudes were analyzed with mixed models. RESULTS: Generally, incongruent words elicited a more negative N400 amplitude than congruent words in all groups and conditions, i.e. an N400 effect. In patients with high QoL this N400 effect did not differ between disease related and unrelated words. In patients with low QoL, however, the N400 effect was significantly smaller for disease related than for disease unrelated words. In healthy controls N400 amplitudes showed no such interaction between congruence, disease relatedness and QoL. Results remained stable when controlling for disease severity, duration and depression. CONCLUSION: The N400 indicates increased accessibility to disease related information in ALS patients with low QoL. The increased access may imply a constantly activated disease related context which is linked to low QoL. SIGNIFICANCE: N400 modulation by disease related information may serve as a psychophysiological correlate of coping and the patient's QoL. PMID- 24210998 TI - We were blind, so now we can see: the EP/ERP story in migraine. PMID- 24210997 TI - Brain activity during complex imagined gait tasks in Parkinson disease. AB - OBJECTIVE: Motor imagery during functional magnetic resonance imaging (fMRI) allows assessment of brain activity during tasks, like walking, that cannot be completed in an MRI scanner. We used gait imagery to assess the neural pathophysiology of locomotion in Parkinson disease (PD). METHODS: Brain activity was measured in five locomotor regions (supplementary motor area (SMA), globus pallidus (GP), putamen, mesencephalic locomotor region, cerebellar locomotor region) during simple (forward) and complex (backward, turning) gait imagery. Brain activity was correlated to overground walking velocity. RESULTS: Across tasks, PD exhibited reduced activity in the globus pallidus compared to controls. People with PD, but not controls, exhibited more activity in the SMA during imagined turning compared to forward or backward walking. In PD, walking speed was correlated to brain activity in several regions. CONCLUSIONS: Altered SMA activity in PD during imagined turning may represent compensatory neural adaptations during complex gait. The lowered activity and positive correlation to locomotor function in GP suggests reduced activity in this region may relate to locomotor dysfunction. SIGNIFICANCE: This study elucidates changes in neural activity during gait in PD, underscoring the importance of testing simple and complex tasks. Results support a positive relationship between activity in locomotor regions and walking ability. PMID- 24210999 TI - New SSU-rDNA sequences for eleven colpodeans (Ciliophora, Colpodea) and description of Apocyrtolophosis nov. gen. AB - Using 11 new SSU-rDNA sequences, we analyze relationships within the class Colpodea, especially of some uncommon taxa, such as Kalometopia duplicata, Cyrtolophosis minor, and Jaroschia sumptuosa. The sequences do not change the basic structure of the molecular Colpodea tree, i.e., all belong to one of the four molecular clades recognized by Foissner et al. (2011): Colpodida, Cyrtolophosidida, Bursariomorphida, and Platyophryida. The addition of three Colpoda sequences strengthens the observation that species of this genus are distributed over the whole molecular Colpodea tree. Very likely, this is caused by a fast radiation of Colpoda, several species of which then evolved independently, forming new genera and families. Cyrtolophosis minor, which belongs to the molecular Pseudocyrtolophosis clade, is referred to a new genus, Apocyrtolophosis nov. gen., characterized by a comparably large, deltoid oral opening, an unciliated posterior region, and the absence of an oblique kinety in the left oral polykinetid. Bryometopus triquetrus does not erase the paraphyly of its genus. Platyophrya vorax, P. spumacola, and P. bromelicola form a highly supported clade in the order Platyophryida. Platyophryides and Ottowphrya are close genetically but differ in the silverline pattern (colpodid vs. platyophryid). PMID- 24211000 TI - Effect of patient-controlled sedation with propofol on patient satisfaction: a randomized study. AB - BACKGROUND: In this trial we sought to determine whether propofol-based patient controlled sedation (PCS) during diagnostic cerebral angiography would result in improved patient satisfaction compared to placebo-based PCS. METHODS: We randomly assigned 61 patients to receive propofol-based PCS (n=33, 15mg bolus in 9 s) or placebo-based PCS (n=28, bolus of 1.5mL of a 20% lipid emulsion in 9 s). We recorded the number of PCS bolus requirements, the need for rescue sedative drugs, and physiological variables. Prior to the procedure, the anxiety level of each patient was evaluated using the Anxiety State Traits Assessment (STAI) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The quality of patient conditioning was quoted by both the anesthetist and neuroradiologist using Visual Analog Scale (VAS). The day following the procedure, patients were given the EVAN questionnaire, a validated tool for assessing patient satisfaction. RESULTS: Both groups were similar in term of demographics, American Society of Anesthesiologist (ASA) physical status scores, STAI and APAIS scores, and procedure lengths. There were no differences between groups in EVAN scores 76.9+/-16.1 vs. 75.7+/-12.8; P=0.78. The number of PCS bolus requirements was significantly higher in the placebo group 3.96+/-9.5 vs. 3.13+/-3.1 (P=0.02). No adverse event was recorded. CONCLUSION: This prospective, double-blind, randomized study showed that sedation using propofol PCS did not improve patients' satisfaction during diagnostic cerebral angiography. Therefore, an anesthetist should be rapidly available on request but not necessarily present during the whole procedure. PMID- 24211001 TI - [Necrotizing pneumonia due to Enterococcus faecalis in an immunocompromised patient of 67 years]. PMID- 24211002 TI - [History of pediatric anesthesia: from the beginnings to the end of the 19th century]. AB - The first intuitions and descriptions of anesthesia can be found in the antique civilizations. In the 19th century, the invention of anesthesia took place in Boston, and quickly spread to Europe. In France, regulations and structures were created before the beginning of the 20th century to organize this new profession, for children as well as for adults. PMID- 24211006 TI - Anti-NMDAR autoimmune encephalitis. AB - The N-methyl-D-aspartate receptor (NMDAR) is involved in normal physiological and pathological states in the brain. Anti-NMDAR encephalitis is characterized by memory deficits, seizures, confusion, and psychological disturbances in males and females of all ages. This type of encephalitis is often associated with ovarian teratoma in young women, but children are less likely to have tumors. Anti-NMDAR encephalitis is a neuroimmune syndrome in patients with autoantibodies recognizing extracellular epitopes of NMDAR, and the autoantibodies attenuate NMDAR function through the internalization of NMDAR. Following the initial symptoms of inflammation, the patients show the various symptoms such as memory loss, confusion, emotional disturbances, psychosis, dyskinesis, decrease in speech intelligibility, and seizures. About half of these patients improved with immunotherapy including high-dose intravenous corticosteroids and intravenous immunoglobulins is administrated to these patients, but the patients who had no improvement with these therapy require further treatments with rituximab or cyclophosphamide. It is necessary to detect anti-NMDAR antibodies at early stages, because the prognosis of these patients may be improved by early treatment. Recovery is slow, and the patients may have some disturbances in their motor function and cognition. The pathologic mechanism underlying the development of anti-NMDAR encephalitis has been elucidated gradually, but the optimal treatment has not yet been clarified. Further studies are required to clarify in detail the mechanism underlying anti-NMDA encephalitis and to develop effective treatments. PMID- 24211003 TI - Dissociation of preparatory attention and response monitoring maturation during adolescence. AB - OBJECTIVE: Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound "bottom-up" to more mature executive-driven "top-down" processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN). METHODS: CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11-18 years, using a variation of a letter discrimination task. RESULTS: Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied. CONCLUSIONS: The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring. SIGNIFICANCE: This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes. PMID- 24211007 TI - Resting state functional connectivity alterations in primary lateral sclerosis. AB - Resting state functional connectivity of the sensorimotor and extramotor brain networks was studied in 24 patients with primary lateral sclerosis (PLS) relative to 26 healthy controls. The relationships of RS functional connectivity with patient clinical and cognitive status and white matter tract damage (i.e., corticospinal tracts, corpus callosum, and superior longitudinal fasciculus) were investigated. Compared with controls, PLS patients showed an increased functional connectivity within the sensorimotor, frontal, and left frontoparietal networks spanning the pre- and postcentral, medial and dorsal frontal, insular, and superior temporal regions. Patients with more severe physical disability and a more rapid rate of disease progression had increased sensorimotor connectivity values. The increased functional connectivity within the frontal network was associated with executive dysfunction. In addition, higher functional connectivity correlated with greater structural damage to network-specific white matter tracts. This study shows clinically meaningful increased resting state functional connectivity in PLS. PMID- 24211008 TI - Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials: effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size. AB - The objective of this study was to evaluate the effect of computational algorithm, measurement variability, and cut point on hippocampal volume (HCV) based patient selection for clinical trials in mild cognitive impairment (MCI). We used normal control and amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) as normative reference and screening cohorts. We evaluated the enrichment performance of 4 widely used hippocampal segmentation algorithms (FreeSurfer, Hippocampus Multi-Atlas Propagation and Segmentation (HMAPS), Learning Embeddings Atlas Propagation (LEAP), and NeuroQuant) in terms of 2-year changes in Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Sum of Boxes (CDR-SB). We modeled the implications for sample size, screen fail rates, and trial cost and duration. HCV based patient selection yielded reduced sample sizes (by ~40%-60%) and lower trial costs (by ~30%-40%) across a wide range of cut points. These results provide a guide to the choice of HCV cut point for amnestic MCI clinical trials, allowing an informed tradeoff between statistical and practical considerations. PMID- 24211009 TI - Role for the neurexin-neuroligin complex in Alzheimer's disease. AB - Synaptic damage is a critical hallmark of Alzheimer's disease, and the best correlate with cognitive impairment ante mortem. Synapses, the loci of communication between neurons, are characterized by signature protein combinations arrayed at tightly apposed pre- and post-synaptic sites. The most widely studied trans-synaptic junctional complexes, which direct synaptogenesis and foster the maintenance and stability of the mature terminal, are conjunctions of presynaptic neurexins and postsynaptic neuroligins. Fluctuations in the levels of neuroligins and neurexins can sway the balance between excitatory and inhibitory neurotransmission in the brain, and could lead to damage of synapses and dendrites. This review summarizes current understanding of the roles of neurexins and neuroligins proteolytic processing in synaptic plasticity in the human brain, and outlines their possible roles in beta-amyloid metabolism and function, which are central pathogenic events in Alzheimer's disease progression. PMID- 24211010 TI - Aging is associated with changes in the neural circuits underlying empathy. AB - Although the neurodevelopment of empathy from childhood to adolescence has been documented, no study has yet examined it across a life span aging perspective. Sixty-five healthy participants from 3 age groups (young, middle-aged, old) underwent functional magnetic resonance imaging while presented with visual stimuli depicting body parts being injured, either accidentally by oneself or intentionally by another, thus isolating pain and agency as 2 variables of interest. Older adults reported less dispositional emotional empathy as assessed by the interpersonal reactivity index, and their unpleasantness ratings were more sensitive to intentional harm. The response in anterior insula and anterior mid cingulate cortex to others' pain, indicative of emotional empathy, showed an age related decline, whereas the response in medial prefrontal cortex and posterior superior temporal sulcus to perceived agency did not change with age. Dynamic causal modeling demonstrated that their effective connectivity remained stable. The pattern of hemodynamic response was not related to regional gray matter volume loss. These findings suggest that the neural response associated with emotional empathy lessened with age, whereas the response to perceived agency is preserved. PMID- 24211011 TI - Prevalence, use and sale of contact lenses in Saudi Arabia: survey on university women and non-ophthalmic stores. AB - PURPOSE: To assess the prevalence and general knowledge of contact lens (CL) wear among women users and to examine the practice of CL dispensation by non ophthalmic stores. METHOD: One thousand four hundred and sixty-six female university students, between 16 and 31 years of age, and 1766 registered beauty stores in the region were randomly interviewed using self-administered questionnaires. The questions addressed general care/handling of CLs, CL case and solution hygiene practices by patients, the CL selection available in the shops, the type of instructions given to consumers, and who gives these instructions. RESULTS: The prevalence of CL use was 70.2% (1029/1466). Fifty percent were part time users of CLs, and cosmetic reasons were the major reason (63.3%) for CL use. Approximately 38.7% of the respondents used CL without consultation with an eye care practitioner. The main purchasing locations were optical shops (51%), beauty salons (38%), and pharmacies (11%). Concerning contact lens care, 89.4% of the respondents adequately washed their hands before handling CLs and 72.7% changed their solutions daily, while 7.7% admitted to occasional overnight wear of their CL and 27.6% sometimes shared their CLs with friends. Interestingly, 80.3% of the 1327 shops sold CLs with no prescription, and 61.4% gave no instructions to the patients during purchase. CONCLUSION: There is a high prevalence of CL use by female university students in Saudi Arabia, especially for cosmetic purposes. Although, there was good awareness with regard to general lens care practices, some users shared their lenses with friends, and the rate of sale of CLs without prescriptions in ordinary shops was high. PMID- 24211012 TI - References from Brazilian medical journals in national publications. AB - OBJECTIVE: To assess whether there is a preference for international journal citation to the detriment of national ones in ten Brazilian medical journals, in two different periods. METHODS: All references in the articles published in Arquivos Brasileiros de Oftalmologia, Revista Brasileira de Cirurgia Cardiovascular, Revista da Associacao Medica Brasileira, Sao Paulo Medical Journal, Arquivos Brasileiros de Endocrinologia e Metabologia, Clinics, Jornal Brasileiro de Pneumologia, Revista da Sociedade Brasileira de Medicina Tropical, Revista Brasileira de Psiquiatria e Acta Ortopedica Brasileira in the years 2011 and 2007 were analyzed, assessing the number of articles published in national and international journals. RESULTS: A total of 36,125 references from 1,462 articles published in the 10 aforementioned journals were analyzed. Of the total number, 4.242 (11.74%) were from Brazilian journals. There was no significant difference between the two analyzed periods. A total of 453 (30,98%) of the articles studied non-cited brazilian papers,and 81 (5.54%) articles had more Brazilian than international references. CONCLUSION: Of total references analyzed, 11.74% were related to articles published in Brazilian journals. This number, when compared to the percentage of Brazilian articles published in the medical area, demonstrates a good number of citations of national articles. PMID- 24211013 TI - Rebound effect of modern drugs: serious adverse event unknown by health professionals. AB - OBJECTIVE: Supported in the Hippocratic aphorism primum non nocere, the bioethical principle of non-maleficence pray that the medical act cause the least damage or injury to the health of the patient, leaving it to the doctor to assess the risks of a particular therapy through knowledge of possible adverse events of drugs. Among these, the rebound effect represents a common side effect to numerous classes of modern drugs, may cause serious and fatal disorders in patients. This review aims to clarify the health professionals on clinical and epidemiological aspects of rebound phenomenon. METHODS: A qualitative, exploratory and bibliographic review was held in the PubMed database using the keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor' and 'bisphosphonate'. RESULTS: The rebound effect occurs after discontinuation of numerous classes of drugs that act contrary to the disease disorders, exacerbating them at levels above those prior to treatment. Regardless of the disease, the drug and duration of treatment, the phenomenon manifests itself in a small proportion of susceptible individuals. However, it may cause serious and fatal adverse events should be considered a public health problem in view of the enormous consumption of drugs by population. CONCLUSION: Bringing together a growing and unquestionable body of evidence, the physician needs to have knowledge of the consequences of the rebound effect and how to minimize it, increasing safety in the management of modern drugs. On the other hand, this rebound can be used in a curative way, broadening the spectrum of the modern therapeutics. PMID- 24211014 TI - Chronic obstructive pulmonary disease in women exposed to wood stove smoke. AB - OBJECTIVE: To identify respiratory symptoms and COPD (forced vital capacity and forced expiratory volume in one second ratio < 0.70 and below the lower limit of normal) in non-smoking women with history of exposure to wood smoke of at least 80 hours-years. METHODS: One hundred sixty nonsmoking women were included. Demographic data and information about symptoms and other environmental exposures were collected. All women underwent spirometry and those with COPD also had their lung volumes measured. RESULTS: The COPD group had greater exposure in years to wood smoke (p = 0.043), greater length of rural residence (p = 0.042) and the same length of passive smoking (p = 0.297) and farm work (p = 0.985). Cough (69.8%), sputum (55.8%) and wheezing (67.4%) predominated in the COPD group (p < 0.001) compared to those without COPD (40.2%, 27.4%, 33, 3%, respectively). The COPD patients had mild to moderate obstructive disturbance and normal lung volumes, except that the residual volume and total lung capacity ratio (RV/TLC) > 0.40 in 45%, which correlated negatively with forced expiratory volume in one second (FEV1) and FEV1/vital forced capacity ratio (FEV1/FVC). CONCLUSION: Women with prolonged exposure to wood smoke had predominantly mild to moderate COPD. Those without COPD had a high prevalence of chronic respiratory symptoms, justifying clinical and spirometric monitoring. PMID- 24211015 TI - Arteriographic findings in diabetic and non-diabetic with critical limb ischemia. AB - OBJECTIVE: To compare angiographic findings of diabetic and non-diabetic patients with critical limb ischemia. METHODS: We included 161 patients with infrainguinal critical limb ischemia (CLI). We evaluated the clinical and arteriographic (number and presence of opacification of leg arteries) of the two groups of patients. Statistical analysis was performed using EPI-INFO. RESULTS: Most patients were category 5 of Rutherford's Classification and had femoropopliteal disease. Seventy-two percent of non-diabetic and 67% of diabetic had opacification of the fibular artery (p = 0.25), this is the most present artery in both groups. Diabetic patients had less opacification of the posterior tibial artery in the univariate analysis (29% vs. 47%, p = 0.008). But only female sex showed a significant risk for the absence of the posterior tibial artery in logistic regression (OR = 2.6; p = 0.01). CONCLUSION: The peroneal artery was the most frequently artery in angiograms of diabetic and non-diabetic patients with CLI. Diabetic and non-diabetic patients did not differ in angiographic findings of the leg. PMID- 24211016 TI - Defining the anti-inflammatory activity of a potent myxomaviral chemokine modulating protein, M-T7, through site directed mutagenesis. AB - Viral chemokine modulating proteins provide new and extensive sources for therapeutics. Purified M-T7, a poxvirus-derived secreted immunomodulatory protein, reduces mononuclear cell invasion and atheroma in rodent models of angioplasty injury as well as aortic and renal transplant, improving renal allograft survival. M-T7 is a rabbit species-specific interferon gamma receptor (IFNgammaR) homolog, but also inhibits chemokine/glycosaminoglycan (GAG) interactions for C, CC and CXC chemokines, with cross-species specific inhibitory activity. M-T7 anti-atheroma activity is blunted in GAG deficient mouse aortic transplants, but not in CC chemokine receptor deficient transplants, supporting M T7 interference in chemokine/GAG interactions as the basis of the atheroma inhibitory activity. We have assessed point mutants of M-T7 both in vivo in a mouse angioplasty model and in vitro in tissue culture and binding assays, in order to better define the primary mechanism of anti-atheroma activity. Of these M-T7 mutants, the R(171)E and E(209)I M-T7 mutants lost inhibitory activity for plaque growth in hyperlipidemic ApoE(-/-) mice after angioplasty injury and R(171)E, moreover, greatly exacerbated plaque growth and inflammation. F(137)D retained some inhibitory activity for plaque growth. In contrast, for cell migration assays, M-T7-His6X, F(137)D, R(171)E, and E(209)I all inhibited CC chemokine (RANTES) mediated cell migration. For the ligand binding assays, R(171)E and E(209)I had significantly reduced binding to RANTES and IFNgamma, whereas F(137)D retained wild-type binding activity. Heparin treatment further reduced RANTES binding of all three M-T7 mutants. In summary, point mutations of M-T7, R(171)E and E(209)I, exhibited reduced anti-inflammatory properties in vivo after mouse angioplasty with a loss of in vitro binding to RANTES and IFNgamma, indicating these point mutations partially disrupt M-T7 ligand-binding activities. Unexpectedly, the M-T7 mutants all retained inhibitory activity for human monocyte THP-1 cell migration ex vivo, suggesting additional inhibitory properties against human monocyte THP-1 cells that are independent of chemokine inhibition. PMID- 24211018 TI - Suggestions for a Web based universal exchange and inference language for medicine. AB - Mining biomedical and pharmaceutical data generates huge numbers of interacting probabilistic statements for inference, which can be supported by mining Web text sources. This latter can also be probabilistic, in a sense described in this report. However, the diversity of tools for probabilistic inference is troublesome, suggesting a need for a unifying best practice. Physicists often claim that quantum mechanics is the universal best practice for probabilistic reasoning. We discuss how the Dirac notation and algebra suggest the form and algebraic and semantic meaning of XML-like Web tags for a clinical and biomedical universal exchange language formulated to make sense directly to the eye of the physician and biomedical researcher. PMID- 24211017 TI - Detailed assessments of childhood adversity enhance prediction of central obesity independent of gender, race, adult psychosocial risk and health behaviors. AB - OBJECTIVE: This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of "modifiable" risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities * severity * chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. MATERIALS/METHODS: 210 Black/African Americans and White/European Americans, mean age=45.8; +/-3.3 years, were studied cross sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). RESULTS: Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. CONCLUSIONS: Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. PMID- 24211019 TI - Truncated and constrained helical analogs of antimicrobial esculentin-2EM. AB - Esculentin-2EM is a 37-residue, cationic, amphipathic, alpha-helical antimicrobial peptide isolated from a Korean frog, Glandirama emeljanovi. Many studies revealed that truncation of this peptide results in substantial decreases in its antimicrobial activity. Lee and his colleagues have recently reported that a 23-residue esculentin-2EM analog containing a tryptophanyl substitution at position 16 showed a significant recovery of the antimicrobial activity of the parent peptide. Here we report a new series of 15-residue esculentin-2EM analogs which are constrained into an alpha-helical conformation via an oct-4-enyl cross link. The resulting 'stapled' derivatives displayed remarkable increases not only in antimicrobial activity but also in helical content and protease resistance compared to Lee's original 23-residue esculentin-2EM analog. The preliminary data obtained in this work strongly supports the potential of our strategy for the development of a new class of peptide antibiotics. PMID- 24211020 TI - Chlorophenylpiperazine analogues as high affinity dopamine transporter ligands. AB - Selective sigma2 ligands continue to be an active target for medications to attenuate the effects of psychostimulants. In the course of our studies to determine the optimal substituents in the sigma2-selective phenyl piperazines analogues with reduced activity at other neurotransmitter systems, we discovered that 1-(3-chlorophenyl)-4-phenethylpiperazine actually had preferentially increased affinity for dopamine transporters (DAT), yielding a highly selective DAT ligand. PMID- 24211021 TI - Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers. AB - Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1 MUM). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest. PMID- 24211022 TI - Discovery of a potent respiratory syncytial virus RNA polymerase inhibitor. AB - Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date. PMID- 24211023 TI - Development and preliminary validation of a new scale to assess functional ability of older population in India. AB - Identifying the decline in functional ability and preventing disability is the critical element of the quality of life of an old age. However, the lack of contextual scale to assess the decline in functional capacity is a major issue. Objective of this study is to design the functional ability assessment scale for elderly people in India and test its psychometric properties. Random sample of 659 individuals above 60 years of age from western part of India was recruited. This paper outlines the construction, reliability and validity of a newly developed 14 item scale named as Pune-Functional Ability Assessment Tool (Pune FAAT). The factors were extracted using the principal component analysis. Two factor-structure of scale was accepted after applying the K1 rule, scree plot and parallel analysis method. The two factor structure yielded variance of 64.4%. The psychometric properties of the scale were examined using confirmatory factor analysis. The scale has an excellent reliability (Cronbach's alpha 0.928) and very good test-retest reliability (r=0.884). Each subscale demonstrated good internal consistency (Subscale I - Cronbach's alpha 0.938 and Subscale II - Cronbach's alpha 0.762). Excellent convergent validity with Standford's health assessment questionnaire (r=0.959). Discriminant validity was very good as FAAT index showed significant difference in young adults (mean+/-SD 1.11+/-0.24) and older adults (mean+/-SD 1.69+/-0.70). This new measure is a potentially valuable research tool for investigating older adult's functional ability to perform basic and complex daily activities. PMID- 24211024 TI - Older person behavioral and psychological symptoms (BPS) and functional limitations mediate the association between older person cognitive impairment and depressive symptoms in the caregiver. AB - We assess for the mediation of the association between older person cognitive impairment and caregiver depressive symptoms through older person BPS and functional limitations, and whether the mediation varies by caregiver-older person relationship (spouse/adult child). Data for 1111 older person (aged 75+ with activity of daily living (ADL) limitation)-caregiver dyads from Singapore were used. The outcome variable was dichotomous (caregiver clinically significant depressive symptoms [CSDS]: yes/no) in the primary analysis and continuous (caregiver depressive symptoms score) in the sensitivity analysis. The causal steps approach assessed for the mediation of the association between older person cognitive impairment (yes/no) and the outcome variable through the two potential mediators. A bootstrapping approach calculated point estimates and confidence intervals (CIs) of the indirect (~mediated) effects. Variation of the indirect effects by caregiver-older person relationship was also assessed. In the primary analysis, the causal steps approach supported older person BPS and functional limitations as mediators. The bootstrapping approach confirmed both as significant mediators, though BPS (indirect effect odds ratio (OR) 1.32 [95% bootstrap CI 1.19,1.48]; %mediation: 70.6%) was a stronger mediator than functional limitations (1.04 [1.01,1.11]; %mediation: 11.5%). Variation of the indirect effects by caregiver-older person relationship was not supported. Results of the sensitivity analysis confirmed these results. We conclude that while caring for an older person with cognitive impairment is detrimental for the caregiver's mood, management of associated BPS and functional limitations, especially the former, among such older persons may reduce depressive symptoms among their caregivers. Spouse as well as adult child caregivers benefit. PMID- 24211025 TI - Reduction of cognitive concerns of anxiety sensitivity is uniquely associated with reduction of PTSD and depressive symptoms: a comparison of civilians and veterans. AB - PTSD and comorbid depression are common among civilians and veterans, resulting in substantial impairment. Anxiety sensitivity (AS) may be a common malleable vulnerability factor for PTSD and depression. The AS cognitive concerns subscale is most strongly related to symptoms of PTSD and depression, and thus, may be an efficient route to reduce these symptoms. The current study evaluated a brief computerized intervention targeting AS cognitive concerns. Specifically, we evaluated whether reduction in AS cognitive concerns was associated with reduction in symptoms of PTSD and depression. Also, we evaluated whether there was a significant difference between civilians and veterans in response to the intervention. The single session intervention utilized psychoeducation and interoceptive exposure to target AS cognitive concerns. This intervention was compared to a health information condition among a sex-matched sample of civilians and veterans with elevated AS cognitive concerns (N = 56). Reduction in AS cognitive concerns over one month was uniquely associated with reduction in PTSD and depressive symptoms in the same time frame. There were no significant differences between civilians and veterans in response to the intervention suggesting the intervention has efficacy for both groups. Treatment implications are discussed. PMID- 24211026 TI - The use of antidepressant medication in pregnancy. AB - The use of antidepressant medications during pregnancy has stimulated much professional and public debate. As a consequence, considerable data on the reproductive safety of antidepressants has been generated that exceeds the available information for most, if not all, other classes of medications that may be used in the perinatal period. Despite progress to date, definitive conclusions are limited by the methodological issues inherent to clinical research involving illness versus treatment effects in pregnancy. A notable shortcoming is the limited discussion of statistically significant (a mathematical determination) versus clinically significant (incorporation of incidence and effect sizes into practical relevance). Research emphasises completing an individualised 'risk benefit' assessment, which is a laudable goal but falls short in providing succinct practical guidelines that includes the key educational points for patients. In this chapter, we focus on areas in which the preponderance of data are consistent, and there is concordance with the preclinical literature to generate a practical approach for antidepressant use in pregnancy. PMID- 24211027 TI - Longitudinal study of remission among older adults with schizophrenia spectrum disorder. AB - OBJECTIVE: Although studies have found that as many as half of older community dwelling adults with schizophrenia were in symptomatic remission, these findings had been based on cross-sectional data. This study examines longitudinal changes in symptom remission rates and predictors of remission. METHODS: The original sample consisted of 250 persons with schizophrenia spectrum disorders aged 55 and over living in New York City who developed the disorder before age 45. Data on 104 follow-up interviews are presented. Mean follow-up was 54 months (range: 12 116 months); mean age was 61 years, 55% were male, and 55% were white. A modified version of the Remission in Schizophrenia Working Group criteria was used for determining remission status. RESULTS: There was a nonsignificant decline in the percentage attaining remission (49% baseline, 40% follow-up); 25% were in remission at both assessments, 35% were not in remission at either assessment, 25% went from remission to nonremission, and 16% went from nonremission to remission. Four significant baseline predictors of remission were found at follow up: higher community integration, greater number of entitlements, fewer psychotropic medications, and lower frequency of psychiatric services. Baseline remission status predicted having more total contacts at follow-up. CONCLUSION: Older adulthood is not necessarily a quiescent period, and there is considerable fluctuation in remission status. Two social variables-community integration and entitlements-predicted remission on follow-up, thus suggesting social interventions may be especially useful strategies for this population. PMID- 24211029 TI - Increased risk among older veterans of prescribing psychotropic medication in the absence of psychiatric diagnoses. AB - OBJECTIVE: This study uses Veterans Health Administration (VHA) pharmacy and encounter claims to evaluate the use of psychotropic medications without a psychiatric diagnosis across age groups. METHODS: National VHA administrative data for fiscal year 2010 (FY2010) were used to identify all veterans who filled a prescription for at least one psychotropic medication from VHA (N = 1.85 million). Bivariate and multivariate analyses were used to compare the proportion of these veterans without any psychiatric diagnosis, across age groups, adjusting for possible medical indications. Analyses were repeated for six different classes of psychotropic medications and comparing mental health utilizers and non mental health utilizers. Comparisons were made to prescribing of HIV and diabetes medications without an indicated diagnosis. RESULTS: Of all VHA patients prescribed a psychotropic medication in FY2010, 30% had no psychiatric diagnosis, with highest proportions among veterans ages 65-85. This practice was most frequent among nonmental health utilizers and far more prevalent for psychotropic medications than for HIV or diabetes medications. Logistic regression analysis found that age greater than 65 was the strongest predictor of being prescribed a psychotropic without a psychiatric diagnosis. Adjustment for possible medical use of psychotropics and overall medical comorbidity did not substantially alter these trends. CONCLUSION: Older veterans, especially those not using specialty mental healthcare, are more likely to be prescribed psychotropic medications in the absence of a psychiatric diagnosis, perhaps representing unnecessary use, under-diagnosis of mental illness, or incomplete documentation. PMID- 24211028 TI - Depressive symptoms, symptom dimensions, and white matter lesion volume in older adults: a longitudinal study. AB - OBJECTIVE: White matter lesions (WMLs) are associated with depressive symptoms in older adults. However, it is not clear whether different symptom dimensions of depression have distinct associations with WMLs. The authors assessed the longitudinal relationships of the Center for Epidemiologic Studies Depression Scale (CES-D) total score and subscale scores with WML volume in the Baltimore Longitudinal Study of Aging. METHODS: Using a prospective observational design, the authors examined WML volume and depressive symptoms at 1- to 2-year intervals for up to 9 years in 116 dementia-free participants (mean age: 68.78 +/- 7.68). At each visit, depressive symptoms were measured with the CES-D and WML volumes were quantified from structural magnetic resonance imaging scans. RESULTS: Higher CES-D full-scale scores were associated with greater WML volume and with a faster rate of volume increases over time in women, especially at older ages. Higher depressed mood and somatic symptoms subscale scores were associated with greater increases in WML volume over time at older ages. In men, depressed mood and somatic symptoms were associated with larger WML volume at baseline. CONCLUSION: Findings confirm an association between WMLs and depressive symptoms and suggest that depressed mood and somatic symptoms may be stronger predictors of depression related brain changes than lack of well-being. Age and sex may moderate the relationships between depressive symptoms and WMLs. Understanding particular symptom dimensions of depressive symptoms has implications for treatment and may lead to targeted interventions and more precise knowledge of mechanisms underlying depression. PMID- 24211030 TI - Enantioseletive bioaccumulation and metabolization of diniconazole in earthworms (Eiseniafetida) in an artificial soil. AB - Degradation and enantioselective bioaccumulation of diniconazole in earthworms (Eiseniafetida) in artificial soil was investigated using liquid chromatography tandem mass spectrometry (LC-MS/MS) method under laboratory condition. Three exposure concentrations (1 mg/kg, 10 mg/kg and 25 mg/kg) of diniconazole in soil (dry weight) to earthworms were used. The uptake kinetics fitted the first-order kinetics well. The bioaccumulation factors (BAF) of R, S isomers were 6.6046 and 8.5115 in 25 mg/kg dose exposure, 2.6409 and 2.9835 in 10mg/kg dose exposure, 1.7784 and 2.0437 in 1 mg/kg dose exposure, respectively. Bioaccumulation of diniconazole in earthworm tissues was enantioselective with a preferential accumulation of S-diniconazole and the enantiomer fractions were about 0.45-0.50 in all three level dose exposures. In addition, it was obvious that both R diniconazole and S-diniconazole had bioaccumulation effect in earthworm. Diniconazole was metabolized to 1,2,4-triazole, (E)-3-(1H-1,2,4-triazol-1-yl) acrylaldehyde, (E, S)-4-(2, 4-dichlorophenyl)-2, 2-dimethyl-5-(1H-1,2,4-triazol-1 yl)pent-4-ene-1,3-diol, and (E)-4-(2, 4-dichlorophenyl)-3-hydroxy-2,2-dimethyl-5 (1H-1,2,4-triazol-1-yl) pent-4-enoic acid in earthworms; the metabolites of 1,2,4 triazole and (E)-3-(1H-1,2,4-triazol-1-yl)acrylaldehyde could be detected in soil as well. PMID- 24211031 TI - [Choice of career by French medical students after the national ranking exam in 2012]. AB - PURPOSE: Since 2011, the French medical students ranked after a national ranking exam (NRE) are making their career choice among 11 disciplines detailing the chosen one. Before 2011, this precise choice was unknown. Our work is the first descriptive study of French medical students choice of career after the NRE, precising the medical specialty chosen and the city of practical formation. METHODS: We analyzed the Excel((r)) file transmitted by the 'Agence regionale de sante d'Aquitaine' once students choice done after the 2012 NRE. A median range analysis was made for disciplines and city formation choices. For medical and surgery specialties, the analysis was compared to regional medical densities. RESULTS: According to the median national choice, the first sixth disciplines chosen are ophthalmology, nephrology, internal medicine, radiology, cardiology and dermatology. Women are more attracted by medical gynecology, obstetrics, pediatrics, or dermatology; men mostly by neurosurgery, general surgery, nuclear medicine or cardiology. The most rated cities of formation according to their national median range of choice are Lyon, Montpellier and Paris. A majority of students (59 %) moved to another city to obtain the desired specialty. Among general practitioners, 56 % of students stayed in the city where they had been trained. PERSPECTIVES: Our study may provide concrete objectives for French medical students accomplishing their second cycle of medical studies, as well as supplemental data for French medical demographic management. PMID- 24211032 TI - Building a picture: Prioritisation of exotic diseases for the pig industry in Australia using multi-criteria decision analysis. AB - Diseases that are exotic to the pig industry in Australia were prioritised using a multi-criteria decision analysis framework that incorporated weights of importance for a range of criteria important to industry stakeholders. Measurements were collected for each disease for nine criteria that described potential disease impacts. A total score was calculated for each disease using a weighted sum value function that aggregated the nine disease criterion measurements and weights of importance for the criteria that were previously elicited from two groups of industry stakeholders. One stakeholder group placed most value on the impacts of disease on livestock, and one group placed more value on the zoonotic impacts of diseases. Prioritisation lists ordered by disease score were produced for both of these groups. Vesicular diseases were found to have the highest priority for the group valuing disease impacts on livestock, followed by acute forms of African and classical swine fever, then highly pathogenic porcine reproductive and respiratory syndrome. The group who valued zoonotic disease impacts prioritised rabies, followed by Japanese encephalitis, Eastern equine encephalitis and Nipah virus, interspersed with vesicular diseases. The multi-criteria framework used in this study systematically prioritised diseases using a multi-attribute theory based technique that provided transparency and repeatability in the process. Flexibility of the framework was demonstrated by aggregating the criterion weights from more than one stakeholder group with the disease measurements for the criteria. This technique allowed industry stakeholders to be active in resource allocation for their industry without the need to be disease experts. We believe it is the first prioritisation of livestock diseases using values provided by industry stakeholders. The prioritisation lists will be used by industry stakeholders to identify diseases for further risk analysis and disease spread modelling to understand biosecurity risks to this industry. PMID- 24211033 TI - The National Prostate Cancer Audit - introducing a new generation of cancer audit. PMID- 24211034 TI - Prevalence of restless legs syndrome in patients with chronic pain in Maputo, Mozambique. AB - OBJECTIVES: Because there is only one study to our knowledge on the prevalence of restless legs syndrome (RLS) in sub-Saharan Africa and RLS is more common in patients with some pain syndromes, we aimed to determine the prevalence of RLS in a population with chronic pain in Maputo, Mozambique. METHODS: Our study was conducted in the Pain Unit of the Central Hospital of Maputo, Mozambique. Patients were individually interviewed by a neurologist, and only those fulfilling the criteria were included. After collection of demographic data and pain features, the patients answered the screening questions regarding RLS. RESULTS: A total of 123 patients with pain were interviewed. Five individuals were excluded. RLS was found in eight (6.77%) of 118 patients. The mean age of the eight patients with RLS was 54.6years. Five patients (62.5%) were women and six (75%) were black individuals. Seven (87.5%) patients were diagnosed with neuropathic pain; one of them had AIDS and another one (12.5%) had orthopedic pain. The presence of hypertension and neuropathies was more frequent in the RLS group. CONCLUSION: Despite the secondary causes involved, we believe that it is relevant to report the RLS prevalence detected in our study. PMID- 24211035 TI - Screening for sleep dysfunction after traumatic brain injury. AB - Numerous studies on the high prevalence of sleep disorders in individuals with traumatic brain injury (TBI) have been conducted in the past few decades. These disorders can accentuate other consequences of TBI, negatively impacting mood, exacerbating pain, heightening irritability, and diminishing cognitive abilities and the potential for recovery. Nevertheless, sleep is not routinely assessed in this population. In our review, we examined the selective screening criteria and the scientific evidence regarding screening for post-TBI sleep disorders to identify gaps in our knowledge that are in need of resolution. We retrieved papers written in the English-language literature before June 2012 pertinent to the discussion on sleep after TBI found through a PubMed search. Within our research, we found that sleep dysfunction is highly burdensome after TBI, treatment interventions for some sleep disorders result in favorable outcomes, sensitive and specific tests to detect sleep disorders are available, and the cost-effectiveness and sustainability of screening have been determined from other populations. The evidence we reviewed supports screening for post-TBI sleep dysfunction. This approach could improve the outcomes and reduce the risks for post-TBI adverse health and nonhealth effects (e.g., secondary injuries). A joint sleep and brain injury collaboration focusing on outcomes is needed to improve our knowledge. PMID- 24211036 TI - Whole-body MRI vs. CT for staging lymphoma: patient experience. AB - OBJECTIVE: To assess and compare patient experience of whole-body magnetic resonance imaging (MRI) to that of computed tomography (CT) for staging newly diagnosed lymphoma. MATERIALS AND METHODS: A total of 36 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI and CT for staging purposes. Patients were asked to fill in a short questionnaire with regard to the burden and experience of the examination on a Likert scale (range 1-4). Wilcoxon signed rank tests were used to determine statistically significant differences in patient (dis)comfort between the two examinations. RESULTS: Patients reported to be significantly (P=0.007) less worried before undergoing whole-body MRI compared to CT. Patients also experienced whole-body MRI as significantly (P=0.010) less unpleasant and felt significantly (P=0.003) better shortly after the scan. The necessary preparations before CT scanning (i.e. insertion of intravenous line, drinking of contrast fluid), which are not required for whole-body MRI, were reported to be a considerable burden. CONCLUSION: In this study in patients with newly diagnosed lymphoma, whole-body MRI was experienced as a more patient friendly technique than CT. PMID- 24211037 TI - Advanced computed tomographic anatomical and morphometric plaque analysis for prediction of fractional flow reserve in intermediate coronary lesions. AB - OBJECTIVE: To determine the application of advanced coronary computed tomography angiography (CCTA) plaque analysis for predicting invasive fractional flow reserve (FFR) in intermediate coronary lesions. METHODS: Sixty-one patients with 71 single intermediate coronary lesions (>= 50-80% stenosis) on CCTA prospectively underwent coronary angiography and FFR. Advanced anatomical and morphometric plaque analysis was performed based on CCTA data set to determine optimal criteria for significant flow impairment. A significant stenosis was defined as FFR <= 0.80. RESULTS: FFR averaged 0.85 +/- 0.09, and 19 lesions (27%) were functionally significant. FFR correlated with minimum lumen area (MLA) (r=0.456, p<0.001), minimum lumen diameter (MLD) (r=0.326, p=0.006), reference lumen diameter (RLD) (r=0.245, p=0.039), plaque burden (r=-0.313, p=0.008), lumen area stenosis (r=-0.305, p=0.01), lesion length (r=-0.692, p<0.001), and plaque volume (r=-0.668, p<0.001). There was no relationship between FFR and CCTA morphometric plaque parameters. By multivariate analysis the independent predictors of FFR were lesion length (beta=-0.581, p<0.001), MLA (beta=0.360, p=0.041), and RLD (beta=-0.255, p=0.036). The optimal cutoffs for lesion length, MLA, MLD, RLD, and lumen area stenosis were >18.5mm, <= 3.0mm(2), <= 2.1mm, <= 3.2mm, and >69%, respectively (max. sensitivity: 100% for MLA, max. specificity: 79% for lumen area stenosis). CONCLUSIONS: CCTA predictors for FFR support the mathematical relationship between stenosis pressure drop and coronary flow. CCTA could prove to be a useful rule-out test for significant hemodynamic effects of intermediate coronary stenoses. PMID- 24211038 TI - Purification, characterization, molecular cloning, and extracellular production of a novel bacterial glycerophosphocholine cholinephosphodiesterase from Streptomyces sanglieri. AB - A novel metal ion-independent glycerophosphocholine cholinephosphodiesterase (GPC CP) of Streptomyces sanglieri was purified 53-fold from culture supernatant with 1.1% recovery (583 U/mg-protein). The enzyme functions as a monomer with a molecular mass of 66 kDa. The gene encoding the enzyme consists of a 1941-bp ORF that produces a signal peptide of 38 amino acids for secretion and a 646 amino acid mature protein with a calculated molecular mass of 70,447 Da. The maximum activity was found at pH 7.2 and 40 degrees C. The enzyme hydrolyzed glycerol-3 phosphocholine (GPC) over a broad temperature range (37-60 degrees C) and within a narrow pH range near pH 7. The enzyme was stable at 50 degrees C for 30 min and between pH 5-10.5. The enzyme exhibited specificity toward GPC and glycerol-3 phosphoethanolamine and hydrolyzed glycerol-3-phosphate and lysophosphatidylcholine. However, the enzyme showed no activity toward any diacylglycerophospholipids and little activity toward other glycerol-3 phosphodiesters and lysophospholipids. The enzyme was not inhibited in the presence of 2 mM SDS and Mg(2+); however, Cu(2+), Zn(2+), and Co(2+) remarkably inhibited activity. Enzyme activity was also slightly enhanced by Ca(2+), Na(+), EDTA, DTT, and 2-mercaptoethanol. During the hydrolysis of GPC at 37 degrees C and pH 7.2, apparent Vmax and turnover number (kcat) were determined to be 24.7 MUmol min(-1) mg-protein(-1) and 29.0 s(-1), respectively. The apparent Km and kcat/Km values were 1.41 mM and 20.6 mM(-1) s(-1), respectively. GPC hydrolysis by GPC-CP might represent a new metabolic pathway for acquisition of a phosphorus source in actinomycetes. PMID- 24211040 TI - Reasons for rarity of Th17 cells in inflammatory sites of human disorders. AB - T helper 17 (Th17) cells have been reported to be responsible for several chronic inflammatory diseases. However, a peculiar feature of human Th17 cells is that they are very rare in the inflammatory sites in comparison with Th1 cells. The first reason for this rarity is the existence of some self-regulatory mechanisms that limit their expansion. The limited expansion of human Th17 cells is related to the retinoic acid orphan (ROR)C-dependent up-regulation of the interleukin (IL)-4 induced gene 1 (IL4I1), which encodes for a l-phenylalanine oxidase, that has been shown to down-regulate CD3zeta expression in T cells. This results in abnormalities of the molecular pathway which is responsible for the impairment of IL-2 production and therefore for the lack of cell proliferation in response to T cell receptor (TCR) signalling. IL4I1 up-regulation also associates with the increased expression of Tob1, a member of the Tob/BTG anti-proliferative protein family, which is involved in cell cycle arrest. A second reason for the rarity of human Th17 cells in the inflammatory sites is their rapid shifting into the Th1 phenotype, which is mainly related to the activity of IL-12 and TNF-alpha. We have named these Th17-derived Th1 cells as non-classic because they differ from classic Th1 cells for the expression of molecules specific for Th17 cells, such as RORC, CD161, CCR6, IL4I1, and IL-17 receptor E. This distinction may be important for defining the respective pathogenic role of Th17, non-classic Th1 and classic Th1 cells in many human inflammatory disorders. PMID- 24211039 TI - The plasticity of human Treg and Th17 cells and its role in autoimmunity. AB - CD4(+) T helper cells are a central element of the adaptive immune system. They protect the organism against a wide range of pathogens and are able to initiate and control many immune reactions in combination with other cells of the adaptive and the innate immune system. Starting from a naive cell, CD4(+) T cells can differentiate into various effector cell populations with specialized function. This subset specific differentiation depends on numerous signals and the strength of stimulation. However, recent data have shown that differentiated CD4(+) T cell subpopulations display a high grade of plasticity and that their initial differentiation is not an endpoint of T cell development. In particular, FoxP3(+) regulatory T cells (Treg) and Th17 effector T cells demonstrate a high grade of plasticity, which allow a functional adaptation to various physiological situations during an immune response. However, the plasticity of Treg and Th17 cells might also be a critical factor for autoimmune disease. Here we discuss the recent developments in CD4(+) T cell plasticity with a focus on Treg and Th17 cells and its role in human autoimmune disease, in particular multiple sclerosis (MS). PMID- 24211042 TI - Delayed presentation of acute aortic syndrome. PMID- 24211041 TI - Induction and stability of the anergic phenotype in T cells. AB - One of the mechanisms that are in place to control the activation of mature T cells that bear self-reactive antigen receptors is anergy, a long-term state of hyporesponsiveness that is established in T cells in response to suboptimal stimulation. T cells receive signals that result not only from antigen recognition and costimulation but also from other sources, including cytokine receptors, inhibitory receptors or metabolic sensors. Integration of those signals will determine T cell fate. Under conditions that induce anergy, T cells activate a program of gene expression that leads to the production of proteins that block T cell receptor signaling and inhibit cytokine gene expression. In this review we will examine those signals that determine functional outcome following antigen encounter, review current knowledge of the factors that ensure signaling inhibition and epigenetic gene silencing in anergic cells and explore the mechanisms that lead to the reversal of anergy and the reacquisition of effector functions. PMID- 24211043 TI - Polio emergence in Syria and Israel endangers Europe. PMID- 24211044 TI - Responding to the Syrian crisis: the needs of women and girls. PMID- 24211046 TI - Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test. AB - An outbreak of human leishmaniasis was confirmed in the southwest of the province of Madrid, Spain, between July 2009 and December 2012. Incidence of Leishmania infection in dogs was unchanged in this period, prompting a search for alternative sylvatic infection reservoirs. We evaluated exposure to Leishmania in serum samples from animals in the area with an indirect immunofluorescence test (IFAT). Using promastigotes from six culture passages and a 1/25 threshold titer, we found anti-Leishmania infantum seroreactivity in 9.3% of cats (4 of 43), 45.7% of rabbits (16/35) and 74.1% of hares (63/85). Use of promastigotes from >10 in vitro passages resulted in a notably IFAT lower titer, suggesting antigenic changes during extended culture. Postmortem inspection of seropositive animals showed no clinical signs of infection. The results clearly suggest that asymptomatic hares were the main reservoir in the outbreak, and corroborate IFAT as a sensitive serological surveillance method to detect such cryptic Leishmania infections. PMID- 24211045 TI - Coincidental vascular anomalies at the foramen magnum: dural arteriovenous fistula and high flow aneurysm on perimedullary fistula. AB - We report the case of a 59-year-old woman admitted for a sudden headache due to a subarachnoid haemorrhage. On CT scan, the clots predominated into the posterior fossa without high-density in the sylvian or interhemispheric fissures. The vertebral angiography revealed a dural arteriovenous fistula at the foramen magnum associated to an aneurysm of the cervical anterior spinal artery. Due to the high rebleeding risk of a dural shunt, we proposed curative treatment using microsurgical interruption of the intradural draining vein. On the postoperative angiography at 15-day follow-up, the 2 malformations were corrected and the outcome at 6 months was excellent. Based on the literature, we assess this exceptional association and suggest its possible management. PMID- 24211047 TI - Factors affecting stress experienced by surrogate decision makers for critically ill patients: implications for nursing practice. AB - OBJECTIVES: This study explores surrogate decision-makers' (SDMs) challenges making decisions related to the care of patients in critical care, to (1) characterise the SDM stress, (2) identify personal, social, care-related factors influencing stress and (3) consider implications of findings to improving critical care practice. METHODOLOGY: Semi-structured interviews were conducted with SDMs of critically ill patients receiving care in two tertiary care institutions. Transcripts were analysed using a grounded theory approach. Domains explored were: stress characteristics, stress mitigators, coping strategies, social networks, SDM decision-making role, decision-making concordance, knowledge of patient's preferences, experience with provider team, SDM-provider communication, patient outcome certainty. MAIN OUTCOMES: We interviewed 34 SDMs. Most were female and described long-term relationships with patients. SDMs described the strain of uncertain outcomes and decision-making without clear, consistent information from providers. Decision-making anxiety was buffered by SDMs' active engagement of social networks, faith and access to clear communication from providers. CONCLUSION: Stress is a very real factor influencing SDMs confidence and comfort making decisions. These findings suggest that stress can be minimised by improving communication between SDMs and medical providers. Nurses' central role in the ICU makes them uniquely poised to spearhead interventions to improve provider-SDM communication and reduce SDM decision-making anxiety. PMID- 24211048 TI - Providing critical care patients with a personalised discharge summary: a questionnaire survey and retrospective analysis exploring feasibility and effectiveness. AB - OBJECTIVES: This paper reports on the potential value and feasibility of providing patients with a personalised discharge summary of their critical care stay. DESIGN AND METHODS: Fifty-one patient discharge summaries, written by nurses during a randomised controlled trial, were retrospectively analysed for readability, structure and quality. A questionnaire survey completed by trial patients (n=42), their relatives (n=21) and nurses (n=170) explored user experience and feasibility. Quantitative questionnaire data were analysed descriptively and inferentially; qualitative data were subjected to content analysis. RESULTS: Most completed summaries achieved at least an average readability score and were of an acceptable quality. Motivation, time constraints and competing priorities were identified as key barriers to writing an effective summary; however, in the majority of cases, writing them had taken less than 15 minutes. Questionnaire data support that patient discharge summaries can help patients, relatives and ward nurses better understand and patients accept, what happened in critical care. CONCLUSION: Patient discharge summaries are likely to be a useful adjunct to existing discharge information, but further work is required to determine when and how they should be provided. With appropriate training and support, it is feasible for nurses to write discharge summaries in a busy critical care environment. PMID- 24211049 TI - Attitudes of legal guardians in the ICU - a qualitative report. AB - Decision-making in intensive care units (ICUs) is often made by surrogates, since patients are unconscious or incompetent. In Israel, Legal Guardians (LGs), appointed by the court, are required to make these decisions. OBJECTIVE: To qualitatively assess the attitudes of LGs required to make decisions on behalf of their relatives. RESEARCH DESIGN: Demographic and semi-structured questionnaires were used to assess the attitudes of LGs regarding difficulties, positive aspects and areas for improvement with regard to surrogate decision-making. The study sampled sixty-four LGs in two large Israeli hospitals. After reading and analysing the responses provided by the LGs, the authors categorised the pertinent topics raised using a thematic analysis. RESULTS: Themes were: bureaucratic and legal issues, unclear or unknown patient preferences and fear of outcomes. Family and medical staff support was stated as the most beneficial. Suggestions for improvement included alleviation of bureaucracy and improved communication with the medical staff. CONCLUSIONS: The importance of communication and bureaucratic difficulties, making the best decision for the patient and uncertainty regarding decision outcomes were found to be important issue for the LGs. The healthcare team should try and alleviate some of these burdens, mostly by improving communication with relatives, stressing and educating the importance of advance directives. Reporting the problems found in the decision making process of LGs to the legislators in order to revise and simplify the current legal requirements is advised. PMID- 24211051 TI - Gastrocnaemius-propeller extended miocutanous flap: a new chimaeric flap for soft tissue reconstruction of the knee. AB - PURPOSE: Soft tissue defects involving the anterior aspect of the knee are a frequent finding in a number of pathological conditions. The aim of this article is to describe a new pedicled flap consisting of a conventional medial gastrocnaemius muscle flap associated with a propeller flap based on a perforator of the medial sural artery. MATERIAL AND METHODS: Five males ranging in age between 26 and 72 years underwent a reconstruction of the soft tissue of the knee by means of the described procedure. Three patients sustained complex tissue loss subsequent to high-energy trauma; two losses were due to septic complications after elective knee surgery. RESULTS: Four flaps survived allowing adequate proximal tibial metaphysis and patella coverage. One patient underwent early above-the-knee amputation due to life-threatening septicaemia. DISCUSSION: The described chimaera flap consists of a medial gastrocnaemius flap with a skin paddle that is elevated on a perforator of the medial sural artery and then rotated according to the propeller flaps' principles. It provides effective coverage of large soft tissue defects of the knee. In the authors' experience, the propeller flap portion proved to be particularly useful to cover the patella, while the muscle flap was used to cover the proximal metaphysis of the tibia and fill the dead space if present. PMID- 24211052 TI - Aspirin resistant patients with recent ischemic stroke. AB - Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). PMID- 24211053 TI - A simple method minimizes chylothorax after minimally invasive esophagectomy. AB - BACKGROUND: Postoperative chylothorax is a rare, but potentially fatal complication after esophagectomy. Preventive measures aimed at decreasing the incidence of chyle leakage after minimally invasive esophagectomy (MIE) could potentially reduce the high postoperative mortality associated with this complication. However, previous techniques are traumatic and time consuming. We present a simple method in the prophylaxis of chylothorax after MIE. STUDY DESIGN: A total of 344 consecutive esophageal cancer patients who underwent 3 stage MIE between June 2006 and July 2012 were included. Of these, 178 patients were given preoperative milk orally 6 hours before surgery (Group M+), and 166 underwent MIE without preoperative milk and served as controls (Group M-). Patient demographics were retrospectively collected. The incidences of intraoperative thoracic duct identification and postoperative chylothorax were recorded and statistically compared between the 2 groups. RESULTS: In this cohort, the 2 groups were comparable in clinical features including age, sex, tumor location, histologic type, and TNM stage. No patient was converted to open thoracotomy. During the thoracoscopic stage, a higher incidence of duct identification (95.5% vs 12.7%, p < 0.001) and a lower incidence of duct ligation (6.74% vs 13.25%, p = 0.039) were recorded in Group M+. Postoperatively, a total of 10 cases of chylothorax (2.91%) were observed. The incidence of chylothorax was significantly lower in Group M+ than in Group M- (0.56% vs 5.42%, p = 0.018). CONCLUSIONS: Preoperative oral administration of milk facilitates visualization of the thoracic duct and minimizes the risk of iatrogenic injury to the thoracic duct during thoracoscopic esophagectomy. It is a simple and safe method for preventing chyle leakage after MIE. A randomized and controlled trial is required to confirm these findings. PMID- 24211055 TI - Surgical simulation in 2013: why is it still not the standard in surgical training? PMID- 24211056 TI - Impact of medical malpractice environment on surgical quality and outcomes. PMID- 24211057 TI - Total joint arthroplasty and preoperative low back pain. AB - Lower extremity osteoarthritis with concomitant low-back pain (LBP) may obscure a clinician's ability to properly evaluate the status of hip or knee osteoarthritis and subsequent total joint arthroplasty (TJA) candidacy. A prospective cohort study was conducted to determine prevalence and severity of preoperative LBP among TJA patients, and the effect of TJA on alleviating LBP. Preoperative moderate to worst imaginable LBP pain on the Oswestry Disability Index (ODI) was significantly higher among hips compared to knees (28.8% vs. 16.1%, P < 0.0001). Compared to knees, hips also saw significant ODI improvement from preoperative to one-year postoperative. TJA candidates with considerable preoperative LBP should be counselled that TJA outcome may be impaired by the coexistence of spine disease, and that residual spine pain may continue following otherwise successful TJA. PMID- 24211054 TI - Effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection: a single institution experience of 1,061 consecutive patients. AB - BACKGROUND: Chronic kidney disease (CKD) is known to adversely affect cardiac and vascular surgery outcomes. We examined the effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection. STUDY DESIGN: All patients who underwent pancreatic resection between January 2005 and July 2012 were identified. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease formula. Severe CKD (stages 4-5) was defined as eGFR < 30 mL/min/1.73 m(2). Renal function also was analyzed using serum creatinine (sCr) dichotomized at 1.8 mg/dL. Primary outcomes were any complication, major complications, and respiratory failure. Multivariate models for each endpoint were constructed by including all variables with p value <= 0.10 on univariate analysis. RESULTS: There were 1,061 patients identified; 709 underwent pancreaticoduodenectomy, 307 distal pancreatectomy, and 45 central or total pancreatectomy. Median sCr value was 0.86 mg/dL (range 0.30 to 14.1 mg/dL). Eighteen patients (1.7%) had severe CKD and 31 (2.9%) had sCr >= 1.8 mg/dL. Complications occurred in 622 patients (58.6%), major complications in 198 (18.7%), and respiratory failure in 48 (4.5%). Both severe CKD and sCr >= 1.8 mg/dL were associated with any complication, major complications, and respiratory failure on univariate analysis. On multivariate analysis, severe CKD was associated with increased complications (odds ratio [OR] 5.5; 95% CI 1.3 to 25.5; p = 0.02) and respiratory failure (OR 6.1; 95% CI 1.8 to 20.5; p = 0.03), but not major complications. Using sCr >= 1.8 mg/dL as a surrogate marker for renal insufficiency, patients with sCr >= 1.8 mg/dL had increased risk of any complication (OR 3.5; 95% CI 1.3 to 9.3; p = 0.01), major complications (OR 2.2; 95% CI 1.04 to 4.8; p = 0.04), and respiratory failure (OR 4.7; 95% CI 1.8 to 12.6; p = 0.002). CONCLUSIONS: Few patients with significant renal insufficiency are candidates for pancreatic resection. Severe CKD (stages 4-5) is associated with increased risk of complication and respiratory failure. Serum creatinine >= 1.8 mg/dL may serve as a useful marker of renal insufficiency and identifies patients at significantly increased risk of any complication, major complication, and respiratory failure after pancreatic resection. PMID- 24211058 TI - Concomitant therapy in people with epilepsy: potential drug-drug interactions and patient awareness. AB - People with epilepsy (PWE) may use prescription and over-the-counter (OTC) drugs for the treatment of concomitant diseases. Combinations of these drugs, as well as dietary supplements, with antiepileptic drugs (AEDs) may lead to reduced control of seizures and of coexisting medical conditions and increased risk of adverse drug reactions (ADRs). The aims of this study were to obtain comprehensive lists of medications, dietary supplements, botanicals, and specific food components used by adult PWE and to evaluate the potential for interactions involving AEDs and patients' awareness of such potential interactions. We conducted a prospective, questionnaire-based study of PWE attending the Hadassah Hebrew University Epilepsy Clinic over a period of 7months. The questionnaire interview included the listing of medications, medicinal herbs, dietary supplements, and specific food components consumed and the knowledge of potential drug-drug interactions (DDIs), and it was conducted by a pharmacist. Drug-drug interactions were analyzed via the Micromedex online database. Out of 179 patients who attended the clinic over the study period, we interviewed 73 PWE, of which 71 were included in our final analysis. The mean number of AEDs consumed per subject was 1.7 (SD: 0.8, range: 1-4). Forty (56%) subjects were also treated with other prescription and/or OTC medications, and thirty-four (48%) took dietary supplements. Drug families most prone to DDIs involving AEDs included antipsychotic agents, selective serotonin reuptake inhibitors, and statins. Two thirds of study participants (67%) knew that DDIs may lead to ADRs, but only half (56%) were aware of the potential for reduced seizure control. Only 44% always reported treatment with AEDs to medical professionals. This study provides for the first time a comprehensive picture of prescription and OTC drugs and food supplements used by PWE. Despite a considerable potential for DDIs involving AEDs, patient awareness is limited, highlighting the importance of patient and caregiver education. PMID- 24211060 TI - CYP2D6 phenotypes and Parkinson's disease risk: a meta-analysis. AB - BACKGROUND: CYP2D6 polymorphisms have been reported to be associated with Parkinson's disease (PD) susceptibility, but the results of these previous studies were inconsistent. OBJECTIVES: To explore whether PD patients with CYP2D6 gene variation have different risk to PD to those with normal function of CYP2D6. METHODS: Systematic review with meta-analysis of case-controlled studies on the association between CYP2D6 and PD risk was conducted. Studies published up to August 1, 2013 were identified by searching electronic databases PubMed and Embase. Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) were used to estimated the association between CYP2D6 polymorphisms and PD risk in different phenotype models. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed. RESULTS: A total of 3521 PD Patients and 4476 controls from 29 case-control studies were identified. Overall, a borderline significant influence of the CYP2D6 polymorphisms on PD risk was observed (OR: 1.07, 95%CI: 0.99-1.16, p=0.106). Significant association was found when comparisons were performed in different phenotypes in PM versus EM (OR=1.33, 95% CI=1.01-1.74, p=0.044) and PM versus IM+EM (OR=1.32, 95% CI=1.11-1.56, p=0.002). In subgroup analysis stratified by country, significant association was demonstrated in British but not in other white subjects. No significant association was detected in subgroup analysis according to the age of onset and the source of patients. CONCLUSION: The present meta-analysis demonstrated that the poor metabolizer phenotype of CYP2D6 confers a significant genetic susceptibility to PD in Caucasians, especially in British white subjects. PMID- 24211059 TI - Effect of cilostazol in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. AB - Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR=0.47; 95% CI, 0.31-0.72; p<0.001), severe vasospasm (RR=0.48; 95% CI, 0.28 0.82; p=0.007), vasospasm-related new cerebral infarctions (RR=0.38; 95% CI, 0.22 0.67; p=0.001), and poor outcome (RR=0.57; 95% CI, 0.37-0.88; p=0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH. PMID- 24211061 TI - Central nervous system vasculitis associated with hepatitis C virus infection: a brain MRI-supported diagnosis. AB - BACKGROUND: The Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, being the Central Nervous System (CNS) rarely involved. CASE REPORT: We report a case of a 54 year-old black man with arterial hypertension who presented with progressively worsening headaches, apathy, somnolence and left hemiparesis. Brain MRI showed an acute ischemic lesion in the left anterior cerebral artery (ACA) and an old ischemic infarct in the right ACA territory. Brain MRI with gadolinium revealed mural thickening and contrast enhancement of the A1 and A2 segments of the ACAs, of the middle and distal basilar artery and of the P1 segment of the left posterior cerebral artery, suggesting active vasculitis. Digital angiography confirmed those irregularities and stenosis. Laboratory evaluation revealed ESR (73 mm/h), transaminase elevation, elevated HCV viral load genotype 2, positive IGRA, negative cryoglobulins, CSF protein elevation with oligoclonal bands (mirror pattern) and no pleocytosis; investigation excluded other infectious causes. Pegylated interferon alpha-2a and ribavirin, corticotherapy and tuberculosis prophylaxis were started with clinical and imagiological improvement. CONCLUSION: The typical inflammation signs of the vascular wall demonstrated by the gadolinium-enhanced MRI strengthened the hypothesis of CNS vasculitis. The association with HCV infection is rare but should be investigated once specific therapeutic is required. PMID- 24211062 TI - Chronic migraine does not increase posterior circulation territory (PCT) infarct like lesions. AB - Two population-based studies have found an increased prevalence of posterior circulation territory (PCT) infarct-like lesions in migraine, which seemed to increase with attack frequency. OBJECTIVE: To determine whether chronic migraine (CM) patients are at increased risk of PCT infarct-like lesions. METHODS: We prospectively obtained brain MRIs from adult women fulfilling CM criteria. To keep radiologists blinded we also obtained brain MRIs in 15 episodic migraine (EM) patients. MRIs were acquired on a 1.5 T unit. Protocol included whole brain weighted images in sagittal T1 (5 mm slices), axial FLAIR T2 (3 mm) and combined proton density and T2 fast spin echo (3 mm). Two independent neuroradiologists carefully analyzed all the images. RESULTS: One hundred women with CM participated. Their ages ranged from 18 to 68 years (mean 43.7) and the length of CM ranged from 0.5 to 38 years (mean 9.8). Sixty-three patients (63%) had at least one vascular risk factor. Thirty-three met analgesic overuse criteria. Fifty-one had a history of migraine with aura attacks, though aura frequency was below one per month in all patients except one. Eleven were not on preventatives. We found PCT infarct-like lesions in only 6 CM patients aged 42-64 years (mean age 54 years) who had at least two vascular risk factors. CONCLUSIONS: As frequency of PCT infarct-like lesions in our CM patients was in the low range than that found for EM in general population studies, we conclude that frequency of migraine attacks itself is not a factor increasing PCT infarct-like lesion risk. PMID- 24211063 TI - Relationships between ophthalmic artery flow direction and cognitive performance in patients with unilateral carotid artery stenosis. AB - BACKGROUND: Cerebral hypoperfusion is responsible for cognitive impairment in patients with severe carotid artery stenosis (CAS). The manifestation of reversed ophthalmic artery flow (ROAF) is not uncommon in patients with CAS, suggesting a state of intensified cerebral hypoperfusion. This study aimed to examine whether the presence of ROAF can exacerbate cognitive impairment in patients with severe unilateral CAS. METHODS: One-hundred-and-two patients with CAS and 37 age-matched volunteers participated in this case-control study. Depending on the side of CAS and occurrences of ROAF, the patients were allocated to four groups: left CAS groups with ROAF (n=28) or without ROAF (n=22), and right CAS groups with ROAF (n=26) or without ROAF (n=26). All subjects underwent a battery of neuropsychological tests. RESULTS: All patients performed worse than the control group on most tests. No significant differences were observed between patient groups (ps>0.05), except for inferior performance on psychomotor speed and visuospatial tests in the right ROAF group (ps<0.03). Hierarchical regression analyses indicated strong contributions of estimated premorbid intelligence to performance on most tests (ps<0.05). The severity of left and right CAS was distinctively associated with different functions. To a lesser extent, the severity of infarcts was also associated with impairment of psychomotor speed and some executive functions (ps<0.05). The contributions of ROAF to performance on most tests were negligible. CONCLUSION: Patients with unilateral CAS may present with specific cognitive impairment relevant to the ipsilateral hemispheric functions. However, the manifestation of ROAF does not necessarily imply more extensive or severe cognitive impairment. PMID- 24211064 TI - High risks of all-cause and cardiovascular deaths in apparently healthy middle aged people with preserved glomerular filtration rate and albuminuria: A prospective cohort study. AB - BACKGROUND: The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated. METHODS: A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45-119 ml/min/1.73 m(2)) were enrolled and divided into six groups (group 1, eGFR: 90-119 without albuminuria; group 2, eGFR: 90-119 with albuminuria; group 3, eGFR: 60-89 without albuminuria (reference); group 4, eGFR: 60-89 with albuminuria; group 5, eGFR: 45-59 without albuminuria; group 6, eGFR: 45-59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin creatinine ratio >= 30 mg/g). Outcomes included all-cause death (ACD), cardiovascular death (CVD) and neoplasm-related death (NPD). Multivariable adjusted mortality rate ratios (RR) and their 95% confidence intervals (CIs) in the groups were estimated by Poisson's regression analysis. RESULTS: The highest risk of ACD (RR (95% CIs): 3.95 (2.08-7.52)), CVD (7.15 (2.25-22.7)) and NPB (3.25 (1.26-8.38)) was observed in group 2. Subjects in group 2 were relatively young and had the highest levels of body mass index, blood pressure and HbA1c and the highest prevalence of diabetes and metabolic syndrome. CONCLUSION: Coexistence of preserved eGFR and albuminuria increases risks for ACD, CVD and NPD. Relatively young metabolic persons having both preserved eGFR and albuminuria should be considered as a very high-risk population. PMID- 24211065 TI - Proximal coronary artery intervention: stent thrombosis, restenosis and death. AB - BACKGROUND: Percutaneous coronary intervention (PCI) of lesions in the proximal left anterior descending coronary artery (LAD) may confer a worse prognosis compared with the proximal right coronary artery (RCA) and left circumflex coronary artery (LCX). METHODS: From May 2005, to May 2011 we identified all PCIs for proximal, one-vessel coronary artery disease in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We evaluated restenosis, stent thrombosis (ST) and mortality in the LAD as compared to the RCA and LCX according to stent type, bare metal (BMS) or drug-eluting stents (DES). RESULTS: 7840 single vessel proximal PCI procedures were identified. Mean follow-up time was 792 days. No differences in restenosis or ST were seen between the LAD and the RCA. The frequency of restenosis and ST was higher in the proximal LAD compared to the proximal LCX (restenosis: hazard ratio (HR) 2.28, confidence interval (CI) 1.56-3.34 p<0.001; ST: HR 2.32, CI 1.11-4.85 p=0.024). We found no difference in mortality related to coronary artery. In the proximal LAD, DES implantation was associated with a lower restenosis rate (HR 0.39, CI 0.27-0.55 p<0.001) and mortality (HR 0.58, CI 0.41-0.82 p=0.002) compared with BMS. In the proximal RCA and LCX, DES use was not associated with lower frequency of clinical restenosis or mortality. CONCLUSIONS: Following proximal coronary artery intervention restenosis was more frequent in the LAD than in the LCX. Solely in the proximal LAD we found DES use to be associated with a lower risk of restenosis and death weighted against BMS. PMID- 24211066 TI - Autotransplantation of mesenchymal stromal cells from bone-marrow to heart in patients with severe stable coronary artery disease and refractory angina--final 3-year follow-up. AB - BACKGROUND: The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (BMMSCs) in patients with severe stable coronary artery disease (CAD) and refractory angina. METHODS: Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous BMMSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. BMMSCs were injected into an ischemic, viable region of the myocardium. Patients were followed for 3 years. RESULTS: We found significant clinical improvements in exercise time (p=0.0016), angina class (CCS) (p<0.0001), weekly number of angina attacks (p<0.0001) and use of nitroglycerine from (p=0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p<0.0001). When comparing all hospital admissions from 3 years before to 3 years after treatment, we observed highly reduced admission rates for stable angina (p<0.0001), revascularization (p=0.003) and overall cardiovascular disease (p<0.0001). No early or late side effects of the treatment were observed. CONCLUSIONS: The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs, in patients with severe CAD and refractory angina, demonstrated sustained clinical effects, reduced hospital admissions for cardiovascular disease and excellent long-term safety. The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression. PMID- 24211068 TI - [Scales to evaluate pain in elderly patients suffering from dementia. Help-tools for the physiotherapist, doctor, nurse and occupational therapist]. AB - The purpose of this study was to determine which scales are being used to evaluate pain in old people suffering from dementia. A search strategy was developed to retrieve all articles (randomized controlled trials and clinical trials without randomization) published in MEDLINE, Cochrane Library Plus, PEDro and Dialnet and BMC Geriatrics from January 2000 to January 2012. Exclusion criteria were articles that did not use scales for evaluating pain in elderly patients suffering from dementia, and other type of articles (case studies, reviews...). Finally, 13 studies were included in this review. From the results obtained it appears that more studies are needed to confirm the pain scales used for the elderly suffering from dementia. Observational scales may be useful to evaluate pain in these patients. PMID- 24211067 TI - Do our children lose vagus activity? Potential time trends of children's autonomic nervous system activity. PMID- 24211069 TI - Gene expression patterns in wheat coleorhiza under cold- and biological stratification. AB - This study assessed germination of wheat seeds under cold and biological stratification and determined the expression level of gibberellins (GA) and abscisic acid (ABA) genes in coleorhiza. Both cold and biological stratification significantly (P<0.05) enhanced the rate and efficacy of germination. The spatial distance between the fungal endophyte and the seed can be a determining factor of biological stratification as seeds in direct contact with fungal endophyte showed the highest rate and efficacy of germination. Consistently high expression of GA3ox2 gene was found in wheat coleorhiza throughout the tested period of germination. The expression of ABA biosynthesis gene, TaNCED, was substantially higher in cold stratification seeds, reflecting the role of abscisic acid in stress-adaptation. Overall, this study provides molecular evidence of the importance of coleorhiza in germinating wheat seeds, in addition to reporting that the spatial distance between symbiotic partners may be a critical factor driving mycovitality. PMID- 24211070 TI - Influence of population versus convenience sampling on sample characteristics in studies of cognitive aging. AB - PURPOSE: We examined whether differences in findings of studies examining mild cognitive impairment (MCI) were associated with recruitment methods by comparing sample characteristics in two contemporaneous Australian studies, using population-based and convenience sampling. METHOD: The Sydney Memory and Aging Study invited participants randomly from the electoral roll in defined geographic areas in Sydney. The Australian Imaging, Biomarkers and Lifestyle Study of Ageing recruited cognitively normal (CN) individuals via media appeals and MCI participants via referrals from clinicians in Melbourne and Perth. Demographic and cognitive variables were harmonized, and similar diagnostic criteria were applied to both samples retrospectively. RESULTS: CN participants recruited via convenience sampling were younger, better educated, more likely to be married and have a family history of dementia, and performed better cognitively than those recruited via population-based sampling. MCI participants recruited via population-based sampling had better memory performance and were less likely to carry the apolipoprotein E epsilon4 allele than clinically referred participants but did not differ on other demographic variables. CONCLUSION: A convenience sample of normal controls is likely to be younger and better functioning and that of an MCI group likely to perform worse than a purportedly random sample. Sampling bias should be considered when interpreting findings. PMID- 24211071 TI - Reference values for respiratory events in overnight polygraphy from infants aged 1 and 3months. AB - OBJECTIVE: We aimed to determine reference values for respiratory indices in polygraphies (PGs) performed in infants aged 1 and 3months. METHODS: Healthy full term neonates were recruited on the maternity ward. They were followed up by overnight PG at the age of 1month and again at the age of 3months. Indices of respiratory events, such as apneas, hypopneas, and percentage of periodic breathing were determined in each PG. Interpretation of PGs was performed blinded to the subject's data and the time of measurement. PG indices at 1 and 3months of age were compared. RESULTS: PG recordings were obtained for 37 healthy infants (22 boys). At the age of 1month, the median (minimum-maximum) central, obstructive, and mixed apnea index was 5.5 (0.9-44.3), 0.8 (0.1-6.7), and 0.3 (0 1.2), respectively. The same figures at the age of 3months were 4.1 (1.2-27.3), 0.8 (0-2.3), and 0.1 (0-0.8), respectively. Mixed obstructive apnea-hypopnea index (MOAHI) was 1.5 (0.2-7.0) and 0.9 (0.2-4.4) at the first and second measurements, respectively (P=.017). Only 1.2% of central apneas lasted longer than 20s. Periodic breathing was present in more than 90% of subjects studied. CONCLUSIONS: The infants in our study aged ?3months had respiratory event indices that were different from older children or adults. MOAHI showed a significant decrease during the first 3months after birth. We recommend that scoring of PG in infants of 3months or younger should consider age-specific reference values. PMID- 24211072 TI - Nonapnea sleep disorders are associated with subsequent ischemic stroke risk: a nationwide, population-based, retrospective cohort study. AB - BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is related to an increased risk for stroke and cardiovascular disease. However, studies investigating the relationship between nonapnea sleep disorders (NSD) and the risk for subsequent ischemic stroke are scant. The objective of our study was to assess the association between NSD and the risk for acute ischemic stroke among patients in Taiwan. METHODS: We conducted our longitudinal nationwide, population based, retrospective study using Taiwan's National Health Insurance Research Database (NHIRD) from January 1997 to December 2001. All study participants were followed until the incidence of ischemic stroke, or until censoring due to death; until withdrawal from the insurance program; or until they were lost to follow-up by the end of 2010. Cox proportional hazard regression analysis was used to assess the association between NSD and subsequent ischemic stroke risk. RESULTS: We analyzed the data collected from 94,160 participants as a comparison cohort and 47,080 participants as a NSD cohort with the diagnosis date as the index date. The age range of cohorts was 20.0-101.7years and 64% were women. The average follow-up duration was 9.61years for the NSD cohort and 9.42years for the reference cohort. Overall, the ischemic stroke incidence was 1.48-fold higher in the NSD cohort than in the reference cohort (8.87 vs 6.00/1000 individual-years), with an adjusted hazard ratio (HR) of 1.19 after controlling for age, sex, and comorbidities. Our study also showed a 1.35-fold significantly higher risk for developing ischemic stroke in men compared to women. The adjusted HR was 31.2 for elderly patients compared with participants aged ?35years. CONCLUSIONS: Our nationwide, population-based, retrospective cohort study provides evidence that patients with NSD were at increased risk for developing ischemic stroke compared to patients without diagnosed sleep disorder, with men and the elderly being at greatest risk. PMID- 24211073 TI - Determination of anti-Mullerian hormone at estrus during a synchronized and a natural bovine estrous cycle. AB - Anti-Mullerian hormone (AMH) has been correlated with phenotypic indicators of fertility. However, the effects of exogenous hormones used during estrus synchronization on AMH have not been evaluated. Therefore, the objective of this experiment was to determine whether concentrations of AMH at estrus are similar between a synchronized compared with a natural estrous cycle. Nulliparous dairy and beef heifers (n = 68) were synchronized with the Select Synch + controlled internal drug release (CIDR) protocol (GnRH + CIDR-7 d-CIDR removal + PG). Heifers were observed for expression of estrus every 6 h until 84 h after the injection of PG. Visual detection of the subsequent estrus, considered natural estrus, occurred every 6 h from day 16 to 24 after synchronized estrus. At the time of standing estrus, ovarian structures in heifers were evaluated by transrectal ultrasonography. Blood samples were collected at estrus for analysis of concentrations of AMH during the synchronized and natural estrous cycles. The GLM and CORR procedures of SAS were used to analyze data. Concentrations of AMH between natural and synchronized estrus were positively correlated (r = 0.67; P < 0.001). Mean concentration of AMH did not differ (P > 0.05) between the natural (0.0543 +/- 0.0076 ng/mL) or synchronized (0.0428 +/- 0.0076 ng/mL) estrous cycles. In conclusion, concentrations of AMH were similar between natural and synchronized estrous cycles. Concentrations of AMH in natural and synchronized estrous cycles were highly correlated within individual heifers and varied among heifers with beef heifers having increased (P < 0.05) concentrations of AMH compared with dairy heifers (0.0638 +/- 0.01 and 0.0402 +/- 0.01 ng/mL, respectively). PMID- 24211074 TI - Particle retention in suspension-feeding fish after removal of filtration structures. AB - The suspension-feeding cichlids Oreochromis aureus (blue tilapia) and Oreochromis esculentus (ngege tilapia) are able to selectively retain small food particles. The gill rakers and microbranchiospines of these species have been assumed to function as filters. However, surgical removal of these oral structures, which also removed associated mucus, did not significantly affect the total number of 11-200 MUm particles ingested by the fish. This result supports the hypothesis that the branchial arch surfaces themselves play an important role in crossflow filtration. Both species selectively retained microspheres greater than 50 MUm with gill rakers and microbranchiospines intact as well as removed, demonstrating that neither these structures nor mucus are necessary for size selectivity to occur during biological crossflow filtration. After removal of the gill rakers and microbranchiospines, O. esculentus retained significantly more microspheres 51-70 MUm in diameter and fewer 91-130 MUm microspheres compared to retention with intact structures, but the particle size selectivity of O. aureus was not affected significantly. These results support conclusions from previous computational fluid dynamics simulations indicating that particle size can have marked effects on particle trajectory and retention inside the fish oropharyngeal cavity during crossflow filtration. The substantial inter-individual variability in particle retention by suspension-feeding fish is an unexplored area of research with the potential to increase our understanding of the factors influencing particle retention during biological filtration. PMID- 24211075 TI - A cationic cholesterol based nanocarrier for the delivery of p53-EGFP-C3 plasmid to cancer cells. AB - The p53 protein mediated anti-tumor strategy is limited due to the lack of suitable delivery agent with insignificant immunogenic response, serum compatibility, and early and easy detection of the transfected cell population. To overcome these problems, we generated a p53-EGFP-C3 fusion construct which expressed easily detectable green fluorescence protein (GFP) and allowed an estimation of p53 mediated anti-tumor activity. A mixture of cationic cholesterol gemini (Chol-5L) with natural lipid, DOPE (molar ratio 1:4), acronymed as Chol 5LD, formed a nano-liposome as characterized by various physical methods. The prepared clone was evaluated for the expression of GFP and functional p53 in HeLa and two additional cell lines with varied p53 status namely, H1299 (p53(-/-)) and HEK293T (p53(+/+)). Transfected cells were screened using RT-PCR, Western blotting, FACS analysis, MTT, Trypan blue assay and visualized under a fluorescence microscope. The p53-EGFP-C3 fusion protein induced apoptosis in cancer cells as evident from DNA fragmentation, cell cycle analysis, Annexin-V staining and PARP cleavage assays. The transfection and apoptosis induction efficiency of Chol-5LD was significantly higher than commercial reagents Lipofectamine2000 and Effectene irrespective of the cell lines examined. Further it significantly decreases the xenograft tumor volume in nude mice tumors via apoptosis as observed in H&E staining. PMID- 24211076 TI - Controlling stem cell-mediated bone regeneration through tailored mechanical properties of collagen scaffolds. AB - Mechanical properties of the extracellular matrix (ECM) play an essential role in cell fate determination. To study the role of mechanical properties of ECM in stem cell-mediated bone regeneration, we used a 3D in vivo ossicle model that recapitulates endochondral bone formation. Three-dimensional gelatin scaffolds with distinct stiffness were developed using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) mediated zero-length crosslinking. The mechanical strength of the scaffolds was significantly increased by EDC treatment, while the microstructure of the scaffold was preserved. Cell behavior on the scaffolds with different mechanical properties was evaluated in vitro and in vivo. EDC-treated scaffolds promoted early chondrogenic differentiation, while it promoted both chondrogenic and osteogenic differentiation at later time points. Both micro-computed tomography and histologic data demonstrated that EDC treatment significantly increased trabecular bone formation by transplanted cells transduced with AdBMP. Moreover, significantly increased chondrogenesis was observed in the EDC-treated scaffolds. Based on both in vitro and in vivo data, we conclude that the high mechanical strength of 3D scaffolds promoted stem cell mediated bone regeneration by promoting endochondral ossification. These data suggest a new method for harnessing stem cells for bone regeneration in vivo by tailoring the mechanical properties of 3D scaffolds. PMID- 24211077 TI - A review of polypeptide-based polymersomes. AB - Self-assembled systems from biodegradable amphiphilic polymers at the nanometer scale, such as nanotubes, nanoparticles, polymer micelles, nanogels, and polymersomes, have attracted much attention especially in biomedical fields. Among these nano-aggregates, polymersomes have attracted tremendous interests as versatile carriers due to their colloidal stability, tunable membrane properties and ability of encapsulating or integrating a broad range of drugs and molecules. Biodegradable block polymers, especially aliphatic polyesters such as polylactide, polyglycolide and poly (epsilon-caprolactone) have been widely used as biomedical materials for a long time to well fit the requirement of biomedical drug carriers. To have a precise control of the aggregation behavior of nano aggregates, the more ordered polypeptide has been used to self-assemble into the drug carriers. In this review we focus on the study of polymersomes which also named pepsomes formed by polypeptide-based copolymers and attempt to clarify the polypeptide-based polymersomes from following aspects: synthesis and characterization of the polypeptide-based copolymers, preparation, multifunction and application of polypeptide-based polymersomes. PMID- 24211078 TI - A systems toxicology approach to the surface functionality control of graphene cell interactions. AB - The raised considerable concerns about the possible environmental health and safety impacts of graphene nanomaterials and their derivatives originated from their potential widespread applications. We performed a comprehensive study about biological interaction of grapheme nanomaterials, specifically in regard to its differential surface functionalization (oxidation status), by using OMICS in graphene oxide (GO) and reduced graphene oxide (rGO) treated HepG2 cells. Differential surface chemistry (particularly, oxidation - O/C ratio) modulates hydrophobicity/philicity of GO/rGO which in turn governs their biological interaction potentiality. Similar toxic responses (cytotoxicity, DNA damage, oxidative stress) with differential dose dependency were observed for both GO and rGO but they exhibited distinct mechanism, such as, hydrophilic GO showed cellular uptake, NADPH oxidase dependent ROS formation, high deregulation of antioxidant/DNA repair/apoptosis related genes, conversely, hydrophobic rGO was found to mostly adsorbed at cell surface without internalization, ROS generation by physical interaction, poor gene regulation etc. Global gene expression and pathway analysis displayed that TGFbeta1 mediated signaling played the central role in GO induced biological/toxicological effect whereas rGO might elicited host-pathogen (viral) interaction and innate immune response through TLR4-NFkB pathway. In brief, the distinct biological and molecular mechanisms of GO/rGO were attributed to their differential surface oxidation status. PMID- 24211079 TI - Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma. AB - Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7 micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma targeting potential of CREKA-micelles and provide the foundation for CREKA mediated, targeted therapy of glioma. PMID- 24211081 TI - Effect of stereochemistry, chain length and sequence pattern on antimicrobial properties of short synthetic beta-sheet forming peptide amphiphiles. AB - In the face of mounting global antibiotics resistance, the identification and development of membrane-active antimicrobial peptides (AMPs) as an alternative class of antimicrobial agent have gained significant attention. The physical perturbation and disruption of microbial membranes by the AMPs have been proposed to be an effective means to overcome conventional mechanisms of drug resistance. Recently, we have reported the design of a series of short synthetic beta-sheet folding peptide amphiphiles comprised of recurring (X1Y1X2Y2)n-NH2 sequences where X: hydrophobic amino acids, Y: cationic amino acids and n: number of repeat units. In efforts to investigate the effects of key parameters including stereochemistry, chain length and sequence pattern on antimicrobial effects, systematic d-amino acid substitutions of the lead peptides (IRIK)2-NH2 (IK8-all L) and (IRVK)3-NH2 (IK12-all L) were performed. It was found that the corresponding D-enantiomers exhibited stronger antimicrobial activities with minimal or no change in hemolytic activities, hence translating very high selectivity indices of 407.0 and >>9.8 for IK8-all D and IK12-all D respectively. IK8-all D was also demonstrated to be stable to degradation by broad spectrum proteases trypsin and proteinase K. The membrane disrupting bactericidal properties of IK8-all D effectively prevented drug resistance development and inhibited the growth of various clinically isolated MRSA, VRE, Acinetobacter baumanni, Pseudomonas aeruginosa, Cryptococcus. neoformans and Mycobacterium tuberculosis. Significant reduction in intracellular bacteria counts was also observed following treatment with IK8-all D in the Staphylococcus. aureus infected mouse macrophage cell line RAW264.7 (P < 0.01). These results suggest that the d-amino acids substituted beta-sheet forming peptide IK8-all D with its enhanced antimicrobial activities and improved protease stability, is a promising therapeutic candidate with potential to combat antibiotics resistance in various clinical applications. PMID- 24211080 TI - Maximizing gene delivery efficiencies of cationic helical polypeptides via balanced membrane penetration and cellular targeting. AB - The application of non-viral gene delivery vectors is often accompanied with the poor correlation between transfection efficiency and the safety profiles of vectors. Vectors with high transfection efficiencies often suffer from high toxicities, making it unlikely to improve their efficiencies by increasing the DNA dosage. In the current study, we developed a ternary complex system which consisted of a highly membrane-active cationic helical polypeptide (PVBLG-8), a low-toxic, membrane-inactive cationic helical polypeptide (PVBLG-7) capable of mediating mannose receptor targeting, and DNA. The PVBLG-7 moiety notably enhanced the cellular uptake and transfection efficiency of PVBLG-8 in a variety of mannose receptor-expressing cell types (HeLa, COS-7, and Raw 264.7), while it did not compromise the membrane permeability of PVBLG-8 or bring additional cytotoxicities. Because of the simplicity and adjustability of the self-assembly approach, optimal formulations of the ternary complexes with a proper balance between membrane activity and targeting capability were easily identified in each specific cell type. The optimal ternary complexes displayed desired cell tolerability and markedly outperformed the PVBLG-8/DNA binary complexes as well as commercial reagent LipofectamineTM 2000 in terms of transfection efficiency. This study therefore provides an effective and facile strategy to overcome the efficiency-toxicity poor correlation of non-viral vectors, which contributes insights into the design strategy of effective and safe non-viral gene delivery vectors. PMID- 24211082 TI - Copper-free azide-alkyne cycloaddition of targeting peptides to porous silicon nanoparticles for intracellular drug uptake. AB - Porous silicon (PSi) has been demonstrated as a promising drug delivery vector for poorly water-soluble drugs. Here, a simple and efficient method based on copper-free click chemistry was used to introduce targeting moieties to PSi nanoparticles in order to enhance the intracellular uptake and tumor specific targeting hydrophobic drug delivery. Two RGD derivatives (RGDS and iRGD) with azide-terminated groups were conjugated to bicyclononyne-functionalized PSi nanoparticles via copper-free azide-alkyne cycloaddition. The surface functionalization was performed in aqueous solution at 37 degrees C for 30 min resulting in conjugation efficiencies of 15.2 and 3.4% (molar ratios) and the nanoparticle size increased from 165.6 nm to 179.6 and 188.8 nm for RGDS and iRGD, respectively. The peptides modification enhanced the cell uptake efficiency of PSi nanoparticles in EA.hy926 cells. PSi-RGDS and PSi-iRGD nanoparticles loaded with sorafenib showed a similar trend for the in vitro antiproliferation activity compared to sorafenib dissolved in dimethyl sulfoxide. Furthermore, sorafenib-loaded PSi-RGDS deliver the drug intracellulary efficiently due to the higher surface conjugation ratio, resulting in enhanced in vitro antiproliferation effect. Our results highlight the surface functionalization methodology for PSi nanoparticles applied here as a universal method to introduce functional moieties onto the surface of PSi nanoparticles and demonstrate their potential active targeting properties for anticancer drug delivery. PMID- 24211083 TI - Air-bone gap in ears with a well-repaired tympanic membrane after Type III and Type IV tympanoplasty. AB - OBJECTIVE: To investigate the air-bone conduction hearing gap (A-B gap) after Type III and Type IV stapes columella tympanoplasty in ears with mobile stapes and a well repaired tympanic membrane (TM). METHODS: Those patients who underwent tympanoplasty in our hospital between 2003 and 2009 and satisfied the following criteria were eligible: (1) good stapes mobility, confirmed intraoperatively; (2) postoperative TM and/or computed tomography (CT) findings that showed a well aerated tympanic cavity without TM perforation, otorrhea, or middle ear effusion; and (3) measurable air and bone conduction hearing thresholds 1 year postoperatively at all test frequencies (250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz). RESULTS: Hearing results were better after Type III tympanoplasty than after Type IV tympanoplasty. After Type III (n=70) and Type IV (n=24) tympanoplasty, the respective mean A-B gaps were 16.4 +/- 7.2 dB and 20.1 +/- 5.6 dB, respectively. The mean A-B gap was significantly smaller after Type III tympanoplasty than after Type IV tympanoplasty (p<0.05). Regardless of the type of tympanoplasty, the postoperative A-B gap was greatest at 4 kHz. CONCLUSION: The mean A-B gap was smaller after Type III tympanoplasty than after Type IV tympanoplasty. The magnitude of the A-B gap was greatest at 4 kHz in both procedures. PMID- 24211084 TI - Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: a critical analysis of patterns and outcomes. AB - OBJECTIVE: With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16 negative disease. METHODS: Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed. RESULTS: Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI: 8-32.5%, p=0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95% CI: 7-18%) while all p16 negative patients died within 34 months (p<0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis. CONCLUSIONS: The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival. PMID- 24211085 TI - Hyperactivity and impulsivity in children with untreated allergic rhinitis: corroborated by rating scale and continuous performance test. AB - BACKGROUND: Allergic rhinitis (AR) is the most common chronic allergic disease in school-age children. An increased prevalence of attention deficit hyperactivity disorder (ADHD) in AR patients has been reported; however, inattention and hyperactivity in AR children have not been investigated using objective and scientific measurements. METHODS: We used AR symptom score, ADHD symptom scale, and computerized continuous performance test (CPT) to study the attention and impulsivity in AR children, age-matched controls, and ADHD children (aged 6-15 years). Univariate and multivariate linear regression analyses were applied to identify risk factors for impulsivity and inattention in AR children. RESULTS: Twenty-nine controls, 10 ADHD, and 105 AR children were enrolled. There were no differences in age and sex among the three groups. The scores of Hyperactivity/Impulsivity subscales of ADHD symptoms from both parents and teachers were significantly higher in the AR children. The CPT in AR children revealed higher commission errors, shorter reaction times, and more perseveration. Risk factors for inattention and impulsivity in AR children included younger age, male sex, higher AR symptom scores, persistent AR, moderate/severe AR, multiple atopic diseases, family history of atopy, and possible comorbidity with ADHD. CONCLUSION: Care for AR children should not only involve treating their allergy, but also monitoring the possible comorbidities of impulsivity and inattention. In children with impulsivity, AR should be considered in addition to ADHD. PMID- 24211086 TI - Asthma exacerbation in children: a practical review. AB - Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important. PMID- 24211087 TI - Medical student manikins - free plastic surgery training for super models. PMID- 24211088 TI - Characterisation of SCCmec elements in methicillin-resistant Staphylococcus aureus isolated from burn patients. AB - Staphylococcus aureus is an important pathogen, especially in burn units all around the world. Because of the emergence of the beta-lactam antibiotic resistant strains since 1961, concern about the prevalence of methicillin resistant S. aureus (MRSA) has increased in these units. Resistance to methicillin is mediated by penicillin-binding proteins (PBPs) that have enough affinity for binding to the beta-lactam ring, but another kind of protein (PBP2alpha), which is encoded by the mecA gene, has a lower affinity for binding to these antibiotics. The mecA gene is transferred by SCCmec (staphylococcal cassette chromosome mec) as a mobile genetic element, exclusively found in the Staphylococcus genus. Identification of the frequency of the mecA gene, different SCCmec types and also its incidence may have benefit in surveillance prevention and control of MRSA strains in burn units. In this study, 40 S. aureus isolates were collected from patients hospitalised in Motahari burn center of Tehran, during 2012-2013. Conventional microbiological methods were applied and the confirmed isolates were stored at -20 degrees C for molecular polymerase chain reaction (PCR) tests. The antibiotic resistance pattern was performed by disc diffusion method and finally the different SCCmec types were determined by specific primers. During this research, 40 isolates of S. aureus were collected from burn patients, of which (37.5%) of the specimens belonged to female patients and 62.5% to male patients. The aetiology of the burn was classified as follows: open flame (35%), liquid (32.5%), chemical (5%) and other (27.5%). By a disc diffusion method, no resistance pattern was observed to vancomycin and fosfomycin. Based on a multiplex PCR assay, the five different SCCmec types were detected as: 47.5% type III, 25% type IV, 10% type V, 10% type II and 7.5% type I. PMID- 24211089 TI - Loads on a vertebral body replacement during locomotion measured in vivo. AB - Walking is one of the most important activities in daily life, and walking exposes the spine to a high number of loading cycles. Little is known about the spinal loads during walking. Telemeterized spinal implants can provide data about their loading during different activities. The aim of this study was to measure the loads on a vertebral body replacement (VBR) during level and staircase walking and to determine the effects of walking speed and using walking aids. Telemeterized VBRs were implanted in five patients suffering from compression fractures of the L1 or L3 lumbar vertebral body. The implant allows measurements of three force and three moment components. The resultant force on the VBR was measured during level and staircase walking, when walking on a treadmill at different speeds, and when using a wheeled invalid walker or crutches. On average, the resultant force on the VBR for level walking was 171% of the value for standing. This force value increased to 265% of the standing force when ascending stairs and to 225% when descending stairs. Walking speed had a strong effect on the implant force. Using a walker during ambulation on level ground reduced the force on the implant to 62% of standing forces, whereas using two crutches had only a minor effect. Walking causes much higher forces on the VBR than standing. A strong force reduction can be achieved by using a walker. PMID- 24211090 TI - The relative associations of beta-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: the MASALA study. AB - AIMS: We assessed the relative associations of beta-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. METHODS: A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated beta-cell function. Visceral fat was measured by abdominal CT. After 2.5years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. RESULTS: Mean age was 57+/ 8years and BMI 26.1+/-4.6kg/m(2). Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-years) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-beta (OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. CONCLUSIONS: The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-beta with incident glycemic progression implies innate beta-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia. PMID- 24211091 TI - The economic burden of progressive chronic kidney disease among patients with type 2 diabetes. AB - AIMS: To estimate the rate of progression of chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) and calculate medical costs associated with progression. METHODS: We conducted a retrospective cohort study of 25,576 members at Kaiser Permanente who had T2D and at least one serum creatinine measurement in 2005. Using estimated glomerular filtration rate (eGFR), we assigned patients to baseline stages of kidney function (stage 0-2, >60ml/min/1.73m(2), n=21,008; stage 3, 30-59, n=3,885; stage 4, 15-29, n=683). We examined all subsequent eGFRs through 2010 to assess progression of kidney disease. Medical costs at baseline and incremental costs during follow-up were assessed. RESULTS: Mean age of patients was 60.6years, 51% were men, and mean diabetes duration was 5.3years. At baseline, 17.9% of patients with T2D also had stage 3 or 4 CKD. Incremental adjusted costs that occurred over follow-up (from baseline) was on average $4569, $12,617, and $33,162 per patient per year higher among patients who progressed from baseline stage 0-2, stage 3, and stage 4 CKD, respectively, compared to those who did not progress. Across all stages of CKD, those who progressed to a higher stage of CKD from baseline had follow-up costs that ranged from 2 to 4 times higher than those who did not progress. CONCLUSIONS: Progression of CKD in T2D drives substantial medical care costs. Interventions designed to minimize decline in progressive kidney function, particularly among patients with stage 3 or 4 CKD, may reduce the economic burden of CKD in T2D. PMID- 24211092 TI - [Medical students and drug marketing]. AB - OBJECTIVE: To determine the exposure of medical students to the marketing activities of the pharmaceutical industry, and identify their opinions and attitudes, and also the possible effects this exposure on their training and future professional practice. DESIGN: Descriptive cross-sectional. SETTING: University of Zaragoza Faculty of Medicine. PARTICIPANTS: Third, fourth, fifth and sixth year medical students. METHODS: The information was obtained using a previously adapted, self-report questionnaire on the exposure, attitudes and perceived suitability of drug marketing activities. Percentages were calculated for the categorical variables, applying the chi squared test for the comparison between the groups. A logistic regression was performed to determine the factors associated with their attitudes towards these activities. RESULTS: A total of 369 questionnaires were returned (93% of those attending classes). The exposure to marketing activities is high, particularly in the clinical stage (78.6% said to have received a gift non-educational gift). The students recognised the possible biases and repercussions in professional practice, although with ambiguity and contradictions. The most accepted activities are those associated with training, and the most critical attitudes appear in the clinical stage, particularly in the sixth year. CONCLUSIONS: Exposure to drug marketing by medical students and its possible training and professional effects is frequent and significant. The training environment is particularly open to promotional activities. The differences observed in the later years suggest the need for a specific curriculum subject and development of reflective attitudes by the students themselves. PMID- 24211093 TI - Comment on "Postpartum testing rates among women with a history of gestational diabetes" by Carson et al. PMID- 24211094 TI - WT1 isoform expression pattern in acute myeloid leukemia. AB - WT1 plays a dual role in leukemia development, probably due to an imbalance in the expression of the 4 main WT1 isoforms. We quantify their expression and evaluate them in a series of AML patients. Our data showed a predominant expression of isoform D in AML, although in a lower quantity than in normal CD34+ cells. We found a positive correlation between the total WT1 expression and A, B and C isoforms. The overexpression of WT1 in AML might be due to a relative increase in A, B and C isoforms, together with a relative decrease in isoform D expression. PMID- 24211095 TI - Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway. AB - Arsenic trioxide (As2O3) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As2O3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2MUM As2O3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As2O3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As2O3 and prevented the As2O3 induced cytotoxicity of WSU-CLL cells. These results suggest that As2O3 may be of therapeutic value for chronic lymphocytic leukemia. PMID- 24211097 TI - A predictive model of complications after spine surgery: the National Surgical Quality Improvement Program (NSQIP) 2005-2010. AB - BACKGROUND CONTEXT: There is increasing scrutiny by several regulatory bodies regarding the complications of spine surgery. Precise delineation of the risks contributing to those complications remains a topic of debate. PURPOSE: We attempted to create a predictive model of complications in patients undergoing spine surgery. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: A total of 13,660 patients registered in the American College of Surgeons National Quality Improvement Project (NSQIP) database. OUTCOME MEASURES: Thirty day postoperative risks of stroke, myocardial infarction, death, infection, urinary tract infection (UTI), deep vein thrombosis (DVT), pulmonary embolism (PE), and return to the operating room. METHODS: We performed a retrospective cohort study involving patients who underwent spine surgery between 2005 and 2010 and were registered in NSQIP. A model for outcome prediction based on individual patient characteristics was developed. RESULTS: Of the 13,660 patients, 2,719 underwent anterior approaches (19.9%), 565 corpectomies (4.1%), and 1,757 fusions (12.9%). The respective 30-day postoperative risks were 0.05% for stroke, 0.2% for MI, 0.25% for death, 0.3% for infection, 1.37% for UTI, 0.6% for DVT, 0.29% for PE, and 3.15% for return to the operating room. Multivariate analysis demonstrated that increasing age, more extensive operations (fusion, corpectomy), medical deconditioning (weight loss, dialysis, peripheral vascular disease, coronary artery disease, chronic obstructive pulmonary disease, diabetes), increasing body mass index, non-independent mobilization (preoperative neurologic deficit), and bleeding disorders were independently associated with a more than 3 days' length of stay. A validated model for outcome prediction based on individual patient characteristics was developed. The accuracy of the model was estimated by the area under the receiver operating characteristic curve, which was 0.95, 0.82, 0.87, 0.75, 0.74, 0.78, 0.76, 0.74, and 0.65 for postoperative risk of stroke, myocardial infarction, death, infection, DVT, PE, UTI, length of stay of 3 days or longer, and return to the operating room, respectively. CONCLUSIONS: Our model can provide individualized estimates of the risks of postoperative complications based on preoperative conditions, and can potentially be used as an adjunct in decision-making for spine surgery. PMID- 24211096 TI - Investigating the role of DNA damage in tobacco smoking-induced spine degeneration. AB - BACKGROUND CONTEXT: Tobacco smoking is a key risk factor for spine degeneration. However, the underlying mechanism by which smoking induces degeneration is not known. Recent studies implicate DNA damage as a cause of spine and intervertebral disc degeneration. Because tobacco smoke contains many genotoxins, we hypothesized that tobacco smoking promotes spine degeneration by inducing cellular DNA damage. PURPOSE: To determine if DNA damage plays a causal role in smoking-induced spine degeneration. STUDY DESIGN: To compare the effect of chronic tobacco smoke inhalation on intervertebral disc and vertebral bone in normal and DNA repair-deficient mice to determine the contribution of DNA damage to degenerative changes. METHODS: Two-month-old wild-type (C57BL/6) and DNA repair-deficient Ercc1(-/Delta) mice were exposed to tobacco smoke by direct inhalation (4 cigarettes/day, 5 days/week for 7 weeks) to model first-hand smoking in humans. Total disc proteoglycan (PG) content (1,9-dimethylmethylene blue assay), PG synthesis ((35)S-sulfate incorporation assay), aggrecan proteolysis (immunoblotting analysis), and vertebral bone morphology (microcomputed tomography) were measured. RESULTS: Exposure of wild-type mice to tobacco smoke led to a 19% increase in vertebral porosity and a 61% decrease in trabecular bone volume. Intervertebral discs of smoke-exposed animals also showed a 2.6-fold decrease in GAG content and an 8.1-fold decrease in new PG synthesis. These smoking-induced degenerative changes were similar but not worse in Ercc1( /Delta) mice. CONCLUSIONS: Short-term exposure to high levels of primary tobacco smoke inhalation promotes degeneration of vertebral bone and discs. Disc degeneration is primarily driven by reduced synthesis of proteoglycans needed for vertebral cushioning. Degeneration was not exacerbated in congenic DNA repair deficient mice, indicating that DNA damage per se does not have a significant causal role in driving smoke-induced spine degeneration. PMID- 24211098 TI - Adult thoracolumbar and lumbar scoliosis treated with long vertebral fusion to the sacropelvis: a comparison between new hybrid selective spinal fusion versus anterior-posterior spinal instrumentation. AB - BACKGROUND CONTEXT: Combined anteroposterior spinal fusion with instrumentation has been used for many years to treat adult thoracolumbar/lumbar scoliosis. This surgery remains a technical challenge to spine surgeons, and current literature reports high complication rates. PURPOSE: The purpose of this study is to validate a new hybrid technique (a combination of single-rod anterior instrumentation and a shorter posterior instrumentation to the sacrum) to treat adult thoracolumbar/lumbar scoliosis. STUDY DESIGN: This study is a retrospective consecutive case series of surgically treated patients with adult lumbar or thoracolumbar scoliosis. PATIENT SAMPLE: This is a retrospective study of 33 matched pairs of patients with adult scoliosis who underwent two different surgical procedures: a new hybrid technique versus a third-generation anteroposterior spinal fusion. OUTCOME MEASURES: Preoperative and postoperative outcome measures include self-report measures, physiological measures, and functional measures. METHODS: In a retrospective case-control study, 33 patients treated with the hybrid technique were matched with 33 patients treated with traditional anteroposterior fusion based on preoperative radiographic parameters. Mean follow-up in the hybrid group was 5.3 years (range, 2-11 years), compared with 4.6 years (range, 2-10 years) in the control group. Operating room (OR) time, estimated blood loss, and levels fused were collected as surrogates for surgical morbidity. Radiographic parameters were collected preoperatively, postoperatively, and at final follow-up. The Scoliosis Research Society Patient Questionnaire (SRS-22r) and Oswestry Disability Index (ODI) scores were collected for clinical outcomes. RESULTS: Operating room time, EBL, and levels fused were significantly less in the hybrid group compared with the control group (p<.0001). The postoperative thoracic Cobb angle was similar between the hybrid and control techniques (p=.24); however, the hybrid technique showed significant improvement in the thoracolumbar/lumbar curves (p=.004) and the lumbosacral fractional curve (p<.0001). The major complication rate was less in the hybrid group compared with the control group (18% vs. 39%, p=.01). Clinical outcomes at final follow-up were not significantly different based on overall SRS-22r scores and ODI scores. CONCLUSION: The new hybrid technique demonstrates good long-term results, with less morbidity and fewer complications than traditional anteroposterior surgery select patients with thoracolumbar/lumbar scoliosis. This study received no funding. No potential conflict of interest-associated bias existed. PMID- 24211099 TI - Early postoperative fear of movement predicts pain, disability, and physical health six months after spinal surgery for degenerative conditions. AB - BACKGROUND CONTEXT: The fear-avoidance model offers a promising framework for understanding the development of chronic postoperative pain and disability. However, limited research has examined this model in patients undergoing spinal surgery. PURPOSE: To determine whether preoperative and early postoperative fear of movement predicts pain, disability, and physical health at 6 months following spinal surgery for degenerative conditions, after controlling for depressive symptoms and other potential confounding variables. STUDY DESIGN/SETTING: A prospective cohort study conducted at an academic outpatient clinic. PATIENT SAMPLE: One hundred forty-one patients undergoing surgery for lumbar or cervical degenerative conditions. OUTCOME MEASURES: Self-reported pain and disability were measured with the Brief Pain Inventory and the Oswestry Disability Index/Neck Disability Index, respectively. The physical composite scale of the 12-Item Short Form Health Survey (SF-12) measured physical health. METHODS: Data collection occurred preoperatively and at 6 weeks and 6 months following surgery. Fear of movement was measured with the Tampa Scale for Kinesiophobia and depression with the Prime-MD PHQ-9. RESULTS: One hundred and twenty patients (85% follow-up) completed the 6-month postoperative assessment. Multivariable mixed-method linear regression analyses found that early postoperative fear of movement (6 weeks) predicted pain intensity, pain interference, disability, and physical health at 6 month follow-up (p<.05). Preoperative and early postoperative depression predicted pain interference, disability, and physical health. CONCLUSION: Results provide support for the fear-avoidance model in a postsurgical spine population. Early postoperative screening for fear of movement and depressive symptoms that do not acutely improve following surgical intervention appears warranted. Cognitive and behavioral strategies may be beneficial for postsurgical patients with high fear of movement and/or depressive symptoms. PMID- 24211100 TI - Changes in metal contamination levels in estuarine sediments around India--an assessment. AB - This review is the first attempt to comprehend the changes in metal contamination levels in surface estuarine sediments with changing time around India. Contamination factor, geoaccumulation index, pollution load index, effects range low and effects range median analysis were used to evaluate the quality of the estuarine sediments (by using the available literature data). This study suggests that estuarine sediments from the east coast of India were comparatively less contaminated by metals than the west coast. Sediments from those estuaries were found to be more contaminated by metals on which major cities are located. An improvement in estuarine sediment quality (in terms of metal contamination) over time around India was noticed. This study provides managers and decision-makers of environmental protection agency with a better scientific understanding for decision-making in controlling metal pollution in estuarine sediments around India. PMID- 24211101 TI - Impact of environmental pollution on caged mussels Mytilus galloprovincialis using NMR-based metabolomics. AB - Metabolic responses to environmental pollution, mainly related to Hg and PAHs, were investigated in mussels. Specimens of Mytilus galloprovincialis, sedentary filter-feeders, were caged in anthropogenic-impacted and reference sites along the Augusta coastline (Sicily, Italy). The gills, mainly involved in nutrient uptake, digestion and gas exchange, were selected as target organ being the first organ to be affected by pollutants. Severe alterations in gill tissue were observed in mussels from the industrial area compared with control, while gill metabolic profiles, obtained by (1)H NMR spectroscopy and analyzed by multivariate statistics, exhibited significant changes in amino acids, energy metabolites, osmolytes and neurotransmitters. Overall, the morphological changes and metabolic disturbance detected in gill tissues may suggest that the mussels transplanted to the contaminated field site were suffering from adverse environmental condition. The concurrent morphological and metabolomic investigations as applied here result effective in assessing the environmental influences on health status of aquatic organisms. PMID- 24211102 TI - Neurovascular quantitative study of the uterosacral ligament related to nerve sparing radical hysterectomy. AB - OBJECTIVE: To analyze the distribution of autonomic nerves and blood and lymphatic vessels in the uterosacral ligament, elucidate detailed anatomy at a surgical level and provide pathobiological evidence for improvement of nerve sparing radical hysterectomy. STUDY DESIGN: Surgical samples were collected from 15 patients who underwent radical hysterectomy for early stage cervical cancer (FIGO Ib1-IIa). Twenty-nine fresh specimens were divided into cervical, intermediate and sacral sections, and then subdivided into superficial and deep portions from the middle: the medial surface and lateral surface were also subdivided in order to analyze lymphatic vessels. The numbers of nerve branches in each section or portion of the section were analyzed. The lengths of the uterosacral ligaments were measured and immunohistochemistry staining was studied. Autonomic nerves, blood vessels and lymphatic vessels were quantitatively analyzed using image analysis software and biological stereology. RESULTS: The volume density of sympathetic nerves in the deep portion was significantly higher than in the superficial portion (p<0.05), and the number of nerves was greatest in the cervical section (p<0.05). The volume density of blood vessels was not significantly different between the two portions (p>0.05) or among the three sections (p>0.05), and the volume density of the lymphatic vessels was greater in the medial surface (p<0.05), with most of them in the cervical section (p<0.05). CONCLUSIONS: Our study provides systematic mapping of the location and distribution of autonomic nerve branches, blood vessels and lymphatic vessels in the uterosacral ligament. PMID- 24211103 TI - Effects of monitoring strategies on seizures in pregnant women on lamotrigine: a meta-analysis. AB - OBJECTIVES: Pregnant women with epilepsy have a significantly increased risk of mortality and morbidity compared to non-pregnant women. At least one in 250 pregnancies is exposed to anti-epileptic drugs (AED). Seizure deterioration occurs in up to a third of pregnant women. AED levels fall in most pregnant women, although it is uncertain that this is responsible for seizure deterioration rather than a hormonal effect. Current practice of AED monitoring is either therapeutic drug monitoring (TDM) or clinical features monitoring (CFM) to adjust the AED dose. We have systematically reviewed the effectiveness of the two monitoring regimens for AEDs, especially lamotrigine, the most commonly used AED in pregnancy on maternal and fetal outcomes. STUDY DESIGN: We searched MEDLINE (1966-2012), EMBASE (1980-2012) and Cochrane, for relevant citations on the effectiveness of different monitoring strategies on seizure deterioration in pregnant women with epilepsy on lamotrigine. Study selection, quality assessment and data extraction were carried out by two independent reviewers. We calculated the rates of deterioration in seizures with the two strategies and pooled the estimates with random effects meta-analysis. RESULTS: Six observational studies (n=132) evaluated the effectiveness of the two monitoring strategies on pregnant women with epilepsy on lamotrigine. There were no randomised controlled trials. The rate of seizure deterioration was 0.30 (95% CI 0.21-0.41) in women monitored by therapeutic drug monitoring (TDM) compared to 0.73 (95% CI 0.56-0.86) in those receiving clinical feature monitoring (CFM) alone. CONCLUSION: Evidence based on observational data suggests that monitoring of AED levels in pregnancy reduces seizure deterioration, although the included studies have numerous sources of bias. There is paucity of evidence to make firm recommendations on optimal monitoring of AED drugs in pregnancy. Further research is needed to advise on the best clinical practice in managing AED in pregnancy. PMID- 24211104 TI - Observed changes in first metatarsal and medial cuneiform positions after first metatarsophalangeal joint arthrodesis. AB - The first intermetatarsal angle (IMA) is known to decrease after first metatarsophalangeal joint arthrodesis, although the exact mechanism by which this decrease occurs is not known. We measured the first IMA and obliquity of the medial cuneiform on anteroposterior weightbearing preoperative and postoperative radiographs in 86 feet and analyzed the statistical correlation between the IMA and the medial cuneiform angle. A change in the first IMA after first metatarsophalangeal joint fusion showed a strong positive correlation with a change in cuneiform obliquity (p < .0001). This finding was consistent in the direction and magnitude in each of 3 clinical subgroups: normal, p = .087; moderate deformity, p = .011; and severe deformity, p = .10. A comparison of the preoperative IMA and cuneiform obliquity revealed a trend toward a positive relationship but did not reach statistical significance (p = .08). The preoperative association between the IMA and medial cuneiform obliquity was not significant in any clinical subgroup, and the postoperative association between the IMA and cuneiform obliquity was not significant (p = .65). Clinical subgroup analysis showed no significant association between the IMA and the normal (p = .73) and moderately (p = .69) deformed feet, although the postoperative association between the IMA and cuneiform obliquity in the severely deformed group was significantly (p = .034) positive. A linear relationship between the reduction of the first IMA and medial cuneiform obliquity after metatarsophalangeal joint fusion was observed. Our findings suggest that frontal plane rotation influences cuneiform obliquity. PMID- 24211105 TI - Evaluation of the benefit of emergency vaccination in a foot-and-mouth disease free country with low livestock density. AB - Foot-and-mouth disease (FMD) is highly contagious and one of the most economically devastating diseases of cloven-hoofed animals. Scientific-based preparedness about how to best control the disease in a previously FMD-free country is therefore essential for veterinary services. The present study used a spatial, stochastic epidemic simulation model to compare the effectiveness of emergency vaccination with conventional (non-vaccination) control measures in Switzerland, a low-livestock density country. Model results revealed that emergency vaccination with a radius of 3 km or 10 km around infected premises (IP) did not significantly reduce either the cumulative herd incidence or epidemic duration if started in a small epidemic situation where the number of IPs is still low. However, in a situation where the epidemic has become extensive, both the cumulative herd incidence and epidemic duration are reduced significantly if vaccination were implemented with a radius of 10 km around IPs. The effect of different levels of conventional strategy measures was also explored for the non-vaccination strategy. It was found that a lower compliance level of farmers for movement restrictions and delayed culling of IPs significantly increased both the cumulative IP incidence and epidemic duration. Contingency management should therefore focus mainly on improving conventional strategies, by increasing disease awareness and communication with stakeholders and preparedness of culling teams in countries with a livestock structure similar to Switzerland; however, emergency vaccination should be considered if there are reasons to believe that the epidemic may become extensive, such as when disease detection has been delayed and many IPs are discovered at the beginning of the epidemic. PMID- 24211106 TI - Identifying and measuring stakeholder preferences for disease prioritisation: A case study of the pig industry in Australia. AB - We describe stakeholder preference modelling using a combination of new and recently developed techniques to elicit criterion weights to incorporate into a multi-criteria decision analysis framework to prioritise exotic diseases for the pig industry in Australia. Australian pig producers were requested to rank disease scenarios comprising nine criteria in an online questionnaire. Parallel coordinate plots were used to visualise stakeholder preferences, which aided identification of two diverse groups of stakeholders - one group prioritised diseases with impacts on livestock, and the other group placed more importance on diseases with zoonotic impacts. Probabilistic inversion was used to derive weights for the criteria to reflect the values of each of these groups, modelling their choice using a weighted sum value function. Validation of weights against stakeholders' rankings for scenarios based on real diseases showed that the elicited criterion weights for the group who prioritised diseases with livestock impacts were a good reflection of their values, indicating that the producers were able to consistently infer impacts from the disease information in the scenarios presented to them. The highest weighted criteria for this group were attack rate and length of clinical disease in pigs, and market loss to the pig industry. The values of the stakeholders who prioritised zoonotic diseases were less well reflected by validation, indicating either that the criteria were inadequate to consistently describe zoonotic impacts, the weighted sum model did not describe stakeholder choice, or that preference modelling for zoonotic diseases should be undertaken separately from livestock diseases. Limitations of this study included sampling bias, as the group participating were not necessarily representative of all pig producers in Australia, and response bias within this group. The method used to elicit criterion weights in this study ensured value trade-offs between a range of potential impacts, and that the weights were implicitly related to the scale of measurement of disease criteria. Validation of the results of the criterion weights against real diseases - a step rarely used in MCDA - added scientific rigour to the process. The study demonstrated that these are useful techniques for elicitation of criterion weights for disease prioritisation by stakeholders who are not disease experts. Preference modelling for zoonotic diseases needs further characterisation in this context. PMID- 24211107 TI - Toxicity of the micropollutants Bisphenol A, Ciprofloxacin, Metoprolol and Sulfamethoxazole in water samples before and after the oxidative treatment. AB - The amount of organic micropollutants detected in surface waters increases steadily. Common waste water treatment plants are not built to remove these substances. Thus there is a need for new technologies. A promising technology is the use of advanced oxidation processes through which organic micropollutants can be removed from waste water. However, the formation of oxidation by-products is likely and needs to be investigated since the by-products not only differ from their parent compounds in regard to their chemical and physical properties but they can also differ in toxicity. Therefore this study was designed to combine chemical and toxicological analyses of the advanced oxidation (O3 [5mg/L] or UV/H2O2 [Hg-LP lamp; 15W; 1g/L H2O2]) of waste water treatment plant effluents and pure water. Effluent samples from conventional activated sludge waste water treatment (mechanical treatment, activated sludge basin, and primary as well as secondary treatment steps) and high-purity deionized water (pure water) were spiked with Bisphenol A, Ciprofloxacin, Metoprolol or Sulfamethoxazole and treated with O3 or UV/H2O2. For the toxicological analyses mammalian cells (CHO 9, T47D) were exposed to the water samples for 24h and were tested for cytotoxicity (MTT Test), genotoxicity (Alkaline Comet Assay) and estrogenicity (ER Calux((r))). The results indicate that the oxidative treatment (O3 or UV/H2O2) of Bisphenol A, Metoprolol, Sulfamethoxazole or Ciprofloxacin in waste water did not result in toxic oxidation by-products, whereas the UV/H2O2 treatment of Bisphenol A and Ciprofloxacin in pure water resulted in by-products with cytotoxic but no estrogenic effects after 60min. PMID- 24211108 TI - [Is a patient's knowledge of cardiovascular risk factors better after the occurrence of a major ischemic event? Survey of 135 cases and 260 controls]. AB - AIM: We hypothezised that patients (cases) who are hospitalized for a major ischemic event--myocardial infarction, stroke, decompensation of peripheral arterial disease--acquire better knowledge than a control population- atheromatous patients without a major ischemic event, patients consulting for a vein disease or a diabetes evaluation, and accompanists--about cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) and have a better understanding of the usefulness of making changes in their lifestyle (quit smoking, regular exercise, Mediterranean diet, low salt diet, weight control, diabetes care). METHODS: A questionnaire was proposed at vascular surgery consultations and vascular and cardiac functional explorations, at the M Pavillon of the Edouard-Herriot hospital, Lyon, France. In five months, 395 questionnaires (135 cases and 260 controls) were analyzed. RESULTS: The global knowledge score was statistically higher for cases than for controls (cases 3.23+/-1.81; controls 2.77+/-2.03; P=0.037). Cases did not abide by monitoring and dietary rules better, except as regards the management of diabetes. Regular physical activity was statistically more prevalent among controls than among cases. Cases mainly received their information from their doctors (general practitioner for 59% of controls and 78% of cases, cardiologist for 25% of controls and 57% of cases) while controls got their information more through magazines or advertising. CONCLUSION: Our results show that after a major ischemic event, cases' knowledge of risk factors is better than the rest of the population without improved rules lifestyle changes. This suggests the usefulness of evaluating a therapeutic education program for atheromatous disease. PMID- 24211109 TI - Mutation in the first Ig-like domain of Kit leads to JAK2 activation and myeloproliferation in mice. AB - Myeloproliferative neoplasms constitute a group of hematopoietic neoplasms at the myeloid stem cell level. Although mutations in the receptor tyrosine kinase KIT have been identified in patients with myeloproliferative neoplasm, the functional causality is unknown because of a lack of animal models. Here, we describe a mouse strain harboring a point mutation in the first Ig-like domain of Kit. Intriguingly, the mutant mice develop a myeloproliferative disorder with typical loss-of-function phenotypes in other tissues. The mutant Kit is incompletely N glycosylated, shows compromised receptor dimerization, and down-regulates Akt and extracellular signal-regulating kinase 1/2 signaling. However, the mutation increases the association of Kit to Janus kinase (JAK)2 and hence the activation of JAK2. The beta common receptor of the gp140 family interacts and synergizes with Kit to promote JAK2 phosphorylation, which is further enhanced by the Kit mutation. Inhibition of JAK2 suppresses the proliferation of hematopoietic progenitors in vitro and partially rescues myeloproliferation in mice. Our data suggest that overactivation of JAK2 leads to myeloproliferation in Kit mutant mice and provide mechanistic insights for the diagnosis and treatment of myeloproliferative neoplasms in humans. PMID- 24211110 TI - Ras-Mek-Erk signaling regulates Nf1 heterozygous neointima formation. AB - Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor-suppressor gene, which encodes neurofibromin, a negative regulator of diverse Ras signaling cascades. Arterial stenosis is a nonneoplastic manifestation of NF1 that predisposes some patients to debilitating morbidity and sudden death. Recent murine studies demonstrate that Nf1 heterozygosity (Nf1(+/-)) in monocytes/macrophages significantly enhances intimal proliferation after arterial injury. However, the downstream Ras effector pathway responsible for this phenotype is unknown. Based on in vitro assays demonstrating enhanced extracellular signal-related kinase (Erk) signaling in Nf1(+/-) macrophages and vascular smooth muscle cells and in vivo evidence of Erk amplification without alteration of phosphatidylinositol 3-kinase signaling in Nf1(+/-) neointimas, we tested the hypothesis that Ras-Erk signaling regulates intimal proliferation in a murine model of NF1 arterial stenosis. By using a well-established in vivo model of inflammatory cell migration and standard cell culture, neurofibromin-deficient macrophages demonstrate enhanced sensitivity to growth factor stimulation in vivo and in vitro, which is significantly diminished in the presence of PD0325901, a specific inhibitor of Ras-Erk signaling in phase 2 clinical trials for cancer. After carotid artery injury, Nf1(+/-) mice demonstrated increased intimal proliferation compared with wild-type mice. Daily administration of PD0325901 significantly reduced Nf1(+/-) neointima formation to levels of wild-type mice. These studies identify the Ras-Erk pathway in neurofibromin-deficient macrophages as the aberrant pathway responsible for enhanced neointima formation. PMID- 24211111 TI - Pulmonary endothelial protein kinase C-delta (PKCdelta) regulates neutrophil migration in acute lung inflammation. AB - Excessive neutrophil migration across the pulmonary endothelium into the lung and release of oxidants and proteases are key elements in pathogenesis of acute lung injury. Previously, we identified protein kinase C-delta (PKCdelta) as an important regulator of proinflammatory signaling in human neutrophils and demonstrated that intratracheal instillation of a TAT-conjugated PKCdelta inhibitory peptide (PKCdelta-TAT) is lung protective in a rat model of sepsis induced indirect pulmonary injury (cecal ligation and puncture). In the present study, intratracheal instillation of this PKCdelta inhibitor resulted in peptide distribution throughout the lung parenchyma and pulmonary endothelium and decreased neutrophil influx, with concomitant attenuation of sepsis-induced endothelial ICAM-1 and VCAM-1 expression in this model. To further delineate the role of PKCdelta in regulating neutrophil migration, we used an in vitro transmigration model with human pulmonary microvascular endothelial cells (PMVECs). Consistent with in vivo findings, inhibition of PMVEC PKCdelta decreased IL-1beta-mediated neutrophil transmigration. PKCdelta regulation was stimulus-dependent; PKCdelta was required for transmigration mediated by IL-1beta and fMLP (integrin-dependent), but not IL-8 (integrin-independent). PKCdelta was essential for IL-1beta-mediated neutrophil adherence and NF-kappaB-dependent expression of ICAM-1 and VCAM-1. In PMVECs, IL-1beta-mediated production of ROS and activation of redox-sensitive NF-kappaB were PKCdelta dependent, suggesting an upstream signaling role. Thus, PKCdelta has an important role in regulating neutrophil-endothelial cell interactions and recruitment to the inflamed lung. PMID- 24211113 TI - Postoperative patency of the retrograde internal mammary vein anastomosis in free flap transfer. AB - BACKGROUND AND AIM: A caudal limb of the internal mammary vein (IMV) can be used as an additional venous drainage route in free flap transfer. However, there remains the possibility that unrecognised occlusion of the retrograde IMV occurs in the early postoperative period due to non-physiologic flow, thus affecting venous drainage. There are no reports regarding the postoperative patency rates of the anastomosed retrograde IMV. This study aimed to clarify the efficacy of the retrograde IMV as an additional venous drainage route in the case of two-vein anastomosis in free flap transfer. PATIENTS AND METHODS: We performed a hospital based prospective case series study to clarify the patency rates of retrograde IMV anastomoses as an additional venous drainage route in cases of two-vein anastomosis in free flap transfer. Both antegrade and retrograde IMV anastomoses were performed in patients who underwent free flap transfer using the IMV as a recipient vein. The postoperative flow vector and peak blood velocity of the retrograde IMV anastomosis were examined using two-dimensional phase contrast magnetic resonance imaging (2D PC-MRI) and colour Doppler imaging. RESULT: A total of five retrograde IMV anastomoses in five patients were performed in the study period. The postoperative patency rate of the retrograde IMV was 60%. In the patent group, the postoperative peak venous blood velocity of the retrograde IMV was significantly slower than that of the antegrade IMV (4.6 +/- 0.5 vs 7.2 +/- 0.8 cm s(-1), P < 0.05). CONCLUSION: We described the postoperative patency rate of retrograde IMV anastomosis in cases of two-vein anastomosis in free flap transfer. Further study is needed to evaluate the reliability of the retrograde IMV as an additional venous drainage route. PMID- 24211112 TI - A pilot test of an integrated self-care intervention for persons with heart failure and concomitant diabetes. AB - Studies show 30% to 47% of people with heart failure (HF) have concomitant diabetes mellitus (DM). Self-care for persons with both of these chronic conditions is conflicting, complex, and often inadequate. This pilot study tested an integrated self-care program for its effects on HF and DM knowledge, self-care efficacy, self-care behaviors, and quality of life (QOL). Hospitalized HF-DM participants (N = 71) were randomized to usual care or intervention using a 1:2 allocation and followed at 30 and 90 days after intervention. Intervention was an integrated education and counseling program focused on HF-DM self-care. Variables included demographic and clinical data, knowledge about HF and DM, HF- and DM specific self-efficacy, standard HF and DM QOL scales, and HF and DM self-care behaviors. Analysis included descriptive statistics, multilevel longitudinal models for group and time effects, post hoc testing, and effect size calculations. Sidak adjustments were used to control for type 1 error inflation. The integrated HF-DM self-care intervention conferred effects on improved HF knowledge (30 days, p = .05), HF self-care maintenance (30 and 90 days, p < .001), HF self-care management (90 days, p = .05), DM self-efficacy (30 days, p = .03; 90 days, p = .004), general diet (30 days, p = .05), HF physical QOL (p = .04), and emotional QOL scores (p = .05) at 90 days within the intervention group. The participants in the usual care group also reported increased total and physical QOL. Greater percentages of participants in the intervention group improved self reported exercise between 0 and 30 days (p = .005 and moderate effect size ES = .47) and foot care between 0 and 90 days (p = .03, small ES = .36). No group differences or improvements in DM-specific QOL were observed. An integrated HF-DM self-care intervention was effective in improving essential components of self-care and had sustained (90 day) effects on selected self-care behaviors. Future studies testing HF-DM integrated self-care interventions in larger samples with longer follow-up and on other outcomes such as hospitalization and clinical markers are warranted. PMID- 24211114 TI - Nasalance scores for normal Korean-speaking adults and children. AB - There are numerous nasometric studies to date, including normative nasalance scores for various languages as well as nasometric differences in age, gender, race and region except the Korean language. In this regard, we sought to establish normative nasalance scores for Koreans. We created speech samples based on the everyday use of phonemes in the Korean language which were syntactically simple for children. In addition, we analysed nasometric features based on age and gender and confirmed test-retest reliability. The study included 108 children (54 girls and 54 boys, aged 7-11 years) and 108 adults (54 women and 54 men, aged 18-29 years) with normal articulation, resonance, voice and hearing. Nasometer II 6400 was used to measure the nasalance scores. The subjects read or repeated three speech stimuli, each consisting of 33, 36 and 24 syllables: (1) an oral passage devoid of nasal consonants, (2) an oro-nasal passage and (3) nasal sentences. For each stimulus, mean nasalance scores were obtained and gender or age dependence was analysed, using two-way analyses of variance. The mean nasalance scores for the oral passage, oro-nasal passage and nasal sentences were 11.69% (standard deviation (SD) 3.68), 34.04% (SD 4.88) and 63.72% (SD 6.07), respectively. Female speakers exhibited significantly higher nasalance scores than male speakers on the oro-nasal passage (p = 0.000) and nasal sentences (p = 0.004). Children exhibited significantly higher nasalance scores than adults on nasal sentences (p = 0.000). The nasalance scores in children and females were a little higher. Korean normative data will provide reference information in the evaluation and treatment of resonance problems. PMID- 24211115 TI - The use of a microscope with near-infrared imaging function in indocyanine green lymphography and lymphaticovenous anastomosis. AB - BACKGROUND: Indocyanine green (ICG) lymphography has become an important investigation in lymphaticovenous anastomosis (LVA). Near-infrared (NIR) imaging systems are available in the market for the production of ICG lymphography. These machines, however, may be difficult to obtain owing to their costs. In our institute, these NIR imaging devices are not available. Alternatively, microscopy with NIR imaging function was used for LVA. The experiences of the production of ICG lymphography with an NIR microscope are described. METHODS: For the production of preoperative ICG lymphography, ICG solution was injected subdermally to the web spaces of the lymphoedema limb. The NIR mode of the microscope was used for the lymphatic mapping. Black and white images and videos of the ICG lymphography were then produced. Intra-operatively, the NIR function was used for the localisation of lymphatic vessels and confirmation of the patency of the LVA. RESULTS: Between February 2013 and May 2013, 24 ICG lymphographies were performed in 20 female patients as a preoperative investigation for LVA. All four ICG lymphography patterns (linear, splash, stardust and diffuse patterns) were demonstrated. CONCLUSIONS: In institutes where NIR imaging devices are not available, we believe that a microscope with an NIR imaging function is a reasonable alternative for the production of ICG lymphography. PMID- 24211116 TI - Shoulder silhouette and axilla reconstruction with free composite elbow tissue transfer following interscapulothoracic amputation. AB - Interscapulothoracic amputation (ISTA) encompasses the removal of the upper limb, scapula and clavicle. As the reconstructive and oncologic limb-saving techniques improved, the indications for this formidable procedure decreased. However, it is still the appropriate procedure in cases with extensive oncologic or traumatic involvement of the shoulder girdle. Following ISTA, the surgeon is not only faced with a large defect but also with severe functional and aesthetic impairments. A solution to these problems is the immediate reconstruction with a free composite transfer from the amputated extremity. We successfully treated three oncologic cases and one traumatic case using this technique. The recipient vessels included the subclavian artery and vein in three cases and the internal thoracic vessels in one case. After a mean follow-up time of 4.5 years, two of the three tumour patients were free of recurrent disease. In all cases stable wound closure was achieved. Three out of four patients would opt for surgery again, in spite of the high occurrence of complications. One patient died after a 14-year event-free postoperative course. We conclude that the defect following ISTA can be successfully covered using a free composite tissue transfer of the amputated disease-free elbow and forearm, while simultaneously reconstructing the shoulder silhouette and axilla. This procedure reduces functional and aesthetic impairments and improves the quality of life. PMID- 24211117 TI - Multiple-digit resurfacing using a thin latissimus dorsi perforator flap. AB - Traumatic digit defects of high complexity and with inadequate local tissue represent challenging surgical problems. Recently, perforator flaps have been proposed for reconstructing large defects of the hand because of their thinness and pliability and minimal donor site morbidity. Here, we illustrate the use of thin latissimus dorsi perforator flaps for resurfacing multiple defects of distal digits. We describe the cases of seven patients with large defects, including digits, circumferential defects and multiple-digit defects, who underwent reconstruction with thin latissimus dorsi perforator flaps between January 2008 and March 2012. Single-digit resurfacing procedures were excluded. The mean age was 56.3 years and the mean flap size was 160.4 cm(2). All the flaps survived completely. Two patients had minor complications including partial flap loss and scar contracture. The mean follow-up period was 11.7 months. The ideal flap for digit resurfacing should be thin and amenable to moulding, have a long pedicle for microanastomosis and have minimal donor site morbidity. Thin flaps can be harvested by excluding the deep adipose layer, and their high pliability enables resurfacing without multiple debulking procedures. The latissimus dorsi perforator flap may be the best flap for reconstructing complex defects of the digits, such as large, multiple-digit or circumferential defects, which require complete wrapping of volar and dorsal surfaces. PMID- 24211118 TI - Complications following body contouring surgery after massive weight loss: a meta analysis. AB - BACKGROUND: Bariatric surgery is a way to achieve lasting weight loss in the obese. Body contouring surgery seeks to alleviate some of the discomfort caused by the excessive loose skin following massive weight loss. Higher complication rates are described in this type of surgery when done post-bariatric. The purpose of this article is to compare complication rates of body contouring surgery when performed on patients with weight loss due to bariatric surgery compared to patients who lost weight due to dietary changes and/or exercise. METHODS: A total of 253 studies were identified by searches in PubMed/Medline databases as well as two hand-search strategies. Three levels of screening resulted in seven studies being considered suitable for inclusion in the meta-analysis. All statistical calculations were performed with Review Manager (RevMan) Version 5.2.3. RESULTS: The fixed-effects pooled risk ratio (RR) of developing complications after body contouring surgery when comparing post-bariatric and non-bariatric patients is 1.60 (95% confidence interval (CI) 1.30-1.96; P < 0.00001; I(2) = 48%) showing that there is a 60% increase in the risk of developing complications if the patient lost weight due to surgery. A subgroup analysis of studies with patients only having one body contouring procedure shows an 87% higher increase in the risk of developing a complication when being post-bariatric (RR = 1.87; 95% CI 1.46-2.40; P < 0.00001; I(2) = 0%). If we exclusively look at the studies with a less uniform patient population that included patients who had one procedure performed as well as patients who had several procedures performed, there seems to be a non-significant 4% lower risk of developing a complication in the case of post-bariatric patients compared to the non-bariatric patients (RR = 0.96; 95% CI 0.65-1.42; P = 0.84; I(2) = 0%). CONCLUSION: The analysis shows a 60-87% increased risk of complications in the post-bariatric group compared to the non bariatric group with statistical significance. PMID- 24211119 TI - Emergence of vancomycin-resistant enterococci in the palliative care setting-how to strike the right balance in infection control measures? PMID- 24211120 TI - The mechanics behind cell division. AB - It is now well established that the orientation of the plane of cell division highly depends on cell geometry in plants. However, the related molecular mechanism remains largely unknown. Recent data in animal systems highlight the role of the cytoskeleton response to mechanical stress in this process. Interestingly, these results are consistent with some data obtained in parallel in plants. Here we review and confront these studies, across kingdoms, and we explore the possibility that the intrinsic mechanical properties of the cytoskeleton play a key role in the nexus between cell division and mechanical stress. This opens many avenues for future research that are also discussed in this review. PMID- 24211121 TI - Radiation pneumonitis after breast-conserving surgery for cancer. PMID- 24211122 TI - Dosimetric and clinical outcome in image-based high-dose-rate interstitial brachytherapy for anal cancer. AB - PURPOSE: To evaluate dosimetric and clinical outcome in patients of anal cancer treated with image-based interstitial high-dose-rate brachytherapy following chemoradiation. METHODS AND MATERIALS: Sixteen patients with anal cancer were treated with chemoradiation followed by brachytherapy boost with image-based high dose-rate interstitial brachytherapy from January 2007 to June 2011. Two brachytherapy dose schedules were used: 21 Gy in seven fractions and 18 Gy in six fractions depending on response to chemoradiation. CT scan was done after placement of needles for confirmation of placement and treatment planning. Target volume was contoured on CT scans. Volumetric quality indices and dose parameters were calculated. RESULTS: The mean clinical target volume was 17.7 +/- 4.98 cm(3), and the median overall tumor size was 4.2cm (3.4-5cm). The mean values of coverage index, dose homogeneity index, overdose volume index, dose non uniformity ratio, and conformal index were 0.94, 0.83, 0.21, 0.37, and 0.88, respectively. With a median followup of 41 months (range, 20-67.2 months), preservation of the anal sphincter was achieved in 14 patients. The 1- and 2-year local control rates were 93.8% and 87.5%, respectively. Treatment was well tolerated and none of the patients developed Grade 3 or higher late toxicity. CONCLUSIONS: The combination of external beam radiotherapy with interstitial brachytherapy increases the dose to the tumor volume and limits the volume of irradiated normal tissue, thereby decreasing late toxicity. The use of image based treatment planning provides better dose conformality with reduced toxicity and helps to prevent a geographic miss. PMID- 24211123 TI - Re-irradiation with interstitial pulsed-dose-rate brachytherapy for unresectable recurrent head and neck carcinoma. AB - PURPOSE: To assess the long-term results of protocol-based interstitial pulsed dose-rate (PDR) brachytherapy combined with simultaneous chemotherapy in selected patients with recurrent head and neck tumors not amenable to salvage surgery. METHODS AND MATERIALS: A total of 51 patients with recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Forty patients (78%) had salvage brachytherapy alone using a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) using a median total dose of DREF=27 Gy. Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. The analysis was performed after a median followup of 58 months. RESULTS: Local control rates calculated according to Kaplan-Meier after 2 and 5 years were 71% and 57%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrence-free survival rates were 78.9% vs. 38.5% (p=0.01), respectively. No other patient or treatment-related parameters had a significant influence on treatment results. A total of 9/51 (17.7%) and 6/51 (11.8%) patients developed soft-tissue necrosis or bone necrosis, respectively, but only 2% of patients required surgical treatment. CONCLUSIONS: PDR interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery. PMID- 24211124 TI - Correlates of emotional congruence with children in sexual offenders against children: a test of theoretical models in an incarcerated sample. AB - Emotional congruence with children is a psychological construct theoretically involved in the etiology and maintenance of sexual offending against children. Research conducted to date has not examined the relationship between emotional congruence with children and other psychological meaningful risk factors for sexual offending against children. The current study derived potential correlates of emotional congruence with children from the published literature and proposed three models of emotional congruence with children that contain relatively unique sets of correlates: the blockage, sexual deviance, and psychological immaturity models. Using Area under the Curve analysis, we assessed the relationship between emotional congruence with children and offense characteristics, victim demographics, and psychologically meaningful risk factors in a sample of incarcerated sexual offenders against children (n=221). The sexual deviance model received the most support: emotional congruence with children was significantly associated with deviant sexual interests, sexual self-regulation problems, and cognition that condones and supports child molestation. The blockage model received partial support, and the immaturity model received the least support. Based on the results, we propose a set of further predictions regarding the relationships between emotional congruence with children and other psychologically meaningful risk factors to be examined in future research. PMID- 24211125 TI - Histological characteristics of induced membranes in subcutaneous, intramuscular sites and bone defect. AB - BACKGROUND: The induced membrane technique was proposed as a treatment of large segmental bone defects. The influence of the surrounding tissues on its characteristics remains unknown. It is therefore not known which kind of plastic surgery procedure (muscular or facio-cutaneous flap) would optimize bone osteointegration within a bone defect reconstructed using the induced-membrane technique. HYPOTHESIS: We hypothesized that membrane characteristics could be influenced by the soft-tissue environment either subcutaneous or muscular. OBJECTIVE: To evaluate the histological characteristics of poly methylmethacrylate (PMMA) induced membranes in intramuscular, subcutaneous and bony environment (radius defects) at 2 steps: spacer implantation; secondary bone graft and its subsequent osteintegration after spacer removal. METHODS: PMMA induced membranes were obtained in the three sites of 15 rabbits. Subsequent new bone formation was studied in the same environments in 24 other rabbits. Six weeks after the initial implantation, PMMA spacers were replaced with iliac autografts. Animals were euthanized at 2, 4, and 8 weeks postoperatively. Tissue samples were harvested and stained with hematoxylin and eosin. The histological characteristics of the membrane (thickness and microvessel density) and the newly formed bone (cortical thickness) were quantitatively analyzed. RESULTS: The membranes in the subcutaneous sites developed quicker, were thicker and had the lowest microvessel density (P<0.01). The membranes in the intramuscular sites developed later and were thinner (P<0.01). The membranes in the osseous defects had the greatest microvessel density (P<0.01). After bone grafting, induced membranes became thinner and their microvessel density decreased substantially, but maintained better in osseous site. The newly-formed bone that developed in the radius defects, had the thickest cortices (P<0.01). CONCLUSIONS: The evolution of membranes induced in the intramuscular and subcutaneous environments was close to that of the bone defect model, although bone formation appeared weaker. PMID- 24211126 TI - Isolated anterior interosseous nerve deficit due to a false aneurysm of the humeral artery: an unusual complication of penetrating arm injury. Case report and literature review. AB - Anterior interosseous nerve (AIN) injuries account for only 1% of all the nerve injuries at the upper limb. We report the case of a 22-year-old male who sustained a penetrating injury to the arm. No neurological deficit was found at the initial evaluation. However, 6 weeks later, he had a motor deficit confined to the territory of the AIN with weakness of the flexor pollicis longus and flexor digitorum longus to the index. He also reported paraesthesia. Tinel's test was positive over the pinpoint wound in the arm, where a painful swelling was felt. Electroneurophysiological testing indicated a deficit of the AIN. Surgical exploration identified a thrombosed false aneurysm of the humeral artery responsible for compression of the median nerve. One month later, the patient had achieved a full recovery. Immediate routine exploration of deep penetrating wounds, although mandatory, may fail to detect any lesions. Close monitoring must be provided subsequently, as gradual nerve compression can result in delayed neurological deficits. PMID- 24211127 TI - High rate of fracture in the cementless modular ExtremeTM (Mark I) femoral prosthesis in revision total hip arthroplasty: 33 cases at more than 5 years' follow-up. AB - INTRODUCTION: The modular concept has been recommended in femoral revision surgery with extensive bone loss, but entails mechanical complications: disassembly and fracture. The present retrospective study assessed the Mark I ExtremeTM modular prosthesis at a minimum 5 years' follow-up. HYPOTHESIS: A cementless modular femoral stem facilitates revision in case of extensive bone loss, providing satisfactory results without risk of junction failure. MATERIALS AND METHODS: Thirty-three prostheses presenting aseptic loosening, including 3 with periprosthetic fracture, in 23 female and 9 male patients, with a mean age of 65 years (range, 49-83 years), were reviewed at a mean 6.3 years' follow-up (range, 5-9 years). Bone loss was assessed on the SOFCOT (17/33 grade 3 or 4) and Paprosky classifications (19/33 grade III or IV). One patient died; another was lost to follow-up, leaving 31 hips for analysis. Clinical assessment comprised Postel Merle d'Aubigne (PMA) and Harris Hip scores (HHS); radiological assessment used the Engh score and corticomedullary index (CMI). RESULTS: There were 15 complications requiring surgery: 9 (27%) unrelated to the implant (1 hematoma, 2 infections, 2 dislocations, 1 femoral non-union, 3 asymptomatic trochanteric non unions) and 6 (18%) implant-related (four 3-level fractures and 2 epiphyseal metaphyseal disassemblies, requiring 3 total exchanges and 3 proximal component replacements). PMA and HHS scores showed significant improvement, PMA rising from 10.4 (6-18) to 14.4 (11-18) and HHS from 50 (19-88) to 80.9 (52-100). Bone regrowth was "certain" on the Engh classification in 11 cases (44%). There was no diaphyseal component subsidence, even in case of fracture or dissociation. CMI at the 3 junctions between the 4 quarters of the stem showed no significant change: 32.9 and 32.7, 41.2 and 38.7, and 41.6 and 39.9 respectively. Six-year survivorship was 81% (95% CI: 68-94%). DISCUSSION: In other series for the same type of implant, the rates of fracture (always metaphyseal-diaphyseal) were much lower: 0.8-3.8%. This stem ensures diaphyseal fixation in case of extensive bone loss, but incurs excessive risk of disassembly and fracture. PMID- 24211128 TI - Rotator cuff tears after 70 years of age: a prospective, randomized, comparative study between decompression and arthroscopic repair in 154 patients. AB - INTRODUCTION: Arthroscopic repair of rotator cuff tears leads to better clinical outcomes than subacromial decompression alone; however the former is rarely proposed to patients above 70 years of age. Our hypothesis was that arthroscopic repair would be superior to decompression in patient 70 years or older. The primary goal was to compare the clinical results obtained with each technique. The secondary goal was to analyze the effects of age, tendon retraction and fatty infiltration on the outcome. METHODS: This was a prospective, comparative, randomized, multicenter study where 154 patients were included who were at least 70 years of age. Of the included patients, 143 (70 repair and 73 decompression) were seen at one-year follow-up; these patients had an average age of 74.6 years. Shoulders had a complete supraspinatus tear with extension limited to the upper third of the infraspinatus and Patte stage 1 or 2 retraction. Clinical outcomes were evaluated with the Constant, ASES and SST scores. RESULTS: All scores improved significantly with both techniques: Constant +33.81 (P<0.001), ASES +52.1 (P<0.001), SST +5.86 (P<0.001). However, repair led to even better results than decompression: Constant (+35.85 vs. +31.8, P<0.05), ASES (+56.09 vs. +48.17, P=0.01), SST (+6.33 vs. +5.38, P=0.02). The difference between repair and decompression was not correlated with age; arthroscopic repair was also better in patients above 75 years of age (Constant, ASES and SST scores P<0.01). There was no significant correlation between the final outcomes and initial retraction: Constant (P=0.14), ASES (P=0.92), SST (P=0.47). The difference between repair and decompression was greater in patients with stages 0 and 1 fatty infiltration (Constant P<0.02) than in patients with stages 2 and 3 fatty infiltration (Constant P<0.05). CONCLUSION: There was a significant improvement in all clinical scores for both techniques 1 year after surgery. Repair was significantly better than decompression for all clinical outcomes, even in patients above 75 years of age. The difference observed between repair and decompression was greater in patients with more retracted tears and lesser in patients with more severe fatty infiltration. PMID- 24211129 TI - Rotator cuff tear imaging in patients over 70 years: specific MRI findings? AB - BACKGROUND: During the symposium held by the French Arthroscopy Society on rotator cuff tears in patients over 70 years of age, the absence of studies into potential specific pathological features in this age group was pointed out. Here, our main objective was to describe magnetic resonance imaging (MRI) findings in this patient population. HYPOTHESIS: Tendons and muscles are smaller, lamellar dissection more prominent, and dystrophic changes more marked in patients over 70 years of age. MATERIAL AND METHOD: We retrospectively studied 50 patients with isolated supraspinatus tears, including 25 younger than 50 and 25 older than 70 years of age. Tear size and retraction were evaluated according to Patte; tendon thickness, lamellar dissection, and fatty infiltration according to Goutallier; muscle size according to Thomazeau; and the tangent sign according to Zanetti. RESULTS: In contradiction to our study hypothesis, lateral tendon thickness was similar in the two age groups. Medial thickness of the tendon-muscle junction, however, was greater in the younger group. Lamellar dissection was more marked and fatty infiltration more severe in the older group. As expected, marked muscle wasting and a positive tangent sign were noted in over two-thirds of patients in the older group. CONCLUSION: This preliminary study in a small number of patients identified specific MRI features of supraspinatus tears in patients older than 70 years compared to younger patients. A larger study would be useful to confirm these findings. PMID- 24211130 TI - Spinal-epidural hematoma presenting as paraplegia following mitral valve surgery: a case report. PMID- 24211131 TI - Frequency of acute worsening events in fibrotic pulmonary sarcoidosis patients. AB - Patients with fibrotic sarcoidosis can develop worsening of pulmonary symptoms for various reasons. We studied acute worsening events defined as episodes treated with limited courses of either antibiotics and or increased corticosteroid doses which resolved within four weeks. The prevalence of acute worsening events in patients with fibrotic sarcoidosis was investigated. Of 740 sarcoidosis patients seen in our clinic over a four month period, 129 (17%) had fibrotic sarcoidosis. We noted the age, race, gender, computer tomography (CT) results, and pulmonary function as measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the FEV1/FVC ratio. In a retrospective manner, the fibrotic sarcoidosis patients reported a median of three acute worsening events (range zero to eight) in the prior year. Bronchiectasis was noted on CT imaging in 63 of 129 (49%) of the fibrotic sarcoidosis patients. Fibrotic sarcoidosis patients reported a higher frequency of acute worsening events (3 (0-6)) than those without bronchiectasis (2 (0-8), p = 0.0001). Sixteen patients receiving anti-tumor necrosis factor antibodies reported a higher frequency of acute worsening events compared to those not receiving anti-tumor necrosis factor antibodies (p = 0.0297). There was no relationship between the number of acute worsening events and race, gender, smoking history, or FVC, FEV1, or FEV1/FVC ratio. We conclude that acute worsening events are frequent in patients with fibrotic sarcoidosis patients and are more common in patients with bronchiectasis and those receiving anti-tumor necrosis factor antibody therapies. PMID- 24211132 TI - Chenopodolans A-C: phytotoxic furopyrans produced by Phoma chenopodiicola, a fungal pathogen of Chenopodium album. AB - Three tetrasubstituted furopyrans, named chenopodolans A-C, were isolated together with the well known fungal metabolite (-)-(R)-6-hydroxymellein from the liquid culture of Phoma chenopodiicola, a fungal pathogen proposed for the biological control of Chenopodium album, a common worldwide weed of arable crops. The structures of chenopodolans A-C were established by spectroscopic and chemical methods as 2-(3-methoxy-2,6-dimethyl-7aH-furo[2,3-b]pyran-4-yl)-butane 2,3-diol, 1-(3-methoxy-2,6-dimethyl-7aH-furo[2,3-b]pyran-4-yl)ethanol and 3 methoxy-2,6-dimethyl-4-(1-methylpropenyl)-7aH-furo[2,3-b]pyran, respectively. The absolute configuration R to the hydroxylated secondary carbon (C-11) of the side chain at C-4 of chenopodolan A was determined by applying an advanced Mosher's method. Assayed by leaf puncture on host and non-host weeds chenopodolans A and B, and the 11-O-acetylchenopodolan A showed a strong phytotoxicity. These results showed that the nature of the side chain attached to C-4 is an important feature for the phytotoxicity. A weak zootoxic activity was only showed by chenopodolan B. PMID- 24211133 TI - Interrater reliability assessment using the Test of Gross Motor Development-2. AB - OBJECTIVES: The aim was to examine interrater reliability of the object control subtest from the Test of Gross Motor Development-2 by live observation in a school field setting. DESIGN: Reliability Study--cross sectional. METHODS: Raters were rated on their ability to agree on (1) the raw total for the six object control skills; (2) each skill performance and (3) the skill components. Agreement for the object control subtest and the individual skills was assessed by an intraclass correlation (ICC) and a kappa statistic assessed for skill component agreement. RESULTS: A total of 37 children (65% girls) aged 4-8 years (M = 6.2, SD = 0.8) were assessed in six skills by two raters; equating to 222 skill tests. Interrater reliability was excellent for the object control subset (ICC = 0.93), and for individual skills, highest for the dribble (ICC = 0.94) followed by strike (ICC = 0.85), overhand throw (ICC = 0.84), underhand roll (ICC = 0.82), kick (ICC = 0.80) and the catch (ICC = 0.71). The strike and the throw had more components with less agreement. CONCLUSIONS: Even though the overall subtest score and individual skill agreement was good, some skill components had lower agreement, suggesting these may be more problematic to assess. This may mean some skill components need to be specified differently in order to improve component reliability. PMID- 24211134 TI - [Recognition of excretory/secretory antigens of Anisakis type I and evolution of IgE in experimentally infected rats]. AB - INTRODUCTION: Anisakis spp., during parasitism, release excretory-secretory antigens that, in contact with the human immune system, can trigger a hypersensitivity response mediated by IgE, causing various allergic symptoms. OBJECTIVES: To evaluate the IgE response in Wistar rats after infection with L3 larvae of the parasite Anisakis spp. METHODS: Some determining factors involved in the technique have been improved in this work, such as: the concentration of polyacrylamide used in the preparation of the gels, the antigen concentration used, and the temperature required for denaturation of proteins. RESULTS: Immune responses (Ag-Ab) observed by the immunoblotting technique showed a greater intensity with serum obtained after reinfection, which have recognized proteins that may correspond to the major antigen Ani s 1 and other polypeptides of interest in the diagnosis of human anisakiasis. CONCLUSION: This paper concludes that immunoblotting is a useful technique to detect IgE antibodies against Anisakis proteins. PMID- 24211135 TI - SAHA enhances Proteostasis of epilepsy-associated alpha1(A322D)beta2gamma2 GABA(A) receptors. AB - GABA(A) receptors are the primary inhibitory ion channels in the mammalian central nervous system. The A322D mutation in the alpha1 subunit of GABA(A) receptors is known to result in its degradation and reduce its cell surface expression, leading to loss of GABAA receptor function in autosomal dominant juvenile myoclonic epilepsy. Here, we show that SAHA, a FDA-approved drug, increases the transcription of the alpha1(A322D) subunit, enhances its folding and trafficking posttranslationally, increases its cell surface level, and restores the GABA-induced maximal current in HEK293 cells expressing alpha1(A322D)beta2gamma2 receptors to 10% of that for wild-type receptors. To enhance the trafficking efficiency of the alpha1(A322D) subunit, SAHA increases the BiP protein level and the interaction between the alpha1(A322D) subunit and calnexin. SAHA is a drug that enhances epilepsy-associated GABAA receptor proteostasis. PMID- 24211136 TI - PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. AB - Phosphoinositide-3 kinase (PI3K)-delta and PI3K-gamma are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-delta and PI3K-gamma inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. We explored the therapeutic value of combined PI3K-delta and PI3K-gamma blockade, and IPI-145 showed potent activity in collagen-induced arthritis, ovalbumin-induced asthma, and systemic lupus erythematosus rodent models. These findings support the hypothesis that inhibition of immune function can be achieved through PI3K-delta and PI3K-gamma blockade, potentially leading to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases. PMID- 24211137 TI - Crystal structures of Sirt3 complexes with 4'-bromo-resveratrol reveal binding sites and inhibition mechanism. AB - Sirtuins are protein deacetylases regulating aging processes and various physiological functions. Resveratrol, a polyphenol found in red wine, activates human Sirt1 and inhibits Sirt3, and it can mimic calorie restriction effects, such as lifespan extension in lower organisms. The mechanism of Sirtuin modulation by resveratrol is not well understood. We used 4'-bromo-resveratrol (5 (2-(4-hydroxyphenyl)vinyl)-1,3-benzenediol) to study Sirt1 and Sirt3 modulation. Despite its similarity to the Sirt1 activator resveratrol, the compound potently inhibited both, Sirt1 and Sirt3. Crystal structures of Sirt3 in complex with a fluorophore-labeled and with a native substrate peptide, respectively, in presence of 4'-bromo-resveratrol reveal two compound binding sites. Biochemical studies identify the internal site and substrate competition as the mechanism for inhibition, providing a drug target site, and homology modeling suggests that the second, allosteric site might indicate the site for Sirt1 activation. PMID- 24211139 TI - Poor survival in prostate cancer patients with primary refractoriness to docetaxel. PMID- 24211140 TI - Pituitary macroadenoma causing symptomatic internal carotid artery compression: surgical treatment through transsphenoidal tumor resection. AB - Pituitary macroadenomas can invade the cavernous sinus and rarely cause occlusion of the internal carotid artery (ICA). Most patients with symptomatic obstruction of the ICA by a pituitary tumor have been reported as a result of apoplexy. The authors review the literature about this condition and report a 48-year-old man who presented with transient ischemic attacks leading to a stroke. Imaging studies demonstrated complete occlusion of the left ICA and critical narrowing of the right ICA at the level of the clinoid processes, most likely due to macroadenoma mass effect. There was no radiologic evidence of apoplexy. Surgical resection of the tumor and ICA decompression via the transsphenoidal route resulted in prevention of further symptoms. Histopathologic analysis confirmed a nonfunctioning pituitary adenoma without evidence of hemorrhage or intratumoral infarction. This patient, to the authors' knowledge, is the first documented patient with symptomatic carotid compression by a pituitary adenoma without evidence of apoplexy. PMID- 24211141 TI - Giant axonal neuropathy diagnosed on skin biopsy. AB - Evaluation of hereditary axonal neuropathy in childhood is complex. Often, the child has to be subjected to general anaesthesia for a nerve biopsy to guide further genetic testing, which may or may not be readily available. We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing. PMID- 24211138 TI - Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington's disease. AB - Protein palmitoylation, a reversible lipid modification of proteins, is widely used in the nervous system, with dysregulated palmitoylation being implicated in a variety of neurological disorders. Described below is ABE/SILAM, a proteomic strategy that couples acyl-biotinyl exchange (ABE) purification of palmitoyl proteins to whole animal stable isotope labeling (SILAM) to provide an accurate tracking of palmitoylation change within rodent disease models. As a first application, we have used ABE/SILAM to look at Huntington's disease (HD), profiling palmitoylation change in two HD-relevant mouse mutants: the transgenic HD model mouse YAC128 and the hypomorphic Hip14-gt mouse, which has sharply reduced expression for HIP14 (Zdhhc17), a palmitoyl-transferase implicated in the HD disease process. Rather than mapping to the degenerating neurons themselves, the biggest disease changes instead map to astrocytes and oligodendrocytes (i.e., the supporting glial cells). PMID- 24211142 TI - Short-term outcome for saccular cerebral aneurysms treated with the Orbit Galaxy Detachable Coil System. AB - Technological advancement within the field of neuroendovascular therapy may lead to safer and more robust treatment options for patients with lesions traditionally not favorable to coil occlusion. We analyze and report our outcomes with the Orbit Galaxy Detachable Coil System (DePuy Synthes, West Chester, PA, USA) for the treatment of anterior and posterior circulation saccular cerebral aneurysms. Patients treated with Orbit Galaxy coils for primary or recurrent saccular cerebral aneurysms from October 2010 to July 2012 were retrospectively reviewed using medical records, operative reports, and radiographs. Ninety-three patients, 69% unruptured and 31% ruptured, were treated with Orbit Galaxy coils for their anterior (80%) or posterior (20%) circulation saccular cerebral aneurysm. Primary treatment with Orbit Galaxy coils occurred in 84% of patients with an initial 100% occlusion rate of 65% while 16% had Galaxy coils placed into a "secondary" recurrent lesion. The overall incidence of recurrence was 26% with a mean interval of 7 months. Retreatment for recurrence was needed in 20 patients (22%). The mortality rate was 0%. A 2% incidence of rebleed was observed; each was after a secondary treatment. The morbidity of the treatment was low with 1% having a modified Rankin score greater than 3. Primary endovascular treatment of saccular cerebral aneurysms of the anterior and posterior circulation with the Orbit Galaxy Detachable Coil System is safe and effective in the short term. PMID- 24211143 TI - Psychosis with obsessive-compulsive symptoms in tuberous sclerosis. AB - We present a case of tuberous sclerosis complex (TSC) diagnosed in adulthood in a man initially referred for specialist neuropsychiatric assessment with psychosis and obsessive-compulsive symptoms (OCS) on a background of epilepsy and intellectual disability. To our knowledge, this is the first reported patient with TSC featuring both psychosis and OCS. This patient highlights the importance of comprehensive re-evaluation of atypical presentations of intellectual disability, epilepsy and associated neuropsychiatric symptoms, even in adulthood. This is particularly relevant in the context of significant advances in genetics, neuroscience, imaging and treatments for heritable neurogenetic disorders. PMID- 24211145 TI - Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: a conceptual framework. AB - Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1alpha (HIF-1alpha) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection. PMID- 24211144 TI - C-reactive protein and long-term ischemic stroke prognosis. AB - C-reactive protein (CRP) is an inflammatory biomarker of inflammation and may reflect progression of vascular disease. Conflicting evidence suggests CRP may be a prognostic biomarker of ischemic stroke outcome. Most studies that have examined the relationship between CRP and ischemic stroke outcome have used mortality or subsequent vascular event as the primary outcome measure. Given that nearly half of stroke patients experience moderate to severe functional impairments, using a biomarker like CRP to predict functional recovery rather than mortality may have clinical utility for guiding acute stroke treatments. The primary aim of this study was to systematically and critically review the relationship between CRP and long-term functional outcome in ischemic stroke patients to evaluate the current state of the literature. PubMed and MEDLINE databases were searched for original studies which assessed the relationship between acute CRP levels measured within 24 hours of symptom onset and long-term functional outcome. The search yielded articles published between 1989 and 2012. Included studies used neuroimaging to confirm ischemic stroke diagnosis, high sensitivity CRP assay, and a functional outcome scale to assess prognosis beyond 30 days after stroke. Study quality was assessed using the REMARK recommendations. Five studies met all inclusion criteria. Results indicate a significant association between elevated baseline high sensitivity CRP and unfavorable long-term functional outcome. Our results emphasize the need for additional research to characterize the relationship between acute inflammatory markers and long-term functional outcome using well-defined diagnostic criteria. Additional studies are warranted to prospectively examine the relationship between high sensitivity CRP measures and long-term outcome. PMID- 24211146 TI - A bioenergetic assessment of mitral regurgitation: a new tool to assess severity? AB - Mitral regurgitation is frequently classified as mild, moderate or severe based on echocardiography. Patients with mild mitral regurgitation are usually managed medically. We hypothesise that mild mitral regurgitation as assessed volumetrically can in fact be severe when analysed from a bioenergetics point of view. The conservation of energy predicts that any regurgitant volume will require the heart to provide more work energy to support the circulation. Mitral regurgitation involves the left ventricle imparting potential energy, via blood pressure, and kinetic energy, via regurgitant velocity, to the regurgitant blood volume. This implies that regurgitant volume, regurgitant velocity, systolic blood pressure, heart rate, regurgitant orifice area and cardiac output are all important factors. We present limited data to demonstrate our hypothesis. A bioenergetic analysis of mitral regurgitation, may identify patients whose mitral regurgitation, assessed via echocardiography as mild, is actually clinically significant. In addition we identify the importance of blood pressure and heart rate control in patients with mitral regurgitation. The concept that a bit of mitral regurgitation in patients with poor left ventricles is a good thing, as it helps offload the left ventricle is from an engineering point fundamentally flawed. PMID- 24211147 TI - Attention Bias Modification Treatment for children with anxiety disorders who do not respond to cognitive behavioral therapy: a case series. AB - Evidence is emerging to support the promise of Attention Bias Modification Treatment (ABMT), a computer-based attention training program, in reducing anxiety in children. ABMT has not been tested as an adjuvant for children with anxiety disorders who do not respond to Cognitive-Behavioral Therapy (CBT). This case series presents findings from an open trial of ABMT among six children (four girls; M age = 11.2 years) who completed a CBT protocol and continued to meet diagnostic criteria for an anxiety disorder. All children completed the ABMT protocol with no canceled or missed sessions. Child self-ratings on anxiety symptoms and depressive symptoms significantly decreased from pretreatment to posttreatment, as did parent ratings on child anxiety-related impairment. Parent ratings on child anxiety and internalizing symptoms displayed non-significant decreases from pretreatment to posttreatment. These findings support the potential promise of ABMT as a feasible adjuvant treatment that reduces anxiety and impairment among child anxiety CBT nonresponders. PMID- 24211149 TI - [Generic substitution in primary care in 2011: differences according to pharmacological classes?]. AB - BACKGROUND: Generic substitution has been permitted for several years in France and is promoted in order to reduce health expenditures. However, reluctance concerning use of generic drugs exists for different reasons: suspicions about their efficacy and/or safety, differences in content (excipients) and discussions about bioequivalency. The aim of our study was to determine whether or not the substitution ratio differs according to pharmacological classes used in primary care. METHODS: We conducted a descriptive study in the French Health Insurance Database using reimbursement data on drugs prescribed and delivered in the Midi Pyrenees administrative district between March 2010 and March 2011. We selected different pharmacological classes largely used in primary care. For each class, a substitution ratio was calculated (DDD of generics delivered/DDD of brand name plus generics). A Chi(2) test was used in order to detect a difference between these substitution ratios. RESULTS: The global substitution ratio was 72.32%. Values varied from 28.36% for thyroid hormones to 90.39% for antibiotics, with significant statistical difference (P<0.001). The substitution ratio was less than 50% for thyroid hormones (28.36%) and antiepileptics (45.28%). Higher substitution ratios were observed for protein pump inhibitors (88.81%), statins (87.81%), antidepressors (87.37%) and diuretics (86.1%). CONCLUSION: This study highlights major differences in terms of the generic substitution ratio between different pharmacological classes. This difference can be explained in part by published guidelines. Further studies are needed to ascertain the precise point of view of patients, general practitioners and pharmacists concerning this issue. PMID- 24211148 TI - Personality disorders and the persistence of anxiety disorders: evidence of a time-of-measurement effect in NESARC. AB - Recent studies using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) have found that some personality disorders (PDs) increase the persistence of several Axis I disorders. However, these effects are potentially confounded with the data collection wave in which PDs were assessed. Our aim was to extend published analyses to the case of anxiety disorders and to determine the robustness of the associations to analyses examining time-of measurement effects. Persistence of anxiety disorders was defined either as follow-up diagnosis among participants diagnosed at baseline ("prediction") or baseline diagnosis among participants diagnosed at follow-up ("post-diction"). Results revealed a robust pattern of higher odds ratios for post-diction among PDs assessed at baseline, and lower odds ratios for post-diction among PDs assessed at follow-up, suggesting a time of measurement artifact. Although only 4% of associations were robust to both predictive and post-dictive analyses, these were consistent with previous research. PMID- 24211150 TI - Screen time, cardiorespiratory fitness and adiposity among school-age children from Monteria, Colombia. AB - OBJECTIVES: To explore the association between electronic media exposure (television viewing time, personal computer/video game use, total screen time), and waist circumference and body mass index, and study whether this association is independent of cardiorespiratory fitness, in a representative sample of adolescents from Monteria, Colombia. DESIGN: Cross-sectional study analyzing data from 546 students aged 11-18 years, from fourteen randomly selected schools. Z scores for WC and BMI were calculated. METHODS: The physical activity module of the Global School Health Survey 2007 was used to determine EME, and the shuttle run test was used to assess CRF. Linear regression models adjusted by age, school location, physical activity level, type of institution (public or private), consumption of sweetened beverages, fast food, and fried food were used. RESULTS: Among boys, independently of cardiorespiratory fitness, high television viewing time (>= 2 h/day) (beta=+0.22; p<0.02), was positively associated with waist circumference. High total screen time (>3h/day) was positively associated with waist circumference (beta=+0.34; p<0.01), and body mass index (beta=+0.39; p<0.01). Among girls, sedentary behavior was not associated with adiposity, but cardiorespiratory fitness (beta=-0.04; p<0.02) was negatively associated with body mass index. CONCLUSIONS: These findings support the evidence on the negative impact of excessive electronic media exposure and low cardiorespiratory fitness, and highlight the need for interventions and prevention strategies. PMID- 24211151 TI - Socioeconomic deprivation independently predicts symptomatic painful diabetic neuropathy in type 1 diabetes. AB - INTRODUCTION: Painful peripheral neuropathy in people with type 1 diabetes is a disabling and costly complication. A greater understanding of predisposing factors and prescribing may facilitate more effective resource allocation. METHODS: The Townsend index of deprivation (numerically higher for greater disadvantage) was examined in the pseudonymised records of 1621 (684 females) individuals with type 1 diabetes and related to prevalence of drug treated severe diabetes related neuropathic pain. RESULTS: Treatment for neuropathic pain was initiated in 280 patients, who were older at 57.1 vs 45.6 years and had greater BMI (29.8 vs 27.8kg/m(2); p<0.0001). HbA1C was similar between groups, whilst eGFR was lower in the neuropathic pain group. Amitriptyline was the most commonly prescribed agent (46.8% of total prescriptions). Duloxetine (60mg daily) was prescribed in 9.3% of cases. There were significant differences between the groups for the Townsend index, with a greater proportion (34.3% vs 21.7%) of patients with treated neuropathic pain having a score of >=1 (X(2)=19.9, p<0.001). Multivariate logistic regression analyses indicated that each unit increment in Townsend index was associated with a 11% increased odds of requiring neuropathic pain treatment [odds ratio (95% CI) 1.11 (1.05-1.17), p<0.001]. This was independent of age: 1.04 (1.02-1.05), BMI: 1.03 (1.01-1.05), HbA1C: 1.15 (1.05-1.24), male gender: 0.74 (0.55-0.98), systolic BP and eGFR. Inclusion of depression and mixed anxiety/depressive disorder did not change the risk estimates. CONCLUSION: Amitriptyline was the most commonly used agent for treatment of diabetes related neuropathic pain with Duloxetine much less used. A higher level of socioeconomic deprivation may predispose to severe neuropathic pain in diabetes. Differential allocation of resources may benefit this group. PMID- 24211152 TI - Childhood cancer in Aden, Yemen. AB - BACKGROUND: Cancer in children is increasingly recognized as a major and growing health problem in different developed and developing countries. In Yemen, it is still difficult to know the extent of cancer and its determinants among children. This study was conducted to determine the magnitude of childhood cancer in Aden and provide the preliminary baseline data by age and sex. METHODS: Basic epidemiologic data was retrieved from all paediatric cancer <15 years age registered in Aden Caner Registry (ACR), Yemen, from 1997 to 2006. RESULTS: The results showed a total of 483 childhood cancers <15 years age comprising 12.7% of all registered malignancies with a male to female ratio of 1.5:1. The predominant age affected was 5-9 years in (38.3%) children. The most frequent cancer among Yemeni children was leukaemia 160 (33.1%) followed by lymphoma 152 (31.5%), CNS tumors 35 (7.2%) and bone tumours 25 (5.2%). An interesting and unusual finding was the frequency of acute myeloid leukaemia twice more common in female (66.7%) than male (33.3%). Lymphoma was the most common cancer in children >5 years. An interesting comparison was the preponderance of non-Hodgkins's lymphoma over Hodgkin's disease (1.6:1) stronger in female (3:1) than male (1.25:1). Medulloblastoma was the most common CNS tumour followed by astrocytoma, an infrequent finding in childhood cancer. Osteosarcoma was the most frequent bone tumour (male:female ratio of 1.8:1). A female preponderance was noticed in chondrosarcoma that was not yet documented. The blastoma group was common in younger age group. Retinoblastoma and nephroblastoma predominated in female while neuroblastoma, hepatoblastoma and soft tissue sarcomas in male. CONCLUSION: It is concluded that there is a lower frequency of childhood cancer in Aden when compared with developed countries. It may explained by the fact that a large number of childhood cancers remain undiagnosed due to limitations of diagnostic facilities or under registration. Central paediatric hospitals should be provided with essential diagnostic and therapeutic services that should be freely available to all children with cancer. PMID- 24211153 TI - Patient navigation pathway and barriers to treatment seeking in cancer in India: a qualitative inquiry. AB - Cancer is a leading cause of mortality worldwide. Early diagnosis and treatment of cancer may curb the growing burden of the disease. Understanding cancer patients' navigation pathways for seeking treatment is important in order to facilitate early diagnosis and treatment. With this background we conducted a hospital-based cross-sectional study comprising 68 randomly selected cancer inpatients in a tertiary cancer specialty hospital in Odisha, India, to explore the treatment-seeking pathways of the cancer patients and the barriers and enablers in seeking treatment. Financial constraint is one of the major reasons for the delay in accessing treatment, even when patients are suspected of or diagnosed with cancer. Low awareness of the presenting signs and symptoms of cancer and limited knowledge of the availability of cancer diagnosis and treatment facilities are major factors contributing to delay. Family and friends' support is found to be the major enabling factor toward seeking treatment. Generation of awareness of cancer among the general population and primary-care practitioners - including those in alternative systems of medicine - is important. Information on diagnostic and treatment services appears to be a felt need. PMID- 24211154 TI - Efficacy of a static progressive stretch device as an adjunct to physical therapy in treating adhesive capsulitis of the shoulder: a prospective, randomised study. AB - BACKGROUND: Stress relaxation and static progressive stretch are techniques used for non-surgical restoration of shoulder range of motion for patients with adhesive capsulitis. OBJECTIVES: To compare a static progressive stretch device plus traditional therapy with traditional therapy alone for the treatment of adhesive capsulitis of the shoulder. DESIGN: Prospective, randomised controlled trial. PARTICIPANTS: Sixty patients with adhesive capsulitis of the shoulder were assigned at random to an experimental group or a control group. INTERVENTIONS: Both groups received three traditional therapy sessions per week for 4 weeks. In addition, the experimental group used a static progressive stretch device for 4 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was shoulder range of motion (active and passive shoulder abduction, and passive shoulder external rotation). The secondary outcome measures were function [measured by the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire] and pain [measured using a visual analogue scale (VAS)]. RESULTS: At baseline, there were no differences between the two groups. However, after the intervention, there were significant (P<0.05) differences between the groups for all outcome parameters: 0.3 for mean VAS scores [95% confidence interval (CI) -0.6 to 1.1], 10.1 for DASH scores (95% CI -21.0 to 0.9), 21.2 degrees for shoulder passive external rotation (95% CI 16.8 to 25.7), 26.4 degrees for shoulder passive abduction (95% CI 17.4 to 35.3), and 27.7 degrees for shoulder active abduction (95% CI 20.3 to 35.0). At 12-month follow-up, the differences between the groups were maintained and even increased for mean shoulder range of motion, VAS scores and DASH scores, with significant differences (P<0.001) between the groups: -2.0 for VAS scores (95% CI -2.9 to -1.2), -53.8 for DASH scores (95% CI -64.7 to 42.9), 47.9 degrees for shoulder passive external rotation (95% CI 43.5 to 52.3), 44.9 degrees for shoulder passive abduction (95% CI 36.0 to 53.8), and 94.3 degrees for shoulder active abduction (95% CI 87.0 to 101.7). CONCLUSION: Use of a static progressive stretch device in combination with traditional therapy appears to have beneficial long-term effects on shoulder range of motion, pain and functional outcomes in patients with adhesive capsulitis of the shoulder. At 12-month follow-up, the experimental group had continued to improve, while the control group had relapsed. PMID- 24211155 TI - The entry of Colombian-sourced heroin into the US market: the relationship between competition, price, and purity. AB - There have been large structural changes in the US heroin market over the past 20 years. Colombian-sourced heroin entered the market in the mid-1990s, followed by a large fall in the price per pure gram and the exit of Asian heroin. By the 2000s, Colombian-sourced heroin had become a monopoly on the east coast and Mexican-sourced heroin a monopoly on the west coast with competition between the two in the middle. We estimate the relationship between these changes in competitive market structure on retail-level heroin price and purity. We find that the entry of Colombian-sourced heroin is associated with less competition and a lower price per pure gram of heroin at the national level. However, there is wide variation in changes in market concentration across the US. Controlling for the national fall in the heroin price, more competition in a region or city is associated with a lower price per pure gram. PMID- 24211157 TI - The missing 'P' in pain management: how the current opioid epidemic highlights the need for psychiatric services in chronic pain care. AB - OBJECTIVE: The prevalence of opioid therapy for chronic noncancer pain has increased dramatically in recent years, with a parallel increase in opioid abuse, misuse and deaths from accidental overdose. We review epidemiological and clinical data that point to the important roles psychiatric disorders have in the use and abuse of opioids in patients with chronic pain. METHOD: We conducted literature searches on the PubMed with the key phrases "chronic pain" and "opioid therapy" and selected those articles on the epidemiology of comorbidity between chronic pain and psychiatric disorders, the trends in long-term opioid therapy and the clinical trials that involved using opioid therapy for chronic pain or for mental health disorders. We then thoroughly reviewed the bibliography of all relevant articles to identify additional papers to be included in the present review. RESULTS: Chronic pain is highly comorbid with common psychiatric disorders. Patients with mental health and substance abuse disorders are more likely to receive long-term opioid therapy for chronic pain and more likely to have adverse outcomes from this therapy. Although opioids may exert brief antidepressant and anxiolytic effects in some patients with depression or anxiety, there is scant evidence for long-term benefit from opioid treatment of psychiatric disorders. CONCLUSIONS: Opioids may be used in current clinical practice as the de facto and only psychiatric treatment for patients with chronic pain, despite little evidence for sustained benefit. The opioid epidemic thus reflects a serious unmet need for better recognition and treatment of common mental health problems in patients with chronic pain. Psychiatry is the missing P in chronic pain care. PMID- 24211158 TI - The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis: a comparative study. AB - OBJECTIVE: The aim of this study was to examine the current prevalence of major depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis (HT) and euthyroid goiter. METHOD: The study sample was formed by consecutive 51 and 45 patients who were admitted to the endocrinology outpatient clinic and diagnosed with euthyroid HT and endemic/nonendemic goiter, respectively, and 68 healthy controls. Current diagnoses of psychiatric disorders were determined using the Structured Clinical Interview for DSM-IV. Beck Depression Inventory and Beck Anxiety Inventory were applied to the participants. RESULTS: There was a statistically significant difference among the three groups in terms of major depression (P=.001), any mood or anxiety disorder (P=.000), any depressive disorder (P=.020), any anxiety disorder (P=.016) and obsessive compulsive disorder (OCD) (P=.013). In the HT group, the prevalence of depression (P=.000), OCD (P=.005) and panic disorder (P=.041) was significantly higher than that in the control group. In the goiter group, depression (P=.006), any depressive disorder (P=.03), and any mood or anxiety disorder (P=.000) were significantly common in comparison to the control group. No significant difference was found between the HT and goiter groups. CONCLUSIONS: Euthyroid HT and euthyroid goiter increase predisposition to major depression and anxiety disorders, and thyroid autoimmunity and other thyroid pathologies should be investigated in euthyroid patients with chronic and treatment-resistant complaints. PMID- 24211156 TI - Holding back sharing concerns, dispositional emotional expressivity, perceived unsupportive responses and distress among women newly diagnosed with gynecological cancers. AB - OBJECTIVE: Little attention has been paid to the role of holding back sharing concerns in the psychological adaptation of women newly diagnosed with gynecological cancers. The goal of the present study was to evaluate the role of holding back concerns in psychosocial adjustment and quality of life, as well as a possible moderating role for emotional expressivity and perceived unsupportive responses from family and friends. METHOD: Two hundred forty-four women diagnosed with gynecological cancer in the past 8 months completed measures of holding back, dispositional emotional expressivity, perceived unsupportive responses from family and friends, cancer-specific distress, depressive symptoms and quality of life. RESULTS: Emotional expressivity moderated the association between holding back and cancer-specific distress and quality of life, but not depressive symptoms. Greater holding back was more strongly associated with higher levels of cancer-related distress among women who were more emotionally expressive than among women who were less expressive. Perceived unsupportive responses did not moderate the associations between holding back and psychosocial outcomes. CONCLUSION: Holding back sharing concerns was more common in this patient population than other cancer populations. Dispositional expressivity played a role in how harmful holding back concerns was for women, while unsupportive responses from family and friends did not. PMID- 24211159 TI - Inhalation and dietary exposure to Dechlorane Plus and polybrominated diphenyl ethers in Osaka, Japan. AB - This study estimated daily exposure to Dechlorane Plus (DP) and polybrominated diphenyl ethers (PBDE) via inhalation and diet. Samples of atmospheric particles and food (obtained by market basket method) from Osaka, Japan were analyzed for DP (syn-, anti-) and PBDE using gas chromatography-mass spectrometry. DP was detected in both atmospheric particles and food samples. Among the atmospheric particles, DP was detected in all samples. SigmaDP concentration was 7.1-15.4 pg m(-3) and anti-DP was the dominant residue among DP isomers. PBDE was also detected in all the atmospheric particles. SigmaPBDE concentration was 9.9-23.3 pg m(-3). In the market basket study, DP was detected in Groups SH (sugar and confectionary), V (legumes and their products), X (fish, shellfish, and their products), and XI (meat and eggs) at concentrations of 3.3, 2.8, 1.9, and 1.5 pg g(-1) wet wt, respectively. PBDE was detected in Groups SH, IV (oils and fats), V, X, XI, and XSH (seasonings and other processed foods) at concentrations of 153, 79.1, 74.6, 308, 94.8, and 186 pg g(-1) wet wt, respectively. The daily intake of SigmaDP (750 pg day(-1)) via inhalation and diet was approximately one percent of that for SigmaPBDE (62 ng day(-1)). PMID- 24211160 TI - Polycyclic aromatic hydrocarbons in oysters and sediments from the Yatsushiro Sea, Japan: comparison of potential risks among PAHs, dioxins and dioxin-like compounds in benthic organisms. AB - Polycyclic aromatic hydrocarbons (PAHs) were analyzed in oysters collected from 18 stations in the Yatsushiro Sea, western Japan. PAHs were detected in all samples analyzed, and the highest concentration (mean 230 ng/g wet weight) was found in oysters from Tanoura Bay. The high molecular weight PAHs to low molecular weight PAHs ratios in oysters from Tanoura Bay were higher than at other stations. Sediment samples collected from 42 stations in Tanoura Bay were analyzed for PAHs to understand their concentrations and distribution. Higher concentrations were found in sediment samples at two stations in the southern inner bay (mean 30,200 ng/g dry weight), which were approximately two orders of magnitude higher than at a reference site. These observations strongly suggest severe contamination and significant sources of PAHs in Tanoura Bay. Dioxins and dioxin-like compounds (PCDFs, and non- and mono-ortho coplanar PCBs) were analyzed in sediments from eight stations in Tanoura Bay. The concentrations were comparable to, or lower than, at the reference sites, suggesting that there are no specific sources of these compounds in this bay. PAH, dioxins and dioxin-like compounds DR-CALUX relative potencies (REP) were applied to the sediment concentrations to evaluate the potential for toxicological effects on benthic organisms. PAHs made the highest contribution to the total REP concentration, supplying 99% of the total REP, followed by PCDDs (0.18%), PCDFs (0.04%), and PCBs (<0.001%). In this area, PAHs appear to be the most important Ah receptor binding chemicals for potential toxicity to benthic species. PMID- 24211161 TI - Impact of the IASLC/ATS/ERS classification in pN0 pulmonary adenocarcinomas: a study with radiological-pathological comparisons and survival analyses. AB - The aim of this study was: (1) to compare the new pathological findings as detected by the IASLC/ATS/ERS classification with the traditional radiological features in pulmonary pN0 adenocarcinomas, (2) to evaluate their prognostic significance on overall survival (OS). A total of 42 surgically resected pN0 pulmonary adenocarcinomas were analyzed. On CT scans, the following radiological data were recorded: sphericity, predominant margins, cavitation and bronchogram, attenuation and percentage of ground glass opacity (GGO). On pathological examination, tumors were categorized according to the IASLC/ATS/ERS classification; Sica score and grade, pathological stage, tumor major axis, pleural invasion, vascular and lymphatic invasion, peritumoral lymphoid infiltration, and cytological features were also determined. Clinical follow up was available in 37 cases (range 1-117 months). Radiologically, 31 solid and 11 semisolid tumors were found. Morphologically, 2 minimally invasive and 40 invasive adenocarcinomas were diagnosed. In radiological-pathological comparisons, (1) the acinar pattern was higher in tumors with solid attenuation and low GGO (p=0.018); (2) the lepidic pattern was more elevated in tumors with high GGO (p=0.012). In multivariate survival analyses with stage, predominant margins on CT scans (p=0.036) and Sica score (p=0.028) significantly affected OS. This study confirms the validity of the new classification of pulmonary adenocarcinomas in radiological-pathological comparisons and underlines the importance of both radiological and pathological findings in correctly identifying their prognostic features. PMID- 24211162 TI - Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice. AB - Endothelial lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related cardiovascular disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice. PMID- 24211164 TI - Dasatinib and docetaxel in advanced prostate cancer. PMID- 24211163 TI - Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. AB - BACKGROUND: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 MUmol/mol creatinine vs >=60 MUmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. FINDINGS: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19.0 months (IQR 11.2-25.1) and 914 patients had died. Median overall survival was 21.5 months (95% CI 20.3-22.8) in the dasatinib group and 21.2 months (20.0-23.4) in the placebo group (stratified hazard ratio [HR] 0.99, 95.5% CI 0.87-1.13; p=0.90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). INTERPRETATION: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. FUNDING: Bristol-Myers Squibb. PMID- 24211165 TI - Rectal injury following delivery as a possible consequence of endometriosis of the rectovaginal septum. PMID- 24211166 TI - Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England. AB - BACKGROUND: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. METHODS: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. RESULTS: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. CONCLUSIONS: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types. PMID- 24211167 TI - Evaluating the efficacy of rBmHATalphac as a multivalent vaccine against lymphatic filariasis in experimental animals and optimizing the adjuvant formulation. AB - Developing an effective vaccine against lymphatic filariasis will complement the WHO's effort to eradicate the infection from endemic areas. Currently 83 different countries are endemic for this infection and over 1 billion people are at risk. An effective vaccine coupled with mass drug administration will reduce the morbidity and social stigma associated with this gruesome disease. Several potential vaccine candidates that can confer partial protection in experimental animals have been reported from different laboratories. However, no licensed vaccines are currently available for this disease. Among the several vaccine antigens identified from our laboratory, three most promising antigens; rBmHSPalphac (alpha crystalline domain and c-terminal extension of Heat Shock Protein 12.6), rBmALT-2 (Abundant larval transcript) and rBmTSP LEL (Tetraspanin large extracellular loop) was further developed as a recombinant fusion protein vaccine (rBmHATalphac). In a mouse model this fusion protein vaccine gave close to 68% protection following a challenge infection. To improve the vaccine efficiency of rBmHATalphac, in this study we evaluated various preparations of alum (AL007, AL019, Alhydrogel and Imject(r) Alum) as adjuvants. Our results show that mice immunized with rBmHATalphac formulated in AL007 (alum from IDRI) and/or AL019 (alum plus TLR-4 agonist from IDRI) gave the highest IgG antibody titer compared to other groups. Subsequent in vivo challenge experiments confirmed that >95% protection can be achieved when AL007 or AL019 was used as the adjuvant. However, when Imject(r) Alum or alhydrogel was used as the adjuvant only 76% and 72% protection respectively could be achieved. These results show that AL007 or AL019 (IDRI) is an excellent choice of adjuvant for the rBmHATalphac vaccine against B. malayi L3 in mice. PMID- 24211168 TI - Computational designing of a poly-epitope fecundity vaccine for multiple species of livestock. AB - Inhibin and follistatin are known to reduce fecundity by inhibiting the actions of activin and FSH. Thus, the immunoneutralization of these hormones is a rational proposal for augmenting reproductive performance. The present study describes a comprehensive computational methodology comprising of a consensus approach of several B- and Th-cell epitope prediction tools for the identification of epitopic regions within the structure of these hormones that can be incorporated into a poly-epitope fecundity vaccine. The proposed peptide (RGD-WSPAALRLLQRPPEEPA-KK-YSFPISSILE) should be effective in multiple animal species, generating good immunological memory. PMID- 24211170 TI - Human papillomavirus vaccination and Pap testing profile in Manitoba, Canada. AB - BACKGROUND: Females who receive the human papillomavirus (HPV) vaccine may believe they are protected from developing cervical cancer and no longer require screening. Concern has also been expressed that vaccinated females are those that would be screened regularly. This study assesses the Pap testing behavior of vaccinated and non-vaccinated females. METHODS: For this population-based retrospective cohort study, vaccination and screening registries were linked for 3540 vaccinated females aged 15 years and over and 9592 matched non-vaccinated females. Conditional logistic regression, the Kaplan-Meier method and Cox regression were used to examine the association between vaccination and Pap testing. RESULTS: Vaccinated females were more likely to have had a Pap test within the year prior to the index date than non-vaccinated females (15-19 years old: OR=1.38, 95% CI 1.20-1.59; 20+ years old: OR=2.34, 95% CI 1.98-2.76). In the three-year period after the index date, vaccinated females had a significantly higher cumulative probability of having a Pap test (83.3%) than non-vaccinated females (66.1%). Females who had a Pap test within three years prior to the index date were more likely to have a Pap test after the index date (vaccinated: HR=5.03, 95% CI 4.65-5.45; non-vaccinated HR=3.97, 95% CI 3.70-4.24). Being vaccinated had a significant effect on Pap testing (15-19 years old: HR=1.54, 95% CI 1.39-1.69; 20+ years old: HR=1.87, 95% CI 1.52-2.31). 80.1% of vaccinated females who had a Pap test prior to the index date also had one subsequent to it, compared to 70.1% for non-vaccinated females. 41.1% of females had not been vaccinated nor had a Pap test. CONCLUSION: The majority of vaccinated females continue to participate in screening, and do so at a higher rate than non vaccinated females. Renewed efforts need to be made to include the large proportion of non-vaccinated, non-screened females in vaccination and/or screening. PMID- 24211169 TI - A modified surface killing assay (MSKA) as a functional in vitro assay for identifying protective antibodies against pneumococcal surface protein A (PspA). AB - Streptococcus pneumoniae causes otitis media, meningitis and pneumonia in patients worldwide; predominantly affecting young children, the elderly, and the immune compromised. Current vaccines against invasive pneumococcal disease are based on the polysaccharide capsules of the most clinically relevant serotypes. Due to serotype replacement, non-vaccine serotypes of S. pneumoniae have become more clinically relevant and as a result pneumococcal vaccines are becoming increasingly complex. These events emphasize the need to evaluate the potential for pneumococcal cross-reactive proteins to contribute to future vaccines. Antibody elicited by the immunization of humans with pneumococcal surface protein A (PspA) can passively protect mice from infection. However, robust in vitro functional assays for antibody to PspA are not available to predict the protective capacity of immune serum. For polysaccharide based vaccines, a standardized opsonophagocytosis killing assay (OPKA) is used. Antibody to PspA, however, does not work well in the standard OPKA. The present studies take advantage of past observations that phagocytosis is more efficient on tissue surfaces than in solution. In a modified surface killing assay (MSKA), monoclonal antibody to PspA, in the presence of complement, opsonized pneumococci for killing by phagocytes on an agar surface. Five monoclonal antibodies to PspA were tested; three demonstrated increased amounts of killing compared to the diluent control and protected mice by passive protection against type 3 pneumococci. The two antibodies that were not functional in the MSKA also failed to protect mice. Thus, an MSKA might be useful as a functional assay for immunity to PspA. PMID- 24211171 TI - [Prevalence and functions of self-injurious thoughts and behaviors in a sample of Spanish adolescents assessed in mental health outpatient departments]. AB - INTRODUCTION: Suicidal and self-injurious behaviors in adolescents are a major public health concern. However, the prevalence of self-injurious thoughts and behaviors in Spanish outpatient adolescents is unknown. METHODS: A total of 267 adolescents between 11 and 18 year old were recruited from the Child and Adolescent Outpatient Psychiatric Services, Jimenez Diaz Foundation (Madrid, Spain) from November 1st 2011 to October 31st 2012. All participants were administered the Spanish version of the Self-Injurious Thoughts and Behaviors Inventory, which is a structured interview that assesses the presence, frequency, and characteristics of suicidal ideation, suicide plans, suicide gestures, suicide attempts, and non-suicidal self-injury. RESULTS: One-fifth (20.6%) of adolescents reported having had suicidal ideation at least once during their lifetime. Similarly, 2.2% reported suicide plans, 9.4% reported suicide gesture, 4.5% attempted suicide, and 21.7% reported non-suicidal self-injury, at least once during their lifetime. Of the whole sample, 47.6% of adolescents reported at least one of the studied thoughts or behaviors in their lifetime. Among them, 47.2% reported 2 or more of these thoughts or behaviors. Regarding the reported function of each type of thoughts and behaviors examined, most were performed for emotional regulation purposes, except in the case of suicide gestures (performed for the purposes of social reinforcement). CONCLUSIONS: The high prevalence and high comorbidity of self-injurious thoughts and behaviors, together with the known risk of transition among them, underline the need of a systematic and routine assessment of these thoughts and behaviors in adolescents assessed in mental health departments. PMID- 24211172 TI - Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study. AB - OBJECTIVE: To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. DESIGN: Unmasked, controlled, randomized clinical trial. PARTICIPANTS: One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers. INTERVENTIONS: In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination. MAIN OUTCOME MEASURES: The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols. RESULTS: Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis achieved statistical significance, with the participants in the device arm demonstrating a smaller decline in visual acuity with fewer letters lost from baseline to CNV detection (median, -4 letters; interquartile range [IQR], -11.0 to -1.0 letters) compared with standard care (median, -9 letters; IQR, -14.0 to -4.0 letters; P = 0.021), resulting in better visual acuity at CNV detection in the device arm. The Data and Safety Monitoring Committee recommended early study termination for efficacy. CONCLUSIONS: Persons at high risk for CNV developing benefit from the home monitoring strategy for earlier detection of CNV development, which increases the likelihood of better visual acuity results after intravitreal anti-VEGF therapy. PMID- 24211173 TI - Trans- and cis-stilbene isolated in cryogenic argon and xenon matrices. AB - Monomers of trans- (TS) and cis-stilbene (CS) were isolated in cryogenic argon and xenon matrices, and their infrared (IR) spectra were fully assigned and interpreted. The interpretation of the vibrational spectra received support from theoretical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level of theory. In situ broadband UV irradiation of the matrix-isolated CS led to its isomerization to TS, which appeared in the photolysed matrices in both non-planar and planar configurations. The non-planar species was found to convert into the more stable planar form upon subsequent annealing of the matrices at higher temperature. TS was found to be photostable under the used experimental conditions. The structure of the non-planar TS form was assigned based on the comparison of its observed IR spectrum with those theoretically predicted for different conformations of TS. Chemometrics was used to make this assignment. Additional reasoning on the structure of the studied stilbenes is presented taking as basis results of the Natural Bond Orbital analysis. PMID- 24211174 TI - Osteochondral autograft transplantation in the elbow. PMID- 24211175 TI - Stability of acute dorsal fracture dislocations of the proximal interphalangeal joint: a biomechanical study. AB - PURPOSE: We performed a cadaveric biomechanical study to characterize proximal interphalangeal joint stability after an injury to different amounts of the volar articular base of the middle phalanx (intact, 20%, 40%, 60%, and 80% volar defects). METHODS: Eighteen digits on 6 hands were tested through full proximal interphalangeal joint range of motion using computer-controlled flexion and extension via the digital tendons. We collected proximal interphalangeal joint kinematic cine data in a true lateral projection with mini-fluoroscopy. We measured the amount of dorsal middle phalanx translation in full proximal interphalangeal joint extension. As we cycled the joint from full flexion into extension, we recorded the angle at which subluxation occurred. RESULTS: No specimens with 20% volar bony defect subluxated. All specimens in the 60% and 80% groups subluxated at an average flexion angle of 67 degrees (range, 10 degrees to 90 degrees ) in the 60% group and at all degrees of flexion in the 80% group. In the 40% group, 28% of specimens demonstrated subluxation at an average flexion angle of 14 degrees (range, 4 degrees to 40 degrees ). Mean dorsal translation of the middle phalanx in relation to the proximal phalanx at full digital extension was 0.2 mm in the 20% group, 0.8 mm in the 40% group, 3.2 mm in the 60% group, and 3.1 mm in the 80% group. CONCLUSIONS: Simulated volar articular bony defects of 20% were stable, whereas those with 60% and 80% defects were unstable during digital motion. Stability in the 40% group was variable and appeared to be the threshold for stability. CLINICAL RELEVANCE: Knowledge of the typical amount of middle phalanx defect and degree of proximal interphalangeal joint extension that can lead to joint instability may improve management of mechanically important proximal interphalangeal joint fracture dislocations. PMID- 24211176 TI - Raynaud disease. PMID- 24211177 TI - Pediatric replantation. PMID- 24211178 TI - Facial emotion recognition and its correlation with executive functions in bipolar I patients and healthy controls. AB - INTRODUCTION: The ability to recognize facial emotions is altered in patients with Bipolar Disorder (BD) during mood episodes and even in euthymia, while cognitive functioning is similarly impaired. This recognition is considered a fundamental skill for successful social interaction. However, it is unclear whether the ability to recognize facial emotions is correlated with the cognitive deficits observed in BD. OBJECTIVE: The objective of this study was to evaluate Facial Emotion Recognition (FER) and its correlation with executive function (EF) in BD I patients during mania, depression and euthymia compared to healthy controls. MATERIAL AND METHODS: A total of 110 patients with BD I, 18-40 years old were included (41 in manic episode; 31 in depressive episode and 38 euthymic). Patients were assessed for FER and EF (Wisconsin card sorting test - WCST), along with 96 healthy volunteers (18-40 years old) recruited from the University of Sao Paulo. RESULTS: The results showed that BD I patients had lower FER performance compared to controls on fear subtests, happiness, the surprise test, and FER total scores. Moreover, BD I manic patients showed poorer performance for EF compared to controls. Six out of the seven variables of the WCST correlated with FER in both healthy controls and BD euthymic subjects but not in BD patients during mood episodes. CONCLUSION: Cognitive deficits and difficulties recognizing facial emotions are present in all mood episodes in BD I patients, even during remission. Although FER is not considered a cognitive domain, these results suggest that, along with EF, it has a complementary function. Hence, further studies should investigate this issue in larger samples and verify whether these similarities also occur at a neurobiological level. PMID- 24211179 TI - Biological sulfate removal from construction and demolition debris leachate: effect of bioreactor configuration. AB - Due to the contamination of construction and demolition debris (CDD) by gypsum drywall, especially, its sand fraction (CDD sand, CDDS), the sulfate content in CDDS exceeds the posed limit of the maximum amount of sulfate present in building sand (1.73 g sulfate per kg of sand for the Netherlands). Therefore, the CDDS cannot be reused for construction. The CDDS has to be washed in order to remove most of the impurities and to obtain the right sulfate content, thus generating a leachate, containing high sulfate and calcium concentrations. This study aimed at developing a biological sulfate reduction system for CDDS leachate treatment and compared three different reactor configurations for the sulfate reduction step: the upflow anaerobic sludge blanket (UASB) reactor, inverse fluidized bed (IFB) reactor and gas lift anaerobic membrane bioreactor (GL-AnMBR). This investigation demonstrated that all three systems can be applied for the treatment of CDDS leachate. The highest sulfate removal efficiency of 75-85% was achieved at a hydraulic retention time (HRT) of 15.5h. A high calcium concentration up to 1,000 mg L(-1) did not give any adverse effect on the sulfate removal efficiency of the IFB and GL-AnMBR systems. PMID- 24211180 TI - Evaluation of the phototransformation of the antiviral zanamivir in surface waters through identification of transformation products. AB - The antiviral zanamivir has been recently reported to occur in surface waters where its presence may lead to the selection of resistant strains of virus in aquatic fauna. In order to evaluate the fate of zanamivir in surface waters, its susceptibility to phototransformation was evaluated using simulated and natural sunlight. Upon exposure of aqueous solutions (20MUgL(-1)) to simulated sunlight, zanamivir in surface water degraded at t1/23.6h. Under natural sunlight in surface water about 30% of the initial concentration of the antiviral disappeared within 18 days. The experiments with surface water showed similar effect as humic acid addition with expected decreasing effect on degradation while nitrate addition showed increasing effect. In the experiments with artificial sunlight at high concentrations of zanamivir, four photoproducts were tentatively identified by hydrophilic interaction chromatography-LTQ-Orbitrap-MS, showing [M+H](+) ions at m/z 112 (TP111), m/z 275 (TP274), m/z 323 (TP322), and m/z 333 (TP332). However at 20MUgL(-1) only the formation of the recalcitrant TP111 was observed. The proposed structures were rationalized by photolysis mechanisms. Photoproduct TP111 was confirmed with a commercially available standard (isocytosine). In summary, the findings suggest that the photodegradation of zanamivir in surface waters proceeds with slow kinetics. PMID- 24211181 TI - Blood disorders after kidney transplantation. AB - Post transplant anemia (PTA) is a common issue in kidney transplant recipients. Most importantly it is associated with an impaired allograft function. Other important factors associated with PTA are immunosuppressive drugs (MPA, AZA and SRL), iron deficiency, infections (Parvo B19), older donor age, rejection episodes, an increased inflammatory state, and erythropoietin hyporesponsiveness. As there are no adequately powered RCTs in the kidney transplant population on anemia treatment with ESA, we have to rely on what we know from the large RCTs in the CKD population. The recently published KDIGO guidelines do not recommend treatment with ESA if Hb is >10 g/dl. Repletion of iron stores is emphasized. Post transplant leukopenia (PTL) and thrombocytopenia (PTT) are frequent complications especially in the first six months after kidney transplantation. Myelosuppression caused by immunosuppressive agents (MPA, AZA, SRL, rATG), antimicrobial drugs (VGCV), and CMV infection is the predominant cause. There are no widely accepted guidelines on treatment strategies, but most often dose reduction or discontinuation of causative medication is done. Most clinicians tend to decrease MPA dose, but this is eventually associated with an increase in acute rejection episodes. VGCV dose reduction (preemptive treatment instead of CMV prophylaxis) may be a successful strategy. In severe cases G-CSF treatment is an important management option and seems to be safe. PMID- 24211182 TI - Gating pluripotency via nuclear pores. AB - In recent years, growing evidence has pointed to the interesting idea that pluripotency might be regulated by a nuclear-pore-coordinated network that controls the level of pluripotency factors in the nucleus. A thorough understanding of this process might improve our comprehension of cell pluripotency and differentiation during embryogenesis, as well as aiding the development of novel models for studying human diseases. PMID- 24211183 TI - Tumor necrosis factor receptor signaling in keratinocytes triggers interleukin-24 dependent psoriasis-like skin inflammation in mice. AB - Psoriasis is a common chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-kappaB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-kappaB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-kappaB, ERK, IL-24, IL 22R1, and STAT3 signaling to disease initiation. PMID- 24211185 TI - The haplosporidian Bonamia exitiosa is present in Australia, but the identity of the parasite described as Bonamia (formerly Mikrocytos) roughleyi is uncertain. AB - Protistan oyster parasites in the genus Bonamia have been observed in recent years infecting new hosts on five continents, with most of these parasites genetically similar to austral species Bonamia exitiosa and Bonamia roughleyi. Identification of the newly observed parasites as one or another of these described species has been complicated by the fact that B. exitiosa and B. roughleyi are phylogenetically indistinguishable at the small-subunit ribosomal DNA (SSU rDNA) level, with samples of B. roughleyi type material no longer available for genetic re-analyses using more informative internal transcribed spacer (ITS) region DNA sequences. To resolve this issue, we evaluated B. roughleyi in field collections of hosts Saccostrea glomerata and Ostrea angasi (as well as Crassostrea gigas) in New South Wales, Australia in 2006 and 2007, and re-analyzed histological samples from the original description of this parasite species using in situ hybridization. Despite (1) reports of the oyster disease putatively caused by B. roughleyi during the time of collections, (2) the observation of gross lesions characteristic of the disease, and (3) the observation of B. roughleyi cells in association with the lesions, we detected a Bonamia sp. by PCR in just 1/42 O. angasi (2.4%), and 1/608 S. glomerata (0.2%), the latter oyster of which is the type host. SSU rDNA sequences of the amplicons were nearly identical to those of B. exitiosa and B. roughleyi, and phylogenetic analysis of ITS region sequences placed them on a B. exitiosa clade. A Haplosporidium sp. sequence similar to that of H. costale was PCR-amplified from nearly half the S. glomerata and O. angasi, but no Haplosporidium sp. was observed histologically. Our inability to identify a Bonamia sp. sequence in association with the B. roughleyi observed histologically suggests that this parasite is not a Bonamia sp. at all, and should be regarded as B. roughleyi nomen dubium. We conclude that the Bonamia sp. that we and other investigators detected in southeastern Australian S. glomerata and O. angasi was B. exitiosa. PMID- 24211184 TI - Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. AB - Upon infection, CD8(+) T cells undergo a stepwise process of early activation, expansion, and differentiation into effector cells. How these phases are transcriptionally regulated is incompletely defined. Here, we report that interferon regulatory factor 4 (IRF4), dispensable for early CD8(+) T cell activation, was vital for sustaining the expansion and effector differentiation of CD8(+) T cells. Mechanistically, IRF4 promoted the expression and function of Blimp1 and T-bet, two transcription factors required for CD8(+) T cell effector differentiation, and simultaneously repressed genes that mediate cell cycle arrest and apoptosis. Selective ablation of Irf4 in peripheral CD8(+) T cells impaired antiviral CD8(+) T cell responses, viral clearance, and CD8(+) T cell mediated host recovery from influenza infection. IRF4 expression was regulated by T cell receptor (TCR) signaling strength via mammalian target of rapamycin (mTOR). Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responses. PMID- 24211186 TI - Advantages of QBI in TBSS analyses. AB - Diffusion-weighted magnetic resonance imaging (DWMRI) is used to study white matter (WM) in normal and clinical populations. In DWMRI studies, diffusion tensor imaging (DTI) models the WM anisotropy with one dominant direction, detecting possible pathway abnormalities only in large and highly coherent fiber tracts. However, more general anisotropy models like Q-ball imaging (QBI) may provide more sensitive WM descriptors in single patients. The present study aimed to compare DTI and QBI models in a group-level population analysis, using Amyotrophic Lateral Sclerosis (ALS) as a pathological case model of WM tract degeneration. DWMRI was performed in 19 ALS patients and 19 age and sex-matched healthy controls. DTI and QBI estimates were compared in whole-brain tract-based spatial statistics (TBSS) and volume of interest (VOI) analyses, and correlated with ALS clinical scores of disability. A significant decrease of the QBI-derived generalized fractional anisotropy (GFA) was observed in both motor and extramotor fibers of ALS patients compared to controls. Homologue DTI-derived FA maps were only partially overlapping with GFA maps. Particularly, the left corticospinal tracts resulted more markedly depicted by the QBI than by the DTI model, with GFA predicting ALS disability better than FA. The present findings demonstrate that QBI model is suitable for studying WM tract degeneration in population-level clinical studies. Particularly, group-level studies of fiber integrity may benefit from QBI when DTI is biased towards low values, such as in cases of fiber degeneration, and in regions with more than one dominant fiber direction. PMID- 24211187 TI - Effects of RF profile on precision of quantitative T2 mapping using dual-echo steady-state acquisition. AB - The dual echo steady-state (DESS) sequence has been shown successful in achieving fast T2 mapping with good precision. Under-estimation of T2, however, becomes increasingly prominent as the flip angle decreases. In 3D DESS imaging, therefore, the derived T2 values would become a function of the slice location in the presence of non-ideal slice profile of the excitation RF pulse. Furthermore, the pattern of slice-dependent variation in T2 estimates is dependent on the RF pulse waveform. Multi-slice 2D DESS imaging provides better inter-slice consistency, but the signal intensity is subject to integrated effects of within slice distribution of the actual flip angle. Consequently, T2 measured using 2D DESS is prone to inaccuracy even at the designated flip angle of 90 degrees . In this study, both phantom and human experiments demonstrate the above phenomena in good agreement with model prediction. PMID- 24211188 TI - Robust GRAPPA reconstruction using sparse multi-kernel learning with least squares support vector regression. AB - Accuracy of interpolation coefficients fitting to the auto-calibrating signal data is crucial for k-space-based parallel reconstruction. Both conventional generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction that utilizes linear interpolation function and nonlinear GRAPPA (NLGRAPPA) reconstruction with polynomial kernel function are sensitive to interpolation window and often cannot consistently produce good results for overall acceleration factors. In this study, sparse multi-kernel learning is conducted within the framework of least squares support vector regression to fit interpolation coefficients as well as to reconstruct images robustly under different subsampling patterns and coil datasets. The kernel combination weights and interpolation coefficients are adaptively determined by efficient semi infinite linear programming techniques. Experimental results on phantom and in vivo data indicate that the proposed method can automatically achieve an optimized compromise between noise suppression and residual artifacts for various sampling schemes. Compared with NLGRAPPA, our method is significantly less sensitive to the interpolation window and kernel parameters. PMID- 24211190 TI - Family-wide expression characterization of Arabidopsis beta-carbonic anhydrase genes using qRT-PCR and Promoter::GUS fusions. AB - Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes found throughout the phylogenetic tree. The beta-class carbonic anhydrases (beta-CAs) are the predominating class of CAs in plants. Growing evidence underscores the importance of beta-CAs in plant immunity and environmental adaptation in addition to their roles in photosynthesis. However, many fundamental problems in Arabidopsis betaCAs expression remain unsolved. Here we examined the transcript abundance of AtbetaCAs in different tissues of Arabidopsis thaliana, and the accumulation of mRNA in response to CO2 and darkness. Histochemical analysis was performed to study the promoter activity of AtbetaCAs during post-germination seedling growth and in mature plants. All six members of the AtbetaCA subfamily showed a response to changed CO2 level and darkness, but each member showed a specific dynamic pattern. Although expression of each AtbetaCA was unique, in general most AtbetaCAs were synchronously expressed in green leaves since 5 days after germination until flowering. AtbetaCA1 and AtbetaCA2 were most highly expressed in leaves but AtbetaCA2 displayed weaker expression in roots. The level of AtbetaCA3 transcripts was highest in flowers, while AtbetaCA5 was most widely expressed and might be involved in more processes than other members. AtbetaCA6 was unique for increased expression in darkness and no expression in either the anther or pistil. The present study provides useful information for further functional investigation. PMID- 24211189 TI - CP12-mediated protection of Calvin-Benson cycle enzymes from oxidative stress. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) are two energy-consuming enzymes of the Calvin-Benson cycle, whose regulation is crucial for the global balance of the photosynthetic process under different environmental conditions. In oxygen phototrophs, GAPDH and PRK regulation involves the redox-sensitive protein CP12. In the dark, oxidized chloroplast thioredoxins trigger the formation of a GAPDH/CP12/PRK complex in which both enzyme activities are down-regulated. In this report, we show that free GAPDH (A4 isoform) and PRK are also inhibited by oxidants like H2O2, GSSG and GSNO. Both in the land plant Arabidopsis thaliana and in the green microalga Chlamydomonas reinhardtii, both enzymes can be glutathionylated as shown by biotinylated-GSSG assay and MALDI-ToF mass spectrometry. CP12 is not glutathionylated but homodisulfides are formed upon oxidant treatments. In Arabidopsis but not in Chlamydomonas, the interaction between oxidized CP12 and GAPDH provides full protection from oxidative damage. In both organisms, preformed GAPDH/CP12/PRK complexes are protected from GSSG or GSNO oxidation, and in Arabidopsis also from H2O2 treatment. Overall, the results suggest that the role of CP12 in oxygen phototrophs needs to be extended beyond light/dark regulation, and include protection of enzymes belonging to Calvin-Benson cycle from oxidative stress. PMID- 24211191 TI - CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features. AB - CARM1 and PRMT1 are 2 Protein Arginine Methyl Transferases (PRMT) dysregulated in cancer. CARM1 function is contradictory and depicted as facilitating proliferation or differentiation. PRMT1 is required for cell proliferation. CARM1 and PRMT1 cooperate for gene regulation. We report that CARM1 and PRMT1 are significantly overexpressed in 60 patients with Non-Small Cell Lung Carcinomas (NSCLC). CARM1 and PRMT1 correlated in healthy but not tumor tissue. Their levels of expression in tumor tissue were proportional to their levels of expression in the counterpart healthy tissue. Only CARM1 expression was found to be correlated with tumor differentiation and neither CARM1 nor PRMT1 expression was correlated with survival. Accordingly, CARM1 and PRMT1 are overexpressed in 2 NSCLC cell lines, A549 and H1299. Targeting PRMT1 with siRNA reduced proliferation, by decreasing cell growth and inhibiting soft agar colony formation, and promoted differentiation, by increasing the epithelial markers cytokeratin 7 and 8 and decreasing Neuromedin B receptor, which binds a mitogenic factor. siCARM1 yielded similar consequences but the conditions with siCARM1 reflected inhibition of both CARM1 and PRMT1. Together these results suggest that CARM1 and PRMT1 are involved in proliferation in lung cancer with no hierarchy of one protein over the other. The fact that CARM1 targeting suppresses PRMT1 in addition to CARM1 reinforces the functional importance of CARM1/PRMT1 interaction. PMID- 24211192 TI - The effect of a telephone follow-up intervention on illness perception and lifestyle after myocardial infarction in China: a randomized controlled trial. AB - BACKGROUND: Lifestyle modification is an integral component of cardiac secondary prevention, while it has been confirmed that myocardial infarction (MI) patients' health-related behaviors are heavily influenced by their illness perception. OBJECTIVES: To evaluate the effect of a telephone follow-up intervention for improving MI patients' illness perception and lifestyle. DESIGN: A randomized controlled trial, longitudinal research design was employed. SETTINGS: Cardiac care units in four major general hospitals in Guangzhou, China. PARTICIPANTS: Inclusion criteria were being diagnosed with an initial acute MI, being able to communicate orally in Mandarin or Cantonese and read in Chinese, and living in Guangzhou. Exclusion criteria were with continuing uncontrolled arrhythmias or heart failure, being illiteracy, or with a history of major psychiatric illness, exercise-induced asthma, uncontrolled diabetes, or evidence of dementia. METHOD: 124 patients admitted with the first acute MI were randomized to receive either routine care or routine care plus a telephone follow-up intervention, which consist of a pre-discharge education and three telephone follow-up instructions. Data were collected before discharge, at the 6th and the 12th week after discharge from hospital, respectively. RESULTS: At the 6th and the 12th week after discharge, patients in the intervention group had significantly positive perceptions about symptoms of MI (mean difference 3.27, 95% confidence interval 2.48-4.07, p<.001; mean difference 2.12, 95% confidence interval 1.34-2.89, p<.001 respectively) and how long their illness would last (mean difference 0.69, 95% confidence interval -0.91 to -0.47, p<.001; mean difference -0.74, 95% confidence interval -0.96 to -0.51, p<.001 respectively) compared with the control group. The intervention group also had more positive beliefs about the controllability (F=4.23, p=.04) and more improved beliefs about the causes of MI than the control group. Moreover, the intervention improved the patients' nutrition (F=5.16, p=.03) and physical activity at the 12-week follow-up (mean difference 0.37, 95% confidence interval 0.17-0.58, p<.001). CONCLUSION: This telephone follow-up intervention can result in improved illness perception and lifestyle after MI. It could be incorporated into current hospital treatment regimens for MI to improve patients' quality of life. PMID- 24211193 TI - New Caledonian lineages of Psychotria (Rubiaceae) reveal different evolutionary histories and the largest documented plant radiation for the archipelago. AB - New Caledonia is a remote archipelago of the South-West Pacific, whose flora is rich, distinctive, and disharmonic. The interest of botanists has long been attracted by the spatio-temporal origin of this flora, but little attention has been paid to the modes of colonization and the diversification processes that have led to the archipelago's modern flora. To date, no explosive plant radiation has yet been highlighted for New Caledonia. A dated phylogenetic framework on the second richest New Caledonian genus--Psychotria s.l. and its allied genera (tribes Psychotrieae and Palicoureeae, Rubiaceae; ca. 85 species)--is provided in this study to explore its patterns of colonization and diversification in the archipelago. This study is based on a comprehensive species sampling, two nuclear and four plastid loci. Results show that New Caledonia was colonized four times by Psychotria and its allied genera during the Neogene long after its mid-Eocene re-emergence from the sea. The Pacific clade of Psychotrieae, one of the largest plant diversifications in the Pacific islands and the Indo-Pacific region, is absent from New Caledonia, possibly due to niche competition. Although the four lineages colonized New Caledonia relatively simultaneously during the Neogene, they express different evolutionary histories, as revealed by unevenness in species richness and net diversification rates. The genus Geophila has not diversified on New Caledonia, as a non-endemic single species has been documented in the archipelago. The genus Margaritopsis had a moderate level of diversification (four species) similar to that on other Pacific islands. The Psychotria clade NC1 appears to be a relictual lineage, which probably underwent a drastic extinction, with a narrow ecological habitat and dispersal limitations. The Psychotria clade NC2 is the largest and youngest New Caledonian plant radiation, and has undergone the fastest recorded diversification of any endemic lineage in the archipelago, and could be the result of a 'non-adaptive radiation', originating from Australian rainforests. PMID- 24211194 TI - Entrance skin dosimetry and size-specific dose estimate from pediatric chest CTA. AB - BACKGROUND: Size-specific dose estimate (SSDE), which corrects CT dose index (CTDI) for body diameter and is a better measure of organ dose than is CTDI, has not yet been validated in vivo. OBJECTIVE: The purpose was to determine the correlation between SSDE and measured breast entrance skin dose (ESD) for pediatric chest CT angiography across a variety of techniques, scanner models, and patient sizes. METHODS: During 42 examinations done on 4 different scanners over 7 years, we measured mid-sternal ESD as an approximation of breast dose with skin dosimeters. We recorded age, weight, effective tube current, kilovoltage potential, console CTDI, and dose-length product, from which we calculated effective dose. We measured effective chest diameter to convert CTDI to SSDE, and we correlated SSDE with measured ESD, using linear regression. We evaluated image quality to answer the clinical question. RESULTS: Patient mean (+/-SD) age was 8.4 +/- 6.1 years (median, 7.9 years; range, 0.02-19.5 years); mean weight was 35 +/- 27 kg (median, 26 kg; range, 3.5-115 kg); effective chest diameter was 20 +/- 7 cm (median, 19 cm; range, 10-35 cm). Mean effective dose was 2.9 +/- 2.8 mSv (median, 2.2 mSv; range, 0.1-14.4 mSv). We observed a linear correlation (R(2) = 0.98, P < .005) between SSDE (mean, 11 +/- 11mGy; median, 7 mGy; range, 0.5-40 mGy) and breast ESD (mean, 12 +/- 11 mGy; median, 7 mGy; range, 0.3-44 mGy). Our doses, which compared favorably with those previously reported, decreased significantly (P < .05) during the course of our study, because of the introduction of automatic exposure control, low kilovoltage, and high pitch techniques. All studies were of diagnostic quality. CONCLUSION: SSDE is a valid dose measure in children undergoing chest CT angiography over a wide range of scanner platforms, techniques, and patient sizes, and it may be used to model breast dose and to document the results of dose reduction strategies. PMID- 24211195 TI - [Diagnostic reference levels in interventional radiology]. AB - This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. PMID- 24211196 TI - [State of the art and future trends in technology for computed tomography dose reduction]. AB - The introduction of helical and multislice acquisitions in CT scanners together with decreased image reconstruction times has had a tremendous impact on radiological practice. Technological developments in the last 10 to 12 years have enabled very high quality images to be obtained in a very short time. Improved image quality has led to an increase in the number of indications for CT. In parallel to this development, radiation exposure in patients has increased considerably. Concern about the potential health risks posed by CT imaging, reflected in diverse initiatives and actions by official organs and scientific societies, has prompted the search for ways to reduce radiation exposure in patients without compromising diagnostic efficacy. To this end, good practice guidelines have been established, special applications have been developed for scanners, and research has been undertaken to optimize the clinical use of CT. Noteworthy technical developments incorporated in scanners include the different modes of X-ray tube current modulation, automatic selection of voltage settings, selective organ protection, adaptive collimation, and iterative reconstruction. The appropriate use of these tools to reduce radiation doses requires thorough knowledge of how they work. PMID- 24211197 TI - Detecting ligand interactions with G protein-coupled receptors in real-time on living cells. AB - G protein-coupled receptors (GPCRs) are a large group of receptors of great biological and clinical relevance. Despite this, the tools for a detailed analysis of ligand-GPCR interactions are limited. The aim of this paper was to demonstrate how ligand binding to GPCRs can be followed in real-time on living cells. This was conducted using two model systems, the radiolabeled porcine peptide YY (pPYY) interacting with transfected human Y2 receptor (hY2R) and the bombesin antagonist RM26 binding to the naturally expressed gastrin-releasing peptide receptor (GRPR). By following the interaction over time, the affinity and kinetic properties such as association and dissociation rate were obtained. Additionally, data were analyzed using the Interaction Map method, which can evaluate a real-time binding curve and present the number of parallel interactions contributing to the curve. It was found that pPYY binds very slowly with an estimated time to equilibrium of approximately 12h. This may be problematic in standard end-point assays where equilibrium is required. The RM26 binding showed signs of heterogeneity, observed as two parallel interactions with unique kinetic properties. In conclusion, measuring binding in real-time using living cells opens up for a better understanding of ligand interactions with GPCRs. PMID- 24211198 TI - Farnesoid X receptor up-regulates expression of lipid transfer inhibitor protein in liver cells and mice. AB - Apolipoprotein F is a component protein mainly secreted by liver and resides on several lipoprotein classes. It can inhibit lipids transfer between different lipoproteins. FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. It modulates bile acids synthesis and lipids metabolism by transcriptional regulation. We aimed to determine whether apoF can be regulated by FXR. The FXR agonist Chenodeoxycholic acid (CDCA) and GW4064 both can activate the expression of apoF in liver cell lines and in C57/BL6 mouse liver. This is dependent on the binding of FXR to the FXR element ER1 (-2904 to 2892 bp) in the apoF gene promoter. Taken together, we have identified apoF as likely another target gene of FXR. PMID- 24211200 TI - Sirt2 suppresses inflammatory responses in collagen-induced arthritis. AB - Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD(+)-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF kappaB) at lysine 310, resulting in reduced expression of NF-kappaB-dependent genes, including interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis. PMID- 24211199 TI - Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. AB - LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. PMID- 24211201 TI - Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha. AB - (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha H16 (RePhaB) is an enzyme that catalyzes the NADPH-dependent reduction of acetoacetyl-CoA, an intermediate of polyhydroxyalkanoates (PHA) synthetic pathways. Polymeric PHA is used to make bioplastics, implant biomaterials, and biofuels. Here, we report the crystal structures of RePhaB apoenzyme and in complex with either NADP(+) or acetoacetyl-CoA, which provide the catalytic mechanism of the protein. RePhaB contains a Rossmann fold and a Clamp domain for binding of NADP(+) and acetoacetyl-CoA, respectively. The NADP(+)-bound form of RePhaB structure reveals that the protein has a unique cofactor binding mode. Interestingly, in the RePhaB structure in complex with acetoacetyl-CoA, the conformation of the Clamp domain, especially the Clamp-lid, undergoes a large structural change about 4.6 A leading to formation of the substrate pocket. These structural observations, along with the biochemical experiments, suggest that movement of the Clamp-lid enables the substrate binding and ensures the acetoacetyl moiety is located near to the nicotinamide ring of NADP(+). PMID- 24211202 TI - miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway. AB - Cardiomyocytes experience a series of complex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role of miR 138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays a protective role in myocardial adaptation to chronic hypoxia, which is mediated mainly by MLK3/JNK/c-jun signaling pathway. PMID- 24211203 TI - Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species. AB - Macrostemonoside A (MSS.A), an active steroidal saponin from Allium macrostemon Bung has been shown to possess anti-coagulation and anti-obesity effects. However, the functional role of MSS.A on tumor growth has not been elucidated. We found that MSS.A significantly inhibited human colorectal cancer cell growth in Caco2 and SW480 cells. Incubation of SW480 cells with MSS.A for 48 h resulted in cell cycle arrest. Moreover, MSS.A dose-dependently induced apoptosis in SW480 cells as shown by increased AnnexinV positively stained cell population, caspase activation, increased pro-apoptotic and reduced anti-apoptotic Bcl-2 family protein levels. Treatment of SW480 cells with MSS.A resulted in increased reactive oxygen species (ROS) generation. However, pre-incubation of SW480 cells with antioxidant N-acetylcysteine (NAC) attenuated the ROS generation and anti colorectal cancer activities of MSS.A. Lastly, intra-peritoneal injections of MSS.A significantly inhibited tumor formation in BALB/c nude mice carcinogenesis xenograft model by reduced tumor volume and tumor weight when treated at dosages of 10, 50 or 100mg/kg daily for 35 days compared with PBS control. Taken together, our results indicate that MSS.A suppressed colorectal cancer growth and induced cell apoptosis by inducing ROS production, and that MSS.A may have therapeutic relevance in the treatment of human colorectal cancer. PMID- 24211204 TI - Coxsackievirus A16 infection triggers apoptosis in RD cells by inducing ER stress. AB - Coxsackievirus A16 (CA16) infection, which is responsible for hand, foot and mouth disease (HFMD), has become a common health problem in Asia due to the prevalence of the virus. Thus, it is important to understand the pathogenesis of CA16 infection. Viruses that induce endoplasmic reticulum (ER) stress are confronted with the unfolded protein response (UPR), which may lead to apoptotic cell death and influence viral replication. In this study, we found that CA16 infection could induce apoptosis and ER stress in RD cells. Interestingly, apoptosis via the activation of caspase-3, -8 and -9 in the extrinsic or intrinsic apoptotic pathways in RD cells was inhibited by 4-phenyl butyric acid (4PBA), a chemical chaperone that reduces ER stress. These results suggest that CA16 infection leads to ER stress, which in turn results in prolonged ER stress induced apoptosis. This study provides a new basis for understanding CA16 infection and host responses. PMID- 24211205 TI - MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3. AB - The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR 124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3'-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC. PMID- 24211206 TI - Discovery of a disused desaturase gene from the pheromone gland of the moth Ascotis selenaria, which secretes an epoxyalkenyl sex pheromone. AB - Female Ascotis selenaria (Geometridae) moths use 3,4-epoxy-(Z,Z)-6,9 nonadecadiene, which is synthesized from linolenic acid, as the main component of their sex pheromone. While the use of dietary linolenic or linoleic fatty acid derivatives as sex pheromone components has been observed in moth species belonging to a few families including Geometridae, the majority of moths use derivatives of a common saturated fatty acid, palmitic acid, as their sex pheromone components. We attempted to gain insight into the differentiation of pheromone biosynthetic pathways in geometrids by analyzing the desaturase genes expressed in the pheromone gland of A. selenaria. We demonstrated that a Delta11 desaturase-like gene (Asdesat1) was specifically expressed in the pheromone gland of A. selenaria in spite of the absence of a desaturation step in the pheromone biosynthetic pathway in this species. Further analysis revealed that the presumed transmembrane domains were degenerated in Asdesat1. Phylogenetic analysis demonstrated that Asdesat1 anciently diverged from the lineage of Delta11 desaturases, which are currently widely used in the biosynthesis of sex pheromones by moths. These results suggest that an ancestral Delta11-desaturase became dysfunctional in A. selenaria after a shift in pheromone biosynthetic pathways. PMID- 24211207 TI - Sclerostin deficient mice rapidly heal bone defects by activating beta-catenin and increasing intramembranous ossification. AB - We investigated the influence of the osteocyte protein, sclerostin, on fracture healing by examining the dynamics and mechanisms of repair of single-cortex, stabilized femoral defects in sclerostin knockout (Sost(-/-); KO) and sclerostin wild-type (Sost(+/+); WT) mice. Fourteen days following generation of bone defects, Sost KO mice had significantly more bone in the healing defect than WT mice. The increase in regenerating bone was due to an increase in the thickness of trabecularized spicules, osteoblast numbers and surfaces within the defect. Enhanced healing of bone defects in Sost KO mice was associated with significantly more activated beta-catenin expression than observed in WT mice. The findings were similar to those observed in Axin2(-/-) mice, in which beta catenin signaling is known to be enhanced to facilitate bone regeneration. Taken together, these data indicate that enhanced beta-catenin signaling is present in Sost(-/-) mice that demonstrate accelerated healing of bone defects, suggesting that modulation of beta-catenin signaling in bone could be used to promote fracture repair. PMID- 24211208 TI - Cholesterol glucosylation is catalyzed by transglucosylation reaction of beta glucosidase 1. AB - Cholesteryl glucoside (beta-ChlGlc), a monoglucosylated derivative of cholesterol, is involved in the regulation of heat shock responses. beta-ChlGlc, which is rapidly induced in response to heat shock, activates heat shock transcription factor 1 (HSF1) leading to the expression of heat shock protein 70 (HSP70) in human fibroblasts. Identification and biochemical characterization of the enzyme responsible for beta-ChlGlc formation is important for a complete understanding of the molecular mechanisms leading to HSP70-induction following heat shock. Recently, we demonstrated that beta-ChlGlc synthesis is not dependent on UDP-Glucose but glucosylceramide (GlcCer) in animal tissue and human fibroblasts. In this study, we examined the possibility of glucocerebrosidase, a GlcCer-degrading glycosidase, acting as beta-ChlGlc-synthesizing enzyme. Overexpression of beta-glucosidase 1 (GBA1, lysosomal acid beta glucocerebrosidase) led to an increase in cholesterol glucosylation activity in human fibroblasts. Using a cell line generated from type 2 Gaucher disease patients with severe defects in GBA1 activity, we found that cholesterol glucosylation activity was very low in the cells and the overexpression of GBA1 rescued the activity. In addition, purified recombinant GBA1 exhibits conduritol B-epoxide-sensitive cholesterol glucosylation activity. The optimum pH and temperature for cholesterol glucosylation by GBA1 were at about 5.3 and 43 degrees C, respectively. Short chain C8:0-GlcCer was the most effective donor for cholesterol glucosylation activity among GlcCer containing saturated fatty acid (C8:0 to C18:0) tested. GlcCer containing mono-unsaturated fatty acid was more preferred substrate for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acid. These results demonstrate, for the first time, a novel function of GBA1 as a beta-ChlGlc-synthesizing enzyme. Therefore, our results also reveal a new pathway for glycolipid metabolism in mammals. PMID- 24211209 TI - SIRT1 suppresses cellular accumulation of beta-TrCP E3 ligase via protein degradation. AB - beta-Transducin repeat-containing protein (beta-TrCP), an E3 ligase, promotes the degradation of substrate proteins in response to various stimuli. Even though several beta-TrCP substrates have been identified to date, limited information of its upstream regulators is available. Here, we showed that SIRT1 suppresses beta TrCP protein synthesis via post-translational degradation. SIRT1 depletion led to a significant increase in the beta-TrCP accumulation without affecting the mRNA level. Consistently, beta-TrCP protein accumulation induced by resveratrol was further enhanced upon SIRT1 depletion. Rescue of SIRT1 reversed the effect of resveratrol, leading to reduced beta-TrCP protein levels. Proteasomal inhibition led to recovery of beta-TrCP in cells with SIRT1 overexpression. Notably, the recovered beta-TrCP colocalized mostly with SIRT1. Thus, SIRT1 acts as a negative regulator of beta-TrCP synthesis via promoting protein degradation. PMID- 24211210 TI - Autocrine galectin-1 promotes collective cell migration of squamous cell carcinoma cells through up-regulation of distinct integrins. AB - We found that high galectin-1 (Gal-1) mRNA levels were associated with invasive squamous cell carcinoma (SCC) cells that expressed Snail, an epithelial-to mesenchymal transition (EMT) regulator. Both Gal-1 overexpression and soluble Gal 1 treatment accelerated invasion and collective cell migration, along with activation of cdc42 and Rac. Soluble Gal-1 activated c-Jun N-terminal kinase to increase expression levels of integrins alpha2 and beta5, which were essential for Gal-1 dependent collective cell migration and invasiveness. Soluble Gal-1 also increased the incidence of EMT in Snail-expressing SCC cells; these were a minor population with an EMT phenotype under growing conditions. Our findings indicate that soluble Gal-1 promotes invasiveness through enhancing collective cell migration and increasing the incidence of EMT. PMID- 24211211 TI - The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast. AB - Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions. PMID- 24211212 TI - AT1 receptor blocker potentiates shear-stress induced nitric oxide production via modulation of eNOS phosphorylation of residues Thr(495) and Ser(1177.). AB - We tested the hypothesis that AT1R blockade modulates the shear stress-induced (SS) synthesis of nitric oxide (NO) in endothelial cells (EC). The AT1R blocker Candesartan in the absence of the ligand angiotensin II (ang II) potentiated SS induced NO synthesis accompanied by increased p-eNOS(Ser1177) and decreased p eNOS(Thr495). Candesartan also inhibited SS-induced ERK activation and increased intracellular calcium transient in a time-dependent manner. To confirm the role of ERK to modulate p-eNOS(Thr495) and calcium to modulate p-eNOS(Ser1177), the MEK inhibitor U0126 and the calcium chelator BAPTA-AM were used, respectively. Pre-treatment of EC with U0126 completed abrogated basal and SS-induced ERK activation, inhibited p-eNOS(Thr495) and increased NO production by SS. On the other hand, pre-treatment of EC with BAPTA-AM decreased the effects of SS alone or in combination with Candesartan to induce p-eNOS(Ser1177) and partially inhibited the effects of Candesartan to potentiate NO release by SS. The AT1R blockers Losartan and Telmisartan were also tested but only Telmisartan potentiated NO synthesis and blocked SS-induced AT1R activation. Altogether, we provide evidence that Candesartan and Telmisartan potentiate SS-induced NO production even in the absence of the ligand ang II. This response requires both the inhibition of eNOS phosphorylation at its inhibitory residue Thr(495) as well as the increase of eNOS phosphorylation at its excitatory residue Ser(1177). In addition, the response is associated with inhibition of SS-induced ERK activation as well as increasing intracellular calcium transient. One may speculate that these yet undescribed events may contribute to the benefits of ARBs in cardiovascular diseases. PMID- 24211213 TI - Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate. AB - Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine 143 was found to be exposed more than 60A(2) to the solvent in F-actin. Because tyrosine-143 flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (Vmax) were estimated by a double reciprocal plot. The Tyr143Trp actin showed the higher affinity (smaller Kapp) than that of the wild-type actin, with the Vmax being almost unchanged. The Kapp and Vmax of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of Kapp was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas (ASA) of the replaced amino acid molecule. Because 1/Kapp reflects the affinity of F-actin for the myosin-ADP-phosphate intermediate (M.ADP.Pi) through the weak binding, these data suggest that the bulkiness or the aromatic nature of the tyrosin-143 is important for the initial binding of the M.ADP.Pi intermediate with F-actin but not for later processes such as the phosphate release. PMID- 24211214 TI - Let's not forget the thinkers. AB - As 'omics' technologies become more accessible, enormous quantities of data are being generated about the genomes, proteomes, metabolomes, etc. of an increasing number of parasites. We therefore need to think very carefully about how these resources will contribute to our basic understanding of parasitism, and beyond the 'knee-jerk' outcomes of new vaccines and therapeutics. The lasting legacy of the 'omics' era may lie in addressing the fundamental biological hypotheses generated by parasitologists 40-50 years ago when direct observational studies were a feature of parasitological research. We illustrate this with reference to the cestode parasite Echinococcus and the far-reaching questions posed by Desmond Smyth. PMID- 24211215 TI - Ways and entanglements of the waste hierarchy. PMID- 24211216 TI - Heterosandwich immunoswab assay for dengue virus Ns1 antigen detection. AB - Dengue and the more severe dengue hemorrhagic fever have been a very critical public health problem globally. Millions of people especially in the tropical areas get infected with dengue. An efficient diagnostic is very important for early screening of dengue infection. In dengue-infected patients, the nonstructural protein NS1 is present on the surface of infected cells and secreted in plasma. The NS1 antigen is an important target for developing a quick diagnostic largely due to its long presence in the blood. We have developed a simple-to-use immunoswab-based diagnostic procedure employing monoclonal antibodies and the second-generation quadromas. The detection limit for NS1 has been established to be in the subnanogram range. The assay is very sensitive, has a visual end point, and also being extremely inexpensive. With this assay, screening time for a dengue-infected person would be very rapid. PMID- 24211217 TI - Panton-Valentine leukocidin (PVL) gene carriage among Staphylococcus aureus strains with SCCmec types I, III, IV, and V recovered from cystic fibrosis pediatric patients in Brazil. AB - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in patients with cystic fibrosis (CF). We report a molecular characterization, antimicrobial resistance, and Panton-Valentine leukocidin (PVL) toxin gene detection of MRSA strains from 28 Brazilian pediatric CF patients (1 strain per patient). A significant proportion (50%) of MRSA SCCmec IV isolates was observed. Nearly half of MRSA strains harboring the PVL genes distributed in all SCCmec types detected. Multilocus sequence typing (MLST) analyses showed majority (57.1%) of the isolates belonged to known epidemic lineages, such as UK/EMRSA-3, Pediatric/USA 800, Southwest Pacific clone, and Brazilian/Hungarian clone. To our knowledge, this is the first Brazilian study of molecular epidemiology based on MLST and SCCmec typing and the first description of PVL genes in MRSA from CF patients. PMID- 24211218 TI - Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: predominance of KPC-2 enzyme. AB - Among 228 carbapenem-nonsusceptible Enterobacteriaceae isolated in China, 65 were carbapenemase-producing Enterobacteriaceae (CPE). Among them, 41, 22, 1, and 1 produced KPC-2, IMP-4, IMP-8, and IMP-1, respectively. KPC-2-producing CPE showed higher resistance than IMP-4-producing ones. Furthermore, the first outbreak of ST11 KPC-2-producing Klebsiella pneumoniae in a Beijing second-degree hospital was identified. PMID- 24211219 TI - Feedback during CPR in younger children: will it help us do the right thing? PMID- 24211220 TI - Association of umbilical cord plasma acid-labile subunit of the insulin-like growth factor ternary complex with anthropometry in term newborns. AB - BACKGROUND: Birth size can affect neonatal morbidity and mortality. The insulin like growth factor (IGF) system is the most important endocrine factor influencing fetal growth. In the circulation, IGFs (mostly IGF-I) are bound to IGF-binding protein 3 (IGFBP-3) and an acid-labile subunit (ALS) to form a ternary complex. The ALS protects IGFs from decay and facilitates their endocrine activity. However, the function of ALS in fetal growth has not yet been fully determined. METHODS: Venous umbilical plasma samples were obtained from 98 term neonates and analyzed using enzyme-linked immunosorbent assays. The ALS, IGF-I, and IGFBP-3 umbilical cord plasma levels were analyzed for their association with anthropometric measurements of the neonates. RESULTS: The ALS, IGF-I, and IGFBP-3 cord plasma levels were positively correlated with birth weight (r = 0.42, p < 0.001; r = 0.43, p < 0.001; and r = 0.27, p < 0.01, respectively) and placental weight (r = 0.37, p < 0.001; r = 0.31, p < 0.01; and r = 0.30, p < 0.01, respectively). In addition, the ALS cord plasma levels were also positively correlated with head circumference (r = 0.29, p < 0.01). Multiple linear regression analyses showed that both ALS and IGF-I cord plasma levels were independent predictive variables for birth weight (p < 0.01 and p < 0.005, respectively). The ALS cord plasma levels were the only independent predictive variables, however, for head circumference and placental weight (p < 0.01 and p < 0.05, respectively). CONCLUSION: The ALS umbilical cord plasma levels are one important factor, in addition to IGF-I, in the IGF system for predicting birth anthropometry, at least for near-term gestation. Our results suggest that the influence of ALS on the IGF system may develop prior to birth and affect fetal growth. PMID- 24211221 TI - Statistical method for prediction of gait kinematics with Gaussian process regression. AB - We propose a novel methodology for predicting human gait pattern kinematics based on a statistical and stochastic approach using a method called Gaussian process regression (GPR). We selected 14 body parameters that significantly affect the gait pattern and 14 joint motions that represent gait kinematics. The body parameter and gait kinematics data were recorded from 113 subjects by anthropometric measurements and a motion capture system. We generated a regression model with GPR for gait pattern prediction and built a stochastic function mapping from body parameters to gait kinematics based on the database and GPR, and validated the model with a cross validation method. The function can not only produce trajectories for the joint motions associated with gait kinematics, but can also estimate the associated uncertainties. Our approach results in a novel, low-cost and subject-specific method for predicting gait kinematics with only the subject's body parameters as the necessary input, and also enables a comprehensive understanding of the correlation and uncertainty between body parameters and gait kinematics. PMID- 24211222 TI - Interictal serum S-100B protein levels in intractable epilepsy: a case-control study. AB - Epilepsy is the most common neurologic disorder of childhood. In approximately 6 14% of all patients with epilepsy, complete seizure control is difficult to achieve with current antiepileptic treatments. Several current studies have shown in both animals and people that the lengthening of epileptic seizures and frequent recurrence increases the likelihood of neuronal damage. S-100B protein is the most analyzed brain derived peripheral biochemical marker in brain damage. This study aimed to evaluate interictal serum S-100B protein levels in children diagnosed with intractable epilepsy. A group of 32 patients with intractable epilepsy and 25 healthy controls were recruited. Serum S-100B protein levels were measured using a commercially available electrochemiluminescence immunoassay (ECLIA kit, as supplied and according to the manufacturer's standards. The serum S-100B protein levels of the patient group in the study were found to be 0.094+/ 0.011 MUm/L, and 0.083+/-0.014 MUm/L in the age-matched control group. The difference between the groups was determined to be statistically significant (P=0.004). In conclusions, it can be said that as the serum S-100B protein levels of the patients with focal epilepsy were high compared to those of the control group, this can be reliable peripheral biomarker for neuronal damage in patients with focal intractable epilepsy. PMID- 24211223 TI - Using fMRI virtual-reality technology to predict driving ability after brain damage: a preliminary report. AB - The cerebellum, which is important for movement control and planning, is often affected by many neurological conditions. Until now there has been limited information regarding how the function of the cerebellum impacts driving ability. This study used fMRI with an integrated virtual reality driving simulator to determine which aspects of driving performance are related to the cerebellum in healthy drivers (Experiment 1). It also investigated drivers with focal cerebellar lesions to identify how damage to this brain region impairs driving abilities. The results showed that cerebellar functioning is responsible for motor-speed coordination and complex temporal-motor integration necessary to execute driving behaviours. As predicted, drivers with cerebellar damage, showed significantly compromised speed control during basic driving conditions, whereas their ability to perform during interactive driving situations was preserved. New insights into neural mechanisms and brain plasticity regarding driving behaviour are discussed. Strategies in assessing and rehabilitating drivers with related neurological conditions are provided. PMID- 24211224 TI - S100B as a glial cell marker in diabetic peripheral neuropathy. AB - Evidence suggests that acute and chronic hyperglycemia can cause oxidative stress in the peripheral nervous system which, in turn, can promote the development of diabetic neuropathy. Recent studies have found increased expression of glial fibrillary acidic protein (GFAP) and S100B, both of which are indicators of glial reactivity, in the neural and retinal tissues of diabetic rats. For the first time in the literature, the serum levels of GFAP and S100B were assessed in patients with diabetes to evaluate the potential of these factors to serve as peripheral glial biomarkers of diabetes and to investigate their relationship to diabetic peripheral neuropathy. This prospective clinical study included 72 patients with type 2 diabetes mellitus and 50 age- and sex-matched control subjects. All diabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy, and nephropathy. Serum samples were analyzed for human GFAP and S100B using a commercially available Enzyme-linked Immuno Sorbent Assay kit. GFAP was not detected in the serum samples of either diabetic or control patients (p>0.05). However, we found a statistically significant decrease in S100B serum levels in patients with diabetes compared with control participants (p<0.001). No associations between serum S100B levels and the presence of diabetic peripheral neuropathy or other microvascular complications were observed (p>0.05). The findings of markedly decreased serum levels of S100B may possibly indicate a neuroprotective effect of S100B, whereas GFAP may be of no diagnostic value in human patients with diabetes. PMID- 24211225 TI - Subepithelial corneal immunoglobulin deposition as a manifestation of multiple myeloma: a case report and literature review. PMID- 24211226 TI - Imported strongyloidiasis in Spain. AB - OBJECTIVES: The objective of this study was to assess the epidemiological, laboratory, and clinical features of imported strongyloidiasis in a tropical medicine referral unit in Madrid, Spain. METHODS: This was a retrospective study based on a review of medical records. A patient was diagnosed with strongyloidiasis when the infection could be detected by conventional stool analysis and/or serology against Strongyloides stercoralis, regardless of the presence of symptoms. RESULTS: One hundred and seventy-eight cases of strongyloidiasis were included in the study. Stool tests were performed in all patients, and serology in 160 patients (89.9%). The diagnosis of strongyloidiasis was based on serology only in four patients; 21 patients only had positive stool tests. A third of the total strongyloidiasis cases in this study were travel related, mainly associated with short trips (<2 months). Only 47.8% of total cases were symptomatic. We found no differences in clinical presentation between immigrants and travelers with strongyloidiasis. CONCLUSIONS: Not only should strongyloidiasis be suspected in symptomatic travelers and immigrants, but it should also be ruled out when elevated IgE levels or eosinophilia are present. Strongyloidiasis can be asymptomatic in HIV patients, but it should be diagnosed and treated before a possible hyperinfection develops. PMID- 24211228 TI - Bilharzia in the Philippines: past, present, and future. AB - Schistosomiasis japonica has a long history in the Philippines. In 1975, 24 endemic provinces were identified in the northern, central, and southern islands of the Philippines. More than five million people were at risk, with approximately one million infected. In 2003, new foci of infection were found in two provinces in the north and central areas. For the past 30 years, human mass drug administration (MDA), utilizing the drug praziquantel, has been the mainstay of control in the country. Recent studies have shown that the schistosomiasis prevalence ranges from 1% to 50% within different endemic zones. Severe end-organ morbidity is still present in many endemic areas, particularly in remote villages with poor treatment coverage. Moreover, subtle morbidities such as growth retardation, malnutrition, anemia, and poor cognitive function in infected children persist. There is now strong evidence that large mammals (e.g. water buffaloes, cattle) contribute significantly to disease transmission, complicating control efforts. Given the zoonotic nature of schistosomiasis in the Philippines, it is evident that the incidence, prevalence, and morbidity of the disease will not be controlled by MDA alone. There is a need for innovative cost-effective strategies to control schistosomiasis in the long term. PMID- 24211227 TI - Mortality indicators in pneumococcal meningitis: therapeutic implications. AB - BACKGROUND: The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS: This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS: Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195 0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS: Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment. PMID- 24211229 TI - Classification of incidence and prevalence of certain sexually transmitted infections by world regions. AB - OBJECTIVES: This study sought to assess if there is a meaningful way in which variations in sexually transmitted infection (STI) prevalence can be classified at the level of world regions. METHODS: Linear regression was performed to assess if the incidence and prevalence of six STIs (HIV, herpes simplex virus type 2, chlamydia, gonorrhea, syphilis, and trichomoniasis) by world region was positively correlated. Partitioning around medoids (PAM) was then used to assess if the regions of the world can be classified according to the incidence and prevalence of these STIs. RESULTS: We found evidence that STI incidence/prevalence varies considerably in different regions around the world. Linear regression revealed that the incidence and prevalence of certain STIs by world region was positively correlated (Pearson's correlation coefficient varied from 0.664 to 0.985). PAM provided support for dividing the world regions into two, three, or four STI incidence/prevalence categories, but it provided most support for the two-category system. In each of these systems the East Asia/Pacific and North Africa/Middle East regions were in the lowest STI category and Sub-Saharan Africa was the only region in the high STI category. CONCLUSIONS: The incidence and prevalence of certain STIs by world region are positively correlated. The world regions can be meaningfully classified according to STI incidence/prevalence. PMID- 24211230 TI - Community-acquired pneumonia and tuberculosis: differential diagnosis and the use of fluoroquinolones. AB - The respiratory fluoroquinolones moxifloxacin, gemifloxacin, and high-dose levofloxacin are recommended in guidelines for effective empirical antimicrobial therapy of community-acquired pneumonia (CAP). The use of these antibiotics for this indication in areas with a high prevalence of tuberculosis (TB) has been questioned due to the perception that they contribute both to delays in the diagnosis of pulmonary TB and to the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis. In this review, we consider some of the important questions regarding the potential use of fluoroquinolones for the treatment of CAP where the burden of TB is high. The evidence suggests that the use of fluoroquinolones as recommended for 5-10 days as empirical treatment for CAP, according to current clinical management guidelines, is appropriate even in TB-endemic regions. It is critical to quickly exclude M. tuberculosis as a cause of CAP using the most rapid relevant diagnostic investigations in the management of all patients with CAP. PMID- 24211231 TI - Treatment experiences of pelvic bone hydatidosis. AB - BACKGROUND: Hydatid diseases of the pelvic bone are rare, generally incurable, and have high rates of recurrence. METHODS: We report nine cases of osseous hydatidosis involving the pelvis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, reconstruction using a pedicle screw-rod system, and hemipelvic replantation after liquid nitrogen devitalization combined with femoral prosthesis replacement. The therapy was completed by medical treatment or radiotherapy. RESULTS: The average follow-up was 7.3 years (range 2-19 years). Whilst five patients were symptom-free at the last follow-up, the remaining patients suffered from hip pain or productive sinuses. CONCLUSIONS: Patients must be treated at the early stages of the disease. Total exeresis and individual reconstruction is necessary when osseous and soft tissue involvement is not extensive. Internal fixation should not be used when surgical eradication is uncertain. PMID- 24211232 TI - Fluorescence in situ hybridization panel for monitoring of minimal residual disease in patients with double minute chromosomes. AB - A double minute chromosome (dmin) is a small fragment of extrachromosomal DNA bearing amplified genes observed in malignancies. We investigated the incidence and characteristics of dmins in hematologic malignancies, and the quantitative changes during the treatment follow-up. Once a dmin was observed in conventional G-banding, it was characterized using fluorescence in situ hybridization (FISH) with the panel of MYC, NMYC, and MLL probes. Quantitative changes of malignant cells were measured using G-banding and FISH during the follow up. Dmins were observed in 1.23% of patients (6/489) at the initial diagnosis including 4 with MYC amplification, 1 with MLL and 1 with NMYC. All 6 had complex karyotypes and showed short overall survival (7.7 months). In follow-up specimens, FISH detected dmins in 11 cases out of which G-banding detected dmins in 9 cases. The number of dmins detected by FISH and G-banding did not correlate well. Amplification of NMYC in dmins is reported for the first time. A FISH panel composed of frequently amplified oncogenes (MYC, NMYC, and MLL) in dmins is useful for characterization of dmins. FISH is a sensitive method in detecting dmins and will be useful in monitoring of the minimal residual disease. PMID- 24211233 TI - Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1beta induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes. AB - OBJECTIVE: Interleukin-1beta (IL-1beta) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212 2 mesylate (WIN-55) may inhibit cartilage degradation. METHODS: Effects of WIN-55 were studied on IL-1beta stimulated production of MMP-3 and -13 and their inhibitors TIMP-1 and -2 in human chondrocytes. Chondrocytes were obtained from articular cartilage of patients undergoing total knee replacement. Chondrocytes were grown in monolayer and 3D alginate bead cultures. Real-time polymerase chain reaction (PCR) was used to determine the gene expression of MMP-3, -13, TIMP-1 and -2 and Enzyme Linked Immunosorbent Assay (ELISA) to measure the amount of MMP 3 and MMP-13 protein released into media. Immunocytochemistry was used to investigate the expression of cannabinoid receptors in chondrocyte cultures. RESULTS: Treatment with WIN-55 alone or in combination with IL-1beta, decreased or abolished MMP-3, -13, TIMP-1 and -2 gene expression in human chondrocyte monolayer and alginate bead cultures in both a concentration and time dependent manner. WIN-55 treatment alone, and in combination with IL-1beta, reduced MMP-3 and -13 protein production by chondrocytes cultured in alginate beads. Immunocytochemistry demonstrated the expression of cannabinoid receptors in chondrocyte cultures. CONCLUSION: Cannabinoid WIN-55 can reduce both basal and IL 1beta stimulated gene and protein expression of MMP-3 and -13. However WIN-55 also decreased basal levels of TIMP-1 and -2 mRNA. These actions of WIN-55 suggest a mechanism by which cannabinoids may act to prevent cartilage breakdown in arthritis. PMID- 24211235 TI - Altered expression of 5-HT1A receptors in adult rats induced by neonatal treatment with clomipramine. AB - Chronic administration of clomipramine (CMI) to neonatal rats produces behaviors that resemble a depressive state in adulthood. Dysfunctions in the activity of the central nervous system's serotonergic function are important in understanding the pathophysiology of depression. The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the long latency of some antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide. In this study, we analyzed the effect of neonatal administration of CMI on the activity of 5-HT1A receptors, both pre- and post-synaptically, by administering an agonist of 5-HT1A receptors, 8-OH-DPAT, and then subjecting the rats to the forced swimming test (FST) a common procedure used to detect signs of depression in rats. Also measured were levels of the mRNA expression of 5-HT1A receptors in the dorsal raphe (DR), the hypothalamus and the hippocampus. Wistar rats were injected twice daily with CMI at doses of 15mgkg( 1) or saline as vehicle (CON) via s.c. from postnatal day 8 for 14days. At 3 4months of age, one set of rats from each group (CON, CMI) was evaluated for the effect of a selective agonist to the 5-HT1A receptor subtype, 8-OH-DPAT, by testing in the FST. Also determined was the participation of the pre- or post synaptic 5-HT1A receptor in the antidepressant-like action of 8-OH-DPAT. This involved administering an inhibitor of tryptophan hydroxylase, parachlorophenylalanine (PCPA), and pretreatment with 8-OH-DPAT before the FST test and to evaluate the rectal temperature and locomotor activity. The expression of the mRNA of the 5-HT1A receptors was examined in the dorsal raphe nucleus, the hypothalamus and the hippocampus using the semi-quantitative RT-PCR method. The results from this study corroborate that neonatal treatment with clomipramine induces a pronounced immobility in the FST when animals reach adulthood, manifested by a significant decrease in swimming behavior, though counts of climbing behavior were not modified. This effect was similar in magnitude when 8-OH-DPAT was administered to CON group. Furthermore, the administration of 8-OH-DPAT induces a significant and similar increase in rectal temperature and locomotor activity in both the CON as in the CMI group. Neonatal treatment with CMI resulted in a significant decrease in the expression of the mRNA of the 5-HT1A receptors in the DR (% more than vehicle) in adulthood. In the case of the postsynaptic receptors located in the hypothalamus and hippocampus, neonatal treatment with CMI induced a significant increase in the mRNA expression of the 5-HT1A receptors. These data suggest that neonatal treatment with CMI induces a downregulation of the mRNA of the 5-HT1A autoreceptors in the DR, and an increment in the expression of the postsynaptic 5-HT1A receptors. The results after the administration of PCPA and 8-OH-DPAT on FST, rectal temperature and locomotor activity for both groups suggest that the function of postsynaptic receptors remains unchanged. All together these data show that the depressive behavior observed in adulthood in this animal model may be associated with long term alterations in the expression of the mRNA of the 5-HT1A receptors. PMID- 24211236 TI - Impaired inhibition after total sleep deprivation using an antisaccade task when controlling for circadian modulation of performance. AB - OBJECTIVE: Sleep deprivation affects several cognitive functions subserved by the prefrontal cortex. Conflicting results have, nonetheless, been reported for inhibitory function, which could be explained by methodological bias. The present study aimed to assess the effects of sleep deprivation on response inhibition using a particularly suitable inhibition test, the antisaccade, while controlling for circadian influences on performance. For this purpose, testing was conducted at: (1) the same time of day in both the control and sleep deprivation conditions; and (2) at a time of day when inhibitory performance has been found not to be at its lowest level. Two other neuropsychological tasks (go no-go and incompatibility) were used for comparison. METHODS: Twelve healthy young participants performed the three tasks in the early afternoon after a normal night and after a total sleep deprivation (TSD) night in a study with a balanced, crossover design. RESULTS: TSD significantly impaired the error rate, the latency, and the intra-individual coefficient of variation of latency in the antisaccade task. None of these parameters were affected in the two neuropsychological tasks. CONCLUSIONS: When circadian modulation of performance is controlled, TSD impairs inhibition assessed by an antisaccade test. This result emphasizes that it is crucial to control for circadian effects when assessing cognitive performance in TSD studies since the time of testing may reveal or mask cognitive and behavioral impairments. The discrepant findings obtained with the go no-go and incompatibility tests are probably explained by the specific task demands and differences in recruitment of prefrontal regions. PMID- 24211234 TI - Structural determinants of unique properties of human IgG4-Fc. AB - Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange, leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcgammaRII and FcgammaRIII, and complement. These properties render IgG4 relatively "non inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35 A, respectively, of human recombinant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote Fab-arm exchange, and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcgammaRII, FcgammaRIII and C1q binding properties of IgG4 compared with IgG1 and -3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate Fab-arm exchange by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions are compatible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen. PMID- 24211238 TI - Intradermal pre-exposure rabies vaccination. Promises and pitfalls. PMID- 24211237 TI - Effect of dopamine D1 and D2 receptor antagonism in the lateral hypothalamus on the expression and acquisition of fructose-conditioned flavor preference in rats. AB - The attraction to sugar-rich foods is influenced by conditioned flavor preferences (CFP) produced by the sweet taste of sugar (flavor-flavor learning) and the sugar's post-oral actions (flavor-nutrient) learning. Brain dopamine (DA) circuits are involved in both types of flavor learning, but to different degrees. This study investigated the role of DA receptors in the lateral hypothalamus (LH) on the flavor-flavor learning produced the sweet taste of fructose. In an acquisition study, food-restricted rats received bilateral LH injections of a DA D1 receptor antagonist (SCH23390), a D2 antagonist (RAC, raclopride) or vehicle prior to 1-bottle training sessions with a flavored 8% fructose+0.2% saccharin solution (CS+/F) and a less-preferred flavored 0.2% saccharin solution (CS-). Drug-free 2-bottle tests were then conducted with the CS+ and CS- flavors presented in saccharin. The fructose-CFP did not differ among groups given vehicle (76%), 12 nmol SCH (78%), 24 nmol (82%) or 24 nmol RAC (90%) during training. In an expression study with rats trained drug-free, LH injections of 12 or 24 nmol SCH or 12-48 nmol RAC prior to 2-bottle tests did not alter CS+ preferences (77-90%) relative to vehicle injection (86%). Only a 48 nmol SCH dose suppressed the CS+ preference (61%). The minimal effect of LH DA receptor antagonism upon fructose flavor-flavor conditioning differs with the ability of LH SCH injections to block the acquisition of glucose flavor-nutrient learning. PMID- 24211239 TI - Travel and non-travel associated rabies post exposure treatment in New South Wales residents, Australia, 2007-2011: a cross-sectional analysis. AB - BACKGROUND: Australian Bat Lyssavirus is endemic in Australian bats. More Australians are travelling to rabies (Lyssavirus 1) endemic countries. The nature and frequency of lyssavirus exposures and characteristics of New South Wales (NSW) residents exposed have not previously been described. METHOD: Access to free rabies post-exposure treatment (PET) can only be arranged through Public Health Units in NSW. Details of people receiving PET after potential exposures to rabies or ABLV from 1 January 2007 to 31 December 2011 were extracted from an NSW Ministry of Health web-based database and analysed to better understand lyssavirus exposure epidemiology. RESULTS: Of 1195 people receiving PET, 415 exposures were in Australia and 780 abroad; 78.3% occurring in Southeast Asia, mainly Indonesia (47.6%) where most were on the island of Bali (95.2%). PET use increased substantially for domestic and international exposures. In Australia, most bat exposures were to members of the public (76.0%), rather than to people who work with bats professionally or as volunteers, with 54.1% due to bat rescue attempts. Injuries abroad were mainly from monkeys (49.4%) and from dogs (35.8%). Only 4.0% of international travellers were vaccinated prior to their exposure. CONCLUSIONS: Increasing rates of PET in travelling and non-travelling Australians emphasise the need for more effective communication about appropriate animal avoidance and the measures required if exposed. Opportunities for increasing pre exposure treatment amongst individuals likely to be exposed should be promoted. PMID- 24211240 TI - Tungiasis - A Janus-faced parasitic skin disease. AB - Tungiasis is a parasitic skin disease caused by the penetration of female sand fleas (Tunga penetrans). It is acquired when people walk barefoot or rest on soil, where sand fleas have completed the off-host cycle. Tungiasis is a classic poverty-associated disease which belongs to the family of neglected tropical diseases (NTD). It has a Janus-face: while in travellers tungiasis usually is a benign self-limiting skin disease, inhabitants of endemic areas suffer from heavy infestations and severe, frequently debilitating and incapacitating morbidity. We describe the epidemiological and clinical characteristics of travel-associated tungiasis and compare these features to the situation in resource-poor communities in South America and sub-Saharan Africa. PMID- 24211241 TI - Imported Armillifer pentastomiasis: report of a symptomatic infection in The Netherlands and mini-review. AB - We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year old female Liberian immigrant to The Netherlands. The patient was referred to the gynecologist because of lower abdominal pain. During laparotomy, multiple adhesions were seen in the lower pelvis and a hydrosalpinx with an encapsulated Armillifer nymph, most likely Armillifer armillatus, was found. Key features of the parasite's cuticle which facilitate the diagnosis of pentastomiasis, are presented. Symptomatic pentastomiasis is uncommon, and most cases are diagnosed incidentally during surgery for other reasons, or at autopsy. With regard to increasing international migration, other imported pentastomiasis cases to Europe and North America are reviewed, and more cases are likely to be seen in the future. PMID- 24211242 TI - Sun and skin - is travel health advice needed? PMID- 24211243 TI - Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression. AB - KIT inhibition with dasatinib represents a promising approach to targeted therapy in t(8;21) acute myeloid leukemia (AML) and clinical trials are currently evaluating its clinical relevance. However, data on continuous long-term dasatinib exposure of AML cells are limited and the potential effects on KIT inhibition and dasatinib sensitivity are unexplored. Treatment-related resistance ultimately limits clinical efficacy of tyrosine kinase inhibitors (TKI), which could similarly apply to dasatinib in t(8;21) AML. In this study, we used the dasatinib-sensitive KIT(mut) t(8;21) AML cell line Kasumi-1 to model, in a confined and controllable way, molecular effects upon continuous dasatinib treatment. Long-term dasatinib exposure at clinically relevant levels resulted in markedly decreased drug-sensitivity of KIT(mut) t(8;21) AML cells. Notably, all dasatinib-resistant clones lacked secondary KIT-mutations. Instead, persistent growth correlated with alterations in KIT expression levels-that is, either KIT overexpression with maintained downstream signaling or KIT downregulation with concomitant activation of alternate pathways. Although KIT overexpression was associated with retained receptor activity and STAT3 activation, KIT downregulation correlated with decreased STAT3 levels and increased ERK signaling. Importantly, brief discontinuation of dasatinib restored dasatinib sensitivity associated with reversal of signaling signatures similar to treatment naive, dasatinib-sensitive cells. The observed desensitization of KIT(mut) t(8;21) AML cells upon continuous dasatinib exposure suggests that therapy related acquisition of resistance could pose significant limitations on therapeutic efficiency. Notably, we identified TKI-resistant states of transient nature that correlate with alterations in KIT expression and can be reversed upon brief inhibitor withdrawal. These findings indicate that discontinuing treatment maintains dasatinib sensitivity in KIT(mut) AML cells. PMID- 24211244 TI - Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep. AB - The flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10mg/kg). At 3, 24, 48 and 60h post-treatment (pt), animals were sacrificed (n=3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8MUg/mL (TCBZ.SO) and 12.6MUg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35MUg/g (TCBZ.SO) and 13.9MUg/g (TCBZ.SO2) at 24h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14MUg/g at 24h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1MUg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites. However, the presence of TCBZ within the adult fluke (despite being absent in the systemic circulation) may be related to some degree of trans-tegumental diffusion from bile or by a direct oral ingestion from portal blood. PMID- 24211245 TI - Progress on retinal image analysis for age related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ~1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which include diagnosis and management of AMD, and how automated disease grading could benefit telemedicine. As there is no treatment for dry AMD and only early intervention can prevent the late AMD, we emphasize mass screening through a telemedicine platform to enable early detection of AMD. We also provide a comparative study between the imaging modalities and identify potential study areas for further improvement and future research direction in automated AMD grading and screening. PMID- 24211246 TI - Nature-via-nurture and unravelling causality in evolutionary genetics. AB - Quantitative geneticists traditionally attribute phenotypic variation to genetic or environmental sources. New findings with near-clonal mice raised in a single enriched environment demonstrated significant developmental and behavioural divergence. This suggests intriguing possibilities for how (epi)genomes and environments might interact to drive phenotypic individuality, thus shaping evolutionary pathways. PMID- 24211247 TI - On current utility and adaptive significance: a response to Nesse. PMID- 24211248 TI - Influence of glenoid component design and humeral component retroversion on internal and external rotation in reverse shoulder arthroplasty: a cadaver study. AB - BACKGROUND: A common disadvantage of reverse shoulder arthroplasty is limitation of the range of arm rotation. Several changes to the prosthesis design and implantation technique have been suggested to improve rotation range of motion (ROM). HYPOTHESIS: Glenoid component design and degree of humeral component retroversion influence rotation ROM after reverse shoulder arthroplasty. MATERIAL AND METHODS: The Aequalis ReversedTM shoulder prosthesis (Tornier Inc., Edina, MN, USA) was implanted into 40 cadaver shoulders. Eight glenoid component combinations were tested, five with the 36-mm sphere (centred seating, eccentric seating, inferior tilt, centred with a 5-mm thick lateralised spacer, and centred with a 7-mm thick lateralised spacer) and three with the 42-mm sphere (centred with no spacer or with a 7-mm or 10-mm spacer). Humeral component position was evaluated with 0 degrees , 10 degrees , 20 degrees , 30 degrees , and 40 degrees of retroversion. External and internal rotation ROMs to posterior and anterior impingement on the scapular neck were measured with the arm in 20 degrees of abduction. RESULTS: The large glenosphere (42 mm) was associated with significantly (P<0.05) greater rotation ROMs, particularly when combined with a lateralised spacer (46 degrees internal and 66 degrees external rotation). Rotation ROMs were smallest with the 36-mm sphere. Greater humeral component retroversion was associated with a decrease in internal rotation and a significant increase (P<0.05) in external rotation. The best balance between rotation ROMs was obtained with the native retroversion, which was estimated at 17.5 degrees on average in this study. DISCUSSION: Our anatomic study in a large number of cadavers involved a detailed and reproducible experimental protocol. However, we did not evaluate the variability in scapular anatomy. Earlier studies of the influence of technical parameters did not take humeral component retroversion into account. In addition, no previous studies assessed rotation ROMs. CONCLUSION: Rotation ROM should be improved by the use of a large-diameter glenosphere with a spacer to lateralise the centre of rotation of the gleno humeral joint, as well as by positioning the humeral component at the patient's native retroversion value. PMID- 24211249 TI - The effect of environmental distractors incorporation into a CPT on sustained attention and ADHD diagnosis among adolescents. AB - BACKGROUND: Diagnosis of ADHD in adolescents involves specific challenges. Conventional CPT's may fail to consistently distinguish ADHD from non-ADHD due to insufficient cognitive demands. The aim of this study was to explore whether the incorporation of environmental distractors into a CPT would increase its ability to distinguish ADHD from non-ADHD adolescents. NEW METHOD: Using the rate of omission errors as a measure of difficulty in sustained attention, this study examined whether ADHD adolescents are more distracted than controls and which type of distractors is more effective in terms of ADHD diagnosis. The study employed the MOXO-CPT version which includes visual and auditory stimuli serving as distractors. Participants were 176 adolescents aged 13-18 years, 133 diagnosed with ADHD and 43 without ADHD. RESULTS AND COMPARISON WITH EXISTING METHODS: Results showed that ADHD adolescents produced significantly more omission errors in the presence of pure visual distractors and the combination of visual and auditory distractors than in no-distractors conditions. Distracting stimuli had no effect on CPT performance of non-ADHD adolescents. ROC analysis further demonstrated that the mere presence of distractors improved the utility of the test. CONCLUSIONS: This study provides evidence that incorporation of environmental distractors into a CPT is useful in term of ADHD diagnosis. ADHD adolescents were more distracted than controls by all types of environmental distractors. ADHD adolescents were more distracted by pure visual distractors and by the combination of distractors than by pure auditory ones. PMID- 24211251 TI - Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins. AB - BACKGROUND: IDPs function without relying on three-dimensional structures. No clear rationale for such a behavior is available yet. PreSMos are transient secondary structures observed in the target-free IDPs and serve as the target binding "active" motifs in IDPs. Prolines are frequently found in the flanking regions of PreSMos. Contribution of prolines to the conformational stability of the helical PreSMos in IDPs is investigated. METHODS: MD simulations are performed for several IDP segments containing a helical PreSMo and the flanking prolines. To measure the influence of flanking-prolines on the structural content of a helical PreSMo calculations were done for wild type as well as for mutant segments with Pro->Asp, His, Lys, or Ala. The change in the helicity due to removal of a proline was measured both for the PreSMo region and for the flanking regions. RESULTS: The alpha-helical content in ~70% of the helical PreSMos at the early stage of simulation decreases due to replacement of an N-terminal flanking proline by other residues whereas the helix content in nearly all PreSMos increases when the same replacements occur at the C-terminal flanking region. The helix destabilizing/terminating role of the C-terminal flanking prolines is more pronounced than the helix promoting effect of the N-terminal flanking prolines. GENERAL SIGNIFICANCE: This work represents a novel example demonstrating that a proline is encoded in an IDP with a defined purpose. The helical PreSMos presage their target-bound conformations. As they most likely mediate IDP-target binding via conformational selection their helical content can be an important feature for IDP function. PMID- 24211252 TI - Autocrine GM-CSF transcription in the leukemic progenitor cell line KG1a is mediated by the transcription factor ETS1 and is negatively regulated through SECTM1 mediated ligation of CD7. AB - BACKGROUND: CD7 expression is found on ~30% of acute myeloblastic leukemias (AML). The leukemic progenitor cell line KG1a (CD7+) constitutively expresses GM CSF while the parental KG1 (CD7-) cell line does not. This study focuses on the molecular basis of CD7 mediated GM-CSF regulation. METHODS: KG1a cells were treated with recombinant SECTM1-Fc protein, the PI3K kinase inhibitors wortmannin, LY292004, or PI4K activator spermine. Stable KG1-CD7+, KG1a-shCD7, KG1a-shETS1 as well as KG1a-GFP, KG1a-PKCbetaII-GFP cell lines were generated and the levels of CD7, GM-CSF and ETS-1 mRNA and protein were compared by real-time PCR, western blotting, flow cytometry and ELISA. RESULTS: SECTM1 is expressed in Human Bone Marrow Endothelial Cells (HBMEC) and its expression can be upregulated by both IFN-gamma. KG1a cells demonstrated high expression levels of CD7 and ETS 1 allowing a constitutative signaling through the PI3K/Atk pathway to promote GM CSF expression, while KG1 cells with low expression of CD7 and ETS-1 showed low GM-CSF expression. On KG1a cells GM-CSF expression could be negatively regulated by PI3K inhibitors or by recombinant SECTM1-Fc. Overexpression of CD7 in KG1 cells was insufficient to promote GM-CSF expression, while silencing of CD7 or ETS-1 resulted in reduced GM-CSF expression levels. Differentiation capable KG1a cells overexpressing PKCbetaII illustrated complete loss of CD7, but maintained normal levels of both ETS-1 and GM-CSF expression. CONCLUSION: These findings add an additional layer to the previously described autocrine/paracrine signaling between leukemic progenitor cells and the bone marrow microenvironment and highlight a role for SECTM1 in both normal and malignant hematopoiesis. GENERAL SIGNIFICANCE: This work shows that SECTM1 secreted from bone marrow stromal cells may interact with CD7 to influence GM-CSF expression in leukemic cells. PMID- 24211250 TI - Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. AB - BACKGROUND: The maintenance of cell metabolism and homeostasis is a fundamental characteristic of living organisms. In eukaryotes, mitochondria are the cornerstone of these life supporting processes, playing leading roles in a host of core cellular functions, including energy transduction, metabolic and calcium signalling, and supporting roles in a number of biosynthetic pathways. The possession of a discrete mitochondrial genome dictates that the maintenance of mitochondrial 'fitness' requires quality control mechanisms which involve close communication with the nucleus. SCOPE OF REVIEW: This review explores the synergistic mechanisms that control mitochondrial quality and function and ensure cellular bioenergetic homeostasis. These include antioxidant defence mechanisms that protect against oxidative damage caused by reactive oxygen species, while regulating signals transduced through such free radicals. Protein homeostasis controls import, folding, and degradation of proteins underpinned by mechanisms that regulate bioenergetic capacity through the mitochondrial unfolded protein response. Autophagic machinery is recruited for mitochondrial turnover through the process of mitophagy. Mitochondria also communicate with the nucleus to exact specific transcriptional responses through retrograde signalling pathways. MAJOR CONCLUSIONS: The outcome of mitochondrial quality control is not only reliant on the efficient operation of the core homeostatic mechanisms but also in the effective interaction of mitochondria with other cellular components, namely the nucleus. GENERAL SIGNIFICANCE: Understanding mitochondrial quality control and the interactions between the organelle and the nucleus will be crucial in developing therapies for the plethora of diseases in which the pathophysiology is determined by mitochondrial dysfunction. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. PMID- 24211253 TI - MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer. AB - Mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) as well as Yes-associated protein (YAP), the downstream effector of Hippo signaling pathway, is linked to hepatocarcinogenesis. However, little is known about whether and how MEK1 interacts with YAP. In this study, we find that MEK1-YAP interaction is critical for liver cancer cell proliferation and maintenance of transformed phenotypes both in vitro and in vivo. Moreover, MEK1 and YAP proteins are closely correlated in human liver cancer samples. Mechanistically, inhibition of MEK1 by both PD98059 and U0126 as well as RNAi reduces beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), which acts as a potential endogenous YAP protector. PMID- 24211254 TI - Identification of fungal microorganisms by MALDI-TOF mass spectrometry. AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a reliable tool for fast identification and classification of microorganisms. In this regard, it represents a strong challenge to microscopic and molecular biology methods. Nowadays, commercial MALDI systems are accessible for biological research work as well as for diagnostic applications in clinical medicine, biotechnology and industry. They are employed namely in bacterial biotyping but numerous experimental strategies have also been developed for the analysis of fungi, which is the topic of the present review. Members of many fungal genera such as Aspergillus, Fusarium, Penicillium or Trichoderma and also various yeasts from clinical samples (e.g. Candida albicans) have been successfully identified by MALDI-TOF MS. However, there is no versatile method for fungi currently available even though the use of only a limited number of matrix compounds has been reported. Either intact cell/spore MALDI-TOF MS is chosen or an extraction of surface proteins is performed and then the resulting extract is measured. Biotrophic fungal phytopathogens can be identified via a direct acquisition of MALDI-TOF mass spectra e.g. from infected plant organs contaminated by fungal spores. Mass spectrometric peptide/protein profiles of fungi display peaks in the m/z region of 1000-20000, where a unique set of biomarker ions may appear facilitating a differentiation of samples at the level of genus, species or strain. This is done with the help of a processing software and spectral database of reference strains, which should preferably be constructed under the same standardized experimental conditions. PMID- 24211255 TI - Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation. AB - The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the beta-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24 h memory for objects, which was impaired by co-administration of propranolol (0.5MUg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation. PMID- 24211256 TI - Nogo-A downregulation impairs place avoidance in the Carousel maze but not spatial memory in the Morris water maze. AB - Nogo-A protein is an important inhibitor of axonal growth, which also regulates neuronal plasticity in the CNS. Mutations in the gene encoding Nogo-A or abnormalities in Nogo-A expression are linked to neuropsychiatric disorders such as schizophrenia. The present study assesses the impact of constitutively reduced expression of Nogo-A on place navigation in a novel transgenic rat model. Two spatial paradigms were used: (1) A battery of tests in the Carousel maze requiring continuous processing of spatial information with increasing demands for the segregation of reference frames and behavioral flexibility and (2) a delayed-matching-to-place version of the Morris water maze (MWM), which requires place navigation and is sensitive to deficits in one-trial-encoded place representation. The Carousel maze testing revealed a subtle but significant impairment in management of reference frames. Matching-to-place learning in the Morris water maze was unaffected, suggesting an intact representation of an unmarked goal. Our results show that Nogo-A deficiency leads to cognitive deficit in processing of the reference frames. Such a deficit may be the result of neuro developmental alterations resulting from Nogo-A deficiency. PMID- 24211257 TI - On the analytical solution for the Putter-Bertalanffy growth equation. AB - This study develops the basic idea of Putter and Bertalanffy addressing the allometric scaling of anabolism and catabolism on somatic growth dynamics. We proposed a standardized form of the Putter-Bertalanffy equation (PBE), which is given as the extended model of Richards function, and subsequently solved it. The analytical solution of the PBE was defined by an incomplete beta function and can take a wide range of shapes in its growth curve. The mathematical behavior of PBE due to the change in parameter values was briefly discussed. Most forms of solution consistently hold the implicit functional type with respect to the variable of body size. PMID- 24211258 TI - Kernel methods for phenotyping complex plant architecture. AB - The Quantitative Trait Loci (QTL) mapping of plant architecture is a critical step for understanding the genetic determinism of plant architecture. Previous studies adopted simple measurements, such as plant-height, stem-diameter and branching-intensity for QTL mapping of plant architecture. Many of these quantitative traits were generally correlated to each other, which give rise to statistical problem in the detection of QTL. We aim to test the applicability of kernel methods to phenotyping inflorescence architecture and its QTL mapping. We first test Kernel Principal Component Analysis (KPCA) and Support Vector Machines (SVM) over an artificial dataset of simulated inflorescences with different types of flower distribution, which is coded as a sequence of flower-number per node along a shoot. The ability of discriminating the different inflorescence types by SVM and KPCA is illustrated. We then apply the KPCA representation to the real dataset of rose inflorescence shoots (n=1460) obtained from a 98 F1 hybrid mapping population. We find kernel principal components with high heritability (>0.7), and the QTL analysis identifies a new QTL, which was not detected by a trait-by-trait analysis of simple architectural measurements. The main tools developed in this paper could be use to tackle the general problem of QTL mapping of complex (sequences, 3D structure, graphs) phenotypic traits. PMID- 24211259 TI - DNA strand displacement system running logic programs. AB - The paper presents a DNA-based computing model which is enzyme-free and autonomous, not requiring a human intervention during the computation. The model is able to perform iterated resolution steps with logical formulae in conjunctive normal form. The implementation is based on the technique of DNA strand displacement, with each clause encoded in a separate DNA molecule. Propositions are encoded assigning a strand to each proposition p, and its complementary strand to the proposition !p; clauses are encoded comprising different propositions in the same strand. The model allows to run logic programs composed of Horn clauses by cascading resolution steps. The potential of the model is demonstrated also by its theoretical capability of solving SAT. The resulting SAT algorithm has a linear time complexity in the number of resolution steps, whereas its spatial complexity is exponential in the number of variables of the formula. PMID- 24211260 TI - Perfusion and vascular permeability: basic concepts and measurement in DCE-CT and DCE-MRI. AB - The microvascular network formed by the capillaries supplies the tissues and permits their function. It provides a considerable surface area for exchanges between blood and tissues. All pathological conditions cause changes in the microcirculation. These changes can be used as imaging biomarkers for the diagnosis of lesions and optimisation of treatment. Among the many imaging techniques developed to study the microcirculation, the analysis of the tissue kinetics of intravenously injected contrast agents is the most widely used, either as positive enhancement for CT, T1-weighted MRI and ultrasound - dynamic contrast-enhanced-imaging (DCE-imaging) - or negative enhancement in T2*-weighted brain MRI - dynamic susceptibility contrast-MRI (DSC-MRI) -. Acquisition involves an injection of contrast agent during the acquisition of a dynamic series of images on a zone of interest. These kinetics may be analyzed visually, to define qualitative criteria, or with software using mathematical modelling, to extract quantitative physiological parameters. The results depend on the acquisition conditions (type of imaging device, imaging mode, frequency and total duration of acquisition), the type of contrast agent, the data pre-processing (motion correction, conversion of the signal into concentration) and the data analysis method. Because of these multiple choices it is necessary to understand the physiological processes involved and understand the advantages and limits of each strategy. PMID- 24211261 TI - Prostate MRI: can we do without DCE sequences in 2013? AB - Multiparametric MRI (mp-MRI) of the prostate currently provides stable and reproducible performances. The usefulness of dynamic contrast-enhanced (DCE) sequences is currently challenged, as they sometimes only confirm what has already been observed on diffusion-weighted imaging (DWI) and require the additional purchase of a contrast agent. Eliminating these sequences may help accelerate the use of MRI in addition to, or in lieu of, prostate biopsies in selected patients. However, many studies show that these sequences can detect lesions invisible on T2-weighted and diffusion-weighted images, better assess cancer extension and aggressiveness, and finally help detecting recurrence after treatment. We present the various applications of dynamic MRI and discuss the possible consequences of its omission from the current protocol. PMID- 24211262 TI - Potential problems in the determination of serum non-transferrin-bound iron using nitrilotriacetic acid and ultrafiltration. PMID- 24211264 TI - R loops are linked to histone H3 S10 phosphorylation and chromatin condensation. AB - R loops are transcription byproducts that constitute a threat to genome integrity. Here we show that R loops are tightly linked to histone H3 S10 phosphorylation (H3S10P), a mark of chromatin condensation. Chromatin immunoprecipitation (ChIP)-on-chip (ChIP-chip) analyses reveal H3S10P accumulation at centromeres, pericentromeric chromatin, and a large number of active open reading frames (ORFs) in R-loop-accumulating yeast cells, better observed in G1. Histone H3S10 plays a key role in maintaining genome stability, as scored by ectopic recombination and plasmid loss, Rad52 foci, and Rad53 checkpoint activation. H3S10P coincides with the presence of DNA-RNA hybrids, is suppressed by ribonuclease H overexpression, and causes reduced accessibility of restriction endonucleases, implying a tight connection between R loops, H3S10P, and chromatin compaction. Such histone modifications were also observed in R-loop accumulating Caenorhabditis elegans and HeLa cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics. PMID- 24211263 TI - Genome-wide consequences of deleting any single gene. AB - Loss or duplication of chromosome segments can lead to further genomic changes associated with cancer. However, it is not known whether only a select subset of genes is responsible for driving further changes. To determine whether perturbation of any given gene in a genome suffices to drive subsequent genetic changes, we analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild-type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat stress-induced cell death. Moreover, independent knockouts of the same gene often evolved mutations in the same secondary gene. Genome sequencing identified acquired mutations in several human tumor suppressor homologs. Thus, mutation of any single gene may cause a genomic imbalance, with consequences sufficient to drive adaptive genetic changes. This complicates genetic analyses but is a logical consequence of losing a functional unit originally acquired under pressure during evolution. PMID- 24211265 TI - The structural basis of FtsY recruitment and GTPase activation by SRP RNA. AB - The universally conserved signal recognition particle (SRP) system mediates the targeting of membrane proteins to the translocon in a multistep process controlled by GTP hydrolysis. Here we present the 2.6 A crystal structure of the GTPase domains of the E. coli SRP protein (Ffh) and its receptor (FtsY) in complex with the tetraloop and the distal region of SRP-RNA, trapped in the activated state in presence of GDP:AlF4. The structure reveals the atomic details of FtsY recruitment and, together with biochemical experiments, pinpoints G83 as the key RNA residue that stimulates GTP hydrolysis. Insertion of G83 into the FtsY active site orients a single glutamate residue provided by Ffh (E277), triggering GTP hydrolysis and complex disassembly at the end of the targeting cycle. The complete conservation of the key residues of the SRP-RNA and the SRP protein implies that the suggested chemical mechanism of GTPase activation is applicable across all kingdoms. PMID- 24211266 TI - An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth. AB - SHOC2 is mutated in Noonan syndrome and plays a key role in the activation of the ERK-MAPK pathway, which is upregulated in the majority of human cancers. SHOC2 functions as a PP1-regulatory protein and as an effector of MRAS. Here we show that SHOC2 and MRAS form a complex with SCRIB, a polarity protein with tumor suppressor properties. SCRIB functions as a PP1-regulatory protein and antagonizes SHOC2-mediated RAF dephosphorylation through a mechanism involving competition for PP1 molecules within the same macromolecular complex. SHOC2 function is selectively required for the malignant properties of tumor cells with mutant RAS, and both MRAS and SHOC2 play a key role in polarized migration. We propose that MRAS, through its ability to recruit a complex with paradoxical components, coordinates ERK pathway spatiotemporal dynamics with polarity and that this complex plays a key role during tumorigenic growth. PMID- 24211267 TI - Amylopectin is the anti-fatigue ingredient in glutinous rice. AB - The anti-fatigue activities of glutinous rice (GR) and GR amylopectin (GRA) were investigated in mice by determining tissue glycogen, blood lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) after the weight loaded forced swim test (WFST). GR and GRA were given by gavage at various doses of GR (7.5, 15, 30 g/kg body weight) and GRA (3.8, 7.5, 15 g/kg body weight) every day for 7 days, respectively. The results indicated that the hepatic glycogen levels significantly (P<0.05) increased 26-44% and 35-60% and the muscle glycogen levels significantly (P<0.05) increased 36-100% and 67-133% in GR and GRA treatment groups, compared with the negative control group. The GRA treatment groups also had significantly (P<0.05) higher (9.1-20.3%) blood LDH levels. Meanwhile, the blood LDH activities in GR and GRA treatment groups had a significantly positive correlation with the hepatic glycogen levels (r=0.978, P<0.01). Moreover, except of the low-dose GR (7.5 g/kg body weight) supplemented group, mice in all other treatment groups had significantly (P<0.05) lower (13-23%) BUN levels. Compared with the GR treatment groups, GRA treatment groups had similar or even higher anti-fatigue activities, which demonstrated that GRA might play the most important role on the anti-fatigue activities for GR. PMID- 24211268 TI - Does the stability of proteins in ionic liquids obey the Hofmeister series? AB - Understanding the behavior of Hofmeister anions of ionic liquids (ILs) on protein stability helps to shed light on how the anions interact with proteins in aqueous solution and is a long standing object for chemistry and biochemistry. Ions effects play a major role in understanding the physicochemical and biological phenomenon that undertakes the protein folding/unfolding and refolding process. Despite the generality of these effects, our understanding of ions at the molecular-level is still limited. This review offers a tour through past successful investigations and presents a challenge in current research in the field to reassess the possibilities of ions and to apply new strategies. This review highlights on the stability behavior of the proteins and also comparisons of our past research work in the Hofmeister series of ILs. Furthermore, we specifically focus on the critical discussion on the recent findings with existing results and their implications, along with our understanding of the Hofmeister series of anions of ILs on biomolecular stability. A detailed examination of the difference between selective proteins can provide a better understanding of the molecular mechanism of protein folding/unfolding in the presence of the Hofmeister series of ions of ILs. PMID- 24211269 TI - A crab with three eyes, two rostra, and a dorsal antenna-like structure. AB - We describe a malformed specimen of the freshwater crab Amarinus lacustris from New Zealand. With three eyes in a horizontal row, two rostra, and a dorsal antenna-like structure, the pattern of malformation of this animal is unique and has not been described before. A careful inspection and description of external and internal structures, in particular the central nervous system, were carried out. These revealed, in addition to the external abnormalities, a retarded brain with a hypertrophied and backwards bent protocerebrum connected with all three eyes and putatively with the dorsal antenna-like structure. Based on these data, a variety of hypotheses about the causes for this kind of malformation are discussed. A scenario combining a conjoined twin (Duplicitas anterior) based on the duplication of the embryonic anterior head lobes and a regeneration event leading to the replacement of an eye by an antenna shows the best fit to the observed patterns. PMID- 24211270 TI - The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide. AB - Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitumor activity; the inhibitory mechanism, however, is still unclear. In the present study, we found that treatment with [Ru(CO)3Cl2]2 (RuCO), a CO-releasing compound, reduced the growth of human MCF7 and MDA-MB-231 breast cancer cells. Analysis of growth-related proteins showed that treatment with RuCO down-regulated cyclinD1, CDK4, and hTERT protein expressions. Interestingly, RuCO treatment resulted in opposite effects on wild-type and mutant p53 proteins. These results were similar to those of cells treated with geldanamycin (a heat shock protein (HSP)90 inhibitor), suggesting that RuCO might affect HSP90 activity. Moreover, RuCO induced mutant p53 protein destabilization accompanied by promotion of ubiquitination and proteasome degradation. The induction of HO-1 by cobalt protoporphyrin IX (CoPP) showed consistent results, while the addition of tin protoporphyrin IX (SnPP), an HO-1 enzymatic inhibitor, diminished the RuCO-mediated effect. RuCO induction of HO-1 expression was reduced by a p38 mitogen-activated protein kinase inhibitor (SB203580). Additionally, treatment with a chemopreventive compound, curcumin, induced HO-1 expression accompanied with reduction of HSP90 client protein expression. The induction of HO-1 by curcumin inhibited 12-O-tetradecanoyl-13 acetate (TPA)-elicited matrix metalloproteinase-9 expression and tumor invasion. In conclusion, we provide novel evidence underlying HO-1's antitumor mechanism. CO, a byproduct of HO-1, suppresses HSP90 protein activity, and the induction of HO-1 may possess potential as a cancer therapeutic. PMID- 24211271 TI - Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: impact on NOX-1, inflammation and apoptosis. AB - Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1beta, TNF-alpha, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is partially involved in the pathogenesis of cispaltin-induced nephrotoxicity. PMID- 24211272 TI - Hepatocyte-based in vitro model for assessment of drug-induced cholestasis. AB - Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24-48h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI<=0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI<=0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. PMID- 24211273 TI - Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death. AB - The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497 C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB1 receptor antagonist AM251, but not with the selective CB2 receptor antagonist AM630. Furthermore, annexin-V positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB1 receptor, but not by the CB2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. PMID- 24211275 TI - Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice. AB - Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180mJ/cm(2)) three times a week for 24weeks. The development of UVB induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P<0.01-0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (P<0.01), and PGE2 receptors, and activation of NF-kappaB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-alpha (P<0.01), interleukin (IL)-1beta (P<0.01) and IL-6 (P<0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser(473) in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. PMID- 24211274 TI - CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+ T cells aid progression of environment-linked nonalcoholic steatohepatitis. AB - Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression. To identify the relevant subsets of T-lymphocytes in CYP2E1-dependent, environment-linked NASH, we utilized a model of diet induced obese (DIO) mice that are chronically exposed to bromodichloromethane. Mice deficient in CYP2E1, leptin (ob/ob mice), or both T and B cells (Pfp/Rag2 double knockout (KO) mice) were used to delineate the role of each of these factors in metabolic oxidative stress-induced T cell activation. Results revealed that elevated levels of lipid peroxidation, tyrosyl radical formation, mitochondrial tyrosine nitration and hepatic leptin as a consequence of metabolic oxidative stress caused increased levels of hepatic CD57, a marker of peripheral blood lymphocytes including NKT cells. CD8+CD57+ cytotoxic T cells but not CD4+CD57+ cells were significantly decreased in mice lacking CYP2E1 and leptin. There was a significant increase in the levels of T cell cytokines IL-2, IL-1beta, and IFN-gamma in bromodichloromethane exposed DIO mice but not in mice that lacked CYP2E1, leptin or T and B cells. Apoptosis as evidenced by TUNEL assay and levels of cleaved caspase-3 was significantly lower in leptin and Pfp/Rag2 KO mice and highly correlated with protection from NASH. The results described above suggest that higher levels of oxidative stress-induced leptin mediated CD8+CD57+ T cells play an important role in the development of NASH. It also provides a novel insight of immune dysregulation and may be a key biomarker in NASH. PMID- 24211276 TI - Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes. AB - Isorhamentin is a 3'-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCdelta and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes. PMID- 24211277 TI - Using a single cut-off for stress hyperglycemia in myocardial infarction decreases its prognostic value particularly in diabetes. PMID- 24211278 TI - Physical maneuvers: effective but underutilized treatment of benign paroxysmal positional vertigo in the ED. PMID- 24211279 TI - Caffeine-induced rhabdomyolysis. PMID- 24211280 TI - Computer-based reminder system effectively impacts physician documentation. PMID- 24211281 TI - Safety of a rapid diagnostic protocol with accelerated stress testing. AB - BACKGROUND: Most patients at low to intermediate risk for an acute coronary syndrome (ACS) receive a 12- to 24-hour "rule out." Recently, trials have found that a coronary computed tomographic angiography-based strategy is more efficient. If stress testing were performed within the same time frame as coronary computed tomographic angiography, the 2 strategies would be more similar. We tested the hypothesis that stress testing can safely be performed within several hours of presentation. METHODS: We performed a retrospective cohort study of patients presenting to a university hospital from January 1, 2009, to December 31, 2011, with potential ACS. Patients placed in a clinical pathway that performed stress testing after 2 negative troponin values 2 hours apart were included. We excluded patients with ST-elevation myocardial infarction or with an elevated initial troponin. The main outcome was safety of immediate stress testing defined as the absence of death or acute myocardial infarction (defined as elevated troponin within 24 hours after the test). RESULTS: A total of 856 patients who presented with potential ACS were enrolled in the clinical pathway and included in this study. Patients had a median age of 55.0 (interquartile range, 48-62) years. Chest pain was the chief concern in 86%, and pain was present on arrival in 73% of the patients. There were no complications observed during the stress test. There were 0 deaths (95% confidence interval, 0% 0.46%) and 4 acute myocardial infarctions within 24 hours (0.5%; 95% confidence interval, 0.14%-1.27%). The peak troponins were small (0.06, 0.07, 0.07, and 0.19 ng/mL). CONCLUSIONS: Patients who present to the ED with potential ACS can safely undergo a rapid diagnostic protocol with stress testing. PMID- 24211282 TI - Single-incision laparoscopic surgery for ingested foreign body removal. AB - This report presents a 16-year-old adolescent boy with intentional ingestion of a 6-cm-length iron nail in detention center 6 hours ago. There was no symptom and sign of acute abdominal pain. Abdominal computed tomographic scan was performed, and an iron nail was found in the left upper quadrant abdomen. Considering the size, shape, and location of the foreign body, emergency surgery was performed using single-incision laparoscopic surgery approach. Multiple trocars in umbilical incision technique and conventional instruments were used. After identification of the foreign body in jejunum by alternative clamping of small bowel, enterostomy was made, and extracorporeal suturing was performed. The operation time was 1 hour without blood loss during the surgery. The patient left the bed 6 hours after the surgery. Bowel function recovered, and the gastric tube was removed on postoperative day 2. No painkiller was used after the surgery. The patient was discharged on postoperative day 3 without any complication. To our knowledge, it is the first report on removal of ingested foreign body located in jejunum using single-incision laparoscopic surgery technique. PMID- 24211283 TI - Does chest radiograph confirm tracheal intubation? PMID- 24211284 TI - Utility of point-of-care ultrasound in acute management triage of earthquake injury. PMID- 24211285 TI - Recurrent central venous malposition caused by severe lower airway distortion. PMID- 24211286 TI - A case of tetanus infection in an adult with a protective tetanus antibody level. AB - Tetanus is a bacterial infection caused by Clostridium tetani and most commonly presents as trismus or other muscle spasms. Despite the development of the tetanus toxoid vaccine, tetanus infection has not been eradicated. Additionally, while there are hypothesized protective levels of tetanus antibody, tetanus infection may still occur in properly vaccinated individuals. We report the case of a 31-year-old male that presented to the emergency department (ED) with a 2 day history of neck and jaw pain. He reports puncturing his hand with a rusty nail 10 days prior. His reported vaccination history was that he received his last booster vaccination 13 years prior to presentation. In the ED, tetanus vaccine, tetanus immune globulin, and metronidazole were administered. His symptoms improved over the next 2 days and resolved at day 6. Despite his presentation of tetanus infection and rule out of other causes for his symptoms, his tetanus antibody level was reported at 8.4 U/mL, which is considered to be protective.A tetanus antibody level that is adequate for protective immunity should not preclude a patient from treatment of tetanus infection. This case demonstrates that a thorough history, physical exam, and rule out of other causes should guide treatment when there is concern for a tetanus infection. PMID- 24211287 TI - A new facial expression to botox! AB - Botulinum toxin (Botox) injection into the lower esophageal sphincter (LES) has been used for the treatment of achlasia cardia since the 1990s. Currently it is indicated for patients who are not candidates for definitive therapy like Heller's myotomy or pneumatic dilation and in those who have recurrence of symptoms after definitive treatments. We present a case of severe anaphylaxix due to Botox. The purpose of this case is to highlight one of the under-reported adverse effects of Botox. Anaphylactic reactions to Botox are very rare with only one other case being reported and have not been emphasized enough to be widely known in clinical practice. PMID- 24211288 TI - The unfolding story of celiac disease risk factors. PMID- 24211289 TI - The liver breath! Breath volatile organic compounds for the diagnosis of liver disease. PMID- 24211290 TI - Factors that contribute to hypertransaminasemia in patients with celiac disease or functional gastrointestinal syndromes. AB - BACKGROUND & AIMS: Transaminasemia develops via different pathways in patients with celiac disease; no information is available on risk factors specifically attributable to celiac disease. METHODS: We analyzed data collected from consecutive patients referred from January 1997 through December 2009 to the celiac disease clinic at the Spedali Civili of Brescia, Italy. We assessed the factors affecting hypertransaminasemia in 683 patients with celiac disease (based on serologic and biopsy analysis, cohort A; 34 +/- 14 years of age) and 304 with functional syndromes (cohort B; 37 +/- 13 years of age). RESULTS: Hypertransaminasemia was detected in 138 patients in cohort A (20%). It was associated with malabsorption (odds ratio [OR], 2.22; P = .004), diarrhea (OR, 1.72; P = .005), and increasing severity of mucosal lesion (Marsh-Oberhuber class; OR, 1.46; P = .001) but not with body mass index (BMI) or the serum level of tissue-transglutaminase antibodies (tTG). Hypertransaminasemia was detected in 22 patients in cohort B (7%) and was associated with the World Health Organization's BMI categories (OR, 7.9; P < .001). In subsets of patients studied with the same analytical method (313 of cohort A and 188 of cohort B), the level of tTG was significantly higher in cohort A at baseline (25.2 +/- 16.9 U/L aspartate aminotransferase [AST]) than in cohort B (20.6 +/- 9.9 U/L AST, P < .0001) and was related to BMI in cohort B (P = .0012) but not cohort A. When patients were placed on gluten-free diets, the levels of AST decreased from 25.2 +/- 16.9 U/L to 19.9 +/- 6.6 U/L (P < .0001), independently of the changes of duodenal histology and tTG and correlated with BMI (P = .0007); the prevalence of hypertransaminasemia decreased from 13% to 4%. CONCLUSIONS: Patients with celiac disease have a higher prevalence of hypertransaminasemia than controls (patients with functional syndromes). Hypertransaminasemia is related to the severity of the duodenal lesion and malabsorption but not BMI. By contrast, there was a positive correlation between the levels of AST and BMI in controls; this relationship was restored when patients with celiac disease were placed on gluten free diets. PMID- 24211291 TI - Macroscopic findings in lymphocytic colitis. PMID- 24211292 TI - Helicobacter pylori eradication and metachronous gastric cancer. PMID- 24211293 TI - Does chemotherapy cause viral relapse in cancer patients with hepatitis C infection successfully treated with antivirals? AB - Authors have reported conflicting results on the persistence of hepatitis C virus (HCV) infection in patients having sustained virologic response (SVR) to treatment. Therefore, we sought to determine whether chemotherapy leads to viral relapse in 30 HCV-infected patients who had SVR before cancer diagnosis. Half of them had hematologic malignancies. Most (60%) received HCV therapy with interferon and ribavirin. Chemotherapy was started at a median of 72 months after SVR and included rituximab (27%), cyclophosphamide (23%), cisplatin (17%), or corticosteroids (37%). No patient had post-SVR viral relapse. Therapeutically induced resolution of HCV appears to be permanent and not affected by chemotherapy. PMID- 24211294 TI - Transfection of pseudouridine-modified mRNA encoding CPD-photolyase leads to repair of DNA damage in human keratinocytes: a new approach with future therapeutic potential. AB - UVB irradiation induces harmful photochemical reactions, including formation of Cyclobutane Pyrimidine Dimers (CPDs) in DNA. Accumulation of unrepaired CPD lesions causes inflammation, premature ageing and skin cancer. Photolyases are DNA repair enzymes that can rapidly restore DNA integrity in a light-dependent process called photoreactivation, but these enzymes are absent in humans. Here, we present a novel mRNA-based gene therapy method that directs synthesis of a marsupial, Potorous tridactylus, CPD-photolyase in cultured human keratinocytes. Pseudouridine was incorporated during in vitro transcription to make the mRNA non immunogenic and highly translatable. Keratinocytes transfected with lipofectamine complexed mRNA expressed photolyase in the nuclei for at least 2days. Exposing photolyase mRNA-transfected cells to UVB irradiation resulted in significantly less CPD in those cells that were also treated with photoreactivating light, which is required for photolyase activity. The functional photolyase also diminished other UVB-mediated effects, including induction of IL-6 and inhibition of cell proliferation. These results demonstrate that pseudouridine-containing photolyase mRNA is a powerful tool to repair UVB-induced DNA lesions. The pseudouridine-modified mRNA approach has a strong potential to discern cellular effects of CPD in UV-related cell biological studies. The mRNA-based transient expression of proteins offers a number of opportunities for future application in medicine. PMID- 24211295 TI - The agr function and polymorphism: impact on Staphylococcus aureus susceptibility to photoinactivation. AB - Staphylococcus aureus is an important human pathogen that causes healthcare associated and community-acquired infections. Moreover, the growing prevalence of multiresistant strains requires the development of alternative methods to antibiotic therapy. One effective therapeutic option may be antimicrobial photodynamic inactivation (aPDI). Recently, S. aureus strain-dependent response to PDI was demonstrated, although the mechanism underlying this phenomenon remains unexplained. The aim of the current study was to investigate statistically relevant correlations between the functionality and polymorphisms of agr gene determined for 750 methicillin-susceptible and methicillin-resistant S. aureus strains and their responses to photodynamic inactivation using protoporphyrin IX. An AluI and RsaI digestion of the agr gene PCR product revealed existing correlations between the determined digestion profiles (designations used for the first time) and the PDI response. Moreover, the functionality of the agr system affected S. aureus susceptibility to PDI. Based on our results, we conclude that the agr gene may be a genetic factor affecting the strain dependent response to PDI. PMID- 24211296 TI - Fluorescence lifetime distributions report on protein destabilisation in quenching experiments. AB - Tryptophan is the most often investigated intrinsic fluorophore due to its abundance in proteins and its sensitivity to different environmental conditions. Fluorescence quenching is a powerful method to study proteins and acrylamide is a frequently applied quencher in these investigations. Quenching experiments are sometimes distorted by the undesired protein-quencher interactions that can result in a misinterpretation of the results. Here we focused on the identification of the possible side-effects of acrylamide applying fluorescence lifetime measurements. To provide reference data for protein denaturation the fluorescence parameters were also recorded in the presence of different concentrations of guanidine hydrochloride. In circular dichroism experiments we characterized directly the acrylamide effect on the tertiary structure of the proteins. According to the obtained data in experiments with seven tryptophan containing proteins the full width at half maximum (FWHM) of the fluorescence lifetime distribution is an appropriate parameter to monitor the undesired effects of acrylamide on the proteins. PMID- 24211297 TI - Development and comparison of a quantitative TaqMan-MGB real-time PCR assay to three other methods of quantifying vaccinia virions. AB - Plaque assays are a widely used method to quantify stocks of viruses. Although this method is well established for titrating viral stocks, it is time consuming and can take several days to complete. In this study, the creation and validation of a quantitative real-time PCR (qPCR) assay for enumerating virions of vaccinia virus is reported. PCR primers and a minor groove-binding probe were designed to hybridize to the DNA polymerase gene (E9L) from a number of different orthopoxviruses. The number of viral genomes determined using qPCR was approximately similar to results obtained using OD260 measurements and a direct count of fluorescent virions by microscopy indicating that all three methods are comparable in their ability to quantify virions from a purified stock. In addition, this report describes methodologies to harvest and quantify, using the qPCR assay, three of the four types of vaccinia virions produced during morphogenesis: intracellular mature virions, cell-associated enveloped virions, and extracellular enveloped virions. Using these procedures a particle to plaque forming unit of 61:1, 14:1 and 6:1 was calculated for IMV, CEV and EEV, respectively. These results show that qPCR can be used as a fast and accurate assay to quantify stocks of vaccinia virus over several orders of magnitude from both purified and unpurified stocks and should be applicable to other members of the orthopoxvirus genera. PMID- 24211298 TI - A double layer plaque assay using spread plate technique for enumeration of bacteriophage MS2. AB - Bacteriophage MS2 is used widely as a model organism to estimate pathogenic virus survival in various environments, and is usually quantified by plaque assay. Although current plaque assays work well in enumeration of MS2 in environmental samples, quantification of MS2 calls for better visibility and higher consistency. In an attempt to improve the visibility and consistency of the current plaque assay, spread plate technique was introduced, instead of the pour plate technique used commonly in existing methods. Other parameters that influence the outcome of the plaque assay were also compared. Using spread plate technique resulted in an increase of plaque size by approximately 50% and contributed to a better visibility. Addition of supplements (glucose, CaCl2 and thiamine); reduction of agar thickness and hardness, also contributed to enhanced plaque visibility and increased plaque count. Among all the conditions tested, a supplemented thin bottom agar (10ml 1% agar) and a supplemented thin top agar (10ml 0.45% agar) with spread plate technique gave the maximum countable plaques with a minimum standard deviation. When compared to other methods, it produced significantly higher plaque count and lower variation. The optimized plaque assay significantly improved visibility and consistency of the existing plaque assay methods and could be used in quantification of MS2. PMID- 24211299 TI - Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease. AB - Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease. PMID- 24211300 TI - Characterization and sub-cellular localization of SS1R, SS2R, and SS5R in human late-stage prostate cancer cells: effect of mono- and bi-specific somatostatin analogs on cell growth. AB - Somatostatin (SST) and SST receptors (SS1R, SS2R, SS3R, SS4R and SS5R) appear to play a significant role in the progression of human prostate cancer (PCa), which is associated with heterogeneity of SSRs expression and specific cell localization as we already demonstrated in the LNCaP cell line, an in vitro model of human androgen-dependent PCa. In this study, PC-3 and DU-145 human castration resistant PCa cells were found to express all SSRs, while LNCaP expressed all but SS4R. A 48-h treatment with BIM-23244 (SS2R/SS5R) or BIM-23926 (SS1R) SST analogs was more effective in inhibiting cell proliferation, compared to BIM-23120 (SS2R), BIM-23206 (SS5R) and BIM-23704 (SS1R/SS2R). BIM-23926 (SS1R) treatment increased the amount of p21 and decreased phosphorylated (p) ERK1/2. BIM-23244 (SS2R/SS5R) led to p21 increment only in PC-3 cells, and to pERK1/2 reduction in both cell lines. SS1R/SS2R and SS2R/SS5R receptor dimers were natively present on cell membrane and their amount was increased by BIM-23704 (SS1R/SS2R) or BIM 23244 (SS2R/SS5R) treatment, respectively. SS1R, SS2R and SS5R were differently distributed among nuclear, lysosomal and microsomal compartment, according to their different recycling dynamics. These results show that, in PC-3, DU-145 and LNCaP cells, activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effects. PMID- 24211301 TI - AS1069562, the (+)-isomer of indeloxazine, but not duloxetine has a curative-like analgesic effect in a rat model of streptozotocin-induced diabetic neuropathy. AB - AS1069562 is the (+)-isomer of indeloxazine, which had been clinically used as a cerebral activator for the treatment of cerebrovascular diseases with serotonin and norepinephrine reuptake inhibition (SNRI) and neuroprotection. Here, we compared the analgesic effects of repeated treatment with AS1069562 and duloxetine, a selective SNRI, on pain-related behavior in a rat model of streptozotocin (STZ)-induced diabetic neuropathy. Further, we also evaluated the effects on the expression of neurotrophic factors and nerve conduction velocity. AS1069562 and duloxetine by single daily administration for 4 weeks significantly improved mechanical allodynia in STZ-induced diabetic rats and did not affect plasma glucose level or body weight. Interestingly, the analgesic effect of AS1069562 continued after a consecutive 1-week treatment discontinuation, although the plasma concentration of AS1069562 was reduced to undetectable levels. In contrast, the efficacy of duloxetine disappeared after treatment discontinuation. Expression analysis demonstrated that AS1069562 significantly restored decreased insulin-like growth factor 1 and fibroblast growth factor 2 mRNA levels in dorsal root ganglion and spinal cord, respectively, whereas duloxetine did not affect the expression levels of neurotrophic factors. In addition, AS1069562 reversed the slowing of nerve conduction velocity. The results of this study indicate that the analgesic effect of repeated dosing of AS1069562 but not duloxetine is persistent even after a 1-week drug discontinuation in STZ-induced diabetic rats. Restoration of neurotrophic factors may be involved in the curative-like pharmacological effect of this agent. Thus, AS1069562 may potentially offer a better treatment option for patients with painful diabetic neuropathy than duloxetine via different mechanisms. PMID- 24211302 TI - Ghrelin administration enhances neurogenesis but impairs spatial learning and memory in adult mice. AB - Ghrelin, an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents, was reported to enhance both adult neurogenesis and hippocampus-dependent memory formation. However, it is still unclear whether ghrelin-induced hippocampus neurogenesis is responsible for its memory improvement. Using 5-bromo-2' deoxyuridien (BrdU) to birth-date newborn neurons and c-Fos expression to identify dentate gyrus (DG) neurons involved in memory processes, we checked here the effect of ghrelin treatment on adult neurogenesis and cognitive behaviors in mice. We further examined the possible effect of ghrelin on the recruitment of new neurons into the spatial memory traces in intact mice. We found that systemic ghrelin treatment (80MUg/kg, ip injection once daily for 8days) stimulated neurogenesis in the adult hippocampus, but had no effect on spatial memory formation. Consistently, it did not affect the incorporation of newborn neurons into the spatial memory circuits. On the contrary, local infusion of ghrelin (8ng/0.5MUl into CA1 region of the hippocampus) impaired spatial memory formation, but did not affect adult neurogenesis. Our results thus suggested that ghrelin plays distinct roles in modulating adult neurogenesis and the memory acquisition in the hippocampus, the two processes may not be correlated and may be mediated by different mechanisms. PMID- 24211303 TI - The Kvbeta2 subunit of voltage-gated potassium channels is interacting with ProSAP2/Shank3 in the PSD. AB - The postsynaptic density is an electron dense meshwork composed of a variety of molecules facilitating neuronal signal transmission. ProSAP2/Shank3 represents a crucial player at postsynaptic sites, assembling large multimeric platforms and anchoring numerous other molecules, thereby linking the functional synapse with the cytoskeleton. ProSAP2/Shank3 is also implicated in the pathogenesis of numerous diseases, including autism spectrum disorders. KvBeta2 (Kvbeta2) on the other hand serves as a regulatory subunit of voltage-gated potassium channels. Kvbeta2 is located at various sites in the neuron including the axon (binding to Kv1.2), the dendrites (binding to Kv4.2) and the synapse. Binding of Kvbeta2 to either Kv1.2 or Kv4 modulates not only the channel conformation but directs targeting of the channel protein complex to distinct loci within the cell. Thus an interaction between ProSAP2 and Kvbeta2 could have important roles at diverse cellular compartments and moreover during maturation stages. We report here on the direct protein-protein interaction of the postsynaptic density anchoring molecule ProSAP2 and the potassium channel subunit Kvbeta2, initially identified in a yeast-two-hybrid-screen. Furthermore, we characterize this interaction at synapses using primary hippocampal neurons in vitro. PMID- 24211305 TI - [Ruptures in Descemet's membrane due to forceps injuries: appearance clinically and on optical coherence tomography]. PMID- 24211304 TI - Interleukin-1beta enhances neuronal vulnerability to proNGF-mediated apoptosis by increasing surface expression of p75(NTR) and sortillin. AB - Many types of injury such as seizure, ischemia, and oxidative stress cause upregulation of the p75 neurotrophin receptor (p75(NTR)) in brain neurons, where it promotes apoptosis, however the mechanism by which p75(NTR) is regulated under these conditions is not well understood. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) are highly produced under these injury conditions and, in particular, are expressed rapidly in the rat hippocampus after seizure. IL-1beta is known to increase neuronal vulnerability under many conditions, although it does not directly induce neuronal death. Recently, we have shown that these cytokines regulate p75(NTR) induction both in neurons and astrocytes in vitro. Here, we show that IL-1beta infusion into the brain induces p75(NTR) in neurons of the CA1 area of the hippocampus. While IL-1beta induction of p75(NTR) is not sufficient to induce cell death, we demonstrate that IL-1beta primes the neurons by recruiting p75(NTR) and its coreceptor sortilin to the cell surface, making the neurons more vulnerable to subsequent challenge by proNGF. These results suggest a mechanism by which IL-1beta exacerbates neuronal death following injury. PMID- 24211306 TI - [Foveal hypoplasia in an albino]. PMID- 24211307 TI - [Panuveitis associated with papillary carcinoma of the thyroid]. AB - Ocular involvement secondary to thyroid carcinomas is uncommon. Uveal metastasis may occur. More rarely, they can be responsible for paraneoplastic syndromes. We report the case of a 64-year-old woman who presented with a severe bilateral panuveitis with venous vasculitis associated with hyperthyroidism from a multinodular goiter, complicated by papillary carcinoma. Systemic steroid therapy was initiated; ocular symptoms resolved completely after total thyroidectomy. Other causes of panuveitis with venous vasculitis were ruled out. This is the first reported case of panuveitis associated with papillary thyroid carcinoma. The occurrence of the ocular symptoms with hyperthyroidism and their remission after surgery supports the possibility that this association may not be coincidental. A paraneoplastic phenomenon is suspected. PMID- 24211308 TI - [Screening method for angle closure and angle closure glaucoma using scanning laser polarimeter GDxVCC and photodynamic gonioscopy in a darkened room. One-year outcomes of systematic peripheral iridotomy]. AB - INTRODUCTION: Angle closure glaucoma, a recognized major world health issue disproportionately affecting women and Asians, is not often considered in our European populations, normotensive subjects, myopic patients, or subjects with a deep anterior chamber. Early diagnosis is worthwhile, as laser peripheral iridotomy (LPI) is an effective one-step treatment of the causal mechanism. PATIENTS AND METHODS: We have performed a retrospective study of patients who underwent an LPI, the indication for which was based on "photodynamic" gonioscopy in a darkened room showing iridotrabecular contact in darkness. Such photodynamic gonioscopy was motivated by the presence of even minute defects in the nerve fiber layer as seen on the GDxVCC or the presence of a Van Herick sign (narrow limbal anterior chamber depth). RESULTS: One hundred and three eyes of 103 patients underwent LPI and a minimum 1-year follow-up (mean follow-up almost 2 years). Mean age was 63.7+/-11.8 years, and women accounted for 63.1% of cases. The vast majority (78.6%) of patients had neither glaucoma nor ocular hypertension. There were 60.1% hyperopes and 39.9% myopes. Over half (57%) had a deep or a very deep anterior chamber. After LPI, there was immediate deepening of the limbal depth of the anterior chamber in 100% of cases. The aqueous humor that flowed forward was almost always viscous-looking. After 1 year, the IOP was 1.3mm Hg+/-2.4 lower (P<.001) (t test). All patients who had experienced morning headaches (44% of patients) were relieved of this symptom. GDxVCC after 1 year was clearly improved in 18% of cases, slightly improved in 20%, stable in 50%, slightly worse in 11% of cases, and clearly worse in 1%. Cases treated at an earlier stage had a better improvement in GDxVCC. DISCUSSION: Our study shows frequent chronic angle closure in our European population even with deep anterior chambers. Absence of a Van Herick sign does not rule out angle closure at night. A photodynamic gonioscopy with the Goldmann three-lens mirror (to avoid unintentional indentation with the small diameter lenses in these normotensive eyes) should be performed in a darkened room. LPI is an effective one-step treatment of the underlying cause, that is particularly beneficial if performed early. PMID- 24211309 TI - ST-segment elevation myocardial infarction treated by radial or femoral approach in a multicenter randomized clinical trial: the STEMI-RADIAL trial. AB - OBJECTIVES: This study sought to compare radial and femoral approaches in patients presenting with ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PCI) by high-volume operators experienced in both access sites. BACKGROUND: The exact clinical benefit of the radial compared to the femoral approach remains controversial. METHODS: STEMI-RADIAL (ST Elevation Myocardial Infarction treated by RADIAL or femoral approach) was a randomized, multicenter trial. A total of 707 patients referred for STEMI <12 h of symptom onset were randomized in 4 high-volume radial centers. The primary endpoint was the cumulative incidence of major bleeding and vascular access site complications at 30 days. The rate of net adverse clinical events (NACE) was defined as a composite of death, myocardial infarction, stroke, and major bleeding/vascular complications. Access site crossover, contrast volume, duration of intensive care stay, and death at 6 months were secondary endpoints. RESULTS: The primary endpoint occurred in 1.4% of the radial group (n = 348) and 7.2% of the femoral group (n = 359; p = 0.0001). The NACE rate was 4.6% versus 11.0% (p = 0.0028), respectively. Crossover from radial to femoral approach was 3.7%. Intensive care stay (2.5 +/- 1.7 days vs. 3.0 +/- 2.9 days, p = 0.0038) as well as contrast utilization (170 +/- 71 ml vs. 182 +/- 60 ml, p = 0.01) were significantly reduced in the radial group. Mortality in the radial and femoral groups was 2.3% versus 3.1% (p = 0.64) at 30 days and 2.3% versus 3.6% (p = 0.31) at 6 months, respectively. CONCLUSIONS: In patients with STEMI undergoing primary PCI by operators experienced in both access sites, the radial approach was associated with significantly lower incidence of major bleeding and access site complications and superior net clinical benefit. These findings support the use of the radial approach in primary PCI as first choice after proper training. (Trial Comparing Radial and Femoral Approach in Primary Percutaneous Coronary Intervention [PCI] [STEMI-RADIAL]; NCT01136187). PMID- 24211310 TI - Use of fluorescent staining and flow cytometry for monitoring physiological changes in solventogenic clostridia. AB - Physiological changes in populations of Clostridium beijerinckii and Clostridium tetanomorphum were monitored by fluorescence staining and flow cytometry. To estimate the number of metabolically active cells in exponential growth, a combination of the dyes propidium iodide and carboxy fluorescein diacetate appeared to be a good choice for both species. During stationary phase, these stains did not reflect physiological changes sufficiently and therefore additional labeling with bis-(1,3-dibutylbarbituric acid) trimethineoxonol was applied. Results of fluorescence staining in solventogenic batch fermentations were compared with substrate-use data, the concentration of key metabolites and growth curves. We demonstrate that measurements by all methods were mutually compatible. PMID- 24211311 TI - A comparative study of nucleostemin family members in zebrafish reveals specific roles in ribosome biogenesis. AB - Nucleostemin (NS) is an essential protein for the growth and viability of developmental stem cells. Its functions are multi-faceted, including important roles in ribosome biogenesis and in the p53-induced apoptosis pathway. While NS has been well studied, the functions of its family members GNL2 and GNL3-like (GNL3L) remain relatively obscure despite a high degree of sequence and domain homology. Here, we use zebrafish lines carrying mutations in the ns family to compare and contrast their functions in vertebrates. We find the loss of zebrafish ns or gnl2 has a major impact on 60S large ribosomal subunit formation and/or function due to cleavage impairments at distinct sites of pre-rRNA transcript. In both cases this leads to a reduction of total protein synthesis. In contrast, gnl3l loss shows relatively minor rRNA processing delays that ultimately have no appreciable effects on ribosome biogenesis or protein synthesis. However, the loss of gnl3l still results in p53 stabilization, apoptosis, and lethality similarly to ns and gnl2 loss. The depletion of p53 in all three of the mutants led to partial rescues of the morphological phenotypes and surprisingly, a rescue of the 60S subunit collapse in the ns mutants. We show that this rescue is due to an unexpected effect of p53 loss that even in wild type embryos results in an increase of 60S subunits. Our study presents an in depth description of the mechanisms through which ns and gnl2 function in vertebrate ribosome biogenesis and shows that despite the high degree of sequence and domain homology, gnl3l has critical functions in development that are unrelated to the ribosome. PMID- 24211312 TI - Two tarantula venom peptides as potent and differential Na(V) channels blockers. AB - Voltage dependent sodium (Na(V)) channels are large membrane spanning proteins which lie in the basis of action potential generation and propagation in excitable cells and hence are essential mediators of neuronal signaling. Inhibition of Na(V) channel activity is one of the core mechanisms to treat conditions related to neuronal hyperexcitability, such as epilepsy in the clinic. Na(V) channel blockers are also extensively used to locally inhibit action potential generation and related pain perceptions in the form of local anesthetics. Here we describe the isolation, biochemical characterization, synthesis and in vitro characterization of two potent Na(V) channel blockers from the venom of the Paraphysa scrofa (Phrixotrichus auratus) tarantula spider. Both Voltage sensor toxin 3 (VSTx-3, kappa-theraphotoxin-Gr4a) and GTx1-15 (Toxin Gtx1 15), were originally isolated from the venom of the related tarantula Grammostola rosea and described as K(V) and Ca(V) channel blockers, respectively. In our hands, GTx1-15 was shown to be a potent inhibitor of tetrodotoxin (TTX)-sensitive channels (IC50 0.007 MUM for hNa(V)1.7 and 0.12 MUM for hNa(V)1.3 channels), with very little effect on TTX-resistant (Na(V)1.5 and NaV1.8) channels. VSTx-3 was demonstrated to be a potent, TTX-sensitive sodium channel blocker and especially, potent blocker of Na(V)1.8 channels (IC50 0.19 MUM for hNa(V)1.3, 0.43 MUM for hNa(V)1.7 and 0.77 MUM for hNa(V)1.8 channels). Such potent inhibitors with differential selectivity among Na(V) channel isoforms may be used as tools to study the roles of the different channels in processes related to hyperexcitability and as lead compounds to treat pathological pain conditions. PMID- 24211313 TI - Bacillus cereus enterotoxins act as major virulence factors and exhibit distinct cytotoxicity to different human cell lines. AB - A comparative analysis on the relevance of the Bacillus cereus enterotoxins Nhe (nonhemolytic enterotoxin), HBL (haemolysin BL) and CytK (cytotoxin K) was accomplished, concerning their toxic activity towards different target cell lines. Overall, among the components secreted by the reference strains for Nhe and HBL, the enterotoxin complexes accounted for over 90% of the total toxicity. Vero and primary endothelial cells (HUVEC) were highly susceptible to Nhe, whereas Hep-G2, Vero and A549 reacted most sensitive to Nhe plus HBL. For CytK the highest toxicity was observed on CaCo-2 cells. As HBL positive strains always produce Nhe in parallel, the specific contribution of both enterotoxin complexes to the overall observed cytotoxic effects was determined by consecutively removing their single components. While in most cell lines Nhe and HBL contributed more or less equally (40-60%) to cytotoxicity, the relative activity of Nhe was approximately 90% in HUVEC, and that of HBL 75% in A549 cells. With U937, a nearly Nhe resistant cell line was identified for the first time. This distinct susceptibility of cell lines was confirmed by investigating a set of 37 B. cereus strains. Interestingly, whereas Nhe is the enterotoxin mainly responsible for cell death as determined by WST-1 bioassays, more rapid pore formation was observed when HBL was present, pointing to a different mode of action of the two enterotoxin complexes. Furthermore, correlation was observed between cytotoxicity of solely Nhe producing strains and NheB. Cytotoxicity of Nhe/HBL producing isolates correlated with the expression of HBL L1, NheB and HBL B. In conclusion, the observed susceptibilities of target cell lines of different histological origin underline that B. cereus enterotoxins represent major virulence factors and that toxicity is not restricted to gastrointestinal infections. The varying contribution of Nhe and HBL to total cytotoxicity strongly indicates that Nhe as well as HBL specific B. cereus enterotoxin receptors exist. PMID- 24211314 TI - Combined inhibition of Na+ and Ca2+ channels: a novel paradigm for the treatment of incessant ventricular arrhythmias in Andersen-Tawil syndrome. PMID- 24211315 TI - Left atrial thrombus after appendage ligation with LARIAT. PMID- 24211316 TI - Priming of beta-2 agonist and antimuscarinic induced physiological responses induced by 1200mg/day NAC in moderate to severe COPD patients: A pilot study. AB - This study evaluated antioxidant modulations of lung physiological-responses to beta-2-agonist and antimuscarinic bronchodilators with 1200mg/day n-acetyl cysteine (NAC) in a placebo-controlled, randomised, double-blind, parallel-group study, in moderate-very severe COPD patients. METHODS: 15 COPD patients received NAC treatment, while 9 COPD patients received placebo treatment, for 15 days. Pre and-post salbutamol and ipratopium-bromide lung-physiology responses were measured using body-plethysmography, impulse-oscillometry (IOS) and spirometry before-and-after study treatments. RESULTS: Compared to pre-treatment, the NAC treatment significantly enhanced the potential of ipratopium-bromide to reduce functional-residual-capacity (FRC) by nearly 3-folds (mean% FRC-response: pre NAC: -5.51%+/-10.42% versus post-NAC: -17.89%+/-12.94%, p=0.02; mean-absolute FRC response: pre-NAC: -300ml+/-450ml versus post-NAC: -770ml+/-550ml, p=0.02), which was superior to placebo-treatment. The increase in total-lung-capacity response to ipratopium-bromide, although insignificant, was superior with post-NAC treatment versus post-placebo treatment (p=0.049). The salbutamol-response remained unaltered with either treatment. CONCLUSION: The treatment with 1200mg/day NAC has potential to enhance the bronchodilator ability of antimuscarinic-agents but not beta-2-agonist. However, its clinical application has to be established in large sample-size studies for longer-duration. PMID- 24211317 TI - Ventilatory patterns differ between maximal running and cycling. AB - To determine the effect of exercise mode on ventilatory patterns, 22 trained men performed two maximal graded exercise tests; one running on a treadmill and one cycling on an ergometer. Tidal flow-volume (FV) loops were recorded during each minute of exercise with maximal loops measured pre and post exercise. Running resulted in a greater VO2peak than cycling (62.7+/-7.6 vs. 58.1+/-7.2mLkg(-1)min( 1)). Although maximal ventilation (VE) did not differ between modes, ventilatory equivalents for O2 and CO2 were significantly larger during maximal cycling. Arterial oxygen saturation (estimated via ear oximeter) was also greater during maximal cycling, as were end-expiratory (EELV; 3.40+/-0.54 vs. 3.21+/-0.55L) and end-inspiratory lung volumes, (EILV; 6.24+/-0.88 vs. 5.90+/-0.74L). Based on these results we conclude that ventilatory patterns differ as a function of exercise mode and these observed differences are likely due to the differences in posture adopted during exercise in these modes. PMID- 24211318 TI - The cognitive significance of resonating neurons in the cerebral cortex. AB - Most neural fibers of the cerebral cortex engage in electric signaling, but one particular fiber, the apical dendrite of the pyramidal neuron, specializes in electric resonating. This dendrite extends upward from somas of pyramidal neurons, the most numerous neurons of the cortex. The apical dendrite is embedded in a recurrent corticothalamic circuit that induces surges of electric current to move repeatedly down the dendrite. Narrow bandwidths of surge frequency (resonating) enable cortical circuits to use specific carrier frequencies, which isolate the processing of those circuits from other circuits. Resonating greatly enhances the intensity and duration of electrical activity of a neuron over a narrow frequency range, which underlies attention in its various modes. Within the minicolumn, separation of the central resonating circuit from the surrounding signal processing network separates "having" subjective impressions from "thinking about" them. Resonating neurons in the insular cortex apparently underlie cognitive impressions of feelings. PMID- 24211319 TI - Prediction of poor mobilization of autologous CD34+ cells with growth factor in multiple myeloma patients: implications for risk-stratification. AB - It is unknown whether clinical characteristics can successfully predict which multiple myeloma (MM) patients would be poor mobilizers with growth factor (GF) alone so they can be assigned to mobilization with chemotherapy + GF or GF + plerixafor. MM patients (N = 477) who underwent autologous mobilization with GF were retrospectively reviewed and assigned into training and validation cohorts. In multiple regression analysis, age, platelet count at time of mobilization, type of GF utilized, and extent of exposure to lenalidomide independently correlated with peripheral blood (PB)-CD34+ and were integrated in a predicting score (PS) for poor mobilizers, defined as PB-CD34+ < 20/mm(3) 4 days after initiation of GF. There was no correlation between institution, gender, time between diagnosis, and mobilization or plasma cells in the bone marrow at time of mobilization and PBCD34+. The PS cut-off found in the training cohort to have 90% sensitivity for prediction of poor mobilizers performed with 89.7% sensitivity but only 34.8% specificity in the validation cohort. Conversely, the PS cut-off developed to have 90% specificity performed with 86.9% specificity but only 37% sensitivity. We conclude that clinical characteristics identifiable before initiation of mobilization should not be used to stratify MM patients for different mobilization strategies. PMID- 24211320 TI - Testosterone influences song behaviour and social dominance - but independent of prenatal yolk testosterone exposure. AB - In the last two decades, maternally derived yolk androgens have been shown to significantly alter offspring development, and a number of these effects persist into adulthood. However, little is known about their underlying mechanisms. Mechanisms that have been suggested are changes in the endogenous androgen production post-hatching or changes in the sensitivity towards circulating androgens. We tested the effects of yolk testosterone on the plasma testosterone levels and the sensitivity to testosterone in 5months old male canaries that hatched from eggs that were either injected with testosterone (yT-males) or with a control solution (yC-males). Changes in sensitivity were investigated via the behavioural response to an experimental elevation of the plasma testosterone levels. We performed the experiment in fall (low endogenous testosterone production), focusing on testosterone dependent response traits (aggression and song). Before implantation, there was a non-significant trend that the plasma testosterone levels were lower in yT-males than in yC-males. Elevating the plasma testosterone concentrations increased aggressiveness, song bout length and similarity of repeated song elements (=consistency), with the latter likely being a consequence of testosterone-driven song crystallization. However, these effects were not different among yT- or yC-males in any of the parameters. Thus, our findings render it unlikely that changes in the sensitivity to testosterone post hatching would form the main underlying mechanism of hormone-mediated maternal effects in birds. Further experiments are urgently needed in order to understand the nature of the phenotypic effects resulting from embryonic exposure to maternal yolk testosterone. PMID- 24211321 TI - Synthesis and in vitro antiproliferative evaluation of some novel B norcholesterols. AB - Some novel B-norcholesterols with different substituted groups were synthesized. The antiproliferative activity of the compounds against cervical carcinoma (HeLa), liver cancer (Bel 7404) and gastric cancer (SGC 7901) cells was assayed. The results revealed that the presence of a 6-alkylthiosemicarbazone or 6-cyano group could enhance the antiproliferative activity of these compounds. The induction of compounds 6 and 9 to cancer cell apoptosis were assayed by flow cytometry, and the results showed that the compounds were able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer drug. The results suggest that compounds 6 and 9 based on its abeo-cholestane may constitute a novel class of antiproliferative agents, which deserve further study. PMID- 24211322 TI - Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings. AB - OBJECTIVE: Monogenic congenital cataract is one of the most genetically heterogeneous ocular conditions with almost 30 different genes involved in its etiology. In adult patients, genotype-phenotype correlations are troubled by eye surgery during infancy and/or long-term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency as the cause of autosomal recessive congenital cataract in a family from Costa Rica. METHODS: Four affected siblings were included in the study. All of them underwent eye surgery during the first decade but medical records were not available. Congenital cataract was diagnosed by report. Molecular analysis included genome wide homozygosity mapping using a 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene. RESULTS: Genome wide homozygosity mapping revealed a 6Mb region of homozygosity shared by two affected siblings at 17q25. The GALK1 gene was included in this interval and direct sequencing of this gene revealed a homozygous c.1144C>T mutation (p.Q382) in all four affected subjects. CONCLUSIONS: This work demonstrates the utility of homozygosity mapping in the retrospective diagnosis of a family with congenital cataracts in which ocular surgery at early age, the lack of medical records, and the presence of long term eye complications, impeded a clear clinical diagnosis during the initial phases of evaluation. PMID- 24211323 TI - High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: molecular and clinical findings of Turkish probands. AB - Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype-phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829-2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n=12, 46.2% neurological presentation), followed by thromboembolic events (n=6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n=5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%. In addition, five thrombophilic nucleotide changes including MTHFR c.677 C>T and c.1298 A>C, Factor V c.1691 G>A, Factor II c.20210 G>A, and SERPINE1 4G/5G were investigated to assess their contributions to the clinical spectrum. We suggest that the effect of these polymorphisms on clinical phenotype of CBS is not very clear since the distribution of thrombophilic polymorphisms does not differ among specific groups. This study provides molecular findings of 26 Turkish probands with homocystinuria and discusses the clinical presentations and putative effects of the CBS mutations. PMID- 24211324 TI - A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency. AB - Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management. PMID- 24211325 TI - Cloning, characterization, hypoxia and heat shock response of hypoxia inducible factor-1 (HIF-1) from the small abalone Haliotis diversicolor. AB - In this study, hypoxia inducible factor-1alpha (HIF-1alpha) and hypoxia inducible factor-1beta (HIF-1beta) from small abalone Haliotis diversicolor were cloned. The cDNA of H. diversicolor HIF-1alpha (HdHIF-1alpha) is 2,833 bp encoding a protein of 711aa and H. diversicolor HIF-1beta (HdHIF-1beta) is 1919 bp encoding a protein of 590aa. Similar to other species' HIF-1, HdHIF-1 has one basic helix loop-helix (bHLH) domain and two Per-Arnt-Sim (PAS) domains, and HdHIF-1alpha has a oxygen-dependent degradation domain (ODDD) with two proline hydroxylation motifs and a C-terminal transactivation domain (C-TAD) with an asparagine hydroxylation motif. Under normoxic conditions, HdHIF-1alpha and HdHIF-1beta mRNAs were constitutively present in all examined tissues. Under hypoxia (2.0mg/L DO at 25 degrees C) stress, HdHIF-1alpha expression was up-regulated in gills at 4h, 24h and 96 h, and in hemocytes at 24h and 96 h, while HdHIF-1beta remained relatively constant. Under thermal stress (31 degrees C), HdHIF-1alpha expression was significantly increased in gills at 4h, and hemocytes at 0 h and 4 h, while HdHIF-1beta expression still remained relatively constant. These results suggested that HIF-1alpha may play an important role in adaption to poor environment in H. diversicolor. PMID- 24211326 TI - Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells. AB - MicroRNA-449a (miR-449a) was significantly downregulated in 156 lung cancer tissues (p<0.001). We found that the low expression of miR-449a was highly correlated with cancer recurrence and survival of lung cancer patients. The transient introduction of miR-449a caused cell cycle arrest and cell senescence in A549 and 95D cells. Further studies revealed that E2F3 was a direct target of miR-449a in lung cancer cells. miR-449a also suppressed tumor formation in vivo in nude mice. These results suggest that miR-449a plays an important role in lung cancer tumorigenesis and that miR-449a might predict cancer recurrence and survival of lung cancer patients. PMID- 24211327 TI - In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross binding specificity. AB - Signal transducers and activators of transcription (STATs) comprise a family of transcription factors that are structurally related and which participate in signaling pathways activated by cytokines, growth factors and pathogens. Activation of STAT proteins is mediated by the highly conserved Src homology 2 (SH2) domain, which interacts with phosphotyrosine motifs for specific contacts between STATs and receptors and for STAT dimerization. By generating new models for human (h)STAT1, hSTAT2 and hSTAT3 we applied comparative in silico docking to determine SH2-binding specificity of the STAT3 inhibitor stattic, and of fludarabine (STAT1 inhibitor). Thus, we provide evidence that by primarily targeting the highly conserved phosphotyrosine (pY+0) SH2 binding pocket stattic is not a specific hSTAT3 inhibitor, but is equally effective towards hSTAT1 and hSTAT2. This was confirmed in Human Micro-vascular Endothelial Cells (HMECs) in vitro, in which stattic inhibited interferon-alpha-induced phosphorylation of all three STATs. Likewise, fludarabine inhibits both hSTAT1 and hSTAT3 phosphorylation, but not hSTAT2, by competing with the highly conserved pY+0 and pY-X binding sites, which are less well-preserved in hSTAT2. Moreover we observed that in HMECs in vitro fludarabine inhibits cytokine and lipopolysaccharide induced phosphorylation of hSTAT1 and hSTAT3 but does not affect hSTAT2. Finally, multiple sequence alignment of STAT-SH2 domain sequences confirmed high conservation between hSTAT1 and hSTAT3, but not hSTAT2, with respect to stattic and fludarabine binding sites. Together our data offer a molecular basis that explains STAT cross-binding specificity of stattic and fludarabine, thereby questioning the present selection strategies of SH2 domain-based competitive small inhibitors. PMID- 24211328 TI - Fluridone as a new anti-inflammatory drug. AB - Fluridone is a herbicide extensively utilized in agriculture for its documented safety in animals. Fluridone contains a 4(1H)-pyridone and a trifluoromethyl benzene moiety, which are also present in molecules with analgesic and anti inflammatory properties. The established absence of adverse effects of Fluridone on animals prompted us to investigate whether it could represent a new anti inflammatory compound targeting human cells. In stimulated human monocytes, micromolar Fluridone inhibited cyclooxygenase-2 expression and the release of monocyte chemoattractant protein-1 and prostaglandin-E2, to a similar extent as Acetylsalicylic acid. Fluridone also inhibited the proliferation of aortic smooth muscle cells and reduced proliferation and cytokine release by human activated lymphocytes. The mechanism of Fluridone seems to rely on the dose-dependent inhibition of the nuclear translocation of nuclear factor-kappaB, a transcription factor playing a pivotal role in inflammation. Fluridone also inhibited the release from stimulated human monocytes of abscisic acid, a plant stress hormone recently discovered also in mammalian cells, where it stimulates pro-inflammatory responses. Interestingly, the mechanism of Fluridone's toxicity in plants relies on the inhibition of the enzyme phytoene desaturase, involved in the biosynthetic pathway of beta-carotene, the precursor of absciscic acid in plants. Finally, administration of Fluridone reduced peritoneal inflammation in Zymosan-treated mice. These results suggest that Fluridone could represent a new prototype of anti-inflammatory drug, also active on abscisic acid pro-inflammatory pathway. PMID- 24211330 TI - Impact of single nucleotide polymorphisms in the essential HCV entry factor CD81 on HCV infectivity and neutralization. AB - End stage liver disease caused by chronic infection with the hepatitis C virus (HCV) is a leading indication for liver transplantation, yet outcomes are poor since the liver graft is rapidly re-infected by HCV. Antibodies against the essential HCV receptor CD81 have been shown to inhibit HCV cell entry in vitro and in vivo and may represent an attractive treatment option. However, several CD81 variants exist at low levels in human populations. We aimed to investigate to what extent these variants function as HCV receptors and would be amenable to therapeutic interventions with CD81 antibodies. We used lentiviral expression to introduce wildtype or variant CD81 in the CD81(low) Lunet N4 cell line. HCV replication cycle steps and neutralization by CD81 antibodies were then investigated using full length HCV reporter viruses (HCVcc) as well as HCV pseudoparticles (HCVpp). We found that all tested CD81 variants support cell entry by HCVpp and HCVcc with an efficiency similar to wildtype CD81. Other replication cycle steps, namely intracellular RNA replication and release of new particles, were also unaffected by the presence of CD81 variants. Importantly, four neutralizing antibodies directed against the CD81 LEL (5A6, JS81, 1D6 and 1.3.3.22) retained their ability to inhibit HCV infection when wildtype CD81 on target cells was replaced with any of the CD81 variants. These data indicate that CD81 variants that exist in the human population are fully functional as HCV receptors and their presence would not diminish the efficacy of therapeutic regimens that include CD81-antibodies. PMID- 24211329 TI - Sexual dimorphism in rat aortic endothelial function of streptozotocin-induced diabetes: possible involvement of superoxide and nitric oxide production. AB - Little is known of the interactions between diabetes and sex hormones on vascular function. The objectives of this study were to investigate whether there were sex differences in rat aortic endothelial function one week after the induction of streptozotocin (STZ)-diabetes, and to examine the potential roles of superoxide and nitric oxide (NO) in this sex-specific effect. Endothelium-dependent vasodilatation to acetylcholine (ACh) was measured in rat aortic rings before and after treatment with MnTMPyP (25uM), a superoxide dismutase. Contractile responses to phenylephrine (PE) were generated before and after treatment with l NAME (200MUM), a nitric oxide synthase (NOS) inhibitor. The mRNA expression of NADPH oxidase (Nox) and endothelial nitric oxide synthase (eNOS) were also determined. We demonstrated that (1) STZ-diabetes impaired endothelium-dependent vasodilatation to ACh to a greater extent in female than male aortae, (2) inhibition of superoxide enhanced sensitivity to ACh only in diabetic females, and (3) Nox1 and Nox4 mRNA expression were significantly elevated only in aortic tissue of diabetic females. Furthermore, incubation of aortic rings with l-NAME potentiated PE responses in all groups, but aortae from control females showed a greater potentiation of the PE response after NOS inhibition compared with others. STZ-diabetes reduced the extent of PE potentiation after l-NAME and the aortic eNOS mRNA expression in females to the same levels as seen in males. These data suggest that a decrease in NO, resulting from either decreased eNOS or elevated superoxide, may partially contribute to the predisposition of the female aorta to injury early in diabetes. PMID- 24211332 TI - Novel superparamagnetic sanoparticles for trypsin immobilization and the application for efficient proteolysis. AB - Immobilization of trypsin onto the superparamagnetic carboxymethyl chitosan (Fe3O4 (PEG+CM-CTS)) nanoparticles was studied. FTIR and fluorescence spectroscopy data demonstrated that the Fe3O4 (PEG+CM-CTS) nanoparticles were capable of preventing the trypsin unfolding. Due to the large specific surface area and excellent dispersibility, the adsorption equilibrium of trypsin onto the nanoparticles was achieved quickly within 30min. The results of kinetic parameters (Michaelis constant, Km) with regards to the free trypsin (FT) and immobilized trypsin (IT) were 23.1 and 24.1mg/mL separately, implying that IT has less affinity to the BAEE used as the substrate. However, the MALDI-TOF MS analysis indicated that, IT could be used for fast and efficient Bovine Serum Albumin (BSA) digestion under very facile processes, thanks to the easy manipulation of the magnetic nanoparticles (MNs), as well as the greatly reduced digestion time (from 12h to 15min). IT exhibited a sound stability after re-uses for six times, with 76.3% of the initial activity thereof still retained, thus making it more attractive in the application fields. These results are expected to open up a great potential use of such Fe3O4 (PEG+CM-CTS) nanoparticles as a superior nanosupport for trypsin immobilization. PMID- 24211331 TI - Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. AB - We reported that 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG) selected for the L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain of HIV-1 reverse transcriptase (RT). In this study, we have defined the molecular mechanisms of 3'-azido-ddG resistance by performing in-depth biochemical analyses of HIV-1 RT containing mutations L74V, F77L, V106I, L214F, R277K, and K476N (SGS3). The SGS3 HIV-1 RT was from a single genome-derived full-length RT sequence obtained from 3'-azido-ddG resistant HIV-1 selected in vitro. We also analyzed two additional constructs that either lacked the L74V mutation (SGS3-L74V) or the K476N mutation (SGS3-K476N). Pre-steady state kinetic experiments revealed that the L74V mutation allows RT to effectively discriminate between the natural nucleotide (dGTP) and 3'-azido-ddG triphosphate (3'-azido-ddGTP). 3'-azido-ddGTP discrimination was primarily driven by a decrease in 3'-azido-ddGTP binding affinity (Kd) and not by a decreased rate of incorporation (kpol). The L74V mutation was found to severely impair RT's ability to excise the chain-terminating 3'-azido-ddG-monophosphate (3'-azido ddGMP) moiety. However, the K476N mutation partially restored the enzyme's ability to excise 3'-azido-ddGMP on an RNA/DNA, but not on a DNA/DNA, template/primer by selectively decreasing the frequency of secondary RNase H cleavage events. Collectively, these data provide strong additional evidence that the nucleoside base structure is major determinant of HIV-1 resistance to the 3' azido-2',3'-dideoxynucleosides. PMID- 24211333 TI - Activity-guided identification of acetogenins as novel lipophilic antioxidants present in avocado pulp (Persea americana). AB - Avocado fruit is a rich source of health-related lipophilic phytochemicals such as monounsaturated fatty acids, tocopherols, carotenes, acetogenins and sterols. However, limited information is available on the contribution of specific phytochemicals to the overall antioxidant capacity (AOC) of the fruit. Centrifugal partition chromatography was used as fractionation tool, guided by an in vitro chemical assay of oxygen radical absorbance capacity (ORAC). Subsequent experiments focused on isolation and characterization of the chemical nature of the main contributors to lipophilic AOC of avocado pulp. ORAC values obtained for acetogenins were contrasted with results from an isolated kidney mitochondria membrane lipid peroxidation bioassay. The present study established that lipophilic AOC of the pulp was significantly higher than its hydrophilic AOC. Our results confirmed the presence of acetogenins in the fractions with highest lipophilic AOC, and for the first time linked them as contributors to lipophilic ORAC values. Further HPLC-PDA/MS-TOF analysis led to structural elucidation of two novel acetogenins, not previously reported as present in avocado pulp, along with five already known related-compounds. Antioxidant properties observed for avocado pulp acetogenins by the ORAC assay suggested that, in the presence of an emulsifying agent, acetogenins could serve as novel lipophilic antioxidants in a food matrix. Results from isolated mitochondria lipid peroxidation bioassay, indicated that L-ORAC values which may have relevance for food matrix applications, should not be interpreted to have a direct relevance in health related claims, compounds need to be evaluated considering the complexity of biological systems. PMID- 24211335 TI - Characterization of copper transport in gill cells of a mangrove crab Ucides cordatus. AB - The branchial epithelium of crustaceans is exposed to the environment and is the first site affected by metal pollution. The aim of this work was to characterize copper (Cu) transport using a fluorescent dye, Phen Green, in gill cells of a hypo-hyper-regulator mangrove crab Ucides cordatus. The results showed that added extracellular CuCl2 (0, 0.025, 0.150, 0.275, 0.550 and 1.110 MUM) showed typical Michaelis-Menten transport for Cu in anterior and posterior gill cells (Vmax for anterior and posterior gills: 0.41 +/- 0.12 and 1.76 +/- 0.27 intracellular Cu in MUM * 22.10(4)cells(-1)* 300 s(-1) respectively and Km values: 0.44 +/- 0.04 and 0.32 +/- 0.13 MUM, respectively). Intracellular Cu was significantly higher for posterior gill cells compared to anterior gill cells, suggesting differential accumulation for each gill type. Extracellular Ca at 20mM decreased cellular Cu transport for both anterior and posterior gill cells. Nifedipine and verapamil, calcium channel inhibitors from plasma membrane, decreased Cu transport and affected Km for both gills. These results could be due to a competition between Cu and Ca. Amiloride, a Na/Ca exchanger inhibitor, as well as bafilomycin, a proton pump inhibitor, caused a decrease of intracellular Cu compared to control. Ouabain and KB-R 7943, acting on Na homeostasis, similarly decreased intracellular Cu in both gill cells. Besides that, gill cells exposed to ATP and Cu simultaneously, showed an increase in intracellular copper, which was inhibited by vanadate, an inhibitor of P-type ATPase. These results suggest either the presence of a Cu-ATPase in crab gill cells, responsible for Cu influx, or the effect of a change in electrochemical membrane potential that could also drive Cu to the gill cell interior. Caffeine increased intracellular Cu, suggesting that intracellular Ca could be affecting Cu uptake. Overall the results show that copper uptake in gill cells of crabs is regulated by intracellular Ca, Ca channels and by Na exchangers. This is the first report of Cu transport characterization in whole gill cells of crabs. PMID- 24211334 TI - A new alternative method for testing skin irritation using a human skin model: a pilot study. AB - BACKGROUND: Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin(r), Epiderm(r)). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm(r)). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. OBJECTIVES: To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). METHODOLOGY: Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1 bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). RESULTS: We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). CONCLUSIONS: This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility. PMID- 24211336 TI - Impact of benzo(a)pyrene, Cu and their mixture on the proteomic response of Mytilus galloprovincialis. AB - In natural waters, chemical interactions between mixtures of contaminants can result in potential synergistic and/or antagonic effects in aquatic animals. Benzo(a)pyrene (BaP) and copper (Cu) are two widespread environmental contaminants with known toxicity towards mussels Mytilus spp. The effects of the individual and the interaction of BaP and Cu exposures were assessed in mussels Mytilus galloprovincialis using proteomic analysis. Mussels were exposed to BaP [10 MUg L(-1) (0.396 MUM)], and Cu [10 MUg L(-1) (0.16 MUM)], as well as to their binary mixture (mixture) for a period of 7 days. Proteomic analysis showed different protein expression profiles associated to each selected contaminant condition. A non-additive combined effect was observed in mixture in terms of new and suppressed proteins. Proteins more drastically altered (new, suppressed and 2 fold differentially expressed) were excised and analyzed by mass spectrometry, and eighteen putatively identified. Protein identification demonstrated the different accumulation, metabolism and chemical interactions of BaP, Cu and their mixture, resulting in different modes of action. Proteins associated with adhesion and motility (catchin, twitchin and twitchin-like protein), cytoskeleton and cell structure (alpha-tubulin and actin), stress response (heat shock cognate 71, heat shock protein 70, putative C1q domain containing protein), transcription regulation (zinc-finger BED domain-containing and nuclear receptor subfamily 1G) and energy metabolism (ATP synthase F0 subunit 6 protein and mannose-6-phosphate isomerase) were assigned to all three conditions. Cu exposure alone altered proteins associated with oxidative stress (glutathione-S-transferase) and digestion, growth and remodelling processes (chitin synthase), while the mixture affected only one protein (major vault protein) possibly related to multi drug resistance. Overall, new candidate biomarkers, namely zinc-finger BED domain containing protein, chitin synthase and major vault protein, were also identified for BaP, Cu and mixture, respectively. PMID- 24211337 TI - Application of a hemolysis assay for analysis of complement activation by perfluorocarbon nanoparticles. AB - Nanoparticles offer new options for medical diagnosis and therapeutics with their capacity to specifically target cells and tissues with imaging agents and/or drug payloads. The unique physical aspects of nanoparticles present new challenges for this promising technology. Studies indicate that nanoparticles often elicit moderate to severe complement activation. Using human in vitro assays that corroborated the mouse in vivo results we previously presented mechanistic studies that define the pathway and key components involved in modulating complement interactions with several gadolinium-functionalized perfluorocarbon nanoparticles (PFOB). Here we employ a modified in vitro hemolysis-based assay developed in conjunction with the mouse in vivo model to broaden our analysis to include PFOBs of varying size, charge and surface chemistry and examine the variations in nanoparticle-mediated complement activity between individuals. This approach may provide the tools for an in-depth structure-activity relationship study that will guide the eventual development of biocompatible nanoparticles. FROM THE CLINICAL EDITOR: Unique physical aspects of nanoparticles may lead to moderate to severe complement activation in vivo, which represents a challenge to clinical applicability. In order to guide the eventual development of biocompatible nanoparticles, this team of authors report a modified in vitro hemolysis-based assay developed in conjunction with their previously presented mouse model to enable in-depth structure-activity relationship studies. PMID- 24211338 TI - Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy. AB - There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. PMID- 24211339 TI - Attention bias modification for reducing speech anxiety. AB - The mechanisms mediating the anxiolytic effects of attention bias modification (ABM) remain unclear. Accordingly, we randomly assigned speech-anxious subjects to receive four sessions of one of three training conditions: ABM, inverse ABM, and control. In the ABM condition, subjects viewed pairs of photographs of models displaying facial expressions of disgust and joy on a computer screen. Probes always replaced the positive face, and subjects pushed a button to indicate the identity of the probe (E or F) as rapidly as possible. In the inverse condition, the probes always replaced the negative face, and in the control condition, the probes replaced each face type equally often. After four training sessions, all groups exhibited statistically indistinguishable, but significant, reductions on self-report, behavioral, and physiological measures of speech anxiety. Self report and behavioral measures of attentional control improved likewise. Contrary to early studies, ABM was not superior to control procedures in producing reductions on measures of social anxiety. PMID- 24211340 TI - EcVig, a novel grouper immune-gene associated with antiviral activity against NNV infection. AB - VHSV-induced genes (VIGs) were first identified in rainbow trout (Oncorhynchus mykiss) and subsequently isolated in a variety of fish. Recent studies have shown that most VIGs have immunological functions against pathogenic infections. However, most research has focused on Vig1, such that our present understanding of these genes in other fish species remains limited. This study isolated a homologue of the uncharacterized O. mykiss Vig-B319 (EcVig) from orange-spotted grouper (Epinephelus coioides). Genomic organization suggests that four EcVig isoforms (EcVig A-D), are generated through alternative splicing. Due to the encoding of 2 immunoglobulin (Ig) domains, the EcVig protein can be considered a member of the immunoglobulin superfamily. The expression of EcVig increased 3 days after hatching (dph) and peaked at 9 dph. This pattern is similar to that displayed by EcMx, an important grouper antiviral gene. Additionally, a tissue tropism assay revealed that EcVig A is the major EcVig isoform present in the tissues considered by this study, with the expression of EcVig A exceeding that of EcVig B. We subsequently investigated whether EcVig expression was induced by the viral pathogen nervous necrosis virus (NNV) or the bacterial pathogen Vibrio anguillarum. Following injection with NNV, the expression levels of EcVig showed significant up-regulation. Conversely, a significant reduction was observed in EcVig expression in brain samples collected from V. anguillarum injected grouper. The overexpression of EcVig A suppressed the replication of NNV in grouper GF-1 cell lines, suggesting that EcVig is an important antiviral factor in the grouper immune responses. PMID- 24211341 TI - Identification, characterization and functional analysis of a serine protease inhibitor (Lvserpin) from the Pacific white shrimp, Litopenaeus vannamei. AB - As important arthropod immune responses, prophenoloxidase (proPO) activation and Toll pathway initiation are mediated by serine proteinase cascades and regulated by serpins. Herein, a serine protease inhibitor (Lvserpin), encoding for 415 amino acids with calculated molecular weight of 46,639 Da and isoelectric point of 7.03 was characterized from the Pacific white shrimp Litopenaeus vannamei. Multiple sequence alignment revealed that Lvserpin shared the highest similarity with Penaeus monodon serpin6 (87%). Quantitative real-time PCR (qRT-PCR) results showed that the transcripts of Lvserpin were detected in all the examined tissues and most highly expressed in gill. The expression profiles of Lvserpin were greatly fluctuated upon infection of Vibrio anguillarum, Micrococcus lysoleikticus or White Spot Syndrome Virus (WSSV). Double stranded RNA-mediated suppression of Lvserpin resulted in a significant increase in the transcripts of two clip-domain serine proteinases (PPAE and PPAF), prophenoloxidase (proPO), anti-lipopolysaccharide factor (ALF), Crustin and penaeidin3 (Pens3) and also increased the high cumulative mortality post V. anguillarum injection. Besides, the recombinant Lvserpin protein (rLvserpin) was purified and exhibited inhibitory activity against trypsin. Also the rLvserpin showed inhibition on prophenoloxidase activation and bacterial growth. Hence, we proposed that the Lvserpin played important role in the shrimp innate immunity. PMID- 24211342 TI - A trace ratio maximization approach to multiple kernel-based dimensionality reduction. AB - Most dimensionality reduction techniques are based on one metric or one kernel, hence it is necessary to select an appropriate kernel for kernel-based dimensionality reduction. Multiple kernel learning for dimensionality reduction (MKL-DR) has been recently proposed to learn a kernel from a set of base kernels which are seen as different descriptions of data. As MKL-DR does not involve regularization, it might be ill-posed under some conditions and consequently its applications are hindered. This paper proposes a multiple kernel learning framework for dimensionality reduction based on regularized trace ratio, termed as MKL-TR. Our method aims at learning a transformation into a space of lower dimension and a corresponding kernel from the given base kernels among which some may not be suitable for the given data. The solutions for the proposed framework can be found based on trace ratio maximization. The experimental results demonstrate its effectiveness in benchmark datasets, which include text, image and sound datasets, for supervised, unsupervised as well as semi-supervised settings. PMID- 24211343 TI - A tumoral acidic pH-responsive drug delivery system based on a novel photosensitizer (fullerene) for in vitro and in vivo chemo-photodynamic therapy. AB - Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60-PEI-DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60 PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60 PEI-DOX showed a strong dependence on the environmental pH value. The biodistributions of C60-PEI-DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60-PEI-DOX/Qds) into tumor-bearing mice. C60-PEI-DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60-PEI-DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60-PEI-DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60-PEI-DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60-PEI-DOX may be promising for high treatment efficacy with minimal side effects in future therapy. PMID- 24211344 TI - Polyelectrolyte effects in G-quadruplexes. AB - The role of counterion condensation as a dominant force governing the stability of DNA duplexes and triplexes is well established. In contrast, the effect of counterion condensation on the stability of G-quadrupex conformations is poorly understood. Unlike other ordered nucleic acid structures, G-quadruplexes exhibit a specific binding of counterions (typically, Na(+) or K(+)) which are buried inside the central cavity and coordinated to the O6 carbonyls of the guanines forming the G-quartets. While it has been known that the G-quadruplex-to-coil transition temperature, TM, increases with an increase in the concentration of the stabilizing ion, the contributions of the specific (coordination in the central cavity) and nonspecific (condensation) ion binding have not been resolved. In this work, we separate the two contributions by studying the change in TM of preformed G-quadruplexes following the addition of nonstabilizing ions Li(+), Cs(+), and TMA(+) (tetramethylammonium). In our studies, we used two G quadruplexes formed by the human telomeric sequences which are distinct with respect to the folding topology and the identity and the number of sequestered stabilizing ions. Our data suggest that the predominant ionic contribution to G quadruplex stability comes from the specifically bound Na(+) or K(+) ions and not from counterion condensation. We offer molecular rationalizations to the observed insensitivity of G-quadruplex stability to counterion condensation and emphasize the need to expand such studies to assess the generality of our findings. PMID- 24211345 TI - Inhibition of nitric oxide is a good therapeutic target for bladder tumors that express iNOS. AB - Bladder cancer is the second cause of death for urological tumors in man. When the tumor is nonmuscle invasive, transurethral resection is curative. On the other hand, radical cystectomy is the treatment chosen for patients with invasive tumors, but still under treatment, these patients have high risk of dying, by the development of metastatic disease within 5 years. It is therefore important to identify a new therapeutic target to avoid tumor recurrences and tumor progression. Nitric oxide (NO) is an important biological messenger known to influence several types of cancers. In bladder cancer, production of NO and expression and activity of inducible NO synthase was associated to recurrence and progression. The objective of this work was to analyze if inhibition of nitric oxide production could be considered a therapeutic target for bladder tumors expressing iNOS. Using a bladder cancer murine model with different invasiveness grade we have demonstrated that NO inhibition was able to inhibit growth of bladder tumors expressing iNOS. Furthermore, invasive properties of MB49-I orthotopic growth was inhibited using NO inhibitors. This paper also shows that levels of NO in urine can be correlated with tumor size. In conclusion, inhibition of NO could be considered as a therapeutic target that prevents tumor growth and progression. Also, urine NO levels may be useful for measuring tumor growth. PMID- 24211346 TI - Ammonia and odour emissions from UK pig farms and nitrogen leaching from outdoor pig production. A review. AB - We reviewed specific literature for emissions of ammonia (NH3) and odours from all stages of pig production together with nitrogen (N) leaching from raising pigs outdoors. Emissions of NH3 decrease with decreases in the crude protein (CP) content of pig diets, at all stages of manure management. The CPs of pig diets have been greatly reduced by matching the CP content to the protein required at each stage of the animals' growth and by using synthetic essential amino acids to minimise total CP intake. The CP contents of the dietary ingredients needed to provide energy for the animals impose further limits to reductions in dietary CP. Housing systems have been designed and evaluated which offer potential for reducing NH3 emissions. However such designs may not be applicable at all stages of the pigs' development and the careful management needed to ensure their effective working may be costly and difficult to implement on commercial farms. The factors behind odour emissions are less well characterised. Reducing diet CP to 160 g CP kg(-1) has been shown to reduce odour emissions but further CP reductions may increase them. Some reductions in odour emissions from buildings can be achieved by careful management of the ventilation rate but the most effective measures to reduce emissions of NH3 and odours are to cover slurry stores and to inject slurry into soil. Changes in the feeding and management of outdoor pigs mean that N leaching losses may be up to 50% less than previously reported. No studies have been undertaken that compare the N leached from pigs raised outdoors, versus that arising from the application of pig manure from an equal number of housed pigs. As a precursor to any field study, current models could be used to provide a first estimate of any systematic differences. PMID- 24211347 TI - Anguilliform fish reveal large scale contamination by mine trace elements in the coral reefs of New Caledonia. AB - Due to intensive mining activity, increasing urbanization and industrialization, vast amounts of contaminants are discharged into the lagoon of New Caledonia, one of the largest continuous coral reef systems and a major biodiversity hotspot. The levels of 11 trace element concentrations were examined in the muscles of predator fish in the south-western lagoon (moray eels and congers). These species are sedentary, widespread, abundant, and they are easily collected using a sea snake sampling technique. We found the highest mean and maximal concentrations of different trace elements ever found in coral fish, notably regarding trace elements typical from mining activity (e.g., mean values for Cr and Ni, respectively: 5.53 +/- 6.99 MUg g(-1) [max, 35.7 MUg g(-1)] and 2.84 +/- 3.38 MUg g(-1) [max, 18.0 MUg g(-1)]). Results show that important trace element contamination extends throughout the lagoon to the barrier reef, following a concentration gradient from the oldest nickel factory (Noumea). PMID- 24211348 TI - An integrated material metabolism model for stocks of urban road system in Beijing, China. AB - Rapid urbanization has greatly altered the urban metabolism of material and energy. As a significant part of the infrastructure, urban roads are being rapidly developed worldwide. Quantitative analysis of metabolic processes on urban road systems, especially the scale, composition and spatial distribution of their stocks, could help to assess the resource appropriation and potential environmental impacts, as well as improve urban metabolism models. In this paper, an integrated model, which covered all types of roads, intersection structures and ancillary facilities, was built for calculating the material stocks of urban road systems. Based on a bottom-up method, the total stocks were disassembled into a number of stock parts rather than obtained by input-output data, which provided an approach promoting data availability and inner structure understanding. The combination with GIS enabled the model to tackle the complex structures of road networks and avoid double counting. In the case study of Beijing, the following results are shown: 1) The total stocks for the entire road system reached 159 million tons, of which nearly 80% was stored in roads, and 20% in ancillary facilities. 2) Macadam was the largest stock (111 million tons), while stone mastic asphalt, polyurethane plastics, and atactic polypropylene accounted for smaller components of the overall system. 3) The stock per unit area of pedestrian overcrossing was higher than that of the other stock units in the entire system, and its steel stocks reached 0.49 t/m(2), which was 10 times as high as that in interchanges. 4) The high stock areas were mainly distributed in ring-shaped and radial expressways, as well as in major interchanges. 5) Expressways and arterials were excessively emphasized, while minor roads were relatively ignored. However, the variation of cross-sectional thickness in branches and neighborhood roads will have a significant impact on the scale of material stocks in the entire road system. PMID- 24211349 TI - Nitrogen deposition along differently exposed slopes in the Bavarian Alps. AB - The Alps are affected by high nitrogen deposition, particularly in the fringe of the Northern and Southern Alps. In the framework of a two-year monitoring study performed in 2010 and 2011, we investigated the ammonia and nitrogen dioxide air concentration and ammonium and nitrate deposition at different altitudes between 700 and 1,600 ma.s.l. in the Garmisch-Partenkirchen district in the Upper Bavaria region (Germany). Four-weekly measurements of deposition collected with bulk open field samplers and under-crown were performed in a profile perpendicular to the axis of the Loisach valley; measurements were conducted at eight sites. Whereas open field deposition ranged from 5 to 11 kg ha(-1)a(-1), nitrogen throughfall has reached up to 21 kg ha(-1)a(-1). Data from the valley and the slopes were compared with measurements performed on the platform of the Environmental Research Station Schneefernerhaus (Zugspitze) at an altitude of 2,650 ma.s.l. For the rough estimation of the total yearly deposition rate of nitrogen, the canopy uptake model was applied. By regarding nitrogen uptake by the trees, total deposition can exceed the throughfall in all sites by up to 50%. Additionally, we estimated the total deposition from the sum of wet and dry deposition. On the one side, the wet deposition could be extrapolated from the open field deposition. On the other side, we used the inferential method to calculate the dry deposition on the basis of NH3 and NO2 air concentrations and their literature based deposition velocities. Since fixed deposition velocities are inappropriate particularly in complex orography, we tried to find correction factors based upon terrain characteristics and meteorological considerations. Temperature monitoring at the eight sites and wind measurements at two sites provided some evidence for the semi-empirical parameterization. Due to numerous imponderabilities, the results of the two methods were not consistent for all sites. PMID- 24211350 TI - Design, synthesis and biological evaluation of paclitaxel-mimics possessing only the oxetane D-ring and side chain structures. AB - Two spiro paclitaxel-mimics consisting only of an oxetane D-ring and a C-13 side chain were designed and synthesized on the basis of analysis of structure activity relationships (SAR) of paclitaxel. In vitro microtubule-stabilizing and antiproliferative assays indicated a moderate weaker activity of the mimics than paclitaxel, but which still represented the first example of simplified paclitaxel analogues with significant anti-tumor biological activity. PMID- 24211351 TI - Lack of anti-androgenic effects of equol on reproductive neuroendocrine function in the adult male rat. AB - Equol (EQ), a metabolite of the soy isoflavone daidzein, has well known estrogenic properties. Data from animal studies suggested that EQ may act also as an anti-androgen. However, data regarding how EQ may affect brain functions like the regulation of neuroendocrine activity and reproductive outcomes in adult male rats are still lacking. We therefore investigated the effects of EQ on sex steroid regulated gene expression in the brain [medial preoptic area/anterior hypothalamus (MPOA/AH) and medial basal hypothalamus/median eminence (MBH/ME)], pituitary, and prostate as a reference androgen-dependent organ. Furthermore reproductive outcomes were evaluated. The anti-androgen flutamide (FLUT) served as reference compound. Male rats (n=12 per group) were treated by gavage for 5 days with either EQ (100 or 250 mg/kgBW/day), or FLUT 100 mg/kgBW/day. All vehicle- and EQ-treated males showed successful reproductive outcomes, whereas FLUT-exposed males had severe reproductive impairments resulted in infertility. FLUT decreased relative weights of prostate, seminal vesicles and epididymides, and increased serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone and 5alpha-dihydrotestosterone without altering prolactin levels, whereas EQ exerted opposite effects. Both EQ and FLUT decreased gonadotropin releasing hormone (GnRH) expression in the MPOA/AH. Only FLUT upregulated levels of GnRH receptor expression both in the MBH/ME and pituitary. While EQ downregulated the hypothalamic ERalpha and ERbeta expressions, but FLUT did not. In the prostate, only FLUT upregulated both ERalpha and AR mRNA expression levels. Taken together, our findings are the first data that EQ did not induce anti-androgenic effects on brain, prostate and male reproductive parameters, however, estrogenic neuroendocrine and reproductive effects of EQ were observed. PMID- 24211353 TI - The role of angular reflection in assessing elastic properties of bone by scanning acoustic microscopy. AB - For an assessment of the mechanical performance of bone, a quantitative description of its mechanical heterogeneity is necessary. Previously, scanning acoustic microscopy (SAM) was used as a non-destructive method to estimate bone stiffness on the micrometer scale. While up to now only the normal incidence of acoustic waves is taken into account, we extend in our study the evaluation procedure by considering the full opening of the acoustic lens. The importance of this technical aspect is demonstrated by determining the contrast in Young's modulus between newly formed osteons and the surrounding higher mineralized interstitial bone. Several regions of human cortical bone of a femur in cross section were imaged. For all the regions quantitative backscattered-electron imaging (qBEI) to estimate the local mass density was combined with SAM measurements. These measurements reveal a non-monotonic dependence between acoustic reflectivity and Young's modulus, which shows that it is actually necessary to consider the lens opening in a quantitative way. This problem was experimentally and theoretically approached by using lenses with two different opening angles operated at different frequencies (52 degrees at 400MHz and 80 degrees at 820MHz) to image the same specimen. The mass density of bone in osteons was found to be 1930kg/m(3) on average, while the higher mineral content in interstitial bone results in a 9% increase of the density. The contrast in the effective Young's modulus E, as determined through SAM, is more pronounced, with an average value of 14GPa in osteons and a more than 60% increase in interstitial bone. Additionally, SAM maps show oscillations in E with a periodicity of the typical bone lamella thickness of approximately 7um in both osteons and interstitial bone. This mechanical heterogeneity can be explained by the varying orientation of the mineralized collagen fibers. PMID- 24211352 TI - Role of the EphB2 receptor in autophagy, apoptosis and invasion in human breast cancer cells. AB - The Eph and Ephrin proteins, which constitute the largest family of receptor tyrosine kinases, are involved in normal tissue development and cancer progression. Here, we examined the expression and role of the B-type Eph receptor EphB2 in breast cancers. By immunohistochemistry using a progression tissue microarray of human clinical samples, we found EphB2 to be expressed in benign tissues, but strongly increased in cancers particularly in invasive and metastatic carcinomas. Subsequently, we found evidence that EphB2, whose expression varies in established cell breast lines, possesses multiple functions. First, the use of a DOX-inducible system to restore EphB2 function to low expressers resulted in decreased tumor growth in vitro and in vivo, while its siRNA-mediated silencing in high expressers increased growth. This function involves the onset of apoptotic death paralleled by caspases 3 and 9 activation. Second, EphB2 was also found to induce autophagy, as assessed by immunofluorescence and/or immunoblotting examination of the LC3, ATG5 and ATG12 markers. Third, EphB2 also has a pro-invasive function in breast cancer cells that involves the regulation of MMP2 and MMP9 metalloproteases and can be blocked by treatment with respective neutralizing antibodies. Furthermore, EphB2-induced invasion is kinase-dependent and is impeded in cells expressing a kinase-dead mutant EphB2. In summary, we identified a mechanism involving a triple role for EphB2 in breast cancer progression, whereby it regulates apoptosis, autophagy, and invasion. PMID- 24211354 TI - Modification of acrylic bone cement with mesoporous silica nanoparticles: effects on mechanical, fatigue and absorption properties. AB - Polymethyl methacrylate bone cement is the most common and successful method used to anchor orthopedic implants to bone, as evidenced by data from long-term national joint registries. Despite these successes, mechanical failure of the cement mantle can result in premature failure of an implant which has lead to the development of a variety of techniques aimed at enhancing the mechanical properties of the cement, such as the addition of particulate or fiber reinforcements. This technique however has not transitioned into clinical practice, likely due to problems relating to interfacial particle/matrix adhesion and high cement stiffness. Mesoporous silica nanoparticles (MSNs) are a class of materials that have received little attention as polymer reinforcements despite their potential ability to overcome these challenges. Therefore, the objective of the present study was to investigate the use of mesoporous silica nanoparticles (MSNs) as a reinforcement material within acrylic bone cement. Three different MSN loading ratios (0.5%, 2% and 5% (wt/wt)) were incorporated into a commercially available bone cement and the resulting impact on the cement's static mechanical properties, fatigue life and absorption/elution properties were quantified. The flexural modulus and compressive strength and modulus tended to increase with higher MSN concentration. Conversely, the flexural strength, fracture toughness and work to fracture all significantly decreased with increasing MSN content. The fatigue properties were found to be highly influenced by MSNs, with substantial detrimental effects seen with high MSN loadings. The incorporation of 5% MSNs significantly increased cement's hydration degree and elution percentage. The obtained results suggest that the interfacial adhesion strength between the nanoparticles and the polymer matrix was poor, leading to a decrease in the flexural and fatigue properties, or that adequate dispersion of the MSNs was not achieved. These findings could potentially be mitigated in future work by chemically modifying the mesoporous silica with functional groups. PMID- 24211355 TI - Parametric elastic analysis of coupled helical coils for tubular implant applications: experimental characterization and numerical analysis. AB - Coupled helical coils show promising mechanical behavior to be used as tubular organ constructs, e.g., in trachea or urethra. They are potentially easy to manufacture by filament winding of biocompatible and resorbable polymers, and could be tailored for suitable mechanical properties. In this study, coupled helical coils were manufactured by filament winding of melt-extruded polycaprolactone, which was reported to demonstrate desired in vivo degradation speed matching tissue regeneration rate. The tensile and bending stiffness was characterized for a set of couple helical coils with different geometric designs, with right-handed and left-handed polymer helices fused together in joints where the filaments cross. The Young's modulus of unidirectional polycaprolactone filaments was characterized, and used as input together with the structural parameters of the coupled coils in finite element simulations of tensile loading and three-point bending of the coils. A favorable comparison of the numerical and experimental results was found, which paves way for use of the proposed numerical approach in stiffness design under reversible elastic conditions of filament wound tubular constructs. PMID- 24211356 TI - Characterization of load dependent creep behavior in medically relevant absorbable polymers. AB - While synthetic absorbable polymers have a substantial history of use in medical devices, their use is expanding and becoming more prevalent for devices where long term loading and structural support is required. In addition, there is evidence that current absorbable medical devices may experience permanent deformations, warping (out of plane twisting), and geometric changes in vivo. For clinical indications with long term loading or structural support requirements, understanding the material's viscoelastic properties becomes increasingly important whereas these properties have not been used historically as preclinical indications of performance or design considerations. In this study we measured the static creep, creep recovery and cyclic creep responses of common medically relevant absorbable materials (i.e., poly(l-lactide, PLLA) and poly(l-co glycolide, PLGA) over a range of physiologically relevant loading magnitudes. The results indicate that both PLLA and PLGA exhibit creep behavior and failure at loads significantly less than the yield or ultimate properties of the material and that significant material specific responses to loading exist. In addition, we identified a strong correlation between the extent of creep in the material and its crystallinity. Results of the study provide new information on the creep behavior of PLLA and PLGA and support the use of viscoelastic properties of absorbable polymers as part of the material selection process. PMID- 24211357 TI - Poly(gamma-benzyl-L-glutamate)-PEG-alendronate multivalent nanoparticles for bone targeting. AB - Hydroxyapatite (HAP), a highly specific component of bone tissue, is the main target in order to impart osteotropicity. Bone targeted nanoparticles can increase the strength of the interaction with HAP through multivalency and thus constitute a valuable strategy in the therapeutics of skeletal diseases. PBLG10k b-PEG6k-alendronate nanoparticles (~ 75 nm) were prepared by a simple nanoprecipitation method. The calcium affinity (KCa(+2)=1.8 * 10(4)M(-1)) of these nanoparticles was evaluated using isothermal titration calorimetry. The multivalent interaction with HAP surfaces (KHAP) was studied by fluorescence and was estimated to be 1.1 * 10(10)M(-1), which is more than 4000 times stronger than the reported monovalent interaction between alendronate and HAP surfaces. Molecular modeling suggests that the number of binding sites available at the HAP surface is in large excess than what is required for the whole surface coverage by alendronate decorated nanoparticles. The lower calcium affinity of these nanoparticles than for HAP allows calcium bound nanoparticles to interact with HAP, which yields a deeper understanding of bone targeted carriers and could potentially improve their bone targeting properties. PMID- 24211358 TI - Modification of quaternary polymethacrylate films using sodium alginate: film characterization and drug permeability. AB - The aims of this study were to investigate the molecular interaction of quaternary polymethacrylate (QPM) in aqueous-dispersion form with sodium alginate (SA) and to characterize the physicochemical properties, mechanical properties, and drug permeability of the QPM-SA films. The results demonstrated that QPM can interact with SA via electrostatic force, leading to the formation of flocculate particles in the dispersions. Transparent QPM-SA films were prepared using a casting/solvent evaporation method. The positively charged quaternary ammonium groups of QPM can interact with the negatively charged carboxyl groups of SA, which was observed using ATR-FTIR spectroscopy. This interaction caused a change of thermal properties, an increase in film strength, and a decrease in film tackiness. The puncture strength of the wet films in acidic media increased as the amount of SA was increased, but the flexibility of the films decreased. The wet films still presented good strength and flexibility in neutral pH when using 2.5-6.3%w/w SA because of their lower water uptake in such media. The incorporation of SA into QPM films was able to reduce drug permeability but increase drug diffusivity in acidic media. In contrast, the drug diffusivity decreased with the addition of a small amount of SA into the films when using a neutral medium. This phenomenon can be attributed to the effect of pH on the water uptake of the film and the ionization of the SA in the microenvironment of the films. These findings suggest that SA can modify the characteristics of QPM films, and QPM-SA films present a strong potential for application as a film coating material for modified-release tablets. PMID- 24211359 TI - Four new polymorphic forms of suplatast tosilate. AB - We found four new polymorphic forms (gamma-, epsilon-, zeta-, and eta-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (alpha-, beta-, and delta-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the epsilon- and eta-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the epsilon- and eta-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The alpha-form was the most insoluble in 2-propanol at 35 degrees C, and was thus concluded to be the most stable form. The epsilon-form was the most soluble, and a polymorphic transition from the epsilon- to the alpha-form was observed during solubility testing. PMID- 24211360 TI - A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study. AB - BACKGROUND: The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. METHODS: The NU-AGE study is a parallel randomized one-year trial in 1250 apparently healthy, independently living European participants aged 65-80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. DISCUSSION: The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline. PMID- 24211361 TI - Neoplastic masquerade syndromes in patients with uveitis. AB - PURPOSE: To identify the demographic and clinical characteristics, along with the frequency, of neoplastic masquerade syndromes in a tertiary uveitis clinic. DESIGN: A retrospective observational cohort. METHODS: Demographic and clinical data on all patients presenting to the National Eye Institute (NEI) with uveitis between 2004 and 2012 were used to compare neoplastic masquerade syndromes and uveitis. RESULTS: A total of 853 patients presenting with uveitis were identified. Of these, 21 (2.5%) were diagnosed with neoplastic masquerade syndromes. The average age at presentation of masquerade syndrome patients was 57 years (median, 55; range, 38-78); for uveitis, 42 years (median, 43; range, 3-98) (P = 0.0003). There were 48% females in the masquerade syndromes group, compared with 59% females in the uveitis group. African American patients represented 9% of the masquerade syndrome patients and 36% of uveitis patients (P = 0.01). Mean worse eye visual acuity was 0.89 (20/160) in neoplastic masquerade syndromes, and 0.66 (20/100) in the uveitis group (P = 0.21). Of masquerade syndrome patients, 90% had posterior inflammation, compared with 63% of uveitis patients (P = 0.006). Of those with masquerade syndromes, 48% of patients had unilateral disease, compared with 27% of the uveitis patients (P = 0.04). CONCLUSIONS: Patients with neoplastic masquerade syndromes were more likely to be older, male, or non-African American and to have posterior segment inflammation and unilateral disease. Patients with masquerade syndromes also had worse visual acuity than did uveitis patients. These differences in clinical characteristics may help to raise the suspicion for neoplastic masquerade syndromes. PMID- 24211362 TI - Optic disc planimetry, corneal hysteresis, central corneal thickness, and intraocular pressure as risk factors for glaucoma. AB - PURPOSE: To determine whether corneal hysteresis and central corneal thickness are independent risk factors for glaucoma. DESIGN: A cross-sectional population based cohort study. METHODS: Associations were tested between corneal hysteresis, measured in 1754 population-based subjects from the TwinsUK cohort, and glaucoma related endophenotypes, including intraocular pressure (IOP), vertical cup-to disc ratio, optic disc area, and optic disc cup area. Corneal hysteresis, IOP, and central corneal thickness (CCT) were measured; optic disc photographs were analyzed; and multivariable linear regression analysis was performed. RESULTS: Data were available on 1645 individuals. Multiple regression analysis showed corneal hysteresis to be significantly negatively associated with age (beta coefficient = -0.03, P < .00005) and IOP (beta coefficient = -0.06, P < .00005). Corneal hysteresis was also found to be associated with CCT (beta coefficient = 0.02, P < .0005). There was no significant association between corneal hysteresis and optic disc area (P = .6), cup area (P = .77), vertical cup-to-disc ratio (P = .51), or spherical equivalent (P = .08). CCT was also found to be significantly associated with IOP (beta coefficient = 3.3, P < .0005) and corneal hysteresis (beta coefficient = 9.4, P < .0005), but not with age (P = .59) or spherical equivalent (P = .16). CONCLUSION: In this large cohort of healthy British twins, we found no relationship between corneal hysteresis or CCT and quantitative measures of optic disc cupping, suggesting that corneal hysteresis and CCT are not independent risk factors for glaucoma. PMID- 24211363 TI - Efficient identification of miRNAs for classification of tumor origin. AB - Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acid-enhanced microarray platform, which allows for highly sensitive and specific detection of miRNA. On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%-89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%-94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy. PMID- 24211364 TI - Performance of common analysis methods for detecting low-frequency single nucleotide variants in targeted next-generation sequence data. AB - Next-generation sequencing (NGS) is becoming a common approach for clinical testing of oncology specimens for mutations in cancer genes. Unlike inherited variants, cancer mutations may occur at low frequencies because of contamination from normal cells or tumor heterogeneity and can therefore be challenging to detect using common NGS analysis tools, which are often designed for constitutional genomic studies. We generated high-coverage (>1000*) NGS data from synthetic DNA mixtures with variant allele fractions (VAFs) of 25% to 2.5% to assess the performance of four variant callers, SAMtools, Genome Analysis Toolkit, VarScan2, and SPLINTER, in detecting low-frequency variants. SAMtools had the lowest sensitivity and detected only 49% of variants with VAFs of approximately 25%; whereas the Genome Analysis Toolkit, VarScan2, and SPLINTER detected at least 94% of variants with VAFs of approximately 10%. VarScan2 and SPLINTER achieved sensitivities of 97% and 89%, respectively, for variants with observed VAFs of 1% to 8%, with >98% sensitivity and >99% positive predictive value in coding regions. Coverage analysis demonstrated that >500* coverage was required for optimal performance. The specificity of SPLINTER improved with higher coverage, whereas VarScan2 yielded more false positive results at high coverage levels, although this effect was abrogated by removing low-quality reads before variant identification. Finally, we demonstrate the utility of high sensitivity variant callers with data from 15 clinical lung cancers. PMID- 24211366 TI - Response of a three-stage process for PHA production by mixed microbial cultures to feedstock shift: impact on polymer composition. AB - Polyhydroxyalkanoates (PHA) can be produced by mixed microbial cultures (MMC) using a three-stage process. An attractive feature of MMC for PHA production is the ability to use waste/surplus feedstocks. In this study, the effect of a feedstock shift, mimicking a seasonal feedstock scenario and/or as a strategy for controlling polymer composition, on a MMC PHA production process was assessed using cheese whey (CW) and sugar cane molasses (SCM) as model feedstocks. The acidogenic stage responded immediately to the feedstock shift by changing the fermented products profile, with acetate and butyrate being the main acids produced from CW, while for SCM propionate and valerate were the dominant products. The fermentation process was then quite stable during long term operation. The PHA culture selection stage also responded quickly to the fermented feestocks shift, generating a polymer whose composition was linearly dependent on the concentration of HV and HB precursors produced in the acidogenic stage. The selected culture reached a maximum PHA content of 56% and 65% with fermented SCM and CW, respectively. Mixing fermented CW and SCM, in equal volume proportions, demonstrated the possibility of using different fermented feedstocks for tailoring polymer composition. PMID- 24211365 TI - Validation of a next-generation sequencing assay for clinical molecular oncology. AB - Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (>= 1000* average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of >= 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. PMID- 24211367 TI - Synthesis and biological evaluation of 2,6-dichloropurine bicyclonucleosides containing a triazolyl-carbohydrate moiety. AB - A series of bicyclic nucleosides containing a triazolyl-carbohydrate moiety were synthesized and their antitumor activity in vitro for human cancer cell lines was also tested. Compound 11 was synthesized efficiently with 3,6-anhydro sugar 7 as raw material, while compound 7 was prepared from 1,2;5,6-di-O-isopropylidene alpha-d-glucose. Compounds 12a-e were synthesized by treating compound 11 with alkynes, catalyzed by copper(I). After removal of the acetyl protecting groups, the target compounds 5a-e showed significant inhibitory activity against EC109, PC-3, MGC-803, and HGC-7 cell lines. PMID- 24211368 TI - N-glycosylation patterns in two alpha-l-arabinofuranosidases from Penicillium canescens belonging to the glycoside hydrolase families 51 and 54. AB - Using MALDI-TOF mass spectrometry (MS) peptide fingerprinting procedure followed by the analysis of MS data with the GlycoMod tool from the ExPASy proteomic site, N-glycosylation of two GH51 and GH54 family alpha-l-arabinofuranosidases (Abf51A and Abf54A) from Penicillium canescens was studied. Variable N-linked glycans were identified at five out of eight potential N-glycosylation sites in the Abf51A and one out of three potential N-glycosylation sites in the Abf54A. The discriminated glycans represented high-mannose oligosaccharides (Man)x(GlcNAc)2 with a number of Man residues up to 7 or the products of sequential enzymatic trimming of a high-mannose glycan with alpha-mannosidases and beta-N acetylhexosaminidases. The Abf54A peptide, containing the Asn254 glycosylation site, and one peptide from the Abf51A, containing the Asn163 glycosylation site, were found to exist not only in glycosylated, but also in a native non-modified form. PMID- 24211369 TI - Immobilized glycosylated Fmoc-amino acid for SPR: comparative studies of lectin binding to linear or biantennary diLacNAc structures. AB - A method to immobilize glycan-linked amino acids with protected alpha-amino groups, which are key intermediates to produce the desired neoglycoprotein, to a Biacore sensor chip was developed and its utility for interaction analyses was demonstrated. Two types of diN-acetyllactosamine (diLacNAc)-containing glycans, a core 2 hexasaccharide involving linear diLacNAc that is O-linked to N-(9 fluorenyl)methoxycarbonyl (Fmoc)-Thr and a biantennary diLacNAc that is N-linked to Fmoc-Asn, were used as ligands. For immobilization, the free carboxyl groups of the amino acid residues were activated with EDC/NHS, then reacted with the ethylenediamine-derivatized carboxymethyldextran sensor chip to obtain the desired ligand concentrations. Interactions of the ligands with five plant lectins were analyzed by surface plasmon resonance, and the bindings were compared. The resonance unit of each lectin was corrected by subtracting that of the reference cell on which the Fmoc-Thr-core 1 or Fmoc-Asn was immobilized as a ligand. The carbohydrate specificities of interactions were verified by preincubating lectins with their respective inhibitory sugar before injection. By steady state analysis, the Lycopersicon esculentum lectin showed a 27-fold higher affinity to linear diLacNAc than to biantennary diLacNAc, while Datura stramonium and Solanum tuberosum lectins both showed low Ka,apps of 10(6)M(-1) for these two ligands. In contrast, Ricinus communis agglutinin-120 showed a 3.2-fold higher Ka,app to biantennary LacNAc than to linear diLacNAc. A lectin purified from Pleurocybella porrigens mushroom interacted at the high affinity of 10(8)M(-1) with both linear and biantennary diLacNAcs, which identified it as a unique probe. This method provides a useful and sensitive system to analyze interactions by simulating the glycans on the cell surface. PMID- 24211370 TI - Azido derivatives of cellobiose: oxidation at C1 with cellobiose dehydrogenase from Sclerotium rolfsii. AB - We report the chemo-enzymatic synthesis of three cellobiono-1,5-lactone azido derivatives, designed as building blocks for biomedical polymer scaffolds. The synthesis is based on regioselective protection of cellobiose or 1,6-O-anhydro beta-d-cellobiose before azidation and subsequent deprotection. The oxidation to the corresponding cellobiono-1,5-lactones was investigated with 6'-azido-6' deoxycellobiose (6'N3Clb, 5), 6-azido-6-deoxycellobiose (6N3Clb, 11) and 2-azido 2-deoxycellobiose (2N3Clb, 15) under the catalysis of cellobiose dehydrogenase (CDH) from the plant-pathogenic fungus Sclerotium rolfsii. Substrate binding characteristics and kinetics of CDH for the three cellobiose azido derivatives were studied employing computational docking, steady-state and presteady-state techniques. The process of enzymatic oxidation of the cellobiose azido intermediates was optimized by using the available kinetic information. Whereas the conversion of 15 by CDH is very slow, the conversion of 5 and 11 by a regenerated, bi-enzymatic process (CDH/redox mediator/laccase/O2) is fast, quantitative and produces azido derivatives of cellobiono-1,5-lactone in an environmentally friendly, oxygen-driven process. PMID- 24211372 TI - The role of conditioning, learning and dopamine in sexual behavior: a narrative review of animal and human studies. AB - Many theories of human sexual behavior assume that sexual stimuli obtain arousing properties through associative learning processes. It is widely accepted that classical conditioning contributes to the etiology of both normal and maladaptive human behaviors. Despite the hypothesized importance of basic learning processes in sexual behavior, research on classical conditioning of the sexual response in humans is scarce. In the present paper, animal studies and studies in humans on the role of pavlovian conditioning on sexual responses are reviewed. Animal research shows robust, direct effects of conditioning processes on partner- and place preference. On the contrast, the empirical research with humans in this area is limited and earlier studies within this field are plagued by methodological confounds. Although recent experimental demonstrations of human sexual conditioning are neither numerous nor robust, sexual arousal showed to be conditionable in both men and women. The present paper serves to highlight the major empirical findings and to renew the insight in how stimuli can acquire sexually arousing value. Hereby also related neurobiological processes in reward learning are discussed. Finally, the connections between animal and human research on the conditionability of sexual responses are discussed, and suggestions for future directions in human research are given. PMID- 24211371 TI - Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism. AB - Restricted repetitive behaviors are core symptoms of autism spectrum disorders (ASDs). The range of symptoms encompassed by the repetitive behavior domain includes lower-order stereotypy and self-injury, and higher-order indices of circumscribed interests and cognitive rigidity. Heterogeneity in clinical ASD profiles suggests that specific manifestations of repetitive behavior reflect differential neuropathology. The present studies utilized a set of phenotyping tasks to determine a repetitive behavior profile for the C58/J mouse strain, a model of ASD core symptoms. In an observational screen, C58/J demonstrated overt motor stereotypy, but not over-grooming, a commonly-used measure for mouse repetitive behavior. Amphetamine did not exacerbate motor stereotypy, but had enhanced stimulant effects on locomotion and rearing in C58/J, compared to C57BL/6J. Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, had marked deficits in marble-burying. In a nose poke task for higher order repetitive behavior, C58/J had reduced holeboard exploration and preference for non-social, versus social, olfactory stimuli, but did not demonstrate cognitive rigidity following familiarization to an appetitive stimulus. Analysis of available high-density genotype data indicated specific regions of divergence between C58/J and two highly-sociable strains with common genetic lineage. Strain genome comparisons identified autism candidate genes, including Cntnap2 and Slc6a4, located within regions divergent in C58/J. However, Grin1, Nlgn1, Sapap3, and Slitrk5, genes linked to repetitive over-grooming, were not in regions of divergence. These studies suggest that specific repetitive phenotypes can be used to distinguish ASD mouse models, with implications for divergent underlying mechanisms for different repetitive behavior profiles. PMID- 24211374 TI - Developmental psychoneuroimmunology: from bench to bedside. PMID- 24211375 TI - Neurocognitive disturbances associated with acute infectious mononucleosis, Ross River fever and Q fever: a preliminary investigation of inflammatory and genetic correlates. AB - Disturbances in neurocognitive performance are a core feature of the acute sickness response to infection; however the underlying mechanisms remain unclear. The current study used a computerised battery to assess neurocognitive functioning in subjects enrolled in the Dubbo Infection Outcomes Study (n=107) - a prospective cohort of subjects followed from documented acute infection with Epstein Barr virus, Ross River virus, or Coxiella burnetii until recovery. Subjects were assessed when ill, and a subset again after complete recovery. Associations between sickness-related cognitive disturbances and single nucleotide polymorphisms (SNPs) in cytokine (interleukin [IL]-6, IL-10, tumor necrosis factor-alpha and interferon-gamma) and neurobehavioral genes (serotonin transporter and catechol-O-methyltransferase) were explored. During acute infection, subjects exhibited slower matching-to-sample responses (p=0.03), poorer working memory capacity (p=0.014), mental planning (p=0.045), and dual attention task performance (p=0.02), and required longer to complete discordant Stroop trials (p=0.01) compared to recovery. Objective impairments correlated significantly with self-reported symptoms (p<0.05) as well as levels of the inflammation marker, C-reactive protein (p=0.001). Linear regression analysis identified an association between neurocognitive disturbance during acute illness and functional polymorphisms in inflammatory cytokine genes. Specifically, the high cytokine producing G allele of the IL-6-174G/C SNP was associated with poorer neurocognitive performance when subjects were ill (p=0.027). These findings confirm that acute infection impacts on neurocognitive performance, manifesting as slowed responses and impaired performance on complex tasks requiring higher-order functioning which has important real-world implications. The data provide the first preliminary evidence for a role of a genetic predisposition to more intense inflammatory responses in objective neurocognitive disturbances during acute infections. These associations require replication in a larger sample size. PMID- 24211376 TI - Demonstration of laparoscopic resection of uterine sacculation (niche) with uterine reconstruction. AB - STUDY OBJECTIVE: To demonstrate a technique of laparoscopic excision of uterine sacculation (niche) with uterine reconstruction. DESIGN: Narrated video presenting a step-by-step explanation of a laparoscopic technique for excision of uterine sacculation (niche) with uterine reconstruction using a narrated video (Canadian Task Force classification III). SETTING: Laparoscopic excision of uterine sacculation (niche) is a fertility-sparing technique for use in a selected group of patients who do not respond to medical treatment and in whom definitive treatment via hysterectomy is not an option. INTERVENTIONS: Laparoscopic excision of uterine sacculation (niche) is performed by excising the uterine defect after initial reflection of the uterovesical fold. The area of uterine defect is identified preoperatively using flexible hysteroscopy. Once the margins of the defect are identified laparoscopically, it is circumferentially excised. The uterine manipulator helps to identify the cervical canal. Reconstruction is performed using interrupted 1 Vicryl sutures using an extracorporeal technique for secure tissue apposition. An adhesion barrier is then applied around the reconstructed area. CONCLUSION: Excision of uterine sacculation (niche) with uterine reconstruction is a conservative surgical laparoscopic technique that should be considered in a selected group of patients in whom fertility sparing is desired and after medical therapy including progestogens, combined contraceptive pills, or the Mirena coil has failed to resolve symptoms. PMID- 24211377 TI - Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. AB - OBJECTIVES: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We evaluated 141 patients who were planned to receive acyclovir at 200mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. RESULTS: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. CONCLUSIONS: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease. PMID- 24211373 TI - Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies. AB - Human neuroimaging studies suggest that neural cue reactivity is strongly associated with indices of drug use, including addiction severity and treatment success. However, little is known about factors that modulate cue reactivity. The goal of this review, in which we survey published fMRI and PET studies on drug cue reactivity in cocaine, alcohol, and tobacco cigarette users, is to highlight major factors that modulate brain reactivity to drug cues. First, we describe cue reactivity paradigms used in neuroimaging research and outline the brain circuits that underlie cue reactivity. We then discuss major factors that have been shown to modulate cue reactivity and review specific evidence as well as outstanding questions related to each factor. Building on previous model-building reviews on the topic, we then outline a simplified model that includes the key modulatory factors and a tentative ranking of their relative impact. We conclude with a discussion of outstanding challenges and future research directions, which can inform future neuroimaging studies as well as the design of treatment and prevention programs. PMID- 24211378 TI - Pandemic influenza A/H1N1 2009 antibodies in the metropolitan area of Buenos Aires in Argentina. AB - OBJECTIVE: To estimate the infection prevalence in Buenos Aires during the outbreak of pandemic influenza A/H1N1 2009 virus (A(H1N1)pdm09). METHODS: A(H1N1)pdm09-specific antibodies were measured by hemagglutination inhibition assay in human serum samples collected 6 months after the outbreak and before the introduction of the A(H1N1)pdm09 vaccine in Argentina. Baseline levels of cross reactive antibodies to A(H1N1)pdm09 were determined by testing 162 serum samples collected before 2009. RESULTS: The overall seroprevalence of A(H1N1)pdm09 in 150 children and 427 adults was 28.9% (95% confidence interval (CI) 25-33%), with a 58.0% prevalence in children <19 years of age and an 18.7% prevalence in adults >=19 years of age (p<0.001). The prevalence was 43.5% in children <5 years old and 60.6% among children aged 5-18 years. The prevalence in adults declined with increasing age: 24.9% in 19-39-year-olds, 9.7% in 40-59-year-olds, and 8.1% in those >=60 years old. The prevalence of specific A(H1N1)pdm09 antibodies was higher compared with the baseline in children (p=0.014), adolescents (p<0.001), and adults <40 years old (p=0.017). Seroprevalence in health care workers was not different from the rest of the population (13.6% vs. 19.3%, respectively; p=0.421). CONCLUSIONS: The prevalence of specific A(H1N1)pdm09 antibodies was high at 28.9%. The highest prevalence was observed in children, adolescents, and young adults. PMID- 24211379 TI - Passive remediation of coalbed natural gas co-produced water using zeolite. AB - Coalbed natural gas (CBNG) co-produced waters can contain sodium (Na(+)) concentrations that may be environmentally detrimental if discharged to receiving bodies of water or applied to land surfaces. A field demonstration and companion laboratory studies were conducted to evaluate the use of a Bear River zeolite (BR zeolite) for mitigating impacts associated with Na(+) in CBNG waters. Bench-scale kinetic and adsorption isotherm studies were performed to determine both the rate and extent of sodium Na(+) adsorption and assess the effects of bicarbonate (HCO3(-)) and chloride (Cl(-)) anions. Results of these studies showed that the adsorption of Na(+) on BR-zeolite followed the Langmuir adsorption model with maximum adsorption equal to 21 and 18 g Na(+)/kg zeolite with 0.0012 and 0.0006 L/mg Langmuir coefficients (KL) for sodium bicarbonate and sodium chloride, respectively. The kinetics study indicated that the sorption of Na(+) was inversely related to the size of the zeolite particles with significantly greater adsorption for smaller particles. The field demonstration evaluated the effectiveness of BR-zeolite for mitigating infiltration losses from Na(+) in CBNG waters. The field site utilized 12 open boreholes, each installed to a depth of approximately 1.8 m. Each borehole was lined with a 3.0 m long, 15 cm diameter schedule 40 PVC pipe and fitted with an automatic data logging pressure transducer for measuring water levels over time. The BR-zeolite was found to mitigate much of the deleterious effect that high sodium adsorption ratio (SAR = 27 (mol/m(3))(1/2)) CBNG co-produced water had on soil permeabilities. PMID- 24211380 TI - Examining the relative effects of fire weather, suppression and fuel treatment on fire behaviour--a simulation study. AB - Large budgets are spent on both suppression and fuel treatments in order to reduce the risk of wildfires. There is little evidence regarding the relative contribution of fire weather, suppression and fuel treatments in determining the risk posed from wildfires. Here we undertake a simulation study in the Sydney Basin, Australia, to examine this question using a fire behaviour model (Phoenix Rapidfire). Results of the study indicate that fire behaviour is most strongly influenced by fire weather. Suppression has a greater influence on whether a fire reaches 5 ha in size compared to fuel treatments. In contrast, fuel treatments have a stronger effect on the fire size and maximum distance the fire travels. The study suggests that fire management agencies will receive additional benefits from fuel treatment if they are located in areas which suppression resources can respond rapidly and attempt to contain the fires. No combination of treatments contained all fires, and the proportion of uncontained fires increased under more severe fire weather when the greatest number of properties are lost. Our study highlights the importance of alternative management strategies to reduce the risk of property loss. PMID- 24211381 TI - While waiting for the answer: a critical review of meta-studies of tropical forest management. AB - This paper assesses the existing meta-studies of forestry conservation. Most of meta-studies have focused on either the performance of protected areas or the community managed forests. Only one article has directly compared the performance of the two management forms. Porter-Bolland et al. (2012) claim that community managed forests presented a lower mean deforestation rate than protected areas. We found several statistical problems and problems with definitions in all meta studies, and we argue that the data available, not the least for community managed forest, does not allow for genuine global comparison. Using similar measuring techniques and same definitions when comparing the two management forms are necessities when trying to reach a general conclusion about which management form is best. PMID- 24211382 TI - Effect of human disturbance on the prey of tiger in the Chitwan National Park- implications for park management. AB - Chitwan National Park is surrounded by large settlements of people who exploit the areas where tigers and their prey occur. In this study, we measured the associations between the abundance of the prey of tiger with habitat, topographic, predator and human disturbance variables, using canonical correspondence analysis. We show that the abundance of hog deer is closely associated with areas of tall grassland and floodplains, while that of other ungulate species is associated with that of forests and short grasslands. Primates were mainly abundant in riverine and mixed forests. Abundances of most species, except hog deer and wild pig, were more closely associated with areas of forests than with open areas, because the latter were mainly occupied by humans and livestock. The presence of the species studied was closely associated with habitat and disturbance variables. Proximity of water holes was more closely associated with the presence of ungulates than primates. There were close associations between human disturbance and abundances of primates and muntjac, possibly because these species are more tolerant and adapted to human disturbance. However, the major prey species of tiger were negatively associated with human disturbance. As a consequence, human disturbance has resulted in a decline in the abundance of tigers and the lack of prey could result in their extinction in the Chitwan NP. Therefore, in terms of the conservation and management of the park, minimizing human disturbance of wildlife habitats and restoration of a buffer zone forest should be the prime objectives. PMID- 24211383 TI - Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions. AB - In addition to detrimental inflammation, widespread axon degeneration is an important feature of multiple sclerosis (MS) pathology and a major correlate for permanent clinical deficits. Thus, treatments that combine immunomodulatory and neuroprotective effects are beneficial for MS. Using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of MS, we recently showed that daily treatment with the phosphodiesterase 5 (PDE5) inhibitor sildenafil at peak disease rapidly ameliorates clinical symptoms and neuropathology (Pifarre et al., 2011). We have now investigated the immunomodulatory and neuroprotective actions of sildenafil treatment from the onset of EAE when the immune response prevails and show that early administration of the drug prevents disease progression. Ultrastructural analysis of spinal cord evidenced that sildenafil treatment preserves axons and myelin and increases the number of remyelinating axons. Immunostaining of oligodendrocytes at different stages of differentiation showed that sildenafil protects immature and mature myelinating oligodendrocytes. Brain-derived neurotrophic factor (BDNF), a recognized neuroprotectant in EAE, was up-regulated by sildenafil in immune and neural cells suggesting its implication in the beneficial effects of the drug. RNA microarray analysis of spinal cord revealed that sildenafil up-regulates YM-1, a marker of the alternative macrophage/microglial M2 phenotype that has neuroprotective and regenerative properties. Immunostaining confirmed up-regulation of YM-1 while the classical macrophage/microglial activation marker Iba-1 was down-regulated. Microarray analysis also showed a notable up-regulation of several members of the granzyme B cluster (GrBs). Immunostaining revealed expression of GrBs in Foxp3+-T regulatory cells (Tregs) suggesting a role for these proteases in sildenafil-induced suppression of T effector cells (Teffs). In vitro analysis of splenocytes from sildenafil-treated animals showed down-regulation of Th1/Th2/Th17 responses while Tregs were up-regulated. Additionally, sildenafil treatment prevented MOG specific IgG2b accumulation in serum. Taken together these data demonstrates that daily sildenafil treatment from the initiation of EAE symptoms prevents further clinical deterioration by stimulating immunomodulatory and neuroprotective mechanisms. Importantly, we also show here that sildenafil enhances the ability of human Tregs from healthy donors to down-regulate the proliferation of Teffs in vitro, strongly supporting the potential of sildenafil for therapeutic intervention in MS. PMID- 24211384 TI - Identification and expression pattern analysis of Piwi genes during the spermiogenesis of Portunus trituberculatus. AB - The Piwi genes have an important role in stem cell development, gametogenesis and RNA interference in diverse organisms. So far, most of the studies have focused on the function of Piwis in vertebrates, but their function during spermiogenesis in invertebrates still remains largely unclear. In order to investigate the function of Piwis during spermiogenesis in the crab Portunus trituberculatus, we use RT-PCR and RACE to identify three Piwi complete cDNA sequences from the total RNA of the testis in P. trituberculatus. The deduced amino acid sequences of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 showed that each contains a well conserved PAZ domain and PIWI domain. RT-PCR analyzed the tissue expression pattern of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 in the testis, heart, muscle, hepatopancreas and gill. All of the Piwis are found in germ cells of adult testis in P. trituberculatus by in situ hybridization, suggesting that these genes may play function during spermiogenesis in this species. PMID- 24211385 TI - A novel P2RX2 mutation in an Italian family affected by autosomal dominant nonsyndromic hearing loss. AB - Hereditary hearing loss (HHL) is a common disorder accounting for at least 60% of prelingual deafness. It is characterized by a large genetic heterogeneity, and despite the presence of a major gene, still there is a need to search for new causative mutations/genes. Very recently, a mutation within ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) gene (P2RX2) at DNFA41 locus has been reported leading to a bilateral and symmetrical sensorineural non syndromic autosomal dominant HHL in two Chinese families. We performed a linkage analysis in a large Italian family with a dominant pattern of inheritance showing a significant 3.31 LOD score in a 2Mb region overlapping with the DNFA41 locus. Molecular analyses of P2RX2 identified a novel missense mutation (p.Gly353Arg) affecting a residue highly conserved across species. Visual inspection of the protein structure as obtained from comparative modeling suggests that substitution of the small glycine residue with a charged bulky residue such as an arginine that is close to the 'neck' of the region responsible for ion channel gating should have a high energetic cost and should lead to a severely destabilization of the fold. The identification of a second most likely causative mutation in P2RX2 gene further supports the possible role of this gene in causing autosomal dominant HHL. PMID- 24211386 TI - Identification and characterization of granule bound starch synthase I (GBSSI) gene of tartary buckwheat (Fagopyrum tataricum Gaertn.). AB - Tartary buckwheat (Fagopyrum tataricum Gaertn.) is increasingly considered as an important functional food material because of its rich nutraceutical compounds. Reserve starch is the major component of tartary buckwheat seed. However, the gene sequences and the molecular mechanism of tartary buckwheat starch synthesis are unknown so far. In this study, the complete genomic sequence and full-size cDNA coding tartary buckwheat granule-bound starch synthase I (FtGBSSI), which is responsible for amylose synthesis, were isolated and analyzed. The genomic sequence of the FtGBSSI contained 3947 nucleotides and was composed of 14 exons and 13 introns. The cDNA coding sequence of FtGBSSI shared 63.3%-75.1% identities with those of dicots and 56.6%-57.5% identities with monocots (Poaceae). In deduced amino acid sequence of FtGBSSI, eight motifs conserved among plant starch synthases were identified. A cleavage at the site IVC?G of FtGBSSI protein produces the chloroplast transit sequence of 78 amino acids and the mature protein of 527 amino acids. The FtGBSSI mature protein showed an identity of 73.4%-77.8% with dicot plants, and 67.6%-70.4% with monocot plants (Poaceae). The mature protein was composed of 20 alpha-helixes and 16 beta-strands, and folds into two main domains, N- and C-terminal domains. The critical residues which are involved in ADP and sugar binding were predicted. These results will be useful to modulate starch composition of buckwheat kernels with the aim to produce novel improved varieties in future breeding programs. PMID- 24211387 TI - Restriction enzyme cutting site distribution regularity for DNA looping technology. AB - The restriction enzyme cutting site distribution regularity and looping conditions were studied systematically. We obtained the restriction enzyme cutting site distributions of 13 commonly used restriction enzymes in 5 model organism genomes through two novel self-compiled software programs. All of the average distances between two adjacent restriction sites fell sharply with increasing statistic intervals, and most fragments were 0-499 bp. A shorter DNA fragment resulted in a lower looping rate, which was also directly proportional to the DNA concentration. When the length was more than 500 bp, the concentration did not affect the looping rate. Therefore, the best known fragment length was longer than 500 bp, and did not contain the restriction enzyme cutting sites which would be used for digestion. In order to make the looping efficiencies reach nearly 100%, 4-5 single cohesive end systems were recommended to digest the genome separately. PMID- 24211388 TI - Transcription of the rpsO-pnp operon of Streptomyces coelicolor involves four temporally regulated, stress responsive promoters. AB - Primer extension with RNA from an RNase III null mutant of Streptomyces coelicolor M145 and a primer complementary to the polynucleotide phosphorylase gene revealed two major extension products. Two different extension products were observed using RNA from either wild type M145 or the null mutant with a primer complementary to rpsO. Mapping of the 5'-ends of these extension products to the rpsO-pnp intergenic region indicated that all four putative transcription start sites were preceded by possible promoter sequences. These putative promoters were synthesized by the PCR and cloned into pIPP2, a xylE-based streptomycete promoter probe vector. Transfer of the pIPP2 derivatives to S. coelicolor and catechol dioxygenase assays demonstrated that all four cloned fragments had promoter activity in vivo. The activities of the four promoters changed over the course of growth of S. coelicolor and studies in three sigma factor mutant strains demonstrated that three of the promoters were sigma(B) dependent. Northern blotting studies showed that the levels of the rpsO-pnp transcripts remained relatively constant over the course of growth of S. coelicolor M145, but that on a molar basis, the levels of the readthrough and pnp transcripts were considerably lower than those of rpsO. PNPase is a cold shock protein in S. coelicolor and the activity of the rpsO-pnp promoters increased during cold shock at 10 degrees , resulting in a two-fold increase in PNPase activity, compared with the activity at 30 degrees . PMID- 24211389 TI - Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families. AB - Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM. PMID- 24211390 TI - Effects of Phaseolus vulgaris (Fabaceae) seed coat on the embryonic and larval development of the cowpea weevil Callosobruchus maculatus (Coleoptera: Bruchidae). AB - Bruchid beetles infest various seeds. The seed coat is the first protective barrier against bruchid infestation. Although non-host seed coats often impair the oviposition, eclosion and survival of the bruchid Callosobruchus maculatus larvae, morphological and biochemical aspects of this phenomenon remain unclear. Here we show that Phaseolus vulgaris (non-host) seed coat reduced C. maculatus female oviposition about 48%, increased 83% the seed penetration time, reduced larval mass and survival about 62 % and 40 % respectively. Interestingly, we found no visible effect on the major events of insect embryogenesis, namely the formation of the cellular blastoderm, germ band extension/retraction, embryo segmentation, appendage formation and dorsal closure. Larvae fed on P. vulgaris seed coat have greater FITC fluorescence signal in the midgut than in the feces, as opposed to what is observed in control larvae fed on Vigna unguiculata. Cysteine protease, alpha-amylase and alpha-glucosidase activities were reduced in larvae fed on P. vulgaris natural seed coat. Taken together, our results suggest that although P. vulgaris seed coat does not interfere with C. maculatus embryonic development, food digestion was clearly compromised, impacting larval fitness (e.g. body mass and survivability). PMID- 24211391 TI - JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity. AB - Embryonic stem (ES) cells are pluripotent cells with the capacity for unlimited self-renewal or differentiation. Inhibition of MAPK pathways enhances mouse ES cell pluripotency characteristics. Compared to wildtype ES cells, jnk2(-/-) ES cells displayed a much higher growth rate. To determine whether JNKs are required for stem cell self-renewal or differentiation, we performed a phosphorylation kinase array assay to compare mouse ES cells under LIF+ or LIF- culture conditions. The data showed that activation of JNKs was induced by LIF withdrawal. We also found that JNK1 or 2 phosphorylated Klf4 at threonines 224 and 225. Activation of JNK signaling and phosphorylation of Klf4 inhibited Klf4 transcription and transactivation activity. Importantly, jnk1(-/-) and jnk2(-/-) murine embryonic fibroblasts (MEFs) exhibited a significantly greater potency in the ability to increase the number of iPS colonies compared with jnk wildtype MEFs. Overall, our results demonstrated that JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity. PMID- 24211392 TI - Hymenaea stigonocarpa Mart. ex Hayne: A tropical medicinal plant with intestinal anti-inflammatory activity in TNBS model of intestinal inflammation in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark and fruit pulp of Hymenaea stigonocarpa Mart ex. Hayne (Fabaceae) has been popularly used to treat inflammation and gastrointestinal diseases including ulcers, diarrhea and gastric pain. The aim of this study was to investigate the intestinal anti-inflammatory activity of a methanol extract derived from the stem bark and diet with fruit pulp of Hymenaea stigonocarpa in the TNBS model of intestinal inflammation in rats. MATERIAL AND METHODS: The intestinal anti-inflammatory activity of stem bark extract (100, 200 and 400mg/kg) and fruit pulp (10% and 5% in diet) was measured against the intestinal inflammatory process induced by TNBS (trinitrobenzesulphonic acid) in rats. The protective effects were evaluated as follows: evaluation of intestinal damage (damage score, extension of lesion, colon weight/length ratio), incidence of diarrhea and adherence to adjacent organs, colon glutathione (GSH) and malondialdehyde (MDA) contents, myeloperoxidase (MPO) and alkaline phosphatase (AP) activities. In addition, in vitro studies on lipid peroxidation in rat brain membranes and phytochemical profile were performed with both stem bark and fruit pulp. RESULTS: Treatment with 100, 200 and 400mg/kg of stem bark extract and 10% fruit pulp flour showed protective effects in the TNBS-induced colon damage, which was related to inhibition of MPO and AP activities, reduction in colon MDA content, and counteraction of GSH depletion induced by inflammatory process. A concentration-dependent inhibitory effect on the lipid peroxidation in rat brain membranes for stem bark and fruit pulp was determined, with an IC50 value of 5.25 +/- 0.23 MUg/mL and 27.33 +/- 0.09 MUg/mL, respectively. Similar phytochemical composition was observed in fruit and stem bark, including mainly flavonoids, condensed tannins and terpenes. CONCLUSIONS: Stem bark extract and fruit pulp flour of Hymenaea stigonocarpa prevented TNBS-induced colonic damage in rats and this protective effect were associated to an improvement of intestinal oxidative stress. The observed anti-inflammatory and antioxidant effects may be associated to the presence of flavonoids and tannins in the stem bark and fruit pulp of Hymenaea stigonocarpa. PMID- 24211393 TI - The use of the local flora in Switzerland: a comparison of past and recent medicinal plant knowledge. AB - ETHNOPHARMACOLOGICAL RELEVANCE: This analysis of documented medicinal plants of the Swiss Flora over the last two millennia provides a rich source of knowledge on earlier uses of plants and use patterns of the local flora. We ask which local plant species were used during different time periods of the last 2000 years and how the numbers of species and the use intensity of specific plant families, growth forms and habitats changed over time. MATERIALS AND METHODS: Totally 25 herbals from the antiquity, monastic medicine, Renaissance, early modern era and the contemporary time as well as five recent ethnobotanical studies were considered. Use patterns were analysed with the Bayesian approach. RESULTS: A total of 768 species, i.e. 32% of the vascular plants of the Swiss Flora have been documented as medicinal plants. Numbers increase until the monastic period (366 spp.) and the Renaissance (476) and remain relatively stable since then (modern and contemporary era: 477). But, 465 formerly documented species do not occur in the ethnobotanical studies and thus seem not to be used any more. Overall, 104 species are documented through all time periods. Archeophytes, trees and forest plants are generally overrepresented in herbals from all time periods while plants from above the timberline are generally underrepresented. Most widely used are the Lamiaceae and Apiaceae. CONCLUSION: A constant body of medicinal plant knowledge in Switzerland exists since ancient time. This knowledge was always influenced by knowledge from neighboring countries and no "typical Swiss specialties" seem to exist. Medicinal plants are not randomly chosen from the available flora. Certain species are deliberately introduced others are neglected. This process, which is still ongoing, can be traced back with the help of herbals to the antiquity. PMID- 24211394 TI - 'Ashvagandharishta' prepared using yeast consortium from Woodfordia fruticosa flowers exhibit hepatoprotective effect on CCl4 induced liver damage in Wistar rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Consortium of yeasts sourced from traditionally used Woodfordia fruticosa flowers proved to be beneficial for fermenting Ashvagandharishta. It resulted in faster fermentation, acceptable organoleptic properties and demonstrable hepatoprotective potential in CCl4 induced hepatotoxicity. To formulate Ashvagandharishta using consortium of yeasts and to investigate its physiochemical parameters. Standardize the formulation with the help of standard withaferin-A and withanolide-A and to evaluate its hepatoprotective potential in CCl4 induced hepatotoxicity in the rat model. MATERIAL AND METHODS: Ashvagandharishta was prepared using a 5% consortium of yeasts and ascertained its quality through physiochemical and phytochemical investigation. Withaferin-A and withanolide-A was simultaneously estimated by HPLC for standardization. Hepatoprotective potential was evaluated by administering 2.31 and 1.15 ml/kg doses while considering biochemical parameters like serum AST, ALT, ALP and lipid profile. Gene expression study was carried out for the expression of antioxidant and inflammatory genes such as CAT, GPx and proinflammatory gene IL-6. Histopathology of liver was also studied with the help of H&E staining. RESULTS: Ashvagandharishta was found organolepticaly acceptable with optimized physiochemical parameters. Withaferin-A and withanolide-A in Ashvagandharishta estimated as 0.3711, 0.7426 (%w/v), respectively. In the CCl4 induced hepato-toxicity model, Ashvagandharishta-2.31ml/kg dose showed significant decrease in elevated hepatic level of AST(p<0.001), ALT(p<0.01) and ALP(p<0.001). Both doses of Ashvagandharishta showed significant reduction of TG, Cholesterol, VLDL and LDL in serum, with corresponding reduction of (p<0.001) serum-HDL. Ashvagandharishta also showed increased serum protein (p<0.05) and albumin (p<0.01) with decrease in bilirubin (p<0.01). Additionally, Ashvagandharishta administration revealed up-regulation in antioxidant genes such as CAT and GPx in liver with concomitant down-regulation in proinflammatory IL 6gene (p<0.01). Histopathological parameters revealed restoration of normal tissue architecture by both doses of Ashvagandharishta. CONCLUSIONS: Consortium of yeasts from Woodfordia fruticosa flowers showed better fermentation pattern for Ashvagandharishta produced with acceptable organoleptic properties. Hepatoprotection shown by Ashvagandharishta was mainly through prevention of oxidative damage. Up-regulation of CAT and GPx genes and corresponding down regulation of proinflammatory IL6 gene was revealed as possible mechanism of its action. PMID- 24211395 TI - Antrodia salmonea inhibits TNF-alpha-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-kappaB and up regulation of Nrf2 signaling pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia salmonea (AS) is known as a traditional Chinese medicine, but very few biological activities have been reported. MATERIALS AND METHODS: The present study was aimed to investigate the anti angiogenic and anti-atherosclerotic potential of the fermented culture broth of AS against tumor necrosis factor-alpha (TNF-alpha)-stimulated human endothelial (EA.hy 926) cells. RESULTS: The non-cytotoxic concentrations of AS significantly inhibited TNF-alpha-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-alpha-induced activity and expression of matrix metalloproteinase-9 (MMP-9), and cell-surface expression of intercellular adhesion molecule-1 (ICAM-1), which was associated with abridged adhesion of U937 leukocytes to endothelial cells. Moreover, AS significantly down regulated TNF-alpha-induced nuclear translocation and transcriptional activation of nuclear factor kappaB (NF-kappaB) followed by suppression of I-kappaB degradation and phosphorylation of I-kappaB kinase-alpha (IKKalpha). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCLC), which was reasoned by nuclear translocation and transactivation of NF-E2 related factor 2 (Nrf2)/antioxidant response element (ARE). Furthermore, HO-1 knockdown by HO-1 specific shRNA diminished the protective effects of AS on TNF-alpha-stimulated invasion, tube formation, and U937 adhesion in EA.hy 926 cells. CONCLUSIONS: Taken together, these results suggest that Antrodia salmonea may be useful for the prevention of angiogenesis and atherosclerosis. PMID- 24211396 TI - Traditional usage, phytochemistry and pharmacology of the South African medicinal plant Boophone disticha (L.f.) Herb. (Amaryllidaceae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Boophone disticha is the most common member of the South African Amaryllidaceae used extensively in traditional medicine of the various indigenous population groups, including the Sotho, Xhosa and Zulu as well as the San. This survey was carried out to identify and highlight areas relevant to the traditional usage of Boophone disticha. Pharmacological aspects were examined with the purpose of reconciling these with the traditional usage of the plant. In relation to phytochemical make-up, particular attention was paid on how its alkaloid constitution might corroborate the various biological effects manifested by the plant. MATERIALS AND METHODS: Information gathering involved the use of four different database platforms, including Google Scholar, ScienceDirect, SciFinder((r)) and Scopus. Arrangement and detailing of this information is as reflected in the various sections of the paper. RESULTS: Sixteen categories were identified under which Boophone disticha finds use in traditional medicine. These were shown to include general usage purposes, such as 'cultural and dietary', 'well-being', 'personal injury', 'divinatory purposes', 'psychoactive properties' and 'veterinary uses'. Furthermore, traditional usage was seen to involve six body systems, including functions pertaining to the circulatory, gastrointestinal, muscular, neurological, respiratory and urinary systems. The four remaining categories relate to use for inflammatory conditions, cancer, malaria and tuberculosis. Overall, three areas were discernible in which Boophone disticha finds most usage, which are (i) ailments pertaining to the CNS, (ii) wounds and infections, and (iii) inflammatory conditions. In addition, several aspects pertaining to the toxic properties of the plant are discussed, including genotoxicity, mutagenicity and neurotoxicity. CONCLUSION: The widespread ethnic usage of Boophone disticha has justified its standing as a flagship for the Amaryllidaceae and its relevance to South African traditional medicine. Furthermore, its promising pharmacological and phytochemical profiles have stimulated significant interest in the clinical realm, especially in the areas of cancer and motor neuron disease chemotherapy. These collective properties should prove useful in steering the progress of the plant towards a wider audience. PMID- 24211397 TI - Multitargeted protective effect of Abacopteris penangiana against carrageenan induced chronic prostatitis in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Abacopteris penangiana (Hook.) Ching (AP) is traditionally used in Chinese medicine to promote blood circulation, remove blood stasis and dampness and for the treatment of edema and inflammation. In order to further support and develop the traditional use of Abacopteris penangiana as Chinese folk medicine, the aim of this study is to investigate the protective effect of the total flavanol glycosides (TFA) from AP and its acid hydrolysate (AHT) on chronic non-bacterial prostatitis (CNP) by measuring the levels of oxidative stress and inflammatory responses in rats. MATERIALS AND METHODS: First, the antioxidant and anti-inflammatory activities of AHT and TFA were investigated. Then the experimental chronic non-bacterial prostatitis was induced by carrageenan. The prostate index (PI) and prostate specific antigen (PSA) were determined. The activities of AHT and TFA on inhibiting free radicals and oxidative stress were investigated. Subsequently, the degree of chronic inflammatory cell infiltrates, acinar changes and interstitial fibrosis were evaluated by histopathological examination. In addition, the relative inflammatory factors, tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), cyclooxygenase-2 (COX-2), prostaglandin E2 (PEG2), transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) were measured. Finally, the prostatic expression of nuclear transcription factor kappaB (NF-kappaB) was determined by immunohistochemistry and western blot analysis. RESULTS: The whole results showed that AHT and TFA had strong antioxidant and anti-inflammatory activities. In CNP model, AHT and TFA successfully decreased PI and PSA. The activities of antioxidant enzymes in AHT or TFA group were enhanced. Additionally, a morphometric analysis of the prostate gland of AHT or TFA treated rats demonstrated a significant reduction in chronic inflammatory cell infiltrates and interstitial fibrosis compared to model group. The reduced values of TNF-alpha, IL-1beta, COX-2, PEG2, inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were observed both in AHT and TFA treated groups. Moreover, the levels of TGF-beta1 and CTGF in AHT and TFA treated groups were significantly decreased along with the alleviation of the inflammatory state of the prostate gland. Besides, the prostatic expression of NF-kappaB was inhibited. CONCLUSIONS: These results suggest that AHT and TFA have anti prostatitis properties via inhibiting oxidative stress, NF-kappaB dependent pro inflammatory cytokines, fibrosis-related factors and antinociceptive activity. Hence, AP represents a potential herb for the treatment of prostatitis. PMID- 24211398 TI - Extension of dynamic range of sensitive nanoparticle-based immunoassays. AB - Nanoparticles have successfully been employed in immunometric assays that require high sensitivity. Certain analytes, however, require dynamic ranges (DRs) around a predetermined cut-off value. Here, we have studied the effects that antibody orientation and addition of free solid-phase and detection antibodies have on assay sensitivity and DR in traditional sandwich-type immunoassays. D-dimer and cardiac troponin I (cTnI), both routinely used in critical care testing, were applied as model analytes. The assays were performed in microtitration wells with preimmobilized solid-phase antibody. Inherently fluorescent nanoparticles coated with second antibody were used to detect the analyte. The selection of antibody orientation and addition of free solid-phase or detection antibody, with nanoparticles and calibrator, desensitized the assays and extended the DR. With D dimer the upper limit of the DR was improved from 50 to 10,000 ng/ml, and with cTnI from 25 to 1000 ng/ml. Regression analysis with the Stago STA Liatest D dimer assay yielded a slope (95% confidence interval) of 0.09 (0.07-0.11) and a y intercept of -7.79 (-17.87-2.29)ng/L (n=65, r=0.906). Thus it is concluded that Europium(III)-chelate-doped nanoparticles can also be employed in immunoassays that require wide DRs around a certain cut-off limit. PMID- 24211399 TI - Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome. AB - OBJECTIVE: The primary aim of this study was to determine the prevalence of occult gynecologic malignancy at the time of risk reducing surgery in patients with Lynch Syndrome. A secondary aim was to determine the prevalence of occult gynecologic malignancy at the time of surgery for non-prophylactic indications in patients with Lynch Syndrome. METHODS: A retrospective review of an Inherited Colorectal Cancer Registry found 76 patients with Lynch syndrome (defined by a germline mutation in a DNA mismatch repair gene) or hereditary nonpolyposis colorectal cancer (HNPCC) (defined by Amsterdam criteria) who had undergone hysterectomy and/or salpingo-oophorectomy for a prophylactic or non-prophylactic indication. Indications for surgery and the prevalence of cancer at the time of each operation were reviewed. RESULTS: 24 of 76 patients underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy for Lynch syndrome or HNPCC. In 9 of these patients, a benign indication for surgery was also noted. 4 of 24 patients (17%, 95% CI = 5-38%) were noted to have cancer on final pathology. 20 of 76 patients (26%) undergoing operative management for any indication were noted to have occult malignancy on final pathology. CONCLUSIONS: Patients should be counseled about the risks of finding gynecologic cancer at the time of prophylactic or non-prophylactic surgery for Lynch syndrome and HNPCC, and the potential need for additional surgery. PMID- 24211400 TI - Nibrin is a marker of clinical outcome in patients with advanced serous ovarian cancer treated in the phase III OVA-301 trial. AB - OBJECTIVE: This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: A statistically significant correlation between high levels of nibrin and lower ORR (P=0.03), shorter PFS (P=0.007) and shorter OS (P=0.01) was observed. After stratification, in patients with platinum-sensitive disease treated with the combination of trabectedin plus PLD, high levels of nibrin correlated with lower ORR (P=0.01) and shorter PFS (P=0.02). A better clinical outcome (ORR, PFS and OS) was also associated to low levels of CHK2 in trabectedin plus PLD treated patients. No correlations were found in PLD-treated patients. According to the results of a multivariate analysis, there was a statistically significant correlation between high nibrin (P=0.001) and low BRCA2 levels (P=0.03) and a worse PFS, and between high nibrin levels and a worse OS (P=0.006). CONCLUSION: Our results indicate that high nibrin expression seems to be associated with a worse clinical outcome in serous ROC, particularly in patients treated with the combination trabectedin plus PLD. Prospective studies to determine clinical usefulness of nibrin as a possible biomarker in other series of patients with ROC are warranted. PMID- 24211401 TI - Clinical predictors of long-term survival for stage IVB uterine papillary serous carcinoma confined to the abdomen. AB - OBJECTIVE: To identify clinical predictors of long-term survival in women with FIGO Stage IVB uterine papillary serous carcinoma (UPSC) confined to the abdomen METHODS: Records were reviewed for 48 patients with Stage IVB UPSC diagnosed from 1/1980 to 12/2011. Study inclusion required hysterectomy, salpingo-oophorectomy and negative chest imaging. Disease-free (DFS) and overall (OS) survival rates were calculated using the Kaplan-Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazards. RESULTS: Median age at diagnosis was 70 years (range, 53-87). Optimal cytoreduction (Opt) to <1cm residual disease was performed in 36 patients (75%). With a median follow-up of 21 months for all patients and 99 months for survivors, 36 (75%) experienced disease progression or relapse, most commonly intraperitoneal (16, 44%). At 5 years, DFS and OS rates were 12% and 19%, respectively. Five patients (10%) were long-term survivors without relapse at a median of 124 months. All 5 had Opt and carboplatin/paclitaxel chemotherapy, and 4 received radiotherapy (2 pelvic, 1 whole-abdominal, 1 brachytherapy). On MVA in the chemotherapy-treated population, Opt (HR 0.09, 95% CI 0.02-0.35) and radiotherapy (HR 0.36, 0.15-0.80) were associated with decreased rates of recurrence or progression. Opt (HR 0.09, 0.02 0.38) was prognostic for OS when adjusted for age. CONCLUSIONS: Clinical predictors of long-term survival for Stage IVB UPSC confined to the abdomen include optimal cytoreduction and adjuvant platinum and paclitaxel chemotherapy. Radiotherapy may decrease rates of recurrence or progression. Despite intra abdominal involvement, disease remission and long-term survival may be achieved in some patients. PMID- 24211402 TI - Serum HE4 as a prognostic marker in endometrial cancer--a population based study. AB - OBJECTIVE: HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. METHODS: Peri operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann-Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression analyses. RESULTS: Median CA125 and HE4 levels were higher in stage III and IV tumours (p<0.001) and in tumours with outer-half myometrial invasion (p<0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC)=0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC=0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR=2.40, 95% CI 1.19-4.83, p=0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR=2.86, 95% CI 1.25-6.51, p=0.012). CONCLUSION: These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy. PMID- 24211403 TI - Venomics of New World pit vipers: genus-wide comparisons of venom proteomes across Agkistrodon. AB - We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes. BIOLOGICAL SIGNIFICANCE: A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across Agkistrodon and a ground for understanding the natural histories of, and clinical observations of envenomations by, species of this genus. PMID- 24211404 TI - Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis. AB - Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), the most frequent cause of end-stage renal disease (ESRD). Exosomes isolated from urine are considered a rich non-invasive source of markers for renal events. Proteinuria associated with DN patients at advanced stages may result in "contamination" of exosomal fraction by co-precipitation of high abundance urine proteins, making it enormously difficult to obtain a reliable comparison of healthy individuals and DN patients and to detect minor proteins. We evaluated different protocols for urinary exosome isolation (ultracentrifugation-based and Exoquick(r) reagent-based) in combination with an easy and quick depletion procedure of contaminating high abundance proteins (albumin). The optimal methodology was then applied to investigate the proteome of human urinary exosomes in DN and controls using spectral counting LC-MS/MS analysis followed by selected reaction monitoring (SRM) confirmation. A panel of 3 proteins (AMBP, MLL3, and VDAC1) is differentially present in urinary exosomes from DN patients, opening a new field of research focused on improving diagnosis and follow-up of this pathology. BIOLOGICAL SIGNIFICANCE: Diabetic nephropathy (DN) is a progressive proteinuric kidney disease, a major complication of diabetes mellitus, and the most frequent cause of end-stage renal disease. Current markers of disease (i.e. creatinine and urinary albumin excretion) have proven limitations (i.e. some patients regress to normoalbuminuria, kidney damage may be already present in recently diagnoses microalbuminuric patients and renal function may decrease in the absence of significant albuminuria). We show here the first study on human DN proteome of urinary exosomes. Proteinuria associated to DN patients resulting in contamination of exosomal fraction and the associated difficulty to reliably compare healthy and disease conditions, are here overcome. A combined methodology pointed to increase exosomal proteome recovery and depletion of high-abundance proteome was here set-up. A total of 352 proteins were here identified for the first time associated to human urinary exosomes. Label-free quantitative comparison of DN urinary exosomes vs control group and SRM further validation, resulted in the discovery of a panel of three proteins (AMBP, MLL3 and VDAC1) which changes in DN, opening a new field of research focused to improve diagnosis and follow-up of this pathology. PMID- 24211405 TI - Initial description of the developing soybean seed protein Lys-N(epsilon) acetylome. AB - Characterization of the myriad protein posttranslational modifications (PTM) is a key aspect of proteome profiling. While there have been previous studies of the developing soybean seed phospho-proteome, herein we present the first analysis of non-histone lysine-N(E)-acetylation in this system. In recent years there have been reports that lysine acetylation is widespread, affecting thousands of proteins in diverse species from bacteria to mammals. Recently preliminary descriptions of the protein lysine acetylome from the plants Arabidopsis thaliana and Vitis vinifera have been reported. Using a combination of immunoenrichment and mass spectrometry-based techniques, we have identified over 400 sites of lysine acetylation in 245 proteins from developing soybean (Glycine max (L.) Merr., cv. Jack) seeds, which substantially increases the number of known plant N(E)-lysine-acetylation sites. Results of functional annotation indicate acetyl proteins are involved with a host of cellular activities. In addition to histones, and other proteins involved in RNA synthesis and processing, acetyl proteins participate in signaling, protein folding, and a plethora of metabolic processes. Results from in silico localization indicate that lysine-acetylated proteins are present in all major subcellular compartments. In toto, our results establish developing soybean seeds as a physiologically distinct addendum to Arabidopsis thaliana seedlings for functional analysis of protein Lys-N(E) acetylation. BIOLOGICAL SIGNIFICANCE: Several modes of peptide fragmentation and database search algorithms are incorporated to identify, for the first time, sites of lysine acetylation on a plethora of proteins from developing soybean seeds. The contributions of distinct techniques to achieve increased coverage of the lysine acetylome are compared, providing insight to their respective benefits. Acetyl-proteins and specific acetylation sites are characterized, revealing intriguing similarities as well as differences with those previously identified in other plant and non-plant species. PMID- 24211407 TI - Kinetic and thermodynamic investigation of enzymatic L-ascorbyl acetate synthesis. AB - Kinetics and thermodynamics of lipase-catalyzed esterification of l-ascorbic acid in acetone were investigated by using vinyl acetate as acyl donor. The results showed that l-ascorbic acid could generate inhibition effect on lipase activity. A suitable model, Ping-Pong Bi-Bi mechanism having substrate inhibition, was thus introduced to describe the enzymatic kinetics. Furthermore, the kinetic and thermodynamic parameters were calculated from a series of experimental data according to the kinetic model. The inhibition constant of L-ascorbic acid was also obtained, which seemed to imply that enhancing reaction temperature could depress the substrate inhibition. Besides, the activation energy values of the first-step and the second-step reaction were estimated to be 37.31 and 4.94 kJ/mol, respectively, demonstrating that the first-step reaction was the rate limiting reaction and could be easily improved by enhancing temperature. PMID- 24211406 TI - Phosphoproteome analysis reveals differences in phosphosite profiles between tumorigenic and non-tumorigenic epithelial cells. AB - Oral cancer disease represents a significant fraction of all human cancer types and its poor early diagnosis contributes to reduced individual survival rate. The identification of proteins modulated in tumorigenic cells and its post translational modifications may improve our understanding of tumor development in epithelial cells. We have analyzed the phosphoproteome of tumorigenic (SCC-9) and non-tumorigenic (HaCaT) cell lines using MS-based approach in order to identify phosphopeptides with differing patterns of modifications and/or abundance. Our results revealed the identity of 4,206 protein phosphorylation sites with sixty two sites showing to be significantly modulated between the two cell lines. The phosphoproteome data showed an overrepresentation of proteins with a possible role in nuclear regulatory functions. Pathway analysis was further performed on the phosphoproteome dataset and differences and commonalities of the functional pathways present in tumorigenic and non-tumorigenic cells were identified. Phosphopeptides that belong to the proteins lamina-associated polypeptide 2 isoform alpha and serine-arginine repetitive matrix protein 2 were identified with differential abundance and they appear as promising tumor-related phosphopeptides. These two proteins may be related to the structural alterations generally found in the nucleus of tumorigenic cells. The identification of phosphorylation sites in tumorigenic cells may contribute to disclose novel signaling mechanisms associated with OSCC. SIGNIFICANCE: Oral Squamous Cell Carcinoma (OSCC) is an important cancer disease affecting thousands of people worldwide. Many cellular processes related to the development of oral cancer remain unknown; however, the studies performed in vitro with cancer cells have contributed to guide more specific research which may be further performed by using in vivo approaches or clinical samples. To our knowledge, only few studies have been published showing the results of phosphoproteome profiling of squamous cell carcinoma models, and many signaling proteins must be identified and functionally characterized in order to increase the knowledge available about the complexity of the signaling networks responsible for oral cancer development and its progression. Furthermore, our knowledge regarding proteins exclusive or very low abundant in cancer cells remains limited. A better understanding of the differences between signaling pathways present in epithelial cell lines may contribute to reveal the processes underlying the OSCC. PMID- 24211408 TI - Tamavidin 2-HOT, a highly thermostable biotin-binding protein. AB - Tamavidin 2 is a fungal tetrameric protein that binds with high affinity to biotin, like avidin and streptavidin. We replaced asparagine-115, which lies in a subunit-subunit interface of tamavidin 2, with cysteine to generate the novel, highly thermostable protein tamavidin 2-HOT. Tamavidin 2-HOT retained more than 80% of its biotin-binding activity even after incubation at 99.9 degrees C for 60min and was fully active in 70% dimethylsulfoxide for 30min, whereas in these harsh conditions, avidin, streptavidin, and tamavidin 2 lost their activities (less than 20% of their biotin-binding activities). The Tm in which the biotin binding activity becomes half of tamavidin 2-HOT was 105 degrees C, at least 20 degrees C higher than those of avidin, streptavidin, and tamavidin 2. Because a reducing agent removed the thermal stability of tamavidin 2-HOT, the N115C mutation likely created disulfide bridges that stabilized inter-subunit associations. Tamavidin 2-HOT is efficiently produced in the soluble form by Escherichia coli for practical use. The isoelectric point of tamavidin 2-HOT (7.4) is sufficiently low to reduce the chance for non-specific binding of non target molecules due to high positive charges. Therefore, tamavidin 2-HOT may be useful in diverse novel applications that take advantage of its high biotin binding capability that can withstand harsh conditions. PMID- 24211409 TI - Deep venous thrombosis after saphenous endovenous radiofrequency ablation: is it predictable? AB - BACKGROUND: Endovenous radiofrequency ablation (RFA) is a safe and effective treatment for varicose veins caused by saphenous reflux. Deep venous thrombosis (DVT) is a known complication of this procedure. The purpose of this study is to describe the frequency of DVT after RFA and the associated predisposing factors. METHODS: A retrospective analysis was performed using prospectively collected data from December 2008 to December 2011; a total of 277 consecutive office-based RFA procedures were performed at a single institution using the VNUS ClosureFast catheter (VNUS Medical Technologies, San Jose, CA). Duplex ultrasonography scans were completed 2 weeks postprocedure in all patients. Risk factors assessed for the development of DVT included: great versus small saphenous vein (SSV) treated, right versus left side treated, number of radiofrequency cycles used, hypercoagulable state, history of DVT, tobacco use, medications (i.e., oral contraceptives, aspirin, warfarin, and clopidogrel), and vein diameter at the junction of the superficial and deep systems. RESULTS: Seventy-two percent of the patients were women, 56% were treated on the right side, and 86% were performed on the great saphenous vein (GSV). The mean age was 54 +/- 14 years (range: 23-88 years). Three percent of patients had a preprocedure diagnosis of hypercoagulable state, and 8% had a history of previous DVT. On postprocedural ultrasound, thrombus protrusion into the deep system without occlusion (endovenous heat induced thrombosis) was present in 11 patients (4%). DVT, as defined by thrombus protrusion with complete occlusion of the femoral or popliteal vein, was identified in 2 patients (0.7%). Previous DVT was the only factor associated with postprocedural DVT (P = 0.018). Although not statistically significant, there was a trend toward a higher risk of DVT in SSV-treated patients. Factors associated with endovascular heat-induced thrombosis alone were male sex (P = 0.02), SSV treatment (P = 0.05), aspirin use (P = 0.008), and factor V Leiden deficiency (P = 0.01). CONCLUSIONS: The use of RFA to treat patients with symptoms caused by saphenous reflux involves a small but definite risk of DVT. This study shows that the risk of post-RFA DVT is greater in patients with previous DVT, with a trend toward an increased risk in patients having treatment of the SSV. Periprocedural anticoagulation may be considered in this subset to reduce the risk of DVT after RFA. Thrombus protrusion without DVT was found to be more likely in patients with hypercoagulability, male sex, SSV treatment, and aspirin use. Additional prospective studies are required to analyze these and other factors that may predict thrombotic events after endovenous RFA. PMID- 24211410 TI - Usefulness of 18F-fluorodeoxyglucose positron emission tomography scan in the assessment of periprosthetic collections: report of 2 cases with opposite management. AB - Vascular prosthetic infection is a rare but serious complication of vascular surgery that requires rapid diagnosis and treatment. It is associated with high rates of amputation and death. The diagnosis is difficult when faced with a chronic nonspecific clinical presentation. We report 2 cases showing the diagnostic usefulness of positron emission tomography (PET). In 1 case, PET excluded with certainty the septic character of a periprosthetic collection fistulized with the skin by showing a periprosthetic fixation insufficient to diagnose an infection. In the other case, it confirmed the prosthetic infection in association with an evocative clinical picture by revealing a pathologic periprosthetic hyperfixation. PET scan therefore drew aside the diagnosis of prosthetic infection faced with a mild clinical and paraclinical presentation in the first case, and made it possible to pose it with certainty in the second case. This examination made it possible to save valuable time in 1 case and to elucidate the periprosthetic collection in the other case. Therefore, the rule of surgical explantation of any prosthesis with flow or periprosthetic collection is no more univocal. PMID- 24211411 TI - Isolated spontaneous renal artery dissection: endovascular management. AB - We report a rare case of isolated spontaneous renal artery dissection treated by stent placement. A 59-year-old man presented with a sudden onset of left flank pain and severe hypertension together with elevated creatinine levels. A computed tomography scan revealed a focal dissection at the left renal artery (LRA) with an infarcted left kidney. Despite medical treatment with 4 drugs, the patient's blood pressure remained uncontrolled. Angiography confirmed the diagnosis. A 6- * 60-mm Xpert stent (Abbott Vascular, Temecula, CA) was deployed at the LRA, achieving an enlarged true lumen with a patent stent. After the procedure, acute renal impairment was observed but pain subsided and blood pressure normalized under the treatment prescribed. At 12 months of follow-up, the patient was normotensive and asymptomatic with mild chronic renal failure and a patent LRA stent on doppler ultrasonography. The endovascular treatment of isolated spontaneous renal artery dissection appears to be feasible and effective and could be the first-line treatment when revascularization is needed. PMID- 24211412 TI - Spontaneous pseudoaneurysm of the hand. AB - Pseudoaneurysm of the hand is rare. Few cases have been reported in the literature, and these cases are usually related to trauma. Early treatment is recommended for pseudoaneurysm after it has been diagnosed. We report the surgical treatment of spontaneous pseudoaneurysm of the hand in a patient who was undergoing anticoagulant therapy. PMID- 24211413 TI - Methods of biological network inference for reverse engineering cancer chemoresistance mechanisms. AB - We review recent Bayesian network inference methodologies we developed to infer genetic and metabolic pathways associated to oncological drug chemoresistance. Bayesian inference is supported by a rigorous and widely accepted mathematical formalization of predictive analytics. It is an inherently integrative approach allowing the incorporation of prior knowledge and constraints. Moreover, it is recommended to treat noisy data, and large amount of data whose dynamics laws are mostly unknown. We focus on variational Bayesian methods for the inference of stochastic reaction processes and we present a compendium of the recent results of inference of gene and metabolic networks presiding at the development of pancreas cancer resistance to gemcitabine. PMID- 24211414 TI - Detection of viral and bacterial pathogens in acute respiratory infections. AB - OBJECTIVES: The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. METHODS: Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenzae(HI), Moraxella catarrhalis(MC) and Streptococcus pneumoniae(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI severity. RESULTS: Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI = 28%, MC = 14%, SP = 7%) compared to specimens from healthy adults (5% overall; HI = 0%, MC = 2.5%, SP = 2.5%; p < 0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%; p = 0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. CONCLUSION: Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. PMID- 24211415 TI - OprD mutations and inactivation in imipenem-resistant Pseudomonas aeruginosa isolates from China. AB - To investigate the mechanisms involved in imipenem resistance of Pseudomonas aeruginosa in southern China, 61 imipenem-resistant P. aeruginosa clinical isolates were collected from 4 hospitals between October 2011 and June 2012. All isolates were resistant to imipenem, whereas 21.3% were susceptible or intermediate to meropenem. Variable degrees of resistance to other beta-lactam and non-beta-lactam antimicrobials were observed. PFGE revealed high-level of clonal diversity. Among the 61 isolates, 50 isolates had OprD loss by disrupted oprD mutations, including 43 with frameshift mutations of oprD and 7 with a premature stop codon by single point mutation. Six isolates were oprD-negative by PCR, suggestive of a major disruption of oprD genes. Five isolates had intact oprD but had reduced expression of oprD genes. In addition, only one isolate with disrupted oprD mutation by a premature stop codon was confirmed to be a metallo beta-lactamase producer (IMP-9). Our results show that the loss of OprD, as well as reduced expression of oprD and MBL production, were the predominant mechanisms of imipenem resistance in P. aeruginosa in southern China. PMID- 24211416 TI - Preparation, characterization and pharmacokinetics of Amoitone B-loaded long circulating nanostructured lipid carriers. AB - Amoitone B, chemically synthesized as the derivative of Cytosporone B, is a powerful agonist for Nur77 receptor. It has outstanding anticancer activity in vivo. However, the water-insolubility and short biological half-life lead to poor bioavailability, which limits its application. The aim of this study was to develop polyethylene glycol-coated Amoitone B-loaded nanostructured lipid carriers (AmB-PEG-NLC) for parenteral delivery of Amoitone B to prolong drug circulation time in body and enhance the bioavailability. AmB-PEG-NLC were prepared by emulsion-evaporation and low temperature-solidification method, while Amoitone B-loaded NLC (AmB-NLC) were also prepared as control. The characteristics of AmB-PEG-NLC and AmB-NLC such as particle size, zeta potential, entrapment efficiency and drug loading were investigated in detail. The mean particle size was about 200 nm and the zeta potential value was about -15 mV. The X-ray diffraction analysis demonstrated that Amoitone B was not in crystalline state in NLC (AmB-PEG-NLC and AmB-NLC). Drug release pattern with burst release initially and prolonged release afterwards was obtained in vitro for AmB-PEG-NLC. Furthermore, AmB-PEG-NLC exhibited prolonged MRT (mean residence time) and higher AUC (area under drug concentration-time curve) compared with AmB-NLC as well as Amoitone B solution. These results indicated that AmB-PEG-NLC could be a promising delivery system for Amoitone B to prolong the circulation time in body and thus improve its bioavailability. PMID- 24211417 TI - Effect of particle size on conformation and enzymatic activity of EcoRI adsorbed on CdS nanoparticles. AB - Better understanding of the interaction between nanoparticles (NPs) and protein is the basis for biological and biomedical applications of NPs. Water-soluble fluorescent CdS NPs have been widely used in the biological and biomedical fields and the study on effect of CdS NPs size on conformation and enzymatic activity of protein might be very important in its application. In this work, the interaction of CdS NPs with different size with type II restriction endonuclease (EcoRI) were investigated by atomic force microscopy, transmission electron microscopy, UV-vis spectroscopy, fluorescence quenching method, CD spectra, laser scanning confocal microscopy and gel electrophoresis. It was found that the equilibrium constant (kD) as well as the cooperativity degree of CdS NPs-EcoRI binding (Hill constant, n) strongly depended on the CdS NPs size. The different curvature of CdS NPs surface could result in different changes of EcoRI conformation. The gel electrophoresis indicated that the decrease in alpha-helix content more or less affected the activity of EcoRI. PMID- 24211418 TI - Morphometric changes in C57BL/6 mice retina infected by Toxoplasma gondii ME 49 strain. AB - This study evaluated the morphometric implications in C57BL/6 mouse retina infected by Toxoplasma gondii, ME 49 strain. Twenty C57BL/6 female mice were divided into group 1 (n=8, intraperitoneally infected with 30 cysts of T. gondii ME 49 strain) and group 2 (n=12 non-infected controls). The eyes were enucleated on the 60th day after infection, fixed and processed for light microscopy. Changes in retinal thickness and in the perimeter/area ratio (P/A) of the retinal layers were analyzed by digital morphometry. We considered that P/A was the measurement of retinal architecture distortion induced by toxoplasmosis. This study considered the ganglion cells and nerve fiber layers as a monolayer, thus six layers of retina were evaluated: photoreceptors (PRL), outer nuclear (ONL), outer plexiform (OPL), inner nuclear (INL), inner plexiform (IPL) and ganglion cells/nerve fiber monolayer (GNL). Histological analysis of infected mouse retina showed inflammatory infiltrate, necrosis, glial reaction and distortion of the retina architecture. It also presented increased thickness (167.8+/-24.9MUm versus 121.1+/-15.4MUm, in controls) and increased retinal thickness within the retinitis foci (187.7+/-16.6MUm versus 147.9+/-12.2MUm out of the retinitis foci). A statistically significant difference in P/A was observed between infected and uninfected mouse retinas. The same was observed in PRL, OPL, INL and GNL. Retinal morphometry may be used to demonstrate differences between infected and uninfected mouse retinas. PMID- 24211419 TI - Efficacy of an anthelmintic combination in sheep infected with Fasciola hepatica resistant to albendazole and clorsulon. AB - In the current study, we identified five sheep flocks with fasciolosis in the province of Leon (northwestern Spain) in order to determine the anthelmintic resistance status to three commonly used anthelmintics, namely albendazole (ABZ), triclabendazole (TCBZ) and clorsulon (CLOR). The identification of one flock resistant to ABZ and CLOR was shown after the faecal egg count reduction test (FECRT). The reductions in eggs per gram values were -17.6% and -68% against immature and adult flukes, respectively, after ABZ treatment; 85.15% and 44.91% against immature and adult flukes, respectively, after CLOR treatment; and 97.06% against both stages, after the administration of TCBZ. As an alternative to control the infection, two combinations of ABZ and CLOR were tested. In the first, both drugs were administered at the recommended dose of each; in this case, the efficiency reached values above 95% against both immature and adult flukes. However, when the combined drugs were administered at half the recommended dose of each, the efficiency of the combination was very low, i.e. 16.67% and -11.11% against mature and immature flukes, respectively. In conclusion, this preliminary report suggests a possible interaction between ABZ and CLOR after their joint administration. However, these results should be confirmed in other flocks. PMID- 24211420 TI - Repression of Smad7 mediated by DNMT1 determines hepatic stellate cell activation and liver fibrosis in rats. AB - Conversion of hepatic stellate cells (HSCs) into hepatic myofibroblasts is a necessary event during the development of liver fibrosis. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of profibrotic genes, is selectively induced in myofibroblasts from diseased livers. Treatment of HSC with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-azadC), prevented TGF-beta1-induced proliferation and alpha-smooth muscle actin (alpha-SMA) and collagen expression. 5-AzadC also rescued TGF-beta1-induced suppression of Smad7 expression which occurs during HSC activation. Similarly, silencing the expression of the DNMT1 gene ameliorated the suppression of Smad7 expression by TGF-beta1. In addition, DNMT1 inhibition, by 5-azadC or DNMT1 silencing, prevented the phosphorylation of Smad2 and Smad3. These studies suggest that epigenetic repression of Smad7 promotes the phosphorylation of Smad2 and Smad3 that may be an important molecular mechanism for perpetuated HSC activation and liver fibrosis. PMID- 24211421 TI - The role of NAD(+)-dependent isocitrate dehydrogenase 3 subunit alpha in AFB1 induced liver lesion. AB - Aflatoxin B1 (AFB1) is a potent hepatocarcinogen that causes carcinogenesis in many animal species. In previous study, we found that isocitrate dehydrogenase 3alpha subunit (IDH3alpha) was upregulated in AFB1-induced carcinogenesis process. In this study, the sequences of IDH3alpha from various species were compared and the protein expression levels in different organs were examined, and the results showed that IDH3alpha was a widely distributed protein and shared highly conserved sequence in various species. In the same time, IDH3alpha was demonstrated to accumulate in a dose-dependent manner induced by AFB1 in cells, and was also up-regulated in the process of AFB1-induced liver lesion. Similar results were observed when H2O2 was used to replace AFB1. Over-expression of IDH3alpha increased the phosphorylation level of Akt (Protein kinase B) and neutralized the cellular toxicity induced by AFB1 or H2O2 and apoptosis induced by AFB1, while the reduced expression of IDH3alpha by siRNA decreased the phosphorylation, indicating that IDH3alpha played important roles in oxidative stress-induced PI3K/Akt pathway. Overall, the results suggested that AFB1 treatment could increase the expression of IDH3alpha, and the activated PI3K/Akt pathway by IDH3alpha eventually neutralized the apoptosis induced by AFB1. PMID- 24211422 TI - Bioactivation to an aldehyde metabolite--possible role in the onset of toxicity induced by the anti-HIV drug abacavir. AB - Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species. Abacavir is one of the options for combined anti-HIV therapy. Although individual susceptibilities to adverse effects differ among patients, abacavir is associated with idiosyncratic hypersensitivity drug reactions and an increased risk of cardiac dysfunction. This review highlights the current knowledge on abacavir metabolism and discusses the potential role of bioactivation to an aldehyde metabolite, capable of forming protein adducts, in the onset of abacavir-induced toxic outcomes. PMID- 24211423 TI - Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway. AB - Oxidative stress caused by doxorubicin (DOX) is believed to be a major underlying molecular mechanism of DOX-induced cardiotoxicity. Sesamin (Ses), an active component extracted from sesame seeds, exhibits antioxidative and anti inflammatory effects. In the present study, possible protective mechanisms of Ses on DOX-induced cardiotoxicity were investigated in rats and cultured H9C2 cells. We demonstrated that Ses exhibits a significant protective effect on cardiac tissue in animal and cell models of DOX-induced cardiac injury. Moreover, Ses can ameliorate DOX-induced oxidative stress and mitochondrial damage. Further studies suggested that Ses is able to up-regulate the protein expression of Mn-SOD in normal rats and to restore the decreased expression of Mn-SOD in DOX-induced cardiac injury rats. Exposure to Ses or DOX alone slightly increased the protein expression of Sirt1; however, a more remarkable increase in Sirt1 protein level was detected in the Ses+DOX group. Treatment with a pan-sirtuin inhibitor (nicotinamide) or a Sirt1-specific inhibitor (EX-527) partially antagonised the effect of Ses on DOX-induced mitochondrial damage and completely abolished the effect of Ses on Mn-SOD expression. These findings indicate that the protective mechanisms of Ses on DOX-induced cardiotoxicity are involved in the alleviation of oxidative stress injury and Mn-SOD dysfunction, partially via the activation of Sirt1. PMID- 24211424 TI - Interactions between the entomopathogenic nematode Heterorhabditis sonorensis (Nematoda: Heterorhabditidae) and the saprobic fungus Fusarium oxysporum (Ascomycota: Hypocreales). AB - In this study, we assessed the effect of the saprobic fungus, Fusarium oxysporum (Ascomycota: Hypocreales) on the fitness of the entomopathogenic nematode Heterorhabditis sonorensis (Caborca strain). Sand column assays were considered to evaluate the effect of fungal mycelia on infective juvenile (IJ) movement and host access. Additionally, we investigated the effect of fungal spores on the nematodes' ability to search for a host, its virulence, penetration efficiency and reproduction. Three application timings were considered to assess interactions between the fungus and the nematodes. In vitro assays were also considered to determine the effect of fungal extracts on the nematode's symbiotic bacteria. Our observations indicate that presence and age of fungal mycelia significantly affect IJ movement in the sand columns and their ability to establish in the host. These results were also reflected in a reduced insect mortality. In particular, treatments with the 15 days old mycelia showed a significant reduction in insect mortality and penetration efficiency. Presence of fungal spores also impacted nematode virulence and reproduction. In particular, two of the application timings tested (simultaneous [EPN and fungal spores applied at the same time] and alternate I [EPN applied first, fungus applied 24h later]) resulted in antagonistic interactions. Moreover, IJ progeny was reduced to half in the simultaneous application. In vitro assays revealed that fungal extracts at the highest concentration tested (10mg/ml) inhibited the growth of the symbiotic bacteria. Overall, these results suggest that saprobic fungi may play an important role in regulating. EPN populations in the soil, and that they may be one of the factors that impact nematode survival in the soil and their access to insect hosts. PMID- 24211425 TI - Mitochondrial DNA integrity changes with age but does not correlate with learning performance in honey bees. AB - The honey bee is a well-established model organism to study aging, learning and memory. Here, we used young and old forager honey bees to investigate whether age related learning capacity correlates with mitochondrial function. The bees were selected for age and learning performance and mitochondrial function was evaluated by measuring mtDNA integrity, mtDNA copy number and mitochondrial gene expression. Quite unexpectedly, mtDNA from young bees showed more damage than mtDNA from older bees, but neither mtDNA integrity, nor mtDNA copy number nor mitochondrial gene expression correlated with learning performance. Although not statistically significant (p=0.07) the level of L-rRNA increased with age in good learners whereas it decreased in poor learners. Our results show that learning performance in honey bee does not correlate with absolute mitochondrial parameters like mtDNA damage, copy number or expression of mitochondrial genes, but may be associated with the ability to regulate mitochondrial activity. PMID- 24211426 TI - Caloric restriction and aging stem cells: the stick and the carrot? AB - Adult tissue stem cells have the ability to adjust to environmental changes and affect also the proliferation of neighboring cells, with important consequences on tissue maintenance and regeneration. Stem cell renewal and proliferation is strongly regulated during aging of the organism. Caloric restriction is the most powerful anti-aging strategy conserved throughout evolution in the animal kingdom. Recent studies relate the properties of caloric restriction to its ability in reprogramming stem-like cell states and in prolonging the capacity of stem cells to self-renew, proliferate, differentiate, and replace cells in several adult tissues. However this general paradigm presents with exceptions. The scope of this review is to highlight how caloric restriction impacts on diverse stem cell compartments and, by doing so, might differentially delay aging in the tissues of lower and higher organisms. PMID- 24211427 TI - Bisphosphonate-osteoclasts: changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients. AB - Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6+/-11.5yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant osteoclasts" with increased size, numerous nuclei (>10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen containing bisphosphonates, thus being clearly distinguishable from giant osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover. PMID- 24211428 TI - A sulfuric-lactic acid process for efficient purification of fungal chitosan with intact molecular weight. AB - The most recent method of fungal chitosan purification, i.e., two steps of dilute sulfuric acid treatment, pretreatment of cell wall at room temperature for phosphate removal and extraction of chitosan from the phosphate free cell wall at high temperature, significantly reduces the chitosan molecular weight. This study was aimed at improvement of this method. In the pretreatment step, to choose the best conditions, cell wall of Rhizopus oryzae, containing 9% phosphate, 10% glucosamine, and 21% N-acetyl glucosamine, was treated with sulfuric, lactic, acetic, nitric, or hydrochloric acid, at room temperature. Sulfuric acid showed the best performance in phosphate removal (90%) and cell wall recovery (89%). To avoid depolymerisation of chitosan, hot sulfuric acid extraction was replaced with lactic acid treatment at room temperature, and a pure fungal chitosan was obtained (0.12 g/g cell wall). Similar pretreatment and extraction processes were conducted on pure shrimp chitosan and resulted in a chitosan recovery of higher than 87% while the reduction of chitosan viscosity was less than 15%. Therefore, the sulfuric-lactic acid method purified the fungal chitosan without significant molecular weight manipulation. PMID- 24211429 TI - Composition and antioxidant activity of polysaccharides from jujuba by classical and ultrasound extraction. AB - Crude Zizyphus Jujuba cv. Junzao polysaccharides (CZP) were extracted by hot water and ultrasound-assisted extraction respectively. Using a short application of ultrasound, the yield of polysaccharides increased from 6.23 to 7.95%, which represents an increase of about 27.6%. Both CZPU and CZPH were composed of arabinose, rhamnose, glucose, galactose, and mannose. However, the molar ratio of CZPU was 5.46: 4.96: 5.17: 2.63: 1, while it was 5.46: 4.89: 3.65: 2.54: 1 for CZPH. Furthermore, CZPU had stronger antioxidant activities than CZPH by evaluating in hydroxyl radical and ferric-reducing antioxidant power (FRAP) assay. PMID- 24211430 TI - Synthesis and characterization of some novel antimicrobial thiosemicarbazone O carboxymethyl chitosan derivatives. AB - Three novel thiosemicarbazone O-carboxymethyl chitosan derivatives were obtained via a condensation reaction of thiosemicarbazide O-carboxymethyl chitosan with o hydroxybenzaldehyde, p-methoxybenzaldehyde, and p- chlorobenzaldehyde respectively. Their structures were characterized by elemental analysis, FTIR, (13)C NMR and X-ray diffraction. The antimicrobial behaviors of the prepared derivatives against three types of bacteria Staphylococcus aureus (S. aureus, RCMBA 2004), Bacillus subtilis (B. subtilis, RCMBA 6005), and Escherichia coli (E. Coli, RCMBA 5003) and three crops-threatening pathogenic fungi Aspergillus fumigatus (A. fumigatus, RCMBA 06002), Geotrichum candidum (G. candidum, RCMB 05098), and Candida albicans (C. albicans, RCMB 05035) were investigated. The results indicated that the antibacterial and antifungal activities of the investigated derivatives are much higher than those of the parent O-carboxymethyl chitosan. They were more potent in case of Gram-positive bacteria than Gram negative bacteria. The presence of electron withdrawing chlorine atom on the aryl moiety of the aldehyde portion improved greatly antimicrobial activity to be nearly equivalent to the used standard drugs. PMID- 24211432 TI - Amidase encapsulated O-carboxymethyl chitosan nanoparticles for vaccine delivery. AB - This work reports the development of amidase encapsulated O-carboxymethyl chitosan nanoparticles (Ami-O-CMC NPs) of 300+/-50 nm size by ionic cross-linking method. The prepared Ami-O-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against Staphylococcus aureus infections. PMID- 24211431 TI - In vitro assessment of agave fructans (Agave salmiana) as prebiotics and immune system activators. AB - The prebiotic effect of agave fructans (Agave salmiana) was evaluated through the growth of two lactic acid bacterial (LAB) strains (Lactobacillus casei and Bifidobacterium lactis). The immune system was activated through the stimulation of peripheral blood mononuclear cells (PBMC) of healthy subjects testing fructans, LAB or a mixture of these compounds at different concentrations. Immune responses, such as early cell activation (CD69), cell cycle progression, nitric oxide (NO) production and the expression of transcription factors for lymphocyte differentiation, were analyzed. Compared with other fructans, the extracted agave fructans showed the highest prebiotic activity and increased levels of CD69 expression, proliferative activity and NO production when administered with the probiotic L. casei. The Th1 lymphocyte differentiation produced through LAB stimulation was greatly diminished after the incorporation of agave fructans. In conclusion, these types of fructans (A. salmiana) are involved in the activation and selective differentiation of cells of the immune system through interactions with probiotics. Thus, agave fructans represent a novel immunomodulator that might benefit the functional food industry. PMID- 24211433 TI - Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery. AB - Poly(N-acryloyl glycinamide) is a neutral polymer that can form gel-sol thermoresponsive systems with upper critical solution temperature in aqueous media. The temperature of the reversible gel-sol transition depends on the molar mass and the concentration of macromolecules. These parameters were combined to adjust the transition temperature slightly above body temperature for the sake of respecting living tissues during the sol form injection using a classical syringe. On contact with local tissues, the injected sol turned rapidly to a gel. The simplicity of the process makes it exploitable to administrate and deliver neutral or ionic drug and especially those that are soluble in aqueous media. The versatility was exemplified from formulations with cobalt acetate, small polymers (MW~2000g/mol), tartrazine and methylene blue dyes and albumin. The model compounds were allowed to diffuse in an isotonic pH=7.4 buffered medium at 37 degrees C. All the release profiles were typical of diffusion control with 100% release within 2 to 3weeks and no obvious burst. The in vitro release of methylene blue from a gel formulation was checked prior to injection in the peritoneal cavity of mice where the release of the dye was monitored visually through tissue and organ colorations. A comparable polymer-free dye solution was used as control. Coloration appeared rapidly in tissues and organs and it was still detectable 52h post injection of the gel whereas it was no longer present at 24h in control mice. PMID- 24211434 TI - Phosphorylation-related modification at the dimer interface of 14-3-3omega dramatically alters monomer interaction dynamics. AB - 14-3-3 proteins are generally believed to function as dimers in a broad range of eukaryotic signaling pathways. The consequences of altering dimer stability are not fully understood. Phosphorylation at Ser58 in the dimer interface of mammalian 14-3-3 isoforms has been reported to destabilise dimers. An equivalent residue, Ser62, is present across most Arabidopsis isoforms but the effects of phosphorylation have not been studied in plants. Here, we assessed the effects of phosphorylation at the dimer interface of Arabidopsis 14-3-3omega. Protein kinase A phosphorylated 14-3-3omega at Ser62 and also at a previously unreported residue, Ser67, resulting in a monomer-sized band on native-PAGE. Phosphorylation at Ser62 alone, or with additional Ser67 phosphorylation, was investigated using phosphomimetic versions of 14-3-3omega. In electrophoretic and chromatographic analyses, these mutants showed mobilities intermediate between dimers and monomers. Mobility was increased by detergents, by reducing protein concentration, or by increasing pH or temperature. Urea gradient gels showed complex structural transitions associated with alterations of dimer stability, including a previously unreported 14-3-3 aggregation phenomenon. Overall, our analyses showed that dimer interface modifications such as phosphorylation reduce dimer stability, dramatically affecting the monomer-dimer equilibrium and denaturation trajectory. These findings may have dramatic implications for 14-3-3 structure and function in vivo. PMID- 24211435 TI - RyR3 in situ regulation by Ca(2+) and quercetin and the RyR3-mediated Ca(2+) release flux in intact Jurkat cells. AB - Ryanodine receptors are generally thought to possess a high-affinity activating cytosolic Ca(2+) site and a low-affinity inhibitory cytosolic Ca(2+) site. By performing conformation selective measurements in which quercetin was used as a fluorescent marker for RyR3 (ryanodine receptor type 3) in Jurkat cells, we now find that the rectified RyR3 channel in open conformation may be regulated in situ by two cytosolic activating Ca(2+) sites, of low and high affinity, respectively, whereas no inhibitory Ca(2+) effect could be delineated. In the closed rectified channel, as well as in the open hindered channel, only the high affinity activating Ca(2+) site and the inhibitory Ca(2+) site were functional, whereas in the closed hindered channel all three regulatory Ca(2+) sites appeared to be operational. RyR3 also seems to possess one activating and two inhibitory quercetin sites. Corresponding Hill coefficients and affinities of these regulatory sites were estimated. Quercetin cellular uptake exhibited an initial rapid phase (~1.04 min), followed by slow accumulation of free quercetin inside the cytosol (~34.5 min). The RyR3-mediated Ca(2+) release current increased from a baseline of 247 to 287 pA in 1 min. after addition of 50 MUM quercetin and then declined slowly to a plateau of 265 pA. PMID- 24211436 TI - 4-Hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase: exemplars of the alpha-keto acid dependent oxygenases. AB - 4-Hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate synthase (HMS) are outliers within the alpha-keto acid dependent oxygenase (alphaKAO) family. HPPD and HMS catalyze the chemistry of the majority of enzymes within the alphaKAO family but are clearly mechanistically convergent, having a grossly different structural topology. Some of the unique characteristics of HPPD and HMS have elucidated select parts of the catalytic cycle that are obscured in other family members. Moreover, the inhibitory chemistry of HPPD is a phenomenon with ever-expanding relevance across all kingdoms of life. This review is a synopsis of the literature pertaining to HPPD and HMS. It is not intended as an exhaustive compilation of all observations made for these enzymes but rather a condensed narrative that connects those studies that have advanced the understanding of the chemistry of both enzymes. PMID- 24211437 TI - Gradient language dominance affects talker learning. AB - Traditional conceptions of spoken language assume that speech recognition and talker identification are computed separately. Neuropsychological and neuroimaging studies imply some separation between the two faculties, but recent perceptual studies suggest better talker recognition in familiar languages than unfamiliar languages. A familiar-language benefit in talker recognition potentially implies strong ties between the two domains. However, little is known about the nature of this language familiarity effect. The current study investigated the relationship between speech and talker processing by assessing bilingual and monolingual listeners' ability to learn voices as a function of language familiarity and age of acquisition. Two effects emerged. First, bilinguals learned to recognize talkers in their first language (Korean) more rapidly than they learned to recognize talkers in their second language (English), while English-speaking participants showed the opposite pattern (learning English talkers faster than Korean talkers). Second, bilinguals' learning rate for talkers in their second language (English) correlated with age of English acquisition. Taken together, these results suggest that language background materially affects talker encoding, implying a tight relationship between speech and talker representations. PMID- 24211438 TI - Evidence for a learning bias against saltatory phonological alternations. AB - This study provides new experimental evidence that people learn phonological alternations in a biased way. Adult participants were exposed to alternations between phonetically dissimilar sounds (i.e., those differing in both voicing and manner, such as [p] and [v]). After learning these alternations, participants assumed, without evidence in the input, that more similar sounds (e.g., [b] and [v]) also alternated (Exp. 1). Even when provided with explicit evidence that dissimilar sounds (e.g., [p] and [v]) alternated but similar sounds ([b] and [v]) did not, participants tended to make errors in assuming that the similar sounds also alternated (Exp. 2). By comparison, a control group of participants found it easier to learn the opposite pattern, where similar sounds alternated but dissimilar sounds did not. The results are taken as evidence that learners have a soft bias, considering alternations between perceptually similar sounds to be more likely. PMID- 24211439 TI - Preschoolers use pedagogical cues to guide radical reorganization of category knowledge. AB - In constructing a conceptual understanding of the world, children must actively evaluate what information is idiosyncratic or superficial, and what represents essential, defining information about kinds and categories. Preschoolers observed identical evidence about a novel object's function (magnetism) produced in subtly different manners: accidentally, intentionally, or demonstrated communicatively and pedagogically. Only when evidence was explicitly demonstrated for their benefit did children reliably go beyond salient perceptual features (color or shape), to infer function to be a defining property on which to base judgments about category membership. Children did not show this pattern when reasoning about a novel perceptual property, suggesting that a pedagogical communicative context may be especially important for children's learning about artifact functions. Observing functional evidence in a pedagogical context helps children construct fundamentally different conceptions of novel categories as defined not by superficial appearances but by deeper, functional properties. PMID- 24211441 TI - The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats. AB - Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring. PMID- 24211440 TI - Anatomically discrete sex differences and enhancement by testosterone of cell proliferation in the telencephalic ventricle zone of the adult canary brain. AB - Previous work in songbirds has suggested that testosterone increases neuronal recruitment and survival in HVC but does not affect neuronal proliferation in the ventricular zone and that males and females have similar rates of proliferation except at discrete locations. Many of these conclusions are however based on limited data or were inferred indirectly. Here we specifically tested the effects of testosterone on cellular proliferation in the ventricular zone of both male and female adult canaries. We implanted adult birds of both sexes with testosterone or empty implants for 1 week and injected them with BrdU. One day later, we collected their brains and quantified BrdU-positive cells in the ventricular zone (VZ) at different rostro-caudal levels of the brain, ranging from the level where the song nucleus Area X occurs through the caudal extent of HVC. Proliferation in the dorsal part of the VZ was low and unaffected by sex or testosterone treatment. In the ventral part of the VZ, females had more proliferating cells than males, but only at rostral levels, near Area X. Also in the ventral part of the VZ, testosterone increased proliferation in birds of both sexes, but only in the mid- to caudal-VZ, caudal to the level of Area X, around the septum and HVC. We thus demonstrate here that there is both an effect of testosterone and possibly a more subtle effect of sex on cellular proliferation in the adult songbird brain, and that these effects are specific to different levels of the brain. PMID- 24211442 TI - Exclusive induction of G:C to A:T transitions by 3-azido-1,2-propanediol in yeast. AB - Sodium azide is a strong mutagen which has been successfully employed in mutation breeding of crop plants. In biological systems, it is metabolized to azidoalanine, but further bioactivation to a putative ultimate mutagen as well as the nature of the induced DNA modifications leading to mutations remain elusive. In this study, mutations induced in the CAN1 gene of yeast Saccharomyces cerevisiae by the representative mutagen 3-azido-1,2-propanediol (azidoglycerol, AZG) have been sequenced. Analysis of the forward mutation spectrum to canavanine resistance revealed that AZG induced nearly exclusively G:C to A:T transitions. AZG also induced reversions to tryptophan prototrophy by base-pair substitutions in a dose-dependent manner. This unusual mutational specificity may be shared by other organic azido compounds. PMID- 24211443 TI - All-natural composite wound dressing films of essential oils encapsulated in sodium alginate with antimicrobial properties. AB - We present natural polymeric composite films made of essential oils (EOs) dispersed in sodium alginate (NaAlg) matrix, with remarkable anti-microbial and anti-fungal properties. Namely, elicriso italic, chamomile blue, cinnamon, lavender, tea tree, peppermint, eucalyptus, lemongrass and lemon oils were encapsulated in the films as potential active substances. Glycerol was used to induce plasticity and surfactants were added to improve the dispersion of EOs in the NaAlg matrix. The topography, chemical composition, mechanical properties, and humidity resistance of the films are presented analytically. Antimicrobial tests were conducted on films containing different percentages of EOs against Escherichia coli bacteria and Candida albicans fungi, and the films were characterized as effective or not. Such diverse types of essential oil-fortified alginate films can find many applications mainly as disposable wound dressings but also in food packaging, medical device protection and disinfection, and indoor air quality improvement materials, to name a few. PMID- 24211444 TI - Production of prone-to-aggregate proteins. AB - Expression of recombinant proteins in Escherichia coli (E. coli) remains the most popular and cost-effective method for producing proteins in basic research and for pharmaceutical applications. Despite accumulating experience and methodologies developed over the years, production of recombinant proteins prone to aggregate in E. coli-based systems poses a major challenge in most research applications. The challenge of manufacturing these proteins for pharmaceutical applications is even greater. This review will discuss effective methods to reduce and even prevent the formation of aggregates in the course of recombinant protein production. We will focus on important steps along the production path, which include cloning, expression, purification, concentration, and storage. PMID- 24211445 TI - Live-cell single-molecule imaging reveals clathrin and caveolin-1 dependent docking of SMAD4 at the cell membrane. AB - Transforming growth factor beta (TGF-beta) signaling is important for many biological processes. Although the sequential events of this cascade are known, the dynamics remain speculative. Here, live-cell single-molecule total internal reflection fluorescence microscopy was used to monitor the dynamics of SMAD4, a TGF-beta downstream effector, in MDA-MB-231 breast cancer cells. Contrary to previous belief, SMAD4 was detectable at the cytoplasmic membrane, displaying two subpopulations with different membrane docking behaviors. These subpopulations were regulated by clathrin and caveolin-1, and had opposing roles in the nuclear shuttling of SMAD4 and the subsequent transcriptional regulation of genes associated with cell migration. The notion that membrane-docking behaviors of downstream molecules could predict the cellular response to growth factors may revolutionize the way we view cell signaling. PMID- 24211447 TI - Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5' cap. AB - Initiation is the rate-limiting step during mRNA 5' cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition. PMID- 24211446 TI - Differential calmodulin-modulatory and electron transfer properties of neuronal nitric oxide synthase mu compared to the alpha variant. AB - Neuronal nitric oxide synthase MU (nNOSMU) contains 34 additional residues in an autoregulatory element compared to nNOSalpha. Cytochrome c and flavin reductions in the absence of calmodulin (CaM) were faster in nNOSMU than nNOSalpha, while rates in the presence of CaM were smaller. The magnitude of stimulation by CaM is thus notably lower in nNOSMU. No difference in NO production was observed, while electron transfer between the FMN and heme moieties and formation of an inhibitory ferrous-nitrosyl complex were slower in nNOSMU. Thus, the insert affects electron transfer rates, modulation of electron flow by CaM, and heme nitrosyl complex formation. PMID- 24211448 TI - Quality control of a molybdoenzyme by the Lon protease. AB - Molybdoenzymes contain a molybdenum cofactor in their active site to catalyze various redox reactions in all domains of life. To decipher crucial steps during their biogenesis, the TorA molybdoenzyme of Escherichia coli had played a major role to understand molybdoenzyme maturation process driven by specific chaperones. TorD, the specific chaperone of TorA, is also involved in TorA protection. Here, we show that immature TorA (apoTorA) is degraded in vivo and in vitro by the Lon protease. Lon interacts with apoTorA but not with holoTorA. Lon and TorD compete for apoTorA binding but TorD binding protects apoTorA against degradation. Lon is the first protease shown to eliminate an immature or misfolded molybdoenzyme probably by targeting its inactive catalytic site. PMID- 24211449 TI - Temporary inhibition of dorsal or ventral hippocampus by muscimol: distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning. AB - Studies in rats, involving hippocampal lesions and hippocampal drug infusions, have implicated the hippocampus in the modulation of anxiety-related behaviors and conditioned fear. The ventral hippocampus is considered to be more important for anxiety- and fear-related behaviors than the dorsal hippocampus. In the present study, we compared the role of dorsal and ventral hippocampus in innate anxiety and classical fear conditioning in Wistar rats, examining the effects of temporary pharmacological inhibition by the GABA-A agonist muscimol (0.5 ug/0.5 ul/side) in the elevated plus maze and on fear conditioning to a tone and the conditioning context. In the elevated plus maze, dorsal and ventral hippocampal muscimol caused distinct behavioral changes. The effects of ventral hippocampal muscimol were consistent with suppression of locomotion, possibly accompanied by anxiolytic effects, whereas the pattern of changes caused by dorsal hippocampal muscimol was consistent with anxiogenic effects. In contrast, dorsal and ventral hippocampal muscimol caused similar effects in the fear conditioning experiments, disrupting contextual, but not tone, fear conditioning. PMID- 24211450 TI - Heightened serotonin influences contest outcome and enhances expression of high intensity aggressive behaviors. AB - The outcome of behavioral interactions between organisms can have significant fitness implications. Therefore, it is of great theoretical and practical importance to understand the mechanisms that modify different agonistic behaviors. Changes in central monoamines, such as serotonin (5-HT), contribute to modifying the expression of aggressive encounters in both vertebrates and invertebrates. In several invertebrate groups, neural 5-HT has been linked to heightened aggression and conflict escalation. The male stalk-eyed fly (Teleopsis dalmanni) competes with conspecifics daily over access to resources such as food and mates. Because encounters escalate in a stereotypical manner, stalk-eyed flies provide an excellent model system to study behavioral syndromes. We hypothesized that noninvasive, pharmacological augmentation of brain 5-HT by administration of the precursor, 5-hydroxytryptophan (5-HTP), would increase stereotypic behavioral escalation and the probability of winning a conflict over food. Size-matched male 5-HTP-treated and untreated flies were placed in a forced fight paradigm and their aggressive behaviors scored. Individuals with higher brain 5-HT levels had a markedly higher probability of winning the contests, displayed greater levels of high-intensity aggressive behaviors and fewer retreats. Pretreatment with 5-HTP did not significantly alter octopamine or tyramine, suggesting that central 5-HT may modulate aggression in these organisms and play a role in determining reproductive success and resource attainment. PMID- 24211451 TI - Temporal and spectral differences in the ultrasonic vocalizations of fragile X knock out mice during postnatal development. AB - The fmr1 knock out (KO) mouse has been a useful animal model to understand pathology and treatment of FXS, both anatomically and behaviorally. Ultrasonic vocalizations (USVs) are a behavioral tool to assess early life communication deficits in mice. Here, we report on the temporal and spectral features of USVs emitted after maternal separation in wild type (FVB/N) and fmr1 KO pups at postnatal days (P) P4, P7 and P10. The results show changes in the number and duration of calls in fmr1 KO pups and wild type pups were dependent on age and call type. Fmr1 KO pups showed an increased number of USVs at P7 but not at P4 or P10. This increase was specific to Frequency Jump calls. In addition, fmr1 KO mice showed a developmental shift in the temporal distribution of calls, with P10 mice calling in distinct bout patterns. Overall, these findings provide evidence that changes in USV outcomes were specific to certain call types and ages in fmr1 KO mice. Because early postnatal life is a window during which multiple neural systems activate and become established, behavioral measures such as using USVs as a measure of communication, may be useful as a predictor of brain changes and later developmental behavioral changes. Work is needed to better understand the functional outcomes of altered development of USVs and how these changes contribute to later emergence of autistic-like behaviors in animal models of autism. PMID- 24211453 TI - Direct electrochemistry of myoglobin at reduced graphene oxide-multiwalled carbon nanotubes-platinum nanoparticles nanocomposite and biosensing towards hydrogen peroxide and nitrite. AB - We described the preparation of a novel nanobiocomposite, reduced graphene oxide- multiwalled carbon nanotubes-platinum nanoparticles/myoglobin (RGO-MWCNT-Pt/Mb) for the direct electrochemistry of myoglobin and its application towards determination of hydrogen peroxide (H2O2) and nitrite (NO2(-)). RGO-MWCNT-Pt nanocomposite has been prepared by simple solution based approach and its structure was characterized. RGO-MWCNT-Pt/Mb nanobiocomposite was prepared and attained the direct electrochemistry of Mb with pair of well-defined redox peaks with the formal potential of -0.33 V and peak to peak separation of 22 mV. Amount of electroactive protein (G) and heterogeneous electron transfer rate constant (ks) were calculated to be 1.04 * 10 (-9) mol cm(-2) and 9.47 s(-1). The sensor displayed lowest detection limit (LOD) of 6 pM which is the lowest LOD ever achieved for the detection of H2O2. Two linear ranges were observed for the detection of H2O2: (1) 10 pM-0.19 nM with sensitivity of 1.99 (+/- 0.058) uA pM( 1)cm(-2) and (2) 0.25 nM-2.24 uM with sensitivity of 0.037 (+/- 0.081) uA nM( 1)cm(-2). In addition, the biosensor offered good analytical parameters towards determination of NO2(-) with wide linear range of 1 uM to 12 mM and high sensitivity of 0.1651 (+/- 0.026) uA uM(-1) cm(-2). The sensor acquires good selectivity, repeatability, reproducibility and stability. The practical feasibility of the sensor has been addressed. PMID- 24211454 TI - Electrocatalysis and electroanalysis of nickel, its oxides, hydroxides and oxyhydroxides toward small molecules. AB - The electrocatalysis toward small molecules, especially small organic compounds, is of importance in a variety of areas. Nickel based materials such as nickel, its oxides, hydroxides as well as oxyhydroxides exhibit excellent electrocatalysis performances toward many small molecules, which are widely used for fuel cells, energy storage, organic synthesis, wastewater treatment, and electrochemical sensors for pharmaceutical, medical, food or environmental analysis. Their electrocatalytic mechanisms are proposed from three aspects such as Ni(OH)2/NiOOH mediated electrolysis, direct electrocatalysis of Ni(OH)2 or NiOOH. Under exposure to air or aqueous solution, two distinct layers form on the Ni surface with a Ni hydroxide layer at the air-oxide interface and an oxide layer between the metal substrate and the outer hydroxide layer. The transformation from nickel or its oxides to hydroxides or oxyhydroxides could be further speeded up in the strong alkaline solution under the cyclic scanning at relatively high positive potential. The redox transition between Ni(OH)2 and NiOOH is also contributed to the electrocatalytic oxidation of Ni and its oxides toward small molecules in alkaline media. In addition, nickel based materials or nanomaterials, their preparations and applications are also overviewed here. PMID- 24211452 TI - Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons. AB - Alterations of inhibitory GABAergic neurons are implicated in multiple psychiatric and neurological disorders, including schizophrenia, autism and epilepsy. In particular, interneuron deficits in prefrontal areas, along with presumed decreased inhibition, have been reported in several human patients. The majority of forebrain GABAergic interneurons arise from a single subcortical source before migrating to their final regional destination. Factors that govern the interneuron populations have been identified, demonstrating that a single gene mutation may globally affect forebrain structures or a single area. In particular, mice lacking the urokinase plasminogen activator receptor (Plaur) gene have decreased GABAergic interneurons in frontal and parietal, but not caudal, cortical regions. Plaur assists in the activation of hepatocyte growth factor/scatter factor (HGF/SF), and several of the interneuron deficits are correlated with decreased levels of HGF/SF. In some cortical regions, the interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In this study, we demonstrate decreased parvalbumin-expressing interneurons in the medial frontal cortex, but not in the hippocampus or basal lateral amygdala in the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal cortical function in extinction of cued fear conditioning and the inability to form attentional sets. Endogenous HGF/SF overexpression increased the number of PV-expressing cells in medial frontal cortical areas to levels greater than found in wildtype mice, but did not remediate the behavioral deficits. These data suggest that proper medial frontal cortical function is dependent upon optimum levels of inhibition and that a deficit or excess of interneuron numbers impairs normal cognition. PMID- 24211455 TI - Covalent fabrication of methyl parathion hydrolase on gold nanoparticles modified carbon substrates for designing a methyl parathion biosensor. AB - A biosensor based on AuNP modified GC electrodes has been developed for direct detection of methyl parathion. AuNP can be introduced to mixed monolayers of aryldiazonium salt modified GC electrodes by Au-C bonding through aryldiazonium salt chemistry, which provides a stable interface showing efficient electron transfer between biomolecules and electrodes. PEG molecules were introduced to the interface to resist non-specific protein adsorption. AuNP surfaces were further modified with 4-carboxyphenyl followed by covalent immobilization of methyl parathion hydrolase (MPH), a specific biocatalytic enzyme to methyl parathion. Exposure of this interface to methyl parathion resulted in a change in amperometric signal due to the MPH catalytic hydrolysis of methyl parathion producing electroactive compound 4-nitrophenol. This biosensor shows high selectivity, specificity, reproducibility and stability, and is functional for the detection of methyl parathion in real samples. The linear range for detection of methyl parathion is 0.2-100 ppb with a detection limit of 0.07 ppb in 0.1M phosphate buffer at pH 7.0. PMID- 24211456 TI - Electrochemical determination of cefotaxime based on a three-dimensional molecularly imprinted film sensor. AB - A novel electrochemical sensor is presented for the determination of cefotaxime (CEF), which is constructed by molecularly imprinted polymer (MIP), gold networks@IL (IL, 1-butyl-3-methylimidazolium tetrafluoroborate, [BMIM][BF4]) (GNWs@IL), porous platinum nanoparticles (PPNPs) and carboxyl graphene (COOH-r GO). The GNWs@IL is prepared by directly reducing HAuCl4 with sodium citrate in [BMIM][BF4] aqueous solution. The PPNPs are well embedded in GNWs@IL due to the adhesion of IL to form GNWs@IL-PPNPs suspension, which is coated on a COOH-r-GO modified glassy carbon electrode to construct a porous three-dimensional networks modified electrode. Then, MIP is prepared by cyclic voltammetry at the modified electrode, using CEF as template and o-phenylenediamine as monomer. The factors concerning this assay strategy are carefully investigated. Under the optimal conditions, the electrochemical sensor offers an excellent response for CEF, the linear response range is 3.9 * 10(-9) ~ 8.9 * 10(-6) mol L(-1) and the detection limit is 1.0 * 10(-10) mol L(-1). The electrochemical sensor has been applied to the determination of CEF in real samples with satisfactory results. PMID- 24211458 TI - Sandwich-format electrochemiluminescence assays for tumor marker based on PAMAM dendrimer-L-cysteine-hollow gold nanosphere nanocomposites. AB - In this work, a novel polyamidoamine (PAMAM) dendrimer-L-cysteine-hollow gold nanospheres nanocomposite was fabricated and used as the promoter for the peroxydisulfate/O2 ECL system to detect the concentration of the tumor marker carcinoembryonic antigen (CEA). Herein, the carboxyl-terminated PAMAM dendrimers were decorated with L-cysteine (L-Cys) by EDC/NHS coupling chemistry. Then, the hollow gold nanospheres (HGNPs) were employed as effective nano-carriers for the assembly of PAMAM-L-Cys via thiols-Au bonding, which was used for further loading of detection antibody (Ab2) to form the PAMAM-L-Cys-HGNPs-Ab2 bioconjugates. In the presence of target CEA, the sandwiched immuno-structure can be formed between the capture anti-CEA antibodies (Ab1), which self-assembled on deposited gold modified electrode, and the Ab2 on the PAMAM-L-Cys-HGNPs, thereby resulting in a proportional increase in ECL response, due to the significant enhancement of PAMAM-L-Cys-HGNPs toward peroxydisulfate/O2 ECL system. As a result, a sandwich ECL assay for CEA detection was developed with excellent sensitivity of a large concentration variation from 20 fg/mL to 1.0 ng/mL and a detection limit of 6.7 fg mL(-1). PMID- 24211457 TI - Nanopore detection of copper ions using a polyhistidine probe. AB - We report a stochastic nanopore sensing method for the detection of Cu(2+) ions. By employing a polyhistidine molecule as a chelating agent, and based on the different signatures of the events produced by the translocation of the chelating agent through an alpha-hemolysin pore in the absence and presence of target analytes, trace amounts of copper ions could be detected with a detection limit of 40 nM. Importantly, although Co(2+), Ni(2+), and Zn(2+) also interacts with the polyhistidine molecule, since the event residence times and/or blockage amplitudes for these metal chelates are significantly different from those of copper chelates, these metal ions do not interfere with Cu(2+) detection. This chelating reaction approach should find useful application in the development of nanopore sensors for other metal ions. PMID- 24211459 TI - Competitive-type displacement reaction for direct potentiometric detection of low abundance protein. AB - Prostate-specific antigen (PSA), one of the indications of possible prostate malignancy, is used as a biomarker for the diagnosis and prognosis of prostate cancer. Herein, we develop a new homogeneous potentiometric immunoassay for sensitive detection of low-concentration PSA without the need of sample separation and washing step. Two nanostructures including positively charged polyethyleneimine-poly(styrene-co-acrylic acid) (PEI-PSAA) nanospheres and negatively charged gold nanoparticles conjugated with anti-PSA antibody (Ab-AuNP) were first synthesized by using mulsifier-free emulsion copolymerization and wet chemistry method, respectively. Thereafter, the as-prepared PEI-PSAA was used as a pseudo hapten for the construction of immunosensing probe based on an electrostatic interaction between PEI-PSAA and Ab-AuNP. Upon target introduction, the added PSA competed with PEI-PASS for Ab-AuNP based on a specific antigen antibody interaction, and displaced Ab-AuNP from PEI-PASS. The dissociated PEI PASS was captured through the negatively charged Nafion- modified electrode, thereby resulting in the change of membrane potential. The fabrication process was characterized by using high-resolution transmission electron microscope (HRTEM), scanning electron microscope with energy-dispersive X-ray spectroscopy (SEM-EDX), surface plasmon resonance (SPR) and dynamic laser scattering (DLS) technique. Under optimal conditions, the output signal was indirectly proportional to the concentration of target PSA in the sample and exhibited a dynamic range from 0.1 to 50 ng/mL with a detection limit (LOD) of 0.04 ng/mL. Intra- and inter-assay coefficients of variation (CVs) were 6.8 and 7.5%, respectively. In addition, the methodology was evaluated for analysis of 12 clinical serum samples and showed good accordance between the results obtained by the developed immunosensing protocol and a commercialized enzyme-linked immunosorbent assay (ELISA) method. PMID- 24211460 TI - Amperometric cholesterol biosensor based on the direct electrochemistry of cholesterol oxidase and catalase on a graphene/ionic liquid-modified glassy carbon electrode. AB - Cholesterol oxidase (ChOx) and catalase (CAT) were co-immobilized on a graphene/ionic liquid-modified glassy carbon electrode (GR-IL/GCE) to develop a highly sensitive amperometric cholesterol biosensor. The H2O2 generated during the enzymatic reaction of ChOx with cholesterol could be reduced electrocatalytically by immobilized CAT to obtain a sensitive amperometric response to cholesterol. The direct electron transfer between enzymes and electrode surface was investigated by cyclic voltammetry. Both enzymes showed well-defined redox peaks with quasi-reversible behaviors. An excellent sensitivity of 4.163 mA mM(-1)cm(-2), a response time less than 6s, and a linear range of 0.25-215 MUM (R(2)>0.99) have been observed for cholesterol determination using the proposed biosensor. The apparent Michaelis-Menten constant (KM(app)) was calculated to be 2.32 mM. The bienzymatic cholesterol biosensor showed good reproducibility (RSDs<5%) with minimal interference from the coexisting electroactive compounds such as ascorbic acid and uric acid. The CAT/ChOx/GR-IL/GCE showed excellent analytical performance for the determination of free cholesterol in human serum samples. PMID- 24211461 TI - The unfolding of G-quadruplexes and its adverse effect on DNA-gold nanoparticles based sensing system. AB - The adsorption of DNAs in G-quadruplex solution onto 13 nm gold nanoparticles (AuNPs) was studied through monitoring of the localized surface plasmon resonance (LSPR) absorbance of 13 nm AuNPs at 520 and 650 nm (A650/A520) in the solutions of three widely studied guanine-rich sequences, TBA(5'-GGTTGGTGTGGTTGG-3'), PW17(5'-GGGTAGGGCGGGTTGGG-3'), and PSO (5'-GGGTTAGGGTTAGGGTTAGGG-3'). It was found that the degree of adsorption of DNAs in Pb(2+) stabilized G-quadruplex (G Pb(2+)) solutions is up to 93% after more than 5h of incubation. Furthermore, the lead concentrations in the solutions containing G-quadruplex and AuNP were analyzed by an inductively coupled plasma atomic emission spectrometer. The results showed that Pb(2+) had been released from the G-quadruplexes, which means the G-quadruplexes may be unfolded in the presence of AuNP. This interaction between G-quadruplexes and AuNP demonstrated that long time incubation between DNAs and AuNPs would possibly make it unable to distinguish G-quadruplex from ssDNA. Thus, a biosensing system consisting of PW17 and AuNPs was developed to detect Pb(2+). It was found that the LSPR responses at A650/A520 were sensitive to [Pb(2+)]. However, the sensitivity of the system was interfered by the potential unfolding of PW17-Pb(2+) in the presence of AuNPs. This unexpected adverse effect of AuNPs on DNA-based biosensors should be taken into consideration in the future development of biosensing systems that are based on ssDNA aptamers and unmodified AuNPs. PMID- 24211462 TI - A size selective porous silicon grating-coupled Bloch surface and sub-surface wave biosensor. AB - A porous silicon (PSi) grating-coupled Bloch surface and sub-surface wave (BSW/BSSW) biosensor is demonstrated to size selectively detect the presence of both large and small molecules. The BSW is used to sense large immobilized analytes at the surface of the structure while the BSSW that is confined inside but near the top of the structure is used to sensitively detect small molecules. Functionality of the BSW and BSSW modes is theoretically described by dispersion relations, field confinements, and simulated refractive index shifts within the structure. The theoretical results are experimentally verified by detecting two different small chemical molecules and one large 40 base DNA oligonucleotide. The PSi-BSW/BSSW structure is benchmarked against current porous silicon technology and is shown to have a 6-fold higher sensitivity in detecting large molecules and a 33% improvement in detecting small molecules. This is the first report of a grating-coupled BSW biosensor and the first report of a BSSW propagating mode. PMID- 24211463 TI - Naked eye detection of trace cancer biomarkers based on biobarcode and enzyme assisted DNA recycling hybrid amplifications. AB - Naked eye-based detection has received increasing research interest due to the simplicity nature of this type of assay. However, improving the sensitivity of the naked eye detection method for the monitoring of trace amount of target molecules remains a major challenge. Herein, we describe a biobarcode and an enzyme-assisted DNA recycling hybrid amplification strategy for naked eye detection of sub-picomolar carcinoembryonic antigen (CEA), a cancer biomarker. The presence of CEA and the corresponding antibodies results in the formation of immunocomplexes and the capture of the biobarcodes in a microplate. The massive barcode DNAs released from the biobarcodes hybridize with the G-quadruplex inactive hairpin DNA probes and form catalytic nicking sites for N.BstNBI endonuclease, which cleaves the barcode DNA/hairpin partial dsDNA, releases the G quadruplex active sequences and recycles the barcode DNA. Due to the barcode DNA recycling process, numerous G-quadruplex active sequences are generated and associate with hemin to form peroxidase mimicking enzymes, which convert colorless ABTS(2-) to green color intensified ABTS(*-) to achieve naked eye detection of CEA down to 0.025 ng mL(-1) (0.14 pM). The naked eye detection strategy reported herein can be applied also to complicated serum sample matrix, making this approach hold great promise for point-of-care diagnostic applications. PMID- 24211464 TI - The heritability of volumes of brain structures and its relationship to age: a review of twin and family studies. AB - Total brain volume (BV) and the volumes of brain substructures are influenced by genes, the magnitude of which changes with age. One approach to the examination of genetic influences on the volumes of brain structures is to determine their heritability using twin and family studies. We reviewed published cross-sectional studies which examined heritability in healthy subjects at different ages. We identified 32 studies, which examined a total of 77 brain volumetric measures. The findings of our review showed that BVs are under significant genetic influence at all ages, although different brain regions showed different heritability levels. Furthermore, the cross-sectional approach of our review found that heritability factor for the majority of BVs declined with age, such as in the total brain and cerebrum, followed by subsequent increment of environmental influences. Overall, this study identified for the first time a cross-sectional pattern for brain structures' heritability changes with age, and suggests the potential for longitudinal investigations in the future. PMID- 24211465 TI - Molecular dynamics simulations studies and free energy analysis on inhibitors of MDM2-p53 interaction. AB - The oncoprotein MDM2 (murine double minute 2) negatively regulates the activity and stability of tumor suppressor p53. Inactivation of the MDM2-p53 interaction by potent inhibitors offers new possibilities for anticancer therapy. Molecular dynamics (MD) simulations were performed on three inhibitors-MDM2 complexes to investigate the stability and structural transitions. Simulations show that the backbone of MDM2 maintains stable during the whole time. However, slightly structural changes of inhibitors and MDM2 are observed. Furthermore, the molecular mechanics generalized Born surface area (MM-GBSA) approach was introduced to analyze the interactions between inhibitors and MDM2. The results show that binding of inhibitor pDIQ to MDM2 is significantly stronger than that of pMI and pDI to MDM2. The side chains of residues have more contribution than backbone of residues in energy decomposition. The structure-affinity analyses show that L54, I61, M62, Y67, Q72, H73 and V93 produce important interaction energy with inhibitors. The residue W/Y22' is also very important to the interaction between the inhibitors and MDM2. The three-dimensional structures at different times indicate that the mobility of Y100 influences on the binding of inhibitors to MDM2, and its change has important role in conformations of inhibitors and MDM2. PMID- 24211466 TI - Network visualization of conformational sampling during molecular dynamics simulation. AB - Effective data reduction methods are necessary for uncovering the inherent conformational relationships present in large molecular dynamics (MD) trajectories. Clustering algorithms provide a means to interpret the conformational sampling of molecules during simulation by grouping trajectory snapshots into a few subgroups, or clusters, but the relationships between the individual clusters may not be readily understood. Here we show that network analysis can be used to visualize the dominant conformational states explored during simulation as well as the connectivity between them, providing a more coherent description of conformational space than traditional clustering techniques alone. We compare the results of network visualization against 11 clustering algorithms and principal component conformer plots. Several MD simulations of proteins undergoing different conformational changes demonstrate the effectiveness of networks in reaching functional conclusions. PMID- 24211467 TI - Visualizing side chains of invisible protein conformers by solution NMR. AB - Sparsely populated and transiently formed protein conformers can play key roles in many biochemical processes. Understanding the structure function paradigm requires, therefore, an atomic-resolution description of these rare states. However, they are difficult to study because they cannot be observed using standard biophysical techniques. In the past decade, NMR methods have been developed for structural studies of these elusive conformers, focusing primarily on backbone (1)H, (15)N and (13)C nuclei. Here we extend the methodology to include side chains by developing a (13)C-based chemical exchange saturation transfer experiment for the assignment of side-chain aliphatic (13)C chemical shifts in uniformly (13)C labeled proteins. A pair of applications is provided, involving the folding of beta-sheet Fyn SH3 and alpha-helical FF domains. Over 96% and 89% of the side-chain (13)C chemical shifts for excited states corresponding to the unfolded conformation of the Fyn SH3 domain and a folding intermediate of the FF domain, respectively, have been obtained, providing insight into side-chain packing and dynamics. PMID- 24211468 TI - Protein-mediated chromosome pairing of repetitive arrays. AB - Chromosomally integrated arrays of lacO and tetO operator sites visualized by LacI and TetR repressor proteins fused with GFP (green fluorescent protein) (or other fluorescent proteins) are widely used to monitor the behavior of chromosomal loci in various systems. However, insertion of such arrays and expression of the corresponding proteins is known to perturb genomic architecture. In several cases, juxtaposition of such arrays located on different chromosomes has been inferred to reflect pairing of the corresponding loci. Here, we report that a version of TetR-GFP mutated to disrupt GFP dimerization (TetR A206KGFP or "TetR-kGFP") abolishes pairing of tetO arrays in vivo and brings spatial proximity of chromosomal loci marked with those arrays back to the wild type level. These data argue that pairing of arrays is caused by GFP dimerization and thus presents an example of protein-assisted interaction in chromosomes. Arrays marked with another protein, TetR-tdTomato, which has a propensity to form intramolecular dimers instead of intermolecular dimers, also display reduced level of pairing, supporting this idea. TetR-kGFP provides an improved system for studying chromosomal loci with a low pairing background. PMID- 24211470 TI - Public health program planning logic model for community engaged type 2 diabetes management and prevention. AB - Diabetes remains a growing epidemic with widening health inequity gaps in disease management, self-management knowledge, access to care and outcomes. Yet there is a paucity of evaluation tools for community engaged interventions aimed at closing the gaps and improving health. The Guide to Community Preventive Services (the Community Guide) developed by the Task Force on Community Preventive Services (the Task Force) at the Centers for Disease Control and Prevention (CDC) recommends two healthcare system level interventions, case management interventions and disease management programs, to improve glycemic control. However, as a public health resource guide for diabetes interventions a model for community engagement is a glaringly absent component of the Community Guide recommendations. In large part there are few evidence-based interventions featuring community engagement as a practice and system-level focus of chronic disease and Type 2 diabetes management. The central argument presented in this paper is that the absence of these types of interventions is due to the lack of tools for modeling and evaluating such interventions, especially among disparate and poor populations. A conceptual model emphasizing action-oriented micro-level community engagement is needed to complement the Community Guide and serve as the basis for testing and evaluation of these kinds of interventions. A unique logic model advancing the Community Guide diabetes recommendations toward measureable and sustainable community engagement for improved Type 2 diabetes outcomes is presented. PMID- 24211469 TI - Structural complementation of the catalytic domain of pseudomonas exotoxin A. AB - The catalytic moiety of Pseudomonas exotoxin A (domain III or PE3) inhibits protein synthesis by ADP-ribosylation of eukaryotic elongation factor 2. PE3 is widely used as a cytocidal payload in receptor-targeted protein toxin conjugates. We have designed and characterized catalytically inactive fragments of PE3 that are capable of structural complementation. We dissected PE3 at an extended loop and fused each fragment to one subunit of a heterospecific coiled coil. In vitro ADP-ribosylation and protein translation assays demonstrate that the resulting fusions-supplied exogenously as genetic elements or purified protein fragments had no significant catalytic activity or effect on protein synthesis individually but, in combination, catalyzed the ADP-ribosylation of eukaryotic elongation factor 2 and inhibited protein synthesis. Although complementing PE3 fragments are catalytically less efficient than intact PE3 in cell-free systems, co expression in live cells transfected with transgenes encoding the toxin fusions inhibits protein synthesis and causes cell death comparably as intact PE3. Complementation of split PE3 offers a direct extension of the immunotoxin approach to generate bispecific agents that may be useful to target complex phenotypes. PMID- 24211471 TI - Biomimetic self-assembly of apatite hybrid materials: from a single molecular template to bi-/multi-molecular templates. AB - The self-assembly of apatite and proteins is a critical process to induce the formation of the bones and teeth in vertebrates. Although hierarchical structures and biomineralization mechanisms of the mineralized tissues have been intensively studied, most researches focus on the self-assembly biomimetic route using one single-molecular template, while the natural bone is an outcome of a multi molecular template co-assembly process. Inspired by such a mechanism in nature, a novel strategy based on multi-molecular template co-assembly for fabricating bone like hybrid materials was firstly proposed by the authors. In this review article we have summarized the new trends from single-molecular template to bi-/multi molecular template systems in biomimetic fabrication of apatite hybrid materials. So far, many novel apatite hybrid materials with controlled morphologies and hierarchical structures have been successfully achieved using bi-/multi-molecular template strategy, and are found to have multiple common features in comparison with natural mineralized tissues. The carboxyl, carbonyl and amino groups of the template molecules are identified to initiate the nucleation of calcium phosphate during the assembling process. For bi-/multi-molecular templates, the incorporation of multiple promotion sites for calcium and phosphate ions precisely enables to regulate the apatite nucleation from the early stage. The roles of acidic molecules and the synergetic effects of protein templates have been significantly recognized in recent studies. In addition, a specific attention is paid to self-assembling of apatite nanoparticles into ordered structures on tissue regenerative scaffolds due to their promising clinical applications ranging from implant grafts, coatings to drug and gene delivery. PMID- 24211472 TI - The history of tomato: from domestication to biopharming. AB - Imported from the Andean region to Europe in the 16th century, today tomato is widespread throughout the world and represents the most economically important vegetable crop worldwide. Tomato is not only traded in the fresh market but is also used in the processing industry in soups, as paste, concentrate, juice, and ketchup. It is an incredible source of important nutrients such as lycopene, beta carotene and vitamin C, which all have positive impacts on human health. Its production and consumption is increasing with population growth. In this review, we report how tomato was already domesticated by the ancient Incan and Aztec civilizations, and how it came to Europe, where its breeding history started. The development of genetic, molecular biology and plant biotechnology have opened the doors towards the modern genetic engineering of tomato. The different goals of tomato genetic engineering are presented, as well as examples of successfully engineered tomatoes in terms of resistance to biotic and abiotic stresses, and fruit quality. The development of GM tomato for biopharming is also described. PMID- 24211473 TI - Biomaterials surfaces capable of resisting fungal attachment and biofilm formation. AB - Microbial attachment onto biomedical devices and implants leads to biofilm formation and infection; such biofilms can be bacterial, fungal, or mixed. In the past 15 years, there has been an increasing research effort into antimicrobial surfaces but the great majority of these publications present research on bacteria, with some reports also testing resistance to fungi. Very few studies have focused exclusively on antifungal surfaces. However, with increasing recognition of the importance of fungal infections to human health, particularly related to infections at biomaterials, it would seem that the interest in antifungal surfaces is disproportionately low. In studies of both bacteria and fungi, fungi tend to be the minor focus with hypothesized antibacterial mechanisms of action often generalized to also explain the antifungal effect. Yet bacteria and fungi represent two Distinct biological Domains and possess substantially different cellular physiology and structure. Thus it is questionable whether these generalizations are valid. Here we review the scientific literature focusing on surface coatings prepared with antifungal agents covalently attached to the biomaterial surface. We present a critical analysis of generalizations and their evidence. This review should be of interest to researchers of "antimicrobial" surfaces by addressing specific issues that are key to designing and understanding antifungal biomaterials surfaces and their putative mechanisms of action. PMID- 24211474 TI - Engineering proteins for thermostability through rigidifying flexible sites. AB - Engineering proteins for thermostability is an exciting and challenging field since it is critical for broadening the industrial use of recombinant proteins. Thermostability of proteins arises from the simultaneous effect of several forces such as hydrophobic interactions, disulfide bonds, salt bridges and hydrogen bonds. All of these interactions lead to decreased flexibility of polypeptide chain. Structural studies of mesophilic and thermophilic proteins showed that the latter need more rigid structures to compensate for increased thermal fluctuations. Hence flexibility can be an indicator to pinpoint weak spots for enhancing thermostability of enzymes. A strategy has been proven effective in enhancing proteins' thermostability with two steps: predict flexible sites of proteins firstly and then rigidify these sites. We refer to this approach as rigidify flexible sites (RFS) and give an overview of such a method through summarizing the methods to predict flexibility of a protein, the methods to rigidify residues with high flexibility and successful cases regarding enhancing thermostability of proteins using RFS. PMID- 24211475 TI - Nanotechnology-based intelligent drug design for cancer metastasis treatment. AB - Traditional chemotherapy used today at clinics is mainly inherited from the thinking and designs made four decades ago when the Cancer War was declared. The potency of those chemotherapy drugs on in-vitro cancer cells is clearly demonstrated at even nanomolar levels. However, due to their non-specific effects in the body on normal tissues, these drugs cause toxicity, deteriorate patient's life quality, weaken the host immunosurveillance system, and result in an irreversible damage to human's own recovery power. Owing to their unique physical and biological properties, nanotechnology-based chemotherapies seem to have an ability to specifically and safely reach tumor foci with enhanced efficacy and low toxicity. Herein, we comprehensively examine the current nanotechnology-based pharmaceutical platforms and strategies for intelligent design of new nanomedicines based on targeted drug delivery system (TDDS) for cancer metastasis treatment, analyze the pros and cons of nanomedicines versus traditional chemotherapy, and evaluate the importance that nanomaterials can bring in to significantly improve cancer metastasis treatment. PMID- 24211476 TI - Lack of herd immunity against measles in individuals aged <35 years could explain re-emergence of measles in Catalonia (Spain). AB - OBJECTIVES: The objective of this study was to assess the association between lack of herd immunity in some population groups and the re-emergence of measles in Catalonia in 2006. METHODS: Herd immunity was considered established in the different population groups when the prevalence of positive serological results to measles was higher than the herd immunity threshold of 90%. The Chi-square test and the odds ratio were used to assess the association between lack of herd immunity and measles cases in the outbreak of 2006-2007. RESULTS: Herd immunity was not established against measles in individuals aged 0-14 years and 25-34 years, as the prevalence of positive serological results was <90% in these groups. In the measles outbreak of 2006-2007, 91% of cases occurred in age groups without herd immunity, and only 9% of cases occurred in age groups with herd immunity (p<0.001). The odds ratio for the association between lack of herd immunity and measles cases in the outbreak of 2006-2007 was 104 (p<0.001). CONCLUSION: Lack of herd immunity in individuals aged<35 years could be one of the factors underlying the re-emergence of measles in Catalonia. PMID- 24211477 TI - Three decades of MSM donor deferral policies. What have we learned? AB - In the early 1980s, donor deferrals targeting men who have sex with men (MSM) and other high-risk groups were implemented in response to the outbreak of HIV/AIDS. It has now been three decades since the implementation of these deferrals. We review the international experience with developing these policies, which involves combining scientific evidence with ethical and moral concerns and the challenge of moving from precautionary to risk management policies as scientific knowledge and technology evolves. We provide key lessons that can guide blood policymakers as they confront potential new threats to the safety of the blood system and also provide lessons to the wider public health community on how best to incorporate precaution into the policymaking process. PMID- 24211478 TI - Risk factors for new-onset late postpartum preeclampsia in women without a history of preeclampsia. AB - OBJECTIVE: Risk factors for the development of new-onset late postpartum preeclampsia (LPP) in women without any history of preeclampsia are not known. Because identification of women who are at risk may lead to an earlier diagnosis of disease and improved maternal outcomes, this study identified risk factors (associated patient characteristics) for new-onset LPP. STUDY DESIGN: A case control study of 34 women with new-onset LPP and 68 women without new-onset LPP after normal delivery, who were matched on date of delivery, was conducted at Mount Sinai Hospital, New York, NY. Data were collected by chart review. Exact conditional logistic regression identified patient characteristics that were associated with new-onset LPP. RESULTS: New-onset LPP was associated with age >=40 years (adjusted odds ratio, 24.83; 95% confidence interval [CI], 1.43 infinity; P = .03), black race (adjusted odds ratio, 78.35; 95% CI, 7.25 infinity; P < .001), Latino ethnicity (adjusted odds ratio, 19.08; 95% CI, 2.73 infinity; P = .001), final pregnancy body mass index of >=30 kg/m(2) (adjusted odds ratio, 13.38; 95% CI, 1.87-infinity; P = .01), and gestational diabetes mellitus (adjusted odds ratio, 72.91; 95% CI, 5.52-infinity; P < .001). As predictive tests for new-onset LPP, the sensitivity and specificity of having >=1 of these characteristics was 100% and 59%, respectively, and the sensitivity and specificity of having >=2 was 56% and 93%, respectively. CONCLUSION: Older age, black race, Latino ethnicity, obesity, and a pregnancy complicated by gestational diabetes mellitus all are associated positively with the development of new-onset LPP. Closer observation may be warranted in these populations. PMID- 24211479 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent high-grade uterine sarcoma with peritoneal dissemination. AB - OBJECTIVE: Peritoneal sarcomatosis from primary uterine sarcoma (US) is a rare condition. Conventional therapeutic modalities have failed to improve survival and outcomes among patients with high-grade US with extrapelvic spread. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown improved outcomes for peritoneal carcinomatosis from other epithelial primaries with similar clinical presentation. We report our experience applying this treatment in 3 patients with recurrent high-grade US with peritoneal dissemination. STUDY DESIGN: This retrospective review of a prospective database of 378 patients with peritoneal dissemination of cancer treated with CRS/HIPEC identified 3 patients with recurrent high-grade US. Follow up for disease progression was carried out by physical examination and computed tomography scan of the chest, abdomen, and pelvis. RESULTS: Two leiomyosarcomas and 1 adenosarcoma with sarcomatous overgrowth were identified. Two of the 3 had failed standard treatment with surgery and systemic chemotherapy before CRS/HIPEC was performed. Follow-up ranged from 34 to 140 months. All 3 patients are alive, 2 with no evidence of disease (NED), and 1 alive with disease. Adramycin/cisplatin was used for HIPEC in 1 case (140 months with NED), whereas melphalan was used in the other 2 cases (53 months alive with disease, 34 months with NED). Two patients underwent 1 CRS/HIPEC, whereas 1 required 3 CRS/HIPEC due to disease recurrence. CONCLUSION: CRS/HIPEC shows promise as a treatment modality for the management of selected patients with recurrent high-grade US with peritoneal dissemination. Further studies are warranted. PMID- 24211480 TI - Apgar score of 0 at 5 minutes and neonatal seizures or serious neurologic dysfunction in relation to birth setting. PMID- 24211481 TI - Reply: To PMID 23791692. PMID- 24211482 TI - Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma. AB - OBJECTIVES: This study evaluated fertility and oncological outcomes in women with complex atypical hyperplasia (CAH) or nonmyoinvasive grade 1 endometrioid endometrial carcinoma (EM) who desired fertility-sparing therapy. STUDY DESIGN: The retrospective cohort study included women younger than 45 years with CAH or EM who desired fertility-sparing treatment at our institution. Only patients for whom both oncological treatment and pregnancy outcomes were available were included. Statistical analyses were performed using a Fisher exact test, Pearson chi(2) test, and Spearman rank correlation test, as appropriate. RESULTS: Seventy five patients were identified, and 23 (13 CAH, 10 EM) met the inclusion criteria. All 23 patients had at least 1 prior pregnancy. Treatment was split between oral progesterone only (38.5% CAH, 40% EM), levonorgestrel intrauterine device only (30.8% CAH, 20% EM), and both (30.8% CAH, 40% EM). After a median follow-up of 13 months (range, 3-74 months), 9 patients (46.2% CAH, 30% EM, P = .39) had persistent/progressive disease. Eight patients (30.8% CAH, 40% EM, P = .69) ultimately had a hysterectomy, and 3 of these (13.0%) were found to have persistent/progressive disease. Median time from diagnosis to hysterectomy was 13 months (range, 4-56 months). Fourteen of the 23 patients utilized assisted reproductive techniques (60.9%); 12 underwent IVF and 2 chose a gestation carrier. Seven clinical intrauterine pregnancies (30.4%) resulting in 6 live births (26.1%) were found in the entire cohort. CONCLUSION: Fertility-sparing treatment for CAH and grade 1 endometrial cancer is feasible with progestin therapy and leads to clinically meaningful rates of pregnancy in young women who desire fertility. PMID- 24211483 TI - Large for gestational age and long-term cognitive function. AB - OBJECTIVE: As we have previously published, small-for-gestational-age (<3% birthweight [BW]) newborns exhibit catch-up cognitive functioning by age 2 years. Our objective was to compare cognitive functioning in children born with >=90% vs 5-89% BW for gestational age (WGA) between 9 months and kindergarten. STUDY DESIGN: Nonanomalous singletons from Early Childhood Longitudinal Study-Birth Cohort with BW >=90% vs 5-89% were compared. Cognitive and academic functioning was measured at 4 time points: 9 months, and 2, 3.5, and 5.5 years. Associations between WGA and cognitive functioning at each time point was examined using confounder-adjusted general linear model-based methods. RESULTS: Of 2930 cases, 271 (9.2%) were >=90% WGA. In terms of cognitive performance, children >=90% WGA were not statistically different (P = .068) from normal WGA at any time point, nor did they change at different rates across early childhood. CONCLUSION: There is no difference in cognitive function in children with BW 5-89% vs >=90% for GA. PMID- 24211484 TI - Elevated tissue omega-3 fatty acid status prevents age-related glucose intolerance in fat-1 transgenic mice. AB - The objective of this study was to investigate the impact of elevated tissue omega-3 (n-3) polyunsaturated fatty acids (PUFA) status on age-related glucose intolerance utilizing the fat-1 transgenic mouse model, which can endogenously synthesize n-3 PUFA from omega-6 (n-6) PUFA. Fat-1 and wild-type mice, maintained on the same dietary regime of a 10% corn oil diet, were tested at two different ages (2 months old and 8 months old) for various glucose homeostasis parameters and related gene expression. The older wild-type mice exhibited significantly increased levels of blood insulin, fasting blood glucose, liver triglycerides, and glucose intolerance, compared to the younger mice, indicating an age-related impairment of glucose homeostasis. In contrast, these age-related changes in glucose metabolism were largely prevented in the older fat-1 mice. Compared to the older wild-type mice, the older fat-1 mice also displayed a lower capacity for gluconeogenesis, as measured by pyruvate tolerance testing (PTT) and hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase). Furthermore, the older fat-1 mice showed a significant decrease in body weight, epididymal fat mass, inflammatory activity (NFkappa-B and p-IkappaB expression), and hepatic lipogenesis (acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) expression), as well as increased peroxisomal activity (70-kDa peroxisomal membrane protein (PMP70) and acyl-CoA oxidase1 (ACOX1) expression). Altogether, the older fat-1 mice exhibit improved glucose homeostasis in comparison to the older wild-type mice. These findings support the beneficial effects of elevated tissue n-3 fatty acid status in the prevention and treatment of age-related chronic metabolic diseases. PMID- 24211485 TI - Continuous syngas fermentation for the production of ethanol, n-propanol and n butanol. AB - Syngas fermentation to fuels is a technology on the verge of commercialization. Low cost of fermentation medium is important for process feasibility. The use of corn steep liquor (CSL) instead of yeast extract (YE) in Alkalibaculum bacchi strain CP15 bottle fermentations reduced the medium cost by 27% and produced 78% more ethanol. When continuous fermentation was performed in a 7-L fermentor, 6g/L ethanol was obtained in the YE and YE-free media. When CSL medium was used in continuous fermentation, the maximum produced concentrations of ethanol, n propanol and n-butanol were 8 g/L, 6 g/L and 1 g/L, respectively. n-Propanol and n-butanol were not typical products of strain CP15. A 16S rRNA gene-based survey revealed a mixed culture in the fermentor dominated by A. bacchi strain CP15 (56%) and Clostridium propionicum (34%). The mixed culture presents an opportunity for higher alcohols production from syngas. PMID- 24211486 TI - Characteristics of aerobic granulation at mesophilic temperatures in wastewater treatment. AB - Compact and structurally stable aerobic granules were developed in a sequencing batch reactor (SBR) at mesophilic temperatures (35 degrees C). The morphological, biological and chemical characteristics of the aerobic granulation were investigated and a theoretical granulation mechanism was proposed according to the results of the investigation. The mature aerobic granules had compact structure, small size (mean diameter of 0.24 mm), excellent settleability and diverse microbial structures, and were effective for the removal of organics and nitrification. The growth kinetics demonstrated that the biomass growth depended on coexistence and interactions between heterotrophs and autotrophs in the granules. The functions of heterotrophs and autotrophs created a compact and secure layer on the outside of the granules, protecting the inside sludge containing environmentally sensitive and slow growing microorganisms. The mechanism and the reactor performance may promise feasibility and efficiency for treating industry effluents at mesophilic temperatures using aerobic granulation. PMID- 24211487 TI - A comparative study of nitrogen conversion during pyrolysis of coconut fiber, its corresponding biochar and their blends with lignite. AB - In the present study, the conversion of fuel-N to HCN and NH3 was investigated during rapid pyrolysis of raw biomass (coconut fiber), its corresponding biochar and their blends with lignite within a temperature range of 600-900 degrees C. The results showed that the raw biomass and the biochar showed totally different nitrogen partitioning between NH3 and HCN. HCN was the dominant nitrogen pollutant from pyrolysis of raw biomass, while for the biochar pyrolysis the yield of NH3 was slightly higher than that of HCN. Synergistic interactions occurred within both raw biomass/lignite and biochar/lignite blends, especially for the biochar/lignite blend, and resulted in reduced yields of HCN and NH3, decreased the total nitrogen percentage retained in the char and promoted harmless N2 formation. These findings suggest that biochar/lignite co-firing for energy production may have the enhanced benefit of reduced emissions of nitrogen pollutants than raw biomass/lignite. PMID- 24211488 TI - Stimulatory effect of ghrelin on food intake in bullfrog larvae. AB - Ghrelin is a potent orexigenic peptide implicated in appetite regulation in rodents. However, except for teleost fish, the involvement of ghrelin in the regulation of feeding in non-mammalian vertebrates has not been well studied. Anuran amphibian larvae feed and grow during the pre- and prometamorphic stages, but, thereafter they stop feeding as the metamorphic climax approaches. Therefore, orexigenic factors seem to play important roles in growing larvae. In the present study, we examined the effect of intraperitoneal (IP) or intracerebroventricular (ICV) administration of synthetic bullfrog ghrelin (n octanoylated 28-amino acid form) on food intake in larvae at the prometamorphic stages. Cumulative food intake was significantly increased by IP (8 and 16pmol/g body weight (BW)) or ICV (0.5 and 1pmol/g BW) administration of ghrelin during a 15-min observation period. The orexigenic action of ghrelin at 8pmol/g BW (IP) or at 0.5pmol/g BW (ICV) was blocked by treatment with a growth hormone secretagogue receptor antagonist, [D-Lys(3)]GHRP-6 at 80pmol/g BW (IP) or at 5pmol/g BW (ICV). We then investigated the effect of feeding status on expression levels of the ghrelin transcript in the hypothalamus and gastrointestinal tract. Ghrelin mRNA levels in both were decreased 15 and 60min after feeding. These results indicate that ghrelin acts as an orexigenic factor in bullfrog larvae. PMID- 24211489 TI - Efficacy and side effects of albendazole currently in use against Ascaris, Trichuris and hookworm among school children in Wondo Genet, southern Ethiopia. AB - Monitoring the efficacy of anthelminthic drugs is essential. The objective of this study was to assess the efficacy of a single oral dose of 400mg albendazole (ABZ) against the major soil-transmitted helminth (STH) infection in school children, Wondo Genet, southern Ethiopia. A single fresh stool sample was collected from 298 school children and examined using a duplicate smear of the Kato-Katz method. Children positive for STH infections were treated with single oral dose of 400mg ABZ and re-examined for intestinal helminth infections 21days post-treatment. The participants were interviewed for symptoms related with the drug uptake 24h after ABZ treatment. Children positive for Schistosoma mansoni infections were treated with Praziquantel (40mg/kg of body weight) after an ABZ treatment follow up survey. 51.3%, 49.7%, 44.6% and 88.3% had hookworm, Ascaris lumbricoides, Trichuris trichiura and any intestinal helminth infection, respectively. Cure rates were 97.4% for hookworm, 96.6% for A. lumbricoides and 30.8% for T. trichiura infections. Egg reduction rates (ERRs) were 99.8% for hookworm, 99.9% for A. lumbricoides and 83.1% for T. trichiura infections. Mild and transient symptoms were observed among the participants which were quite frequent. In conclusion, a 400mg single oral dose of ABZ was effective against hookworm and A. lumbricoides but less efficacious against T. trichiura infection. The drug resulted in high ERRs for hookworm, A. lumbricoides and T. trichiura. Administration of the drug in repeated doses or in combination with other drugs might be necessary. PMID- 24211490 TI - Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice. AB - BACKGROUND & AIMS: In the enteric nervous system, neurotransmitters initiate changes in calcium (Ca(2+) responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca(2+)-mediated responses in enteric glia are required to maintain gastrointestinal function. METHODS: We used in situ Ca(2+) imaging to monitor glial Ca(2+) responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::CreER(T2+/-)/Cx43(f/f) mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription polymerase chain reaction analyses. RESULTS: Ca(2+) responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca(2+) responses. In vivo attenuation of Ca(2+) responses in the enteric glial network slowed gut transit overall and delayed colonic transit--these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca(2+)-mediated responses and changes in glial expression of Cx43 messenger RNA and protein. CONCLUSIONS: Ca(2+)-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders. PMID- 24211492 TI - Exposure to metals during pregnancy and neuropsychological development at the age of 4 years. AB - BACKGROUND: There is insufficient epidemiological evidence for deciding whether prenatal exposure to the current low-levels of metals in developed countries may affect neuropsychological function in early childhood. OBJECTIVES: Our goal was to evaluate potential neurotoxic effects of prenatal exposure to seven metals (cobalt, copper, arsenic, cadmium, antimony, thallium and lead), during the 1st and 3rd trimester of pregnancy, on child neuropsychological development at 4 years of age. MATERIALS AND METHODS: This study was based on a population-based birth cohort established in Sabadell (Catalonia, Spain) as part of the INMA [Environment and Childhood] Project. Metals were measured in 485 urine samples collected from mothers during the 1st and 3rd trimester of pregnancy. We assessed the neuropsychological development of 553 4-year-olds with the McCarthy Scales of Childrens' Abilitites (MSCA), together with their ADHD symptomatology, using the ADHD-DSM-IV criteria. A total of 385 children were included in the present study. RESULTS: We found no statistically significant associations between metals and general cognitive scale or executive function of the MSCA. We found negative coefficients for the exposure to cadmium 1st trimester, cadmium 3rd trimester and lead 3rd trimester on the general cognitive score of MSCA, although these results were not significant. We did not find any association between prenatal exposure to metals and ADHD symptomatology at the age of 4 years. CONCLUSIONS: Our results do not suggest that prenatal exposure to current low-levels of metals impairs children's cognitive development during preschool years. PMID- 24211493 TI - Review of therapeutic electrical stimulation for dorsiflexion assist and orthotic substitution from the American Congress of Rehabilitation Medicine stroke movement interventions subcommittee. AB - Ankle dorsiflexion weakness that impedes walking affects some 30% of people after a stroke, which increases the risk of falls and mortality. Recent advances in functional electrical stimulation or electrical stimulation orthotic substitute walking devices facilitate the use of surface electrode stimulation during therapeutic gait training and as an orthotic substitute. However, many therapists who could promote the use of these electrical stimulation orthotic substitute devices are not doing so, possibly because of a lack of knowledge about the devices and uncertainty about which patients could benefit from the devices but also because of a lack of reimbursement by some insurance providers. In addition, there is limited evidence about the efficacy of electrical stimulation orthotic substitute devices for therapeutic use or as a substitute for a traditional ankle foot orthosis (AFO). This article provides clinicians with information to guide them in the use of electrical stimulation orthotic substitute devices, discusses current research about the use of electrical stimulation orthotic substitute devices for therapeutic and orthotic purposes, and compares the use of electrical stimulation orthotic substitute devices and AFOs. There is insufficient evidence thus far to conclude that walking with an electrical stimulation orthotic substitute device is superior to walking with an AFO, but electrical stimulation orthotic substitute devices may be the optimal choice for some patients. PMID- 24211491 TI - Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators. AB - BACKGROUND & AIMS: Subgroups of colorectal carcinomas (CRCs) characterized by DNA methylation anomalies are termed CpG island methylator phenotype (CIMP)1, CIMP2, or CIMP-negative. The pathogenesis of CIMP1 colorectal carcinomas, and their effects on patients' prognoses and responses to treatment, differ from those of other CRCs. We sought to identify genetic somatic alterations associated with CIMP1 CRCs. METHODS: We examined genomic DNA samples from 100 primary CRCs, 10 adenomas, and adjacent normal-appearing mucosae from patients undergoing surgery or colonoscopy at 3 tertiary medical centers. We performed exome sequencing of 16 colorectal tumors and their adjacent normal tissues. Extensive comparison with known somatic alterations in CRCs allowed segregation of CIMP1-exclusive alterations. The prevalence of mutations in selected genes was determined from an independent cohort. RESULTS: We found that genes that regulate chromatin were mutated in CIMP1 CRCs; the highest rates of mutation were observed in CHD7 and CHD8, which encode members of the chromodomain helicase/adenosine triphosphate dependent chromatin remodeling family. Somatic mutations in these 2 genes were detected in 5 of 9 CIMP1 CRCs. A prevalence screen showed that nonsilencing mutations in CHD7 and CHD8 occurred significantly more frequently in CIMP1 tumors (18 of 42 [43%]) than in CIMP2 (3 of 34 [9%]; P < .01) or CIMP-negative tumors (2 of 34 [6%]; P < .001). CIMP1 markers had increased binding by CHD7, compared with all genes. Genes altered in patients with CHARGE syndrome (congenital malformations involving the central nervous system, eye, ear, nose, and mediastinal organs) who had CHD7 mutations were also altered in CRCs with mutations in CHD7. CONCLUSIONS: Aberrations in chromatin remodeling could contribute to the development of CIMP1 CRCs. A better understanding of the biological determinants of CRCs can be achieved when these tumors are categorized according to their epigenetic status. PMID- 24211494 TI - The effect of fusidic acid on Plasmodium falciparum elongation factor G (EF-G). AB - Inhibition of growth of the malaria parasite Plasmodium falciparum by known translation-inhibitory antibiotics has generated interest in understanding their action on the translation apparatus of the two genome containing organelles of the malaria parasite: the mitochondrion and the relic plastid (apicoplast). We report GTPase activity of recombinant EF-G proteins that are targeted to the organelles and further use these to test the effect of the EF-G inhibitor fusidic acid (FA) on the factor-ribosome interface. Our results monitoring locking of EF G.GDP onto surrogate Escherichia coli ribosomes as well as multi-turnover GTP hydrolysis by the factor indicate that FA has a greater effect on apicoplast EF-G compared to the mitochondrial counterpart. Deletion of a three amino acid (GVG) sequence in the switch I loop that is conserved in proteins of the mitochondrial EF-G1 family and the Plasmodium mitochondrial factor, but is absent in apicoplast EF-G, demonstrated that this motif contributes to differential inhibition of the two EF-Gs by FA. Additionally, the drug thiostrepton, that is known to target the apicoplast and proteasome, enhanced retention of only mitochondrial EF-G on ribosomes providing support for the reported effect of the drug on parasite mitochondrial translation. PMID- 24211495 TI - Effects of inhalable microparticle of flower of Lonicera japonica in a mouse model of COPD. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Flower of Lonicera japonica (FLJ) is a traditional herbal medicine widely used in East Asia as an anti-inflammatory and anti-oxidative agent. The purpose of this study is to develop an inhalable powder formulation of FLJ and to evaluate its biological effects in a mouse model of chronic obstructive pulmonary disease (COPD). METHODS: Inhalable dry powder containing FLJ was produced by spray-drying with leucine as an excipient. Its aerodynamic properties and anti-inflammatory activities were evaluated using the Anderson cascade impactor (ACI) and a mouse model of COPD, respectively. RESULTS: FLJ microparticle (FLJmp) had a hollow spherical shape in electron microscopy and showed aerodynamic properties suitable for inhalation (fine particle fraction of 54.0 +/- 4.68% and mass median aerodynamic diameter of 4.6 +/- 0.34MUm). FLJmp decreased TNF-alpha and IL-6 expression in RAW264.7 cells activated by lipopolysaccharide (LPS). In mice challenged with LPS and cigarette smoke solution (CSS) to develop COPD, FLJmp decreased the levels of TNF-alpha and IL-6 in bronchoalveolar fluidas well as the number of inflammatory cells including neutrophils in peripheral blood. In addition, FLJmp induced recovery of elastin and collagen distribution, reduction of caspase-3 expression in lung tissues of COPD mice. CONCLUSIONS: Inhalational delivery of FLJ using a microparticle system is a promising strategy for the treatment of COPD. PMID- 24211496 TI - Predictors of follow-up completeness in longitudinal research on traumatic brain injury: findings from the National Institute on Disability and Rehabilitation Research traumatic brain injury model systems program. AB - OBJECTIVE: To identify baseline participant variables in the domains of demographics, medical/psychosocial history, injury characteristics, and postinjury functional status associated with longitudinal follow-up completeness in persons with traumatic brain injury (TBI) using the TBI Model Systems (TBIMS) National Database (NDB). DESIGN: Exhaustive chi-square automatic interaction detection was used to identify factors that classified participants according to level of follow-up completeness. SETTING: Retrospective analysis of a multi center longitudinal database. PARTICIPANTS: Individuals (N=8249) enrolled in the TBIMS NDB between 1989 and 2009 who were eligible for at least the first (year 1) follow-up up to the fifth (year 15) follow-up. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Follow-up completeness as defined by 6 different longitudinal response patterns (LRPs): completing all follow-ups, wave nonresponse, dropping out, completing no follow-ups without formally withdrawing, formally withdrawing before completing any follow-ups, and formally withdrawing after completing some follow-ups. RESULTS: Completing all follow-ups was associated with higher levels of education, living with parents or others, and having acute care payer data entered in the NDB. Subgroups more vulnerable to loss to follow-up (LTFU) included those with less education, racial/ethnic minority backgrounds, those with better motor functioning on rehabilitation discharge, and those for whom baseline data on education, employment, and acute care payer were not collected. No subgroups were found to be more likely to have the LRPs of dropping out or formal withdrawal. CONCLUSIONS: These data identify subgroups in which retention strategies beyond those most commonly used might reduce LTFU in longitudinal studies of persons with TBI, such as the TBIMS, and suggest future investigations into factors associated with missing baseline data. PMID- 24211497 TI - Learning from 8 years of regional cyanobacteria observation in Brittany in view of sanitary survey improvement. AB - Cyanobacteria and cyanotoxins have been more and more studied during the last decades with regard to environment and health issues. More recently the consequences of climate change reinforced the need for research in view of a better management of cyanobacteria blooms. In this context the exploitation of the water quality survey of 26 recreational lakes in Brittany (north western France) between 2004 and 2011 is reported in this paper in order to encompass spatial and interannual patterns of cyanobacteria development at a regional scale. Starting from weekly data principally acquired during summertime, the links between cyanobacteria cell densities, toxin occurrences and interannual meteorological factors can give insights on the potential evolution of cyanobacterial crisis in the future. This study is part of a project aiming at a better understanding of potentially toxic cyanobacteria crisis occurrences in recreational waters, in order to improve predictive monitoring routines. PMID- 24211498 TI - Polychlorinated terphenyl patterns and levels in selected marine mammals and a river fish from different continents. AB - Polychlorinated terphenyls (PCTs) are a class of persistent organic pollutants which have been used from the 1920s to the 1980s for similar purposes as polychlorinated biphenyls (PCBs). Comparably little data was available on the PCT distribution in the environment mainly due to analytical difficulties in their determination. By means of a calculation algorithm recently developed we now studied the PCT pattern in individual marine mammal samples and one fish sample from different continents. Altogether, 97 PCTs were detected in eight samples and twelve to 66 tetra- to nonachloroterphenyl (tetra- to nonaCT) congeners were detected in individual samples. PCTs were present in all marine mammal samples which originated from four continents, but the PCT pattern was varied. TetraCTs were dominant in the sample from Africa, Australia, Spitsbergen (European Arctic) and in a sample from the Baltic Sea, heptaCTs in samples from the North Sea and octaCTs in a sample from Iceland. The abundance of sumPCTs relative to PCB 153, estimated from the GC/ECNI-MS response corrected for the degree of chlorination, ranged from 0.9 to 8.8%, corresponding with ~0.22-2.2% of the total PCB content. The highest PCT level detected was 980 mg/kg lipid in a harbour seal from the North Sea, Germany. The results from this study indicated that samples from certain areas, e.g. the North Sea may still be polluted with PCTs. PMID- 24211499 TI - Short-time windowed covariance: a metric for identifying non-stationary, event related covariant cortical sites. AB - BACKGROUND: Electrocorticography (ECoG) signals can provide high spatio-temporal resolution and high signal to noise ratio recordings of local neural activity from the surface of the brain. Previous studies have shown that broad-band, spatially focal, high-frequency increases in ECoG signals are highly correlated with movement and other cognitive tasks and can be volitionally modulated. However, significant additional information may be present in inter-electrode interactions, but adding additional higher order inter-electrode interactions can be impractical from a computational aspect, if not impossible. NEW METHOD: In this paper we present a new method of calculating high frequency interactions between electrodes called Short-Time Windowed Covariance (STWC) that builds on mathematical techniques currently used in neural signal analysis, along with an implementation that accelerates the algorithm by orders of magnitude by leveraging commodity, off-the-shelf graphics processing unit (GPU) hardware. RESULTS: Using the hardware-accelerated implementation of STWC, we identify many types of event-related inter-electrode interactions from human ECoG recordings on global and local scales that have not been identified by previous methods. Unique temporal patterns are observed for digit flexion in both low- (10mm spacing) and high-resolution (3mm spacing) electrode arrays. COMPARISON WITH EXISTING METHODS: Covariance is a commonly used metric for identifying correlated signals, but the standard covariance calculations do not allow for temporally varying covariance. In contrast STWC allows and identifies event-driven changes in covariance without identifying spurious noise correlations. CONCLUSIONS: STWC can be used to identify event-related neural interactions whose high computational load is well suited to GPU capabilities. PMID- 24211501 TI - Deconstructing stent polymers. PMID- 24211500 TI - Vorapaxar in acute coronary syndrome patients undergoing coronary artery bypass graft surgery: subgroup analysis from the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome). AB - OBJECTIVES: This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG). BACKGROUND: Platelet activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients. METHODS: Associations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method. RESULTS: Among 12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization during index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%). CONCLUSIONS: In non-ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome [TRA.CER] [Study P04736AM3]; NCT00527943). PMID- 24211502 TI - Underexpansion and ad hoc post-dilation in selected patients undergoing balloon expandable transcatheter aortic valve replacement. AB - OBJECTIVES: This study sought to assess the clinical outcomes and hemodynamic performance associated with a strategy of underexpanding balloon-expandable transcatheter heart valves (THV) when excessive oversizing is a concern. BACKGROUND: Transcatheter aortic valve replacement depends on the selection of an optimally sized THV. An undersized THV may lead to paravalvular regurgitation, whereas excessive oversizing may lead to annular injury. METHODS: Patients (n = 47) who underwent transcatheter aortic valve replacement with an intentionally underexpanded THV (balloon-filling volume reduced ~10%) were compared with consecutive control patients who had nominal THV balloon deployment (n = 87). Pre and post-procedural computed tomography imaging and echocardiography were performed to assess THV stent expansion and hemodynamics. RESULTS: Underfilling resulted in THV underexpansion that was maximal at the THV inflow (85.0 +/- 7.4% vs. 102.5 +/- 6.2%, p < 0.001), in study versus control groups, respectively. The study group received larger THV, although annular injury was not observed. Post dilation was required in 10.6% and 4.6% of patients of the study and control groups, respectively (p = 0.165). Echocardiographic THV area, gradient, paravalvular regurgitation, and in-hospital outcomes were similar. CONCLUSIONS: Intentionally underexpanding balloon-expandable THV by underfilling the deployment balloon did not adversely affect procedural clinical outcomes, THV gradients, or THV areas. A strategy of underexpansion, with post-dilation as necessary, might play in role in reducing the risk of annular injury and paravalvular regurgitation in selected patients. PMID- 24211504 TI - Resting versus vasodilated pressure gradients in assessing stenosis severity. PMID- 24211503 TI - Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. AB - OBJECTIVES: This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study. BACKGROUND: FFR is an index of the severity of coronary stenosis that has been clinically validated in 3 prospective randomized trials. iFR and Pd/Pa are nonhyperemic pressure-derived indices of the severity of stenosis with discordant reports regarding their accuracy with respect to FFR. METHODS: iFR, resting Pd/Pa, and FFR were measured in 1,768 patients from 15 clinical sites. An independent physiology core laboratory performed blinded off-line analysis of all raw data. The primary objectives were to determine specific iFR and Pd/Pa thresholds with >=90% accuracy in predicting ischemic versus nonischemic FFR (on the basis of an FFR cut point of 0.80) and the proportion of patients falling beyond those thresholds. RESULTS: Of 1,974 submitted lesions, 381 (19.3%) were excluded because of suboptimal acquisition, leaving 1,593 for final analysis. On receiver-operating characteristic analysis, the optimal iFR cut point for FFR <=0.80 was 0.90 (C statistic: 0.81 [95% confidence interval: 0.79 to 0.83]; overall accuracy: 80.4%) and for Pd/Pa was 0.92 (C statistic: 0.82 [95% confidence interval: 0.80 to 0.84]; overall accuracy: 81.5%), with no significant difference between these resting measures. iFR and Pd/Pa had >=90% accuracy to predict a positive or negative FFR in 64.9% (62.6% to 67.3%) and 48.3% (45.6% to 50.5%) of lesions, respectively. CONCLUSIONS: This comprehensive core laboratory analysis comparing iFR and Pd/Pa with FFR demonstrated an overall accuracy of ~80% for both nonhyperemic indices, which can be improved to >=90% in a subset of lesions. Clinical outcome studies are required to determine whether the use of iFR or Pd/Pa might obviate the need for hyperemia in selected patients. PMID- 24211505 TI - Giant neonatal cardiac tumor: unusual presentation and natural history. PMID- 24211506 TI - Prospective multicenter evaluation of the direct flow medical transcatheter aortic valve. AB - OBJECTIVES: The study sought a prospective multicenter nonrandomized evaluation of the Direct Flow Medical (DFM) system for the treatment of severe aortic stenosis. BACKGROUND: The DFM transcatheter aortic valve system is a nonmetallic design with a pressurized support structure that allows precise positioning, retrieval, and assessment of valve performance prior to permanent implantation. METHODS: One hundred high surgical risk patients with severe aortic stenosis were evaluated for the primary endpoint. There were 75 patients in the group evaluable for the secondary endpoints and 25 in the pre-specified roll-in training phase. Echocardiographic and angiographic data were evaluated by an independent core laboratory and adverse events adjudicated by clinical event committee and classified according to Valve Academic Research Consortium (VARC) criteria. RESULTS: There was 99% freedom from all cause mortality at 30 days (primary endpoint). VARC criteria defined 30 day combined freedom from patient safety event rate was 91% and overall device success was 93%. The post-implantation echocardiography results demonstrated mild or no aortic regurgitation in 99% (73 of 74) with a mean gradient of 12.6 +/- 7.1 mm Hg (n = 72) and effective orifice area of 1.50 +/- 0.56 cm(2) and New York Heart Association functional class was I or II in 92% of cases. CONCLUSIONS: The present study demonstrates the safety and efficacy of the DFM system in surgical high risk patients with severe aortic stenosis and complex anatomy aortic regurgitation was less than moderate in 99% of patients. PMID- 24211507 TI - Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug eluting and bare-metal stents: evidence from a comprehensive network meta analysis. AB - OBJECTIVES: This study sought to investigate the relative safety and efficacy of bioabsorbable polymer (BP)-based biolimus-eluting stents (BES) versus durable polymer (DP)-drug-eluting stents (DES) and bare-metal stents (BMS) by means of a network meta-analysis. BACKGROUND: Studies have suggested that BP-BES might reduce the risk of stent thrombosis (ST) and late adverse outcomes compared with first-generation DES. However, the relative safety and efficacy of BP-BES versus newer-generation DES coated with more biocompatible DP have not been investigated in depth. METHODS: Randomized controlled trials comparing BP-BES versus currently U.S.-approved DES or BMS were searched through MEDLINE, EMBASE, and Cochrane databases. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. RESULTS: Data from 89 trials including 85,490 patients were analyzed. At 1-year follow-up, BP-BES were associated with lower rates of cardiac death/myocardial infarction (MI), MI, and target vessel revascularization (TVR) than BMS and lower rates of TVR than fast release zotarolimus-eluting stents. The BP-BES had similar rates of cardiac death/MI, MI, and TVR compared with other second-generation DP-DES but higher rates of 1-year ST than cobalt-chromium everolimus-eluting stents (CoCr-EES). The BP-BES were associated with improved late outcomes compared with BMS and paclitaxel-eluting stents, considering the latest follow-up data available, with nonsignificantly different outcomes compared with other DP-DES although higher rates of definite ST compared with CoCr-EES. CONCLUSIONS: In this large-scale network meta-analysis, BP-BES were associated with superior clinical outcomes compared with BMS and first-generation DES and similar rates of cardiac death/MI, MI, and TVR compared with second-generation DP-DES but higher rates of definite ST than CoCr-EES. PMID- 24211509 TI - Cardioversion with novel oral anticoagulants: reconfirming a 50-year-old standard. PMID- 24211508 TI - Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). AB - OBJECTIVES: The aim of this study was to determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa inhibitor, compared with warfarin. BACKGROUND: In patients with atrial fibrillation, thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. METHODS: Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, we conducted a post-hoc analysis of patients undergoing cardioversion. RESULTS: A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those assigned to warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 +/- 231 days and 251 +/- 248 days, respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30-day follow-up period. Myocardial infarction occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). CONCLUSIONS: Major cardiovascular events after cardioversion of atrial fibrillation are rare and comparable between warfarin and apixaban. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984). PMID- 24211510 TI - A randomized controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease. AB - OBJECTIVES: The aim of this randomized placebo-controlled trial was to determine if withdrawing clopidogrel therapy leads to increased platelet activity compared with pre-treatment values in patients with stable coronary artery or peripheral arterial disease. BACKGROUND: Reports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity. METHODS: In all, 171 patients receiving established aspirin therapy were randomly assigned to placebo or clopidogrel (75 mg daily) for 28 days. Blood samples were taken at pre-treatment baseline, on treatment just before discontinuation of study drug, and on days 7, 14, and 28 after discontinuation. The primary outcome measure was adenosine diphosphate (ADP)-stimulated platelet fibrinogen binding. Six secondary outcomes were assessed: ADP-stimulated platelet P-selectin, unstimulated platelet fibrinogen binding, and light transmission aggregometry with ADP 5 and 10 MUmol/l recorded at maximum and at 6 min. RESULTS: The ADP-stimulated platelet fibrinogen binding, P-selectin expression, and platelet aggregation were lower on treatment with clopidogrel compared with baseline (p < 0.0001), but returned to baseline levels by 7 days after discontinuation. Mixed model analyses excluding the on treatment timepoint showed no overall differences between the clopidogrel and placebo groups (p > 0.05). Furthermore, there was no evidence of an interaction between platelet inhibition over time and treatment allocation. CONCLUSIONS: This trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299). PMID- 24211511 TI - Towards a unified model of passive drug permeation I: origins of the unstirred water layer with applications to ionic permeation. AB - In this work, we provide a unified theoretical framework describing how drug molecules can permeate across membranes in neutral and ionized forms for unstirred in vitro systems. The analysis provides a self-consistent basis for the origin of the unstirred water layer (UWL) within the Nernst-Planck framework in the fully unstirred limit and further provides an accounting mechanism based simply on the bulk aqueous solvent diffusion constant of the drug molecule. Our framework makes no new assumptions about the underlying physics of molecular permeation. We hold simply that Nernst-Planck is a reasonable approximation at low concentrations and all physical systems must conserve mass. The applicability of the derived framework has been examined both with respect to the effect of stirring and externally applied voltages to measured permeability. The analysis contains data for 9 compounds extracted from the literature representing a range of permeabilities and aqueous diffusion coefficients. Applicability with respect to ionized permeation is examined using literature data for the permanently charged cation, crystal violet, providing a basis for the underlying mechanism for ionized drug permeation for this molecule as being due to mobile counter current flow. PMID- 24211512 TI - Traumatic lumbar visceral herniation in a young woman. AB - INTRODUCTION: Lumbar herniation is uncommon, with traumatic etiology being rare. Traumatic lumbar hernias are usually caused by seatbelt injury in motor vehicle accidents. It is exceedingly uncommon to see lumbar hernias in an unrestrained passenger of a motor vehicle accident. PRESENTATION OF CASE: We present a case of a traumatic inferior lumbar hernia in a young woman who was an unrestrained driver of a vehicle involved in a high-speed collision, with multiple rollover and ejection. CT scans of the abdomen and pelvis suggested soft tissue injury involving muscles in the left lower posterior flank with traumatic herniation of the colon and small bowel. Emergent midline abdominal laparotomy confirmed herniation in the left lower quadrant. After abdominal closure, in the prone position, an extensive laceration over the left flank also confirmed herniation. Due to its dirty nature, the wound was irrigated, lavaged and covered with wound vacuum-assisted closure placement. The decision was made in favor of delayed elective hernia repair. DISCUSSION: Lumbar hernias are usually caused by sudden force to the abdomen, leading to increased intra-abdominal pressure. This pressure combined with areas of weakness in the superior and/or inferior triangle lead to herniation. Uncommonly, the contents of lumbar hernias can strangulate or incarcerate leading to bowel obstruction. This can often be prevented by detection with CT and laparotomy. CONCLUSION: Lumbar herniation of traumatic etiology is rare. Early detection with CT and/or exploratory laparotomy is important to avoid increases in size of the defect and bowel strangulation and incarceration. PMID- 24211513 TI - Effects of calcium on rhizotoxicity and the accumulation and translocation of copper by grapevines. AB - We assessed the effects of background concentrations of calcium (Ca) in solution on rhizotoxicity of copper (Cu) in and the accumulation and translocation of Cu by the grapevine, Vitis vinifera L. var. Kyoho. Grapevine cuttings in a hydroponic system were exposed to Cu-spiked solutions (0, 1, 2.5, 5, 10, and 25 MUM) with two Ca backgrounds (0.5 and 5 mM) for 15 days. We found that when Cu exposure exceeded 5 MUM, no new white roots were generated from the cuttings. When exposed to a Cu concentration of 25 MUM, the lateral roots were sparse, appeared dark and exhibited malformed terminal swellings. The morphological phenomena of root response to an increase in Cu levels were relatively pronounced at a background concentration of 5 mM Ca; epidermal cell walls thickened, cortical cells remained intact and root terminal swelling was enhanced with Cu exposure. A 5 mM Ca background concentration enhanced the reduction in relative root elongation, but alleviated the reduction in relative root dry weight with increased Cu exposure. Moreover, there was a prominent increase in root Cu concentrations with increased Cu exposure, but the increases in leaf Cu concentrations were much less. The Cu profile of Cu exposure in a 5 mM Ca background concentration appeared higher in root, but lower in leaf than the Cu profile in a 0.5 mM Ca background; therefore, increase of Ca background concentrations would enhance Cu to be accumulated by root, but not translocated into the leaf. PMID- 24211514 TI - Associations between neighborhood characteristics and self-rated health: a cross sectional investigation in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. AB - Quantifying the effects of specific neighborhood features on self-reported health is important in understanding the global health impact of neighborhood context. We investigated associations of neighborhood poverty, sociability and walkability with self-rated physical and mental health in the Multi-Ethnic Study of Atherosclerosis (MESA). In separate models, each neighborhood variable was associated with physical health but associations with sociability and walkability were stronger than those for poverty. Only walkability remained significant after adjusting for the other neighborhood variables. There was no evidence that self rated mental health as assessed by the SF12 was associated with neighborhood poverty, walkability or sociability. This study provides information on how neighborhood context is associated with global health in diverse midlife and older persons. PMID- 24211515 TI - The evolution of centipede venom claws - open questions and possible answers. AB - The maxilliped venom claw is an intriguing structure in centipedes. We address open questions concerning this structure. The maxillipeds of fossil centipedes from the Carboniferous (about 300 million years old) have been described, but not been depicted previously. Re-investigation demonstrates that they resemble their modern counterparts. A Jurassic geophilomorph centipede (about 150 million years old) was originally described as possessing a rather leg-like maxilliped. Our re investigation shows that the maxilliped is, in fact, highly specialized as in modern Geophilomorpha. A scenario for the evolution of the centipede maxilliped is presented. It supports one of the two supposed hypotheses of centipede phylogeny, the Pleurostigmophora hypothesis. Although this hypothesis appears now well established, many aspects of character evolution resulting from this phylogeny remain to be told in detail. One such aspect is the special joint of the maxilliped in some species of Cryptops. Cryptops is an in-group of Scolopendromorpha, but its maxilliped joint can resemble that of Lithobiomorpha or even possess a mixture of characters between the both. Detailed investigation of fossils, larger sample sizes of extant species, and developmental data will be necessary to allow further improvements of the reconstruction of the evolutionary history of centipedes. PMID- 24211516 TI - Structure and distribution of antennal sensilla in Oranmorpha guerinii (Gervais, 1837) (Diplopoda, Polydesmida). AB - Detailed information on sensory organs of Diplopoda especially on antennal sensilla are still sparse and fragmentary. The present study on the antennae of Oranmorpha guerinii (Polydesmida, Paradoxosomatidae) utilizing scanning electron microscopy revealed the presence of six sensillar types: (1) apical cones, (2) sensilla trichodea, (3) sensilla microtrichodea, (4) sensilla chaetica, (5) sensilla basiconica bacilliformia, and (6) sensilla basiconica spiniformia. External structure and distribution of cuticular antennal sensilla are compared with data from other diplopod species. We moreover discuss possible functions of antennal sensilla in millipedes. PMID- 24211517 TI - Giant spermatozoa and a huge spermatheca: a case of coevolution of male and female reproductive organs in the ground louse Zorotypus impolitus (Insecta, Zoraptera). AB - The male and female genital apparatus of the recently discovered ground louse Zorotypus impolitus were examined using light and electron microscopy. The rounded testes and a large seminal vesicle are connected with a complex of four accessory glands by a long tapering ejaculatory duct. Two accessory glands have the same whitish coloration, whereas the third one is pale blue, and the elongated and cylindrical fourth one translucent. The sperm are the largest known in Hexapoda, 3mm long and 3MUm wide, with a volume of ca. 21,000MUm(3); the ratio between the diameter of the axoneme and the width of the main body of the sperm ranges between 1:10 and 1:13. The exceptional width of the spermatozoa is due to an extreme enlargement of the mitochondrial derivatives and accessory bodies. A single sperm is contained in a small globular spermatophore (100MUm). The highly unusual external transfer correlates with an atypical mating behavior. The male produces several to many spermatophores during the mating process. As in other zorapterans the ovaries are panoistic and the eggs bear two micropyles. An exceptionally large apical spermathecal receptacle is present; it is connected with the vagina by a long spermathecal duct, which varies structurally along its course. A correlation between the sperm size and the size of the spermatheca is likely. Ultrastructural features of different species support two strikingly different models of male and female reproductive apparatus in the small order Zoraptera. This is in stark contrast to the extreme uniformity of their external morphology. It is likely that sexual selection played a decisive role in the evolution of the reproductive system. PMID- 24211518 TI - Plasma proteomics, the Human Proteome Project, and cancer-associated alternative splice variant proteins. AB - This article addresses three inter-related subjects: the development of the Human Plasma Proteome Peptide Atlas, the launch of the Human Proteome Project, and the emergence of alternative splice variant transcripts and proteins as important features of evolution and pathogenesis. The current Plasma Peptide Atlas provides evidence on which peptides have been detected for every protein confidently identified in plasma; there are links to their spectra and their estimated abundance, facilitating the planning of targeted proteomics for biomarker studies. The Human Proteome Project (HPP) combines a chromosome-centric C-HPP with a biology and disease-driven B/D-HPP, upon a foundation of mass spectrometry, antibody, and knowledgebase resource pillars. The HPP aims to identify the approximately 7000 "missing proteins" and to characterize all proteins and their many isoforms. Success will enable the larger research community to utilize newly-available peptides, spectra, informative MS transitions, and databases for targeted analyses of priority proteins for each organ and disease. Among the isoforms of proteins, splice variants have the special feature of greatly enlarging protein diversity without enlarging the genome; evidence is accumulating of striking differential expression of splice variants in cancers. In this era of RNA-sequencing and advanced mass spectrometry, it is no longer sufficient to speak simply of increased or decreased expression of genes or proteins without carefully examining the splice variants in the protein mixture produced from each multi-exon gene. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. PMID- 24211519 TI - Role of NADPH oxidase-4 in saturated fatty acid-induced insulin resistance in SK Hep-1 cells. AB - We aimed to develop a cell culture model of type 2 diabetes by treating SK-Hep-1 cells with four free fatty acids [i.e., palmitic acid, stearic acid (SA), linoleic acid and oleic acid]. The results showed that Akt phosphorylation was increased in SK-Hep-1 cells treated with insulin in a time- and concentration dependent manner, which was inhibited by saturated fatty acids, but not by unsaturated fatty acids. Moreover, protein levels of NADPH oxidase (NOX) 4 but not NOX2 were increased following SA treatment and, consequently, increased reactive oxygen species production and decreased cellular glutathione were observed. Apocynin, a NOX4 inhibitor, restored the SA-induced inhibition of Akt phosphorylation, suggesting the role of NOX4 in insulin resistance induced by SA. Neither phosphorylation level nor protein level of the stress signaling kinases, such as c-Jun N-terminal kinase or p38 mitogen activated protein kinase, was changed by SA treatment. Although binding immunoglobulin protein, a marker of endoplasmic reticulum stress, was transiently increased in SKHep-1 cells treated with SA, 4-phenyl butyric acid, a chemical chaperone, had no effect on the insulin-mediated Akt phosphorylation inhibited by SA. The present study provides a useful model for screening anti-insulin resistance drugs and finding new drug targets for treatment of diabetes. PMID- 24211520 TI - Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-kappaB/MAPKs pathway. AB - Gomisin A, one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill., has proved to possess a variety of pharmacological effects. The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms. It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity. Gomisin A was also able to attenuate the mRNA expression and the production of pro-inflammatory factors TNF-alpha, IL-1beta and IL-6. Moreover, LPS induced reactive oxygen species (ROS) production, NADPH oxidase activation, and gp91phox expression, which were markedly inhibited by gomisin A in microglia. Furthermore, the data showed that gomisin A significantly down-regulated the TLR4 protein expression, and inhibited nuclear transcription factor (NF)-kappaB and mitogen activated protein kinases (MAPKs) signaling pathways. Additionally, gomisin A alleviated the cell death of SH-SY5Y neuroblastoma, rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia. In summary, gomisin A may exert neuroprotective effects by attenuating the microglia mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-kappaB and MAPKs signaling pathways. PMID- 24211521 TI - A novel proteoglycan from Ganoderma lucidum fruiting bodies protects kidney function and ameliorates diabetic nephropathy via its antioxidant activity in C57BL/6 db/db mice. AB - Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. Thus, antidiabetic drugs with protection potential in the kidneys would have a higher therapeutic value. The effects of a novel proteoglycan, named FYGL, isolated from G. lucidum fruiting bodies, on the kidney function were investigated systematically in present work. FYGL (250 mg/kg) not only dosedependently reduced the blood glucose concentration (23.5%, p<0.05), kidney/body weight ratio (23.6%, p<0.01), serum creatinine (33.1%, p<0.01), urea nitrogen (24.1%, p<0.01),urea acid contents (35.9%, p<0.01) and albuminuria (30.7%, p<0.01)of DN mice compared to the untreated DN mice but also increased the renal superoxide dismutase (75.3%, p<0.01), glutathione peroxidase (35.0%, p<0.01) and catalase activities (58.5%, p<0.01) compared to the untreated DN mice. The decreasing of renal malondialdehyde content (34.3%, p<0.01) and 8 hydroxy-2'-deoxyguanosine expression (2.5-fold, p<0.01) were also observed in FYGL-treated DN mice compared to the untreated DN mice, along with an amelioration of renal morphologic abnormalities. We conclude that FYGL confers protection against the renal functional and morphologic injuries by increasing activities of antioxidants and inhibiting accumulation of oxidation, suggesting a potential nutritional supplement for the prevention and therapy of DN. PMID- 24211522 TI - Heterogeneity in background fitness acts as a suppressor of selection. AB - We introduce the concept of heterogeneity in background fitness to evolutionary dynamics in finite populations. Background fitness is specific to an individual but not linked to its strategy. It can be thought of as a property that is related to the physical or societal position of an individual, but is not dependent on the strategy that is adopted in the evolutionary process under consideration. In our model, an individual's total fitness is the sum of its background fitness and the fitness derived from using a specific strategy. This approach has important implications for the imitation of behavioural strategies: if we imitate others for their success, but can only adopt their behaviour and not their social and economic ties, we may imitate in vain. We study the effect of heterogeneity in background fitness on the fixation of a mutant strategy with constant fitness. We find that heterogeneity suppresses selection, but also decreases the time until a novel strategy either takes over the population or is lost again. We derive analytical solutions of the fixation probability in small populations. In the case of large total background fitness in a population with maximum inequality, we find a particularly simple approximation of the fixation probability. Numerical simulations suggest that this simple approximation also holds for larger population sizes. PMID- 24211523 TI - Assessing cytokines' talking patterns following experimental myocardial damage by applying Shannon's information theory. AB - BACKGROUND: The simultaneous measurement of multiple cytokines in parallel by using multiplex proteome arrays (MPA) is of great interest to understanding the inflammatory response following myocardial infarction; however, since cytokines are pleiotropic and redundant, increase of information throughput (IT) attained by measuring multiple cytokines remain to be determined. We aimed this study to assess the IT of an MPA system designed to assess 8 cytokines - commercially available at the time of the study - serum levels, before (control state) and after experimental myocardial cryoinjury (activated state) in rats. METHODS: By assuming that redundant information do not generally increase the IT, we derived Entropy (H) and Redundancy (R) of information by using formulas of Shannon modified accordingly, where a high IT (high H and low R) corresponds to a low level of correlation between cytokines and vice versa for a low IT. The maximum theoretical level of IT and the contribution of each cytokine were also estimated. RESULTS: In control state, no significant correlations were found between cytokines showing high IT; on the contrary, in activated state, several significant correlations were found supporting a complex cross-talk pattern between cytokines with low IT. Using as reference the maximum theoretical level of IT, in activated state, H was reduced of 67.0% and R was increased of 77.4% supporting a reduction of IT. Furthermore, the contribution of individual cytokines to H value of MPA was variable: in control state, IL-2 gave the most contribution to H value, conversely during activated state IL-10 gave most contribution. Finally during activated state, IL-1beta was the only cytokine strongly correlated with values of all other cytokines, suggesting a crucial role in the inflammatory cascade. CONCLUSIONS: Paradoxically, by analyzing an MPA system designed for redundant analytes such as cytokines, translating the Shannon's information theory from the field of communication to biology, the IT system in our model deteriorates during the activation state by increasing its redundancy, showing maximum value of entropy in the control conditions. Finally, the study of the mutual interdependence between cytokines by the contribution to the IT may allow formulating alternative models to describe the inflammatory cascade after myocardial infarction. PMID- 24211524 TI - pH feedback and phenotypic diversity within bacterial functional groups of the human gut. AB - Microbial diversity in the human colon is very high with apparently large functional redundancy such that within each bacterial functional group there are many coexisting strains. Modelling this mathematically is problematic since strains within a functional group are often competing for the same limited number of resources and therefore competitive exclusion theory predicts a loss of diversity over time. Here we investigate, through computer simulation, a fluctuation dependent mechanism for the promotion of diversity. A variable pH environment caused by acidic by-products of bacterial growth on a fluctuating substrate coupled with small differences in acid tolerance between strains promotes diversity under both equilibrium and far-from-equilibrium conditions. Under equilibrium conditions pH fluctuations and relative nonlinearity in pH limitation among strains combine to prevent complete competitive exclusion. Under far-from-equilibrium conditions, loss of diversity through extinctions is made more difficult because pH cycling leads to fluctuations in the competitive ranking of strains, thereby helping to equalise fitness. We assume a trade-off between acid tolerance and maximum growth rate so that our microbial system consists of strains ranging from specialists to generalists. By altering the magnitude of the effect of the system on its pH environment (e.g. the buffering capacity of the colon) and the pattern of incoming resource we explore the conditions that promote diversity. PMID- 24211525 TI - Prediction of FMN-binding residues with three-dimensional probability distributions of interacting atoms on protein surfaces. AB - Flavin mono-nucleotide (FMN) is a cofactor which is involved in many biological reactions. The insights on protein-FMN interactions aid the protein functional annotation and also facilitate in drug design. In this study, we have established a new method, making use of an encoding scheme of the three-dimensional probability density maps that describe the distributions of 40 non-covalent interacting atom types around protein surfaces, to predict FMN-binding sites on protein surfaces. One machine learning model was trained for each of the 30 protein atom types to predict tentative FMN-binding sites on protein structures. The method's capability was evaluated by five-fold cross-validation on a dataset containing 81 non-redundant FMN-binding protein structures and further tested on independent datasets of 30 and 15 non-redundant protein structures respectively. These predictions achieved an accuracy of 0.94, 0.94 and 0.96 with the Matthews correlation coefficient (MCC) of 0.53, 0.53 and 0.65 respectively for the three protein structure sets. The prediction capability is superior to the existing method. This is the first structure-based approach that does not rely on evolutionary information for predicting FMN-interacting residues. The webserver for the prediction is available at http://ismblab.genomics.sinica.edu.tw/. PMID- 24211526 TI - The evolutionary and behavioral modification of consumer responses to environmental change. AB - How will evolution or other forms of adaptive change alter the response of a consumer species' population density to environmentally driven changes in population growth parameters? This question is addressed by analyzing some simple consumer-resource models to separate the ecological and evolutionary components of the population's response. Ecological responses are always decreased population size, but evolution of traits that have effects on both resource uptake rate and another fitness-related parameter may magnify, offset, or reverse this population decrease. Evolution can change ecologically driven decreases in population size to increases; this is likely when: (1) resources are initially below the density that maximizes resource growth, and (2) the evolutionary response decreases the consumer's resource uptake rate. Evolutionary magnification of the ecological decreases in population size can occur when the environmental change is higher trait-independent mortality. Such evolution-driven decreases are most likely when uptake-rate traits increase and the resource is initially below its maximum growth density. It is common for the difference between the new eco-evolutionary equilibrium and the new ecological equilibrium to be larger than that between the original and new ecological equilibrium densities. The relative magnitudes of ecological and evolutionary effects often depend sensitively on the magnitude of the environmental change and the nature of resource growth. PMID- 24211527 TI - Molecular modeling, simulation and virtual screening of ribosomal phosphoprotein P1 from Plasmodium falciparum. AB - Ribosomal phosphoprotein P1 (RPP1) is acidic phosphoprotein which in association with neutral phosphoprotein P0 and acidic phosphoprotein P2 forms ribosomal P protein complex as (P1)2-P0-(P2)2. P protein is known to be immunogenic and has important role in protein translation. 3D structure of P1 is not known. We have built an ab-initio model of RPP1 of Plasmodium falciparum using I-TASSER. Stereochemical stability of structure was checked using PROCHECK and the normality of the local environment of amino acids was checked using WHATIF. Comparison between known protein structures in PDB database and model protein was done using Dali server. Molecular dynamic simulation study and virtual screening of RPP1 was carried out. Three dimensional model structure of RPP1 was generated and model validation studies proved the model to be steriochemically significant. RPP1 structure was found to be stable at room temperature in water environment demonstrated by 30 ns molecular dynamic simulation study. Dali superimposition showed 69% superimposition to known 3D structures in PDB. Further virtual screening and docking studies promoted good interaction of ligands Ecgonine, Prazepam and Ethyl loflazepate with RPP1. The work provides insight for molecular understanding of RPP1 of P. falciparum and can be used for development of antimalarial drugs. PMID- 24211528 TI - Sub-categorisation of skin corrosive chemicals by the EpiSkinTM reconstructed human epidermis skin corrosion test method according to UN GHS: revision of OECD Test Guideline 431. AB - The EpiSkinTM skin corrosion test method was formally validated and adopted within the context of OECD TG 431 for identifying corrosive and non-corrosive chemicals. The EU Classification, Labelling and Packaging Regulation (EU CLP) system requires the sub-categorisation of corrosive chemicals into the three UN GHS optional subcategories 1A, 1B and 1C. The present study was undertaken to investigate the usefulness of the validated EpiSkinTM test method to identify skin corrosive UN GHS Categories 1A, 1B and 1C using the original and validated prediction model and adapted controls for direct MTT reduction. In total, 85 chemicals selected by the OECD expert group on skin corrosion were tested in three independent runs. The results obtained were highly reproducible both within (>80%) and between (>78%) laboratories when compared with historical data. Moreover the results obtained showed that the EpiSkinTM test method is highly sensitive (99%) and specific (80%) in discriminating corrosive from non-corrosive chemicals and allows reliable and relevant identification of the different skin corrosive UN GHS subcategories, with high accuracies being obtained for both UN GHS Categories 1A (83%) and 1B/1C (76%) chemicals. The overall accuracy of the test method to subcategorise corrosive chemicals into three or two UN GHS subcategories ranged from 75% to 79%. Considering those results, the revised OECD Test Guideline 431 permit the use of EpiSkinTM for subcategorising corrosive chemicals into at least two classes (Category 1A and Category 1B/1C). PMID- 24211529 TI - Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells. AB - Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50MUm and around 95% at 500MUM of ATZ (p<0.01). This gene encodes the protein S100a4 and is a clinical biomarker of epithelial-mesenchymal transition (EMT), a key step in the metastatic process. Here we investigated the possible effect of ATZ on cell migration and noticed that it prevents the EMT and motility of the HepG2 cells induced by the phorbol ester TPA. ATZ decreases Fak pathway activation but has no effect on the Erk1/2 pathway known to be involved in metastasis in this cell line. These results suggest that ATZ could be involved in cell homeostasis perturbation, potentially through a S100a4-dependant mechanism. PMID- 24211530 TI - Gene expressions changes in bronchial epithelial cells: markers for respiratory sensitizers and exploration of the NRF2 pathway. AB - For the classification of respiratory sensitizing chemicals, no validated in vivo nor in vitro tests are currently available. In this study, we evaluated whether respiratory sensitizers trigger specific signals in human bronchial epithelial (BEAS-2B) cells at the level of the transcriptome. The cells were exposed during 6, 10, and 24h to 4 respiratory sensitizers and 6 non-respiratory sensitizers (3 skin sensitizers and 3 respiratory irritants) at a concentration inducing 20% cell viability loss after 24h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4*44K oligonucleotide arrays. A limited number of 11 transcripts could be identified as potential biomarkers to identify respiratory sensitizers. Three of these transcripts are associated to immune system processes (HSPA5, UPP1, and SEPRINE1). In addition, the transcriptome was screened for transcripts that are differentially expressed compared to vehicle control for each chemical. The results show that the NRF2-mediated oxidative stress response is activated in the cell line after stimulation with all of the chemicals that were selected in our study, and that - at the level of gene expression - this pathway shows no potential to discriminate between any of the three compound groups: respiratory sensitizers, skin sensitizers, or electrophilic respiratory irritants. PMID- 24211531 TI - Role of size and surface area for pro-inflammatory responses to silica nanoparticles in epithelial lung cells: importance of exposure conditions. AB - The present study compared non-crystalline silica particles of nano (50nm)- and submicro (500nm)-size (Si50 and Si500) for the potential to induce cytokine responses in bronchial epithelial lung cells (BEAS-2B). The cell cultures were exposed to equal mass and surface area concentrations of the two particles in different exposure media; LHC-9 and DMEM:F12. The state of agglomeration was different in the two media; with marked agglomeration in LHC-9 and nearly no agglomeration in DMEM:F12. On a mass basis, Si50 was more potent than Si500 in inducing cytokine responses in both exposure media. In contrast, upon exposure to similar surface area concentrations, Si500 was more potent than Si50 in DMEM:F12. This might be due to different agglomeration/sedimentation properties of Si50 versus Si500 in the two media. However, influence of differences in particle reactivity or particle uptake cannot be excluded. The data indicated no qualitative changes in the cytokine gene-expression patterns induced by the two particles, suggesting effects through similar mechanisms. These aspects might be of importance for interpretation of in vitro studies of nanomaterials. PMID- 24211532 TI - Development and validation of an open source O2-sensitive gel for physiological profiling of soil microbial communities. AB - Community level physiological profiling is a simple, high-throughput technique for assessing microbial community physiology. Initial methods relying on redox dye based detection of respiration were subject to strong enrichment bias, but subsequent development of a microtiter assay using an oxygen-quenched dye reduced this bias and improved the versatility of the approach. Commercial production of the oxygen microplates recently stopped, which led to the present effort to develop and validate a system using a luminophore dye (platinum tetrakis pentafluorophenyl) immobilized at the bottom of wells within a 96 well microtiter plate. The technique was used to analyze three well-characterized Florida soils: oak saw palmetto scrub, coastal mixed hardwood, and soil from an agricultural field used to grow corn silage. Substrate induced respiration was monitored by measuring respiration rates in soils under basal conditions and comparing to soils supplemented with nitrogen and various carbon sources (mannose, casein, asparagine, coumaric acid). All data was compared to a previously available commercial assay. There were no significant differences in the maximum peak intensity or the time to peak response for all soils tested (p<0.001, alpha=0.05). The experimental assay plates can be reused on soils up to four times (based on a deviation of less than 5%), where the commercial assay should not be reused. The results indicate that the new oxygen-based bioassay is a cost effective, open source tool for functional profiling of microbial communities. PMID- 24211533 TI - The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. AB - The endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of interorganellar connections. The ER and mitochondria join together at multiple contact sites to form specific domains, termed mitochondria-ER associated membranes (MAMs), with distinct biochemical properties and a characteristic set of proteins. The functions of these two organelles are coordinated and executed at the ER-mitochondria interface, which provides a platform for the regulation of different processes. The roles played by the ER-mitochondria interface range from the coordination of calcium transfer to the regulation of mitochondrial fission and inflammasome formation as well as the provision of membranes for autophagy. The novel and unconventional processes that occur at the ER-mitochondria interface demonstrate its multifunctional and intrinsically dynamic nature. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components. PMID- 24211535 TI - IgG variable region and VH CDR3 diversity in unimmunized mice analyzed by massively parallel sequencing. AB - Most antigen-specific mouse antibodies have been derived by hybridoma technology, predominantly through use of the Balb/c strain. Much of the Balb/c germline repertoire of variable genes (V regions) is known. However, there is little information about the background expressed repertoire of IgG antibodies in mice, which reflects the baseline against which antigen-specific antibodies are generated through immunization. To assess this baseline repertoire, RNA was isolated from splenic B-cells enriched for expression of IgG from three mice. The RNA was individually amplified with three distinct PCR primer sets for comprehensive recovery of the heavy and light chain variable regions. Each PCR product was independently subjected to deep sequencing using 454 pyro-sequencing technology and analysed for redundancy, open reading frame, germline representation, and CDR3 sequence of the heavy chain variable region (VH CDR3) within and across the primer sets and mice. A highly skewed abundance of heavy and light chain variable gene usage was observed for all three primers in all three mice. While showing considerable overlap, there were differences among these profiles indicative of primer bias and animal-to-animal variation. VH CDR3 sequences were likewise highly skewed indicating that the heavy chain genes profiles substantially reflected individual antibodies. This observation was confirmed through analysis of randomly selected complete heavy chain variable sequences. However, there was very little redundancy in VH CDR3 sequences across the different mice. We conclude that the background IgG repertoire in young, unimmunized mice is highly skewed within individual mice and is diverse among them, a pattern similar to that observed in highly immunized mice. PMID- 24211534 TI - Identification and characterization of the related immune-enhancing proteins in crab Scylla paramamosain stimulated with rhubarb polysaccharides. AB - Recently, considerable interest has been focused on immunostimulants to reduce diseases in crab aquaculture. However, information regarding to the related immune-enhancing proteins in crabs is not available yet. In this study, rhubarb polysaccharides were tested for enhancement of the immune activity in crab Scylla paramamosain. Compared with those in the control group, values of, phenoloxidase (PO), alkaline phosphatase (AKP) and alkaline phosphatasein (ACP) activity in the, experimental group were improved significantly 4 d after the treatment. Furthermore, 15 and 17 altered proteins from haemocytes and hepatopancreas, respectively, were found in rhubarb polysaccharide-treated crabs using 2-DE approach. Of these, hemocyanin, chymotrypsin, cryptocyanin, C-type lectin receptor, and ferritin protein were identified by mass spectrometry. In addition, RT-PCR, analysis showed that the mRNA levels of hemocyanin and chymotrypsin increased about 2.4- and 1.4-fold in the experiment group. Moreover, the hemocyanin gene in S. paramamosain (SpHMC) was, cloned and characterized. SpHMC contains one open reading frame of 2022 bp and encodes a polypeptide of 673 amino acids. It is clustered into one branch along with crab hemocyanin in a phylogenetic tree. The mRNA transcripts of SpHMC were detected mainly in the tissues of, hepatopancreas, hemocyte and intestines, and its levels were up regulated significantly in hemocytes, of S. paramamosain treated with Vibrio parahemolyticus, Beta streptococcus or poly I:C for 6-48 h. Taken together, these studies found 5 related immune-enhancing proteins and a novel heomcyanin homologue with potential pathogen-resistant activities in crab. PMID- 24211538 TI - Integration of sensory information precedes the sensation of vection: a combined behavioral and event-related brain potential (ERP) study. AB - Illusory self-motion (known as vection) describes the sensation of ego-motion in the absence of physical movement. Vection typically occurs in stationary observers being exposed to visual information that suggest self-motion (e.g. simulators, virtual reality). In the present study, we tested whether sensory integration of visual information triggers vection: participants (N=13) perceived patterns of moving altered black-and-white vertical stripes on a screen that was divided into a central and a surrounding peripheral visual field. In both fields the pattern was either moving or stationary, resulting in four combinations of central and peripheral motions: (1) central and peripheral stripes moved into the same direction, (2) central and peripheral stripes moved in opposite directions, or (3) either the central or (4) the peripheral stripes were stable while the other stripes were in motion. This stimulation induced vection: Results showed significantly higher vection ratings when the stationary center of the pattern was surrounded by a moving periphery. Event-related potentials mirrored this finding: The occipital N2 was largest with stationary central and moving peripheral stripes. Our findings suggest that sensory integration of peripheral and central visual information triggers the perception of vection. Furthermore, we found evidence that neural processes precede the subjective perception of vection strength prior to the actual onset of vection. We will discuss our findings with respect to the role of stimulus eccentricity, stimulus' depth, and neural correlates involved during the genesis of vection. PMID- 24211536 TI - Centrosomal abnormalities characterize human and rodent cystic cholangiocytes and are associated with Cdc25A overexpression. AB - Hepatic cystogenesis in polycystic liver diseases is associated with abnormalities of cholangiocyte cilia. Given the crucial association between cilia and centrosomes, we tested the hypothesis that centrosomal defects occur in cystic cholangiocytes of rodents (Pkd2(WS25/-) mice and PCK rats) and of patients with polycystic liver diseases, contributing to disturbed ciliogenesis and cyst formation. We examined centrosomal cytoarchitecture in control and cystic cholangiocytes, the effects of centrosomal abnormalities on ciliogenesis, and the role of the cell-cycle regulator Cdc25A in centrosomal defects by depleting cholangiocytes of Cdc25A in vitro and in vivo and evaluating centrosome morphology, cell-cycle progression, proliferation, ciliogenesis, and cystogenesis. The cystic cholangiocytes had atypical centrosome positioning, supernumerary centrosomes, multipolar spindles, and extra cilia. Structurally aberrant cilia were present in cystic cholangiocytes during ciliogenesis. Depletion of Cdc25A resulted in i) a decreased number of centrosomes and multiciliated cholangiocytes, ii) an increased fraction of ciliated cholangiocytes with longer cilia, iii) a decreased proportion of cholangiocytes in G1/G0 and S phases of the cell cycle, iv) decreased cell proliferation, and v) reduced cyst growth in vitro and in vivo. Our data support the hypothesis that centrosomal abnormalities in cholangiocytes are associated with aberrant ciliogenesis and that accelerated cystogenesis is likely due to overexpression of Cdc25A, providing additional evidence that pharmacological targeting of Cdc25A has therapeutic potential in polycystic liver diseases. PMID- 24211537 TI - Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice. AB - Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression. PMID- 24211539 TI - An in vitro approach to assessing a potential drug interaction between MDMA (ecstasy) and caffeine. AB - 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug which causes long-term neurotoxicity and increased risk of fatality. In rats, MDMA toxicity is exacerbated by co-administration of caffeine. The aim of this study was to investigate whether caffeine altered the effects of MDMA in a battery of in vitro tests selected to model some of the known actions of MDMA in vivo. In cytotoxicity studies, caffeine modestly enhanced the effect of MDMA on neuronal N2a cell viability but not that of liver, intestinal or kidney cells. MDMA inhibited the formation of fluorescent metabolites by CYP2D6?CYP3A4>CYP1A2 but this was not altered by caffeine. Similarly, the inhibition of synaptosomal [(3)H] 5-HT uptake by MDMA was not affected by the presence of caffeine. Thus, these in vitro tests failed to detect any substantial interaction between caffeine and MDMA, highlighting the difficulty of modelling in vivo drug interactions using in vitro tests. However, the results show that the inhibition of synaptosomal [(3)H] 5-HT uptake by MDMA was greater at 41 degrees C and 25 degrees C than at 37 degrees C which raises the possibility that MDMA's effect on SERT in vivo may be increased as body temperature increases, contributing to its harmful effects in users. PMID- 24211540 TI - Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: role of glycine conjugates. AB - Excessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of SCRH (on day-1 after seeding) to various BAs for 24h, glycine-conjugated BAs were most potent in exerting toxicity. Moreover, unconjugated BAs showed significantly higher toxicity in day-1 compared to day-3 SCRH. When day-1/-3 SCRH were exposed (0.5 4h) to 5-100MUM (C)DCA, intracellular levels of unconjugated (C)DCA were similar, while intracellular levels of glycine conjugates were up to 4-fold lower in day-3 compared to day-1 SCRH. Sinusoidal efflux was by far the predominant efflux pathway of conjugated BAs both in day-1 and day-3 SCRH, while canalicular BA efflux showed substantial interbatch variability. After 4h exposure to (C)DCA, intracellular glycine conjugate levels were at least 10-fold higher than taurine conjugate levels. Taken together, reduced BA conjugate formation in day-3 SCRH results in lower intracellular glycine conjugate concentrations, explaining decreased toxicity of (C)DCA in day-3 versus day-1 SCRH. Our data provide for the first time a direct link between BA toxicity and glycine conjugate exposure in SCRH. PMID- 24211541 TI - Characterization of a murine type IIB procollagen-specific antibody. AB - Type II collagen is the major collagenous component of the cartilage extracellular matrix; formation of a covalently cross-linked type II collagen network provides cartilage with important tensile properties. The Col2a1 gene is encoded by 54 exons, of which exon 2 is subject to alternative splicing, resulting in different isoforms named IIA, IIB, IIC and IID. The two major procollagen protein isoforms are type IIA and type IIB procollagen. Type IIA procollagen mRNA contains exon 2 and is generated predominantly by chondroprogenitor cells and other non-cartilaginous tissues. Differentiated chondrocytes generate type IIB procollagen, devoid of exon 2. Although type IIA procollagen is produced in certain non-collagenous tissues during development, this developmentally-regulated alternative splicing switch to type IIB procollagen is restricted to cartilage cells. Though a much studied and characterized molecule, the importance of the various type II collagen protein isoforms in cartilage development and homeostasis is still not completely understood. Effective antibodies against specific epitopes of these isoforms can be useful tools to decipher function. However, most type II collagen antibodies to date recognize either all isoforms or the IIA procollagen isoform. To specifically identify the murine type IIB procollagen, we have generated a rabbit antibody (termed IIBN) directed to a peptide sequence that spans the murine exon 1-3 peptide junction. Characterization of the affinity-purified antibody by western blotting of collagens extracted from wild type murine cartilage or cartilage from Col2a1(+ex2) knock-in mice (which generates predominantly the type IIA procollagen isoform) demonstrated that the IIBN antibody is specific to the type IIB procollagen isoform. IIBN antibody was also able to detect the native type IIB procollagen in the hypertrophic chondrocytes of the wild type growth plate, but not in those of the Col2a1(+ex2) homozygous knock-in mice, by both immunofluorescence and immunohistochemical studies. Thus the IIBN antibody will permit an in-depth characterization of the distribution of IIB procollagen isoform in mouse skeletal tissues. In addition, this antibody will be an important reagent for characterizing mutant type II collagen phenotypes and for monitoring type II procollagen processing and trafficking. PMID- 24211542 TI - The quality of meat from sheep treated with tannin- and saponin-based remedies as a natural strategy for parasite control. AB - Lambs were assigned to four groups of seven and treated as follows for 12 days: control group (BP) was fed beet pulp; group T (tannin remedy) received the BP diet including 80 g/kg of quebracho extract; group S (saponin remedy) received the BP diet including 15 g/kg of quillaja extract; and group C had a free choice between T and S remedies. Lipid oxidation was lower in meat from S lambs compared to T lambs (P<0.05). Among the volatile compounds, lactate was lower in meat from S lambs compared to T animals (P=0.05). Metabolomic analysis showed that the T treatment increased ribose, fructose, glucose and sorbitol concentration in meat (P<0.05), while cholesterol was decreased by S and C treatments. The T treatment increased the concentration of C14:1 cis-9 (P<0.05). These findings indicate that treatments for parasite control containing tannins and saponins do not detrimentally affect sheep meat quality. PMID- 24211543 TI - Postmortem proteolysis in three muscles from growing and mature beef cattle. AB - The objective of this study was to determine calpain system activity and postmortem protein degradation in three muscles from growing (n=6, 7.3 +/- 0.5 months) and mature (n=6, 106.7 +/- 43.1 months) beef cattle. The ratio of MU calpain:total calpastatin activity tended to be lower in mature animals (P=0.08), suggesting reduced potential for proteolysis. Additionally, muscles from the mature group had greater calpastatin activity compared to calves at 6 days postmortem and had less MU-calpain autolysis and troponin-T and titin degradation during the aging period (P<0.01). Between the longissimus, semimembranosus, and triceps brachii muscles, the triceps brachii had the least postmortem proteolysis, with greater calpastatin activity and less troponin-T and titin degradation compared to other muscles (P<0.01). These data suggest that calpastatin activity in muscle from older animals is more persistent postmortem. This difference may contribute to the decreased protein degradation and increased toughness of beef from mature cattle, even after aging. PMID- 24211544 TI - Early on-line classification of beef carcasses based on ultimate pH by near infrared spectroscopy. AB - Prediction of ultimate pH (measured 48 h post mortem; pH(u)) in beef from Visible near infrared (VIS-NIR) spectra collected 20 to 40 min post mortem was assessed. Spectra were collected from carcasses (cows: n = 86, bulls: n = 170, steers: n = 363, and heifers: n = 38) in a commercial hot boning abattoir under routine conditions. Partial Least Squares (PLS) models showed limited accuracy with RMSE for validation equal to 0.26, 0.20 and 0.36 for the All-animals, Non-bulls and Bulls models, respectively. The pH(u)-PLS-predicted values were used to segregate carcasses as normal (pH(u)<5.8) or high (pH(u) >= 5.8) showing better performance, by correctly classifying at least 90% of high pH(u) carcasses. The Non-bulls model was equivalent to the current technology used in the abattoir to classify carcasses based on pH(u). Thus near infrared spectroscopy (NIRS) could be used for on-line classification of beef carcasses based on pH(u). PMID- 24211545 TI - Concentration of antioxidants in two muscles of mature dairy cows from Azores. AB - This study evaluated the concentrations of alpha-tocopherol, beta-carotene, creatine, carnosine, anserine and coenzyme Q10 in Longissimus dorsi (Ld) and Gluteus medius (Gm) muscles of culled dairy cows and the impact of age, production status before slaughter (dry-off vs lactating) and carcass weight on them. The effects of applying a finishing feeding regimen before slaughter were also examined. Gm muscle presented higher levels (P<0.001) of alpha-tocopherol (5.14 vs 3.61 MUg . g(-1)) beta-carotene (0.36 vs 0.27 MUg . g(-1)), anserine (59.24 vs 43.25 mg . 100 g(-1)) and coenzyme Q10 (3.33 vs 1.73 mg . 100 g(-1)), and by contrast lower (P<0.05) creatine concentration (502.40 vs 527.28 mg . 100 g(-1)) than Ld. Dry-off and lactating cows differed significantly in alpha tocopherol level (P<0.001) but not in the concentrations of the other compounds (P>0.05). The finishing feeding promoted higher mean concentrations of anserine and creatine but lower carnosine values (P>0.05) than directly slaughtered dry off cows. The variation between muscles and from animal-to-animal makes it difficult to exactly define the antioxidant status of the dairy cow's meat. PMID- 24211546 TI - Immunocastration improves carcass traits and beef color attributes in Nellore and Nellore*Aberdeen Angus crossbred animals finished in feedlot. AB - The objective was to examine the effects of immunocastration on carcass traits and meat quality of Nellore and Nellore*Aberdeen Angus male animals finished in feedlot. Surgically castrated, immunocastrated, and intact animals were finished in feedlot for 90 days. The animals were harvested, and carcass traits were evaluated. Carcasses were chilled, and one 2.5-cm steak was fabricated from Longissimus thoracis muscle. The steaks were individually vacuum packaged and frozen at -18 degrees C. Frozen steaks were thawed, and pH, instrumental color, cooking loss, and shear force were determined. Immunocastrated animals demonstrated greater (P<0.05) hot dressing percentage and cold dressing percentage than their surgically castrated counterparts. Furthermore, steaks from immunocastrated and surgically castrated animals exhibited greater redness (P<0.05) and lower darkness (P<0.05) than steaks from intact animals, indicating possible advantage in retailing. The results suggested that immunocastration may be utilized to improve carcass traits and beef color in feedlot-finished Nellore and Nellore*Aberdeen Angus males. PMID- 24211547 TI - Antimicrobial-coated polypropylene films with polyvinyl alcohol in packaging of fresh beef. AB - The utility of packaging films consisting of cast polypropylene/polyvinyl alcohol with rhubarb ethanolic extracts (REE) and cinnamon essential oil (CEO) in maintaining fresh beef quality was investigated. Fresh beefsteaks were packed with antimicrobial films containing different concentrations of REE and CEO. Beef characteristics, including pH, total viable counts, instrumentally measured color, weight loss, total volatile base nitrogen (TVB-N) and sensory quality were determined. All experimental films significantly inhibited bacterial growth (p<0.05) and maintained the pH and TVB-N of beefsteaks. Three of four experimental films significantly reduced instrumental color loss (p<0.05). Antimicrobial packaging films efficiently maintained the quality of fresh beefsteaks during storage. PMID- 24211548 TI - Chemical composition, vitamin E content, lipid oxidation, colour and cooking losses in meat from Tudanca bulls finished on semi-extensive or intensive systems and slaughtered at 12 or 14 months. AB - The effects of production system (SE: pasture based vs. IN: concentrate based) and slaughter age (12 vs. 14 months) on chemical composition, vitamin E and myoglobin contents, lipid oxidation at 0, 3 and 6 days of display, colour and cooking losses at 2 and 7 days postmortem from thirty-three Tudanca calves were studied. SE animals showed lower IMF and greater vitamin E contents (1.2 vs. 2.9% and 4.1 vs. 1.8 MUg/g, respectively). Thiobarbituric acid reactive substances (TBARS) increased (p <= 0.001) with display time and was greater in the IN system. After 6 days display, IN animals presented twofold TBARS values (1.4 vs. 0.8 mg malonaldehyde/kg meat). At 7 days postmortem, SE groups presented greater (p <= 0.05) L* and lower (p <= 0.05) b* and H degrees than IN groups. Myoglobin increased with age (3.4 to 3.9 mg/g meat), but differences (p <= 0.05) on a* and C* values were observed only between 12 and 14 months at 2 days postmortem. PMID- 24211549 TI - Proximate composition, antihypertensive and antioxidative properties of the semimembranosus muscle from pork and beef after cooking and in vitro digestion. AB - The aims of this study were to evaluate and compare proximate composition, antihypertensive activity and antioxidative capacity of the semimembranosus muscle from pork and beef and to study how these characteristics were affected by household preparation and subsequent digestion. The proximate composition was similar between pork and beef. Both pork and beef contained protein with the essential amino acids. Cooking in a heated pan did not affect the retention of lipid or sum of amino acids, but reduced the amount of the free amino acid taurine. The antihypertensive effect did not differ significantly between pork and beef, whereas the antioxidative capacity did. Cooking affected the antioxidative capacity negatively. The results from this study show that pork and beef are equally good sources of protein and bioactive properties, and whereas the nutritional composition is not affected, bioactive properties may be reduced after household preparations. PMID- 24211550 TI - A rapid low-cost high-density DNA-based multi-detection test for routine inspection of meat species. AB - The increasing occurrence of food frauds suggests that species identification should be part of food authentication. Current molecular-based species identification methods have their own limitations or drawbacks, such as relatively time-consuming experimental steps, expensive equipment and, in particular, these methods cannot identify mixed species in a single experiment. This project proposes an improved method involving PCR amplification of the COI gene and detection of species-specific sequences by hybridisation. Major innovative breakthrough lies in the detection of multiple species, including pork, beef, lamb, horse, cat, dog and mouse, from a mixed sample within a single experiment. The probes used are species-specific either in sole or mixed species samples. As little as 5 pg of DNA template in the PCR is detectable in the proposed method. By designing species-specific probes and adopting reverse dot blot hybridisation and flow-through hybridisation, a low-cost high-density DNA based multi-detection test suitable for routine inspection of meat species was developed. PMID- 24211551 TI - Glycerine levels in the diets of crossbred bulls finished in feedlot: carcass characteristics and meat quality. AB - The effects of corn replacement by different glycerine levels on carcass characteristics and meat quality of 40 young Puruna bulls, weighing 209 +/- 33.3 kg and 8 +/- 0.9 months old, finished in feedlot, were evaluated. The treatments were G00: without glycerine; G06: 6% glycerine; G12: 12% glycerine; and G18: 18% glycerine in the diets, on a DM basis. Hot weight, dressing, conformation and length carcass, leg length and cushion thickness were not (P>0.05) modified by different glycerine levels in the diets. Glycerine in the diets did not (P>0.05) affect fat thickness, Longissimus muscle area, marbling and texture. Muscle, fat and bone percentages were not (P>0.05) influenced by glycerine levels in the diets. No changes (P>0.05) in lightness (L*), redness (a*) and yellowness (b*) on LM occurred when glycerine was included at 0, 6, 12 or 18% in the diet. There was no (P>0.05) difference in LM moisture, ash, crude protein and total lipids when feeding different glycerine levels. The inclusion of glycerine decreased (P<0.01) total saturated (10.8%), and increased monounsaturated (7.4%) and poly unsaturated (44.0%) fatty acids, which resulted in a higher PUFA:SFA ratio (0.57). PMID- 24211552 TI - Nutritionally enhanced fermented sausages as a vehicle for potential probiotic lactobacilli delivery. AB - The suitability of three potential probiotic lactobacilli strains (Lactobacillus casei CTC1677, L. casei CTC1678 and Lactobacillus rhamnosus CTC1679), previously isolated from infants' faeces and characterized, and three commercial probiotic strains (Lactobacillus plantarum 299v, L. rhamnosus GG and L. casei Shirota) was assessed during the manufacture of low-acid fermented sausages (fuets) with reduced Na(+) and fat content. The inoculated strains were successfully monitored by RAPD-PCR during the process. L. rhamnosus CTC1679 was the only strain able to grow and dominate (levels ca. 10(8)CFU/g) the endogenous lactic acid bacteria population in two independent trials, throughout the ripening process. Thus, fuet containing L. rhamnosus CTC1679 as a starter culture could be a suitable vehicle for putative probiotic bacteria delivery. All the final products recorded a satisfactory overall sensory quality without any noticeable off-flavour, and with the characteristic sensory properties of low-acid fermented sausages. PMID- 24211553 TI - Including estimated intramuscular fat content from computed tomography images improves prediction accuracy of dry-cured ham composition. AB - In recent years, computed tomography (CT) has been proposed as a method for the non-destructive prediction of salt content, water content and water activity (aw) in dry-cured ham. However, fat produces an important disturbance in the predictions. The aim of this study was to determine the effect of including an intramuscular fat content (IMF) estimate in the predictive models on the model predictability and CT tube voltage requirements. CT tomograms were obtained at three voltages. IMF was estimated by image analysis of CT tomograms obtained at the lowest voltage. By including an IMF estimate in the model, the prediction error was reduced by more than half in the water and aw predictions, but had little effect on the salt prediction. Additionally, the amount of CT voltages required in the predictive model decreased from three to two for salt and aw predictions. PMID- 24211554 TI - Effective survival of immobilized Lactobacillus casei during ripening and heat treatment of probiotic dry-fermented sausages and investigation of the microbial dynamics. AB - The aim was the assessment of immobilized Lactobacillus casei ATCC 393 on wheat in the production of probiotic dry-fermented sausages and the investigation of the microbial dynamics. For comparison, sausages containing either free L. casei ATCC 393 or no starter culture were also prepared. During ripening, the numbers of lactobacilli exceeded 7 log cfu/g, while a drastic decrease was observed in enterobacteria, staphylococci and pseudomonas counts. Microbial diversity was further studied applying a PCR-DGGE protocol. Members of Lactobacillus, Leuconostoc, Lactococcus, Carnobacterium, Brochothrix, Bacillus and Debaryomyces were the main microbial populations detected. Microbiological and strain-specific multiplex PCR analysis confirmed that the levels of L. casei ATCC 393 in the samples after 66 days of ripening were above the minimum concentration for conferring a probiotic effect (>= 6 log cfu/g). However, after heat treatment, this strain was detected at the above levels, only in sausages containing immobilized cells. PMID- 24211555 TI - Influence of supplemental vitamin C on postmortem protein degradation and fatty acid profiles of the longissimus thoracis of steers fed varying concentrations of dietary sulfur. AB - The objective was to examine the effects of supplemental vitamin C (VC) on postmortem protein degradation and fatty acid profiles of cattle receiving varying concentrations of dietary sulfur (S). A longissimus muscle was collected from 120 Angus-cross steers assigned to a 3 * 2 factorial, evaluating three concentrations of dietary S (0.22, 0.34, and 0.55%) and two concentrations of supplemental VC (0 or 10 g h(-1)d(-1)). Increasing dietary S and VC supplementation (P<0.001) increased the percent polyunsaturated fatty acids of steaks. Addition of VC tended to increase (P = 0.09) both Fe and 2-thiobarbituric acid content of longissimus thoracis. Increasing S increased (P = 0.03) the proportion of 80-kDa subunit of MU-calpain. Addition of VC within the high S treatment increased (P = 0.05) the abundance of 76-kDa subunit of MU-calpain. Increasing S decreased troponin T degradation (P = 0.07) and protein carbonylation (P<0.01). Supplemental VC appears to alleviate negative effects of high S on autolysis of MU-calpain and protein degradation. PMID- 24211556 TI - Quantification of viable Escherichia coli O157:H7 in meat products by duplex real time PCR assays. AB - Rapid and specific detection of viable Escherichia coli O157:H7 cells in ready-to eat (RTE) meat products, by duplex quantitative PCR (qPCR) procedures with mRNA and SYBR Green and TaqMan methodologies were developed. Specific primers and probes were designed based on the serotype of E. coli O157:H7, fliCh7 and rfbE genes. No cross-reactivity with other microorganisms was observed. The detection limit of the assays was 10(1) or 10(2)CFU/g for artificially contaminated meat products, and after a 4h enrichment period at 37 degrees C, the detection limit decreased to about 1 CFU/g. Time-to completion of the assay was approximately 8h. Thus, these qPCR methods offer a useful, rapid and efficient tool for screening viable E. coli O157:H7 in RTE meat products. This tool could also be proposed for monitoring these foodborne pathogens in HACCP programs. PMID- 24211557 TI - Association of cyclists' age and sex with risk of involvement in a crash before and after adjustment for cycling exposure. AB - This study aimed to estimate the association of cyclists' age and sex with the risk of being involved in a crash with and without adjustment for their amount of exposure. We used the distribution of the entire population and cyclists (total and non-responsible) involved in road crashes in Spain between 1993 and 2009 held by the Spanish National Institute of Statistics and the Spanish General Traffic Directorate to calculate rates of exposure and involvement in a crash. Males aged 45-49 years were used as the reference category to obtain exposure rate ratios (ERR) and unadjusted crash rate ratios (URR). We then used these values in decomposition analysis to calculate crash rate ratios adjusted for exposure (ARR). The pattern of ARR was substantially different from URR. In both sexes the highest values were observed in the youngest age groups, and the values decreased as age increased except for a slight increase in the oldest age groups. In males, a slight increase in the lowest and highest age categories was observed for crashes resulting in severe injury or death, and a decrease was observed for the youngest cyclists who were wearing a helmet. The large differences between age and sex groups in the risk of involvement in a cycling crash are strongly dependent on differences in their exposure rates. Taking exposure rates into account, cyclists younger than 30 years and older than 65 years of age had the highest risk of being involved in a crash. PMID- 24211558 TI - Influences of pre-crash braking induced dummy - forward displacements on dummy behaviour during EuroNCAP frontal crashtest. AB - Combination of active and passive safety systems is a future key to further improvement in vehicle safety. Autonomous braking systems are able to reduce collision speeds, and therefore severity levels significantly. Passengers change their position due to pre-impact vehicle motion, a fact, which has not yet been considered in common crash tests. For this paper, finite elements simulations of crash tests were performed to show that forward displacements due to pre-crash braking do not necessarily increase dummy load levels. So the influence of different pre-crash scenarios, all leading to equal closing speeds in the crash phase, are considered in terms of vehicle motion (pitching, deceleration) and restraint system configurations (belt load limiter, pretensioner). The influence is evaluated by dummy loads as well as contact risk between the dummy and the interior. PMID- 24211559 TI - Low life jacket use among adult recreational boaters: a qualitative study of risk perception and behavior factors. AB - BACKGROUND: Life jackets may prevent one in two drowning deaths, however, 85% of recreational boating-related drowning victims in the United States in 2012 did not wear a life jacket. This study explored behavioral factors and strategies to encourage consistent life jacket use among adult recreational boaters. METHODS: We conducted a qualitative study among boat owners who boat regularly, and explored factors associated with life jacket use by adults and child or adolescent passengers. Sixteen boaters participated in four focus groups. RESULTS: Most boaters reported inconsistent use of life jackets, using them only when conditions were poor. Each described episodes of unpredictable boating risk which occurred despite favorable conditions. Most required younger child passengers to wear a life jacket, but reported resistance among older children. Barriers to consistent life jacket use included discomfort and the belief that life jacket use indicated inexperience or poor swimming ability. Participants stated that laws requiring life jacket use would change behavior especially for children. The only demonstrated behavior change among group members was associated with use of inflatable life jacket devices. CONCLUSIONS: Boating risk is inherently unpredictable; therefore interventions should focus on strategies for increasing consistent use of life jackets. Passage and enforcement of life jacket legislation for older children and adults is likely a promising approach for behavior change. Designing more comfortable, better-fitting, more appealing life jackets will be paramount to encouraging consistent use. PMID- 24211560 TI - Concealing their communication: exploring psychosocial predictors of young drivers' intentions and engagement in concealed texting. AB - Making a conscious effort to hide the fact that you are texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted away from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened risk of crashing from engaging in this behaviour. This study investigated the phenomenon of concealed texting while driving, and utilised an extended Theory of Planned Behaviour (TPB) including the additional predictors of moral norm, mobile phone involvement, and anticipated regret to predict young drivers' intentions and subsequent behaviour. Participants (n=171) were aged 17-25 years, owned a mobile phone, and had a current driver's licence. Participants completed a questionnaire measuring their intention to conceal texting while driving, and a follow-up questionnaire a week later to report their behavioural engagement. The results of hierarchical multiple regression analyses showed overall support for the predictive utility of the TPB with the standard constructs accounting for 69% of variance in drivers' intentions, and the extended predictors contributing an additional 6% of variance in intentions over and above the standard constructs. Attitude, subjective norm, PBC, moral norm, and mobile phone involvement emerged as significant predictors of intentions; and intention was the only significant predictor of drivers' self-reported behaviour. These constructs can provide insight into key focal points for countermeasures including advertising and other public education strategies aimed at influencing young drivers to reconsider their engagement in this risky behaviour. PMID- 24211561 TI - Crash reconstruction and crash modification factors. AB - This paper addresses the following question: Under what conditions can reconstructed road crashes be used to estimate the effect of a safety-related countermeasure? Results developed by Pearl and his associates are used to draw two main conclusions. First, when one can (1) identify a structural equation describing a type of crash, (2) identify an additional structural equation describing the countermeasure's impact, and (3) estimate the initiating conditions for a set of reconstructed crashes, then a lower bound for a crash modification factor can be estimated by simulating whether or not each of the reconstructed crashes would still have occurred had the countermeasure been present. If the countermeasure's effect is monotonic this bound becomes tight. Second, in situations where it is not possible to reliably identify the structural equations needed for simulation, but where one can (1) identify a set of crash inputs which, when given, make the crash outcome conditionally independent of the countermeasure, and (2) predict how the distribution of these inputs will change in response to the countermeasure, then nonparametric estimation of the countermeasure's crash modification factor is possible. When it is not possible to predict the countermeasure's effect on the conditioning variables it may still be possible to identify constraints or specifications which the countermeasure should satisfy in order to realize a target crash modification. PMID- 24211562 TI - Forgivingness, anger, and hostility in aggressive driving. AB - This study was aimed at investigating the relationship between trait forgivingness, general anger, hostility, driving anger, and self-reported aggressive driving committed by the driver him/herself ("self" scale) and perceiving him/herself as an object of other drivers' aggressive acts ("other" scale). The Slovak version of questionnaires was administrated to a sample of 612 Slovak and Czech drivers. First, the factor structure of the Driver Anger Indicators Scale (DAIS) was investigated. Factor analyses of the self and other parts of the DAIS resulted in two factors, which were named as aggressive warnings and hostile aggression and revenge. Next, the results showed that from all dependent variables (scales of the DAIS), self-reported aggressive warnings (self) on the road were predicted best by chosen person-related factors. The path model for aggressive warnings (self) suggested that trait forgivingness and general anger were fully mediated by driving anger whereas hostility proved to be a unique predictor of aggressive behavior in traffic. Driving anger was found to be the best predictor of perceptions that other drivers behave aggressively. PMID- 24211563 TI - In vivo estimation of pigment composition and optical absorption cross-section by spectroradiometry in four aquatic photosynthetic micro-organisms. AB - The objective of the present study was to estimate in vivo pigment composition and to retrieve absorption cross-section values, a(*), of photosynthetic micro organisms using a non-invasive technique of reflectance spectrometry. To test the methodology, organisms from different taxonomical groups and different pigment composition were used (Spirulina platensis a Cyanophyta, Porphyridium cruentum a Rhodophyta, Dunaliella tertiolecta a Chlorophyta and Entomoneis paludosa a Bacillariophyta) and photoacclimated to two different irradiance levels: 25 MUmol photonm(-2)s(-1) (Low Light, LL) and 500 MUmol photonm(-2)s(-1) (High Light, HL). Second derivative spectra from reflectance were used to identify pigment in vivo absorption bands that were linked to specific pigments detected by high performance liquid chromatography. Whereas some absorption bands such as those induced by Chlorophyll (Chl) a (416, 440, 625 and around 675 nm) were ubiquous, others were taxonomically specific (e.g. 636 nm for Chl c in E. paludosa) and/or photo-physiological dependent (e.g. 489 nm for zeaxanthin in the HL-acclimated S. platensis). The optical absorption cross-section, a(*), was retrieved from reflectance data using a radiative transfer model previously developed for microphytobenthos. Despite the cellular Chl a decrease observed from LL to HL (up to 88% for S. platensis), the a(*) increased, except for P. cruentum. This was attributed to a 'package effect' and to a greater absorption by photoprotective carotenoids that did not contribute to the energy transfer to the core Chl a. PMID- 24211564 TI - Forming social capital--does participatory planning foster trust in institutions? AB - Participatory planning that includes interest groups and municipal representatives has been presented as a means to deal with the increasing difficulty to reach arrangements due to progressively scarce land resources. Under dispute is whether collaborative forms of planning augment social capital or whether they might actually cause the destruction of such a valuable social commodity. In this paper we focus on trust in institution as a specific dimension of social capital because we argue that this is one of the effects the convenors of such participatory planning procedures are most interested in. We pursue a pre post design and survey advisory group members of five on-going river-related planning processes in Switzerland. Controlling for generalised trust, we investigate how trust in institutions is affected over time by the quality of such processes and the degree of participation they offer. We find that generalised trust is highly correlated with initial levels of trust and so is process quality. Particularly the latter finding challenges the usually assumed direction of causality according to which process quality influences trust building. Additionally, we find a positive (non-significant) effect of process quality on changes in trust, while a higher degree of participation rather seems to hinder trust building. We suppose this indicates that under the conditions of limited time and resources more attention should be paid to how to improve the quality of participatory processes than putting much effort in increasing the degree of participation. PMID- 24211565 TI - Enhanced removal of nitrate from water using surface modification of adsorbents- a review. AB - Elevated concentration of nitrate results in eutrophication of natural water bodies affecting the aquatic environment and reduces the quality of drinking water. This in turn causes harm to people's health, especially that of infants and livestock. Adsorbents with the high capacity to selectively adsorb nitrate are required to effectively remove nitrate from water. Surface modifications of adsorbents have been reported to enhance their adsorption of nitrate. The major techniques of surface modification are: protonation, impregnation of metals and metal oxides, grafting of amine groups, organic compounds including surfactant coating of aluminosilicate minerals, and heat treatment. This paper reviews current information on these techniques, compares the enhanced nitrate adsorption capacities achieved by the modifications, and the mechanisms of adsorption, and presents advantages and drawbacks of the techniques. Most studies on this subject have been conducted in batch experiments. These studies need to include continuous mode column trials which have more relevance to real operating systems and pilot-plant trials. Reusability of adsorbents is important for economic reasons and practical treatment applications. However, only limited information is available on the regeneration of surface modified adsorbents. PMID- 24211566 TI - Removal of Pb2+ using a biochar-alginate capsule in aqueous solution and capsule regeneration. AB - A biochar-alginate capsule (BAC) was successfully synthesized by dropping a mixture solution of biochar (BC) and calcium chloride (CaCl2) into an alginate (AG) solution, with adjusting the mass ratio of BC to AG. The adsorption characteristics of the BAC were investigated by measuring the removal of lead ions (Pb(2+)) from an aqueous solution. The maximum adsorption of Pb(2+) was found at a pH of 5.0 and an adsorption time of 120 min. The lead adsorption equilibrium data of the BAC fit well with the Langmuir and Freundlich equations. Based on the Langmuir isotherm, which was a better fit than the Freundlich isotherm, the maximum sorption capacity of Pb(2+) by BAC (BC:AG = 8:1) was 263.158 mg/g, which is much higher than the capacity for other adsorbents. The sorption adequately followed the pseudo second-order kinetic expression (R(2) = 0.997). The BAC was easily collected after the Pb(2+) adsorption process and highly recoverable (90-95%) using a HNO3 solution. The adsorption efficiency of Pb(2+) by the recovered BAC remained around 70% of the initial adsorption capacity even after being recycled 10 times (repeated adsorption-desorption). PMID- 24211567 TI - Comparison of risk-based decision-support systems for brownfield site rehabilitation: DESYRE and SADA applied to a Romanian case study. AB - Brownfield rehabilitation is an essential step for sustainable land-use planning and management in the European Union. In brownfield regeneration processes, the legacy contamination plays a significant role, firstly because of the persistent contaminants in soil or groundwater which extends the existing hazards and risks well into the future; and secondly, problems from historical contamination are often more difficult to manage than contamination caused by new activities. Due to the complexity associated with the management of brownfield site rehabilitation, Decision Support Systems (DSSs) have been developed to support problem holders and stakeholders in the decision-making process encompassing all phases of the rehabilitation. This paper presents a comparative study between two DSSs, namely SADA (Spatial Analysis and Decision Assistance) and DESYRE (Decision Support System for the Requalification of Contaminated Sites), with the main objective of showing the benefits of using DSSs to introduce and process data and then to disseminate results to different stakeholders involved in the decision making process. For this purpose, a former car manufacturing plant located in the Brasov area, Central Romania, contaminated chiefly by heavy metals and total petroleum hydrocarbons, has been selected as a case study to apply the two examined DSSs. Major results presented here concern the analysis of the functionalities of the two DSSs in order to identify similarities, differences and complementarities and, thus, to provide an indication of the most suitable integration options. PMID- 24211568 TI - Keeping wetlands wet in the western United States: adaptations to drought in agriculture-dominated human-natural systems. AB - Water is critical to protecting wetlands in arid regions, especially in agriculture-dominated watersheds. This comparative case study analyzes three federal wildlife refuges in the Bear River Basin of the U.S. West where refuge managers secured water supplies by adapting to their local environmental context and their refuge's relationship to agriculture in being either irrigation dependent, reservoir-adjacent or diked-delta wetlands. We found that each refuge's position confers different opportunities for securing a water supply and entails unique management challenges linked to agricultural water uses. Acquiring contextually-appropriate water rights portfolios was important for protecting these arid region wetlands and was accomplished through various strategies. Once acquired, water is managed to buffer wetlands against fluctuations caused by a dynamic climate and agricultural demands, especially during droughts. Management plans are responsive to needs of neighboring water users and values of the public at large. Such context-specific adaptations will be critical as the West faces climate change and population growth that threaten wetlands and agricultural systems to which they are linked. PMID- 24211569 TI - Biological removal of phyto-sterols in pulp mill effluents. AB - Phyto-sterols and extractives found in pulp mill effluents are suspected to cause endocrine abnormalities in receiving water fish. The control of sterols in pulp mill effluents through biological secondary wastewater treatment was studied using two lab-scale bioreactor systems. After achieving a stable performance, both bioreactor systems successfully removed (>90%) sterols and the estimated biodegradation was up to 80%. Reactor 1 system operating at 6.7 +/- 0.2 pH effectively treated pulp mill effluent sterols spiked up to 4500 MUg/L in 11 h HRT and 11 day SRT. However, Reactor 2 system operating at 7.6 +/- 0.2 pH performed relatively poorly. Retention time reductions beyond critical values deteriorated the performance of treatment systems and quickly reduced the sterols biodegradation. The biodegradation loss was indicated by mixed liquor sterols content that started increasing. This biodegradation loss was compensated by the increased role of bio-adsorption and the overall sterols removal remained relatively high. Hence, a relatively small (20-30%) loss in the overall sterols removal efficiency did not fully reflect the associated major (60-70%) loss in the sterols biodegradation because the amount of sterols accumulated in the sludge due to adsorption increased so the estimate of sterols removal through adsorption increased from 30-40% to 70-80% keeping the overall sterols removal still high. PMID- 24211570 TI - The disappearing Environmental Kuznets Curve: a study of water quality in the Lower Mekong Basin (LMB). AB - The literature is flush with articles focused on estimating the Environmental Kuznets Curve (EKC) for various pollutants and various locations. Most studies have utilized air pollution variables; far fewer have utilized water quality variables, all with mixed results. We suspect that mixed evidence of the EKC stems from model and error specification. We analyze annual data for four water quality indicators, three of them previously unstudied - total phosphorus (TOTP), dissolved oxygen (DO), ammonium (NH4) and nitrites (NO2) - from the Lower Mekong Basin region to determine whether an Environmental Kuznets Curve (EKC) is evident for a transboundary river in a developing country and whether that curve is dependent on model specification and/or pollutant. We build upon previous studies by correcting for the problems of heteroskedasticity, serial correlation and cross-sectional dependence. Unlike multi-country EKC studies, we mitigate for potential distortion from pooling data across geographically heterogeneous locations by analyzing data drawn from proximate locations within a specific international river basin in Southeast Asia. We also attempt to identify vital socioeconomic determinants of water pollution by including a broad list of explanatory variables alongside the income term. Finally, we attempt to shed light on the pollution-income relationship as it pertains to trans-boundary water pollution by examining data from an international river system. We do not find consistent evidence of an EKC for any of the 4 pollutant indicators in this study, but find the results are entirely dependent on model and error specification as well as pollutant. PMID- 24211571 TI - Impact of DNA methyltransferases on the epigenetic regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in malignant melanoma. AB - Aberrant promoter methylation and resultant silencing of TRAIL decoy receptors were reported in a variety of cancers, but to date little is known about the relevance of this epigenetic modification in melanoma. In this study, we examined the methylation and the expression status of TRAIL receptor genes in cutaneous and uveal melanoma cell lines and specimens and their interaction with DNA methyltransferases (DNMTs) DNMT1, DNMT3a, and DNMT3b. DR4 and DR5 methylation was not frequent in cutaneous melanoma but on the contrary it was very frequent in uveal melanoma. No correlation between methylation status of DR4 and DR5 and gene expression was found. DcR1 and DcR2 were hypermethylated with very high frequency in both cutaneous and uveal melanoma. The concordance between methylation and loss of gene expression ranged from 91% to 97%. Here we showed that DNMT1 was crucial for DcR2 hypermethylation and that DNMT1 and DNMT3a coregulate the methylation status of DcR1. Our work also revealed the critical relevance of DcR1 and DcR2 expression in cell growth and apoptosis either in cutaneous or uveal melanoma. In conclusion, the results presented here claim for a relevant impact of aberrant methylation of decoy receptors in melanoma and allow to understand how the silencing of DcR1 and DcR2 is related to melanomagenesis. PMID- 24211572 TI - Redox states of Desulfovibrio vulgaris DsrC, a key protein in dissimilatory sulfite reduction. AB - Dissimilatory reduction of sulfite is carried out by the siroheme enzyme DsrAB, with the involvement of the protein DsrC, which has two conserved redox-active cysteines. DsrC was initially believed to be a third subunit of DsrAB. Here, we report a study of the distribution of DsrC in cell extracts to show that, in the model sulfate reducer Desulfovibrio vulgaris, the majority of DsrC is not associated with DsrAB and is thus free to interact with other proteins. In addition, we developed a cysteine-labelling gel-shift assay to monitor the DsrC redox state and behaviour, and procedures to produce the different redox forms. The oxidized state of DsrC with an intramolecular disulfide bond, which is proposed to be a key metabolic intermediate, could be successfully produced for the first time by treatment with arginine. PMID- 24211573 TI - Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading. AB - Cardiac hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Prevention or regression of cardiac hypertrophy can be a major therapeutic target. Although regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified. In the present study, we investigated the role of autophagy in regression of cardiac hypertrophy. Wild type mice showed cardiac hypertrophy after continuous infusion of angiotensin II for 14 days using osmotic minipumps, and regression of cardiac hypertrophy was observed 7 days after removal of the minipumps. Autophagy was induced during regression of cardiac hypertrophy, as evidenced by an increase in microtubule associated protein 1 light chain 3 (LC3)-II protein level. Then, we subjected cardiac-specific Atg5-deficient (CKO) and control mice (CTL) to angiotensin II infusion for 14 days. CKO and CTL developed cardiac hypertrophy to a similar degree without contractile dysfunction. Seven days after removal of the minipumps, CKO showed significantly less regression of cardiac hypertrophy compared with CTL. Regression of pressure overload-induced cardiac hypertrophy after unloading was also attenuated in CKO. These results suggest that autophagy is necessary for regression of cardiac hypertrophy during unloading of neurohumoral and hemodynamic stress. PMID- 24211574 TI - CRISPR/Cas-induced double-strand breaks boost the frequency of gene replacements for humanizing the mouse Cnr2 gene. AB - The CRISPR/Cas technology has been successfully used to stimulate the integration of small DNA sequences in a target locus to produce gene mutations. However, many applications require homologous recombination using large gene-targeting constructs. Here we address the potential of CRISPR/Cas-mediated double-strand breaks to enhance the genetic engineering of large target sequences using a construct for "humanizing" the mouse Cnr2 gene locus. We designed a small-guide RNA that directs the induction of double strand breaks by Cas9 in the Cnr2 coding exon. By co-transfection of the CRISPR/Cas system with the 10 kb targeting construct we were able to boost the recombination frequency more than 200-fold from 0.27% to 67%. This simple technology can thus be used for the homologous integration of large gene fragments and should greatly enhance our ability to generate any kind of genetically altered mouse models. PMID- 24211575 TI - SIRT1 negatively regulates the protein stability of HIPK2. AB - In the present study, we investigated whether a histone deacetylase sirtuin 1 (SIRT1) can regulate the protein stability of homeodomain-interacting protein kinase 2 (HIPK2). We observed the evidence of molecular interaction between SIRT1 and HIPK2. Interestingly, overexpression or pharmacological activation of SIRT1 promoted ubiquitination and the proteasomal degradation of HIPK2 whereas inhibition of SIRT1 activity increased the protein level of HIPK2. Furthermore, a SIRT1 activator decreased the level of HIPK2 acetylation whereas an inhibitor increased the acetylation level. These results suggest that SIRT1 may deacetylate and promote the ubiquitination and subsequent proteasomal degradation of HIPK2. PMID- 24211576 TI - Ribosomal protein S3 is secreted as a homodimer in cancer cells. AB - Protein secretion is a general phenomenon by which cells communicate with the extracellular environment. Secretory proteins, including hormones, enzymes, toxins, and antimicrobial peptides have various functions in extracellular environments. Here, we determined that ribosomal protein S3 (rpS3) is homodimerized and secreted in several cancer cell lines such as HT1080 (human fibrosarcoma) and MPC11 (mouse plasmacytoma). Moreover, we found that the secreted rpS3 protein increased in doxorubicin-resistant MPC11 cells compared to that in MPC11 cells. In addition, we also detected that the level of secreted rpS3 increased in more malignant cells, which were established with continuous exposure of cigarette smoke condensate. These findings suggest that the secreted rpS3 protein is an indicator of malignant tumors. PMID- 24211577 TI - Crystal structure of Cas1 from Archaeoglobus fulgidus and characterization of its nucleolytic activity. AB - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR associated (Cas) proteins are involved in bacterial acquired immunity against incoming hazardous genetic materials. Cas1 is ubiquitous in CRISPR-containing microorganisms and supposed to recognize and cleave a foreign nucleic acid, and integrate the cleaved fragment into host genome using a yet unidentified mechanism. However, all the reported Cas1s did not show the nucleolytic activity, which makes its role still obscure. The elucidated crystal structure of Cas1 from Archaeoglobus fulgidus (AfCas1) shows a butterfly-like dimeric structure. The Asp out of three confirmed nucleolytic residues of Glu, His, and Asp in other Cas1s is replaced with Glu in AfCas1. Further, insertion of five residues into one of two loops, which are close to the catalytic center of and disordered in other Cas1 structures, partially covers the active site of AfCas1. Nonetheless, in vitro assays show that its nucleic acid-binding activity was not impaired against the tested single-stranded (ss) DNA, various forms of double-stranded (ds) DNA, or ssRNA with a hydrolyzing activity against ssRNA and dsDNA in a metal ion dependent way. These results support the proposed Cas1's function at the early step of this bacterial immune system. PMID- 24211578 TI - Retina-specific gene excision by targeted expression of Cre recombinase. AB - The use of Cre recombinase for conditional targeting permits the controlled removal or activation of genes in specific tissues and at specific times of development. The Rho-Cre mice provide an improved tool for studying gene ablation in rod photoreceptor cells. To establish a robust expression of Rho-Cre transgenic mice that would be useful for the study of various protein functions in photoreceptor cells, a total 11,987 kb fragment (pNCHS4 Rho-NLS-cre) containing human rhodopsin promoter was cloned. The Rho-Cre plasmid was digested with EcoR1 and I Ceu-1, and the 9.316 kb fragment containing the hRho promoter and Cre recombinase gel was purified. To generate transgenic mice, the purified DNA fragment was injected into fertilized oocytes according to standard protocols. ROSA26R reported the steady expression of Rho-Cre especially in photoreceptor cells, allowing further excising proteins in rod photoreceptors across the retina. This Rho-Cre transgenic line should thus prove useful as a general deletor line for genetic analysis of diverse aspects of retinopathy. PMID- 24211579 TI - Characterization of a dwarf mutant allele of Arabidopsis MDR-like ABC transporter AtPGP1 gene. AB - Asymmetric auxin distribution caused by polar auxin transport (PAT) regulates many plant developmental and physiological processes. Plant two closely ABC (ATP binding cassette) transporter, AtPGP1 and AtPGP19 (AtMDR1), have been implicated in auxin transport. However, unlike atpgp19 mutant and atpgp1 atmdr1 double mutant show decreased apical dominance, reduced growth, and impaired basipetal auxin transport, atpgp1 mutant exhibit no significant difference from wild type. We report a new allele of atpgp1 mutants, designated as atpgp1-2, which showed shorter hypocotyl and dwarf phenotype under long-day condition. Auxin transport activity was greatly impaired and NPA-sensitivity was decreased in the mutant. Moreover, we detected transcript in the atpgp1 mutants reported previously, but not in atpgp1-2. These results suggest a direct involvement of AtPGP1 in auxin transport processes controlling plant growth. PMID- 24211580 TI - Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint. AB - Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy. PMID- 24211581 TI - The interplay between epigenetic silencing, oncogenic KRas and HIF-1 regulatory pathways in control of BNIP3 expression in human colorectal cancer cells. AB - Bcl-2/adenovirus E1B-19kDa-interacting protein 3 (BNIP3) is an important mediator of cell survival and a member of the Bcl-2 family of proteins that regulate programmed cell death and autophagy. We have previously established a link between the expression of oncogenic HRas and up-regulation of BNIP3 and the control of autophagy in cancer cells. However, in view of varied expression of BNIP3 in different tumor types and emerging uncertainties as to the role of epigenetic silencing, oncogenic regulation and the role of BNIP3 in cancer are still poorly understood. In the present study we describe profound effect of KRas on the expression of methylated BNIP3 in colorectal cancer cells and explore the interplay between HIF-1, hypoxia pathway and oncogenic KRas in this context. We observed that BNIP3 mRNA remains undetectable in aggressive DLD-1 cells harboring G13D mutant KRAS and HT-29 colorectal cancer cells unless the cells are exposed to demethylating agents such as 5-aza-2'-deoxycytidine. Following this treatment BNIP3 expression remains uniquely dependent on the Ras activity. We found that hypoxia or pharmacological activation of HIF-1 alone contributes to, but is not sufficient for efficient induction of BNIP3 mRNA transcription in cells lacking mutant KRas activity. The up-regulation of BNIP3 by KRas in this setting is mediated by the MAPK pathway, and is attenuated by the respective inhibitors (PD98059, U0126). Thus, we demonstrate the novel mechanism where activity of Ras is essential for 5-aza-2'-deoxycytidine-mediated BNIP3 expression. Moreover, we found that 5-aza-2'-deoxycytidine-mediated or enforced up-regulation of BNIP3 in DLD-1 cells results in KRas-dependent resistance to 5-Fluorouracil. PMID- 24211582 TI - Ubiquitin E3 ligase SCF(beta-TRCP) regulates TRIB2 stability in liver cancer cells. AB - Tribbles homolog 2 (TRIB2) is functionally important for liver cancer cell survival and transformation. Our previous study demonstrates TRIB2 is stable in liver cancer cells due to the impaired ubiquitination by Smurf1. However, overexpression of Smurf1 alone cannot completely abolish TRIB2 protein expression, whether other potential factors involved in the degradation of TRIB2 still remains unclear. In the present study, we reveal that the stability and ubiquitination of TRIB2 can also be controlled by ubiquitin E3 ligase SCF(beta TRCP). Depletion of either Cullin1 or beta-TRCP up-regulates TRIB2 protein expression. Moreover, knockdown of beta-TRCP extends the half-life, whereas reduces ubiquitylation of TRIB2. Similar to Smurf1, beta-TRCP exerts its role through the TRIB2 Degradation Domain (TDD) at the N-terminus of the TRIB2 protein. Hence, we add TRIB2 to the substrate list of SCF(beta-TRCP) and the finding may be helpful in the treatment of TRIB2 dependent liver cancer. PMID- 24211583 TI - Big angiotensin-25: a novel glycosylated angiotensin-related peptide isolated from human urine. AB - The renin-angiotensin system (RAS), including angiotensin II (Ang II), plays an important role in the regulation of blood pressure and body fluid balance. Consequently, the RAS has emerged as a key target for treatment of kidney and cardiovascular disease. In a search for bioactive peptides using an antibody against the N-terminal portion of Ang II, we identified and characterized a novel angiotensin-related peptide from human urine as a major molecular form. We named the peptide Big angiotensin-25 (Bang-25) because it consists of 25 amino acids with a glycosyl chain and added cysteine. Bang-25 is rapidly cleaved by chymase to Ang II, but is resistant to cleavage by renin. The peptide is abundant in human urine and is present in a wide range of organs and tissues. In particular, immunostaining of Bang-25 in the kidney is specifically localized to podocytes. Although the physiological function of Bang-25 remains uncertain, our findings suggest it is processed from angiotensinogen and may represent an alternative, renin-independent path for Ang II synthesis in tissue. PMID- 24211584 TI - Fenofibrate, a peroxisome proliferator-activated receptor alpha ligand, prevents abnormal liver function induced by a fasting-refeeding process. AB - Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist, is an anti-hyperlipidemic agent that has been widely used in the treatment of dyslipidemia. In this study, we examined the effect of fenofibrate on liver damage caused by refeeding a high-fat diet (HFD) in mice after 24h fasting. Here, we showed that refeeding HFD after fasting causes liver damage in mice determined by liver morphology and liver cell death. A detailed analysis revealed that hepatic lipid droplet formation is enhanced and triglyceride levels in liver are increased by refeeding HFD after starvation for 24h. Also, NF-kappaB is activated and consequently induces the expression of TNF-alpha, IL1-beta, COX 2, and NOS2. However, treating with fenofibrate attenuates the liver damage and triglyceride accumulation caused by the fasting-refeeding HFD process. Fenofibrate reduces the expression of NF-kappaB target genes but induces genes for peroxisomal fatty acid oxidation, peroxisome biogenesis and mitochondrial fatty acid oxidation. These results strongly suggest that the treatment of fenofibrate ameliorates the liver damage induced by fasting-refeeding HFD, possibly through the activation of fatty acid oxidation. PMID- 24211585 TI - FERM domain promotes resveratrol-induced apoptosis in endothelial cells via inhibition of NO production. AB - Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 MUM resveratrol, whereas FERM had no effect on apoptosis induced by TNF-alpha. We determined that resveratrol at low doses (<20 MUM) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production. PMID- 24211586 TI - The UbL protein UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. AB - UBTD1 is a previously uncharacterized ubiquitin-like (UbL) domain containing protein with high homology to the mitochondrial Dc-UbP/UBTD2 protein. Here we show that UBTD1 and UBTD2 belong to a family of proteins that is conserved through evolution and found in metazoa, funghi, and plants. To gain further insight into the function of UBTD1, we screened for interacting proteins. In a yeast-2-hybrid (Y2H) screen, we identified several proteins involved in the ubiquitylation pathway, including the UBE2D family of E2 ubiquitin conjugating enzymes. An affinity capture screen for UBTD1 interacting proteins in whole cell extracts also identified members of the UBE2D family. Biochemical characterization of recombinant UBTD1 and UBE2D demonstrated that the two proteins form a stable, stoichiometric complex that can be purified to near homogeneity. We discuss the implications of these findings in light of the ubiquitin proteasome system (UPS). PMID- 24211587 TI - Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain. AB - Neural stem cells continuously generate new neurons in the ventricular subventricular zone (V-SVZ) of the postnatal and adult mammalian brain. New neurons born in the rodent V-SVZ migrate toward the olfactory bulb (OB), where they differentiate into interneurons. To reveal novel intracellular molecular mechanisms that control postnatal neuronal migration, we performed a global proteomic search for proteins interacting with Girdin, an essential protein for postnatal neuronal migration. Using GST pull-down and LC-MS/MS shotgun analysis, we identified cytoskeletal proteins, cytoskeleton-binding proteins, and signal transduction proteins as possible participants in neuronal migration. Our results suggest that Girdin and Girdin-interacting proteins control neuronal migration by regulating actin and/or microtubule dynamics. PMID- 24211588 TI - Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT(2B) receptor and the ERK1/2 signalling pathway. AB - Interleukin-6 (IL-6) is a potent stimulator of osteoclastic bone resorption. Osteocyte secretion of IL-6 plays an important role in bone metabolism. Serotonin (5-HT) has recently been reported to regulate bone metabolism. The aim of this study was to evaluate the effect of serotonin on osteocyte expression of IL-6. The requirement for the 5-HT receptor(s) and the role of the extracellular signal regulated kinase 1/2 (ERK1/2) in serotonin-induced IL-6 synthesis were examined. In this study, real-time PCR and ELISA were used to analyse IL-6 gene and protein expression in serotonin-stimulated MLO-Y4 cells. ERK1/2 pathway activation was determined by Western blot. We found that serotonin significantly activated the ERK1/2 pathway and induced IL-6 mRNA expression and protein synthesis in cultured MLO-Y4 cells. However, these effects were abolished by pre-treatment of MLO-Y4 cells with a 5-HT2B receptor antagonist, RS127445 or the ERK1/2 inhibitor, PD98059. Our results indicate that serotonin stimulates osteocyte secretion of IL 6 and that this effect is associated with activation of 5-HT2B receptor and the ERK1/2 pathway. These findings provide support for a role of serotonin in bone metabolism by indicating serotonin regulates bone remodelling by mediating an inflammatory cytokine. PMID- 24211590 TI - Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy. AB - Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 degrees C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. PMID- 24211589 TI - Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts. AB - Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, the activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1 SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis. PMID- 24211591 TI - Novel analgesic peptides from the tree frog of Hyla japonica. AB - Two novel analgesic peptides (Analgesin-HJ, FWPVI-NH2 and Analgesin-HJ(I5T), FWPVT-NH2) were identified from the skin of the tree frog, Hyla japonica. There are 171 amino acid residues in the precursor encoding analgesin-HJs. The precursor contains 10 copies of mature peptide, which include 9 copies of analgesin-HJ and one copy of analgesin-HJ(I5T). Results from analgesic experiments using mice models including abdominal writhing induced by acetic acid, formalin-induced paw licking, and thermal pain test indicated that this two peptides exerted comparable analgesic activities with morphine. In addition, they had ability to inhibit inflammatory factor secretion induced by lipopolysaccharides (LPS). Considering their easy production, storage, transfer and potential analgesic activity, analgesin-HJs might be exciting leading compounds or templates for the development of novel analgesic agent. In addition, this study might facilitate to understand skin defensive mechanism of amphibians. PMID- 24211592 TI - Cholesterol biosynthesis and ER stress in peroxisome deficiency. AB - Cholesterol biosynthesis is a multi-step process involving more than 20 enzymes in several subcellular compartments. The pre-squalene segment of the cholesterol/isoprenoid biosynthetic pathway is localized in peroxisomes. This review intends to highlight recent findings illustrating the important role peroxisomes play in cholesterol biosynthesis and maintenance of cholesterol homeostasis. Disruption of the Pex2 gene leads to peroxisome deficiency and widespread metabolic dysfunction. The Pex2(-/-) mouse model for Zellweger syndrome enabled us to evaluate the role of peroxisomes in cholesterol biosynthesis. These studies have shown that Pex2(-/-) mice exhibit low levels of cholesterol in plasma and liver. Pex2(-/-) mice were unable to maintain normal cholesterol homeostasis despite activation of SREBP-2, the master transcriptional regulator of cholesterol biosynthesis, and increased protein levels and activities of cholesterol biosynthetic enzymes. The SREBP-2 pathway remained activated even after normalization of hepatic cholesterol levels in response to bile acid feeding as well as in extrahepatic tissues and the liver of neonatal and longer surviving Pex2 mutants, where cholesterol levels were normal. Several studies have shown that endoplasmic reticulum (ER) stress can dysregulate lipid metabolism via SREBP activation independently of intracellular cholesterol concentration. We demonstrated that peroxisome deficiency activates endoplasmic reticulum stress pathways in Pex2(-/-) mice, especially the integrated stress response mediated by PERK and ATF4 signaling, and thereby leads to dysregulation of the SREBP-2 pathway. Our findings suggest that functional peroxisomes are necessary to prevent chronic ER stress and dysregulation of the endogenous sterol response pathway. The constitutive activation of ER stress pathways might contribute to organ pathology and metabolic dysfunction in peroxisomal disorder patients. PMID- 24211593 TI - Dieckol, a phlorotannin isolated from a brown seaweed, Ecklonia cava, inhibits adipogenesis through AMP-activated protein kinase (AMPK) activation in 3T3-L1 preadipocytes. AB - In this study, we assessed the potential inhibitory effect of 5 species of brown seaweeds on adipogenesis the differentiation of 3T3-L1 preadipocytes into mature adipocytes by measuring Oil-Red O staining. The Ecklonia cava extract tested herein evidenced profound adipogenesis inhibitory effect, compared to that exhibited by the other four brown seaweed extracts. Thus, E. cava was selected for isolation of active compounds and finally the three polyphenol compounds of phlorotannins were obtained and their inhibitory effect on adipogenesis was observed. Among the phlorotannins, dieckol exhibited greatest potential adipogenesis inhibition and down-regulated the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer-binding proteins (C/EBPalpha), sterol regulatory element-binding protein 1 (SREBP1) and fatty acid binding protein 4 (FABP4) in a dose-dependent manner. The specific mechanism mediating the effects of dieckol was confirmed by AMP-activated protein kinase (AMPK) activation. These results demonstrate inhibitory effect of dieckol compound on adipogenesis through the activation of the AMPK signal pathway. PMID- 24211594 TI - The effects of cadmium chloride and sodium selenite on protein synthesis in mouse liver. AB - The study aimed at evaluating the effects of cadmium and selenite ions on protein synthesis and metallothioneins content in mice liver after 2 h, 8 h, 24 h and 14 days of exposure. Our studies revealed that cadmium suppressed protein synthesis after 2 h and 24 h, but activated after 8h and 14 days. Also, the endogenous mRNA translation were reduced under any exposure to cadmium, meanwhile, metallothioneins content was decreased after 2 h, but then was progressively increasing up to 492% after 14 days. Meantime, selenite did not influence metallothioneins content, caused mild activation of protein synthesis, and slightly suppressed the endogenous mRNA translation. The combined treatments with cadmium and selenite favored toward resisting of protein synthesis to cadmium after 2 h and 24 h of intoxication. Besides, selenite also protected translation against cadmium in cell-free systems, but did not attenuate effects of cadmium on metallothioneins content. PMID- 24211595 TI - A pilot study: the importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome. AB - Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism. Subjects were chronically exposed to low-to-moderate drinking water iAs. We analyzed well water, arsenic metabolites in urine, and toenail arsenic. Urine iAs and metabolites, toenail iAs, and secondary methylation efficiency increased as an effect of exposure (p<0.001). Urine iAs and metabolites showed a significant interaction effect between exposure and birth weight. Moderately exposed women with low compared to normal birth weight outcome had greater metabolite excretion (p<0.03); 67% with low compared to 10% with normal birth weight outcome presented urine iAs >9 MUg/L (p=0.019). Metabolic partitioning of iAs toward excretion may impair fetal growth. Prospective studies on iAs excretion before and during pregnancy may provide a biomarker for poor fetal growth risk. PMID- 24211596 TI - Neurotoxicity of neem commercial formulation (Azadirachta indica A. Juss) in adult zebrafish (Danio rerio). AB - The neurotoxic effects of a commercial formulation of Azadirachta indica A. Juss, also called neem or nim, in adult zebrafish were determined using behavioral models. General activity, anxiety-like effects, and learning and memory in a passive avoidance task were assessed after exposure to 20 or 40 MUl/L neem. The results showed that 20 MUl/L neem reduced the number of runs. Both neem concentrations increased the number of climbs to the water surface, and 40 MUl/L increased the number of tremors. In the anxiety test, the 20 MUl/L dose increased the number of entries in the light side compared with controls, but the latency to enter the dark side and the freezing behavior in this side did not changed. In relation to controls, the 40 MUl/L neem reduced the latency to enter in the light side, did not change the number of entries in this side and increased freezing behavior in the light side. In the passive avoidance test, pre-training and pre test neem exposure to 40 MUl/L decreased the response to the learning task. Thus, no impairment was observed in this behavioral test. We conclude that neem reduced general activity and increased anxiety-like behavior but did not affect learning and memory. PMID- 24211597 TI - Clinical evaluation of photodynamic therapy efficacy in the treatment of oral leukoplakia. AB - BACKGROUND: The aim of the study was clinical evaluation of photodynamic therapy efficacy in the treatment of oral leukoplakia lesions. METHODS: Twenty-three consecutive patients aged 21-79 were included to the study. In all patients 44 homogeneous, flat leukoplakia lesions were clinically diagnosed and confirmed histopathologically. Photodynamic therapy was performed with the use of Photolon((r)) photosensitizer, containing 20% Chlorine-e6 and 10% dimethyl sulfoxide and a semiconductor laser, with power up to 300mW and a wavelength of 660nm. Ten illumination sessions were conducted with the use of superficial light energy density of 90J/cm(2). RESULTS: At baseline the mean size of leukoplakia lesion was 6.5+/-5.10cm(2) while after photodynamic therapy 3+/-2.99cm(2). Significant reduction (on average by 53.8%) of leukoplakia lesions sizes was observed after therapy. Twelve (27.27%) lesions had been completely cured, 22 (50%) partially cured, although 10 (22.73%) lasted unchanged. The efficacy of PTD was comparable in women and men irrespective of age. There have been no adverse site effects during therapy noted. CONCLUSIONS: Within the limits of the study it can be concluded that photodynamic therapy with the use of Chlorine-e6 can lead to considerable reduction of oral leukoplakia lesions size thus may be useful in clinical practice. However there is a need of further studies on larger number of cases and longer follow-up time. PMID- 24211598 TI - Prostate cancer biomarker profiles in urinary sediments and exosomes. AB - PURPOSE: Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine collection was also studied and the prostate cancer specific biomarkers PCA3 and TMPRSS2-ERG were assayed. MATERIALS AND METHODS: Urine samples were prospectively obtained before and after digital rectal examination from 30 men scheduled for prostate biopsy. Cell pellet and exosomes were isolated and used for biomarker analysis. Analytical and diagnostic performance was tested using the Student t-test and ROC curves. RESULTS: Unlike the exosome fraction, urinary sediment gene expression analysis was compromised by amorphous precipitation in 10% of all specimens. Digital rectal examination resulted in increased mRNA levels in each fraction. This was particularly relevant for the exosomal fraction since after digital rectal examination the number of samples decreased in which cancer specific markers were below the analytical detection limit. Biomarker diagnostic performance was comparable to that in large clinical studies. In exosomes the biomarkers had to be normalized for prostate specific antigen mRNA while cell pellet absolute PCA3 levels had diagnostic value. CONCLUSIONS: Exosomes have characteristics that enable them to serve as a stable substrate for biomarker analysis. Thus, digital rectal examination enhances the analytical performance of biomarker analysis in exosomes and cell pellets. The diagnostic performance of biomarkers in exosomes differs from that of cell pellets. Clinical usefulness must be prospectively assessed in larger clinical cohorts. PMID- 24211599 TI - Outcome of metastasectomy for urothelial carcinoma: a multi-institutional retrospective study in Japan. AB - PURPOSE: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. MATERIALS AND METHODS: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. RESULTS: Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19-80) from the initiation of treatment for metastases and 26 months (IQR 11-90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). CONCLUSIONS: Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis. PMID- 24211600 TI - Population level assessment of hospital based outcomes following laparoscopic versus open partial nephrectomy during the adoption of minimally invasive surgery. AB - PURPOSE: The comparative outcomes of laparoscopic and open partial nephrectomy remain incompletely defined. Therefore, we used population based data to examine resource use and short-term outcomes among patients with kidney cancer treated with laparoscopic vs open partial nephrectomy. MATERIALS AND METHODS: Using linked SEER (Surveillance, Epidemiology, and End Results)-Medicare data we identified patients with kidney cancer treated with laparoscopic or open partial nephrectomy from 2000 through 2007. We then used Medicare claims to identify several postoperative outcomes including intensive care unit care, length of stay, rehospitalizations, operative mortality and postoperative complications. We fit multivariate logistic regression models to estimate the association between each outcome and surgical approach (ie laparoscopic partial nephrectomy vs open partial nephrectomy), adjusting for patient and tumor characteristics. RESULTS: We identified 651 (28%) and 1,670 (72%) patients treated with laparoscopic partial nephrectomy and open partial nephrectomy, respectively. Compared to those who underwent open partial nephrectomy, patients treated with laparoscopic partial nephrectomy had a 34% lower probability of requiring intensive care unit time (20.0% vs 30.2%, p <0.001) and shorter median length of stay (3 vs 5 days, p <0.001), with no differences observed in the likelihood of rehospitalization or operative mortality. While the frequency of postoperative complications was similar (35.5% vs 36.1%, p = 0.829), patients treated with laparoscopic partial nephrectomy had a nearly twofold greater probability of genitourinary complications and postoperative hemorrhage (p <0.001). CONCLUSIONS: At a population level the patients with kidney cancer treated with laparoscopic partial nephrectomy experienced a shorter and less intense hospitalization, supporting the benefits of laparoscopy. However, the greater likelihood of procedure related complications highlights the need for continued efforts aimed at ensuring the safe adoption and application of this advanced surgical technique. PMID- 24211601 TI - Surgeon assessment of renal preservation with partial nephrectomy provides information comparable to measurement of volume preservation with 3-dimensional image analysis. AB - PURPOSE: The strongest predictors of renal function after partial nephrectomy are the preoperative glomerular filtration rate and the amount of preserved parenchyma. Measuring volume preservation by 3-dimensional imaging is accurate but time-consuming. Percent functional volume preservation was designed to replace surgeon assessment of volume preservation with a less labor intensive, objective assessment. We compared volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation as predictors of renal function after partial nephrectomy. MATERIALS AND METHODS: We calculated volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation in 41 patients with preoperative and postoperative cross-sectional imaging available. Surgeon assessment was validated internally in another 75 patients. Short-term and long-term renal function was assessed with univariate and multivariate linear regression models. RESULTS: Median parenchymal preservation was 85% (range 37% to 105%) by 3-dimensional imaging, 91% (range 51% to 114%) by percent functional preservation and 88% (range 45% to 99%) by surgeon assessment. Each method strongly correlated with nadir glomerular filtration rate (r(2) = 0.75, 0.65 and 0.78) and latest glomerular filtration rate (r(2) = 0.65, 0.66 and 0.67, respectively, each p <0.0001). Univariate analysis revealed that age, preoperative glomerular filtration rate, renal nephrometry score and each assessment were significant predictors of renal function (p <0.05). On multivariate analysis parenchymal preservation was the strongest predictor (p <0.0001). Models using volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation were statistically similar in the ability to predict the nadir and latest glomerular filtration rates. In an additional validation cohort surgeon assessment remained strongly correlated with nadir glomerular filtration rate (r(2) = 0.74) and latest glomerular filtration rate (r(2) = 0.73, each p <0.0001). CONCLUSIONS: Surgeon assessment of volume preservation provides a reliable estimate of renal functional preservation with characteristics comparable to those of more time intensive alternatives. We propose that surgeon assessment of volume preservation should be routinely reported to facilitate analysis of partial nephrectomy outcomes. PMID- 24211602 TI - Screening carotid artery duplex in patients undergoing cardiac surgery. AB - BACKGROUND: We sought to determine the prevalence of carotid artery stenosis (CAS)>50% in a large, multi-institutional health maintenance organization found during duplex ultrasonography screening before cardiac surgery and to identify risk factors to increase the yield of a preoperative screening program. METHODS: This retrospective review study was conducted on 722 patients who had undergone duplex ultrasonography screening of the carotid artery before cardiac surgery between June 2008 and February 2011. The primary outcome was CAS>50% detected on duplex ultrasonography screening. RESULTS: Seven hundred twenty-two patients (66.2% men; median age: 71 years) underwent duplex ultrasonography screening of the carotid artery before cardiac surgery. The main indications for cardiac surgery were valvular disease (39.5%) and coronary artery disease (36.3%). One hundred eighteen patients (16.3%) had CAS>=50%. Among the patients found to have carotid stenosis, 38 patients (32.2%) had bilateral stenosis>50% and 37 patients (31.4%) had at least 70% unilateral stenosis. The presence of peripheral vascular disease (odds ratio [OR]: 2.93 [95% confidence interval {CI}: 1.87-4.60]; P<0.001), and history of cerebrovascular disease within 12 months (OR: 4.57 [95% CI: 1.18-17.77]; P=0.028) were risk factors associated with CAS. Patients who have coronary artery disease with cardiac catheterization showing left main disease (OR: 6.80 [95% CI: 3.02-15.29]; P<0.001), 3-vessel disease or more (OR: 2.78 [95% CI: 1.43-5.43]; P=0.003), or both (OR: 4.13 [95% CI: 1.89-9.06]; P<0.001) were found to be significantly more likely to have CAS>50%. CONCLUSIONS: Independent risk factors that are predictive of the presence of CAS are peripheral vascular disease, having had a previous cerebrovascular accident, and coronary artery disease with left main or 3-vessel disease. Routine carotid duplex ultrasonography scanning may not be necessary for all patients undergoing cardiac surgery, and selective carotid screening programs may be considered in patients with symptomatic atherosclerosis disease or advanced coronary artery disease. PMID- 24211603 TI - Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network. AB - Endocrine disrupting chemicals have been shown to alter the pubertal process. The controlling levels of the Gonadotropin releasing hormone (GnRH) network involve GnRH itself, KiSS1, and the transcriptional regulators enhanced at puberty 1 (EAP1), Thyroid Transcription Factor 1 (TTF1), and Yin Yang 1 (YY1). While Genistein and Bisphenol A (BPA) have been shown to advance the advent of puberty, exposure to Dioxin delayed pubertal onset. Utilizing in vitro approaches, we observed that Genistein and BPA suppress inhibitory and activate stimulatory components of the GnRH network, while Dioxin exhibit an inhibitory effect at all regulatory hierarchical levels of the GnRH network. It repressed KiSS1, Gnrh, Ttf1 and Yy1 transcription via the xenobiotic response element (XRE), while EAP1 was not affected. Therefore, EDCs alter the neuroendocrine GnRH regulatory network at all hierarchical levels. PMID- 24211604 TI - Stabilization of G-quadruplex DNA and inhibition of telomerase activity studies of ruthenium(II) complexes. AB - Two ruthenium(II) complexes [Ru(IP)2(PIP)](ClO4)2.2H2O (1) and [Ru(PIP)2(IP)](ClO4)2.2H2O (2) (IP=imidazole [4, 5-f] [1,10] phenanthroline, PIP=2-phenylimidazo-[4, 5-f][1,10] phenanthroline) have been synthesized and characterized. The quadruplex binding of the compounds was evaluated by emission spectrum, CD spectroscopy, Visual detection assay and FRET (fluorescence resonance energy transfer)-melting assay. The results show that both complexes can induce the stabilization of quadruplex DNA, while complex 1 is a better G quadruplex binder than complex 2. Furthermore, polymerase chain reaction-stop assay, electrophoretic mobility shift assay, telomerase repeat amplification protocol and MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay demonstrate that complex 1 not only can stabilize dimer forms of the G quadruplex at low concentrations but also exhibit better inhibitory activity for telomerase and cancer cells. PMID- 24211605 TI - Lipid modulation of ion channels through specific binding sites. AB - Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids. The fact that this protein is able to assemble into clusters through the same non-annular sites, resulting in large changes in channel activity, makes these sites even more interesting as a potential target to develop lead compounds able to disrupt such interactions and hopefully, to modulate ion channel function. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. PMID- 24211606 TI - Evaluation of eight agar media for the isolation of shiga toxin-Producing Escherichia coli. AB - The growth characteristics of 96 shiga toxin-producing Escherichia coli (STEC) strains representing 36 different O-types (including priority O types O26, O45, O103, O111, O121, O145 and O157) on commercial and in-house agar media were studied. The ability of the strains to grow on agar media with varying selective supplement formulations was evaluated using MacConkey Agar (MAC); Rainbow(r) Agar O157 (RBA); Rainbow(r) Agar O157 with manufacturer-recommended selective supplements (RBA-NT); Rainbow(r) Agar O157 with USDA-recommended selective supplements (RBA-USDA); CHROMagar STECTM (CH STEC); Tryptone Bile agar containing cefixime and tellurite (TBA-CT); Tryptone Bile agar containing cefixime, tellurite, eosin and methylene blue (TBA-EM); and VTEC agar. All of the strains were able to grow on MAC, RBA and VTEC agar, whereas a number of strains (including some non-O157 priority O types) were unable to grow on the highly selective media CH STEC, RBA-NT, RBA-USDA, TBA-EM and TBA-CT. Only RBA-NT and CH STEC exhibited significant inhibition of background flora from ground beef enrichment. Significant inhibition of background flora from beef trim enrichment was observed with RBA-NT, RBA-USDA, CH STEC, TBA-EM and VTEC agar. With exception of E. coli O157, several different colony morphologies were observed on the differential plating media among strains of the same O type, indicating that this colony morphology is not a reliable means of identifying target STEC. These results suggest that an approach to maximize the recovery of target STEC from beef enrichment cultures is dual plating on lesser (RBA, MAC, VTEC agar) and more highly (RBA-NT, CH STEC) selective agars. PMID- 24211607 TI - Phenotypic and genomic characterization of human coxsackievirus A16 strains with distinct virulence in mice. AB - Human coxsackievirus A16 (CA16) infection results in hand, foot, and mouth disease (HFMD) along with other severe neurological diseases in children and poses an important public health threat in Asian countries. During an HFMD epidemic in 2009 in Guangdong, China, two CA16 strains (GD09/119 and GD09/24) were isolated and characterized. Although both strains were similar in plaque morphology and growth properties in vitro, the two isolates exhibited distinct pathogenicity in neonatal mice upon intraperitoneal or intracranial injection. Complete genome sequences of both CA16 strains were determined, and the possible virulence determinants were analyzed and predicted. Phylogenetic analysis revealed that these CA16 isolates from Guangdong belonged to the B1b genotype and were closely related to other recent CA16 strains isolated in mainland China. Similarity and bootscanning analyses of these CA16 strains detected homologous recombination with the EV71 prototype strain BrCr in the non-structural gene regions and the 3'-untranslated regions. Together, the phenotypic and genomic characterizations of the two clinical CA16 isolates circulating in China were compared in detail, and the potential amino acid residues responsible for CA16 virulence in mice were predicted. These findings will help explain the evolutionary relationship of the CA16 strains circulating in China, warranting future studies investigating enterovirus virulence. PMID- 24211608 TI - Induction and control of the type I interferon pathway by Bluetongue virus. AB - The innate immune response is the first line of defence against viruses, involving the production of type I IFN (IFN-alpha/beta) and other pro inflammatory cytokines that control the infection. It also shapes the adaptive immune response generated by both T and B cells. Production of type I IFN occurs both in vivo and in vitro in response to Bluetongue virus (BTV), an arthropod borne virus. However, the mechanisms responsible for the production of IFN-beta in response to BTV remained unknown until recently and are still not completely understood. In this review, we describe the recent advances in the identification of cellular sensors and signalling pathways involved in this process. The RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) were shown to be involved in the expression of IFN-beta as well as in the control of BTV infection in non-haematopoietic cells. In contrast, induction of IFN-alpha/beta synthesis in sheep primary plasmacytoid dendritic cells (pDCs) required the MyD88 adaptor independently of the Toll-like receptor 7 (TLR7), as well as the kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK). As type I IFN is essential for the establishment of an antiviral cellular response, most of viruses have elaborated counteracting mechanisms to hinder its action. This review also addresses the ability of BTV to interfere with IFN-beta synthesis and the recent findings describing the non-structural viral protein NS3 as a powerful antagonist of the host cellular response. PMID- 24211609 TI - Evolutionary repurposing of endosomal systems for apical organelle biogenesis in Toxoplasma gondii. AB - It is very difficult to define an endocytic system in Toxoplasma gondii. The parasite does not appear to take up exogenous materials via classical endocytosis. The presence of Rab5 and Rab7, classical markers of endocytic compartments, and their decoration of endomembranous structures suggest, however, that an endosomal-like system may operate. Additionally, new findings reveal that dynamin and the transmembrane type-I receptor sortilin are involved in the biogenesis of T. gondii micronemes and rhoptries, unique apical secretory organelles required for parasite migration and host-cell invasion, manipulation and egress. Evidence suggests that the parasite uses an endosomal-like system to traffic and sort proteins to rhoptries and micronemes via the endoplasmic reticulum and Golgi. In this review, I discuss recent findings suggesting that T. gondii and other apicomplexans have reduced their endosomal system and repurposed the evolutionarily conserved regulators of the system to build the apical secretory organelles. This review is also intended to serve as a resource for future investigations of apicomplexan biology and evolution. PMID- 24211610 TI - Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients. AB - BACKGROUND: Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. PATIENTS AND METHODS: In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days after intravenous anti rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4+ T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4+ T cells and the trough levels of tacrolimus and cyclosporine were also measured. RESULTS: The ATP level detected on the day AR occurred (627.07+/-149.85ng/ml) was obviously higher than that of the stable group (320.48+/-149.11ng/ml, P<0.05). ATP value decreased to 265.35+/-84.33ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87+/-162.85ng/ml, P<0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55ng/ml. A positive correlation between the intracellular ATP level and absolute CD4+ T cell number (r=0.656, P<0.001) was found in the patients with CD4+ T cell counts <200/MUl. PMID- 24211611 TI - A novel carboxymethyl chitosan-quantum dot-based intracellular probe for Zn2+ ion sensing in prostate cancer cells. AB - In this paper, we fabricated novel carboxymethyl chitosan-coated CdTe quantum dots (CMC-CdTe QDs) via the electrostatic interaction between amino groups in the carboxymethyl chitosan polymeric chains and carboxyl groups of the CdTe QDs. Carboxymethyl chitosan on the surface of CdTe QDs had strong binding ability with Zn(2+), resulting in the obvious enhancement of the photoluminescence of CdTe QDs. The photoluminescence intensity of CMC-CdTe QDs probe was proportional to the concentration of Zn(2+) in the range of 5.0 * 10(-6) to 5.0 * 10(-3) mol l( 1). The detection limit for Zn(2+) was 4.5 * 10(-6) mol l(-1). The experimental results indicate that the CMC-CdTe QDs possess favorable cell compatibility, good sensitivity and selectivity for intracellular Zn(2+) sensing, and are promising candidates for cellular imaging and sensing in prostate cancer cells. The present study also provides an approach for the further development of nanoprobes dedicated to intracellular sensing. PMID- 24211613 TI - Structural network analysis of biological networks for assessment of potential disease model organisms. AB - Model organisms provide opportunities to design research experiments focused on disease-related processes (e.g., using genetically engineered populations that produce phenotypes of interest). For some diseases, there may be non-obvious model organisms that can help in the study of underlying disease factors. In this study, an approach is presented that leverages knowledge about human diseases and associated biological interactions networks to identify potential model organisms for a given disease category. The approach starts with the identification of functional and interaction patterns of diseases within genetic pathways. Next, these characteristic patterns are matched to interaction networks of candidate model organisms to identify similar subsystems that have characteristic patterns for diseases of interest. The quality of a candidate model organism is then determined by the degree to which the identified subsystems match genetic pathways from validated knowledge. The results of this study suggest that non obvious model organisms may be identified through the proposed approach. PMID- 24211612 TI - Nonlinear viscoelastic characterization of the porcine spinal cord. AB - Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted root mean squared error for a Heaviside ramp fit was 2.8 kPa, which was significantly greater (p<0.001) than that of the nonlinear (comprehensive viscoelastic characterization method) fit (0.365 kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high-resolution finite elements models of the spine. PMID- 24211615 TI - Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy. AB - AIMS: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. MAIN METHODS: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR). KEY FINDINGS: The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats. SIGNIFICANCE: Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR. PMID- 24211614 TI - Endothelin-1 stimulates catalase activity through the PKCdelta-mediated phosphorylation of serine 167. AB - Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and in lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine-phosphorylated catalase. Using the inhibitory peptide deltaV1.1, this phosphorylation was shown to be protein kinase Cdelta (PKCdelta) dependent. Mass spectrometry identified serine 167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from Escherichia coli or transiently transfected COS-7 cells demonstrated that S167D catalase had an increased ability to degrade H2O2 compared to the wild-type enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist tezosentan. S167 is located on the dimeric interface, suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel filtration to examine the multimeric structure of recombinant wild-type and S167D catalase. We found that recombinant wild-type catalase was present as a mixture of monomers and dimers, whereas S167D catalase was primarily tetrameric. Further, the incubation of wild-type catalase with PKCdelta was sufficient to convert wild type catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity. PMID- 24211617 TI - A bufadienolide derived androgen receptor antagonist with inhibitory activities against prostate cancer cells. AB - Molecular docking studies have shown that Delta(8,14)-anhydrobufalin (1) exhibited more potent binding affinity on androgen receptor (AR) than Delta(14,15)-anhydrobufalin (2) and bufalin (3). To validate the docking results, compounds 1 and 2 were synthesized. The AR competitive binding assay indicated that the IC50 values of 1-3 were 1.9, >50 and >50MUM (relative binding affinity), respectively, which confirmed that our theoretical binding mode was reliable and predictable. Furthermore, compound 1 was found to show more potent inhibitory activity against the androgen dependent LNCaP cancer cells than the androgen independent PC3 cancer cells, but exhibited less inhibition on the Na(+)/K(+) ATPase as compared with the parent compound 3. To the best of our knowledge, compound 1 represented the first AR antagonist derived from bufadienolide discovered through a series of combined approaches of molecular docking and actual experimental validation. PMID- 24211616 TI - Disruption of oxidative phosphorylation and synaptic Na(+), K(+)-ATPase activity by pristanic acid in cerebellum of young rats. AB - AIMS: Peroxisomal biogenesis disorders (PBD) are inherited disorders clinically manifested by neurological symptoms and brain abnormalities, in which the cerebellum is usually involved. Biochemically, patients affected by these neurodegenerative diseases accumulate branched-chain fatty acids, including pristanic acid (Prist) in the brain and other tissues. MAIN METHODS: In the present investigation we studied the in vitro influence of Prist, at doses found in PBD, on oxidative phosphorylation, by measuring the activities of the respiratory chain complexes I-IV and ATP production, as well as on creatine kinase and synaptic Na(+), K(+)-ATPase activities in rat cerebellum. KEY FINDINGS: Prist significantly decreased complexes I-III (65%), II (40%) and especially II-III (90%) activities, without altering the activities of complex IV of the respiratory chain and creatine kinase. Furthermore, ATP formation and synaptic Na(+), K(+)-ATPase activity were markedly inhibited (80-90%) by Prist. We also observed that this fatty acid altered mitochondrial and synaptic membrane fluidity that may have contributed to its inhibitory effects on the activities of the respiratory chain complexes and Na(+), K(+)-ATPase. SIGNIFICANCE: Considering the importance of oxidative phosphorylation for mitochondrial homeostasis and of Na(+), K(+)-ATPase for the maintenance of cell membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission in cerebellum. We postulate that these pathomechanisms may contribute to the cerebellar alterations observed in patients affected by PBD in which Prist is accumulated. PMID- 24211618 TI - Enhanced antioxidant effect of caffeic acid phenethyl ester and Trolox in combination against radiation induced-oxidative stress. AB - Combinations of antioxidants are believed to be more effective than single antioxidant because when antioxidants are combined they support each other synergistically to create a magnified effect. Discovering the enhancer effects or synergies between bioactive components is valuable for resisting oxidative stress and improving health benefits. The aim of this study was to investigate a possible cooperation of natural antioxidant caffeic acid phenethyl ester (CAPE) with synthetic antioxidant Trolox in the model systems of chemical generation of free radicals, lipid peroxidation of microsomes and radiation-induced oxidative injury in L929 cells. Based on the intermolecular interaction between CAPE and Trolox, the present study shows a synergistic effect of CAPE and Trolox in combination on elimination of three different free radicals and inhibition of lipid peroxidation initiated by three different systems. CAPE and Trolox added simultaneously to the L929 cells exerted an enhanced preventive effect on the oxidative injury induced by radiation through decreasing ROS generation, protecting plasma membrane and increasing the ratios of reduced glutathione/oxidized glutathione and the expression of key antioxidant enzymes mediated by nuclear factor erythroid 2 p45-related factor 2 (Nrf2). Our results showed for the first time that administration of CAPE and Trolox in combination may exert synergistic antioxidant effects, and further indicate that CAPE and Trolox combination functions mainly through scavenging ROS directly, inhibiting lipid peroxidation and promoting redox cycle of GSH mediated by Nrf2-regulated glutathione peroxidase and glutathione reductase expression. PMID- 24211619 TI - Two new metastable forms of 6-chloroquinolin-2(1H)-one: crystal structure, Hirshfeld surfaces and spectroscopic studies. AB - Two new metastable crystalline forms of 6-chloroquinolin-2(1H)-one (forms II and III), which were induced by two kinds of 3D inorganic anions (ClO4- and BF4-), have been prepared and characterized in this work. We performed single-crystal diffraction, X-ray powder diffraction (XRPD), Hirshfeld surfaces, solid-state vibrational spectroscopy (IR) and thermal analysis (DSC, TGA) to these two new forms as well as the original one (form I). Form I featured with 1D chain, while form II and III featured with dimeric unit with stronger pi?pi and hydrogen bonds interactions. The 3D inorganic anions force the self-assemble behavior of 6 chloroquinolin-2(1H)-one molecules from 1D chain structure (form I) to dimeric unit (forms II and III) due to their large steric hindrance, and different anions induced different orientations for dimeric unit. These transformations lead to the increase of N-H?O, pi?pi, and Cl-Cl intermolecular interactions, which lead to blue shift of IR spectra in 1700-1500 cm(-1) region as well as luminescence peaks, while red shift of IR spectra in 650-550 cm(-1) region. PMID- 24211620 TI - Optical properties of 1-(4,5-diphenyl-1-p-tolyl-1H-imidazol-2-yl)naphthalen-2-ol- ESIPT process. AB - This article presents optical, electrochemical, and thermal properties of novel class of green fluorescent 1-(4,5-diphenyl-1-p-tolyl-1H-imidazol-2-yl)naphthalen 2-ol. Detailed photo physical and quantum chemical studies have been performed to elucidate the excited state intramolecular proton transfer (ESIPT) reaction leading a large stokes shifted fluorescence emission from the phototautomer. The results of quantum chemical investigations confirmed the intramolecular charge transfer characteristics of the ESIPT tautomers. The high photoluminescence quantum yield is ascribed to twisted chromophores due to phenyl substituents at 1,2-position of the imidazole ring which restricted intramolecular motion, leading to an optically allowed lowest optical transition without self quenching. PMID- 24211621 TI - CaTiO3:Eu3+ red nanophosphor: low temperature synthesis and photoluminescence properties. AB - Nanoparticles of Eu3+ doped (1-9 mol%) CaTiO3 were prepared using low temperature (500 degrees C) solution combustion technique using metal nitrates as precursors and urea as fuel. The powder X-ray diffraction patterns of the as-formed products show single orthorhombic phase. The crystallite size was estimated using Scherrer's method and found to be in the range 40-45 nm. The effect of Eu3+ ions on luminescence characteristics of CaTiO3 was studied and the results were discussed in detail. The phosphors exhibit bright red emission upon 398 nm excitation. The characteristic emission peaks recorded at ~540, 593, 615, 653, 696 and 706 nm (5D0->7Fj=0,1,2,3,4,5) were attributed to Eu3+ ions. The electronic transition corresponding to 5D0->7F2 (615 nm) was stronger than the magnetic dipole transition 5D0->7F1 of Eu3+ ions (596 nm). The CIE chromaticity co-ordinates were calculated from emission spectra, the values (x,y) very close to NTSC standard value of red emission. Therefore, the present phosphors were highly useful for display applications. PMID- 24211622 TI - A novel cobalt (I) coordination polymer with mixed thiocyanate and quinoline ligands: crystal structure, magnetism and luminescent properties. AB - A new Co(I) one-dimensional coordination polymer [Co(SCN)(ql)]n (ql=quinoline) (1) has been synthesized and characterized by IR, elemental analysis, TG technique and X-ray crystallography. Co(I) atom has a distorted trigonal pyramidal N2S2 (1) environment with two S atoms and one N atom from three MU 1,1,3-thiocyanate bridge ligands and one N atom from ql ligand. Two S atoms from two MU-1,1,3-SCN- bridging ligands bridge two centers to obtain bimetallic 4 membered ring. Adjacent 4-membered rings are linked by a pair of MU-1,1,3-SCN- bridging ligands to form a 1D stair-case like chain. The luminescent properties and magnetic properties of the polymer 1 were investigated in the solid state. PMID- 24211623 TI - Conformational analysis and vibrational study of daidzein by using FT-IR and FT Raman spectroscopies and DFT calculations. AB - Daidzein (C15H10O4) is a type of isoflavone. It was isolated from Butea monosperma that belongs to the Fabaceae family. Soybeans and soy products are the abundant source of daidzein. It is the subject of investigation for many reasons, as it has got wide applications, such as anti-tumor, anti-estrogen, weak pro estrogen and anti-cancer activities. In the present study, a complete vibrational assignment is provided for the observed IR and Raman spectra of daidzein. Electronic properties have been analyzed using TD-DFT method for both gaseous and solvent phase. The optimized geometry, total energy, potential energy surface and vibrational wavenumbers of daidzein have been determined using density functional theory (DFT/B3LYP) method with 6-311++G(d,p) basis set and a good correlation was found between observed and calculated values. The double well potential energy curve of the molecule about three bonds, has been plotted, as obtained from DFT/6 31G basis. The HOMO-LUMO energy gap of possible conformers has been calculated for comparing their chemical activity. Global reactivity descriptors have been calculated for predicting the chemical reactivity and the stability of chemical systems. Electrostatic potential surface has been plotted for predicting the structure activity relationship. NBO analysis has also been performed to study the stability of the molecule. NLO study reveals the nonlinear properties of the molecule. 1H and 13C NMR spectra have also been studied. Finally, the calculated results were used to simulate infrared and Raman spectra of the title compound which showed a good agreement with the observed spectra. PMID- 24211624 TI - Facile synthesis of silver chloride nanoparticles using marine alga and its antibacterial efficacy. AB - Exploitation of advancements in antimicrobial agent synthesis assisted by nanomaterials has received considerable attention in the recent years. Based on this, an eco-friendly approach for the synthesis of silver chloride nanoparticles (AgClNPs) using aqueous extract of Sargassum plagiophyllum is emphasized. UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), high resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FESEM) were used to characterize the formation of AgClNPs. X-ray diffraction (XRD) patterns clearly illustrate the presence of AgClNPs. The synthesized AgClNPs were tested for its antibacterial activity and it was found to cause considerable amount of deterioration to bacterial cells, when examined using electron microscope and cell viability analysis. PMID- 24211625 TI - Better than sleep: theta neurofeedback training accelerates memory consolidation. AB - Consistent empirical results showed that both night and day sleep enhanced memory consolidation. In this study we explore processes of consolidation of memory during awake hours. Since theta oscillations have been shown to play a central role in exchange of information, we hypothesized that elevated theta during awake hours will enhance memory consolidation. We used a neurofeedback protocol, to enhance the relative power of theta or beta oscillations. Participants trained on a tapping task, were divided into three groups: neurofeedback theta; neurofeedback beta; control. We found a significant improvement in performance in the theta group, relative to the beta and control groups, immediately after neurofeedback. Performance was further improved after night sleep in all groups, with a significant advantage favoring the theta group. Theta power during training was correlated with the level of improvement, indicating a clear relationship between memory consolidation, and theta neurofeedback. PMID- 24211626 TI - Tissue kallikrein mediates neurite outgrowth through epidermal growth factor receptor and flotillin-2 pathway in vitro. AB - Tissue kallikrein (TK) was previously shown to take most of its biological effects through bradykinin receptors. In this study, we assumed that TK mediated neurite outgrowth was independent of bradykinin receptors. To test the hypothesis, we investigated TK-induced neurite outgrowth and its signaling mechanisms in cultured primary neurons and human SH-SY5Y cells. We found that TK stimulation could increase the number of processes and mean process length of primary neurons, which were blocked by epidermal growth factor receptor (EGFR) inhibitor or down-regulation, small interfering RNA for flotillin-2 and extracellular signal-regulated kinase (ERK) 1/2 inhibitor. Moreover, TK-induced neurite outgrowth was associated with EGFR and ERK1/2 activation, which were inhibited by EGFR antagonist or RNA interference and flotillin-2 knockdown. Interestingly, inhibition of bradykinin receptors had no significant effects on EGFR and ERK1/2 phosphorylation. In the present research, our data also suggested that EGFR and flotillin-2 formed constitutive complex that translocated to around the nuclei in the TK stimulation. In sum, our findings provided evidence that TK could promote neurite outgrowth via EGFR, flotillin-2 and ERK1/2 signaling pathway in vitro. PMID- 24211627 TI - ENSA expression correlates with attenuated tumor propagation in liver cancer. AB - Endosulfine alpha (ENSA) is an endogenous ligand of sulfonylurea receptor that was reported to be associated with an ATP-dependent potassium channel that controls insulin release and the onset of type 2 diabetes. ENSA also interacts with microtubule-associated serine/threonine-protein kinase-like (MASTL) to regulate the cell cycle. Previously, we identified ENSA as a possible bivalent gene in mesenchymal stem cells (MSCs) and hypothesized its methylation might determine cellular differentiation and transformation. Because there was no link between aberrant ENSA expression and tumorigenesis, we aimed to determine if ENSA is abnormally regulated in liver cancer and plays a role in liver cancer propagation. The epigenetic states of the ENSA promoter were evaluated in different cancer cell lines and patient samples. ENSA was overexpressed in a liver cancer cell line, and its interaction with MASTL and possible tumor suppression capabilities were also determined in cultured cells and mice. Distinct ENSA promoter methylation was observed in liver cancer (n=100 pairs) and breast cancer (n=100 pairs). ENSA was predominantly hypomethylated in liver cancer but was hypermethylated in breast cancer. Overexpressed ENSA interacts with MASTL and suppresses hepatic tumor growth. We also found that ENSA is hypermethylated in CD90-expressing (CD90(+)) cells compared to CD90 non expressing (CD90(-)) liver cancer cells. These data reveal ENSA methylation changes during hepatic tumor evolution. Overexpressed ENSA suppresses tumor growth in an established hepatic cell line whereas hypermethylated ENSA might help maintain liver cancer initiating cells. PMID- 24211628 TI - Survival analysis of acquired immune deficiency syndrome patients with and without hepatitis C virus infection at a reference center for sexually transmitted diseases/acquired immune deficiency syndrome in Sao Paulo, Brazil. AB - INTRODUCTION: Survival of patients with acquired immune deficiency syndrome has improved with combination antiretroviral therapy; mortality due to liver diseases, however, has also increased in these patients. OBJECTIVES: To estimate the accumulated probability of survival in human immunodeficiency virus-hepatitis C virus coinfected and non-coinfected patients and to investigate factors related to acquired immune deficiency syndrome patients' survival. METHODS: Non concurrent cohort study using data from surveillance information systems of acquired immune deficiency syndrome patients over 13 years of age. Hepatitis C and B, human immunodeficiency virus exposure category, CD4+ T cell count, age group, schooling, race, sex, and four acquired immune deficiency syndrome diagnosis periods were studied. Kaplan-Meier survival analysis and Cox model with estimates of the hazard ratio and 95% confidence interval were used. RESULTS: Of the total 2864 individuals included, with median age was 35 years, 219 died (7.5%), and 358 (12.5%) were human immunodeficiency virus-hepatitis C virus coinfected. The accumulated probability of survival in human immunodeficiency virus-hepatitis C virus coinfected patients, after acquired immune deficiency syndrome diagnosis, at 120 months, was 0%, 38.9%, 83.8% in 1986-1993, 1994-1996, 1997-2002, respectively, and 92.8% at 96 months in 2003-2010; survival in non coinfected patients at 120 months was 80%, 90.2%, 94% in 1986-1993, 1994-1996, 1997-2002, respectively, and 94.1% at 96 months in 2003-2010. In the multivariate model the following variables were predictive of death: hepatitis C virus coinfection (hazard ratio=2.7; confidence interval 2.0-3.6); Hepatitis B virus coinfection (hazard ratio=2.4; confidence interval 1.7-3.6); being >= 50 years old (hazard ratio=2.3; confidence interval 1.3-3.8); having 8-11 years of schooling (hazard ratio=1.6; confidence interval 1.1-2.3), having 4-7 years of schooling (hazard ratio=1.9; confidence interval 1.3-2.8) and having up to 3 years of schooling (hazard ratio=3.3; confidence interval 2.0-5.5). CONCLUSIONS: Among patients diagnosed after 1996, there was a significant increase in the cumulative probability of survival in human immunodeficiency virus-hepatitis C virus coinfected individuals; among those diagnosed with acquired immune deficiency syndrome from 2003 to 2010, this probability was similar between coinfected and non-coinfected patients. PMID- 24211629 TI - Cervical spondylitis and spinal abscess due to Actinomyces meyeri. AB - Human actinomycosis with involvement of the spine is a rare condition although it has been first described a long time ago. It is probably underrecognized since its clinical presentation is often misleading and accurate bacteriological diagnosis is challenging. We herein report a rare case of cervical actinomycosis with paravertebral abscess and spondylitis imputed to an infection by Actinomyces meyeri in a 52-year-old immunocompetent Caucasian man. A. meyeri should be considered as a potential cause for subacute or chronic spondylitis, even in immunocompetent subjects. Modern diagnostic tools such as Matrix-Assisted Laser Desorption-Ionization Time of Flight mass spectrometry and 16S rRNA sequencing are efficient for accurate microbiological identification. PMID- 24211630 TI - Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents. AB - This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl 2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2 hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed. PMID- 24211631 TI - Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4alpha- and 4beta-hydroxycholesterol) and C7 (7-ketocholesterol, 7alpha- and 7beta-hydroxycholesterol) on cells of the central nervous system. AB - Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7beta-hydroxycholesterol (7beta-OHC), 7alpha-hydroxycholesterol (7alpha OHC)) are well documented, those of oxysterols oxidized at C4 (4beta hydroxycholesterol (4beta-OHC), 4alpha-hydroxycholesterol (4alpha-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4beta-OHC and 4alpha-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7KC, 7beta-OHC, and 7alpha-OHC is associated with a decrease of cell viability (cytotoxic activities), our data establish that 4beta-OHC and 4alpha-OHC have no effect on cell viability, and no or minor effect on cell growth evocating cytostatic properties. Thus, comparatively to oxysterols oxidized at C7, the toxicity of oxysterols oxidized at C4 is in the following range of order: 7KC >= 7beta-OHC > 7alpha-OHC > (4beta-OHC >= 4alpha-OHC). Interestingly, to date, 4beta-OHC and 4alpha-OHC are the only oxysterols identified with cytostatic properties suggesting that these molecules, whereas not cytotoxic, may have some interests to counteract cell proliferation. PMID- 24211632 TI - Synthesis and antiproliferative activity of alpha-branched alpha,beta-unsaturated ketones. AB - A series of alpha-branched alpha,beta-unsaturated ketones were prepared in a straightforward manner by the acid catalyzed coupling between arylalkynes and carbaldehydes. The method also allows producing as side product chalcone analogs bearing an additional alpha,beta-unsaturated arylketone in the molecular scaffold. The evaluation of the antiproliferative activity in the human solid tumor cell lines HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T 47D (breast) and WiDr (colon) provided a structure-activity relationship. Overall, the compounds presented active against the resistant cancer cells T-47D. The resulting lead, displaying an unprecedented chalcone scaffold, showed GI50 values in the range 0.32-0.53 MUM against all cell lines tested. The methoxy group present in the lead might play an important role in the activity. PMID- 24211633 TI - Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-alpha based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation. AB - A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3 triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-alpha inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra pi-pi bond. The histopathology report showed that none of the compounds caused gastric ulceration. PMID- 24211634 TI - Co(II) and Cu(II) pyrophosphate complexes have selectivity and potency against Mycobacteria including Mycobacterium tuberculosis. AB - Tuberculosis (TB) causes up to 10 million incident cases worldwide per annum. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are leading factors in the resurgence of TB cases and the need to produce new agents to combat such infection. Herein, we describe Co(II) and Cu(II) metal based complexes that feature the pyrophosphate ligand with notable selectivity and marked potency against Mycobacterium tuberculosis, including MDR strains. Such complexes are confirmed to be bacteriocidal and not affected by efflux inhibitors. Finally, while susceptibility to copper has recently been established for M. tuberculosis, the greater efficacy of cobalt observed herein is of considerable note and in line with the discovery of a copper metallothionein in M. tuberculosis. PMID- 24211635 TI - Indole diterpene alkaloids as novel inhibitors of the Wnt/beta-catenin pathway in breast cancer cells. AB - Penitrems are indole diterpene alkaloids best known for their BK channel inhibition and tremorgenic effects in mammals. In a previous study, penitrems A-F (1-5), their biosynthetic precursors, paspaline (6) and emindole SB (7), and two brominated penitrem analogs 8 and 9 demonstrated promising in vitro antiproliferative, antimigratory, and anti-invasive effects in the MTT (MCF-7 and MDA-MB-231), wound-healing, and Cultrex BME cell invasion (MDA-MB-231) assays, respectively. The study herein reports the novel ability of penitrem A to suppress total beta-catenin levels in MDA-MB-231 mammary cancer cells. Nine new penitrem analogs (10-18) were semisynthetically prepared, in an attempt to identify pharmacophores correlated with BK channel inhibition and tremorgenicity of penitrems and decrease their toxicity. The degree of BK channel inhibition was assessed using the nematode Caenorhabditis elegans, and in vivo tremorgenic EC50 was calculated using CD-1 male mice following an Up-and-Down Procedure (UDP). Although new analogs were generally less active than parent compound 1, some showed no BK channel inhibition or tremorgenicity and retained the ability of penitrem A (1) to suppress total beta-catenin levels in MDA-MB-231 cells. Paspaline (6) and emindole SB (7), both lacking BK channel inhibition and tremorgenicity, represent the simplest indole diterpene skeleton that retains the antiproliferative, antimigratory and total beta-catenin suppressing effects shown by the more complex penitrem A (1). PMID- 24211636 TI - Skeletal hybridization and PfRIO-2 kinase modeling for synthesis of alpha-pyrone analogs as anti-malarial agent. AB - The pharmacophoric hybridization and computational design approach were applied to generate a novel series of alpha-pyrone analogs as plausible anti-malarial lead candidate. A putative active site in flexible loop close to wing-helix domain of PfRIO2 kinase was explored computationally to understand the molecular basis of ligand binding. All the synthesized molecules (3a-g) exhibited in vitro antimalarial activity. Oxidative stress induced by 3a-d were calculated and found to be significantly higher in case of 3b. Therefore, 3b, which shown most significant result was identified as promising lead for further SAR study to develop potent anti-malarials. PMID- 24211637 TI - Advances in the studies of roles of Rho/Rho-kinase in diseases and the development of its inhibitors. AB - RhoA/Rho-kinase pathway plays a pivotal role in numerous fundamental cellular functions including contraction, motility, proliferation, differentiation and apoptosis. The pathway is also involved in the development of many diseases such as vasospasm, pulmonary hypertension, cancer and central nervous systems (CNS) disorders. The inhibitors of Rho kinase have been extensively studied since the Rho/Rho-kinase pathway was verified as a target for a number of diseases. Herein, we reviewed the advances in the studies of the roles of Rho/Rho-kinase in diseases and the development of Rho-kinase inhibitors in recent five years. PMID- 24211638 TI - Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. AB - Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC50 = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study. PMID- 24211639 TI - Design, synthesis and evaluation of a cellular stable and detectable biotinylated fumagillin probe and investigation of cell permeability of fumagillin and its analogs to endothelial and cancer cells. AB - Fumagillin (1), a natural product of fungal origin, and its analogs were discovered to be extremely potent and highly selective inhibitors restraining endothelial cell proliferation in vitro by covalently binding to MetAP2. In order to further understand the unclear biological mechanisms and pharmacological processes of fumagillin and its derivatives, fumagillin-biotin conjugate 8 was designed and synthesized, which is linked with a 27-atom connection chain and by urethane (carbamate) bonds between fumagillol and D-norbiotinamine. The conjugate 8 shows comparable activity and selectivity against HUVEC proliferation as fumagillin. It was demonstrated that the conjugate 8 is stable inside the cell and its linker is of a suitable length for the detection of biotin in native and denatured conditions. Using the conjugate 8, it was determined that the cell permeability of fumagillin (1) and its analogs are not responsible for their inhibitory activity difference against the proliferation of endothelial and cancer cells. Furthermore, we confidently believe that our present strategy is a versatile and convenient method for investigating drug's cell permeability along with other studies regardless of reversible or irreversible interaction between the drug and binding target/s. PMID- 24211640 TI - Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction. AB - Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu2(PYP)2Cl4] (1), [Cu4(PYP)4(ClO4)2(H2O)2](ClO4)2.2H2O (2), and [Cu2(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC50 values ranging from 0.31 to 30.76 MUM. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL 7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA. PMID- 24211641 TI - An efficient approach to novel 17-5'-(1',2',4')-oxadiazolyl androstenes via the cyclodehydration of cytotoxic O-steroidacylamidoximes, and an evaluation of their inhibitory action on 17alpha-hydroxylase/C17,20-lyase. AB - Novel 17-exo-oxadiazoles in the androst-5-ene series were efficiently synthesized in a two-step sequence via the corresponding O-acylamidoxime intermediates (obtained from steroidal 17-carboxylic acids and amidoximes in the presence of coupling reagent), which then underwent tetrabutylammonium fluoride-induced cyclocondensation under mild reaction conditions. The synthesized compounds were subjected to in vitro pharmacological studies to investigate their inhibitory effect on rat testicular C17,20-lyase and their antiproliferative action on four malignant human adherent cell lines (HeLa, MCF7, A2780 and A431). One of the oxadiazolyl derivatives proved to exert significant enzyme-inhibitory action (IC50 = 0.60 MUM), while some of the isolated O-acylated amidoxime intermediates displayed high cytotoxic activities on all examined cell lines, with IC50 values in the range 0.22-3.94 MUM. PMID- 24211642 TI - Identification by in silico and in vitro screenings of small organic molecules acting as reversible inhibitors of kallikreins. AB - Netherton syndrome is caused by loss-of-function mutations in SPINK5 encoding the Kazal-type inhibitor LEKTI-1 leading to dysregulation of proteolytic cascades involving several kallikreins. We used both structure-based and ligand-based virtual screening computations to identify commercially available non-covalent inhibitors of human kallikrein 5 (hK5), a serine protease (trypsin-like) that plays a central role in the initiation of the molecular cascades leading to the Netherton syndrome phenotype. The efficacy and mechanism of inhibition of the identified new families of organic compounds were analyzed not only for hK5 but also on other proteases implicated in the cascades (hK7, hK14 and matriptase). These inhibitors are nontoxic on healthy human keratinocytes and are structurally different from traditional serine protease inhibitors validating their potential utility as initial hits to control proteolytic disorders observed in dermatological pathologies such as Netherton syndrome. PMID- 24211643 TI - HR-MAS NMR reveals a pH-dependent LPS alteration by de-O-acetylation at abequose in the O-antigen of Salmonella enterica serovar Typhimurium. AB - NMR spectroscopy can detect biomolecules like lipopolysaccharide directly on the surface of the cell, thus avoiding isolation and purification, and providing a more realistic description than the one derived from in vitro studies. Here we present a high-resolution magic-angle spinning NMR study of the O-antigen of Salmonella enterica serovar Typhimurium (S. Typhimurium) performed directly on the cells showing the alteration of its acetylation state over time. The O antigen region of S. Typhimurium consists of the repeating unit [->2)-alpha-d Manp-(1->4)-alpha-l-Rhap-(1->3)-alpha-d-Galp-(1->] where Man stands for mannose, Rha for rhamnose, and Gal for galactose. Man is substituted with abequose (Abe) O acetylated at carbon 2. Our studies revealed that the appearance of de-O acetylated O-antigen in the stationary growth phase is due to the de-O acetylation of already synthesized O-acetylated O-antigen and that this reaction is caused by the metabolism-induced basic pH of the growth medium. The labile O acetylation of the O-antigen we observed in S. Typhimurium generates non stoichiometric O-acetylation states and therefore changes the nature of an immunogenic epitope. PMID- 24211644 TI - Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology. AB - Copy number variations (CNVs) contribute to neuropsychiatric diseases, which may be partly mediated by their effects on gene expression. However, few studies have assessed the influence of CNVs on gene expression in the brain. The objective was to perform an unbiased comprehensive survey of influence of CNVs on gene expression in human brain tissues. CNV regions (CNVRs) were identified in 72 individuals (23 schizophrenia, 23 bipolar disorder and 26 controls). Significant associations between the CNVRs and gene expression levels were observed for 583 CNVR-expression probe pairs (293 unique eCNVRs and 429 unique transcripts), after corrections for multiple testing and controlling the effect of the number of subjects with CNVRs by label swapping permutations. These CNVRs affecting gene expression (eCNVRs) were significantly enriched for rare/low frequency (p=1.087*10(-10)) and gene-harboring CNVRs (p=1.4*10(-6)). Transcripts overlapping CNVRs were significantly enriched for glutathione metabolism and oxidative stress only for cases but not for controls. Moreover, 72 (24.6%) of eCNVRs were located within the chromosomal aberration regions implicated in psychiatric-disorders: 16p11.2, 1q21.1, 22q11.2, 3q29, 15q11.2, 17q12 and 16p13.1. These results shed light on the mechanism of how CNVs confer a risk for psychiatric disorders. PMID- 24211645 TI - Cellulose-inducible xylanase Xyl10A from Acremonium cellulolyticus: Purification, cloning and homologous expression. AB - Cellulose-inducible endo-beta-1,4-xylanase (Xyl10A) from the mesophilic fungus Acremonium cellulolyticus was purified, characterized, and expressed by a homologous expression system. A. cellulolyticus CF-2612 produces a high level of xylanase upon induction by Solka-Floc cellulose. To identify this xylanase, the major fraction showing xylanase activity was purified from the CF-2612 culture supernatant, and its gene was identified from the genome sequence. Amino acid sequence homology of Xyl10A revealed that the purified xylanase, designated Xyl10A, exhibited significant homology to family 10 of the glycoside hydrolases (GH10), possessing a cellulose-binding module 1 in the C-terminal region. The xyl10A gene was cloned and expressed in A. cellulolyticus under the control of a glucoamylase promoter. Two recombinant Xyl10As (rXyl10A-I, 53kDa, and rXyl10A-II, 51kDa) were purified that have slightly different molecular weights based on SDS PAGE. The rXyl10As had the same physicochemical and enzymatic properties as wtXyl10A: high thermostability (Tm 80.5 degrees C), optimum pH 5.0 and specific activity 232-251U/mg for birchwood xylan. The molecular weights of N deglycosylated rXyl10As were consistent with that of wild-type Xyl10A (wtXyl10A, 51kDa). PMID- 24211646 TI - Reduction of cell viability induced by IFN-alpha generates impaired data on antiviral assay using Hep-2C cells. AB - Type I interferons (IFNs) exert an array of important biological functions on the innate immune response and has become a useful tool in the treatment of various diseases. An increasing demand in the usage of recombinant IFNs, mainly due to the treatment of chronic hepatitis C infection, augmented the need of quality control for this biopharmaceutical. A traditional bioassay for IFN potency assessment is the cytopathic effect reduction antiviral assay where a given cell line is preserved by IFN from a lytic virus activity using the cell viability as a frequent measure of end point. However, type I IFNs induce other biological effects such as cell-cycle arrest and apoptosis that can influence directly on viability of many cell lines. Here, we standardized a cytopathic effect reduction antiviral assay using Hep-2C cell/mengovirus combination and studied a possible impact of cell viability variations caused by IFN-alpha 2b on responses generated on the antiviral assay. Using the four-parameter logistic model, we observed less correlation and less linearity on antiviral assay when responses from IFN-alpha 2b 1000 IU/ml were considered in the analysis. Cell viability tests with MTT revealed a clear cell growth inhibition of Hep-2C cells under stimulation with IFN-alpha 2b. Flow cytometric cell-cycle analysis and apoptosis assessment showed an increase of S+G2 phase and higher levels of apoptotic cells after treatment with IFN-alpha 2b 1000 IU/ml under our standardized antiviral assay procedure. Considering our studied dose range, we also observed strong STAT1 activation on Hep-2C cells after stimulation with the higher doses of IFN-alpha 2b. Our findings showed that the reduction of cell viability driven by IFN-alpha can cause a negative impact on antiviral assays. We assume that the cell death induction and the cell growth inhibition effect of IFNs should also be considered while employing antiviral assay protocols in a quality control routine and emphasizes the importance of new approaches for IFN potency determination. PMID- 24211647 TI - How do you diagnose appendicitis? An international evaluation of methods. AB - INTRODUCTION: Considerable variability exists in the diagnostic approach to acute appendicitis (in children), affecting both quality and costs of care. Interestingly, an international evaluation of what is commonly practiced today has not been performed. We aimed to document current practice patterns in the diagnosis of appendicitis in children and to determine whether a consensus exists in the workup of these patients among Canadian, Dutch, and Saudi Arabian pediatric surgeons. METHODS: We performed a cross-sectional survey using a pre designed, self-administered, 14-item survey. We sent the survey to participants via electronic mail. RESULTS: In total, 83 responses were received and analyzed, yielding a response rate of 42%. The majority of respondents practiced at pediatric surgery centers with over 50 beds (58% of Canadian surgeons, 81% of Dutch surgeons, 93% of Saudi Arabian surgeons). The majority of Dutch surgeons had a preference for physical examination and radiological imaging as opposed to Canadian and Saudi Arabian surgeons who favored history and physical examination. Interestingly, only one of the surgeons surveyed used an appendicitis scoring system. Regarding history and physical examination, most respondents deemed migratory abdominal pain and localized RLQ tenderness to be most suggestive of appendicitis. Ultrasound was the most preferable imaging modality in acute appendicitis across all three countries. CONCLUSION: This study demonstrates that international pediatric surgeons vary substantially in the diagnostic workup of patients with appendicitis. Furthermore, there is a variability between common practice and the current evidence. We recommend that pediatric surgeons develop clinical practice guidelines that are based on consensus information (expert opinion) and the best available literature. PMID- 24211648 TI - A 6-year-old girl with vaginal bleeding. PMID- 24211649 TI - Evaluation of hot-melt extrusion technique in the preparation of HPC matrices for prolonged release. AB - The aim of the work was to explore the potential of hot-melt extrusion (HME) for preparing hydroxypropyl cellulose (HPC)-based prolonged-release matrices intended for oral administration. For this purpose, compressed and extruded systems, either composed of polymer only or containing different amounts of a model drug (theophylline or ketoprofen), were compared. The overall morphological/physical changes of the systems following interaction with water indicated that the manufacturing process would not exert a major influence on the swelling behavior of the polymeric matrices. On the other hand, the release rate was generally higher from HME systems probably due to an increase of the drug dissolution rate, which is in agreement with the relevant DSC data (loss of drug cristallinity). However, the technological characteristics of the matrices and the maximum drug load were demonstrated to depend on the mode of interaction of the active ingredient with the molten polymer. In this respect, the formation of a composite material from ketoprofen and HPC, when mixed in specific ratios, was supposed to explain the differences observed between compressed and extruded systems in terms of morphological characteristics, hydration/swelling and release. The obtained results support the possibility of exploiting the advantages offered by HME technique, above all the potential for continuous manufacturing, in the preparation of prolonged-release swellable matrices based on a cellulose derivative. PMID- 24211650 TI - The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging. AB - The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications. PMID- 24211651 TI - Photothermal ablation of tumor cells using a single-walled carbon nanotube peptide composite. AB - Single-walled carbon nanotubes (SWCNTs) are known to have great potential for biomedical applications such as photothermal ablation of tumor cells in combination with near-infrared (NIR) irradiation. In this study, the photothermal activity of a novel SWCNTs composite with a designed peptide having a repeated structure of H-(-Lys-Phe-Lys-Ala-)7-OH [(KFKA)7] against tumor cells was evaluated in vitro and in vivo. The SWCNT-(KFKA)7 composite demonstrated high aqueous dispersibility that enabled SWCNTs to be used in tumor ablation. The NIR irradiation of SWCNT-(KFKA)7 solution resulted in a rapid temperature increase dependent on the SWCNTs concentration up to 50MUg/ml. Three minutes of NIR irradiation of a colon 26 or HepG2 cell culture incubated with SWCNT-(KFKA)7 resulted in remarkable cell damage, while that by single treatment with SWCNT (KFKA)7 or NIR irradiation alone was moderate. The intratumoral injection of SWCNT-(KFKA)7 solution followed by NIR irradiation resulted in a rapid increase of the temperature to 43 degrees C in the subcutaneously inoculated colon 26 tumor based on thermographic observation and remarkable suppression of tumor growth compared with treatment with only SWCNT-(KFKA)7 injection alone or NIR irradiation alone. These results suggest the a great potential of an SWCNT peptide composite for use in photothermal cancer therapy. PMID- 24211652 TI - Valproate improves prepulse inhibition deficits induced by corticotropin releasing factor independent of GABA(A) and GABA(B) receptor activation. AB - Corticotropin-releasing factor (CRF) is implicated in the pathogenesis of bipolar disorder, an illness associated with deficits in prepulse inhibition (PPI) of the acoustic startle response. Valproate is used in the treatment of bipolar disorder and may alter CRF activity via a GABA(A)-ergic mechanism. This study determined the effect of valproate on CRF-disrupted PPI and examined the role of the hypothalamic-pituitary-adrenal axis and GABA-ergic signaling in the effect of valproate. Valproate (60-240 mg/kg) dose-dependently reversed PPI deficits displayed by transgenic mice overexpressing CRF (CRFtg), and normalized PPI deficits induced by CRF i.c.v. infusion in 129Sv mice. Valproate enhanced corticosterone secretion more effectively in CRFtg than in wild-type mice. The effect of valproate on PPI was not blocked by the GABA(A) receptor antagonist bicuculline, the GABA(B) receptor antagonists phaclofen and SCH 50911 or combined administration of a GABA(A) and GABA(B) receptor antagonist. The beneficial effect of valproate on PPI was not mimicked by the GABA(A) receptor agonist muscimol, the GABA transaminase inhibitor vigabatrin, the histone deacetylase (HDAC) inhibitor sodium butyrate or by the mood stabilizers lithium, carbamazepine, lamotrigine or topiramate. Thus, we showed that valproate improves CRF-induced PPI deficits, albeit via a so far unknown mechanism. These marked beneficial effects of valproate on CRF-induced sensorimotor gating deficits suggest that valproate may be of particular value in specific subgroups of bipolar patients that are characterized by alterations in the CRF system. PMID- 24211653 TI - Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action. AB - The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neurons projecting to ventral tegmental area express 5-HT2A receptors suggesting that atypical antipsychotic drugs modulate dopaminergic activity distally, via 5-HT2A receptor (5-HT2A-R) blockade in PFC. Since the mPFC also projects heavily to NAc, we examined whether NAc-projecting pyramidal neurons also express 5-HT2A-R. Using a combination of retrograde tracing experiments and in situ hybridization we report that a substantial proportion of mPFC-NAc pyramidal neurons in rat brain express 5-HT2A-R mRNA in a layer- and area-specific manner (up to 68% in layer V of contralateral cingulate). The functional relevance of 5-HT2A-R to modulate mPFC-NAc projections was examined in dual-probe microdialysis experiments. The application of the preferential 5-HT2A R agonist DOI into mPFC enhanced glutamate release locally (+66 +/- 18%) and in NAc (+74 +/- 12%) indicating that cortical 5-HT2A-R activation augments glutamatergic transmission in NAc. Since NAc integrates glutamatergic and dopaminergic inputs, blockade of 5-HT2A-R by atypical drugs may reduce cortical excitatory inputs onto GABAergic neurons of NAc, adding to dopamine D2 receptor blockade. Together with previous observations, the present results suggest that atypical antipsychotic drugs may control the activity of the mesolimbic pathway at cell body and terminal level. PMID- 24211654 TI - Visual search and attention to faces during early infancy. AB - Newborn babies look preferentially at faces and face-like displays, yet over the course of their first year much changes about both the way infants process visual stimuli and how they allocate their attention to the social world. Despite this initial preference for faces in restricted contexts, the amount that infants look at faces increases considerably during the first year. Is this development related to changes in attentional orienting abilities? We explored this possibility by showing 3-, 6-, and 9-month-olds engaging animated and live-action videos of social stimuli and also measuring their visual search performance with both moving and static search displays. Replicating previous findings, looking at faces increased with age; in addition, the amount of looking at faces was strongly related to the youngest infants' performance in visual search. These results suggest that infants' attentional abilities may be an important factor in facilitating their social attention early in development. PMID- 24211655 TI - A Pou5f1/Oct4 dependent Klf2a, Klf2b, and Klf17 regulatory sub-network contributes to EVL and ectoderm development during zebrafish embryogenesis. AB - In mammalian ES cells, the transcription factors Klf4 and Klf2 contribute to maintenance of pluripotency and self-renewal and are regulated by Pou5f1/Oct4. In the early zebrafish embryo Pou5f1/Oct4 is necessary for expression of three Klf2/4 family members, klf2a, klf2b and klf17 (previously klf4b), similar to the regulation reported for mammalian ES cells. In this study, we analyzed blastula and gastrula stage Klf regulatory networks and their influence on zebrafish embryonic patterning. We show that Pou5f1 acts in combination with region specific factors to activate klf2a, klf2b, and klf17 in the superficial cell layer of the embryo. In addition, Pou5f1 acts together with the BMP signaling pathway to activate and maintain expression of klf2a and klf2b in a ventral ectodermal domain. We used microarray expression profiles of klf2a, klf2b and klf17 knockdown and overexpression embryos to identify Klf target genes, which reveals that Klfs participate in specification of the extraembryonic enveloping layer (EVL). We discuss mechanistic implications of simultaneous activation of transcriptional targets by ubiquitous, like Pou5f1, and region-specific inducers, emerging as a common regulatory motif in early development. PMID- 24211656 TI - Evidence of an alternative oxidase pathway for mitochondrial respiration in the scuticociliate Philasterides dicentrarchi. AB - The presence of an alternative oxidase (AOX) in the mitochondria of the scuticociliate P. dicentrarchi was investigated. The mitochondrial oxygen consumption was measured in the presence of KCN, an inhibitor of cytochrome pathway (CP) respiration and salicylhydroxamic acid (SHAM), a specific inhibitor of alternative pathway (AP) respiration. AOX expression was monitored by western blotting with an AOX polyclonal antibody. The results showed that P. dicentrarchi possesses a branched mitochondrial electron transport chain with both cyanide sensitive and -insensitive oxygen consumption. Mitochondrial respiration was partially inhibited by cyanide and completely inhibited by the combination of cyanide and SHAM, which is direct evidence for the existence of an AP in this ciliate. SHAM significantly inhibited in vitro growth of trophozoites both under normoxic and hypoxic conditions. AOX is a 42kD monomeric protein inducible by hypoxic conditions in experimental infections and by CP inhibitors such as cyanide and antimycin A, or by AP inhibitors such as SHAM. CP respiration was greatly stimulated during the exponential growth phase, while AP respiration increased during the stationary phase, in which AOX expression is induced. As the host does not possess AOX, and because during infection P. dicentrarchi respires via AP, it may be possible to develop inhibitors targeting the AP as a novel anti scuticociliate therapy. PMID- 24211657 TI - Microparticles of Aloe vera/vitamin E/chitosan: microscopic, a nuclear imaging and an in vivo test analysis for burn treatment. AB - The use of drug-loaded nanoparticles and microparticles has been increasing, especially for cosmetic and drug delivery purposes. In this work, a new microparticle formulation was developed for use in the healing process of skin burns in a composition of Aloe vera/vitamin E/chitosan. In order to observe the morphological properties, Raman and atomic force microscopy evaluation were performed. The biodistribution studies were analyzed by using a nuclear methodology, labeling the microparticles with Technetium-99m and in vivo test was procedure to analyzed the cicatrization process. The results of AFM analysis show the formation and the adherence property of the microparticles. Raman analyses show the distribution of each component in the microparticle. The nuclear method used shows that the biodistribution of the microparticles remained in the skin. The in vivo cicatrization test showed that the poloxamer gel containing the microparticles make a better cicatrization in relation to the other formulations tested. PMID- 24211658 TI - Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. AB - Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. PMID- 24211659 TI - Selective vulnerability of hippocampal sub-fields to oxygen-glucose deprivation is a function of animal age. AB - For more than a century, the hippocampal sub-fields have been recognized as being differentially vulnerable to injury. While the cause remains unknown, the explanations generally considered have involved either vascular differences, or innate variability among cells. To examine the latter possibility, we prepared acute hippocampal slices from Sprague-Dawley rats, applied a brief period of oxygen-glucose deprivation (OGD; an in vitro model of ischemia), and assessed the viability of dissected sub-fields (CA1, CA3, dentate gyrus) by measuring mitochondrial 2,3,5-triphenyltetrazolium chloride (TTC) metabolism. In slices from young animals (15 weeks of age), post-OGD TTC metabolism was significantly reduced in the CA sub-fields relative to the dentate gyrus. Since previous studies found increasing age may worsen ischemic injury, we completed the same experiment using tissue from animals at 52 weeks of age, and found no differences in TTC metabolism across sub-fields. Given the established role of glutamate receptors in ischemic cell death, we examined two key subunit proteins (GluN1, found in all NMDA receptors, and GluA2, found in most AMPA receptors) across sub fields and age to determine whether their expression complemented our viability data. We found that, relative to the CA1, the DG displayed greater GluN1 expression and lower GluA2 expression in both young and old animals. Our results confirm that regional vulnerability can be shown in a slice model, that the property is not intransigent, and that these features are likely not attributable to the expression pattern of key glutamate receptor subunits, but another molecular variable that changes over the lifespan. PMID- 24211660 TI - Screening and identification of dynamin-1 interacting proteins in rat brain synaptosomes. AB - Dynamin-1 is a multi-domain GTPase that is crucial for the fission stage of synaptic vesicle recycling and vesicle trafficking. In this study, we constructed prokaryotic expression plasmids for the four functional domains of dynamin-1, which are pGEX-4T-2-PH, pGEX-4T-2-PRD, pGEX-4T-2-GED and pGEX-4T-2-GTPase. Glutathione S-transferase pull-down, co-immunoprecipitation (co-IP), and liquid chromatography/mass spectrometry were used to screen and identify dynamin-1 interacting proteins in rat brain synaptosomes. We identified a set of 63 candidate protein interactions, including 36 proteins interacting with dynamin-1 C-terminal proline-rich domain (PRD), 14 with pleckstrin-homology domain (PH), 7 with GTPase effector domain (GED) and 6 with GTPase domain, consisting of synaptic vesicle-associated proteins, cytoskeletal proteins, metabolic enzymes and other proteins. We selected three previously unreported dynamin-1 interacting proteins to verify their interaction with dynamin-1 under native conditions. Using co-IP, we found that Rab GDP-dissociation inhibitor (Rab GDI) and chloride channel 3 (ClC-3) do interact with dynamin-1, but not with TUC-4b (the TOAD 64/Ulip/CRMP (TUC) family member). Those novel interactions detected in our study offer valuable insight into the protein-protein interacting network that could enhance our understanding of dynamin-1 mediated synaptic vesicle recycling. PMID- 24211661 TI - Cerebro-fronto-facial syndrome type 3 with polymicrogyria: a clinical presentation of Baraitser-Winter syndrome. AB - Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum. PMID- 24211662 TI - Investigation of the effects of process variables on derived properties of spray dried solid-dispersions using polymer based response surface model and ensemble artificial neural network models. AB - The objective of this study was to use different statistical tools to understand and optimize the spray drying process to prepare solid dispersions. In this study we investigated the relationship between input variables (inlet temperature, feed concentration, flow rate, solvent and atomization parameters) and quality attributes (yield, outlet temperature and mean particle size) of spray dried solid dispersions (SSDs) using response surface model and ensemble artificial neural network. The Box Behnken design was developed to investigate the effect of various input variables on quality attributes of final products. Moreover, Pearson correlation analysis, self organizing map, contour plots and response surface plot were used to illustrate the relationship between input variables and quality attributes. The influence of different physicochemical properties of solvent on the quality attributes of spray dried products was also investigated. Final validation of prepared models was done using binary SSDs of six model drugs with PVP. Results demonstrated the effectiveness of proposed PVP based model which can help scientists to gain detailed understanding of spray drying process of solid dispersion using minimal resources and time during early formulation development stage. It will also help them to ensure consistent quality of SSDs using broad range of input variables. PMID- 24211663 TI - Antisense oligonucleotides on neurobehavior, respiratory, and cardiovascular function, and hERG channel current studies. AB - INTRODUCTION: Safety Pharmacology studies were conducted in mouse, rat, and non human primate to determine in vivo effects of antisense oligonucleotides (ASOs) on the central nervous system, respiratory system, and cardiovascular system. Effects on the hERG potassium channel current was evaluated in vitro. METHODS: ASOs contained terminal 2'-O-methoxyethyl nucleotides, central deoxy nucleotides, and a phosphorothioate backbone. Neurobehavior was evaluated by Functional Observatory Battery in rodents. Respiratory function was directly measured in rodents by plethysmograph; respiratory rate and blood gases were measured in monkey. Basic cardiovascular endpoints were measured in rat; cardiovascular evaluation in monkey involved implanted telemetry units. In single and repeat dose studies ASOs were administered by subcutaneous injection at up to 300 mg/kg, 250 mg/kg, and 40 mg/kg in mouse, rat, or monkey, respectively. Assays were performed in HEK293 or CHO-K1 cells, stably transfected with hERG cDNA, at ASO concentrations of up to 300 MUM. RESULTS: No apparent effects were noted for respiratory or CNS function. Continuous monitoring of the cardiovascular system in monkey demonstrated no ASO-related changes in blood pressures, heart rate, or ECG and associated parameters (i.e., QRS duration). Specific assessment of the hERG potassium channel indicated no potential for actions on ventricular repolarization or modest effects only at excessive concentrations. DISCUSSION: The absence of direct actions on neurobehavior and respiratory function associated with the administration of ASOs in safety pharmacology core battery studies is consistent with published toxicology studies. The combination of in vitro hERG studies and in vivo studies in rat and monkey are consistent with no direct actions by ASOs on cardiac cell function or electrical conduction at relevant concentrations and dose levels. Taken as a whole, dedicated studies focused on the safety pharmacology of specific organ systems do not appear to add significant data for interpretation of potential adverse effects. The need for dedicated studies for future ASOs in the same class is questionable, as a more encompassing data set can be collected in repeat dose and longer-term toxicology studies. PMID- 24211665 TI - The challenges of classical swine fever control: modified live and E2 subunit vaccines. AB - Classical swine fever (CSF) is an economically important, highly contagious disease of swine worldwide. CSF is caused by classical swine fever virus (CSFV), and domestic pigs and wild boars are its only natural hosts. The two main strategies used to control CSF epidemic are systematic prophylactic vaccination and a non-vaccination stamping-out policy. This review compares the protective efficacy of the routinely used modified live vaccine (MLV) and E2 subunit vaccines and summarizes the factors that influence the efficacy of the vaccines and the challenges that both vaccines face to CSF control. Although MLV provide earlier and more complete protection than E2 subunit vaccines, it has the drawback of not allowing differentiation between infected and vaccinated animals (DIVA). The marker vaccine of E2 protein with companion discriminatory test to detect antibodies against E(rns) allows DIVA and is a promising strategy for future control and eradication of CSF. Maternal derived antibody (MDA) is the critical factor in impairing the efficacy of both MLV and E2 subunit vaccines, so the well-designed vaccination programs of sows and piglets should be considered together. Because of the antigen variation among various genotypes of CSFV, antibodies raised by either MLV or subunit vaccine neutralize genotypically homologous strains better than heterologous ones. However, although this is not a major concern for MLV as the induced immune responses can protect pigs against the challenge of various genotypes of CSFVs, it is critical for E2 subunit vaccines. It is thus necessary to evaluate whether the E2 subunit vaccine can completely protect against the current prevalent strains in the field. An ideal new generation of vaccine should be able to maintain the high protective efficiency of MLV and overcome the problem of antigenic variations while allowing for DIVA. PMID- 24211664 TI - Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection. AB - The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 10(7.2) TCID50 of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjunctival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV. PMID- 24211666 TI - The 5' untranslated region of Bean pod mottle virus RNA2 tolerates unusually large deletions or insertions. AB - Bean pod mottle virus (BPMV) is a bipartite, positive-sense (+) RNA virus of Secoviridae. We recently reported that a 137 nucleotide (nt) stretch (#263-399) of the 466 nt 5' untranslated region (5' UTR) of BPMV RNA2 can be deleted without compromising BPMV propagation in host plants [Lin et al., J. Gen. Virol. 94 (2013) 1415-1420]. Here we demonstrate that nonviral insertions of up to 625 nt is tolerated by the same region. Furthermore, one insertion mutant underwent recombination in infected plants, leading to the truncation of nt #250-361, thus extending the dispensable sequence to 150 nt (nt #250-399). We are unaware of any other (+) RNA virus that tolerates insertion/deletion of these sizes (625 nt/150 nt) within its 5' UTR. Importantly, tolerance of large insertions within the RNA2 5' UTR offers a novel, more convenient site for incorporating host gene fragments, making BPMV a more versatile vector of virus-induced gene silencing. PMID- 24211667 TI - Involvement of HSC70-4 and other inducible HSPs in Bombyx mori nucleopolyhedrovirus infection. AB - Heat shock proteins (HSPs) and heat shock cognate proteins (HSCs) function as molecular chaperones under normal cellular conditions. In this report, we describe the role of Bombyx mori heat shock cognate protein 70-4 (BmHSC70-4), which is a constitutively expressed member of the heat shock protein 70 (HSP70) family, in B. mori nucleopolyhedrovirus (BmNPV) infection. We first generated the BmHSC70-4 antibody, which can react specifically with an endogenous BmHSC70 from BmN cells. Immunohistochemistry has demonstrated that BmHSC70-4 was expressed at steady-state levels throughout the BmNPV infection and was accumulated in the nucleus of BmNPV-infected cells at a very late phase of infection. Western blot experiments have also shown that BmHSC70-4 is a novel component protein of budded virus (BV) and occlusion-derived virus (ODV). Next, we investigated the effect of KNK437, a known inhibitor of inducible HSPs, in BmNPV-infected BmN cells and found that both reduced BV production and delayed viral DNA replication were observed in virus-infected cells treated with KNK437. Furthermore, the formation of occlusion bodies (OBs) was not observed in KNK437-treated cells because this compound reduced the promoter activity of the polyhedrin gene severely. Collectively, the present results suggest that BmHSC70-4 is a novel structural protein of BmNPV and may have important roles in BmNPV propagation. PMID- 24211669 TI - Carbon nanotubes in medicine and biology - safety and toxicology. PMID- 24211668 TI - A novel pyrosequencing assay for the detection of neuraminidase inhibitor resistance-conferring mutations among clinical isolates of avian H7N9 influenza virus. AB - A novel reassortant avian influenza A virus (H7N9) emerged in humans in Eastern China in late February 2013. All virus strains were resistant to adamantanes (amantadine and rimantadine), but susceptible to neuraminidase inhibitors (NAIs) (oseltamivir and zanamivir). One strain (A/shanghai/1/2013) contained the R294K substitution in the neuraminidase (NA) gene, indicating resistance to oseltamivir. Pyrosequencing has proven to be a useful tool in the surveillance of drug resistance in influenza A viruses. Here, we describe a reverse transcription (RT)-PCR assay coupled with pyrosequencing to identify the NA residues E120, H276, and R294 (N9 numbering) of H7N9 viruses. A total of 43 specimens (26 clinical samples and 17 isolates) were tested. Only one isolate containing the E120V heterogenic mutation was detected by pyrosequencing and confirmed by Sanger sequencing. However, this mutation was not detected in the original clinical specimen. Since virus isolation might lead to the selection of variants that might not fully represent the virus population in the clinical specimens, we suggest that using pyrosequencing to detect NAI resistance in H7N9 viruses directly from clinical specimens rather than from cultured isolates. No cross reactions with other types of influenza virus and respiratory tract viruses were found, and this assay has a sensitivity of 100 copies of synthetic RNA for all three codons. The high sensitivity and specificity of the assay should be sufficient for the detection of positive clinical specimens. In this study, we provide a rapid and reliable method for the characterization of NAI resistance in H7N9 viruses. PMID- 24211670 TI - The influence of human physical activity and contaminated clothing type on particle resuspension. AB - A study was conducted to experimentally quantify the influence of three variables on the level of resuspension of hazardous aerosol particles from clothing. Variables investigated include physical activity level (two levels, low and high), surface type (four different clothing material types), and time i.e. the rate at which particles resuspend. A mixture of three monodisperse tracer labelled powders, with median diameters of 3, 5, and 10 microns, was used to "contaminate" the samples, and the resuspended particles were analysed in real time using an Aerodynamic Particle Sizer (APS), and also by Neutron Activation Analysis (NAA). The overall finding was that physical activity resulted in up to 67% of the contamination deposited on clothing being resuspended back into the air. A detailed examination of the influence of physical activity level on resuspension, from NAA, revealed that the average resuspended fraction (RF) of particles at low physical activity was 28 +/- 8%, and at high physical activity was 30 +/- 7%, while the APS data revealed a tenfold increase in the cumulative mass of airborne particles during high physical activity in comparison to that during low physical activity. The results also suggest that it is not the contaminated clothing's fibre type which influences particle resuspension, but the material's weave pattern (and hence the material's surface texture). Investigation of the time variation in resuspended particle concentrations indicated that the data were separable into two distinct regimes: the first (occurring within the first 1.5 min) having a high, positive rate of change of airborne particle concentration relative to the second regime. The second regime revealed a slower rate of change of particle concentration and remained relatively unchanged for the remainder of each resuspension event. PMID- 24211671 TI - Source term estimation of radioxenon released from the Fukushima Dai-ichi nuclear reactors using measured air concentrations and atmospheric transport modeling. AB - Systems designed to monitor airborne radionuclides released from underground nuclear explosions detected radioactive fallout across the northern hemisphere resulting from the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. Sampling data from multiple International Modeling System locations are combined with atmospheric transport modeling to estimate the magnitude and time sequence of releases of (133)Xe. Modeled dilution factors at five different detection locations were combined with 57 atmospheric concentration measurements of (133)Xe taken from March 18 to March 23 to estimate the source term. This analysis suggests that 92% of the 1.24 * 10(19) Bq of (133)Xe present in the three operating reactors at the time of the earthquake was released to the atmosphere over a 3 d period. An uncertainty analysis bounds the release estimates to 54 129% of available (133)Xe inventory. PMID- 24211672 TI - Novel features for identifying A-minors in three-dimensional RNA molecules. AB - RNA tertiary interactions or tertiary motifs are conserved structural patterns formed by pairwise interactions between nucleotides. They include base-pairing, base-stacking, and base-phosphate interactions. A-minor motifs are the most common tertiary interactions in the large ribosomal subunit. The A-minor motif is a nucleotide triple in which minor groove edges of an adenine base are inserted into the minor groove of neighboring helices, leading to interaction with a stabilizing base pair. We propose here novel features for identifying and predicting A-minor motifs in a given three-dimensional RNA molecule. By utilizing the features together with machine learning algorithms including random forests and support vector machines, we show experimentally that our approach is capable of predicting A-minor motifs in the given RNA molecule effectively, demonstrating the usefulness of the proposed approach. The techniques developed from this work will be useful for molecular biologists and biochemists to analyze RNA tertiary motifs, specifically A-minor interactions. PMID- 24211673 TI - Correlation between "Candidatus Liberibacter solanacearum" infection levels and fecundity in its psyllid vector. AB - The potato/tomato psyllid, Bactericera cockerelli (Sulc) transmits the bacterium, "Candidatus (Ca.) Liberibacter solanacearum" (Lso), also known as "Ca. Liberibacter psyllaurous", which causes zebra chip disease in potato and other solanaceous crops. The authors previously showed that fecundity and nymph survival is significantly reduced in Lso-infected psyllids compared to uninfected psyllids on tomato. However, it is not known whether the level of the pathogen is correlated with concomitant reduction in fitness of the psyllid vector. Using quantitative PCR assays, Lso levels were determined in adult female founders of isofemale lines for whom several life history traits were previously recorded. Analysis of psyllid isofemale lines revealed that Lso infection levels in founders or mothers was negatively correlated with 7-day fecundity, nymph survival percentage, and number of F1 progeny including eggs, nymphs and adults. There was a significant negative density-dependent relationship between Lso level and fecundity. That is, psyllids experienced decreasing levels in fecundity with increasing bacterial titer. There was no apparent negative density-dependent relationship between Lso copies and number of nymphs, nymph survival percentage and number of adults. The negative effect of Lso on psyllid fecundity is likely due to direct effects of the bacteria on the insect host and not via the host plant. Taken together, these findings suggest that the level of Lso in its psyllid vector correlates with reduction in psyllid fitness. PMID- 24211674 TI - Digital gene expression analysis in the midgut of 4008 silkworm strain infected with cytoplasmic polyhedrosis virus. AB - Digital Gene Expression was performed to investigate the midgut transcriptome profile of 4008 silkworm strain orally infected with BmCPV. A total of 4,498,263 and 4,258,240 clean tags were obtained from the control and BmCPV-infected larvae. A total of 752 differentially expressed genes were detected, of which 649 were upregulated and 103 were downregulated. Analysis results of the Kyoto Encyclopedia of Genes and Genomes pathway showed that 334 genes were involved in the ribosome and RNA transport pathways. Moreover, 408 of the 752 differentially expressed genes have a GO category and can be categorized into 41 functional groups according to molecular function, cellular component and biological process. Differentially expressed genes involved in signaling, gene expression, metabolic process, cell death, binding, and catalytic activity changes were detected in the expression profiles. Quantitative real-time PCR was performed to verify the expression of these genes. The upregulated expression levels of Calreticulin, FK506-binding protein, and protein kinase c inhibitor gene probably led to a calcium-dependent apoptosis in the BmCPV-infected cells. The results of this study may serve as a basis for future research not only on the molecular mechanism of BmCPV invasion but also on the anti-BmCPV mechanism of silkworm. PMID- 24211675 TI - Effects of probucol, a typical hERG expression inhibitor, on in vivo QT interval prolongation in conscious dogs. AB - The cholesterol-lowering drug, probucol, is known to induce QT interval prolongation and torsades de pointes in patients. Recent in vitro studies have indicated that probucol reduces hERG expression in the plasma membrane and does not directly block human ether-a-go-go-related gene (hERG) channels. The present study was performed to investigate the effects of probucol on in vivo QT interval prolongation. Epicardial electrocardiograms were recorded in conscious dogs given oral single or repeated (7 days) doses of probucol (100mg/kg), and in combination with moxifloxacin (20mg/kg). QTc intervals were analyzed by a probabilistic method with individual rate collection formulae. Values of change in QTc (QTc) interval and its integration from 1 to 21 h (AUC1-21h) were calculated to evaluate drug-induced QT prolongation. A single dose of probucol slightly but significantly increased the AUC1-21h QTc interval on days 2 and 3. The QT prolongation was markedly augmented by repeated doses of probucol in a time-dependent manner, despite the lack of increase in plasma concentration. The combination of probucol and moxifloxacin produced additive effects on QT interval prolongation. These results suggest that long-term exposure to the hERG expression inhibitor, probucol, is required to evaluate its maximal effects on in vivo QT interval prolongation. A combination of direct and indirect hERG inhibitors may produce simple additive effects on QT interval prolongation. PMID- 24211677 TI - Vernakalant is devoid of proarrhythmic effects in the complete AV block dog model. AB - The anesthetized chronic AV-blocked dog (cAVB) and methoxamine-sensitized rabbit model are widely used to determine pro-arrhythmic properties of drugs. In general, both models show similar results. However, conflicting data have also been reported; K201 and AZD1305 induced Torsade de Pointes (TdP) exclusively in cAVB dogs. Vernakalant, an antiarrhythmic drug that blocks several ion channels has been approved only in Europe. Its propensity to induce repolarization dependent TdP arrhythmias has been evaluated solely in the methoxamine-sensitized rabbits. We therefore assessed the proarrhythmic potential of vernakalant in the cAVB dog model. Vernakalant was evaluated in 10 mongrel dogs (sinus rhythm (SR) 2mg/kg; chronic AV block (cAVB) 2+3mg/kg). The same dogs were challenged with dofetilide (25 MUg/kg) to evaluate TdP inducibility. During the serial experiments the animals were paced from the right ventricular apex (60 beats/min). Short-term variability of repolarization (STV) was quantified for proarrhythmic risk. In SR (n=8) vernakalant prolonged QT (265 +/- 11 to 311 +/- 18 ms P<0.01(**)) but not PQ or QRS. In cAVB (n=8), 2mg/kg vernakalant prolonged QT (391 +/- 43 to 519 +/- 73 ms(**)) and QRS (103 +/- 24 to 108 +/- 23 ms(**)). After a 30 min lag-time, 3mg/kg vernakalant (n=4) increased QT to a lesser extent (413 +/- 34 to 454 +/- 27 ms(**)) while maintaining QRS prolongation (114 +/- 18 to 122 +/- 20 ms(**)). Neither dose increased STV or caused arrhythmias. Dofetilide prolonged QT (398 +/- 51 to 615 +/- 71 ms(**)), increased STV (1.0 +/- 0.4 to 2.2 +/- 1.0 ms P<0.05(*)) and induced TdP arrhythmias in 6/8(*) cAVB dogs. Vernakalant did not induce arrhythmias in the cAVB dog model. Higher dosages (3mg/kg) did not prolong repolarization further whereas negative inotropic effects were starting to become apparent precluding further increases in dose. PMID- 24211676 TI - Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Huntington's disease like symptoms in rats: behavioral, biochemical, cellular and histological evidences. AB - Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Besides its anti-oxidant properties, the other probable mechanisms which underpin its neuroprotective potential are still not clear. In light of emerging role of flavonoids in modulating oxidative stress and neuro-inflammation, the study has been designed to explore the possible neuroprotective effect of hesperidin and its combination with minocycline (microglial inhibitor), against quinolinic acid (QA) induced Huntington's disease (HD) like symptoms in rats. Unilateral intrastriatal administration of QA (300 nmol/4 ul) significantly reduced body weight, impaired behavior (locomotor activity, beam balance and memory performance), caused oxidative damage (increased lipid peroxidation, nitrite concentration, depleted super oxide dismutase and reduced glutathione), demonstrated mitochondrial dysfunction (decreased Complex-I, II, III, and IV activities), increased striatal lesion volume and altered the levels of TNF-alpha, caspase-3 as well as BDNF expression, as compared to sham group. Meanwhile, chronic hesperidin (100mg/kg, p.o.) and minocycline (25mg/kg, p.o.) treatment for 21 days significantly attenuated the behavioral, biochemical and cellular alterations as compared to QA treated (control) animals, whereas hesperidin (50mg/kg, p.o.) treatment was found to be non-significant. However, treatment of hesperidin (50mg/kg) in combination with minocycline (25mg/kg) potentiated their neuroprotective effect, which was significant as compared to their effects per se in QA treated animals. Taken altogether, the results of the present study suggest a possible interplay of microglial modulation and anti-oxidant effect in neuroprotective potential of hesperidin against QA induced HD like symptoms in rats. PMID- 24211678 TI - Nausea and vomiting in advanced cancer. AB - Nausea and vomiting are very common symptoms in cancer both treatment and non treatment related. Many complications of advanced cancer such as gastroparesis, bowel and outlet obstructions, and brain tumors may have nausea and vomiting or either symptom alone. In a non-obstructed situation, nausea may be more difficult to manage and is more objectionable to patients. There is little research on management of these symptoms except the literature on chemotherapy induced nausea where guidelines exist. This article will review the etiologies of nausea and vomiting in advanced cancer and the medications which have been used to treat them. An etiology based protocol to approach the symptom is outlined. PMID- 24211679 TI - Mechanisms and clinical uses of capsaicin. AB - Capsaicin is the active ingredient of chili peppers and gives them the characteristic pungent flavor. Understanding the actions of capsaicin led to the discovery of its receptor, transient receptor potential vanilloid subfamily member 1 (TRPV1). This receptor is found on key sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been studied in animal and human models for various indications. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process known as defunctionalisation has been exploited for therapeutic use of capsaicin in various painful conditions. We reviewed different studies on mechanisms of action of capsaicin and its utility in different clinical conditions. A beneficial role of capsaicin has been reported in obesity, cardiovascular and gastrointestinal conditions, various cancers, neurogenic bladder, and dermatologic conditions. Various theories have been put forth to explain these effects. Interestingly many of these pharmacological actions are TRPV1 independent. This review is aimed at providing an overview of these mechanisms and to also present literature which contradicts the proposed beneficial effects of capsaicin. Most of the literature comes from animal studies and since many of these mechanisms are poorly understood, more investigation is required in human subjects. PMID- 24211680 TI - Combined analysis of cytokine gene polymorphism and the level of expression with allograft function in kidney transplant recipients. AB - Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL 17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total of 250 kidney transplant recipients were included in this study. Overall 70 recipients (28%) experienced an acute rejection. IL-17 197 A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/T gene polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 were also checked by ELISA. IL-17 GG carriers and G allele were significantly more frequent in patients with acute rejection as compared to patients without any sign of rejection (P=0.045 and P=0.032, respectively). In addition after gender classification, IL-23R AA carriers and A allele were significantly more frequent in male patients who experienced an acute rejection as compared to non-rejected patients (P=0.03, P=0.011, respectively). The IL-17 serum levels have also shown significant differences between rejected and non-rejected groups (24.37+/-32.94 for AR and 8.6+/-9.9 for non-AR groups, respectively; P=0.035). The mentioned results indicate that IL-17GG genotype, G allele and its serum level have predictive values for acute rejection. GG genotype and G allele of IL-17 is a genetic risk factor for development of acute rejection. Also, AA genotype and A allele of IL-23R is a sex dependent genetic risk factor for the development of acute rejection, but this subject needs to be studied in a different population. PMID- 24211681 TI - Evolution of learning strategies in temporally and spatially variable environments: a review of theory. AB - The theoretical literature from 1985 to the present on the evolution of learning strategies in variable environments is reviewed, with the focus on deterministic dynamical models that are amenable to local stability analysis, and on deterministic models yielding evolutionarily stable strategies. Individual learning, unbiased and biased social learning, mixed learning, and learning schedules are considered. A rapidly changing environment or frequent migration in a spatially heterogeneous environment favors individual learning over unbiased social learning. However, results are not so straightforward in the context of learning schedules or when biases in social learning are introduced. The three major methods of modeling temporal environmental change--coevolutionary, two timescale, and information decay--are compared and shown to sometimes yield contradictory results. The so-called Rogers' paradox is inherent in the two timescale method as originally applied to the evolution of pure strategies, but is often eliminated when the other methods are used. Moreover, Rogers' paradox is not observed for the mixed learning strategies and learning schedules that we review. We believe that further theoretical work is necessary on learning schedules and biased social learning, based on models that are logically consistent and empirically pertinent. PMID- 24211682 TI - Evolution of learning and levels of selection: a lesson from avian parent offspring communication. AB - In recent years, it has become increasingly clear that the evolution of behavior may be better understood as the evolution of the learning mechanisms that produce it, and that such mechanisms should be modeled and tested explicitly. However, this approach, which has recently been applied to animal foraging and decision making, has rarely been applied to the social and communicative behaviors that are likely to operate in complex social environments and be subject to multi level selection. Here we use genetic, agent-based evolutionary simulations to explore how learning mechanisms may evolve to adjust the level of nestling begging (offspring signaling of need), and to examine the possible consequences of this process for parent-offspring conflict and communication. In doing so, we also provide the first step-by-step dynamic model of parent-offspring communication. The results confirm several previous theoretical predictions and demonstrate three novel phenomena. First, negatively frequency-dependent group level selection can generate a stable polymorphism of learning strategies and parental responses. Second, while conventional reinforcement learning models fail to cope successfully with family dynamics at the nest, a newly developed learning model (incorporating behaviors that are consistent with recent experimental results on learning in nestling begging) produced effective learning, which evolved successfully. Third, while kin-selection affects the frequency of the different learning genes, its impact on begging slope and intensity was unexpectedly negligible, demonstrating that evolution is a complex process, and showing that the effect of kin-selection on behaviors that are shaped by learning may not be predicted by simple application of Hamilton's rule. PMID- 24211683 TI - Mitochondrial genomes of Anisakis simplex and Contracaecum osculatum (sensu stricto)--comparisons with selected nematodes. AB - Anisakid nematodes parasitize mainly fish, marine mammals and/or fish-eating birds, and can be transmitted to a range of fish-eating mammals, including humans, where they can cause gastrointestinal disease linked to larval infection or allergic responses. In spite of the animal and human health significance of these parasites, there are still gaps in our understanding of the systematics, biology, epidemiology and ecology of anisakids. Mitochondrial (mt) DNA provides useful genetic markers for investigations in these areas, but complete mt genomic data have been lacking for most anisakids. In the present study, the mt genomes of Anisakis simplex sensu stricto and Contracaecum osculatum sensu stricto were amplified from genomic DNA by long-range polymerase chain reaction and sequenced using 454 technology. The circular mt genomes of these species were 13,926 and 13,823 bp, respectively, and each of them contained 12 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes consistent for members of the Ascaridida, Oxyurida, Spirurida, Rhabditida and Strongylida. These mt genomes provide a stepping-stone for future comparative analyses of a range of anisakids and a basis for reinvestigating their genetic relationships. In addition, these markers might be used in prospecting for cryptic species and exploring host affiliations. PMID- 24211684 TI - Computational modelling of ALDH1B1 tetramer formation and the effect of coding variants. PMID- 24211685 TI - Emerging evidence for P body function in the peripheral nervous system. PMID- 24211686 TI - Altered source-based EEG coherence of resting-state sensorimotor network in early stage Alzheimer's disease compared to mild cognitive impairment. AB - Although the altered coherence between cortical areas in Alzheimer's disease (AD) has been widely studied, it remains unclear whether the source-based coherence measures within sensorimotor network show significant difference between mild cognitive impairment (MCI) and AD. In the present study, resting-state electroencephalographic signals were recorded from 21 MCI and 21 mild AD patients. The spectral power and coherence in the sensorimotor areas were analyzed using the minimum norm estimate (MNE) combined with fast Fourier transform and coherence analysis in delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-25 Hz), and gamma (25-40 Hz) bands. Our results indicated that source-based coherence in AD showed increased delta coherences between the bilateral precentral, left supplementary motor area (SMA) and right precentral, and left SMA and right postcentral areas. However, no significant difference of spectral powers was observed between AD and MCI. To conclude, the phenotype conversion from MCI to AD may be associated with an altered connectivity of the sensorimotor cortical network. This is a promising finding; however, further large-scale studies are needed. PMID- 24211687 TI - Oleuropein aglycone counteracts Abeta42 toxicity in the rat brain. AB - Previous data have shown that oleuropein aglycone (OLE), the main secoiridoid phenol present in extra virgin olive oil, counteracts in vitro aggregation of the Abeta42 peptide and protects cultured cells and model organisms against aggregates toxicity. In this study we investigated the relative tissue toxicity of Abeta42 aggregated in vitro in the presence or in the absence of OLE by injecting the nucleus basalis magnocellularis (NBM) of adult male Wistar rats with a 1.5 MUl solution containing OLE (450 MUM) or Abeta42 (50 MUM) aggregated in the absence (oligomers) or in the presence of 450 MUM OLE. Control rats were injected with vehicle (1.5 MUl). Thirty days after injection, the number of choline acetyltransferase (ChAT)-positive neurons, glia reaction and the Abeta peptide levels were detected by immunohistochemistry. An apparent reduction in the amount of soluble A11-positive oligomers was detected in the NBM injected with Abeta42 aggregated with OLE, as compared with the NBM injected with Abeta42 alone. In the latter case, the number of ChAT-positive neurons was significantly reduced (~-33%) respect to that recorded in the NBM injected with phosphate buffer, OLE or Abeta42 aggregated with OLE. A markedly attenuated Abeta-induced astrocytes and microglia reaction was also found in the NBM injected with Abeta42 aggregated with OLE. Altogether, these data provide additional support to the anti-aggregation, neuroprotective and anti-inflammatory activities of this natural phenol, confirming its beneficial properties against neurodegeneration. PMID- 24211688 TI - Effect of insulin-like growth factor-1 on corneal surface ultrastructure and nerve regeneration of rabbit eyes after laser in situ keratomileusis. AB - To explore the effect of insulin-like growth factor-1 (IGF-1) on corneal surface ultrastructure and nerve regeneration in rabbit models after laser in situ keratomileusis (LASIK). Forty-two healthy New Zealand white rabbits were divided into two groups, the IGF-1 group and the control group, and LASIK surgery was performed. The corneal surface ultrastructure was observed by transmission electron microscopy, and the nerve regeneration was evaluated by counting the newly regenerated nerves at 1 d, 1 w, 2 w, 1 m, 3 m and 6 m after surgery. Dry eye parameters, including the Schirmer I test and tear break-up time, were examined at all time points. The examination of corneal ultrastructure showed that the number of corneal epithelial microvilli in the IGF-1 group was significantly higher than that in the normal saline (NS) group except in the second postoperative week (p<0.05). The observation of corneal nerve regeneration showed that the number of regenerated nerve fibers in the IGF-1 group was higher than the control group at all time points (p<0.05). The parameters of dry eye were significantly higher in the IGF-1 group compared to the control group at all time points except at 1d and 6m after LASIK. IGF-1 can effectively accelerate the early repair of corneal surface ultrastructure and nerve regeneration after LASIK and relieve dry eye symptoms in rabbit eyes. PMID- 24211689 TI - Orexin type 1 receptor antagonism in Lateral Paragigantocellularis nucleus attenuates naloxone precipitated morphine withdrawal symptoms in rats. AB - Orexin neuropeptides have been reported to be involved in morphine induced physical dependence and withdrawal. The Lateral Paragigantocellularis (LPGi) is a key brain region implicated in the expression of somatic signs of morphine withdrawal syndrome. Orexin A and orexin type 1 receptor have been found in LPGi neurons but the effect of orexin on the expression of opiate dependence and withdrawal phenomena in this brain structure has not been studied yet. In this study, the effect of intra-LPGi administration of SB 334867 (selective orexin type 1 receptor antagonist) on the behavioral signs of morphine withdrawal syndrome was investigated. Male Wistar rats weighing 250-300 g were rendered dependent by adding morphine sulfate (Temad, Tehran, Iran) to their drinking water in increasing concentrations of 0.1, 0.2, 0.3mg/ml for every 48 h and 0.4 mg/ml during the next 15 days. Behavioral signs of morphine withdrawal were assessed in a transparent cylindrical Plexiglas test chamber (30 cm diameter, 50 cm height) for 25 min. One group of animals received intra-LPGi injection of SB 334867 (0.2 MUl, 100 MUM) immediately before naloxone. In the control group, SB 334867 vehicle (DMSO 1%, 0.2 MUl) was microinjected into LPGi. Our results indicate that intra-LPGi administration of SB 334867 significantly decreases naloxone precipitated morphine withdrawal signs. Thus, it seems that orexin might have a pivotal role in the expression of morphine withdrawal signs through affecting orexin type 1 receptor in LPGi nucleus. PMID- 24211690 TI - Protective effect of telmisartan against oxidative damage induced by high glucose in neuronal PC12 cell. AB - Telmisartan is an angiotensin II type 1 receptor blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma). Here, we investigated the protective capacity of telmisartan against high glucose (HG) elicited oxidative damage in PC12 cells. The activity of lactate dehydrogenase (LDH), NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT) as well as the levels of malondialdehyde (MDA), glutathione (GSH), intracellular reactive oxygen species (ROS), cell viability and DNA fragmentation were measured in HG treated PC12 cells with and without telmisartan co-treatment. Moreover, the direct antioxidant effect of telmisartan was determined by 2,2-azinobis-(3 ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay and protein expression of Bax, Bcl-2, cleaved caspase-3 and NOX subunit p47phox by western blotting. Telmisartan exhibited antioxidant activity in the ABTS assay with the IC50 value of 37.5 MUM. Pretreatment of PC12 cells with telmisartan, prior to HG exposure, was associated with a marked diminution in cleaved caspase-3 expression, DNA fragmentation, Bax/Bcl-2 ratio, intracellular ROS and MDA levels. Additionally, the cell viability, GSH level, SOD and CAT activity were notably elevated by telmisartan, whereas the activity and the protein expression of NADPH oxidase subunit p47phox were attenuated. Interestingly, co-treatment with GW9662, a PPAR gamma antagonist, partially inhibited the beneficial effects of telmisartan. These findings suggest that telmisartan has protective effects on HG-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action and inhibition of NADPH oxidase. Furthermore, the results show that PPAR-gamma activation is involved in the neuroprotective effects of telmisartan. PMID- 24211691 TI - SLC6A3 is a risk factor for Parkinson's disease: a meta-analysis of sixteen years' studies. AB - The human dopamine transporter gene (gene symbol: SLC6A3) is considered as a candidate risk factor for Parkinson's disease because dopamine transporter accumulates cytotoxic dopamine or other toxins in the dopamine neurons. However, findings from numerous association studies in different populations have been inconsistent with each other. In this study, we performed a combined analysis of published case-control genetic association data between SLC6A3 and Parkinson's disease. The results indicate that SLC6A3 confers a modest but significant risk for Parkinson's disease in various populations. Allele 10-repeat of the 40-base pair variable number tandem repeat, a well studied polymorphism in the 3' untranslated region of SLC6A3, confers neuroprotection in East Asian (OR: 0.78, 95% CI: 0.65, 0.94 and p=0.009) but not in Caucasian populations. Genotype GG and allele G of the promoter single nucleotide polymorphism rs2652510 is associated with a risk in Caucasians (allelic G, OR: 1.26, 95% CI: 1.04-1.54, and p=0.018; genotypic GG OR: 1.37, 95% CI: 1.03-1.84 and p=0.032). Such information implies a population-dependent involvement of SLC6A3 in the etiology of Parkinson's disease. PMID- 24211692 TI - Androgen regulates development of the sexually dimorphic gastrin-releasing peptide neuron system in the lumbar spinal cord: evidence from a mouse line lacking androgen receptor in the nervous system. AB - Androgens including testosterone, organize the nervous system as well as masculine external and internal genitalia during the perinatal period. Androgen organization involves promotion of masculine body features, usually by acting through androgen receptors (ARs). We have recently demonstrated that the gastrin releasing peptide (GRP) system in the lumbar spinal cord also mediates spinal centers promoting penile reflexes during male sexual behavior in rats. Testosterone may induce sexual differentiation of this spinal GRP system during development and maintain its activation in adulthood. In the present study, we examined the role of ARs in the nervous system regulating the development of the sexually dimorphic GRP system. For this purpose, we used a conditional mouse line selectively lacking the AR gene in the nervous system. AR floxed males carrying (mutants) or not (controls) the nestin-Cre transgene were castrated in adulthood and supplemented with physiological amounts of testosterone. Loss of AR expression in the nervous system resulted in a significant decrease in the number of GRP neurons compared to control littermates. Consequently, the intensity of GRP axonal projections onto the lower lumbar and upper sacral spinal cord was greater in control males than in mutant males. These results suggest that ARs expressed in the nervous system play a significant role in the development of the GRP system in the male lumbar spinal cord. The AR-deletion mutation may attenuate sexual behavior and activity of mutant males via spinal GRP system-mediated neural mechanisms. PMID- 24211693 TI - Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease. AB - The aging-suppressor gene klotho encodes a single-pass transmembrane protein that is predominantly secreted by the choroid plexus of the brain and in the kidney. Klotho-deficient mice develop multiple aging phenotypes, including impaired cognition. Klotho concentrations have not been described in the CSF of humans. We measured klotho in the CSF of 20 older adults with Alzheimer's disease and in 20 older and 20 younger adults with normal cognition. In 10 adults, aged 38-87 years, CSF klotho measurements were made at baseline and every 6h up to 18-30 h later. Mean (95% confidence interval [C.I.]) CSF klotho in men versus women were 899 (814, 983) and 716 (632, 801) pg/mL, respectively (P=0.002). Mean (95% C.I.) CSF klotho in older adults with and without Alzheimer's disease were 664 (603, 725) and 776 (705, 828) pg/mL, respectively (P=0.02), adjusting for sex. Mean (95% C.I.) klotho in older versus younger adults were 766 (658, 874) and 992 (884, 1100) pg/mL, respectively (P=0.005), adjusting for sex. In the longitudinal study of CSF klotho, no significant circadian fluctuations were found in CSF klotho levels. This study suggests that CSF klotho concentrations are lower in females compared with males, in Alzheimer's disease, and in older versus younger adults. PMID- 24211694 TI - Possession of bed nets in Haut-Katanga (DRC): prevalence-elastic behaviour or performance of health care system delivery? AB - This article provides an empirical multi-disciplinary strategy that enables to identify prevalence-elastic behaviours influencing the possession of mosquito nets and to assess the relative performance of health centers in promoting the possession of nets in Democratic Republic of Congo (DRC). We use a household survey conducted in 2009 in Haut Katanga, DRC. We combine these data with estimates on malaria prevalence from the Malaria Atlas project. Results show that households behave rationally with respect to the disease, meaning that the cause for a low possession of nets should be found elsewhere. They also show that health centers are not the most effective in promoting possession of bed nets, in areas where they are most needed for malaria control. PMID- 24211695 TI - Disparities in wheelchair procurement by payer among people with spinal cord injury. AB - OBJECTIVE: To identify insurance provider-related disparities in the receipt of lightweight, customizable manual wheelchairs or power wheelchairs with programmable controls among community-dwelling people with spinal cord injury (SCI). SETTING: Six Spinal Cord Injury Model System centers. DESIGN: A multicenter cross-sectional study. PARTICIPANTS: A total of 359 individuals at least 16 years of age or older and 1 year after SCI who use a manual or power wheelchair as their primary means of mobility. The subjects were stratified by payer, and payers were grouped according to reimbursement characteristics as follows: Medicaid/Department of Vocational Rehabilitation (DVR), private/prepaid, Medicare, Worker's Compensation (WC)/Veterans Affairs (VA), and self pay. METHODS: Demographic, wheelchair, and payer data were collected by medical record review and face-to-face interview. RESULTS: There were 125 participants in the Medicaid/DVR group, 120 in the private/prepaid group, 55 in the Medicare group, 30 in the WC/VA group, and 29 in the self-pay group. For manual wheelchair users, the likelihood of having a lightweight, customizable wheelchair was 97.5% for private/prepaid, 96.3% for Medicaid/DVR, 94.1% for WC/VA, 87.5% for Medicare, and 82.6% for self pay. For power wheelchair users, those with WC/VA (100%) were most likely to receive a customizable power wheelchair with programmable controls, followed by private/prepaid (95.1%), Medicaid/DVR (86.0 %), Medicare (83.9%), and self pay (50.0%). CONCLUSIONS: The only payer group for which all beneficiaries received wheelchairs that met standard of care were power wheelchairs provided by WC/VA. Fewer than 90% of people whose manual wheelchair was paid for by Medicare and self pay, and whose power wheelchair was paid for by Medicaid/DVR, Medicare, and self pay did not meet standard of care. Although these findings need to be correlated with long-term risks, such as overuse injuries, breakdowns, and participation, this study demonstrates that disparities in wheelchair procurement by insurance provider persist. PMID- 24211696 TI - One-year all-cause mortality after stroke: a prediction model. AB - OBJECTIVE: By using data from Department of Veterans Affairs (VA) national databases, this article presents and internally validates a 1-year all-cause mortality prediction index after hospitalization for acute stroke. DESIGN: An observational cohort. SETTING: VA medical centers. PARTICIPANTS: Veterans with a diagnosis of a new stroke who were discharged between October 1, 2006, and September 30, 2008. MAIN OUTCOME MEASURE: Death due to any cause that occurred between the index hospital discharge date and the 1-year anniversary of that date. RESULTS: Within 1-year after discharge, 1542 (12.3%) of the total 12,565 patients had died. Seventeen risk factors known at the point of hospital discharge remained in the predictive model of 1-year postdischarge mortality after backward selection, including advanced age, admission from extended care, type of stroke, 8 comorbid conditions, 4 types of procedures that occurred during the index hospitalization, hospital length of stay (longer than 3 weeks), and discharge location. We assigned a score to each variable in the final model and a risk score was determined for each patient by adding up the points for all risk factors present. According to these risk scores, the patients were divided into approximate quartiles that yielded low, moderate, high, and highest mortality likelihood strata. The risk of 1-year mortality ranged from 2.24% in the lowest quartile to 29.50% in the highest quartile in the derivation cohort and from 2.11%-30.77% in the validation cohort. Model discrimination demonstrated an area under the receiver operating characteristic curve of 0.785 in the derivation cohort and 0.787 in the validation cohort. The Hosmer-Lemeshow goodness of fit indicated that the model fit was adequate (P = .69). CONCLUSION: When using readily available data, a simple index that stratifies stroke patients at hospital discharge according to low, moderate, high, and highest likelihood of all-cause 1-year mortality is feasible and can inform the postdischarge planning process, depending on level of risk. PMID- 24211697 TI - The effect of neural lesion type on botulinum toxin dosage: a retrospective chart review. AB - BACKGROUND: It is difficult to compare the dosage of botulinum toxin between different neurologic conditions because of the different methods of reported dosages. Botulinum toxin is used to manage spasticity in variety of neurologic conditions, and it is important for clinicians to know whether there are differences in the dosage injected on the basis of the etiology of spasticity. OBJECTIVE: To determine whether the type of neural lesion influences the dosage of botulinum toxin required to manage spasticity. DESIGN: Retrospective chart review. SETTING: Review of patients who visited an outpatient spasticity clinic. PARTICIPANTS: We assessed medical charts from 99 patients with stroke, multiple sclerosis (MS), and cerebral palsy (CP) (n = 33 for each etiology). We collected information such as age, gender, weight, time of lesion, total dosage (per person, per limb, per muscle), injection location, and injections cycles. INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: OnabotulinumtoxinA dose - total dose in one leg was calculated as a sum of the units of the toxin injected in all the leg muscles. RESULTS: Total dose of toxin injected was 161 +/- 19 (mean +/- standard error of mean) in patients with stroke, 175 +/- 13 in patients with CP, and 225 +/- 18 in patients with MS. The total dose in the legs (normalized to body weight; units/kg) was significantly different between the 3 groups (stroke, CP, MS; P = .001). Subsequent post-hoc tests revealed that total dose in the legs of patients with MS was significantly greater (88%) than patients with stroke (P = .001). Hip adductors and hamstrings were injected most commonly in MS and CP, but toe muscles were commonly injected in patients with stroke, whereas plantar flexors were evenly injected all 3 patient groups. CONCLUSION: In our practice, we found that treating spasticity in people with MS required the greatest dose of botulinum toxin, followed by CP and then stroke. PMID- 24211698 TI - Back strength predicts walking improvement in obese, older adults with chronic low back pain. AB - OBJECTIVE: To compare the effects of 4 months of isolated lumbar resistance exercise and total body resistance exercise on walking performance in obese, older adults with chronic low back pain. A secondary analysis examined whether responsiveness to training modulated walking improvement. DESIGN: Randomized, controlled trial. SETTING: Research laboratory affiliated with tertiary care facility. METHODS AND INTERVENTION: Participants (N = 49; 60-85 years) were randomized into a 4-month resistance exercise intervention (TOTRX), lumbar extensor exercise intervention (LEXT), or a control group (CON). MAIN OUTCOME MEASUREMENTS: Walking performance, maximal low back strength and leg strength, and average resting and low back pain severity score (from an 11-point numerical pain rating scale; NRSpain) were collected at baseline and month 4. RESULTS: The TOTRX and LEXT improved lumbar extensor strength relative to CON, and the TOTRX (P < .05). NRSpain scores at month 4 were lowest in the TOTRX group compared with the LEXT and CON groups, respectively (2.0 +/- 1.7 points vs 3.7 +/- 2.6 points and 4.6 +/- 2.4 points; P < .006). A total of 53% and 67% of participants in the TOTRX and LEXT groups were responders who made lumbar extensor strength gains that achieved >=20% greater than baseline values. Although the TOTRX demonstrated the greatest improvement in walking endurance among the intervention groups, this did not reach significance (10.1 +/- 12.2% improvement in TOTRX vs 7.4 +/- 30.0% LEXT and -1.7 +/- 17.4% CON; P = .11). Gait speed increased most in the TOTRX (9.0 +/- 13.5%) compared with the LEXT and CON groups (P < .05). The change in lumbar extensor strength explained 10.6% of the variance of the regression model for the change in walking endurance (P = .024). CONCLUSIONS: The use of LEXT and TOTRX produced similar modest improvements in patients' walking endurance. Lumbar extensor strength gain compared with leg strength gain is a moderate but important contributor to walking endurance in obese older adults with chronic low back pain. Responders to resistance exercise programs (event those with only lumbar extension exercise) who make at least a 20% improvement in strength can expect better improvement in walking endurance than those who do not achieve this strength improvement. PMID- 24211699 TI - Amygdala-mediated enhancement of memory for specific events depends on the hippocampus. AB - Emotional events are often remembered better than neutral events, a type of memory prioritization by affective salience that depends on the amygdala. Studies with rats have indicated that direct activation of the basolateral complex of the amygdala (BLA) can enhance memory for neutral events, and if the activation is brief and temporally targeted, can do so in a way that benefits memories for specific events. The essential targets of BLA activation in the case of event specific memory enhancement were unknown, but the hippocampus was known to receive direct projections from the BLA and to support memory for events. In the present study, rats received counterbalanced infusions of either muscimol, a GABAA receptor agonist, or saline into the hippocampus prior to performing a novel object recognition memory task during which initial encounters with some of the objects were immediately followed by brief electrical stimulation to the BLA. When memory was tested 1day later in the saline condition, rats remembered these objects well but showed no memory for objects for which the initial encounter had not been followed by BLA stimulation. In contrast, no benefit to memory of BLA stimulation was observed in the muscimol condition. The results indicated that brief activation of the BLA can prioritize memories for events by enhancing memory for some object encounters but not others and that this benefit to memory depends on interactions between the amygdala and the hippocampus. PMID- 24211700 TI - Preference for high-fat diet is developed by young Swiss CD1 mice after short term feeding and is prevented by NMDA receptor antagonists. AB - Obesity is a worldwide epidemic that is increasing at an alarming rate. One of its causes is the increased availability and consumption of diets rich in fat. In the present study, we investigated the effects of short-term consumption of a high fat diet (HFD) on dietary preferences in Swiss CD1 mice and its relation in time to specific metabolic effects. Mice that were weaned 21days postpartum and fed a chow diet for one week were afterward subjected to a diet preference test for 5days, exposed to both a regular diet (RD) and HFD. We found that mice did not show any preferences. In a second experiment, two groups of mice that were weaned 21days postpartum and subjected to a chow diet for one week were fed either RD or HFD for 18days, and a diet preference test was performed for 5days. After this short-term consumption of HFD, mice preferred HFD, while mice subjected to RD did not show any preference. Importantly, no differences in blood glucose levels were found between the groups prior to and after the experiments. The results support our hypothesis that the preference for HFD is not a spontaneous behavior in CD1 mice, but it can be observed after short-term consumption; additionally, this preference develops before metabolic effects appear. Finally, this preference for HFD could not be observed when the mice were i.p. injected daily with low doses of the NMDA receptor antagonists, ketamine, ifenprodil or MK-801 during the HFD feeding period. These data suggest that acquisition of dietary preference for HFD is a NMDA receptor-dependent learning process. PMID- 24211701 TI - Tropomyosins induce neuritogenesis and determine neurite branching patterns in B35 neuroblastoma cells. AB - BACKGROUND: The actin cytoskeleton is critically involved in the regulation of neurite outgrowth. RESULTS: The actin cytoskeleton-associated protein tropomyosin induces neurite outgrowth in B35 neuroblastoma cells and regulates neurite branching in an isoform-dependent manner. CONCLUSIONS: Our data indicate that tropomyosins are key regulators of the actin cytoskeleton during neurite outgrowth. SIGNIFICANCE: Revealing the molecular machinery that regulates the actin cytoskeleton during neurite outgrowth may provide new therapeutic strategies to promote neurite regeneration after nerve injury. SUMMARY: The formation of a branched network of neurites between communicating neurons is required for all higher functions in the nervous system. The dynamics of the actin cytoskeleton is fundamental to morphological changes in cell shape and the establishment of these branched networks. The actin-associated proteins tropomyosins have previously been shown to impact on different aspects of neurite formation. Here we demonstrate that an increased expression of tropomyosins is sufficient to induce the formation of neurites in B35 neuroblastoma cells. Furthermore, our data highlight the functional diversity of different tropomyosin isoforms during neuritogenesis. Tropomyosins differentially impact on the expression levels of the actin filament bundling protein fascin and increase the formation of filopodia along the length of neurites. Our data suggest that tropomyosins are central regulators of actin filament populations which drive distinct aspects of neuronal morphogenesis. PMID- 24211702 TI - The beta2-adrenergic receptor as a surrogate odorant receptor in mouse olfactory sensory neurons. AB - In the mouse, mature olfactory sensory neurons (OSNs) express one allele of one of the ~1200 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express the same OR coalesce into homogeneous glomeruli at conserved positions in the olfactory bulb. ORs are involved in OR gene choice and OSN axonal wiring, but the mechanisms remain poorly understood. One approach is to substitute an OR genetically with another GPCR, and to determine in which aspects this GPCR can serve as a surrogate OR under experimental conditions. Here, we characterize a novel gene-targeted mouse strain in which the mouse beta2-adrenergic receptor (beta2AR) is coexpressed with tauGFP in OSNs that choose the OR locus M71 for expression (beta2AR->M71-GFP). By crossing these mice with beta2AR->M71-lacZ gene-targeted mice, we find that differentially tagged beta2AR->M71 alleles are expressed monoallelically. The OR coding sequence is thus not required for monoallelic expression - the expression of one of the two alleles of a given OR gene in an OSN. We detect strong beta2AR immunoreactivity in dendritic cilia of beta2AR->M71-GFP OSNs. These OSNs respond to the beta2AR agonist isoproterenol in a dose-dependent manner. Axons of beta2AR >M71-GFP OSNs coalesce into homogeneous glomeruli, and beta2AR immunoreactivity is detectable within these glomeruli. We do not find evidence for expression of endogenous beta2AR in OSNs of wild-type mice, also not in M71-expressing OSNs, and we do not observe overt differences in the olfactory system of beta2AR and beta1AR knockout mice. Our findings corroborate the experimental value of the beta2AR as a surrogate OR, including for the study of the mechanisms of monoallelic expression. PMID- 24211703 TI - A liposomal fluorescence assay to study permeation kinetics of drug-like weak bases across the lipid bilayer. AB - Lipid bilayer permeation is considered the major route for in vivo barrier passage of drugs. Despite this fact, no technique is currently available to measure the kinetics of permeation across a single lipid bilayer of structurally unrelated drug-like solutes. We developed a liposomal fluorescence assay capable to determine permeation kinetics of basic drug-like solutes across lipid bilayers. The assay is based on the hypothesis that permeation of a weak base along a concentration gradient results in net proton release at the cis-side and net proton capture at the trans-side of the bilayer. The resulting pH changes were monitored with pH-sensitive fluorophores: Test compounds were incubated with liposomes containing a pH-sensitive fluorophore at the bilayer surfaces or in the aqueous lumen and fluorescence changes were monitored with a stopped-flow apparatus in solution or by total internal reflection fluorescence microscopy with surface-captured liposomes on a microfluidic platform. Incubation with lipophilic basic drugs resulted in the expected fluorescence changes while incubation with compounds without basic functionality or high polarity did not affect fluorescence. Kinetics of fluorescence changes followed bi-exponential functions. Logarithmic permeation coefficients (logPermapp) determined in solution and by microfluidics technology showed a good correlation (r(2)=0.94, n=7) and logPermapp increased with increasing lipophilicity. Neither diffusion in the aqueous phase nor partitioning into the bilayer was rate-limiting. PEGylation of 2% of the liposomal lipids reduced Permapp by a factor ~300. In conclusion, the presented liposomal fluorescence assay is capable to determine permeation kinetics of weak basic drug-like solutes across lipid bilayers. The method is adaptable to microfluidics technology for high-throughput measurements and can potentially be modified to work for weak acid solutes. PMID- 24211704 TI - Nano-visualization of viral DNA breaching the nucleocytoplasmic barrier. AB - Nuclear pore complexes (NPCs) mediate all transport between the cytosol and the nucleus highly selectively. Their selectivity can become an insurmountable hurdle for exogenously applied therapeutic macromolecules. Many viruses naturally overcome the NPC barrier. Therefore, gene therapy often utilizes viral particles as nano-carriers for exogenous therapeutic macromolecules. Viral gene therapy, however, frequently leads to severe adverse effects. We intend to elucidate the mechanisms underlying controlled release of viral DNA at the NPC in order to design new non-viral approach for intranuclear DNA delivery. For this purpose, we developed a comprehensive experimental strategy combining nano-imaging and biochemical methods. Here, we apply Herpes simplex virus type 1 (HSV-1) as an ideal example. HSV-1 contains its long 145kbp DNA in a capsid which is merely 125nm in size. The capsid shields and targets the DNA specifically to the NPC. Only at the NPC, the capsid releases the DNA for nuclear delivery. The underlying mechanisms of this multi-step process remain unresolved. In this work we follow the fate of HSV-1 DNA in the process of transit across the NPC. Our results indicate an involvement of hydrophobicity for capsid opening. Furthermore, the DNA is presumably released as a single thread. We assume that it penetrates the NPC in this conformation. It is compacted by the host intranuclear proteins once it reaches the interior of the nucleus. Our proposed experimental strategy can be extended to other viruses. Moreover, our observations may help design potent non viral based nano-carriers for gene therapy. PMID- 24211705 TI - Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors. AB - Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface xi-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. PMID- 24211706 TI - Establishing high temperature gas chromatographic profiles of non-polar metabolites for quality assessment of African traditional herbal medicinal products. AB - The quality assessment of African traditional herbal medicinal products is a difficult challenge since they are complex mixtures of several herbal drug or herbal drug preparations. The plant source is also often unknown and/or highly variable. Plant metabolites chromatographic profiling is therefore an important tool for quality control of such herbal products. The objective of this work is to propose a protocol for sample preparation and gas chromatographic profiling of non-polar metabolites for quality control of African traditional herbal medicinal products. The methodology is based on the chemometric assessment of chromatographic profiles of non-polar metabolites issued from several batches of leaves of Combretum micranthum and Mitracarpus scaber by high temperature gas chromatography coupled to mass spectrometry, performed on extracts obtained in refluxed dichloromethane, after removal of chlorophyll pigments. The method using high temperature gas chromatography after dichloromethane extraction allows detection of most non-polar bioactive and non-bioactive metabolites already identified in leaves of both species. Chemometric data analysis using Principal Component Analysis and Partial Least Squares after Orthogonal Signal Correction applied to chromatographic profiles of leaves of Combretum micranthum and Mitracarpus scaber showed slight batch to batch differences, and allowed clear differentiation of the two herbal extracts. PMID- 24211707 TI - Application of a stabilizer cocktail of N-ethylmaleimide and phenylmethanesulfonyl fluoride to concurrently stabilize the disulfide and ester containing compounds in a plasma LC-MS/MS assay. AB - BMS-753493, a conjugate of the active epothilone moiety, BMS-748285, to folic acid, has been evaluated for the treatment of cancer. The presence of a disulfide bond in BMS-753493 and an ester group in both BMS-753493 and BMS-748285 results in their being unstable in blood or plasma. A stabilization strategy using a cocktail of N-ethylmaleimide and phenylmethanesulfonyl fluoride was developed and applied to stabilize both analytes in human blood during sample collection, processing, and storage. A rugged and accurate LC-MS/MS method was developed and validated for the quantitation of BMS-753493 and its active moiety, BMS-748285, in human plasma. The stabilized plasma samples were extracted by protein precipitation. Chromatographic separation was achieved on a Luna C8 analytical column with a gradient elution. Analytes and their stable isotope labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The standard curves, which ranged from 10.0 to 5000ng/mL for BMS 753493 and from 1.00 to 500ng/mL for BMS-748285, were fitted to a 1/x(2) weighted linear regression model. The intra-assay precision was within +/-2.0% CV and inter-assay precision was within +/-2.8% CV for both analytes. The assay accuracy was within +/-4.6% of the nominal values for both analytes. Assay recoveries were high (~80% for BMS-753493 and ~100% for BMS-748285) and internal standard normalized matrix effects were minimal. Both analytes were stable in stabilized human plasma for at least 24h at room temperature, 231 days at -20 degrees C, and following four freeze-thaw cycles. Incurred sample reanalysis played an important role in identifying a potential stability liability of the assay and helped improve the assay quality and robustness. The validated method was successfully applied to sample analysis in Phase I clinical studies. PMID- 24211708 TI - Simultaneous determination of probe drugs, metabolites, inhibitors and inducer in human plasma by liquid chromatography/tandem mass spectrometry and its application to pharmacokinetic study. AB - Cytochrome P450 3A4 (CYP3A4) and UDP-glucuronosyltransferase 1A1 (UGT1A1) are important enzymes responsible for the metabolism of many xenobiotics. To investigate their induction and inhibition properties, administering probe drugs and monitoring their concentration in plasma under the effects of inducers/inhibitors is the gold standard method. A rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of midazolam, raltegravir (probe drugs for CYP3A4 and UGT1A1), their major metabolites, 1'-hydroxymidazolam, 1'-hydroxymidazolam glucuronide and raltegravir glucuronide, rifampicin (inducer), ritonavir and ketoconazole (inhibitors). Analytes were extracted from 100MUl of plasma using solid-phase extraction followed by chromatographic separation on a reversed-phase C18 column (50mm*2.1mm, particle size 1.8MUm). The mass spectrometer was operated under positive ionization mode. Excellent linearity (r(2)>=0.995) was achieved for all. The method was validated and found to be accurate (88-111%), precise (CV%<13) and selective. Matrix effect was acceptable (88-118%) and analytes recovery was reproducible (60-95%). Analytes in plasma were also found to be stable in the autosampler (6 degrees C for 48h) and after two freeze-thaw cycles. We have developed a robust analytical method to simultaneously quantify probes, inducer and inhibitor of important drug metabolism enzymes. The method was successfully applied in a clinical study to investigate the degree of induction and inhibition of CYP3A4 and UGT1A1 among ethnic groups in Singapore. PMID- 24211709 TI - The specific PKR inhibitor C16 prevents apoptosis and IL-1beta production in an acute excitotoxic rat model with a neuroinflammatory component. AB - The double-stranded RNA-dependent protein kinase (PKR), an apoptotic inducer, regulates much pro-inflammatory cytokine production. The purpose of this study was to evaluate in vivo the effects of the specific PKR inhibitor C16 in the striatum in an acute excitotoxic rat model with an important neuroinflammatory component. Inflammation was induced by unilateral striatal injection of quinolinic acid (QA) in 10-week-old normotensive rats. Animals were separated into groups receiving either vehicle or C16 for both sham and QA rats. The effects were assessed in ipsi- and contralateral striata by immunoblotting for PKR activation, by Luminex assay for cytokine levels and by immunofluorescent staining for cleaved caspase-3 to detect neuronal apoptosis. The highest dose of C16 (600MUg/kg; C16-2) in QA rats reduced expression of the active catalytic domain of the PKR vs. that in vehicle-injected QA rats. A robust increase of IL 1beta levels on the contralateral side of QA rats was prevented by C16-2 (97% inhibition). Macroscopic and microscopic observation of cerebral tissue (Hematoxylin & Eosin staining) revealed that tissue integrity was more preserved with C16-2 treatment than its vehicle in QA rats. Furthermore, C16-2 treatment decreased by 47% the neuronal loss and by 37% the number of positive cleaved caspase-3 neurons induced by QA injection. In conclusion, C16 prevented not only the PKR-induced neuronal loss but also the inflammatory response in this acute excitotoxic in vivo model, highlighting its promising neuroprotective properties to rescue acute brain lesions. PMID- 24211710 TI - Impaired electro-genesis in skeletal muscle fibers of transgenic Alzheimer mice. AB - Alzheimer's disease (AD) is characterized by memory decline, but is often associated with non-cognitive symptoms, including muscular dysfunction. In the majority of cases these motor disturbances are seen when other neuro-degenerative disorders such as Parkinson's disease overlap dementia, however these can also be directly related to AD itself. Although the patho-mechanism remains largely unclear, beta-amyloid peptide (betaAP) is thought to be a key role-player in both the brain and periphery. Here we studied the electro-genesis of skeletal muscle fibers in a mouse transgenic AD model. Membrane potential was recorded by standard electro-physiological techniques. Compared to wild-type rodents, AD mice show severe disturbances in skeletal muscle electro-genesis manifested by significant depolarization of myo-fibers. These changes are not affected by short term betaAP treatment, the mark of a chronic degenerative process in the periphery directly related to AD whereby ion pumps on muscle membranes exhibit reduced activity. This phenomenon may explain ionic imbalance and cellular dysfunction both in the neuro-muscular system and in the brain. The observed motor disturbances might play a key role in impaired activities of daily living, and addressing the muscular patho-physiology could improve quality of life in AD. PMID- 24211711 TI - GLAST/EAAT1 regulation in cultured Bergmann glia cells: role of the NO/cGMP signaling pathway. AB - Glutamate, the major excitatory amino acid, activates a wide variety of signal transduction cascades. Ionotropic and metabotropic glutamate receptors are critically involved in long-term synaptic changes, although recent findings suggest that the electrogenic Na(+)-dependent glutamate transporters, responsible for its removal from the synaptic cleft participate in the signaling transactions triggered by this amino acid. Glutamate transporters are profusely expressed in glia therefore most of its uptake occurs in this cellular compartment. In the cerebellar cortex, Bergmann glial cells enwrap glutamatergic synapses and participate in the recycling of its neurotransmitter through the glutamate/glutamine shuttle. It has long been acknowledged that glutamatergic transmission in the cerebellar molecular layer results in cGMP accumulation within Bergmann glia cells. In this context, we decided to investigate a plausible role of the nitric oxide/cGMP-signaling pathway in the regulation of Bergmann glia glutamate transporters. To this end, the well-established model of primary cultures of chick cerebellar Bergmann glial cells was used. Confluent monolayers were exposed to the nitric oxide donor, sodium nitroprusside, or to the non-hydrolysable cGMP analog dbcGMP and the [(3)H] D-aspartate uptake activity measured. An increase in uptake activity, related to an augmentation in VMax, was detected with both treatments. The signaling cascade includes NO/cGMP/PKG and Ca(2+) influx through the Na(+)/Ca(2+) exchanger and might be related to the plasma membrane glutamate transporters turnover. Interestingly enough, an inhibitor of the cGMP dependent protein kinase was capable to abolish the sodium nitroprusside induced Ca(2+) influx. These results provide an insight into the physiological role of cGMP in the cerebellum. PMID- 24211712 TI - Preventing postpartum depression: a meta-analytic review. AB - This meta-analysis assessed the efficacy of a wide range of preventive interventions designed to reduce the severity of postpartum depressive symptoms or decrease the prevalence of postpartum depressive episodes. A systematic review identified 37 randomized or quasi-randomized controlled trials in which an intervention was compared to a control condition. Differences between treatment and control conditions in the level of depressive symptoms and prevalence of depressive episodes by 6 months postpartum were assessed in separate analyses. Depressive symptoms were significantly lower at post-treatment in intervention conditions, with an overall effect size in the small range after exclusion of outliers (Hedges' g=0.18). There was a 27% reduction in the prevalence of depressive episodes in intervention conditions by 6 months postpartum after removal of outliers and correction for publication bias. Later timing of the postpartum assessment was associated with smaller differences between intervention and control conditions in both analyses. Among studies that assessed depressive symptoms using the EPDS, higher levels of depressive symptoms at pre treatment were associated with smaller differences in depressive symptoms by 6 months postpartum. These findings suggest that interventions designed to prevent postpartum depression effectively reduce levels of postpartum depressive symptoms and decrease risk for postpartum depressive episodes. PMID- 24211714 TI - Regulatory and effector T-cells are differentially modulated by Dexamethasone. AB - It is assumed that the ratio between effector T cells (Teff) and regulatory T cells (Tregs) controls the immune reactivity within the T-cell compartment. The purpose of this study was to investigate if Dexamethasone (Dex) affects Teff and Tregs subsets. Dex induced on Tregs a dose and time-dependent apoptosis which resulted in a relative increase of Teff. After TCR activation, Dex induced a strong proliferative inhibition of Teff, but a weaker proliferative inhibition on Tregs. These effects were modulated by IL-2, which not only restored the proliferative response, but also prevented Dex-induced apoptosis. The highest dose of IL-2 prevented apoptosis on all FOXP3+CD4+ T cells. Meanwhile, the lowest dose only rescued activated Tregs (aTregs), probably related to their CD25 higher expression. Because Dex did not affect the suppressor capacity of aTregs either, our results support the notion that under Dex treatment, the regulatory T-cell compartment maintains its homeostasis. PMID- 24211713 TI - TSPAN33 is a novel marker of activated and malignant B cells. AB - We have identified Tspan33 as a gene encoding a transmembrane protein exhibiting a restricted expression pattern including expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in primary human B cells following activation. Human 2E2 cells, a Burkitt's lymphoma-derived B cell model of activation and differentiation, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in several lymphomas including Hodgkin's and Diffuse large B cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases where B cells participate in the pathology, including rheumatoid arthritis patients, systemic lupus erythematosus (SLE), and in spleen B cells from MRL/Fas(lpr/lpr) mice (a mouse model of SLE). We conclude that TSPAN33 may be used as a diagnostic biomarker or as a target for therapeutic antibodies for treatment of certain B cell lymphomas or autoimmune diseases. PMID- 24211715 TI - Th17 cell plays a role in the pathogenesis of Hashimoto's thyroiditis in patients. AB - Hashimoto's thyroiditis (HT) has long been epidemiologically associated with excess iodine levels. However, the underlying immunological mechanisms still remain largely unexplored. Th17 cells are commonly recognized as playing vital roles in various autoimmune diseases. Here we show that intra-thyroid infiltrating Th17 cells and serum IL-17 levels were significantly increased in HT patients. However, the concentration of serum IL-17 was inversely correlated with patients' residual thyroid function while the heterogeneously expressed thyroid IL-17 was directly correlated with local fibrosis. Administration of moderate high levels of iodine was found to facilitate the polarization of murine splenic naive T cells into Th17 cells, whereas extreme high levels of iodine favored Th1 polarization and inhibited Treg development. These findings suggest that both Th1 and Th17 cells may be involved in the pathogenesis of HT and high levels of iodine may play a critical role in this process by modulating T cell differentiation. PMID- 24211716 TI - A glycosylation-dependent CD45RB epitope defines previously unacknowledged CD27 IgM(high) B cell subpopulations enriched in young children and after hematopoietic stem cell transplantation. AB - The immune system is dysfunctional for years after hematopoietic stem cell transplantation (HSCT). A potential cause is an intrinsic B cell deficiency. In a cohort of pediatric HSCT patients few CD27(+) B cells formed after transplantation with the number of CD27(+)IgM(high) cells more affected than class-switched ones. A previously unacknowledged population of CD27(-)IgM(high) cells made up the majority of B cells and this population was also enlarged in healthy children compared to adults. Only a minority of these CD27(-)IgM(high) B cells expressed markers typical for transitional B cells, and the non transitional CD27(-)IgM(high) cells could be further divided into subpopulations based on their ability to extrude the dye Rhodamine 123 and their expression of CD45RB(MEM55), a glycosylation-dependent epitope. Thus, we define several novel human CD27(-)IgM(high) B cell subpopulations in blood, all of which are present in higher frequencies and numbers in young children and after HSCT than in adults. PMID- 24211718 TI - Effects of lentiviral-mediated Foxp1 and Foxq1 RNAi on the hepatocarcinoma cell. AB - Foxp1 and Foxq1 are two multifunctional molecules of "forkhead box (Fox)" family. The objective of this paper was to construct the lentiviral vectors expressing RNA interference (RNAi) against Foxp1 or Foxq1 genes, and the effects of both vectors with two RNAis on the proliferation, migration and apoptosis of 7721 hepatocarcinoma cell line were evaluated. Six target sequences against human Foxp1/Foxq1 mRNA were designed respectively and six pairs of their corresponding double-strand DNA oligo (siRNA) were synthesized prior to being transfected into 7721 cells with lipo2000, then a most efficient siRNA were selected to be subcloned into pLL3.7-GFP/Lenti plasmids. These plasmids were transfected into 293T cells to package lentiviral particles for subsequent transfection into 7721 cells after their sequences were confirmed. The expression of Foxp1and Foxq1 genes in the transfected cells were identified by real-time PCR. The migration, infiltration, viability and apoptosis of the transfected cells were assessed by wound healing assay, Transwell assay, CCK-8 assay and flow cytometry. Sequencing results showed that lentiviral vectors contained Foxp1 or Foxq1 gene. After being transfected into 7721 cells, Foxp1 and Foxq1 expression were significantly down regulated by siRNA-823 and siRNA-834. The migration and infiltration ability, and the viability of 7721 cells transfected with two siRNAs were significantly suppressed; flow cytometry assay exhibited the apoptosis rate of transfected 7721 cells with the lentivirus RNAi vector of Foxp1 or Foxq1 was increased. All the results showed that the lentivirus RNAi vectors of Foxp1 and Foxq1 were able to inhibit the expression of Foxp1 and Foxq1 in 7721 cells efficiently, and the down regulation of either Foxp1 or Foxq1 resulted in suppression of migration, infiltration and viability of 7721 cells and an increase in cell apoptosis. Our data indicated that both Foxp1 and Foxq1 genes played an oncogenic role in hepatocarcinoma cells, which proposed the two genes as new therapeutic targets for the cancer. PMID- 24211717 TI - A selective role of NKG2D in inflammatory and autoimmune diseases. AB - The NKG2D activating receptor has been implicated in numerous autoimmune diseases. We tested the role of NKG2D in models of autoimmunity and inflammation using NKG2D knockout mice and antibody blockade experiments. The severity of experimental autoimmune encephalitis (EAE) was decreased in NKG2D-deficient mice when the disease was induced with a limiting antigen dose, but unchanged with an optimal antigen dose. Surprisingly, however, NKG2D deficiency had no detectable effect in several other models, including two models of type 1 diabetes, and a model of intestinal inflammation induced by poly(I:C). NKG2D antibody blockade in normal mice also failed to inhibit disease in the NOD diabetes model or the intestinal inflammation model. Published evidence using NKG2D knockout mice demonstrated a role for NKG2D in mouse models of atherosclerosis and liver inflammation, as well as in chronic obstructive pulmonary disease. Therefore, our results suggest that NKG2D plays selective roles in inflammatory diseases. PMID- 24211719 TI - D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism. AB - Both excessive daytime sleepiness (EDS) and rapid eye movement (REM) sleep deregulation are part of Parkinson's disease (PD) non-motor symptoms and may complicate dopamine replacement therapy. We report here that dopamine agonists act differentially on sleep architecture in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine macaque monkey. Continuous sleep and wake electroencephalographic monitoring revealed no effect of the selective dopamine D2 receptor agonist quinpirole on EDS, whereas the selective dopamine D1 receptor agonist SKF38393 efficiently alleviated EDS and restored REM sleep to baseline values. The present results question the relevance of abandoning D1 receptor agonist treatment in PD as it might actually improve sleep-related disorders. PMID- 24211720 TI - RIG-I-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I. AB - RIG-I-like receptors (RLRs) are nucleic acid sensors that activate antiviral innate immune response. These molecules recognize diverse non-self RNA substrates and are antagonized by several viral inhibitors. We performed an evolutionary analysis of RLR genes (RIG-I, MDA5, and LGP2) in mammals. Results indicated that purifying selection had a dominant role in driving the evolution of RLRs. However, application of maximum-likelihood analyses identified several positions that evolved adaptively. Positively selected sites are located in all domains of MDA5 and RIG-I, whereas in LGP2 they are confined to the helicase domain. In both MDA5 and RIG-I, the linkers separating the caspase activation and recruitment domain and the helicase domain represented preferential targets of positive selection. Independent selective events in RIG-I and LGP2 targeted the corresponding site (Asp421 and Asp179, respectively) within a protruding alpha helix that grips the V-shaped structure formed by the pincer. Most of the positively selected sites in MDA5 are in regions unique to this RLR, including a characteristic insertion within the helicase domain. Additional selected sites are located at the contact interface between MDA5 monomers, in spatial proximity to a positively selected human polymorphism (Arg843His) and immediately external to the parainfluenza virus 5 V protein binding region. Structural analyses suggested that the positively selected His834 residue is involved in parainfluenza virus 5 V protein binding. Data herein suggest that RLRs have been engaged in host-virus genetic conflict leading to diversifying selection and indicate parallel evolution at the same site in RIG-I and LGP2, a position likely to be of central importance in antiviral responses. PMID- 24211721 TI - Exploring the minimally frustrated energy landscape of unfolded ACBP. AB - The unfolded state of globular proteins is not well described by a simple statistical coil due to residual structural features, such as secondary structure or transiently formed long-range contacts. The principle of minimal frustration predicts that the unfolded ensemble is biased toward productive regions in the conformational space determined by the native structure. Transient long-range contacts, both native-like and non-native-like, have previously been shown to be present in the unfolded state of the four-helix-bundle protein acyl co-enzyme binding protein (ACBP) as seen from both perturbations in nuclear magnetic resonance (NMR) chemical shifts and structural ensembles generated from NMR paramagnetic relaxation data. To study the nature of the contacts in detail, we used paramagnetic NMR relaxation enhancements, in combination with single-point mutations, to obtain distance constraints for the acid-unfolded ensemble of ACBP. We show that, even in the acid-unfolded state, long-range contacts are specific in nature and single-point mutations affect the free-energy landscape of the unfolded protein. Using this approach, we were able to map out concerted, interconnected, and productive long-range contacts. The correlation between the native-state stability and compactness of the denatured state provides further evidence for native-like contact formation in the denatured state. Overall, these results imply that, even in the earliest stages of folding, ACBP dynamics are governed by native-like contacts on a minimally frustrated energy landscape. PMID- 24211722 TI - Tapentadol enantiomers: Synthesis, physico-chemical characterization and cyclodextrin interactions. AB - The complete physico-chemical characterization of the single enantiomer analgesic drug R,R-tapentadol was quantitated in terms of protonation macro- and microconstants and octanol-water partition coefficient using pH-potentiometry, UV pH and (1)H NMR-pH titrations. The protonation macroconstants were found to be logK1=10.59+/-0.01 and logK2=9.44+/-0.01, while the individual basicity of each protonation site was found to be logk(O)=9.94 and logk(N)=10.48 for the phenolate and tertiary amine functions, respectively. As a consequence, the zwitterionic form of tapentadol predominates in aqueous solutions. The potential optical impurity (S,S-tapentadol) was synthesized for the first time in a seven-step chiral synthetic procedure. The enantiomers of tapentadol were separated by cyclodextrin modified capillary zone electrophoresis. Over 15 cyclodextrins were investigated in terms of apparent complex stability and screened as chiral selectors, and the sulfated alpha-cyclodextrin was found to resolve the enantiomers with excellent resolution (Rs=16.2 and 9.1) at pH 4.75 and pH 9.0, respectively. The system containing 12mM selector in a 50mM TRIS-acetate buffer was amenable to detect S,S-tapentadol potential optical impurity at 0.1% concentration level. PMID- 24211723 TI - New method of screening allergenic components from Shuanghuanglian injection: with RBL-2H3/CMC model online HPLC/MS system. AB - Shuanghuanglian (SHL) injection is a traditional Chinese medicine (TCM) injection widely used in China to treat influenza, tonsillitis, bronchitis, and faucitis. Adverse drug reactions (ADR) of SHL injection, majorly manifested as allergic reactions, were among the leading causes of death from TCM injection. In this study, an RBL-2H3/CMC online LC/MS system was established to screen and identify allergenic components in SHL injection, by which Baicalin was identified as a potential allergenic component. Allergenic activities of baicalin were investigated in RBL-2H3 cell degranulation and beta-hexosaminidase release tests in vitro. Our results showed that baicalin dose-dependently induced RBL-2H3 cell degranulation and beta-hexosaminidase release in the range of 0-50MUg/ml. The RBL 2H3/CMC online LC/MS system developed in this study may potentially be used to screen allergenic components in other TCM injections. PMID- 24211724 TI - LC-MS/MS characterization of forced degradation products of zofenopril. AB - A rapid, specific and reliable isocratic LC-MS/MS method has been developed and validated for the identification and characterization of stressed degradation products of Zofenopril. Zofenopril, an anti-hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH-specified conditions. The drug showed extensive degradation under oxidative and base hydrolysis stress conditions. However, it was stable to thermal, acid, neutral and photolysis stress conditions. A total of 6 degradation products were observed and the chromatographic separation of the drug and its degradation products were achieved on Phenomenex (Luna) C18 (250mm*4.6mm, i.d., 5MUm) column using 20mM ammonium acetate: acetonitrile (50:50, v/v) as a mobile phase. The degradation products were characterized by LC-MS/MS and its fragmentation pathways were proposed. The LC-MS method was validated with respect to specificity, linearity, accuracy and precision. No previous reports were found in the literature regarding the degradation behavior of zofenopril. PMID- 24211725 TI - Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts. AB - Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. PMID- 24211726 TI - Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain. AB - Although nerve injury-induced long-term postsynaptic changes have been investigated, less is known regarding the molecular mechanisms within presynaptic axonal terminals. We investigated the molecular changes in presynaptic nerve terminals underlying chronic pain-induced plastic changes in the medial prefrontal cortex (mPFC). After neuropathic pain was induced by spared nerve injury (SNI) in rats, we assessed the release of the excitatory neurotransmitter glutamate by using in vitro synaptosomal preparations from the mPFC. We also measured the levels of synaptic proteins and protein kinases in synaptosomes using Western blotting. The results showed that unilateral long-term SNI augmented depolarization-evoked glutamate release from synaptosomes of the bilateral mPFC. This result was confirmed by a rapid destaining rate of FM1-43 dye in SNI-operated rats. Unilateral long-term nerve injury also significantly increased synaptic proteins (including synaptophysin, synaptotagmin, synaptobrevin, syntaxin, and 25-kDa synaptosome-associated protein) in synaptosomal fractions from the bilateral mPFC, and ultrastructure images demonstrated increased synaptic vesicular profiles in synaptosomes from SNI animals. Chronic pain upregulated the phosphorylation of endogenous protein kinases, including extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Ca(2+)/calmodulin-dependent kinase II (CaMKII), and synapsin I, the primary presynaptic target of ERK1/2 and CaMKII. Both presynaptic proteins and protein kinases were upregulated after SNI in a time-dependent manner. These results indicate that the long-term neuropathic pain-induced enhancement of glutamate release in the mPFC is linked to increased synaptic vesicle proteins and the activation of the ERK1/2- and CaMKII-synapsin signaling cascade in presynaptic axonal terminals. PMID- 24211727 TI - Serum vascular adhesion protein-1 predicts all-cause mortality and cancer-related mortality in subjects with colorectal cancer. AB - BACKGROUND: Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 can predict cancer mortality, including colorectal cancer (CRC) mortality, in type 2 diabetic subjects. However, it remains unknown if serum VAP-1 can predict mortality in CRC patients. This prospective cohort study investigates if serum VAP-1 is a novel biomarker for mortality prediction in CRC. METHODS: We enrolled 300 CRC patients. Preoperative serum VAP-1 was measured by time-resolved immunofluorometric assay. They were followed until September 2009 or death, which was ascertained by the National Death Registration System. RESULTS: The median follow-up period was 4.7 years. Compared with normal counterpart, VAP-1 immunoactivity was upregulated in CRC tissues, especially at the invasion front. Serum VAP-1 can independently predict all-cause mortality (HR: 1.0026, 95% CI: 1.0003-1.0050, P<0.05) and cancer-related mortality (HR: 1.0026, 95% CI: 1.0001-1.0050, P<0.05). A risk score composed of age, gender, carcinoembryonic antigen (CEA) >5 ng/ml, tumor grading, tumor staging, and serum VAP-1 could stratify CRC patients into low-, intermediate-, and high-risk subgroups, with a 5-year mortality rate of 10%, 34%, and 78%, respectively. CONCLUSIONS: Serum VAP-1 predicts mortality independently and improves risk stratification in CRC subjects. PMID- 24211728 TI - Analytical and preanalytical validation of a new mass spectrometric serum 5 hydroxyindoleacetic acid assay as neuroendocrine tumor marker. AB - BACKGROUND: Serum 5-hydroxyindoleacetic acid (5-HIAA) could replace the determination of 24-h urinary 5-HIAA for diagnosis and follow-up of neuroendocrine tumors (NETs). We developed and validated a straightforward liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for serum 5-HIAA. METHODS: We used serum samples from healthy volunteers (n=136) and patients suspected or followed for NET (n=129). Samples were spiked with 5-HIAA-D2, extracted and quantified by LC-MS/MS. We studied the effects of sample storage, sample device, a meal and diurnal variation on serum 5-HIAA. Furthermore, we established a reference range for serum 5-HIAA and compared our assay with a urinary 5-HIAA HPLC assay and a commercial plasma chromogranin A (CgA) immunoassay. RESULTS: Our LC-MS/MS assay is sensitive (LOQ 5 nmol/L), has a wide assay range (5-10,000 nmol/L) and short analysis time (7 min). 5-HIAA in serum is stable for several days in various temperatures and during five freeze-thaw cycles. We found no diurnal variation (p >= 0.20) and a meal had no effect on serum 5-HIAA (p=0.89). We suggest an upper reference limit of 123 nmol/L for serum 5-HIAA. The area under curve (AUC) in receiver operator characteristics (ROC) analysis was 0.83 for urinary 5-HIAA, 0.81 for serum 5-HIAA and 0.76 for CgA, respectively. CONCLUSIONS: The LC-MS/MS assay for serum 5-HIAA discriminates between healthy individuals and patients with NET and is well suited for the diagnosis and follow-up of NETs. PMID- 24211729 TI - Recommendation to harmonize the units for reporting cardiac troponin results. PMID- 24211730 TI - Using remote sensing to define environmental characteristics related to physical activity and dietary behaviours: a systematic review (the SPOTLIGHT project). AB - We performed a systematic literature review on the use of free geospatial services as potential tools to assess built environmental characteristics related to dietary behaviour and physical activity. We included 13 studies, all published since 2010 and conducted in urban contexts, with Google Earth and Google Street View as the two main free geospatial services used. The agreement between virtual and field audit was higher for items related to objectively verifiable measures (e.g. presence of infrastructure and equipment) and lower for subjectively assessed items (e.g. aesthetics, street atmosphere, etc.). Free geospatial services appear as promising alternatives to field audit for assessment of objective dimensions of the built environment. PMID- 24211731 TI - Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-D structures on inflammation. AB - Recent studies have pointed towards a decisive role of inflammation in triggering tissue repair and regeneration, while at the same time it is accepted that an exacerbated inflammatory response may lead to rejection of an implant. Within this context, understanding and having the capacity to regulate the inflammatory response elicited by 3-D scaffolds aimed for tissue regeneration is crucial. This work reports on the analysis of the cytokine profile of human monocytes/macrophages in contact with biodegradable 3-D scaffolds with different surface properties, architecture and controlled pore geometry, fabricated by 3-D printing technology. Fabrication processes were optimized to create four different 3-D platforms based on polylactic acid (PLA), PLA/calcium phosphate glass or chitosan. Cytokine secretion and cell morphology of human peripheral blood monocytes allowed to differentiate on the different matrices were analyzed. While all scaffolds supported monocyte/macrophage adhesion and stimulated cytokine production, striking differences between PLA-based and chitosan scaffolds were found, with chitosan eliciting increased secretion of tumor necrosis factor (TNF)-alpha, while PLA-based scaffolds induced higher production of interleukin (IL)-6, IL-12/23 and IL-10. Even though the material itself induced the biggest differences, the scaffold geometry also impacted on TNF-alpha and IL-12/23 production, with chitosan scaffolds having larger pores and wider angles leading to a higher secretion of these pro-inflammatory cytokines. These findings strengthen the appropriateness of these 3-D platforms to study modulation of macrophage responses by specific parameters (chemistry, topography, scaffold architecture). PMID- 24211732 TI - Biodegradation of metallic magnesium elicits an inflammatory response in primary nasal epithelial cells. AB - Resorbable magnesium-based implants hold great promise for various biomedical applications, such as osteosynthesis and coronary stenting. They also offer a new therapeutic option for the treatment of chronic rhinosinusitis, but little data is yet available regarding the use of magnesium in the nasal cavity. To model this field of application, primary porcine nasal epithelial cells were used to test the biocompatibility of degrading pure magnesium and investigate whether the degradation products may also affect cellular metabolism. Magnesium specimens did not induce apoptosis and we found no major influence on enzyme activities or protein synthesis, but cell viability was reduced and elevated interleukin 8 secretion indicated proinflammatory reactions. Necrotic damage was most likely due to osmotic stress, and our results suggest that magnesium ion build-up is also involved in the interleukin 8 release. Furthermore, the latter seems to be mediated, at least in part, by the p38 signaling pathway. These effects probably depended on the accumulation of very high concentrations of magnesium ions in the in vitro set-up, which might not be achieved in vivo, although we cannot exclude that further, as yet unknown, factors played a role in the inflammatory response during the degradation process. In conclusion, the biocompatibility of pure magnesium with cells in the immediate vicinity appears less ideal than is often supposed, and this needs to be considered in the evaluation of magnesium materials containing additional alloying elements. PMID- 24211733 TI - Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment. AB - Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering. PMID- 24211734 TI - Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis--a review. AB - A systematic analysis of results available from in vitro, in vivo and clinical trials on the effects of biocompatible calcium phosphate (CaP) coatings is presented. An overview of the most frequently used methods to prepare CaP-based coatings was conducted. Dense, homogeneous, highly adherent and biocompatible CaP or hybrid organic/inorganic CaP coatings with tailored properties can be deposited. It has been demonstrated that CaP coatings have a significant effect on the bone regeneration process. In vitro experiments using different cells (e.g. SaOS-2, human mesenchymal stem cells and osteoblast-like cells) have revealed that CaP coatings enhance cellular adhesion, proliferation and differentiation to promote bone regeneration. However, in vivo, the exact mechanism of osteogenesis in response to CaP coatings is unclear; indeed, there are conflicting reports of the effectiveness of CaP coatings, with results ranging from highly effective to no significant or even negative effects. This review therefore highlights progress in CaP coatings for orthopaedic implants and discusses the future research and use of these devices. Currently, an exciting area of research is in bioactive hybrid composite CaP-based coatings containing both inorganic (CaP coating) and organic (collagen, bone morphogenetic proteins, arginylglycylaspartic acid etc.) components with the aim of promoting tissue ingrowth and vascularization. Further investigations are necessary to reveal the relative influences of implant design, surgical procedure, and coating characteristics (thickness, structure, topography, porosity, wettability etc.) on the long-term clinical effects of hybrid CaP coatings. In addition to commercially available plasma spraying, other effective routes for the fabrication of hybrid CaP coatings for clinical use still need to be determined and current progress is discussed. PMID- 24211735 TI - Establishing a versatile Golden Gate cloning system for genetic engineering in fungi. AB - The corn pathogen Ustilago maydis is a well-studied fungal model organism. Along with a broad set of experimental tools, versatile strategies for the generation of gene replacement mutants by homologous recombination in U. maydis have been developed. Nevertheless, the production of corresponding linear DNA constructs still constitutes a time-limiting step. To overcome this bottleneck, various resistance cassette modules were adopted for use with the so-called Golden Gate cloning strategy. These modules allow not only simple gene deletions but also more sophisticated genetic manipulations like inserting sequences for C-terminal protein tagging. The type IIs restriction enzyme BsaI was selected for this novel approach as its recognition sites are comparatively rare in the U. maydis genome. To test the efficiency of the new strategy it was used to test the influence of varying flank lengths as well as the effect of non-homologous flank ends on homologous recombination. Importantly, to proof a broad applicability in other fungi the same strategy was used to generate mutants in the filamentous ascomycete Aspergillus nidulans. Hence, we present a highly efficient and economic cloning strategy that speeds up reverse genetic approaches in fungi. PMID- 24211736 TI - Hyb: a bioinformatics pipeline for the analysis of CLASH (crosslinking, ligation and sequencing of hybrids) data. AB - Associations between proteins and RNA-RNA duplexes are important in post transcriptional regulation of gene expression. The CLASH (Cross-linking, Ligation and Sequencing of Hybrids) technique captures RNA-RNA interactions by physically joining two RNA molecules associated with a protein complex into a single chimeric RNA molecule. These events are relatively rare and considerable effort is needed to detect a small number of chimeric sequences amongst millions of non chimeric cDNA reads resulting from a CLASH experiment. We present the "hyb" bioinformatics pipeline, which we developed to analyse high-throughput cDNA sequencing data from CLASH experiments. Although primarily designed for use with AGO CLASH data, hyb can also be used for the detection and annotation of chimeric reads in other high-throughput sequencing datasets. We examined the sensitivity and specificity of chimera detection in a test dataset using the BLAST, BLAST+, BLAT, pBLAT and Bowtie2 read alignment programs. We obtained the most reliable results in the shortest time using a combination of preprocessing with Flexbar and subsequent read-mapping using Bowtie2. The "hyb" software is distributed under the GNU GPL (General Public License) and can be downloaded from https://github.com/gkudla/hyb. PMID- 24211738 TI - Anatomy of the liver: an outline with three levels of complexity--a further step towards tailored territorial liver resections. AB - The vascular anatomy of the liver can be described at three different levels of complexity according to the use that the description has to serve. The first- conventional--level corresponds to the traditional 8-segments scheme of Couinaud and serves as a common language between clinicians from different specialties to describe the location of focal hepatic lesions. The second--surgical--level, to be applied to anatomical liver resections and transplantations, takes into account the real branching of the major portal pedicles and of the hepatic veins. Radiological and surgical techniques exist nowadays to make full use of this anatomy, but this requires accepting that the Couinaud scheme is a simplification, and looking at the vascular architecture with an unprejudiced eye. The third--academic--level of complexity concerns the anatomist, and the need to offer a systematization that resolves the apparent contradictions between anatomical literature, radiological imaging, and surgical practice. Based on the real number of second-order portal branches that, although variable averages 20, we submit a system called the "1-2-20 concept", and suggest that it fits best the number of actual--as opposed to idealized--anatomical liver segments. PMID- 24211739 TI - MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity. AB - BACKGROUND & AIMS: Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). METHODS: MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. RESULTS: MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. CONCLUSION: Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC. PMID- 24211740 TI - Timing and benefit of liver transplantation in acute liver failure. AB - The case for using emergency liver transplantation in acute liver failure was made two decades ago by a series of single centre experiences. The development of models identifying a poor prognosis assisted the selection of patients for liver transplantation but none of these delivers both high sensitivity and specificity for prediction of death. Enhanced sensitivity favours the individual patient while enhanced specificity targets the pool of organs available at those who will derive greatest benefit. The non-transplant survival rates have improved considerably for certain cohorts of patients and these prognostic models have not been adjusted to reflect these changes. The presumption of transplant benefit can no longer be taken as established in paracetamol-related acute liver failure and a policy review is appropriate. In other scenarios, such as seronegative hepatitis and the phenotype of sub-acute liver failure, spontaneous survival rates remain low and the basis for liver transplantation remains sound. Outcomes after liver transplantation are improving but are not yet comparable to elective transplantation. The understanding of factors associated with failure after liver transplantation is improving but accurate definition of futility has not yet been attained. PMID- 24211737 TI - Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants. AB - BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naive, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14 weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48 weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log10 IU/ml compared to ? 8 log10 IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses. PMID- 24211741 TI - The clinical course of cirrhosis. Population based studies and the need of personalized medicine. PMID- 24211742 TI - Coordinated care in cirrhosis; the need for further randomized controlled trials. PMID- 24211743 TI - Long term results of liver transplantation for Wilson's disease: experience in France. AB - BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18 66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7 53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5 42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33 180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (<1%), which achieves an excellent long-term outcome, including renal function. PMID- 24211744 TI - Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study. AB - BACKGROUND & AIMS: Detecting portal hypertension (PH) before the development of varices is important for prognosis and for designing interventional studies. None of the available strategies is used in practice. We evaluated a sequential screening-diagnostic strategy based on clinical data and transient elastography (TE) to detect PH in asymptomatic outpatients with liver disease. METHODS: Consecutive patients with chronic liver disease and no previous diagnosis of PH were screened by TE. Patients with liver stiffness (LS) ? 13.6 kPa were further evaluated by endoscopy and hepatic venous pressure gradient (HVPG). For analysis, patients were classified in 3 groups: group A, platelets ? 150,000/mm(3), normal abdominal ultrasound; group B, platelets <150,000/mm(3), normal ultrasound; group C, platelets <150,000/mm(3), abnormal ultrasound (splenomegaly, nodular liver surface). RESULTS: 250 patients were evaluated (69% group A, 20% group B, 11% group C). In 9% elastography was non-valid. LS ? 13.6 was found in 54 patients (8% A, 43% B, and 81% C, p<0.001). Endoscopy was performed in 49 of these: 20% had small varices, 0% high-risk varices. No patients from group A had varices, and 90% with varices belonged to group C. HVPG was obtained in 40 patients: 93% had PH (HVPG >5 mmHg) and 65% clinically significant PH (CSPH, HVPG ? 10). Only 3 patients, all from group A, had HVPG <5. All patients from groups B and C with LS ? 13.6 had PH. The LS 25 cut-off was excellent at ruling-in CSPH. CONCLUSIONS: A simple strategy based on routine clinical data and TE could be useful to detect early PH among asymptomatic patients with chronic liver disease. PMID- 24211745 TI - Astilbin protects diabetic rat heart against ischemia-reperfusion injury via blockade of HMGB1-dependent NF-kappaB signaling pathway. AB - Astilbin, a flavonoid compound was isolated from the rhizome of Smilax china L. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effect of Astilbin on diabetic rats in vivo and elucidated the potential mechanism in vitro. The results showed that Astilbin significantly attenuated hypoxia-induced cell injury in a concentration-dependent manner. Treatment of H9c2 cells with Astilbin at 15 MUM blocked nuclear factor kappaB (NF-kappaB) phosphorylation by blocking High-mobility group box protein 1 (HMGB1) expression. Treatment of diabetic rats with Astilbin by intravenous injection (i.v.) at a single dose of 50 mg/kg protected the rats from myocardial I/R injury as indicated by decreasing infarct volume, improving hemodynamics and reducing myocardial damage, and also lowered serum levels of pro-inflammatory factors, reduced HMGB1 and phosphorylated NF-kappaB expression in ischemic myocardial tissue from diabetic rats. Additionally, treatment of diabetic rats with Astilbin at dose of 50 mg/kg by i.v. for continuous 14 days attenuated cardiac remodeling in the model myocardial I/R injury. These protective effects suggested that Astilbin might be due to block of the myocardial inflammatory cascade via the HMGB1-dependent NF-kappaB signaling pathway. PMID- 24211746 TI - The inflammatory mediator leukotriene D4 induces subcellular beta-catenin translocation and migration of colon cancer cells. AB - The abnormal activation of the Wnt/beta-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of beta-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D4 (LTD4) exerts its effects through the CysLT1 receptor. We previously reported an upregulation of CysLT1R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD4 on Wnt/beta catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD4 stimulation led to an increase in beta-catenin expression, beta catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD4 significantly reduced the expression of E-cadherin and beta catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD4 can be blocked by the inhibition of CysLT1R. Furthermore, LTD4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3beta activity, indicating a crosstalk between the G-protein-coupled receptor CysLT1 and the Wnt/beta-catenin pathway. In conclusion, LTD4, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces beta-catenin translocation and the activation of beta-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. PMID- 24211747 TI - MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated. AB - Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3'UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM. PMID- 24211748 TI - Protein engineering and the use of molecular modeling and simulation: the case of heterodimeric Fc engineering. AB - Computational and structure guided methods can make significant contributions to the development of solutions for difficult protein engineering problems, including the optimization of next generation of engineered antibodies. In this paper, we describe a contemporary industrial antibody engineering program, based on hypothesis-driven in silico protein optimization method. The foundational concepts and methods of computational protein engineering are discussed, and an example of a computational modeling and structure-guided protein engineering workflow is provided for the design of best-in-class heterodimeric Fc with high purity and favorable biophysical properties. We present the engineering rationale as well as structural and functional characterization data on these engineered designs. PMID- 24211749 TI - The effects of cell compressibility, motility and contact inhibition on the growth of tumor cell clusters using the Cellular Potts Model. AB - There are numerous biological examples where genes associated with migratory ability of cells also confer the cells with an increased fitness even though these genes may not have any known effect on the cell mitosis rates. Here, we provide insight into these observations by analyzing the effects of cell migration, compression, and contact inhibition on the growth of tumor cell clusters using the Cellular Potts Model (CPM) in a monolayer geometry. This is a follow-up of a previous study (Thalhauser et al. 2010) in which a Moran-type model was used to study the interaction of cell proliferation, migratory potential and death on the emergence of invasive phenotypes. Here, we extend the study to include the effects of cell size and shape. In particular, we investigate the interplay between cell motility and compressibility within the CPM and find that the CPM predicts that increased cell motility leads to smaller cells. This is an artifact in the CPM. An analysis of the CPM reveals an explicit inverse-relationship between the cell stiffness and motility parameters. We use this relationship to compensate for motility-induced changes in cell size in the CPM so that in the corrected CPM, cell size is independent of the cell motility. We find that subject to comparable levels of compression, clusters of motile cells grow faster than clusters of less motile cells, in qualitative agreement with biological observations and our previous study. Increasing compression tends to reduce growth rates. Contact inhibition penalizes clumped cells by halting their growth and gives motile cells an even greater advantage. Finally, our model predicts cell size distributions that are consistent with those observed in clusters of neuroblastoma cells cultured in low and high density conditions. PMID- 24211750 TI - Comparison of cost-utility between automated peritoneal dialysis and continuous ambulatory peritoneal dialysis. AB - BACKGROUND AND AIMS: The use of automated peritoneal dialysis (APD) is increasing compared to continuous ambulatory peritoneal dialysis (CAPD). Surprisingly, little data about health benefits and cost of APD exist, and virtually no information comparing the cost-utility between CAPD and APD is available. We undertook this study to evaluate and compare the health-related quality of life (HRQOL) and cost-utility indexes in patients on CAPD vs. APD METHODS: This was a prospective cohort of patients initiating dialysis (2008-2009). Two questionnaires were self-administered: European Research Questionnaire Quality of Life (EQ-5D) and Kidney Disease Quality of Life (short form, KDQOL-SF, Rand, Santa Monica, CA). Direct medical costs (DMC) were determined from the health provider perspective including the following medical resource utilization: outpatient clinic/emergency care, dialysis procedures, medications, laboratory tests, hospitalization, and surgery. Cost-utility indexes were calculated dividing total mean cost by indicators of the HRQOL. RESULTS: One hundred twenty three patients were evaluated: 77 on CAPD and 46 on APD. Results of the EQ-5D and KDQOL-SF questionnaires were significantly better in APD compared to the CAPD group. Main costs in both APD and CAPD were attributed to hospitalization and dialysis procedures followed by medication and surgery. Outpatient clinic visits and laboratory tests were significantly more costly in CAPD than in APD, whereas dialysis procedures were more expensive in the latter. Cost-utility indexes were significantly better in APD compared to CAPD. CONCLUSIONS: A significant cost utility advantage of APD vs. CAPD was observed. The annual DMC per-patient were not different between groups but the HRQOL was better in the APD compared to the CAPD group. PMID- 24211751 TI - Anti-inflammatory interventions in end-stage kidney disease: a randomized, double blinded, controlled and crossover clinical trial on the use of pravastatin in continuous ambulatory peritoneal dialysis. AB - BACKGROUND AND AIMS: Inflammation is highly prevalent in patients on dialysis. Statins have anti-inflammatory actions but their use has been scarcely studied in continuous ambulatory peritoneal dialysis (CAPD). We undertook this study to compare the effect of pravastatin vs. placebo on the serum concentrations of C reactive protein (CRP) in patients on CAPD. METHODS: In a double-blind, controlled and crossover clinical trial, 76 CAPD patients were randomized to either pravastatin or placebo for 2 months. After this first period of treatment, patients had a 1-month wash-out period and, finally, they were crossed-over to receive the other drug (or placebo) for 2 more months. Measurement of clinical and biochemical variables and CRP was performed at the beginning and at the end of each treatment period. RESULTS: Median CRP was only significantly decreased in the pravastatin group in both periods of treatment: first period (baseline vs. final, mg/L): pravastatin 7.4 (2-21) vs. 2.6 (1-6), p <0.05; placebo 3.9 (2-10) vs. 6.8 (3-12), pNS; second period: pravastatin 4.3 (2-15) vs. 1.9 (1-7), p <0.05; placebo 4.9 (2-17) vs. 6.8 (2-19), p <0.05. Results were significantly different (p <0.05) between groups only at the end of each treatment period. Additionally, total and LDL-cholesterol significantly decreased in the pravastatin group. CONCLUSIONS: Pravastatin significantly reduced serum levels of CRP and total and LDL-cholesterol compared to placebo. This treatment may be of great help to decrease the inflammatory status and probably the cardiovascular disease of CAPD patients. PMID- 24211752 TI - Vascular calcification in Mexican hemodialysis patients. AB - BACKGROUND AND AIMS: Vascular calcification (VC) is a predictor of poor survival and cardiovascular outcome in end-stage renal disease (ESRD) patients; however, there is scarce information of VC in Latin America, and virtually no data in our setting. We undertook this study to evaluate the prevalence and characteristics of VC in a hemodialysis (HD) population from western Mexico and to determine possible associated factors. METHODS: This was a cross-sectional study performed in 52 patients. VC was evaluated using plain X-ray films (Adragao's score) of hands and pelvis; clinical and biochemical variables were also collected. Statistical analysis was carried out with Student t and chi(2) tests performed as appropriate and logistic regression to determine predictors of VC. RESULTS: Mean age was 43 years, 48% were female, 23% had diabetes mellitus (DM), and median time on dialysis was 46 months. Percentage prevalence was 52% with a mean calcification score of 2.0 +/- 2.6; 23% of patients had severe calcification. VC was present in about 23-37% among the different vascular territories evaluated (radial, digital, femoral and iliac). Patients with calcification were significantly older, had a higher frequency of DM, higher alkaline phosphatase and lower HDL lipoproteins than those without VC. In the multivariate analysis, VC in these patients was significantly predicted only by an older age (OR [95% CI]: 1.15 [1.01-1.31], p = 0.04); lower HDL-cholesterol and higher alkaline phosphatase were marginal predictors. CONCLUSIONS: Half of our HD patients had VC. Territories of radial, iliac, femoral and digital arteries were roughly equally affected, and 25% of patients had a calcification considered as severe. Older age was the only significant predicting variable for VC, with low HDL cholesterol and high alkaline phosphatase as marginal predictors. PMID- 24211753 TI - Longitudinal analysis of participants in the KEEP Mexico's chronic kidney disease screening program. AB - BACKGROUND AND AIMS: The Kidney Early Evaluation Program (KEEP) is a free screening and educational program aimed at detecting chronic kidney disease (CKD) among adult individuals who are at high-risk (those with diabetes, hypertension, or family history of these conditions or CKD). Confirmation of CKD diagnosis requires persistence of albuminuria or estimated GFR <60 mL/min for at least 3 months. We undertook this study to determine in a follow-up KEEP done at least 1 year after a baseline KEEP the following: 1) CKD incidence among individuals who initially tested negative for CKD, 2) transitions between CKD stages among individuals who initially tested positive for CKD. METHODS: A random sample of KEEP participants was invited to participate in a follow-up KEEP between 2008 and 2010. Paired analyses were conducted to compare CKD stages between baseline and follow-up KEEP. RESULTS: A total of 434 individuals with a mean age of 49 years and 77% females participated in the study. Overall CKD prevalence in the baseline KEEP was 24%, and most patients were unaware of the diagnosis. In the follow-up KEEP, CKD incidence was 14%. The percentage of patients who tested positive for CKD in the baseline KEEP and who remained positive regardless of stage in the follow-up KEEP was 40% for those with stage 1 at baseline, 52% for those with stage 2, 65% for those with stage 3, and 100% for those with stages 4 or 5. CONCLUSIONS: Screening for CKD among high-risk individuals is uncommon. KEEP is an effective program for detecting CKD. PMID- 24211754 TI - De novo development of heart valve calcification in incident peritoneal dialysis patients. AB - BACKGROUND AND AIMS: Cardiac valve calcification (VC) is a frequent complication in chronic kidney disease and is considered a risk factor for all-cause and cardiovascular mortality. However, little is known about the pathophysiology mechanisms that originate it and the factors associated with its development. We undertook this study to analyze the frequency and factors related to de novo development of mitral valve calcification (MVC) and aortic valve calcifications (AVC) in incident peritoneal dialysis (PD) patients. METHODS: A prospective cohort of 124 incident PD patients was studied. Demographic and clinical data were recorded and blood assayed at baseline and after 1 year of follow-up for calcium, phosphorus, glucose, urea, creatinine, cholesterol, triglycerides by spectrophotometry assay; high-sensitivity C-reactive protein (CRP) by immunoturbidimetric ultrasensitive assay, intact parathormone (iPTH) and osteocalcin by electrochemiluminescence, fetuin-A and osteoprotegerin by EDI ELISA. Valve calcification was evaluated by M-mode bidimensional echocardiogram. RESULTS: Sixty eight percent of patients were male, ages 43 +/- 13 years; 51% were diabetic with 1.4 +/- 1 months on PD. After 12.3 +/- 1 months, 57 patients (46%) developed VC: AVC in 33 (57.8%), MVC in 15 (26.3%) and 9 (15.8%) patients in both valves. There was no correlation between AVC and MCV. In univariate logistic regression analysis, age, diabetes and elevated concentrations of OPG, iPTH and CRP were risk factors for development MVC. In multivariate analysis, only iPTH remained an independent risk factor as was also the case in AVC. CONCLUSIONS: Age, diabetes, osteoprotegerin, parathormone and C-reactive protein are risk factors related to de novo development of MVC and iPTH for AVC in incident dialysis patients. PMID- 24211755 TI - Identifying undetected cases of chronic kidney disease in Mexico. Targeting high risk populations. AB - BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a major public health problem in Mexico. Current guidelines recommend routine CKD testing in patients at increased risk for CKD. We undertook this study to examine the diagnostic yield of targeted screening (case-finding) for CKD in high-risk populations in rural and urban communities in Jalisco, Mexico. METHODS: In a cross-sectional study, we did laboratory tests searching for CKD and its risk factors and compared the characteristics of participants with those reported by the National Health and Nutrition Survey 2006 (NHNS). Individuals who were aware that they had CKD and those <18 years of age were excluded. RESULTS: There were 9,169 participants assessed: 28.7% were men and mean age was 55.6 +/- 13.7 years. They were predominantly female (71.3 vs. 55.6%, p = 0.0001) and older (55.59 +/- 0.1 vs. 42.5 +/- 0.3 years, p = 0.0001) than the NHNS population. Self-reported diabetes (41.9 vs. 7.3%, p = 0001) and fasting blood sugar >126 mg/dl (56.1 vs. 14.4%, p = 0.0001) were more prevalent among the participants; self-reported hypertension (41.9 vs. 7.3%, p = 0.0001), systolic blood pressure >= 140 mm Hg or diastolic blood pressure >= 90 mm Hg (52.5 vs. 43.2%, p = 0.0001), and obesity (42.8. vs. 29.3%, p = 0.0001) were also more frequent among participants. There were 19.7% with proteinuria; CKD was more prevalent among the high risk participants in our study (31.3 vs. 8.0%, p = 0.0001) than in the general population. CONCLUSIONS: CKD was detected frequently in high-risk Mexican populations. Trials of case-finding and intervention are feasible and warranted in Mexico. PMID- 24211756 TI - Metabolic syndrome in children with chronic kidney disease: PON1 and treatment modality. AB - BACKGROUND AND AIMS: We undertook this study to evaluate the relationship between PON1, SOD and metabolic syndrome (MetS) in pediatric patients undergoing peritoneal dialysis, hemodialysis and patients in early stages of CKD. METHODS: We carried out an analytical cross-sectional study of 134 children 6-17 years old. We registered anthropometric variables, vital signs, basic biochemical parameters, intact PTH (iPTH), high sensitivity CRP (hs-CRP), paraoxonase-1; SOD; PON1/HDL-cholesterol and homocysteine. For statistical analyses we used t test, Mann Whitney U test, chi(2), Fisher exact test, linear or logistic regression models, using SPSS v.16.0. p values <0.05 were considered as significant. RESULTS: There were 66 (49.3%) females; 39 (29.1%) had CKD stages 2-4 (predialysis), 42 (31.3%) on hemodialysis (HD) and 53 (39.6%) on automated peritoneal dialysis (PD). Time from diagnosis was 26 months. Significant differences were observed in mean, systolic and diastolic blood pressure, C peptide, triglycerides, and HDL-cholesterol as well as PON1/HDL-cholesterol ratio and SOD. CONCLUSIONS: This study demonstrates that PON1 and SOD may be predictors for the presence of MetS in pediatric patients under treatment with peritoneal dialysis. The positive correlation observed in PON1/HDL-cholesterol ratio may reflect the protector effect of HDL-cholesterol in patients with CKD according with the modality of treatment. PMID- 24211757 TI - Practice budgets and the patient mix of physicians - the effect of a remuneration system reform on health care utilisation. AB - This study analyses the effect of a change in the remuneration system for physicians on the treatment lengths as measured by the number of doctor visits using data from the German Socio-Economic Panel over the period 1995-2002. Specifically, I analyse the introduction of a remuneration cap (so called practice budgets) for physicians who treat publicly insured patients in 1997. I find evidence that the reform of 1997 did not change the extensive margin of doctor visits but strongly affected the intensive margin. The conditional number of doctor visits among publicly insured decreased while it increased among privately insured. This can be seen as evidence that physicians respond to the change in incentives induced by the reform by altering their patient mix. PMID- 24211758 TI - Testing the rate of preference reversal in personal and social decision-making. AB - Classic preference reversal, where choice and valuation procedures generate inconsistent preference orderings, has rarely been tested in hypothetical health care treatment scenarios. Two studies - the first non-incentivised and the second incentivised - are reported in this article. In both studies, respondents are asked to make decisions that affect themselves (a personal decision making frame) and those for whom they are responsible (a social decision making frame). The results show non-negligible and systematic rates of preference reversal in both frames, although these rates are slightly, but non-significantly, lower in the incentivised condition. Moreover, in both studies, the rate of predicted preference reversal was somewhat higher in the social than in the personal decision making frame, a finding that is explained by greater risk aversion when choosing treatment options for others than when choosing treatments for oneself. PMID- 24211759 TI - Systemic rhabdomyolysis induced by venom of freshwater stingrays Plesiotrygon iwamae and Potamotrygon motoro (Chondrichthyes-Potamotrygonidae) from the Amazon Basin. AB - Injuries caused by freshwater stingrays are characterized by intense pain and pathological changes at the lesion site, including oedema, erythema and, in most cases, necrosis. In this study, the systemic myotoxic activity induced by mucus extracts from the dorsal region and stinger of the stingrays Plesiotrygon iwamae and Potamotrygon motoro was described, analysed and quantified. Twenty-four hours after injection of 400 MUg of the extracts into the gastrocnemius muscle of mice, the following effects were observed: coagulative necrosis of the muscle tissue, muscle fibre regeneration and the presence of inflammatory infiltrates, including neutrophils, macrophages, and a reduced number of eosinophils and lymphocytes. These changes were also observed, although to a lesser extent, in the gastrocnemius muscles of the contralateral limbs, demonstrating that the extracts from the two species could induce systemic rhabdomyolysis. Based on morphometric analysis, it was observed that the stinger extract of P. motoro was more potent in inducing local and systemic myotoxic activity, followed by the dorsal extract from P. motoro and stinger and dorsal extracts from P. iwamae, which induced similar effects. PMID- 24211760 TI - DNA microarray analysis on gene candidates possibly related to tetrodotoxin accumulation in pufferfish. AB - Pufferfish accumulate tetrodotoxin (TTX) at high levels in liver and ovary through the food chain. However, the mechanisms underlying TTX toxification in pufferfish have been poorly understood. In order to search gene candidates involved in TTX accumulation in the torafugu pufferfish Takifugu rubripes, a custom 4x44k oligonucleotide microarray slide was designed by the Agilent eArray program using oligonucleotide probes of 60 bp in length referring to 42,724 predicted transcripts in the publicly available Fugu genome database. DNA microarray analysis was performed with total RNA samples from the livers of two toxic wild specimens in comparison with those from a nontoxic wild specimen and two nontoxic cultured specimens. The mRNA levels of 1108 transcripts were more than 2-fold higher in the toxic specimens than in the nontoxic specimens. The levels of 613 transcripts were remarkably high, and 16 transcripts encoded by 9 genes were up-regulated more than 10-fold. These genes included those encoding forming structural filaments (keratins) and those related to vitamin D metabolism and immunity. It was also noted that the levels of the transcripts encoding serpin peptidase inhibitor clade C member 1, coagulation factor X precursor, complement C2, C3, C5, C8 precursors, and interleukin-6 receptor were high in the toxic liver samples. PMID- 24211761 TI - Do the BEAF insulator proteins regulate genes involved in cell polarity and neoplastic growth? AB - It was reported that a chromosome with the BEAF(NP6377) (NP6377) allele leads to a loss of cell polarity and neoplastic growth in Drosophila melanogaster when homozygous (Gurudatta et al., 2012). We had previously generated the BEAF(AB-KO) (AB-KO) allele by homologous recombination and did not note these phenotypes (Roy et al., 2007). Both alleles are null mutations. It was unclear why two null alleles of the same gene would give different phenotypes. To resolve this, we performed genetic tests to explore the possibility that the chromosome with the NP6377 allele contained other, second site mutations that might account for the different phenotypes. We found that the chromosome with NP6377 has at least two additional mutations. At least one of these, possibly in combination with the NP6377 allele, is presumably responsible for the reported effects on gene expression, cell polarity and neoplastic growth. PMID- 24211762 TI - Interactions between lens epithelial and fiber cells reveal an intrinsic self assembly mechanism. AB - How tissues and organs develop and maintain their characteristic three dimensional cellular architecture is often a poorly understood part of their developmental program; yet, as is clearly the case for the eye lens, precise regulation of these features can be critical for function. During lens morphogenesis cells become organized into a polarized, spheroidal structure with a monolayer of epithelial cells overlying the apical tips of elongated fiber cells. Epithelial cells proliferate and progeny that shift below the lens equator differentiate into new fibers that are progressively added to the fiber mass. It is now known that FGF induces epithelial to fiber differentiation; however, it is not fully understood how these two forms of cells assemble into their characteristic polarized arrangement. Here we show that in FGF-treated epithelial explants, elongating fibers become polarized/oriented towards islands of epithelial cells and mimic their polarized arrangement in vivo. Epithelial explants secrete Wnt5 into the culture medium and we show that Wnt5 can promote directed behavior of lens cells. We also show that these explants replicate aspects of the Notch/Jagged signaling activity that has been shown to regulate proliferation of epithelial cells in vivo. Thus, our in vitro study identifies a novel mechanism, intrinsic to the two forms of lens cells, that facilitates self assembly into the polarized arrangement characteristic of the lens in vivo. In this way the lens, with its relatively simple cellular composition, serves as a useful model to highlight the importance of such intrinsic self-assembly mechanisms in tissue developmental and regenerative processes. PMID- 24211763 TI - Oxidative stress precedes mitochondrial dysfunction in gerbil brain after aluminum ingestion. AB - Several studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer disease. The dynamic of changes in acetylcholinesterase (AChE), cytochrome c oxidase (COX), Complex I, superoxide dismutase (SOD) and catalase (CAT) activities, and the lipid peroxide (MDA), superoxide anion (O2(-)) and thiol (SH) group levels in gerbil's brain after aluminum ingestion were analyzed. Gerbils that orally received aluminum chloride (LD25 or LD50) were sacrificed 2, 6 or 24 h later. Another group was subacutely treated (21 days; LD10). Controls received saline. Biochemical parameters were measured in cortex, hippocampus, thalamus and nucleus caudatus. Two hours after acute Al exposure AChE activity and SH group content were decreased and MDA and O2(-) levels were elevated in all investigated brain structures. The changes of COX and CAT were structure specific. SOD was increased after 6 h. Changes of investigated parameters were also seen after subacute Al treatment. These results might suggest the presence of additional source of free radicals in early phase of Al poisoning. PMID- 24211764 TI - The protective effect of melatonin and S-methylisothiourea treatments in nitrogen mustard induced lung toxicity in rats. AB - OBJECTIVES: Mustard is highly toxic to the lung. Its toxic effects are associated with inflammatory cell accumulation and increased pro-inflammatory cytokines as well as reactive oxygen and nitrogen species. In this study, we aimed to investigate the efficiency of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced lung toxicity. METHODS: Thirty-six male rats were randomly divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Control group was given saline only via transdermal route. Other groups were exposured to a single dose of MEC (3.5 mg/kg) via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: MEC injection resulted in alveolar epithelial injury, hemorrhage, inflammation, edema and interalveolar septal thickening in the lung tissues. The tissue TNF alpha, IL-1beta, and nitrate/nitrite (NOx) levels were found significantly different for all groups (p<0.001). TNF-alpha and IL-1beta levels increased significantly with MEC exposure, and MEL and SMT ameliorated these increases in lung tissues. MEC also elevated NOx levels in lung tissue. Melatonin showed meaningful protection against lung injury. But protection of SMT was weaker. CONCLUSION: Inflammation plays an important role in the MEC induced lung toxicity as well as oxidative and nitrosative stress. Melatonin has also anti-inflammatory properties similar to SMT, as well as anti-oxidant properties. But melatonin treatment was found more efficient than SMT treatment. PMID- 24211765 TI - Total salivary nitrates and nitrites in oral health and periodontal disease. AB - It is well known that nitrites are increased in saliva from patients with periodontal disease. In the oral cavity, nitrites may derive partly from the reduction of nitrates by oral bacteria. Nitrates have been reported as a defence related mechanism. Thus, the aim of the present study was to determine the salivary levels of total nitrate and nitrite and their relationship, in unstimulated and stimulated saliva from periodontal healthy subjects, and from patients with chronic periodontal disease. Nitrates and nitrites were determined in saliva from thirty healthy subjects and forty-four patients with periodontal disease. A significant increase in salivary nitrates and nitrites was observed. Nitrates and nitrites concentration was related to clinical attachment level (CAL). A positive and significant Pearson's correlation was found between salivary total nitrates and nitrites. Periodontal treatment induced clinical improvement and decreased nitrates and nitrites. It is concluded that salivary nitrates and nitrites increase, in patients with periodontal disease, could be related to defence mechanisms. The possibility that the salivary glands respond to oral infectious diseases by increasing nitrate secretion should be explored further. PMID- 24211766 TI - Formation of distinct chromatin conformation signatures epigenetically regulate macrophage activation. AB - Microbial-lipopolysacharide (LPS), interleukin 4 (IL-4) and interferon gamma (IFN gamma) polarise macrophages into "innate", "alternative" and "classical", activation states by selective gene regulation. Expression of MARCO, CD200, CD200R1 (innate), MRC1 (alternative) and H2-Eb1 (classical) selectively marks these distinct activation states. Epigenetic events drive such activation upon stimuli and here we study one such mechanism, chromatin conformation signatures implicated in long-range chromatin interactions that regulate transcriptional switch and gene expression. The EpiSwitchTM technology was used to identify and analyse potential markers bordering such conformational signatures for these genes and juxtaposition of markers was compared between resting and activated macrophages. LPS, IL-4 and IFN-gamma selectively altered chromatin conformations of their responsive genes in wild type, but not in MyD88(-/-), IL-4R(-/-) and IFN gammaR(-/-) macrophages. In addition, two distinct conformations were observed in CD200R1 after LPS and IFN-gamma stimulation. In summary, signal-specific alterations in chromatin conformation provide biomarkers that identify and determine distinct gene expression programmes during macrophage activation. PMID- 24211767 TI - Quantitative accuracy in mass spectrometry based proteomics of complex samples: the impact of labeling and precursor interference. AB - Knowing the limit of quantification is important to accurately judge the results from proteomics studies. In order to investigate isobaric labels in combination with peptide pre-fractionation by high resolution isoelectric focusing in terms of limit of detection, quantitative accuracy and how to improve it, we used a human cell lysate spiked with 57 protein standards providing reference points across a wide concentration range. Specifically, the impact of precursor mixing (isolation interference and reporter ion interference) on quantitative accuracy was investigated by co-analyzing iTRAQ (8-plex) and TMT (6-plex) labeled peptides. A label-free analysis was also performed. Peptides, labeled or label free, were analyzed by LC-MS/MS (Orbitrap Velos). We identified 3386 proteins by the label-free approach, 4466 with iTRAQ and 5961 with TMT. A linear range of quantification down to 1fmol was indicated for both isobaric and label-free analysis workflows, with an upper limit exceeding 60fmol. Our results indicate that 6-plex TMT is more sensitive than 8-plex iTRAQ. For isobaric labels, quantitative accuracy was affected by precursor mixing. Based on our evaluation on precursor mixing and accuracy of isobaric label quantification, we propose a cut off of <30% isolation interference for peptide spectrum matches (PSMs) used in the quantification. BIOLOGICAL SIGNIFICANCE: Quantitative proteome analysis by mass spectrometry offers opportunities for biological research. However, knowing the limit of quantification in biological samples is important to accurately judge the results. By using a high-complexity sample spiked with protein standards of known concentrations, we investigated the quantification limits of label-free and label-based peptide quantification, including an evaluation of precursor mixing and its impact on quantification accuracy by isobaric labels. We suggest limits of allowed precursor interference and believe that this study contributes with information useful in proteome quantification by mass spectrometry. PMID- 24211768 TI - Hemotoxicity of carbon nanotubes. AB - Carbon nanotubes may enter into the bloodstream and interact with blood components indirectly via translocation following unintended exposure or directly after an intended administration for biomedical purposes. Once introduced into systemic circulation, nanotubes will encounter various proteins, biomolecules or cells which have specific roles in the homeostasis of the circulatory system. It is therefore essential to determine whether those interactions will lead to adverse effects or not. Advances in the understanding of how carbon nanotubes interact with blood proteins, the complement system, red blood cells and the hemostatic system are reviewed in this article. While many studies on carbon nanotube health risk assessment and their biomedical applications have appeared in the last few years, reports on the hemocompatibility of these nanomaterials remain surprisingly limited. Yet, defining the hemotoxicological profile is a mandatory step toward the development of clinically-relevant medications or contrast agents based on carbon nanotubes. PMID- 24211769 TI - Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. AB - The in vitro mammalian cytogenetic tests monitor chromosomal aberrations in cultured mammalian cells to test the mutagenicity of compounds. Although these tests are especially useful for evaluating the potential clastogenic effects of chemicals, false positives associated with excessive toxicity occur frequently. There is a growing demand for mechanism-based assays to confirm positive results from cytogenetic tests. We hypothesized that a toxicogenomic approach that is based on gene expression profiles could be used to investigate mechanisms of genotoxicity. Human lymphoblastoid TK6 cells were treated with each of eight different genotoxins that included six DNA damaging compounds-mitomycin C, methyl methanesulfonate, ethyl methanesulfonate, cisplatin, etoposide, hydroxyurea-and two compounds that do not damage DNA-colchicine and adenine. Cells were exposed to each compound for 4h, and Affymetrix U133A microarrays were then used to comprehensively examine gene expression. A statistical analysis was used to select biomarker candidates, and 103 probes met our statistical criteria. Expression of cyclin-dependent kinase inhibitor 1A (CDKN1A)/p21 was ranked highest for discriminating DNA-damaging compounds. To further characterize the biological significance of alterations in gene expression, functional network analysis was performed with the 103 selected probes. Interestingly, a CDKN1A centered interactome was identified as the most significant network. Together, these findings indicated that DNA-damaging compounds often induced changes in the expression of a large number of these 103 probes and that upregulation of CDKN1A was a common key feature of DNA damage stimuli. The utility of CDKN1A as a biomarker for assessing the genotoxicity of drug candidates was further evaluated; specifically, quantitative RT-PCR was used to assess the effects of 14 additional compounds-including DNA damaging genotoxins and genotoxins that do not damage DNA and five newly-synthesized drug candidates-on CDKN1A expression. In these assays, DNA damage-positive clastogens were clearly separated from DNA damage-negative compounds based on CDKN1A expression. In conclusion, CDKN1A may be a valuable biomarker for identifying DNA damage-inducing clastogens and as a follow-up assay for mammalian cytogenetic tests. PMID- 24211770 TI - Statistical approaches to maximize recombinant protein expression in Escherichia coli: a general review. AB - The supply of many valuable proteins that have potential clinical or industrial use is often limited by their low natural availability. With the modern advances in genomics, proteomics and bioinformatics, the number of proteins being produced using recombinant techniques is exponentially increasing and seems to guarantee an unlimited supply of recombinant proteins. The demand of recombinant proteins has increased as more applications in several fields become a commercial reality. Escherichia coli (E. coli) is the most widely used expression system for the production of recombinant proteins for structural and functional studies. However, producing soluble proteins in E. coli is still a major bottleneck for structural biology projects. One of the most challenging steps in any structural biology project is predicting which protein or protein fragment will express solubly and purify for crystallographic studies. The production of soluble and active proteins is influenced by several factors including expression host, fusion tag, induction temperature and time. Statistical designed experiments are gaining success in the production of recombinant protein because they provide information on variable interactions that escape the "one-factor-at-a-time" method. Here, we review the most important factors affecting the production of recombinant proteins in a soluble form. Moreover, we provide information about how the statistical design experiments can increase protein yield and purity as well as find conditions for crystal growth. PMID- 24211771 TI - Purification and biological characterization of soluble, recombinant mouse IFNbeta expressed in insect cells. AB - Interferon beta (IFNbeta) is a member of the type I interferon family of cytokines widely recognised for their anti-viral, anti-proliferative and immunomodulatory properties. Recombinant, biologically active forms of this cytokine are used clinically for the treatment of multiple sclerosis and in laboratories to study the role of this cytokine in health and disease. Established methods for expression of IFNbeta utilise either bacterial systems from which the insoluble recombinant proteins must be refolded, or mammalian expression systems in which large volumes of cell culture are required for recovery of acceptable yields. Utilising the baculovirus expression system and Trichoplusia ni (Cabbage Looper) BTI-TN-5B1-4 cell line, we report a reproducible method for production and purification of milligram/litre quantities of biologically active murine IFNbeta. Due to the design of our construct and the eukaryotic nature of insect cells, the resulting soluble protein is secreted allowing purification of the Histidine-tagged natively-folded protein from the culture supernatant. The IFNbeta purification method described is a two-step process employing immobilised metal-ion affinity chromatography (IMAC) and reverse-phase high performance liquid chromatography (RP-HPLC) that results in production of significantly more purified IFNbeta than any other reported eukaryotic-based expression system. Recombinant murine IFNbeta produced by this method was natively folded and demonstrated hallmark type I interferon biological effects including antiviral and anti-proliferative activities, and induced genes characteristic of IFNbeta activity in vivo. Recombinant IFNbeta also had specific activity levels exceeding that of the commercially available equivalent. Together, our findings provide a method for production of highly pure, biologically active murine IFNbeta. PMID- 24211772 TI - Type of object motion facilitates word mapping by preverbal infants. AB - This study assessed whether specific types of object motion, which predominate in maternal naming to preverbal infants, facilitate word mapping by infants. A total of 60 full-term 8-month-old infants were habituated to two spoken words, /baef/ and /wem/, synchronous with the handheld motions of a toy dragonfly and a fish or a lamb chop and a squiggly. They were presented in one of four experimental motion conditions-shaking, looming, upward, and sideways-and one all-motion control condition. Infants were then given a test that consisted of two mismatch (change) and two control (no-change) trials, counterbalanced for order. Results revealed that infants learned the word-object relations (i.e., looked longer on the mismatch trials relative to the control trials) in the shaking and looming motion conditions but not in the upward, sideways, and all-motion conditions. Infants learned the word-object relations in the looming and shaking conditions likely because these motions foreground the object for the infants. Thus, the type of gesture an adult uses matters during naming when preverbal infants are beginning to map words onto objects. The results suggest that preverbal infants learn word-object relations within an embodied system involving matches between infants' perception of motion and specific motion properties of caregivers' naming. PMID- 24211773 TI - Antifungal and antiaflatoxigenic properties of Cuminum cyminum (L.) seed essential oil and its efficacy as a preservative in stored commodities. AB - The study reports potential of Cuminum cyminum (cumin) seed essential oil (EO) as a plant based shelf life enhancer against fungal and aflatoxin contamination and lipid peroxidation. The EO showed efficacy as a preservative in food systems (stored wheat and chickpeas). A total of 1230 fungal isolates were obtained from food samples, with Aspergillus flavus LHP(C)-D6 identified as the highest aflatoxin producer. Cumin seed EO was chemically characterized through GC-MS where cymene (47.08%) was found as the major component. The minimum inhibitory concentration and minimum aflatoxin inhibitory concentration of EO were 0.6 and 0.5 MUl/ml respectively. The EO showed toxicity against a broad spectrum of food borne fungi. The antifungal action of EO on ergosterol content in the plasma membrane of A. flavus was determined. The EO showed strong antioxidant potential having IC50 0.092 MUl/ml. As a fumigant in food systems, the EO provided sufficient protection of food samples against fungal association without affecting seed germination. In view of the antifungal and antiaflatoxigenic nature, free radical scavenging potential and efficacy in food system, cumin seed EO may be able to provide protection of food commodities against quantitative and qualitative losses, thereby enhancing their shelf life. The present investigation comprises the first report on antifungal mode of action of cumin seed EO and its efficacy as fumigant in food systems. PMID- 24211774 TI - Extended spectrum beta-lactamase- and constitutively AmpC-producing Enterobacteriaceae on fresh produce and in the agricultural environment. AB - The attribution of fresh produce to the overall community-associated exposure of humans to ESBL- or AmpC-producing bacteria is currently unknown. To address this issue, the prevalence of ESBL- and AmpC-producing Enterobacteriaceae on fresh produce produced in the Netherlands was determined. Seven vegetable types that are consumed raw were selected: blanched celery, bunched carrots, chicory, endive, iceberg lettuce, mushrooms, and radish. The vegetables were mostly obtained from supermarkets. To determine whether the agricultural environment is the source of ESBL-producing Enterobacteriaceae on fresh produce, iceberg lettuce was also obtained directly from three farms, in conjunction with soil and irrigation water. ESBL-producing Enterobacteriaceae isolated from vegetables and environment were all environmental species: Rahnella aquatilis (n = 119), Serratia fonticola (n = 45) and Pantoea agglomerans (n = 1). ESBL genes of R. aquatilis and S. fonticola were identified as blaRAHN-1 and blaRAHN-2 and blaFONA 1, blaFONA-2, blaFONA-3/6 and blaFONA-5, respectively. For R. aquatilis and S. fonticola, different prevalence numbers were observed using different isolation methods, which could at least partially be explained by an inverse correlation between the level of cefotaxime resistance of these species and incubation temperature. R. aquatilis was isolated from 0 to 46% of soil samples and 11 to 83% of vegetable samples, and S. fonticola from 2 to 60% of soil samples and 0 to 1.3% of vegetable samples. Third generation cephalosporin-resistant faecal Enterobacteriaceae were isolated from 2.7%, 1.3% and 1.1% of supermarket vegetables, iceberg lettuce from farms, and agricultural soil respectively. Faecal Enterobacteriaceae were all identified as Citrobacter and Enterobacter species and, with the exception of one Citrobacter koseri strain, all had phenotypes indicative of constitutive AmpC production. Comparison of fresh produce and its agricultural environment indicates that the Enterobacteriaceae population on fresh produce reflects that of the soil it is grown in. Public health risks associated with exposure to ESBL- and AmpC-producing bacteria through consumption of uncooked fresh produce are diverse. They range from occasional ingestion of 3GC-resistant opportunistic pathogens which may result in difficult-to-treat infections, to frequent ingestion of relatively harmless ESBL producing environmental bacteria that may therewith constitute a continuously replenished intestinal reservoir facilitating dissemination of ESBL genes to (opportunistic) pathogens. PMID- 24211775 TI - Antifungal impact of volatile fractions of Peumus boldus and Lippia turbinata on Aspergillus section Flavi and residual levels of these oils in irradiated peanut. AB - To investigate the antifungal properties of essential oil (EO) vapors from boldo and poleo on Aspergillus section Flavi and the residual levels of the oils in peanut, irradiated peanuts conditioned at three water activities (0.98, 0.95, 0.93) were treated with 2 and 3 MUL/g of boldo and 3 and 5 MUL/g of poleo. EO treatments produced the greatest impact on fungal growth parameters, followed by oil concentrations and aW levels. The three main components in peanut exposed to oil vapors were piperitone oxide, alpha-terpinene and eucalyptol for boldo and beta-caryophyllene epoxide, limonene and piperitenone for poleo. Residues of boldo and poleo EO were significantly decreased from 24.7 to 100% and from 26.6 to 99.7% at the end of the incubation period, respectively. The application of nontoxic boldo oil as fumigant in the control of Aspergillus section Flavi may represent a potential alternative antifungal treatment, without significant residues after 35 days. PMID- 24211776 TI - Successful construction and stable expression of an anti-CD45RA scFv-EGFP fusion protein in Chinese hamster ovary cells. AB - CD45RA has been found highly expressed on leukemia cells and may be a potential target of the disease. In this study, an anti-CD45RA single-chain antibody fragment (scFv3A4) was genetically linked to the N terminus of the enhanced green fluorescent protein (EGFP) to generate a scFv3A4-EGFP fusion protein. The scFv3A4 EGFP with a molecular weight of 57kDa was stably expressed and secreted from the transfected CHO cells through the ER/Golgi-dependent pathway. The fusion protein was soluble in the culture supernatant and the yield was 1350MUg/L. Flow cytometry analysis showed that the scFv3A4-EGFP had the same binding site and a very similar reactivity pattern with its parental murine monoclonal antibody (mAb) 3A4. Furthermore, comparing to conventional labeled 3A4-FITC antibody, the scFv3A4-EGFP was more resistant to illumination and more suitable for immunofluorescence histology (IFH) detection. Therefore, the scFv3A4-EGFP fusion protein can be a powerful tool to investigate the targeting of CD45RA on leukemia cells, biological activity of the target and possibly for the genetic manipulation of the antibody. PMID- 24211777 TI - Tyrosine decarboxylase from Lactobacillus brevis: soluble expression and characterization. AB - Tyrosine decarboxylase (TDC, EC 4.1.1.25) is an enzyme that catalyzes the decarboxylation of l-tyrosine to produce tyramine and CO2. In this study, a 1881 bp tdc gene from Lactobacillus brevis was cloned and heterologously expressed in Escherichia coli BL21 (DE3). Glucose was discovered to play an important role in the soluble expression of rLbTDC. After optimization, recombinant TDC (rLbTDC) was achieved in excellent solubility and a yield of 224mg rLbTDC/L broth. The C terminal His-Tagged rLbTDC was one-step purified with 90% recovery. Based on SDS PAGE and gel filtration analysis, rLbTDC is a dimer composed of two identical subunits of approximately 70kDa. Using l-tyrosine as substrate, the specific activity of rLbTDC was determined to be 133.5U/mg in the presence of 0.2mM pyridoxal-5'-phosphate at 40 degrees C and pH 5.0. The Km and Vmax values of rLbTDC were 0.59mM and 147.1MUmolmin(-1)mg(-1), respectively. In addition to l tyrosine, rLbTDC also exhibited decarboxylase activity towards l-DOPA. This study has demonstrated, for the first time, the soluble expression of tdc gene from L. brevis in heterologous host. PMID- 24211778 TI - Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-D-aspartate receptor in aged rats. AB - AIMS: Pain may be associated with postoperative cognitive dysfunction (POCD); however, this relationship remains under investigated. Therefore, we examined the impact of postoperative pain on cognitive functions in aged animals. MAIN METHODS: Rats were allocated to the following groups: control (C), 1.2 % isoflurane for 2 hours alone (I), I with laparotomy (IL), IL with analgesia using local ropivacaine (IL+R), and IL with analgesia using systemic morphine (IL+M). Pain was assessed by rat grimace scale (RGS). Spatial memory was evaluated using a radial maze from postoperative days (POD) 3 to 14. NMDA receptor (NR) 2 subunits in hippocampus were measured by ELISA. Finally, effects of memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on postoperative cognitive performance were tested. KEY FINDINGS: Postoperative RGS was increased in Group IL, but not in other groups. The number of memory errors in Group I were comparable to that in Group C, whereas errors in Group IL were increased. Importantly, in Group IL+R and IL+M, cognitive impairment was not found. The memory errors were positively correlated with the levels of NMDA receptor 2 subunits in hippocampus. Prophylactic treatment with memantine could prevent the development of memory deficits observed in Group IL without an analgesic effect. SIGNIFICANCE: Postoperative pain contributes to the development of memory deficits after anesthesia and surgery via up-regulation of hippocampal NMDA receptors. Our findings suggest that postoperative pain management may be important for the prevention of POCD in elderly patients. PMID- 24211779 TI - Disruption of endothelial adherens junction by invasive breast cancer cells is mediated by reactive oxygen species and is attenuated by AHCC. AB - AIMS: The effect of antioxidants on treatment of cancer is still controversial. Previously, we demonstrated that interaction of breast cancer cells with endothelial cells leads to tyrosine phosphorylation of VE-cadherin and disruption of endothelial adherens junction (EAJ). The molecular mechanism underlying the anti-metastatic effects of mushroom-derived active hexode correlated compound (AHCC) remains elusive. MAIN METHODS: Several cellular and biochemical techniques were used to determine the contribution of oxidative stress in the disruption of EAJ and to test this hypothesis that AHCC inhibits the breast cancer cell-induced disruption of EAJ. KEY FINDINGS: Interaction of breast cancer cells (MDA-MB-231 cells) with human umbilical vein endothelial cells (HUVECs) leads to an increase in generation of reactive oxygen species (ROS). Treatment of HUVECs with H2O2 or phorbol myristate acetate (PMA) led to tyrosine phosphorylation of VE-cadherin, dissociation of beta-catenin from VE-cadherin complex and increased transendothelial migration (TEM) of MDA-MB-231 cells. Induction of VE-cadherin tyrosine phosphorylation by PMA or by interaction of MDA-MB-231 cells with HUVECs was mediated by HRas and protein kinase C-alpha signaling pathways. Disruption of EAJ and phosphorylation of VE-cadherin induced by interaction of MDA-MB-231 cells with HUVECs were attenuated when HUVECs were pretreated with an antioxidant, N acetylcysteine (NAC) or AHCC. AHCC inhibited TEM of MDA-MB-231 cells and generation of ROS induced by interaction of MDA-MB-231 cells with HUVECs. SIGNIFICANCE: Our studies suggest that ROS contributes to disruption of EAJ induced by interaction of MDA-MB-231 cells with HUVECs and AHCC attenuates this alteration. PMID- 24211780 TI - Inhibitory effects of pitavastatin on fibrogenic mediator production by human lung fibroblasts. AB - AIMS: Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3 methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). MAIN METHODS: NHLF were pretreated with 100nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-beta1 (TGF-beta1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. KEY FINDINGS: TGF-beta1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C-X-C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. SIGNIFICANCE: Pitavastatin appeared to inhibit TGF-beta1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin. PMID- 24211781 TI - Dynamic modulation of epileptic high frequency oscillations by the phase of slower cortical rhythms. AB - Pathological high frequency oscillations (pHFOs) have been proposed to be robust markers of epileptic cortex. Oscillatory activity below this frequency range has been shown to be modulated by phase of lower frequency oscillations. Here, we tested the hypothesis that dynamic cross-frequency interactions involving pHFOs are concentrated within the epileptogenic cortex. Intracranial electroencephalographic recordings from 17 children with medically-intractable epilepsy secondary to focal cortical dysplasia were obtained. A time-resolved analysis was performed to determine topographic concentrations and dynamic changes in cross-frequency amplitude-to-phase coupling (CFC). CFC between pHFOs and the phase of theta and alpha rhythms was found to be significantly elevated in the seizure-onset zone compared to non-epileptic regions (p<0.01). Data simulations showed that elevated CFC could not be attributed to the presence of sharp transients or other signal properties. The phase of low frequency oscillations at which pHFO amplitudes were maximal was inconsistent at seizure initiation, yet consistently at the trough of the low frequency rhythm at seizure termination. Amplitudes of pHFOs were most significantly modulated by the phase of alpha-band oscillations (p<0.01). These results suggest that increased CFC between pHFO amplitude and alpha phase may constitute a marker of epileptogenic brain areas and may be relevant for understanding seizure dynamics. PMID- 24211782 TI - Nuclear localization of bradykinin B(2) receptors reflects binding to the nuclear envelope protein lamin C. AB - The mechanism of action of bradykinin (BK), a pro-inflammatory mediator, is thought to be mediated by specific cell surface membrane bradykinin B2 receptors. Some evidence suggests that there are both intracellular and nuclear bradykinin B2 receptors. This study identified proteins that interact with the C-terminus of the bradykinin B2 receptor (in particular, the nuclear membrane protein lamin C), using the yeast two-hybrid system. The motif of the C-terminal domain (CT) mutant 303-320 in bradykinin B2 receptor was identified as a lamin C protein binding motif. Immunohistochemistry revealed colocalization of FLAG- bradykinin B2 receptor with HA-lamin C in the nucleus of HEK 293T cells. In situ proximity ligation assay (PLA) showed that FLAG-bradykinin B2 receptor formed heterodimers with HA-lamin C in the nucleus. In addition, live cell fluorescence imaging showed that bradykinin B2 receptor-EGFP was located in the nucleus and co localized with HcRed-lamin C. Interestingly, neither BK addition nor bradykinin B2 receptor CT mutation reduced the binding to lamin C or changed the distribution of bradykinin B2 receptor. Taken together, these findings demonstrate that bradykinin B2 receptor-lamin C heterodimers form in the nucleus independent of BK stimulation and CT mutation. We propose that heterodimerization of bradykinin B2 receptor with lamin C is essential to nuclear localization of bradykinin B2 receptor and plays an important role in cell signaling and function. PMID- 24211783 TI - Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study. AB - The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone. PMID- 24211784 TI - Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3beta and beta catenin pathway. AB - Neurogenesis in the adult dentate gyrus (DG) is decreased in rodent models for mood disorders. Mood stabilizers including lithium (Li) and valproate (VPA) increase it. These increasing effects of Li and VPA on neurogenesis in adult DG are considered to be one of the therapeutic actions of Li and VPA, but their molecular mechanism remains unclear. We have already reported that Li recovers the inhibitory effects of dexamethasone (DEX), an agonist of glucocorticoid receptor, on the proliferation of adult rat DG-derived neural precursor cells (ADP) via GSK-3beta and beta-catenin pathway. Following it, here we investigated the mechanism underlying the recovery effects of VPA on DEX-induced decrease of ADP proliferation. VPA is an inhibitor of histone deacetylase (HDAC). However, Trichostatin A, a HDAC inhibitor, had no effect on ADP proliferation. In contrast, SB415286, a specific GSK-3beta inhibitor, recovered DEX-induced decrease of ADP proliferation. In addition, quercetin (Que), a beta-catenin pathway inhibitor, abolished such a recovery effect of VPA. Moreover, nuclear beta-catenin and the expression of cyclin D1 were altered by DEX, VPA and Que like the proliferation. Moreover, VPA increased the phosphorylation of Ser(9), which is known as the inhibitory phosphorylation site of GSK-3beta. These suggest that HDAC is not involved in the recovery effect of VPA on ADP proliferation and that VPA recovers the inhibitory effects of DEX via increasing the phosphorylation of Ser(9) on GSK-3beta and following up-regulation of beta catenin pathway. Therefore, GSK-3beta and beta-catenin pathway might play a role in the increasing effects of VPA on neurogenesis on adult DG. PMID- 24211785 TI - Benzophenanthridine alkaloid, piperonyl butoxide and (S)-methoprene action at the cannabinoid-1 receptor (CB1-receptor) pathway of mouse brain: Interference with [(3)H]CP55940 and [(3)H]SR141716A binding and modification of WIN55212-2 dependent inhibition of synaptosomal l-glutamate release. AB - Benzophenanthridine alkaloids (chelerythrine and sanguinarine) inhibited binding of [(3)H]SR141716A to mouse brain membranes (IC50s: <1uM). Piperonyl butoxide and (S)-methoprene were less potent (IC50s: 21 and 63uM respectively). Benzophenanthridines and piperonyl butoxide were more selective towards brain CB1 receptors versus spleen CB2 receptors. All compounds reduced Bmax of [(3)H]SR141716A binding to CB1 receptors, but only methoprene and piperonyl butoxide increased Kd (3-5-fold). Benzophenanthridines increased the Kd of [(3)H]CP55940 binding (6-fold), but did not alter Bmax. (S)-methoprene increased the Kd of [(3)H]CP55940 binding (by almost 4-fold) and reduced Bmax by 60%. Piperonyl butoxide lowered the Bmax of [(3)H]CP55940 binding by 50%, but did not influence Kd. All compounds reduced [(3)H]SR141716A and [(3)H]CP55940 association with CB1 receptors. Combined with a saturating concentration of SR141716A, only piperonyl butoxide and (S)-methoprene increased dissociation of [(3)H]SR141716A above that of SR141716A alone. Only piperonyl butoxide increased dissociation of [(3)H]CP55940 to a level greater than CP55940 alone. Binding results indicate predominantly allosteric components to the study compounds action. 4 Aminopyridine-(4-AP-) evoked release of l-glutamate from synaptosomes was partially inhibited by WIN55212-2, an effect completely neutralized by AM251, (S) methoprene and piperonyl butoxide. With WIN55212-2 present, benzophenanthridines enhanced 4-AP-evoked l-glutamate release above 4-AP alone. Modulatory patterns of l-glutamate release (with WIN-55212-2 present) align with previous antagonist/inverse agonist profiling based on [(35)S]GTPgammaS binding. Although these compounds exhibit lower potencies compared to many classical CB1 receptor inhibitors, they may have potential to modify CB1-receptor-dependent behavioral/physiological outcomes in the whole animal. PMID- 24211786 TI - Baicalin inhibits Staphylococcus aureus-induced apoptosis by regulating TLR2 and TLR2-related apoptotic factors in the mouse mammary glands. AB - Baicalin, the major active constituent of the isolated root of Scutellaria baicalensis, is widely used in China and Southeast Asian countries. Evidence has indicated that baicalin has multiple biological activities, including anti apoptotic properties. Mastitis is a severe problem in humans and other animals and is characterized by mammary gland cell apoptosis. Staphylococcus aureus (S. aureus) is the major pathogen that causes mastitis. This study was designed to evaluate the protective effects of baicalin on the mammary glands during S. aureus-induced mastitis. In the present study, a mouse model was infected with S. aureus to induce mammary gland injury. Baicalin treatment was administered between 6 and 24h after infection. Toll-like receptor 2, p53, BAX, BCL-2 and caspase-3 expression were analyzed using qPCR and Western blotting. The results indicated that baicalin significantly attenuated pathological damage and cell death in the mammary glands. Further studies revealed that baicalin down regulated the expression of Toll-like receptor 2 (TLR2) and the phosphorylation of p53 in the mammary glands after S. aureus-induced mastitis. Baicalin also promoted the expression of BCL-2 at the mRNA and protein levels but inhibited BAX and caspase-3 (CASP-3) cleavage. Baicalin inhibited apoptosis and had protective effects on mammary gland tissues during S. aureus-induced mastitis. These effects were displayed by reductions in TLR2 expression and p53 phosphorylation and the regulation of apoptosis-related factors (BCL-2, BAX and CASP-3) in mammary gland tissues. PMID- 24211787 TI - Mechanism-driven phase I translational study of trifluoperazine in adults with sickle cell disease. AB - Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca(2+)/calmodulin protein kinase IIalpha (CaMKIIalpha) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIalpha inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10mg), we obtained 7-hourly and 24-h repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8+/-8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5h after the 10mg dose. The analgesic effect lasted for at least 24h in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1mg in repeated doses to determine long-term adverse and analgesic effects. PMID- 24211788 TI - Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model - a type II isobolographic analysis. AB - The aim of the presented study was to characterize the anticonvulsant effects of levetiracetam in combination with various antiepileptic drugs (carbamazepine, phenytoin, topiramate and vigabatrin) in the mouse 6Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32mA, 6Hz, 3s stimulus duration) delivered via ocular electrodes; type II isobolographic analysis was used to characterize the consequent anticonvulsant interactions between the various drug combinations for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. With type II isobolographic analysis, the combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.01) in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive. Levetiracetam combined with topiramate and vigabatrin for the fixed-ratio of 1:10 exerted supra-additive interaction (P<0.05), and simultaneously, the two-drug combinations for the fixed-ratios of 1:1, 1:2 and 1:5 produced additive interaction in the mouse 6Hz psychomotor seizure model. The combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10, as well as the combinations of levetiracetam with topiramate and vigabatrin for the fixed-ratio of 1:10 appear to be particularly favorable combinations exerting supra-additive interaction in the mouse 6Hz psychomotor seizure model. Finally, it may be concluded that because of the synergistic interactions between levetiracetam and carbamazepine, phenytoin, topiramate and vigabatrin, the combinations might be useful in clinical practice. PMID- 24211790 TI - Granulomatous slack skin with extracutaneous involvement and a good response to bortezomib-based chemotherapy. PMID- 24211789 TI - The first-night effect suppresses the strength of slow-wave activity originating in the visual areas during sleep. AB - Our visual system is plastic and adaptive in response to the stimuli and environments we experience. Although visual adaptation and plasticity have been extensively studied while participants are awake, little is known about what happens while they are asleep. It has been documented that sleep structure as measured by sleep stages using polysomnography is altered specifically in the first sleep session due to exposure to a new sleep environment, known as the first-night effect (FNE). However, the impact of the FNE on spontaneous oscillations in the visual system is poorly understood. How does the FNE affect the visual system during sleep? To address this question, the present study examined whether the FNE modifies the strength of slow-wave activity (SWA, 1-4Hz) the dominant spontaneous brain oscillation in slow-wave sleep-in the visual areas. We measured the strength of SWA originating in the visual areas during the first and the second sleep sessions. Magnetoencephalography, polysomnography, and magnetic resonance imaging were used to localize the source of SWA to the visual areas. The visual areas were objectively defined using retinotopic mapping and an automated anatomical parcellation technique. The results showed that the strength of SWA was reduced in the first sleep session in comparison to the second sleep session, especially during slow-wave sleep, in the ventral part of the visual areas. These results suggest that environmental novelty may affect the visual system through suppression of SWA. The impact of the FNE may not be negligible in vision research. PMID- 24211791 TI - Substance use and misuse in persons with intellectual disabilities (ID): results of a survey in ID and addiction services in Flanders. AB - Little is known about the characteristics of substance users with intellectual disabilities (ID). Nevertheless, this group is assumed to be at greater risk of developing substance misuse problems. This study focuses on substance users and misusers with ID, and investigates whether the two groups differ significantly in terms of the nature and consequences of their substance (mis)use. Information regarding the characteristics of the substance (mis)users, the substances used, the negative consequences of substance (mis)use, and the service use was collected through a questionnaire forwarded to ID and addiction services in Flanders. Caregivers identified 104 substance users and misusers with ID. Overall, few differences were observed between users and misusers. This finding underscores that substance use in persons with ID can have important consequences. Substance misusers, however, were found to have more mood changes, more suicidal ideation/thoughts, and more negative long-term consequences on their health, daily activity, and relationships due to substance misuse. Substance use and misuse were associated with mental health problems and were suggested to be a risk factor for offending behavior. To provide appropriate support for this specific population, an individualized approach is suggested that supports better intersectoral collaboration between services. PMID- 24211792 TI - Novel-word learning deficits in Mandarin-speaking preschool children with specific language impairments. AB - Children with SLI exhibit overall deficits in novel word learning compared to their age-matched peers. However, the manifestation of the word learning difficulty in SLI was not consistent across tasks and the factors affecting the learning performance were not yet determined. Our aim is to examine the extent of word learning difficulties in Mandarin-speaking preschool children with SLI, and to explore the potent influence of existing lexical knowledge on to the word learning process. Preschool children with SLI (n=37) and typical language development (n=33) were exposed to novel words for unfamiliar objects embedded in stories. Word learning tasks including the initial mapping and short-term repetitive learning were designed. Results revealed that Mandarin-speaking preschool children with SLI performed as well as their age-peers in the initial form-meaning mapping task. Their word learning difficulty was only evidently shown in the short-term repetitive learning task under a production demand, and their learning speed was slower than the control group. Children with SLI learned the novel words with a semantic head better in both the initial mapping and repetitive learning tasks. Moderate correlations between stand word learning performances and scores on standardized vocabulary were found after controlling for children's age and nonverbal IQ. The results suggested that the word learning difficulty in children with SLI occurred in the process of establishing a robust phonological representation at the beginning stage of word learning. Also, implicit compound knowledge is applied to aid word learning process for children with and without SLI. We also provide the empirical data to validate the relationship between preschool children's word learning performance and their existing receptive vocabulary ability. PMID- 24211793 TI - Characterization of cholinesterases in Chironomus riparius and the effects of three herbicides on chlorpyrifos toxicity. AB - In this study, the toxicities of four pesticides (the herbicides atrazine, terbuthylazine, metolachlor and the insecticide chlorpyrifos) previously detected in the Alqueva reservoir/dam (south of Portugal) were evaluated individually and in binary combinations of the herbicides and the insecticide using fourth-instar larvae of the aquatic midge Chironomus riparius. Chlorpyrifos induced toxicity to midges in all the 48 h toxicity bioassays performed. The swimming behaviour of the larvae was impaired, with EC50 values ranging from 0.15 to 0.17 MUg/L. However, neither s-triazine (atrazine and terbuthylazine) herbicides nor metolachlor alone at concentrations up to 200 MUg/L caused significant toxicity to C. riparius. When combined with both s-triazine herbicides, chlorpyrifos toxicity was enhanced by approximately 2-fold when tested in a binary mixture experimental setup, at the 50% effective concentration levels. To evaluate how chlorpyrifos toxicity was being increased, the cholinesterases (ChE) were characterized biochemically using different substrates and selective inhibitors. The results obtained suggested that the main enzyme present in this species is acetylcholinesterase (AChE) and therefore it was assayed upon C. riparius exposures to all pesticides individually and as binary mixtures. Although atrazine and terbuthylazine are not effective inhibitors of AChE, the potentiation of chlorpyrifos toxicity by the two s-triazine herbicides was associated with a potentiation in the inhibition of AChE in midges; both s triazine herbicides at 200 MUg/L increased the inhibition of the AChE activity by 7 and 8-fold, respectively. A strong correlation was observed between swimming behaviour disturbances of larvae and the inhibition of the AChE activity. In contrast, metolachlor did not affect chlorpyrifos toxicity at any of the concentrations tested. Therefore, the herbicides atrazine and terbuthylazine can act as synergists in the presence of chlorpyrifos, increasing the toxicity and consequently underestimating risk based on single chemical levels. PMID- 24211794 TI - Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria. AB - Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 MUM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6-7.8). Mitochondrial respiration was generally suppressed by 25 MUM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0-7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH was also protective against Cd in mitochondria of clams and oysters. In clams, 25 MUM Cd suppressed ADP-stimulated respiration at all pH; however, at low pH (6.6-7.0) this suppression was paralleled by a decrease in the rates of proton leak thereby effectively restoring mitochondrial coupling. In oysters, the inhibitory effects of Cd on ADP stimulated respiration were fully abolished at low pH (6.6-7.0). This indicates that moderate acidosis (such as occurs during exposure to air, extreme salinities or elevated CO2 levels in the intertidal zone) may have a beneficial side-effect of protecting mitochondria of clams and oysters against the toxic effects of trace metals in polluted estuaries. PMID- 24211795 TI - Changes in tolerance to herbicide toxicity throughout development stages of phototrophic biofilms. AB - Ecotoxicological experiments have been performed in laboratory-scale microcosms to investigate the sensitivity of phototrophic biofilm communities to the alachlor herbicide, in relation to the stages of phototrophic biofilm maturation (age of the phototrophic biofilms) and physical structure (intact biofilm versus recolonization). The phototrophic biofilms were initially cultivated on artificial supports in a prototype rotating annular bioreactor (RAB) with Taylor Couette type flow under constant operating conditions. Biofilms were collected after 1.6 and 4.4 weeks of culture providing biofilms with different maturation levels, and then exposed to nominal initial alachlor concentration of 10 MUg L( 1) in either intact or recolonized biofilms for 15 days in microcosms (mean time weighted average concentration - TWAC of 5.52 +/- 0.74 MUg L(-1)). At the end of the exposure period, alachlor effects were monitored by a combination of biomass descriptors (ash-free dry mass - AFDM, chlorophyll a), structural molecular fingerprinting (T-RFLP), carbon utilization spectra (Biolog) and diatom species composition. We found significant effects that in terms of AFDM, alachlor inhibited growth of the intact phototrophic biofilms. No effect of alachlor was observed on diatom composition or functional and structural properties of the bacterial community regardless of whether they were intact or recolonized. The intact three-dimensional structure of the biofilm did not appear to confer protection from the effects of alachlor. Bacterial community structure and biomass level of 4.4 weeks - intact phototrophic biofilms were significantly influenced by the biofilm maturation processes rather than alachlor exposure. The diatom communities which were largely composed of mobile and colonizer life-form populations were not affected by alachlor. This study showed that the effect of alachlor (at initial concentration of 10 MUg L(-1) or mean TWAC of 5.52 +/- 0.74 MUg L(-1)) is mainly limited to biomass reduction without apparent changes in the ecological succession trajectories of bacterial and diatom communities and suggested that carbon utilization spectra of the biofilm are not damaged resulting. These results confirmed the importance of considering the influence of maturation processes or community age when investigating herbicide effects. This is particularly important with regard to the use of phototrophic biofilms as bio indicators. PMID- 24211796 TI - The initial tolerance to sub-lethal Cd exposure is the same among ten naive pond populations of Daphnia magna, but their micro-evolutionary potential to develop resistance is very different. AB - Genetic variation complicates predictions of both the initial tolerance and the long-term (micro-evolutionary) response of natural Daphnia populations to chemical stressors from results of standard single-clone laboratory ecotoxicity tests. In order to investigate possible solutions to this problem, we aimed to compare the initial sub-lethal tolerance to Cd of 10 naive natural pond populations of Daphnia magna as well as their evolutionary potential to develop increased resistance. We did so by measuring reproductive performance of 120 clones, i.e. 12 clones hatched from the recent dormant egg bank of each of 10 populations, both in absence (Cd-free control) and presence of 4.4 MUg Cd/L. We show that the initial tolerance, defined as the reproductive performance of individuals of the first generation exposed to Cd relative to that in a Cd-free control was not significantly different among the 10 studied pond populations and averaged 0.82 +/- 0.04 over these populations. Moreover, these populations' initial tolerances were also not significantly different from the mean initial tolerance of 0.87 +/- 0.08 at 4.0 MUg Cd/L measured for a group of 7 often-used laboratory clones, collected from a range of European ecotoxicity testing laboratories. This indicates that the initial response of naive natural pond populations to sub-lethal Cd can be relatively accurately predicted from ecotoxicity test data from only a handful of laboratory clones. We then used estimates of broad-sense heritability of Cd tolerance (H(2)) - based on the same dataset - as a proxy of these populations' capacities to evolutionarily respond to Cd in terms of the development of increased resistance, which is here defined as the increase with time of the frequency of clones with a higher Cd tolerance in the population (accompanied with an increase of mean Cd-tolerance of the population above the initial tolerance). We show that the populations' estimated H(2) values of Cd-tolerance cover almost the entire theoretically possible range, ranging from not significantly different from zero (for five populations) to between 0.48 and 0.81 (for the five other populations). This indicates that, unlike the initial tolerance to Cd, the (long-term) micro-evolutionary response to Cd may be very different among natural pond populations. Therefore, we conclude that it may be very difficult to predict the long-term response of an unstudied population to chemical stress from tolerance data on a sample of other populations. It is therefore suggested that new methods for forecasting long-term responses should be explored, such as the development of predictive models based on the combination of population-genomic and tolerance time-series data. PMID- 24211798 TI - Sexually dimorphic long-term effects of an early life experience on AMPA receptor subunit expression in rat brain. AB - Neonatal handling, an experimental model of early life experiences, is known to affect hypothalamic-pituitary-adrenal (HPA) axis function, thus increasing adaptability, coping with stress, cognitive abilities and in general brain plasticity-related processes. AMPA receptors (AMPARs) mediate fast synaptic transmission at excitatory glutamatergic synapses in the CNS and are crucial during neuronal development, synaptic plasticity and structural remodeling. AMPARs are composed of four types of subunits, designated as AMPA glutamate receptor subunits (GluA1, GluA2, GluA3 and GluA4), which combine to form tetramers. The present study addressed the question of whether neonatal handling (15min daily maternal separation from postnatal day 1 (PND1) to PND21) might have an effect on GluA1-4 mRNA levels in adult rat male and female brain using in situ hybridization. We have identified selective sexually dimorphic effects of neonatal handling on the mRNA expression levels of AMPAR subunits in adult rat hippocampus and nuclei of the amygdaloid complex. In the dorsal hippocampus GluA1 mRNA levels were increased in handled males, while they were decreased in handled female animals. In the ventral hippocampus and the amygdaloid complex GluA2 mRNA was lower in handled females, while no effect was observed in handled males. Furthermore, we observed that neonatal handling induced in both sexes decreases of GluA2 mRNA in the dorsal hippocampus, as well as in the somatosensory and occipital cortex, of GluA3 mRNA in most hippocampal areas, amygdaloid complex and cortical regions studied, and of GluA4 mRNA in the ventral hippocampus. These results show that glutamatergic transmission is markedly affected by an early experience. The neonatal handling-induced alterations in AMPAR subunit composition are in line with the increased brain plasticity, the more effective HPA axis function, and in general the more adaptive behavioral phenotype known to characterize the handled animals. PMID- 24211799 TI - Three-dimensional structure of human lamellar bone: the presence of two different materials and new insights into the hierarchical organization. AB - Lamellar bone is the most common bone type in humans. The predominant components of individual lamellae are plywood-like arrays of mineralized collagen fibrils aligned in different directions. Using a dual-beam electron microscope and the Serial Surface View (SSV) method we previously identified a small, but significantly different layer in rat lamellar bone, namely a disordered layer with collagen fibrils showing little or no preferred orientation. Here we present a 3D structural analysis of 12 SSV volumes (25 complete lamellae) from femora of 3 differently aged human individuals. We identify the ordered and disordered motifs in human bone as in the rat, with several significant differences. The ordered motif shows two major preferred orientations, perpendicular to the long axis of the bone, and aligned within 10-20 degrees of the long axis, as well as fanning arrays. At a higher organizational level, arrays of ordered collagen fibrils are organized into 'rods' around 2 to 3MUm in diameter, and the long axes of these 'rods' are parallel to the lamellar boundaries. Human bone also contains a disordered component that envelopes the rods and fills in the spaces between them. The disordered motif is especially well-defined between adjacent layers of rods. The disordered motif and its interfibrillar substance stain heavily with osmium tetroxide and Alcian blue indicating the presence of another organic component in addition to collagen. The canalicular network is confined to the disordered material, along with voids and individual collagen fibrils, some of which are also aligned more or less perpendicular to the lamellar boundaries. The organization of the ordered fibril arrays into rods enveloped in the continuous disordered structure was not observed in rat lamellar bone. We thus conclude that human lamellar bone is comprised of two distinct materials, an ordered material and a disordered material, and contains an additional hierarchical level of organization composed of arrays of ordered collagen fibrils, referred to as rods. This new structural information on human lamellar bone will improve our understanding of structure-mechanical function relations, mechanisms of mechano sensing and the characterizations of bone pathologies. PMID- 24211797 TI - Neamine induces neuroprotection after acute ischemic stroke in type one diabetic rats. AB - INTRODUCTION: Angiogenin is a member of the ribonuclease superfamily and promotes degradation of the basement membrane and the extracellular matrix. After stroke in type one diabetes (T1DM) rats, Angiogenin is significantly increased and the Angiogenin is inversely correlated with functional outcome. Neamine, an aminoglycoside antibiotic, blocks nuclear translocation of Angiogenin, thereby abolishing the biological activity of Angiogenin. In this study, we therefore investigated the effect and underlying protective mechanisms of Neamine treatment of stroke in T1DM. METHODS: T1DM was induced in male Wistar rats by streptozotocin (60mg/kg, ip), and T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo). Neamine (10mg/kg ip) was administered at 2, 24 and 48h after the induction of embolic MCAo. A battery of functional outcome tests was performed. Blood-brain barrier (BBB) leakage, and lesion volume were evaluated and immunostaining, and Western blot were performed. RESULTS: Neamine treatment of stroke in T1DM rats significantly decreased BBB leakage and lesion volume as well as improved functional outcome compared to T1DM-control. Neamine also significantly decreased apoptosis and cleaved caspase-3 in the ischemic brain. Using immunostaining, we found that Neamine treatment significantly decreased nuclear Angiogenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB) activity, advanced glycation endproducts receptor (RAGE) number, the positive area of toll-like receptor 4 (TLR4) and increased Angeopoietin-1 expression compared to T1DM-MCAo control rats. Western blot results are consistent with the immunostaining. CONCLUSION: Neamine treatment of stroke is neuroprotective in T1DM rats. Inhibition of neuroinflammatory factor expression and decrease of BBB leakage may contribute to Neamine-induced neuroprotective effects after stroke in T1DM rats. PMID- 24211800 TI - Explore protein molecular structure in endosperm tissues in newly developed black and yellow type canola seeds by using synchrotron-based Fourier transform infrared microspectroscopy. AB - This study was conducted to characterize the protein molecular structure in endosperm tissues in newly developed black and yellow-type canola seeds by using synchrotron-based Fourier transform infrared microspectroscopy. The results showed that the yellow canola seeds contained relatively lower (P<0.05) percentage of beta-sheet and amide I and amide II area compared to the black-type canola seed. This might be an indication that the protein value of the yellow canola seeds as food or feed is different from that of the black canola seeds. The multivariate molecular spectral analyses (AHCA, PCA) showed that there were not significant molecular structural differences in the protein amide I and amide II fingerprint region (ca. 1720-1480 cm(-1)) between the yellow and the black type of canola seed. It can be concluded that both the yellow and the black seeded canola contain the same proteins but in different ratios. PMID- 24211801 TI - Bis-amide transition metal complexes: isomerism and DNA interaction study. AB - A quatridentate bis-amide ligand, N,N'-propylenebis(salicylamide) H2pbs, and its transition metal complexes [M(pbs)(H2O)2], where M=Co(II), Ni(II), Cu(II), and Zn(II) have been synthesized and characterized by elemental analysis, UV-Vis, IR, NMR, Mass, EPR, molar conductivity, magnetic moment values and thermal analysis. The NMR spectrum of ligand evidences the E/Z isomerism. All the evidences reveal that the metal ions adopt octahedral geometry with metal:ligand:solvent ratio 1:1:2. The conductivity measurements exhibit that the complexes are non electrolytes. DNA binding properties of these complexes have been explored by UV Vis and cyclic voltammetry. The results indicate that these complexes are good intercalators. PMID- 24211802 TI - Development of portable mass spectrometer with electron cyclotron resonance ion source for detection of chemical warfare agents in air. AB - A portable mass spectrometer with an electron cyclotron resonance ion source (miniECRIS-MS) was developed. It was used for in situ monitoring of trace amounts of chemical warfare agents (CWAs) in atmospheric air. Instrumental construction and parameters were optimized to realize a fast response, high sensitivity, and a small body size. Three types of CWAs, i.e., phosgene, mustard gas, and hydrogen cyanide were examined to check if the mass spectrometer was able to detect characteristic elements and atomic groups. From the results, it was found that CWAs were effectively ionized in the miniECRIS-MS, and their specific signals could be discerned over the background signals of air. In phosgene, the signals of the 35Cl+ and 37Cl+ ions were clearly observed with high dose-response relationships in the parts-per-billion level, which could lead to the quantitative on-site analysis of CWAs. A parts-per-million level of mustard gas, which was far lower than its lethal dosage (LCt50), was successfully detected with a high signal-stability of the plasma ion source. It was also found that the chemical forms of CWAs ionized in the plasma, i.e., monoatomic ions, fragment ions, and molecular ions, could be detected, thereby enabling the effective identification of the target CWAs. Despite the disadvantages associated with miniaturization, the overall performance (sensitivity and response time) of the miniECRIS-MS in detecting CWAs exceeded those of sector-type ECRIS-MS, showing its potential for on-site detection in the future. PMID- 24211803 TI - Vibrational spectroscopic (FT-IR, FT-Raman) and quantum chemical calculations of 1-(5,5-dioxido-10H-phenothiazin-10-yl)ethanone. AB - FT-IR and FT-Raman spectra of 1-(5,5-dioxido-10H-phenothiazin-10-yl)ethanone were recorded and analyzed. The vibrational wavenumbers were computed using B3LYP/6 31G* and SDD basis. Potential energy distribution of normal modes of vibrations was done using GAR2PED program. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper conjugative interaction and charge delocalization has been analyzed using NBO analysis. Molecular electrostatic potential was performed by the DFT method and infrared intensities and Raman activities are also reported. MEP shows that the negative potential sites are on oxygen atoms and the positive potential sites are around the nitrogen atoms. The geometrical parameters of the title compound (SDD) are in agreement with XRD crystal structure data. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive object for future studies of nonlinear optics. PMID- 24211804 TI - Investigation on the interactions of clenbuterol to bovine serum albumin and lysozyme by molecular fluorescence technique. AB - Clenbuterol interacting with bovine serum albumin (BSA) or lysozyme (LYS) in physiological buffer (pH 7.4) was investigated by the fluorescence spectroscopy and UV-vis absorption spectroscopy. The results indicated that clenbuterol quenched the intrinsic fluorescence of BSA and LYS via a static quenching procedure. The binding constants of clenbuterol with BSA and LYS were 1.16*10(3) and 1.49*10(3) L mol(-1) at 291 K. The values of DeltaH and DeltaS implied that hydrophobic and electrostatic interaction played a major role in stabilizing the complex (clenbuterol-BSA or clenbuterol-LYS). In the presence of Fe2+, Fe3+, Cu2+, Mg2+, Ca2+, or Zn2+, the binding constants of clenbuterol to BSA or LYS had no significant differences. The distances between the donor (BSA or LYS) and acceptor (clenbuterol) were 2.61 and 2.19 nm for clenbuterol-BSA and clenbuterol LYS respectively. Furthermore, synchronous fluorescence spectrometry was used to analyze the conformational changes of BSA and LYS. PMID- 24211805 TI - Anti-proliferative effect of a compound isolated from Cassia auriculata against human colon cancer cell line HCT 15. AB - The compound was isolated from leaves of Cassia auriculata and its structure was characterized using high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology and lactate dehydrogenase assay of isolated compound was tested against human colon cancer cell line HCT 15. The isolated compound, 4-(4-chlorobenzyl)-2,3,4,5,6,7-hexahydro-7-(2 ethoxyphenyl)benzo[h][1,4,7]triazecin-8(1H)-one at 25MUg/ml concentration and by 48h showed 50% inhibition of human colon cancer cells (HCT 15). The results suggest that isolated compound from C. auriculata has potential to prevent colon cancer cell line. PMID- 24211806 TI - Studies of interaction between terbium(III)-deferasirox and double helix DNA by spectral and electrochemical methods. AB - DNA binding studies of terbium(III)-deferasirox (Tb3+-DFX) complex were monitored to understand the reaction mechanism and introduce a new probe for the assay of DNA. In the present work, UV absorption spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), cyclic voltammetry (CV) and viscosity measurement were employed to study the interactions of Tb3+-DFX with calf thymus DNA (ctDNA). The binding of Tb3+-DFX complex to ctDNA showed a hyperchromic effect in the absorption spectra and the increase in fluorescence quenching effect (amount) of Tb3+-DFX complex in the presence of ctDNA. The binding constants (Kb) for the complex with ctDNA were estimated to be 1.8*10(4) M(-1) through UV absorption spectrophotometry and fluorescence spectroscopy. Upon addition of the complex, clear decreases were observed in the viscosity of ctDNA. The CD spectra indicated that there are certain detectable conformational changes in the DNA double helix when the complex was added. The CV method showed that both anodic and cathodic peak potentials of Tb3+-DFX complex showed negative shifts on the addition of the ctDNA. Further, competitive methylene blue binding studies with fluorescence spectroscopy have shown that the complex can bind to ctDNA through nonintercalative mode. The experimental results suggest that Tb3+ DFX complex binds to DNA via groove binding and/or electrostatic binding mode. PMID- 24211807 TI - Exploring the structure-activity relations of N-carbethoxyphthalimide by combining FTIR, FT-Raman and NMR spectroscopy with DFT electronic structure method. AB - The complete vibrational assignment and analysis of N-carbethoxyphthalimide were carried out using the experimental FTIR and FT-Raman data in the range 4000-450 and 4000-100 cm(-1), respectively along with quantum chemical studies of the compound using DFT-B3LYP gradient calculations employing the 6-31G**, 6-311++G** and cc-pVDZ basis sets. The 1H (400 MHz; CDCl3) and 13C (100 MHz;CDCl3) nuclear magnetic resonance (NMR) spectra were also recorded. Due to the partial ionic nature of the carbonyl group, the carbon atoms C1 and C3 in NCEP show downfield effect and the corresponding observed chemical shift of both are observed at 163.76 ppm and the carbon atom C16 in the carbethoxy group also give signal in the downfield at 148.45 ppm. The active sites are determined by molecular electrostatic potential. The possible electronic transitions are determined by HOMO and LUMO orbital shapes and their energies. The structure-chemical reactivity relations of the compound were determined through chemical potential, global hardness, global softness, electronegativity, electrophilicity and local reactivity descriptors by conceptual DFT methods. PMID- 24211808 TI - Synthesis, spectral, and anti-microbial studies of thioiminium iodides and amine hydrochlorides. AB - To avoid the undesired deprotonation during the addition of organolithium and organomagnesium reagents to ketones, the thioiminium salts, easily prepared from lactams and amides are converted into 2,2-disubstituted and 2-monosubstituted amines by reaction with simple nucleophiles such as organocerium and organocopper reagents. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated. These thioiminium iodides act as good electrophiles and accept alkylceriums towards bisaddition. The newly synthesized amines have been characterized by 1H and 13C NMR, IR and mass spectra. The amines have been converted into their hydrochlorides and characterized by COSY. These hydrochlorides have been subjected to antimicrobial screening with clinically isolated microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans. The hydrochlorides show quite good activity against these bacteria and fungus. PMID- 24211809 TI - Spectral kinetics of fluorescence spectra of fluoroderivatives of pyrazoloquinoline in different polymer matrices. AB - Three fluoro-substituted pyrazoloquinoline derivatives have been placed in polymer matrices: polycarbonate, poly(methyl methacrylate) and polystyrene. Absorption, excitation and time-resolved fluorescence spectra have been recorded and luminescence lifetime of the optically active composites has been determined. Influence of the dielectric environment the optical properties of the chromophores are discussed. Experimental data and conclusions are supported with (TD)DFT calculations. PMID- 24211810 TI - Fast determination of two atractylenolides in Rhizoma Atractylodis Macrocephalae by Fourier transform near-infrared spectroscopy with partial least squares. AB - Rhizoma Atractylodis Macrocephalae (RAM) is a commonly used food and traditional Chinese medicine (TCM), which traditionally strengthens the spleen, benefits vital energy, eliminates dampness, and promotes hidroschesis. Its primary effective constituents are polysaccharides and volatile oil, whose main components are atractylenolide I and III. Fourier transform near-infrared spectroscopy (FT-NIR) is widely used in TCM research. However, determination of atractylenolides in RAM using FT-NIR has not been described. In this study, a new method for the determination of atractylenolides I and III in RAM by NIR was established. The spectral characteristics of atractylenolides I and III were obtained by second derivative multiple scattering correction, and its chart to the original absorbance spectra. Additionally, in combination with the partial least squares (PLS) algorithm, the calibration process was performed for the quantitation of the samples. The root mean square error of cross-validation of the PLS models for atractylenolides I and III was 0.0387 and 0.0358, and the determination coefficient of quantitative models was 96.63 and 96.16, respectively. This study demonstrated that NIR spectroscopy can be used to analyze quickly and efficiently the contents of atractylenolides I and III in RAM. PMID- 24211811 TI - Spectroscopic studies on gallic acid and its azo derivatives and their iron(III) complexes. AB - Azo gallic derivatives and their iron(III) complexes were synthesized and characterized. The stereochemistry and the mode of bonding of the complexes were achieved based on elemental analysis, UV-Vis and IR. The thermal behaviors of the complexes were studied. The effect of pH on the electronic absorption spectra of gallic acid and its azo derivatives are discussed. Different spectroscopic methods (molar ratio, straight line method, continuous variation, slope ratio and successive method) are applied for determination of stoichiometry and pK values for the complex formation of gallic acid with iron(III) in aqueous media. Iron(III) complexes of gallic acid is formed with different ratio: 1:1, 1:2, 1:3 and 1:4 (M:L). PMID- 24211812 TI - Investigation on the interaction between endocrine disruptor triphenyltin with human serum albumin. AB - The interaction between triphenyltin (TPT) and human serum albumin (HSA) in physiological buffer (pH=7.4) was investigated by the fluorescence quenching technique. The results of fluorescence titration revealed that TPT could strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. The apparent binding constants K and number of binding sites n of TPT with HSA were 2.51*10(3) and 0.96 at 298 K which were obtained by the fluorescence quenching method. The thermodynamic parameters enthalpy change (DeltaH), entropy change (DeltaS) were positive, which indicated that the interaction of TPT with HSA was driven mainly by hydrophobic forces. The process of binding was a spontaneous process in which Gibbs free energy change was negative. The distance r between donor (HSA) and acceptor (TPT) was calculated to be 3.13 nm based on Forster's non-radiative energy transfer theory. The results of synchronous fluorescence, three-dimensional fluorescence and circular dichroism (CD) spectra showed that the triphenyltin induced conformational changes of HSA. PMID- 24211813 TI - Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis. AB - Patients with idiopathic pulmonary fibrosis (IPF) have significantly impaired pulmonary diffusion, which may affect the pulmonary concentration of many drugs, including antibiotics. In this study, we compared the difference in pulmonary levofloxacin (LVFX) concentration between patients with normal lung function and IPF. The IPF group included 10 patients with a proven diagnosis of IPF and a diffusing capacity for carbon monoxide ranging from 40% to 70% of predicted values. The control group included 10 patients with normal pulmonary function. Blood and bronchoalveolar lavage fluid (BALF) were taken at 3-3.5 h after fasting. LVFX (500 mg) was administered orally. LVFX concentrations in the serum and BALF were determined using HPLC-MS/MC. The level of LVFX in alveolar epithelial lining fluid (ELF) was calculated using the following formula: LVFX ELF = LVFX BALF * (Urea serum/Urea BALF). No significant differences in age, body weight, height, and calculated creatinine clearance and BALF retrieval rate were observed between groups. LVFX serum concentrations in the IPF and control groups were (5.97 +/- 1.28) MUg/ml and (6.84 +/- 3.43) MUg/ml, respectively (P = 0.4727). ELF concentration of LVFX in the control group was (27.81 +/- 21.36) MUg/ml, while the concentration in the IPF group was (10.17 +/- 2.46) MUg/ml, less than half of that in the controls (P = 0.0058). The intrapulmonary concentration of LVFX in IPF patients was lower than those with normal lung function. Notably, however, the ELF LVFX concentration following 500 mg once daily exceeded the MIC90 of common respiratory pathogens. Excellent antibacterial efficacy of LVFX can be expected for IPF patients in the treatment of respiratory tract infections. PMID- 24211815 TI - Food safety knowledge, practices and beliefs of primary food preparers in families with young children. A mixed methods study. AB - Food preparers in families with young children are responsible for safe food preparation and handling to prevent foodborne illness. To explore the food safety perceptions, beliefs, and practices of primary food preparers in families with children 10 years of age and younger, a mixed methods convergent parallel design and constructs of the Health Belief Model were used. A random sampling of 72 primary food handlers (36.2+/-8.6 years of age, 88% female) within young families in urban and rural areas of two Midwestern states completed a knowledge survey and participated in ten focus groups. Quantitative data were analyzed using SPSS. Transcribed interviews were analyzed for codes and common themes. Forty-four percent scored less than the average knowledge score of 73%. Participants believe children are susceptible to foodborne illness but perceive its severity to be low with gastrointestinal discomfort as the primary outcome. Using safe food handling practices and avoiding inconveniences were benefits of preventing foodborne illness. Childcare duties, time and knowledge were barriers to practicing food safety. Confidence in preventing foodborne illness was high, especially when personal control over food handling is present. The low knowledge scores and reported practices revealed a false sense of confidence despite parental concern to protect their child from harm. Food safety messages that emphasize the susceptibility and severity of foodborne illness in children are needed to reach this audience for adoption of safe food handling practices. PMID- 24211814 TI - Improved segmentation of white matter tracts with adaptive Riemannian metrics. AB - We present a novel geodesic approach to segmentation of white matter tracts from diffusion tensor imaging (DTI). Compared to deterministic and stochastic tractography, geodesic approaches treat the geometry of the brain white matter as a manifold, often using the inverse tensor field as a Riemannian metric. The white matter pathways are then inferred from the resulting geodesics, which have the desirable property that they tend to follow the main eigenvectors of the tensors, yet still have the flexibility to deviate from these directions when it results in lower costs. While this makes such methods more robust to noise, the choice of Riemannian metric in these methods is ad hoc. A serious drawback of current geodesic methods is that geodesics tend to deviate from the major eigenvectors in high-curvature areas in order to achieve the shortest path. In this paper we propose a method for learning an adaptive Riemannian metric from the DTI data, where the resulting geodesics more closely follow the principal eigenvector of the diffusion tensors even in high-curvature regions. We also develop a way to automatically segment the white matter tracts based on the computed geodesics. We show the robustness of our method on simulated data with different noise levels. We also compare our method with tractography methods and geodesic approaches using other Riemannian metrics and demonstrate that the proposed method results in improved geodesics and segmentations using both synthetic and real DTI data. PMID- 24211816 TI - At the frontier of progress for paediatric oncology: the neuroblastoma paradigm. AB - INTRODUCTION: Neuroblastoma is one of the commonest and deadliest forms of childhood cancer and major initiatives are ongoing to improve the outcome of these patients. SOURCES OF DATA: Data for this review were obtained from PubMed and abstracts from the American Society of Clinical Oncology and Advances in Neuroblastoma Research. AREAS OF AGREEMENT: Collaborative clinical trials have led to major improvements in treatment outcomes for low and intermediate risk neuroblastoma, and international initiatives such as the International Neuroblastoma Risk Group have produced a very refined risk stratification incorporating clinical and biological risk factors. AREAS OF CONTROVERSY: Despite many efforts, the outcome for high-risk neuroblastoma is still poor and the only new strategy incorporated into frontline treatment is anti-GD2 immunotherapy. It is unclear how new drugs targeting specific molecular aberrations will be incorporated. GROWING POINTS: Genomic characterization and drug development have undergone major advances in the last 5 years leading to a much deeper understanding of tumour biology as well as active biomarker-driven preclinical and clinical research on new molecules that will hopefully progress faster and more efficiently into frontline combination treatment strategies. AREAS TIMELY FOR DEVELOPING RESEARCH: Significant effort remains to be done in integrating the different new strategies, combining new molecularly targeted agents to maximize therapeutic benefit and incorporate immunotherapy together with targeted therapies. PMID- 24211817 TI - Targeted reinforcement of neural oscillatory activity with real-time neuroimaging feedback. AB - Biofeedback and brain-computer interfacing using EEG has been receiving continuous and increasing interest. However, the limited spatial resolution of low-density scalp recordings is a roadblock to the unequivocal monitoring and targeting of neuroanatomical regions and physiological signaling. This latter aspect is pivotal to the actual efficiency of neurofeedback procedures, which are expected to engage the modulation of well-identified components of neural activity within and between predetermined brain regions. Our group has previously contributed to demonstrate the principles of real-time magnetoencephalography (MEG) source imaging. Here we show how the technique was further developed to provide healthy subjects with region-specific neurofeedback to modulate successfully predetermined components of their brain activity in targeted brain regions. Overall, our results positively indicate that neurofeedback based on time-resolved MEG imaging has the potential to become an innovative therapeutic approach in neurology and neuropsychiatry. PMID- 24211818 TI - Early anti-correlated BOLD signal changes of physiologic origin. AB - Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (CDB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative CDB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin. PMID- 24211819 TI - The Efficacy of InSight Cognitive Training to Improve Useful Field of View Performance: A Brief Report. AB - OBJECTIVE: It is well established that cognitive speed of processing training (SOPT) improves Useful Field of View (UFOV) performance and transfers to enhanced performance of instrumental activities of daily living, including driving. InSight is a recently developed version of SOPT formatted for self-administration by older adults with exercises translated into a gaming format. The goal was to examine whether InSight training improves UFOV performance. METHOD: Participants ranged in age between 59-95 years and were randomized to InSight cognitive training or a control condition. Cognitive performance and self-perceptions were measured pre- and post-training, or for controls, after an equivalent delay. Participants completed training twice a week over a 12-week period with the goal of completing 20 sessions. RESULTS: Participants randomized to InSight training experienced greater improvements in their UFOV performance relative to the control condition, F(1, 58) = 4.26, p = .043, but no changes in cognitive self perceptions were found. CONCLUSIONS: The InSight program is a viable tool for enhancing older adults' UFOV performance. Future research should examine if training gains from the program endure and transfer to improved everyday function. PMID- 24211820 TI - Hybrid fluorescence and electron cryo-microscopy for simultaneous electron and photon imaging. AB - Integration of fluorescence light and transmission electron microscopy into the same device would represent an important advance in correlative microscopy, which traditionally involves two separate microscopes for imaging. To achieve such integration, the primary technical challenge that must be solved regards how to arrange two objective lenses used for light and electron microscopy in such a manner that they can properly focus on a single specimen. To address this issue, both lateral displacement of the specimen between two lenses and specimen rotation have been proposed. Such movement of the specimen allows sequential collection of two kinds of microscopic images of a single target, but prevents simultaneous imaging. This shortcoming has been made up by using a simple optical device, a reflection mirror. Here, we present an approach toward the versatile integration of fluorescence and electron microscopy for simultaneous imaging. The potential of simultaneous hybrid microscopy was demonstrated by fluorescence and electron sequential imaging of a fluorescent protein expressed in cells and cathodoluminescence imaging of fluorescent beads. PMID- 24211821 TI - NMR structural studies of the first catalytic half-domain of ubiquitin activating enzyme. AB - We report a high resolution NMR structure and (15)N relaxation studies of the first catalytic cysteine half-domain (FCCH) of the mouse ubiquitin-activating enzyme E1, together with interaction studies of FCCH and the other catalytic E1 subdomain - SCCH (second catalytic cysteine half-domain). In solution, mouse FCCH forms a well-defined six-stranded antiparallel beta-barrel structure, a common fold for many proteins with a variety of cellular functions. (15)N relaxation data reveal FCCH complex backbone dynamics and indicate which residues experience slow intramolecular motions. Some of these residues make contacts with the polar face of ubiquitin in the co-crystal structure of yeast E1 and ubiquitin. However, the titration of FCCH with ubiquitin does not show any visible chemical shift changes in the 2D (1)H/(15)N HSQC spectra of the FCCH. The 2D (1)H/(15)N HSQC experiments performed both for each catalytic half-domain individually and for their equimolar mixture in the milimolar concentration range display no detectable chemical shift perturbation, suggesting a lack of interaction between the two subdomains unless they are covalently linked via the adenylation domain. PMID- 24211822 TI - Practical workflow for cryo focused-ion-beam milling of tissues and cells for cryo-TEM tomography. AB - Vitreous freezing offers a way to study cells and tissue in a near-native state by cryo-transmission electron microscopy (cryo-TEM), which is important when structural information at the macromolecular level is required. Many cells - especially those in tissue - are too thick to study intact in the cryo-TEM. Cryo focused-ion-beam (cryo-FIB) milling is being used in a few laboratories to thin vitreously frozen specimens, thus avoiding the artifacts and difficulties of cryo ultramicrotomy. However, the technique is challenging because of the need to avoid devitrification and frost accumulation during the entire process, from the initial step of freezing to the final step of loading the specimen into the cryo TEM. We present a robust workflow that makes use of custom fixtures and devices that can be used for high-pressure-frozen bulk tissue samples as well as for samples frozen on TEM grids. PMID- 24211823 TI - Outcomes in catheter ablation of ventricular tachycardia in dilated nonischemic cardiomyopathy compared with ischemic cardiomyopathy: results from the Prospective Heart Centre of Leipzig VT (HELP-VT) Study. AB - BACKGROUND: Data on the outcomes of ventricular tachycardia (VT) ablation in nonischemic dilated cardiomyopathy (NIDCM) are insufficient. The Heart Center of Leipzig VT (HELP-VT) study was conducted prospectively to compare outcomes after radiofrequency catheter ablation of VT in patients with NIDCM compared with ischemic cardiomyopathy (ICM). METHODS AND RESULTS: Two hundred twenty-seven patients, 63 with NIDCM and 164 with ICM, presenting with sustained VT were ablated with radiofrequency catheter ablation. Noninducibility of any clinical and nonclinical VT was achieved in 66.7% of NIDCM and in 77.4% of ICM patients. Ablation of the clinical VT only was achieved in 18.3% of ICM and in 22.2% of NIDCM patients. There was no statistically significant difference in short-term outcomes between the 2 groups. At the 1-year follow-up, VT-free survival in NIDCM was 40.5% compared with 57% in ICM. In univariate analysis, the hazard ratio for VT recurrence was significantly higher for NIDCM (1.62; 95% confidence interval, 1.12- 2.34; P=0.01). In both the ICM and NIDCM subgroups, procedure failure and incomplete procedural success were independent predictors of VT recurrence. CONCLUSIONS: Although the short-term success rates after VT ablation in NIDCM and ICM patients were similar, the long-term outcomes in NIDCM patients were significantly worse. Complete VT noninducibility at the end of the ablation is associated with beneficial long-term outcome in NIDCM. Pursuing compete elimination of all inducible VTs is desirable and may improve the long-term success in NIDCM. PMID- 24211824 TI - Role of hemostatic factors on the risk of venous thrombosis in people with impaired kidney function. AB - BACKGROUND: Factors explaining the association between impaired kidney function and venous thrombosis have not been identified so far. The aim of our study was to determine whether the association between impaired kidney function and venous thrombosis can be explained by the concurrent presence of genetic or acquired venous thrombosis risk factors. METHODS AND RESULTS: The glomerular filtration rate was estimated (eGFR) in 2473 venous thrombosis patients and 2936 controls from a population-based case-control study. Kidney function was grouped into 6 categories based on percentiles of the eGFR in the controls (>50th [reference], 10th-50th, 5th-10th, 2.5th-5th, 1st-2.5th, and <1st percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor. Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) and von Willebrand factor levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) increased with each percentile category. The odds ratios for venous thrombosis similarly increased across the categories from 1.1 (95% confidence interval, 0.9-1.3) for the 10th to 50th percentile to 3.7 (95% confidence interval, 2.4-5.7) for the <1st percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these odds ratios, indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the odds ratios. CONCLUSION: Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels. PMID- 24211825 TI - Acquired bilateral nevoid telangiectasia: report of 9 cases. PMID- 24211826 TI - Reconstruction of the natural history of metastatic cancer and assessment of the effects of surgery: Gompertzian growth of the primary tumor. AB - This work deals with retrospective reconstruction of the individual natural history of solid cancer and assessment of the effects of treatment on metastatic progression. This is achieved through a mathematical model of cancer progression accounting for the growth of the primary tumor, shedding of metastases, their dormancy and growth at secondary sites. To describe dynamics of the primary tumor, we used the Gompertz law, a parsimonious model of tumor growth accounting for its saturation. Parameters of the model were estimated from the age and volume of the primary tumor at surgery and volumes of detectable bone metastases collected from one breast cancer patient and one prostate cancer patient. This allowed us to estimate, for each patient, the ages at cancer onset and inception of all detected metastases, the expected metastasis latency time, parameters of the Gompertzian growth of the primary tumor, and the rates of growth of metastases before and after surgery. We found that for both patients: (1) onset of metastasis occurred when primary tumor was undetectable; (2) inception of all surveyed metastases except one occurred before surgery; and most importantly, (3) resection of the primary tumor led to a dramatic increase in the rate of growth of metastases. The model provides an excellent fit to the observed volumes of bone metastases in both patients. Our results agree well with those obtained previously based on exponential growth of the primary tumor, which serves as model validation. Our findings support the notion of metastatic dormancy and indirectly confirm the existence of stem-like cancer cells in breast and prostate tumors. We also explored the logistic law of primary tumor growth; however, it degenerated into the exponential law for both patients analyzed. The conclusions of this work are supported by a vast body of experimental, clinical and epidemiological knowledge accumulated over the last century. PMID- 24211827 TI - Chitosan-ionic liquid modified single-use sensor for electrochemical monitoring of sequence-selective DNA hybridization. AB - Chitosan-(CHIT) and ionic liquid- (1-butyl-3-methylimidazolium hexafluorophosphate (IL)) modified single-use graphite electrodes (PGEs) were developed for the first time in the present study for the enhanced monitoring of DNA, and also for sequence-selective DNA hybridization by measuring the guanine oxidation signal. The electrochemical behaviour of the CHIT-IL modified electrodes was first investigated (with unmodified electrodes as controls) using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Sequence-selective DNA hybridization related to Hepatitis B virus (HBV) was also evaluated in the case of hybridization between amino-linked HBV probe and its complementary (target), a noncomplementary (NC) sequence, single base mismatch (MM), and also in the medium of target/mismatch (MM) mixtures (1:1). CHIT-IL modified PGEs presented a very effective discrimination of DNA hybridization owing to their superior selectivity and sensitivity. PMID- 24211828 TI - Biosynthesis of lead nanoparticles by the aquatic water fern, Salvinia minima Baker, when exposed to high lead concentration. AB - Salvinia minima Baker is a small floating aquatic fern that is efficient for the removal and storage of heavy metals such as lead and cadmium. In this study, we report that lead removal by S. minima causes large accumulation of lead inside the cells in the form of nanoparticles (PbNPs). The accumulation pattern of lead was analyzed in both, submerged root-like modified fronds (here named "roots"), and in its aerial leaf-like fronds ("leaves"). Analysis by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRTEM) confirmed the biosynthesis of PbNPs by the plant. In both, roots and leaves, PbNPs were found to accumulate almost exclusively at the cell wall and closely associated to the cell membrane. Two types of PbNPs shapes were found in cells of both tissues, those associated to the cell wall were quasi-spherical with 17.2+/-4.2 nm of diameter, while those associated to the cell membrane/cytoplasm were elongated. Elongated particles were 53.7+/-29.6 nm in length and 11.1+/-2.4 nm wide. Infrared spectroscopy (IR) results indicate that cellulose, lignin and pectin are the major components that may be acting as the reducing agents for lead ions; these findings strongly suggest the potential use of this fern to further explore the bio-assisted synthesis of heavy metal nanostructures. PMID- 24211830 TI - Role of hypothalamic corticotropin-releasing factor in mediating alcohol-induced activation of the rat hypothalamic-pituitary-adrenal axis. AB - Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis through brain based mechanisms in which endogenous corticotropin-releasing factor (CRF) plays a major role. This review first discusses the evidence for this role, as well as the possible importance of intermediates such as vasopressin, nitric oxide and catecholamines. We then illustrate the long-term influence exerted by alcohol on the HPA axis, such as the ability of a first exposure to this drug during adolescence, to permanently blunt neuroendocrine responses to subsequent exposure of the drug. In view of the role played by CRF in addiction, it is likely that a better understanding of the mechanisms through which this drug stimulates the HPA axis may lead to the development of new therapies used in the treatment of alcohol abuse, including clinically relevant CRF antagonists. PMID- 24211829 TI - Interferon alpha induced intrahepatic pSTAT1 inversely correlate with serum HCV RNA levels in chronic HCV infection. AB - BACKGROUND: The Jak-STAT signaling of hepatitis C virus (HCV) infected hepatocyte is critical for the antiviral action of endogenously produced interferon (IFN) as well as exogenously administered interferon alpha (IFN-alpha). The activation of cellular Jak-STAT signaling by IFN-alpha results in the phosphorylation and nuclear translocation of pSTAT1 and pSTAT2 proteins to induce antiviral gene transcription. Clinical studies show that chronic HCV patients with high viral load show poor response to interferon alpha and ribavirin combination therapy. AIM: We seek to determine whether the IFN-alpha induced activation of pSTAT1 and pSTAT2 in hepatocytes isolated from liver biopsy of patients chronically infected with hepatitis C virus could be related to the viral load. METHOD: Hepatocytes were isolated from liver biopsies of 18 chronic HCV patients using the collagen digestion method. Induction of pSTAT1 protein in the isolated hepatocyte was measured after IFN-alpha treatment. The fold change in the levels of pStat1 in the cell lysates due to IFN-treatment was measured by Western blot analysis followed by densitometry analysis. RESULTS: Results of our study indicate that IFN-alpha induced pSTAT1 levels vary in chronically infected hepatocytes from chronic HCV patients. Semi-quantitative analysis of the pSTAT1 bands revealed a median induction of 7.4-fold in non-infected primary hepatocytes and 2.3-fold in chronic hepatitis C patients (p < 0.001). Total STAT1 levels were not significantly different between treated and untreated primary hepatocytes. We also found a significantly inverse correlation between the intrahepatic pSTAT1 inductions with the serum HCV RNA levels. CONCLUSION: We have developed an antibody based Western blot detection method to measure intrahepatic pStat1 and pStat2 levels to assess the cellular response to exogenous IFN-alpha. Our results indicate that pStat1 activation is a good indicator to assess the level of HCV replication in chronic HCV patients. PMID- 24211831 TI - Regulation of galectin-3-induced apoptosis of Jurkat cells by both O-glycans and N-glycans on CD45. AB - Galectin-3 has been reported to induce apoptosis of Jurkat cells through binding receptors such as CD45. CD45RABC is heavily O-glycosylated and N-glycosylated, while CD45RO is only N-glycosylated. In this study, no apoptosis induced by galectin-3 was detected in CD45RO-transfected cells, whereas apoptosis of CD45RABC-transfected cells was observed, implying that O-glycans on CD45 might play roles in galectin-3-induced apoptosis. O-Glycosylation inhibition assay further suggests the role of O-glycans on CD45 in regulation of galectin-3 induced apoptosis. We also found that deglycosylation at N327 of CD45RO resulted in increased binding to galectin-3 without affecting apoptosis, while deglycosylation at N36 or N109 of CD45RO enhanced galectin-3-induced apoptosis. These data demonstrate that galectin-3-induced apoptosis of Jurkat cells is regulated by both O-glycans and N-glycans on CD45. PMID- 24211832 TI - Mutations of Asp540 and the domain-connecting residues synergistically enhance Pyrococcus furiosus DNA ligase activity. AB - The structure of Pyrococcus furiosus DNA ligase (PfuLig), which architecturally resembles human DNA ligase I (hLigI), revealed that the C-terminal helix stabilizes the closed conformation through several ionic interactions between two domains (adenylylation domain (AdD) and C-terminal OB-fold domain (OBD)). This helix is oriented differently in DNA-bound hLigI, suggesting that the disruption of its interactions with AdD facilitates DNA binding. Previously, we demonstrated that the replacement of Asp540 with arginine improves the ligation activity. Here we report that the combination of the Asp540-replacement and the elimination of ionic residues in the helix, forming interactions with AdD, effectively enhanced the activity. PMID- 24211833 TI - Solution NMR studies of the plant peptide hormone CEP inform function. AB - The C-terminally Encoded Peptide (CEP) family of regulatory peptides controls root development in vascular plants. Here, we present the first NMR structures of CEP. We show that root-knot nematode (RKN: Meloidogyne spp.) also encodes CEP, presumably to mimic plant CEP as part of their stereotypic, parasitic interaction with vascular plants. Molecular dynamics simulations of plant- and nematode encoded CEP displaying known posttranslational modifications (PTM) provided insight into the structural effects of PTM and the conformational plasticity and rigidity of CEP. Potential mechanisms of action are discussed with respect to the structure and sampling of conformational space. PMID- 24211834 TI - BAP1 is phosphorylated at serine 592 in S-phase following DNA damage. AB - The human BAP1 deubiquitinating enzyme is a chromatin-bound transcriptional regulator and tumor suppressor. BAP1 functions in suppressing cell proliferation, yet its role in the DNA damage response pathway is less understood. In this study we characterized DNA damage-induced phosphorylation of BAP1 at serine 592 (pS592) and the cellular outcomes of this modification. In contrast to the majority of BAP1, pS592-BAP1 is predominantly dissociated from chromatin. Our findings support a model whereby stress induced phosphorylation functions to displace BAP1 from specific promoters. We hypothesize that this regulates the transcription of a subset of genes involved in the response to DNA damage. PMID- 24211835 TI - Permeability characteristics of cell-membrane pores induced by ostreolysin A/pleurotolysin B, binary pore-forming proteins from the oyster mushroom. AB - Proteins from the oyster mushroom, 15 kDa ostreolysin A (OlyA), and 59 kDa pleurotolysin B (PlyB) with a membrane attack complex/perforin (MACPF) domain, damage cell membranes as a binary cytolytic pore-forming complex. Measurements of single-channel conductance and transmembrane macroscopic current reveal that OlyA/PlyB form non-selective ion-conducting pores with broad, skewed conductance distributions in N18 neuroblastoma and CHO-K1 cell membranes. Polyethylene-glycol 8000 (hydrodynamic radius of 3.78 nm) provides almost complete osmotic protection against haemolysis, which strongly suggests a colloid-osmotic type of erythrocyte lysis. Our data indicate that OlyA/PlyB form transmembrane pores of varied sizes, as other pore-forming proteins with a MACPF domain. PMID- 24211836 TI - Chromatin insulators and long-distance interactions in Drosophila. AB - Data on long-distance enhancer-mediated activation of gene promoters and complex regulation of gene expression by multiple enhancers have prompted the hypothesis that the action of enhancers is restricted by insulators. Studies with transgenic lines have shown that insulators are responsible for establishing proper local interactions between regulatory elements, but not for defining independent transcriptional domains that restrict the activity of enhancers. It has also become apparent that enhancer blocking is only one of several functional activities of known insulator proteins, which also contribute to the organization of chromosome architecture and the integrity of regulatory elements. PMID- 24211838 TI - Loss of CDH1 up-regulates epidermal growth factor receptor via phosphorylation of YBX1 in non-small cell lung cancer cells. AB - Although loss of CDH1 promotes cancer metastasis by disrupting cell-cell adhesion and inducing transcriptional changes, the functional pathways involved in the loss of CDH1 affecting EGFR expression in lung cancer cells still remain largely unknown. In this study, we report that down-regulation of CDH1 promoted EGFR transcription through activation of YBX1. Furthermore, knockdown of CDH1 activated the AKT signaling pathway, and inhibition of AKT suppressed the phosphorylation of YBX1 and the up-regulation of EGFR induced by CDH1 loss. These data demonstrate that loss of CDH1 induces EGFR expression via phospho-YBX1, which is activated through the AKT signaling pathway. PMID- 24211837 TI - Directed polymerase evolution. AB - Polymerases evolved in nature to synthesize DNA and RNA, and they underlie the storage and flow of genetic information in all cells. The availability of these enzymes for use at the bench has driven a revolution in biotechnology and medicinal research; however, polymerases did not evolve to function efficiently under the conditions required for some applications and their high substrate fidelity precludes their use for most applications that involve modified substrates. To circumvent these limitations, researchers have turned to directed evolution to tailor the properties and/or substrate repertoire of polymerases for different applications, and several systems have been developed for this purpose. These systems draw on different methods of creating a pool of randomly mutated polymerases and are differentiated by the process used to isolate the most fit members. A variety of polymerases have been evolved, providing new or improved functionality, as well as interesting new insight into the factors governing activity. PMID- 24211839 TI - Phenotypical characteristics, genetic identification, and antimicrobial sensitivity of Aeromonas species isolated from farmed rainbow trout (Onchorynchus mykiss) in Mexico. AB - In the present study, Aeromonas isolates from diseased and healthy farmed rainbow trout (Oncorhynchus mykiss) in Mexico, were characterized phenotypically and identified to species level by using 16S rDNA RFLP-PCR. A total of 50 isolates were included in the study and 10 Aeromonas species identified. The species A. veronii biovar sobria (22%), A. hydrophila (20%) and A. bestiarum (20%) were the most predominant. All isolates (100%) were resistant to cephalothin. PMID- 24211840 TI - Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. AB - INTRODUCTION: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) seemed to decrease tobacco consumption and craving in nicotine-dependent people without psychiatric disorder or otherwise healthy people. Even if the prevalence of cigarette smoking in schizophrenia patients is high and estimated to be between 45% and 88%, this technique has not been systematically studied in this indication in schizophrenia yet. THE AIM OF THE STUDY: The aim of this study was to test the ability of high frequency (10Hz) rTMS over the left DLPFC to decrease cigarette consumption in schizophrenia patients. METHODS: The study included 35 male schizophrenia patients on stable antipsychotic medication. The patients were divided into two groups: the first (18 patients) were actively stimulated and the second (17 patients) underwent sham (placebo) stimulation. The sham rTMS was administered using a purpose-built sham coil that was identical in appearance to the real coil and made the same noise but did not deliver a substantial stimulus. The rTMS was administered at the stimulation parameters: location (left dorsolateral prefrontal cortex: DLPFC), intensity of magnetic stimulation in % of motor threshold (110%), stimulation frequency (10Hz), number of trains (20), single train duration (10s), inter-train interval (30s), and total number of stimulation sessions (21). In each stimulation session, 2000TMSpulses were given, with a total of 42,000pulses per treatment course. Patients noted the number of cigarettes smoked in the 7days before treatment, during the whole stimulation treatment (21days), and again for a 7-day period after treatment. RESULTS: Cigarette consumption was statistically significantly lower in the actively stimulated patients than in the sham rTMS group as early as the first week of stimulation. No statistically relevant correlations were found in the changes of ongoing negative or depressive schizophrenia symptoms and the number of cigarettes smoked. CONCLUSION: High-frequency rTMS over the left DLPFC has the ability to decrease the number of cigarettes smoked in schizophrenia patients. PMID- 24211841 TI - ECG parameters in children and adolescents treated with aripiprazole and risperidone. AB - Atypical antipsychotics (AP) are increasingly being used in children and adolescents for the treatment of psychiatric disorders. Atypical AP may cause QT prolongation on the electrocardiogram (ECG), which predisposes patients to an increased risk of developing threatening ventricular arrhythmias. Although this phenomenon has been exhaustively reported in adults, few studies investigated the safety of these drugs in pediatric patients. We performed an open-label, prospective study to assess the arrhythmic risk of aripiprazole and risperidone in a pediatric population. A total of 60 patients (55 M/5F, mean age 10.2+2.6 years, range 4-15 years), receiving a new prescription of aripiprazole or risperidone in monotherapy underwent a standard ECG before and after two months from the beginning of antipsychotic treatment. Basal and post-treatment ECG parameters, including mean QT (QTc) and QT dispersion (QTd), were compared within treatment groups. Twenty-nine patients were treated with aripiprazole (mean dosage 7.4+3.1mg/day) and 31 with risperidone (mean dosage 1.5+1mg/day). In our series, no patient exhibited pathological values of QTc or QTd before and after treatment for both drugs. However, treatment with risperidone was associated with a slight increase of both mean QTc and QTd values (407.4+11.9 ms vs 411.2+13.0 ms, p<0.05; and 40.0+4.4 ms vs 44.7+5.5 ms, p<0.001, respectively). Treatment with aripiprazole was associated with no changes of mean QTc, even if a small increase of QTd, (40.6+6.5 ms vs 46.3+7.2 ms, p<0.01) was observed. Although our data suggest a slight effect of aripiprazole and risperidone on ventricular repolarization, it is unlikely that such a change results in clinically relevant effects. The treatment with risperidone and aripiprazole in children with psychiatric disorders is not associated with clinically relevant modifications of QT interval. Caution in prescribing these drugs, however, is necessary in patients with family history of a genetic predisposition to arrhythmias in order to warrant a reliable assessment of drug-induced QT prolongation. PMID- 24211842 TI - Light chain (kappa/lambda) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis. AB - Previous studies demonstrated that antigranulocyte colony-stimulating factor autoantibody (GMAb) was consistently present in patients with autoimmune pulmonary alveolar proteinosis (aPAP), and, thus, represented candidature as a reliable diagnostic marker. However, our large cohort study suggested that the concentration of this antibody was not correlated with disease severity in patients. We found that the kappa/lambda ratio of GMAb was significantly correlated with the degree of hypoxemia. The proportion of lambda-type GMAb per total lambda-type IgG was significantly higher in severely affected patients than those in mildly affected patients, but the proportion of kappa-type was unchanged. The kappa/lambda ratio was significantly correlated with both KL-6 and SP-D, which have been previously reported as disease severity markers. Thus, the light chain isotype usage of GMAb may not only be associated with the severity of aPAP, but may also represent a useful disease severity marker. PMID- 24211844 TI - CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56bright natural killer cells by IFN-gamma secretion. AB - We investigated regulation of human NK cell function by CD27 engagement using a recombinant soluble CD70 protein. CD27 was preferentially expressed on CD56(bright) NK cells, and soluble CD70 protein bound to CD27(+)CD56(bright) NK cells. While soluble CD70 protein enhanced IFN-gamma secretion by CD56(bright) NK cells in the presence of IL-12, it augmented neither cytolytic activity nor proliferation of NK cells. Thus, we next asked if soluble CD70 protein could be used to induce non-cytolytic antiviral activity of NK cells using an in vitro hepatitis C virus (HCV) infection system. Soluble CD70 protein stimulated NK cells to suppress HCV replication by enhancing NK cell IFN-gamma secretion without killing infected cells. Taken together, we demonstrate that CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56(bright) NK cells by IFN-gamma secretion. Thus, this soluble CD70 protein may be useful for the treatment of viral infections such as HCV infection. PMID- 24211845 TI - Combination therapy with anti-CD6 and oral insulin immunization reverses recent onset diabetes in non obese diabetic mice but fails to induce lasting tolerance. PMID- 24211843 TI - Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity. AB - Low-dose tolerance therapy with nucleosomal histone peptide epitopes blocks lupus disease in mouse models, but effect in humans is unknown. Herein, we found that CD4(+)CD25(high)FoxP3(+) or CD4(+)CD45RA(+)FoxP3(low) T-cells, and CD8(+)CD25(+)FoxP3(+) T-cells were all induced durably in PBMCs from inactive lupus patients and healthy subjects by the histone peptide/s themselves, but in active lupus, dexamethasone or hydroxychloroquine unmasked Treg-induction by the peptides. The peptide-induced Treg depended on TGFbeta/ALK-5/pSmad 2/3 signaling, and they expressed TGF-beta precursor LAP. Lupus patients' sera did not inhibit Treg induction. The peptide epitope-induced T cells markedly suppressed type I IFN related gene expression in lupus PBMC. Finally, the peptide epitopes suppressed pathogenic autoantibody production by PBMC from active lupus patients to baseline levels by additional mechanisms besides Treg induction, and as potently as anti-IL6 antibody. Thus, low-dose histone peptide epitopes block pathogenic autoimmune response in human lupus by multiple mechanisms to restore a stable immunoregulatory state. PMID- 24211846 TI - Major infections in a cohort of 120 patients with juvenile-onset systemic lupus erythematosus. AB - In order to describe the incidence and characteristics of major infections in juvenile-onset systemic lupus erythematosus (jSLE), we studied a cohort of 120 patients (51% Hispanic and 28% African American, 49% with renal involvement and 12% with neuropsychiatric manifestations). There were 101 major infections affecting 44 patients (37%) for an incidence of 169/1000 patient-years of follow up. Active disease at jSLE diagnosis, renal involvement, neuropsychiatric manifestations, higher cumulative dose of prednisone, and treatment with cyclophosphamide or mycophenolate mofetil were all associated with major infection (p<0.05). By logistic regression, the combined effect of treatment with cyclophosphamide and cumulative dose of prednisone was associated with major infection (p=0.04). Two patients died, one due to cytomegalovirus infection. Major infection was associated with damage (p=0.004). In conclusion, in a large cohort of jSLE patients, major infections were common, were associated with active disease and its treatment, and resulted in noteworthy morbidity. PMID- 24211848 TI - Emergence of Crimean-Congo hemorrhagic fever in Amreli District of Gujarat State, India, June to July 2013. AB - Crimean-Congo hemorrhagic fever virus (CCHFV) etiology was detected in a family cluster (nine cases, including two deaths) in the village of Karyana, Amreli District, and also a fatal case in the village of Undra, Patan District, in Gujarat State, India. Anti-CCHFV IgG antibodies were detected in domestic animals from Karyana and adjoining villages. Hyalomma ticks from households were found to be positive for CCHF viral RNA. This confirms the emergence of CCHFV in new areas and the wide spread of this disease in Gujarat State. PMID- 24211847 TI - Therapeutic polyclonal human CD8+ CD25+ Fox3+ TNFR2+ PD-L1+ regulatory cells induced ex-vivo. AB - We report that polyclonal CD8regs generated in one week ex-vivo with anti-CD3/28 beads and cytokines rapidly developed suppressive activity in vitro sustained by TGF-beta. In immunodeficient mice, these CD8regs demonstrated a markedly protective, IL-10 dependent activity against a xeno-GVHD. They expressed IL 2Ralpha/beta, Foxp3, TNFR2, and the negative co-stimulatory receptors CTLA-4, PD 1, PD-L1 and Tim-3. Suppressive activity in vitro correlated better with TNFR2 and PD-L1 than Foxp3. Blocking studies suggested that TNF enhanced PD-L1 expression and the suppressive activity of the CD8regs generated. Unlike other polyclonal CD4 and CD8 Tregs, these CD8regs preferentially targeted allogeneic T cells, but they lacked cytotoxic activity against them even after sensitization. Unlike CD4regs, these CD8regs could produce IL-2 and proliferate while inhibiting target cells. If these CD8regs can persist in foreign hosts without impairing immune surveillance, they could serve as a practical remission-inducing product for the treatment of autoimmune diseases, graft-versus-host disease, and allograft rejection. PMID- 24211849 TI - The value of an implicit self-associative measure specific to core beliefs of depression. AB - BACKGROUND AND OBJECTIVES: The present study examined differences in explicit and implicit measures of self-esteem between depressed patients and healthy controls using an indirect measurement procedure especially adapted to measure self-esteem aspects of core beliefs of depression. Furthermore, we examined whether our implicit and explicit self-associative measures were associated with each other and with depressive symptoms, and investigated the effect of a discrepancy between the implicit and explicit measure on depression. METHODS: Participants were 87 depressed patients and 30 healthy controls. The Self-Liking and Self Competence Scale was administered as a measure of explicit self-esteem. A depression-specific variant of the Single Category Implicit Association Test served as a measure of implicit self-esteem. RESULTS: Patients showed significantly lower levels of explicit self-esteem as compared to healthy controls. In spite of our adaptations, no differences were found on the implicit measure. The implicit measure of self-esteem was neither related to the explicit measure nor to depressive symptoms. Furthermore, although both the explicit measure of self-esteem and the difference score of the explicit and implicit measure were related to symptoms of depression, the relation between the explicit measure and depression was found to be significantly stronger. LIMITATIONS: Results should be interpreted with caution because it is not clear yet to what extent these implicit measures really reflect self-esteem. CONCLUSIONS: This study suggests that only the explicit measure of self-esteem - and not the implicit - is related to depression. Future research using well-designed measurement procedures for obtaining implicit and explicit measures could contribute to a better insight in the nature of these constructs. PMID- 24211850 TI - Stress and trauma: BDNF control of dendritic-spine formation and regression. AB - Chronic restraint stress leads to increases in brain derived neurotrophic factor (BDNF) mRNA and protein in some regions of the brain, e.g. the basal lateral amygdala (BLA) but decreases in other regions such as the CA3 region of the hippocampus and dendritic spine density increases or decreases in line with these changes in BDNF. Given the powerful influence that BDNF has on dendritic spine growth, these observations suggest that the fundamental reason for the direction and extent of changes in dendritic spine density in a particular region of the brain under stress is due to the changes in BDNF there. The most likely cause of these changes is provided by the stress initiated release of steroids, which readily enter neurons and alter gene expression, for example that of BDNF. Of particular interest is how glucocorticoids and mineralocorticoids tend to have opposite effects on BDNF gene expression offering the possibility that differences in the distribution of their receptors and of their downstream effects might provide a basis for the differential transcription of the BDNF genes. Alternatively, differences in the extent of methylation and acetylation in the epigenetic control of BDNF transcription are possible in different parts of the brain following stress. Although present evidence points to changes in BDNF transcription being the major causal agent for the changes in spine density in different parts of the brain following stress, steroids have significant effects on downstream pathways from the TrkB receptor once it is acted upon by BDNF, including those that modulate the density of dendritic spines. Finally, although glucocorticoids play a canonical role in determining BDNF modulation of dendritic spines, recent studies have shown a role for corticotrophin releasing factor (CRF) in this regard. There is considerable improvement in the extent of changes in spine size and density in rodents with forebrain specific knockout of CRF receptor 1 (CRFR1) even when the glucocorticoid pathways are left intact. It seems then that CRF does have a role to play in determining BDNF control of dendritic spines. PMID- 24211852 TI - Cutaneous polyarteritis nodosa localized to the arm receiving an infusion of abatacept. PMID- 24211851 TI - Autophagy and apoptosis dysfunction in neurodegenerative disorders. AB - Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders. PMID- 24211853 TI - The influence of various feeding patterns of emodin on growth, non-specific immune responses, and disease resistance to Aeromonas hydrophila in juvenile Wuchang bream (Megalobrama amblycephala). AB - The present study was conducted to evaluate the effect of various feeding patterns of emodin on growth, non-specific immune response, and disease resistance to Aeromonas hydrophila in juvenile Wuchang bream. Healthy Megalobrama amblycephala (initial weight: 3.47 +/- 0.032) were grown in a circulating water system for 8 weeks. Five groups were studied: one control group was fed with a basal diet for eight weeks (Pattern 1, P1), and three treatment groups were fed with a trial diet of 30 mg emodin kg(-1) at one-week (Pattern 2, P2), two-week (Pattern 3, P3), four-week (Pattern 4, P4) intervals. The final treatment group maintained the trial diet for the entire eight-week study duration (Pattern 5, P5). Results indicated that different feeding patterns of emodin significantly influenced the weight gain rate of Wuchang bream (P < 0.05). Fish in the P4 treatment group had significantly higher rates of weight gain (WG) than those in other treatment groups. There were no significant differences in survival rates or feed conversion ratios (FCR) between treatment groups and the control group. White blood cell count (WBC), respiratory burst activity, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) activity were shown to increase at first and then decrease from P3 condition to P5 condition. Fish under P4 treatment showed the most significant improvement of all tested parameters compared to control. Significantly higher levels (P < 0.05) of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were observed in P2 and P4 treatment groups when compared with the control group, while no significant differences were observed in the AST and ALT activity of fish in P2, P3, P4 and P5 treatment groups. In a bacterial challenge experiment with A. hydrophila, fish under P4 and P5 treatment showed lower cumulative mortality than the control group. The results of this study suggest that an initial 4-week feeding interval is recommended for the economic and practical culture of M. amblycephala. PMID- 24211854 TI - Percutaneous treatment of symptomatic aneurysmal bone cyst of L5 by percutaneous injection of osteoconductive material (Cerament). AB - We present a case report of a 33-year-old woman with back pain for several months which was resistant to medical treatment. Thoracolumbar MRI and multidetector CT showed an aneurysmal bone cyst intersecting the body and pedicles of L5. Minimally invasive treatment was performed with percutaneous injection of osteoconductive cement (Cerament) to induce sclerosis and bone remodeling of the bone cyst lesion with an analgesic effect. Before treatment, spinal angiography was performed to exclude arterial afferents. No bone biopsy was done. Under general anesthesia and fluoroscopic guidance, a first vertebroplasty was performed by a bilateral transpedicular approach using the osteoconductive cement followed 2 months later by a second treatment with CT-fluoro-guided direct injection of Cerament. No complications occurred during the procedure. At 4 and 6 months follow-up the MRI/CT showed sclerotic bone remodeling of the walls of the aneurysmal cyst with clinical improvement. PMID- 24211855 TI - Comparison of the biological effects of MMS and Me-lex, a minor groove methylating agent: clarifying the role of N3-methyladenine. AB - N3-methyladenine (3-mA), generated by the reaction of methylating agents with DNA, is considered a highly toxic but weakly mutagenic lesion. However, due to its intrinsic instability, some of the biological effects of the adduct can result from the formation of the corresponding depurination product [an apurinic (AP)-site]. Previously, we exploited Me-lex, i.e. {1-methyl-4-[1-methyl-4-(3 methoxysulfonylpropanamido)pyrrole-2-carboxamido]-pyrrole-2 carboxamido}propane, a minor groove equilibrium binder with selectivity for A/T rich sequences that efficiently reacts with DNA to afford 3-mA as the dominant product, to probe the biology of this lesion. Using human p53 cDNA as a target in a yeast system, a weak increase in mutagenicity was observed in the absence of Mag1 (3 methyladenine-DNA glycosylase 1, mag1), the enzyme devoted to remove 3-mA from DNA. Moreover, a significant increase in mutagenicity occurred in the absence of the enzymes involved in the repair of AP-sites (AP endonucleases 1 and 2, apn1apn2). Since methyl methanesulfonate (MMS) has been extensively used to explore the biological effects of 3-mA, even though it produces 3-mA in low relative yield, we compared the toxicity and mutagenicity induced by MMS and Me lex in yeast. A mutagenesis reporter plasmid was damaged in vitro by MMS and then transformed into wild-type and Translesion Synthesis (TLS) Polzeta (REV3) and Poleta (RAD30) deficient strains. Furthermore, a mag1rad30 double mutant strain was constructed and transformed with the DNA plasmid damaged in vitro by Me-lex. The results confirm the important role of Polzeta in the mutagenic bypass of MMS and Me-lex induced lesions, with Poleta contributing only towards the bypass of Me-lex induced lesions, mainly in an error-free way. Previous and present results point towards the involvement of AP-sites, derived from the depurination of 3-mA, in the observed toxicity and mutagenicity. PMID- 24211856 TI - Photoreceptors in whirler mice show defective transducin translocation and are susceptible to short-term light/dark changes-induced degeneration. AB - Usher syndrome combines congenital hearing loss and retinitis pigmentosa (RP). Mutations in the whirlin gene (DFNB31/WHRN) cause a subtype of Usher syndrome (USH2D). Whirler mice have a defective whirlin gene. They have inner ear defects but usually do not develop retinal degeneration. Here we report that, in whirler mouse photoreceptors, the light-activated rod transducin translocation is delayed and its activation threshold is shifted to a higher level. Rhodopsin mis localization is observed in rod inner segments. Continuous moderate light exposure can induce significant rod photoreceptor degeneration. Whirler mice reared under a 1500 lux light/dark cycle also develop severe photoreceptor degeneration. Previously, we have reported that shaker1 mice, a USH1B model, show moderate light-induced photoreceptor degeneration with delayed transducin translocation. Here, we further show that, in both whirler and shaker1 mice, short-term moderate light/dark changes can induce rod degeneration as severe as that induced by continuous light exposure. The results from shaker1 and whirler mice suggest that defective transducin translocation may be functionally related to light-induced degeneration, and these two symptoms may be caused by defects in Usher protein function in rods. Furthermore, these results indicate that both Usher syndrome mouse models possess a light-induced retinal phenotype and may share a closely related pathobiological mechanism. PMID- 24211857 TI - A randomized controlled trial of the conventional technique versus the no-touch isolation technique for primary tumor resection in patients with colorectal cancer: Japan Clinical Oncology Group Study JCOG1006. AB - A randomized controlled trial is currently being conducted in Japan to demonstrate the superiority of the no-touch isolation technique over the conventional technique for patients with potentially curative colon and rectosigmoid cancer. The conventional technique procedure gives first priority to mobilization of the tumor-bearing segment of the colon, which is followed by central vascular ligation and ligation of other vasculature. Conversely, the no touch isolation technique gives first priority to central vascular ligation, which is followed by mobilization of the tumor-bearing segment of the colon. A total of 850 patients will be enrolled in this trial. The primary endpoint is disease-free survival. Secondary endpoints are overall survival, relapse-free survival, liver metastasis-free survival, mode of recurrence, surgical morbidity, adverse events due to postoperative chemotherapy, serious adverse events and short-term clinical outcomes. PMID- 24211858 TI - Antagonism of the adenosine A2A receptor attenuates akathisia-like behavior induced with MP-10 or aripiprazole in a novel non-human primate model. AB - Akathisia is a subset of the larger antipsychotic side effect profile known as extrapyramidal syndrome (EPS). It is associated with antipsychotic treatment and is characterized as a feeling of inner restlessness that results in a compulsion to move. There are currently no primate models available to assess drug-induced akathisia; the present research was designed to address this shortcoming. We developed a novel rating scale based on both the Barnes Akathisia Rating Scale (BARS) and the Hillside Akathisia Scale (HAS) to measure the objective, observable incidence of antipsychotic-induced akathisia-like behavior in Cebus apella non-human primates (NHPs). To induce akathisia, we administered the atypical antipsychotic aripiprazole (1 mg/kg) or the selective phosphodiesterase 10A (PDE10A) inhibitor MP-10 (1-3 mg/kg). Treatment with both compounds produced significantly greater akathisia scores on the rating scale than vehicle treatment. Characteristic behaviors observed included vocalizations, stereotypies, teeth grinding, restless limb movements, and hyperlocomotion. Adenosine A2A receptor antagonists have previously been shown to be effective in blocking antipsychotic-induced EPS in primates. The selective A2A receptor antagonist, SCH 412348 (10-30 mg/kg), effectively reduced or reversed akathisia like behavior induced by both aripiprazole and MP-10. This work represents the first NHP measurement scale of akathisia and demonstrates that NHPs are responsive to akathisia-inducing agents. As such, it provides a useful tool for the preclinical assessment of putative antipsychotics. In addition, these results provide further evidence of the utility of A2A receptor antagonists for the treatment of antipsychotic-induced movement disorders. PMID- 24211859 TI - Antimicrobial activity of zinc oxide particles on five micro-organisms of the Challenge Tests related to their physicochemical properties. AB - Zinc oxide is commonly used in pharmaceutical products to prevent or treat topical or systemic diseases owing to its antimicrobial properties, but it is scarcely used as preservative in topical formulations. The aim of this work was to investigate the antimicrobial activity of zinc oxide (ZnO) powders on the five microbial strains used for Challenge Tests in order to evaluate this inorganic compound as a preservative in topical formulation and assess relationships between the structural parameters of ZnO particles and their antimicrobial activity. For this purpose, the physicochemical characteristics of three ZnO grades were measured and their antimicrobial efficacy against the following micro organisms - Escherichia coli; Staphylococcus aureus; Pseudomonas aeruginosa; Candida albicans; Aspergillus brasiliensis - was assessed using disc diffusion susceptibility tests and a broth dilution method. The comprehensive dataset of physicochemical characteristics and antimicrobial activities (MIC and MBC) is discussed regarding methodological issues related to the particulate nature of ZnO and structure-activity relationships. Every ZnO grade showed bactericidal and antifungal activity against the five tested micro-organisms in a concentration dependent manner. ZnO particles with smaller size, larger specific area and higher porosity exhibit higher antimicrobial activity. Such trends are related to their mechanisms of antimicrobial activity. PMID- 24211861 TI - A multivariate analysis and statistical model for predicting visual acuity and keratometry one year after cross-linking for keratoconus. AB - PURPOSE: To investigate putative prognostic factors for predicting visual acuity and keratometry 1 year following corneal cross-linking (CXL) for treating keratoconus. DESIGN: Prospective cohort study. METHODS: This study included all consecutively treated keratoconus patients (102 eyes) in 1 academic treatment center, with minimal 1-year follow-up following CXL. Primary treatment outcomes were corrected distance visual acuity (logMAR CDVA) and maximum keratometry (K(max)). Univariable analyses were performed to determine correlations between baseline parameters and follow-up measurements. Correlating factors (P <= .20) were then entered into a multivariable linear regression analysis, and a model for predicting CDVA and K(max) was created. RESULTS: Atopic constitution, positive family history, and smoking were not independent factors affecting CXL outcomes. Multivariable analysis identified cone eccentricity as a major factor for predicting K(max) outcome (beta coefficient = 0.709, P = .02), whereas age, sex, and baseline keratometry were not independent contributors. Posttreatment visual acuity could be predicted based on pretreatment visual acuity (beta coefficient = -0.621, P < .01, R(2) = 0.45). Specifically, a low visual acuity predicts visual improvement. A prediction model for K(max) did not accurately estimate treatment outcomes (R(2) = 0.15). CONCLUSIONS: Our results confirm the role of cone eccentricity with respect to the improvement of corneal curvature following CXL. Visual acuity outcome can be predicted accurately based on pretreatment visual acuity. Age, sex, and K(max) are debated as independent factors for predicting the outcome of treating keratoconus with CXL. PMID- 24211860 TI - An update on anorectal disorders for gastroenterologists. AB - Gastroenterologists frequently encounter pelvic floor disorders, which affect 10% to 15% of the population. The anorectum is a complex organ that collaborates with the pelvic floor muscles to preserve fecal continence and enable defecation. A careful clinical assessment is critical for the diagnosis and management of defecatory disorders and fecal incontinence. Newer diagnostic tools (eg, high resolution manometry and magnetic resonance defecography) provide a refined understanding of anorectal dysfunctions and identify phenotypes in defecatory disorders and fecal incontinence. Conservative approaches, including biofeedback therapy, are the mainstay for managing these disorders; new minimally invasive approaches may benefit a subset of patients with fecal incontinence, but more controlled studies are needed. This mini-review highlights advances, current concepts, and controversies in the area. PMID- 24211862 TI - Hemorrhagic retinal infarction due to inadvertent overdose of cefuroxime in cases of complicated cataract surgery: retrospective case series. AB - PURPOSE: To present 4 patients that developed hemorrhagic retinal infarction attributable to inadvertent overdose of cefuroxime after cataract surgery. DESIGN: Case series. SUBJECTS AND METHODS: Surgery in 4 patients was complicated the posterior capsule was absent or torn-and anterior vitrectomy was performed. Cefuroxime was inadvertently injected at a dose higher than recommended in all 4 cases. RESULTS: Case 1 had hemorrhage in the central and inferior retinal regions, as well as optic atrophy. Case 2 had hemorrhage in the peripapillary and macular regions, as well as optic atrophy. Case 3 had hemorrhage in the peripapillary and inferior retinal regions, as well as macular pucker attributable to fibrovascular formation in the central retinal region. Case 4 had hemorrhage in the peripapillary, macular, and inferior retinal regions. The cefuroxime doses administered to the presented patients were much higher than reported in other cases and resulted in a higher concentration in the vitreous. Consequently, the severity of toxicity was much higher than in other reported cases of cefuroxime-induced toxicity. CONCLUSION: In cases of intracameral cefuroxime overdose, hemorrhagic retinal infarction can develop after cataract surgery. PMID- 24211864 TI - Corneal changes in xeroderma pigmentosum: a clinicopathologic report. AB - PURPOSE: To report the clinicopathologic features of corneal involvement in patients with xeroderma pigmentosum. DESIGN: Retrospective review of corneal histopathology. METHODS: Thirteen corneal specimens of 11 patients with xeroderma pigmentosum who underwent keratoplasty (lamellar/full-thickness) for corneal involvement were studied. Five-micrometer-thick sections were made from all the samples and stained using hematoxylin-eosin and periodic acid-Schiff stains. A light microscopic examination was performed to study the histopathologic changes. RESULTS: The corneal findings on clinical examination were haze, scarring, vascularization, stromal edema, pigment clumps on endothelial surface, and corneal thinning. The histopathologic evaluation revealed changes in all layers of cornea. Epithelial changes seen were intraepithelial edema, fibrosis, epithelial downgrowths, and pannus formation. The Bowman membrane was fragmented or absent. Stroma was characterized by alteration in the lamellar pattern, scarring, edema, loss of keratocytic nuclei, and calcification. The Descemet membrane was thickened to a variable extent in most specimens and there was marked loss of endothelial cells in all. CONCLUSION: Most histologic features are consistent with the previous few reports. The remarkable finding in all corneal specimens was a moderate to severe degree of loss of the endothelial cells. This noteworthy finding supports the ultraviolet (UV) radiation-induced endothelial cell damage in these patients. This has an important clinical implication when planning for anterior lamellar keratoplasty, as endothelial cell density may be subnormal in these patients. PMID- 24211863 TI - Evaluation of a thermosensitive atelocollagen punctal plug treatment for dry eye disease. AB - PURPOSE: To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease. DESIGN: Prospective observational case series. METHODS: The thermosensitive atelocollagen punctal plug was warmed at 37 C, 39 C, 41 C, and 43 C to evaluate the appropriate temperature and time for solidification. Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug. In the conventional implantation group, atelocollagen gel was kept at room temperature for 15 minutes before implantation (27 eyes of 14 patients). In the preheating group, atelocollagen was warmed at 41 C for 8 minutes before implantation (23 eyes of 13 dry eye patients). Strip meniscometry, vital stainings, tear film break-up time (BUT), and symptom scores were evaluated before and 1 month after plug implantation. RESULTS: In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel. The mean fluorescein score in the conventional implantation group significantly improved after treatment (before, 3.5 +/- 2.3 points; after, 2.5 +/- 0.9 points, P < .05). In the preheating group, the mean fluorescein score (before, 3.7 +/- 1.7 points; after, 1.5 +/- 1.2 points), strip meniscometry (before, 0.6 +/- 0.7 mm; after, 1.1 +/- 0.3 mm), BUT (before, 3.2 +/- 0.7 seconds; after, 4.8 +/- 1.0 seconds), and visual analog scale scores (before, 6.6 +/- 1.5 points; after, 4.1 +/- 0.9 points) significantly improved after treatment (P < .05). CONCLUSION: The thermosensitive atelocollagen punctal plug was effective for dry eye treatment. The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug. PMID- 24211865 TI - Intravitreal bevacizumab for nonsubfoveal choroidal neovascularization associated with angioid streaks. AB - PURPOSE: To evaluate the effects of intravitreal bevacizumab injections in the treatment of nonsubfoveal choroidal neovascularization (CNV) associated with angioid streaks. DESIGN: Nonrandomized, interventional, prospective case series. METHODS: Fifteen patients (15 eyes) affected by juxtafoveal or extrafoveal CNV secondary to angioid streaks were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) chart, optical coherence tomography (OCT), and fluorescein angiography (FA). The protocol treatment included a first injection, followed by repeated injections over a 12-month follow-up period on the basis of the detection of new hemorrhage on biomicroscopic examination, any type of fluid on OCT, or presence of leakage on FA. PRIMARY OUTCOME MEASURES: Mean changes in BCVA and proportion of eyes gaining at least 10 letters (2 ETDRS lines) at the end of the follow-up. SECONDARY OUTCOMES: Mean changes of central macular thickness (CMT) and extension to the fovea. RESULTS: Mean BCVA did not change throughout the follow-up period, being 0.2 +/- 0.2 logMAR at baseline and 0.2 +/- 0.3 logMAR at the 12-month examination. A functional improvement of at least 2 ETDRS lines was achieved by 5 eyes (33%), with 3 eyes (20%) gaining 3 lines. Mean CMT at baseline was 215 +/- 13 MUm and 225 +/- 85 MUm at the 12-month examination. Two eyes (13.3%) showed CNV extension to the fovea. CONCLUSIONS: Intravitreal bevacizumab injection can be a beneficial approach for the management of nonsubfoveal CNV secondary to angioid streaks over a 1-year follow-up. PMID- 24211866 TI - The activation of p38 and JNK by ROS, contribute to OLO-2-mediated intrinsic apoptosis in human hepatocellular carcinoma cells. AB - In this study, we describe that a novel synthesized compound, olean-28,13beta olide 2 (OLO-2), exhibits selective cytotoxic activity via inducing apoptosis in human hepatocellular carcinoma (HCC) cell lines but not normal human hepatic cells in vitro. Exposure of human HCC HepG2 cells to OLO-2 results in significant loss of mitochondrial transmembrane potential (DeltaPsim), the release of cytochrome c, the recruitment of B-cell lymphoma 2 (Bcl-2) assaciated X protein (Bax) and the downregulation of Bcl-2. The apoptosis induced by OLO-2 is associated with the activation of caspase-3/9 and the nuclear translocation of apoptosis inducing factor (AIF). Moreover, the increase of phosphorylated p38 and c-Jun N-terminal kinase (JNK) is observed. OLO-2-induced the externalization of phosphatidyl-serine (PS) and the loss of DeltaPsim are blocked by p38 inhibitor SB203580 or JNK inhibitor SP600125. In addition, OLO-2 provokes the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine (NAC) almost completely blocks OLO-2-induced apoptosis and the activation of p38 and JNK. Taken together, the present study demonstrates that OLO-2 exhibits its cytotoxic activity through intrinsic apoptosis via ROS generation and the activation of p38 and JNK. Its potential to be a candidate of anti-cancer agent is worth being further investigated. PMID- 24211868 TI - Mrs Auguste D{eter} demise in 1906 was in Aminoff suffering syndrome. PMID- 24211867 TI - Modulation of Wnt/beta-catenin signaling attenuates periapical bone lesions. AB - Wnt/beta-catenin signaling plays an important role in bone biology. The present study investigated the involvement of Wnt/beta-catenin signaling in rat periapical bone destruction and whether lithium chloride (LiCl), a glycogen synthase kinase-3beta (GSK-3beta) inhibitor, promotes bone restoration. Rat bone marrow mesenchymal cells (BMMSCs) treated with Porphyromonas gingivalis lipopolysaccharide (Pg LPS) showed decreased osteogenic potential through inhibited Wnt/beta-catenin signaling as quantified by Western blot, immunofluorescence, and luciferase reporter assay. Transient Wnt3a treatment in vitro partially restored mineralization and Runx2/Osx and osteocalcin expression in cultures with Pg LPS-induced osteogenic arrest. Prolonged Wnt3a treatment impaired osteogenic commitment. X-ray microtomography showed dramatically enhanced periapical bone formation in rats gavage-fed with LiCl for 2 wks, while continuous LiCl treatment for 4 wks impaired periapical bone healing. LiCl treatment also increased GSK-3beta phosphorylation and osteocalcin expression in periapical tissue. Collectively, these results indicate that Wnt/beta-catenin has dichotomous functions in bone homeostasis. Modulation of this signaling pathway by LiCl may be a potential therapeutic option for bone destruction in endodontic disease. PMID- 24211869 TI - Practices used in Israel by nurses who care during hospitalization for older patients with dementia or who are bedridden. AB - The study's purpose was to examine (a) bedside nurses' care practices when providing care to patients with dementia or those who are physically disabled and (b) the extent to which these actions vary by type of hospital, type of ward, and nurse's characteristics. The sample included 265 nurses in internal medicine and geriatric wards in 2 general hospitals in Israel. The results showed that the most prevalent practices were giving greater attention to these patients, locating them in a room near the nurses' station and asking family members to stay with the patient or to hire paid carers. Use of restraints was more prevalent in patients with dementia than those who were physically disabled. Use of specific practices significantly varied by type of ward and hospital, suggesting that nurses' care practices are more connected with organizational characteristics than other factors. PMID- 24211870 TI - Comparing tomographic EEG neurofeedback and EMG biofeedback in children with attention-deficit/hyperactivity disorder. AB - Two types of biofeedback (BF), tomographic electroencephalogram (EEG) neurofeedback (NF) and electromyographic biofeedback (EMG-BF), both with phasic and tonic protocols, were compared for treatment effects and specificity in attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD trained their brain activity in the anterior cingulate cortex (ACC), and twelve trained activity of arm muscles involved in fine motor skills. In each training session, resting state 24-channel EEG and training performances were recorded. Both groups showed similar behavioral improvements and artifact reduction in selected conditions, with no significant advantages despite medium effect sizes on primary outcomes for NF. Only the EMG-BF group, however, showed clear improvement in training regulation performance, and specific motor coordination effects. The NF group tended to present individual normalization of trained frequency bands in the ACC during rest across training. The results provide evidence for some specific effects in our small sample, albeit only to a small extent. PMID- 24211871 TI - Muramyl dipeptide potentiates staphylococcal lipoteichoic acid induction of cyclooxygenase-2 expression in macrophages. AB - Gram-positive bacteria contain lipoteichoic acid (LTA) and peptidoglycan (PGN) layers, both of which are considered as major virulence factors associated with inflammation. Cyclooxygenase-2 (COX-2) plays an important role in the inflammation by generating prostaglandins at infections. Since LTA and PGN are thought to cooperate in the establishment of inflammation, we examined the ability of staphylococcal LTA (Sa.LTA) to induce COX-2 expression in the presence of muramyl dipeptide (MDP), which is the minimal structural unit of PGN required for inflammation, in macrophages. While MDP failed to induce COX-2 expression, Sa.LTA alone was sufficient to induce COX-2 production. Treatment with MDP enhanced Sa.LTA-induced COX-2 and prostaglandin E2 production. The cooperative effect between Sa.LTA and MDP was not observed in COX-2 expression by macrophages derived from Toll-like receptor 2 (TLR2)- or nucleotide-binding oligomerization domain 2 (NOD2)-deficient mice. In addition, MDP enhanced Sa.LTA-induced activation of the transcription factors NF-kappaB and CRE, which are known to modulate COX-2 gene transcription. Conclusively, these results suggest that MDP and Sa.LTA cooperatively induce inflammatory response by overproducing COX-2 through NOD2 and TLR2. PMID- 24211872 TI - Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy. AB - The conflict between the needs to encode both a protein (impaired by non synonymous mutation), and nucleic acid structure (impaired by synonymous or non synonymous mutation), can sometimes be resolved in favour of the nucleic acid because its structure is critical for a selectively advantageous genome-wide activity--recombination. However, above a sequence difference threshold, recombination is impaired. It may then be advantageous for new species to arise. Building on the work of Grantham and others critical of the neutralist viewpoint, heuristic support for this hypothesis emerged from studies of the base composition and structure of retroviral genomes. The extreme enrichment in the purine A of the RNA of human immunodeficiency virus (HIV-1), parallels the mild purine-loading of the RNAs of most organisms, for which there is an adaptive explanation--immune evasion. However, human T cell leukaemia virus (HTLV-1), with the potential to invade the same host cell, shows extreme enrichment in the pyrimidine C. Assuming the low GC% HIV and the high GC% HTLV-1 to share a common ancestor, it was postulated that differences in GC% had arisen to prevent homologous recombination between these emerging lentiviral species. Sympatrically isolated by this intracellular reproductive barrier, prototypic HIV-1 seized the AU-rich (low GC%) high ground (thus committing to purine A rather than purine G). Prototypic HTLV-1 forwent this advantage and evolved an independent evolutionary strategy--similar to that of the GC%-rich Epstein-Barr virus--profound latency maintained by transcription of one purine-rich mRNA. The evidence supporting these interpretations is reviewed. PMID- 24211873 TI - SitA contributes to the virulence of Klebsiella pneumoniae in a mouse infection model. AB - Klebsiella pneumoniae is an opportunistic pathogen, which causes a wide range of nosocomial infections. Recently, antibiotic resistance makes K. pneumoniae infection difficult to deal with. Investigation on virulence determinants of K. pneumoniae can provide more information about pathogenesis and unveil new targets for treatment or vaccine development. In this study, SitA, a Fur-regulated divalent cation transporter, was found significantly increased when K. pneumoniae was cultured in a nutrient-limited condition. A sitA-deletion strain (DeltasitA) was created to characterize the importance of SitA in virulence. DeltasitA showed higher sensitivity toward hydroperoxide than its parental strain. In a mouse intraperitoneal infection model, the survival rate of mice infected with DeltasitA strain increased greatly when compared with that of mice infected with the parental strain, suggesting that sitA deletion attenuates the bacterial virulence in vivo. To test whether DeltasitA strain is a potential vaccine candidate, mice were immunized with inactivated bacteria and then challenged with the wild-type strain. The results showed that using DeltasitA mutant protected mice better than using the wild-type strain or the capsule-negative congenic bacteria. In summary, SitA was found being important for the growth of K. pneumoniae in vivo and deleting sitA might be a potential approach to generate vaccines against K. pneumoniae. PMID- 24211875 TI - Frontiers in biomedical engineering and biotechnology. AB - The 2nd International Conference on Biomedical Engineering and Biotechnology (iCBEB 2013), held in Wuhan on 11-13 October 2013, is an annual conference that aims at providing an opportunity for international and national researchers and practitioners to present the most recent advances and future challenges in the fields of Biomedical Information, Biomedical Engineering and Biotechnology. The papers published by this issue are selected from this conference, which witnesses the frontier in the field of Biomedical Engineering and Biotechnology, which particularly has helped improving the level of clinical diagnosis in medical work. PMID- 24211876 TI - Mitral valve function following ischemic cardiomyopathy: a biomechanical perspective. AB - Ischemic mitral valve (MV) is a common complication of pathologic remodeling of the left ventricle due to acute and chronic coronary artery diseases. It frequently represents the pathologic consequences of increased tethering forces and reduced coaptation of the MV leaflets. Ischemic MV function has been investigated from a biomechanical perspective using finite element-based computational MV evaluation techniques. A virtual 3D MV model was created utilizing 3D echocardiographic data in a patient with normal MV. Two types of ischemic MVs containing asymmetric medial-dominant or symmetric leaflet tenting were modeled by altering the configuration of the normal papillary muscle (PM) locations. Computational simulations of MV function were performed using dynamic finite element methods, and biomechanical information across the MV apparatus was evaluated. The ischemic MV with medial-dominant leaflet tenting demonstrated distinct large stress distributions in the posteromedial commissural region due to the medial PM displacement toward the apical-medial direction resulting in a lack of leaflet coaptation. In the ischemic MV with balanced leaflet tenting, mitral incompetency with incomplete leaflet coaptation was clearly identified all around the paracommissural regions. This computational MV evaluation strategy has the potential for improving diagnosis of ischemic mitral regurgitation and treatment of ischemic MVs. PMID- 24211877 TI - Measurement of salivary cortisol by a chemiluminescent organic-based immunosensor. AB - A highly sensitive chemiluminescent immunoassay (CLIA) using a sensitive organic photodetector was developed to detect human cortisol, an important biomarker for stress-related diseases. The developed CLIA was performed onto gold-coated glass chips, on which anti-cortisol antibodies were immobilised and chemiluminescent horseradish peroxidase-luminol-peroxide reactions were generated. Using cortisol spiked artificial saliva samples, the CLIA biosensor showed a linear range of detection between 0.1 ng/mL and 175 ng/mL and a detection limit of 80 pg/mL. The sensor response was highly specific to cortisol and did not vary significantly between assays. The results indicate the potential clinical application of the CLIA sensor. Furthermore, the simple layered structure of the organic photodetector may encourage the realisation of integrated optical biosensors for point-of-use measurement of salivary cortisol levels. PMID- 24211878 TI - Urea biosensor based on an extended-base bipolar junction transistor. AB - In this study, a urea biosensor was prepared by the immobilization of urease onto the sensitive membrane of an extended-base bipolar junction transistor. The pH variation was used to detect the concentration of urea. The SnO2/ITO glass, fabricated by sputtering SnO2 on the conductive ITO glass, was used as a pH sensitive membrane, which was connected with a commercial bipolar junction transistor device. The gels, fabricated by the poly vinyl alcohol with pendent styrylpyridinium groups, were used to immobilize the urease. This readout circuit, fabricated in a 0.35-um CMOS 2P4M process, operated at 3.3V supply voltage. This circuit occupied an area of 1.0 mm * 0.9 mm. The dynamic range of the urea biosensor was from 1.4 to 64 mg/dl at the 10 mM phosphate buffer solution and the sensitivity of this range was about 65.8 mV/pUrea. The effect of urea biosensors with different pH values was considered, and the characteristics of urea biosensors based on EBBJT were described. PMID- 24211879 TI - Interactive cell segmentation based on phase contrast optics. AB - Cell segmentation in phase contrast microscopy images lays a crucial foundation for numerous subsequent computer-aided cell image analysis, but it encounters many unsolved challenges due to image qualities and artifacts caused by phase contrast optics. Addressing the unsolved challenges, the authors propose an interactive cell segmentation scheme over phase retardation features. After partitioning the images into phase homogeneous atoms, human annotations are propagated to unlabeled atoms over an affinity graph that is learned based on discrimination analysis. Then, an active query strategy is proposed for which the most informative unlabeled atom is selected for annotation, which is also propagated to the other unlabeled atoms. Cell segmentation converges to quality results after several rounds of interactions involving both the user's intentions and characteristics of image features. Experimental results demonstrate that cells with different optical properties are well segmented via the proposed approach. PMID- 24211880 TI - New clinical failure mode triggered by a new coronary stent design. AB - Longitudinal stent compression (LSC) is a new failure mode not previously observed in coronary stents. This phenomenon occurs when the physician tries to cross the deployed stent with other devices. While this phenomenon has been observed with a number of stent designs, it seems more common with the Element stent. A computational LSC model using finite element analysis was developed. Computational simulations were performed on two representative coronary stents in the current market resembling Element and Endeavor in attempts to quantify individual contribution of the stent design pattern and connector number on LSC. Simulation results show that the connector number plays the most significant role in the development of the LSC issue. The LSC could be easily tripled for the Element stent simply by increasing the connector number from two to three. The stent design pattern plays a secondary role in LSC. The LSC could be improved by up to 30% when the design pattern changes from the offset peak-to-peak design (Element) to the peak-to-peak design (Endeavor). Conclusions obtained from this paper may help clinical stent selection and future stent design optimization to reduce the risk associated with longitudinal stent compression. PMID- 24211881 TI - Single-slice reconstruction method for helical cone-beam differential phase contrast CT. AB - X-ray phase-contrast computed tomography (PC-CT) can provide the internal structure information of biomedical specimens with high-quality cross-section images and has become an invaluable analysis tool. Here a simple and fast reconstruction algorithm is reported for helical cone-beam differential PC-CT (DPC-CT), which is called the DPC-CB-SSRB algorithm. It combines the existing CB SSRB method of helical cone-beam absorption-contrast CT with the differential nature of DPC imaging. The reconstruction can be performed using 2D fan-beam filtered back projection algorithm with the Hilbert imaginary filter. The quality of the results for large helical pitches is surprisingly good. In particular, with this algorithm comparable quality is obtained using helical cone-beam DPC-CT data with a normalized pitch of 10 to that obtained using the traditional inter row interpolation reconstruction with a normalized pitch of 2. This method will push the future medical helical cone-beam DPC-CT imaging applications. PMID- 24211882 TI - Automatic detection of microcalcifications using mathematical morphology and a support vector machine. AB - In this paper, we propose a novel method for the detection of microcalcifications using mathematical morphology and a support vector machine (SVM). First, the contrast in the original mammogram was improved by gamma correction and two carefully designed structural elements were used to enhance any microcalcifications. Next, the potential regions were extracted using our proposed dual-threshold technique. Finally, a SVM classifier was used to reduce the number of false positives. The performance of the proposed method was evaluated using the MIAS database. The experimental results demonstrated the efficiency and effectiveness of our method. PMID- 24211883 TI - A novel liposomal nanomedicine for nitric oxide delivery and breast cancer treatment. AB - Breast cancer is the most common type of cancer occurring among women in the United States. Nitric oxide (NO) is endogenous signaling molecules that regulate biological processes. NO has the potential to induce either cancer progression or cancer cell apoptosis depending on intra-tumoral NO concentration. High levels of NO have a cytotoxic effect on cancer cells. A novel cytotoxic gas delivery system has been developed using NO-loaded echogenic liposomes (ELIP) for breast cancer treatment. Empty ELIP and NO-ELIP were prepared using the previously developed freezing-under-pressure method with modified lipid composition. Echogenicity of NO-ELIP was measured to determine the stability of NO-ELIP. Two types of breast cancer cell (BCC) lines, MDA-MB-231 and MDA-MB-468, were utilized. MTT assay was performed after NO-ELIP treatment to determine BCC viability. Echogenicity data demonstrated improved stability of NO-ELIP with the use of BSA for resuspension of NO-ELIP. Cell death induced by NO-ELIP was not from lipid cytotoxicity but from NO. The cytotoxic effect of NO-ELIP on BCC was highly dependent on NO-ELIP concentration. NO-ELIP in concentration of 1.0-2.0 mg/ml induced dramatically decreased BCC viability. This novel cytotoxic gas delivery nanomedicine using liposomal carriers, NO-ELIP, has the potential to provide improved therapeutic effect for breast cancer treatment. PMID- 24211884 TI - A resident's behavior simulation model for nursing home healthcare services. AB - The design of elaborate healthcare services is becoming increasingly difficult in today's nursing home. In this work, we develop a model that simulates the nursing home residents' behavior to assist the facility planners in making fair and feasible management. Since a series of activities constituted one behavior, every activity is performed in a time interval and then starts next activity consequently. Whether the resident's activity posed at any particular state, its future behavior is always having the same occurrence probability regardless of how it positioned in that state. This simulation model used exponential distribution to produce the stochastic activity interval for each activity. The activity transitions can be formalized through a randomized probability with respect to each activity frequency (AF). In the simulation model, the characteristics of nursing home residents' activities can be generated to simulate a large scaled resident's behavior and aid the facility managers in providing higher quality of healthcare services. PMID- 24211885 TI - Identification of microfluidic two-phase flow patterns in lab-on-chip devices. AB - This work describes a capacitive sensor for identification of microfluidic two phase flow in lab-on-chip devices. With interdigital electrodes and thin insulation layer utilized, this sensor is capable of being integrated with the microsystems easily. Transducing principle and design considerations are presented with respect to the microfluidic gas/liquid flow patterns. Numerical simulation results verify the operational principle. And the factors affecting the performance of the sensor are discussed. Besides, a feasible process flow for the fabrication is also proposed. PMID- 24211886 TI - 4D-CT reconstruction based on pulmonary average CT values. AB - To date, commercial 4D-CT systems typically depend on an external respiratory monitoring device. Immobilizing patients in a thermoplastic mask while receiving radiotherapy may result in a failure of 4D-CT reconstruction. The aim of this study is to investigate the feasibility of 4D-CT reconstruction based on a method using pulmonary average CT values (ACV) without an external respiratory monitoring device. The ACV of the whole lung assumes cyclical variation during respiration. Phases of CT images were identified by calculating the ACV over time. Subsequently, five sets of 4D-CT images based on a Real-time Position Management (RPM) system were selected to verify the ACV method. The entire lung CT datasets of another sixteen free-breathing patients were acquired in Cine scan mode for multiple couch positions. The phase of every CT image was identified and re-sorted into different phase 4D-CT volumes by analyzing the time dependence of the corresponding ACVs. This paper demonstrates the ACV method using the 4D-CT data sets based on the RPM system. Convenient and reliable 4D-CT reconstruction can be accomplished without any external respiratory monitoring device using ACVs. PMID- 24211887 TI - Poly-silicon nanowire sensor for sodium chloride concentration measurement. AB - In this paper, the poly-Si nanowire sensor was fabricated by top-down technique for sodium chloride concentration measurement. The results showed that the smallest threshold voltage and the best resolution were 1.65 V and 0.41 MUM, respectively. Furthermore, the sensor can be reused more than 50 times which maintained acceptable performance and showed good linearity of the calibration within wide range of the concentration. Based on these results, it can be concluded that the proposed sensor has great potential to be used for measuring complicated sample with suitable modification on the surface of nanowires. PMID- 24211888 TI - Performance improved method for subtracted blood volume spectrometry using empirical mode decomposition. AB - Subtracted blood volume spectrometry (SBVS) can eliminate the background information in near infrared spectroscopy (NIRS) noninvasive biochemical sensing. However, the spectrum obtained by this method is accompanied by serious noises which are to the disadvantage of the calibration models. Empirical mode decomposition (EMD) was applied to restrict the noises in order to improve the performance of subtracted blood volume spectrometry. Certain criteria were used to evaluate the performance of the method, such as the average correlation coefficient, and the average and standard deviation of the Euclidean distance. EMD was applied to three subtracted spectra with different DeltaL, and the criteria were calculated accordingly. All of the criteria were improvement. Especially for the subtracted spectra with DeltaL=0.5mm, the correlation coefficient increased from 0.9970 to 0.9999, the average Euclidean distance decreased from 0.0265 to 0.0118, and the standard deviation of the Euclidean distance decreased from 0.0148 to 0.0033 after EMD filtering. The PLS models of the processed spectra were promoted as well. These preliminary results suggest that EMD is a promising means of improving the performance of subtracted blood volume spectrometry. PMID- 24211889 TI - Application of the dual-tree complex wavelet transform in biomedical signal denoising. AB - In biomedical signal processing, Gibbs oscillation and severe frequency aliasing may occur when using the traditional discrete wavelet transform (DWT). Herein, a new denoising algorithm based on the dual-tree complex wavelet transform (DTCWT) is presented. Electrocardiogram (ECG) signals and heart sound signals are denoised based on the DTCWT. The results prove that the DTCWT is efficient. The signal-to-noise ratio (SNR) and the mean square error (MSE) are used to compare the denoising effect. Results of the paired samples t-test show that the new method can remove noise more thoroughly and better retain the boundary and texture of the signal. PMID- 24211890 TI - Flow visualization in the outflow cannula of an axial blood pump. AB - The properties of blood flow in the outflow cannula of an axial blood pump play a critical role in potential thrombus formation and vascular injury. In this study, an in vitro flow visualization technique using particle image velocimetry (PIV) was applied to investigate the flow characteristics in the outflow cannula of a FW-2 model axial pump. The two-dimensional (2-D) flow field in the axial central section and the three-dimensional (3-D) flow field in the whole outflow cannula were examined with the PIV system. Tests were carried out with a blood-mimic working fluid in the axial pump at a rotational speed of 8500 +/- 20 rpm with a flow rate of 5 L/min. The velocity distribution in the outflow cannula was analyzed to evaluate the flow characteristics. There was no backflow or stagnant flow in the tested area, while the flow velocity rapidly increased outside the boundary layer. A spiral flow was observed near the boundary layer, but this was worn off within the tested area. Based on the results, hemolysis and thrombus formation in the cannula, and injury to aortic endothelium are unlikely to occur due to spiral flow. PMID- 24211891 TI - Research and development of compact wrist rehabilitation robot system. AB - Compact rehabilitation robot system which can support movement of the wrist of patients has been developed. The robot system can detect and analyze the patient's intention to move the wrist by such a biological signal as muscle potential, then, assist the wrist exercise of patients. Also, both-wrist rehabilitation robot system by mirror effect has been successfully developed for practical use in the hospital and at home. PMID- 24211892 TI - Texture feature extraction based on wavelet transform and gray-level co occurrence matrices applied to osteosarcoma diagnosis. AB - Osteosarcoma is the most common malignant bone tumor among children and adolescents. In this study, image texture analysis was made to extract texture features from bone CR images to evaluate the recognition rate of osteosarcoma. To obtain the optimal set of features, Sym4 and Db4 wavelet transforms and gray level co-occurrence matrices were applied to the image, with statistical methods being used to maximize the feature selection. To evaluate the performance of these methods, a support vector machine algorithm was used. The experimental results demonstrated that the Sym4 wavelet had a higher classification accuracy (93.44%) than the Db4 wavelet with respect to osteosarcoma occurrence in the epiphysis, whereas the Db4 wavelet had a higher classification accuracy (96.25%) for osteosarcoma occurrence in the diaphysis. Results including accuracy, sensitivity, specificity and ROC curves obtained using the wavelets were all higher than those obtained using the features derived from the GLCM method. It is concluded that, a set of texture features can be extracted from the wavelets and used in computer-aided osteosarcoma diagnosis systems. In addition, this study also confirms that multi-resolution analysis is a useful tool for texture feature extraction during bone CR image processing. PMID- 24211893 TI - The feasibility of mapping dose distribution of 4DCT images with deformable image registration in lung. AB - Calculating an accurate cumulative dose through individual phases for four dimensional computed tomography (4DCT) images from the lung is time-consuming. Although the dose distribution of different phases is similar, copying the dose distribution of one phase directly to another phase would yield a dosimetric error of approximately 4% without further optimization. To reduce the dosimetric error, three-dimensional B-spline elastic deformable image registration (DIR) was used to quickly obtain a relatively accurate cumulative dose of 4DCT images acquired from ten lung cancer patients. The dose distribution of the end expiration phase was mapped to the end-inspiration phase using DIR. The mapped dose in the end-inspiration phase was then compared with the directly copied dose by analysis (3cm/3%) and the t-test. The results showed that optimization using DIR was significantly better in the average pass rate (by 0.6-4.7%). Our results indicate it is feasible to map the dose distribution of 4DCT images in lung with DIR, and that the motion amplitude of individual respiratory and different DIR algorithms affect the differences between the mapped and actual dose. PMID- 24211894 TI - Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair. AB - Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER. PMID- 24211895 TI - Evaluation of breast cancer chemotherapy efficacy with multifractal spectrum analysis of magnetic resonance image. AB - Multifractal spectrum analysis of dynamic contrast enhanced (DCE) breast MR images was used to establish a new quantitative analysis method for solid tumor blood perfusion and to explore its applicability in evaluating efficacy of breast cancer chemotherapy. Five randomly selected patients suffering from newly diagnosed malignant breast nodule lesions were enrolled in this study, and four of them were treated with neoadjuvant chemotherapy. Their DCE breast MR images were collected before and after treatment. Chemotherapeutic efficacy was analyzed using international response evaluation criteria for solid tumors (RECIST). Sandbox method for statistical number density was employed to measure and calculate multifractal spectra of DCE breast MR images with spatiotemporal characteristics. Multifractal spectral data of malignant lesions before and after chemotherapy were compared. Multifractal spectra of malignant lesions show an asymmetric bell-shape. Chemotherapy efficacy was assessed to be partial remission (PR) for three patients and their multifractal spectral width significantly increased after chemotherapy while to be stable disease (SD) for other patient and of her changed slightly. Multifractal spectral width correlates with blood supply condition of tumor lesion before and after chemotherapy, providing a potential suitable characteristic parameter for evaluating chemotherapeutic efficacy quantitatively. PMID- 24211896 TI - The influence of protein concentration on the biotribological properties of the stem-cement interface. AB - The stem-cement interface in total hip replacement experiences fretting wear following debonding under cyclical physiological loading. However, the influence of protein concentration on the biotribological properties of this interface has not been well taken into consideration. In the present study, a series of fretting frictional tests were performed using polished Ti6Al4V and bone cement, lubricated by bovine serum albumin solutions of different concentrations (5%, 30%, and 75%). Surface characterizations of Ti6Al4V pins were conducted by optical interferometer, scanning electron microscope, and Raman spectroscopy. The results show that the friction coefficient decreases with the increase of protein concentration, although the difference is not significant. In addition, bovine serum albumin is adsorbed onto Ti6Al4V surface, forming a protective film to prevent the metal substrate from wear. The elemental and spectroscopic analyses of the film confirm the presence of protein molecules adsorbed on Ti6Al4V surface, with a thickness of 2.5 MUm. It is indicated from this study that fretting wear at the stem-cement interface can be postponed by promotion of protein adsorption on the metal surface. PMID- 24211897 TI - Effect of curcumin on down-expression of thrombospondin-4 induced by oxidized low density lipoprotein in mouse macrophages. AB - This study was designed to investigate the effect of curcumin on the expression of thrombospondin-4 (THBS-4) in mouse macrophages treated with oxidized low density lipoprotein (oxLDL). The mouse macrophage cell line ANA-1 was treated with oxLDL. Cell viability was measured by MTT assay. ANA-1 cells were divided into five groups: control group, model group, 5 MUM curcumin group, 15 MUM curcumin group and 25 MUM curcumin group. The gene and protein expression levels of THBS-4 in each group were determined by real-time quantitative polymerase chain reaction (PCR) and western blotting, respectively. MTT assay showed that curcumin concentrations up to 25 MUM and oxLDL concentrations up to 20 MUg/ml had no significant cytotoxic effects on macrophages at 24 h. Real-time quantitative PCR revealed that THBS-4 mRNA expression was markedly reduced by stimulation with oxLDL, but subsequently significantly increased by treatment with curcumin. Western blotting confirmed that curcumin (5, 15, and 25 MUM) significantly prevented the decrease in THBS-4 expression induced by oxLDL (20 MUg/ml) in macrophages. Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin. PMID- 24211898 TI - Creep bulging deformation of intervertebral disc under axial compression. AB - The internal hydrostatic pressure (IHP) of the intervertebral disc is the functional and physiological basis of the spine. Disc bulging is a direct effect of increased IHP and can be used to evaluate the IHP without destroying the structure of the disc. Disc tissue engineering is a developing field but more data on the properties of normal discs are required for evaluation of possible graft materials. However, very little data is available concerning bulge distribution along the normal disc surface under creep. METHODS: Fifteen motion segment specimens of ovine IVD were used to analyze axial creep, and disc bulging deformations of 5 markers on the surface were measured and analyzed. FINDINGS: The maximum radial bulging rate was 2.78%+/- 1.09% and the position at which the maximum radial deformation occurred was found to be below the midline of the disc during all levels of loading. The results showed that deformations occurred in the order vertical, radial, circumferential. INTERPRETATION: Disc bulging during creep is a very important biomechanical response, affecting spinal functions. The deformation regularities of the disc surface were identified and may help supply important basic data for disc tissue engineering. PMID- 24211899 TI - Reflection coefficient detection of simulation models for microwave imaging simulation system. AB - The study was conducted based on two objectives as framework. The first objective is to determine the point of microwave signal reflection while penetrating into the simulation models and, the second objective is to analyze the reflection pattern when the signal penetrate into the layers with different relative permittivity, epsilonr. Thus, several microwave models were developed to make a close proximity of the in vivo human brain. The study proposed two different layers on two different characteristics models. The radii on the second layer and the corresponding antenna positions are the factors for both models. The radii for model 1 is 60 mm with an antenna position of 10 mm away, in contrast, model 2 is 10 mm larger in size with a closely adapted antenna without any gap. The layers of the models were developed with different combination of materials such as Oil, Sandy Soil, Brain, Glycerin and Water. Results show the combination of Glycerin + Brain and Brain + Sandy Soil are the best proximity of the in vivo human brain grey and white matter. The results could benefit subsequent studies for further enhancement and development of the models. PMID- 24211900 TI - The pulse wave analysis of normal pregnancy: investigating the gestational effects on photoplethysmographic signals. AB - OBJECTIVE: Normal pregnancy is associated with profound alterations in the maternal cardiovascular system and PPG represents a sensitive and convenient technique capable of tracking changes in the pulsatile function of arteries. The aim of this study was to investigate the effects of maternal cardiovascular alterations on the finger tip photoplethysmography (PPG) during normal gestation. METHODS: Thirty five healthy pregnant women were studied at each trimester of pregnancy and again on gestational age using PPG signals, peripheral blood pressure (BP) and heart rate (HR). RESULTS: Comparing with nonpregnant controls, several characteristic differences in PPG derived parameters and morphologies occurred in the pregnant. PAI, RI, PTT as well as AUC1 and Y1 of bcAUC1 were different and significant difference had been found in second and third trimester, despite little change in the peripheral blood pressure. The mean heart rate increased linearly with gestational age. CONCLUSION: This study has confirmed that normal pregnancy is associated with profound alterations in PPG signals occurred principally as a result of maternal cardiovascular adaptation and PPG-based noninvasive assessment of cardiovascular activities is feasible throughout pregnancy. Using this technique we demonstrated a delay in wave reflection within the arterial tree and a reduction in magnitude of arterial wave reflections in normal pregnancy which is consistent with previous observations and the known cardiovascular changes of pregnancy. PMID- 24211901 TI - Multimodal medical image fusion using improved multi-channel PCNN. AB - Multimodal medical image fusion is a method of integrating information from multiple image formats. Its aim is to provide useful and accurate information for doctors. Multi-channel pulse coupled neural network (m-PCNN) is a recently proposed fusion model. Compared with previous methods, this network can effectively manage various types of medical images. However, it has two drawbacks: lack of control to feed function and low-level automation. The improved multi-channel PCNN proposed in this paper can adjust the impact of feed function by linking strength and adaptively compute the weighting coefficients for each pixel. Experimental results demonstrated the effectiveness of the improved m-PCNN fusion model. PMID- 24211902 TI - A novel biofuel cell based on electrospun collagen-carbon nanotube nanofibres. AB - The paper demonstrates a novel glucose/O2 biofuel cell (BFC) based on the electrospun collagen-SWNTs nanofibres with the glucose oxidase (GOD) as the anodic biocatalysts and the laccase as the cathodic biocatalysts. With an average diameter of about (260+/-95) nm, the electrospun collagen-SWNTs nanofibres exhibited smooth surfaces. The collagen-SWNTs nanofibres modified electrode showed good electron transfer behavior, because of the properties of SWNTs and the three-dimensional reticular structure of the electrospun nanofibers. The GOD and laccase, immobilized in the collagen-SWNTs nanofibres, exhibited good catalytic activity towards glucose oxidation and oxygen reduction through mediators of ferrocene monocarboxylic acid (FMCA) and 2,2'-azinobis (3 ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), respectively. The maximum power density of the assembled glucose/O2 BFC based on the electrospun collagen-SWNTs nanofibres was ca. 14.3 MUW/cm2. Moreover, more than 50% of the initial value remained after continuous operation of 100 h. The results indicated the potential to apply the electrospun collagen-SWNTs nanofibres for novel BFC device. PMID- 24211903 TI - Sparse coding induced transfer learning for HEp-2 cell classification. AB - Automated human larynx carcinoma (HEp-2) cell classification is critical for medical diagnosis. In this paper, we propose a sparse coding-based unsupervised transfer learning method for HEp-2 cell classification. First, the low level image feature is extracted for visual representation. Second, a sparse coding scheme with the Elastic Net penalized convex objective function is proposed for unsupervised feature learning. At last, a Support Vector Machine classifier is utilized for model learning and predicting. To our knowledge, this work is the first to transfer the human-crafted visual feature, sensitive to the variation of appearance and shape during cell movement, to the high level representation which directly denotes the correlation of one sample and the bases in the learnt dictionary. Therefore, the proposed method can overcome the difficulty in discriminative feature formulation for different kinds of cells with irregular and changing visual patterns. Large scale comparison experiments will be conducted to show the superiority of this method. PMID- 24211904 TI - Activity analysis of trunk and leg muscles during whole body tilt exercise. AB - The objectives were to assess the trunk and leg muscle activities during the trunk tilt exercise by a 3D dynamic exercise device capable of active and passive movements, to study the evaluation of Root Mean Squire (RMS), and to investigation the influence of the trunk positions on these muscle activities. Eighteen healthy volunteers were selected. None of the subjects had any history of lumber and trunk muscle problems. Rotation capability was enabled for the investigation of A (anterior), R (right), P (posterior), L (left), AR (anterior right), AL (anterior left), PR (posterior right), PL (posterior left) tilt directions. EMG signals of trunk (rectus abdominis, external obliques, latissimus dorsi, erector spinae) muscles and leg (rectus femoris, Biceps femoris, Tibialis Anterior, gastrocnemius) muscles were taken out. Root Mean Squire (RMS) values were calculated. The results of this study indicate that different exercise patterns can be applied depending on the exercise types, which are appropriate and necessary to each user. We believe that the human body can be maintained in equilibrium through the interaction between the position and movement execution of the human body, contributing to the improvement of body balance control. Further quantitative data collection and analysis related to the development of various spinal stabilization exercise programs is required. In the near future, we will conduct a study concerning the effects of trunk tilt exercise in active and passive modes on the strength of the tilting muscles and postural balancing ability. PMID- 24211905 TI - Influence of timing algorithm on brachialankle pulse wave velocity measurement. AB - The baPWV measurement is a non-invasive and convenient technique in an assessment of arterial stiffness. Despite its widespread application, the influence of different timing algorithms is still unclear. The present study was conducted to investigate the influence of six timing algorithms (MIN, MAX, D1, D2, MDP and INS) on the baPWV measurement and to evaluate the performance of them. Forty-five CAD patients and fifty-five healthy subjects were recruited in this study. A PVR acquisition apparatus was built up for baPWV measurement. The baPWV and other related parameters were calculated separately by the six timing algorithms. The influence and performance of the six algorithms was analyzed. The six timing algorithms generate significantly different baPWV values (left: F=29.036, P<0.001; right: F=40.076, P<0.001). In terms of reproducibility, the MAX has significantly higher CV value (>= 18.6%) than the other methods, while the INS has the lowest CV value (<= 2.7%). On the performance of classification, the INS produces the highest AUC values (left: 0.854; right: 0.872). The MIN and D2 also have a passable performance (AUC > 0.8). The choice of timing algorithm affects baPWV values and the quality of measurement. The INS method is recommended for baPWV measurement. PMID- 24211906 TI - High cycle fatigue behavior of implant Ti-6Al-4V in air and simulated body fluid. AB - Ti-6Al-4V implants that function as artificial joints are usually subjected to long-term cyclic loading. To study long-term fatigue behaviors of implant Ti-6Al 4V in vitro and in vivo conditions exceeding 107 cycles, constant stress amplitude fatigue experiments were carried out at ultrasonic frequency (20 kHz) with two different surface conditions (ground and polished) in ambient air and in a simulated body fluid. The initiation mechanisms of fatigue cracks were investigated with scanning electron microscopy. Improvement of fatigue strength is pronounced for polished specimens below 106 cycles in ambient air since fatigue cracks are initiated from surfaces of specimens. While the cycles exceed 106, surface conditions have no effect on fatigue behaviors because the defects located within the specimens become favorable sites for crack initiation. The endurance limit at 108 cycles of polished Ti-6Al-4V specimens decreases by 7% if it is cycled in simulated body fluid instead of ambient air. Fracture surfaces show that fatigue failure is initiated from surfaces in simulated body fluid. Surface improvement has a beneficial effect on fatigue behaviors of Ti-6Al-4V at high stress amplitudes. The fatigue properties of Ti-6Al-4V deteriorate and the mean endurance limits decrease significantly in simulated body fluid. PMID- 24211907 TI - Gaussian fitting for carotid and radial artery pressure waveforms: comparison between normal subjects and heart failure patients. AB - It has been reported that Gaussian functions could accurately and reliably model both carotid and radial artery pressure waveforms (CAPW and RAPW). However, the physiological relevance of the characteristic features from the modeled Gaussian functions has been little investigated. This study thus aimed to determine characteristic features from the Gaussian functions and to make comparisons of them between normal subjects and heart failure patients. Fifty-six normal subjects and 51 patients with heart failure were studied with the CAPW and RAPW signals recorded simultaneously. The two signals were normalized first and then modeled by three positive Gaussian functions, with their peak amplitude, peak time, and half-width determined. Comparisons of these features were finally made between the two groups. Results indicated that the peak amplitude of the first Gaussian curve was significantly decreased in heart failure patients compared with normal subjects (P<0.001). Significantly increased peak amplitude of the second Gaussian curves (P<0.001) and significantly shortened peak times of the second and third Gaussian curves (both P<0.001) were also presented in heart failure patients. These results were true for both CAPW and RAPW signals, indicating the clinical significance of the Gaussian modeling, which should provide essential tools for further understanding the underlying physiological mechanisms of the artery pressure waveform. PMID- 24211909 TI - A supportive attribute-assisted discretization model for medical classification. AB - Discretization of a continuous-valued symptom (attribute) in medical data set is a crucial preprocessing step for the medical classification task. This paper proposes a supportive attribute - assisted discretization (SAAD) model for medical diagnostic problems. The intent of this approach is to discover the best supportive symptom that correlates closely with the continuous-valued symptom being discretized and to conduct the discretization process using the significant supportive information that is provided by the best supportive symptom, because we hypothesize that a good discretization scheme should rely heavily on the interaction between a continuous-valued attribute and both its supportive attribute and the class attribute. SAAD can consider each continuous-valued symptom differently and intelligently, which allows it to be capable of minimizing the information lost and the data uncertainty. Hence, SAAD results in higher classification accuracy. Empirical experiments using ten real-life datasets from the UCI repository were conducted to compare the classification accuracy achieved by several prestigious classifiers with SAAD and other state-of the-art discretization approaches. The experimental results demonstrate the effectiveness and usefulness of the proposed approach in enhancing the diagnostic accuracy. PMID- 24211908 TI - Exploration and comparison of the pre-impact lead time of active and passive falls based on inertial sensors. AB - Research on falls in elderly people has a great social significance because of the rapidly growing of the aging population. The pre-impact lead time of fall (PLT) is an important part of the human fall theory. PLT is the longest time for a person who is going to fall to take action in order to prevent the fall or to reduce bodily injuries from the fall impact. However, there is no clear definition of PLT so far. There is also no comparative study for active and passive falls. In this study, we proposed a theoretical definition of the PLT, based on a new method of fall event division. We also compared the differences of PLT and the related angles between active and passive falls. Eight healthy adult subjects were arranged to perform three kinds of activities of daily living (sitting, walking and lying), and two kinds fall activities (active and passive) in three directions (forward, backward and lateral fall). Nine inertial sensor modules were used to measure the body segmental kinematic characteristics of each subject in our experimental activities. In this paper, a fall event was suggested to divide into three or four phases and then the critical phase could be divided into three periods (pre-impact, impact, and post-impact). Two fall models were developed for active and passive falls using acceleration data. The average value of PLT for active falls is about 514 +/- 112 ms and it is smaller than the value for passive falls, which is 731 +/- 104 ms. The longest PLTs were measured on the chest or waist instead of other locations, such as the thigh and shank. The PLTs of the three kinds of fall activities were slightly different, but there was a significant difference between two fall modes. The PLT showed the correlation to the body angle at the start of PLT, but it was uncorrelated at the end of PLT. The angles at the start of PLT had slight variations (<10 degrees) from the steady standing state except in passive forward falls (max 16 degrees) due to the self-control. The landing angles were significantly different in the both fall modes in all the three directions of fall, indicating the state of the trunk was uncertain when the hip contacted the ground. It can be concluded that it is feasible to prevent falls by using an early pre-impact fall alarm device; the present study provides important reference for development of pre-impact fall alarm devices. PMID- 24211910 TI - Characteristic analysis of the lower limb muscular strength training system applied with MR dampers. AB - A new training system that can adjust training intensity and indicate the center pressure of a subject was proposed by applying controlled electric current to the Magneto-Rheological damper. The experimental studying on the muscular activities were performed in lower extremities during maintaining and moving exercises, which were processed on an unstable platform with Magneto rheological dampers and recorded in a monitor. The electromyography (EMG) signals of the eight muscles in lower extremities were recorded and analyzed in certain time and frequency domain. Muscles researched in this paper were rectus femoris (RF), biceps femoris (BF), tensor fasciae latae (TFL), vastuslateralis (VL), vastusmedialis (VM), gastrocnemius (Ga), tibialis anterior (TA), and soleus (So). Differences of muscular activities during four moving exercises were studied in our experimental results. The rate of the increment of the muscular activities was affected by the condition of the unstable platform with MR dampers, which suggested the difference of moving exercises could selectively train each muscle with varying intensities. Furthermore, these findings also proposed that this training system can improve the ability of postural balance. PMID- 24211911 TI - Adaptive clutter filter in 2-D color flow imaging based on in vivo I/Q signal. AB - Color flow imaging has been well applied in clinical diagnosis. For the high quality color flow images, clutter filter is important to separate the Doppler signals from blood and tissue. Traditional clutter filters, such as finite impulse response, infinite impulse response and regression filters, were applied, which are based on the hypothesis that the clutter signal is stationary or tissue moves slowly. However, in realistic clinic color flow imaging, the signals are non-stationary signals because of accelerated moving tissue. For most related papers, simulated RF signals are widely used without in vivo I/Q signal. Hence, in this paper, adaptive polynomial regression filter, which is down mixing with instantaneous clutter frequency, was proposed based on in vivo carotid I/Q signal in realistic color flow imaging. To get the best performance, the optimal polynomial order of polynomial regression filter and the optimal polynomial order for estimation of instantaneous clutter frequency respectively were confirmed. Finally, compared with the mean blood velocity and quality of 2-D color flow image, the experiment results show that adaptive polynomial regression filter, which is down mixing with instantaneous clutter frequency, can significantly enhance the mean blood velocity and get high quality 2-D color flow image. PMID- 24211912 TI - The temperature field simulation of radiofrequency catheter-based renal sympathetic denervation for resistant hypertension. AB - Renal sympathetic denervation (RSD) by the radiofrequency ablation was used to treat the resistant hypertension in clinic and has achieved curative effect. But the temperature distribution in the artery walls and the blood flow have not been investigated. Finite element method (FEM) based on Comsol Multiphysics 4.3a software was used to simulate the temperature distribution in the renal artery. The results of renal artery temperature distribution as well as blood flow effect on the temperature field were obtained, which demonstrated that the blood velocity is very crucial in the temperature distribution of blood vessel near antenna. When the speed of blood is 0.4 m/s, the highest temperature rise of arterial wall near the antenna is 8.882 degrees C (37 degrees C to 45.882 degrees C) and contralateral artery wall's highest temperature rise is about 5 degrees C (37 degrees C to 42 degrees C). This temperature value can damage renal sympathetic nerves to cure the resistant hypertension. Due to the blood flow, the temperature field stretches to the direction of blood flow. The temperature rise of blood is only in a small range (37 degrees C to 41 degrees C) at both ends of the antenna. The simulation of RSD by the radiofrequency ablation can give doctors a better scheme to avoid the vascular injury in different blood flow rates and radiofrequency voltages. PMID- 24211913 TI - Hemodynamic parameters measurements to assess severity of serial lesions in patient specific right coronary artery. AB - In this study, effects of serial stenosis on coronary hemodynamics were investigated in the human right coronary artery (RCA) using blood flow analysis. A 3-D model of a serial stenosed RCA was reconstructed based on multislice computerized tomography images. Numerical analysis examined the effect of multiple serial stenoses on the hemodynamic characteristics such as flow separation, pressure drop and FFR. Pressure loss associated with flow expansion after each constriction was large. Overall pressure drop increased from 1700 Pa (12.75 mmHg) at the end diastole to 11000 Pa (82.5 mmHg) at the peak systole. In two stenoses the corresponding pressure gradients werearound 30 mmHg and corresponded to the stenosis with FFR < 0.7 (associated to the sever stenosis). Severe stenosies caused large pressure drops across the throat. Blood flow distal to the stenosis was associated with fluctuations of the wall shear stress and vorticity. PMID- 24211914 TI - Automatic lung fields segmentation in CT scans using morphological operation and anatomical information. AB - Segmenting lung fields from CT (Computed Tomography) scans is an important task for the analysis, diagnosis and treatment of pulmonary diseases. Although many segmentation methods have been presented, some new automatic segmentation methods for the lung fields are still proposed for the CT scans. This paper proposes a novel segmentation method for lung fields by using morphological closing operations and thresholding for normal lungs in CT scans. Additionally, under the guidance of anatomic information, the lung fields could be well segmented with lobar fissure, thin junction between the left/right lung fields, indentation of the blood vessels and bronchi-walls. This experiment is performed by employing the thoracic CT scans datasets, and it is proved to be an effective method. PMID- 24211915 TI - A novel finite element-based patient-specific mitral valve repair: virtual ring annuloplasty. AB - Alterations of normal mitral valve (MV) function lead to mitral insufficiency, i.e., mitral regurgitation (MR). Mitral repair is the most popular and most efficient surgical intervention for MR treatment. An annuloplasty ring is implanted following complex reconstructive MV repairs to prevent potential reoccurrence of MR. We have developed a novel finite element (FE)-based simulation protocol to perform patient-specific virtual ring annuloplasty following the standard clinical guideline procedure. A virtual MV was created using 3D echocardiographic data in a patient with mitral annular dilation. Proper type and size of the ring were determined in consideration of the MV apparatus geometry. The ring was positioned over the patient MV model and annuloplasty was simulated. Dynamic simulation of MV function across the complete cardiac cycle was performed. Virtual patient-specific annuloplasty simulation well demonstrated morphologic information of the MV apparatus before and after ring implantation. Dynamic simulation of MV function following ring annuloplasty demonstrated markedly reduced stress distribution across the MV leaflets and annulus as well as restored leaflet coaptation compared to pre-annuloplasty. This novel FE-based patient-specific MV repair simulation technique provides quantitative information of functional improvement following ring annuloplasty. Virtual MV repair strategy may effectively evaluate and predict interventional treatment for MV pathology. PMID- 24211916 TI - Visual attention recognition based on nonlinear dynamical parameters of EEG. AB - Varieties of neurophysiological measures have been utilized in visual attention studies. The linear parameters like power spectrum are the most commonly used features in the existing studies. In this paper, however, nonlinear parameters including approximate entropy, sample entropy and multiscale entropy were tested. All subjects were instructed to perform tasks with three different attention levels (i.e. attention, no attention and rest) in two experiments. Nonlinear features were extracted from the EEG signals. Then, statistical analyses and classification with support vector machine (SVM) were performed. A comparison between the classification results based on the linear feature / and the sample entropy was performed for further analysis. The results suggest that sample entropy stands out in the dynamical parameters with the accuracies of 76.19% and 85.24% in recognition of three levels of attention for the two experiments respectively. And the further comparison shows that the sample entropy performs even better than the / power ratio. It is suggested that nonlinear dynamical parameters may be indispensable for a robust attention recognition system. PMID- 24211917 TI - A novel classification method based on ICA and ELM: a case study in lie detection. AB - The classification of EEG tasks has drawn much attention in recent years. In this paper, a novel classification model based on independent component analysis (ICA) and Extreme learning machine (ELM) is proposed to detect lying. Firstly, ICA and its topography information were used to automatically identify the P300 ICs. Then, time and frequency-domain features were extracted from the reconstructed P3 waveforms. Finally, two classes of feature samples were used to train ELM, Back propagation network (BPNN) and support vector machine (SVM) classifiers for comparison. The optimal number of P3 ICs and the values of classifier parameter were optimized by the cross-validation procedures. Experimental results show that the presented method (ICA_ELM) achieves the highest training accuracy of 95.40% with extremely less training and testing time on detecting P3 components for the guilty and the innocent subjects. The results indicate that the proposed method can be applied in lie detection. PMID- 24211918 TI - ECG baseline wander correction based on mean-median filter and empirical mode decomposition. AB - A novel approach of ECG baseline wander correction based on mean-median filter and empirical mode decomposition is presented in this paper. The low frequency parts of the original signals were removed by the mean median filter in a nonlinear way to obtain the baseline wander estimation, then its series of IMFs were sifted by t-test after empirical mode decomposition. The proposed method, tested by the ECG signals in MIT-BIH Arrhythmia database and European ST_T database, is more effective compared with other baseline wander removal methods. PMID- 24211919 TI - Validation of an improved 'diffeomorphic demons' algorithm for deformable image registration in image-guided radiation therapy. AB - Deformable image registration (DIR) was widely used in radiation therapy, such as in automatic contour generation, dose accumulation, tumor growth or regression analysis. To achieve higher registration accuracy and faster convergence, an improved 'diffeomorphic demons' registration algorithm was proposed and validated. Based on Brox et al.'s gradient constancy assumption and Malis's efficient second-order minimization (ESM) algorithm, a grey value gradient similarity term and a transformation error term were added into the demons energy function, and a formula was derived to calculate the update of transformation field. The limited Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm was used to optimize the energy function so that the iteration number could be determined automatically. The proposed algorithm was validated using mathematically deformed images and physically deformed phantom images. Compared with the original 'diffeomorphic demons' algorithm, the registration method proposed achieve a higher precision and a faster convergence speed. Due to the influence of different scanning conditions in fractionated radiation, the density range of the treatment image and the planning image may be different. In such a case, the improved demons algorithm can achieve faster and more accurate radiotherapy. PMID- 24211920 TI - The effect of counter-ions on the ion selectivity of potassium and sodium ions in nanopores. AB - The ion selective transport plays an important role in the function of cell membranes, and promotes the application of artificial permeable membranes. This phenomenon has been studied in case for different diameters and functional groups of nanopores. In this work, we focus on the effect of anions on cation selectivity, in particular the influence of various halide ions on K+ and Na+ selectivity. We adopted molecular dynamics simulations with non-charged nanopores under constant temperature and uniform concentration. The results show K+ selectivity in the solution with Cl- and Na+-selectivity in the solution with Br- and I-. This selectivity, on the contrary, disappears in the solution with F-. We also investigate the change of the hydration shell of ions and cation-anion interactions between in the bulk region and in the nanopores, which could explain this selective phenomenon. PMID- 24211921 TI - Toward continuous ambulatory monitoring using a wearable and wireless ECG- recording system: a study on the effects of signal quality on arrhythmia detection. AB - Five well-known arrhythmia classification algorithms were compared in this paper based on the recommendations in AAMI standard. They are C4.5, k-Nearest Neighbor, Multilayer Perceptron, PART, and Support Vector Machine, respectively, with inputs related to heartbeat intervals and ECG morphological features. They were evaluated on three independent datasets, including the MIT-BIH arrhythmia database, a collection of ECG signals acquired from healthy subjects by the wireless Body Sensor Network (BSN) nodes, and a third dataset captured also by the BSN nodes. Results showed the overall accuracy on the MIT-BIH arrhythmia database was approximately 99.04%, with high sensitivity, specificity, and selectivity. When tested with ECG signals acquired from the human subjects, which were partially deteriorated due to several factors, e.g., motion artifacts and data transmission problems, the overall accuracy of 94.19% and that of 81.22% were obtained for static activities and dynamic activities, respectively. In addition, the effects of the signal quality from these human subjects on false alarms were investigated. When false alarms occurring in signal segments with low quality were excluded, the number of false detections reduced from 14.17% to 8.65%. When evaluated on signals generated by the patient simulator, which included several types of premature ventricular contraction without artifacts from body movements, a high classification accuracy was also observed. PMID- 24211922 TI - Measurement of stapes vibration in Human temporal bones by round window stimulation using a 3-coil transducer. AB - Round window placement of a 3-coil transducer offers a new approach for coupling an implantable hearing aid to the inner ear. The transducer exhibits high performance at low-frequencies. One remarkable feature of the 3-coil transducer is that it minimizes leakage flux. Thus, the transducer, which consists of two permanent magnets and three coils, can enhance vibrational displacement. In human temporal bones, stapes vibration was observed by laser Doppler vibrometer in response to round window stimulation using the 3-coil transducer. Coupling between the 3-coil transducer and the round window was connected by a wire-rod. The stimulation created stapes velocity when the round window stimulated. Performance evaluation was conducted by measuring stapes velocity. To verify the performance of the 3-coil transducer, stapes velocity for round window and tympanic membrane stimulation were compared, respectively. Stapes velocity by round window stimulation using the 3-coil transducer was approximately 14 dB higher than that achieved by tympanic membrane stimulation. The study shows that 3-coil transducer is suitable for implantable hearing aids. PMID- 24211923 TI - Improved bioavailability and antiasthmatic efficacy of poorly soluble curcumin solid dispersion granules obtained using fluid bed granulation. AB - The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin 13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR. PMID- 24211924 TI - In-line phase contrast micro-CT reconstruction for biomedical specimens. AB - X-ray phase contrast micro computed tomography (micro-CT) can non-destructively provide the internal structure information of soft tissues and low atomic number materials. It has become an invaluable analysis tool for biomedical specimens. Here an in-line phase contrast micro-CT reconstruction technique is reported, which consists of a projection extraction method and the conventional filter back projection (FBP) reconstruction algorithm. The projection extraction is implemented by applying the Fourier transform to the forward projections of in line phase contrast micro-CT. This work comprises a numerical study of the method and its experimental verification using a biomedical specimen dataset measured at an X-ray tube source micro-CT setup. The numerical and experimental results demonstrate that the presented technique can improve the imaging contrast of biomedical specimens. It will be of interest for a wide range of in-line phase contrast micro-CT applications in medicine and biology. PMID- 24211925 TI - In vivo evaluation of mastication noise reduction for dual channel implantable microphone. AB - Input for fully implantable hearing devices (FIHDs) is provided by an implantable microphone under the skin of the temporal bone. However, the implanted microphone can be affected when the FIHDs user chews. In this paper, a dual implantable microphone was designed that can filter out the noise from mastication. For the in vivo experiment, a fabricated microphone was implanted in a rabbit. Pure-tone sounds of 1 kHz through a standard speaker were applied to the rabbit, which was given food simultaneously. To evaluate noise reduction, the measured signals were processed using a MATLAB program based adaptive filter. To verify the proposed method, the correlation coefficients and signal to-noise ratio before and after signal processing were calculated. By comparing the results, signal-to-noise ratio and correlation coefficients are enhanced by 6.07dB and 0.529 respectively. PMID- 24211926 TI - Mucoadhesive polymer films for tissue retraction in laparoscopic surgery: Ex-vivo study on their mechanical properties. AB - Safe and effective manipulation of soft tissue during laparoscopic procedures can be achieved by the use of mucoadhesive polymer films. A series of novel adhesive polymer films were formulated in house based on either Carbopol or Chitosan modified systems. The mechanical properties of the polymers and their adherence to bowel were evaluated using ex-vivo pig bowel immersed in 37 degrees C water bath and connected to an Instron tensiometer. Young's modulus was 300 kPa for the Carbopol-polymer and 5 kPa for the Chitosan-polymer. The Chitosan-polymer exhibited much larger shear adhesion than its tensile adhesion: 3.4 N vs. 1.2. Both tensile and shear adhesions contributed to the large retraction force (2.6 N) obtained during l polymer-bowel retraction testing. Work of adhesion at the polymer/serosa interface, defined as the area under the force curve, was 64 mJ, which is appreciably larger than that reported with existing polymers. In conclusion, adhesive polymers can stick to the serosal side of the bowel with an adhesive force, which is sufficient to lift the bowel, providing a lower retraction stress than that caused by laparoscopic grasping which induces high localized pressures on the tissue. PMID- 24211927 TI - Inter-tester and intra-tester reliability of ultrasound imaging measurements of abdominal muscles in adolescents with and without idiopathic scoliosis: a case controlled study. AB - The present study established inter-tester and intra-tester reliabilities of ultrasound imaging and diagnostically differentiated muscle imbalances in lateral abdominal muscle sizes between normal adolescents and adolescents with idiopathic scoliosis (AIS). Fifteen adolescents with AIS were age- and gender-matched with 15 normal adolescents. There was no significant difference between bilateral abdominal muscles in normal adolescents, but there was a significant difference between bilateral abdominal muscles in adolescents with AIS (P<0.05). Overall, inter-tester and intra-tester reliabilities in normal and AIS adolescents ranged from 0.801-0.984. This novel study shows that using ultrasound imaging to measure lateral abdominal muscle thickness is: (1) highly reliable between and within the testers; and (2) capable of distinguishing between subjects with and without pathological muscle morphology due to AIS. PMID- 24211928 TI - Hemodynamic numerical simulation and analysis of oscillatory blood flow in growing aneurysms. AB - Hemodynamics plays a crucial role in the formation, progression and rupture of intracranial aneurysms. Understanding these mechanisms is important to improve current diagnosis and treatment of intracranial aneurysms. In this study we simulate and analyze the pressure gradients and the blood flow fields in growing intracranial aneurysms. Firstly, the pressure gradients are obtained according to the blood velocity waveform at the axis of the inlet to the artery, which can be acquired by transcranial Doppler technology. Then, blood flow fields are calculated by solving the linearized Navier-Stokes equations and continuity equation using the Fourier series method. Results show that the higher the aneurysm dilatation degree is, the lower the maximum oscillatory velocity will be. Therefore, the oscillatory velocity may be used to analyze the characteristics of blood flow signals from aneurysm and to forecast the size of aneurysm. This sensitive parameter can be utilized for the detection of vessel diseases, which is promising to provide a useful reference in clinical application. PMID- 24211929 TI - Shear wave speed estimation by adaptive random sample consensus method. AB - This paper describes a new method for shear wave velocity estimation that is capable of extruding outliers automatically without preset threshold. The proposed method is an adaptive random sample consensus (ARANDSAC) and the metric used here is finding the certain percentage of inliers according to the closest distance criterion. To evaluate the method, the simulation and phantom experiment results were compared using linear regression with all points (LRWAP) and radon sum transform (RS) method. The assessment reveals that the relative biases of mean estimation are 20.00%, 4.67% and 5.33% for LRWAP, ARANDSAC and RS respectively for simulation, 23.53%, 4.08% and 1.08% for phantom experiment. The results suggested that the proposed ARANDSAC algorithm is accurate in shear wave speed estimation. PMID- 24211930 TI - IB-LBM simulation on blood cell sorting with a micro-fence structure. AB - A size-based blood cell sorting model with a micro-fence structure is proposed in the frame of immersed boundary and lattice Boltzmann method (IB-LBM). The fluid dynamics is obtained by solving the discrete lattice Boltzmann equation, and the cells motion and deformation are handled by the immersed boundary method. A micro fence consists of two parallel slope post rows which are adopted to separate red blood cells (RBCs) from white blood cells (WBCs), in which the cells to be separated are transported one after another by the flow into the passageway between the two post rows. Effected by the cross flow, RBCs are schemed to get through the pores of the nether post row since they are smaller and more deformable compared with WBCs. WBCs are required to move along the nether post row till they get out the micro-fence. Simulation results indicate that for a fix width of pores, the slope angle of the post row plays an important role in cell sorting. The cells mixture can not be separated properly in a small slope angle, while obvious blockages by WBCs will take place to disturb the continuous cell sorting in a big slope angle. As an optimal result, an adaptive slope angle is found to sort RBCs form WBCs correctly and continuously. PMID- 24211931 TI - Nonlinear dynamic characteristics of SMA intravascular stent under radial stochastic loads. AB - Nonlinear dynamic characteristics of shape memory alloy (SMA) intravascular stent under radial stochastic loads were studied in this paper. Von de Pol item was improved to interpret the hysteretic phenomena of SMA, and the nonlinear dynamic model of SMA intravascular stent under radial stochastic loads was developed. The conditions of stochastic stability of the system were obtained in singular boundary theory. The steady-state probability density function of the dynamic response of the system was given, and the stochastic Hopf bifurcation characteristics of the system were analyzed. Theoretical analysis and numerical simulation show that the stability of the trivial solution varies with bifurcation parameters, and stochastic Hopf bifurcation appears in the process, which can cause stent fracture or loss. The results of this paper are helpful to application of SMA intravascular stent in biomedical engineering fields. PMID- 24211932 TI - Modeling the circle of Willis to assess the effect of anatomical variations on the development of unilateral internal carotid artery stenosis. AB - Circle of Willis (CoW) plays a significant role in maintaining the blood supply for the brain. Specifically, when the stenosis occurs in the internal carotid artery (ICA), abnormal structures of CoW would decrease the compensatory capacity, leading to the local insufficiency of cerebral blood supply. The present paper built a series of lumped parameter models for CoW, and simulated the blood redistribution caused by the unilateral ICA stenosis with different severities in cerebral arteries in the normal and abnormal CoW respectively. The results showed that when unilateral ICA stenosis occurred, the collateral circulation was built through the anterior communicating artery and the ipsilateral posterior communicating artery, maintaining the flow in cerebral arteries. The absence of the two communicating arteries would cause an obvious decrease of flow in local cerebral arteries in the anterior circulation. In conclusion, the two arteries play a significant role in maintaining the balance of cerebral blood supply in the development of ICA stenosis. PMID- 24211933 TI - A removable hybrid robot system for long bone fracture reduction. AB - In traditional long bone fracture reduction surgery, there are some drawbacks such as low accuracy, high radiation for surgeons and a risk of infection. To overcome these disadvantages, a removable hybrid robot system is developed, which integrates a removable series-parallel mechanism with a motor-double cylinder (MDC) driven mode. This paper describes the mechanism in detail, analyses the principle and the method of the fracture reduction, presents the surgical procedure, and verifies the reduction accuracy by experiments with bone models. The results are shown as follows. The mean deviations of the axial displacement and lateral displacement are 1.60mm and 1.26 mm respectively. The standard deviations are 0.69 mm and 0.30 mm. The mean deviations of the side angle and turn inward are 2.06 degrees and 2.22 degrees respectively. The standard deviations are 0.50 degrees and 0.99 degrees . This minimally invasive robot features high accuracy and zero radiation for surgeons, and is able to conduct fracture reduction for long bones. PMID- 24211934 TI - Projective invariant biplanar registration of a compact modular orthopaedic robot. AB - This paper presents a compact orthopedic robot designed with modular concept. The layout of the modular configuration is adaptive to various conditions such as surgical workspace and targeting path. A biplanar algorithm is adopted for the mapping from the fluoroscopic image to the robot, while the former affine based method is satisfactory only when the projection rays are basically perpendicular to the reference coordinate planes. This paper introduces the area cross-ratio as a projective invariant to improve the registration accuracy for non-orthogonal orientations, so that the robotic system could be applied to more orthopedic procedures under various C-Arm orientation conditions. The system configurations for femoral neck screw and sacroiliac screw fixation are presented. The accuracy of the robotic system and its efficacy for the two typical applications are validated by experiments. PMID- 24211935 TI - A smart capsule system of gastric occult blood detection. AB - Prior research indicated that occult blood screening can be used to detect early gastric cancer. Based on capsule endoscopy and occult blood detection theory, an automatic detection capsule system for gastric occult blood (GOB) was proposed. This paper designed the detecting sensor, image acquisition system and wireless transmitter module respectively based on collaurum immune theory, the image sensor and radio frequency chip. In vitro experiments were conducted to testify the system, and the detecting result image information was acquired by the image acquisition (IMAQ) system and transmitted to the outside of the body through the wireless transmitter module. The receiver module received and displayed the information on the computer, from which doctors could diagnose whether there was occult blood (OB) or not. Therefore, this paper provides a new idea for the screening of early-stage gastric cancer with reliability and simplicity. PMID- 24211936 TI - A 3D undulatory locomotion system inspired by nematode C. elegans. AB - This paper provides an undulatory locomotion model inspired by C. elegans, whose nervous system and muscular structure are well studied. C. elegans is divided into 11 muscle segments according to its anatomical structure, and represented as a multi-joint rigid link model in this work. In each muscle segment, there are four pieces of muscles located in four quadrants. The muscles change their lengths according to the outputs of nervous system. In this work, the dynamic neural networks (DNN) are adopted to represent the nervous system. The DNN are divided into the head DNN and the body DNN. The head DNN produces the sinusoid waves to generate the forward and backward undulatory movements. The body DNN with 11 segments is responsible for passing the sinusoid wave and creating the phase lag. The 3D locomotion of this system are implemented by using the DNN to control the muscle lengths, and then using the muscle lengths to control the angles between two consecutive links on both horizontal and vertical planes. The test results show good performances of this model in both forward and backward locomotion in 3D, which could serve as a prototype of the micro-robot for clinical use. PMID- 24211937 TI - Fuzzy speed function based active contour model for segmentation of pulmonary nodules. AB - Pulmonary nodules are potential manifestation of lung cancer. Accurate segmentation of juxta-vascular nodules and ground glass opacity (GGO) nodules is an important and active area of research in medical image processing. At present, the classical active contour models (ACM) for segmentation of pulmonary nodules may cause the problem of boundary leakage. In order to solve the problem, a new fuzzy speed function-based active model for segmentation of pulmonary nodules is proposed in this paper. The fuzzy speed function incorporated into the ACM is calculated by the degree of membership based on intensity feature and local shape index. At the boundary of pulmonary nodules, the fuzzy speed function approaches zero and the evolution of the contour curve will stop, so the accurate segmentation of pulmonary nodules can be obtained. Experimental results on juxta vascular nodules and GGO nodules show that the proposed ACM can achieve accurate segmentation. PMID- 24211938 TI - Design and optimization of multi-class series-parallel linear electromagnetic array artificial muscle. AB - Skeletal muscle exhibiting complex and excellent precision has evolved for millions of years. Skeletal muscle has better performance and simpler structure compared with existing driving modes. Artificial muscle may be designed by analyzing and imitating properties and structure of skeletal muscle based on bionics, which has been focused on by bionic researchers, and a structure mode of linear electromagnetic array artificial muscle has been designed in this paper. Half sarcomere is the minimum unit of artificial muscle and electromagnetic model has been built. The structural parameters of artificial half sarcomere actuator were optimized to achieve better movement performance. Experimental results show that artificial half sarcomere actuator possesses great motion performance such as high response speed, great acceleration, small weight and size, robustness, etc., which presents a promising application prospect of artificial half sarcomere actuator. PMID- 24211939 TI - Modeling bistable behaviors in morphing structures through finite element simulations. AB - Bistable structures, exemplified by the Venus flytrap and slap bracelets, can transit between different configurations upon certain external stimulation. Here we study, through three-dimensional finite element simulations, the bistable behaviors in elastic plates in the absence of terminate loads, but with pre strains in one (or both) of the two composite layers. Both the scenarios with and without a given geometric mis-orientation angle are investigated, the results of which are consistent with recent theoretical and experimental studies. This work can open ample venues for programmable designs of plant/shell structures with large deformations, with applications in designing bio-inspired robotics for biomedical research and morphing/deployable structures in aerospace engineering. PMID- 24211940 TI - Mechanical strength of sutured block copolymers films for load bearing medical applications. AB - The mechanical behavior of three styrenic thermoplastic block copolymer elastomers with applied surgical sutures was studied by uniaxial tensile testing. The materials exhibited oriented cylindrical microstructure. Distinct macroscopic deformation mechanisms have been observed upon stretching of samples with vertical and horizontal orientation. Deformation progressed along the axis of the suture in samples with parallel orientation (P), while it in case of normal orientation (N) the whole sample responded to the applied force. Also the analysis of the stress-strain curves showed a significant difference between samples P and N. Greater stress at break was observed for samples P, while samples N showed the capability to tolerate higher strain. The influence of morphology on the tear-out shape has been also observed. The thread made a vertical tear out in samples P while for samples N ripping off the bottom was observed. PMID- 24211941 TI - Enhanced oral bioavailability and controlled release of dutasteride by a novel dry elixir. AB - To develop a solid dosage form of dutasteride for improving its oral bioavailability, a novel dry elixir (DE) system was fabricated. DEs incorporating dextrin and/or xanthan gum were prepared using spray-drying and evaluated by morphology, ethanol content, crystallinity, dissolution and oral bioavailability. DEs were spherical with a smooth surface and had an average particle size of 20 25 MUm. The ethanol content could be easily varied by controlling the spray drying temperature. The dissolution profiles of dutasteride from each DE proved to be much faster than that of dutasteride powder due to the amorphous state and a high amount of incorporated ethanol. In particular, the pharmacokinetic profiles of dutasteride were significantly altered depending on the proportions of dextrin and xanthan gum. Blood concentrations of dutasteride from DE formulations were similar to those of market products and much greater than those of native dutasteride. Interestingly, the dissolution and pharmacokinetic profiles were easily controlled by changing the ratio of dextrin to xanthan gum. The data suggests that a DE using dextrin and/or xanthan gum could provide an applicable solid dosage form to improve the dissolution and bio-availability of dutasteride as well as to modulate its pharmacokinetics. PMID- 24211942 TI - Hybrid diffusive/PVD treatments to improve the tribological resistance of Ti-6Al 4V. AB - Titanium alloys are nowadays used for a wide range of biomedical applications thanks to their combination of high mechanical resistance, high corrosion resistance and biocompatibility. Nevertheless, the applicability of titanium alloys is sometimes limited due to their low microhardness and tribological resistance. Thus the titanium alloys cannot be successfully applied to prosthetic joint couplings. A wide range of surface treatments, in particular PVD coatings such as CrN and TiN, have been used in order to improve the tribological behaviour of titanium alloys. However, the low microhardness of the titanium substrate often results in coating failure due to cracks and delamination. For this reason, hybrid technologies based on diffusive treatments and subsequent PVD coatings may improve the overall coating resistance. In this work, conventional PVD coatings of CrN or TiCN, deposited on Titanium Grade 5, were characterized and then combined with a standard thermal diffusive nitriding treatment in order to improve the tribological resistance of the titanium alloys and avoid coating delamination. The different treatments were studied by means of scanning electron microscopy both on the sample surface and in cross-section. In-depth composition profiles were obtained using glow discharge optical emission spectrometry (GDOES) and localized energy dispersive X-ray diffraction on linear scan-lines. The microhardness and adhesion properties of the different treatments were evaluated using Vickers microhardness tests at different load conditions. The indentations were observed by means of SEM in order to evaluate delaminated areas and the crack's shape and density. The tribological behaviour of the different treatments was tested in dry conditions and in solution, in alternate pin-on-flat configuration, with a frequency of 0.5 Hz. After testing, the surface was investigated by means of stylus profilometry and SEM both on the surface and in cross-section. The standalone PVD coatings show a limited tribological resistance due to the low hardness of the substrate, which results in fractures and delamination. The combination of a diffusive process and a subsequent PVD coating shows a stronger effect in improving the tribological resistance of the substrate. PMID- 24211943 TI - A novel spinal kinematic analysis using X-ray imaging and vicon motion analysis: a case study. AB - This study highlights a novel spinal kinematic analysis method and the feasibility of X-ray imaging measurements to accurately assess thoracic spine motion. The advanced X-ray Nash-Moe method and analysis were used to compute the segmental range of motion in thoracic vertebra pedicles in vivo. This Nash-Moe X ray imaging method was compared with a standardized method using the Vicon 3 dimensional motion capture system. Linear regression analysis showed an excellent and significant correlation between the two methods (R2 = 0.99, p < 0.05), suggesting that the analysis of spinal segmental range of motion using X-ray imaging measurements was accurate and comparable to the conventional 3 dimensional motion analysis system. Clinically, this novel finding is compelling evidence demonstrating that measurements with X-ray imaging are useful to accurately decipher pathological spinal alignment and movement impairments in idiopathic scoliosis (IS). PMID- 24211944 TI - Preparation of DOX/BSANP and its antitumor effect on bel-7404 liver cancer cells in vitro and in vivo. AB - This paper aimed to investigate the preparation of doxorubicin-loaded bovine serum albumin nanoparticles (DOX/BSANP) and their effect on killing liver cancer cells in vitro and in vivo. DOX/BSANP was prepared using a desolvation-chemical crosslinking method. Their morphology and particle size were observed using transmission electron microscopy (TEM). The envelopment, drug-loading rates and slow-release characteristics were determined spectrophotometrically. Their ability to kill liver cancer cells in vitro was determined using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry (FCM). The tumor-suppressing effect of the nanoparticles in experimental animals in vivo was also evaluated. Under TEM, DOX/BSANP appeared spherical and was distributed uniformly, with a diameter of about 120 nm and hydrated particle size of 170 nm determined by dynamic light diffraction. The envelopment rate was 82% and the drug-loading rate was 11.2%. The in vitro drug-release experiment showed that about 50% of the drug in drug-loaded nanoparticles was released continuously and slowly for 7 days. The MTT assay showed that DOX/BSANP significantly inhibited cell proliferation, while FCM showed that it induced tumor cell apoptosis. The in vivo tumor suppression test showed that the therapeutic effect of drug-loaded nanoparticles was superior to that of DOX alone. PMID- 24211945 TI - Uncertainity analysis of selected sources of errors in bioelectromagnetic investigations. AB - The aim of this paper is to focus attention of experimenters on several sources of error that are not taken into account in the majority of bioelectromagnetics experiments, and which may lead to complete falsification of the results of the experiments. PMID- 24211946 TI - Synthesis and characterization of poly(1,2-propanediol-co-1,8-octanediol-co citrate) biodegradable elastomers for tissue engineering. AB - In this paper, citric acid, 1,8-octanediol and 1,2-propanediol were used as reactive monomers to synthesize poly(1,2-propanediol-co-1,8-octanediol-co citrate) (PPOC) elastomers by melt polycondensation. The PPOC elastomers were characterized by FTIR, 1H-NMR, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), hydrophilic test and mechanical test. The results indicated that citric acid had reacted with 1,8-octanediol and 1,2-propanediol, respectively. The sol content, swelling degree and hydrophilicity of PPOC elastomers increased with the higher content of 1,2-propanediol, while the tensile strength and the thermal degradation temperature decreased. The results indicate the addition of 1,2-propanediol reduces the crosslinking density and the flexibility of PPOC elastomers. PMID- 24211947 TI - Numerical simulation research to both the external fixation surgery scheme of intertrochanteric fracture and the healing process, and its clinical application. AB - In this paper, the single arm external fixation of intertrochanteric fracture healing process after surgery was simulated to obtain a postoperative fracture healing and stress distribution in the external fixator. Firstly CT images of intertrochanteric fracture are reconstructed into the femur solid model. Then based, the external fixator is installed on the model, which lastly formed a finite element model of unilateral external fixation for intertrochanteric fracture. The calculated results show: during the beginning of the fracture healing, there is much higher stress in both screws and femur in the model with solid screws than that in the model with hollow screw. The stress of the femur in the model with hollow screw is more evenly. During the middle time of Fracture healing, stress in the femoral head significantly decreases. And the stress at fracture site gradually increased with the healing occurrence. According to the results, the authors designed hollow screws to use external fixation surgery. Surgery confirmed that the use of hollow screws in fractures treatment can satisfy the strength requirements, and can effectively reduce operative time, less patient suffering. The research for external fixation can provide a reference, and promote the use of external fixation hollow screws. PMID- 24211948 TI - Fabrication of photo-crosslinked chitosan- gelatin scaffold in sodium alginate hydrogel for chondrocyte culture. AB - Photo-crosslinked chitosan-gelatin scaffolds were fabricated and applied for chondrocyte culture in vitro. Photocurable methacryloyl chitosan was synthesized and characterized by FTIR and 1H NMR, respectively. Microstructure and mechanical properties of the chitosan-gelatin scaffold treated with or without EDC as crosslinking agent were analyzed by scanning electronic microscopy (SEM), compression and viscoelastic measurement. It is demonstrated that EDC-treated chitosan-gelatin scaffold possesses better porous structure and improved mechanical properties. Photo-crosslinked chitosan-gelatin scaffold could be further integrated in sodium alginate hydrogel using calcium chloride to support proliferation of chondrocytes for over 21 days and maintain spherical phenotype, as evaluated by AlamarBlue assay and SEM, respectively, implying that the chitosan-gelatin-hydrogel system exhibits great cyto-biocompatibility. Results of this study show that photo-crosslinked chitosan-gelatin scaffold in sodium alginate hydrogel is suited as a scaffold candidate for cartilage tissue engineering. PMID- 24211949 TI - Effect of Nd:YAG laser-nitriding-treated titanium nitride surface over Ti6Al4V substrate on the activity of MC3T3-E1 cells. AB - Ti6Al4V discs with a thickness of 2.5 mm and dimensions of 15 * 15 mm2 were fabricated. The titanium nitride (TiN) surface was formed via Nd:YAG laser nitriding. A sandblast acid-etched (SA) surface was used as a control. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and surface roughness tests were conducted to study the surface and cross-section morphologies as well as the properties of TiN and SA surfaces. MC3T3-E1 osteoblast-like cells were cultured on the TiN and SA surfaces to evaluate the effect of TiN surface on cellular behaviors, including attachment, proliferation and differentiation. Morphological testing results revealed that the cross section of TiN exhibited dendritic crystallization without cracking. The proliferation and differentiation of MC3T3-E1 cells on the laser-nitriding TiN surface were significantly increased compared to those cultured on SA surface. These findings suggested that the TiN surface generated from Nd:YAG laser nitriding were favorable for the proliferation and differentiation of MC3T3-E1 cells, which is significant for implant surface modification. PMID- 24211950 TI - Computational and experimental determinations of the UV adsorption of polyvinylsilsesquioxane-silica and titanium dioxide hybrids. AB - Sunscreens that absorb UV light without photodegradation could reduce skin cancer. Polyvinyl silsesquioxanes are known to have greater thermal and photochemical stability than organic compounds, such as those in sunscreens. This paper evaluates the UV transparency of vinyl silsesquioxanes (VS) and its hybrids with SiO2(VSTE) and TiO2(VSTT) experimentally and computationally. Based on films of VS prepared by sol-gel polymerization, using benzoyl peroxide as an initiator, vinyltrimethoxysilane (VMS) formulated oligomer through thermal curing. Similarly, VSTE films were prepared from VMS and 5-25 wt-% tetraethoxysilane (TEOS) and VSTT films were prepared from VMS and 5-25 wt-% titanium tetrabutoxide (TTB). Experimental average transparencies of the modified films were found to be about 9-14% between 280-320 nm, 67-73% between 320-350nm, and 86-89% between 350 400nm. Computation of the band gap was absorption edges for the hybrids in excellent agreement with experimental data. VS, VSTE and VSTT showed good absorption in UV-C and UV-B range, but absorbed virtually no UV-A. Addition of SiO2 or TiO2 does not improve UV-B absorption, but on the opposite increases transparency of thin films to UV. This increase was validated with molecular simulations. Results show computational design can predict better sunscreens and reduce the effort of creating sunscreens that are capable of absorbing more UV-B and UV-A. PMID- 24211951 TI - Cytompatibility assessment of the surface of titanium after phosphorylation. AB - In this study, orthophosphoric acid (H3PO4) in the treatment of porous titanium (Ti) is investigated and the ability of rat bone marrow stromal cells (BMSCs) is assessed to proliferate and differentiate on these modified surfaces in vitro. To improve the cytocompatibility of Ti surfaces, pure Ti was activated commercially by simple chemical pretreatment in H3PO4 with different densities. Next, the phosphorylated specimens were soaked in simulated body fluid (SBF) to study the effect of biomineralization. The3-[4,5-dimethylthiazol-2-y1]-2, 5 diphenytetrazolium bromide (MTT) assay and the measurement of alkaline phosphatase (ALP) activity utilized to assess proliferation and differentiation of BMSCs on exposure to modified Ti surfaces. Scanning electron microscopic (SEM) images showed that the surfaces of the pre-treated samples were characterized by a complex structure which consisted of a mesh-like morphological matrix and an uniform surface with different morphic crystals of titanium dihydrogen orthophosphate (Ti(H2PO4)3). These crystals contained hydroxyl with phosphate residues that resulted in biomineralization of cells. Therefore, BMSCs reveales a well-dispersed morphology on these modified and functionalized Ti surfaces. The viability and ALP activity of BMSCs on these altered biomimetic surfaces are found to be greater than those of the controls. It is concluded that the treatment of Ti by acid etching in orthophosphoric acid is a suitable method to enhance the in vitro proliferation and differentiation of BMSCs. PMID- 24211952 TI - Dextranation of bioreducible cationic polyamide for systemic gene delivery. AB - A dextranated, bioreducible cationic polyamide was designed and employed for non viral gene delivery in vitro and in vivo. Initially, a new bioreducible cationic polyamide with p-nitrophenyl ester terminal group (denoted as SSBAP) was synthesized by polycondensation reaction of an excess amount of bis-(p nitrophenyl)-3, 3'-dithiodipropanoate and 1, 4-bis(3-aminopropyl)piperazine. The SSBAP was then chemically conjugated with 5 kDa amino-terminated dextran to yield dextran-SSBPA-dextran triblock copolymer (denoted as Dex-SSBAP-Dex). This copolymer was capable of binding genes to form nanoscale polyplexes with a near neutral surface charge. Moreover, a sufficient gene release from the polyplexes in response to an intracellular reducing environment was observed. In vitro transfection against MCF-7 and SKOV-3 cells showed that Dex-SSBAP-Dex copolymer effectively transfected the cells with comparable efficiency to that of 2 5kDa branched or linear polyethylenimine as positive controls. Besides, intravenous administration of the copolymer-based polyplexes in nude mice afforded detectable gene expression largely in the lung. Importantly, the copolymer revealed low cytotoxicity in vitro, as determined by AlamarBlue assay, and caused no death of the mice. Dextranated, bioreducible cationic polyamide holds high potential as a non-viral vector for gene delivery. PMID- 24211953 TI - Research of arginylglycylaspartic to promote osteogenesis of bone marrow mesenchymal cells on chitosan/hydroxyapatite scaffolds. AB - A high degree of cell adhesion to a scaffold at the initial stage of cell inoculation is essential to bone tissue engineering. In realising high cell adhesion rate on a scaffold within a few hours, a chitosan/hydroxyapatite (CS/HA) scaffold with a channel/sphere pore was prepared via in situ hybridisation in combination with lyophilisation, in which the HA nanoparticles were dispersed in the CS uniformly. The size of the channel pore and the sphere pore of the CS/HA scaffold was 150 MUm to 650 MUm and 3 MUm to 15 MUm, respectively. The compression strength and porosity of the CS/HA scaffold were 3.54 +/- 0.32 MPa and 88.4%, respectively. The nitrogen content increased by 7.5% compared with the CS/HA scaffold without Arg-Gly-Asp (RGD) modification. More than 67% of the RGD in the PBS solution diffused into the CS/HA scaffold spontaneously. The effect of the RGD peptide on bone marrow mesenchymal stem cells (MSCs) on the CS/HA scaffold was investigated through cell adhesion rate, alkaline phosphatase (ALP) activity, and mineralised calcium nodules. The cell adhesion rates of the CS/HA scaffold with different RGD concentrations (50, 100 mg/L) were 71.6% and 80.7%, respectively, after 4 hours of culture; the rates were 30.9% and 47.5% higher than that of the CS/HA group (54.7%), respectively. The expressed ALP content of the CS/HA scaffold with RGD (191 +/- 6 U/g protein) was 107.7% higher than that (92 +/- 9U/g protein) of CS/HA (p<0.01). Furthermore, a higher amount of mineralised calcium nodules with red brown appeared in the CS/HA scaffold with RGD as opposed to that in the CS/HA group. The RGD peptide in the CS/HA scaffold not only achieved high cell adhesion in a short period of time, but also enhanced cell adhesion ability and promoted the MSCs to differentiate from osteoblasts. PMID- 24211954 TI - Influence of sheath solvents on the quality of ethyl cellulose nanofibers in a coaxial electrospinning process. AB - The influence of different types of solvents as sheath fluids on the quality of electrospun ethyl cellulose (EC) nanofibers is investigated in this paper by a modified coaxial process. With 24 w/v % EC in ethanol as electrospinning core fluid and pure solvents including methanol, ethanol and N,N-dimethyl formamide (DMF) as sheath fluids, EC nanofibers were generated by the modified processes. Field emission scanning electron microscope observations demonstrate that the modified process is effective in improving the nanofibers' quality in terms of nanofibers' diameters, distributions and structural uniformity. The key of the modified coaxial process is the reasonable selection of the sheath solvents that is suitable for the drawing process of core EC fluid during the electrpospinning. The EC nanofibers' diameters (D, nm) could be manipulated through the reasonable selection of the type of the sheath solvents based on their boiling point (T, degrees C) D = 841-3.71T (R=0.9753). This paper provides useful methods for the implementation of the modified coaxial process controllably to obtain polymer nanofibers with high quality. PMID- 24211955 TI - Biological characteristics and oxidation mechanism of a new manganese-oxidizing bacteria FM-2. AB - A new manganese-oxidizing strain FM-2 was screened out from biological activated carbon (BAC) filter column and was identified as Citrobacter freundii. The results of the systematic study on this species are as follows: At 27 degrees C, the optimum pH for Citrobacter sp. FM-2 to remove manganese was 7.0-8.0.The best removal rate of manganese under 27 degrees C, pH 7.0 by FM-2 was reached at 4 d, being 76.2%; Compared with adsorption, biological oxidation played a dominant role in this removing process. Almost 75.7% of manganese was oxidized into oxides by Citrobacter sp and there were some particular oxides analogs generated on the bacterial surface; A 296bp DNA fragment amplified from Citrobacter sp. FM-2 revealed that this species has multicopper oxidase genes. Meanwhile, the phylogenetic tree indicated that compared with other related species, Citrobacter sp. FM-2 has its own evolutional independence. PMID- 24211956 TI - Study of the therapeutic effect of 188Re labeled folate targeting albumin nanoparticle coupled with cis-diamminedichloroplatinum cisplatin on human ovarian cancer. AB - This paper aimed to investigate the treatment efficiency of 188Re labeled folate targeting albumin nanoparticles with cis-Diamminedichloroplatinum Cisplatin (188Re-folate-CDDP/HAS MNP) on human ovarian cancer. SKOV3 cells or tumor-bearing mice were divided into different groups and treated as follow: (A) negative control; (B) chemotherapy; (C) radiotherapy; (D) hyperthermia; (E) chemotherapy and radiotherapy; (F) chemotherapy and hyperthermia; (G) radiotherapy and hyperthermia; (H) chemotherapy, radiotherapy and hyperthermia. Treatment of B to H inhibited proliferation of SKOV3 cells, with the greatest inhibition being observed in group H (P<0.05). Obvious apoptotic hypodiploid peak appeared beside G1 phase in groups of B to H. The apoptotic rates of SKOV3 cells in groups of A to H were 0.08%, 7.56%, 8.64%, 17.14%, 21.64%, 23.77%, 33.94% and 57.16%, respectively. Our findings in vivo study showed that the mass of tumor in each group of B to H was significantly lower than that in the negative control (p <0.05). In addition, compared with each group of B to G, group H showed highest inhibition of tumor growth (p<0.05). In conclusion, the combination of magnetic induced hyperthermia, chemotherapy and targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which indicates a potential applications in ovarian cancer treatment. PMID- 24211957 TI - Fluid dynamics aspects of miniaturized axial-flow blood pump. AB - Rotary blood pump (RBP) is a kind of crucial ventricular assist device (VAD) and its advantages have been evidenced and acknowledged in recent years. Among the factors that influence the operation performance and the durability of various rotary blood pumps, medium property and the flow features in pump's flow passages are conceivably significant. The major concern in this paper is the fluid dynamics aspects of such a kind of miniaturized pump. More specifically, the structural features of axial-flow blood pump and corresponding flow features are analyzed in detail. The narrow flow passage between blade tips and pump casing and the rotor-stator interaction (RSI) zone may exert a negative effect on the shear stress distribution in the blood flow. Numerical techniques are briefly introduced in view of their contribution to facilitating the optimal design of blood pump and the visualization of shear stress distribution and multiphase flow analysis. Additionally, with the development of flow measurement techniques, the high-resolution, effective and non-intrusive flow measurement techniques catering to the measurement of the flows inside rotary blood pumps are highly anticipated. PMID- 24211958 TI - Nucleation of hydroxyapatite on Antheraea pernyi (A. pernyi) silk fibroin film. AB - Antheraea pernyi (A. pernyi) silk fibroin, which is spun from a wild silkworm, has increasingly attracted interest in the field of tissue engineering. The aim of this study was to investigate the nucleation of hydroxyapatite (HAp) on A. pernyi fibroin film. Von Kossa staining proved that A. pernyi fibroin had Ca binding activity. The A. pernyi fibroin film was mineralized with HAp crystals by alternative soaking in calcium and phosphate solutions. Spherical crystals were nucleated on the A. pernyi fibroin film according to scanning electron microscopeimaging results. The FT-IR and X-ray diffraction spectra confirmed that these spherical crystals were HAp. The results of in vitro cell culture using MG 63 cells demonstrated that the mineralized A. pernyi fibroin film showed excellent cytocompatibility and sound improvement of the MG-63 cellviability. PMID- 24211959 TI - Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative. AB - The objective of this work was to evaluate the effect of decellularization and hyaluronic acid derivative on the improvement of anticalcification of glutaraldehyde fixed bovine pericardium (GFBP) using a rat subcutaneous implantation model A cell extraction process was employed to remove the cells and cellular components from bovine pericardium (BP), leaving a framework of largely insoluble collagen. Then acellular BP was cross-linked by glutaraldehyde solution and treated with hyaluronic acid derivative (HA-ADH) which was obtained by coupling adipic dihydrazide (ADH) on-COOH of hyaluronic acid (HA). The results of in vivo calcification tests showed that the calcium content was decreased dramatically by decellularization alone (from 28.07 +/- 18.87 to 2.44 +/- 0.55 MUg Ca/mg dry tissue after 8 weeks' implantation), and even less concentration was shown by the combination of HA derivative treatment and decellularization (GFaBP-HA group) (0.25 +/- 0.08 MUg Ca/mg dry tissue after 8 weeks' implantation). In addition, GFaBP-HA group not only presented a lower degree of calcification, but also showed lower ratios of Ca/P molar, which corresponded to amorphous calcium phosphates. The obtained results indicated that GFaBP-HA was a potential candidate for the manufacture of anticalcification bioprostheses. PMID- 24211960 TI - Hyaluronic acid as an internal phase additive to obtain ofloxacin/PLGA microsphere by double emulsion method. AB - Hyaluronic acid (HA) was used as an internal phase additive to improve the loading efficiency of ofloxacin, a hydrophilic drug encapsulated by hydrophobic polylactic-co-glycolic acid (PLGA) materials, through a double emulsion (water-in oil-in-water) solvent extraction/evaporation method. Results from laser distribution analysis show that polyelectrolyte additives have low impact on the average particle size and distribution of the microspheres. The negatively charged HA increases the drug loading efficiency as well as the amount of HA in microspheres. Burst release can be observed in the groups with the polyelectrolyte additives. The release rate decreases with the amount of HA inside the microspheres in all negatively charged polyelectrolyte-added microsphere groups. PMID- 24211961 TI - Rapid and sensitive controlled release monitoring method of biomedical combined products with IDM for pain management and cancer treatment. AB - New designed combined products and its determination for pain management and cancer treatment were studied. A rapid and sensitive stability indicating HPLC method had been developed and validated for the determination of Indomethacin(IDM) in a transdermal patch. This analytical method was successfully applied to the determination of Indomethacin in a transdermal patch and can be used for routine quality control analysis. Chromatographic separation was achieved isocratically on an Inertsil(r) C8-3 column utilizing a mobile phase of acetonitrile / 0.01 M monobasic sodium phosphate and 0.01 M dibasic sodium phosphate buffer (pH 3) (65:35, v/v) at the flow rate of 1 mL/min with UV detection at the wavelength of 210 nm. The system suitability was performed, and the result showed that Indomethacin(IDM) and its impurity were separated. The calibration curve of Indomethacin(IDM) was linear in the range of 0.1~15 ppm (r = 0.9989, n = 3). PMID- 24211962 TI - Feature selection using mutual information based uncertainty measures for tumor classification. AB - Feature selection is a key problem in tumor classification and related tasks. This paper presents a tumor classification approach with neighborhood rough set based feature selection. First, some uncertainty measures such as neighborhood entropy, conditional neighborhood entropy, neighborhood mutual information and neighborhood conditional mutual information, are introduced to evaluate the relevance between genes and related decision in neighborhood rough set. Then some important properties and propositions of these measures are investigated, and the relationships among these measures are established as well. By using improved minimal-Redundancy-Maximal-Relevancy, combined with sequential forward greedy search strategy, a novel feature selection algorithm with low time complexity is proposed. Finally, several cancer classification tasks are demonstrated using the proposed approach. Experimental results show that the proposed algorithm is efficient and effective. PMID- 24211963 TI - Development of an optical fiber sensor for angular displacement measurements. AB - For diagnostic and therapeutic purposes, the joint angle measurement of a patient after an accident or a surgical operation is significant for monitoring and evaluating the recovering process. This paper proposed an optical fiber sensor for the measurement of angular displacement. The effect of beveled fiber angle on the detected light signal was investigated to find an appropriate mathematical model. Beveled fiber tips redirected the light over a range of angles away from the fiber axis. Inverse polynomial models were applied to directly obtain and display the joint angle change in real time with the Lab-VIEW program. The actual joint angle correlated well with the calculated LabVIEW output angle over the test range. The proposed optical sensor is simple, cost effective, small in size, and can evaluate the joint angle in real time. This method is expected to be useful in the field of rehabilitation and sport science. PMID- 24211964 TI - Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin. AB - This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents. PMID- 24211965 TI - In vivo biodegradation of porous silk fibroin films implanted beneath the skin and muscle of the rat. AB - Since the bioresorption process has a strong impact not only on the mechanical properties of the biomaterial but also on the extent of tissue regeneration, in vivo biodegradation of absorbable porous biomaterials plays a key role in tissue repair and wound healing. In the present work, porous silk fibroin films (PSFFs) were prepared by a freeze-drying method and then implanted beneath the dorsal skin and the femoral skeletal muscle of the rat. The objective was to study the rate of biodegradation of the PSFFs in different tissues, each with its distinct metabolic rate. In addition we examined the relationship between the biodegradation rate and tissue-regeneration rate semi-quantitatively by incorporating histology, microscopy and image analysis methods. Furthermore, based on our previous findings, we also explored the relationship between in vitro and in vivo rates of biodegradation. The results suggest that the PSFFs experience a similar biodegradation process regardless of the type of tissue in which they are implanted, in spite of the higher metabolic rate of the skeletal muscle. In addition, the in vitro biodegradation rate of the PSFFs was comparable to that of both skin and skeletal muscle, suggesting that an in vitro biodegradation test could be used to predict in vivo performance. PMID- 24211966 TI - Biomimetic growth of bone-like apatite via simulated body fluid on hydroxyethyl cellulose/polyvinyl alcohol electrospun nanofibers. AB - In this study, randomly oriented hydroxyethyl cellulose/polyvinyl alcohol (HEC/PVA) nanofibers were fabricated by electrospinning. The blend solutions of HEC/PVA with different weight ratio of HEC to PVA were prepared using water as solvent to fabricate nanofibers. These nanofibrous scaffolds were coated with bone-like apatite by immersing into 10x simulated body fluid (SBF) for different time periods. The morphology and structure of the nanofibers were characterized by SEM, FTIR and DSC. FESEM-EDS and FTIR analysis were used to confirm the deposition of apatite on the surface of nanofibers. The results of this study suggest that this apatite coated nanofibrous scaffolds could be a suitable biomaterial for bone tissue engineering. PMID- 24211967 TI - Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy. AB - This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT. PMID- 24211968 TI - Mineralization and biocompatibility of Antheraea pernyi (A. pernyi) silk sericin film for potential bone tissue engineering. AB - This study aimed to investigate the mineralization of Antheraea pernyi (A. pernyi) silk sericin. Mineralization of A. pernyi sericin was performed by alternative soaking in calcium and phosphate. The inhibition of precipitation of calcium carbonate and von Kossa staining on A. pernyi sericin were tested, and the corresponding results prove that A. pernyi sericin has Ca binding activity. Scanning electron microscope (SEM) observation shows that spherical crystals could be nucleated on the A. pernyi sericin film. These crystals were confirmed to be hydroxyapatite according to FT-IR and XRD spectra, indicating that A. pernyi sericin is capable of mineralization. In addition, cell adhesion and growth activity assay demonstrate that A. pernyi sericin shows excellent biocompatibility for the growth of MG-63 cells. PMID- 24211969 TI - Molecular dynamics simulations for the examination of mechanical properties of hydroxyapatite/ poly alpha-n-butyl cyanoacrylate under additive manufacturing. AB - Molecular dynamics (MD) simulations emerged to be a helpful tool in the field of material science. In rapid prototyping artificial bone scaffolds process, the binder spraying volume and mechanism are very important for bone scaffolds mechanical properties. In this study, we applied MD simulations to investigating the binding energy of alpha-n-butyl cyanoacrylate (NBCA) on Hydroxyapatite (HA) crystallographic planes (001, 100 and 110), and to calculating and analyzing the mechanical properties and radial distribution function of the HA(110)/NBCA mixed system. The simulation results suggested that HA (110) has the highest binding energy with NBCA owing to the high planar atom density, and the mechanical properties of HA(110)/NBCA mixed system is stronger than pure HA system. Therefore, the multi-grade strength bone scaffold could be fabricated through spraying various volume NBCA binders during 3D printing process. By calculating the radial distribution function of HA(110)/NBCA, the essence of the interface interaction were successfully elucidated. The forming situation parameters can be referred to calculation results. There exists a strong interaction between HA crystallographic plane (110) and NBCA, it is mainly derived from the hydrogen bonds between O atoms which connect with C atoms of NBCA and H atoms in HA crystal. Furthermore, a strong adsorption effect can be demonstrated between HA and NBCA. PMID- 24211970 TI - Microencapsulated rBMMSCs/calcium phosphate cement for bone formation in vivo. AB - As an injectable scaffold material for bone tissue engineering, calcium phosphate cement (CPC) has good biocompatibility, self-setting, and osteoconduction properties. Alginate-microencapsulated seed cells can pick up the degradation speed and bioactivity of CPC. The aim of this study was to explore the osteogenic ability of a composite of microencapsulated rabbit bone marrow mesenchymal stem cells (rBMMSCs) with beta-tricalcium phosphate/calcium phosphate cement (beta TCP/CPC) in vivo. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. beta-TCP/CPC (control group) and alginate microencapsulated rBMMSCs/beta-TCP/CPC composite (composite group) were implanted separately into the bone defects of both femurs. Bone substitute degradation and new bone formation were evaluated by CBCT, and the defects were examined histologically 8, 16, and 24 weeks after implantation. In addition, fluorescent carbocyanine CM-Dil was used to track the rBMMSCs in vivo after implantation. The results showed that far more new bone and bone marrow grew into the bone defects in the composite group. Few CM-Dil labeled positive cells were observed postoperatively. However more native cells were detected in the graft areas of the composite group than those of the control group. The study indicates that a composite of microencapsulated seed cells/beta-TCP/CPC might be considered as a promising injectable material for the generation of new bone tissue. PMID- 24211971 TI - Study on human promyelocytic leukemia HL-60 cells apoptosis induced by fucosterol. AB - In this study, we investigated the effect of fucosterol on HL-60 and the molecular mechanism. HL-60 Cells were treated with fucosterol, and 3-(4, 5 Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was used to study fucosterol anti-tumor activity. Morphology of HL-60 cells was observed. Flow cytometry (FCM) was employed to detect the cell cycle. Laser scanning confocal microscope (LSCM) was used to analyze mitochondrial membrane potential (MMP) and the expressions of Fas, FasL, Fadd and Caspase-8. Western blot was performed to analyze the expressions of Cyt-C, Pro-Caspase-9 and Pro-Caspase-3. Caspase activity kits were used to determine the activity of Caspase-9, Caspase-8 and Caspase-3. The results showed fucosterol could inhibit the growth of HL-60 cells, and the cell cycle was arrested at G2/M phase. HL-60 cells showed obvious apoptosis morphology. After being treated with fucosterol for 24 h, HL-60 cells decreased MMP, induced Cyt-C release and Caspase-9, Caspase-3 activation. Fucosterol also increased the protein expression of Fas, FasL, Fadd and Caspase 8. Moreover, the activity of Caspase-9, Caspase-8 and Caspase-3 was increased significantly. In conclusion, Fucosterol can induce HL-60 cells apoptosis, suggesting that it may be a potent agent for cancer prevention and treatment. PMID- 24211972 TI - Comparison between experimentally measured flow patterns for straight and helical type graft. AB - The long-term success of arterial bypass surgery is often limited by the progression of intimal hyperplasia at the anastomosis between the graft and the native artery. The experimental models were manufactured from glass tubing with constant internal diameter of 8 mm, fashioned into a straight configuration and helical configuration. The aim of this study was to determine the three dimensional flow structures that occur at the proximal anastomosis under pulsatile flow conditions, to investigate the changes that resulted from variations in the anastomosis angle and flow division, and to establishing the major differences between the straight and helical graft. In the anastomosis domain, a strong region of recirculation is observed near the occluded end of the artery, which forces the flow to move into the perfused host coronary artery. The proximal portion of the host tube shows weak counter-rotating vortices on the symmetry plane. The exact locations and strengths of the vortices in this region are only weakly dependent on Re. A detailed comparison of experimentally measured axial velocity patterns for straight and helical grafts confirm the very strong nature of the secondary flows in the helical geometry. The helical configuration promotes the mixing effect of vortex motion such that the flow particles are mixed into the blood stream disal to the anastomotic junction. PMID- 24211973 TI - A model to calculate microstreaming-shear stress generated by oscillating microbubbles on the cell membrane in sonoporation. AB - The shear stress exerted on the cell membrane is an important factor in sonoporation. However, almost all previous calculations of shear stress were based on the Rooney's assumption, which is not applicable for the sonoporation experiments. In the article, to construct the microstreaming-shear stress model in sonoporation, it theoretically analyzed the microstreaming-shear stress exerted on the cell membrane generated by oscillating microbubble based on Nyborg's acoustic streaming theory. And the response of the model was compared with that of the sonoporation experiment. Cells were exposed by 1MHz 150 kPa ultrasound in the presence of SonoVue(r) microbubbles. The sonoporated cells were labeled by fluorescent markers and detected by fluorescence microscopy and flow cytometry. The theoretically analyzed microstreaming-shear stress was in accordance with the cell experimental result. Although some minor factors are ignored when building the model to calculate the microstreaming-shear stress, the model was still reasonable. PMID- 24211974 TI - TLR4 signaling pathway in mouse Lewis lung cancer cells promotes the expression of TGF-beta1 and IL-10 and tumor cells migration. AB - The signaling pathways that trigger tumor cell escape from immune surveillance are not understood completely. Toll-like receptors (TLRs) are considered to be expressed in both immune cells and tumor cells. By detecting TLRs expression in mouse Lewis lung cancer (LLC) before and after co-culture with mouse lymphocytes, the authors concluded that LLC cells constitutively expressed TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 and TLR9. Meanwhile, TLR4 expression in LLC cells was the strongest after co-culture with mouse lymphocytes. To investigate the possible roles of TLR4 signaling pathway in LLC, the concentrations of TGF-beta1 and IL-10 protein in LLC cells supernatant were detected by ELISA, and the migration of LLC cells were detected by transwell assay after lipopolysaccharide (LPS) stimulation. TLR4 protein expression in LLC cells was also detected after LPS stimulation by FCM. The results indicated that both levels of TGF-beta1 and IL-10 protein were significantly increased after LPS stimulation and reached to a maximum at 24 h and 10 MUg/mL of LPS. The migrated LLC cells with LPS stimulation were significantly increased and reached to a maximum at 10 MUg/mL of LPS. The expression of TLR4 protein was significantly enhanced after 10 MUg/mL of LPS stimulation. These results suggest that the activation of TLR4 signaling pathway in lung cancer cells may be involved in tumor escape and progression by promoting the expression of TGF-beta1 and IL-10 and tumor cells migration. PMID- 24211975 TI - Transcriptional suppression of human apolipoproteinA4 and apolipoproteinC3 genes by phorbol myristate acetate in hepatic and intestinal cells. AB - BACKGROUND: Genetic, epidemiological and clinical evidence has demonstrated the importance of the human apolipoproteinA5 (apoA5), apolipoproteinA4 (apoA4), apolipoproteinC3 (apoC3), and apolipoproteinA1 (apoA1) genes in the control of the triglyceride and cholesterol concentrations in the blood. However, little is known about the mechanism by which protein kinase C (PKC) regulates the expression of these genes in hepatic and intestinal cells. The aim of this study was to explore the regulatory role of PKC on the expression of apoA5, apoA4, apoC3 and apoA1. METHODS: Hepatic HepG2 and intestinal Caco-2 cells were treated with a potent PKC activator, Phorbol myristate acetate (PMA). The real time quantitative RT-PCR (qRT-PCR) technique was used to evaluate the effects of PMA on the expression of apoA1, apoA4, apoA5 and apoC3 genes. Nuclear run on assay was used to determine whether the effect of PMA on apoA4 and apoC3 was due to its ability to regulate the transcription of these genes. RESULTS: PMA specifically down-regulated the transcription of apoA4 and apoC3, but exhibited no effects on apoA1 or apoA5 in either HepG2 or Caco-2 cells. Further study by nuclear run on assay proved that the suppressive effect of PMA on apoA4 and apoC3 resulted from PMA's regulation of the transcription rate of the two genes. CONCLUSIONS: PMA down-regulated transcription of apoA4 and apoC3 possibly through the common regulatory element shared by these two genes, suggesting a suppressive role of PKC on the transcriptional regulation of specific apolipoproteins in hepatic and intestinal cells. PMID- 24211976 TI - The preparation of gold nanoparticles and evaluation of their immunological function effects on rats. AB - As a new type of biomaterials, gold nanoparticles (GNPs), also known as colloidal gold (CG), have a wide biomedical application. In this study, GNPs with diameters of 10, 15, and 25 nm were prepared by sodium citrate reduction, and detected by common optical property, ultraviolet-visible (UV-vis) absorbance spectroscopy, and scanning electron microscope (SEM), separately for identification of the particle size and uniformity. In order to observe the effects of GNPs on immune function, adult Sprague Dawley (SD) rats were immunized with the above three GNPs, each having three doses of 0.2, 0.4, and 0.6 ml, and rats without immunization served as negative control. After immunization, proliferation activity of blood and spleen lymphocyte and the levels of interleukin-2 (IL-2) in serum and supernatant of spleen lymphocyte were detected by thiazoleblue (MTT) assay and enzyme linked immunosorbent assay (ELISA), respectively. The results indicated that different size of GNPs was prepared, and the uniformity increased with the decrease of the size of particles. Different diameters and doses of GNPs have different effects on proliferation of blood and spleen lymphocyte, as well as the levels of IL-2 in serum and supernatant of spleen lymphocyte. The 15 nm CG in 0.6 ml dose group could most significantly promote blood and spleen lymphocyte proliferation, and enhance IL-2 levels in serum and supernatant of spleen lymphocyte. Taken together, the findings revealed that application of CG prepared by sodium citrate reduction could enhance specific and nonspecific immune responses, and the 0.6 ml dose of 15 nm CG might be the best immunizing dose in rats. This fact may serve as a further evidence for using CG as a novel immunoadjuvant in the future. PMID- 24211977 TI - Vulnerability during short-term memory induced response in canine ventricle. AB - Cardiac short-term memory is an intrinsic property which can make the action potential duration produce a transient response after a sudden change in heart rate. The change of vulnerability was investigated by using computer simulation method during the transient period which was created by abruptly shortening the cycle length from 800ms to 300ms. The study was performed on a heterogeneous fiber consisting of endo-, mid-, and epi-cardiac canine myocytes. An OpenMP parallel algorithm was used to accelerate the calculation. The study shows that the vulnerable window (VW) relied on both pacing times and locations. At the cycle length of 300ms, compared with the situation of 500th beat, there was a large transmural dispersion of repolarization (TDR) at the 30th beat. For most of the sites along the fiber, VW consistently demonstrated widely at the beginning of the transient period. Generally, with sustained pacing, VW tended to become small. The results suggested that during a memory-induced transient response, the probability of an occurrence of reentrant wave increased immediately after an abrupt change in pacing rate because of the relatively large TDR and VW within this period. Therefore, avoidance of a sudden heart rate variation was indicated to be helpful for the suppression of reentrant arrhythmias. PMID- 24211978 TI - Effects of Mn (II) on peroxynitrite nitrifying fibrinogen. AB - Fibrinogen is a plasma glycoprotein that is an established cardiovascular risk and it participates in the blood-clotting mechanism. Nitrated fibrinogen has been shown to inhibit platelet aggregation and thrombus formation. However, there are only a few reports relating to the activity and structural changes of nitrified fibrinogen when metal ions are present in the reaction. Mn (II) ion plays an important physiological role in the nervous system and cardiac function. In this study, we use UV-Vis, 3D-fluorescence, SDS-PAGE electrophoresis and Von-Clauss to detect 3-nitrotyrosine (3-NT) production and the activity changes of fibrinogen after nitration and oxidation damage caused by ONOO- in the presence of Mn (II). Results showed that Mn (II) can enhance the production of 3-NT in fibrinogen, promote fluorescence quenching of fibrinogen, and increase the injury to gamma and Aalpha chains of fibrinogen in the presence of peroxynitrite. Consequently, Mn (II) promotes concentration dependent fibrinogen nitrification damage and significantly reduces the biological activity of nitrified fibrinogen. PMID- 24211979 TI - Developmental toxicity of doxorubicin hydrochloride in embryo-larval stages of zebrafish. AB - Doxorubicin hydrochloride is widely used to treat various types of cancers. Its therapeutic and side effects are well documented. However, the developmental toxicity of doxorubicin has not been previously described. Lethal and sublethal effects on embryo-larval stages of zebrafish in a study of the developmental toxicity of doxorubicin were observed. Zebrafish embryos were exposed to different concentrations (0-100 mg/L) of doxorubicin between 4 and 120 h post fertilization, and zebrafish larvae were exposed to different concentrations (0 200 mg/L) of doxorubicin for 96 h. The markers about the development toxicity of doxorubicin in zebrafish were observed under a stereomicroscope. Higher doxorubicin concentrations mainly caused acute lethal effects, and lower doxorubicin concentrations mainly caused sublethal effects, such as multiple malformations in embryos and larvae. Moreover, with the increase of doxorubicin concentration, the malformation rate increased. The heart rate of embryos was accelerated at lower concentrations of doxorubicin (<= 10 mg/L) and decelerated at higher concentrations (>= 25 mg/L). The hatching rate and body length were inhibited at higher concentrations of doxorubicin (>= 25 mg/L).In conclusion, doxorubicin has serious developmental toxicity and this raises a concern for developmental effects of doxorubicin in clinical practice. PMID- 24211980 TI - Enhanced oral bioavailability and antiasthmatic efficacy of curcumin using redispersible dry emulsion. AB - Dry emulsion containing curcumin (DE-CUR) was prepared for oral delivery of poorly water-soluble curcumin, and its oral bioavailability and antiasthmatic efficacy was evaluated. After comparison of the solubility of curcumin in various oils, Plurol(r) Oleique CC497 was selected to be the oil phase due to its higher solubility of CUR than other oils. A dry emulsion prepared by spray-drying of a homogenized oil-in-water emulsion was well-reconstituted in water, fabricating similar particle distribution and in vitro release to that of a dispersed homogeneous emulsion before spraying. The release of DE-CUR was much higher than that of curcumin (85.3 vs. 1.7% release at 60 min). Consequently, DE-CUR resulted in 12.0- and 7.1-fold higher Cmax and AUC0-24h than curcumin. In a murine asthma model, DE-CUR effectively suppressed airway hyperresponsiveness and levels of T helper cytokines such as interleukin-4, inteleukin-5, and interleukin-13. These findings demonstrate that the DE-CUR shows a potential for the development of functional foods or medicines including CUR. PMID- 24211981 TI - Investigation on the decolorizing mechanism of Pseudomonas sp. R1 on reactive red X-3B. AB - A strain of Pseudomonas aeruginosa (Pseudomonas sp. R1), which can efficiently decolorize reactive red X-3B, was isolated from activated sludge in a dye plant, and the decolorizing mechanism was explored in this paper. The result shows that Pseudomonas sp. R1 has very good capability for decolorization of reactive red X 3B and the decolorization rate is increased by 9.1% after optimization of the experimental parameters, which means that 89.6% of the reactive red can be removed. Investigation on decolorization mechanism showed that the decolorizing capability of Pseudomonassp. R1 was significantly affected after plasmids in Pseudomonassp. R1 were eliminated by acridine orange (AO). Meanwhile, E. coli DH5a could gain decolorizing capability after transformed with the plasmids. Plasmid elimination and transformation tests proved that the decolorizing gene in Pseudomonas sp. R1 exists in the plasmid. PMID- 24211982 TI - Measuring temporal dynamics of resting-state fMRI data. AB - Resting state functional MRI (rs-fMRI), which is used to measure blood oxygen level-dependent (BOLD) from resting brains, is a relatively new and powerful method for evaluating regional interactions that occur when a participant is not performing an explicit task. Because of the sensitiveness to the phase shift and length of time courses of the BOLD recordings, region of interest based conventional correlation and coherence methods are no longer suitable for rs-fMRI analyses. In this paper, we propose a more robust and consistent method, dominant frequency mapping, to analyze rs-fMRI data. We found a dominant frequency of BOLD recordings, 0.0137 Hz, in resting human brains that is consistent across participants and brain regions. This frequency is detected mainly in Gyrus Rectus, Frontal Medial Orbital, Frontal Superior Orbital and Olfactory Sulcus, which control the human social behavior, emotion, and decision making. In the meantime, we found that BOLD frequencies are most inconsistent in the brain regions of PrecentralGyrus, Superior Frontal gyrus, Insula, Caudate nucleus, Putamen, and part of the cerebellum, whose functions are about motor. PMID- 24211983 TI - Diaphragm breathing movement measurement using ultrasound and radiographic imaging: a concurrent validity. AB - Recent ultrasound imaging evidence asserts that the diaphragm is an important multifunctional muscle to control breathing as well as stabilize the core and posture in humans. However, the validity and accuracy of ultrasound for the measurement of dynamic diaphragm movements during breathing and functional core activities have not been determined. The specific aim of this study was to validate the accuracy of ultrasound imaging measurements of diaphragm movements by concurrently comparing these measurements to the gold standard of radiographic imaging measurements. A total of 14 asymptomatic adults (9 males, 5 females; mean age =28.4 +/- 3.0 years) were recruited to participate in the study. Ultrasound and radiographic images were used concurrently to determine diaphragm movement (inspiration, expiration, and excursion) during tidal breathing. Pearson correlation analysis showed strong correlations, ranging from r=0.78 to r=0.83, between ultrasound and radiographic imaging measurements of the diaphragm during inhalation, exhalation, and excursion. These findings suggest that ultrasound imaging measurement is useful to accurately evaluate diaphragm movements during tidal breathing. Clinically, ultrasound imaging measurements can be used to diagnose and treat diaphragm movement impairments in individuals with neuromuscular disorders including spinal cord injuries, stroke, and multiple sclerosis. PMID- 24211984 TI - Qualitative and quantitative analysis of seven oligosaccharides in Morinda officinalis using double-development HPTLC and scanning densitometry. AB - The quality of Morindaofficinalis, which has been used as a Yang-tonic agent for a long time in China, can be evaluated. A double-development high performance thin layer chromatography (HPTLC) method has been established to simultaneously analyze quality and quantity of seven inulin-type oligosaccharides (DP=3-9) in Morindaofficinalis. The chromatography was performed on a silica gel 60 plate with the 7:5:2:1 proportion (v/v) of n-butanol-isopropanol-water-acetic acid for the first and second developments, respectively. The bands were visualized by the reaction with aniline-diphenylamine-phosphoric acid solution and analyzed by densitometric TLC at 540 nm. Quantification of seven oligosaccharides was achieved by densitometry at 540 nm. The investigated standard sugar had good linearity (R2>0.99) within test ranges. The amounts of seven oligosaccharides were calculated by the relative correction factor (RCF). Therefore, the developed TLC method could be used for quality control of Morindaofficinalis. PMID- 24211985 TI - Study of parameters for evaluating the pushability of interventional devices using box-shaped blood vessel biomodels made of PVA-H or silicone. AB - In this paper, we investigated several parameters with effect on the compressive force to assess the mechanical properties of interventional device. We find several parameters are highly influential and others are not. In our evaluation system, we prepared a box-shaped PVA-H and silicone with realistic geometry and carried out the measurement and evaluation of the pushability by using load cell machine. The parameters of velocity, position of device in the system do not affect the compressive force, whereas the length of catheter from the tip to fixed point is one of the most influential parameters for the force. Several behaviors such as passing through the curve or slip and stop can be observed and defined using this system. The balance of the bending force and the pushing force may make the tip with behavior of slip and stop or passing thorough the curve. The investigation of the evaluation system confirmed that high reproducibility with short error bar is indicated. The observation with movie record is also an advantage of our system because the high transparency of materials with silicone and PVA-H can check the inside of artery. PMID- 24211986 TI - Application of high-speed counter-current chromatography for isolation of triterpenes from Schisandra Chinensis (Turcz.) Baill and induction apoptosis mechanism of HSC-T6. AB - Triterpenes have shown many beneficial activities in researches, but their separation and preparation usually require multiple methods. Following an initial cleaning-up step on the AB-8 macroporous resin, a preparative high-speed counter current chromatography (HSCCC) with a two-phase solvent system comprising chloroform-n-butyl alcohol-methanol-water (10:1:7:4, v/v/v/v) was used to isolate and separate triterpenes from caculis of Schisandra Chinensis (Turcz.) baill. A total of 89 mg corosolic acid with purities of 98.5% were obtained from 400 mg crude extract in one-step elution and less than 4 h, and the structure identification was performed by UV, IR, MS, 1H NMR and 13C NMR. The inhibition on liver fibrosis activities of the triterpenes against HSC-T6 in vitro were studied by cell culture methods. The results showed that the corosolic acid have better inhibitory effects on HSC-T6 cells with the IC50 value of 5~25 MUg/mL and the study also indicated that corosolic acid might be a potential Chinese medical component to inhibit liver fibrosis. PMID- 24211987 TI - Osteogenic activity of nanonized pearl powder/poly (lactide-co-glycolide) composite scaffolds for bone tissue engineering. AB - Numerous materials have been proposed for bone tissue engineering. In this study, a newly designed hybrid composite scaffold composed of poly (D,L-lactide-co glycolide) and a naturally bioceramic hybrid material, nanonized pearl powder, were prepared and the biological activities and physical properties of the scaffold for bone tissue engineering were evaluated. It is a composite consisting calcium carbonate crystal in an aragonite structure, embedded in an organic matrix. Peral contains one or more signal molecules capable of stimulating bone formation. The nanonized pearl powder is considered as a promising osteoinductive biomaterial. This biomaterial is biocompatible and shows osteogenic activity. In this study, the designed biohybrid of nanonized pearl powder/poly (lactide-co glycolide) (NPP/PLGA) biocomposite scaffolds would employ biodegradable material as MC3T3-E1 cells seeded scaffolds. Therefore, the biocomposite scaffolds would be used to culture with MC3T3-E1 cells under spinner bioreactor in vitro. Furthermore, it also detailed how these tissues were characterized, qualitatively and quantitatively, with scanning electron microscopy and biochemical testing. The identity and the mode of action of these molecules on the osteoblast differentiation were analyzed. This study indicates that the efficiency of nanonized pearl powders in bone cell differentiation are certainly different from that of proteins. Further sudy will look forward to manufacturing the promising new generation bone substitute, three dimensional biocomposite scaffolds to replace the implant and autogeneous bone graft, which combines basic research and clinical application. PMID- 24211988 TI - Response time of visual matching task and heart rate in children with Attention Deficit Hyperactivity Disorder (ADHD). AB - The purpose of this study was to investigate the relation between response time of visual matching task and heart rate (HR) in children with Attention Deficit Hyperactivity Disorder (ADHD). Thirty boys who were diagnosed with ADHD and are under treatment participated in the study. The experiment consisted of three phases, a total of 5 min with rest phase, control phase, and visual matching task phase. HR was measured during each phase. The HR in visual matching task phase increased, compared to that in rest phase. There was a negative correlation between response time of visual matching task and magnitude of the HR in the visual matching task phase. In other words, as HR increased, response time of the visual matching task decreased. This means that increasing in HR increased the supply of oxygen by fast circulation of blood for cognitive processing and this induced the improvement of cognitive ability in the ADHD children. This means that increasing HR increased the supply of oxygen by fast circulation of blood for cognitive processing and this induced the improvement of cognitive ability in the ADHD children. The result of this study supports previous studies that the administration of high oxygen concentration can positively affect the cognitive performance of the ADHD children. The results of the present and previous studies also may provide scientific evidence that can be used for treating patients with cognitive problems such as ADHD. PMID- 24211989 TI - Non-contact physiological signal detection using continuous wave Doppler radar. AB - The aim of this work is to show non-contact physiological signal monitoring system based on continuous-wave (CW) Doppler radar, which is becoming highly attractive in the field of health care monitoring of elderly people. Two radar signal processing methods were introduced in this paper: one to extract respiration and heart rates of a single person and the other to separate mixed respiration signals. To verify the validity of the methods, physiological signal is obtained from stationary human subjects using a CW Doppler radar unit. The sensor operating at 24 GHz is located 0.5 meter away from the subject. The simulation results show that the respiration and heart rates are clearly extracted, and the mixed respiration signals are successfully separated. Finally, reference respiration and heart rate signals are measured by an ECG monitor and compared with the results tracked by the CW Doppler radar monitoring system. PMID- 24211990 TI - An ensemble feature selection technique for cancer recognition. AB - Correlation-based feature selection (CFS) using neighborhood mutual information (NMI) and particle swarm optimization (PSO) are combined into an ensemble technique in this paper. Based on this observation, an efficient gene selection algorithm, denoted by NMICFS-PSO, is proposed. Several cancer recognition tasks are gathered for testing the proposed technique. Moreover, support vector machine (SVM), integrated with leave-one-out cross-validation and served as a classifier, is employed for six classification profiles to calculate the classification accuracy. Experimental results show that the proposed method can reduce the redundant features effectively and achieve superior performance. The classification accuracy obtained by our method is higher in five out of the six gene expression problems as compared with that of other classifi cation methods. PMID- 24211991 TI - A 1-channel 3-band wide dynamic range compression chip for vibration transducer of implantable hearing aids. AB - In this paper, a digital audio processing chip which uses a wide dynamic range compression (WDRC) algorithm is designed and implemented for implantable hearing aids system. The designed chip operates at a single voltage of 3.3V and drives a 16 bit parallel input and output at 32 kHz sample. The designed chip has 1 channel 3-band WDRC composed of a FIR filter bank, a level detector, and a compression part. To verify the performance of the designed chip, we measured the frequency separations of bands and compression gain control to reflect the hearing threshold level. PMID- 24211992 TI - Licochalcone A inhibiting proliferation of bladder cancer T24 cells by inducing reactive oxygen species production. AB - The aim of this study was to determine the relationship between proliferation inhibition and the production of reactive oxygen species (ROS) induced by Licochalcone A (LCA). Cell viability was evaluated using sulforhodamine B (SRB) assay. Intracellular ROS level was assessed using the 2, 7-dichlorofluorescein diacetate (H2DCFDA) probe and dihydroethidium (DHE) probe assay. The results indicate that LCA inhibits human bladder cancer T24 proliferation in a concentration-dependent manner, with an IC50 value of approximately 55 MUM. The LCA-induced ROS production is inhibited by the co-treatment of LCA and free radical scavenger N-acetyl-cysteine (NAC), on the contrary, the proliferation rate and ROS production increase when treated by the combination of LCA and L buthionine-(S,R)-sulfoximine (BSO). The ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) decreases in a concentration-dependent manner. The results suggest that LCA inhibits proliferation by increasing intracellular ROS levels resulted in an oxidative stress status in T24 cells. PMID- 24211993 TI - Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study. AB - As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space. PMID- 24211994 TI - Electroencephalogram synchronization analysis for attention deficit hyperactivity disorder children. AB - This study investigated the changes in synchronization of different electroencephalogram (EEG) bands in attention deficit hyperactivity disorder (ADHD) children. EEG data were obtained from 13 children diagnosed with ADHD and 13 normal control children in the resting state. The statistical dependencies between each EEG channel were generated by calculating synchronization likelihood. The differences of synchronization between the ADHD and control groups were statistically evaluated. Overall, the synchronization was significantly higher in the ADHD group in the alpha and beta bands. The present study found that synchronization was significantly altered in the fast EEG bands in patients with ADHD. These findings may enhance our understanding for the relationship between ADHD and cerebral dysfunction. PMID- 24211995 TI - A Hurst exponent estimator based on autoregressive power spectrum estimation with order selection. AB - The discrete-time fractional Gaussian noise (DFGN) has been proven to be a regular process. According to Wold and Kolmogorov theorems, this process can be described as an autoregressive (AR) model of an infinite order. An estimator for the Hurst exponent based on autoregressive power spectrum estimation has been proposed, but without considering order selection. In this paper, six common order selection methods for the AR model were used to select appropriate orders of the AR model in order to raise the accuracy of estimating the Hurst exponent. Experimental results show that these six AR methods with considering order selection are more accurate than the original AR method without considering order selection. PMID- 24211996 TI - Numerical validation of a suprasystolic brachial cuff-based method for estimating aortic pressure. AB - Central aortic pressures are better predictors of cardiovascular events than peripheral pressures. However, central aortic blood pressures cannot be measured noninvasively; for this reason, estimating aortic pressures from noninvasive measurements of peripheral pressures has been the subject of numerous studies. In the present study, a novel method was proposed to noninvasively estimate aortic pressures from the oscillometric wave of a suprasystolic brachial cuff. The errors of estimation were evaluated in relation to various cardiovascular properties using an integrated cardiovascular-cuff model. Obtained results demonstrated that the estimation errors are affected mainly by aortic stiffness. The estimation errors for aortic systolic pressure, diastolic pressure, pulse pressure and wave shape under the assumed cardiovascular conditions were 5.84 +/- 1.58 mmHg, -0.28 +/- 0.41 mmHg, 6.12 +/- 1.42 mmHg and 1.72 +/- 0.57 mmHg, respectively, all of which fell within the error ranges established by existing devices. Since the method is easy to be automated and bases the estimation fully on patient-specific information, its clinical application is promising, although further clinical studies are awaited to validate the method in vivo. PMID- 24211997 TI - Study of brain functional network based on sample entropy of EEG under magnetic stimulation at PC6 acupoint. AB - Acupuncture is based on the theory of traditional Chinese medicine. Its therapeutic effectiveness has been proved by clinical practice. However, its mechanism of action is still unclear. Magnetic stimulation at acupuncture point provides a new means for studying the theory of acupuncture. Based on the Graph Theory, the construction and analysis method of complex network can help to investigate the topology of brain functional network and understand the working mechanism of brain. In this study, magnetic stimulation was used to stimulate Neiguan (PC6) acupoint and the EEG (Electroencephalograph) signal was recorded. Using non-linear method (Sample Entropy) and complex network theory, brain functional network based on EEG signal under magnetic stimulation at PC6 acupoint was constructed and analyzed. In addition, the features of complex network were comparatively analyzed between the quiescent and stimulated states. Our experimental results show the topology of the network is changed, the connection of the network is enhanced, the efficiency of information transmission is improved and the small-world property is strengthened through stimulating the PC6 acupoint. PMID- 24211998 TI - Establishment of dsDNA/GNs/chit/GCE biosensor and electrochemical study on interaction between 6-mercaptopurine and DNA. AB - In this paper, the anti-cancer drug 6-mercaptopurine (6-MP) was taken as the detection object. The biosensor of dsDNA/GNs/chit/GCE was established using the grapheme (GNs) and chitosan (chit) as the compound modified material. The electrochemical behavior of 6-MP on the sensor was discussed, and the damage and its mechanism of 6-MP on DNA were studied. The experimental result showed that, after the modification of GNs-chit, the electrode activation area of GNs/chit/GCE increased remarkably, which was improved from 1.76cm2 to 8.64 cm2, and the responsive oxidation peak current of GNs/chit/GCE to K3[Fe(CN)6] also increased remarkably. At the meantime, it was demonstrated that DNA was effectively fixed on the GNs/chit/GCE electrode;6-MP caused obvious damage to dsDNA, and the damage degree on the adenine was bigger than that on the guanine; the interaction between 6-MP and dsDNA was preliminarily deduced as the intercalation, and its electrochemical oxidation process was an irreversible process controlled by the adsorption. PMID- 24211999 TI - Direct electron transfer of horseradish peroxidase on a functional nanocomplex modified glassy carbon electrode. AB - Direct electron transfer of horseradish peroxidase (HRP) was achieved by immobilizing HRP on a functional nanocomplex modified glassy carbon (GC) electrode. The cyclic voltammograms (CVs) of the modified electrode have a pair of well-defined redox peaks with a formal potential (E degrees ') of -26 +/- 2 mV versus Ag/AgCl, in 0.05 M, pH7.0 phosphate buffer solution (PBS) at a scan rate of 0.05 V/s. The heterogeneous electron transfer constant (ks) was calculated to be 1.94 s-1. The modified electrode response toward hydrogen peroxide was linear in the concentrations ranging from 0.28 MUM to 10 MUM, with a detection limit of 0.28 MUM. The apparent Michaelis-Menten constant (Kmapp) for H2O2 was 2.54 MUM. Moreover, results of biochemical computation showed that the amino acid residues (Ala34, Arg38, Ser73, Arg75, Ala140, Pro141, Phe172, Gly173, Lys174, Phe179, Arg31, Ser35, Lys174, Gln176) of HRP may playa crucial role in the improvement of electron transport between electro-active site (heme group) of an HRP molecule and nanocomplex modified GC electrode. PMID- 24212000 TI - A molecule-imprinted polyaniline membrane modified on carbon fiber for detection of glycine. AB - A layer of L-glycine-molecule-imprinted polyaniline (LMIP-PANI) polymer film has been modified on a carbon fiber electrode for the determination of L-glycine standard samples and L-glycine in cerebrospinal fluid of wistar mice. It has been found that a linear relationship exists between current and concentration for the glycine standard samples in the range of 0-12 MUM by using the LMIP-PANI-modified carbon fiber electrode as a sensor. However, there is no any relationship between current and concentration for the carbon fiber electrode modified with no-glycine molecule-imprinted polyaniline (NIP-PANI). The MIP-PANI- and NIP-PANI-modified carbon fiber films have been characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and electrochemistry methods. The investigation shows that the MIP-PANI-imprinted carbon fiber electrode will have a potential application in in-situ monitoring neurotransmitter due to its easy fabrication, low cost, bio-compatibility and flexibility. PMID- 24212001 TI - Analysis of the strain of the great saphenous vein in motion. AB - This research probes into the strain changes of the great saphenous vein (GSV) during step exercises. Microelectromechanical Systems (MEMS) were used to process and develop Gauge Factors (GF=4.79 +/- 0.247), 5 males and 5 females with an average age of 20 +/- 0.6 years were asked to engage in step exercises (with step height of 25 cm), and the strain changes of the GSV in the lower limbs of the dorsal venous arch were measured. The results show that the effect the exercise has on the vein vessel is not prominent within 0.87 min; between 0.87 and 13.71 min, the average rates of the strain changes in the GSV show a linear increase; after 13.4 +/- 0.31 min, the linear curve of the increase rate is alleviated. This shows that to prevent varicose veins in the lower limbs, continuous exercise between 0.87 to 13.71 minutes has better effects in training. Exercising for over 13.71 minutes has its beneficial effects, but the effects are considerably less obvious than exercising for 0.87~13.71 min. PMID- 24212002 TI - Improve GRAPPA with cross-sampled ACS lines and nonlinear kernel model. AB - Among the methods of parallel magnetic resonance imaging (PMRI), Generalized Auto calibrating Partially Parallel Acquisitions (GRAPPA) technique reconstructs the missing k-space data by a set of weights, which are derived from auto-calibration signal (ACS) lines acquired in parallel to the reduced lines. In this paper, a novel hybrid method is proposed to reconstruct by cross sampling the ACS lines orthogonal to the reduced lines and estimating weights with a second-order nonlinear model. The proposed method can mix the benefits of cross sampling and the nonlinear kernel model. The in vivo experiments demonstrate this method, named as cross-sampled nonlinear (CSNL) GRAPPA, can effectively reduce the aliasing artifacts and noises when high acceleration is desired. PMID- 24212003 TI - Acceleration method of 3D medical images registration based on compute unified device architecture. AB - Compute Unified Device Architecture (CUDA) is a parallel computing platform and programming model invented by NVIDIA. It enables dramatic increase in computing performance via the power of the graphics processing unit (GPU). In medical image analysis, 3D image registration generally takes relatively long time, which is not feasible for clinical applications. To solve this problem, this paper proposed a high performance computational method based on CUDA, which took full advantage of GPU parallel computing under CUDA architecture combined with image multiple scale and maximum mutual information. Experiments showed that this algorithm can not only maintain the registration accuracy but also greatly increase the speed of registration process and meet the real-time requirement of clinical application. PMID- 24212004 TI - Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma. AB - Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity. PMID- 24212005 TI - Cytoplasm segmentation on cervical cell images using graph cut-based approach. AB - This paper proposes a method to segment the cytoplasm in cervical cell images using graph cut-based algorithm. First, the A* channel in CIE LAB color space is extracted for contrast enhancement. Then, in order to effectively extract cytoplasm boundaries when image histograms present non-bimodal distribution, Otsu multiple thresholding is performed on the contrast enhanced image to generate initial segments, based on which the segments are refined by the multi-way graph cut method. We use 21 cervical cell images with non-ideal imaging condition to evaluate cytoplasm segmentation performance. The proposed method achieved a 93% accuracy which outperformed state-of-the-art works. PMID- 24212006 TI - Cerebral activation and lateralization due to the cognition of a various driving speed difference: an fMRI study. AB - This study investigated the changes of cerebral activation and lateralization due to the cognition of three driving speeds in comparison to a reference driving speed using functional magnetic resonance imaging fMRI. A driving video as a visual stimulation source was recorded with four different driving speeds in a real driving situation. The experiment consisted of three blocks and each block included a one-minute control phase and a one-minute stimulation phase. The activation area and the lateralization index were analyzed by subtracting high speed data from low speed data. Such areas as occipital, parietal and frontal lobes, which is related to visual cognition, high order visual and spatial attention (or vigilance), were activated due to the cognition of various driving speed differences. As the driving speed difference increased, the activation area increased in the areas related to spatial attention (or vigilance), such as the frontal lobe, however, changes of neuronal activation in the occipital and parietal lobes were inconsistent. As the driving speed difference increased, the absolute value of cerebral lateralization decreased. These results may provide some basic data for elucidating the brain-function mechanism related to the cognition of a various driving speed difference based on a realistic visual stimulation. PMID- 24212007 TI - Human gastric cancer cell line SGC-7901 apoptosis induced by SFPS-B2 via a mitochondrial-mediated pathway. AB - This study was to investigate the effect of Sargassum fusiforme polysaccharides (SFPS-B2) on the proliferation and apoptosis of human gastric cancer cell line SGC-7901. Cells were treated with different concentrations of SFPS-B2. MTT and flow cytometry (FCM) assays were performed to evaluate the effect of SFPS-B2 on the cell growth and apoptosis. Inverted fluorescent microscope was used to observe cell morphology. Laser scanning confocal microscope (LSCM) was used to analyze intracellular calcium ion concentration, mitochondrion permeability transition pore (MPTP) and mitochondrial membrane potential (MMP). Spectrophotometer was applied to quantify the activity of Caspase-9 and Caspase 3. FCM was used to determine the expressions of Bcl-2, Bax and cytochrome C. It was shown that SFPS-B2 inhibited the growth of SGC-7901. After the treatment for 72 h, the cell apoptosis morphology was obvious, which showed that cell protuberance and apoptotic body appeared, and the cytoplasm was concentrated; the apoptotic peak appeared and the apoptotic rate increased in a dose-dependent manner. After the treatment for 24 h, SFPS-B2 activated intracellular MPTP and decreased MMP. It also increased the activity of Caspase-9 and Caspase-3, down regulated the expression of Bcl-2 and up-regulated the expression of Bax, induced the release of Cyt-C. SFPS-B2 induced SGC-7901 apoptosis through a mitochondrial mediated pathway, suggesting it may be an agent for cancer treatment. PMID- 24212008 TI - A non-rigid registration method for cerebral DSA images based on forward and inverse stretching - avoiding bilinear interpolation. AB - In order to reduce the motion artifact caused by the patient in cerebral DSA images, a non-rigid registration method based on stretching transformation is presented in this paper. Unlike other traditional methods, it does not need bilinear interpolation which is rather time-consuming and even produce 'originally non-existent gray value'. By this method, the mask image is rasterized to generate appropriate control points. The Energy of Histogram of Differences criterion is adopted as similarity measurement, and the Powell algorithm is utilized for acceleration. A forward stretching transformation is used to complete motion estimation and an inverse stretching transformation to generate target image by pixel mapping strategy. This method is effective to maintain the topological relationships of the gray value before and after the image deformation. The mask image remains clear and accurate contours, and the quality of the subtraction image after the registration is favorable. This method can provide support for clinical treatment and diagnosis of cerebral disease. PMID- 24212009 TI - Thermal computed tomography for biological tissue reconstruction based on radiation balance. AB - In this paper, a thermal computed tomography (TCT) for structural reconstruction of optical-thin biological tissues is proposed, which is based on a radiation balance between adjacent infinitesimals. A theoretical analysis has been carried out and several influential factors have been analyzed for the reconstructions of a physical model in numerical simulations. The simulation results give a criterion of how to choose an appropriate set of parameters to reconstruct biological tissues with the TCT. Besides, a TCT system was established and a validation experiment was carried out. The studies of both numerical simulations and experiments have verified the feasibility of the proposed TCT and give a valuable reference for the future applications of TCT in biology. PMID- 24212010 TI - Experimental exploration of mouse kidney imaging with the SR PCI technology. AB - This paper explores mouse kidney imaging with diffraction enhanced imaging (DEI) and inline outline X-ray imaging (IOXI) technology, and evaluates latent value of kidney imaging with phase contrast imaging technology. In our experiment, spatial resolution and tissue contrast serve as element evaluation and comparison. Images obtained from our experiment exhibit clearly observable contrasts and high resolution, suggesting X-RAY and IOXO are suitable for capturing kidney images. Also, further comparison shows IOXO has a better performance than DEI in capturing microstructures. PMID- 24212011 TI - Value of F-18 FDG PET/CT in detection and prognostication of isolated extra axillary lymph node recurrences in postoperative breast cancer. AB - We assessed the role of F-18 FDG PET/CT in evaluating isolated extra-axillary lymph node recurrences in postoperative breast cancer patients and its prognostic value on clinical outcome. We reviewed PET/CT scans of postoperative breast cancer patients performed at our institution between July 2003 and February 2012. We recorded PET/CT findings, clinicopathologic variables and treatment modalities. We analyzed metabolic parameters from PET/CT and clinicopathologic variables with respect to progression free survival (PFS). A total of 3561 PET/CT scans were performed in 1906 postoperative breast cancer patients with a median interval of 43 month from curative surgery. Fifty seven patients (2.99%) demonstrated isolated extra-axillary nodal recurrences (n=85) on PET/CT (internal mammary node recurrences in 28, supraclavicular 24, infraclavicular 4, interpectoral 8, cervical 12, and mediastinal 9).The median SUVmax was 7.8 (range, 1.8~19.0), and the median node size was 15 mm (range, 6~38 mm). All recurrences were nonpalpable. Based on PET/CT findings, 53 out of 57 patients with extra-axillary node recurrences underwent subsequent chemotherapy/radiation therapy. The estimated 3-year PFS rate was 48.6%. Cutoff points of SUVmax 2.7 and size 14 mm were the best discriminative values for predicting clinical outcome. SUVmax and size of extra-axillary nodal recurrences were significantly correlated to PFS on univariate and multivariate analyses (p<0.001 and p=0.019, respectively). PMID- 24212012 TI - Emotion recognition based on the sample entropy of EEG. AB - A sample entropy (SampEn)-based emotion recognition approach was presented. The SampEn results of notable EEG channels screened by K-S test were fed to the support vector machine (SVM)-weight classifier for training, after which it was applied to two emotion recognition tasks. One is to distinguish positive and negative emotion with high arousal and the other genitive emotion with different arousal status. Results showed that channels related to emotions were mostly located on the prefrontal region, i.e., F3, CP5, FP2, FZ, and FC2. And they were applied to form the input vectors of SVM-weight classifier. The accuracies of the present algorithm for the two tasks were 80.43% and 79.11%, respectively indicated by the leave-one-person-out validation procedure, demonstrating that the present algorithm had a reasonable generalization capability. PMID- 24212013 TI - Filter based receive-side spatial compounding for veterinary ultrasound B-mode imaging. AB - Veterinary ultrasound has been used in a large number of animal husbandry-related circumstances while many corresponding applications also call for the use of ultrasound in human patients. However, veterinary ultrasound images are affected by speckle, an interference pattern that can reduce the quality and contrast of ultrasound images. In this paper, a filter-based receive-side spatial compounding technique for veterinary ultrasound B-Mode imaging is used to create a compounded veterinary B-Mode image based on multiple looks. In particular, filtering in the lateral direction has been proved to be able to preserve the axial information in the sub-bands and to create decorrelation between sub-bands at the expense of some lateral resolution. A new method was proposed to obtain B-Mode IQ data by special veterinary ultrasonic probe. This approach is tested on 275 in-vivo swine. The effect is accomplished in real-time veterinary ultrasonic imaging with a measurable improvement of SNRe. Meanwhile, the speckle and electronic noise in the compounded image have been greatly reduced and smoothed in the visual result. PMID- 24212014 TI - Optimization of acoustic emitted field of transducer array for ultrasound imaging. AB - A method is proposed to calculate the weight vector of a transducer array for ultrasound imaging to obtain a low-sidelobe transmitting beam pattern based on the near-field response vector. An optimization problem is established, and the second-order cone (SOC) algorithm is used to solve the problem to obtain the weight vector. The optimized acoustic emitted field of the transducer array is then calculated using the Field II program by applying the obtained weight vector to the array. The simulation results with a 64-element 26 MHz linear phased array show that the proposed method can be used to control the sidelobe of the near field transmitting beam pattern of the transducer array and achieve a low sidelobe level. The near-field sound pressure distribution of the transducer array using the proposed method focuses much better than that using the standard delay and sum (DAS) beamforming method. The sound energy is more concentrated using the proposed method. PMID- 24212015 TI - Texture analysis and classification of ultrasound liver images. AB - Ultrasound as a noninvasive imaging technique is widely used to diagnose liver diseases. Texture analysis and classification of ultrasound liver images have become an important research topic across the world. In this study, GLGCM (Gray Level Gradient Co-Occurrence Matrix) was implemented for texture analysis of ultrasound liver images first, followed by the use of GLCM (Gray Level Co occurrence Matrix) at the second stage. Twenty two features were obtained using the two methods, and seven most powerful features were selected for classification using BP (Back Propagation) neural network. Fibrosis was divided into five stages (S0-S4) in this study. The classification accuracies of S0-S4 were 100%, 90%, 70%, 90% and 100%, respectively. PMID- 24212016 TI - Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma. AB - The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord. PMID- 24212017 TI - Matching of feature points based on TSSC method from MR images of nonrigid deformed tissues. AB - Due to the nonlinear and nonuniform local deformation of nonrigid tissues, it is difficult to match a number of feature points distributing somewhat uniform in the tissues from MR images for deformation measurement. This paper proposes TSSC (TPS-SURF-SAC-Clustering) based method of feature point matching and elimination of mismatching. First, Fast-Hessian and Harris operator are utilized to extract the feature points in the initial MR image, and the matching region is identified by TPS transformation model for every query point in the deformed image. Then the SURF descriptors and the proposed Spatial Association Correspondence (SAC) method are combined to match the feature points. Finally, by clustering the coordinate differences between the matching points obtained by TPS-SURF-SAC and the matching points calculated by TPS model, most incorrectly matched points are eliminated. After every iterative processing of matching and mismatching elimination, the updated TPS model becomes more accurate and more correctly so that the matched points can be identified than those of last iteration. The experimental results show that the proposed SAC was efficient and that TSSC based method outperformed the single SURF or SIFT method. PMID- 24212018 TI - Bias correction for magnetic resonance images via joint entropy regularization. AB - Due to the imperfections of the radio frequency (RF) coil or object-dependent electrodynamic interactions, magnetic resonance (MR) images often suffer from a smooth and biologically meaningless bias field, which causes severe troubles for subsequent processing and quantitative analysis. To effectively restore the original signal, this paper simultaneously exploits the spatial and gradient features of the corrupted MR images for bias correction via the joint entropy regularization. With both isotropic and anisotropic total variation (TV) considered, two nonparametric bias correction algorithms have been proposed, namely IsoTVBiasC and AniTVBiasC. These two methods have been applied to simulated images under various noise levels and bias field corruption and also tested on real MR data. The test results show that the proposed two methods can effectively remove the bias field and also present comparable performance compared to the state-of-the-art methods. PMID- 24212019 TI - Novel lattice Boltzmann method based on integrated edge and region information for medical image segmentation. AB - The lattice Boltzmann (LB) method is a mesoscopic method based on kinetic theory and statistical mechanics. The main advantage of the LB method is parallel computation, which increases the speed of calculation. In the past decade, LB methods have gradually been introduced for image processing, e.g., image segmentation. However, a major shortcoming of existing LB methods is that they can only be applied to the processing of medical images with intensity homogeneity. In practice, however, many medical images possess intensity inhomogeneity. In this study, we developed a novel LB method to integrate edge and region information for medical image segmentation. In contrast to other segmentation methods, we added edge information as a relaxing factor and used region information as a source term. The proposed method facilitates the segmentation of medical images with intensity inhomogeneity and it still allows parallel computation. Preliminary tests of the proposed method are presented in this paper. PMID- 24212020 TI - A statistical approach to segmentation of diffusion tensor imaging. AB - The aim of this study is to design a statistical segmentation technique to allow extraction of grey matter, white matter and cerebral spinal fluid volumes from diffusion tensor imaging. Four channel maps of the DTI are used as the input features, which provide more information for brain tissue segmentation compared with single channel map. An Improved Bayesian decision in the subspace spanned by the eigenvectors which are associated with the smaller eigenvalues in each class is adopted as the brain tissue segmentation criterion. Our method performed well, giving an average segmentation accuracy of about 0.88, 0.85 and 0.76 for white matter, gray matter and cerebrospinal fluid respectively in terms of volume overlap. PMID- 24212021 TI - Detection and measurement of fetal abdominal contour in ultrasound images via local phase information and iterative randomized Hough transform. AB - Due to the characteristic artifacts of ultrasound images, e.g., speckle noise, shadows and intensity inhomogeneity, traditional intensity-based methods usually have limited success on the segmentation of fetal abdominal contour. This paper presents a novel approach to detect and measure the abdominal contour from fetal ultrasound images in two steps. First, a local phase-based measure called multiscale feature asymmetry (MSFA) is de ned from the monogenic signal to detect the boundaries of fetal abdomen. The MSFA measure is intensity invariant and provides an absolute measurement for the signi cance of features in the image. Second, in order to detect the ellipse that ts to the abdominal contour, the iterative randomized Hough transform is employed to exclude the interferences of the inner boundaries, after which the detected ellipse gradually converges to the outer boundaries of the abdomen. Experimental results in clinical ultrasound images demonstrate the high agreement between our approach and manual approach on the measurement of abdominal circumference (mean sign difference is 0.42% and correlation coef cient is 0.9973), which indicates that the proposed approach can be used as a reliable and accurate tool for obstetrical care and diagnosis. PMID- 24212022 TI - Preparation and characterization of silicone rubber/nano-copper nanocomposites for use in intrauterine devices. AB - In this work, a novel silicone rubber/nano-copper nanocomposite for use in intrauterine devices (IUDs) was developed. Moreover, the release rate of Cu2+ ions and the water absorption of the prepared nanocomposite were investigated in detail. The results indicate that the release rate of Cu2+ ions and water absorption capability of the silicone rubber/nanocopper nanocomposite increase as the nano-copper content increases. SEM analysis suggested there is a uniform dispersion of nano-copper in the silicone matrix. Further, systematic analysis indicated that the release rate of Cu2+ ions in the prepared nanocomposite-based IUD can be stabilized for months, which is not possible in the case of traditional IUDs. PMID- 24212023 TI - Evaluation of the accuracy of a common regional registration method for three dimensional reconstruction of edentulous jaw relation by a 7-axis three dimensional measuring system. AB - This study was to design a method to quantitatively evaluate three-dimensional (3D) reconstruction accuracy of spatial relationship of dental models based on a 7-axis contact 3D measuring system, and to evaluate the accuracy of a common regional registration method for edentulous jaw relation reconstruction. 3D surface data of edentulous dental casts with 10 positioning cylinders and wax occlusion rims of five patients were obtained using a dental scanner. The jaw relation was reconstructed using the common regional registration in the Geomagic software. Measurements were obtained for line length, vertical distance and horizontal distance between centric points from two sources with upper jaw model base plane as a reference plane. The statistical description of measurement data was done. x +/- s of line length, vertical distance and horizontal distance between the center points of each data set were 0.107 +/- 0.354, 0.076 +/- 0.576 and 0.108 +/- 0.530 mm, respectively. Data was analyzed using the paired samples t-test and one-way analysis of variance. Paired t-test results of each patient and one-way analysis of variance for the five patients showed no significant differences (P>0.05). Using the Faro Edge system and standardized positioning cylinders, quantitative evaluation of the 3D reconstruction accuracy of edentulous jaw relation was workable. And results of common regional registration method met clinical requirements. PMID- 24212024 TI - A novel edge detection in medical images by fusing of multi-model from different spatial structure clues. AB - Edge detection has been widely used in medical image processing, automatic diagnosis, et al. A novel edge detection algorithm, based on the fusion model, is proposed by combination with the two proposed models as follows: the matrix of most probable distribution of edge point and the matrix of the difference weight of each point. The most probable distribution of edge point can be obtained by analyzing the variance among 4-connected neighborhood points around each pixel under estimation in the image to label the all candidate edge points in the image. The difference weight of each point can be gotten by analyzing the brightness difference between the neighborhood point and the under-estimating pixel to represent the probability of being edge. The two matrices gotten from the different descriptions of spatial structure are fused together and derive from the final edge image with thresholding method on the fusion matrix. The experiments are performed based on the public diabetic retinopathy database DRIVE. According to the edge images obtained, the proposed method is subjectively analyzed to be complete and close to the Ground Truth image with very low noise in comparison with the Sobel, Canny and LOG edge detectors. The F1 measure, ROC measure and PFOM measure are separately adopted to make quantitative evaluation of the proposed edge detection algorithm. Experimental results show that the proposed method is able to improve the effect of edge detection on medical images. PMID- 24212025 TI - Numerical analysis of the effect of T-tubule location on calcium transient in ventricular myocytes. AB - Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+, buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes. PMID- 24212026 TI - A granular computing approach to gene selection. AB - Gene selection is a key step in performing cancer classification with DNA microarrays. The challenges from high dimension and small sample size of microarray dataset still exist. On rough set theory applied to gene selection, many algorithms have been presented, but most are time-consuming. In this paper, a granular computing-based gene selection as a new method is proposed. First, some granular computing-based concepts are introduced and then some of their important properties are derived. The relationship between positive region-based reduct and granular space-based reduct is discussed. Then, a significance measure of feature is proposed to improve the efficiency and decrease the complexity of classical algorithm. By using Hashtable and input sequence techniques, a fast heuristic algorithm is constructed for the better computational efficiency of gene selection for cancer classification. Extensive experiments are conducted on five public gene expression data sets and seven data sets from UCI respectively. The experimental results confirm the efficiency and effectiveness of the proposed algorithm. PMID- 24212027 TI - A combination of pharmacophore modeling, molecular docking and virtual screening for iNOS inhibitors from Chinese herbs. AB - Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover new iNOS inhibitors. This study was performed to identify natural iNOS inhibitors from traditional Chinese herbs through a combination of pharmacophore modeling, molecular docking and virtual screening. First, the pharmacophore models were generated though six known iNOS inhibitors and validated by a test database. The pharmacophore model_017 showed good performance in external validation and was employed to screen Traditional Chinese Medicine Database (Version 2009), which resulting in a hit list of 498 compounds with matching score (QFIT) above 40. Then, the hits were subjected to molecular docking for further refinement. An empirical scoring function was used to evaluate the affinity of the compounds and the target protein. Parts of compounds with high docking scores have been reported to have the related pharmacological activity from the literatures. The results provide a set of useful guidelines for the rational discovery of natural iNOS inhibitors from Chinese herbs. PMID- 24212028 TI - An ensemble self-training protein interaction article classifier. AB - Protein-protein interaction (PPI) is essential to understand the fundamental processes governing cell biology. The mining and curation of PPI knowledge are critical for analyzing proteomics data. Hence it is desired to classify articles PPI-related or not automatically. In order to build interaction article classification systems, an annotated corpus is needed. However, it is usually the case that only a small number of labeled articles can be obtained manually. Meanwhile, a large number of unlabeled articles are available. By combining ensemble learning and semi-supervised self-training, an ensemble self-training interaction classifier called EST_IACer is designed to classify PPI-related articles based on a small number of labeled articles and a large number of unlabeled articles. A biological background based feature weighting strategy is extended using the category information from both labeled and unlabeled data. Moreover, a heuristic constraint is put forward to select optimal instances from unlabeled data to improve the performance further. Experiment results show that the EST_IACer can classify the PPI related articles effectively and efficiently. PMID- 24212029 TI - Mechanism of action of salvianolic acid B by module-based network analysis. AB - Salvianolic Acid B (Sal B) is one of the main medicinal ingredients of Radix Salvia miltiorrhiza (Danshen) and possesses a variety of pharmacological effects. The purpose of this study was to discover the new mechanism of action of Sal B based on the protein interaction network (PIN) analysis. A PIN of Sal B was constructed with 852 nodes and 8,626 interactions. By fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC), 11 modules were detected from the network. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of Sal B played in cardiovascular disease were related to multiple biological processes, which could represent the characteristics of Chinese Material Medica (CMM) as a whole to regulate the disease. The most interesting finding of this work was that the anti-inflammatory effect of Sal B was due to the immune response of T lymphocytes by regulating IL-2 family, CD3E, CD79A, MAP3K7 and PRKCQ. Therefore, the module-based network analysis will be an effective method for better understanding CMM. PMID- 24212030 TI - Mouse coronary angiography in vivo using synchrotron radiation. AB - PURPOSE: To establish a method for mouse coronary angiography in vivo using synchrotron radiation, which is essential for physiological and pathological research on coronary diseases. METHODS: 1) The imaging parameters (e.g., photon energy, spatial resolution of the detector, and injection rate of contrast agent) optimal for the quality of acquired images in a simulation were determined. 2) Through animal experiments, the effectiveness of these optimal parameters and the repeatability of in vivo coronary angiography were verified. 3) An algorithm for background subtraction and contrast enhancement was designed and employed to compensate for the effects of interference and the effective information extracted used for diagnosing coronary disease. RESULTS AND CONCLUSIONS: An optimal set of the imaging parameters was finally determined: photon energy of 33 34 keV, detector's spatial resolution of 30 MUm or higher, image capture rate of 20 f/s or more, concentration of lopamidol solution of 75% as contrast agent and a pulse injection of contrast agent at a high rate. PMID- 24212031 TI - GPU accelerating technique for rendering implicitly represented vasculatures. AB - With the flooding datasets of medical Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), implicit modeling techniques are increasingly applied to reconstruct the human organs, especially the vasculature. However, displaying implicitly represented geometric objects arises heavy computational burden. In this study, a Graphics Processing Unit (GPU) accelerating technique was developed for high performance rendering of implicitly represented objects, especially the vasculatures. The experimental results suggested that the rendering performance was greatly enhanced via exploiting the advantages of modern GPUs. PMID- 24212032 TI - Quantitative influence of risk factors on blood glucose level. AB - The aim of this study is to quantitatively analyze the influence of risk factors on the blood glucose level, and to provide theory basis for understanding the characteristics of blood glucose change and confirming the intervention index for type 2 diabetes. The quantitative method is proposed to analyze the influence of risk factors on blood glucose using back propagation (BP) neural network. Ten risk factors are screened first. Then the cohort is divided into nine groups by gender and age. According to the minimum error principle, nine BP models are trained respectively. The quantitative values of the influence of different risk factors on the blood glucose change can be obtained by sensitivity calculation. The experiment results indicate that weight is the leading cause of blood glucose change (0.2449). The second factors are cholesterol, age and triglyceride. The total ratio of these four factors reaches to 77% of the nine screened risk factors. And the sensitivity sequences can provide judgment method for individual intervention. This method can be applied to risk factors quantitative analysis of other diseases and potentially used for clinical practitioners to identify high risk populations for type 2 diabetes as well as other disease. PMID- 24212033 TI - A method of semi-quantifying beta-AP in brain PET-CT 11C-PiB images. AB - Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-beta peptide, beta-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi quantify beta-AP. This paper proposes such a standardized value: SVbeta-AP. This standardized value measures the mean ratio between the dimension of beta-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVbeta-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVbeta-AP. The experiment results showed that it is technically feasible. PMID- 24212035 TI - Novel and efficient tag SNPs selection algorithms. AB - SNPs are the most abundant forms of genetic variations amongst species; the association studies between complex diseases and SNPs or haplotypes have received great attention. However, these studies are restricted by the cost of genotyping all SNPs; thus, it is necessary to find smaller subsets, or tag SNPs, representing the rest of the SNPs. In fact, the existing tag SNP selection algorithms are notoriously time-consuming. An efficient algorithm for tag SNP selection was presented, which was applied to analyze the HapMap YRI data. The experimental results show that the proposed algorithm can achieve better performance than the existing tag SNP selection algorithms; in most cases, this proposed algorithm is at least ten times faster than the existing methods. In many cases, when the redundant ratio of the block is high, the proposed algorithm can even be thousands times faster than the previously known methods. Tools and web services for haplotype block analysis integrated by hadoop MapReduce framework are also developed using the proposed algorithm as computation kernels. PMID- 24212034 TI - The effect of the material property change of anterior cruciate ligament by ageing on joint kinematics and biomechanics under tibial varus/valgus torques. AB - It is known that the anterior cruciate ligament (ACL) plays a role in providing joint stabilities under tibial varus/valgus torques and the material behavior of the ACL has changed with ageing. However, the effect of this variation of the ACL material property on joint kinematics and biomechanics under tibial varus/valgus torques has still not been clarified.In this paper, three finite element (FE) models of an intact tibiofemoral joint were reconstructed with different ACL material properties, corresponding to the ACL on the younger, middle and older ages, respectively. The joint kinematics, the stress distribution and resultant force of the ACL were obtained under a tibial varus or valgus torque load. It was found that the variation in the ACL material property would result in great changes in some joint displacements (i.e., the tibial anterior translation and external rotation). The maximal stress value in the ACL had also altered while the stress distribution did not varied obviously. The great change in the tibial anterior translation illustrated that ACL played an important role against varus/valgus torques by controlling the coupled tibial anterior translation//external rotation rather than the corresponding varus/valgus rotation. PMID- 24212036 TI - Biochemical kinetics of cell proliferation regulated by extremely low frequency electromagnetic field. AB - To study the mechanism of cells subjected to external electromagnetic fields, the expression of cyclin kinase inhibitor p27 is analyzed in the four cell cycle phases. The regulatory functions are investigated in gap phase1 to synthesis, gap phase 2 to mitotic phase and post mitotic phase transition in the mammalian cell cycle processes. A mathematical model is developed to meet the general cell cycle regulatory network based on the molecular dynamics method. Phase plane analysis results show that the p27 over-expression can lead to the hysteresis effect of cell cycle processes and phase transition delay. It is an universal approach to predict the key regulatory gene in signal transduction pathway. PMID- 24212037 TI - Tumor classification based on orthogonal linear discriminant analysis. AB - Gene expression profiles have great potential for accurate tumor diagnosis. It is expected to enable us to diagnose tumors precisely and systematically, and also bring the researchers of machine learning two challenges, the curse of dimensionality and the small sample size problems. We propose a manifold learning based dimensional reduction algorithm named orthogonal local discriminant embedding (O-LDE) and apply it to tumor classification. Comparing with the classical local discriminant embedding (LDE), O-LDE aims to obtain an orthogonal linear projection matrix by solving an optimization problem. After being projected into a low-dimensional subspace by O-LDE, the data points of the same class maintain their intrinsic neighbor relations, whereas the neighboring points of the different classes are far from each other. Experimental results on a public tumor dataset validate the effectiveness and feasibility of the proposed algorithm. PMID- 24212038 TI - Finite element analysis of dental implant neck effects on primary stability and osseointegration in a type IV bone mandible. AB - The purpose of this study is to investigate the effect of implant neck design and cortical bone thickness by means of 3-D linearly elastic finite element analysis and to analyze primary and secondary stability of clinical evidence based on micromotion and principal stress. Four commercial dental implants, comparable in size, for a type IV bone and mandibular segments were created. Various parameters were considered, including the osseointegration condition (non- and full bonded), force direction (vertical and horizontal) and cortical bone thickness (0.3, 0.5 and 1mm). The force was considered a static load applied at the top of the platform. The magnitudes of the vertical and horizontal loading direction were 500 N and 250 N. Micromotion and principal stresses were employed to evaluate the failure of osseointegration and bone overloading, respectively. The results show that Maximum stress of the peri-implant bone decreased as cortical bone thickness increased. The stress concentration regions were located at the implant neck between the cortical bone and cancellous bone. The micromotion level in full osseointegration is less than that in non-osseointegration and it also decreases as a increasing of cortical bone thickness. Consequently, cortical bone thickness is a key factor for primary stability. PMID- 24212039 TI - Parallel acceleration for modeling of calcium dynamics in cardiac myocytes. AB - Spatial-temporal calcium dynamics due to calcium release, buffering, and re uptaking plays a central role in studying excitation-contraction (E-C) coupling in both healthy and defected cardiac myocytes. In our previous work, partial differential equations (PDEs) had been used to simulate calcium dynamics with realistic geometries extracted from electron microscopic imaging data. However, the computational costs of such simulations are very high on a single processor. To alleviate this problem, we have accelerated the numerical simulations of calcium dynamics by using graphics processing units (GPUs). Computational performance and simulation accuracy are compared with those based on a single CPU and another popular parallel computing technique, OpenMP. PMID- 24212040 TI - [From the 4th Interdisciplinary Conference of Orvosi Hetilap]. PMID- 24212041 TI - [Trends in the utilization of food additives]. AB - The frequent media reports on food additives weakened consumers' trust in food producers and food control authorities as well. Furthermore, consumers' uncertainty is also raised by the fact that they obtain their information from inadequate, mistrustful sources and, therefore, consumers might avoid the consumption of certain foodstuffs. While food producers may react by replacing artificial components by natural ones, they try to emphasize the favourable characteristics of their products. The authors describe the main trends and efforts related to food additives. On the basis of the overview it can be concluded that - besides taking into consideration consumers' needs - product development and research directions are promising. Food producers' efforts may help to restore consumer confidence and trust and they may help them to have informed choice. PMID- 24212042 TI - [Vitamin D level in Hungarian patients with inflammatory bowel diseases]. AB - INTRODUCTION: Vitamin D has an important role in the immune regulation. Vitamin D is essential for innate and adaptive immune systems and it plays a significant role in the formation of immune tolerance, as well. AIM: Vitamin D deficiency has been observed in patients with inflammatory bowel diseases in Western Europe, but there is no data available from Eastern Europe. METHOD: The study included 169 patients with inflammatory bowel disease. RESULTS: The median vitamin D level was 22.7+/-10.6 ng/ml. Only 20% of the patients had adequate vitamin D level (>30 ng/ml), 52% had vitamin D insufficiency (15-30 ng/ml), and 28% of them had severe vitamin D deficiency (<15 ng/ml). Vitamin D concentration failed to correlate with clinical activity indexes (partial Mayo score: r = -0.143; Crohn's disease activity index: r = -0.253) and with inflammatory parameters (C-reactive protein: r = 0.008; erythrocyte sedimentation rate: r = 0.012). CONCLUSIONS: Since vitamin D deficiency can be frequently observed in Hungarian patients with inflammatory bowel disease, its level should be tested in these patients. PMID- 24212044 TI - [Cryptosporidium and Giardia as water contaminant pathogens in Hungary]. AB - INTRODUCTION: Many species of Cryptosporidium, and two assemlages of Giardia duodenalis cause typically acute diaorrhoea in human. The oocysts and cysts of these parasites excreted in faeces are capable of infecting other hosts and those are environmentally stable. AIM: The aims of the study were to evaluate the prevalence and genotypes of Cryptosporidium and Giardia species from different water sources as well as to monitor and characterize the (oo)cyst contamination sources in watersheds. In addition, an epidemiological study was performed in three selected settlements. METHOD: Wide range of modern epidemiological and molecular detection methods have been applied. RESULTS: (Oo)cysts densities were associated with water receiving effluents of sewage treatment plants or originating from a forest environment. It was confirmed, that cattle can be a source of Cryptosporidium oocysts at watersheds and aquatic birds can play a role in the environmental dissemination of these protozoa. The epidemiological study demonstrated a specific epidemiological situation, giving essential evidence about giardiasis in asymptomatic carriers. The applied novel detection technology was found to be cost effective and simple procedure for screening catchments to identify those that require further treatment and more detailed microscopic counts. CONCLUSIONS: The presented results contribute to a better understanding the epidemiology and relevance of waterborne parasites, their surveillance and performance of future control measures to prevent waterborne infections in Hungary. PMID- 24212043 TI - [Hemorrhagic complications of chronic anticoagulant treatment in a single intensive care unit]. AB - INTRODUCTION: There are well defined indications in which chronic anticoagulant treatment has been widely applied. However, complications of this therapy are less discussed, although these complications may lead to serious or even fatal consequences. AIM: The aim of the authors was to analyze data of patients admitted to their multidisciplinary intensive care unit for complications of chronic anticoagulant therapy between January 1, 2006 and December 31, 2011. METHOD: Data of 73 patients admitted for serious hemorrhagic complications of chronic anticoagulant therapy were retrospectively analysed. RESULTS: Of the 73 patients, 63 patients had intracranial bleeding, most of them with traumatic origin. A few patients with other hemorrhagic complications such as spinal hematoma, gastrointestinal bleeding, hemorrhagic cystitis, hemothorax and intraabdominal bleeding were also noted. The INR values were out of therapeutic range in 43 patients. The mortality of patients was very high in spite of complex intensive care; 49 of the 73 patients (75.5%) died due to hemorrhagic complications. CONCLUSIONS: Due to the high proportion of traumatic origin, the large number of out-of-range INR, and the high mortality, the authors strongly believe that regular patient follow-up, transmission of detailed information, and time-to-time reevaluation of the indications and contraindications of chronic anticoagulant therapy could help to decrease the number of serious and fatal complications of chronic anticoagulant therapy. PMID- 24212045 TI - [Impact of attachment to God and religious coping on life satisfaction]. AB - INTRODUCTION: Effects of religiosity on satisfaction with life, mental and physical health are highly favored topics of psychology. At the same time, less attention has been directed to how individual differences in religiosity affect believers' satisfaction with life. AIM: The aim of this study was to investigate the relationship between attachment to God, religious coping and satisfaction with life. METHOD: A group of Roman Catholics (n = 94; 49 women and 45 men; age, 30.8+/-6.2 years) filled in our the survey package. The survey package contained the following measures: Attachment to God Inventory, Brief Religious Coping Scale, and Satisfaction with Life Scale. RESULTS: Negative religious coping and anxious attachment to God predicted lower satisfaction with life, even if demographic variables were controlled for. CONCLUSIONS: These results indicate that negative image of God is an important predictor of low satisfaction with life, which in turn can have negative impact on believers' mental and physical health. Orv. Hetil., 154(46), 1843-1847. PMID- 24212048 TI - Understanding the sources and fate of nitrate in a highly developed aquifer system. AB - Understanding the processes affecting the transport and fate of nitrate in coastal aquifers has become of great interest in recent years due to concerns of nutrient loading to coastal waters. Novel dual isotopic methods have shown promise for identifying sources and fate of nitrate in shallow groundwater. However, in relatively deep dynamic aquifer systems, the isotopic signatures may be overprinted by mixing of different end-member waters and biogeochemical processes. In this study, delta(15)N and delta(18)O of groundwater nitrate are coupled with other forensic geochemistry methods such as Cl/Br, SO4/Cl, and Cl/NO3 mass ratios and land use analysis in order to constrain the isotope correlations and better understand contaminant sources and biogeochemical processes. Most delta(15)NNO3 values were within ranges expected for nitrate formed by ammonia nitrification in soil. Furthermore, the persistent presence of nitrate in concentrations above background levels (median 2.3 mg/L) and the relatively low delta(15)NNO3 and delta(18)ONO3 (median: 4.5+/-0.20/00 AIR and 5.2+/-0.50/00 VSMOW, respectively) indicate no direct evidence of denitrification. However, denitrification was inferred for a few samples whereby more enriched delta(15)NNO3 and delta(18)ONO3 values coupled with an increase in SO4/Cl and Cl/NO3 ratios were observed. Finally, mixing trends were identified for a few of the samples as indicated by delta(15)NO3 and delta(18)ONO3 mixing ratios and were consistent with the study area's land-use/land-cover distribution. The combination of methods utilized in this study revealed that in some cases mass ratios were better diagnostics in elucidating the impact of denitrification, mixing processes, and source identification within dynamic aquifer systems than the dual-isotope technique. PMID- 24212047 TI - Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons. AB - Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca(2+) imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca(2+) imaging revealed that brief application (15-30 s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20 min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35 MUl) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents. PMID- 24212049 TI - Continuous time random walk in homogeneous porous media. AB - Continuous time random walk (CTRW) has been successfully applied in the description of anomalous transport in porous media in recent years. We simulate solute transport in randomly packed spheres with the same diameter and use CTRW to analyze the simulated results. From analysis, we find that there exists weak anomalous transport in the approximately homogeneous porous media. The anomaly becomes more apparent with the increase of Pe. This conclusion consists with previous simulations in two-dimensional homogeneous media and experimental data. We also calculate the trapping probabilities of solute particles in stagnant regions, which could give a physically based explanation for this non-Gaussian behavior. PMID- 24212050 TI - Left hemisphere fractional anisotropy increase in noise-induced tinnitus: a diffusion tensor imaging (DTI) study of white matter tracts in the brain. AB - Diffusion tensor imaging (DTI) is a contemporary neuroimaging modality used to study connectivity patterns and microstructure of white matter tracts in the brain. The use of DTI in the study of tinnitus is a relatively unexplored methodology with no studies focusing specifically on tinnitus induced by noise exposure. In this investigation, participants were two groups of adults matched for etiology, age, and degree of peripheral hearing loss, but differed by the presence or absence (+/-) of tinnitus. It is assumed that matching individuals on the basis of peripheral hearing loss, allows for differentiating changes in white matter microstructure due to hearing loss from changes due to the effects of chronic tinnitus. Alterations in white matter tracts, using the fractional anisotropy (FA) metric, which measures directional diffusion of water, were quantified using tract-based spatial statistics (TBSS) with additional details provided by in vivo probabilistic tractography. Our results indicate that 10 voxel clusters differentiated the two groups, including 9 with higher FA in the group with tinnitus. A decrease in FA was found for a single cluster in the group with tinnitus. However, seven of the 9 clusters with higher FA were in left hemisphere thalamic, frontal, and parietal white matter. These foci were localized to the anterior thalamic radiations and the inferior and superior longitudinal fasciculi. The two right-sided clusters with increased FA were located in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus. The only decrease in FA for the tinnitus-positive group was found in the superior longitudinal fasciculus of the left parietal lobe. PMID- 24212052 TI - Recent advances in cortisol sensing technologies for point-of-care application. AB - Everyday lifestyle related issues are the main cause of psychological stress, which contributes to health disparities experienced by individuals. Prolonged exposure to stress leads to the activation of signaling pathways from the brain that leads to release of cortisol from the adrenal cortex. Various biomarkers have been affected by psychological stress, but cortisol "a steroid hormone" is known as a potential biomarker for its estimation. Cortisol can also be used as a target analyte marker to determine the effect of exposure such as organophosphates on central nervous system, which alters the endocrine system, leading to imbalance in cortisol secretion. Cortisol secretion of individuals depends on day-night cycle and field environment hence its detection at point-of care (POC) is deemed essential to provide personalized healthcare. Chromatographic techniques have been traditionally used to detect cortisol. The issues relating to assay formation, system complexity, and multistep extraction/purification limits its application in the field. In order to overcome these issues and to make portable and effective miniaturized platform, various immunoassays sensing strategies are being explored. However, electrochemical immunosensing of cortisol is considered as a recent advancement towards POC application. Highly sensitive, label-free and selective cortisol immunosensor based on microelectrodes are being integrated with the microfluidic system for automated diurnal cortisol monitoring useful for personalized healthcare. Although the reported sensing devices for cortisol detection may have a great scope to improve portability, electronic designing, performance of the integrated sensor, data safety and lifetime for point-of-care applications, This review is an attempt to describe the various cortisol sensing platforms and their potential to be integrated into a wearable system for online and continuous monitoring of cortisol rhythm at POC as a function of one's environment. PMID- 24212051 TI - Evaluating capture stress in wild gray mouse lemurs via repeated fecal sampling: method validation and the influence of prior experience and handling protocols on stress responses. AB - Reliable measurements of physiological stress are increasingly needed for eco physiological research and for species conservation or management. Stress can be estimated by quantifying plasma glucocorticoid levels, but when this is not feasible, glucocorticoid metabolites are often measured from feces (FGCM). However, evidence is accumulating on the sensitivity of FGCM measurements to various nuisance factors. Careful species- and context-specific validations are therefore necessary to confirm the biological relevance and specificity of the method. The goals of this study were to: (1) establish and validate sampling methods and an enzymeimmunoassay to measure FGCM in the gray mouse lemur (Microcebus murinus); (2) explore causes of variability in the FGCM measurements, and; (3) assess the consequences of capturing and handling for free-living individuals by quantifying their stress responses via repeated fecal sampling within capture sessions. We further assessed the influence of different handling protocols and the animals' previous capture experience on the magnitude of the physiological response. Our validations identified the group-specific measurement of 11beta-hydroxyetiocholanolone as the most suitable assay for monitoring adrenocortical activity. The sample water content and the animal's age were found to significantly influence baseline FGCM-levels. Most captured animals exhibited a post-capture FGCM-elevation but its magnitude was not related to the handling protocol or capture experience. We found no evidence for long-term consequences of routine capturing on the animals' stress physiology. Hence the described methods can be employed to measure physiological stress in mouse lemurs in an effective and relatively non-invasive way. PMID- 24212053 TI - Reductive activation in periplasmic nitrate reductase involves chemical modifications of the Mo-cofactor beyond the first coordination sphere of the metal ion. AB - In Rhodobacter sphaeroides periplasmic nitrate reductase NapAB, the major Mo(V) form (the "high g" species) in air-purified samples is inactive and requires reduction to irreversibly convert into a catalytically competent form (Fourmond et al., J. Phys. Chem., 2008). In the present work, we study the kinetics of the activation process by combining EPR spectroscopy and direct electrochemistry. Upon reduction, the Mo (V) "high g" resting EPR signal slowly decays while the other redox centers of the protein are rapidly reduced, which we interpret as a slow and gated (or coupled) intramolecular electron transfer between the [4Fe-4S] center and the Mo cofactor in the inactive enzyme. Besides, we detect spin-spin interactions between the Mo(V) ion and the [4Fe-4S](1+) cluster which are modified upon activation of the enzyme, while the EPR signatures associated to the Mo cofactor remain almost unchanged. This shows that the activation process, which modifies the exchange coupling pathway between the Mo and the [4Fe-4S](1+) centers, occurs further away than in the first coordination sphere of the Mo ion. Relying on structural data and studies on Mo-pyranopterin and models, we propose a molecular mechanism of activation which involves the pyranopterin moiety of the molybdenum cofactor that is proximal to the [4Fe-4S] cluster. The mechanism implies both the cyclization of the pyran ring and the reduction of the oxidized pterin to give the competent tricyclic tetrahydropyranopterin form. PMID- 24212054 TI - Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation. AB - Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. PMID- 24212055 TI - Channelrhodopsin unchained: structure and mechanism of a light-gated cation channel. AB - The new and vibrant field of optogenetics was founded by the seminal discovery of channelrhodopsin, the first light-gated cation channel. Despite the numerous applications that have revolutionised neurophysiology, the functional mechanism is far from understood on the molecular level. An arsenal of biophysical techniques has been established in the last decades of research on microbial rhodopsins. However, application of these techniques is hampered by the duration and the complexity of the photoreaction of channelrhodopsin compared with other microbial rhodopsins. A particular interest in resolving the molecular mechanism lies in the structural changes that lead to channel opening and closure. Here, we review the current structural and mechanistic knowledge that has been accomplished by integrating the static structure provided by X-ray crystallography and electron microscopy with time-resolved spectroscopic and electrophysiological techniques. The dynamical reactions of the chromophore are effectively coupled to structural changes of the protein, as shown by ultrafast spectroscopy. The hierarchical sequence of structural changes in the protein backbone that spans the time range from 10(-12)s to 10(-3)s prepares the channel to open and, consequently, cations can pass. Proton transfer reactions that are associated with channel gating have been resolved. In particular, glutamate 253 and aspartic acid 156 were identified as proton acceptor and donor to the retinal Schiff base. The reprotonation of the latter is the critical determinant for channel closure. The proton pathway that eventually leads to proton pumping is also discussed. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks. PMID- 24212056 TI - Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition. AB - The age of acquisition (AoA) of objects and their names is a powerful determinant of processing speed in adulthood, with early-acquired objects being recognized and named faster than late-acquired objects. Previous research using fMRI (Ellis et al., 2006. Traces of vocabulary acquisition in the brain: evidence from covert object naming. NeuroImage 33, 958-968) found that AoA modulated the strength of BOLD responses in both occipital and left anterior temporal cortex during object naming. We used magnetoencephalography (MEG) to explore in more detail the nature of the influence of AoA on activity in those two regions. Covert object naming recruited a network within the left hemisphere that is familiar from previous research, including visual, left occipito-temporal, anterior temporal and inferior frontal regions. Region of interest (ROI) analyses found that occipital cortex generated a rapid evoked response (~75-200 ms at 0-40 Hz) that peaked at 95 ms but was not modulated by AoA. That response was followed by a complex of later occipital responses that extended from ~300 to 850 ms and were stronger to early- than late-acquired items from ~325 to 675 ms at 10-20 Hz in the induced rather than the evoked component. Left anterior temporal cortex showed an evoked response that occurred significantly later than the first occipital response (~100-400 ms at 0-10 Hz with a peak at 191 ms) and was stronger to early- than late-acquired items from ~100 to 300 ms at 2-12 Hz. A later anterior temporal response from ~550 to 1050 ms at 5-20 Hz was not modulated by AoA. The results indicate that the initial analysis of object forms in visual cortex is not influenced by AoA. A fastforward sweep of activation from occipital and left anterior temporal cortex then results in stronger activation of semantic representations for early- than late-acquired objects. Top-down re-activation of occipital cortex by semantic representations is then greater for early than late acquired objects resulting in delayed modulation of the visual response. PMID- 24212057 TI - Novel TASK channels inhibitors derived from dihydropyrrolo[2,1-a]isoquinoline. AB - TASK channels belong to the family of K(+) channels with 4 transmembrane segments and 2 pore domains (4TM/2P) per subunit. These channels have been related to apoptosis in cerebellar granule neurons (CGN), as well as cancer in other tissues. TASK current is regulated by hormones, neurotransmitters, anesthetics and divalent cations, which are not selective. Recently, there has been found some organic compounds that inhibit TASK current selectively. In order to find other modulators, we report here a group of five dihydropyrrolo[2,1 a]isoquinolines (DPIs), four of them with putative anticancer activity, that were evaluated on TASK-1 and TASK-3 channels. The compounds 1, 2 and 3 showed IC50 < 320 MUM on TASK-1 and TASK-3, intermediate activity on TASK-1/TASK-3 heterodimer, moderate effect over hslo and TREK-1 (500 MUM), and practically not inhibition on Shaker-IR, herg and IRK2.1 potassium channels, when they were expressed heterologously in Xenopus laevis oocytes. In rat CGN, 500 MUM of these three compounds induced a decrement by >39% of the TASK-carried leak current. Finally, only compound 1 showed significant protection (~36%) against apoptotic death of CGN induced by K(+) deprivation. These results suggest that DPI compounds could be potential candidates for designing new selective inhibitors of TASK channels. PMID- 24212059 TI - Recombinant human thioredoxin-1 promotes neurogenesis and facilitates cognitive recovery following cerebral ischemia in mice. AB - Cerebral ischemia (CI) can induce loss of hippocampal neurons, causing cognitive dysfunction such as learning and memory deficits. In adult mammals, the hippocampal dentate gyrus contains neural stem cells (NSCs) that continuously generate newborn neurons and integrate into the pre-existing networks throughout life, which may ameliorate cognitive dysfunction following CI. Recent studies have demonstrated that recombinant human thioredoxin-1 (rhTrx-1) could promote proliferation of human adipose tissue-derived mesenchymal stem cells and angiogenesis. To investigate whether rhTrx-1 also regulates hippocampal neurogenesis following CI and its underlying mechanisms, adult mice were subjected to bilateral common carotid arteries occlusion (BCCAO) to induce CI and treated with rhTrx-1 before reperfusion. Mice treated with rhTrx-1 showed shortened escape latencies in Morris water maze by 30 days and improvements in spatial memory demonstrated by probe trial test. Enhanced NSCs proliferation was observed at day 14, indicated by BrdU and Ki67 immunostaining. Doublecortin (DCX)(+) cells were also significantly increased following rhTrx-1 treatment. Despite increases in BrdU(+)/NeuN(+) cells by day 30, the double-labeling to total BrdU(+) ratio was not affected by rhTrx-1 treatment. The promotive effects of rhTrx-1 on NSCs proliferation and differentiation were further confirmed in in vitro assays. Western blot revealed increased ERK1/2 phosphorylation after rhTrx 1 treatment, and the ERK inhibitor U0126 abrogated the effects of rhTrx-1 on NSCs proliferation. These results provide initial evidence that rhTrx-1 effects neurogenesis through the ERK signaling pathway and are beneficial for improving spatial learning and memory in adult mice following global CI. PMID- 24212058 TI - Presynaptic adenosine A1 receptors modulate excitatory transmission in the rat basolateral amygdala. AB - The basolateral amygdala (BLA) plays an integral role in the etiology of anxiety disorders and alcoholism. Although much is known about the intrinsic circuitry that governs BLA excitability, our understanding of the neuromodulators that control BLA excitation is incomplete. In many brain regions, adenosine (ADO) regulates neuronal excitability, primarily via A1 receptor inhibition of glutamate release, and basal adenosinergic tone is high enough to tonically inhibit neuronal excitation. Although ADO signaling modulates many anxiety- and alcohol-related behaviors, little is known about ADO regulation of BLA neurotransmission. To that end, we used patch clamp methods in rodent brain slices to characterize adenosinergic modulation of excitatory neurotransmission onto BLA pyramidal cells. ADO significantly inhibited EPSCs evoked by stimulation of either medial or external glutamatergic inputs into the BLA. This effect was mimicked by an A1, but not by an A(2a), agonist. Paired-pulse ratio and miniature EPSC experiments revealed that A1 receptors reside at a presynaptic locus on BLA glutamatergic synapses. Moreover, bath application of an A1 receptor antagonist significantly enhanced EPSCs, providing evidence of tonic adenosinergic tone at BLA glutamatergic synapses. In addition, tonic ADO was regulated by adenosine kinase, but not adenosine deaminase. Finally, activation of A1 receptors had no direct effects on the intrinsic excitability of BLA pyramidal cells. Collectively, these data suggest that tonic A1 receptor signaling may play an important role in regulating BLA excitability and suggest a possible neurobiological substrate through which ADO may contribute to the pathophysiology of anxiety disorders and alcohol addiction. PMID- 24212060 TI - High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress like response. AB - The hypothalamic-pituitary-adrenal (HPA) axis is activated by a wide range of stimuli, including drugs. Here we report that in male rats, a dose of sodium butyrate (NaBu) that is typically used to inhibit histone deacetylation (1200 mg/kg) increased the peripheral levels of HPA hormones and glucose. In a further experiment, we compared the effects of two different doses of NaBu (200 and 1200 mg/kg) and equimolar saline solutions on peripheral neuroendocrine markers and brain c-Fos expression to demonstrate a specific stress-like effect of NaBu that is not related to hypertonicity and to localise putatively involved brain areas. Only the high dose of NaBu increased the plasma levels of stress markers. The equimolar (hypertonic) saline solution also activated the HPA axis and the c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN), a key area for the control of the HPA axis, but the effects were of a lower magnitude than those of NaBu. Regarding other brain areas, group differences in c-Fos expression were not observed in the medial prefrontal cortex or the medial amygdala, but they were observed in the central amygdala and the lateral ventral septum. However, only the latter area of the NaBu group showed enhanced c-Fos expression that was significantly higher than that after hypertonic saline. The present data indicate that high doses of NaBu appear to act as a pharmacological stressor, and this fact should be taken into account when using this drug to study the role of epigenetic processes in learning and emotional behaviour. PMID- 24212061 TI - Effectiveness of a primary care practice intervention for increasing colorectal cancer screening in Appalachian Kentucky. AB - OBJECTIVE: This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. METHODS: Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. RESULTS: A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). CONCLUSIONS: Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy. PMID- 24212062 TI - Roles of Th17 cells in pulmonary granulomas induced by Schistosoma japonicum in C57BL/6 mice. AB - In schistosomiasis, limited information is available about the role of interleukin-17 (IL-17) in lung, despite the fact that this cytokine plays a crucial role during pro-inflammatory immune responses. In our study, we observed CD4(+)T cells changed after the infection. Furthermore, ELISA and FACS results revealed that Schistosomajaponicum infection could induce a large amount of IL-17 in mouse pulmonary lymphocytes. IL-17-producing cells, including Th17 cells, CD8(+)T (Tc) cells, gammadeltaT cells and natural killer T cells, was also associated with the development of lung inflammatory diseases. FACS results indicated that Th17 cell was the main source of IL-17 in the infected pulmonary lymphocytes after phorbol-12-myristate-13-acetate (PMA) and Ionomycin stimulation. Moreover, FACS results revealed that the percentage of Th17 cells continued to increase as over the course of S. japonicum infection. Additionally, cytokines co-expression results demonstrated that Th17 cells could express more IL-4 and IL-5 than IFN-gamma. Reducing IL-17 activity by using anti-IL-17 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse lungs. Collectively, these results suggest Th17 cells is the major IL-17-producing cells population and IL-17 contributes to pulmonary granulomatous inflammatory during the S. japonicum infection. PMID- 24212064 TI - Increased mitochondrial fusion and autophagy help isolated hepatocytes repolarize in collagen sandwich cultures. AB - Freshly isolated, depolarized rat hepatocytes can repolarize into bile canalicular networks when plated in collagen sandwich cultures. We studied the events underlying this repolarization process, focusing on how hepatocytes restore ATP synthesis and resupply biosynthetic precursors after the stress of being isolated from liver. We found that soon after being plated in collagen sandwich cultures, hepatocytes converted their mitochondria into highly fused networks. This occurred through a combination of upregulation of mitochondrial fusion proteins and downregulation of a mitochondrial fission protein. Mitochondria also became more active for oxidative phosphorylation, leading to overall increased ATP levels within cells. We further observed that autophagy was upregulated in the repolarizing hepatocytes. Boosted autophagy levels likely served to recycle cellular precursors, supplying building blocks for repolarization. Repolarizing hepatocytes also extensively degraded lipid droplets, whose fatty acids provide precursors for ?-oxidation to fuel oxidative phosphorylation in mitochondria. Thus, through coordination of mitochondrial fusion, autophagy, and lipid droplet consumption, depolarized hepatocytes are able to boost ATP synthesis and biosynthetic precursors to efficiently repolarize in collagen sandwich cultures. PMID- 24212063 TI - Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia. AB - Lenalidomide is an IMID immunomodulatory agent clinically active in patients with chronic lymphocytic leukemia (CLL). We evaluated the activity of lenalidomide inside an in vitro coculture system of endothelial and CLL cells. Lenalidomide was able to inhibit CLL survival advantage mediated by endothelial contact. Moreover, the marked increase of in vitro angiogenesis determined by CLL-derived conditioned media was reduced by lenalidomide. We also analyzed peripheral blood collected from 27 patients with relapsed or refractory CLL being treated with lenalidomide within a phase II trial. Plasma levels of VEGF and THBS-1 decreased, whereas Ang2 and Ang increased during treatment. Patients who respond to lenalidomide showed a more pronounced decrease of VEGF and bFGF than did patients with stable or progressive disease (p = 0.007 and p = 0.005). Furthermore, lenalidomide reduced circulating endothelial cells and endothelial progenitors by increasing the percentage of apoptotic cells. Conversely, for six matched bone marrow biopsies available before and after treatment, we did not detect any modification in vessel density, suggesting a possible mechanism of vessel normalization rather than regression. In conclusion, our study provides further evidence that the anti-CLL effect of lenalidomide is mediated through the alteration of microenvironmental elements, implying the modulation of several angiogenesis-related factors and disruption of CLL crosstalk with endothelial cells. PMID- 24212065 TI - Determining the bioavailability and toxicity of lead contamination to earthworms requires using a combination of physicochemical and biological methods. AB - This study aimed at assessing the bioavailability and toxicity of lead to Eisenia andrei in shooting range soils representing different land uses (forest, grassland, bullet plot). Soils contained 47-2398 mg Pb/kg dry weight (dw), but also had different pH-CaCl2 (3.2-6.8) and organic matter contents (3.8-13%). Therefore artificial soils with different pH and organic matter contents and two natural soils were included as control soils. Earthworms were exposed for 28 days and toxicity and uptake of Pb were related to total, water and 0.01 M CaCl2 extractable and porewater Pb concentrations as well as to soil characteristics. Pb uptake in the earthworms linearly increased with increasing soil concentrations. At >2000 mg Pb/kg dw and pH 3.3-3.5, high earthworm mortality with significant weight loss and complete inhibition of reproduction were recorded. At <1000 mg/kg dw, earthworm reproduction was more related to differences in pH and other soil characteristics than to Pb. PMID- 24212066 TI - PCBs levels and indicator congeners in children's and adolescents' hair. AB - Thirty polychlorinated biphenyl (PCB) congeners were determined in the hair samples collected from children (4-12) and adolescents (13-18) of Changchun city, Northeastern China. The mean concentrations of total PCBs and dioxin-like PCBs (dl-PCBs) in the adolescents' hair samples were 161.0 ng g(-1) and 61.7 ng g(-1), which were relatively higher than 43.7 ng g(-1) and 14.6 ng g(-1) in the children's ones. Considering gender difference, the mean concentrations in the girls' hair samples were approximately two times higher than those in the boys' ones for most PCB congeners. The pentachlorinated biphenyl was the dominant homologue. It was found that the levels of total PCBs and dl-PCBs were highly correlated with PCB 118 level in the children's hair samples, and with PCB 114 level in the adolescents' ones. The result demonstrated that the two PCB congeners could be applied as the indicators to evaluate the concentrations of total PCBs and dl-PCBs in children's and adolescents' hair, respectively. PMID- 24212067 TI - Enhanced desorption of persistent organic pollutants from microplastics under simulated physiological conditions. AB - Microplastics have the potential to uptake and release persistent organic pollutants (POPs); however, subsequent transfer to marine organisms is poorly understood. Some models estimating transfer of sorbed contaminants to organisms neglect the role of gut surfactants under differing physiological conditions in the gut (varying pH and temperature), examined here. We investigated the potential for polyvinylchloride (PVC) and polyethylene (PE) to sorb and desorb (14)C-DDT, (14)C-phenanthrene (Phe), (14)C-perfluorooctanoic acid (PFOA) and (14)C-di-2-ethylhexyl phthalate (DEHP). Desorption rates of POPs were quantified in seawater and under simulated gut conditions. Influence of pH and temperature was examined in order to represent cold and warm blooded organisms. Desorption rates were faster with gut surfactant, with a further substantial increase under conditions simulating warm blooded organisms. Desorption under gut conditions could be up to 30 times greater than in seawater alone. Of the POP/plastic combinations examined Phe with PE gave the highest potential for transport to organisms. PMID- 24212068 TI - The contribution of a niche-based approach to ecological risk assessment: using macroinvertebrate species under multiple stressors. AB - We propose that a niche-based experimental approach at population level could be used to solve some uncertainties in traditional approaches in ecotoxicology. We tested this approach in the context of multiple stressors (i.e. chemical and physical) in a selection of six run-of-river reservoirs with different levels of sediment contamination and associated upstream and downstream river sites. A niche-based approach was tested using three functional traits (habitat, food preferences and body size) and discrepancy between the realized and theoretical niches. We first identified three groups of taxa and then recorded differences along the disturbance gradients, such as an increase in competition, a narrowing of spatial and trophic niche breadth (e.g. of Leuctra major and Gammarus pulex), a widening of spatial niche breadth (e.g. of Ephemerella ignita), a greater proportion of small individuals (e.g. of G. pulex) and a decreasing or an increasing (e.g. L. major) discrepancy between realized and theoretical niches. PMID- 24212069 TI - Increased expression of cutaneous alpha1-adrenoceptors after chronic constriction injury in rats. AB - alpha1-Adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether alpha1-adrenoceptor expression was upregulated on surviving peptidergic, nonpeptidergic, and myelinated nerve fiber populations in the skin after chronic constriction injury of the sciatic nerve in rats. Seven days after surgery, alpha1-adrenoceptor expression was upregulated in the epidermis and on dermal nerve fibers in plantar skin ipsilateral to the injury but not around blood vessels. This alpha1-adrenoceptor upregulation in the plantar skin was observed on all nerve fiber populations examined. However, alpha1-adrenoceptor expression was unaltered in the dorsal hind paw skin after the injury. The increased expression of alpha1-adrenoceptors on cutaneous nociceptors in plantar skin after chronic constriction injury suggests that this may be a site of sensory-sympathetic coupling that increases sensitivity to adrenergic agonists after nerve injury. In addition, activation of upregulated alpha1-adrenoceptors in the epidermis might cause release of factors that stimulate nociceptive signaling. PERSPECTIVE: Our findings indicate that peripheral nerve injury provokes upregulation of alpha1-adrenoceptors on surviving nociceptive afferents and epidermal cells in the skin. This might contribute to sympathetically maintained pain in conditions such as complex regional pain syndrome, painful diabetic neuropathy, and postherpetic neuralgia. PMID- 24212070 TI - Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain. AB - Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities and frequently by motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls. Analyses were carried out using a whole brain voxel-based morphometry approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems. PERSPECTIVE: This paper presents structural changes in the brains of patients with CRPS, helping us differentiate CRPS from other chronic pain syndromes and furthering our understanding of this challenging disease. PMID- 24212071 TI - The effect of Salvia divinorum and Mitragyna speciosa extracts, fraction and major constituents on place aversion and place preference in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Consumer use of botanicals has increased despite, in many instances, the paucity of research demonstrating efficacy or identifying liabilities. This research employed the place preference/aversion paradigm to characterize the psychoactive properties of Salvia divinorum extract (10, 30, 100mg/kg), salvinorin A (0.1, 0.3, 1.0mg/kg), Mitragyna speciosa MeOH extract (50, 100, 300 mg/kg), Mitragyna speciosa alkaloid-enriched fraction (12.5, 25, 75 mg/kg) and mitragynine (5, 10, 30 mg/kg) in rats. MATERIAL AND METHODS: Following apparatus habituation and baseline preference scores, male Sprague-Dawley rats were given eight counter-balanced drug versus vehicle conditioning trials followed by a preference test conducted under drug-free states. S(+)-amphetamine (1mg/kg) served as the positive control (in Exp. 2) and haloperidol (0.8, 1.0mg/kg) served as the negative control in both studies. RESULTS: Rats displayed place aversion to both Salvia divinorum and salvinorin A that exceeded that of haloperidol. Rats showed place preference to mitragynine that was similar to that of S(+)-amphetamine. This CPP effect was much less pronounced with the Mitragyna speciosa extract and its fraction. CONCLUSIONS: These findings suggest that both botanicals possess liabilities, albeit somewhat different, that warrant caution in their use. PMID- 24212072 TI - Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In hyperpigmentation disorders marked by melanin overproduction in the skin, including melisma and freckles, melanogenesis is caused by tyrosinase overexpression. Natural medicinal resources, like Phyla nodiflora, a traditional Chinese herbal medicine, have been used for a long time to management of dermatological conditions, such as skin inflammation and melanogenesis. Eupafolin, a functional flavonoid isolated from Phyla nodiflora, is an herbal tea constituent and possesses anti-inflammatory and anticancer activities. However, molecular mechanisms of eupafolin-mediated antimelanogenesis remain unknown. We thus focused on its antimelanogenesis effects in B16F10 mouse melanoma cells. MATERIAL AND METHODS: B16F10 cells were treated with eupafolin (0.01, 0.1, 1, and 10MUM) in a dose-escalation-dependent manner for the determination of melanin, tyrosinase activity and melanogenesis protein levels by ELISA or western blot analysis. RESULTS: Eupafolin treatment significantly reduced cellular melanin content and tyrosinase activity in a dose-dependent manner (P<0.05), and no cytotoxic effects were observed. Eupafolin was associated with reduction in the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase synthesis and tyrosinase-related protein expression, leading to inhibit melanin production. In addition, eupafolin significantly induced the phosphorylation of ERK1/2 and p38 MAPK, whereas the decreased effect was observed in the phosphorylation of Akt. Moreover, inhibitors of these signals recovered or attenuated the inhibitory effects of eupafolin on melanogenesis. CONCLUSIONS: Our results seem that inhibition of Akt and activation of phospho-ERK or p38 MAPK may lead to the suppression of melanogenesis in eupafolin-treated B16F10 mouse melanoma cells. PMID- 24212073 TI - Anti-fibrosis and anti-cirrhosis effects of Rhizoma paridis saponins on diethylnitrosamine induced rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla var. yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma paridis saponins (RPS), as the main active components of Paris polyphylla, have been used to treat liver injury. Anti-cirrhosis effect of Rhizoma paridis saponins (RPS) has not been known. MATERIALS AND METHODS: We analyzed diethylnitrosamine (DEN)-induced metabonomic changes in multiple biological matrices (plasma and urine) of rats by using (1)H-NMR spectroscopy together with clinical biochemistry assessments, oxidative stress test and DNA fragmentation assay. RESULTS: Mechanisms of RPS that participated in the inhibition of the fibrotic process included anti-oxidant, anti-apoptosis, and metabolic disturbance such as decreasing lipid oxidation, regulation of TCA cycle, carbohydrate, and amino acid metabolisms in DEN-induced liver tissues. CONCLUSIONS: Integrated NMR analysis of serum and urine samples, together with traditional clinical biochemical assays provided a holistic method for elucidating mechanisms of potential anti-fibrotic agent, RPS. PMID- 24212074 TI - Treatment with an extract of Terminalia superba Engler & Diels decreases blood pressure and improves endothelial function in spontaneously hypertensive rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Terminalia superba (TS) is widely used as a decoction by Cameroonian folk medicine for the treatment of hypertension. The aim of the present study was to evaluate the effect of a chronic treatment with a TS extract on spontaneously hypertensive rats (SHR) with respect to efficacy, biochemical mechanisms and safety. MATERIALS AND METHODS: Eleven-week-old SHR and normotensive Wistar Kyoto rats (WKY) were daily treated by gavage with a methylene chloride extract of stem bark of Terminalia superba (TMSE, 150mg/kg) or with the vehicle for 5 weeks. Systolic blood pressure (SBP) was measured weekly using the tail-cuff method. At the end of the treatment period, vascular function was assessed on isolated thoracic rings, urinary 8-iso PGF2alpha levels were measured and cytochrome P-450 3A (CYP 3A) activity was evaluated in liver microsomes. RESULTS: TMSE reduced SBP (P<0.001) in SHR but not in WKY rats. In SHR, the vasorelaxant response to acetylcholine was significantly improved by TMSE as a result of increased nitric oxide synthase (NO) activity and decreased superoxide anion production. In addition, TMSE reduced the vasoconstrictive effect of phenylephrine and improved the sensitivity of smooth muscle cells to NO. TMSE dramatically decreased 8-iso-PGF2alpha levels in SHR. By contrast, TMSE did not affect all these parameters in WKY rats. Neither diuresis nor the hepatic CYP 3A activity was modified in both animal groups. CONCLUSIONS: This study demonstrated that Terminalia superba has a potent antihypertensive activity in SHR which is partly due to endothelium-dependent and endothelium independent effects as well as decreased oxidative stress. The data also provide evidence for the lack of herb-drug interaction through hepatic CYP 3A. PMID- 24212075 TI - Towards a better understanding of medicinal uses of Carthamus tinctorius L. in traditional Chinese medicine: a phytochemical and pharmacological review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Carthamus tinctorius L. (Compositae), a widely used traditional Chinese medicine, was known as Hong hua (Chinese: ), safflower. Safflower with a wide spectrum of pharmacological effects has been used to treat dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma and pain of joints, etc. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology and toxicology of safflower. Finally, the possible tendency and perspective for future investigation of this plant are discussed, too. MATERIALS AND METHODS: The information on safflower was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, CNKI and others. RESULTS: Over 104 compounds from this plant have been isolated and identified, and quinochalcones and flavonoids are considered as the characteristic and active constituents of safflower. Safflower with its active compounds possesses wide-reaching biological activities, including dilating coronary artery, improving myocardial ischemia, modulating immune system, anticoagulation and antithrombosis, antioxidation, antiaging, antihypoxia, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. CONCLUSIONS: As an important traditional Chinese medicine, it is important to investigate the pharmacological effects and molecular mechanisms of this plant based on modern realization of diseases' pathophysiology. More bioactive components should be identified using bioactivity guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from safflower need to be evaluated integrating pharmacological, pharmacokinetic, bioavailability-centered and physiological approaches. Further studies on safflower can lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to. PMID- 24212076 TI - Protective effects of Huang-Lian-Jie-Du-Tang and its component group on collagen induced arthritis in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang is a famous Traditional Chinese medicine consisting of Rhizoma coptidis (Coptis chinensis Franch, Ranunculaceae), Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae), Cortex phellodendri (Phellodendron amurense Rupr. Rutaceae) and Fructus gardeniae (Gardenia jasminoide Ellis, Rubiaceae) in a weight ratio of 3:2:2:3.This formula was described by Wang Tao (in the Chinese Tang Dynasty) in his treatise "Wai Tai Mi Yao". It has been used to treat inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases in the clinical practice of Traditional Chinese medicine, especially in treating inflammation for nearly two thousand years. However, the essential compounds in it have not been identified, and the mechanisms remain to be addressed. To investigate the protective effects of HLJDT and its component group (HLJDT-CG) on collagen-induced arthritis in rats. MATERIALS AND METHODS: CIA was established in male Wistar rats with subcutaneous injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of HLJDT aqueous extracts (270 mg/kg) or HLJDT-CG (40 mg/kg) once per day from day 6 to day 28. Rats in normal and vehicle control groups were given an equal volume of vehicle (0.9% saline) and 0.025 mg/kg Dexamethasone was given to the Standard group at the same time. The protective effect of them were assessed by measuring arthritis index, swelling, the cytokines such as TNF-alpha, IFN-gamma and IL-17 in serum, type II collagen antibodies, splenocyte proliferation and so on. RESULTS: The results demonstrated that treatment of CIA rat with either HLJDT aqueous extracts or HLJDT-CG not only ameliorated the symptoms of arthritis, prevented joint damage but also reduced the serum levels of TNF-alpha, IFN-gamma and IL-17 in CIA rats. Anti-CII antibodies showed the similar trend except that of IgG1. Furthermore, HLJDT aqueous extracts and HLJDT-CG administration also suppressed CII-induced proliferative response of splenocytes. More importantly, HLJDT-CG exhibited similar pharmacological activities as HLJDT aqueous extracts in all aforementioned experiments. CONCLUSIONS: HLJDT aqueous extracts and HLJDT-CG could effectively ameliorate CII-induced arthritis and significantly suppress the immune response against CII with similar pharmacological efficacy. These findings suggest that HLJDT has therapeutic potential in RA treatment and HLJDT-CG can represent the effective-composite of HLJDT. PMID- 24212077 TI - Anti-inflammatory and antitumoural effects of Uncaria guianensis bark. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria guianensis (Aublet) Gmell (Rubiaceae) is a medicinal plant from the jungles of South and Central America, used to treat cancer, arthritis, diabetes, and inflammation. Evaluate the anti-inflammatory and anti-tumor effects of Uncaria guianensis preparations. MATERIALS AND METHODS: Bio guided fractionation of a hydroethanolic extract of Uncaria guianensis was performed, evaluating the fractions and subfractions for their effect on inflammatory mediators, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) by ELISA and nitric oxide (NO) by the Griess reaction in cultured supernatant from RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). The expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and inhibitor of kappaB (IkappaB) were investigated in RAW 264.7 macrophages by flow cytometry. The activity of NF-kappaB in HeLa cells transfected with a luciferase reporter system was determined. The effect of Uncaria guianensis on the inflammatory response in vivo was assessed in BALB/c mice stimulated with LPS, on rat paw oedema induced by carrageenan, and on tumour growth and lung metastasis in BALB/c mice inoculated with 4T1 mammary tumour cells. Immune cell infiltrates and inflammatory mediators were evaluated in the tumour by immunohistochemistry. RESULTS: Sub-fraction Ug AIV inhibited, to varying degrees, NO, TNF-alpha, IL-6 and PGE2 production by macrophages in vitro (30 MUg/ml) and in the serum of LPS-challenged mice (5 mg/kg). Macrophage expression of Cox-2 was inhibited (35%), IkappaB degradation was completely inhibited and NF-kappaB activation was inhibited (70%) by Ug AIV at 30 MUg/ml. Ug AIV decreased paw oedema by 86% (5 mg/kg) and serum NO and TNF-alpha by 45% and 65% respectively. Ug AIV reduced 4T1 mammary tumour growth by 91% on day 33 post inoculation as well as the levels of serum NO, IL-6 and TNF-alpha in the same animals. Ug AIV decreased the number of tumour-infiltrating T lymphocytes, macrophages and neutrophils as well as the number of cells positive for COX-2, iNOS, IL-6, TNF-alpha and p65. CONCLUSIONS: As Ug AIV was not cytotoxic for tumour cells or macrophages, its anti-tumour effect may be due to a reduction in pro-tumoural inflammatory processes in the tumour microenvironment, possibly mediated through NF-kappaB. PMID- 24212078 TI - Comparison of chemical compositions and osteoprotective effects of different sections of velvet antler. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Velvet antlers (VA) have been claimed for centuries to have numerous medical benefits including strengthen bones. To investigate and compare the anti-osteoporotic activities from different sections of VA. MATERIALS AND METHODS: Fresh VA prepared from farmed sika deers (Cervus nippon) was divided into upper (VAU), middle (VAM), and basal (VAB) sections. The chemical constituents and anti-osteoporotic effect of different sections from VA were evaluated using ovariectomized rats. RESULTS: Levels of water-soluble extracts, diluted alcoholic extract, amino acids, testosterone, insulin-like growth factor (IGF)-1 and testosterone plus estradiol significantly differed among the different sections. Levels of these constituents were significantly higher in the upper section than in the basal section. Moreover, levels of testosterone and IGF-1 of the VAM were also significantly higher than those of the VAB. Calcium level increased downward from the tip with statistical significance. The strength of vertebrae increased in all VA-treated groups compared to the control, but only treatment with VAU and VAM increased the strength of the femur and the microarchitecure of the trabecular bone. Alkaline phosphatase levels of VAU- and VAM-treated groups significantly decreased, but osteocalcin did not significantly change. Moreover, VAU and VAM dose-dependently increased proliferation and mineralization of MC3T3-E1 cells. CONCLUSION: Our study provides strong evidence for the regional differences in the effectiveness of velvet antler in treating osteoporosis. However, further studies are needed to elucidate the bioactive chemical constituents associated with the anti osteoporotic effects of velvet antler. PMID- 24212079 TI - Total alkaloids of Tripterygium hypoglaucum (levl.) Hutch inhibits tumor growth both in vitro and in vivo. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (levl.) Hutch (Celastraceae) (THH) root is a traditional Chinese medicinal herb commonly used for treating autoimmune diseases and cancer. Alkaloid is one of the most bioactive components of THH extract. To evaluate the in vitro and in vivo antitumor properties of the total alkaloids of THH (THHta). MATERIALS AND METHODS: THHta was extracted in pilot-scale. HCT116 cells were chose to establish human colon cancer xenograft model. The in vitro anti-tumor activity of THHta was tested by Cell malignant transformation test, Soft agar colony formation assay and MTT assay. The in vivo anti-tumor effect of THHta was confirmed by xenograft mouse model. THHta-induced apoptosis was examined by flow cytometry. The levels of apoptosis-related proteins were investigated by Western blot. RESULTS: TPA induced cell transformation was significantly inhibited by THHta in JB6 Cl41 cells. THHta inhibits the growth of colon cancer cells in vitro in a significant dose-dependent manner. Compared to the control set, i.p. administration of THHta to xenograft mice significantly reduced both tumor weight and volume. Apoptosis induction of THHta was mediated by activation of caspase-3, PARP and inhibiting of Bcl-2, Bcl-xL and XIAP. CONCLUSION: THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent. PMID- 24212080 TI - An alternative to the breeder's and Lande's equations. AB - The breeder's equation is a cornerstone of quantitative genetics, widely used in evolutionary modeling. Noting the mean phenotype in parental, selected parents, and the progeny by E(Z0), E(ZW), and E(Z1), this equation relates response to selection R = E(Z1) - E(Z0) to the selection differential S = E(ZW) - E(Z0) through a simple proportionality relation R = h(2)S, where the heritability coefficient h(2) is a simple function of genotype and environment factors variance. The validity of this relation relies strongly on the normal (Gaussian) distribution of the parent genotype, which is an unobservable quantity and cannot be ascertained. In contrast, we show here that if the fitness (or selection) function is Gaussian with mean MU, an alternative, exact linear equation of the form R' = j(2)S' can be derived, regardless of the parental genotype distribution. Here R' = E(Z1) - MU and S' = E(ZW) - MU stand for the mean phenotypic lag with respect to the mean of the fitness function in the offspring and selected populations. The proportionality coefficient j(2) is a simple function of selection function and environment factors variance, but does not contain the genotype variance. To demonstrate this, we derive the exact functional relation between the mean phenotype in the selected and the offspring population and deduce all cases that lead to a linear relation between them. These results generalize naturally to the concept of G matrix and the multivariate Lande's equation Delta(z) = GP(-1)S. The linearity coefficient of the alternative equation are not changed by Gaussian selection. PMID- 24212081 TI - Genetic variation and covariation in male attractiveness and female mating preferences in Drosophila melanogaster. AB - How mating preferences evolve remains one of the major unsolved mysteries in evolutionary biology. One major impediment to the study of ornament-preference coevolution is that many aspects of the theoretical literature remain loosely connected to empirical data. Theoretical models typically streamline mating preferences by describing preference functions with a single parameter, a modeling convenience that may veil important aspects of preference evolution. Here, we use a high-throughput behavioral assay in Drosophila melanogaster to quantify attractiveness and multiple components of preferences in both males and females. Females varied genetically with respect to how they ranked males in terms of attractiveness as well as the extent to which they discriminated among different males. Conversely, males showed consistent preferences for females, suggesting that D. melanogaster males tend to rank different female phenotypes in the same order in terms of attractiveness. Moreover, we reveal a heretofore undocumented positive genetic correlation between male attractiveness and female choosiness, which is a measure of the variability in a female's response to different male phenotypes. This genetic correlation sets the stage for female choosiness to evolve via a correlated response to selection on male traits and potentially adds a new dimension to the Fisherian sexual selection process. PMID- 24212082 TI - The use of SNP markers for linkage mapping in diploid and tetraploid peanuts. AB - Single nucleotide polymorphic markers (SNPs) are attractive for use in genetic mapping and marker-assisted breeding because they can be scored in parallel assays at favorable costs. However, scoring SNP markers in polyploid plants like the peanut is problematic because of interfering signal generated from the DNA bases that are homeologous to those being assayed. The present study used a previously constructed 1536 GoldenGate SNP assay developed using SNPs identified between two A. duranensis accessions. In this study, the performance of this assay was tested on two RIL mapping populations, one diploid (A. duranensis * A. stenosperma) and one tetraploid [A. hypogaea cv. Runner IAC 886 * synthetic tetraploid (A. ipaensis * A. duranensis)(4*)]. The scoring was performed using the software GenomeStudio version 2011.1. For the diploid, polymorphic markers provided excellent genotyping scores with default software parameters. In the tetraploid, as expected, most of the polymorphic markers provided signal intensity plots that were distorted compared to diploid patterns and that were incorrectly scored using default parameters. However, these scorings were easily corrected using the GenomeStudio software. The degree of distortion was highly variable. Of the polymorphic markers, approximately 10% showed no distortion at all behaving as expected for single-dose markers, and another 30% showed low distortion and could be considered high-quality. The genotyped markers were incorporated into diploid and tetraploid genetic maps of Arachis and, in the latter case, were located almost entirely on A genome linkage groups. PMID- 24212083 TI - High-sensitivity cardiac troponin I for predicting death in a female emergency department population. PMID- 24212084 TI - Novel biomarkers for acute myocardial infarction: is microRNA the new kid on the block? PMID- 24212085 TI - Circulating U2 small nuclear RNA fragments as a novel diagnostic tool for patients with epithelial ovarian cancer. AB - BACKGROUND: Ovarian cancer is the leading cause of death among malignancies in women. Despite advances in treatment, >50% of patients relapse. For disease monitoring, the identification of a blood-based biomarker would be of prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or small nuclear RNA (snRNA), have been suggested as biomarkers for noninvasive cancer diagnosis. In the present study, we sought to identify differentially expressed miRNA/snRNA in sera of ovarian cancer patients and investigate their potential to aid in therapy monitoring. METHODS: miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n = 119) by reverse-transcription quantitative PCR. RESULTS: Abundance of U2-1 snRNA fragment (RNU2-1f) was significantly increased in sera of ovarian cancer patients (P < 0.0001) and paralleled International Federation of Gynecology and Obstetrics stage as well as residual tumor burden after surgery (P < 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated with radiographic response after chemotherapy and with platinum resistance (P = 0.0088 and P = 0.0015, respectively). Interestingly, according to the RNU2-1f abundance dynamics, persistent RNU2-1f positivity before surgery and after chemotherapy identified a subgroup of patients with high risk of recurrence and poor prognosis. CONCLUSIONS: This is the first report to suggest that a circulating snRNA can serve as an auxiliary diagnostic tool for monitoring tumor dynamics in ovarian cancer. Our results provide a rationale to further investigate whether this high risk patient group may benefit from additional therapies that are directly applied after chemotherapy. PMID- 24212086 TI - Peptidomics of urine and other biofluids for cancer diagnostics. AB - BACKGROUND: Cancer is a leading cause of death worldwide. The low diagnostic sensitivity and specificity of most current cancer biomarkers make early cancer diagnosis a challenging task. The comprehensive study of peptides and small proteins in a living system, known as "peptidomics," represents an alternative technological approach to the discovery of potential biomarkers for the assessment of a wide variety of pathologies. This review examines the current status of peptidomics for several body fluids, with a focus on urine, for cancer diagnostics applications. CONTENT: Several studies have used high-throughput technologies to characterize the peptide content of different body fluids. Because of its noninvasive collection and high stability, urine is a valuable source of candidate cancer biomarkers. A wide variety of preanalytical issues concerning patient selection and sample handling need to be considered, because not doing so can affect the quality of the results by introducing bias and artifacts. Optimization of both the analytical strategies and the processing of bioinformatics data is also essential to minimize the false-discovery rate. SUMMARY: Peptidomics-based studies of urine and other body fluids have yielded a number of biomolecules and peptide panels with potential for diagnosing different types of cancer, especially of the ovary, prostate, and bladder. Large-scale studies are needed to validate these molecules as cancer biomarkers. PMID- 24212087 TI - Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing. AB - BACKGROUND: Accurate evaluation of unclassified sequence variants in cancer predisposition genes is essential for clinical management and depends on a multifactorial analysis of clinical, genetic, pathologic, and bioinformatic variables and assays of transcript length and abundance. The integrity of assay data in turn relies on appropriate assay design, interpretation, and reporting. METHODS: We conducted a multicenter investigation to compare mRNA splicing assay protocols used by members of the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) consortium. We compared similarities and differences in results derived from analysis of a panel of breast cancer 1, early onset (BRCA1) and breast cancer 2, early onset (BRCA2) gene variants known to alter splicing (BRCA1: c.135-1G>T, c.591C>T, c.594-2A>C, c.671-2A>G, and c.5467+5G>C and BRCA2: c.426-12_8delGTTTT, c.7988A>T, c.8632+1G>A, and c.9501+3A>T). Differences in protocols were then assessed to determine which elements were critical in reliable assay design. RESULTS: PCR primer design strategies, PCR conditions, and product detection methods, combined with a prior knowledge of expected alternative transcripts, were the key factors for accurate splicing assay results. For example, because of the position of primers and PCR extension times, several isoforms associated with BRCA1, c.594-2A>C and c.671 2A>G, were not detected by many sites. Variation was most evident for the detection of low-abundance transcripts (e.g., BRCA2 c.8632+1G>A Delta19,20 and BRCA1 c.135-1G>T Delta5q and Delta3). Detection of low-abundance transcripts was sometimes addressed by using more analytically sensitive detection methods (e.g., BRCA2 c.426-12_8delGTTTT ins18bp). CONCLUSIONS: We provide recommendations for best practice and raise key issues to consider when designing mRNA assays for evaluation of unclassified sequence variants. PMID- 24212088 TI - Vitamin K status in chronic kidney disease. AB - The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population. PMID- 24212089 TI - The influence of vitamin A supplementation on iron status. AB - Vitamin A (VA) and iron deficiencies are important nutritional problems, affecting particularly preschool children, as well as pregnant and lactating women. A PubMed (National Library of Medicine, National Institutes of Health, Bethesda, MD, USA) literature review was carried out to search for clinical trials published from 1992 to 2013 that assessed the influence of vitamin A supplementation on iron status. Simultaneous use of iron and vitamin A supplements seemed to be more effective to prevent iron deficiency anemia than the use of these micronutrients alone. Some studies did not include a placebo group and only a few of them assessed vitamin A status of the individuals at baseline. Moreover, the studies did not consider any inflammatory marker and a reasonable number of iron parameters. Another important limitation was the lack of assessment of hemoglobin variants, especially in regions with a high prevalence of anemia. Assessment of hemoglobin variants, inflammatory markers and anemia of chronic inflammation would be important to the studies investigated. Studies involving different populations are necessary to elucidate the interaction between the two micronutrients, especially regarding iron absorption and modulation of erythropoiesis. PMID- 24212090 TI - Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch. AB - Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Factors that induce brown adipocyte commitment and energy expenditure would be a promising defence against adiposity. Here, we show that Lgr4 homozygous mutant (Lgr4(m/m)) mice show reduced adiposity and resist dietary and leptin mutant-induced obesity with improved glucose metabolism. Lgr4(m/m) mice show a striking increase in energy expenditure, and exhibit brown-like adipocytes in WAT depots with higher expression of BAT and beige cell markers. Furthermore, Lgr4 ablation potentiates brown adipocyte differentiation from the stromal vascular fraction of epididymal WAT, partially through retinoblastoma 1 gene (Rb1) reduction. A functional low-frequency human LGR4 variant (A750T) has been associated with body mass index in a Chinese obese versus-control study. Our results identify an important role for LGR4 in energy balance and body weight control through regulating the white-to-brown fat transition. PMID- 24212091 TI - The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. AB - Mitochondrial calcium has been postulated to regulate a wide range of processes from bioenergetics to cell death. Here, we characterize a mouse model that lacks expression of the recently discovered mitochondrial calcium uniporter (MCU). Mitochondria derived from MCU(-/-) mice have no apparent capacity to rapidly uptake calcium. Whereas basal metabolism seems unaffected, the skeletal muscle of MCU(-/-) mice exhibited alterations in the phosphorylation and activity of pyruvate dehydrogenase. In addition, MCU(-/-) mice exhibited marked impairment in their ability to perform strenuous work. We further show that mitochondria from MCU(-/-) mice lacked evidence for calcium-induced permeability transition pore (PTP) opening. The lack of PTP opening does not seem to protect MCU(-/-) cells and tissues from cell death, although MCU(-/-) hearts fail to respond to the PTP inhibitor cyclosporin A. Taken together, these results clarify how acute alterations in mitochondrial matrix calcium can regulate mammalian physiology. PMID- 24212092 TI - Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. AB - Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly. PMID- 24212093 TI - SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. AB - Actin's polymerization properties are markedly altered by oxidation of its conserved Met 44 residue. Mediating this effect is a specific oxidation-reduction (redox) enzyme, Mical, that works with Semaphorin repulsive guidance cues and selectively oxidizes Met 44. We now find that this actin-regulatory process is reversible. Employing a genetic approach, we identified a specific methionine sulfoxide reductase (MsrB) enzyme SelR that opposes Mical redox activity and Semaphorin-Plexin repulsion to direct multiple actin-dependent cellular behaviours in vivo. SelR specifically catalyses the reduction of the R isomer of methionine sulfoxide (methionine-R-sulfoxide) to methionine, and we found that SelR directly reduced Mical-oxidized actin, restoring its normal polymerization properties. These results indicate that Mical oxidizes actin stereospecifically to generate actin Met-44-R-sulfoxide (actin(Met(R)O-44)), and also implicate the interconversion of specific Met/Met(R)O residues as a precise means to modulate protein function. Our results therefore uncover a specific reversible redox actin regulatory system that controls cell and developmental biology. PMID- 24212094 TI - Dynamic modeling and validation of a lignocellulosic enzymatic hydrolysis process -a demonstration scale study. AB - The enzymatic hydrolysis process is one of the key steps in second generation biofuel production. After being thermally pretreated, the lignocellulosic material is liquefied by enzymes prior to fermentation. The scope of this paper is to evaluate a dynamic model of the hydrolysis process on a demonstration scale reactor. The following novel features are included: the application of the Convection-Diffusion-Reaction equation to a hydrolysis reactor to assess transport and mixing effects; the extension of a competitive kinetic model with enzymatic pH dependency and hemicellulose hydrolysis; a comprehensive pH model; and viscosity estimations during the course of reaction. The model is evaluated against real data extracted from a demonstration scale biorefinery throughout several days of operation. All measurements are within predictions uncertainty and, therefore, the model constitutes a valuable tool to support process optimization, performance monitoring, diagnosis and process control at full-scale studies. PMID- 24212095 TI - Stoichiometry-controlled FeP nanoparticles synthesized from a single source precursor. AB - Phase-pure FeP nanoparticles (NPs) have been synthesized through low temperature thermolysis of the single source precursor [(CO)4Fe(PH3)]. Examination of the mechanism demonstrates the central role of the labile CO ligands and the weak P-H bonds to yield stoichiometry controlled FeP materials. PMID- 24212096 TI - Characteristics of TCR/CD3 complex CD3{varepsilon} chains of regulatory CD4+ T (Treg) lymphocytes: role in Treg differentiation in vitro and impact on Treg in vivo. AB - Tregs are anergic CD4(+)CD25(+)Foxp3(+) T lymphocytes exerting active suppression to control immune and autoimmune responses. However, the factors in TCR recognition underlying Treg differentiation are unclear. Based on our previous data, we hypothesized that Treg TCR/CD3 antigen receptor complexes might differ from those of CD4(+)CD25(-) Tconv. Expression levels of TCR/CD3, CD3epsilon,zeta chains, or other molecules involved in antigen signaling and the characteristics of CD3epsilon chains were analyzed in thymus or spleen Treg cells from normal mice. Tregs had quantitative and qualitatively distinct TCR/CD3 complexes and CD3epsilon chains. They expressed significantly lower levels of the TCR/CD3 antigen receptor, CD3epsilon chains, TCR-zeta chain, or the CD4 coreceptor than Tconv. Levels of kinases, adaptor molecules involved in TCR signaling, and early downstream activation pathways were also lower in Tregs than in Tconv. Furthermore, TCR/CD3 complexes in Tregs were enriched in CD3epsilon chains conserving their N-terminal, negatively charged amino acid residues; this trait is linked to a higher activation threshold. Transfection of mutant CD3epsilon chains lacking these residues inhibited the differentiation of mature CD4(+)Foxp3(-) T lymphocytes into CD4(+)Foxp3(+) Tregs, and differences in CD3epsilon chain recognition by antibodies could be used to enrich for Tregs in vivo. Our results show quantitative and qualitative differences in the TCR/CD3 complex, supporting the hyporesponsive phenotype of Tregs concerning TCR/CD3 signals. These differences might reconcile avidity and flexible threshold models of Treg differentiation and be used to implement therapeutic approaches involving Treg manipulation. PMID- 24212097 TI - CD14(hi)HLA-DR(dim) macrophages, with a resemblance to classical blood monocytes, dominate inflamed mucosa in Crohn's disease. AB - Intestinal M play an important role in maintaining gut homeostasis. However, little is known about these cells, their precursors, and their role in intestinal inflammation. Here, we characterize the CD14(+) mononuclear cell populations in intestinal mucosa and blood in patients with CD. Among the LP CD14(+) M, we identified three distinct HLA-DR(+)-expressing subsets. Compared with uninflamed, inflamed mucosa contained a marked increase in the proportion of the CD14(hi)HLA DR(dim) cellular subset. This subset resembled the classical blood monocytes with low CD16, HLA-DR, and CX3CR1 expression. Classical monocytes migrated efficiently toward CCL2 and released the highest levels of MMP-1 and proinflammatory cytokines when stimulated with immune complexes or LPS. Our findings strongly suggest that it is the classical and not the intermediate or nonclassical monocytes that are the precursors to the dominating intestinal CD14(hi)HLA DR(dim) subset. This enhances our understanding of CD pathology and may provide new options in treatment. PMID- 24212099 TI - Technical Advance: a new cell preparation strategy that greatly improves the yield of vital and functional Tregs and NKT cells. AB - Release of NAD(+) during preparation of murine lymphocytes causes enzymatic ADP ribosylation of cell-surface proteins on T cells, catalyzed by toxin-related ecto ADP-ribosyltransferase, ARTC2. ADP-riboslyation activates the cytolytic P2X7 ion channel and affects, in particular, the vitality and function of Tregs and NKT cells. Here, we describe a simple method-injection of an ARTC2-blocking nanobody to greatly improve Treg and NKT cell vitality and to preserve their function during in vitro assays and in adoptive-transfer experiments. Moreover, we present a method for the sorting of functional, primary NKT cells, based on coexpression of ARTC2 and NK1.1. Our results pave the way for the efficient ex vivo proliferation of Tregs and NKT cells and for new experimental and therapeutic uses of these important regulatory cells. PMID- 24212100 TI - Dynamical and topological robustness of the mammalian cell cycle network: a reverse engineering approach. AB - A common gene regulatory network model is the threshold Boolean network, used for example to model the Arabidopsis thaliana floral morphogenesis network or the fission yeast cell cycle network. In this paper, we analyze a logical model of the mammalian cell cycle network and its threshold Boolean network equivalent. Firstly, the robustness of the network was explored with respect to update perturbations, in particular, what happened to the attractors for all the deterministic updating schemes. Results on the number of different limit cycles, limit cycle lengths, basin of attraction size, for all the deterministic updating schemes were obtained through mathematical and computational tools. Secondly, we analyzed the topology robustness of the network, by reconstructing synthetic networks that contained exactly the same attractors as the original model by means of a swarm intelligence approach. Our results indicate that networks may not be very robust given the great variety of limit cycles that a network can obtain depending on the updating scheme. In addition, we identified an omnipresent network with interactions that match with the original model as well as the discovery of new interactions. The techniques presented in this paper are general, and can be used to analyze other logical or threshold Boolean network models of gene regulatory networks. PMID- 24212098 TI - The two faces of heterologous immunity: protection or immunopathology. AB - Immunity to previously encountered viruses can alter responses to unrelated pathogens. This phenomenon, which is known as heterologous immunity, has been well established in animal model systems. Heterologous immunity appears to be relatively common and may be beneficial by boosting protective responses. However, heterologous reactivity can also result in severe immunopathology. The key features that define heterologous immune modulation include alterations in the CD4(+) and CD8(+) T cell compartments and changes in viral dynamics and disease progression. In this review, we discuss recent advances and the current understanding of antiviral immunity in heterologous infections. The difficulties of studying these complex heterologous infections in humans are discussed, with special reference to the variations in HLA haplotypes and uncertainties about individuals' infection history. Despite these limitations, epidemiological analyses in humans and the data from mouse models of coinfection can be applied toward advancing the design of therapeutics and vaccination strategies. PMID- 24212101 TI - Connected health: cancer symptom and quality-of-life assessment using a tablet computer: a pilot study. AB - Incorporation of tablet computers (TCs) into patient assessment may facilitate safe and secure data collection. We evaluated the usefulness and acceptability of a TC as an electronic self-report symptom assessment instrument. Research Electronic Data Capture Web-based application supported data capture. Information was collected and disseminated in real time and a structured format. Completed questionnaires were printed and given to the physician before the patient visit. Most participants completed the survey without assistance. Completion rate was 100%. The median global quality of life was high for all. More than half reported pain. Based on Edmonton Symptom Assessment System, the top 3 most common symptoms were tiredness, anxiety, and decreased well-being. Patient and physician acceptability for these quick and useful TC-based surveys was excellent. PMID- 24212102 TI - Racial disparities in receipt of hospice services among nursing home residents. AB - This study examined the relationship between race and advance care planning, hospitalization, and death among nursing home residents receiving hospice care. Secondary data analysis using the 2007 Minimum Data Set (MDS) was used to identify documentation of these activities for White, Black, Hispanic, and Asian residents with linear regression models fitted to each dependent variable. Across different types of advance directives, compared to White nursing home residents, Black, Hispanic, and Asian residents who received hospice services were significantly less likely overall to have documented advance directives. All racial groups were also more likely to experience hospitalization while on hospice, regardless of whether they had a documented "do not hospitalize" order. As nursing homes become more diverse, recognizing differences in hospice use and end-of-life planning will continue to increase in importance. PMID- 24212103 TI - Absence of congruency sequence effects reveals neurocognitive inflexibility in Parkinson's disease. AB - The effects of Parkinson's disease (PD) on action selection in conflictual situations were examined in an experiment using the flanker task in combination with event-related brain potentials (ERPs). More specifically, we investigated the effects of PD on behavioral and neuronal indicators of both instantaneous (within-trial flanker congruency effects) and sequence-dependent (between-trial congruency sequence effects) distractor interference. Consistent with the existing literature, congruency-sensitive ERP components (i.e., fronto-central N2 and positive 'dips' of the lateralized readiness potential, LRP) were observed over medial-frontal and lateral-central regions, respectively. For situations requiring instantaneous action control, patients with PD and healthy controls showed similar congruency effects on reaction time, as well as on N2 and LRP 'dip' amplitudes. As expected, controls showed reliable congruency sequence effects on reaction time, as well as on N2 and LRP 'dip' amplitudes. However, patients with PD were completely unaffected by the congruence sequence across consecutive trials, as revealed by reaction time, as well as by N2 and LRP 'dip' amplitudes. The data imply that the effects of PD on action selection are largely restricted to a lack of adaptive modulation in time which we refer to as neurocognitive inflexibility, in the context of relatively spared abilities to instantaneously exert control over action selection. The findings are discussed in terms of basal ganglia dysfunction induced by PD which results primarily either in executive function deficits or in aberrant habit formation. PMID- 24212104 TI - Morphing surfaces enable acoustophoretic contactless transport of ultrahigh density matter in air. AB - The controlled contactless transport of heavy drops and particles in air is of fundamental interest and has significant application potential. Acoustic forces do not rely on special material properties, but their utility in transporting heavy matter in air has been restricted by low power and poor controllability. Here we present a new concept of acoustophoresis, based on the morphing of a deformable reflector, which exploits the low reaction forces and low relaxation time of a liquid with enhanced surface tension through the use of thin overlaid membrane. An acoustically induced, mobile deformation (dimple) on the reflector surface enhances the acoustic field emitted by a line of discretized emitters and enables the countinuos motion of heavy levitated samples. With such interplay of emitters and reflecting soft-structure, a 5 mm steel sphere (0.5 grams) was contactlessly transported in air solely by acoustophoresis. PMID- 24212105 TI - Global determinants of mortality in under 5s: 10 year worldwide longitudinal study. AB - OBJECTIVE: To assess at country level the association of mortality in under 5s with a large set of determinants. DESIGN: Longitudinal study. SETTING: 193 United Nations member countries, 2000-09. METHODS: Yearly data between 2000 and 2009 based on 12 world development indicators were used in a multivariable general additive mixed model allowing for non-linear relations and lag effects. MAIN OUTCOME MEASURE: National rate of deaths in under 5s per 1000 live births RESULTS: The model retained the variables: gross domestic product per capita; percentage of the population having access to improved water sources, having access to improved sanitation facilities, and living in urban areas; adolescent fertility rate; public health expenditure per capita; prevalence of HIV; perceived level of corruption and of violence; and mean number of years in school for women of reproductive age. Most of these variables exhibited non-linear behaviours and lag effects. CONCLUSIONS: By providing a unified framework for mortality in under 5s, encompassing both high and low income countries this study showed non-linear behaviours and lag effects of known or suspected determinants of mortality in this age group. Although some of the determinants presented a linear action on log mortality indicating that whatever the context, acting on them would be a pertinent strategy to effectively reduce mortality, others had a threshold based relation potentially mediated by lag effects. These findings could help designing efficient strategies to achieve maximum progress towards millennium development goal 4, which aims to reduce mortality in under 5s by two thirds between 1990 and 2015. PMID- 24212106 TI - Don't restrict funding from drug companies for doctors' education. PMID- 24212108 TI - Determinants of childhood mortality. PMID- 24212107 TI - Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta analysis. AB - OBJECTIVE: To compare the efficacy and safety of biodegradable polymer drug eluting stents with those of bare metal stents and durable polymer drug eluting stents. DESIGN: Mixed treatment comparison meta-analysis of 258,544 patient years of follow-up from randomized trials. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and Central were searched for randomized trials comparing any of the Food and Drug Administration approved durable polymer drug eluting stents (sirolimus eluting, paclitaxel eluting, cobalt chromium everolimus eluting, platinum chromium everolimus eluting, zotarolimus eluting-Endeavor, and zotarolimus eluting-Resolute) or biodegradable polymer drug eluting stents, with each other or against bare metal stents. OUTCOMES: Long term efficacy (target vessel revascularization, target lesion revascularization) and safety (death, myocardial infarction, stent thrombosis). Landmark analysis at more than one year was evaluated to assess the potential late benefit of biodegradable polymer drug eluting stents. RESULTS: From 126 randomized trials and 258,544 patient years of follow-up, for long term efficacy (target vessel revascularization), biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.66, 95% credibility interval 0.57 to 0.78) and zotarolimus eluting stent-Endeavor (0.69, 0.56 to 0.84) but not to newer generation durable polymer drug eluting stents (for example: 1.03, 0.89 to 1.21 versus cobalt chromium everolimus eluting stents). Similarly, biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.61, 0.37 to 0.89) but inferior to cobalt chromium everolimus eluting stents (2.04, 1.27 to 3.35) for long term safety (definite stent thrombosis). In the landmark analysis after one year, biodegradable polymer drug eluting stents were superior to sirolimus eluting stents for definite stent thrombosis (rate ratio 0.29, 0.10 to 0.82) but were associated with increased mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents. CONCLUSIONS: Biodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven. PMID- 24212109 TI - Power to the people: what will bring about the patient centred revolution? PMID- 24212110 TI - US lawyers investigate trial that secured license for AstraZeneca's antiplatelet drug. PMID- 24212111 TI - Litigation in maternity care is rising, says National Audit Office. PMID- 24212112 TI - UK doctor arrested in Syria is located in Damascus prison. PMID- 24212113 TI - Local topographic influences on vision restoration hot spots after brain damage. AB - PURPOSE: Vision restoration training (VRT) in hemianopia patients leads to visual field enlargements, but the mechanisms of this vision restoration are not known. To investigate the role of residual vision in recovery, we studied topographic features of visual field charts and determined residual functions in local regions and their immediate surround. METHODS: We analyzed High Resolution Perimetry visual field charts of hemianopic stroke patients (n = 23) before and after 6 months of VRT and identified all local visual field regions with ("hot spots", n = 688) or without restoration ("cold spots", n = 3426). Topographic features of these spots at baseline where then related to (i) their respective local residual function, (ii) residual activity in their spatial neighbourhood, and (iii) their distance to the scotoma border estimated in cortical coordinates following magnification factor transformation. RESULTS: Visual field areas had a greater probability of becoming vision restoration hot spots if they had more residual activity in both local areas and in a spatially limited surround of 5 degrees of visual angle. Hot spots were typically also located closer than 4 mm from the scotoma border in cortical coordinates. Thus, restoration depended on residual activity in both the local region and its immediate surround. CONCLUSIONS: Our findings confirm the special role of residual structures in visual field restoration which is likely mediated by partially surviving neuronal elements. Because the immediate but not distant surround influenced outcome of individual spots, we propose that lateral interactions, known to play a role in perceptual learning and receptive field plasticity, also play a major role in vision restoration. PMID- 24212114 TI - In this issue of Channels: Special issue on STIM and Orai. PMID- 24212115 TI - Predicting the biological variability of environmental rhythms: weak or strong anticipation for sensorimotor synchronization? AB - The internal processes involved in synchronizing our movements with environmental stimuli have traditionally been addressed using regular metronomic sequences. Regarding real-life environments, however, biological rhythms are known to have intrinsic variability, ubiquitously characterized as fractal long-range correlations. In our research we thus investigate to what extent the synchronization processes drawn from regular metronome paradigms can be generalized to other (biologically) variable rhythms. Participants performed synchronized finger tapping under five conditions of long-range and/or short range correlated, randomly variable, and regular auditory sequences. Combining experimental data analysis and numerical simulation, we found that synchronizing with biologically variable rhythms involves the same internal processes as with other variable rhythms (whether totally random or comprising lawful regularities), but different from those involved with a regular metronome. This challenges both the generalizability of conclusions drawn from regular-metronome paradigms, and recent research assuming that biologically variable rhythms may trigger specific strong anticipatory processes to achieve synchronization. PMID- 24212116 TI - Modulating younger and older adults' performance in ignoring pictorial information during a word matching task. AB - Using both behavioural and event-related potential (ERP) data, the current study sought to examine the neurophysiological underpinnings for the effect of distracting pictorial information on semantic word matching performance in younger and older adults. This was tested in the context of semantic relations between task-relevant word pairs, a task-irrelevant picture and the resultant N400 differences in ERP. Younger and older adults were shown a context word superimposed on a to-be-ignored picture, followed by a test word. Their task was to determine whether the prime and test words were semantically related. The to be-ignored pictures were interfering (for 'No' trials), facilitating (for 'Yes' trials), or neutral (for both 'Yes' and 'No' trials) to the expected responses. The interfering and facilitatory effects of to-be-ignored pictures were assessed under more automatic and more controlled conditions by manipulating the context test interstimulus-interval (ISI) as 50ms and 1000ms, respectively. The analysis of the N400 at centro-parietal sites during test word display revealed similar N400 amplitudes for the 'No' response trials at the two ISIs, suggesting that younger and older adults showed an equivalent effect from interfering pictures. In contrast, younger adults showed greater reductions in the N400, as compared to older adults, for 'Yes' trials indicating differential effects in facilitation from to-be-ignored pictorial information, but only in the long ISI condition. The data are discussed in terms of age differences in resource demanding strategy use during a semantic word matching task, specifically during controlled retrieval. PMID- 24212117 TI - Purification, structure and anti-radiation activity of melanin from Lachnum YM404. AB - Extracellular melanins (LEM404) were extracted from Lachnum YM404 with a yield of 3.45 g/L. LEM404-a, LEM404-b, LEM404-c, LEM404-d and LEM404-e were fractionated from LEM404 by Sephadex G-15 column. LE404-a was detected as the homogeneous component with molecular weight of about 432.18 Da. Based on the elemental analysis, mass spectrometry, infrared spectroscopy, pyrolysis-GC-MS and NMR analysis, the molecular formula (C22H12N2O4S2) and structural formula of LEM404-a were concluded. LEM404-a could significantly increase the survival rates of Escherichia coli, Staphylococcus aureus and Saccharomyces cerevisiae under UV radiation. Anti-radiation experiments in mice showed that the skin manifestations in mice of low radiation dose experimental group (LEG) were similar to those in blank control group (BCG). Compared with the control groups (LCG and HCG), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in mice of experiment groups (LEG and HEG) were improved significantly while malondialdehyde (MDA) content were decreased significantly, indicating that LEM404-a had strong anti-ultraviolet radiation activity. PMID- 24212118 TI - Towards generating a patient's timeline: extracting temporal relationships from clinical notes. AB - Clinical records include both coded and free-text fields that interact to reflect complicated patient stories. The information often covers not only the present medical condition and events experienced by the patient, but also refers to relevant events in the past (such as signs, symptoms, tests or treatments). In order to automatically construct a timeline of these events, we first need to extract the temporal relations between pairs of events or time expressions presented in the clinical notes. We designed separate extraction components for different types of temporal relations, utilizing a novel hybrid system that combines machine learning with a graph-based inference mechanism to extract the temporal links. The temporal graph is a directed graph based on parse tree dependencies of the simplified sentences and frequent pattern clues. We generalized the sentences in order to discover patterns that, given the complexities of natural language, might not be directly discoverable in the original sentences. The proposed hybrid system performance reached an F-measure of 0.63, with precision at 0.76 and recall at 0.54 on the 2012 i2b2 Natural Language Processing corpus for the temporal relation (TLink) extraction task, achieving the highest precision and third highest f-measure among participating teams in the TLink track. PMID- 24212119 TI - Sensitivity characteristic analysis of adsorbent-mixed carbon nanotube sensors for the detection of SSF6 decomposition products under PD conditions. AB - Sulfur hexafluoride (SF6) gas decomposition results from the energy produced by partial discharge (PD). The detection of SO2 and H2S content, as important characteristic components of the decomposition products, is significant in the determination of the insulation level of SF6 gas and the inside insulation faults of gas-insulated equipment. A number of gas sensors use carbon nanotubes (CNTs). However, the applications of these sensors are limited by their low intrinsic sensitivity. In this paper, an adsorbent-mixed carbon nanotube gas sensor is proposed to improve the detection of SO2 and H2S concentrations. The sensitivity of adsorbent-mixed carbon nanotube gas sensors to SO2 and H2S at 100 ppm was investigated experimentally. The effect of the mixing ratio on the gas sensitivity characteristic and mechanism of response was also studied. The results show that compared with intrinsic CNTs gas sensors, the gas sensor featuring adsorbent-mixed CNTs has significantly higher sensitivity and responsiveness to SO2 and H2S. The resistance-change rate of SO2 and H2S increased to 33.7% and 50.9% from 0.96% and 12.9%, respectively. Moreover, the resistance-change rate and gas concentration satisfy a linear relationship. The sensor has good repeatability and stability. PMID- 24212120 TI - A new approach for improving reliability of personal navigation devices under harsh GNSS signal conditions. AB - In natural and urban canyon environments, Global Navigation Satellite System (GNSS) signals suffer from various challenges such as signal multipath, limited or lack of signal availability and poor geometry. Inertial sensors are often employed to improve the solution continuity under poor GNSS signal quality and availability conditions. Various fault detection schemes have been proposed in the literature to detect and remove biased GNSS measurements to obtain a more reliable navigation solution. However, many of these methods are found to be sub optimal and often lead to unavailability of reliability measures, mostly because of the improper characterization of the measurement errors. A robust filtering architecture is thus proposed which assumes a heavy-tailed distribution for the measurement errors. Moreover, the proposed filter is capable of adapting to the changing GNSS signal conditions such as when moving from open sky conditions to deep canyons. Results obtained by processing data collected in various GNSS challenged environments show that the proposed scheme provides a robust navigation solution without having to excessively reject usable measurements. The tests reported herein show improvements of nearly 15% and 80% for position accuracy and reliability, respectively, when applying the above approach. PMID- 24212121 TI - A coaxial cable Fabry-Perot interferometer for sensing applications. AB - This paper reports a novel coaxial cable Fabry-Perot interferometer for sensing applications. The sensor is fabricated by drilling two holes half-way into a coaxial cable. The device physics was described. The temperature and strain responses of the sensor were tested. The measurement error was calculated and analyzed. PMID- 24212122 TI - Monitoring the evaporation of fluids from fiber-optic micro-cell cavities. AB - Fiber-optic sensors provide remote access, are readily embedded within structures, and can operate in harsh environments. Nevertheless, fiber-optic sensing of liquids has been largely restricted to measurements of refractive index and absorption spectroscopy. The temporal dynamics of fluid evaporation have potential applications in monitoring the quality of water, identification of fuel dilutions, mobile point-of-care diagnostics, climatography and more. In this work, the fiber-optic monitoring of fluids evaporation is proposed and demonstrated. Sub-nano-liter volumes of a liquid are applied to inline fiber optic micro-cavities. As the liquid evaporates, light is refracted out of the cavity at the receding index boundary between the fluid and the ambient surroundings. A sharp transient attenuation in the transmission of light through the cavity, by as much as 50 dB and on a sub-second time scale, is observed. Numerical models for the transmission dynamics in terms of ray-tracing and wavefront propagation are provided. Experiments show that the temporal transmission profile can distinguish between different liquids. PMID- 24212123 TI - Social support for parents of deaf children: moving toward contextualized understanding. AB - In light of claims that social support needs to be defined within specific context, we conducted a metasynthesis to identify ways that social support has been studied and contextualized in research focused on hearing parents of children with hearing loss. A literature search of published articles was conducted to identify research studies related to support and hearing parents of children with hearing loss. Our search yielded 108 items from Psycinfo and 154 items from Web of Science; 26 studies met our inclusion criteria. Our analyses involved summary and integration of information regarding research methods, guiding theoretical frameworks, and findings in relation to diverse support contexts. We found that it is the multidimensionality of social support and its specific functions, individually and in combination, that are particularly relevant in informing family-centered service provision. Further understanding of the multidimensional and dynamic nature of support could occur through investigation of diverse functions of support within and across ecological contexts. Findings from this study contributed to a descriptive framework that can be used to explore the multidimensionality of support; facilitate use of methods that assess specific support functions; and also inform the development of interventions that are responsive and match the needs of parents. PMID- 24212126 TI - Seven novel coordination polymers constructed by rigid 4-(4-carboxyphenyl) terpyridine ligands: synthesis, structural diversity, luminescence and magnetic properties. AB - Seven coordination polymers, namely [Mn(4-cptpy)2]n (1), [Co(4-cptpy)2]n (2), [Mn3(4-cptpy)6(H2O)]n.2nH2O (3), [Co(4-cptpy)(HCOO)(H2O)]n.nDMF (4), [Zn2(4 Hcptpy)2Cl4]n.2nC2H5OH.nH2O (5), [Co4(3-cptpy)4(HCOO)4(H2O)2]n (6), and [Mn(3 cptpy)2]n (7) (4-Hcptpy = 4-(4-carboxyphenyl)-4,2':6',4''-terpyridine; 3-Hcptpy = 4-(4-carboxyphenyl)-3,2':6',3''-terpyridine), have been synthesized under hydro(solvo)thermal conditions and structurally characterized. A general solvothermal method is proposed for preparing carboxylate complexes in DMF solution without any basic additive. 1 and 2 possess isostructural 3D metal organic frameworks containing nanosized cavities. 3 is a beautiful 2D coordination polymer assembled by flower-like Mn3(4-cptpy)6(H2O) subunits. 4 and 6 both display 2D polymeric networks constructed from 4/3-cptpy(-) ligands, in which the formate ligands originate from the hydrolysis of DMF. 5 is a 1D 2(1) helical chain polymer. 7 shows a 2D network with a (3.6) two-nodal kgd topology. 4/3-Hcptpy ligands display seven types of coordination modes. The zinc complex 5 emits strong violet luminescence. 1 and 2 are both thermally stable below 440 degrees C and exhibit antiferromagnetic interactions. PMID- 24212125 TI - Synthesis, ex vivo and in silico studies of 3-cyano-2-pyridone derivatives with vasorelaxant activity. AB - An efficient and simple synthesis of 3-cyano-2-pyridone derivatives (6a-f) through 3,4-dihydropyridin-2-one oxidation process is described. A greener method to synthesize 3,4-dihydropyridin-2-one has also been developed by rearranging 4H pyran (4a-f) derivatives in aqueous medium applying H2SO4 as the catalyst source and microwave irradiation. The vasorelaxant activity of 3-cyano-2-pyridone derivatives (6a-f) was proved on isolated thoracic aorta rat rings with and without endothelium (+E and -E, respectively) pre-contracted with noradrenaline (0.1 MUM). All compounds exhibited significant concentration-dependent and endothelium-independent vasorelaxant effects being the nitro derivatives (6a and f) and compound 6d the most potent with EC50 of 7, 4.4 and 5 MUM, respectively. Finally, a previously described 3D model of the central pore of human L-type calcium channel (LCC), modified to be on agreement with NCBI sequence NP_005174.2 for subunit alpha-1F isoform 1, was used to dock most active compounds. 6a, d and f lowest affinity energy structures were found docked in the same cavity conformed by IS6, IS5, IP and IIS6 helices. Nifedipine lowest energy structure was found in the cavity formed by IIS6, IIS5, IIP and IIIS6. Although nifedipine docked in a different cavity, the superposition of both, allowed us to observe that they were almost the same cavities, indicating that there exist subtle steric differences that lead to a different docking for nifedipine. All compounds docked with similar free energy of binding. PMID- 24212124 TI - Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors. AB - PURPOSE: This study aimed to examine mediators of fatigue response to an exercise intervention for breast cancer survivors in a pilot randomized controlled trial. METHODS: Postmenopausal breast cancer survivors (n = 46; <=stage 2), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3 month exercise intervention (160 min.wk of moderate-intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months. RESULTS: The exercise intervention effect sizes for fatigue were as follows: fatigue intensity d = 0.30 (P = 0.34), interference d = -0.38 (P = 0.22), and general fatigue d = -0.49 (P = 0.13). Using the Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin 6 (IL-6) (82%), IL-10 (94%), IL-6/IL-10 (49%), and tumor necrosis factor-alpha (TNF-alpha):IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (-88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%), whereas IL-10 and pro-anti-inflammatory cytokine ratios increased the relationship between intervention and interference (-25% to -40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%), with IL-10 (-40%) and IL-6/IL-10 (-11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barrier interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention. CONCLUSIONS: Biobehavioral factors mediated and enhanced intervention effects on fatigue, whereas psychosocial factors predicted fatigue response. Further study is warranted to confirm our results and to improve understanding of relationships that mediate and strengthen the intervention fatigue association. PMID- 24212127 TI - Hiking on the potential energy surface of a functional tyrosinase model- implications of singlet, broken-symmetry and triplet description. AB - The singlet, open-shell singlet and triplet potential energy surfaces (PES) for the peroxo state of a catalytic functional tyrosinase model have been investigated by density functional theory calculations. The broken-symmetry solution exhibits considerable stabilisation over the whole PES but the importance of the triplet state is unravelled as well. PMID- 24212128 TI - Comparison of bamboo green, timber and yellow in sulfite, sulfuric acid and sodium hydroxide pretreatments for enzymatic saccharification. AB - The response and behavior of bamboo green, timber, and yellow of moso bamboo (Phyllostachys heterocycla) to three pretreatments, sulfite (SPORL), dilute acid (DA), and alkali (NaOH), were investigated and compared with varied chemical loadings at 180 degrees C for 30 min with a 6.25:1 (v/w) liquor-to-bamboo ratio. All the pretreatments improved the enzymatic digestibility of bamboo substrates. Under the investigated conditions, the DA pretreatment achieved better enzymatic digestibility, but had lower sugar recovery yield, and formed more fermentation inhibitors. The results suggested that the SPORL pretreatment be able to generate more readily digestible bamboo substrate with higher sugar yield and fewer fermentation inhibitors than the corresponding DA pretreatment if hemicelluloses are sufficiently removed by adding more acid to bring down the pretreatment pH. Bamboo timber had higher sugar content and better enzymatic digestibility and therefore was a better feedstock for bioconversion than bamboo green and yellow. PMID- 24212129 TI - Phosphate transporter mediated lipid accumulation in Saccharomyces cerevisiae under phosphate starvation conditions. AB - In the current study, when phosphate transporters pho88 and pho86 were knocked out they resulted in significant accumulation (84% and 43%) of triacylglycerol (TAG) during phosphate starvation. However in the presence of phosphate, TAG accumulation was only around 45% in both pho88 and pho86 mutant cells. These observations were confirmed by radio-labeling, fluorescent microscope and RT-PCR studies. The TAG synthesizing genes encoding for acyltransferases namely LRO1 and DGA1 were up regulated. This is the first report for accumulation of TAG in pho88Delta and pho86Delta cells under phosphate starvation conditions. PMID- 24212130 TI - Study on anaerobic treatment of hazardous steel-mill waste rolling oil (SmWRO) for multi-benefit disposal route. AB - Steel-mill waste rolling oil (SmWRO) is considered as hazardous substance with high treatment and disposal fees. Anaerobic process could not only transform the hazardous substance into activated sludge, but also generate valuable biogas. This study aimed at studying the biochemical methane potential of SmWRO under inoculum to substrate VS ratios (ISRs) of 0.25, 0.5, 1, 1.5, 2 and 3 using septic tank sludge as inoculum in mesophilic and thermophilic conditions, with blank tests for control. Specific biogas yield (mL/g VS(added)), net biogas yield (mL/g VS(removed)) and VS removal were analyzed. The ANOVA results indicated great influence of ISR and temperature on studied parameters. ISR of 1.5 at 55 degrees C and ISR of 1.5 and 2 at 35 degrees C were suggested with the highest specific biogas yield (262-265 and 303mL/g VS(added)). Kinetic analysis showed that Gompertz model fit the experimental data best with the least RMSE and largest R(2). PMID- 24212131 TI - Production of bacterial cellulose by Gluconacetobacter hansenii CGMCC 3917 using only waste beer yeast as nutrient source. AB - In order to improve the use of waste beer yeast (WBY) for bacterial cellulose production by Gluconacetobacter hansenii CGMCC 3917, a two-step pre-treatment was designed. First WBY was treated by 4 methods: 0.1M NaOH treatment, high speed homogenizer, ultrasonication and microwave treatment followed by hydrolysis (121 degrees C, 20 min) under mild acid condition (pH 2). The optimal pre-treatment conditions were evaluated by the reducing sugar yield after hydrolysis. 15% WBY treated by ultrasonication for 40 min had the highest reducing sugar yield (29.19%), followed by NaOH treatment (28.98%), high speed homogenizer (13.33%) and microwaves (13.01%). Treated WBY hydrolysates were directly supplied as only nutrient source for BC production. A sugar concentration of 3% WBY hydrolysates treated by ultrasonication gave the highest BC yield (7.02 g/L), almost 6 times as that from untreated WBY (1.21 g/L). Furthermore, the properties of the BC were as good as those obtained from the conventional chemical media. PMID- 24212133 TI - Expression of tumor necrosis factor-related apoptosis-inducing ligand death receptors DR4 and DR5 in human nonmelanoma skin cancer. AB - Death receptors 4 and 5 (DR4 and DR5) are cell surface receptors that when activated by their ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in most cancer cells but not in normal cells. Currently, it remains unclear whether DR4 and DR5 are involved in immune surveillance against nonmelanoma skin cancer (NMSC) progression. The aim of this study was to investigate the expression of DR4 and DR5 in NMSC and relate the results to the established clinicopathologic prognostic factors. This study was conducted on about 80 skin specimens from patients with NMSC (40 basal cell carcinoma and 40 squamous cell carcinoma) and diagnosed and confirmed by biopsy. Immunohistochemical analysis for DR4 and DR5 was carried out on formalin-fixed paraffin-embedded sections of skin tissues using avidin-biotin peroxidase method. Significant expression of both DR4 and DR5 was observed in NMSC cases. There was statistically significant association between DR4 and DR5 expression in squamous cell carcinoma and each of tumor site and lymph node metastasis. There was statistically significant association between DR4 expression in basal cell carcinoma and histopathologic subtypes (high expression in nodular type) and between DR5 expression and tumor site (high expression in sun-exposed area). In conclusion, expression of TRAIL receptors that mediate extrinsic apoptotic pathway in NMSC may be suggestive of a reassessment of the suitability of TRAIL based strategy in future NMSC therapies. PMID- 24212132 TI - Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke. AB - Accumulating evidence shows that post-ischemic inflammation originated by Toll like receptors (TLR) plays critical roles in ischemic stroke. However, the functions of other innate immune receptors are poorly understood in cerebral ischemia. Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells. In the present study, we showed that Mincle, its ligand SAP130, and its downstream phospho-Syk/Syk were upregulated after ischemia, and that Mincle is expressed in immune and non-immune cells in the ischemic brains of mice and human. We treated mice with piceatannol, a Syk inhibitor, and consequently the infarct volume and swelling were suppressed by piceatannol. The levels of phospho-Syk, MMP9 and ICAM 1 were downregulated, and the level of Claudin5 was uplegurated in piceatannol treated groups. These data indicate that innate immune system, such as Mincle and Syk plays a pivotal role in the pathogenesis after the ischemia and reperfusion. PMID- 24212134 TI - Imperfect coordination chemistry facilitates metal ion release in the Psa permease. AB - The relative stability of divalent first-row transition metal ion complexes, as defined by the Irving-Williams series, poses a fundamental chemical challenge for selectivity in bacterial metal ion acquisition. Here we show that although the substrate-binding protein of Streptococcus pneumoniae, PsaA, is finely attuned to bind its physiological substrate manganese, it can also bind a broad range of other divalent transition metal cations. By combining high-resolution structural data, metal-binding assays and mutational analyses, we show that the inability of open-state PsaA to satisfy the preferred coordination chemistry of manganese enables the protein to undergo the conformational changes required for cargo release to the Psa permease. This is specific for manganese ions, whereas zinc ions remain bound to PsaA. Collectively, these findings suggest a new ligand binding and release mechanism for PsaA and related substrate-binding proteins that facilitate specificity for divalent cations during competition from zinc ions, which are more abundant in biological systems. PMID- 24212135 TI - Dynamic ligand binding dictates partial agonism at a G protein-coupled receptor. AB - We present a new concept of partial agonism at G protein-coupled receptors. We demonstrate the coexistence of two functionally distinct populations of the muscarinic M2 receptor stabilized by one dynamic ligand, which binds in two opposite orientations. The ratio of orientations determines the cellular response. Our concept allows predicting and virtually titrating ligand efficacy, which opens unprecedented opportunities for the design of drugs with graded activation of the biological system. PMID- 24212138 TI - Experimental assessment of the coincidence summing corrections in gamma-ray spectrometry of bulk samples. AB - This work presents an experimental approach for estimation of the true coincidence-summing (TCS) correction for volume sources on the basis of TCS dependence on the source-to-detector distance. Firstly, it is shown that the TCS dependence on the source-to-detector distance can be linearized for point source geometry. If this linear dependence is established then TCS correction for an arbitrary source-to-detector distance can be obtained. In the case of a volume source a representative parameter d(V) can be formulated as the distance at which the point-source summing effect is the same as the one for the volume-source. Then if the TCS dependence on the source-to-detector distance is established for the point-source case and the volume-source d(V)-value is known, the TCS correction corresponding to the volume-source measuring geometry can be estimated. Experimental method and results are presented in the work too. PMID- 24212137 TI - Prospective associations between inflammatory and hemostatic markers and physical functioning limitations in mid-life women: Longitudinal results of the Study of Women's Health Across the Nation (SWAN). AB - BACKGROUND: Due to the public health burden of age-related declines in physical functioning, it is important to identify targets for intervention for the prevention of functional decline. We prospectively examined whether higher levels of inflammatory and hemostatic markers (high-sensitivity C-reactive protein (hs CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA-ag), fibrinogen, and Factor VIIc (FVIIc)) were prospectively associated with reporting greater limitations in perceived physical functioning, and explored potential racial differences in the associations, in a multi-ethnic sample of mid-life women. METHODS: Women (45-56 years) in the Study of Women's Health Across the Nation who completed the physical functioning scale of the Medical Outcome Short Form (SF-36) at follow-up visits 4, 6, or 8 and had inflammatory/hemostatic measures in the preceding year were included (n=2296). The continuous SF-36 physical function score was categorized as: no limitation (86-100 points), some limitation (51-85 points), and substantial limitation (0-50 points). Physical function category at time t was modeled a function of each biomarker, separately, at time t-1 using ordinal generalized estimating equations. RESULTS: After adjusting for age, race/ethnicity, body size, sociodemographic, medical and lifestyle factors, higher levels of tPA-ag and hs CRP were associated with subsequently reporting greater limitations in physical functioning, although the latter was only marginally significant (p=0.13). For each standard deviation (SD) increase in logtPA-ag, the odds of some or substantial limitations was 1.18 (95%CI 1.09,1.27); for each SD increase in loghs CRP, the odds of some or substantial limitation was (1.08, 95%CI 0.98,1.19). In African American women only, higher fibrinogen levels were associated with subsequently reporting greater limitations (OR=1.30, 95%CI 1.13,1.50, for each one SD increase in fibrinogen). CONCLUSIONS: Higher levels of inflammatory and hemostatic markers were prospectively associated with greater limitations in perceived physical functioning in mid-life women. PMID- 24212139 TI - Simple segmental hair analysis for alpha-pyrrolidinophenone-type designer drugs by MonoSpin extraction for evaluation of abuse history. AB - For detection of a history of drug abused, we developed a simple method for extracting pyrrolidinophenone-type designer drugs in human hair by using a MonoSpin((r)) C18 column. Target drugs were extracted from a single alkaline digested hair segment (length, 10mm; weight, ca 0.1mg). The analytes extracted were then analyzed by high-performance liquid chromatography-mass spectrometry without evaporation of the eluent after MonoSpin extraction. Linearity from 0.5 to 500ng/mg was observed for all the tested drugs using an internal standard method (correlation coefficients >0.998) and the limit of detection was 0.2ng/mg. The recoveries were between 0.7 and 11.1%. The coefficients for intraday and interday variations at 4, 40, 200, and 400ng/mg in hair were between 0.7 and 11.1%. This method was successfully applied to the identification of these designer drugs in segmented human hair from drug abusers and indicated their history of drug abuse. The results were consistent with the patients' statements, indicating that this rapid method can be used to detect a history of drug abuse. PMID- 24212140 TI - Capillary electrophoresis-mass spectrometry for direct determination of urinary modified nucleosides. Evaluation of synthetic urine as a surrogate matrix for quantitative analysis. AB - This work describes the development of a fast and reliable method based on capillary zone electrophoresis coupled with electrospray ionization-mass spectrometry (CZE-ESI-MS) for the determination of modified nucleosides in untreated human urine. The target compounds were guanine, 1-methyl-guanine, 7 methyl-guanine, 9-methyl-guanine, adenosine, 1-methyl-adenosine, cytidine, guanosine, 7-methyl-guanosine. As internal standards, ribose-2-(13)C-adenosine and 8-(13)C-guanine were used. The CZE separation was carried out in acidic medium (pH 2.5). MS detection with a single quadrupole, with ESI operating in positive-ion mode, was optimized. For the analysis of urine samples, owing to the endogenous character of these analytes different quantification strategies were explored. The standard additions method, matrix-matched calibration in synthetic urine and calibration in pure aqueous medium were compared in order to evaluate the endogenous levels of these compounds in human urine. The results obtained showed that calibration in synthetic urine as a surrogate matrix was an appropriate alternative to the method of standard additions for the accurate quantitation of compounds such as guanine, 1-methyl-guanine, 7-methyl-guanine, adenosine, 1-methyl-adenosine and cytidine by CE-ESI-MS directly in the urine matrix; values in the range 0.1MUg/mL for cytidine and 6.4MUg/mL for 7mGua, as the lowest and the highest level, were found in untreated urine from healthy volunteers. These results were confirmed by LC-MS/MS detection. It can be concluded that the electrophoretic CZE-ESI-MS methodology offers a valid and reliable alternative for the determination of urinary nucleosides at naturally occurring levels in healthy individuals. PMID- 24212136 TI - Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. AB - Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS. PMID- 24212141 TI - A simple sample preparation approach based on hydrophilic solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry for determination of endogenous cytokinins. AB - Cytokinins (CKs), a vital family of phytohormones, play important roles in the regulation of shoot and root development. However, the quantification of CKs in plant samples is frequently affected by the complex plant matrix. In the current study, we developed a simple, rapid and efficient hydrophilic interaction chromatography-solid phase extraction (HILIC-SPE) method for CKs purification. CKs were extracted by acetonitrile (ACN) followed by HILIC-SPE (silica as sorbents) purification. The extraction solution of plant samples could be directly applied to HILIC-SPE without solvent evaporation step, which simplified the analysis process. Moreover, with HILIC chromatographic retention mechanism, the hydrophobic co-extracted impurities were efficiently removed. Subsequently, CKs were separated by RPLC, orthogonal to the HILIC pretreatment process, and detected by tandem mass spectrometry. The method exhibits high specificity and recovery yield (>77.0%). Good linearities were obtained for all eight CKs ranging from 0.002 to 100ngmL(-1) with correlation coefficients (r) higher than 0.9927. The limits of detection (LODs, signal/noise=5) for the CKs were between 1.0 and 12.4pgmL(-1). Reproducibility of the method was evaluated by intra-day and inter day measurements and the results showed that relative standard deviations (RSDs) were less than 10.5%. Employing this method, we successfully quantified six CKs in 20mg Oryza sativa leaves and the method was also successfully applied to Brassica napus (flower and leaves). PMID- 24212142 TI - Simultaneous determination of eight illegal dyes in chili products by liquid chromatography-tandem mass spectrometry. AB - A sensitive and accurate method based on the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous determination of eight illegal synthetic dyes (Sudan (I-IV), Para Red, Rhodamine B, Chrysoidin and Auramine O) in chili products. A simple sample treatment procedure entailing the use of an extraction step with acetonitrile/H2O (9/1) without further cleanup was developed. HPLC was performed on a C18 column using a multistep gradient elution with 5mM ammonium acetate (pH 3.0 with formic acid) and methanol as the mobile phase. Mass spectral acquisition was done in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Linear calibrations were obtained with correlation coefficients R(2)>0.99. Limit of detection (LOD) and limit of quantification (LOQ) for the studied dyes were in the ranges of 0.05 0.6MUgkg(-1) and 0.3-3.0MUgkg(-1) depending on matrices, respectively. The recoveries of the eight synthetic dyes in five matrices ranged from 70.5% to 119.2%. The intra- and inter-day precisions (RSDs) were between 2.3-15.8% and 5.7 15.6%, respectively. The applicability of the method to the determination of eight banned dyes in chili products was demonstrated. PMID- 24212144 TI - Assessing mHealth: opportunities and barriers to patient engagement. PMID- 24212143 TI - The profile of bile acids and their sulfate metabolites in human urine and serum. AB - The role of sulfation in ameliorating the hepatotoxicity of bile acids (BAs) in humans remains unknown due to the lack of proper analytical methods to quantify individual BAs and their sulfate metabolites in biological tissues and fluids. To this end, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to characterize the detailed BA profile in human urine and serum. The limit of quantification was 1ng/mL and baseline separation of all analytes was achieved within in a run time of 32min. The method was validated over the dynamic range of 1-1000ng/mL. The LC-MS/MS method was more accurate, precise, and selective than the commercially available kits for the quantification of sulfated and unsulfated BAs, and the indirect quantification of individual sulfated BAs after solvolysis. The LC-MS/MS method was applied to characterize the BA profile in urine and serum of healthy subjects. Thirty three percent of serum BAs were sulfated, whereas 89% of urinary BAs existed in the sulfate form, indicating the role of sulfation in enhancing the urinary excretion of BAs. The percentage of sulfation of individual BAs increased with the decrease in the number of hydroxyl groups indicating the role of sulfation in the detoxification of the more hydrophobic and toxic BA species. Eighty percent of urinary BAs and 55% of serum BAs were present in the glycine amidated form, whereas 8% of urinary BAs and 13% of serum BAs existed in the taurine-amidated form. PMID- 24212145 TI - Global health at home: a student-run community health initiative for refugees. AB - Free, student-run health initiatives for refugees fill a gap in needed health services and prepare medical students for understanding cross-cultural and systems-based medical practice. PMID- 24212146 TI - Community health centers and the patient-centered medical home: challenges and opportunities to reduce health care disparities in America. AB - Health care disparities pose an ongoing challenge to the nation. The patient centered medical home (PCMH) model presents a unique opportunity for community health centers (CHCs) to improve the health of medically underserved communities and reduce health care disparities. Community health centers face ongoing financial and operational challenges, but are well positioned to adopt the PCMH. Health centers have experience collaborating on quality improvement initiatives and possess a strong organizational structure. The culture of CHCs emphasizes cultural competence, team work, and patient-centrism, and is well-aligned with the PCMH model. However, CHCs need more support to make fundamental changes in processes and practice culture. Many of these changes require substantial redesigns that can challenge even the most innovative practices. State and federal policy should focus on providing training, guidance, and payment mechanisms that support PCMH. Taking these steps, the U.S. can achieve the goal that every American receives patient-centered care that is equitable, affordable, and effective. PMID- 24212147 TI - Understanding the health transitions of immigrants to Canada: research priorities. AB - Understanding changes in the health of immigrants has been an important area of research in Canadian public health. Recent years have seen important developments, with studies moving away from what might be called 'sick immigrant' versus 'healthy immigrant' debates towards analyzing transitions and how they are influenced by a diverse set of social determinants. The release of data from all three waves of the Longitudinal Survey of Immigrants to Canada has also spurred new theoretical understandings of why immigrants' initial health advantage is lost over time, with the experience of discrimination becoming an increasingly important predictor. Three research priorities are emerging as particularly important in this area. These are the need for multilevel analyses that incorporate contextual effects, the need for comparative international studies, and the need to refine the conceptualization of race/ethnicity to take advantage of developments in social theory. PMID- 24212148 TI - The health promise of Promise Neighborhoods. AB - The Promise Neighborhoods initiative from the U.S. Department of Education offers grant funding to develop innovative educational and community support programs in distressed communities. Inspired by the success of the Harlem Children's Zone (HCZ), this initiative encourages similarly pioneering approaches to assist low income children attain academic and social success. An increasing body of evidence suggests that health benefits accrue when youth are immersed in nurturing educational environments. This article summarizes key evidence for this phenomenon, as well as theories that suggest that Promise Neighborhoods can have as great an effect on health as they do on educational achievement. PMID- 24212149 TI - National culturally and linguistically appropriate services standards--mandates or not? AB - The U.S. Department of Health and Human Services' Office of Minority Health (OMH) promotes National Standards for Culturally and Linguistically Appropriate Services. According to the Office, four of these standards are "mandates" that are considered federal requirements for all recipients of federal funds. These standards focus on increasing language access to health care services for limited English proficient (LEP) people. Relying on this statement, multiple organizations, scholars and advocates promote these mandates in their communities. However, the DHHS Office of Inspector General stated in a 2010 report that these standards are only voluntary and not mandated. This contradiction deserves the attention of public health advocates for LEP people. This article seeks to clarify this contradiction so that public health advocates and experts can provide accurate information to people they serve and consider whether they should work with to develop truly mandatory language access standards as a condition of federal funding. PMID- 24212150 TI - Improving access to care for uninsured patients at an academic medical center: The Access Partnership. AB - Uninsured individuals face great challenges in accessing both primary and specialty care. The Access Partnership (TAP) is a novel collaboration between primary and specialty care providers at an urban academic medical center to provide care coordination and facilitate access to specialty services for uninsured patients. We reviewed administrative data and performed phone surveys of the 213 patients who entered the program over a one-year period. Specialty care visit attendance was analyzed from administrative data for these patients. We then surveyed patients by phone (60% response rate). Patient-reported access to care and satisfaction with care were significantly higher after TAP (33% vs. 87%, p<0.001 and 41% vs. 91%, p<0.001, respectively). 89% of referrals were completed within 90 days among TAP patients, a rate similar to studies involving insured patients. TAP enrollment was associated with significantly decreased patient-reported barriers to specialty care as well as improved access to and satisfaction with care. PMID- 24212151 TI - Combating slavery in the 21st century: the role of emergency medicine. AB - Human trafficking (HT) victims may present to emergency departments (ED) as patients, but are infrequently identified. To address this issue, we developed and piloted a training intervention for emergency providers on HT and how to identify and treat these patients. Included in the intervention participants were emergency medicine residents, ED attendings, ED nurses, and hospital social workers. Prior to the intervention, 4.8% felt some degree of confidence in their ability to identify and 7.7% to treat a trafficked patient. After the 20-minute intervention, 53.8% felt some degree of confidence in their ability to identify and 56.7% care for this patient population. Because this problem is global, we created a Website that includes an instructive toolkit and an interactive course for self-learning and/or assessment. This intervention will give ED providers the tools they need to assess and treat a patient who might be a victim of human trafficking. PMID- 24212152 TI - Healthy Heart, Healthy Family: a NHLBI/HRSA collaborative employing community health workers to improve heart health. AB - Kokua Kalihi Valley, a federally qualified health center in Hawaii, collaborated with the National Heart, Lung, and Blood Institute to test the efficacy of community health workers (CHWs) to deliver the Healthy Heart, Healthy Family curriculum to low-income Filipinos with cardiovascular disease (CVD) risk factors. At 12 months, significant improvements were seen in health behaviors, knowledge, and self-efficacy in managing chronic diseases. We also observed decreases in total cholesterol from 186.25 mg/dl to 170.88 mg/dl (p=.001), low density lipoprotein from 114.43 mg/dl to 103.04 mg/dl (p=.013), and fasting blood glucose from 117.95 mg/dl to 109.07 mg/dl (p=.034). Although these changes were statistically significant, they are small and not clinically meaningful in reducing CVD risk. The high-density lipoprotein was 3.3 mg/dl lower (worse) at 12 months (p=.003), mean values for blood pressure, BMI, and waist circumference increased. Community health workers can be trained to deliver evidence-based curricula that improve health behaviors and increase self-efficacy in managing chronic diseases. PMID- 24212153 TI - Prevalence of heart disease and its risk factors related to age in Asians, Pacific Islanders, and Whites in Hawai'i. AB - OBJECTIVE: To examine disparities in disease prevalence related to age and race/ethnicity. Study design. Retrospective observational study. METHODS: Eligible population included enrollees with largest insurer in Hawai'i. Chronic diseases were identified from claims data (1999-2009) based on algorithms including diagnostic codes and pharmaceutical utilization. Relative risk of heart disease and its risk factors were calculated for Native Hawaiians and Asian sub groups by age. RESULTS: Prevalence of heart disease and its risk factors differed substantially by age and race/ethnicity. Native Hawaiians and Filipinos had higher rates of hypertension and diabetes; Asians had highest rates of hyperlipidemia. Whites had the lowest prevalence of risk factors yet their risk of heart disease equaled other groups. CONCLUSION: Prevalence curves began diverging at age 30 for risk factors and age 40 for heart disease. This suggests approaches to reduce the burden of disease for vulnerable groups need to begin in early adulthood if not sooner. PMID- 24212154 TI - Patient and provider factors associated with colorectal cancer screening in safety net clinics serving low-income, urban immigrant Latinos. AB - BACKGROUND: Latinos have lower colorectal cancer screening rates than Whites. METHODS: We reviewed a random sample of charts between July 2009 and February 2010 of safety-net clinic of 840 immigrants (50 years and older) from Central and South America receiving care. Logistic regression evaluated associations of ever vs. never screening, patient and physician factors. RESULTS: Ever screening rates were 24.5%, and only 17% of charts noted a physician screening recommendation. However, the odds of screening were 9.89 times higher (95% CI: 6.25-15.64, p<.001) among patients with a physician recommendation vs. those without, considering covariates. The odds of screening were 0.61 times lower (95% CI: 0.40 0.92, p=.02) in patients with a body mass index >= 30 vs. <30. CONCLUSIONS: While rates were low, determinants of screening were similar in this Latino subgroup to those reported in other Latino and non-Latino populations. Low rates of documented physician screening recommendations may indicate a potential missed opportunity for cancer control in safety-net clinics. PMID- 24212155 TI - An assessment of malaria curative services in Ijara district, a remote community in the North-Eastern province of Kenya. AB - INTRODUCTION: Malaria is a major public health problem in Kenya and there is need to strengthen malaria control activities at the district level. METHODS: As part of this, an assessment of malaria curative services offered in health facilities in terms of health care material availability and the case management skills of the health workers was conducted in Ijara district. A questionnaire was administered to the health workers. Observation and physical inspection of malaria health care material and perusal of relevant documents were also carried out in all health facilities in 2011. RESULTS: All health facilities had the recommended drugs, though only 90% of facilities had quinine injection. All facilities lacked Rapid Diagnostic Tests, Adverse Drug Reaction reporting forms, and poor quality medicine forms. CONCLUSIONS: There is need to equip the health workers with up-to-date case management skills and to provide rapid diagnostic tests. PMID- 24212156 TI - Applying the Social Ecological Model to evaluate a demonstration colorectal cancer screening program in Louisiana. AB - OBJECTIVE: Lack of health insurance is correlated with noncompliance in colorectal cancer screening. Louisiana ranks 48th among all states in residents with health insurance. This paper describes initial results of Louisiana's first statewide colorectal cancer screening program. METHODS: The program enhanced screening capacity of state hospitals by providing fecal immunochemical tests (FITs), colonoscopes, and funded patient navigators. The Social Ecological Model (SEM) was used as the framework for the program. RESULTS: Patient navigators distributed 975 FITs to adults 50 to 64 years (21% men, 78% women).The overall return rate was 66%. There was no association among return rates, race, or gender. Participants who were previously screened (10.7%) were more likely to return their FIT. DISCUSSION: The combination of patient navigation and providing patients with an easy-to-use CRC screening option proved to be an effective method that potential colorectal cancer screening programs can deploy in similar populations of un- and under-insured adults. PMID- 24212157 TI - Effectiveness of outreach to patients with diabetes who have fallen out of regular care at a federally qualified health center. AB - Re-engaging patients who have fallen out of regular care is a challenge for all primary care practices, but especially for federally qualified health centers (FQHCs). We implemented and evaluated a system of proactive telephone and mail outreach within an FQHC serving a predominantly Latino and Spanish-speaking population for patients with diabetes who had not had a visit to the health center for at least six months. The primary study outcome was the proportion of patients who completed a follow-up visit within three months of the outreach. We also examined patient characteristics associated with completing a follow-up visit. Of 208 patients eligible for outreach, 24% (n = 49) completed a follow-up visit. Thirty-six percent (n = 74) had a disconnected or incorrect phone number, 16% (n = 34) were not reached within three phone call attempts, and 20% (n = 22) of letters mailed were returned to sender. Future efforts to re-engage patients in diabetes care should examine shorter intervals before outreach and other outreach strategies. PMID- 24212158 TI - Over-the-counter medication purchase and use by blind consumers. AB - Little is known regarding consumption of over-the-counter (OTC) medications by the blind. They may face difficulty while accessing information from OTC medication labels. This exploratory, cross-sectional study was designed to determine blind consumers' attitude and purchase behavior towards OTC medications and use of low-vision tools while using these medications. PMID- 24212159 TI - Impact of student-run clinics on preclinical sociocultural and interprofessional attitudes: a prospective cohort analysis. AB - INTRODUCTION: Descriptive studies suggest student-run clinics (SRCs) positively affect preclinical students' sociocultural and interprofessional attitudes, but few studies use validated measures. METHODS: In a pre-post design, first-year medical, nursing, and pharmacy students who did and did not participate in SRCs completed demographic and open-ended questions, as well as two validated surveys, the Sociocultural Attitudes in Medicine Inventory (SAMI) and Readiness for Interprofessional Learning Scale (RIPLS), at the beginning and end of the year. RESULTS: With 68% (n=182/267) matched surveys we found no significant differences between groups over time (SAMI p=.53, RIPLS p>=.28 for each subcategory). However, of SRC participants, 99% reported commitment to the underserved and 57% reported improved interprofessional attitudes. DISCUSSION: Students participating in SRCs perceive positive benefits, but do not score differently from those who do not. The SRC experiences may not be frequent enough to affect these measures, particularly since our students were high-scoring upon entry. PMID- 24212160 TI - Need, availability, and quality of interpreter services among publicly insured Latino, Hmong, and Somali individuals in Minnesota. AB - Limited English proficiency (LEP) is a common barrier that negatively affects access to health care and quality of care. Prior studies have examined interpreter services as a means of ameliorating LEP, but have focused on Spanish language services, largely overlooking comparisons with other, less-established ethnic groups. Furthermore, few if any studies have assessed the quality of interpreter services provided. Data come from 2,489 Hispanic/Latino, Hmong, and Somali enrollees of public health insurance programs in Minnesota. We employ weighted, regression-adjusted comparisons of enrollee-reported need and availability of interpreters, access to professional and consistent interpreters, and problems with quality of interpreter-assisted communication. Compared with Latinos, Hmong and Somali enrollees reported greater needs and more communication problems, Somali enrollees reported lower availability, and Hmong enrollees reported lower access to professional interpreters. Further training of interpreters for relatively less-established ethnic groups is needed to increase availability of professional, high-quality communication among publicly insured ethnic minorities. PMID- 24212161 TI - Health literacy and nutrition behaviors among low-income adults. AB - The purpose of this study was to explore the relationship between health literacy and nutrition behaviors using a low-income sample. Face-to-face surveys at 11 social services offices generated a convenience sample of 154 Supplemental Nutrition Assistance Program (SNAP)-eligible adults. We assessed health literacy, fruit and vegetable intake, food label use, consumption of healthy foods, and demographic characteristics. Thirty seven percent of the sample had adequate health literacy as measured by the Newest Vital Sign (NVS). Race and parenthood were significantly related to health literacy scores. Adequate health literacy, as measured by the NVS, was associated with frying chicken less often and eating the peels of fresh fruit more often. The findings suggest that health practitioners should ensure nutrition-related messages are accessible to all of their clients, especially those with the lowest health literacy levels. PMID- 24212162 TI - Leaving before discharge from a homeless Medical Respite program: predisposing factors and impact on selected outcomes. AB - BACKGROUND: Medical Respite addresses care needs of homeless patients post hospital discharge and is linked to reduced rehospitalization compared with standard discharge. However, outcomes may differ for Respite patients who exit before completing post-acute treatment and discharge plans. METHODS: Using administrative data from a San Francisco Medical Respite center (2007-2010), this retrospective study compares patient characteristics, post-Respite connections to community services, and likelihood of rehospitalization within 90 days of Respite exit between patients who choose to leave before discharge and all other Respite patients (logistic regression, odds ratio). FINDINGS: Of 860 encounters, 31% ended when patient chose to leave before discharge. Female gender (OR 1.65), living on the street immediately prior to Respite (OR 1.36) and substance use (OR 1.55) were associated with increased risk of leaving early. Patients who left early were more likely than others to decline referrals to services and more likely to be re-admitted within 90 days. PMID- 24212163 TI - Pandemics and vaccines: perceptions, reactions, and lessons learned from hard-to reach Latinos and the H1N1 campaign. AB - This paper examines knowledge, risk perception, and attitudes around the H1N1 pandemic among Latino hard-to-reach (HTR) populations in the United States. Ten focus groups were conducted throughout California (N=90), representing Latino immigrants disproportionately affected by H1N1: farmworkers, indigenous Mexicans, pregnant women, and children. Overall, participants were aware of the H1N1 epidemic and common prevention practices. However, many expressed doubts that the H1N1 outbreak constituted an epidemic because the U.S. media reports of the epidemic in Mexico did not match reports from participants' families in Mexico and because of participants' absence of personal experience with the disease. Participants mistrusted the H1N1 vaccine due to its novelty, conspiracy theories, and inconsistent information. Study findings confirm that vaccination campaign strategies should reflect the diversity of meaning, experiences, and socio economic realities among target populations. Key findings inform future emergency response activities targeting HTR Latino communities. PMID- 24212164 TI - Construct validity of the SF-12 among American Indian and Alaska Native people using two known scoring methods. AB - OBJECTIVE: This study evaluated the construct validity of the 12-Item Short Form Survey Instrument (SF-12) in a cohort of American Indian and Alaska Native (AIAN) people. We evaluated two scoring methods to determine their utility in this population. METHODS: Participants (N = 11,127) were aged 18 and older, self identified as AIAN, and had complete SF-12 interview data. Physical and mental health summary scores were calculated using traditional SF-12 (PCS12 and MCS12) and RAND-12 (PHC and MHC) scoring methods. RESULTS: Women scored lower than men on the PHC, PCS12, MHC, and MCS12, as did those with more medical conditions versus none. Those aged 55 and older scored lower on the PHC and PCS12 than younger people. There was no difference in the mean MCS12 score by age and for those 31-55 and aged older than 55 for the MHC. CONCLUSIONS: This study demonstrates the construct validity of the PCS12/MCS12 and PHC/MHC in a cohort of AIAN people. PMID- 24212165 TI - The effect of advance directives on end-of-life cost experience. AB - PURPOSE: This study assesses the impact of Advance Directives (ADs) on end-of life costs, drawing on administrative data from a single health care organization located in Milwaukee, Wisconsin (Independent Care Health Plan, or iCare). BACKGROUND: As part of ongoing Medicaid and Medicare rate reform efforts, greater use of ADs among plans and providers is being considered to better control costs and enhance health outcomes. APPROACH: Drawing on decedent-member descriptive and cost data, OLS regression is used to analyze the relationship between AD use and subsequent costs for a single health care plan. RESULTS: The analysis does not provide evidence of a significant relationship between AD use and end-of-life costs when patient health is controlled for the sample. CONCLUSIONS: There was no evidence within the iCare data to support a relationship between the presence of ADs and lower end-of-life costs. PMID- 24212166 TI - Prevalence of fracture and osteoporosis risk factors in American Indian and Alaska Native people. AB - OBJECTIVE: Little is known about prevalence of osteoporosis risk factors among American Indians and Alaska Natives (AIAN). METHODS: We included AIAN people (n=8,039) enrolled in the Education and Research Towards Health (EARTH) Study. Prevalence ratios were used to determine cross-sectional associations of risk factors with self-reported bone fractures. RESULTS: There is a high prevalence of multiple risk factors for osteoporosis in AIAN, although the factors that are associated with past fracture vary by gender and geographical area. In general, women who reported a fracture reported more risk behaviors, more than two medical conditions, and low physical activity. Men with higher BMI were less likely to report a fracture. Smoking history was associated with fracture for both genders, though not significantly in all sub-groups. CONCLUSION: We prevent a high prevalence of risk factors for osteoporosis for AIAN. Future research for osteoporosis risk reduction and prevention in AIAN people is indicated. PMID- 24212167 TI - Chronic health conditions and depressive symptoms strongly predict persistent food insecurity among rural low-income families. AB - Longitudinal studies of food insecurity have not considered the unique circumstances of rural families. This study identified factors predictive of discontinuous and persistent food insecurity over three years among low-income families with children in rural counties in 13 U.S. states. Respondents reported substantial knowledge of community resources, food and finance skills, and use of formal public food assistance, yet 24% had persistent food insecurity, and another 41% were food insecure for one or two years. Multivariate multinomial regression models tested relationships between human capital, social support, financial resources, expenses, and food insecurity. Enduring chronic health conditions increased the risk of both discontinuous and persistent food insecurity. Lasting risk for depression predicted only persistent food insecurity. Education beyond high school was the only factor found protective against persistent food insecurity. Access to quality physical and mental health care services are essential to ameliorate persistent food insecurity among rural, low-income families. PMID- 24212168 TI - Do free clinics reduce unnecessary emergency department visits? The Virginian experience. AB - As part of the safety net, free clinics (FCs) increase access to preventive and primary care for the uninsured. This study compared a group of uninsured FC users and a group of uninsured non-FC users to explore the impact of FC enrollment on the pattern of ED visits, as characterized by (1) level of complexity of care received at the ED, and (2) avoidable vs. unavoidable as classified by an existing clinical algorithm. Emergency department visits by FC users were less likely to be low-level-of-care than visits by non-FC users (OR 0.89, 95% CI 0.84 0.93). Free clinic enrollment was not a statistically significant predictor of avoidable visits (p=.6465). We found that the group of individuals who had access to primary care at the local FCs were significantly less likely than the group of uninsured individuals who were not enrolled in a FC to use the ED for care with lower levels of clinical complexity. Thus, the cost of increasing the primary care workforce as the Medicaid population expands may be worth it in the long run. Further exploration into what characterizes an effective FC is needed. PMID- 24212169 TI - Oral health activities of Early Head Start and Migrant and Seasonal Head Start programs. AB - Guidelines recommend that Migrant and Seasonal Head Start programs (MSHS) address the dental needs of children of migrant and seasonal farmworkers. This study describes parent- and child-oriented oral health activities of North Carolina's MSHS programs and compares them with non-migrant Early Head Start (EHS) programs using data collected from a questionnaire completed by teachers and family services staff. Migrant and Seasonal Head Start staff reported engaging in more oral health activities than EHS staff, which was confirmed by results of logit and ordered logit regression models. Despite promising findings about the engagement of MSHS staff, participation in oral health activities is lower than recommended. Differences between EHS and MSHS programs might be due to differing needs of enrolled children and families or to different approaches to meeting the needs of families. PMID- 24212170 TI - Predictors of smoking cessation counseling adherence in a socioeconomically disadvantaged sample of pregnant women. AB - Implementing and evaluating smoking cessation interventions in underserved populations has been found difficult due to high rates of non-adherence to the prescribed protocol. To understand better the barriers to cessation participation, we studied low-income inner-city pregnant women who were enrolled in either a standard or highly intensive quit smoking counseling program. The results showed that 1) in the prenatal phase, non-attendance was predicted by a greater number of cigarettes smoked per day; 2) in the postpartum follow-up phase, non-attendance was predicted by lower educational level and higher self efficacy for quitting smoking; and 3) participants with more children living at home were at increased risk of rescheduling the postpartum follow-up session. These findings suggest that innovative delivery strategies are needed more effectively to assess and address risk factors for non-adherence to smoking cessation trials among underserved minority pregnant/postpartum smokers. PMID- 24212171 TI - Drug resistance strategies of rural Hawaiian youth as a function of drug offerers and substances: a community stakeholder analysis. AB - This study examined the variations in drug resistance strategies endorsed by community members for rural Native Hawaiian youth in drug-related problem situations. Community stakeholders completed a Web-based survey focused on drug related problem scenarios and their matched set of responses developed by middle/intermediate school youth in prior research. Mean differences were examined based on drug offerers described in the scenarios (i.e., peers/friends, cousins, and parents) and the substances offered in the scenarios (i.e., marijuana and alcohol). Compared with other strategies, Refuse had the highest mean scores within two offerer subgroups (peers/friends and cousins) and within both substances (alcohol and marijuana). Leave had the highest mean score within scenarios describing drug offers from parents. The endorsement of different resistance strategies varied based on drug offerers and substances offered in the selected scenarios. This study suggests that resistance skills in prevention should be tailored to youths' social context in rural Hawai'i. PMID- 24212172 TI - Faith leaders' comfort implementing an HIV prevention curriculum in a faith setting. AB - YOUR Blessed Health (YBH) is a faith-based HIV prevention pilot program designed to increase faith-based organizations' capacity to address HIV/AIDS among African American congregations. Faith leaders (e.g., pastors, pastors' spouses) were trained to deliver youth and adult HIV education sessions. Perceptions of comfort with discussing 11 sexual health topics were assessed after program implementation. Twenty-nine faith leaders self-reported their comfort discussing sexual behaviors, sexual communication, and sexual abuse. Overall, faith leaders were comfortable discussing these sexual health topics; however, denominational and leadership role differences were found. These findings suggest African American faith leaders are willing to lead faith-based HIV prevention efforts, but that consideration of denominational differences and organizational roles in faith-based health promotion programs is critical. PMID- 24212173 TI - Addressing poverty and HIV using microenterprise: findings from qualitative research to reduce risk among unemployed or underemployed African American women. AB - INTRODUCTION: Microenterprise programs are widely used to improve health outcomes among women internationally. However, there is little information on applicability to American women living in poverty. We conducted formative research to identify activities that are viable and attractive, that may produce income to address some proportion of economic need and could be incorporated in the development of a micro-enterprise HIV-prevention intervention to reduce HIV/STD transmission among unemployed or underemployed African American women at risk for HIV. METHODS: Focus groups were convened with young African American women and community leaders in two southern states. Interviews with women participating in the focus groups were also convened. RESULTS: Findings suggest an intervention should incorporate activities to increase self-esteem, enhance employability and job sustainability to decrease financial dependence. This research serves as the foundation for developing a novel approach to HIV prevention in the U.S. that may directly address poverty as a social determinant of health. PMID- 24212174 TI - Diagnostic resolution of cancer screening abnormalities at community health centers. AB - BACKGROUND: Few studies have examined timeliness of diagnostic evaluation of abnormal cancer screening tests in community health centers. METHODS: Using medical record review, timeliness of diagnosis was assessed among 317 people having either breast or colorectal-related abnormalities. RESULTS: For 241 subjects (76.0%) who reached clinical resolution, the median time to diagnostic resolution was 37 days. People with breast abnormalities had more than twice the odds (adjusted odds ratio: 2.84) of reaching diagnostic resolution within 180 days compared with patients with colorectal abnormalities. We found, however, no evidence of disparate outcomes according to patient race/ethnicity, insurance status, or spoken language. CONCLUSIONS: Diagnostic evaluations are often either not completed or are delayed after a cancer-related abnormality is discovered. Further research is needed to understand the patient, provider, and health care system factors that contribute to these delays. There was no evidence of cancer disparities in the community health centers studied. PMID- 24212175 TI - Types of dental fear as barriers to dental care among African American adults with oral health symptoms in Harlem. AB - To examine the types of dental fear experienced by African American adults and the role of these fears in the utilization of dental care, in-depth interviews were conducted with a street-intercept sample of 118 African Americans living in Harlem, New York City, who had experienced at least one oral health symptom in the past six months. Despite their oral symptoms, participants delayed or avoided dental care (often for years) due to a variety of dental fears, including fears of: 1) pain from needles; 2) the dental drill; 3) having teeth extracted; 4) contracting an illness (e.g., HIV/AIDS) from unsanitary instruments; 5) X-rays; 6) receiving poor quality care or mistreatment. These findings provide insights into the situations that provoke fears about dental treatment among African Americans and suggest strategies to address these fears in order to remove these barriers and increase the utilization of dental care by African American adults. PMID- 24212176 TI - Reported experiences during syringe purchases in Providence, Rhode Island: implications for HIV prevention. AB - Use of injection drugs remains a public health concern, with injection drug users (IDUs) experiencing an elevated risk of morbidity and mortality. While the sale of non-prescription syringes in pharmacies is legal in most states, some pharmacists choose not to sell non-prescription syringes, or opt to sell syringes in quantities too large for purchase by many IDUs. Thus, we sought to understand the interpersonal experience of syringe sale/ purchase, the implications of policies regarding syringe sales, and pharmacy staff and IDU (mis)perceptions about one another. We conducted in-depth, semi-structured interviews with 21 IDUs and 21 pharmacy staff (pharmacists and pharmacy technicians). Some important emergent themes were that individual experiences influenced overall perceptions, that IDUs and pharmacy staff differentiated between IDUs and other customers, and that some pharmacy staff demonstrated an understanding of the public health importance of accessible sterile syringes. Implications for future pharmacy-based interventions for IDUs are considered. PMID- 24212177 TI - Health care access and use among the rural uninsured. AB - The uninsured have poorer access to care and obtain care at greater acuity than those with health insurance; however, the differential impact of being uninsured in rural versus urban areas is largely unknown. Using data from the 2002-2007 Medical Expenditure Panel Survey, we examine whether uninsured rural residents have different patterns of health care use than their urban counterparts, and the factors associated with any differences. We find that being uninsured leads to poorer access in both rural and urban areas, yet the rural uninsured are more likely to have a usual source of care and use services than their urban counterparts. Further, controlling for demographic and health characteristics, the access and use differences between the uninsured and insured in rural areas are smaller than those observed in urban areas. This suggests that rural providers may impose fewer barriers on the uninsured who seek care than providers in urban areas. PMID- 24212179 TI - A note from the editor. PMID- 24212180 TI - Influence of open vegetation fires on black carbon and ozone variability in the southern Himalayas (NCO-P, 5079 m a.s.l.). AB - We analysed the variability of equivalent black carbon (BC) and ozone (O3) at the global WMO/GAW station Nepal Climate Observatory-Pyramid (NCO-P, 5079 m a.s.l.) in the southern Himalayas, for evaluating the possible contribution of open vegetation fires to the variability of these short-lived climate forcers/pollutants (SLCF/SLCP) in the Himalayan region. We found that 162 days (9% of the data-set) were characterised by acute pollution events with enhanced BC and O3 in respect to the climatological values. By using satellite observations (MODIS fire products and the USGS Land Use Cover Characterization) and air mass back-trajectories, we deduced that 56% of these events were likely to be affected by emissions from open fires along the Himalayas foothills, the Indian Subcontinent and the Northern Indo-Gangetic Plain. These results suggest that open fire emissions are likely to play an important role in modulating seasonal and inter-annual BC and O3 variability over south Himalayas. PMID- 24212183 TI - Microbial analyses of contact lens-associated microbial keratitis. AB - PURPOSE: To investigate the utility of additional microbial analyses to detect the causative microorganism of microbial keratitis and to determine the strength of association between clinical variables. METHODS: This retrospective study included 125 eyes of 123 people presenting with presumed infectious keratitis associated with contact lens wear, and examined between January 2001 and November 2011. RESULTS: Sixty-three male and 60 female patients with a mean age of 24.14 ( +/-6.7) and 26.7 (+/-10.0) years, respectively, were included in the study. Among the samples tested, 38 (40%) corneal cultures, 85 (92%) contact lens cultures, and 49 (80%) contact lens case cultures yielded positive results. In the samples for which all microbial investigations were performed and corneal culture was positive, cultures of contact lenses and corneas yielded the same microbes in 94% of cases, and for contact lens case and corneal cultures 77% of cases yielded the same microbes. Importantly, these were monocultures of the same microbe isolated from the cornea in the contact lens and lens case cultures. The odds of having a positive corneal culture was 37 times higher (p = 0.008) when patients presented to the clinic 2 weeks after the onset of symptoms. Pseudomonas aeruginosa was the predominant organism isolated, and most isolates were susceptible to commonly used antimicrobials. CONCLUSIONS: Contact lens culture might be an effective test to perform to detect and determine the causative microorganism when corneal cultures are unavailable or yield no microorganisms upon culture. A longer duration of symptoms before presenting to the clinic was significantly associated with obtaining a positive corneal culture. PMID- 24212181 TI - Antibacterial and antidiarrheal activities of plant products against enterotoxinogenic Escherichia coli. AB - Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This treatment is often not available to people in developing countries, and several die from the condition provoke by ETEC. Over the years, plants and plant extracts have been use as traditional medicine to treat various gastrointestinal ailments including diarrhea. Many of these plant products have been claimed to be active against diarrhea, however few have been extensively studied. The main objective of this review was to gather the scattered information on the antidiarrheal activities reported for various plant products on ETEC. This includes two major effects: (1) The inhibitory effect on bacterial growth or viability and (2) The interference with ETEC enterotoxins activity upon the intestinal epithelium. We will focus on plant products and extracts for which we have major indications of their biological activity against ETEC and their enterotoxins. Because Vibrio cholerae toxin (CT) is structurally, antigenically and mechanistically related to LT, it will also be discussed in this review. PMID- 24212182 TI - From the gastrointestinal tract (GIT) to the kidneys: live bacterial cultures (probiotics) mediating reductions of uremic toxin levels via free radical signaling. AB - A host of compounds are retained in the body of uremic patients, as a consequence of progressive renal failure. Hundreds of compounds have been reported to be retention solutes and many have been proven to have adverse biological activity, and recognized as uremic toxins. The major mechanistic overview considered to contribute to uremic toxin overload implicates glucotoxicity, lipotoxicity, hexosamine, increased polyol pathway activity and the accumulation of advanced glycation end-products (AGEs). Until recently, the gastrointestinal tract (GIT) and its associated micro-biometabolome was a neglected factor in chronic disease development. A systematic underestimation has been to undervalue the contribution of GIT dysbiosis (a gut barrier-associated abnormality) whereby low-level pro inflammatory processes contribute to chronic kidney disease (CKD) development. Gut dysbiosis provides a plausible clue to the origin of systemic uremic toxin loads encountered in clinical practice and may explain the increasing occurrence of CKD. In this review, we further expand a hypothesis that posits that environmentally triggered and maintained microbiome perturbations drive GIT dysbiosis with resultant uremia. These subtle adaptation responses by the GIT microbiome can be significantly influenced by probiotics with specific metabolic properties, thereby reducing uremic toxins in the gut. The benefit translates to a useful clinical treatment approach for patients diagnosed with CKD. Furthermore, the role of reactive oxygen species (ROS) in different anatomical locales is highlighted as a positive process. Production of ROS in the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which acts as an essential second messenger required for normal cellular homeostasis and physiological function. Whilst this critical review has focused on end-stage CKD (type 5), our aim was to build a plausible hypothesis for the administration of probiotics with or without prebiotics for the early treatment of kidney disease. We postulate that targeting healthy ROS production in the gut with probiotics may be more beneficial than any systemic antioxidant therapy (that is proposed to nullify ROS) for the prevention of kidney disease progression. The study and understanding of health-promoting probiotic bacteria is in its infancy; it is complex and intellectually and experimentally challenging. PMID- 24212184 TI - Reading training with threshold stimuli in people with central vision loss: a feasibility study. AB - PURPOSE: To evaluate the effectiveness of a perceptual learning technique for improving reading performance of patients with central vision loss and to explore whether this learning generalizes to other visual functions. METHODS: Ten patients with central vision loss were trained binocularly, in four consecutive sessions, with serially presented words printed at each patient's reading acuity limit. Patients read 10 blocks of 100 words in each session. They were encouraged to read the whole word and were discouraged to read letter by letter. Assessment sessions before and after training measured fixation stability, monocular and binocular visual acuity, as well as reading acuity, critical print size, and maximum reading speed with continuous text. Another six patients with central vision loss were included in a test-retest control group and were tested twice, 1 week apart, with no intervention. RESULTS: The average time required to read a block of trials decreased significantly with each training session. After training, continuous text reading improved in terms of reading acuity (p = 0.017) and maximum reading speed (p = 0.01), but critical print size did not change. Binocular acuity improved significantly from an average of 0.54 logMAR before training to 0.44 logMAR after training. Binocular ratio (better eye acuity/binocular acuity) increased from an average of 1.0 before training to 1.17 after training. There was a 62% improvement in fixation stability in the better eye and 58% in the worse eye. There were no changes in the outcome measures for the test-retest control group. CONCLUSIONS: The technique described in this article can be used for vision rehabilitation of patients with central vision loss. When training is done with size threshold stimuli, learning generalizes to visual acuity, continuous text reading, and fixation stability. PMID- 24212185 TI - An evidence-based analysis of Australian optometrists' dry eye practices. AB - PURPOSE: The aims of this study were to investigate the clinical practices of Australian optometrists as related to the diagnosis, quantification, and management of dry eye and to assess whether these are consistent with research evidence and current guidelines. METHODS: An online survey was distributed to registered optometrists (n = 654). Respondents provided information regarding their preferred diagnostic procedures and management strategies for dry eye, practice modality, year of commencing practice, and whether they possessed an interest in dry eye. RESULTS: Respondents (n = 144) used multiple procedures for diagnosis. Recording patient symptoms ranked as the most important, most valuable, and most commonly used technique. The main objective tests were fluorescein-assisted tear breakup time, corneal fluorescein staining, and meibomian gland evaluation. Optometrists with an interest in dry eye more frequently used lissamine green, phenol red test, interference fringes, and tear osmolarity than nonspecialist practitioners. Dry eye treatment varied with severity. The mainstay of therapy was nonpreserved lubricants and eyelid hygiene; more practitioners recommended topical corticosteroids, systemic omega-3 fatty acid supplementation and increased dietary intake of omega-3 fatty acids for moderate and severe disease, respectively. The primary sources of information used to guide practitioners' management were derived from continuing education conferences. CONCLUSIONS: This study indicates that although Australian optometrists use subjective and objective diagnostic tests and stratify treatment based on dry eye severity, there is a lack of uniformity regarding diagnostic testing, infrequent use of standardized grading scales, and significant variability in clinical care. These findings highlight the potential to improve the translation of dry eye research evidence and evidence-based guidelines into Australian optometric practice. PMID- 24212186 TI - Evaluation of age-related changes in noninvasive tear breakup time. AB - PURPOSE: To establish normal noninvasive tear film breakup time (NI-BUT) values in the Chinese population and investigate age-related changes in NI-BUT using a newly developed Keratograph. METHODS: Forty normal volunteers with a mean age of 32.8 +/- 16.7 years were recruited for this study. Clinical and demographic data, including age, gender, fluorescein tear film breakup time (FBUT), and Schirmer I test values were collected from the subjects. Noninvasive tear film breakup time was measured using a new method based on a corneal topographer equipped with a modified scan software. The correlations between the NI-BUT, age, and gender were determined. RESULTS: In total, a significant difference between the NI-BUT and the FBUT was found (4.9 +/- 2.4 seconds vs. 9.0 +/- 3.0 seconds; p < 0.001). No statistically significant difference in the NI-BUT was observed between the male and female subjects (5.5 +/- 2.0 seconds vs. 4.5 +/- 2.5 seconds; p = 0.137). In addition, no significant correlation was detected between the NI-BUT and age (0.143, p = 0.321). CONCLUSIONS: The NI-BUT values found in this study are much lower than those of previous reports. Our results show no significant differences in tear film stability with age. The tear physiology of the Chinese population may not be the same as in Western populations. PMID- 24212187 TI - Treatment outcomes of myopic anisometropia with 1% atropine: a pilot study. AB - PURPOSE: To investigate the safety and efficacy of the treatment of myopic anisometropia with 1% atropine. METHODS: Twenty-two children with myopic anisometropia were prescribed 1% solution of atropine sulfate to the more myopic eye, one drop before sleep every 3 days. Children were visited every 3 to 4 months until the degree of anisometropia was no more than 0.5 diopters (D) ("Success") or unchanged after 9 months of treatment ("No effect"). The treatment effect was assessed by comparing the interocular imbalance in refraction and axial length before and after the treatment. A detailed questionnaire about subjective symptoms in each visit and an electroretinogram in the end were administered to evaluate the side effects of this treatment. RESULTS: The subjects were followed for 7 to 16 months. Six subjects withdrew participation on their own accord, and three were excluded because of inconstant usage of drug. Of the 13 remaining subjects, the refraction of the treated eyes decreased by 0.63 +/- 0.59 D (p = 0.007), whereas that of the untreated eyes increased by -0.72 +/- 0.65 D (p < 0.001). A corresponding trend was also found in the change of the axial length. Accordingly, the level of anisometropia was reduced from 1.82 +/- 0.73 D to 0.47 +/- 0.65 D (p < 0.001) and 10 (76.9%) of the 13 subjects were designated a "Success." One percent atropine was well tolerated by the children, and no electroretinogram abnormality was detected. CONCLUSIONS: The results from this pilot study indicate that monocular usage of a solution of 1% atropine sulfate is an effective treatment to reduce anisometropia, although with some tolerable side effects. Nevertheless, an attenuated benefit was observed after cessation of atropine treatment. Thus, participants should be informed of a possible rebound effect before the administration of atropine for myopic anisometropia. PMID- 24212188 TI - Age-related changes in corneal pulsation: ocular dicrotism. AB - PURPOSE: To evaluate age-related changes in the shape of corneal indentation pulse (CIP) in relation to simultaneously registered blood pulsation (BPL) and electrocardiogram (ECG) signals in healthy subjects. METHODS: Seventy-seven subjects were recruited for the study, including 36 young subjects (aged 23 to 32 years) and 41 older subjects (aged 44 to 72 years) with no reported ocular and cardiovascular abnormalities and free of any systemic diseases. Corneal indentation pulse was measured with a noninvasive ultrasonic distance sensor. Simultaneously, BPL and ECG were acquired with a pulse oximeter placed on the earlobe and Eindhoven triangle setup, respectively. Correlation analysis was applied to identify the interactions between the parameters of the averaged signals, estimated with dedicated signal processing algorithms, for all subject measurements and separately for both considered groups. RESULTS: Twenty-nine out of 41 older subjects showed evidence of a double peak-shaped CIP waveform that could be interpreted as ocular pulse dicrotism. None of the young subjects exhibited this phenomenon. For the young group, significant correlations (p < 0.05) were found between the CIP crest time of a single peak-shaped CIP waveform and the other shape parameters of the CIP, BPL, and ECG signals. Similarly, for the older group of subjects, significant corresponding correlations were only found between the preliminary crest time of a double peak-shaped CIP waveform. CONCLUSIONS: Using noninvasive corneal indentation pulse measurement revealed, for the first time, an ocular pulse dicrotism. This might be a natural sign of aging or an early indication of hemodynamic aspects of cardiovascular diseases. PMID- 24212189 TI - Corneal confocal microscopy for vision disturbance after an epithelial abrasion. AB - PURPOSE: To demonstrate the use of in vivo corneal confocal microscopy to reveal the reason for persistent disturbance of vision after a corneal abrasion. CASE REPORT: A 49-year-old man presented with a decrease in visual acuity and monocular diplopia after a traumatic corneal abrasion. Anterior segment optical coherence tomography was not beneficial. In vivo corneal confocal microscopy showed abnormal folding in the basal epithelial layer of the cornea. Based on these findings, a therapeutic abrasion of the affected epithelium was performed. Visual acuity returned to 1.0 after therapeutic abrasion, and overall findings on the eye were within physiological limits. Control corneal confocal microscopic examination confirmed reparation of the structure of epithelial cell layers. CONCLUSIONS: The in vivo corneal confocal microscopy can reveal corneal pathologic abnormality even in cases where other methods are not beneficial. Alongside other modern methods, it may become an important tool to help locate pathologic abnormality accurately and choose the proper therapeutic strategy. PMID- 24212190 TI - Training students with patient actors improves communication: a pilot study. AB - PURPOSE: Effective patient communication is correlated with better health outcomes and patient satisfaction, but is challenging to train, particularly with difficult clinical scenarios such as loss of sight. In this pilot study, we evaluated the use of simulated patient encounters with actors to train optometric students. METHODS: Students were recorded during encounters with actors and assigned to an enrichment group performing five interactions with instructor feedback (n = 6) or a no-enrichment group performing two interactions without feedback (n = 4). Student performance on first and last encounters was scored with (1) subjective rating of performance change using a visual analog scale (anchors: much worse/much better), (2) yes/no response: Would you recommend this doctor to a friend/relative?, and (3) average score on questions from the American Board of Internal Medicine (ABIM) assessment of doctor communication skills. Three clinical instructors, masked to student group assignments and the order of patient encounters they viewed, provided scores in addition to self evaluation by students and patient-actors. RESULTS: Using the visual analog scale, students who received enrichment were rated more improved than the no enrichment group by masked examiners (+18 vs. -11% p = 0.04) and self-evaluation (+79 vs. +27% p = 0.009), but not by actors (+31 vs. +43%). The proportion of students recommended significantly increased following enrichment for masked examiners (61% vs. 94%; p < 0.001), but not actors (100 vs. 83%). Average ABIM assessment scores were not significantly different by any rating group: masked instructors, actors, or self-ratings. CONCLUSIONS: The findings of this study suggest five simulated patient encounters with feedback result in measurable improvement in student-patient communication skills as rated by masked examiners. PMID- 24212191 TI - Cross-coupling reaction between arylboronic acids and carboranyl iodides catalyzed by graphene oxide (GO)-supported Pd(0) recyclable nanoparticles for the synthesis of carboranylaryl ketones. AB - Well-dispersed palladium(0) nanoparticles with small and narrow size distributions were synthesized conveniently on a graphene oxide (GO) surface. The GO-supported nano-Pd(0) was found to be a highly efficient and recyclable catalyst for the carbonylative cross-coupling reaction between arylboronic acids and aryl and carboranyl iodides, respectively. Benzophenone and a series of carboranylaryl ketones, 1-R-2-[C(=O)Ar]-1,2-C2B10H10 (R = H, Me, Ph; Ar = C6H5, C6H4-4-OMe and C6H4-4-F), were synthesized and fully characterized. The catalyst was recyclable at least three times with sustained activity. PMID- 24212194 TI - C-H nitrogenation and oxygenation by ruthenium catalysis. AB - Remarkable recent progress has been accomplished in direct C-H functionalizations for the formation of C-N and C-O bonds through the use of readily accessible ruthenium catalysts. Particularly, ruthenium(II) complexes allowed for challenging direct C(sp(2))-H hydroxylation of arenes. These catalysts set the stage for step-economical C-H functionalization with electron-rich as well as electron-deficient (hetero)arenes and, therefore, provided versatile access to diversely decorated phenols. While a number of synthetically useful protocols for ruthenium-catalyzed C(sp(3))-H bond nitrogenation have been elaborated, the analogous transformations of more stable C(sp(2))-H bonds were very recently achieved. PMID- 24212193 TI - Analyses of interactions between heparin and the apical surface proteins of Plasmodium falciparum. AB - Heparin, a sulfated glycoconjugate, reportedly inhibits the blood-stage growth of the malaria parasite Plasmodium falciparum. Elucidation of the inhibitory mechanism is valuable for developing novel invasion-blocking treatments based on heparin. Merozoite surface protein 1 has been reported as a candidate target of heparin; however, to better understand the molecular mechanisms involved, we characterized the molecules that bind to heparin during merozoite invasion. Here, we show that heparin binds only at the apical tip of the merozoite surface and that multiple heparin-binding proteins localize preferentially in the apical organelles. To identify heparin-binding proteins, parasite proteins were fractionated by means of heparin affinity chromatography and subjected to immunoblot analysis with ligand-specific antibodies. All tested members of the Duffy and reticulocyte binding-like families bound to heparin with diverse affinities. These findings suggest that heparin masks the apical surface of merozoites and blocks interaction with the erythrocyte membrane after initial attachment. PMID- 24212195 TI - Cognitive processes in anesthesiology decision making. AB - The quality and safety of health care are under increasing scrutiny. Recent studies suggest that medical errors, practice variability, and guideline noncompliance are common, and that cognitive error contributes significantly to delayed or incorrect diagnoses. These observations have increased interest in understanding decision-making psychology.Many nonrational (i.e., not purely based in statistics) cognitive factors influence medical decisions and may lead to error. The most well-studied include heuristics, preferences for certainty, overconfidence, affective (emotional) influences, memory distortions, bias, and social forces such as fairness or blame.Although the extent to which such cognitive processes play a role in anesthesia practice is unknown, anesthesia care frequently requires rapid, complex decisions that are most susceptible to decision errors. This review will examine current theories of human decision behavior, identify effects of nonrational cognitive processes on decision making, describe characteristic anesthesia decisions in this context, and suggest strategies to improve decision making. PMID- 24212196 TI - Addressing the mandate for hand-off education: a focused review and recommendations for anesthesia resident curriculum development and evaluation. AB - The Accreditation Council for Graduate Medical Education requires that residency programs teach residents about handoffs and ensure their competence in this communication skill. Development of hand-off curricula for anesthesia residency programs is hindered by the paucity of evidence regarding how to conduct, teach, and evaluate handoffs in the various settings where anesthesia practitioners work. This narrative review draws from literature in anesthesia and other disciplines to provide recommendations for anesthesia resident hand-off curriculum development and evaluation. PMID- 24212197 TI - Designing and implementing the objective structured clinical examination in anesthesiology. AB - Since its description in 1974, the Objective Structured Clinical Examination (OSCE) has gained popularity as an objective assessment tool of medical students, residents, and trainees. With the development of the anesthesiology residents' milestones and the preparation for the Next Accreditation System, there is an increased interest in OSCE as an evaluation tool of the six core competencies and the corresponding milestones proposed by the Accreditation Council for Graduate Medical Education.In this article the authors review the history of OSCE and its current application in medical education and in different medical and surgical specialties. They also review the use of OSCE by anesthesiology programs and certification boards in the United States and internationally. In addition, they discuss the psychometrics of test design and implementation with emphasis on reliability and validity measures as they relate to OSCE. PMID- 24212199 TI - Can simulation help to answer the demand for echocardiography education? AB - There has been a recent explosion of education and training in echocardiography in the specialties of anesthesiology and critical care. These devices, by their impact on clinical management, are changing the way surgery is performed and critical care is delivered. A number of international bodies have made recommendations for training and developed examinations and accreditations.The challenge to medical educators in this area is to deliver the training needed to achieve competence into already over-stretched curricula.The authors found an apparent increase in the use of simulators, with proven efficacy in improving technical skills and knowledge. There is still an absence of evidence on how it should be included in training programs and in the accreditation of certain levels.There is a conviction that this form of simulation can enhance and accelerate the understanding and practice of echocardiography by the anesthesiologist and intensivists, particularly at the beginning of the learning curve. PMID- 24212198 TI - Facilitation of resident scholarly activity: strategy and outcome analyses using historical resident cohorts and a rank-to-match population. AB - BACKGROUND: Facilitation of residents' scholarly activities is indispensable to the future of medical specialties. Research education initiatives and their outcomes, however, have rarely been reported. METHODS: Since academic year 2006, research education initiatives, including research lectures, research problem based learning discussions, and an elective research rotation under a new research director's supervision, have been used. The effectiveness of the initiatives was evaluated by comparing the number of residents and faculty mentors involved in residents' research activity (Preinitiative [2003-2006] vs. Postinitiative [2007-2011]). The residents' current postgraduation practices were also compared. To minimize potential historical confounding factors, peer reviewed publications based on work performed during residency, which were written by residents who graduated from the program in academic year 2009 to academic year 2011, were further compared with those of rank-to-match residents, who were on the residency ranking list during the same academic years, and could have been matched with the program of the authors had the residents ranked it high enough on their list. RESULTS: The Postinitiative group showed greater resident research involvement compared with the Preinitiative group (89.2% [58 in 65 residents] vs. 64.8% [35 in 54]; P = 0.0013) and greater faculty involvement (23.9% [161 in 673 faculty per year] vs. 9.2% [55 in 595]; P < 0.0001). Choice of academic practice did not increase (50.8% [Post] vs. 40.7% [Pre]; P = 0.36). Graduated residents (n = 38) published more often than the rank-to-match residents (n = 220) (55.3% [21 residents] vs. 13.2% [29]; P < 0.0001, odds ratio 8.1 with 95% CI of 3.9 to 17.2). CONCLUSION: Research education initiatives increased residents' research involvement. PMID- 24212201 TI - Low-frequency noise in multilayer MoS2 field-effect transistors: the effect of high-k passivation. AB - Diagnosing of the interface quality and the interactions between insulators and semiconductors is significant to achieve the high performance of nanodevices. Herein, low-frequency noise (LFN) in mechanically exfoliated multilayer molybdenum disulfide (MoS2) (~11.3 nm-thick) field-effect transistors with back gate control was characterized with and without an Al2O3 high-k passivation layer. The carrier number fluctuation (CNF) model associated with trapping/detrapping the charge carriers at the interface nicely described the noise behavior in the strong accumulation regime both with and without the Al2O3 passivation layer. The interface trap density at the MoS2-SiO2 interface was extracted from the LFN analysis, and estimated to be Nit ~ 10(10) eV(-1) cm(-2) without and with the passivation layer. This suggested that the accumulation channel induced by the back-gate was not significantly influenced by the passivation layer. The Hooge mobility fluctuation (HMF) model implying the bulk conduction was found to describe the drain current fluctuations in the subthreshold regime, which is rarely observed in other nanodevices, attributed to those extremely thin channel sizes. In the case of the thick-MoS2 (~40 nm-thick) without the passivation, the HMF model was clearly observed all over the operation regime, ensuring the existence of the bulk conduction in multilayer MoS2. With the Al2O3 passivation layer, the change in the noise behavior was explained from the point of formation of the additional top channel in the MoS2 because of the fixed charges in the Al2O3. The interface trap density from the additional CNF model was Nit = 1.8 * 10(12) eV(-1) cm(-2) at the MoS2-Al2O3 interface. PMID- 24212200 TI - Atomically precise edge chlorination of nanographenes and its application in graphene nanoribbons. AB - Chemical functionalization is one of the most powerful and widely used strategies to control the properties of nanomaterials, particularly in the field of graphene. However, the ill-defined structure of the present functionalized graphene inhibits atomically precise structural characterization and structure correlated property modulation. Here we present a general edge chlorination protocol for atomically precise functionalization of nanographenes at different scales from 1.2 to 3.4 nm and its application in graphene nanoribbons. The well defined edge chlorination is unambiguously confirmed by X-ray single-crystal analysis, which also discloses the characteristic non-planar molecular shape and detailed bond lengths of chlorinated nanographenes. Chlorinated nanographenes and graphene nanoribbons manifest enhanced solution processability associated with decreases in the optical band gap and frontier molecular orbital energy levels, exemplifying the structure-correlated property modulation by precise edge chlorination. PMID- 24212202 TI - How deaf American Sign Language/English bilingual children become proficient readers: an emic perspective. AB - A primary tenet underlying American Sign Language/English bilingual education for deaf students is that early access to a visual language, developed in conjunction with language planning principles, provides a foundation for literacy in English. The goal of this study is to obtain an emic perspective on bilingual deaf readers transitioning from learning to read to reading to learn. Analysis of 12 interactive, semi-structured interviews identified informal and formal teaching and learning practices in ASL/English bilingual homes and classrooms. These practices value, reinforce, and support the bidirectional acquisition of both languages and provide a strong foundation for literacy. PMID- 24212203 TI - Development and applications of remote stereocontrol using allylic organobismuth reagents. AB - Reactions of 5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane with aldehydes promoted by bismuth(III) iodide were usefully stereoselective in favour of the (E)-1,5-anti-6-benzyloxy-5-methylalk-3-en-1-ols. Similar stereoselectivity was observed for reactions of analogous 5-benzyloxy-4-methylpent-2-enyl bromides with aldehydes when promoted by a low valency bismuth species prepared by reduction of bismuth(III) triiodide with powdered zinc so providing a "tin-free" procedure. The analogous reactions of 4-benzyloxypent-2-enyl(tributyl)stannane with aldehydes promoted by bismuth(III) iodide were also stereoselective but gave lower yields. Attempted 1,6-stereocontrol using these reactions resulted in only modest stereoselectivities. Aspects of the chemistry of the products were studied in particular their stereoselective conversion into aliphatic compounds with methyl bearing stereogenic centres at 1,5,9,13- and 1,3,5-positions along the aliphatic chain. Mechanistically, allylic organobismuth species may be involved in both sets of reactions but this was not confirmed although the similar stereoselectivities observed for both the bismuth(III) iodide mediated reactions of the pent-2-enylstannanes and the low-valency bismuth promoted reactions of the pent-2-enyl bromides are consistent with participation of similar intermediates. PMID- 24212207 TI - Submacular hemorrhage: A study among Indian eyes. PMID- 24212204 TI - Assessment of peripapillary retinal nerve fiber layer thickness using scanning laser polarimetry (GDx VCC) in normal Indian children. AB - PURPOSE: To obtain reference values of RNFL thickness in normal Indian children and to study the association of RNFL thickness with central corneal thickness(CCT) and axial length(AL). MATERIALS AND METHODS: 200 normal Indian children (mean age 8.6 +/- 2.9 yrs) were examined on the GDxVCC. The inferior average (IA), superior average (SA), temporal-superior-nasal-inferior-temporal (TSNIT) average and nerve fiber index (NFI) values were recorded and compared between males and females as well as between the different age groups. The association of TSNIT average with AL and CCT was examined. RESULTS: Values for the RNFL parameters were-SA: 64.9 +/- 9.7, IA: 63.8 +/- 8.8, TSNIT average: 53.5 +/- 7.7 and NFI 21.5 +/- 10.8. Superior, inferior and TSNIT averages did not differ significantly between males and females (P = 0.25, P = 0.19, P = 0.06 respectively; Mann-Whitney U test). No significant differences were found in TSNIT average across age groups. There was a statistically significant positive correlation between CCT and TSNIT average (r = 0.25, r 2 = 0.06, P < 0.001). The correlation TSNIT average and AL(r = -0.12; r2 = 0.01) was not significant (P = 0.2). CONCLUSION: Reference values for RNFL parameters reported for Indian children are similar those reported in adults. There is a small correlation between central corneal thickness and RNFL as reflected in average TSNIT. PMID- 24212209 TI - Association between hyperacuity defects and retinal microstructure in polypoidal choroidal vasculopathy. AB - PURPOSE: To improve our understanding of hyperacuity defects measured with preferential hyperacuity perimetry (PHP) by correlating PHP findings with the retinal microstructural changes visible on spectral-domain optical coherence tomography (OCT) in patients with polypoidal choroidal vasculopathy (PCV). MATERIALS AND METHODS: Twenty-eight eyes of 28 patients with PCV were retrospectively reviewed. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (logMAR) testing, PHP, and OCT. The functional 'PHP test score' and 'total volume of hyperacuity defect zone' were also analyzed. RESULTS: Patients were classified based on the hyperacuity defect by PHP, as follows: Hyperacuity defect (n = 17 eyes) group and hyperacuity intact (n = 11 eyes) group. The mean best-corrected visual acuity in the hyperacuity intact group (0.46 +/- 0.39) was better than that in the hyperacuity defect group (0.82 +/- 0.37) (P = 0.014). The presence of serous retinal detachment and retinal pigment epithelial detachment did not differ significantly between groups (P = 0.120 and P = 0.689, respectively). A disrupted photoreceptor layer was more common in the hyperacuity defect group compared with the hyperacuity intact group (P = 0.0001). Among 17 eyes with a hyperacuity defect, 9 eyes showing intra-retinal pathology (intra-retinal cyst or hard exudates) and had a significantly higher PHP test score and larger total volume of the hyperacuity defect zone than 8 eyes without intra-retinal pathology (P = 0.006 and P = 0.021, respectively). CONCLUSION: A hyperacuity defect in PCV was associated with photoreceptor disarrangement. Furthermore, PCV lesions on the inner retina that invaded the photoreceptor layer were associated with a more severe hyperacuity defect. PMID- 24212210 TI - A case of subacute cutaneous lupus erythematosus as a result of ranibizumab (Lucentis) treatment. AB - Cutaneous lupus erythematosus is a previously undiagnosed side-effect of ranibizumab. Here, we present a case of an 82-year-old female Caucasian patient with wet age-related macular degeneration. Following a single intraocular injection of Lucentis (ranibizumab), she developed a subacute cutaneous lupus erythematosus which, with treatment, took nearly 12 months to resolve. This shows that cutaneous lupus erythematosus is a potential side-effect of many medications, including ranibizumab, as in our case and, in an aging population where polypharmacy is a growing reality, clinicians should be aware of how to diagnose and best manage such cases. PMID- 24212216 TI - Isolated complete bitemporal hemianopia in traumatic chiasmal syndrome. AB - A 29-year-old man presented with a chief complaint of lateral blindness in the left eye at 4 months after an accidental fall. His best corrected visual acuity was 0.7 in the left eye and 1.0 in the right eye. Visual field test showed a complete bitemporal hemianopic defect without any neurologic symptoms. An orbital computed tomography scan with non-enhancement conducted at the time of the visit showed multiple frontal skull fractures and cerebromalacia a small fracture in the sphenoidal boneboth frontal lobes. No radiological abnormalities of the visual pathway were detected. Optical coherence showed reduced thickness in the retinal nerve fiber layer, primarily in the superior and inferior part of the left eye. To our knowledge, a complete bitemporal hemianopia without neurological deficits is extremely rare in traumatic chiasmal syndrome. PMID- 24212217 TI - Planned posterior assisted levitation in severe subluxated cataract: surgical technique and clinical results. PMID- 24212225 TI - Changing trends in the prevalence of visual impairment, uncorrected refractive errors and use of spectacles in Mahbubnagar district in South India. AB - BACKGROUND/AIM: The Andhra Pradesh Eye disease Study (APEDS) was a conventional cross-sectional study conducted in four locations during 1996-2000. Ten years later, a Rapid Assessment of Refractive Errors (RARE) survey was conducted in one of the geographical regions. The prevalence of visual impairment (VI), uncorrected refractive error (URE), spectacles use obtained from both the surveys was compared. SETTINGS AND DESIGN: Rural settings; cross-sectional studies. MATERIALS AND METHODS: In both the surveys, distance visual acuity (VA) was assessed using a logMAR chart. Pinhole VA was assessed if presenting VA was <20/20 in APEDS and <20/40 in RARE. VI was defined as presenting VA <20/40 in the better eye. URE was defined as presenting VA <20/40 and improving to >=20/40 with a pinhole. STATISTICAL ANALYSIS USED: Performed using Statistical Package for Social Sciences (SPSS). Chi square tests and t-test were used. RESULTS AND CONCLUSIONS: The results from a RARE survey with 3,095 subjects were compared with an APEDS dataset that had 1,232 subjects in the same age group of 15-49 years. The prevalence of VI has decreased from 9.5% (95% CI, 7.7-11.1) in APEDS to 2.7% (95% CI, 2.1-3.3) in RARE. Similarly, the prevalence of URE in the better eye decreased from 5.8% (95% CI, 4.5-7.1) to 2.3% (95% CI, 1.8-2.8). The usage of spectacles increased from 6.6% (95% CI, 5.2-8.0) to 9.7% (95% CI, 8.7-10.7). There is a decreasing trend in the prevalence of VI and URE in Mahbubnagar district in Andhra Pradesh over a decade. PMID- 24212226 TI - Impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on rabbit retina. AB - BACKGROUND: To observe the impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on the retina in a rabbit model. MATERIALS AND METHODS: Healthy white New Zealand rabbits were randomly assigned into three groups with 20 in each group. Bio-amniotic membranes of 4 * 5 mm immersed in either physiological saline/water for 10 min, or 25 mg/mL 5 fluorouracil solution for 5 and 10 min, respectively, were applied on rabbit eyes during trabeculectomy. At 7, 14, 21, and 28 days of postoperation, five rabbits from each group were examined with electroretinogram (ERG). After being examined for eye pressure and bleb morphology, rabbits were sacrificed by air embolism and their retinas were collected and examined by transmission electron microscopy (TEM). In addition, 5-fluorouracil amount in bio-amniotic membranes was measured using high-performance liquid chromatography. RESULTS: Each bio-amniotic membrane could absorb 59.004 MUg and 75.828 MUg 5-fluorouracil after being immersed in 5 fluorouracil solution for 5 and 10 min, respectively. Application of these bio amniotic membranes in trabeculectomy could promote the formation of well functioning bleb and maintain intraocular pressure, although it had no effect on retina structures as examined with ERG and TEM. CONCLUSION: Application of 5-FU soaked bio-amniotic membrane in rabbit eye trabeculectomy is effective and safe. PMID- 24212227 TI - A novel technique to recanalize the nasolacrimal duct with endodiathermy bipolar probe. AB - AIMS: To evaluate a new approach for recanalization (RC) of nasolacrimal duct obstruction in the treatment of the symptomatic nasolacrimal duct obstruction (NLDO). MATERIALS AND METHODS: A prospective, interventional, comparative study in 302 eyes of 209 patients of symptomatic nontraumatic NLDO. Eyes with previous failed surgery were excluded. One hundred and fifty-one eyes underwent RC with 20 G endodiathermy bipolar probe connected to a 7 W diathermy followed by bicanalicular intubation under direct visualization. One hundred and fifty-one eyes underwent standard external dacryocystorhinostomy (DCR). Follow-up was for 24 months and evaluation was done on basis of change in symptoms and lacrimal syringing. Data was analyzed by Chi-square test and unpaired t-test. P value < 0.05 was considered statistically significant. RESULTS: Success defined as an asymptomatic patient or freely patent syringing was 92.7% (140 eyes) in RC group and 83.44% (126 eyes) in DCR group. Success was significantly more (P <= 0.01) in RC than DCR group. Surgical time was significantly less in RC than DCR (P <= 0.001). In RC group, RC could not be performed in three eyes and had to be later taken up for DCR. Intubation after RC was not achieved in four eyes; however these eyes had a patent pathway till 24 months. Twenty-two eyes had a premature extrusion of the tube; but the success rate in these (20 eyes) was comparable to the others within the group (P > 0.05). Two eyes in RC and one in DCR group had complications. CONCLUSIONS: RC with 20 G endodiathermy bipolar probe is a quick, simple, and effective alternative to standard external DCR. PMID- 24212232 TI - Comparative study of polycyclic aromatic hydrocarbons in coral tissues and the ambient sediments from Kenting National Park, Taiwan. AB - Surface sediments and corals (Acropora sp. and Montipora sp.) from the coastline of Kenting were analyzed in 2009 and 2010 for content levels of polycyclic aromatic hydrocarbons (PAHs) using gas chromatography-mass spectrometry. The total PAH concentrations (t-PAH) in corasls (143-1715 ng g(-1) dw) were significantly higher than in the ambient sediments (2-59 ng g(-1) dw) indicating the bioaccumulation of PAHs in corals. The spatial and seasonal variation in PAH levels suggested that land-loaded contaminants may be the main source of PAHs in the Kenting coral reefs. Based on molecular indices, PAHs were substantially of petroleum origin. The major PAH components were phenanthrene, pyrene and fluorine, but PAH congeners in corals and sediments still have characteristic composition patterns which would be altered by the bio/accumulation mechanisms. Further study is essential to assess and understand the impacts of these chemicals on coral reefs. PMID- 24212233 TI - Spatially-varying surface roughness and ground-level air quality in an operational dispersion model. AB - Urban form controls the overall aerodynamic roughness of a city, and hence plays a significant role in how air flow interacts with the urban landscape. This paper reports improved model performance resulting from the introduction of variable surface roughness in the operational air-quality model ADMS-Urban (v3.1). We then assess to what extent pollutant concentrations can be reduced solely through local reductions in roughness. The model results suggest that reducing surface roughness in a city centre can increase ground-level pollutant concentrations, both locally in the area of reduced roughness and downwind of that area. The unexpected simulation of increased ground-level pollutant concentrations implies that this type of modelling should be used with caution for urban planning and design studies looking at ventilation of pollution. We expect the results from this study to be relevant for all atmospheric dispersion models with urban surface parameterisations based on roughness. PMID- 24212234 TI - Bioaccessibility of metals in alloys: evaluation of three surrogate biofluids. AB - Bioaccessibility in vitro tests measure the solubility of materials in surrogate biofluids. However, the lack of uniform methods and the effects of variable test parameters on material solubility limit interpretation. One aim of this study was to measure and compare bioaccessibility of selected economically important alloys and metals in surrogate physiologically based biofluids representing oral, inhalation and dermal exposures. A second aim was to experimentally test different biofluid formulations and residence times in vitro. A third aim was evaluation of dissolution behavior of alloys with in vitro lung and dermal biofluid surrogates. This study evaluated the bioaccessibility of sixteen elements in six alloys and 3 elemental/metal powders. We found that the alloys/metals, the chemical properties of the surrogate fluid, and residence time all had major impacts on metal solubility. The large variability of bioaccessibility indicates the relevancy of assessing alloys as toxicologically distinct relative to individual metals. PMID- 24212235 TI - Image training, using random images of melanoma, performs as well as the ABC(D) criteria in enabling novices to distinguish between melanoma and mimics of melanoma. AB - Robust experimental evidence supporting many attempts to facilitate early melanoma diagnosis is lacking. In an experimental study using a browser interface we have examined diagnostic accuracy, sensitivity and specificity of novices in distinguishing between melanomas and mimics of melanoma. We show that rule-based ABC methods and image training, based on random images of melanoma, improve specificity to similar degrees, with-out effects on sensitivity, leading to small improvements in overall accuracy. There was a significant effect of age with older subjects performing better. Although both the ABC method and image training groups showed improved performance over the control group, overall performance was poor. For instance, for a task in which 1 in 4 test images was a melanoma, and 3 out of 4 benign, both interventions (ABC or image training) increased accuracy from the control value of 53% to around 61%. For reference, dermatology trainees performed at a much higher level of accuracy. Our study provides little support for the use of such methods in public education, but suggests ways in which performance might be improved. PMID- 24212236 TI - Roles of microRNAs in the hepatitis B virus infection and related diseases. AB - The hepatitis B virus (HBV) is a small enveloped DNA virus that belongs to the Hepadnaviridae family. HBV can cause acute and persistent infection which can lead to hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play a crucial role in the main cellular events. The dysregulation of their expression has been linked to the development of the cancer as well as to viral interference. This chapter will describe the involvement of miRNAs in the case of HBV infection and their implication in the development of the HBV-related diseases. PMID- 24212239 TI - Extracapsular lymph node spread as a negative prognostic factor of adenocarcinoma of the pancreas and cancer of the papilla of vater. AB - OBJECTIVE: The aim of this study was to analyze the incidence and impact of extracapsular lymph node spread (ELNS) in pancreatic cancer (PC) and cancer of the papilla of Vater (CPV). METHODS: Between 2004 and 2009, 148 patients underwent surgical therapy for PC (n = 112) and CPV (n = 36). The resected lymph nodes (LNs) were further analyzed for ELNS. RESULTS: In 95 (64.2%) patients, LN metastasis was present. In 45 (47.3%) of these patients, an ELNS was present on histopathology. The patients' survival was negatively affected by ELNS. For PC, the 5-year survival rate was 37% for patients with no LN metastasis compared with 4% and 0% for patients with LN metastasis (pN1) but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P < 0.001). In patients with CPV, the 5-year survival rate was 56% for patients with no LN metastasis and 44% and 0% for patients with pN1 disease but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P = 0.006). Multivariate analysis revealed ELNS as an independent prognostic factor of survival for both tumor types. CONCLUSIONS: Extracapsular LN spread is an independent negative prognostic factor in PC and CPV. In future staging systems, ELNS should be included. PMID- 24212237 TI - ABCG1-mediated generation of extracellular cholesterol microdomains. AB - Previous studies have demonstrated that the ATP-binding cassette transporters (ABC)A1 and ABCG1 function in many aspects of cholesterol efflux from macrophages. In this current study, we continued our investigation of extracellular cholesterol microdomains that form during enrichment of macrophages with cholesterol. Human monocyte-derived macrophages and mouse bone marrow derived macrophages, differentiated with macrophage colony-stimulating factor (M CSF) or granulocyte macrophage colony-stimulation factor (GM-CSF), were incubated with acetylated LDL (AcLDL) to allow for cholesterol enrichment and processing. We utilized an anti-cholesterol microdomain monoclonal antibody to reveal pools of unesterified cholesterol, which were found both in the extracellular matrix and associated with the cell surface, that we show function in reverse cholesterol transport. Coincubation of AcLDL with 50 MUg/ml apoA-I eliminated all extracellular and cell surface-associated cholesterol microdomains, while coincubation with the same concentration of HDL only removed extracellular matrix associated cholesterol microdomains. Only at an HDL concentration of 200 ug/ml did HDL eliminate the cholesterol microdomains that were cell-surface associated. The deposition of cholesterol microdomains was inhibited by probucol, but it was increased by the liver X receptor (LXR) agonist TO901317, which upregulates ABCA1 and ABCG1. Extracellular cholesterol microdomains did not develop when ABCG1 deficient mouse bone marrow-derived macrophages were enriched with cholesterol. Our findings show that generation of extracellular cholesterol microdomains is mediated by ABCG1 and that reverse cholesterol transport occurs not only at the cell surface but also within the extracellular space. PMID- 24212238 TI - Action myoclonus-renal failure syndrome: diagnostic applications of activity based probes and lipid analysis. AB - Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the GBA gene. While GD is characterized by the presence of glucosylceramide-laden macrophages, AMRF patients do not show these. We studied the fate of GBA in relation to LIMP2 deficiency by employing recently designed activity-based probes labeling active GBA molecules. We demonstrate that GBA is almost absent in lysosomes of AMRF fibroblasts. However, white blood cells contain considerable amounts of residual enzyme. Consequently, AMRF patients do not acquire lipid-laden macrophages and do not show increased plasma levels of macrophage markers, such as chitotriosidase, in contrast to GD patients. We next investigated the consequences of LIMP2 deficiency with respect to plasma glycosphingolipid levels. Plasma glucosylceramide concentration was normal in the AMRF patients investigated as well as in LIMP2-deficient mice. However, a marked increase in the sphingoid base, glucosylsphingosine, was observed in AMRF patients and LIMP2-deficient mice. Our results suggest that combined measurements of chitotriosidase and glucosylsphingosine can be used for convenient differential laboratory diagnosis of GD and AMRF. PMID- 24212240 TI - Pharmacological cholinergic stimulation as a therapeutic tool in experimental necrotizing pancreatitis. AB - OBJECTIVES: The endogenous immune response is influenced by the stimulation of the vagal nerve. Stimulation or ablation has a direct impact on the release of pro- and anti-inflammatory mediators. In the progression of acute pancreatitis from local to systemic disease, these mediators play a pivotal role. This study evaluates the effect of pharmacologic stimulation of the cholinergic system on pancreatic damage in experimental necrotizing pancreatitis. METHODS: Experimental severe necrotizing pancreatitis was induced in male Wistar rats using the glycodeoxycholic acid model. Animals with acute pancreatitis (n = 6) were compared with animals with acute pancreatitis and prophylactic or therapeutic pharmacologic activation of the cholinergic system using nicotine, physostigmine, or neostigmine (n = 36). Twelve hours after the induction of acute pancreatitis, morphological damage as well as the myeloperoxidase levels of the pancreas and the serum levels of high-mobility group box 1 protein were evaluated. RESULTS: Prophylactic and delayed therapeutic application of nicotine, physostigmine, or neostigmine significantly attenuated the severity of acute pancreatitis 12 hours after the induction of severe necrotizing pancreatitis compared with untreated controls as evaluated with histological scores, myeloperoxidase, and high mobility group box 1 levels (P < 0.05). CONCLUSIONS: Stimulation of the cholinergic system is useful to attenuate damage in experimental acute pancreatitis. Not only prophylactic but also delayed application was effective in the present study. PMID- 24212241 TI - Expression of SOX9 in intraductal papillary mucinous neoplasms of the pancreas. AB - OBJECTIVES: SRY (sex determining region Y) box 9 (SOX9) plays a key role in the embryologic development, differentiation, and maintenance of organs in the pancreas as well as progression of several kinds of tumors. The aim of the present study was to evaluate the expression and potential role of SOX9 in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: The authors selected 27 pathological tissues from 19 IPMN cases to assess the expression of SOX9 by means of immunohistochemistry and analyzed the expression pattern of SOX9 with 78 lesions obtained from these tissues stained by SOX9. RESULTS: SOX9 was expressed in the normal pancreas, IPMN, and pancreatic ductal adenocarcinoma. SOX9-positive cells were confined to the lower portions of the papillary structures of IPMN. However, SOX9 was expressed in the entire epithelium once the neoplasms advanced to high-grade dysplasia and invasive carcinoma. The expression pattern of SOX9 was similar to that of CD44 in the normal pancreas and IPMN. Double staining of SOX9 and CD44 detected colocalization of SOX9 and CD44 in IPMN. CONCLUSIONS: Changes in the SOX9 expression pattern may be involved in the mechanisms of the malignant progression of IPMN. PMID- 24212242 TI - Colorimetric and fluorescent pH and Cu2+ probes induced by photoisomerization of a maleonitrile-based Salen ligand. AB - Both photo-induced cis-trans-isomers of a maleonitrile-based Salen ligand can be used as pH probes covering a broad pH range through three different mechanisms but upon undergoing the formation of a stable complex and Cu(2+)-promoted hydrolysis, respectively, they exhibit totally different responses and mechanisms for sensing Cu(2+). PMID- 24212243 TI - High-throughput ultrasonic synthesis and in situ crystallisation investigation of metal phosphonocarboxylates. AB - High-throughput reactions of aqueous solutions of 4-(phosphonomethyl)benzoic acid (H3PMBC) with metal salts were carried out using, for the first time, ultrasonication as well as the previously described conventional heating. On screening the influence of 12 divalent metal ions, two new compounds ([Ca(H2O)2(H2PMBC)2] and [Ni(H2O)4(H2PMBC)2]) were discovered. Their formation fields were established by systematically studying the systems Ni(2+) or Ca(2+)/H3PMBC/KOH. Both compounds crystallise in the space group P1[combining macron] ([Ca(H2O)2(H2PMBC)2]: a = 4.6806(9) A, b = 6.1340(12) A, c = 17.932(4) A, alpha = 83.84(3) degrees , beta = 89.03(3) degrees , gamma = 85.65(3) degrees ; [Ni(H2O)4(H2PMBC)2]: a = 4.7713(10) A, b = 6.8621(14) A, c = 16.598(3) A, alpha = 83.42(3) degrees , beta = 89.71(3) degrees , gamma = 83.50(3) degrees ) and contain MO6-octahedra linked to form chains by hydrogen bonded (H2PMBC(-))2 dimers formed between the carboxylate groups. The formation of [Ni(H2O)4(H2PMBC)2] was studied by in situ EDXRD and in situ IR spectroscopy. The increased formation rate of [Ni(H2O)4(H2PMBC)2] under ultrasonic irradiation as compared to conventional heating could be unequivocally attributed to the faster dissolution of the ligand H3PMBC. PMID- 24212244 TI - Assessment of instrumental activities of daily living in dementia: diagnostic value of the Amsterdam Instrumental Activities of Daily Living Questionnaire. AB - BACKGROUND: Measuring impairments in "instrumental activities of daily living" (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting. METHODS: Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and "disability assessment of dementia" (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses. RESULTS: Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63 0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not. CONCLUSIONS: In this study, we showed a fair diagnostic accuracy for A-IADL Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool. PMID- 24212245 TI - Delusions and hallucinations in persons with dementia: a comparison of the perceptions of formal and informal caregivers. AB - This study compares formal and informal caregivers' perceptions of delusions and hallucinations in older persons with dementia (PWDs). The study population consisted of 151 community-dwelling PWDs aged 65 and older, 90 formal caregivers, and 151 informal caregivers residing in Israel. Assessments included the Behavioral Pathology in Alzheimer's Disease Rating Scale, Neuropsychiatric Inventory, Etiological Assessment of Psychotic Symptoms in Dementia, Activities of Daily Living, and Mini-Mental State Examination. Informal caregivers reported higher rates and a higher level of severity of delusions and hallucinations than formal caregivers. Different caregivers showed varying degrees of emotional involvement, empathy, and efforts to find the meaning of the delusion for the person experiencing it. Family members and staff members may see different parts of the total picture. The combination of both points of view is essential in order to establish an accurate, comprehensive assessment of dementia symptoms and to enhance the understanding of the reality of the different parties. PMID- 24212246 TI - Lower hippocampal volume predicts decrements in lane control among drivers with amnestic mild cognitive impairment. AB - OBJECTIVES: There are few methods to discern driving risks in patients with early dementia and mild cognitive impairment (MCI). We aimed to determine whether structural magnetic resonance imaging (MRI) of the hippocampus-a biomarker of probable Alzheimer pathology and a measure of disease severity in those affected- is linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI. METHODS: In all, 49 consensus-diagnosed participants from an Alzheimer's Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments. RESULTS: Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the patients with MCI (B = 1.63, standard error [SE] = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio and 95% confidence interval for below-optimal lane control in the MCI group was 4.41 (1.18-16.36), which was attenuated to 3.46 (0.88-13.60) after accounting for the contribution of left hippocampal volume. CONCLUSION: These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and Alzheimer disease and whether these could be early markers of clinically meaningful driving risk. PMID- 24212247 TI - Live single cell functional phenotyping in droplet nano-liter reactors. AB - While single cell heterogeneity is present in all biological systems, most studies cannot address it due to technical limitations. Here we describe a nano liter droplet microfluidic-based approach for stimulation and monitoring of surface and secreted markers of live single immune dendritic cells (DCs) as well as monitoring the live T cell/DC interaction. This nano-liter in vivo simulating microenvironment allows delivering various stimuli reagents to each cell and appropriate gas exchanges which are necessary to ensure functionality and viability of encapsulated cells. Labeling bioassay and microsphere sensors were integrated into nano-liter reaction volume of the droplet to monitor live single cell surface markers and secretion analysis in the time-dependent fashion. Thus live cell stimulation, secretion and surface monitoring can be obtained simultaneously in distinct microenvironment, which previously was possible using complicated and multi-step in vitro and in vivo live-cell microscopy, together with immunological studies of the outcome secretion of cellular function. PMID- 24212249 TI - beta-Sialon nanowires, nanobelts and hierarchical nanostructures: morphology control, growth mechanism and cathodoluminescence properties. AB - Morphology control of one dimension (1D) nanomaterials is a pivotal issue in the field of nanoscience research to exploit their novel properties. Herein, we report the morphology controlled synthesis of 1D beta-Sialon nanowires, nanobelts and hierarchical nanostructures via a thermal-chemical vapour deposition process using an appropriately selected catalyst and optimized temperature schedule. Vapour-solid (VS), a combination of vapour-liquid-solid (VLS)-based and VS-tip, and a combination of VS for one-generation nanowires with nucleation, growth and coalescence of two-generation nanobranches (NGCB) are used to explain the growth of beta-Sialon nanowires, nanobelts and hierarchical nanostructures, respectively. Cathodoluminescence measurements show that the individual beta Sialon 1D nanostructures with different morphologies have different luminescent properties. All nanostructures exhibit two distinct emission peaks, the violet/blue emission centered at ~390 nm (3.18 eV), attributable to the near band edge (NBE) emission, and the red emission centered at ~728 nm (1.70 eV), assigned to the deep level (DL) emission. However, the DL emission is the ruling emission in the case of an individual beta-Sialon nanowire, whereas the NBE emission becomes dominant in the case of an individual nanobelt as well as a hierarchical nanostructure due to the size and surface effects. The as-synthesized beta-Sialon with controlled nanostructures and various morphologies can find potential applications in future nanodevices with tailorable or tunable photoelectric properties. PMID- 24212250 TI - Efficient and tunable white-light emission of metal-organic frameworks by iridium complex encapsulation. AB - Metal-organic frameworks (MOFs) are well known for their tunable structure and porosity. Many studies have shown they are promising for various important applications, for which their performance can be further enhanced by encapsulating functional species, such as luminescent guest molecules, within the frameworks. Although numerous MOFs are luminescent, very few emit white light and their quantum yield is usually low. Here we report a strategy to achieve efficient white-light emission by encapsulating an iridium complex in the MOF cavity. A mesoporous blue-emitting MOF is prepared as host to encapsulate a yellow-emitting iridium complex, [Ir(ppy)2(bpy)](+). The resultant composites emit bright white light with good colour quality (for example, Commission International de I'Eclairage coordinates, colour-rendering index and correlated colour temperature of (0.31, 0.33), 84.5 and 5409 K, respectively), and high quantum yield up to 115 degrees C. This strategy may open new perspectives for developing high-performance energy-saving solid-state lighting materials. PMID- 24212252 TI - Bad medicine: gabapentin and pregabalin. PMID- 24212248 TI - Synaptic control of local translation: the plot thickens with new characters. AB - The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics. PMID- 24212254 TI - Immune cells and metabolic dysfunction. AB - Throughout evolution, effective nutrient sensing and control of systemic energy homeostasis have relied on a close physical and functional interaction between immune and metabolically active cells. However, in today's obesogenic environment, this fine-tuned immunometabolic interface is perturbed. As a consequence, chronic inflammatory conditions and aberrant activation of immune cells have emerged as key features of obesity-related metabolic disorders, including insulin resistance, cardiovascular complications, and type 2 diabetes, whereas a major research focus has been placed on the adipocyte-macrophage interaction in the context of metabolic dysfunction; recent studies have not only expanded the scope of relevant immune cells in this setting but also highlight the impact of distinct metabolic organs, including the liver, on immunometabolic control, metabolic disease development, and potential anti-inflammatory therapeutic options in obesity-driven pathologies. This review will thus summarize recent progress in this emerging area of metabolic research. PMID- 24212255 TI - Effect of a robotic restraint gait training versus robotic conventional gait training on gait parameters in stroke patients. AB - Kinematic and kinetic gait parameters have never been assessed following robotic assisted gait training in hemiparetic patients. Previous studies suggest that restraint of the non-paretic lower limb during gait training could be a useful rehabilitation approach for hemiparetic patients. The aim of this study is to compare a new Lokomat((r)) asymmetrical restraint paradigm (with a negative kinematic constraint on the non-paretic limb and a positive kinematic constraint on the paretic limb) with a conventional symmetrical Lokomat((r)) training in hemiparetic subjects. We hypothesized that hip and knee kinematics on paretic side would be more improved after the asymmetrical Lokomat((r)) training than after the conventional training. In a prospective observational controlled study, 26 hemiparetic subjects were randomized to one of the two groups Lokomat((r)) experimental gait training (LE) or Lokomat((r)) conventional gait training (LC). They were assessed using 3D gait analysis before, immediately after the 20 min of gait training and following a 20-min rest period. There was a greater increase in peak knee flexion on the paretic side following LE than LC (p = 0.04), and each type of training induced different changes in vertical GRF during single-support phase on the paretic side. Several other spatiotemporal, kinematic and kinetic gait parameters were similarly improved after both types of training. Lokomat((r)) restrained gait training with a negative kinematic constraint on the non-paretic limb and a positive kinematic constraint on the paretic limb appears to be an effective approach to specifically improve knee flexion in the paretic lower limb in hemiparetic patients. This study also highlights spatiotemporal, kinematic and kinetic improvements after Lokomat((r)) training, in hemiparetic subjects, rarely investigated before. PMID- 24212256 TI - Age-related differences in postural control: effects of the complexity of visual manipulation and sensorimotor contribution to postural performance. AB - Patterns of adaptive changes to the exposure to a sinusoidal visual stimulus can be influenced by stimulus characteristics as well as the integrity of the sensory and motor systems involved in the task. Sensorimotor deficits due to aging might alter postural responses to visual manipulation, especially in more demanding tasks. The purpose of this study was to compare postural control between young and older adults at different levels of complexity and to examine whether possible sensory and/or motor changes account for postural performance differences in older adults. Older and young adults were submitted to the following tests: postural control assessments, i.e., body sway during upright stance and induced by movement of a visual scene (moving room paradigm); sensory assessments, i.e., visual (acuity and contrast sensitivity) and somatosensory (tactile foot sensitivity and detection of passive ankle motion); and motor assessments, i.e., isometric ankle torque and muscular activity latency after stance perturbation. Older adults had worse sensory and motor performance, larger body sway amplitude during stance and stronger coupling between body sway and moving room motion than younger adults. Multiple linear regression analyses indicated that the threshold for the detection of passive ankle motion contributed the most to variances in body sway and this contribution was more striking when visual information was manipulated in a more unpredictable way. The present study suggests that less accurate information about body position is more detrimental to controlling body position, mainly for older adults in more demanding tasks. PMID- 24212253 TI - Immunological aspects of atherosclerosis. AB - Atherosclerosis is a complex chronic inflammatory and metabolic disease that involves the collaboration of several cellular components of the immune system and results in thickening of the arterial wall. Atherosclerosis is also the primary cause of coronary artery and cerebrovascular diseases. A multitude of immune cell subsets, soluble molecules such as chemokines and cytokines, and circulating lipids play pivotal roles in atherosclerosis development. In this review, we highlight the role of the immune system in the course of atherosclerotic disease development and discuss the mechanisms involved. PMID- 24212257 TI - Force control improvements in chronic stroke: bimanual coordination and motor synergy evidence after coupled bimanual movement training. AB - Bimanual movement disorders are common dysfunctions post stroke. This stroke study investigated bimanual force control capabilities to determine the effect of coupled bimanual movement training on bimanual coordination and motor synergy. Stroke participants (N = 11) completed three bimanual force control tasks at 5, 25, and 50 % of maximum voluntary contraction before and after coupled bimanual movement training. Root mean square error (RMSE), approximate entropy, correlation, and bimanual motor synergy were analyzed in two-way completely within-subjects ANOVAs (Test Session * Force Level: 2 * 3). Multiple linear regression analysis determined the relationship between RMSE and other force control measures. The analyses revealed three important findings: (1) RMSE decreased from baseline to posttest (2) negative correlation (e.g., error compensation) and bimanual motor synergy increased at 25 and 50 % after rehabilitation, and (3) increased bimanual motor synergy was strongly associated with decreased RMSE after training. The findings indicate that coupled bimanual movement training improved force control performance, bimanual coordination, and motor synergies. Indeed, the present findings extend bimanual motor synergies as a meaningful indicator for estimating task performance improvements. Finally, bimanual force control is a valid outcome measure in quantifying progress toward motor recovery post stroke. PMID- 24212258 TI - Narrowing the gap: effects of intervention on developmental trajectories in autism. AB - Although still a matter of some debate, there is a growing body of research supporting Early and Intensive Behavioral Intervention as the intervention of choice for children with autism. Learning rate is an alternative to change in standard scores as an outcome measure in studies of early intervention. Learning rates can be displayed graphically as developmental trajectories, which are easy to understand and avoid some of the counter-intuitive properties of changes in standard scores. The data used in this analysis were from 453 children with autism, previously described by Eldevik et al. Children receiving Early and Intensive Behavioral Intervention exhibited significantly steeper developmental trajectories than children in the control group, in both intelligence and adaptive behaviors. However, there was a considerable variability in individual learning rates within the group receiving Early and Intensive Behavioral Intervention. This variability could partly be explained by the intensity of the treatment, partly by children's intake intelligence quotient age-equivalents. Age at intake did not co-vary with learning rate. PMID- 24212259 TI - Health-related quality of life in children with high-functioning autism. AB - The health-related quality of life of school-aged children with high-functioning autism is poorly understood. The objectives of this study were to compare the health-related quality of life of children with high-functioning autism to that of typically developing peers and to compare child-self and parent-proxy reports of health-related quality of life of children. A cross-sectional study of children with high-functioning autism (n = 30) and peers (n = 31) was conducted using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. Children with high-functioning autism had significantly poorer health-related quality of life than peers whether reported by themselves (p < .001) or their parents (p < .001), although disagreement (intra-class coefficient = -.075) between children and parental scores suggested variance in points of view. This study specifically investigated health-related quality of life in children with high-functioning autism as compared to a sample of peers, from the child's perspective. It strengthens earlier findings that children with high-functioning autism experience poorer health-related quality of life than those without this disorder and points to the importance of clinicians working with families to identify areas in a child's life that promote or hinder their sense of well-being. PMID- 24212260 TI - Low serum eicosapentaenoic acid level is a risk for ventricular arrhythmia in patients with acute myocardial infarction: a possible link to J-waves. AB - Eicosapentaenoic acid (EPA) has antiarrhythmic effects. The J-wave on an electrocardiogram is associated with a high incidence of ventricular tachycardia/fibrillation (VT/VF). We evaluated relationships between EPA and J waves, and their involvement in the occurrence of VT/VF in acute myocardial infarction (AMI). Two hundred consecutive patients undergoing successful percutaneous coronary intervention within 12 h after AMI onset were enrolled. Serum EPA level and J-waves at admission were evaluated. The patients were divided into two groups according to the optimal cutoff value (2.94) of serum EPA level (% of total fatty acids): LOW (<2.94, 61 +/- 11 years, n = 103) and HIGH groups (>=2.94, 70 +/- 13 years, n = 81). J-waves were observed more frequently in the LOW (36/103, 35 %) than in HIGH group (16/81, 20 %) (P = 0.020). The 30 day incidence of VT/VF including those occurring before admission was higher in the LOW (19.5 %) than in HIGH group (6.2 %) (P = 0.009). The patients with J waves showed a higher incidence of VT/VF (23.1 %) than those without J-waves (9.9 %) (P = 0.019). Kaplan-Meier analysis showed that the highest incidence of VT/VF was observed in the LOW with J-wave group (27.8 %), followed by the LOW without J wave (15.0 %), HIGH with J-wave (12.5 %), and HIGH without J-wave (4.6 %) (P = 0.013). Cox proportional hazard analysis revealed that Killip grade and low serum EPA level or presence of J-waves were significantly associated with the incidence of VT/VF. Low serum EPA level is a risk for incidence of VT/VF in the acute phase of myocardial infarction. Involvement of the J-wave and its possible link with EPA in the pathogenesis of ischemia-induced VT/VF are suggested. PMID- 24212261 TI - Cognitive impairment in gynecologic cancers: a systematic review of current approaches to diagnosis and treatment. AB - PURPOSE: To review the etiology and assessment of chemotherapy-related cognitive impairment (CRCI). To explore current treatment and prevention strategies for CRCI and propose future research goals in the field of gynecologic oncology. METHODS: Computerized searches in PubMed of cognitive impairment in cancer between 2000 and 2012 were conducted. The inclusion criteria were randomized control trials evaluating treatment of CRCI and search terms 'cognitive function, cognitive impairment, cognitive decline, chemobrain, chemofog, and cancer'. RESULTS: To date, numerous modalities have been utilized for assessing CRCI in patients undergoing therapy. It has been proposed to move towards web-based assessment modalities as a possible standard. Few studies have aimed to elucidate possible treatment and prevention options for CRCI; even less in the field of gynecologic oncology. Only seven of these studies were subjected to randomized control trials. Only one of these studies looked at treatment in patients with gynecologic cancers. CONCLUSIONS: The etiology of CRCI is multi-factorial. Following from this, there is no consensus on the best way to assess CRCI although objective measures are more reliable. One must extrapolate data from the non-gynecologic cancer literature, even venturing to non-cancer literature, to explore the treatment and prevention of CRCI. The methods found in these areas of research have not yet been applied to CRCI in gynecologic oncology. PMID- 24212262 TI - Increased plasma sphingosine-1-phosphate in obese individuals and its capacity to increase the expression of plasminogen activator inhibitor-1 in adipocytes. AB - OBJECTIVES: Concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in obese individuals. One source of PAI-1 is adipocytes. Hypoxia develops within adipose tissue as it expands, presumably contributing to increased levels of sphingosine-1-phosphate (S1P). S1P is a breakdown product of sphingosine, ubiquitous in cell membranes. We have shown previously that S1P increases the expression of PAI-1 in human liver-derived cell line. In the present study, we aimed to determine whether hypoxia induces S1P in adipocytes, thereby potentially contributing to an increase in PAI-1 and hence constraints on fibrinolysis associated with obesity. MATERIALS AND METHODS: Mouse 3T3-L1 adipocytes were exposed to CoCl2 to simulate hypoxia. Assays were performed for PAI-1 mRNA (quantitative PCR) and S1P (high-performance liquid chromatography). RESULTS: The physiologic concentration of S1P increased PAI-1 mRNA expression. The S1P2 receptor antagonist attenuated the increase in PAI-1. Adipocytes expressed sphingosine kinase 1/2 (SPHK1/2) and S1P lyase, key enzymes involved in S1P production and degradation. Hypoxia increased SPHK activity and decreased S1P lyase mRNA. Hypoxia reduced cytosolic sphingosine and increased S1P release into conditioned medium. Inhibitors of ABCA1 and ABCC1 reduced the release of S1P into conditioned media. In obese patients with uncomplicated dyslipidemia and hypertension, plasma S1P was increased compared with that in nonobese and lean individuals. CONCLUSION: Hypoxia in adipose tissue of obesity can promote elaboration of S1P that binds to S1P2 receptors in an autocrine or a paracrine manner. S1P potentially contributes toward increased expression of PAI-1 and consequent constraints on fibrinolysis. S1P production and extracellular transport provide an attractive target for therapy to attenuate impaired fibrinolysis associated with obesity. PMID- 24212263 TI - Autophagy of monocytes attenuates the vulnerability of coronary atherosclerotic plaques. AB - OBJECTIVE: The aim of this study was to determine whether autophagy of monocytes attenuates the vulnerability of atherosclerotic plaques. METHODS: The study group comprised 50 patients with stable angina pectoris (SAP), 50 patients with unstable angina pectoris (UAP), 40 patients with acute myocardial infarction (AMI), and 30 patients without coronary artery disease (control). Peripheral blood monocytes (PBMs) were isolated and the expression levels of the proteins beclin-1 and light chain 3 (LC3) (autophagy-specific proteins) in the PBMs were analyzed by western blot. A laser scanning confocal microscope was used to determine the levels of LC3 in the PBMs. RESULTS: Western blot analysis revealed that the expression of beclin-1 and LC3 was significantly lower in acute coronary syndrome patients than in the SAP and control groups (P<0.05). Among the acute coronary syndrome patients, the expression level of beclin-1 and LC3 in the AMI group was significantly decreased compared with that in the UAP group (P<0.05). However, there was no statistical difference between the SAP group and the control group. The results of immunofluorescence assays showed that the fluorescence intensity of LC3 in the PBMs of AMI patients was significantly lower than that in those of UAP patients (P<0.05), which was also significantly decreased compared with that in those of SAP patients and the control group (P<0.05). Expression levels of beclin 1 in the UAP and AMI groups had a negative linear correlation with C-reactive protein levels (r=-0.531, P<0.05; r=-0.589, P<0.05, respectively). CONCLUSION: Autophagy of PBMs is involved in the pathogenesis of plaque vulnerability and subsequent plaque rupture. Enhancing the autophagy of PBMs may be a new therapeutic target for stabilizing atherosclerotic plaques. PMID- 24212265 TI - Probing the metallating ability of a polybasic sodium alkylmagnesiate supported by a bulky bis(amido) ligand: deprotomagnesiation reactions of nitrogen-based aromatic substrates. AB - Exploring the reactivity of sodium butylmagnesiate reagent [{Na(THF)6}(+){(Ph2Si(NAr*)2)Mg(Bu)(THF)}(-)] (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}(2-) (Ar* = 2,6-iPr2-C6H3) towards N-methylbenzimidazole (bIm(Me)), pyrrole and 2,6-diisopropylaniline (NH2Ar*), this study provides new insights into the ability of this bimetallic base to facilitate direct Mg-H exchange reactions as well as to exhibit polybasicity. Thus 1 effectively promotes the deprotomagnesiation of bIm(Me) under mild reaction conditions to give the alpha-metallated intermediate [{Na(THF)5}2(+){(Ph2Si(NAr*)2)Mg(bIm(Me)*)}2(-)] (2) (bIm(Me)* = 2-N methylbenzimidazolyl). Analysis of crystallographic and NMR data of 2 combined with DFT calculations show that the metallated C in the bIm(Me)* ligands possesses a significant carbenic character. Contrasting with previous studies of benzothiazole (btz), 1 does not react with an excess of bIm(Me) even under forcing refluxing conditions. Contrastingly, the amination reactions of equimolar amounts of 1 with pyrrole and 2,6-diisopropylaniline allowed the isolation of [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] (3) and [{Na(THF)6}(+){(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}(-)] (4) respectively as crystalline solids. Highlighting the ability of 1 to act as a polybasic reagent, 3 and 4 are formed as the result of the deprotonation of two molecules of the relevant amine via its butyl group and one amido arm of the silyl(bisamido) ligand. Similarly, the reactions of 1 with 3 molar equivalents of the relevant amine yielded homoleptic tris(amido) compounds [(THF)2NaMg(NC4H4)3] (5) and [{Na(THF)6}(+){Mg(NHAr*)3}(-)] (7), with the concomitant formation of bis(amine) Ph2Si(NHAr)2, as a result of the complete amination of 1 using its three basic sites. The structures in the solid state of 3 and 4 were elucidated by X-ray crystallography. Despite their similar constitution, these heteroleptic tris(amido)magnesiates adopt contrasting structures, with the former displaying a contacted ion-pair structure, where Na and Mg are connected by two bridging pyrrolyl anions, whereas the latter gives rise to a solvent-separated ion pair motif. To the best of our knowledge 3 represents the first crystallographically characterized magnesium compound containing an anionic non-substituted form of pyrrole. Noticeably, Mg interacts exclusively with the N atoms of the pyrrolyl ligands, forming strong sigma-bonds, whereas Na prefers to engage with the pi systems of both NC4-rings. PMID- 24212264 TI - Newly diagnosed and previously known diabetes mellitus and short-term outcomes in patients with acute myocardial infarction. AB - OBJECTIVES: The prognostic value of diabetes mellitus (DM) on the long-term outcomes of patients after myocardial infarction has been well established. The correlation between DM, including newly diagnosed DM, and short-term outcomes needs to be validated. PATIENTS AND METHODS: A total of 5410 ST-segment elevation myocardial infarction (STEMI) patients with typical chest pain onset in the past 12 h were enrolled. Follow-ups were carried out on days 7 and 30 after hospital admission. According to 2013 Standards of Medical Care in Diabetes, the study population was stratified into the following three groups: no diabetes, newly diagnosed diabetes, and previously known diabetes. The primary outcomes of our study were mortality from all causes and major adverse cardiac events (MACE) at days 7 and 30. RESULTS: Patients with previously known diabetes were older and had a higher incidence of previous history of cardiovascular disease compared with the other groups. The 7-day and 30-day mortality was similar between patients without DM and patients with newly diagnosed DM. For both groups, this was significantly lower than that in patients with DM. Similar results were observed for 7-day and 30-day MACE. Multivariable Cox regression analysis indicated that newly diagnosed diabetes did not correlate with 30-day MACE (hazard ratio, 0.901; 95% confidence interval, 0.759-1.069), but that previously known DM correlated with short-term MACE (hazard ratio, 1.211; 95% confidence interval, 1.009-1.453). CONCLUSION: Previously known DM, but not newly diagnosed DM, was an independent predictor for short-term MACE in patients with STEMI. To reduce the incidence of short-term MACE and the detrimental effects of stress hyperglycemia after STEMI, intensive insulin therapy should be provided to diabetic patients with STEMI. PMID- 24212266 TI - The induction of phenylpropanoid biosynthetic enzymes by ultraviolet light or fungal elicitor in cultured parsley cells is overriden by a heat-shock treatment. AB - The normal (25 degrees C) response of parsley (Petroselinum crispum Mill.) cell suspension cultures to ultraviolet (UV) light was suppressed by a simultaneous 37 degrees C heat-shock treatment, as indicated by the loss of the inducibility of two enzymes of flavonoid biosynthesis, phenylalanine ammonia-lyase (EC 4.3.1.5) and chalcone synthase. The effects on enzyme activity and on enzyme synthesis in vitro and in vivo were similar, indicating that regulatory control is at an early step of gene expression, presumably transcription. When heat shock was given during the course of an ongoing UV induction, both enzyme synthesis and enzyme activities ceased rapidly. Likewise, the induction of phenylalanine ammonia-lyase by an elicitor from Phytophthora megasperma f. sp. glycinea was terminated upon transfer from 25 degrees C to 37 degrees C. Based on these and previously published data, it is concluded that stress responses in this system are preferentially expressed in the order of heat shock, fungal elicitor and UV light. PMID- 24212267 TI - Charge and acidity compensation during proton-sugar symport in Chlorella: The H(+)-ATPase does not fully compensate for the sugar-coupled proton influx. AB - This study was undertaken in order to demonstrate the extent to which the activity of the plasmalemma H(+)-ATPase compensates for the charge and acidity flow caused by the sugar-proton symport in cells of chlorella vulgaris Beij.. Detailed analysis of H(+) and K(+) fluxes from and into the medium together with measurements of respiration, cytoplasmic pH, and cellular ATP-levels indicate three consecutive phases after the onset of H(+) symport. Phase 1 occurred immediately after addition of sugar, with an uptake of H(+) by the hexoseproton symport and charge compensation by K(+) loss from the cells and, to a smaller degree, by loss of another ion, probably a divalent cation. This phase coincided with strong membrane depolarization. Phase 2 started approximately 5 s after addition of sugar, when the acceleration of the H(+)-ATPase caused a slow-down of the K(+) efflux, a decrease in the cellular ATP level and an increase in respiration. The increased respiration was most probably responsible for a pronounced net acidification of the medium. This phase was inhibited in deuterium oxide. In phase 3, finally, a slow rate of net H(+) uptake and K(+) loss was established for several further minutes, together with a slight depolarization of the membrane. There was hardly any pH change in the cytoplasm, because the cytoplasmic buffering capacity was high enough to stabilize the pH for several minutes despite the net H(+) fluxes. The quantitative participation of the several phases of H(+) and K(+) flow depended on the pH of the medium, the ambient Ca(2+) concentration, and the metabolic fate of the transported sugar. The results indicate that the activity of the H(+)-ATPase never fully compensated for H(+) uptake by the sugar-symport system, because at least 10% of symport caused charge inflow was compensated for by K(+) efflux. The restoration of pH in the cytoplasm and in the medium was probably achieved by metabolic reactions connected to increased glycolysis and respiration. PMID- 24212268 TI - Ultrastructural localization of photosynthetic activity in thylakoids during chloroplast development in maize. AB - The localization of photosynthetic activity in developing maize (Zea mays L.) chloroplasts was studied in situ by two electron-microscopic-cytochemical methods. The activity of photosystem I was detected by photooxidation of 3,3' diaminobenzidine (DAB) and the activity of the photosystem II by photoreduction of thiocarbamyl nitrotetrazolium blue (TCNBT). During the transformation of proplastids into chloroplasts, at the base of the leaf blade the DAB reaction appeared before the TCNBT reaction. A positive DAB reaction was observed in the single thylakoids of plastids in cells located only about 0.5 mm above the base. Dark, osmiophilic DAB polymers accumulated in the lumina of the thylakoids. Plastid envelopes and tubules of the prolamellar bodies in immature chloroplasts were DAB-negative. In fully differentiated leaf tissue the DAB reaction was intense in the thylakoids of bundle-sheath chloroplasts, as well as in the stroma thylakoids and the peripheral grana thylakoids of mesophyll chloroplats. The photoreduction of TCNBT started in leaf tissue about 1 mm above the base. Dark granular material of reduced TCNBT appeared mostly in the partitions of grana, i.e. interthylakoidally, but some granules were also attached to the stroma thylakoids. The membranes of plastid envelopes and the tubules of prolamellar bodies showed a negative TCNBT reaction. Young bundle-sheath chloroplasts contained some reduced TCNBT in their grana; these deposits largely disappeared in the course of further differentiation. In mature leaf tissue the photoreduction of TCNBT was conspicuous in the grana of mesophyll chloroplasts, but very weak in the single thylakoids and in the granal rudiments of bundle sheath chloroplasts. PMID- 24212269 TI - The cell wall-plasmalemma interface in sieve tubes of barley. AB - Both thick- and thin-walled sieve tubes in leaf-blade veins of Hordeum vulgare L. exhibit a distinct, electron-opaque inner wall layer after fixation in glutaraldehyde-osmium tetroxide and staining with uranyl acetate and lead citrate. This inner wall layer is thickest at the sieve plates and lateral sieve areas where it is permeated by a labyrinth of tubules formed by the plasmalemma. Along the lateral walls between sieve areas the inner wall layer apparently is penetrated by numerous microvilli-like evaginations of the plasmalemma, giving the cell wall-plasmalemma interface the appearance of a brush border. It is suggested that a similar brush-border-like structure may occur at the cell wall plasmalemma interface of sieve elements in a wide variety of vascular plants. PMID- 24212270 TI - Cell water potential, osmotic potential, and turgor in the epidermis and mesophyll of transpiring leaves : Combined measurements with the cell pressure probe and nanoliter osmometer. AB - Water potential, osmotic potential and turgor measurements obtained by using a cell pressure probe together with a nanoliter osmometer were compared with measurements obtained with an isopiestic psychrometer. Both types of measurements were conducted in the mature region of Tradescantia virginiana L. leaves under non-transpiring conditions in the dark, and gave similar values of all potentials. This finding indicates that the pressure probe and the osmometer provide accurate measurements of turgor, osmotic potentials and water potentials. Because the pressure probe does not require long equilibration times and can measure turgor of single cells in intact plants, the pressure probe together with the osmometer was used to determine in-situ cell water potentials, osmotic potentials and turgor of epidermal and mesophyll cells of transpiring leaves as functions of stomatal aperture and xylem water potential. When the xylem water potential was-0.1 MPa, the stomatal aperture was at its maximum, but turgor of both epidermal and mesophyll cells was relatively low. As the xylem water potential decreased, the stomatal aperture became gradually smaller, whereas turgor of both epidermal and mesophyll cells first increased and afterward decreased. Water potentials of the mesophyll cells were always lower than those of the epidermal cells. These findings indicate that evaporation of water is mainly occurring from mesophyll cells and that peristomatal transpiration could be less important than it has been proposed previously, although peristomatal transpiration may be directly related to regulation of turgor in the guard cells. PMID- 24212271 TI - Actin cytoskeleton in intact and wounded coenocytic green algae. AB - The subcellular distribution of actin was investigated in two related species of coenocytic green algae, with immunofluorescence microscopy. Either no, or fine punctate fluorescence was detected in intact cells of Ernodesmis verticillata (Kutzing) Borgesen and Boergesenia forbesii (Harvey) Feldmann. A reticulate pattern of fluorescence appears throughout the cortical cytoplasm of Ernodesmis cells shortly after wounding; this silhouettes chloroplasts and small vacuoles. Slender, longitudinal bundles of actin become evident in contracting regions of the cell, superimposed over the reticulum. Thicker portions of the bundles were observed in well-contracted regions, and the highly-convoluted appearance of nearby cortical microtubules indicates contraction of the bundles in these thicker areas. Bundles are no longer evident after healing; only the reticulum remains. In Boergesenia, a wider-mesh reticulum of actin develops in the cortex of wounded cells, which widens further as contractions continue. Cells wounded in Ca(2+)-free medium do not contract, and although the actin reticulum is apparent, no actin bundles were ever observed in these cells. Exogenously applied cytochalasins have no effect on contractions of cut cells or extruded cytoplasm, and normal actin-bundle formation occurs in treated cells. In contrast, erythro-9 [3-(2-hydroxynonyl)]adenine (EHNA) completely inhibits longitudinal contractions in wounded cells, and few uniformly slender actin bundles develop in inhibited cells. These results indicate that wounding stimulates a Ca(2+)-dependent, hierarchical assembly of actin into bundles, whose assembly and functioning are inhibited by EHNA. Contraction of the bundles and concomitant wound healing are followed by cessation of motility and disassembly of the bundles. The spatial and temporal association of the bundles with regions of cytoplasmic contraction, indicates that the actin bundles are directly involved in wound-induced cytoplasmic motility in these algae. PMID- 24212272 TI - Rapid induction of phenylalanine ammonia-lyase and chalcone synthase mRNAs during fungus infection of soybean (Glycine max L.) roots or elicitor treatment of soybean cell cultures at the onset of phytoalexin synthesis. AB - The differential regulation of the activities and amounts of mRNAs for two enzymes involved in isoflavonoid phytoalexin biosynthesis in soybean was studied during the early stages after inoculation of primary roots with zoospores from either race 1 (incompatible, host resistant) or race 3 (compatible, host susceptible) of Phytophthora megasperma f.sp. glycinea, the causal fungus of root rot disease. In the incompatible interaction, cloned cDNAs were used to demonstrate that the amounts of phenylalanine ammonia-lyase and chalcone synthase mRNAs increased rapidly at the time of penetration of fungal germ tubes into epidermal cell layers (1-2 h after inoculation) concomitant with the onset of phytoalxxin accumulation; highest levels were reached after about 7 h. In the compatible interaction, only a slight early enhancement of mRNA levels was found and no further increase occurred until about 9 h after inoculation. The time course for changes in the activity of chalcone synthase mRNA also showed major differences between the incompatible and compatible interaction. The observed kinetics for the stimulation of mRNA expression related to phytoalexin synthesis in soybean roots lends further support to the hypothesis that phytoalexin production is an early defense response in the incompatible plant-fungus interaction. The kinetics for the enhancement of mRNA expression after treatment of soybean cell suspension cultures with a glucan elicitor derived from P. megasperma cell walls was similar to that measured during the early stages of the resistant response of soybean roots. PMID- 24212273 TI - A kinematic analysis of tepal growth in Lilium longiflorum. AB - Time-lapse marking experiments indicate that the growth of tepals in Lilium longiforum Thunb. from 3.7 mm to maturity is triphasic. Phase I (tepal lengths 3.7-10 mm) is characterized by spatial and temporal variation in growth rate and, in the epidermis, a random distribution of mitoses with an acropetal increase in cell area. During phase II (10-90 mm) cell elongation and (later) cell division is restricted largely to basal regions. Cell division ceases when tepals are less than one-third of their mature length of 155 mm. Phase III (90-155 mm) is characterized by the gradual transition from basal to apical growth, and a modification of epidermal cell shape. A sharp peak in growth at the extreme tip of the tepal coincides with anthesis. PMID- 24212274 TI - Effect of nitrate, ammonium, light and a plastidic factor on the appearance of multiple forms of nitrate reductase in mustard (Sinapis alba L.) cotyledons. AB - In mustard (Sinapis alba L.) cotyledons, four different forms of nitrate reductase (NR) can be separated by anion-exchange chromatography. Two of these forms (NR1 and NR2) appear in the presence of NO 3 (-) while the other two (NR3 and NR4) appear as a response to the application of NH 4 (+) as the sole nitrogen source. In the presence of NH4NO3, NR3 appears to be superimposed on nitrate induced NR1 and NR2 while the NH 4 (+) -induced appearance of NR4 is totally abolished in the presence of equimolar amounts of NO 3 (-) . The appearance of NR1, NR2 and NR3 is strongly stimulated by red light pulses which operate via the far-red-absorbing form of phytochrome (Pfr), whereas the appearance of NR4 requires continuous light (likewise operating through pytochrome). Continuous red light is more effective in this case than continuous far-red light. Analysis of the data shows that the mode of action of phytochrome (Pfr) is the same in the case of the appearances of NR1 and NR2, whereas it is quantitatively different in the case of NR3 and totally different in that of NR4. A 'plastidic factor' has previously been postulated to be obligatorily involved in the transcriptional control of nuclear genes encoding for proteins destined for the chloroplast. Photooxidative damage of the plastid is postulated to destroy the ability of the organelle to produce this signal. If the plastids are damaged by photooxidation, the action of nitrate and phytochrome on the appearance of NR is abolished. The plant cell regulates the appearance of nitrate-induced NR, which is cytosolic, as if it were a plastidic protein. The appearance of NR3 depends on the plastidic factor in principally the same way as that of NR1 and NR2 whereas NR4 is totally independent of the plastidic factor. The data document particular kinds of interaction between controlling factors (light, nitrate, ammonium, plastidic factor) which affect gene expression in plants. These intricacies of regulation have so far not been considered in molecular studies on NR-gene expression. PMID- 24212275 TI - Effect of dehydration and high light on photosynthesis of two C3 plants (Phaseolus vulgaris L. and Elatostema repens (Lour.) Hall f.). AB - The effect of drought on the photosynthetic functioning of two C3 plants, Phaseolus vulgaris and Elatostema repens, has been examined. Leaf net CO2 uptake measured in normal air was negligible at a leaf water deficit of about 30% while the calculated leaf intercellular CO2 concentration (Ci) was unchanged. However, both the maximal photosynthetic capacity (CO2-dependent O2 evolution) and apparent quantum yield, measured in the presence of saturating CO2 levels (5 to 14%), only started to decrease within the range of 25 to 30% leaf water deficit. This shows that the drought-induced inhibition seen in normal air is not caused by an inhibition of the photosynthetic mechanism, and that in this case Ci values can be misleading. Both 77 K and room-temperature fluorescence measurements indicate that the functioning of the photosystem-II reaction centre is hardly modified by water shortage. Furthermore, an analysis of photochemical chlorophyll fluorescence quenching shows, in the absence of CO2, that O2 can be an efficient acceptor of photosynthetic energy, even in severly dehydrated plants which do not show net CO2 uptake in normal air. In these plants, O2 is probably reduced mainly via Mehler-type reactions. High-light treatment given at low O2 increases photoinhibition as measured by the decrease of apparent quantum yield in dehydrated P. vulgaris, whereas, interestingly, 1% O2 protects dehydrated E. repens against high-light damage. The two plants could have different protective mechanisms depending upon the O2 level or different photoinhibitory sites or mechanisms. PMID- 24212276 TI - Light and the maintenance of photosynthetic competence in leaves of Populus balsamifera L. during short-term exposures to high concentrations of sulfur dioxide. AB - Leaves of Populus balsamifera grown under full natural sunlight were treated with 0, 1, or 2 MUl SO2.1(-1) air under one of four different photon flux densities (PFD). When the SO2 exposures took place in darkness or at 300 MUmol photons.m( 2).s(-1), sulfate accumulated to the levels predicted by measurements of stomatal conductance during SO2 exposure. Under conditions of higher PFD (750 and 1550 MUmol.m(-2).s(-1)), however, the predicted levels of accumulated sulfate were substantially higher than those obtained from anion chromatography of the leaf extracts. Light-and CO2-saturated capacity as well as the photon yield of photosynthetic O2 evolution were reduced with increasing concentration of SO2. At 2 MUl SO2.1(-1) air, the greatest reductions in both photosynthetic, capacity and photon yield occurred when the leaves were exposed to SO2 in the dark, and increasingly smaller reductions in each occurred with increasing PFD during SO2 exposure. This indicates that the inhibition of photosynthesis resulting from SO2 exposure was reduced when the exposure occurred under conditions of higher light. The ratio F v/F M (variable/maximum fluorescence emission) for photosyntem II (PSII), a measure of the photochemical efficiency of PSII, remained unaffected by exposure of leaves to SO2 in the dark and exhibited only moderate reductions with increasing PFD during the exposure, indicating that PSII was not a primary site of damage by SO2. Pretreatment of leaves with SO2 in the dark, however, increased the susceptibility of PSII to photoinhibition, as such pretreated leaves exhibited much greater reductions inF V/F M when transferred to moderate or high light in air than comparable control leaves. PMID- 24212277 TI - Sites of synthesis, translocation and accumulation of pyrrolizidine alkaloid N oxides in Senecio vulgaris L. AB - (14)C-Labelled alkaloid precursors (arginine, putrescine, spermidine) fed to Senecio vulgaris plants via the root system were rapidly taken up and efficiently incorporated into the pyrrolizidine alkaloid senecionine N-oxide (sen-Nox) with total incorporations of 3-6%. Considerable amounts of labelled sen-Nox were translocated into the shoot and were directed mainly into the inflorescences, the major sites of pyrrolizidine-alkaloid accumulation. Detached shoots of S. vulgaris were unable to synthesize pyrrolizidine alkaloids, indicating that the roots are the site of their biosynthesis. Further evidence was obtained from studies with in-vitro systems established from S. vulgaris: root cultures were found to synthesize pyrrolizidine alkaloids but not cell-suspension cultures, tumor cultures or shoot-like teratomas obtained by transformation with Agrobacterium tumefaciens. Studies on transport of [(14)C]sen-Nox, which was fed either to detached shoots or to the root system of intact plants, indicate that the alkaloid N-oxide does not simply follow the transpiration stream but is specifically channelled to the target tissues such as epidermal stem tissue and flower heads. Exogenously applied [(14)C]senecionine is rapidly N-oxidized. If the phloem path along the stem is blocked by a "steam girdle" translocation of labelled sen-Nox is blocked as well. Root-derived sen-Nox accumulated below the girdle and only trace amounts were found in the tissues above. It is most likely that the root-to-shoot transport of sen-Nox occurs mainly if not exclusively via the phloem. In accordance with previous studies the polar, salt-like N-oxides, which are often considered to be artifacts, were found to be the real products of pyrrolizidine-alkaloid biosynthesis as well as the physiological forms for long distance transport, tissue-specific distribution and cellular accumulation. PMID- 24212278 TI - Enzymes from seeds of Phaseolus vulgaris L.: Hydroxylation of gibberellins A20 and A 1 and 2,3-dehydrogenation of gibberellin A 20. AB - A time-course study is described relating the enzyme activities for GA20 metabolism with seed development in Phaseolus vulgaris L. Enzyme activity for the 3beta-hydroxylation of GA20 to GA1, and for the 2,3-desaturation of GA20 to GA5, was confined to the cotyledons and showed maximal specific activity at 21 d after anthesis. These enzyme activities co-occurred, together with a much lower level of activity for the 2beta-hydroxylation of GA20 to GA29. The observed rates of GA1, GA5 and GA29 formation from GA20 were constant under a range of incubation conditions. Enzyme activity for the conversion of GA1 to GA8 was detected only in embryos of seed from 40 d after anthesis. By deuterium-labelling and analysis of the products by gas chromatography-selected ion monitoring it was shown that 2beta-hydroxylation of GA1 to GA8 and 3beta-hydroxylation of GA20 to GA1 occur with retention of configuration and that the conversion of GA20 to GA5 occurs with loss of the 2beta- and 3beta-hydrogens. These results establish that GA1 is not formed from GA20 via GA5. PMID- 24212279 TI - Regulation of sucrose-phosphate-synthase activity in spinach leaves by protein level and covalent modification. AB - A dot-blot technique was developed using monoclonal antibodies to measure, rapidly and accurately, the amount of sucrose-phosphate synthase (SPS; EC 2.4.1.14) protein present in a crude extract from spinach (Spinacia oleracea L. cv. Dark Green Bloomsdale) leaves; this was compared with SPS activity in this material. During leaf development, increased SPS activity followed closely the increase in enzyme-protein level, indicating denovo synthesis or altered turn over rates for SPS. In contrast, activation of SPS by illumination of leaves or by mannose treatment of leaf discs in the dark (M. Stitt et al. Planta 174, 217 230) occurred without a significant change in the level of enzyme protein. Since conditions which altered SPS activity did not affect immunoprecipitation or mobility of the 120-kilodalton (kDa) subunit of the enzyme during denaturing gel electrophoresis, some form of protein modification other than proteolysis must be involved. Overall, the results indicate that regulation of SPS activity can involve changes in the level of enzyme protein and-or covalent modification. PMID- 24212280 TI - Characterization of long-term extension of isolated cell walls from growing cucumber hypocotyls. AB - Walls from frozen-thawed cucumber (Cucumis sativus L.) hypocotyls extend for many hours when placed in tension under acidic conditions. This study examined whether such "creep" is a purely physical process dependent on wall viscoelasticity alone or whether enzymatic activities are needed to maintain wall extension. Chemical denaturants inhibited wall creep, some acting reversibly and others irreversibly. Brief (15 s) boiling in water irreversibly inhibited creep, as did pre-incubation with proteases. Creep exhibited a high Q10 (3.8) between 20 degrees and 30 degrees C, with slow inactivation at higher temperatures, whereas the viscous flow of pectin solutions exhibited a much lower Q10 (1.35). On the basis of its temperature sensitivity, involvement of pectic gel-sol transitions was judged to be of little importance in creep. Pre-incubation of walls in neutral pH irreversibly inactivated their ability to creep, with a half-time of about 40 min. At 1 mM, Cu(2+), Hg(2+) and Al(3+) were strongly inhibitory whereas most other cations, including Ca(2+), had little effect. Sulfhydryl-reducing agents strongly stimulated creep, apparently by stabilizing wall enzyme(s). The physical effects of these treatments on polymer interactions were examined by Instron and stress-relaxation analyses. Some treatments, such as pH and Cu(2+), had significant effects on wall viscoelasticity, but others had little or no apparent effect, thus implicating an enzymatic creep mechanism. The results indicate that creep depends on relatively rugged enzymes that are firmly attached to or entangled in the wall. The sensitivity of creep to SH-reducing agents indicates that thiol reduction of wall enzymes might provide a control mechanism for endogenous cell growth. PMID- 24212282 TI - Erratum. PMID- 24212281 TI - X-ray microanalysis of ion distribution within root cortical cells of the halophyte Suaeda maritima (L.) Dum. AB - The ion content of compartments within cortical cells of mature roots of the halophyte Suaeda maritima grown at 200 mol.m(-3) NaCl has been studied by X-ray microanalysis of freeze-substituted thin sections. Sodium and Cl were found in the vacuoles at about four-times the concentration in the cytoplasm or cell walls, whereas K was more concentrated in the cell walls and cytoplasm than in vacuoles. The vacuolar Na concentration was 12- to 13-times higher than that of K. The Na concentration of cell walls of cortical cells was about 95 mol.m(-3) of analysed volume. The cytoplasmic K concentration within the mature cortical cells was estimated to be 55 mol.m(-3) of analysed volume. PMID- 24212283 TI - Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses. AB - Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses. PMID- 24212284 TI - Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU. AB - OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 +/- 0.91 to 0.87 +/- 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 +/- 30.0 to 70.6 +/- 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions. PMID- 24212285 TI - Characterization and analysis of a transcriptome from the boreal spider crab Hyas araneus. AB - Research investigating the genetic basis of physiological responses has significantly broadened our understanding of the mechanisms underlying organismic response to environmental change. However, genomic data are currently available for few taxa only, thus excluding physiological model species from this approach. In this study we report the transcriptome of the model organism Hyas araneus from Spitsbergen (Arctic). We generated 20,479 transcripts, using the 454 GS FLX sequencing technology in combination with an Illumina HiSeq sequencing approach. Annotation by Blastx revealed 7159 blast hits in the NCBI non-redundant protein database. The comparison between the spider crab H. araneus transcriptome and EST libraries of the European lobster Homarus americanus and the porcelain crab Petrolisthes cinctipes yielded 3229/2581 sequences with a significant hit, respectively. The clustering by the Markov Clustering Algorithm (MCL) revealed a common core of 1710 clusters present in all three species and 5903 unique clusters for H. araneus. The combined sequencing approaches generated transcripts that will greatly expand the limited genomic data available for crustaceans. We introduce the MCL clustering for transcriptome comparisons as a simple approach to estimate similarities between transcriptomic libraries of different size and quality and to analyze homologies within the selected group of species. In particular, we identified a large variety of reverse transcriptase (RT) sequences not only in the H. araneus transcriptome and other decapod crustaceans, but also sea urchin, supporting the hypothesis of a heritable, anti-viral immunity and the proposed viral fragment integration by host-derived RTs in marine invertebrates. PMID- 24212286 TI - Characterization of the host-defense peptides from skin secretions of Merlin's clawed frog Pseudhymenochirus merlini: insights into phylogenetic relationships among the Pipidae. AB - The family Pipidae comprises the genera Hymenochirus, Pipa, Pseudhymenochirus, Silurana, and Xenopus but phylogenetic relationships within the family are unclear. Peptidomic analysis of norepinephrine-stimulated skin secretions from Pseudhymenochirus merlini Chabanaud, 1920, the single species within the genus Pseudhymenochirus, led to identification of 13 host-defense peptides with antimicrobial activity. Two peptides (hymenochirin-1Pa and -1Pb) show structural similarity to hymenochirin-1B from Hymenochirus boettgeri and eight peptides (hymenochirin-5Pa, -5Pb, -5Pc, -5Pd, -5Pe, -5Pf, 5Pg and -5Ph) are structurally similar to each other and to hymenochirin-5B from H. boettgeri. Two peptides differing by a single amino acid (IKIPSFFRNILKKVGKEAVSLM/I AGALKQS), termed pseudhymenochirin-1Pa and -1Pb, and pseudhymenochirin-2Pa (GIFPIFAKLLGKVIKVASSLISKGRTE) do not resemble host-defense peptides previously isolated from pipid frogs. Hymenochirin-5Pe was the most abundant peptide in the secretions and hymenochirin-1Pa the most potent against Staphylococcus aureus (MIC=2.5MUM) and Escherichia coli (MIC=10MUM). The data support a close phylogenetic relationship between Hymenochirus and Pseudhymenochirus that is distinct from the Xenopodinae (Xenopus+Silurana) clade with Pipa sister-group to all other extant pipids. PMID- 24212287 TI - CryomiRs: towards the identification of a cold-associated family of microRNAs. AB - Hypometabolism is a strategy favored by many species to survive extreme environmental stresses such as low temperatures, lack of food sources or anoxic conditions. Mammalian hibernation and insect cold hardiness are well-documented examples of natural models utilizing metabolic rate depression when confronted with such conditions. A plethora of metabolic and molecular changes must occur in these species to regulate this process. A recently discovered family of short non coding nucleic acids, the miRNAs, is rapidly emerging as a potential modulator of cold tolerance in different species. In this review, we present the current knowledge associated with physiological and biochemical adaptations at low temperatures. We further explore the cascade of miRNA biogenesis as well as miRNA target recognition and translational repression. Finally, we introduce miRNAs shown to be differentially regulated in selected species when confronted with low temperatures and discuss the potential transcript targets regulated by these "CryomiRs". PMID- 24212288 TI - Risk of Kaposi sarcoma among immigrants to Sweden. PMID- 24212289 TI - Diagnosis and treatment of primary lymphedema. Consensus document of the International Union of Phlebology (IUP)-2013. AB - Primary lymphedema can be managed effectively as a form of chronic lymphedema by a sequenced and targeted treatment and management program based around a combination of Decongestive Lymphatic Therapy (DLT) with compression therapy, when the latter is desired as an adjunct to DLT. Treatment in the maintenance phase should include compression garments, self-management, including self massage, meticulous personal hygiene and skin care, in addition to lymphtransport promoting excercises and activities, and, if desired, pneumatic compression therapy applied in the home. When conservative treatment fails, or gives sub optimal outcomes, the management of primary lymphedema can be improved, where appropriate, with the proper addition of surgical interventions, either reconstructive or ablative. These two surgical therapies can be more effective when fully integrated with manual lymphatic drainage (MLD)-based DLT postoperatively. Compliance with a long-term commitment to MLD/DLT and particularly compression postoperatively is a critical factor in determining the success of any new treatment strategy involving either reconstructive or palliative surgery. The future of management of primary lymphedema has never been brighter with the new prospect of gene-and perhaps stem-cell oriented management. PMID- 24212290 TI - Is local stiffness, as measured by radio frequency, more sensitive than intima media thickness? AB - AIM: The aim of our study was to explore the changes in common carotid arterial intima-media thickness (CCA IMT) and local arterial stiffness to evaluate, non invasively, early vascular disease in patients with cardiovascular (CV) risk factors and "normal" carotid IMT (<0.9 mm). METHODS: We studied 50 patients (mean age 42 years+/-14), with no history of cardio-cerebrovascular events and "normal" IMT. We assessed the traditional cardiovascular risk factors, the CCA IMT, and the local stiffness with Quality Arterial Stiffness technology, based on Radio frequency signal (RFQAS-ESAOTE, Italy). CCA distensibility coefficient (DC), compliance coefficient (CC), pulse wave velocity (PWV) and beta parameter were measured in patients, with and without traditional cardiovascular risk factors. 25 subjects with risk factors (mean age 49+/-13) were compared with 25 controls (mean age 36+/-12). RESULTS: We did not find any significant differences in the IMT measurement between subjects with CV risk factors compared to controls (0.530+/-0.99 mm vs. 0.626+/-0.127 mm; P=5.68). The mean DC (0.030+/-0.014 1/kPa vs. 0.0221+/-0.016 1/kPa; P<0.05) and CC (1.087+/-0.47 mm2/kPA vs. 0.864+/-0.41 mm2/kPA; P<0.05), were significantly lower, while PWV (6.21+/-1.74 m/s vs. 7.68+/ 2.07 m/s; P<0.05) and beta (7.67+/-4.09 m/s vs. 10.45+/-5.58 m/s; P<0.05) were significantly higher in subjects with CV risk factors. ROC curves showed that PWV>6.05 m/s better identified, among patients with IMT <0.9 mm, those with cardiovascular risk factors (sensitivity 82.0% specificity 62.0%; AUC 0.73). CONCLUSION: Increased stiffness is a result of change both in quantity and quality of the arterial wall. Arterial functional changes and distention alterations may herald the onset of vascular disease before manifestation of symptoms or detection of preclinical atherosclerotic lesions. PMID- 24212291 TI - Endovascular treatment of descending thoracic aortic disease. A single center experience. AB - AIM: Aim of the study was to assess if endovascular treatment is a feasible alternative in patients with descending thoracic aortic disease. METHODS: Seventy three patients were admitted for stent-grafting of descending thoracic aortic disease during the period 1997-2008. The majority of the patients had aneurysm (35) or type B dissection (21), but also traumas, penetrating ulcers and other conditions were treated. Sixteen (22%) were unfit for open surgery. Thirty-four (47%) of the patients were symptomatic and 18 had rupture. The primary technical success rate was 96%. RESULTS: Early mortality (<30 days) for the whole group was 3%. Early endoleak (<30 days) was identified in 11 patients (15%) of whom 4 (5%) had a secondary procedure. In addition, two trauma patients required insertion of a new stent-graft due to stent-graft collapse. Two patients had stroke, one had paraplegia and two paraparesis. Mean follow-up was 3.1 years (range 0-12 years). Late endoleak (>30 days) was identified in 5 patients (7%) treated by 6 secondary procedures. One patient (1.7%) had an explant. Two patients have had extensions of endografts due to increasing diameter of the aorta at the distal end of the stent-graft. CONCLUSION: Endovascular treatment seems to be a viable alternative in patients with descending thoracic aortic disease. PMID- 24212292 TI - Prosthetic axillary-axillary arm loop arteriovenous graft for hemodialysis. AB - AIM: In this study we present our experience with an alternative technique of vascular access for hemodialysis in which a prosthetic graft was placed as subcutaneous arm loop and anastomosed to the axillary artery and vein. METHODS: Patients included in this study were those with end stage renal disease (ESRD) requiring hemodialysis access who did not have suitable vein to perform autogenous AVF in both upper limbs and Duplex examination revealed unsuitable brachial artery to perform prosthetic brachial-axillary access. RESULTS: Forty one patients with ESRD underwent axillary-axillary arm loop AVG for hemodialysis. The primary patency rate at 1 year was 63.4% and at 2 years was 21.8%. The secondary patency rate at 1 year was 75.6% and at 2 years was 43.5%. CONCLUSION: Axillary-axillary arm loop AVG provides an acceptable option of vascular access for hemodialysis which can be used to recruit all possible configurations in the upper limb before shifting to chest wall options. PMID- 24212293 TI - Socioeconomic deprivation does not affect prescribing of secondary prevention in patients with peripheral arterial disease. AB - AIM: Aim of the study was to assess the effect of socioeconomic deprivation on prescribing of cardiovascular secondary prevention medications in patients referred with peripheral arterial disease (PAD). METHODS: A retrospective review of vascular clinic referrals was performed. All patients referred from primary care with suspected PAD over a two month period were included. The deprivation score, prescription of cardiovascular secondary prevention medications, smoking status and the presence of cardiovascular co-morbidities (coronary artery or cerebrovascular disease--CAD/CVD) were assessed. Comparison was made between socioeconomic groups using the Carstairs Deprivation (DepCat) Score and between patients with and without a history of currently existing cardiovascular co morbidities. RESULTS: The study included 391 patients. Almost two thirds of patients (253) were from the most deprived socioeconomic groups and were significantly younger at presentation (median age DepCat 7: 63 yrs, DepCat 1-2: 74.5 yrs, P<0.0001). The majority of patients with a prior history of CAD/CVD were prescribed secondary preventative medications at the time of referral with suspected PAD whereas those with no prior history of CAD/CVD, (212 patients, 54%) were significantly less likely to be prescribed antiplatelets (47% vs. 83%), statins (45% vs. 86%) or ACEi/ARBs (29% vs. 68%) (all P<0.05). Secondary prevention prescribing did not differ between socioeconomic groups. CONCLUSION: Secondary prevention prescribing is inadequate in patients with suspected PAD regardless of socioeconomic group and is significantly lower in those without previously diagnosed CAD/CVD. There remains a lack of appreciation of the high cardiovascular risk associated with PAD. PMID- 24212294 TI - Association between serum levels of pro-metalloproteinase 1, tissue inhibitor of metalloproteinases 1 and 2 and prevalent cardiovascular disease in a population based study. AB - AIM: The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. METHODS: Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models. RESULTS: Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P(for trend)=0.006 and P=0.001, respectively) and inflammatory factors (P(for trend)=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (OR(adjusted)=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (OR(adjusted)=0.25; 95% CI=0.11 to 0.60; P(for trend)=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease. CONCLUSION: A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease. PMID- 24212295 TI - Carotid stenting may be safer than carotid endarterectomy in patients with contralateral carotid occlusion. PMID- 24212296 TI - Requirements for angiology/vascular medicine. PMID- 24212297 TI - Silyl-protected dioxaborinanes: application in the Suzuki cross-coupling reaction. AB - The synthesis of a range of novel silyl-protected dioxaborinanes as a column- and bench-stable boron reagent were found to be advantageous to achieving good yields in palladium-catalysed cross-coupling reactions under standard conditions. PMID- 24212298 TI - Lipoprotein lipase gene sequencing and plasma lipid profile. AB - Lipoprotein lipase (LPL) plays a crucial role in lipid metabolism by hydrolyzing triglyceride (TG)-rich particles and affecting HDL cholesterol (HDL-C) levels. In this study, the entire LPL gene plus flanking regions were resequenced in individuals with extreme HDL-C/TG levels (n = 95), selected from a population based sample of 623 US non-Hispanic White (NHW) individuals. A total of 176 sequencing variants were identified, including 28 novel variants. A subset of 64 variants [common tag single nucleotide polymorphisms (tagSNP) and selected rare variants] were genotyped in the total sample, followed by association analyses with major lipid traits. A gene-based association test including all genotyped variants revealed significant association with HDL-C (P = 0.024) and TG (P = 0.006). Our single-site analysis revealed seven independent signals (P < 0.05; r2 < 0.40) with either HDL-C or TG. The most significant association was for the SNP rs295 exerting opposite effects on TG and HDL-C levels with P values of 7.5.10-4 and 0.002, respectively. Our work highlights some common variants and haplotypes in LPL with significant associations with lipid traits; however, the analysis of rare variants using burden tests and SKAT-O method revealed negligible effects on lipid traits. Comprehensive resequencing of LPL in larger samples is warranted to further test the role of rare variants in affecting plasma lipid levels. PMID- 24212300 TI - Volume of milk obtained in relation to location and circumstances of expression in mothers of very low birth weight infants. AB - BACKGROUND: Given the importance of mother's milk for very low birth weight (VLBW) infants, it would be helpful to know which circumstances are most favorable for milk expression. OBJECTIVE: This study aimed to estimate the volume of milk obtained by mothers of VLBW infants as a function of proximity to the infant and use of the kangaroo position during the actual expression. METHODS: In this prospective cohort study, when the infant was stable and the mother had established a breastfeeding routine, she was given a notebook in which to record the location of expression and the amount of milk expressed for 10 consecutive days. Breast milk expression volumes were recorded and analyzed. RESULTS: Data were collected on 26 mother-VLBW infant dyads and 1642 milk expressions. The first early morning expressions (n = 276, 17%) were conducted at home. Thereafter, 743 (45%) expressions were conducted far from the infant, either in a different room within the hospital or at home, and 623 (38%) were performed in proximity to the infant (beside the incubator, during kangaroo mother care [KMC], after KMC, or during kangaroo father care). The mean milk volume was significantly higher when expression was conducted in proximity to the infant. When only milk expressions conducted in proximity to the infant were considered, volumes obtained during KMC (107.7 mL, 91.8-123.5) and after KMC (117.7 mL, 99.0 136.5) were significantly higher than those obtained beside the incubator (96.9 mL, 79.9-113.9), respectively, P = .0030 and P = .0024. CONCLUSION: Milk expression conducted in proximity to the infant, particularly during and immediately after KMC, is associated with higher milk volume. PMID- 24212299 TI - Whole body synthesis rates of DHA from alpha-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats. AB - Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from alpha-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain. PMID- 24212301 TI - One pot synthesis of bioactive benzopyranones through palladium-catalyzed C-H activation and CO insertion into 2-arylphenols. AB - Palladium-catalyzed oxidative carbonylation of 2-arylphenols through C-H bond activation and C-C and C-O bond formation under acid-base free and mild conditions has been developed. The reaction tolerates a variety of substrates and provides biologically important benzopyranone derivatives in up to 87% isolated yield. PMID- 24212302 TI - Ocular trauma, an evolving sub specialty. PMID- 24212303 TI - Pre-operative variables affecting final vision outcome with a critical review of ocular trauma classification for posterior open globe (zone III) injury. AB - PURPOSE: To identify pre-operative variables affecting the outcome of posterior open globe (zone III) injuries. Secondary objective was to re-look at the definition or landmarks for zone III injury and its clinical significance for predicting visual prognosis following open globe injury. MATERIALS AND METHODS: Retrospective review of medical records of all hospitalized patients with surgical repair of open globe injury over last 10 years at a tertiary referral eye care center in Singapore. Out of 172 eyes with open globe injury, 28 eyes (16.3%) with zone III injury was identified and reviewed further. Pre-operative visual acuity (VA) and other variables, extent of scleral wound in reference to rectus insertion, relative afferent pupillary defect (RAPD) and final vision outcome were recorded. RESULTS: Median age was 37 years with male predilection (92.9%). Mean follow-up was 12.9 months. Pre-operative VA was no light perception (NLP) in 16 (57.1%) eyes. Final VA remained NLP in 14 eyes (50.0%). The factors contributing to poor post-operative vision based on univariate regression analysis were the presence of RAPD, poor pre-operative VA, blunt trauma, extent of trauma, associated traumatic cataract, hyphema, vitreous loss and associated vitreo-retinal trauma. Further on, zone III injuries with scleral wound limited anterior to rectus insertion (6 eyes) had better vision outcome than those with injuries extending beyond rectus insertion (22 eyes). CONCLUSION: Initial VA, blunt ocular trauma, visual axis involvement, loss of light perception, presence of RAPD, traumatic cataract, hyphema, vitreous loss were the important determinants for final visual outcome in patients with zone III injury. Wound extending posterior to rectus insertion has poorer outcome as those limited anterior to rectus insertion. We suggest that there may be a need to relook at zone III injuries with reference to rectus insertion for prognostic significance, and further studies are warranted. PMID- 24212304 TI - Determinants of severity at presentation among young patients with early onset glaucoma. AB - AIM: The aim of this study was to evaluate the clinical, socio-economic, and demographic factors associated with the severity at presentation among juvenile primary open angle glaucoma (JOAG) patients. MATERIALS AND METHODS: Age at diagnosis, family history, baseline intraocular pressure (IOP), access to health care, socio-economic status, and glaucoma awareness among 80 unrelated JOAG patients presenting between 10 years and 40 years of age were analyzed for their association with the severity at presentation. Severity at presentation was graded based on worse eye visual field using the advanced glaucoma intervention study score and on binocular visual field defects at presentation. RESULTS: Patients with a positive family history presented 4 years earlier (P = 0.045, confidence interval [CI]: 0.09-8.8) compared to those without a family history. Lower socio-economic status (Odds ratio [OR] 5.7, P = 0.01, CI: 1.5-22), and higher baseline IOP (OR 7, P = 0.003, CI: 1.9-26) were associated with severe glaucomatous visual field defect at presentation. A negative family history was associated with a 10 times likelihood of presenting with a severe glaucomatous field defect (OR 0.1, P = 0.007, CI: 0-0.5). CONCLUSIONS: Clinical, socio economic, and demographic factors are contributory to the severity at presentation among young patients with early onset glaucoma. Presence of a family history is associated with an earlier presentation among these patients and a reduced risk of the severe presentation. PMID- 24212305 TI - The effects of renal transplantation on diabetic retinopathy: clinical course and visual outcomes. AB - PURPOSE: To elucidate the clinical course of diabetic retinopathy (DR) after renal transplantation (RT) in a hospital based cohort. DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 56 eyes of 28 patients, who had DR and end stage renal disease (ESRD) due to diabetes and had undergone RT, were included in this study. Diagnosis and management of DR was carried out according to early treatment of diabetic retinopathy study (ETDRS) guidelines. DR outcome was defined as worsening if there was >2 step increase in the grade of DR or need for intervention such as laser (macular or pan retinal) or vitreoretinal surgery, improvement for <2 step change while stabilization was defined if DR remained within these two limits. RESULTS: The mean age of the patients were 48.9 years. The mean duration of diabetes in the study group was 12.7 years. The patients were followed-up for a mean period of 52.2 +/- 43.6 months. The pre-transplant mean Best corrected visual acuity (BCVA) was 0.4876 log MAR units and post transplant mean BCVA was 0.4858 (P = 0.05). However, there was a significant visual improvement in first 20 months of renal transplant (P = 0.03). Worsening of DR was noted in 16 (32%) eyes whereas improvement was seen in 4 (8%). However, majority of eyes 30 (60%) had stable retinopathy at the final follow-up. CONCLUSIONS: RT stabilized the retinopathy status in the majority of patients although in a minor subset the disease course was unpredictable. PMID- 24212306 TI - A new Gujarati language logMAR visual acuity chart: development and validation. AB - AIMS: Gujarati is the main spoken language of a large proportion of the population of India. The aim of this study was to develop and validate a new Minimum Angle of Resolution (logMAR) visual acuity chart in the Gujarati language. MATERIALS AND METHODS: A new Gujarati visual acuity chart was designed to logMAR specifications using Gujarati optotypes experimentally selected to have similar relative letter legibility under spherical and cylindrical defocus. The chart validation study was carried out using 153 adult subjects in a large clinical setting in India. Subjects who were literate in English and Gujarati participated in the study. Visual acuity was measured with the new Gujarati logMAR chart and a modified Early Treatment of Diabetic Retinopathy Study-(m ETDRS) logMAR chart. The method of presentation was randomized between the charts. Repeat visual acuity was measured on a subsequent day with a second version of the Gujarati logMAR chart. RESULTS: The Gujarati chart correlated highly with the m-ETDRS logMAR chart (r2 = 0.974). The mean visual acuity difference (Gujarati - m-ETDRS logMAR) was equal to three letters (-0.06 logMAR). The Gujarati logMAR chart also proved to be highly repeatable (r2 = 0.994, test retest) with 95% CI of +/- 0.04 logMAR. CONCLUSIONS: The new Gujarati logMAR visual acuity chart provides a valid and repeatable tool for the measurement of visual acuity in native Gujarati language speakers. PMID- 24212307 TI - Evaluation of changes in retinal nerve fiber layer thickness and visual functions in cases of optic neuritis and multiple sclerosis. AB - CONTEXT: Retinal nerve fiber layer (RNFL) thinning has been demonstrated in cases of optic neuritis (ON) and multiple sclerosis (MS) in Caucasian eyes, but no definite RNFL loss pattern or association with visual functions is known in Indian eyes. AIM: To evaluate RNFL thickness in cases of ON and MS, and to correlate it with visual function changes in Indian patients. SETTINGS AND DESIGN: Cross-sectional case-control study at a tertiary level institution. MATERIALS AND METHODS: Cases consisted of patients of (i) typical ON without a recent episode (n = 30:39 ON eyes and 21 fellow eyes), (ii) MS without ON (n = 15;30 eyes) while the controls were age-matched (n = 15; 30 eyes). RNFL thickness was measured using the Stratus 3 degrees CT. The visual functions tested included the best-corrected visual acuity (BCVA), contrast sensitivity, stereopsis, visual evoked responses, and visual fields. STATISTICAL ANALYSIS USED: Intergroup analysis was done using ANOVA and Pearson's correlation coefficient used for associations. RESULTS: RNFL thickness was reduced significantly in the ON and MS patients compared to the controls (P-0.001). Maximum loss is in the temporal quadrant. Lower visual function scores are associated with reduced average overall RNFL thickness. In ON group, RNFL thinning is associated with severe visual field defects while contrast sensitivity has strongest correlation with RNFL in the MS group. CONCLUSIONS: RNFL thickness is reduced in ON and MS cases in a pattern similar to Caucasians and is associated with the magnitude of impairment of other visual parameters. Contrast sensitivity and stereoacuity are useful tests to identify subclinical optic nerve involvement in multiple sclerosis. PMID- 24212308 TI - Human intraretinal myelination: axon diameters and axon/myelin thickness ratios. AB - PURPOSE: Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons. MATERIALS AND METHODS: Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet. RESULTS: Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P <= 0.01). Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01). The relationship between axon diameter/fiber diameter (the G-ratio) seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01) in the retina but negatively correlated to axon diameter in the nerve (P < 0.001). CONCLUSION: Intraretinally myelinated axons are larger than non myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes. PMID- 24212309 TI - 20G silicone rod as monocanalicular stent in repair of canalicular lacerations: experience from a tertiary eye care centre. AB - To evaluate the outcome of 20G silicone rod as monocanalicular stent in canalicular lacerations. Retrospective case series involving patients between July 2006 and June 2010. Fourteen canalicular repairs in 12 consecutive patients were done in the study period. Eleven were male and mean age was 30.5 years. A single canaliculus was involved in 10 patients and associated injury to the globe was noted in 3 patients. The median lag time between injury and repair was 3 (range 1-9) days. The mean duration of stenting was 6.9 (SD 3.2) weeks. Spontaneous extrusion of monocanalicular stent occurred in 3 patients. Patency on syringing was noted in 10 (70%) canaliculi over a median follow up of 7 (range 2 17) months. 20G silicone rod may be used as an effective and economical alternative in canalicular lacration repairs. PMID- 24212310 TI - Pigmented paravenous chorioretinal atrophy with Coat's like response. AB - Pigmented paravenous chorioretinal atrophy (PPCRA) is an uncommon retinal disorder of unknown etiology that is neither well understood nor classified. We report an atypical case of PPCRA, associated with Coat's like response (CLR) in a 64-year-old man of Asian origin. Both the eyes were involved, though asymmetrically. PMID- 24212311 TI - Infestation of the lacrimal sac by Rhinosporidium seeberi: a clinicopathological case report. AB - Rhinosporidium seeberi , till recently known as a fungus, has been reclassified as a protistan parasite. It infects humans and many animal species. The authors describe a rare case of oculosporidiosis with involvement of the lacrimal sac exhibiting features of idiopathic orbital inflammatory disease in a young male patient. Clinical features, pathophysiology, and management of lacrimal sac rhinosporidiosis have been discussed. PMID- 24212312 TI - Infectious scleritis: clinical spectrum and management outcomes in India. AB - In this retrospective case series, we studied the predisposing factors, causative organisms, clinical spectrum, and outcomes of 12 cases of culture-proven infectious scleritis. Nine of 12 patients had a history of preceding trauma (surgical or accidental). Past surgical history included small-incision cataract surgery (4), pterygium surgery (1), and trabeculectomy (1). Six patients had multifocal scleral abscesses due to Pseudomonas, Klebsiella, or Nocardia. Only 2 patients retained useful vision (>6/18). A poor visual acuity at presentation usually resulted in a worse visual outcome (P = 0.005). Four eyes developed phthisis. The addition of surgical intervention did not result in a significantly better visual outcome than medical management alone (P = 0.209), but resulted in a higher globe preservation rate (P = 0.045). Therefore, we concluded that infection must be ruled out in cases of scleritis with preceding history of trauma, and aggressive surgical intervention improves the anatomical outcome but does not change the visual outcome. PMID- 24212313 TI - Congenital combined eyelid imbrication and floppy eyelid syndrome: case report and review of literature. AB - Congenital eyelid imbrication syndrome (CEIS) is an extremely rare, benign, transient, self-limiting eyelid malposition disorder. The classic triad of signs in patients with a CEIS consists of bilateral upper eyelids overriding the lower eyelids when child was in sleep, bilateral medial and lateral canthal tendon laxity and tarsal conjunctival hyperemia. We report a third case of congenital combined eyelid imbrication and floppy eyelid syndrome in healthy neonate that was resolved within a week with conservative treatment. PMID- 24212314 TI - Optical coherence tomographic findings in optic nerve hypoplasia. AB - We investigated a case of unilateral optic nerve hypoplasia using spectral domain optical coherence tomography (SDOCT). Optical coherence tomography was done on both eyes using 5-line Raster scan for the fovea to analyze the retinal nerve fiber layer thickness, inner retinal layer thickness, outer retinal layer thickness, and optic disc cube scan for the disc. Retinal nerve fiber layer thickness, inner retinal layer thickness, and outer retinal layer thickness were manually measured at 21-points of each five lines, and results were compared between both eyes. Retinal nerve fiber layer thickness and inner retinal layer thickness of optic nerve hypoplasia were significantly thinner than the opposite eye, but there was no significant difference in the thickness of the outer retinal layer between both eyes. PMID- 24212315 TI - Isolated abducens nerve palsy with hyperhomocysteinemia: association and outcomes. AB - Ischemic abducens nerve palsy usually presents as isolated cranial nerve palsy in the middle aged and elderly patients with known risk factors such as diabetes mellitus, hypertension, dyslipidemia, carotid artery disease, etc., In this report, we describe four patients with isolated abducens nerve palsy who presented with an acute onset diplopia whose detailed history and examination were suggestive of an ischemic etiology. Detailed systemic and laboratory evaluation revealed hyperhomocysteinemia as the only potential risk factor. To the best of our knowledge this is the first report of association of hyperhomocysteinemia and isolated abducens nerve palsy. PMID- 24212316 TI - Surgical outcomes of inverted internal limiting membrane flap technique for large macular hole. AB - We are presenting the initial results of inverted internal limiting membrane (ILM) flap technique for large macular hole. Five eyes of five patients with large diameter macular hole (>700 MUm) were selected. All patients underwent inverted ILM flap technique for macular hole. Anatomical closure and functional success were achieved in all patients. There was no loss of best-corrected visual acuity in any of the patients. Inverted ILM flap technique in macular hole surgery seems to have a better hole closure rates, especially in large diameter macular holes. Larger case series is required to assess the efficacy and safety of this technique. PMID- 24212317 TI - Clinical utility of 18 Fluorodeoxyglucose (FDG)-PET/CT scans in patients with suspect ocular tuberculosis. AB - Systemic imaging of patients with suspect ocular tuberculosis include chest X rays and computed tomography (CT) scans. Reports have suggested a role for 18 fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) scans. We report on the clinical utility of 18 FDG PET/CT in two patients. Case 1: A 38-year-old female patient presented with recurrent anterior uveitis. A 18 FDG-PET scan revealed metabolically active supraclavicular and chest lymph nodes. An aspiration cytology of the cervical lymph node revealed caseating granulomas suggestive of tuberculosis. Case 2: A 58-year-old female patient presented with recurrent anterior uveitis. A 18 FDG-PET scan revealed metabolically active lymph nodes in the neck. A biopsy of the cervical lymph node revealed epithelioid granulomas suggestive of tuberculosis. Both patients were started on standard antitubercular therapy with a subsequent marked reduction of activity. PET/CT scans may suggest the sites of safe high-yield biopsies. PMID- 24212319 TI - Severe visual loss following waterload for transabdominal ultrasound. PMID- 24212318 TI - Beyond photography: evaluation of the consumer digital camera to identify strabismus and anisometropia by analyzing the Bruckner's reflex. AB - Amblyopia screening is often either costly or laborious. We evaluated the Canon Powershot TX1 (CPTX1) digital camera as an efficient screener for amblyogenic risk factors (ARF). We included 138 subjects: 84-amblyopes and 54-normal. With the red-eye-reduction feature off, we obtained Bruckner reflex photographs of different sized crescents which suggested anisometropia, while asymmetrical brightness indicated strabismus; symmetry implied normalcy. Eight sets of randomly arranged 138 photographs were made. After training, 8 personnel, marked each as normal or abnormal. Of the 84 amblyopes, 42 were strabismus alone (SA), 36 had anisometropia alone (AA) while six were mixed amblyopes (MA). Overall mean sensitivity for amblyopes was 0.86 (95% CI: 0.83-0.89) and specificity 0.85 (95% CI: 0.77-0.93). Sub-group analyses on SA, AA and MA returned sensitivities of 0.86, 0.89 and 0.69, while specificities were 0.85 for all three. Overall Cohen's Kappa was 0.66 (95% CI: 0.62-0.71). The CPTX1 appears to be a feasible option to screen for ARF, although results need to be validated on appropriate age groups. PMID- 24212320 TI - Migraine is a marker for systemic disease. PMID- 24212321 TI - Comment on "Effect of dacryocystorhinostomy on systemic adverse effects of topical timolol maleate". PMID- 24212322 TI - Completion rates of anterior and posterior continuous curvilinear capsulorrhexis in pediatric cataract surgery for surgery performed by trainee surgeons with the use of a low-cost viscoelastic. PMID- 24212323 TI - Patients' actual care pathways often differ markedly from doctors' perceptions. PMID- 24212324 TI - Changing patterns in thyroid cancer incidence and mortality in the Slovak Republic by histological type and age. AB - BACKGROUND: Thyroid cancer (TC) is the most common malignant disease of the endocrine system; however, in the Slovak Republic (SR), time trends of incidence and mortality according to histological type and age of patients have never been reported. MATERIALS AND METHODS: Long-term (1968-2007) trends from the National Cancer Registry data of overall, histology and age-specific incidence and mortality in the SR have been calculated using join-point regression and other descriptive characteristics. RESULTS: Age-standardized overall incidence rates increased significantly in females by an estimated annual percentage change (APC) of 3.6 %, and in males by 2.2 %. Overall mortality decreased by APC -2.1 % in females and -0.9 % in males. The mean ages of female and male TC patients at the time of diagnosis significantly decreased; ages at the time of death significantly increased. The incidence of papillary carcinoma rose significantly in females by 8.9 %, compared with 6.1 % in males; follicular carcinoma in males and females was stable. Medullary carcinoma was stable in females; in males, it rose by 5.2 %. Poorly differentiated TC was stable in females; undifferentiated/anaplastic carcinomas decreased in both sexes. CONCLUSIONS: The incidence of TC, especially of selected histological types, is dramatically rising in the SR in both genders, while mortality is decreasing. Patients diagnosed in recent years are younger and died at a greater age than those reported in older national data. These trends seem to be affected by more intensive diagnosis in the most recent years. PMID- 24212325 TI - Non-therapeutic male circumcision performed on immigrant children from Africa in Spain. AB - OBJECTIVES: To study the frequency, characteristics, and complications of non therapeutic male circumcision on immigrant children from Africa in Spain. METHODS: This descriptive study focused on primary care consultations conducted at 21 Aragon health centres during 2010 and 2011. The data were gathered through interviewer-administered questionnaires to the parents of African children. Sociodemographic variables were studied, along with others related to the practice of circumcision. RESULTS: 283 questionnaires were obtained. 98.93 % of the children had undergone or were planning to undergo circumcision. 68.2 % were circumcised. Circumcisions were most frequently performed during a vacation to the country of origin (67.04 %), especially so for the Maghreb population. The remaining circumcisions had been performed in Spain. Half of the circumcisions practiced in Spain were performed at home, and 84 % of these were performed on Gambian children. CONCLUSIONS: The current study demonstrates that, in Aragon, Spain, almost all immigrant children from Africa have been or will be circumcised and that a considerable proportion has been circumcised at home by unqualified individuals. Gambians are particularly at risk of performing unsafe circumcision. PMID- 24212326 TI - Exploring subgroup effects by socioeconomic position of three effective school based dietary interventions: the European TEENAGE project. AB - OBJECTIVES: The aim of this study was to explore subgroup effects by high and low socioeconomic position (SEP) of three previously conducted, effective European interventions. METHODS: Reanalyses stratified by SEP were conducted by the research groups of each study. All studies were school-based: two multi-component interventions targeting intake of fat or fruit and vegetables (FV), and a free breakfast initiative. RESULTS: Computer-tailored advice affected fat intake among low, but not high SEP girls after 1 year. A multi-component intervention affected the total FV intake in both SEP groups, vegetable intake in low SEP and fruit intake in high SEP across three countries after 1 year, whereas free fruit affected total FV and fruit intake equally in both SEP groups in one country after 2 years. Providing a free healthy breakfast increased consumption of healthy food items only in the low SEP group. CONCLUSIONS: Reanalysing intervention studies by SEP is a quick and easy way to explore patterns in effects by SEP across interventions. Providing healthy food might be a promising strategy for decreasing social inequalities. PMID- 24212327 TI - A community-based study of early childhood sensory stimulation in home environment associated with growth and psychomotor development in Pakistan. AB - OBJECTIVES: Sensory stimulation (SS) is a non-nutritional modifiable risk factor for early childhood development. We assessed SS in home environment and examined its influence on physical growth and psychomotor development (PD). METHODS: A cross-sectional study was conducted in 26 communities in Pakistan among children aged <3 (n = 1,219). They were assessed at home visits using (1) Bayley's Infant Developmental Scale for PD, (2) home observation for measurement of the environment inventory for SS, (3) anthropometry and (4) socio-economic questionnaire. RESULTS: In rural homes, SS provided was lower as compared to urban counterparts (Adj mean diff: 4.47, 95 % CI 3.78, 5.16) and showed an association with stunting (Adj mean diff: -1.30, 95 % CI -1.93, -0.66), and underweight (Adj mean diff: -1.04, 95 % CI -1.71, -0.38) not explained by type of neighbourhood or socio-economic status. SS was associated with PD more than combined contribution of socio-economic status and rural-urban factors (Adj mean diff: 0.47, 95 % CI 0.30, 0.63). CONCLUSIONS: SS in rural homes may be a significant factor influencing the child development. There is a need to corroborate these results by additional research for integration in health policy initiatives. PMID- 24212328 TI - A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. AB - Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping. PMID- 24212329 TI - Dendrimer-mediated hydrothermal synthesis of ultrathin gold nanowires. AB - We report the use of poly(amidoamine) dendrimers as stabilizers to synthesize ultrathin Au nanowires (NWs) with a diameter of 1.3 nm via a hydrothermal approach. The formation of uniform Au NWs was optimized by varying the Au/Ag salt molar ratio, dendrimer stabilizers, and reaction solvent, temperature, and time. A novel growth mechanism involving a synergic facet-dependent deposition/reduction of Ag(I) and oriented migration of Au atoms is proposed based on density functional theory calculations and the experimental results. This work can significantly expand the scope of dendrimers as stabilizers to generate metal NWs in aqueous solution that may be further functionalized for different applications. PMID- 24212330 TI - Cancer-associated fibroblasts enhance the migration ability of ovarian cancer cells by increasing EZH2 expression. AB - The tumor microenvironment is thought to affect malignant transformation and tumor progression. The histone methyltransferase, enhancer of zeste homologue 2 (EZH2), has recently been suggested to play a critical role in the tumorigenesis of several types of human cancer. The aim of this study was to investigate the effects of cancer-associated fibroblasts (CAFs) on the expression of EZH2 and the migration ability of ovarian cancer cells, in order to explore the link between the tumor microenvironment and epigenetic regulation. The ovarian cancer cell lines, A2780, SKOV3 and ES2, were indirectly co-cultured with primary ovarian CAFs or normal fibroblasts (NFs). The migration ability of the ovarian cancer cells was determined by Transwell migration assay. The expression levels of EZH2 were assessed by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. The A2780-shEZH2 cells (A2780 cells transfected with shRNA targeting EZH2) were indirectly co-cultured with CAFs or NFs, and the changes in the expression levels of EZH2 and the migration ability of the cells were detected. The migration ability of the A2780, SKOV3 and ES2 cells co-cultured with CAFs was significantly enhanced (P<0.05) compared with the NF group and the cells cultured alone. The expression of EZH2 in the A2780, SKOV3 and ES2 cells was significantly increased following co-culture with CAFs (P<0.001) compared with the cells cultured alone but not those cultured with NFs. The migration ability of the A2780-shEZH2 cells was not significantly increased following co culture with CAFs (P>0.05). Our data indicate that CAFs enhance the migration ability of ovarian cancer cells partly by increasing EZH2 expression. PMID- 24212331 TI - Modern endovascular treatments of occlusive pediatric acute ischemic strokes: case series and review of the literature. AB - PURPOSE: Literature on the endovascular treatment of occlusive acute ischemic stroke (AIS) in the pediatric population remains nebulous. Clinical trials evaluating the role of systemic and intra-arterial thrombolysis, and mechanical thrombectomy have been strictly isolated to the adult population and largely unknown in their safety and efficacy in the pediatric group. METHODS: The authors present a review of the literature and their own two cases of occlusive acute ischemic stroke in children younger than the age of 10 years who were treated with modern endovascular devices, specifically with stent retrievers, and discuss their clinical and technical considerations as well as their limitations. RESULTS: In both pediatric patients, a combination of stent retriever and Penumbra aspiration were used to achieve Thrombolysis In Cerebral Infarction (TICI) 2a or greater with reduction of overall stroke burden. A reduction of National Institutes of Health Stroke Scale (NIHSS) of 8 or greater was achieved at discharge. At 3-month follow-up, the patients had a NIHSS of 6 and 2, respectively. One patient continued to improve from NIHSS of 6 to 3 at 6 months. CONCLUSION: In carefully, selected pediatric patients, modern endovascular techniques may be used to treat occlusive pediatric AIS. However, larger clinical trials are needed to evaluate the overall safety and effectiveness. PMID- 24212332 TI - Tidal volume and airway pressure under percutaneous transtracheal ventilation without a jet ventilator: comparison of high-flow oxygen ventilation and manual ventilation in complete and incomplete upper airway obstruction models. AB - PURPOSE: Percutaneous transtracheal ventilation (PTV) can be life-saving in a cannot ventilate, cannot intubate situation. The aim of this study was to investigate the efficacy of PTV by measuring tidal volumes (VTs) and airway pressure (Paw) in high-flow oxygen ventilation and manual ventilation using a model lung. METHODS: We examined 14G, 16G, 18G, and 20G intravenous catheters and minitracheotomy catheters. In high-flow oxygen ventilation, the flow was set to 10 L/min, while the inspiratory:expiratory phases (I:E) were 1 s:4 s in the complete upper airway obstruction model and 1 s:1 s in the incomplete obstruction model. In manual ventilation, I:E were 2 s:4 s in the complete obstruction model and 2 s:3 s in the incomplete obstruction model. We ventilated through each catheter for 2 min and measured VT and Paw. RESULTS: In high-flow ventilation, the average VTs were approximately 150 ml and <100 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. The VTs obtained were reduced when the bore size was decreased. In manual ventilation, the average VTs were over 300 ml and approximately 260 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. In high-flow ventilation, the airway pressure tended to be higher. The minitracheotomy catheters produced over 800 ml of VT and created almost no positive end-expiratory pressure. CONCLUSIONS: High-flow ventilation tends to result in higher airway pressure despite a smaller VT, which is probably due to a PEEP effect caused by high flow. PMID- 24212334 TI - Synthesis, structure and spectroscopic analyses of aquachloridooxidodiperoxidomolybdate(VI). AB - A novel aquachloridooxidodiperoxidomolybdate(vi), [MoClO(O2)2(OH2)](-), was crystallised as tetraethylammonium and triethylmethylammonium salts from strongly acidic aqueous solutions, and was structurally analysed by single crystal X-ray diffraction and NMR spectroscopy. The aqueous behaviour of the present anion observed by (17)O NMR agrees with that reported in a previous speciation study. PMID- 24212333 TI - Computed tomography angiography intraluminal filling defect is predictive of internal carotid artery free-floating thrombus. AB - INTRODUCTION: Filling defects at the internal carotid artery (ICA) origin in the work-up of stroke or transient ischemic attack may be an ulcerated plaque or free floating thrombus (FFT). This may be challenging to distinguish, as they can appear morphologically similar. This is an important distinction as FFT can potentially embolize distally, and its management differs. We describe a series of patients with suspected FFT and evaluate its imaging appearance, clinical features, and evolution with therapy. METHODS: Between 2008 and 2013, we prospectively collected consecutive patients with proximal ICA filling defects in the axial plane surrounded by contrast on CT/MR angiography. We defined FFT as a filling defect that resolved on follow-up imaging. We assessed the cranial-caudal dimension of the filling defect and receiver operating characteristics to identify clinical and radiological variables that distinguished FFT from complex ulcerated plaque. RESULTS: Intraluminal filling defects were identified in 32 patients. Filling defects and resolved or decreased in 25 patients (78 %) and felt to be FFT; there was no change in 7 (22 %). Resolved defects and those that decreased in size extended more cranially than those that remained unchanged: 7.3 mm (4.2-15.9) versus 3.1 mm (2.7-3.7; p = 0.0038). Receiver operating characteristic analysis established a threshold of 3.8 mm (filling defect length), sensitivity of 88 %, specificity of 86 %, and area under the curve of 0.86 (p < 0.0001) for distinguishing FFT from plaque. CONCLUSION: Filling defects in the proximal ICA extending cranially >3.8 mm were more likely to be FFT than complex ulcerated plaque. Further studies evaluating filling defect length as a predictor for FFT are warranted. PMID- 24212335 TI - Evolution of the hemagglutinin gene of the influenza A(H1N1)pdm09 virus in Morocco during two influenza seasons 2009-2011. AB - To study genetic evolution of Moroccan influenza A(H1N1)pdm09 virus strains, we conducted a molecular characterization of the hemagglutinin gene subunit 1 (HA1) of 36 influenza A(H1N1)pdm09 virus strains. The stains were collected from patients in Rabat and Casablanca during two influenza seasons 2009-2010 and 2010 2011. Nucleotide and amino acid sequences of 14 influenza A(H1N1)pdm09 virus strains from 2009 to 2010 were ~97 and 99 %, respectively, similar to the reference strain A/California/07/2009 (H1N1). Phylogenetic analysis of 22 influenza A(H1N1)pdm09 virus strains from 2010 to 2011 revealed a co-circulation of three well-described different genetic groups. Most important, none of the identified groups showed significant changes at the antigenic site of the virus HA1 subunit which may alter the efficacy of California/07/2009 (H1N1) vaccine. PMID- 24212336 TI - The ethylene-inhibitor aminoethoxyvinylglycine restores normal nodulation by Rhizobium leguminosarum biovar. viciae on Vicia sativa subsp. nigra by suppressing the 'Thick and short roots' phenotype. AB - Nodulation of Vicia sativa subsp. nigra L. by Rhizobium bacteria is coupled to the development of thick and short roots (Tsr). This root phenotype as well as root-hair induction (Hai) and root-hair deformation (Had) are caused by a factor(s) produced by the bacteria in response to plant flavonoids. When very low inoculum concentrations (0.5-5 bacteria.ml(-1)) were used, V. sativa plants did not develop the Tsr phenotype and became nodulated earlier than plants with Tsr roots. Furthermore, the nodules of these plants were located on the primary root in contrast to nodules on Tsr roots, which were all located at sites of lateral root emergence. The average numbers of nodules per plant were not significantly different for these two types of nodulation. Root-growth inhibition and Hai, but not Had, could be mimicked by ethephon, and inhibited by aminoethoxyvinylglycine (AVG). Addition of AVG to co-cultures of Vicia sativa and the standard inoculum concentration of 5.10(5) bacteria.ml(-1) suppressed the development of the Tsr phenotype and restored nodulation to the pattern that was observed with very low concentrations of bacteria (0.5-5 bacteria.ml(-1)). The delay in nodulation on Tsr roots appeared to be caused by the fact that nodule meristems did not develop on the primary root, but only on the emerging laterals. The relationship between Tsr, Hai, Had, and nodulation is discussed. PMID- 24212337 TI - Ultrastructural detection of ribulose-1,5-bisphosphate carboxylase protein and its subunit mRNAs in wild-type and holoenzyme-deficient Nicotiana using immuno gold and in-situ-hybridization techniques. AB - In-situ-localization techniques have been adapted to the ultrastructural detection of the holoenzyme ribulose-1,5-bisphosphate carboxylase (RuBPCase) and its composite large- and smallsubunit mRNAs in wild-type and mutant RuBPCase deficient plantlets of Nicotiana tabacum L. Immuno-gold techniques which show the distribution of target proteins have confirmed visually the presence of the holoenzyme in the wild-type plastids and its total absence in the enzyme-less mutant. Using in-situ hybridization coupled with electron microscopy and biotinylated probes for the two subunits, we have directly visualized specific small-subunit mRNAs located in the cytoplasm and large-subunit mRNAs confined to plastids in the enzyme-deficient mutant, and with apparent distributions comparable to those visualized in the wild-type counterpart. These results show that (i) gene products can be visualized in situ by electronmicroscopy techniques under conditions where the respective cellular compartments are readily recognizable and (ii) that an accumulation of mRNAs corresponding to the composite subunits can occur without translation and-or assembly of the protein. PMID- 24212338 TI - Vanadate mimics effects of fungal cell wall in eliciting gene activation in plant cell cultures. AB - Cell-suspension cultures of peanut (Arachis hypogaea L.) can be used as a very sensitive and rapidly responding physiological system for monitoring extracellular signals. Elicitors effect the activation of the genes that code for a set of enzymes synthesizing stilbenes. Within 2-6 h after administering micromolar, concentrations of orthovanadate to the suspended cells, the enzyme activities of phenylalanine ammonia-lyase, stilbene synthase, and cinnamate 4 hydroxylase increased 10-to 100-fold. The transient time course of induction, and the quality and quantity of gene expression found with vanadate as artificial elicitor were very similar to those observed after biotic stress generated by fungal cell walls. The dose-response of vanadate as an elicitor of gene expression in intact cells matched precisely its inhibitory effect on the ATPase activity of isolated plasma membrane. By concentrating, on the profiles of cinnamate 4-hydroxylase activity, we observed differences between the effects elicited by fungal cell wall or vanadate when different stages of cell development were analyzed. Unlike the fungal elicitor, vanadate did not induce the hydroxylase activity when cells at the stationary phase of the cell cycle were used. This lack of response was not the result of a decrease in membrane biosynthesis. The finding, that the effects of vanadate and fungal elicitor are additive indicates that vanadate does not interfere negatively with the perception of the biotic signal but rather addresses the same intracellular intermediate of the signalling process. We hypothesize that membrane potentials created or modulated by ATPases may be intermediates in the signal chain, starting with the recognition process at the plasma membrane and eventually leading to the production of stilbenes as low-molecular-weight plant-defence products. PMID- 24212339 TI - Characterization of the isolated calcium-binding vesicles from the green alga Mougeotia scalaris, and their relevance to chloroplast movement. AB - The calcium-binding vesicles from the green alga Mougeotia scalaris were isolated and characterized after staining in vivo by neutral red or rhodamine B. They were found to possess, a protonated group with a pKa-9.9, typifying phenolic hydroxyl groups; upon titration, both, phenolic compound(s) and vital dye were concomitantly released from the vesicular matrix. A shift in peak absorbance from 450 nm to 540 nm of the vitally stained vesicles indicated that the neutral form of neutral red was bound to the vesicular, matrix as an intermediate form, stabilized via intermolecular hydrogen bonds to the phenolic compound(s). Up to 8.5.10(9) dye molecules were calculated to be adsorbed to a mean-size vesicle. Analysis of Langmuir adsorption isotherms, indicated that there were two binding sites each for both neutral red and rhodamine B. The isolated vesicles were devoid of calcium, probably because vesicular calcium, bound to the vesicle matrix, was displaced upon dye binding. Dye adsorption to the vesicles in vivo results in substantial inhibition of the reorientational movement of the Mougeotia chloroplast and is explained by dye-mediated disorder of the cellular calcium homoeostasis. PMID- 24212340 TI - Is a decreased water potential after withholding oxygen to roots the cause of the decline of leaf-elongation rates in Zea mays L. and Phaseolus vulgaris L.? AB - Leaf-elongation rates of Zea mays L. and Phaseolus vulgaris L. were measured in plants grown for 4 d in nutrient solution bubbled with N2 and in soil-grown waterlogged Phaseolus plants. Leaf water potential in both species was lower 3-4h after replacing aeration by N2-bubbling. In Zea, the water potential after 24 h or more was the same in control plants and plants with N2 treatment. In Phaseolus, the water potential of inundated plants and plants with N2 treatment was always lower than those of control plants. The leaf-elongation rate of both species was always lower in plants treated with N2, especially during light periods. In Zea, the elongation rate was lowest in the first 24 h, whilst in Phaseolus it was lowest on the last (fourth) day of treatment. There was no difference between N2 treatment and inundation experiments. It is concluded that during the first hours of treatment the leaf-elongation rate was reduced as a consequence of the lower water potential. Thereafter, however, elongation rates were lower than could be expected on the basis of the plant's water relations. PMID- 24212341 TI - Gravitropism in a starchless mutant of Arabidopsis : Implications for the starch statolith theory of gravity sensing. AB - The starch-statolith theory of gravity reception has been tested with a mutant of Arabidopsis thaliana (L.) Heynh. which, lacking plastid phosphoglucomutase (EC 2.7.5.1) activity, does not synthesize starch. The hypocotyls and seedling roots of the mutant were examined by light and electron microscopy to confirm that they did not contain starch. In upright wild-type (WT) seedlings, starch-filled plastids in the starch sheath of the hypocotyl and in three of the five columellar layers of the root cap were piled on the cell floors, and sedimented to the ceilings when the plants were inverted. However, starchless plastids of the mutant were not significantly sedimented in these cells in either upright or inverted seedlings. Gravitropism of light-grown seedling roots was vigorous: e.g., 10(o) curvature developed in mutants rotated on a clinostat following a 5 min induction at 1 . g, compared with 14(o) in the WT. Curvatures induced during intervals from 2.5 to 30 min were 70% as great in the mutant as the WT. Thus under these conditions the presence of starch and the sedimentation of plastids are unnecessary for reception of gravity by Arabidopsis roots. Gravitropism by hypocotyls of light-grown seedlings was less vigorous than that by roots, but the mutant hypocotyls exhibited an average of 70-80% as much curvature as the WT. Roots and hypocotyls of etiolated seedlings and flower stalks of mature plants were also gravitropic, although in these cases the mutant was generally less closely comparable to the WT. Thus, starch is also unnecessary for gravity reception in these tissues. PMID- 24212342 TI - Amyloplasts are necessary for full gravitropic sensitivity in roots of Arabidopsis thaliana. AB - The observation that a starchless mutant (TC7) of Arabidopsis thaliana (L.) Heynh. is gravitropic (T. Caspar and B.G. Pickard, 1989, Planta 177, 185-197) raises questions about the hypothesis that starch and amyloplasts play a role in gravity perception. We compared the kinetics of gravitropism in this starchless mutant and the wild-type (WT). Wild-type roots are more responsive to gravity than TC7 roots as judged by several parameters: (1) Vertically grown TC7 roots were not as oriented with respect to the gravity vector as WT roots. (2) In the time course of curvature after gravistimulation, curvature in TC7 roots was delayed and reduced compared to WT roots. (3) TC7 roots curved less than WT roots following a single, short (induction) period of gravistimulation, and WT, but not TC7, roots curved in response to a 1-min period of horizontal exposure. (4) Wild type roots curved much more than TC7 roots in response to intermittent stimulation (repeated short periods of horizontal exposure); WT roots curved in response to 10 s of stimulation or less, but TC7 roots required 2 min of stimulation to produce a curvature. The growth rates were equal for both genotypes. We conclude that WT roots are more sensitive to gravity than TC7 roots. Starch is not required for gravity perception in TC7 roots, but is necessary for full sensitivity; thus it is likely that amyloplasts function as statoliths in WT Arabidopsis roots. Furthermore, since centrifugation studies using low gravitational forces indicated that starchless plastids are relatively dense and are the most movable component in TC7 columella cells, the starchless plastids may also function as statoliths. PMID- 24212343 TI - Separating the contribution of the upper and lower mesophyll to photosynthesis in Zea mays L. leaves. AB - The appearance of transverse sections of maize leaves indicates the existence of two airspace systems serving the mesophyll, one connected to the stomata of the upper epidermis and the other to the stomata of the lower surface, with few or no connections between the two. This study tests the hypothesis that the air-space systems of the upper and lower mesophyll are separated by a defined barrier of measurable conductance. A mathematical procedure, based on this hypothesis, is developed for the quantitative separation of the contributions made by the upper and lower halves of the mesophyll to carbon assimilation using gasexchange data. Serial paradermal sections and three-dimensional scanning-electron-microscope images confirmed the hypothesis that there were few connections between the two air-systems. Simultaneous measurements of nitrous-oxide diffusion across the leaf and of transpiration from the two surfaces showed that the internal conductance was about 15% of the maximum observed stomatal conductance. This demonstrates that the poor air-space connections, indicated by microscopy, represent a substantial barrier to gas diffusion. By measuring the CO2 and water-vapour fluxes from each surface independently, the intercellular CO2 concentration (c i) of each internal air-space system was determined and the flux between them calculated. This allowed correction of the apparent CO2 uptake at each surface to derive the true CO2 uptake by the mesophyll cells of the upper and lower halves of the leaf. This approach was used to analyse the contribution of the upper and lower mesophyll to CO2 uptake by the leaf as a whole in response to varying light levels incident on the upper leaf surface. This showed that the upper mesophyll was light-saturated by a photon flux of approx. 1000 MUmol.m(-2).s(-1) (i.e. about one-half of full sunlight). The lower mesophyll was not fully saturated by photon fluxes of nearly double full sunlight. At low photon fluxes the c i of the upper mesophyll was significantly less than that of the lower mesophyll, generating a significant upward flux of CO2. At light levels equivalent to full sunlight, and above, c i did not differ significantly between the two air space systems. The physiological importance of the separation of the air-space systems of the upper and lower mesophyll to gas exchange is discussed. PMID- 24212344 TI - Response of photosynthesis and respiration of resurrection plants to desiccation and rehydration. AB - Using non-invasive techniques (CO2 gas exchange, light scattering, light absorption, chlorophyll fluorescence, chlorophyll luminescence), we have analysed the response of respiration and photosynthesis to dehydration and rehydration of leaves of the resurrection plants Craterostigma plantagineum Hochst., Ramonda mykoni Reichb. and Ceterach officinarum Lam. et DC. and of the drought-sensitive mesophyte spinach (Spinacia oleracea L.). The following observations were made: (i) The rate of water loss during wilting of detached leaves of drought-tolerant resurrection plants was similar to that for leaves of the sensitive mesophyte, spinach. Leaves of Mediterranean xerophytes lost water much more slowly. (ii) Below a residual water content of about 20%, leaves of spinach did not recover turgor on rewatering, whereas leaves of the resurrection plants did. (iii) Respiration was less sensitive to the loss of water during wilting in the resurrection plants than in spinach. (iv) The sensitivity of photosynthesis to dehydration was similar in spinach and the resurrection plants. Up to a water loss of 50% from the leaves, photosynthesis was limited by stomatal closure, not by inhibition of reactions of the photosynthetic apparatus. Photosynthesis was inhibited and stomates reopened when loss of water became excessive. (v) After the leaves had lost 80% of their water or more, the light-dependent reactions of photosynthetic membranes were further inhibited by rewatering in spinach; they recovered in the resurrection plants. (vi) In desiccated leaves of the resurrection plants, slow rehydration reactivated mitochondrial gas exchange faster than photosynthetic membrane reactions. Photosynthetic carbon assimilation recovered only slowly. PMID- 24212345 TI - A stable blue-light-derived signal modulates ultraviolet-light-induced activation of the chalcone-synthase gene in cultured parsley cells. AB - Run-off transcription assays were used to demonstrate that both the ultraviolet (UV)-B and blue-light receptors control transcription rates for chalcone-synthase mRNA in the course of light-induced flavonoid synthesis in parsley (Petroselinum crispum Miller (A.W. Hill)) cell-suspension cultures. Blue and red light alone, presumably acting via a blue-light receptor and active phytochrome (far-red absorbing form) respectively, can induce accumulation of chalcone-synthase mRNA. The extent of the response is however considerably smaller than that obtained when these wavebands are applied in combination with UV light. A preirradiation with blue light strongly increases the response to a subsequent UV pulse and this modulating effect of blue light is stable for at least 20 h. The modulating effect is abolished by a UV induction but can be reestablished by a second irradiation with blue light. PMID- 24212346 TI - Sucrose uptake and partitioning in discs derived from source versus sink potato tubers. AB - The uptake of sucrose into isolated discs cut from sink (growing) and source (sprouting) potato (Solanum tuberosum L.) tuber tissue was studied. The uptake of sucrose into sink-tuber discs demonstrated biphasic kinetics. The large saturable component was inhibited by incubation of the discs with p-chloromercuribenzene sulfonic acid (PCMBS) whilst both the saturable and linear components were inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP). By contrast, in source-tuber discs, the linear component represented the majority of sucrose taken up, the saturable component playing only a minor role. In source discs, only the saturable component of uptake was inhibited by either PCMBS or CCCP. A large proportion (up to 25%) of sucrose taken up into sink-tuber discs was converted to starch but as the tubers aged the proportion of sucrose converted to starch decreased to the level found in source-tuber discs (approx. 3%). By contrast with sink-tuber discs (see Oparka and Wright, 1988b, Planta 175, 520 526) sucrose uptake into source discs was insensitive to turgor and demonstrated an uptake pattern similar to that of CCCP-treated sink tissue. It is proposed that exogenous sucrose is taken into the storage parenchyma of sink-tuber discs by both a carrier-mediated and a diffusional process. By contrast, uptake into the storage parenchyma of source-tuber discs appears to be essentially diffusional. The turgor sensitivity of sucrose uptake into sink-tissue discs may be mediated via the plasmalemma H(+)-ATPase. As the tuber ages the sucrose-uptake activity decreases and the capacity of the storage parenchyma to synthesise starch is lost. The data are discussed in relation to the in-vivo mechanisms of sucrose transport in storage tissues. PMID- 24212348 TI - Phosphoribosyl pyrophosphate and the measurement on inorganic pyrophosphate in plant tissues. AB - This work provides further evidence that plants contain appreciable amounts of inorganic pyrophosphate (PPi), and that breakdown of phosphoribosyl pyrophosphate (PPRibP) does not contribute significantly to the PPi detected in plant extracts. Inorganic pyrophosphate in extracts of the roots of Pisum sativum L., clubs of the spadices of Arum maculatum L., and the developing endosperm of Zea mays L. was assayed with pyrophosphate fructose 6-phosphate 1-phosphotransferase (EC 2.7.1.90), and with sulphate adenyltransferase (EC 2.7.7.4). The two different assays gave the same value for PPi content, and for recovery of added PPi. It was shown that PPRibP is converted to PPi during the extraction of PPi. However, the amounts of PPRibP in clubs of A. maculatum and the developing endosperm of Z. mays were negligible in comparison with the contents of PPi. PMID- 24212347 TI - Microtubule-binding proteins from carrot : I. Initial characterization and microtubule bundling. AB - Microtubules (MTs) participate in several processes of fundamental importance to growth and development in higher plants, yet little is known about the proteins with which they associate. Information about these molecules is important because they probably play a role in mediating functional and structural differences between various MT arrays. As a first step in gaining insight into this problem, we have isolated, from suspension-cultured cells of carrot (Daucus carota L.), non-tubulin proteins which bind to and affect microtubules (MTs) in vitro. These proteins were isolated using taxol-stabilized neuronal MTs as an affinity substrate. They cause MT bundling at substoichiometric concentrations, support the assembly of tubulin in vitro, and at low concentrations, decorate single MTs in a periodic fashion. The bundled MTs formed in vitro share similarities with those seen in situ in a variety of plant cells, including a center-center spacing of 34 nm, cold stability, resistance to anti-microtubule drugs, and sensitivity to calcium. The bundling activity is specific; other cationic proteins, as well as poly-L-lysine, do not behave in a similar manner. The bundling activity is insensitive to ATP. By assaying bundling activity with dark-field microscopy and employing standard biochemical procedures, a small number of polypeptides involved in the bundling process were identified. Affinity-isolated antibodies to one of these polypeptides (Mr=76000) were found to co-localize with MTs in the cortical array of protoplasts. Our findings are discussed with reference to the importance of these proteins in the cell and to their relationship to microtubule associated proteins in other eukaryotes. PMID- 24212349 TI - Leaf senescence in a non-yellowing mutant of Festuca pratensis: Proteins of photosystem II. AB - The senescence of leaves is characterized by yellowing as chlorophyll pigments are degraded. Proteins of the chloroplasts also decline during this phase of development. There exists a non-yellowing mutant genotype of Festuca pratensis Huds. which does not suffer a loss of chlorophyll during senescence. The fate of chloroplast membrane proteins was studied in mutant and wild-type plants by immune blotting and immuno-electron microscopy. Intrinsic proteins of photosystem II, exemplified by the light-harvesting chlorophyll a/b-binding protein (LHCP-2) and D1, were shown to be unusually stable in the mutant during senescence, whereas the extrinsic 33-kilodalton protein of the oxygen-evolving complex was equally lable in both genotypes. An ultrastructural study revealed that while the intrinsic proteins remained in the internal membranes of the chloroplasts, they ceased to display the heterogenous lateral distribution within the lamellae which was characteristic of nonsenescent chloroplasts. These observations are discussed in the light of possible mechanisms of protein turnover in chloroplasts. PMID- 24212350 TI - Reorganization of the endoplasmic reticulum in epidermal cells of onion bulb scales after cold stress: Involvement of cytoskeletal elements. AB - In the epidermal cells of onion (Allium cepa L.) bulb scales the endoplasmic reticulum (ER) can be subdivided into three domains: a peripheral tubular network, cisternae, and long tubular strands. The latter are the form in which the ER is moved in onion cells. During cold treatment the arrangement of the three domains changes drastically. The cisternae and long tubular strands disintegrate into short ER tubules which show rapid agitational motion. Long distance movement is inhibited. The peripheral tubular ER network is presumably retained during cold treatment. Rewarming of previously chilled bulb scales initiates the reorganization of the ER into the three domains. The ER is partly relocated during recovery from cold treatment. Redistribution and reorganization of the ER is not affected by the microtubule-destabilizing herbicides oryzalin and trifluralin (5 MUM). Cytochalasin D (2MUM), however, inhibits not only the relocation of ER material, as is evident by the absence of long tubular ER strands, but also the movement of other cell organelles. The latter cluster on top of the cisternae in a manner which is characteristic of treatment with the actin-filament inhibitor. The array of actin filaments is similar in unstressed, cold-treated cells, and cells which recover from low temperatures in the presence of oryzalin or tap water alone. In the presence of cytochalasin D the actin filaments are severely fragmented. The results indicate that low temperatures most likely influence either the interaction of the force-generating system, probably myosin, with actin filaments, or the force-generating mechanism of the actomyosin-driven intracellular movement, but do not affect actin-filament integrity. PMID- 24212351 TI - Thymine photodimer formation in DNA hairpins. Unusual conformations favor (6 - 4) vs. (2 + 2) adducts. AB - The photochemical reactions of eleven synthetic DNA hairpins possessing a single TT step either in a base-paired stem or in a hexanucleotide linker have been investigated. The major reaction products have been identified as the cis-syn (2 + 2) adduct and the (6 - 4) adduct on the basis of their spectroscopic properties including 1D and 2D NMR spectra, UV spectra and stability or instability to photochemical cleavage. Product quantum yields and ratios determined by HPLC analysis allow the behaviour of the eleven hairpins to be placed into three groups: Group I in which the (2 + 2) adduct is the major product, as is usually the case for DNA, Group II in which comparable amounts of (2 + 2) and (6 - 4) adducts are formed, and Group III in which the major product is the (6 - 4) adduct. The latter behaviour is without precedent in natural or synthetic DNA and appears to be related to the highly fluxional structures of the hairpin reactants. Molecular dynamics simulation of ground state conformations provides quantum yields and product ratios calculated using a single parameter model that are in reasonable agreement with most of the experimental results. Factors which may influence the observed product ratios are discussed. PMID- 24212352 TI - Role of PHGG as a dietary fiber: a review article. AB - AIM: Functional and metabolic effects of dietary fiber are recognized by the scientific, clinical and nutritional experts. Dietary fiber plays a very significant role in modifying the intestinal microbiota, exerting prebiotic effects such as stimulating the growth and/or function of beneficial intestinal microorganisms. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Partially Hydrolyzed Guar Gum (PHGG) is a natural dietary fiber (BenefibraTM, Novartis CH Italy): it is a white powder, water-soluble, colorless and transparent in water solution and almost tasteless. PHGG is stable and soluble at various pH levels commonly found in foods as well as resistant to heat, acid, salt, high pressure and digestive enzymes. Low viscosity of PHGG provides a distinct advantage for the use of fiber in enteral feeding products to be administered through feeding tubes. It has been studied in adults, both healthy volunteers and patients, in different disorders such as constipation, irritable bowel syndrome (IBS), enteral nutrition, small intestine bacterial overgrowth (SIBO) and, very recently, in children suffering from functional abdominal pain according to the Rome III Criteria definition for functional gastrointestinal disorders (FGIDs). This review takes stock of the situation concerning what is known to date on PHGG as dietary fiber, in order to give the health care professionals, such as gastroenterologists, dieticians and general practitioners, a complete overview on its intrinsic characteristics, preclinical and clinical evaluations, uses in different situations as supportive therapy in the management of the main intestinal functional disorders both in adults and in children. METHODS: All the papers on PHGG, published from the early 1990s of the Last Century to the Year 2013, have been considered. All types of publications have been included. PubMed, Medline, Ovid were the main sources adopted for data retrieving. RESULTS: PHGG has been studied in both animals and humans; its safety is well known and several clinical uses are well established. Concerning the modulation of metabolism in human, very little has been done to date and the studies have been focused, for the most part, on the functional diseases: PHGG has been proved to be useful in treating both IBS -C and D symptoms, not only in adults but also in children; data on constipation are relatively scarce and what can be deduced from the Literature is that the high concentration of fiber gives the PHGG the possibility of being used effectively in acceptable dosages (up to 22 g/day) even in situations such as chronic constipation. The use in clinical nutrition has revealed the flexibility of the compound which, owing to its peculiar characteristics, does not gel and remains liquid, PHGG can be used successfully in patients in enteral nutrition lowering the incidence of diarrhea. New open horizons can be glimpsed for SIBO treatment, lowering or maximizing the antibiotics use. CONCLUSION: Not all the fibers are the same: this is a fact. Promoting the specific knowledge of their characteristics is very important if healthcare professionals want to give their patients the best options for functional gastrointestinal disorders or nutritional needs. PHGG (BenefiberTM Novartis CH) has been proved to be safe and effective in promoting gut health. PMID- 24212353 TI - Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. AB - The alcoholic liver disease (ALD) is the leading cause of death from liver failure in Italy and worldwide. Ethanol abstention, a healthy diet, and a significant improvement of life-style are the mainstay of treatment for this disease. Currently, we do not have effective therapeutic options are at our disposal to restore and maintain an improved clinical status. Silymarin is a complementary and alternative medicine often prescribed and self-prescribed; it has anti-oxidant, anti-inflammatory, anti-fibrotic, and metabolic properties. It improves the laboratoristic values and the ultrasonographic grading of liver disease in case of steatosis/steatohepatitis. S-adenosyl-L-methionine (SAMe) is the principal biological methyl donor, and it is also a precursor of glutathione (GSH), essential for the anti-oxidant pathways. SAMe is particularly important for opposing the toxicity of free radicals generated by various toxins, including alcohol. An association between Silymarin and SAMe (labelled as a dietary supplement) has been recently brought to market, and seems to be promising. It could be beneficial in such cases of alcoholic hepathopathies. New therapeutic options are needed by hepatologists to successfully overcome a constantly growing disease. PMID- 24212354 TI - Early diagnosis and management of esophageal and gastric cancer. AB - Esophageal and gastric cancers have high mortality rates secondary to the late presentation of most patients at advanced stages. Improved survival is achievable when the disease is confined to the more superficial mucosal layers and treated. This review will focus on the detection, screening, staging, endoscopic treatment, and surveillance of early upper gastrointestinal cancer - squamous cell carcinoma of the esophagus, esophageal adenocarcinoma, and gastric adenocarcinoma. PMID- 24212355 TI - Endoscopic ultrasound-guided radiation therapy in pancreatic cancer. AB - During the last two decades, endoscopic ultrasound has revolutionized the diagnosis and treatment of gastrointestinal (GI) malignancies. The role of EUS has expanded well beyond its role as a diagnostic modality, and has emerged as a highly sophisticated interventional modality. More recently, EUS has paved its way into radiation oncology by either facilitating highly targeted image guided radiotherapy (IGRT) by insertion of fiducial markers in tumors or by direct instillation of radioactive seeds (brachytherapy). Although the experience regarding these techniques is in a preliminary stage, if developed further, this can potentially provide a highly accurate and minimally invasive approach for implantation of fiducial and radioactive seeds. This review will discuss potential role of EUS in implantation therapy, current literature and also speculate on future prospects for these EUS-guided interventions in pancreatic cancer. PMID- 24212356 TI - Endoscopic resolution of secondary complications in bariatric surgery. AB - Morbid obesity has become an epidemic in past few decades. It has become an important aspect of public health-focused issues due its impact on several chronic diseases, including diabetes and cardiovascular diseases. Consequently the number of bariatric surgeries have increased in the past few years due to improved techniques and devices. A multidisciplinary approach such as surgical intervention and diet modification has yielded effective and sustainable weight loss in morbidly obese patients. However, as with as surgical procedure, immediate and long term complications may occur after bariatric surgery. Approximately 5% to 10% of patients who undergo bariatric surgery develop early complications (also known as perioperative complications), those that appear within the first 30 days of surgery, and 9% to 25% show sign of problems after the initial 30 days (late complications). Complications of bariatric surgery are related to the type of procedure performed and this review will describe the most common complication and their endoscopic management. PMID- 24212357 TI - High internal phase emulsion (HIPE) organogels prepared from charge-driven assembled polymer organogels. AB - We prepared HIPE organogels from polymer organogels which were pre-formed based on a triblock ionomer and polypropylenimine dendrimers via charge-induced assembly. The morphologies of the HIPE organogels are little changed with salt concentrations while the mechanical strength of the organogels can be tuned by PPI dendrimers. PMID- 24212358 TI - Health technology assessments in England: an analysis of the NICE Medical Technologies Evaluation Programme. PMID- 24212359 TI - The application of digital volume correlation (DVC) to study the microstructural behaviour of trabecular bone during compression. AB - Digital Volume Correlation (DVC) has been emerged recently as an innovative approach to full volume (i.e. internal) displacement and strain field measurement in materials and structures, particularly in conjunction with high resolution X ray computed tomography (CT). As a relatively novel technique certain aspects of precision, accuracy and the breadth of application are yet to be fully established. This study has applied DVC to volume images of porcine trabecular bone assessing the effect of noise and sub-volume size on strain measurement. Strain resolutions ranging between 70 and 800MUepsilon were obtained for the optimum sub-volume size of 64 voxels with a 50% overlap for metrological studies conducted. These values allowed the mechanical behaviour of porcine trabecular bone during compression to be investigated. During compression a crushed layer formed adjacent to the boundary plate which increased in thickness as the specimen was further deformed. The structure of the crushed layer was altered to such an extent that it confounded the correlation method. While investigating this factor, it was found that for reliable strain calculations a correlation coefficient of 0.90 or above was required between the sub-volumes in the reference and the deformed volumes. Good agreements between the results and published bone strain failures were obtained. Using the full field strain measurements, Poisson's ratio was identified for each compression step using a dedicated inverse method called the virtual fields method (VFM). It was found that for a given region outside of the crushed zone the Poisson ratio decreased from 0.32 to 0.21 between the first and the final compression steps, which was hypothesised to be due to the bone geometry and its resulting deformation behaviour. This study demonstrates that volumetric strain measurement can be obtained successfully using DVC, making it a useful tool for quantitatively investigating the micro-mechanical behaviour of macroscale bone specimens. PMID- 24212360 TI - Evaluation of cranial window types for in vivo two-photon imaging of brain microstructures. AB - In vivo two-photon laser scanning microscopy (2PLSM) of neurons and glia in the mouse neocortex can be achieved using two distinct surgical methods: the thin skull and open-skull window techniques. The open-skull window technique is more invasive, but provides more flexibility in imaging periods and frequencies. Critical evaluations of the two surgical methods are required, particularly their ability to image submicron structures such as dendritic filopodia and spines. Here, we used multiple approaches to evaluate the optical resolution of 2PLSM through two types of cranial windows. Two-photon point spread function (PSF) on the surface of the neocortex in vivo was studied by imaging the fluorescent microspheres attached to the pial surface. Comparable PSF widths indicated that the optical resolution of 2PLSM on the brain surface was similar between the two types of cranial window techniques. Next, we evaluated the effects of laser beam propagation through the thinned bone by imaging the underlying gel samples containing fluorescent microspheres as phantoms mimicking the brain tissue. We observed deterioration of PSF with increase in the imaging depths through the thinned bone. Reduction in image resolution through the thin-skull window in the deep cortical layer was confirmed by repetitive 2PLSM of the same GFP-positive dendritic spines with two techniques. In summary, the resolution of 2PLSM is comparable with those of two cranial window preparations in the superficial layer of the neocortex, but the quality of the image through the thin-skull windows degrades at points deeper than 50 um. PMID- 24212361 TI - GP league tables are too simple and should not be used, says BMA. PMID- 24212362 TI - Adaptive response to sociality and ecology drives the diversification of facial colour patterns in catarrhines. AB - The faces of Old World monkeys and apes (Catarrhini) exhibit every possible hue in the spectrum of mammal colours. Animal colouration experiences selection for communication, physiology and ecology; however, the relative importance of these factors in producing facial diversity in catarrhines is not known. Here we adopt a comparative approach to test whether facial traits have evolved in tandem with social, geographic and ecological pressures across four catarrhine radiations. Our analyses reveal the underlying correlates of two major axes in the evolution of facial diversity. Facial colour patterns are linked to social factors, such that gregarious and highly sympatric species have evolved more colours in their faces. Facial pigmentation tends to be dominated by ecological factors, and species living in tropical, densely forested and humid habitats in Africa have evolved darker faces. Thus, both sociality and ecology have played a role in producing the highest diversity of faces within mammals. PMID- 24212363 TI - Sports Medicine & Arthroscopy Review. Editorial. PMID- 24212364 TI - The basic science of platelet-rich plasma (PRP): what clinicians need to know. AB - Platelet-rich plasma (PRP) has been advocated for the biological augmentation of tissue healing and regeneration through the local introduction of increased levels (above baseline) of platelets and their associated bioactive molecules. In theory, the increased levels of autologous growth factors and secretory proteins provided by the concentrated platelets may enhance the wound healing process, especially in degenerative tissues or biologically compromised individuals. Although PRP has been increasingly utilized in the treatment of a variety of sports-related injuries, improvements in healing and clinical outcomes have not been universally reported. One reason for this may be the fact that all PRP preparations are not the same. Variations in the volume of whole blood taken, the platelet recovery efficacy, the final volume of plasma in which the platelets are suspended, and the presence or absence of white blood cells, and the addition of exogenous thrombin to activate the platelets or calcium chloride to induce fibrin formation, can all affect the character and potential efficacy of the final PRP product. This article will review the basic principles involved in creating PRP and examine the potential basic scientific significance of the individual blood components contained in the various forms of PRP currently used in sports medicine. PMID- 24212365 TI - Variability of platelet-rich plasma preparations. AB - Platelet-rich plasma (PRP) as a clinical treatment for bone, muscle, tendon, and cartilage injury has gained popularity in the field of orthopedic sports medicine. The use of a patient's own blood is an appealing aspect of PRP treatment, as the resulting plasma preparation is considered relatively benign in comparison with more common, potentially caustic treatments such as corticosteroids and anesthetics. Although appealing, the autologous nature of PRP introduces variability to plasma preparations, creating challenges for both the researcher and the clinician. Differences in patients at the time of blood draw result in plasma preparations that vary within as well as between patients. This variability is compounded by the multitude of protocols and devices available for procuring PRP. The variability of components and its effects on dosage should be considered in single or consecutive treatments of PRP. PMID- 24212366 TI - Platelet-rich plasma for muscle injury and tendinopathy. AB - Platelet-rich plasma (PRP) is increasingly used in Regenerative Medicine. The concept of PRP as a natural source of signaling molecules with paracrine effects in different cells is the basis for the increased PRP application as treatment for sports injuries. PRP recapitulates the principal functions of the natural healing response in orchestrating cell proliferation, differentiation, migration, and angiogenesis. After systematically searching the literature, we identified 21 trials for PRP injections in tendinopathy: 57% were uncontrolled trials and 1 cohort study in muscle. Leukocyte-PRP was used in 91.7% of tendons, of which 65.5% received 1 single injection. Given the lack of large controlled trials, it is clear that the effectiveness of conservative L-PRP treatments is not proven. The clinical evaluation of alternative formulations can be extremely informative. Other unexplored issues include activation, redosing, and concomitant longitudinal tenotomies. Limiting factors for the acceptance of PRP are the lack of evidence of obvious clinical improvement and reimbursement. PMID- 24212367 TI - Platelet-rich plasma for rotator cuff repair. AB - Rotator cuff tears are a common cause of shoulder pain and disability. Because they combine both traumatic and degenerative elements, the surgical repair can be challenging. Even after surgical intervention, tendon residual defects or "retears" often develop. Risk factors for tendon "retears" include patient age, number of tendons involved, tear size, and smoking. Platelet-rich plasma (PRP) is a supraphysiological concentration of platelets, which may be able to positively augment rotator cuff tendon healing. Not all PRPs are the same and those containing higher leukocyte levels may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors from the PRP and may actually inhibit some parts of the healing response. As yet, the clinical data does not conclusively prove a benefit from PRP, but discernment is required in evaluating the published results. As different PRPs may act differently and the results may be dose dependent requiring more PRP to achieve a beneficial threshold. How success is measured (clinical outcomes vs. intact cuff tendons) and how long the patients are followed are also critical items. Currently, the PRP fibrin matrix version holds the greatest promise for improving clinical success after rotator cuff tendon repair. PMID- 24212368 TI - The use of PRP in ligament and meniscal healing. AB - Platelet-rich plasma (PRP) has become a popular treatment for acute and chronic soft tissue injuries. Although the majority of research has focused on its use in tendinopathy, PRP may have potential in meniscus and ligament healing. Some level II studies support a possible benefit for anterior cruciate ligament (ACL) allograft maturation, and preliminary animal studies point to a potential role for PRP in primary ACL repair. However, randomized controlled trials have not demonstrated a benefit of PRP for ACL tendon allograft-tunnel integration. To date, 2 studies document the use of PRP for meniscal applications, but this field is largely unexplored. With respect to ligament and meniscal applications, the current literature suggests PRP may be promising for primary ACL repair in skeletally immature patients, ACL graft maturation, and repair of meniscal tears in the avascular zone. PMID- 24212369 TI - Platelet-rich plasma for articular cartilage repair. AB - Platelet concentrates have been gaining popularity for a number of applications in orthopedic surgery as a way to enhance both healing of various tissues and reduce pain. One major area of focus has been the effect of platelet-rich plasma (PRP) on stem cells and chondrocytes and the potential for PRP to enhance cartilage regeneration as well as reduce catabolic factors that lead to cartilage degradation. This article provides an up-to-date review of the current literature regarding the effect of PRP on articular cartilage and its use in the treatment of osteoarthritis. Basic science, animal, and human clinical investigations are presented. In general, PRP has been shown to promote chondrogenic differentiation in vitro and lead to enhanced cartilage repair during animal investigations. Human trials, mostly conducted in the form of injection into knees with osteoarthritis, have shown promise in a number of investigations for achieving symptomatic relief of pain and improving function. PMID- 24212370 TI - Platelet-rich plasma and plantar fasciitis. AB - Plantar fasciitis is the most common cause of heel pain and can prove difficult to treat in its most chronic and severe forms. Advanced cases of plantar fasciitis are often associated with ankle stiffness, heel spurs, and other conditions and can lead to extensive physical disability and financial loss. Most available traditional treatments, including orthoses, nonsteroidal anti inflammatory drugs, and steroid injections have a paucity of supportive clinical evidence. More invasive treatments, ranging from corticosteroid and botulinum-A toxin injections to shockwave therapy and plantar fasciotomy, have demonstrated varying clinical success in severe cases but carry the potential for serious complication and permanent disability. Platelet-rich plasma has recently been demonstrated to be helpful in managing chronic severe tendinopathies when other techniques have failed. This review examines the pathophysiology, diagnostic options, nonoperative treatment modalities, and surgical options currently used for plantar fasciitis. It also focuses on the clinical rationale and available evidence for using autologous platelet-rich plasma to treat severe refractory chronic plantar fasciitis. PMID- 24212371 TI - The use of platelet-rich plasma in orthopedic injuries. AB - Platelet-rich plasma (PRP) is an autologous concentration of blood-derived human platelets in a small volume of plasma. The types of PRP vary according to the commercial preparation system used, the platelet concentration, or the anticoagulant or activator used. Autologous conditioned plasma is an autologous concentration of human platelets in plasma 2 to 4 times greater than that which is found in blood at baseline. Platelets are important to the normal healing response of tissue by the local secretion of growth factors and recruitment of reparative cells in an area of injury. PRP is theorized to create an optimal healing environment in a region of tissue injury. This is a literature review of currently published studies using PRP in orthopedic injuries. We performed a literature search in PubMed and Medline in April 2013. We concluded that given the number of variations of PRP available and the lack of high-level published studies, there is insufficient evidence to conclusively support its clinical use. PMID- 24212374 TI - Development of a FRET biosensor with high specificity for Akt. AB - The serine/threonine kinase Akt plays a critical role in cell proliferation, survival, and tumorigenesis. As a central kinase in the phosphatidylinositol 3 kinase pathway, its activation mechanism at the plasma membrane has been well characterized. However, the subcellular Akt activity in living cells is still largely unknown. Fluorescence resonance energy transfer (FRET)-based biosensors have emerged as indispensable tools to visualize the subcellular activities of signaling molecules. In this study, we developed a highly specific FRET biosensor for Akt based on the Eevee backbone, called Eevee-iAkt. Using inhibitors targeting kinases upstream and downstream of Akt, we showed that Eevee-iAkt specifically monitors Akt activity in living cells. To visualize Akt activity at different subcellular compartments, we targeted Eevee-iAkt to raft and non-raft regions of the plasma membrane, mitochondria, and nucleus in HeLa and Cos7 cells. Interestingly, we revealed substantial differences in Akt activation between HeLa and Cos7 cells upon epidermal growth factor (EGF) stimulation: Akt was transiently activated in HeLa cells with comparable levels at the plasma membrane, cytosol, and mitochondria. In contrast, sustained and spatially localized Akt activation was observed in EGF-stimulated Cos7 cells. We found high Akt activity at the plasma membrane, low activity in the cytosol, and no detectable activity at the mitochondria and nucleus in Cos7 cells. The Eevee-iAkt biosensor was shown to be a valuable tool to study the functional relationship between subcellular Akt activation and its anti-apoptotic role in living cells. PMID- 24212375 TI - Localization of angulin-1/LSR and tricellulin at tricellular contacts of brain and retinal endothelial cells in vivo. AB - The paracellular pathway of an epithelial cellular sheet can be divided into two parts: one between two adjacent cells sealed by tight junctions (TJs) and one at tricellular contacts (TCs), where the corners of three cells meet. At TCs of epithelial cells, there is a specialized mode of TJs, namely tricellular TJs (tTJs), required for full barrier function of the cellular sheet. However, tTJs have not been described in endothelial cells to date. Here, we investigated whether tTJs occur in endothelial cells by analyzing the TC localizations of tTJ markers, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1, and angulin-3/ILDR2), by immunofluorescence staining of frozen sections of various tissues from adult mice. Endothelial TCs in most tissues revealed no detectable staining of tricellulin or angulins. However, tricellulin and angulin 1/LSR were specifically concentrated in TCs of brain and retinal endothelial cells, which form the blood-brain barrier (BBB) and inner blood-retinal barrier (BRB), respectively. Even in the brain, endothelial cells in the choroid plexus and the median eminence, one of the circumventricular organs, did not show concentration of tricellulin or angulins at TCs. These findings indicate the existence of tTJs in endothelial cells in vivo and suggest that tTJs impart important characteristics to the BBB and inner BRB. PMID- 24212376 TI - The role of lymphatic transport on the systemic bioavailability of the Bcl-2 protein family inhibitors navitoclax (ABT-263) and ABT-199. AB - Navitoclax (ABT-263), a Bcl-2 family inhibitor and ABT-199, a Bcl-2 selective inhibitor, are high molecular weight, high logP molecules that show low solubility in aqueous media. While these properties are associated with low oral bioavailability (F), both navitoclax and ABT-199 showed moderate F in preclinical species. The objective of the described study was to determine if lymphatic transport contributes to the systemic availability of navitoclax and ABT-199 in dogs. The intravenous pharmacokinetics of navitoclax and ABT-199 were determined in intact (noncannulated) dogs. In oral studies, tablets (100 mg) of navitoclax and ABT-199 were administered to both intact and thoracic lymph duct-cannulated (TDC) dogs. The clearance of navitoclax and ABT-199 was low; 0.673 and 0.779 ml/min per kilogram, respectively. The volume of distribution of both compounds was low (0.5-0.7 l/kg). The half-lives of navitoclax and ABT-199 were 22.2 and 12.9 hours, respectively. The F of navitoclax and ABT-199 were 56.5 and 38.8%, respectively, in fed intact dogs. In fed TDC dogs, 13.5 and 4.67% of the total navitoclax and ABT-199 doses were observed in lymph with the % F of navitoclax and ABT-199 of 21.7 and 20.2%, respectively. The lower lymphatic transport of ABT 199 corresponds to the lower overall % F of ABT-199 versus navitoclax despite similar systemic availability via the portal vein (similar % F in TDC animals). This is consistent with the higher long chain triglyceride solubility of navitoclax (9.2 mg/ml) versus ABT-199 (2.2 mg/ml). In fasted TDC animals, lymph transport of navitoclax and ABT-199 decreased by 1.8-fold and 10-fold, respectively. PMID- 24212377 TI - Impact of endogenous esterase activity on in vitro p-glycoprotein profiling of dabigatran etexilate in Caco-2 monolayers. AB - Dabigatran etexilate, a double prodrug of dabigatran, is a reversible, competitive, direct thrombin inhibitor that has been approved for use in many countries. A recent guideline from the European Medicines Agency on drug-drug interactions proposed dabigatran etexilate as a sensitive in vivo and in vitro probe substrate for intestinal P-glycoprotein (P-gp) inhibition. We therefore performed a series of in vitro studies to determine the best experimental conditions for evaluation of P-gp involvement on the transport process of dabigatran etexilate across colorectal adenocarcinoma Caco-2 cell monolayers. Experiments using expressed carboxylesterase 1 (CES1) and CES2 bactosomes revealed that dabigatran etexilate was hydrolyzed into BIBR 1087 by CES1 expressed in our Caco-2 cells. The impact of CES1-mediated BIBR 1087 formation during transcellular transport experiments was assessed by comparing several combinations of three experimental approaches: radioactivity detection using [(14)C]dabigatran etexilate as substrate, liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification of dabigatran etexilate, and in the presence and absence of a CES inhibitor bis(p-nitrophenyl) phosphate (BNPP). The experimental approach that was based on the use of nonlabeled dabigatran etexilate together with LC-MS/MS quantification and the addition of BNPP was selected as the most favorable condition in which to correctly evaluate the permeability coefficient (Papp) of dabigatran etexilate and its transcellular transport by P-gp. The in vitro Caco-2 study at the selected condition revealed that dabigatran etexilate is a P-gp substrate with an efflux ratio of 13.8 and an intrinsic Papp, which is the Papp under the condition of complete blockage of P gp by P-gp inhibitor, of 29 * 10(-6) cm/s. PMID- 24212378 TI - In vitro predictability of drug-drug interaction likelihood of P-glycoprotein mediated efflux of dabigatran etexilate based on [I]2/IC50 threshold. AB - Dabigatran etexilate, an oral, reversible, competitive, and direct thrombin inhibitor, is an in vitro and in vivo substrate of P-glycoprotein (P-gp). Dabigatran etexilate was proposed as an in vivo probe substrate for intestinal P gp inhibition in a recent guidance on drug-drug interactions (DDI) from the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). We conducted transcellular transport studies across Caco-2 cell monolayers with dabigatran etexilate in the presence of various P-gp inhibitors to examine how well in vitro IC50 data, in combination with mathematical equations provided by regulatory guidances, predict DDI likelihood. From a set of potential P-gp inhibitors, clarithromycin, cyclosporin A, itraconazole, ketoconazole, quinidine, and ritonavir inhibited P-gp-mediated transport of dabigatran etexilate over a concentration range that may hypothetically occur in the intestine. IC50 values of P-gp inhibitors for dabigatran etexilate transport were comparable to those of digoxin, a well established in vitro and in vivo P-gp substrate. However, IC50 values varied depending whether they were calculated from efflux ratios or permeability coefficients. Prediction of DDI likelihood of P-gp inhibitors using IC50 values, the hypothetical concentration of P-gp inhibitors, and the cut-off value recommended by both the FDA and EMA were in line with the DDI occurrence in clinical studies with dabigatran etexilate. However, it has to be kept in mind that validity of the cut-off criteria proposed by the FDA and EMA depends on in vitro experimental systems and the IC50-calculation methods that are employed, as IC50 values are substantially influenced by these factors. PMID- 24212379 TI - Identification of carboxylesterase-dependent dabigatran etexilate hydrolysis. AB - Dabigatran etexilate (DABE) is an oral prodrug that is rapidly converted to the active thrombin inhibitor, dabigatran (DAB), by serine esterases. The aims of the present study were to investigate the in vitro kinetics and pathway of DABE hydrolysis by human carboxylesterase enzymes, and the effect of alcohol on these transformations. The kinetics of DABE hydrolysis in two human recombinant carboxylesterase enzymes (CES1 and CES2) and in human intestinal microsomes and human liver S9 fractions were determined. The effects of alcohol (a known CES1 inhibitor) on the formation of DABE metabolites in carboxylesterase enzymes and human liver S9 fractions were also examined. The inhibitory effect of bis(4 nitrophenyl) phosphate on the carboxylesterase-mediated metabolism of DABE and the effect of alcohol on the hydrolysis of a classic carboxylesterase substrate (cocaine) were studied to validate the in vitro model. The ethyl ester of DABE was hydrolyzed exclusively by CES1 to M1 (Km 24.9 +/- 2.9 MUM, Vmax 676 +/- 26 pmol/min per milligram protein) and the carbamate ester of DABE was exclusively hydrolyzed by CES2 to M2 (Km 5.5 +/- 0.8 MUM; Vmax 71.1 +/- 2.4 pmol/min per milligram protein). Sequential hydrolysis of DABE in human intestinal microsomes followed by hydrolysis in human liver S9 fractions resulted in complete conversion to DAB. These results suggest that after oral administration of DABE to humans, DABE is hydrolyzed by intestinal CES2 to the intermediate M2 metabolite followed by hydrolysis of M2 to DAB in the liver by CES1. Carboxylesterase-mediated hydrolysis of DABE was not inhibited by alcohol. PMID- 24212381 TI - Protein restoration in low-birth-weight rat offspring derived from maternal low protein diet leads to elevated hepatic CYP3A and CYP2C11 activity in adulthood. AB - The World Health Organization has identified hypercholesterolemia to be one of the major symptoms encompassing the metabolic syndrome. Moreover, epidemiologic evidence indicates that low-birth-weight offspring are at greater risk of developing the metabolic syndrome. Previous work in our laboratory demonstrated that maternal protein restriction (MPR) results in impaired fetal growth and hypercholesterolemia in adulthood. This was attributed to repression of hepatic CYP7A1, a rate-limiting enzyme that catabolizes cholesterol to bile acids. Another important function of hepatic cytochrome P450 enzymes is the phase I oxidative metabolism of drugs (i.e., statins for hypercholesterolemia), which can significantly impact pharmacokinetics. We hypothesized that MPR offspring may have altered ability to metabolize drugs in adulthood. To address this hypothesis, we maintained Wistar rats on a 20% protein diet (control) or a low 8% protein diet throughout prenatal and postnatal life (LP1) or exclusively during prenatal life and weaning (LP2). Intriguingly CYP3A and CYP2C11 intrinsic clearance (Vmax/Km) was significantly increased exclusively in LP2 offspring at postnatal day 130 compared with control or LP1 offspring, as evaluated by testosterone enzyme kinetics in liver microsomes. The increase in activity was secondary to an increase in CYP3A23 and CYP2C11 mRNA. Collectively, these findings suggest that a low-birth-weight offspring with postnatal catch-up growth may have a diminished response to xenobiotics metabolized by CYP3A and CYP2C11 enzymes. PMID- 24212380 TI - CPY3A4-mediated alpha-hydroxyaldehyde formation in saquinavir metabolism. AB - Saquinavir (SQV) is a protease inhibitor widely used for the treatment of human immunodeficiency virus (HIV) infection. We profiled SQV metabolism in mice using a metabolomic approach. Thirty SQV metabolites were identified in mouse feces and urine, of which 20 are novel. Most metabolites observed in mice were recapitulated in human liver microsomes. Among these novel metabolites, one alpha hydroxyaldehyde produced from SQV N-dealkylation was noted and verified for the first time. Meanwhile, the corresponding product (3S)-N-tert-butyldecahydro isoquinoline-3-carboxamide and its further metabolites were identified in mouse urine. The alpha-hydroxyaldehyde pathway was confirmed by using semicarbazide as a trapping reagent as well. Using recombinant cytochrome P450 (CYP450) isoenzymes and Cyp3a-null mice, CYP3A was identified as the dominant enzyme contributing to the formation of alpha-hydroxyaldehyde. This study enhances our knowledge of SQV metabolism, which can be used for predicting drug-drug interactions and further understanding the mechanism of adverse effects associated with SQV. PMID- 24212382 TI - Evaluation of intrinsic charge carrier transport at insulator-semiconductor interfaces probed by a non-contact microwave-based technique. AB - We have successfully designed the geometry of the microwave cavity and the thin metal electrode, achieving resonance of the microwave cavity with the metal insulator-semiconductor (MIS) device structure. This very simple MIS device operates in the cavity, where charge carriers are injected quantitatively by an applied bias at the insulator-semiconductor interface. The local motion of the charge carriers was clearly probed through the applied external microwave field, also giving the quantitative responses to the injected charge carrier density and charge/discharge characteristics. By means of the present measurement system named field-induced time-resolved microwave conductivity (FI-TRMC), the pentacene thin film in the MIS device allowed the evaluation of the hole and electron mobility at the insulator-semiconductor interface of 6.3 and 0.34 cm2 V-1 s-1, respectively. This is the first report on the direct, intrinsic, non-contact measurement of charge carrier mobility at interfaces that has been fully experimentally verified. PMID- 24212383 TI - Role of endomyocardial biopsy for children presenting with acute systolic heart failure. AB - Myocarditis, an inflammatory disease of the heart, frequently results from viral infections, postviral immune-mediated responses, or both. It is a common cause of acute-onset systolic heart failure in children. Endomyocardial biopsy (EMB) remains the gold standard for the diagnosis of myocarditis. However, EMB is not performed for most myocarditis cases involving children in the United States. Clinical scenarios in which EMB results added unique prognostic data and guidance to therapy have been defined recently. This review outlines the role of EMB in the diagnosis and management of myocarditis for children presenting with acute onset systolic heart failure. PMID- 24212384 TI - Ischemic stroke after use of the synthetic marijuana "spice". AB - OBJECTIVES: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as "spice" (a synthetic marijuana product, also known as "K2"), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. METHODS: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. RESULTS: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. CONCLUSIONS: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions. PMID- 24212386 TI - Comment: a reappraisal of juvenile myoclonic epilepsy. PMID- 24212385 TI - Long-term predictive value of the Framingham Risk Score for Stroke in HIV positive vs HIV-negative men. AB - OBJECTIVE: To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men. METHODS: The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status. RESULTS: A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV- participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV- MSM (6.6% [range 3%-26%] vs 4.9% for HIV+ MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants. CONCLUSIONS: FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men. PMID- 24212387 TI - CSF biomarkers of Alzheimer disease: "noncognitive" outcomes. AB - OBJECTIVES: To test whether CSF Alzheimer disease biomarkers (beta-amyloid 42 [Abeta42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Abeta42, and ptau181/Abeta42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. METHODS: Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. RESULTS: Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. CONCLUSIONS: CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples. PMID- 24212388 TI - Basal ganglia involvement in amyotrophic lateral sclerosis. AB - OBJECTIVES: To characterize the nature and extent of basal ganglia involvement in amyotrophic lateral sclerosis (ALS) genotypes in vivo. METHODS: Forty-four healthy controls and 39 patients with ALS were included in the study. Thirty patients with ALS had a negative C9orf72 status and 9 patients with ALS carried the C9orf72 hexanucleotide repeat expansion. High-resolution T1-weighted MRI data were used for model-based subcortical registration and segmentation. Fifteen subcortical structures were studied with both volumetric and vertex-wise approaches. Changes in basal ganglia diffusivity parameters were also assessed. RESULTS: Using age as a covariate, patients with ALS who were C9orf72 repeat negative showed significant volume reductions in the left caudate nucleus (p = 0.01), left hippocampus (p = 0.007), and right accumbens nucleus (p = 0.001) compared with healthy controls. Vertex-wise shape analyses revealed changes affecting the superior and inferior aspects of the bilateral thalami, the lateral and inferior portion of the left hippocampus, and the medial and superior aspect of the left caudate. Basal ganglia pathology was more extensive in patients with ALS carrying the C9orf72 hexanucleotide repeat expansion. CONCLUSIONS: ALS is associated with widespread basal ganglia involvement. Caudate nucleus, hippocampus, and nucleus accumbens atrophy are key features of ALS. Dysfunction of frontostriatal networks is likely to contribute to the unique neuropsychological profile of ALS, dominated by executive dysfunction, apathy, and deficits in social cognition. Our quantitative imaging findings are consistent with postmortem studies and indicate that subcortical gray matter structures should be included in future biomarker studies of ALS. PMID- 24212389 TI - Very early pattern of movement disorders in sepiapterin reductase deficiency. PMID- 24212391 TI - Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. AB - OBJECTIVES: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy. However, little is known about the long term medical evolution of this clinical entity. The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome. METHODS: In this retrospective cohort study, we analyzed seizure outcome in 66 patients who had JME, were treated at the Department of Neurology, Charite-Universitatsmedizin Berlin, and were initially diagnosed by a single senior epileptologist. RESULTS: After a mean follow-up time of 44.6 years (20-69 years), 59.1% of patients remained free of seizures for at least 5 years before the last contact. Among the seizure-free patients, 28 (71.8%) were still taking antiepileptic drugs and 11 (28.2%) were off medication for at least the last 5 years. We identified manifestation of additional absence seizures at onset of JME as an independent predictor of an unfavorable outcome regarding seizure freedom. CONCLUSIONS: A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome. PMID- 24212390 TI - Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies. AB - OBJECTIVE: To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB). METHODS: We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range 2-12 years). Competing risks survival models were used to examine the rates of progression to clinically probable DLB and Alzheimer disease (AD). A subset of patients underwent neuropathologic examination. RESULTS: In this clinical cohort, 116 remained as MCI, while 49 progressed to probable DLB, 162 progressed to clinically probable AD, and 10 progressed to other dementias. Among nonamnestic MCI, progression rate to probable DLB was 20 events per 100 person-years and to probable AD was 1.6 per 100 person-years. Among amnestic MCI, progression rate to probable AD was 17 events per 100 person-years, and to DLB was 1.5 events per 100 person-years. In 88% of those who developed probable DLB, the baseline MCI diagnosis included attention and/or visuospatial deficits. Those who developed probable DLB were more likely to have baseline daytime sleepiness and subtle parkinsonism. In 99% of the clinically probable AD group, the baseline MCI diagnosis included memory impairment. Neuropathologic confirmation was obtained in 24 of 30 of those with clinically probable AD, and in 14 of 18 of those with clinically probable DLB. CONCLUSION: In a clinical sample, patients with nonamnestic MCI were more likely to develop DLB, and those with amnestic MCI were more likely to develop probable AD. PMID- 24212392 TI - Spice, pot, and stroke. AB - The endocannabinoid system includes 2 types of G-protein coupled receptors: CB1 (mostly in the brain) and CB2 (in peripheral lymphoid tissue). The major cannabinoid ligands are arachidonylethanolamine ("anandamide," the Sanskrit word for bliss) and 2-arachidonylglycerol ("2AG"). It is by binding to CB1 receptors that delta-9-tetrahydrocannabinol (THC), the principal psychoactive ingredient in marijuana ("pot"), produces its intended subjective effects. PMID- 24212393 TI - An RCT to treat learning impairment in multiple sclerosis: The MEMREHAB trial. AB - OBJECTIVE: To examine the efficacy of the modified Story Memory Technique (mSMT), a 10-session behavioral intervention teaching context and imagery to facilitate learning, to improve learning and memory abilities in persons with multiple sclerosis (MS). METHODS: This double-blind, placebo-controlled, randomized clinical trial included 86 participants with clinically definite MS, 41 in the treatment group and 45 in the placebo control group. Participants completed a baseline neuropsychological assessment, including questionnaires assessing everyday memory, a repeat assessment immediately posttreatment, and a long-term follow-up assessment 6 months after treatment. After completion of the treatment phase, persons in the treatment group were assigned to a booster session or a non booster session group to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. RESULTS: The treatment group showed a significantly improved learning slope relative to the placebo group posttreatment. Similar results were noted on objective measures of everyday memory, general contentment, and family report of apathy and executive dysfunction. Long-term follow-up data showed that posttreatment improvement in the treatment group continued to be noted on the list learning and self-report measures. The provision of booster sessions demonstrated little benefit. CONCLUSION: The mSMT is effective for improving learning and memory in MS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in patients with MS over 5 weeks, with treatment effects lasting over a 6-month period. PMID- 24212394 TI - Abnormal brain maturation in preterm neonates associated with adverse developmental outcomes. AB - OBJECTIVE: Our objective was to determine the association of early brain maturation with neurodevelopmental outcome in premature neonates. METHODS: Neonates born between 24 and 32 weeks' gestation (April 2006 to August 2010) were prospectively studied with MRI early in life and again at term-equivalent age. Using diffusion tensor imaging and magnetic resonance spectroscopic imaging, fractional anisotropy (FA) (microstructure) and N-acetylaspartate (NAA)/choline (metabolism) were measured from the basal nuclei, white matter tracts, and superior white matter. Brain maturation is characterized by increasing FA and NAA/choline from early in life to term-equivalent age. In premature neonates, systemic illness and critical care therapies have been linked to abnormalities of these measures. Of the 177 neonates in this cohort, 5 died and 157 (91% of survivors) were assessed at 18 months' corrected age (adjusted for prematurity) using the Bayley Scales of Infant and Toddler Development III motor, cognitive, and language composite scores (mean = 100, SD = 15). RESULTS: Among these 157 infants, white matter injury was seen in 48 (30%). Severe white matter injury, in 10 neonates (6%), was associated with a decrease in motor (-18 points; p < 0.001) and cognitive (-8 points; p = 0.085) scores. With greater severity of adverse neurodevelopmental outcomes, slower increases in FA and NAA/choline were observed in the basal nuclei and brain white matter regions as neonates matured to term equivalent age, independent of the presence of white matter injury. CONCLUSIONS: In the preterm neonate, abnormal brain maturation evolves through the period of neonatal intensive care and is associated with adverse neurodevelopmental outcomes. PMID- 24212396 TI - Let's rehabilitate cognitive rehabilitation in multiple sclerosis. AB - Up to 60% of patients with multiple sclerosis (MS) experience cognitive dysfunction, with prominent involvement of complex attention, information processing speed, executive functions, episodic memory, and visuospatial abilities. Since MS-related cognitive deficits can substantially affect a wide range of daily life activities (e.g., work, driving, social integration, and adherence to medication regimens), it is imperative that we identify and develop strategies to alleviate them. PMID- 24212395 TI - Is IVIg therapy warranted in progressive lower motor neuron syndromes without conduction block? AB - OBJECTIVE: To evaluate the likelihood of response to IV immunoglobulin (IVIg) by studying consecutive patients presenting with progressive, asymmetric, pure lower motor neuron (LMN) limb weakness, and to determine the clinical phenotype of those who respond. METHODS: Thirty-one consecutive patients with progressive, focal-onset LMN limb weakness, without evidence of clinical upper motor neuron signs; sensory, respiratory, or bulbar involvement; or evidence of motor nerve conduction block on electrodiagnostic studies, were prospectively included in this study. Each patient underwent treatment with IVIg (2 g/kg) for a minimum of 3 months. Electrodiagnostic studies, a neuromuscular symptom score, and expanded Medical Research Council sum score were documented before and after IVIg treatment. The final diagnosis was determined after prolonged clinical follow-up. RESULTS: Only 3 of 31 patients (10%) responded to IVIg. All responders demonstrated distal upper limb-onset weakness, EMG abnormalities confined to the clinically weak muscles, and a normal creatine kinase. This set of features was also identified in 31% of nonresponders presenting with distal upper limb weakness. Sex, age at onset, number of involved limb regions, and the duration of symptoms before treatment were not significantly different between groups. CONCLUSION: The findings of the present study do not support uniform use of IVIg in patients presenting with progressive asymmetric LMN limb weakness. It is suggested that IVIg treatment be limited to patients who demonstrate clinical and laboratory features suggestive of multifocal motor neuropathy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IVIg will not improve muscle function in 90% of patients with progressive, asymmetric, pure LMN weakness. PMID- 24212397 TI - Value of sequential MRI in preterm infants. AB - Since the introduction of neonatal intensive care in the 1970s, there has been a pronounced decrease in overall mortality of premature infants as well as a decrease in the incidence of severe white matter injury, best known as cystic periventricular leukomalacia (c-PVL).(1) While cranial ultrasonography readily visualizes large lesions in the white matter (periventricular hemorrhagic infarction and c-PVL), this technique is not sufficiently sensitive to recognize the much more common and less severe noncystic white matter lesions.(2) The absolute number of extremely preterm infants is increasing because of improved survival rates.(e1.) PMID- 24212398 TI - Reduced expression of hsa-miR-27a-3p in CSF of patients with Alzheimer disease. AB - OBJECTIVE: We evaluated microRNAs (miRNAs) as potential biomarkers for Alzheimer disease (AD) by analyzing the expression level of miRNAs in CSF of patients with AD dementia and nonaffected control subjects. METHODS: Using quantitative PCR, we profiled the expression level of 728 miRNAs in CSF of nonaffected control subjects and patients with clinically ascertained AD dementia, and we further compared the expression level of candidate miRNAs in 37 control subjects and 35 patients with AD dementia. RESULTS: The level of hsa-miR-27a-3p in CSF is reduced in patients with dementia due to AD in 2 different cohorts of subjects (cohort 1: p = 0.008; cohort 2: p = 0.015; 2-tailed unpaired Welch t test). Moreover, low levels of hsa-miR-27a-3p were accompanied by high CSF tau levels and low CSF beta amyloid levels. CONCLUSIONS: Our pilot study highlights hsa-miR-27a-3p as a candidate biomarker for AD and provides the groundwork for further confirmation studies in larger cohorts and in other hospitals. PMID- 24212399 TI - A coupled mechano-biochemical model for bone adaptation. AB - Bone remodelling is a fundamental biological process that controls bone microrepair, adaptation to environmental loads and calcium regulation among other important processes. It is not surprising that bone remodelling has been subject of intensive both experimental and theoretical research. In particular, many mathematical models have been developed in the last decades focusing in particular aspects of this complicated phenomenon where mechanics, biochemistry and cell processes strongly interact. In this paper, we present a new model that combines most of these essential aspects in bone remodelling with especial focus on the effect of the mechanical environment into the biochemical control of bone adaptation mainly associated to the well known RANKL-RANK-OPG pathway. The predicted results show a good correspondence with experimental and clinical findings. For example, our results indicate that trabecular bone is more severely affected both in disuse and disease than cortical bone what has been observed in osteoporotic bones. In future, the methodology proposed would help to new therapeutic strategies following the evolution of bone tissue distribution in osteoporotic patients. PMID- 24212400 TI - Fine-scale distribution of ectomycorrhizal fungi colonizing Tsuga diversifolia seedlings growing on rocks in a subalpine Abies veitchii forest. AB - Numerous species of ectomycorrhizal (ECM) fungi coexist under the forest floor. To explore the mechanisms of coexistence, we investigated the fine-scale distribution of ECM fungal species colonizing root tips in the root system of Tsuga diversifolia seedlings in a subalpine forest. ECM root tips of three seedlings growing on the flat top surface of rocks were sampled after recording their positions in the root system. After the root tips were grouped by terminal restriction fragment length polymorphism (T-RFLP) analysis of ITS rDNA, the fungal species representing each T-RFLP group were identified using DNA sequencing. Based on the fungal species identification, the distribution of root tips colonized by each ECM fungus was mapped. Significant clustering of root tips was estimated for each fungal species by comparing actual and randomly simulated distributions. In total, the three seedlings were colonized by 40 ECM fungal species. The composition of colonizing fungal species was quite different among the seedlings. Twelve of the 15 major ECM fungal species clustered significantly within a few centimeters. Some clusters overlapped or intermingled, while others were unique. Areas with high fungal species diversity were also identified in the root system. In this report, the mechanisms underlying generation of these ECM root tip clusters in the root system are discussed. PMID- 24212401 TI - Colonoscopy as a tool for evaluating colorectal tumor development in a mouse model. AB - PURPOSE: A sporadic colon cancer mouse model with conditional mutations in adenomatous polyposis coli (Apc) is biologically relevant for human colorectal cancer (CRC). This study aimed to determine the utility and limitations of colonoscopy for evaluating colon tumors in this mouse model. METHODS: We compared the estimates of location, size, and miss rate of tumors detected during colonoscopy with those determined by necropsy. Sixty-six CPC-Apc mice originating from Apc (F/wt) mice harbor a Cdx2-Cre transgene in which colorectal tumorigenesis was driven by Apc allelic loss. The sensitivity and specificity of colonoscopy for detecting tumors in a mouse CRC model were investigated. RESULTS: A strong positive correlation was found between tumor location as measured by colonoscopy and the location determined by necropsy (p < 0.001). A total of 120 tumors were graded during colonoscopy (grades 1-5: 0, 8, 20, 27, and 65 lesions, respectively), and a strong positive correlation was found between the tumor grade determined by colonoscopy and size measured by necropsy (grades 2-5: 2.08, 2.98, 4.02, and 5.09 mm, respectively; p < 0.005). Although the miss rate was 47.1 %, most of the missed tumors (96 %) were in close proximity (within 5 mm) of another tumor. CONCLUSIONS: A colonoscopic method for the reliable measurement of colorectal tumors in vivo has been established. The application of this technique to mouse models of colon carcinogenesis will provide a better understanding of the dynamics of tumor growth. PMID- 24212402 TI - Molecular phylogeny and genetic variation in the genus Lilium native to China based on the internal transcribed spacer sequences of nuclear ribosomal DNA. AB - We present a comprehensive phylogeny derived from nuclear ribosomal DNA (nrDNA) for 214 samples representing 98 species and five varieties, including 44 species and five varieties native to China. Our collection of 25 species and five varieties (44 samples) covering all five sections of the genus (Comber) distributed in China also were included in the internal transcribed spacer (ITS) database. This study incorporates previous research with an emphasis on Chinese species, including the controversial subsection, Sinomartagon 5c Comber. In the phylogenetic tree obtained by maximum parsimony (PAUP) and maximum likelihood (RAxML) analyses, the samples were divided into four major groups. Our results suggest that the subsection (subsect.) 5c Comber should be classified into the true subsect. 5c and the section (sect.) Lophophorum. And the latter was divided into three subsections (subsect. Lophophorum I, subsect. Lophophorum II, and subsect. Lophophorum III). Based on molecular phylogenetic analysis and fluorescence in situ hybridization, we report that L. henryi and L. rosthornii are closely related, and we propose their classification into subsect. Leucolirion 6a. Our results support Comber's subdivision of sect. Leucolirion, which was primarily based on bulb color. Chinese species were divided into five sections: sect. Martagon, sect. Archelirion, sect. Leucolirion, sect. Sinomartagon, and sect. Lophophorum. These findings contribute to our understanding of the phylogeny, origin, and classification of Lilium. PMID- 24212404 TI - Systems biology of human atherosclerosis. AB - Systems biology describes a holistic and integrative approach to understand physiology and pathology. The "omic" disciplines include genomics, transcriptomics, proteomics, and metabolic profiling (metabonomics and metabolomics). By adopting a stance, which is opposing (yet complimentary) to conventional research techniques, systems biology offers an overview by assessing the "net" biological effect imposed by a disease or nondisease state. There are a number of different organizational levels to be understood, from DNA to protein, metabolites, cells, organs and organisms, even beyond this to an organism's context. Systems biology relies on the existence of "nodes" and "edges." Nodes are the constituent part of the system being studied (eg, proteins in the proteome), while the edges are the way these constituents interact. In future, it will be increasingly important to collaborate, collating data from multiple studies to improve data sets, making them freely available and undertaking integrative analyses. PMID- 24212403 TI - C1q tumor necrosis factor-related protein-3 protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis through the phosphoinositide 3-kinase/Akt pathway. AB - Bone marrow (BM)-derived mesenchymal stem cells (MSCs) represent the leading candidate cell for tissue regeneration in the ischemic myocardium. However, the poor survival of stem cells transplanted into the ischemic myocardium presents a major obstacle in stem cell-based therapy. C1q tumor necrosis factor-related protein 3 (CTRP3) is a newly identified adipokine, similar to adiponectin, with beneficial effects on metabolic regulation. It has been shown to enhance the survival of cardiomyocytes during ischemia, while its expression is reduced following ischemia. In the present study, we examined the hypothesis that CTRP3 may enhance the survival of MSCs during exposure to hypoxia/serum deprivation (SD), and attempted to elucidate the underlying mechanisms. MSCs were obtained from rat bone marrow and cultured. Apoptosis was induced by hypoxia/SD for up to 24 h and the apoptotic rates were assessed by flow cytometry. MSC proliferation was measured using a Cell Counting kit-8 assay. The expression levels of Akt, Bcl 2, Bax, cytochrome c and cleaved caspase-3 were detected by western blot analysis. Mitochondrial membrane potential was examined using a membrane permeable dye. CTRP3 significantly reduced hypoxia/SD-induced apoptosis in a concentration-dependent manner. The hypoxia/SD-induced decrease in the Bcl-2/Bax ratio and the mitochondrial membrane potential, and the increase in cytochrome c and caspase-3 levels were largely reversed by CTRP3. The anti-apoptotic effects of CTRP3 were blocked by inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway with the PI3K inhibitor, LY294002. In conclusion, CTRP3 is a novel anti-apoptotic adipokine that protects MSCs from hypoxia/SD induced apoptosis through the PI3K/Akt signaling pathway. PMID- 24212405 TI - Extracranial internal carotid artery pseudoaneurysm associated with neurofibromatosis type 1 treated with endovascular stenting and coil embolization. AB - An internal carotid artery (ICA) pseudoaneurysm associated with neurofibromatosis type 1 (NF-1) is rare. We report the first case of unruptured extracranial pseudoaneurysm of the ICA in a patient with NF-1 successfully treated with endovascular stenting and coil embolization.A 66-year-old woman diagnosed with NF 1 had sudden left neck pain and massive swelling 3 years earlier. Radiological examination showed a ruptured pseudoaneurysm of the left internal thoracic artery (ITA). The posttreatment computed tomography (CT) scan revealed complete obliteration of the aneurysm of the left ITA and an unruptured pseudoaneurysm of the right ICA. After 3 years of follow-up, a CT scan revealed the enlargement of the pseudoaneurysm of the right extracranial ICA. Endovascular stenting and coil embolization were performed to prevent rupture, and the lesion was completely obliterated. Follow-up angiography at 6 months revealed good flow of the ICA through the stent without any filling of the aneurysm. PMID- 24212406 TI - Neck-targeted, stand-alone coiling for successful treatment of type 1A endoleak following endovascular repair. AB - Endovascular repair is a standard of treatment for patients with abdominal aortic aneurysm who are unfit for open surgery. Type 1A endoleak (T1A-E) is defined as persistent blood flow outside the lumen of the endograft due to a failure of the graft to seal the proximal landing zone adequately. Accordingly, T1A-E treatment is mandatory, and endovascular options, when possible, consist of standard adjuncts as cuffs and stents or sometimes mere ballooning. Alternatively, different embolization techniques have been described in little or case series. We describe a successful management of large T1A-E with solely coil embolization of the isolated leakage area. PMID- 24212407 TI - Systematic review and meta-analysis of balloon angioplasty versus primary stenting in the infrapopliteal disease. AB - OBJECTIVES: We performed a systematic review and meta-analysis of comparing balloon angioplasty and primary stenting for symptomatic infrapopliteal disease to evaluate the clinical value of primary stenting in treating infrapopliteal diseases. METHODS: Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines were followed. PubMed (1984-present), ScienceDirect (1980-present), Embase (1990-present), and CBM (1988-present) databases were searched for relevant articles. Finally, 16 studies (published between 2001 and 2013) satisfying the inclusion criteria were identified. The outcome parameters were immediate technical success, 1-year primary patency rate, 1-year limb salvage rate, and 1-year target vessel revascularization (TVR)-free rate. Comparisons were made with balloon angioplasty and primary stenting, and based on the different types of stents, we divided the primary stent group into the bare metal stent (BMS) group and drug-eluting stent (DES) group. RESULTS: A total of 3789 patients and 4339 limbs constituted our final study population. The technical success rate of balloon angioplasty was 92.29% (95% confidence interval [CI] 88.75%-94.78%). Only 2 study reported the technical failure rates as 4% and 5.2% in the primary stent group. The pooled estimates of 1-year primary patency and TVR-free rate were similarly low in the balloon angioplasty group and BMS group (primary patency: 57.65%, 95% CI 53.54%-61.67% vs 60.95%, 95% CI 48.31% 72.28%, P = .38; TVR-free rate: 73.41%, 95% CI 66.51%-80.08% vs 73.66%, 95% CI 63.58%-81.75%, P = .91). The pooled estimates of 1-year primary patency and TVR free rate in DES group were 81.10% (95% CI 75.48%-85.67%) and 90.30% (95% CI 85.30%-93.73%), respectively, which were better than those of the BMS and balloon angioplasty groups (P < .001 for both). The pooled estimate of 1-year limb salvage in the balloon angioplasty, BMS, and DES groups was 88.61% (95% CI 85.01% 91.43%), 94.41% (95% CI 89.52%-97.1%), and 95.20% (95% CI 86.97%-98.33%), respectively (P < .001). The BMS and DES groups had higher limb salvage rates than the balloon angioplasty group (P < .001 for both comparisons). The rates of severe complications were low both in the balloon angioplasty and in the primary stent groups. CONCLUSION: Primary BMS implantation had no advantage over balloon angioplasty in reducing restenosis or revascularization for infrapopliteal disease. Primary DES implantation seems to be a promising treatment for focal infrapopliteal lesions. Publication bias could not be ruled out, and the results should be treated with caution. PMID- 24212408 TI - Racial/ethnic disparities in amputation and revascularization: a nationwide inpatient sample study. AB - This study investigates whether ethnic minorities presenting with critical limb ischemia (CLI) are more likely to undergo major limb amputation compared to white patients. The Nationwide Inpatient Sample (NIS) database was used to identify all patients admitted with CLI; lower extremity revascularization; and major lower extremity amputation from 1998 to 2005. The NIS identified 240 139 patients presenting with CLI--68.2% white, 19.5% black, 9.0% Hispanic, and 1.24% Asian. In all, 83 328 patients underwent revascularization--73.7% white, 15.9% black, 7.4% Hispanic, and 1.1% Asian. The majority of the interventions were open. In all, 111 548 patients underwent a major lower extremity amputation--61% white, 25.4% black, 10.1% Hispanic, and 1.1% Asian. The mean Charlson comorbidity scores for amputation were 2.1 for whites, 2.0 for blacks, 2.3 for Hispanics, and 2.5 for Asians (for all data, P < .05). Blacks make up a disproportionately higher proportion of patients admitted for CLI and undergoing amputation, with a lower proportion undergoing revascularization. PMID- 24212409 TI - Combination of light and energy-based technologies with topical drug delivery. PMID- 24212410 TI - Excel V roundtable. PMID- 24212411 TI - Put your best foot forward: advances in the management of tinea pedis. PMID- 24212412 TI - Aspects related to a periodontal home prevention program for disabled patients: a clinical trial. AB - AIM: The aim of the present study was to highlight the relationship between the level of oral hygiene and the context in which the patient receives dental treatment, demonstrating that home service is essential and effective to decrease the incidence of periodontal diseases. METHODS: The study was initially conducted on a heterogeneous sample of patients including 48 individuals with psycho-motor deficits. The study included 28 males (58.3%) and 20 females (41.7%) aged between 18 and 50 years, coming from two different sites ("Fa.Di.Vi... e oltre" and "Dentistry Unit, Istituto G. Gaslini" in Genoa). The patients were evaluated during the period 2008-2009. After this first pilot study, a clinical trial was conducted within the educational center "Il Granello", with the participation of 20 patients with disabilities. RESULTS: This study demonstrates that home assistance is essential and effective to decrease the incidence of those periodontal diseases induced by bacterial dental plaque accumulation, and associated with aggravating factors like the repeated use of drugs, such as benzodiazepines, phenylhydantoin, and cyclosporin A, that cause gingival hypertrophia. CONCLUSION: This study was proposed to demonstrate that the availability of a dental service within institutions could improve not only the dental-periodontal conditions of the participants, but also decrease the admission of these subjects to hospitals, contributing to the reduction of public expenditure by the Health Care System. PMID- 24212413 TI - Observation of growth of metal nanoparticles. AB - An understanding of nanocrystal growth mechanisms is of significant importance for the design of novel materials. The development of liquid cells for transmission electron microscopy (TEM) has enabled direct observation of nanoparticle growth in a liquid phase. By tracking single particle growth trajectories with high spatial resolution, novel growth mechanisms have been revealed. In recent years, there has been an increasing interest in liquid cell TEM and its applications include real time imaging of nanoparticles, biological materials, liquids, and so on. This paper reviews the development of liquid cell TEM and the progress made in using such a wonderful tool to study the growth of nanoparticles (mostly metal nanoparticles). Achievements in the understanding of coalescence, shape control mechanisms, surfactant effects, etc. are highlighted. Other studies relevant to metal precipitation in liquids, such as electrochemical deposition, nanoparticle motion and electron beam effects, are also included. At the end, our perspectives on future challenges and opportunities in liquid cell TEM are provided. PMID- 24212414 TI - Hourglass epidermoid inclusion cyst of the hand. PMID- 24212415 TI - Bilateral terminal absence of the thumbs. PMID- 24212416 TI - Contralateral lower trapezius transfer for restoration of shoulder external rotation in traumatic brachial plexus palsy: a preliminary report and literature review. AB - The importance of external rotation of the shoulder is well accepted. Patients with inadequate recovery of shoulder function after nerve transfers for a brachial plexus injury have difficulty in using their reconstructed limb. The options for secondary procedures to improve shoulder function are often limited, especially if the spinal accessory nerve has been used earlier for nerve transfer or as a donor nerve for a free functioning muscle transfer. We have used the contralateral lower trapezius transfer to the infraspinatus in three cases, to restore shoulder external rotation. All patients had significant improvement in shoulder external rotation (mean 97 degrees ; range 80 degrees -110 degrees ) and improved disability of the arm, shoulder and hand scores. The rotation occurred mainly at the glenohumeral joint, and was independent of the donor side. All patients were greatly satisfied with the outcome. Contralateral lower trapezius transfer appears to help in overall improvement of shoulder function by stabilizing the scapula. The results have remained stable after mean follow-up of 58 months (range 12-86). No donor site deficit was seen in any patient. PMID- 24212417 TI - [Current therapy of neuropathic pain]. AB - Lesions of the nervous systems often result in difficult to treat pain syndromes. Neuropathic pain has increasingly gained attention from clinicians as a result of a better understanding of the underlying mechanisms and the development of proven analgesic therapies. This article provides an update on the diagnosis and treatment of neuropathic pain. PMID- 24212418 TI - [Update on trigeminal autonomic cephalalgia]. AB - Cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are classified under trigeminal autonomic cephalalgia (TAC). The proposed revision of the international classification of headache disorders (ICDH-3 beta) adds hemicrania continua to this diagnostic group. Moreover, diagnostic criteria of the other TACs were modified and are characterized by persistent headache or headache attacks accompanied by cranial autonomic symptoms. The main difference between the various TACs is the duration of attacks. Differentiation is important because different pharmacological strategies are necessary. PMID- 24212419 TI - [Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. AB - BACKGROUND: Vagus nerve stimulation (VNS) is one of the numerous stimulation procedures used in the treatment of neurological diseases in which there has been growing interest in recent years. Since 1988 it has been frequently used in the therapy of epilepsies but the mechanism of action is still unknown. It is considered to be low in adverse effects. TOPICS: Decision-making process on VNS therapy as well as long-term outcome and adverse effects. METHOD: Retrospective analysis of all 62 patients treated over a long period by VNS in the Epilepsy Center of the University Hospital of Freiburg (Germany) from 1 August 2002 through 4 January 2011. RESULTS: OUTCOME: the results show that 2 out of 62 patients became seizure-free under VNS therapy while maintaining the already existing anti-ictal medication and 4 more patients under VNS plus dosage increase of the already existing medication and/or new medication. However, in 34 out of 62 patients VNS therapy did not improve the seizure situation. Adverse effects: VNS is not as low in adverse effects as is generally considered. Only 9 out of 62 patients did not show any adverse effects and on the other hand severe, even life threatening adverse effects also occurred. CONCLUSION: Patients undergoing VNS therapy have to be carefully checked for possible adverse effects, not only at the beginning of VNS therapy but also in the long-term course. These results have to be considered in the cost-benefit analysis of this treatment. PMID- 24212420 TI - Osmotic responses of maize roots : Water and solute relations. AB - Water and solute relations of excised seminal roots of young maize (Zea mays L) plants, have been measured using the root pressure probe. Upon addition of osmotic solutes to the root medium, biphasic root pressure relaxations were obtained as theoretically expected. The relaxations yielded the hydraulic conductivity Lp r) the permeability coefficient (P sr), and the reflection coefficient (sigma sr) of the root. Values of Lp r in these experiments were by nearly an order of magnitude smaller than Lp r values obtained from experiments where hydrostatic pressure gradients were used to induce water flows. The value of P sr was determined for nine different osmotica (electrolytes and nonelectrolytes) which resulted in rather variable values (0.1.10(-8)-1.7.10( 8)m.s(-1)). The reflection coefficient sigma sr of the same solutes ranged between 0.3 and 0.6, i.e. sigma sr was low even for solutes for which cell membranes exhibit a sigma s~1. Deviations from the theoretically expected biphasic responses occured which may have reflected changes of either P sr or of active pumping induced by the osmotic change. The absolute values of Lp r, P sr, and sigma sr have been critically examined for an underestimation by unstirred layer effecs. The data indicate a considerable apoplasmic component for radial movement of water in the presence of hydrostatic gradients and also some solute flow byppassing root protoplasts. In the presence of osmotic gradients, however, there was a substantial cell-to-cell transport of water. Cutting experiments demonstrated that the hydraulic resistance for the longitudinal movement of water was much smaller than for radial transport except for the apical ends of the segments (length=5 to 20 mm). The differences in Lp r as well as the low sigma sr values suggest that the simple osmometer model of the root with a single osmotic barrier exhibiting nearly semipermeable properties should be extended for a composite membrane model with hydraulic and osmotic barriers arranged in series and in parallel. PMID- 24212421 TI - Tissue slices from living root caps as a model system in which to study cytodifferentiation of polar cells. AB - Tissue slices of living root caps of cress (Lepidium sativum L.), two to three cell layers in thickness, were prepared by a microsurgical procedure. The viability, cellular structures and cytoplasmic movement of the cells were examined in the light microscope. Nuclei, amyloplasts, vacuoles and endoplasmic reticulum were identified and their positions confirmed after fixation and observation of the same cells in the electron microscope. The distribution of microtubules was shown by immunocytochemistry. During germination, microtubules appear first at the distal edges of the statocytes, while in mature statocytes a distal domain of criss-crossed microtubules could be distinguished from a proximal domain with transversally oriented microtubules. Microfilaments in young statocytes form a nuclear enclosure; in mature statocytes bundles of microfilaments fan out into the cell cortex. The transition from statocytes to secretion cells is accompanied by a more pronounced cortical network of microfilaments, while the nucleus-associated microfilaments remain visible. It is suggested that these microfilaments play a role in the positioning of the nucleus and the translocation of endoplasmic reticulum. PMID- 24212422 TI - Heterogeneity of auxin-accumulating membrane vesicles from Cucurbita and Zea: a possible reflection of cell polarity. AB - When microsomes from hypocotyls of Cucurbita pepo L. or coleoptiles of Zea mays L. were centrifuged on dextran-sucrose gradients a heterogeneity of auxin accumulating vesicles was observed. Vesicles from the top part of the gradient showed saturable, specific accumulation of indole-3-acetic acid with only a small stimulation by phytotropins, and with very few binding sites for 1-N naphthylphthalamic acid. In the vesicles from the lower part of the gradient, net accumulation of indole-3-acetic acid could be strongly increased by addition of phytotropins; binding of 1-N-naphthylphthalamic acid was high in this region. After two-phase partitioning, both kinds of vesicles were found in the upper phase membrane fraction considered to be purified plasma membrane. The hypothesis is discussed that vesicles can be separated from the apical and basal parts of the cell's plasmalemma. PMID- 24212423 TI - Leaf and canopy responses of Lolium perenne to long-term elevated atmospheric carbon-dioxide concentration. AB - The relationship between leaf photosynthetic capacity (p n, max), net canopy CO2- and H2O-exchange rate (NCER and E t, respectively) and canopy dry-matter production was examined in Lollium perenne L. cv. Vigor in ambient (363+/-30 MUl. l(-1)) and elevated (631+/-43 MUl.l(-1)) CO2 concentrations. An open system for continuous and simultaneous regulation of atmospheric CO2 concentration and NCER and E t measurement was designed and used over an entire growth cycle to calculate a carbon and a water balance. While NCERmax of full-grown canopies was 49% higher at elevated CO2 level, stimulation of p n, max was only 46% (in spite of a 50% rise in one-sided stomatal resistance for water-vapour diffusion), clearly indicating the effect of a higher leaf-area index under high CO2 (approx. 10% in one growing period examined). A larger amount of CO2-deficient leaves resulted in higher canopy dark-respiration rates and higher canopy light compensation points. The structural component of the high-CO2 effect was therefore a disadvantage at low irradiance, but a far greater benefit at high irradiance. Higher canopy darkrespiration rates under elevated CO2 level and low irradiance during the growing period are the primary causes for the increase in dry-matter production (19%) being much lower than expected merely based on the NCERmax difference. While total water use was the same under high and low CO2 levels, water-use efficiency increased 25% on the canopy level and 87% on a leaf basis. In the course of canopy development, allocation towards the root system became greater, while stimulation of shoot dry-matter accumulation was inversely affected. Over an entire growing season the root/shoot production ratio was 22% higher under high CO2 concentration. PMID- 24212424 TI - Aspartic proteinase from wheat seeds: isolation, properties and action on gliadin. AB - Wheat endosperm was shown to contain an aspartic proteinase capable of hydrolyzing the wheat storage protein, gliadin, in vitro. The enzyme was purified to homogeneity by affinity chromatography on bacilliquin-silochrome, diethylaminoethyl-Toyopearl ion-exchange chromatography, chromatofocusing, and preparative polyacrylamide gel electrophoresis. The sedimentation constant of the enzyme was 3.4 S and the relative molecular mass (Mr), determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 58000 dalton (Da). The purified enzyme was completely inhibited by pepstain whereas other enzyme inhibitors did not affect its activity. The enzyme was found to hydrolyze mainly omega- and gamma-gliadins with Mr's of 67000-95000 Da, with maximal activity at pH 4.5. The data make it possible to suggest that the enzyme has an endogenous function by initiating proteolysis of storage proteins in germinating wheat seeds. PMID- 24212425 TI - Sucrose transport into the phloem of Ricinus communis L. seedlings as measured by the analysis of sieve-tube sap. AB - Careful cutting of the hypocotyl of Ricinus communis L. seedlings led to the exudation of pure sieve-tube sap for 2-3 h. This offered the possibility of testing the phloem-loading system qualitatively and quantitatively by incubating the cotyledons with different solutes of various concentrations to determine whether or not these solutes were loaded into the sieve tubes. The concentration which was achieved by loading and the time course could also be documented. This study concentrated on the loading of sucrose because it is the major naturally translocated sieve-tube compound. The sucrose concentration of sieve-tube sap was approx. 300 mM when the cotyledons were buried in the endosperm. When the cotyledons were excised from the endosperm and incubated in buffer, the sucrose concentration decreased gradually to 80-100 mM. This sucrose level was maintained for several hours by starch breakdown. Incubation of the excised cotyledons in sucrose caused the sucrose concentration in the sieve tubes to rise from 80 to 400 mM, depending on the sucrose concentration in the medium. Thus the sucrose concentration in the sieve tubes could be manipulated over a wide range. The transfer of labelled sucrose to the sieve-tube sap took 10 min; full isotope equilibration was finally reached after 2 h. An increase of K(+) in the medium or in the sieve tubes did not change the sucrose concentration in the sievetube sap. Similarly the experimentally induced change of sucrose concentration in the sieve tubes did not affect the K(+) concentration in the exudate. High concentrations of K(+), however, strongly reduced the flow rate of exudation. Similar results were obtained with Na(+) (data not shown). The minimum translocation speed in the sieve tubes in vivo was calculated from the growth increment of the seedling to be 1.03 m.h(-1), a value, which on average was also obtained for the exudation system with the endosperm attached. This comparison of the in-vivo rate of phloem transport and the exudation rate from cut hypocotyls indicates that sink control of phloem transport in the seedlings of that particular age was small, if there was any at all, and that the results from the experimental exudation system were probably not falsified by removal of the sink tissues. PMID- 24212426 TI - Transport of hexoses by the phloem of Ricinus communis L. seedlings. AB - The sieve-tube sap of Ricinus communis L. seedlings has been analysed to determine whether or not hexoses can be taken up by the phloem. Under natural conditions, i.e. with the endosperm attached to the cotyledons, glucose and fructose occurred only in trace amounts in the sieve-tube sap. Incubation of the cotyledons with hexoses in the concentration range 25-200 mM caused a rapid and substantial uptake of hexoses into the phleom, where they appeared eventually in the sieve-tube sap at the same concentration as in the incubation medium. Phloem loading of glucose, 3-O-methyl-glucose and sorbitol occurred easily, whereas fructose was less well loaded. glucose and to a larger extent fructose were also transformed to sucrose, which was loaded into the phloem. The loading of hexoses into the sieve tubes as observed in the experimental exudation system also occurred in the intact seedling, but transloction in the latter soon came to a standstill, probably because of lack of consumption by the sink tissues. These results indicate that the virtual absence of hexoses in the sievetube sap under in-vivo conditions is not because of the inability of the phloem-loading system to transport the monosaccharides but because of the absence of sufficiently high concentrations in the apoplast. PMID- 24212427 TI - The differential transport of amino acids into the phloem of Ricinus communis L. seedlings as shown by the analysis of sieve-tube sap. AB - The cotyledons of castor bean (Ricinus communis L.) act as absorption organs for amino acids, which are supplied to the medium. The analysis of the sieve-tube sap, which exudes from the cut hypocotyl, demonstrated the ability of the cotyledons to load particular amino acids into the phloem and to reject the loading of others. The sieve-tube sap of cotyledons, which were embedded in the endosperm, contained 150 mM amino acids, with 50 mM glutamine as the major amino acid, and 10-15 mM each of valine, isoleucine, lysine and arginine. Removal of the endosperm led to a drastic decline in the amino-acid content of sieve-tube sap down to 16 mM. Addition of single amino acid species to the medium increased the amino acid concentration in the sieve-tube sap in specific manner: glutamine caused the largest increase (up to 140 mM in exudate), glutamate and alanine smaller increases (up to 60 mM), and arginine the smallest. In addition, the amino acid composition of the sieve-tube sap changed, for instance, glutamine or alanine readily appeared in the sieve-tube sap upon incubation in glutamine or alanine, respectively, whereas glutamate was hardly discernible even in the case of incubation with glutamate; arginine was loaded into the sieve tubes only reluctantly. In general, glutamine and alanine accumulated four- to tenfold in the sieve tubes. The uptake of amino acids and of sucrose into the sieve tubes was interdependent: the loading of sucrose strongly reduced the amino acid concentration in the sieve-tube exudate and loading of amino acids decreased the sucrose concentration. Comparison of the concentrations of various amino acids on their way from the endosperm via the cotyledon-endosperm interface, through the cotyledons and into the sieve tubes showed that glutamine, valine, isoleucine and lysine are accumulated on this pathway, whereas glutamate and arginine are more concentrated in the cotyledons than in the sieve tubes. Obviously the phloem loading system has a transport specificity different from that of the amino acid uptake system of the cotyledon in general and it strongly discriminates between amino acids within the cotyledons. PMID- 24212428 TI - The state of the photosynthetic apparatus in leaves as analyzed by rapid gas exchange and optical methods: the pH of the chloroplast stroma and activation of enzymes in vivo. AB - The exchange of CO2 and O2 was measured in leaves using specially constructed equipment capable of responding to rapid transients. Optical measurements provided information on cytochrome f and P 700 oxidation in the light. The following results were obtained: i) The solubilization of CO2 was used to calculate the pH of the chloroplast stroma in darkened leaves. Values ranged from pH 7.8 to pH 8.0 in different C3 plants. ii) Illumination of predarkened leaves of Helianthus annuus L. resulted in three distinct phases of O2 evolution that illustrate the complexity of light activation of the photosynthetic apparatus. A first burst of O2 is attributed to the reduction of electron carriers of the electron-transport chain. While plastoquinone was reduced, cytochrome f was oxidized. Appreciable oxidation of P 700 became possible only during the second O2 burst, which indicates the reduction of the phosphoglycerate pool. Extensive oxidation required the opening of an electron gate on the reducing side of photosystem I. The subsequent slow rise in O2 evolution towards a steady state reflects activation of the Calvin cycle and is the result of CO2 assimilation. iii) Light-dependent CO2 uptake by predarkened leaves occurred in four phases, three of them based on pH changes in the chloroplast stroma. Initial CO2 uptake was small and probably caused by protonation of reduced plastoquinone. In the second phase, which coincided with the reduction of the pool of phosphoglycerate, the initial alkalization of the chloroplast stroma was substantially increased. In the third phase, the stroma alkalization decreased, and the fourth phase was dominated by CO2 assimilation. iv) Respiratory CO2 production was partially suppressed in the light during the second phase of O2 evolution while phosphoglycerate was being reduced. PMID- 24212429 TI - Nitrite reduction and carbohydrate metabolism in plastids purified from roots of Pisum sativum L. AB - Intact preparations of plastids from pea (Pisum sativum L.) roots have been used to investigate the metabolism of glucose-6-phosphate and reduction of inorganic nitrite within these organelles. The ability of hexose-phosphates to support nitrite reduction was dependent on the integrity of the preparation and was barely measurable in broken organelles. In intact plastids, nitrite was reduced most effectively in the presence of glucose-6-phosphate (Glc6P), fructose-6 phosphate and ribose-5-phosphate and to a lesser extent glucose-1-phosphate. The Km (Glc6P) of plastid-located Glc6P dehydrogenase (EC 1.1.1.49) and Glc6P dependent nitrite reduction were virtually identical (0.68 and 0.66 mM respectively) and a similar relationship was observed between fructose-6 phosphate, hexose-phosphate isomerase (EC 5.3.1.9) and nitrite reduction. The pattern of release of CO2 from different carbon atoms of Glc6P supplied to root plastids, indicates the operation of both glycolysis and the oxidative pentose phosphate pathway with some recycling in the latter. During nitrite reduction the evolution of CO2 from carbon atom 1 of Glc6P was stimulated but not from carbon atoms 2, 3, 4, or 6. The importance of these results with regard to the regulation of the pathways of carbohydrate oxidation and nitrogen assimilation within root plastids is discussed. PMID- 24212430 TI - Inhibition of photosynthesis of sunflower leaves by an endogenous solute and interdependence of different photosynthetic reactions. AB - Photosynthesis of Helianthus annuus L. leaves was transiently inhibited and respiration was stimulated when a leaf was detached from the plant by cutting the petiole under water. These effects were caused by a solute which was released by cutting and was transported by the transpiration stream to the leaf blade. This endogenous solute decreased the quantum efficiency of photosynthesis and inhibited reactions of the Calvin cycle. It exerts its effects by uncoupling ATP synthesis from electron transport, thus stimulating respiration and inhibiting photosynthesis. The observation that not only the ATP-dependent reactions of photosynthesis, but also the light-regulated enzymes such as fructose bisphosphatase and ribulose bisphosphate carboxylase were inhibited in the presence of the solute illustrates the complex dependence of Calvin-cycle enzymes on the energization and the redox state of the thylakoid system. Since electron pressure increased during the inhibition of photosynthesis, deactivation of fructose bisphosphatase cannot be explained by effects on the thioredoxin system which is responsible for the light activation of this enzyme. PMID- 24212431 TI - Photochemical efficiency of photosystem II, photon yield of O2 evolution, photosynthetic capacity, and carotenoid composition during the midday depression of net CO2 uptake in Arbutus unedo growing in Portugal. AB - During the "midday depression" of net CO2 exchange in the mediterranean sclerophyllous shrub Arbutus unedo, examined in the field in Portugal during August of 1987, several parameters indicative of photosynthetic competence were strongly and reversibly affected. These were the photochemical efficiency of photosystem (PS) II, measured as the ratio of variable to maximum chlorophyll fluorescence, as well as the photon yield and the capacity of photosynthetic O2 evolution at 10% CO2, of which the apparent photon yield of O2 evolution was most depressed. Furthermore, there was a strong and reversible increase in the content of the carotenoid zeaxanthin in the leaves that occurred at the expense of both violaxanthin and beta-carotene. Diurnal changes in fluorescence characteristics were interpreted to indicate three concurrent effects on the photochemical system. First, an increase in the rate of radiationless energy dissipation in the antenna chlorophyll, reflected by changes in 77K fluorescence of PSII and PSI as well as in chlorophyll a fluorescence at ambient temperature. Second, a state shift characterized by an increase in the proportion of energy distributed to PSI as reflected by changes in PSI fluorescence. Third, an effect lowering the photon yield of O2 evolution and PSII fluorescence at ambient temperature without affecting PSII fluorescence at 77K which would be expected from a decrease in the activity of the water splitting enzyme system, i.e. a donor side limitation. PMID- 24212432 TI - Involvement of polyamines in the inhibiting effect of injury caused by cutting on K(+) uptake through the plasma membrane. AB - The inhibition of K(+) uptake through the plasma membrane resulting from injury caused by cutting, or from application of polyamines (PAs), has been investigated in root segments of maize (Zea mays L.) and pea (Pisum sativum L.). It was found, for both treatments, that K(+) uptake recovered if the segments were washed for 2 h. The K(+) uptake inhibited by cutting and that inhibited by spermidine treatment were stimulated to the same extent by fusicoccin. In addition, there was a correlation between the extent of the recovery of K(+) uptake caused by washing and the distribution, along the root axis, of both PAs and the activities of enzymes responsible for PA degradation. In apical segments of maize, where the PA content and the activity of the degradative enzyme polyamine oxidase (EC 1.5.3.3) were higher than in the more distal segments, the recovery of K(+) uptake caused by washing was also higher. On the other hand, the opposite trend was observed in root segments of pea, where the PA content and the activity of the degradative enzyme diamine oxidase (EC 1.4.3.6) were higher in distal segments in which K(+) uptake was greatly stimulated by washing. The effect of the amine-oxidase inhibitor, aminoguanidine, indicates that the degradation products of PAs are involved in the mechanism of inhibition of K(+) uptake by PAs. The data also seem to indicate that PAs and their degradation products are responsible for the inhibition of K(+) uptake occurring as a result of injury sustained by cutting roots into segments. PMID- 24212433 TI - Adenylate effects on protein phosphorylation in the interenvelope lumen of pea chloroplasts. AB - A 64-kilodalton (kDa) protein, situated in the lumen between the inner and outer envelopes of pea (Pisum sativum L.) chloroplasts (Soll and Bennett 1988, Eur. J. Biochem., 175, 301-307) is shown to undergo reversible phosphorylation in isolated mixed envelope vesicles. It is the most conspicuously labelled protein after incubation of envelopes with 33 nmol.1(-1) [gamma-(32)P]ATP whereas incubation with 50 MUmol.1(-1) [gamma-(32)P]ATP labels most prominently two outer envelope proteins (86 and 23 kDa). Half-maximum velocity for phosphorylation of the 64-kDa protein occurs with 200 nmol.1(-1) ATP, and around 40 MUmol.1(-1) ATP for phosphorylation of the 86- and 23-kDa proteins, indicating the operation of two distinct kinases. GGuanosine-, uridine-, cytidine 5'-triphosphate and AMP are poor inhibitors of the labelling of the 64-kDa protein with [gamma-(32)P]ATP. On the other hand, ADP has a potent influence on the extent of labelling (half maximal inhibition at 1-5 MUmol.1(-1)). The ADP-dependent appearance of (32)P in ATP indicates that ADP acts by reversal of kinase activity and not as a competitive inhibitor. However, the most rapid loss of (32)P from pre-labelled 64 kDa protein occurs when envelope vesicles are incubated with ATP t1/2=15 s at 20 MUmolsd1(-1) ATP). This induced turnover of phosphate appears to be responsible for the rapid phosphoryl turnover seen in situ. PMID- 24212434 TI - Control of the circadian rhythm of carbon dioxide assimilation in Bryophyllum leaves by exposure to darkness and high carbon dioxide concentrations. AB - The circadian rhythm of CO2 assimilation in detached leaves of Bryophyllum fedtschenkoi at 15 degrees C in normal air and continuous illumination is inhibited both by exposure to darkness, and to an atmosphere enriched with 5% CO2. During such exposures substantial fixation of CO2 takes place, and the malate concentration in the cell sap increases from about 20 mM to a constant value of 40-50 mM after 16 h. On transferring the darkened leaves to light, and those exposed to 5% CO2 to normal air, a circadian rhythm of CO2 assimilation begins again. The phase of this rhythm is determined by the time the transfer is made since the first peak occurs about 24 h afterwards. This finding indicates that the circadian oscillator is driven to, and held at, an identical, fixed phase point in its cycle after 16 h exposure to darkness or to 5% CO2, and it is from this phase point that oscillation begins after the inhibiting condition is removed. This fixed phase point is characterised by the leaves having acquired a high malate content. The rhythm therefore begins with a period of malate decarboxylation which lasts for about 8 h, during which time the malate content of the leaf cells must be reduced to a value that allows phosphoenolpyruvate carboxylase to become active. Inhibition of the rhythm in darkness, and on exposure to 5% CO2 in continuous illumination, appears to be due to the presence of a high concentration of CO2 within the leaf inhibiting malic enzyme which leads to the accumulation of high concentrations of malate in the leaf cells. The malate then allosterically inhibits phosphoenolpyruvate carboxylase upon which the rhythm depends. The results give support to the view that malate synthesis and breakdown form an integral part of the circadian oscillator in this tissue. PMID- 24212435 TI - Photoinhibition at chilling temperature : Fluorescence characteristics of unhardened and cold-acclimated spinach leaves. AB - The effects of moderate light at chilling temperature on the photosynthesis of unhardened (acclimated to +18 degrees C) and hardened (cold-acclimated) spinach (Spinacea oleracea L.) leaves were studied by means of fluorescence-induction measurements at 20 degrees C and 77K and by determination of quantum yield of O2 evolution. Exposure to 550 MUmol photons.m(-2).s(-1) at +4 degrees C induced a strong photoinhibition in the unhardened leaves within a few hours. Photoinhibition manifested by a decline in quantum yield was characterized by an increase in initial fluorescence (F o) and a decrease in variable fluorescence (F v) and in the ratio of variable to maximum fluorescence (F V/F M), both at 77K and 20 degrees C. The decline in quantum yield was more closely related to the decrease in the F V/F M ratio measured at 20 degrees C, as compared with F V/F M at 77K. Quenching of the variable fluorescence of photosystem II was accompanied by a decline in photosystem-I fluorescence at 77K, indicating increased thermal de-excitation of pigments as the main consequence of the light treatment. All these changes detected in fluorescence parameters as well as in the quantum yield of O2 evolution were fully reversible within 1-3 h at a higher temperature in low light. The fast recovery led us to the view that this photoinhibition represents a regulatory mechanism protecting the photosynthetic apparatus from the adverse effects of excess light by increasing thermal energy dissipation. Long-term cold acclimation probably enforces other protective mechanisms, as the hardened leaves were insensitive to the same light treatment that induced strong inhibition of photosynthesis in unhardened leaves. PMID- 24212436 TI - Comparison of acetate- and pyruvate-dependent fatty-acid synthesis by spinach chloroplasts. AB - In recent studies using intact chloroplasts of spinach (Spinacia oleracea L.) to investigate the accumulation of acetyl-CoA produced by the activity of either acetyl-CoA synthetase (EC 6.2.1.1) or the pyruvate-dehydrogenase complex, this product was not detectable. These results in combination with new information on the physiological levels of acetate and pyruvate in spinach chloroplasts (H.-J. Treede et al. 1986, Z. Naturforsch. 41 C, 733-740) prompted a reinvestigation of the incorporation of [1-(14)C] acetate and [2-(14)C] pyruvate into fatty acids at physiological concentrations.The K m for the incorporation into fatty acids was about 0.1 mM for both metabolites and thus agreed with the values obtained by H. J. Treede et al. (1986) for acetyl-CoA synthetase and the pyruvate dehydrogenase complex. However, acetate was incorporated with a threefold higher V max. Saturation for pyruvate incorporation into the fattyacid fraction was achieved only at physiological pyruvate concentrations (<1.0 mM). The diffusion kinetics observed at higher concentrations may be the result of contamination with derivates of the labeled substrate. Competition as well as double-labeling experiments with [(3)H]acetate and [2-(14)C]pyruvate support the notion that, at least in spinach, chloroplastic acetate is the preferred substrate for fatty-acid synthesis when both substrates are supplied concurrently (P.G. Roughan et al., 1979 b, Biochem. J. 184, 565-569).Experiments with spinach leaf discs confirmed the predominance of fatty-acid incorporation from acetate. Radioactivity from [1 (14)C]acetate appeared to accumulate in glycerolipids while that from [2 (14)C]pyruvate was apparently shifted in favor of the products of prenyl metabolism. PMID- 24212437 TI - The rheology, microstructure and sensory characteristics of a gluten-free bread formulation enhanced with orange pomace. AB - The present manuscript studied a previously optimised gluten-free bread formulation containing 5.5% orange pomace (OP) in relation to the batter characteristics (i.e. pre-baking), microstructure (of the flours, batter and bread) and sensory characteristics of the bread. Rheology, RVA and mixolab results illustrated that orange pomace improved the robustness of the gluten-free batter and decreased the occurrence of starch gelatinisation. This was confirmed from the confocal laser scanning microscopy (CLSM) images, which showed potato starch granules to be more expanded in the control batter when compared to the sample containing orange pomace. Starch granules were also observed to be more enlarged and swollen in the CLSM bread images, suggesting a higher level of gelatinisation occurred in the control sample. Sensory analysis was carried out on the optimised and control bread; panellists scored the flavour, crumb appearance and overall acceptability of the OP-containing breads comparable to the control. PMID- 24212438 TI - A core-shell-satellite structured Fe3O4@MS-NH2@Pd nanocomposite: a magnetically recyclable multifunctional catalyst for one-pot multistep cascade reaction sequences. AB - A hierarchical core-shell-satellite structured composite system Fe3O4@MS-NH2@Pd, which was composed of Pd nanoparticles well-dispersed on an amino group functionalized mesoporous silica (MS-NH2) nanosphere, and superparamagnetic Fe3O4 nanoparticles scattered inside the silica sphere, was prepared by using a facile procedure. The composite combined the catalytic properties of amino groups and Pd nanoparticles with superparamagnetic properties of magnetite into a single platform. This integrated nanosystem acted as an efficient magnetically recyclable noble metal-base multifunctional nanocatalyst and showed excellent catalytic activity, selectivity and stability for the direct synthesis of alpha alkylated nitriles under mild conditions through facile one-pot multistep cascade reaction sequences. PMID- 24212439 TI - Influence of time delay on the estimated lung shunt fraction on 99mTc-labeled MAA scintigraphy for 90Y microsphere treatment planning. AB - 90Y-microspheres therapy is used to treat selected patients with primary or metastatic liver tumors in a safe and effective way. As a preparation for 90Y microspheres treatment, a 99mTc-macroaggregated albumin (99mTc-MAA) simulation procedure is essential to evaluate particle shunting to the lung or gastrointestinal tract. We investigated the effect of interval between injection of 99mTc-MAA and time of scanning on the lung shunt fraction (LSF). In 4 patients with secondary hepatic malignancies who underwent repeated whole-body scintigraphy up to 5 hours after injection of 99mTc-MAA, a marked change in LSF was observed. It appears that tracer degradation leads to an important overestimation of LSF at later time points. An overestimation of LSF can lead to dose reduction or canceling of the planned 90Y-microspheres treatment. It is concluded that the interval between injection and scanning should be kept as short as possible. PMID- 24212440 TI - Metabolic imaging of deep brain stimulation in anorexia nervosa: a 18F-FDG PET/CT study. AB - OBJECTIVES: Anorexia nervosa (AN), a disorder of unknown etiology, has the highest mortality rate of any psychiatric disorder. Drawing the brain metabolic pattern of AN may help to target the core biological and psychological features of the disorder and to perfect the diagnosis and recovery criteria. In this study, we used 18F-FDG PET to show brain metabolic network for AN. METHODS: Glucose metabolism in 6 AN patients and 12 age-matched healthy controls was studied using 18F-FDG PET. SPM2 was used to compare brain metabolism in AN patients with that in healthy controls. Four of 6 AN patients took deep brain stimulation (DBS) targeted in nucleus accumbens (NAcc). About 3 to 6 months after the surgery, the 4 AN patients took another 18F-FDG PET scan to assess the change in brain glucose metabolism. RESULTS: The SPM (statistical parametric mapping ) analysis showed hypermetabolism in the frontal lobe (bilateral, BA10, BA11, BA47), the limbic lobe (bilateral, hippocampus, and amygdala), lentiform nucleus (bilateral), left insula (BA13), and left subcallosal gyrus (BA25). It also showed hypometabolism in the parietal lobe (bilateral, BA7, BA40). The hypermetabolism in frontal lobe, hippocampus, and lentiform nucleus decreased after NAcc-DBS. CONCLUSIONS: The changes in brain glucose metabolism illustrated the brain metabolic pattern in AN patients. Furthermore, the pattern can be modulated by NAcc-DBS, which confirmed specificity of the pattern. The regions with altered metabolism could interconnect to form a network and integrate information related to appetite. Our study may provide information for targeting the potential candidate brain regions for understanding the pathophysiology of AN and assessing the effects of existing and future treatment approaches. PMID- 24212442 TI - Incidental finding of the nutcracker phenomenon detected by 18F-FDGPET/CT. PMID- 24212441 TI - Targeted alpha-particle therapy of bone metastases in prostate cancer. AB - Medical oncology is moving toward personalized and precision treatments. This evolution is spearheaded by ongoing discoveries on the fundamental machinery that controls tumor and hosts microenvironment biological behavior. alpha-Particles with their high energy and short range had long been recognized as potentially useful in the treatment of cancer. More than a century after the discovery of radium by the Curies, 223Ra dichloride is now available in the expanding armamentarium of therapies for metastatic castration-resistant prostate cancer. This advance occurs in the context of several other novel therapeutics in advanced prostate cancer that include more effective androgen receptor pathway inhibition, better chemotherapy, and immunotherapy. We present a concise review on the therapeutic use of 223Ra dichloride in this clinically important setting including excerpts on the radium history, physical properties, the alpharadin in symptomatic prostate cancer clinical trial, and practical information on its use in the clinic. It is anticipated that, with the current emergence of 223Ra as a viable form of therapy, interest in and use of alpha-particle therapy in the management of cancer will grow. PMID- 24212443 TI - Somatostatin receptor molecular imaging for metastatic intracranial hemangiopericytoma. AB - Intracranial hemangiopericytomas (HPCs) are rare tumors that closely mimic meningiomas. However, in contrast to meningiomas, HPCs have a relatively high incidence of local recurrence and distant metastases, manifesting the need for sensitive noninvasive methods of detection that efficiently image the entire body. We present a rare case of a right optic nerve sheath HPC in which we identified a previously unknown distant metastasis in the thoracic spine on an 111In-pentetreotide scan. We detail the radiologic characteristics seen with somatostatin receptor imaging, FDG PET, and MRI and discuss how to exploit these findings to detect recurrence and metastatic disease in HPC. PMID- 24212444 TI - Successful treatment of metastasized pancreatic vasoactive intestinal polypeptide secreting tumor unresponsive to high-dose octreotide by peptide receptor radionuclide therapy using 90Y DOTATATE. AB - We report a successful treatment of a patient with heavily metastasized pancreatic vasoactive intestinal polypeptide-secreting tumor, which was unresponsive to high doses of octreotide analog using peptide receptor radionuclide therapy applying a radiolabeled somatostatin analog. After the peptide receptor radionuclide therapy, there was a decrease in vasoactive intestinal polypeptide levels, a significant reduction in somatostatin receptor expression and in molecular tumor volume on 68Ga DOTANOC PET/CT scan, and a complete long-term resolution of symptoms of the patient. PMID- 24212445 TI - 18F-FDG PET/CT imaging in primary cardiac angiosarcoma: diagnosis and follow-up. AB - A 40-year-old woman presented with recurrent chest tightness and shortness of breath for 10 days. The echocardiogram and MRI revealed a mass in the right atrium. FDG PET/CT was performed for further evaluation. The images demonstrated abnormally increased activity in the right atrial mass. The result of pathological examination after the surgical removal of the mass was consistent with angiosarcoma. Despite of receiving aggressive therapy including radiation, the patient had recurrent and metastatic malignancy 8 months later. PMID- 24212446 TI - Rest myocardial perfusion scintigraphy showing the invasion of the hydatid cyst in the myocardium. AB - A cardiac hydatid cyst is a rare complication of the Echinococcus infection, and it is seen in just 0.5% to 2% of all cases. Because it can cause sudden death, removing the cyst is recommended. It is important to determinate the relationship between the cyst and the intra/extracardiac structures before the operation because it is of vital importance during the operation. In our case, we showed that rest myocardial perfusion scintigraphy provided an additional contribution to anatomic imaging in that it showed the invasion of the cyst in the myocardium, which was effectively directing the course of the operation. PMID- 24212447 TI - Subcutaneous injection of 99mTc-pertechnetate for neonatal thyroid scintigraphy. AB - A 9-day-old female infant with congenital hypothyroidism presented for thyroid scintigraphy. Multiple attempts including the "intravenous team" failed to establish peripheral access for administration of 99mTc-pertechnetate. We administered 99mTc-pertechnetate subcutaneously into the upper arm. Rapid absorption (85% of the dose in 20 minutes) was documented on dynamic images with physiological uptake, allowing diagnostic thyroid scintigraphy at 35 minutes that revealed ectopic sublingual thyroid. Subcutaneous injection allowed us to avoid traumatic and risky central vascular access procedure. When peripheral intravenous access cannot be obtained, 99mTc-pertechnetate can be administered subcutaneously for diagnostic thyroid scintigraphy, which is particularly useful in neonates. PMID- 24212448 TI - Hallucal sesamoiditis manifested on bone scan. AB - The first metatarsal articulation bears one third of the weight of the forefoot. The hallucal sesamoids are embedded in the flexor hallucis brevis and connected by the intersesamoid ligament and plantar plate. The sesamoid apparatus acts as a pulley to help pull the big toe down against the ground during walking. Repetitive pressure, force, or tension can cause sesamoiditis. If the impact is great enough, the bones can break. Here we present a woman with big toe pain during walking. Our case highlights the role of 99mTc-MDP bone scan in reaching the diagnosis of hallucal sesamoiditis. PMID- 24212449 TI - Imaging of a case of metaplastic thymoma on 18F-FDG PET/CT. AB - Metaplastic thymoma is a rare primary thymic epithelial tumor. This report presents the 18F-FDG PET/CT appearance of a metaplastic thymoma developed in a 61 year-old female patient. The FDG uptake of the mediastinal mass showed a high maximum SUV, thus suggesting the possibility of thymic cancer. Surgical resection was performed for both a definitive diagnosis and treatment of the mediastinal tumor. A histological examination of the resected specimen revealed metaplastic thymoma. Although rare, thymoma should be carefully considered in the differential diagnosis in cases of mediastinal masses presenting with highly positive findings on 18F-FDG PET/CT to avoid any inappropriate patient management. PMID- 24212450 TI - Adsorption of 99mTc-sestamibi onto plastic syringes: evaluation of factors affecting the degree of adsorption and their impact on clinical studies. AB - The purpose of this study was to document the extent of adhesion of (99m)Tc sestamibi to syringes in patient procedures, determine factors that influence the degree of adhesion, and evaluate alternatives to our current practice that would either result in a more reproducible degree of adhesion or, ideally, eliminate adhesion. METHODS: The extent of adhesion was documented in 216 patient procedures and evaluated in detail in an additional 73 patient procedures. We evaluated the nature of the adhesion and its possible causes, including the location of adhesion in injection sets, the effect of syringe type, and the effect of prerinsing of syringes with various solutions of nonradiolabeled sestamibi and (99m)Tc-sestamibi. The extent of adhesion was reevaluated in 50 procedures performed using the syringe type that demonstrated the lowest adhesion rate. RESULTS: The degree of adhesion of (99m)Tc-sestamibi to the injection set was found to be 20.1% +/- 8.0%, with a range (10th-90th percentiles) of 9%-31%. The primary cause of adhesion appeared to be the lubricant used inside the syringe barrel. Evaluation of 6 different syringe types identified a brand with a lower adhesion rate. Reevaluation in patient procedures using this brand showed a 5.2% +/- 2.5% degree of adhesion, with a range (10th-90th percentiles) of 2.5% 7.7%. CONCLUSION: Selection of the appropriate type of syringe can significantly reduce the magnitude and variability of residual (99m)Tc-sestamibi activity. With more reproducible residual activities, we have been able to achieve an approximately 20% reduction in the dispensed dose of (99m)Tc-sestamibi used in clinical procedures and a more consistent injected dose with less interpatient variation. The frequent changes in syringe design by manufacturers require that a quality control program for monitoring of residual activity be incorporated into clinical practice. This program has allowed us to maintain image quality and achieve more consistent injected patient doses in clinical procedures that use (99m)Tc-sestamibi. PMID- 24212452 TI - Editorial. PMID- 24212451 TI - Changes in body anthropometry and composition in obese adolescents in a lifestyle intervention program. AB - PURPOSE: Impact of lifestyle modification on obesity control during adolescence, a period of significant physical growth and development, is less quantitatively evaluated. Therefore, we investigated the impact of changes in reported energy intake and physical activity on anthropometrics and body composition in adolescents. METHODS: Participants were obese adolescents aged 11-18 years. All of them have a body mass index (BMI) >= 95th percentile specific for age and gender according to the 2000 CDC Growth Charts. The intervention consists of supervised physical activity, structured nutrition education and dietary modification, and behavioral support in 6 months. Hundred and forty-five obese adolescents completed the study. RESULTS: Compared to baseline, significant reductions in body weight (-1.4 kg, p < 0.001) and BMI (-0.1 kg/m(2), p < 0.001) were observed at 6 months. When compared to expected growth trajectories on the 2000 CDC Growth Charts, body weight and BMI were reduced by 3.6 kg and 1.5 kg/m(2), respectively, in boys and 5.6 kg and 1.9 kg/m(2) in girls. Age was inversely associated with changes in weight (beta = -1.48 kg, p < 0.01) and BMI (beta = -0.32 kg/m(2), p = 0.03). There was a dose-response relationship between reduction in energy intake and weight loss. A decrease of 100 kcal/day was significantly associated with reductions in body weight 0.30 kg, BMI 0.09 kg/m(2), and BMI Z score 0.01 (all p < 0.01). Physical activity was not significantly associated with changes in anthropometrics or body composition. CONCLUSIONS: Reduction in energy intake was a significant predictor of obesity reduction in these adolescents. A quantitative evaluation of adolescent weight loss programs should account for natural growth and development. PMID- 24212453 TI - Genetic engineering of microorganisms for biotechnology. PMID- 24212454 TI - Ecology of food microorganisms. AB - The behavior of microorganisms in foods is governed by the constraints applied to the microflora by a variety of environmental and ecological factors. These include water activity, pH, Eh, chemical composition, the presence of natural or added antimicrobial compounds, and storage temperature, as well as processing factors such as the application of heat and physical manipulation. Control of these factors will govern whether the food spoils or not, whether any microbial health hazard arises, and whether desired microbial processes are successful or not. While much is known about the effects of individual environmental factors, the effects due to their interactions are less understood. The two main problems now facing the food microbiologist are optimization of environmental parameters and the selection of strains with specific properties. A better understanding of the mechanisms of action and interactions between the various environmental factors, coupled with the application of modern techniques to produce strains with particular properties, will lead to optimum use of food supplies and improvements in quality. There is also potential for the development of new and novel foods. PMID- 24212455 TI - Ecology of yeasts with actual and potential value in biotechnology. PMID- 24212456 TI - The ecology of antibiotic production. AB - Over the last 40 years, there has been a steady supply of novel, useful antibiotics produced by microbes isolated from soil and other natural environments. The increased efficiency of screening procedures in the last decade has played a major part in maintaining this supply. However, the selection and sampling of natural environments are still essentially random processes. The main reasons for this are an almost total lack of knowledge of the significance of antibiotics in nature, deficiencies in the taxonomy of antibiotic-producing microbes and its application, and lack of information about the distribution and ecology of known or potential antibiotic producers. The origins of these problems are discussed and some possible solutions are suggested. PMID- 24212457 TI - Biotechnology and ecological studies on the oral cavity. PMID- 24212458 TI - Marine microorganisms as a source of bioactive agents. AB - Several ecological factors of the marine environment were used in developing a strategy for discovering useful bioactive agents from marine microorganisms. By consideration of sea water requirements, production and degradation of marine polymers, and plasmid content, several novel anti-malarial antibiotics, anti tumor polysaccharides, glucan-degrading enzymes, and aminoglycoside antibiotics were found. PMID- 24212459 TI - Potential commercial applications in aquatic microbiology. PMID- 24212460 TI - Microbial-invertebrate interactions and potential for biotechnology. AB - CONCLUSION: As the interactions between marine invertebrates and their bacterial commensals and symbionts are better understood, the application of biotechnology will enhance both environmental and economic benefit. In the immediate future, marine bacteria, either selected or genetically engineered, will play a significant role in enhancing the development of selected invertebrates in aquaculture and in the field. Luck may also favor discovery of mechanisms to suppress the development of biofouling species, perhaps by making it possible to coat submerged surfaces with bacterial films designed to repell larvae and/or interfere with larval morphogenesis. In any case, the future is appealing. PMID- 24212461 TI - The biotechnological future for newly described, extremely thermophilic bacteria. AB - Recent explorations of aquatic volcanic environments have led to the isolation of novel microorganisms with optimal growth temperatures of 80 degrees C or higher. Expectations of equally novel, highly thermostable biocatalysts and specialty chemicals from such organisms remain high but must be tempered with the laboratory realities of manipulating unusual bacteria whose growth characteristics are as yet poorly defined. Advancing the biotechnological future of "super-thermophiles" will require new cultivation methods, including the use of highly thermostable gels and pressurized bioreactors. PMID- 24212462 TI - Screening for a "new" enzyme in nature: Haloperoxidase production by Death Valley dematiaceous hyphomycetes. AB - Haloperoxidases are enzymes that have the ability to halogenate a broad range of substrates [10]. To find a biologically produced haloperoxidase that could function at a pH greater than 3.0 and at a temperature greater than 19 degrees C, dematiaceous hyphomycetes were isolated from the Death Valley desert and screened for their ability to produce such an enzyme. A qualitative assay using bromophenol red was employed in situ over a 12-day fermentation period. Several dematiaceous hyphomycetes, such asDreschlera haloides andUlocladium chartarum, produced haloperoxidases that were active in broth culture at 19, 25, and 34 degrees C at pH 7.0 and 8.0. PMID- 24212463 TI - Genetic control of environmental pollutants: A conference review. PMID- 24212464 TI - Genetic aspects of toxic chemical degradation. AB - All naturally occurring molecules are continuously being recycled in nature, constantly being synthesized, and constantly being degraded. Synthetic molecules on the other hand, often are unable to enter nature's recycling scheme because organisms that have an ability to degrade these xenobiotic compounds simply do not exist. Moreover, many synthetic chemicals are not only recalcitrant to biodegradation, but also are toxic and therefore can cause significant pollution problems even at very low concentrations. The chemical industry will continue to produce an evergrowing number of molecules, even though severe environmental problems have resulted from synthetic molecules already produced. We must find a means of bringing synthetic molecules back into nature's recycling systems if we are to preserve the environment. Biotechnology, through the genetic manipulation of microorganisms, provides a means of accomplishing this goal. PMID- 24212465 TI - Anaerobic degradation of halogenated aromatic compounds. AB - Recent microbiological findings show how compounds, regarded hitherto as unusual substrates for anaerobic bacteria, are degraded under anaerobic conditions. The complete conversion of halobenzoic acids and halophenolic compounds to methane by lake sediment and sewage sludge microorganisms has been demonstrated. Since haloaromatic compounds are widely used and may be found in such effluents as those from the forest industry, these studies could stimulate a broader interest in anaerobic treatment of industrial waste waters which contain unusual organic compounds. PMID- 24212466 TI - Biotechnology of petroleum pollutant biodegradation. AB - Procedures designed to meet the physiological needs of petroleum hydrocarbon (PHC) degrading microorganisms are useful in mitigating environmental damage caused by marine and terrestrial PHC spills. By similar approaches, soil can be utilized as a cost-effective biological incinerator for hazardous PHC wastes. Physiological ecology needs to complement genetic engineering efforts for an effective attack on environmental pollution problems. PMID- 24212468 TI - In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent. AB - In this study, a peptide-based dual-targeting magnetic resonance imaging (MRI) contrast agent (S8) was designed and synthesized. Arg-Gly-Asp (RGD) and Asn-Gly Arg (NGR) were combined in the targeting vector so as to allow binding, on the surface of tumor cells, to integrin alphavbeta3 and aminopeptidase N (CD13), respectively. The longitudinal relaxivity (r1) value of S8 was 8.297 mM-1sec-1 at a magnetic field of 11.7 T, which is approximately double the r1 value (4.25 mM 1sec-1) of Magnevist, a commercially available contrast agent. MDA-MB-231 human breast cancer cells (which overexpress alphavbeta3) and human prostate cancer cells PC-3 (which overexpress CD13) were used to investigate the tumor-targeting behavior of S8. The results from the present study indicate that the designed contrast agent, S8, targets both MDA-MB-231 and PC-3 cells. PMID- 24212467 TI - C(m)CGG methylation-independent parent-of-origin effects on genome-wide transcript levels in isogenic reciprocal F1 triploid plants. AB - Triploid F1 hybrids generated via reciprocal interploidy crosses between genetically distinct parental plants can display parent-of-origin effects on gene expression or phenotypes. Reciprocal triploid F1 isogenic plants generated from interploidy crosses in the same genetic background allow investigation on parent of-origin-specific (parental) genome-dosage effects without confounding effects of hybridity involving heterozygous mutations. Whole-genome transcriptome profiling was conducted on reciprocal F1 isogenic triploid (3x) seedlings of A. thaliana. The genetically identical reciprocal 3x genotypes had either an excess of maternally inherited 3x(m) or paternally inherited 3x(p) genomes. We identify a major parent-of-origin-dependent genome-dosage effect on transcript levels, whereby 602 genes exhibit differential expression between the reciprocal F1 triploids. In addition, using methylation-sensitive DNA tiling arrays, constitutive and polymorphic CG DNA methylation patterns at CCGG sites were analysed, which revealed that paternal-excess F1 triploid seedling C(m)CGG sites are overall hypermethylated. However, no correlation exists between C(m)CGG methylation polymorphisms and transcriptome dysregulation between the isogenic reciprocal F1 triploids. Overall, our study indicates that parental genome-dosage effects on the transcriptome levels occur in paternal-excess triploids, which are independent of C(m)CGG methylation polymorphisms. Such findings have implications for understanding parental effects and genome-dosage effects on gene expression and phenotypes in polyploid plants. PMID- 24212469 TI - Dynamic investigation of interface atom migration during heterostructure nanojoining. AB - Interface atom migration and compositional evolution during the heterostructure nanojoining process under external electrical loadings has been investigated in situ inside a transmission electron microscope with atomic resolution. The results indicate that the migration of oxygen atoms on the contact interface of metal nanorods is a thermal dominated process rather than an electromigration process. After removing the oxide layer at the nanometal contact interface, the metal atoms migrate under external electrical field. The formation region of nanoalloys can be modulated by controlling the electromigration direction of nanometal atoms, leading to an electromigration-dominated cutting process which offers an extra degree of freedom to design a sacrifice layer and interconnects in solid-state bonding. These findings offer an insight of potential failure mechanisms as well as fabrication methodology for interconnects in nanodevices. PMID- 24212470 TI - Standard tobacco packaging still being considered but is not a "silver bullet," says health department. PMID- 24212471 TI - Improvement of alkali stability and thermostability of Paenibacillus campinasensis Family-11 xylanase by directed evolution and site-directed mutagenesis. AB - The extreme process condition of high temperature and high alkali limits the applications of most of natural xylanases in pulp and paper industry. Recently, various methods of protein engineering have been used to improve the thermal and alkalic tolerance of xylanases. In this work, directed evolution and site directed mutagenesis were performed to obtain a mutant xylanase improved both on alkali stability and thermostability from the native Paenibacillus campinasensis Family-11 xylanase (XynG1-1). Mutant XynG1-1B43 (V90R/P172H) with two units increased in the optimum pH (pH 7.0-pH 9.0) and significant improvement on alkali stability was selected from the second round of epPCR library. And the further thermoduric mutant XynG1-1B43cc16 (V90R/P172H/T84C-T182C/D16Y) with 10 degrees C increased in the optimum temperature (60-70 degrees C) was then obtained by introducing a disulfide bridge (T84C-T182C) and a single amino acid substitution (D16Y) to XynG1-1B43 using site-directed mutagenesis. XynG1-1B43cc16 also showed higher thermostability and catalytic efficiency (k cat /K m ) than that of wild type (XynG1-1) and XynG1-1B43. The attractive improved properties make XynG1 1B43cc16 more suitable for bioleaching of cotton stalk pulp under the extreme process condition of high temperature (70 degrees C) and high alkali (pH 9.0). PMID- 24212472 TI - DyP-type peroxidases: a promising and versatile class of enzymes. AB - DyP peroxidases comprise a novel superfamily of heme-containing peroxidases, which is unrelated to the superfamilies of plant and animal peroxidases. These enzymes have so far been identified in the genomes of fungi, bacteria, as well as archaea, although their physiological function is still unclear. DyPs are bifunctional enzymes displaying not only oxidative activity but also hydrolytic activity. Moreover, these enzymes are able to oxidize a variety of organic compounds of which some are poorly converted by established peroxidases, including dyes, beta-carotene, and aromatic sulfides. Interestingly, accumulating evidence shows that microbial DyP peroxidases play a key role in the degradation of lignin. Owing to their unique properties, these enzymes are potentially interesting for a variety of biocatalytic applications. In this review, we deal with the biochemical and structural features of DyP-type peroxidases as well as their promising biotechnological potential. PMID- 24212473 TI - Genome-guided discovery of diverse natural products from Burkholderia sp. AB - Burkholderia species have emerged as a new source of diverse natural products. This mini-review covers all of the natural products discovered in recent years from Burkholderia sp. by genome-guided approaches--these refer to the use of bacterial genome sequence as an entry point for in silico structural prediction, wet lab experimental design, and execution. While reliable structural prediction based on cryptic biosynthetic gene cluster sequence was not always possible due to noncanonical domains and/or module organization of a deduced biosynthetic pathway, a molecular genetic method was often employed to detect or alter the expression level of the gene cluster to achieve an observable phenotype, which facilitated downstream natural product purification and identification. Those examples of natural product discovery from Burkholderia sp. provide practical guidance for future exploration of Gram-negative bacteria as a new source of natural products. PMID- 24212474 TI - Molecular basis of wing coloration in a Batesian mimic butterfly, Papilio polytes. AB - Batesian mimicry protects animals from predators through resemblance with distasteful models in shape, color pattern, or behavior. To elucidate the wing coloration mechanisms involved in the mimicry, we investigated chemical composition and gene expression of the pale yellow and red pigments of a swallowtail butterfly, Papilio polytes, whose females mimic the unpalatable butterfly Pachliopta aristolochiae. Using LC/MS, we showed that the pale yellow wing regions in non-mimetic females consist of kynurenine and N-beta alanyldopamine (NBAD). Moreover, qRT-PCR showed that kynurenine/NBAD biosynthetic genes were upregulated in these regions in non-mimetic females. However, these pigments were absent in mimetic females. RNA-sequencing showed that kynurenine/NBAD synthesis and Toll signaling genes were upregulated in the red spots specific to mimetic female wings. These results demonstrated that drastic changes in gene networks in the red and pale yellow regions can switch wing color patterns between non-mimetic and mimetic females of P. polytes. PMID- 24212475 TI - The mechanism of caesium intercalation of graphene. AB - Properties of many layered materials, including copper- and iron-based superconductors, topological insulators, graphite and epitaxial graphene, can be manipulated by the inclusion of different atomic and molecular species between the layers via a process known as intercalation. For example, intercalation in graphite can lead to superconductivity and is crucial in the working cycle of modern batteries and supercapacitors. Intercalation involves complex diffusion processes along and across the layers; however, the microscopic mechanisms and dynamics of these processes are not well understood. Here we report on a novel mechanism for intercalation and entrapment of alkali atoms under epitaxial graphene. We find that the intercalation is adjusted by the van der Waals interaction, with the dynamics governed by defects anchored to graphene wrinkles. Our findings are relevant for the future design and application of graphene-based nano-structures. Similar mechanisms can also have a role for intercalation of layered materials. PMID- 24212476 TI - Perceptions and perceived impact of graphic cigarette health warning labels on smoking behavior among U.S. young adults. AB - INTRODUCTION: In 2011, the Food and Drug Administration published a final rule requiring cigarette packages and advertisements to include graphic health warning labels (HWLs) with new warning statements. Implementation of this rule has been stalled by legal challenge. This study assessed correlates of smoking-related intentions related to graphic HWLs among current cigarette smokers and nonsmokers in a national sample of U.S. young adults aged 18-34. METHODS: Data were collected from 4,236 participants aged 18-34 using an online panel in January 2012 for the Legacy Young Adult Cohort Study. Analyses were weighted to provide nationally representative estimates. Our main outcome was assessed with a single item: "Do you think that new warning labels with graphic pictures would make you think about not smoking?" RESULTS: Twenty-two percent of the young adults were current cigarette smokers. Fifty-three percent endorsed that new graphic HWLs would make them think about not smoking (40% among current smokers compared with 56% among nonsmokers). Among nonsmokers, those aged 18-24, females, Hispanics, and those who were aware of graphic cigarette HWLs were more likely to report intention to not smoke related to graphic HWLs. Among current smokers, intending to quit within the next 6 months was correlated with intention resulting from graphic HWLs. Hispanic ethnicity and intention to quit within 30 days were strong correlates of intention in light, nondaily, and self-identified social/occasional smokers. CONCLUSIONS: This study supports previous findings that graphic HWLs play an important role in preventing smoking, in addition to encouraging cessation in young adults. PMID- 24212477 TI - Prematurational culture with 3-isobutyl-1-methylxanthine synchronizes meiotic progression of the germinal vesicle stage and improves nuclear maturation and embryonic development in in vitro-grown bovine oocytes. AB - The objective of this study was to clarify the effects of prematurational culture (pre-IVM) supplemented with 3-isobutyl-1-methylxanthine (IBMX) on nuclear and cytoplasmic maturation of in vitro-grown bovine oocytes. In experiment 1, oocytes (95 MUm in diameter) derived from early antral follicles (0.5-1 mm in diameter) were cultured for 12 days for in vitro growth (IVG). IVG oocytes with a normal appearance were subjected to examinations of diameter and chromatin structure in the germinal vesicle (GV) before IVM. In addition, percentages of metaphase II (M II) were examined after IVM. Regardless of pre-IVM, the mean diameters of IVG oocytes were about 115 MUm. The proportions of GV3 (50.0%) and M II stages (80.1%) of IVG oocytes with pre-IVM were higher than those without pre-IVM (28.0 and 49.4%, respectively). In experiment 2, the fertilizability and developmental competence of IVG oocytes were examined. Regardless of pre-IVM, the normal fertilization rates of IVG oocytes were similar (around 70%) but were lower than that of in vivo-grown oocytes (88.0%). Cleavage and blastocyst rates of IVG oocytes with pre-IVM (63.0 and 26.1%, respectively) were higher than those without pre-IVM (45.8 and 12.7%, respectively). The blastocyst rate based on cleaved IVG oocytes with pre-IVM (41.7%) was similar to that of in vivo-grown oocytes (48.7%), although the cleavage rate of IVG oocytes with pre-IVM was lower than that of in vivo-grown oocytes. In conclusion, pre-IVM with IBMX improved the maturational and developmental competences of IVG oocytes, probably due to promotion of their chromatin transition and synchronization of meiotic progression. PMID- 24212478 TI - A comparison of spinal anesthesia characteristics following intrathecal bupivacaine or levobupivacaine in lumbar disc surgery. AB - PURPOSE: While bupivacaine is the most frequently used local anesthetic for spinal anesthesia, use of levobupivacaine in clinical practice has advanced recently. The aim of our study was to compare the clinical and anesthetic effects of isobaric bupivacaine and isobaric levobupivacaine when administered intrathecally in patients undergoing lumbar disc surgery. METHODS: ASA I-III, 60 patients were enrolled in this study. Only patients with unilateral single-level (L4-5) lumbar disc hernia were selected and operated in each group and all were operated by the same surgeon. Patients were randomized into two groups, as group B (n = 30): 15 mg 0.5% isobaric bupivacaine, or group L (n = 30): 15 mg 0.5% isobaric levobupivacaine received intrathecally. The level of sensory block dermatome, degree of motor block, intraoperative sensory and motor block characteristics, and postoperative recovery times of spinal anesthesia were evaluated. The satisfaction scores of the surgeon and patients, intraoperative hemodynamic changes, intraoperative and postoperative complications were recorded. RESULTS: The maximum level of sensory blockade was significantly higher in the levobupivacaine group (group L 7 +/- 1.63, group B 8.6 +/- 1.76 thoracic dermatome, p < 0.05). There was no significant difference in the onset time of sensory (group L 6 +/- 3 min, group B 9 +/- 4 min) and motor (in group L 7 +/- 3 min, in group B 10 +/- 4 min) blockade (p > 0.05). There was no significant difference between the groups regarding duration of operation (group L 49 +/- 7.3 min, group B 52 +/- 8.1, p > 0.05). Recovery times of sensory (175 +/- 57 min) and motor (216 +/- 59 min) blockade were significantly shorter in the levobupivacaine group (p < 0.05). Mobilization was also earlier in the levobupivacaine group (339 +/- 90 min, p < 0.05). Patients' satisfaction and intraoperative, postoperative complications were similar between the two groups. CONCLUSIONS: Our results showed that block recovery time was shorter in the levobupivacaine group, this may be a disadvantage for longer operative procedures. But with proper patient selection this can be eliminated. Recovery time was shorter in levobupivacaine group. Therefore, postoperative neurological examination can be done earlier. In addition, early mobilization can be an advantage for postoperative recovery. PMID- 24212479 TI - Long-term result of vocal cord paralysis after anterior cervical disectomy. AB - PURPOSE: Anterior cervical disectomy and fusion (ACDF) is a highly effective and safe method for spinal cord and cervical root decompression. However, vocal cord paralysis (VCP) remains an important cause of postoperative morbidity. The true incidence and recovery course of postoperative VCP is still uncertain. This study is a report on VCP after ACDF to evaluate the incidence, recovery course, and possible risk factors. METHODS: From 2004 to 2008, 1,895 consecutive patients underwent ACDF in our hospital and were followed up for at least 3 years. All surgeons were well trained and used a right-sided exposure. Prolonged VCP, where patients suffered from postoperative VCP lasting more than 3 months, was recorded and analyzed. RESULTS: In this retrospective study, 9 of the 1,895 patients (0.47%) documented prolonged VCP lasting over 3 months. Six of the nine patients had total recovery within 9 months. Only three patients (0.16%) still had symptoms even after 3 years postoperatively. All symptoms of VCP, except hoarseness, could be improved. After matching with 36 non-VCP patients, no differences with regard to longer operative or anesthesia time, shorter neck, obesity, and prevertebral edema. All cases of prolonged course of postoperative VCP occurred in patients who underwent exposure at the C67 level. CONCLUSION: In our study, only 0.47% documented prolonged postoperative VCP, while most patients recovered within 9 months. However, if symptoms last longer, there could be almost permanent VCP (0.16%). In our study, choking and dysphagia subsided mostly within 6 months, but hoarseness remained. The exposure of the C67 level obviously was a risk factor for postoperative VCP. PMID- 24212480 TI - Incidental dural tear in spine surgery: analysis of a nationwide database. AB - PURPOSE: The purpose of this study was to report the incidence of dural tear (DT) in spine surgery, risk factors, and patient outcomes on a national level. METHODS: Clinical data were obtained from the Nationwide Inpatient Sample for 2009. Patients who underwent spine surgery were identified and, among them, patients who had DT were identified, according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes. Patient and hospital demographic data were retrieved. The incidence of DT and in hospital patient outcomes were analyzed. Multivariate logistic regression analysis was performed to identify the risk factors for DT. RESULTS: The incidence of DT was 2.7 % (17,932/665,818). Multivariate analysis revealed that older age, female gender, increased Elixhauser comorbidity score, and high hospital caseload were the significant risk factors for DT. Comparison between patients with and without DT showed that those with DT had significantly higher overall in-hospital complications (18.8 vs. 10.2 %), higher in-hospital mortality rate (0.4 vs. 0.3 %), longer hospital stays (5.1 vs. 3.7 days), lower proportion discharged home routinely (61.0 vs. 76.8 %), and increased total hospital charges ($85,138 vs. $71,808), respectively. CONCLUSIONS: The reported incidence of DT in spine surgery was 2.7 % in the US. Risk factors included older age, female gender, increased comorbidities, and high hospital caseload. DT increased the rate of in-hospital complications and mortality and health care burdens. PMID- 24212482 TI - ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia. PMID- 24212483 TI - CSF3R T618I co-occurs with mutations of splicing and epigenetic genes and with a new PIM3 truncated fusion gene in chronic neutrophilic leukemia. PMID- 24212484 TI - Identification of associating carbohydrate sequences with labelled oligosaccharides : Localization of alginate-gelling subunits in cells walls of a brown alga. AB - The gelling subunit of alginate, the major cell-wall polysaccharide of brown algae, was used as a molecular marker for identification of this cell-wall carbohydrate subunit at the cellular level. Short polyguluronate chains were conjugated to fluorescein and used as a probe to identify the gelling regions of alginate in tissue sections from a brown alga. The specificity of the probe for gelling subunits was demonstrated by lack of cell-wall labelling in the absence of calcium, correlation between divalent-cation binding affinities of polyguluronate with labelling intensity, and lack of labelling by fluorescein conjugated nongelling subunits. The probe labelling-pattern also differed from sulfated fucan distribution. Extracellular matrix and cell walls were labelled on sections of vegetative blade, stipe and reproductive frond of Fucus gardneri Silva. Probe labelling was rapid, being virtually complete within 5 min. Probe labelling in seawater differed markedly from labelling at lower ionic strength and is interpreted as reflecting alginategelling properties in natural conditions. High-and low-affinity binding sites are discussed in terms of gelling subunit length and steric availability. Fluorescein-conjugated polygalacturonate, which also forms calcium dimers, labelled extracellular alginate by formation of mixed polygalacturonate-polyguluronate dimers. Binding by the alginate hybridization probe differs from nucleic-acid hybridization in divalent-cation bridging and the lack of both a conformational transition and polymer polarity. PMID- 24212485 TI - Pectate distribution and esterification in Dubautia leaves and soybean nodules, studied with a fluorescent hybridization probe. AB - Carbohydrate-hybridization probes (Vreeland and Laetsch, 1989, Planta (177, 423 434) were used to localize the homogalacturonan (pectate) component of pectins in the cell walls of leaves and soybean root nodules. Leaves of two species of the dicotyledon Dubautia were compared; these species contain much pectin but differ in their tissue water relations with respect to their cell-wall properties. Maturation of the primary cell walls in nodules was studied in the Bradyrhizobium japonicum-Glycine max symbiosis. Probe labelling was based on the divalent-cation mediated association between pectate in tissue sections and fluorescein conjugated pectate fragments. Pectate was also labelled by mixed-dimer formation with fluorescent polyguluronate derived from alginate. The specificity of the probe for unesterified polygalacturonate was indicated by increased cell-wall labelling after chemical or enzymatic deesterification of tissue sections, in contrast to elimination of labelling by chemical esterification. Postfixation of tissue sections improved retention of soluble pectate. Pectate differences were found in the leaves among cell types, in degree of esterification, and between plant species. The cell walls of soybean nodules were strongly labelled by the pectate probe in nodules one week and three weeks after infection. Pectate was more highly esterified in the central infected zone than in the surrouding cortex. Within the infected zone, walls of uninfected cells and infected cells were similarly labelled by the pectate probe. The results indicate that the pectate molecular probe provides detailed information on pectate distribution at the cellular level for investigations of cell-wall structure, development and physiology. PMID- 24212486 TI - Chitinase in roots of mycorrhizal Allium porrum: regulation and localization. AB - Chitinase (EC 3.2.1.14) activity was measured in roots of Allium prorrum L. (leek) during development of a vesicular-arbuscular mycorrhizal symbiosis with Glomus versiforme (Karst.) Berch. During the early stages of infection, between 10 and 20 d after inoculation, the specific activity of chitinase was higher in mycorrhizal roots than in the uninfected controls. However, 60-90 d after inoculation, when the symbiosis was fully established, the mycorrhizal roots contained much less chitinase than control roots. Chitinase was purified from A. porrum roots. An antiserum against beanleaf chitinase was found to cross-react specifically with chitinase in the extracts from non-mycorrhizal and mycorrhizal A. porrum roots. This antiserum was used for the immunocytochemical localization of the enzyme with fluorescent and gold-labelled probes. Chitinase was localized in the vacuoles and in the extracellular spaces of non-mycorrhizal and mycorrhizal roots. There was no immunolabelling on the fungal cell walls in the intercellular or the intracellular phases. It is concluded that the chitin in the fungal walls is inaccessible to plant chitinase. This casts doubts on the possible involvement of this hydrolase in the development of the mycorrhizal fungus. However, fungal penetration does appear to cause a typical defense response in the first stages that is later depressed. PMID- 24212487 TI - Period and phase control by temperature in the circadian rhythm of carbon dioxide fixation in illuminated leaves of Bryophyllum fedtschenkoi. AB - The rhythm of CO2 assimilation exhibited by leaves of Bryophyllum fedtschenkoi maintained in light and normal air occurs only at constant ambient temperatures between 10 degrees C and 30 degrees C. Over this range the period increases linearly with increasing temperature from the extremely low value of 15.7 h to 23.3 h, but shows a considerable degree of temperature compensation. Outside the range 10 degrees C-30 degrees C the rhythm is inhibited but re-starts on changing the temperature to 15 degrees C. Prolonged exposure of leaves to high (40 degrees C) and low (2 degrees C) temperature inhibits the rhythm by driving the basic oscillator to fixed phase points in the cycle which differ by 180 degrees , and which have been characterised in terms of the malate status of the leaf cells. At both temperatures loss of the circadian rhythm of CO2 assimilation is due to the inhibition of phosphoenolpyruvate carboxylase (PEPCase) activity, but the inhibition is apparently achieved in different ways at 40 degrees C and 2 degrees C. High temperature appears to inhibit directly PEPCase activity, but not the activity of the enzymes responsible for the breakdown of malate, with the result that the leaf acquires a low malate status. In contrast, low temperature does not directly inhibit PEPCase activity, but does inhibit enzymes responsible for malate breakdown, so that the malate level in the leaf increases to a high value and PEPCase is eventually allosterically inhibited. The different malate status of leaves held at these two temperatures accounts for the phases of the rhythms being reversed on returning the leaves to 15 degrees C. After exposure to high temperature, CO2 fixation by PEPCase activity can begin immediately, whereas after exposure to low temperature, the large amount of malate accumulated in the leaves has to be decarboxylated before CO2 fixation can begin. PMID- 24212488 TI - Latent nitrate reductase activity is associated with the plasma membrane of corn roots. AB - Latent nitrate reductase activity (NRA) was detected in corn (Zea mays L., Golden Jubilee) root microsome fractions. Microsome-associated NRA was stimulated up to 20-fold by Triton X-100 (octylphenoxy polyethoxyethanol) whereas soluble NRA was only increased up to 1.2-fold. Microsome-associated NRA represented up to 19% of the total root NRA. Analysis of microsomal fractions by aqueous two-phase partitioning showed that the membrane-associated NRA was localized in the second upper phase (U2). Analysis with marker enzymes indicated that the U2 fraction was plasma membrane (PM). The PM-associated NRA was not removed by washing vesicles with up to 1.0 M NACl but was solubilized from the PM with 0.05% Triton X-100. In contrast, vanadate-sensitive ATPase activity was not solubilized from the PM by treatment with 0.1% Triton X-100. The results show that a protein capable of reducing nitrate is embedded in the hydrophobic region of the PM of corn roots. PMID- 24212489 TI - Role of acid efflux during growth promotion of primary leaves of Phaseolus vulgaris L. by hormones and light. AB - The white-light-(WL) induced enlargement of dicotyledonous leaf cells is known to occur via an acid-growth mechanism; i.e., WL causes leaf cells to excrete protons which lead to an increase in wall extensibility and thus cell enlargement. Gibberellic acid (GA3) and N(6)-benzyladenine (BA) also induce leaf cell enlargement. To see if they also act via acid-induced cell wall loosening, a comparison has been made of WL-, GA3-and BA-induced growth of strips, taken from primary leaves of bean (Phaseolus vulgaris L.) plants raised in continuous red light for 10 d. White light, GA3 and BA all increased wall extensibility as measured by the Instron technique, and this change preceded the increase in growth rate. However, whereas WL induced significant proton excretion, neither GA3 nor BA caused any acidification of the apoplast. Furthermore, neutral buffers, which effectively inhibited the growth induced by WL, were without effect on growth promoted by either GA3 or BA. These results indicate that while WL, GA3 and BA all initiate growth in bean leaves by altering cell-wall properties, GA3 and BA do so through some wall loosening mechanism other than wall acidification. Neither gibberellin nor cytokinin is likely to play a major role in light-induced cell enlargement of dicotyledonous leaves. PMID- 24212490 TI - Differential fractionation of oxygen isotopes by cyanide-resistant and cyanide sensitive respiration in plants. AB - Stable-isotope discrimination factors (D) for the uptake of oxygen during respiration by a variety of plant materials were determined by measuring (18)O enrichment in a closed system. Baker's yeast (Saccharomyces cerevisiae Meyer) and mitochondrial preparations from baker's yeast and from castor bean (Ricinus communis L.) endosperm, all of which are fully sensitive to cyanide, discriminated againt (18)O by about 16-180/00. Whole Medicago sativa L. seedlings, isolated intact Asparagus sprengeri Regel mesophyll cells, and spadix mitochondria of Eastern skunk cabbage (Symplocarpus foetidus L.) had higher Ds of about 20-220/00. These materials all had some capacity for the cyanide-resistant alternative respiration pathway and in the presence of cyanide discriminated by about 24-260/00. When treated with salicylhydroxamic acid or tetraethylthiuram disulfide, which inhibit the alternative pathway, discrimination was about 17 190/00. Where respiration was limited by oxygen diffusion (slices of thermogenic tissues from S. foetidus and Sauromatum gutfatum Schott), fractionation was much reduced and the difference between the two respiratory pathways was masked. Isotope discrimination by soybean lipoxygenase (EC 1.13.11.12) supplied with linoleic acid was much lower than by respiration. Where diffusion is not a problem, the D value obtained in the absence of inhibitor can be used to estimate the partitioning of electron transport between the two pathways at steady-state by linear interpolation between the Ds characteristic of cyanide-resistant and cyanide-sensitive respiration. PMID- 24212491 TI - Temporal control of phytochrome-dependent gene expression during radish seedling development. AB - The level of two nuclear-encoded transcripts (the small subunit of ribulose-1,5 bisphosphate carboxylase and the chlorophyll a/b-binding protein of photosystem II) and two chloroplastencoded mRNAs (the large subunit of ribulose-1,5 bisphosphate carboxylase and the chloroplast 32-kDa polypeptide) were analysed during the first 4 d of radish (Raphanus sativus L.) seedling development. A single 5-min red-light pulse increased the concentrations of all transcripts by various orders of magnitude, depending on the particular mRNA. For all transcripts the maximal effect of the red light was observed when the irradiation was applied 48 h following sowing. The red-light treatment did not lead to changes in the total RNA level or to alterations in the levels of nuclear and chloroplastic DNAs; the level of beta-actin mRNA was also unaffected by the light treatment. It is concluded that during the first days of development, cells of radish cotyledons undergo light-independent molecular changes, occurring at the transcriptional level, conferring on them a transient competence towards the photoreceptor phytochrome. PMID- 24212492 TI - Electrical properties of soybean plasma membrane measured in heterotrophic suspension callus. AB - Previous work on heterotrophic suspension-cultured cells has failed to detect the electrogenic processes normally associated with the plasma membranes of non animal cells. This study reports measurements on heterotrophic cells from soybean (Glycine max L.) suspension cultures, which are shown to be amenable to impalement with microelectrodes. The plasma membrane clearly exhibits fundamental characteristics which are common to many other plant cell types: (i) a resting membrane potential significantly more negative than-100mV (measured value:121+/ 4mV); (ii) obvious electrogenic activity, as evidenced by the marked depolarization of the membrane (87+/-6mV) by cyanide, and by the fact the membrane potential was frequently more negative than the equilibrium potential for K(+); (iii) a finite permeability to K(+) ions; (iv) electrophoretic transport of glucose. The development of a recording medium consisting primarily of 1:5 diluted growth medium was critical for successful impalement of these cells. It is proposed that the novel identification of electrogenic processes in heterotrophic suspension-cultured cells results from the deployment of electrodes with relatively dilute filling solutions, thus avoiding substantial changes in intracellular ion concentrations.The overwhelming majority of cells in soybean suspension cultures exist in small clusters, and the possibility of intercellular coupling potentially precludes assessment of membrane specific resistance and current density. Furthermore, as with most higher-plant cells, the vacuole occupies a large fraction of the intracellular volume. However, a model in which the measuring electrode is cytosolically located and the cells are electrically well-coupled is the only one which satisfactorily generates values for membrane specific resistance in a manner which is not strongly dependent on the number of cells in the cluster: other models in which the electrode tip is located in the vacuole and-or the impaled cell is electrically isolated from the others do not seem to apply. The measured values of membrane specific resistance are in the range 5.4 to 8.4 omega.m(2), which is in excellent agreement with comparable measurements on other plant and fungal cells. The results are discussed with respect to mechanisms of transmembrane signalling in soybean, as well as to general electrophysiological studies on higher-plant cells in suspension culture and in tissues. PMID- 24212493 TI - Phytochrome - all regions marked by a set of monoclonal antibodies reflect conformational changes. AB - Monoclonal antibodies to defined locations on six regions of the phytochrome molecule (from Avena sativa L. or Zea mays L.) were each found to have a different affinity toward the farred-absorbing form of phytochrome (Pfr) and the red-absorbing form (Pr). The differences were small, but were consistently shown by antibodies which bind to the vicinity of the aminoterminus, the carboxylterminus and to sequences in between. It seems that the conformational differences between Pr and Pfr extend over the whole molecule in as far as it is represented by these regions and the antibodies binding to them. PMID- 24212494 TI - Control of photosynthesis by the carbohydrate level in leaves of the C4 plant Amaranthus edulis L. AB - Photosynthesis was studied in relation to the carbohydrate status in intact leaves of the C4 plant Amaranthus edulis. The rate of leaf net CO2 assimilation, stomatal conductance and intercellular partial pressure of CO2 remained constant or showed little decline towards the end of an 8-h period of illumination in ambient air (340 MUbar CO2, 21% O2). When sucrose export from the leaf was inhibited by applying a 4-h cold-block treatment (1 degrees C) to the petiole, the rate of photosynthesis rapidly decreased with time. After the removal of the cold block from the petiole, further reduction in photosynthetic rate occurred, and there was no recovery in the subsequent light period. Although stomatal conductance declined with time, intercellular CO2 partial pressure remained relatively constant, indicating that the inhibition of photosynthesis was not primarily caused by changes in stomatal aperture. Analysis of the leaf carbohydrate status showed a five- to sixfold increase in the soluble sugar fraction (mainly sucrose) in comparison with the untreated controls, whereas the starch content was the same. Leaf osmotic potential increased significantly with the accumulation of soluble sugars upon petiole chilling, and leaf water potential became slightly more negative. After 14 h recovery in the dark, photosynthesis returned to its initial maximum value within 1 h of illumination, and this was associated with a decline in leaf carbohydrate levels overnight. These data show that, in Amaranthus edulis, depression in photosynthesis when translocation is impaired is closely related to the accumulation of soluble sugars (sucrose) in source leaves, indicating feedback control of C4 photosynthesis. Possible mechanisms by which sucrose accumulation in the leaf may affect the rate of photosynthesis are discussed with regard to the leaf anatomy of C4 plants. PMID- 24212495 TI - Regulation of the appearance of glutamine synthetase in mustard (Sinapis alba L.) cotyledons by light, nitrate and ammonium. AB - During transformation of mustard seedlings cotyledons from storage organs to photosynthetically competent leaves, a process which occurs during the first 4 d after sowing, total glutamine-synthetase (GS, EC 6.3.1.2) activity increases from zero to the high level usually observed in green leaves. In the present study we have used ion-exchange chromatography to separate possible isoforms of GS during the development of the cotyledons. The approach failed since we could only detect a single form of GS, presumably plastidic GS, under all circumstances tested. The technique of selective photooxidative destruction of plastids in situ was applied to solve the problem of GS localization. It was inferred from the data that the GS as detected by ion-exchange chromatography is plastidic GS.The regulatory role, if any, of light, nitrate and ammonium in the process of the appearance of GS in the developing cotyledons was investigated. The results show that nitrate and ammonium play only minor roles. Light, operating via phytochrome, is the major regulatory factor. PMID- 24212496 TI - Short-term water stress leads to a stimulation of sucrose synthesis by activating sucrose-phosphate synthase. AB - The aim of this work was to identify which aspects of photosynthetic metabolism respond most sensitively to leaf water deficit. Spinach (Spinacia oleracea L.) leaf discs were floated on sorbitol concentrations of increasing molarity and changes of the protoplast volume were estimated using [(14)C]sorbitol and (3)H2O penetration. Detached leaves were also wilted until 10% of their fresh weight was lost. Photosynthesis was studied at very high external CO2 concentrations, to eliminate the effect of closing stomata. There was no large inhibition of CO2 fixation after wilting leaves, or until the external water deficit was greater than-1.2 MPa. However, partitioning changed markedly at these moderate water deficits: more sucrose and less starch was made. When an inhibition of CO2 saturated photosynthesis did appear at a water deficit of-2.0 MPa and above, measurements of chlorophyll-fluorescence quenching and metabolite levels showed the thylakoid reactions were not especially susceptible to short-term water stress. The inhibition was accompanied by a small increase of the triose phosphate: ribulose-1,5-bisphosphate ratio, showing regeneration of ribulose-1,5 bisphosphate was affected. However, there was also a general increase of the estimated concentrations of most metabolites, indicating that there is no specific site for the inhibition of photosynthesis. Increasing water deficit led to a large increase of fructose-2,6-bisphosphate. This is explained in terms of a simultaneous increase of fructose-6-phosphate and inorganic phosphate as the cell shrinks. The high fructose-2,6-bisphosphate led to the accumulation of triose phosphates, and the potential significance of this for protection against photoinhibition is discussed. There was an increase in the extractable activity of sucrose-phosphate synthase. This was only detected when the enzyme was assayed in conditions which distinguish between different kinetic forms which have previously been identified in spinach leaves. It is proposed that activation of sucrose-phosphate synthase is one of the first sites at which spinach leaves respond to a rising water deficit. This could be of importance for osmoregulation. PMID- 24212497 TI - High-and low-intensity photosystems in Phycomyces phototropism: Effects of mutations in genes madA, madB, and madC. AB - Sporangiophores of Phycomyces blakesleeanus Burgeff that have been grown in darkness and are then suddenly exposed to unilateral light show a two-step bending response rather than a smooth, monotonic response found in light-adapted specimens (Galland and Lipson, 1987, Proc. Natl. Acad. Sci. USA 84, 104-108). The stepwise bending is controlled by two photosystems optimized for the low-and high intensity ranges. These two photosystems have now been studied in phototropism mutants with defects in genes madA, madB, and madC. All three mutations raise the threshold of the low-intensity (low-fluence) photosystem by about 10(6)-fold and that of the high-intensity (high-fluence) system by about 10(3)-fold. Estimates for the light-adaptation time constants of the low-and high-intensity photosystems show that the mutants are affected in adaptation. In the mutants, the light-adaptation kinetics are only slightly affected in the low-intensity photosystem but, for the high-intensity photosystem, the kinetics are considerably slower than in the wild type. PMID- 24212499 TI - Venous thromboembolism risk in patients with cancer receiving chemotherapy: a real-world analysis. AB - The occurrence of malignant disease increases the risk for venous thromboembolism (VTE). Here we evaluate the risk for VTE in a large unselected cohort of patients with cancer receiving chemotherapy. METHODS: The United States IMPACT health care claims database was retrospectively analyzed to identify patients with a range of solid tumors who started chemotherapy from January 2005 through December 2008. International Classification of Diseases, 9th revision, Clinical Modification Codes were used to identify cancer location, presence of VTE 3.5 months and 12 months after starting chemotherapy, and incidence of major bleeding complications. Health care costs were assessed one year before initiation of chemotherapy and one year after initiation of chemotherapy. RESULTS: The overall incidence of VTE 3.5 months after starting chemotherapy was 7.3% (range 4.6% 11.6% across cancer locations) rising to 13.5% at 12 months (range 9.8%-21.3%). The highest VTE risk was identified in patients with pancreatic, stomach, and lung cancer. Patients in whom VTE developed had a higher risk for major bleeding at 3.5 months and at 12 months (11.0% and 19.8% vs. 3.8% and 9.6%, respectively). Health care costs were significantly higher in patients in whom VTE developed. CONCLUSION: Those undergoing chemotherapy as outpatients are at increased risk for VTE and for major bleeding complications. Thromboprophylaxis may be considered for such patients after carefully assessing the risks and benefits of treatment. PMID- 24212500 TI - HER story: the next chapter in HER-2-directed therapy for advanced breast cancer. AB - Untreated human epidermal growth factor receptor-2 (HER-2)-positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER-2-directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER-2-positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER-2-directed therapy has had on disease outcomes, some patients with HER-2-positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER-2-directed therapy in patients with HER-2 positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER-2-positive ABC outcomes. PMID- 24212501 TI - Endogenous release of female hormones from co-microencapsulated rat granulosa and theca cells. AB - Deficiency of female hormones is the principal cause of menopausal syndrome. The aim of this study was to establish a co-microencapsulation model of ovarian granulosa cells (GCs) and theca cells (TCs), and to investigate its endogenous release of female hormones. Rat ovarian GCs and TCs were isolated and co microencapsulated in alginate-chitosan-alginate microcapsules. The effects of cell number ratio of GCs/TCs on syntheses of estradiol (E2) and progesterone (P4) were investigated in vitro. Serum levels of E2 and P4 in ovariectomized rats were measured for 60 days after the co-microencapsulated GCs and TCs were transplanted. It was showed that E2 synthesis in vitro was influenced by cell number ratio of GCs/TCs and the ratio for the maximum synthesis was 1:2. Serum E2 and P4 levels could be maintained normal for 60 days by the co-microencapsulated GCs/TCs. Transplantation of co-microencapsulated GCs/TCs may be a promising approach to provide endogenous female hormones for menopausal syndrome. PMID- 24212502 TI - The emerging role of TH17 cells in organ transplantation. AB - While transplantation research continues to focus on the development of Treg sparing and plasma cell/B-cell-targeting strategies to improve long-term outcomes, little attention has been paid to the emerging role of the TH17 cell in mediating chronic rejection. This review aimed to summarize the recent emergence of the TH17 and the newly described TH1/17 cell as major players in transplantation and to suggest ways of improving graft outcome through TH17 targeted immunosuppression. PMID- 24212503 TI - Management of renal masses in transplant allografts at an Australian kidney pancreas transplant unit. AB - BACKGROUND: A shift towards partial nephrectomy (PN) in the management of small renal cell carcinoma (RCC) in recent years has prompted a parallel change in the management of rare cases of transplant allograft RCC. There are currently no guidelines on the management of allograft RCC. We present our center experience and review the latest evidence for management of RCC in renal transplant allografts. METHODS: We performed a retrospective review of the transplant patient registry of a kidney-pancreas transplant center between 1984 and 2012. All confirmed allograft kidney RCC cases were included in this series. MEDLINE search of current literature on renal allograft RCC and selection of appropriate studies were conducted. RESULTS: A total of 1,241 patients had received either a living, cadaveric, or combined kidney-pancreas transplant at our center, and four cases of allograft RCC were identified. The first case underwent a radical nephrectomy given the central location of the tumor and his young age. The second case underwent an open PN in the setting of a central tumor with minimal morbidity. The third case involved multiple renal lesions that were subsequently treated with radiofrequency ablation (RFA). The fourth case underwent a non ischemic open PN in the setting of a midpole tumor with minimal morbidity. There have been no cases of local recurrence or metastatic progression at median 21.5 months' follow-up. CONCLUSION: We have shown the safety and efficacy of minimally invasive techniques such as PN and RFA in a variety of tumors. We consider PN as an appropriate therapy for localized, clinical T1 allograft RCC tumors. PMID- 24212504 TI - Fractionating the neural correlates of individual working memory components underlying arithmetic problem solving skills in children. AB - Baddeley and Hitch's multi-component working memory (WM) model has played an enduring and influential role in our understanding of cognitive abilities. Very little is known, however, about the neural basis of this multi-component WM model and the differential role each component plays in mediating arithmetic problem solving abilities in children. Here, we investigate the neural basis of the central executive (CE), phonological (PL) and visuo-spatial (VS) components of WM during a demanding mental arithmetic task in 7-9 year old children (N=74). The VS component was the strongest predictor of math ability in children and was associated with increased arithmetic complexity-related responses in left dorsolateral and right ventrolateral prefrontal cortices as well as bilateral intra-parietal sulcus and supramarginal gyrus in posterior parietal cortex. Critically, VS, CE and PL abilities were associated with largely distinct patterns of brain response. Overlap between VS and CE components was observed in left supramarginal gyrus and no overlap was observed between VS and PL components. Our findings point to a central role of visuo-spatial WM during arithmetic problem-solving in young grade-school children and highlight the usefulness of the multi-component Baddeley and Hitch WM model in fractionating the neural correlates of arithmetic problem solving during development. PMID- 24212505 TI - Biological activity of recombinant bovine interferon tau produced by a silkworm baculovirus gene expression system. AB - Bovine interferon (bIFN) tau plays a crucial role in maternal-fetal recognition and was expressed using a Bombyx mori (Bm) nuclear polyhedrosis virus (silkworm baculovirus) gene expression system. The biological effects of Bm-recombinant bIFNtau (rbIFNtau) on prostaglandin (PG) F2alpha synthesis were investigated in cultured bovine endometrial epithelial cells with oxytocin (OT, 100 nM) and on the in vitro development of bovine embryos. Bm-rbIFNtau and OT were shown to suppress PGF2alpha production in a dose-dependent manner. When in vitro produced morula stage embryos were cultured for 72 hr in modified CR1aa medium supplemented with or without rbIFNtau, Bm-rbIFNtau (10 ng/ml) significantly promoted development to the expanded blastocyst stage. In conclusion, Bm-rbIFNtau was suggested to have the same bioactivity as native IFNtau. PMID- 24212506 TI - Comparative investigation of body composition in male dogs using CT and body fat analysis software. AB - In small animal veterinary practices, body condition score (BCS) is generally used to diagnose obesity. However, BCS does not constitute objective data. In this study, we investigated the value of using human body fat analysis software for male dogs. We also compared changes in body fat after neutering. Changes in body fat at the time of neutering (age 1 year) and 1 year later were compared by performing CT scanning and using human body fat analysis software. We found that body fat increased in all the individuals tested. In terms of the site of fat accumulation, subcutaneous fat was more pronounced than visceral fat with a marked increase on the dorsal side of the abdomen rather than the thorax. PMID- 24212507 TI - Antibiotic resistance in Staphylococcus aureus strains isolated from cows with mastitis in eastern Poland and analysis of susceptibility of resistant strains to alternative nonantibiotic agents: lysostaphin, nisin and polymyxin B. AB - The aim of this study was to analyze the resistance of Staphylococcus aureus isolates from bovine mastitis in the eastern part of Poland to a set of 20 antibiotics and three alternative agents: lysostaphin, nisin and polymyxin B. Eighty-six out of 123 examined isolates were susceptible to all 20 tested antibiotics (70%). The highest percentage of resistance was observed in the case of beta-lactam antibiotics: amoxicillin (n=22, 17.9%), ampicillin (n=28, 22.8%), penicillin (n=29, 23.6%) and streptomycin (n=13; 10.6%). Twenty-five of the penicillin-resistant strains were found to carry the blaZ gene coding for beta lactamases. Two strains were found to be mecA positive and a few strains were classified as multidrug resistant (MDR), one of them was simultaneously resistant to six antibiotics. All strains, resistant to at least one antibiotic (n=37) and two control strains, were susceptible to lysostaphin with MIC values of 0.008-0.5 ug/ml (susceptibility breakpoint 32 ug/ml). Twenty-one (54%) isolates were susceptible to nisin. The MIC value of this agent for 17 (44%) strains was 51.2 ug/ml and was not much higher than the susceptibility breakpoint value (32 ug/ml). Polymyxin B was able to inhibit the growth of the strains only at a high concentration (32-128 ug/ml). The presented results confirmed the observed worldwide problem of spreading antibiotic resistance among staphylococci isolated from bovine mastitis; on the other hand, we have indicated a high level of bactericidal activity of nisin and especially lysostaphin. PMID- 24212508 TI - Lacunar strokes: does shape matter? PMID- 24212509 TI - Cerebrovascular lesions in parkinsonian patients: when do they really matter? PMID- 24212510 TI - Vascular parkinsonism: a case series of 17 patients. AB - OBJECTIVE: To report the clinical and neuroimaging findings in a case series of vascular parkinsonism (VP). METHODS: Seventeen patients with VP were evaluated with motor, cognitive, and neuroimaging standardized tests and scales. RESULTS: All patients had arterial hypertension. Ten patients were male and the mean age of the whole sample was 75.8+/-10.1 years. The mean age of parkinsonism onset was 72.2+/-10.0 years. Common clinical features were urinary incontinence (88.2%), lower limb parkinsonism with freezing of gait and falls (82.3%), and pyramidal signs (76.4%). The mean Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr scores were 72.5+/-21.6 points and 3.3+/-0.9 points, respectively. Sixteen (94.1%) patients had freezing of gait and executive dysfunction. Twelve (70.5%) patients had probable vascular dementia. The mean dose of levodopa was 530.9 mg/day. Unresponsiveness to the drug was confirmed by a 6.9 mean point reduction in the UPDRS score after the "practically defined off" test. CONCLUSION: This series provides a profile of VP with predominant lower-limb involvement, freezing of gait and falls, pyramidal signs, executive dysfunction, concomitant vascular dementia, and poor levodopa response. PMID- 24212511 TI - Mapping the clockworks: what does the Clock Drawing Test assess in normal and pathological aging? AB - The Clock Drawing Test (CDT) is a cognitive screening tool used in clinical and research settings. Despite its role on the assessment of global cognitive functioning, the specific cognitive components required for test performance are still unclear. We aim to assess the role of executive functioning, global cognitive status, visuospatial abilities, and semantic knowledge on Shulman's CDT performance. Fifty-three mild cognitive impairment, 60 Alzheimer's dementia, and 57 normal elderly controls performed the CDT, the Frontal Assessment Battery, the Mini-Mental State Examination, the Stick Design Test, and a naming test (TN-LIN). An ordinal regression assessed specific neuropsychological influences on CDT performance. All the cognitive variables were related to the CDT, accounting for 53% of variance. The strongest association was between the CDT and executive functions, followed by global cognitive status, visuospatial processing, and semantic knowledge. Our result confirms the multidimensional nature of the test and the major role of executive functions on performance. PMID- 24212512 TI - Irregularly shaped lacunar infarction: risk factors and clinical significance. AB - OBJECTIVE: Our study focused on acute lacunar infarct shapes to explore the risk factors and clinical significance of irregularly shaped lacunar infarctions. METHODS: Based on the shape of their acute lacunar infarct, patients (n=204) were classified into the "regular" group or "irregular" group. The characteristics of the lacunar infarction were compared between the regular and irregular groups, between patients with and without neurological deterioration, and between patients with different modified Rankin scale (mRS) scores. The risk factors for irregularly shaped lacunar infarctions, neurological deterioration, and high mRS scores were identified. RESULTS: Blood pressure variability (BPV) was an independent risk factor for irregularly shaped lacunar infarction. Infarction size, prevalence of advanced leukoaraiosis, and irregularly shaped lacunar infarcts were independent risk factors for higher mRS scores. CONCLUSIONS: The irregularly shaped lacunar infarcts were correlated with BPV. Irregularly shaped lacunar infarctions and leukoaraiosis may be associated with unfavorable clinical outcomes. PMID- 24212513 TI - Impact of stroke unit in a public hospital on length of hospitalization and rate of early mortality of ischemic stroke patients. AB - We ascertained whether a public health stroke unit reduces the length of hospitalization, the rate of inpatient fatality, and the mortality rate 30 days after the stroke. METHODS: We compared a cohort of stroke patients managed on a general neurology/medical ward with a similar cohort of stroke patients managed in a stroke unit. The in-patient fatality rates and 30-day mortality rates were analyzed. RESULTS: 729 patients were managed in the general ward and 344 were treated at a comprehensive stroke unit. The in-patient fatality rates were 14.7% for the general ward group and 6.9% for the stroke unit group (p<0.001). The overall mortality rate 30 days after stroke was 20.9% for general ward patients and 14.2% for stroke unit patients (p=0.005). CONCLUSIONS: We observed reduced in patient fatalities and 30-day mortality rates in patients managed in the stroke unit. There was no impact on the length of hospitalization. PMID- 24212514 TI - Nearly one-half of Brazilian patients with multiple sclerosis using natalizumab are DNA-JC virus positive. AB - OBJECTIVE: Natalizumab is a new and efficient treatment for multiple sclerosis (MS). The risk of developing progressive multifocal leukoencephalopathy (PML) during the use of this drug has created the need for better comprehension of JC virus (JCV) infection. The objective of the present study was to assess the prevalence of JCV-DNA in Brazilian patients using natalizumab. METHOD: Qualitative detection of the JCV in the serum was performed with real-time polymerase chain reaction (PCR). RESULTS: In a group of 168 patients with MS who were undergoing treatment with natalizumab, JCV-DNA was detectable in 86 (51.2%) patients. DISCUSSION: Data on JCV-DNA in Brazil add to the worldwide assessment of the prevalence of the JCV in MS patients requiring treatment with natalizumab. PMID- 24212515 TI - Multiple sclerosis starting before the age of 18 years: the Brazilian experience. AB - Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil. PMID- 24212516 TI - Familial adult spinal muscular atrophy associated with the VAPB gene: report of 42 cases in Brazil. AB - Familial spinal muscular atrophy (FSMA) associated with the vesicle-associated membrane protein-associated protein B (VAPB) gene is a rare autosomal dominant disease with late onset and slow progression. We studied 10 of 42 patients from 5 families by taking clinical histories and performing physical exams, electrophysiological studies, and genetic tests. All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex, except two who exhibited brisk reflex. Two patients showed tongue fasciculations and respiratory insufficiency. Electrophysiological studies revealed patterns of lower motor neuron disease, and genetic testing identified a P56S mutation of the VAPB gene. Although it is a rare motor neuron disease, FSMA with this mutation might be much more prevalent in Brazil than expected, and many cases may be undiagnosed. Genetic exams should be performed whenever it is suspected in Brazil. PMID- 24212517 TI - Active extravasation of contrast within the hemorrhage (spot sign): a multidetector computed tomography finding that predicts growth and a worse prognosis in non-traumatic intracerebral hemorrhage. AB - Intracerebral hemorrhage (ICH) causes high rates of disability and neurological sequelae Objective To evaluate spot signs as predictors of expansion and worse prognosis in non-traumatic ICH in a Brazilian cohort. Method We used multidetector computed tomography angiography to study 65 consecutive patients (40 men, 61.5%), with ages varying from 33 to 89 years (median age 55 years). Clinical and imaging findings were correlated with the findings based on the initial imaging. Results Of the individuals who presented a spot sign, 73.7% died (in-hospital mortality), whereas in the absence of a spot sign the mortality rate was 43.0%. Although expansion of ICH was detected in 75% of the patients with a spot sign, expansion was observed in only 9.0% of the patients who did not present a spot sign. Conclusions The spot sign strongly predicted expansion in non-traumatic ICH and an increased risk of in-hospital mortality. PMID- 24212518 TI - Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis. AB - Spine is the primary bone site affected by systemic metastasis. Although there are scales that attempt to manage these patients, their real applicability is unknown. The Tokuhashi Scoring System (TSS) is a widely used prognostic tool. At the time of treatment, the data necessary to complete TSS may be incomplete, making its application impossible. Objective To evaluate the number of TSS scores completed by the time the clinical therapeutic decision was made. Methods From July 2010 to January 2012, we selected patients who were diagnosed with spinal metastases. Results Sixty spinal metastasis patients (21 female, 39 male) were evaluated between July 2010 and January 2012. At the time of the treatment decision, only 25% of the patients had completed the TSS items. Conclusion In the majority of patients with vertebral metastasis, TSS variables cannot be applied. PMID- 24212519 TI - Experimental model of intracranial hypertension with continuous multiparametric monitoring in swine. AB - OBJECTIVE: Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI). Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments. METHODS: We describe a new experimental porcine model designed to simulate expansive brain hematoma causing IH. Under anesthesia, IH was simulated with a balloon insufflation. The IH variables were measured with intracranial pressure (ICP) parenchymal monitoring, epidural, cerebral oximetry, and transcranial Doppler (TCD). RESULTS: None of the animals died during the experiment. The ICP epidural showed a slower rise compared with parenchymal ICP. We found a correlation between ICP and cerebral oximetry. CONCLUSION: The model described here seems useful to understand some of the pathophysiological characteristics of acute IH. PMID- 24212520 TI - Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy. AB - It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP). On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP. PMID- 24212521 TI - Traumatic injuries of peripheral nerves: a review with emphasis on surgical indication. AB - Traumatic peripheral nerve injury is a dramatic condition present in many of the injuries to the upper and lower extremities. An understanding of its physiopathology and selection of a suitable time for surgery are necessary for proper treatment of this challenging disorder. This article reviews the physiopathology of traumatic peripheral nerve injury, considers the most used classification, and discusses the main aspects of surgical timing and treatment of such a condition. PMID- 24212522 TI - Jean-Martin Charcot, father of modern neurology: an homage 120 years after his death. AB - Jean-Martin Charcot was a pioneer in a variety of subjects, including nervous system diseases; anatomy; physiology; pathology; and diseases of ageing, joints, and lungs. His medical achievements were mainly based on his anatomopathological proficiency, his observation, and his personal thoroughness that favored the delineation of the nosology of the main neurological diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, peroneal muscular atrophy, and hysteria/epilepsy. The link of this anatomoclinical method with iconographic representations and theatrical lessons, and the rich bibliographical documentations, carried out in a crowded barn for diseased people--Salpetriere Hospital, were the basis of his achievements, which are still discussed 120 years after his death. PMID- 24212523 TI - French school of neurology in the 19th and first half of the 20th century, and its influence in Brazil. AB - French medicine was of the utmost importance for the birth of modern medicine and neurology in the 19th century. Innovative approaches, such as examination at the bedside, the use of the stethoscope, techniques of auscultation, palpation, and close patient examination, besides emphasis on anatomical-clinical correlation and observation of the outcome of the disease, were put into practice. French medicine offered professional training and incentives for the beginnings of Brazilian neurology and psychiatry. Returning from France, many Brazilian physicians implemented what they had learned, mainly in Paris. The most important pupils of the French neurology schools in Brazil during the 19th century and first half of the 20th century include names like Antonio Austregesilo, Aloysio de Castro, Enjolras Vampre, and Deolindo Couto, founders of the leading Brazilian neurological schools, directly influenced by Dejerine, Pierre Marie, Guillain and Babinski. PMID- 24212524 TI - Spinal cavernous angioma complicated by hemorrhage: susceptibility-weighted imaging findings. PMID- 24212525 TI - Armored brain. PMID- 24212526 TI - "Hot cross bun" sign resembling multiple system atrophy in a patient with Machado Joseph disease. PMID- 24212527 TI - Brain involvement in H7N9 bird flu: a topic for consideration. PMID- 24212531 TI - Probing morphological changes in polymersomes with magnetic birefringence. AB - Magnetic birefringence was used for in situ monitoring of the morphological changes in diamagnetic polymersomes during shape-transformation by dialysis. The birefringence was found to be very sensitive to the polymersome morphology, as determined by electron microscopy. The deflation of polymersomes into disks was observed, followed by a bending and partial inflation into stomatocytes. PMID- 24212528 TI - Is it correct for a woman with multiple sclerosis to forgo medication because she may become pregnant? PMID- 24212532 TI - Lighting up thiolated Au@Ag nanoclusters via aggregation-induced emission. AB - A simple strategy has been developed to synthesize highly luminescent thiolated Au@Ag nanoclusters (NCs) by using Ag(i) ions to bridge small Au(i)-thiolate motifs on the weakly luminescent thiolated Au NCs, leading to the formation of large Au(i)/Ag(i)-thiolate motifs on the NC surface and thus generating strong luminescence via aggregation-induced emission. PMID- 24212534 TI - Characterization of aerobic and facultative anaerobic bacteria from the liquid phase of an anaerobic fixed-bed digester treating a cheese whey substrate. AB - Bacterial counts on the liquid phase of an anaerobic, fixed-bed digester, treating a deproteinated, prefermented cheese whey substrate, were conducted on two different media under aerobic and facultative conditions. Average counts of 16.6*10(6) and 26.5*10(6) ml(-1) were obtained on the two media, with the nutritionally poorer of the two media giving the highest average count. Seventy five isolates from both media, incubated aerobically as well as in anaerobic jars, were obtained. These isolates as well as 13 reference strains were phenotypically characterized. The similarities between cultures were calculated using the similarity coefficient of Sokal and Michener [16]. The organisms were clustered using the unweighted pair group method, and the results presented as a simplified dendrogram. The isolates could be divided into 3 main groups: gram negative fermentative rods, mainlyEnterobacter, Klebsiella, andCitrobacter, withKlebsiella as the predominant genus; gram-positive bacteria, mainly enterococci; and gram-negative nonfermentive rods of the generaPseudomonas, Alcaligenes, andAcinetobacter. All the enterobacteria and enterococci were able to produce acetic acid, an intermediate in methanogenesis. PMID- 24212533 TI - Osteoarthritis pain has a significant neuropathic component: an exploratory in vivo patient model. AB - Osteoarthritis is the most common form of arthritis and includes manifestations of both nociceptive and neuropathic mechanisms. Intravenous lignocaine, a sodium channel blocker and neuronal membrane stabiliser, has been shown in controlled trials to be effective in neuropathic pain; however, the outcome of intravenous lignocaine in osteoarthritis patients has not been assessed yet. The existence of a neuropathic component to the pain of osteoarthritis was investigated by examining possible benefits upon sensory aspects of pain in osteoarthritis patients receiving intravenous lignocaine therapy. Retrospective observational study was carried out using health data routinely collected for non-research purposes. Patients with generalised osteoarthritis who had not responded to more conservative treatments were recruited sequentially and scheduled for intravenous lignocaine therapy either in the rheumatology or pain relief departments. Assessment of efficacy was carried out through a questionnaire including sensory, psychological and social aspects of pain. The sample consisted of 17 women (60.7%) and 11 men (39.3%) with an average age at the time of treatment of 59 +/- 11 years. The average pain relief calculated from the NRS scores was 30.2 +/- 21.4%, and the mean duration of pain relief was 10 +/- 6 weeks. Pain intensity (p < 0.001), pain relief (p < 0.003) and mobility (p < 0.003) were all significantly improved after administration of lignocaine intravenous infusion therapy. Pain was significantly reduced in a group of osteoarthritis patients after administration of intravenous lignocaine. This suggests that part of the pain mechanism in this patient group may be neuropathic, appears to contribute significantly to the patients' pain, and requires further investigation in studies designed specifically for the purpose. PMID- 24212535 TI - Unusual microorganisms observed in New Zealand hot springs. AB - A technique is described for studying hot spring microbial morphotypes by using electron microscope grids incubatedin situ. Such studies revealed the presence of filaments bearing swollen saclike structures in a number of New Zealand hot springs. There was considerable variation in the size, structure, and morphology of the filaments and the saclike structures. PMID- 24212536 TI - A method for enumerating protozoa in a variety of freshwater habitats. AB - A method for enumerating protozoa (ciliates, flagellates, and amoebae) in fine, freshwater sediments is described. The results, using fixed material, are compared with two published techniques: a culture method (most probable number) and a direct count method. PMID- 24212537 TI - Relationship between microbial activity of stream sediments, determined by three different methods, and abiotic variables. AB - Microbial activity of stream sediments has been determined by three distinct methods: phosphatase levels, maximum uptake velocity of radiolabeled glucose, and carbon dioxide production rates. These methods have been applied to different types of sediment (mud, sand, gravel) from the same stream and to 5 samples from two different streams for comparison. Temperature, discharge, and 8 other abiotic variables for each sample were also determined. The 3 activity methods correlated closely with each other and were measured with a similar precision. Phosphatase activity could be predicted for all sites from bulk density. The largest proportion of the variance associated with carbon dioxide production was explained by variations in percent of organic matter, but the relationship did not hold for all streams. Maximum uptake velocity, compared with the other 2 activity measurements, was poorly explained by any of the abiotic variables. PMID- 24212538 TI - Distribution of microorganisms, total biomass, and enzyme activities in different particles of brown soil. AB - A soil sample from the Ap horizon of an arable brown soil was fractionated by wet sieving, and seven size fractions of organic and mineral soil particles were separated. The organic fractions formed only 2.2% of the soil dry mass, but contained 41.5 and 29.12% of the total soil content of carbon and nitrogen, respectively, and thus represented an important reservoir of readily utilizable nutrients. Organic particles also accumulated most of the soil enzyme activities, determined asbeta-glucosidase,beta-acetylglucosaminidase, and proteinase activity. The highest counts of bacteria, actinomycetes, and fungi per gram of the soil fractions were obtained with the organic particles, but for the most part microorganisms accumulated in the silt-clay fraction. All soil fractions except the coarsest organic particles contained higher counts of oligotrophic bacteria than copiotrophic ones. Microbial counts, ATP contents, and enzyme activities decreased significantly with decrease in size of the organic soil particles, and increased with decrease in size of the mineral soil particles. Thus, the coarse organic particles >5 mm and the silt-clay fraction <0.05 mm represent the sites with the highest concentrations of microorganisms, ATP contents, and enzyme activities in the arable brown soil under test. PMID- 24212539 TI - Effects of moisture on soil microorganisms and nematodes: A field experiment. AB - The effects of soil moisture changes on bacteria, fungi, protozoa, and nematodes and changes in oxygen consumption were studied in a field experiment. In one plot the soil was drip-irrigated daily for 10 days, while an adjacent plot experienced one rainfall and was then allowed to dry out. Oxygen consumption was the parameter measured which responded most rapidly to changes in soil moisture content. Lengths of fluorescein diacetate-active hyphae paralleled oxygen consumption in both plots. Total hyphal length was not affected by one rainfall but increased from 700 mg(-1) dry weight soil to more than 1,600 m in less than 10 days in the irrigated plot. In the rain plot, bacterial numbers doubled within 3 days and declined during the following period of drought. In the irrigated plot, numbers increased by 50% and then remained constant over the duration of the study. Only small changes in protozoan numbers were observed, with the exception of the last sampling date in the irrigated plot when large numbers of naked amoebae were recorded 2 days after a large natural rainfall. Nematode numbers, especially obligate root feeders, increased in both treatments. The increases were caused by decoiling rather than growth. The results indicate that fungal respiration was dominating, while bacteria, lacking a suitable source of energy, were less active, except for the first days. PMID- 24212540 TI - Enteric luminous microflora of the pond-cultured milk fishChanos chanos (Forskal). AB - Qualitative and quantitative investigations were made on the luminous bacteria associated with the gut of pond cultured milk fishChanos chanos. Significant differences in luminous bacterial numbers were found between gut and pond water and between gut and pond sediment, but not between pond water and sediment. No significant variation in luminous bacterial population among the gut regions was observed. The quantity of ingesta in the fish gut does not appear to influence the biomass of luminous bacteria.Vibrio harveyi andV. fischeri were the 2 most commonly encountered species, and of the 2 luminous species,V. harveyi was predominant. PMID- 24212541 TI - Quantification of different yeasts associated with the bark beetle,Ips typographus, during its attack on a spruce tree. AB - There were different amounts and types of yeasts associated with individuals ofIps typographus spruce bark beetles during different phases of their attack on a healthy spruce tree. The yeasts were isolated on Sabouraud agar medium in order to identify them and estimate their numbers.Hansenula holstii andCandida diddensii type yeasts were most frequently isolated. The increase in number of these two yeast types probably accounted for most of the total yeast increase found during the later attack phases of the bark beetles. Lesser amounts ofHansenula capsulata, Pichia pinus, Candida nitratophila, and twoCryptococcus type yeasts were also found. PMID- 24212542 TI - Prediction of severe cardiac involvement by fundus lesion in sarcoidosis. AB - PURPOSE: We examined the relation between ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation. METHODS: In this retrospective, observational, cross-sectional study, we reviewed the clinical records of 108 patients diagnosed with ocular sarcoidosis based on new diagnostic criteria established in Japan. We examined and compared the relationship between fundus findings of ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation. RESULTS: Of 108 patients with ocular sarcoidosis, seven patients (6.5 %) with median age of 61 years (interquartile range 59-63 years) also had severe heart disease leading to implantation of a pacemaker. Median duration of ocular symptoms was 4.5 years (interquartile range 3.6-7.8 years). Of seven patients with severe cardiac involvement, six had multiple peripheral chorioretinal atrophic lesions (MPCAL), two had nodules in the angle and tent like peripheral anterior synechia, and two had snowball vitreous opacity. The prevalence of atrophic MPCAL lesions was significantly higher than that of other ocular findings (P < 0.05). CONCLUSIONS: In patients with concurrent ocular sarcoidosis and severe cardiac sarcoidosis, MPCAL atrophic lesions were observed significantly more frequently, suggesting that severe cardiac involvement may be predicted by specific fundus lesions. PMID- 24212543 TI - Loading and transport of assimilates in different maize leaf bundles : Digital image analysis of (14)C-microautoradiographs. AB - The loading and transport functions of vascular bundles in maize (Zea mays L.) leaf strips were investigated by microautoradiography after application of (14)CO2. The concentrations of (14)C-contents in thin-walled sieve tubes of individual bundles in the loading and transport regions were determined by digital image analysis of silver-grain density over the sieve tubes and compared. In the loading region, relatively high concentrations of (14)C-contents were found in the thin-walled sieve tubes of small bundles and in the small, thin walled sieve tubes of the intermediate bundles; the concentration of (14)C-label in large bundles was very low. In the transport region, at a transport distance of 2 cm, all of the small bundles contained (14)C-assimilates, but generally less than the same bundles did in the loading region; by comparison, at that distance intermediate and large bundles contained two-to threefold more (14)C-assimilates than the same bundles in the loading region. The lateral transfer of assimilates from smaller to larger bundles via transverse veins could be demonstrated directly in microautoradiographs. A reverse transport from larger to smaller bundles was not found. At a transport distance of 4 cm, all large and intermediate bundles were (14)C-labeled, but many of the small bundles were not. Although all longitudinal bundles were able to transport (14)C-asimilates longitudinally down the blade, it was the large bundles that were primarily involved with longitudinal transport and the small bundles that were primarily involved with loading. PMID- 24212544 TI - Developmental changes and tissue distribution of lectin in Tulipa. AB - A sensitive enzyme-immunoassay was developed to quantify the tulip lectin and used to follow its distribution during the life cycle of tulips cv. Attila.The tulip lectin is predominantly located in the bulbs. At planting time the absolute lectin concentration is approximately the same in all bulb scales. However, as the shoot grows and the plant turns on to flowering, the lectin concentration rapidly decreases, first in the inner bulb scales but later also in the outer bulb scale. Soon after flowering the lectin rapidly accumulates in the new daughter bulbs.Lectin levels in leaves, stems and flowers are very low. The lectin in these tissues is already present before the sprout emerges. During the first two weeks after planting, there is a small increase in lectin concentration, followed by a rapid decrease as the plant turns on to flowering. By flowering time all the lectin has disappeared from the aerial parts. PMID- 24212545 TI - Evidence for a plasma-membrane-bound nitrate reductase involved in nitrate uptake of Chlorella sorokiniana. AB - Anti-nitrate-reductase (NR) immunoglobulin-G (IgG) fragments inhibited nitrate uptake into Chlorella cells but had no affect on nitrite uptake. Intact anti-NR serum and preimmune IgG fragments had no affect on nitrate uptake. Membrane associated NR was detected in plasma-membrane (PM) fractions isolated by aqueous two-phase partitioning. The PM-associated NR was not removed by sonicating PM vesicles in 500 mM NaCl and 1 mM ethylenediaminetetraacetic acid and represented up to 0.8% of the total Chlorella NR activity. The PM NR was solubilized by Triton X-100 and inactivated by Chlorella NR antiserum. Plasma-membrane NR was present in ammonium-grown Chlorella cells that completely lacked soluble NR activity. The subunit sizes of the PM and soluble NRs were 60 and 95 kDa, respectively, as determined by sodium-dodecyl-sulfate electrophoresis and western blotting. PMID- 24212546 TI - Calcium requirement of phytochrome-mediated fern-spore germination: No direct phytochrome-calcium interaction in the phytochrome-initiated transduction chain. AB - Phytochrome-mediated germination of fern spores of Dryopteris paleacea Sw. was initiated by a saturating red-light (R) irradiation after 20 h of imbibition. For its realization external Ca(2+) was required, with a threshold at a submicromolar concentration, and an optimum was reached around 10(-4) M. At concentrations >=10(-1) M only a reduced response was obtained, based probably on an unspecific osmotic or ionic effect. The germination response was inhibited by La(3+), an antagonist of Ca(2+). From these results it is concluded that Ca(2+) influx from the medium into the spores may be an important event in phytochrome-mediated germination. In the absence of Ca(2+) the R-stimulated system remained capable of responding to Ca(2+), added as late as 40 h after R. Moreover, Ca(2+) was effective even if added after the active form of phytochrome, Pfr, had been abolished by far-red (FR) 24 h after R. Thus, the primary effect of Pfr, that initiates the transduction chain, does not require calcium. "Coupling" of Pfr to subsequent dark reactions has been investigated by R-FR irradiations with various dark intervals. The resulting "escape kinetics" were characterized by a lag phase (6 h) and half-maximal escape from FR reversibility (19 h). These kinetics were not significantly changed by the presence or absence of calcium. Thus, direct interaction of Pfr and calcium is not a step in the transduction chain initiated by the active form of photochrome. PMID- 24212547 TI - Effects of white, blue, red light and darkness on pH of the apoplast in the Samanea pulvinus. AB - Leaflet movements in Samanea saman (Jacq.) Merrill are driven by fluxes of K(+), anions, and water through membranes of motor cells in the pulvinus (R.L. Satter et al., 1974, J. Gen. Physiol. 64, 413-430). Extensor cells take up K(+) and swell in white light (WL) while flexor cells take up K(+) and swell in darkness (D). Excised strips of extensor and flexor motor tissue acidify their bathing medium under conditions that normally promote increase in K(+) in the intact tissue, and alkalize the medium under conditions that normally induce decrease in K(+) (A. Iglesias and R.L. Satter, 1983, Plant Physiol. 72, 564). To obtain information on pH changes in the whole pulvinus, we measured effects of light on pH of the apoplast, using liquid membrane microelectrodes sensitive to H(+). We report the following: (1) The pH of the extensor apoplast was higher than that of the flexor apoplast in WL and in D (pH gradient of 1.0 units in WL and 2.0 units in D). Apoplastic pH might affect K(+) transport through the plasma membranes of Samanea motor cells, since the conductance, gating, and selectivity of ionic channels in other systems depend upon external pH. (2) Extensor cells acidified and flexor cells alkalized their environment in response to irradiation with WL, while the reverse changes occurred in response to D. These results are consistent with the results of Iglesias and Satter (1983), and support the physiological relevance of data obtained with excised tissue. (3) The pH changes in response to irradiation with red light were similar to those obtained with D; also, the pH changes in response to blue light were similar to those obtained with WL. The pulvinus closed in red light as in darkness and opened in WL, but failed to open in blue light. The advantages and limitations of apoplastic pH measurements for assaying H(+) transport are discussed. PMID- 24212548 TI - Biosynthesis of legume-seed galactomannans in vitro : Cooperative interactions of a guanosine 5'-diphosphate-mannose-linked (1->4)-beta-D-manno-syltransferase and a uridine 5'-diphosphate-galactose-linked alpha-D-galactosyltransferase in particulate enzyme preparations from developing endosperms of fenugreek (Trigonella foenum-graecum L.) and guar (Cyamopsis tetragonoloba [L.] Taub.). AB - Particulate enzyme preparations were isolated from developing fenugreek (Trigonella foenum-graecum L.) and guar (Cyamopsis tetragonoloba [L.] Taub.) seed endosperms during the period of galactomannan deposition in vivo. These preparations catalysed the formation of polysacharide products from guanosine 5' diphosphate (GDP)-mannose, from uridine 5'-diphosphate (UDP)-galactose and from mixtures of the two nucleotides. The products were analysed by solubility, by complete acid hydrolysis, and by selective enzymatic cleavage using pure enzymes of known specificity. With GDP-[U-(14)C]-D-mannose as substrate and a divalent metal cation (Mg(+2), Mn(+2), or Ca(+2)) a highly efficient transfer of labelled D-mannosyl residues was obtained to give a product identified as linear (1->4) beta-linked D-mannan. No transfer of galactosyl residues was obtained when GDP-[U (14)C]-D-galactose was the only substrate, although very low and variable amounts of an unidentified product which released labelled glucose on acid hydrolysis were formed. In the presence of UDP-galactose, GDP-mannose and Mn(+2) ions, products were formed which have been characterised as galactomanans - a linear (1 >4)-beta-D-mannan backbone carrying D-galactopyranosyl substituents linked (1->6) alpha to mannose. The degree of galactose substitution of the D-mannan backbone was manipulated in vitro by varying GDP-mannose concentrations at constant (saturating) UDP-galactose levels. The transfer of D-galactosyl residues from UDP galactose to galactomannan was absolutely dependent upon the simultaneous transfer of D-mannosyl residues from GDP-mannose. D-Mannan sequences pre-formed in situ using the mannosyltransferase in the absence of UDP-galactose could not become galactose-substituted in a subsequent incubation either with UDP-galactose alone or with UDP-galactose plus GDP-mannose A model for the interaction of GDP mannose mannosyltransferase and UDP-galactose galactosyltransferase in galactomannan biosynthesis is proposed. PMID- 24212549 TI - Substrate specifity of the hexose carrier in the plasmalemma of Chenopodium suspension cells probed by transmembrane exchange diffusion. AB - Substrate specifity of the proton-driven hexose cotransport carrier in the plasmalemma of photoautotrophic suspension cells of Chenopodium rubrum L. has been studies through the short-term perturbation of (14)C-labelled efflux of 3-O methyl-D-glucose. Efflux, occurring exclusively via carrier-mediated exchange diffusion, is trans-stimulated by the substrate and trans-inhibited by the glucose-transport inhibitors phlorizin (K 1/2=7.9 mM) and its aglucon phloretin (K 1/2=84 MUM); with both inhibitors, 3-O-methyl-D-glucose efflux may be blocked completely. Trans-stimulation of efflux (up to fourfold) by a variety of the D enantiomers of neutral hexoses, including glucose (K 1/2=48 MUM), 3-O-methyl-D glucose (K 1/2=139 MUM), and fructose (K 1/2=730 MUM), but not by, for instance, D-allose, and L-sorbose, shows that carrier-substrate interaction critically involves the axial position at C-1 and C-3, respectively. We suggest that substrate binding by the Chenopodium hexose carrier involves both hydrophobic interaction with the pyran-ring and hydrogen-ion bonding at C-1 and C-3 of the D glucose conformation. PMID- 24212550 TI - The effect of chemical stress on the polypeptide composition of the intercellular fluid of barley leaves. AB - The effect of chemical stress on the polypeptide composition of the intercellular fluid of barley (Hordeum vulgare L.) and tomato (Lycopersicon esculentum Mill.) leaves has been studied. In some dicotyledonous plant species, including tomato, exposure to chemical stress leads to the denovo synthesis of intercellular proteins known as pathogenesis-related proteins which have been implicated to be part of a defence mechanism. In barley, however, no such changes in the polypeptide composition of the intercellular fluid could be detected. On the other hand, similar stress conditions induce in barley a strong accumulation of mRNA encoding leaf-specific thionins. These barley thionins represent a novel class of cell-wall proteins toxic to phytopathogenic fungi and are possibly involved in the defence mechanism. These proteins could not be detected in tomato plants. In contrast to the pathogenesis-related proteins of dicotyledonous plants, the leaf-specific thionins of barley are not present in the intercellular fluid of leaves. These results indicate that barley may have evolved a different mechanism to cope with the presence of stress. PMID- 24212551 TI - Chloroplast gene expression in lettuce grown under different irradiances. AB - Chloroplast DNA sequences have been used as hybridisation probes to measure the levels of RNA transcripts present in low- and high-light-grown lettuce (Lactuca sativa L.) plants. The transcript levels for rbc L, psa A, psb A and rDNA are not different between these two light regimes. In contrast, transcript levels for atp BE and pet BD are increased in high-light as a proportion of the chloroplast RNA. Three days after transfer from low-light into high-light, increased transcript levels were found for atp BE, although no change was detected for the psa A or psb A transcripts. In addition, young plants in high-light contain twofold more chloroplast RNA per unit chlorophyll than do low-light plants of equivalent age. Therefore, in these young high-light plants the absolute transcript levels per unit chlorophyll are much greater. With increasing leaf age the RNA per chlorophyll becomes similar for both light conditions. These results are discussed in relation to the photoregulation of chloroplast-encoded gene expression. PMID- 24212552 TI - Regulation by light and ethanol of the synthesis of the light-harvesting chlorophyll a/b-binding protein of photosystem II in Euglena. AB - In dark-grown Euglena, a single 122-kdalton (kDa) precursor to the light harvesting chlorophyll a/b-binding protein of photosystem II (pLHCPII) was synthesized at a very low rate and LHCPII synthesis was undetectable as determined by pulse-labeling with [(35)S]sulfate and immunoprecipitation with a specific antibody against Euglena LHCPII. Synthesis of a 207-, 161-, 122- and 110 kDa pLHCPII was detected after light exposure, with the 207-kDa pLHCPII being the most abundant pLHCPII synthesized. The rate of synthesis of all four pLHCPIIs and the 25.6-kDa and 27.2-kDa LHCPIIs increased in the first 12-24 h of light exposure and then declined. The maximal rate of LHCPII synthesis in the light was 50-100-fold greater than the rate in darkness. Addition of ethanol at the time of light exposure inhibited LHCPII synthesis, indicating that induction is catabolite-sensitive. The halflife of pLHCPII in the light or in darkness was 20 min. Therefore, the light induction of LHCPII is the result of an increased rate of synthesis rather than a decreased rate of degradation. Transfer of illuminated cells to darkness resulted in an 80% decrease in the rate of pHLCPII synthesis during the first 0.5 h. Illuminated cells returned to darkness continued to synthesize both 207-kDa pLHCPII and LHCPII for at least 5 h. Light exposure or ethanol addition did not increase the level of translatable RNA for LHCPII. The 50-100-fold catabolite-sensitive increase in the rate of LHCPII synthesis in the absence of a concomitant increase in the level of translatable RNA for LHCPII indicates that in Euglena, the synthesis of LHCPII is controlled at the translational rather than at the transcriptional level. PMID- 24212553 TI - Gas exchange of ears of cereals in response to carbon dioxide and light : I. Relative contributions of parts of the ears of wheat, oat, and barley to the gas exchange of the whole organ. AB - One cultivar each of spring wheat (Triticum aestivum L. cv. Arkas), oat (Avena sativa L. cv. Lorenz), and barley (Hordeum vulgare L. cv. Aramir) was chosen in order to study the relative contributions of individual bracts to the gas exchange of whole ears. The distribution and frequency of the stomata on the bracts were examined. Gas exchange was measured at normal atmospheric CO2 (330 MUbar) and at high CO2 (2000 MUbar) on intact ears and on ears from which glumes or lemmas and pleae (wheat and oat) or awns (barley) had been removed.The relative contribution to the gas exchange of the whole organ is highest for the awns of barley ears. In wheat, the contribution of the glumes is slightly higher than that of the inner bracts before anthesis. Two weeks after anthesis the inner bracts contribute more than the glumes. This tendency of increasing importance of the inner bracts is also found in oat ears, but the relative amount of CO2 uptake by the glumes is higher than in wheat. These changes during ontogeny result from the better supply of light to the inner bracts caused by opening of the ears' structures during grain filling, which in part compensates for the decreasing photosynthetic capacity.The ratio of the photosynthesis rate at high CO2 to that at normal CO2 is lower for the glumes of oat and for the awns of barley than for the other bracts. PMID- 24212554 TI - Tip-localised H(+)-fluxes and the applicability of the acid-growth hypothesis to tip-growing cells: Control of chloronemal extension in Funaria hygrometrica by auxin and light. AB - The role of tip-localised H(+) secretion in regulating chloronemal tip growth in the moss Funaria hygrometrica Hedw. was investigated. pH was monitored with pH microelectrodes placed close to the cell surface while the rate of extension growth was manipulated by illumination and by the application of indole-3-acetic acid. Growth stimulations were accompanied by acidification of the external solution; this acidification was most pronounced at the growing tip. The timing and extent of acification external to the tip correlated well with the magnitude and time course of growth stimulations. The maintenance of both growth and H(+) efflux under CO2-free conditions indicated that neither photosynthetic nor respiratory CO2 metabolism were involved. Artificially acidifying the nutrient solution rapidly but transiently stimulated elongation in both white light and darkness. Furthermore, the stimulation of elongation caused by white light was inhibited if the nutrient solution was buffered strongly near neutrality. We conclude that the "acid growth" hypothesis is applicable to tip growth in Funaria and that light and exogenous indole-3-acetic acid act at least in part by stimulating localised H(+)-ion efflux. PMID- 24212555 TI - Differential regulation by phytochrome of the appearance of plastidic and cytoplasmatic isoforms of glutathione reductase in mustard (Sinapis alba L.) cotyledons. AB - An increase of glutathione reductase (GR; EC 1.6.4.2) activity during the transformation of mustard (Sinapis alba L.) cotyledons from storage organs to photosynthetically competent leaves was previously found to be controlled by light acting via phytochrome (Drumm, H., Mohr, H., Z. Naturforsch. 28c 559-563, 1973). Two isoforms of GR could be separated by disc electrophoresis. In the present study we have applied ionexchange chromatography to separate isoforms of GR during the development of the cotyledons. Furthermore, the technique of in situ photooxidation of plastids was used to distinguish between plastidic and cytoplasmatic isoforms. The isoform GR2 is the plastidic enzyme, as shown by its sensitivity to photooxidative treatment, while GR1 is a cytoplasmatic protein not affected by photooxidative treatment of plastids. Both isoforms are promoted by phytochrome but with different time courses. The appearance of GR1 is independent of the integrity of the plastids, as one might expect. However, unexpectedly, the phytochrome-mediated re-appearance of GR2 after a photooxidative treatment is much less affected by photooxidative destruction of the plastids, i.e. by the lack of a particular "plastidic factor", than was to be expected from previous experience with typical plastidic proteins. An interpretation of this finding must await measurements at the level of GR2 mRNA. PMID- 24212556 TI - Reduced-activity mutants of phosphoglucose isomerase in the cytosol and chloroplast of Clarkia xantiana : II. Study of the mechanisms which regulate photosynthate partitioning. AB - (i) We have studied the influence of reduced phosphoglucose-isomerase (PGI) activity on photosynthetic carbon metabolism in mutants of Clarkia xantiana Gray (Onagraceae). The mutants had reduced plastid (75% or 50% of wildtype) or reduced cytosolic (64%, 36% or 18% of wildtype) PGI activity. (ii) Reduced plastid PGI had no significant effect on metabolism in low light. In high light, starch synthesis decreased by 50%. There was no corresponding increase of sucrose synthesis. Instead glycerate-3-phosphate, ribulose-1,5-bisphosphate, reduction of QA (the acceptor for photosystem II) and energy-dependent chlorophyll fluorescence quenching increased, and O2 evolution was inhibited by 25%. (iii) Decreased cytosolic PGI led to lower rates of sucrose synthesis, increased fructose-2,6-bisphosphate, glycerate-3-phosphate and ribulose-1,5-bisphosphate, and a stimulation of starch synthesis, but without a significant inhibition of O2 evolution. Partitioning was most affected in low light, while the metabolite levels changed more at saturating irradiances. (iv) These results provide decisive evidence that fructose-2,6-bisphosphate can mediate a feedback inhibition of sucrose synthesis in response to accumulating hexose phosphates. They also provide evidence that the ensuing stimulation of starch synthesis is due to activation of ADP-glucose pyrophosphorylase by a rising glycerate-3 phosphate: inorganic phosphate ratio, and that this can occur without any loss of photosynthetic rate. However the effectiveness of these mechanisms varies, depending on the conditions. (v) These results are analysed using the approach of Kacser and Burns (1973, Trends Biochem. Sci. 7, 1149-1161) to provide estimates for the elasticities and flux-control coefficient of the cytosolic fructose-1,6 bisphosphatase, and to estimate the gain in the fructose-2,6-bisphosphate regulator cycle during feedback inhibition of sucrose synthesis. PMID- 24212557 TI - Putrescine and putrescine N-methyltransferase in the biosynthesis of tropane alkaloids in cultured roots of Hyoscyamus albus : I. Biochemical studies. AB - The activity of arginine decarboxylase (EC 4.1.1.19) in cultured roots of Hyoscyamus albus L., which produce considerable amounts of tropane alkaloids, was twice that of ornithine decarboxylase (EC 4.1.1.17), both activities being highest during active root growth, whereas arginase (EC 3.5.3.1) activity was negligible. Actively growing roots had putrescine conjugates as their major polyamines, and spermidine was the most abundant free polyamine. Putrescine N methyltransferase (PMT; EC 2.1.1.53) activity was high, the peak occurring on the sixth day of culture when root growth became slower. Thereafter, the free N methylputrescine content of the roots increased and was followed by an increase in alkaloid content (mostly hyoscyamine). The amounts of arginine and, especially, of ornithine were low. No N-methylornithine was detected. The PMT activity was present only in root, shoot and cell-suspension cultures of plants that synthesized tropane alkaloids or nicotine; no enzyme activities that methylate ornithine at the delta-amino group or that decarboxylate delta-N methylornithine were detected in any of the cultures tested. Our data indicate that tropane alkaloids in H. albus roots are synthesized by way of the symmetrical putrescine, i.e. a pathway different from that proposed by E. Leete (1962, J. Am. Chem. Soc. 84, 55) according to which these alkaloids are synthesized by way of asymmetrical delta-N-methylornithine. PMID- 24212558 TI - Putrescine and putrescine N-methyltransferase in the biosynthesis of tropane alkaloids in cultured roots of Hyoscyamus albus : II. Incorporation of labeled precursors. AB - [1,4-(14)C]Putrescine, administered to cultured roots of Hyoscyamus albus L., was converted to spermidine and spermine as well as to conjugated forms. A substantial fraction of its radioactivity (approx. 6%) was, however, incorporated into N-methylputrescine within 4 h, followed by an increase in radioactive tropane alkaloids (mostly hyoscyamine). Incubation of the roots with DL-[5 (14)C]ornithine and L-[2,3-(3)H]arginine separately resulted in rapid incorporation of each label into free putrescine and N-methylputrescine, followed by incorporation into hyoscyamine. During active alkaloid biosynthesis in H. albus roots, scarcely any radioactivity was recovered in delta-N-methylornithine. When the roots had been treated with 5 mM DL-alpha-difluoromethylornithine for 1 d prior to the administration of labeled ornithine, the total uptake of radioactivity into the root cells was not reduced, even though ornithine decarboxylase was specifically inactivated and the incorporation of the label to putrescine, N-methylputrescine, hyoscyamine and scopolamine markedly reduced. These and other results (Hashimoto et al., 1989, Planta 178, 123-130) are strong indications that tropane alkaloids in H. albus root cultures are synthesized from both ornithine and arginine by way of putrescine. PMID- 24212560 TI - First-line extracorporeal photochemotherapy for acute GVHD after unmanipulated haploidentical BMT following nonmyeloablative conditioning and post transplantation CY. PMID- 24212562 TI - Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells. AB - Single-unit umbilical cord blood (CB) SCT is limited by low total nucleated cell (TNC) dose. Co-infusion of CD34+ cells from a third party HLA-mismatched donor, known as dual or haplo-cord transplant, reduces the period of post-transplant neutropenia and related complications. The aim of this study was to analyze the value of early post-transplant peripheral blood (PB) and T cell chimerism after 28 dual transplants regarding CB engraftment. Cumulative incidence of myeloid engraftment at 30 days was 93% with a median time to engraftment of 14 days (10 29). Patients who developed CB graft failure (n=5) showed very low percentages of CB cells on days +14, +21 and +28 with decreasing dynamics. On the other hand, percentages of CB cells in patients who achieved CB engraftment increased over time. Interestingly, such patients showed two distinct chimerism dynamics in PB, but all of them showed a predominance of CB T cells early after SCT with increasing dynamics over time. Early post-transplant chimerism dynamics in PB and T cells predicts CB graft failure enabling rapid therapeutic measures to be applied. On the other hand, early increasing percentages of CB T cells correlates with ultimate CB engraftment. PMID- 24212563 TI - Fifteen-minute consultation: Bacillus Calmette-Guerin abscess and lymphadenitis. PMID- 24212561 TI - EBV-associated post-transplant lymphoproliferative disorder following in vivo T cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. AB - EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had ?10 000 and ?40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed. PMID- 24212564 TI - Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus. AB - Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh1 as a nutritional supplement in memory loss and neurodegenerative diseases. PMID- 24212565 TI - Involvement of TrkB- and p75(NTR)-signaling pathways in two contrasting forms of long-lasting synaptic plasticity. AB - The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75(NTR) pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75(NTR) pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75(NTR)-masking conditions, thus supporting the aforementioned hypothesis. PMID- 24212566 TI - US moves to ban trans fats. PMID- 24212567 TI - Characterization of Escherichia coli O157:H7 strains from contaminated raw beef trim during "high event periods". AB - The development and implementation of effective antimicrobial interventions by the beef processing industry in the United States have dramatically reduced the incidence of beef trim contamination by Escherichia coli O157:H7. However, individual processing plants still experience sporadic peaks in contamination rates where multiple E. coli O157:H7-positive lots are clustered in a short time frame. These peaks have been referred to as "high event periods" (HEP) of contamination. The results reported here detail the characterization of E. coli O157:H7 isolates from 21 HEP across multiple companies and processing plants to gain insight regarding the mechanisms causing these incidents. Strain genotypes were determined by pulsed-field gel electrophoresis, and isolates were investigated for characteristics linking them to human illness. Through these analyses, it was determined that individual HEP show little to no diversity in strain genotypes. Hence, each HEP has one strain type that makes up most, if not all, of the contamination. This is shown to differ from the genotypic diversity of E. coli O157:H7 found on the hides of cattle entering processing plants. In addition, it was found that a large proportion (81%) of HEP are caused by strain types associated with human illness. These results pose a potential challenge to the current model for finished product contamination during beef processing. PMID- 24212568 TI - Improved short-sequence-repeat genotyping of Mycobacterium avium subsp. paratuberculosis by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. AB - Accurate sequence analysis of mononucleotide repeat regions is difficult, complicating the use of short sequence repeats (SSRs) as a tool for bacterial strain discrimination. Although multiple SSR loci in the genome of Mycobacterium avium subsp. paratuberculosis allow genotyping of M. avium subsp. paratuberculosis isolates with high discriminatory power, further characterization of the most discriminatory loci is limited due to inherent difficulties in sequencing mononucleotide repeats. Here, a method was evaluated using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as an alternative to Sanger sequencing to further differentiate the dominant mycobacterial interspersed repetitive-unit (MIRU) variable-number tandem-repeat (VNTR) M. avium subsp. paratuberculosis type (n = 37) in Canadian dairy herds by targeting a highly discriminatory mononucleotide SSR locus. First, PCR-amplified DNA was digested with two restriction enzymes to yield a sufficiently small fragment containing the SSR locus. Second, MALDI-TOF MS was performed to identify the mass, and thus repeat length, of the target. Sufficiently intense, discriminating spectra were obtained to determine repeat lengths up to 15, an improvement over the limit of 11 using traditional sequencing techniques. Comparison to synthetic oligonucleotides and Sanger sequencing results confirmed a valid and reproducible assay that increased discrimination of the dominant M. avium subsp. paratuberculosis MIRU-VNTR type. Thus, MALDI-TOF MS was a reliable, fast, and automatable technique to accurately resolve M. avium subsp. paratuberculosis genotypes based on SSRs. PMID- 24212569 TI - Vibrio vulnificus bacteriophage SSP002 as a possible biocontrol agent. AB - A novel Vibrio vulnificus-infecting bacteriophage, SSP002, belonging to the Siphoviridae family, was isolated from the coastal area of the Yellow Sea of South Korea. Host range analysis revealed that the growth inhibition of phage SSP002 is relatively specific to V. vulnificus strains from both clinical and environmental samples. In addition, a one-step growth curve analysis and a bacteriophage stability test revealed a latent period of 65 min, a burst size of 23 +/- 2 PFU, as well as broad temperature (20 degrees C to 60 degrees C) and pH stability (pH 3 to 12) ranges. A Tn5 random transposon mutation of V. vulnificus and partial DNA sequencing of the inserted Tn5 regions revealed that the flhA, flhB, fliF, and fleQ mutants are resistant to SSP002 phage infection, suggesting that the flagellum may be the host receptor for infection. The subsequent construction of specific gene-inactivated mutants (flhA, flhB, fliF, and fleQ) and complementation experiments substantiated this. Previously, the genome of phage SSP002 was completely sequenced and analyzed. Comparative genomic analysis of phage SSP002 and Vibrio parahaemolyticus phage vB_VpaS_MAR10 showed differences among their tail-related genes, supporting different host ranges at the species level, even though their genome sequences are highly similar. An additional mouse survival test showed that the administration of phage SSP002 at a multiplicity of infection of 1,000 significantly protects mice from infection by V. vulnificus for up to 2 months, suggesting that this phage may be a good candidate for the development of biocontrol agents against V. vulnificus infection. PMID- 24212570 TI - Substrate promiscuity: AglB, the archaeal oligosaccharyltransferase, can process a variety of lipid-linked glycans. AB - Across evolution, N-glycosylation involves oligosaccharyltransferases that transfer lipid-linked glycans to selected Asn residues of target proteins. While these enzymes catalyze similar reactions in each domain, differences exist in terms of the chemical composition, length and degree of phosphorylation of the lipid glycan carrier, the sugar linking the glycan to the lipid carrier, and the composition and structure of the transferred glycan. To gain insight into how oligosaccharyltransferases cope with such substrate diversity, the present study analyzed the archaeal oligosaccharyltransferase AglB from four haloarchaeal species. Accordingly, it was shown that despite processing distinct lipid-linked glycans in their native hosts, AglB from Haloarcula marismortui, Halobacterium salinarum, and Haloferax mediterranei could readily replace their counterpart from Haloferax volcanii when introduced into Hfx. volcanii cells deleted of aglB. As the four enzymes show significant sequence and apparently structural homology, it appears that the functional similarity of the four AglB proteins reflects the relaxed substrate specificity of these enzymes. Such demonstration of AglB substrate promiscuity is important not only for better understanding of N glycosylation in Archaea and elsewhere but also for efforts aimed at transforming Hfx. volcanii into a glycoengineering platform. PMID- 24212572 TI - Biochemical and structural studies of NADH-dependent FabG used to increase the bacterial production of fatty acids under anaerobic conditions. AB - Major efforts in bioenergy research have focused on producing fuels that can directly replace petroleum-derived gasoline and diesel fuel through metabolic engineering of microbial fatty acid biosynthetic pathways. Typically, growth and pathway induction are conducted under aerobic conditions, but for operational efficiency in an industrial context, anaerobic culture conditions would be preferred to obviate the need to maintain specific dissolved oxygen concentrations and to maximize the proportion of reducing equivalents directed to biofuel biosynthesis rather than ATP production. A major concern with fermentative growth conditions is elevated NADH levels, which can adversely affect cell physiology. The purpose of this study was to identify homologs of Escherichia coli FabG, an essential reductase involved in fatty acid biosynthesis, that display a higher preference for NADH than for NADPH as a cofactor. Four potential NADH-dependent FabG variants were identified through bioinformatic analyses supported by crystallographic structure determination (1.3 to 2.0-A resolution). In vitro assays of cofactor (NADH/NADPH) preference in the four variants showed up to ~ 35-fold preference for NADH, which was observed with the Cupriavidus taiwanensis FabG variant. In addition, FabG homologs were overexpressed in fatty acid- and methyl ketone-overproducing E. coli host strains under anaerobic conditions, and the C. taiwanensis variant led to a 60% higher free fatty acid titer and 75% higher methyl ketone titer relative to the titers of the control strains. With further engineering, this work could serve as a starting point for establishing a microbial host strain for production of fatty acid-derived biofuels (e.g., methyl ketones) under anaerobic conditions. PMID- 24212571 TI - Harnessing genetic diversity in Saccharomyces cerevisiae for fermentation of xylose in hydrolysates of alkaline hydrogen peroxide-pretreated biomass. AB - The fermentation of lignocellulose-derived sugars, particularly xylose, into ethanol by the yeast Saccharomyces cerevisiae is known to be inhibited by compounds produced during feedstock pretreatment. We devised a strategy that combined chemical profiling of pretreated feedstocks, high-throughput phenotyping of genetically diverse S. cerevisiae strains isolated from a range of ecological niches, and directed engineering and evolution against identified inhibitors to produce strains with improved fermentation properties. We identified and quantified for the first time the major inhibitory compounds in alkaline hydrogen peroxide (AHP)-pretreated lignocellulosic hydrolysates, including Na(+), acetate, and p-coumaric (pCA) and ferulic (FA) acids. By phenotyping these yeast strains for their abilities to grow in the presence of these AHP inhibitors, one heterozygous diploid strain tolerant to all four inhibitors was selected, engineered for xylose metabolism, and then allowed to evolve on xylose with increasing amounts of pCA and FA. After only 149 generations, one evolved isolate, GLBRCY87, exhibited faster xylose uptake rates in both laboratory media and AHP switchgrass hydrolysate than its ancestral GLBRCY73 strain and completely converted 115 g/liter of total sugars in undetoxified AHP hydrolysate into more than 40 g/liter ethanol. Strikingly, genome sequencing revealed that during the evolution from GLBRCY73, the GLBRCY87 strain acquired the conversion of heterozygous to homozygous alleles in chromosome VII and amplification of chromosome XIV. Our approach highlights that simultaneous selection on xylose and pCA or FA with a wild S. cerevisiae strain containing inherent tolerance to AHP pretreatment inhibitors has potential for rapid evolution of robust properties in lignocellulosic biofuel production. PMID- 24212573 TI - Genes similar to the Vibrio parahaemolyticus virulence-related genes tdh, tlh, and vscC2 occur in other vibrionaceae species isolated from a pristine estuary. AB - Detection of the human pathogen Vibrio parahaemolyticus often relies on molecular biological analysis of species-specific virulence factor genes. These genes have been employed in determinations of V. parahaemolyticus population numbers and the prevalence of pathogenic V. parahaemolyticus strains. Strains of the Vibrionaceae species Photobacterium damselae, Vibrio diabolicus, Vibrio harveyi, and Vibrio natriegens, as well as strains similar to Vibrio tubiashii, were isolated from a pristine salt marsh estuary. These strains were examined for the V. parahaemolyticus hemolysin genes tdh, trh, and tlh and for the V. parahaemolyticus type III secretion system 2alpha gene vscC2 using established PCR primers and protocols. Virulence-related genes occurred at high frequencies in non-V. parahaemolyticus Vibrionaceae species. V. diabolicus was of particular interest, as several strains were recovered, and the large majority (>83%) contained virulence-related genes. It is clear that detection of these genes does not ensure correct identification of virulent V. parahaemolyticus. Further, the occurrence of V. parahaemolyticus-like virulence factors in other vibrios potentially complicates tracking of outbreaks of V. parahaemolyticus infections. PMID- 24212574 TI - Diversity in robustness of Lactococcus lactis strains during heat stress, oxidative stress, and spray drying stress. AB - In this study we tested 39 Lactococcus lactis strains isolated from diverse habitats for their robustness under heat and oxidative stress, demonstrating high diversity in survival (up to 4 log units). Strains with an L. lactis subsp. lactis phenotype generally displayed more-robust phenotypes than strains with an L. lactis subsp. cremoris phenotype, whereas the habitat from which the strains had been isolated did not appear to influence stress survival. Comparison of the stress survival phenotypes with already available comparative genomic data sets revealed that the absence or presence of specific genes, including genes encoding a GntR family transcriptional regulator, a manganese ABC transporter permease, a cellobiose phosphotransferase system (PTS) component, the FtsY protein, and hypothetical proteins, was associated with heat or oxidative stress survival. Finally, 14 selected strains also displayed diversity in survival after spray drying, ranging from 20% survival for the most robust strains, which appears acceptable for industrial application, to 0.1% survival for the least-tolerant strains. The high and low levels of survival upon spray drying correlated clearly with the combined robustness under heat and oxidative stress. These results demonstrate the relevance of screening culture collections for robustness under heat and oxidative stress on top of the typical screening for acidifying and flavor-forming properties. PMID- 24212575 TI - Phenotypic effect of "Candidatus Rickettsiella viridis," a facultative symbiont of the pea aphid (Acyrthosiphon pisum), and its interaction with a coexisting symbiont. AB - A gammaproteobacterial facultative symbiont of the genus Rickettsiella was recently identified in the pea aphid, Acyrthosiphon pisum. Infection with this symbiont altered the color of the aphid body from red to green, potentially affecting the host's ecological characteristics, such as attractiveness to different natural enemies. In European populations of A. pisum, the majority of Rickettsiella-infected aphids also harbor another facultative symbiont, of the genus Hamiltonella. We investigated this Rickettsiella symbiont for its interactions with the coinfecting Hamiltonella symbiont, its phenotypic effects on A. pisum with and without Hamiltonella coinfection, and its infection prevalence in A. pisum populations. Histological analyses revealed that coinfecting Rickettsiella and Hamiltonella exhibited overlapping localizations in secondary bacteriocytes, sheath cells, and hemolymph, while Rickettsiella specific localization was found in oenocytes. Rickettsiella infections consistently altered hosts' body color from red to green, where the greenish hue was affected by both host and symbiont genotypes. Rickettsiella-Hamiltonella coinfections also changed red aphids to green; this greenish hue tended to be enhanced by Hamiltonella coinfection. With different host genotypes, Rickettsiella infection exhibited either weakly beneficial or nearly neutral effects on host fitness, whereas Hamiltonella infection and Rickettsiella Hamiltonella coinfection had negative effects. Despite considerable frequencies of Rickettsiella infection in European and North American A. pisum populations, no Rickettsiella infection was detected among 1,093 insects collected from 14 sites in Japan. On the basis of these results, we discuss possible mechanisms for the interaction of Rickettsiella with other facultative symbionts, their effects on their hosts' phenotypes, and their persistence in natural host populations. We propose the designation "Candidatus Rickettsiella viridis" for the symbiont. PMID- 24212577 TI - PhaM is the physiological activator of poly(3-hydroxybutyrate) (PHB) synthase (PhaC1) in Ralstonia eutropha. AB - Poly(3-hydroxybutyrate) (PHB) synthase (PhaC1) is the key enzyme of PHB synthesis in Ralstonia eutropha and other PHB-accumulating bacteria and catalyzes the polymerization of 3-hydroxybutyryl-CoA to PHB. Activity assays of R. eutropha PHB synthase are characterized by the presence of lag phases and by low specific activity. It is assumed that the lag phase is caused by the time necessary to convert the inactive PhaC1 monomer into the active dimeric form by an unknown priming process. The lag phase can be reduced by addition of nonionic detergents such as hecameg [6-O-(N-heptyl-carbamoyl)-methyl-alpha-D-glucopyranoside], which apparently accelerates the formation of PhaC1 dimers. We identified the PHB granule-associated protein (PGAP) PhaM as the natural primer (activator) of PHB synthase activity. PhaM was recently discovered as a novel type of PGAP with multiple functions in PHB metabolism. Addition of PhaM to PHB synthase assays resulted in immediate polymerization of 3HB coenzyme A with high specific activity and without a significant lag phase. The effect of PhaM on (i) PhaC1 activity, (ii) oligomerization of PhaC1, (iii) complex formation with PhaC1, and (iv) PHB granule formation in vitro and in vivo was shown by cross-linking experiments of purified proteins (PhaM, PhaC1) with glutardialdehyde, by size exclusion chromatography, and by fluorescence microscopic detection of de novo synthesized PHB granules. PMID- 24212578 TI - Metaproteomics analysis reveals the adaptation process for the chicken gut microbiota. AB - The animal gastrointestinal tract houses a large microbial community, the gut microbiota, that confers many benefits to its host, such as protection from pathogens and provision of essential metabolites. Metagenomic approaches have defined the chicken fecal microbiota in other studies, but here, we wished to assess the correlation between the metagenome and the bacterial proteome in order to better understand the healthy chicken gut microbiota. Here, we performed high throughput sequencing of 16S rRNA gene amplicons and metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. 16 rRNA gene sequencing analysis identified Clostridiales, Bacteroidaceae, and Lactobacillaceae species as the most abundant species in the gut. For metaproteomics analysis, peptides were generated by using the Fasp method and subsequently fractionated by strong anion exchanges. Metaproteomics analysis identified 3,673 proteins. Among the most frequently identified proteins, 380 proteins belonged to Lactobacillus spp., 155 belonged to Clostridium spp., and 66 belonged to Streptococcus spp. The most frequently identified proteins were heat shock chaperones, including 349 GroEL proteins, from many bacterial species, whereas the most abundant enzymes were pyruvate kinases, as judged by the number of peptides identified per protein (spectral counting). Gene ontology and KEGG pathway analyses revealed the functions and locations of the identified proteins. The findings of both metaproteomics and 16S rRNA sequencing analyses are discussed. PMID- 24212579 TI - A vector library for silencing central carbon metabolism genes with antisense RNAs in Escherichia coli. AB - We describe here the construction of a series of 71 vectors to silence central carbon metabolism genes in Escherichia coli. The vectors inducibly express antisense RNAs called paired-terminus antisense RNAs, which have a higher silencing efficacy than ordinary antisense RNAs. By measuring mRNA amounts, measuring activities of target proteins, or observing specific phenotypes, it was confirmed that all the vectors were able to silence the expression of target genes efficiently. Using this vector set, each of the central carbon metabolism genes was silenced individually, and the accumulation of metabolites was investigated. We were able to obtain accurate information on ways to increase the production of pyruvate, an industrially valuable compound, from the silencing results. Furthermore, the experimental results of pyruvate accumulation were compared to in silico predictions, and both sets of results were consistent. Compared to the gene disruption approach, the silencing approach has an advantage in that any E. coli strain can be used and multiple gene silencing is easily possible in any combination. PMID- 24212576 TI - Newly cultured bacteria with broad diversity isolated from eight-week continuous culture enrichments of cow feces on complex polysaccharides. AB - One of the functions of the mammalian large intestinal microbiota is the fermentation of plant cell wall components. In ruminant animals, the majority of their nutrients are obtained via pregastric fermentation; however, up to 20% can be recovered from microbial fermentation in the large intestine. Eight-week continuous culture enrichments of cattle feces with cellulose and xylan-pectin were used to isolate bacteria from this community. A total of 459 bacterial isolates were classified phylogenetically using 16S rRNA gene sequencing. Six phyla were represented: Firmicutes (51.9%), Bacteroidetes (30.9%), Proteobacteria (11.1%), Actinobacteria (3.5%), Synergistetes (1.5%), and Fusobacteria (1.1%). The majority of bacterial isolates had <98.5% identity to cultured bacteria with sequences in the Ribosomal Database Project and thus represent new species and/or genera. Within the Firmicutes isolates, most were classified in the families Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Clostridiaceae I. The majority of the Bacteroidetes were most closely related to Bacteroides thetaiotaomicron, B. ovatus, and B. xylanisolvens and members of the Porphyromonadaceae family. Many of the Firmicutes and Bacteroidetes isolates were related to species demonstrated to possess enzymes which ferment plant cell wall components; the others were hypothesized to cross-feed these bacteria. The microbial communities that arose in these enrichment cultures had broad bacterial diversity. With over 98% of the isolates not represented as previously cultured, there are new opportunities to study the genomic and metabolic capacities of these members of the complex intestinal microbiota. PMID- 24212581 TI - In silico rational design and systems engineering of disulfide bridges in the catalytic domain of an alkaline alpha-amylase from Alkalimonas amylolytica to improve thermostability. AB - High thermostability is required for alkaline alpha-amylases to maintain high catalytic activity under the harsh conditions used in textile production. In this study, we attempted to improve the thermostability of an alkaline alpha-amylase from Alkalimonas amylolytica through in silico rational design and systems engineering of disulfide bridges in the catalytic domain. Specifically, 7 residue pairs (P35-G426, Q107-G167, G116-Q120, A147-W160, G233-V265, A332-G370, and R436 M480) were chosen as engineering targets for disulfide bridge formation, and the respective residues were replaced with cysteines. Three single disulfide bridge mutants-P35C-G426C, G116C-Q120C, and R436C-M480C-of the 7 showed significantly enhanced thermostability. Combinational mutations were subsequently assessed, and the triple mutant P35C-G426C/G116C-Q120C/R436C-M480C showed a 6-fold increase in half-life at 60 degrees C and a 5.2 degrees C increase in melting temperature compared with the wild-type enzyme. Interestingly, other biochemical properties of this mutant also improved: the optimum temperature increased from 50 degrees C to 55 degrees C, the optimum pH shifted from 9.5 to 10.0, the stable pH range extended from 7.0 to 11.0 to 6.0 to 12.0, and the catalytic efficiency (kcat/Km) increased from 1.8 * 10(4) to 2.4 * 10(4) liters/g . min. The possible mechanism responsible for these improvements was explored through comparative analysis of the model structures of wild-type and mutant enzymes. The disulfide bridge engineering strategy used in this work may be applied to improve the thermostability of other industrial enzymes. PMID- 24212582 TI - Nanoscale cell wall deformation impacts long-range bacterial adhesion forces on surfaces. AB - Adhesion of bacteria occurs on virtually all natural and synthetic surfaces and is crucial for their survival. Once they are adhering, bacteria start growing and form a biofilm, in which they are protected against environmental attacks. Bacterial adhesion to surfaces is mediated by a combination of different short- and long-range forces. Here we present a new atomic force microscopy (AFM)-based method to derive long-range bacterial adhesion forces from the dependence of bacterial adhesion forces on the loading force, as applied during the use of AFM. The long-range adhesion forces of wild-type Staphylococcus aureus parent strains (0.5 and 0.8 nN) amounted to only one-third of these forces measured for their more deformable isogenic Deltapbp4 mutants that were deficient in peptidoglycan cross-linking. The measured long-range Lifshitz-Van der Waals adhesion forces matched those calculated from published Hamaker constants, provided that a 40% ellipsoidal deformation of the bacterial cell wall was assumed for the Deltapbp4 mutants. Direct imaging of adhering staphylococci using the AFM peak force quantitative nanomechanical property mapping imaging mode confirmed a height reduction due to deformation in the Deltapbp4 mutants of 100 to 200 nm. Across naturally occurring bacterial strains, long-range forces do not vary to the extent observed here for the Deltapbp4 mutants. Importantly, however, extrapolating from the results of this study, it can be concluded that long-range bacterial adhesion forces are determined not only by the composition and structure of the bacterial cell surface but also by a hitherto neglected, small deformation of the bacterial cell wall, facilitating an increase in contact area and, therewith, in adhesion force. PMID- 24212583 TI - Use of Bacteroidales microbial source tracking to monitor fecal contamination in fresh produce production. AB - In recent decades, fresh and minimally processed produce items have been associated with an increasing proportion of food-borne illnesses. Most pathogens associated with fresh produce are enteric (fecal) in origin, and contamination can occur anywhere along the farm-to-fork chain. Microbial source tracking (MST) is a tool developed in the environmental microbiology field to identify and quantify the dominant source(s) of fecal contamination. This study investigated the utility of an MST method based on Bacteroidales 16S rRNA gene sequences as a means of identifying potential fecal contamination, and its source, in the fresh produce production environment. The method was applied to rinses of fresh produce, source and irrigation waters, and harvester hand rinses collected over the course of 1 year from nine farms (growing tomatoes, jalapeno peppers, and cantaloupe) in Northern Mexico. Of 174 samples, 39% were positive for a universal Bacteroidales marker (AllBac), including 66% of samples from cantaloupe farms (3.6 log10 genome equivalence copies [GEC]/100 ml), 31% of samples from tomato farms (1.7 log10 GEC/100 ml), and 18% of samples from jalapeno farms (1.5 log10 GEC/100 ml). Of 68 AllBac-positive samples, 46% were positive for one of three human-specific markers, and none were positive for a bovine-specific marker. There was no statistically significant correlation between Bacteroidales and generic Escherichia coli across all samples. This study provides evidence that Bacteroidales markers may serve as alternative indicators for fecal contamination in fresh produce production, allowing for determination of both general contamination and that derived from the human host. PMID- 24212584 TI - Polycyclic aromatic hydrocarbon degradation of phytoplankton-associated Arenibacter spp. and description of Arenibacter algicola sp. nov., an aromatic hydrocarbon-degrading bacterium. AB - Pyrosequencing of the bacterial community associated with a cosmopolitan marine diatom during enrichment with crude oil revealed several Arenibacter phylotypes, of which one (OTU-202) had become significantly enriched by the oil. Since members of the genus Arenibacter have not been previously shown to degrade hydrocarbons, we attempted to isolate a representative strain of this genus in order to directly investigate its hydrocarbon-degrading potential. Based on 16S rRNA sequencing, one isolate (designated strain TG409(T)) exhibited >99% sequence identity to three type strains of this genus. On the basis of phenotypic and genotypic characteristics, strain TG409(T) represents a novel species in the genus Arenibacter, for which the name Arenibacter algicola sp. nov. is proposed. We reveal for the first time that polycyclic aromatic hydrocarbon (PAH) degradation is a shared phenotype among members of this genus, indicating that it could be used as a taxonomic marker for this genus. Kinetic data for PAH mineralization rates showed that naphthalene was preferred to phenanthrene, and its mineralization was significantly enhanced in the presence of glass wool (a surrogate for diatom cell surfaces). During enrichment on hydrocarbons, strain TG409(T) emulsified n-tetradecane and crude oil, and cells were found to be preferentially attached to oil droplets, indicating an ability by the strain to express cell surface amphiphilic substances (biosurfactants or bioemulsifiers) as a possible strategy to increase the bioavailability of hydrocarbons. This work adds to our growing knowledge on the diversity of bacterial genera in the ocean contributing to the degradation of oil contaminants and of hydrocarbon-degrading bacteria found living in association with marine eukaryotic phytoplankton. PMID- 24212585 TI - Polysulfides as intermediates in the oxidation of sulfide to sulfate by Beggiatoa spp. AB - Zero-valent sulfur is a key intermediate in the microbial oxidation of sulfide to sulfate. Many sulfide-oxidizing bacteria produce and store large amounts of sulfur intra- or extracellularly. It is still not understood how the stored sulfur is metabolized, as the most stable form of S(0) under standard biological conditions, orthorhombic alpha-sulfur, is most likely inaccessible to bacterial enzymes. Here we analyzed the speciation of sulfur in single cells of living sulfide-oxidizing bacteria via Raman spectroscopy. Our results showed that under various ecological and physiological conditions, all three investigated Beggiatoa strains stored sulfur as a combination of cyclooctasulfur (S8) and inorganic polysulfides (Sn(2-)). Linear sulfur chains were detected during both the oxidation and reduction of stored sulfur, suggesting that Sn(2-) species represent a universal pool of bioavailable sulfur. Formation of polysulfides due to the cleavage of sulfur rings could occur biologically by thiol-containing enzymes or chemically by the strong nucleophile HS(-) as Beggiatoa migrates vertically between oxic and sulfidic zones in the environment. Most Beggiatoa spp. thus far studied can oxidize sulfur further to sulfate. Our results suggest that the ratio of produced sulfur and sulfate varies depending on the sulfide flux. Almost all of the sulfide was oxidized directly to sulfate under low sulfide-flux conditions, whereas only 50% was oxidized to sulfate under high sulfide-flux conditions leading to S(0) deposition. With Raman spectroscopy we could show that sulfate accumulated in Beggiatoa filaments, reaching intracellular concentrations of 0.72 to 1.73 M. PMID- 24212586 TI - Type IV pilus biogenesis, twitching motility, and DNA uptake in Thermus thermophilus: discrete roles of antagonistic ATPases PilF, PilT1, and PilT2. AB - Natural transformation has a large impact on lateral gene flow and has contributed significantly to the ecological diversification and adaptation of bacterial species. Thermus thermophilus HB27 has emerged as the leading model organism for studies of DNA transporters in thermophilic bacteria. Recently, we identified a zinc-binding polymerization nucleoside triphosphatase (NTPase), PilF, which is essential for the transport of DNA through the outer membrane. Here, we present genetic evidence that PilF is also essential for the biogenesis of pili. One of the most challenging questions was whether T. thermophilus has any depolymerization NTPase acting as a counterplayer of PilF. We identified two depolymerization NTPases, PilT1 (TTC1621) and PilT2 (TTC1415), both of which are required for type IV pilus (T4P)-mediated twitching motility and adhesion but dispensable for natural transformation. This suggests that T4P dynamics are not required for natural transformation. The latter finding is consistent with our suggestion that in T. thermophilus, T4P and natural transformation are linked but distinct systems. PMID- 24212588 TI - [CNS-mediated disintegration of homeostasis by chronic stress]. PMID- 24212580 TI - Rumen methanogenic genotypes differ in abundance according to host residual feed intake phenotype and diet type. AB - Methane is an undesirable end product of rumen fermentative activity because of associated environmental impacts and reduced host feed efficiency. Our study characterized the rumen microbial methanogenic community in beef cattle divergently selected for phenotypic residual feed intake (RFI) while offered a high-forage (HF) diet followed by a low-forage (LF) diet. Rumen fluid was collected from 14 high-RFI (HRFI) and 14 low-RFI (LRFI) animals at the end of both dietary periods. 16S rRNA gene clone libraries were used, and methanogen specific tag-encoded pyrosequencing was carried out on the samples. We found that Methanobrevibacter spp. are the dominant methanogens in the rumen, with Methanobrevibacter smithii being the most abundant species. Differences in the abundance of Methanobrevibacter smithii and Methanosphaera stadtmanae genotypes were detected in the rumen of animals offered the LF compared to the HF diet while the abundance of Methanobrevibacter smithii genotypes was different between HRFI and LRFI animals irrespective of diet. Our results demonstrate that while a core group of methanogen operational taxonomic units (OTUs) exist across diet and phenotype, significant differences were observed in the distribution of genotypes within those OTUs. These changes in genotype abundance may contribute to the observed differences in methane emissions between efficient and inefficient animals. PMID- 24212587 TI - Efficient isolation of ion beam-induced mutants for homoeologous loci in common wheat and comparison of the contributions of Glu-1 loci to gluten functionality. AB - KEY MESSAGE: Ion beam mutations can be efficiently isolated and deployed for functional comparison of homoeologous loci in polyploid plants, and Glu - 1 loci differ substantially in their contribution to wheat gluten functionality. To efficiently conduct genetic analysis, it is beneficial to have multiple types of mutants for the genes under investigation. Here, we demonstrate that ion beam induced deletion mutants can be efficiently isolated for comparing the function of homoeologous loci of common wheat (Triticum aestivum). Through fragment analysis of PCR products from M2 plants, ion beam mutants lacking homoeologous Glu-A1, Glu-B1 or Glu-D1 loci, which encode high molecular weight glutenin subunits (HMW-GSs) and affect gluten functionality and end-use quality of common wheat, could be isolated simultaneously. Three deletion lines missing Glu-A1, Glu B1 or Glu-D1 were developed from the original mutants, with the Glu-1 genomic regions deleted in these lines estimated using newly developed DNA markers. Apart from lacking the target HMW-GSs, the three lines all showed decreased accumulation of low molecular weight glutenin subunits (LMW-GSs) and increased amounts of gliadins. Based on the test data of five gluten and glutenin macropolymer (GMP) parameters obtained with grain samples harvested from two environments, we conclude that the genetic effects of Glu-1 loci on gluten functionality can be ranked as Glu-D1 > Glu-B1 > Glu-A1. Furthermore, it is suggested that Glu-1 loci contribute to gluten functionality both directly (by promoting the formation of GMP) and indirectly (through keeping the balance among HMW-GSs, LMW-GSs and gliadins). Finally, the efficient isolation of ion beam mutations for functional comparison of homoeologous loci in polyploid plants and the usefulness of Glu-1 deletion lines for further studying the contribution of Glu-1 loci to gluten functionality are discussed. PMID- 24212589 TI - [Involvement of spinally-infiltrated immune cells in peripheral nerve injury induced neuropathic pain: roles of TRPM2]. PMID- 24212590 TI - [Neurodevelopmental impairment following neonatal immune challenge in mice]. PMID- 24212591 TI - [Ca(2+) imaging of neurons and astrocytes with genetically encoded Ca(2+) indicators]. PMID- 24212592 TI - [Microglia and synaptic reorganization: focus on the movement and functions of microglial processes]. PMID- 24212593 TI - [Quantitative analysis of phosphoinositides and inositol polyphosphates using an HPLC system]. PMID- 24212594 TI - [Drug Discovery and Medical Technology Program in RIKEN life science innovation]. PMID- 24212595 TI - [Pharmacological properties and clinical efficacy of apixaban (Eliquis((r))]. PMID- 24212596 TI - [Substance P in antitumor drug-induced adverse reactions]. PMID- 24212597 TI - Cocaine-induced agitated delirium: a case report and review. AB - Cocaine use continues to be a major public health problem in the United States. Although many of the initial signs and symptoms of cocaine intoxication result from increased stimulation of the sympathetic nervous system, this condition can present as a spectrum of acuity from hypertension and tachycardia to multiorgan system failure. Classic features of acute intoxication include tachycardia, arterial vasoconstriction, enhanced thrombus formation, mydriasis, psychomotor agitation, and altered level of consciousness. At the extreme end of this toxidrome is a rare condition known as cocaine-induced agitated delirium. This syndrome is characterized by severe cardiopulmonary dysfunction, hyperthermia, and acute neurologic changes frequently leading to death. We report a case of cocaine-induced agitated delirium in a man who presented to our institution in a paradoxical form of circulatory shock. Rapid evaluation, recognition, and proper management enabled our patient not only to survive but also to leave the hospital without neurologic sequelae. PMID- 24212598 TI - Making a Difference in Eye Care of the Critically Ill Patients. AB - Ocular surface disorders are frequently encountered in patients under sedation and paralyzed patients in intensive care units (ICUs). In the ICUs, treatment is usually focused on the management of organ failures, and eye care becomes a side issue. As a result, ophthalmological complications do occur (incidence ranges from 3.6% to 60%) and are frequently overlooked in this setting. To identify the best available evidence in providing the best eye care to prevent exposure keratopathy, a literature review was performed. The databases of PUBMED, COCHRAN, and EMBASE library were searched. We only looked at higher quality articles. Among various eye care measures that have been advocated to prevent exposure keratopathy, the most effective is the application of polyethylene covers. Early diagnosis and effective treatment will help prevent microbial keratitis and visual loss. PMID- 24212599 TI - Mature trauma intensivist model improves intensive care unit efficiency but not mortality. AB - BACKGROUND: Although the Leap Frog intensivist staffing model has been shown to improve outcomes in the intensive care unit (ICU), to date, no one has examined the effect of an intensivist model in a dedicated trauma ICU. With stricter adherence to evidence-based protocols and 24-hour availability, we hypothesized that a mature intensivist model in a trauma ICU would decrease mortality. METHODS: Level II trauma center trauma ICU admissions 2006 to 2011. The ICU care provided by 6 trauma intensivists. Two periods were compared: early (2006-2008) and mature (2009-2011). Patients matched on age, Injury Severity Score (ISS), preexisting conditions, and so on in a univariate analysis, with significant variables placed in a logistic regression model, with mortality as the outcome. RESULTS: A total of 3527 patients (2999 excluding do not resuscitate status) were reviewed. Age >=65 (odds ratio [OR] 2.38, P < .001), ISS >=17 (OR 3.3, P < .001), coagulopathy (OR 1.64, P = .004), and anemia (OR 1.73, P = .02) were independent predictors of mortality. Multivariate logistic model encompassing these factors found no statistically significant differences in mortality across the 6-year period. The ICU efficiency showed significant improvements in terms of ventilator days (30.1% EARLY vs 24.4% MATURE; P < .001), decreases in mean consultant use per patient (0.55 +/- 0.85 EARLY vs 0.40 +/- 0.74 MATURE; P < .001), and increase in number of bedside procedures per patient (0.09 +/- 0.48 EARLY vs 0.40 +/- 0.74 MATURE; P < .001 CONCLUSIONS: Our mature intensivists staffing model shows improvement in ICU throughput (ventilator days, ICU days, decreased consultant use, and increased bedside procedures) but no survival benefit. Further improvements in overall trauma mortality may lie in the resuscitative and operative phase of patient care. PMID- 24212600 TI - Neurogenic Stunned Myocardium Following Acute Subarachnoid Hemorrhage: Pathophysiology and Practical Considerations. AB - Neurogenic stunned myocardium (NSM) is a triad of transient left ventricular dysfunction, electrocardiogram changes, and elevation in cardiac enzymes, often mimicking a myocardial infarction. It has been described following acute brain injury. The purported mechanism is catecholamine excess resulting in cardiac dysfunction. From the clinical standpoint, the most frequently encountered electrocardiographic changes are QTc prolongation and ST-T changes, with modest elevations in troponin levels. Basal and mid-ventricular segments of the left ventricle are most commonly involved. NSM poses therapeutic challenges when it occurs secondary to aneurysmal subarachnoid hemorrhage, particularly in the setting of coexisting vasospasm. Overall, NSM carries good prognosis if recognized early, with appropriate management of hemodynamic and cardiopulmonary parameters. PMID- 24212601 TI - 3R and 4R tau isoforms in paired helical filaments in Alzheimer's disease. PMID- 24212602 TI - Histologically defined central nervous system primitive neuro-ectodermal tumours (CNS-PNETs) display heterogeneous DNA methylation profiles and show relationships to other paediatric brain tumour types. PMID- 24212603 TI - The role of apoptosis in the pathology of pancreatic cancer. AB - Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer. PMID- 24212604 TI - Clinically relevant anticancer polymer Paclitaxel therapeutics. AB - The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic. PMID- 24212605 TI - Pain management in pancreatic cancer. AB - A majority of pancreatic cancer patients present with pain at the time of diagnosis. Pain management can be challenging in light of the aggressive nature of this cancer. Apart from conventional pharmacotherapy, timely treatment with neurolytic celiac plexus block (NCPB) has been shown to be of benefit. NCPB has demonstrated efficacious pain control in high quality studies with analgesic effects lasting one to two months. NCPB has also shown to decrease the requirements of narcotics, and thus decrease opioid related side effects. Another option for the control of moderate to severe pain is intrathecal therapy (IT). Delivery of analgesic medications intrathecally allows for lower dosages of medications and thus reduced toxicity. Both of the above mentioned interventional procedures have been shown to have low complication rates, and be safe and effective. Ultimately, comprehensive pancreatic cancer pain management necessitates understanding of pain mechanisms and delivery of sequential validated therapeutic interventions within a multidisciplinary patient care model. PMID- 24212606 TI - Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer. AB - The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(epsilon caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX loaded micelles as compared to multiple administrations of free DOX. PMID- 24212607 TI - Screening technologies for target identification in pancreatic cancer. AB - Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments. PMID- 24212608 TI - Detection of up to 65% of Precancerous Lesions of the Human Colon and Rectum by Mutation Analysis of APC, K-Ras, B-Raf and CTNNB1. AB - In the present study a recently conceived 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signaling pathways was used to analyze 20 colorectal serrated lesions and 41 colorectal adenoma samples and to determine the percentage of each of the above-mentioned potentially precancerous lesions carrying at least one of the four above-mentioned genes in a mutated form. CTNNB1 and B-Raf were screened by PCR-single-strand conformation polymorphism analysis, K-Ras by restriction fragment length polymorphism analysis and the APC gene mutation cluster region (codons 1243-1567) by direct DNA sequencing. APC mutations were only detected in 10% of the serrated lesions but in 34% of the adenomas. Twenty percent of the serrated lesions and 14% of the adenomas carried a mutated K-Ras. B-Raf was found to be mutated in 50% of the serrated lesions and in 22% of the adenomas. CTNNB1 was altered in 12% of the adenomas, but not in serrated lesions. By using the above gene marker panel it could be shown that 65% of the serrated lesions and 61% of the adenomas carried at least one of the four genes in a mutated form. Based on its excellent performance in detecting mutations in sporadic preneoplastic (in this study) and neoplastic lesions (in a previous study) of the human colon and rectum, this primer combination might also be suited to efficiently and non-invasively detect genetic alterations in stool DNA of patients with early colorectal cancer. PMID- 24212609 TI - Membrane drug transporters and chemoresistance in human pancreatic carcinoma. AB - Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5 overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil. PMID- 24212611 TI - Assessment of Serosal Invasion and Criteria for the Classification of Pathological (p) T4 Staging in Colorectal Carcinoma: Confusions, Controversies and Criticisms. AB - Transmural spread by colorectal carcinoma can result in tumor invasion of the serosal surface and, hence, more likely dissemination within the peritoneal cavity and potentially to additional metastatic sites. The adverse prognostic significance of serosal invasion is widely accepted and its presence may be considered an indication for chemotherapy in patients with node negative disease. However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases. Therefore, serosal invasion may be under-diagnosed in a significant proportion of tumors, potentially leading to sub-optimal treatment of high-risk patients. The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely. The relative prognostic significance of serosal invasion and of direct tumor spread to other organs, both of which are incorporated within the pT4 category of the AJCC/UICC TNM staging system, remains unclear. Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate. PMID- 24212612 TI - Dependence of Relative Expression of NTR1 and EGFR on Cell Density and Extracellular pH in Human Pancreatic Cancer Cell Lines. AB - Pancreatic adenocarcinoma is a devastating disease characterized by early dissemination and poor prognosis. These solid tumors express receptors for neuropeptides like neurotensin (NT) or epidermal growth factor (EGF) and exhibit acidic regions when grown beyond a certain size. We previously demonstrated increases in intracellular Ca2+ levels, intracellular pH and interleukin-8 (IL-8) secretion in BxPC-3 and PANC-1 pancreatic cancer cells in response to a stable NT analog. The present study aimed at investigation of the dependence of the relative expression of NT receptor 1 (NTR1) and EGFR in BxPC-3 and MIA PaCa-2 cells on cell density and extracellular pH (pHe). MTT assays revealed the NTR1 inhibitor SR 142948-sensitive Lys8-psi-Lys9NT (8-13)-induced proliferation in BxPC-3 and PANC-1 cells. Confluent cultures of BxPC3 and HT-29 lines exhibited highest expression of NTR1 and lowest of EGFR and expression of NTR1 was maximal at slightly acidic pHe. IL-8 production was stimulated by Lys8-psi-Lys9NT (8-13) and even enhanced at both acidic and alkaline pHe in BxPC-3 and PANC-1 cells. In conclusion, our in vitro study suggests that one contributing factor to the minor responses obtained with EGFR-directed therapy may be downregulation of this receptor in tumor cell aggregates, possibly resulting in acquisition of a more aggressive phenotype via other growth factor receptors like NTR1. PMID- 24212613 TI - Nuclear receptor small heterodimer partner in apoptosis signaling and liver cancer. AB - Small heterodimer partner (SHP, NR0B2) is a unique orphan nuclear receptor that contains the dimerization and a putative ligand-binding domain, but lacks the conserved DNA binding domain. SHP exerts its physiological function as an inhibitor of gene transcription through physical interaction with multiple nuclear receptors and transcriptional factors. SHP is a critical transcriptional regulator affecting diverse biological functions, including bile acid, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology. Recently, we and others have demonstrated that SHP is an epigenetically regulated transcriptional repressor that suppresses the development of liver cancer. In this review, we summarize recent major findings regarding the role of SHP in cell proliferation, apoptosis, and DNA methylation, and discuss recent progress in understanding the function of SHP as a tumor suppressor in the development of liver cancer. Future study will be focused on identifying SHP associated novel pro-oncogenes and anti-oncogenes in liver cancer progression and applying the knowledge gained on SHP in liver cancer prevention, diagnosis and treatment. PMID- 24212610 TI - Decoding melanoma metastasis. AB - Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis. PMID- 24212615 TI - Anti-Neuroblastoma Activity of Gold Nanorods Bound with GD2 Monoclonal Antibody under Near-Infrared Laser Irradiation. AB - High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. To achieve tumor-selective delivery, disialoganglioside (GD2) expressed by almost all neuroblastoma tumors represents a potential molecular target that can be exploited for tumor-selective delivery. In this study, GD2 monoclonal antibody (anti-GD2) was conjugated to gold nanorods (GNRs) which are one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser light and convert it to energy for photothermolysis of tumor cells. Thiolated chitosan, due to its biocompatibility, was used to replace cetyltrimethylammonium bromide (CTAB) originally used in the synthesis of gold nanorods. In order to specifically target GD2 overexpressed on the surface of neuroblastoma stNB-V1 cells, anti-GD2 was conjugated to chitosan modified GNRs (CGNRs). To examine the fate of CGNRs conjugated with anti-GD2 after incubation with neuroblastoma cells, rhadoamine B was labeled on CGNRs functionalized with anti-GD2. Our results illustrated that anti-GD2-conjugated CGNRs were extensively endocytosed by GD2+ stNB-V1 neuroblastoma cells via antibody-mediated endocytosis. In addition, we showed that anti-GD2 bound CGNRs were not internalized by GD2- SH-SY5Y neuroblastoma cells. After anti-GD2-linked CGNRs were incubated with neuroblatoma cells for six hours, the treated cells were further irradiated with 808 nm NIR laser. Post-NIR laser exposure, when examined by calcein-AM dye, stNB-V1 cells all underwent necrosis, while non-GD2 expressing SH-SY5Y cells all remained viable. Based on the in vitro study, CGNRs bound with anti-GD2 has the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure. PMID- 24212614 TI - Vitamin d and pancreatic cancer-an update. AB - The non-classical actions of vitamin D, namely anti-proliferation, pro differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers. The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer. Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss briefly the origin and current therapy of pancreatic cancer, the history, source, metabolism and functions of vitamin D, the recent progress in the epidemiological studies of sunlight, and vitamin D status, and biochemical studies of vitamin D analogs in the prevention and treatment of pancreatic cancer. PMID- 24212616 TI - Targeting apoptosis signaling in pancreatic cancer. AB - The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery. PMID- 24212617 TI - Rational and irrational issues in breast cancer screening. AB - Evidence on the efficacy of breast screening from randomized controlled trials conducted in the last decades of the 1900s is reviewed. For decades, controversy about their results has centered on the magnitude of benefit in terms of breast cancer mortality reduction that can be achieved. However more recently, several expert bodies have estimated the benefits to be smaller than initially expected and concerns have been raised about screening consequences such as over-diagnosis and unnecessary treatment. Trials with substantial mortality reduction have been lauded and others with null effects have been critiqued. Critiques of the Canadian National Breast Screening Study are refuted. Extreme responses by screening advocates to the United States Preventive Services Task Force 2009 guidelines are described. The role vested interests play in determining health policy is clearly revealed in the response to the guidelines and should be more generally known. A general reluctance to explore unexpected results or to accept new paradigms is briefly discussed. PMID- 24212618 TI - The Hemostasis Apparatus in Pancreatic Cancer and Its Importance beyond Thrombosis. AB - Laboratory evidence of aberrant coagulation is found in the majority of patients with advanced pancreatic cancer and a clinical consequence of this is the high incidence and prevalence of vascular thromboembolic events. Other sequelae are hypothesized to be the facilitation and acceleration of mechanisms that define the malignant phenotype, such as invasion, trafficking and anchoring, establishing the metastatic niche and inducing angiogenesis. We review the in vitro and preclinical evidence that supports the role of the coagulation apparatus in the metastatic process of pancreatic cancer, with a particular emphasis on interaction of this pathway with clinically-targeted growth factor receptor pathways. Links between hemostasis, angiogenesis and epidermal growth factor pathways and their significance as therapeutic targets are considered. PMID- 24212619 TI - Why victory in the war on cancer remains elusive: biomedical hypotheses and mathematical models. AB - We discuss philosophical, methodological, and biomedical grounds for the traditional paradigm of cancer and some of its critical flaws. We also review some potentially fruitful approaches to understanding cancer and its treatment. This includes the new paradigm of cancer that was developed over the last 15 years by Michael Retsky, Michael Baum, Romano Demicheli, Isaac Gukas, William Hrushesky and their colleagues on the basis of earlier pioneering work of Bernard Fisher and Judah Folkman. Next, we highlight the unique and pivotal role of mathematical modeling in testing biomedical hypotheses about the natural history of cancer and the effects of its treatment, elaborate on model selection criteria, and mention some methodological pitfalls. Finally, we describe a specific mathematical model of cancer progression that supports all the main postulates of the new paradigm of cancer when applied to the natural history of a particular breast cancer patient and fit to the observables. PMID- 24212621 TI - Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life/Death Decisions by Tumor Cells with Potential Clinical Applications. AB - Parathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal- as well as midregion- and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treatment. In particular, interest has mainly been focused on the effects of PTHrP on cell proliferation/apoptosis, migration and invasion, which are the main roles involved in cancer development in vivo. The objective of this review is to discuss collectively the literature data on the molecular and biochemical basis of the mechanisms underlying the different, and sometimes opposite, effects exerted by PTHrP on various neoplastic cytotypes, with some final comments on both present and potential utilization of PTHrP as a target for anti-cancer therapy. PMID- 24212620 TI - Pancreatic cancer gene therapy: from molecular targets to delivery systems. AB - The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets-both protein coding and non-coding-are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed. PMID- 24212622 TI - Cancer stem cells in head and neck cancer. AB - Head and neck cancer (HNC) is the sixth most common malignancy world-wide, however the survival rate has not improved for the past 20 years. In recent years, the cancer stem cell (CSC) hypothesis has gained ground in several malignancies and there is mounting evidence suggesting CSCs mediate tumor resistance to chemotherapy and radiation therapy. However, the CSC theory is also challenged at least in certain types of cancer. Here we review the progress of CSC studies in HNC, which suggest that HNC conforms to the CSC model. The identified CSC markers and their tumor initiation properties provide a framework for the development of novel therapeutic strategies for HNC. PMID- 24212623 TI - Progress in nanotechnology based approaches to enhance the potential of chemopreventive agents. AB - Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have been proposed as chemopreventive agents. These agents have proven excellent anticancer potential in the laboratory setting, however, the observed effects in vitro do not translate in clinic where they fail to live up to their expectations. Among the various reasons for this discrepancy include inefficient systemic delivery and robust bioavailability. To overcome this barrier, researchers have focused towards coupling these agents with nano based encapsulation technology that in principle will enhance bioavailability and ultimately benefit clinical outcome. The last decade has witnessed rapid advancement in the development of nanochemopreventive technology with emergence of many nano encapsulated formulations of different dietary anticancer agents. This review summarizes the most up-to-date knowledge on the studies performed in nanochemoprevention, their proposed use in the clinic and future directions in which this field is heading. As the knowledge of the dynamics of nano encapsulation evolves, it is expected that researchers will bring forward newer and far more superior nanochemopreventive agents that may become standard drugs for different cancers. PMID- 24212624 TI - Metabolic disorder, inflammation, and deregulated molecular pathways converging in pancreatic cancer development: implications for new therapeutic strategies. AB - Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3beta (GSK3beta) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3beta has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3beta inhibition alone or in combination with chemotherapy and radiation. GSK3beta inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation. PMID- 24212625 TI - Extra-neural metastases of malignant gliomas: myth or reality? AB - Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years-despite debulking surgery, radiotherapy and cytotoxic chemotherapy-with a median survival of 9-12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases. PMID- 24212626 TI - Diagnostic management of pancreatic cancer. AB - Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used. PMID- 24212627 TI - Nerve growth factor in cancer cell death and survival. AB - One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer. PMID- 24212629 TI - Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia. AB - Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed. PMID- 24212630 TI - Experimental animal models of pancreatic carcinogenesis for prevention studies and their relevance to human disease. AB - Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5' CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention. PMID- 24212631 TI - Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer. AB - Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic. PMID- 24212628 TI - Protein kinase C: an attractive target for cancer therapy. AB - Apoptosis plays an important role during all stages of carcinogenesis and the development of chemoresistance in tumor cells may be due to their selective defects in the intracellular signaling proteins, central to apoptotic pathways. Consequently, many studies have focused on rendering the chemotherapy more effective in order to prevent chemoresistance and pre-clinical and clinical data has suggested that protein kinase C (PKC) may represent an attractive target for cancer therapy. Therefore, a complete understanding of how PKC regulates apoptosis and chemoresistance may lead to obtaining a PKC-based therapy that is able to reduce drug dosages and to prevent the development of chemoresistance. PMID- 24212632 TI - Treatment resistance mechanisms of malignant glioma tumor stem cells. AB - Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed. PMID- 24212633 TI - Current surgical aspects of palliative treatment for unresectable pancreatic cancer. AB - Despite all improvements in both surgical and other conservative therapies, pancreatic cancer is steadily associated with a poor overall prognosis and remains a major cause of cancer mortality. Radical surgical resection has been established as the best chance these patients have for long-term survival. However, in most cases the disease has reached an incurable state at the time of diagnosis, mainly due to the silent clinical course at its early stages. The role of palliative surgery in locally advanced pancreatic cancer mainly involves patients who are found unresectable during open surgical exploration and consists of combined biliary and duodenal bypass procedures. Chemical splanchnicectomy is another modality that should also be applied intraoperatively with good results. There are no randomized controlled trials evaluating the outcomes of palliative pancreatic resection. Nevertheless, data from retrospective reports suggest that this practice, compared with bypass procedures, may lead to improved survival without increasing perioperative morbidity and mortality. All efforts at developing a more effective treatment for unresectable pancreatic cancer have been directed towards neoadjuvant and targeted therapies. The scenario of downstaging tumors in anticipation of a future oncological surgical resection has been advocated by trials combining gemcitabine with radiation therapy or with the tyrosine kinase inhibitor erlotinib, with promising early results. PMID- 24212634 TI - Palliative interventional and surgical therapy for unresectable pancreatic cancer. AB - Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually. PMID- 24212635 TI - Ras Isoprenylation and pAkt Inhibition by Zoledronic Acid and Fluvastatin Enhances Paclitaxel Activity in T24 Bladder Cancer Cells. AB - BACKGROUND: Bisphosphonates interfere with the mevalonate pathway and inhibit the prenylation of small GTP-binding proteins such as ras and rap. We hypothesized that zoledronic acid would synergistically inhibit T24 bladder cancer cell growth in combination with fluvastatin and paclitaxel. METHODS: Increasing doses of fluvastatin, zoledronic acid, and paclitaxel were investigated as single agents and in combination, and synergistic interactions were evaluated by the Chou Talalay method. Western blots were used to assess effects on signal transduction pathways. RESULTS: Growth of T24 was significantly inhibited with IC50 values of 2.67 +/- 0.61 mM for fluvastatin and 5.35 +/- 1.35 mM for zoledronic acid after 72 hours treatment. Geranylgeranyl pyrophosphate and farnesyl pyrophosphate was able to block, in part, this inhibitory activity. The combinations of zoledronic acid and paclitaxel, zoledronic acid and fluvastatin, and fluvastatin and paclitaxel were all synergistic. Both fluvastatin and zoledronic acid inhibited Ras and Rap prenylation, and the phosphorylation of ERK1/2 and AKT. The degree of inhibition of phosphorylation of these key signaling transduction pathways appears to closely correlate with their synergistic interactions. CONCLUSIONS: Zoledronic acid enhances fluvastatin and paclitaxel activity against T24 in a synergistic manner and this is mediated largely by inhibition of both the Ras/Raf/MEK/ERK and PI3K/AKT signaling pathways via isoprenylation inhibition. PMID- 24212636 TI - Treatment of pancreatic cancer: what can we really predict today? AB - Managing pancreatic cancer remains a big challenge due to its worse course and prognosis. However, therapeutic options and multimodal strategies are increasing nowadays, including new agents, new regimens and chemoradiation. Recently, the FOLFIRINOX regimen has been reported to be more active than gemcitabine in selected metastatic patients. In this setting, it will be of utmost interest to guide our therapeutic choice not only on clinical and pathological findings, but also on specific biomarkers that will predict tumor behavior and patient outcome (prognostic markers), and benefit from specific agents or regimens (predictive markers). In the near future, we will have to build both our therapeutic interventions and our clinical research based on an accurate patients' clinical selection and on biomolecular markers. In this review, we aimed to highlight and discuss some of the recent results reported on biomarkers in pancreatic cancer that may predict, i.e., preferential metastatic diffusion after surgery, like CXCR4, or predict gemcitabine efficacy in an adjuvant setting as well as in advanced disease, like hENT1. An important effort for translational research in pancreatic cancer research is thus required to validate such markers, while some important questions concerning tissue availability and processing, methodology of analysis, and design of future prospective trials, need to be addressed. PMID- 24212637 TI - Involvement of COUP-TFs in Cancer Progression. AB - The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis. COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression. Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial. In this review, we report both in vitro and in vivo data describing known and suspected actions of COUP-TFs that suggest that these factors are involved in modification of the phenotype of cancer cells, notably of epithelial origin. PMID- 24212638 TI - Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape? AB - According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed "cure" following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma. PMID- 24212640 TI - A Methodological Framework for Evaluating the Evidence for Complementary and Alternative Medicine (CAM) for Cancer. AB - In spite of lacking evidence for effects on cancer progression itself, an increasing number of cancer patients use various types of complementary and alternative medicine (CAM). There is disagreement between CAM practitioners, researchers and clinical oncologists, as to how evidence concerning effects of CAM can and should be produced, and how the existing evidence should be interpreted. This represents a considerable challenge for oncologists; both in terms of patient needs for an informed dialogue regarding CAM, and because some types of CAM may interact with standard treatments. There is a need for insight into which kinds of CAM may work, for whom they work, what the possible effects and side-effects are, and in what ways such effects may come about. The present article presents a framework for evaluating effects of CAM by suggesting a taxonomy of different levels of evidence related to different types of research questions and discussing the relevance of different research methodologies for different types of effects. PMID- 24212639 TI - Recently identified biomarkers that promote lymph node metastasis in head and neck squamous cell carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous cancer that arises in the upper aerodigestive tract. Despite advances in knowledge and treatment of this disease, the five-year survival rate after diagnosis of advanced (stage 3 and 4) HNSCC remains approximately 50%. One reason for the large degree of mortality associated with late stage HNSCC is the intrinsic ability of tumor cells to undergo locoregional invasion. Lymph nodes in the cervical region are the primary sites of metastasis for HNSCC, occurring before the formation of distant metastases. The presence of lymph node metastases is strongly associated with poor patient outcome, resulting in increased consideration being given to the development and implementation of anti-invasive strategies. In this review, we focus on select proteins that have been recently identified as promoters of lymph node metastasis in HNSCC. The discussed proteins are involved in a wide range of critical cellular functions, and offer a more comprehensive understanding of the factors involved in HNSCC metastasis while additionally providing increased options for consideration in the design of future therapeutic intervention strategies. PMID- 24212641 TI - Mastic oil inhibits the metastatic phenotype of mouse lung adenocarcinoma cells. AB - Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01-0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis. PMID- 24212643 TI - Molecular endoscopic ultrasound for diagnosis of pancreatic cancer. AB - Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound guided fine needle aspiration-biopsy in managing pancreatic cancer. PMID- 24212644 TI - Components of cell-matrix linkage as potential new markers for prostate cancer. AB - Prostate cancer is one of the most common tumor diseases worldwide. Often being non-aggressive, prostate tumors in these cases do not need immediate treatment. However, about 20% of diagnosed prostate cancers tend to metastasize and require treatment. Existing diagnostic methods may fail to accurately recognize the transition of a dormant, non-aggressive tumor into highly malignant prostate cancer. Therefore, new diagnostic tools are needed to improve diagnosis and therapy of prostate carcinoma. This review evaluates existing methods to diagnose prostate carcinoma, such as the biochemical marker prostate-specific antigen (PSA), but also discusses the possibility to use the altered expression of integrins and laminin-332 in prostate carcinomas as diagnostic tools and therapeutic targets of prostate cancer. PMID- 24212642 TI - Growth factor mediated signaling in pancreatic pathogenesis. AB - Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed. PMID- 24212645 TI - Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer. AB - Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer. PMID- 24212646 TI - Protein kinase a in cancer. AB - In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors. PMID- 24212647 TI - Inflammation and tumor microenvironment in lymph node metastasis. AB - In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis). Herein, principally reviewing experimental and clinical data related to malignant melanoma, we discuss diverse factors that are mechanistically involved in LN metastasis. We highlight recent data that link tumor microenvironment, including inflammation (at the cellular and cytokine levels) and tumor-induced lymphangiogenesis, with nodal metastasis. Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites. These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers. PMID- 24212648 TI - An evolutionary explanation for the perturbation of the dynamics of metastatic tumors induced by surgery and acute inflammation. AB - Surgery has contributed to unveil a tumor behavior that is difficult to reconcile with the models of tumorigenesis based on gradualism. The postsurgical patterns of progression include unexpected features such as distant interactions and variable rhythms. The underlying evidence can be summarized as follows: (1) the resection of the primary tumor is able to accelerate the evolution of micrometastasis in early stages, and (2) the outcome is transiently opposed in advanced tumors. The objective of this paper is to give some insight into tumorigenesis and surgery-related effects, by applying the concepts of the evolutionary theory in those tumor behaviors that gompertzian and tissular centered models are unable to explain. According to this view, tumors are the consequence of natural selection operating at the somatic level, which is the basic mechanism of tumorigenesis, notwithstanding the complementary role of the intrinsic constrictions of complex networks. A tumor is a complicated phenomenon that entails growth, evolution and development simultaneously. So, an evo-devo perspective can explain how and why tumor subclones are able to translate competition from a metabolic level into neoangiogenesis and the immune response. The paper proposes that distant interactions are an extension of the ecological events at the local level. This notion explains the evolutionary basis for tumor dormancy, and warns against the teleological view of tumorigenesis as a process directed towards the maximization of a concrete trait such as aggressiveness. PMID- 24212649 TI - Muscarinic receptor signaling in colon cancer. AB - According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer. PMID- 24212650 TI - Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-beta (TGF-beta) Signaling in Cancer. AB - Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-beta (TGF-beta), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-beta signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-beta signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression. PMID- 24212651 TI - Role of p53 in Cell Death and Human Cancers. AB - p53 is a nuclear transcription factor with a pro-apoptotic function. Since over 50% of human cancers carry loss of function mutations in p53 gene, p53 has been considered to be one of the classical type tumor suppressors. Mutant p53 acts as the dominant-negative inhibitor toward wild-type p53. Indeed, mutant p53 has an oncogenic potential. In some cases, malignant cancer cells bearing p53 mutations display a chemo-resistant phenotype. In response to a variety of cellular stresses such as DNA damage, p53 is induced to accumulate in cell nucleus to exert its pro-apoptotic function. Activated p53 promotes cell cycle arrest to allow DNA repair and/or apoptosis to prevent the propagation of cells with serious DNA damage through the transactivation of its target genes implicated in the induction of cell cycle arrest and/or apoptosis. Thus, the DNA-binding activity of p53 is tightly linked to its tumor suppressive function. In the present review article, we describe the regulatory mechanisms of p53 and also p53 mediated therapeutic strategies to cure malignant cancers. PMID- 24212652 TI - Targets and mechanisms of photodynamic therapy in lung cancer cells: a brief overview. AB - Lung cancer remains one of the most common cancer-related causes of death. This type of cancer typically develops over a period of many years, and if detected at an early enough stage can be eliminated by a variety of treatments including photodynamic therapy (PDT). A critical discussion on the clinical applications of PDT in lung cancer is well outside the scope of the present report, which, in turn focuses on mechanistic and other aspects of the photodynamic action at a molecular and cellular level. The knowledge of these issues at pre-clinical levels is necessary to develop, check and adopt appropriate clinical protocols in the future. This report, besides providing general information, includes a brief overview of present experimental PDT and provides some non-exhaustive information on current strategies aimed at further improving the efficacy, especially in regard to lung cancer cells. PMID- 24212653 TI - Cell-centric view of apoptosis and apoptotic cell death-inducing antitumoral strategies. AB - Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies. PMID- 24212654 TI - Gold nanostructures as a platform for combinational therapy in future cancer therapeutics. AB - The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID- 24212655 TI - Drug treatment of cancer cell lines: a way to select for cancer stem cells? AB - Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs. PMID- 24212656 TI - Genetic alterations in glioma. AB - Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes. PMID- 24212657 TI - Retrotransposon-encoded reverse transcriptase in the genesis, progression and cellular plasticity of human cancer. AB - LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti cancer therapy. PMID- 24212658 TI - Implication of heat shock factors in tumorigenesis: therapeutical potential. AB - Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of "non classical" targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non cogenic potential of these HSFs, more specifically associated to the activation of "non-classical" HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents. PMID- 24212659 TI - Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways. AB - The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e., atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas as well as small-cell and squamous cell lung cancer cells in cell culture. In vivo, these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers growing in athymic mice. Their signaling in cancer cells includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the MEK 1/2 kinases and 97% inhibition of the activation of basal activity of the ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. They also completely block the activity of mitogens such as epidermal growth factor's ability to stimulate ERK and Ras. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunocytochemical studies to inhibit DNA synthesis within cancer cells. PMID- 24212660 TI - Current state of surgical management of pancreatic cancer. AB - Pancreatic cancer is still associated with a poor prognosis and remains-as the fourth leading cause of cancer related mortality-a therapeutic challenge. Overall long-term survival is about 1-5%, and in only 10-20% of pancreatic cancer patients is potentially curative surgery possible, increasing five-year survival rates to approximately 20-25%. Pancreatic surgery is a technically challenging procedure and has significantly changed during the past decades with regard to technical aspects as well as perioperative care. Standardized resections can be carried out with low morbidity and mortality below 5% in high volume institutions. Furthermore, there is growing evidence that also more extended resections including multivisceral approaches, vessel reconstructions or surgery for tumor recurrence can be carried out safely with favorable outcomes. The impact of adjuvant treatment, especially chemotherapy, has increased dramatically within recent years, leading to significantly improved postoperative survival, making pancreatic cancer therapy an interdisciplinary approach to achieve best results. PMID- 24212661 TI - The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status. AB - The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 +/- 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21- combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21- carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status. PMID- 24212662 TI - Glutathione in cancer cell death. AB - Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy. PMID- 24212663 TI - Cancer stem cells in breast cancer. AB - The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities. In this review, we focus on recent reports regarding the identification of CSC markers and the molecular mechanism of CSC phenotypes to understand the basic properties and molecular target of CSCs. In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease. The identification of CSC markers and an improved understanding of the molecular mechanism of CSC phenotypes should lead to progress in cancer therapy and improved prognoses for patients with cancer. PMID- 24212664 TI - The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis. AB - Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF kappaB. Blockage of NF-kappaB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL. PMID- 24212665 TI - Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. AB - Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects. PMID- 24212666 TI - Breast cancer-initiating cells: insights into novel treatment strategies. AB - There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24-/low and/or CD133+ expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways. PMID- 24212668 TI - Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report. AB - The present article describes the ongoing (partial) remission of a female patient (41 years old) from estrogen receptor (ER)-positive/progesterone receptor (PR) negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation), the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and 18FDG-PET-CT plus magnetic resonance (MR) imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated. PMID- 24212669 TI - Overexpression of CYP3A4 in a COLO 205 Colon Cancer Stem Cell Model in vitro. AB - Cancer stem cells (CSCs) seem to constitute a subpopulation of tumor cells that escape from chemotherapy and cause recurrent disease. Low proliferation rates, protection in a stem cell niche and overexpression of drug resistance proteins are considered to confer chemoresistance. We established an in vitro colon CSC like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium. Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR. ALDH1A1 is a CSC marker for certain tumor entities and confers resistance to cyclophosphamide. CYP3A4 is expressed in liver and colon and its overexpression seems particularly relevant in colon cancer, since it inactivates irinotecan and other xenobiotics, such as taxols and vinca alkaloids. In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients. PMID- 24212667 TI - The role of epigenetics in resistance to Cisplatin chemotherapy in lung cancer. AB - Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. PMID- 24212670 TI - Memory recall and modifications by activating neurons with elevated CREB. AB - Memory is supported by a specific ensemble of neurons distributed in the brain that form a unique memory trace. We previously showed that neurons in the lateral amygdala expressing elevated levels of cAMP response-element binding protein are preferentially recruited into fear memory traces and are necessary for the expression of those memories. However, it is unknown whether artificially activating just these selected neurons in the absence of behavioral cues is sufficient to recall that fear memory. Using an ectopic rat vanilloid receptor TRPV1 and capsaicin system, we found that activating this specific ensemble of neurons was sufficient to recall established fear memory. Furthermore, this neuronal activation induced a reconsolidation-like reorganization process, or strengthening of the fear memory. Thus, our findings establish a direct link between the activation of specific ensemble of neurons in the lateral amygdala and the recall of fear memory and its subsequent modifications. PMID- 24212671 TI - Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus. AB - Using immunohistology, electron microscopy, electrophysiology and optogenetics, we found that proliferating adult mouse hippocampal neural precursors received immature GABAergic synaptic inputs from parvalbumin-expressing interneurons. Recently shown to suppress adult quiescent neural stem cell activation, parvalbumin interneuron activation promoted newborn neuronal progeny survival and development. Our results suggest a niche mechanism involving parvalbumin interneurons that couples local circuit activity to the diametric regulation of two critical early phases of adult hippocampal neurogenesis. PMID- 24212672 TI - Attention modulates spatial priority maps in the human occipital, parietal and frontal cortices. AB - Computational theories propose that attention modulates the topographical landscape of spatial 'priority' maps in regions of the visual cortex so that the location of an important object is associated with higher activation levels. Although studies of single-unit recordings have demonstrated attention-related increases in the gain of neural responses and changes in the size of spatial receptive fields, the net effect of these modulations on the topography of region level priority maps has not been investigated. Here we used functional magnetic resonance imaging and a multivariate encoding model to reconstruct spatial representations of attended and ignored stimuli using activation patterns across entire visual areas. These reconstructed spatial representations reveal the influence of attention on the amplitude and size of stimulus representations within putative priority maps across the visual hierarchy. Our results suggest that attention increases the amplitude of stimulus representations in these spatial maps, particularly in higher visual areas, but does not substantively change their size. PMID- 24212673 TI - Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans. AB - Prior to the advent of synthetic nematocides, natural products such as seaweed were used to control nematode infestations. The nematocidal agent in seaweed is betaine, an amino acid that functions as an osmolyte and methyl donor. However, the molecular mechanisms of betaine toxicity are unknown. We identified the betaine transporter SNF-3 and the betaine receptor ACR-23 in the nematode C. elegans. Mutating snf-3 in a sensitized background caused the worms to be hypercontracted and paralyzed, presumably as a result of excess extracellular betaine. These behavioral defects were suppressed by mutations in acr-23, which encodes a ligand-gated cation channel of the cys-loop family. ACR-23 was activated by betaine and functioned in the mechanosensory neurons to maintain basal levels of locomotion. However, overactivation of the receptor by excess betaine or by the allosteric modulator monepantel resulted in hypercontraction and death of the nematode. Thus, monepantel targets a betaine signaling pathway in nematodes. PMID- 24212674 TI - Independent hypothalamic circuits for social and predator fear. AB - The neural circuits mediating fear to naturalistic threats are poorly understood. We found that functionally independent populations of neurons in the ventromedial hypothalamus (VMH), a region that has been implicated in feeding, sex and aggression, are essential for predator and social fear in mice. Our results establish a critical role for VMH in fear and have implications for selective intervention in pathological fear in humans. PMID- 24212675 TI - Searching for optimal rating scales in the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). AB - The comparison of the performance of the numerical rating scale (NRS) versus visual analog scale (VAS) in the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) showed that the 11-point NRS is psychometrically superior to the 10-cm VAS. This finding is in agreement with previous studies and the recommendation by the Assessment of SpondyloArthritis international Society. To illustrate the functioning of the response categories of both BASFI and BASDAI, we analyzed the rating scales (using the Rasch rating scale model) in patients with ankylosing spondylitis. Our results have shown that the 11 categories available in the 0-10 NRS version of both BASFI and BASDAI exceed the number of levels of a construct that participants can discriminate. This indicates the need for improving the metric quality of both rating scales by appropriately reducing the number of categories. PMID- 24212676 TI - Associations of the PTPN22 and CTLA-4 genetic polymorphisms with Taiwanese ankylosing spondylitis. AB - Ankylosing spondylitis (AS) is an autoimmune disease, and the imbalance of peripheral tolerance is involved in its pathogenesis. Importantly, the negative signal of activated T cells plays a crucial role in the balance of peripheral tolerance. It has been postulated that human protein tyrosine phosphatase nonreceptor 22 (PTPN22) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes encode proteins that are actively involved in regulating T-cell activation. Therefore, we evaluated the effects of PTPN22 and CTLA-4 genotypes on the occurrence of AS. Genetic polymorphisms of PTPN22 -1123G/C and CTLA-4 +49A/G were identified by polymerase chain reaction for 391 AS patients and 391 healthy controls. Subjects with PTPN22 CC and GC genotypes had a greater risk of AS occurrence than those with PTPN22 GG genotype [relative risk = 1.39, 95 % confidence interval (95 % CI) 1.03-1.88]. Further, subjects with PTPN22 CC/CTLA-4 AA or PTPN22 GC/CTLA-4 AA genotypes had 1.90-fold (95 % CI 1.02-3.49) greater risk of AS development than those with other combinations of PTPN22 and CTLA-4 genotypes. Our findings indicated that PTPN22 -1123G/C and CTLA-4 +49A/G genetic polymorphisms have a combined effect on the development of AS. PMID- 24212678 TI - Zooplankton induced changes in dissolved free amino acids and in production rates of freshwater bacteria. AB - This study examined the importance of zooplankton in the flux of dissolved free amino acids (DFAA) in the water and into bacteria. DFAA release rates were followed in laboratory grazing experiments usingDaphnia galeata andEudiaptomus graciloides as grazers, andScenedesmus acutus andSynechococcus elongatus as food sources. Except for minor initial peaks, DFAAs were released continuously during the first 2 hours and made up 6-12% (in one experiment 50%) of the calculated ingestion rates. During three diel studies in lakes, effects of removal and increase of the density of zooplankton (>200MUm) on the pools of DFAA as well as on the bacterial production were followed. During two of the diel studies, higher DFAA pools were measured when 3-4 times the natural zooplankton density was present, and in one study a minor increase also occurred in the bacterial production, compared with results from experiments without zooplankton and with a natural zooplankton density. The increase in bacterial growth coincided with a decline in DFAA. During the third study, neither DFAA nor the bacterial production changed significantly when the zooplankton density was increased 3 times. Removal of zooplankton, however, caused a decline in both DFAA and bacterial production. Our data suggest a close relationship between occurrence of zooplankton and release of DFAA, but the factors regulating the amount of DFAA released and its effect on bacterial growth are not yet understood. PMID- 24212677 TI - Association between vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus: a meta-analysis. AB - Association studies of vitamin D receptor (VDR) gene polymorphisms and the risk of systemic lupus erythematosus (SLE) have yielded conflicting results in different backgrounds. We aimed to evaluate the association between VDR gene polymorphisms and SLE risk. A predefined electronic databases search was performed to identify eligible studies that were related to the association of VDR gene BsmI, FokI, ApaI or TaqI polymorphism with SLE risk. Either a fixed effects model, or in the presence of heterogeneity, a random-effects model was used to calculate the pooled odds ratios (ORs) and its corresponding 95% confidence interval (CI). A total of 11 studies with 1,621 cases and 1,883 controls were included in this meta-analysis. BsmI B allele was associated with the onset of SLE for overall populations (OR 1.726, 95% CI 1.214-2.455) and Asians (OR 1.952, 95% CI 1.135-3.355). FokI FF genotype was correlated with the susceptibility of SLE for Asians (OR 1.469, 95% CI 1.005-2.148). FokI T/C and TaqI polymorphisms were not associated with SLE risk for Caucasians. There was no significant association between ApaI polymorphism and SLE risk for overall populations, Asians and Caucasians. No evidence of publication bias was observed. In conclusion, BsmI B allele may be a risk factor for SLE onset among overall populations and Asians, and FokI FF genotype is a risk factor for SLE susceptibility in Asians. However, more studies should be performed in the future. PMID- 24212679 TI - Bacterial productivity in ponds used for culture of penaeid prawns. AB - The quantitative role of bacteria in the carbon cycle of ponds used for culture of penaeid prawns has been studied. Bacterial biomass was measured using epifluorescence microscopy and muramic acid determinations. Bacterial growth rates were estimated from the rate of tritiated thymidine incorporation into DNA. In the water column, bacterial numbers ranged from 8.3*10(9) 1(-1) to 2.57*10(10) 1(-1) and production ranged from 0.43 to 2.10 mg Cl(-1) d(-1). In the 0-10 mm zone in sediments, bacterial biomass was 1.4 to 5.8 g C m(-2) and production was 250 to 500 mg C m(-2) d(-1). The results suggested that most organic matter being supplied to the ponds as feed for the prawns was actually being utilized by the bacteria. When the density of meiofauna increased after chicken manure was added, bacterial biomass decreased and growth rates increased. PMID- 24212680 TI - Diel changes in the specific growth rate and mean cell volume of natural bacterial communities in two different water masses in the Irish sea. AB - Diel changes in the specific growth rates of natural bacterial communities as a whole and of different groups within the communities were followed over 2 days during July 1982, in stratified waters in the vicinity of a shallow sea tidal mixing front in the Irish Sea. Waters well above (4 m) and below (60 m) the thermocline were enclosed in dialysis bags and incubated in situ. The results show that there were periods of altered growth rates of the whole bacterial community and synchronous cell division of morphological groups. An increase in mean cell volume within both 4 and 60 m communities preceded an increase in specific growth rates, with a resultant decrease in the mean cell volume. Above the thermocline the whole bacterial community, as well as the rod and coccoid forms, doubled in number once a day. The doubling time of the whole bacterial community at 60 m was 2 days and slower than that at 4 m. This was due to a slower doubling time (3 days) for the coccoid forms. Rod forms at the two depths had a similar doubling time (1 day). The time of day when maximum division rate occurred was also different in the two water masses. At 4 m more coccoid forms divided during the night, whereas at 60 m more divided during the day. Conversely, at 4 m more rod forms divided during the day, whereas at 60 m more divided at night.These data indicate that the bacterial community and members of the community may be adapted to exploit the diurnal rhythms of dissolved organic carbon (DOC) release by other organisms and that portions of the bacterial community may therefore be more active at certain times of the day. The diurnal growth of the bacterial community may thus vary between different water masses and largely reflects the differences in the chemical and biological characteristics of the two water masses investigated. PMID- 24212681 TI - Nitrate reduction activity in a continuous flow-through system in marine sediments. AB - Nitrate reduction in a non-polluted, coastal marine sediment was measured with an open flow-through system. The recorded rates depended upon nitrate concentration but were largely independent of the weight of sediment (14-35 g) and the dilution rate (0.7-5 h(-1)). Rate of nitrate uptake followed classical Michaelis-Menten kinetics, and km and Vmax values were equal to 78MUM and 0.168MUm mol g(-1) hour( 1), respectively. These values are in good agreement with those found by the other authors for the same biotope but by different methods. This technique of the open flow-through system is fast, simple, and inexpensive and involves small quantities of sediment (~10 g). PMID- 24212682 TI - Temporal relationship between the deposition and microbial degradation of lignocellulosic detritus in a Georgia salt marsh and the Okefenokee Swamp. AB - Temperature dependence and seasonal variations in rates of microbial degradation of the lignin and polysaccharide components of specifically radiolabeled lignocelluloses were determined in sediment and water samples from a Georgia salt marsh and the nearby Okefenokee Swamp. Although temperature regimes in the two ecosystems were similar, rates of mineralization ofSpartina alterniflora lignocellulose in salt marsh sediments increased eightfold between winter and summer, whereas rates of mineralization of lignocellulose from an analogous freshwater macrophyte,Carex walteriana, in Okefenokee sediments increased only twofold between winter and summer. Temperature was the major factor influencing seasonal variations in rates of lignocellulose degradation in both environments. At any given temperature, no substantial differences in lignocellulolytic potential were observed with sediment samples collected at each season. In both ecosystems, the bulk of the lignocellulosic detritus was not degraded at the time of its peak deposition during the fall and winter. Instead, the periods of maximal decomposition occurred during the following spring and summer. These results suggest that periods of maximal nutrient regeneration from the mineralization of lignocellulosic detritus coincide with periods of highest primary production, and that, depending on hydrologic conditions, significant horizontal transport of essentially intact lignocellulosic material is possible due to the lag period between deposition and microbial degradation. PMID- 24212683 TI - Growth kinetics ofPseudomonas fluorescens microcolonies within the hydrodynamic boundary layers of surface microenvironments. AB - Computer-enhanced microscopy (CEM) was used to study the growth kinetics of bacterial microcolonies attached to the wall of a continuous-flow slide culture. Image processing increased effective microscope resolution and quantitated colony growth at 10 min intervals. Three growth parameters were used to determine growth rate: the time required for cell fission, the specific rate of increase in cell number, and the specific rate of increase in cell area. Growth rate was initially constant regardless of colony size, as assumed previously in deriving colonization kinetics. However, at low substrate concentrations growth rate varied depending on laminar flow velocity. Growth was flow-dependent at a glucose concentration of 100 mg/liter and flow-independent at a concentration of 1 g/liter. This indicated that the surface microenvironment became substrate depleted in the absence of sufficient laminar flow velocities and that glucose rather than oxygen was rate limiting. PMID- 24212684 TI - The influence of fish culture in floating net cages on microbial indicators of water quality. AB - This work was carried out to analyse the microbiological parameters of the water quality of a reservoir used for the irrigation and culture of tilapia (Oreochromis niloticus) in floating net cages. The physico-chemical parameters, counts of mesophilic total aerobic bacteria, total and thermotolerant coliforms and fecal streptococci, and the presence of Escherichia coli in samples of water collected in three sites of the reservoir (pre-culture site, culture site, post culture site) were analysed. The levels of ammonia (0.047-0.059 mg/L), nitrite (0.001-0.021 mg/L) and total phosphorus (0.050-0.355 mg/L) in the water did not show significant differences (p > 0.05) between sampling sites. The levels of total bacteria in the water varied between 1.3 x 10(4) and 67.3 x 10(4) CFU/100 mL. The MPN values of thermotolerant coliforms (< 930 MPN/100 mL) were within values recommended for water used for fish culture and/or irrigation. The presence of E. coli and fecal streptococci were verified in 48% and 56% of analysed samples, respectively. The site with floating net cages showed more samples contaminated with E. coli and fecal streptococci than other sampling points. PMID- 24212685 TI - Nestedness in forest mammals is dependent on area but not on matrix type and sample size: an analysis on different fragmented landscapes. AB - Nestedness, the pattern in which the species of a species-poor community are a subset of species-rich communities, can provide information regarding species order of extinction, which is vital knowledge for conservation biology. We tested the hypotheses that the nestedness of mammal communities in forest remnants is influenced by sampling effort, mean remnant area, range of remnant areas, matrix type, and presence or absence of forest corridors, and compared the results with multi-taxa reviews. We used 24 published datasets to test this hypothesis and ran simple regressions for each variable. Our results provide evidence that area was the main determinant of nestedness in mammalian communities. We also found a significant effect on the range of areas as measured through area ratio. However we conclude that nestedness is not affected by sample size. PMID- 24212686 TI - Ecosystem Services of UHE Carlos Botelho (Lobo/Broa): a new approach for management and planning of dams multiple-uses. AB - The aim of this study was to identify and make an initial accounting of the ecosystem services of the hydroelectric power generation plant, UHE Carlos Botelho (Itirapina Municipality, Sao Paulo State, Brazil), and its most extensive wetlands--total of 2,640 ha--and also identify the drivers of change of these services. Twenty (20) ecosystem services were identified and the estimated quantitative total value obtained was USD 120,445,657.87. year(-1) or USD 45,623.35 ha(-1).year(-1). Investments on restoration of spatial heterogeneity along Tiete-Jacare hydrographic basin and new technologies for regional economic activities must maintain ecological functions as well as increase marginal values of ecosystem services and the potential annual economic return of ecological functions. PMID- 24212687 TI - Diversity of the Arthropod edaphic fauna in preserved and managed with pasture areas in Teresina-Piaui-Brazil. AB - The soil fauna plays an important function over the processes of organic matter decomposition, nutrient cycling, ground aeration and fertility. Thus, studies on the composition and structure of such communities are important, considering moreover the lack of information in different regions of Brazil and mainly related to the state of Piaui. This study aimed to evaluate the density and diversity of the soil arthropod fauna in a Cerrado area in preservation conditions and in a pasture area. Both are situated in the city of Teresina, capital of the state of Piaui. Pitfall traps were used for sampling. Five stations with four traps were placed in each area. The traps were constituted by a 500 mL plastic cup containing a preserving solution made with 70% alcohol and 40% formalin. The traps were weekly changed by occasion of the collections. Eight samples were performed in the period between March and April 2007. The results were evaluated using the following variables: number of orders, number of families, total of species and total number of individuals. Evaluation of the Diversity Index and Similarity Coefficient were also performed. As result, the variables and diversity indices were slightly higher in the preserved area. However, the similarity coefficient showed only 10% similarity between both areas. PMID- 24212688 TI - Effects of isolation and environmental variables on fish community structure in the Brazilian Amazon Madeira-Purus interfluve. AB - Due to the existence of terrestrial barriers to freshwater fish dispersion, it is believed that its distribution is strongly associated with historical factors related to the formation of the habitats they occupy. By the other hand, some studies reveal the influence of abiotic conditions (such as size of water bodies, pH, conductivity) on the composition of fish fauna occurring in small streams. This study aimed to investigate whether drainage basins, because catchment boundaries are potential barriers to fish dispersion, or the physical structure and physico-chemical characteristics of water have a greater influence on fish community structure in small streams. We sampled 22 streams belonging to five drainage basins in the Madeira-Purus interfluve. Fish were caught with dip nets and a small trawl, and data were simultaneously obtained on structural characteristics of the streams and physico-chemical characteristics of the water. Community composition was analyzed using Non-Metric Multidimensional Scaling (NMDS), and variables related to structural and physico-chemical characteristics were summarized by Principal Component Analysis (PCA). Two explanatory models relating faunal composition to environmental factors were constructed: the first using only continuous variables and the second including the drainage basin as a categorical variable. The Akaike Information Criterion (AIC) and AIC weight were used to select the best model. Although structural and physico-chemical variables significantly contributed to explaining faunal composition, the model including the drainage basin was clearly the better of the two models (more than 90% support in the data). The importance of drainage basins in structuring fish communities in streams may have significant consequences for conservation planning in these environments. PMID- 24212689 TI - Antifouling activity of twelve demosponges from Brazil. AB - Benthic marine organisms are constantly exposed to fouling, which is harmful to most host species. Thus, the production of secondary metabolites containing antifouling properties is an important ecological advantage for sessile organisms and may also provide leading compounds for the development of antifouling paints. High antifouling potential of sponges has been demonstrated in the Indian and Pacific oceans and in the Caribbean and Mediterranean seas. Brazilian sponges remain understudied concerning antifouling activities. Only two scientific articles reported this activity in sponges of Brazil. The objective of this study was to test crude extracts of twelve species of sponges from Brazil against the attachment of the mussel Perna perna through laboratorial assays, and highlight promising species for future studies. The species Petromica citrina, Amphimedon viridis, Desmapsamma anchorata, Chondrosia sp., Polymastia janeirensis, Tedania ignis, Aplysina fulva, Mycale angulosa, Hymeniacidon heliophila, Dysidea etheria, Tethya rubra, and Tethya maza were frozen and freeze-dried before extraction with acetone or dichloromethane. The crude extract of four species significantly inhibited the attachment of byssus: Tethya rubra (p = 0.0009), Tethya maza (p = 0.0039), Petromica citrina (p = 0.0277), and Hymeniacidon heliophila (p = 0.00003). These species, specially, should be the target of future studies to detail the substances involved in the ability antifouling well as to define its amplitude of action. PMID- 24212690 TI - Community of orchid bees (Hymenoptera: Apidae) in transitional vegetation between Cerrado and Atlantic Forest in southeastern Brazil. AB - The community of orchid bees (Hymenoptera: Apidae: Euglossina) was studied at an area in the transition between the Cerrado and Atlantic Forest biomes, from March, 2010 to February, 2011 in the Barroso region, state of Minas Gerais, eastern Brazil. Orchid-bee males were collected with bait traps containing three different scents (cineole, eugenol and vanillin) and with entomological nets for collecting bees on flowers. A total of 614 orchid-bee males were collected using aromatic traps, belonging to four genera and 15 species. Twenty-five female specimens belonging to two genera and at least three species were collected on flowers. Eulaema (Apeulaema) nigrita Lepeletier, 1841 was the most abundant species (50% of collected specimens), followed by Euglossa (Euglossa) truncata Rebelo & Moure, 1996 (28%). Cineole was the most attractive compound (66.5% of males and 13 species), followed by eugenol (16% and 9 species) and vanillin (13.5% and 4 species). Eulaema (Apeulaema) marcii Nemesio, 2009 and Eufriesea auriceps (Friese, 1899) were attracted to all scents, whereas Euglossa species were collected only in cineole and eugenol. PMID- 24212691 TI - The orchid-bee fauna (Hymenoptera: Apidae) of 'RPPN Feliciano Miguel Abdala' revisited: relevant changes in community composition. AB - The orchid-bee fauna of 'Reserva Particular do Patrimonio Natural Feliciano Miguel Abdala', a 957-ha preserve of Atlantic Forest in eastern Minas Gerais, southeastern Brazil, was surveyed 12 years after the first inventory in the area. Orchid-bee males were actively collected with insect nets when attracted to seventeen chemical compounds used as scent baits. Three hundred and nineteen males belonging to nine species were collected during 40 hours in late December, 2011, when orchid bees are supposedly more active. Euglossa despecta Moure, 1968, one of the dominant species in the area 12 years ago, was not recorded in the present study. Eulaema nigrita Lepeletier, 1841, on the other hand, represented only 16% of the collected bees in 1999 and 61% in the present study. Possible causes and consequences of these changes are discussed. PMID- 24212692 TI - Characterization of Desmodus rotundus (E. Geoffroy, 1810) (Chiroptera, Phyllostomidae) shelters in the Municipality of Sao Pedro--SP. AB - Surveillance of hematophagous bats is an important public health measure for the prevention and control of rabies epidemics in domestic herbivorous animals. The aim of this study was to locate and georeference D.rotundus shelters in the Municipality of Sao Pedro - SP, Brazil, and verify their nature (artificial or natural), surrounding landscape and distance from main rivers. To do this, two samples were taken of populations in shelters, with an interval of six months between them, capturing all the bats existent in shelters with fewer than 20 individuals and approximately 20% of the bats present in shelters with over 20 individuals in order to quantify their gender and age distribution. The majority of D. rotundus (67%) were verified to be artificial and the remainder (33%) natural. Of the six artificial shelters found, five were located in abandoned houses and one in a rain water drainage channel. There were no signs of D. rotundus in other rural buildings and viaducts located in the proximities of pastures. In spite of the majority of D. rotundus shelters being artificial, the three most populated shelters were maternity colonies, two being located in grottos and only one in an artificial shelter (rain water drainage channel). The remaining shelters were occupied by only male individuals. With the exception of one shelter, all the other shelters were at a distance of less than 3 km from the main bodies of water in the study area, corroborating studies that have reported that the main rivers in the State of Sao Paulo are the main geographic features related to the presence of D. rotundus. It was also verified that 67% of the shelters were inhabited by only male individuals, which confirms other studies conducted in the State of Sao Paulo, in which over 60% of the groups of Desmodus contain only male individuals. PMID- 24212693 TI - Towards a standard framework to describe behaviours in the common-sloth (Bradypus variegatus Schinz, 1825): novel interactions data observed in distinct fragments of the Atlantic forest, Brazil. AB - The common three-toed sloth is a widespread species, but the location and the observation of its individuals are greatly hindered by its biological features. Their camouflaged pelage, its slow and quiet movements, and the strictly arboreal habits resulted in the publication of sparse, fragmented and not patterned information on the common sloth behaviour. Thus, herein we propose an updated standardized behavioural categories' framework to the study of the species. Furthermore we describe two never reported interaction behaviours: a probable mating / courtship ritual between male and female; and apparent recognition behaviour between two males. Finally we highlight the contribution of small duration field works in this elusive species ethological study. PMID- 24212694 TI - Habitat selection by anurofauna community at rocky seashore in coastal Atlantic Forest, Southeastern Brazil. AB - Rocky seashores are low granitic hills distributed along the southeastern Brazilian coast with xeric-like vegetation due to the shallow soil. Knowledge on amphibian communities and their reproductive patterns is especially reduced on this kind of environment. Herein, we present a framework of two years monitoring an amphibian community at a rocky seashore environment located at the protected area of Parque Estadual da Serra da Tiririca, municipality of Niteroi, state of Rio de Janeiro, Brazil. We conducted diurnal and nocturnal searches for frogs in tank bromeliads, rocky surface and shrubby vegetation. Annual pattern of breeding activity of anurans was also estimated. Individuals of the most abundant tank bromeliad, Alcantarea glaziouana were collected and measured according to several variables to understanding the selection of bromeliads by frogs. We checked the influence of the environmental conditions on amphibian abundance, association between the bromeliads measures, and the water storage in the tank. We recorded the species: Scinax aff. x-signatus; S. cuspidatus; S. littoreus; Thoropa miliaris and Gastrotheca sp. Bromeliads were the preferential habitat used by anurans. The nocturnal habit was predominant for all species and during diurnal searches, the specimens were found sheltered in bromeliads axils. The number of calling males as well as amphibian abundance was associated with the rainiest and warmest period of the year. The species S. littoreus was observed in breeding activity in the majority of sample period. Adult calling males of T. miliaris were observed especially in the rainy season. Rainfall and temperature combined are positively correlated to the total number of captured amphibians. However, individually, rainfall was not significantly correlated, while temperature was positively correlated with the amphibian abundance. Water storage capacity by bromeliads was correlated to characteristics and size of the plant. In the rainy season, the height of the plant and the diameter on top view were correlated with the occurrence of amphibians, while during the driest period there was no correlation among variables and the bromeliad usage by amphibians. Recorded species were strongly associated to the Atlantic Forest domain. Nevertheless, the occupation of rocky seashores by anurans may be more associated with the specialized reproductive modes presented by species, since there is no permanent water available in ponds or streams. PMID- 24212695 TI - Coleopterofauna found on fresh and frozen rabbit carcasses in Curitiba, Parana, Brazil. AB - Many arthropod species are associated with carrion and some of them can be used as forensic indicators in murder investigations to estimate the time of death. Different physical conditions of cadavers may influence the fauna and the importance of freezing and thawing is unknown. The present paper sought to survey the Coleoptera species encountered in frozen and fresh rabbit carcasses, at a forest in Curitiba, Brazil. Four rabbit carcasses, two of them fresh and the other frozen were used. The coleopterofauna was sampled daily, and analyzed using non-parametric tests. A total of 666 beetles were sampled, belonging to 28 species in 10 families. Most of the beetles captured were larvae of Oxelytrum spp. (433) which are known to be necrophagous. The two frozen carcasses accounted for most of the beetles (338 and 180) in comparison with the two fresh carcasses (103 and 45). The tests were based on the most abundant species. Oxelytrum spp. median differed significantly between carcasses (H = 12.47844; p = 0.0059). The two fresh carcasses differed significantly (U = 190.0; p = 0.00019), but there was no significant difference between the frozen carcasses (U = 336.0; p = 0.29755). The data indicate that the freezing process prevents certain species to colonize carcasses, in this case with the dominance of species of Oxelytrum. These data also indicate that careful attention is necessary before using frozen carcasses in forensic entomology studies. PMID- 24212696 TI - Longitudinal distribution of Chironomidae (Diptera) downstream from a dam in a neotropical river. AB - The damming of a river causes dangerous consequences on structure of the environment downstream of the dam, modifying the sediment composition, which impose major adjustments in longitudinal distribution of benthic community. The construction of Engenheiro Sergio Motta Dam in the Upper Parana River has caused impacts on the aquatic communities, which are not yet fully known. This work aimed to provide more information about the effects of this impoundment on the structure of Chironomidae larvae assemblage. The analysis of data of physical and chemical variables in relation to biological data of 8 longitudinal sections in the Upper Parana River showed that composition of Chironomidae larvae of stations near Engenheiro Sergio Motta Dam differed of the other stations (farther of the Dam). The predominance of coarse sediments at stations upstream and finer sediments further downstream affected the choice of habitat by different morphotypes of Chironomidae and it caused a change in the structure of this assemblage in the longitudinal stretch. PMID- 24212697 TI - Analysis of fishing activity in the Ita reservoir, Upper Uruguay River, in the period 2004-2009. AB - This study characterized fishing activity in the reservoir of the Hydroelectric Power Plant of Ita in Brazil. The reservoir is located in the Upper Uruguay River, which forms the border between the states of Santa Catarina and Rio Grande do Sul. To analyze fishing activity and the composition of ichthyofauna in the reservoir after damming, questionnaires were administered to fishermen in the region between 2004 and 2009. The results showed that fishing in the Ita reservoir can be classified as a subsistence activity performed on small vessels and usually involving the use of drift nets and handlines. Between 2004 and 2009, 292,780.10 kg worth of fish were captured, with an average annual productivity of 3.46 kg ha(-1) yr(-1). We recorded the highest values of catch per unit effort in 2006, with an annual average of 9.69 kg fisherman(-1) day(-1). A total of 27 morphospecies were captured during the sample period; carp, traira, mandi and jundia together accounted for almost 60% of the catch. This finding indicates that fishing is centered on the capture of sedentary and short-distance migratory species. Despite their lower abundance, long-distance migratory species continue to be captured. The case of the piracanjuba, a long-distance migratory species reintroduced to the region in 2004 and still present in the catches, is particularly noteworthy. Regarding the fishermen's socioeconomic profile, all were men, most of who have engaged in the activity for more than eleven years, have a low educational level, fish with the aid of family members and list agriculture as their main economic activity. PMID- 24212698 TI - Development of a benthic multimetric index for the Serra da Bocaina bioregion in Southeast Brazil. AB - Brazil faces a challenge to develop biomonitoring tools to be used in water quality assessment programs, but few multimetric indices were developed so far. This study is part of an effort to test and implement programs using benthic macroinvertebrates as bioindicators in Rio de Janeiro State. Our aim was first to test the Multimetric Index for Serra dos Orgaos (SOMI) for a different area- Serra da Bocaina (SB)--in the same ecoregion. We sampled 27 streams of different sizes and altitudes in the SB region. Despite the environmental similarities, results indicated biological differences between reference sites of the two regions. Considering these differences, we decided to develop an index specific for the SB region, the Serra da Bocaina Multimetric Index (MISB). We tested twenty-two metrics for sensitivity to impairment and redundancy, and six metrics were considered valid to integrate the MISB: Family Richness, Trichoptera Richness, % Coleoptera, % Diptera, IBE-IOC index, EPT / Chironomidae ratio. A test of the MISB in eleven sites indicated it was more related to land-use and water physico-chemical parameters than with altitude or stream width, being a useful tool for the monitoring and assessment of streams in the bioregion. PMID- 24212699 TI - Effects of some parameters in upscale culture of Haematococcus pluvialis Flotow. AB - Growth rate and medium parameters between two bench scale volumes (13-L and 250 L) were compared. Experiments were maintained batch mode and culture parameters were periodically measured during a 13-day period. Culture growth during the cultivation of algae Haematococcus pluvialis was determined qualitatively by cell counting, optical density, dry weight, ash content, amount of chlorophyll-a, total organic carbon content and by direct measuring of medium nutrients and some abiotic aspects. Vegetative cell growth was higher when cultured in 13-L with 1.33 x 10(5) cells.mL(-1) on the 12th day than when cultured in 250-L. Significant difference (p < 0.05) in the biology and water culture of H. pluvialis, with the exception of dry weight, ash, nitrite and ammonia, was reported between the volumes. Data obtained in current study for the upscale culture maintenance of H. pluvialis in laboratory conditions shows that it should be undertaken in a 13-L volume due to a greater time span of cells in a vegetative state, greater cell density, lipids and chlorophyll-a contents. Light was of paramount importance on the direct performance of H. pluvialis on the algal biological conditions. PMID- 24212700 TI - Length-weight relationships and biomass of the main microcrustacean species of two large tropical reservoirs in Brazil. AB - Length-weight equations were determined for the main microcrustacean species of Tres Marias and Furnas reservoirs (state of Minas Gerais, Brazil), and evaluated the fluctuations of their biomass. We examined the following species: Thermocyclops minutus, Bosminopsis deitersi, Bosmina hagmanni, Ceriodaphnia cornuta, and Moina minuta (Tres Marias Reservoir), and Notodiaptomus henseni, Daphnia ambigua, Ceriodaphnia silvestrii, Diaphanosoma spinulosum, D. fluviatile, and Bosmina freyi (Furnas Reservoir). Dry weight was obtained in a microbalance for each size class (Cladocera) or developmental stage (Copepoda). Microcrustacean mean biomass varied from 5.76 mg DW.m(-3) and 20.36 mg DW.m(-3) (Furnas Reservoir) and from 3.75 mg DW.m(-3) and 18.14 mg DW.m(-3) (Tres Marias Reservoir). Significant differences (p < 0.000) between seasons were registered with higher biomass during the rainy seasons. Thermocyclops minutus was the most important species in Tres Marias, whereas in Furnas, N. henseni contributed in equal proportion. In Furnas, the higher cladoceran biomass was explained by the contribution of larger-sized species, such as D. ambigua, C. silvestrii, D. spinulosum, and D. fluviatile. Even though both reservoirs are considered oligotrophic, there were significant differences in the estimated microcrustacean biomass, which reinforces the importance of this parameter for the description of the real contribution of each species in the community. PMID- 24212701 TI - Simultaneous pollinator occurence (Hymenoptera, Agaoninae) in a threatened species: Ficus mexiae Standley (Moraceae). AB - In Brazil, Ficus mexiae is classified as Vulnerable under IUCN criteria, and to date there is only one report on pollinator activity for this species. Is not unusual to find cases where more than one species of wasp simultaneously occurs on and pollinates the same fig. In this study we present evidence that two Pegoscapus wasp species contribute to the pollination of F. mexiae and relationship between pollinators maybe competitive. These results indicate that the F. mexiae population represent an important element in the complex dynamics of maintaining diversity in neotropical Ficus spp. PMID- 24212702 TI - The effect of salinity on osmoregulation and development of the juvenile fat snook, Centropomus parallelus (POEY). AB - Eurihaline fish support waters with different salt concentration. However, numerous studies have shown that salinity can affect fish development. Thus, the effect of salinity change from 20 to 5 and 35 on survival, weight, length, gill chloride cell ultrastructure and gill Na+, K+ ATPase activity was evaluated in Centropomus parallelus following short-term (6, 24 and 96 hours) and long-term exposure (30 and 60 days). Salinity did not affect C. parallelus survival, final weight and length. The quantity of chloride cells increased visibly at salinities of 5 and 35, with the cells exhibiting the typical features of uptake and secretory cells, respectively. Na+, K+ ATPase activity in the gill of the C. parallelus was significantly greater at a salinity of 5 than at a salinity of 20 or 35 after 96 hours, but not after 30 or 60 days. These results indicate that salinity change from high to low salt water induces gill chloride cell and Na+, K+ ATPase activity adaptations after short-term exposure. However, after long term exposure at salinity 5, gill Na+, K+ ATPase activity is no more necessary at high levels. The increase in salinity to 35 does not induce significant change in gills. Juveniles of C. parallelus may thus be capable of acclimating to salinities of 5 to 35 for 60 days without significant effects on development. PMID- 24212703 TI - Ethylene synthesis inhibition effects on oxidative stress and in vitro conservation of Lippia filifolia (Verbenaceae). AB - This study aimed to investigate the effects of ethylene biosynthesis inhibitors on oxidative metabolisms and the in vitro conservation of Lippia filifolia, using the lipid peroxidation index (TBARS), antioxidative enzymes and pigments as biomarkers. We found that EDTA, sodium thiosulfate (STS) and especially Co had protective effects on oxidative stress in tissues cultured in vitro, resulting in a delay of the senescence and the reduction of subcultures frequency, contributing to the germplasm conservation of this species. PMID- 24212704 TI - Uroguanylin induces electroencephalographic spikes in rats. AB - Uroguanylin (UGN) is an endogenous peptide that acts on membrane-bound guanylate cyclase receptors of intestinal and renal cells increasing cGMP production and regulating electrolyte and water epithelial transport. Recent research works demonstrate the expression of this peptide and its receptor in the central nervous system. The current work was undertaken in order to evaluate modifications of electroencephalographic spectra (EEG) in anesthetized Wistar rats, submitted to intracisternal infusion of uroguanylin (0.0125 nmoles/min or 0.04 nmoles/min). The current observations demonstrate that 0.0125 nmoles/min and 0.04 nmoles/min intracisternal infusion of UGN significantly enhances amplitude and frequency of sharp waves and evoked spikes (p = 0.03). No statistical significance was observed on absolute alpha and theta spectra amplitude. The present data suggest that UGN acts on bioelectrogenesis of cortical cells by inducing hypersynchronic firing of neurons. This effect is blocked by nedocromil, suggesting that UGN acts by increasing the activity of chloride channels. PMID- 24212705 TI - Seasonal variation of energy reserves and reproduction in neotropical free-tailed bats Molossus molossus (Chiroptera: Molossidae). AB - Seasonal variation is a key factor regulating energy metabolism and reproduction in several mammals, including bats. This study aimed to track seasonal changes in the energy reserves of the insectivorous bat Molossus molossus associated with its reproductive cycle. Adult males were collected during the four neotropical annual seasons in Vicosa - MG, Brazil. Blood and tissues were collected for metabolic analysis and testes were removed for histology and morphometry. Our results show that liver and breast muscle glycogen concentrations were significantly lower in winter. The adiposity index was significantly higher in the fall compared to winter and spring. Seminiferous tubules were greater in diameter in animals captured in fall and winter, indicating a higher investment in spermatic production during these seasons. The percentage of Leydig cells was higher in summer compared to fall and winter. We suggest that M. molossus presents a type of seasonal reproduction with two peaks of testicular activity: one in fall, with higher sperm production (spermatogenesis), and another in summer, with higher hormone production (steroidogenesis). The metabolic pattern may be associated with reproductive events, especially due to the highest fat storage observed in the fall, which coincides with the further development of the seminiferous tubules. PMID- 24212706 TI - Scale morphology of Prochilodus lineatus with emphasis on the scale epithelium. AB - The fish body is entirely covered by a thin, smooth and glandular epidermis, closely attached to the scales inserted on the dermis. The descriptive work on this tissue dates to twenty or thirty years ago, bears very little photographic record and does not focus on the scale epithelium, despite the fact that it is in direct contact with the environment. Thereupon, the present study characterizes the scale epithelium of Prochilodus lineatus, a robust species of fish. The observations show that the scale is completely covered by epithelium thicker on the proximal end of the scale, multilayered on the dorsal surface and undifferentiated on the ventral surface, and covered by mucous producing cells, mostly acid mucous. The scale is formed by plywood-like collagen matrix of collagen type III and supported by a network of elastic fibers on the ventral face. Differentiated cellular types are present, such as club cells, considered to be responsible for the release of alarm substances, which suggests possible use in environmental assessment as a non-invasive technique. PMID- 24212707 TI - Endoparasites infecting the semiaquatic coral snake Micrurus surinamensis (Squamata: Elapidae) in the southern Amazonian region, Mato Grosso state, Brazil. AB - A parasitological survey was conducted in specimens of the semiaquatic coral snake Micrurus surinamensis, a poorly known South American elapid. Four specimens collected at the southern Amazon region in the Brazilian state of Mato Grosso were analyzed for endoparasites. Three parasite species were recovered from the snake hosts: the pentastomid Sebekia oxycephala, the nematode Physaloptera sp. and the trematode Opisthogonimus lecithonotus. This represents new locality and host record for S. oxycephala and O. lecithonotus. PMID- 24212708 TI - Morphoanatomy of the flower of Syagrus inajai (SPRUCE) Becc. (Arecaceae- Arecoideae- Attaleinae), Amazon. AB - The occurrence of Syagrus inajai (Spruce) Becc., popularly known as pupunha palm, among other names, has been registered in the Guianas and in the North of Brazil in areas of terra firme (non-flooding) and gallery forests. In order to characterize the inflorescence and further knowledge of this family, a morphoanatomical study was carried out of the palm S. inajai in a green area of the Campus of the Federal University of Amazonas--UFAM, Manaus, Amazonas. The inflorescences are branched to one order, pedunculate, and interfoliar, measuring 62-82 cm in length, with woody bracts with longitudinal grooves on the external surface, and flowers in triads. The number of flowers to each inflorescence varies from 5,904 to 17,316 for staminate flowers, and from 180 to 3,528 for pistillate flowers. Staminate flowers with six anthers and one vascular bundle each; three-lobed pistillodium, vascularized pistillodium. Its pistillate flowers have six staminodia joined to form a circle, syncarpic, tricarpellary, trilocular gynoecium, one ovule to each locule, synascidiate in the ovary, and plicated above. Tripartite stigma, apical and sessile, with epidermis composed of elongated papillary cells, pattern of epidermis that is maintained throughout the stylar canal. Bitegmented, anatrope, pachychalazal ovule. PMID- 24212709 TI - Morphological and morphometric studies of the antennal sensilla from two populations of Atta robusta (Borgmeier 1939) (Hymenoptera: Formicidae). AB - The ant Atta robusta is endemic to the "restinga" ecosystems where it has an important role in the dynamics of seed dispersal. Despite its importance, A. robusta is considered a threatened species. In this study we analyzed the antennal sensory organs of two different populations of A. robusta (from the cities of Sao Mateus and Marica in in Espirito Santo and Rio de Janeiro States, respectively) using a scanning electron microscope (SEM). SEM revealed different types of sensilla in the A. robusta antennae, i.e., curved and straight trichoid, basiconic, ampullacea and coeloconic, which were highly abundant found in the distal flagellomeres (F) compared with other antenna regions. There were differences in samples collected from two locations in terms of the sensilla number and length. The average numbers of straight and curved trichoid sensillae numbers were different in F9 and F8, respectively, while the average length of the curved trichoid sensilla was only different in F9. These variations in sensory organs between two populations of A. robusta may indicate an adaptation of this species to different environmental conditions. The number of straight trichoid sensilla was only significantly different in F9. PMID- 24212710 TI - Synanthropic characteristics of the cattle egret Bubulcus ibis (Linnaeus, 1758) in the Brazilian semiarid. PMID- 24212711 TI - First records of melanistic Euglossa (Hymenoptera: Apidae): evolutionary implications. PMID- 24212712 TI - Rhinonyssidae (Acari: Gamasida) in Ardeidae (Aves: Pelicaniformes) in Brazil. PMID- 24212713 TI - Report of Carettacola stunkardi (Martin & Bamberger, 1952) Dailey, Fast & Balazs, 1991 (Digenea: Spirorchiidae) infecting green turtle Chelonia mydas Linnaeus, 1758 (Testudines, Cheloniidae) in Brazil. PMID- 24212714 TI - Trigona pallens (Fabricius, 1798)(Hymenoptera: Apidae) strongly attracted to vanillin in northeastern Peru. PMID- 24212715 TI - Sound production in four species of the Loricariidae family. PMID- 24212716 TI - Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns. AB - Due to the heterogeneous nature of breast cancer and the widespread use of single gene studies, there is limited knowledge of multi-gene, locus-specific DNA methylation patterns in relation to molecular subtype and clinical features. We, therefore, quantified DNA methylation of 70 candidate gene loci in 140 breast tumors and matched normal tissues and determined associations with gene expression and tumor subtype. Using Sequenom's EpiTYPER platform, approximately 1,200 CpGs were interrogated and revealed six DNA methylation patterns in breast tumors relative to matched normal tissue. Differential methylation of several gene loci was observed within all molecular subtypes, while other patterns were subtype-dependent. Methylation of numerous gene loci was inversely correlated with gene expression, and in some cases, this correlation was only observed within specific breast tumor subtypes. Our findings were validated on a larger set of tumors and matched adjacent normal tissue from The Cancer Genome Atlas dataset, which utilized methylation data derived from both Illumina Infinium 27 and 450 k arrays. These findings highlight the need to control for subtype when interpreting DNA methylation results, and the importance of interrogating multiple CpGs across varied gene regions. PMID- 24212718 TI - The proarrhythmic effect of hypoglycemia: evidence for increased risk from ischemia and bradycardia. AB - Hypoglycemia increases the risk for both overall and sudden death. At a cellular level, hypoglycemia causes alterations in the physiology of myocardial tissue that are identical to proarrhythmic medications. Reduced serum glucose blocks the repolarizing K(+) channel HERG, which leads to action potential and QT prolongation and is uniformly associated with risk for torsades de pointes ventricular tachycardia. The sympathetic response induced by hypoglycemia also increases the risk of arrhythmias from Ca(2+) overload, which occur with sympathomimetic medications and excessive beta adrenergic stimulation. Thus, hypoglycemia can be considered a proarrhythmic event. This review focuses on emerging evidence for two other important changes induced by hypoglycemia that promote arrhythmias: ischemia and bradycardia. Studies of patients with "insulin shock" therapy from the early twentieth century and other more recent data strongly suggest that hypoglycemia can cause ischemia of myocardial tissue, both in association with coronary artery obstructions and by cellular mechanisms. Ischemia induces multiple proarrhythmic responses. Since ischemia itself reduces the possibility of using energy substrates other than glucose, hypoglycemia may generate positive feedback for electrophyisologic destabilization. Recent studies also show that hypoglycemia can cause bradycardia and heart block. Bradycardia is known to cause action potential prolongation and potentiate the development of torsades de pointes, particularly with low-serum K(+) which can be induced by hypoglycemic episodes. Thus, hypoglycemia-induced bradycardia may also create a dynamic, positive feedback for the development of arrhythmias and sudden death. These studies further support the hypothesis that hypoglycemia is a proarrhythmic event. PMID- 24212717 TI - DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells. AB - TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple-negative, human MDA-MB-231 breast cancer cells stably expressing control, or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID- 24212719 TI - Association between extraversion personality and abnormal glucose regulation in young Korean women. AB - Depression and psychological distress are known to be associated with diabetes development as well as the disease progression including glycemic control and chronic complication, but relationship of personality with diabetes is controversial. We examined whether personality trait and the presence of abnormal glucose regulation (AGR; diabetes and pre-diabetes) are associated in young women. A total of 1,617 young women aged 19-39 years without previously diagnosed diabetes were participated voluntarily. Personality trait was assessed by self reported questionnaire using the five-factor model (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) consisting of five point scale ranging from 'strongly disagreeable' to 'strongly agreeable.' Glucose tolerance status was assessed by standard 75-g oral glucose tolerance test. One hundred and eleven women were newly diagnosed with AGR (6.9 %). Among five factors, only extraversion trait was significantly associated with AGR. Multiple linear regression analysis showed significant negative association between extraversion trait and 2-h post-load glucose after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL cholesterol and family history of diabetes (beta = -0.16, P = 0.026). Multiple logistic regression showed extraversion trait having a significant association with the presence of AGR after adjustment for the same covariates (OR 0.97, 95 % CI 0.95-0.99, P = 0.011). The frequency of AGR was significantly increased according to the decrease in extraversion score (P for trend with exact test = 0.047). In conclusion, extraversion may be an important personality trait having a beneficial effect on decreasing the risk of AGR. PMID- 24212720 TI - Prognostic significance of the highest peripancreatic lymph node in biliary tract adenocarcinoma. AB - BACKGROUND: Patients with biliary tract adenocarcinoma with nodal involvement have a poor prognosis. There is currently no standardized method for intraoperative lymph node assessment. The current study aimed to determine the prognostic significance of the highest peripancreatic lymph node (HPLN) in biliary tract malignancy. METHODS: This was a retrospective study of patients undergoing potential curative resection of biliary tract adenocarcinoma from January 1995 through December 2010 who prospectively had intraoperative sampling of the HPLN. The median follow-up was 72.8 months. The primary end points were recurrence-free survival (RFS) and disease-specific survival (DSS). RESULTS: The rate of HPLN positivity in 110 patients undergoing exploration for potential curative resection was 30 % and did not vary with histologic subtype (gallbladder vs. cholangiocarcinoma). Eighty-five patients underwent complete gross resection. In this subset, median RFS and DSS were 34.3 months (95 % confidence interval [CI] 23.6-not reached [NR]) and 62.4 months (95 % CI 40.8-NR) for HPLN-negative patients, and 9.6 months (95 % CI 4.76-NR) and 20.5 months (95 % CI 7.4-NR) for HPLN-positive patients (p < 0.01), respectively. Median DSS was 14.6 months (95 % CI 9.6-25.4) for patients with unresectable disease. On multivariate analysis, HPLN status was an independent predictor of RFS (hazard ratio 3.73, 95 % CI 1.86 7.45; p < 0.01) and DSS (hazard ratio 3.98, 95 % CI 1.89-8.38; p < 0.01). CONCLUSIONS: HPLN status is prognostic of RFS and DSS in biliary tract adenocarcinoma. Intraoperative nodal staging by HPLN sampling warrants further investigation in a prospective trial. PMID- 24212722 TI - Assessment of short-term clinical outcomes following salvage esophagectomy for the treatment of esophageal malignancy: systematic review and pooled analysis. AB - BACKGROUND: Combined chemoradiotherapy is increasingly being used as definitive treatment for locoregional esophageal malignancy. Patients with residual or recurrent localized cancer are often selectively considered for salvage esophagectomy (SALV). The aim of this pooled analysis was to compare short-term clinical outcomes from SALV following definitive chemoradiotherapy with those from planned esophagectomy following neoadjuvant chemoradiotherapy (NCRS). METHODS: MEDLINE, EMBASE, Cochrane, trial registries, conference proceedings and reference lists were searched for relevant comparative studies. Primary outcome measures were in-hospital mortality, anastomotic leak and pulmonary complications. Secondary outcomes were length of hospital stay, negative (R0) resection margin, and estimated blood loss. RESULTS: Eight studies comprising 954 patients; 242 (SALV) and 712 (NCRS) were included. SALV was associated with a significantly increased incidence of post-operative mortality (9.50 vs. 4.07 %; pooled odds ratio [POR] = 3.02; p < 0.001), anastomotic leak (23.97 vs. 14.47 %; POR = 1.99; p = 0.005), pulmonary complications (29.75 vs. 16.99 %; POR = 2.12; p < 0.001), and an increased length of hospital stay (weighted mean difference = 8.29 days; 95 % CI 7.08-9.5; p < 0.001). There were no significant differences between the groups in the incidence of negative resection margins or estimated blood loss. CONCLUSIONS: SALV has poorer short-term outcomes when compared with planned esophagectomy following neoadjuvant chemoradiotherapy. Patients and multidisciplinary tumor boards should be made aware of these differences in outcomes and SALV should be reserved for practice in high-volume institutions. PMID- 24212721 TI - MET gene copy number gain is an independent poor prognostic marker in Korean stage I lung adenocarcinomas. AB - BACKGROUND: MET gene copy number gain (CNG) and protein overexpression have been reported in lung cancer, but the clinical implications in early stage adenocarcinoma remain unclear. METHODS: We investigated MET gene copy number and protein expression in 141 cases of surgically resected stage I pulmonary adenocarcinoma. MET gene CNG was determined by silver in situ hybridization, and MET protein expression was assessed by immunohistochemistry. The correlation between MET gene CNG/protein expression and clinicopathologic parameters and prognostic significance was analyzed. RESULTS: MET gene CNG was found in 24.1% (34 of 141) of the cases and was associated with larger tumor size, pleural invasion, and lymphatic vessel invasion. MET gene CNG was inversely correlated with the presence of lepidic subtype (r = -0.17, p = 0.045) and was not associated with EGFR, KRAS mutation, or ALK gene rearrangement. In addition, MET gene CNG was significantly associated with shorter disease-free survival (DFS) (49 vs. 75 months; p < 0.001) and shorter overall survival (OS) (65 vs. 78 months; p = 0.01). Multivariate analysis confirmed that MET gene CNG was significantly associated with poorer DFS [p < 0.001; hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.2-13.9] but was not significantly associated with OS. MET overexpression was observed in 71.3% of cases (97 of 136), but it was not correlated with gene CNG. CONCLUSIONS: MET gene CNG is an independent poor prognostic factor in patients with stage I lung adenocarcinoma. It is associated with aggressive pathologic features and is inversely correlated with the presence of lepidic subtype. PMID- 24212723 TI - A selective fluorescence turn-on sensor for trace vapor detection of hydrogen peroxide. AB - A fluorescence turn-on sensor molecule (C6NIB) has been synthesized and fabricated into a porous matrix to enable trace vapor detection of hydrogen peroxide. The detection limit was projected to be below 5 ppb. PMID- 24212725 TI - Effective and selective sorption of iodide by thin film of multilayered MnO(2) intercalated with cationic surfactants. AB - We have fabricated a thin film of multilayered MnO2 whose interlayer is occupied with hexadecylpyridinium (HDPy) cations, using a simple anodic approach. The resulting film can effectively sorb iodide anions from aqueous solutions, even in the presence of NaCl or Na2SO4. The maximum sorption capacity was estimated to be 256 mg/g-MnO2, whereas a layered MnO2 film intercalated with K(+) ions showed no significant sorption. The layered structure of the HDPy/MnO2 composite remained unchanged after a sorption experiment. This indicates the incorporation of I(-) ions between MnO2 layers due to their specific affinity toward HDPy. PMID- 24212724 TI - Antitoxin MqsA represses curli formation through the master biofilm regulator CsgD. AB - MqsA, the antitoxin of the MqsR/MqsA toxin/antitoxin (TA) system, is a global regulator that reduces expression of several stress response genes (e.g., mqsRA, cspD, and rpoS) by binding to the promoter palindromic motif [5'-AACCT (N)3 AGGTT 3']. We identified a similar mqsRA-like palindrome [5'-AACCT TA AGGTT-3'] 78 bp upstream of the transcription initiation site in the csgD promoter (p-csgD). CsgD is a master regulator for biofilm formation via its control of curli and cellulose production. We show here that MqsA binds to this palindrome in p-csgD to repress csgD transcription. As expected, p-csgD repression by MqsA resulted in reduced transcription from CsgD-regulated curli genes csgA and csgB (encoding the major and minor curlin subunits, respectively). Curli production was reduced in colonies and in planktonic cells upon MqsA production. Hence, MqsA directly represses p-csgD, and thereby influences curli formation. This demonstrates that TA systems can impact overall cell physiology by fine-tuning cellular stress responses. PMID- 24212726 TI - Colorimetric determination of glucosamine and glucose based on the formation of blue molybdosilicate anion and its application to the assay of saccharifying enzyme. AB - A simple and convenient method of reducing monosaccharide assay is proposed. A Si(IV)-Mo(VI) solution (pH 4.9) was yellow due to the formation of the 11- and/or 12-molybdosilicate(VI) anions. By the addition of a reducing saccharide, glucosamine, the mixture turned to blue gradually, indicating that the Mo(VI) species was reduced by the saccharide to form a blue molybdosilicate anion. The molybdenum blue formation occurred more quickly when a water-miscible organic solvent, dimethyl sulfoxide, was added to the Si(IV)-Mo(VI) solution. Thus, 0.01% level glucosamine can be determined colorimetrically with microtiter plate. Oligochitosan would not interfere with the determination of the glucosamine at the same concentration. Also, a remarkable blue color development of the Si(VI) Mo(VI) solution was observed by the addition of glucose. On the other hand, maltose, cellobiose, and water-soluble starch at the same concentration level gave no significant coloration of the reaction mixture. Thus, the present monosaccharide assay can be applied advantageously to evaluate the saccharification to produce glucosamine and glucose. PMID- 24212727 TI - Distribution of the elements in cotyledon, embryonic axis, and testa of peanut seeds obtained by ICP-MS with microwave acid digestion. AB - Eighteen elements in the cotyledon, the embryonic axis, and the testa of peanut seeds were determined by inductively coupled plasma mass spectrometry (ICP-MS) after microwave acid digestion, while the gravimetric standard addition with internal standard was applied for the calibration of the elemental concentrations. The detection limit and the procedure blank value for each element were low enough to ensure the precise analysis of the elements, with a relative expanded uncertainty of less than 5%. The concentrations of the elements in peanut seed samples covered 6 orders of magnitude from approximately 0.01 mg kg(-1) of Co to approximately 7000 mg kg(-1) of K. The correlation coefficient factor was around 0.98 for the elemental concentrations in peanut seeds grown in Japan and those grown in China, indicating a good correlation. Most of the elements distributed in the cotyledon in large amounts because of the cotyledon's relatively high mass fraction. By contrast, Na, Ca, Fe, Co, Ni, Cu, Ga, Sr, Cd, and Ba were apparently enriched in the testa and the relative enrichment factor (REF) values of the elements were over 4. The relative enrichment of Mo, Fe, Zn and other elements was observed in the embryonic axis samples with REF values over 2. The relative enrichment of Cd in the testa of peanut seed indicates that about 15 to 25% of the Cd intake through peanut seeds could be effectively lowered by removal of the testa (roughly 2.5 to 3.5% of the peanut seed). PMID- 24212728 TI - Laser desorption ionization mass spectrometry of bioactive substances by using 2,4,6-trihydroxyacetophenone on cation-substituted zeolite. AB - By using 2,4,6-trihydroxyacetophenone adsorbed to cation-substituted zeolite, laser desorption/ionization mass spectrometry for six kinds of bioactive substances was carried out. The compounds, which were usually difficult to observe by conventional matrix-assisted laser desorption/ionization mass spectrometry, were ionized by cation adduction from the zeolite surface. PMID- 24212729 TI - Spectrophotometric determination of hydrogen peroxide, glucose, uric acid, and cholesterol using peroxidase-like activity of an Fe(III) complex of thiacalix[4]arenetetrasulfonate attached to an anion-exchanger. AB - An iron(III) complex of thiacalix[4]arenetetrasulfonate attached to an anion exchanger (Fe(3+)-TCASA-500) showed high peroxidase-like catalytic activity at pH 5 - 8 for the formation of quinoid dye, following the color reaction between 3 methyl-2-benzothiazolinone hydrazone (MBTH) and N-ethyl-N-(3-sulfopropyl)aniline (ALPS) in the presence of H2O2. This catalytic activity of Fe(3+)-TCASA-500 for the MBTH-ALPS system was applied for the spectrophotometric determination of H2O2, glucose, uric acid, and cholesterol. The calibration curves were linear in the concentration range from 1.0 to 15 MUg of H2O2 in a 1.0-mL sample solution, and from 5.0 to 60 MUg of glucose, 2.0 to 30 MUg of uric acid, and 11.6 to 116 MUg of cholesterol in a 0.5-mL sample solution. The apparent molar absorptivity of H2O2 was determined as 2.31 * 10(4) L mol(-1) cm(-1), which was about 70% of that by peroxidase under the same conditions. The determination method using Fe(3+)-TCASA-500 was applied for the determination of glucose and uric acid in both control sera I and II. PMID- 24212730 TI - Microwave-assisted acid hydrolysis of konjac products for determining the konjac powder content. AB - The complete hydrolysis of konjac glucomannan (KGM) with an acid or enzyme generally takes a long time. To accelerate KGM hydrolysis without diminishing the conventional quality, a diluted acid hydrolysis of KGM with sulfuric acid was conducted using a microwave digestion system. The optimum conditions of microwave assisted acid hydrolysis for KGM were: 10 mL of 0.25 M sulfuric acid, hydrolysis temperature of 135 degrees C (microwave power of 600 W), and total microwave irradiation time of 45 min. The yields of the component sugars, mannose and glucose, from two konjac powders were similar to those by conventional acid hydrolysis with 1 M sulfuric acid in a boiling water bath for 5 h. Furthermore, a pretest for microwave-assisted acid hydrolysis using mixtures of konjac powder and starch at different ratios proved that their konjac content can be calculated by determining the mannose generated by the new rapid hydrolysis method, if the raw materials are provided. PMID- 24212731 TI - On-line flow-injection liquid-phase microextraction and spectrophotometric determination of traces of copper(II) with trithia-9-crown-3 as complexing agent. AB - A novel on-line flow-injection liquid-phase microextraction (FI-LPME) and spectrophotometric determination of the Cu(2+) ion using trithia-9-crown-3 (TT9C3) as a sensitive and selective charge transfer complexing agent was developed. After phase segmentation by pulsating motions of a peristaltic pump, the phase separation takes place by the aid of gravitation forces. The optimum values of the pH (= 5 of phosphate buffer) and ionic strength (5 mM Na2SO4) of the solution, amount of ligand (2.0 * 10(-3) mol L(-1)), nature of the counter ion (10 mM SDS), volume of the organic solvent (150 MUL), coil length (3 m) and extraction time (2 min) for an efficient extraction were determined. The calibration curve was found to be linear over a concentration range of 0.008 - 4.2 MUg mL(-1) (R(2) = 0.9985) with a limit of detection of 0.37 ng mL(-1). The enrichment factor and relative standard deviation (n = 7) were 16 and 5.7%, respectively. Finally, the proposed method was applied to the determination of copper(II) as an impurity in the several commercial metallic salts. PMID- 24212733 TI - Analysis of fast and slow acid dissociation equilibria of 3',3",5',5" tetrabromophenolphthalein and determination of its equilibrium constants by capillary zone electrophoresis. AB - Acid dissociation constants of 3',3",5',5"-tetrabrompohenolphthalein (TBPP) were determined in an aqueous solution by capillary zone electrophoresis at an ionic strength of 0.01 mol/L. Two steps of the fast acid-dissociation equilibria including precipitable species of H2TBPP were analyzed at a weakly acidic pH region by using the change in effective electrophoretic mobility of TBPP with the pH of the separation buffer. On the other hand, an acid-dissociation reaction of TBPP at an alkaline pH region was reversible, but very slow to reach its equilibrium; the two TBPP species concerned with the equilibrium were detected as distinct signals in the electropherograms. After reaching its equilibrium, the acid-dissociation constant was determined with the signal height corresponding to its dianion form. Thus, three steps of the acid dissociation constants of TBPP were determined in an aqueous solution as pKa1 = 5.29 +/- 0.06, pKa2 = 6.35 +/- 0.02, and pKa3 = 11.03 +/- 0.04. PMID- 24212732 TI - Determination of thiram and aminocarb pesticides in natural water samples using flow injection with tris(2,2'-bipyridyl)ruthenium(II)-diperiodatoargentate(III) chemiluminescence detection. AB - A simple and sensitive flow-injection (FI) method is reported for the determination of thiram and aminocarb pesticides in natural water samples based on the strong enhancing effects of these pesticides on the tris(2,2' bipyridyl)ruthenium(II)-diperiodatoargentate(III) (Ru(bipy)3(2+)-DPA) chemiluminescence (CL) system. Under the optimum experimental conditions, the CL intensity was linear over the range of 1.0 - 1000 and 1.0 - 10000 ng mL(-1) (R(2) = 0.9998 (n = 7) and 0.9994 (n = 11)) for thiram and aminocarb, respectively, with relative standard deviations (RSDs; n = 3) in the range 1.0 - 2.6%. The limits of detection (S/N = 3) were 0.1 ng mL(-1) for both pesticides with injection throughputs of 150 h(-1). The key chemical and physical variables (reagent concentrations, flow rates, sample volume, PMT voltage) were optimized and potential interferences investigated. The method was successfully applied to natural water samples and the results obtained were not significantly different (95% confidence interval) from results obtained by the previously reported FI-CL and HPLC methods. Thiram could be determined in the presence of aminocarb using Triton X-100. The possible CL reaction mechanism is also discussed briefly. PMID- 24212734 TI - Investigation on the conformation change of hemoglobin immobilized on MPA modified electrode by electrochemical method. AB - The conformation change of bovine hemoglobin (Hb) during the unfolding process induced by urea and acid was investigated by an electrochemical method. Hb unfolding induced by urea of different concentrations was realized by bonding Hb onto a 3-mercaptopropionic acid (MPA) modified gold electrode. The difference in unfolding percentage showed that the Hb unfolding induced by urea was a two-step, three-state transition process, while the unfolding induced by acid was a two state transition process. The results obtained by the electrochemical method coincided closely with those obtained by UV-vis spectroscopy and fluorescence spectroscopy. Some thermodynamic parameters during the conformational change were also calculated to study the intermediate state during the Hb unfolding process. The present work may lead to an easy and effective way to study metalloproteins unfolding, and holds great promise for the design of novel sensitive biosensors. PMID- 24212735 TI - Determination of Li(+) diffusion coefficients in the LixV2O5 (x = 0 - 1) nanocrystals of composite film cathodes. AB - The Li(+) ion diffusion coefficients (DLi+) in V2O5 (2.12 * 10(-12) cm(2) s(-1)) and in the intermediate alpha-, epsilon-, and delta-LixV2O5 phases (1.6 * 10( 14), 8.0 * 10(-15), and 8.5 * 10(-15) cm(2) s(-1), respectively), reversibly formed during charging/discharging processes of the crystalline-V2O5 and PEDOT (poly-3,4-ethylenedioxythiophene) composite-film electrode, are precisely determined by the galvanostatic intermittent titration technique. The specific surface area of the composite film is estimated to be 13.600 m(2) g(-1), where the external surface area and the nanopore area are 10.704 and 2.896 m(2) g(-1), respectively. The V2O5 crystals are coated and interconnected by a conductive polymer network in the composite film, thereby improving the electrode characteristics. V2O5 and PEDOT composite-film cathodes showed high specific capacities (290 mA h g(-1) at a 1 C rate), excellent rate capabilities (178 mA h g(-1) at a 10 C rate), and superior cycling stabilities (ca. 15% degradation after 500 consecutive cycles). PMID- 24212736 TI - Temperature distribution in a solid state NMR sample rotor during MAS experiments. AB - We investigated temperature distribution in a solid state nuclear magnetic resonance (NMR) sample rotor under magic angle spinning (MAS) experiments by analyzing the (207)Pb chemical shift of solid lead nitrate (Pb(NO3)2). The analysis corrected a mismatch of the temperature dependence of (1)H spin-lattice relaxation time (T1(H)) obtained from different sample positions in the rotor. We prepared three rotors that consisted of Pb(NO3)2 partitioned into the three different parts with Teflon spacers, and measured the temperature distribution related to the placement using the prepared three rotors. The obtained temperature distribution showed a large gradient in the sample rotor. The temperature distribution was related to the placement in the rotor and successfully visualized. Finally, the divergent temperature dependence of T1(H) obtained at different placement positions in the sample rotor was successfully corrected to accurate temperature dependence. PMID- 24212737 TI - Colorimetric determination of pyrophosphate anion and its application to adenylation enzyme assay. AB - A colorimetric pyrophosphate assay based on the formation and reduction of the 18 molybdopyrophosphate ([(P2O7)Mo18O54](4-)) anion in an acetonitrile-water mixed solvent was modified and improved. The [(P2O7)Mo18O54](4-) anion is precipitated from the acetonitrile-water solution containing MoO4(2-) and HCl, and is re dissolved in neat acetonitrile or propylene carbonate. This separation process decreases the interference by ATP, and prevents a yellow coloration of the reducing agent, ascorbic acid, due to excess Mo(VI) species. In the organic solvent, the [(P2O7)Mo18O54](4-) anion is reduced to a more intense blue molybdopyrophosphate species. The application of the colorimetry to the assay of adenylation enzymes is also described in this note. PMID- 24212738 TI - Dynamic coating capillary electrophoresis for separation of humic acid using mixture solution of non-ionic polymers both as coating agent and separation medium. AB - A simple, rapid, and precise dynamic coating capillary electrophoretic separation method for water-soluble humic substances is proposed. An aqueous solution containing hydroxyethyl cellulose (HEC), polyethylene glycol (PEG), and pH buffer component was employed for both the dynamic coating agent and the separation medium. The procedure for the coating of the capillary inner wall was simply filling the buffered polymer mixture solution into the capillary that had been treated with 1 M aqueous HCl solution. The solution for the capillary coating was directly used as the electrophoretic buffer solution for CE separation. Excellent performance for the separation of humic acid was obtained using the solution containing 0.5% (w/v) HEC, 1.0% (w/v) PEG 10000, and 0.1% (w/v) PEG 8000000. Excellent reproducibility and durability were obtained even at slightly alkaline conditions at pH levels above 8. The separation of 0.1 - 2 kbp of DNA ladder by the proposed method showed was also achieved. PMID- 24212739 TI - Insolubilization of cadmium in paddy field using atomized iron powder and extracting reagent. AB - The insolubilization of cadmium in the soil of a naturally cadmium-contaminated paddy field was studied using an atomized iron powder and an extracting reagent. Cadmium in the soil was extracted into the water phase by calcium chloride. The extracted cadmium was deposited on the iron powder. The deposition of cadmium was significantly influenced by calcium chloride, since the surface area of the iron powder increased with the increasing calcium chloride concentration. We discuss the potential of the technique and the insolubilization mechanism. PMID- 24212740 TI - Potential of Presep((r)) PolyChelate as a chelating resin: comparative study with some aminocarboxylic acid-type resins. AB - The potential of Presep((r)) PolyChelate as a chelating resin was studied in detail. The chelating resin with extraction capacity for Cu of 0.30 mmol L(-1) could quantitatively extract Cd, Co, Cu, Fe, Mo, Ni, Pb, V, and Zn at pH 4 or 5.5; however, only very scant amounts of Na, K, Mg, and Ca were captured at pH levels below 7. The quantitative extraction could be achieved in 100 - 1000 mL of artificial seawater and at a flow rate of 3 - 30 mL min(-1). The performance of Presep((r)) PolyChelate was compared to the other aminocarboxylic acid-type chelating resins, including Nobias Chelate-PA1, Chelex 100, Muromac B-1, Lewatit TP 207, and NTA Superflow, under the same conditions. The solid-phase extraction of the nine elements in the certified reference material (ES-L-1, ground water) and a commercially available table salt was also demonstrated. PMID- 24212742 TI - Floral and growth responses in Chenopodium rubrum L. to an extract from flowering Nicotiana tabacum L. AB - Flowering of Chenopodium rubrum seedling plants was obtained in continuous light after application of fractions of a partially purified extract from leaves of flowering Maryland Mammoth tobacco (Nicotiana tabacum). The stage of flowal differentiation was dependent on the age of the Chenopodium plants used for the bioassay. Apices of plants treated with the extract at the age of four or seven days showed an advanced branching of the meristem or the beginning of formation of a terminal flower; treatment with the extract of plants 12 d old resulted in rapid formation of flower buds in all assay plants. Non-treated control plants kept in continuous light remained fully vegetative. The effects of the extract on flowering were associated with pronounced growth effects. Floral differentiation was preceeded by elongation of the shoot apex. Extension of all axial organs occurred, while growth of leaves, including leaf primordia, was inhibited. The pattern of growth after application of the flower-inducing substance(s) did not resemble the effects of the known phytohormones, but showed some similarities to growth changes resulting from photoperiodic induction of flowering. PMID- 24212743 TI - Phytochrome structure: Peptide fragments from the amino-terminal domain involved in protein-chromophore interactions. AB - We have undertaken a study of the structure of the amino-terminal domain of the phytochrome polypeptide purified from Avena sativa L. Amino-acid sequencing was used to indentify arginine 52 as the precise location of a conformation-specific cleavage of phytochrome by subtilisin. The location of the epitopes for a class of monoclonal antibodies designated type 2 has been shown to be located between approx. 10 and 20 kilodaltons (kDa) from the amino terminus. These two new spatial markers, in addition to the chromophore and another epitope recognized by type 1 monoclonal antibodies and located within 6 kDa from the amino terminus, have been used to map the locations of several new protease-accessible sites along the polypeptide. After extensive digestion of phytochrome with subtilisin, a stable spectrally-active group of peptides remains. Within this group is a 16 kDa chromopeptide which, either alone or as part of an assemblage of peptides, elutes from a size-exclusion column under nondenaturing conditions at a volume consistent with a molecular mass of 35-40 kDa. This group of peptides has an absorbance spectrum similar to the red-absorbing form of phytochrome (Pr) and is red/far-red photoreversible between this and a photobleached form. These data indicate that this group of peptides still retains the principal structural requisites for Pr-chromophore-protein interactions and for photoreversibility, but not for Pfr (far-red-absorbing phytochrome)-chromophore-protein interactions. It is uncertain if these structural requisites reside exclusively on the 16-kDa chromopeptide or result from an assemblage of these peptides. However, we have excluded any role for an adjacent 14-kDa fragment (approximately residues 50 to 200) in the observed spectral properties since it can be selectively removed without any effect on the photoreversibility. PMID- 24212744 TI - Chromatographic and immunological evidence that chloroplastic and cytosolic pea (Pisum sativum L.) NADP-isocitrate dehydrogenases are distinct isoenzymes. AB - Two NADP-isocitrate dehydrogenase isoenzymes designated as NADP-IDH1 and NADP IDH2 (EC 1.1.1.42) were identified in pea (Pisum sativum) leaf extracts by diethylaminoethylcellulose chromatography. The predominant form was found to be NADP-IDH1 while NADP-IDH2 represented only about 4% of the total leaf enzyme activity. These enzymes share few common epitopes as NADP-IDH2 was poorly recognized by the specific polyclonal antibodies raised against NADP-IDH1, and as a consequence NADP-IDH2 does not result from a post-translational modification of NADP-IDH1. Subcellular fractionation and isolation of chloroplasts through a Percoll gradient, followed by the identification of the associated enzymes, showed that NADP-IDH1 is restricted to the cytosol and NADP-IDH2 to the chloroplasts. Compared with the cytosolic isoenzyme, NADP-IDH2 was more thermolabile and exhibited a lower optimum pH. The data reported in this paper constitute the first report that the chloroplastic NADP-IDH and the cytosolic NADP-IDH are two distinct isoenzymes. The possible functions of the two isoenzymes are discussed. PMID- 24212745 TI - Gas-exchange of ears of cereals in response to carbon dioxide and light : II. Occurrence of a C3-C 4 intermediate type of photosynthesis. AB - Data for the maximum carboxylation velocity of ribulose-1,5-biosphosphate carboxylase, Vm, and the maximum rate of whole-chain electron transport, Jm, were calculated according to a photosynthesis model from the CO2 response and the light response of CO2 uptake measured on ears of wheat (Triticum aestivum L. cv. Arkas), oat (Avena sativa L. cv. Lorenz), and barley (Hordeum vulgare L. cv. Aramir). The ratio Jm/Vm is lower in glumes of oat and awns of barley than it is in the bracts of wheat and in the lemmas and paleae of oat and barley. Light microscopy studies revealed, in glumes and lemmas of wheat and in the lemmas of oat and barley, a second type of photosynthesizing cell which, in analogy to the Kranz anatomy of C4 plants, can be designated as a bundle-sheath cell. In wheat ears, the CO2-compensation point (in the absence of dissimilative respiration) is between those that are typical for C3 and C4 plants.A model of the CO2 uptake in C3-C4 intermediate plants proposed by Peisker (1986, Plant Cell Environ. 9, 627 635) is applied to recalculate the initial slopes of the A(p(c)) curves (net photosynthesis rate versus intercellular partial pressure of CO2) under the assumptions that the Jm/Vm ratio for all organs investigated equals the value found in glumes of oat and awns of barley, and that ribulose-1,5-bisphosphate carboxylase is redistributed from mesophyll to bundle-sheath cells. The results closely match the measured values. As a consequence, all bracts of wheat ears and the inner bracts of oat and barley ears are likely to represent a C3-C4 intermediate type, while glumes of oat and awns of barley represent the C3 type. PMID- 24212746 TI - Immunocytochemical localization of patatin, the major glycoprotein in potato (Solanum tuberosum L.) tubers. AB - Patatin is a family of glycoproteins with an apparent molecular weight of 40 kDa. The protein is synthesized as a pre-protein with a hydrophobic signal sequence of 23 amino acids. Using different immunocytochemical methods we determined the tissue-specific as well as subcellular localization of the patatin protein. Since antibodies raised against patatin showed crossreactivity with glycans of other glycoproteins, antibodies specific for the protein portion of the glycoprotein were purified. Using these antibodies for electron-microscopical immunocytochemistry, the protein was found to be localized mainly in the vacuoles of both tubers and leaves of potatoes (Solanum tuberosum L.) induced for patatin expression. Neither cell walls nor the intercellular space contained detectable levels of patatin protein. Concerning the tissue specificity, patatin was mainly found in parenchyma cells of potato tubers. The same distribution was observed for the esterase activity in potato tubers. PMID- 24212747 TI - Cold-induced mRNAs accumulate with different kinetics in barley coleoptiles. AB - The effect of cold treatment on gene expression in two different barley (Hordeum vulgare L.) cultivars has been studied. Cold stress induced a set of new mRNAs as determined by in-vitro translation of coleoptile RNA obtained from control and stressed seedlings. These mRNAs accumulated with different kinetics, and the cold induced proteins could be grouped into five categories. The first category (a) is represented by a single protein with Mr of 75 kDa that reaches its highest level of expression after 6 h at 5 degrees C. This polypeptide readily accumulates in the plant tissues and it can be detected when proteins separated by two dimensional electrophoresis are stained with silver nitrate. The other polypeptides appear later during the 1- to 4-d stress period (protein groups b and c), increase (group d), or decrease during the period of treatment (group e). Only minor differences between the two cultivars with different cold-resistance capacities were found when the in-vitro translation products were compared. The results obtained demonstrate that several mRNAs are specifically expressed as a response to cold treatment in barley coleoptiles. PMID- 24212748 TI - Germination-associated events and the desiccation sensitivity of recalcitrant seeds - a study on three unrelated species. AB - The storage behaviour of recalcitrant seeds was assessed using three diverse species: a gymnosperm, Araucaria angustifolia (Bert.) O. Kuntze; a herbaceous monocotyledon, Scadoxus membranaceus (Bak.) Friis Nordal; and a woody dicotyledon, Landolphia kirkii Dyer. Seeds were stored under conditions of high relative humidities that maintained seed moisture content and under low relative humidities that caused drying. At regular intervals moisture content was determined, germinability assessed and the ultrastructure of radicle meristem cells examined. Under storage at high relative humidity, seed moisture content was maintained at the original level and subcellular germination events were initiated in the short-term. Such seeds showed enhanced rates of germination when removed from storage and planted. Long-term storage under these conditions resulted in the initiation of subcellular damage which intensified with time and ultimately resulted in the loss of viability. The rate at which germination events proceeded varied among the three species, and could be directly correlated with the period of viability retention under humid storage conditions. Storage under desiccating conditions resulted in subcellular damage and rapid loss of viability. The rate at which the seeds dried varied among the three species. The proportion of water loss tolerated by the different species before loss of viability, correlated with the rate of drying. The storage behaviour of the seeds of these three species is discussed in terms of a previously described model. PMID- 24212749 TI - Characterization of a protein-kinase activity associated with phytochrome from etiolated oat (Avena sativa L.) seedlings. AB - A protein-kinase activity which is co-purified with phytochrome from etiolated oat seedlings was investigated in some detail. Whereas phytochrome was always phosphorylated in solution (together with some contaminating protein bands), radioactive phosphate was not found in the phytochrome band after native gel electrophoresis and incubation of the entire gel with labeled ATP. Since protein kinases are usually autophosphorylated under these conditions, the result shows that the kinase activity does not reside in the phytochrome molecule itself. Radioactivity was exclusively detected in a band with the apparent molecular weight 450 kDa; sodium-dodecyl-sulfate gel electrophoresis revealed an apparent molecular weight of 60 kDa for the phosphorylated subunit. The N-terminal amino acid sequence A L E S A (G) K Q (L) V P W was determined for this subunit which is a potential candidate for the protein kinase. The optimum conditions (pH, metal ion concentration) and kinetics of the phosphorylation reaction were determined. The presumed connection between proteinkinase activity and the signal chain leading from the far-red-absorbing form of phytochrome to physiological responses still awaits elucidation. PMID- 24212750 TI - Electrofusion of protoplasts from celery (Apium graveolens L.) with protoplasts from the filamentous fungus Aspergillus nidulans. AB - A method was developed for electrofusion of higher-plant protoplasts from celery and protoplasts from the filamentous fungus Aspergillus nidulans. Initially, methods for the fusion of protoplasts from ecch species were determined individually and, subsequently, electrical parameters for fusion between the species were determined. Pronase-E treatment and the presence of calcium ions markedly increased celery protoplast stability under the electrical conditions required and increased fusion frequency with A. nidulans protoplasts. A reduction in protoplast viability was observed after electrofusion but the majority of the protoplasts remained viable over a 24-h incubation period. A small decline in protoplast respiration rate occurred during incubation but those celery protoplasts fused with A. nidulans protoplasts showed elevated respiration rates for 3 h after electrofusion. PMID- 24212751 TI - Kinetin-induced stimulation of electrogenic pumping in soybean suspension cultures is unrelated to signal transduction. AB - Primary modes of action of cytokinins have been thought to involve stimulation of the electrogenic H(+) pump and-or opening of plasmamembrane Ca(2+) channels. In order to test these hypotheses, rapid changes in membrane transport in response to cytokinin application were studied in heterotrophic suspension-cultured callus of soybean (Glycine max (L.) Merr.) using electrophysiological techniques. Kinetin (N(6)-furfurylaminopurine; 2 MUM) elicited membrane hyperpolarization of 13+/-1 mV. This effect occurred even at membrane poteintials more negative than the most negative ionic equilibrium potential, and therefore might have resulted either from stimulation of the electrogenic pump, or from closure of ionic channels. The former mechanism of action appears most likely because (i) kinetin induced membrane hyperpolarization is not accompanied by a significant change in plasma-membrane resistivity and (ii) hyperpolarization is abolished by cyanide, which inhibits electrogenic pump activity by depletion of cellular ATP.Electrogenic pumping is also activated by two other cytokinins: N(6) (benzyl)adenine and trans-zeatin. However, it is unlikely that the hormonal effect on electrogenesis is directly related to transduction of the cytokinin signal, for the following reasons: (i) hormonally inactive, but chemically related compounds (cis-zeatin, adenine) also elicited membrane hyperpolarization; (ii) hormonally active, N(9)-substituted cytokinins failed to stimulate electrogenesis; (iii) the chemically unrelated cytokinin N,N'-diphenylurea also failed to stimulate electrogenesis.The results imply that the kinetin effect on electrogenic pumping is related to adenine, or its metabolism, and not hormonal action. Adenine was absorbed by soybean cells, but not in sufficient quantities to have a significant effect on adeninenucleotide pools. It appears likely that the control of electrogenesis requires either the presence of a purine free base (i.e. no substituents at the N(9) position) or phosphoribosylation of the free base. No evidence was found for cytokinin-induced Ca(2+)-channel opening, though it is argued that such an event might be physiologically relevant, yet undetectable with the methods employed. It is essential that future studies on cytokinin signal transduction - especially as they relate to membrane transport - take into account the possibility that metabolic effects unrelated to hormone action are dominant. PMID- 24212752 TI - Inhibition of stomatal opening in sunflower leaves by carbon monoxide, and reversal of inhibition by light. AB - When leaves of Helianthus annuus, whose stomates had been opened in the dark in the absence of CO2, were exposed to 25% carbon monoxide (CO), stomatal conductivity for water vapor decreased from about 0.4 to 0.2 cm.s(-1). The CO effect on stomatal aperture required a CO/O2 ratio of about 25. As this ratio was decreased the stomata opened, indicating that inhibitio of cytochrome-c oxidase by CO is competitive in respect to O2. Photosynthetically active red light was unable to reverse CO-induced stomatal closure even at high irradiances, when CO2 was absent. When it was present, stomatal opening was occasionally, but not consistently observed. Carbon monoxide did not inhibit photosynthetic carbon reduction in leaves of Helianthus.In contrast to red light, very weak blue light (405 nm) increased the stomatal aperture in the presence of CO. It also increased leaf ATP/ADP ratios which had been decreased in the presence of CO. The blue light effect was not related to photosynthesis. Neither could it be explained by photodissociation of the cytochrome a 3-CO complex which has an absorption maximum at 430 nm. The data indicate that ATP derived from mitochondrial oxidative phosphorylation provides energy for stomatal opening in sunflower leaves in the dark as well as in the light. Indirect transfer of ATP from chloroplasts to the cytosol via the triose phosphate/phosphoglycerate exchange which is mediated by the phosphate translocator of the chloroplast envelope can support stomatal opening only if metabolite concentrations are high enough for efficient shuttle transfer of ATP. Blue light causes stomatal opening in the presence of CO by stimulating ATP synthesis. PMID- 24212753 TI - Calcium influx at the plasmalemma of isolated guard cells of Commelina communis : Effects of abscisic acid. AB - The influx of (45)Ca into isolated guard cells of Commelina communis L. has been measured, using short uptake times, and washing in ice-cold La(3+)-containing solutions to remove extracellular tracer after the loading period. Over 0.5-4 min the uptake was linear with time, through the origin. Over 20-200MUM external Ca(2+) the influx measured with 10-20 mM external KCl was in the range 0.3-2.3 pmol.cm(-2).s(-1) (on the basis of estimated guard-cell area); with only 1 mM KCl externally the (45)Ca influx was significantly reduced, in the range 0.3-1.1 pmol.cm(-2).s(-1) for external Ca(2+) of 50-100 MUM. The results indicate that the Ca-channel is voltage-sensitive, opening with depolarisation. No consistent effect of the addition of abscisic acid could be found. In different experiments, on the addition of 0.1 mM abscisic acid the Ca(2+) influx was sometimes stimulated by 28-79%, was sometimes unaffected, and was sometimes inhibited by 16 29%. The results rule out a long-lasting stimulation of (45)Ca influx by ABA, but they do not rule out a transient stimulation followed by inhibition, perphaps as a consequence of down-regulation of Ca(2+) influx by increasing cytoplasmic Ca(2+). The hypothesis that ABA may act via an action on Ca(2+) influx, increasing cytoplasmic Ca(2+), with consequent effects on voltage-dependent and Ca(2+)-dependent ion channels in both plasmalemma and tonoplast, is neither proved nor disproved by these results. PMID- 24212754 TI - Applicability of the chemiosmotic polar diffusion theory to the transport of indol-3yl-acetic acid in the intact pea (Pisum sativum L.). AB - The transport of exogenous indol-3yl-acetic acid (IAA) from the apical tissues of intact, light-grown pea (Pisum sativum L. cv. Alderman) shoots exhibited properties identical to those associated with polar transport in isolated shoot segments. Transport in the stem of apically applied [1-(14)C]-or [5-(3)H]IAA occurred at velocities (approx. 8-15 mm.h(-1)) characteristic of polar transport. Following pulse-labelling, IAA drained from distal tissues after passage of a pulse and the rate characteristics of a pulse were not affected by chases of unlabelled IAA. However, transport of [1-(14)C]IAA was inhibited through a localised region of the stem pretreated with a high concentration of unlabelled IAA or with the synthetic auxins 1-napthaleneacetic acid and 2,4 dichlorophenoxyacetic acid, and label accumulated in more distal tissues. Transport of [1-(14)C]IAA was also completely prevented through regions of the intact stem treated with N-1-naphthylphthalamic acid (NPA) and 2,3,5 triiodobenzoic acid.Export of IAA from the apical bud into the stem increased with total concentration of IAA applied (labelled+unlabelled) but approached saturation at high concentrations (834 mmol.m(-3)). Transport velocity increased with concentration up to 83 mmol.m(-3) IAA but fell again with further increase in concentration.Stem segments (2 mm) cut from intact plants transporting apically applied [1-(14)C]IAA effluxed 93% of their initial radioactivity into buffer (pH 7.0) in 90 min. The half-time for efflux increased from 32.5 to 103.9 min when 3 mmol.m(-3) NPA was included in the efflux medium. Long (30 mm) stem sections cut from immediately below an apical bud 3.0 h after the apical application of [1-(14)C]IAA effluxed IAA when their basal ends, but not their apical ends, were immersed in buffer (pH 7.0). Addition of 3 mmol.m(-3) NPA to the external medium completely prevented this basal efflux.These results support the view that the slow long-distance transport of IAA from the intact shoot apex occurs by polar cell-to-cell transport and that it is mediated by the components of IAA transmembrane transport predicted by the chemiosmotic polar diffusion theory. PMID- 24212755 TI - Sulphate influx in wheat and barley roots becomes more sensitive to specific protein-binding reagents when plants are sulphate-deficient. AB - When young wheat (Triticum aestivum L.) or barley (Hordeum vulgare L.) plants were deprived of an external sulphate supply (-S plants), the capacity of their roots to absorb sulphate, but not phosphate or potassium, increased rapidly (derepression) so that after 3-5 d it was more than tenfold that of sulphate sufficient plants (+S plants). This increased capacity was lost rapidly (repression) over a 24-h period when the sulphate supply was restored. There was little effect on the uptake of L-methionine during de-repression of the sulphate transport system, but S input from methionine during a 24-h pretreatment repressed sulphate influx in both+S and-S plants.Sulphate influx of both+S and-S plants was inhibited by pretreating roots for 1 h with 4,4' diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) at concentrations > 0.1 mol . m(-3). This inhibition was substantially reversed by washing for 1 h in DIDS free medium before measuring influx. Longer-term pretreatment of roots with 0.1 mol.m(-3) DIDS delayed de-repression of the sulphatetransport system in-S plants but had no influence on+S plants in 3 d.The sulphydryl-binding reagent, n ethylmaleimide, was a very potent inhibitor of sulphate influx in-S roots, but was much less inhibitory in +S roots. Its effects were essentially irreversible and were proportionately the same at all sulphate concentrations within the range of operation of the high-affinity sulphate-transport system. Inhibition of influx was 85-96% by 300 s pretreatment by 0.3 mol.m(-3) n-ethylmaleimide. No protection of the transport system could be observed by including up to 50 mol.m(-3) sulphate in the n-ethylmaleimide pre-treatment solution. A similar differential sensitivity of-S and+S plants was seen with p-chloromercuriphenyl sulphonic acid.The arginyl-binding reagent, phenylglyoxal, supplied to roots at 0.25 or 1 mol.m(-3) strongly inhibited influx in-S wheat plants (by up to 95%) but reduced influx by only one-half in+S plants. The inhibition of sulphate influx in-S plants was much greater than that of phosphate influx and could not be prevented by relatively high (100 mol.m(-3) sulphate concentrations accompanying phenylglyoxal treatment. Effects of phenylglyoxal pretreatment were unchanged for at least 30 min after its removal from the solution but thereafter the capacity for sulphate influx was restored. The amount of 'new' carrier appearing in-S roots was far greater than in+S roots over a 24-h period.The results indicate that, in the de-repressed state, the sulphate transporter is more sensitive to reagents binding sulphydryl and arginyl residues. This suggests a number of strategies for identifying the proteins involved in sulphate transport. PMID- 24212756 TI - Some relationships between contents of photosynthetic intermediates and the rate of photosynthetic carbon assimilation in leaves of Zea mays L. AB - The relationship between the gas-exchange characteristics of attached leaves of Zea mays L. and the contents of photosynthetic intermediates was examined at different intercellular partial pressure of CO2 and at different irradiances at a constant intercellular partial pressure of CO2. (i) The behaviour of the pools of the C4-cycle intermediates, phosphoenolpyruvate and pyruvate, provides evidence for light regulation of their consumption. However, light regulation of phosphoenolpyruvate carboxylase does not influence the assimilation rate at limiting intercellular partial pressures of CO2. (ii) A close correlation between the pools of phosphoenolpyruvate and glycerate-3-phosphate exists under many different flux conditions, consistent with the notion that the pools of C4 and C3 cycles are connected via the interconversion of glycerate-3-phosphate and phosphoenolpyruvate. (iii) The ratio of triose-phosphate to glycerate-3-phosphate is used as an indicator of the availability of ATP and NADPH. Changes of this ratio with CO2 and with irradiance are compared with results obtained in C3 leaves and indicate that the mechanism of regulation of carbon assimilation by light in leaves of C4 plants may differ from that in C3 plants. (iv) The behaviour of the ribulose-1,5-bisphosphate pool with CO2 and irradiance is contrasted with the behaviour of these pools measured in leaves of C3 plants. PMID- 24212757 TI - Metabolism of [1,2-(3)H]gibberellin A 4 by epicotyls and cell-free preparations from Phaseolus coccineus L. seedlings. AB - Cell-free systems were prepared from germinating seed and seedlings of Phaseolus coccineus. Gibberellin A4 (GA4)-metabolising activity was detected in vitro using preparations from roots, shoots and cotyledons of germinating seed, but only up to 24 h after imbibition. Cell-free preparations from cotyledons converted [(3)H]GA4 to GA1, GA34, GA4-glucosyl ester and a putative O-glucoside of GA34, and, in addition converted [(3)H]GA1 to GA8. Preparations from embryo tissues contained 2beta-hydroxylase activity, converting [(3)H]GA4 to GA34 and [(3)H]GA1 to GA8.The presence of GA-metabolising enzymes was also indicated by in-vivo feeds of [(3)H]GA4 to epicotyls of intact 4-d-old seedlings, which resulted in the accumulation of GA1, GA8, GA3-3-O-glucoside, GA4-glucosyl ester, GA8-2-O glucoside and a putative O-glucoside of GA34. Gibberellin A1 was the first metabolite detected, 15 min after application of [(3)H]GA4, but after 24 h most of the label was associated with GA8-2-O-glucoside. Over 90% of the recovered radioactivity was found in the shoot. Within the shoot, movement was preferentially acropetal, and was not dependent upon metabolism of the applied [(3)H]GA4. PMID- 24212758 TI - A rare instance of retrosternal goitre presenting with obstructive sleep apnoea in a middle-aged person. AB - INTRODUCTION: In endemic goitre areas, 20% of the population over 70 will have retrosternal goitre.(12) Obstructive sleep apnoea (OSA) occurs when there are repeated episodes of complete or partial blockage of the upper airway during sleep. PRESENTATION OF CASE: A 55-year-old man was being treated for obstructive sleep apnoea, came with stridor worsening over the 2 and was advised CPAP ventilation. In our institution, he was diagnosed to have goitre with retrosternal extension with no hypo/hyperthyroidism. He was an obese (BMI - 30Kg/m(2)) male with a short, broad neck and clinically no obvious swelling in the neck. He had stridor, with positive Kocher's test as well as Pemberton's sign. His TFT's were normal and CT scan revealed widening of superior mediastinum. Patient was pre-medicated with low dose (0.1MUg) fentanyl, and induced with inhalational anaesthesia (sevoflourane). Endotracheal intubation was done using 6 no. ET tube, without muscle relaxation, and the thyroid was removed through a conventional Kocher's incision. Thyroid was enlarged 25cm by 10cm in retrosternal position. Postoperatively, pt was reversed and shifted to ICU, was monitored for the next 24hours. He was extubated uneventfully the next morning. Patient had a good post-op recovery and was discharged on the 7th post-op day. DISCUSSION: Terms such as retrosternal, substernal, intrathoracic, or mediastinal have been used to describe a goitre that extends beyond the thoracic inlet. However, there is a lack of consensus regarding the exact definition of a retrosternal goitre (RSG).(1) The majority of patients present with shortness of breath or asthma like symptoms (68.8%), as was the case in the studied patient. Other modes of presentation include neck mass (75%), hoarseness of voice (37.5%), dysphagia (31.3%), stridor/wheezing (19%), or SVC obstruction. Upper airway obstruction due to thyroid gland has been reported up to 31%(2) and difficulty in intubation has been reported in 11%.(3) Central airway obstruction produces symptoms of dyspnoea, stridor, or obstructive pneumonia and is often misdiagnosed as asthma.(4) The CT scan was the most useful tool showing the nature and extent of the lesion in the reported case. In a recent publication, the CT scan was considered the gold-standard preoperative radiological investigation.(5) Surgery is the only effective treatment for retrosternal goitres. In most cases, suppressive therapy with thyroxine is ineffective in reducing the size of multinodular goitres;(7,8) radio-iodine therapy is both generally ineffective in large goitres(8) and may induce acute inflammation and swelling of the gland with the potential for airway obstruction. The operation of choice is usually a total thyroidectomy. Only around 2% of patients undergoing thyroidectomy for retrosternal goitre will require surgical access other than a standard collar incision (either manubriotomy, sternotomy or thoracotomy).(9) CONCLUSION: Despite all the advances in investigative modalities, retrosternal goitre still exists in 20% of patients over 70 years in endemic regions. It has to be recognised that it can be a cause of obstructive sleep apnoea. Early detection and prompt management goes a long way in decreasing the morbidity and mortality in patients with RSG. PMID- 24212759 TI - Endoscopic removal of large orbito-ethmoidal osteoma in pediatric patient: Case report. AB - INTRODUCTION: Osteoma is a benign slow growing bone tumor with a prevalence of 3% of all benign paranasal sinuses tumors, with a peak incidence between the fourth and sixth decades, mostly involving frontal sinuses.(1) PRESENTATION OF CASE: We present a case of a large right ethmoidal sinus osteoma in a 12-year-old boy, complaining of frontal headaches and excessive lacrimation of the right eye. CT scan showed a very large tumor in the right anterior ethmoidal sinus (30mm*25mm*15mm). DISCUSSION: Large osteomas of the paranasal sinuses are usually resected by external approaches. However, the minimally invasive endonasal approach, which minimizes external facial scarring, is challenging for such large lesions in pediatrics. In the presented case, the osteoma was successfully resected exclusively by endoscopy-guided endonasal approach assisted by neuronavigation, with no peri or postoperative complications. CONCLUSION: An endoscopic approach assisted with neuronavigation may be a minimally invasive and safe procedure for managing large osteoma of the ethmoidal sinus in pediatrics patients. PMID- 24212760 TI - Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. AB - Early detection and treatment are critical in the management of renal cell carcinoma (RCC). However, there is no standard serum biomarker to facilitate early diagnosis or prognostic stratification in patients with RCC. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for diagnosis and prognosis in patients with several types of cancers. Further, many studies using miRNA microarray analysis demonstrated that miR-210 expression in clear cell carcinoma (CCC), which is the largest subtype of RCC, was significantly upregulated in tumor tissue. Therefore, we investigated whether serum miR-210 could be a useful biomarker for the diagnosis and progression of CCC. This study included 34 CCC patients and 23 healthy controls (HC). First, we analyzed tissue miR-210 levels in tumor tissues and matched normal tissues from the 34 CCC patients. Second, we investigated the serum miR-210 levels in the 34 CCC patients and the 23 HC patients. Real-time polymerase chain reaction (PCR) was used to measure miRNA levels. Moreover, we examined the correlation between serum miR-210 levels and the clinicopathological parameters. Among patients with CCC, expression of miR-210 was higher in tumor tissues compared to normal tissues (P<0.001). Serum miR-210 levels were higher in CCC patients compared to HCs (P=0.001). Receiver operating characteristic (ROC) curve analysis showed an area under the ROC curve (AUC) of 0.77 (95% confidence interval, 0.65-0.89) and a sensitivity and specificity of 65 and 83%, respectively. In addition, there was no significant association between serum miR-210 levels and age, sex, tumor size or existence of metastasis at diagnosis among the 34 CCC patients. In conclusion, serum miR-210 upregulation may occur in the early stage of CCC and serum miR-210 can be a useful biomarker for early CCC in humans. PMID- 24212762 TI - Analysis of manganese superoxide dismutase (MnSOD Ala-9Val) and glutathione peroxidase (GPx1 Pro 198 Leu) gene polymorphisms in psoriasis. AB - Recent studies have suggested the involvement of increased reactive oxygen species levels and decreased antioxidant system functions in psoriasis pathogenesis. In this study, we aimed to examine to investigate possible associations between the manganese superoxide dismutase (MnSOD Ala-9Val) and glutathione peroxidase (GPx1 Pro198Leu) polymorphisms and psoriasis susceptibility and disease progression in a Turkish population. The study group consisted of 100 unrelated patients with psoriasis and 167 unrelated healthy controls. Genomic DNA was extracted from peripheral leukocytes of whole blood which were obtained from all patients and control subjects. Genotyping was performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms by a method based on PCR amplification and detection of polymorphisms with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies were compared between patients with psoriasis and 106 healthy control subjects. There was no significant difference between the MnSOD Ala-9Val single nucleotide polymorphism (SNP) genotype distributions and allele frequencies of the psoriasis patients and the control group (p = 0.99 and p = 0.89, respectively). There was also no significant difference between distributions of the genotype or allele frequencies of the GPx1 Pro198Leu SNP of the patient groups and control subjects (p = 0.99 and p = 0.96, respectively). Also, no significant difference was found between clinical severity of psoriasis and MnSOD Ala-9Val and GPx1 Pro198Leu polymorphism. This is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms and psoriasis susceptibility and disease progression in the Turkish population even if no significant difference was found between patient groups and control subjects. Further studies with large cohort on different populations and ethnicities will be able to better clarify the association. PMID- 24212761 TI - Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson's disease. AB - Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either detrimental or beneficial effects in the central nervous system (CNS). Harnessing the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of Parkinson's disease (PD). However, the epigenetic mechanism that regulates microglia polarization remains elusive. Here, we reported that histone H3K27me3 demethylase Jumonji domain containing 3 (Jmjd3) was essential for M2 microglia polarization. Suppression of Jmjd3 in N9 microglia inhibited M2 polarization and simultaneously exaggerated M1 microglial inflammatory responses, which led to extensive neuron death in vitro. We also observed that the suppression of Jmjd3 in the substantia nigra (SN) in vivo dramatically caused microglial overactivation and exacerbated dopamine (DA) neuron death in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxicated mouse model of PD. Moreover, we showed that the Jmjd3 level was lower in the midbrain of aged mice, which was accompanied by an elevated level of H3K27me3 and an increased ratio of M1 to M2 markers, suggesting that aging is an important factor in switching the microglia phenotypes. Overall, our studies indicate that Jmjd3 is able to enhance the polarization of M2 microglia by modifying histone H3K27me3, and therefore it has a pivotal role in the switch of microglia phenotypes that may contribute to the immune pathogenesis of PD. PMID- 24212763 TI - Educational inequalities in three smoking-related causes of death in 18 European populations. AB - INTRODUCTION: Smoking is an important determinant of socioeconomic inequalities in mortality in many countries. As the smoking epidemic progresses, updates on the development of mortality inequalities attributable to smoking are needed. We provide estimates of relative and absolute educational inequalities in mortality from lung cancer, aerodigestive cancers, and chronic obstructive pulmonary disease (COPD)/asthma in Europe and assess the contribution of these smoking related diseases to inequalities in all-cause mortality. METHODS: We use data from 18 European populations covering the time period 1998-2007. We present age adjusted mortality rates, relative indices of inequality, and slope indices of inequality. We also calculate the contribution of inequalities in smoking-related mortality to inequalities in overall mortality. RESULTS: Among men, relative inequalities in mortality from the 3 smoking-related causes of death combined are largest in the Czech Republic and Hungary and smallest in Spain, Sweden, and Denmark. Among women, these inequalities are largest in Scotland and Norway and smallest in Italy and Spain. They are often larger among men and tend to be larger for COPD/asthma than for lung and aerodigestive cancers. Relative inequalities in mortality from these conditions are often larger in younger age groups, particularly among women, suggesting a possible further widening of inequalities in mortality in the coming decades. The combined contribution of these diseases to inequality in all-cause mortality varies between 13% and 32% among men and between -5% and 30% among women. CONCLUSION: Our results underline the continuing need for tobacco control policies, which take into account socioeconomic position. PMID- 24212764 TI - Prevalence and harm perceptions of various tobacco products among college students. AB - INTRODUCTION: Although use of non-cigarette alternative tobacco products (ATPs) is increasingly prevalent in the United States, little is known about the varying patterns of tobacco use among college students. This study examined prevalence of ATP use and differences across 4 groups of students (nontobacco, cigarette-only, polytobacco, and ATP-only users) on perceptions of danger and beliefs about government safety evaluation of tobacco products. METHODS: An online survey was administered to 5,028 students attending 7 public universities within a larger university system (M age = 20.5 years, 59.6% female, 54.6% Hispanic/Latino). Multivariate analyses were conducted to investigate differences between the 4 groups on perceived danger of tobacco products and beliefs regarding government safety evaluation of these products. RESULTS: Prevalence of ATP use among the sample ranged from 0.4% for dissolvable tobacco to 10.8% for hookah. Group membership was significantly associated with perceived danger of each tobacco product, whereby cigarette-only and ATP-only users reported significantly higher levels of perceived danger for most ATPs than did polytobacco users. Furthermore, cigarette-only, polytobacco, and ATP-only users were significantly more likely than nonusers to believe that the government evaluates some tobacco products for safety. CONCLUSIONS: ATP use among young adult college students is prevalent. Furthermore, students who use ATPs in conjunction with cigarettes (i.e., polytobacco users) appear to be at highest risk for the continuation and subsequent dependence on nicotine, given their danger perceptions and beliefs of government evaluation. Future research examining trajectories of use, particularly among polytobacco users, is needed. PMID- 24212765 TI - Clinical, confocal, and morphological investigations on the cornea in human mucopolysaccharidosis IH-S. AB - PURPOSE: The aim was to describe the confocal and histological findings of 2 corneas from a patient with an advanced case of type I mucopolysaccharidoses Hurler-Scheie disease (MPS IH-S). METHODS: Both corneas from an MPS IH-S-affected patient were examined in vivo using confocal microscopy and then removed and processed for evaluation using light microscopy and transmission and scanning electron microscopy. RESULTS: Confocal microscopy evaluation showed basal epithelial cells with either diffuse or granular hyperreflectivity. Keratocytes were highly reflective determining a web-shaped stromal appearance. Endothelial cells were barely visible. The histopathological study demonstrated superficial cells with apical microfolds, small vesicles, and evident intercellular junctions. The wing cells showed either well-evident tonofilaments and small peripheral vesicles, or large paranuclear vesicles. The basal cells showed polygonal shapes, many small vesicles, and enlarged intercellular spaces. The Bowman layer was either normal or thinner and was formed by variably electron dense material. In the stroma, irregularly oriented lamellae, many vesicle-filled keratocytes, and intercellular granular material were present. The Descemet membrane was normal, whereas the corneal endothelium showed marked degenerative changes. CONCLUSIONS: The confocal alterations appeared consequent to the anomalous accumulation of material. The histopathological images gave a clue to better understand the corneal changes demonstrated by the confocal studies in MPS IH-S. PMID- 24212766 TI - Short-term changes in tear volume after blepharoptosis repair. AB - PURPOSE: The aim was to evaluate tear volume change by using videomeniscometry before and after blepharoptosis surgery. METHODS: Fifty-nine eyes of 36 patients with blepharoptosis without lacrimal duct obstruction or other eyelid diseases were examined. All the patients underwent levator advancement, and the tear volume was evaluated preoperatively and 1.5 months postoperatively. The margin reflex distance-1 was determined from photographs, and the tear volume was determined by the measurement of tear meniscus radius using videomeniscometry. RESULTS: The mean margin reflex distance-1 was significantly increased after performing a blepharoptosis surgery (0.13 +/- 1.13 mm preoperatively vs. 3.18 +/- 0.85 mm postoperatively, P < 0.001). The average tear meniscus radius was significantly decreased (0.31 +/- 0.16 mm preoperatively vs. 0.23 +/- 0.08 mm postoperatively, P < 0.001). A postoperative reduction in the tear meniscus radius was noted in 46 eyes (78%) of 31 patients, and no reduction was noted in 13 eyes (22%) of 12 patients. Preoperative higher tear meniscus radius values were more likely to be decreased (P < 0.01). CONCLUSIONS: The tear volume was decreased after the blepharoptosis surgery was performed, especially for an initially high tear volume. PMID- 24212767 TI - A conversation with great doctors. PMID- 24212768 TI - Could Thoracoscore predict postoperative mortality in patients undergoing pneumonectomy? AB - OBJECTIVES: Thoracoscore is incorporated in the new British Thoracic Society and National Institute of Health and clinical Excellence guidelines to evaluate the operative mortality risk of patients undergoing thoracic surgery. This study examines the accuracy of Thoracoscore in predicting postoperative mortality in patients undergoing pneumonectomy. METHODS: All patients who underwent pneumonectomy from January 1998 to March 2008 were included. Thoracoscore was calculated based on the following variables: age, sex, American Society of Anaesthesiologists' class, performance status classification, dyspnoea score, priority of surgery, procedure class, Diagnosis group and comorbidities score. RESULTS: Two hundred and forty-three patients with a mean age of 63 +/- 9 years were included and 81% were male. The predicted postoperative mortality based on Thoracoscore was 8 +/- 2.6% (95% confidence interval (CI) 4.56-11.43), while actual in-hospital mortality was 4.5% (11/243) (95% CI 1.87-7.12). 54% (6/11) of in-hospital mortality was of those who were >70 years old and 73% (8/11) of patients who died in hospital were male. Nine of 11 (82%) patients had pneumonectomy for malignancy. Thoracoscore was divided into four risk groups: low (0-3), moderate (3.1-5), high (5.1-8) and very high (>8). It underestimated mortality in low-risk group while overestimated in high-risk groups. The 30-day, 1-year, 2-year and 3-year observed mortalities were 5.3, 29, 43 and 55%, respectively. CONCLUSIONS: Although advanced age, the male sex and malignancy proved to be strong predictors of in-hospital mortality in our study, Thoracoscore failed to predict accurate risk of in-hospital mortality in pneumonectomy patients in this study. Further studies are required to validate the Thoracoscore in different subgroups of thoracic surgery. PMID- 24212769 TI - A new endoscopic standardized grading system for macroscopic central airway complications following lung transplantation: the MDS classification. AB - OBJECTIVES: After lung transplant, between 9 and 13% of bronchial anastomoses develop complications severe enough to warrant therapeutic intervention. These complications include stenosis, dehiscence, granulation tissue, bronchomalacia and fistula. Most of these have already been included in a classification or another, but none of these have been universally accepted. Moreover, no grading system has integrated all of these complications. The Groupe Transplantation (GT) (Transplant Group), from the Societe de Pneumologie de Langue Francaise (SPLF) [French Language Pulmonology Society], maintains a prospective national registry of lung transplants performed in France. The GT has mandated the Groupe d'Endoscopie de Langue Francaise (GELF), also from the SPLF, to develop an endoscopic classification, in order to describe the macroscopic aspect of the bronchial anastomoses, and downhill airways, using a standardized and exhaustive grading system. METHODS: An endoscopic classification that would take into account the three major aspects of the description of bronchial anastomoses was elaborated. The first parameter is the macroscopic aspect (M), the second, the diameter (D) of the anastomosis and the third, the sutures (S) of the anastomosis. This classification was then submitted to expert bronchoscopists from nine centres, responsible for lung transplants in France, for their opinion, using a five-item questionnaire, according to the Delphi methodology. RESULTS: After the first round of consultation, all experts (100%) agreed on Questions 1 and 4. Answers were positive for Questions 2 (59%), 3 (56.25%) and 5 (70%). A modified classification, incorporating propositions from the first round, was then submitted. This second round allowed a consensus to be reached between all experts: the MDS classification. Each parameter (M, D and S) can be classified from 0 to 3. For M and D, it is possible to determine the extent of abnormalities downhill from the anastomosis into four subgroups (a, b, c or d). For S, the localization of abnormalities can be divided between two subgroups (e and f). CONCLUSION: The MDS classification, established by a consensus of French experts in bronchoscopy, could represent a standardized, universally acceptable system to describe central airway complications after lung transplant. PMID- 24212770 TI - Role of methionine adenosyltransferase genes in hepatocarcinogenesis. AB - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Detection of HCC can be difficult, as most of the patients who develop this tumor have no symptoms other than those related to their longstanding liver disease. There is an urgent need to understand the molecular mechanisms that are responsible for the development of this disease so that appropriate therapies can be designed. Methionine adenosyltransferase (MAT) is an essential enzyme required for the biosynthesis of S-adenosylmethionine (AdoMet), an important methyl donor in the cell. Alterations in the expression of MAT genes and a decline in AdoMet biosynthesis are known to be associated with liver injury, cirrhosis and HCC. This review focuses on the role of MAT genes in HCC development and the scope for therapeutic strategies using these genes. PMID- 24212771 TI - To die or to survive, a fatal question for the destiny of prostate cancer cells after androgen deprivation therapy. AB - Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/beta-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge. PMID- 24212772 TI - Epidermal growth factor receptor in pancreatic cancer. AB - Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer. PMID- 24212773 TI - Epigenetic regulation of glucose transporters in non-small cell lung cancer. AB - Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. PMID- 24212774 TI - Cancer stem cells of differentiated B-cell malignancies: models and consequences. AB - The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a "top-to-bottom" clonal hierarchy from memory B-cells and a "bottom-to-top" model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity. PMID- 24212775 TI - Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience. AB - Abdominal Non-Hodgkin lymphomas (NHL) are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI), Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15). Thirty patients (86%) presented with abdominal pain, 23 patients (66%) presented with abdominal mass and distention, 13 patients (34%) presented with weight loss, and intestinal obstruction occurred in six patients (17%). The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively). Burkitt's lymphoma was the most common histological type in 29 patients (83%). Ten (28.5%) stage II (group A) and 25 (71.5%) stage III (group B). Complete resections were performed in 10 (28.5%), debulking in 6 (17%) and imaging guided biopsy in 19 (54%). A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months). The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL. PMID- 24212776 TI - The role of nrf2 and cytoprotection in regulating chemotherapy resistance of human leukemia cells. AB - The Nrf2 anti-oxidant response element (ARE) pathway plays an important role in regulating cellular anti-oxidants. Under normal cellular conditions Nrf2 can be described as an anti-tumor molecule due to its induction of cytoprotective genes which protect cells from electrophile and oxidative damage. However in cancerous cells, Nrf2 takes on a pro-tumoral identity as the same cytoprotective genes can enhance resistance of those cancer cells to chemotherapeutic drugs. Such Nrf2 regulated cytoprotective genes include heme oxygenase-1 (HO-1), which has been shown to protect human leukemia cells from apoptotic signals. Moreover, a relationship between Nrf2 and the nuclear factor-kappaB (NF-kappaB) signaling pathway has been recently identified, and is now recognized as an important cross talk mechanism by which Nrf2 can overcome apoptosis and provide cells with reduced sensitivity towards chemotherapeutic agents. In recent years a number of important research papers have highlighted the role of Nrf2 in providing protection against both current and new chemotherapeutic drugs in blood cancer. This review will provide a synopsis of these research papers with an aim to carefully consider if targeting Nrf2 in combination with current or new chemotherapeutics is a viable strategy in the more effective treatment of blood cancers. PMID- 24212777 TI - Predictive and prognostic factors in colorectal cancer: a personalized approach. AB - It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-beta. PMID- 24212778 TI - Role of gene methylation in antitumor immune response: implication for tumor progression. AB - Cancer immunosurveillance theory has emphasized the role of escape mechanisms in tumor growth. In this respect, a very important factor is the molecular characterization of the mechanisms by which tumor cells evade immune recognition and destruction. Among the many escape mechanisms identified, alterations in classical and non-classical HLA (Human Leucocyte Antigens) class I and class II expression by tumor cells are of particular interest. In addition to the importance of HLA molecules, tumor-associated antigens and accessory/co stimulatory molecules are also involved in immune recognition. The loss of HLA class I antigen expression and of co-stimulatory molecules can occur at genetic, transcriptional and post-transcriptional levels. Epigenetic defects are involved in at least some mechanisms that preclude mounting a successful host-antitumor response involving the HLA system, tumor-associated antigens, and accessory/co stimulatory molecules. This review summarizes our current understanding of the role of methylation in the regulation of molecules involved in the tumor immune response. PMID- 24212780 TI - Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype. AB - Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFbeta and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology. PMID- 24212781 TI - Contrast-Enhanced Ultrasound (CEUS) for Echographic Detection of Hepato Cellular Carcinoma in Cirrhotic Patients Previously Treated with Multiple Techniques: Comparison of Conventional US, Spiral CT and 3-Dimensional CEUS with Navigator Technique (3DNav CEUS). AB - A commercially available technique named "NAVIGATOR" (Esaote, Italy) easily enables a 3-D reconstruction of a single 2-D acquisition of Contrast Enhanced Ultrasound (CEUS) imaging of the whole liver (with a volumetric correction thanks to the electromagnetic device of NAVIGATOR). Aim of the study was to evaluate this "panoramic" technique in comparison with conventional US and spiral CT in the detection of new hepatic lesions. 144 cirrhotic patients (previously treated for hepato cellular carcinoma (HCC)) in follow-up with detection of 98 new nodules (N), 28 multinodular (Nmulti), 14 loco-regional regrowth (LR) 94 efficaciously treated without new nodules (neg) and four multinodular without new nodules, were submitted to 200 examinations with this new technique from November 2008 to November 2009. 3DNavCEUS was performed using SonoVue (Bracco), as contrast agent, and a machine (Technos MPX, Esaote). Spiral CT and 3DNav CEUS were performed in the same month during follow up. Sens.,Spec.,diagn.-Acc.,PPV and NPV were evaluated; comparison and differences between the techniques were obtained with chi-square (SPSS release-15). Final diagnosis was: 98 new lesions (N) (one to three), 28 multinodular HCC (Nmulti) and 14 loco-regional regrowth (LR); in 94 no more lesions were observed during follow-up; conventional US obtained: 58 N (+18 multinodularN and 8 LR), 40 false negative (+10 Nmulti and 6 LR) (sens:59.2, spec:100%, Diagn Accur:73.6, PPV:100; NPV:70.1); spiral CT obtained: 84N (+26-multinodularN and 14-LR), 14 false-negative (+2-Nmulti), and one false-positive (sens:85.7, spec:97.9%, Diagn Accur:90.9, PPV:97.7; NPV:86.8); 3DNAV obtained: 92N (+28 multinodularN and 14LR), 6 false-negative, and two false positives (sens:93.9, spec:97.9%, Diagn Accur:95.6, PPV:97.9; NPV:93.9). 3-DNav CEUS is significantly better than US and almost similar to spiral CT for detection of new HCC. This technique, in particular, showed the presence of lesions even in the cases not detected with spiral CT. PMID- 24212779 TI - Regulatory T cells in colorectal cancer: from biology to prognostic relevance. AB - Regulatory T cells (Tregs) were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches. PMID- 24212782 TI - Brain cancer stem cells: current status on glioblastoma multiforme. AB - Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM "cancer stem cells" were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings. PMID- 24212784 TI - Targeted alpha therapy approach to the management of pancreatic cancer. AB - Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A" to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (~100 um diameter), causing apoptosis in some 70-90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro-metastatic pancreatic cancer with over-expression of MUC1 and uPA receptors in post-surgical patients with minimal residual disease. The observation of tumor regression in a Phase I clinical trial of targeted alpha therapy for metastatic melanoma indicates that alpha therapy can regress tumors by a process called tumor anti-vascular alpha therapy (TAVAT). As a consequence, this therapy could be indicated for the management of non-surgical pancreatic cancer tumors. PMID- 24212783 TI - Apoptosis and DNA methylation. AB - Epigenetic mechanisms assist in maintaining gene expression patterns and cellular properties in developing and adult tissues. The molecular pathology of disease states frequently includes perturbation of DNA and histone methylation patterns, which can activate apoptotic pathways associated with maintenance of genome integrity. This perspective focuses on the pathways linking DNA methyltransferases and methyl-CpG binding proteins to apoptosis, and includes new bioinformatic analyses to characterize the evolutionary origin of two G/T mismatch-specific thymine DNA glycosylases, MBD4 and TDG. PMID- 24212785 TI - Biomarkers in advanced colorectal cancer: challenges in translating clinical research into practice. AB - The growing number of therapeutic agents and known molecular targets in oncology makes the study and clinical use of biomarkers imperative for improving response and survival, reducing toxicity and ensuring economic sustainability. Colorectal cancer, among others, is at the forefront of development of predictive and prognostic biomarkers; however, the difficulty lies in translating potential biomarkers garnered from retrospective analyses in small numbers of patients to generalizable and affordable biomarkers used worldwide. This review outlines the progress made in prognostic and predictive biomarkers in advanced colorectal cancer (ACRC) from the early use of carcinoembryonic antigen (CEA) to the KRAS mutation and beyond. Future challenges are to incorporate standardized and validated methods preferentially during early phases of drug development linked with sophisticated biostatistical support. New trial designs focusing on biomarkers will be essential not only for better understanding of mechanisms of action, but also to make confident 'go or no-go' decisions. PMID- 24212786 TI - Molecular epidemiology of female lung cancer. AB - Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer. PMID- 24212787 TI - Recent Advance in Biosensors for microRNAs Detection in Cancer. AB - MicroRNAs (miRNAs) are short non-protein-coding RNA molecules that regulate the expression of a wide variety of genes. They act by sequence-specific base pairing in the 3' untranslated region (3'UTR) of the target mRNA leading to mRNA degradation or translation inhibition. Recent studies have implicated miRNAs in a wide range of biological processes and diseases including development, metabolism and cancer, and revealed that expression levels of individual miRNAs may serve as reliable molecular biomarkers for cancer diagnosis and prognosis. Therefore, a major challenge is to develop innovative tools able to couple high sensitivity and specificity for rapid detection of miRNAs in a given cell or tissue. In this review, we focus on the latest innovative approaches proposed for miRNA profiling in cancer and discuss their advantages and disadvantages. PMID- 24212790 TI - Endoscopic palliation for pancreatic cancer. AB - Pancreatic cancer is devastating due to its poor prognosis. Patients require a multidisciplinary approach to guide available options, mostly palliative because of advanced disease at presentation. Palliation including relief of biliary obstruction, gastric outlet obstruction, and cancer-related pain has become the focus in patients whose cancer is determined to be unresectable. Endoscopic stenting for biliary obstruction is an option for drainage to avoid the complications including jaundice, pruritus, infection, liver dysfunction and eventually failure. Enteral stents can relieve gastric obstruction and allow patients to resume oral intake. Pain is difficult to treat in cancer patients and endoscopic procedures such as pancreatic stenting and celiac plexus neurolysis can provide relief. The objective of endoscopic palliation is to primarily address symptoms as well improve quality of life. PMID- 24212789 TI - Colorectal cancer stem cells and cell death. AB - Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem-like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool. PMID- 24212788 TI - Neuropilins: a new target for cancer therapy. AB - Recent investigations highlighted strong similarities between neural crest migration during embryogenesis and metastatic processes. Indeed, some families of axon guidance molecules were also reported to participate in cancer invasion: plexins/semaphorins/neuropilins, ephrins/Eph receptors, netrin/DCC/UNC5. Neuropilins (NRPs) are transmembrane non tyrosine-kinase glycoproteins first identified as receptors for class-3 semaphorins. They are particularly involved in neural crest migration and axonal growth during development of the nervous system. Since many types of tumor and endothelial cells express NRP receptors, various soluble molecules were also found to interact with these receptors to modulate cancer progression. Among them, angiogenic factors belonging to the Vascular Endothelial Growth Factor (VEGF) family seem to be responsible for NRP related angiogenesis. Because NRPs expression is often upregulated in cancer tissues and correlated with poor prognosis, NRPs expression might be considered as a prognostic factor. While NRP1 was intensively studied for many years and identified as an attractive angiogenesis target for cancer therapy, the NRP2 signaling pathway has just recently been studied. Although NRP genes share 44% homology, differences in their expression patterns, ligands specificities and signaling pathways were observed. Indeed, NRP2 may regulate tumor progression by several concurrent mechanisms, not only angiogenesis but lymphangiogenesis, epithelial-mesenchymal transition and metastasis. In view of their multiples functions in cancer promotion, NRPs fulfill all the criteria of a therapeutic target for innovative anti-tumor therapies. This review focuses on NRP-specific roles in tumor progression. PMID- 24212791 TI - Colon Cancer Stem Cells: Bench-to-Bedside-New Therapeutical Approaches in Clinical Oncology for Disease Breakdown. AB - It is widely accepted by the scientific community that cancer, including colon cancer, is a "stem cell disease". Until a few years ago, common opinion was that all neoplastic cells within a tumor contained tumorigenic growth capacity, but recent evidences hint to the possibility that such a feature is confined to a small subset of cancer-initiating cells, also called cancer stem cells (CSCs). Thus, malignant tumors are organized in a hierarchical fashion in which CSCs give rise to more differentiated tumor cells. CSCs possess high levels of ATP-binding cassette (ABC) transporters and anti-apoptotic molecules, active DNA-repair, slow replication capacities and they produce growth factors that confer refractoriness to antineoplastic treatments. The inefficacy of conventional therapies towards the stem cell population might explain cancer chemoresistance and the high frequency of relapse shown by the majority of tumors. Nowadays, in fact all the therapies available are not sufficient to cure patients with advanced forms of colon cancer since they target differentiated cancer cells which constitute most of the tumor mass and spare CSCs. Since CSCs are the entities responsible for the development of the tumor and represent the only cell population able to sustain tumor growth and progression, these cells represent the elective target for innovative therapies. PMID- 24212792 TI - Essential gene pathways for glioblastoma stem cells: clinical implications for prevention of tumor recurrence. AB - Glioblastoma (World Health Organization/WHO grade IV) is the most common and most aggressive adult glial tumor. Patients with glioblastoma, despite being treated with gross total resection and post-operative radiation/chemotherapy, will almost always develop tumor recurrence. Glioblastoma stem cells (GSC), a minor subpopulation within the tumor mass, have been recently characterized as tumor initiating cells and hypothesized to be responsible for post-treatment recurrence because of their enhanced radio-/chemo-resistant phenotype and ability to reconstitute tumors in mouse brains. Genome-wide expression profile analysis uncovered molecular properties of GSC distinct from their differentiated, proliferative progeny that comprise the majority of the tumor mass. In contrast to the hyperproliferative and hyperangiogenic phenotype of glioblastoma tumors, GSC possess neuroectodermal properties and express genes associated with neural stem cells, radial glial cells, and neural crest cells, as well as portray a migratory, quiescent, and undifferentiated phenotype. Thus, cell cycle-targeted radio-chemotherapy, which aims to kill fast-growing tumor cells, may not completely eliminate glioblastoma tumors. To prevent tumor recurrence, a strategy targeting essential gene pathways of GSC must be identified and incorporated into the standard treatment regimen. Identifying intrinsic and extrinsic cues by which GSC maintain stemness properties and sustain both tumorigenesis and anti apoptotic features may provide new insights into potentially curative strategies for treating brain cancers. PMID- 24212793 TI - Common altered epigenomic domains in cancer cells: characterization and subtle variations. AB - We have previously identified large megabase-sized hypomethylated zones in the genome of the breast cancer cell line MCF-7 using the TspRI-ExoIII technique. In this report, we used a more convenient high throughput method for mapping the hypomethylated zones in a number of human tumor genomes simultaneously. The method was validated by the bisulfite sequencing of 39 randomly chosen sites in a demethylated domain and by bisulfite genome-wide sequencing of the MCF-7 genome. This showed that the genomes of the various tumor cell lines, as well as some primary tumors, exhibit common hypomethylated domains. Interestingly, these hypomethylated domains are correlated with low CpG density distribution genome wide, together with the histone H3K27Me3 landscape. Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells. Treatment with drugs resulted in en-bloc changes to the methylation domains. A close examination of the methylation domains found differences between non-invasive and invasive tumors with respect to tumorigenesis related genes. Taken together these results suggest that the human genome is organized in epigenomic domains that contain various different types of genes and imply that there are cis- and trans-regulators that control these domain-wide epigenetic changes and hence gene expression in the human genome. The hypomethylated domains are located in gene deserts that contain mainly tissue-specific genes and therefore we hypothesize that tumor cells keep these regions demethylated and silenced in order to save energy and resources and allow higher levels of cell proliferation and better survival (a thrifty tumor genome hypothesis). PMID- 24212794 TI - EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects. AB - Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease. PMID- 24212795 TI - Glioma Specific Extracellular Missense Mutations in the First Cysteine Rich Region of Epidermal Growth Factor Receptor (EGFR) Initiate Ligand Independent Activation. AB - The epidermal growth factor receptor (EGFR) is overexpressed or mutated in glioma. Recently, a series of missense mutations in the extracellular domain (ECD) of EGFR were reported in glioma patients. Some of these mutations clustered within a cysteine-rich region of the EGFR targeted by the therapeutic antibody mAb806. This region is only exposed when EGFR activates and appears to locally misfold during activation. We expressed two of these mutations (R324L and E330K) in NR6 mouse fibroblasts, as they do not express any EGFR-related receptors. Both mutants were autophosphorylated in the absence of ligand and enhanced cell survival and anchorage-independent and xenograft growth. The ECD truncation that produces the de2-7EGFR (or EGFRvIII), the most common EGFR mutation in glioma, generates a free cysteine in this same region. Using a technique optimized for detecting disulfide-bonded dimers, we definitively demonstrated that the de2 7EGFR is robustly dimerized and that ablation of the free cysteine prevents dimerization and activation. Modeling of the R324L mutation suggests it may cause transient breaking of disulfide bonds, leading to similar disulfide-bonded dimers as seen for the de2-7EGFR. These ECD mutations confirm that the cysteine-rich region of EGFR around the mAb806 epitope has a significant role in receptor activation. PMID- 24212799 TI - Inferences for the Lead Time in Breast Cancer Screening Trials under a Stable Disease Model. AB - We estimated the effects on the lead time for women participating in a long-term breast cancer screening program when the screening sensitivities and disease progression are independent of age. The lead time, or time by which a diagnosis is advanced by screening, is one of the major concerns of any cancer screening program, which we consider to include both a mammogram and physical examination. Using estimates of test sensitivities and mean sojourn times previously calculated by other authors from observed data, we estimated properties of the lead time. We utilized the model for the lead time derived by other authors and ran simulations for different screening program designs, concentrating on screening interval lengths of 0.5 years, 1 year, 1.5 years, and 2 years. These estimates were based on a long-term screening program from age 50 to 80. For each six-month decrease in screening interval length, we estimated the percent increase in mean lead time, as well as the percent increase in the proportion of clinical patients who will have their cancer detected at a screening exam. PMID- 24212797 TI - Prognostic value of colorectal cancer biomarkers. AB - Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC. PMID- 24212796 TI - Wnt/beta-catenin Signaling in Normal and Cancer Stem Cells. AB - The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, beta-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/beta catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling. PMID- 24212798 TI - Cancer stem cells and side population cells in breast cancer and metastasis. AB - In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis. PMID- 24212801 TI - The role of tumour stroma in colorectal cancer invasion and metastasis. AB - Colorectal cancer (CRC) is a major cause of mortality in western society with a 5 year survival of approximately 50%. Metastasis to the liver and lungs is the principal cause of death and occurs in up to 25% of patients at presentation. Despite advances in available techniques for treating metastases, the majority of patients remain incurable and existing adjuvant therapies such as chemotherapy are only of limited effectiveness. Understanding the molecular mechanisms underlying the metastatic process may allow us to identify those at greatest risk of recurrence and discover new tumour targets to prevent disease progression. It is now apparent that tumour stroma plays an important role in promoting tumour progression. A pronounced desmoplastic reaction was associated with a reduced immune response and has been shown to be an independent poor prognostic indicator in CRC and cancer recurrence. Determining the cause(s) and effect(s) of this stromal response will further our understanding of tumour cell/stromal interactions, and will help us identify prognostic indicators for patients with CRC. This will not only allow us to target our existing treatments more effectively, we also aim to identify novel and more specific therapeutic targets for the treatment of CRC which will add to our current therapeutic options. PMID- 24212800 TI - Lymph node metastasis of gastric cancer. AB - Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer. PMID- 24212802 TI - X inactivation and progenitor cancer cells. AB - In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing. PMID- 24212803 TI - Predictive factors of the response of rectal cancer to neoadjuvant radiochemotherapy. AB - Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: "rectal", "predictive", "radiochemotherapy", "neoadjuvant", "response" and "biomarkers". Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing interesting results that might lead to the identification of new useful biomarkers. Evaluation of biomarkers in larger, prospective trials are required to guide therapeutic strategies. PMID- 24212805 TI - Cell Autonomous and Non-Autonomous Functions of IKKbeta and NF-kappaB during the Pathogenesis of Gastrointestinal Tumors. AB - Genetic studies describing a link between cancer and inflammation have increased recently. Activation of the transcription factor nuclear factor-kappaB (NF kappaB) and its effector pathways has been proposed to be the missing link between these two processes. NF-kappaB is persistently activated in several types of tumors. However, NF-kappaB has a distinct role in cancer cells and in inflammatory cells. While in tumor cells NF-kappaB controls cell survival, in inflammatory cells NF-kappaB activates genes that encode pro-inflammatory cytokines which further act in a paracrine manner within the tumor microenvironment to contribute to tumorigenesis. Inactivation of NF-kappaB can also reduce chemoresistance and radioresistance of cancer cells. Therefore, specific NF-kappaB inhibition in combination with cytotoxic drugs and/or irradiation represents a very promising strategy for cancer therapy. PMID- 24212804 TI - Harnessing dendritic cells for tumor antigen presentation. AB - Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8+ and CD4+ T cells; the in vitro loading of DCs with tumor antigens. PMID- 24212806 TI - Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell based immunotherapy and intensity-modulated radiotherapy. AB - Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies. PMID- 24212807 TI - Targeted therapy for biliary tract cancer. AB - It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important. PMID- 24212809 TI - Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs) In Vitro. AB - Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs). Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium (MTS), we found that the IC50 for inhibition of proliferation is 15.3 +/- 4.1 uM for SUM-149 and 24.3 +/- 2.1 uM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 uM for SUM-149 and around 2 uM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH) positive population in SUM-159 by 45% +/- 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs. PMID- 24212808 TI - Targeted therapy in nonmelanoma skin cancers. AB - Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC. PMID- 24212810 TI - Neoadjuvant therapy in patients with pancreatic cancer: a disappointing therapeutic approach? AB - Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed. PMID- 24212811 TI - The Role of High Frequency Dynamic Threshold (HiDT) Serum Carcinoembryonic Antigen (CEA) Measurements in Colorectal Cancer Surveillance: A (Revisited) Hypothesis Paper. AB - Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands. PMID- 24212812 TI - Different aspects of self-reported quality of life in 450 german melanoma survivors. AB - The present study was aimed at assessing quality of life (QoL) in a total of 450 melanoma patients who filled out the EORTC QLQ-C30 (Q1; 15 months post diagnosis) as part of the OVIS Study. Follow-up questionnaires (Q2) were administered two years after Q1. The analyses presented herein were based on the following assumptions: QoL of melanoma patients is worse than that of a German reference population. Further, both tumor location and tumor stage have an influence on self-reported QoL, with patients with tumors located on face, head, neck, and advanced tumor stage (T3/T4) reporting the worst QoL levels. Finally, patients' QoL improves over time based on the theory of disease adaptation. In contrast to the above assumptions, with the exception of global health/QoL scores, differences between OVIS and the reference population were below the minimal clinical important difference of ten points. Furthermore, no clinically meaningful differences were found between patients after stratifying our data by tumor location and tumor stage. Finally, no clinically relevant changes were seen between Q1 and Q2 across all scales of the EORTC QLQ-C30. However, when data were stratified by patients with stable disease versus those with progression, clinically relevant differences were found between Q1 and Q2 predominantly in women in the latter group regarding emotional function, insomnia, dyspnoea, and fatigue. The lack of clinically meaningful differences across strata (tumor location; tumor stage), time, and patients compared to a reference population is surprising. However, it is possible that the instrument used, a generic QoL instrument, is generally not sensitive enough to detect differences in melanoma patients. Our findings may further be explained by the fact that all patients included in our sample had been diagnosed well before Q1, i.e., main illness adaptation processes may have occurred before study entry. PMID- 24212814 TI - Systematic review of breast cancer biology in developing countries (part 1): Africa, the middle East, eastern europe, Mexico, the Caribbean and South america. AB - There has been no systematic appraisal of ethnicity-based variations in breast cancer (BC) biology amongst women from developing countries. A qualitative systematic review was conducted of breast cancer size, stage, grade, histological type, extra-mammary involvement, hormone receptor status as well as patient demographics. This review includes patients from Africa, the Middle East, Eastern Europe, Mexico, the Caribbean and South America. BC in these regions present at an earlier age with large aggressive tumours. Distant metastases are frequently present at the time of diagnosis. African women have a higher frequency of triple negative tumours. Over half of Middle Eastern women have lymph node involvement at the time of diagnosis. Despite experiencing a lower incidence compared to the Ashkenazi Jewish population, Palestinian women have poorer five-year survival outcomes. The majority of women from Mexico and South America have stage two or three disease whilst over sixty percent of women from Eastern Europe have either stage one or stage two disease. The biological characteristics of BC in the Caribbean cannot be fully assessed due to a paucity of data from the region. BC amongst the developing world is characterised by an early peak age of onset with aggressive biological characteristics. Strategies that improve breast cancer awareness, address amenable risk factors and improve early detection are essential. PMID- 24212813 TI - Tomato lycopene and lung cancer prevention: from experimental to human studies. AB - Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk. PMID- 24212815 TI - Systematic review of breast cancer biology in developing countries (part 2): asian subcontinent and South East Asia. AB - There has been no systematic appraisal of ethnicity-based variations in breast cancer (BC) biology amongst women from developing countries. A qualitative systematic review was conducted of breast cancer size, stage, grade, histological type, extra-mammary involvement, hormone receptor status as well as patient demographics. This review includes patients from Africa, the Middle East, Eastern Europe, Mexico, the Caribbean and South America. BC in these regions present at an earlier age with large aggressive tumours. Distant metastases are frequently present at the time of diagnosis. African women have a higher frequency of triple negative tumours. Over half of Middle Eastern women have lymph node involvement at the time of diagnosis. Despite experiencing a lower incidence compared to the Ashkenazi Jewish population, Palestinian women have poorer five-year survival outcomes. The majority of women from Mexico and South America have stage two or three disease whilst over sixty percent of women from Eastern Europe have either stage one or stage two disease. The biological characteristics of BC in the Caribbean cannot be fully assessed due to a paucity of data from the region. BC amongst the developing world is characterised by an early peak age of onset with aggressive biological characteristics. Strategies that improve breast cancer awareness, address amenable risk factors and improve early detection are essential. PMID- 24212817 TI - Comparison of dose response models for predicting normal tissue complications from cancer radiotherapy: application in rat spinal cord. AB - Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the chi2-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint. PMID- 24212816 TI - Differentiation therapy of acute myeloid leukemia. AB - Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called 'differentiation therapy', was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25 dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML. PMID- 24212818 TI - Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer. AB - Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a "signaling hub" where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment. PMID- 24212819 TI - Roles of StearoylCoA Desaturase-1 in the Regulation of Cancer Cell Growth, Survival and Tumorigenesis. AB - The development and maintenance of defining features of cancer, such as unremitting cell proliferation, evasion of programmed cell death, and the capacity for colonizing local tissues and distant organs, demand a massive production of structural, signaling and energy-storing lipid biomolecules of appropriate fatty acid composition. Due to constitutive activation of fatty acid biosynthesis, cancer cell lipids are enriched with saturated (SFA) and, in particular, monounsaturated fatty acids (MUFA), which are generated by StearoylCoA desaturase-1, the main enzyme that transforms SFA into MUFA. An increasing number of experimental and epidemiological studies suggest that high levels of SCD1 activity is a major factor in establishing the biochemical and metabolic perturbations that favors the oncogenic process. This review examines evidence that suggests the critical implication of SCD1 in the modulation of multiple biological mechanisms, specifically lipid biosynthesis and proliferation and survival signaling pathways that contribute to the development and progression of cancer. PMID- 24212820 TI - Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives. AB - Over the last decade, extensive studies have been made to understand the role played by the mammalian target of rapamycin (mTOR) in cancer. Knowledge in this field has been gained from discoveries in basic research as well as from observations made in patients treated with allosteric mTOR inhibitors such as rapamycin. Despite promising preclinical studies, targeting mTOR in cancer therapy has shown limited clinical benefits so far. However, recent findings have revealed the complexity of the functions of mTOR in cancer and have helped develop new strategies to improve the anticancer efficacy of mTOR inhibitors. In particular, a complex network between mTOR and other signaling pathways has been identified that influences the anticancer efficacy of mTOR inhibitors. In addition, an emerging role of mTOR in the tumor microenvironment has been suggested. In this review, we confront the major findings that have been made in the past, both in experimental settings as well as in clinical trials. We further review the strategies that have been designed to further improve the efficacy of therapies targeting mTOR. PMID- 24212821 TI - Activation of PDGFr-beta Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer. AB - Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-beta/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-beta with imatinib activates human PDGFr-beta/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment- and time-dependent. Soon after treatment, levels of human PDGFr-beta, compared to untreated tumors, are 3.4*, 12.4*, and 5.7* higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-beta and phosphorylated PDGFr-beta by 5.3* and 4*, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy. PMID- 24212822 TI - Tumor cell seeding during surgery-possible contribution to metastasis formations. AB - In spite of optimal local control in breast cancer, distant metastases can develop as a systemic part of this disease. Surgery is suspected to contribute to metastasis formation activating dormant tumor cells. Here we add data that seeding of cells during surgery may add to the risk of metastasis formation. The change in circulating epithelial tumor cells (CETC) was monitored in 66 breast cancer patients operated on with breast conserving surgery or mastectomy and during the further course of the disease, analyzing CETC from unseparated white blood cells stained with FITC-anti-EpCAM. An increase in cell numbers lasting until the start of chemotherapy was observed in about one third of patients. It was more preeminent in patients with low numbers of CETC before surgery and, surprisingly, in patients without involved lymph nodes. Patients with the previously reported behavior-Reincrease in cell numbers during adjuvant chemotherapy and subsequent further increase during maintenance therapy-were at increased risk of relapse. In addition to tumor cells already released during growth of the tumor, cell seeding during surgery may contribute to the early peak of relapses observed after removal of the primary tumor and chemotherapy may only marginally postpone relapse in patients with aggressively growing tumors. PMID- 24212824 TI - Enhancing photodynamyc therapy efficacy by combination therapy: dated, current and oncoming strategies. AB - Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors. PMID- 24212823 TI - State of the art in tumor antigen and biomarker discovery. AB - Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including "omics" technology. PMID- 24212826 TI - The role of epidermal growth factor receptor mutations and epidermal growth factor receptor-tyrosine kinase inhibitors in the treatment of lung cancer. AB - Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8-9 months and a one-year survival of 30%-40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects. PMID- 24212827 TI - Metastasizing, Luciferase Transduced MAT-Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug. AB - The most fatal outcomes of prostate carcinoma (PCa) result from hormone refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented. PMID- 24212825 TI - Regulation of autophagy by kinases. AB - Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID- 24212828 TI - Clinical trial design for testing the stem cell model for the prevention and treatment of cancer. AB - The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in "complete" or "partial" responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples. PMID- 24212829 TI - Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects. AB - The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1) cell cycle S-phase/G2-phase arrest; (2) prevention of cyclin inhibitor degradation; (3) protection of p53 from inactivation by phosphorylation; and (4) blockage of K+ ion channels opened by estradiol and epidermal growth factor (EGF). The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1) tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2) Herceptin antibody resistance and cardiac (arrest) arrhythmias; and (3) doxorubicin's bystander cell toxicity. PMID- 24212830 TI - TRAF4, at the Crossroad between Morphogenesis and Cancer. AB - Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production. PMID- 24212831 TI - Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis. AB - Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis. PMID- 24212833 TI - A theoretical approach on controlling agricultural pest by biological controls. AB - In this paper we propose and analyze a prey-predator type dynamical system for pest control where prey population is treated as the pest. We consider two classes for the pest namely susceptible pest and infected pest and the predator population is the natural enemy of the pest. We also consider average delay for both the predation rate i.e. predation to the susceptible pest and infected pest. Considering a subsystem of original system in the absence of infection, we analyze the existence of all possible non-negative equilibria and their stability criteria for both the subsystem as well as the original system. We present the conditions for transcritical bifurcation and Hopf bifurcation in the disease free system. The theoretical evaluations are demonstrated through numerical simulations. PMID- 24212834 TI - Anteroposterior displacement behavior of the center of pressure, without visual reference, in postmenopausal women with and without lumbar osteoporosis. AB - OBJECTIVE: The aims of this study were to evaluate the anteroposterior displacement behavior of the center of pressure without any visual reference and determine its relationship with knee muscle strength and reports of falls in postmenopausal women. Among those with osteoporosis, the specific objective was to evaluate the correlation of thoracic kyphosis and vitamin D with center of pressure displacement. METHODS: This was a cross-sectional observational study without intervention. The assessments were performed on 126 postmenopausal women (aged 55-65 years) who were grouped according to their lumbar bone density into osteoporosis and control groups. Center of pressure was evaluated on a force platform (100 Hz frequency and 10 Hz filter), with the subjects standing on both feet with eyes closed for 60 seconds. Knee muscle strength was evaluated using an isokinetic dynamometer in concentric/concentric mode at a velocity of 60 degrees /s. In the osteoporosis group, vitamin D was assayed, and the thoracic spine was radiographed. RESULTS: In the control group, there was a correlation between the center of pressure and knee strength (r = 0.37; p<0.003). Reports of falls were not associated with center of pressure displacement (p = 0.056). In the osteoporosis group, thoracic kyphosis and vitamin D levels were not correlated with the center of pressure. CONCLUSION: Anteroposterior center of pressure displacement without visual influence was not associated with falls, thoracic kyphosis or vitamin D in the osteoporosis group. Only knee muscle strength was associated with center of pressure displacement in the control group. PMID- 24212835 TI - Evaluation of the traditional and revised World Health Organization classifications of dengue cases in Brazil. AB - OBJECTIVE: Dengue is a worldwide public health problem with approximately 50 million cases reported annually. The World Health Organization proposed a revised classification system in 2008 to more effectively identify the patients who are at increased risk of complications from dengue. Few studies have validated this new classification system in clinical practice. We conducted a cross-sectional study of patients hospitalized for dengue in Dourados, Mato Grosso do Sul, Brazil, to evaluate the capacity of the two classification systems for detecting severe cases of dengue. MATERIALS AND METHODS: We conducted a cross-sectional study of survey data from the medical records of patients admitted to the University Hospital of the Federal University of Grande Dourados under clinical suspicion of dengue during an epidemic from September 2009 to April 2010. RESULTS: The distribution of patients according to the traditional classification system was as follows: dengue fever, 150/181 (82.9%); dengue hemorrhagic fever, 27/181 (14.9%); and dengue hemorrhagic shock, 4/181 (2.2%). Using the revised classification system, the distribution was as follows: dengue without warning signs, 45/181 (24.3%); dengue with warning signs, 107/181 (59.1%); and severe dengue, 29/181 (15.6%). Of the 150 patients classified as having dengue fever, 105 (70%) were reclassified as having dengue with warning signs or severe dengue. CONCLUSION: These data demonstrate that the revised classification system has greater discriminatory power for detecting patients at risk of progression to severe disease and those needing hospitalization. PMID- 24212832 TI - Review of histopathological and molecular prognostic features in colorectal cancer. AB - Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer. PMID- 24212836 TI - Duration effect of desflurane anesthesia and its awakening time and arterial concentration in gynecologic patients. AB - OBJECTIVES: To determine the awakening arterial blood concentration of desflurane and its relationship with the end-tidal concentration during emergence from various durations of general anesthesia. METHOD: In total, 42 American Society of Anesthesiologists physical status class I-II female patients undergoing elective gynecologic surgery were enrolled. General anesthesia was maintained with fixed 6% inspiratory desflurane in 6 l min-1 oxygen until shutoff of the vaporizer at the end of surgery. One milliliter of arterial blood was obtained for desflurane concentration determination by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after the discontinuation of desflurane and at the time of eye opening upon verbal command, defined as awakening. Concentrations of inspiratory and end-tidal desflurane were simultaneously detected by an infrared analyzer. RESULTS: The mean arterial blood concentration of desflurane was 1.20% at awakening, which correlated with the awakening end-tidal concentration of 0.96%. The mean time from the discontinuation of desflurane to eye opening was 5.2 minutes (SD = 1.6, range 3-10), which was not associated with the duration of anesthesia (60-256 minutes), total fentanyl dose, or body mass index (BMI). CONCLUSIONS: The mean awakening arterial blood concentration of desflurane was 1.20%. The time to awakening was independent of anesthetic duration within four hours. Using well-assisted ventilation, the end-tidal concentration of desflurane was proven to represent the arterial blood concentration during elimination and could be a clinically feasible predictor of emergence from general anesthesia. PMID- 24212837 TI - Radiofrequency ablation can reverse the structural remodeling caused by frequent premature ventricular contractions originating from the right ventricular outflow tract even in a "normal heart". AB - OBJECTIVE: The aim of this study was to evaluate whether frequent premature ventricular contractions originating from the right ventricular outflow tract remodel the cardiac structure and function in patients with a "seemingly normal heart" and whether radiofrequency ablation can reverse this remodeling. METHODS: Sixty-eight patients with idiopathic frequent premature ventricular contractions originating from the right ventricular outflow tract and normal heart structure and function were enrolled in this study. The patients were divided into three groups according to the therapeutic method: radiofrequency ablation group (24 cases), anti-arrhythmia drug group (26 cases), and control group (18 cases without any treatment). Clinical Registration number: ChiCTR-ONRC-12002834 RESULTS: The basic patient characteristics were comparable between the three groups, except for the premature ventricular contraction rate, which was significantly lower in the control group. After six months of follow up, the premature ventricular contraction rate was significantly reduced in the radiofrequency ablation group, which was accompanied by a significant decrease in the following cardiac cavity inner diameters, as determined by echocardiography: right atrium (33.33+/-3.78 vs. 30.05+/-2.60 mm, p = 0.001), right ventricle (23.24+/-2.40 vs. 21.05+/-2.16 mm, p = 0.020), and left ventricle (44.76+/-4.33 vs. 41.71+/-3.44 mm, p = 0.025). These results were similar in the anti arrhythmia drug group, although this group exhibited a smaller extent of change (right atrium: 33.94+/-3.25 vs. 31.27+/-3.11 mm, p = 0.024; right ventricle: 22.97+/-3.09 vs. 21.64+/-2.33 mm, p = 0.049; left ventricle: 45.92+/-6.38 vs. 43.84+/-5.67 mm, p = 0.039), but not in the control group (p>0.05). There was a tendency toward improvement in the cardiac functions in both the radiofrequency ablation and anti-arrhythmia drug groups. However, these differences were not statistically significant (p>0.05). CONCLUSIONS: These results indicate that radiofrequency ablation can potentially reverse the cardiac remodeling caused by frequent premature ventricular contractions even in structurally normal hearts and that frequent premature ventricular contractions should be abated even in structurally normal hearts. PMID- 24212838 TI - Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial. AB - OBJECTIVES: To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate METHODS: A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer's test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872 RESULTS: All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer's test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression. CONCLUSIONS: All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment. PMID- 24212839 TI - Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B. AB - OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had >=3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone. PMID- 24212840 TI - Early assessment of percutaneous coronary interventions for chronic total occlusions analyzed by novel echocardiographic techniques. AB - OBJECTIVE: Successful revascularization of chronic total occlusions has been associated with improved left ventricular systolic function, reduced anginal symptoms, increased exercise capacity, and increased survival. This study was conducted to determine the impact of revascularization in chronic total occlusion on left ventricular function using novel echocardiographic techniques. METHODS: A total of 129 patients with chronic total occlusion who underwent revascularization between April 2011 and November 2012 were included in this study. Echocardiographic assessments with two-dimensional speckle tracking echocardiography and real-time three-dimensional echocardiography were performed before the procedure and one month after the procedure. The left ventricular ejection fraction, left ventricular volumes, and three-dimensional systolic dyssynchrony index were quantified. RESULTS: An immediate procedural success was obtained in 118 patients (91.5%). There were no acute or subacute stent thromboses during follow-up. The mean left ventricular ejection fraction significantly increased (p<0.001), while the left ventricular end-diastolic and end-systolic volumes significantly decreased (p = 0.001 and p<0.001, respectively). The three-dimensional systolic dyssynchrony index also decreased significantly (p<0.001). The global longitudinal strain showed a significant increase after successful revascularization (p<0.001). An increase in the global longitudinal strain was correlated with an increase in the left ventricular ejection fraction (r = 0.27, p = 0.02). The patients with a left ventricular ejection fraction >=50% displayed a greater improvement in the global longitudinal strain, and the patients with diabetes showed less improvement. CONCLUSIONS: Using novel echocardiographic techniques, our results showed that restoring the coronary blood flow in chronic total occlusion patients reduces the left ventricular volumes and improves the left ventricular ejection fraction and the global longitudinal strain of hibernating myocardium. PMID- 24212841 TI - Tocotrienol supplementation in postmenopausal osteoporosis: evidence from a laboratory study. AB - OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model. MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker). RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level. CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women. PMID- 24212842 TI - Periostin as a modulator of chronic cardiac remodeling after myocardial infarction. AB - OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means+/-SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats. PMID- 24212843 TI - Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin induced sclerotic mice. AB - OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 MUM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of alpha-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1. PMID- 24212844 TI - The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR 2) against red blood cell membrane oxidative stress in rats with streptozotocin induced diabetes. AB - OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients. PMID- 24212845 TI - Effects of different types of auditory temporal training on language skills: a systematic review. AB - Previous studies have investigated the effects of auditory temporal training on language disorders. Recently, the effects of new approaches, such as musical training and the use of software, have also been considered. To investigate the effects of different auditory temporal training approaches on language skills, we reviewed the available literature on musical training, the use of software and formal auditory training by searching the SciELO, MEDLINE, LILACS-BIREME and EMBASE databases. STUDY DESIGN: Systematic review. RESULTS: Using evidence levels I and II as the criteria, 29 of the 523 papers found were deemed relevant to one of the topics (use of software - 13 papers; formal auditory training - six papers; and musical training - 10 papers). Of the three approaches, studies that investigated the use of software and musical training had the highest levels of evidence; however, these studies also raised concerns about the hypothesized relationship between auditory temporal processing and language. Future studies are necessary to investigate the actual contribution of these three types of auditory temporal training to language skills. PMID- 24212846 TI - PTK2 and PTPN11 expression in myelodysplastic syndromes. AB - OBJECTIVE: The aim of this study was to evaluate the expression of protein tyrosine kinase 2 and protein tyrosine phosphatase non-receptor type 11, which respectively encode focal adhesion kinase protein and src homology 2 domain containing protein-tyrosine phosphatase 2, in hematopoietic cells from patients with myelodysplastic syndromes. METHODS: Protein tyrosine kinase 2 and tyrosine phosphatase non-receptor type 11 expressions were analyzed by quantitative polymerase chain reaction in bone marrow cells from patients with myelodysplastic syndromes and healthy donors. RESULTS: Protein tyrosine kinase 2 and tyrosine phosphatase non-receptor type 11 expressions did not significantly differ between normal cells and myelodysplastic cells. CONCLUSIONS: Our data suggest that despite the relevance of focal adhesion kinase and src homology 2 domain containing protein-tyrosine phosphatase 2 in hematopoietic disorders, their mRNA expression do not significantly differ between total bone marrow cells from patients with myelodysplastic syndromes and healthy donors. PMID- 24212847 TI - Early transconjunctival needling revision with 5-fluorouracil versus medical treatment in encapsulated blebs: a 12-month prospective study. AB - OBJECTIVE: To compare the efficacy of transconjunctival needling revision with 5 fluorouracil versus medical treatment in glaucomatous eyes with uncontrolled intraocular pressure due to encapsulated bleb after trabeculectomy. METHODS: Prospective, randomized, interventional study. A total of 40 eyes in 39 patients with elevated intraocular pressure and encapsulated blebs diagnosed at a maximum five months after primary trabeculectomy with mitomycin C were included. The eyes were randomized to either transconjunctival needling revision with 5- fluorouracil or medical treatment (hypotensive eyedrops). A maximum of two transconjunctival needling revisions per patient was allowed in the needling arm. All patients underwent follow-up for 12 months. Successful treatment was defined as an intraocular pressure <= 18 mmHg and a 20% reduction from baseline at the final follow-up. Clinicaltrial.gov: NCT01887223. RESULTS: Mean intraocular pressure at the final 12-month follow-up was lower in the transconjunctival needling revision group compared to the medical treatment group. Similar numbers of eyes reached the criteria for treatment success in both the transconjunctival needling revision group and the medical treatment group. CONCLUSIONS: Despite similar success rates in eyes randomized to transconjunctival needling revision with 5-fluorouracil compared to eyes receiving medical treatment, there was a significantly lower mean intraocular pressure at 12 months after transconjunctival needling revision. PMID- 24212848 TI - Electrocardiographic data should be coupled with tissue-Doppler imaging and clinical follow-up evaluation to determine cardiac involvement in lichen planus. PMID- 24212849 TI - Retraction. An overview of recently published medical papers in Brazilian scientific journals. PMID- 24212850 TI - Retraction. A survey of recently published cardiovascular, hematological and pneumological original articles in the Brazilian scientific press. PMID- 24212851 TI - Chromosomal location of the genes for ferredoxin in wheat, barley and rye. PMID- 24212852 TI - Chromosomal location in wheat of the genes coding for the acyl carrier proteins I and III. PMID- 24212853 TI - Analysis of cytoplasmic genomes in somatic hybrids between navel orange (Citrus sinensis Osb.) and 'Murcott' tangor. AB - Somatic hybrid plants were produced by protoplast fusion of navel orange and 'Murcott' tangor. Hybridity of the plants was confirmed by the restriction endonuclease analysis of nuclear ribosomal DNA. All of the plants (16 clones) were normal, uniform, and had the amphidiploid chromosome number of 36 (2n=2x=18 for each parent). The cpDNA analysis showed that each of the 16 somatic hybrids contained either one parental chloroplast genome or the other. In all cases, the mitochondrial genomes of the regenerated somatic hybrids were of the navel orange type. PMID- 24212854 TI - Molecular characterization of mitochondrial DNA of different subtypes of male sterile cytoplasms of the sugar beet Beta vulgaris L. AB - Mitochondrial (mt) DNA from eight cytoplasmic male-sterile (cms) lines of sugar beet from different breeding stations was investigated by restriction fragment analysis and Southern hybridization. All cms lines showed similar but not identical restriction and hybridization signal patterns, readily distinguishable from those of fertile (N) cytoplasm. Digestion of the mtDNA with BamHI, EcoRI, SalI, and XhoI revealed distinct differences between the sterile lines, and six subtypes of the S cytoplasm could be distinguished. Differences between the sterile lines were confirmed by hybridization with a [Formula: see text] gene probe revealing minor, line-specific hybridization signals. The data presented provide evidence for the existence of considerable variation within the only commercially used source of cms in the sugar beet, the Owen's type of cytoplasm. PMID- 24212855 TI - Correlation between testcross performance of lines at early and late selfing generations. AB - In hybrid breeding programs, testcross evaluation of lines can be done during the early stages of selfing (early testing) or delayed until the lines are near homozygous. To evaluate the usefulness of early testing, the expected genetic and phenotypic correlations between testcross performance at different selfing generations were examined. The genetic correlation (r GnGn' ) between testcross performance of S n and S n' , (n'>n) individuals or lines is equal to the square root of the ratio of their testcross genetic variances, and it is a function of the inbreeding coefficients (F) at the two selfing generations, i.e., r GnGn'=[(1+F n )/(1+F n )](0.5). The genetic correlation between testcross performance of lines and their directly descended homozygous (n'=infinity) lines is 0.71 for S1; 0.87 for S2, 0.93 for S3, 0.97 for S4, 0.98 for S5, and 0.99 for S5 lines. The effectiveness of early testing is limited mainly by nongenetic effects. The square root of testcross heritability at generation n sets the upper limit on the correlation between phenotypic value at generation n and genotypic value at homozygosity. The probabilities of correctly retaining S n individuals or lines that have superior testcross performance at homozygosity (n'=infinity) indicate that early testing should be effective in identifying lines with above- and below-average combining ability. However, the risk of losing lines with superior combining ability is high if strong (best 10%) selection pressure is applied during early testing. If only a small proportion of lines is retained based on testcross performance and/or if the heritability of the trait is low, selfing for two or three generations prior to testcrossing may be desirable to increase the likelihood of retaining lines that perform well at homozygosity. The theoretical results in this study support the testcross evaluation procedures for grain yield used by most maize (Zea mays L.) breeders. PMID- 24212856 TI - RFLP mapping of I1, a new locus in tomato conferring resistance against Fusarium oxysporum f. sp. lycopersici race 1. AB - The inheritance and linkage relationships of a gene for resistance to Fusarium oxysporum f. sp. lycopersici race 1 were analyzed. An interspecific hybrid between a resistant Lycopersicon pennellii and a susceptible L. esculentum was backcrossed to L. esculentum. The genotype of each backcross-1 (BC1) plant with respect to its Fusarium response was determined by means of backcross-2 progeny tests. Resistance was controlled by a single dominant gene, I1, which was not allelic to I, the traditional gene for resistance against the same fungal pathogen that was derived from L. pimpinellifolium. Linkage analysis of 154 molecular markers that segregated in the BC1 population placed I1 between the RFLP markers TG20 and TG128 on chromosome 7. The flanking markers were used to verify the assignment of the I1 genotype in the segregating population. The results are discussed with reference to the possibility of cloning Fusarium resistance genes in tomato. PMID- 24212857 TI - Biochemical evidence of a translocation between 6 RL/7 RL chromosome arms in rye (Secale cereale L.). A genetic map of 6R chromosome. AB - The segregation of different isozymic loci was investigated in backcrosses and F2s in rye. The leucin aminopeptidase-1 (Lap-1), Aconitase-1 (Aco-1), Esterase-6 (Est-6), Esterase-8 (Est-8), and Endopeptidase-1 (Ep-1) loci were linked. The Aco 1, Est-6, and Est-8 loci have been previously located on the 6RL chromosome arm. The Lap-1 locus has been located on the 6RS chromosome arm. The results favor the gene order: Lap-1... (centromere)... Aco-1... Est-8... Est-6... Ep-1. The isoelectric focusing separations of aqueous extracts from mature embryo tissue of wheat-rye addition and substitution lines involving the chromosomes of cereal rye Secale cereale L. confirmed the gene location of locus Ep-1 on the 6RL chromosome arm. Screening of wheat-rye addition lines involving the chromosomes of Secale montanum revealed that Ep-1 locus is not located on chromosome 6R of S. montanum. These results are the first biochemical evidence of the translocation between chromosome arms 6RL/7RL in the evolution of S. cereale from S. montanum. PMID- 24212858 TI - Genetic control of Lucilia cuprina: analysis of field trial data using simulation techniques. AB - An analytical version of the genetic control simulation program GENCON has been used to further analyze the data obtained during field trials of genetic control of the sheep blowfly, Lucilia cuprina, in 1976-79. In the simulations, population trends from a nonrelease area were used as an estimate of the rates of increase that would have occurred in the target population if there had been no releases. Genetic data from the target area (frequencies of matings by released males) were used to predict the frequencies of descendants of released males, the resulting genetic death, and the effects of this on population trends. In simulations that assumed no migration and full survival and competitiveness of all field-reared descendants of released males (translocation-bearing males and males and females heterozygous for deleterious mutations), neither the predicted genetic changes nor the predicted population trends agreed well with the observed data. Further simulations suggested that reduced survival or competitiveness of field-reared descendants did not account for this disagreement, but that immigration of wild flies into the test areas was probably a major contributor to the failure to achieve suppression. However, immigration alone was not sufficient to explain all the differences between observed and expected results. Other plausible contributors to this failure were: (1) lower survival of translocation males due to the effects of a dieldrin resistance allele carried on the translocation, and (2) increased survival of immature stages of L. cuprina at low population densities. PMID- 24212859 TI - Chromosomal control of wheat gliadin protein epitopes: analysis with specific monoclonal antibodies. AB - The genetic relationships between small clusters of monomeric alcohol-soluble wheat (Triticum aestivum L.) grain storage proteins (gliadins) were studied using a panel of monoclonal antibodies and immunoblotting, ELISA, and RIA methods. Use of Chinese Spring nullisomic-tetrasomic lines showed that several narrow specificity antibodies bound specifically to gliadins encoded by genes located on a single chromosome. In at least one case, antibodies bound to genetic "blocks" of gliadins, indicating that these block members have structural homology. However, often not all gliadins of a block were recognized by an antibody. For broad-specificity antibodies and some narrow-specificity antibodies, structural genes on several chromosomes were important. Studies with several primitive wheat species indicated that, while antibodies usually bound gliadins from the same genome in bread and primitive wheats, antibodies sometimes bound proteins of quite differing mobilities in the two wheat types. Use of antibodies to identify gliadin blocks is simpler than block analysis based on performing crosses, and should be of value in monitoring genotype/end-use quality relationships. PMID- 24212860 TI - A note on the application of diallel crosses for the analysis of genetic variation in natural populations. AB - The complete diallel cross among homozygous lines can be a useful tool to analyze the genetic architecture of natural populations. However, it represents the natural population only approximately, in particular if the number of lines is small and the analyzed traits exhibit inbreeding depression or other forms of directional dominance. Some incorrect expected mean squares that can be found in the literature suggest tests for genetic variance components that can be misleading under such circumstances. Expected mean squares for a factorial analysis and for a modified Hayman analysis are presented and the effect of the number of lines and directional dominance is discussed. PMID- 24212861 TI - Distribution and organization of a tandemly repeated 352-bp sequence in the oryzae family. AB - A 352-bp EcoRI fragment from rice DNA was cloned and shown to be a member of a tandem repeat. Sequence determination revealed homologies with human alpha satellite DNA and maize knob heterochromatin specific repeat. This 352-bp sequence is highly specific for the AA genome of rice. However, copy number and sequence organization are variable, depending on the accession analyzed. Several examples of amplification were observed in O. rufipogon and O. longistaminata. Use of resolutive polyacrylamide gel electrophoresis and 4-bp cutter enzymes allowed one to distinguish between the Indica and Japonica subtypes of O. sativa. The same method also discriminates between two groups of O. rufipogon, the presumed ancestor of O. sativa, suggesting that the present day Indica and Japonica subtypes originated independently from two O. rufipogon distinct populations. PMID- 24212862 TI - Crossbreeding effects after long-term selection for purebred performance: a model experiment with mice : 2. Performance of three-breed crosses. AB - Results are presented from two replicated three-breed cross diallels that were conducted after 20 generations of selection for purebred performance in mice. The selection criteria for the different lines were: litter size at birth (LS), weaning weight at 4 weeks (WW), weight gain from week 4 to week 6 (WG), and body fat content at week 6 (FT). Additionally, a random-mating control line (C) was kept. Significant maternal heterosis was found in litter size and weaning weight. Estimates of maternal heterosis in litter size were very high, ranging from 17 to 50% of the mean of the corresponding single crosses. Maternal heterosis in weaning weight usually was negative and ranged from +9 to -11%. Significant maternal heterosis in feed efficiency and weaning weight could only be found in a few cases. Total performance of three-breed crosses was highly superior to that of single crosses and purebreds. Means of the corresponding purebreds or single crosses were of little use in predicting three-breed cross performance. PMID- 24212863 TI - Plant regeneration from embryogenic cell suspensions derived from anther cultures of barley (Hordeum vulgare L.). AB - We have established embryogenic cell suspension cultures of barley (Hordeum vulgare L. cultivars Igri, Gimpel, Princesse, and Baronesse) from anther-derived embryogenic callus. Suspension cultures of cultivars Igri and Gimpel were regenerable. The most successful cultivar was Igri, from which a number of independent cell lines producing plantlets were established. Plants could be transferred to soil; up to now, 50% of more than 200 regenerated plants were morphologically normal and fertile. The relative frequency of sterile plants increased as suspensions aged. Suspensions older than 1 year produced embryogenic callus but only albino plantlets could be regenerated. PMID- 24212864 TI - Molecular systematics of Brassica and allied genera (Subtribe Brassicinae, Brassiceae) -chloroplast genome and cytodeme congruence. AB - Chloroplast DNA restriction sites for 20 endonucleases were mapped using cpDNA probes from Brassica juncea and site variation was surveyed in 33 diploid taxa of the Subtribe Brassicinae. A total of 419 mutations was observed, including both site (i.e., gain/ loss) and fragment length (i.e., insertions or deletions); 221 (53%) mutations showed variation at the interspecific level. Phylogenetic analysis indicated a clear division of the subtribe into two ancient evolutionary lineages. These were (I) the "Nigra" lineage: Brassica nigra, B. fruticulosa, B. tournefortii, Sinapis pubescens, S. alba, S. flexuosa, S. arvensis, Coincya cheiranthos, Erucastrum canariense, and Hirschfeldia incana, and (II) the "Rapa/ Oleracea" lineage: Brassica rapa, B. oleracea ssp. oleracea and ssp. alboglabra, B. rupestris-villosa complex (B. rupestris, B. drepanensis, B. macrocarpa, B. villosa), B. barrelieri, B. deflexa, B. oxyrrhina, B. gravinae, Diplotaxis erucoides, D. tenuifolia, Eruca sativa, Raphanus raphanistrum, R. sativus, and Sinapis aucheri. In the "Nigra" lineage, Brassica nigra was most closely related to the annual Sinapis species, S. arvensis and S. alba. In the "Rapa/Oleracea" lineage, the Brassica rapa and B. oleracea genomes formed a distinct group whose closest relatives were the wild species of the B. oleracea (n=9) complex (i.e., B. rupestris-villosa complex). Species with n=7 chromosomes exist in both lineages. Hirschfeldia incana (n=7), in the "Nigra" lineage, was most closely related to Sinapis pubescens. In the "Rapa/Oleracea" lineage three taxa with n=7 B. deflexa, D. erucoides, and S. aucheri - were closely related, advanced in the lineage, and were the closest apparent relatives (particularly D. erucoides) to B. rapa, B. oleracea, and its wild relatives. Levels of genetic divergence suggested by the cpDNA data were consistent with cytodeme recognition in the subtribe, but provided evidence for inconsistencies in the current generic delimitations based on morphology. Very low levels of genetic divergence were evident among taxa/accessions within a cytodeme. Raphanus was closely related to the Brassica rapa and B. oleracea genomes and clearly belongs in Subtribe Brassicinae. Several cytoplasmic genetic markers of potential use in plant breeding programs were identified for each of the cytodemes. PMID- 24212865 TI - A homologous expression system for cloned zein genes. AB - Expression of the genes encoding the 10-, 15-, and 27-kDa zeins is maintained in suspension cultures derived from developing endosperm tissue of maize (Zea mays L.). Although expression of these genes is reduced in endosperm cultures as compared with that in endosperm tissue from developing kernels, it remains specific to the origin of explant, since no transcripts are detected in leaf tissue-derived suspension cultures. Transcript sizes are identical to those in developing seed endosperm tissue. Furthermore, accurate transcription initiation of the 10- and 27-kDa zein genes is observed by S1 nuclease mapping. Protoplasts isolated from endosperm cultures are capable of expressing foreign genes when transfected by electroporation. We demonstrate that the 5' flanking sequences of the 10- and 27-kDa zein genes are capable of promoting chloramphenicol acetyltransferase (CAT) gene expression in these transfected protoplasts. Our observations show that these maize endosperm cultures can be used as an efficient homologous system to study transcriptional regulation of zein genes. PMID- 24212866 TI - Preparation and flow cytometric analysis of metaphase chromosomes of tomato. AB - A procedure for the preparation of tomato chromosome suspensions suitable for flow cytometric analysis is described. Rapidly growing cell suspension cultures of Lycopersicon esculentum cv VFNT cherry and L. pennellii LA716 were treated with colchicine to enrich for metaphase chromosomes. Metaphase indices between 20 and 35% were routinely obtained when cultures were exposed to 0.1% colchicine for 15-18 h after 2 days of subculture. Mitotic cells were isolated by brief treatment with cell wall digesting enzymes in a medium with low osmolarity (~325 mOsm/kg of H52O). The low osmolarity medium was needed to avoid the chromosome clumping and decondensation seen in standard media. Suspensions of intact chromosomes were prepared by lysing swollen protoplasts in various buffers (MgSO4, polyamines, hexylene glycol, or KCl-propidium iodide) similar in contents to the buffers used to isolate mammalian chromosomes. For univariate flow cytometric analysis, chromosome suspensions were stained with a fluorescent DNA binding stain (propidium iodide, Hoechst 33258, mithramycin, or chromomycin A3) and analyzed using an EPICS flow cytometer (Profile Analyzer or 753). Peaks for the chromosomes, chromatids, clumps of chromosomes, nuclei, and fluorescent debris were seen on a histogram of log of fluorescence intensity, and were confirmed by microscopic examination of the objects collected by flow-sorting. Chromosome suspensions prepared in MgSO4 buffer have the highest frequency of intact chromosomes and the least fluorescent cellular debris. Peaks similar to theoretical univariate flow karyotypes of tomato chromosomes were seen on the observed univariate flow karyotypes, but were not as well resolved. Bivariate flow analysis of tomato chromosome suspension using double-stain combination, Hoechst 33258 and chromomycin A3, and two laser beams showed better resolution of some chromosomes. PMID- 24212867 TI - A map of rye chromosome 2R using isozyme and morphological markers. AB - The segregation of isozymic loci for leaf peroxidases (L2Per) has been investigated in backcrosses and F2 offspring of rye lines having purple seeds (Ps) and monstrosum ears (mo). The Ps, L2Per-3b, mo, and L2Per-2 loci were linked. The Ps and mo loci have been previously located on the 2R chromosome, and the L2Per-3b and L2Per-2 loci have been located on the 2RS chromosome arm. The results favor the gene order Ps ... L2Per-3b ... mo ... L2Per-2 or Ps ... mo... L2Per-3b ... L2Per-2. The position of the loci relative to the centromere is still not known, but the obtained results suggest that the mo locus could be located on the 2RS chromosome arm. On the basis of previously reported linkage groups, the most probable arrangement of the loci located on chromosome 2R is: dw2 ... Ps ... (L2Per-3a ... L2Per-3b ... mo) ... L2Per-2. It has not been possible to know the position of L2Per-4 loci (also located on 2RS chromosome arm) relative to L2Per-3a and L2Per-3b loci. PMID- 24212868 TI - Effect of nurse cultures on the production of macro-calli and fertile plants from maize embryogenic suspension culture protoplasts. AB - Fertile plants have been obtained from maize (Zea mays L.) embryogenic suspension culture protoplasts. Friable, embryogenic callus initiated from an immature embryo from a cross involving the genotypes A188, B73, and Black Mexican sweetcorn was used to establish a rapidly growing embryogenic suspension culture. After nine months in culture, high yields of viable protoplasts (30*10(6)/ gram fresh weight) were obtained following a 1.5 hour enzymatic digestion. Protoplasts cultured with feeder cells divided and formed embryogenic callus, from which male and female fertile plants were regenerated. Protoplast-derived R1 plants were self-pollinated and immature R2 embryos isolated for callus initiation. Female fertile plants have also been produced from protoplasts isolated from an R2 derived suspension culture. Significant interactions between protoplast and feeder-cell lines were observed. PMID- 24212869 TI - Isolation of protoplasts from developing barley endosperm: a tool for transient expression studies. AB - We have developed a method for the routine isolation of protoplasts from developing starchy endosperm of barley (Hordeum vulgare L.). Preplasmolysis of the intact endosperms, a low concentration of hydrolytic enzymes and gravity sedimentation before any centrifugation step, were crucial factors for a good preparation. Best yields were obtained early after pollination (8-13 days) or with mutants with low starch content. Transient expression of a reporter gene under the control of the 35S promoter, after polyethyleneglycol transfection of endosperm protoplasts, was of the same order as that found in coleoptile derived protoplasts. No significant difference in expression was found for a given tissue between cv. Bomi and its mutant Riso 1508. PMID- 24212870 TI - Induction of division and differentiation of somatic embryos in the leaf epidermis of Gaillardia picta. AB - Somatic embroys and subsequent plant regeneration were obtained from isolated leaf epidermis of Gaillardia picta. Abaxial and adaxial epidermal peels (monolayer) from 45 days old aseptic seedlings were isolated and segments measuring 5 mm x 3 mm were cultured on B5 basal medium supplemented with various growth regulators such as naphthaleneacetic acid or indolebutyric acid and benzylaminopurine or kinetin. Within 12 h of culture the epidermal cells showed receding of cytoplasm from the walls. After 48 h of incubation 3 or 4 localized zones, each consisting of 3-8 cells that accumulated cytoplasm and stained densely, were observed. Mitotic divisions occurred in these zones on day 3 of culture and localized masses of callus were observed in 95% of the cultures after 10 days. In another 5 days, the callus differentiated somatic embryos or roots, depending on the growth regulators and their concentration in the medium. PMID- 24212871 TI - The role of ethylene and reducing agents on anther culture response of tetraploid potato (Solanum tuberosum L.). AB - The role of ethylene in embryogenesis of cultured potato anthers was studied indirectly by testing various substances known to affect ethylene formation. The reducing agents ascorbic acid and L-cysteine prevented browning of anther cultures and significantly stimulated embryogenesis. Embryogenesis was also promoted by the use of the ethylene inhibitors AgNO3 and n-propyl-gallate and by the polyamines spermidine and putrescine. The use of the ethylene releasing compound ethrel significantly inhibited embryogenesis. PMID- 24212872 TI - A novel type of somatic embryogenesis in Coffea arabica. AB - A novel type of somatic embryogenesis characterized by an efficient and highly synchronized embryo formation was observed in embryogenic callus of Coffea arabica initiated on Murashige and Skoog medium containing kinetin (4 mg/l) and 2,4-D (1 mg/l). It occurs in suspension and goes along with the suppression of "High Frequency Somatic Embryo Induction" (HFSE). This is achieved by favoring during cultivation senescence-or necrosis-like processes which apparently do not impair the competence for embryogenesis. Since the resulting embryos germinate at a rate of 94.5 % without the need of a maturation step, we propose the term "Self Controlled Somatic Embryogenesis" (SCSE).In addition, HFSE was optimized using half-strength liquid medium with 0.1 mg/l kinetin and 0.25 mg/l 2,4-D for proliferation of embryonic tissue, and 2.6 mg/l ABA for maturation of embryos. Yields as well as germination rates of HFSE embryos were markedly lower as compared to SCSE. PMID- 24212873 TI - Direct cell to cell transfer of organelles by microinjection. AB - A new technique for transfer of organelles to plant cells is presented. The organelles are removed from the donor protoplast by micromanipulation and microinjected directly into the acceptor cells. First results obtained by this technique for transfer of chloroplasts and fluorescently labelled mitochondria are presented. PMID- 24212874 TI - Enhancement of shoot regeneration potential by liquid medium culture from mature cotyledons of sunflower (Helianthus annuus L.). AB - We describe here a liquid culture system for the regeneration of shoots at high frequencies from mature cotyledon tissues of three genotypes of sunflower (Helianthus annuus L.) one of which had previously been found to be recalcitrant to regeneration when cotyledons were cultured on solid medium. Cotyledons were excised from 2-day-old seedlings and incubated in liquid Murashige and Skoog's modified medium supplemented with 5.4 MUM naphthaleneacetic acid (NAA) and 4.4 MUM benzylaminopurine (BAP). After two weeks in culture, the whole upper surface of regenerating explants was covered with green shootlets. The percentages of regenerating explants of three genotypes varied between 60 and 70%, and the number of shoots per regenerating explant was highly increased. The shootlets were transferred to solid Murashige and Skoog's medium allowing shoot development, then to rooting medium. Rooted plantlets were successfully acclimatized and gave fertile plants. The role of liquid medium culture in the induction of sunflower regeneration is discussed. PMID- 24212875 TI - High frequency somatic embryogenesis and plant regeneration in tissue cultures of Codonopsis lanceolata. AB - Culture conditions for high frequency somatic embryogenesis and plant regeneration from cotyledonary explants of Codonopsis lanceolata are described. The maximum induction frequency of somatic embryos from cotyledonary explants was 80% on Murashige and Skoog (MS) medium containing 6% sucrose with 1 mg/l 2,4 dichlorophenoxyacetic acid and 10% coconut water. Upon transfer onto MS basal medium containing 3% sucrose, most somatic embryos developed into plantlets. PMID- 24212876 TI - Protoplast fusion-derived Ogura male sterile cauliflower with cold tolerance. AB - Cauliflower (Brassica oleracea L. ssp. botrytis) protoplasts with Ogura male sterile and fertile B. oleracea cytoplasms were fused, producing plants with an array of organellar types. Plants with Ogura mitochondria were male sterile; those with B. oleracea chloroplasts were cold tolerant. In some fusions, unfused parental protoplasts were eliminated by double inactivation with iodoacetate and gamma-irradiation; in others, fused protoplasts were physically isolated by micromanipulation or by cell sorting. Double inactivation fusions produced the most plants, including many which were male sterile, female fertile, cold tolerant and diploid. PMID- 24212877 TI - Molecular analysis of the nuclear organellar genotype of somatic hybrid plants between tomato (Lycopersicon esculentum) and Lycopersicon chilense. AB - Somatic hybrid plants were recovered following fusion of leaf mesophyll protoplasts isolated from tomato (Lycopersicon esculentum) cultivar UC82 with protoplasts isolated from suspension cultured cells of L. chilense, LA 1959. Iodoacetate was used to select against the growth of unfused tomato protoplasts. Two somatic hybrids were recovered in a population of 16 regenerants. No tomato regenerants were recovered; all of the non-hybrid regenerants were L. chilense. The L. chilense protoplast regenerants were tetraploid. The hybrid nature of the plants was verified using species-specific restriction fragment length polymorphisms for the nuclear, chloroplast and mitochondrial genomes. The somatic hybrids had inherited the chloroplast DNA of the tomato parent, and portions of the mitochondrial DNA of the L. chilense parent. The somatic hybrids formed flowers and developed seedless fruit. PMID- 24212878 TI - Somatic embryogenesis in protoplast derived calli of cultivated jute, Corchorus capsularis L. AB - Protoplasts were isolated from cotyledon, hypocotyl and mesophyll cells of Corchorus capsularis L., a major fibre crop, by one step enzyme digestion method. They were further cultured successfully on modified KM-8p (Kao and Michayluk, 1975) medium to form microcalli. The required cultural conditions could be used to achieve 34% to 78% plating efficiency, depending upon the source of protoplasts. Hypocotyl protoplasts gave the highest plating efficiency. On transfer to regeneration medium, somatic embryos developed at high frequency. The present success is a significant step forward in the development of meaningful plant cell culture methods for application in jute. PMID- 24212879 TI - Adipsia increases risk of death in patients with central diabetes insipidus. AB - Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death. PMID- 24212880 TI - Prognosis and growth activity depend on patient age in clinical and subclinical papillary thyroid carcinoma. AB - In this review, we focused on the patient age as an indicator of tumor growth and prognostic significance in both clinical papillary thyroid carcinoma (PTC) and subclinical papillary microcarcinoma (PMC: PTC <= 1 cm). In clinical PTC, young age (< 30 years) and old age (>= 60 years) significantly affected the disease free survival of patients, and old age was a strong predictor of carcinoma death. In contrast, in subclinical PMC, growth activity significantly decreased with patient age, and young age (< 40 years) was an independent predictor of carcinoma growth, indicating that old patients with subclinical PMC are the best candidates for observation without immediate surgery. Taken together, our findings indicate that the role of patients' age as an indicator of tumor growth differs significantly between clinical PTC and subclinical PMC. PMID- 24212881 TI - Lower beta cell function relates to sustained higher glycated albumin to glycated hemoglobin ratio in Japanese patients with type 2 diabetes. AB - The aim of this study was to clarify the relationship between baseline beta cell function and future glycated albumin (GA) to glycated hemoglobin ratio (GA/HbA1c) in patients with type 2 diabetes. In our retrospective cohort, 210 type 2 diabetic patients who had been admitted to our hospital and in whom HbA1c and GA had been measured at baseline and 2 years after admission were included in this study. Baseline beta cell function was assessed by postprandial C-peptide immunoreactivity index (PCPRI) during admission. With intensification of treatment during admission, HbA1c and GA were significantly decreased 1 year and 2 years after admission. While baseline HbA1c was not significantly correlated with HbA1c after 2 years, baseline GA/HbA1c was strongly correlated with GA/HbA1c after 2 years (r = 0.575, P <0.001). When the patients were divided into two groups according to median PCPRI, patients with low PCPRI showed higher GA/HbA1c both at baseline and after 2 years compared to those with high PCPRI. There was a significant negative correlation between PCPRI and GA/HbA1c after 2 years (r = 0.379, P <0.001). Multiple regression analysis revealed that PCPRI was an independent predictor of GA/HbA1c after 2 years. In conclusion, our findings suggest that lower beta cell function is associated with sustained higher GA/HbA1c ratio in patients with type 2 diabetes. PMID- 24212882 TI - Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. AB - The contribution of cis-regulatory mutations to human disease remains poorly understood. Whole-genome sequencing can identify all noncoding variants, yet the discrimination of causal regulatory mutations represents a formidable challenge. We used epigenomic annotation in human embryonic stem cell (hESC)-derived pancreatic progenitor cells to guide the interpretation of whole-genome sequences from individuals with isolated pancreatic agenesis. This analysis uncovered six different recessive mutations in a previously uncharacterized ~400-bp sequence located 25 kb downstream of PTF1A (encoding pancreas-specific transcription factor 1a) in ten families with pancreatic agenesis. We show that this region acts as a developmental enhancer of PTF1A and that the mutations abolish enhancer activity. These mutations are the most common cause of isolated pancreatic agenesis. Integrating genome sequencing and epigenomic annotation in a disease relevant cell type can thus uncover new noncoding elements underlying human development and disease. PMID- 24212884 TI - Genome-wide association study using cellular traits identifies a new regulator of root development in Arabidopsis. AB - With the increased availability of high-resolution sequence information, genome wide association (GWA) studies have become feasible in a number of species. The vast majority of these studies are conducted in human populations, where it is difficult to provide strong evidence for the functional involvement of unknown genes that are identified using GWA. Here we used the model organism Arabidopsis thaliana to combine high-throughput confocal microscopy imaging of traits at the cellular level, GWA and expression analyses to identify genomic regions that are associated with developmental cell-type traits. We identify and characterize a new F-box gene, KUK, that regulates meristem and cell length. We further show that polymorphisms in the coding sequence are the major causes of KUK allele dependent natural variation in root development. This work demonstrates the feasibility of GWA using cellular traits to identify causal genes for basic biological processes such as development. PMID- 24212885 TI - The complete genomes of subgenotype IA hepatitis A virus strains from four different islands in Indonesia form a phylogenetic cluster. AB - Despite the high endemicity of hepatitis A virus (HAV) in Indonesia, genetic information on those HAV strains is limited. Serum samples obtained from 76 individuals during outbreaks of hepatitis A in Jember (East Java) in 2006 and Tangerang (West Java) in 2007 and those from 82 patients with acute hepatitis in Solo (Central Java), Denpasar on Bali Island, Mataram on Lombok Island, and Makassar on Sulawesi Island in 2003 or 2007 were tested for the presence of HAV RNA by reverse transcription PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 34 serum samples had detectable HAV RNA, including at least one viremic sample from each of the six regions. These 34 strains were 96.3-100 % identical to each other and formed a phylogenetic cluster within genotype IA. Six representative HAV isolates from each region shared 98.3-98.9 % identity over the entire genome and constituted a IA sublineage with a bootstrap value of 100 %, consisting of only Indonesian strains. HAV strains recovered from Japanese patients who were presumed to have contracted HAV infection while visiting Indonesia were closest to the Indonesian IA HAV strains obtained in the present study, with a high identity of 99.5-99.7 %, supporting the Indonesian origin of the imported strains. These results indicate that genetic analysis of HAV strains indigenous to HAV-endemic countries, including Indonesia, are useful for tracing infectious sources in imported cases of acute hepatitis A and for defining the epidemiological features of HAV infection in that country. PMID- 24212886 TI - Prevalence study and phylogenetic analysis of group C porcine rotavirus in the Czech Republic revealed a high level of VP6 gene heterogeneity within porcine cluster I1. AB - Group C rotavirus (RVC) has been described to be a causative agent of gastroenteritis in humans and animals. In the current study, the presence of porcine RVC was confirmed in 25.6 % of 293 porcine faecal samples collected from seven Czech farms. A significantly larger (p < 0.05) number of RVC-positive samples was detected in groups of finisher pigs and post-weaning piglets (4-12 weeks of age). Phylogenetic analysis of nine RVC-positive Czech strains and their comparison with available sequence data for the gene encoding RVC group antigen VP6 revealed two separate lineages within porcine cluster I1. PMID- 24212887 TI - Identification of equine influenza virus infection in Asian wild horses (Equus przewalskii). AB - An outbreak of equine influenza was observed in the Asian wild horse population in Xinjiang Province, China, in 2007. Nasal swabs were collected from wild horses and inoculated into 9-10-day SPF embryonated eggs. The complete genome of the isolate was sequenced. A comparison of the amino acid sequence revealed that the isolate was an equine influenza virus strain, which we named A/equine/Xinjiang/4/2007. Each gene of the virus was found to have greater than 99 % homology to equine influenza virus strains of the Florida-2 sublineage, which were circulating simultaneously in China, and a lesser amount of homology was found to the strain A/equine/Qinghai/1/1994 (European lineage), which was isolated during the last outbreak in China. These observations were confirmed by phylogenetic analysis. In addition, the deduced amino acid sequence of the neuraminidase of the A/equine/Xinjiang/4/2007 strain was identical to that of A/equine/California/8560/2002, an American isolate, and was found to be similar to those of Florida-2 strains found in other countries by comparing them with nine other field strains that were isolated in China from 2007 to 2008. It is suggested that the neuraminidase segment of A/equine/Xinjiang/4/2007 may have been obtained from equine influenza virus strains from other countries. We report for the first time an outbreak of equine influenza in the Asian wild horse population, and the complete genome of the virus is provided and analyzed. PMID- 24212888 TI - A distinct strain of chickpea chlorotic dwarf virus (genus Mastrevirus, family Geminiviridae) identified in cotton plants affected by leaf curl disease. AB - As part of a study to determine the diversity of whitefly-transmitted viruses (genus Begomovirus, family Geminiviridae) associated with cotton leaf curl disease in Pakistan, leaf samples from cotton plants showing typical leaf curl disease symptoms were collected in various locations of Punjab province. Sequence analysis of full-length virus clones (~2.7 kb) showed plants to be infected with the begomovirus cotton leaf curl Burewala virus, the only virus identified in cotton in the Punjab since 2001. Surprisingly, a second virus, the leafhopper transmitted chickpea chlorotic dwarf virus (CpCDV) of the genus Mastrevirus (family Geminiviridae), was identified in a small number of plants. The sequences of four CpCDV isolates from cotton originating from geographically distinct areas in Punjab were obtained. Analysis of the sequences showed them to represent a distinct, newly identified strain of CpCDV with the highest levels of nucleotide sequence identity to isolates of CpCDV strains C and D that have been identified previously in Pakistan. CpCDV has not been identified previously in cotton. The significance of this finding is discussed. PMID- 24212883 TI - A large-scale screen for coding variants predisposing to psoriasis. AB - To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis. PMID- 24212889 TI - The family Parvoviridae. AB - A set of proposals to rationalize and extend the taxonomy of the family Parvoviridae is currently under review by the International Committee on Taxonomy of Viruses (ICTV). Viruses in this family infect a wide range of hosts, as reflected by the longstanding division into two subfamilies: the Parvovirinae, which contains viruses that infect vertebrate hosts, and the Densovirinae, encompassing viruses that infect arthropod hosts. Using a modified definition for classification into the family that no longer demands isolation as long as the biological context is strong, but does require a near-complete DNA sequence, 134 new viruses and virus variants were identified. The proposals introduce new species and genera into both subfamilies, resolve one misclassified species, and improve taxonomic clarity by employing a series of systematic changes. These include identifying a precise level of sequence similarity required for viruses to belong to the same genus and decreasing the level of sequence similarity required for viruses to belong to the same species. These steps will facilitate recognition of the major phylogenetic branches within genera and eliminate the confusion caused by the near-identity of species and viruses. Changes to taxon nomenclature will establish numbered, non-Latinized binomial names for species, indicating genus affiliation and host range rather than recapitulating virus names. Also, affixes will be included in the names of genera to clarify subfamily affiliation and reduce the ambiguity that results from the vernacular use of "parvovirus" and "densovirus" to denote multiple taxon levels. PMID- 24212890 TI - Bronchiolitis obliterans syndrome leads to a functional deterioration of the acinus post lung transplant. AB - Bronchiolitis obliterans syndrome (BOS) limits long-term survival of lung transplant recipients, and airflow obstruction in these patients likely originates in the small airways. 61 double lung transplant recipients performed multiple breath nitrogen washouts to obtain indices of acinar and conductive ventilation heterogeneity (Sacin, Scond). There was a significant association of BOS status with Sacin (Kruskal-Wallis; p<0.001) but not with Scond (p=0.1). These results demonstrate that it is the structural alteration of the terminal bronchioles, generating ventilation heterogeneity at the level of the diffusion front, and not the bronchioles located more proximally, that is driving the airflow obstruction that determines BOS status. PMID- 24212891 TI - Letter in response to Tashkin et al: Limited generalisability of uplift findings to clinical practice. PMID- 24212892 TI - The active identification and management of chronic refractory breathlessness is a human right. AB - Chronic refractory breathlessness is defined as breathlessness at rest or on minimal exertion that will persist chronically despite optimal treatment of the underlying cause(s). At any time, 1% of the population report a modified Medical Research Council dyspnoea score of >= 3 chronically. Despite the prevalence, severity and chronicity of this symptom and an evidence base of affordable and safe interventions, chronic refractory breathlessness remains grossly undertreated. Many patients and clinicians accept the presence of the chronic refractory breathlessness as an inevitable part of an illness, with no thought of treating the symptom despite an evidence base for its safe treatment. Consensus statements from major respiratory clinician organisations now endorse such a clinical course. Failure to inquire about, assess and properly treat chronic refractory breathlessness with opioids as outlined in specialist clinical guidelines is now an unacceptable level of care ethically and is, arguably, a breach of people's human rights. Adequate pain control through access to pain relief is now accepted as a human right and, given its burden across the world, the symptomatic treatment of chronic refractory breathlessness should be seen in exactly the same way. PMID- 24212893 TI - Seasonally fluctuating bark proteins are a potential form of nitrogen storage in three temperate hardwoods. AB - The inner bark tissues of three temperate hardwoods contain specific proteins which undergo seasonal fluctuations. Increases in particular proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, occur within the bark of several Acer, Populus and Salix spp. during late summer and early autumn. These proteins are abundant in the bark throughout the winter and their levels decline the following spring. Light and electron microscopy showed that the parenchyma cells of the inner bark are packed with spherical organelles throughout the overwintering period. These organelles are rich in protein and analogous to protein bodies found in cells of mature seeds. The protein bodies of the parenchyma cells are replaced by large central vacuoles during spring and summer, presumably as a result of the mobilization of the storage protein and fusion of the protein bodies. The high levels of specific proteins in inner bark tissues and the presence of protein bodies within the parenchyma cells indicate that the living cells of the bark act as a nitrogen reserve in overwintering temperate hardwoods. PMID- 24212894 TI - Photoaffinity labeling and partial purification of the putative plant receptor for the fungal wilt-inducing toxin, fusicoccin. AB - The high-affinity fusicoccin-binding protein (FCBP) was solubilized from plasma membrane vesicles prepared from leaves of Vicia faba L. by aqueous two-phase partitioning. Conditions for the solubilization of intact FCBP-radioligand complexes were worked out. About 60-70% of the complexes can be solubilized with 50-60 mM nonanoyl-N-methylglucamide in the presence of 1 mg. ml(-1) soybean phosphatidylcholine, type IV S, and 20% (v/v) glycerol at pH 5.5. The slow dissociation of the radioligand, 9'-nor-fusicoccin-8'-alcohol-[(3)H] from the FCBP at low temperatures permits the purification of FCBP-radioligand complexes at 4-10 degrees C by fast protein liquid chromatography on anion-exchange and gel permeation columns. The FCBP, extracted from plasma membranes with cholate and chromatographed in the presence of this detergent, gave an apparent molecular mass (Mr) of 80+/-20 kDa on gel permeation columns under the conditions used. By comparison of the elution profiles of the fraction most enriched in FCBP radioligand complexes with polypeptide patterns obtained on sodium dodecyl sulfate-polyacrylamide gels, a polypeptide with an Mr of approx. 34kDa co separated with the radioactivity profile. A second, faint band of approx. 31 kDa was sometimes also observed co-electrophoresing. Photoaffinity labeling of plasma membrane vesicles with the new compound 9'-nor-8'[(3,5-[(3)H]-4 azidobenzoy)ethylenediamine]-fusicoccin ([(3)H]ABE-FC) and subsequent separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis labeled a single band with an Mr of 35+/-1 kDa. Labeling in this band was strongly reduced when the membranes were incubated with [(3)H]ABE-FC in the presence of 0.1-1 MUM fusicoccin. From our data, we conclude (i) that the 34-35-kDa polypeptide represents the FCBP and (ii) that in detergent extracts of plasma membranes this polypeptide is probably present as a di- or trimeric structure. PMID- 24212895 TI - Development of the preprophase band from random cytoplasmic microtubules in guard mother cells of Allium cepa L. AB - The organization of microtubule (MT) arrays in the guard mother cells (GMCs) of A. cepa was examined, focussing on the stage at which a longitudinal preprophase band (PPB) is established perpendicular to all other division planes in the epidermis. In the majority of young GMCs, including those seen just after asymmetric division, MTs are distributed randomly throughout the cortex and inner regions of the cytoplasm. Few MTs are associated with the nuclear surface. As the GMCs continue to develop, MTs cluster around the nucleus and a PPB appears as a wide longitudinal band. Microtubules also become prominent between the nucleus and the periclinal and transverse walls, while they decrease in number along the radial longitudinal walls. The PPB progressively narrows by early prophase, and a transversely oriented spindle gradually ensheaths the nucleus. These observations indicate that the initial, broad PPB is organized by a rearrangement of the random cytoplasmic array of MTs. Additional reorganization is responsible for MTs linking the nucleus and the cortex in the future plane of the cell plate, and for narrowing of the PPB. PMID- 24212896 TI - Localization of ribulose-bisphosphate carboxylase-oxygenase and its putative binding protein in the cell envelope of Chromatium vinosum. AB - Antibodies to the large and small subunits of ribulose-bisphosphate carboxylase oxygenase (RuBisCO; EC 4.1-1.39) and a putative binding protein (PBP) for RuBisCO from Chromatium vinosum have been used to localize these proteins in thin sections. Immunogold techniques employing single and double antibodies establish that RuBisCO and the RuBisCO PBP are concentrated in the cell envelope of C. vinosum. PMID- 24212897 TI - Ultrastructural changes associated with the accumulation and secretion of sanguinarine in Papaver bracteatum suspension cultures treated with fungal elicitor. AB - Suspension cultures of Papaver bracteatum Arya II Lindl., grown without hormone in the presence of conidial extracts of Verticillium dahliae Kleb., accumulate millimolar quantities of the benzophenanthridine alkaloid, sanguinarine. Under the fluorescence microscope, the elicitor-treated cells display an orange-yellow fluorescence characteristic of sanguinarine, primarily near the periphery of the cells. Electron-microscopic inspection showed the presence of slightly dilated endoplasmic reticulum and of electron-dense protuberances on the tonoplast of large central vacuoles. These osmiophilic aggregates lining the tonoplast bud into spherical bodies, appear to become detached from the membrane and are released into the vacuole. Upon subcellular fractionation of elicited cells on Renografin step gradients, sanguinarine was found to be distributed in all bands but with 86% concentrated in the gradient pellet. Analysis of the pellet by electron microscopy showed that it contained electron-dense fragments similar to the osmiophilic bodies observed on the tonoplast of intact elicited cells. In elicited cell cultures, most of the sanguinarine was recovered from medium in a 100.g sedimenting, cell-free, particulate fraction accounting for as much as 85% of the media sanguinarine and 62% of the total sanguinarine. The sanguinarine rich 100.g media pellet was determined to be two-thirds protein, one-third RNA and was essentially devoid of phenolics, phospholipid and DNA. The pellet consisted of electrondense material and cytoplasmic remnants resembling those found in the Renografin pellet and tonoplast aggregates of intact cells. When placed under hypotonic conditions or extracted with aqueous buffer, pH 3-11, the pellet did not release sanguinarine. These observations provide evidence for storage of sanguinarine at electron-dense deposits which occur on the tonoplast and as freely floating bodies in vacuoles. PMID- 24212898 TI - Immunolocalization of avenin and globulin storage proteins in developing endosperm of Avena sativa L. AB - The seed storage proteins of oats (Avena sativa L.) are synthesized and assembled into vacuolar protein bodies in developing endosperm tissue. We used double-label immunolocalization to study the distribution of these proteins within protein bodies of the starchy endosperm. When sections of developing oat endosperm sampled 8 d after anthesis were stained with uranyl acetate and lead citrate, the vacuolar protein bodies consisted of light-staining regions which were usually surrounded by a darker-staining matrix. Immunogold staining of this tissue demonstrated a distinct segregation of proteins within protein bodies; globulins were localized in the dark-staining regions and prolamines were localized in the light-staining regions. We observed two additional components of vacuolar protein bodies: a membranous component which was often appressed to the outside of the globulin, and a granular, dark-staining region which resembled tightly clustered ribosomes. Neither antibody immunostained the membranous component, but the granular region was lightly labelled with the anti-globulin antibody. Anti globulin immunostaining was also observed adjacent to cell walls and appeared to be associated with plasmodesmata. Immunostaining for both antigens was also observed within the rough endoplasmic reticulum. Based on the immunostaining patterns, the prolamine proteins appeared to aggregate within the rough endoplasmic reticulum while most of the globulin appeared to aggregate in the vacuole. PMID- 24212899 TI - Plant regeneration from indica rice (Oryza sativa L.) protoplasts. AB - Rice (Oryza sativa L.) plants of the indica cultivar IR54 were regenerated from protoplasts. Conditions were developed for isolating and purifying protoplasts from suspension cultures with protoplast yields ranging from 1.10(6) to 15.10(6) viable protoplasts/1 g fresh weight. Protoplast viability after purification was generally over 90%. Protoplasts were cultured in a slightly modified Kao medium in a Petri plate by placing them onto a Millipore filter positioned on top of a feeder (nurse) culture containing cells from a suspension culture of the japonica rice, Calrose 76. Plating efficiencies of protoplasts ranged from 0.5 to 3.0%; it was zero in the absence of the nurse culture. Protoplast preparations usually contained no contaminating cells, and when present, the number of cells never exceeded 0.1% of the protoplasts. After three weeks the Millipore filter with callus colonies were transferred off feeder cells and onto a Linsmaier and Skoog type medium for an additional three weeks. Selected callus colonies that had embryo-like structures were then transferred to regeneration medium containing cytokinins, and regeneration frequencies up to 80% were obtained. Small shoots emerged and were transferred to jars for root development prior to transferring to pots of soil and growing the plants to maturity in growth chambers. Of the cytokinins evaluated, N(6)-benzylaminopurine was the most effective in promoting shoot formation; however, kinetin was also somewhat effective. Regeneration medium could be either an N6 or Murashige and Skoog basal medium. Of 76 plants grown to maturity, 62 were fertile, and the plant heights averaged about three fourths the height of seed-grown plants.Two other suspension cultures of IR54, one developed from the protoplast callus of the initial IR54 line, and the other developed from callus produced by mature seeds, have yielded protoplasts capable of regenerating plants when using cells of the Calrose 76 suspension as a nurse culture. In addition, protoplasts obtained from three-week-old primary callus of immature embryos of IR54 were capable of regenerating plants when using the same culture conditions. PMID- 24212900 TI - Organization of cortical microtubules and microfibril deposition in response to blue-light-induced apical swelling in a tip-growing Adiantum protonema cell. AB - The arrangements of cortical microtubules (MTs) in a tip-growing protonemal cell of Adiantum capillus-veneris L. and of cellulose microfibrils (MFs) in its wall were examined during blue-light (BL)-induced apical swelling. In most protonemal cells which had been growing in the longitudinal direction under red light, apical swelling was induced within 2 h of the onset of BL irradiation, and swelling continued for at least 8 h. During the longitudinal growth under red light, the arrangement of MFs around the base of the apical hemisphere (the subapical region) was perpendicular to the cell axis, while a random arrangement of MFs was found at the very tip, and a roughly axial arrangement was observed in the cylindrical region of most cells. This orientation of MFs corresponds to that of the cortical MTs reported previously (Murata et al. 1987, Protoplasma 141, 135 138). In cells irradiated with BL, a random rather than transverse arrangement of both MTs and MFs was found in the subapical region. Time-course studies showed that this reorientation occurred within 1 h after the onset of the BL irradiation, i.e. it preceded the change in growth pattern. These results indicate that the orientation of cortical MTs and of cellulose MFs is involved in the regulation of cell diameter in a tip-growing Adiantum protonemal cell. PMID- 24212901 TI - Comparative biochemical and immunological studies of the glycine betaine synthesis pathway in diverse families of dicotyledons. AB - Members of the Chenopodiaceae can accumulate high levels (>100 MUmol.(g DW)(-1)) of glycine betaine (betaine) in leaves when salinized. Chenopodiaceae synthesize betaine by a two-step oxidation of choline (choline->betaine aldehyde-> betaine), with the second step catalyzed by betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8). High betaine levels have also been reported in leaves of species from several distantly-related families of dicotyledons, raising the question of whether the same betaine-synthesis pathway is used in all cases.Fast atom bombardment mass spectrometry showed that betaine levels of >100 MUmol.(g DW)(-1) are present in Lycium ferocissimum Miers (Solanaceae), Helianthus annuus L. (Asteraceae), Convolvulus arvensis L. (Convolvulaceae), and Amaranthus caudatus L. (Amaranthaceae), that salinization promotes betaine accumulation in these plants, and that they can convert supplied choline to betaine aldehyde and betaine. Nicotiana tabacum L. and Lycopersicon lycopersicum (L.) Karst. ex Farw. (Solanaceae), Lactuca sativa L. (Asteraceae) and Ipomoea purpurea L. (Convolvulaceae) also contained betaine, but at a low level (0.1-0.5 MUmol.(g DW)(-1). Betaine aldehyde dehydrogenase activity assays, immunotitration and immunoblotting demonstrated that the betaine-accumulating species have a BADH enzyme recognized by antibodies raised against BADH from Spinacia oleracea L. (Chenopodiaceae), and that the Mr of the BADH monomer is in all cases close to 63 000. These data indicate that the choline->betaine aldehyde->betaine pathway may have evolved by vertical descent from an early angiosperm ancestor, and might be widespread (albeit not always strongly expressed) among flowering plants. Consistent with these suggestions, Magnolia x soulangiana was found to have a low level of betaine, and to express a protein of Mr 63 000 which cross-reacted with antibodies to BADH from Spinacia oleracea. PMID- 24212902 TI - Use of antisera to localize callose, xylan and arabinogalactan in the cell-plate, primary and secondary walls of plant cells. AB - Antibodies to cellobiose, L-arabinopyranose, L-arabinofuranose, D-galactose, oligosaccharides containing beta1->4 xylose, oligosaccharides containing beta1->4 glucose, and oligosaccharides containing beta1->3 glucose have been raised in rabbits. The antisera have been characterized to show the specificity of binding to particular polysaccharides. They have been used for immunocytology using the electron microscope to locate the polymers in dividing and differentiating cells of bean (Phaseolus vulgaris L.) root, bean callus tissue and cells of Zinnia elegans L. in vitro. Arabinogalactans have been shown to be present in the cell plate and primary walls but not in secondary thickening. Xylan as distinct from xyloglucan was found in the primary walls but not in the cell-plate. It was present in large amounts in the secondary thickening. Callose was found in the cell plate and also in the young growing wall. In the wall it was specifically located at the plasmodesmata. The use of the antibody against L-arabinofuranose enabled a specific organelle to be detected which was membranous and which occurred within the cytoplasm and also within the vacuole of the cells. Membranes carrying polymers containing L-arabinofuranose were also found in layers just under the plasmamembrane. PMID- 24212903 TI - Relationship between efficiency of photosynthetic energy conversion and chlorophyll fluorescence quenching in upland cotton (Gossypium hirsutum L.). AB - The relationship between components of non-photochemical quenching of chlorophyll fluorescence yield (qNP) and dissipation of excessive excitation energy was determined in cotton leaves using concurrent measurements of fluorescence and gas exchange at 2% and 20% O2 under a range of photon flux densities and CO2 pressures. A nearly stoichiometric relationship was obtained between dissipation of energy not used in photosynthetic CO2 fixation or photorespiration and qNP provided that a component, probably associated with state transitions, was not included in qNP. Although two distinct components of qNP were resolved on the basis of their relaxation kinetics, both components appear effective in energy dissipation. The photon yield of "open" photosystem-II reaction centers decreased linearly with increases in qNP, indicating that much of the energy dissipation occurs in the pigment bed. However, increases in qNP appear dependent on the redox state of these centers. The results are discussed in relation to current hypotheses of the molecular basis of non-radiative energy dissipation. It is concluded that determinations of qNP can provide a quantitative measure of the dissipation of excessive excitation energy if precautions are taken to ensure that the maximum fluorescence yield is measured under conditions that provide complete closure of the photosystem-II reaction centers. It is also concluded that such dissipation can prevent photoinhibitory damage in cotton leaves even under extreme conditions where as much as 80% of the excitation energy is excessive. PMID- 24212904 TI - Effect of increased salinity on CO2 assimilation, O 2 evolution and the delta (13)C values of leaves of Plantago maritima L. developed at low and high NaCl levels. AB - The effect of increased salinity on photosynthesis was studied in leaves of Plantago maritima L. that developed while plants were at low and high NaCl levels. In leaves that developed while plants were grown at 50 mol.m(-3), exposure to 200 and 350 mol.m(-3) NaCl resulted in reductions in net CO2 assimilation and stomatal conductance. The decline in CO2 assimilation in plants at 200 and 350 mol.m(-3) NaCl occurred almost exclusively at high intercellular CO2 concentrations. The initial slope of the CO2 assimilation-intercellular CO2 (A-C i) curve, determined after salinity was increased, was identical or very similar to that measured initially. In contrast to the reductions observed in CO2 assimilation, there were no significant differences in O2 evolution rates measured at 5% CO2 among leaves from plants exposed to higher salinity and plants remaining at low salinity.Leaves that developed while plants were at increased salinity levels also had significantly lower net CO2 assimilation rates than plants remaining at 50 mol.m(-3) NaCl. The lower CO2 assimilation rates in plants grown at 200 and 350 mol.m(-3) NaCl were a result of reduced stomatal conductance and low intercellular CO2 concentration. There were no significant differences among treatments for O2 evolution rates measured at high CO2 levels. The increased stomatal limitation of photosynthesis was confirmed by measurements of the (13)C/(12)C composition of leaf tissue. Water-use efficiency was increased in the plants grown at high salinity. PMID- 24212905 TI - The degrees of polymerization and N-acetylation of chitosan determine its ability to elicit callose formation in suspension cells and protoplasts of Catharanthus roseus. AB - Partially and fully deacetylated chitosan fragments and oligomers were compared for their potency to elicit formation of the 1.3-beta-glucan callose in suspension-cultured cells and protoplasts of Catharanthus roseus (line 385). Chitosan oligomers induced little callose formation, while callose synthesis increased with the degree of polymerization of chitosan up to several thousand corresponding to a molecular mass near 10(6) Da. At a comparable degree of polymerization, partially N-acetylated chitosan fragments were less effective. Colloidal chitin and chitin oligomers induced only trace callose synthesis in protoplasts. These results indicate that the primary interaction involved the amino groups of chitosan and numerous negative charges at the surface of the plasma membrane with spacing in the nanometer range and occurring regularly over micrometer stretches. Charged phospholipid head-groups may fulfill these requirements. The resulting alteration of membrane fluidity may lead to the changes in ion transport known to be associated with the induction of callose formation. PMID- 24212906 TI - Surcose transport in isolated plasma-membrane vesicles from sugar beet (Beta vulgaris L.) Evidence for an electrogenic sucrose-proton symport. AB - An analysis of the molecular mechanism of sucrose transport across the plasmalemma was conducted with isolated plasma-membrane (PM) vesicles. Plasma membrane was isolated by aqueous two-phase partitioning from fully expanded sugar beet (Beta vulgaris L.) leaves. The isolated fraction was predominantly PM vesicles as determined by marker-enzyme analysis, and the vesicles were oriented right-side-out as determined by structurally linked latency of the PM enzyme, vanadate-sensitive Mg(2+)-ATPase. Sucrose uptake was investigated by equilibrating PM vesicles in pH 7.6 buffer and diluting them 20-fold into pH 6.0 buffer. Using this pH-jump technique, vesicles accumulated acetate in a pH dependent, protonophore-sensitive manner, which demonstrated the presence of a pH gradient (DeltapH) across the vesicle membrane. Addition of sucrose to pH-jumped PM vesicles resulted in a pH-dependent, protonophoresensitive uptake of sucrose into the vesicles. Uptake was sucrose-specific in that a 10-fold excess of mannose, glucose, fructose, mannitol, melibiose, lactose or maltose did not inhibit sucrose accumulation. The rate of pH-dependent uptake was saturable with respect of sucrose concentration and had an apparent K m, of 0.45 mM. Sucrose uptake was stimulated approximately twofold by the addition of valinomycin and K(+), which indicated an electrogenic sucrose-H(+) symport. Membrane potentials (DeltaPsi) were imposed across the vesicle membrane using valinomycin and K(+). A membrane potential, negative inside, stimulated pH-dependent sucrose uptake while a DeltaPsi, positive inside, inhibited uptake. Conditions that produce a negative DeltaPsi in the absence of a pH gradient supported, although weakly, sucrose uptake. These data support an electrogenic sucrose-H(+) symport as the mechanism of sucrose transport across the PM in Beta leaves. PMID- 24212907 TI - Mutants of Arabidopsis thaliana with altered phototropism. AB - Thirty five strains of Arabidopsis thaliana (L.) Heynh. have been identified with altered phototropic responses to 450-nm light. Four of these mutants have been more thoroughly characterized. Strain JK224 shows normal gravitropism and "second positive" phototropism. However, while the amplitude for "first positive" phototropism is the same as that in the wild-type, the threshold and fluence for the maximum response in "first positive" phototropism are shifted to higher fluence by a factor of 20-30. This mutant may represent an alteration in the photoreceptor pigment for phototropism. Strain JK218 exhibits no curvature to light at any fluence from 1 MUmol.m(-2) to 2700 MUmol.m(-2), but shows normal gravitropism. Strain JK345 shows no "first positive" phototropism, and reduced gravitropism and "second positive" phototropism. Strain JK229 shows no measurable "first positive" phototropism, but normal gravitropism and "second positive" phototropism. Based on these data, it is suggested that: 1. gravitropism and phototropism contain at least one common element; 2. "first positive" and "second positive" phototropism contain at least one common element; and 3. "first positive" phototropism can be substantially altered without any apparent alteration of "second positive" phototropism. PMID- 24212908 TI - Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber. AB - Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 MUmol.m(-2).s(-1). Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluenceresponse relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response. PMID- 24212909 TI - Gibberellic-acid-stimulated Ca(2+) accumulation in endoplasmic reticulum of barley aleurone: Ca(2+) transport and steady-state levels. AB - The steady-state levels of Ca(2+) within the endoplasmic reticulum (ER) and the transport of (45)Ca(2+) into isolated ER of barley (Hordeum vulgare L. cv. Himalaya) aleurone layers were studied. The Ca(2+)-sensitive dye indo-1. Endoplasmic reticulum was isolated and purified from indo-1-loaded protoplasts, and the Ca(2+) level in the ER was measured using the Ca(2+)-sensitive dye indo 1. Endoplasmic reticulum was isolated and purified from indo-1-loaded protoplasts, and the Ca(2+) level in the lumen of the ER was determined by the fluorescence-ratio method to be at least 3 MUM. Transport of (45)Ca(2+) into the ER was studied in microsomal fractions isolated from aleurone layers incubated in the presence and absence of gibberellic acid (GA3) and Ca(2+). Isopycinic sucrose density gradient centrifugation of microsomal fractions isolated from aleurone layers or protoplasts separates ER from tonoplast and plasma membranes but not from the Golgi apparatus. Transport of (45)Ca(2+) occurs primarily in the microsomal fraction enriched in ER and Golgi. Using monensin and heat-shock treatments to discriminate between uptake into the ER and Golgi, we established that (45)Ca(2+) transport was into the ER. The sensitivity of (45)Ca(2+) transport to inhibitors and the Km of (45)Ca(2+) uptake for ATP and Ca(2+) transport in the microsomal fraction of barley aleurone cells. The rate of (45)Ca(2+) transport is stimulated several-fold by treatment with GA3. This effect of GA3 is mediated principally by an effect on the activity of the Ca(2+) transporter rather than on the amount of ER. PMID- 24212910 TI - Effects of 2,4-dinitrophenol and anoxia on the inorganic-pyrophosphate content of the spadix of Arum maculatum and the root apices of Pisum sativum. AB - This work was done to determine whether the inorganic-pyrophosphate (PPi) content of plant tissues changes when the rate of glycolysis is altered. Treatment of excised clubs of the spadix of Arum maculatum L. and root apices of Pisum sativum L. with 2,4-dinitrophenol increased the rates of respiration but had no detectable effects on PPi contents. When the two tissues were subjected to up to 60 min anoxia, no changes in PPi were detected. Anoxia was shown to lead to a fall in ATP and concomitant rises in ADP and AMP in pea roots. It is argued (i) that variation in the rate of glycolysis was not accompanied by detectable changes in PPi content, (ii) that this observation does not favour the view that pyrophosphate fructose 6-phosphate 1-phosphotransferase mediates appreciable entry into glycolysis, and (iii) that PPi content can be maintained when respiratory-chain phosphorylation is inhibited. PMID- 24212911 TI - One year of hepatitis B immunoglobulin plus tenofovir therapy is safe and effective in preventing recurrent hepatitis B post-liver transplantation. AB - BACKGROUND: Hepatitis B immunoglobulin (HBIG) given in combination with a nucleos(t)ide analogue has reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation (LT); however, the most effective protocol remains unclear. OBJECTIVE: To evaluate the use of tenofovir disoproxil fumarate (TDF) in combination with one year of low-dose HBIG. METHODS: Twenty four adults who underwent LT for HBV-related liver disease at the University Health Network (Toronto, Ontario) and received TDF (+/- lamivudine) and one year of HBIG to prevent recurrent HBV infection from June 2005 to June 2011 were evaluated. RESULTS: The median length of follow-up post-LT was 29.1 months. Three patients died during the follow-up period. Patient survival was 100% and 84.1% at one and five years, respectively. None of the patients developed recurrent HBV infection. No significant adverse event was observed due to TDF administration; renal function pre- and post-LT were also acceptably preserved. CONCLUSION: The present study demonstrated that a short, finite course of low-dose HBIG combined with maintenance of long-term TDF staring before LT is cost-effective and safe. However, further prospective study involving a larger patient cohort with a longer follow-up period is required to confirm the results. PMID- 24212912 TI - Endoscopic transmural necrosectomy for walled-off pancreatic necrosis: a systematic review and meta-analysis. AB - BACKGROUND: Endoscopic transmural necrosectomy (ETN) is emerging as a viable treatment option for walled-off pancreatic necrosis. This NOTES-type procedure is significantly less invasive than an extensive surgical debridement; however, published data regarding the success of ETN in treating pancreatic necrosis have varied. OBJECTIVE: To evaluate the published medical literature to determine the success of treating walled-off pancreatic necrosis with ETN. METHODS: Studies using ETN as a primary mode of therapy to treat organized pancreatic necrosis were selected. Success was defined as resolution of the necrotic cavity proven by radiology. Articles were searched in Medline, PubMed, Ovid journals, CINAH, old Medline, Medline nonindexed citations and the Cochrane controlled trials registry. The summary estimates were expressed as pooled proportions. First, the individual study proportions were transformed into a quantity using Freeman-Tukey variant of the arcsine square root transformed proportion. The pooled proportion was calculated as the back-transform of the weighted mean of the transformed proportions, using inverse arcsine variance weights for the fixed-effects model and DerSimonian-Laird weights for the random-effects model. Publication bias was calculated using the Begg-Mazumdar and Harbord bias estimators. RESULTS: The initial search identified 920 reference articles, of which 129 relevant articles were selected and reviewed. Data were extracted from eight studies (n=233) that met the inclusion criteria. Organization of pancreatic necrosis was determined by computed tomography scan in all of the studies. The mean time of ETN after onset of acute pancreatitis/abdominal pain was seven weeks. The weighted mean size of the necrotic cavity was 12.87 cm (95% CI 10.54 cm to 15.20 cm). The weighted mean number of endoscopic procedures needed to resolve the necrotic cavity was 4.09 (95% CI 2.31 to 5.87). Pooled proportion of successful resolution of pancreatic necrosis using ETN was 81.84% (95% CI 76.73% to 86.44%). The pooled proportion of recurrence in the form of necrotic cavity or pseudocyst after ETN was 10.88% (95% CI 7.27% to 15.11%). Complications were noted in 21.33% (95% CI 16.40% to 26.72%) of patients and included bleeding, sepsis and perforation. The weighted mean number of days in hospital after ETN was 32.85 days (95% CI 10.50 to 55.20 days). For pancreatic necrosis that did not resolve, surgery had to be performed in 12.98% (95% CI 9.05% to 17.51%) of patients. The fixed-effect model was used to report all of the pooled proportions. Estimates calculated using fixed- and random-effects models were similar. Test of heterogeneity yielded P>0.10, indicating that the studies could be combined. The publication bias calculated using Begg-Mazumdar bias indicator yielded a Kendall's tau b value of -0.07 (P=0.72) and the same using Harbord bias indicator gave a value of 0.33 (95% CI 1.35 to 2.01; P=0.60). Both of these indicators show that there was no publication bias. CONCLUSION: The present meta-analysis showed that ETN is safe and effective at treating patients with symptomatic walled-off necrosis. ETN offers the advantage of minimally invasive endoscopic treatment without transabdominal surgery; however, better techniques and equipment are still needed to improve procedural efficiency. Decisions to perform ETN should be made by advanced endoscopists in collaboration with a multidisciplinary team with the facilities and personnel to manage these complex patients. PMID- 24212913 TI - A survey of perceptions and practices of complementary alternative medicine among Canadian gastroenterologists. AB - BACKGROUND: Despite a high prevalence of complementary alternative medicine (CAM) use among inflammatory bowel disease (IBD) patients, there is a dearth of information about the attitudes and perceptions of CAM among the gastroenterologists who treat these patients. OBJECTIVE: To characterize the beliefs, perceptions and practices of gastroenterologists toward CAM use in patients with IBD. METHODS: A web-based survey was sent to member gastroenterologists of the Canadian Association of Gastroenterology. The survey included multiple-choice and Likert scale questions that queried physician knowledge and perceptions of CAM and their willingness to discuss CAM with patients. RESULTS: Fifty-three per cent of respondents considered themselves to be IBD subspecialists. The majority (86%) of gastroenterologists reported that less than one-half of their patient population had mentioned the use of CAM. Only 8% of physicians reported initiating a conversation about CAM in the majority of their patient encounters. Approximately one-half (51%) of respondents were comfortable with discussing CAM with their patients, with lack of knowledge being cited as the most common reason for discomfort with the topic. Most gastroenterologists (79%) reported no formal education in CAM. While there was uncertainty as to whether CAM interfered with conventional medications, most gastroenterologists believed it could be effective as an adjunct treatment. CONCLUSION: Our findings demonstrate that gastroenterologists were hesitant to initiate discussions about CAM with patients. Nearly one-half were uncomfortable or only somewhat comfortable with the topic, and most may benefit from CAM educational programs. Interestingly, most respondents appeared to be receptive to CAM as adjunct therapy alongside conventional IBD treatment. PMID- 24212914 TI - Chronic hepatitis C in Western Canada: a survey of practice patterns among gastroenterologists in Alberta and British Columbia. AB - OBJECTIVE: To survey gastroenterologists in British Columbia and Alberta with regard to awareness of chronic hepatitis C virus (HCV) management and practice patterns among physicians who treat and do not treat HCV-infected patients. METHODS: An anonymous two-page mail survey was distributed to actively practicing adult gastroenterologists in British Columbia and Alberta. Among physicians who treated HCV patients, respondents answered assessment of fibrosis pretreatment, measurement of rapid virological response, prescription of protease inhibitors (PIs), barriers to using these agents and referral patterns. For those who did not treat HCV, referral of patients for treatment and to whom was assessed. RESULTS: Seventy-seven of 166 individuals completed the survey (46% response rate). Most (49%) practiced in academic or large community (42%) settings. Chronic liver disease comprised <25% of individual practice in 71%. Forty-eight (62%) treated HCV and two-thirds prescribed a PI. Barriers to prescription included unfamiliarity (six of 16), lack of allied health (five of 16) and few suitable patients (seven of 16). Pretreatment liver biopsy was performed by 33% (16 of 48) and 69% (33 of 48) used noninvasive measures. Rapid virological response was measured in 83% (40 of 48). Referral patterns changed in 46% (22 of 48) of physicians who treated HCV. All respondents who did not treat HCV referred patients for consideration, with 90% (26 of 29) made to hepatologists. CONCLUSIONS: Chronic liver disease comprised <25% of practice in the majority of surveyed respondents. Among those who treated HCV, one-third have not prescribed a PI. Barriers to prescription and referral pattern changes are noted by those currently treating patients with HCV infection. PMID- 24212915 TI - Single-dose infliximab in hepatitis C genotype 1 treatment-naive patients with high serum tumour necrosis factor-alpha does not influence the efficacy of pegylated interferon alpha-2b/ribavirin therapy. AB - BACKGROUND: Serum tumour necrosis factor-alpha (TNF-alpha) levels correlate negatively with hepatitis C virus (HCV) antiviral response. OBJECTIVES: To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR). METHODS: The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1 infected patients 18 to 65 years of age with high serum TNF-alpha values (>300 pg/mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg/kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon alpha2b (1.5 MUg/kg/week) plus weight-based ribavirin (800 mg/day to 1400 mg/day) for up to 48 weeks. RESULTS: Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon alpha2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0-2 = 79%, F3-4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted. CONCLUSION: A single infliximab dose before pegylated-interferon alpha2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR. PMID- 24212916 TI - Suppression of SCIN inhibits human prostate cancer cell proliferation and induces G0/G1 phase arrest. AB - SCIN is a calcium regulated actin severing and capping protein. Its homologue in zebrafish is found to be related with cell death. In the present study, we found that SCIN is highly expressed in human prostate cancer specimens. However, the functions of SCIN in human prostate carcinoma cells are largely unknown. To address the function of SCIN in prostate carcinoma cells, we used lentivirus mediated RNAi to knock down SCIN expression in PC3 cells, a prostate carcinoma cell line. We found that in vitro silencing of SCIN could inhibit the proliferation and colony formation ability of PC3 cells. Furthermore, cell cycle analysis showed that reduced SCIN expression lead to G0/G1 cell cycle arrest through the regulation of cell cycle-related genes, such as p21Waf1/Cip1, cyclin dependent kinase inhibitor 2A (CDKN2A, p16Ink4A) and cyclin A2. These results suggest that SCIN plays an important role in the proliferation of prostate cancer cells and lentivirus-mediated inhibition of SCIN expression may be a potential therapeutic method for the treatment of prostate cancer. PMID- 24212917 TI - Lawton IADL scale in dementia: can item response theory make it more informative? AB - BACKGROUND: impairment of functional abilities represents a crucial component of dementia diagnosis. Current functional measures rely on the traditional aggregate method of summing raw scores. While this summary score provides a quick representation of a person's ability, it disregards useful information on the item level. OBJECTIVE: to use item response theory (IRT) methods to increase the interpretive power of the Lawton Instrumental Activities of Daily Living (IADL) scale by establishing a hierarchy of item 'difficulty' and 'discrimination'. METHODS: this cross-sectional study applied IRT methods to the analysis of IADL outcomes. Participants were 202 members of the Scottish Dementia Research Interest Register (mean age = 76.39, range = 56-93, SD = 7.89 years) with complete itemised data available. RESULTS: a Mokken scale with good reliability (Molenaar Sijtsama statistic 0.79) was obtained, satisfying the IRT assumption that the items comprise a single unidimensional scale. The eight items in the scale could be placed on a hierarchy of 'difficulty' (H coefficient = 0.55), with 'Shopping' being the most 'difficult' item and 'Telephone use' being the least 'difficult' item. 'Shopping' was the most discriminatory item differentiating well between patients of different levels of ability. CONCLUSIONS: IRT methods are capable of providing more information about functional impairment than a summed score. 'Shopping' and 'Telephone use' were identified as items that reveal key information about a patient's level of ability, and could be useful screening questions for clinicians. PMID- 24212918 TI - Frailty status can be accurately assessed using inertial sensors and the TUG test. AB - BACKGROUND: frailty is an important geriatric syndrome linked to increased mortality, morbidity and falls risk. METHODS: a total of 399 community-dwelling older adults were assessed using Fried's frailty phenotype and the timed up and go (TUG) test. Tests were quantified using shank-mounted inertial sensors. We report a regression-based method for assessment of frailty using inertial sensor data obtained during TUG. For comparison, frailty was also assessed using the same method based on grip strength and manual TUG time. RESULTS: using inertial sensor data, participants were classified as frail or non-frail with mean accuracy of 75.20% (stratified by gender). Using TUG time alone, frailty status was classified correctly with mean classification accuracy of 71.82%. Similarly, using grip strength alone, the frailty status was classified correctly with mean classification accuracy of 77.65%. Stratifying sensor data by gender yielded significantly (p<0.05) increased accuracy in classifying frailty when compared with equivalent manual TUG time-based models. CONCLUSION: results suggest that a simple protocol involving assessment using a well-known mobility test (Timed Up and Go (TUG)) and inertial sensors can be a fast and effective means of automatic, non-expert assessment of frailty. PMID- 24212919 TI - Parental longevity is associated with cognition and brain ageing in middle-aged offspring. AB - BACKGROUND: offspring of long-lived individuals have lower risk for dementia. We examined the relation between parental longevity and cognition and subclinical markers of brain ageing in community-dwelling adult offspring. METHODS: offspring participants with both parents in the Framingham Heart Study, aged >=55 years and dementia-free underwent baseline and repeat neuropsychological (NP) testing and brain magnetic resonance imaging (MRI). Parental longevity was defined as having at least one parent survive to age >=85 years. To test the association between parental longevity and measures of cognition and brain volumes, we used multivariable linear and logistic regression adjusting for age, sex, education and time to NP testing or brain MRI. RESULTS: of 728 offspring (mean age 66 years, 54% women), 407 (56%) had >=1 parent achieve longevity. In cross-sectional analysis, parental longevity was associated with better scores on attention (beta 0.21 +/- 0.08, P = 0.006) and a lower odds of extensive white matter hyperintensity on brain MRI (odds ratio 0.59, 95% CI: 0.38, 0.92, P = 0.019). The association with white matter hyperintensity was no longer significant in models adjusted for cardiovascular risk factors and disease. In longitudinal analysis (6.7 +/- 1.7 years later), offspring with parental longevity had slower decline in attention (0.18 +/- 0.08, P = 0.038), executive function (beta 0.19 +/- 0.09, P = 0.031) and visual memory (beta -0.18 +/- 0.08, P = 0.023), and less increase in temporal horn volume (beta -0.25 +/- 0.09, P = 0.005). The associations persisted in fully adjusted models. CONCLUSION: parental longevity is associated with better brain ageing in middle-aged offspring. PMID- 24212920 TI - Effect of music-based multitask training on cognition and mood in older adults. AB - BACKGROUND: in a secondary analysis of a randomised controlled trial, we investigated whether 6 months of music-based multitask training had beneficial effects on cognitive functioning and mood in older adults. METHODS: 134 community dwellers aged >=65 years at increased risk for falling were randomly assigned to either an intervention group (n = 66) who attended once weekly 1-h supervised group classes of multitask exercises, executed to the rhythm of piano music, or a control group with delayed intervention (n = 68) who maintained usual lifestyle habits, for 6 months. A short neuropsychological test battery was administered by an intervention-blinded neuropsychologist at baseline and Month 6, including the mini-mental state examination (MMSE), the clock-drawing test, the frontal assessment battery (FAB) and the hospital anxiety (HADS-A) and depression scale. RESULTS: intention-to-treat analysis showed an improvement in the sensitivity to interference subtest of the FAB (adjusted between-group mean difference (AMD), 0.12; 95% CI, 0.00 to 0.25; P = 0.047) and a reduction in anxiety level (HADS-A; AMD, -0.88; 95% CI, -1.73 to -0.05; P = 0.039) in intervention participants, as compared with the controls. Within-group analysis revealed an increase in MMSE score (P = 0.004) and a reduction in the number of participants with impaired global cognitive performance (i.e., MMSE score <=23; P = 0.003) with intervention. CONCLUSION: six months of once weekly music-based multitask training was associated with improved cognitive function and decreased anxiety in community-dwelling older adults, compared with non-exercising controls. Studies designed to further delineate whether training-induced changes in cognitive function could contribute to dual-task gait improvements and falls reduction, remain to be conducted. PMID- 24212921 TI - Rice- and butterfly-wing effect inspired self-cleaning and low drag micro/nanopatterned surfaces in water, oil, and air flow. AB - In search of new solutions to complex challenges, researchers are turning to living nature for inspiration. For example, special surface characteristics of rice leaves and butterfly wings combine the shark skin (anisotropic flow leading to low drag) and lotus leaf (superhydrophobic and self-cleaning) effects, producing the so-called rice and butterfly wing effect. In this paper, we study four microstructured surfaces inspired by rice leaves and fabricated with photolithography techniques. We also present a method of creating such surfaces using a hot embossing procedure for scaled-up manufacturing. Fluid drag, self cleaning, contact angle, and contact angle hysteresis data are presented to understand the role of sample geometrical dimensions. Conceptual modeling provides design guidance when developing novel low drag, self-cleaning, and potentially antifouling surfaces for medical, marine, and industrial applications. PMID- 24212922 TI - The role of bacterial surface and substratum hydrophobicity in adhesion ofLeptospira biflexa serovarpatoc 1 to inert surfaces. AB - Adhesion of the hydrophilicLeptospira biflexa serovarpatoc 1 (L. patoc) was consistently greater on inert hydrophobic surfaces than on hydrophilic surfaces (glass and plastic). When inert substrata were coated with fetal calf serum (FCS) or bovine serum albumin fraction V (BSA), however, surface hydrophobicity was reduced compared to untreated surfaces, but adhesion ofL. patoc increased. The mechanism of adhesion at protein-coated surfaces is likely to be different than that at untreated surfaces, but it is suggested that the adhesion is nonspecific, as the level of adhesion is similar for different protein coatings. Increased adhesion to FCS- and BSA-coated surfaces was apparently not associated with substrate utilization (scavenging of fatty acids) from the coatings, as essentially fatty acid-free BSA-coated surfaces had similar levels of adhesion. The presence of FCS in the diluent lowered the adhesion ofL. patoc regardless of the original nature of the substratum. This may result from the mutual repulsion of the bacterium and the substratum caused by the exclusion volumes of similar macromolecules adsorbed to both surfaces from the FCS solution. PMID- 24212923 TI - Nutritional strategy of a benthic filamentous bacterium. AB - Filibacter limicola is a filamentous gliding bacterium isolated from the profundal sediment of a eutrophic lake. It is an obligate amino acid utilizer. The kinetic parameters for the metabolism of four amino acids byF. limicola, Vitreoscilla spp. and the bacterial populations of water and sediment samples were compared.F. limicola exhibited low half-saturation constants (K) which were of the same order as those obtained with water samples. The K values for theVitreoscilla spp. and the sediment were an order of magnitude higher. It would appear that the bacterium is a specialist, inhabiting a niche which is sufficiently nutrient rich to support an organism with a limited substrate range. It also possesses a high affinity uptake system for some amino acids which may permit it to compete effectively during periods of nutrient depletion. PMID- 24212924 TI - Methods and sources for the enrichment and isolation of budding, nonprosthecate bacteria from freshwater. AB - Methods are described for the observation, enrichment and isolation (from various freshwater samples) of bacteria of the generaPlanctomyces andPirella. Because immature buds were easily dislodged by shearing forces, slide culture techniques and direct microscopy of the budding process are recommended. An "auxanographic" technique to detect possible stimulation by soluble substrates was based on the diffusion of these substrates from peripherally placed crystals into the agar of a slide culture. Nearly every water sample investigated contained representatives of the generaPlanctomyces, Pirella, andBlastobacter, as well as budding cocci. Six enrichment techniques were tried; some enrichment experiments lasted several months. Allowing samples without added substrate to stand for a long time or generally employing nutrient-poor media were most successful. The "petri dish method," taking advantage of attachment of many budding bacteria to glass surfaces, was especially useful for increasing the numbers ofPlanctomyces spp. Pure cultures obtained from freshwater samples were tentatively placed in the generaPlanctomyces, Pirella, andBlastobacter. One strain appeared to represent a new genus of gram-positive, budding, and nonprosthecate bacteria. PMID- 24212925 TI - Interactions among cellulolytic bacteria from an anaerobic digester. AB - High cellulolytic activity of particular strains did not cause dominance of one, or a few, species of fiber-digesting bacteria in a cattlewaste anaerobic digester. The population contained a large number of species and varieties with different cellulolytic and fiber-digesting activities. Although mixed cultures of some of these bacteria showed no intereffects, with others, cellulolysis was less or in some cases greater than that shown by individual components of the cultures. The interactions were probably related to effects on growth of the bacteria rather than on activities of components of the cellulase enzyme complex, and culture filtrates of two of the more numerous cellulolytic species ofClostridium affected growth of other cellulolytic bacteria. The inhibitory factor(s) appeared to be of bacteriocin type, but the stimulatory factor(s) was unknown. It was suggested that these interactions are localized or short-lived in the digester, and so the population remains in a "dynamic" steady state.Some inhibitions of growth of rumen cellulolytic bacteria were caused by the digester bacteria, but it was suggested that factors other than these inhibitions are responsible for the absence of rumen bacteria from anaerobic digesters. PMID- 24212926 TI - Modeling of the evolution of bacterial densities in an eutrophic ecosystem (sewage lagoons). AB - The process of wastewater treatment was studied by modeling the relationships between physical, chemical, and biological (bacteria, phytoplankton, zooplankton) components of the sewage treatment lagoons of an urban wastewater center, based upon a two-year sampling program. The models of interactions between variables were tested by path analysis. The path coefficients were computed from the results of ridge regression, instead of linear multiple regression. The results show that fecal coliforms were effectively controlled by the environmental variables included in the model, which have a cyclic seasonal behavior. This control grew stronger with distance from the input (R (2)=0.71) to the output (R (2)=0.88) of the treatment plant, resulting in effective elimination of most enteric bacteria. Simultaneously, the ecosystem's community of aerobic heterotrophic bacteria became more independent from the model's predictive variables, with increased distance from the sewage input, thus demonstrating its maturation as an autonomous community in the lagoon ecosystem. Consequences of modeling are discussed, with respect to the understanding of biological wastewater treatment mechanisms and ecosystem dynamics and to plant management. PMID- 24212927 TI - PTEN, here, there, everywhere. PMID- 24212928 TI - Bim vanishes in the light of a mitotic Aurora. PMID- 24212929 TI - PPARgamma needs a helping hand to make fat. PMID- 24212930 TI - When numbers matters: mitochondrial DNA and gliomagenesis. PMID- 24212933 TI - Non-invasive mapping of organ perfusion and blood flow by CT and MRI highlighted by a case of pulmonary artery stenosis. PMID- 24212931 TI - The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. AB - The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein coding and non-coding transcripts that are likely regulated by its members. PMID- 24212932 TI - A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons. AB - The mechanisms governing neuron death following NGF deprivation are incompletely understood. Here, we show that Trib3, a protein induced by NGF withdrawal, has a key role in such death via a loop involving the survival kinase Akt and FoxO transcription factors. Trib3 overexpression is sufficient to induce neuron death, and silencing of endogenous Trib3 strongly protects from death when NGF is withdrawn. Mechanism studies reveal that Trib3 interferes with phosphorylation/activity of Akt and contributes to Akt inactivation after NGF deprivation. FoxO1a, a direct Akt substrate, is dephosphorylated upon NGF withdrawal and consequently undergoes nuclear translocation and activates pro apoptotic genes. We find that Trib3 is required for FoxO1a dephosphorylation and nuclear translocation after NGF deprivation. Conversely, Trib3 induction requires FoxO transcription factors, which show enhanced occupancy of the Trib3 promoter region following NGF withdrawal. Collectively, these findings support a mechanism in which NGF deprivation, Akt dephosphorylation/inactivation, FoxO dephosphorylation/activation and Trib3 induction are linked in a self-amplifying feed-forward loop that culminates in neuron death. PMID- 24212934 TI - Tumor Necrosis Factor (TNF) and Chemokines in Colitis-Associated Cancer. AB - The connection between inflammation and tumorigenesis has been well established, based on a great deal of supporting evidence obtained from epidemiological, pharmacological, and genetic studies. One representative example is inflammatory bowel disease, because it is an important risk factor for the development of colon cancer. Moreover, intratumoral infiltration of inflammatory cells suggests the involvement of inflammatory responses also in other forms of sporadic as well as heritable colon cancer. Inflammatory responses and tumorigenesis activate similar sets of transcription factors such as NF-kB, Stat3, and hypoxia inducible factor and eventually enhances the expression of inflammatory cytokines including tumor necrosis factor (TNF) and chemokines. The expression of TNF and chemokines is aberrantly expressed in a mouse model of colitis-associated carcinogenesis as well as in inflammatory bowel disease and colon cancer in humans. Here, after summarizing the presumed actions of TNF and chemokines in tumor biology, we will discuss the potential roles of TNF and chemokines in chronic inflammation associated colon cancer in mice. PMID- 24212935 TI - Microarray analysis in a cell death resistant glioma cell line to identify signaling pathways and novel genes controlling resistance and malignancy. AB - Glioblastoma multiforme (GBM) is a lethal type of cancer mainly resistant to radio- and chemotherapy. Since the tumor suppressor p53 functions as a transcription factor regulating the expression of genes involved in growth inhibition, DNA repair and apoptosis, we previously assessed whether specific differences in the modulation of gene expression are responsible for the anti tumor properties of a dominant positive p53, chimeric tumor suppressor (CTS)-1. CTS-1 is based on the sequence of p53 and designed to resist various mechanisms of inactivation which limit the activity of p53. To identify CTS-1-regulated cell death-inducing genes, we generated a CTS-1-resistant glioma cell line (229R). We used Affymetrix whole-genome microarray expression analysis to analyze alterations in gene expression and identified a variety of CTS-1 regulated genes involved in cancer-linked processes. 313 genes were differentially expressed in Adeno-CTS-1 (Ad-CTS-1)-infected and 700 genes in uninfected 229R cells compared to matching parental cells. Ingenuity Pathway Analysis (IPA) determined a variety of differentially expressed genes in Ad-CTS-1-infected cells that were members of the intracellular networks with central tumor-involved players such as nuclear factor kappa B (NF-kappaB), protein kinase B (PKB/AKT) or transforming growth factor beta (TGF-beta). Differentially regulated genes include secreted factors as well as intracellular proteins and transcription factors regulating not only cell death, but also processes such as tumor cell motility and immunity. This work gives an overview of the pathways differentially regulated in the resistant versus parental glioma cells and might be helpful to identify candidate genes which could serve as targets to develop novel glioma specific therapy strategies. PMID- 24212936 TI - Prediction of metastasis and recurrence in colorectal cancer based on gene expression analysis: ready for the clinic? AB - Cancers of the colon and rectum, which rank among the most frequent human tumors, are currently treated by surgical resection in locally restricted tumor stages. However, disease recurrence and formation of local and distant metastasis frequently occur even in cases with successful curative resection of the primary tumor (R0). Recent technological advances in molecular diagnostic analysis have led to a wealth of knowledge about the changes in gene transcription in all stages of colorectal tumors. Differential gene expression, or transcriptome analysis, has been proposed by many groups to predict disease recurrence, clinical outcome, and also response to therapy, in addition to the well established clinico-pathological factors. However, the clinical usability of gene expression profiling as a reliable and robust prognostic tool that allows evidence-based clinical decisions is currently under debate. In this review, we will discuss the most recent data on the prognostic significance and potential clinical application of genome wide expression analysis in colorectal cancer. PMID- 24212937 TI - Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133. AB - Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells. PMID- 24212938 TI - Nanotechnology-based detection and targeted therapy in cancer: nano-bio paradigms and applications. AB - The application of nanotechnology to biomedicine, particularly in cancer diagnosis and treatment, promises to have a profound impact on healthcare. The exploitation of the unique properties of nano-sized particles for cancer therapeutics is most popularly known as nanomedicine. The goals of this review are to discuss the current state of nanomedicine in the field of cancer detection and the subsequent application of nanotechnology to treatment. Current cancer detection methods rely on the patient contacting their provider when they feel ill, or relying on non-specific screening methods, which unfortunately often result in cancers being detected only after it is too late for effective treatment. Cancer treatment paradigms mainly rely on whole body treatment with chemotherapy agents, exposing the patient to medications that non-specifically kill rapidly dividing cells, leading to debilitating side effects. In addition, the use of toxic organic solvents/excipients can hamper the further effectiveness of the anticancer drug. Nanomedicine has the potential to increase the specificity of treatment of cancer cells while leaving healthy cells intact through the use of novel nanoparticles. This review discusses the use of nanoparticles such as quantum dots, nanoshells, nanocrystals, nanocells, and dendrimers for the detection and treatment of cancer. Future directions and perspectives of this cutting-edge technology are also discussed. PMID- 24212941 TI - Sputum-based molecular biomarkers for the early detection of lung cancer: limitations and promise. AB - Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers. PMID- 24212940 TI - Mechanisms and therapeutic implications of cell death induction by indole compounds. AB - Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3'-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics. PMID- 24212942 TI - beta-Catenin Is a Positive Regulator of Estrogen Receptor-alpha Function in Breast Cancer Cells. AB - Estrogen receptor-alpha (ERalpha) is a key factor in the development of breast cancer in humans. The expression and activity of ERalpha is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between beta-catenin and ERalpha in human breast cancer cells. Knockdown of beta catenin by RNAi resulted in significant reduction of ERalpha mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERalpha target genes pS2 and GREB1. In addition beta-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. beta-catenin and ERalpha could not be co-immunoprecipitated by ERalpha antibodies from lysates of E2-treated or untreated cells suggesting lack of direct physical interaction. It is concluded that beta-catenin is a positive regulator of ERalpha mRNA and protein expression. PMID- 24212939 TI - Immune suppression in tumors as a surmountable obstacle to clinical efficacy of cancer vaccines. AB - Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies. PMID- 24212943 TI - Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis. AB - Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-kappaB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis. PMID- 24212944 TI - Dual targeting of the insulin-like growth factor and collateral pathways in cancer: combating drug resistance. AB - The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF 1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas. PMID- 24212945 TI - Immunotherapy for urothelial carcinoma: current status and perspectives. AB - Intravesical instillation of bacillus Calmette Guerin (BCG) for the treatment of urothelial carcinoma (UC) of the bladder is based on the BCG-induced immune response, which eradicates and prevents bladder cancer. The results of recent studies have suggested that not only major histocompatibility complex (MHC) nonrestricted immune cells such as natural killer cells, macrophages, neutrophils, etc., but also MHC-restricted CD8+ T cells play an important role and are one of the main effectors in this therapy. Better understanding of the mechanism of BCG immunotherapy supports the idea that active immunotherapy through its augmented T cell response can have great potential for the treatment of advanced UC. In this review, progress in immunotherapy for UC is discussed based on data from basic, translational and clinical studies. We also review the escape mechanism of cancer cells from the immune system, and down-regulation of MHC class I molecules. PMID- 24212947 TI - Toll-like receptor 4 signaling integrates intestinal inflammation with tumorigenesis: lessons from the murine model of colitis-associated cancer. AB - Chronic inflammation has long been implicated as a predisposition for cancer, but the underlying mechanism for how this occurs has remained obscure. Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine which is known to be highly linked to colorectal cancer. During chronic inflammation the intestinal mucosa is in a constant cycle of injury and repair resulting in aberrant epithelial proliferation, a process that increases the risk of neoplastic transformation. In particular, the coexistence of commensal flora in the intestine plays an important role in the regulation of mucosal restitution after epithelial injury. It has become apparent that signaling through toll-like receptors (TLRs), the receptor family recognizing pathogen-associated molecular patterns, is crucial to intestinal epithelial proliferation and mucosal restitution. We have recently described two important downstream pathways underlying TLR4-mediated epithelial proliferation in a mouse model of colitis associated cancer; i.e., cyclooxygenase 2 (COX-2)-mediated production of prostaglandin E2 (PGE2), and induction of specific ligands for epidermal growth factor receptor (EGFR). These two pathways are closely involved with mucosal levels of PGE2 and other prostanoids such as 15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2). Understanding the fine interplay between the TLR signaling and intestinal tumorigenesis in the setting of chronic inflammation can contribute to establishing a novel treatment strategy for inflammation-associated cancers. PMID- 24212946 TI - Natural and Induced Humoral Responses to MUC1. AB - MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer. PMID- 24212949 TI - Current perspectives on desmoid tumors: the mayo clinic approach. AB - Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation. PMID- 24212948 TI - Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. AB - Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments. PMID- 24212950 TI - Upregulation of leukotriene receptors in gastric cancer. AB - BACKGROUND: Leukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5 lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC). METHODS: The expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT 1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa. RESULTS: Male-to-female ratio was 24:11. The median age was 70 years (range 34-91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88-97%) and in tumor-free specimens as well (89-100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test). CONCLUSIONS: LTB4 receptors and CysLT-1 are up regulated in GC tissue implying a role in gastric carcinogenesis. PMID- 24212951 TI - C-type Lectin Receptors for Tumor Eradication: Future Directions. AB - Dendritic cells are key regulators in directing immune responses and therefore are under extensive research for the induction of anti-tumor responses. DCs express a large array of receptors by which they scan their surroundings for recognition and uptake of pathogens. One of the receptor-families is the C-type lectins (CLR), which bind carbohydrate structures and internalize antigens upon recognition. Intracellular routing of antigen through CLR enhances loading and presentation of antigen through MHC class I and II, inducing antigen-specific CD4+ and CD8+ T-cell proliferation and skewing T-helper cells. These characteristics make CLRs very interesting targets for DC-based immunotherapy. Profound research has been done on targeting specific tumor antigens to CLR using either antibodies or the natural ligands such as glycan structures. In this review we will focus on the current data showing the potency of CLR-targeting and discuss improvements that can be achieved to enhance anti-tumor activity in the near future. PMID- 24212952 TI - Inflammatory alterations of the extracellular matrix in the tumor microenvironment. AB - Complex interactions between cancer cells and host stromal cells result in the formation of the "tumor microenvironment", where inflammatory alterations involve the infiltration of tumor-associated fibroblasts and inflammatory leukocytes that contribute to the acquisition of malignant characteristics, such as increased cancer cell proliferation, invasiveness, metastasis, angiogenesis, and avoidance of adaptive immunity. The microenvironment of a solid tumor is comprised not only of cellular compartments, but also of bioactive substances, including cytokines, growth factors, and extracellular matrix (ECM). ECM can act as a scaffold for cell migration, a reservoir for cytokines and growth factors, and a signal through receptor binding. During inflammation, ECM components and their degraded fragments act directly and indirectly as inflammatory stimuli in certain cases and regulate the functions of inflammatory and immune cells. One such ECM component, hyaluronan, has recently been implicated to modulate innate immune cell function through pattern recognition toll-like receptors and accelerate the recruitment and activation of tumor-associated macrophages in inflamed cancers. Here, we will summarize the molecular mechanism linking inflammation with ECM remodeling in the tumor microenvironment, with a particular emphasis on the role of hyaluronan in controlling the inflammatory response. PMID- 24212953 TI - Inflammation-related carcinogenesis and prevention in esophageal adenocarcinoma using rat duodenoesophageal reflux models. AB - Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing. PMID- 24212954 TI - Chimeric DNA Vaccines against ErbB2+ Carcinomas: From Mice to Humans. AB - DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities. PMID- 24212956 TI - Assessment of the evolution of cancer treatment therapies. AB - Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present. PMID- 24212955 TI - Aberrant signaling pathways in glioma. AB - Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12-15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies. PMID- 24212957 TI - Therapeutic approaches to target cancer stem cells. AB - The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC. PMID- 24212959 TI - Treatment of extra - abdominal desmoid tumors with chemotherapy. AB - Fibromatosis, or extra-abdominal desmoid tumor, is a benign disease which often has an aggressive clinical course that can be difficult to treat. We performed a retrospective review of 16 patients (12 females and four males) with a mean age of 34.2 years treated with methotrexate and vinblastine for newly diagnosed or recurrent extra-abdominal desmoid tumor. The mean age of our patient cohort was 34.2 years (range 11-70), and the mean tumor size was 11.5 cm (range 2.5-21.2 cm). The mean duration of therapy was 12 months with an average follow-up of 43 months (range 1-149 months). Fourteen of 16 patients demonstrated a clinical response to treatment. Eight of 14 patients demonstrated a radiologic decrease in tumor size. Only one patient progressed on therapy. Six patients developed recurrent symptoms after discontinuation of treatment. Chemotherapy-related symptoms including neutropenia, nausea, and vomiting were common and observed in most patients, however these side effects were mild and transient. Five patients developed peripheral neuropathy that prompted a change from vinblastine to vinorelbine during treatment. One potentially life-threatening complication (pneumocystis pneumonia) occurred which was diagnosed early and successfully treated. The use of methotrexate and vinblastine/vinorelbine in the management of fibromatosis appears to be an effective treatment with minimal treatment-related side effects. PMID- 24212958 TI - Novel antibody-based proteins for cancer immunotherapy. AB - The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future. PMID- 24212960 TI - Microvessel Density Is Associated with VEGF and alpha-SMA Expression in Different Regions of Human Gastrointestinal Carcinomas. AB - Tumor angiogenesis is known to be regulated by growth factors secreted by host and tumor cells. Despite the importance of tumor vasculature and angiogenic heterogeneity in solid tumors, few studies have compared the vasculature in different regions of human cancer. Blood vessels from different regions of carcinomas might have morphofunctional implications in tumor angiogenesis. In the present study, therefore, we have examined the relationship between microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression and alpha smooth muscle actin (alpha-SMA) expression in the center of the tumor (CT), periphery (P) and metastasis (M) regions from gastrointestinal carcinomas (GITC), as well as the association of MVD with clinicopathological factors. Surgically resected specimens corresponding to the CT, P and M from 27 patients were examined for FVIII, VEGF and alpha-SMA by immunohistochemistry. The MVD was not significantly different in the CT, P and M regions from GITC. The MVD in the VEGF positive group was significantly higher than in the VEGF negative group (CT, p = 0.034; P, p = 0.030; M, p = 0.032). The MVD as a function of alpha-SMA expression was also significantly higher in the CT and P region compared to the M region (p = 0.0008). In conclusion, the MVD association with VEGF and alpha-SMA expression, might indicate an increase of the number of neoformed and preexisting blood vessels uniformly or partially covered by pericytes in different regions of GITC, suggesting that not only MVD and VEGF are important parameters to the tumor vasculature, but also blood vessels maturation is a crucial factor for gastrointestinal tumor angiogenesis regulation and possible target of vascular therapy. PMID- 24212961 TI - Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre. AB - PURPOSE: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. METHODS AND MATERIALS: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5-8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8 years post treatment. RESULTS: All patients completed radiotherapy without any treatment breaks. The 8-year risks of >= Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of >= Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. CONCLUSIONS: These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting. PMID- 24212962 TI - Scalpel or SABR for Treatment of Early-Stage Lung Cancer: Clinical Considerations for the Multidisciplinary Team. AB - Treatment options for early-stage (T1-2 N0) non-small cell lung cancer are often limited by the patient's advanced age, poor performance status, and comorbidities. Despite these challenges, stereotactic ablative radiotherapy (SABR) provides a highly effective and safe therapy for intrathoracic tumors and has become the standard of care for delivering definitive treatment in medically inoperable patients. High-quality treatment, which includes reliable immobilization, accurate tumor targeting, and precise verification of dose delivery, is essential both to achieve successful cure and to avoid debilitating toxicities. Generally, SABR is well tolerated in patients with peripherally located tumors, but even centrally or superiorly located lesions can be treated if there is adequate conformal avoidance of normal structures and/or modified fractionation to meet dose constraints. While several preliminary studies suggest that SABR is as efficacious as surgery in operable patients, results of randomized data will illuminate whether the indications for SABR can be expanded to include patients who are candidates for surgical resection. Herein, we review the rationale for using SABR and its application in treating different patient populations with early-stage lung cancer. PMID- 24212963 TI - Phase II Study of Pomalidomide in Patients with Castration-Resistant Prostate Cancer. AB - BACKGROUND: Pomalidomide is a distinct immunomodulatory agent that also displays anti-proliferative and proapoptotic activity. The purpose of this study was to assess the efficacy and safety of pomalidomide for the treatment of chemotherapy naive patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Pomalidomide was administered orally in doses of 1 or 2 mg/day without interruption. Follow ups were conducted every 4 weeks with evaluation of study outcomes at 12 weeks. The principal study outcomes were PSA response, time to progression (TTP) using RECIST, overall survival (OS), and safety. A total of 32 patients were enrolled: 15 in the 1 mg/day cohort (median baseline PSA level of 12.30 ng/mL [0.8-236.0]), and 17 in the 2 mg/day cohort (median baseline PSA level of 12.50 ng/mL [0.6-191.8]). RESULTS: In the 1 mg cohort disease was stabilized for >=28 days in eight patients, and median TTP was 2.90 months. In the 2 mg cohort, PSA decreased >50% in three patients, disease was stabilized for >=28 days in seven patients, and median TTP was 5.87 months. Toxicity in both cohorts was predominantly grade 1 or 2; 2 grade 3 toxicity (fatigue) occurred in the 1 mg cohort, and 5 grade 3 toxicities (chest pain, diarrhea, epigastric pain, impaction, pain) occurred in the 2 mg cohort. One grade 4 toxicity of cardiac ischemia occurred. CONCLUSIONS: Pomalidomide shows promising activity in patients with CRPC and has an acceptable safety profile. PMID- 24212965 TI - Evaluation of Changes in Tumor Shadows and Microcalcifications on Mammography Following KORTUC II, a New Radiosensitization Treatment without any Surgical Procedure for Elderly Patients with Stage I and II Breast Cancer. AB - We introduced non-surgical therapy with a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) into early stages breast cancer treatment. The purpose of this study was to examine changes in tumor shadows and microcalcifications on mammography (MMG) following KORTUC II for elderly patients with breast cancer. We also sought to determine whether MMG was useful in evaluating the therapeutic effect of KORTUC II. In addition to MMG, positron emission tomography-computed tomography (PET-CT) was performed to detect both metastasis and local recurrence. In all 10 patients, tumor shadows on MMG completely disappeared in several months following the KORTUC II treatment. The concomitant microcalcifications also disappeared or markedly decreased in number. Disappearance of the tumors was also confirmed by the profile curve of tumor density on MMG following KORTUC II treatment; density fell and eventually approached that of the peripheral mammary tissue. These 10 patients have so far have also shown neither local recurrence nor distant metastasis on PET-CT with a mean follow-up period of approximately 27 months at the end of September, 2010. We conclude that breast-conservation treatment using KORTUC II, followed by aromatase inhibitor, is a promising therapeutic method for elderly patients with breast cancer, in terms of avoiding any surgical procedure. Moreover, MMG is considered to be useful for evaluating the efficacy of KORTUC II. PMID- 24212964 TI - New Approaches to Immunotherapy for HPV Associated Cancers. AB - Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18). Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP) technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials. PMID- 24212966 TI - An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC). AB - Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research. PMID- 24212968 TI - Efficacy and safety of high-dose-rate brachytherapy of single implant with two fractions combined with external beam radiotherapy for hormone-naive localized prostate cancer. AB - The purpose of this study was to evaluate the efficacy and safety of high-dose rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naive prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c-T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15 18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naive localized prostate cancer, and has low GU and GI toxicities. PMID- 24212969 TI - Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression. AB - Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages >=pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy. PMID- 24212967 TI - Epigenetics, nervous system tumors, and cancer stem cells. AB - Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors. PMID- 24212970 TI - Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy. AB - Local tumor recurrence and distant tumor metastasis frequently occur after radiation therapy and result in the death of cancer patients. These problems are caused, at least in part, by a tumor-specific oxygen-poor microenvironment, hypoxia. Oxygen-deprivation is known to inhibit the chemical ionization of both intracellular macro-molecules and water, etc., and thus reduce the cytotoxic effects of radiation. Moreover, DNA damage produced by free radicals is known to be more repairable under hypoxia than normoxia. Hypoxia is also known to induce biological tumor radioresistance through the activation of a transcription factor, hypoxia-inducible factor 1 (HIF-1). Several potential strategies have been devised in radiation therapy to overcome these problems; however, they have not yet achieved a complete remission. It is essential to reveal the intratumoral localization and dynamics of hypoxic/HIF-1-active tumor cells during tumor growth and after radiation therapy, then exploit the information to develop innovative therapeutic strategies, and finally damage radioresistant cells. In this review, we overview problems caused by hypoxia/HIF-1-active cells in radiation therapy for cancer and introduce strategies to assess intratumoral hypoxia/HIF-1 activity. PMID- 24212971 TI - Effects of Surgery and Chemotherapy on Metastatic Progression of Prostate Cancer: Evidence from the Natural History of the Disease Reconstructed through Mathematical Modeling. AB - This article brings mathematical modeling to bear on the reconstruction of the natural history of prostate cancer and assessment of the effects of treatment on metastatic progression. We present a comprehensive, entirely mechanistic mathematical model of cancer progression accounting for primary tumor latency, shedding of metastases, their dormancy and growth at secondary sites. Parameters of the model were estimated from the following data collected from 12 prostate cancer patients: (1) age and volume of the primary tumor at presentation; and (2) volumes of detectable bone metastases surveyed at a later time. This allowed us to estimate, for each patient, the age at cancer onset and inception of the first metastasis, the expected metastasis latency time and the rates of growth of the primary tumor and metastases before and after the start of treatment. We found that for all patients: (1) inception of the first metastasis occurred when the primary tumor was undetectable; (2) inception of all or most of the surveyed metastases occurred before the start of treatment; (3) the rate of metastasis shedding is essentially constant in time regardless of the size of the primary tumor and so it is only marginally affected by treatment; and most importantly, (4) surgery, chemotherapy and possibly radiation bring about a dramatic increase (by dozens or hundred times for most patients) in the average rate of growth of metastases. Our analysis supports the notion of metastasis dormancy and the existence of prostate cancer stem cells. The model is applicable to all metastatic solid cancers, and our conclusions agree well with the results of a similar analysis based on a simpler model applied to a case of metastatic breast cancer. PMID- 24212972 TI - Natural killer T cells subsets in cancer, functional defects in prostate cancer and implications for immunotherapy. AB - Natural killer T cells are T lymphocytes with unique activation and effector properties. The majority of NKT cells, termed type-I or iNKT cells, recognize lipid antigens presented on MHC-like CD1d molecules. Type-I NKT cells have the capacity to rapidly secrete various cytokines upon activation, thereby regulate immune responses exerts dominant anti-tumor and anti-microbial effector functions. Specific activation of type-I NKT cells in mouse models boosts immunity and prevents metastasis, which has led to a number of phase I-II clinical trials. Since the discovery of NKT cells other subsets with different specificities and effector functions have been described. This article briefly reviews the physiological functions of NKT cell subsets, their implications in cancer and the attempts that have been made to employ NKT cells for immune therapy of cancer. PMID- 24212973 TI - The many faces of wnt and pancreatic ductal adenocarcinoma oncogenesis. AB - Pancreatic ductal adenocarcinoma (PDAC) remains amongst the most lethal human cancers. PDAC is characterized by the tumor mass containing a paucity of malignant cells in association with a large desmoplastic reaction comprised of a variety of stromal components. Sporadic PDAC oncogenesis occurs as a result of the sequential acquisition of genetic aberrations occurring in core genetic pathways. Unfortunately, the average PDAC contains a large number of genetic aberrations that are not uniform between individual cancers. The interplay between the complex genetics and stromal component may represent a significant barrier to the development of effective therapy for this disease and ultimately be an important factor in PDAC lethality. The Wnt pathway has been identified as a one of the common pathways undergoing genetic alterations in PDAC. Wnt is a complex signal transduction pathway utilizing both a b-catenin dependent (canonical) and b-catenin independent (noncanonical) signals to affect a wide array of intracellular events. Wnt signal transduction is an integral component of pancreas organogenesis promoting the expansion and development of the exocrine pancreas. Pancreatic cancer may utilize the Wnt signaling pathway in concert with other signaling pathways such as notch during tumorigenesis. This review will focus on the role of Wnt signal transduction in pancreatic cancer biology. PMID- 24212975 TI - Improved nuclear medicine uniformity assessment with noise texture analysis. AB - Because gamma cameras are generally susceptible to environmental conditions and system vulnerabilities, they require routine evaluation of uniformity performance. The metrics for such evaluations are commonly pixel value-based. Although these metrics are typically successful at identifying regional nonuniformities, they often do not adequately reflect subtle periodic structures; therefore, additional visual inspections are required. The goal of this project was to develop, test, and validate a new uniformity analysis metric capable of accurately identifying structures and patterns present in nuclear medicine flood field uniformity images. METHODS: A new uniformity assessment metric, termed the structured noise index (SNI), was based on the 2-dimensional noise power spectrum (NPS). The contribution of quantum noise was subtracted from the NPS of a flood field uniformity image, resulting in an NPS representing image artifacts. A visual response filter function was then applied to both the original NPS and the artifact NPS. A single quantitative score was calculated on the basis of the magnitude of the artifact. To verify the validity of the SNI, an observer study was performed with 5 expert nuclear medicine physicists. The correlation between the SNI and the visual score was assessed with Spearman rank correlation analysis. The SNI was also compared with pixel value-based assessment metrics modeled on the National Electrical Manufacturers Association standard for integral uniformity in both the useful field of view (UFOV) and the central field of view (CFOV). RESULTS: The SNI outperformed the pixel value-based metrics in terms of its correlation with the visual score (rho values for the SNI, integral UFOV, and integral CFOV were 0.86, 0.59, and 0.58, respectively). The SNI had 100% sensitivity for identifying both structured and nonstructured nonuniformities; for the integral UFOV and CFOV metrics, the sensitivities were only 62% and 54%, respectively. The overall positive predictive value of the SNI was 87%; for the integral UFOV and CFOV metrics, the positive predictive values were only 67% and 50%, respectively. CONCLUSION: The SNI accurately identified both structured and nonstructured flood-field nonuniformities and correlated closely with expert visual assessment. Compared with traditional pixel value based analysis, the SNI showed superior performance in terms of its correlation with visual perception. The SNI method is effective for detecting and quantifying visually apparent nonuniformities and may reduce the need for more subjective visual analyses. PMID- 24212974 TI - Emerging cancer vaccines: the promise of genetic vectors. AB - Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost. PMID- 24212976 TI - The translocator protein radioligand 18F-DPA-714 monitors antitumor effect of erufosine in a rat 9L intracranial glioma model. AB - On the one hand, the translocator protein (TSPO) radioligand N,N-diethyl-2-(2-(4 (2-(18)F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ((18)F-DPA-714) has been suggested to serve as an alternative radiotracer to image human glioma, and on the other hand the alkylphosphocholine erufosine (ErPC3) has been reported to induce apoptosis in otherwise highly apoptosis resistant glioma cell lines. The induction of apoptosis by ErPC3 requires TSPO, a mitochondrial membrane protein highly expressed in malignant gliomas. In this preclinical study, we monitored the effect of ErPC3 treatment in vivo using (18)F DPA-714 PET. METHODS: In vitro studies investigated the antitumor effect of ErPC3 in 9L rat gliosarcoma cells. In vivo, glioma-bearing rats were imaged with (18)F DPA-714 for the time of treatment. RESULTS: A significant decrease in 9L cell proliferation and viability and a significant increase in apoptosis and caspase-3 activation were demonstrated on ErPC3 treatment in cell culture. In the rat model, ErPC3 administration resulted in significant changes in (18)F-DPA-714 tumor uptake over the course of the treatment. Immunohistochemistry revealed reduced tumor volume and increased cell death in ErPC3-treated animals accompanied by infiltration of the tumor core by CD11b-positive microglia/macrophages and glial fibrillary acidic protein-positive astrocytes. CONCLUSION: Our findings demonstrate a potent antitumor effect of ErPC3 in vitro, in vivo, and ex vivo. PET imaging of TSPO expression using (18)F-DPA-714 allows effective monitoring and quantification of disease progression and response to ErPC3 therapy in intracranial 9L gliomas. PMID- 24212977 TI - Factors associated with battered Filipino women's decision to stay in or leave an abusive relationship. AB - There is a dearth of research on battered Filipino women's stay or leave decision making process. The present study interviewed 40 battered women in the Philippines to explore factors associated with their decisions to stay or leave their husbands or partners. Results revealed that (a) battered women's decision to stay was associated with intrapersonal and interpersonal factors such as personality characteristics, lack of personal resources, absence of social support, presence of children, length of relationship, and sociocultural factors and (b) battered women's decision to leave their abusive partners was associated with factors such as personality characteristics, personal resources, social support, nature of abuse, and spousal factors. Implications for research and practice were discussed. PMID- 24212978 TI - The relationship of violence and traumatic stress to changes in weight and waist circumference: longitudinal analyses from the study of women's health across the nation. AB - This article investigates the associations of violence and traumatic stress with changes in weight and waist circumference, hypothesizing that violence in midlife would be associated with increases or decreases in weight and waist circumference. The longitudinal cohort of the Study of Women's Health Across the Nation comprised the study sample, which included an ethnically/racially and socially diverse group of 2,870 women between the ages of 42 and 52 years at baseline. Women were followed annually for 10 years, and assessments included weight and waist circumference measures and data on violence, health outcomes, and confounders. At baseline, 8.6% Caucasian, 10.8% African American, 9.2% Chinese, and 5.0% Japanese women reported violence and traumatic stress. Reporting violence and traumatic stress during follow-up was significantly associated with weight gain (odds ratio [OR] = 2.39, 95% confidence interval [CI] = [1.28-4.47]), weight loss (OR = 3.54, 95% CI = [1.73-7.22]), and gain (OR = 2.44, 95% CI = [1.37-4.37]) or loss (OR = 2.66, 95% CI = [1.23-5.77]) in waist circumference, adjusting for age, race/ethnicity, education, marital status, and smoking. Violence and traumatic stress against midlife women were associated with gains or losses in weight and waist circumference. PMID- 24212979 TI - Preliminary investigation of the roles of military background and posttraumatic stress symptoms in frequency and recidivism of intimate partner violence perpetration among court-referred men. AB - Significant rates of intimate partner violence (IPV) perpetration have been identified among men with military backgrounds. Research indicates posttraumatic stress symptoms place military men at increased risk for IPV perpetration, but may be negatively associated with IPV among nonmilitary samples. However, no previous studies have directly compared court-referred IPV offenders with and without military experience, which may have clinical implications if posttraumatic stress symptoms are differentially associated with IPV perpetration across these two samples. Twenty court-referred IPV offenders with military background were demographically matched with 40 court-referred IPV offenders without military background. As anticipated, self- and partner-report of physically assaultive acts and injurious acts during baseline assessment showed significantly greater physical assault and injury perpetrated by offenders with military background. However, 1-year follow-up data on convictions indicated a significantly lower rate of recidivism among offenders with military background than among nonmilitary offenders. As hypothesized, symptoms of posttraumatic stress at intake showed a significant positive correlation with IPV perpetration among offenders with military background; however, this relationship showed a negative correlation among offenders without military background. Clinical implications are discussed including treatment avenues, such as Veterans Courts and other incarceration diversion programs, which may be particularly appropriate for offenders with military backgrounds. PMID- 24212980 TI - Safety and efficacy outcomes of preoperative aspirin in patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. AB - BACKGROUND: The administration of aspirin is traditionally discontinued prior to coronary artery bypass grafting (CABG), given a potential risk of excessive postoperative bleeding. Few studies have previously suggested the benefits of continuing aspirin until the time of surgery. The primary aim of this review is to evaluate the effects of preoperative aspirin therapy on several clinically important outcomes in patients undergoing CABG. METHODS: A meta-analysis of eligible studies of patients undergoing CABG, reporting preoperative aspirin in comparison with no aspirin/placebo and our outcomes, was carried out. The safety outcomes included postoperative bleeding, packed red blood cell (PRBC) transfusion requirements, and reoperation for bleeding. The efficacy outcomes included perioperative myocardial infarction (MI), cerebrovascular accidents (CVAs), and mortality. RESULTS: In 8 randomized controlled trials (RCTs; n = 1538), preoperative aspirin increased postoperative bleeding (difference in means = 132.30 mL; 95 % confidence interval [CI] 47.10-217.51; P = .002), PRBC transfusion requirements (difference in means = 0.67 units; 95% CI 0.10-1.24; P = .02), and reoperation for bleeding (odds ratio [OR] = 1.76; 95% CI 1.05-2.93; P = .03). In 19 observational studies (n = 19551), preoperative aspirin increased postoperative bleeding (difference in means = 132.74 mL; 95% CI 45.77-219.72; P = .003) and PRBC transfusion requirements (difference in means = 0.19 units; 95% CI 0.02-0.35; P = .02) but not reoperation for bleeding (OR = 1.13; 95% CI 0.91 1.42; P = .27). Subgroup analyses for RCTs demonstrated that aspirin given at doses <= 100 mg/d might not increase the postoperative bleeding, and the dose of 325 mg/d might not be a cutoff value that has clinical and statistical significance. No statistically significant differences in the rate of perioperative MI, CVAs, or mortality were seen between the 2 groups. CONCLUSIONS: Preoperative aspirin therapy is associated with increased postoperative bleeding, PRBC transfusion requirements, and reoperation for bleeding in patients undergoing CABG. Doses lower than 100 mg/d may minimize the risk of bleeding. Additional RCTs are needed to assess the effects of preoperative aspirin on the safety and efficacy outcomes in patients undergoing CABG. PMID- 24212981 TI - Lymphatic vessels: new targets for the treatment of inflammatory diseases. AB - The lymphatic system plays an important role in the physiological control of the tissue fluid balance and in the initiation of immune responses. Recent studies have shown that lymphangiogenesis, the growth of new lymphatic vessels and/or the expansion of existing lymphatic vessels, is a characteristic feature of acute inflammatory reactions and of chronic inflammatory diseases. In these conditions, lymphatic vessel expansion occurs at the tissue level but also within the draining lymph nodes. Surprisingly, activation of lymphatic vessel function by delivery of vascular endothelial growth factor-C exerts anti-inflammatory effects in several models of cutaneous and joint inflammation. These effects are likely mediated by enhanced drainage of extravasated fluid and inflammatory cells, but also by lymphatic vessel-mediated modulation of immune responses. Although some of the underlying mechanisms are just beginning to be identified, lymphatic vessels have emerged as important targets for the development of new therapeutic strategies to treat inflammatory conditions. In this context, it is of great interest that some of the currently used anti-inflammatory drugs also potently activate lymphatic vessels. PMID- 24212982 TI - Oral cancer: from bench to bedside, the continuous effort towards better diagnostic, treatment and prognostic tools. PMID- 24212983 TI - Impact of removable partial denture prosthesis on chewing efficiency. AB - Removable partial denture prostheses are still being used for anatomic, medical and economic reasons. However, the impact on chewing parameters is poorly described. OBJECTIVES: The objective of this study was to estimate the impact of removable partial denture prosthesis on masticatory parameters. MATERIAL AND METHODS: Nineteen removable partial denture prosthesis (RPDP) wearers participated in the study. Among them, 10 subjects were Kennedy Class III partially edentulous and 9 with posterior edentulism (Class I). All presented a complete and full dentate opposing arch. The subjects chewed samples of carrots and peanuts with and without their prosthesis. The granulometry of the expectorated boluses from carrot and peanuts was characterized by median particle size (D50), determined at the natural point of swallowing. Number of chewing cycles (CC), chewing time (CT) and chewing frequency (CF=CC/CT) were video recorded. RESULTS: With RPDP, the mean D50 values for carrot and peanuts were lower [Repeated Model Procedures (RMP), F=15, p<0.001] regardless of the type of Kennedy Class. For each food, mean CC, CT and CF values recorded decreased (RMP, F=18, F=9, and F=20 respectively, p<0.01). With or without RPD, the boluses' granulometry values were above the masticatory normative index (MNI) determined as 4,000 um. CONCLUSION: RPDP rehabilitation improves the ability to reduce the bolus particle size, but does not reestablish fully the masticatory function. CLINICAL RELEVANCE: This study encourages the clinical improvement of oral rehabilitation procedure. PMID- 24212984 TI - Importance of a distal proximal contact on load transfer by implant-supported single adjacent crowns in posterior region of the mandible: a photoelastic study. AB - OBJECTIVE: This study aimed to evaluate the importance of a distal proximal contact on the load transfer to the posterior region of the mandible by non splinted adjacent implant-supported crowns using photoelastic stress analysis. MATERIAL AND METHODS: A rectangular model (68x30x15 mm) was made of polymethylmethacrylate resin to simulate half of the mandibular arch. One model was completed with resin replicas representing the first premolar and second molar and with two 3.75 mm dia.x11 mm internal hexagon threaded implants replacing the second premolar and first molar. The other model was manufactured in the same way but without the second molar. Both models were duplicated using photoelastic resin. The roots of the teeth replicas were covered with a layer of polyether impression material to simulate the periodontal ligament. Two different vertical loads were applied to the crowns as follows: 1 - single static point load alternately applied to the crowns replacing the second premolar and first molar (50 N); 2 - simultaneous static point loads applied to both of the crowns replacing the second premolar and first molar (100 N). The resulting isochromatic fringe pattern in the photoelastic model was monitored and photographed. RESULTS: All loading conditions studied showed that the presence of the second molar has changed the load transmission and the pattern of stresses. CONCLUSION: Results showed that the presence of a second molar proximal contact can help minimize the stresses around the implants. PMID- 24212985 TI - Coronal microleakage of endodontically treated teeth with intracanal post exposed to fresh human saliva. AB - OBJECTIVE: The aim of this study was to investigate the coronal microleakage of endodontically treated teeth prepared to receive an intracanal post and teeth with an intracanal post but without a prosthetic crown and exposed to contamination by fresh human saliva. MATERIAL AND METHODS: A mechanical-chemical preparation following the step-back technique was carried out in 35 extracted single-rooted human teeth. The teeth were randomly divided into five groups: G1=root canals instrumented, obturated, and prepared to receive an intracanal post (N=10); G2=root canals with cemented posts but without coronal sealing (N=10); PC1=positive control root canals instrumented and open (N=5); PC2=positive control 2 root canals without instrumentation and open (N=5); and NC=negative control healthy teeth (N=5). The crowns were removed except for the control group of intact teeth. The root canals were obturated and sterilized with cobalt 60 gamma irradiation and were then adapted in an apparatus using a Brain Heart Infusion (BHI) medium and fresh human saliva for contamination. Microbial growth was indicated by the presence of turbidity in the BHI liquid medium. RESULTS: Data were submitted to the Kaplan-Meier Survival Analysis and the Holm Sidak statistic method, which observed an index of 90% of microleakage in root canals after 24 hours for G1 and 70% of microleakage in samples at the end of 40 days for G2. CONCLUSION: The results show that root canals with an intracanal post but without a prosthetic crown can be recontaminated when exposed to fresh human saliva in a short period. PMID- 24212986 TI - Etidronate from medicine to endodontics: effects of different irrigation regimes on root dentin roughness. AB - An increase in dentin roughness, associated with surface composition, contributes to bacterial adherence in recontaminations. Surface roughness is also important for micromechanical interlocking of dental materials to dentin, and understanding the characteristics of the surface is essential to obtain the adhesion of root canal sealers that have different physico-chemical characteristics. OBJECTIVES: To evaluate the effects of sodium hypochlorite (NaOCl), ethylenediaminetetraacetic (EDTA), etidronic (HEBP), and citric acid (CA) associated with different irrigation regimens on root dentin roughness. MATERIAL AND METHODS: Forty-five root halves of anterior teeth were used. The root parts were sectioned in thirds, embedded in acrylic resin and polished to a standard surface roughness. Initially, the samples of each third were randomly assigned into 3 groups and treated as follows: G1 - saline solution (control); G2 - 5% NaOCl+18% HEBP mixed in equal parts; and G3 - 2.5% NaOCl. After initial measuments, the G3 samples were distributed into subgroups G4, G5 and G6, which were subjected to 17% EDTA, 10% CA and 9% HEBP, respectively. Following the new measuments, these groups received a final flush with 2.5% NaOCl, producing G7, G8 and G9. The dentin surface roughness (Ra) was determined before and after treatments using a profilometer. The Wilcoxon test (alpha<0.05) was used to compare the values before and after treatments, and the Friedman test (alpha<0.05) to detect any differences among root thirds. RESULTS: (i) NaOCl did not affect the surface roughness; (ii) there was a significant increase in roughness after the use of chelating agents (P<0.01); and (iii) only the G3 group showed a difference in surface roughness between apical third and other thirds of the teeth (P<0.0043). CONCLUSION: Only the irrigation regimens that used chelating agents altered the roughness of root dentin. PMID- 24212987 TI - Low expression of MSH2 DNA repair protein is associated with poor prognosis in head and neck squamous cell carcinoma. AB - OBJECTIVE: This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients. MATERIAL AND METHODS: Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression. RESULTS: Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p<0.001) and lower MSH2 immunohistochemical expressions (OR=2.943, p=0.032) presented poorer survival for HNSCC by Cox regression models. CONCLUSIONS: Our data demonstrated that lower MSH2 expression might contribute to a higher clinic aggressiveness of HNSCC by promoting an unfavorable outcome. PMID- 24212988 TI - Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial. AB - OBJECTIVE: Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. MATERIAL AND METHODS: In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were recorded before the first and re-entry surgery (six months later): vertical clinical attachment level (VCAL), gingival index (GI), plaque index (PI), horizontal probing depth (HPD), vertical probing depth (VPD), gingival recession (GR), furcation vertical component (FVC), furcation to alveolar crest (FAC), fornix to base of defect (FBD), and furcation horizontal component (FHC) were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant. RESULTS: Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups. CONCLUSION: The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone material. The differences in radiographic changes between the two groups, however, were not statistically significant. PMID- 24212989 TI - Leukotoxicity of Aggregatibacter actinomycetemcomitans in generalized aggressive periodontitis in Brazilians and their family members. AB - OBJECTIVE: The purpose of this study was to examine the leukotoxin promoter types of Aggregatibacter actinomycetemcomitans clones in subjects with generalized aggressive periodontitis (GAgP) and in their family members (FM). MATERIAL AND METHODS: Thirty-five patients with GAgP (33.9+/-7.1 years), 33 of their FM (22.8+/-11.4 years), and 41 patients with chronic periodontitis (CP) (44.1+/-9.4 years) were clinically analyzed using the plaque index, gingival index, probing depth (PD), and clinical attachment level (CAL). Subgingival biofilm samples were collected from four interproximal periodontal sites (>PD and >CAL) of each patient. The presence of A. actinomycetemcomitans and its leukotoxic clone was confirmed by polymerase chain reaction (PCR). RESULTS: A. actinomycetemcomitans was observed in 23 (51.1%) GAgP patients and 16 (30.1%) CP patients. Thirty-seven (94.8%) patients showed minimally leukotoxic strains and 2 (5.1%) showed highly leukotoxic strains. In the FM group, 10 (30.3%) had aggressive periodontitis (AgP), 12 (36.3%) had CP, 11 (33.3%) were periodontally healthy or had gingivitis, and 12.2% were A. actinomycetemcomitans positive. Greater full mouth PD and CAL were observed in GAgP patients positive for the bacteria than those negative for it (p<;0.05), and the presence of A. actinomycetemcomitans positively correlated with GAgP (Odds ratio, 3.1; confidence interval, 1.4-7.0; p=0.009). CONCLUSIONS: The presence of A. actinomycetemcomitans was associated with the clinical condition of GAgP, with most patients exhibiting a generalized form of the disease and minimally leukotoxic clones. Most of the relatives of GAgP patients presented either CP or AgP. PMID- 24212990 TI - Evaluation of the intercanine distance in newborns with cleft lip and palate using 3D digital casts. AB - OBJECTIVE: The purpose of this present study was to compare, by means of 3D digital casts, the anterior transverse dimension of the dental arch of newborns with and without cleft lip and palate. MATERIAL AND METHODS: The sample was composed of ninety-four children aged from 3 to 9 months divided into three study groups: Group I - children without craniofacial deformities (control group); Group II - children with unilateral cleft lip and palate; Group III - children with bilateral cleft lip and palate. Impressions were executed before lip and palate repair in patients with clefts. Dental casts were digitized using a 3D scanner linked to a computer. Measurements of the intercanine distance were measured on the digital casts. Intergroup comparisons were performed using ANOVA (p<0.05). RESULTS: The results showed a mean of 36.5 mm for unilateral cleft lip and palate group, 34.8 mm for bilateral cleft lip and palate group and 27.52 mm for the control group. There was a statistically significant difference between the control group and both groups of patients with cleft lip and palate. There was no statistically significant difference between complete unilateral and bilateral cleft lip and palate groups. CONCLUSIONS: Patients with complete cleft lip and palate were born with an increased anterior dimension of the maxillary dental arch compared to non cleft patients. PMID- 24212991 TI - Bone remodeling at microscrew interface near extraction site in the beagle dog mandible-histologic and immunohistochemical analyses. AB - Extraction is often used as part of orthodontic therapy, and good control of anchorage is a key step after extraction. Although microscrews can be implanted close to the extraction site in order to achieve orthodontic support, the efficiency of bone remodeling at the implant-bone interface near the extraction region is dubious. OBJECTIVE: The purpose of this study was to investigate bone remodeling of the bone-microscrew interface near the tooth extraction site, in the absence of loading. MATERIAL AND METHODS: Third and fourth premolars were extracted from the mandibles of beagle dogs, followed by placement of test microscrews near the extraction sites. Control microscrews were placed further away from the extraction site. All samples were collected after 1, 3, 8, or 12 weeks of healing following extraction. The bone remodeling process at the interface was evaluated using histologic and immunohistochemical analyses. RESULTS: Initially, a large number of inflammatory cells were aggregated at the interface. The expression levels of core binding factor (Cbfa1), osteocalcin (OC) and transforming growth factor beta (TGF-beta) were inconspicuous in both groups, whereas tumor necrosis factor alpha (TNF-alpha) was strongly expressed, especially in the test groups (P<0.05). Subsequently, the expression levels of Cbfa1, OC and TGF-beta were found to increase significantly, and active osteogenesis was observed. CONCLUSIONS: During week 1, inflammatory reaction is a major concern at the bone-microscrew interface near the extraction site. However, with healing, the influence of extraction on the remodeling of bone surrounding the microscrews decreases, thus facilitating successful treatment. PMID- 24212992 TI - Evaluation of bond strength of silorane and methacrylate based restorative systems to dentin using different cavity models. AB - OBJECTIVE: The aim of this in vitro study was to evaluate the microtensile bond strength (uTBS) to dentin of two different restorative systems: silorane-based (P90), and methacrylate-based (P60), using two cavity models. MATERIAL AND METHODS: Occlusal enamel of 40 human third molars was removed to expose flat dentin surface. Class I cavities with 4 mm mesial-distal width, 3 mm buccal lingual width and 3 mm depth (C-factor=4.5) were prepared in 20 teeth, which were divided into two groups (n=10) restored with P60 and P90, bulk-filled after dentin treatment according to manufacturer's instructions. Flat buccal dentin surfaces were prepared in the 20 remaining teeth (C-factor=0.2) and restored with resin blocks measuring 4x3x3 mm using the two restorative systems (n=10). The teeth were sectioned into samples with area between 0.85 and 1.25 mm2 that were submitted to uTBS testing, using a universal testing machine (EMIC) at speed of 0.5 mm/min. Fractured specimens were analyzed under stereomicroscope and categorized according to fracture pattern. Data were analyzed using ANOVA and Tukey Kramer tests. RESULTS: For flat surfaces, P60 obtained higher bond strength values compared with P90. However, for Class I cavities, P60 showed significant reduction in bond strength (p<0.05). No statistical difference between restorative systems was shown for Class I cavity model (p>0.05), or between Class I Cavity and Flat Surface group, considering P90 restorative system (p>0.05). Regarding fracture pattern, there was no statistical difference among groups (p=0.0713) and 56.3% of the fractures were adhesive. CONCLUSION: It was concluded that methacrylate-based composite uTBS was influenced by cavity models, and the use of silorane-based composite led to similar bond strength values compared to the methacrylate-based composite in cavities with high C-factor. PMID- 24212993 TI - Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single oral pathology service during an 8-year period. AB - Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. OBJECTIVE: The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. MATERIAL AND METHODS: All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. RESULTS: A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004). CONCLUSIONS: The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients. PMID- 24212994 TI - Wizard CD Plus and ProTaper Universal: analysis of apical transportation using new software. AB - OBJECTIVE: This study has two aims: 1) to evaluate the apical transportation of the Wizard CD Plus and ProTaper Universal after preparation of simulated root canals; 2) to compare, with Adobe Photoshop, the ability of a new software (Regeemy) in superposing and subtracting images. MATERIAL AND METHODS: Twenty five simulated root canals in acrylic-resin blocks (with 20o curvature) underwent cone beam computed tomography before and after preparation with the rotary systems (70 kVp, 4 mA, 10 s and with the 8*8 cm FoV selection). Canals were prepared up to F2 (ProTaper) and 24.04 (Wizard CD Plus) instruments and the working length was established to 15 mm. The tomographic images were imported into iCAT Vision software and CorelDraw for standardization. The superposition of pre- and post-instrumentation images from both systems was performed using Regeemy and Adobe Photoshop. The apical transportation was measured in millimetres using Image J. Five acrylic resin blocks were used to validate the superposition achieved by the software. Student's t-test for independent samples was used to evaluate the apical transportation achieved by the rotary systems using each software individually. Student's t-test for paired samples was used to compare the ability of each software in superposing and subtracting images from one rotary system per time. RESULTS: The values obtained with Regeemy and Adobe Photoshop were similar to rotary systems (P>0.05). ProTaper Universal and Wizard CD Plus promoted similar apical transportation regardless of the software used for image's superposition and subtraction (P>0.05). CONCLUSION: Wizard CD Plus and ProTaper Universal promoted little apical transportation. Regeemy consists in a feasible software to superpose and subtract images and appears to be an alternative to Adobe Photoshop. PMID- 24212995 TI - Abrasion of 6 dentifrices measured by vertical scanning interference microscopy. AB - OBJECTIVES: The abrasion of dentifrices is well recognized to eliminate the dental plaque. The aims of this study were to characterize the abrasive powders of 6 dentifrices (3 toothpastes and 3 toothpowders) and to measure the abrasion on a test surface by Vertical Scanning Interference microscopy (VSI). MATERIAL AND METHODS: Bright field and polarization microscopy were used to identify the abrasive particles on the crude dentifrices and after prolonged washes. Scanning electron microscopy and microanalysis characterized the shape and nature of the particles. Standardized and polished blocks of poly(methylmethacrylate) were brushed with a commercial electric toothbrush with the dentifrices. VSI quantified the mean roughness (Ra) and illustrated in 3D the abraded areas. RESULTS: Toothpastes induced a limited abrasion. Toothpowders induced a significantly higher roughness linked to the size of the abrasive particles. One powder (Gencix(r) produced a high abrasion when used with a standard testing weight. However, the powder is based on pumice particles covered by a plant homogenate that readily dissolves in water. When used in the same volume, or after dispersion in water, Ra was markedly reduced. CONCLUSION: Light and electron microscopy characterize the abrasive particles and VSI is a new tool allowing the analysis of large surface of abraded materials. PMID- 24212996 TI - The modified Ottawa method to establish the update need of a systematic review: glass-ionomer versus resin sealants for caries prevention. AB - OBJECTIVE: To demonstrate the application of the modified Ottawa method by establishing the update need of a systematic review with focus on the caries preventive effect of GIC versus resin pit and fissure sealants; to answer the question as to whether the existing conclusions of this systematic review are still current; to establish whether a new update of this systematic review was needed. METHODS: Application of the Modified Ottawa method. Application date: April/May 2012. RESULTS: Four signals aligned with the criteria of the modified Ottawa method were identified. The content of these signals suggest that higher precision of the current systematic review results might be achieved if an update of the current review were conducted at this point in time. However, these signals further indicate that such systematic review update, despite its higher precision, would only confirm the existing review conclusion that no statistically significant difference exists in the caries-preventive effect of GIC and resin-based fissure sealants. CONCLUSION: In conclusion, this study demonstrated the modified Ottawa method as an effective tool in establishing the update need of the systematic review. In addition, it was established that the conclusions of the systematic review in relation to the caries preventive effect of GIC versus resin based fissure sealants are still current, and that no update of this systematic review was warranted at date of application. PMID- 24212997 TI - Mandibular metastasis of adenocarcinoma from prostate cancer: case report according to epidemiology and current therapeutical trends of the advanced prostate cancer. AB - Prostate cancer represents the most frequent non-cutaneous neoplasia in males. This type of neoplasia can develop peculiar patterns of evolution, presenting, in many cases, precocious relapses and metastasis. Bone metastasis in the mouth is extremely rare, and represents 1% of all malignant mouth neoplasias. The aim of the present study is to report a clinical case of bone metastasis in the mandibular region associated with a tumoral prostate adenocarcinoma, as well as to discuss connected aspects about diagnosis, prognosis and integrated treatment of this condition. PMID- 24212999 TI - Inorganic arsenic induces apoptosis through downregulation of Ube2d genes and p53 accumulation in rat proximal tubular cells. AB - Ube2d ubiquitin-conjugating enzymes promote p53 ubiquitination and proteasomal degradation. We previously showed that cadmium induced p53-dependent apoptosis through the suppression of expression of Ube2d family genes (Ube2d1, Ube2d2, Ube2d3 and Ube2d4) in normal rat proximal tubular cells. Here we examined the effects of inorganic arsenic and inorganic mercury, which induce apoptosis in proximal tubular cells, on cellular protein level of p53 and gene expression of Ube2d family. Inorganic arsenic induced apoptosis with p53 accumulation, and suppressed Ube2d1, Ube2d2 and Ube2d4 expression, but not Ube2d3. On the other hand, although apoptosis was induced in response to inorganic mercury in proximal tubular cells, protein level of p53 was not elevated by inorganic mercury. These results suggest that inorganic arsenic, but not inorganic mercury, may induce p53 dependent apoptotic pathways through downregulation of gene expression of Ube2d family in proximal tubular cells. PMID- 24213000 TI - Knockdown of the gene for homeobox protein HOXB13 reduces toxicity of oxidative stress inducers in HEK293 cells. AB - HEK293 cells transfected with a double-stranded siRNA to suppress expression of the homeobox gene HOXB13 were highly resistant to oxidative stress-inducing agents, such as hydrogen peroxide, N-ethylmaleimide (NEM), and paraquat. This finding suggests that HOXB13 might enhance cell injury caused by oxidative stress. PMID- 24212998 TI - Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development. AB - Eosinophilia is a hallmark characteristic of T helper type 2 (TH2) cell associated diseases and is critically regulated by the central eosinophil growth factor interleukin 5 (IL-5). Here we demonstrate that IL-5 activity in eosinophils was regulated by paired immunoglobulin-like receptors PIR-A and PIR B. Upon self-recognition of beta2-microglobulin (beta2M) molecules, PIR-B served as a permissive checkpoint for IL-5-induced development of eosinophils by suppressing the proapoptotic activities of PIR-A, which were mediated by the Grb2 Erk-Bim pathway. PIR-B-deficient bone marrow eosinophils underwent compartmentalized apoptosis, resulting in decreased blood eosinophilia in naive mice and in mice challenged with IL-5. Subsequently, Pirb(-/-) mice displayed impaired aeroallergen-induced lung eosinophilia and induction of lung TH2 cell responses. Collectively, these data uncover an intrinsic, self-limiting pathway regulating IL-5-induced expansion of eosinophils, which has broad implications for eosinophil-associated diseases. PMID- 24213001 TI - Methylmercury induces caspase-dependent apoptosis and autophagy in human neural stem cells. AB - Methylmercury (MeHg) is a well-known human neurotoxic agent whose exposure sources are mainly environmental and aquatic-derived food. MeHg is reported to induce central nervous system disability. However, the exact mechanism of MeHg induced neurotoxicity is still unknown. In this study, to investigate which cell death signaling pathway is related with MeHg-induced cytotoxicity, the effects of MeHg on apoptosis and autophagy were evaluated in HB1.F3 human neural stem cells (NSCs). Human NSCs were treated with 1 MUM of MeHg for 48 hr and the effect of MeHg on cell signaling pathway was elucidated. MeHg inhibited Akt1/mTOR signaling that led to induction of caspase-dependent apoptosis and autophagy in the NSCs. Furthermore, retinoic acid (RA)-induced neuronal differentiation was inhibited by MeHg. Taken together, these results suggest that MeHg inhibits the differentiation of human NSCs by induction of caspase-dependent apoptosis and autophagy. PMID- 24213002 TI - Treatment of mice with 2,3,7,8-Tetrachlorodibenzo-p-dioxin markedly increases the levels of a number of cytochrome P450 metabolites of omega-3 polyunsaturated fatty acids in the liver and lung. AB - We previously reported that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increased the levels of several cytochrome P450 metabolites of the omega-6 polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and linoleic acid in the serum, liver, lung and spleen of C57BL/6 mice in an aryl hydrocarbon receptor (AHR) dependent fashion. These increases correlated with increased levels of CYP1A1, CYP1A2 and/or CYP1B1. In the current study, we measured 77 oxylipins, including 59 that we had not measured previously, and demonstrate that TCDD also markedly increases the levels of many epoxide and diol metabolites of the omega-3 PUFAs, alpha-linolenic acid, eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA) in these mice. Since these epoxide metabolites have been reported to have opposite effects on angiogenesis, tumor growth and tumor metastasis compared with the equivalent metabolites of omega-6 PUFA, these observations have important implications with regard to the potential involvement of the cytochrome P450 metabolites of PUFAs in mediating the biological effects of TCDD and other agonists of AHR. PMID- 24213003 TI - Expression of VEGF-related proteins in cultured human brain microvascular endothelial cells and pericytes after exposure to methylmercury. AB - The localization of neuropathological lesions along deep sulci and fissures is one of the characteristics of a cerebrum damaged by methylmercury. Edematous changes in white matter have been proposed as the cause of the localization of lesions; however, the molecular mechanisms underlying methylmercury-induced edema remain unclear. Since the vascular endothelial growth factor (VEGF) system regulates vascular permeability and can be involved in the progression of edematous changes, we examined the effect of methylmercury on the expression of VEGF-related proteins in cultured human brain microvascular endothelial cells and pericytes. After methylmercury exposure, mRNA and protein levels of VEGF-A in pericytes and placenta growth factor (PlGF) and VEGF-receptor-1/-2 in endothelial cells were elevated. The induction of pericyte VEGF-A expression was independent of hypoxia-inducible factor-alpha and hypoxia-response element signaling. Taken together, these results suggest that methylmercury activates the VEGF system in brain microvessels in a paracrine fashion. When the activation occurs in narrow areas such as along the deep sulci in the cerebrum, hyperpermeability and subsequent edematous changes would cause a circulatory disturbance and result in neural cell damage. We propose this as a reason for the localization of the neuropathological lesions along the deep sulci and fissures in the cerebral cortex, such as the calcarine fissure, in patients with Minamata disease. PMID- 24213004 TI - Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in embryo-fetal development studies--comparative data to Sprague Dawley rats. AB - The purpose of the present study was to collect the background data on Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats in embryo-fetal development studies from the 6 safety research facilities of pharmaceutical companies and contract research organizations. In each facility, 20 or 22 female rats were dosed with vehicle solution during the organogenesis period. As a result, no abnormalities in clinical signs and necropsy findings in dams were found. Body weights and food consumption in dams were lower than those in Sprague Dawley (SD) rats. The number of corpora lutea (13.3 vs. 16.0 in SD) and implantations (11.8 vs. 14.7) were fewer, and fetal body weights (3.66 vs. 3.70) and placental weights (0.42 vs. 0.45) tended to be lower than those in SD rats. Regarding the fetal abnormalities, the incidence of several findings such as the persistent left umbilical artery (10.4% vs. 1.1%) and cervical (5.2% vs. 0.4%), full (7.4% vs. 0.9%) or short supernumerary (64.5% vs. 9.9%) and wavy ribs (6.6% vs. 0.3%) was higher than that in SD rats. Our present study showed that they maintained a sufficient number of live fetuses and the difference in the fetal sex ratio was not observed. In conclusion, Wistar Han rats were considered to be a suitable strain for embryo-fetal development toxicity study. Since the incidence of several abnormalities was higher than that in SD rats, it may be said that to accumulate background control data is important to evaluate the embryo-fetal development toxicity study using Wistar Han rats. PMID- 24213005 TI - Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in general toxicity studies--comparative data to Sprague Dawley rats. AB - The purpose of the present study was to collect background data from repeated dose toxicity studies in Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats with dosing periods of 4, 13 and 26 weeks from four safety research facilities of pharmaceutical companies and contract research organizations participating in the International Genetic Standardization (IGS) rat forum supported by Charles River Laboratories Japan, Inc. The data from Wistar Han rats were compared with those from Sprague Dawley Crl:CD(SD) rats. In addition, the effects of restricted feeding of SD rats were also investigated by one facility. As a result, body weights and food consumption in Wistar Han rats were lower than those of SD rats. White blood cell (WBC), neutrophil, lymphocyte, monocyte and eosinophil counts were almost half of those noted for SD rats and platelet counts were almost 20% less than those in SD rats. Minimal strain differences were noted in several biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase, total cholesterol, triglyceride and phospholipids, and in thymus, ovary and testis weights. Ophthalmologic or histopathologic examinations revealed a higher incidence of corneal opacities or corneal mineralization in Wistar Han rats. Restricted feeding of SD rats resulted in intermediate values for body weights and food consumption between the ad libitum fed SD and Wistar Han rats, and WBC and AST were lower than those in the ad libitum fed SD rats. Based on these results, some strain differences might be ascribable to reduced food consumption and associated body weight changes in Wistar Han rats. PMID- 24213006 TI - Garcinia vilersiana bark extract activates the Nrf2/HO-1 signaling pathway in RAW264.7 cells. AB - Garcinia vilersiana is a traditional medicinal plant in Vietnam. The petroleum ether extract of stem bark of Garcinia vilersiana (GVE) was prepared to evaluate its potential to activate Nrf2, a transcription factor of antioxidant and detoxifying enzymes. Exposure of mouse macrophage RAW264.7 cells to GVE (0.625 2.5 ug/ml) resulted in a significant activation of Nrf2, as evaluated by nuclear accumulation of this transcription factor, and increased antioxidant response element (ARE) binding activity in a time- and concentration-dependent manner. As a result, GVE caused ARE-dependent up-regulation of heme oxygenase-1 (HO-1) in the cells. These results suggest that GVE contains components that have the ability to activate the Nrf2/ARE/HO-1 signaling pathway, leading to cellular protection. PMID- 24213007 TI - Dose-dependent effects of diallyl disulfide on plasma glucose and free fatty acid levels in rats. AB - The acute effects of oral administration of diallyl disulfide (DADS), the major organosulfur compound of garlic, on plasma glucose and free fatty acid (FFA) concentrations were examined in rats. Male, 10-week-old Sprague-Dawley rats were divided into DADS-free and DADS-administered (dose = 10, 20, and 40 mg/kg body weight [BW]) groups. Plasma samples were prepared from whole blood drawn from the tail vein 0, 1, 2, 4, and 6 hr after administration. The stomachs were isolated, and the contents were measured 8 hr after administration. In DADS-administered groups, plasma glucose concentrations were increased in a dose-dependent manner 1 hr after the administration. The increase was transient, except in groups administered 40 mg/kg BW of DADS, in which plasma glucose levels remained significantly higher than the DADS-free levels throughout the experimental period. Similar patterns were observed in the plasma FFA concentrations, although the significant differences were lower than those observed in the plasma glucose concentrations. The gastric contents were dose-dependently elevated after DADS administration. The increase was significant when 20 or 40 mg/kg BW of DADS was administered. These results suggest that oral administration of DADS can mobilize energy substrates into the blood, although a higher dose of DADS slows gastric emptying. PMID- 24213008 TI - Expression and functional characterization of recombinant tributyltin-binding protein type 2. AB - Tributyltin-binding proteins (TBT-bps) are members of the fish lipocalins that were isolated from the blood of Japanese flounder (Paralichthys olivaceus) and function in the binding and detoxification of TBT. In this study, we constructed a baculovirus-silkworm expression system and obtained recombinant TBT-bp2 (rTBT bp2; 31.5 kDa) from the hemolymph of silkworm larvae injected with a recombinant baculovirus containing the TBT-bp2 gene. The binding potential of rTBT-bp2 was investigated and compared to that of the previously available recombinant TBT-bp1 (rTBT-bp1). Both rTBT-bp2 and rTBT-bp1 bound to DAUDA, a typical fluorescent ligand of lipocalins, with dissociation constants of 0.97 and 1.75 uM, respectively. The Hill coefficient value indicated that rTBT-bp2 may have multiple binding sites and strong negative cooperativity. These results suggest that the typical central cavity of lipocalins composed of eight specific beta sheets is conserved in rTBT-bp2, as it is in rTBT-bp1, although rTBT-bp2 has different effects than rTBT-bp1 in TBT binding. In a competition assay, rTBT-bp2 displayed exponential binding affinity to TBT with an inhibition constant of 0.29 uM, demonstrating that TBT binds to the central ligand pocket of rTBT-bp2. However, three fatty acids did not show any affinity to rTBT-bp2. Further studies are required to elucidate the endogenous function of TBT-bps as fish lipocalins and their function in responding to xenobiotics. PMID- 24213009 TI - Effects of pyperonyl butoxide on the female reproductive tract in rats. AB - This study was investigated the effects of piperonyl butoxide (PBO) on the female reproductive tract. Female Crj:Donryu rats were fed a basal diet containing 5,000, 10,000 or 20,000 ppm PBO for 28 days, and compared with food-restricted rats of comparable body weights to those in the PBO 10,000 or 20,000 ppm groups. Although treatment with 20,000 ppm PBO for 28 days depressed body weight gain, the abnormal estrous cyclicity, mainly prolonged diestrus, was also induced by the PBO treatment which was not correlated with body weight change. 20,000 ppm PBO treatment markedly decreased uterine weights and slightly decreased ovarian weights. 10,000 and 20,000 ppm PBO treatment increased liver weights. These cycle and organ weight changes were linked to atrophic uterus and increased atretic follicles in the ovary. In hormone assays, PBO at both doses reduced serum E2 levels, but did not affect corticosterone levels. An anti-uterotrophic assay showed a slight but significant decrease in absolute uterine weight and a reduction of endometrial epithelium height in the 20,000 ppm group. PBO was positive in an ER alpha antagonist reporter gene assay, although the activity was much weaker than that of 4-hydroxytamoxifen. These results indicate that high dose PBO treatment directly induces atrophic changes in the female reproductive tract in rats, and these effects are likely the result of a hypoestrogenic state and the anti-estrogenic activity of PBO. PMID- 24213010 TI - Effects of transovarian exposure to p,p'-DDT and p,p'-DDE on avian reproduction using Japanese quails. AB - In the 1950s to 1970s developed countries reported declines in populations of raptorial and fish-eating birds and dichlorodiphenyltrichloroethane (DDT) and its metabolites were considered causative substances because they accumulated significantly in the tissues of wild birds and animals. However, except for the estrogenic effects of o,p'-DDT, a minor component of commercial DDT, there has been no compelling evidence that DDT directly affects avian reproductive systems. To assess the possible impact of DDT on development and reproduction of birds, exposure experiments to the major component of commercial DDT, p,p'-DDT, and its persistent metabolite, p,p'-dichlorodiphenyldichloroethylene (DDE), were performed using Japanese quail (Coturnix japonica) eggs; the test substances (3 to 100 MUg/g) were injected into the yolk prior to incubation, and hatched chicks were raised to adulthood. p,p'-DDT had no significant effects on the morphology and function of the reproductive systems, although the hatchability of treated eggs was reduced at the highest dose (100 MUg/g). High doses of p,p'-DDE slightly enhanced the eggshell forming ability of female quails; eggshell mass and thickness were increased at 30 MUg/g or more although no morphological changes were observed in the oviduct. Transcriptions of the CYP11A1 gene in the ovaries, and of AHR and ARNT in the livers, of adult females were significantly increased at 3 MUg/g or more of p,p'-DDT. Except for low hatchability, transovarian exposure to p,p'-DDT or p,p'-DDE did not markedly impair the avian reproductive systems, but the hormonal actions of these compounds are likely to change reproductive and hepatic functions even after maturation. PMID- 24213011 TI - Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection. AB - Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo. PMID- 24213012 TI - Global chemokine expression in methylmercury-treated mice: methylmercury induces brain-specific expression of CCL3 and CCL4. AB - We previously reported that methylmercury induces brain-specific upregulation of a chemokine gene, the CCL4 gene. In this study, we investigated the changes in gene expression levels of all chemokines in various tissues (cerebellum, cerebrum, kidney, liver, and spleen) of methylmercury-treated mice. We found that methylmercury induced upregulation of the CCL4 gene and the CCL3 gene, in a brain specific manner. This finding suggests that upregulation of these two chemokine genes mediates selective damage by methylmercury in the central nervous system. PMID- 24213013 TI - Low dose of methylmercury (MeHg) exposure induces caspase mediated-apoptosis in cultured neural progenitor cells. AB - Methylmercury (MeHg) is an environmental pollutant known to cause neurobehavioral defects, and it is especially toxic to the developing brain. In contrast to the adult, the developing brain consists of a large number of dividing neural progenitor cells (NPCs), which are vulnerable targets for MeHg toxicity. In a previous study, we showed that the embryonic NPCs from the telencephalon are more sensitive to MeHg than other neural cells. Here, we investigated the mechanism of cell death underlying MeHg toxicity. We observed that exposure of NPCs to MeHg caused DNA laddering in a dose- and time-dependent manner. Decreased pro-caspase3 and increased cleaved-caspase3 protein was observed 3-12 hours after incubation of NPCs with MeHg. Moreover, the caspase-inhibitor Z-VAD FMK significantly suppressed MeHg-induced cell death in a dose-dependent manner. These results suggest that environmentally relevant levels of MeHg exposure induce apoptosis in NPCs. PMID- 24213014 TI - Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats. AB - Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m3 for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD 2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m3 in male rats and 0.9 mg/m3 in female rats under the present experimental condition. PMID- 24213015 TI - Modulation of tumor necrosis factor-stimulated gene-6 (TSG-6) expression in human endometrium. AB - INTRODUCTION: The human endometrium undergoes repetitive, cyclical changes under the influence of endocrine signals (estrogen and progesterone). In particular, the extensive tissue remodeling, angiogenesis and leukocyte infiltration that occur during decidualization of the endometrium give rise to an environment that is permissive to blastocyst attachment. However, it is now well established that crosstalk (via paracrine signals) between the trophoblast and the endometrium is also a key for successful implantation. Microarray studies have identified TSG-6 as a gene with elevated expression in endometrial stromal cells following the exposure to trophoblast and immune cell products. TSG-6 is an inflammation associated protein which acts as a potent inhibitor of neutrophil extravasation and also plays important roles in matrix remodeling, e.g., by promoting hyaluronan (HA) cross-linking and down-regulating the protease network. Female TSG-6 (-/-) mice are infertile and this has been attributed to their inability to ovulate; however, the importance of TSG-6 in implantation has not been directly investigated. MATERIAL AND METHODS: Real-time PCR, as well as immunofluorescence staining was performed on endometrial biopsies of proliferative and secretory phase samples. In addition stromal cell cultures of human endometrium were used to assess the influence of different stimulating factors on the TSG-6 gene and protein expression via real-time PCR and ELISA. RESULTS: Herein demonstrate that TSG-6 mRNA is expressed by the endometrium during the proliferative and secretory phases of the menstrual cycle. We also show that conditioned media from placental tissues induce rapid upregulation of TSG-6 mRNA expression and sustained protein secretion, with evidence that TNF is an important factor in this effect. Furthermore, we demonstrate changes in protein expression in the mid-secretory phase in women affected by recurrent abortions. CONCLUSION: These data suggest that TSG-6 expression might be essential in endometrial matrix organization and feto-maternal communication during the implantation process. PMID- 24213016 TI - Soluble c-Met expression in the peritoneal fluid and serum of patients with different stages of endometriosis. AB - INTRODUCTION: Hepatocyte growth factor (HGF), also known as scatter factor, and its receptor c-Met have been shown to be implicated in endometriosis. HGF acts as a mitogen, motogen, and morphogen on endometrial epithelial cells. The expression of c-Met on human endometrial cells has been reported. Many proteins are proteolytically released from the surface by a process known as ectodomain shedding. The aim of this study was to determine the levels of soluble c-Met (s cMet) in the peritoneal fluid (PF) and serum samples of patients with different stages of endometriosis. MATERIAL AND METHODS: 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s cMet in the PF and serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant change in the TPC was seen in the serum and PF of patients with endometriosis when compared with normal controls. Results obtained demonstrated that all PF and serum samples presented s-cMet expression, whereas, starting from stages I to IV endometriosis, a significant increase of s-cMet expression was observed as compared to controls. CONCLUSION: The results of this study show that a high expression of s-cMet is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and PF s-cMet may be useful in classifying endometriosis. PMID- 24213017 TI - Patterns of cell elongation in the determination of the final shape in galls of Baccharopelma dracunculifoliae (Psyllidae) on Baccharis dracunculifolia DC (Asteraceae). AB - Cell redifferentiation, division, and elongation are recurrent processes, which occur during gall development, and are dependent on the cellulose microfibrils reorientation. We hypothesized that changes in the microfibrils orientation from non-galled tissues to galled ones occur and determine the final gall shape. This determination is caused by a new tissue zonation, its hyperplasia, and relative cell hypertrophy. The impact of the insect's activity on these patterns of cell development was herein tested in Baccharopelma dracunculifoliae-Baccharis dracunculifolia system. In this system, the microfibrils are oriented perpendicularly to the longest cell axis in elongated cells and randomly in isodiametric ones, either in non-galled or in galled tissues. The isodiametric cells of the abaxial epidermis in non-galled tissues divided and elongated periclinally, forming the outer gall epidermis. The anticlinally elongated cells of the abaxial palisade layer and the isodiametric cells of the spongy parenchyma originated the gall outer cortex with hypertrophied and periclinally elongated cells. The anticlinally elongated cells of the adaxial palisade layer originated the inner cortex with hypertrophied and periclinally elongated cells in young and mature galls and isodiametric cells in senescent galls. The isodiametric cells of the adaxial epidermis elongated periclinally in the inner gall epidermis. The current investigation demonstrates the role of cellulose microfibril reorientation for gall development. Once many factors other than this reorientation act on gall development, it should be interesting to check the possible relationship of the new cell elongation patterns with the pectic composition of the cell walls. PMID- 24213018 TI - Capillary earlobe blood may be used for RNA isolation, gene expression assays and microRNA quantification. AB - An increasing number of studies examining gene expression associated with diseases in children is likely, in the near future, to provide simple and easy to use methods for the isolation of RNA for gene expression profiling. Prerequisites for such studies are likely to encompass the use of small amounts of blood, as well as less invasive blood collection methods. In the current study, RNA was isolated from 20 ul capillary blood samples from the earlobes of 10 adults for quantitative PCR experiments. The results were compared with RNA isolated from venipuncture samples of the 10 samples. The expression of 4 mRNAs and 1 microRNA (miRNA), miRNA-126, was measured. The quantitative PCR results obtained with the capillary blood probes were similar to results using venous blood samples. The few differences observed may result from a variation in the blood cell composition. The use of capillary blood samples from the earlobe for gene expression analysis is likely to allow this method to be used in newborns, babies and children. In addition, such a method, using microliters of blood samples, may also be useful for other medical studies e.g., in cases where repetitive blood sampling is necessary or in patients with bleeding disorders. PMID- 24213019 TI - Associations of PM2.5 constituents and sources with hospital admissions: analysis of four counties in Connecticut and Massachusetts (USA) for persons >= 65 years of age. AB - BACKGROUND: Epidemiological studies have demonstrated associations between short term exposure to PM2.5 and hospital admissions. The chemical composition of particles varies across locations and time periods. Identifying the most harmful constituents and sources is an important health and regulatory concern. OBJECTIVES: We examined pollutant sources for associations with risk of hospital admissions for cardiovascular and respiratory causes. METHODS: We obtained PM2.5 filter samples for four counties in Connecticut and Massachusetts and analyzed them for PM2.5 elements. Source apportionment was used to estimate daily PM2.5 contributions from sources (traffic, road dust, oil combustion, and sea salt as well as a regional source representing coal combustion and other sources). Associations between daily PM2.5 constituents and sources and risk of cardiovascular and respiratory hospitalizations for the Medicare population (> 333,000 persons >= 65 years of age) were estimated with time-series analyses (August 2000-February 2004). RESULTS: PM2.5 total mass and PM2.5 road dust contribution were associated with cardiovascular hospitalizations, as were the PM2.5 constituents calcium, black carbon, vanadium, and zinc. For respiratory hospitalizations, associations were observed with PM2.5 road dust, and sea salt as well as aluminum, calcium, chlorine, black carbon, nickel, silicon, titanium, and vanadium. Effect estimates were generally robust to adjustment by co pollutants of other constituents. An interquartile range increase in same-day PM2.5 road dust (1.71 MUg/m3) was associated with a 2.11% (95% CI: 1.09, 3.15%) and 3.47% (95% CI: 2.03, 4.94%) increase in cardiovascular and respiratory admissions, respectively. CONCLUSIONS: Our results suggest some particle sources and constituents are more harmful than others and that in this Connecticut/Massachusetts region the most harmful particles include black carbon, calcium, and road dust PM2.5. PMID- 24213026 TI - Editorial. PMID- 24213020 TI - Children's recognition of spectrally degraded cartoon voices. AB - OBJECTIVES: Although the spectrally degraded input provided by cochlear implants (CIs) is sufficient for speech perception in quiet, it poses problems for talker identification. The present study examined the ability of normally hearing (NH) children and child CI users to recognize cartoon voices while listening to spectrally degraded speech. DESIGN: In Experiment 1, 5- to 6-year-old NH children were required to identify familiar cartoon characters in a three-alternative, forced-choice task without feedback. Children heard sentence-length utterances at six levels of spectral degradation (noise-vocoded utterances with 4, 8, 12, 16, and 24 frequency bands and the original or unprocessed stimuli). In Experiment 2, child CI users 4 to 7 years of age and a control sample of 4- to 5-year-old NH children were required to identify the unprocessed stimuli from Experiment 1. RESULTS: NH children in Experiment 1 identified the voices significantly above chance levels, and they performed more accurately with increasing spectral information. Practice with stimuli that had greater spectral information facilitated performance on subsequent stimuli with lesser spectral information. In Experiment 2, child CI users successfully recognized the cartoon voices with slightly lower accuracy (0.90 proportion correct) than NH peers who listened to unprocessed utterances (0.97 proportion correct). CONCLUSIONS: The findings indicate that both NH children and child CI users can identify cartoon voices under conditions of severe spectral degradation. In such circumstances, children may rely on talker-specific phonetic detail to distinguish one talker from another. PMID- 24213027 TI - In vitro shoot regeneration from leaf mesophyll protoplasts of hybrid poplar (Populus nigra x P. maximowiczii). AB - Protoplasts were isolated from leaf mesophyll of hybrid poplar (Populus nigra X P. maximowiczii) with a mean yield of 10.4 x 10(6) protoplasts per g fresh weight using 2.0% Cellulase 'Onozuka' R-10, 0.8% Macerozyme R-10, 1.2% Hemicellulase, 2.0% Driselase, and 0.05% Pectolyase Y-23 with CPW salts solution containing 0.6 M mannitol, 0.002 M DTT, 3 mM MES at pH 5.6. A liquid plating method produced the highest frequency of dividing protoplasts (48.6%) using an MS medium without NH4NO3. The highest percent of colony formation was 22.8%, produced with fabric supported semi-solid (0.5% w/v) agar plating method using the same culture medium. Growing cell colonies and/or micro-calli were transferred to a fresh semisolid agar medium containing 0.44 MUM BAP and 9.0 MUM 2,4-D. Multiple shoots were produced from protoplast-derived callus after culture on MS medium containing 6.8 MUM zeatin. After root induction on half-strength MS medium that lacked growth regulators, shoots were transferred to pots containing artificial soil mix. PMID- 24213028 TI - Plant regeneration from callus and protoplast cultures of Helianthus giganteus L. AB - Methods of plant regeneration from callus and protoplasts of Helianthus giganteus L. are described. Embryogenic callus was obtained from leaf explants and plants were regenerated from these calli on MS media with different combinations of benzyladenine and naphtaleneacetic acid. Leaf protoplasts isolated from in vitro grown plants formed somatic embryos when cultured in agarose solidified droplets of V-KM medium containing benzyladenine and naphtaleneacetic acid. Embryos developed into plantlets on media with reduced auxin contents. Regenerated plants were successfully planted in soil. PMID- 24213029 TI - Transformation of Solanum integrifolium poir via Agrobacterium tumefaciens: Plant regeneration and progeny analysis. AB - The wild species Solanum integrifolium represents a source of pest and disease resistance genes for breeding strategies of the cultivated species Solanum melongena. Somatic hybridization via protoplast fusion between the two species may provide a valuable tool for transferring polygenic traits into the cultivated species. The availability of S.integrifolium cells carrying dominant selectable markers would facilitate the heterokaryon rescue. An appropriate methodology for in vitro culture and plant regeneration from leaf explants of S.integrifolium is reported. Efficient leaf-disk transformation via co-cultivation with Agrobacterium tumefaciens led to the regeneration of transformed plants carrying the reporter genes GUS and NPT-II. Transformed individuals were obtained through selection on kanamycin-containing medium. Stable genetic transformation was assessed by histochemical and enzymatic assays for GUS and NPT-II activity, by the ability of leaf disks to initiate callus on Km-containing medium, Southern blot analyses of the regenerated plants, and genetic analysis of their progenies. Selfed-seed progeny of individual transformed plants segregated seedlings capable to root and grow in selective condition, while untransformed progeny did not. Genetic analyses of progeny behaviour showed that the reporter gene NPT-II segregated as single as well as two independent Mendelian factors. In two cases an excess of kanamycin-sensitive seedlings was obtained, not fitting into any genetic hypothesis. PMID- 24213030 TI - Plant regeneration from protoplasts of wheat (Triticum aestivum cv. Hartog). AB - Morphologically normal green plants have reproducibly been regenerated from protoplasts of an Australian wheat (Triticum aestivum cv. Hartog). The protoplasts were isolated from fine embryogenic suspension cultures which were initiated from embryogenic callus. Protoplasts were incubated in a modified liquid MS medium containing half strength of the macroelements, 5 MUm 2,4-D and 0.6 M glucose. Colonies were formed at frequencies ranging from 0.1% to 5%. The frequency of colonies forming fully developed plants varied between 1% and 25%. More than eighty green plants with morphologically normal shoots and roots have been obtained and there was no difficulty in establishing these plants in soil. A cytological study of several randomly selected regenerated plants showed the normal chromosome complement for wheat (2n = 42). PMID- 24213031 TI - Introduction and differential use of various promoters in pollen grains of Nicotiana glutinosa and Lilium longiflorum. AB - As part of our research to develop an alternative system for the transformation of recalcitrant plant species we investigated the use of the male gametophyte as a transformation vector. Therefore the activity of four different promoters (CaMV 35S, LAT52, chiA PA2 and TR2') was analyzed in pollen of a dicot (Nicotiana glutinosa) and a monocot (Lilium longiflorum) plant species. Gene constructs in which the beta-glucuronidase (GUS) gene was placed under the control of these promoters were introduced in pollen using a particle delivery system. No activity of the Cauliflower Mosaic Virus (CaMV) 35S promoter was detected in pollen of both N. glutinosa and L. longiflorum. The promoter of the tomato flower-specific LAT52 gene was highly active in N. glutinosa pollen but remained silent in L. longiflorum pollen. A similar expression pattern was observed for the pollen specific Chalcone Flavanone Isomerase chiA PA2 promoter originally isolated from petunia. The TR2' mannopine synthase promoter of Agrobacterium tumefaciens, however, was active in pollen from Solanaceous species and also in pollen from the monocot L. longiflorum. This suggests that the TR2' promoter is active in vegetative and sporogenous tissues of dicot and monocot plant species. PMID- 24213032 TI - Regeneration of transgenic plants of Prunus armeniaca containing the coat protein gene of Plum Pox Virus. AB - A system was developed which allows the transfer of foreign genes into apricot cultivars. We report the transformation and regeneration of Prunus armeniaca plants with Agrobacterium tumefaciens strain LBA 4404 containing various binary plasmids, pBinGUSint, carrying the marker gene beta-glucuronidase (GUS) and pBinPPVm, carrying the coat protein gene of Plum Pox Virus (PPV). The marker gene GUS was used for optical evaluation of the efficiency of the transformation system. The coat protein gene of PPV was used to introduce coat protein mediated resistance against one of the most important pathogens of stone fruit trees in Europe and the whole Mediterranean area. This is the first report of the successful integration of a viral coat protein gene into a fruit tree species, opening a new perspective on the control of the disease. PMID- 24213033 TI - Coat protein mediated resistance to Plum Pox Virus in Nicotiana clevelandii and N. benthamiana. AB - Transgenic Nicotiana benthamiana and N. clevelandii plants expressing the coat protein of Plum Pox Virus under the control of the 35S promoter from Cauliflower Mosaic Virus were engineered by Agrobacterium tumefaciens mediated transformation. The phenomenon of virus resistance was observed at different levels when transgenic plants, expressing the coat protein and control plants were compared after challenge infection with Plum Pox Virus. N. clevelandii coat protein transgenic plants circumvent virus accumulation. After an initial increase in virus titer similar to the control plants, some coat protein expressing plants showed a reduced accumulation of virus and inhibition of the systemic spread, characterized by decrease of the virus titer and formation of new symptomless leaves. In other N. clevelandii coat protein expressing plants virus accumulation was inhibited and disease symptoms never appeared. N. benthamiana coat protein expressing plants were also protected. After a temporary virus accumulation, virus titer decreased without the appearance of symptoms with the exception of a few plants, which showed a delay of thirty days in the development of symptoms post challenge infection. PMID- 24213034 TI - Effects of some growth regulators on in vitro tuberization in Dioscorea alata L. 'Brazo fuerte' and D. abyssinica Hoch. AB - Nodal cuttings of Dioscorea alata L. 'Brazo fuerte' and D. abyssinica Hoch. were cultured in vitro to assess the influence of NAA on the production of microtubers. In D. alata, high concentrations of NAA (27 and 54 MUM) favored the production of large microtubers, whereas the highest number of microtubers was obtained with 2.7 MUM. D. abyssinica was found to be more sensitive to NAA since concentrations higher than 0.27 MUM promoted the growth of callus on the root system. In this species, the production of the largest microtubers was obtained at 2.7 MUM whereas the number of microtubers was not affected by any concentration tested. In D. alata, the effects of ABA and BAP were also evaluated. The weight of the microtubers increased with increasing concentrations of ABA. This effect, however, was observed only on expiants cultured under 8 h photoperiod, but not on those cultured under 16 h. Finally the presence of BAP at concentrations as low as 0.22 MUM adversely affected the survival of the explants. PMID- 24213035 TI - Callus formation and plant regeneration in standard and microexplants from seedlings of barley (Hordeum vulgare L.). AB - Callus was induced in standard (1 mm) leaf base explants and in cross sections (microexplants) through the seedling axis from seedlings of Hordeum vulgare L.. Reduced callus formation was observed with increasing distance from the leaf base, and explants from the first and second leaves gave the best response. In serial hand sections of the seedling axis frequency of callus formation decreased from 100% in the apical region to 5% in the basal region. Callus formed from all tissues outside the central vascular elements, except for the coleoptile and the scutellum. Plants were regenerated from callus induced from both types of explants. PMID- 24213036 TI - High frequency adventitious shoot regeneration from immature cotyledons of pea (Pisum sativum L.). AB - A procedure has been developed which allows high frequency adventitious shoot regeneration from immature cotyledons of pea. Prolific shoot regeneration occurred following an initial callus growth on a Murashige and Skoog (MS) medium containing 0.5 mg/l 6-benzylaminopurine (BAP) and 4 mg/l alpha-naphthaleneacetic acid (NAA). Cotyledon expiants proximal to the embryonic axis had the highest regeneration potential, however, the presence of an embryonic axis inhibited adventitious shoot regeneration. Addition of silver nitrate (AgNO3) to the medium did not promote the number of regenerated shoots but resulted in shoots with well developed tendrils and large stipules which had a reduced rooting capacity. Regenerated shoots rooted readily (80-90%) in half strength MS medium containing 1 mg/l indole-butyric acid (IBA) and further established well in compost. PMID- 24213037 TI - Expression of PVX coat protein gene under the control of extensin-gene promoter confers virus resistance on transgenic potato plants. AB - Tuber discs of potato (Solanum tuberosum L.) cultivars Desiree and Gracia were infected by Agrobacterium tumefaciens carrying a binary vector with the coat protein gene of potato virus X controlled by the carrot extensin gene long transcript promoter. Several transgenic potato plants have been obtained by direct regeneration of shoots on culture medium with kanamycin used for selection. The presence of the coat protein gene was proved by Southern hybridization in several transformants. Its low but detectable expression level was shown by Northern and Western analysis. Ethephon treatment resulted in a five fold increase in the amounts of the coat protein mRNA. The majority of transformants exhibited reduced accumulation of virus RNA in inoculated leaves. Potentials in the use of an ethylene-inducible promoter in the production of virus-resistant transgenic plants will be discussed. PMID- 24213038 TI - A new organelle related to osmoregulation in ultrarapidly frozenPelvetia embryos. AB - Freeze-fracture electron microscopy of the cortical cytoplasm of unfixed, uncryoprotected, ultrarapidly frozen embryos of the marine brown algaPelvetia fastigiata has demonstrated the presence of numerous 0.5-MUm diameter, disc shaped vesicles lying adjacent and nearly parallel to the plasma membrane. Some vesicles are fused with the plasma membrane through a narrow connection; this however appears to be a reversible attachment rather than an intermediate stage in the incorporation of the vesicle into the plasma membrane. The distribution of these connections in the plane of the membrane is not uniform; they tend to occur in patches. The fraction of vesicles that is fused with the plasma membrane at any one time appears to be related to a cell's perception of a stressful hypotonic imbalance between the internal and external concentrations of osmotically active compounds. Thus, a sudden 5% decrease in osmolarity of the artificial seawater medium just before freezing leads to a 38% increase in connections per unit membrane area, while a 20% decrease in osmolarity leads to a 75% increase in connections per unit area. Based on these findings and the corresponding ion-transport studies of R. Nuccitelli and L.F. Jaffe (1976, Planta131, 315-320), we postulate that the disc-shaped vesicles mediate short term osmoregulation inPelvetia embryos by reversibly inserting chloride channels into the plasma membrane. PMID- 24213039 TI - Partial purification and initial characterization of phytochrome from the mossAtrichum undulatum P. Beauv. grown in the light. AB - The extraction and partial purification of phytochrome from light-grownAtrichum undulatum P. Beauv., a chlorophyllous moss, is described. Polyethyleneimine and salt fractionation followed by hydroxyapatite and Affi-gel-blue chromatography were used to separate phytochrome from chlorophyll, and to purify the pigment. All steps were performed in the presence of Triton X-100 which improved the yield by a factor of about three. The protein has a molecular weight some-what larger than that ofAvena phytochrome (124 kDa), as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblot analysis. It cross-reacts with a monoclonal antibody against phytochrome from etiolated corn (Zea) and a polyclonal antibody against phytochrome from etiolated oat (Avena), and its photoreversibility is similar to that of phytochrome from greenAvena. PMID- 24213040 TI - Measurement of internal pH in the coccolithophoreEmiliania huxleyi using 2',7' bis-(2-carboxyethyl)-5(and-6)carboxyfluorescein acetoxymethylester and digital imaging microscopy. AB - Internal pH (pHi) was determined inEmiliania huxleyi (Lohmann) using the probe 2',7'-bis-(2-carboxyethyl)-5(and-6)carboxyfluoresceinacetoxymethylester (BCEF-AM) and digital imaging microscopy. The probe BCECF-AM was taken up and hydrolysed to the free acid by the cells. A linear relationship was established between pHi and the 490/450 fluorescence ratio of BCECF-AM over the pH range 6.0 to 8.0 using the ionophore nigericin. Two distinct pH domains were identified within the cell, the cytoplasmic domain (approx. pH 7.0) and the chloroplast domain (approx. pH 8.0). The average pHi was 7.29 (+/-0.11) for cells in the presence of 2 mM HCO 3 (-) . In the absence of HCO 3 (-) the pHi was decreased by 0.8 pH unit. The importance of these changes in pHi is considered in relation to inorganic-carbon uptake. PMID- 24213041 TI - Inorganic-carbon transport in some marine eukaryotic microalgae. AB - Inorganic-carbon transport was investigated in the eukaryotic marine microalgaeStichococcus minor, Nannochloropsis oculata and aMonallantus sp. Photosynthetic O2 evolution at constant inorganic-carbon concentration but varying pH showed thatS. minor had a greater capacity for CO2 rather than HCO 3 ( ) utilization but forN. oculata andMonallantus HCO 3 (-) was the preferred source of inorganic carbon. All three microalgae had a low affinity for CO2 as shown by the measurement of inorganic-carbon-dependent photosynthetic O2 evolution at pH 5.0. At pH 8.3, where HCO 3 (-) is the predominant form of inorganic carbon, the concentration of inorganic carbon required for half-maximal rate of photosynthetic O2 evolution [K 0.5 (CO2)] was 53 MUM forMonallantus sp. and 125 MUM forN. oculata, values compatible with HCO 3 (-) transport. Neither extra- nor intracellular carbonic anhydrase was detected in these three microalgal species. It is concluded that these microalgae lack a specific transport system for CO2 but that HCO 3 (-) transport occurs inN. oculata andMonallantus, and in the absence of intracellular carbonic anhydrase the conversion of HCO 3 (-) to CO2 may be facilitated by the internal pH of the cell. PMID- 24213042 TI - Effects of light and acetate on the liberation of zoospores by a mutant strain ofChlamydomonas reinhardtii. AB - In light-dark-synchronized cultures of the unicellular green algaChlamydomonas reinhardtii, release of zoospores from the wall of the mother cell normally takes place during the second half of the dark period. The recently isolated mutant 'ls', however, needs light for the liberation of zoospores when grown photoautotrophically under a 12 h light-12 h dark regime. The light-induced release of zoospores was found to be prevented by addition of the photosystem-II inhibitor 3-(3',4'-dichlorophenyl)-1,1-dimethylurea. Furthermore, light dependence of this process was shown to be abolished when the mutant 'ls' was grown either photoautotrophically under a 14 h light-10 h dark regime or in the presence of acetate. Our findings indicate that the light-dependency of zoospore liberation observed in cultures of this particular mutant during photoautotrophic growth under a 12 h light-12 h dark regime might be attributed to an altered energy metabolism. The light-induced release of zoospores was found to be prevented by addition of cycloheximide or chloramphenicol, antibiotics which inhibit protein biosynthesis by cytoplasmic and organellar ribosomes, respectively. Actinomycin D, an inhibitor of RNA synthesis, however, did not affect the light-induced liberation of zoospores.Sporangia accumulate in stationary cultures of the mutant 'ls'. Release of zoospores was observed when these sporangia were collected by centrifugation and incubated in the light after resuspension in fresh culture medium. Since liberation of zoospores was not observed after dilution of the stationary cultures with fresh culture medium, we suppose that components which interfere with the action of the sporangial autolysin are accumulated in the culture medium of the mutant 'ls'. PMID- 24213043 TI - A model of photosynthetic CO2 assimilation and carbon-isotope discrimination in leaves of certain C3-C 4 intermediates. AB - A model of leaf, photosynthesis has been developed for C3-C4 intermediate species found in the generaPanicum, Moricandia, Parthenium andMollugo where no functional C4 pathway has been identified. Model assumptions are a functional C3 cycle in both mesophyll and bundle-sheath cells and that glycine formed in the mesophyll, as a consequence of the oxygenase activity of ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco, EC 4.1.1.39), diffuses to the bundle sheath, where most of the photorespiratory CO2 is released. The model describes the observed gas-exchange characteristics of these C3-C4 intermediates, such as low CO2-compensation points (Gamma) at an O2 pressure of 200 mbar, a curvilinear response of Gamma to changing O2 pressures, and typical responses of CO2 assimilation rate to intercellular CO2 pressure. The model predicts that bundle sheath CO2 concentration is highest at low mesophyll CO2 pressures and decreases as mesophyll CO2 pressure increases. A partitioning of 5-15% of the total leaf Rubisco into the bundle-sheath cells and a bundlesheath conductance similar to that proposed for C4 species best mimics the gas-exchange results. The model predicts C3-like carbon-isotope discrimination for photosynthesis at atmospheric levels of CO2, but at low CO2 pressures it predicts a higher discrimination than is typically found during C3 photosynthesis at lower CO2 pressures. PMID- 24213044 TI - Short-term carbon-isotope discrimination in C3-C 4 intermediate species. AB - Short-term discrimination in assimilation of stable isotopes of carbon was measured for leaves of the C3 speciesPhaseolus vulgaris L. cv. Hawkesbury Wonder andFlaveria pringlei Gandoger, the C4 speciesAmaranthus edulis Speg., and the C3 C4 intermediate speciesPanicum milioides Nees ex. Trin,Flaveria floridana Johnson, andFlaveria anomala B.L. Robinson. Discriminations in the C3 and C4 species were similar to those expected from theoretical considerations. When ambient CO2 pressure was 330 MUbar the mean discriminations in the C3 species andPanicum milioides were similar, whereas the mean discriminations inF. floridana andF. anomala were less than discrimination in C3 species andPanicum milioides. When ambient CO2 pressure was 100 MUbar the mean discriminations inPanicum milioides andF. anomala were greater, and that inF. floridana was less, than that inPhaseolus vulgaris. We conclude that the pattern of discrimination inPanicum milioides is consistent with the presence of a glycine shuttle; inF. floridana andF. anomala, discrimination is consistent with the presence of a C4 pathway coupled with the operation of a glycine shuttle. PMID- 24213045 TI - Correlation of spermine levels with ovary senescence and with fruit set and development inPisum sativum L. AB - Separation and quantitation of polyamines from unpollinated pea (Pisum sativum L.) ovaries and young fruits induced by application of gibberellic acid to unpollinated ovaries showed, in both cases, a decrease in putrescine and spermidine levels between anthesis and 4 d later. By contrast, spermine levels increased prior to the onset of senescence of the unpollinated ovaries (3 d post anthesis) and decreased during fruit development. Low levels of putrescine, spermidine and spermine were also observed in young fruits obtained by self pollination and by treatment of unpollinated ovaries with 2,4 dichlorophenoxyacetic acid. In-vitro culture of ovary explants in a medium containing spermine showed that a reduction of the growth of gibberellic acid treated unpollinated ovaries was associated with a rise in the level of spermine in the fruits. The results obtained indicate that changes in spermine levels are involved in the control of ovary senescence and of fruit set and development. PMID- 24213046 TI - Radial transport of water across cortical sleeves of excised roots ofZea mays L. AB - The stationary radial volume flows across maize (Zea mays L.) root segments without steles ("sleeves") were measured under isobaric conditions. The driving force of the volume flow is an osmotic difference between the internal and external compartment of the root preparations. It is generated by differences in the concentrations of sucrose, raffinose or polyethylene glycol. The flows are linear functions of the corresponding osmotic differences (Delta pi) up to osmotic values which cause plasmolysis. The straight lines obtained pass through the origin. No asymmetry of the osmotic barrier could be detected within the range of driving forces applied (delta pi=+/-0.5 MPa), corresponding to volume flow densities of jv, s=+/-7.10(-8) m.s(-1). Using the literature values for the reflection coefficients of sucrose and polyethylene glycol in intact roots (E. Steudle et al. (1987) Plant Physiol.84, 1220-1234), values for the sleeve hydraulic conductivity of about 1.10(-7) m.s(-1) MPa(-1) were calculated. They are of the same order of magnitude as those reported in the literature for the hydraulic conductivity of intact root segments when hydrostatic pressure is applied. PMID- 24213047 TI - Mechanisms of fusicoccin action: evidence for concerted modulations of secondary K(+) transport in a higher plant cell. AB - Fusicoccin (FC) has long been known to promote K(+) uptake in higher plant cells, including stomatal guard cells, yet the precise mechanism behind this enhancement remains uncertain. Membrane hyperpolarization, thought to arise from primary H(+) pumping stimulated in FC, could help drive K(+) uptake, but the extent to which FC stimulates influx and uptake frequently exceeds any reasonable estimates from Constant Field Theory based on changes in the free-running membrane potential (V m) alone; furthermore, unidirectional flux analyses have shown that in the toxin K(+) ((86)Rb(+)) exchange plummets to 10% of the control (G.M. Clint and E.A.C. MacRobbie 1984, J. Exp. Bot.35 180-192). Thus, the activities of specific pathways for K(+) movement across the membrane could be modified in FC. We have explored a role for K(+) channels in mediating these fluxes in guard cells ofVicia faba L. The correspondence between FC-induced changes in chemical ((86)Rb(+)) flux and in electrical current under voltage clamp was followed, using the K(+) channel blocker tetraethylammonium chloride (TEA) to probe tracer and charge movement through K(+)-selective channels. Parallel flux and electrical measurements were carried out when cells showed little evidence of primary pump activity, thus simplifying analyses. Under these conditions, outward-directed K(+) channel current contributed appreciably to charge balance maintainingV m, and adding 10 mM TEA to block the current depolarized (positive-going)V m; TEA also reduced(86)Rb(+) efflux by 68-80%. Following treatments with 10 MUM FC, both K(+) channel current and(86)Rb(+) efflux decayed, irreversbly and without apparent lag, to 10%-15% of the controls and with equivalent half-times (approx. 4 min). Fusicoccin also enhanced(86)Rb(+) influx by 13.9-fold, but the influx proved largely insensitive to TEA. Overall, FC promotednet cation uptake in 0.1 mM K(+) (Rb(+)), despite membrane potentials which were 30-60 mVpositive of the K(+) equilibrium potential. These results tentatively link (chemical) cation efflux to charge movement through the K(+) channels. They offer evidence of an energy-coupled mechanism for K(+) uptake in guard cells. Finally, the data reaffirm early suspicions that FC alters profoundly the K(+) transport capacity of the cells, independent of any changes in membrane potential. PMID- 24213048 TI - Mechanisms of fusicoccin action: kinetic modification and inactivation of K(+) channels in guard cells. AB - Fusicoccin commonly is thought to promote secondary solute transport via an increase in electrical driving force which follows the enhancement of primary, "electrogenic" H(+) extrusion by the plant plasma membrane H(+)-ATPase. However, previous electrical studies ofVicia faba L. guard cells in FC (Blatt, 1988, Planta174, 187) demonstrated, in addition to a limited rise in pump current, appreciable declines in membrane conductance near and positive to the free running membrane potential (V m). Much of the current at these potentials could have been carried by outward-rectifying K(+) channels which were progressively inactivated in FC. We have examined this possibility in electrical studies, using whole-cell currents measured under voltage clamp to quantitate steadystate and kinetic characteristics of the K(+) channels both before and during exposure to FC; channels block in tetraethylammonium chloride was exploited to assess changes in background 'leak' currents. The cells showed little evidence of primary pump activity, a fact which further simplified analyses. Under these conditions, outward-directed K(+) channel current contributed to charge balance maintainingV m, and adding 10 MUM FC on average depolarized (positive-going)V m. Steady-state current-voltage relations revealed changes both in K(+) channel and in leak currents underlying the voltage response. Changes in the leak were variable, but on average the leak equilibrium potential was shifted (+)19 mV and leak conductance declined by 21% over 30-40 min in FC. Potassium currents were inactivated irreversibly and with halftimes (current maxima) of 6.2-10.7 min. Inactivation was voltage-dependent, so that the activation ("gating") potential for the current was shifted, positive-going, with time in FC. Channel gating kinetics, inferred from the macroscopic currents, were also affected; current rise at positive potentials accelerated 4.5-fold and more, but in a manner apparently independent of voltage and extracellular potassium concentration. Current decay at negative potentials was quickened, also. These results identify the outward-rectifying K(+) channels as one site of action for FC at a higher plant cell membrane; they complete the link introduced in the preceding paper between K(+) channel current, K(+)((86)Rb(+)) flux and irreversible cation uptake in the toxin. The data also offer some insights toward a kinetic description of channel gating. Finally, they provide a vehicle for interpreting FC-induced changes in K(+) and net H(+) flux, and in membrane potential without the necessity for postulating gross changes in H(+) pumping. PMID- 24213049 TI - Nuclear-magnetic-resonance imaging of leaves ofMesembryanthemum crystallinum L. plants grown at high salinity. AB - Differences in water binding were measured in the leaf cells ofMesembryanthemum crystallinum L. plants grown under high-salinity conditions by using nuclear magnetic-resonance (NMR) imaging. The 7-Tesla proton NMR imaging system yielded a spatial resolution of 20.20.100 MUm(3). Images recorded with different spin-echo times (4.4 ms to 18 ms) showed that the water concentrations in the bladder cells (located on the upper and lower leaf surface), in the mesophyll cells and in the water-conducting vessels were nearly identical. All of the water in the bladder cells and in the water-conducting vessels was found to be mobile, whilst part of the water in the mesophyll cells was bound. Patches of mesophyll cells could be identified which bound water more strongly than the surrounding mesophyll cells. Optical investigations of leaf cross-sections revealed two types of mesophyll cells of different sizes and chloroplast contents. It is therefore likely that in the small-sized mesophyll cells water is strongly bound. A long-term asymmetric water exchange between the mesophyll cells and the bladder cells during Crassulacean acid metabolism has been described in the literature. The high density of these mesophyll cells in the lower epidermis is a possible cause of this asymmetry. PMID- 24213050 TI - Organization of the actin cytoskeleton during pollen development inGasteria verrucosa (Mill.) H. Duval visualized with rhodamine-phalloidin. AB - The three-dimensional organization of the microfilamental cytoskeleton of developingGasteria pollen was investigated by light microscopy using whole cells and fluorescently labelled phalloidin. Cells were not fixed chemically but their walls were permeabilized with dimethylsulphoxide and Nonidet P-40 at premicrospore stages or with dimethylsulphoxide, Nonidet P-40 and 4 methylmorpholinoxide-monohydrate at free-microspore and pollen stages to dissolve the intine.Four strikingly different microfilamentous configurations were distinguished. (i) Actin filaments were observed in the central cytoplasm throughout the successive stages of pollen development. The network was commonly composed of thin bundles ramifying throughout the cytoplasm at interphase stages but as thick bundles encaging the nucleus prior to the first and second meiotic division. (ii) In released microspores and pollen, F-actin filaments formed remarkably parallel arrays in the peripheral cytoplasm. (iii) In the first and second meiotic spindles there was an apparent localization of massive arrays of phalloidin-reactive material. Fluorescently labelled F-actin was present in kinetochore fibers and pole-to-pole fibers during metaphase and anaphase. (iv) At telophase, microfilaments radiated from the nuclear envelopes and after karyokinesis in the second meiotic division, F-actin was observed in phragmoplasts.We did not observe rhodamine-phalloidin-labelled filaments in the cytoplasm after cytochalasin-B treatment whereas F-actin persisted in the spindle. Incubation at 4 degrees C did not influence the existence of cytoplasmic microfilaments whereas spindle filaments disappeared. This points to a close interdependence of spindle microfilaments and spindle tubules.Based on present data and earlier observations on the configuration of microtubules during pollen development in the same species (Van Lammeren et al., 1985, Planta165, 1 11) there appear to be apparent codistributions of F-actin and microtubules during various stages of male meiosis inGasteria verrucosa. PMID- 24213051 TI - Revision of the theory of phototropism in plants: a new interpretation of a classical experiment. AB - Went's classical experiment on the diffusion of auxin activity from unilaterally illuminated oat coleoptile tips (Went 1928), was repeated as precisely as possible. In agreement with Went's data with theAvena curvature assay, the agar blocks from the illuminated side of oat (Avena sativa L. cv. Victory) coleoptile tips had, on an average, 38% of the auxin activity of those from the shaded side. However, determination of the absolute amounts of indole-3-acetic acid (IAA) in the agar blocks, using a physicochemical assay following purification, showed that the IAA was evenly distributed in the blocks from the illuminated and shaded sides. In the blocks from the shaded and dark-control halves the amounts of IAA were 2.5 times higher than the auxin activity measured by theAvena curvature test, and in those from the illuminated half even 7 times higher. Chromatography of the diffusates prior to theAvena curvature test demonstrated that the amounts of two growth inhibitors, especially of the more polar one, were significantly higher in the agar blocks from the illuminated side than in those from the shaded side and the dark control. These results show that the basic experiment from which the Cholodny-Went theory was derived, does not justify this theory. The data rather indicate that phototropism is caused by the light-induced, local accumulation of growth inhibitors against a background of even auxin distribution, the diffusion of auxin being unaffected. PMID- 24213052 TI - Inhibition of photosynthesis by chilling in moderate light: a comparison of plants sensitive and insensitive to chilling. AB - Photosynthetic activity, in leaf slices and isolated thylakoids, was examined at 25 degrees C after preincubation of the slices at either 25 degrees C or 4 degrees C at a moderate photon flux density (PFD) of 450 MUmol.m(-2).s(-1), or at 4 degrees C in the dark. The plants used wereSpinacia oleracea L.,Cucumis sativus L. andNerium oleander L. which was acclimated to growth at 20 degrees C or 45 degrees C. The plants were grown at a PFD of 550 MUmol.m(-2).s(-1). Photosynthesis, measured as CO2-dependent O2 evolution, was not inhibited in leaf slices from any plant after preincubation at 25 degrees C at a moderate PFD or at 4 degrees C in the dark. However, exposure to 4 degrees C at a moderate PFD induced an inhibition of CO2-dependent O2 evolution within 1 h inC. sativus, a chilling-sensitive plant, and in 45 degrees C-grownN. oleander. The inhibition in these plants after 5 h reached 80% and 40%, respectively, and was independent of the CO2 concentration but was reduced at O2 concentrations of less than 3%. Methyl-viologen-dependent O2 exchange in leaf slices from these plants was not inhibited. There was no photoxidation of chlorophyll, in isolated thylakoids, or any inhibition of electron transport at photosystem (PS)II, PSI or through both photosystems which would account for the inhibition of photosynthesis. The conditions which inhibit photosynthesis in chilling-sensitive plants do not cause inhibition inS. oleracea, a chilling-insensitive plant, or in 20 degrees C grownN. oleander. The CO2-dependent photosynthesis, measured at 5 degrees C, was reduced to about 3% of that recorded at 25 degrees C in chilling-sensitive plants but only to about 30% in the chilling-insensitive plants. Methyl-viologen dependent O2 exchange, measured at 5 degrees C, was greater than 25% of the activity at 25 degrees C in all the plants. The results indicate that the mechanism of the chilling-induced inhibition of photosynthesis does not involve damage to PSII. That inhibition of photosynthesis is observed only in the chilling-sensitive plants indicates it is related, in some way, to the disproportionate decrease in photosynthetic activity in these plants at chilling temperatures. PMID- 24213053 TI - Relationship between the octanol-water partition coefficient of tertiary amines and their effect of 'selective' uncoupling of photophosphorylation. AB - A series of tertiary amines was investigated for effects on the transmembrane proton potential difference (Delta [Formula: see text]H), on photophosphorylation and on electron-flux control related to the intrathylakoid proton potential ([Formula: see text]HI), using isolated chloroplasts ofSpinacia oleracea L. As indicated by 9-aminoacridine fluorescence and [14C]methylamine uptake, all amines studied inhibited a build-up ofDelta [Formula: see text]H and, in parallel, ATP synthesis. Even whenDelta [Formula: see text]H was low, strong[Formula: see text]H1-dependent electron-flux control was observed under the influence of tertiary amines. The strength of flux control in the presence of lowDelta [Formula: see text]H and the effectiveness of inhibition of ATP synthesis linearly increased with the lipophilicity of the amines. The most effective of the amines tested caused 50% inhibition of ATP synthesis at a concentration of 6 MUM, which is about 1000-fold lower than the concentration required for inhibition by methylamine. The data presented indicate the existence of two proton domains in the thylakoid vesicles, one of them feeding the ATP-synthase, the other the sites of pH-dependent electron-flux control. It is concluded that tertiary amines develop their action in a lipophilic domain of the thylakoid membrane, in the vicinity of the ATP-synthase complex. A mechanism for 'selective' uncoupling and for the maintenance of[Formula: see text]HI-dependent electron flux control in the presence of lowDelta [Formula: see text]H is discussed. PMID- 24213055 TI - Genetic and molecular analysis of tissue-culture-derived Ac elements. AB - Our previous experiments on maize (Zea mays L.) plants regenerated from tissue culture revealed genetic activity characteristic of the transposable element Activator (Ac) in the progeny of 2-3% of the plants tested, despite the lack of Ac activity in the progenitor plants. The objective of the present study was to determine whether the presence of Ac activity in tissue-culture-derived plants was associated with changes in the number or structure of Ac-homologous DNA sequences. Families segregating for Ac activity were obtained by crossing plants heterozygous for Ac activity onto Ac-responsive tester plants. A DNA probe derived from a previously isolated Ac sequence was used to examine the Ac homologous sequences within individual progeny seedlings of segregating families and noncultured control materials. All plants tested had six or more Ac homologous DNA sequences, regardless of whether Ac activity was present. In the segregating progeny of one tissue-culturederived plant, a 30-kb Ac-homologous SstI restriction fragment and a 10-kb Ac-homologous BglII restriction fragment were found to cosegregate with Ac activity. We propose that these fragments contained a previously silent Ac sequence that had been activated during tissue culture. Although one or more Ac sequences were often hypomethylated at internal PvuII and HpaII sites in plants with Ac activity, hypomethylation was not a prerequisite for activity. Reduced methylation at these sites may have been a result rather than a cause of Ac activity. PMID- 24213056 TI - Evaluation of parents and selection for heat tolerance in the early generations of a potato (Solanum tuberosum L.) breeding program. AB - Potato cultivars (Solanum tuberosum L.) were evaluated for their capacity to form tubers under high temperature conditions (heat tolerance). In an experiment conducted in the hot summer season in the field and in experiments conducted under controlled environments in glasshouses, differences in tolerance to heat were noted among the various genotypes. Although heat tolerance tended to be associated with earliness in maturation, differences in the response to high temperatures were observed in genotypes of the same maturity class. Progeny of the cultivars Desiree and Cara, and hybrid progeny of Cara x Desiree and of Blanka x Cara were screened for heat tolerance in controlled environments in glasshouses. Long photoperiod delayed tuberization but high temperatures strongly inhibited tuber formation, which was 4% in the progeny of Desiree, <2% in the progeny of Cara and of Cara x Desiree, and ca. 16% in progeny of Blanka x Cara. For seedlings that did not form tubers in the hot glasshouse but were subsequently transferred to the cool glasshouse, tuberization was much enhanced and clones selected through this dual procedure exhibited tolerance to heat in the first conal year. The results of this study indicate that: (a) tolerance to heat is associated with earliness; however, differences in the response to heat exist among late-maturing cultivars; (b) tolerance to heat, as assessed by the capacity to form tubers under high temperatures, is genetically controlled, and the timing of tuberization might be independent of the rate of tuberization in hybrid progeny; (c) the incidence of heat tolerance in progeny population is correlated with the relative tolerance of the parents; and (d) the dual selection procedure is an efficient approach for the selection of heat-tolerant clones. PMID- 24213057 TI - Complex determination of male sterility in Thymus vulgaris L.: genetic and molecular analysis. AB - Nucleocytoplasmic determination of male sterility in Thymus vulgaris L. has been assumed in all papers attempting to explain the remarkably high frequencies of male steriles found in natural populations of this species. This paper provides strong evidence that both nuclear and cytoplasmic genes are involved in the determination of male sterility of this species, giving a complex inheritance. Interpopulation and intrapopulation crosses have shown that the ratio of females versus hermaphrodites among offsprings varied widely from 1?0 to 1?1. Furthermore, interpopulation crosses consistently yielded a higher frequency of females than intrapopulation crosses. Nucleocytoplasmic inheritance was demonstrated by an absence of male fertiles in backcrosses and asymmetrical segregation in reciprocal crosses. Molecular analysis of the mitochondrial DNA of some of the parents used in crosses suggested the involvement of different cytoplasms in the inheritance of male steriliy. PMID- 24213058 TI - Sex determination in the genus Oreochromis : 1. Sex reversal, gynogenesis and triploidy in O. niloticus (L.). AB - Established techniques of genetic manipulation were used to elucidate sex determining mechanisms in the commercially important tilapia, Oreochromis niloticus. Analysis of sex ratios from single-pair matings of normal broodstock showed these to be heterogeneous, with an asymmetrical frequency distribution. Data were homogeneous, with the exclusion of a number of broods with sex ratios not significantly different from 3?1 (male: female), and further progeny testing revealed atypical female heterogamety in the parents of these broods. Analysis of sex ratios from complete diallele-type crosses using five males and five females demonstrated no association between male parent, female parent and progeny sex ratio. Sex ratios of gynogens (0?1) and triploids (1?1), and from progeny testing of sex-reversed males (0?1) and sex-reversed females (3?1), provide evidence for female homogamety in this species. Progeny testing of male gynogens derived from sex-reversed females demonstrated recombination between the centromere and the sex-determining locus (68.9%). Novel YY "supermales" were shown to be viable and produced all-male offspring. It was concluded that this species exhibits monofactorial, genotypic sex determination with male heterogamety. However, rare autosomal or environmental sex-modifying factors may account for occasional deviations from expected sex ratios. PMID- 24213059 TI - Sex determination in the genus Oreochromis : 2. Sex reversal, hybridisation, gynogenesis and triploidy in O. aureus Steindachner. AB - Sex ratios from 62 single-pair matings of normal broodstock O. aureus were highly heterogeneous with an overall deficit of males (41.4%). Peaks in the sex ratio frequency distribution occurred at 1?1, 3?5 and 1?3 (male?female). Hybridisation of O. aureus with O. mossambicus, O. spilums and O. niloticus produced highly variable sex ratios, suggesting a complexity of hybrid sex determination. Few valid inferences could be made regarding intraspecific sex determination from these hybrid data. Sex ratios from progeny testing of sex-reversed males (1?3) and most sex-reversed females (1?0) provide evidence for female heterogamety in O. aureus. Several aberrant ratios observed suggest Mendelian inheritance of an autosomal recessive gene (F,f), epistatic to the major sex-determining gene (W,Z). Sex ratios of triploids and gynogens support the hypothesis of recombination between the centromere and the major sex-determining locus. Progeny testing of a female mitogyne demonstrated the viability of a novel WW "superfemale", which gave only female offspring. Not all data could be explained by a two-factor model of sex determination. Further exceptional sex ratios may be accounted for by rare autosomal or environmental sex-modifying factors. It is concluded that O. aureus has a multifactorial mechanism of sex determination with the underlying primary mechanism of female heterogamety. PMID- 24213060 TI - Stable transformation of Sorghum bicolor protoplasts with chimeric neomycin phosphotransferase II and beta-glucuronidase genes. AB - Parameters influencing the stable transformation of Sorghum bicolor protoplasts with a chimeric neomycin phosphotransferase II (NPT II) gene by electroporation were investigated. The mean number of kanamycin-resistant calli produced increased in direct proportion to the concentration of DNA used for transformation. Linearization of the plasmid doubled the mean number of kanamycin resistant calli produced, while the addition of carrier DNA had no effect. The copy number (1-4) of integrated genes was low compared with that frequently reported for PEG-mediated transformation. Two strategies for transforming protoplasts with a nonselectable, beta-glucuronidase (GUS) gene were compared. One utilized a plasmid containing a CaMV 35S-NPT II gene covalently linked to a CaMV 35S-GUS gene, and the other strategy utilized the two genes on separate plasmids. DNA from all 77 kanamycin-resistant calli analyzed contained restriction fragments hybridizing to the NPT II probe; approximately 70% of the clones from all transformation treatments contained a 1.7-kb EcoRI/HindIII restriction fragment corresponding to the full-length gene. Of the kanamycin resistant calli, 38-63% (depending on the transformation treatment) contained GUS hybridizing fragments, and 8-19% contained the full-length gene. The addition of NPT II and GUS genes on a single plasmid or on separate plasmids did not appear to lead to an appreciable difference in the frequency of cointegration of these genes, although an increased proportion of the plasmid bearing the nonselectable (GUS) gene appeared to favor its cointegration. PMID- 24213061 TI - Gene flow in an almond orchard. AB - Gene flow by pollen between trees is essential for nut set in commercial almond orchards, due to the self-incompatibility of almond cultivars used. A study of gene flow has been carried out in an orchard composed of single rows of a "pollinating" cultivar between every double row of the most commercially desirable cultivar, Nonpareil. This "two-to-one" planting pattern was repeated throughout the orchard, and several "pollinating" cultivars were used in various parts of the orchard in an attempt to provide flowers for cross-pollination with Nonpareil at all stages of flowering of the latter. Using isozyme markers GPI-2, LAP-1, AAT-1, PGM-1, and PGM-2 and three newly-defined isozyme markers for almond - IDH, G6PD, and SDH - it has been shown that the gene flow resulting in nut set is quite restricted, taking place most strongly between neighboring halves of cross-compatibile pairs of trees. Even that half of a tree facing away from the "pollinating" tree has significantly less gene flow to it, while the next tree further on has few nuts set by fertilization from the "pollinating" tree under consideration. This result is surprising considering the comparatively large distances that the honeybee brought into the orchard in large numbers must travel within the orchard. To explain this apparent paradox and the observation that in most cases only a small proportion (<20%) of flowers set nuts, it is suggested that the honeybee predominantly visits only one cultivar, flying along the row of the cultivar to do so, and that cross-pollination results from accidental or rare visits involving two or more compatible cultivars. PMID- 24213062 TI - RFLP-based genetic map of rye (Secale cereale L.) chromosome 1R. AB - A map of chromosome 1R of rye was constructed using 16 molecular and biochemical loci. From long arm to short arm, known-function loci were placed in the order: XAdh - XLee - Glu-R1[Sec-3] - XPpdk-1R - XEm-1R-1 - XEm-1R-2 - Centromere - XNor R1 -Gpi-R1 - XGli-R1 [Sec-1a] along with six anonymous genomic and cDNA clones from wheat. The map, which spans 106 cM with 12 loci clustered in a 15-cM region around the centromere, shows reasonably good agreement with previously published maps for the centromeric region, whereas the XNor-R1 - Gpi-R1 region gives a much larger distance than previously reported. PMID- 24213063 TI - RFLP analysis of nuclear DNAs homologous with mitochondrial plasmid-like DNAs in cultivated rice. AB - B1 and B2 are small, circular, mitochondrial plasmid-like DNAs found in male sterile cytoplasm (cms-Bo) of rice. In this study, nuclear sequences homologous to these DNAs were investigated among a number of rice cultivars. Several copies of nuclear B1-and B2-homologous sequences were detected in all examined cultivars, regardless of the presence or absence of the B1 and B2 DNAs in mitochondria, indicating that the existence of the B1- and B2-homologous sequences in the rice nuclear genome was widespread. A restriction fragment length polymorphism (RFLP) was detected for both sequences, and we propose that these DNAs could be useful RFLP markers for the rice nuclear genome. To analyze these nuclear homologues genetically, segregation analysis of the RFLP was carried out in the F2 progenies of an Indica-Japonica rice hybrid. Of the B1 homologues, there were two nonallelic fragments, one specific to the Indica parent and the other to the Japonica. These results indicate that the B1 and B2 homologues were dispersed in the nuclear genome. The integration of B1-homologous DNA into the nuclear DNA may have occurred independently after sexual isolation of the Indica and Japonica rice varietal groups, or a intranuclear transposition of these sequences took place during the process of rice differentiation into the varietal groups. PMID- 24213064 TI - Genetic variation in somatic embryogenic response in open-pollinated families of black spruce. AB - Zygotic embryos from open-pollinated seeds of 20 black spruce (Picea mariana) families were used to investigate the proportion of genotypes that would give rise to embryogenic tissue (ET) and mature somatic embryos. Eighty-five percent of the maternal genotypes gave rise to embryogenic tissue. Within-family rates of ET induction ranged from 0 to 17%, with an average of 8%. The largest proportion of variation was among families, indicating the additive nature of the genetic variation. On a medium with 6% sucrose and 3.7 MUM ABA, 90% of the embryogenic lines gave rise to abundant (>100/100 mg of ET), well-formed, mature somatic embryos. A medium with 2% sucrose, without 2,4-D, was used to germinate the mature somatic embryos. These were grown in the greenhouse and have now been established in field trials. PMID- 24213065 TI - Plant cells selected for resistance to phosphate starvation show enhanced P use efficiency. AB - In many organisms, phosphate starvation induces multigene systems that act to increase the availability and uptake of exogenous phosphates. Tissue-cultured tomato cells were plated onto solid media containing starvation levels of phosphate. While most cells died, we identified isolated clumps of callus capable of near-normal rates of growth. Starvation-resistant cells were used to start suspension cultures that were kept under phosphate starvation conditions. A selected cell line showed constitutively enhanced secretion of acid phosphatase and greatly increased rates of phosphate uptake. These pleiotropic effects suggest modification of a regulatory apparatus that controls coordinated changes in the expression of a multigene system. The somaclonal variant cell line grew normally under phosphate-sufficient conditions, but did significantly better than unselected cells under phosphate-limited conditions. In vitro selection may be a useful system for developing phosphate ultraefficient crop plants. PMID- 24213066 TI - Isozyme and plastid DNA assessment of pedigrees of nineteenth century potato cultivars. AB - Isozyme and ctDNA RFLP patterns were determined for ten historically important potato cultivars (Solanum tuberosum ssp. tuberosuni) in order to relate and confirm their pedigrees. Isozyme polymorphism was detected at 11 of 13 loci examined, whereas only T-type cytoplasm, the predominant ctDNA of S. tuberosum ssp. tuberosum, was observed. Isozyme analysis indicated that potato cultivars previously presumed to be derived from open-pollinated berries of Garnet Chili and Early Rose were in fact the result of hybridizations. In addition, putative pedigrees of Irish Cobbler, White Rose, and Bliss Triumph were not supported. Garnet Chili, the first derivative of Rough Purple Chili, carries allozmyes at Mdh-1 and Pgm-2, which supports the Chilean origin of Rough Purple Chili. The identical ctDNA pattern among the cultivars may indicate a common maternal lineage that traces through Garnet Chili to Rough Purple Chili. The allozyme frequencies estimated from these cultivars provide a base from which subsequent introductions of Solanum species into the ssp. tuberosum gene pool can be assessed. PMID- 24213067 TI - Variability and uniformity of mitochondrial DNA in populations of putative diploid ancestors of common wheat. AB - By using restriction endonuclease digestion patterns, the degree of intraspecific polymorphism of mitochondrial DNA in four diploid species of wheat and Aegilops, Ae. speltoides, Ae. longissima, Ae. squarrosa, and Triticum monococcum, was assessed. The outbreeding Ae. speltoides was found to possess the highest degree of variability, the mean number of nucleotide substitutions among conspecific individuals being 0.027 substitutions per nucleotide site. A very low degree of mtDNA variation was detected among Ae. longissima accessions, with most of the enzyme-probe combinations exhibiting uniform hybridization patterns. The mean number of substitutions among Ae. longissima individuals was 0.001 substitutions per nucleotide site. The domesticated diploid wheat T. monococcum var. monococcum and its conspecific variant T. monococcum var. boeoticum seem to lack mitochondrial DNA variability altogether. Thus, the restriction fragment pattern can be used as a characteristic identifier of the T. monococcum cytoplasmic genome. Similarly, Ae. squarrosa accessions were found to be genetically uniform. A higher degree of variation among accessions is observed when noncoding sequences are used as probes then when adjacent coding regions are used. Thus, while noncoding regions may contain regulatory functions, they are subject to less stringent functional constraints than protein-coding regions. Intraspecific variation in mitochondrial DNA correlates perfectly with the nuclear variability detected by using protein electrophoretic characters. This correlation indicates that both types of variation are selectively neutral and are affected only by the effective population size. PMID- 24213068 TI - Identification and mapping of polymorphisms in cereals based on the polymerase chain reaction. AB - The polymerase chain reaction (PCR) can be used to detect polymorphisms in the length of amplified sequences between the annealing sites of two synthetic DNA primers. When the distance varies between two individuals then the banding pattern generated by the PCR reaction is essentially a genetic polymorphism and can be mapped in the same way as other genetic markers. This procedure has been used in a number of eukaryotes. Here we report the use of PCR to detect genetic polymorphisms in cereals. Known gene sequences can be used to design primers and detect polymorphic PCR products. This is demonstrated with primers to the alpha amylase gene family. A second approach is to use semi-random primers to target diverse regions of the genome. For this purpose the consensus sequences at the intron-exon splice junctions were used. The targeting of the intronexon splice junctions in conjunction with primers of random and defined sequences, such as alpha-amylase, provides a source of extensive variation in PCR products. These polymorphisms can be mapped as standard genetic markers. PMID- 24213069 TI - The nonlinearity of offspring-parent regression for total sternopleural bristle number of Drosophila melanogaster. AB - A test of the linearity of the offspring-midparent regression for total sternopleural bristle number showed significant departure from linearity, with a tendency for higher heritability at higher values of the character. Offspring midparent regression coefficients for each of four subdivisions of the total range of bristle number were not significantly different. The nonlinearity of offspring-midparent regression detected in this study may be due to either chance effects, genotypic asymmetry of genes with large effect, distribution asymmetry, or a combination of these factors. Further work is required to determine the extent and causes of nonlinearity of offspring-parent regression. PMID- 24213070 TI - Mating systems of Cuphea laminuligera and Cuphea lutea. AB - In this paper, the mating systems of experimental populations of C. laminuligera and C. lutea are described. Outcrossing rates (t) were estimated for four populations of C. laminuligera and three populations of C. lutea using allozyme phenotypes of open-pollinated individual plant families. Populations were grown at densities of 1.0 * 1.0 m (low) and 0.04 * 0.3 m (high). Pollen and ovule frequencies and single locus and multilocus outcrossing rates were estimated for each population using the mixed-mating model. Multilocus estimates of t ranged from 0.83 to 0.98 and 1.00 to 1.01 for low and high density populations of C. laminuligera, respectively, and 0.17 to 0.26 and 0.36 to 0.54 for low and high density populations of C. lutea, respectively. C. laminuligera is predominantly allogamous; however, selfing rates as great as 17% were observed for this species. C. lutea is predominantly autogamous, but outcrossing rates as great as 54% were observed for this species. Outcrossing rates increased as density increased within C. lutea populations. PMID- 24213071 TI - General features of chromosome substitutions in Triticum aestivum x T. timopheevii hybrids. AB - Based on a C-banded chromosome analysis of Triticum aestivum x T. timopheevii hybrid lines, we developed a classification of the A(t) and G genome chromosomes that agrees with the standard genetic nomenclature of T. aestivum chromosomes. Transfer of genetic material from T. timopheevii to T. aestivum involved complete chromosomes, chromosome arms, or segments. Frequencies of chromosome substitution were highest for homoeologous group 2 and lowest for group 4. Moreover, B(G) substitutions were frequent compared to A(A(t)). The pattern of chromosome substitutions and rearrangements were unequal and depended on the genotype of the parental T. aestivum cultivar. PMID- 24213072 TI - Prediction of progeny variation in oat from parental genetic relationships. AB - The ability to predict agronomic performance of progeny from a cross would be a great benefit to plant breeders in selecting parents. The predictive value of parental genetic relationships estimating F1 progeny means and F4 family variances of nine argronomic traits was tested in 76 oat crosses, using genetic distance measures based on coefficients-of-parentage, quantitatively inherited morphological characters, and discretely inherited biochemical and morphological characters. Coefficients-of-parentage were better predictors of F1 performance than similarity measures derived from plant morphology or discretely inherited characters. Combined distance measures were better estimators of F1 specific combining ability (SCA) effects than any single measure. Among cultivars of similar adaptation and quantitative morphology, crosses between parents with high coefficients-of-parentage gave higher SCA effect values than crosses of distantly related parents for grain yield and total biomass. The opposite was found for crosses among cultivars of different adaptation or quantitative morphology. The best predictor of trait variances among F4 families was coefficients-of parentage. Crosses between more distantly related parents produced larger variances among families than crosses between closely related parents for plant biomass. For grain yield, test weight, heading date, grain filling period, and maturity date, crosses between more closely related parents produced larger among family variances than crosses of distantly related parents. Crosses between more distantly related parents involved at least one parent unadapted to central New York, and resulted in most of the progeny being generally unadapted. This, in part, may account for the low genetic variances for heading date, test weight, and grain yield in crosses of distantly related parents. PMID- 24213073 TI - Inheritance of chloroplast and mitochondrial DNA in Picea and composition of hybrids from introgression zones. AB - The cloning of white spruce (Picea glauca) mitochondrial DNA homologous to the cytochrome oxidase II and ATPasealpha genes of maize is described. These probes were used to define restriction fragment length polymorphisms which distinguish the white, Engelmann (P. engelmannii) and Sitka spruce (P. sitchensis) populations that occur in British Columbia. Analysis of progeny from crosses between the species revealed that mitochondrial DNA was maternally inherited in all cases (32 progeny from five independent crosses). The inheritance of chloroplast DNA was determined using a probe described previously; in this case, all progeny exhibited paternal inheritance (27 progeny from four crosses). Mitochondrial and chloroplast probes were used to test trees from zones of introgression between coastal (Sitka) and interior spruces (white and Engelmann). In most cases mitochondria and chloroplasts within individuals were contributed by different species. The data shows that there is a significant Sitka spruce component in trees east of the coastal watershed in British Columbia. PMID- 24213074 TI - The impact of domestication on the genetic variability in the orange carrot, cultivated Daucus carota ssp. sativus and the genetic homogeneity of various cultivars. AB - Isozyme analysis of wild and domesticated accessions indicated that domestication of the cultivated carrot Daucus carota ssp. sativus resulted in an insignificant reduction of all genetic variability and genetic distance estimates. Although they are less variable genetically, cultivated forms maintain a high proportion of observed heterozygosity. Relative to the overall genetic variability of the species, samples from four common cultivars 'Red Cored Chantenay', 'Scarlet Nantes', 'Danvers Half Long' and 'A Plus' demonstrated a high degree of genetic similarity. This is attributed to the recent development of orange cultivars and the limited gene pool utilized in their development. PMID- 24213075 TI - Alteration of reproductive effort by a monogenic, recessive mutation in jute (Corchorus capsularis L.). AB - Reproductive effort (RE) of a day-length neutral mutant TCJ-5, its parent, and two other cultivars of jute (Corchorus capsularis) was estimated as reproductive biomass/aerial biomass. Plant height at flowering and aerial biomass were significantly higher in the mutant, while the reproductive biomass at 55 days after flowering was statistically equal. Therefore, the estimated RE was significantly lower in the mutant compared to the parent and other cultivars. The lower RE of the mutant was due to delayed initiation of flowering and additional vegetative growth in this period. The results show alteration of RE by a recessive mutation. PMID- 24213076 TI - Reverse microemulsion-mediated synthesis of Bi2S3-QD@SiO2-PEG for dual modal CT fluorescence imaging in vitro and in vivo. AB - Monodispersed Bi2S3-QD@SiO2-PEG nanoparticles are prepared by a one-pot method in a reverse microemulsion system, which exhibited remarkable performances in CT and fluorescence imaging in vitro and in vivo. PMID- 24213077 TI - Alcohol-related presentations to the emergency department among young people: some concerns. PMID- 24213079 TI - Urine assessment in the critically ill: a matter of both quantity and quality. PMID- 24213080 TI - Implementing sedation protocols: closing the evidence-practice gap. PMID- 24213081 TI - The implementation of an analgesia-based sedation protocol reduced deep sedation and proved to be safe and feasible in patients on mechanical ventilation. AB - INTRODUCTION: Deep sedation in critically ill patients is associated with a longer duration of mechanical ventilation and a prolonged length of stay in the intensive care unit. Several protocols have been used to improve these outcomes. We implement and evaluate an analgesia-based, goal-directed, nurse-driven sedation protocol used to treat critically ill patients who receive mechanical ventilation. METHODS: We performed a prospective, two-phase (before-after), non randomized multicenter study that involved 13 intensive care units in Chile. After an observational phase (observational group, n=155), we designed, implemented and evaluated an analgesia-based, goal-directed, nurse-driven sedation protocol (intervention group, n=132) to treat patients who required mechanical ventilation for more than 48 hours. The primary outcome was to achieve ventilator-free days by day 28. RESULTS: The proportion of patients in deep sedation or in a coma decreased from 55.2% to 44.0% in the interventional group. Agitation did not change between the periods and remained approximately 7%. Ventilator-free days to day 28, length of stay in the intensive care unit and mortality were similar in both groups. At one year, post-traumatic stress disorder symptoms in survivors were similar in both groups. CONCLUSIONS: We designed and implemented an analgesia-based, goal-directed, nurse-driven sedation protocol in Chile. Although there was no improvement in major outcomes, we observed that the present protocol was safe and feasible and that it resulted in decreased periods of deep sedation without increasing agitation. PMID- 24213082 TI - Urinary strong ion difference is a major determinant of plasma chloride concentration changes in postoperative patients. AB - OBJECTIVE: To show that alterations in the plasma chloride concentration ([Cl ]plasma) during the postoperative period are largely dependent on the urinary strong ion difference ([SID]urine=[Na+]urine+[K+]urine-[Cl-]urine) and not on differences in fluid therapy. METHODS: Measurements were performed at intensive care unit admission and 24 hours later in a total of 148 postoperative patients. Patients were assigned into one of three groups according to the change in [Cl ]plasma at the 24 hours time point: increased [Cl-]plasma (n=39), decreased [Cl ]plasma (n=56) or unchanged [Cl-]plasma (n=53). RESULTS: On admission, the increased [Cl-]plasma group had a lower [Cl-]plasma (105 +/- 5 versus 109 +/- 4 and 106 +/- 3 mmol/L, p<0.05), a higher plasma anion gap concentration ([AG]plasma) and a higher strong ion gap concentration ([SIG]). After 24 hours, the increased [Cl-]plasma group showed a higher [Cl-]plasma (111 +/- 4 versus 104 +/- 4 and 107 +/- 3 mmol/L, p<0.05) and lower [AG]plasma and [SIG]. The volume and [SID] of administered fluids were similar between groups except that the [SID]urine was higher (38 +/- 37 versus 18 +/- 22 and 23 +/- 18 mmol/L, p<0.05) in the increased [Cl-]plasma group at the 24 hours time point. A multiple linear regression analysis showed that the [Cl-]plasma on admission and [SID]urine were independent predictors of the variation in [Cl-]plasma 24 hours later. CONCLUSIONS: Changes in [Cl-]plasma during the first postoperative day were largely related to [SID]urine and [Cl-]plasma on admission and not to the characteristics of the infused fluids. Therefore, decreasing [SID]urine could be a major mechanism for preventing the development of saline-induced hyperchloremia. PMID- 24213083 TI - Anion gap corrected for albumin, phosphate and lactate is a good predictor of strong ion gap in critically ill patients: a nested cohort study. AB - OBJECTIVE: Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality. METHODS: We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2 mEq/L (low BE group - lBE) and the other in patients with base-excess >-2 mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality. RESULTS: There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r2=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r2=0.94) and in the hBE group (r2=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression. CONCLUSION: Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality. PMID- 24213084 TI - Association between the rapid shallow breathing index and extubation success in patients with traumatic brain injury. AB - OBJECTIVE: To investigate the association between the rapid shallow breathing index and successful extubation in patients with traumatic brain injury. METHODS: This study was a prospective study conducted in patients with traumatic brain injury of both genders who underwent mechanical ventilation for at least two days and who passed a spontaneous breathing trial. The minute volume and respiratory rate were measured using a ventilometer, and the data were used to calculate the rapid shallow breathing index (respiratory rate/tidal volume). The dependent variable was the extubation outcome: reintubation after up to 48 hours (extubation failure) or not (extubation success). The independent variable was the rapid shallow breathing index measured after a successful spontaneous breathing trial. RESULTS: The sample comprised 119 individuals, including 111 (93.3%) males. The average age of the sample was 35.0 +/- 12.9 years old. The average duration of mechanical ventilation was 8.1 +/- 3.6 days. A total of 104 (87.4%) participants achieved successful extubation. No association was found between the rapid shallow breathing index and extubation success. CONCLUSION: The rapid shallow breathing index was not associated with successful extubation in patients with traumatic brain injury. PMID- 24213085 TI - Functional and psychological features immediately after discharge from an intensive care unit: prospective cohort study. AB - OBJECTIVE: To assess the functional and psychological features of patients immediately after discharge from the intensive care unit. METHODS: Prospective cohort study. Questionnaires and scales assessing the degree of dependence and functional capacity (modified Barthel and Karnofsky scales) and psychological problems (Hospital Anxiety and Depression Scale), in addition to the Epworth Sleepiness Scale, were administered during interviews conducted over the first week after intensive care unit discharge, to all survivors who had been admitted to this service from August to November 2012 and had remained longer than 72 hours. RESULTS: The degree of dependence as measured by the modified Barthel scale increased after intensive care unit discharge compared with the data before admission (57 +/- 30 versus 47 +/- 36; p < 0.001) in all 79 participants. This impairment was homogeneous among all the categories in the modified Barthel scale (p < 0.001) in the 64 participants who were independent or partially dependent (Karnofsky score >= 40) before admission. The impairment affected the categories of personal hygiene (p = 0.01) and stair climbing (p = 0.04) only in the 15 participants who were highly dependent (Karnofsky score < 40) before admission. Assessment of the psychological changes identified mood disorders (anxiety and/or depression) in 31% of the sample, whereas sleep disorders occurred in 43.3%. CONCLUSIONS: Patients who remained in an intensive care unit for 72 hours or longer exhibited a reduced functional capacity and an increased degree of dependence during the first week after intensive care unit discharge. In addition, the incidence of depressive symptoms, anxiety, and sleep disorders was high among that population. PMID- 24213086 TI - Nursing workload in public and private intensive care units. AB - OBJECTIVE: This study sought to compare patients at public and private intensive care units according to the nursing workload and interventions provided. METHODS: This retrospective, comparative cohort study included 600 patients admitted to 4 intensive care units in Sao Paulo. The nursing workload and interventions were assessed using the Nursing Activities Score during the first and last 24 hours of the patient's stay at the intensive care unit. Pearson's chi-square test, Fisher's exact test, the Mann-Whitney test, and Student's t test were used to compare the patient groups. RESULTS: The average Nursing Activities Score upon admission to the intensive care unit was 61.9, with a score of 52.8 upon discharge. Significant differences were found among the patients at public and private intensive care units relative to the average Nursing Activities Score upon admission, as well as for 12 out of 23 nursing interventions performed during the first 24 hours of stay at the intensive care units. The patients at the public intensive care units exhibited a higher average score and overall more frequent nursing interventions, with the exception of those involved in the "care of drains", "mobilization and positioning", and "intravenous hyperalimentation". The groups also differed with regard to the evolution of the Nursing Activities Score among the total case series as well as the groups of survivors from the time of admission to discharge from the intensive care unit. CONCLUSION: Patients admitted to public and private intensive care units exhibit differences in their nursing care demands, which may help managers with nursing manpower planning. PMID- 24213087 TI - Correlation of the EuroSCORE with the onset of postoperative acute kidney injury in cardiac surgery. AB - OBJECTIVE: The objective of this study was to assess the correlation between the European System for Cardiac Operative Risk Evaluation (EuroSCORE) score and the risk of developing acute kidney injury in cardiac surgery patients. METHODS: This retrospective study was conducted at a tertiary hospital on consecutive cardiac surgery patients (e.g., valvular, ischemic and congenital heart diseases) between October 2010 and July 2011. RESULTS: One hundred patients were assessed. Among the 100 patients, six were excluded, including five because of prior kidney disease or dialysis therapy and one because of incomplete medical records. The primary surgical indications were myocardial revascularization in 55 patients (58.5% of cases) and valve replacement in 28 patients (29.8%). According to the EuroSCORE, 55 patients were classified as high risk (58.5%), 27 patients as medium risk (28.7%) and 12 patients as low risk (12.8%). In the postoperative period, patients were classified with the Risk, Injury, Failure, Loss and End stage kidney disease (RIFLE) score. Among the 31 patients (33%) who displayed an increase in serum creatinine, 18 patients (19.1%) were classified as RIFLE "R" (risk), seven patients (7.4%) were classified as RIFLE "I" (injury) and six patients (6.5%) were classified as RIFLE "F" (failure). Among the patients who were considered to be high risk according to the EuroSCORE criteria, 24 patients (43.6%) showed acute kidney injury. Among the patients who were classified as medium or low risk, acute kidney injury occurred in 18.5 and 16.6% of the cases, respectively. The correlations between risk stratification (low, medium and high) and the EuroSCORE and postoperative RIFLE scores were statistically significant (p=0.03). CONCLUSION: In the studied population, there was a statistically significant correlation between the EuroSCORE and the risk of developing acute kidney injury in the postoperative period after cardiac surgery. PMID- 24213088 TI - Healthcare associated infections caused by coagulase-negative Staphylococci in a neonatal intensive care unit. AB - OBJECTIVE: This study sought to evaluate infections related to health care caused by coagulase-negative Staphylococci in a neonatal intensive care unit by assessing antimicrobial susceptibility profiles and potentially effective antibiotic regimens. METHODS: This was a retrospective descriptive study performed on a case series of healthcare-associated infections, and the antimicrobial susceptibility profiles were evaluated. Newborns from other hospitals who were admitted to a neonatal intensive care unit in Rio de Janeiro between January 1, 2010, and June 30, 2012, were studied. RESULTS: In total, 765 patients were admitted, totaling 3,051 patient-days, and the incidence density of general infection was 18.9 per 1,000 patient-days. The rate of central venous catheter use was 71.6%, and the positive culture rate for all sites and all infections related to health care were 68.4%. Coagulase-negative Staphylococci were identified in 11 (19.2%) of 57 health care-related infections, and infections with extended-spectrum beta-lactamase producing Klebsiella pneumoniae and Candida sp. constituted 5 cases each. Of the 11 cases of coagulase-negative Staphylococci, 10 (90.9%) were primary bloodstream infections. The sensitivity of the coagulase-negative Staphylococci isolates to vancomycin, clindamycin, ciprofloxacin, oxacillin and gentamycin was 100%, 81.8%, 72.7%, 27.2% and 22.2%, respectively. There were no deaths directly attributed to coagulase-negative Staphylococci infection. CONCLUSION: Coagulase-negative Staphylococci was the main agent identified in healthcare-associated infections, with low rates of infections related to central venous catheter. In hospitals with a high oxacillin resistance profile, similar to those included in this study, vancomycin may be used as an initial therapy, although clindamycin represents a viable alternative. PMID- 24213089 TI - Early nasal injury resulting from the use of nasal prongs in preterm infants with very low birth weight: a pilot study. AB - OBJECTIVE: To analyze the incidence of early-onset nasal injury in infants with very low birth weight and indication for noninvasive ventilation via nasal prongs. METHODS: A prospective case series of infants with gestational age <37 weeks, weight <1.500 g and postnatal age <29 days. The patients were evaluated three times daily from the installation of nasal prongs to the 3rd day of use. The patients' clinical conditions and the device's characteristics and its application were analyzed. The initial analysis was descriptive, indicating the prevalence of nasal injury and factors associated with it. Categorical data were analyzed using the chi-squared test or Fisher's exact test, and numerical data were analyzed using the t-test or the Mann-Whitney test. RESULTS: Eighteen infants were included; 12 (with a gestational age of 29.8 +/- 3.1 weeks, birth weight of 1.070 +/- 194 g and a Score for Neonatal Acute Physiology - Perinatal Extension (SNAPPE) of 15.4 +/- 17.5) developed nasal injuries (injury group), and 6 (with a gestational age of 28.0 +/- 1.9 weeks, weight of 1.003 +/- 317 g and SNAPPE of 26.2 +/- 7.5) showed no nasal injury (uninjured group). The injury group subjects were more often male (75% versus 17%), and their injuries appeared after an average of 18 hours, predominantly during the night (75%). CONCLUSION: The incidence of nasal injury in preterm infants who experienced noninvasive ventilation via nasal prongs was high, and a study of associated factors may be planned based on this pilot. PMID- 24213090 TI - Impact of renal replacement therapy on the respiratory function of patients under mechanical ventilation. AB - OBJECTIVE: To assess the oxygenation behavior and ventilatory mechanics after hemodialysis in patients under ventilatory support. METHODS: The present study was performed in the general intensive care unit of a tertiary public hospital. Patients over 18 years of age under mechanical ventilation and in need of dialysis support were included. Each patient was submitted to 2 evaluations (pre- and post-dialysis) regarding the cardiovascular and ventilatory parameters, the ventilatory mechanics and a laboratory evaluation. RESULTS: Eighty patients with acute or chronic renal failure were included. The analysis of the ventilatory mechanics revealed a reduction in the plateau pressure and an increased static compliance after dialysis that was independent of a reduction in blood volume. The patients with acute renal failure also exhibited a reduction in peak pressure (p=0.024) and an increase in the dynamic compliance (p=0.026), whereas the patients with chronic renal failure exhibited an increase in the resistive pressure (p=0.046) and in the resistance of the respiratory system (p=0.044). The group of patients with no loss of blood volume after dialysis exhibited an increase in the resistive pressure (p=0.010) and in the resistance of the respiratory system (p=0.020), whereas the group with a loss of blood volume >2,000 mL exhibited a reduction in the peak pressure (p=0.027). No changes in the partial pressure of oxygen in arterial blood (PaO2) or in the PaO2/the fraction of inspired oxygen (PaO2/FiO2) ratio were observed. CONCLUSION: Hemodialysis was able to alter the mechanics of the respiratory system and specifically reduced the plateau pressure and increased the static compliance independent of a reduction in blood volume. PMID- 24213091 TI - Manual hyperinflation in airway clearance in pediatric patients: a systematic review. AB - OBJECTIVE: To perform an assessment of the available literature on manual hyperinflation as a respiratory physical therapy technique used in pediatric patients, with the main outcome of achieving airway clearance. METHODS: We reviewed articles included in the Lilacs (Latin American and Caribbean Literature on Health Sciences/Literatura Latino Americana e do Caribe em Ciencias da Saude), Cochrane Library, Medline (via Virtual Health Library and PubMed), SciELO (Scientific Electronic Library), and PEDro (Physiotherapy Evidence Database) databases from 2002 to 2013 using the following search terms: "physiotherapy (techniques)", "respiratory therapy", "intensive care", and "airway clearance". The selected studies were classified according to the level of evidence and grades of recommendation (method of the Oxford Centre for Evidence-Based Medicine) by two examiners, while a third examiner repeated the search and analysis and checked the classification of the articles. RESULTS: Three articles were included for analysis, comprising 250 children (aged 0 to 16 years). The main diagnoses were acute respiratory failure, recovery following heart congenital disease and upper abdominal surgery, bone marrow transplantation, asthma, tracheal reconstruction, brain injury, airway injury, and heterogeneous lung diseases. The studies were classified as having a level of evidence 2C and grade of recommendation C. CONCLUSIONS: Manual hyperinflation appeared useful for airway clearance in the investigated population, although the evidence available in the literature remains insufficient. Therefore, controlled randomized studies are needed to establish the safety and efficacy of manual hyperinflation in pediatric patients. However, manual hyperinflation must be performed by trained physical therapists only. PMID- 24213092 TI - Implementation of a personalized workplace smoking cessation programme. AB - BACKGROUND: Providing smoking cessation programmes through workplaces is an effective method of assisting employees to quit smoking; however, few employers provide such services, and achieving long-term success remains challenging. AIMS: To evaluate the effectiveness of a workplace-based tailored smoking cessation programme that combined telephone-based counselling with group behaviour therapy sessions in helping employees to quit. METHODS: A smoking cessation programme was offered to employees of a large corporation that is respons ible for the passenger rail network in New South Wales (NSW), Australia. Two hundred and thirty participants enrolled in the programme, which offered telephone-based coaching and group sessions designed around cognitive behavioural therapy principles. One hundred and eight participants (47%) completed the 6 month follow up assessment. RESULTS: Of the estimated 2850 smokers in the organization, 8% (230) registered for the smoking cessation programme, with 77% (176) participating in telephone-based coaching and/or group sessions. Intention-to treat analysis indicated 22% of participants achieved 7 day point prevalence abstinence and 10% achieved 3 month prolonged abstinence at the 6 month follow up. Over 75% of those still smoking at follow-up reported intentions to quit in the next 6 months. Psychological distress was also significantly lower at 6 month follow-up. Participants reported high levels of satisfaction with the programme. CONCLUSIONS: The smoking cessation programme successfully assisted employees to quit smoking. Unique aspects of the programme such as continuity of care were valued by participants and may have contributed to the programme's success. PMID- 24213093 TI - Evaluation of a musculoskeletal training package for occupational health practitioners. AB - BACKGROUND: Musculoskeletal disorders (MSDs) are a common cause of disability in the workplace. Despite this, there is known to be a wide variation in the assessment of MSDs by UK occupational health (OH) professionals. Therefore we developed a workshop, supported by a bespoke, on-line video, focussing on the assessment and management of MSDs. AIMS: To assess the impact of the training package on the knowledge, confidence and reported behaviour of attendees. METHODS: Workshops were held in two regional centres in England. Delegates completed a questionnaire on arrival to establish their baseline knowledge and confidence and again at the end of the training. A third questionnaire, with one reminder, was e-mailed to delegates 4 months following the workshops. RESULTS: Ninety-two OH professionals (77 nurses, 10 doctors and 5 'others') attended and more than 80% reported that they had no previous training in examining the upper or lower limb or in distinguishing specific from non-specific MSDs. Confidence among delegates in examination, diagnosis and management of MSDs improved after the workshop and these changes were sustained and remained statistically significant from baseline 4 months afterwards. Following the training, 79% (50) of delegates reported that they had shared the knowledge and skills acquired with their colleagues and 71% reported that they had used the examination techniques in their day-to-day practice. CONCLUSIONS: We have developed a training package which resulted in improved knowledge among attendees and gave them confidence to use their skills in practice. PMID- 24213094 TI - How do GPs complete fit note comments? AB - BACKGROUND: The 'fit note' was introduced in the UK in April 2010, to facilitate return to work (RTW). However, no research to date has reported on how general practitioners (GPs) complete the comments section of the fit note. AIMS: To investigate the content of GPs' comments in a sample of actual fit notes. METHODS: Data were collected in a service evaluation of fit notes issued by a regular general practice and those issued by a fit for work service (FFWS), where the fit notes for patients using the service are signed by GPs who have completed or are studying for a Diploma in Occupational Medicine. Content analysis was conducted on the fit note comments. RESULTS: There were 1212 fit notes available for analysis. Seven hundred and twelve were issued by the general practice and 500 by the FFWS. The FFWS made comments in 98% of those who may be fit and 90% of those not fit against 72% and 12%, respectively, for comments by the general practice. Fourteen different categories were identified in the comments. Most comments made some reference to RTW but few described the functional effects of the patient's condition. Comments frequently covered more than one category and appeared to be serving a number of different purposes. CONCLUSIONS: There was a wide variety in how the comments section was completed, and GPs were not completing the fit note as intended. The information provided may require improvement if it is to be useful to employers. PMID- 24213095 TI - Under reporting of road traffic injuries in the district of Kandy, Sri Lanka. AB - OBJECTIVES: To conduct a community survey to estimate the degree to which road traffic injuries (RTIs) are under reported and to compare the characteristics of RTI reported to the police to those not reported. DESIGN: A cross-sectional population-based study. SETTING: Kandy district, Sri Lanka. PARTICIPANTS: RTIs and deaths during the preceding 12 months were identified through a community based cross-sectional survey with a sample size of 3080 households. A stratified multistage cluster sampling with population proportion to size was used. 'Events reported' to the police were cross checked against events in the police records of the given or adjacent police stations, and either were 'Events found' or 'Not found'. 'Under reported' included those 'Not reported' and those reported but 'Not found' in the police dataset. RESULTS: Information about 11 724 persons were obtained from 3080 households, identifying 149 persons who suffered an RTI. Of these, 57% were 'Events reported', and of these 43.6% (n=65) were 'Events found' in police records (95% CI, 36.0 to 51.6). There were 42 events 'Not reported' to police while an additional 7 were 'Not found' in the police records of the given police station. Although they were claimed to have been reported to the police, 33% (95% CI 25.8 to 40.7) were 'Under reported'. There were significant differences in age (p=0.02), family income (p<0.001), road user type (p=0.001), injury severity (p<0.001) and injury category (p=0.01) between 'Events found' in the police records and 'Under reported' events. CONCLUSIONS: In the Kandy district, 33% of RTIs were 'under reported'. These findings could be used as evidence for policy planning to prevent RTIs, and highlights the need for a nation-wide community-based survey to determine the true rates of RTI for a better understanding of the reasons for under reporting. PMID- 24213096 TI - Hyperuricemia is independently associated with endothelial dysfunction in postmenopausal women but not in premenopausal women. AB - OBJECTIVES: The purpose of this study was to determine the relationships between uric acid, endothelial function and cardiovascular risk factors and to investigate whether menopausal status was associated with the relationship between uric acid and endothelial function in women. DESIGN: Cross-sectional study. SETTING: 3 general hospitals in Japan. PARTICIPANTS: 749 Japanese women aged 30-74 years recruited from people who underwent health-screening examinations with agreement for measurement of vascular function. MEASURES: We measured serum concentrations of uric acid and flow-mediated vasodilation (FMD). Percentage of FMD (peak diameter-baseline diameter/baseline diameter) was used for analysis. Endothelial dysfunction was defined as FMD <=4.90%, division point for the lowest tertile and the middle tertile of FMD. Menopause women were defined as participants without menstruation for over 1 year or participants with a history of hysterectomy or bilateral oophorectomy. RESULTS: Of the 749 participants, 368 (49.1%) were premenopausal women and 381 (50.9%) were postmenopausal women. Age, body mass index, systolic blood pressure, total cholesterol, triglycerides, glucose, estimated glomerular filtration rate and Framingham risk score were significantly correlated with serum uric acid level. FMD showed a gradual decrease in accordance with the serum uric acid level in the entire study population (<4 mg/dL, 6.85+/-3.65%; 4 to <5 mg/dL, 6.79+/-3.60%; 5 to <6 mg/dL, 6.24+/-3.58%; >=6 mg/dL, 5.27+/-3.18%; p=0.01). Multivariate analysis revealed that uric acid was a significantly independent risk factor for endothelial dysfunction in postmenopausal women (OR 1.23, 95% CI 1.01 to 1.50), but not in premenopausal women. CONCLUSIONS: These findings suggest that uric acid can be used as a risk marker of endothelial dysfunction in a female population, and particularly as an independent risk factor in postmenopausal women but not in premenopausal women. REGISTRATION NUMBER OF THE STUDY: UMIN000003409. PMID- 24213097 TI - Lymph node metastasis in patients with epithelial ovarian cancer macroscopically confined to the ovary: review of a single-institution experience. AB - BACKGROUND: To evaluate the patterns of lymphatic spread in epithelial ovarian cancer (EOC) macroscopically confined to the ovary and to determine risk factors for lymph node metastasis. MATERIALS AND METHODS: All patients with clinically apparent stage IA/B/C EOCs who underwent staging surgery between January 2003 and February 2013 were retrospectively identified. RESULTS: Two hundred and thirty six (n = 236) consecutive patients were operated for primary epithelial ovarian carcinoma. Sixty-two of these patients (26.2 %) who underwent a comprehensive staging procedure including pelvic and paraaortic lymphadenectomy were diagnosed with tumors confined to one or two ovaries (stage IA/B/C). Of these 62 patients, 17 (27.4 %) had upstaged disease and 8 (12.9 %) had lymph node metastasis. Tumor histology was serous in 25 patients (40.3 %), mucinous in 23 patients (37 %), endometrioid in 9 patients (14.5 %), and clear cell in 5 patients (8 %). Positive lymph node status was found in 20 % (5/25) of those with serous histology while this rate was only 8.1 % (3/37) in those with non-serous disease. Although the presence of ascites was not associated with an increased risk of lymph node involvement (p = 0.24), positive peritoneal cytology (p = 0.001) and grade 3 disease (p = 0.001) were significant predictors of lymph node involvement. CONCLUSION: All patients diagnosed with EOC macroscopically confined to the ovary should be considered for comprehensive staging surgery including pelvic and paraaortic lymphadenectomy. PMID- 24213098 TI - Emergency peripartum hysterectomy: our 12-year experience. AB - OBJECTIVE: The aim of this study was to determine the incidence, indications and the risk factors and complications of emergency peripartum hysterectomy (EPH). METHODS: We analyzed retrospectively 44 cases of EPH performed at tertiary obstetric center between January 2001 and April 2013. Data related to demographics, reproductive histories, indications for EPH, and postoperative follow-up were obtained by analyses of hospital records. RESULTS: The overall incidence of EPH was 0.48 per 1,000 deliveries during the study period. The most common indications of EPH were abnormal placentation (50 %), uterine atony (36 %) and uterine rupture (9 %). All patients who underwent EPH with abnormal placentation had one or more previous cesarean sections (CS) except one. In our series, 24 cases (54 %) underwent total hysterectomy, most of which had the diagnosis of abnormal placentation (75 %), whereas subtotal hysterectomy was the choice of management of bleeding in cases with uterine atony (60 %). Maternal mortality was seen in 2 patients (4.5 %). The causes were disseminated intravascular coagulation in one and adult respiratory distress syndrome in the other patient. Perinatal mortality was observed in 7 patients (16 %). The causes for perinatal mortality were placental abruption in 4 and prematurity in 3 patients. CONCLUSIONS: In our series, abnormal placentation was the most common indication for EPH. The risk factors for EPH were previous CS for abnormal placentation and placental abruption for uterine atony and peripartum hemorrhage. Limiting the number of CS deliveries would bring a significant impact on decreasing the risk of EPH. PMID- 24213099 TI - Natural populations of bacteria in Lake Kinneret: Observations with scanning electron and epifluorescence microscopy. AB - The bacterioplankton assemblage in Lake Kinneret, Israel, sampled on 6 occasions representative of different seasonal conditions was studied with scanning electron microscopy (SEM) and epifluorescence microscopy after acridine-orange staining. In near-surface (1-3 m) samples taken in October 1981 and March 1983, several unusual types of budding, appendaged, and filamentous cells were found. During lake stratification, typical large anaerobic forms (including photosynthetic green sulphur bacteria) were observed in samples from the metalimnion and deep (40 m) hypolimnion. Epifluorescence counts indicated that bacteria in the water column ranged from 0.55 to 2.67 * 10(6) cells ml(-1). PMID- 24213100 TI - Bacterial growth on dissolved organic carbon from a blackwater river. AB - Different nominal molecular weight (nMW) fractions of DOC from a southeastern blackwater river were concentrated by ultrafiltration and added to sieved river water to assess each fraction's ability to stimulate bacterial growth. Bacterial growth was measured using change in bacterial biomass from direct counts and using(3)H-thymidine incorporated into DNA. Bacterial growth and amount of DOC used was greatest in the low MW enrichment (< 1,000 nMW) and least in the intermediate MW enrichment (1,000-10,000 nMW). The high MW fraction (> 10,000 nMW) supported more growth than did the intermediate MW fraction, apparently because of lower MW compounds complexed with a high MW refractory core. The low MW fraction of DOC from a clearwater mountain stream, a boreal blackwater river, and leachate from water oak and willow leaves also stimulated more bacterial growth than did other fractions. However, the high MW DOC from these other sources was not as biologically available as high MW DOC from a blackwater river. Bacteria converted blackwater river DOC to bacterial biomass with an efficiency of 31%. Bacteria produced at the expense of abundant riverine DOC provide a trophic resource for protozoa and higher levels of the microbial food web of a blackwater river. PMID- 24213101 TI - A mathematical model for the growth of bacterial microcolonies on marine sediment. AB - Counts of bacterial microcolonies attached to deep-sea sediment particles showed 4-, 8-, 16-, and 32-celled microcolonies to be very rare. This was investigated with a mathematical model in which microcolonies grew from single cells at a constant growth rate (MU), detached from particles at constant rate (lambda), and reattached as single cells. Terms for attachment of foreign bacteria (a) and death of single cells (d) were also included. The best method of fitting the model to the microcolony counts was a weighted least-squares approach by whichlambda(0.83 hour(-1)) was estimated to be about 20 times greater thanMU(0.038 hour(-1)). This showed that the bacteria were very mobile between sediment particles and this mobility was explained in terms of attachment by reversible sorption. The implications of the results for the frequency of dividing cell method for estimating growth rates of sediment bacteria are discussed. The ratio oflambda andMU was found to be very robust both in terms of the errors associated with the microcolony counts and the range of microcolony sizes used to obtain the solution. PMID- 24213102 TI - Degradation of substituted thiophenes by bacteria isolated from activated sludge. AB - Actinomycetes were isolated from activated sludge acclimated to thiophene-2 carboxylic acid (T2C) or 5-methyl-thiophene-2-carboxylic acid (T5M2C). These isolates were apparently identical and were identified as strains ofRhodococcus. The strains could grow on T2C, T5M2C, or thiophene-2-acetic acid as sole sources of carbon and energy, but could not use thiophene, methyl thiophenes, several other substituted thiophenes, dibenzothiophene, dimethyl sulfide, or pyrrole-2 carboxylic acid. T2C was degraded quantitatively to sulfate, and its carbon was converted almost entirely to cell biomass and carbon dioxide. Growth yields indicated about 25% conversion of T2C-carbon to cell-carbon. Growth was not supported by thiosulfate or methionine, nor were these compounds oxidized.Rhodococcus strain TTD-1 grown on T2C oxidized both T2C and T5M2C with an apparent Km of 1.3*10(-5) M. Sulfide was also oxidized by T2C-grown organisms. This is the first demonstration of an actinomycete capable of the complete degradation of thiophene derivatives and of their use by it as sole substrates for growth. PMID- 24213103 TI - Viability of soil bacteria: Optimization of plate-counting technique and comparison between total counts and plate counts within different size groups. AB - Viable counts of heterotropic soil bacteria were 3-5 times higher on low-nutrient agar media compared with a series of conventional agar media. Substantial amounts of monosaccharides and amino acids were present in solid media made from distilled water and agar powder, and a salt-solution agar medium (without organic substrates added) gave practically the same colony counts as the low nutrient soil extract agar medium. MPN values were comparable to or lower than plate counts. A search for slow-growing cells in the negative MPN tubes by fluorescence microscopical examination after 3 months incubation was negative.The viable counts were 2-4% of the total microscopical counts in different soils. Assuming that the colony-forming cells did not derive from the numerous "dwarf" cells present in soil, a calculated percent viability of the larger cells was about 10%. The ecological significance of the plate-counting technique is discussed. PMID- 24213104 TI - Seasonal variations in abundance and activity of nitrifiers in four arable cropping systems. AB - Ammonium and nitrite oxidizers were counted with the most probable number (MPN) method and potential ammonium- and nitrite-oxidation rates were determined with a chlorate inhibition technique in an arable soil over a 3-year period. Samples were taken from the topsoil once a month for 2 years and a few times during a third year in four cropping systems: unfertilized lucerne ley and barley, and nitrate fertilized grass ley and barley. The distribution of nitrifiers was determined and their activities measured at various soil depths and between and within plant rows of fertilized barley.The numbers and activities of ammonium oxidizers were highest in the spring and autumn samples. Numbers of ammonium oxidizers ranged from 0.2 to 19*10(4) and nitrite oxidizers from 3 to 870*10(4) cells g(-1) dry soil. Potential ammonium-oxidizer activities ranged from 120 to 1,060 and nitrite-oxidizer activities ranged from 280 to 680 ng N g(-1) dry soil hour(-1). Lucerne and grass leys generally showed the highest, whereas unfertilized barley had the lowest, abundances and activities.Abundance estimates and activities were 10-20 times higher in the plow layer than in underlying sand and clay layers. A strong correlation was found between organic matter content vs numbers and activities of both ammonium and nitrite oxidizers. Only nitrite oxidizer counts were significantly higher within plant rows compared to between plant rows. PMID- 24213105 TI - Quantification of predatory and endoparasitic nematophagous fungi in soil. AB - Methods were developed to quantify predatory and endoparasitic fungi in soil. The methods were based on previously developed detection techniques and combined with a most probable number estimation. The methods were applied to an agricultural soil fertilized with farmyard manure. Large amounts of farmyard manure resulted in increased amounts of organic matter, numbers of propagules of predatory and endoparasitic fungi, and numbers of bacteria and nematodes. PMID- 24213106 TI - The decline and fall of the art of teaching? PMID- 24213107 TI - DNA Methylation and the HOXC6 Paradox in Prostate Cancer. AB - Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNTN1 (encoding a cell adhesion protein), DKK3 and WIF1 (encoding WNT growth factor antagonists) as well as DNA methylation of DKK3 and WIF1. HOXC6 upregulation and association with poor prognosis were confirmed in our tissue series. The three target genes were each significantly downregulated in cancer tissues and expression of each one correlated inversely with that of HOXC6. Cases with lower WIF1 expression showed significantly earlier recurrence (p = 0.021), whereas no statistical significance was reached for CNTN1 and DKK3. Hypermethylation of DKK3 or WIF1 gene promoters was observed in a subset of cancers with downregulated expression, but was often weak. Our data support the hypothesis that HOXC6 target genes exerting tumor-suppressive effects are epigenetically downregulated in prostate cancer, but DNA methylation appears to follow or bolster rather than to cause their transcriptional inactivation. PMID- 24213108 TI - Infiltration of m2 tumor-associated macrophages in oral squamous cell carcinoma correlates with tumor malignancy. AB - Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163+ cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4+ and CD8+ T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163+ TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC. PMID- 24213110 TI - Inhibitory Effect of a gamma-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice. AB - In the present study, we determined the effects of a gamma-tocopherol-rich mixture of tocopherols (gamma-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary gamma-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of gamma-TmT was stronger than alpha tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary gamma-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that g-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of g-TmT increased the levels of a-, gamma- and delta- tocopherol in plasma, and increased levels of gamma- and delta- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that g-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of g TmT for prostate cancer in humans. PMID- 24213109 TI - Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma. AB - Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression. PMID- 24213111 TI - Biomarkers in prostate cancer epidemiology. AB - Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. PMID- 24213113 TI - The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer. AB - Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT2 ) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT2 receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT2-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT2-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence. PMID- 24213112 TI - Combined hyperthermia and radiotherapy for the treatment of cancer. AB - Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in-tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, car diac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threat-ening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy. PMID- 24213114 TI - Targeted radionuclide therapy. AB - Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose. PMID- 24213116 TI - The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer. AB - Colorectal cancer (CRC) is now the second-leading cause of cancer deaths in the USA. Colorectal cancer progression and metastasis depends on the orchestration of the aberrant signaling pathways that control tumor cell proliferation, survival and migration/invasion. Epidemiological, clinical, and animal studies have demonstrated that prostaglandin-endoperoxide synthase 2 (PTGS2) and epithelial growth factor (EGF) signaling pathways play key roles in promoting colorectal cancer growth and metastasis. In this review, we highlight major advances in our understanding of the roles of PTGS2 and EGF signaling in colorectal cancer. PMID- 24213117 TI - Forced Expression of ZNF143 Restrains Cancer Cell Growth. AB - We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1), aurora kinase B (AURKB) and some minichromosome maintenance complex components (MCM). However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells) and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division. PMID- 24213115 TI - Cytokines in cancer immunotherapy. AB - Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines. PMID- 24213120 TI - Helical tomotherapy in children and adolescents: dosimetric comparisons, opportunities and issues. AB - Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1 24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory. PMID- 24213119 TI - Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells. AB - Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells. PMID- 24213121 TI - Peptide Based Vaccine Approaches for Cancer-A Novel Approach Using a WT-1 Synthetic Long Peptide and the IRX-2 Immunomodulatory Regimen. AB - Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors including choice of immunogenic cancer rejection antigens, optimization of vaccine platforms and immune adjuvants to effectively polarize the immune response, and incorporation of strategies to reverse cancer mediated immune suppression by utilization of effective adjuvant/immune modulators. WT-1 (Wilms' tumor gene 1) is a cancer antigen that is required for tumorigenesis, expressed in a high percentage of tumor cells and rarely expressed in adult normal cells. Moreover spontaneous immunity to WT-1 is seen in cancer patients and can be augmented with various therapeutic vaccine approaches. IRX-2 is an immune modulator with demonstrated preclinical and clinical pleiotropic immune activities including enhancement of the immune response to potential tumor antigens. This paper presents the rationale and preclinical data for utilizing the WT-1 tumor antigen in a novel vaccine platform consisting of a synthetic long peptide containing multiple class I and class II epitopes in combination with the IRX-2 immunomodulatory regimen to overcome immuno-suppressive pathways and enhance the anti-tumor response. PMID- 24213118 TI - Inducible hsp70 in the regulation of cancer cell survival: analysis of chaperone induction, expression and activity. AB - Understanding the mechanisms that control stress is central to realize how cells respond to environmental and physiological insults. All the more important is to reveal how tumour cells withstand their harsher growth conditions and cope with drug-induced apoptosis, since resistance to chemotherapy is the foremost complication when curing cancer. Intensive research on tumour biology over the past number of years has provided significant insights into the molecular events that occur during oncogenesis, and resistance to anti-cancer drugs has been shown to often rely on stress response and expression of inducible heat shock proteins (HSPs). However, with respect to the mechanisms guarding cancer cells against proteotoxic stresses and the modulatory effects that allow their survival, much remains to be defined. Heat shock proteins are molecules responsible for folding newly synthesized polypeptides under physiological conditions and misfolded proteins under stress, but their role in maintaining the transformed phenotype often goes beyond their conventional chaperone activity. Expression of inducible HSPs is known to correlate with limited sensitivity to apoptosis induced by diverse cytotoxic agents and dismal prognosis of several tumour types, however whether cancer cells survive because of the constitutive expression of heat shock proteins or the ability to induce them when adapting to the hostile microenvironment remains to be elucidated. Clear is that tumours appear nowadays more "addicted" to heat shock proteins than previously envisaged, and targeting HSPs represents a powerful approach and a future challenge for sensitizing tumours to therapy. This review will focus on the anti-apoptotic role of heat shock 70kDa protein (Hsp70), and how regulatory factors that control inducible Hsp70 synthesis, expression and activity may be relevant for response to stress and survival of cancer cells. PMID- 24213122 TI - Role of radiation therapy in the management of renal cell cancer. AB - Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control. PMID- 24213124 TI - Carbon Ion Radiotherapy at the Gunma University Heavy Ion Medical Center: New Facility Set-up. AB - Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first patient at Gunma University Heavy Ion Medical Center (GHMC) was initiated in March of 2010. The major specifications of the facility were determined based on the experience of clinical treatments at the National Institute of Radiological Sciences (NIRS), with the size and cost being reduced to one-third of those at NIRS. The currently indicated sites of cancer treatment at GHMC are lung, prostate, head and neck, liver, rectum, bone and soft tissue. Between March 2010 and July 2011, a total of 177 patients were treated at GHMC although a total of 100 patients was the design specification during the period in considering the optimal machine performance. In the present article, we introduce the facility set-up of GHMC, including the facility design, treatment planning systems, and clinical preparations. PMID- 24213123 TI - Nanoparticle delivery of natural products in the prevention and treatment of cancers: current status and future prospects. AB - The advent of nanotechnology has had a revolutionary impact on many aspects of 21st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called 'nanochemoprevention'. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products. PMID- 24213126 TI - The utility of proton beam therapy with concurrent chemotherapy for the treatment of esophageal cancers. AB - The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. PMID- 24213125 TI - A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG). AB - Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy), are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity. PMID- 24213127 TI - Discriminating different cancer cells using a zebrafish in vivo assay. AB - Despite the expanded understanding of tumor angiogenesis phenomenon and how it impacts cancer treatment outcomes, we have yet to develop a robust assay that can quickly, easily, and quantitatively measure tumor-induced angiogenesis. Since the zebrafish/tumor xenograft represents an emerging tool in this regard, the present study strives to capitalize on the ease, effectiveness, and the adaptability of this model to quantify tumor angiogenesis. In order to test a range of responses, we chose two different tumorigenic cell lines, the human non-small cell lung carcinoma (H1299) and the mouse lung adenocarcinoma (CL13). Non-tumorigenic 3T3 L1 cells served as negative control. The cells were grafted near to the perivitelline space of the zebrafish embryos and the angiogenic response was analyzed using whole-mount alkaline phosphatase (AP) vessel staining and fluorescence microscopy. Angiogenic activity was scored based on the length and number of the newly formed ectopic vessels and the percentage of embryos with ectopic vessels. At 2 day-post-implantation, we detected a significant increase in the length and number of ectopic vessels with H1299 cell implantation compared to CL13 cell transplantation, both are higher than 3T3-L1 control. We also observed a significantly higher percentage of embryos with ectopic vessels with H1299 and CL13 transplantation compared to the 3T3-L1 control, but this parameter is not as robust and reliable as measuring the length and number of ectopic vessels. Furthermore, the systemic exposure of zebrafish embryos to an anti angiogenesis drug (PTK 787, inhibitor of vascular endothelial growth factor receptor tyrosine kinase) inhibited tumor-induced angiogenesis, suggesting that the assay can be used to evaluate anti-angiogenic drugs. This study implicates the feasibility of using zebrafish xenotransplantation to perform quantitative measurement of the angiogenic activity of cancer cells which can be further extended to measure cancer cell metastasis. This assay represents not only the useful test for patient diagnosis, but also has the potential for evaluating anti cancer drugs treatment. PMID- 24213128 TI - Distribution of functional liver volume in hepatocellular carcinoma patients with portal vein tumor thrombus in the 1st branch and main trunk using single photon emission computed tomography-application to radiation therapy. AB - PURPOSE: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT) by exploring the relation of FLV in MV to radiation induced liver disease (RILD). METHODS AND MATERIALS: Clinical target volume (CTV) included main tumor and PVTT, and planning target volume (PTV) included CTV with a 10 mm margin. MV was defined as PTV-CTV. FLV ratio in MV was calculated as FLV in MV/MV * 100 (%). The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child-Pugh grade B) with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV * 100 (%). RESULTS: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001). Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200-300 cm3, three with CTV of 500-600 cm3, and two with CTV of 1100-1200 cm3. The destructive ratio yielded a mean value of 24.2 +/- 1.5%. CONCLUSIONS: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD. PMID- 24213129 TI - Risk of Prostate Cancer after Trans Urethral Resection of BPH: A Cohort and Nested Case-Control Study. AB - Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of inflammation in the resected material. The Pathology Department at the University Hospital of Umea (Umea, Sweden) identified BPH cases (n = 7,901) that underwent TURP between 1982 and 1997. Using these pathological specimens, we compared the incidence of PCa in the cohort to the population and calculated the standardized incidence and mortality ratios (SIR and SMR). Inflammation, the androgen receptor (AR), and p53 were evaluated in a nested case-control study of 201 cases and controls. Inflammation was graded severe or mild-moderate. In the follow-up period after TURP, cases developed prostate cancer and the controls did not. After TURP, SIR for prostate cancer increased [1.26, CI 95% (1.17-1.35)], whereas SMR decreased [0.59, CI 95% (0.47-0.73)]. Presence of inflammation at the time of TURP did not differ between cases and controls nor were there differences in p53 or AR staining. The data suggest a small increased risk of PCa after TURP and decreased PCa mortality. Inflammation at the time of TURP is not associated with PCa risk in this material. The increased PCa risk may be attributed to increased surveillance and PSA screening. PMID- 24213130 TI - Sarcoma immunotherapy. AB - Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis. PMID- 24213131 TI - Carbohydrate mimetic peptides augment carbohydrate-reactive immune responses in the absence of immune pathology. AB - Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between "tumor destruction" and "tissue damage", as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses. PMID- 24213132 TI - Transcription inhibition as a therapeutic target for cancer. AB - During tumorigenesis the transformed cells lose their normal growth control mechanisms and become dependent on oncogenes' products and pathways for survival. Treatments tailored to block the expression or function of transforming genes have shown efficacy in eliminating neoplastic cells. The mRNAs of many oncogenes, as well as regulators of other key processes such as cell proliferation, angiogenesis, and apoptosis, typically have shorter half-lives. Agents that impede mRNA synthesis are expected to selectively hinder the expression of these genes and, therefore, be detrimental to neoplastic cells that are physiologically dependent on them. In addition to exploiting the tumor cells' dependency on short lived transcripts, RNA-directed agents also take advantage of the differential sensitivity between transformed and non-transformed cells, as the cytotoxic effects of inhibiting RNA synthesis have not been seen in non-transformed cells. The abrogation of the formation of oncotranscripts provides a new concept in cancer therapeutics and numerous agents have been developed which are able to target transcription. The focus of this review is to give an overview of transcription and the different inhibitory strategies that target various aspects of the transcriptional process. PMID- 24213133 TI - Cancer genome sequencing and its implications for personalized cancer vaccines. AB - New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines. PMID- 24213134 TI - Immunohistochemical Assessment of Expression of Centromere Protein-A (CENPA) in Human Invasive Breast Cancer. AB - Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein -A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)-the 70 gene signature MammaPrint(r) and the five gene Molecular Grade Index (MGISM). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan-Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker. PMID- 24213135 TI - A novel therapeutic strategy for the treatment of glioma, combining chemical and molecular targeting of hsp90a. AB - Hsp90a's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90a was downregulated using the post-transcriptional RNAi strategy (sihsp90a) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90a, 17-AAG and concurrent sihsp90a/17-AAG (combined treatment). Both Hsp90a gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90a, 17-AAG and a combination of sihsp90a/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90a mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90a, 17-AAG and sihsp90a/17-AAG, respectively. The relationship between Hsp90a protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90a, 17-AAG and sihsp90a/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90a inhibition. Both Hsp90a and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90a protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90a protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90a mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90a in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy. PMID- 24213136 TI - Stroma-directed molecular targeted therapy in gastric cancer. AB - Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone, but also by a variety of stromal cells. Tumor stroma contains abundant extracellular matrix and several types of cells, including carcinoma-associated fibroblasts (CAFs), endothelial cells, pericytes and inflammatory cells including macrophages. In gastric cancer tissues, tumor cells express platelet-derived growth factor (PDGF)-B. Stromal cells, including CAFs, pericytes and lymphatic endothelial cells, express PDGF receptor (PDGFR)-beta. Administration of PDGFR tyrosine kinase inhibitor significantly decreases stromal reaction, lymphatic vessel area and pericyte coverage of tumor microvessels. Administration of PDGFR tyrosine kinase inhibitor in combination with cytotoxic chemotherapeutic drug(s) impairs the progressive growth and metastasis of gastric cancer. Activated stroma might serve as a novel therapeutic target in cases of gastric cancer. PMID- 24213137 TI - NF-kappaB in lung tumorigenesis. AB - The development of lung cancer in humans can be divided into three steps: initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis. PMID- 24213138 TI - Actin-towards a deeper understanding of the relationship between tissue context, cellular function and tumorigenesis. AB - It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts to control epithelial cell growth. In the breast, epithelial tumors are surrounded by an environment which lacks LN1. These findings point to actin as a potential mediator of tumor development. Here our current understanding of the roles of cytoplasmic and nuclear actin in normal and tumor cell growth is reviewed, relating these functions to cell phenotype in a tissue context. PMID- 24213139 TI - Clinical investigation of the role of interleukin-4 and interleukin-13 in the evolution of prostate cancer. AB - Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is growing evidence that the immune system, and in particular cytokines, play an important role in prostate cancer immunosurveillance and progression. Here, we have undertaken a clinical investigation of the role of two closely related cytokines, IL-4 and IL-13 in prostate cancer. In the largest series studied to date, we show that serum IL-4, but not IL-13 is significantly elevated in castrate resistant, compared to androgen sensitive disease. Notably however, serum IL-4 levels are also raised in patients with benign prostatic disease. Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. Together, our data are consistent with a dual role for IL-4 in prostate cancer development. In benign disease, our data add to the evidence that IL-4 serves a protective role. By contrast, the data support a direct role for IL-4 in the progression of prostate cancer from androgen responsive, to advanced castrate-resistant disease. PMID- 24213140 TI - Non-invasive evaluation of axillary lymph node status in breast cancer patients using shear wave elastography. AB - Less invasive procedures are currently required to examine the axillary lymph node status. Shear wave elastography with acoustic radiation force impulse provides objective and reproducible quantification of the intrinsic property of the soft tissue. In this study, we measured shear wave velocity of the axillary lymph nodes of patients with breast cancer using Virtual Touch Tissue Quantification (VTTQ). The degree of lymph node metastasis was evaluated by measuring the expression level of cytokeratin 19 (CK19) mRNA, a specific marker for breast cancer cells. The one-step nucleic acid amplification (OSNA) was used to determine the copy number of CK19 mRNA in 149 lymph node specimens of 149 primary breast cancer patients. Axillary lymph node status according to OSNA (copy number/MUl) were categorized as 0-249 copies (-), 250-5,000 copies (+), and copy number > 5,000 (++). A category (-) represents no metastasis in the axillary lymph node. There were 121 patients with OSNA-, 9 with OSNA+ and 19 with OSNA++. The average velocities according to OSNA categories were 1.64 +/- 0.42 m/second for OSNA-, 2.25 +/- 0.78 m/second for OSNA+, and 2.79 +/- 0.98 m/second for OSNA++. There were significant differences in the shear wave velocity between OSNA- and OSNA+ (P = 0.040) or OSNA++ (P < 0.001). The most optimal cutoff velocity to distinguish benign from metastasis is 1.44 m/second, as determined using the receiver operating characteristic method. The shear wave velocity measured with VTTQ could provide clinically useful information about axillary lymph node metastasis in patients with primary breast cancer. PMID- 24213141 TI - A susceptibility haplotype within the endothelial nitric oxide synthase gene influences bone mineral density in hypertensive women. AB - The influence of the coordinated effect of various single-nucleotide polymorphisms (SNPs) within the endothelial nitric oxide synthase (eNOS) gene on the risk of osteoporosis in hypertension has remained undetermined. Four pertinent SNPs of the eNOS gene, rs2070774, rs1799983, rs1800780 and rs3918181, were examined for the risk of osteoporosis in 313 hypertensive postmenopausal women in Northwest India. All the hypertensive women were verified with dual energy X-ray absorptiometry and categorized as 150 with osteoporosis and 163 without osteoporosis. The minor allele (T) of rs1799983 exerts a statistically significant risk for osteoporosis both in dominant [odds ratio (OR) 3.71, 95 % confidence interval (CI) 2.12-6.49, P < 0.001] and recessive mode (OR 5.75, 95 % CI 1.24-26.69, P = 0.036) after Bonferroni correction. Bone mineral density (BMD) values (corrected for the effects of risk variables) according to eNOS SNP genotypes revealed a significant association with rs1799983 at both the lumbar spine (P = 0.001) and femoral neck (P = 0.023). Risk association analyses revealed a susceptibility haplotype TTAG which influences the risk of osteoporosis (OR 2.02, 95 % CI 1.05-3.39, P = 0.042) in hypertension after adjusting for the effects of risk factors. Furthermore, this haplotype was significantly associated with BMD at the lumbar spine (P = 0.029) and femoral neck (P = 0.021) in a dose-dependent manner. The results suggest that possession of the TTAG haplotype of the eNOS gene may increase the risk of osteoporosis two fold in hypertensive postmenopausal women in Northwest India. PMID- 24213142 TI - A robotic MCF-7:WS8 cell proliferation assay to detect agonist and antagonist estrogenic activity. AB - Endocrine-disrupting chemicals with estrogenic activity (EA) or anti-EA (AEA) have been extensively reported to possibly have many adverse health effects. We have developed robotized assays using MCF-7:WS8 cell proliferation (or suppression) to detect EA (or AEA) of 78 test substances supplied by the Interagency Coordinating Committee on the Validation of Alternative Methods and the National Toxicology Program's Interagency Center for the Evaluation of Alternative Toxicological Methods for validation studies. We also assayed ICI 182,780, a strong estrogen antagonist. Chemicals to be assayed were initially examined for solubility and volatility to determine optimal assay conditions. For both EA and AEA determinations, a Range-Finder assay was conducted to determine the concentration range for testing, followed by a Comprehensive assay. Test substances with potentially positive results from an EA Comprehensive assay were subjected to an EA Confirmation assay that evaluated the ability of ICI 182,780 to reverse chemically induced MCF-7 cell proliferation. The AEA assays examined the ability of chemicals to decrease MCF-7 cell proliferation induced by nonsaturating concentrations of 17beta-estradiol (E2), relative to ICI or raloxifene, also a strong estrogen antagonist. To be classified as having AEA, a saturating concentration of E2 had to significantly reverse the decrease in cell proliferation produced by the test substance in nonsaturating E2. We conclude that our robotized MCF-7 EA and AEA assays have accuracy, sensitivity, and specificity values at least equivalent to validated test methods accepted by the U.S. Environmental Protection Agency and the Organisation for Economic Co operation and Development. PMID- 24213143 TI - The nature of nurture: refining the definition of the exposome. PMID- 24213144 TI - NF-kappaB signaling is increased in HD3 cells following exposure to 1,4 benzoquinone: role of reactive oxygen species and p38-MAPK. AB - In utero exposure to benzene, a known environmental contaminant, is associated with increased risk of leukemia. We have previously shown that in utero benzene exposure can alter the redox-sensitive transcription factor NF-kappaB, and we hypothesize that this is through benzene-induced reactive oxygen species (ROS) production interfering with the signaling pathway involving NF-kappaB and p38 Mitogen Activated Protein Kinase (MAPK). As benzoquinone (BQ) is one of benzene's most toxic metabolites, the objectives of this study were to determine whether ROS and p38-MAPK-mediated BQ-induced increased NF-kappaB activity. HD3 chicken erythroblast cells were transfected with an NF-kappaB luciferase-linked reporter plasmid and exposed to BQ (25 MUM) for 2-24 h. NF-kappaB activities were determined through luciferase assays; Western blotting was conducted to assess changes in protein levels in nontransfected cells; and the presence of ROS was determined via 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) flow cytometric assays. Results demonstrated that NF-kappaB activity was significantly increased following exposure to BQ for 16 and 24 h and DCFDA assays and pretreatment with antioxidants indicated that BQ-mediated ROS production was responsible for this increase. Furthermore, decreased inhibitor of kappaB-alpha (IkappaB-alpha) expression suggests that nuclear factor-kappaB (NF-kappaB) translocates into the nucleus and that p38-MAPK activation through a ROS-dependent pathway mediates BQ mediated increases in NF-kappaB activity. Future studies investigating the role of p38-MAPK in this pathway are warranted. Evaluating the effects of toxicant exposure on cell signaling pathways is vital for understanding mechanisms of xenobiotic-induced toxicity. PMID- 24213145 TI - Leukocyte telomere length and age at menopause. AB - BACKGROUND: Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. METHODS: We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women >=65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. RESULTS: For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). CONCLUSIONS: Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause. PMID- 24213146 TI - Short-term exposure to ozone and levels of exhaled nitric oxide. AB - BACKGROUND: Adverse effects of air pollution include respiratory inflammation. A few epidemiologic studies have shown elevations in the fraction of exhaled nitric oxide, a marker of airway inflammation, after exposure to traffic-related pollutants. METHODS: We examined whether short-term exposures to ozone (O3), oxides of nitrogen (NOx), or particulate matter <10 MUm (PM10) were associated with proximal and distal airway inflammation. The study included 5841 randomly selected Swedish adults from 25 to 75 years of age. Fraction of exhaled nitrogen was measured at two flow rates: 50 ml/s representing the proximal airways and 270 ml/s representing the distal airways. Air pollution data were obtained from an urban monitoring site. We applied linear regression to estimate short-term associations of O3, NOx, and PM10 with fractions of exhaled NO at 50 and 270 ml/s. RESULTS: An interquartile range increase in 120-hour average O3 levels was associated with a 5.1% (95% confidence interval = 1.7% to 8.5%) higher level of fraction of exhaled NO at 270 ml/s and 3.6% (-0.4% to 3.4%) higher level of the fraction of exhaled NO at 50 ml/s. For NOx, a small effect was seen for the 24 hour average on the fraction of exhaled NO at 270 ml/s, while for PM10 no clear effects were seen. There was a tendency for a weaker effect of ozone and a stronger effect of NOx in subjects with asthma. CONCLUSIONS: Exposure to O3 was associated with a marker of distal airway inflammation, while the association was less obvious for inflammation of the proximal airways. PMID- 24213147 TI - Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value. AB - Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy. PMID- 24213148 TI - Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas. AB - The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sezary syndrome) or disseminated nodal or visceral involvement (for non epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID- 24213149 TI - Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach. AB - The combination of oral melphalan and dexamethasone is considered standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation. However, previous trials reported different rates of response and survival, mainly because of the different proportions of high-risk patients. In the present study, including a total of 259 subjects, we treated 119 patients with full-dose melphalan and dexamethasone (dexamethasone 40 mg days 1 4), and 140 patients with advanced cardiac disease with an attenuated dexamethasone schedule (20 mg). Hematologic response rates were 76% in the full dose group and 51% in the patients receiving the attenuated schedule; the corresponding complete response rates were 31% and 12%, respectively. The median survival was 7.4 years in the full-dose group and 20 months in the attenuated dose group. Use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy were independent prognostic determinants. In relapsed/refractory subjects bortezomib combinations granted high hematologic response rates (79% and 63%, respectively), proving the most effective rescue treatment after melphalan and dexamethasone. In summary, melphalan plus dexamethasone was highly effective with minimal toxicity, confirming its central role in the treatment of AL amyloidosis. Future randomized trials will clarify whether bortezomib is best used in frontline combination with melphalan and dexamethasone or as rescue treatment. PMID- 24213150 TI - Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children. AB - Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 - 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first line therapy if horse antithymocyte globulin is not available. PMID- 24213151 TI - Differential expression of leukocyte beta2 integrin signal transduction associated genes in patients with symptomatic pulmonary embolism. AB - Whole human genome oligo microarrays were employed to systematically investigate the differential expression characteristics of associated mRNAs, which were found in the signal transduction pathway of beta2 integrins in peripheral blood mononuclear cells (PBMCs) between patients with symptomatic pulmonary embolism (PE) and controls. A total of 20 cases of PE patients and twenty gender- and age matched controls were recruited for the study. Human cDNA microarray analysis was used to detect the differences in mRNA expression between the two groups and a random variance model corrected t-test was used to analyze the statistical data. A total of 80 associated mRNAs were detected. The mRNA expression of chemokines, ligands, inside-out and outside-in signaling pathway-associated proteins were upregulated significantly in the PE group, compared with the controls. In five subunit-associated mRNAs, the mRNA expression of ITGAL, ITGAM, ITGAX and ITGB2, which encode for the subunits of alphaL, alphaM, alphaX and beta2, were upregulated in the PE group and the differences, with the exception of ITGB2, were statistically significant (P<0.05). The mRNA expression of ITGAD was downregulated; however, there was no significant difference (P>0.05). The expression of Fgr mRNA was significantly downregulated (P<0.01). Thus, in PE patients, bilateral signal transduction pathways of beta2 integrins in neutrophils and monocytes were activated, enhancing innate immunity. PMID- 24213152 TI - Nanodevice-induced conformational and functional changes in a prototypical calcium sensor protein. AB - Calcium (Ca(2+)) plays a major role in a variety of cellular processes. Fine changes in its concentration are detected by calcium sensor proteins, which adopt specific conformations to regulate their molecular targets. Here, two distinct nanodevices were probed as biocompatible carriers of Ca(2+)-sensors and the structural and functional effects of protein-nanodevice interactions were investigated. The prototypical Ca(2+)-sensor recoverin (Rec) was incubated with 20-25 nm CaF2 nanoparticles (NPs) and 70-80 nm liposomes with lipid composition similar to that found in photoreceptor cells. Circular dichroism and fluorescence spectroscopy were used to characterize changes in the protein secondary and tertiary structure and in thermal stability upon interaction with the nanodevice, both in the presence and in the absence of free Ca(2+). Variations in the hydrodynamic diameter of the complex were measured by dynamic light scattering and the residual capability of the protein to act as a Ca(2+)-sensor in the presence of NPs was estimated spectroscopically. The conformation, thermal stability and Ca(2+)-sensing capability of Rec were all significantly affected by the presence of NPs, while liposomes did not significantly perturb Rec conformation and function, allowing reversible binding. NP-bound Rec maintained an all-helical fold but showed lower thermal stability and high cooperativity of unfolding. Our analysis can be proficiently used to validate the biocompatibility of other nanodevices intended for biomedical applications involving Ca(2+) sensors. PMID- 24213153 TI - Molecular cloning and transcriptional activity of a new Petunia calreticulin gene involved in pistil transmitting tract maturation, progamic phase, and double fertilization. AB - Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca2+-binding protein in multicellular eukaryotes. As an endoplasmic reticulum-resident protein, CRT plays a key role in many cellular processes including Ca2+ storage and release, protein synthesis, and molecular chaperoning in both animals and plants. CRT has long been suggested to play a role in plant sexual reproduction. To begin to address this possibility, we cloned and characterized the full-length cDNA of a new CRT gene (PhCRT) from Petunia. The deduced amino acid sequence of PhCRT shares homology with other known plant CRTs, and phylogenetic analysis indicates that the PhCRT cDNA clone belongs to the CRT1/CRT2 subclass. Northern blot analysis and fluorescent in situ hybridization were used to assess PhCRT gene expression in different parts of the pistil before pollination, during subsequent stages of the progamic phase, and at fertilization. The highest level of PhCRT mRNA was detected in the stigma-style part of the unpollinated pistil 1 day before anthesis and during the early stage of the progamic phase, when pollen is germinated and tubes outgrow on the stigma. In the ovary, PhCRT mRNA was most abundant after pollination and reached maximum at the late stage of the progamic phase, when pollen tubes grow into the ovules and fertilization occurs. PhCRT mRNA transcripts were seen to accumulate predominantly in transmitting tract cells of maturing and receptive stigma, in germinated pollen/growing tubes, and at the micropylar region of the ovule, where the female gametophyte is located. From these results, we suggest that PhCRT gene expression is up-regulated during secretory activity of the pistil transmitting tract cells, pollen germination and outgrowth of the tubes, and then during gamete fusion and early embryogenesis. PMID- 24213155 TI - Improved plant regeneration from wheat anther and barley microspore culture using phenylacetic acid (PAA). AB - The effect of the auxin phenylacetic acid (PAA) on wheat anther and on barley anther/microspore culture was investigated. With PAA the induction response was not usually significantly different from controls but a significantly higher number of green plants were produced in wheat anther and barley microspore culture. For wheat anther culture 100 mg/L PAA was beneficial. For barley microspore culture the optimum levels were from 1 to 100 mg/L, depending on genotype. In barley anther culture there were no improvements using PAA. In wheat anther culture, 145 green plants/100 anthers were obtained with cultivar Veery'S', while the average response from twelve F1 hybrids in the breeding program was 332 green plants/100 anthers. At least 1000 green plants were obtained using isolated microspores from 100 anthers in barley cv. Igri. With cv. Bruce, regeneration occurred only when 100 mg/L PAA was used. The influence of PAA appears at the embryogenic phase of the culture system. The possible mechanisms by which PAA may improve regeneration are discussed. PMID- 24213154 TI - Evaluation of polycyclic aromatic hydrocarbons using analytical methods, toxicology, and risk assessment research: seafood safety after a petroleum spill as an example. AB - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are abundant and widespread environmental chemicals. They are produced naturally and through man-made processes, and they are common in organic media, including petroleum. Several PAHs are toxic, and a subset exhibit carcinogenic activity. PAHs represent a range of chemical structures based on two or more benzene rings and, depending on their source, can exhibit a variety of side modifications resulting from oxygenation, nitrogenation, and alkylation. OBJECTIVES: Here we discuss the increasing ability of contemporary analytical methods to distinguish not only different chemical structures among PAHs but also their concentrations in environmental media. Using seafood contamination following the Deepwater Horizon accident as an example, we identify issues that are emerging in the PAH risk assessment process because of increasing analytical sensitivity for individual PAHs, and we describe the paucity of toxicological literature for many of these compounds. DISCUSSION: PAHs, including the large variety of chemically modified or substituted PAHs, are naturally occurring and may constitute health risks if human populations are exposed to hazardous levels. However, toxicity evaluations have not kept pace with modern analytic methods and their increased ability to detect substituted PAHs. Therefore, although it is possible to measure these compounds in seafood and other media, we do not have sufficient information on the potential toxicity of these compounds to incorporate them into human health risk assessments and characterizations. CONCLUSIONS: Future research efforts should strategically attempt to fill this toxicological knowledge gap so human health risk assessments of PAHs in environmental media or food can be better determined. This is especially important in the aftermath of petroleum spills. PMID- 24213156 TI - Stably transformed herbicide resistant callus of sugarcane via microprojectile bombardment of cell suspension cultures and electroporation of protoplasts. AB - Stably transformed callus of a hybrid sugarcane cultivar (Saccharum species hybrid, CP72-1210) was achieved following high velocity microprojectile bombardment of suspension culture cells, and electroporation of protoplasts. A three-day old cell suspension culture (SC88) was bombarded with gold particles coated with pBARGUS plasmid DNA containing the beta-glucuronidase (GUS) reporter gene and the bar selectable gene that confers resistance to the herbicide basta. The pBARGUS plasmid was also electroporated into the protoplasts of another cell line (SCPP). Colonies resistant to basta were recovered from both sources. Stable integration of the bar gene in the resistant cell lines was confirmed by Southern analysis. In addition, phosphinothricin acetyltransf erase (PAT) activity was also demonstrated in the transformed cell lines. PMID- 24213157 TI - Transformation and regeneration of Brassica rapa using Agrobacterium tumefaciens. AB - Transformation and regeneration procedures for obtaining transgenic Brassica rapa ssp. oleifera plants are described. Regeneration frequencies were increasedby using silver nitrate and by adjusting the duration of exposure to 2,4-D. For transformation, Agrobacterium tumefaciens strain EHA101 containing a binary plasmid with the neomycin phosphotransferase gene (NPT II) and the b glucuronidase gene (GUS) was cocultivated with hypocotyl explants from the oilseed B. rapa cvs. Tobin and Emma. Transformed plants were obtained within three months of cocultivation. Transformation frequencies for the cultivars Tobin and Emma were 1-9%. Evidence for transformation was shown by NPT II dot blot assay, the GUS fluorometric assay, Southern analysis, and segregation of the kanamycin-resistance trait in the progeny. The transformation and regeneration procedure described here has been used routinely to transform two cultivars of B. rapa and 18 cultivars of B. napus. PMID- 24213158 TI - Agrobacterium-mediated genetic transformation of oilseed Brassica campestris: Transformation frequency is strongly influenced by the mode of shoot regeneration. AB - Protocols were developed for efficient shoot regeneration from hypocotyl and cotyledon explants of oilseed Brassica campestris (brown sarson) cv. 'Pusa Kalyani'. These were used for genetic transformation by an Agrobacterium based binary vector carrying neomycin phosphotransferase (npt) gene and beta glucuronidase (gus)-intron gene for plant cell specific expression. Transformed plants were recovered from hypocotyl explants at a frequency of 7-13%. Addition of silver nitrate markedly enhanced shoot regeneration in hypocotyl explants under non-selection conditions and was found to be an absolute requirement under selection conditions. Cotyledon explants, inspite of being more regenerative, proved to be highly refractory to transformation. Only two chimeric transformed shoots were obtained from more than 10,000 cotyledons treated with Agrobacterium. In hypocotyl explants, shoot regeneration occurred from the vascular parenchyma both with and without the intervention of callus phase. Only the shoot buds differentiating from callus tissue were positive for GUS activity. In cotyledons, shoot buds originated only directly from the vascular parenchyma, generally at a distance of about 450-625 MU from the cut surface. Such shoots were negative for GUS activity. PMID- 24213159 TI - Regeneration of shoots from embryo hypocotyls of common ash (Fraxinus excelsior). AB - The addition of thidiazuron (TDZ) to MS salts and vitamins, instead of benzylaminopurine (BAP) increased both the culture weight and the proportion of ash embryo hypocotyl explants that produced adventitious shoots. The concentration of BAP, but not that of TDZ also affected these parameters. Addition of 1-naphthalene acetic acid reduced culture performance, indolebutyric acid (IBA) was beneficial, and 2,4-dichlorophenoxyacetic acid had no effect. During both 1990 and 1991, rates of regeneration declined as the growth season progressed. Adventitious shoots, which were also obtained from hypocotyls from dried seeds, were established as proliferating shoot cultures following transfer to DKW medium with 5.0 mg l(-1) BAP, and the resulting shoots were rooted in half strength Woody Plant medium with 1.0 mg l(-1) IBA. PMID- 24213160 TI - Regeneration of plants from callus tissue of the pasture legume Centrosema brasilianum. AB - Plants were regenerated from leaf explants of Centrosema brasilianum cultured in vitro. Callus and buds were produced on Murashige and Skoog medium (MS), 0.8% agar, 0.1 mg/l NAA and 1 mg/l BAP. Regeneration of multiple shoots was achieved by transferring callus onto fresh medium containing 0.01 and 1 mg/l of NAA and BAP, respectively. Shoots formed roots upon transfer to MS with 0.01 mg/l NAA. Plantlets were succesfully transferred to soil. Leaf-derived calli of Centrosema arenarium, C. macrocarpum, C. pascuorum, C. pubescens, and C. virginianum did not produce shoots when cultured in vitro. PMID- 24213161 TI - Micropropagation of Morus laevigata Wall. from mature trees. AB - Multiple shoots were obtained from nodal explants of 10-year-old tree of Morus laevigata on Murashige and Skoog's medium supplemented with different concentrations (0.5-5.0 mg.l(-1)) of benzyladenine (BA). Nodal segments taken from in vitro proliferated shoots gave further multiple shoots when cultured on the same basal medium containing 2.5 mg.l(-1) BA. Repeated subculture resulted in rapid shoot multiplication at the average rate of 6-fold per subculture. In vitro raised shoots rooted on MS medium containing 0.1 mg. l(-1) each of 3 indolebutyric acid (ISA) and alpha-naphthaleneacetic acid (NAA). The regenerated plantlets were successfully established in soil under field conditions after a few days of indoor acclimatization. PMID- 24213162 TI - Plant regeneration from callus cultures of Piper longum L. by organogenesis. AB - Plant regeneration from callus cultures of Piper longum was achieved through organogenesis. In vitro grown shoots were used as explants for callus induction. Competent callus was initiated around the nodal ring of tissue using Murashige and Skoog medium supplemented with 1.0 mg.l(-1)alpha- naphthaleneacetic acid and 0.2 mg.l(-1) N(6)-benzyladenine. Optimum growth regulator concentrations for shoot induction and shoot elongation were found to be 0.5 mg.l(-1) indole-3 acetic acid with 1.5 mg.l(-1) benzyladenine, and 0.1 mg.l(-1) indole-3-acetic acid with 0.2 mg.l(-1) benzyladenine, respectively. Elongated shoots were rooted on half-strength Murashige and Skoog medium having 0.1 mg.l(-1) indole3-acetic acid. The rooted plants were successfully established in soil. PMID- 24213163 TI - Formation of multiple embryo-like structures from single microspores during maize anther culture. AB - In a previous study on the RFLP analysis of the maize anther culture response (Wan et al. 1992), some of the anther-derived callus Unes from hybrids H99 x Pa91 (HP) and H99 x FR16 (HF) showed the same RFLP patterns with 58 (for HP Unes) or 35 (for HF lines) RFLP markers used. Since the callus Unes with the identical RFLP pattern were initiated from individual embryo-like structures (ELSs) from the same anther culture plate, these must have originated from the same microspore. Twin embryos which apparently had originated from the same microspore were also observed. Thus in certain cases one microspore must be capable of forming more than one ELS. However, in the case of the callus Unes from a different F1 hybrid (Pa91 x FR16), no identical RFLP patterns were observed. Thus multiple ELS formation from a single microspore may be genetically controlled. Since in some cases the proportion of callus lines resulting from multiple ELS formation can be quite high (about 50% for the HP lines), estimates of gene segregation and anther culture response frequencies can be affected greatly. PMID- 24213164 TI - Callus induction and adventitious organogenesis of kenaf (Hibiscus cannabinus L.). AB - Callus production along with caulogenesis and rhizogenesis were obtained from internodal stem explants of kenaf (Hibiscus cannabinus L.) after 4 weeks in culture. Murashige and Skoog medium was used for two 4*4 matrix experiments designed to determine suitable growth regulator combinations (NAA/BAP or 2,4 D/kinetin) and concentrations (0.1, 0.3, 1.0, 3.0 mg/L). The most abundant callus production was observed at 0.3/3.0 and 1.0/3.0 mg/L 2,4-D/kinetin and at 1.0/1.0 and 3.0/1.0 mg/L NAA/BAP. Rhizogenesis was most extensive with NAA/BAP at concentrations of 0.1/3.0 and 0.3/ 3.0 mg/L. Adventitious shoots developed on both auxin/cytokinin matrixes when each concentration was at 0.3 mg/L or less. These protocols will facilitate the development of in vitro approaches to kenaf improvement and the study of certain host-pathogen interactions. PMID- 24213165 TI - Maturation of maize pollen in vitro. AB - Maturation of maize pollen was obtained in male reproductive structures cultured in vitro. Immature tassels containing microspores at the mid-uninucleate to late binucleate stage of development were excised and spikelets, anthers, and/or isolated microspores were cultured on a medium capable of supporting pollen maturation. Microspore mitosis, culminating in the production of starch-filled, trinucleate pollen capable of germination, was observed after 7-15 days, depending on the genotype and stage at which the cultures were initiated. Up to 100%, 70%, and 20% of the cultured spikelets, anthers, and isolated microspores, respectively, produced mature pollen, which germinated, however, at different frequencies (i.e., spikelets, 50-70%; anthers, 5-10%; microspores, <1%). Mature kernels were produced following fertilization with pollen from cultured spikelets and anthers. These procedures provide methods for the in vitro manipulation of a significant phase of the maize life cycle. PMID- 24213166 TI - Quantifying the local resolution of cryo-EM density maps. AB - We propose a definition of local resolution for three-dimensional electron cryo microscopy (cryo-EM) density maps that uses local sinusoidal features. Our algorithm has no free parameters and is applicable to other imaging modalities, including tomography. By evaluating the local resolution of single-particle reconstructions and subtomogram averages for four example data sets, we report variable resolution across a 4- to 40-A range. PMID- 24213168 TI - Two T-DNA's co-transformed intoBrassica napus by a doubleAgrobacterium tumefaciens infection are mainly integrated at the same locus. AB - Hypocotyl explants of threeBrassica napus varieties were infected with two nopaline typeAgrobacterium strains each carrying a distinct disarmed T-DNA containing different selectable markers. Selection was done for only one of the markers, after which the regenerated plants were screened for the presence of the second marker. High co-transformation frequencies of both T-DNA's were obtained (39%-85% of the transformants). Where the two T-DNA's were integrated linked, they were usually present in an inverted orientation relative to each other; in all of the cases observed the two right borders were adjacent. Tandem orientations occurred less frequently. The T-DNA's were mainly integrated as intact copies and deletions did not often occur. The co-transformation system described favors a genetically linked integration of the two T-DNA's (78%), although in a single transformed plant both linked and unlinked copies of both T DNA's may be present. PMID- 24213167 TI - Parallel measurement of dynamic changes in translation rates in single cells. AB - Protein concentrations are often regulated by dynamic changes in translation rates. Nevertheless, it has been challenging to directly monitor changes in translation in living cells. We have developed a reporter system to measure real time changes of translation rates in human or mouse individual cells by conjugating translation regulatory motifs to sequences encoding a nuclear targeted fluorescent protein and a controllable destabilization domain. Application of the method showed that individual cells undergo marked fluctuations in the translation rate of mRNAs whose 5' terminal oligopyrimidine (5' TOP) motif regulates the synthesis of ribosomal proteins. Furthermore, we show that small reductions in amino acid levels signal through different mTOR dependent pathways to control TOP mRNA translation, whereas larger reductions in amino acid levels control translation through eIF2A. Our study demonstrates that dynamic measurements of single-cell activities of translation regulatory motifs can be used to identify and investigate fundamental principles of translation. PMID- 24213169 TI - Identification of superior parents in a potato breeding programme. AB - An incomplete diallel cross was used to study components of genetic variation in potatoes for a range of characters after early and late harvest. The progenies were also used to evaluate five predictors of progeny performance, namely the mean seedling performance, the mid-parent value and the means of the selfed progenies, of the diploid progenies and of the test-cross progenies. For almost all characters, the general combining ability effects were predominant, although the specific combining ability effects present were greater at late than at early harvests. The seedling performance for tuber yield, number of tubers and average tuber weight did not show any relevant relationship to the field performance. The midparent value provided, in general, satisfactory predictions of the mean progeny performance obtained in the diallel, except for ware tuber yield. The selfed and the diploid progenies did not improve the prediction of progeny means compared to the mid-parent value. The predictions based on the test-crosses surpassed those of the mid-parent value, particularly for tuber yield at ware potato harvest. Methods to identify superior parents are discussed. PMID- 24213170 TI - High threonine producer mutant ofNicotiana sylvestris (Spegg. and Comes). AB - Mutagenesis and the subsequent selection of mesophyll diploid protoplasts ofNicotiana sylvestris on growth inhibitory concentrations of lysine plus threonine has led to the isolation of an LT-resistant mutant. Regeneration of this line (RLT 70) and analysis of its descendants demonstrated the dominant monogenic nuclear character of the resistance gene, further namedak-LT1. When the inhibition properties of aspartate kinase were examined in the homozygous mutant, lysine-sensitive activity could no longer be detected. In comparison, 70%-80% of the wild-type enzyme activity was usually inhibited by lysine, and the rest by threonine. Evidence for the existence of at least two AK isoenzymes was obtained by ion-exchange chromatography, where two peaks of activity could be detected: the first one to be eluted is lysine sensitive, and the second one threonine sensitive. One consequence of the altered regulation of AK in the mutant was the enhanced production of soluble threonine. Threonine accumulation was observed to occur throughout the life cycle of the mutant plant as well as in its different organs. In particular, leaves exhibited a 45-fold increment of soluble threonine, which corresponds to a 13-fold increase in total threonine: almost one-third of the total amino acids was free and proteinbound threonine. In RLT 70 seeds, 20% of the free amino acid pool was in the form of threonine (70-fold accumulation compared to the wild type), and total threonine content was increased five fold. As a general rule, the other amino acids were also more abundant in RLT 70 seeds, such that the total of amino acids present was between two to four times higher, but in contrast with the situation encountered in leaves, this was also due to a higher protein-bound amino acid content. PMID- 24213171 TI - Variable methylation and differential replication of genomic DNA in cultured carrot root expiants during growth induction as influenced by hormonal treatments. AB - The methylation and amplification pattern of genomic DNA of carrot root expiants (Daucus carota L.) undergoes transitory changes during the cultural cycle. A high degree of variation was observed as early as 36 h after the incubation of fresh expiants in the nutrient medium and, depending on the hormonal treatment significant modifications occurred during 14 days of culture. Proliferative tissue conditioned by kinetin showed an extensive reduction in DNA methylation. Changes in the DNA amplification pattern were not necessarily linked to methylation. PMID- 24213172 TI - Complementation of the amylose-free starch mutant of potato (Solanum tuberosum.) by the gene encoding granule-bound starch synthase. AB - Agrobacterium rhizogenes-mediated introduction of the wild-type allele of the gene encoding granulebound starch synthase (GBSS) into the amylose-free starch mutantamf of potato leads to restoration of GBSS activity and amylose synthesis, which demonstrates thatAmf is the structural gene for GBSS. Amylose was found in columella cells of root tips, in stomatal guard cells, tubers, and pollen, while in the control experiments using only vector DNA, these tissues remained amylose free. This confirms the fact that, in potato, GBSS is the only enzyme responsible for the presence of amylose, accumulating in all starch-containing tissues. Amylose-containing transformants showed no positive correlation between GBSS activity and amylose content, which confirms that the former is not the sole regulating factor in amylose metabolism. PMID- 24213173 TI - A linkage map ofBrassica rapa (syn.campestris) based on restriction fragment length polymorphism loci. AB - A detailed linkage map ofB. rapa (syn.campestris) was constructed based on segregation of 280 restriction fragment length polymorphism loci, detected by using 188 genomic DNA clones as probes on DNAs from a F2 population of Chinese cabbage 'MichihilF'*'Spring broccoli.' These genetic markers covered 1,850 centiMorgans (cM) and defined ten linkage groups, which equals the haploid chromosome number of this species. Extensive sequence duplication was evident by the detection of two or more segregating loci with each of 69 clones (36.7% of the total). Although some duplicated loci were randomly distributed throughout the genome, many had linkage arrangements that were conserved on different linkage groups, suggesting that large chromosome fragments were present in multiple copies. However, conservation in the linkage arrangement of duplicate loci throughout entire pairs of linkage groups was not observed. Single-copy loci were often found to be located within conserved duplicated regions, and linkage distances between some loci having conserved duplicated arrangements were substantially different between the duplicated regions. Structural rearrangements, such as insertions, deletions, and inversions or combinations of these events, seemed to be related to the alternations of map distances between duplicated loci and to the dispersal of duplicated chromosome fragments. These results suggest thatB. rapa has evolved in part by duplication of chromosomes or large chromosome fragments with subsequent structural rearrangements. PMID- 24213174 TI - Index selection with nonlinear profit function as a tool to achieve simultaneous genetic gain. AB - Simultaneous improvement of several, and often negatively correlated, traits is frequently a desired objective in forest tree breeding. A profit function that includes a combination of both linear weights and weights for the cross-products of trait combinations facilitates the construction of a linear index, with an attractive response in all traits. A detailed algorithm for finding the index coefficients is provided, along with three examples of applications in tree breeding. The index is also a powerful tool in optimizing the selection for a ratio of two traits. It is argued that a more equal progress in several traits provides a safetey net when faced with economic uncertainties. The provided algorithm eliminates the need for direct search techniques. Existence of a dual set of linear weights means that the statistical properties of the index based on nonlinear profit functions are identical to those of the classical Smith-Hazel type of index. PMID- 24213175 TI - Effective number of pollen parents in clonal seed orchards. AB - A method for quantifying mating behavior in clonal seed orchards of forest tree species is presented. It involves the estimation of effective numbers of pollen parents from seed samples collected from individual ramets in such orchards. These effective numbers are variance effective numbers for populations of male gametes that are successful in uniting with ovules to produce viable seed. Three such effective numbers are defined for clonal seed orchards:N p (a) for male gamete populations for ramets within clones,N p (b) for male gamete populations for clones, andN p (c) for male gamete populations for entire orchards. Estimators for these effective numbers and for standardized variances of allele frequencies in the male gametic populations are presented. Expressions are also given for the confidence intervals for each of the three effective numbers. Estimates of these parameters and the corresponding confidence intervals for two seed orchards are presented and interpreted. PMID- 24213176 TI - Mitochondrial genome size variation and restriction fragment length polymorphisms in threePhaseolus species. AB - Restriction patterns of mitochondrial DNA (mtDNA) from threePhaseolus species were examined to estimate their relative genome sizes and to determine the level of interspecific variability and relatedness. Three restriction endonucleases that produced relatively simple profiles were identified and used to determine the genome size of the three species. Taking into account fragment stoichiometries, the average estimates across enzymes were 456, 324, and 400 kb, respectively, forP. vulgaris, P. coccineus, andP. acutifolius. Restriction fragment length polymorphisms (RFLPs) differentiated the species when the mtDNAs were digested with seven endonucleases and hybridized with five cosmid clones covering ca. 200 kb of mtDNA sequences. Proportions of shared restriction fragments between every two species were computed as F-values and demonstrated thatP. vulgaris andP. coccineus are more related to each other than either is toP. acutifolius, and that the latter has a similar degree of relationship to the other two species. PMID- 24213177 TI - Prediction of response with overlapping generations accounting for multistage selection. AB - A generalization of Hill's equations predicting response to selection is developed that accounts for multiple stage selection in either or both sexes. The method accounts for the flow of genes for animals selected at later stages. This allows for the use of genetic gains from later stages, which explains the reduction in variance due to previous selection. Genetic gains from different selection differentials in each reproductive pathway are incorporated into the equations. The asymptotic response to a single cycle of selection is shown to agree with classical selection theory.The method is applied to a dairy progeny testing scheme representative of an artificial insemination organization in the USA. Two models were compared: (1) the first model accounted for two-stage selection of males, the first stage being based on pedigree information and the second stage on both pedigree and progeny test information; and (2) the second model assumed single-stage male selection. Selection was based on milk volume, milk fat, and milk protein yields. The predicted asymptotic rates for a single cycle of selection were overestimated by 6% and the cumulative response to continuous selection over 20 years was overestimated by 8% by assuming singlestage male selection. PMID- 24213178 TI - Isozyme analysis of progeny derived from (Allium fistulosum *Allium cepa) *Allium cepa. AB - Relatively large quantities of seed were obtained from the interspecific backcross (A. fistulosum xA. cepa) *A. cepa allowing, for the first time, an extensive study of the heritable traits exhibited by backcross progeny. Two backcross populations, BC1034 and BC1040, distinguished by differentA. fistulosum parents, were characterized for the isozyme markersIdh-1, Adh-1, andPgi-1. Statistical methods are described to calculate cell probabilities for a mixed population of F2 and BC1 progeny, using an estimate of the fraction of F2 progeny in the population derived from the isozyme data. Cell probability distributions were calculated for a mixed population with independent pairs of loci and a mixed population with nonindependent pairs of loci. The isozyme lociIdh-1 andPgi-1 appear to be linked, with a map distance estimated at 33 centimorgans (cM) in BC1034 and 42 cM in BC1040. The probability distribution model for linked loci did not account for all of the distorted segregation ratios inIdh-1 *Adh-1 orPgi 1 *Adh-1. The cytological literature does not support linkage betweenIdh-1 *Adh-1 orPgi-1 *Adh-1. The distorted segregation ratios for these pairs of loci are likely the result of genetic incompatibilities between the two species. PMID- 24213179 TI - Isolation and characterization of microprotoplasts from APM-treated suspension cells ofNicotiana plumbaginifolia. AB - Subprotoplasts with a DNA content of less than the G1 level (microprotoplasts) were isolated from micronucleated cells of transformedNicotiana plumbaginifolia ('Doba' line resistant to kanamycin) and characterized cytologically as well as by flow cytometry and Feulgen microdensitometry. Micronuclei were induced upon treatment of the suspension cells with the anti-microtubule drug amiprophos methyl (APM). Protoplasts were fractionated on a continuous iso-osmotic gradient of Percoll; this resulted in several visible bands. Flow cytometric analysis of fluorescein and nuclear DNA contents after staining with fluorescein and DAPI respectively showed that the main band contained mostly evacuolated, intact (sub)protoplasts. Microprotoplasts contained one or a few micronuclei surrounded by a thin rim of cytoplasm and an intact plasma membrane. A maximum of 40% of the microprotoplasts in the fraction just below the main band had a DNA content less than the G1 level, in other fractions this maximum was 20%. Some of these contained an amount equivalent to that of one or a few chromosomes. The application of microprotoplasts for chromosome-mediated gene transfer in plants is indicated. PMID- 24213180 TI - Extended map for the phaseolin linkage group ofPhaseolus vulgaris L. AB - The linkage relationship of 11 bean (Phaseolus vulgaris) seed proteins (including phaseolin), 9 enzyme loci, and theP locus were analyzed in backcross and F2 progenies by use of the software package "Mapmaker." The progenies were obtained by crossing the breeding line 'XR-235-1' and the cultivar 'Calima'. Allelic differences for seed protein loci were detected with SDS-PAGE and those for enzyme loci with starch gel electrophoresis and activity stains. The seed coat color of 'Calima' is a red/beige mottled pattern and that of 'XR-235-1' is white. Segregation at theP locus was followed by recording the phenotype of the BC1S1 and F3 seed. A linkage group comprising ca. 90 cM was detected with the following gene order:Est-2 - 11 -Pha - 8 - (Spe/Spg) - 24 - P - 9 - (Spa/Spv) - 16 -Spba - 22 -Mdh-1. In addition, another linkage group was detected: (Spd/Spf/Sph) - 5 Spca. Therefore, the seed proteins appear to be organized in clusters in the bean genome. PMID- 24213181 TI - Chromosomal location of seed storage protein genes in the genome ofDasypyrum villosum (L.) Candargy. AB - Genes coding for glutenin-like subunits and for several prolamin subunits with electrophoretic mobilities (lactate-PAGE) corresponding to those of omega- and gamma-gliadins of wheat were located inDasypyrum villosum chromosome1V. Genes controlling four gliadinlike subunits with electrophoretic mobilities corresponding to those of alpha- and gamma-gliadins were located on the short arm of chromosome6V and on the long arm of chromosome4V. N-terminal amino acid sequences of these four components were also determined and homology with alpha type gliadins was demonstrated. The presence of genes coding for glutenin- and gliadin-like subunits on chromosomes1V and6V demonstrates homoeology between theD. villosum chromosomes1V and6V and the chromosomes of homoeologous groups 1 and 6 in wheat. It is likely that the additional locusGli-V3 on chromosome4V originated by translocation from theGli-V2 locus. PMID- 24213182 TI - Selection for local adaptation in a plant breeding programme. AB - Regressions of yields of cultivars upon means of sets of cultivars over diverse environments are often used as measures of stability/adaptability. Prolonged selection for performance in environments of high yield potential has generally led to unconscious selection for high regressions. If adaptation to poor environments is required (as it often is in Third World agriculture), common sense suggests that low regressions could be exploited for the purpose. Simulations show that systematic selection in the poor environment is required, not merely trials of potential cultivars after selection in a good environment. In effect, systematic exploitation of a GE interactions effect is proposed. The effects are large enough to reduce correlated responses in different environments to zero. Orderly experimental studies are needed but not available. What information there is does not disagree with the theory developed here. PMID- 24213183 TI - Simulation of genetic control. Homozygous-viable pericentric inversions in field female killing systems. AB - The GENCON simulation program GC5 is designed to simulate genetic population control using field-female killing (FK) systems carying pericentric inversions in addition to Y-linked translocations and deleterious mutations. Homozygous-viable pericentric inversions are included on the same chromosomes as the deleterious mutations, in repulsion to the Y-linked translocation. Released males transmit the inversions and mutations to their daughters and the translocation to their sons. Daughters are semisterile regardless of the type of male they mate with, because products of crossing-over within the inversions carry inviable duplications and deficiencies. Compared to present FK systems, inversion containing strains give higher levels of genetic death, with both faster initial suppression and greater persistence of genetic death from field-reared descendants if releases are interrupted. At low release rates, both types of FK system are more effective than sterile males. PMID- 24213184 TI - Assessment of a method for cultivar selection based on regional trial data. AB - In this study a method for analyzing regional trial data is investigated for its effectiveness in cultivar selection. The method is a synthesis of three procedures: (1) regression analysis for genotype * environment (GE) interaction, and subsequent cluster analysis for grouping cultivars for similarity of response; (2) superiority measure analysis of cultivar performance based on the distance mean square between the test cultivar and the maximum response; (3) type 4 stability analysis for three-way classification data (cultivar * location * year), to measure a cultivar's stability. Each of these three procedures is aimed at different aspects of the selection problem: the first obtains an overview of the types of cultivar response; the second measures a cultivar's general adaptability within the region; the third assesses a cultivar's ability to withstand unpredictable variation, namely that caused by year effects. Four sets of published data, each originally analyzed by a univariate or a multivariate approach, were used as examples. The results suggest that the present method provides direct and useful information for selection purposes. The superiority measure, which is the core of the method, can be used even if the data do not fit the linear model for GE interaction. Plotting the data with a fixed standard represented by the maximum response provides a simple visual tool for identifying environments where a cultivar performs well. PMID- 24213185 TI - Erratum. PMID- 24213186 TI - Significant differences in drug lag in clinical development among various strategies used for regulatory submissions in Japan. AB - Although the number of global clinical trials (GCTs) conducted in multiple countries including Japan has increased recently, it is not clear how much these GCTs help in reducing the lag in drug development (LDD: difference between the submission dates for new drug applications (NDAs) in the United States and Japan). We examined the effects of various clinical development strategies on LDD because the development period depends on what types of clinical trials were conducted for the Japanese NDA. Although various drug development strategies are available, deciding early on an appropriate strategy is a key to minimizing the LDD in Japan. The inclusion of GCTs in the clinical development strategy is also important; simultaneously, the smaller sample size of the Japanese population should be taken into consideration. Furthermore, reinforcement of Japan's capability to lead drug development may also be important in providing innovative drugs to Japanese patients without any significant LDD. PMID- 24213187 TI - Electrochemical ammonia production on molybdenum nitride nanoclusters. AB - Theoretical investigations of electrochemical production of ammonia at ambient temperature and pressure on nitrogen covered molybdenum nanoparticles are presented. Density functional theory calculations are used in combination with the computational hydrogen electrode approach to calculate the free energy profile for electrochemical protonation of N2 and N adatoms on cuboctahedral Mo13 nanoparticles. Pathways for electrochemical ammonia production via direct protonation of N adatoms and N2 admolecules with an onset potential as low as 0.5 V and generally lower than -0.8 V on both a nitrogen covered or a clean Mo nanoparticle. Calculations presented here show that nitrogen dissociation at either nitrogen vacancies on a nitrogen covered molybdenum particle or at a clean molybdenum particle is unlikely to occur under ambient conditions due to very high activation barriers of 1.8 eV. The calculations suggest that the nitrogen will be favored at the surface compared to hydrogen even at potentials of -0.8 V and the Faradaic losses due to HER should be low. PMID- 24213188 TI - First report on Cryptococcus neoformans in pigeon excreta from public and residential locations in the metropolitan area of Cuiaba, State of Mato Grosso, Brazil. AB - Cryptococcosis is a severe systemic mycosis caused by two species of Cryptococcus that affect humans and animals: C. neoformans and C. gattii. Cosmopolitan and emergent, the mycosis results from the interaction between a susceptible host and the environment. The occurrence of C. neoformans was evaluated in 122 samples of dried pigeon excreta collected in 49 locations in the City of Cuiaba, State of Mato Grosso, Brazil, including public squares (n = 5), churches (n = 4), educational institutions (n = 3), health units (n = 8), open areas covered with asbestos (n = 4), residences (n = 23), factory (n = 1) and a prison (n = 1). Samples collected from July to December of 2010 were seeded on Niger seed agar (NSA). Dark brown colonies were identified by urease test, carbon source assimilation tests and canavanine-glycine-bromothymol blue medium. Polymerase chain reaction primer pairs specific for C. neoformans were also used for identification. Cryptococcus neoformans associated to pigeon excreta was isolated from eight (6.6%) samples corresponding to six (12.2%) locations. Cryptococcus neoformans was isolated from urban areas, predominantly in residences, constituting a risk of acquiring the disease by immunocompromised and immunocompetent individuals. PMID- 24213189 TI - Distribution of dermatophytes from soils of urban and rural areas of cities of Paraiba State, Brazil. AB - The dermatophytes, keratinophilic fungi, represent important microorganisms of the soil microbiota, where there are cosmopolitan species and others with restricted geographic distribution. The aim of this study was to broaden the knowledge about the presence of dermatophytes in soils of urban (empty lots, schools, slums, squares, beaches and homes) and rural areas and about the evolution of their prevalence in soils of varying pH in cities of the four mesoregions of Paraiba State, Brazil. Soil samples were collected from 31 cities of Paraiba State. Of 212 samples, 62% showed fungal growth, particularly those from the Mata Paraibana mesoregion (43.5%), which has a tropical climate, hot and humid. Soil pH varied from 4.65 to 9.06, with 71% of the growth of dermatophytes occurring at alkaline pH (7.02 - 9.06) (rho = 0.000). Of 131 strains isolated, 57.3% were geophilic species, particularly Trichophyton terrestre (31.3%) and Mycrosporum gypseum (21.4%). M. nanum and T. ajelloi were isolated for the first time in Paraiba State. The zoophilic species identified were T. mentagrophytes var. mentagrophytes (31.3 %) and T. verrucosum (7.6 %), and T. tonsurans was isolated as an anthropophilic species. The soils of urban areas including empty lots, schools, slums and squares of cities in the mesoregions of Paraiba State were found to be the most suitable reservoirs for almost all dermatophytes; their growth may have been influenced by environmental factors, soils with residues of human and/or animal keratin and alkaline pH. PMID- 24213190 TI - Molecular typing of Candida albicans isolates from hospitalized patients. AB - INTRODUCTION: The majority of nosocomial fungal infections are caused by Candida spp. where C. albicans is the species most commonly identified. Molecular methods are important tools for assessing the origin of the yeasts isolated in hospitals. METHODS: This is a study on the genetic profiles of 39 nosocomial clinical isolates of C. albicans using two typing methods: random amplified polymorphic DNA (RAPD) and microsatellite, two different primers for each technique were used. RESULTS: RAPD provided 10 and 11 different profiles with values for S(AB) of 0.84 +/- 0.126 and 0.88 +/- 0.08 for primers M2 and P4, respectively. Microsatellite using two markers, CDC3 and HIS3, allowed the observation of six and seven different alleles, respectively, with combined discriminatory power of 0.91. CONCLUSIONS: Although genetic variability is clear, it was possible to identify high similarity, suggesting a common origin for at least a part of isolates. It is important to emphasize that common origin was proven from yeasts isolated from colonization (urine, catheter or endotracheal secretions) and blood culture from the same patient, indicating that the candidemia must have started from a site of colonization. The combination of RAPD and microsatellite provides a quick and efficient analysis for investigation of similarity among nosocomial isolates of C. albicans. PMID- 24213191 TI - Applicability of kDNA-PCR for routine diagnosis of American tegumentary leishmaniasis in a tertiary reference hospital. AB - This study evaluated the applicability of kDNA-PCR as a prospective routine diagnosis method for American tegumentary leishmaniasis (ATL) in patients from the Instituto de Infectologia Emilio Ribas (IIER), a reference center for infectious diseases in Sao Paulo - SP, Brazil. The kDNA-PCR method detected Leishmania DNA in 87.5% (112/128) of the clinically suspected ATL patients, while the traditional methods demonstrated the following percentages of positivity: 62.8% (49/78) for the Montenegro skin test, 61.8% (47/76) for direct investigation, and 19.3% (22/114) for in vitro culture. The molecular method was able to confirm the disease in samples considered negative or inconclusive by traditional laboratory methods, contributing to the final clinical diagnosis and therapy of ATL in this hospital. Thus, we strongly recommend the inclusion of kDNA-PCR amplification as an alternative diagnostic method for ATL, suggesting a new algorithm routine to be followed to help the diagnosis and treatment of ATL in IIER. PMID- 24213192 TI - Comparison of six commercially-available DNA polymerases for direct PCR. AB - The use of a "direct PCR" DNA polymerase enables PCR amplification without any prior DNA purification from blood samples due to the enzyme's resistance to inhibitors present in blood components. Such DNA polymerases are now commercially available. We compared the PCR performance of six direct PCR-type DNA polymerases (KOD FX, Mighty Amp, Hemo KlenTaq, Phusion Blood II, KAPA Blood, and BIOTAQ) in dried blood eluted from a filter paper with TE buffer. GoTaq Flexi was used as a standard DNA polymerase. PCR performance was evaluated by a nested PCR technique for detecting Plasmodium falciparum genomic DNA in the presence of the blood components. Although all six DNA polymerases showed resistance to blood components compared to the standard Taq polymerase, the KOD FX and BIOTAQ DNA polymerases were resistant to inhibitory blood components at concentrations of 40%, and their PCR performance was superior to that of other DNA polymerases. When the reaction mixture contained a mild detergent, only KOD FX DNA polymerase retained the original amount of amplified product. These results indicate that KOD FX DNA polymerase is the most resistant to inhibitory blood components and/or detergents. Thus, KOD FX DNA polymerase could be useful in serological studies to simultaneously detect antibodies and DNA in eluents for antibodies. KOD FX DNA polymerase is thus not limited to use in detecting malaria parasites, but could also be employed to detect other blood-borne pathogens. PMID- 24213193 TI - Phlebotomine sandflies in rural locations in the State of Parana, southern Brazil. AB - This study reports the fauna and frequency of sandflies in domestic animal shelters, residences and other ecotopes in rural areas of the municipality of Bandeirantes, Parana State. Sandflies were collected twice in eight rural villages by using Falcon traps from 8pm to 6am in 2008. In these localities 4,790 sandflies were collected, which were represented by ten sandfly species, prevailing of Nyssomyia neivai and Nyssomyia whitmani species. It was observed that animal shelters are the domestic ecotopes where there is the greatest frequency of these insects. The localities where the collections were made had the environmental characteristics that allow the persistence of transmission of parasites from the American tegumentary leishmaniasis. Although the fauna and the behavior of sandflies species are similar in different localities, the method of controlling these insects should be adjusted to the environmental characteristics of each one of the most diverse endemic areas of American tegumentary leishmaniasis in the municipalities of Parana State. PMID- 24213194 TI - Potentially pathogenic free-living amoebae in some flood-affected areas during 2011 Chiang Mai flood. AB - The survey was carried out to investigate the presence of potentially pathogenic free-living amoebae (FLA) during flood in Chiang Mai, Thailand in 2011. From different crisis flood areas, seven water samples were collected and tested for the presence of amoebae using culture and molecular methods. By monoxenic culture, FLA were detected from all samples at 37 degrees C incubation. The FLA growing at 37 degrees C were morphologically identified as Acanthamoeba spp., Naegleria spp. and some unidentified amoebae. Only three samples (42.8%), defined as thermotolerant FLA, continued to grow at 42 degrees C. By molecular methods, two non-thermotolerant FlA were shown to have 99% identity to Acanthamoeba sp. and 98% identity to Hartmannella vermiformis while the two thermotolerant FLA were identified as Echinamoeba exundans (100% identity) and Hartmannella sp. (99% identity). This first report of the occurrence of FLA in water during the flood disaster will provide information to the public to be aware of potentially pathogenic FLA. PMID- 24213195 TI - Smqnr variants in clinical isolates of Stenotrophomonas maltophilia in Brazil. AB - Stenotrophomonas maltophilia contains a novel chromosomally-encoded qnr gene named Smqnr that contributes to low intrinsic resistance to quinolone. We described Smqnr in 13 clinical isolates of S. maltophilia from two Brazilian hospitals, over a 2-year period. The strains were identified by API 20 NE (bioMerieux, France). Susceptibility by microdilution method to trimetroprim/sulfamethoxazole, ciprofloxacin, levofloxacin, minocycline, ceftazidime, chloramphenicol and ticarcillin/clavulanate was performed according to CLSI. PCR detection of Smqnr gene was carried out. The sequence of Smqnr was compared with those deposited in GenBank. Pulsed-field gel electrophoresis (PFGE) of all strains was performed. Thirteen Smqnr positives isolates were sequenced and three novel variants of Smqnr were identified. All 13 Smqnr isolates had distinguishable patterns by PFGE. This is the first report of Smqnr in S. maltophilia isolated in Brazil. PMID- 24213196 TI - Ovicidal effect of Piperaceae species on Biomphalaria glabrata, Schistosoma mansoni host. AB - Schistosomiasis is a neglected disease with public health importance in tropical and subtropical regions. An alternative to the disease control is the use of molluscicides to eliminate or reduce the intermediate host snail population causing a reduction of transmission in endemic regions. In this study nine extracts from eight Piperaceae species were evaluated against Biomphalaria glabrata embryos at blastula stage. The extracts were evaluated in concentrations ranging from 100 to 10 mg/L. Piper crassinervium and Piper tuberculatum extracts were the most active (100% of mortality at 20 mg/L and 30 mg/L respectively). PMID- 24213197 TI - Case study of a patient with HIV-AIDS and visceral leishmaniasis co-infection in multiple episodes. AB - Report of a 45-year-old male farmer, a resident in the forest zone of Pernambuco, who was diagnosed with human immunodeficiency virus (HIV) in 1999 and treated using antiretroviral (ARV) drugs. In 2005, the first episode of visceral leishmaniasis (VL), as assessed by parasitological diagnosis of bone marrow aspirate, was recorded. When admitted to the hospital, the patient presented fever, hepatosplenomegaly, weight loss, and diarrhea. Since then, six additional episodes of VL occurred, with a frequency rate of one per year (2005-2012, except in 2008). In 2011, the patient presented a disseminated skin lesion caused by the amastigotes of Leishmania, as identified by histopathological assessment of skin biopsy samples. In 2005, he was treated with N-methyl-glucamine-antimony and amphotericin B deoxycholate. However, since 2006 because of a reported toxicity, the drug of choice was liposomal amphotericin B. As recommended by the Ministry of Health, this report emphasizes the need for HIV patients living in VL endemic areas to include this parasitosis in their follow-up protocol, particularly after the first infection of VL. PMID- 24213198 TI - Usefulness of kDNA PCR in the diagnosis of visceral leishmaniasis reactivation in co-infected patients. AB - It is important to develop new methods for diagnosing relapses in the co infection of visceral leishmaniasis (VL) and HIV to enable earlier detection using less invasive methods. We report a case of a co-infected patient who had relapses after VL treatment, where the qualitative kDNA PCR showed a good performance. The kDNA PCR seems to be a useful tool for diagnosing VL and may be a good marker for predicting VL relapses after treatment of co-infected patients with clinical symptoms of the disease. PMID- 24213199 TI - Differential diagnosis of respiratory viruses by using real time RT-PCR methodology. PMID- 24213200 TI - High prevalence of hepatitis A antibodies among recyclable waste pickers, Central Brazil. PMID- 24213201 TI - Analogies in medicine: violin strings adhesions. PMID- 24213202 TI - A long wavelength hydrophobic probe for intracellular lipid droplets. AB - A highly stable, long wavelength polarity sensitive probe, 8-nitrophenyl-3,5 dipiperidine-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (NPBDP), was developed for living cell imaging of intracellular lipid droplets by fluorescence microscopy. PMID- 24213204 TI - On earthquake prediction in Japan. AB - Japan's National Project for Earthquake Prediction has been conducted since 1965 without success. An earthquake prediction should be a short-term prediction based on observable physical phenomena or precursors. The main reason of no success is the failure to capture precursors. Most of the financial resources and manpower of the National Project have been devoted to strengthening the seismographs networks, which are not generally effective for detecting precursors since many of precursors are non-seismic. The precursor research has never been supported appropriately because the project has always been run by a group of seismologists who, in the present author's view, are mainly interested in securing funds for seismology - on pretense of prediction. After the 1995 Kobe disaster, the project decided to give up short-term prediction and this decision has been further fortified by the 2011 M9 Tohoku Mega-quake. On top of the National Project, there are other government projects, not formally but vaguely related to earthquake prediction, that consume many orders of magnitude more funds. They are also un interested in short-term prediction. Financially, they are giants and the National Project is a dwarf. Thus, in Japan now, there is practically no support for short-term prediction research. Recently, however, substantial progress has been made in real short-term prediction by scientists of diverse disciplines. Some promising signs are also arising even from cooperation with private sectors. PMID- 24213203 TI - Chondrosarcomas of the head and neck. AB - Chondrosarcoma represents approximately 11% of all primary malignant bone tumors. It is the second most common sarcoma arising in bone after osteosarcoma. Chondrosarcomas of the head and neck are rare and may involve the sinonasal tract, jaws, larynx or skull base. Depending on the anatomical location, the tumor can produce a variety of symptoms. Computed tomography and magnetic resonance imaging are the preferred imaging modalities. The histology of conventional chondrosarcoma is relatively straightforward; major challenges are the distinction between grade I chondrosarcomas and chondromas, and the differential diagnosis with chondroblastic osteosarcoma and chondroid chordoma. Surgery alone or followed by adjuvant radiotherapy is the treatment of choice. Radiotherapy alone has also been reported to be effective and can be considered if mutilating radical surgery is the only curative alternative. The 5-year survival for chondrosarcoma reaches 80%; distant metastases and/or local recurrences significantly worsen prognosis. The present review aims to summarize the current state of information about the biology, diagnosis and management of these rare tumors. PMID- 24213205 TI - Wireless-electrodeless quartz-crystal-microbalance biosensors for studying interactions among biomolecules: a review. AB - The mass sensitivity of quartz-crystal microbalance (QCM) was drastically improved by removing electrodes and wires attached on the quartz surfaces. Instead of wire connections, intended vibrations of quartz oscillators were excited and detected by antennas through electromagnetic waves. This noncontacting measurement is the key for ultrahigh-sensitive detection of proteins in liquids as well as quantitative measurements. This review shows the principle of wireless QCMs, their applications to studying interactions among biomolecules and aggregation reactions of amyloid beta peptides, and the next generation MEMS QCM, the resonance acoustic microbalance with naked embedded quartz (RAMNE-Q). PMID- 24213206 TI - Strong binding and shrinkage of single and double (K) nuclear systems (K(-)pp, K( )ppn, K(-)K(-)p and K(-)K(-)pp) predicted by Faddeev-Yakubovsky calculations. AB - Non-relativistic Faddeev and Faddeev-Yakubovsky calculations were made for K( )pp, K(-)ppn, K(-)K(-)p and K(-)K(-)pp kaonic nuclear clusters, where the quasi bound states were treated as bound states by employing real separable potential models for the K(-)-K(-) and the K(-)-nucleon interactions as well as for the nucleon-nucleon interaction. The binding energies and spatial shrinkages of these states, obtained for various values of the K interaction, were found to increase rapidly with the K interaction strength. Their behaviors are shown in a reference diagram, where possible changes by varying the K interaction in the dense nuclear medium are given. Using the Lambda(1405) ansatz with a PDG mass of 1405 MeV/c(2) for K(-)p, the following ground-state binding energies together with the wave functions were obtained: 51.5 MeV (K(-)pp), 69 MeV (K(-)ppn), 30.4 MeV (K(-)K( )p) and 93 MeV (K(-)K(-)pp), which are in good agreement with previous results of variational calculation based on the Akaishi-Yamazaki coupled-channel potential. The K(-)K(-)pp state has a significantly increased density where the two nucleons are located very close to each other, in spite of the inner NN repulsion. Relativistic corrections on the calculated non-relativistic results indicate substantial lowering of the bound-state masses, especially of K(-)K(-)pp, toward the kaon condensation regime. The fact that the recently observed binding energy of K(-)pp is much larger (by a factor of 2) than the originally predicted one may infer an enhancement of the K interaction in dense nuclei by about 25% possibly due to chiral symmetry restoration. In this respect some qualitative accounts are given based on "clearing QCD vacuum" model of Brown, Kubodera and Rho. PMID- 24213207 TI - On the recent seismic activity in North-Eastern Aegean Sea including the M(w)5.8 earthquake on 8 January 2013. AB - In the last week of November 2012, we announced that a strong electrotelluric disturbance, which we judged to be a Seismic Electric Signal (SES) activity, was recorded at station Assiros located in Northern Greece. This disturbance was actually followed by an Mw5.8 earthquake on 8 January 2013 in North-Eastern Aegean Sea. Here we show that, by analyzing this SES activity and employing the natural time analysis of subsequent seismicity, we estimated the epicentral location, magnitude and occurrence time which are reasonably compatible with those of the Mw5.8 event. PMID- 24213208 TI - On the relation between dry matter and volume of bacteria. AB - Dry matter and volumes of 337 individual bacterial cells with volumes in the range 0.01-7MUm(3) from different origins were measured. An allometric relation was established between dry matter and volume, such that smaller bacteria tended to have a higher dry matter to volume ratio than larger bacteria. The results are compared to results from similar work on algae. The implications for the use of conversion factors are discussed. PMID- 24213209 TI - The relationship between cell size and viability of soil bacteria. AB - The number of bacterial cells in soil that form colonies on nutrient agar represent a small fraction of the direct microscopic counts (DMC). The colony forming cells have larger cell dimensions than the very small ("dwarf") cells which represent the majority of the DMC. This may indicate that the dwarf cells are species unable to form visible colonies on agar, or that they swell to normal dimensions when growing. Indigenous bacterial cells were separated from soil by density gradient centrifugation and fractionated according to diameter by filtration through polycarbonate filters. Each filtrate was studied with respect to DMC, cell dimensions, colony-forming cells (visible colonies and microcolonies), and cell dimensions during growth on the agar. The calculated average percent viability was only 0.2% for cells with diameters below 0.4MUm, about 10% for cells with diameters between 0.4 and 0.6MUm, and 30-40% for cells with diameters above 0.6MUm. Only 10-20% of the viable cells with diameters <0.4MUm increased their diameter to >0.4MUm prior to growth. Thus, size change during starvation and growth cycles did not explain the high numbers of dwarf cells observed by microscopy. The results show that despite the relatively low number of colony-forming bacteria in soil, the species that form colonies may be fairly representative for the medium size and large cells, which constitute a major part of the bacterial biovolume. Thus plate counting could be a useful method to count and isolate the bacteria accounting for much of the biovolume in soil. The origin of the dwarf cells is still unclear, but the low number of small cells that increased in size seems to indicate that the majority of these bacterial cells are not small forms of ordinary sized bacteria. PMID- 24213210 TI - Divider size and the cell cycle after prolonged starvation ofTetrahymena corlissi. AB - Cell growth and division of the ciliateTetrahymena corlissi were examined upon refeeding after prolonged starvation of up to 12 days. Division did not automatically occur when a certain critical cell size was reached. Rather, it varied both with the nutritional history of the cell and the nutrient conditions in which the cell was growing. Upon refeeding, cells starved for 12 days divided at a smaller size and later than cells starved for 6 days. Cells refed at high density took longer to begin division than cells refed at low density. The results are discussed with respect to the "relative starvation" and "critical constituent" models of the cell cycle and in terms of the polymorphic life cycle ofTetrahymena species. PMID- 24213211 TI - Bacterial communities associated with "Pompei worms" from the East Pacific rise hydrothermal vents: SEM, TEM observations. AB - A morphological study of bacteria associated with the "Pompei worm,"Alvinella pompejana, collected from East Pacific rise hydrothermal vents, revealed four types of epidermal associations on the dorsal part of the animals: various single cells distributed on the animal tegument; clump-like associations located in the intertegumentary spaces; and filamentous bacteria associated with epidermal expansions, or inserted on the posterior parapodia. The bacterial morphologies were illustrated by SEM and TEM pictures and compared to bacteria previously described. The functional significance of these associations is discussed. PMID- 24213212 TI - A model for acid and alkaline phosphatase activity in a small pond. AB - Acid and alkaline phosphatase activity were determined in a small pond over a period of 24 months (64 samples). Activity of each phosphatase enzyme was positively correlated with chlorophyll concentration, viable bacterial count, total phosphate concentration, inorganic phosphate concentration, and temperature. Multiple regression analysis was used to formulate equations that described phosphatase activity in terms of these physical, chemical, and biotic factors. Corrected coefficients of determination were calculated, and the highest values were obtained when all parameters were included in the equation (r (2)=0.776 and 0.659 for alkaline and acid phosphatase activity, respectively). However, there was little improvement in ther (2) value obtained when only chlorophyll was used in the equation (r (2)=0.654 and 0.624, respectively). Samples were then taken over a further 12 months (25 samples), and observed activity was compared with the activity predicted by application of the previously derived equations. For alkaline phosphatase, the best fit between observed and expected activity was seen with the equation containing all parameters, but for acid phosphatase the best fit was seen with the equation containing only chlorophyll and temperature as the determinants. In both cases there was a good fit between observed and expected data using the equation containing chlorophyll as the sole determinant. From this we have concluded that phytoplankton were the chief producers of phosphatase activity in this pond, although the influence of physical and chemical factors on enzyme activity could not be ignored. PMID- 24213213 TI - Characterization of aerobic, facultative anaerobic, and anaerobic bacteria in an acidogenic phase reactor and their metabolite formation. AB - Fifty-two aerobic and facultative anaerobic and 57 anaerobic bacterial isolates were obtained from an acidogenic phase digestion system. These isolates were characterized and the similarities between the different strains were calculated using Sokal and Michener's similarity coefficient. The aerobic and facultative anaerobic strains clustered in two major groups with the strains of the first main group being gram-negative fermentative rods, representing the generaKlebsiella, Enterobacter, Escherichia andAeromonas. Isolates of the second group were gram-positive streptococci similar toStreptococcus lactis. The strict anaerobic isolates also clustered into two main groups with strains of cluster A being identified as members of the genusFusobacterium while strains in cluster B were members of the genusBacteroides. Hypothetical mean organisms were calculated for each cluster and used in further culture studies. The major products of the continuously fed acidogenic phase reactor were ethanol and acetic, propionic, and butyric acids. In batch cultures, ethanol, acetic acid, diacetyl, and 2,3 butanediol were formed by the strains as major products both under aerobic and anaerobic conditions. The ability of the aerobic and facultative anaerobic strains to be metabolically active under anaerobic conditions indicates a prominent role in acidogenic reactors. PMID- 24213214 TI - Phase transformations in nanograin materials under high pressure and plastic shear: nanoscale mechanisms. AB - There are two main challenges in the discovery of new high pressure phases (HPPs) and transforming this discovery into technologies: finding conditions to synthesize new HPPs and finding ways to reduce the phase transformation (PT) pressure to an economically reasonable level. Based on the results of pressure shear experiments in the rotational diamond anvil cell (RDAC), superposition of plastic shear on high pressure is a promising way to resolve these problems. However, physical mechanisms behind these phenomena are not yet understood. Here, we elucidate generic mechanisms of coupled nucleation and evolution of dislocation and HPP structures in the nanograin material under pressure and shear utilizing the developed advanced phase field approach (PFA). Dislocations are generated at the grain boundaries and are densely piled up near them, creating a strong concentrator of the stress tensor. Averaged shear stress is essentially larger in the nanograin material due to grain boundary strengthening. This leads to the increase in the local thermodynamic driving force for PT, which allows one to significantly reduce the applied pressure. For all cases, the applied pressure is 3-20 times lower than the PT pressure and 2-12.5 times smaller than the phase equilibrium pressure. Interaction between nuclei leads sometimes to their coalescence and growth of the HPP away from stress concentrators. Plasticity plays a dual role: in addition to creating stress concentrators, it may relax stresses at other concentrators, thus competing with PT. Some ways to optimize the loading parameters have been found that lead to methods for controlling PT. Since such a local stress tensor with high shear stress component cannot be created without plastic deformations, this may lead to new transformation paths and phases, which are hidden during pressure induced PTs. PMID- 24213215 TI - The association between poor antiretroviral adherence and unsafe sex: differences by gender and sexual orientation and implications for scale-up of treatment as prevention. AB - Non-adherence to safer sex and non-adherence to ART can each have adverse health consequences for HIV-infected individuals and their sex partners, but little is known about the association of these behaviors with each other. This "dual risk" has potential negative public health consequences since non-adherence can lead to the development of resistant virus that can then be transmitted to sex partners. Among participants in the Multi-site Adherence Collaboration in HIV we examined, at study baseline, the association between the frequency of unprotected sex (assessed by self-report) and ART adherence (assessed by Medication Event Monitoring System, Aardex) among the sexually active participants in the five studies (N = 459) that collected sexual risk behavior. The bivariate association between sexual risk behaviors and ART adherence was assessed by Pearson correlations; subsequently regression analyses were used to evaluate the role of demographic characteristics, depression and substance use in explaining the "dual risk" outcome (sexual risk and non-adherence). Among participants who had been sexually active, more unprotected anal/vaginal sex was weakly associated with poorer ART adherence (r = -0.12, p = 0.01 for the overall sample). Further analysis showed this association was driven by the heterosexual men in the sample (r = -0.29, p < 0.001), and was significant only for this group, and not for gay/bisexual men or for women (heterosexual and homosexual). Neither substance use nor depression accounted for the association between sexual risk and ART adherence. HIV-infected heterosexual men who are having difficulty adhering to ART are also more likely to engage in risky sexual behaviors and therefore may benefit from counseling about these risk behaviors. We must identify procedures to screen for these risk behaviors and develop interventions, appropriately tailored to specific populations and identified risk factors, that can be integrated into routine clinical care for people living with HIV. This will become increasingly important in the context of wider access to treatment globally, including new recommendations for ART initiation earlier in a patients' disease course (e.g., "Test and Treat" paradigms). PMID- 24213216 TI - Once-weekly teriparatide reduces the risk of vertebral fracture in patients with various fracture risks: subgroup analysis of the Teriparatide Once-Weekly Efficacy Research (TOWER) trial. AB - Once-weekly teriparatide (human parathyroid hormone [1-34]) (56.5 MUg for 72 weeks) injections provided a vertebral fracture risk reduction in Japanese osteoporotic patients evaluated in the Teriparatide Once-Weekly Efficacy Research (TOWER) trial. Using data from the TOWER trial, a subgroup analysis was performed to study the efficacy of once-weekly teriparatide for a variety of baseline clinical risk factors in placebo (n = 281) and teriparatide (n = 261) groups. Significant fracture risk reductions were observed in the subgroups of individuals aged <75 years [relative risk (RR) 0.06, p = 0.007] and >=75 years (RR 0.32, p = 0.015). A significant risk reduction was observed among patients with prevalent vertebral fracture in the subgroup with 1 (RR 0.08, p = 0.015) or >=2 (RR 0.29, p = 0.009) prevalent vertebral fractures, and in those with grade 3 deformity (RR 0.26, p = 0.003). Significant risk reduction was observed in the subgroup with lumbar bone mineral density (BMD) < -2.5 SD (RR 0.25, p = 0.035). In the teriparatide group, no incident fracture was observed in the subgroups with a prevalent vertebral fracture number of 0, with grade 0-2 vertebral deformity, or with lumbar BMD >=2.5 SD. Significant risk reduction was observed in all of the bone turnover marker and estimated glomerular filtration rate subgroups. In conclusion, once-weekly 56.5 MUg teriparatide injection reduced the vertebral fracture risk in patients with varying degrees of fracture risk, age, vertebral fracture number and grade, bone turnover level, and renal function. PMID- 24213217 TI - Role of local vitamin D signaling and cellular calcium transport system in bone homeostasis. AB - Mouse genetic studies have demonstrated that the 1,25-dihydroxyvitamin D [1,25(OH)2D] endocrine system is required for calcium (Ca(2+)) and bone homeostasis. These studies reported severe hypocalcemia and impaired bone mineralization associated with rickets in mutant mice. Specific phenotypes of these mice with an engineered deletion of 1,25(OH)2D cell signaling resemble the features observed in humans with the same congenital disease or severe 1,25(OH)2D deficiency. Decreased active intestinal Ca(2+) absorption because of reduced expression of epithelial Ca(2+) channels is a crucial mechanism that contributes to the major phenotypes observed in the mutant mice. The importance of intestinal Ca(2+) absorption supported by 1,25(OH)2D-mediated transport was further emphasized by the observation that Ca(2+) supplementation rescues hypocalcemia and restores bone mineralization in both patients and mice lacking 1,25(OH)2D signaling. This observation questions the direct role of 1,25(OH)2D signaling in bone tissue. Studies regarding tissue-specific manipulation of 1,25(OH)2D function have provided a consensus on this issue by demonstrating a direct action of 1,25(OH)2D on cells in bone tissue through bone metabolism and mineral homeostasis. In addition, movement of Ca(2+) from the bone as a result of osteoclastic bone resorption also provides a large Ca(2+) supply in Ca(2+) homeostasis; however, the system controlling Ca(2+) homeostasis in osteoclasts has not been fully identified. Transient receptor potential vanilloid (TRPV) 4 mediates Ca(2+) influx during the late stage of osteoclast differentiation, thereby regulating the Ca(2+) signaling essential for cellular events during osteoclast differentiation; however, the system-modifying effect of TRPV4 activity should be determined. Furthermore, it remains unknown how local Ca(2+) metabolism participates in systemic Ca(2+) homeostasis through bone remodeling. New insights are therefore required to understand this issue. PMID- 24213218 TI - Prevalence of knee pain, lumbar pain and its coexistence in Japanese men and women: The Longitudinal Cohorts of Motor System Organ (LOCOMO) study. AB - The Longitudinal Cohorts of Motor System Organ (LOCOMO) study was initiated in 2008 through a grant from the Ministry of Health, Labour, and Welfare of Japan to integrate information from several cohorts established for the prevention of musculoskeletal diseases. We integrated the information of 12,019 participants (3,959 men and 8,060 women) in the cohorts comprising nine communities located in Tokyo (two regions: Tokyo-1 and Tokyo-2), Wakayama [two regions: Wakayama-1 (mountainous region) and Wakayama-2 (seaside region)], Hiroshima, Niigata, Mie, Akita, and Gunma prefectures. The baseline examination of the LOCOMO study consisted of an interviewer-administered questionnaire, anthropometric measurements, medical information recording, X-ray radiography, and bone mineral density measurement. The prevalence of knee pain was 32.7 % (men 27.9 %; women 35.1 %) and that of lumbar pain was 37.7 % (men 34.2 %; women 39.4 %). Among the 9,046 individuals who were surveyed on both knee pain and lumbar pain at the baseline examination in each cohort, we noted that the prevalence of both knee pain and lumbar pain was 12.2 % (men 10.9 %; women 12.8 %). Logistic regression analysis showed that higher age, female sex, higher body mass index (BMI), living in a rural area, and the presence of lumbar pain significantly influenced the presence of knee pain. Similarly, higher age, female sex, higher BMI, living in a rural area, and the presence of knee pain significantly influenced the presence of lumbar pain. Thus, by using the data of the LOCOMO study, we clarified the prevalence of knee pain and lumbar pain, their coexistence, and their associated factors. PMID- 24213219 TI - Narrative medicine: caring for the sick is a work of art. PMID- 24213220 TI - A link between type 2 diabetes and brain function. PMID- 24213221 TI - Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways. AB - The aim of this study was to identify agents that regulate autophagy. A total of 544 differentially expressed genes were screened from the intersection set of GSE2435 and GSE31040, which was obtained from the Gene Expression Omnibus database and 19 differentially expressed kinases were selected according to a 'protein kinase database'. Gene ontology-biological process (GO-BP) enrichment analysis revealed that the 19 kinases were mainly associated with phosphorylation. The protein-protein interaction network exhibited 30 differentially expressed genes that interacted with BRAF, and GO-BP enrichment analysis showed the function of these genes were mainly involved in cell death and apoptosis. The kinase-kinase inhibitor regulatory network identified16 kinase inhibitors that specifically inhibited BRAF. Previous studies indicated that sorafenib is capable of regulating autophagy and regorafenib has also been reported; however, there have been no studies regarding the regulation of autophagy by afatinib, selumetinib, PD318088, axitinib, TAK-733, GDC-0980, GSK2126458, PLX-4720, AS703026, trametinib, GDC-0941 and PF-04217903. Thus, these kinase inhibitors are potential targets for further study on the regulation of autophagy in the future. PMID- 24213222 TI - Tertiary intratumor lymphoid tissue in colo-rectal cancer. AB - Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response. PMID- 24213224 TI - Surgical treatment of intra-abdominal desmoid tumors resulting in short bowel syndrome. AB - Advanced intra-abdominal desmoids tumors present with severe symptoms, complications or rapid growth, which lead to adverse outcomes. Our aim was to evaluate the treatment and outcome of patients with advanced intra-abdominal desmoids tumors, and develop guidelines for surgical management of these patients. We reviewed the clinical courses of 21 adult patients with advanced stage intra-abdominal desmoid tumors who presented to an intestinal rehabilitation and transplantation program. Patients with massive intestinal resection presented in two groups. The first group had a short small intestinal remnant after resection ( < 60 cm). These patients were poor rehabilitation candidates and eventually met criteria for transplant. The second had longer intestinal remnants and were more successfully rehabilitated and have not had complications that would lead to transplantation. Advanced intra-abdominal desmoid tumors have outcomes after resection that merit aggressive resection and planned intestinal rehabilitation and intestinal transplantation as indicated. PMID- 24213223 TI - Mixed Adenoneuroendocrine Carcinomas (MANECs) of the Gastrointestinal Tract: An Update. AB - The systematic application of immunohistochemical techniques to the study of tumors has led to the recognition that neuroendocrine cells occur rather frequently in exocrine neoplasms of the gut. It is now well known that there is a wide spectrum of combinations of exocrine and neuroendocrine components, ranging from adenomas or carcinomas with interspersed neuroendocrine cells at one extreme to classical neuroendocrine tumors with a focal exocrine component at the other. In addition, both exocrine and neuroendocrine components can have different morphological features ranging, for the former, from adenomas to adenocarcinomas with different degrees of differentiation and, for the latter, from well differentiated to poorly differentiated neuroendocrine tumors. However, although this range of combinations of neuroendocrine and exocrine components is frequently observed in routine practice, mixed exocrine-neuroendocrine carcinomas, now renamed as mixed adenoneuroendocrine carcinomas (MANECs), are rare; these are, by definition, neoplasms in which each component represents at least 30% of the lesion. Gastrointestinal MANECs can be stratified in different prognostic categories according to the grade of malignancy of each component. The present paper is an overview of the main clinicopathological, morphological, immunohistochemical and molecular features of this specific rare tumor type. PMID- 24213225 TI - Diagnosis and Treatment of Gastrinomas in Multiple Endocrine Neoplasia Type 1 (MEN-1). AB - Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease. It is associated with a broad range of endocrine tumours, most frequently arising in the parathyroid glands, the pituitary and the pancreas. Most neuroendocrine tumours will be diagnosed in the pancreas as non-functioning neuroendocrine tumours or insulinomas. Forty-two percent of the patients will develop a gastrin secreting neuroendocrine tumour, a gastrinoma. Gastrinomas in MEN-1 tend to be small, multiple and preferentially located in the duodenum. This paper will focus on the specific characteristics of gastrinomas in the setting of MEN-1 compared to sporadic gastrinomas. The developments in understanding the tumorigenesis of these tumours and the consequences for diagnosis and therapy will be discussed. PMID- 24213226 TI - Tumor-promoting circuits that regulate a cancer-related chemokine cluster: dominance of inflammatory mediators over oncogenic alterations. AB - Here, we investigated the relative contribution of genetic/signaling components versus microenvironmental factors to the malignancy phenotype. In this system, we took advantage of non-transformed fibroblasts that carried defined oncogenic modifications in Ras and/or p53. These cells were exposed to microenvironmental pressures, and the expression of a cancer-related chemokine cluster was used as readout for the malignancy potential (CCL2, CCL5, CXCL8, CXCL10). In cells kept in-culture, synergism between Ras hyper-activation and p53 dysfunction was required to up-regulate the expression of the chemokine cluster. The in vivo passage of RasHigh/p53Low-modified cells has led to tumor formation, accompanied by potentiation of chemokine release, implicating a powerful role for the tumor microenvironment in up-regulating the chemokine cluster. Indeed, we found that inflammatory mediators which are prevalent in tumor sites, such as TNFa and IL 1beta, had a predominant impact on the release of the chemokines, which was substantially higher than that obtained by the oncogenic modifications alone, possibly acting through the transcription factors AP-1 and NF-kB. Together, our results propose that in the unbiased model system that we were using, inflammatory mediators of the tumor milieu have dominating roles over oncogenic modifications in dictating the expression of a pro-malignancy chemokine readout. PMID- 24213227 TI - Fotemustine: a third-generation nitrosourea for the treatment of recurrent malignant gliomas. AB - Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas. PMID- 24213228 TI - Transition of treatment for patients with extra-abdominal desmoid tumors: nagoya university modality. AB - Treatment modalities for desmoid tumors have been changed because of the high recurrence rate, even after wide resection, and some cases experience spontaneous self-regression during clinical course. The treatment modality in our institutions before 2003 was surgical resection with wide surgical margin, however, meloxicam, which is a NSAID and a selective COX-2 inhibitor has been applied consecutively since 2003. We reviewed the previously reported outcomes of surgical and conservative treatment in our institutions. Among 30 patients receiving surgical treatment, 16 (53%) recurred. Younger age ( p < 0.05) was a significant poor factor. According to RECIST for meloxicam treatment, CR was in one, PR in 10, SD in eight, PD in one evaluated at 2011. Older age ( p < 0.01) was significantly associated with good outcome for meloxicam treatment. Results of the previous study indicated that surgical treatment alone could not control desmoid tumors, even with negative surgical margin. Considering the functional impairment resulting from surgery with negative surgical margin, a conservative and effective treatment modality with fewer complications is desired. Conservative treatment with meloxicam is a promising novel modality for patients with extra-abdominal desmoid tumors. PMID- 24213229 TI - PET-Guided Surgery - High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours. AB - Positron emission tomography (PET) with 11C-labeled 5-hydroxytryptophane (5-HTP) is a sensitive technique to visualize neuroendocrine tumours (NETs), due to high intracellular uptake of amine-precursors like L-dihydroxyphenylalanine (L-DOPA) and 5-HTP. NETs are often small and difficult to localize in spite of overt clinical symptoms due to hormonal excess. In our study, 38 consecutive NET patients underwent 11C-5-HTP-PET and morphological imaging by CT within 12 weeks prior to surgery. Surgical, histopathological and 5-HTP PET findings were correlated. 11C-5-HTP-PET corresponded to the surgical findings in 31 cases, was false negative in six, and true negative in one case resulting in 83.8% sensitivity and 100% specificity. Positive predicted value was 100%. In 11 patients 11C-5-HTP-PET was the only imaging method applied to localize the tumour. Thus, we could demonstrate that functional imaging by 11C-5-HTP-PET in many cases adds vital preoperative diagnostic information and in more than every fourth patient was the only imaging method that will guide the surgeon in finding the NET-lesion. Although the present results demonstrates that 11C-5-HTP may be used as an universal NET tracer, the sensitivity to visualize benign insulinomas and non functioning pancreatic NETs was lower. PMID- 24213230 TI - Medical treatment of gastroenteropancreatic neuroendocrine tumors. AB - Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient's preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors. PMID- 24213231 TI - Primary hepatic gastrinoma causing zollinger-ellison syndrome: a rare and challenging diagnosis. AB - The majority of gastrinomas causing Zollinger-Ellison syndrome (ZES) are located in the duodenum or the pancreas. Primary hepatic gastrinomas (PHG) are extremely rare and difficult to diagnose because the liver is the commonest site of metastatic disease and gastrinomas can be very small. Furthermore, gastrinomas are typically slow-growing thus a missed, occult primary tumour may not become evident for many years. The diagnosis of PHG is therefore dependent on a careful search for a primary and long-term biochemical follow-up following curative hepatic resection. We report a case of a 7 cm PHG in a 48 year old man with ZES. Preoperatively, both a basal and stimulated gastrin levels were elevated. Surgical exploration including intraoperative ultrasound and duodenotomy, failed to reveal a primary. Patient underwent a right hepatectomy. Yearly, gastrin and secretin stimulation tests remain normal 6 years following surgery. He remains symptom free off all medication. An additional 26 cases of PHG were found. Including this case, 21 had at least 1 year follow-up, however only eight had greater than 5 years (median 24 months). Post-op gastrin levels were reported in 25, however provocative testing was done in only 10. Persistence and recurrence occurred in one and four, respectively. PHG causing ZES is extremely rare. Although the current literature claims to include 26 additional cases of PHG, without a thorough search for the primary and long-term follow-up data including provocative testing, this diagnosis remains a challenge. PMID- 24213232 TI - Chromogranin a as serum marker for gastroenteropancreatic neuroendocrine tumors: a single center experience and literature review. AB - The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA), urinary 5-hydroxyindoleacetic acid (5-HIAA) and alkaline phosphatase (AP) in neuroendocrine tumors (NETs) of the GastroEnteroPancreatic-(GEP-) system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62) and pancreatic (n = 48) NETs. CgA levels were analyzed by a commercially-available immunoradiometric assay (CIS-bio) during routine follow-up in the years 2000 2009. CgA showed a higher sensitivity for midgut (68%) than pancreatic (54%) NETs. A higher CgA sensitivity and significantly higher median CgA values were found in patients with liver metastases than in those without, and in patients with hepatic and additionally extra-hepatic metastases than in those with hepatic and nodal metastases alone, respectively. We found an overall sensitivity for elevated 5HIAA excretion of 69% for midgut NETs and a significant correlation between median CgA and 5-HIAA values. The sensitivity of AP and the correlations of AP/CgA-data-pairs were low in both midgut and pancreatic NETs, although highest for metastatic pancreatic NETs. The sensitivity of CgA measurement depends on the NET primary location and spread of disease. 5-HIAA and CgA showed comparable sensitivity in midgut NETs, while AP does not seem to be useful as a tumor marker in GEP-NETs. PMID- 24213233 TI - Does secondary inflammatory breast cancer represent post-surgical metastatic disease? AB - The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC at the traumatized site that have been identified by our IBC Registry (IBCR) and hypothesize that angiogenesis appearing as part of the healing process could act as an accelerant to an otherwise latent breast malignancy. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer. PMID- 24213234 TI - Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in Japan. AB - Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer. PMID- 24213235 TI - Desmoid tumors in pregnant and postpartum women. AB - We report here a review of the current medical literature on pregnancy associated desmoids, including 10 cases of our own. The pertinent findings are that a large percentage of desmoids in females arise in and around pregnancy. Most occur in the abdominal muscles, particularly the right rectus abdominus, perhaps related to trauma from abdominal stretching and fetal movement. While these tumors may regress spontaneously after delivery most can be surgically resected with low recurrence rates even with R1 resections and this is clearly the treatment of choice. Subsequent pregnancies do not appear to result in recurrence in either FAP or non FAP patients. It is not clear from currently available data whether pregnancy associated desmoids are molecularly distinct from other desmoids. PMID- 24213238 TI - Diagnostic Value of 11C-Methionine (MET) and 18F-Fluorothymidine (FLT) Positron Emission Tomography in Recurrent High-Grade Gliomas; Differentiation from Treatment-Induced Tissue Necrosis. AB - We retrospectively evaluated the usefulness of combined measurement of L-methyl [11C]methionine (MET) and 3'-deoxy-3'-[18F]fluorothymidine (FLT) positron emission tomography (PET) in the differential diagnosis between recurrent gliomas and necrotic lesions. Twenty-one patients with high-grade glioma, previously treated with surgery and radiotherapy with chemotherapy and first radiological suspicion of recurrence were enrolled. The uptake was assessed by the maximum standardized uptake value (SUVmax) and lesion-to-normal tissue count density ratio (L/N ratio). Of the 21 lesions, 15 were diagnosed recurrent gliomas and six were necrotic lesions. The average SUVmax was not significantly different between recurrent gliomas and necrotic lesions on either MET-PET or FLT-PET. The average L/N ratio of recurrent gliomas (3.36 +/- 1.06) was significantly higher than that of necrotic lesions (2.18 +/- 0.66) on MET-PET (p < 0.01) and the average L/N ratio of recurrent gliomas (7.01 +/- 2.26) was also significantly higher than that of necrotic lesions (4.60 +/- 1.23) on FLT-PET (p < 0.01). ROC curve analysis showed that the areas under the curves were high but not different between MET- and FLT-PET. PET studies using MET and FLT are useful in the differentiation of recurrent glioma from treatment-induced necrotic lesion. However, there is no complementary information in the differentiation with simultaneous measurements of MET- and FLT-PET. PMID- 24213236 TI - Tumor-associated antigens for specific immunotherapy of prostate cancer. AB - Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody based strategies with radio-, hormone-, chemo- or antiangiogenic therapy. PMID- 24213237 TI - Tumor microenvironment in the brain. AB - In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context. PMID- 24213239 TI - Radiation therapy for the treatment of recurrent glioblastoma: an overview. AB - Despite the therapeutic advances in neuro-oncology, most patients with glioblastoma ultimately experience local progression/relapse. Re-irradiation has been poorly viewed in the past, mainly due to the overestimated risk of side effects using conventional radiotherapy. To date, thanks to the improvement of several delivery techniques, together with improved imaging capabilities, re irradiation is a viable salvage treatment option to manage such clinical scenario. A literature overview on the feasibility and efficacy of the different irradiation modalities for recurrent glioblastoma along with considerations on areas of improvement are provided. PMID- 24213240 TI - Epithelial-mesenchymal transition is a critical step in tumorgenesis of pancreatic neuroendocrine tumors. AB - The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs. PMID- 24213241 TI - Desmoid tumors in the pediatric population. AB - Desmoid tumors are benign soft tissue tumors associated with locally aggressive growth and high rates of morbidity, but they do not metastasize via lymphatic or hematogenous routes. While most of the data on desmoid tumors originates in the adult literature, many of the findings have been applied to the management of pediatric patients. This article discusses the epidemiology, etiology, clinical presentation, pathology, and treatment of this rare tumor in the pediatric population and includes a literature review of the most recent large series of pediatric patients with desmoid tumors. PMID- 24213242 TI - Postoperative radiation therapy for non-small cell lung cancer and thymic malignancies. AB - For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use. PMID- 24213243 TI - Exercise DVD effect on musculoskeletal disorders in professional orchestral musicians. AB - BACKGROUND: Professional musicians report a high prevalence of performance related musculoskeletal disorders (PRMDs). Excessive muscle tension and fatigue have been reported as important factors contributing to PRMDs. AIMS: To evaluate feasibility and effectiveness of a specific exercise programme delivered via a digital video disc (DVD) targeting PRMDs and associated risk factors. METHODS: Volunteers from eight Australian symphony orchestras undertook two or more sessions per week over 12 weeks. Questionnaires were administered pre- and post intervention with items including the frequency and severity of PRMDs, perceived exertion during different playing situations, per formance effects of the DVD and satisfaction rates. Musicians who had also participated in an equivalent face-to face programme prior to this DVD trial compared the two interventions. RESULTS: One hundred and forty-four out of 576 musicians volunteered (25% uptake), and 50 participants completed a mean 2.1 (SD 0.42) sessions over the 12 week period (41% compliance). PRMD frequency and severity were significantly reduced post intervention (P < 0.01). Participants reported benefits of the DVD on strengthening muscles, increasing ease of movement and improving flexibility related to playing. Despite this, perceived exertion levels during private practice, rehearsal and performance remained the same (not significant). Seventy eight per cent of participants scored their overall experience of the use of the DVD as good or excellent. Owing to its convenience and detailed exercise demonstrations, the DVD was rated as better or much better overall than the face to-face classes by 55% of participants who had experienced both. CONCLUSIONS: An exercise DVD was well received and appeared to be effective, convenient and safe in managing occupational-specific musculoskeletal disorders in musicians. PMID- 24213246 TI - A conformational factorisation approach for estimating the binding free energies of macromolecules. AB - We present a conformational factorization approach. The theory is based on a superposition partition function, decomposed as a sum over contributions from local minima. The factorisation greatly reduces the number of minima that need to be considered, by employing the same local configurations for groups that are sufficiently distant from the binding site. The theory formalises the conditions required to analyse how our definition of the binding site region affects the free energy difference between the apo and holo states. We employ basin-hopping parallel tempering to sample minima that contribute significantly to the partition function, and calculate the binding free energies within the harmonic normal mode approximation. A further significant gain in efficiency is achieved using a recently developed local rigid body framework in both the sampling and the normal mode analysis, which reduces the number of degrees of freedom. We benchmark this approach for human aldose reductase (PDB code 2INE). When varying the size of the rigid region, the free energy difference converges for factorisation of groups at a distance of 14 A from the binding site, which corresponds to 80% of the protein being locally rigidified. PMID- 24213244 TI - Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome. AB - Patient-specific induced pluripotent stem cells (iPSCs) will assist research on genetic cardiac maladies if the disease phenotype is recapitulated in vitro. However, genetic background variations may confound disease traits, especially for disorders with incomplete penetrance, such as long-QT syndromes (LQTS). To study the LQT2-associated c.A2987T (N996I) KCNH2 mutation under genetically defined conditions, we derived iPSCs from a patient carrying this mutation and corrected it. Furthermore, we introduced the same point mutation in human embryonic stem cells (hESCs), generating two genetically distinct isogenic pairs of LQTS and control lines. Correction of the mutation normalized the current (IKr) conducted by the HERG channel and the action potential (AP) duration in iPSC-derived cardiomyocytes (CMs). Introduction of the same mutation reduced IKr and prolonged the AP duration in hESC-derived CMs. Further characterization of N996I-HERG pathogenesis revealed a trafficking defect. Our results demonstrated that the c.A2987T KCNH2 mutation is the primary cause of the LQTS phenotype. Precise genetic modification of pluripotent stem cells provided a physiologically and functionally relevant human cellular context to reveal the pathogenic mechanism underlying this specific disease phenotype. PMID- 24213245 TI - Large cargo transport by nuclear pores: implications for the spatial organization of FG-nucleoporins. AB - Nuclear pore complexes (NPCs) mediate cargo traffic between the nucleus and the cytoplasm of eukaryotic cells. Nuclear transport receptors (NTRs) carry cargos through NPCs by transiently binding to phenylalanine-glycine (FG) repeats on intrinsically disordered polypeptides decorating the NPCs. Major impediments to understand the transport mechanism are the thousands of FG binding sites on each NPC, whose spatial distribution is unknown, and multiple binding sites per NTR, which leads to multivalent interactions. Using single molecule fluorescence microscopy, we show that multiple NTR molecules are required for efficient transport of a large cargo, while a single NTR promotes binding to the NPC but not transport. Particle trajectories and theoretical modelling reveal a crucial role for multivalent NTR interactions with the FG network and indicate a non uniform FG repeat distribution. A quantitative model is developed wherein the cytoplasmic side of the pore is characterized by a low effective concentration of free FG repeats and a weak FG-NTR affinity, and the centrally located dense permeability barrier is overcome by multivalent interactions, which provide the affinity necessary to permeate the barrier. PMID- 24213249 TI - Flow disturbances in stent-related coronary evaginations: a computational fluid dynamic simulation study. AB - AIMS: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. METHODS AND RESULTS: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross-sectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. CONCLUSIONS: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size. PMID- 24213248 TI - The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures. AB - Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 MUM) and kainic acid (IC50: 0.81, 2.0, 6.2 MUM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 MUM, TAT-D: 7.1 MUM, penetratin/Pep-1: >10 MUM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to deliver neuroprotective drugs to the CNS following injury and/or potential neuroprotectants in their own right. PMID- 24213247 TI - The involvement of microRNAs in major depression, suicidal behavior, and related disorders: a focus on miR-185 and miR-491-3p. AB - Major depressive disorders are common and disabling conditions associated with significant psychosocial impairment and suicide risk. At least 3-4 % of all depressive individuals die by suicide. Evidence suggests that small non-coding RNAs, in particular microRNAs (miRNAs), play a critical role in major affective disorders as well as suicide. We performed a detailed review of the current literature on miRNAs and their targets in major depression and related disorders as well as suicidal behavior, with a specific focus on miR-185 and miR-491-3p, which have been suggested to participate in the pathogenesis of major depression and/or suicide. miRNAs play a fundamental role in the development of the brain. Several miRNAs are reported to influence neuronal and circuit formation by negatively regulating gene expression. Global miRNA reduced expression was found in the prefrontal cortex of depressed suicide completers when compared to that of nonpsychiatric controls who died of other causes. One particular miRNA, miR-185, was reported to regulate TrkB-T1, which has been associated with suicidal behavior upon truncation. Furthermore, cAMP response element-binding protein brain-derived neurotrophic factor pathways may regulate, through miRNAs, the homeostasis of neural and synaptic pathways playing a crucial role in major depression. miRNAs have gained attention as key players involved in nervous system development, physiology, and disease. Further evidence is needed to clarify the exact role that miRNAs play in major depression and related disorders and suicidal behavior. PMID- 24213251 TI - Identification of an RFLP marker tightly linked to theHt1 gene in maize. AB - We have identified tight linkage of an RFLP marker to theHt1 gene of maize that confers resistance to the fungal pathogenHelminthosporium turcicum race 1. This was accomplished by the use of four pairs of near isogenic lines (NILs; B73, A619, W153R, and CM105), each differing by the presence or the absence of the geneHt1. SinceHt1 maps to chromosome 2, 26 clones already mapped to this chromosome were labeled and probed against Southern blots of these NILs DNA digested with three restriction enzymes:EcoRI,BamHI, andHindIII. Six markers exhibited an RFLP for at least one pair of NILs. Presumptive linkage was further tested by analyzing the segregation of five of the six markers (one was monomorphic in the cross studied) and resistance toH. turcicum race 1 on 95 F2 individuals from the cross DF20 * LH146Ht. The results indicate a tight linkage between one of the DNA markers,UMC150B, and theHt1 gene. PMID- 24213252 TI - Genetics of leaf blight resistance in wheat. AB - Studies on the genetics of leaf blight caused byAlternaria triticina using generation mean analysis revealed that additive components played a major role, but that dominance components also contributed significantly in controlling the variability for leaf blight resistance in wheat crosses. Furthermore, the additive x additive type of epistasis was predominant in the first three crosses, whereas in the fourth cross additive x dominance (j) and dominance x dominance (1) components of epistasis were most significant. Because of this it may be desirable to follow a simple recurrent selection scheme for higher tolerance, to isolate resistant plants from the segregating populations derived from crosses of parents of diverse origin following the pedigree method of breeding. CPAN-1887 was very tolerant to leaf blight in the present study and should be utilized in hybridization programs to develop leaf-blight-resistant varieties. PMID- 24213253 TI - Selection and characterization of a rice mutant resistant to 5-methyltryptophan. AB - A rice plant resistant to 5-methyltryptophan (5MT) was selected from mutagenized M3 seeds (Oryza sativa L. var. Sasanishiki) originating from panicles treated with ethylene imine (0.2%) 2 h after flowering. When germinated on 5MT-containing medium, the seeds (M4) from selfed plants segregated with a 3 resistant:1 sensitive ratio, indicating that the plant was heterozygous for a resistance gene and that the resistance was dominant. The resistance was also expressed in callus derived from seeds. Analysis of the free amino acids in seeds, seedlings, and calli showed that homozygous resistant plants (TR1) contained higher levels of total free amino acids than sensitive plants. In particular the levels of tryptophan, phenylalanine, and histidine were, respectively, 8.5, 5.4, and 4.9 times higher than those in the sensitive plants. PMID- 24213250 TI - Effects and mechanisms of working memory training: a review. AB - Can cognitive abilities such as reasoning be improved through working memory training? This question is still highly controversial, with prior studies providing contradictory findings. The lack of theory-driven, systematic approaches and (occasionally serious) methodological shortcomings complicates this debate even more. This review suggests two general mechanisms mediating transfer effects that are (or are not) observed after working memory training: enhanced working memory capacity, enabling people to hold more items in working memory than before training, or enhanced efficiency using the working memory capacity available (e.g., using chunking strategies to remember more items correctly). We then highlight multiple factors that could influence these mechanisms of transfer and thus the success of training interventions. These factors include (1) the nature of the training regime (i.e., intensity, duration, and adaptivity of the training tasks) and, with it, the magnitude of improvements during training, and (2) individual differences in age, cognitive abilities, biological factors, and motivational and personality factors. Finally, we summarize the findings revealed by existing training studies for each of these factors, and thereby present a roadmap for accumulating further empirical evidence regarding the efficacy of working memory training in a systematic way. PMID- 24213254 TI - Novel seed lipid phenotypes in combinations of mutants altered in fatty acid biosynthesis inArabidopsis. AB - The seed fatty acid (FA) composition of various single mutant combinations ofArabidopsis thaliana that affect FA biosynthesis has been examined. Double mutant combinations offae, a mutation affecting CIS elongation, and a series of four other FA biosynthetic mutants were synthesized. The four other single mutants were:fad2 andfad3, which are deficient in 18?1 and 18?2 desaturation, respectively;fab1, which is elevated in 16?0 and decreased in 18?1; andfab2, which is elevated in 18?0 and decreased in 18?1. The superimposition of two blocks in the FA biosynthetic pathway leads to dramatic changes in the FA content of the double mutants. The tenArabidopsis stocks analyzed to date (wild-type, five single mutants, and four double mutants) make seed oils with a wide range of FA compositions, and illustrate the diversity of oils it is possible to obtain from a single plant species. PMID- 24213255 TI - Normalization of the DNA content of telophase cells from wheat calli by nutrient modifications. AB - Cytophotometric analyses were conducted to determine whether the DNA content of wheat callus varied by tissue culture medium or age of callus. Wheat,Triticum aestivum L. line PCYT-20, was cultured on three variations of the Murashige and Skoog (1962) growth medium. At the end of 2, 4, 6 and 8 weeks, samples were collected and prepared for Feulgen cytophotometry. Standards for the DNA measurements were readings from 100 telophase nuclei in wheat meristematic root tips. Amounts of DNA per nucleus present in telophase cells from callus grown on single-strength MS indicated that ploidy level increased 52%, 74% and 39%, respectively, over time from 2, 4, and 6 weeks as compared to the double-strength MS medium, and 29%, 60% and 32%, respectively, when coconut water was added to the single-strength MS culture medium. The shape of the mitotically-active cells in callus was more variable than in root tips cells. Callus grown on double strength MS medium produced more shoots than callus grown on single-strength MS. Double-strength MS medium and, to a lesser extent, additional sucrose and organic nitrogen overcame the effects of 2,4-D on DNA amplification. Improved media may reduce the somaclonal variation induced by tissue culture. PMID- 24213256 TI - Nuclear genes affecting percentage of green plants in barley (Hordeum vulgare L.) anther culture. AB - The genetics behind response in barley anther culture was studied with 22 reciprocal and one single: cross between three varieties with high and four varieties with low capacity for green plant formation. Effects of genotypes dominated embryo formation and percentages of green plants, accounting for 62 and 76% of total variation, respectively, with almost no genetic effect on the ability to regenerate plants from pollen embryos. Nuclear genes could explain all genotype effects in this plant material, since no reciprocal effects were indicated. The three parents with high and the four parents with low capacity for green plant formation formed two phenotypically homogeneous groups, producing 27 52% and 0-7% green plants, respectively. Genetic variation within hybrids for both embryo and green plant formation could be explained completely by general combining ability (GCA). The results are discussed with respect to a previous similar study in hexaploid wheat and the reported existence of DNA deletions in the plastid genomes in albino plants from anther culture of wheat and barley. PMID- 24213257 TI - Bias of maximum likelihood estimator of intraclass correlation. AB - A bias correction was derived for the maximum likelihood estimator (MLE) of the intraclass correlation. The bias consisted of two parts: a correction from MLE to the analysis of variance estimator (ANOVA) and the bias of ANOVA. The total possible bias was always negative and depended upon both the degree of correlation and the design size and balance. The first part of the bias was an exact algebraic expression from MLE to ANOVA, and the corrected estimator by this part was ANOVA. It was also shown that the first correction term was equivalent to Fisher's reciprocal bias correction on hisZ scores. The total possible bias of MLE was large for small and moderate samples. Relative biases were larger for small parametric values and vice versa. To ensure a relative bias less than 10% assuming an intraclass correlation of 0.025, which is not unusual in most of the animal genetic studies, the total number of observations (N) should be not less than 500. From a design point of view, minimum bias occurred atn = 2, the minimum family size possible, underN fixed. PMID- 24213258 TI - The role of hybridization in the karyotype evolution of deer (Cervidae; Artiodactyla; Mammalia). AB - The karyotypes of 46 animals from a population ofCervus elaphus, Cervus nippon, and hybridsCervus elaphus xCervus nippon were studied using G- and C-banding techniques. It was found that four chromosome pairs known from the karyotype ofCervus elaphus are involved in two systems of Robertsonian translocations. Pedigree analysis supports the hypothesis of a simple Mendelian inheritance of each translocation system. With respect to these translocation systems, the population shows no significant deviation from the corresponding Hardy-Weinberg structure. Thus, hybridization events can be accepted as a major factor in karyotype evolution of deer. PMID- 24213259 TI - Somaclonal variation in tuber disc-derived populations of potato : I. Evidence of genetic stability across tuber generations and diverse locations. AB - Approximately 1,600 potato (Solanum tuberosum L.) plants of the cultivar 'Superior' were regeneratedin vitro from meristems adventitiously initiated on tuber disc expiants. Direct regeneration from tuber disc cells, by passing a callus intermediary, is efficient and results in low frequencies of plants with gross phenotypic aberrations. The somaclonal plant population was statistically characterized in field plots over five asexual generations and in three diverse locations. When compared in advanced generations to a large population of control plants propagated from stem cuttings, the means of the somaclonal population were significantly different, often shifted in the desirable direction, for 16 of 22 horticulturally important traits. Somaclonal population variances statistically exceeded those of the controls for 13 of the 22 traits. Regressions between consecutive tuber generations and between locations or replications (blocks) within a generation were significant in the somaclonal population for all traits analyzed. In a few instances, significant control population regressions occurred that are interpreted to be the result of non-random, non-genetic factors primarily affecting control plants of low vigor. Selected somaclones exhibiting desirable alterations for yield, tuber number and shape, and vigor were stable over more than two consecutive asexual generations. PMID- 24213260 TI - Chromosome pairing relationships among the A, B, and D genomes of bread wheat. AB - Chromosome pairing and chiasma frequency were studied in bread wheat euhaploids (2n = 3x = 21; ABD genomes) with and without the major pairing regulatorPh1. This constitutes the first report of chromosome pairing relationships among the A, B, and D genomes of wheat without the influence of an alien genome. AllPh1 euhaploids had very little pairing, with 0.62-1.05 rod bivalents per cell; ring bivalents were virtually absent and mean arm-binding frequency (c) values ranged from 0.050 to 0.086. In contrast, theph1b euhaploids had extensive homoeologous pairing, with chiasma frequency 7.5-11.6 times higher than that in thePh1 euhaploids. They had 0.53-1.16 trivalents, 1.53-1.74 ring bivalents, and 2.90 3.57 rod bivalents, withc from 0.580 to 0.629. N-banding of meiotic chromosomes showed strongly preferential pairing between chromosomes of the A and D genomes; 80% of the pairing was between these genomes, especially in the presence of theph1b allele. The application of mathematical models to unmarked chromosomes also supported a 2?1 genomic structure of theph1b euhaploids. Numerical modeling suggested that about 80% of the metaphase I association was between the two most related genomes in the presence ofph1b, but that pairing under Ph1 was considerably more random. The data demonstrate that the A and D genomes are much more closely related to each other than either is to B. These results may have phylogenetic significance and hence breeding implications. PMID- 24213261 TI - Fertile somatic hybrids between transgenicNicotiana tabacum and transgenicN. debneyi selected by dual-antibiotic resistance. AB - A simple, yet effective selection system was used to produce fertile somatic hybrids betweenNicotiana tabacum andN. debneyi. This approach utilized transgenic antibiotic-resistantN. tabacum andN. Debneyi as donor plants for mesophyll protoplast fusions. Thirteen somatic hybrid plants were regenerated from calli capable of growth on medium containing both antibiotics. The majority of the hybrids displayed a range of leaf and floral morphologies and growth habits that were intermediate to those of the parental species, and had chromosome numbers varying from amphidiploid (2n = 96) to hypoaneuploid (2n = 60). Isoenzyme and RFLP analysis demonstrated the presence and expression of nuclear genes from both parents in all of the hybrids. Most plants are fully fertile. Thus, these plants differ from the malesterile tobacco 'cybrids' and alloplasmic lines produced by transferring theN. debneyi cytoplasm to tobacco. A nonrandom pattern of cytoplasmic segregation in the fusion products occurred with a bias towards the presence ofN. debneyi cp and mtDNA. Evidence for the presence of rearranged or recombinant cp and mtDNA in some of the hybrids was obtained. The somatic hybrids were successfully backcrossed to theN. tabacum parent and are now being tested for immunity to black root rot, a trait specific toN. debneyi, but not existent in theN. tabacum parental line. PMID- 24213262 TI - An approximate method for optimum independent culling level selection for n stages of selection with explicit solutions. AB - An approximate method with explicit solutions to apply independent culling levels for multiple traits in n-stages of selection was developed. An approximate solution was found for sequentially selected traits. Two assumptions were necessary. The first was to assume that subsequent selection would not appreciably change the mean of traits already selected, and the second was to approximate the variance of a correlated trait in a selected population with an upward biased projection. The procedure was shown to give near optimal results regardless of selection intensity or genetic correlations if phenotypic correlations among traits were low. The procedure gave poor results only for certain sequences of selection when phenotypic correlations were high. However, in those cases good results were obtained using a different sequence of selection. With high correlations, the procedure is recommended only after comparing solutions and expected genetic gain for all sequences of selection. If the expected aggregate gain for the sequence of selection desired is less than that of another order, culling points associated with the optimal ordering must be determined. Genetic gain from use of culling points is independent of order of selection. The procedure is recommended for use with computer programs that attempt to find optimal culling points to reduce computational time and to check results. PMID- 24213263 TI - PCR detection of transcripts homologous to the self-incompatibility gene in anthers ofBrassica. AB - The polymerase chain reaction (PCR) is particularly well suited for the detection of rare sequences. Taking advantage of the recent isolation of sequences associated with stigma self-incompatibility inBrassica oleracea, we used PCR amplifications with primers synthesized to the S6 cDNA sequence, to demonstrate the presence of mRNA homologous to stigmaS-locus gene (SLG) in anthers during early microsporogenesis. In addition, otherS-locus-related (SLR) sequences were shown to be transcribed in sexual as well as in vegetative tissues (roots, leaves), suggesting that the SLG family might be involved not only in pollen stigma recognition, but more generally in various forms of plant cell signalling processes. This information corroborates the recent discovery of a cDNA-deduced protein kinase from maize roots, whose extracellular receptor displays high homology withBrassica S-locus-specific glycoproteins. PMID- 24213264 TI - Parentage determination in maize hybrids using the arbitrarily primed polymerase chain reaction (AP-PCR). AB - Using a novel procedure based on the polymerase chain reaction, we have developed a rapid, efficient, and economical method for identifying plant genotypes. The arbitrarily primed polymerase chain reaction (AP-PCR) generates reproducible fingerprints from any organism, without the need for DNA sequence information. These fingerprints include DNA fragment polymorphisms that can be (1) used for varietal identification and parentage determination, (2) followed in segregating populations produced by crosses, (3) used as markers for the construction of genetic maps, and (4) used to generate dendograms of phylogenetic relationships, especially at the intraspecific level. AP-PCR requires only minute quantities of DNA (10-25 ng per reaction) and therefore can be used in situations in which DNA is limiting. We demonstrate the use of AP-PCR to identify inbred parents of hybrid maize plants in double-blind experiments. PMID- 24213265 TI - Inheritance of chloroplast DNA inPopulus. AB - Restriction fragment length polymorphisms (RFLPs) were used as markers to determine the transmission of chloroplast DNA (cpDNA) in poplar crosses. The plant material studied included individual trees ofPopulus trichocarpa, P. maximowiczii xtrichocarpa, P. maximowiczii xnigra, and offspring from controlled crosses between these trees. RFLPs were identified by direct observation of stained restriction fragments, as well as by molecular hybridization with heterologous cpDNA probes. Analysis of the restriction fragment patterns in the parents and their progeny showed only the patterns of the maternal tree in the progeny, while no paternal type was found. These results provide clear evidence of a maternal mode of chloroplast inheritance in the poplar clones studied. PMID- 24213266 TI - Chromosomal localization and genomic organization of alpha-amylase genes in rice (Oryza sativa L.). AB - Genes for alpha-amylase, alcohol dehydrogenase, andEm, an ABA-regulated gene expressed late in embryogenesis, were localized on rice chromosomes by the analysis of primary trisomies. The validity of the mapping approach was confirmed usingAdh-1 as a control. TheAdh-1 gene has previously been assigned to chromosome 11 using conventional techniques. In this study we confirm this assignment and report an additional locus for alcohol dehydrogenase (Adh-2) on chromosome 9. The alpha-amylase genes were located on chromosomes 1, 2, 6, 8, and 9 while theEm gene was mapped to chromosome 5. To facilitate trisomic analysis and correlation of cloned genes with bands observed on Southern blots, a nomenclature for the rice alpha-amylase genes has been proposed. In addition to mapping nine cloned alpha-amylase genes, we have identified two previously uncloned alpha-amylase genes as part of this study. Polymorphism for alpha-amylase genes belonging to each of the three subfamilies was observed between M202 and IR36. The maximum degree of polymorphism was found among genes belonging to the RAmy3 subfamily, which also has the most diverse group of genes. PMID- 24213267 TI - Restriction fragment length polymorphism analysis of polymerase chain reaction products amplified from mapped loci of rice (Oryza sativa L.) genomic DNA. AB - Thirty mapped Indica rice genomic (RG) clones were partially sequenced from each end. From such sequence data, pairs of oligonucleotides were synthesized to act as primers for polymerase chain reaction (PCR) amplification of the corresponding loci in crude total DNA preparations. The PCR products from DNA of Indica varieties were of the sizes expected from the sizes of the corresponding RG clones. However, size polymorphisms were seen between PCR products from Indica and Japonica varieties, and among wildOryza species. Restriction fragment length polymorphism (RFLP) was observed between PCR products of Indica varieties simply by electrophoretic analysis of restricted products, without the need for Southern hybridization or radiolabelling. The RFLPs noted between varieties ARC6650 and Phalguna were inherited in recombinant inbred lines derived from a cross between them. The RFLPs were detectable in PCR products amplified from DNA extracted by a simple procedure from single seedlings or leaves, and revealed genetic heterogeneity in cultivated lines. An approach is described that is relevant to the acceleration of classical plant breeding through molecular techniques. PMID- 24213268 TI - Heritability of morphological characters used to distinguish European and Africanized honeybees. AB - Identification of "Africanized" honeybees (Apis mellifera) is usually achieved by measuring an array of morphological characters. Discriminant functions exist that allow determination of subspecies similarity on the basis of these measurements. Here we compute the heritabilities of the standard character set for ten eco types (Table 1) of bees. Heritability is extremely high for body size characters and there is greater genetic variance among ecotypes than within. Heritability is lower, but still very high, for the vein angle characters and hamuli number (Table 3). Heritability was also computed for the same character set for a group of 20 colonies in Venezuela (Table 4). Heritabilities declined by an average of 41% when specimens were reared in nonmaternal environments, but were still extremely high for the body size characters. These results support the continued use of morphological characters as a tool for identifying Africanized bees. They also suggest that multivariate analysis of morphology is useful in evaluating changes in the honeybee genome, and is therefore an effective means of studying the population genetics of honeybees. PMID- 24213269 TI - Genetic properties of four types of stability parameter. AB - The genetic properties of four types of stability parameter for individual genotypes were investigated using a set of diallel cross data (28 genotypes x four locations x 3 years). The specific parameters studied were: the variance of a genotype across environments (T1); the genotype x environment (GE) interaction effect for a genotype, squared and summed across all environments (T2); the residual mean square (MS) of deviations from the regression of a genotype on an environmental index (T3); and years within locations MS for a genotype, averaged over all locations (T4). Each stability statistic was fitted to the additive model, based on the assumption that if the stability parameter is heritable, stability of F1 is most likely to be the average stability of its parents. The results showed that T1 and T4 were additive, but T2 and T3 were not. A study of the consistency of stability rankings between two seeding rates over the same set of environments showed a similar pattern. It appears that stability parameters of types 1 and 4 are heritable, and thus useful for selection, while those of types 2 and 3 are nonheritable, and thus not useful. PMID- 24213270 TI - Paternal leakage of mitochondrial DNA inPinus. AB - We studied mitochondrial DNA restriction fragment length polymorphism in 11 parents and 125 seedlings of 23 controlled matings within and between jack pine (Pinus banksiana Lamb.) and lodgepole pine (P. contorta Dougl.). A potential mitochondrial distinction between these two conifers was evident in the parental samples. Only maternal mitochondrial restriction fragments were observed in a majority of the seedlings, which is consistent with results from angiosperms and other members of the genusPinus L. However, we detected exclusively paternal mitochondrial DNA in six of the seedlings. These unusual seedlings were not attributable to heteroplasmy or contamination of the experimental material, indicating that mitochondrial inheritance was not strictly maternal. Paternal mitochondrial leakage inPinus may permit novel insights into the transmission genetics and evolution of organellar polymorphisms. PMID- 24213271 TI - The microspore-derived embryo ofBrassica napus L. as a tool for studying embryo specific lipid biogenesis and regulation of oil quality. AB - A time-course study of lipid accumulation in microspore-derived embryos and developing zygotic embryos of rapeseed (Brassica napus L. ssp.oleifera) is presented. Rapid storage fat (triacylglycerol) biosynthesis was induced in microspore-derived embryos of oilseed rape (cv 'Topas') when the embryos were transferred from standing cultures (10 ml) to fresh medium (75 ml) and shake cultured. Triacylglycerols accumulated, after a lag period of 7 days, at a linear rate of approximately twice that of the developing zygotic embryo. The fatty acid composition of triacylglycerols in microspore-derived embryos closely parallelled that of the developing zygotic embryos. In the microspore-derived embryos, the amount of phosphatidylcholine, the major substrate for the production of polyunsaturated fatty acids in oilseeds, remained constant during the linear phase of triacylglycerol production, whereas it increased steadily in the zygotic embryos. The fatty acid composition of individual cotyledons from microspore embryos shake cultured for 15 days was compared with that of individual mature seeds. Relative amounts of the major fatty acids, i.e. palmitic, oleic and linoleic acids, were essentially the same, whereas the microspore-derived embryos had about 35% less stearic acid and 35% more linolenic acid than the mature seeds. Variation in the amounts of oleic, linoleic and linolenic acids between seeds was similar to that found between cotyledons of microspore-derived embryos, whereas variation in palmitic and stearic acid levels was significantly lower between microsporederived cotyledons than between the seeds. The results indicate that microspore-derived embryos from shake cultures should be convenient for use in studying the regulation of oil biosynthesis and for rapidly screening for oil quality in genetically altered rapeseed. PMID- 24213272 TI - Efficient interspecific hybridization in the genusHelianthus via "embryo rescue" and characterization of the hybrids. AB - With the aid of the "embryo rescue" technique, interspecific hybrids in the genusHelianthus could be raised with a recovery rate of 41%. Altogether, 33 different hybrid combinations were realized using the cultivated form, both as a female and male parent. The hybrids obtained have been identified by different methods, i.e., by comparison of leaf morphology, pollen stainability, chromosome number and by RFLP analysis. The former three methods are useful to obtain global information, while the RFLP analysis allows a rapid and safe characterization in early developmental stages of the hybrids. PMID- 24213274 TI - Partial auricular reconstruction with porous polyethylene frameworks and superficial temporoparietal fascia flap. AB - Untreated acquired auricular damage can be a psychological burden, especially for younger patients. The significance of auricular reconstruction in patients with microtia in terms of quality of life has already been demonstrated. In these patients the use of porous polyethylene combined with a temporoparietal fascia flap has proven to be a suitable method for achieving good cosmetic results. Here, we describe how to use porous polyethylene combined with an endoscopically harvested temporoparietal fascia flap and autologous skin grafts for the reconstruction of acquired partial auricle defects and present outcomes and patient benefit. Ten consecutive patients were asked to answer validated questionnaires [modified Glasgow Benefit Inventory (GBI)] determining the effects of partial ear reconstruction on their health-related quality of life. These patients were seen regularly in our outpatient clinic for documentation and postoperative counseling. All patients returned a valid questionnaire; 80% were satisfied with the esthetic result. In retrospect, all patients would again decide to undergo surgery. The mean total GBI score was 27.8 (median 29.2, p < 0.05) reflecting an improvement of the health-related quality of life due to the operation. Odd feeling, numbness and the formation of scar tissue were the main complaints. Partial auricular reconstruction using porous polyethylene combined with an endoscopically harvested temporoparietal fascia flap and autologous skin grafts yields good esthetic results and can significantly increase patient's health-related quality of life. PMID- 24213273 TI - Isolating single stranded DNA using a microfluidic dialysis device. AB - Isolating a particular strand of DNA from a double stranded DNA duplex is an important step in aptamer generation as well as many other biotechnology applications. Here we describe a microfluidic, flow-through, dialysis device for isolating single-stranded DNA (ssDNA) from double-stranded DNA (dsDNA). The device consists of two channels fabricated in polydimethylsiloxane (PDMS) separated by a track etched polycarbonate membrane (800 nm pore size). To isolate ssDNA, dual-biotin labelled dsDNA was immobilized onto streptavidin-coated polystyrene beads. Alkaline treatment was used to denature dsDNA, releasing the non-biotinylated ssDNA. In the flow-through dialysis device the liberated ssDNA was able to cross the membrane and was collected in an outlet channel. The complementary sequence bound to the bead was unable to cross the membrane and was directed to a waste channel. The effect of NaOH concentration and flow rate on purity and yield were compared. >95% ssDNA purity was achieved at 25 mM NaOH. However, lower flow rates were necessary to achieve ssDNA yields approaching the 50% theoretical maximum of the concurrent-flow device. Under optimized conditions the microfluidic isolation achieved even higher purity ssDNA than analogous manual procedures. PMID- 24213275 TI - When is re-irradiation in head and neck squamous cell carcinoma not indicated? PMID- 24213276 TI - Verrucous carcinoma: a retrospective diagnosis in three historic patients. PMID- 24213277 TI - Serologic biomarkers of Epstein-Barr virus correlate with TNM classification according to the seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma. AB - This study aimed to investigate the association between Epstein-Barr virus (EBV) related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation. PMID- 24213278 TI - The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation. AB - The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3% (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2% (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer. PMID- 24213279 TI - Carbon nanotubes: Captured on camera. PMID- 24213280 TI - High-throughput optical imaging and spectroscopy of individual carbon nanotubes in devices. AB - Single-walled carbon nanotubes are uniquely identified by a pair of chirality indices (n,m), which dictate the physical structures and electronic properties of each species. Carbon nanotube research is currently facing two outstanding challenges: achieving chirality-controlled growth and understanding chirality dependent device physics. Addressing these challenges requires, respectively, high-throughput determination of the nanotube chirality distribution on growth substrates and in situ characterization of the nanotube electronic structure in operating devices. Direct optical imaging and spectroscopy techniques are well suited for both goals, but their implementation at the single nanotube level has remained a challenge due to the small nanotube signal and unavoidable environment background. Here, we report high-throughput real-time optical imaging and broadband in situ spectroscopy of individual carbon nanotubes on various substrates and in field-effect transistor devices using polarization-based microscopy combined with supercontinuum laser illumination. Our technique enables the complete chirality profiling of hundreds of individual carbon nanotubes, both semiconducting and metallic, on a growth substrate. In devices, we observe that high-order nanotube optical resonances are dramatically broadened by electrostatic doping, an unexpected behaviour that points to strong interband electron-electron scattering processes that could dominate ultrafast dynamics of excited states in carbon nanotubes. PMID- 24213281 TI - Transport and self-organization across different length scales powered by motor proteins and programmed by DNA. AB - In eukaryotic cells, cargo is transported on self-organized networks of microtubule trackways by kinesin and dynein motor proteins. Synthetic microtubule networks have previously been assembled in vitro, and microtubules have been used as shuttles to carry cargoes on lithographically defined tracks consisting of surface-bound kinesin motors. Here, we show that molecular signals can be used to program both the architecture and the operation of a self-organized transport system that is based on kinesin and microtubules and spans three orders of magnitude in length scale. A single motor protein, dimeric kinesin-1, is conjugated to various DNA nanostructures to accomplish different tasks. Instructions encoded into the DNA sequences are used to direct the assembly of a polar array of microtubules and can be used to control the loading, active concentration and unloading of cargo on this track network, or to trigger the disassembly of the network. PMID- 24213282 TI - Enhanced shoot regeneration from Brassica campestris by silver nitrate. AB - The morphogenetic response of Brassica campestris genotype R500 to inhibitors of ethylene biosynthesis and action was investigated. A medium containing 1.0 mg.l( 1) NAA, 2.0 mg.l(-1) BAP, and 30 or 60 MUM AgNO3 significantly enhanced both the percentage shoot regeneration and the number of shoots per cotyledon expiant. Although callus proliferation occurred on hypocotyl segments, no shoots were formed in response to AgNO3 with expiants older than five days. Cotyledons older than six days formed shoots only with AgNO3. Cobalt chloride at 20 and 30 MUM increased cotyledon shoot regeneration but was inferior to AgNO3. Hypocotyl segments were unresponsive. Salicylic acid at 25 and 50 MUM prevented both shoot regeneration and callusing without any obvious toxic effects. Removal of expiants from AgNO3 after 12 days did not alter the percentage of shoot regeneration but increased the number of shoots per expiant. This response was dependent on the level of BAP. Percentage shoot regeneration and number of shoots per cotyledon explant were not affected by removal of CoCl2. These results indicate that the poor regenerative capacity of this genotype may be related to ethylene biosynthesis or metabolism. PMID- 24213283 TI - In vitro culture of coconut endosperm: callus induction and its fatty acids. AB - Successful induction of callus from coconut endosperm was achieved by using the tissue situated near the micropylar end of a young fruit. For initiation of callus, a high concentration of auxin (20 to 100 ppm) was added to the basal medium containing activated charcoal. Subcultured callus showed a 40-fold increase during culture of three months. Based on the analysis of fatty acid composition, the maturation of endosperm was characterized by an increase in short chain fatty acids (C8, C10, C12, C14)and a decrease in long chain fatty acids (C16, C18: 1, C18: 2). In developing endosperms, proportion of short chain fatty acids was higher in lipids of the antipodal than those of other regions. In the final stage of maturation, around 82% of total fatty acids was short chain fatty acids, while the proportion of long chain fatty acids decreased up to 16%. The fatty acid composition of callus subcultured for six months was comparable to that of the immature endosperm. Lipids were accumulated in callus as globular bodies. PMID- 24213284 TI - Simple dehydration treatment promotes plantlet regeneration of rice (Oryza sativa L.) callus. AB - To increase plantlet regeneration frequency, rice callus was dehydrated in a Petri dish with a single layer of filter paper prior to transfer to the regeneration medium. With a 24 h dehydration treatment, the regeneration frequency was increased to 47 %, while the regeneration frequency of the untreated control was less than 5 %. This relatively simple method provides an alternative method for improving the regeneration frequency of rice callus. PMID- 24213285 TI - Differentiation of somatic embryos from protoplasts isolated from embryogenic suspension cultures of Abies alba L. AB - Embryogenic suspension cultures of Abies alba were established using an embryogenic suspensor mass culture originating from the zygotic embryo in immature seed explants (Schuller et al. 1989). Protoplasts were isolated from the suspension material. The protoplasts were immobilized in alginate layers in order to follow the development of single protoplasts. During the first days of protoplast culture a modified Kao and Michayluk (1975) medium proved to be necessary for subsequent divisions. The formation of proembryos succeeded within 2-3 weeks when subcultured with a modified Schenk and Hildebrandt (1972) liquid medium. Light, enhanced sugar concentration, and the addition of abscisic acid led to the formation of slightly green "torpedo"-shaped somatic embryos after 6-8 weeks from protoplast isolation. PMID- 24213286 TI - Agrobacterium-mediated transformation of tomatillo (Physalis ixocarpa) and tissue specific and developmental expression of the CaMV 35S promoter in transgenic tomatillo plants. AB - A protocol for the Agrobacterium-mediated transformation of tomatillo was developed. Up to 40 transgenic plants could be obtained in experiments using 60 cotyledon expiants. The transformed nature of the regenerated plants was confirmed by NPT II and Southern blot hybridization analysis. Using the b glucuronidase system the tissue specific and developmental patterns of expression of the Cauliflower Mosaic Virus 35S promoter were determined in transgenic tomatillo plants. It was found that this promoter is developmentally regulated during fruit and seed formation. PMID- 24213287 TI - First evidence of somatic embryogenesis from needles of 1-year-old Picea abies plants. AB - Somatic embryogenesis was obtained from hypocotyls and cotyledons of one month old plantlets of Picea abies. Embryogenic yield was higher with expiants from somatic embryo-derived plantlets (80 %) than with plantlets issued from zygotic embryos (10 %). This report also describes production of embryogenic calli from needles of 14 month old somatic embryo-derived plants cultivated in greenhouse. The influence of the physiological status and genotype of the mother plant on somatic embryogenic potential is discussed. PMID- 24213288 TI - Electroporation and PEG delivery of DNA into maize microspores. AB - The ability to deliver and detect reporter gene activity in maize microspores was tested. Tested expression vectors contained the chloramphenicol acetyl transferase (CAT) gene and one of the following promoter-intron combinations: 1) cauliflower mosaic virus (CaMV 35S), 2) CaMV 35S + maize alcohol dehydrogenase 1 intron 6 (Adh1-I6), 3) maize alcohol dehydrogenase 1 + intron 1 (Adh1-I1), or 4) maize ubiquitin 1 + intron 1 (Ubiq 1-I1) promoter + intron. The expression vectors were delivered into maize microspores using electroporation or polyethylene glycol (PEG). Both methods were effective for delivering free DNA into microspores. Although all four promoters were active in maize protoplasts, only two promoters were active in maize microspores. The CaMV 35S and the Adh1 promoters did not promote gene expression in maize microspore. The CaMV 35S + Adh1-I6 and Ubiq1-I1 promoters produced high levels of CAT activity in maize microspores. PMID- 24213289 TI - Propagation of banana through encapsulated shoot tips. AB - Plants were regenerated from encapsulated shoot tips of banana. Shoot tips (ca 4 mm) isolated from multiple shoot cultures of banana cv. Basrai were encapsulated in 3% sodium alginate containing different gel matrices. The encapsulated shoot tips regenerated in vitro on different substrates. Use of White's medium resulted in 100% conversion of encapsulated shoot tips into plantlets. The plantlets were successfully established in soil. PMID- 24213290 TI - Genotype-specific heat shock proteins in two maize inbreds. AB - Leaf blade tissue of maize inbred lines B73 and Mo17 was analyzed for intraspecific genetic variability in the heat shock response. The maize inbreds were characterized for acquired thermal tolerance and patterns of heat shock protein synthesis. The leakage conductivity assay of membrane stability during stress indicated that Mol7 possesses greater potential than B73 to acquire thermal tolerance. Poly(A)(+) RNA, extracted from leaf blades, was translated in vitro in the presence of (35)S-methionine and the translation products separated by twodimensional gel electrophoresis. Major genotypic differences were observed in the translation products. Mo 17 synthesized twelve unique heat shock proteins in the 15-18 kD range, but B73 synthesized only three unique heat shock proteins in the same range. DNA polymorphisms were observed between the maize lines using (32)P labeled heat shock protein gene probes. PMID- 24213291 TI - Agrobacterium tumefaciens-mediated transformation of safflower (Carthamus tinctorius L.) cv. 'Centennial'. AB - Efficient callus formation was achieved from cotyledon, stem, and leaf expiants of the domestic safflower cultivar 'Centennial' on MS salts medium containing 1 mg/L BAP and 1 mg/L NAA. Shoot buds were regenerated from 26% of leaf-derived calli on callus induction medium, although attempts to root regenerated shoots were not successful. 'Centennial' expiants inoculated with Agrobacterium tumefaciens containing NPT II and GUS genes produced kanamycin-resistant calli from which buds were regenerated. Transformation and stable integration of transgenes was confirmed by GUS assay and DNA hybridization in kanamycin resistant calli, and GUS assay in regenerated shoots. PMID- 24213292 TI - Regeneration of herbicide resistant transgenic rice plants following microprojectile-mediated transformation of suspension culture cells. AB - Suspension cells of Oryza sativa L. (rice) were transformed, by microprojectile bombardment, with plasmids carrying the coding region of the Streptomyces hygroscopicus phosphinothricin acetyl transferase (PAT) gene (bar) under the control of either the 5' region of the rice actin 1 gene (Act1) or the cauliflower mosaic virus (CaMV) 35S promoter. Subsequently regenerated plants display detectable PAT activity and are resistant to BASTA(TM), a phosphinothricin (PPT)-based herbicide. DNA gel blot analyses showed that PPT resistant rice plants contain a bar-hybridizing restriction fragment of the expected size. This report shows that expression of the bar gene in transgenic rice plants confers resistance to PPT-based herbicide by suppressing an increase of ammonia in plants after spraying with the herbicide. PMID- 24213293 TI - Bioproduction of neohesperidin and naringin in callus cultures of Citrus aurantium. AB - The accumulation of both neohesperidin and naringin as major flavonoids in callus cultures of bitter orange (Citrus aurantium) was demonstrated using high performance liquid chromatography with a diode-array detector. The identity of both compounds was confirmed by their corresponding nuclear magnetic resonance spectra. The levels of neohesperidin are higher than those of naringin in callus culture, as they are in immature fruit, and high concentrations of both are found in young tissues such as immature fruits and the outer zone of calli. PMID- 24213295 TI - Fish skin bacteria: Colonial and cellular hydrophobicity. AB - Bacteria were desorbed from the skin of healthy, fast-swimming fish by several procedures, including brief exposure to sonic oscillation and treatment with nontoxic surface active agents. The surface properties of these bacteria were studied by measuring their adhesion to hexadecane, as well as by a newly developed, simple method for studying the hydrophobicity of bacterial lawns. This method, referred to as the "Direction of Spreading" (DOS) method, consists of recording the direction to which a water drop spreads when introduced at the border between bacterial lawns and other surfaces. Of the 13 fish skin isolates examined, two strains were as hydrophobic as polystyrene by the DOS method. Suspended cells of one of these strains adhered strongly to hexadecane (84%), whereas cells of the other strain adhered poorly (13%). Another strain which was almost as hydrophobic as polystyrene by the DOS method did not adhere to hexadecane at all. Similarly, lawns of three other strains were more hydrophobic than glass by the DOS method, but cell suspensions prepared from these colonies showed little or no adhesion to hexadecane. The high colonial but relatively low cellular hydrophobicity could be due to a hydrophobic slime that is removed during the suspension and washing procedures. The possibility that specific bacteria assist in fish locomotion by changing the surface properties of the fish skin and by producing drag-reducing polymers is discussed. PMID- 24213294 TI - Review: Microbial colonization of prosthetic devices. AB - CONCLUSION: The threat of bacterial colonization and biofilm formation poses the most important limitation on the use and development of prosthetic devices in human medicine. Data from the literature suggest that microbial adherence effected by the glycocalyx is a fundamental factor in sepsis involving biomaterials and that it may explain the resistance of such infections to host defense mechanisms and to antibiotherapy. A full appreciation of the existence and the consequences of the biofilm mode of bacterial growth is required so that we can both prevent and eliminate these protected microbial reservoirs. PMID- 24213296 TI - Grazing of attached bacteria by heterotrophic microflagellates. AB - Four species of heterotrophic microflagellates were examined for their ability to graze attached and unattached bacteria. The species tested displayed pronounced differences in their ability to graze the bacteriumPseudomonas halodurans attached to chitin particles. Two species of microflagellates (Monas andCryptobia sp.) efficiently grazed unattached bacteria but showed little or no ability to graze attached or aggregated cells. In contrast,Rhynchomonas nasuta andBodo sp. showed marked preferences for attached and aggregated bacteria and a limited ability to graze unattached cells. The density of attached bacteria was reduced by an order of magnitude due to grazing byBodo andR. nasuta, even though the density of unattached bacteria was ~5-90* the density of attached cells. The maximum densities attained by microflagellates in the cultures were related to the density of unattached bacteria forMonas andCryptobia but not forBodo andR. nasuta. Growth of the latter two species appeared to be related to the density of attached or aggregated bacteria. Based on the results of these experiments, it is concluded that the pelagic existence of microflagellates that graze attached bacteria may be strongly linked to the distribution of suspended particles and their associated bacteria. In addition, the removal of attached bacteria by microflagellates can significantly affect the density of bacteria attached to particles in the plankton. This activity may have important implications for the controversy concerning the relative importance of attached and free-living bacteria in the plankton. PMID- 24213297 TI - Negative staining of freshwater bacterioneuston sampled directly with electron microscope specimen support grids. AB - A technique for observation of surface microlayer bacteria (bacterioneuston) is described, utilizing direct sampling of the air-water interface with carbon stabilized electron microscope specimen support grids, followed by negative staining and transmission electron microscopy. The method resulted in excellent preservation of forms of microcolonial association, regular surface arrays, surface appendages, and prosthecae in the bacterioneuston of a freshwater pond. PMID- 24213298 TI - Kinetics of alkaline phosphatase activity and phosphorus availability for phytoplankton and bacterioplankton in lake plu?see (North German Eutrophic Lake). AB - Annual studies of kinetics of alkaline phosphatase (APA) activity and phosphorus availability for microplankton in the photic zone of an eutrophic lake are reported. The total APA activity of microplankton varied strongly. Vmax was highest during summer P depletion, and in autumn and winter total APA activity was low. The total APA specific activity of the microplankton was also highest (average 3.55 pmole PO4 (3-) ng ATP(-1) min(-1)) when ambient orthophosphate concentrations were very low. Both Vmax and specific APA activity were not dependent on the biomass of microplankton; they were strongly affected by P available for microplankton. A differential filtration technique was used for separation of microplankton into two size classes, i.e., algal, larger than 3MUm, and bacterial fraction with size 0.2-3.0MUm. The algal size fraction had lower specific APA activity (average 1.224 pmole PO4 (3-) ng ATP(-1) min(-1)) and higher KM values (38.8MUmole * liter(-1)) than microorganisms which were smaller than 3MUm (2.011 pmole PO4 (3-) ng ATP(-1) min(-1) and 25.4MUmole liter(-1), respectively). The KM values of free, dissolved APA (36.8MUmole liter(-1)) indicated that free APA was probably released by algae. Phytoplankton were major APA activity producers in the photic zone of the lake from March to November, and their activity constituted, on the average, 48.6% of the total APA activity in the water. Bacteria were the dominant APA activity producers in winter (41.3 44.9%); however, during other periods they contributed significantly (average 21.7%) to total APA activity. When surplus constituted less than 10% of particulate P in seston, phytoplankton produced high specific APA activity, and when surplus P was higher than 15%, the specific APA activity of phytoplankton size fraction rapidly decreased. APA of the bacterial size fraction of the seston was not affected by P concentrations. Orthophosphate was a competitive inhibitor of APA produced by microorganisms of the size fraction larger than 3.0MUm, and increasing concentrations of inorganic phosphate caused an increase in KM values. The hypothetical metabolic-coupling between phytoplankton and bacterioplankton in the phosphorus cycle in conjunction with carbon metabolism in the lake is discussed. PMID- 24213299 TI - Patterns of dark(14)CO 2 incorporation by natural marine phytoplankton communities. AB - The rates of dark(14)CO2 fixation by natural phytoplankton communities growing in eutrophic and oligotrophic waters were studied with short-term in situ experiments. Three aspects were investigated: (1) the time course incorporation of(14)CO2 in darkness, (2) the depth variability in dark(14)CO2 fixation, and (3) the variability in(14)CO2 fixation within a year. The highest dark(14)CO2 incorporation rates were observed during the first interval of incubation (20 min) after which they approached a constant rate with time. The observed differences in dark(14)CO2 fixation rates between populations from different depths were associated with differences in species composition as well as with physiological differences caused by exposure to different illumination conditions prior to their exposure to darkness. Autocorrelation coefficients were computed for the analysis of variability of dark(14)CO2 fixation rates within a year. It was suggested that dark(14)CO2 incorporation might be a periodic phenomenon depending mainly on the productive capacity of the phytoplankton community. PMID- 24213300 TI - Isolation ofNostoc muscorum cyanophages from a domestic sewage. AB - TwoNostoc muscorum cyanophages were isolated from a domestic sewage in Kuwait. N 1L cyanophage had a hexagonal head with a long tail, while N-2S cyanophage was a short-tailed virus. N-1L cyanophage was active at 50 degrees C and at acidic pH, compared with N-2S, which was more heat stable and active at pH 7.0. Seasonal variations in the total number of plaque-forming units ofN. muscorum cyanophages were determined for sewage samples collected at each treatment step. PMID- 24213301 TI - Exploring empowerment in settings: mapping distributions of network power. AB - This paper brings together two trends in the empowerment literature-understanding empowerment in settings and understanding empowerment as relational-by examining what makes settings empowering from a social network perspective. Specifically, extending Neal and Neal's (Am J Community Psychol 48(3/4):157-167, 2011) conception of network power, an empowering setting is defined as one in which (1) actors have existing relationships that allow for the exchange of resources and (2) the distribution of network power among actors in the setting is roughly equal. The paper includes a description of how researchers can examine distributions of network power in settings. Next, this process is illustrated in both an abstract example and using empirical data on early adolescents' peer relationships in urban classrooms. Finally, implications for theory, methods, and intervention related to understanding empowering settings are explored. PMID- 24213302 TI - Influence of paraumbilical vein patency on the portal hemodynamics of patients with cirrhosis. AB - GOALS/BACKGROUND: The aim was to determine the influence of the paraumbilical vein (PUV) patency and its effect on the portal hemodynamics and clinical presentations in cirrhotic patients. STUDY: In this prospective study of 181 cirrhotic patients (101 males, 80 females; aged 62.6+/-11.8 y), the portal hemodynamics were assessed using Doppler ultrasonography. RESULTS: The incidence of patent PUV was 26.0% (47/181). The mean flow volume in the portal trunk, the incidence of a left gastric vein with hepatofugal flow, and the grade of the esophageal varices were significantly higher in the patients with a patent PUV (908.2 mL/min, 70.2%, 9 with none to small, and 27 with medium to large, respectively) than in those without (771.7 mL/min, 48.5%, 57 with none to small, and 48 with medium to large, respectively). The hepatic venous pressure gradient and the wedged hepatic venous pressure (mm H2O) were significantly higher in the former group (268.0+/-89.7 and 389.5+/-99.9, respectively) than in the latter (203.5+/-63.2 and 317.7+/-67.7, respectively). The deterioration of ascites during the 2-year follow-up period was significantly more often in the patients with a patent PUV (4/12, 33.3%) than in those without. The cumulative survival rates at 1, 2, and 3 years were similar between the 2 groups: 92.5%, 92.5%, and 82.4%, respectively, in the former and 90.7%, 83.8%, and 76.3%, respectively, in the latter. CONCLUSIONS: A patent PUV seems to signify pressure-loaded portal hemodynamics in cirrhotic patients. However, it seems to have little effect on their prognoses. PMID- 24213303 TI - Stimulatory effects of sorafenib on human non-small cell lung cancer cells in vitro by regulating MAPK/ERK activation. AB - Sorafenib is an inhibitor of a number of intracellular signaling kinases with antiproliferative, anti-angiogenic and pro-apoptotic effects in tumor cells. Sorafenib has been used in the therapy of advanced renal cell carcinoma. In the present study, using two human non-small cell lung cancer (NSCLC)cell lines, A549 and NCI-H1975, the effects of sorafenib on proliferation, apoptosis and intracellular signaling were systematically characterized. The results revealed that at a low concentration (5 uM) and early time point (6 h), sorafenib is capable of significantly stimulating proliferation of A549 cells, but not NCI H1975 cells. In addition, the comparison of the two cell lines revealed different cell cycle redistribution and apoptotic susceptibility to sorafenib at this concentration and time point. Western blot analysis revealed that sorafenib upregulated the expression of cyclin D1 and cyclin-dependent kinase 2 and downregulated the expression of BAX at this specific point. Furthermore, sorafenib was confirmed to regulate the expression of cyclin D1 and apoptosis associated proteins through the regulation of extracellular signal-regulated kinase 1/2 phosphorylation in A549 cells. These findings suggest that, although sorafenib has the potential for use in the treatment of renal cell carcinoma, this compound may also activate NSCLC cells at a specific time point. PMID- 24213305 TI - Genetic diagnosis of Duchenne and Becker muscular dystrophy using multiplex ligation-dependent probe amplification in Rwandan patients. AB - Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic diagnosis was carried out in six Rwandan patients presenting a phenotype of Duchenne and Becker muscular dystrophies and six asymptomatic female carrier relatives using multiplex ligation-dependent probe amplification (MLPA). Our results revealed deletion of the exons 48-51 in one patient, an inherited deletion of the exons 8-21 in two brothers and a de novo deletion of the exons 46-50 in the fourth patient. No copy number variation was found in two patients. Only one female carrier presented exon deletion in the DMD gene. This is the first cohort of genetic analysis in Rwandan patients affected by Duchenne and Becker muscular dystrophies. This report confirmed that MLPA assay can be easily implemented in low-income countries. PMID- 24213304 TI - Leptin-stimulated KATP channel trafficking: a new paradigm for beta-cell stimulus secretion coupling? AB - Insulin secretion from pancreatic beta-cells is initiated by the closure of ATP sensitive K+ channels (KATP) in response to high concentrations of glucose, and this action of glucose is counteracted by the hormone leptin, an adipokine that signals through the Ob-Rb receptor to increase KATP channel activity. Despite intensive investigations, the molecular basis for KATP channel regulation remains uncertain, particularly from the standpoint of whether fluctuations in plasma membrane KATP channel content underlie alterations of KATP channel activity in response to glucose or leptin. Surprisingly, newly published findings reveal that leptin stimulates AMP-activated protein kinase (AMPK) in order to promote trafficking of KATP channels from cytosolic vesicles to the plasma membrane of beta-cells. This action of leptin is mimicked by low concentrations of glucose that also activate AMPK and that inhibit insulin secretion. Thus, a new paradigm for beta-cell stimulus-secretion coupling is suggested in which leptin exerts a tonic inhibitory effect on beta-cell excitability by virtue of its ability to increase plasma membrane KATP channel density and whole-cell KATP channel current. One important issue that remains unresolved is whether high concentrations of glucose suppress AMPK activity in order to shift the balance of membrane cycling so that KATP channel endocytosis predominates over vesicular KATP channel insertion into the plasma membrane. If so, high concentrations of glucose might transiently reduce KATP channel density/current, thereby favoring beta-cell depolarization and insulin secretion. Such an AMPK-dependent action of glucose would complement its established ability to generate an increase of ATP/ADP concentration ratio that directly closes KATP channels in the plasma membrane. PMID- 24213306 TI - Objectively measured habitual physical activity and sedentary behaviour in obese and non-obese Malaysian children. AB - The present study examined objectively measured physical activity in Malaysian children and compared the differences in physical levels between obese and healthy weight children. Eighty-six obese children were matched for age and sex with 86 healthy weight children with median age 9.5 years. Habitual physical activity and sedentary behaviour were measured over 5 days using Actigraph accelerometers. Time spent sedentary was significantly higher in the obese group (90% vs. 86% of daytime; p = 0.001). Moderate-to-vigorous-intensity physical activity was significantly higher in the healthy weight group (1.2 vs. 0.7% of daytime, p < 0.001). In both healthy weight and obese children, physical activity levels were exceptionally low, although moderate-to-vigorous-intensity physical activity was significantly lower in the obese group than the healthy weight group. Efforts to prevent and treat obesity in Malaysian children will need a substantial focus on the promotion of reductions in sedentary behaviour and increases in physical activity. PMID- 24213307 TI - Acute presentation of thrombocytopaenia in systemic lupus erythematosus is associated with a high mortality in South Africa. AB - The objective of this study was to determine the pattern of presentation, response to treatment, and outcome in patients with systemic lupus erythematosus (SLE) and thrombocytopaenia (TCP). A retrospective review of the records of patients with SLE and TCP and a matched control group of SLE patients without TCP, seen in the rheumatology department in Durban, South Africa, was performed. The demographic data, clinical findings, laboratory findings, treatment and outcome were recorded. There were 54 patients and an equal number of controls. They comprised 30 Indians and 24 African Blacks, median age of 33 years and female to male ratio 5.8:1. A group of eight patients who initially presented with idiopathic thrombocytopaenic purpura (ITP) and subsequently developed SLE were analysed separately. An acute presentation was noted in 31 patients (57%). Patients with an acute presentation had an increased prevalence of renal disease (77% vs 43.5%; p=0.01) and an increased number of deaths (38.7% vs 4.4%; p=0.004). The majority of patients responded to corticosteroids (68.5%) and splenectomy. There was an increased prevalence of renal disease (p=0.03) and deaths (p=0.004) among patients with TCP. The majority of deaths had an acute presentation ((12/13; 92.3%) (p=0.004)), and were due to infection and active lupus. TCP with an acute presentation is associated with a high mortality and predicts survival in SLE. PMID- 24213308 TI - Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A. AB - Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term. PMID- 24213309 TI - Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. AB - BACKGROUND: Brown adipose tissue (BAT) is involved in the regulation of whole body energy expenditure and adiposity. Some clinical studies have reported an association between BAT and blood glucose in humans. OBJECTIVE: To examine the impact of BAT on glucose metabolism, independent of that of body fatness, age and sex in healthy adult humans. METHODS: Two hundred and sixty healthy volunteers (184 males and 76 females, 20-72 years old) underwent fluorodeoxyglucose-positron emission tomography and computed tomography after 2 h of cold exposure to assess maximal BAT activity. Blood parameters including glucose, HbA1c and low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol were measured by conventional methods, and body fatness was estimated from body mass index (BMI), body fat mass and abdominal fat area. The impact of BAT on body fatness and blood parameters was determined by logistic regression with the use of univariate and multivariate models. RESULTS: Cold-activated BAT was detected in 125 (48%) out of 260 subjects. When compared with subjects without detectable BAT, those with detectable BAT were younger and showed lower adiposity-related parameters such as the BMI, body fat mass and abdominal fat area. Although blood parameters were within the normal range in the two subject groups, HbA1c, total cholesterol and LDL-cholesterol were significantly lower in the BAT-positive group. Blood glucose also tended to be lower in the BAT-positive group. Logistic regression demonstrated that BAT, in addition to age and sex, was independently associated with BMI, body fat mass, and abdominal visceral and subcutaneous fat areas. For blood parameters, multivariate analysis after adjustment for age, sex and body fatness revealed that BAT was a significantly independent determinant of glucose and HbA1c. CONCLUSION: BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans. PMID- 24213312 TI - Superficial EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion: a new variant of Ewing-like tumors with locoregional lymph node metastasis. AB - The present study describes a new case of EWSR1-negative undifferentiated sarcoma with CIC/DUX4 gene fusion. This case is similar to tumors described as primitive undifferentiated round cell sarcomas that occur mainly in the trunk and display an aggressive behavior. To our knowledge, this is the first report of such a tumor presenting locoregional lymph node metastasis. In view of previous studies that prove the existence of a particular variant of undifferentiated sarcoma with Ewing-like morphology and CIC/DUX-4 gene fusion, a search for this gene fusion in all undifferentiated round cell sarcomas should be considered if a conclusive diagnosis cannot be reached following other conventional studies. Although additional cases with more extensive follow-up studies are needed, we believe that EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion should be added to the list of new sarcoma variants with the possibility of lymph node metastasis. PMID- 24213310 TI - Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery? AB - The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of beta-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals. PMID- 24213313 TI - Micronutrient Synergy in the Fight against Hepatocellular Carcinoma. AB - The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13 acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression, such as proliferation, invasion and metastasis, and by inducing apoptosis. PMID- 24213314 TI - Remodeling of tumor stroma and response to therapy. AB - Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy. PMID- 24213316 TI - External beam radiotherapy of recurrent glioma: radiation tolerance of the human brain. AB - Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative). Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials. PMID- 24213315 TI - A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed. PMID- 24213317 TI - The dynamics of developmental and tumor angiogenesis-a comparison. AB - The blood vasculature in cancers has been the subject of intense interest during the past four decades. Since the original ideas of targeting angiogenesis to treat cancer were proposed in the 1970s, it has become evident that more knowledge about the role of vessels in tumor biology is needed to fully take advantage of such strategies. The vasculature serves the surrounding tissue in a multitude of ways that all must be taken into consideration in therapeutic manipulation. Aspects of delivery of conventional cytostatic drugs, induction of hypoxia affecting treatment by radiotherapy, changes in tumor cell metabolism, vascular leak and trafficking of leukocytes are affected by interventions on vascular function. Many tumors constitute a highly interchangeable milieu undergoing proliferation, apoptosis, and necrosis with abundance of growth factors, enzymes and metabolites. These aspects are reflected by the abnormal tortuous, leaky vascular bed with detached mural cells (pericytes). The vascular bed of tumors is known to be unstable and undergoing remodeling, but it is not until recently that this has been dynamically demonstrated at high resolution, facilitated by technical advances in intravital microscopy. In this review we discuss developmental genetic loss-of-function experiments in the light of tumor angiogenesis. We find this a valid comparison since many studies phenocopy the vasculature in development and tumors. PMID- 24213318 TI - Immune response to sipuleucel-T in prostate cancer. AB - Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients' own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for immunotherapy, patient selection and best sequencing with other prostate cancer therapies remain to be determined. A better understanding of immune response may help address these issues. PMID- 24213320 TI - T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma. AB - Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy. PMID- 24213319 TI - Radical decisions in cancer: redox control of cell growth and death. AB - Free radicals play a key role in many physiological decisions in cells. Since free radicals are toxic to cellular components, it is known that they cause DNA damage, contribute to DNA instability and mutation and thus favor carcinogenesis. However, nowadays it is assumed that free radicals play a further complex role in cancer. Low levels of free radicals and steady state levels of antioxidant enzymes are responsible for the fine tuning of redox status inside cells. A change in redox state is a way to modify the physiological status of the cell, in fact, a more reduced status is found in resting cells while a more oxidative status is associated with proliferative cells. The mechanisms by which redox status can change the proliferative activity of cancer cells are related to transcriptional and posttranscriptional modifications of proteins that play a critical role in cell cycle control. Since cancer cells show higher levels of free radicals compared with their normal counterparts, it is believed that the anti-oxidative stress mechanism is also increased in cancer cells. In fact, the levels of some of the most important antioxidant enzymes are elevated in advanced status of some types of tumors. Anti-cancer treatment is compromised by survival mechanisms in cancer cells and collateral damage in normal non-pathological tissues. Though some resistance mechanisms have been described, they do not yet explain why treatment of cancer fails in several tumors. Given that some antitumoral treatments are based on the generation of free radicals, we will discuss in this review the possible role of antioxidant enzymes in the survival mechanism in cancer cells and then, its participation in the failure of cancer treatments. PMID- 24213322 TI - Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma. AB - Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is almost never curable with the current standard treatment consisting of surgical resection, irradiation and temozolomide. The prognosis remains poor despite undisputable advances in the understanding of this tumor's molecular biology and pathophysiology, which unfortunately has so far failed to translate into a meaningful clinical benefit. Dysregulation and a resulting prominent pathophysiological role of the epidermal growth factor receptor (EGFR) have been identified in several different malignant tumor entities, GBM among them. The EGFR is overexpressed in about 40% of GBM cases, and half of these coexpress a mutant, constitutively activated subtype, EGFRvIII. Unfortunately, recent trials studying with therapeutic approaches targeted against the EGFR and EGFRvIII have failed to meet expectations, with only a minority of patients responding despite evidence of good in vitro and rodent model activity. Having potentially high relevance within this context, epithelial to mesenchymal transition (EMT) is a phenomenon associated with early stages of carcinogenesis, cancer invasion and recurrence. During EMT, epithelial cells lose many of their epithelial characteristics, prominently E-cadherin expression, and acquire properties that are typical for mesenchymal cells such as the expression of vimentin. Epithelial to mesenchymal transition has been specifically demonstrated in GBM. In this review, we summarize the evidence that EMT may precipitate GBM resistance to EGFR targeted therapy, and may thus be among the principal factors contributing to the clinical failure of targeted therapy against EGFR and EGFRvIII. PMID- 24213321 TI - Gastroenteropancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1. AB - We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present. PMID- 24213323 TI - The stroma-a key regulator in prostate function and malignancy. AB - Prostate cancer is a very common and highly unpredictable form of cancer. Whereas many prostate cancers are slow growing and could be left without treatment, others are very aggressive. Additionally, today there is no curative treatment for prostate cancer patients with local or distant metastasis. Identification of new, improved prognostic and diagnostic biomarkers for prostate cancer and the finding of better treatment strategies for metastatic prostate cancer is therefore highly warranted. Interactions between epithelium and stroma are known to be important already during prostate development and this interplay is critical also in development, progression of primary tumors and growth of metastases. It is therefore reasonable to expect that future biomarkers and therapeutic targets can be identified in the prostate tumor and metastasis stroma and this possibility should be further explored. PMID- 24213324 TI - Potentiality and boundaries of use of sorafenib in patients with hepatocellular carcinoma: awaiting the results of ongoing clinical trials. AB - No systemic therapy had been proven effective in patients with advanced hepatocellular carcinoma (HCC) until 2007, when a large randomized trial with sorafenib demonstrated a clinically relevant prolongation of survival. Currently, sorafenib represents standard treatment for patients with advanced HCC and well preserved liver function, whilst the evidence about its effectiveness in patients with more severe liver impairment is less robust. A randomized trial to demonstrate the efficacy of sorafenib in Child-Pugh B patients with advanced HCC is currently ongoing. In the meantime, several trials are testing the role of sorafenib in early HCC (as adjuvant treatment after potentially curative loco regional therapies) and in intermediate stage (exploring different modalities of integration of sorafenib with trans-arterial chemo-embolization). The results of all these trials will better define the potentiality and the boundaries of use of sorafenib in HCC patients. PMID- 24213325 TI - An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications. AB - In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), a/beta and radiosensitivity a, were estimated. Other radiobiological models: EUD, BED, TCP, etc., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined a/beta, a and Td are a/beta = 8.1 +/- 4.1 Gy, a = 0.22 +/- 0.08 Gy-1, Td = 4.0 +/- 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, i.e., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment. PMID- 24213327 TI - Minimal residual disease as a predictive factor for relapse after allogeneic hematopoietic stem cell transplant in adult patients with acute myeloid leukemia in first and second complete remission. AB - Allogeneic hematopoietic stem cell transplantation (allo-SCT) is potentially curative for patients with high-risk leukemia, but disease recurrence remains the leading cause of treatment failure. Our objective was to determine the impact of minimal residual disease (MRD) by any technique in adult patients with acute myeloid leukemia (AML) in morphologic first and second complete remission undergoing allo-SCT. Fifty nine patients were eligible for the study of 160 patients transplanted over ten years. For the MRD assessment we used multiparametric flow cytometry, cytogenetics and fluorescent in situ hybridization; 19 patients (32.2%) were identified as MRD positive. Patients with MRD had a consistently worse outcome over those without MRD, with 3-years leukemia-free survival (LFS) of 15.8% vs. 62.4% and overall survival (OS) of 17.5% vs. 62.3%. Relapse rate was significantly higher in MRD-positive patients; 3 years relapse rate in MRD-positive patients was 57.9% vs. 15.1% in MRD-negative patients. Detection of MRD in complete remission was associated with increased overall mortality (HR = 3.3; 95% CI: 1.45-7.57; p = 0.0044) and relapse (HR = 5.26; 95% CI: 2.0-14.0; p = 0.001), even after controlling for other risk factors. Our study showed that for patients in morphologic complete remission the presence of MRD predicts for significantly increased risk of relapse and reduced LFS and OS. PMID- 24213326 TI - Substantially modified ratios of effector to regulatory T cells during chemotherapy in ovarian cancer patients return to pre-treatment levels at completion: implications for immunotherapy. AB - Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25hiFoxp3+CD127-CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being "re set" to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients. PMID- 24213328 TI - The sex ratio of full and half siblings of people diagnosed with an autism spectrum disorder: a Danish Nationwide Register Study. AB - In the extreme male brain theory of autism sex steroid hormones are hypothesized to influence brain development and to mediate sex differences in developmental psychopathology. Within this scope we examined the sex ratio (proportion of males) in siblings of individuals diagnosed with autism spectrum disorders (ASD). We did a nationwide, register based cohort study of the sex ratio in 17,380 siblings of the 10,297 patients diagnosed with ASD at age 17 years and younger and registered in the nationwide Danish Psychiatric Central Register between 1994 and 2012. Among the 17,380 siblings 8,828 were males and 8,552 females. This yields a sex ratio of 0.508, which is not different from the Danish live birth sex ratio of 0.513 during the relevant years (P = 0.18). Overall, our findings provide no support for the hypothesis that there are relatively more males among the siblings of people with ASD. Accordingly, our results do not give support to the extreme male brain theory of autism. PMID- 24213330 TI - High resolution RFLP map around the root knot nematode resistance gene (Mi) in tomato. AB - In the 1940's the root-knot nematode resistance gene (Mi) was introgressed into the cultivated tomato from the wild species, L. peruvianum, and today it provides the only form of genetic resistance against this pathogen. We report here the construction of a high resolution RFLP map around the Mi gene that may aid in the future cloning of this gene via chromosome walking. The map covers the most distal nine map units of chromosome 6 and contains the Mi gene, nine RFLP markers, and one isozyme marker (Aps-1). Based on the analysis of more than 1,000 F2 plants from four crosses, we were able to pinpoint the Mi gene to the interval between two of these markers - GP79 and Aps-1. In crosses containing the Mi gene, this interval is suppressed in recombination and is estimated to be 0.4 cM in length. In contrast, for a cross not containing Mi, the estimated map distance is approximately 5 times greater (ca. 2 cM).Using RFLP markers around Mi as probes, it was possible to classify nematode resistant tomato varieties into three types based on the amount of linked peruvianum DNA still present. Two of these types (representing the majority of the varieties tested) were found to still contain more than 5 cM of peruvianum chromosome - a result that may explain some of the negative effects (e.g. fruit cracking) associated with nematode resistance. The third type (represented by a single variety) is predicted to carry a very small segment of peruvianum DNA (<2 cM) and may be useful in the identification of additional markers close to Mi and in the orientation of clones during a chromosome walk to clone the gene. PMID- 24213329 TI - Acute kidney injury after transcatheter aortic valve implantation with self expanding CoreValve prosthesis: results from a large multicentre Italian research project. AB - AIMS: Transcatheter aortic valve implantation (TAVI) can be associated with varying degrees of new renal impairment. The aim of this multicentre analysis was to determine the impact and predictors of periprocedural acute kidney injury (AKI) on prognosis after TAVI. METHODS AND RESULTS: From the ClinicalService (a nation-based data repository and medical care project) dataset, 1,157 patients with severe aortic stenosis treated with the third-generation CoreValve prosthesis in seven Italian sites, and with creatinine data available at baseline and during the post-TAVI in-hospital course, were included in this analysis. All outcomes were defined according to the VARC criteria. Overall, AKI occurred in 231 (20.0%): 15.4% stage 1, 2.7% stage 2, and 1.9% stage 3. Compared to patients without AKI, patients who suffered post-procedural AKI had significantly higher three-year all-cause mortality (31% vs. 12%; adjusted HR: 2.09; 95% CI: 1.52 2.87, p<0.001) and cardiovascular mortality (14% vs. 6%; adjusted HR: 2.28; 95% CI: 1.41-3.71, p=0.001). No significant differences in terms of stroke, spontaneous MI, and bleeding were reported. Female gender (adjusted OR: 1.37, 95% CI: 1.01-1.87; p=0.045), baseline renal insufficiency (adjusted OR: 11.02, 95% CI: 5.12-23.73; p<0.001), general anaesthesia (adjusted OR: 1.37, 95% CI: 1.00 1.87; p=0.050), and transfusion >=3 red blood cell (RBC) units within 72 hrs from TAVI (adjusted OR: 1.65, 95% CI: 1.02-2.68; p=0.041) were found to be independent predictors of AKI. CONCLUSIONS: Acute kidney injury is a frequent complication and significantly impacts on both early and long-term TAVI survival. Females, subjects with impaired renal function at baseline, patients undergoing TAVI under general anaesthesia, and patients receiving >=3 RBC units after the procedure should be considered populations at high risk for the development of AKI after TAVI. PMID- 24213331 TI - Isolation and characterization of wheat-rye recombinants involving chromosome arm 1DS of wheat. AB - The introgression of genetic material from alien species is assuming increased importance in wheat breeding programs. One example is the translocation of the short arm of rye chromosome 1 (1RS) onto homoeologous wheat chromosomes, which confers disease resistance and increased yield on wheat. However, this translocation is also associated with dough quality defects. To break the linkage between the desirable agronomic traits and poor dough quality, recombination has been induced between 1RS and the homoeologous wheat arm IDS. Seven new recombinants were isolated, with five being similar to those reported earlier and two havina new type of structure. All available recombinantsw ere characterized with DNA probes for the loci Nor-R1, 5SDna-R1, and Tel-R1. Also, the amount of rye chromatin present was quantified with a dispersed rye-specific repetitive DNA sequence in quantitative dot blots. Furthermore, the wheat-rye recombinants were used as a mapping tool to assign two RFLP markers to specific regions on chromosome arms 1DS and 1RS of wheat and rye, respectively. PMID- 24213332 TI - Cytological and molecular observations on Solanum phureja-induced dihaploid potatoes. AB - Seventeen potato dihaploids, produced by pollinating the tetraploid (2n = 48) cv 'Pentland Crown' with pollen from Solanum phureja (2n = 24) dihaploid inducer clones, were studied. Since dihaploids are thought to develop parthenogenetically from unfertilized ovules they were expected to be euploid (2n = 24), but somatic chromosome counts showed that 15 of the 17 dihaploids were aneusomatic. Ten of the clones were predominantly diploid (2n = 24) with a proportion of hyperploid cells that contained 25 or 26 chromosomes. Five of the dihaploids contained variable numbers of triploid cells (2n = 36). RFLP analysis was used to determine whether the additional chromosomes were from S. phureja or S. tuberosum. Unique hybridizing fragments present in S. phureja but not in 'Pentland Crown' were identified. These S. phureja-specific restriction fragments were present in some of the dihaploid offspring of 'Pentland Crown'. Of the 5 clones that contained triploid cells 4 had S. phureja type banding. Four of the 10 aneusomatic clones that contained hyperploid cells had the unique S. phureja hybridizing fragments. We propose that ovules of 'Pentland Crown' were fertilized by pollen from S. phureja and that the aneusomatic clones were derived from triploid zygotes from which some of the S. phureja chromosomes were eliminated. We consider that this is an additional mechanism of dihaploid formation in potato. PMID- 24213333 TI - Association of protein amount polymorphism (PAP) among maize lines with performances of their hybrids. AB - It has been suggested that molecular foundations of phenotypic diversity reside in the variability of genome expression. This variability can be appraised through the polymorphism of individual protein amounts (PAP: protein amount polymorphism). Eight maize inbred lines and ten of their single-cross hybrids were analyzed by two-dimensional polyacrylamide gel electrophoresis in order to examine the potential of PAP for predicting hybrid vigor. The 28 possible pairs of lines were characterized for: (i) the number, H of expected heterozygous structural loci in their hybrid, in the sample of loci revealed by 2D-PAGE; (ii) four distance indices based on PAP; (iii) the hybrid values for five agromorphological characters measured in four different year/locations. For the subset of ten hybrids analyzed by 2D-PAGE, the number of cases of nonadditive inheritance (NA) was also counted. Whereas H appeared to be related neither to the PAP indices, nor to NA, nor to hybrid performances, PAP indices were correlated to NA, and both were positively associated to hybrid performances. The possibility that PAP is responsible for quantitative trait variation is discussed. This could result in the definition of biological predictors of heterosis. PMID- 24213334 TI - Genetic analysis of tolerance to low-phosphorus stress in maize using restriction fragment length polymorphisms. AB - An understanding of the genetic nature underlying tolerance to low-phosphorus (low-P) stress could aid in the efficient development of tolerant plant strains. The objective of this study was to identify the number of loci in a maize (Zea mays L.) population segregating for tolerance to low-P stress, their approximate location, and the magnitude of their effect.Seventy-seven restriction fragment length polymorphisms (RFLPs) were identified and scored in a maize F2 population derived from a cross between line NY821 and line H99. The F2 individuals were self-pollinated to produce F3 families. Ninety F3 families were grown in a sand alumina system, which simulated diffusion-limited, low-P soil conditions. The F3 families were evaluated for vegetative growth in a controlled-environment experiment. To identify quantitative trait loci (QTLs) underlying tolerance to low-P stress, the mean phenotypic performances of the F3 families were contrasted based on genotypic classification at each of 77 RFLP marker loci.Six RFLP marker loci were significantly associated with performance under low-P stress (P<0.01). One marker locus accounted for 25% of the total phenotypic variation. Additive gene action was predominant for all of the QTLs identified. Significant marker loci were located on four separate chromosomes representing five unlinked genomic regions. Two marker loci were associated with an additive by additive epistatic interaction. A multiple regression model including three marker loci and the significant epistatic interaction accounted for 46% of the total phenotypic variation. Heterozygosity per se was not predictive of phenotypic performance. PMID- 24213335 TI - Inheritance, linkage relationship and chromosomal localization of the glutamate oxaloacetate transaminase, acid phosphatase and diaphorase isozyme genes in Secale cereale L. AB - Genetic analysis of the inheritance of glutamate oxaloacetate transaminase (GOT), acid phosphatase (ACP) and diaphorase (DIA) in leaf tissue of rye revealed the involvement of four Got, four Acp and three Dia loci. Linkage analysis led to the arrangement of these and other previously described isozyme loci into four linkage groups located on chromosomes 3Rq, 4Rq, 6R, and 7Rq, respectively. Implications of these findings for possible translocation differences between chromosomes of S. cereale and S. montanum are discussed. A chi (2) component analysis which makes use of the entire potential of the information provided by codominantly inherited traits such as isozymes is described. PMID- 24213336 TI - Homoeology of rye chromosome arms to wheat. AB - Cytological markers such as diagnostic C-bands, telocentrics, and translocations were used to identify the arms of rye chromosomes associated with wheat chromosomes at metaphase I in ph1b mutant wheat * rye hybrids. Arm homoeologies of rye chromosomes to wheat were established from the results of metaphase I pairing combined with available data on the chromosomal location of homoeoloci series in wheat and rye. Only arms 1RS, 1RL, 2RL, 3RS, and 5RS showed normal homoeologous relationships to wheat. The remaining arms of rye appeared to be involved in chromosome rearrangements that occurred during the evolution of the genus Secale. We conclude that a pericentric inversion in chromosome 4R, a reciprocal translocation between 3RL and 6RL, and a multiple translocation involving 4RL, 5RL, 6RS, and 7RS are present in rye relative to wheat. PMID- 24213337 TI - Nucleolar organizer function in developing potato calli. AB - The number of transcriptionally active nucleolar organizer regions (NORs) of one monohaploid, one dihaploid and two tetraploids of Solanum tuberosum and one diploid S. phureja was established by the silver staining of metaphases in root meristems and in in vitro-cultured leaf explants. The maximum number of active NORs per cell was one per haploid set of chromosomes. One or more NORs could be inactive in cells of the tetraploid meristems and in non-polyploidized and polyploidized cells of the dihaploid and tetraploid explants. Inactivation was determined by genotype and tissue and could remain constant during in vitro culture. PMID- 24213338 TI - Phylogenetic relations in section Arachis based on seed protein profile. AB - Seed protein profiles of nine diploid species (2n = 20), ten tetraploid accessions, two synthetic amphidiploids and two autotetraploids (2n = 40) were studied using SDS-polyacrylamide gel electrophoresis. While the general profiles suggested considerable homology among these taxa in spite of speciation and ploidy differences, appreciable genetic differences were present to support the existing genomic divisions and sub-divisions in the section Arachis. A high degree of relationship was indicated between the two diploid species (A. duranensis containing the A genome and A. batizocoi (ICG 8210) containing the B genome) and tetraploids A. monticola/ A. hypogaea (2n = 40) containing AABB genome. Similar relationships were recorded between the AABB synthetic amphidiploid and the profile obtained from the mixture of protein of A. duranensis and A. batizocoi, suggesting that these two diploid species were the donors of the A and B genome, respectively, to tetraploid A. monticola/A. hypogaea. PMID- 24213339 TI - Gene action for cold tolerance in chickpea. AB - Six crosses were investigated using combining ability and generation mean analyses for reaction to cold tolerance in chickpea (Cicer arietinum L.). The combining ability variances revealed the significance of both additive and nonadditive gene effects, with preponderance of additive gene effects. The generation mean analysis revealed the presence of genie interactions in addition to additive and dominance gene effects. Among the interactions, additive*additive and dominance*dominance with duplicate epistasis were present. Cold tolerance was dominant over susceptibility to cold. Selection for cold tolerance would be more effective if dominance and epistatic effects were reduced after a few generations of selfing. PMID- 24213340 TI - Efficiency of potato breeding using FDR 2n gametes for multitrait selection and progeny testing. AB - The objective of this research was to compare the efficiency of the 4x*2x breeding scheme with the traditional 4x*4x method with respect to potato improvement. The basis for such a comparison was the parental value of four 2x and four 4x male parents from the International Potato Center (CIP) as measured by multitrait selection and progeny testing. The 2x parents produced 2n pollen by parallel spindles at anaphase II, which is genetically equivalent to a first division restitution (FDR) mechanism. Both 2x and 4x parents were crossed with four common 4x female parents. Thus, 32 families were evaluated over 2 years at four Peruvian locations. A selection index which considered tuber yield, tuber number, average tuber weight and specific gravity was used for multitrait selection. Three FDR 2x parents had better selection index scores than the 4x parents over the four locations. Estimates of broad-sense heritability for total yield using different number of replications and locations were calculated by using the variance components. The 4x * 2x breeding scheme was found to be better than the traditional 4x * 4x method since fewer replications and locations are required to evaluate tuber yield in 4x * 2x progenies than in 4x * 4x progenies. The FDR 2x parents were also better material than the 4x parents for testing combining ability for tuber yield of the 4x progenitors. This could be the result of the mode of FDR 2n pollen formation. The pollen of FDR 2x parents is more heterozygous, but more homogenous than n pollen from 4x parents. PMID- 24213341 TI - Highly asymmetric intergeneric nuclear hybrids between Nicotiana and Petunia: evidence for recombinogenic and translocation events in somatic hybrid plants after "gamma"-fusion. AB - Extremely asymmetric nuclear hybrids have been obtained via protoplast fusion in an intergeneric combination. Irradiated (cobalt(60),100 krad) kanamycinresistant Petunia hybrida mesophyll protoplasts were chemically fused with wild-type mesophyll protoplasts of Nicotiana plumbaginifolia. Eighty-six hybrid colonies were selected on kanamycin-containing medium, and twenty-four of these could be induced to regenerate numerous shoots. Cytological analysis of the regenerants showed the presence of a few chromosome fragments in some lines, and even a metacentric chromosome in yet another line. Besides additional chromosome fragments some lines only possessed typical Nicotiana chromosomes, and this at the diploid (2n = 2X = 20) as well as the tetraploid (2n = 2X = 40) level. Biochemical analysis showed that all regenerants had neomycin phosphotransferase activity (NPTII), which suggests that intergenomic recombination and or translocation events took place at least in those lines where no additional chromosome fragments could be detected. The presence of the NPTII gene was shown by Southern hybridization. All regenerants tested were fertile, and the segregation ratios for the kanamycin gene (for self and backcross pollinations to the recipient partner) for some of the regenerants correspond with Mendelian rules for a monogenic dominant marker. Most of the regenerants showed abnormal segregation ratios; in this case, no correlation could be made between segregation ratio and chromosome composition.Our results demonstrate the existence of intergenomic recombination and translocations evens in nuclear somatic hybrid plants obtained via "gamma"-fusion. PMID- 24213342 TI - Characterization of HSP-70 cognate proteins from wheat. AB - Animal and plant cells contain a family of constitutively expressed HSP-70 cognate proteins that are localized in different subcellular locations and are presumed to play a role in protein folding and transport. Utilizing antibodies raised against the yeast endoplasmicreticulum-localized HSP-70 cognate termed BiP/GRP-78, as well as antibodies raised against the Escherichia coli HSP-70 protein DnaK, we have identified and characterized a large family of closely related proteins in wheat. One protein band of 78 kDa that is apparently closely related to yeast BiP was localized in the endoplasmic reticulum. This band cross reacted with the yeast BiP but not with the DnaK-specific antibodies. The yeast BiP antibodies also recognized a cytoplasmic protein of 70 kDa that is probably related to the HSC-70 cognate proteins. These two proteins were further confirmed as HSP-70 cognates by their ability to bind to an ATP-agarose column. Probing of proteins from purified wheat mitochondrial preparations with the yeast BiP and DnaK-specific antibodies showed that this organelle contained a family of HSP-70 related proteins. The yeast BiP antibodies recognized two mitochondrial proteins of 60 and 58 kDa, but failed to detect any protein in the size rang of 70 to 80 kDa. However, the presence of immunologically distinct proteins of 90 and 78 kDa, as well as of lower molecular weight from this family in the mitochondria, was shown by probing with the DnaK-specific antibodies. A new protein of 30 kDa, cross-reacting with anti-yeast BiP antibodies, was detected only in developing seeds, close to their maturity. The evolution of HSP-70 cognate proteins in wheat as shown in this study is discussed. PMID- 24213343 TI - The occurrence and frequency of 2n pollen in 2x, 4x, and 6x wild, tuber-bearing Solanum species from Mexico, and Central and South America. AB - The occurrence of 2n pollen-producing plants was investigated in 187 plant introductions (PIs) of 38 wild species of tuber-bearing Solanum. These 2x, 4x, and 6x species are from Mexico, and Central and South America. The determination of 2n pollen-producing plants was conducted using acetocarmine glycerol. Plants with more than 1% large-size pollen were regarded as 2n pollen-producing plants. 2n pollen-producing plants were identified in the following species: 10 out of 12 Mexican 2x species, seven of nine South American 2x species, seven of seven Mexican and Central American 4x species, five of five South American 4x species, and five of five Mexican 6x species. The frequency of 2n pollen-producing plants varied among species at the same ploidy level, but the range of frequency, generally between 2 and 10% among species, was similar over different ploidy levels. The general occurrence of 2n pollen in both 2x and polyploid species, which are evolutionarily related, is evidence that the mode of polyploidization in tuber-bearing Solanums is sexual polyploidization. Furthermore, the frequencies of 2n pollen-producing plants in autogamous disomic polyploid species were not markably different from those of their related diploid species. It is thought that the frequent occurrence of 2n gametes with autogamy tends to disturb the fertility and consequently reduce fitness of polyploids. Thus, we propose that the breeding behavior of polyploids and the occurrence of 2n gametes may be genetically balanced in order to conserve high fitness in polyploid species in tuberbearing Solanum. PMID- 24213344 TI - Development and chromosomal localization of genome-specific markers by polymerase chain reaction in Brassica. AB - This paper reports the application of the RAPD (random amplification of polymorphic DNA sequence) markers in Brassica genetics. Forty-seven arbitrary decamer oligonucletides were used as primers to amplify genomic DNA by polymerase chain reaction. Some of the amplified products were genome specific and could be found in both diploid and derived amphidiploid species. Of a total of 65 such markers, 16 were A genome, 37 B genome, and 12 C genome specific. Of the 37 B genome-specific markers, 11 were mapped on four independent chromosomes of B. nigra with the aid of existing B. napus-nigra disomic alien addition lines. PMID- 24213345 TI - Agronomic evaluation of tissue-culture-derived soybean plants. AB - Genetic alterations of regenerated plants based on the tissue culture process (somaclonal variation) have become common for many plant species including soybean [Glycine max (L.) Merr.]. The objective of this study was to test for the presence of tissue-culture-derived genetic variation in eight agronomic traits in homozygous progeny regenerated by organogenesis using the commercially important cultivar Asgrow 'A3127.' A total of 86 lines derived by repeated self-pollination of nine regenerated plants was grown in two locations for 2 years. When compared to the unregenerated parent, statistically significant variation (P<0.05) was found for maturity, lodging, height, seed protein and oil, but not for seed quality, seed weight, or seed yield. All of the variation noted was beneficial and did not involve decreased yield. Since the differences were not large, the results indicate that the tissue culture process is not necessarily detrimental to plant performance, which is an important consideration since tissue culture techniques are used in many genetic engineering methods. PMID- 24213346 TI - A linkage map based on information from four F2 populations of maize (Zea mays L.). AB - Recently, maize (Zea mays L.) genetic maps based primarily upon segregating restriction fragment length polymorphisms (RFLPs) have been developed by several research groups. Some of the reported maps were based upon data from a single segregating population, whereas others were based upon information from several segregating populations. Potential problems with pooling information from several segregating populations have not been reported. These include the fact that few genetic markers are polymorphic in all populations, estimates of linkage may differ among populations, and population sizes may differ. We utilize the log likelihood statistic to genetically map partially overlapping sets of informative genetic markers, to test homogeneity of recombination among populations, and to present a composite RFLP linkage map based upon data pooled from four F2 populations. PMID- 24213347 TI - Formation of first division restitution (FDR) 2n-megaspores through pseudohomotypic division in ds-1 (desynapsis) mutants of diploid potato: routine production of tetraploid progeny from 2xFDR * 2xFDR crosses. AB - The level and mode of 2n megaspore formation was studied in full-sib diploid potato clones with either normal or desynaptic (ds-1ds-1) meiosis. Cytological analysis revealed that functional 2n megaspores produced by normal and desynaptic clones originate exclusively from 'second division restitution (SDR)' and 'first division restitution (FDR)', respectively. SDR 2n megaspores resulted from the omission of the second meiotic division following chromosome doubling after anaphase I, whereas FDR 2n megaspores resulted from a direct equational division of univalent chromosomes at anaphase I (pseudohomotypic division). Comparative data strongly indicated that the observed mechanisms of SDR and FDR 2n megaspore formation are extremes of a continuum that is being brought about by common genes for precocious chromosome division. Depending on the relative timing of cell cycle and chromosome division, this precocious chromosome division may impose postreductional (SDR) or prereductional (FDR) 'restitution' of the sporophytic chromosome number under normal synaptic and desynaptic conditions, respectively. The observed frequencies of 2n megaspores closely correlated with seed set, following pollination by tetraploid varieties and by desynaptic diploid clones with exclusive FDR 2n pollen formation. Up to 54.0 and 21.5 seeds/ fruit were obtained from normal synaptic (SDR) and desynaptic (FDR) progeny, respectively. The high frequency of segregants with either SDR or FDR 2n megaspore formation (78.0 and 45.2%, respectively) supports the hypothesis that sexual polyploidization is the driving force behind the origin and evolution of polyploid Solanum species. The present identification of diploid potato clones with consistent FDR 2n megaspore formation extends the opportunities for direct transfer of enhanced diploid germ plasm to tetraploids, and particularly advocates the feasibility of 2x(ds-1; FDR)*2x(ds-1; FDR) breeding schemes in cultivar development and the production of relatively vigorous and uniform true potato seed (TPS) varieties. Its potential value and limitations for breeding and the experimental induction of diplosporic apomixis are discussed. PMID- 24213348 TI - The use of IAA to overcome interspecific hybrid inviability in reciprocal crosses between Nicotiana tabacum L. and N. repanda Willd. AB - Flowering hybrid plants were obtained from reciprocal crosses between N. tabacum L. (2n=48) and N. repanda Willd. (2n = 48), in which cross incompatibility and hybrid inviability were manifested. Stylar pollination and ovule culture were used to overcome the cross incompatibility of stylar barriers and ovular death. It was shown that application of 2 mg/l indole-3-acetic acid (IAA) during the growth period, from the fiveto six-leaf stage to the flowering stage, is a useful and easy method to overcome hybrid inviability. PMID- 24213349 TI - Erratum. PMID- 24213350 TI - Distinct roles of a mitogen-activated protein kinase in cytokinesis between different life cycle forms of Trypanosoma brucei. AB - Mitogen-activated protein kinase (MAPK) modules are evolutionarily conserved signaling cascades that function in response to the environment and play crucial roles in intracellular signal transduction in eukaryotes. The involvement of a MAP kinase in regulating cytokinesis in yeast, animals, and plants has been reported, but the requirement for a MAP kinase for cytokinesis in the early branching protozoa is not documented. Here, we show that a MAP kinase homolog (TbMAPK6) from Trypanosoma brucei plays distinct roles in cytokinesis in two life cycle forms of T. brucei. TbMAPK6 is distributed throughout the cytosol in the procyclic form but is localized in both the cytosol and the nucleus in the bloodstream form. RNA interference (RNAi) of TbMAPK6 results in moderate growth inhibition in the procyclic form but severe growth defects and rapid cell death in the bloodstream form. Moreover, TbMAPK6 appears to be implicated in furrow ingression and cytokinesis completion in the procyclic form but is essential for cytokinesis initiation in the bloodstream form. Despite the distinct defects in cytokinesis in the two forms, RNAi of TbMAPK6 also caused defective basal body duplication/segregation in a small cell population in both life cycle forms. Altogether, our results demonstrate the involvement of the TbMAPK6-mediated pathway in regulating cytokinesis in trypanosomes and suggest distinct roles of TbMAPK6 in cytokinesis between different life cycle stages of T. brucei. PMID- 24213351 TI - High-resolution anion photoelectron spectra of TiO2-, ZrO2-, and HfO2- obtained by slow electron velocity-map imaging. AB - High-resolution anion photoelectron spectra of the Group 4 metal dioxides TiO2( ), ZrO2(-), and HfO2(-) are reported, using slow electron velocity-map imaging (SEVI) combined with ion trapping and cryogenic cooling. The resulting spectra exhibit sub-meV resolution with no congestion from hot bands. Electron affinities are obtained with greater precision than in previous photodetachment experiments, with values of 1.5892(5) eV, 1.6397(5) eV, and 2.1045(5) eV, for TiO2, ZrO2, and HfO2, respectively. We obtain precise values for all of the vibrational frequencies of the neutral X[combining tilde](1)A1 ground states, except for the nu3 mode of HfO2. Weak activity observed in the forbidden nu3 mode for TiO2 and ZrO2 is attributed to Herzberg-Teller coupling to the A(2)B2 excited state. PMID- 24213352 TI - Web Exclusives. The consult guys: perioperative risk assessment: can you get it right? PMID- 24213353 TI - Web Exclusives. The consult guys: a 23-year-old with a myocardial infarction: will you get the right diagnosis? PMID- 24213354 TI - Enkephalin knockdown in the basolateral amygdala reproduces vulnerable anxiety like responses to chronic unpredictable stress. AB - The endogenous enkephalins (ENKs) are potential candidates participating in the naturally occurring variations in coping styles and determining the individual capacities for adaptation during chronic stress exposure. Here we demonstrate that there is a large variance in individual behavioral, as well as in physiological outcomes, in a population of Sprague-Dawley rats subjected to 3 weeks of chronic unpredictable stress (CUS). Separation of resilient and vulnerable subpopulations reveals specific long-term neuroadaptation in the ENKergic brain circuits. ENK mRNA expression was greatly reduced in the posterior basolateral nucleus of amygdala (BLAp) in vulnerable individuals. In contrast, ENK mRNA levels were similar in resilient and control (unstressed) individuals. Another group of rats were used for lentiviral-mediated knockdown of ENK to assess whether a decrease of ENK expression in the BLAp reproduces the behavioral disturbances found in vulnerable individuals. ENK knockdown specifically located in the BLAp was sufficient to increase anxiety in the behavioral tests, such as social interaction and elevated plus maze when compared with control individuals. These results show that specific neuroadaptation mediated by the ENKergic neurotransmission in the BLAp is a key regulator of resilience, whereas a decrease of the ENK in the BLAp is a maladaptation mechanism, which mediates the behavioral dichotomy observed between vulnerable and resilient following 3 weeks of CUS. PMID- 24213357 TI - Facile synthesis of nano-sized hollow single crystal zeolites under mild conditions. AB - We report a method to synthesize hollow ZSM-5 single crystals of a size below 100 nm that could function as nanoreactors with access through the zeolite micropores only. In the first step, ZSM-5 is synthesized with the respective crystal size. In the second, the zeolite is base leached and acid washed under mild conditions. PMID- 24213355 TI - Impaired hippocampal neuroligin-2 function by chronic stress or synthetic peptide treatment is linked to social deficits and increased aggression. AB - Neuroligins (NLGNs) are cell adhesion molecules that are important for proper synaptic formation and functioning, and are critical regulators of the balance between neural excitation/inhibition (E/I). Mutations in NLGNs have been linked to psychiatric disorders in humans involving social dysfunction and are related to similar abnormalities in animal models. Chronic stress increases the likelihood for affective disorders and has been shown to induce changes in neural structure and function in different brain regions, with the hippocampus being highly vulnerable to stress. Previous studies have shown evidence of chronic stress-induced changes in the neural E/I balance in the hippocampus. Therefore, we hypothesized that chronic restraint stress would lead to reduced hippocampal NLGN-2 levels, in association with alterations in social behavior. We found that rats submitted to chronic restraint stress in adulthood display reduced sociability and increased aggression. This occurs along with a reduction of NLGN 2, but not NLGN-1 expression (as shown with western blot, immunohistochemistry, and electron microscopy analyses), throughout the hippocampus and detectable in different layers of the CA1, CA3, and DG subfields. Furthermore, using synthetic peptides that comprise sequences in either NLGN-1 (neurolide-1) or NLGN-2 (neurolide-2) involved in the interaction with their presynaptic partner neurexin (NRXN)-1, intra-hippocampal administration of neurolide-2 led also to reduced sociability and increased aggression. These results highlight hippocampal NLGN-2 as a key molecular substrate regulating social behaviors and underscore NLGNs as promising targets for the development of novel drugs for the treatment of dysfunctional social behaviors. PMID- 24213358 TI - Triptolide induces apoptosis in endometrial cancer via a p53-independent mitochondrial pathway. AB - Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and time-dependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z VAD-fmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered. PMID- 24213359 TI - Characteristics of growth and tropane alkaloid production in Hyoscyamus albus hairy roots transformed with Agrobacterium rhizogenes A4. AB - Hairy root culture of Hyoscyamus albus was established by transformation with Agrobacterium rhizogenes strain A4. The growth and production of five tropane alkaloids were investigated under various culture conditions. Among the four basal culture media tested, Woody Plant medium was the best for growth of the hairy roots, but a high amount of tropane alkaloids was obtained with Gamborg's B5 medium. Sucrose concentration in B5 medium had little effect on the growth, while 3% sucrose was suitable for the alkaloid production. Addition of KNO3 to Woody Plant medium affected the growth, whereas the alkaloid content was not markedly improved. Supplement of some metal ions to B5 medium stimulated the alkaloid production. In particular, Cu(2+) remarkably enhanced both the growth and the alkaloid yield. The hairy roots cultured under 16 h/day light survived for more than 32 days compared with those cultured in the dark. PMID- 24213360 TI - Transgenic turf-type tall fescue (Festuca amndinacea Schreb.) plants regenerated from protoplasts. AB - To improve turfgrasses using genetic engineering, we have developed a transformation system in turf-type tall fescue, one of the most important turfgrass species. Embryogenic cell cultures were established after callus induction from embryos of mature seed. The agarose-bead method with nurse cells was used to culture protoplasts and plants were regenerated from protoplasts of tall fescue cultured cells. To develop transgenic tall fescue plants, the hygromycin resistance gene and the beta-glucuronidase gene were introduced into the tall fescue protoplasts by electroporation. A high concentration (200 mg/l) of hygromycin was required to select transformed cells because of the high level of endogenous resistance to the antibiotic in tall fescue. Most of the transformed cells exhibited GUS activity and several plants were regenerated from these cells. The presence of introduced genes was confirmed by Southern blot hybridization of PCR amplified DNA from transgenic plants. PMID- 24213361 TI - Bioreactor studies on the effect of dissolved oxygen concentrations on growth and differentiation of carrot (Daucus carota L.) cell cultures. AB - A bioreactor control system was used to investigate the effects of two dissolved oxygen concentrations (10% and 100%) on the growth and differentiation of Daucus carota L. cell cultures. The strategy used allowed the dissolved oxygen concentration to be controlled without the need for changing either the agitator speed or the total gas flow rate. During the proliferation phase, reducing oxygen resulted in a lower growth rate and in a delay in sugar uptake kinetics. Nonetheless, varying levels of oxygen were observed to have no effect on the final dry biomass. The higher alcohol dehydrogenase activity obtained under reduced oxygen conditions suggests that proliferating cultures adapted to the hypoxic environment by inducing alcoholic fermentation. Cell differentiation was highly sensitive to reduced oxygen since under this condition, the somatic embryo production was inhibited by about 75%. Sugar uptake and embryo formation were also delayed. PMID- 24213362 TI - Somatic embryogenesis and plantlet regeneration from cell suspension cultures of Fagus sylvatica L. AB - Embryogenic cell suspension cultures and somatic embryos of five genotypes of beech, were obtained from aged cultures derived from immature zygotic embryos cultured on solid medium containing both 2, 4-dichlorophenoxyacetic acid and N6 benzyladenine. The origin of somatic embryos was traced from single cells. Embryos remained arrested at the globular stage on liquid media, further development was achieved after plating embryogenic aggregates on Murashige and Skoog's medium with half strength major salts supplemented with glutamine and low levels of growth regulators. Cultures of different genotypes showed significant differences in maturation frequency which was not affected by the hormone treatments assayed. The frequency of conversion of embryos into plantlets was low. This frequency increased after cold storage of embryos for up to 7 months. PMID- 24213363 TI - Plant regeneration from stem cortex expiant and protoplast cultures of Brassica juncea (mustard). AB - Plant regeneration from stem cortex explants of 13 genotypes of Brassica juncea was assessed. Regeneration was strongly affected by genotype, as up to 50.6 shoots were produced per 100 calli of the most responsive line (Blaze), whereas no shoots were obtained from less responsive lines (Zeml, Vniimk351). Blaze was chosen for B. juncea stem cortex protoplast isolation. After one week of culture, 11-14% of the cells had divided, and about 0.002% produced 1-2 mm colonies within 6 weeks. Up to 7% of these colonies gave rise to shoots upon transfer to plant regeneration medium. PMID- 24213364 TI - Plant regeneration from haploid cell suspension-derived protoplasts of Mediterranean rice (Oryza sativa L. cv. Miara). AB - More than 750 plants were regenerated from protoplasts isolated from microspore callus-derived cell suspensions of the Mediterranean japonica rice Miara, using a nurse-feeder technique and N6-based culture medium. The mean plating efficiency and the mean regeneration ability of the protocalluses were 0.5% and 49% respectively. Flow cytometric evaluation of the DNA contents of 7 month old-cell and protoplast suspensions showed that they were still haploid. Contrastingly, the DNA contents of leaf cell nuclei of the regenerated protoclones ranged from 1C to 5C including 60% 2C plants. This was consistent with the morphological type and the fertility of the mature plants. These results and the absence of chimeric plants suggest that polyploidization occurred during the early phase of protoplast culture. PMID- 24213365 TI - Isolation and molecular characterisation of a tuberisation-related cDNA clone from potato (Solanum tuberosum L.). AB - A cDNA clone of a gene which shows a large increase in transcript level in the stolon tip during the early stages of tuberisation in potato (Solanum tuberosum) has been isolated by differential screening. This gene is also expressed at low levels in other parts of the plant including leaves and stems. Sequence analysis and comparison did not reveal any significant similarity with other gene sequences in the EMBL database. DNA-blot analysis indicates that the gene is present as a single copy in the potato genome and a restriction fragment length polymorphism exists between wild type and cultivated potatoes. PMID- 24213366 TI - A plant selectable marker gene based on the detoxification of the herbicide dalapon. AB - A gene from Pseudomonas putida coding for a dehalogenase capable of degrading 2,2 dichloropropionic acid (2,2DCPA), the active ingredient of the herbicide dalapon, has been isolated and characterised. In plant transformation experiments the gene was shown to confer resistance to 2,2DCPA at a tissue culture level where 2,2DCPA could be used to select for transformants. At the whole plant level, transformed plants showed resistance to 2,2DCPA at concentrations up to 5 times the recommended dose rate of dalapon when it was sprayed on their leaves. At lower concentrations, the herbicide caused a non-lethal yellowing of sensitive plants which clearly distinguished them from resistant plants. The mode of action of chlorinated aliphatic acids is not known but they probably affect many enzyme pathways. The results described here are the first example of engineering a plant resistant to a herbicide that does not have one specific enzyme as its target site. This gene has several advantages as a marker in plant breeding and genetic studies. For example, the herbicide is readily available and has low toxicity, transformants can be selected at both the tissue culture and the whole plant level, a large number of transformed plants can easily be screened even in the field, and there is a very low probability of selecting spontaneous mutants. PMID- 24213367 TI - Protoplasts from cotyledon and hypocotyl of sunflower (Helianthus annuus L.): shoot regeneration and seed production. AB - Cotyledon and hypocotyl protoplasts of Helianthus annuus inbred line 47 302 bcd were embedded in alginate and plated on L4 medium (Lenee and Chupeau 1986). After one month, the calli were transferred on MSSH regeneration medium (Murashige and Skoog 1962; Schenk and Hildebrandt 1972) where they regenerated shoots (overall efficiency 10(-2)%). The shoots were elongated on B5 (Gamborg et al. 1968) medium first without hormones, then supplemented with GA3 and BAP (both 0.05 mg/l). In order to overcome the difficulty to induce rooting by classical methods, the elongated shoots were grafted on a sunflower rootstock. The grafted shoots produced flowers and seeds. Different factors have been shown to have an important influence on the capacity to regenerate shoots: the genotype, the physical culture conditions at the callus regeneration step (e.g. protoplasts embedded in alginate), and the media composition. PMID- 24213368 TI - Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures. AB - Cell suspension cultures developed from Artemisia annua exhibited antimalarial activity against Plasmodium faldparum in vitro both in the n-hexane extract of the plant cell culture medium and in the chloroform extract of the cells. Trace amounts of the antimalarial sesquiterpene lactone artemisinin may account for the activity of the n-hexane fraction but only the methoxylated flavonoids artemetin, chrysoplenetin, chrysosplenol-D and cirsilineol can account for the activity of the chloroform extract. These purified flavonoids were found to have IC50 values at 2.4 - 6.5 * 10(-5)M against P. falciparum in vitro compared with an IC50 value of about 3 * 10(-8)M for purified artimisinin. At concentrations of 5 * 10(-6)M these flavonoids were not active against P. falciparum but did have a marked and selective potentiating effect on the antiplasmodial activity of artemisinin. PMID- 24213370 TI - Protein kinase D1 has a key role in wound healing and skin carcinogenesis. AB - Protein kinase D (PKD) is a family of stress-responsive serine/threonine kinases implicated in the regulation of diverse cellular functions including cell growth, differentiation, apoptosis, and cell motility. Although all three isoforms are expressed in keratinocytes, their role in skin biology and pathology is poorly understood. We recently identified a critical role for PKD1 during reversal of keratinocyte differentiation in culture, suggesting a potential proproliferative role in epidermal adaptive responses. Here, we generated mice with targeted deletion of PKD1 in the epidermis to evaluate the significance of PKD1 in normal and hyperplastic conditions. These mice displayed a normal skin phenotype, indicating that PKD1 is dispensable for skin development and homeostasis. Upon wounding, however, PKD1-deficient mice exhibited delayed wound re epithelialization correlated with a reduced proliferation and migration of keratinocytes at the wound edge. In addition, the hyperplastic and inflammatory responses to topical phorbol ester were significantly suppressed, suggesting involvement of PKD1 in tumor promotion. Consistently, when subjected to the two stage chemical skin carcinogenesis protocol, PKD1-deficient mice were resistant to papilloma formation when compared with control littermates. These results revealed a critical proproliferative role for PKD1 in epidermal adaptive responses, suggesting a potential therapeutic target in skin wound and cancer treatment. PMID- 24213369 TI - Reduction in serine protease activity correlates with improved rosacea severity in a small, randomized pilot study of a topical serine protease inhibitor. PMID- 24213371 TI - Reversal of CD8 T-cell-mediated mucocutaneous graft-versus-host-like disease by the JAK inhibitor tofacitinib. AB - The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL 2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN gamma-inducible chemoattractants by keratinocytes, and IFN-gamma-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell-mediated mucocutaneous diseases in patients with GVHD. PMID- 24213372 TI - De novo anti-type VII collagen antibodies in patients with recessive dystrophic epidermolysis bullosa. PMID- 24213374 TI - Health-related quality of life in children with hemifacial microsomia: parent and child perspectives. AB - PURPOSE: To compare health-related quality of life (HRQOL) among children with and without hemifacial microsomia (HFM) as assessed by parents and the children themselves during the elementary school years. METHODS: One hundred thirty-six children with HFM (49 females, mean age = 6 years, 11.9 months, SD = 1.004) were compared with 568 matched controls (285 females, mean age = 6 years, 10.2 months, SD = 0.998) for parent and child responses on the PedsQL Version 4.0. RESULTS: After adjustment for sociodemographic factors, parent-reported summary scores were worse for affected children than control group children for physical (effect sizes [ES] = 0.26, p = .004), social (ES = 0.34, p = .001), and school (ES = 0.32, p = .001) functioning. There were no significant mean differences in summary scores based on children's self-reported functioning. CONCLUSIONS: Case control mean differences in HRQOL were more apparent based on parent report, but not child self-report. Summary score findings suggest that case parents have concerns about their child's HRQOL, particularly with respect to their child's physical, social, and school functioning. Additionally, our findings highlight the potential differences between child and parent perspectives and the importance of collecting data from multiple reporters. PMID- 24213373 TI - Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-mediated upregulation of death receptor 5 and downregulation of survivin. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted considerable attention owing to its selective killing of tumor cells but not normal cells. Melanoma shows weak response to TRAIL because of its low level of TRAIL death receptors. Here, we investigated whether indomethacin, a nonsteroidal anti-inflammatory drug, can potentiate TRAIL-induced apoptosis in melanoma cells. We showed that indomethacin was capable of promoting TRAIL-induced cell death and apoptosis in A375 melanoma cells. Mechanistically, indomethacin induced cell surface expression of death receptor 5 (DR5) in melanoma cells and also in various types of cancer cells. DR5 knockdown abolished the enhancing effect of indomethacin on TRAIL responses. Induction of the DR5 by indomethacin was found to be p53 independent but dependent on the induction of CCAAT/enhancer-binding protein homologous protein (CHOP). Knockdown of CHOP abolished indomethacin induced DR5 expression and the associated potentiation of TRAIL-mediated cell death. In addition, indomethacin-induced reactive oxygen species (ROS) production preceded upregulation of CHOP and DR5, and consequent sensitization of cells to TRAIL. We also found that indomethacin treatment downregulated survivin via ROS and the NF-kappaB-mediated signaling pathways. Interestingly, indomethacin also converted TRAIL-resistant melanoma MeWo and SK-MEL-5 cells into TRAIL-sensitive cells. Taken together, our results indicate that indomethacin can potentiate TRAIL-induced apoptosis through upregulation of death receptors and downregulation of survivin. PMID- 24213375 TI - Histone variants and sensing of chromatin functional states. AB - An extreme case of chromatin remodelling is the genome-wide exchange of histones with basic non-histone DNA-packaging proteins that occurs in post-meiotic male germ cells. The scale of this genome reorganization is such that chromatin needs to undergo a prior "preparation" for a facilitated action of the factors involved. Stage-specific incorporation of specialized histone variants, affecting large domains of chromatin, combined with histone post-translational modifications accompany the successive steps of the male genome reorganization. Recently, it has been shown that a testis-specific H2B variant, TH2B, one of the first identified core histone variants, replaces H2B at the time of cells' commitment into meiotic divisions and contributes to the process of global histone removal. These investigations also revealed a previously unknown histone dosage compensation mechanism that also ensures a functional interconnection between histone variant expression and histone post-translational modifications and will be further discussed here. PMID- 24213377 TI - Nuclear lamins: making contacts with promoters. AB - The nuclear lamina guards the genome and in many ways contributes to regulating nuclear function. Increasing evidence indicates that the lamina dynamically interacts with chromatin mainly through large repressive domains, and recent data suggest that at least some of the lamin-genome contacts may be developmentally significant. In an attempt to provide an additional meaning to lamin-genome contacts, a recent study characterized the association of gene promoters with A type lamins in progenitor and differentiated cells. Here, we discuss how A-type lamins interact with spatially defined promoter regions, and the relationship between these interactions, associated chromatin marks and gene expression outputs. We discuss the impact of A-type lamins on nucleus-wide and local chromatin organization. We also address how lamin-promoter interactions are redistributed during differentiation of adipocyte progenitors into adipocytes. Finally, we propose a model of lineage-specific "unlocking" of developmentally regulated loci and its significance in cellular differentiation. PMID- 24213376 TI - Tissue specificity in the nuclear envelope supports its functional complexity. AB - Nuclear envelope links to inherited disease gave the conundrum of how mutations in near-ubiquitous proteins can yield many distinct pathologies, each focused in different tissues. One conundrum-resolving hypothesis is that tissue-specific partner proteins mediate these pathologies. Such partner proteins may have now been identified with recent proteome studies determining nuclear envelope composition in different tissues. These studies revealed that the majority of the total nuclear envelope proteins are tissue restricted in their expression. Moreover, functions have been found for a number these tissue-restricted nuclear envelope proteins that fit with mechanisms proposed to explain how the nuclear envelope could mediate disease, including defects in mechanical stability, cell cycle regulation, signaling, genome organization, gene expression, nucleocytoplasmic transport, and differentiation. The wide range of functions to which these proteins contribute is consistent with not only their involvement in tissue-specific nuclear envelope disease pathologies, but also tissue evolution. PMID- 24213378 TI - Histone variant selectivity at the transcription start site: H2A.Z or H2A.Lap1. AB - Considerable attention has been given to the understanding of how nucleosomes are altered or removed from the transcription start site of RNA polymerase II genes to enable transcription to proceed. This has led to the view that for transcriptional activation to occur, the transcription start site (TSS) must become depleted of nucleosomes. However, we have shown that this is not the case with different unstable histone H2A variant-containing nucleosomes occupying the TSS under different physiological settings. For example, during mouse spermatogenesis we found that the mouse homolog of human H2A.Bbd, H2A.Lap1, is targeted to the TSS of active genes expressed during specific stages of spermatogenesis. On the other hand, we observed in trophoblast stem cells, a H2A.Z-containing nucleosome occupying the TSS of genes active in the G 1 phase of the cell cycle. Notably, this H2A.Z-containing nucleosome was different compared with other promoter specific H2A.Z nucleosomes by being heterotypic rather than being homotypic. In other words, it did not contain the expected two copies of H2A.Z per nucleosome but only one (i.e., H2A.Z/H2A rather than H2A.Z/H2A.Z). Given these observations, we wondered whether the histone variant composition of a nucleosome at an active TSS could in fact vary in the same cell type. To investigate this possibility, we performed H2A.Z ChIP-H2A reChIP assays in the mouse testis and compared this data with our testis H2A.Lap1 ChIP-seq data. Indeed, we find that different promoters involved in the expression of genes involved in distinct biological processes can contain either H2A.Z/H2A or H2A.Lap1. This argues that specific mechanisms exist, which can determine whether H2A.Z or H2A.Lap1 is targeted to the TSS of an active gene. PMID- 24213436 TI - Non-selectivity of ERG reductions in eyes treated for retinoblastoma. AB - PURPOSE: We have monitored retinal function in patients treated for retinoblastoma (primarily, but not exclusively by intra-arterial chemotherapy infusion) by electroretinography (ERG) recordings for the past 7 years. We here present data from 599 ERG studies of 108 patients, in which a complete ERG protocol including both photopic and scotopic recordings was performed, in justification of our frequent practice of reporting primarily 30-Hz photopic flicker amplitude data. METHODS: Patients referred for treatment of retinoblastoma underwent ERG recordings during examination under anesthesia whenever possible: at baseline and following most treatment sessions. Correlations were calculated for the complete datasets between the four primary amplitude response parameters: photopic single flash b-wave, photopic 30-Hz flicker peak-to-trough, scotopic rod-isolating b-wave, and scotopic maximal flash b-wave. RESULTS: Using our adaptation of the International Society for Clinical Electrophysiology of Vision-recommended standard ERG protocol, ERG responses of eyes of patients with untreated retinoblastoma or following traditional or intra arterial treatment for retinoblastoma show very high correlations between 30-Hz flicker amplitude responses and three other standard photopic and scotopic ERG response amplitudes. Reductions in ERG amplitudes seen in these eyes following treatment show no significant difference between retinal dysfunction estimated using rod- or cone-dominated responses. CONCLUSION: These observations support the use of photopic response amplitudes (especially in response to 30-Hz flicker) as the primary ERG outcome measure in studies of treated and untreated eyes with retinoblastoma when more complete ERG protocols may be impractical. PMID- 24213437 TI - Renal sympathetic denervation and ventricular arrhythmias: a case of electrical storm with multiple renal arteries. PMID- 24213438 TI - Chromosomal location and variability in wheat, barley and rye of a wheat gene encoding a bZIP protein (EmBP-1). PMID- 24213439 TI - Inheritance of isozyme and RFLP markers in Brassica campestris and comparison with B. oleracea. AB - Using primarily cDNA restriction fragment length polymorphism markers (RFLPs) previously located to Brassica oleracea (cabbage, 2n=18) chromosomes, we initiated a comparative RFLP map in an F2 population of B. campestris (turnip x mock pak-choi, 2n=20). As with B. oleracea, the genome of B. campestris showed extensive gene duplication, and the majority of detected duplicated loci were unlinked. Only 6 of the 49 identified loci were represented as a single copy, and 3 of these 6 were clustered on a single linkage group showing a distorted segregation ratio. Comparison with B. Oleracea indicates this synteny is conserved between species. Two other linkage groups also appeared syntenic between B. oleracea and B. campestris. One single copy locus appears to have changed synteny between B. oleracea and B. campestris. These observations suggest that B. oleracea and B. campestris share a common ancestor, but that chromosome repatterning has occurred during or after speciation. Within B. campestris, 5 loci appeared duplicated in one parent or the other, and 2 of these were linked. Differentiation through subspecies-specific duplication or deletion events is suggested as one mechansim for the evolution of numerous morphotypes within each of these species. PMID- 24213440 TI - Characterization of variability and relationships among components of partial resistance to leaf rust in CIMMYT bread wheats. AB - A study of spring bread wheat (Triticum aestivum) germ plasm developed at the International Maize and Wheat Improvement Center (CIMMYT) showed highly significant phenotypic variability for each component of partial resistance (namely, uredial appearance period, latency period, uredial number and uredial size) to Puccinia recondita f. sp. tritici. All of the wheat genotypes displayed longer uredial appearance and latency periods and decreased uredial number and uredial size when compared to the susceptible check cultivar 'Morocco'. Positive correlations between uredial appearance period and latency period, and uredial number and uredial size, and negative correlations between uredial appearance and latency periods and uredial number and uredial size, inclusive, suggested that the components of partial resistance were either tightly linked or under pleiotropic genetic control. Compared to 'Morocco', all entries had slow disease progress in the field and variation occurred in the germ plasm for the area under the leaf rust progress curve. Disease progress was negatively correlated with uredial appearance and latency periods, whereas a positive correlation was observed with uredial number and uredial size. Certain genotypes displayed high levels of partial resistance resulting in low disease incidence in the field. PMID- 24213441 TI - Homozygous-viable pericentric inversions for genetic control of Lucilia Cuprina. AB - The isolation of homozygous-viable pericentric inversions for inclusion in field female killing (FK) systems in Lucilia cuprina is described. From 7,236 irradiated chromosomes screened, 16 pericentric inversions were isolated. Four of these were viable as homozygotes. One of these, In (3LR) 14, possesses the properties required for inclusion in FK systems (tight linkage of one inversion break-point to the white-eye gene and substantial genetic exchange within the inversion in heterozygous females). PMID- 24213442 TI - The cost of herbicide resistance measured by a competition experiment. AB - The cost of resistance has been measured by a competition experiment over a range of densities, in the absence of herbicide treatment, on two nearly isogenic lines of Foxtail millet, differing in a chloroplastic resistance to herbicide. Three characters have been measured: shoot height, shoot weight, and seed production. Sensitive individuals were better competitors despite a larger decrease in production under within-biotype competition. The cost of resistance was density dependent and increased with density. The cost was higher when measured on seed production and reached 65% at the higher density for resistant individuals. This is compatible with the low frequency or the absence of that gene in natural populations. This work illustrates that the cost is easiest to observe when high levels of constraints are used. PMID- 24213443 TI - Bamboo germplasm screening with nuclear restriction fragment length polymorphisms. AB - Bamboo species are difficult to identify because flowering material is seldom available and taxonomy is of necessity based on vegetative characters. To evaluate the utility of restriction fragment length polymorphism (RFLP) analysis in bamboo systematics and germplasm screening, a library of random genomic probes from a Phyllostachys nigra PstI library was constructed. Probes from the library were used to screen bamboo germplasm consisting mostly of temperate bamboos of the genus Phyllostachys. RFLP variation was abundant, and species-specific patterns were readily obtained. Chloroplast DNA showed little variation among the bamboo accessions analyzed. PMID- 24213444 TI - Expression of unilateral incompatibility in pollen of Lycopersicon pennellii is determined by major loci on chromosomes 1, 6 and 10. AB - We have previously described gene introgression from the wild nightshade Solanum lycopersicoides into tomato (Lycopersicon esculentum) through the use of either diploid or sesquidiploid hybrids (the latter consisting of two genomes of L. esculentum and one genome of S. lycopersicoides). Both types of intergeneric hybrids display pollen sterility, but workable ovule fertility. Unilateral incompatibility prevents their direct hybridization with staminate L. esculentum. Pollen of a self-compattible form of the related wild species L. pennellii is compatible with pistils of L. esculentum x S. lycopersicoides hybrids. This trait was backcrossed from L. pennellii to L. esculentum in order to develop bridging lines that could be used to obtain progeny from the intergeneric hybrids and to study the inheritance of bridging ability. In progeny of L. esculentum x S. lycopersicoides hybrids pollinated with L. pennellii-derived bridging lines, preferential transmission of L. pennellii alleles was observed for certain isozyme and RFLP markers on chromosomes 1, 6 and 10. The skewed segregations suggest linkage to three major pollen-expressed compatibility loci. This was confirmed by observations of pollen tube growth, which indicated that compatibility with pistils of the diploid intergeneric hybrid occurred only in bridging lines at least heterozygous for the L. pennellii markers on chromosomes 1, 6 and 10. Compatibility with the sesquidiploid hybrid required only the chromosome 1 and 6 loci, indicating an apparent effect of gene dosage on expression of incompatibility in the pistil. In an F2 L. esculentum x L. pennellii population, preferential transmission of L. pennellii alleles was observed for the same markers on chromosomes 1 and 10, as well as other markers on chromosomes 3, 11, and 12, but not 6. The chromosome 1 pollen compatibility locus maps to or near the S-locus, which determines S-allele specificity. The results are discussed in relation to existing genetic models for unilateral incompatibility, including the possible involvement of the S-locus. PMID- 24213445 TI - Isolation and characterization of intergeneric somatic hybrids in the Apocynaceae family. AB - Protoplasts were isolated from callus cultures of Rauwolfia serpentina Benth., Rhazya stricta Decaisne, and Catharanthus roseus (L.) G. Don, or from leaves of Vinca minor L. Protoplast isolation, culture, and fusion techniques as well as hybrid screening systems were developed for these species, and hybrids were obtained. Hybrid combinations were Rauwolfia + Vinca, Rauwolfia + Catharanthus, Rauwolfia + Rhazya, and Catharanthus + Vinca. For hybrid isolation, the physiological complementation method was utilized. Analyses of the material obtained included a cytogenetic study of the chromosomes, a study of multiple molecular forms of transferases and esterases, and the blot hybridization of restricted nuclear DNA using ribosomal DNA as a probe. Hybrids were identified in all species' combinations tried. A ten-fold increase in the accumulation of raucaffricine (relative to the parental Rauwolfia strain) was observed in one cell line of the Rauwolfia + Vinca hybrid. Our studies indicated the genetic stability of the great majority of the hybrid cell lines over a period of more than 20 months of in vitro growth. No shoot morphogenesis has so far been observed in this material. PMID- 24213446 TI - PEG-mediated plastid transformation: a new system for transient gene expression assays in chloroplasts. AB - Evidence is presented for the introduction of functional copies of the GUS reporter gene with plastid regulatory signals into chloroplasts after treatment of Nicotiana plumbaginifolia leaf protoplasts with PEG. GUS-activity is found in cells derived from protoplasts treated with PEG in the presence of plasmids harbouring the GUS-gene under the control of plastid promoter and terminator signals (plastid-specific reporter gene constructions). The activity is maintained after chloroplast isolation and incubation with the protease thermolysin under conditions sufficient to completely remove the much higher transient nuclear/cytoplasmic expression of a GUS-gene carrying the CaMV 35S promoter. Likewise, GUS-activity derived from a plasmid coding for the nuclear/cytoplasmic expression of the reporter gene with a plastid transit presequence is also maintained after these procedures. These results indicate that PEG-treatment is a suitable protocol by which to introduce DNA into chloroplasts for the study of transient gene expression. PMID- 24213447 TI - Higher plant mitochondrial DNA expression : 2. Influence of nuclear background on the transcription of a mitochondrial open reading frame, ORF25. AB - Mitochondria are semi autonomous organelles, with their own genome and transcription/translation systems. Although the regulation of mitochondrial gene expression is fairly well characterized in the animal system, little is known about these processes in plants. We have been studying the expression of ORF25, a mitochondrial open reading frame, in normal male-fertile maize. In all the N lines that we have examined, the ORF25 transcript pattern is similar, except for that in B37N. We have compared ORF25 transcription patterns between B73N and B37N: B73N has one major transcript of 2,300 nucleotides and two minor transcripts of 3,400 and 1,600 nucleotides, while B37N has a single transcript, 3,400 bases long. The ORF25 reading frame and 5' flanking regions have been analyzed by restriction mapping and found to be identical in these lines. Interestingly, the F1 progeny from reciprocal crosses between B73N and B37N have ORF25 transcript patterns identical to B73N. This suggests that the process of mitochondrial transcription is influenced by nuclear factors in normal cytoplasm. This factor(s) appears to be dominant in B73N and the F1 progeny. S1 nuclease analyses have revealed that identical fragments are protected in B73N and the F1 hybrids, indicating that the ORF25 transcripts in the F1 progeny are identical on the 5' ends to those of the parent B73N. This nuclear regulation may be at the level of initiation of transcription or processing of the mtRNA. PMID- 24213448 TI - The presence of the enhanced K/Na discrimination trait in diploid Triticum species. AB - A number of accessions of the three species of diploid wheat, Triticum boeoticum, T. monococcum, and T. urartu, were grown in 50 mol m(-3) NaCl+2.5 mol m(-3) CaCl2. Sodium accumulation in the leaves was low and potassium concentrations remained high. This was not the case in T. durum grown under the same conditions, and indicates the presence in diploid wheats of the enhanced K/Na discrimination character which has previously been found in Aegilops squarrosa and hexaploid wheat. None of the accessions of diploid wheat showed poor K/Na discrimination, which suggests that if the A genome of modern tetraploid wheats was derived from a diploid Triticum species, then the enhanced K/Na discrimination character became altered after the formation of the original allopolyploid. Another possibility is that a diploid wheat that did not have the enhanced K/Na discrimination character was involved in the hybridization event which produced tetraploid wheat, and that this diploid is now extinct or has not yet been discovered. PMID- 24213449 TI - Differences between, and possible origins of, the cytoplasms found in fertile and male-sterile onions (Allium cepa L.). AB - The DNA of the organellar genomes of Allium cepa has been examined to detect restriction fragment length polymorphisms. Differences can be shown between both the chloroplastal and mitochondrial genomes of the N and cms-S cytoplasms in their restriction fragment profiles. Southern blot analysis of the mtDNA profiles using probes containing defined mitochondrial genes also detected polymorphisms. No differences can be shown between the organellar genomes of the N and cms-T onions by either of these techniques. These data indicate different origins for the two sterility-conferring cytoplasms, suggesting autoplasmic and alloplasmic origins for the cms-T and cms-S cytoplasms, respectively. No evidence of the presence of virus-like particles was found in any of the cytoplasms. PMID- 24213450 TI - Structural studies of microsporogenesis in fertile and male-sterile onions (Allium cepa L.) containing the cms-S cytoplasm. AB - The structure of anther tissues has been studied during microsporogenesis in male sterile and -fertile onions. Three types of abnormal tapetal behaviour have been observed within the single line II/3ms containing the cms-S cytoplasm: type 1, the premature breakdown of the tapetum at the tetrad stage, type 2, the hypertrophy of the tapetum after the diad stage followed by its premature autolysis and, type 3, in which the tapetum remains in good condition but for an abnormally long period of time. Tapetal autolysis proceeds in the same manner in both male-steriles and -fertiles with only the stage at which it occurs differing between the types of plants. Mitochondria were prominent in the tapetal tissue of all onion types throughout all stages of microsporogenesis and were still visible during the last stages of tapetal autolysis. In a detailed study of type 2 behaviour, no differences in mitochondrial volumes were found until the tapetum hypertrophied. PMID- 24213451 TI - Maternal, paternal, additive, and dominance components of variance in Gerbera. AB - Estimates of additive, dominance, maternal, and paternal components of variance were obtained for a sample of 18 traits, including measurements of yield, scapes, flowers, disk, ray and trans florets, leaves, and branching in the Davis population of Gerbera hybrida. The results, based on the covariance of reciprocals, indicate that although heritability averaged 0.52, extranuclear maternal or paternal effects are not important sources of variability. Therefore, reciprocal differences do not seriously affect estimates of additive variance or heritability in this population. PMID- 24213452 TI - Genetic analysis of rye (Secale cereale L.) Genetics of male sterility of the G type. AB - The genetics and relationships between the genes in rye located in the nucleus and cytoplasm of the male sterility of the G-type were investigated. A factor inducing male sterility was found in the cytoplasms or rye cv Schlagler alt and rye cv Norddeutscher Champagner. Monogenic inheritance was observed in linkage tests. Using primary trisomies of rye cv Esto, the nuclear gene ms1 was found to be located on chromosome 4R. Modifying genes, probably masked in normal cytoplasm but expressed in male-sterility-inducing cytoplasm together with gene ms1, were located on chromosomes 3R (ms2) and 6R (ms3). Mono-, di-, and trigenic inheritance types were found in backcross progenies of trisomies. PMID- 24213453 TI - Higher plant mitochondrial DNA expression : 1. Variant expression of the plant mitochondrial open reading frame, ORF25, in B37N and B73N maize lines. AB - In studying the process of mitochondrial transcription, mutants that show altered gene expression as evidenced from transcript pattern differences are a valuable resource. However, such mutants are difficult to find since changes in mitochondrial gene expression will most likely be lethal. Several laboratories have been investigating cytoplasmic male-sterile mutants in maize and have reported changes in transcription patterns due to nuclear background influences on the complex chimeric gene region TURF-2H3 in T-cms. There have been no reports of altered transcription patterns for N cytoplasm that can be attributed to nuclear background differences. Through a Northern hybridization analysis of ORF25 transcription in a number of N lines, we reported invariant expression of this region. Subsequently, we have discovered a line B37N, which shows the presence of a single ORF25-specific transcript of 3,400 nucleotides, in contrast to the transcript sizes of 3,400, 2,300 and 1,600 displayed by most of the cytoplasms we have examined. Experiments presented in this communication demonstrate that the differences in the B37N, ORF25 transcript pattern map to the 5' flanking sequences of the reading frame. Using restriction enzyme mapping and Southern hybridization analysis, no detectable differences were found in the transcription unit structure for this reading frame in B37N and B73N, which shows the standard, three-transcript pattern. Analysis of nuclear background influences indicates that the transcript patterns for this open reading frame are dependent on nuclear background. These data are presented in part 2 of this study. PMID- 24213454 TI - alpha-Amylase structural genes in rye. AB - Rye alpha-Amy1, alpha-Amy2, and alpha-Amy3 genes were studied in the cross between inbred lines using wheat alpha-amylase cDNA probes. The alpha-Amy1 and alpha-Amy2 probes uncovered considerable restriction fragment length polymorphism, whereas the alpha-Amy3 region was much more conserved. The numbers of restriction fragments found and the F2 segregation data suggest that there are three alpha-Amy1 genes, two or three alpha-Amy2 genes, and three alpha-Amy3 genes in rye. These conclusions were supported by a simultaneous study of alpha-amylase isozyme polymorphism. The F2 data showed the three individual alpha-Amy1 genes to span a distance of 3cM at the locus on chromosome 6RL. The genes were mapped relative to other RFLP markers on 6RL. On chromosome 7RL two alpha-Amy2 genes were shown to be separated by 5 cM. Linkage data within alpha-Amy3 on 5RL were not obtained since RFLP could be detected at only one of the genes. PMID- 24213455 TI - Introduction of D-genome chromosomes from Aegilops squarrosa L. into tetraploid triticale (AB)(AB)RR (2n=28). AB - Tetraploid triticale with the genome constitution (ABD) (ABD)RR (2n=4x=28) selected from the progenies of DDRR x (AB)(AB)RR hybrids (D(AB)RR) were karyotyped using C-banding. The aneuploidy frequency was 10.7% with 4.4% hypoploids and 6.3% hyperploids in the F5. Among 67 plants having 28 chromosomes, 41.8% had a stabilized karyotype, while 58.2% were unstabilized with at least one homoeologous group segregating for A-, B- or D-genome chromosomes. The stabilized plants represented ten different karyotypes that contained one to five disome substitutions of D-genome chromosomes for A- or B-genome chromosomes. Two (BD) (BD)RR tetraploids had no A-genome chromosomes. The average number of D substitutions was 3.0 per line. Of the seven substitutions possible only one, 4D(4B), was not present. In the progeny of plants selected for fertility a selection pressure acted against wheat chromosomes 1B, 3B, 4D and 7D. The most favoured chromosome constitution of the (ABD) mixed genome was 1D, 2A, 3D, 4B, 5B, 6A and 7B. Plants of that karyotype but with a heterologous pair of chromosomes 5B and 5D had the best seed set. Evolutionary and breeding aspects of tetraploid triticale are discussed. PMID- 24213456 TI - Generation means analysis for productivity in two diverse peanut crosses. AB - Utilization of exotic germplasm resources for population improvement in peanut (Arachis hypogaea L.) has increased as the need to increase genetic diversity among peanut cultivars was recognized. Progeny of crosses of two unadapted germplasm lines (GP-NC 343 and FESR-11-P11-32) with an adapted cultivar ('NCV11') of peanut were evaluated for the genetic factors influencing the inheritance of yield and fruit characters in crosses among diverse lines. Objectives were to (1) estimate the relative importance of additive and nonadditive genetic effects in the inheritance of yield and fruit characters in two diverse peanut crosses; (2) determine the proportion of exotic germplasm that gave the optimum combination of mean productivity and genetic variability for each of the crosses; (3) relate the results to theories regarding the transfer of desirable alleles from exotic germplasm into adapted breeding populations. Crosses and backcrosses were made to generate germplasm lines (ten generations) ranging from 0 to 100% exotic germplasm for each cross. The populations were evaluated in replicated field trials. Yield and six fruit characters were measured, and a weighted analysis of variance was conducted to determine if significant differences existed among generations. Generation means analyses were performed for each trait measured in each of the crosses using both three- and six-parameter models, which were tested for goodness-of-fit with a joint-scaling test. Significant differences were detected among generations for most traits measured in both crosses. Estimates of additive genetic effects were significant for pod weight and seed weight in cross 1 ('NC-V11' x GP-NC 343) and for all traits in cross 2 ('NC-V11' x FESR-11-P11 32) except seed?pod ratio. Significant estimates of dominance effects were found for pod length, pod width, and pod weight in cross 1 and for pod length in cross 2. No significant estimates of digenic effects were observed in cross 1, whereas in cross 2 estimates of additive x dominance epistatic effects were significant for yield and pod length, while estimates of additive x additive effects were significant for seed number. Regression of trait means on generations showed a curvilinear response for all traits in cross 1 except seed weight, which gave a linear response. For all traits in cross 2, the relationship between productivity and proportion of unadapted germplasm was effectively linear. Based on generation means and variances, progeny from the first or second backcross generation to the recurrent parent should be expected to give an optimum combination of mean productivity and relative variability in the population. PMID- 24213457 TI - Distribution and evolution of two satellite DNAs in the genus Beta. AB - EcoRI monomers of a highly repetitive DNA family of Beta vulgaris have been cloned. Sequence analysis revealed that the repeat length varies between 157-160 bp. The percentage of AT-residues is 62% on average. The basic repeat does not show significant homology to the BamHI sequence family of B. vulgaris that was analyzed by us earlier. Both the EcoRI and BamHI sequences are investigated and compared to each other with respect to their genomic organization in the genus Beta. Both repeats were found to be tandemly arranged in the genome of B. vulgaris in a satellite-like manner. The EcoRI satellite DNA is present in three sections (Beta, Corollinae and Nanae) of the genus, whereas the BamHI satellite DNA exists only in the section Beta. The distribution of the EcoRI and BamHI satellite families in the genus is discussed with respect to their evolution. PMID- 24213459 TI - Improved uniformity in high-performance organic photovoltaics enabled by (3 aminopropyl)triethoxysilane cathode functionalization. AB - Organic photovoltaics have the potential to serve as lightweight, low-cost, mechanically flexible solar cells. However, losses in efficiency as laboratory cells are scaled up to the module level have to date impeded large scale deployment. Here, we report that a 3-aminopropyltriethoxysilane (APTES) cathode interfacial treatment significantly enhances performance reproducibility in inverted high-efficiency PTB7:PC71BM organic photovoltaic cells, as demonstrated by the fabrication of 100 APTES-treated devices versus 100 untreated controls. The APTES-treated devices achieve a power conversion efficiency of 8.08 +/- 0.12% with histogram skewness of -0.291, whereas the untreated controls achieve 7.80 +/ 0.26% with histogram skewness of -1.86. By substantially suppressing the interfacial origins of underperforming cells, the APTES treatment offers a pathway for fabricating large-area modules with high spatial performance uniformity. PMID- 24213458 TI - Atomoxetine-induced mydriasis in a child patient. PMID- 24213460 TI - Association of Differentiation-Related Gene-1 (DRG1) with Breast Cancer Survival and in Vitro Impact of DRG1 Suppression. AB - Differentiation-related gene-1, DRG1, is a metastasis suppressor gene whose expression has been shown to be dysregulated in a number of malignancies. The current study examines the expression of DRG1 in a clinical breast cohort and its association with a number of clinical pathological factors using quantitative polymerase chain reaction. Additionally, DRG1 expression is targeted in vitro using ribozyme transgene technology to explore the function of DRG1 in two human breast cancer cell lines. Low levels of DRG1 were found in patients who developed metastasis (p = 0.036) and who died of breast cancer (p = 0.0048) compared to disease free patients. Knockdown of DRG1 also resulted in significantly increased invasion and motility, but decreased matrix-adhesion in MCF7 cells. Knockdown of DRG1 seemed to have minimal impact on the cellular functions of the MDA-MB-231 breast cancer cell line causing no significant differences in cell growth, invasion, motility or matrix-adhesion. Thus, DRG1 appears to be linked to development of metastasis and death in patients who died as a result of breast cancer and may be useful as a prognostic factor as its knockdown appears to be linked with increased invasion and motility and decreased adhesion in MCF7 breast cancer cells. PMID- 24213461 TI - Preclinical cancer chemoprevention studies using animal model of inflammation associated colorectal carcinogenesis. AB - Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described. PMID- 24213463 TI - Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics. AB - There is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitative methods which reliably measure biomarker expression. Our study assesses reliability of automated immunohistochemistry (IHC) scoring compared to manual scoring of five selected biomarkers in a tissue microarray (TMA) of 63 human breast cancer cases, and correlates these markers with clinico-pathological data. TMA slides were scanned into an Ariol Imaging System, and histologic (H) scores (% positive tumor area x staining intensity 0-3) were calculated using trained algorithms. H scores for all five biomarkers concurred with pathologists' scores, based on Pearson correlation coefficients (0.80-0.90) for continuous data and Kappa statistics (0.55-0.92) for positive vs. negative stain. Using continuous data, significant association of pERK expression with absence of LVI (p = 0.005) and lymph node negativity (p = 0.002) was observed. p53 over-expression, characteristic of dysfunctional p53 in cancer, and Ki67 were associated with high grade (p = 0.032 and 0.0007, respectively). Cyclin D1 correlated inversely with ER/PR/HER2-ve (triple negative) tumors (p = 0.0002). Thus automated quantitation of immunostaining concurs with pathologists' scoring, and provides meaningful associations with clinico-pathological data. PMID- 24213462 TI - Ovarian cancer stroma: pathophysiology and the roles in cancer development. AB - Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers. PMID- 24213464 TI - Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-alpha. AB - Membrane type-1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of proMMP-2. In this study we examined MT1-MMP expression in primary acute myeloid leukemia (AML) cells. Because tumor necrosis factor (TNF)-alpha is known to be elevated in AML, we also investigated the effect of TNF-alpha on MT1-MMP expression. We found (i) MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii) activation of proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii) inhibition of proMMP-2 activation and trans-Matrigel migration of AML cells by gene silencing using MT1 MMP siRNA. Moreover, recombinant human TNF-alpha upregulated MT1-MMP expression in AML cells resulting in enhanced proMMP-2 activation and trans-Matrigel migration. Thus, AML cells express MT1-MMP and TNF-alpha enhances it leading to increased MMP-2 activation and most likely contributing to the invasive phenotype. We suggest that MT1-MMP, together with TNF-alpha, should be investigated as potential therapeutic targets in AML. PMID- 24213465 TI - Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis. AB - Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25 hydroxyvitamin D-1a-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24 hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression. PMID- 24213466 TI - Neuroendocrine tumors of the lung. AB - Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1-G3) and the extent of differentiation (well differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung. PMID- 24213467 TI - Endometrial serous carcinoma: its molecular characteristics and histology specific treatment strategies. AB - Endometrial cancer is the fourth most common malignancy in women, with most cases being classified as early stage endometrioid tumors that carry a favorable prognosis. The endometrial serous histological subtype (ESC), however, while only accounting for 10% of all endometrial cancers is responsible for a disproportionate number of deaths. Unlike the estrogen-dependent, well differentiated endometrioid tumors, which are commonly associated with a younger age of onset, ESCs are estrogen-independent and tend to present at an advanced stage and in older women. Treatment for ESC entails aggressive surgery and multimodal adjuvant therapy. In this review, we describe the clinical behavior, molecular aspects, and treatment strategies for ESC. PMID- 24213468 TI - Succinate dehydrogenase B subunit immunohistochemical expression predicts aggressiveness in well differentiated neuroendocrine tumors of the ileum. AB - Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index <=2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene. PMID- 24213469 TI - Characterization of the Tumor-Microenvironment in Patient-Derived Cervix Xenografts (OCICx). AB - RATIONALE: The tumor microenvironment (TME) is heterogeneous including both malignant and host cell components as well as regions of hypoxia, elevated interstitial fluid pressure (IFP) and poor nutrient supply. The quantitative extent to which the microenvironmental properties of primary tumors are recapitulated in xenograft models is not well characterized. METHODS: Xenografts were generated by implanting tumor biopsies directly into the cervix of mice to create a panel of orthotopically-passaged xenografts (OCICx). Tumors were grown to ~1 cm (diameter) and IFP measurements recorded prior to sacrifice. Enlarged para-aortic lymph nodes (>1-2 mm) were excised for histologic confirmation of metastatic disease. Quantitative histological analysis was used to evaluate hypoxia, proliferation, lymphatic and blood vessels in the epithelial and stromal regions of the xenografts and original patient tumour. RESULTS: IFP and nodal disease were not correlated with tumor engraftment. IFP measurements in the xenografts were generally lower than those in the patient's tumor. Lymphatic metastasis increased with passage number as did levels of hypoxia in the epithelial component of the xenografts. The blood vessel density in the stromal component of the xenografts increased in parallel. When all the markers were compared between the biopsy and the respective 3rd generation xenograft 10 of 11 tumors showed a good correlation. CONCLUSIONS: This ongoing study provides characterization about tumoral and stromal heterogeneity in a unique orthotopic xenograft model. PMID- 24213470 TI - A microRNA Link to Glioblastoma Heterogeneity. AB - Glioblastomas (GBM) are one of the most malignant adult primary brain tumors. Through decades of research using various model systems and GBM patients, we have gained considerable insights into the mechanisms regulating GBM pathogenesis, but have mostly failed to significantly improve clinical outcome. For the most part GBM heterogeneity is responsible for this lack of progress. Here, we have discussed sources of cellular and microenvironmental heterogeneity in GBMs and their potential regulation through microRNA mediated mechanisms. We have focused on the role of individual microRNAs (miRNA) through their specific targets and miRNA mediated RNA-RNA interaction networks with the potential to influence various aspects of GBM heterogeneity including tumor neo-vascularization. We believe a better understanding of such mechanisms for regulation of GBM pathogenesis will be instrumental for future therapeutic options. PMID- 24213471 TI - Therapeutic targeting of hyaluronan in the tumor stroma. AB - The tumor stroma, consisting of non-malignant cells and the extracellular matrix, undergoes significant quantitative and qualitative changes throughout malignant transformation and tumor progression. With increasing recognition of the role of the tumor microenvironment in disease progression, stromal components of the tumor have become attractive targets for therapeutic intervention. Stromal accumulation of the glycosaminoglycan hyaluronan occurs in many tumor types and is frequently associated with a negative disease prognosis. Hyaluronan interacts with other extracellular molecules as well as cellular receptors to form a complex interaction network influencing physicochemical properties, signal transduction, and biological behavior of cancer cells. In preclinical animal models, enzymatic removal of hyaluronan is associated with remodeling of the tumor stroma, reduction of tumor interstitial fluid pressure, expansion of tumor blood vessels and facilitated delivery of chemotherapy. This leads to inhibition of tumor growth and increased survival. Current evidence shows that abnormal accumulation of hyaluronan may be an important stromal target for cancer therapy. In this review we highlight the role of hyaluronan and hyaluronan-mediated interactions in cancer, and discuss historical and recent data on hyaluronidase based therapies and the effect of hyaluronan removal on tumor growth. PMID- 24213473 TI - Updates in antiplatelet agents used in cardiovascular diseases. AB - BACKGROUND: Antiplatelet therapy is a cornerstone in coronary artery disease management. However, patients with acute coronary syndrome still remain at risk of recurrent cardiovascular events despite the advance of medical therapy. OBJECTIVE: This article provides a review of antiplatelet agents used in cardiovascular diseases and focus on updates in the past 5 years. METHOD: Peer reviewed clinical trials and relevant treatment guidelines were identified from MEDLINE and Current Content database (from 1966 to April 15, 2013) using search terms aspirin, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa inhibitors, antiplatelet agents, coronary artery disease, acute coronary syndrome, pharmacology, pharmacokinetics, and pharmacodynamics. Citations from the available articles were also reviewed for additional references. RESULTS: In unstable angina and non-ST-segment elevation myocardial infarction (MI), dual antiplatelet therapy (aspirin and clopidogrel) demonstrated a reduction in death from cardiovascular causes, nonfatal MI, or stroke (relative risk 0.80; 95% confidence interval [CI], 0.72-0.90). In ST-segment elevation MI, dual antiplatelet therapy reduced the rate of occluded infarct-related artery/death or recurrent MI (95% CI, 24%-47%). Newer agents such as prasugrel, when compared to clopidogrel, reduced death from vascular causes, MI, or stroke in patients undergoing percutaneous coronary intervention (PCI; hazard ratio [HR], 0.81; 95% CI 0.73-0.90) but not in those receiving medical management only. When compared to clopidogrel, ticagrelor reduces death from vascular causes, MI, or stroke (HR: 0.84; 95% CI, 0.77-0.92) in patients undergoing PCI or receiving medical management only. Both the agents, however, increase the risk of bleeding in certain patient population. CONCLUSIONS: In the last 5 years, newer antiplatelet agents, including prasugrel and ticagrelor, have been demonstrated to reduce recurrent cardiovascular events compared to standard therapy and, however, also caused increase bleeding in selected patient populations. Newer agents including shorter acting P2Y12 inhibitor or antiplatelets that target other receptors are being evaluated to improve/maintain therapeutic efficacy yet minimize the risk of bleeding. PMID- 24213475 TI - Epigenetics: WIP1 creates hush and havoc. PMID- 24213476 TI - Three-dimensional stereoscopic imaging modality based on a single optical channel and detector. AB - A three-dimensional stereoscopic imaging modality (3D-SIM) based on a single optical channel and detector was developed to overcome some of the limitations of conventional 3D-SIM. It produces 3-D stereoscopic images by adjusting the angle of a transparent rotating deflector (TRD) to generate disparity between left and right images. The angular effect of the TRD was demonstrated to investigate the feasibility of the proposed method in 3-D stereoscopic image generation. Results indicate that image disparity increased as a function of the rotation angles of the TRD, while maintaining adequate 3-D perception. These results are expected to facilitate the practical use of a 3D-SIM in medicine. PMID- 24213474 TI - Life history trade-offs in cancer evolution. AB - Somatic evolution during cancer progression and therapy results in tumour cells that show a wide range of phenotypes, which include rapid proliferation and quiescence. Evolutionary life history theory may help us to understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly, whereas those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity, which has potential implications for understanding 'cancer stem cells'. Life history theory suggests that different therapy dosing schedules might select for fast or slow life history cell phenotypes, with important clinical consequences. PMID- 24213472 TI - Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis. AB - Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don't alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL) protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis. PMID- 24213477 TI - Study of dynamic pressure-induced refractive index change using derivative total reflection method. AB - We report the dynamic refractive index (RI) change of tissue under a stepped compression load using a custom-built pressure apparatus. Angle-dependent reflectance profiles of biotissue samples are recorded, and the RI values are resolved using the derivative total reflection method. These results are relevant for understanding the mechanism of mechanical optical clearing, for investigating tissue dynamics under mechanical stimuli, and for other biomedical applications. PMID- 24213478 TI - Optical detection of carotenoid antioxidants in human bone and surrounding tissue. AB - Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status. PMID- 24213479 TI - Improved alpha-amylase production by Aspergillus oryzae after a double deletion of genes involved in carbon catabolite repression. AB - In filamentous fungi, the expression of secretory glycoside hydrolase encoding genes, such as those for amylases, cellulases, and xylanases, is generally repressed in the presence of glucose. CreA and CreB have been observed to be regulating factors for carbon catabolite repression. In this study, we generated single and double deletion creA and/or creB mutants in Aspergillus oryzae. The alpha-amylase activities of each strain were compared under various culture conditions. For the wild-type strain, mRNA levels of alpha-amylase were markedly decreased in the later stage of submerged culture under inducing conditions, whereas this reduced expression was not observed for single creA and double creA/creB deletion mutants. In addition, alpha-amylase activity of the wild-type strain was reduced in submerged culture containing high concentrations of inducing sugars, whereas all constructed mutants showed higher alpha-amylase activities. In particular, the alpha-amylase activity of the double deletion mutant in a medium containing 5% starch was >10-fold higher than that of the wild type strain under the same culture conditions. In solid-state cultures using wheat bran as a substrate, the alpha-amylase activities of single creA and double deletion mutants were >2-fold higher than that of the wild-type strain. These results suggested that deleting both creA and creB resulted in dramatic improvements in the production of secretory glycoside hydrolases in filamentous fungi. PMID- 24213481 TI - Effects of empathy and conflict resolution strategies on psychophysiological arousal and satisfaction in romantic relationships. AB - The present research builds upon the extant literature as it assesses psychophysiological factors in relation to empathy, conflict resolution, and romantic relationship satisfaction. In this study, we examined physiological reactivity of individuals in the context of emotionally laden interactions with their romantic partners. Participants (N = 31) completed self-report measures and attended in-person data collection sessions with their romantic partners. Participants were guided through discussions of problems and strengths of their relationships in vivo with their partners while we measured participants' skin conductance level (SCL) and interbeat interval (IBI) of the heart. We hypothesized that participants' level of empathy towards their partners would be reflected by physiological arousal (as measured by SCL and IBI) and relationship satisfaction, such that higher levels of empathy would be linked to changes in physiological arousal and higher relationship satisfaction. Further, we hypothesized that differences would be found in physiological arousal (as measured by SCL and IBI) based on the type of conflict resolution strategy used by participants. Finally, we hypothesized that differences would be found in empathy towards partner and relationship satisfaction based on the type of conflict resolution strategies used by participants. Results partially supported hypotheses and were discussed in light of existing knowledge based on empirical and theoretical sources. PMID- 24213480 TI - Reversal of hyperglycemia in diabetic mice by a marginal islet mass together with human blood outgrowth endothelial cells is independent of the delivery technique and blood clot-induced processes. AB - We recently reported that human blood outgrowth endothelial cells (BOEC) are supportive to reverse hyperglycemia in marginal islet mass-transplanted diabetic mice. In this report, we investigated whether the observed effect was evoked by islet packing in a blood clot prior to transplantation or could be mimicked by another method of islet/cell delivery. A marginal islet mass with or without BOEC was grafted underneath the kidney capsule of diabetic recipient mice via a (blood clot-independent) tubing system and compared with previous islet packing in a blood clot. The effect on metabolic outcome of both delivery techniques as well as the additive effect of BOEC was subsequently evaluated. Marginal islet mass transplantation via a tubing system required more islets per recipient than via a blood clot. Using the tubing method, transplantation of a marginal islet mass combined with 5x10 (5) BOEC resulted in reversal of hyperglycemia, improved glucose tolerance and increased kidney insulin content. The present study provides evidence that (1) previous packing in a blood clot results in more effective islet delivery compared with tubing; (2) BOEC exert a beneficial effect on marginal islet transplantation, independent of grafting technique and potential blood clot-induced processes. These data further support the use of BOEC in (pre-) clinical studies that aim to improve current islet transplantation protocols. PMID- 24213482 TI - A newborn with widespread skin lesions and extremity anomalies. AB - A variety of diseases can cause vesicular or pustular eruptions in newborns. A thorough clinical history and physical exam provide important clues for differential diagnosis. Goltz syndrome, also known as focal dermal hypoplasia, is a rare genodermatosis and generally diagnosed by the presence of the characteristic skin lesions. We present an infant with aplasia cutis, atrophic skin lesions, syndactyly and eye abnormalities who was diagnosed with Goltz syndrome soon after birth. Goltz syndrome should be considered in differential diagnosis of hypoplastic or aplastic skin lesions in neonates in the presence of skeletal or ophthalmic anomalies. PMID- 24213483 TI - Anuria in a solitary kidney with Candida bezoars managed conservatively. AB - Renal involvement is regularly encountered in neonates with invasive candidiasis, especially when risk factors like congenital malformations of the renal tract or poor bladder emptying and preterm birth are present. However, complete obstruction of the renal collecting system by fungal balls is rare. Although conservative management has been advocated for partial obstruction, complete obstruction is considered an indication for surgical drainage. We report a patient with anuria and Candida albicans bezoars in a solitary kidney, suggesting post-renal acute kidney injury. The patient was treated with systemic fluconazole and peritoneal dialysis for 4 days. The fungus balls disappeared and renal function recovered. CONCLUSION: Systemic antifungal therapy leads to clearance of obstructing fungus balls, and nephrostomy should be reserved for anuria due to bilateral complete obstruction with severe hydronephrosis. In these cases, temporary dialysis is a potential alternative. PMID- 24213484 TI - Genetic transformation of sweet potato by particle bombardment. AB - Transient and stable expression of foreign genes has been achieved in sweet potato using the particle bombardment system of gene delivery. Callus and root isolates of two genotypes (Jewel and TIS-70357) with positive signs of transformation have been recovered. Tungsten microcarriers coated with plasmid DNA (pBI 221 containing the gusA gene) were accelerated at high velocity using a biolistic device into sweet potato target tissues. Histochemical examination of bombarded leaf and petiole explants revealed that most had cells expressing the gusA gene. When explants were cultured, calli and roots developed in most bombarded tissues. Similar results but with a lower frequency of transformation were observed when the plasmid pBI 121 (with gusA and antibiotic resistance npt II genes) was employed and bombarded explants cultured on an antibiotic selection medium. Subcultured roots and calli were positive for gusA expression when tested even after one year of in vitro culture, and thus the expression of the foreign gene is fairly stable. The particle bombardment approach of gene delivery appears to have a potential for generating transgenic sweet potatoes with useful agronomic traits. PMID- 24213485 TI - Shoot regeneration from spinach hypocotyl segments by short term treatment with 5,6-dichloro-indole-3-acetic acid. AB - Factors affecting shoot regeneration from hypocotyl segments of spinach (Spinacia oleracea L.) were investigated. When expiants were cultured on medium containing 10 mg/l IAA for 7 weeks, 3 out of 9 cultivars showed relatively high shoot regeneration response (15 - 35%). The other PGRs tested had no effect on shoot regeneration. However, the transfer of explants from auxin-containing medium to auxin-free medium 20 d after culture induced shoot formation from expiants cultured on media containing each of the auxin sources tested individually. By applying this short term auxin treatment, more than 80% shoot regeneration was obtained on medium containing 5-20 mg/l 5,6-Cl2-IAA, compared to less than 30% with 10-20 mg/l IAA treatment. PMID- 24213486 TI - Promotion of plantlet formation from somatic embryos of carrot treated with a high molecular weight extract from a marine cyanobacterium. AB - Somatic embryos of Daucus carota L. developed into plantlets at high frequency after addition of an extract from a marine cyanobacterium, Synechococcus sp. NKBG 042902. High molecular weight, nondialyzing fraction, separated from the extract, possessed enhanced plantlet formation promoting activity. Plantlet formation frequency was 60 % after addition of nondialysate (100 mg/l) compared to 28 % without addition. Embryos treated with the nondialysate contained five times more chlorophyll than nontreated embryos after 6 days of culture. The chlorophyll a/b ratio of 4-day old treated somatic embryos was found to be similar to that of zygotic embryos. However, the chlorophyll a/b ratio of plantlets induced from nontreated somatic embryos was variable. Nondialysate was fractionated by ultracentrifugation and an active component obtained, which gave a maximum plantlet formation frequency of 71 %, and induced rapid greening of shoots. PMID- 24213487 TI - Tissue culture of endod (Phytolacca dodecandra L'Herit): growth and production of ribosome-inactivating proteins. AB - Leaves and stems from endod (Phytolacca dodecandra L'Herit), known to produce the 29 kDa ribosome-inactivating protein (RIP) dodecandrin, were initiated into tissue culture. Callus and suspension cultures were maintained on modified Murashige and Skoog medium plus 1.0 mg/l 2,4-dichlorophenoxyacetic acid. Six callus and two suspension cell lines were screened for dodecandrin production by western blots with affinitypurified antiserum. Antiribosomal activity of culture extracts was tested by in vitro translation assays. One suspension cell line was found to be free of immunoreactive proteins and a ribosome inhibitor. All other cell lines contain a ribosome inhibitor, although only two callus cell lines show detectable amounts of immunoreactive proteins at the same Mr as dodecandrin. Other immuno-reactive proteins were detected in callus (Mr 31000, 33000, 41000 and 43000) and in suspension cells (Mr 23000 and ~43000), and may be ribosome inhibitors related to dodecandrin-either other RIPs or dodecandrin at various stages of processing. PMID- 24213488 TI - Somatic embryogenesis and plant regeneration from leaflets of peanut, Arachis hypogaea. AB - Somatic embryos were induced on peanut (Arachis hypogaea) leaflets from aseptically germinated embryo axes. Leaflet size influenced percent somatic embryogenesis; 5-8 mm long cut leaflets were superior to 2-3 mm long uncut leaflets. Maximum embryogenesis of 14.6% was obtained after a 15 d incubation on induction medium (modified MS with B5 vitamins, 30 g/l sucrose, 4 g/l Gel-Gro, 40 mg/l 2,4-D +0.2 mg/l kinetin) followed by transfer to a secondary medium with 5 mg/l 2,4-D+0.2 mg/l kinetin. Primary somatic embryos were fused along the axes with no distinct cotyledons, but secondary embryos had single axes with two cotyledons. Other treatments had lower percent embryogenesis, no secondary embryogenesis, and embryos with single axes with two cotyledons. Some somatic embryos converted into normal plants capable of greenhouse survival. PMID- 24213489 TI - Expression of the GUS-gene in the monocot tulip after introduction by particle bombardment and Agrobacterium. AB - Gene transfer to the monocotyledon tulip (Tulipa sp. L.) was obtained both by particle bombardment and Agrobacterium transformation. Using a Particle Delivery System, transient expression of the reporter gene for betaglucuronidase was demonstrated. It was shown that the CAMV 35S as well as the TR2' promoter were active in flower stem expiants. Various wildtype and disarmed Agrobacterium strains, harbouring the 35S GUSintron gene on a binary plasmid, were used for infection of flower stem expiants of 7 cultivars and 7 botanical Tulipa species. In nine genotypes the GUSintron gene was expressed, despite the fact that tulip tissue did not produce detectable amounts of virulence-inducing substances. Agrobacterium rhizogenes appeared to be most effective in gene transfer to tulip tissue. PMID- 24213490 TI - Embryogenic cell suspensions of Triticum aestivum x Leymus angustus F1 hybrids: characterization and plant regeneration. AB - Embryogenic cell suspension cultures were established from Triticum aestivum X Leymus angustus F1 hybrids, using compact nodular calli derived from inflorescence segments. Calli originating from leaf segments did not give rise to stable cell suspensions. Growth measurements of the cell suspensions revealed that they continued rapid growth up to 10 days after subculturing. Flow cytometric studies of the cell cycle over a 7 day culture period showed that the majority of cells were in G1 phase while the rest were either in S or G2. During the 7 days of culture, no significant differences in DNA distribution patterns were observed. The cells from suspension cultures produced somatic embryos when they were transferred to different solid media. The embryos germinated and gave rise to plantlets which were successfully rooted and transferred to soil. PMID- 24213491 TI - Transient induction of tryptophan decarboxylase (TDC) and strictosidine synthase (SS) genes in cell suspension cultures of Catharanthus roseus. AB - When cell suspension cultures of Catharanthus roseus are treated with autoclaved elicitor from the fungus Pythium aphanidermatum, they respond with the rapid transient induction of tryptophan decarboxylase (TDC) and strictosidine synthase (SS) enzyme activities, followed by the accumulation of indole alkaloids (Eilert et al., 1987). In this report, we demonstrate that expression of TDC and SS enzyme activities is preceeded by the transient appearance of mRNAs for both enzymes, suggesting transcriptional control of these events. The strong transient accumulation of both TDC and SS enzyme transcripts observed in elicitor-treated cell suspension cultures contrasts with the barely detectable level of TDC transcripts and the undetectable level of SS transcripts observed in developing seedlings. PMID- 24213492 TI - Production and characterization of intergeneric somatic hybrids of Trachystoma ballii and Brassica juncea. AB - Intergeneric somatic hybrids, Trachystoma ballii (2n=16)+B. juncea (2n=38), were obtained by fusing mesophyll protoplasts of T. ballii and hypocotyl protoplasts of B. juncea using polyethylene glycol. The heterokaryotic fusion frequency was around 23%. Plants were regenerated from 10 out of 2*10(4) calli of which four were hybrids. Hybrids were intermediate between the parents in general morphology. However, in some characters one of the parents dominated. All the plants were symmetric in their chromosomal constitution as revealed by the formation of 26 bivalents at metaphase-I of meiosis. Two trivalents and 2 univalents were also observed in some pollen mother cells. Hybrid nature was also confirmed by 'Southern' hybridization of DNA of one regenerated plant restricted with Hind III and probed with the nick translated plasmid pTA71 carrying a wheat nuclear r-DNA sequence. Hybrid plant RT 1 showed bands characteristic of both parents. All the plants were absolutely pollen sterile. However, on backcrosses to B. juncea seeds were obtained. PMID- 24213493 TI - The effects of antibiotics and their breakdown products on the in vitro growth of Antirrhinum majus. AB - The effects of various antibiotics on the development of hypocotyls of Antirrhinum majus in tissue culture have been studied. The penicillins, carbenicillin and penicillin G, have been shown to stimulate callus growth, have little impact on shoot production and may stimulate root formation. The cephalosporins, cephotaxime and cephalosporin, have no effect on callus production and reduce shoot and root formation. HPLC, GC and GC-MS analyses have shown that concentrations of carbenicillin and penicillin G, commonly used in plant tissue culture, break down to give physiologically active levels of the auxin phenylacetic acid. This offers a mechanism for the stimulation of growth caused by these two antibiotics. PMID- 24213494 TI - Involvement of mixed function oxidase systems in polychlorinated biphenyl metabolism by plant cells. AB - Nineteen different polychlorinated biphenyl (PCB) congeners ranging in chlorine content from 2 to 6 chlorine atoms were provided to nonphotosynthetic suspension cultures of rose (Rosa sp. cv. Paul's Scarlet). After a 96 h incubation period, 11 individual congeners had been metabolized by > 10%. Provision of mixed function oxidase inhibitors (10 mM metyrapone or 0.5 mM 7,8-benzoflavone) either stopped or severely reduced the metabolism of individual congeners; whereas (inhibitors of peroxidase) (1 mM benzoate or 1 mM n-propylgallate) had minimal influence on PCB metabolism. The metabolism of PCBs by rose cultures appears to be catalyzed by a cytochrome P-450-and/or P-448-dependent enzyme system. PMID- 24213495 TI - Micropropagation of an elite Darjeeling tea clone. AB - Shoot cultures of Camellia sinensis (L.) O. Kuntz var. T-78, an elite Darjeeling tea clone, were established from cotyledonary nodes and shoot tips of germinated seedlings as well as from nodal explants of field grown plants. Shoot multiplication rate ranged from 4x in nodal explants to 35x in cotyledonary nodes after 18 weeks of culture. Rooting was achieved in 80-90% micro-shoots by either placing them on an inductive medium for 10 d and then transferring shoots to hormone-free medium, or by treating micro-shoots with a chronic dose of IBA (500 mg/l) for 30-40 min. Rooted plants were established in soil under glasshouse condition at 60% frequency after hardening phase of 4-6 weeks. The regenerated plants show a constant chromosome number of 2n=30 and are morphologically true to type. This procedure can be applied for conservation and utilisation of an elite clone of Darjeeling tea. PMID- 24213496 TI - Transient gene expression in strawberry (Fragaria x ananassa Duch.) protoplasts and the recovery of transgenic plants. AB - A transient beta-glucuronidase (GUS)-assay was performed to evaluate electroporation parameters and optimize DNA delivery conditions into strawberry protoplasts. Optimal GUS-activity was obtained when protoplasts were subjected to 400 V/cm for 20 ms. GUS-activity could be further increased by the addition of carrier DNA to the electroporation mixture. Callus selected on 10 MUg/ml hygromycin produced shoots which exhibited GUS-activity. The transformed nature of the shoots obtained after selection was confirmed by DNA-analysis. PMID- 24213497 TI - Estrogen signaling in lung cancer: an opportunity for novel therapy. AB - Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy. PMID- 24213499 TI - Do non-genomically encoded fusion transcripts cause recurrent chromosomal translocations? AB - We among others have recently demonstrated that normal cells produce "fusion mRNAs". These fusion mRNAs do not derive from rearranged genomic loci, but rather they are derived from "early-terminated transcripts" (ETTs). Premature transcriptional termination takes place in intronic sequences that belong to "breakpoint cluster regions". One important property of ETTs is that they exhibit an unsaturated splice donor site. This results in: (1) splicing to "cryptic exons" present in the final intron; (2) Splicing to another transcript of the same gene (intragenic trans-splicing), resulting in "exon repetitions"; (3) splicing to a transcript of another gene (intergenic trans-splicing), leading to "non-genomically encoded fusion transcripts" (NGEFTs). These NGEFTs bear the potential risk to influence DNA repair processes, since they share identical nucleotides with their DNA of origin, and thus, could be used as "guidance RNA" for DNA repair processes. Here, we present experimental data about four other genes. Three of them are associated with hemato-malignancies (ETV6, NUP98 and RUNX1), while one is associated with solid tumors (EWSR1). Our results demonstrate that all genes investigated so far (MLL, AF4, AF9, ENL, ELL, ETV6, NUP98, RUNX1 and EWSR1) display ETTs and produce transpliced mRNA species, indicating that this is a genuine property of translocating genes. PMID- 24213500 TI - High resolution fluorescence imaging of cancers using lanthanide ion-doped upconverting nanocrystals. AB - During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs), are already commercially available for this purpose. In this work we review the role which is being played by a relatively new class of nanoparticles, based on lanthanide ion doped nanocrystals, to target and image cancer cells using upconversion fluorescence microscopy. These nanoparticles are insulating nanocrystals that are usually doped with small percentages of two different rare earth (lanthanide) ions: The excited donor ions (usually Yb3+ ion) that absorb the NIR excitation and the acceptor ions (usually Er3+, Ho3+ or Tm3+), that are responsible for the emitted visible (or also near infrared) radiation. The higher conversion efficiency of these nanoparticles in respect to those based on QDs and GNRs, as well as the almost independent excitation/emission properties from the particle size, make them particularly promising for fluorescence imaging. The different approaches of these novel nanoparticles devoted to "in vitro" and "in vivo" cancer imaging, selective targeting and treatment are examined in this review. PMID- 24213498 TI - Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors. AB - Pancreatic cancer is a disease with remarkably poor patient survival rates. The frequent presence of metastases and profound chemoresistance pose a severe problem for the treatment of these tumors. Moreover, cross-talk between the tumor and the local micro-environment contributes to tumorigenicity, metastasis and chemoresistance. Compared to bulk tumor cells, cancer stem cells (CSC) have reduced sensitivity to chemotherapy. CSC are tumor cells with stem-like features that possess the ability to self-renew, but can also give rise to more differentiated progeny. CSC can be identified based on increased in vitro spheroid- or colony formation, enhanced in vivo tumor initiating potential, or expression of cell surface markers. Since CSC are thought to be required for the maintenance of a tumor cell population, these cells could possibly serve as a therapeutic target. There appears to be a causal relationship between CSC and epithelial-to-mesenchymal transition (EMT) in pancreatic tumors. The occurrence of EMT in pancreatic cancer cells is often accompanied by re-activation of developmental pathways, such as the Hedgehog, WNT, NOTCH, and Nodal/Activin pathways. Therapeutics based on CSC markers, EMT, developmental pathways, or tumor micro-environment could potentially be used to target pancreatic CSC. This may lead to a reduction of tumor growth, metastatic events, and chemoresistance in pancreatic cancer. PMID- 24213502 TI - Chemoprevention of Breast Cancer: The Paradox of Evidence versus Advocacy Inaction. AB - Women who are at high risk of breast cancer can be offered chemoprevention. Chemoprevention strategies have expanded over the past decade and include selective receptor modulator inhibitors and aromatase inhibitors. Physicians are expected to provide individualized risk assessments to identify high risk women who may be eligible for chemoprevention. It is prudent that physicians utilize a shared decision approach when counseling high risk women about their preventive options. Barriers and misperceptions however exist with patient and physician acceptance of chemoprevention and continue to impede uptake of chemoprevention as a strategy to reduce breast cancer risk. Programs to increase awareness and elucidate the barriers are critical for women to engage in cancer prevention and promote chemoprevention adherence. PMID- 24213501 TI - RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis. AB - Prostate cancer is the third leading cause of male cancer deaths in the developed world. The current lack of highly specific detection methods and efficient therapeutic agents for advanced disease have been identified as problems requiring further research. The integrins play a vital role in the cross-talk between the cell and extracellular matrix, enhancing the growth, migration, invasion and metastasis of cancer cells. Progression and metastasis of prostate adenocarcinoma is strongly associated with changes in integrin expression, notably abnormal expression and activation of the beta3 integrins in tumour cells, which promotes haematogenous spread and tumour growth in bone. As such, influencing integrin cell expression and function using targeted therapeutics represents a potential treatment for bone metastasis, the most common and debilitating complication of advanced prostate cancer. In this review, we highlight the multiple ways in which RGD-binding integrins contribute to prostate cancer progression and metastasis, and identify the rationale for development of multi-integrin antagonists targeting the RGD-binding subfamily as molecularly targeted agents for its treatment. PMID- 24213503 TI - The Development of Novel Therapies for the Treatment of Acute Myeloid Leukemia (AML). AB - Acute myeloid leukemia (AML) is nearly always a fatal malignancy. For the past 40 years, the standard of care remains a combination of cytarabine and an anthracycline known as 7 + 3. This treatment regimen is troubled by both low survival rates (10% at 5 years) and deaths due to toxicity. Substantial new laboratory findings over the past decade have identified many cellular pathways that contribute to leukemogenesis. These studies have led to the development of novel agents designed to target these pathways. Here we discuss the molecular underpinnings and clinical benefits of these novel treatment strategies. Most importantly these studies demonstrate that clinical response is best achieved by stratifying each patient based on a detailed understanding of their molecular abnormalities. PMID- 24213504 TI - Annotating cancer variants and anti-cancer therapeutics in reactome. AB - Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of "cancer" pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics. PMID- 24213505 TI - Therapeutic cancer vaccines in prostate cancer: the quest for intermediate markers of response. AB - Despite recent advances in cancer immunotherapy, no prospectively validated intermediate biomarkers exist to predict response. These biomarkers are highly desirable given modern immunotherapy's paradoxical pattern of clinical benefit; that is, improvement in overall survival without short-term change in progression. Immunotherapy clinical trials have evaluated biomarkers that may correlate with clinical outcomes. Many of them are performed on peripheral blood to evaluate the systemic response, such as tumor-targeted humoral and cellular immunity, and cytokine responses. Accumulating evidence suggests that immune infiltrates in tumors may suggest evidence for the therapy's mechanism of action, and have greater potential for providing prognostic and predictive information. In addition, a non-immunologic biomarker, such as tumor growth kinetics, may explain this paradoxical pattern of clinical benefit, and predict survival in patients treated with an immunotherapy. Prospective assessment and validation of these and other intermediate markers would be required to better understand their potential clinical role. PMID- 24213508 TI - Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells. AB - In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC50) values for Hela, SGC 7901 and BHK-21 were 15.66, 26.05 and 91.00 ug/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl 1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 MUg/mL of VCR, the respective IC50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 ug/mL, 8.43 ug/mL and 40.15 ug/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs. PMID- 24213507 TI - Nuclear DNA-Content in Mesenchymal Lesions in Dogs: Its Value as Marker of Malignancy and Extent of Genomic Instability. AB - DNA-aneuploidy may reflect the malignant nature of mesenchymal proliferations and herald gross genomic instability as a mechanistic factor in tumor genesis. DNA ploidy and -index were determined by flow cytometry in canine inflammatory or neoplastic mesenchymal tissues and related to clinico-pathological features, biological behavior and p53 gene mutational status. Half of all sarcomas were aneuploid. Benign mesenchymal neoplasms were rarely aneuploid and inflammatory lesions not at all. The aneuploidy rate was comparable to that reported for human sarcomas with significant variation amongst subtypes. DNA-ploidy status in canines lacked a relation with histological grade of malignancy, in contrast to human sarcomas. While aneuploidy was related to the development of metastases in soft tissue sarcomas it was not in osteosarcomas. No relation amongst sarcomas was found between ploidy status and presence of P53 gene mutations. Heterogeneity of the DNA index between primary and metastatic sarcoma sites was present in half of the cases examined. Hypoploidy is more common in canine sarcomas and hyperploid cases have less deviation of the DNA index than human sarcomas. The variation in the presence and extent of aneuploidy amongst sarcoma subtypes indicates variation in genomic instability. This study strengthens the concept of interspecies variation in the evolution of gross chromosomal aberrations during cancer development. PMID- 24213506 TI - Emerging Roles of ADAMTSs in Angiogenesis and Cancer. AB - A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs-ADAMTSs-are a multi-domain, secreted, extracellular zinc metalloproteinase family with 19 members in humans. These extracellular metalloproteinases are known to cleave a wide range of substrates in the extracellular matrix. They have been implicated in various physiological processes, such as extracellular matrix turnover, melanoblast development, interdigital web regression, blood coagulation, ovulation, etc. ADAMTSs are also critical in pathological processes such as arthritis, atherosclerosis, cancer, angiogenesis, wound healing, etc. In the past few years, there has been an explosion of reports concerning the role of ADAMTS family members in angiogenesis and cancer. To date, 10 out of the 19 members have been demonstrated to be involved in regulating angiogenesis and/or cancer. The mechanism involved in their regulation of angiogenesis or cancer differs among different members. Both angiogenesis-dependent and -independent regulation of cancer have been reported. This review summarizes our current understanding on the roles of ADAMTS in angiogenesis and cancer and highlights their implications in cancer therapeutic development. PMID- 24213509 TI - Immunotherapy: shifting the balance of cell-mediated immunity and suppression in human prostate cancer. AB - Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies. PMID- 24213510 TI - Induction of IL-17 producing cells and Foxp3+ regulatory T cells in areas of skin affected by localized pemphigus folliaceus. PMID- 24213511 TI - Increased serotonin transporter immunoreactivity intensity in the ileum of patients with irritable bowel disease. AB - Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, which represents an economic burden to society and considerably reduces the quality of life of patients. In a previous study, the density of serotonin cells in the ileum of IBS patients was lower compared with control subjects. The present study aimed to further investigate the immunoreactivity intensity of serotonin and serotonin-selective reuptake transporter (SERT) in the ileum of IBS patients. A total of 98 patients (77 females and 21 males; mean age, 35 years; range, 18-66 years), which fulfilled Rome III Criteria for IBS, were included in the study. This cohort included 35 patients with diarrhoea-predominant (IBS-D), 31 patients with mixed diarrhoea and constipation (M-IBS) and 32 patients with constipation-predominant (IBS-C) symptoms. A total of 27 subjects were included as controls (16 females and 11 males; mean age, 52 years; range, 20-69 years). Ileal biopsy specimens were immunostained using the avidin-biotin (ABC) complex method for serotonin and SERT. The immunoreactivity intensity was quantified by computerised image analysis using Olympus cellSens imaging software. No statistical difference of serotonin immunoreactivity intensity was identified in multiple comparisons between controls, IBS-total, IBS-D, IBS-M and IBS-C. The SERT immunoreactivity intensity was significantly increased in IBS patients as compared with controls, regardless of the subtype. It was concluded that the increase in ileal epithelial content of SERT increases the intracellular uptake of serotonin and its degradation in the gut epithelial cells and consequently decreases the availability of serotonin within the gut mucosa. The low availability of serotonin at its receptors occurred in all IBS subtypes. This may indicate that this abnormality is associated with a common symptom in all IBS subtypes, namely abdominal pain/discomfort. Serotonin acts upon sensory neurons in the submucosal and myenteric ganglia, as well as in the spinal cord, which is in agreement with this hypothesis. PMID- 24213512 TI - Evolution. PMID- 24213513 TI - The variability of lead in dusts within the homes of young children. AB - The variability of household dust lead concentration and loadings over the period of about a year has been examined in 10 homes. The overall uncertainty on a single sample is +/- 65% for lead concentration and +/- 81% for lead loading. Redecoration involving electric sanding and/or blow lamp preparation of painted surfaces is the major cause of variation in lead levels. The effect is short lived, levels returning to normal within 2 months of redecoration ending. There is evidence of a seasonal trend for dust loading and lead loading but not for lead concentration. The implications of these findings for blood lead - dust lead exposure studies are considered. PMID- 24213514 TI - Floristic variation in plant communities on metalliferous mining residues in the northern and southern Pennines, England. AB - Vegetation and soil surveys were conducted on metalliferous mine wastes in the northern and southern Pennines of England. Analyses of vegetation composition in relation to soil chemical variation were performed. Ordination analysis facilitated the detection of groups of co-occurring species which are characteristic of types of metal-contaminated soil. The results of regression analysis implied the importance of soil pH and concentration of available lead or zinc, depending upon region, in determining species distributions. A strong interactive effect was evident between soil phosphorus and zinc content in influencing species distributions in the southern Pennines sample.Regional similarities in the vegetation of apparently similar metalliferous soils existed. The unusually high species richness of some soils was associated with relatively low concentrations of heavy metals. Many species of relatively floristically-rich wastes were also colonists of surrounding grasslands or woodland. This indicated the potential importance of propagule availability and capability for rapid establishment on bare or unstable ground. Mechanisms of physiological stress avoidance, rather than heavy-metai tolerance, may explain the occurrence of non metallophytes on soils contaminated with lead and zinc. PMID- 24213515 TI - Inorganic element uptake by barley from soil supplemented with flue gas desulphurization waste and fly ash. AB - To evaluate the influence of waste products from coal- and oil-fired power plants on the inorganic element content of plants, barley was grown in pots each with 22 kg of sandy loam supplied with increasing amounts of six waste products. The plants were harvested at maturity and analysed for a number of inorganic elements. The salinity of the soil was the limiting factor for the amount added in terms of plant growth. Concerning the quality of the plants as fodder, addition of the waste to the soil at levels of about 0.5% by weight increased the Se concentration of the barley from a level deficient for animals to that approaching sufficiency for animals. The increase in Cd from the flue gas desulphurization (FGD) products was deemed undesirable, even though the concentrations following this single addition were far from toxic. All other increases in element concentrations were without any biological significance. PMID- 24213516 TI - Oxidation of sulphite originating from flue gas desulphurization waste in soil. AB - The rate of catalyzed oxidation of sulphite originating from flue gas desulphurization (FGD) waste was studied under varying conditions. The pH dependence was examined in aqueous solution at the pH range of 5 to 8, the effect of soil moisture was studied in sieved soil of different moisture contents, and the oxidation of sulphite to a soil as FGD waste, was measured at different depths in a field experiment. The experiments that the half-lives of sulphite in aqueous solution were between 0.5 and 2 hours and that the oxidation rate was highest at the lowest pH. In sieved soil the half-lives of sulphite were in the range of 3 to 20 days with the oxidation rate at the highest moisture content, indication that oxygen availability was the limiting factor. The slowest decrease of the sulphite concentration was found at a soil depth of 8-10 cm which was the where the highest background concentration of sulphite was found in control plots, too. PMID- 24213517 TI - Silver-catalyzed cascade cyclization-stannylation of o-alkynylaniline derivatives with 2-tributylstannylfuran: an efficient synthesis of (3-indolyl)stannanes. AB - A straightforward synthesis of (3-indolyl)stannanes through silver-catalyzed cyclization-stannylation of N-electron-withdrawing group-substituted o alkynylanilines in the presence of 2-tributylstannylfuran is developed. This method offers several advantages such as no requirement of additional ligands, high efficiency and a wide reaction scope. PMID- 24213518 TI - Association of cigarette smoking with the expression of nuclear survivin in pathological Stage IA lung adenocarcinomas. AB - Survivin is expressed in the cytoplasm and/or nucleus of various types of malignant tumor cells. Cytoplasmic survivin functions as an apoptosis inhibitor, while nuclear survivin is indispensable for complete mitosis completion. To investigate the effect of cigarette smoking on the survivin expression in lung adenocarcinomas at the early developmental stage, we examined the expression of nuclear and cytoplasmic survivin in pathological Stage IA lung adenocarcinomas resected from 38 non-smokers and 44 smokers (current smokers and ex-smokers) using an immunohistochemical method. Labeling indices of nuclear survivin in tumors of smokers were significantly greater than those of non-smokers. The labeling index of nuclear survivin was above 3 % in only 1 (2.6 %) of the 38 tumors of the non-smokers, while the labeling indices in 19 (43.2 %) of 44 tumors of the smokers were above 3 % with a significantly greater frequency. There was no significant difference in the labeling index of nuclear survivin between current smokers and ex-smokers. There was no significant difference in the labeling index of cytoplasmic survivin between tumors of the non-smokers and the smokers. The present results show that cigarette smoking is associated with the higher nuclear surviving expression in lung adenocarcinomas at the early stage, suggesting that cigarette smoking affects the nuclear survivin expression in lung adenocarcinomas at the early developmental stage. PMID- 24213519 TI - Solitary myofibroma of the mandible: an immunohistochemical and ultrastructural study with a review of the literature. AB - A solitary myofibroma (MF) is an unusual spindle cell neoplasm that usually arises in the soft tissue, skin, or bone of the head and neck region in infancy. We report an extremely rare case of MF of the mandible in an 18-year-old Japanese woman together with the conventional histologic, immunohistochemical, and electron microscopic findings. The tumor was well circumscribed and composed of fibroblast-like or myofibroblast-like spindle cells. On immunohistochemical evaluation the tumor cells were positive for vimentin, alpha-smooth muscle actin, HHF-35, and calponin, but negative for neurogenic antigens and markers for vascular endothelial cells. The Ki-67 labeling index was 10 % and the p53 labeling index was 10 %. Ultrastructural examination revealed smooth muscle cell differentiation. The patient was treated by surgical resection and underwent follow-up without any signs of recurrence. MF presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessarily aggressive therapy. PMID- 24213520 TI - Invasion and metastasis of renal cell carcinoma. AB - Renal cell carcinoma (RCC) represents over 80% of kidney cancer, and about 30% of the patients with RCC develop metastasis after the surgery. Invasion of basement membrane (BM) and extracellular matrix (ECM) is an essential event in tumor invasion and metastasis. Matrix metalloproteinases (MMPs), which digest the main components of BM and ECM, are expressed in RCC. Heparanase, which degrades heparan sulfate proteoglycans, is predominantly expressed in high-grade RCCs with a positive correlation with pathological tumor stage and poor prognosis. Bone metastasis is common among the patients with RCC, and increased osteoclastic activity was observed at metastatic sites. Receptor activator of nuclear factor kappaB ligand (RANKL), which plays an important role in osteoclastogenesis, is predominantly expressed in high-grade RCC and its expression level is associated with bone metastasis and prognosis. Epithelial-mesenchymal transition (EMT), a switch of epithelial cells to sarcomatoid phenotype, is considered to be critical step during metastasis, and Snail, a major regulator of EMT, is predominantly expressed in high-grade RCC, and high Snail expression is a worse prognostic factor. Accordingly, heparanase, RANKL and Snail may be targets for the development of anti-tumor therapies for RCCs. PMID- 24213521 TI - Race, ethnicity, and the duration of untreated psychosis: a systematic review. AB - PURPOSE: An extended duration of untreated psychosis (DUP) is associated with poor outcome in first-episode psychosis (FEP). Some have suggested that minority ethnic groups have longer treatment delays, and this could lead to worse outcomes. We systematically reviewed the literature on racial and ethnic differences in DUP in patients with FEP. METHODS: We searched electronic databases and conducted forward and backward tracking to identify studies that had compared DUP for people with FEP from different racial or ethnic groups. RESULTS: We identified ten papers that reported on the association between race or ethnicity and DUP. Overall, these studies did not find evidence of differences between groups; however, three of ten studies suggested that Black patients generally, and Black-African patients specifically, may have a shorter DUP relative to White patients. There were methodological limitations in most studies with respect to ethnicity classification, sample size, and adjustment for potential confounders. CONCLUSION: Racial and ethnic differences in DUP were rarely found. This could reflect that DUP does not differ between groups, or may reflect the methodological limitations of prior research. Studies that are designed and powered to examine these differences in treatment delay are needed to determine whether there are differences in DUP for minority groups. PMID- 24213522 TI - Are trauma and dissociation related to treatment resistance in patients with obsessive-compulsive disorder? AB - OBJECTIVE: Previous research has indicated a relation between obsessive compulsive disorder (OCD), childhood traumatic experiences and higher levels of dissociation that appears to relate to negative treatment outcome for OCD. The aim of the present study is to investigate whether childhood trauma and dissociation are related to severity of OCD in adulthood. We also intend to examine the association between treatment resistance, dissociation, and each form of trauma. METHODS: Participants included 120 individuals diagnosed with OCD; 58 (48.3 %) of them met the criteria for treatment-resistant OCD (resistant group), whereas the other 62 (51.7 %) were labeled as responder group. The intensity of obsessions and compulsions was evaluated using Yale-brown obsessive-compulsive scale (Y-BOCS). All patients were assessed with the traumatic experiences checklist, dissociative experiences scale, beck depression inventory, and beck anxiety inventory. RESULTS: Controlling for clinical variables, resistant group had significantly higher general OCD severity, anxiety, depression, trauma, and dissociation scores than the responders. Correlation analyses indicated that Y BOCS scores were significantly related to severity of dissociation, anxiety, depression, and traumatic experiences. In a logistic regression analysis with treatment resistance as a dependent variable, high dissociation levels, long duration of illness, and poor insight emerged as relevant predictors, but gender, levels of anxiety, depression, and traumatic experiences did not. CONCLUSIONS: Our results suggest that dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Future longitudinal studies are warranted to verify if this variable represents predictive factors of treatment non-response. PMID- 24213523 TI - Inpatient care 50 years after the process of deinstitutionalisation. AB - PURPOSE: Throughout the past 50 years mental health services have aimed to provide and improve high quality inpatient care. It is not clear whether there has been improvement as service users and nursing staff have both expressed frustration at the lack of therapeutic activities. In particular, it may be that the changing levels of symptoms over the past 50 years may affect engagement with ward activities. METHODS: Eight wards in a health care trust in London serving an inner city and urban populations participated. Data were collected on participation in activities and 116 service users' perceptions of acute care as well as clinical factors. RESULTS: Less time was spent participating in activities today than 50 years ago, while one quarter of service users reported taking part in no activities at all. Uptake of activities was related to more positive service user perceptions of the wards. Symptom severity did not impact the frequency of participation in activities, although those who took part in no activities at all had higher negative symptoms scores. CONCLUSIONS: Service users' uptake of activities was not related to the severity of their illness. This belies the belief that the acutely ill cannot take part in meaningful activities. This study supports the view that more therapeutic activities could be taken up by the acutely ill and are in fact appreciated. PMID- 24213524 TI - Commentary on suicide and homelessness: What differentiates homeless persons who died by suicide from other suicides in Australia? A comparative analysis using a unique mortality registry. PMID- 24213526 TI - Preparation and characterization of a novel Wells-Dawson heteropolyacid-based magnetic inorganic-organic nanohybrid catalyst H6P2W18O62/pyridino-Fe3O4 for the efficient synthesis of 1-amidoalkyl-2-naphthols under solvent-free conditions. AB - A novel magnetic inorganic-organic nanohybrid material H6P2W18O62/pyridino-Fe3O4 (HPA/TPI-Fe3O4) was fabricated and performed as an efficient, eco-friendly, and highly recyclable catalyst for the solvent-free, one-pot, and multi-component synthesis of various substituted 1-amidoalkyl-2-naphthols from the reaction of beta-naphthol, an aldehyde, and benzamide with good to excellent yields (47-94%) and in a short span of time (25-60 min). The nanohybrid catalyst was prepared by the chemical anchoring of Wells-Dawson heteropolyacid H6P2W18O62 onto the surface of modified Fe3O4 nanoparticles with N-[3-(triethoxysilyl)propyl]isonicotinamide (TPI) linker. The magnetically recoverable catalyst was easily recycled at least eight times without any loss of catalytic activity. XRD, TEM, UV-vis, and FTIR confirmed that the heteropolyacid H6P2W18O62 is well dispersed on the surface of the solid support and its structure is retained after immobilization on the pyridine modified Fe3O4 nanoparticles. This protocol is developed as a safe and convenient alternate method for the synthesis of 1-amidoalkyl-2-naphthols utilizing an eco-friendly, and a highly reusable catalyst. PMID- 24213525 TI - Suicidal behavior among homeless people in Japan. AB - PURPOSE: The purpose of this study is to investigate the frequency and correlates of suicidal behavior among homeless people in Japan. METHODS: A face-to-face survey was conducted in two districts of Tokyo, Japan, with 423 subjects who resided on streets and riversides and in urban parks and stations (street homeless) or who were residents of shelters, cheap hotels, or welfare homes for homeless people (sheltered homeless). RESULTS: When questioned about suicidal ideation in the previous 2 weeks, 51 subjects (12.2% of valid responses) had a recurring wish to die, 29 (6.9%) had frequent thoughts of suicide, and 22 (5.3%) had made suicide plans. In addition, 11 (2.9%) subjects had attempted suicide in the previous 2 weeks and 74 (17.7%) reported that they had ever attempted suicide. In univariate logistic regression analyses, street homelessness, lack of perceived emotional social support, poor subjective health perception, visual impairment, pain, insomnia, poor mental well-being, and current depression were significantly associated with recurrent thoughts of suicide in the previous 2 weeks. Among these, current depression had the greatest significance. In multivariate logistic regression analyses after controlling for depression, street homelessness and lack of perceived emotional social support were significantly associated with recurrent thoughts of suicide in the previous 2 weeks. CONCLUSION: Comprehensive interventions including housing and social support as well as mental health services might be crucial as effective strategies for suicide prevention among homeless people. PMID- 24213527 TI - Oncogenic deletion mutants of gp130 signal from intracellular compartments. AB - Interleukin 6 (IL-6) and, hence, activation of the IL-6 receptor signalling subunit glycoprotein 130 (gp130; also known as interleukin-6 receptor subunit beta, IL6ST), has been linked to inflammation and tumour formation. Recently, deletion mutations in gp130 have been identified in inflammatory hepatocellular adenoma. The mutations clustered around one IL-6-binding epitope and rendered gp130 constitutively active in a ligand-independent manner. Here, we show that gp130 deletion mutants, but not wild-type gp130, localise predominantly to intracellular compartments, notably the endoplasmic reticulum (ER) and early endosomes. One of the most frequent mutants, gp130 Y186-Y190del (DeltaYY) is retained in the ER quality control system because of its association with the chaperone calnexin. Furthermore, we can show that gp130 DeltaYY induces downstream signalling from both ER and endosomes, and that both signals contribute to ligand-independent cell proliferation. We also demonstrate that the endosomal localisation of gp130 DeltaYY is crucial for fully fledged STAT3 activation. Therefore, aberrant signalling from intracellular compartments might explain the tumorigenic potential of naturally occurring somatic mutations of gp130. PMID- 24213528 TI - Spire-1 contributes to the invadosome and its associated invasive properties. AB - Cancer cells have an increased ability to squeeze through extracellular matrix gaps that they create by promoting proteolysis of its components. Major sites of degradation are specialized micro-domains in the plasma membrane collectively named invadosomes where the Arp2/3 complex and formin proteins cooperate to spatio-temporally control actin nucleation and the folding of a dynamic F-actin core. At invadosomes, proper coupling of exo-endocytosis allows polarized delivery of proteases that facilitate degradation of ECM and disruption of the cellular barrier. We investigated the contribution of the actin nucleator Spire-1 to invadosome structure and function, using Src-activated cells and cancer cells. We found that Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing Src kinase, the formin mDia1 and actin. Spire 1 interacts with the Rab3A GTPase, a key player in the regulation of exocytosis that is present at invadosomes. Finally, over- and under-expression of Spire-1 resulted in cells with an increased or decreased potential for matrix degradation, respectively, therefore suggesting a functional interplay of Spire-1 with both actin nucleation and vesicular trafficking that might impact on cell invasive and metastatic behavior. PMID- 24213529 TI - Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis. AB - The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis. PMID- 24213531 TI - Osh proteins regulate COPII-mediated vesicular transport of ceramide from the endoplasmic reticulum in budding yeast. AB - Lipids synthesized at the endoplasmic reticulum (ER) are delivered to the Golgi by vesicular and non-vesicular pathways. ER-to-Golgi transport is crucial for maintaining the different membrane lipid composition and identities of organelles. Despite their importance, mechanisms regulating transport remain elusive. Here we report that in yeast coat protein complex II (COPII) vesicle mediated transport of ceramide from the ER to the Golgi requires oxysterol binding protein homologs, Osh proteins, which have been implicated in lipid homeostasis. Because Osh proteins are not required to transport proteins to the Golgi, these results indicate a specific requirement for the Osh proteins in the transport of ceramide. In addition, we provide evidence that Osh proteins play a negative role in COPII vesicle biogenesis. Together, our data suggest that ceramide transport and sphingolipid levels between the ER and Golgi are maintained by two distinct functions of Osh proteins, which negatively regulate COPII vesicle formation and positively control a later stage, presumably fusion of ceramide-enriched vesicles with Golgi compartments. PMID- 24213530 TI - Arf activation at the Golgi is modulated by feed-forward stimulation of the exchange factor GBF1. AB - ADP-ribosylation factors (Arfs) play central roles in the regulation of vesicular trafficking through the Golgi. Arfs are activated at the Golgi membrane by guanine-nucleotide-exchange factors (GEFs) that are recruited from cytosol. Here, we describe a novel mechanism for the regulation of recruitment and activity of the ArfGEF Golgi-specific BFA resistance factor 1 (GBF1). Conditions that alter the cellular Arf-GDP:Arf-GTP ratio result in GBF1 recruitment. This recruitment of GBF1 occurs selectively on cis-Golgi membranes in direct response to increased Arf-GDP. GBF1 recruitment requires Arf-GDP myristoylation-dependent interactions suggesting regulation of a membrane-bound factor. Once recruited, GBF1 causes increased Arf-GTP production at the Golgi, consistent with a feed-forward self limiting mechanism of Arf activation. This mechanism is proposed to maintain steady-state levels of Arf-GTP at the cis-Golgi during cycles of Arf-dependent trafficking events. PMID- 24213532 TI - Tumor suppressor SCUBE2 inhibits breast-cancer cell migration and invasion through the reversal of epithelial-mesenchymal transition. AB - Signal peptide-CUB-EGF domain-containing protein 2 (SCUBE2) belongs to a secreted and membrane-associated multi-domain SCUBE protein family. We previously demonstrated that SCUBE2 is a novel breast-tumor suppressor and could be a useful prognostic marker. However, the role of SCUBE2 in breast-cancer cell migration and invasion and how it is regulated during the epithelial-mesenchymal transition (EMT) remain undefined. In this study, we showed that ectopic SCUBE2 overexpression could enhance the formation of E-cadherin-containing adherens junctions by beta-catenin-SOX-mediated induction of forkhead box A1 (a positive regulator of E-cadherin) and upregulation of E-cadherin, which in turn led to epithelial transition and inhibited migration and invasion of aggressive MDA-MB 231 breast-carcinoma cells. SCUBE2 expression was repressed together with that of E-cadherin in TGF-beta-induced EMT; direct expression of SCUBE2 alone was sufficient to inhibit the TGF-beta-induced EMT. Furthermore, quantitative DNA methylation, methylation-specific PCR, and chromatin immunoprecipitation analyses revealed that SCUBE2 expression was inactivated by DNA hypermethylation at the CpG islands by recruiting and binding DNA methyltransferase 1 during TGF-beta induced EMT. Together, our results suggest that SCUBE2 plays a key role in suppressing breast-carcinoma-cell mobility and invasiveness by increasing the formation of the epithelial E-cadherin-containing adherens junctions to promote epithelial differentiation and drive the reversal of EMT. PMID- 24213533 TI - Injury-triggered Akt phosphorylation of Cx43: a ZO-1-driven molecular switch that regulates gap junction size. AB - The proteins that form vertebrate gap junctions, the connexins, are highly regulated and have short (<2 hour) half-lives. Phosphorylation of connexin43 (Cx43) affects gap junction assembly, channel gating and turnover. After finding dramatic effects on gap junctions with Akt inhibitors, we created an antibody specific for Cx43 phosphorylated on S373, a potential Akt substrate. We found S373 phosphorylation in cells and skin or heart almost exclusively in larger gap junctional structures that increased dramatically after wounding or hypoxia. We were able to mechanistically show that Akt-dependent phosphorylation of S373 increases gap junction size and communication by completely eliminating the interaction between Cx43 and ZO-1. Thus, phosphorylation on S373 acts as a molecular 'switch' to rapidly increase gap-junctional communication, potentially leading to initiation of activation and migration of keratinocytes or ischemic injury response in the skin and the heart, respectively. PMID- 24213534 TI - Specification of leading and trailing cell features during collective migration in the Drosophila trachea. AB - The role of tip and rear cells in collective migration is still a matter of debate and their differences at the cytoskeletal level are poorly understood. Here, we analysed these issues in the Drosophila trachea, an organ that develops from the collective migration of clusters of cells that respond to Branchless (Bnl), a fibroblast growth factor (FGF) homologue expressed in surrounding tissues. We track individual cells in the migratory cluster and characterise their features and unveil two prototypical types of cytoskeletal organisation that account for tip and rear cells respectively. Indeed, once the former are specified, they remain as such throughout migration. Furthermore, we show that FGF signalling in a single tip cell can trigger the migration of the cells in the branch. Finally, we found specific Rac activation at the tip cells and analysed how FGF-independent cell features, such as adhesion and motility, act on coupling the behaviour of trailing and tip cells. Thus, the combined effect of FGF promoting leading cell behaviour and the modulation of cell properties in a cluster can account for the wide range of migratory events driven by FGF. PMID- 24213535 TI - The tumor suppressor Lgl1 forms discrete complexes with NMII-A and Par6alpha aPKCzeta that are affected by Lgl1 phosphorylation. AB - Non-muscle myosin IIA (NMII-A) and the tumor suppressor lethal giant larvae 1 (Lgl1) play a central role in the polarization of migrating cells. Mammalian Lgl1 interacts directly with NMII-A, inhibiting its ability to assemble into filaments in vitro. Lgl1 also regulates the cellular localization of NMII-A, the maturation of focal adhesions and cell migration. In Drosophila, phosphorylation of Lgl affects its association with the cytoskeleton. Here we show that phosphorylation of mammalian Lgl1 by aPKCzeta prevents its interaction with NMII-A both in vitro and in vivo, and affects its inhibition of NMII-A filament assembly. Phosphorylation of Lgl1 affects its cellular localization and is important for the cellular organization of the acto-NMII cytoskeleton. We further show that Lgl1 forms two distinct complexes in vivo, Lgl1-NMIIA and Lgl1-Par6alpha aPKCzeta, and that the formation of these complexes is affected by the phosphorylation state of Lgl1. The complex Lgl1-Par6alpha-aPKCzeta resides in the leading edge of the cell. Finally, we show that aPKCzeta and NMII-A compete to bind directly to Lgl1 at the same domain. These results provide new insights into the mechanism regulating the interaction between Lgl1, NMII-A, Par6alpha and aPKCzeta in polarized migrating cells. PMID- 24213536 TI - Activated CD8(+) T cells and NKT cells in BAL fluid improve diagnostic accuracy in sarcoidosis. AB - PURPOSE: The clinical diagnosis of pulmonary sarcoidosis is based on the presence of noncaseating granulomas in an appropriate clinical setting with either bilateral hilar adenopathy and/or parenchymal infiltrates. Lymphocytosis with an increased CD4/CD8 T cell ratio in bronchoalveolar lavage fluid is supportive. We evaluated the diagnostic accuracy of a predictive binary logistic regression model in sarcoidosis based on sex, age, and bronchoalveolar lavage fluid cell profile with and without the inclusion of HLA-DR(+) CD8(+) T cells and natural killer T-cell fractions. METHODS: A retrospective analysis of differential cell counts and lymphocyte phenotypes by flow cytometry in bronchoalveolar lavage was performed in 183 patients investigated for possible diffuse parenchymal lung disease. A logistic regression model with age, sex, lymphocyte fraction, eosinophils, and CD4/CD8 ratio in bronchoalveolar lavage fluid (basic model) was compared with a final model, which also included fractions of HLA-DR(+) CD8(+) T cells and natural killer T cells. Diagnostic accuracy of the two models was assessed by receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve for the basic and final model was 0.898 [95 % confidence interval (CI) 0.852-0.945] and 0.937 (95 % CI 0.902-0.972), respectively, p = 0.008. CONCLUSIONS: Assessment of HLA-DR(+) CD8(+) T cell and natural killer T cell fractions may improve diagnostic accuracy and further strengthen the importance of bronchoalveolar lavage in the diagnostic workup of sarcoidosis. PMID- 24213537 TI - TALEN-based knockout library for human microRNAs. AB - Various technical tools have been developed to probe the functions of microRNAs (miRNAs), yet their application has been limited by low efficacy and specificity. To overcome the limitations, we used transcription activator-like effector nucleases (TALENs) to knock out human miRNA genes. We designed and produced a library of 540 pairs of TALENs for 274 miRNA loci, focusing on potentially important miRNAs. The knockout procedure takes only 2-4 weeks and can be applied to any cell type. As a case study, we generated knockout cells for two related miRNAs, miR-141 and miR-200c, which belong to the highly conserved miR-200 family. Interestingly, miR-141 and miR-200c, despite their overall similarity, suppress largely nonoverlapping groups of targets, thus suggesting that functional miRNA-target interaction requires strict seed-pairing. Our study illustrates the potency of TALEN technology and provides useful resources for miRNA research. PMID- 24213540 TI - Growth and rosmarinic acid production in cell suspension cultures of Salvia officinalis L. AB - Rosmarinic acid (RA) is a natural antioxidant produced by cell suspension cultures of sage (Salvia officinalis L.). The growth and production of RA by these cells can be modified by the type of culture medium. Production can be increased 10-fold to attain 6.4 g.1(-1) under optimal conditions. Investigation of kinetics showed that a change in the medium caused shifts in peaks of growth and production, and modifications of the cell metabolism. RA production can be correlated with growth or begins only when growth has stopped. PMID- 24213538 TI - Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges. AB - Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins. PMID- 24213541 TI - Genetic transformation of Medicago truncatula using Agrobacterium with genetically modified Ri and disarmed Ti plasmids. AB - Fertile transgenic plants of the annual pasture legume Medicago truncatula were obtained by Agrobacterium-mediated transformation, utilising a disarmed Ti plasmid and a binary vector containing the kanamycin resistance gene under the control of the cauliflower mosaic virus 35S promoter. Factors contributing to the result included an improved plant regeneration protocol and the use of explants from a plant identified as possessing high regeneration capability from tissue culture. Genes present on the T-DNA of the Ri plasmid had a negative effect on somatic embryogenesis. Only tissue inoculated with Agrobacterium strains containing a disarmed Ti plasmid lacking the T-DNA region or a Ri plasmid with an inactivated rol A gene regenerated transgenic plants. Fertile transgenic plants were only obtained with disarmed A. tumefaciens, and the introduced NPT II gene was transmitted to R1 progeny. PMID- 24213539 TI - Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography. AB - We propose an integrated method combining low-frequency mechanics with optical imaging to map the shear modulus within the biological tissue. Induced shear wave propagating in tissue is tracked in space and time using phase-sensitive optical coherence tomography (PhS-OCT). Local estimates of the shear-wave speed obtained from tracking results can image the local shear modulus. A PhS-OCT system remotely records depth-resolved, dynamic mechanical waves at an equivalent frame rate of ~47 kHz with the high spatial resolution. The proposed method was validated by examining tissue-mimicking phantoms made of agar and light scattering material. Results demonstrate that the shear wave imaging can accurately map the elastic moduli of these phantoms. PMID- 24213542 TI - Improved method for the transformation of Arabidopsis thaliana with chimeric dihydrofolate reductase constructs which confer methotrexate resistance. AB - A modified root explant transformation method has been developed that is effective in producing transgenic Arabidopsis thaliana plants which are methotrexate resistant due to the integration of T-DNA vectors containing a chimeric dihydrofolate reductase gene. Molecular analysis shows that transformed methotrexate resistant plants contain the expected T-DNA construct with the chimeric gene. This transformation method also works well with other plant selectable markers, including hygromycin phosphotransferase and neomycin phosphotransferase II. PMID- 24213543 TI - Repetitive somatic embryogenesis from peanut cultures in liquid medium. AB - A regeneration system based on repetitive somatic embryogenesis was developed for peanut (Arachis hypogaea L.). Embryogenic suspension cultures were initiated using individual somatic embryos induced from immature cotyledons cultured on a modified Murashige and Skoog medium containing 40 mg/l 2,4-D for 30 days. After transfer to a modified MS liquid medium, the somatic embryos produced masses of secondary and tertiary embryos which continued to proliferate following manual separation and subculture of the embryogenic clumps. The cultures exhibited exponential growth, and have been maintained for over one year without apparent loss of embryogenic potential. Further embryo development, germination, and conversion were achieved by placing embryo clumps onto hormone-free, solid medium. The inclusion of a desiccation period during embryo development enhanced conversion four-fold. Plants have been established in soil and appear to be phenotypically normal. PMID- 24213544 TI - In vitro micropropagation of elite rosewood (Dalbergia latifolia Roxb.). AB - Induction of single and multiple shoots was obtained from nodal expiants of 60-80 year-old elite trees of rosewood on Murashige and Skoog's basal medium supplemented with 6-benzylaminopurine (1.0 mg 1(-1)) and delta -Naphthalene acetic acid (0.05 mg 1(-1)) or indole acetic acid (0.5 mg 1(-1)). Multiplication of shoots was obtained on MS (reduced major elements) or Woody Plant Medium supplemented with 6-benzylaminopurine (1.0 mg 1(-1)) and kinetin (0.5-1.0 mg 1( 1)). Excised shoots were rooted on half-strength MS with IBA (2.0 mg 1(-1)) to obtain complete plantlets. The regenerated plantlets have been acclimatized and successfully transferred to the soil. PMID- 24213545 TI - Transformation of opium poppy (Papaver somniferum L.) with Agrobacterium rhizogenes MAFF 03-01724. AB - Transformed cultures of opium poppy (Papaver somniferum L.) were established by infecting hypocotyl segments with Agrobacterium rhizogenes MAFF 03-01724. Undifferentiated calli formed on the infected site grew satisfactorily on phytohormone-free solid medium in the dark and produced opine, mikimopine, which could not be detected in a normal culture. Numerous adventitious shoots developed from transformed calli during subculture. The transformed shoots separated individually were cultured on phytohormone-free MS solid medium at 22 degrees C under 14 h/day light. They displayed wider leaves and longer internodes than shoots established from seeds or non-transformed root culture. The content of morphinan alkaloids in the cultures and regenerated shoots were quantitatively analyzed by enzyme-linked immunosorbent assay and high performance liquid chromatography. HPLC analysis revealed that non-transformed shoots contained much more codeine (1310 gmg/g dry wt.) than morphine (50 MUg/g dry wt.), while the transformed shoot cultures did not contain morphine, although the level of morphinan alkaloids in the transformed shoots (213 MUg morphine equivalents/g fr. wt.) was comparable to that in non-transformed shoots (182 MUg morphine equivalents/g fr. wt.) by ELISA. PMID- 24213546 TI - Transgenic poplars: expression of chimeric genes using four different constructs. AB - Leaf or stem explants of a hybrid poplar clone (Populus tremula X Populus alba), sensitive to Agrobacterium tumefaciens, were co-cultivated either by an octopine or a nopaline disarmed A. tumefaciens modified strain. Transformed poplar shoots were readily regenerated from explants. The protocol was improved using the nopaline disarmed strain C58/pMP90 with the binary vector pBI121. This protocol was then used to test three other vectors. The first one, possessing a nptII gene fused to the CaMV 19S promoter, permitted regeneration of transformed shoots in presence of 50 to 100 mg/l kanamycin. The two other vectors carried an additional nptII gene under the control of the CaMV 35S or CaMV 35S promoter with a double enhancer sequence (CaMV 70). CaMV 70 promoter provided consistently higher level of gene expression than the other promoters in both callus and leaf tissues. PMID- 24213547 TI - Restoration of regeneration potential of long-term cultures of red fescue (Festuca rubra L.) by elevated sucrose levels. AB - A tissue culture protocol for restoring embryogenic ability and increasing green plant regeneration from long-term callus (5-year old) and suspension cultures of "Dawson" red fescue (Festuca rubra var trichyoplylla Gaud) was developed. Pretreatment with elevated levels of sucrose over the standard level (60 mM) enhanced regeneration capacity and decreased the number of albino plants. The highest degree of embryogenesis and green shoot number occurred when calli were pre-treated on MS basal medium supplemented with 120 mM sucrose. Mannitol caused callus discoloration and death if added to pre-treatment media at 60, 90, 120, 150 or 180 mM. Cell suspension growth was greatest when 135 mM sucrose was added to the pre-treatment growth media. High concentrations of sucrose (135 and 180 mM) were necessary for plant regeneration from suspension aggregates pretreated with 135 or 180 mM sucrose and then plated on a growth regulator-free regeneration medium composed of half-strength MS salts and B5 vitamins. PMID- 24213548 TI - A non-invasive method for the routine-estimation of fresh weight of cells grown in batch suspension cultures. AB - A simple apparatus was designed to allow sedimentation of plant cells grown in batch suspensions in Erlenmeyer flasks. After sedimentation the height of the cell mass along the glass wall was measured with a ruler fixed in the apparatus. The cell volume after sedimentation, calculated from this height, appeared highly correlated with the fresh weight of cells. This result was found with eight cell lines in two Laboratories. The method proved to be very suitable to allow routinely measurement of FW without the destruction of cells, from many samples, in a short time, during each phase of the growth cycle. PMID- 24213549 TI - High Uniformity of plants regenerated from cytogenetically variable embryogenic suspension cultures of poinsettia (Euphorbia pulcherrima Willd. ex Klotzsch). AB - Shoot tip explants, callus and embryogenic cell suspensions of Euphorbia pulcherrima have been examined for quantitative variation in nuclear DNA content by means of cytophotometry. Increasing instability was found in calli and cell suspensions from Erlenmeyer flask and bioreactor culture. Nuclear DNA content ranged from 2C up to 32 C. Plants regenerated from embryogenic cell suspensions, however, were highly uniform with regard to phenotype and ploidy level indicating strongly impaired embryogenic potential of polyploid, aneuploid or other genetically altered cells. PMID- 24213550 TI - Direct somatic embryogenesis and plant regeneration from protoplasts of Bupleurum scorzonerifolium Willd. AB - Protolasts of Bupleurum scorzonerifolium were prepared from stem node-derived embryogenic calli with an enzyeme mixture, in which snailase was a necessary component. Follolwing cell wall regeneration protoplasts divided and directly formed somatic embryos which developed into plantlets. The conditions favorable to direct embryo formation were investigated, and the nature of the callus used for protoplast preparation was found to be a critical factor. The osmotic concentration and the composition of the culture medium including the phytohormone combinations were also important. PMID- 24213551 TI - Rapid and efficient plant regeneration from hypocotyl protoplasts of Brassica carinata. AB - Protoplasts were isolated from hypocotyls of 7-d-old seedlings of three genotypes of Brassica carinata after enzymatic digestion in cellulase R-10 (0.5%) and pectolyase Y-23 (0.025%). The protoplasts were stabilized with 0.4 M mannitol used as osmoticum, and were cultured in darkness in Kao's liquid medium containing 0.4 M glucose and the growth regulators 2,4-D (1.0 mg/l), NAA (0.1 mg/l) and zeatin riboside (0.5 mg/l). Protoplasts were transferred to 16 h photoperiod conditions after 3 d of dark culture, and the medium was diluted to reduce the osmoticum on the seventh and tenth days of culture. Microcolonies were thus obtained which, upon transfer to MS agarose medium with 2,4-D (0.1 mg/l), BAP (1 mg/l) and 0.1 M sucrose, proliferated further to produce callus clumps. The plating efficiency of the three genotypes varied from 1 to 2%. Calli 2-3 mm in diameter were transferred to MS agarose plates with zeatin (2 mg/l) where they produced shoot buds and shoots with frequencies ranging from 22.5 to 74.2% for the three genotypes. The shoots were rooted in medium with IBA (1 mg/l) and were then established in soil. The time required for protoplast to plant development was 8 to 10 weeks. PMID- 24213552 TI - Somatic embryogenesis and shoot regeneration from intact seedlings of Phaseolus acutifolius A., P. aureus (L.) Wilczek, P. coccineus L., and P. wrightii L. AB - A rapid, one-step procedure has been developed for inducing direct organogenesis and somatic embryogenesis in cultures of Phaseolus coccineus L., P. acutifolius A., P. aureus L. [Vigna radiata L. Wilczek] and P. wrightii L. Development of somatic embryos and shoot buds occurred within 6-8 weeks of culture from intact seedlings raised on MS (Murashige and Skoog 1962) medium supplemented with N(6) benzylaminopurine (BAP). Shoot buds or embryoids originated from subepidermal tissue of the regions adjacent to the shoot apex, hypocotyl and cotyledonary axils. While P. acutifolius and P. aureus were regenerated via shoot formation and P. wrightii by somatic embryogenesis, both embryogenesis and shoot regeneration were observed in P. coccineus. Relatively higher levels of BAP, 50 80 MUM, were found to be optimal for inducing regeneration while lower concentrations were ineffective. About 40-70 shoots and 70-250 somatic embryos were produced per responding seedling. Regenerated shoots and somatic embryos developed into whole plants on a basal medium or the one supplemented with 1 MUM naphthaleneacetic acid. PMID- 24213553 TI - Fine mapping and epistatic interactions of the vernalization gene VRN-D4 in hexaploid wheat. AB - Wheat vernalization requirement is mainly controlled by the VRN1, VRN2, VRN3, and VRN4 genes. The first three have been cloned and have homoeologs in all three genomes. VRN4 has been found only in the D genome (VRN-D4) and has not been cloned. We constructed a high-density genetic map of the VRN-D4 region and mapped VRN-D4 within a 0.09 cM interval in the centromeric region of chromosome 5D. Using telocentric 5D chromosomes generated from the VRN-D4 donor Triple Dirk F, we determined that VRN-D4 is located on the short arm. The VRN-D4 candidate region is colinear with a 2.24 Mb region on Brachypodium distachyon chromosome 4, which includes 127 predicted genes. Ten of these genes have predicted roles in development but we detected no functional polymorphisms associated to VRN-D4. Two recombination events separated VRN-D4 from TaVIL-D1, the wheat homolog of Arabidopsis vernalization gene VIL1, confirming that this gene is not a candidate for VRN-D4. We detected significant interactions between VRN-D4 and other four genes controlling vernalization requirement (Vrn-A1, Vrn-B1, Vrn-D1, and Vrn-B3), which confirmed that VRN-D4 is part of the vernalization pathway and that it is either upstream or is part of the regulatory feedback loop involving VRN1, VRN2 and VRN3 genes. The precise mapping of VRN-D4 and the characterization of its interactions with other vernalization genes provide valuable information for the utilization of VRN-D4 in wheat improvement and for our current efforts to clone this vernalization gene. PMID- 24213555 TI - Intracortical schwannoma of the femur. AB - Schwannomas are benign nerve sheath tumors most commonly found in soft tissue. Intraosseous schwannomas are rare, and account for <0.2 % of primary bone tumors. The typical radiologic findings, a lytic lesion with a thin peripheral rim of sclerosis, are nonspecific. In all reviewed case reports, the diagnosis was made only after microscopic examination. Among previously described intraosseous schwannomas, there have been no reports of tumors arising within cortical bone. It is important to note that while schwannomas are benign tumors, they can be misdiagnosed clinically and radiographically can be potentially mistaken for metastases or other serious skeletal diseases such as osteomyelitis. Tissue sampling is critical for definitive diagnosis as well as to avoid unnecessary treatment. We present the first reported case of an intracortical schwannoma in a 42-year-old man who presented with an incidental radiographic lesion of the diaphyseal femoral cortex. PMID- 24213554 TI - Epigenomic elements enriched in the promoters of autoimmunity susceptibility genes. AB - Genome-wide association studies have identified a number of autoimmune disease susceptibility genes. Whether or not these loci share any regulatory or functional elements, however, is an open question. Finding such common regulators is of considerable research interest in order to define systemic therapeutic targets. The growing amount of experimental genomic annotations, particularly those from the ENCODE project, provide a wealth of opportunities to search for such commonalities. We hypothesized that regulatory commonalities might not only delineate a regulatory landscape predisposing to autoimmune diseases, but also define functional elements distinguishing specific diseases. We further investigated if, and how, disease-specific epigenomic elements can identify novel genes yet to be associated with the diseases. We evaluated transcription factors, histone modifications, and chromatin state data obtained from the ENCODE project for statistically significant over- or under-representation in the promoters of genes associated with Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Systemic Sclerosis (SSc). We identified BATF, BCL11A, IRF4, NFkB, PAX5, and PU.1 as transcription factors over-represented in SLE- and RA-susceptibility gene promoters. H3K4me1 and H3K4me2 epigenomic marks were associated with SLE susceptibility genes, and H3K9me3 was common to both SLE and RA. In contrast to a transcriptionally active signature in SLE and RA, SSc-susceptibility genes were depleted in activating epigenomic elements. Using epigenomic elements enriched in SLE and RA, we identified additional immune and B cell signaling-related genes with the same elements in their promoters. Our analysis suggests common and disease-specific epigenomic elements that may define novel therapeutic targets for controlling aberrant activation of autoimmune susceptibility genes. PMID- 24213556 TI - Florid osseous dysplasia with superimposed mandibular osteomyelitis. PMID- 24213557 TI - Role of phages in the epidemiology of cholera. AB - Understanding the genetic and ecological factors which support the periodic emergence of toxigenic Vibrio cholerae causing outbreaks of cholera in regions where the disease is endemic, is vital to develop preventive measures. Besides environmental factors which are not precisely defined, bacteriophages, and horizontally transmissible genetic elements are known to have a significant role in the epidemiology and evolution of the pathogen. Cholera epidemics are also known to be self-limiting, and hence identifying natural factors which contribute to the collapse of epidemics may have important implications in controlling the disease. Phages have been shown to play a crucial role in modulating cholera epidemics, and enhance V. cholerae evolution through a bactericidal selection process which favors the emergence of new clones. PMID- 24213558 TI - Kinetics of tumor destruction by chimeric antigen receptor-modified T cells. AB - The use of chimeric antigen receptor (CAR)-modified T cells as a therapy for hematologic malignancies and solid tumors is becoming more widespread. However, the infusion of a T-cell product targeting a single tumor-associated antigen may lead to target antigen modulation under this selective pressure, with subsequent tumor immune escape. With the purpose of preventing this phenomenon, we have studied the impact of simultaneously targeting two distinct antigens present on tumor cells: namely mucin 1 and prostate stem cell antigen, both of which are expressed in a variety of solid tumors, including pancreatic and prostate cancer. When used individually, CAR T cells directed against either tumor antigen were able to kill target-expressing cancer cells, but tumor heterogeneity led to immune escape. As a combination therapy, we demonstrate superior antitumor effects using both CARs simultaneously, but this was nevertheless insufficient to achieve a complete response. To understand the mechanism of escape, we studied the kinetics of T-cell killing and found that the magnitude of tumor destruction depended not only on the presence of target antigens but also on the intensity of expression-a feature that could be altered by administering epigenetic modulators that upregulated target expression and enhanced CAR T-cell potency. PMID- 24213559 TI - Bevacizumab for glioblastoma-a promising drug or not? AB - Two double blind, placebo-controlled, and randomized phase III studies were conducted, and the results including OS's were reported at the ASCO Meeting in June 2013, which was the beginning of confusion surrounding this topic. This is a review article not only summarizing the previous evidence, but also looking beyond. PMID- 24213560 TI - Axial anchoring designed silicon-porphyrin sensitizers for efficient dye sensitized solar cells. AB - Using silicon as a central atom of porphyrin allows the introduction of axial ligands, which are not only employed to prevent the aggregation of the macrocycles but also anchor the dyes onto the TiO2 surface. A dye-sensitized solar cell with this porphyrin sensitizer achieved a broad IPCE of around 40-60% between 380 and 670 nm. PMID- 24213562 TI - Mechanisms of apoptosis in irradiated and sunitinib-treated follicular thyroid cancer cells. AB - The multikinase inhibitor sunitinib (S) seems to have promising potential in the treatment of thyroid cancer. We focused on the impact of S and/or irradiation (R) on mechanisms of apoptosis in follicular thyroid cancer cells. The effects of R, S and their combination were evaluated 2 and 4 days after treatment, using the human thyroid cancer cell line CGTH W-1. The transcription of genes involved in the regulation of apoptosis was investigated using quantitative real-time PCR. Western blot analyses of caspases and survivin were also performed. S elevated BAX (day 4), CASP9, CASP3, BIRC5 (day 4) and PRKACA (day 4) gene expression, whereas the mRNAs of BCL2, CASP8, PRKCA, ERK1, and ERK2 were not significantly changed. S, R and R+S clearly induced caspase-9 protein and elevated caspase-3 activity. Survivin was down-regulated at day 4 in control cells and the expression was blunted by S treatment. R+S induced survivin expression at day 2 followed by a reduction at day 4 of treatment. Sunitinib and the combined application with radiation induced apoptosis in follicular thyroid cancer cells via the intrinsic pathway of apoptosis. In addition, sunitinib might induce apoptosis via decreased expression of the anti-apoptotic protein survivin. These findings suggest the potential use of sunitinib for the treatment of poorly differentiated follicular thyroid carcinomas. PMID- 24213561 TI - Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. AB - Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase 3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma. PMID- 24213563 TI - Interactions between SERPINA1 PiMZ genotype, occupational exposure and lung function decline. AB - OBJECTIVES: We evaluated interactions between SERPINA1 PiMZ genotype, associated with intermediate alpha1-antitrysin deficiency, with outdoor particulate matter <=10 um (PM10), and occupational exposure to vapours, dusts, gases and fumes (VGDF), and their effects on annual change in lung function. METHODS: Pre bronchodilator spirometry was performed in 3739 adults of the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) for whom SERPINA1 genotypes were available. At baseline in 1991, participants were aged 18-62 years; follow-up measurements were conducted from 2001 to 2003. In linear mixed regression models of annual change in lung function, multiplicative interactions were evaluated between PiMZ genotype (PiMM as reference) and change in PM10 (MUg/m(3)), and VGDF exposure (high-level, low-level or no exposure as reference) during follow-up. RESULTS: Annual declines in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) (-82 mL/s, 95% CI -125 to -39) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) (-0.3%, 95% CI 0.6% to 0.0%) in association with VGDF exposure were observed only in PiMZ carriers (Pinteraction<0.0001 and Pinteraction=0.03, respectively). A three-way interaction between PiMZ genotype, smoking and VGDF exposure was identified such that VGDF-associated FEF25-75% decline was observed only in ever smoking PiMZ carriers (Pinteraction=0.01). No interactions were identified between PiMZ genotype and outdoor PM10. CONCLUSIONS: SERPINA1 PiMZ genotype, in combination with smoking, modified the association between occupational VGDF exposure and longitudinal change in lung function, suggesting that interactions between these factors are relevant for lung function decline. These novel findings warrant replication in larger studies. PMID- 24213564 TI - Occupational Asthma guidelines: a systematic quality appraisal using the AGREE II instrument. AB - The quality of guidelines is often modest and highly variable. We searched the Medline database for occupational asthma (OA) guidelines meeting our inclusion criteria and undertook a systematic appraisal of them. Six appraisers independently evaluated these guidelines using the AGREE II (Appraisal of Guidelines, Research and Evaluation II) instrument. Standardised scores for each domain and for overall quality were calculated, as well as intraclass correlation coefficients to assess agreement among appraisers. Seven relevant guidelines were identified. Three were based on a systematic review of the evidence. Most guidelines scored high on the domains 'Scope and purpose' and 'Clarity and presentation', but scores on the other domains were variable. The lowest scores were for 'Applicability', suggesting that guideline developers did not pay sufficient attention to practical problems affecting the implementation of their recommendations. We also observed a trend toward improved scores in guidelines published after 2000. Inter-rater agreement was good for most domains, and particularly for 'Rigour of development'. This domain was most strongly correlated with the overall assessment scores, together with 'Scope and purpose' and 'Editorial independence'. The quality of OA guidelines is variable, both within and across guidelines. There is significant room for improvement, and greater efforts to produce high-quality guidelines are warranted, in order to assist clinical decision-making. PMID- 24213565 TI - To live or not to live near a farm? PMID- 24213566 TI - Modelling complex mixtures in epidemiologic analysis: additive versus relative measures for differential effectiveness. AB - OBJECTIVES: Mixed exposures are often combined into single exposure measures using weighting factors. This occurs for many complex mixtures in environmental and occupational epidemiology including multiple congeners, air pollutants and unique forms of ionising radiation, among others. METHODS: The weights used for combining exposures are most often determined from experimental animal and cellular research. However, evidence from observational research is necessary to support their use in risk analyses, since results from experimental research do not directly translate to observational epidemiology. RESULTS: Using simulated data, we show that ratio-based relative weights cannot be reliably estimated from observational research. As a solution to this problem, we propose an approach for estimating differences in effectiveness of distinct exposures based on their excess effectiveness compared with a reference exposure. CONCLUSIONS: This alternative is easy to calculate and provides reliable estimates of differences in effectiveness of distinct exposures. This is important to regulatory bodies using relative measures for policy decisions, as well as practicing epidemiologists conducting risk analyses. PMID- 24213567 TI - Lanthanide(III) oxalatophosphonates: syntheses, crystal structures and luminescence properties. AB - By the introduction of oxalate as the second ligand, five new lanthanide oxalatophosphonate hybrids with a 2D layered structure, namely, [Ln(H2L)(C2O4)(H2O)].2H2O [Ln = Nd (1), Sm (2), Eu (3), Tb (4), Dy (5), H3L = H2O3PCH2NCH2(CH2CH2OPO2H)], have been hydrothermally synthesized and structurally characterized by X-ray single-crystal diffraction, X-ray powder diffraction, infrared spectroscopy, elemental analysis and thermogravimetric analysis. Compounds 1-5 are isostructural and exhibit a 2D layer formed by the interconnection of a 1D zigzag chain of {Ln(C2O4)}(+) with the phosphonate ligands. The effect of lanthanide contraction induces the decrease of the lattice parameters and crystal size from Nd to Dy. The luminescence properties of compounds 2-5 have been studied. PMID- 24213568 TI - Effect of patient positioning on cerebrospinal fluid opening pressure. AB - BACKGROUND: Prone is the preferred patient position for fluoroscopic-guided lumbar puncture (LP). Normative data for cerebrospinal fluid (CSF) opening pressure (OP) exist for lateral decubitus (LD) positioning only and have not been defined for the prone position. This study compares CSF OP values in the prone and LD positions and examines the effect of body mass index (BMI) on OP. METHODS: Patients undergoing diagnostic or therapeutic fluoroscopic-guided LP were recruited prospectively at 2 tertiary care centers from 2009 to 2012. Following prone fluoroscopic-guided LP, patients were rolled to the LD position for repeat CSF OP measurement. In addition to comparing the mean OP in each position, the relationships between OP, body position, and BMI were also explored. RESULTS: Fifty-two patients were enrolled. A mean OP difference of 1.2 cm H2O was observed (prone: 26.5 cm H2O; LD: 27.7 cm H2O; P = 0.07). No correlation between CSF OP and BMI was seen in either position. CONCLUSIONS: No statistically or clinically significant difference between prone and LD OP was identified. BMI does not appear to affect CSF OP measurement in either position. PMID- 24213569 TI - Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor. AB - TAT-RasGAP(317-326), a peptide corresponding to the 317-326 sequence of p120 RasGAP coupled with a cell-permeable TAT-derived peptide, sensitizes the death response of various tumor cells to several anticancer treatments. We now report that this peptide is also able to increase cell adherence, prevent cell migration and inhibit matrix invasion. This is accompanied by a marked modification of the actin cytoskeleton and focal adhesion redistribution. Interestingly, integrins and the small Rho GTP-binding protein, which are well-characterized proteins modulating actin fibers, adhesion and migration, do not appear to be required for the pro-adhesive properties of TAT-RasGAP(317-326). In contrast, deleted in liver cancer-1, a tumor suppressor protein, the expression of which is often deregulated in cancer cells, was found to be required for TAT-RasGAP(317-326) to promote cell adherence and inhibit migration. These results show that TAT RasGAP(317-326), besides its ability to favor tumor cell death, hampers cell migration and invasion. PMID- 24213571 TI - High mobility group box 1 promotes tumor cell migration through epigenetic silencing of semaphorin 3A. AB - High mobility group box 1 (HMGB1) is a 25-kDa chromatin-associated protein that aids in transcription and DNA repair by directly binding to DNA and altering its conformation. Additionally, HMGB1 can act as an extracellular ligand. When released from dying or stressed cells, HMGB1 binds to the RAGE receptor and activates the p42/44 MAP kinase (MAPK) cascade. HMGB1 is overexpressed in many types of cancer and frequently associated with tumor stage and metastasis. This has predominantly been attributed to an autocrine function that drives MAPK pathway activity. However, by using tumor cells with activating MAPK pathway mutations, we have identified a role for HMGB1 in promoting metastasis and tumor growth that is independent of this pathway. In the absence of HMGB1, these tumor cells show defective in vitro migration as well as reduced metastasis and tumor growth in vivo despite high p42/44 phosphorylation. We found that semaphorin 3A (SEMA3A), previously shown to act as a suppressor of angiogenesis and migration, was highly increased during expression in the absence of HMGB1. SEMA3A/HMGB1 double knockdown rescued the migration defect in HMGB1 single knockdown cells. HMGB1 bound at the semaphorin 3A genomic locus, promoted hetrochromatin formation, and decreased occupancy of acetylated histones. Based on human tumor gene expression databases, HMGB1 was significantly inversely correlated with SEMA3A, suggesting that this mechanism may be more widely relevant in different cancer types. PMID- 24213570 TI - Endothelial deletion of Sag/Rbx2/Roc2 E3 ubiquitin ligase causes embryonic lethality and blocks tumor angiogenesis. AB - SAG (Sensitive to Apoptosis Gene), also known as RBX2 or ROC2, is a RING protein required for the activity of Cullin-RING ligase (CRL). Our recent study showed that Sag total knockout caused embryonic lethality at E11.5-12.5 days with associated defects in vasculogenesis. Whether Sag is required for de novo vasculogenesis in embryos and angiogenesis in tumors is totally unknown. Here, we report that Sag endothelial deletion also causes embryonic lethality at E15.5 with poor vasculogenesis. Sag deletion in primary endothelial cells (ECs) or knockdown in MS-1 ECs inhibits migration, proliferation and tube formation, with p27 accumulation being responsible for the suppression of migration and proliferation. Furthermore, Sag deletion significantly inhibits angiogenesis in an in vivo Matrigel plug assay, and tumor angiogenesis and tumorigenesis in a B16F10 melanoma model. Finally, MLN4924, an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE) that inhibits CRL, suppresses in vitro migration, proliferation and tube formation, as well as in vivo angiogenesis and tumorigenesis. Taken together, our study, using both genetic and pharmaceutical approaches, demonstrates that Sag is essential for embryonic vasculogenesis and tumor angiogenesis, and provides the proof-of-concept evidence that targeting Sag E3 ubiquitin ligase may have clinical value for anti-angiogenesis therapy of human cancer. PMID- 24213572 TI - MicroRNA-192 suppresses liver metastasis of colon cancer. AB - Metastasis causes most deaths from colon cancer yet mechanistic understanding and therapeutic options remain limited. Here we show that expression of microRNA (miR)-192 is inversely correlated with metastatic potential of colon cancer cells. Ectopic expression of miR-192 sensitizes colon cancer cells to growth factor deprivation stress-induced apoptosis, whereas inhibition of miR-192 confers resistance. Overexpression of miR-192 inhibits metastatic colonization to the liver in an orthotopic mouse model of colon cancer. Alterations associated with the metastatic phenotype in the primary tumors include increased apoptosis, decreased proliferation and angiogenesis. Further studies indicate that miR-192 downregulates expression of Bcl-2, Zeb2 and VEGFA in vitro and in vivo, which is responsible for enhanced apoptosis, increased expression of E-cadherin and decreased angiogenesis in vivo, respectively. Finally, studies performed on human colonic adenocarcinoma show that expression of miR-192 is significantly reduced in neoplastic cells as compared with normal colonic epithelium. Importantly, there is a significant decrease in miR-192 expression in stage IV tumors when compared with stage I or II lesions. These findings indicate that miR-192 has an important role in colon cancer development and progression. Our studies underscore the clinical relevance and prognostic significance of miR-192 expression in colon cancer. Therefore, a major implication of our studies is that restoration of miR-192 expression or antagonism of its target genes (Bcl-2, Zeb2 or VEGFA) may have considerable therapeutic potential for anti-metastatic therapy in patients with colon cancer. PMID- 24213574 TI - Synergistic function of Kras mutation and HBx in initiation and progression of hepatocellular carcinoma in mice. AB - Although the activation of Ras pathway is frequently observed in human hepatocellular carcinoma (HCC), the in vivo role of Ras activation in HCC initiation and progression is underdetermined. To test the consequence of Kras activation in hepatocyte, we generated a hepatocyte-specific Kras(G12D) transgenic mouse strain and observed spontaneous development of HCC in these mice. Remarkably, HBV X protein (HBx) expression significantly promotes the formation and malignant progression of Kras(G12D)-driven HCC as shown with the accelerated tumor onset, the increased tumor burden and the more poorly differentiated lesions. At the cellular level, concomitant expression of Kras(G12D) and HBx results in a robust increase in hepatocellular proliferation. We reveal that the Akt, MAPK, p53 and TGF-beta pathways are deregulated in the Kras(G12D)-driven HCCs. Also, the dysregulation is more pronounced in the HCCs developed in Kras(G12D) and HBx double transgenic mice. In addition, the altered expressions of beta-catenin, CD44 and E-cadherin are only observed in the Kras(G12D) and HBx double transgenic mice. These results demonstrate a crucial role of Ras activation in hepatocellular carcinogenesis and the functional synergy between Kras(G12D) and HBx in HCC initiation and progression. The novel genetic mouse models that closely recapitulate the histopathologic progression and molecular alterations of human HCC may potentially facilitate the future therapeutic studies. PMID- 24213573 TI - Foxm1 transcription factor is required for the initiation of lung tumorigenesis by oncogenic Kras(G12D.). AB - Lung cancer is the leading cause of deaths in cancer patients in the United States. Identification of new molecular targets is clearly needed to improve therapeutic outcomes of this devastating human disease. Activating mutations in K Ras oncogene and increased expression of FOXM1 protein are associated with poor prognosis in patients with non-small-cell lung cancer. Transgenic expression of activated Kras(G12D) in mouse respiratory epithelium is sufficient to induce lung adenocarcinomas; however, transcriptional mechanisms regulated by K-Ras during the initiation of lung cancer remain poorly understood. Foxm1 transcription factor, a downstream target of K-Ras, stimulates cellular proliferation during embryogenesis, organ repair and tumor growth, but its role in tumor initiation is unknown. In the present study, we used transgenic mice expressing Kras(G12D) under control of Sftpc promoter to demonstrate that Foxm1 was induced in type II epithelial cells before the formation of lung tumors. Conditional deletion of Foxm1 from Kras(G12D)-expressing respiratory epithelium prevented the initiation of lung tumors in vivo. The loss of Foxm1 inhibited expression of K-Ras target genes critical for the nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK) pathways, including Ikbkb, Nfkb1, Nfkb2, Rela, Jnk1, N-Myc, Pttg1 and Cdkn2a. Transgenic overexpression of activated FOXM1 mutant was sufficient to induce expression of these genes in alveolar type II cells. FOXM1 directly bound to promoter regions of Ikbkb, Nfkb2, N-Myc, Pttg1 and Cdkn2a, indicating that these genes are direct FOXM1 targets. FOXM1 is required for K-Ras-mediated lung tumorigenesis by activating genes critical for the NF-kappaB and JNK pathways. PMID- 24213575 TI - Increased leukocyte survival and accelerated onset of lymphoma in the absence of MCL-1 S159-phosphorylation. AB - The antiapoptotic BCL-2 protein MCL-1, which opposes mitochondrial outer membrane permeabilization, was shown to have a crucial role in the survival of hematopoietic cells. We have previously shown that, upon loss of phosphatidylinositol 3-kinase signaling, S159 of MCL-1 is phosphorylated by glycogen synthase kinase-3 (GSK-3), earmarking MCL-1 for enhanced ubiquitylation and degradation. In this study, we introduced MCL-1(wt) or the phosphorylation deficient mutant MCL-1(S159A) in mouse BM cells, followed by adoptive transfer to recipient mice. Mice expressing MCL-1(S159A) exhibited significantly elevated white blood cell and lymphocyte counts, whereas no effect was observed on the distribution of T and B lymphocyte subsets or the numbers of monocytes, red blood cells or platelets. Expression of MCL-1(S159A) in EMU-Myc transgenic bone marrow significantly accelerated the onset of disease, and these mice displayed increased spleen weights compared with EMU-Myc/MCL-1(wt) mice. Our data demonstrate that the absence of MCL-1 S159 phosphorylation provides a survival advantage for hematopoietic cells in vivo and facilitates oncogenesis. PMID- 24213577 TI - The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx). AB - The Polycomb group (PcG) proteins regulate stem cell differentiation via the repression of gene transcription, and their deregulation has been widely implicated in cancer development. The PcG protein Enhancer of Zeste Homolog 2 (EZH2) works as a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) by methylating lysine 27 on histone H3 (H3K27me3), a hallmark of PRC2-mediated gene repression. In skeletal muscle progenitors, EZH2 prevents an unscheduled differentiation by repressing muscle-specific gene expression and is downregulated during the course of differentiation. In rhabdomyosarcoma (RMS), a pediatric soft-tissue sarcoma thought to arise from myogenic precursors, EZH2 is abnormally expressed and its downregulation in vitro leads to muscle-like differentiation of RMS cells of the embryonal variant. However, the role of EZH2 in the clinically aggressive subgroup of alveolar RMS, characterized by the expression of PAX3-FOXO1 oncoprotein, remains unknown. We show here that EZH2 depletion in these cells leads to programmed cell death. Transcriptional derepression of F-box protein 32 (FBXO32) (Atrogin1/MAFbx), a gene associated with muscle homeostasis, was evidenced in PAX3-FOXO1 RMS cells silenced for EZH2. This phenomenon was associated with reduced EZH2 occupancy and H3K27me3 levels at the FBXO32 promoter. Simultaneous knockdown of FBXO32 and EZH2 in PAX3-FOXO1 RMS cells impaired the pro-apoptotic response, whereas the overexpression of FBXO32 facilitated programmed cell death in EZH2-depleted cells. Pharmacological inhibition of EZH2 by either 3-Deazaneplanocin A or a catalytic EZH2 inhibitor mirrored the phenotypic and molecular effects of EZH2 knockdown in vitro and prevented tumor growth in vivo. Collectively, these results indicate that EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32. They also suggest that the reducing activity of EZH2 could represent a novel adjuvant strategy to eradicate high-risk PAX3-FOXO1 alveolar RMS. PMID- 24213578 TI - The PI3-kinase isoform p110delta is essential for cell transformation induced by the D816V mutant of c-Kit in a lipid-kinase-independent manner. AB - PI3-kinase has a crucial role in transformation mediated by the oncogenic c-Kit mutant D816V. In this study, we demonstrate that the c-Kit/D816V-mediated cell survival is dependent on an intact direct binding of PI3-kinase to c-Kit. However, mutation of this binding site had little effect on the PI3-kinase activity in the cells, suggesting that c-Kit/D816V-mediated cell survival is dependent on PI3-kinase but not its kinase activity. Furthermore, inhibition of the lipid kinase activity of PI3-kinase led only to a slight inhibition of cell survival. Knockdown of the predominant PI3-kinase isoform p110delta in c Kit/D816V-expressing Ba/F3 cells led to reduced cell transformation both in vitro and in vivo without affecting the overall PI3-kinase activity. This suggests that p110delta has a lipid-kinase-independent role in c-Kit/D816V-mediated cell transformation. We furthermore demonstrate that p110delta is phosphorylated at residues Y524 and S1039 and that phosphorylation requires an intact binding site for PI3-kinase in c-Kit/D816V. Overexpression of p110delta carrying the Y523F and S1038A mutations significantly reduced c-Kit/D816V-mediated cell survival and proliferation. Taken together, our results demonstrate an important lipid-kinase independent role of p110delta in c-Kit/D816V-mediated cell transformation. This furthermore suggests that p110delta could be a potential diagnostic factor and selective therapeutic target for c-Kit/D816V-expressing malignancies. PMID- 24213576 TI - PPARbeta/delta promotes HRAS-induced senescence and tumor suppression by potentiating p-ERK and repressing p-AKT signaling. AB - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits skin tumorigenesis through mechanisms that may be dependent on HRAS signaling. The present study examined the hypothesis that PPARbeta/delta promotes HRAS induced senescence resulting in suppression of tumorigenesis. PPARbeta/delta expression increased p-ERK and decreased p-AKT activity. Increased p-ERK activity results from the dampened HRAS-induced negative feedback response mediated in part through transcriptional upregulation of RAS guanyl-releasing protein 1 (RASGRP1) by PPARbeta/delta. Decreased p-AKT activity results from repression of integrin-linked kinase (ILK) and phosphoinositide-dependent protein kinase-1 (PDPK1) expression. Decreased p-AKT activity in turn promotes cellular senescence through upregulation of p53 and p27 expression. Both over-expression of RASGRP1 and shRNA-mediated knockdown of ILK partially restore cellular senescence in Pparbeta/delta-null cells. Higher PPARbeta/delta expression is also correlated with increased senescence observed in human benign neurofibromas and colon adenoma lesions in vivo. These results demonstrate that PPARbeta/delta promotes senescence to inhibit tumorigenesis and provide new mechanistic insights into HRAS-induced cellular senescence. PMID- 24213579 TI - PAG--a multipurpose transmembrane adaptor protein. AB - Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), also known as Csk-binding protein (Cbp), is a ubiquitously expressed transmembrane adaptor protein present in lipid rafts and involved in a number of signaling pathways. It helps recruit cytoplasmic C-terminal Src kinase (Csk) to lipid raft-associated Src kinases, mediates a link to actin cytoskeleton and interacts with several other important cytoplasmic and plasma membrane-associated proteins. In recent years, PAG has been implicated in various aspects of cancer cell biology. Our review covers all so far published data on this interesting protein. PMID- 24213580 TI - Mode of action of trabectedin in myxoid liposarcomas. AB - To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respectively of type I, II and III. FUS-CHOP binding to the promoters of some target genes such as Pentraxin 3 or Fibronectin 1, assessed by chromatin immunoprecipitation, was strongly reduced in the tumor 24 h after the first or the third weekly dose of trabectedin, indicating that the drug at therapeutic doses causes a detachment of the FUS-CHOP chimera from its target promoters as previously shown in vitro. Moreover, the higher sensitivity of MRCL types I and II appears to be related to a more prolonged block of the transactivating activity of the fusion protein. Doxorubicin did not affect the binding of FUS CHOP to target promoters. Histologically, the response to trabectedin in ML017 and ML015 was associated with a marked depletion of non-lipogenic tumoral cells and vascular component, as well as lipidic maturation as confirmed by PPARgamma2 expression in western Blot. By contrast, in ML004 no major changes either in the cellularity or in the amount of mature were found, and consistently PPARgamma2 was null. In conclusion, the data support the view that the selective mechanism of action of trabectedin in MRCL is specific and related to its ability to cause a functional inactivation of the oncogenic chimera with consequent derepression of the adypocytic differentiation. PMID- 24213581 TI - Semaphorin receptors meet receptor tyrosine kinases on the way of tumor progression. AB - Semaphorins are extracellular signals known to guide migrating cells during developmental morphogenesis and in adult tissues. Semaphorin receptors, that is plexins and neuropilins, have been found in association with diverse receptor tyrosine kinases (RTKs), such as Met, ErbB2 and VEGFR2. These receptor complexes are formed in a cell-specific manner and can mediate distinctive signalling cascades, sometimes leading to divergent functional outcomes. This is particularly intriguing in cancer, since the same semaphorin has been found to mediate either tumor-promoting or tumor-suppressing functions, depending on the cancer type and cellular context. We will therefore review the current understanding about the role of RTKs in neuropilin and plexin signalling, putatively accounting for the multifaceted role of semaphorins in cancer. PMID- 24213582 TI - PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells. AB - We analyzed a complex chromosomal translocation in a case of embryonal rhabdomyosarcoma (RMS) and showed that it generates the fusion gene PAX3 (paired box 3)-NCOA2 (nuclear receptor coactivator 2). To understand the role of this translocation in RMS tumorigenesis, we established two types of stable mouse myoblast C2C12 cell lines expressing PAX3-NCOA2 and PAX3-FOXO1A (forkhead box O1A), respectively. Compared with control cells, PAX3-NCOA2 cells grew faster, were more motile, were less anchorage dependent, progressed more quickly through the G1/S phase of cell cycle and showed greater transcriptional activation of the PAX3 consensus-binding site. However, PAX3-NCOA2 cells proliferated more slowly and differentiated more weakly than did PAX3-FOXO1A cells. Both PAX3-NCOA2 cells and PAX3-FOXO1A cells formed tumors in nude mice, although the PAX3-NCOA2-induced tumors grew more slowly. Our results may explain why NCOA2 rearrangement is mainly found in embryonal rhabdomyosarcoma, which has a better prognosis than alveolar rhabdomyosarcoma, which expresses the PAX3-FOXO1A fusion gene. These results indicate that the PAX3-NCOA2 fusion gene has a dual role in the tumorigenesis of RMS: promotion of the proliferation and inhibition of the myogenic differentiation of RMS cells. PMID- 24213583 TI - Burden of disability attributable to vertigo and dizziness in the aged: results from the KORA-Age study. AB - BACKGROUND: Complaints of vertigo and dizziness are common in primary care in the aged. They can be caused by distinct vestibular disorders, but can also be a symptom in other conditions like non-vestibular sensory loss, vascular encephalopathy or anxiety. The aim of this study was to investigate the specific contribution of vertigo and dizziness to the total burden of disability in aged persons when controlling for the presence of other health conditions. METHODS: Data originate from the MONICA/KORA study, a population-based cohort. Survivors of the original cohorts who were 65 years and older were examined by telephone interview in 2009. Disability was assessed with the Health Assessment Questionnaire. Logistic regression was used to adjust for potential confounders and additive regression to estimate the contribution of vertigo and dizziness to disability prevalence. RESULTS: Adjusted for age, sex and other chronic conditions, vertigo and dizziness were associated with disability (odds ratio 1.66, 95% confidence intervals 1.40-1.98). In both men and women between 65 and 79 years, vertigo and dizziness were among the strongest contributors to the burden of disability with a prevalence of 10.5% (6.6 to 15.1) in men and 9.0% (5.7 to 13.0) in women. In men, this effect is stable across all age-groups, whereas it decreases with age in women. CONCLUSIONS: Vertigo and dizziness independently and relevantly contribute to population-attributable disability in the aged. They are not inevitable consequences of ageing but arise from distinct disease entities. Careful management of vertigo and dizziness might increase population health and reduce disability. PMID- 24213584 TI - Potential social, economic and general health benefits of consanguineous marriage: results from the Born in Bradford cohort study. AB - BACKGROUND: More than 1 billion people live in societies where consanguineous marriages are common. When children are born to consanguineous unions, there is an increased probability of the expression of single-gene disorders with a recessive mode of inheritance. There are presumptive social benefits of consanguineous marriages reported in the literature. METHODS: The UK's Born in Bradford birth cohort study recruited 12 453 women at 26-28 weeks' gestation between 2007 and 2010. In all, 11 396 completed a questionnaire, including questions about their relationship to their baby's father. We compared Pakistani and Other ethnic groups in consanguineous relationships and Pakistani, Other and White British groups not in consanguineous relationships, calculating percentages and age-adjusted prevalence ratios (95% confidence intervals). RESULTS: In the Pakistani group, 59.3% of women (n = 3038) were blood relatives of their baby's father. Consanguinity was uncommon in the Other ethnic group (7.3%, n = 127) and rare (n = 5) in the White British group. Compared with non-consanguineous counterparts, mothers in consanguineous relationships were socially and economically disadvantaged (e.g. never employed, less likely to have higher education). The Pakistani consanguineous group's social, economic and health lifestyle circumstances were equivalent to, in some cases better than, women in non-consanguineous relationships (e.g. up-to-date in paying bills, or in disagreeing that they wished for more warmth in their marital relationship). The consanguineous relationship group had less separation/divorce. Rates of cigarette smoking during pregnancy were lower in mothers in consanguineous relationships. CONCLUSION: Debate about consanguinity should balance the potential protective effect of consanguineous relationships with established genetic risk of congenital anomaly in children. PMID- 24213585 TI - Combining employment and family in Europe: the role of family policies in health. AB - OBJECTIVES: The objectives of this study were: (i) to analyse the relationship between health status and paid working hours and household composition in the EU 27, and (ii) to examine whether patterns of association differ as a function of family policy typologies and gender. METHODS: Cross-sectional study based on data from the 5th European Working Conditions Survey of 2010. The sample included married or cohabiting employees aged 25-64 years from the EU-27 (10,482 men and 8,882 women). The dependent variables were self-perceived health status and psychological well-being. RESULTS: Irrespective of differences in family policy typologies between countries, working long hours was more common among men, and part-time work was more common among women. In Continental and Southern European countries, employment and family demands were associated with poor health status in both sexes, but more consistently among women. In Anglo-Saxon countries, the association was mainly limited to men. Finally, in Nordic and Eastern European countries, employment and family demands were largely unassociated with poor health outcomes in both sexes. CONCLUSIONS: The combination of employment and family demands is largely unassociated with health status in countries with dual earner family policy models, but is associated with poorer health outcomes in countries with market-oriented models, mainly among men. This association is more consistent among women in countries with traditional models, where males are the breadwinners and females are responsible for domestic and care work. PMID- 24213586 TI - Immunosuppression-associated eosinophilic pustular folliculitis (IS-EPF) developing after Highly Active Anti-Retroviral Therapy (HAART): the possible mechanisms through CD163+ M2 macrophages. PMID- 24213587 TI - Microarray-based identification of nerve growth-promoting genes in neurofibromatosis type I. AB - As a genetic disease, neurofibromatosis type 1 (NF1) is characterized by abnormalities in multiple tissues derived from the neural crest, including neoplasms in the ends of the limbs. The exact mechanism of nerve growth in NF1 is unclear. In the present study, the gene expression profile of nerves in healthy controls and NF1 patients with macrodactylia of the fingers or toes were analyzed in order to identify possible genes associated with nerve growth. The Whole Human Genome Microarray was selected to screen for different gene expression profiles, and the result was analyzed with Feature Extraction software. The target genes were verified at the transcriptional and translational levels by reverse transcription-polymerase chain reaction and western blotting, respectively. A common set of 28 genes were identified to be changed >5-fold in the NF1 patients compared with the healthy controls. Among them, the metastasis-associated genes, lymphocyte function-associated antigen 1, C-X-C chemokine receptor type 4 and intracellular adhesion molecule 1, and the inflammatory cytokines, interleukin (IL) 1beta, IL-6 and IL-8, were downregulated significantly. Mainly genes that changed >10-fold were analyzed in this study, and HOXC8 demonstrated activity in promoting nerve growth. Through the analysis of the mRNA expression of the nerves in the NF1 patients, target molecules contributing to nerve growth during NF1 development were investigated, which aided in improving our understanding of this disease, and may provide a novel direction for nerve repair and regeneration. PMID- 24213588 TI - Free radicals properties of gamma-irradiated penicillin-derived antibiotics: piperacillin, ampicillin, and crystalline penicillin. AB - The aim of this work was to determine the concentrations and properties of free radicals in piperacillin, ampicillin, and crystalline penicillin after gamma irradiation. The radicals were studied by electron paramagnetic resonance (EPR) spectroscopy using an X-band spectrometer (9.3 GHz). Gamma irradiation was performed at a dose of 25 kGy. One- and two-exponential functions were fitted to the experimental data, in order to assess the influence of the antibiotics' storage time on the measured EPR lines. After gamma irradiation, complex EPR lines were recorded confirming the presence of a large number of free radicals formed during the irradiation. For all tested antibiotics, concentrations of free radicals and parameters of EPR spectra changed with storage time. The results obtained demonstrate that concentration of free radicals and other spectroscopic parameters can be used to select the optimal parameters of radiation sterilization of beta-lactam antibiotics. The most important parameters are the constants tau (tau (1(A),(I)) and tau (2(A),(I))) and K (K (0(A),(I)), K (1(A),(I)), K (2(A),(I))) of the exponential functions that describe free radicals decay during samples storage. PMID- 24213590 TI - Effects of sediment containing coal ash from the Kingston ash release on embryo larval development in the fathead minnow, Pimephales promelas (Rafinesque, 1820). AB - The largest environmental release of coal ash in US history occurred in December 2008 with the failure of a retention structure at the Tennessee Valley Authority Kingston Fossil Fuel Plant in East Tennessee. A byproduct of coal-burning power plants, coal ash is enriched in metals and metalloids such as selenium and arsenic with known toxicity to fish embryonic and larval life stages. The early development of fish embryos and larvae during contact exposures to river bottom sediments containing up to 78 % coal ash from the Kingston spill was examined in 7-day laboratory tests with the fathead minnow (Pimephales promelas). No significant effects were observed in hatching success, incidences of developmental abnormalities, or embryo-larval survival. Results suggest that direct exposures to sediment containing residual coal ash from the Kingston ash release may not present a significant risk to fish eggs and larvae in waterways affected by the coal ash spill. PMID- 24213591 TI - Biological effects of pyrimethinal on aquatic worms (Tubifex tubifex) under laboratory conditions. AB - Laboratory studies were conducted to determine the effects of different concentrations of pyrimethinal on protein contents, and some oxidative stress in Tubifex tubifex after an exposure of 2, 4, and 7 days. Residues of the fungicide were followed in water and in the worms. In water, pyrimethinal concentration decreased slowly (maximum -6.4 % +/- 0.8 % after 2 days for 25 mg L(-1)). In the worms, it increased after 4 days and decreased thereafter. LC50 values were between 49.2 +/- 0.58 and 39.5 +/- 0.95 mg L(-1) depending on exposure time. The activity of catalase increased in response to the fungicide after 2 days of exposure to 25 mg L(-1) of pyrimethinal (+90 %). The highest decrease of glutathione-S-transferase activity (-29.7 %) was found after 7 days in the presence of 25 mg L(-1). PMID- 24213592 TI - Transport and redistribution of Chernobyl fallout radionuclides by fluvial processes: Some preliminary evidence. AB - Several measurements of(137)Cs concentrations in suspended sediment transported by the River Severn during the post-Chernobyl period and in recent channel and floodplain deposits along the river emphasise the potential significance of fluvial processes in the transport and concentration of fallout radionuclides. PMID- 24213593 TI - Predicting the occurrence of radon-222 in groundwater supplies. AB - The intent of this study was to develop an understanding of some of the factors that affect the concentration ol radon-222 ((222)Rn) in drinking water supplies derived from groundwater, with specific application to North Carolina. Data for this investigation were collected on a sample of 96 North Carolina public water supply wells. Water samples were collected and analyzed for(222)Rn content. Data on site geology and well characteristics (discharge, specific capacity, depth, and casing length) were obtained from existing sources. From a statistical examination of the data collected in this study, we conclude that there is a distinct and statistically significant difference in the mean(222)Rn concentrations of groundwater associated with different types of rocks. The data, however, also indicate that there is a great degree of variability in the(222)Rn concentrations of samples drawn from any giver rock type. The situation is made slightly better by introducing a second variable given as the geologic region of a water supply. A fairly surprising finding of this study is the relative insignificance of discharge, specific capacity, depth, and casing length of wells as predictors of(222)Rn concentration. The present study indicates that use of these variables as predictors does not significantly improve the likelihood of locating water supplies with elevatec(222)Rn concentrations. PMID- 24213594 TI - Sources of halogens in the environment, influences on human and animal health. AB - Of the halogens, fluorine has the highest crustal abundance (544 mg/kg) while iodine has the lowest (0.25 mg/kg), however, chlorine is by far the most abundant halogen in the cosmos. The geochemistries of the four naturally occurring halogens have some similarities with fluorine, chlorine and bromine being classified as lithophile elements while iodine is more chalcophile in nature. Bromine and iodine behave in a similar fashion in the secondary environment and could be classified as biophile elements being concentrated in organic matter. Chlorine, bromine and iodine are strongly enriched in the sea while iodine and to a lesser extent bromine are further concentrated in the marine algae.Apart from the occurrence of fluorine in fluorite (CaF2) there are few commonly occurring minerals which contain the halogens as essential constituents. In the igneous environment fluorine and chlorine tend to occupy hydroxyl lattice sites in micas, amphiboles, apatites etc., while in sediments clays can contain appreciable quantities of these elements. Bromine and iodine, however, would be unlikely to fit into the lattice sites of common rock-forming minerals.Bromine, like iodine, is probably volatilised from the marine environment and is carried on to land surfaces. This behaviour of iodine and bromine is reflected in the increased I/CI and Br/CI ratios of surface run-off in continental compared with near coastal environments.Limited information on the soil geochemistry of the halogens suggests that the soil contents of chlorine, bromine and iodine are influenced by proximity to the sea. Soil fluorine, however, is generally dependent on its content in the parent material. In some areas pollutant sources of the halogens contribute appreciably to their concentration in the environment.Iodine and chlorine are essential elements for mammals and fluorine has been shown to have beneficial effects on bone and tooth formation. However, excess quantities of dietary fluorine can be harmful. It is possible, in view of its ubiquitous occurrence in the biosphere, that bromine has a hitherto unknown function in human and animal health. PMID- 24213595 TI - Background levels of microelements in soils of Italy. AB - A systematic survey on the distribution of geochemically and texicologically relevant trace elements in the soils of Italy was carried out on 32 soil profiles, developed in different environmental and pedological conditions. The aim of this study was to collect basic information on the background levels of trace elements, their geochemical behaviour and the relationships between weathering and pedogenetic processes. The statistically processed analytical results led to the following conclusions: (i) Trace element distribution in the profiles studied is consistent with pedochemical behaviour and rock lithology. A comparison with the world soil means shows that there are no significant differences, except for those elements largely utilised in agriculture (Cu, Zn) or, because of pollution, (Pd, Cd), or natural accumulation (Ni, Cr); (ii) data processing by cluster analysis shows marked correlations between some elements, for example, Al-V, Ni-Cr, Mn-Co. Groups of geochemically homogeneous samples, which correspond to the great soil families characteristic of each pedological landscape, are also indicated; (iii) evidence of soil contamination is provided by the high levels of some elements, especially in the A horizon. Cu and Zn seem to be concentrated in the Ap horizon of cultivated soils, while Pd and Cd may be derived from the atmosphere. PMID- 24213596 TI - Using the robotic device REAplan as a valid, reliable, and sensitive tool to quantify upper limb impairments in stroke patients. AB - OBJECTIVE: To validate a protocol assessing upper limb kinematics using a planar robot among stroke patients. DESIGN: Prospective cohort study. SUBJECTS: Age matched healthy subjects (n = 25) and stroke patients (n = 25). METHODS: Various kinematic indices (n = 44) were obtained from 4 tasks performed by subjects with REAplan, a planar end-effector robotic device. The metrological properties of this protocol were studied. RESULTS: In stroke patients, 43 kinematic indices showed moderate to excellent reliability (intraclass correlation coefficients (ICC) range 0.40-0.95; and minimal detectable changes range 9.9-121.1%). In healthy subjects, 25 kinematic indices showed moderate to excellent reliability (ICC range 0.40-0.91) and 3 indices showed a laterality effect (p < 0.05). Many of these indices (27 of 44) were altered in stroke patients in comparison with healthy subjects (p < 0.05). The Box and Block test (manual dexterity) and Upper Limb Sub-score of the Fugl-Meyer Assessment (motor control) showed moderate to good correlations with, respectively, 13 and 4 indices (r > 0.40). Finally, a principal component analysis allowed the elaboration of a short version of the protocol, reducing the number of indices to 5 (i.e. Amplitude, CVstraightness, Speed Metric, CVjerk metric and CVspeed metric). CONCLUSION: This study provides a standardized, valid, reliable and sensitive protocol to quantify upper limb impairments in stroke patients, using a planar robot. PMID- 24213597 TI - Body and head tilt reveals multiple frames of reference for spatial attention. AB - Most modern theories of spatial attention suggest that it is based on a maplike representation that prioritizes information in some spatial locations over others. However, movement through space changes the relationship between what is "out there" and a person's viewpoint. Does spatial attention move with the viewer, or does it stay in environmental locations? Several recent psychophysical and neuroscience studies have attempted to address this question by probing attention following saccadic eye movements. The alignment of the head and body to the external environment in these studies, however, makes it impossible to determine whether attention is based on the viewer's location in space or on the external environment. The current study therefore introduces a head and/or body tilt through the vertical plane to dissociate viewer-centered from environment centered representations. Participants first acquired a long-lasting attentional bias to a region of the search display that was likely to contain a target. They then tilted their head or body, and the location of the spatial bias was evaluated. The results suggest that attention has both a viewer-centered component that rotates with the viewer's head and an environment-centered component that is tied to environmental locations. PMID- 24213598 TI - When crowding of crowding leads to uncrowding. AB - In object recognition, features are thought to be processed in a hierarchical fashion from low-level analysis (edges and lines) to complex figural processing (shapes and objects). Here, we show that figural processing determines low-level processing. Vernier offset discrimination strongly deteriorated when we embedded a vernier in a square. This is a classic crowding effect. Surprisingly, crowding almost disappeared when additional squares were added. We propose that figural interactions between the squares precede low-level suppression of the vernier by the single square, contrary to hierarchical models of object recognition. PMID- 24213599 TI - The role of hexokinases from grape berries (Vitis vinifera L.) in regulating the expression of cell wall invertase and sucrose synthase genes. AB - In plants, hexokinase (HXK, EC 2.7.1.1) involved in hexose phosphorylation, plays an important role in sugar sensing and signaling. In this study, we found that at Phase I of grape berry development, lower hexose (glucose or fructose) levels were concomitant with higher HXK activities and protein levels. After the onset of ripening, we demonstrated a drastic reduction in HXK activity and protein levels accompanied by a rising hexose level. Therefore, our results revealed that HXK activity and protein levels had an inverse relationship with the endogenous glucose or fructose levels during grape berry development. A 51 kDa HXK protein band was detected throughout grape berry development. In addition, HXK located in the vacuoles, cytoplasm, nucleus, proplastid, chloroplast, and mitochondrion of the berry flesh cells. During grape berry development, HXK transcriptional level changed slightly, while cell wall invertase (CWINV) and sucrose synthase (SuSy) expression was enhanced after veraison stage. Intriguingly, when sliced grape berries were incubated in different glucose solutions, CWINV and SuSy expression was repressed by glucose, and the intensity of repression depended on glucose concentration and incubation time. After sliced, grape berries were treated with different glucose analogs, CWINV and SuSy expression analyses revealed that phosphorylation of hexoses by hexokinase was an essential component in the glucose-dependent CWINV and SuSy expression. In the meantime, mannoheptulose, a specific inhibitor of hexokinase, blocked the repression induced by glucose on CWINV and SuSy expression. It suggested that HXK played a major role in regulating CWINV and SuSy expression during grape berry development. PMID- 24213600 TI - Shu1 promotes homolog bias of meiotic recombination in Saccharomyces cerevisiae. AB - Homologous recombination occurs closely between homologous chromatids with highly ordered recombinosomes through RecA homologs and mediators. The present study demonstrates this relationship during the period of "partner choice" in yeast meiotic recombination. We have examined the formation of recombination intermediates in the absence or presence of Shu1, a member of the PCSS complex, which also includes Psy3, Csm2, and Shu2. DNA physical analysis indicates that Shu1 is essential for promoting the establishment of homolog bias during meiotic homologous recombination, and the partner choice is switched by Mek1 kinase activity. Furthermore, Shu1 promotes both crossover (CO) and non-crossover (NCO) pathways of meiotic recombination. The inactivation of Mek1 kinase allows for meiotic recombination to progress efficiently, but is lost in homolog bias where most doublestrand breaks (DSBs) are repaired via stable intersister joint molecules. Moreover, the Srs2 helicase deletion cells in the budding yeast show slightly reduced COs and NCOs, and Shu1 promotes homolog bias independent of Srs2. Our findings reveal that Shu1 and Mek1 kinase activity have biochemically distinct roles in partner choice, which in turn enhances the understanding of the mechanism associated with the precondition for homolog bias. PMID- 24213601 TI - EPITRANS: a database that integrates epigenome and transcriptome data. AB - Epigenetic modifications affect gene expression and thereby govern a wide range of biological processes such as differentiation, development and tumorigenesis. Recent initiatives to define genome-wide DNA methylation and histone modification profiles by microarray and sequencing methods have led to the construction of databases. These databases are repositories for international epigenetic consortiums or provide mining results from PubMed, but do not integrate the epigenetic information with gene expression changes. In order to overcome this limitation, we constructed EPITRANS, a novel database that visualizes the relationships between gene expression and epigenetic modifications. EPITRANS uses combined analysis of epigenetic modification and gene expression to search for cell function-related epigenetic and transcriptomic alterations (Freely available on the web at http://epitrans.org ). PMID- 24213602 TI - Estrogen metabolism and breast cancer risk among postmenopausal women: a case cohort study within B~FIT. AB - Although elevated circulating estrogens are associated with increased postmenopausal breast cancer risk, less is known regarding the role of estrogen metabolism in breast carcinogenesis. We conducted a case-cohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial to assess serum estrogens and estrogen metabolites (EMs) in 407 incident breast cancer cases diagnosed during follow-up and a subcohort of 496 women. In 1992-93, women completed a baseline questionnaire and provided blood samples. Hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for geography and trial participation status, were estimated using Cox proportional hazard regression. Serum concentrations of EMs were measured by liquid chromatography-tandem mass spectrometry. EMs (quintiles, Q) were analyzed individually, as metabolic pathways (C-2, -4 or -16) and as ratios. Elevated circulating estradiol was associated with increased breast cancer risk (HRQ5vsQ1 = 1.86; 95% CI: 1.19-2.90; P trend = 0.04). An elevated ratio of the 2-hydroxylation pathway (HRQ5vsQ1 = 0.69; 95% CI: 0.46-1.05; P trend = 0.01) and 4-hydroxylation pathway (HRQ5vsQ1 = 0.61; 95% CI: 0.40-0.93; P trend = 0.004) to parent estrogens (estradiol and estrone) was inversely associated with risk. A higher ratio of the 2/16 hydroxylation pathways was associated with reduced risk (HRQ5vsQ1 = 0.60; 95% CI: 0.40-0.90; P trend = 0.002). Increased 2- or 4-hydroxylation of parent estrogens may lower risk of postmenopausal breast cancer. Analyses of metabolic pathways may help elucidate the role of estrogen metabolism in breast carcinogenesis. PMID- 24213603 TI - Defective generation and maturation of dendritic cells from monocytes in colorectal cancer patients during the course of disease. AB - Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in Western countries. Today, the role of the host's immune system in controlling the progression and spread of solid tumors is broadly established. Tumor immunosurveillance escape mechanisms, such as those involving dendritic cells (DCs), the most important antigen-presenting cells, are likewise recognized processes involved in cancer. The present study evaluates the ability of CRC patients to generate DCs in vitro from circulating monocytes at both pre- and post-operative timepoints; the results are correlated with the stage of disease to shed light on the systemic immune statuses of CRC patients. Our data showed that patients' DCs had lower co-stimulatory molecule expression and were less able to present antigens to allogeneic T cells compared to healthy controls' (HC) DCs. Furthermore altered cytokine secretion, such as increased IL-10 and reduced IL-12 and TNF-alpha, was observed. At the post-operative timepoints we observed a recovery of the patients' ability to generate immature DCs, compared to HCs, but the maturational capacity remained affected. Our study conclusively highlights the persistently impaired in vitro generation of fully mature and functional DCs, which appears to be more altered during advanced stages. This work sheds light on a dendritic cell-based tumor immune escape mechanism that could be useful for the development of more effective immunotherapeutic strategies. PMID- 24213604 TI - Impact of cold ischemia on mitochondrial function in porcine hearts and blood vessels. AB - The effects of cold storage using Custodiol(r) (Histidine-Tryptophan Ketoglutarate, HTK) or isotonic saline solution on mitochondrial function in hearts (left and rights ventricles) and various blood vessels of pigs were investigated. Hearts, saphenous veins, internal-mammary-arteries and aortas of male landrace pigs were harvested and exposed to cold ischemia in either saline or Custodiol-HTK solution. Mitochondrial function was measured in situ in permeabilized fibers by high-resolution respirometry. Mitochondrial respiratory capacities (maximal respiration rates) were similar in the right and left ventricle in controls and after 14 h of cold storage were significantly better preserved in Custodiol-HTK than in saline solution. Mitochondrial respiration rates in various blood vessels including aorta, arteries and veins were less than 5% of myocardium rates. In contrast to the pig heart, in some blood vessels, like veins, mitochondrial function remained stable even after 24 h of cold ischemia. HTK-Custodiol protection of mitochondrial function after prolonged cold ischemia was observed in the myocardium but not in blood vessels. HTK-Custodiol solution thus offers significant protection of myocardial mitochondria against cold ischemic injury and can be used as efficient preservation solution in organ transplantation but probably has no benefit for blood vessels preservation. Analysis of mitochondrial function can be used as a valuable approach for the assessment of cold ischemic injury in various tissues including pig heart and various blood vessels. PMID- 24213605 TI - Environmental pollution: a tangible risk for NAFLD pathogenesis. AB - The liver is crucial for human life, and the health of this organ often mirrors the health of the individual. The liver can be the target of several diseases, the most prevalent of which, as a consequence of development and changes in human lifestyles, is the nonalcoholic fatty liver disease (NAFLD). NAFLD is a multifactorial disease that embraces many histo-pathologic conditions and is highly linked to metabolic derangements. Technological progress and industrialization have also had the consequence of releasing pollutants in the environment, for instance pesticides or solvents, as well as by-products of discharge, such as the particulate matter. In the last decade, a growing body of evidence has emerged, shedding light on the potential impact of environmental pollutants on liver health and, in particular, on NAFLD occurrence. These contaminants have a great steatogenic potential and need to be considered as tangible NAFLD risk factors. There is an urgent need for a deeper comprehension of their molecular mechanisms of action, as well as for new lines of intervention to reduce their worldwide diffusion. This review wishes to sensitize the community to the effects of several environmental pollutants on liver health. PMID- 24213606 TI - The molecular mechanisms of zinc neurotoxicity and the pathogenesis of vascular type senile dementia. AB - Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD). We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1-7 cells) and found that carnosine (beta-alanyl histidine) and histidine (His) inhibited Zn2+-induced neuronal death. A DNA microarray analysis revealed that the expression of several genes, including metal-related genes (metallothionein and Zn transporter 1), endoplasmic reticulum (ER)-stress related genes (GADD34, GADD45, and p8), and the calcium (Ca)-related gene Arc (activity related cytoskeleton protein), were affected after Zn exposure. The co-existence of carnosine or His inhibited the expression of GADD34, p8, and Arc, although they did not influence the expression of the metal-related genes. Therefore, ER stress and the disruption of Ca homeostasis may underlie the mechanisms of Zn induced neurotoxicity, and carnosine might be a possible drug candidate for the treatment of VD. PMID- 24213607 TI - Isolation, expression, and characterization of a hydroperoxide lyase gene from cucumber. AB - A full-length cDNA coding for hydroperoxide lyase (CsHPL) was isolated from cucumber fruits of No. 26 (Southern China type) and No.14-1 (Northern China type), which differed significantly in fruit flavor. The deduced amino acid sequences of CsHPL from both lines show the same and significant similarity to known plant HPLs and contain typical conserved domains of HPLs. The recombinant CsHPL was confirmed to have 9/13-HPL enzymatic activity. Gene expression levels of CsHPL were measured in different organs, especially in fruits of different development stages of both lines. The HPL activities of fruit were identified basing on the catalytic action of crude enzyme extracts incubating with 13-HPOD (13-hydroperoxy-(9Z,12E)-octadecadienoic acid) and 13-HPOD + 9-HPOD (9 hydroperoxy-(10E,12Z)-octadecadienoic acid), and volatile reaction products were analyzed by GC-MS (gas chromatography-mass spectrometry). CsHPL gene expression in No. 26 fruit occurred earlier than that of total HPL enzyme activity and 13 HPL enzyme activity, and that in No. 14-1 fruit was consistent with total HPL enzyme activity and 9-HPL enzyme activity. 13-HPL enzyme activities decreased significantly and the 9-HPL enzyme activities increased significantly with fruit ripening in both lines, which accounted for the higher content of C6 aldehydes at 0-6 day post-anthesis (dpa) and higher content of C9 aldehydes at 9-12 dpa. PMID- 24213608 TI - SEPT12-microtubule complexes are required for sperm head and tail formation. AB - The septin gene belongs to a highly conserved family of polymerizing GTP-binding cytoskeletal proteins. SEPTs perform cytoskeletal remodeling, cell polarity, mitosis, and vesicle trafficking by interacting with various cytoskeletons. Our previous studies have indicated that SEPTIN12+/+/+/- chimeras with a SEPTIN12 mutant allele were infertile. Spermatozoa from the vas deferens of chimeric mice indicated an abnormal sperm morphology, decreased sperm count, and immotile sperm. Mutations and genetic variants of SEPTIN12 in infertility cases also caused oligozoospermia and teratozoospermia. We suggest that a loss of SEPT12 affects the biological function of microtublin functions and causes spermiogenesis defects. In the cell model, SEPT12 interacts with alpha- and beta tubulins by co-immunoprecipitation (co-IP). To determine the precise localization and interactions between SEPT12 and alpha- and beta-tubulins in vivo, we created SEPTIN12-transgene mice. We demonstrate how SEPT12 interacts and co-localizes with alpha- and beta-tubulins during spermiogenesis in these mice. By using shRNA, the loss of SEPT12 transcripts disrupts alpha- and beta-tubulin organization. In addition, losing or decreasing SEPT12 disturbs the morphogenesis of sperm heads and the elongation of sperm tails, the steps of which are coordinated and constructed by alpha- and beta-tubulins, in SEPTIN12+/+/+/- chimeras. In this study, we discovered that the SEPTIN12-microtubule complexes are critical for sperm formation during spermiogenesis. PMID- 24213609 TI - Structural and functional analysis of the related transcriptional enhancer factor 1 and NF-kappaB interaction. AB - The related transcriptional enhancer factor-1 (RTEF-1) increases gene transcription of hypoxia-inducible factor 1alpha (HIF-1alpha) and enhances angiogenesis in endothelium. Both hypoxia and inflammatory factor TNF-alpha regulate gene expression of HIF-1alpha, but how RTEF-1 and TNF-alpha coordinately regulate HIF-1alpha gene transcription is unclear. Here, we found that RTEF-1 interacts with p65 subunit of NF-kappaB, a primary mediator of TNF-alpha. RTEF-1 increased HIF-1alpha promoter activity, whereas expression of p65 subunit inhibited the stimulatory effect. By contrast, knockdown of p65 markedly enhanced RTEF-1 stimulation on the HIF-1alpha promoter activity (7-fold). A physical interaction between RTEF-1 and p65 was confirmed by coimmunoprecipitation experiments in cells and glutathione S-transferase (GST)-pull-down assays. A computational analysis of RTEF-1 crystal structures revealed that a conserved surface of RTEF-1 potentially interacts with p65 via four amino acid residues located at T347, Y349, R351, and Y352. We performed site-directed mutagenesis and GST-pull-down assays and demonstrated that Tyr352 (Y352) in RTEF-1 is a key site for the formation of RTEF-1 and p65-NF-kappaB complex. An alanine mutation at Y352 of RTEF-1 disrupted the interaction of RTEF-1 with p65. Moreover, expression of RTEF-1 decreased TNF-alpha-induced HIF-1alpha promoter activity, IL-1beta, and IL-6 mRNA levels in cells; however, the effect of RTEF-1 was largely lost when Y352 was mutated to alanine. These results indicate that RTEF-1 interacts with p65-NF-kappaB through Y352 and that they antagonize each other for HIF-1alpha transcriptional activation, suggesting a novel mechanism by which RTEF-1 regulates gene expression, linking hypoxia to inflammation. PMID- 24213610 TI - Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome. AB - Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 +/- 3 yr) and healthy controls (n = 15, 31 +/- 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 +/- 2 mmHg vs. MetSyn: 102 +/- 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ~55% lower in MetSyn at SpO2 = 80% (P < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia mediated vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor. PMID- 24213611 TI - Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction. AB - We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 +/- 6 ng/ml, n = 4, P < 0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 +/- 3% of the left ventricle at day 1 with a decrease to 20 +/- 3% at day 40 (n = 6 for each group, P < 0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n = 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions. PMID- 24213613 TI - Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium. AB - In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg.kg(-1).day(-1)) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 +/- 13.4 vs. 142.0 +/- 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 +/- 22.1 vs. 231.9 +/- 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 +/- 17.0 vs. 55.61 +/- 12.7; and pyrilamine group, 106.0 +/- 8.20 vs. 49.30 +/- 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration. PMID- 24213612 TI - Nox-derived ROS are acutely activated in pressure overload pulmonary hypertension: indications for a seminal role for mitochondrial Nox4. AB - Pulmonary arterial hypertension is a severe progressive disease with marked morbidity and high mortality in which right ventricular (RV) failure is the major cause of death. Thus knowledge of the mechanisms underlying RV failure is an area of active interest. Previous studies suggest a role of NADPH oxidase in cardiomyocyte dysfunction in the left heart. Here we postulate that acute pressure overload induced by pulmonary artery banding (PAB) leads to a Nox4 initiated increase in reactive oxygen species (ROS) in mouse RV that may lead to feed-forward induction of Nox2. To test our hypothesis, ROS production was measured in RV and left ventricle homogenates. The data show that hydrogen peroxide (H2O2), but not superoxide anion (O2(.-)), was increased in the early phases (within 6 h) of PAB in RV and that this increase was diminished by catalase and diphenyleneiodonium chloride but not by SOD, N(omega)-nitro-l arginin methyl ester, febuxostat, or indomethacin. H2O2 production in RV was not attenuated in Nox2 null mice subjected to 6 h PAB. Moreover, we observed an upregulation of Nox4 mRNA after 1 h of PAB and an increase in mitochondrial Nox4 protein 6 h post-PAB. In contrast, we observed an increase in Nox2 mRNA 1 day post-PAB. Expression of antioxidant enzymes SOD, catalase, and glutathione peroxidase did not change, but catalase activity increased 6 h post-PAB. Taken together, these findings show a role of mitochondria-localized Nox4 in the early phase of PAB and suggest an involvement of this isozyme in early ROS generation possibly contributing to progression of RV dysfunction and failure. PMID- 24213614 TI - Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework. AB - The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools. PMID- 24213615 TI - The human thoracic duct is functionally innervated by adrenergic nerves. AB - Lymphatic vessels from animals have been shown to be innervated. While morphological studies have confirmed human lymphatic vessels are innervated, functional studies supporting this are lacking. The present study demonstrates a functional innervation of the human thoracic duct (TD) that is predominantly adrenergic. TDs harvested from 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro for the functional assessment of innervation by isometric force measurements and electrical field stimulation (EFS). Electron microscopy and immunohistochemistry suggested scarce diffuse distribution of nerves in the entire vessel wall, but nerve-mediated contractions could be induced with EFS and were sensitive to the muscarinic receptor blocker atropine and the alpha adrenoceptor blocker phentolamine. The combination of phentolamine and atropine resulted in a near-complete abolishment of EFS-induced contractions. The presence of sympathetic nerves was further confirmed by contractions induced by the sympathomimetic and catecholamine-releasing agent tyramine. Reactivity to the neurotransmitters norepinephrine, substance P, neuropeptide Y, acetylcholine, and methacholine was demonstrated by exogenous application to human TD ring segments. Norepinephrine provided the most consistent responses, whereas responses to the other agonists varied. We conclude that the human TD is functionally innervated with both cholinergic and adrenergic components, with the latter of the two dominating. PMID- 24213616 TI - Individual differences in cardiac and vascular components of the pressor response to isometric handgrip exercise in humans. AB - We tested the hypotheses that, in humans, changes in cardiac output (CO) and total peripheral vascular resistance (TPR) occurring in response to isometric handgrip exercise vary considerably among individuals and that those individual differences are related to differences in muscle metaboreflex and arterial baroreflex function. Thirty-nine healthy subjects performed a 1-min isometric handgrip exercise at 50% of maximal voluntary contraction. This was followed by a 4-min postexercise muscle ischemia (PEMI) period to selectively maintain activation of the muscle metaboreflex. All subjects showed increases in arterial pressure during exercise. Interindividual coefficients of variation (CVs) for the changes in CO and TPR between rest and exercise periods (CO: 95.1% and TPR: 87.8%) were more than twofold greater than CVs for changes in mean arterial pressure (39.7%). There was a negative correlation between CO and TPR responses during exercise (r = -0.751, P < 0.01), but these CO and TPR responses correlated positively with the corresponding responses during PEMI (r = 0.568 and 0.512, respectively, P < 0.01). The CO response during exercise did not correlate with PEMI-induced changes in an index of cardiac parasympathetic tone and cardiac baroreflex sensitivity. These findings demonstrate that the changes in CO and TPR that occur in response to isometric handgrip exercise vary considerably among individuals and that the two responses have an inverse relationship. They also suggest that individual differences in components of the pressor response are attributable in part to variations in muscle metaboreflex-mediated cardioaccelerator and vasoconstrictor responses. PMID- 24213618 TI - Left ventricular energetics: new insight into the plasticity of regional contributions at rest and during exercise. AB - Although the human left ventricle (LV) operates as a functional syncytium and previous studies have reported a single value for LV stroke work at rest, more intricate plasticity of regional LV energetics may be required during enhanced cardiovascular demand. We compared kinetic energy of the LV base and apex, respectively, during ventricular contraction and relaxation at rest and during continuous and discontinuous incremental exercise. At rest, prior to both exercise trials, the accumulated kinetic energy during contraction and relaxation was significantly higher at the LV base compared with the apex (P <= 0.05). With increasing exercise intensity, kinetic energy during contraction increased significantly more at the LV base (interaction effect: P < 0.0001), while kinetic energy during relaxation increased significantly more at the apex during high intensity exercise (interaction effect: P < 0.001). Total kinetic energy produced over the entire cardiac cycle was significantly greater at the LV apex during high exercise intensities (P < 0.05). We further show that the region-specific differences in kinetic energy at rest and during exercise are explained by significantly different wall mechanics, showing heterogenic contributions from radial, circumferential, and angular components at the base and apex, respectively. In conclusion, the present findings provide unique insight into human LV function by demonstrating that within this functional syncytium, significant differences in the regional contributions of kinetic energy to overall LV work exist. Importantly, regional contributions are not fixed but highly plastic and the underpinning LV wall energetics adjust according to the prevailing cardiovascular demand. PMID- 24213617 TI - Contractile protein expression is upregulated by reactive oxygen species in aorta of Goto-Kakizaki rat. AB - Although it is known that blood vessels undergo remodeling in type 2 diabetes (T2D), the signaling pathways that underlie the structural and functional changes seen in diabetic arteries remain unclear. Our objective was to determine whether the remodeling in type 2 diabetic Goto-Kakizaki (GK) rats is evoked by elevated reactive oxygen species (ROS). Our results show that aortas from GK rats produced greater force (P < 0.05) in response to stimulation with KCl and U46619 than aortas from Wistar rats. Associated with these changes, aortic expression of contractile proteins (measured as an index of remodeling) and the microRNA (miR 145), which act to upregulate transcription of contractile protein genes, was twofold higher (P < 0.05) in GK than Wistar (age-matched control) rats, and there was a corresponding increase in ROS and decrease in nitric oxide signaling. Oral administration of the antioxidant Tempol (1 mmol/l) to Wistar and GK rats reduced (P < 0.05) myocardin and calponin expression. Tempol (1 mmol/l) decreased expression of miR-145 in Wistar and GK rat aorta. To elucidate the mechanism through which ROS increases miR-145, we measured their levels in freshly isolated aorta and cultured aortic smooth muscle cells incubated for 12 h in the presence of H2O2 (300 MUmol/l). H2O2 increased expression of miR-145, and there were corresponding nuclear increases in myocardin, a miR-145 target protein. Intriguingly, H2O2-induced expression of miR-145 was decreased by U0126 (10 MUmol/l), a MEK1/2 inhibitor, and myocardin was decreased by anti-miR-145 (50 nmol/l) and U0126 (10 MUmol/l). Our novel findings demonstrate that ROS evokes vascular wall remodeling and dysfunction by enhancing expression of contractile proteins in T2D. PMID- 24213619 TI - Impact of scar on SPECT assay of left ventricular contraction dyssynchrony. AB - PURPOSE: Many patients presently receiving cardiac resynchronization therapy (CRT) do not respond. A disproportionate number of nonresponders have ischemic cardiomyopathy, with significant left ventricular (LV) scar burden. Current selection criteria, such as electrocardiography or echocardiography, may not reliably portray the magnitude of CRT-remediable LV contraction dyssynchrony. Although phase analysis of gated single photon emission computed tomography (SPECT) image data is increasingly appreciated as a tool for quantifying dyssynchrony, its use in the setting of scar has not been adequately evaluated. METHODS: Consecutive patients with ischemic (ICM, n = 50) or nonischemic (NICM, n = 39) cardiomyopathy underwent SPECT imaging prior to receiving CRT. In each patient, phase analysis of the raw images was performed to yield a phase standard deviation (PSD), an index which varies directly with the magnitude of dyssynchrony. ICM patient image data were also reanalyzed after scarred segments were stripped away. RESULTS: Raw image analysis demonstrated that PSD was significantly larger among ICM (57 +/- 17 degrees ) than NICM (35 +/- 13 degrees , p < 0.001) patients. Among ICM patients, PSD after stripping of scarred segments was significantly decreased (40 +/- 13 degrees , p < 0.001). Signals emanating from scarred segments were of low amplitude and presented a random pattern, suggestive of noise rather than indicating contraction. CONCLUSION: PSD values may be spuriously increased by scar. These findings may be important when using SPECT in selecting ischemic cardiomyopathy patients for CRT. PMID- 24213620 TI - Retraction note: Neuroradiological advances detect abnormal neuroanatomy underlying neuropsychological impairments: the power of PET imaging. PMID- 24213622 TI - The use of barbed sutures during scoliosis fusion wound closure: a quality improvement analysis. AB - BACKGROUND: Growing evidence in the orthopaedic arthroplasty literature supports the use of running bidirectional barbed suture (barbed suture) for closure of knee arthrotomies. More rapid wound closure and suture line integrity are described as its major advantages. No studies of barbed suture for the closure of posterior spinal wounds exist. The purpose of this project is to compare wound closure times and hospital charges using traditional closure versus barbed suture closure of posterior spine wounds created during scoliosis surgery. METHODS: A quality improvement project was initiated at a single tertiary-referral children's hospital spine program evaluating traditional layered interrupted suture closure (group 1) and running bidirectional barbed suture closure (Quill SRS) (group 2). Data regarding wound closure time, length of incision, fusion levels, suture cost, and hospital charges were prospectively collected over a 1 month period. RESULTS: Ten incisions comprised group 1 and 15 comprised group 2. The average wound closure times were 29.5 and 17 minutes, respectively, P=0.006. The wound lengths between the groups were statistically comparable (P=0.15). Taking into account the wound length, the average closure time in group 1 was 1.29 cm/min compared with 1.97 cm/min in group 2 (P<0.01). When accounting for the extra cost associated with the use of barbed sutures ($62.54; P<0.0001), the impact of a more rapid closure resulted in a difference in hospital charges of $884.60 per case (P=0.0013). CONCLUSIONS: Barbed suture closure of spinal fusion incisions results in a 40% reduction in closure time, resulting in an $884.60 decrease in hospital charges related to operating room time. This may represent significant yearly cost savings in a high-volume spine fusion center and warrants further investigation comparing patient-related outcomes. SIGNIFICANCE: This quality improvement analysis provides preliminary economic justification for using barbed suture for scoliosis fusion wound closure resulting in decreased operating room times and subsequent hospital charges. LEVEL OF EVIDENCE: Level II therapeutic study, prospective nonrandomized cohort. PMID- 24213621 TI - SPECT/CT and pulmonary embolism. AB - Acute pulmonary embolism (PE) is diagnosed either by ventilation/perfusion (V/P) scintigraphy or pulmonary CT angiography (CTPA). In recent years both techniques have improved. Many nuclear medicine centres have adopted the single photon emission CT (SPECT) technique as opposed to the planar technique for diagnosing PE. SPECT has been shown to have fewer indeterminate results and a higher diagnostic value. The latest improvement is the combination of a low-dose CT scan with a V/P SPECT scan in a hybrid tomograph. In a study comparing CTPA, planar scintigraphy and SPECT alone, SPECT/CT had the best diagnostic accuracy for PE. In addition, recent developments in the CTPA technique have made it possible to image the pulmonary arteries of the lungs in one breath-hold. This development is based on the change from a single-detector to multidetector CT technology with an increase in volume coverage per rotation and faster rotation. Furthermore, the dual energy CT technique is a promising modality that can provide functional imaging in combination with anatomical information. Newer high-end CT scanners and SPECT systems are able to visualize smaller subsegmental emboli. However, consensus is lacking regarding the clinical impact and treatment. In the present review, SPECT and SPECT in combination with low-dose CT, CTPA and dual energy CT are discussed in the context of diagnosing PE. PMID- 24213624 TI - Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism. AB - BACKGROUND: Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown. METHODS: IUGR was induced through maternal dexamethasone infusion (100 MUg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pup growth was monitored, and Pup brain metabolism and gene expression were studied using in vivo (1)H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7. RESULTS: Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pups (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (gamma-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation. CONCLUSION: Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes. PMID- 24213623 TI - Gay male couples' attitudes toward using couples-based voluntary HIV counseling and testing. AB - Many men who have sex with men acquire HIV from their primary male partners while in a relationship. Studies with gay couples have demonstrated that relationship characteristics and testing behaviors are important to examine for HIV prevention. Recently, couples-based voluntary HIV counseling and testing (CVCT) has become available to male couples throughout the U.S. However, HIV-negative couples' attitudes toward using CVCT and how their relationship characteristics may affect their use of CVCT remain largely unknown. This information is particularly relevant for organizations that offer CVCT. To assess couples' attitudes, and associated factors toward using CVCT, a cross-sectional study design was used with a novel Internet-based recruitment method to collect dyadic data from a national sample of 275 HIV-negative gay couples. Multivariate multilevel modeling was used to identify factors associated with differences between and within couples about their attitudes towards using CVCT. Findings revealed that couples were "somewhat" to "very likely" to use CVCT. More positive attitudes toward using CVCT were associated with couples who had higher levels of relationship satisfaction and commitment toward their sexual agreement and among those who had at least one partner having had sex outside of the relationship. Less positive attitude toward using CVCT was associated with couples who had higher levels of trust toward their partners being dependable. Differences within couples, including age between partners, whether sex had occurred outside of the relationship, and value toward a sexual agreement also affected their attitudes toward using CVCT. Providing additional testing methods may help HIV-negative gay couples better manage their HIV risk. PMID- 24213626 TI - Shining light on integrity of a tetracobalt-polyoxometalate water oxidation catalyst by X-ray spectroscopy before and after catalysis. AB - Modification of the Co-oxo cores of cobalt-polyoxometalate water oxidation catalysts is detectable by X-ray absorption spectroscopy (XAS) as demonstrated by comparison of Na10[Co4(H2O)2(PW9O34)2] (1) and Na17[((Co(H2O))Co2PW9O34)2(PW6O26)] (2). XAS reveals the integrity of 1 uncompromised by oxidant-driven water oxidation, which proceeds without formation of catalytic cobalt oxide. PMID- 24213625 TI - Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. AB - Systemic juvenile idiopathic arthritis (s-JIA) is clinically distinct from other types of JIA. It is typified by extraarticular features such as quotidian fevers, rash, splenomegaly, lymphadenopathy, laboratory abnormalities (including leukocytosis, thrombocytosis, anemia, hyperferritinemia, and elevated inflammatory markers), and a close association with the macrophage activation syndrome. Recent investigations have highlighted dysregulation of the innate immune system as the critical pathogenic driver of s-JIA. Key innate immune mediators of s-JIA are the macrophage-derived cytokines interleukin-1 (IL-1) and IL-6. Increased understanding of the roles of IL-1 and IL-6 in the pathogenesis of s-JIA has led to major changes in therapeutic options. Until recently, the most commonly used medications included corticosteroids, methotrexate, and tumor necrosis factor (TNF) inhibitors, which are incompletely effective in most cases. Newer biologic agents targeting IL-1 and IL-6 have proven very effective in treating s-JIA and in minimizing corticosteroid exposure. Here we review recent advances in the understanding of the pathogenesis of s-JIA and the recent clinical trials that have revolutionized the care of children with s-JIA. PMID- 24213627 TI - Together but different: co-occurring dune plant species differ in their water- and nitrogen-use strategies. AB - Stress factors may severely constrain the range of plant physiological responses in harsh environments. Convergence of traits is expected in coastal dunes because of environmental filtering imposed by severe abiotic factors. However, the wide range of morphological and phenological traits exhibited by coexisting dune species suggests considerable variation in functional traits. We hypothesized that the constraints imposed by structural traits ought to translate into physiological differences. Five dominant species with different morphological traits, but coexisting in a homogeneous dune area in Northwest Spain, were selected for study. Soil characteristics and leaf functional traits were measured in April, June and November 2008. Integrated water-use efficiency (assessed by C isotope discrimination) and N acquisition and use strategies (estimated by N isotope composition) varied significantly among species and the differences changed over time. Species differences in specific leaf area, relative water content, leaf N and C:N ratio, also varied over time. The species differed in stomatal density but not in soil characteristics, with the exception of pH. Species differences in functional traits related to the use of resources suggest species niche segregation. Species-specific temporal effects on the use of these resources support temporal niche differentiation. Somewhat in contrast to the findings of previous studies on harsh environments, this study revealed a considerable level of functional diversity and complexity, suggesting that dune plant species have evolved species-specific strategies to survive by partitioning growth-limiting resources. PMID- 24213628 TI - Climate sensitivity of reproduction in a mast-seeding boreal conifer across its distributional range from lowland to treeline forests. AB - Mast-seeding conifers such as Picea glauca exhibit synchronous production of large seed crops over wide areas, suggesting climate factors as possible triggers for episodic high seed production. Rapidly changing climatic conditions may thus alter the tempo and spatial pattern of masting of dominant species with potentially far-reaching ecological consequences. Understanding the future reproductive dynamics of ecosystems including boreal forests, which may be dominated by mast-seeding species, requires identifying the specific cues that drive variation in reproductive output across landscape gradients and among years. Here we used annual data collected at three sites spanning an elevation gradient in interior Alaska, USA between 1986 and 2011 to produce the first quantitative models for climate controls over both seedfall and seed viability in P. glauca, a dominant boreal conifer. We identified positive associations between seedfall and increased summer precipitation and decreased summer warmth in all years except for the year prior to seedfall. Seed viability showed a contrasting response, with positive correlations to summer warmth in all years analyzed except for one, and an especially positive response to warm and wet conditions in the seedfall year. Finally, we found substantial reductions in reproductive potential of P. glauca at high elevation due to significantly reduced seed viability there. Our results indicate that major variation in the reproductive potential of this species may occur in different landscape positions in response to warming, with decreasing reproductive success in areas prone to drought stress contrasted with increasing success in higher elevation areas currently limited by cool summer temperatures. PMID- 24213629 TI - Effects of fire frequency and season on resprouting of woody plants in southeastern US pine-grassland communities. AB - Past studies suggest that rates of woody plant resprouting following a "topkilling" disturbance relate to timing of disturbance because of temporal patterns of below-ground carbohydrate storage. Accordingly, we hypothesized that fire-return interval (1 or 2 years) and season of burn (late dormant or early growing season) would influence the change in resprout growth rate from one fire free interval to the next (Delta growth rate) for broadleaf woody plants in a pine-grassland in Georgia, USA. Resprout growth rate during one fire-free interval strongly predicted growth rate during the following fire-free interval, presumably reflecting root biomass. Length of fire-free interval did not have a significant effect on mean Delta growth rate. Plants burned in the late dormant season (February-March) had a greater positive Delta growth rate than those burned in the early growing season (April-June), consistent with the presumption that root carbohydrates are depleted and thus limiting during spring growth. Plants with resprout growth rates above a certain level had zero or negative Delta growth rates, indicating an equilibrium of maximum resprout size under a given fire-return interval. This equilibrium, as well as relatively reduced resprout growth rate following growing season fires, provide insight into how historic lightning-initiated fires in the early growing season limited woody plant dominance and maintained the herb-dominated structure of pine-grassland communities. Results also indicate tradeoffs between applying prescribed fire at 1- versus 2-year intervals and in the dormant versus growing seasons with the goal of limiting woody vegetation. PMID- 24213630 TI - Perovskite oxides for visible-light-absorbing ferroelectric and photovoltaic materials. AB - Ferroelectrics have recently attracted attention as a candidate class of materials for use in photovoltaic devices, and for the coupling of light absorption with other functional properties. In these materials, the strong inversion symmetry breaking that is due to spontaneous electric polarization promotes the desirable separation of photo-excited carriers and allows voltages higher than the bandgap, which may enable efficiencies beyond the maximum possible in a conventional p-n junction solar cell. Ferroelectric oxides are also stable in a wide range of mechanical, chemical and thermal conditions and can be fabricated using low-cost methods such as sol-gel thin-film deposition and sputtering. Recent work has shown how a decrease in ferroelectric layer thickness and judicious engineering of domain structures and ferroelectric-electrode interfaces can greatly increase the current harvested from ferroelectric absorber materials, increasing the power conversion efficiency from about 10(-4) to about 0.5 per cent. Further improvements in photovoltaic efficiency have been inhibited by the wide bandgaps (2.7-4 electronvolts) of ferroelectric oxides, which allow the use of only 8-20 per cent of the solar spectrum. Here we describe a family of single-phase solid oxide solutions made from low-cost and non-toxic elements using conventional solid-state methods: [KNbO3]1 - x[BaNi1/2Nb1/2O3 - delta]x (KBNNO). These oxides exhibit both ferroelectricity and a wide variation of direct bandgaps in the range 1.1-3.8 electronvolts. In particular, the x = 0.1 composition is polar at room temperature, has a direct bandgap of 1.39 electronvolts and has a photocurrent density approximately 50 times larger than that of the classic ferroelectric (Pb,La)(Zr,Ti)O3 material. The ability of KBNNO to absorb three to six times more solar energy than the current ferroelectric materials suggests a route to viable ferroelectric semiconductor-based cells for solar energy conversion and other applications. PMID- 24213631 TI - The protein quality control system manages plant defence compound synthesis. AB - Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondary metabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Here we show that, in the legume Medicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD) quality control system to manage the production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membrane-anchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulation is prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues. PMID- 24213633 TI - A chain mechanism for flagellum growth. AB - Bacteria swim by means of long flagella extending from the cell surface. These are assembled from thousands of protein subunits translocated across the cell membrane by an export machinery at the base of each flagellum. Unfolded subunits then transit through a narrow channel at the core of the growing flagellum to the tip, where they crystallize into the nascent structure. As the flagellum lengthens outside the cell, the rate of flagellum growth does not change. The mystery is how subunit transit is maintained at a constant rate without a discernible energy source in the channel of the external flagellum. We present evidence for a simple physical mechanism for flagellum growth that harnesses the entropic force of the unfolded subunits themselves. We show that a subunit docked at the export machinery can be captured by a free subunit through head-to-tail linkage of juxtaposed amino (N)- and carboxy (C)-terminal helices. We propose that sequential rounds of linkage would generate a multisubunit chain that pulls successive subunits into and through the channel to the flagellum tip, and by isolating filaments growing on bacterial cells we reveal the predicted chain of head-to-tail linked subunits in the transit channel of flagella. Thermodynamic analysis confirms that links in the subunit chain can withstand the pulling force generated by rounds of subunit crystallization at the flagellum tip, and polymer theory predicts that as the N terminus of each unfolded subunit crystallizes, the entropic force at the subunit C terminus would increase, rapidly overcoming the threshold required to pull the next subunit from the export machinery. This pulling force would adjust automatically over the increasing length of the growing flagellum, maintaining a constant rate of subunit delivery to the tip. PMID- 24213635 TI - Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway. AB - Obesity has been associated with an increased risk of postmenopausal breast cancer, which may be due to the expression of leptin. The aim of this study was to determine the role of leptin in the growth of breast cancer cells in nude mice, the proliferation and migration of MCF-7 human breast cancer cells and its downstream signaling pathway. The xenograft mouse model was elicited by injecting MCF-7 human breast cancer cells into the left back axilla and the tumor size was measured every other day. Leptin injected subcutaneously around the tumor site led to an increase in the size and weight of the tumor, whereas the leptin antagonist (LA) significantly inhibited the size and weight of the tumor. Leptin promoted the proliferation and migration of MCF-7 cells and LA inhibited it. The effects of leptin on increasing the size and weight of the tumor in the nude mice and the proliferation and migration of MCF-7 human breast cancer cells were eradicated by pretreatment with LA, the extracellular-signal regulated kinase (ERK) inhibitor PD98059. In the xenograft mouse model the leptin level was increased and leptin increased the phosphorylation of ERK in the MCF-7 cells, whereas LA significantly reduced the phosphorylation of ERK. These results indicated that leptin promotes the growth of breast cancer in the nude mice and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway. PMID- 24213634 TI - Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. AB - In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination. Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements. It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space. However, the dynamic nature of chromatin connectivity has not been characterized at the genome wide level. Here, through a chromatin interaction analysis with paired-end tagging approach using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II, we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells, neural stem cells and neurosphere stem/progenitor cells. Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer-promoter associations and delineate cell type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter-enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orchestrating development. PMID- 24213636 TI - Structural aspects of calcium-release activated calcium channel function. AB - Store-operated calcium (Ca(2+)) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca(2+) levels by signaling Ca(2+) release activated Ca(2+) channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca(2+) elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca(2+) sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca(2+) sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID- 24213632 TI - Dysfunctional nitric oxide signalling increases risk of myocardial infarction. AB - Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the alpha1 subunit of soluble guanylyl cyclase (alpha1 sGC), and CCT7 encodes CCTeta, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce alpha1-sGC as well as beta1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in alpha1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction. PMID- 24213637 TI - Study of seasonal variations and health risk assessment of heavy metals in Cyprinus carpio from Rawal Lake, Pakistan. AB - This study was carried out to find out the comparative distribution of heavy metals (Fe, Cu, Mn, Zn, Co, Cr, Cd and Pb) in various tissues (muscles, gills, liver, stomach and intestine) of Cyprinus carpio from Rawal Lake, Pakistan, during summer and winter. Relatively higher concentrations of Cd, Co, Cr, Cu, Fe and Zn were found in the stomach samples, while the highest Pb and Zn levels were noted in muscle and intestine samples, respectively. Correlation study exhibited diverse relationships among the metals in various tissues. Generally, the metal concentrations found during the summer were comparatively higher than the winter. Potential non-carcinogenic and carcinogenic health risks related to the metals in C. carpio were evaluated using the US Environmental Protection Agency approved cancer risk assessment guidelines. The calculated daily and weekly intakes of Pb, Cd, Cr and Co through the fish consumption were significantly higher than the permissible limits. In relation to the non-carcinogenic risks to human, Pb, Cd, Cr, Co and Zn levels were higher than the safe limits; however, carcinogenic risks related to Cr (3.9 * 10(-3) during summer and 1.1 * 10(-3) during winter) and Pb (2.6 * 10(-4) during summer and 1.5 * 10(-4) during winter) clearly exceeded the safe limit (1 * 10(-6)). Consequently, the consumption of C. carpio from Rawal Lake on regular basis was considered unsafe. PMID- 24213638 TI - Distribution and bioaccumulation of organochlorine pesticides (OCPs) in food web of Nansi Lake, China. AB - The concentration of 12 organochlorine pesticides (OCPs) were measured in water, sediment, aquatic plant, and animal (shrimp and fish) of Nansi Lake by gas chromatography equipped with an electron capture detector. The total OCPs concentrations were 65.31-100.31 ng L(-1) in water, 2.9-6.91 ng g(-1) dry weight (dw) in sediments, 1.29-6.42 ng g(-1) dw in aquatic plants and 7.57-17.22 ng g( 1) dw in animals. The OCPs composition profiles showed that heptachlor compounds was also the predominant OCPs contaminants in addition to hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs) in Nansi Lake. According to the source of HCHs and DDTs in sediment samples, there was no new input and the HCHs pollution mainly came from the use of Lindane in Nansi Lake. Bioaccumulation of OCPs in aquatic biota indicated that DDTs and heptachlor compounds had a strong accumulation, followed by HCHs and drins. The accumulation abilities of fish for OCPs were higher than those of plants and shrimps. The OCPs biota sediment accumulation factor values of Channa argus was the highest in fish samples, followed by Carassius auratus, and Cyprinus caspio. Risk assessment of sediment showed that heptachlor epoxide had a higher occurrence possibility of adverse ecological effects to benthic species. Based on the calculation of acceptable daily intake and hazard ratio, HCHs in fish and shrimps from Nansi Lake had a lifetime cancer risk of greater than one per million. The risk assessment of water, sediment, and fish indicated the water environment of Nansi Lake is at a safe level at present. PMID- 24213639 TI - Water and sediment quality in Qinghai Lake, China: a revisit after half a century. AB - Qinghai Lake, situated on the Qinghai-Tibet plateau, is the largest lake in China. In this study, the water and sediment quality were investigated in Qinghai Lake, three sublakes, and five major tributaries. Both Na(+) and Cl(-) were found to be the major ions present in Qinghai Lake and the three sublakes, while Ca(2+) and HCO(3-) dominated the tributaries. Compared with historical data from the 1960s, the concentrations of NH4(+), NO3(-), and soluble reactive silica have increased considerably, likely caused by increased human activities in the area. Compared to the historical data, chemical oxygen demand has increased and lake water transparency has decreased, likely related to an increase in nutrient levels. Relatively high concentrations of total nitrogen (TN) and total phosphorus (TP) were observed in Qinghai Lake sediments, although P fraction types and low water concentrations of these two indicate low possibility of transfer into the water column. The ratios of C/N suggest that the organic matter in the sediments are primarily from autochthonous sources. TN and total organic carbon in the sediment cores increased slowly up the core while TP and total inorganic carbon have been fairly constant. PMID- 24213640 TI - Opaque closed chambers underestimate methane fluxes of Phragmites australis (Cav.) Trin. ex Steud. AB - Closed chamber measurements for methane emission estimation are often carried out with opaque chambers to avoid heating of the headspace. However, mainly in wetlands, some plants possess an internal convective gas transport which quickly responds to changes in irradiation. These plants have also been found to often channel a large part of the released methane in temperate fens. We compare methane fluxes derived from transparent versus opaque chambers on Carex-, Phragmites-, and Typha-dominated stands of a temperate fen. Transparent chamber fluxes almost doubled opaque chamber fluxes in the convective transporting Phragmites stand. In Typha, a trend of higher fluxes determined with the transparent chambers was detectable, whereas in Carex, transparent and opaque chamber fluxes did not differ significantly. Thus, opaque chambers bias the outcome of methane measurements, depending on dominant vegetation. We recommend the use of transparent chambers when determining emissions of convective plants or extrapolating fluxes to larger scales. PMID- 24213642 TI - Editorial. PMID- 24213643 TI - Health hazards of mining. AB - Mining is inherently dangerous both in terms of accident and ill health. Some of the health hazards are common to mining in general; others are related specifically to the nature of the material being mined, though the miner is sometimes at less risk than those who refine and use the product. The answer to the health problems is knowledge of the hazard and concern for the welfare of others on the part of workers, managers, legislators and administrators. PMID- 24213641 TI - Assembly errors cause false tandem duplicate regions in the chicken (Gallus gallus) genome sequence. AB - The complexity of eukaryote genomes makes assembly errors inevitable in the process of constructing reference genomes. Next-generation sequencing (NGS) could provide an efficient way to validate previously assembled genomes. Here, we exploited NGS data to interrogate the chicken reference genome and identified 35 pairs of nearly identical regions with >99.5 % sequence similarity and a median size of 109 kb. Several lines of evidence, including read depth, the composition of junction sequences, and sequence similarity, suggest that these regions present genome assembly errors and should be excluded from forthcoming genomic studies. PMID- 24213644 TI - Comparison of health patterns in two geochemically contrasted areas of northern Finland. AB - In order to prepare the ground for a discussion of possible causal relationships between health patterns and the geochemistry of an area, health patterns in the form of age-adjusted cancer incidence values and rates of mortality due to (1) cancer of the stomach, colon or rectum, (2) lung cancer and (3) ischaemic heart diseases are compared between the populations of two geochemically contrasted communes of northern Finland (Kemijarvi and Kuusamo). Statistically significant differences (p < 0.001) are encountered in the mortality rates due to ischaemic heart diseases and marked differences in the incidence values of lung cancer, the former being higher in Kuusamo and the latter in Kemijarvi. The higher incidence of lung cancer observed in Kemijarvi is in accordance with previous results reported from the USA, where higher incidences have been observed in areas of granitic bedrock. Regarding the higher mortality rate due to ischaemic heart diseases In Kuusamo, which is geochemically characterised by higher potassium (p < 0.002) and calcium (p < 0.004) and lower Zn, V, Ti, and Fe (p > 0.002) in the soil (actually, in the fine till fraction), no easily demonstrable cause- and effect relationship can be established. PMID- 24213645 TI - The trace element composition of stream- and melt-waters at times of the spring thaw in the Scottish Highlands. AB - Fresh snow and streamwater samples were collected on a daily basis throughout the winter and spring periods of 1984 and 1985 at a remote, upland catchment located within the Cairngorm Mountains, Scotland. Laboratory based partial-melt experiments undertaken on the snow samples demonstrated that both fractionation and preferential elution of trace-elements occur during melting, with the concentrations being 1.3 to 5.4 times greater than in the first 10 percent meltwater fractions than in the bulk snow (Abrahamset al., in press). At the onset of snowpack melting, the ions may be mobilised and redistributed within the snow profile, concentrating at depths from where they may be quickly removed during the early spring run-offf. The raised major- (Ca, Mg, Na, Cl, NO3 and SO4) and trace-element (Al, Cd, Cu, Fe, Mn and Pb) concentrations recorded in the streamwaters during the "acid-flush" episodes at the time of the first major periods of snow-melt, reflect both the meltwater composition and the influence of the catchment soils (Abrahamset al., submitted for publication). Differences in streamwater chemistry during the two periods of snow-melt which were studies can probably be related to the fact that snow-melt occurs under a variety of circumstances with significant variations in the sequence of precipitation, melt events, temperature and snowcover occurring from year to year, even in the same catchment. The high concentrations of Al (up to 330 MUg L(-1)) in the sireamwaters at the time of snow-melt, probably reflect leaching of this element from the soil. These elevated concentrations, in combination with other streamwater parameters, may prove toxic to aquatic life-forms at this time of year. PMID- 24213646 TI - Inorganic element uptake by barley from soil supplemented with flue-gas desulphurisation waste and fly-ash. PMID- 24213647 TI - Reactions between aqueous zinc, aluminium and iron with increasing solutionpH. AB - Solutions of zinc, aluminium and/or iron, as chlorides in NaCl of ionic strength 0.13 mol/l atpH 3, were mixed to give initial concentrations of 0-5, 5-50 and 10 100 MUg/ml, respectively. Sodium hydroxide was then added to increase thepH in a range up to 7. Turbidity was measured and equilibrium concentrations were determined after filtration (< 0.1 MUm). Decrease inpH on mixing suggested an immediate reaction, with the release of protons. At allpH values Zn concentration decreased with increasing initiai concentrations of Fe and Al. Adsorption and/or nucleation of Zn with Fe and Al was highlypH dependent and increased markediy with increasingpH. The particle size of the products increased with increasingpH and initial concentration of the elements. Increasing Al concentration decreased the size of Fe nucleates at a given Fe concentration. The results suggest that co precipitation may be involved as well as adsorption. This has important consequences for the availability of Zn to plants, especially in Zn-deficient soils, and is of relevance to the products of mixing acid drainage waters with streams and lakes. PMID- 24213648 TI - The interpretation of noisy data from archaeological field survey: Phosphate analysis. AB - High soil phosphate concentrations are commonly related to intense past human activity although full understanding of this relationship requires further research. At present, practical constraints in the field, the need for extensive sampling and for rapid results, leads to the archaeologist frequently using crude but portable techniques of chemical analysis. The problems associated with the collection and interpretation of archaeological soil phosphate data are discussed. The use of Bayesian change-point analysis is proposed as a suitable statistical aid to the interpretation of such data. PMID- 24213649 TI - Fluorine in the UK environment. AB - Relatively low concentrations of fluorine in drinking water (<= 1 mg F/l) have been shown to significantly reduce the degree of dental caries in children and fluorine would also appear to have a beneficial effect on bone formation in both humans and farm animals. However, it is apparent that elevated levels of fluorine in the diet have sometimes resulted in problems of increased dental caries and of the development of bone deformities. Much of the fluorine in rocks and soils occurs in apatite and hydroxysilicate minerals, fluorite being the only relatively common rock forming mineral containing fluorine as an essential constituent.Little systematic data are available on fluorine concentrations in soils, plants and natural waters in the UK. General background soil concentrations lie in the range 200 - 400 mg F/kg. For waters the average fluorine content is low, <0.1 mg F/l.In the British Isles there are several areas where there are enhanced levels of fluorine. In the northern Pennines, Derbyshire, northeast Wales and Cornwall, fluorite occurs as a significant component of mineralisation and much fluorine has been added to the environment from mining waste dumps. Soils in northeast Wales contain up to 3,650 mg F/kg and in the northern Pennines up to 20,000 mg F/kg. Waters contain up to 2.3 mg F/l. In southwest England, the granites are generally fluorine-rich with the fluorite granites of the St Austell pluton containing as much as 1 percent fluorine. These rocks are frequently kaolinised and intensively worked as a source of china clay. Soils in the vicinity of the waste tips contain up to 3,300 mg F/kg and grasses up to 2,950 mg F/kg. Surface waters in the St Austell area contain up to 1.25 mg F/l.Atmospheric fluorine pollution around brickworks in the Peterborough and Bedford areas has resulted in fluorosis in farm animals. Other sources of atmospheric fluorine pollution are aluminium smelters, steelworks and fossil fuel burning. PMID- 24213650 TI - Trace element analysis of soil samples from a stratified archaeological site. AB - Thirty-eight soil samples from a sondage excavated through a 6- metre stratified tell (Gomoiava, in central Yugoslavia) have been analysed for nine biophile elements: Mg, Sr, Zn, Cu, Ni, Mn, Cr, Pb and B. The site was occupied from 7000 BC to 500 AD (calendar years). The results have been collated with earlier estimates of P and Ca, made on a larger series of samples from the same site. The results are discussed in terms of useful information, to supplement that given by phosphate analysis, about stratification and the relationship of the settlement to its environment.It is concluded that leaching probably distorts the results for Ca and Mg. The results for Mn may help to distinguish phosphate accumulation due to man from that due to farm livestock. There is significant accumulation of Sr and B, both of which have potential value, although some of the analytical results for the latter are suspect. The results for Zn, Cu and Ni are highly correlated, with sharp peaks which couid provide precise information about individual strata when more experience of interpretation has been gained. Only Cr and Pb appear to provide little useful information at this site. PMID- 24213651 TI - Accumulation of metals in the tissues of occupationally exposed workers. AB - Neutron activation analysis has been used to assess the accumulation of metals in lung and other tissue takenpost mortem from occupationally exposed workers. Two groups together with controls have been examined. Twenty-one workers from northern Sweden, previously employed in metal refining, show concentrations of several metals above that in the controls. Increased metal concentrations in lung tissues are also observed in groups of coal miners from the United Kingdom. These results are discussed in relation to the amounts of industrial pollutants taken into lung and their retention periods as a means of estimating the occupational exposure dose. PMID- 24213652 TI - A spectroscopic study on the coordination and solution structures of the interaction systems between biperoxidovanadate complexes and the pyrazolylpyridine-like ligands. AB - In order to understand the substitution effects of pyrazolylpyridine (pzpy) on the coordination reaction equilibria, the interactions between a series of pzpy like ligands and biperoxidovanadate ([OV(O2)2(D2O)](-)/[OV(O2)2(HOD)](-), abbrv. bpV) have been explored using a combination of multinuclear ((1)H, (13)C, and (51)V) magnetic resonance, heteronuclear single quantum coherence (HSQC), and variable temperature NMR in a 0.15 mol L(-1) NaCl D2O solution that mimics the physiological conditions. Both the direct NMR data and the equilibrium constants are reported for the first time. A series of new hepta-coordinated peroxidovanadate species [OV(O2)2L](-) (L = pzpy-like chelating ligands) are formed due to several competitive coordination interactions. According to the equilibrium constants for products between bpV and the pzpy-like ligands, the relative affinity of the ligands is found to be pzpy > 2-Ester-pzpy ~ 2-Me-pzpy ~ 2-Amide-pzpy > 2-Et-pzpy. In the interaction system between bpV and pzpy, a pair of isomers (Isomers A and B) are observed in aqueous solution, which are attributed to different types of coordination modes between the metal center and the ligands, while the crystal structure of NH4[OV(O2)2(pzpy)].6H2O (CCDC 898554) has the same coordination structure as Isomer A (the main product for pzpy). For the N-substituted ligands, however, Isomer A or B type complexes can also be observed in solution but the molar ratios of the isomer are reversed (i.e., Isomer B type is the main product). These results demonstrate that when the N atom in the pyrazole ring has a substitution group, hydrogen bonding (from the H atom in the pyrazole ring), the steric effect (from alkyl) and the solvation effect (from the ester or amide group) can jointly affect the coordination reaction equilibrium. PMID- 24213653 TI - Physicochemical, antimicrobial and antioxidant properties of chitosan films incorporated with carvacrol. AB - Chitosan films (CF) with carvacrol (CAR) [0.5%, 1.0% and 1.5% v/v] were prepared by the emulsion method. The retained CAR, water solubility, water vapor permeability (WVP), optical, mechanical properties, antibacterial and antioxidant capacity of films were analyzed. The results indicate that the retention of CAR in the CF was ~50%. The incorporation of CAR to CF decreased the water solubility, the WVP, the yellowing and transparency and the tensile strength, but increased the stiffness. Microcapsules with diameters of 2 to 7 um were found on the surface CF-CAR. The CF-CAR with highest CAR concentrations showed antibacterial activity against S. typhimurium and E. coli O157:H7. The CF-CAR had higher antioxidant capacity and an increased protective effect against oxidation of erythrocytes in different grades. These results suggest potential applications of CF-CAR as active packaging to preserve food products. PMID- 24213654 TI - Selective oxidation reactions of natural compounds with hydrogen peroxide mediated by methyltrioxorhenium. AB - We have investigated the oxidative behaviour of natural compounds such as methyl abietate (1), farnesyl acetate (2), alpha-ionone (3), beta-ionone (4), methyl linolelaidate (5), methyl linolenate (6) and bergamottin (7) with the oxidant system methyltrioxo-rhenium/ H2O2/pyridine. The reactions, performed in CH2Cl2/H2O at 25 degrees C, have shown good regio- and stereoselectivity. The oxidation products were isolated by HPLC or silica gel chromatography and characterized by MS(EI), 1H-, 13C-NMR, APT, gCOSY, HSQC, TOCSY and NOESY measurements. The selectivity seems to be controlled by the nucleophilicity of double bonds and by stereoelectronic and steric effects. PMID- 24213655 TI - The Janus face of PAMAM dendrimers used to potentially cure nonenzymatic modifications of biomacromolecules in metabolic disorders-a critical review of the pros and cons. AB - Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer's disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia. PMID- 24213656 TI - Baeyer-Villiger oxidation of some C(19) steroids by Penicillium lanosocoeruleum. AB - The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum-a fungal species not used in biotransformations so far-were described. All the substrates were converted in high yield (70%-99%) into D ring delta-lactones. The oxidation of 1 produced 3alpha-hydroxy-17a-oxa-D-homo-5alpha-androstan-17-one (5). The oxidation of 2 led to 3beta-hydroxy-17a-oxa-D-homo-5alpha-androstan-17-one (6). The biotransformation of 3 resulted in the formation of 3alpha-hydroxy-17a-oxa-D homo-5alpha-androstan-17-one (5) and 17a-oxa-D-homo-5alpha-androstan-3,17-dione (7). An analysis of the transformation progress of the studied substrates as a function of time indicates that the Baeyer-Villiger monooxygenase of this fungus does not accept the 3beta-hydroxy-5-ene functionality of steroids. In this microorganism steroidal 3beta-hydroxy-dehydrogenase (3beta-HSD) was active, and as a result DHEA (4) was transformed exclusively to testololactone (8). Apart from the observed oxidative transformations, a reductive pathway was revealed with the C-3 ketone being reduced to a C-3alpha-alcohol. It is demonstrated for the first time that the reduction of the 3-keto group of the steroid nucleus can occur in the presence of a ring-D lactone functionality. PMID- 24213657 TI - Culture conditions for induction of green plants from barley microspores by anther culture methods. AB - With barley a large variation in frequency of plant formation from microspores of spikes from the same plant has been observed. The highest frequency of plant formation was obtained when culturing anthers in the dark on a high Ficoll medium containing 2,4-D and kinetin to induce proembryo (or callus) formation. Subsequently the proembryos or calli were cultured in dim light on a high Ficoll high sugar medium containing IBA and kinetin. Finally the embryos were transferred to a starch agar medium. A maximum of 13 green plants were obtained from microspores of a single anther.The ratios of green to albino microspore derived plants varied from 9?1 to 1?9 depending on culture conditions. Under anaerobic conditions, lactic acid and other organic acids may have damaged the organelles in the cells resulting in the formation of albino plants. Thus, direct embryogenesis by using a well-buffered, high Ficoll-high sugar medium and proper aeration are essential for obtaining high frequency of green plants from microspores. PMID- 24213658 TI - Electroporated protoplasts express seed specific gene promoters. AB - The soybean 7S seed storage protein, beta-conglycinin, is comprised of three major subunits, alpha', alpha, and beta. Chimeric genes having beta-conglycinin alpha' and beta subunit promoters and the beta-glucuronidase gene coding sequence were constructed and electroporated into protoplasts prepared from three cultured cell lines and from tobacco mesophyll cells. The beta-conglycinin promoters were active in all protoplasts examined, and their activities were 10-60% of that of the cauliflower mosaic virus 35S promoter. In electroporated protoplasts isolated from tobacco suspension cultures the time course of expression and the pattern of cell cycle dependency of the beta-conglycinin promoters were similar to those of the 35S promoter. The responses to exogenously added L-methionine and abscisic acid, which are known to have differential effects on the expression of beta conglycinin promoters in cultured soybean cotyledons, were essentially the same among the promoters used. The results indicate that beta-conglycinin promoters are expressed in electroporated protoplasts, but their regulation is relaxed. PMID- 24213659 TI - Effect of Alternaria solani culture filtrate on adventitious shoot regeneration in potato. AB - The effect of Alternaria solani culture filtrate on adventitious shoot regeneration from tuber discs was evaluated using five potato cultivars, which were selected based on their field reaction to Alternaria solani and which represented a range of disease reactions. The culture filtrate stimulated regeneration, a response that could prove to be very useful in the wider utilization of transformation and in vitro selection technology. PMID- 24213660 TI - Plant regeneration from protoplasts isolated from long-term cell cultures of wheat (Triticum aestivum L.). AB - A friable and fast-growing type of callus was isolated from a long term shoot competent cell culture of wheat. The suspension cultures established from this callus consisted of small, densely cytoplasmic cells which divided more rapidly but with a lower plant regeneration frequency than the original culture. A high yield of protoplasts was released from suspension cells (2 to 3*10(7) protoplasts per ml packed cell volume) when treated with enzyme mixtures. The isolated protoplasts divided at a relatively high frequency (20% to 50%) in both liquid and agarose-solidified KM8p medium. Up to 0.21% of the dividing protoplasts continued to divide and form micro-calli. Sixty-eight plants were regenerated from micro-calli, and among the 30 plants which were transplanted to the greenhouse, 3 have survived. PMID- 24213661 TI - Transient expression of beta-glucuronidase in different cellular compartments following biolistic delivery of foreign DNA into wheat leaves and calli. AB - Transient expression of beta-glucuronidase (GUS) in different cellular compartments following biolistic delivery of chloroplast or nuclear expression vectors into wheat leaves or calli, derived from anther culture or immature embryos, is reported here. When pB1121, the nuclear GUS vector, was used to bombard wheat cells, the beta-glucuronidase product, an insoluble indigo dye, was observed evenly throughout the cytosol. But, when the chloroplast expression vector pHD203-GUS was used for bombardments, the indigo dye (GUS product) was subcellularly localized within the chloroplasts of wheat cells. The observation of GUS expression in albino plastids, when anther culture derived albino leaves were bombarded with the chloroplast expression vector pHD203-GUS, suggests the presence of a functional protein synthetic machinery in these organelles. GUS expression was also observed in regenerable calli derived from wheat immature embryos bombarded with pHD203-GUS. Leaves or calli bombarded with pUC19, as negative controls, did not show any GUS expression. These results constitute the first demonstration of foreign gene expression in chloroplasts of a monocot and that a dicot chloroplast promoter functions in a monocot chloroplast. PMID- 24213662 TI - Somatic embryogenesis and plant regeneration of squash Cucurbita pepo L cv. YC 60. AB - Plant regeneration from tissue cultures of summer squash, Cucurbita pepo L., cv. YC60, has been observed. Somatic embryos organized from shoot apex derived callus cultured on Murashige and Skoog (MS) medium supplemented with 1.2 mg/l 2,4,5 trichlorophenoxyacetic acid, 0.8 mg/l benzylaminopurine, and 0.1 mg/l kinetin. Embryos developed into plantlets by transfer of immature somatic embryos to MS medium with 0.05 mg/l NAA and 0.05 mg/l kinetin. Regenerated plants appeared morphologically normal and set fruits with seeds which could germinate normally. PMID- 24213663 TI - Plant development in long-term embryogenic callus lines of Cucurbita pepo. AB - Embryogenic callus derived from pumpkin hypocotyl segments was induced and maintained for 15 years on MS medium supplemented with the auxins IBA (4.9 MUM), 2, 4-D (4.5 MUM) or IAA (5.7 MUM). On induction media continued embryo maturation and development of adult plants typically failed. Therefore, small embryogenic clumps and individually isolated embryos were subcultured two to four times on one of the conversion media: MS supplemented with 1.5% sucrose and (a) no hormone, (b) 2.9 MUM IAA, (c) 5.7 MUM IAA, (d) 11.4 MUM IAA, (e) 12 MUM IEt, (f) 3.8 MUM ABA or (g) 2% activated charcoal. The cell line and the kind of auxin used in the induction and maintenance medium, both had a marked influence on the development of plantlets. The best result was achieved with a line that has been induced and maintained for 15 years on MS with IBA. In the IBA line, out of 100 embryos, 77 developed into plantlets on MS medium supplemented with 11.4 MUM IAA. PMID- 24213664 TI - Growth and thiophene accumulation by hairy root cultures of Tagetes patula in media of varying initial pH. AB - Hairy roots of Tagetes patula were grown for 24 days in modified Murashige and Skoog's liquid medium at different initial pH levels of 4.0, 5.0, 5.7, 6.0 and 7.0. Irrespective of the initial pH, after 12 days, the pH of the culture medium was approximately 4.5. However the final pH, after 24 days of growth, did depend weakly on the initial pH of the medium. The biomass yield was lowest at an initial pH of 4.0, possibly due to lower utilization of ammonium at this pH. Similar patterns of thiophene accumulation was observed at all pH levels tested. Maximum thiophene accumulation occurred in root cultures which were 12-16 days old. PMID- 24213665 TI - Barley anther culture: The effect of position on pollen development in vivo and in vitro. AB - Locule structure and organization were studied in vivo and in vitro to determine whether the disposition of pollen within barley anthers affected the response of pollen in culture. Following release from the meiotic tetrads, juvenile barley microspores become peripherally organized around the locule, with the single pollen pore oriented towards the tapetum. Scanning electron micrographs of transverse sections from freeze fractured anthers showed that some microspores failed to locate the tapetal surface and occupied a position in the centre of the locule where they continued to develop as small, abnormal pollen grains (dimorphic pollen). Previous evidence has suggested that in some species dimorphic pollen could be the source of embryonic pollen in vitro. Cultured anthers frequently dehisced to reveal a mass of dividing pollen grains, however those anthers that remained intact retained the original locule structure and could be freeze fractured permitting examination of the developing pollen in situ. This showed that pollen embryogenesis was not restricted to dimorphic pollen, and that any grain could become Embryogenic irrespective of position. PMID- 24213666 TI - Studies on plant regeneration from protoplasts in the genus Helianthus. AB - Protoplasts were produced from 7-day-old hypocotyls of two cultivated sunflower genotypes and three wild sunflowers. When included in agarose droplets and cultured in TL medium supplemented with 0.1 mg/l 2,4-dichlorophenoxyacetic acid, the protoplasts gave rise to loose colonies and to "embryoids". After two months the small calli emerging from the agarose were transferred to a regeneration medium on which they grew and began to differentiate. A second transfer to the same medium 40 days later induced shoot formation on one callus of H. petiolaris. Several shoots were successfully rooted and transferred to soil where they flowered. This is the first documented report, in the genus Helianthus. of regeneration from protoplasts to fully soil-adapted plants. PMID- 24213667 TI - Interspecific hybridization between Brassica juncea and B. spinescens through protoplast fusion. AB - Hypocotyl derived protoplasts of B. juncea cv. RLM-198 were fused with mesophyll protoplasts of B. spinescens using polyethylene glycol to produce interspecific hybrids. Fusion products could be microscopically identified by characteristics of the protoplasts of both parents in the hybrid cells; they are colourless and vacuolated like the hypocotyl protoplasts and possess chloroplasts of the mesophyll protoplasts. The heterokaryotic fusion frequency was around 5%. However, the frequency of calli regenerating hybrid shoots was more than 10% of the regenerating calli. Putative somatic hybrids had morphological features characteristic of both the parents. Twelve plants analysed cytologically, possessed 52 chromosomes (26II) at meiosis representing the complete genomes of B. juncea (18II) and B. spinescens (8II). For esterase isozymes, the hybrids had bands of Doth the parents. Hybrid nature of some of the plants was confirmed by their close resemblance to B. juncea, chromosome number and isozyme bands of B. spinescens as in Rsp-19. Somatic hybrids had rudimentary, non-dehiscent anthers and completely sterile pollen. However, on back crossing with B. juncea, 10 out of 12 plants produced seeds and about 100 plants were realized. PMID- 24213668 TI - Plant regeneration from protoplasts of long-term callus cultures of Actinidia deliciosa var. deliciosa cv. Hayword (Kiwifruit). AB - Plant regeneration of Actinidia deliciosa var. deliciosa cv. Hayword was obtained from protoplasts isolated from petiole derived long-term callus cultures. Protoplasts were cultured in liquid medium over agarose gelled medium. Regenerated green callus, plated on solid medium, could develop shoots that rooted spontaneously in hormone-less medium. The plants obtained are growing fast in soil and present a normal phenotype. PMID- 24213669 TI - Roots induced on cucumber cotyledons by the agropine Ri plasmid TR-DNA exhibit the transformed phenotype. AB - Cucumber explants were transformed by Agrabacterium strains carrying Ri plasmids with functional TL and TR-DNAs, and by strains whose pRi had an intact TR-DNA but a disarmed TL-DNA lacking open reading frames (ORFs) 3 to 9, 10 (rol A), 11 (rol B), 12 (rol C), 13, 14, 15 (rol D), 16 and 17. Roots induced by all strains exhibited extensive root hair formation under axenic conditions, synthesised opines, and contained TR-specific DNA. These results confirm that the TR-DNA of an agropine Ri plasmid is able to elicit the transformed root phenotype in this plant. PMID- 24213670 TI - Agrobacterium induced gall formation in lipoxygenase mutant isolines of soybeans. AB - Agrobacterium-mediated transformation frequency is very low with cells from some species such as soybeans. Studies were conducted to investigate the Agrobacterium mediated transformation frequency in near-isogenic lipoxygenase mutant lines of soybeans, since the nigh level of lipoxygenase activity in soybean embryos might be expected to affect interactions with Agrobacterium. The mutant line lacking lipoxygenase 3 showed significantly greater frequency of Agrobacterium-induced transformation than the other soybean lines. Stages of soybean embryo development which showed maximum differences in lipoxygenase 3 activity between mutant and wild-type, also showed maximum differences in transformation frequency. The increased transformation frequency with the absence of lipoxygenase 3 was only seen when both lipoxygenase 1 and 2 were present. PMID- 24213671 TI - Altered default mode and affective network connectivity in stroke patients with and without dysphagia. AB - OBJECTIVE: Neuroimaging studies in stroke patients provide substantial evidence for the involvement of widespread cortical and subcortical regions in the control of swallowing. Although the affective network and the default mode network are functionally related to "autonomic" and "volitional" swallowing, little is known about their functional changes in dysphagic stroke patients. METHODS: Unbiased seeds functional connectivity analysis was used to study the connectivity patterns of these resting-state networks. Resting-state functional magnetic resonance imaging was performed in stroke patients with (n = 12) and without dysphagia (n = 12). RESULTS: Compared with healthy controls, stroke patients with and without dysphagia had decreased functional connectivity in the default mode network and the affective network. Moreover, stroke patients with dysphagia also had decreased functional connectivity in both the default mode network and the affective network relative to patients without dysphagia. CONCLUSION: The difference in the extent of impairment in the default mode network and affective network of stroke patients with and without dysphagia may lead to improved understanding of the neuropathophysiological mechanism and rehabilitation of dysphagia. PMID- 24213673 TI - Cytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells. AB - Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in the nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue are still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-alpha (TNF-alpha)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref-1 was mainly observed in the nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-alpha. Cytoplasmic APE1/Ref 1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of an N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-alpha-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-alpha-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with its anti-inflammatory activity in endothelial cells. PMID- 24213674 TI - Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity. AB - To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of Major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and alpha3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells. PMID- 24213675 TI - Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels. AB - The hyaloid vessel is a transient vascular network that nourishes the lens and the primary vitreous in the early developmental periods. In hyaloid vessels devoid of the support of astrocytes, we demonstrate that tight junction proteins, zonula occludens-1 and occludin, are regularly expressed at the junction of endothelial cells. To figure out the factor influencing the formation of tight junctions in hyaloid vessels, we further progress to investigate the interactions between endothelial cells and pericytes, two representative constituent cells in hyaloid vessels. Interestingly, endothelial cells interact with pericytes in the early postnatal periods and the interaction between two cell types provokes the up-regulation of transforming growth factor beta1. Further in vitro experiments demonstrate that transforming growth factor beta1 induces the activation of Smad2 and Smad3 and the formation of tight junction proteins. Taken together, in hyaloid vessels, pericytes seem to regulate the formation of tight junctions by the interaction with endothelial cells even without the support of astrocytes. Additionally, we suggest that the hyaloid vessel is a valuable system that can be utilized for the investigation of cell-cell interaction in the formation of tight junctions in developing vasculatures. PMID- 24213676 TI - Regulation of SIRT1 by microRNAs. AB - Sirtuin 1 (SIRT1) is an NAD(+)-dependent deacetylase that connects cellular energy levels to homeostatic responses by deacetylating and modulating the activities of many transcriptional regulators. Discovered as a longevity protein in yeast, the mammalian SIRT1 has been intensively studied because of its great potential as a therapeutic target to benefit human health by preventing and improving many age-related diseases. There has been, therefore, substantial interest in developing agents that upregulate SIRT1 expression and activity. SIRT1 is regulated at multiple levels, including post-transcriptionally by microRNAs (miRs), powerful regulators of diverse biological pathways. Here we discuss how expression and activity of SIRT1 and other sirtuins are inhibited by miRs and further discuss the therapeutic potential of targeting miRs for age related diseases that involve SIRT1 dysfunction, focusing on obesityrelated diseases. PMID- 24213677 TI - Crosstalk between autophagy and inflammasomes. AB - A variety of cellular stresses activate the autophagy pathway, which is fundamentally important in protection against injurious stimuli. Defects in the autophagy process are associated with a variety of human diseases, including inflammatory and metabolic diseases. The inflammasomes are emerging as key signaling platforms directing the maturation and secretion of interleukin-1 family cytokines in response to pathogenic and sterile stimuli. Recent studies have identified the critical role of inflammasome activation in host defense and inflammation. Delineation of the relationship between autophagy and inflammasome activation is now being greatly facilitated by the use of mice models of autophagy gene deficiency and clinical studies. We surveyed the recent research regarding the contribution of autophagy to the control of inflammation, in particular the association between autophagy and inflammasomes. Understanding the mechanisms by which autophagy balances inflammation might facilitate the development of autophagy-based therapeutic modalities for infectious and inflammatory diseases. PMID- 24213678 TI - Real-time monitoring of ozone in air using substrate-integrated hollow waveguide mid-infrared sensors. AB - Ozone is a strong oxidant that is globally used as disinfection agent for many purposes including indoor building air cleaning, during food preparation procedures, and for control and killing of bacteria such as E. coli and S. aureus. However, it has been shown that effective ozone concentrations for controlling e.g., microbial growth need to be higher than 5 ppm, thereby exceeding the recommended U.S. EPA threshold more than 10 times. Consequently, real-time monitoring of such ozone concentration levels is essential. Here, we describe the first online gas sensing system combining a compact Fourier transform infrared (FTIR) spectrometer with a new generation of gas cells, a so called substrate-integrated hollow waveguide (iHWG). The sensor was calibrated using an UV lamp for the controlled generation of ozone in synthetic air. A calibration function was established in the concentration range of 0.3-5.4 mmol m 3 enabling a calculated limit of detection (LOD) at 0.14 mmol m-3 (3.5 ppm) of ozone. Given the adaptability of the developed IR sensing device toward a series of relevant air pollutants, and considering the potential for miniaturization e.g., in combination with tunable quantum cascade lasers in lieu of the FTIR spectrometer, a wide range of sensing and monitoring applications of beyond ozone analysis are anticipated. PMID- 24213679 TI - Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? AB - Regulatory T cells (Treg) play a key role in maintaining the balance of immune responses in human health and in disease. Treg come in many flavors and can utilize a variety of mechanisms to modulate immune responses. In cancer, inducible (i) or adaptive Treg expand, accumulate in tissues and the peripheral blood of patients, and represent a functionally prominent component of CD4+ T lymphocytes. Phenotypically and functionally, iTreg are distinct from natural (n) Treg. A subset of iTreg expressing ectonucleotidases, CD39 and CD73, is able to hydrolyze ATP to 5'-AMP and adenosine (ADO) and thus mediate suppression of those immune cells which express ADO receptors. iTeg can also produce prostaglandin E2 (PGE2). These iTreg, expanding in response to tumor antigens and cytokines such as TGF-beta or IL-10, are presumably responsible for the suppression of anti tumor immune responses and for successful tumor escape. On the other hand, in cancers associated with prominent inflammatory infiltrates, e.g., colorectal carcinoma or certain types of breast cancer, iTreg down-regulate excessive inflammation by producing ADO and/or PGE2 and protect the host from tissue injury and tumor development. Thus, iTreg utilizing the same adenosine pathway play a key but dual role in cancer, and their plasticity is controlled and driven by the microenvironment. Thus, monitoring for the frequency and functions of iTreg rather than nTreg is important in cancer. In addition, elimination of iTreg by various available strategies prior to immunotherapies may not be beneficial in all cases and needs to be undertaken with caution. PMID- 24213680 TI - Estimating the sex-specific effects of genes on facial attractiveness and sexual dimorphism. AB - Human facial attractiveness and facial sexual dimorphism (masculinity-femininity) are important facets of mate choice and are hypothesized to honestly advertise genetic quality. However, it is unclear whether genes influencing facial attractiveness and masculinity-femininity have similar, opposing, or independent effects across sex, and the heritability of these phenotypes is poorly characterized. To investigate these issues, we assessed facial attractiveness and facial masculinity-femininity in the largest genetically informative sample (n = 1,580 same- and opposite-sex twin pairs and siblings) to assess these questions to date. The heritability was ~0.50-0.70 for attractiveness and ~0.40-0.50 for facial masculinity-femininity, indicating that, despite ostensible selection on genes influencing these traits, substantial genetic variation persists in both. Importantly, we found evidence for intralocus sexual conflict, whereby alleles that increase masculinity in males have the same effect in females. Additionally, genetic influences on attractiveness were shared across the sexes, suggesting that attractive fathers tend to have attractive daughters and attractive mothers tend to have attractive sons. PMID- 24213681 TI - High-throughput tandem-microwell assay identifies inhibitors of the hydrogen sulfide signaling pathway. AB - We report a high-throughput assay for H2S-producing enzymes, which is based on a newly designed tandem-well plate. Screening of 21,599 agents identified several potent inhibitors of cystathionine beta-synthase and cystathionine gamma-lyase, the two key enzymes generating H2S in mammals, with IC50 values in the low two digit micromolar range. PMID- 24213682 TI - Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review. AB - Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease. PMID- 24213683 TI - Anxiety and low life satisfaction associate with high caregiver strain early after stroke. AB - OBJECTIVE: Caregivers play an important role in the well-being of stroke patients, and are known to experience considerable strain 3 months or more after patient discharge. The aim of this study was to determine the prevalence and determinants of caregiver strain early after discharge. METHODS: Six weeks after discharge from the hospital or rehabilitation setting stroke-surviving patients and their caregivers were seen by a specialized nurse. Several screening lists, including the Caregiver Strain Index (CSI), were completed. Step-wise logistic regression was used to analyse which determinants independently contribute to caregiver strain. RESULTS: A total of 284 stroke-surviving patients were included in the study. Of the 179 caregivers who completed the CSI, 23 (12.8%) experienced considerable strain. A higher level of anxiety symptoms and lower life satisfaction in patients are independently associated with higher caregiver strain (p = 0.000007 and p = 0.0031, respectively). CONCLUSION: High strain is experienced by 12.8% of caregivers shortly after discharge of a stroke-surviving patient. More anxiety symptoms and lower life satisfaction in patients are independently associated with a higher level of strain in caregivers. Treating patient anxiety at an early stage might therefore lead to a decrease in long-term caregiver strain. PMID- 24213684 TI - Kinematics of the knee after unicompartmental arthroplasty is not the same as normal and is similar to the kinematics of the knee with osteoarthritis. AB - PURPOSE: It is common to assert that restoration of normal knee kinematics is essential for the best functional result after knee arthroplasty. Previous studies using the progression of the geometric centre axis have suggested that kinematics after unicompartmental arthroplasty is markedly different from the normal. For this study, the transepicondylar axis was used because this axis is closer to the flexion axis and should be a better reference for motion. The following hypothesis was tested: the transepicondylar axis would again show that the postoperative kinematics does not restore normal motion and is closer to that before replacement. METHODS: Seventeen osteoarthritic knees were tested before and after unicompartmental arthroplasty using a three-dimensional to two dimensional registration technique tracking the transepicondylar axis to calculate translation and rotation of this axis. Results were compared for the seventeen knees before and after arthroplasty and were compared to the normal knee as measured in our previous study. RESULTS: Similar motion patterns in the pre- and postoperative knees were shown but both the pre- and postoperative motion were markedly different from the normal knee. CONCLUSIONS: This result supported our hypothesis. The clinical relevance is that medial unicompartmental arthroplasty cannot restore the motion of the knee to normal in the living knee. Therefore, it would be expected that the patient for unicompartmental knee might not feel normal. It may not be possible depending on ligaments alone to restore the knee to normal, and the changes in the articular shapes and the surgical procedure may also be necessary. PMID- 24213685 TI - Outcome of arthroscopic treatment for displaced lateral clavicle fractures using a double button device. AB - PURPOSE: The purpose of this study was to assess the clinical and radiological outcomes of an arthroscopically assisted fixation of type IIB fractures using a double button device. METHODS: Twenty-one patients with a type IIB displaced fracture of the clavicle who received an arthroscopically assisted fixation using a double button device were enrolled from 2009 to 2011. Clinical assessment included the patient's demographics, cause of injury, delay before surgery, time for surgery, time before resuming work and sports, the Shoulder and Hand (QuickDASH) score, the Constant-Murley score and the visual pain analogue scale (VAS). Radiological examination consisted of anteroposterior and axillary radiographs. RESULTS: The median age of patients was 33 years (range 18-67). Mean follow-up was 35 +/- 8.9 months (range 24-51 months). The average delay before surgery was 3 days (range 1-7). At final follow-up, the mean QuickDASH score, Constant score and VAS were respectively 3.2 +/- 6 (range 0-25), 94.8 +/- 9.9 (range 62-100) and 0.5 +/- 1.2 (range 0-4). Seventeen (81 %) patients were able to resume work, including heavy manual labour, and to resume their sport activities as well. Postoperative complications included one transient adhesive capsulitis, a symptomatic acromioclavicular joint osteoarthritis and an implant failure with nonunion. Bony union was achieved in all other patients. CONCLUSION: This study has demonstrated that the arthroscopic treatment using a double button device was effective at providing a satisfactory functional outcome, minimizing the risk of complications and presenting low implant failure and low nonunion rates in patients with Neer type IIB fractures of the distal clavicle. Such results lead us to consider this minimally invasive technique as a first-choice treatment. LEVEL OF EVIDENCE: IV. PMID- 24213686 TI - Extracts of Marine cyanobacteria stimulated somatic embryogenesis of Daucus carota L. AB - Twenty five strains of marine cyanobacteria were screened for their ability to promote carrot somatic embryogenesis. Hot water extracts prepared from 21 of these strains promoted plantlet formation. Extracts from four strains increased plantlet numbers to an average of over 3.7-fold. Dialysates and nondialysates of each of these extracts also increased plantlet formation. For extracts from filamentous cyanobacteria, Nostoc sp. and Anabaena sp., dialysate was more effective (4.2-fold increase) than nondialysate (3.0-fold increase), whereas for unicellular strains Synechococcus sp. and Xenococcus sp., nondialysate was more effective (5.2-fold increase) than the dialysate (3.2-fold increase). These cyanobacterial extracts also promoted embryolike structure formation from two year old carrot cell cultures which were unable to produce plantlets using the usual methods. Here, we demonstrate the existence in marine cyanobacterial extracts of low and high molecular weight factors which strongly promote somatic embryogenesis in carrot cell cultures. PMID- 24213687 TI - Biotransformation of theobromine to caffeine in suspension and polyurethane foam immobilized coffee (Coffea arabica L.) cells. AB - Coffee (Coffea arabica L.) cells are capable of biotransforming theobromine to caffeine. In suspension culture of B2K medium, which is the "production medium" for caffeine, biotransformation was also more efficient than in DK medium. More caffeine was finally produced than calculated based on theobromine added to the medium. On the other hand, the efficiency of the biotransformation using immobilized cells in reticulate polyurethane foam cubes as a matrix varied with the phases. The biotransformation tended to be efficient under conditions which allowed the coffee cells to vigorously produce caffeine de novo. PMID- 24213688 TI - Lippia dulcis shoot cultures as a source of the sweet sesquiterpene hernandulcin. AB - The axenic shoot culture of Lippia dulcis Trev., Verbenaceae, was established on hormone-free Murashige-Skoog solid medium containing 3% sucrose. Shoots were cultured in various liquid or solid media. Woody Plant liquid medium was best for shoot multiplication, but the production of hernandulcin was relatively low. The highest hernandulcin content (2.9% dry wt) was obtained after 28 days of culture on Murashige-Skoog solid medium containing 2% sucrose. The addition of chitosan to the culture media enhanced the growth of shoots as well as the production of hernandulcin, especially with the liquid medium. PMID- 24213689 TI - Plant regeneration through somatic embryogenesis from spear callus culture of Asparagus cooperi Baker. AB - Somatic embryogenesis and plantlet formation were obtained from callus derived from the subapical region of spears of Asparagus cooperi Baker. Callus was obtained in Murashige and Skoog's medium supplemented with 1-naphthaleneacetic acid and kinetin. Increase in the concentration of potassium nitrate in subsequent subcultures resulted in the formation of embryos. Rapid multiplication of embryos was secured on transfer to a medium containing a different source of nitrogen and a low level (0.01 mg/1) of gibberellic acid. Media containing zeatin or gibberellic acid led to the formation of complete plantlets from embryos. Regenerated plants were cytologically and phenotypically stable. PMID- 24213690 TI - The effects of acetosyringone and pH on Agrobacterium-mediated transformation vary according to plant species. AB - Expiants of five plant species (Allium cepa, Antirrhinum majus, Brassica campestris. Glycine max, and Nicotiana tabacum) were co-cultivated with three Agrobacterium tumefaciens strains under different conditions to assess the effects of acetosyringone and medium pH on strain virulence. Tumours were incited on all dicotyledonous species by strains N2/73 and A281. The presence of acetosyringone during co-cultivation generally enhanced the virulence of these strains, most markedly N2/73 on A. majus and G. max, and A281 on G. max. Strain Ach5 was virulent only on N. tabacum in the absence of acetosyringone, which, when present, extended the host range to include A. majus. There was evidence to suggest that acetosyringone may suppress virulence in some strain/plant species interactions. Virulence was affected in some cases by medium pH, but there was no general effect across plant species. PMID- 24213691 TI - A rapid and efficient regeneration system for pea (Pisum sativum), suitable for transformation. AB - A method for plant regeneration via organogenesis in pea (Pisum sativum) using nodal thin cell layer segments has been developed.From 10 to 12 days old sterile pea seedlings, nodal expiants were excised from which leaves and axillary buds were removed. Shoot regeneration was consistently obtained from liquid cultures where the expiants were floated on the medium. Shoots could be harvested after two weeks and thereafter up to ten weeks and no important effect of the cultivar (Bodil, Puget, Rondo and Trille) used could be observed as far as shooting capacity was concerned.Rooting frequency of the regenerated shoots was cultivar dependent. Plantlets were obtained within 7 weeks after expiant excision. Agrobacterium tumefaciens carrying a disarmed Tiplasmid and a binary vector containing the beta-glucuronidase reporter gene, were used in cocultivation experiments on pea nodal expiants in order to obtain transgenic shoots. PMID- 24213692 TI - Plant regeneration from leaf protoplasts of Lycopersicon hirsutum f. hirsutum. AB - A protocol is described for high frequency plant regeneration from isolated leaf protoplasts of several genotypes of the wild tomato species Lycopersicon hirsutum f. hirsutum based on modified tomato protoplast culture methods. Three to four week old seedlings exposed to a low light pretreatment yielded protoplasts capable of sustained divisions on modified Lycopersicon Culture Medium. Plating efficiencies varied from 7.2%-25.9%. Colonies were transferred to modified solid greening medium after 25-35 days. Developing calli that turned bright green and produced dark green bud primordia were transferred to shoot induction medium. Shoot formation efficiencies ranged from 60%-85%. Shoots rooted easily and regenerated plants grown to complete maturity showed only transient somaclonal variation. PMID- 24213693 TI - Proline status of genetically stable salt-tolerant Brassica juncea L. somaclones and their parent cv. Prakash. AB - Three Brassica juncea L. somaclones (SR-1, -2 and -3) selected in vitro for NaCl tolerance, non-selected somacone (CP-5) and parent cv. 'Prakash' were characterized for their free proline contents in the absence of stress and as a function of increasing salt stress. In the R0 generation, 'SR-3' somaclone had ca. three times higher free proline as compared to parent 'Prakash' and other somaclones. Somaclone, SR-1, turned out to be sterile. The other somaclones were carried forward to the R2 generation after making selections for yield and yield components in the R1 generation. 'SR-3' bred true for its high proline accumulating characteristic. The somaclone 'SR-3' thus had a stable genetic variation for proline overproduction. Free proline content in 7-day-old whole seedlings and 6-week-old plant leaf tissue, increased with the increase in salt stress in all the lines but at differential rates. The magnitude of increase in free proline was much higher in 'SR-3' lines as compared to parent 'Prakash' and 'SR-2' salt-tolerant somaclones. Under salt stress, in leaf tissue, one of the 'SR-3' derived lines (SR3P6-2) accumulated as much as 269 MUmoles of free proline as compared to ca. 20 MUmoles per g dry weight in parent 'Prakash' and 'SR-2' line. It was interesting to note that there was a 'critical point' concentration of NaCl beyond which the endogenous level of free proline rose sharply. Somaclonal lines (SR3P6-2, SR2P1-2 and CP5-2) which were found to have higher salt-tolerance indices, also had higher 'critical points' as compared to the other relatively salt sensitive genotypes. The relationship between relative water content and osmotic potential of leaves under saltstress also showed a relatively higher degree of osmotic adjustment in the selected somaclones, the maximum being in SR-3 derived lines. PMID- 24213695 TI - In vitro tuberization of potato clones from different maturity groups. AB - In vitro tuberization on shoot cultures of early, mid-season, late and very late potatoes was compared. Shoots were grown at 12, 16, or 20 h photoperiods; tuberization was then induced at 0, 8 or 16 h light. In the dark, shoots from early plants initially grown at 16 h consistently set tubers earlier than the other types, whereas the very late line tuberized later and produced significantly fewer tubers. Tuber setting of mid-season plants could not be distinguished from the late type. Tuberization of the very late line was significantly hastened by shortening the photoperiod from 20 h to 12 h during the shoot growth period. Light during tuber induction delayed tuberization. This system may be useful to screen callus-derived plants for maturity, and may also be suitable for in vitro study of the photoperiodic control of tuberization. PMID- 24213694 TI - Transcription of a sorghum phosphoenolpyruvate carboxylase gene in transgenic tobacco leaves: maturation of monocot PRE-mRNA by dicot cells. AB - The expression of a Sorghum vulgare gene encoding the phosphoenol-pyruvate carboxylase involved in C4 photosynthesis has been studied after introduction into tobacco. Northern blot analysis of poly(A) mRNA from green leaves demonstrated i) the efficiency of this monocot promoter, ii) the transcription of the sorghum phosphoenol-pyruvate carboxylase mRNA with the expected size (3.4kb). These results strongly suggested that introns of this monocot gene have been excised efficiently by the dicot cells. Moreover, the presence of the sorghum phosphoenol-pyruvate carboxylase mRNA was not detected in the roots of the transformed plants, suggesting that the 2.4kb 5'-region of the gene could be sufficient to confer the tissue specific expression. PMID- 24213696 TI - In vitro propagation of Coleus forskohlii Briq. for forskolin synthesis. AB - Shoot multiplication was obtained in vitro within 20-25 d from shoot tip expiants of 30 d old aseptically germinated seedlings of Coleus forskohlii Briq., using 2 mg/1 of 6 benzylaminopurine (BA). Shoot multiplication was further enhanced with the gradual decrease in the level of BA, and its final omission after 4 months. Different auxins supplemented at the level of 0.05 mg/1 with BA did not yield better results. Seven regenerated plants showed only diploid cells in their root tips, while three plants did not. Of these, two were diploid with occasional aneuploid cells. In one plant 32 chromosomes were observed. The potential of shoot culture in vitro and use of micropropagated plants for the production of forskolin has been demonstrated. PMID- 24213697 TI - AgNO3 increases type II callus production from immature embryos of maize inbred B73 and its derivatives. AB - Incorporating 10 to 100 MUM AgNO3 into Phytagel(TM) (0.2%) solidified N6 medium containing 1 mg/L 2,4-D, 100 mg/L casamino acids and 25 mM praline (N6 1-100-25) promoted type II callus production from cultured Zea mays L. immature embryos of FRB73, B73 X A188 and a proprietary B73 BC6 genotype. Under these conditions, approximately 15, 80 and 80% of the respective FRB73, B73 X A188 and B73 BC6 explants produced type II calli after 2 to 3 weeks incubation in the dark at 28 C. In the absence of AgNO3, the type II culture response from B73BC6 immature embryos was 25% on N6 1 100-25 solidified with Phytagel(TM) (0.2%) as compared to 0% for that solidified with 0.8% agar. Duncan's medium was tested using 10 to 100 MUm AgNO3 and generally promoted type I callus initiation, although up to 6% of the explants produced type II cultures in the presence of 0.2% Phytagel(TM). Ethylene emanation rates of up to 370 and 115 nL g-1 h-1 were detected from B73 X A188 immature embryos and calli, respectively, cultured on N6 1-100-25. PMID- 24213698 TI - Morphogenetic responses of cultured cells of cambial origin of a mature tree - Dalbergia sissoo Roxb. AB - Regeneration of plantlets was achieved from cell suspension derived calli of cambial origin from mature 'elite' trees of Dalbergia sissoo. Callus proliferation occurred on the cambial tissue pieces cultured on MS medium supplemented with 2, 4-dichlorophenoxyacetic acid (2.0 mg/1) and benzylaminopurine (0.1 mg/l). Suspension cultures were obtained by transferring and agitating callus lumps in liquid medium composed as above. Aggregates of about 30 cells were plated on semi solid medium, which developed into calli. Shoot bud differentiation was observed in the calli transferred to medium devoid of auxin but containing 0.5-2.0 mg/1 benzylaminopurine. The isolated microshoots were rooted on modified MS medium containing low organic salts and auxins. PMID- 24213699 TI - Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells. AB - Genome sequencing of single cells has a variety of applications, including characterizing difficult-to-culture microorganisms and identifying somatic mutations in single cells from mammalian tissues. A major hurdle in this process is the bias in amplifying the genetic material from a single cell, a procedure known as polymerase cloning. Here we describe the microwell displacement amplification system (MIDAS), a massively parallel polymerase cloning method in which single cells are randomly distributed into hundreds to thousands of nanoliter wells and their genetic material is simultaneously amplified for shotgun sequencing. MIDAS reduces amplification bias because polymerase cloning occurs in physically separated, nanoliter-scale reactors, facilitating the de novo assembly of near-complete microbial genomes from single Escherichia coli cells. In addition, MIDAS allowed us to detect single-copy number changes in primary human adult neurons at 1- to 2-Mb resolution. MIDAS can potentially further the characterization of genomic diversity in many heterogeneous cell populations. PMID- 24213700 TI - Age estimation from fetus and infant tooth and head measurements. AB - Forensic identification comprises legal, social, ethical, and religious aspects where age detection is an important factor. When the case is a fetus or infant, recording various measurements of the body, head, and teeth is essential. The aim of this research is to evaluate the effects of different tooth and body measurements and their implications on the age estimation of fetuses and infants. This research was performed on 96 fetus and infant incisor teeth taken from 24 autopsy cases (54 % males and 46 % females) where age of the subjects were within the range of prenatal 16 weeks to postnatal 72 weeks. The data were statistically processed by regression analysis via curve estimations. According to the results, growing patterns of the head circumference (HC) and the upper central tooth measurements indicate a strong relationship, where there is no significant difference for both sexes. The growth patterns of all variables showed a linear function to a certain age (approximately 56 weeks pre-plus postnatal); the tooth height (TH) slightly increases until the closure of the root apex, and the HC gradually stabilizes in time, therefore a log-linear relation was found considerable. The results revealed eight age estimation formulas, including the combination of HC with the labiolingual, mesiodistal (MD), crown height, and TH measurements. Among these, only MD can be applied to a living. In conclusion, tooth and head measurements are found to be the main factors of age estimation formulas. PMID- 24213701 TI - Specific recognition of DNA bulge sites by in situ grown fluorescent Ag nanoclusters with high selectivity. AB - There is much demand for the development of reliable methods of bulge site recognition in DNA in order to find disease-related mutations and identify bulge sequence environments. Herein, we found that the bulge site in the DNA duplex can be used to selectively grow fluorescent silver nanoclusters (Ag NCs). The as prepared Ag NCs exhibit an emission behavior dependent on the base environment near the bulge site and can be employed in situ as a readout for specific bulge site recognition. Fluorescent signal-on sensing for the bulge site based on this inorganic fluorophore is substantially advantageous over the organic fluorophores previously used as probes, in which a fluorescent signal-off response was usually observed with context guanines flanking the bulge site. The strong dependence of the fluorescent Ag NCs' formation on the bases surrounding the bulge site is successfully used to identify the bulge environment near the codon 177 of cancer suppression gene p53. We expect that bulge site-determined Ag NC formation is very likely to be developed into a simple method for bulge site recognition with high selectivity and sensitivity. PMID- 24213702 TI - The potential impact of geological environment on health status of residents of the Slovak Republic. AB - In order to assess the potential impact of the geological environment on the health of the population of the Slovak Republic, the geological environment was divided into eight major units: Paleozoic, Crystalline, Carbonatic Mesozoic and basal Paleogene, Carbonatic-silicate Mesozoic and Paleogene, Paleogene Flysch, Neovolcanics, Neogene and Quaternary sediments. Based on these geological units, the databases of environmental indicators (chemical elements/parameters in groundwater and soils) and health indicators (concerning health status and demographic development of the population) were compiled. The geological environment of the Neogene volcanics (andesites and basalts) has been clearly documented as having the least favourable impact on the health of Slovak population, while Paleogene Flysch geological environment (sandstones, shales, claystones) has the most favourable impact. The most significant differences between these two geological environments were observed, especially for the following health indicators: SMRI6364 (cerebral infarction and strokes) more than 70 %, SMRK (digestive system) 55 %, REI (circulatory system) and REE (endocrine and metabolic system) almost 40 % and REC (malignant neoplasms) more than 30 %. These results can likely be associated with deficit contents of Ca and Mg in groundwater from the Neogene volcanics that are only about half the level of Ca and Mg in groundwater of the Paleogene sediments. PMID- 24213703 TI - Seasonal concentrations of lead in outdoor and indoor dust and blood of children in Riyadh, Saudi Arabia. AB - Because detrimental effects of exposure to lead (Pb) on human health have been observed, we previously investigated concentrations of Pb in water supplies and blood of adult residents of Riyadh, Saudi Arabia. The objectives of the present study were to: (1) examine seasonal rates of deposition of Pb in dust in several areas of Riyadh city, (2) measure concentrations of Pb in both outdoor and indoor dust, (3) compare concentrations of Pb in dust in Riyadh with those reported for other cities, and (4) quantify Pb in blood of children living in Riyadh. Mean, monthly deposition of PB in outdoor dust was 4.7 * 10(1) +/- 3.6 tons km(-2), with a mean Pb concentration of 2.4 * 10(2) +/- 4.4 * 10(1) MUg/g. Mean, monthly deposition of Pb in indoor dust was 2.7 +/- 0.70 tons km(-2), with a mean concentration of 2.9 * 10(1) +/- 1.5 * 10(1) MUg Pb/g. There was a significant (P < 0.01) correlation between concentrations of Pb in outdoor and indoor dust. There was no correlation between concentrations of Pb in indoor dust and that in blood of children of Riyadh, whereas there was a weakly significant (P < 0.05) correlation between concentrations of Pb in outdoor dust and that in blood of children. The mean (+/-SD) concentration of Pb in blood of children in Riyadh was 5.2 +/- 1.7, with a range of 1.7-1.6 * 10(1) MUg/dl. Concentrations of Pb in blood of 17.8 % of children in Riyadh were greater than 10 MUg/dl, which is the CDC's level of concern. PMID- 24213704 TI - Changes in nutrient ratios and phytoplankton community structure caused by hydropower development in the Maotiao River, China. AB - Reservoirs created for hydropower production have become an important feature impacting a river. Understanding the effects of river impoundment on the downstream environment is critical to decision-making for water resource protection. The changes caused by impoundment are changes in water quality and the resulting effect on the phytoplankton community structure. The impacts caused by a series of reservoirs along a river are still not well understood. In this study, we conducted an investigation of five reservoirs along the Maotiao River, China. We found that a series of impoundments plays a role in decreasing the phytoplankton biomass in downstream reservoirs. Within the studied area, nitrogen is not a limiting factor for phytoplankton growth. The ratio of silicon to phosphorus (Si:P) can become a major factor in the regulation of phytoplankton community structure. The Si:P ratio increased from upstream to downstream reservoirs, causing a concurrent increase in the percentage of Bacillariophyta, particularly during the winter. In addition, our results indicate that the creation of dams eliminates Si limitation downstream. PMID- 24213705 TI - Heavy metal concentrations in feathers of common loons (Gavia immer) in the Northeastern United States and age differences in mercury levels. AB - Feathers serve as a useful, non-destructive approach for biomonitoring some aspects of environmental quality. Birds can eliminate over 90% of their body burden of mercury by sequestration in growing feathers, and they molt their feathers at least annually. Thus mercury concentrations should not vary in avian feathers as a function of age. We tested the null hypothesis that there are no age differences in the concentrations of mercury, lead, cadmium, selenium, copper, chromium and manganese in the feathers of immature and adult common loons Gavia immer from the Northeastern United States where the species is declining. Adults had significantly higher mean levels of mercury (20245 ppb) than immature loons (9677 ppb), but there were no age-related differences for other elements. Even with the small number of immatures, females had significantly higher levels of mercury than males, although the gender difference was not significant for adults. PMID- 24213706 TI - Value functions for environmental pollutants: A technique for enhancing the assessment of expert judgements. AB - This paper presents a new procedure to assess value functions for environmental pollutants. It has been particularly designed for eliciting expert-based value functions for pollutant substances. The main features of the model are the possibility to integrate direct and indirect assessment techniques, the possibility to make explicit assessment uncertainties and to avoid forcing quantitative judgements. The main aim of the procedure is to improve the reliability of the assessment but also to make the expert's task easier by using qualitative judgements more frequently. The procedure has been developed especially for soil pollutants, for which an application is described. PMID- 24213707 TI - Performance of two artificial substrate samplers for macroinvertebrates in biological monitoring of large and deep rivers and canals in Belgium and The Netherlands. AB - Harmonization exercises organized by the European Communities in the 1970s on biological water assessment methods for running waters, because the usual methods were difficult or impossible to apply, explicitly stressed the need for development of standardized sampling procedures for monitoring large and deep rivers and canals. To meet this objective, an extensive monitoring campaign was organized in Belgium and The Netherlands to test the efficiency of artificial substrates colonized by macroinvertebrates as an alternative for natural communities sampled with a handnet. Two types of artificial substrates were tested: a Belgian substrate, composed of a plastic netting filled with medium sized pieces of brick, and a Dutch substrate consisting of a stainless steel box filled with marbles. The collected biocoenoses were compared qualitatively and quantitatively. Water quality was assessed by means of several biotic indexes. The results show that both the Belgian and the Dutch artificial substrate sampler can replace the usual samples obtained by means of a handnet, and provide a correct assessment. A major drawback of the use of artificial substrates in uncontrolled monitoring sites remains the unforeseen losses. For that reason the cost price of the substrates may have to be considered when making a selection. PMID- 24213708 TI - Evaluation of filter-based aerosol measurements during the 1987 Southern California Air Quality Study. AB - The Southern California Air Quality Study (SCAQS) was conducted during the summer and fall of 1987 to assess the causes of elevated ozone and suspended particulate matter concentrations in California's South Coast Air Basin (SoCAB). Extensive gaseous (i.e. nitric acid, ammonia, sulfur dioxide) and particle (i.e. PM2.5 and PM10 mass, elements, ions, carbon) measurements were acquired for 11 days during the summer at nine locations, and six days during the fall at six locations. Outliers were identified so that they could be excluded from further statistical analyses. Carbon and elemental measurements were found to be negatively biased by ~ 20% owing to inhomogenous aerosol deposits on the SCAQS filters and analysis methods which were applied to a portion of the filters. These biases seem relatively consistent, however, and should not affect conclusions drawn from data analysis efforts if they are appropriately considered. Significant fractions (30 60%) of ammonium nitrate volatilized during the summer when temperatures were higher. Less than 10% typically volatilized during the fall when temperatures were lower. Anion/cation balances support the accuracy and precision estimates of the nitrate, sulfate, and ammonium measurements. Coarse particle sulfate was generally low, while coarse particle nitrate was most pronounced at the coastal sites.This paper documents SCAQS filter-based aerosol measurement methods, and evaluates the accuracy, precision, and validity of the data set. Various comparisons were made for: (1) PM2.5/PM10 ratios for mass and major chemical species; (2) sum of chemical species versus measured mass; (3) sulfate versus sulfur ratios; (4) PM2.5 particulate nitrate versus nitric acid-denuded nitrate; and (5) anion/cation balances. The measurement and evaluation techniques presented in this paper serve as a guideline for other data analysis and modeling studies. PMID- 24213709 TI - Qualitative time trend analysis of ground water monitoring networks : An example from The Netherlands. AB - The detection of significant (short-term) time trends is one of the major goals of ground water monitoring networks. These trends can be used to recognize active geochemical processes and potential environmental threats. This paper presents a case history of time trend analysis on macrochemical parameters of ground water quality. It shows the difficulties and traps that are generally encountered in such studies. The data used originated from the Dutch National Groundwater Quality Monitoring Network. This network is operative since 1979, and keeps track of the ground water composition at 350 locations at two depths (ca. 10 and 25 m below surface; general density, one location per 100 km(2)). Prior to the trend analysis the data set was divided into geochemically homogeneous groups using fuzzy c-means clustering. Each group represents a specific ground water type, characterized by a distinct source (seawater, surface water or precipitation) and a unique combination of dominant geochemical processes (e.g. mineralization of organic matter, carbonate dissolution and cation exchange).To study trends qualitatively, the concentrations of the various macro-constituents in ground water are correlated with time of sampling. The nonparametric and outlier insensitive Spearman rank correlation coefficient is computed per well screen. A frequency distribution of correlation coefficients is formed by combining the Spearman correlation coefficients of all individual wells within a homogeneous group. This distribution is tested for trends against the appropriate theoretical distribution of zero correlation by use of the Kolmogorov-Smirnov one-sample test. The type of trend is derived from the shape of the distribution.Most ground water types show statistically significant qualitative trends, of which many, however, are caused by changes in the sampling and analytical procedures over the monitoring period. After elimination of differences in limits of detection for NO3, total-P, and NH4, most trends in these compounds disappeared. In some water types trends for alkalinity, apparent trends for pH, Ec, and total-P are caused by variations in the laboratory practice, e.g. varying storage procedures, leading to erroneous analyses. Other parameters showed statistically significant trends, related to geochemical processes.The most interesting and most substantial trends are observed in the water type characterized by infiltrating rainwater with agricultural pollutants. In this water type the lowering ground water table induces lower rates of evapotranspiration, giving lower concentrations in time of conservative parameters (Cl, Na, Ca). The aerated zone is enlarged, resulting in increased oxidation of organic material, less efficient nutrient (NO3, K) uptake by plant roots, leading to increased ground water concentrations of nutrients. In other water types trends are quantitatively small. However, trends are not necessarily linear, and all should be closely monitored in future. PMID- 24213710 TI - Catalytic activity and immunochemical quantification of hepatic cytochrome P-450 in beta-naphthoflavone and isosafrol treated rainbow trout (Oncorhynchus mykiss). AB - In addition to catalytical assays, immunochemical techniques have recently been employed to measure induction of the cytochrome P-450 (P450) monooxygenase system in fish with polyaromatic hydrocarbons (PAH). In the present study, polyclonal antibodies were raised against rainbow trout P450IA1. Levels of rainbow trout P450IA1 determined using protein blotting- and ELISA procedures were compared with levels of 7-ethoxyresorufin-O-deethylase (7-EROD) activity in liver microsomes from rainbow trout. These comparisons showed that values of P450A1 were positively correlated (r=0.99 and r=0.97) with 7-EROD activities. In addition, the effects of isosafrol (ISF) or beta-naphthoflavone (betaNF) treatments on P450 levels in rainbow trout liver were investigated using immunochemical and catalytical methods. ISF treatment induced 7-EROD activity as well as 7-methoxycoumarin-O-demethylase-, 7-ethoxycoumarin-O-deethylase-, 7 propoxy-coumarin-O-depropylase and 7-butoxycoumarin-O-debutylase activities, although to a lesser extent, compared with the betaNF treatment. In contrast, immunochemical quantification of rainbow trout P450IA1 protein revealed a slightly different pattern. ISF appeared to be a weak inducer of P450IA1 in rainbow trout compared with betaNF. In addition, the degree of inhibition of 7 alkoxycoumarin-O-dealkylase activities in ISF microsomes differed from that measured in control- and betaNF microsomes. The discrepancies between catalytic and immunochemical estimates of rainbow trout P450IA1 in ISF treated fish in addition to differencs between specific inhibitory pattern by specific polyclonal antibodies raised against rainbow trout P450IA1, indicate that important differences exists between the responses induced by betaNF- and ISF treatments in the rainbow trout liver. PMID- 24213711 TI - Incorporation of yolk fatty acids into body lipids of goldfish (Carassius auratus L.) larvae raised at two different temperatures. AB - In five separate experiments, eggs from a single female goldfish were fertilized at 20 degrees C. They were incubated at 22 degrees C for 6 hours, after which some of the eggs were transferred to 13 degrees C. When a defined post-hatch developmental stage was reached, lipid extracts were prepared from larvae, both with yolk sacs intact and after removal of the yolk sac by dissection. Other larvae were sampled at yolk exhaustion. Gas chromatographic analysis of fatty acid profiles revealed that larvae incorporated 16:0, 18:0, 20:4 (n-6) and 22:6 (n-3) into their tissues in proportions higher than those present in the eggs from which they were derived. At 22 degrees C, these trends were particularly apparent at yolk exhaustion. At 13 degrees C, proportions of polyunsaturated fatty acids in the bodies of newly hatched larvae were higher than those in the 22 degrees C larval bodies. Monounsaturated fatty acids were preferentially depleted during development, especially in larvae from high quality eggs. No dependence of egg quality, as assessed by larval viability at 22 degrees C, on total egg lipid mass or fatty acid composition was found. Larvae from the lowest quality eggs showed a reduced preference for incorporation of (n-3) polyunsaturated fatty acids into their tissues. PMID- 24213712 TI - Administration of gulonolactone does not evoke ascorbic acid synthesis in teleost fish. AB - Evidence is presented that for common carp (Cyprinus carpio L.), intraperitoneal injection of L-gulonolactone, a precursor of ascorbic acid synthesis in the D glucuronic acid pathway, does not result in an increased concentration of ascorbate in tissue. Control fish injected with an equimolar amount of ascorbic acid have shown a significant increase in ascorbic acid concentration in the kidney, hepatopancreas, plasma and spleen. The ascorbate status in the carp body,i.e., the ascorbate nutritional history, produced significant differences in ascorbate withdrawal from circulation and probably in the catabolic rate. Acute fasting decreased ascorbate uptake into tissues as compared to fish fed a diet lacking ascorbate. Intraperitoneally injected ascorbate affects common carp being fed a diet containing 295 mg of total ascorbic acid kg(-1) by causing tissue to become saturated with vitamin C, similar to the tissues in the group undergoing acute fasting. There was no gulonolactone oxidase activity in the hepatopancreas of the common carp. These results suggest that the metabolic rate induced by feeding is the primary factor regulating ascorbate requirement. PMID- 24213713 TI - Plasma levels of insulin, glucagon and glucagon-like peptide in salmonids of different weights. AB - Plasma levels of insulin in rainbow trout,Oncorhynchus mykiss, Atlantic salmon,Salmo salar, and Pacific coho salmon,Oncorhynchus kisutch and plasma circulating levels of glucagon and glucagon-like peptide, in rainbow trout and Atlantic salmon, were measured by homologous radioimmunoassays. Hormonal levels were compared against the average body weight of the same group of fish. Plasma insulin levels were significantly correlated (r=0.56, 0.46 and 0.42 respectively) with body weight in all three salmonid species. Moreover, rainbow trout from fast growing families had significantly higher (p<0.005) plasma insulin levels than did fish from slow-growing families. Plasma titres of glucagon and glucagon-like peptide were always lower than insulin titres and did not correlate with body weight. PMID- 24213714 TI - Plasma kinetics of ingested tritiated estradiol and the influence on estradiol plasma levels in the cultured Siberian sturgeonAcipenser baeri. AB - Plasma kinetics of tritiated estradiol (E2) were studied in the Siberian sturgeonAcipenser baeri in order to explain the large amount of E2 found in plasma of 4, 5 and 10-year-old cultured males. This work presents two approaches. The first is based on a single ingestion of(3)H-labelled E2, which allowed us to plot model curves of resorption and elimination processes. The second deals with chronic ingestion of(3)H-labelled E2 during a five day period, twice a day, based on a rhythm copied from the feeding practice on a fish farm. Three different doses were tested, based on the amount present in fish diets. Oral administration of E2 to sturgeon leads to E2 accumulation and a saturation of the metabolic processes generally involved in the elimination of aromatic xenobiotics. An explanation of this progressive accumulation of E2 in sturgeon plasma has to take into account the steroid binding proteins. Their synthesis could be induced by the orally administrated E2 and protect it from metabolism. PMID- 24213715 TI - Hormonal regulation of metabolism in hepatocytes of the ureogenic teleostopsanus beta. AB - Short-term exposure of isolated toadfish hepatocytes to high concentrations (100 nM) of glucagon, glucagon-like peptide (GLP) or epinephrine significantly increases the rate of lactate gluconeogenesis (1.3-fold) and glycogenolysis (5- to 7-fold). Half-maximal responsiveness to GLP is reached at about 2 nM for gluconeogenesis and 6 nM for glycogenolysis, while the value for glycogenolysis activated by catfish glucagon is 28 nM. Cells do not to respond to 5 nM epinephrine. Norepinephrine, urotensin II and leucine-enkephalin, each applied at 100 nM, increase the rate of glycogenolysis by 1.3 to 1.5-fold. All other hormones tested (vasotocin, isotocin, VIP, methionine-enkephalin, ovine prolactin, beta-endorphin, APY, salmon insulin) failed to affect metabolic flux through glycogenolysis or gluconeogenesis. None of the hormones altered the rate of urea synthesis or the rate of lactate oxidation by hepatocytes. Although toadfish hepatocytes are responsive to hormonal stimuli, they do not appear to be a useful model to study evolutionary trends in short-term hormonal regulation of urea synthesis. However, the obvious differences in mechanisms of control of urea synthesis in this species compared with ureogenic amphibians and mammals open an intriguing avenue for research. PMID- 24213716 TI - Plasma insulin, glucagon, glucagon-like peptide and glucose levels in response to feeding, starvation and life long restricted feed ration in salmonids. AB - Plasma insulin, glucagon, glucagon-like peptide (GLP) and glucose were measured in samples taken from rainbow trout,Oncorhynchus mykiss. (1.5 years of age) before feeding and at selected times up to 9 days after feeding. The feed contained 21.7% carbohydrate (65% digestibe) in the dry matter. The fish responded to feeding with an elevated plasma insulin level (p<0.005) 0.5 h post feeding, which may account for the unchanged plasma glucose levels. Twentyfour hours after feeding, plasma insulin level had returned to prefeeding levels, while 4-9 days after feeding, a significant reduction compared to pre-feeding levels was observed (p<0.001). During this period plasma glucose levels remained unchanged. The corresponding plasma glucagon or GLP levels showed no significant elevation in response to starvation, the plasma GLP concentration was even significantly reduced on days 4-9 post-feeding (p<0.01-0.001).Atlantic salmon,Salmo salar, (3.5 years of age) fed a calculated satiation ration (RL=100) throughout their lifetime had, in addition to a higher body weight, significantly higher plasma insulin (p<0.005) glucagon (p<0.0001) and GLP levels (p<0.0001) than fish fed half the satiation ration. The plasma glucose levels were, however, not significant different between the groups. PMID- 24213717 TI - Influence of temperature on the proliferative response of rainbow trout gonadal fibroblasts to cortisol and RU 486. AB - The rainbow trout gonadal cell line, RTG-2, which survives temperatures from 0 to 28 degrees C and proliferates at 5 to 26 degrees C, responded to cortisol from 28 degrees C to 0 degrees C by influencing [(3)H]-thymidine incorporation into DNA. Over the normal temperature range of rainbow trout, 10-22 degrees C, cortisol inhibited [(3)H]-thymidine incorporation. The antiglucocorticoid RU 486 had no effect on [(3)H]-thymidine incorporation at these temperatures and blocked the response to cortisol. Another antiglucocorticoid RU 362 also had no effect but was less effective in blocking the cortisol response. During incubation at 28 degrees C this inhibitory response to cortisol was detected inconsistently during the first 24 h but was observed consistently during the second 24 h. At 0 degrees C, cortisol and RU 486 had no effect during short treatments, but a 60 h exposure to either steroid stimulated [(3)H]-thymidine incorporation over a 48 h labelling period. These results suggest that temperature shifts between 10-22 degrees C, do not change the direction of a response to cortisol and support the use of the upper portion (20-22 degrees C) of the temperature range for studies on salmonid cells in culture. PMID- 24213718 TI - Biological actions of atrial natriuretic factor in flatfish. AB - Flounder adapted to seawater were chronically cannulated and received a single i.v. injection of either saline (control) or 10 ug/kg b.w. of human ANF. Compared to controls, ANF significantly reduced (p<0.001) mean arterial blood pressure; full recovery was evident after 4 hours. Blood samples taken at intervals after saline or ANF injection showed that ANF caused a marked increase of 33.7 ug/100 ml in plasma cortisol concentration (p<0.001) 5 hours post injection. The rate of recovery of(22)Na in seawater after a single i.v. injection of 14*10(6) cpm/kg(22)NaCl was significantly increased (p<0.01) following ANF injection compared to controls suggesting that ANF stimulates Na(+) efflux. This observation was confirmed in plaice and dab. The steroidogenic action of ANF and its ability to promote Na(+) efflux are discussed in relation to its potential osmoregulatory role in teleost fish. PMID- 24213719 TI - Erythrocyte fractionation by velocity sedimentation and discontinuous density gradient centrifugation. AB - Investigation of development, maturation and senescence in fish red blood cells depends on effective separation methods. Preliminary to initiation of studies of this type the erythrocytes of goldfish,Carassius auratus, and rainbow trout,Oncorhynchus mykiss, were fractionated by velocity sedimentation at unit gravity or discontinuous Percoll density gradient centrifugation in an attempt to separate and characterize enriched populations of juvenile and mature cells. Cytomorphological variables were assessed by microphotography (trout) and image analysis (goldfish). In both species velocity sedimentation led to fractions which were readily recognized in terms of mean length (maximum cell chord), area and shape (chord ratio, form factor), and sufficiently enriched for some types of study. Density gradient centrifugation also lead to cell separation. However, fractional densities appeared to reflect nuclear rather than cellular morphologies, and the fractions obtained were not readily categorized in relation to stage of development. Accordingly, at the present time, velocity sedimentation appears to offer the more suitable means for fractionating red cells for investigation of maturation and aging processes. PMID- 24213720 TI - Aberrant SERCA3 expression during the colorectal adenoma-adenocarcinoma sequence. AB - Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 is involved in calcium mobilization from the endoplasmic reticulum into the cytosol and is closely linked to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding and carcinogenesis. In order to elucidate the role of SERCA3 in colorectal carcinogenesis and subsequent progression, its expression was examined using immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adjacent non-neoplastic mucosa (NNM) and adenoma, and metastatic carcinoma in lymph node and liver. Colorectal carcinoma tissue and cell lines were assessed for SERCA3 expression by western blotting or RT-PCR, respectively. SERCA3 was distinctively expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM 12, SW480, SW620 and WiDr cells at both the mRNA and protein levels. SERCA3 mRNA expression was low in carcinoma when compared to that in matched NNM by quantitative PCR (P<0.05), while the converse was true by ISH. Lower expression of SERCA3 was immunohistochemically observed in colorectal carcinoma when compared to that in NNM and adenoma (P<0.05). In contrast, primary carcinoma showed high SERCA3 expression when compared to that in metastatic carcinoma in lymph node or liver by IHC (P<0.05). Immunohistochemically, SERCA3 expression was negatively related to lymphatic invasion, but not with age, gender, depth of invasion, venous invasion, lymph node metastasis, distant metastasis, TNM stage, degree of differentiation or survival rate (P>0.05). There was a positive relationship between SERCA3 expression and serum CEA levels in the carcinoma patients (P<0.05). Cox's proportional hazards model indicated that depth of invasion and distant metastasis are independent prognostic factors for overall colorectal carcinomas (P<0.05). These findings suggest that aberrant SERCA3 expression is closely linked to the adenoma-adenocarcinoma sequence and progression of colorectal carcinomas. PMID- 24213721 TI - Effects of species evenness and dominant species identity on multiple ecosystem functions in model grassland communities. AB - Ecosystems provide multiple services upon which humans depend. Understanding the drivers of the ecosystem functions that support these services is therefore important. Much research has investigated how species richness influences functioning, but we lack knowledge of how other community attributes affect ecosystem functioning. Species evenness, species spatial arrangement, and the identity of dominant species are three attributes that could affect ecosystem functioning, by altering the relative abundance of functional traits and the probability of synergistic species interactions such as facilitation and complementary resource use. We tested the effect of these three community attributes and their interactions on ecosystem functions over a growing season, using model grassland communities consisting of three plant species from three functional groups: a grass (Anthoxanthum odoratum), a forb (Plantago lanceolata), and a N-fixing forb (Lotus corniculatus). We measured multiple ecosystem functions that support ecosystem services, including ecosystem gas exchange, water retention, C and N loss in leachates, and plant biomass production. Species evenness and dominant species identity strongly influenced the ecosystem functions measured, but spatial arrangement had few effects. By the end of the growing season, evenness consistently enhanced ecosystem functioning and this effect occurred regardless of dominant species identity. The identity of the dominant species under which the highest level of functioning was attained varied across the growing season. Spatial arrangement had the weakest effect on functioning, but interacted with dominant species identity to affect some functions. Our results highlight the importance of understanding the role of multiple community attributes in driving ecosystem functioning. PMID- 24213722 TI - The third dimension of bat migration: evidence for elevational movements of Miniopterus natalensis along the slopes of Mount Kilimanjaro. AB - Bats are important ecosystem service providers, and therefore most relevant for both lowland and highland habitats, particularly in the tropics. Yet, it is poorly understood to what extent they perform large-scale movements, especially movements along mountain slopes. Here, we studied the movement ecology of the potentially migratory species Miniopterus natalensis at Mount Kilimanjaro in Tanzania. We analysed stable isotope ratios of C (delta(13)C), N (delta(15)N) and H (delta(2)H) in keratin of sedentary frugivorous and insectivorous bats captured between 800 and 2,400 m above sea level to establish elevational gradients of stable isotope ratios in consumer tissues. We expected correlations between stable isotope ratios of the non-exchangeable portion of H in fur keratin and the elevation of capture site, but not necessarily for delta(13)C and delta(15)N. Yet, in bats of both feeding ensembles, we found delta(15)N of fur keratin to correlate positively with the elevation of capture sites but not delta(2)H. In frugivorous bats, delta(13)C increased with increasing capture elevation as well. By looking at intra-individual variation of delta(13)C and delta(15)N in fur keratin and wing membrane tissues of sedentary Rhinolophus cf. clivosus and of the potentially migratory species M. natalensis, we gathered evidence that M. natalensis migrates seasonally between low and high elevations along the slopes of Mount Kilimanjaro. Finally, based on an isoscape origin model we estimated that M. natalensis captured before and after the cold period at around 1,800 m above sea level originated from around 1,400 m a.s.l. or lower. Thus, we received convergent results in support of seasonal elevational movements of M. natalensis, probably in search for cold hibernacula at higher elevations of Mount Kilimanjaro. PMID- 24213723 TI - Tuning inter-dot tunnel coupling of an etched graphene double quantum dot by adjacent metal gates. AB - Graphene double quantum dots (DQDs) open to use charge or spin degrees of freedom for storing and manipulating quantum information in this new electronic material. However, impurities and edge disorders in etched graphene nano-structures hinder the ability to control the inter-dot tunnel coupling, tC, the most important property of the artificial molecule. Here we report measurements of tC in an all metal-side-gated graphene DQD. We find that tC can be controlled continuously about a factor of four by employing a single gate. Furthermore, tC, can be changed monotonically about another factor of four as electrons are gate-pumped into the dot one by one. The results suggest that the strength of tunnel coupling in etched graphene DQDs can be varied in a rather broad range and in a controllable manner, which improves the outlook to use graphene as a base material for qubit applications. PMID- 24213724 TI - Copper and resveratrol attenuates serum catalase, glutathione peroxidase, and element values in rats with DMBA-induced mammary carcinogenesis. AB - In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4.5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p < 0.05) or copper plus resveratrol (p < 0.001) in comparison with the control groups that received the same diets. In cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p < 0.001). The mean serum copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p < 0.001). The characteristic changes in iron content and the zinc/copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research. PMID- 24213725 TI - Comparison between open and arthroscopic procedures for lateral clavicle resection. AB - PURPOSE: Arthroscopic lateral clavicle resection (LCR) is increasingly used, compared to an open approach, but literature does not clearly indicate which approach is preferable. The goal of this study was to compare function and pain between patients who underwent lateral clavicle resection using an open approach and patients treated using an arthroscopic approach. METHODS: Patients who underwent LCR between January 2008 and December 2011 were reviewed. After exclusion, 149 shoulders (143 patients) were eligible for analysis: 41 open and 108 arthroscopic. Disabilities of arm, shoulder and hand (DASH) questionnaire and visual analogue scale (VAS) score were used to assess shoulder function and pain. Complications, operative time, length of hospitalization and resection distance were compared. RESULTS: At a mean follow-up of three years, patients in the open group had significantly less pain by VAS (mm) (Mdn 10, IQR 23) compared with arthroscopic patients (Mdn 20, IQR 50) (p = 0.036). Operative time (minutes) was significantly less for the open approach (Mdn 24.0, IQR 12) compared with arthroscopic (Mdn 38.0, IQR 15) (p < 0.001). Resection distance (mm) was larger for the open approach (Mdn 7.1, IQR 7.0) compared with the arthroscopic approach (Mdn 3.2, IQR 3.1) (p = 0.006), but was not associated with outcome. No significant differences were found for DASH score, complication rate or length of hospitalization. CONCLUSIONS: Both arthroscopic and open approaches for LCR provide excellent outcome in patients with acromioclavicular pain. Less residual pain was found for the open approach, which has shorter operating time and is likely more cost effective. PMID- 24213726 TI - Strain differences in hemoglobin polymorphism, oxygen consumption, and blood oxygen equilibria in three hatchery broodstocks of arctic charr,Salvelinus alpinus. AB - Hemoglobin polymorphism, standard oxygen consumption, and blood oxygen equilibria were examined in three stocks of Arctic charr,Salvelinus alpinus, originating from the central Arctic (Nauyuk Lake) and Labrador (Fraser River) regions of Canada and from Norway (Storvatn) and maintained at the Rockwood Experimental Fish Hatchery in Gunton, Manitoba. Ten hemoglobin isomorphs were identified in the blood of adult charr by starch gel electrophoresis at pH 8.6. Five anodic isomorphs were found in all charr. The stocks differed, however, in the occurrence an relative concentrations of five cathodic isomorphs. Nauyuk Lake charr exhibited two hemoglobin phenotypes based on the presence of either three (3-C) or five (5-C) cathodic isomorphs whereas the Labrador charr were uniformly the 5-C phenotype and the Norwegian charr were uniformly the 3-C phenotype. Physiologically, the Labrador and Norwegian charr exhibited similar standard rates of oxygen consumption over a weight range of 0.5 to 50 g and similar blood oxygen equilibria. Charr from Nauyuk Lake exhibited higher standard oxygen consumption rates at weights above 10 g, and blood with both a higher oxygen affinity and a larger Bohr shift than the other two charr strains. All charr strains exhibited very low residual oxygen levels. PMID- 24213727 TI - Effects of exercise-training on cardiac performance and muscle enzymes in rainbow trout,Oncorhynchus mykiss. AB - Rainbow trout,Oncorhynchus mykiss, were exercise-trained for 18 hours per day over 28 days at water velocities up to 60% of their measured Ucrit. Anin situ perfused heart preparation was used to compare maximum cardiac performance between control and trained fish. Trained fish had a larger stroke volume at a given filling pressure, as well as an 18% higher cardiac output and a 25% greater maximum power output. These observations indicate that exercise training in rainbow trout improved maximum cardiac performance. Adrenaline produced positive inotropic and chronotropic effects on the perfused heart, but exercise training did not alter these stimulatory effects. Maximal activities of citrate synthase (CS), B-hydroxyacyl CoA dehydrogenase (HOAD), glutamate dehydrogenase (GDH) and carnitine palmitoyl transferase (CPT) were measured in cardiac and skeletal muscles. CS, HOAD and GDH increased in red and white skeletal muscle as a result of training. Training also increased GDH activity in the endocardium and epicardium, and increased HOAD in the epicardium. While the training regime did not result in a statistically significant increase in Ucrit and produced a decrease in the condition factor of the fish, other training effects were clearly evident. Furthermore, significant correlations were observed between Ucrit and the maximal activities of GDH and HOAD. PMID- 24213728 TI - Extracellular fluid volume measurements in tissues of the rainbow trout (Oncorhynchus mykiss)in vivo and their effects on intracellular pH and ion calculations. AB - Extracellular fluid volume (ECFV) estimates were determined in various tissues and whole body of resting, chronically cannulated rainbow trout (Oncorhynchus mykiss). Fish were infused with(14)C-inulin,(3)H-polyethylene glycol (PEG, M.W. 4000),(3)H-mannitol, or(14)C-mannitol, and values of ECFV determined from tissue: plasma water distribution ratios after 6 h or 13 h equilibration. Overall,(3)H PEG provided the most conservative and reliable estimates after 13 h equilibration, with ECFV values in the order: brain < white muscle < red muscle < liver < heart < gill tissue.(14)C-inulin yielded generally similar values to(3)H PEG at 13 h, but probably overestimated ECFV in liver.(3)H-mannitol and(14)C mannitol spaces were similar to each other and far greater than(3)H-PEG or(14)C inulin values in most tissues.(3)H-mannitol values increased significantly between 6 h and 13 h, in contrast to(14)C-inulin. Mannitol clearly overestimated ECFV in liver and gill, and probably also heart and whole body, but may have provided more realistic estimates in brain due to better penetration of the blood brain barrier. The Cl(-)/K(+) space technique overestimated ECFV in gills, but was satisfactory in white muscle. Measurements and model calculations evaluated sources of error in intracellular pH (by(14)C-DMO) and ion determinations. Trapped red cells in the gills have negligible influence. Errors in ECFV are much more influential in a tissue with a high ECFV (gills) than a low ECFV (white muscle).(3)H-PEG is the marker of choice for intracellular pH determinations. However, even when(3)H-PEG is used, the potential for absolute errors in intracellular ion concentrations remains high. PMID- 24213729 TI - Plasma membrane of trout spermatozoa: I. Isolation and partial characterization. AB - The plasma membrane from spermatozoa of rainbow trout was isolated by four techniques: sonication, hypotonic shock, mechanical homogenization after freeze thawing, and nitrogen cavitation, in combination with continuous sucrose gradient centrifugation. Nitrogen cavitation (900 PSI, 20 min equilibration at 4 degrees C) was the most effective technique.Following nitrogen cavitation, four bands were recovered in the sucrose gradient at densities ~ 1.03, 1.05, 1.09 and 1.15 g/ml. Electron microscopy revealed membrane vesicles of various sizes in bands 1 to 3, while enzyme analysis revealed a 3.9 to 5.5-fold enrichment in 5' nucleotidase and little contamination by lactate dehydrogenase (cytosol) and succinic dehydrogenase (mitochondria). Lipid analysis of bands 1 and 2 indicated a 6 to 7-fold enrichment in cholesterol and a cholesterol: phospholipid ratio of 0.59-0.70. Seven classes of phospholipids were present in bands 1-3 with no significant differences observed among bands. These data indicate that the vesicles (in bands 1 and 2) obtained after nitrogen cavitation are primarily plasma membranes. Membranes in band 3 appear to be slightly contaminated with nuclear membranes.Most of the plasma membrane proteins were acidic to neutral. The 2 main membrane proteins were 42 and 30 Kilodaltons. PMID- 24213730 TI - The cytochrome P450 system of atlantic salmon (Salmo salar): I. Basal properties and induction of P450 1A1 in liver of immature and mature fish. AB - The major components of the cytochrome P450 (P450) system in liver microsomes of Atlantic salmon were studied using spectrophotometric, catalytic and immunochemical techniques. In juvenile fish sampled during the winter season, high basal activities of 7-ethoxyresorufin O-deethylase (EROD) were found. The Km for 7-ethoxyresorufin was 0.4 uM, and Vmax 1.23 nmol/min/mg protein in juvenile fish. In mature fish sampled from the same group of fish in December, EROD activity was barely detectable (20-30 pmol/min/mg protein). Treatment with the P450 1A1 inducer beta-naphthoflavone (BNF) resulted in almost 2-fold induction of total P450, and 30-40-fold induction of EROD activity in immature fish. A similar fold increase was seen in mature fish. The differences in EROD activity between untreated and BNF-treated fish, was accompanied by similar differences in a P450 1A1 cross-reacting protein (Mr=58,000 D) in immunochemical studies using rabbit anti-cod P450 1A1 IgG. However, judging from these studies, the levels of P450 1A1-protein in mature salmon far exceeded those accounted for by the measured EROD activity in comparison to immature fish (both before and after BNF treatment), indicating inhibiting effects of sex steroids on the measured activity. This effect was not seen on 7-ethoxycoumarin O-deethylase activity. A long-term storage experiment indicated that Atlantic salmon liver microsomes can be stored for 2 years at -80 degrees C in 20% glycerol without losing more than 20-40% of its catalytic activity. PMID- 24213731 TI - Insulin-receptor binding in skeletal muscle of trout. AB - Two hundred rainbow trout (Oncorhynchus mykiss) age 0 +, weight range 11.3 - 11.5 g, were distributed randomly in two groups and maintained for five weeks on either 10% dextrin, or 20% dextrin diet. The fish were sampled 3-5 h and 18-20 h after the last feeding and insulin binding to partially purified insulin receptors in white and red skeletal muscles and to liver plasma membranes was assessed. Plasma insulin, plasma glucose, and liver glycogen content were analyzed in the same fish.Fish fed a diet with higher carbohydrate content (HC) had elevated insulin and glucose levels in peripheral blood, but lower liver glycogen contents compared to the fish fed a diet with lower carbohydrate content (LC). No growth retardation was observed in the fish from HC group.Three to five hours after the last feeding, insulin-receptor binding in white skeletal muscles was higher in HC group of fish, mostly because of an increase in number of high affinity binding sites. Eighteen to twenty hours after the last feeding this difference disappeared. In contrast, the specific binding of insulin to the liver plasma membranes appeared to be lower in the HC group of fish. The lower insulin binding to the liver plasma membranes observed 3-5 h after feeding, could be attributed to the lower quantity of binding sites, while the same phenomenon 18 h after feeding was likely a result of affinity changes. We conclude that higher glycemic levels observed in trout fed a HC diet as compared to LC group of fish, are not a consequence of impaired binding of insulin to its receptors in skeletal muscles. PMID- 24213732 TI - Purification and characterization of hepatic triacylglycerol lipase isolated from rainbow trout,Oncorhynchus mykiss. AB - Trialcylglycerol (TG) lipase was isolated and partially purified from rainbow trout liver. Triacylglycerol lipase activity was assayed by measuring(14)C-oleic acid release from(14)C-triolein.(14)C-oleic acid release was linear for up to two hours. Optimal activity occurred at pH 7.0 and 15 degrees C. Most of the lipase activity was recovered in the cytosolic fraction. A 27,000-fold purification was achieved after Sepharose (Bio-gel A 0.5 M, 200-400 mesh) chromatography of a resuspended 20% ammonium sulfate fraction. The molecular weight of the trout hepatic lipase as determined by size-exclusion chromatography and by SDS polyacrylamide gel electrophoresis was 40-43 kD. Lipase-mediated hydrolysis of TG resulted in the production of diacylglycerols, monoacylglycerols, and fatty acids. Kinetic analysis indicated that Vmax=0.016 nmol/h/mg protein and that Km=0.28 mM triolein. Lipolytic activity was enhanced in the presence of cAMP/ATP Mg(2+). These results suggest that the liver of trout possesses a neutral TG lipase that is responsible for mobilizing stored TG and is catalytically activated by phosphorylation. PMID- 24213734 TI - Malnutrition is associated with poor rehabilitation outcome in elderly inpatients with hospital-associated deconditioning a prospective cohort study. AB - OBJECTIVE: To investigate the association between nutritional status and rehabilitation outcome in elderly inpatients with hospital-associated deconditioning. DESIGN: A prospective cohort study. SUBJECTS/PATIENTS: One hundred sixty-nine consecutive elderly inpatients diagnosed with hospital associated deconditioning. METHODS: Nutritional status at referral was assessed by the Mini Nutritional Assessment Short Form at the University Medical Center. Body mass index, haemoglobin, albumin, total lymphocyte count, C-reactive protein, cause of malnutrition, and feeding route were also investigated. Primary outcome was Barthel Index score at discharge. RESULTS: A total of 148 patients (87.6%) were malnourished, and 21 were at risk for malnutrition. There were no patients with normal nutritional status. Malnourished patients had a lower Barthel Index score at discharge than those at risk for malnutrition. Chronic disease-related malnutrition, oral intake, and parenteral nutrition were associated with the Barthel Index score at discharge. There were significant correlations between the Barthel Index score at discharge and nutritional score, albumin, and total lymphocyte count. In multiple regression analysis, Mini Nutritional Assessment Short Form, albumin, and chronic disease-related malnutrition were significantly associated with the Barthel Index score at discharge. CONCLUSION: Most elderly inpatients with hospital-associated deconditioning are malnourished. Nutritional status, albumin, and chronic disease related malnutrition are associated with poor rehabilitation outcome in hospital associated deconditioning. PMID- 24213733 TI - Glutathione S-transferase in intestine, liver and hepatic lesions of mummichog (Fundulus heteroclitus) from a creosote-contaminated environment. AB - Cytosolic glutathione S-transferase (GSH transferase) activity towards 1-chloro 2,4-dinitrobenzene (CDNB) was elevated approximately three to four-fold in intestine and liver of mummichog (Fundulus heteroclitus) collected from a creosote-contaminated site in the Elizabeth River, Virginia. Intestinal GSH transferase activity at the most heavily contaminated site, at a moderately contaminated site and at a relatively clean site averaged 3.64, 2.83 and 1.11umoles/min/mg respectively, while values for liver at these sites averaged 2.84, 1.75 and 0.93umoles/min/mg. In addition, densitometric tracings of sodium dodecylsulfate-polyacrylamide gels of intestine and liver cytosol revealed a similar trend in the staining intensity of a 25.8 kD protein band, which lies within the molecular weight range of GSH transferase subunits. Activity in putative preneoplastic and neoplastic hepatic lesions of fish collected from the creosote-contaminated site was not significantly different from that of adjacent normal tissue. In the laboratory, dietary betanaphthoflavone (betaNF) treatment resulted in a three-fold increase in intestinal GSH transferase. Hepatic GSH transferase activity in the same fish was not affected by dietary betaNF although hepatic monooxygenase activity, measured as ethoxyresorufin O-deethylase (EROD), was. The results of this study indicate a response of the intestinal detoxification system to environmental contaminants and supports previous studies on the importance of intestinal metabolism of foreign compounds. Further, our results indicate the trend towards elevated GSH transferase in liver of feral fish could not be attributed to a cancerous disease state in these fish but indicates chemical induction in this organ as well. PMID- 24213735 TI - UKA closely preserves natural knee kinematics in vitro. AB - PURPOSE: It is assumed that unicondylar knee arthroplasty (UKA) features kinematics close to the natural knee. Clinical studies have also shown functional benefits for UKA. There is to date only little biomechanical data to support or explain these findings. The purpose of this study was to investigate whether UKA is able to preserve natural knee kinematics or not. METHODS: Six fresh frozen full leg cadaver specimens were prepared to be mounted in a kinematic rig with six degrees of freedom for the knee joint. Three motion patterns were applied before and after medial UKA: passive flexion-extension, open chain extension, and squatting. During the loaded motions, quadriceps and hamstrings muscle forces were applied. Infrared cameras continuously recorded the trajectories of marker frames rigidly attached to femur, tibia, and patella. Prior computer tomography allowed identification of coordinate frames of the bones and calculations of anatomical rotations and translations. RESULTS: Native kinematics was reproduced after UKA in all the specimens. In the unloaded knee and during open chain extension, femoral rollback patterns after UKA were very close to those in the native knee. During squatting, the medial femoral condyle after UKA tended to be more posterior and superior with flexion and there was less tibial internal rotation. The tibia was found to be more in valgus after UKA during all motion patterns. CONCLUSION: As ligaments, lateral compartment and patellofemoral anatomy are preserved with UKA; the unloaded knee closely resembles native kinematics. The slight kinematic changes that were found under load are probably due to loss of the conforming medial meniscus and to the mismatch in geometry and stiffness introduced by UKA. These patterns resemble those found in knees with significant loss of function of the medial meniscus. PMID- 24213736 TI - Arthroscopic repair of bucket-handle tears of the lateral meniscus. AB - PURPOSE: This study was undertaken to document the clinical results of arthroscopic meniscus repair for treatment of displaced bucket-handle tears of the lateral meniscus. METHODS: From 2002 to 2010, 13 patients with symptomatic displaced bucket-handle tears of the lateral meniscus treated by arthroscopic meniscus repair were included in this study. Inclusion criteria were (1) displaced bucket-handle tear of the lateral meniscus demonstrated on magnetic resonance imaging, (2) non-discoid lateral meniscus, (3) stable knee, and (4) tears involving the red-white or red-red zone. Median age at operation was 20 years (range 14-54 years), and the median follow-up period was 4.0 years (range 2 10.7 years). All tears were repaired with either a modified all-inside suture technique only or a combination of the modified all-inside suture and modified outside-in techniques. Clinical results were evaluated preoperatively and at the final follow-up using Tegner activity level, Lysholm knee, and Hospital for Special Surgery (HSS) scores. RESULTS: All patients returned to their prior life activities with little or no limitations, and no reoperations were required during the follow-up period. On the final follow-up, all knees achieved full range of motion, except two knees with limited function during squatting and jumping due to pain. No patient had recurrence of a knee-locking episode. The median Tegner activity level improved significantly from 3 (2-6) to 7 (4-9) (p < 0.0001), mean Lysholm knee score improved from 78.5 +/- 10.7 preoperatively to 94.6 +/- 5.4 (p < 0.0001), and mean preoperative HSS score improved from 80.3 +/- 8.5 to 95.9 +/- 4.2 (p < 0.0001) during the follow-up period. CONCLUSION: Arthroscopic meniscus repair using the modified all-inside suture and modified outside-in techniques showed excellent clinical outcomes for treatment of symptomatic displaced bucket-handle tears of the lateral meniscus and were free of any complications or episodes of recurrence. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 24213738 TI - Photocurrent enhanced dye-sensitized solar cells based on TiO2 loaded K6SiW11O39Co(II)(H2O).xH2O photoanode materials. AB - Through loading of TiO2 on the surface of K6SiW11O39Co(II)(H2O).xH2O (SiW11Co), a novel photoanode material has been created for dye-sensitized solar cells (DSSC). The absorbing band as well as photoelectricity response range of TiO2@SiW11Co is extended to the visible range. In addition, the absorption in the UV range is enhanced notably compared with P25 (raw TiO2). More importantly, the recombination of the TiO2 network is avoided. TiO2@SiW11Co is mixed with P25 powder (wt ~1 : 1) to assemble dye-sensitized (N719) solar cells, which exhibit a short-circuit photocurrent density as high as 18.05 mA cm(-2), which is 64% higher than blank samples under the standard AM1.5G global solar irradiation. In addition, the mechanisms for SiW11Co in DSSC are proposed. PMID- 24213739 TI - Drawing disability in Japanese manga: visual politics, embodied masculinity, and wheelchair basketball in Inoue Takehiko's REAL. AB - This work explores disability in the cultural context of contemporary Japanese comics. In contrast to Western comics, Japanese manga have permeated the social fabric of Japan to the extent that vast numbers of people read manga on a daily basis. It has, in fact, become such a popular medium for visual communication that the Japanese government and education systems utilize manga as a social acculturation and teaching tool. This multibillion dollar industry is incredibly diverse, and one particularly popular genre is sports manga. However, Inoue Takehiko's award-winning manga series REAL departs from more conventional sports manga, which typically focus on able-bodied characters with sometimes exaggerated superhuman physical abilities, by adopting a more realistic approach to the world of wheelchair basketball and the people who play it. At the same time REAL explores cultural attitudes toward disability in Japanese culture-where disability is at times rendered "invisible" either through accessibility problems or lingering associations of disability and shame. It is therefore extremely significant that manga, a visual medium, is rendering disability visible-the ultimate movement from margin to center. REAL devotes considerable attention to realistically illustrating the lived experiences of its characters both on and off the court. Consequently, the series not only educates readers about wheelchair basketball but also provides compelling insight into Japanese cultural notions about masculinity, family, responsibility, and identity. The basketball players-at first marginalized by their disability-join together in the unity of a sport typically characterized by its "abledness." PMID- 24213737 TI - Fetal age estimation using MSCT scans of the mandible. AB - The purpose of this study was to examine a documented fetal collection, to carry out morphometric analysis of femoral length and of the mandible, and to develop diagnostic standards for estimating fetal age at death based on multislice computed tomography (MSCT) reconstructions. The sample was composed of 81 fetuses, whose ages were recorded in weeks of amenorrhea (WA) between 20 to 40 WA. The measurements made were femoral length (FL) and six distances and four angles of the mandible. Femoral length was measured in 81 fetuses (39 females and 42 males). Morphometric study of the mandible was carried out in 65 fetuses (31 females and 34 males), as the mandible was missing in 16 fetuses. R software was used for statistical analyses. Coefficient correlation (R(2)) and linear regression formulas were calculated. Intra-observer and inter-observer variabilities were very satisfactory (intra-class correlation coefficient >=0.95). Our method appears to be reliable and reproducible. Femoral length was most strongly correlated with age (R(2) = 0.9). The measurement of six distances and four mandible angles from four landmark positions showed a correlation similar to the femoral length correlation (R(2) >= 0.72). The results of this study agreed with those of the literature. We conclude that the mandible is a reliable indicator for estimating fetal age at death. Moreover, MSCT has been shown to be an innovative and reliable technology for this purpose. PMID- 24213740 TI - Direct anterior approach to THR: what it is and what it is not. PMID- 24213741 TI - Organochlorine insecticide residues in Ganga river water near Farrukhabad, India. AB - Multiple residues of organochlorine insecticides were monitored in Ganga river water in the district of Farrukhabad in northern Indian for one year (1991-1992). Almost all the samples were found to be contaminated with residues of HCH and DDT. Residues of aldrin, endosulfan and heptachlor were also detected in a larger number of samples. Alpha-HCH, pp'-DDT and alpha-endosulfan were found to dominate over the other isomers of HCH, DDT and endosulfan, respectively. Enhanced percentage of beta-HCH suggests accumulation of this isomer in the aquatic environment. The average concentration of aldrin was more than that of dieldrin. Aldrin residues often exceeded the WHO guideline value for drinking water and the concentration of heptachlor occasionally exceeded the specified limits. PMID- 24213742 TI - Characterizing soils for hazardous waste site assessments. AB - This paper provides a review and justification of the minimum data needed to characterize soils for hazardous waste site assessments and to comply with the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Scientists and managers within the regulatory agency and the liable party need to know what are the important soil characteristics needed to make decisions about risk assessment, what areas need remediation and what remediation options are available. If all parties involved in characterizing a hazardous waste site can agree on the required soils data set prior to starting a site investigation, data can be collected in a more efficient and less costly manner. Having the proper data will aid in reaching decisions on how to address concerns at, and close-out, hazardous waste sites.This paper was prepared to address two specific concerns related to soil characterization for CERCLA remedial response. The first concern is the applicability of traditional soil classification methods to CERCLA soil characterization. The second is the identification of soil characterization data type required for CERCLA risk assessment and analysis of remedial alternatives. These concerns are related, in that the Data Quality Objective (DQO) process addresses both. The DQO process was developed in part to assist CERCLA decision makers in identifying the data types, data quality, and data quantity required to support decisions that must be made during the remedial investigation/feasibility study (RI/FS) process. Data Quality Objectives for Remedial Response Activities: Development Process (US EPA, 1987a) is a guidebook on developing DQOs. This process as it relates to CERCLA soil characterization is discussed in the Data Quality Objective Section of this paper. PMID- 24213743 TI - Framework for designing sampling programs. AB - A general framework for designing sampling programs is described. As part of the sampling program the problem of concern, or reason for sampling, needs to be clearly stated and objectives specified. The development of a conceptual model will assist the clarification of objectives and the choice of indicators to be sampled.Objectives can then be stated as testable hypotheses and decisions made about the samallest difference/changes that are to be detected/observed by the sampling.To allow the collection of representative samples, and the statistical analysis of data to be collected, the potential sources of variability in the data must be considered. Site, selection, frequency and replication must account for the expected variability.Before field collection of samples occurs, the sample collection device needs to be tested as to its efficiency to collect a representative sample. It also will usually be necessary to consider how samples are to be preserved to inhibit biological and chemical change. All sample programs require a quality assurance program to identify, measure and control errors.As well as the above the cost-effectiveness of the program should be evaluated in terms of maximizing the information obtained/cost. PMID- 24213744 TI - Use of chironomid deformities to assess environmental degradation in the Yamaska River, Quebec. AB - The frequency of morphological deformities in chironomid larvae was used to assess environmental degradation at 12 sites in the Yamaska River, Quebec, that were known to be either impacted by agriculture or urban centres, or were relatively clean and used as reference sites. A total of 2273 chironomid larvae were examined for deformities. The overall frequency of deformities at polluted sites was 2.7%, whereas no deformities were observed at the reference sites. The highest incidence of deformities was found downstream of two urban centres, site 9 at Acton Vale (5.1% deformed) and site 12 at Ste Hyacinthe (5.3% deformed). The frequency of deformities at the agricultural sites ranged from 0.8 to 2.5% and was comparable to sites receiving municipal sewage effluent. The occurrence of higher frequencies of deformities downstream of urban centres indicates that the frequency of deformities increases with environmental degradation. PMID- 24213745 TI - Effects of organic amendments and irrigation waters on the physical and chemical properties of two calcareous soils in Bahrain. AB - The present investigation studies the effects of cow and chicken manure and sewage sludge at different rates of addition and with two irrigation waters of different salinities on two major calcareous soils in Bahrain. The aim was to quantify potential improvements in soil quality, the accumulation of trace metals, and quality of leachates.From the pot experiments it was found that soil waterholding capacity did not change significantly after addition of organic amendments, except in the case of sewage sludge. Total organic carbon and total Kjeldhal nitrogen content increased in the 0-5 cm layer. Low salinity water and sewage applications improved aggregate stability. Extractable phosphorus was enhanced by the chicken manure treatment more than others. Addition of different organic amendments did not affect exchangeable cations. pH values did not show appreciable changes and soils were neutral. Trace metals studied were present at non-toxic levels in the 0-5 cm layer. Zinc and copper were the only metal showing a tendency to leach to the lower soil layer. In all cases metal levels in the surface layer were proportional to the quantities added in the amendments and their levels in the leachate were very low. PMID- 24213746 TI - A method for monitoring ground water quality near waste storage facilities. AB - A practical optimization approach developed in this paper derives effective monitoring configurations for detecting contaminants in ground water. The approach integrates numerical simulation of contaminant transport and mathematical programming. Well sites identified by the methodology can be monitored to establish the occurrence of a contaminant release before a plume migrates to a regulatory compliance boundary. Monitoring sites are established along several horizons located between the downgradient margin of a contaminant source and a compliance boundary. A horizon can form an effective line of defense against contaminant migration to the compliance boundary if it is spanned (covered) by a sufficient number of sites to yield a well spacing that is equal to or less than a maximum value established by numerical modeling. The objective function of the integer programming model formulation expresses the goals of: (1) covering a maximum number of siting horizons, and (2) allocating wells to the single most effective horizon. The latter is determined from well spacing requirements and the width of the zone of potential contaminant migration traversed by the horizon. The methodology employs a highly tractable linear programming model formulation, and the user is not required to predefine a set of potential well sites. These attributes can facilitate its implementation in practice. PMID- 24213747 TI - Receptive to replication. PMID- 24213748 TI - Drugs with breakthrough status charm investors. PMID- 24213751 TI - First-in-class anemia drug takes aim at Amgen's dominion. PMID- 24213753 TI - Monoclonal T-cell receptor drugs pique pharma's interest. PMID- 24213755 TI - Anti-infective monoclonals step in where antimicrobials fail. PMID- 24213761 TI - Vaccines for pandemics. PMID- 24213762 TI - In search of dry powder. PMID- 24213763 TI - Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. PMID- 24213764 TI - Reply to Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. PMID- 24213765 TI - Making the biotech IPO work. PMID- 24213766 TI - Health technology assessments and innovation. PMID- 24213767 TI - The biosimilar price is right. PMID- 24213768 TI - Hearing loss and tinnitus--are funders and industry listening? PMID- 24213769 TI - Human genetics as a foundation for innovative drug development. PMID- 24213770 TI - Precompetitive consortia in biomedicine--how are we doing? PMID- 24213771 TI - Patents and China's research and development in agricultural biotechnology. PMID- 24213773 TI - Next-generation sequencing in the clinic. PMID- 24213774 TI - Two views on light sheets. PMID- 24213775 TI - Genetically encoded voltage sensor goes live. PMID- 24213777 TI - So you want to be a computational biologist? PMID- 24213782 TI - Direct organogenesis from internodal segments of in vitro grown shoots of apple cv. Golden delicious. AB - A protocol for direct organogenesis from internodal segments of in vitro grown shoots obtained from mature apple cv. Golden delicious trees is presented. Adventitious buds were initiated on Murashige and Skoog medium (1962) containing various combinations of benzylaminopurine (BAP) and 2,3,5-triiodobenzoic acid (TIBA). Low concentration of BAP (4.4 MUM) in combination with TIBA (1 MUM) gave the best percentage of regeneration. Three repeated cycles of culture and regeneration produced an increase of adventitious budding up to 23%. Although no auxin was used in the organogenic medium, callus was always obtained. The regenerated shoots were micropropagated and rooted. Cytological studies revealed that proliferating buds originated directly from the superficial layers of the internodal explants without an intermediate callus phase. PMID- 24213780 TI - Targeting motivation and self-regulation to increase physical activity among patients with rheumatoid arthritis: a randomised controlled trial. AB - The purpose of this study is to evaluate the effects of targeting both the motivation and action phases of behaviour change in a 5-week intervention to increase physical activity (PA) among patients with rheumatoid arthritis (RA) not meeting current PA recommendations. In a randomised controlled trial, a control group-which received a group-based patient education session led by a physical therapist-was compared to a treatment group which received the education session plus a motivational interview from a physical therapist and two self-regulation coaching sessions from a rheumatology nurse. Outcomes included leisure-time PA, days per week with at least 30 min of moderate-intensity PA, self-efficacy and autonomous motivation (cognitions which predict PA initiation and maintenance), disease activity, functional status, depressive symptoms and fatigue. Effects were assessed using mixed models repeated measures. Of the 78 patients randomised, 76 and 67 completed the post-treatment and follow-up assessments, respectively. Significant treatment effects were found for leisure-time PA (p = 0.022), active days/week (p = 0.016), self-efficacy (p = 0.008) and autonomous motivation (p = 0.001). At post-treatment and 6-months follow-up, significantly more treated patients than controls met current PA recommendations. No significant effects were found for disease activity, functional status, depressive symptoms or fatigue. Combining motivation- and action-focused intervention approaches improved PA-related cognitions and led to improved uptake and maintenance of leisure-time PA. However, further research is necessary to identify ways of helping patients with RA transition to-and maintain-more intensive forms of PA which are more likely to improve disease activity and functional status. PMID- 24213781 TI - WHO-ILAR COPCORD study (stage 1, urban study) in Sanandaj, Iran. AB - This study aims to conduct an urban Community Oriented Program for Control Of Rheumatic Diseases (COPCORD) study in Sanandaj (Kurdistan, Iran). Sanandaj with a population of 311,446 (2006 census), Caucasian of Kurdish subgroup, was selected as the field. Sanandaj was divided into 100 clusters and subjects were randomly selected from them (50 subjects from each cluster). The COPCORD study started on July 2011 and ended on June 2012. Of the households, 1,631 was visited and 5,830 persons were interviewed. The male to female ratio was 0.8-1 (44.5% males, 55.5% females). Musculoskeletal complaints during the past 7 days were detected in 42.8% of the interviewed subjects (36.3% males, 48.1% females). The distribution was 16.7% shoulder, 10% wrist, 9.7% hands and fingers, 7.7% hip, 26.3% knee, 9.9% ankle, 6.4% toes, 9.5% cervical spine, and 21.5% dorsal and lumbar spine. Degenerative joint diseases were detected in 19.4% of the subjects: 1.8% neck, 18.9% knee, 3.9% hands, and 0.51% hip. Low back pain was detected in 16.5%, sciatica in 1.2%, cervical nerve root pain in 0.24%, and soft tissue rheumatism in 5.5%. Inflammatory disorders were 0.51% rheumatoid arthritis, 0.22% seronegative spondyloarthropathy, 0.10% ankylosing spondylitis, 0.05% systemic lupus erythematosus, and 0.10% Behcet's disease . Fibromyalgia was detected in 0.62% and gout in 0.12% of the studied population. Disability was reported by 28.3%. It was present at the study time in 21.4%. Comparing the four COPCORD studies of Iran, the figures (numbers) obtained by COPCORD Sanandaj are much the same as the COPCORD study in Tehran. Joint complaints were seen less frequently than in the COPCORD urban study of Zahedan and rural study of Tuyserkan. Osteoarthritis was higher than in Tehran, but the same as the two others. Soft tissue rheumatism was rather the same. Rheumatoid arthritis was higher than Tehran and Tuyserkan, but lower than Zahedan. PMID- 24213783 TI - Rescuing abortive inter-EBN potato hybrids through double pollination and embryo culture. AB - Regeneration of inter-EBN hybrids among potato species was achieved using embryo rescue techniques. Tetraploid hybrids between 4x(2EBN) Solanum stoloniferum x 4x(4EBN) S. tuberosum Gp. Andigena as well as diploid hybrids between 2x(1EBN) S. chancayense x 2x(2EBN) S. chacoense were obtained by culturing immature hybrid embryos in nutrient medium. Identification of appropriate embryo developmental stages was critical in developing a suitable protocol for rescuing viable hybrid embryos. The use of IVP clones as the second pollinator in 4x(2EBN) x 4x(4EBN) crosses reduced premature fruit drop and helped to identify triploid hybrids. Morphological and cytological examination confirmed true hybridity for a few of the regenerated plants. Male sterility and meiotic abnormalities were characteristic of the hybrids. Several S. stoloniferum-Andigena hybrids were successfully backcrossed to Gp. Andigena. PMID- 24213784 TI - Optimizing the production of transformed pea (Pisum sativum L.) callus using disarmed Agrobacterium tumefaciens strains. AB - For optimization of the transformation procedure with Pisum sativum L. stern explant callus was used to test the effect of disarmed Agrobacterium tumefaciens strains, cocultivation procedures (preconditioning of explants; use of Nicotiana tabacum L. nurse cultures), duration of cocultivation (2, 3 or 4 days), and agents for selection (kanamycin or hygromycin). The succinamopine strain EHA101(pBI1042) produced the highest percentage of transformed calli (77%) when used in conjunction with tobacco nurse culture during four days of cocultivation. Using this strain, kanamycin (76%) and hygromycin (77%) were equally effective selective agents, but for strain LBA4404(pBI1042) percentage of transformed calli was higher for hygromycin (63%) than for kanamycin (17%). The procedures and strains shown to be optimal for transformation of pea callus will now be complemented by a pea regeneration system. PMID- 24213785 TI - Verbascoside production by plant cell cultures. AB - Verbascoside was found to be produced in all calli derived from eleven species that contained the compound in their leaves. Cell suspension cultures were also established in three species, i.e., Leucosceptrum japonicum f. barbinerve, Syringa josikaea, and Sy. vulgaris, all of which were found to produce verbascoside at more than 1 g/l. Of the three species, suspension cultures of L. japonicum f. barbinerve showed rapid growth and the highest yield of verbascoside (1.89 g/l). In these cultures, the effects of major salt concentration in B5 medium on cell growth and verbascoside production were examined. Maximum cell growth and maximum verbascoside production were both achieved by reducing the major salt concentration to half that of the original medium. PMID- 24213786 TI - Optimum tissue culture conditions for selection of resistance to Phytophtora cinnamomi in pine callus tissue. AB - The present experimentation compared the best nutrient medium, temperature, and growth hormones for callus induction and growth of various pine species from different seed sources with their effect on growth of Phytophthora cinnamomi. Callus tissues maintained on a modified Murashige and Skoog medium with 10(-5)M 2,4-D at 26 degrees C in the dark optimized the expression of differential resistance when inoculated with hyphae of P. cinnamomi. High concentration of 2,4 D (5*10(-5)M) inhibited growth of P. cinnamomi. PMID- 24213787 TI - Loss of microtubular orientation and impaired development of prophase bands upon inhibition of RNA synthesis in root meristem cells. AB - Synchronous cells in Allium cepa L. root meristems were treated with 3'deoxyadenosine (cordycepin, an inhibitor of RNA synthesis) when roughly half of the population had reached G2 phase (fast cells) while the other half was still in late S (slow cells). Since this drug also blocks DNA replication, slow cells remained in S while the treatment was continued.Indirect immunodetection of tubulin showed that a band typical of prophase formed in some cells with a portion of their nuclear DNA unreplicated. Most of the cells arrested in late S which had not developed a prophase band had a diminished number of cortical microtubules. Changes in their orientation (from transversal to oblique or longitudinal) occurred in roughly a cycle time (28 h).In the presence of 3'deoxyadenosine, fast cells which had reached G2 at the start of the treatment proceeded to prophase and remained there. Mature prophase bands were also formed in these cells but eventually they disoriented and, finally, disappeared. The data suggest that microtubular orientation in the meristematic cells depends on long-lived RNA species. PMID- 24213788 TI - Effect of carbon dioxide and ethylene on berberine production and cell browning in Thalictrum minus cell cultures. AB - Cultured cells of Thalictrum minus L. (Ranunculaceae), transferred from culture flasks to a bubble column bioreactor, produced little berberine and turned dark brown, even when supplied with sufficient oxygen. This phenomenon was ascribed to the removal of CO2 from the culture medium by bubbling air, and could be reproduced in flask cultures artificially deprived of CO2. The induction of cell browning by exogenously administered ethylene suggested that CO2 probably acts antagonistically against endogenously generated C2H4. The physiological damage caused by forced aeration could be prevented by adding 2 % CO2 to the air in the bioreactor. PMID- 24213789 TI - Effects of low nitrate and high sugar concentrations on anthocyanin content and composition of grape (Vitis vinifera L.) cell suspension. AB - In pigmented cells of Vitis vinifera suspension cultures, best accumulation of anthocyanins was obtained when nitrate concentration was reduced from 25 mM to 6.25 mM and when sucrose concentration was increased from 88 mM to 132 mM. Under such conditions growth was greatly decreased. However, cell viability was maintained. The increases in anthocyanins in pigmented cells were due largely to increases in peonidin - glucoside. The high sucrose and the low nitrate concentrations can be one of the important culture factors in controlling of anthocyanin production by cell cultures. PMID- 24213790 TI - Genetic transformation of Chrysanthemum using wild type Agrobacterium strains; strain and cultivar specificity. AB - To develop an Agrobacterium mediated transformation protocol for chrysanthemum we studied the transformation efficiency of commonly used A.tumefaciens strains on 14 genotypes by comparing tumour size and frequency. One genotype was analyzed in detail using 14 strains of both A.tumefaciens and A.rhizogenes. Only a few genotype/strain combinations resulted in significant tumour formation. Especially 0-type strains were highly efficient. An 0-type strain was used to transfer genes for neomycine phosphotransferase (NPT II) and beta-glucuronidase (GUS) to a susceptible cultivar. Transfer of the GUS gene was confirmed by using the Polymerase Chain Reaction (PCR). PMID- 24213791 TI - Cytokinin induced somatic embryogenesis from immature embryos of Abies nordmanniana Lk. AB - Abies nordmanniana Lk. is used in short intensive rotations for Christmas tree production. Thus there is a high demand for development of advanced propagation and breeding methods. Somatic embryogenesis was easily induced from immature (precotyledonary) embryos collected in July 1989 with cytokinin as the sole plant growth regulator. The proliferating embryogenic cell masses were characteristic of conifer somatic embryogenesis and could be maintained on a simple basal medium containing 5 MUM benzylaminopurine. Auxin inhibited induction as well as proliferation. Proliferation was improved by up to 30 % by addition of L glutamine and/or casein hydrolysate. Neither cytokinin concentration nor culture on 3 different basal media, differing markedly in their nitrogen composition, affected the proliferation rate. Embryos matured using a 4 week subculture on medium containing 10 MUM abscisic acid and subsequent transfer to medium devoid of plant growth regulators. PMID- 24213792 TI - Somatic embryogenesis and plant regeneration in Acanthopanax senticosus. AB - Mature embryos of Acanthopanax senticosus explanted on Murashige and Skoog (MS) medium with 0.5 mg/1 2,4-D developed somatic embryos directly from swollen cotyledon and embryo axes within one to two months. When the somatic embryos were transferred to medium supplemented with 2,4-D (0.5 mg/1) or IAA (1-3 mg/1) or Zeatin (0.5 mg/1) and NAA (0.2 mg/1), additional somatic embryos developed. Most (93%) embryos germinated on the above medium without 2,4-D. Sixty-two percent of the plantlets survived in soil. Histological observations revealed that the somatic embryos originated from cell masses of epidermal and sub-epidermal origin. There was no cytological separation zone between the somatic embryos and cultured expiants. Consequently, embryos were difficult to separate from their expiant tissue. PMID- 24213793 TI - Vitreous state in vitro culture: ethylene versus cytokinin. AB - The occurrence of a developmental anomaly i in vitro culture, named "vitreous plant", has been shown to be a deficiency in lignification. Several causes have been proposed, most recently the physical state of the culture medium and ethylene. Experiments, conducted to verify these suggestions, led toresults that did not confirm either the physical state or ethylene as causal agents. It rather appeared that cytokinins did induce the anomaly, probably by excessively promoting cell-divisions at the expense of cell-differentiation. PMID- 24213794 TI - Plant regeneration from protoplasts of Solanum species with potential agricultural value (S. hjertingii, S. polyadenium, S. capsicibaccatum). AB - Protoplasts have been isolated from three tuber-bearing Solanum species, S. hjertingii, S. polyadenium and S. capsicibaccatum, that are sexually incompatible with S. tuberosum, but possess potentially useful characters. For isolating protoplasts from leaves of in vitro shoot cultures of S. hjertingii and S. capsicibaccatum growth was improved by including silver thiosulfate in the medium. However, for S. polyadenium, leaves of pot-grown plants were the best source for protoplasts. Following protoplast division and culture, plants were regenerated from protoplasts of each of the species. The pattern of chromosome variation in regenerants was similar to that observed for other diploid and tetraploid Solanum species. The results indicate that it should be possible to introduce the potentially useful germplasm from these wild species into somatic hybrids with S. tuberosum by protoplast fusion. PMID- 24213795 TI - Plant regeneration from callus cultures of Valeriana wallichii DC. AB - Petiole expiants of Valeriana wallichii. DC., a threatened medicinal plant, were used for inducing callus. Optimum callus formation was observed on Murashige and Skoogs' (1962) medium supplemented with 3.0 mg/l NAA and 0.25 mg/l Kn. Shoot regeneration was achieved upon transferring the callus to medium containing 1.0 mg/l Kn and 0.25 mg/l NAA. Complete plantlets were obtained on the same medium or upon transfer of the regenerated shoot buds to medium containing 5.0 mg/l Kn and 1.0 mg/l IAA. Nearly a thousand callus regenerated plants were successfully transferred to the field following previously standardized hardening procedures. PMID- 24213796 TI - Intra- and extracellular carbohydrates in plant cell cultures investigated by (1)H-NMR. AB - With the aim of quantifying intra- and extracellular carbohydrates media and cell extracts from a Tabernaemontana divaricata plant cell-suspension culture were investigated with (1)H-NMR.For suppression of the solvent peak the Meiboom-Gill modification of the Carr-Purcell (CPMG) spin-echo sequence was used after addition of a paramagnetic relaxation agent (Mn(2+)) to the sample. Several aspects of this method were optimized (the manganese concentration, the interpulse delay and the number of spin-echo cycles) so as to obtain a rapid and easy method in which no pretreatment of media or cell-extracts was needed. Besides the speed and ease of the method, also the direct identification of carbohydrates and other main components is an advantage.The exhaustion of extracellular carbohydrates was found to coincide with the maximum amount of intracellular carbohydrates. The intracellular carbohydrates, i.e. glucose and fructose, were consumed at a low rate, during several weeks. PMID- 24213797 TI - Emetine enhances the tumor necrosis factor-related apoptosis-inducing ligand induced apoptosis of pancreatic cancer cells by downregulation of myeloid cell leukemia sequence-1 protein. AB - Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent, it shows limited efficacy in human pancreatic cancer cells. Protein synthesis inhibition has been reported to sensitize cancer cells to apoptosis-inducing agents, but the detailed mechanism by which protein synthesis inhibition sensitize cells to TRAIL has not been determined. To investigate the mechanism underlying pancreatic cancer cell resistance to TRAIL, we performed a small scale high-throughput compound screening in AsPC-1 pancreatic cancer cells using a bioactive small molecule library. We identified 8 compounds that reproducibly sensitize AsPC-1 cells to TRAIL-induced apoptosis. One of these compounds, emetine hydrochloride, when combined with subtoxic concentrations of TRAIL, induced massive apoptosis in AsPC-1 and BxPC-3 pancreatic cancer cells. Cell death analysis revealed that the sensitizing effects of emetine were specific to TRAIL. Emetine downregulated the expression of the TRAIL-related anti-apoptotic protein Mcl-1 in a dose- and time-dependent manner. Furthermore, specific knockdown of Mcl-1 using small interfering RNA without emetine treatment sensitized pancreatic cancer cells to TRAIL. Emetine sensitization of pancreatic cancer cells to TRAIL via Mcl-1 was confirmed under hypoxic conditions. Taken together, these findings strongly suggest that Mcl-1 is involved in pancreatic cancer cell resistance to TRAIL, and emetine facilitates the apoptosis of TRAIL-tolerant pancreatic cancer cells by specifically inhibiting Mcl-1 function. PMID- 24213798 TI - The arsenic content of bottled mineral waters. AB - The arsenic levels of 23 mineral waters on sale to the public in the United Kingdom were measured. The arsenic content of most waters was below 1 MUg L(-1) but the statutory limits of 50 ug L(-1) for natural mineral waters and 100 MUg L( 1) for non-alcoholic beverages were exceeded by the French mineral water, Vichy Celestins (220 ug L(-1)). Regular consumption of mineral water of such elevated concentration could make a significant contribution to the intake of the more toxic inorganic species of arsenic, with possible adverse long-term effects on the health of some individuals. The general need for analytical speciation studies of dietary arsenic is emphasised. PMID- 24213799 TI - Histological demonstration of immunoreactive metallothionein in sections of human and rat tissue. AB - Immunoreactive metallothionein has been demonstrated in formalin fixed sections of rat and human tissue using a DNP hapten sandwich staining procedure and antibody to zinc-induced rat liver metallothionein II.MT was found in rat liver, duodenum, jejunum and ileum and in human liver and ileum both intracellularly in hepatocytes and enterocytes and extracellularly in portal vessels, sinusoids and canaliculi in the liver and in the lamina propria of the intestine.Changes in intensity of staining were related in the rat to the feeding/fasting status of the animal and whether exogenous zinc had been administered. In man least MT was found in the ileum of patients with Crohn's disease and most in patients with non inflammatory bowel disease.These results confirm that MT is an important physiological metal-binding protein in man and animals and is concerned in zinc transport and binding in rats. PMID- 24213800 TI - Arsenic in garden soils and vegetable crops in Cornwall, England: Implications for human health. AB - Total concentrations of arsenic in surface (0-15cm) garden soils in the historical mining area of Hayle-Camborne-Godolphin, Cornwall, England are large and range widely (144-892 MUg/g). Amounts of water soluble and acid-fluoride extractable soil arsenic are significantly correlated with total content.Examination of 6 salad and vegetable crops grown in 32 gardens has shown arsenic concentrations in the edible tissues to be only slightly elevated. There were strong correlations between arsenic in beetroot, lettuce, onion and peas and soil arsenic (total, water soluble and acid extractable). Regression equations have been calculated. Ridge regression analysis applied to test the importance of other soil variables has shown both iron and phosphorus to influence the uptake of arsenic.Arsenic in all the vegetables sampled was below the statutory limit in the U.K. of 1 mg/kg fresh weight. Implications for health should be assessed in relation to other exposure routesvia water, air and directly ingested dust and soil. PMID- 24213801 TI - Predicting water quality data in an unfilled reservoir using microcosm sediment water simulation. AB - The technique of microcosm sediment-water simulation was used to obtain predictive water quality data for the proposed Jordanelle Reservoir, Heber City, Utah. Sediment-water microcosms were prepared for four sites located in the north arm of the reservoir basin, including two sites located in an abandoned acid mine tailings pond. Data obtained from the tailings pond microcosms indicated that low pH water and high trace metal concentrations may exist in this area of the reservoir. These data suggested that the tailings material should be contained or removed prior to reservoir filling. Other sites in the reservoir basin exhibited water quality considered normal for reservoirs of similar elevation and basin geology. Near the proposed dam, anaerobic conditions could develop rapidly due to available concentrations of organic carbon, and the subsequent release of Zn, Fe, and Mn may pose a water quality problem. At the sampling site near Keetley, simulation data indicated that anaerobic conditions will not develop as quickly or be as severe as conditions expected near the dam. Overall, the availability of nitrogen and phosphorus in the Provo River and Jordanelle sediments indicated that problems with algal blooms may exist in the reservoir. Also presented is a brief discussion of the advantages and disadvantages associated with microcosm sediment-water simulation. PMID- 24213802 TI - Native legume establishment on acidic coal mining overburden at Collie, Western Australia. AB - Nitrogen is often provided to impoverished overburden dumps through the establishment of legumes. Low indigenous soil nutrient levels, summer drought conditions and an acidic mining overburden represent major obstacles to successful rehabilitation of open-cut coal mining at Collie in southwest Western Australia. In this study,Acacia pulchella, a native Western Australian species often used in rehabilitation of mined lands, was shown to nodulate and grow in coal mining overburden with pH values less than 4.0 under glasshouse conditions. Plant growth (both top and root dry weight), nodule fresh weight, and nodulation success was best at a pH near 5.0, a value only slightly lower than the typical soil pH of the native jarrah (Eucalyptus marginata) forest. Acetylene reduction rates were reduced by acidity and ranged from 8.2 MUm C2H4g(-1)hr(-1) at pH 6.77 to 3.0 MUm C2H4g(-1)hr(-1) at a pH of 3.98. Four additional plant species were found to occur and to nodulate on acid overburden material at Collie. PMID- 24213803 TI - Airs, waters and places. PMID- 24213804 TI - Guest editorial. PMID- 24213805 TI - Penetration and lateral diffusion characteristics of polycrystalline graphene barriers. AB - We report penetration and lateral diffusion behavior of environmental molecules on synthesized polycrystalline graphene. Penetration occurs through graphene grain boundaries resulting in local oxidation. However, when the penetrated molecules diffuse laterally, the oxidation region will expand. Therefore, we measured the lateral diffusion rate along the graphene-copper interface for the first time by the environment-assisted crack growth test. It is clearly shown that the lateral diffusion is suppressed due to the high van der Waals interaction. Finally, we employed bilayer graphene for a perfect diffusion barrier facilitated by decreased defect density and increased lateral diffusion path. PMID- 24213806 TI - Quantitative comparison of dynamic physiological feeding profiles for recombinant protein production with Pichia pastoris. AB - Pichia pastoris is widely used for the production of recombinant proteins in industrial biotechnology. In general, industrial production processes describe fed-batch processes based on the specific growth rate. Recently, we introduced the specific substrate uptake rate (q s) as a novel parameter to design fed-batch strategies for P. pastoris. We showed that a dynamic feeding strategy where the feed was adjusted in steps to the maximum specific substrate uptake rate was superior to more traditional strategies in terms of specific productivity. In the present study, we compare three different dynamic feeding strategies based on q s for a recombinant P. pastoris strain with respect to cell physiology, methanol accumulation, productivity and product quality. By comparing (A) a feeding profile at constant high q s, (B) a periodically adjusted feeding profile for a stepwise q s ramp, and (C) a feeding profile at linear increasing q s, we evaluated potential effects of the mode of feeding. Although a dynamic feeding strategy with stepwise increases of q s to q s max resulted in the highest specific productivity, a feeding profile where the feeding rate was stepwise increased to a constant high q s value was superior in terms of the amount of active enzyme produced and in the amount of accumulated methanol. Furthermore, this feeding strategy could be run automatically by integrating an online calculator tool, thus rendering manual interventions by the operator unnecessary. PMID- 24213807 TI - SIRT6, a protein with many faces. AB - Sirtuins are NAD(+) dependent deacylases enzymes. There are seven mammalian sirtuins, SIRT1-SIRT7, which are localized to different cellular compartments and are capable of diverse catalytic activities. SIRT6 is a key regulator of healthy ageing. In the past decade our understanding of SIRT6 significantly increased in many different aspects. We know its cellular localization, catalytic activities, substrates and the pathways it is involved in. This review discusses the recent discoveries regarding the SIRT6 enzyme. PMID- 24213808 TI - Hypercholesterolemia abrogates the cardioprotection of ischemic postconditioning in isolated rat heart: roles of glycogen synthase kinase-3beta and the mitochondrial permeability transition pore. AB - Ischemic postconditioning (IPO) reduces lethal reperfusion injury under normal conditions, but its effectiveness in hypercholesterolemia (HC) is disputed. We measured the cardioprotection of IPO in hypercholesterolemic rats and determined the roles of glycogen synthase kinase-3beta (GSK-3beta) and the mitochondrial permeability transition pore (mPTP). Isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Postconditioning protocol induced six cycles of 10s ischemia and 10s reperfusion at the onset of the reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride staining and cardiomyocyte apoptosis was assessed by TUNEL staining. GSK-3beta phosphorylation was measured by immunoblotting. The opening of mPTP was measured by NAD(+) content in myocardium. In normocholesterolemia (NC) groups, infarct size and cardiomyocyte apoptosis were significantly reduced after IPO. These reductions were completely abolished by HC, as evidenced by a similar infarct size and cardiomyocyte apoptosis observed between the IPO-HC and IR (ischemia-reperfusion) HC groups. GSK-3beta phosphorylation was significantly higher in the IPO-NC than the IPO-HC group. In addition, NAD(+) content in myocardium, a marker of mPTP opening, was higher in the IPO-NC group than the IPO-HC group. In conclusion, cardioprotection of IPO is blocked by hypercholesterolemia. This might be due to the impairment of phosphorylation of GSK-3beta and attenuation of mPTP opening. PMID- 24213809 TI - Deciphering the role of Burkholderia cenocepacia membrane proteins in antimicrobial properties of chitosan. AB - Chitosan, a versatile derivative of chitin, is widely used as an antimicrobial agent either alone or mixed with other natural polymers. Burkholderia cenocepacia is a multidrug-resistant bacteria and difficult to eradicate. Our previous studies shown that chitosan had strong antibacterial activity against B. cenocepacia. In the current study, we have investigated the molecular aspects for the susceptibility of B. cenocepacia in response to chitosan antibacterial activity. We have conducted RNA expression analysis of drug efflux system by RT PCR, membrane protein profiling by SDS-PAGE, and by LC-MS/MS analysis following the validation of selected membrane proteins by real-time PCR analysis. By RT-PCR analysis, it was found that orf3, orf9, and orf13 were expressed at detectable levels, which were similar to control, while rest of the orf did not express. Moreover, shotgun proteomics analysis revealed 21 proteins in chitosan-treated cells and 16 proteins in control. Among them 4 proteins were detected as shared proteins under control and chitosan-treated cells and 17 proteins as uniquely identified proteins under chitosan-treated cells. Among the catalog of uniquely identified proteins, there were proteins involved in electron transport chain and ATP synthase, metabolism of carbohydrates and adaptation to atypical conditions proteins which indicate that utilization and pattern of chitosan is diverse which might be responsible for its antibacterial effects on bacteria. Moreover, our results showed that RND drug efflux system, which display the ability to transport a variety of structurally unrelated drugs from a cell and consequently are capable of conferring resistance to a diverse range of chemotherapeutic agents, was not determined to play its role in response to chitosan. It might be lipopolysaccharides interaction with chitosan resulted in the destabilization of membrane protein to membrane lyses to cell death. Membrane proteome analysis were also validated by RT-qPCR analysis, which corroborated our results that of membrane proteins. PMID- 24213811 TI - Symmetrical giant facial plaque-type juvenile xanthogranuloma persisting beyond 10 years of age. PMID- 24213810 TI - Craniofacial anatomical risk factors in men with obstructive sleep apnea and heart failure: a pilot study. AB - PURPOSE: Obstructive sleep apnea (OSA) is complicated with heart failure (HF); however, the reason for this is not well understood. Craniofacial anatomic risk factors may contribute to OSA pathogenesis in HF patients. However, there are no data about cephalometric findings among OSA patients with HF. METHODS: Consecutive patients with HF and OSA (defined as total apnea-hypopnea index (AHI) >=15/h) were enrolled. As controls, OSA patients without HF but matching the test group in age, BMI, and obstructive AHI were also enrolled. RESULTS: Overall, 17 OSA patients with HF and 34 OSA patients without HF were compared. There are no significant differences in the characteristics or polysomnographic parameters between 2 groups. In the cephalometric findings, compared with patients without HF, patients with HF showed a significantly greater angle between the line SN to point "A" (SNA) and a longer inferior airway space and greater airway area. However, the tongue area of patients with HF was more than those without HF. CONCLUSIONS: The craniofacial structures of OSA patients with HF were different from those without HF. OSA patients with HF had an upper airway anatomy that is more likely to collapse when sleeping while recumbent, despite having a larger airway space. PMID- 24213812 TI - Unique Y-shaped lanthanide aggregates and single-molecule magnet behaviour for the Dy4 analogue. AB - The assembly of N'-(amino-(pyrimidin-2-yl)methylene)-o-vanilloyl hydrazine ligands (H2L, Scheme 1) with different lanthanide perchlorates produces novel Y shaped tetranuclear complexes, [Ln4(MU3-OH)(L(2-))4(H2O)6].(ClO4)3.6H2O, where Ln = Tb (1), Dy (2) and Ho (3). The formation of this unprecedented Y-shaped topology is largely ascribed to the versatility of the mixed-donor hydrazone ligands in terms of their potential denticity. Analysis of the susceptibility data shows that only the Dy-based molecule features SMM-like behaviour. The synthetic methodology of employing H2L and related ligands has provided a very promising route towards new families of magnetic coordination clusters with novel metal topologies and properties. PMID- 24213813 TI - Computational study of diastereoselective ortho-lithiations of chiral ferrocenes. AB - Diastereoselective ortho-lithiations serve for the preparation of many important chiral ferrocenes, however diastereoselections of these lithiations are explained only by simple steric models. We elucidated ortho-lithiations of three important ferrocenes based on DFT calculations. The calculations showed that simple models of transition states involving ferrocenyl substrates and lithium bases can only in some cases account for the experimental results. Transition state models, which include solvent or coordinating additives as distinct entities bound to lithium, can satisfactorily explain diastereoselection of the ortho-lithiations of chiral ferrocenes. PMID- 24213814 TI - Nitrogenous waste excretion and accumulation of urea and ammonia inChalcalburnus tarichi (Cyprinidae), endemic to the extremely alkaline Lake Van (Eastern Turkey). AB - The endemic, anadromous cyprinidChalcalburnus tarichi is the only fish species known to occur in alkaline Lake Van (Eastern Anatolia, Turkey). EightC. tarichi were maintained individually in Lake Van water (17 - 19 degrees C; pH 9.8; 153 mEq.I(-1) total alkalinity; 220/00 total salinity) and tank water samples analyzed for 24 h in 2 to 4 h intervals. At zero time, < 1uM ammonia was present and urea was undetectable in the tank water; at 24 h, total ammonia and urea made up 114+/-32 and 35+/-25uM, respectively. Over the experimental period, ammonia-N and urea-N excretion averaged 1041+/-494 and 607+/-169MUmoles.kg(-1) fish.h(-1), respectively. The extent of urea excretion was highly variable between specimens. Uric acid excretion was not detectable.Urea was present at high concentrations in all tissues and plasma (25 - 35MUmoles.g(-1).ml(-1)) of freshly caughtC. tarichi; total ammonia content of the tissues was by a factor of 1.9 (liver) to 3.0 (brain) lower. High arginase activity (2.4+/-0.2 U.min(-1).g(-1)) was detected in the liver ofC. tarichi but ornithine carbamoylphosphate transferase, a key enzyme of the ornithine-urea-cycle, was absent. Ureagenesis is likely through degradation of arginine and/or uricolysis. High glutamine synthetase activity (11+/-0.6 U.min(-1).g(-1)) and low ammonia content in brain suggest that, like other teleosts,C. tarichi has an efficient ammonia detoxification in the brain, but in no other tissue.Nitrogenous waste excretion at alkaline pH is discussed. The ability ofC. tarichi to excrete high levels of ammonia at extremely alkaline pH is unique among teleosts studied so far. The mechanism of ammonia excretion under Lake Van conditions remains to be elucidated. PMID- 24213815 TI - The effect of water-borne magnesium on the dietary magnesium requirement of the rainbow trout (Oncorhynchus mykiss). AB - Rainbow trout (Oncorhynchus mykiss) (mean initial weight 0.84 g) were fed diets containing graded levels of magnesium (Mg) (78 to 725ug/g) while being exposed to one of several levels in the rearing water (1.4 to 1000 mg/l). Uptake of Mg from the water, in Mg-deficient fish, was linearly related to the water Mg concentrated. It appears that the fish's Mg requirement can be met from either or both the diet or water. Under the experimental conditions, a water-borne concentration of 46 mg/l was calculated to be sufficient to meet the Mg requirement of the fish fed a Mg-free diet. PMID- 24213816 TI - Lipids of arctic charr,Salvelinus alpinus (L.) II. Influence of dietary fatty acids on the elongation and desaturation of linoleic and linolenic acid. AB - Arctic charr,Salvelinus alpinus L. were fed five test diets containing 0% or 1% of different polyunsaturated fatty acids (PUFA) for 93 days. The fish were injected intraperitoneally with (1-(14)C)-18:2(n-6) or (1-(14)C)-18:3(n-3), and the bioconversion to longer chain PUFA studied. The conversion rate in neutral lipids was slow, with most label found as the fatty acid injected, while extensive modification took place prior to or during incorporation into polar lipids. Linolenic acid was preferred over linoleic acid as substrate for elongation and desaturation regardless of diet. In polar lipids, the predominant products of (1-(14)C)-18:2(n-6) metabolism were generally 20:3(n-6) and 20:4(n 6), while 18:4(n-3), 20:5(n-3) and 22:6(n-3) were the major products of (1-(14)C) 18:3(n-3) metabolism. The lack of radioactivity in 22:5(n-6) suggests that Delta 4 desaturation is specific for (n-3) PUFA. Feeding the PUFA deficient diet reduced the Delta 5 desaturation compared to fish maintained on PUFA supplemented diets. The Delta 6 desaturation was only reduced in fish fed C18 PUFA and injected with (1-(14)C)-18:3(n-3). Longer chain C20 and C22 PUFA, particularly those of the (n-3) family, exerted some inhibition on the elongation and desaturation of injected fatty acids compared to those fed C18 PUFA. The incorporation of radiolabelled fatty acids into polar lipids of fish fed a commercial diet was very low, and the desaturation neglectible in both polar and neutral lipids, showing that Arctic charr under culture conditions do not convert short chain PUFA to longer chain metabolites. PMID- 24213817 TI - The essential fatty acid requirement of milkfish (Chanos chanos Forsskal). AB - The essential fatty acid (EFA) requirement of milkfish was examined by a 12-week feeding trial using defined, purified diets at water temperature of 28-29 degrees C and salinity of 320/00. The test diets contained varying levels of 18:0 (triglyceride form, TG), 18:3(n-3), 18:2(n-6) and (n-3) highly unsaturated fatty acids (n-3 HUFA). Milkfish juveniles were starved for 7 days and were than fed lipid-free diet for 30 days before the initiation of feeding trials. Low growth and feed efficiency together with high mortalities were observed in fish fed the lipid-free diet as well as in the EFA-deficient diet. Supplementation of 2% 18:2(n-6) to the tristearin based diet did not improve growth rate of milkfish as effectively as feeding with (n-3) fatty acids. The highest weight gain was obtained in milkfish fed a combination of 5% 18:0 + 1.0% 18:3(n-3) + 0.5% 20:5(n 3) + 0.5% 22:6(n-3) although the supplementation of 2% 18:3(n-3) alone or combination of 0.5% 20:5(n-3) + 0.5% 22:6(n-3) to the tristearin based diets were also effective for improvement of growth. Thus, (n-3) fatty acids, such as 18:3(n 3) and (n-3)HUFA were nutritionally more important than 18:2(n-6) for milkfish. The fatty acid composition of the polar lipids from whole body of milkfish juveniles fed the various test diets were influenced by the composition of the dietary fatty acids. PMID- 24213818 TI - Summertime and early autumn activity of some enzymes in the carbohydrate and fatty acid metabolism of the crucian carp. AB - In June, July, and September the activities of five enzymes involved in the carbohydrate and fatty acid metabolism, namely phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS), cytochrome oxidase (cyt ox) and 3 hydroxy-acyl-CoA dehydrogenase (HAD), were measured in the heart, liver, red muscle, white muscle, and gill lamellae of crucian carp (Carassius carassius). LDH activity was measured in both reducing (LDHr) and oxidizing (LDHo) directions.The PFK activity in red and white muscle increased significantly between July and September indicating a preparation to winter anoxia by an increased glycylytic capacity in these organs. The HAD activity of the liver had increased significantly (by more than 50%) by September, also a preparation to winter anoxia as HAD is used in the reversed beta-oxidation (chain elongation of fatty acids). The LDHr and cyt ox activities in the heart and white muscle were highest in July. This shows that both the anaerobic and aerobic capacities are elevated in mid-summer when water temperature is high and oxygen concentration of the water could fluctuate greatly. The LDHo and CS activities in gill lamellae were lowest in July. The results show that the metabolism of crucian carp is under seasonal influence and that a preparation to winter hypoxia/anoxia could be detected in September. PMID- 24213819 TI - Quantitative changes in a serum protein, AS, during the life cycle of the lamprey,Petromyzon marinus L. AB - The electrophoretically fastest migrating protein in ammocoete serum, AS protein, was isolated and found to be an acidic glycoprotein with a molecular weight of 140,000 Daltons. Purified AS was injected into rabbits to produce a monospecific antiserum that was used in rocket immunoelectrophoresis to quantitate AS at different periods in the life cycle. AS was found to constitute approximately 70% of total serum protein in the ammocoete, remained at about the same value during transformation, and was reduced to 38% of total serum protein in the juvenile adult. In both male and female upstream migrant animals, AS was less than 0.5% of total serum protein. When juveniles were acclimated to seawater over a 10 week period, it was found that their AS level was reduced by 92% to 3.8% of total serum protein. These results are discussed in relation to changes in other serum proteins at various intervals of the lamprey life cycle. PMID- 24213820 TI - Presence and ontogeny of intestinal and pancreatic phospholipase A2-like proteins in the Red Sea bream,Pagrus major. An immunocytochemical study. AB - We have studied the location and the ontogeny of the digestive enzyme, phospholipase A2 (PLA2) immunohistochemically in the adult and larvae/juvenile of the red sea breamPagrus major by using an antiserum against theNaja naja venom PLA2. The antiserum reacts with at least one enzyme among the PLA2s purified from the fish hepatopancreas or intestine. Although the reactivities were comparatively low, it labelled zymogen granules of the pancreatic acinar cells and secretory materials of certain epithelial cells in the depths of epithelial crypts in the pyloric caeca of the adult. The immunoreactivities of PLA2s were investigated in the viscera of larvae and juveniles of the 0 to 85(th) day after hatch. In the larvae of the 13(th) day, accumulation of PLA2-positive zymogen granules in the pancreatic acinar cells were first recognized by the immunostaining. The intensity of the labelling subsequently became stronger and dramatically increased between the 20(th) and 30(th) day. This increase appeared to be one of the physiological changes associated with the transition to a new benthic life as juveniles. Lack of PLA2 in the pancreas before the 13(th) day may suggest the possibility that larvae utilized exogenous PLA2, inherent in their prey, to digest the phospholipids. On the other hand, no reactivity was found in the intestine until the 85(th) day. PMID- 24213821 TI - Characterization of a pancreatic DNase from pyloric caeca of atlantic cod (Gadus morhua L.). AB - An alkaline deoxyribonuclease (DNase) from cod pancreatic tissue has been characterized. The enzyme is a DNase I type endonuclease and hydrolyzes effectively both native and denatured DNA. Monomeric actin inhibits the enzyme reaction. The enzyme obeys Michaelis-Menten kinetics and the apparent Km value for native linear duplex DNA is 33 ug/ml. The cod DNase opens supercoiled plasmid DNA, by introducing adjacent nicks in both strands, possibly separated by 5-10 nucleotides. DNA hydrolyzed by cod DNase functions as substrates both for DNA polymerase and ligase, and the nicks therefore contain 5'-phosphoryl and 3' hydroxyl groups. Optimum concentrations of divalent cations are 5 mM Mg(2+), 0.63 mM Mn(2+) and 0.075 mM Ca(2+). However, Ca(2+) is apparently not essential for the enzymatic functions. The enzyme has a narrow temperature optimum at 42 degrees C and is thermolabile above 50 degrees C; however, Mn(2+) shifts the optimum slightly to 45 degrees C by causing increased temperature stability. The cod DNase reaction is inhibited by the DNA intercalating compounds actinomycin D and ethidium bromide. Histidine-modifying reagents such as tosyl phenylalanyl chloromethylketone and diethyl pyrocarbonate inhibit the enzyme activity, but the cod DNase is insensitive to disulfide-reducing agents. PMID- 24213822 TI - Metabolism of low density lipoproteins in rainbow trout. AB - Plasma kinetics and tissue sites of degradation for native and chemically modified low density lipoproteins have been investigated in (Oncorhynchus mykiss). Native and modified LDL labelled with(125)I-tyramine-cellobiose, (a residualizing adduct), were injected intravenously, and plasma and organ samples analyzed. Native LDL were cleared with a half life of about 30 hours, and mainly catabolized in the liver. Acetylation of LDL resulted in accelerated clearance (t1/2=2 h) and catabolism in the kidneys. Methylation of LDL had only minor effects on catabolism. The cellular localization of lipoprotein uptake was visualized in kidney by fluorescence microscopy. Native LDL were endocytozed by spheroid, parenchymal cells, supposedly steroid-producing cells. Acetylated, fluorescent LDL were found in vacuoles of flattened, sinusoidal lining endothelial cells. Our data show that catabolism of native low density lipoproteins in salmonids takes place mainly via hepatic receptors. A scavenger receptor pathway, for modified lipoproteins (mainly localized in the kidney) is also operative in trout. PMID- 24213824 TI - Role of thyroid hormones in tilapia larvae (Oreochromis mossambicus): I. Effects of the hormones and an antithyroid drug on yolk absorption, growth and development. AB - Treatment of one-day old yolksac larvae of tilapia (Oreochromis mossambicus) by immersion in 0.05 ppm T4 or 0.01 ppm T3 significantly accelerated the differentiation and growth of all the fins, particularly pectoral and tail fins. Both the treatments also significantly accelerated yolk absorption and transition to free-swimming activity in the larvae. The treatments also significantly accelerated the growth of the larvae, with T3 at 0.01 ppm having a greater effect than T4 at 0.05 ppm. The yolk conversion efficiency was found not to be significantly affected by the hormone treatments but the treated larvae exhibited an increased heart beat, suggesting metabolic stimulation by the hormones.On the other hand, yolk absorption and free-swimming activity were significantly delayed in tilapia larvae immersed in 25 ppm solution of an antithyroid drug, phenylthiocarbamide (PTC). PTC also retarded the growth of the larvae. T4 (0.05 and 0.10 ppm) or T3 (0.01 and 0.02 ppm) therapy removed the PTC-inhibition,albeit not completely, suggesting that thyroid hormones are involved in the larval growth and development of tilapia. PMID- 24213823 TI - Annual variations in brain serotonin and related compounds of domesticated rainbow trout (Oncorhynchus mykiss). AB - The levels of tryptophan (Trp), 5-hydroxytryptamine (serotonin, 5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) in two brain regions (hypothalamus and medulla oblongata) of rainbow trout (Oncorhynchus mykiss) were measured throughout the year using a sensitive high performance liquid chromatographic method with electrochemical detection. Trp was also quantified in serum, liver and brain regions. Trp concentrations were higher in sera than in tissues (brain and liver) throughout the year. Hypothalamic and medullary Trp offered similar annual patterns showing two peaks, the first on 10 May and the second on 15 June. 5-HT levels were always higher in the hypothalamus than in the medulla and much higher than the 5-HIAA levels in both regions. Moreover hypothalamic and medullar serotonin patterns were very different, in the latter region few variations were observed. In addition, the 5-HIAA/5-HT ratio was different in the brain regions, the hypothalamus showed two peaks (April 8 and June 15) whereas the equivalent was not observed in the medulla. All measured compounds showed significant variations during the year. PMID- 24213825 TI - Role of thyroid hormones in tilapia larvae (Oreochromis mossambicus): II. Changes in the hormones and 5'-monodeiodinase activity during development. AB - Thyroid hormone profiles and 5'-monodeiodinase activity were determined in tilapia at different stages of early development. The results showed that both T4 and T3 were present in significant amounts in fertilized eggs. There was a steady decrease in both T4 and T3 levels during embryonic development. The levels continued to decline after hatching until around 7 days later when most of the yolk had been absorbed. The T4 level started to rise then, suggesting that the larval thyroid had begun to produce T4 at this time, which coincided with the period of faster growth of the larvae. The T3 level remained fairly constant until around 20 days after which it rose significantly. In vitro determination of 5'-monodeiodinase activity (5'-D activity) in the whole-body homogenates of larvae showed that the enzymatic conversion of T4 to T3 was not detectable in eggs and 3-day-old larvae but detected in 5-day-old and older larvae. There was a gradual increase in the Vmax as development proceeded indicating increasing 5'-D activity during larval development. The Km values did not differ significantly in the different stages of development. These results are discussed in relation to the growth and development of the larvae. PMID- 24213826 TI - Progestogen metabolism by ovaries of the roach (Rutilus rutilus L.) and the rudd (Scardinius erythrophthalmus L.). AB - Roach ovaries converted 17-hydroxyprogesterone to 17,20alpha-dihydroxy-4-pregnen 3-one (17,20alphaP) and to glucuronides of testosterone and 17,20alphaP. Small amounts of 5alpha-pregnane-3alpha- and -3beta, 17, 20alpha-triols, 7alpha-hydroxy 5alpha-reduced metabolites and 17,20beta-dihydroxy-4-pregnen-3-one (17,20betaP) were also formed. Rudd ovaries converted this substrate mainly to 17,20alphaP, 5alpha-pregnane-3alpha- and -3beta,17,20alpha-triols, 17,20alpha-dihydroxy-5alpha pregnan-3-one and testosterone glucuronide. The main metabolites of progesterone with both species were 17,20alphaP, 5alpha-pregnane-3beta,17,20alpha-triol and 7alpha-hydroxy-5alpha-reduced steroids. Rudd ovaries formed, in addition, 17,20alpha-dihydroxy-5alpha-pregnan-3-one from progesterone. The pattern of metabolites was markedly altered when the concentration of substrate was increased from 42ng to 1 ug or 100 ug. At the highest concentration, glucuronides and polar steroids were not detectable, while at low concentrations they accounted for over 50% of the metabolites. 20alpha-Hydroxysteroid dehydrogenase was shown to have a very high capacity, producing 21-47 ug 17,20alphaP from 100 ug 17-hydroxyprogesterone substrate with 200 mg ovarian tissue in 5h. PMID- 24213827 TI - Oocyte maturation inClarias batrachus. III. Purification and characterization of maturation-inducing steroid. AB - Maturation-inducing steroid (MIS) in the Indian female catfish,Clarias batrachus, was purified and characterized from the incubation medium in which fully grown but immature folliculated oocytes were incubated with salmon gonadotropin (SG G100) for 36 h. Maturation-inducing (MI) activity of residues obtained at various steps of extraction and purification was assessed byin vitro germinal vesicle breakdown (GVBD) assay using folliculated oocytes ofC. batrachus. The post incubation medium was extracted with diethyl ether. The ether phase was partitioned using 50% methanol plus n-hexane. The methanol phase which had MI activity was fractionated into 7 fractions using reverse-phase high-performance liquid chromatography. Of these 7 fractions, fraction 3 was found to be active in having MI ability and identified as 17 alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-diOHprog). The authenticity of 17alpha,20beta-diOHprog as the major follicular mediator of gonadotropin-induced oocyte maturation was further confirmed by thin-layer chromatography (TLC) in which fraction 3 was run along with authentic 17alpha,20beta-diOHprog standard. This investigation gives a direct evidence that 17alpha,20beta-diOHprog is the major naturally occurring MIS in Indian female catfish,C. batrachus. PMID- 24213828 TI - Effects of dietary testosterone on growth and sex ratio in juvenile Atlantic salmon (Salmo salar). AB - Diets to which testosterone (1 or 10 ng/g diet) had been added were fed to juvenile Atlantic salmon (Salmo salar) for nine months beginning for months after hatching (Experiment 1) and upon completion of yolk absorption (Experiment 2) to determine the effects on growth, gonadal development, and sex ratio. Dietary testosterone at 10 ng/g fed to juvenile salmon at four months after hatching (Exp. 1) induced significant changes in condition factor (0.69+/-0.01) compared to controls (0.79+/-0.01) at the end of the test period. In both experiments, salmon treated with 10 ng/g diet induced a significantly higher percentage of male fish compared to controls. Dietary testosterone at 1 ng/g fed to juvenile salmon beginning four months after hatching induced significant increases in weight (18.95+/-0.99) and length (13.58+/-0.23) compared to controls (14.55+/ 1.50 and 11.94+/-0.43, respectively). In Experiment 1 or 2, there was no apparent influence of dietary testosterone on precocious male sexual development. Dietary testosterone at 1 or 10 ng/g fed to juvenile salmon upon completion of yolk absorption (Exp. 2) induced no consistent changes in growth in juvenile Atlantic salmon. These studies indicate that low levels of dietary testosterone may influence physiological responses in juvenile Atlantic salmon dependent upon timing of treatment. PMID- 24213829 TI - Association of HSL gene E1-c.276C>T and E8-c.51C>T mutation with economical traits of Chinese Simmental cattle. AB - Hormone-sensitive lipase (HSL) is responsible for the decomposition of triglycerides in adipose tissue to release free fatty acids, and it is a key rate limiting enzyme in the regulation of adipose tissue deposition and decomposition. The objective of this study was to evaluate the association between novel SNPs in the coding region of bovine HSL gene and carcass and meat quality traits of Chinese Simmental-cross steers. Two novel SNPs were genotyped and the 47 traits of carcass and meat quality traits were measured in the population studied. Statistical analysis revealed that the SNPs of HSL gene were associated with the carcass and meat quality traits. The individuals with TT genotypes of E1-276C>T showed significant higher dressing percentage, net meat rate, hind legs circumference, fat coverage rate, mesenteric fat and kidney fat (p < 0.05). E8 51C>T (P17S) also showed a significant association with the pH of beef and fatty acids content in Chinese Simmental cattle (p < 0.01). Our findings indicated that polymorphisms in HSL might be one of important genetic factors that influence carcass yield and meat quality in beef cattle, and it may be a useful marker for meat quality traits in future marker-assisted selection programs in beef cattle breeding and production. PMID- 24213831 TI - Soil sampling and analysis for volatile organic compounds. AB - Concerns over data quality have raised many questions related to sampling soils for volatile organic compounds (VOCs). This paper was prepared in response to some of these questions and concerns expressed by Remedial Project Managers (RPMs) and On-Scene Coordinators (OSCs). The following questions are frequently asked: 1. Is there a specific device suggested for sampling soils for VOCs? 2. Are there significant losses of VOCs when transferring a soil sample from a sampling device (e.g., split spoon) into the sample container? 3. What is the best method for getting the sample from the split spoon (or other device) into the sample container? 4. Are there smaller devices such as subcore samplers available for collecting aliquots from the larger core and efficiently transferring the sample into the sample container? 5. Are certain containers better than others for shipping and storing soil samples for VOC analysis? 6. Are there any reliable preservation procedures for reducing VOC losses from soil samples and for extending holding times? Guidance is provided for selecting the most effective sampling device for collecting samples from soil matrices. The techniques for sample collection, sample handling, containerizing, shipment, and storage described in this paper reduce VOC losses and generally provide more representative samples for volatile organic analyses (VOA) than techniques in current use. For a discussion on the proper use of sampling equipment the reader should refer to other sources (Acker, 1974; U.S. EPA, 1983; U.S. EPA, 1986a).Soil, as referred to in this report, encompasses the mass (surface and subsurface) of unconsolidated mantle of weathered rock and loose material lying above solid rock. Further, a distinction must be made as to what fraction of the unconsolidated material is soil and what fraction is not. The soil component here is defined as all mineral and naturally occurring organic material that is 2 mm or less in size. This is the size normally used to differentiate between soils (consisting of sands, silts, and clays) and gravels.Although numerous sampling situations may be encountered, this paper focuses on three broad categories of sites that might be sampled for VOCs: 1. Open test pit or trench. 2. Surface soils (<5 ft in depth). 3. Subsurface soils (>5 ft in depth). PMID- 24213830 TI - The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children. AB - One-third of all individuals with epilepsy are resistant to antiepileptic drug (AED) treatment. Antiepileptic treatment response has been suggested to be modulated by genetic polymorphisms of drug efflux transporters. Several polymorphic variants within the multidrug resistance 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein, have been proposed to be associated with AED resistance in epilepsy patients. The aim of this study was to evaluate the effect of C3435T and G2677T/A polymorphisms of MDR1 on AED resistance in Turkish children with epilepsy. MDR1 C3435T and G2677T/A were genotyped in 152 patients with epilepsy, classified as drug-resistant in 69 and drug-responsive in 83. Genotypes of the C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction followed by restriction fragment length polymorphism. Genotype and allele frequencies of C3435T and G2677T/A polymorphisms of the MDR1 gene did not differ between drug-resistant and drug responsive epilepsy patients. Our results suggest that MDR1 C3435T and G2677T/A polymorphisms are not associated with AED resistance in Turkish epileptic patients. To clarify the exact clinical implication of the MDR1 polymorphisms on the multidrug resistance in epilepsy, further investigations in various ethnic populations would be necessary. PMID- 24213832 TI - Foliar injury air pollution surveys of eastern white pine (Pinus strobus L.): A review. AB - A thorough review and critical evaluation of field surveys from 1900 to the present of foliar injury to Pinus strobus L. supposedly caused by air pollution was undertaken. Ninety percent of the surveys failed to meet current scientific standards of acceptability. The conduct and peer review of surveys has been poor and the correct injury symptoms have not always been used. Data were obtained for nine that met screening criteria and injury incidence and severity were mapped. Three fourths of the counties in the natural and planted range of eastern white pine have not been scientifically surveyed, so generalizations regarding large scale spatial patterns of eastern white pine foliar pathological conditions were not possible. However, recent growth and inventory data indicate that growth throughout the natural range regardless of air pollution or other stresses (e.g. blister rust) is excellent, suggesting that regional performance and foliar conditions are unrelated. Sufficient compelling corroborative evidence was found to conclude that a general decline of eastern white pine throughout its range is not a tenable finding.The putative air pollution sensitivity of eastern white pine appears to be based on studies published between 1963 and 1973 on hypersensitive individuals that are no longer being observed in the field. More recent research on eastern white pine has noted a lack of sensitivity and/or high variability of response. The idea that eastern white pine as a species is highly sensitive to air pollution is no longer supported by the available evidence. However, hypersensitive juvenile individuals comprising no more than 8-9% of the total population may still germinate and grow for a brief period of time (because old enough parent trees are still alive) but soon succumb to current levels of ozone and sulfur dioxide in the environment or are suppressed by tolerant neighbors. This phenomenon has been documented anecdotally and is more aptly called tree decline instead of forest decline. An emerging working hypothesis to explain recent reports of unusual eastern white pine tolerance is that sufficient time has elapsed for tree decline to have occurred leading to a gradual elimination of sensitive genotypes from populations. PMID- 24213833 TI - Criteria for the evaluation of alternative environmental monitoring variables: Theory and an application using winter flounder (Pleuronectes americanus) and Dover sole (Microstomus pacificus). AB - The design of environmental monitoring programs is frequently hampered by a lack of objective, quantitative criteria for evaluating alternative monitoring variables. In this paper we describe two such criteria, which we call samples required - the number of samples required to detect a given change in value - and information imparted - the amount of environmental information revealed by the monitoring variable. We then use these criteria to evaluate fin erosion in winter flounder (Pleuronectes americanus) and Dover sole (Microstomus pacificus) as marine environmental monitoring variables. Two methods for determining the samples required use contaminated and reference areas to estimate the sample statistics of a hypothetical impacted population. The first method is based on the overall difference in the proportions of diseased fish in the reference and hypothetical populations. The second treats the proportion of diseased fish in individual trawls as the variate and determines the samples required based on the mean and variance of the reference and contaminated populations. We use both methods to predict the number of trawls needed to detect an increase of 200% in fin erosion in the reference population. The first method had greater statistical power but assumes spatially homogeneous populations. The second method accounts for environmental patchiness. For Dover sole it predicted 1661 trawls would be needed to detect the 200% increase. An estuarine winter flounder population would require 74 trawls, and an oceanic winter flounder population would require 142.5 trawls. It appears that fin erosion in winter flounder may be a useful indicator of environmental contamination, but several stipulations apply. Migration may inflate the number of diseased fish observed in the reference population, and a more detailed etiology of the disease is required, including an understanding of what contaminants are responsible for manifestation of the disease. PMID- 24213834 TI - Effects of exposure of aquatic snails to sublethal concentrations of waste drilling fluid. AB - Static bioassays were carried out using two aquatic snails (Pilia sp. and Lanistes sp.) as test organisms in soft natural dilution water, with waste drilling fluid as the test material, at 28+/-2 degrees C. Comparison of results for the control and different concentrations of the waste drilling fluid were made by means of the F-statistic method. The waste drilling fluid was practically non-toxic to the two aquatic snails. PMID- 24213835 TI - Molecular characterization and genome-wide mutations in porcine anal atresia candidate gene GLI2. AB - Anal atresia (i.e., anorectal malformations) is a severe disorder that occurs during the development of the distal hindgut in infants, swine, and many other mammals and has an unclear genetic background. Recently, the Shh-responsive transcription factor GLI2 has been shown as essential to the normal development of the hindgut, and QTL studies in pigs revealed that this gene may be an important candidate for anal atresia (AA). We used the pig as the model to study the contribution of GLI2 to AA. We revealed the genomic structure of the porcine GLI2 gene with 14 exons and obtained the porcine GLI2 mRNA sequence with a 4,656 bp ORF coding a 1,551-amino acid protein. We further scanned the genome-wide mutations in this gene by direct sequencing using three genomic DNA pools from the AA pigs, full-sibs of AA pigs, and unaffected pigs, respectively. Finally, 30 single nucleotide polymorphisms (SNPs) and one intronic 9-nucleotide (nt) deletion were identified. Of these SNPs, 23 are intronic, 6 are synonymous, and 1 (446 G>A) in exon 8 is nonsynonymous (365Met >Ile). NCOI-RFLP of the 446 G>A polymorphism suggested that the predominant genotypes were all GG and AG in the three pig groups. In addition, there was no significant difference among the three groups in allele frequencies, which demonstrated that this locus was not associated with AA in pigs. However, the 12 SNPs encompassing exon 4 to exon 8 showed strong linkage disequilibrium in the AA pigs, which indicated that the mutations somewhere in this region may contribute to AA in pigs. Therefore, further investigation in this region is needed to elucidate the underlying mutations involved in the porcine AA. PMID- 24213836 TI - Fish from Missouri's lead belt: To eat or not to eat. AB - Data collected over the past four years indicate that filets of suckers and some species of sunfish taken from certain sites in Missouri's Old Lead Belt consistently contain elevated lead concentrations which exceed the limit of 0.3 MUg/g suggested by the World Health Organization. The problem exists in bottom feeding species taken from some sites along the Big River affected by erosion from abandoned lead tailings piles. Fish from many other sites within the Old Lead Belt and the New Lead Belt, including current wastewater treatment systems, are within the acceptable limits for lead in food. Public health implications are discussed relative to observed lead concentrations and available data regarding lead toxicity to humans. PMID- 24213837 TI - Long-term effects of application of sewage sludge to soil on composition of herbage with respect to potentially toxic elements. AB - Repeated applications of metal-contaminated sewage sludge can have a drastic effect on soil levels of trace elements and lead to serious toxicity effects in plants. In some cases, land can be rendered sterile.It has been demonstrated that contamination of soils with respect to cadmium, copper, lead, mercury, nickel and zinc is largely irreversible, although there does appear to be a long-term tendency for these metals to become progressively less available to plants over a long period of time. Most national guidelines designed to regulate the disposal of sewage sludge on agricultural land are based on the assumption that relatively rapid fixation of contaminant metals does take place in the soil after sludge application. There is a dearth of information relating to the rates at which potentially toxic-elements commonly present in sewage sludge become immobilised in soils, although it is clear that contaminant boron can be leached down the profile in the short term.Evidence is presented that contamination of top soil can persist for a period of six years after a single application of sludge (150 tonnes dry matter/ha). Over this period, there was little change in 'available' levels of boron, cadmium, copper, lead and zinc in the top soil and the degree of enhancement of these elements in perennial ryegrass grown in the sludge-treated area remained more or less unchanged. PMID- 24213838 TI - Vanadium uptake by higher plants: Some recent developments. AB - The occurrence of vanadium in the biosphere, and the possible roles this element may play in the metabolism of living organisms, especially higher plants, are discussed. The aqueous chemistry of the element is reviewed, and the chemical properties of the element are related to those of soils and plants. Evidence is present for a biotransformation of vanadium from vanadate (VO 3 (-) ) to vanadyl (VO(2+)) during uptake by plants, based on tissue analysis and ESR spectra. The significance of this process on the potential impact of vanadium in the biosphere is discussed. PMID- 24213839 TI - Trace element distribution and mobilization in Scottish soils with particular reference to cobalt, copper and molybdenum. AB - Total and extractable trace element contents have been determined in about 1000 soil profiles representing the main soil series occurring throughout Scotland. The frequency distributions of a number of trace elements in these soils are described and some relationships between total and extractable contents discussed. The geological nature of the soil parent material, soil texture, organic matter content and environmental contamination are the principal factors controlling soil total contents. Soil drainage class, because of its effect on mineral weathering and soil oxidation-reduction conditions, has a major influence on soil extractable contents, availability to plants and crop uptake. Particular attention is paid to cobalt, copper and molybdenum because of their importance for animal health in Scotland. PMID- 24213840 TI - Demethylation effect of the antineoplaston AS2-1 on genes in colon cancer cells. AB - Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. antineoplastons have been shown to control neoplastic growth. In the present study, we investigated demethylation effect of the antineoplaston AS2-1 (a mixture of phenylacetylglutamine and phenylacetate in the ratio of 1:4) on various genes in colon cancer cells. An HpaII-MspI methylation microarray was used to investigate the methylation status of 51 genes at the promoter region in HCT116 and KM12SM human colon cancer cells before and after treatment of AS2-1. The expression of protein and mRNA of the demethylated genes by AS2-1 in HCT116 cells was evaluated. In 19 of the 34 methylated genes in HCT116 and in 7 of the 8 methylated genes in KM12SM, the methylation status was downregulated after treatment with 2 mg/ml of AS2-1 for 24 h. AS2-1 dramatically downregulated the methylation status of p15 and ESR1 in HCT116 cells and of MTHFR and MUC2 in KM12SM cells. Both mRNA and protein expression of p15 increased in a dose- and time-dependent manner after treatment with AS2-1. The antineoplaston AS2-1 may normalize the hypermethylation status at the promoter region in various genes including tumor suppressor genes, resulting in activation of the transcription and translation in colon cancer. PMID- 24213841 TI - Lack of ciliary body lymphatics in iridociliary melanocytoma. PMID- 24213842 TI - Aryl hydrocarbon receptor (AhR) inducers and estrogen receptor (ER) activities in surface sediments of Three Gorges Reservoir, China evaluated with in vitro cell bioassays. AB - Two types of biological tests were employed for monitoring the toxicological profile of sediment cores in the Three Gorges Reservoir (TGR), China. In the present study, sediments collected in June 2010 from TGR were analyzed for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated activities. The estrogenic activity was assessed using a rapid yeast estrogen bioassay, based on the expression of a green fluorescent reporter protein. Weak anti-estrogenic activity was detected in sediments from an area close to the dam of the reservoir, and weak estrogenic activities ranging from 0.3 to 1 ng 17beta estradiol (E2) equivalents (EQ) g(-1) dry weight sediment (dw) were detected in sediments from the Wanzhou to Guojiaba areas. In the upstream areas Wanzhou and Wushan, sediments demonstrated additive effects in co-administration of 1 nM E2 in the yeast test system, while sediments from the downstream Badong and Guojiaba areas showed estrogenic activities which seemed to be more than additive (synergistic activity). There was an increasing tendency in estrogenic activity from upstream of TGR to downstream, while this tendency terminated and converted into anti-estrogenic activity in the area close to the dam. The AhR activity was detected employing rat hepatoma cell line (H4IIE). EROD activities were found homogenously distributed in sediments in TGR ranging from 200 to 311 pg 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) EQ g(-1) dw for total AhR agonists and from 45 to 76 pg TCDD EQ g(-1) dw for more persistent AhR agonists. The known AhR agonists polycyclic aromatic hydrocarbon, polychlorinated biphenyl, and PCDD/F only explained up to 8 % of the more persistent AhR agonist activity in the samples, which suggests that unidentified AhR-active compounds represented a great proportion of the TCDD EQ in sediments from TGR. These findings of estrogenic potential and dioxin-like activity in TGR sediments provide possible weight-of-evidence of potential ecotoxicological causes for the declines in fish populations which have been observed during the past decades in TGR. PMID- 24213843 TI - Effects of in utero di-butyl phthalate and butyl benzyl phthalate exposure on offspring development and male reproduction of rat. AB - The study was conducted to assess the effects of in utero di-butyl phthalate (DBP) and butyl benzyl phthalate (BBP) exposure during late gestation on offspring's development and reproductive system of male rats. Pregnant rats were treated orally with DBP (2, 10, 50 mg/kg), BBP (4, 20, 100 mg/kg), and diethylstilbestrol (DES) 6 MUg/kg (positive control) from GD14 to parturition. A significant reduction in dams' body weight on GD21 in DBP-, BBP-, and DES-treated groups was observed. The gestation length was considerably elevated in the treated groups. Decline in male pups' body weight was significant at PND75 in DBP (50 mg/kg), BBP- (20,100 mg/kg), and DES-treated groups. The weight of most of the reproductive organs and sperm quality parameters was impaired significantly in DBP- (50 mg/kg) and BBP- (100 mg/kg) treated groups. Further, a non significant decline in testicular spermatid count and daily sperm production was also monitored in treated groups. A significant reduction in serum testosterone level in BBP (100 mg/kg), whereas the testicular activity of 17beta-HSD was declined non-significantly in the treated groups with respect to control. The data suggests that DBP and BBP exposure during late gestation period might have adverse effects on offspring's development, spermatogenesis, and steroidogenesis in adult rats. PMID- 24213844 TI - Definition of critical asthma syndromes. AB - Urgent visits to the clinic and emergency department for acute severe asthma exacerbations are all too frequent. Existing national guidelines do not present consistent or specific recommendations for the evaluation and treatment of individual asthma patients in respiratory distress. In this vein, we propose the term "critical asthma syndrome" (CAS) to describe any child or adult who is at high risk for fatal asthma. Acute severe asthma, refractory asthma, status asthmaticus, and near-fatal asthma all describe CAS where physical exhaustion from the overwhelming work of breathing leads to respiratory arrest and death from hypoxia or related complications. The authors of this supplement seek to emphasize the importance of early recognition, prompt and coordinated evaluation, and treatment of CAS in the emergency department, hospital, and intensive care units by experienced healthcare provider teams. CAS is not severe persistent asthma where control of symptoms and prevention of exacerbations are targets of chronic disease management in the outpatient setting. The authors address the distinctions between the two entities throughout the supplement, and elaborate on the considerations important in the care of a critically ill patient, including the common errors to avoid. In addition, gaps in knowledge and clinical experience in regards to critical asthma are highlighted. Knowledge gaps include a lack of understanding of how to recognize CAS, how to coordinate and integrate hospital and outpatient resources, when to further phenotype patients with critical asthma in order to facilitate effective treatment, and how to prevent future acute exacerbations. Lastly, CAS is complicated by the fact that asthma care in diverse healthcare settings is haphazard. We recommend that primary care physicians refer patients promptly to an asthma specialist for consultation to reduce the frequency of acute exacerbations and prevent the development of CAS. PMID- 24213845 TI - Molecular characterization, 3D model analysis, and expression pattern of the CmUBC gene encoding the melon ubiquitin-conjugating enzyme under drought and salt stress conditions. AB - Ubiquitin-conjugating (UBC) enzyme is a key enzyme in ubiquitination. Here, we describe the cloning, characterization, and expression pattern of a novel gene, CmUBC, from a melon. Comparison of the deduced amino acid sequences allowed the identification of highly conserved motifs. Synteny analysis between Cucumis sativus L. and Arabidopsis demonstrated that homologs of several Cucumis UBC genes were found in corresponding syntenic blocks of Arabidopsis. The homology structure model of the CmUBC protein was constructed. UBCs from melon, yeast, and Arabidopsis were highly conserved in their three-dimensional folding. CmUBC was ubiquitously expressed in all melon tissues. Increased transcript levels of CmUBC were observed during drought and salinity stresses, which suggested that the expression of the CmUBC gene in melon plants is responsive to physiological water stress. These results suggested that the CmUBC gene might play an important role in the modulation of the ubiquitination pathway. PMID- 24213846 TI - Molecular phylogeny analysis and species identification of Dendrobium (Orchidaceae) in China. AB - Dendrobium plants are important commercial herbs in China, widely used in traditional medicine and ornamental horticulture. In this study, sequence-related amplified polymorphism (SRAP) markers were applied to molecular phylogeny analysis and species identification of 31 Chinese Dendrobium species. Fourteen SRAP primer pairs produced 727 loci, 97% of which (706) showed polymorphism. Average polymorphism information content of the SRAP pairs was 0.987 (0.982 0.991), showing that plenty of genetic diversity exists at the interspecies level of Chinese Dendrobium. The molecular phylogeny analysis (UPGMA) grouped the 31 Dendrobium species into six clusters. We obtained 18 species-specific markers, which can be used to identify 10 of the 31 species. Our results indicate the SRAP marker system is informative and would facilitate further application in germplasm appraisal, evolution, and genetic diversity studies in the genus Dendrobium. PMID- 24213847 TI - Clostridium difficile infection in children hospitalized due to diarrhea. AB - The frequency of Clostridium difficile infection (CDI)-related hospitalizations is increasing. The aim of this study was to determine the extent of CDI among children hospitalized with diarrhea, risk factors or predictors for severe CDI, the prevalence of NAP1, and to compare the course of CDI depending on bacteria toxicity profile. A retrospective analysis of case records of 64 children (age range 3 months-16 years, median age 2.12 years) with CDI as defined by diarrheal disease and positive polymerase chain reaction (PCR) test (Xpert C. difficile) was conducted. Modified national adult guidelines were used to assess the severity of CDI. CDIs represented 2.7 % of patients with diarrhea (13.5 cases per 1,000 admissions). Thirty-three CDIs (52 %) were community-associated. Antibacterial use preceded CDI in 61 patients (95 %). Seventeen cases (27 %) were binary toxin-positive (CDT+), 13 of which were NAP1 (20.5 %). Over 75 % of CDIs with NAP1 was hospital-acquired, and more often proceeded with generalized infection (p < 0.05). Risk factors for severe CDI (34 %) included NAP1 [odds ratio (OR), 4.85; 95 % confidence interval (Cl), 1.23, 21.86) and co-morbidities (OR, 4.25; 95 % Cl, 1.34, 14.38). Diarrhea >=10 stools daily was associated with severe CDI (p = 0.01). Recurrence occurred in three patients (4.5 %). There was no mortality. C. difficile is an important factor of antibiotic-associated diarrhea in children. Co-morbidities and NAP1 predispose to severe CDI. PMID- 24213849 TI - Imiquimod 5%: a successful treatment for pseudolymphoma. PMID- 24213848 TI - Genetic and phenotypic analysis of Vibrio cholerae non-O1, non-O139 isolated from German and Austrian patients. AB - Vibrio cholerae belonging to the non-O1, non-O139 serogroups are present in the coastal waters of Germany and in some German and Austrian lakes. These bacteria can cause gastroenteritis and extraintestinal infections, and are transmitted through contaminated food and water. However, non-O1, non-O139 V. cholerae infections are rare in Germany. We studied 18 strains from German and Austrian patients with diarrhea or local infections for their virulence-associated genotype and phenotype to assess their potential for infectivity in anticipation of possible climatic changes that could enhance the transmission of these pathogens. The strains were examined for the presence of genes encoding cholera toxin and toxin-coregulated pilus (TCP), as well as other virulence-associated factors or markers, including hemolysins, repeats-in-toxin (RTX) toxins, Vibrio seventh pandemic islands VSP-1 and VSP-2, and the type III secretion system (TTSS). Phenotypic assays for hemolysin activity, serum resistance, and biofilm formation were also performed. A dendrogram generated by incorporating the results of these analyses revealed genetic differences of the strains correlating with their clinical origin. Non-O1, non-O139 strains from diarrheal patients possessed the TTSS and/or the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, which were not found in the strains from ear or wound infections. Routine matrix-assisted laser desorption/ionization (MALDI-TOF) mass spectrometry (MS) analysis of all strains provided reliable identification of the species but failed to differentiate between strains or clusters. The results of this study indicate the need for continued surveillance of V. cholerae non-O1, non-O139 in Germany, in view of the predicted increase in the prevalence of Vibrio spp. due to the rise in surface water temperatures. PMID- 24213850 TI - Association between NQO1 Pro187Ser polymorphism and esophageal cancer: a meta analysis. AB - NAD(P)H: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95% confidence interval (95% CI) was used to assess the association. Twelve case-control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR = 1.24, 95% CI 1.06-1.46, P OR = 0.009; homozygote model: OR = 1.59, 1195% CI 1.10-2.30, P OR = 0.013; dominant model: OR = 1.31, 95% CI 1.05-1.64, P OR = 0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk. PMID- 24213851 TI - "The development tumor model" to study and monitor the entire progression of both primary and metastatic tumors. AB - Glioblastoma multiforme and other malignant cancers resulting in solid tumors continue to be devastating diseases. In order to find more effective treatments, it is necessary to cultivate a better understanding of the dynamics of tumor development in relation to both primary and secondary tumors. Although hand-held or digital caliper methods can measure tumor growth in subcutaneous xenograft models, to date, the only way to follow and monitor the progression of growing tumors in orthotopic animal models is imaging. This is not enough. To improve our knowledge of the biological characteristics that take place during tumor progression at both primary and metastatic sites, it is indispensable to develop an in vivo model which enables us to reproduce, from the beginning to the end of the cancer's natural history, what really happens in a patient affected by a solid tumor. The ideal tumor model must allow us to monitor all the stages of the tumor's development, both in the primary bulk and in secondary locations, by obtaining cells, biopsies as well as performing stainings on sections. In this paper, "the development tumor model", already proposed by the author to monitor the whole progression of the glioblastoma, is also applied to the study of all solid malignancies. It is a xenogeneic orthotopic transplantation model using human tumor-derived cells from the pre-hypoxic phase as transplanted material, which will be cultured in a neurobasal serum-free medium. By transplanting the same material at the same time (time zero) into a number of immunodeficient and genetically identical mice or rats, the model can be used to create a pool of twin animal transplant candidates under the same testing conditions. By sacrificing one animal a week (or choosing other intervals as needed) and performing multiple biopsies and stainings on sections, we can monitor the entire development of both the primary and secondary tumors. This may shed light on which specific cells and particular markers need to be focused on in order to develop innovative, valid therapeutic strategies. PMID- 24213852 TI - Expression of p53 family genes in urinary bladder cancer: correlation with disease aggressiveness and recurrence. AB - p53 is a tumour suppressor gene with an established role in the majority of human neoplasias. Its homologues-p63 and p73-cannot be classified as tumour suppressors, since they encode isoforms with oncogenic properties as well. p63 plays a crucial role in epithelial cell differentiation and p73 is essential for neuronal cell development. The p63 and p73 expressions have been investigated in a variety of human tumours including bladder carcinomas; yet, this is the first study to simultaneously analyse the transcriptional levels of all p53 family members in bladder cancer. Using quantitative real-time polymerase chain reaction, we measured the mRNA expression of p53, p63 and p73 in 30 bladder tumours, each paired with adjacent normal tissue. All three studied genes were up regulated in malignant specimens, p53 by 1.9-fold, p63 by threefold and p73 by twofold, respectively. Further analysis suggested that p63 and p73 act independently of p53 in the malignant bladder epithelium. Statistical analysis revealed that p63 overexpression was more frequent in recurrent bladder tumours (p = 0.045) and in older patients (p = 0.022). Papillary tumours also exhibited abnormal p63 expression (p = 0.026). Finally, p73 was up-regulated in Grade III one-site tumours (p = 0.040). Our results indicate that all p53 family members are abnormally expressed in bladder cancer but do not act synergistically. High levels of p63 correlate with non-muscle invasive tumours with frequent relapses, whereas p73 overexpression is associated with a more aggressive tumour phenotype. PMID- 24213853 TI - The enhanced apoptosis and antiproliferative response to combined treatment with valproate and nicotinamide in MCF-7 breast cancer cells. AB - Acetylation of histone is a major player in epigenetic modifications, resulting in open chromatin structures and, hence, permissive conditions for transcription factor recruitment to the promoters, followed by initiation of transcription. Histone deacetylase inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we examined the antiproliferative effects of valproate with a combination of nicotinamide in the MCF-7 cell line. MCF-7 was treated with various concentrations of valproate. The MTT assay showed that the viability of MCF-7 cells was inhibited and the cell activity was decreased. Viability percent of valproate and nicotinamide combined treatment cells (28 +/- 2) was 1.78 times increased compared with the valproate-alone (0.5 mM) treated cells (50 +/- 2). Colony formation in soft agar indicated that valproate at 0.3 mM, when used alone, weakly suppressed proliferation of cells (82 +/- 3) and the combination treatment of valproate + nicotinamide strongly suppressed cell proliferation (51 +/- 3). The flow cytometric and microscopic analyses of HDACI combined with treated cells indicated strong apoptosis induction and nuclear morphological alterations greater than those of valproate alone. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the efficiency of the HDAC inhibitor combination, revealing the effectively upregulated p16 and p21. Furthermore, to investigate the role of acetyl-histone H3 levels, western blot analyses have been performed and high levels of acetylated histone H3 were detected in valproate- and nicotinamide-treated cells. These results suggest that the combination treatment of valproate with nicotinamide exerts significant antitumor activity and could be a promising therapeutic candidate to treat human breast cancer. PMID- 24213854 TI - Conservation of the critically endangered eastern Australian population of the grey nurse shark (Carcharias taurus) through cross-jurisdictional management of a network of marine-protected areas. AB - Between 2001 and 2009, 26 marine-protected areas (MPA) were established on the east Australian seaboard, at least in part, to manage human interactions with a critically endangered population of grey nurse shark, Carcharias taurus. This network is spread across six MPA systems and includes all 19 sites outlined in the National Recovery Plan for C. taurus, though five sites remain open to some forms of fishing. The reserve network has complex cross-jurisdictional management, as the sharks occur in waters controlled by the Australian states of New South Wales (NSW) and Queensland, as well as by the Commonwealth (Federal) government. Jurisdiction is further complicated by fisheries and conservation departments both engaging in management activities within each state. This has resulted in protected area types that include IUCN category II equivalent zones in NSW, Queensland, and Commonwealth marine parks that either overlay or complement another large scaled network of protected sites called critical habitats. Across the network, seven and eight rule permutations for diving and fishing, respectively, are applied to this population of sharks. Besides sites identified by the recovery plan, additional sites have been protected as part of the general development of MPA networks. A case study at one of these sites, which historically was known to be occupied by C. taurus but had been abandoned, appears to shows re-establishment of an aggregation of juvenile and sub-adult sharks. Concurrent with the re-establishment of the aggregation, a local dive operator increased seasonal dive visitation rates at the site fourfold. As a precautionary measure, protection of abandoned sites, which includes nursery and gestating female habitats are options that may assist recovery of the east coast population of C. taurus. PMID- 24213855 TI - Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles. AB - Recent studies have shown that irreversible inhibition of Nek2 kinase [(Never in mitosis gene a)-related kinase 2], overexpression of which is observed in several cancers, can be achieved using Michael acceptors containing an ethynyl group, which target the enzyme's cysteine 22 residue lying near the catalytic site. The model studies described herein demonstrate an analogous capture of the ethynyl moiety in a series of ethynyl-heterocycles (e.g. 6-ethynyl-N-phenyl-9H-purin-2 amine) by N-acetylcysteine methyl ester in the presence of 1,4 diazabicyclo[2.2.2]octane in either dimethyl sulfoxide or N,N-dimethylformamide. Kinetic studies showed a 50-fold range in reactivity with 7-ethynyl-N-phenyl-3H [1,2,3]triazolo[4,5-d]pyrimidin-5-amine being the most reactive compound, whereas 4-ethynyl-N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine was the least reactive. Studies of the isomeric compounds, 2-(3-((6-ethynyl-7-methyl-7H-purin-2 yl)amino)phenyl)acetamide and 2-(3-((6-ethynyl-9-methyl-9H-purin-2 yl)amino)phenyl)acetamide, revealed the N(7)-methyl isomer to be 5-fold more reactive than the 9-methyl isomer, which is ascribed to a buttressing effect in the N(7)-methyl compound. Comparison of the crystal structures of these isomers showed that the ethynyl group is significantly displaced away from the methyl group exclusively in the N(7)-methyl isomer with an sp(2) bond angle of 124 degrees , whereas the corresponding angle in the N(9)-methyl isomer was the expected 120 degrees . The results of this study indicate heterocyclic scaffolds that are likely to be more promising for inhibition of Nek2 and other kinases containing a reactive cysteine. PMID- 24213856 TI - Physiological mechanisms of sex differences in exertional dyspnoea: role of neural respiratory motor drive. AB - NEW FINDINGS: What is the central question of this study? Does the combination of a higher neural respiratory drive and greater dynamic mechanical ventilatory constraints during exercise in healthy women versus men form the mechanistic basis of sex differences in activity-related dyspnoea? What is the main finding and its importance? Sex differences in activity-related dyspnoea in health primarily reflected the awareness of a higher neural respiratory drive needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical ventilatory constraints in women. These findings may have implications for our understanding of the mechanisms of sex differences in exertional dyspnoea in variants of health (e.g. the elderly) and in patients with cardiorespiratory disease. The purpose of this study was to elucidate the physiological mechanisms of sex differences in exertional dyspnoea. We compared detailed measures of neural respiratory motor drive [diaphragmatic EMG (EMGdi) expressed as a percentage of maximal EMGdi (EMGdi%max)], breathing pattern, operating lung volumes, dynamic respiratory mechanics [tidal oesophageal (P(oes,tida)l%peak) and transdiaphragmatic pressure swings (P(di,tidal)%peak) expressed as a percentage of their respective peak values] and sensory intensity and unpleasantness ratings of dyspnoea during symptom-limited incremental cycle exercise in healthy young women (n = 25) and men (n = 25). The tidal volume to forced vital capacity ratio (V(T)%FVC), breathing frequency, EMGdi%max, P(oes,tidal)%peak, P(di,tidal)%peak and sensory intensity and unpleasantness ratings of dyspnoea were higher, while dynamic inspiratory capacity and inspiratory reserve volume were lower at a standardized absolute ventilation of 55 l min(-1) during submaximal exercise in women versus men (all P < 0.05). In contrast, sex had no demonstrable effect on the inter-relationships between exercise-induced increases in V(T)%FVC, EMGdi%max and sensory intensity and unpleasantness ratings of dyspnoea. The results of this study suggest that sex differences in the intensity and unpleasantness of exertional dyspnoea in health are likely to reflect the awareness of a relatively higher neural respiratory motor drive (or EMGdi%max) needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical constraints on V(T) expansion in women. PMID- 24213857 TI - Exercise training and vascular cell phenotype in a swine model of familial hypercholesterolaemia: conduit arteries and veins. AB - NEW FINDINGS: What is the central question of this study? Does endurance exercise training cause anti-atherogenic effects on the endothelium in a swine model of familial hypercholesterolaemia (FH), and how are these effects distributed across veins, arteries and multiple vascular territories within each system? What is the main finding and its importance? Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control animals, and exercise training did not change vasomotor function within FH. In systemic conduit arteries and veins, few effects of FH on endothelial cell protein expression were noted, including both pro- and anti-atherogenic changes. These findings suggest that exercise training does not produce a consistently improved endothelial cell phenotype in either coronary or systemic conduit vessels in this swine model of FH. Exercise training has emerged as an intervention for the primary and secondary prevention of coronary artery disease, but the mechanisms through which training reduces relative risk are not completely understood. The goal of this study was to investigate the impact of endurance exercise training on vasomotor function and vascular cell phenotype in coronary arteries and systemic conduit arteries and veins against a background of advanced atherosclerosis. We tested the hypothesis that exercise training restores endothelial vasomotor function and produces an anti-atherogenic endothelial and smooth muscle cell phenotype in familial hypercholesterolaemic (FH) swine. The study included 30 FH (15 exercised and 15 sedentary) and 13 non FH control male castrated swine. The exercise-training intervention consisted of treadmill running 5 days per week for 16-20 weeks. Tissues sampled at sacrifice included vascular rings from the coronary circulation for vasomotor function experiments (dose-dependent bradykinin-induced vasorelaxation) and endothelial cells (ECs) from isolated segments of the thoracic aorta, the carotid, brachial, femoral and renal arteries, as well as each corresponding regionally associated vein, and from the abdominal vena cava, the right coronary and internal mammary arteries. Smooth muscle cells were sampled from the right coronary artery only. Vascular cell phenotype was assessed by immunoblotting for a host of both pro- and anti-atherogenic markers [e.g. endothelial nitric oxide synthase, p67phox, superoxide dismutase 1 (SOD1)]. Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control pigs, and exercise training did not change vasomotor function within FH. In contrast, only scattered effects of FH on EC phenotype were noted across the vasculature, which included both pro- and anti-atherogenic changes in EC protein expression (e.g. increased endothelial nitric oxide synthase in carotid artery ECs, decreased p67phox in brachial artery ECs, but decreased expression of the antioxidant protein SOD1 in thoracic vena cava; all P < 0.05). In thoracic vena cava ECs, this deficit was corrected by exercise training, while no other effects of exercise were observed in conduit vessel EC phenotype. Thus, while exercise training abrogated the adverse effect of hypercholesterolaemia on thoracic vena cava SOD1 expression, it appears that exercise training does not produce a consistently improved EC phenotype in either coronary or systemic conduit vessels in this FH swine model. PMID- 24213858 TI - Modifiers of heart and muscle function: where genetics meets physiology. AB - New Findings What is the topic of this review? Genetic modifiers act on many different physiological aspects of muscle disease. Understanding and identifying such modifiers is important because their discovery may help to predict the course of muscle disease and also indicate pathways to be exploited in designing new therapeutics. What advances does it highlight? Genetic modifiers have been identified that act primarily on limb skeletal muscles. Newer modifiers, where the responsible gene has yet to be identified, alter the course of cardiopulmonary dysfunction in muscular dystrophy. Distinct modifiers that act differentially on limb skeletal muscles versus heart and respiratory muscles reflect underlying physiological differences of these muscle groups. Many single gene disorders are associated with a range of symptoms that cannot be explained solely by the primary genetic mutation. Muscular dystrophy is a genetic disorder associated with variable outcomes that arise from both the primary genetic mutation and the contribution from environmental and genetic modifiers. Disruption of the dystrophin complex occurs in Duchenne muscular dystrophy and limb girdle muscular dystrophy, producing heart and muscle disease through a cellular injury process characterized by plasma membrane disruption and fibrosis. Multiple modifier loci have been mapped by using a mouse model of muscular dystrophy. These modifiers exert their effect often on specific muscle groups targeted by the muscular dystrophy process, possibly reflecting distinct pathophysiological processes among muscle groups. Genetic modifiers act on both cardiac and respiratory muscle parameters, suggesting genetic and physiological integration of cardiopulmonary function. Skeletal muscles of the limbs are modified by a locus on mouse chromosome 7. This region of chromosome 7 harbours an insertion/deletion polymorphism in Ltbp4, the gene encoding latent transforming growth factor beta binding protein 4. LTBP4 exerts its effect in muscle disease by acting on plasma membrane stability and fibrosis, thereby linking instability of the sarcolemma directly to fibrosis. In the human muscle disease Duchenne muscular dystrophy, protein coding single-nucleotide polymorphisms in LTBP4 associate with prolonged ambulation, demonstrating that modifiers identified from mouse studies translate to human disease. PMID- 24213859 TI - Noradrenaline and neuropeptide Y contribute to initial, but not sustained, vasodilatation in response to local skin warming in humans. AB - NEW FINDINGS: What is the central question of this study? Previous work has produced the counterintuitive finding that the vasoconstrictor neurotransmitters noradrenaline and neuropeptide Y are involved in vasodilatation. We aimed to discover whether sympathetic neurotransmitters are required for the sustained vasodilatation in response to local skin warming, as has been previously suggested, and to determine whether noradrenaline and neuropeptide Y are 'mediating' the sustained vasodilator response directly or acting to 'prime' (or kick-start) it. What is the main finding and its importance? We have found that noradrenaline and neuropeptide Y are required at the initiation of vasodilatation in response to local skin warming, if a complete vasodilator response is to be achieved; however, they are not required once vasodilatation has begun. In a three-part study, we examined whether noradrenaline, neuropeptide Y (NPY) and endothelial nitric oxide synthase (eNOS) were involved in the sustained vasodilatation in response to local skin warming. Forearm skin sites were instrumented with intradermal microdialysis fibres, local skin heaters and laser Doppler flow probes. Local skin temperature (T(loc)) was increased from 34 to 42 degrees C at a rate of 0.5 degrees C (10 s)(-1). Laser-Doppler flow was expressed as cutaneous vascular conductance (CVC; laser-Doppler flow/mean arterial pressure). In part 1, three skin sites were prepared; two were treated with the study vehicle (lactated Ringer solution), while the third site was treated with yohimbine and propranolol to antagonize alpha- and beta-receptors, and 10 min of baseline data were record at a T(loc) of 34 degrees C. Receptor antagonism was confirmed via infusion of clonidine. The T(loc) was increased to 42 degrees C at all sites. Once CVC had stabilized, site 2 was treated with yohimbine and propranolol to examine the effect of adrenergic receptor blockade on sustained vasodilatation of the skin. Receptor antagonism was again confirmed via infusion of clonidine. All sites were treated with sodium nitroprusside, and T(loc) was increased to 43 degrees C to elicit maximal vasodilatation. In parts 2 and 3, the general protocol was the same, except that BIBP-3226 was used to antagonize Y(1) receptors, NPY to test the efficacy of the antagonism, N(G)-amino-l-arginine to inhibit eNOS and ACh to test the adequacy of inhibition. Compared with control conditions, antagonism of alpha- and beta-receptors, Y(1)-receptors and eNOS before local skin warming reduced the initial and sustained vasodilatation in response to increased T(loc). However, treatment with yohimbine and propranolol or BIBP-3226 after local skin warming did not affect the sustained vasodilatation [CVC, 90 +/- 3 versus 89 +/- 3%max (control vs. yohimbine and propranolol) and 88 +/- 5 versus 87 +/- 4%max (control vs. BIBP-3226); P > 0.05]. N(G)-Amino-l arginine perfusion caused a large reduction in CVC during this phase (89 +/- 5 versus 35 +/- 4%max; P < 0.05). These data indicate that if their actions are antagonized after local warming and cutaneous vasodilatation has occurred, noradrenaline and NPY play little, if any, role in the sustained vasodilatation in response to local skin warming. However, eNOS contributes markedly to the sustained vasodilatation regardless of when it is inhibited. PMID- 24213860 TI - Extracellular calcium chelation and attenuation of calcium entry decrease in vivo cholinergic-induced eccrine sweating sensitivity in humans. AB - NEW FINDINGS: What is the central question of this study? Calcium is an important second messenger in eccrine sweating; however, whether modulation of extracellular Ca(2+) and Ca(2+) entry has the capacity to modulate sweat rate in non-glabrous human skin has not been explored. What is the main finding and its importance? Acetylcholine to sweat rate dose-response relationships identify that local in vivo Ca(2+) chelation and L-type Ca(2+) channel antagonism have the capacity to attenuate the cholinergic sensitivity of eccrine sweat glands. Importantly, these data translate previous glabrous in vitro animal studies into non-glabrous in vivo human skin. Calcium is an important second messenger in eccrine sweating, with both internal and external sources being identified in vitro. It is unclear whether in vivo modulation of extracellular Ca(2+) levels or influx has the capacity to modulate sweat rate in non-glabrous human skin. To test the hypothesis that lowering interstitial Ca(2+) levels would decrease the sensitivity of the ACh to sweat rate (via capacitance hygrometry) dose-response relationship, nine healthy subjects received six ACh doses (1 * 10(-5) to 1 * 10(0) m in 10-fold increments) with and without a Ca(2+) chelator (12.5 mg ml(-1) EDTA) via forearm intradermal microdialysis (protocol 1). To test the hypothesis that attenuating Ca(2+) influx via L-type Ca(2+) channels would also decrease the sensitivity of the ACh to sweat rate dose-response relationship, 10 healthy subjects received similar ACh doses with and without a phenylalkylamine Ca(2+) channel blocker (1 mm verapamil; protocol 2). Non-linear regression curve fitting identified a right-shifted ED50 in EDTA-treated sites compared with ACh alone ( 1.0 +/- 0.1 and -1.5 +/- 0.1 logm, respectively; P < 0.05), but unchanged maximal sweat rate (0.60 +/- 0.07 and 0.58 +/- 0.11 mg cm(-2) min(-1), respectively; P > 0.05) in protocol 1. Protocol 2 also resulted in a right-shifted ED(50) (verapamil, -0.9 +/- 0.1 logm; ACh alone, -1.6 +/- 0.2 logm; P < 0.05), with unchanged maximal sweat rate (verapamil, 0.45 +/- 0.08 mg cm(-2) min(-1); ACh alone, 0.35 +/- 0.06 mg cm(-2) min(-1); P > 0.05). Thus, local in vivo Ca(2+) chelation and L-type Ca(2+) channel antagonism have the capacity to attenuate in vivo cholinergic sensitivity of eccrine sweat glands. These data suggest that interstitial Ca(2+) and its influx via Ca(2+) channels play a functional role in eccrine sweating in intact non-glabrous human skin. PMID- 24213862 TI - Beyond HERA: Contributions of specific prefrontal brain areas to long-term memory retrieval. AB - Recent neuroimaging studies have provided a wealth of information about areas within prefrontal cortex involved in long-term memory. These studies prompted a proposal by Tulving and colleagues (Tulving, Kapur, Craik, Habib, & Houle, 1994) that prefrontal contributions to memory function are related to laterality differences (the hemispheric encoding/retrieval asymmetry model). This review goes beyond a general characterization of prefrontal lobes to a more specific analysis of distinct areas within the prefrontal cortex. Separate prefrontal areas, sometimes within the same hemisphere, are discussed in terms of selective contributions that they might make to memory retrieval. In the end, it is concluded that a framework which tries to understand prefrontal function in terms of specific areas is a useful complement to models, like HERA, which attempt to find unifying principles across multiple areas. PMID- 24213861 TI - PET studies of encoding and retrieval: The HERA model. AB - We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval. PMID- 24213863 TI - Recall of rapidly presented random chess positions is a function of skill. AB - A widely cited result asserts that experts' superiority over novices in recalling meaningful material from their domain of expertise vanishes when they are confronted with random material. A review of recent chess experiments in which random positions served as control material (presentation time between 3 and 10 sec) shows, however, that strong players generally maintain some superiority over weak players even with random positions, although the relative difference between skill levels is much smaller than with game positions. The implications of this finding for expertise in chess are discussed and the question of the recall of random material in other domains is raised. PMID- 24213864 TI - Triangles in ROC space: History and theory of "nonparametric" measures of sensitivity and response bias. AB - Can accuracy and response bias in two-stimulus, two-response recognition or detection experiments be measured nonparametrically? Pollack and Norman (1964) answered this question affirmatively for sensitivity, Hodos (1970) for bias: Both proposed measures based on triangular areas in receiver-operating characteristic space. Their papers, and especially a paper by Grier (1971) that provided computing formulas for the measures, continue to be heavily cited in a wide range of content areas. In our sample of articles, most authors described triangle based measures as making fewer assumptions than measures associated with detection theory. However, we show that statistics based on products or ratios of right triangle areas, including a recently proposed bias index and a not yetproposed but apparently plausible sensitivity index, are consistent with a decision process based on logistic distributions. Even the Pollack and Norman measure, which is based on non-right triangles, is approximately logistic for low values of sensitivity. Simple geometric models for sensitivity and bias are not nonparametric, even if their implications are not acknowledged in the defining publications. PMID- 24213865 TI - Visual perception of markings. AB - Markings, such as designs, writings, diagrams, and depictions, are expressive and communicative human artifacts. The conventional assumption that findings from the study of the visual perception of markings-in particular, of pictures-can be generalized to real-world perception is examined and found to be false. The processes involved in the visual perception of the world and in the visual perception of markings differ in significant ways, and generalizations from one to the other must be undertaken with caution. The visual perception of markings is an identifiable and separate area of study. Implications for a general theory of the perception of markings are examined, and the perception of markings is contrasted with real-world perception. PMID- 24213866 TI - Age differences in encoding and retrieving details of a pediatric examination. AB - Baker-Ward, Gordon, Ornstein, Larus, and Clubb (1993) showed that recall improves over ages 3-7 for events experienced during a physical examination. We used a joint multinomial model to ask whether the improvement was due to encoding, to retrieval, or to likelihood to report. The model fit the Baker-Ward et al. data well and showed that (1) retrieval and reporting cannot be distinguished and (2) the observed effects were due primarily to age-related improvement in retrieval reporting rather than in encoding. PMID- 24213867 TI - Taste reactivity and consumption measures in the assessment of overshadowing: Modulation of aversive, but not ingestive, reactivity. AB - Three dependent measures-a taste reactivity test, a two-bottle preference test, and a one-bottle extinction test-were used to investigate the conditioning effects of pairing a taste/taste compound with LiCl-induced illness in rats. Avoidance of saccharin consumption in the one-bottle test was attenuated if saccharin and denatonium were paired during illness training (overshadowing). Also, saccharin was found to be more palatable if paired with denatonium during training as reflected by aversive (but not ingestive) taste reactivity measures. It is argued that overshadowing was reflected mainly by a modulation of aversive taste reactivity behavior with little influence on ingestive taste reactivity. The results are discussed in terms of current palatability issues, and it is suggested that applying taste reactivity tests to phenomena associated with taste avoidance learning (e.g., overshadowing or potentiation) may further our understanding of the mechanisms that guide such learning. PMID- 24213868 TI - Humans' responses to novel stimulus compounds and the effects of training. AB - Twenty-four college students participated in an experiment with stimulus compounds. Subjects learned to discriminate color stimuli that correlated with varying probabilities of reinforcement. Reinforcement consisted of points. For all subjects, two colors signaled a .80 reinforcement probability, and two others signaled a .20 probability. For compound-trained subjects, a fifth compound stimulus (composed of a high-probability color and a low-probability color) was correlated with a .10 reinforcement probability. During testing, interspersed probe trials required subjects to choose between two alternatives: a compound stimulus and either one of its constituent stimuli. Compound-untrained subjects preferred the compound over either individual stimulus, thus showing response summation. However, compound-trained subjects, having had experience with an exemplar compound, showed significantly lower choice proportions for a test compound, indicating that subjects' responding to novel stimulus compounds is modifiable by experience with a single similar compound. PMID- 24213869 TI - Imagination inflation: Imagining a childhood event inflates confidence that it occurred. AB - Counterfactual imaginings are known to have far-reaching implications. In the present experiment, we ask if imagining events from one's past can affect memory for childhood events. We draw on the social psychology literature showing that imagining a future event increases the subjective likelihood that the event will occur. The concepts of cognitive availability and the source-monitoring framework provide reasons to expect that imagination may inflate confidence that a childhood event occurred. However, people routinely produce myriad counterfactual imaginings (i.e., daydreams and fantasies) but usually do not confuse them with past experiences. To determine the effects of imagining a childhood event, we pretested subjects on how confident they were that a number of childhood events had happened, asked them to imagine some of those events, and then gathered new confidence measures. For each of the target items, imagination inflated confidence that the event had occurred in childhood. We discuss implications for situations in which imagination is used as an aid in searching for presumably lost memories. PMID- 24213870 TI - Perceiving affect from the voice and the face. AB - This experiment examines how emotion is perceived by using facial and vocal cues of a speaker. Three levels of facial affect were presented using a computer generated face. Three levels of vocal affect were obtained by recording the voice of a male amateur actor who spoke a semantically neutral word in different simulated emotional states. These two independent variables were presented to subjects in all possible permutations-visual cues alone, vocal cues alone, and visual and vocal cues together-which gave a total set of 15 stimuli. The subjects were asked to judge the emotion of the stimuli in a two-alternative forced choice task (either HAPPY or ANGRY). The results indicate that subjects evaluate and integrate information from both modalities to perceive emotion. The influence of one modality was greater to the extent that the other was ambiguous (neutral). The fuzzy logical model of perception (FLMP) fit the judgments significantly better than an additive model, which weakens theories based on an additive combination of modalities, categorical perception, and influence from only a single modality. PMID- 24213871 TI - Learning to classify integral-dimension stimuli. AB - The authors tested 288 participants in the classic category-learning tasks introduced by Shepard, Hovland, and Jenkins (1961). However, separable-dimension stimuli were used in previous tests, whereas integral-dimension stimuli were used in the present study. In contrast to previous results, which showed a superiority for Problem Type II over Problem Types III, IV, and V, the reverse pattern was observed in the present research. This result confirms a fundamental prediction made by modern exemplar-based models of classification learning. The results are interpreted in terms of the extent to which selective-attention learning mechanisms operate when separable-dimension versus integral-dimension stimuli are used. PMID- 24213872 TI - Structural alignment in similarity and difference judgments. AB - Similarity is a central construct in models of cognitive processing, and as such has been the focus of psychological inquiry. This work has revealed that similarity and difference judgments are not always inverses. One explanation for this effect is that similarity judgments focus on matching relations between the items, while difference judgments focus on the mismatching attributes. A second explanation is that both similarity and difference judgments involve a process of structural alignment, and that they use the output of this process differently. These views are contrasted by using the one-shot mapping technique that places attribute similarity and relational similarity in competition. The results suggest that similarity and difference judgments both involve structural alignment. PMID- 24213873 TI - On the time course of negative priming: Another look. AB - In two experiments, the pattern of persistence of negative priming effects across delay intervals of 500 and 2,500 msec was assessed using a within-subjects, random sequencing of delays. Neill and Valdes (1992; Neill, Valdes, Terry, & Gorfein, 1992) have argued that a within-subject experimental design is required for decay of negative priming to be seen, in contrast to results reported elsewhere (e.g., Tipper, Weaver, Cameron, Brehaut, & Bastedo, 1991) showing stable negative priming effects across delays. In neither experiment was substantial evidence of decay detected, raising questions for the notion that suppression necessarily declines across brief temporal intervals and for the assertion that episodic retrieval is the sole source of negative priming. PMID- 24213874 TI - Cross-modality priming in stem completion reflects conscious memory, but not voluntary memory. AB - A comparison of incidental and intentional stem-completion tests confirmed that cross-modality priming occurs when performance conforms completely to the retrieval intentionality criterion, indicating involuntary-not voluntary retrieval in the incidental test. However, an on-line measure of awareness in the incidental test, and a process-dissociation analysis of the intentional test, indicated only within-modality, but not cross-modality, transfer of involuntary retrieval that is unaccompanied by memorial awareness. These results imply that conscious memory should not be equated with voluntary retrieval, and unconscious memory should not be equated with involuntary retrieval, because involuntary retrieval can be accompanied by memorial awareness. PMID- 24213875 TI - Eye movement control in reading and visual search: Effects of word frequency. AB - Eye movements were recorded as subjects either read text or searched through texts for a target word. In the reading task, there was a robust word frequency effect wherein readers looked longer at low-frequency words than at high frequency words. However, there was no frequency effect in the search task. The results suggest that decisions to move the eyes during reading are made on a different basis than they are during visual search. Implications for current models of eye movement control in reading are discussed. PMID- 24213876 TI - Semantic priming in visual word recognition: Activation blocking and domains of processing. AB - The fact that letter search on a prime eliminates the typically robust semantic priming effect in lexical decision is often attributed to the "shallowness" of the prime-processing task. In three experiments we investigated this claim by using two different "shallow" prime-processing tasks: letter search and color identification. Consistent with previous reports, lexical decisions to semantically related targets were not facilitated when subjects searched the prime for a probe letter. In contrast, semantic priming was observed following a color discrimination task on the prime. We suggest that a levels-of-processing interpretation is not an adequate framework for understanding these data. Instead, a domain-specific processing account is offered in which explicit processing at the letter level (as in letter search) makes demands on resources (e.g., activation) that drives processing at the semantic level. This competition is resolved by establishing a temporary activation block at the lexical-semantic interface, which results in the elimination or attenuation of semantic priming. In contrast, global judgment of color is viewed as a domain that does not make demands on the resources that drive the visual word recognition machinery. There is therefore no need for an activation block, and semantic priming is not prevented. PMID- 24213877 TI - The bizarre imagery effect and intention to learn. AB - The bizarre imagery effect, better memory for bizarre stimuli than for common stimuli, is now an established finding. However, the mnemonic benefits of bizarre imagery are subject to several constraints (e.g., the use of mixed lists and free recall tests). A further constraint on the bizarreness effect is demonstrated here. In each of two experiments, subjects were given either incidental or intentional study instructions and were asked to rate the vividness of the images they formed from the bizarre and common sentences. Contrary to conclusions based on available evidence, the bizarreness effect in free recall was manifested only with the incidental learning instructions. This additional constraint on the effect is consistent with the item-order account of bizarreness. PMID- 24213878 TI - Protective effect of lycopene on cardiac function and myocardial fibrosis after acute myocardial infarction in rats via the modulation of p38 and MMP-9. AB - Extracellular matrix (ECM) plays an important role in maintaining the left ventricular geometry and ventricular function, and the inhibition of ECM remodeling has therapeutic benefits that could alleviate the progression of ventricular remodeling. Recent studies have indicated that lycopene has cardioprotective effects. In this study, a rat myocardial infarction (MI) model was established by left anterior descending coronary artery ligation. After the operation, the rats received lycopene or saline. After 28 days, the rats underwent echocardiography detection and were sacrificed. Myocardial fibrosis was observed by Masson staining. Type I collagen, MMP-9, and MAPK protein expression were detected in the ischemic zone surrounding the MI by western blot. Treatment with lycopene increased the EF from 45.2 +/- 3.12 % to 51.1 +/- 4.63, and it decreased the LVEDd from 6.52 +/- 0.37 mm to 6.18 +/- 0.41 mm and the LVESd from 4.29 +/- 0.63 to 3.94 +/- 0.37 at 28 days post-myocardial infarction. Lycopene attenuated the MI-induced increase in MMP-9 and type I collagen expression, and inhibited p38 activation. Moreover, lycopene decreased the collagen volume fraction in the peri-infarcted zone. The data indicated that lycopene improved the cardiac function and ventricular remodeling by inhibiting p38 activation and MMP-9 expression. PMID- 24213879 TI - Significance of soluble growth factors in the chondrogenic response of human umbilical cord matrix stem cells in a porous three dimensional scaffold. AB - Stem cell based tissue engineering has emerged as a promising strategy for articular cartilage regeneration. Foetal derived mesenchymal stem cells (MSCs) with their ease of availability, pluripotency and high expansion potential have been demonstrated to be an attractive cell source over adult MSCs. However, there is a need for optimisation of chondrogenic signals to direct the differentiation of these multipotent MSCs to chondrogenic lineage. In this study we have demonstrated the in vitro chondrogenesis of human umbilical cord matrix MSCs in three dimensional PVA-PCL (polyvinyl alcohol-polycaprolactone) scaffolds in the presence of the individual growth factors TGFbeta1, TGFbeta3, IGF, BMP2 and their combination with BMP2. Gene expression, histology and immunohistology were evaluated after 28 d culture. The induced cells showed the feature of chondrocytes in their morphology and expression of typical chondrogenic extracellular matrix molecules. Moreover, the real-time PCR assay has shown the expression of gene markers of chondrogenesis, SOX9, collagen type II and aggrecan. The expression of collagen type I and collagen type X was also evaluated. This study has demonstrated the successful chondrogenic induction of human umbilical cord MSCs in 3D scaffolds. Interestingly, the growth factor combination of TGF-beta3 and BMP-2 was found to be more effective for chondrogenesis as shown by the real-time PCR studies. The findings of this study suggest the importance of using growth factor combinations for successful chondrogenic differentiation of umbilical cord MSCs. PMID- 24213880 TI - Transplantation tolerance. AB - Although transplantation has been a standard medical practice for decades, marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Since the first solid organ transplant between the Herrick twins in 1954, transplantation immunology has sought to move away from harmful, broad-spectrum immunosuppressive regimens that carry with them the long-term risk of potentially life-threatening opportunistic infections, cardiovascular disease, and malignancy, as well as graft toxicity and loss, towards tolerogenic strategies that promote long-term graft survival. Reports of "transplant tolerance" in kidney and liver allograft recipients whose immunosuppressive drugs were discontinued for medical or non-compliant reasons, together with results from experimental models of transplantation, provide the proof-of-principle that achieving tolerance in organ transplantation is fundamentally possible. However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. In this article, we explore the basic science underlying mechanisms of tolerance and review the latest clinical advances in the quest for transplantation tolerance. PMID- 24213881 TI - Pharmacological characterization of N1-(2-methoxyphenyl)-N4-hexylpiperazine as a multi-target antagonist of alpha1A/alpha1D-adrenoceptors and 5-HT1A receptors that blocks prostate contraction and cell growth. AB - Benign prostatic hyperplasia (BPH) is a progressive disease related to the imbalance of cell growth and apoptosis, and it plays a key role in the development of lower urinary tract symptoms (LUTS). The main pharmacological treatment is based on alpha1A-adrenoceptor blockers, but in several cases monotherapy has failed. Recent studies of prostate pathophysiology have noted the role of alpha1D-adrenoceptors and 5-HT1A receptors in prostate cell proliferation in addition to the usual role of alpha1A-adrenoceptors in prostate contraction. N phenylpiperazine is a scaffold structure that may confer drug affinity for these three receptors. Therefore, the present work aimed to investigate the pharmacological characteristics of N1-(2-methoxyphenyl)-N4-hexylpiperazine (LDT66). Using isometric contraction assays with rat prostate and aorta, LDT66 reduced phenylephrine-induced contractions and showed K B values of 3.4 and 2.2 nM for alpha1A- and alpha1D-adrenoceptors, respectively. According to the functional binding assays data, LDT66 showed a high affinity (nanomolar range) for the 5-HT1A receptors, behaving as an antagonist. LDT66 also showed a low affinity (micromolar range) for receptors unrelated to BPH such as alpha1B adrenoceptors, alpha2A-adrenoceptors, muscarinic and 5-HT2A receptors, which is a desirable profile in order to prevent putative side effects. Accordingly, LDT66 (100 MUg/kg) showed a marginal hypotensive effect. Using the DU-145 prostate cells, control experiments characterized the alpha1D-adrenoceptor- and 5-HT1A receptor-mediated cell growth by phenylephrine and 5-HT, respectively. LDT66 (50 nM) prevented both effects similarly. In conclusion, LDT66 is a high-affinity multi-target antagonist of relevant receptors for BPH, and it may be a new starting point for multi-target drug development to treat BPH and LUTS. PMID- 24213882 TI - Do beta-adrenoceptor agonists induce homologous or heterologous desensitization in rat urinary bladder? AB - beta3-Adrenoceptor agonists have recently been introduced for the symptomatic treatment of the overactive bladder syndrome. As such treatment is not curative, long-term treatment is anticipated to be required. As the susceptibility of beta3 adrenoceptors to undergo agonist-induced desensitization is cell type- and tissue dependent, we have explored whether pre-treatment with a beta-adrenoceptor agonist will attenuate subsequent relaxation responses to freshly added agonist using rat urinary bladder as a model. We have used the prototypical beta adrenoceptor agonist isoprenaline, the beta2-selective fenoterol and the beta3 selective CL 316,243 and mirabegron as well as the receptor-independent bladder relaxant forskolin. We show that a 6-h pre-treatment with agonist can significantly reduce subsequent relaxation against KCl-induced smooth muscle tone, but agonist-induced desensitization was also observed with longer pre treatments or against passive tension. The agonist-induced desensitization was prominent for the beta2 component of rat bladder relaxation but much weaker or even absent for the beta3 component. Moreover, beta-adrenoceptor agonist pre treatment reduced contractile responses to the muscarinic agonist carbachol and the receptor-independent stimulus KCl. Taken together these data do not support the hypothesis that the long-term clinical efficacy of beta3-adrenoceptor agonists in the treatment of the overactive bladder syndrome will be limited by receptor desensitization. Rather they raise the possibility that such treatment may not only cause smooth muscle relaxation but also may attenuate hyper contractility of the bladder. PMID- 24213884 TI - Arterial compliance and stiffness following low-intensity resistance exercise. AB - PURPOSE: Although acute high-intensity resistance exercise to exhaustion decreases arterial compliance and increases arterial stiffness, the effect of low intensity resistance exercise (LRE) to exhaustion on arterial compliance and stiffness remains unknown. The present study investigated the acute effects of LRE on arterial compliance and stiffness. METHODS: Ten healthy individuals (age 26 +/- 5 years) performed LRE (40% of 1 repetition maximum) and control (CON: seated rest in the exercise room) trials on separate days in a randomized controlled crossover fashion. The LRE comprised three sets of bench presses to exhaustion with an inter-set rest period of 2 min. In the CON trial, LRE was not performed. Carotid arterial compliance, the beta-stiffness index (via simultaneous B-mode ultrasound and applanation tonometry), carotid and brachial blood pressure and heart rate were measured before and at 30 and 60 min after both trials. RESULTS: Carotid arterial compliance and the beta-stiffness index significantly increased and decreased, respectively (both P < 0.05), at 30 and 60 min after the LRE trials, but neither significantly differed after the CON trials. Carotid and brachial blood pressure and heart rate did not change at 30 and 60 min after both trials from baseline. CONCLUSION: These results suggest that LRE acutely increases arterial compliance and decreases arterial stiffness. PMID- 24213883 TI - Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance. AB - INTRODUCTION: We aimed to manipulate physiological determinants of severe exercise performance. We hypothesized that (1) beta-alanine supplementation would increase intramuscular carnosine and buffering capacity and dampen acidosis during severe cycling, (2) that high-intensity interval training (HIT) would enhance aerobic energy contribution during severe cycling, and (3) that HIT preceded by beta-alanine supplementation would have greater benefits. METHODS: Sixteen active men performed incremental cycling tests and 90-s severe (110 % peak power) cycling tests at three time points: before and after oral supplementation with either beta-alanine or placebo, and after an 11-days HIT block (9 sessions, 4 * 4 min), which followed supplementation. Carnosine was assessed via MR spectroscopy. Energy contribution during 90-s severe cycling was estimated from the O2 deficit. Biopsies from m. vastus lateralis were taken before and after the test. RESULTS: Beta-alanine increased leg muscle carnosine (32 +/- 13 %, d = 3.1). Buffering capacity and incremental cycling were unaffected, but during 90-s severe cycling, beta-alanine increased aerobic energy contribution (1.4 +/- 1.3 %, d = 0.5), concurrent with reduced O2 deficit (-5.0 +/- 5.0 %, d = 0.6) and muscle lactate accumulation (-23 +/- 30 %, d = 0.9), while having no effect on pH. Beta-alanine also enhanced motivation and perceived state during the HIT block. There were no between-group differences in adaptations to the training block, namely increased buffering capacity (+7.9 +/- 11.9 %, p = 0.04, d = 0.6, n = 14) and glycogen storage (+30 +/- 47 %, p = 0.04, d = 0.5, n = 16). CONCLUSIONS: Beta-alanine did not affect buffering considerably, but has beneficial effects on severe exercise metabolism as well as psychological parameters during intense training phases. PMID- 24213886 TI - Global budgets for non-CO2 greenhouse gases. PMID- 24213885 TI - The relationship between body mass index, aerobic performance and asthma in a pre pubertal, population-level cohort. AB - PURPOSE: To assess the relationship between asthma, body mass index (BMI) and aerobic performance, as indicated by a shuttle test. METHODS: 20,577 participants (10,413 boys) from the SportsLinx serial cross-sectional study participated. Parental reports of asthma status and home postcode data were gathered from consent forms. Stature, sitting stature and body mass were measured and BMI, somatic maturity and indices of multiple deprivation scores (IMD) were derived. Performance on the 20 m multi-stage shuttle runs test (20mSRT) was used to estimate cardiorespiratory fitness (CRF). RESULTS: Asthma [F (1, 17,015) = 82.26, P < 0.01] and gender [F (1, 17,015) = 678.491, P < 0.001] significantly influenced 20mSRT. The addition of BMI, maturity and IMD to the model did not alter these significant effects. There was a significant interaction between 20mSRT and BMI [F (1, 16,723) = 132.80, P < 0.01], with a significant decrease in 20mSRT from the 50th BMI percentile upwards [t (16,699) = 36.88, P < 0.01]. Binary logistic regression revealed gender and 20mSRT to be significant predictors of asthma occurrence; BMI SDS just reached significance whilst maturity and IMD were not significant contributors to the model. CONCLUSIONS: This study demonstrates the negative influences of low CRF and high BMI on the risk of asthma occurrence in pre-pubertal children. Furthermore, it highlights the significant influence of BMI on CRF, revealing these effects to be manifest considerably below those BMI percentiles conventionally associated with being overweight or obese. PMID- 24213887 TI - Effectiveness of non-CO2 greenhouse gas emission reduction technologies. AB - Non-CO2 greenhouse gases, such as methane and nitrous oxide, can make a relevant contribution to the enhanced greenhouse effect, and hence emission reduction is desirable. In emission reduction inventories, both the magnitude of the emission reduction as well as the specific emission reduction costs should be determined. The current knowledge of the potential for and costs of reducing these emissions is still limited. Taking this into account, the following results can be obtained. Methane emissions can be considerably reduced from underground coal mining, oil production, natural gas operations, landfilling of waste, and wastewater treatment. Also emissions from enteric fermentation and animal manure can be reduced substantially. The total technical potential for methane emission reduction (given the present activity level) is estimated to be about one third. The economic potential, having net negative emission reduction costs, is estimated to be about half of this value. These reductions can be attained over a period of 10 - 20 years. The technical potential for the reduction of nitrous oxide emissions is currently estimated to be less than 10% Apart from the possibility of implementing existing techniques, there seems to be considerable room for developing techniques for more far-reaching emission reductions both for methane and nitrous oxide. PMID- 24213888 TI - National GHG inventories: Recent developments under the IPCC/OECD Joint Programme. AB - This paper summarises key results of the Joint IPCC/OECD Programme, in particular the draft IPCC Guidelines for National GHG Inventories to be released in January 1994. The focus is on how these results are likely to improve the availability and the quality of national inventories of anthropogenic GHG emission sources and removals by sinks. The IPCC/OECD has already received nearly 50 inventories from 35 countries. Most of the data are for 1988, but some reports cover 1989 and 1990. In addition to CO2, many of these inventories include CH4, N2O, NOx, CO, and NMVOC. Detailed analyses of these inventories have provided valuable insights about the strengths and weaknesses of the national inventories, differences in approach to estimation, reporting, available methods and data. These results in turn, have facilitated the development of the draft Guidelines, most notably the proposed reporting system, and also on estimation methods for the different anthropogenic sources and sinks of GHG. The paper previews key aspects of the draft Guidelines for non-CO2 GHG. Experts are urged to actively participate in the IPCC/OECD Programme to continue to improve inventory methods and overall the Guidelines. PMID- 24213889 TI - The African experience with the IPCC methodology for estimating greenhouse gas emissions. AB - In order to arrive at transparent and comparable inventories, the IPCC, in cooperation with the OECD, is currently developing a common methodology and reporting guidelines for the estimation of anthropogenic greenhouse gas emissions. To gain experience with the IPCC methodology, inventories are currently being carried out in various countries. This paper describes the African experience regarding emission inventories and preliminary results of the studies. It focuses on several important sources of non-CO2 greenhouse gas emissions in Africa: biomass burning; rice cultivation; and animals. PMID- 24213890 TI - Reporting emissions of greenhouse gases in Canada. AB - Non-carbon dioxide greenhouse gases are considered in "Canada's National Report on Climate Change: Actions to Meet Commitments Under the United Nations Framework Convention on Climate Change". By including all major greenhouse gases and their anthropogenic sources and sinks using best available science, the Report provides a practical illustration of the "comprehensive approach" policy to implementing the Convention's requirements. In addition to carbon dioxide emissions from fossil fuel combustion, the Report includes information on other sources and sinks for carbon dioxide, and for methane and nitrous oxide. Other gases considered include polyflourocarbons, hydroflourocarbons, and the primary tropospheric ozone precursors, nitrogen oxides and volatile organic compounds. Current Global Warming Potential indices are used to compare and integrate the best estimates of climate change impacts of the major greenhouse gases. The presentation of emission data is intended to be transparent and comparable. The relative quality of the data for various gases and sources is indicated. The existence of environmental, economic, and other benefits to limiting emissions of all greenhouse gases, in addition to carbon dioxide, should be recognized. Continuing assessments and actions on non-carbon dioxide greenhouse gas emissions, both nationally and internationally, are suggested. PMID- 24213891 TI - Non-CO2 gaseous emissions from upstream oil and gas operations in Nigeria. AB - The Nigerian crude oil is formed in association with natural gas. The associated gas has mostly been flared in the process of crude oil exploitation. Current estimates are that approximately 70% of produced natural gas is flared. Carbon monoxide, volatile organic compounds and nitrogen oxides emissions from oil and gas exploitation activities are presented for major combustion activities: gas flares and power generation at oil fields for oil and gas gathering systems. The emissions rates and combustion efficiency for a newly tested modified flaring system with enhanced air supply and liquid aspiration system for the atomization of the condensate phases of the flared gas was found to be capable of improving combustion efficiency by 20% or more in comparison with the conventional flare type currently in vogue. Flare emissions for CO and NOx are an order of magnitude higher than other sources in the oil and gas sector. PMID- 24213892 TI - Global methane emissions from the world coal industry. AB - The Coal Industry Advisory Board (CIAB) of the International Energy Agency (IEA) estimated the total methane emissions from worldwide mining, treatment and storage of coal to be approximately 25 million tonnes/year for 1990. Slightly more than one million tonnes of methane are utilized by the industry. Thus, the net annual discharge to the atmosphere is 24 million tonnes. Methane emissions data were available for the U.S., the U.K., former U.S.S.R., Australia, China, Germany, Poland and Czechoslovakia. Methane emissions for India and S. Africa were estimated from a linear correlation between the average depth of mining and specific methane emissions derived from the available data for the eight countries. These ten largest coal producing countries represented nearly 90% of world coal production in 1990. Total methane emissions for the world coal industry were calculated by prorating the methane emissions from these ten countries in proportion to coal production.The reported values represent the best international data available at present. The net total emissions of 24 million tonnes/year are substantially less than some previously reported indirect estimations and constitute only 4 to 6% of the global methane emissions. PMID- 24213893 TI - Emission database for global atmospheric research (Edgar). AB - Atmospheric chemistry and climate modellers require gridded global emissions data as input into their models. To meet this urgent need a global emissions source database called EDGAR is being developed by TNO and RIVM to estimate for 1990, on a regional and on a grid basis, annual emissions of greenhouse gases (CO2, CH4, N2O, CO, NOx, non-methane VOC, SOx), of NH3, and of ozone depleting compounds (halocarbons) from all known sources. The aim is to establish at due levels of spatial, temporal and source aggregation the emissions from both anthropogenic and biogenic sources: a complete set of data required to estimate the total source strength of the various gases with a 1*1 degrees resolution (altitude resolution of 1 km) and a temporal resolution of a month, supplemented by diurnal variation, as agreed upon in the Global Emissions Inventory Activity (GEIA) of the International Atmospheric Chemistry Programme (IGAC). In this way EDGAR will meet the requirements of present and future developments in the field of atmospheric modelling. The data comprise demographic data, social and economic factors, land use distributions and emission factors (with due emphasis on the uncertainty). As understanding in this field is still changing, due attention is paid to flexibility regarding the disaggregation of sources, spatial and temporal resolution and species. The objective and methodology chosen for the construction of the database and the structural design of the database system are presented, as well as the type and sources of data and the approach used for data collection. As an example, the construction of the N2O inventory is discussed. PMID- 24213894 TI - Anthropogenic emissions of methane and nitrous oxide in the Federal Republic of Germany. AB - The anthropogenic emission sources of methane (CH4) and nitrous oxide (N2O) in the Federal Republic of Germany were investigated. The object of the recently completed first phase of this research project was to summarize the present knowledge about the emission sources, make a first rough estimate of the emissions, identify the need for further research in the field, and - as far as possible - discuss the existing possibilities to reduce emissions. The main CH4 emission sources identified are the landfills, stock farming and pit mining, the main N2O sources are agriculture (including a minor contribution from animal wastes) and the production of adipic acid, the latter possibly being reducible by means of a new catalytic process. The total anthropogenic emissions of CH4 from Germany are estimated at 5.4 - 7.7 million tonnes per year, contributing a share of roughly 2 % to the world-wide anthropogenic emissions (350 million t/a). Those of N2O are estimated at 200 000 - 280 000 tonnes per year (world-wide 1.4 - 6.5 million t/a). PMID- 24213895 TI - Emission inventory for Nigeria with CAREAIR. AB - CAREAIR is the abbreviation for "Computer aided Analysis of Reduction strategies for Emissions and ambient AIR pollution". It is a modelling-system for air pollution analyses including a flexible emission model developed at the IER. The PC-based version of the system is especially designed for applications in so called 3rd-world countries, but in fact it can be used for any country. A modeling database for many emission relevant processes and related emission factors is part of it. This paper first gives a short overview on the capabilities of CAREAIR and secondly presents part of the emission inventory for Nigeria, which has been elaborated using CAREAIR during a cooperation between the University of Stuttgart (FRG) and the Obafemi Awolowo University of Ile-Ife (Nigeria). In particular estimates of the yearly emissions of total Hydrocarbons (VOC = Volatile Organic Compounds), divided into CH4 (Methane) and NMVOC (Non Methane-VOC), NOx (Nitrogen Oxides), N2O (Nitrous Oxide), CO2 (Carbon Dioxide) and CO (Carbon Monoxide) emissions in Nigeria 1989 are given. PMID- 24213896 TI - Consumption of methane by soils. AB - Measurements of the methane flux and methane concentration profiles in soil air are presented. The flux of methane from the soil is calculated by two methods: a) Direct by placing a static open chamber at the soil surface. b) Indirect, using the (222)Rn concentrations profile and the (222)Rn flux in the soil surface in parallel with the methane concentration ((222)Rn calibrated fluxes). The methane flux has been determined in two kinds of soils (sandy and loamy) in the surroundings of Malaga (SPAIN). The directly measured methane fluxes at all investigated sites is higher than methane fluxes derived from "Rn calibrated fluxes". Atmospheric methane is consumed by soils, mean direct flux to the atmosphere were - 0.33 g m(-2)yr-1. The direct methane flux is the same within the measuring error in sandy and loamy soils. The influence of the soil parameters on the methane flux indicates that microbial decomposition of methane is primarily controlled by the transport of methane. PMID- 24213897 TI - CH4 and CO emissions from rice straw burning in South East Asia. AB - Atmospheric samples collected during rice straw burning at four different locations in Viet-Nam during the dry (March 1992, February 1993) and wet season (August 1992) were analysed for CO2, CO, and CH4. The emission ratios relative to CO2 for CO and CH4 for rice straw burning during the dry season were comparable to those observed on samples collected during burning of savanna in Africa or forest in the USA. During the wet season, however the emission ratios for CO and CH4 relative to CO2 were 3 to 10 times higher. With these emission ratios and estimates of rice production from Southeastern Asia, we estimated that burning of rice straw emits annually about 2.2 Tmol of CO (26 TgC) and 0.2 Tmol of CH4 (2.4 TgC) to the atmosphere. Taking into account these new results, CO and CH4 fluxes from biomass burning could be reevaluated by 5-21% and 5-24%, respectively, in respect with previous estimates of these gas emissions from all biomass burning activities. PMID- 24213898 TI - Methane in ocean waters: Concentration and carbon isotope variability at East Pacific Rise and in the Arabian Sea. AB - Methane concentrations and stable carbon isotope ratios of water samples from the East Pacific Rise (EPR) at 21 degrees S and the Arabian Sea (24 degrees N, 65 degrees E) have been determined. EPR surface water is in equilibrium (ca. 50 nl/L and -500/00100nl/L and -300/0050 nmol kg(-1)). In the controls of soil 1 and soil 2, which showed very low NO emissions ratios of <1 were observed. The N2O/NO ratios varied between 5-20 when NO emissions were considerable (>50 nmol kg(-1)). Soil 3 and 4 gave lower N2O/NO ratios than soil 1 and 2. In the controls of soil 1 and soil 2, at low NO emissions, N2O/NO ratios of >300 were observed. Soil 3 and 4 gave higher NO/NO2 and lower N2O/NO ratios than soil 1 and 2. PMID- 24213905 TI - Inspection of non-CO2 greenhouse gases from emission sources and in ambient air by Fourier-transform-infrared-spectrometry: Measurements with FTIS-MAPS. AB - Infrared spectrometry is a versatile basis to analyse greenhouse gases in the atmosphere. A multicomponent air pollution software (MAPS) was developed for retrieval of gas concentrations from radiation emission as well as absorption measurements. Concentrations of CO, CH4, N2O, and H2O as well as CO2, NO, NO2, NH3, SO2, HCl, HCHO, and the temperature of warm gases are determined on-line. The analyses of greenhouse gases in gaseous emission sources and in ambient air are performed by a mobile remote sensing system using the double-pendulum interferometer K300 of the Munich company Kayser-Threde. Passive radiation measurements are performed to retrieve CO, N2O, and H2O as well as CO2, NO, SO2, and HCl concentrations in smoke stack effluents of thermal power plants and municipal incinerators and CO and H2O as well as CO2 and NO in exhausts of aircraft engines. Open-path radiation measurements are used to determine greenhouse gas concentrations at different ambient air conditions and greenhouse gas emission rates of diffusive sources as garbage deposits, open coal mining, stock farming together with additional compounds (e.g. NH3), and from road traffic together with HCHO. Some results of measurements are shown. A future task is the verification of emission cadastres by these inspection measurements. PMID- 24213906 TI - Determination of European methane emissions, using concentration and isotope measurements. AB - The determination of methane emissions on a regional scale is needed in order to reduce some of the uncertainties in the global methane budget. Our measurements of the concentration and the Carbon-13 isotope composition (delta(13)C) of atmospheric methane are, combined with trajectories, used to get insight in the type and size of the methane emissions of a large area. PMID- 24213907 TI - Monitoring of the atmospheric burdens of CH4, N 2O, CO, CHCIF 2 and CF 2Cl 2 above Central Europe during the last decade. AB - Based on high spectral resolution infrared solar observations made at the International Scientific Station of the Jungfraujoch, Switzerland, total vertical column abundances of 18 atmospheric gases have been monitored routinely since 1984. The observed temporal evolutions in the columns of CH4, N2O, CO, CHClF2 (HCFC-22) and CF2Cl2 (CFC-12) are reported here as typical examples of this monitoring effort which is conducted within the frame of "Global Change" and "Network for the Detection of Stratospheric Change" programs. PMID- 24213908 TI - Polar volatile organic compounds (VOC) of natural origin as precursors of ozone. AB - HRGC-MS determinations carried out on samples collected in urban, suburban, rural, forest and remote areas suggest that several other classes of non-methane VOC than isoprene and monoterpene hydrocarbons can be emitted by plants. Because of their high photochemical reactivity, they can contribute to tropospheric ozone production which, in turn, can cause climate changes through radiative forcing. PMID- 24213909 TI - Measurements of CFCs in Antarctica. PMID- 24213911 TI - Conference statement. PMID- 24213910 TI - Preface. PMID- 24213912 TI - A model design for the labyrinthine membranes in mammals. AB - OBJECTIVES/HYPOTHESIS: A model of the labyrinthine membranes in mammals may be useful in the study of conditions that involve membrane stress and deformation such as Meniere's disease and diving injuries. STUDY DESIGN: Conceptual design of a model of the labyrinthine membranes in mammals. METHODS: The model is constructed by emulating each of the several chambers of the membranous labyrinth and their connections with mathematically defined geometric shapes. RESULTS: The model design uses a torus to emulate each semicircular canal, prolate spheroids for each ampulla, cylinders for the crus commune and utricle, an oblate spheroid for the saccule, hyperboloids of revolution for junctional zones, and a spiral torus for the cochlea membranes. CONCLUSIONS: A complete model of the labyrinthine membranes has been designed that can serve as a platform for stress analysis when numerical dimensions are available for any particular species including man. LEVEL OF EVIDENCE: NA. PMID- 24213913 TI - Adequacy of an evidence-based treatment guideline for complicated urinary tract infections in the Netherlands and the effectiveness of guideline adherence. AB - Guideline recommendations on empirical antibiotic treatment are based on the literature, expert opinion, expected pathogens and resistance data, but their adequacy in the real-life setting is often unknown. We investigated the adequacy of the Dutch evidence-based guideline-recommended treatment options for patients with complicated urinary tract infections (UTIs) 2 years after guideline publication and, additionally, the adequacy of actually prescribed empirical therapy for patients treated with guideline-adherent versus non-guideline adherent therapy. A retrospective, observational multicentre study in the Netherlands included 810 patients with a complicated UTI without special conditions and 174 with a urinary catheter. The susceptibility patterns of cultured uropathogens were compared with guideline-recommended treatment options, which included specific recommendations for patients with a catheter, and with actually prescribed empirical therapy. We considered inadequate coverage rates below 10% as acceptable. Of the recommended regimens for patients with a UTI without other conditions, only the guideline-recommended combination of amoxicillin-gentamicin was acceptable (inadequate coverage rate 6%). For patients with a catheter, inadequate coverage rates of recommended regimens ranged from 3 to 24%. In patients with a UTI without other conditions, actually prescribed guideline-adherent therapy resulted in less broad-spectrum but not in less adequate therapy; in patients with a catheter, actually prescribed guideline adherent therapy resulted in a higher coverage rate than those prescribed non guideline-adherent therapy. Due to the continuously changing resistance rates and differences between the epidemiologies of uropathogens assumed in the guideline and those in real life, regular real-life assessments of recommended treatment options are necessary. Guideline adherence seems to be effective for increasing coverage rates without prescribing unnecessarily broad regimens. PMID- 24213914 TI - HIV-1 coreceptor switch during 2 years of structured treatment interruptions. AB - The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanita-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20%) was used for data interpretation. At baseline, 9/12 subjects (75.0%) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5-X4, one X4-R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism. PMID- 24213915 TI - Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways. AB - The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88(-) mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88(-) mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function. PMID- 24213916 TI - F-actin scaffold stabilizes lamellar bodies during surfactant secretion. AB - Alveolar type 2 (AT2) cells secrete surfactant that forms a protective layer on the lung's alveolar epithelium. Vesicles called lamellar bodies (LBs) store surfactant. Failure of surfactant secretion, which causes severe lung disease, relates to the manner in which LBs undergo exocytosis during the secretion. However, the dynamics of LBs during the secretion process are not known in intact alveoli. Here, we addressed this question through real-time confocal microscopy of single AT2 cells in live alveoli of mouse lungs. Using a combination of phospholipid and aqueous fluorophores that localize to LBs, we induced surfactant secretion by transiently hyperinflating the lung, and we quantified the secretion in terms of loss of bulk LB fluorescence. In addition, we quantified inter-LB phospholipid flow through determinations of fluorescence recovery after photobleaching. Furthermore, we determined the role of F-actin in surfactant secretion through expression of the fluorescent F-actin probe Lifeact. Our findings indicate that, in AT2 cells in situ, LBs are held in an F-actin scaffold. Although F-actin transiently decreases during surfactant secretion, the LBs remain stationary, forming a chain of vesicles connected by intervesicular channels that convey surfactant to the secretion site on the plasma membrane. This is the first instance of a secretory process in which the secretory vesicles are immobile, but form a conduit for the secretory material. PMID- 24213917 TI - Recent advances in late lung development and the pathogenesis of bronchopulmonary dysplasia. AB - In contrast to early lung development, a process exemplified by the branching of the developing airways, the later development of the immature lung remains very poorly understood. A key event in late lung development is secondary septation, in which secondary septa arise from primary septa, creating a greater number of alveoli of a smaller size, which dramatically expands the surface area over which gas exchange can take place. Secondary septation, together with architectural changes to the vascular structure of the lung that minimize the distance between the inspired air and the blood, are the objectives of late lung development. The process of late lung development is disturbed in bronchopulmonary dysplasia (BPD), a disease of prematurely born infants in which the structural development of the alveoli is blunted as a consequence of inflammation, volutrauma, and oxygen toxicity. This review aims to highlight notable recent developments in our understanding of late lung development and the pathogenesis of BPD. PMID- 24213918 TI - Angiostatin inhibits acute lung injury in a mouse model. AB - Acute lung injury is marked by profound influx of activated neutrophils, which have delayed apoptosis, along with fluid accumulation that impairs lung function and causes high mortality. Inflammatory and antimicrobial molecules, such as reactive oxygen species from activated neutrophils with prolonged lifespan, cause tissue damage and contribute to lung dysfunction. Angiostatin, an endogenous antiangiogenic molecule, is expressed in the lavage fluid of patients with acute respiratory distress syndrome and modifies neutrophil infiltration in a mouse model of peritonitis. Our aim was to investigate the therapeutic role of angiostatin in acute lung injury. We analyzed bronchoalveolar lavage and lung tissues from C57BL/6 mouse model of Escherichia coli LPS-induced acute lung injury to assess the effects of angiostatin treatment. Subcutaneous angiostatin administered at 5 h after LPS treatment reduces histological signs of inflammation, protein accumulation, lung Gr1+ neutrophils, myeloperoxidase activity, and expression of phosphorylated p38 MAPK in lung tissues and peripheral blood neutrophils, while increasing the number of apoptotic cells in the lungs without affecting the levels of macrophage inflammatory protein-1 alpha, IL-1beta, keratinocyte chemoattractant, and monocyte chemoattractant protein-1 in lavage and lung homogenates at 9 and 24 h after LPS treatment. In contrast, angiostatin administered intravenously 5 h after LPS treatment did not reduce histological sign of inflammation, BAL cell recruitment, and protein concentration at 9 h of LPS treatment. We conclude that angiostatin administered subcutaneously after LPS challenge inhibits acute lung inflammation up to 24 h after LPS treatment. PMID- 24213919 TI - Preclinical evaluation of human secretoglobin 3A2 in mouse models of lung development and fibrosis. AB - Secretoglobin (SCGB) 3A2 is a member of the SCGB gene superfamily of small secreted proteins, predominantly expressed in lung airways. We hypothesize that human SCGB3A2 may exhibit anti-inflammatory, growth factor, and antifibrotic activities and be of clinical utility. Recombinant human SCGB3A2 was expressed, purified, and biochemically characterized as a first step to its development as a therapeutic agent in clinical settings. Human SCGB3A2, as well as mouse SCGB3A2, readily formed a dimer in solution and exhibited novel phospholipase A2 inhibitory activity. This is the first demonstration of any quantitative biochemical measurement for the evaluation of SCGB3A2 protein. In the mouse as an experimental animal, human SCGB3A2 exhibited growth factor activity by promoting embryonic lung development in both ex vivo and in vivo systems and antifibrotic activity in the bleomycin-induced lung fibrosis model. The results suggested that human SCGB3A2 can function as a growth factor and an antifibrotic agent in humans. When SCGB3A2 was administered to pregnant female mice through the tail vein, the protein was detected in the dam's serum and lung, as well as the placenta, amniotic fluids, and embryonic lungs at 10 min postadministration, suggesting that SCGB3A2 readily crosses the placenta. The results warrant further development of recombinant SCGB3A2 as a therapeutic agent in treating patients suffering from lung diseases or preterm infants with respiratory distress. PMID- 24213920 TI - Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection. AB - The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic landscape of bronchoalveolar lavage fluid (BALF) in patients with HIV would provide insights into how this virus alters the lung milieu and contributes to pathogenesis of HIV-related lung diseases. BALF was obtained from five HIV negative (HIV(-)) and six asymptomatic HIV-positive (HIV(+)) subjects not on antiretroviral therapy. Each sample underwent shotgun proteomic analysis based on HPLC-tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation to identify overlapping and distinct pathways enriched between the BALF proteome of HIV(+) and HIV(-) subjects. We identified a total of 318 unique proteins in BALF of HIV( ) and HIV(+) subjects. Of these, 87 were differentially up- or downregulated between the two groups. Many of these differentially expressed proteins are known to interact with key HIV proteins. Functional analysis of differentially regulated proteins implicated downregulation of immune responses in lungs of HIV(+) patients. Combining shotgun proteomic analysis with computational methods demonstrated that the BALF proteome is significantly altered during HIV infection. We found that immunity-related pathways are underrepresented in HIV(+) patients. These findings implicate mechanisms whereby HIV invokes local immunosuppression in the lung and increases the susceptibility of HIV(+) patients to develop a wide range of infectious and noninfectious pulmonary diseases. PMID- 24213922 TI - Impact of concomitant carcinoma in situ on upstaging and outcome following radical cystectomy for bladder cancer. AB - PURPOSE: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. METHODS: We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. RESULTS: In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. CONCLUSION: These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy. PMID- 24213921 TI - Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons. AB - The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure. PMID- 24213923 TI - Effects of incapacitant spray deployed in the restraint and arrest of detainees in the Metropolitan Police Service area, London, UK: a prospective study. AB - PURPOSE: In the United Kingdom (UK) police restraint and control of detainees is undertaken by assorted means. Two types of incapacitant spray (IS) are approved by the UK Home Office for use: CS (o-chlorobenzylidine malononitrile, dissolved in an organic solvent--methyl iso-butyl ketone and pelargonic acid vanillyamide (PAVA). The aim of this study was to document the effects of incapacitant sprays, by symptom assessment and medical examination, within a few hours of deployment. METHODS: A detailed proforma was produced to explore the nature of the arrest, the nature of exposure to the incapacitant spray, the type of incapacitant spray, the symptoms experienced and the medical findings. RESULTS: 99 proformas were completed. 74 % were completed by detainees and 26 % were completed by police officers. 88 % were exposed to CS spray, the remainder to PAVA spray. The mean time of assessment after exposure was 2.8 +/- 2.33 h (mean +/- SD). The most frequent sites of IS contact were the face and scalp (n = 78), and exposure to the left and right eyes (n = 32). The most common symptoms were: painful eyes (n = 68); red eyes (n = 58); runny nose (n = 59); lacrimation (n = 55); nasal discomfort (n = 52); skin irritation (n = 49); and skin burning (n = 45). The most common medical findings were: conjunctival erythema (n = 34); skin erythema (n = 21); and rhinorrhea (n = 20). CONCLUSIONS: Symptoms and signs of exposure to IS lasted longer than was expected (a mean of 2.8 h). Approximately 30 % of those exposed had ocular effects and 20 % had skin effects. The findings of this study will enable the guidelines on the expected effects and duration of symptoms resulting from exposure to incapacitant sprays to be reviewed and suggestions for their management to be refined. PMID- 24213924 TI - Physical activity and risk of endometrial adenocarcinoma in the Nurses' Health Study. AB - Studies suggest that greater physical activity may reduce endometrial cancer risk. However, the role of the timing, duration and intensity of activity is unclear. We therefore examined recent and past recreational activities in relation to incident endometrial adenocarcinoma, and compared the importance of total and moderate- or vigorous-intensity activities as well as walking. We analyzed data from 71,570 women in the Nurses' Health Study, a prospective cohort that assessed activity in 1986, with updates every 2-4 years. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). During follow-up from 1986 to 2008 (1.2 million person-years), 777 invasive endometrial adenocarcinoma cases were documented. In multivariable models, compared with <3 MET-hr/week (<1 hr/week walking), women engaged in moderate (9 to <18 MET-hr/week: RR = 0.61, 95% CI: 0.48-0.78) or high (>=27 MET hr/week: RR = 0.73, 95% CI: 0.58-0.92) amounts of recent total recreational activity were at reduced risk (p-trend = 0.001). Past total activity was not associated with risk. Greater recent moderate- or vigorous-intensity activity was associated with reduced risk (>=4 vs. 0 hr/week: RR = 0.65, 95% CI: 0.47-0.88, p trend = 0.002). Among women who did not perform any vigorous activity, recent walking was associated with reduced risk (>=3 vs. <0.5 hr/week: RR = 0.65, 95% CI: 0.45-0.93, p-trend = 0.01), and faster walking pace was independently associated with risk reduction. After additional adjustment for body mass index, all associations were statistically non-significant. Greater recent physical activity, including activity of moderate duration and intensity such as walking, may reduce endometrial adenocarcinoma risk. This relation is largely mediated or confounded by body mass index. PMID- 24213925 TI - Molecular cloning and expression of a C-type lectin gene from Venerupis philippinarum. AB - C-type lectins have been demonstrated to play important roles in invertebrate innate immunity by mediating the recognition of pathogens and clearing the micro invaders. In the present study, a C-type lectin gene (denoted as VpCTL) was identified from Venerupis philippinarum by expressed sequence tag and rapid amplification of cDNA ends approaches. The full-length cDNA of VpCTL consists of 904 nucleotides with an open-reading frame of 456 bp encoding a peptide of 151 amino acids. The deduced amino acid sequence of VpCTL shared high similarity with C-type lectins from other species. The C-type lectin domain and the characteristic EPN and WND motifs were found in VpCTL. The VpCTL mRNA was dominantly expressed in the haemocytes of the V. philippinarum. After Listonella anguillarum challenge, the temporal expression of VpCTL mRNA in haemocytes was increased by 97- and 84-fold at 48 and 96 h, respectively. With high expression level in haemocytes and hepatopancreas, and the up-regulated expression in haemocytes indicted that VpCTL was perhaps involved in the immune responses to L. anguillarum challenge. PMID- 24213926 TI - Sequence analysis of bovine C/EBPdelta gene and its adipogenic effects on fibroblasts. AB - CCAAT/enhancer binding protein delta (C/EBPdelta), an important transcriptional factor, regulates cell growth, differentiation and adipogenesis in humans and mice. However, we lack of directive information on the effects of C/EBPdelta gene in bovine cells. In the present study, we cloned the CDS areas of bovine C/EBPdelta gene and predicted its sequence characteristics. Moreover, we constructed the recombinant adenovirus plasmids of bovine C/EBPdelta gene and harvested the subsequent adenoviruses to infect bovine primary fibroblasts. Oil Red O staining results showed lipid droplets accumulated gradually in the adenoviruses treated fibroblasts. Time course real-time PCR results indicated that over-expression of exogenous C/EBPdelta regulated the mRNA expression levels of some key adipogenic genes, herein, activated the C/EBPalpha expression, increased lipoprotein lipase and fatty acid binding protein 4 mRNA expression levels, whereas inhibited leptin receptor gene. In conclusion, the present study demonstrates that the elevated C/EBPdelta can induce the adipogenesis in the fibroblasts of cattle. PMID- 24213927 TI - Haplotype analysis of RECQL5 gene and laryngeal cancer. AB - RECQL is a DNA helicase involved in DNA mismatch repair. Previous studies indicated that the RECQL gene mutation was associated with human cancers. In the present study, we investigated the association between polymorphisms of RECQL gene and laryngeal cancer in a Chinese population. Four polymorphisms of the RECQL5 gene (rs820186, rs820196, rs820200, and rs4789223) were genotyped by the TaqMan method in 275 patients with larynx cancer and 300 age- and sex-matched non cancer controls. We found that rs820196 polymorphism of RECQL5 was associated with larynx cancer, the CC genotype (16.4% vs 9.3%, P = 0.013) and C allele (42% vs 34.2%, P = 0.006) was common in larynx cancer patients than in the control subjects, respectively. Haplotype analysis showed that GCGA (OR = 18.955, 95% confidence interval (CI) 9.479 ~ 37.905; P < 0.001) and GTTG (OR = 1.684; 95% CI 1.327 ~ 2.137; P < 0.001) were associated with increased risk for larynx cancer. However, ACGA (OR = 0.605; 95% CI 0.430 ~ 0.852; P = 0.003), GCGG (OR = 0.636; 95% CI 0.411 ~ 0.982; P = 0.039), and GTGG (OR = 0.194; 95% CI 0.104 ~ 0.361; P < 0.001) were associated with decreased risk for larynx cancer. The present study indicated that RECQL5 genetic polymorphism and haplotypes were associated with larynx cancer in a Chinese population. PMID- 24213928 TI - AU-binding factor 1 expression was correlated with metadherin expression and progression of hepatocellular carcinoma. AB - RNA-binding factor 1 (AUF1) was found to be up-regulated in numerous tumors compared with untransformed tissues. Furthermore, it has been identified to regulate mRNAs en masse in hepatocellular carcinoma (HCC). Metadherin (MTDH) as a novel oncogene also promotes tumor progression and metastasis in HCC. Our study aimed to investigate the correlation between AUF1 and MTDH expressions by immunochemistry in 146 HCC patients from Heilongjiang region. AUF1 expression in HCC tumors was higher than that in the matched normal liver tissues. Particularly, AUF1 overexpression was closely associated with tumor size (P < 0.022), TNM stage (P < 0.003), hepatitis B surface antigen status, and AFP serum levels (P < 0.05). Furthermore, AUF1 overexpression led to poor outcome during 5 year follow-up (P < 0.001). Additionally, AUF1 and MTDH expressions were correlated with each other. Our findings suggest that the AUF1 gene may play an important role in HCC progression and be a novel biomarker in the future. PMID- 24213929 TI - On the continuity of thought and the representation of knowledge: Electrophysiological and behavioral time-course measures reveal levels of structure in semantic memory. AB - Time-course studies of semantic verification are reviewed, discussed, and reinterpreted with the aim of drawing general theoretical conclusions about semantic memory structure. These reaction time, speed-accuracy tradeoff, speed accuracy decomposition, and event-related (brain) potential (ERP) studies suggest that semantic memory is structured on at least three levels. In particular, specific models of the intermediate (macrostructural) level are discussed and compared. ERP investigations of this level suggest that context-independent and context-dependent types of semantic information are potentially isolable and analyzable. PMID- 24213930 TI - Constraints on theories of cognitive aging. AB - There is currently little consensus regarding what must be explained by theories of cognitive aging. In the present article, four empirical generalizations that seem to imply certain constraints in theorizing are identified. These generalizations, and their possible implications or constraints, are that (1) age related differences are found in a wide range of cognitive variables, implying that either a large number of specific factors or a small number of general factors must be contributing to the age-related differences; (2) the age-related influences on different cognitive variables are not independent, and unique age related influences appear to be few in number and small in magnitude, implying that some fairly general factors need to be postulated to account for the shared age-related influences; (3) only a small proportion of distinct age-related variance occurs late in practice and at long presentation durations, implying that adequate explanations must include factors operating when the individuals are just beginning to perform the task and when the stimuli can first be registered; and (4) measures of how quickly very simple cognitive tasks can be performed share considerable age-related variance with many cognitive variables, implying that factors related to simple processing efficiency need to be incorporated into the explanations. PMID- 24213931 TI - Odor memory: Review and analysis. AB - We critically review the cognitive literature on olfactory memory and identify the similarities and differences between odor memory and visual-verbal memory. We then analyze this literature using criteria from a multiple memory systems approach to determine whether olfactory memory can be considered to be a separate memory system. We conclude that olfactory memory has a variety of important distinguishing characteristics, but that more data are needed to confer this distinction. We suggest methods for the study of olfactory memory that should make a resolution on the separate memory system hypothesis possible while simultaneously advancing a synthetic understanding of olfaction and cognition. PMID- 24213933 TI - History of the Psychonomic Society II: The journal publishing program. AB - The possibility of a Psychonomic Society journal publishing program dates back to the very founding of the Society in 1959. The program was initiated by Clifford T. Morgan on his own, however, with the publication ofPsychonomic Science in 1964, followed byPsychonomic Monograph Supplements andPerception & Psychophysics within the next 2 years. In 1967, Morgan gave the journals to the Psychonomic Society, which has controlled them ever since. The structure of the journal program and the means of producing the journals have evolved since then, so that today the Psychonomic Society publishes six prominent journals in experimental psychology, all of them produced in-house. PMID- 24213932 TI - The widespread influence of the Rescorla-Wagner model. AB - The theory of Pavlovian conditioning presented by Robert Rescorla and Allan Wagner in 1972 (the Rescorla-Wagner model) has been enormously important in animal learning research. It also has been applied in a variety of areas other than animal learning. We summarize the contribution of the Rescorla-Wagner model to research in verbal learning, social psychology, human category learning, human judgments of correlational relationships, transitive inference, color aftereffects, and physiological regulation. We conclude that there have been few models in experimental psychology as influential as the Rescorla-Wagner model. PMID- 24213934 TI - Signal probability effects on high-workload vigilance tasks. AB - Signal probability is an important influence on vigilance. Typically, higher signal probability is associated with higher hit rate, lower response criterion, and lower response:signal ratio. However, signal probability effects on demanding, high-workload vigilance tasks have not been investigated. It is believed that attentional resources become depleted during performance of such tasks, leading to perceptual sensitivity decrements. Forty subjects performed high- (.35) and low- (.10) probability versions of a demanding vigilance task. Results differed in two important respects from those previously obtained with less demanding tasks. First, the decrement in perceptual sensitivity over time was greater for the high-probability task. Second, there were no effects of signal probability on response criterion. Subjective workload was higher for the high-probability task. Implications of the data for resource-depletion and expectancy theories of vigilance are discussed. PMID- 24213935 TI - Priming impossible figures in the object decision test: The critical importance of perceived stimulus complexity. AB - Previous research showed that object decision priming was found for possible, but not impossible, three-dimensional objects (e.g., Schacter, Cooper, & Delaney, 1990; Schacter, Cooper, Delaney, Peterson, & Tharan, 1991). We tested those objects and found that the impossible objects were subjectively more complex than the possible objects. We then constructed two sets of possible and impossible objects-one set that was equated for complexity, and one set that differed- for use in the object decision test. The results showed that when impossible objects were high in complexity and possible objects were low in complexity, priming was found only for possible objects; when possible and impossible objects were equated at a moderate level of complexity, priming was observed for both object types. These findings indicate that perceived object complexity, more than object possibility-impossibility, determined priming in the object decision test. The demonstration of object decision priming for possible and impossible objects calls for a reformulation of the structural description system explanation. PMID- 24213936 TI - Searching for target letters in memory: Individual preferences and instructions for text representation. AB - Participants searched for target letters in a short passage held in memory. In Experiment 1, participants were divided into two groups on the basis of a retrospective report concerning the type of representation used to store the passage in memory, and in Experiment 2, participants were instructed concerning the form of memory representation to use. Only participants using a visual representation missed more targets in the wordthe than in other words. Participants instructed to form a visual representation also made fewer content word or phrase substitutions when learning the passage than did participants instructed to form an auditory representation. These findings show that choice of memory representation is flexible and that the representation used influences what can be retrieved from memory. PMID- 24213937 TI - Spatial contiguity facilitates Pavlovian conditioning. AB - The spatial contiguity between Pavlovian conditioned and unconditioned stimuli was examined using a chamber designed to prevent the usual confounding with delay of reinforcement. Eight ring doves were autoshaped in this apparatus. For half of the trials, a conditioned stimulus (CS) was presented 11 cm from the unconditioned stimulus (US); for the other trials, another CS was presented 74 cm away. After extended training, the stimuli were presented in nonreinforced test trials at a common, intermediate (42 cm) position. The CS that had been nearer the US was approached more closely, indicating that higher spatial contiguity facilitates Pavlovian conditioning. This research was funded by a grant from the National Science and Engineering Research Council to B. R. Moore, who also assisted in designing the apparatus. Thanks are extended to Tracy Taylor, Billy Schmidt, and B. R. Moore for suffering through drafts of this manuscript and providing helpful insights to improve the writing. Thanks are also extended to Bob Barnet for help in clarifying this paper and inspiring some of the ideas for future research. PMID- 24213938 TI - Are attentional dwell times inconsistent with serial visual search? AB - Duncan, Ward, and Shapiro (1994) estimated that attention must remain focused on an object for several hundred milliseconds before being shifted to another object, and they referred to this period as theattentional dwell time. An important implication of these long estimates of the dwell time for models of visual search is that the search process must not involve an item-by-item serial scanning mechanism. If it did, then searching through an array of items would require enormous amounts of time, which-based on data from visual search experiments-it does not. The present report, however, provides evidence that the long estimates of attentional dwell time were caused, at least in part, by the use of masked targets. Implications of these variable estimates of the attentional dwell time for models of visual search are discussed. PMID- 24213939 TI - Repetition of previously novel melodies sometimes increases both remember and know responses in recognition memory. AB - Recognition memory for previously novel melodies was tested in three experiments in which subjects usedremember andknow responses to report experiences of recollection, or of familiarity in the absence of recollection, for each melody they recognized. Some of the melodies were taken from Polish folk songs and presented vocally, but without the words. Others were taken from obscure pieces of classical music, presented as single-line melodies. Prior to the test, the melodies were repeated for varying numbers of study trials. Repetition of the Polish melodies increased both remember and know responses, while repetition of classical melodies increased remember but not know responses. When subjects were instructed to report guesses, guess responses were inversely related to remember and know responses and there were more guesses to lures than to targets. These findings establish that remembering and knowing are fully independent functionally and, by the same token, they provide further evidence against the idea that response exclusivity causes increases in remembering to force decreases in knowing. The findings also suggest that simultaneous increases in remembering and knowing occurred because the Polish melodies came from a genre for which the subjects had relatively little previous experience. PMID- 24213940 TI - Reinforcer value may change within experimental sessions. AB - Large and systematic changes in response rates often occur within sessions during operant conditioning procedures. In the present experiment, we asked whether the value of the reinforcer that supports responding also changes within sessions. Pigeons pecked a key for mixed grain available throughout the session. Occasionally, wheat was also provided for pecking a second key. The ratio of the rates of responding for mixed grain and wheat, a frequently used measure of relative reinforcer value, changed significantly within sessions when mixed grain was provided at high, but not at low, rates. Habituation to the reinforcer provides the most likely explanation for these changes in reinforcer value. Eventually, habituation may provide a unified explanation for the within-session changes in behavior that occur when many species of subjects respond on a wide variety of tasks. PMID- 24213941 TI - The relationship between the number of presented stimuli and prospective duration estimates: The effect of concurrent task activity. AB - The attention/distraction models of prospective time estimation predict either a negative relationship or an independence between duration estimates and the number of stimulus events presented during the time period, but not a positive relationship. Two experiments examined this relationship under prospective conditions. Lists of words were presented during a 60-sec time period at either a fast or a slow rate. Subjects either passively viewed the words or actively responded by performing either a graphemic or a semantic classification task on each word. To measure subjective duration, the method of magnitude estimation was used in Experiment 1 and the method of reproduction was used in Experiment 2. Time estimates were independent of the number of presented words in the passive viewing condition, and negatively related in the classification task conditions. Furthermore, the two classification tasks had similar effects on time estimates. These findings are consistent with the attentional models of prospective timing, and they question the robustness of earlier findings of a positive relationship between time estimates of moderately long intervals and the number of presented stimuli under conditions of minimal processing of the interval events. PMID- 24213942 TI - Revisiting an old issue: Retroactive interference as a function of the degree of original and interpolated learning. AB - Prior research has generally shown that the greater the degree of original learning of a list, the greater the amount of retroactive interference that list suffers. In addition, greater learning of interpolated lists produces more retroactive interference. However, in prior research, the degree of learning has typically been confounded with the amount of retrieval practice on the list. Two free-recall experiments are reported in which subjects studied one original list and then 0, 1, 2, 3, or 4 interpolated lists. The degree of original and of interpolated learning was manipulated by varying exposure time. In Experiment 1, where the typical confounding of retrieval practice and degree of interpolated learning was present, greater interpolated learning induced greater retroactive interference, which is consistent with prior research. However, in Experiment 2, where the degree of interpolated learning was manipulated without concomitant variation in retrieval practice, retroactive interference was the same, whether the interpolated lists had been learned well or poorly. Therefore, greater interpolated learning does not increase the amount of retroactive interference. The results also show that the amount of retroactive interference does not depend on the degree of original learning, in agreement with other work on normal forgetting. PMID- 24213943 TI - Long-term benefits of seeding the knowledge base. AB - Exposure to numerical examples (seed facts) produced a substantial long-term reduction in domain-specific innumeracy. In particular, learning the populations of 24 seed countries improved accuracy of estimates of the populations of 75 untrained countries, both at the time of learning and 4 months later. Consistent with abstraction-based theories of learning and memory, the benefits of having been exposed to the seed facts were as large 4 months after the exposure as immediately after it, despite the specific populations of the seed countries having been forgotten during the interval. PMID- 24213944 TI - The long and winding road of molecular data in phylogenetic analysis. AB - The use of molecules and reactions as evidence, markers and/or traits for evolutionary processes has a history more than a century long. Molecules have been used in studies of intra-specific variation and studies of similarity among species that do not necessarily result in the analysis of phylogenetic relations. Promoters of the use of molecular data have sustained the need for quantification as the main argument to make use of them. Moreover, quantification has allowed intensive statistical analysis, as a condition and a product of increasing automation. All of these analyses are subject to the methodological anxiety characteristic of a community in search of objectivity (Suarez-Diaz and Anaya Munoz, Stud Hist Philos Biol Biomed Sci 39:451-458, 2008). It is in this context that scientists compared and evaluated protein and nucleic acid sequence data with other types of molecular data - including immunological, electrophoretic and hybridization data. This paper argues that by looking at long-term historical processes, such as the use of molecular evidence in evolutionary biology, we gain valuable insights into the history of science. In that sense, it accompanies a growing concern among historians for big-pictures of science that incorporate the fruitful historical research on local cases of the last decades. PMID- 24213945 TI - Micromolar copper modifies electrical properties and spontaneous discharges of nodose ganglion neurons in vitro. AB - Copper plays a key role in aerobic cell physiology mainly related to mitochondrial metabolism. This element is also present at higher than basal levels in some central nuclei and indeed, current evidence support copper's role as a neuromodulator in the central nervous system. More recent data indicate that copper may also affect peripheral neuronal activity, but so far, there are not detailed descriptions of what peripheral neuronal characteristics are targeted by copper. Here, we studied the effect of physiological concentration of CuCl2 (MUM range) on the activity of peripheral neurons using a preparation of nodose ganglion in vitro. By mean of conventional intracellular recordings passive and active electrical membrane properties were studied. Extracellular copper modified (in a redox-independent manner) the resting membrane potential and the input resistance of the nodose ganglion neurons, increasing the excitability in most of the tested neurons. These results suggest that Cu(2+) modulates the activity of nodose ganglion neurons and support nodose ganglion in vitro preparation as a simple model to study the subcellular mechanisms involved in the Cu(2+) effects on neuron electrical properties. PMID- 24213947 TI - Letter to the editor. PMID- 24213946 TI - Clubfoot care in low-income and middle-income countries: from clinical innovation to a public health program. AB - BACKGROUND: Clubfoot occurs in nearly 1 in every 1,000 live births worldwide, representing a significant burden of disease. In high-income countries, an evidence-based treatment protocol utilizing sequential casting was pioneered by Ponseti and has resulted in excellent outcomes among children treated for this condition. However, treatment methods and results of treatment vary greatly across low- and middle-income countries (LMICs). Our goal was to create a framework for understanding how effective programs that treat clubfoot in LMICs choose and organize their activities. METHODS: A systematic literature review was conducted using the keywords "developing countries" and "clubfoot." A public health analysis model known as the Care Delivery Value Chain (CDVC) was applied to discover public health practices that would optimize value over the entire course of a patient's life. RESULTS: The literature review yielded 32 unique results, seven of which met our inclusion and exclusion criteria. Review of the bibliographies yielded two additional papers for a total of nine papers. We identified seven vital steps in the clubfoot cycle of care and constructed a CDVC. CONCLUSIONS: The analysis of this CDVC model suggests six best practices that are essential to successfully scaling up clubfoot treatment programs and ensuring excellent clinical outcomes: (1) diagnosing clubfoot early; (2) organizing high-volume Ponseti casting centers; (3) using nonphysician health workers; (4) engaging families in care; (5) addressing barriers to access; (6) providing follow-up in the patient's community. These practices must be adapted to each context. Applying them will optimize outcomes when designing public health programs that deliver clubfoot care in LMICs. PMID- 24213948 TI - Determining conservation priorities. PMID- 24213949 TI - Arsenic in garden soils and vegetable crops. PMID- 24213950 TI - The geochemistry of iodine - a review. AB - Iodine has long been recognised as an important element environmentally. Despite this there are many gaps in our knowledge of its geochemistry and even where information is available much of this is based on old data which, in the light of recent data, are suspect.Iodine forms few independent minerals and is unlikely to enter most rock-forming minerals. In igneous rocks its concentration is fairly uniform and averages 0.24 mg/kg. Sedimentary rocks tend to have higher concentrations with average iodine contents of:-recent sediments 5-200 mg/kg, carbonates 2.7 mg/kg, shales 2.3 mg/kg and sandstones 0.8 mg/kg. Organic-rich sediments are particularly enriched in iodine.Soils, generally, are much richer in iodine than the parent rocks with the actual level being decided mainly by soil type and locality. Little soil iodine is water-soluble and much iodine is thought to be associated with organic matter, clays and aluminium and iron oxides. Most iodine in soils is derived from the atmosphere where, in turn, it has been derived from the oceans. Seawater has a mean iodine content of 58 MUg/L, while non-saline surface waters have lower and very variable levels. Subsurface brines and mineral waters are generally strongly enriched in iodine.Marine plants are frequently enriched in iodine while terrestrial plants have generally low contents. Iodine is essential for all mammals.Consideration of the geochemical cycle of iodine reveals that its transfer from the oceans to the atmosphere is probably the most important process in its geochemistry. PMID- 24213951 TI - Catechin-7-O-xyloside induces apoptosis via endoplasmic reticulum stress and mitochondrial dysfunction in human non-small cell lung carcinoma H1299 cells. AB - The medicinal plant Ulmus davidiana var. japonica has significant potential as a cancer chemoprevention agent. Catechin-7-O-xyloside (C7Ox) was purified from ultrafine U. davidiana var. japonica ethanol extract. In the present study, we investigated the apoptotic effect of C7Ox in the non-small cell lung cancer (NSCLC) cell line H1299. C7Ox treatment induced cell death and decreased plasma membrane integrity, an event typical of apoptosis. C7Ox-induced apoptosis was associated with the proteolytic activation of caspase-6, cleavage of poly(ADP ribose) polymerase (PARP) and loss of mitochondrial membrane potential. C7Ox also induced the endoplasmic reticulum (ER) stress-regulated pro-apoptotic transcription factor CHOP. The suppression of CHOP expression significantly decreased C7Ox-induced cell death, LDH leakage and caspase-6 activation. Antitumor effects, evaluated based on protracted tumor regression, were observed when nude-mice bearing H1299 xenografts were treated with C7Ox. C7Ox-induced tumor regression was accompanied by enhanced expression of CHOP mRNA. Our data suggest that C7Ox can trigger mitochondrial-mediated apoptosis, and that ER stress is critical for C7Ox-induced apoptosis in H1299 NSCLC cells. PMID- 24213952 TI - Withholding parenteral nutrition during critical illness increases plasma bilirubin but lowers the incidence of biliary sludge. AB - Cholestatic liver dysfunction (CLD) and biliary sludge often occur during critical illness and are allegedly aggravated by parenteral nutrition (PN). Delaying initiation of PN beyond day 7 in the intensive care unit (ICU) (late PN) accelerated recovery as compared with early initiation of PN (early PN). However, the impact of nutritional strategy on biliary sludge and CLD has not been fully characterized. This was a preplanned subanalysis of a large randomized controlled trial of early PN versus late PN (n = 4,640). In all patients plasma bilirubin (daily) and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], twice weekly; n = 3,216) were quantified. In a random predefined subset of patients, plasma bile acids (BAs) were also quantified at baseline and on days 3, 5, and last ICU-day (n = 280). Biliary sludge was ultrasonographically evaluated on ICU-day 5 (n = 776). From day 1 after randomization until the end of the 7-day intervention window, bilirubin was higher in the late PN than in the early PN group (P < 0.001). In the late PN group, as soon as PN was started on day 8 bilirubin fell and the two groups became comparable. Maximum levels of GGT, ALP, and ALT were lower in the late PN group (P < 0.01). Glycine/taurine-conjugated primary BAs increased over time in ICU (P < 0.01), similarly for the two groups. Fewer patients in the late PN than in the early PN group developed biliary sludge on day 5 (37% versus 45%; P = 0.04). CONCLUSION: Tolerating substantial caloric deficit by withholding PN until day 8 of critical illness increased plasma bilirubin but reduced the occurrence of biliary sludge and lowered GGT, ALP, and ALT. These results suggest that hyperbilirubinemia during critical illness does not necessarily reflect cholestasis and instead may be an adaptive response that is suppressed by early PN. PMID- 24213953 TI - Tamoxifen or letrozole versus standard methods for women with estrogen-receptor positive breast cancer undergoing oocyte or embryo cryopreservation in assisted reproduction. AB - BACKGROUND: Cryopreservation of oocytes or embryos preceded by controlled ovarian stimulation (COS) can increase the chance of future pregnancy in women with breast cancer who risk therapy-induced ovarian failure. In women with estrogen receptor (ER) positive breast cancer, alternative COS protocols with tamoxifen or letrozole are being used to theoretically inhibit breast cancer growth during COS. OBJECTIVES: To assess the effects of tamoxifen or letrozole, in addition to standard COS protocols, on the breast cancer-free interval in premenopausal women with ER positive breast cancer who undergo COS for embryo or oocyte cryopreservation. SEARCH METHODS: We searched the Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, and EBSCOhost CINAHL. We applied no limitations in year of publication or language. In addition, we searched trial registers for ongoing and registered trials, conference abstracts, and sources of grey literature. The search was conducted in January 2013. SELECTION CRITERIA: Randomised trials comparing different COS protocols in women with breast cancer were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the titles, abstracts, or both sections according to Cochrane guidelines. If data to include were provided, data extraction would have been independently performed by two review authors by using forms designed according to Cochrane guidelines. MAIN RESULTS: No randomised controlled trials were found that met the inclusion criteria. AUTHORS' CONCLUSIONS: COS schedules with the additional use of tamoxifen or letrozole are commonly chosen as an alternative regimen in young women with ER positive breast cancer who undergo COS for oocyte or embryo cryopreservation. No randomised controlled trials support the idea that these alternative COS schedules are superior to standard COS. PMID- 24213954 TI - A robotic system for quantitative assessment and poststroke training of forelimb retraction in mice. AB - BACKGROUND: Neurorehabilitation protocols based on the use of robotic devices have recently shown to provide promising clinical results. However, their efficacy is still limited because of the poor comprehension of the mechanisms at the basis of functional enhancements. OBJECTIVE: To increase basic understanding of robot-mediated neurorehabilitation by performing experiments on a rodent model of stroke. METHODS: Mice were trained to pull back a handle on a robotic platform and their performances in the task were evaluated before and after a focal cortical ischemic stroke. The platform was designed for the quantitative assessment of forelimb function via a series of parameters (time needed to complete the task, t-target; average force; number of sub-movements). RESULTS: The animals rapidly learned the retraction task and reached asymptotic performance by the fifth session of training. Within 2 to 6 days after a small, endothelin-1-induced lesion in the caudal forelimb area, mice showed an increase in t-target and number of sub-movements and a corresponding decrease in the average force exerted. These parameters returned to baseline, pre-lesion values with continued platform training (10-14 days after stroke). CONCLUSIONS: These results highlight the utility of the devised platform for characterizing post infarct deficits and improvements of forelimb performance. Further research is warranted to widen the understanding of device-dependent rehabilitation effects. PMID- 24213955 TI - Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study. AB - BACKGROUND: Exercise may decrease the risk of Parkinson's disease (PD) in humans and reduce PD symptoms in animal models. The beneficial effects have been linked to increased levels of neurotrophic factors. OBJECTIVE: We examined whether intensive rehabilitation treatment reduces motor disability in patients in the early stages of PD and increases brain-derived neurotrophic factor (BDNF) serum levels. METHODS: Thirty participants in the early stages of PD treated with rasagiline were randomly assigned to 3 hours of rehabilitation treatment that included aerobic exercise for 28 days (Group 1) or to not therapy (control; Group 2). BDNF serum levels were assessed at time T0 (baseline, before treatment), T1 (10 days), T2 (20 days), and T3 (28 days). At T0 and T3, we assessed the Unified Parkinson's Disease Rating Scale (UPDRS) III in both groups, as well as the UPDRS II and total, Berg Balance Scale, and 6-minute walking test only in Group 1. RESULTS: BDNF levels significantly increased at T1 in Group 1, an increase that was maintained throughout the treatment period. At T3 compared to T0, UPDRS III scores significantly improved in Group 1 along with scores for UPDRS II, total, Berg Balance Scale, and 6-minute walking test. CONCLUSIONS: Intensive rehabilitation treatment increases the BDNF levels and improves PD signs in patients in the early stages of the disease. These results are in line with studies on animal models of PD and healthy subjects. PMID- 24213956 TI - Combining afferent stimulation and mirror therapy for rehabilitating motor function, motor control, ambulation, and daily functions after stroke. AB - BACKGROUND: Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. OBJECTIVE: To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. METHODS: Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton 3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. RESULTS: FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. CONCLUSIONS: MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated. PMID- 24213957 TI - Spectral analyses of wrist motion in individuals poststroke: the development of a performance measure with promise for unsupervised settings. AB - BACKGROUND: Upper extremity use in daily life is a critical ingredient of continued functional recovery after cerebral stroke. However, time-evolutions of use-dependent motion quality are poorly understood due to limitations of existing measurement tools. OBJECTIVE: Proof-of-concept study to determine if spectral analyses explain the variability of known temporal kinematic movement quality (ie, movement duration, number of peaks, jerk) for uncontrolled reach-to-grasp tasks. METHODS: Ten individuals with chronic stroke performed unimanual goal directed movements using both hands, with and without task object present, wearing accelerometers on each wrist. Temporal and spectral measures were extracted for each gesture. The effects of performance condition on outcome measures were determined using 2-way, within subject, hand (nonparetic vs paretic) * object (present vs absent) analysis of variance. Regression analyses determined if spectral measures explained the variability of the temporal measures. RESULTS: There were main effects of hand on all 3 temporal measures and main effects of object on movement duration and peaks. For the paretic limb, spectral measures explain 41.2% and 51.1% of the variability in movement duration and peaks, respectively. For the nonparetic limb, spectral measures explain 40.1%, 42.5%, and 27.8% of the variability of movement duration, peaks, and jerk, respectively. CONCLUSIONS: Spectral measures explain the variability of motion efficiency and control in individuals with stroke. Signal power from 1.0 to 2.0 Hz is sensitive to changes in hand and object. Analyzing the evolution of this measure in ambient environments may provide as yet uncharted information useful for evaluating long-term recovery. PMID- 24213958 TI - Transcranial direct current stimulation to lessen neuropathic pain after spinal cord injury: a mechanistic PET study. AB - BACKGROUND: It is suggested that transcranial direct current stimulation (tDCS) can produce lasting changes in corticospinal excitability and can potentially be used for the treatment of neuropathic pain. However, the detailed mechanisms underlying the effects of tDCS are unknown. OBJECTIVE: We investigated the underlying neural mechanisms of tDCS for chronic pain relief using [(18)F] fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET). METHODS: Sixteen patients with neuropathic pain (mean age 44.1 +/- 8.6 years, 4 females) due to traumatic spinal cord injury received sham or active anodal stimulation of the motor cortex using tDCS for 10 days (20 minutes, 2 mA, twice a day). The effect of tDCS on regional cerebral glucose metabolism was evaluated by [(18)F]FDG-PET before and after tDCS sessions. RESULTS: There was a significant decrease in the numeric rating scale scores for pain, from 7.6 +/- 0.5 at baseline to 5.9 +/- 1.8 after active tDCS (P = .016). We found increased metabolism in the medulla and decreased metabolism in the left dorsolateral prefrontal cortex after active tDCS treatment compared with the changes induced by sham tDCS. Additionally, an increase in metabolism after active tDCS was observed in the subgenual anterior cingulate cortex and insula. CONCLUSION: The results of this study suggest that anodal stimulation of the motor cortex using tDCS can modulate emotional and cognitive components of pain and normalize excessive attention to pain and pain-related information. PMID- 24213959 TI - Preserved foot motor cortex in patients with complete spinal cord injury: a functional near-infrared spectroscopic study. AB - BACKGROUND: Since the brain is intact, persons with a spinal cord injury (SCI) might benefit from a brain-computer interface (BCI) to improve mobility by making use of functional near-infrared spectroscopy (fNIRS). OBJECTIVE: We aimed to use fNIRS to detect contralateral primary motor cortex activity during attempted foot movements in participants with complete SCI. METHODS: A 6-channel fNIRS, including 2 reference channels, measured relative concentration changes of oxy- (HbO) and deoxy-hemoglobin (HbR) in the contralateral motor cortex for the right foot. Seven subjects, studied within 18 months after injury, performed 12 trials of attempted right foot and real hand movements. RESULTS: T tests revealed significant HbO and HbR responses of the left motor cortex for attempted foot movements, but not for right hand movements. A 2-way repeated-measures analysis of variance revealed a larger decrease in HbR for attempted foot movements compared to hand movements. Individual results show major interindividual differences in (number of) channels activated and the sensitive chromophore (HbR or HbO). CONCLUSIONS: On group level, activity in the motor cortex of the foot can be measured with fNIRS in patients with complete SCI during attempted foot movements and might in principle be used in future BCI studies and applications. PMID- 24213960 TI - Repetitive mass practice or focused precise practice for retraining walking after incomplete spinal cord injury? A pilot randomized clinical trial. AB - BACKGROUND: Retraining walking following spinal cord injury using visually guided tasks may be especially efficacious because it engages the motor cortex, whose input may facilitate improvements in functional walking. OBJECTIVES: To contrast 2 methods of retraining, one emphasizing precise, visually guided walking over obstacles and on targets (Precision Training), the other emphasizing mass practice of walking on a treadmill (Endurance Training). METHODS: A randomized, single-blind, crossover design was used. Twenty-two participants, >=7 months postinjury, were randomly allocated to start with Precision or Endurance Training. Each phase of training was 5 times per week for 2 months, followed by a 2-month rest. MEASURES: of walking speed, distance, skill, confidence, and depression were obtained before training, then monthly thereafter. RESULTS: Both forms of training led to significant improvements in walking, with Endurance Training inducing bigger improvements in walking distance than Precision Training, especially for high-functioning walkers who had initial walking speeds >0.5 m/s. The largest improvements in walking speed and distance occurred in the first month of Endurance Training, with minimal changes in the second month of training. In contrast, improvements in walking skill occurred over both months during both types of training. Retention of over ground walking speed, distance, and skill was excellent for both types of training. CONCLUSIONS: Intensive walking training in the chronic phase after spinal cord injury is effective in improving over ground walking. Visually guided tasks for training individuals with chronic spinal cord injury were not superior to mass practice on a treadmill. PMID- 24213961 TI - Randomized Trial of Transcranial Direct Current Stimulation and Hearing Aids for Tinnitus Management. AB - Background The perception of sound in the absence of an external sound is tinnitus. Tinnitus can have a severe negative impact on quality of life. Objective This trial investigated whether multisession anodal transcranial direct current stimulation (tDCS) of the left temporoparietal area would enhance sound therapy from hearing aids. Methods Forty participants (mean age = 54 years) experiencing chronic tinnitus (minimum 2 years) completed a 7-month long double blind randomized clinical trial. Participants were randomized into 2 groups: control receiving sham tDCS and experimental receiving tDCS. Each group underwent multisession (5 consecutive sessions with 24-hour gap) anodal tDCS (2 mA intensity and 20 minutes duration) of the left temporoparietal area, followed by hearing aid use for 6 months. The impact of tDCS and hearing aid use on tinnitus was assessed using questionnaires (primary measure: Tinnitus Functional Index) and minimum masking level measurement. Results There was a significant reduction in the overall Tinnitus Functional Index score with time, F(2, 37) = 11.9, P = .0001, for both the groups. Similar patterns were seen for secondary measures. tDCS appeared to have a positive effect on minimum masking levels but not questionnaire responses. Conclusions After 3 months of hearing aid use, there were significant improvements in tinnitus, which were sustained at 6 months of use. The hearing aid effects appeared independent of tDCS. Further investigations of tDCS or other neuromodulators priming the auditory system for sound therapy based tinnitus treatments are warranted. PMID- 24213962 TI - Randomized controlled trial of light therapy for fatigue following traumatic brain injury. AB - BACKGROUND: Fatigue is a common, persistent complaint following traumatic brain injury (TBI). Effective treatment is not well established. OBJECTIVE: .The current study aimed to investigate the efficacy of 4 weeks of light therapy for fatigue in patients with TBI. METHODS: We undertook a randomized, placebo controlled study of 4-week, 45 min/morning, home-based treatment with short wavelength (blue) light therapy (lambdamax = 465 nm, 84.8 uW/cm(2), 39.5 lux, 1.74 * 10(14) photons/cm(2)/s) compared with yellow light therapy (lambdamax = 574 nm, 18.5 uW/cm(2), 68 lux, 1.21 * 10(12) photons/cm(2)/s) containing less photons in the short wavelength range and a no treatment control group (n = 10 per group) in patients with TBI who self-reported fatigue and/or sleep disturbance. Assessments of fatigue and secondary outcomes (self-reported daytime sleepiness, depression, sleep quality, and sustained attention) were conducted over 10 weeks at baseline (week -2), midway through and at the end of light therapy (weeks 2 and 4), and 4 weeks following cessation of light therapy (week 8). RESULTS: After controlling age, gender, and baseline depression, treatment with high-intensity blue light therapy resulted in reduced fatigue and daytime sleepiness during the treatment phase, with evidence of a trend toward baseline levels 4 weeks after treatment cessation. These changes were not observed with lower-intensity yellow light therapy or no treatment control conditions. There was also no significant treatment effect observed for self-reported depression or psychomotor vigilance performance. CONCLUSIONS: Blue light therapy appears to be effective in alleviating fatigue and daytime sleepiness following TBI and may offer a noninvasive, safe, and nonpharmacological alternative to current treatments. PMID- 24213963 TI - Nonlinguistic cognitive impairment in poststroke aphasia: a prospective study. AB - BACKGROUND AND OBJECTIVES: Information on cognitive impairment in aphasic patients is limited. Our aim was to investigate the prevalence and course of nonlinguistic cognitive impairments in the first year after stroke and their association with aphasia and functional outcome. METHODS: We included 147 patients with acute aphasia. At 3 months and 1 year, we assessed cognition with a nonlinguistic cognitive examination including abstract reasoning, visual memory, visual perception and construction, and executive functioning. We assessed language with a verbal communication rating (Aphasia Severity Rating Scale), the ScreeLing (a linguistic-level screening test), and the Token Test. We evaluated functional outcome with the modified Rankin scale and registered the use of antidepressants. RESULTS: In total, 107 (88%) patients had impairments in at least one nonlinguistic cognitive domain at 3 months and 91 (80%) at 1 year. The most frequently observed impairment concerned visual memory (83% at 3 months; 78% at 1 year) and the least frequent visual perception and construction (19% at 3 months; 14% at 1 year). There was improvement on all cognitive domains including language, except for abstract reasoning. Patients with persisting aphasia had lower cognitive domain scores, worse functional outcome, and were more often depressed than patients who had recovered from aphasia. CONCLUSIONS: Standard nonlinguistic cognitive examination is recommended in aphasic stroke patients. Nonlinguistic cognitive impairments are common and associated with poor functional outcome and depression, especially in patients with persisting aphasia. PMID- 24213964 TI - Comparative direct infusion ion mobility mass spectrometry profiling of Thermus thermophilus wild-type and mutant ?cruC carotenoid extracts. AB - The major carotenoid species isolated from the thermophilic bacterium Thermus thermophilus HB27 have been identified as zeaxanthin-glucoside-fatty acid esters (thermozeaxanthins and thermobiszeaxanthins). Most of the genes of the proposed T. thermophilus carotenoid pathway could be found in the genome, but there is less clarity about the genes which encode the enzymes performing the final carotenoid glycosylation and acylation steps. To get a further insight into the biosynthesis of thermo(bis)zeaxanthins in T. thermophilus, we deleted the megaplasmid open reading frame TT_P0062 (termed cruC) by both exchanging it with a kanamycin resistance cassette (DeltacruC:kat) and by generating a markerless gene deletion strain (DeltacruC). A fast and efficient electrospray ionization ion mobility-time-of-flight mass spectrometry method via direct infusion was developed to compare the carotenoid profiles of wild type and mutant T. thermophilus cell culture extracts. These comparisons revealed significant alterations in the carotenoid composition of the DeltacruC mutant, which was found to accumulate zeaxanthin. This is the first experimental evidence that the ORF encodes the glycosyltransferase enzyme necessary for the glycosylation of zeaxanthin in the final modification steps of the thermozeaxanthin biosynthesis in T. thermophilus HB27. Also, the proposed method for direct determination of carotenoid amounts and species in crude acetone extracts represents an improvement over existing methods in terms of speed and sensitivity and may be applicable in high-throughput analyses of other terpenoids as well as other important bacterial metabolites like fatty acids and their derivatives. PMID- 24213965 TI - Environmental contaminants in nonviable eggs of the endangered Mississippi sandhill crane (Grus canadensis pulla). AB - Our objectives were to determine if concentrations of environmental pollutants and microbial contamination in nonviable eggs of the endangered Mississippi sandhill crane (Grus canadensis pulla) contributed to egg failure. Six eggs collected in 1990 and four in 1991 contained only background levels of organochlorine pesticides and polychlorinated biphenyls (PCBs), and tests for microbial contamination were all negative. Two eggs contained late dead embryos, but neither revealed obvious abnormalities. Three eggs contained potentially harmful concentrations (23, 39, 146 pg/g, wet mass) of polychlorinated dibenzo-p dioxins (PCDDs) and dibenzofurans (PCDFs), based on 2,3,7,8-tetrachlorodibenzo-p dioxin equivalents (TCDD-EQ) for combined compounds. Because of the scarcity of material suitable for laboratory examination and the endangered status of the crane, we recommend that nonviable eggs continue to be monitored for toxic pollutants. PMID- 24213966 TI - The efficacy of a limestone doser to mitigate stream acidification in a Maryland coastal plain stream: Implications for migratory fish species. AB - The objective of this two-year study was to determine the efficacy of an automated limestone slurry doser to neutralize acidic pulses and improve water quality conditions for enhancing survival of early life stages of migratory fish species in a Maryland coastal plain stream. Implications for survival of early life stages of migratory fish species such as yellow perch (Perca flavescens), white perch (Morone americana), blueback herring (Alosa aestivalis) and alewife (Alosa pseudoharengus) are discussed based on the improved chemical conditions in the dosed area of the stream. Despite problems with overdosing in 1991 and failure of the stage transducer to work properly in 1992, the doser was generally effective in neutralizing acidic pulses (pH depressions) in the stream during three major rain events in both years. Chemical conditions (pH and inorganic monomeric aluminum) reported in the non-dosed area during major rainfall events were potentially stressful to both alewife and blueback herring although neither species was reported spawning in the stream during either year. Mitigating the potential impact of acidic conditions on early life stages of important migratory fish species was not sufficient to ensure spawning. It is therefore recommended that habitat improvement measures and well designed fish stocking programs be implemented concurrently with doser operations if the goal is to create optimum spawning conditions for migratory species. PMID- 24213967 TI - Principal component analysis of data for trace elements and main components in precipitation falling on Norway. AB - Trace elements and the main components in precipitation were measured at three background sites in Norway. The work is based on weekly samples from 1989 and 1990. Principal component analysis was used to detect the covariation of the chemical components in the data set. Dominant factors are long-range atmospheric transport of anthropogenic components to Norway, crustal material, and marine sources. Different local sources also exist. The interpretation of seasonal variations in the data set is eased by studying the changes in the factor scores throughout the year. Distinct seasonal patterns are shown for some of the factors, in particular those representing soil dust and atmospheric transport from the marine environment. PMID- 24213968 TI - Diatoms as indicators in the Environmental Monitoring and Assessment Program Surface Waters (EMAP-SW). AB - As a part of the U.S. Environmental Protection Agency's Environmental Monitoring and Assessment Program-Surface Waters (EMAP-SW), sedimentary diatom assemblages were studied from 66 lakes in the northeastern U.S.A. to evaluate the applicability of diatoms for this nation-wide monitoring program. Sediment cores were collected from the study lakes and diatoms were analyzed from the top (present-day) and bottom (pre-industrial) sediment samples. Canonical correspondence analysis (CCA) was used to examine which environmental variables correlate most closely with the distributions of diatom taxa in the top (surface) samples. Forward selection and Monte Carlo permutation tests showed that diatom species distributions were significantly related to total lakewater phosphorus (TP), pH, chloride, Secchi depth, and lake size and maximum depth. We developed weighted-averaging calibration and regression models for inferring TP (r (2)=0.62), chloride (r (2)=0.61), pH (r (2)=0.86), and Secchi depth (r (2)=0.62). An index of overall lake disturbance was also developed. Our diatom data indicate that marked changes have occurred in the study lakes since pre-industrial times as a result of anthropogenic activity. PMID- 24213969 TI - Nodal recurrence in the lateral neck after total thyroidectomy with prophylactic central neck dissection for papillary thyroid cancer. AB - PURPOSE: The aim of this study was to examine risk factors for nodal recurrence in the lateral neck (NRLN) in patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy with prophylactic central neck dissection (TT + pCND). METHODS: This was a retrospective cohort study of patients with PTC who underwent TT + pCND. Data of all patients treated over a 10-year period (between 1998 and 2007) were analysed. The primary outcome was prevalence of NRLN within the 5-year follow-up after initial surgery. Predictors of NRLN were determined in the univariable and multivariable analysis. RESULTS: Of 760 patients with PTC included in this study, 44 (6.0 %) developed NRLN. In the univariable analysis, the following factors were identified to be associated with an increased risk of NRLN: positive/negative lymph node ratio >=0.3 (odds ratio (OR) 14.50, 95 % confidence interval (CI) 7.21 to 29.13; p < 0.001), central lymph node metastases (OR 7.47, 95 % CI 3.63 to 15.38; p < 0.001), number of level VI lymph nodes <6 in the specimen (OR 2.88, 95 % CI 1.21 to 6.83; p = 0.016), extension through the thyroid capsule (OR 2.55, 95 % CI 1.21 to 5.37; p = 0.013), localization of the tumour within the upper third of the thyroid lobe (OR 2.35, 95 % CI 1.27 to 4.34; p = 0.006) and multifocal lesions (OR 1.85, 95 % CI 1.01 to 3.41; p = 0.048). CONCLUSIONS: Central lymph node metastases together with positive to negative lymph node ratio >=0.3 represent the strongest independent prognostic factors for the PTC recurrence in the lateral neck. PMID- 24213970 TI - Science, sentiment, and the state: community genetics and pursuit of public health in Cuba. AB - Contributing to an emerging field of social science literature by examining the translation of genomic medicine across global and transnational fields of research and medicine, this article examines how genetics is allied to public health in Cuba. It examines the sociopolitical and cultural discourses and practices that constitute community genetics or challenge or impede the translation and expansion of genomics as public health. Focusing on the experience of health practitioners, the article explores how their work is circumscribed by cultural values and social ideologies that collectively reveal an unexpected heterogeneity in how genetics is being constituted and reproduced. Although the Western quest for genomics as "personal medicine" is revealed here as both ideologically and practically problematic, such challenges paradoxically work to reinforce a commitment to maintaining the distinctive field of Cuban community genetics in its orientation to collective public health. PMID- 24213971 TI - Co-expression of gamma2 subunits hinders processing of N-linked glycans attached to the N104 glycosylation sites of GABAA receptor beta2 subunits. AB - GABAA receptors, the major mediators of fast inhibitory neuronal transmission, are heteropentameric glycoproteins assembled from a panel of subunits, usually including alpha and beta subunits with or without a gamma2 subunit. The alpha1beta2gamma2 receptor is the most abundant GABAA receptor in brain. Co expression of gamma2 with alpha1 and beta2 subunits causes conformational changes, increases GABAA receptor channel conductance, and prolongs channel open times. We reported previously that glycosylation of the three beta2 subunit glycosylation sites, N32, N104 and N173, was important for alpha1beta2 receptor channel gating. Here, we examined the hypothesis that steric effects or conformational changes caused by gamma2 subunit co-expression alter the glycosylation of partnering beta2 subunits. We found that co-expression of gamma2 subunits hindered processing of beta2 subunit N104 N-glycans in HEK293T cells. This gamma2 subunit-dependent effect was strong enough that a decrease of gamma2 subunit expression in heterozygous GABRG2 knockout (gamma2(+/-)) mice led to appreciable changes in the endoglycosidase H digestion pattern of neuronal beta2 subunits. Interestingly, as measured by flow cytometry, gamma2 subunit surface levels were decreased by mutating each of the beta2 subunit glycosylation sites. The beta2 subunit mutation N104Q also decreased GABA potency to evoke macroscopic currents and reduced conductance, mean open time and open probability of single channel currents. Collectively, our data suggested that gamma2 subunits interacted with beta2 subunit N-glycans and/or subdomains containing the glycosylation sites, and that gamma2 subunit co-expression-dependent alterations in the processing of the beta2 subunit N104 N-glycans were involved in altering the function of surface GABAA receptors. PMID- 24213972 TI - Effects of amide creatine derivatives in brain hippocampal slices, and their possible usefulness for curing creatine transporter deficiency. AB - The creatine/phosphocreatine system carries ATP from production to consumption sites and buffers the intracellular content of ATP at times of energy deprivation. The creatine transporter deficiency syndrome is an X-linked disease caused by a defective creatine transporter into the central nervous system. This disease is presently untreatable because creatine lacking its carrier cannot cross neither the blood-brain barrier nor the cell plasma membranes. Possible strategies to cure this condition are to couple creatine to molecules which have their own carrier, to exploit the latter to cross biological membranes or to modify the creatine molecule to make it more lipophilic, in such a way that it may more easily cross lipid-rich biological membranes. Such molecules could moreover be useful for treatment of stroke or other ischemic brain syndromes of normal (transporter working) tissue. In this paper we tested four molecules in in vitro hippocampal slices experiments to investigate whether or not they had a neuroprotective effect similar to that of creatine. On two of them we also performed biochemical measurements to investigate whether or not they were able to increase the creatine and phosphocreatine content of the hippocampal slices with and without block of the transporter. We found that these molecules increase levels of creatine after block of the transporter, and significantly increased the levels of phosphocreatine. Both significantly increased the total creatine content in both conditions of active and blocked transporter. This shows that these molecules are capable of entering cells through biological membranes without using the creatine transporter. By contrast, neither of them was able to delay synaptic block during anoxia of normal (transporter functioning) tissue. We conclude that these compounds might possibly be useful for therapy of creatine transporter deficiency, but further research is needed to understand their possible role in anoxia/ischemia of normal tissue. PMID- 24213973 TI - The neurocognitive effects of simulated use-of-force scenarios. AB - While the physiologic effects of modern conducted electrical weapons (CEW) have been the subject of numerous studies, their effects on neurocognitive functioning, both short-term and long-term, are less well understood. It is also unclear how these effects compare to other use-of-force options or other arrest related stressors. We compared the neurocognitive effects of an exposure to a TASER((r)) (TASER International, Inc, Scottsdale, AZ) X26TM CEW to four other use of-force scenarios during a training exercise using a well-established neurocognitive metric administered repeatedly over 1 h. Overall, we found that there was a decline in neurocognitive performance immediately post-scenario in all groups, but this effect was transient, of questionable clinical significance, and returned to baseline by 1 h post-scenario. PMID- 24213974 TI - Increased systemic cardiac output improves arterial oxygen saturation in bidirectional cavopulmonary shunt. AB - The low arterial oxygen saturation (SaO2) after bidirectional cavopulmonary shunt (BCPS) predicts poor prognosis. The venous oxygen saturation of inferior vena cava (SivcO2), as well as the pulmonary blood flow/systemic blood flow ratio (Q p/Q s) affects the SaO2. The purpose of this study is to determine whether SivcO2 or Q p/Q s should be increased to achieve better outcomes after BCPS. Forty-eight patients undergoing BCPS were included. Data of patients' age and body weight, SivcO2, Q p/Q s, pulmonary artery (PA) pressure and resistance, PA area index, morphology of ventricle, atrioventricular valve regurgitation, and history of PA plasty were collected. Stepwise multiple logistic regression analyses were used to investigate which of the factors most affected the SaO2 after BCPS. There was a significant correlation between SivcO2 and SaO2 (r = 0.771, P < 0.00001). There was no strong correlation between Q p/Q s and SaO2 (r = 0.358, P < 0.05). Stepwise multiple logistic regression analyses revealed that both SivcO2 (r = 0.49, 95 % confidence interval (CI) 0.37-0.62, P < 0.0001) and Q p/Q s (r = 11.1, 95 % CI 3.3-18.9, P = 0.007) most affected SaO2 after BCPS. Since the SivcO2 has a stronger correlation than Q p/Q s with SaO2, despite the fact that both raising Q p/Q s and raising cardiac output can increase SaO2, raising cardiac output should be considered prior to Q p/Q s to raise the SaO2 after BCPS. PMID- 24213975 TI - Language production: Methods and methodologies. AB - Methodological problems have been a longstanding barrier to the systematic exploration of issues in language production. Recently, however, production research has broadened beyond traditional observational approaches to include a diverse set of experimental paradigms. This review surveys the observational and experimental methods that are used to study production, the questions to which the methods have been directed, and the theoretical assumptions that the methods embody. Although tailored to the investigation of language production, most of the methods are closely related to others that are widely employed in cognitive research. The common denominator of these procedures is verbal responding. Because the processing complexities of verbal responses are sometimes overlooked in research on memory, perception, attention, and language comprehension, the methodological assumptions of production research have implications for other experimental procedures that are used to elicit spoken words or sentences. PMID- 24213976 TI - Working memory and language comprehension: A meta-analysis. AB - This paper presents a meta-analysis of the data from 6,179 participants in 77 studies that investigated the association between working-memory capacity and language comprehension ability. A primary goal of the meta-analysis was to compare the predictive power of the measures of working memory developed by Daneman and Carpenter (1980) with the predictive power of other measures of working memory. The results of the meta-analysis support Daneman and Carpenter's (1980) claim that measures that tap the combined processing and storage capacity of working memory (e.g., reading span, listening span) are better predictors of comprehension than are measures that tap only the storage capacity (e.g., word span, digit span). The meta-analysis also showed that math process plus storage measures of working memory are good predictors of comprehension. Thus, the superior predictive power of the process plus storage measures is not limited to measures that involve the manipulation of words and sentences. PMID- 24213977 TI - On testing for stochastic dissociations. AB - Methods for examining stochastic relationships have been proposed as powerful ways to dissociate different underlying psychological processes, but a number of problems have undermined conclusions based upon these methods. These testing methods and criticisms are reviewed, and the statistical methods for the testing of stochastic dependence are examined using computer simulation. With each of the methods examined, there were difficulties dealing with certain situations that are likely to occur in experiments examining dependence between successive tests. Examination also showed that the sample sizes of some previous studies were insufficient for findings of moderate amounts of dependence, calling some conclusions of stochastic independence into question. The results of the studies presented here suggest that testing for statistical dependence is a statistically perilous technique, but they also suggest several ways in which dedicated users of this form of testing can strengthen its application. PMID- 24213978 TI - Chimpanzee handedness revisited: 55 years since Finch (1941). AB - Chimpanzees and other great apes have long held the fascination of psychologists because of their morphological and behavioral similarities to humans. This paper describes the historical interest in studies on chimpanzee handedness and reviews current findings. Data are presented which suggest that transient changes in posture result in the transient expression of right-handedness in chimpanzees. The role of tool use as an evolutionary mechanism underlying the expression of right-handedness is challenged. Rather, emphasis is placed on the role of bimanual feeding as a behavioral adaptation for the expression of handedness. Suggestions for further research on the nature of nonhuman primate handedness are made in light of these findings. PMID- 24213979 TI - Molar and latent models of cognitive slowing: Implications for aging, dementia, depression, development, and intelligence. AB - The time that it takes a group of participants to respond in simple cognitive tasks varies systematically with the identity of the group. For example, on most tasks, older adults take longer to respond than younger adults. Similarly, on most tasks, younger children take longer to respond than mature children. More generally, response time has been found to vary reliably with a number of other factors that differentiate groups of participants, including the levels of dementia, depression, and intelligence. For each factor, investigators have sought to determine whether the various mental processes are slowed identically as the level of impairment increases. They have based this determination largely on the relation between the overall response times of the relevant groups. Here it is shown how one can base this determination on the relation between the speeds of the individual latent or mental processes governing the performance of the target groups. Such a shift in emphasis has three important advantages: it reduces the possibility of falsely accepting or rejecting the hypothesis that all processes are slowed identically; it pinpoints the actual processes that are lengthened disproportionately when processes are not slowed identically; and it makes possible the rigorous testing of the effects of changes in speed on other dependent variables (e.g., accuracy). PMID- 24213980 TI - Response conformity in recognition testing. AB - In a recognition memory test for a just-studied word list, subjects responded positively or negatively to each test word in the presence of another subject, with the two taking turns to call out their responses. Responses given second tended to conform to those given first. This was so for responses to both targets and lures and following both positive and negative first responses, although the effect was sharply reduced for targets given a negative first response. The same pattern of results was obtained in a second experiment, in which an incognito confederate replaced one of the subjects and so brought one set of responses under full experimenter control. These experiments illustrate a powerful effect of social pressure on recognition responses. PMID- 24213981 TI - A comparison of recollective memory and source monitoring. AB - Participants in recognition memory experiments are often asked for additional information about their memories after each positive recognition response. Two experiments were conducted that were identical, except that the first asked participants to make remember/familiar judgments about the items they recognized, and the second asked them to make source judgments. The similarity between the recollection and source judgment data has implications for measurement issues and theory development. PMID- 24213982 TI - Influence of emotional state on irrelevant thoughts. AB - The fan effect paradigm was used to investigate the influence of emotional mood state on longterm memory retrieval (Anderson, 1983). Subjects learned target facts embedded in unrelated sentences to a specified criterion and were then given a happy, sad, or neutral mood induction. Mean response times (RTs) and error rates were analyzed in a speeded recognition test in which subjects distinguished between the learned facts and foil facts (foil facts were constructed by recombining the same concepts). A follow-up lexical decision task indicated that mean RT was positively correlated with an increase in the weighted proportion of irrelevant thoughts produced by subjects in an induced sad mood. Results suggest that irrelevant thoughts associated with the sad mood state interfered with more relevant, task-oriented, thoughts and support the notion that sad mood is related to a failure to inhibit irrelevant information. PMID- 24213983 TI - Auditory priming in an implicit memory task that emphasizes surface processing. AB - Auditory priming was examined in an implicit memory task, phoneme monitoring, that emphasized surface processing. The contribution of voice to priming was investigated in single- and multiplespeaker environments by repeating studied words at test in either the same voice or different voices. Multiple-speaker environments, which preserved both acoustic and word repetition, eliminated priming when more than two voice changes between words were introduced. When voice familiarity attenuated acoustic variability, priming was reestablished in the condition in which three voices were heard. Voice changes between study and test, which eliminated acoustic repetition, also abolished priming. Word frequency affected reaction times but not priming. This demonstrated that priming entailed subword processing rather than word processing. This study demonstrates that the significance of voice in implicit memory is dependent on the level of processing required by the task and the acoustic environment. Supported in part by an OMRDD Fellowship in the CSI/IBR Center for Developmental Disabilities to M. P., portions of this study were conducted in partial fulfillment of her requirements for the Ph.D. in the Department of Psychology of The City University of New York Graduate School and University Center. PMID- 24213984 TI - The moderating influence of variability on belief revision. AB - The variability of the information on which a belief was initially based should moderate the degree to which the belief is revised when new disconfirming information is received. Reasoning from everyday intuitions, psychological theories of concept representation, and a rational mathematical analysis, we inferred that as variability increased, resistance to disconfirming information would also increase. Participants' judgments of the central tendencies of distributions of numerical information confirmed this prediction. PMID- 24213985 TI - Effects of contextual constraint on eye movements in reading: A further examination. AB - The effect of contextual constraint on eye movements in reading was examined by asking subjects to read sentences that contained a target word that varied in contextual constraint; high-, medium-, or low-constraint target words were used. Subjects fixated low-constraint target words longer than they did either high- or medium-constraint target words. In addition, they skipped high-constraint words more than they did either medium- or low-constraint target words. The results further confirm that contextual constraint has a strong influence on eye movements during reading. PMID- 24213986 TI - Negative priming and stimulus-response compatibility. AB - The subjects in this study made incongruent naming responses to words and pictures that were presented on alternate trials (e.g., say "car" toBIKE). Their response time was longer if the correct response for the current trial was the name of the stimulus presented on the preceding trial, as compared with a control condition. These results suggest that the tendency to produce the (congruent) name of the stimulus is automatically activated and then inhibited. The "negative priming" effects appeared stronger for words where pictures were primes than for pictures where words were primes. The implications of these results for negative priming and stimulus-response compatibility are discussed. PMID- 24213987 TI - List context effects on masked phonological priming in the lexical decision task. AB - A lexical decision experiment tested the effects of briefly presented masked primes that were homophones or pseudohomophones of target words. Different types of nonword foil (pseudohomophones, orthographically regular nonwords, orthographically irregular nonwords) were mixed with the word targets. Pseudohomophone priming effects were independent of nonword foil variations, whereas homophone priming effects varied from being facilitatory in the presence of orthographically regular nonwords, inhibitory in the presence of pseudohomophones, and null in the presence of irregular nonwords. This dissociation in the way nonword foil variations influence masked pseudohomophone and homophone priming effects in the lexical decision task is discussed within the framework of a bimodal extension of the multiple readout model of visual word recognition (Grainger & Jacobs, 1996). PMID- 24213988 TI - Phonological priming reflects lexical competition. AB - A phonological relationship between a prime and a target produces facilitation when one or two initial phonemes are shared (low-similarity facilitation) but produces interference when more phonemes are shared (high-similarity interference; Slowiaczek & Hamburger, 1992). Although low-similarity facilitation appears to be a strategic effect (Goldinger, Luce, Pisoni, & Marcario, 1992), this result cannot generalize to high-similarity interference because the two effects are dissociated (Slowiaczek & Hamburger, 1992). In the present study, strategic processing in high-similarity interference was investigated. The phonological relatedness proportion (PRP) and the prime-target interstimulus interval (ISI) were varied in a shadowing experiment. Low-similarity facilitation was found only with a high PRP and long ISI, but high-similarity interference was found regardless of PRP and ISI. These results suggest that strategies influence low-similarity facilitation, but high-similarity interference reflects automatic processing. PMID- 24213989 TI - PNKP knockdown by RNA interference inhibits herpes simplex virus-1 replication in astrocytes. AB - Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases, including herpes simplex encephalitis and meningitis. According to recent studies, PNKP significantly affects the proliferation of HSV-1 in astrocytes. Here, we used viral proliferation curves to confirm the significant inhibitory effects of PNKP on HSV-1 proliferation. PNKP downregulation was also confirmed by analyzing the transcription of viral genes. We found that PNKP downregulation affects the viral DNA copy number. This study preliminarily confirms that PNKP affects viral proliferation by affecting HSV-1 genome cyclization. These results also suggest that astrocytes play a specific role in preventing HSV-1 infection. PMID- 24213990 TI - Resilience and challenges of marine social-ecological systems under complex and interconnected drivers. AB - In this paper, we summarize the contributions made by an interdisciplinary group of researchers from different disciplines (biology, ecology, economics, and law) that deal with key dimensions of marine social-ecological systems. Particularly, the local and global seafood provision; the feasibility and management of marine protected areas; the use of marine ecosystem services; the institutional dimension in European fisheries, and the affordable models for providing scientific advice to small-scale fisheries. This Special Issue presents key findings from selected case studies around the world available to educators, policy makers, and the technical community. Together, these papers show that a range of diverse ecological, economic, social, and institutional components often mutually interact at spatial and temporal scales, which evidence that managing marine social-ecological systems needs a continuous adaptability to navigate into new governance systems. PMID- 24213991 TI - Exploring patterns of seafood provision revealed in the global Ocean Health Index. AB - Sustainable provision of seafood from wild-capture fisheries and mariculture is a fundamental component of healthy marine ecosystems and a major component of the Ocean Health Index. Here we critically review the food provision model of the Ocean Health Index, and explore the implications of knowledge gaps, scale of analysis, choice of reference points, measures of sustainability, and quality of input data. Global patterns for fisheries are positively related to human development and latitude, whereas patterns for mariculture are most closely associated with economic importance of seafood. Sensitivity analyses show that scores are robust to several model assumptions, but highly sensitive to choice of reference points and, for fisheries, extent of time series available to estimate landings. We show how results for sustainable seafood may be interpreted and used, and we evaluate which modifications show the greatest potential for improvements. PMID- 24213992 TI - All fish for China? AB - In this paper we examine the effect of Gross Domestic Product (GDP) on the level of fish intake in China in comparison with the rest of the world. We also analyse the origin and destination of China's seafood products in order to understand the main patterns during the last decades. The results show that in the 1961-2011 period the rate of growth of the GDP in China doubled that of other developing regions, while the daily fish intake of China increased fourfold, making China the largest fish consumer in the world. Given the size and scale of China's role in production, consumption, and global transformation of seafood markets, China is shaping a new era of industrialization in the history of the fishing industry. PMID- 24213993 TI - Why are prices in wild catch and aquaculture industries so different? AB - Through a comparative analysis of prices in capture fisheries and aquaculture sectors, the objectives of this paper are a) to investigate three the trends in prices of forage catches to feed the aquaculture species, b) to analyze the amount of fish species need to feed aquaculture species in order to assess the level of efficiency in resource use, and c) to examine the degree of economic concentration either in wild-catch industry and aquaculture sectors. The results show that prices of cultivated species are higher than prices of the same species when harvested from the sea. We explain this fact by the interplay of three forces. First, the amount of wild fish to feed aquaculture species continues to improve over time. Second, the pressure of fishing activities has not been reduced since catches of most forage fishes are declining, which induce higher prices of capture species that feed aquaculture production. Third, the level of seafood market concentration is significantly higher in aquaculture than in wild catches, which generates higher prices in aquaculture. PMID- 24213994 TI - Fish traders as key actors in fisheries: gender and adaptive management. AB - This paper fills an important gap towards adaptive management of small-scale fisheries by analyzing the gender dimension of fish trade in Zanzibar, Tanzania. We hypothesize that gender-based differences are present in the fish value chain and to test the hypothesis interviews were performed to analyze: (i) markets, customers, and mobility, (ii) material and economic resources, (iii) traded fish species, (iv) contacts and organizations, and (v) perceptions and experiences. Additionally, management documents were analyzed to examine the degree to which gender is considered. Results show that women traders had less access to social and economic resources, profitable markets, and high-value fish, which resulted in lower income. These gender inequalities are linked, among others, to women's reproductive roles such as childcare and household responsibilities. Formal fisheries management was found to be gender insensitive, showing how a crucial feedback element of adaptive management is missing in Zanzibar's management system, i.e., knowledge about key actors, their needs and challenges. PMID- 24213995 TI - Transboundary socio-ecological effects of a Marine Protected Area in the Southwest Atlantic. AB - Marine Protected Areas (MPAs) have been regarded as an alternative to protect natural resources and to improve fisheries. However, MPAs may also have negative socio-economic consequences on fishing communities. We aimed to check the effectiveness of a socially conflicting MPA in Brazil by assessing target reef fish biomass in islands inside (n = 6) and outside (n = 6) the MPA, fisheries' productivity (biomass), catch per unit of effort (CPUE), and fishers' socio economic status (mainly fishers' income) in three fishing communities subjected to different degrees of influence (close, average, and long distance) of the MPA. The CPUE was higher in the fishing community that was further away from the MPA, fish biomass was higher in the islands located inside the MPA in the southern region and in the islands located outside the MPA in the northern region, while fishers were making the most money closest to the MPA, where conflicts are the highest, probably from practicing very intensive fisheries. This integrated approach showed that the studied MPA has not delivered ecological benefits, such as higher CPUE or more fish, while higher income closer to the MPA could not be clearly attributed to its effects. PMID- 24213996 TI - Financing marine protected areas through visitor fees: insights from tourists willingness to pay in Chile. AB - Tourism is a financing mechanism considered by many donor-funded marine conservation initiatives. Here we assess the potential role of visitor entry fees, in generating the necessary revenue to manage a marine protected area (MPA), established through a Global Environmental Facility Grant, in a temperate region of Chile. We assess tourists' willingness to pay (WTP) for an entry fee associated to management and protection of the MPA. Results show 97 % of respondents were willing to pay an entrance fee. WTP predictors included the type of tourist, tourists' sensitivity to crowding, education, and understanding of ecological benefits of the MPA. Nature-based tourists state median WTP values of US$ 4.38 and Sun-sea-sand tourists US$ 3.77. Overall, entry fees could account for 10-13 % of MPA running costs. In Chile, where funding for conservation runs among the weakest in the world, visitor entry fees are no panacea in the short term and other mechanisms, including direct state/government support, should be considered. PMID- 24213997 TI - Adaptive capacity of fishing communities at marine protected areas: a case study from the Colombian Pacific. AB - Departing from a theoretical methodology, we estimate empirically an index of adaptive capacity (IAC) of a fishing community to the establishment of marine protected areas (MPAs). We carried out household surveys, designed to obtain information for indicators and sub-indicators, and calculated the IAC. Moreover, we performed a sensitivity analysis to check for robustness of the results. Our findings show that, despite being located between two MPAs, the fishing community of Bazan in the Colombian Pacific is highly vulnerable and that the socioeconomic dimension of the IAC constitutes the most binding dimension for building adaptive capacity. Bazan is characterized by extreme poverty, high dependence on resources, and lack of basic public infrastructure. Notwithstanding, social capital and local awareness about ecological conditions may act as enhancers of adaptive capacity. The establishment of MPAs should consider the development of strategies to confer adaptive capacity to local communities highly dependent on resource extraction. PMID- 24213998 TI - Determining the feasibility of establishing new multiple-use marine protected areas in Chile. AB - This paper evaluates the feasibility of establishing a multiple-use marine protected area. The methodology was applied to evaluate three proposed sites in Chile with diverse conservation needs, social stress and poverty levels, and different economic activities (small-scale fishing, heavy industry, and mining activities). We use two broad categories for the evaluation: socio-economic and political-institutional. The methodology uses a combination of secondary data with personal interviews, workshops, and focus groups with stakeholders (e.g., fishermen, unions, politicians, social organizations) from different political, social, and economic backgrounds to characterize current and potential natural and social resources and to evaluate in an ordinal scale the feasibility of establishing the protected area. The methodology allows us to correctly identify the challenges faced in each site and can be used to develop appropriate strategies for balancing economic, social, and environmental objectives. This methodology can be replicated to evaluate the feasibility of other marine or terrestrial protected areas. PMID- 24213999 TI - Connecting marine ecosystem services to human well-being: insights from participatory well-being assessment in Kenya. AB - The linkage between ecosystems and human well-being is a focus of the conceptualization of "ecosystem services" as promoted by the Millennium Ecosystem Assessment. However, the actual nature of connections between ecosystems and the well-being of individuals remains complex and poorly understood. We conducted a series of qualitative focus groups with five different stakeholder groups connected to a small-scale Kenyan coastal fishery to understand (1) how well being is understood within the community, and what is important for well-being, (2) how people's well-being has been affected by changes over the recent past, and (3) people's hopes and aspirations for their future fishery. Our results show that people conceive well-being in a diversity of ways, but that these can clearly map onto the MA framework. In particular, our research unpacks the "freedoms and choices" element of the framework and argues for greater recognition of these aspects of well-being in fisheries management in Kenya through, for example, more participatory governance processes. PMID- 24214000 TI - Linking salmon aquaculture synergies and trade-offs on ecosystem services to human wellbeing constituents. AB - Salmon aquaculture has emerged as a successful economic industry generating high economic revenues to invest in the development of Chiloe region, Southern Chile. However, salmon aquaculture also consumes a substantial amount of ecosystem services, and the direct and indirect impacts on human wellbeing are still unknown and unexplored. This paper identifies the synergies and trade-offs caused by the salmon industry on a range of ecosystem services. The results show that large economic benefits due to the increase of provisioning ecosystem services are also causing a reduction on regulating and cultural services. Despite the improvement on average income and poverty levels experienced in communities closely associated with the sector, this progress is not large enough and social welfare did not improve substantially over the last decade. The rest of human wellbeing constituents in Chiloe region have not changed significantly compared to the development in the rest of the country. PMID- 24214001 TI - How resilient are Europe's inshore fishing communities to change? Differences between the north and the south. AB - One would hypothesize that the Common Fisheries Policy, as the umbrella framework for fisheries management in the EU would have the greatest impact on fishers' communities across Europe. There are, however, biological, economic, social, and political factors, which vary among fishing communities that can affect how these communities react to changes. This paper explores the links between institutional arrangements and ecological dynamics in two European inshore fisheries socio ecological systems, using a resilience framework. The Mediterranean small-scale fishers do not seem to have been particularly affected by the Common Fisheries Policy regulations but appear affected by competition with the politically strong recreational fishers and the invasion of the rabbit fish population. The inshore fishers along the East coast of Scotland believe that their interests are not as sufficiently protected as the interests of their offshore counterpart. Decisions and initiatives at global, EU, and sometimes national level, tend to take into account those fisheries sectors which have a national economic importance. A socio-ecological analysis can shift the focus from biological and economic aspects to more sustainable long-term delivery of environmental benefits linked to human wellbeing. PMID- 24214002 TI - Credible enforcement policies under illegal fishing: does individual transferable quotas induce to reduce the gap between approved and proposed allowable catches? AB - In general, approved Total Allowable Catches (TACs) are higher than proposed TACs by the scientific assessment and reported landings approved are higher than approved TAC. We build a simple enforcement agency's behavior model that generates-as a rational behavior-those two facts. The model has two ingredients. First, there exists illegal fishing generated by an imperfect enforcement technology; second, the enforcement agency cannot commit on announced penalties. We show that lack of commitment increases the potential benefits for national enforcement agency of deviating from proposal (scientific optimal) quotas. Although the enforcement agency wants to announce a low quota target to induce a low level of illegal harvest, it will find optimal to revise the quota announced in order to reduce penalties and improve fishermen welfare. Therefore, agencies find it optimal to approve higher quotas than that proposed by the scientific advice. Our main result is to show that when full compliance is not possible, and national agencies cannot commit, the introduction of Individual Transferable Quotas increases the potential benefits for agencies of deviating from the optimal proposed TAC by the scientific advised. PMID- 24214003 TI - The key role of the Barefoot Fisheries Advisors in the co-managed TURF system of Galicia (NW Spain). AB - Many authors have pointed out the need for simpler assessment and management procedures for avoiding overexploitation in small-scale fisheries. Nevertheless, models for providing scientific advice for sustainable small-scale fisheries management have not yet been published. Here we present one model; the case of the Barefoot Fisheries Advisors (BFAs) in the Galician co-managed Territorial Users Rights for Fishing. Based on informal interviews, gray literature and our personal experience by being involved in this process, we have analyzed the historical development and evolution of roles of this novel and stimulating actor in small-scale fisheries management. The Galician BFA model allows the provision of good quality and organized fisheries data to facilitate and support decision making processes. The BFAs also build robust social capital by acting as knowledge collectors and translators between fishers, managers, and scientists. The BFAs have become key actors in the small-scale fisheries management of Galicia and a case for learning lessons. PMID- 24214004 TI - Lead, cadmium, arsenic and zinc in the ecosystem surrounding a lead smelter. AB - A lead smelter has been operating at Belledune in the province of New Brunswick, in eastern Canada, since 1966. This paper presents data on the concentrations of the four primary metals emitted from the smelter - lead, cadmium, arsenic and zinc - which were measured in the terrestrial environment near the smelter and the concentrate transport route. Deposition of these metals to the snowpack and the uptake by grass forage are discussed in relation to non-regulatory guidelines, toxicity and atmospheric emissions. A 1992 snowpack transect survey extending 0.5-40 km northwest, southeast and south of the smelter revealed lead concentrations of 2-3193 ppb, cadmium <0.10-49.7 ppb, arsenic <3.0-72.0 ppb, and zinc 3-401 ppb. Deposition estimates within this zone for lead were between 0.046 and 20.1 kg/ha/yr, cadmium <0.007 and 313 g/ha/yr, arsenic <0.016 and 453 g/ha/yr and zinc 0.020 and 2.52 kg/ha/yr. Concentrations of these metals in the snowpack were highest within 3 km of the smelter and were detectable at greater distances SE of the smelter. Lead was dispersed greater distances from the smelter than cadmium or arsenic. Snowpack samples collected within 5-20 m of the railway contained 140-7270 ppb of lead, 0.4-36.9 ppb of cadmium, <3.0-72.0 ppb of arsenic and 41-13100 ppb of zinc. Grass forage sampled within 0.6-16 km of the smelter contained lead 5-152 ppm, cadmium 0.10-4.1 ppm, and zinc 22-154 ppm. Highest concentrations of lead, cadmium and zinc in grass forage were found were found within 2.2 km of the smelter. Grass forage collected within 10-70 m of the railway contained lead 13-288 ppm, cadmium 0.4-1.3 ppm and zinc 98-831 ppm. PMID- 24214005 TI - Sanitary conditions in three creeks in Dubai, Sharjah and Ajman Emirates on the Arabian gulf (UAE). AB - A one-year monitoring program was carried out to assess the degree of pollution in three creeks on the northern coast of the United Arab Emirates (UAE), through measuring for chemical nutrients such as phosphate, ammonium, nitrate, nitrite and dissolved oxygen, in addition to enumerating selected microbial communities such as the heterotrophic bacteria, salt tolerant heterotrophic bacteria, Gram negative bacteria, total coliform and faecal coliform bacteria. The results indicated that Dubai and Sharjah creeks have occasional unusually high nutrients levels with sharp fluctuations and wide spatial and temporal variations, suggesting the presence of an anthropogenic sources of pollution, creating these conditions, near the sampling sites. These sources includes several wastewater outlets and recreational facilities. Ajman creek had much less nutrients levels. The microbial counts in the three creeks had a distinct pattern where numbers peaked in mid spring (May) and autumn (October) and were relatively low during the summer and winter months. Total and faecal coliform fluctuated depending on several factors including the presence of nearby recreation and commercial areas, but were at no time consistently high. It was concluded that there is no major pollution problem in these creeks and recommendation were made to prevent it in the future. PMID- 24214006 TI - An assessment of air quality in Karachi, Pakistan. AB - An atmospheric pollution survey was carried out at 13 sites in Karachi, Pakistan, simultaneously from 0600 h to 2100 h for 15 consecutive days in May 1990 which also included meteorological measurements. The monitoring sites were included along the prevailing wind patterns in Karachi. Carbon monoxide levels in the ambient air were found to reach 9-10 ppm along the busy urban streets whereas CO2 level exceeded 370 ppm in these areas. Our survey indicates that NO2 levels were exceeding U.S. ambient air quality standards. Maxmum NO2 concentrations were observed (0.3-0.5 ppm) during the daytime from 0600 h to 2100 h. The surface ozone maximum around noon at the inland sites reached the levels of 40 ppb and 50 ppb respectively compared to upwind coastal Sites 1 level of 25 ppb. The Pb concentrations were approximately 3- to 7-fold higher than average, which corresponded well to urban air. Fossil fuel SO4 (excess) and NO3 were apportionally based on the assumption that these two anions were present as (NH4)2SO4, and NH4NO3 in the aerosols. In the eastern part of the city atmospheric sulphate (SO4) shows the combustion of coal as its source from the vicinity and downwind of a steel manufacturing plant. PMID- 24214007 TI - Locational differences in metal concentrations in feathers of Australasian gannet (Morus serrator) in New Zealand. AB - Levels of lead, cadmium, mercury, selenium, manganese and chromium were examined in breast feathers of Australasian Gannets (Morus serrator) from New Zealand waters, where they breed on coastal rocky stacks, islands, and occasionally coastal headlands. There were significant differences in the concentrations of all metals except mercury, with gannets from Ninety Mile Beach having significantly lower levels of all metals than those from the other beaches. Ninety Mile Beach is on the northern tip of the North Island, away from urbanization and industrialization, whereas the other beaches are closer to Auckland, the largest city in New Zealand. The levels of most metals were similar or lower than those reported for feathers from elsewhere around the world. Mercury, however, was at the high end, being exceeded only by raptors and gulls from industrialized countries. Several metal levels were highly correlated, indicating that gannets were usually exposed to several metals at once. PMID- 24214008 TI - The measurement of atmospheric concentrations and deposition of semi-volatile organic compounds. AB - A physical description of semi-volatile organic compounds (SVOCs) is given, both in terms of their characteristic nature in the atmosphere and the processes which control their deposition. The currently adopted methods used to measure the atmospheric concentrations of SVOCs have been summarised, along with their shortcomings. Techniques and associated problems have also been reviewed for measurements of atmospheric deposition. A summary has been given of the requirements necessary for a full assessment of atmospheric SVOCs and their deposition. PMID- 24214009 TI - Letter to the editor. PMID- 24214010 TI - Use of hold-gro erosion control fabric in the establishment of plant species on coal mine soil. AB - Experiments were conducted on the Black Mesa Coal Mine, Kayenta, Arizona in 1977 and 1978 to study the effectiveness of Hold-Gro Erosion Control Fabric (a product from the Gulf States Paper Corporation, Tuscaloosa, Alabama) in the establishment of plants on coal mine soil following the surface mining of coal. Four plant species were planted: (1) spring barley (Horduem vulgare L.), an annual grass (2) crested wheatgrass (Agropyron cristatum L.), a perennial grass (3) alfalfa (lucerne) (Medicago sativa L.), a perennial legume and (4) fourwing saltbush (Atriplex canescens Pursh.), a perennial shrub. Seeds of each plant species were planted in reclaimed coal mine soil in the spring of the year by both broadcast seeding (conventional culture) and the incorporation of seeds in Hold-Gro Erosion Control Fabric. Average numbers of seedlings established and percent ground cover for all species studied were higher in areas where conventional culture was used than they were in areas where seeds were incorporated in Hold-Gro Erosion Control Fabric. The incorporation of seeds in Hold-Gro Erosion Control Fabric in the establishment of plant species on coal mine soil was not an effective cultural practice in the southwestern United States. PMID- 24214011 TI - Survival and growth of conservation shrubs and trees, with thin-cover reclamation on acid substrate, Iowa, USA. AB - Many abandoned strip-mine sites in midwestern USA are highly acidic and require a separate layer of low-acidity cover materials for successful revegetation. Economics and logistics often constrain this reclamation to a very thin cover. Twenty-two species of shrubs and trees were tested for 6 years of survival and growth on a thin wedge of silt loess (up to 0.75m thick) emplaced over highly acid spoils, in south-central Iowa. No weed control or maintenance was provided. The performance of 21 of the species could be categorized into 3 groups: Group 1 consistent survival (10 species); Group 2-irregular survival and growth (6 species); Group 3-little suitability for survival (5 species). Mouldy nursery stock precluded evaluation of 1 species.For most species, the most favourable survival and growth was not on the thickest loess cover (0.75 meters) because weeds became too well established. In general, the shrubs survived severe weed competition in dwarfed form until they could break through the weed canopy. But the tree species had to penetrate the weed canopy within their first few years of growth or perish. There is evidence that if weed competition were reduced or eliminated, the species in Group 2 would probably have survival and growth equivalent to those in Group 1. The use of "tubelings" for establishing shrubs and trees on thincover reclamation sites is suggested. PMID- 24214012 TI - Air lead, blood lead and travel by car. AB - Evidence on the relevance of lead in petrol to lead in blood has come from two main sources. Cross sectional studies of blood lead levels in population samples and in the air to which they are exposed suggest that petrol makes only a very small contribution. However longitudinal studies in the USA in which changes in lead levels in petrol and changes in blood lead have been studied suggest that petrol makes a substantial contribution to blood lead. The possibility that this discrepancy might be explained by the exposure of subjects to very high levels of lead when travelling in motor vehicles is examined, and rejected. PMID- 24214013 TI - The effect of limestone treatments on the rate of acid generation from pyritic mine gangue. AB - Surface water enters the Haile Gold Mine, Lancaster County, South Carolina by means of a small stream and is ponded behind a dam and in an abandoned pit. This water is affected by acidic drainage. In spite of the large exposures of potentially acid producing pyritic rock, the flux of acid to the water is relatively low. Nevertheless, the resulting pH values of the mine water are low (around 3.5) due to negligible buffering capacity. In view of the observed low release of acidity, the potential for acid drainage abatement by limestone ameliorants appears feasible.This study investigated the effects of limestone treatment on acid generation rates of the Haile mine pyritic rocks through a series of leaching experiments. Below a critical alkalinity threshold value, solutions of dissolved limestone were found consistently to accelerate the rate of pyrite oxidation by varying degrees. The oxidation rates were further accelerated by admixing solid limestone with the pyritic rock. However, after a period of about a month, the pyrite oxidation rate of the admixed samples declined to a level lower than that of untreated pyrite. Leachates produced by the pyrite and limestone mixtures contained little if any iron. Further, in the mixtures, an alteration of the pyrite surface was apparent.The observed behaviour of the treated pyrite appears to be related to the immersion of the pyrite grains within a high alkalinity/high pH environment. The high pH increases the rate of oxidation of ferrous iron which results in a higher concentration of ferric iron at the pyrite surface. This, in turn, increases the rate of pyrite oxidation. Above a threshold alkalinity value, the precipitation of hydrous iron oxides at the pyrite surface eventually outpaces acid generation and coats the pyrite surface, retarding the rate of pyrite oxidation. PMID- 24214015 TI - Photoresponsive gels prepared by ring-opening metathesis polymerization. AB - This communication describes photoresponsive gels, prepared using ring-opening metathesis polymerization (ROMP), that dissolve upon irradiation with ultraviolet light. Exposure of mixtures of norbornene-type ROMP monomers and new photoreactive cross-linkers comprising two norbornene units bound through a chain containing o-nitrobenzyl esters (NBEs) to well-known ruthenium carbene catalysts gave cross-linked polymer networks that swelled in organic solvents or water depending on the structure of the monomer. These gels became homogeneous upon irradiation with UV light, consistent with breaking of the cross-links through photolysis of the NBE groups. The irradiation time required for homogenization of the gels depended on the cross-link density and the structure of the photoresponsive cross-linker. PMID- 24214017 TI - The cyanobactin heterocyclase enzyme: a processive adenylase that operates with a defined order of reaction. PMID- 24214019 TI - The gluteal sling: an anatomical study. AB - INTRODUCTION: Sciatic nerve palsy is a devastating complication which may be seen after acetabular exposure in total hip resurfacing via a posterior approach. An anatomical structure termed as the "gluteal sling" was suggested to play a role in sciatic nerve palsies during this operation. "Gluteal sling" is formed by the attachment of the deep fibers of the inferior part of the gluteus maximus on the gluteal tuberosity of the femur and the lateral intermuscular septum. It is suggested to be released to avoid such compressive injuries. The purpose of this study is to demonstrate how much of the gluteal sling should be released to decrease the tension on sciatic nerve during posterior hip arthroplasties. We also aimed to study the anatomical structures at risk during releasing procedure. MATERIALS AND METHODS: The gluteal sling was examined in 17 sides of 9 adult cadavers. Its relation with the sciatic nerve, first perforating artery, the tip of greater trochanter and the ischial tuberosity were evaluated. RESULTS: The closest distance between the gluteal sling and the sciatic nerve was measured as 1.9 +/- 0.6 cm. This point was corresponding to the distal 2/3 part of the gluteal sling. The distance of the proximal edge of the gluteal sling to the first perforating artery was 3.7 +/- 0.9 cm, while its ascending branch was closer, being 1.8 +/- 0.8 cm. CONCLUSIONS: Theoretically, it is enough to release the proximal 2/3 of the gluteal sling to avoid its compression on the sciatic nerve. However, further clinical studies would need to be undertaken to properly determine the effects of this procedure. PMID- 24214018 TI - Recent trends in biomedical informatics: a study based on JAMIA articles. AB - In a growing interdisciplinary field like biomedical informatics, information dissemination and citation trends are changing rapidly due to many factors. To understand these factors better, we analyzed the evolution of the number of articles per major biomedical informatics topic, download/online view frequencies, and citation patterns (using Web of Science) for articles published from 2009 to 2012 in JAMIA. The number of articles published in JAMIA increased significantly from 2009 to 2012, and there were some topic differences in the last 4 years. Medical Record Systems, Algorithms, and Methods are topic categories that are growing fast in several publications. We observed a significant correlation between download frequencies and the number of citations per month since publication for a given article. Earlier free availability of articles to non-subscribers was associated with a higher number of downloads and showed a trend towards a higher number of citations. This trend will need to be verified as more data accumulate in coming years. PMID- 24214020 TI - Truncus bicaroticus with aberrant right subclavian artery and origin of right vertebral from right common carotid artery. AB - We describe a rare constellation of variant anatomy of the aortic arch branches, seen on a magnetic resonance angiographic examination during the course of investigation for recent onset memory loss in a 52-year-old patient. There was a common origin of both the common carotid arteries (CCA), the common trunk being the first major branch of the aortic arch, the right vertebral artery arising from the right CCA and the right subclavian artery arising as the last branch of the arch. In isolation, the three components of this constellation have been reported with different frequencies, but as per the authors' knowledge, this entire constellation has been rarely reported. We review the literature and propose an embryological mechanism for this variant anatomy. PMID- 24214021 TI - Exploring intercellular signaling by proteomic approaches. AB - Cells live in a close social context by having mutual communication with their local microenvironment. This complex intercellular communication activates dynamic signaling pathways and regulates specific cell fate. MS-based proteomics has been approved to be inevitable for characterizing dynamic protein expression and PTMs on a global scale. However, because of technical difficulties for targeting membrane receptors and secreted proteins, especially in a physiologically relevant manner, systematic characterization of intercellular signaling by MS-based proteomics has largely lagged behind. Here, I will review the latest proteomics technology development and its application to characterizing different modes of intercellular communication including indirect and direct cell-cell communication, and protein translocalization. I will discuss how MS-based proteomics has been applied for systems-level profiling intercellular signaling in defined biological contexts including tumor microenvironment, bacteria/virus-host cell interaction, immune cell interaction, and stem cell niche. PMID- 24214022 TI - Profiling of the soluble proteome in rat hippocampus post propofol anesthesia. AB - The current study was designed to initially observe the changes in soluble proteome in rat hippocampus post anesthesia, trying to explore possible clues for elucidating the effects of propofol. Soluble proteins were separated by 2 dimensional electrophoresis (2-DE). Their expressions were observed at 1, 6, 24 h and 7 days after 3 h of propofol anesthesia. Spots exhibiting significant changes among different time-points were submitted to matrix-assisted laser desorption/ionization time of flight mass spectrometer (MALDI-TOF MS) assay and peptide mass fingerprinting identification. The expression changes of selected proteins were further assayed using Western blot and RT-PCR. Twenty-six differentially expressed proteins were found and 19 were successfully identified with MALDI-TOF MS. Gene ontology analysis revealed these identified proteins were mainly cytosol (5) and/or cytoskeleton fractions (5). According to biological processes category, 9 proteins take part in development process, 12 are involved in metabolic process and 6 in regulatory function. Functionally, 17 proteins were involved in binding activities among which 12 possessed catalytic activities. Most changes took place within 24 h. Change patterns of selected proteins were identical in 2-DE and Western blot. Three mRNA of 5 selected proteins exhibited similar change patterns with those of their protein expressions. Soluble proteome in rat hippocampus are dynamically affected by propofol, with multiple processes being involved. They are possible explanations for propofol effects but further investigations are required. PMID- 24214023 TI - Celastrol from 'Thunder God Vine' protects SH-SY5Y cells through the preservation of mitochondrial function and inhibition of p38 MAPK in a rotenone model of Parkinson's disease. AB - Celastrol, a potent natural triterpene and one of the most promising medicinal molecules, is known to possess a broad range of biological activity. Rotenone, a pesticide and complex I inhibitor, is commonly used to produce experimental models of Parkinson's disease both in vivo and in vitro. The present study was designed to examine the effects of celastrol on cell injury induced by rotenone in the human dopaminergic cells and to elucidate the possible mechanistic clues in its neuroprotective action. We demonstrate that celastrol protects SH-SY5Y cells from rotenone-induced cellular injury and apoptotic cell death. Celastrol also prevented the increased generation of reactive oxygen species and mitochondrial membrane potential (DeltaPsim) loss induced by rotenone. Similarly, celastrol treatment inhibited cytochrome c release, Bax/Bcl-2 ratio changes, and caspase-9/3 activation. Celastrol specifically inhibited rotenone-evoked p38 mitogen-activated protein kinase activation in SH-SY5Y cells. These data suggest that celastrol may serve as a potent agent for prevention of neurotoxin-induced neurodegeneration through multiple mechanisms and thus has therapeutic potential for the treatment of neurodegenerative diseases. PMID- 24214025 TI - Solving chemical problems with a mixture of quantum-mechanical and molecular mechanics calculations: Nobel Prize in Chemistry 2013. PMID- 24214024 TI - Origin and evolution of the eukaryotic SSU processome revealed by a comprehensive genomic analysis and implications for the origin of the nucleolus. AB - As a nucleolar complex for small-subunit (SSU) ribosomal RNA processing, SSU processome has been extensively studied mainly in Saccharomyces cerevisiae but not in diverse organisms, leaving open the question of whether it is a ubiquitous mechanism across eukaryotes and how it evolved in the course of the evolution of eukaryotes. Genome-wide survey and identification of SSU processome components showed that the majority of all 77 yeast SSU processome proteins possess homologs in almost all of the main eukaryotic lineages, and 14 of them have homologs in archaea but few in bacteria, suggesting that the complex is ubiquitous in eukaryotes, and its evolutionary history began with abundant protein homologs being present in archaea and then a fairly complete form of the complex emerged in the last eukaryotic common ancestor (LECA). Phylogenetic analysis indicated that ancient gene duplication and functional divergence of the protein components of the complex occurred frequently during the evolutionary origin of the LECA from prokaryotes. We found that such duplications not only increased the complex's components but also produced some new functional proteins involved in other nucleolar functions, such as ribosome biogenesis and even some nonnucleolar (but nuclear) proteins participating in pre-mRNA splicing, implying the evolutionary emergence of the subnuclear compartment-the nucleolus-has occurred in the LECA. Therefore, the LECA harbored not only complicated SSU processomes but also a nucleolus. Our analysis also revealed that gene duplication, innovation, and loss, caused further divergence of the complex during the divergence of eukaryotes. PMID- 24214026 TI - Neonatal immunology: responses to pathogenic microorganisms and epigenetics reveal an "immunodiverse" developmental state. AB - Neonatal animals have heightened susceptibility to infectious agents and are at increased risk for the development of allergic diseases, such as asthma. Experimental studies using animal models have been quite useful for beginning to identify the cellular and molecular mechanisms underlying these sensitivities. In particular, results from murine neonatal models indicate that developmental regulation of multiple immune cell types contributes to the typically poor responses of neonates to pathogenic microorganisms. Surprisingly, however, animal studies have also revealed that responses at mucosal surfaces in early life may be protective against primary or secondary disease. Our understanding of the molecular events underlying these processes is less well developed. Emerging evidence indicates that the functional properties of neonatal immune cells and the subsequent maturation of the immune system in ontogeny may be regulated by epigenetic phenomena. Here, we review recent findings from our group and others describing cellular responses to infection and developmentally regulated epigenetic processes in the newborn. PMID- 24214029 TI - Minimal extracorporeal circulation (MECC) does not result in less hypertrophic scar formation as compared to conventional extracorporeal circulation (CECC) with dexamethasone. AB - INTRODUCTION: Cardiopulmonary bypass surgery is associated with a systemic inflammatory response through the interaction of air, blood and synthetic components in the bypass system and the physical trauma of surgery. An alternative cardiopulmonary bypass system, minimal extracorporeal circulation (MECC), has shown promising results in terms of reducing the inflammatory response. We hypothesized that this system may reduce pathological excessive scarring. To study this assumption, the effects of MECC and the effects of conventional extracorporeal circulation (CECC) with dexamethasone on skin scarring were compared in a standardized wound-healing model. METHODS AND RESULTS: Pre-sternal scars were evaluated prospectively at four and 12 months postoperatively. The height and width of the scars were measured, using a slide caliper and sonography. The scars were scored using the validated Patient and Observer Scar Assessment Scale. Additional risk factors for hypertrophic scar formation were identified by means of a questionnaire. During surgery, MECC was used in 45 patients and CECC/dexamethasone in 42 patients. Four months postoperatively, 22 patients of the MECC group (49%) and 18 patients in the CECC/dexamethasone group (43%) had developed hypertrophic scars. Twelve months postoperatively, the hypertrophic scars in four patients of the MECC group and in two patients of the CECC/dexamethasone group had become normotrophic. In 18 patients of the MECC group (38%) and 16 patients of the CECC group (41%) the scars remained hypertrophic at 12 months. These differences between the two groups were not statistically significant. CONCLUSION: MECC does not reduce hypertrophic scar formation compared with CECC with dexamethasone, but its use is more beneficial than the use of CECC/dexamethasone because of the circulatory and immunological advantages and because treatment with dexamethasone can be omitted. PMID- 24214028 TI - Novel molecular pathways in Gorham disease: implications for treatment. AB - Rapid advances in evidence-based treatment schedules are a hallmark of modern oncology. In rare neoplastic diseases, however, clinical expertise is hard to build and evidence based on randomized trials almost impossible to collect. Gorham disease is a rare form of lymphatic proliferation accompanied by osteolysis, which usually occurs in young adults. Despite the fact that the clinical course of Gorham disease is often devastating and occasionally fatal, insights into its biological background are sparse and standardized treatment unavailable. Interestingly, recent knowledge on the mechanisms of lymphangiogenesis may help elucidate the pathophysiology of Gorham disease and lead to novel treatment targets. Here, we discuss our current understanding of Gorham disease, discuss established and emerging therapeutic strategies, and attempt to frame a treatment rationale. PMID- 24214027 TI - The IL-2/IL-2R system: from basic science to therapeutic applications to enhance immune regulation. AB - IL-2 plays a critical role in the normal function of the immune system. A trophic factor for lymphocytes, IL-2 is required for mounting and sustaining adaptive T cell responses; however, IL-2 is also critical for immune regulation via its effects on regulatory T cells (Treg cells). Over the years, we have contributed to the understanding of the biology of IL-2 and its signaling through the IL-2 receptor and helped define the key role played by IL-2 in Treg development and function. Our data show that Treg cells have a heightened sensitivity to IL-2, which may create a therapeutic window to promote immune regulation by selective stimulation of Treg cells. We are now developing new efforts to translate this knowledge to the clinical arena, through our focused interest in Type 1 diabetes as a prototypic autoimmune disease. Specifically, we aim at developing IL-2-based therapeutic regimens and incorporate means to enhance antigen-specific Treg responses, for improved and more selective regulation of islet autoimmunity. In parallel, we are pursuing studies in preclinical models of autoimmunity and transplantation to define critical factors for successful adoptive Treg therapy and develop clinically applicable therapeutic protocols. PMID- 24214030 TI - Monoclonal antibody preparation and expression profile analysis of a novel hepatoma associated gene. AB - Hepatoma associated gene (HTA), a gene screened and cloned by our previous research, was specifically expressed in certain kinds of tumors and had a cancer promoting role in hepatocellular carcinoma (HCC). To further elucidate the mechanism of HTA in hepatoma carcinogenesis and its potential role as a cancer biomarker, refolded HTA protein (HTA) was obtained by prokaryotic recombinant expression system and immobilized metal affinity chromatography. Then anti-HTA monoclonal antibody (mAb) was produced by hybridoma technique. Using the high titer anti-HTA mAb with high specificity obtained, the expression profile of HTA was analysed by immunohistochemistry staining. It showed that HTA expressed specifically in some kinds of tumors, and didn't express in almost any of the normal tissues. The positive expression rate and expression quantity of HTA was significantly higher in HCC tissues than in hepatic cirrhosis tissues, hepatic fibrosis tissues and normal hepatic tissues. The expression of HTA was positively correlated with hepatoma carcinogenic process. PMID- 24214032 TI - Linear time-of-flight mass spectrometers: Postsource pulse focusing conditions and mass scale. AB - The condition to cancel aberrations that result from initial ion velocities and length of ionization process by postsource pulse focusing in linear time-of flight mass spectrometers is derived. The ion arrival time distribution as a function of ion mass is given, which permits mass scale calibration. Simple formulas allow calculation of the voltage needed for postsource pulse focusing and the limits of the mass range where the focusing action is felt. The theory is illustrated for a specific instrument case. PMID- 24214031 TI - On the photoionization of large molecules. AB - There is no apparent limit to the size of a molecule for which photoionization can occur. It is argued that it is difficult to obtain useful photoionization mass spectra of peptides (above ~ 2000 u), proteins, and oligonucleotides, because of the high internal energy of these polar molecules as a result of the desorption event and because vibrationally excited radical cations readily fragment. Evidence to support this hypothesis is presented from the 118-nm single photon ionization (SPI) mass spectra of the cyclic decapeptide gramicidin S and of fullerenes, from null SPI results with the linear peptides substance P and gramicidin D and oligonucleotides, and from a variety of data found in the literature. The literature data include mass spectra from jet-cooled peptides, perfluorinated polyethers, collisional ionization of small neutral peptides, and the ultraviolet photoelectron spectroscopy of polymeric solids. PMID- 24214033 TI - Characterization of braun's lipoprotein and determination of its attachment sites to peptidoglycan by (252)Cf-PD and MALDI time-of-flight mass spectrometry. AB - A strategy for the characterization of bacterial lipoprotein-in this case Braun's lipoprotein (an outer membrane 7-ku lipoprotein) isolated from Escherichia coli is described by time-of-flight mass spectrometric (TOF/MS) techniques [(252)Cf plasma desorption (PD) TOF/MS and matrix-assisted laser desorption-ionization (MALDI) TOF/MS]. Covalent linkage of lipid at the N-terminal cysteine (posttranslationally modified to a S-[2,3-bis(acyloxy)-propyl]-N-acylcysteine) and, therefore, strict insolubility in aqueous solution constitute common features for this class of proteins. Relative molecular mass determination of the major molecular species of Braun's lipoprotein was obtained by selection of an appropriate mixture of organic solvents compatible with matrix/support materials useful for the mass spectrometric techniques applied. Minor components of this lipoprotein that differ only in the fatty acid composition of the lipid anchor were detected by PD TOF/MS after enzymatic release of the extremely hydrophobic N terminal amino acid followed by selective extraction with chloroform. Part of the primary sequence of this lipoprotein was confirmed based on peptide fragment ions observed in the positive ion PD mass spectra of cyanogen bromide-generated peptide fragments that had been isolated previously by reverse phase high performance liquid chromatography (HPLC). Peptidoglycan fragments that represent the attachment sites of lipoprotein to peptidoglycan were enzymatically released, separated by reverse phase HPLC, and finally characterized by time-of-flight mass spectrometric techniques ((252)Cf-PD TOF/MS, MALDI TOF/MS). The results obtained with both techniques differed only in the better sensitivity obtained with MALDI TOF/MS, which consumed a factor of 100 to 1000 less material than with PD TOF/MS. PMID- 24214034 TI - The fundamentals of applying electrospray ionization mass spectrometry to low mass poly(methyl methacrylate) polymers. AB - Electrospray ionization (ESI) is capable of ionizing many soluble polymers. The ESI spectra are complex because of overlap of the multiply charged ions of the oligomer distribution, causing current computer transform programs to fail. However, it is possible to determine the origin of the multiply charged ions, making it feasible to write a program designed to transform ESI polymer spectra. To assess the value of such a program for polymer analysis, isolated monodisperse methyl methacrylate (MMA) oligomers (25 and 50 repeat units) were used to determine molar signal response and propensity for fragmentation.The sum of the peak areas for the multiply charged MMA 50-mer was found to be only about 66% of the summed peak areas for the 25-mer for the same molar concentration. However, conversion of the multiply charged peak areas to the singly charged representations, with peak area compression taken into account, gave equal signal responses for the 25-and 50-mers. Signal response variations due to the tacticity of the MMA oligomers were not observed. Fragmentation of the MMA oligomers also was shown not to occur under normal ESI conditions. Therefore, transformation of the polymer spectra to the singly charged molecular ion distribution should allow accurate calculation of average molecular weights, polydispersity, end group mass, and repeat unit mass. PMID- 24214035 TI - Electrospray ionization mass spectrometry of biotin binding to streptavidin. AB - Stepwise binding of biotin to streptavidin via several intermediates was monitored with electrospray ionization mass spectrometry (ESIMS). Protein ligand interactions that result in conformational changes could be recognized with ESIMS by a mass shift and a change of the average multiple charge state of this protein. In addition, mass spectrometry for the ions in the gas phase revealed a much greater strength of the noncovalent bonds between the streptavidin subunits in the tetrameric complex than between the streptavidin and biotin molecules and remarkable differences in stability for the different charge states of the biotin streptavidin noncovalent complex. PMID- 24214036 TI - Isotope ratios and abundance sensitivity obtained with an inductively coupled plasma-time-of-flight mass spectrometer. AB - Isotope ratios and abundance sensitivities have been determined with an inductively coupled plasma-time-of-flight mass spectrometer (ICP-TOFMS). Abundance sensitivities are at least in the 10(6) range for low abundance ions that precede high abundance ions. Three methods of detection for isotope-ratio measurement have been compared. The three systems involve gated detection followed by analog integration, analog averaging, or ion counting. Gated ion counting offers excellent precision-between 0. 64 and 1. 00% relative standard deviation (RSD). These values approach those predicted from counting statistics and are comparable to those reported for other inductively coupled plasma-mass spectrometry (ICP-MS) instruments. In addition, a greater number of accumulated counts or longer analysis times would afford precisions of 0. 1% with stable gating electronics. The accuracy of the counting method is in the 1-10% range if no correction for mass bias is performed. However, this ion counting method suffers from a limited dynamic range due to pulse pileup. Constant-fraction discrimination gated integration and commercial boxcar averager techniques offer a broader dynamic range because of their analog nature, but the attainable RSD values are limited by drift in the detection systems and by the methods employed to calculate an accurate ratio. Overall, mass bias in the ICP-TOFMS is more severe than previous work in ICP-MS due primarily to detection system bias. PMID- 24214037 TI - Field-modulated selective ion storage in a quadrupole ion trap. AB - A new method of selective ion storage in a quadrupole ion trap is described. Broadband waveforms were applied to the endcaps of an ion trap to eject unwanted ions by resonance excitation, which enhanced the storage of selected target ions. A unique trapping field amplitude modulation technique allowed the use of waveforms with fewer frequency components. The requirements and methods of calculations for frequency-optimized wave-forms are discussed. Advantages of this method include the reduction of target ion loss that results from collision activated dissociation. In other applications, equivalent performance, relative to methods that use nonmodulated trapping fields combined with waveforms that have a higher frequency density, was shown. PMID- 24214038 TI - Ion trajectories in an electrostatic ion guide for external ion source fourier transform ion cyclotron resonance mass spectrometry. AB - An electrostatic ion guide (EIG) that consists of concentric cylinder and central wire electrodes can transport ions efficiently from an external ion source to an ion cyclotron resonance (ICR) ion trap for mass analysis, with several advantages over current injection methods. Because the electrostatic force of the EIG captures ions in a stable orbit about the wire electrode, ions with initially divergent trajectories may be redirected toward the ICR ion trap for improved ion transmission efficiency. SIMION trajectory calculations (ion kinetic energy, 1 200 eV; elevation angle, 0.30 degrees ; azimuthal angle, 0.360 degrees ) predict that ions of m/z 1000 may be transmitted through a strong (0.01 -> 3.0-T) magnetic field gradient. Judicious choice of ion source position and EIG potential minimizes the spread in ion axial kinetic energy at the ICR ion trap. Advantages of the EIG include large acceptance angle, even for ions that have large initial kinetic energy and large radial displacement with respect to the central z-axis, low ion extraction voltage (5-20 V), and efficient trapping because ions need not be accelerated to high velocity to pass through the magnetic field gradient. PMID- 24214039 TI - Peptide sequence determination from high-energy collision-induced dissociation spectra using artificial neural networks. AB - This paper reports a newly developed technique that uses artificial neural networks to aid in the automated interpretation of peptide sequence from high energy collision-induced dissociation (CID) tandem mass spectra of peptides. Two artificial neural networks classify fragment ions before the commencement of an iterative sequencing algorithm. The first neural network provides an estimation of whether fragment ions belong to 1 of 11 specific categories, whereas the second network attempts to determine to which category each ion belongs. Based upon numerical results from the two networks, the program generates an idealized spectrum that contains only a single ion type. From this simplified spectrum, the program's sequencing module, which incorporates a small rule base of fragmentation knowledge, directly generates sequences in a stepwise fashion through a high-speed iterative process. The results with this prototype algorithm, in which the neural networks were trained on a set of reference spectra, suggest that this method is a viable approach to rapid computer interpretation of peptide CID spectra. PMID- 24214040 TI - Characterization and differentiation of heterocyclic isomers. tandem mass spectrometry and molecular orbital calculations on 3-methylisoxazolo- and 2 methyloxazolopyridines. AB - Metastable mass-analyzed ion kinetic energy (MIKE) and collision-induced dissociation MIKE spectrometries have been applied to the study of all members of two classes of heteroaromatic isomers: 3-methylisoxazolo-and 2 methyloxazolopyridines. The study revealed that tandem mass spectrometry can characterize and differentiate the isomeric ion structures produced by these heterocycles. In particular, the MIKE spectra of both the molecular ions and abundant fragments formed by CO and CH3CN losses show characteristic differences that allow distinction among the isomers dependent on the position of the nitrogen atom in the pyridine ring, and distinction of isoxazole derivatives from oxazoles. The results indicate that the isomerization of the isoxazole moiety to oxazole-proposed for other analogous compounds-does not occur in these heterocyclic systems. The experimental work is supported by molecular orbital calculations both on neutral molecules and on molecular and fragment ions. PMID- 24214041 TI - The detection of intact double-stranded DNA by MALDI. AB - DNA fragments have been analyzed by matrix-assisted laser desorption ionization (MALDI) and electrospray mass spectrometry. In many cases, only the single stranded oligonucleotides have been detected. Recently, spectra of intact double stranded DNA have been obtained in both electrospray and massive cluster impact ionization. We show here the first MALDI spectra of intact double-stranded DNA (EcoR1 adaptor 12/16) that is clearly not due to nonspecific dimer formation. 6 Aza-2-thiothymine was used as the matrix in the presence of ammonium citrate. Via the same procedure but with other matrices commonly employed for oligonucleotide analysis, the intact DNA duplex was not detected. No sign of the homodimer of either of the single strands is observed. Although the spectrum also shows peaks attributable to each of the single strands, these are demonstrated to arise from the DNA solution and not the sample preparation or desorption process. PMID- 24214042 TI - Internal pulsed valve sample introduction on a quadrupole ion trap mass spectrometer. AB - A pulsed valve positioned just outside the ion trap electrodes (within the vacuum chamber) has been characterized. The observed gas pulse widths and the maximum ion intensities were found to decrease as the distance between the pulsed valve and the ion trap electrodes increased. An explanation is presented within. The pulsed valve was found to impart temporal separation in ion-molecule reactions by permitting the removal of interfering neutrals. Other factors that affect the degree of temporal separation also are presented. PMID- 24214043 TI - Thiaminase I (42 kDa) heterogeneity, sequence refinement, and active site location from high-resolution tandem mass spectrometry. AB - Thiaminase I (E.C. 2.5. 1.2) from Bacillus thiaminolyticus catalyzes the degradation of thiamin (vitamin B1). Unexpected mass heterogeneity (MW 42,127, 42,197, and 42,254; 1:2:1) in recombinant thiaminase I from Escherichia coli was detected by electrospray ionization Fourier-transform mass spectrometry, resolving power 7*10(4). Nozzle-skimmer fragmentation data reveal an extra Ala (+71.02; 71.04=theory) and GlyAla (+128.04; 128.06=theory) on the N-terminus, in addition to the fully processed enzyme. However, the fragment ion masses were consistent only with this sequence through 330 N-terminal residues; resequencing of the last 150 bps of the thiaminase I gene yields a sequence consistent with the molecular weight values and all 61 fragment ion masses. Covalently labeling the active site with a 108-Da pyrimidine moiety via mechanism-based inhibition produces a corresponding molecular weight increase in all three thiaminase I components, which indicates that they are all enzymatically active. Inspection of the fragment ions that do and do not increase by 108 Da indicates that the active site nucleophile is located between Pro(79) and Thr(177) in the 379 amino acid enzyme. PMID- 24214044 TI - Special issue to Honor Professor Fred W. McLafferty. PMID- 24214045 TI - Mass spectrometry and analytical chemistry. PMID- 24214046 TI - Scope and limitations of a general unknown screening by gas chromatography-mass spectrometry in acute poisoning. AB - The gold standard for the diagnosis of acute poisoning is toxicological analysis. Because information on the incorporated toxic substance provided by the patient or his relatives is known from experience to be unreliable in about 40% of all intoxications, a screening procedure that covers most relevant drugs and toxicants is required rather than an analytical procedure optimized for the identification of a single class of substances. The special task for a general unknown screening procedure is to identify a toxic substance among endogenous or food-derived substances as well as environmental toxicants in a biological matrix on an emergency basis. Because the unknown toxic substance may vary considerably in its physicochemical properties and its concentration range, a universally applicable screening procedure is required. Although gas chromatography-mass spectrometry has been used for three decades, it still offers many unique advantages in terms of sensitivity, specificity, reliability, and coverage of a large number of toxic substances. Because the procedure has to be kept as simple and as short as possible, compromises have to be made with respect to extraction, derivatization, and mass-spectral techniques. The specimen of choice for a general unknown screening is-if available-urine. The standard mode of ionization is electron impact. The identification of unknown substances is highly challenging because, in our experience, previously unknown metabolites may be detected rather frequently in acute poisoning. Although an automated mass spectra library search considerably facilitates the identification process, expert knowledge on the identification of substances not included in the library as well as knowledge in clinical toxicology and metabolism is indispensable. PMID- 24214047 TI - Hydrogen bonding in transient bifunctional hypervalent radicals by neutralization reionization mass spectrometry. AB - Neutralization-reionization mass spectrometry is used to generate hypervalent 9-N 4 (ammonium) and 9-O-3 (oxonium) radicals derived from protonated alpha,omega-bis (dimethylamino)alkanes and alpha,omega-dimethoxyalkanes, which exist as cyclic hydrogen-bonded structures in the gas phase. Collisional neutralization with dimethyl disulfide, trimethylamine, and xenon of the hydrogen-bonded onium cations followed by reionization with oxygen results in complete dissociation. Bond cleavages at the hypervalent nitrogen atoms are found to follow the order CH2-N>CH3-N>N-H, which differs from that in the monofunctional hydrogen-n heptyldimethylammonium radical, which gives CH2-N>N-H>CH3-N. No overall stabilization through hydrogen bonding of the bifunctional hypervalent ammonium and oxonium radicals is observed. Subtle effects of ring size are found that tend to stabilize large ring structures and are attributed to intramolecular hydrogen bonding. PMID- 24214048 TI - Reactivity of collisionally activated dichlorocarbene dications studied by tandem mass spectrometry. AB - The dissociation mechanisms of dichlorocarbene dications following collisional activation have been investigated via tandem mass spectrometric techniques and semi-empirical calculations. Three channels appear to be significant: {fx1019-1} The second channel becomes dominant at high internal energy. Production of ground state fragments (channel 1) involves a transition driven by spin-orbit coupling from the CCl 2 (2+) [Formula: see text] state to the CCl 2 (2-) a(3)Sigma u (-) state en route to the fragments. The dissociation barrier for the production of ground state fragments from the ground electronic state of CCl 2 (2+) via the spin-orbit-induced transition is equal to 420 kJ mol(-1). The dissociation pathway that corresponds to channel 3 includes a first isomerization step from the linear Cl-C-Cl(2+) structure to a bent Cl-Cl-C(2+) connectivity. The calculated isomerization barrier amounts to 550 kJ mol(-1). The calculated reverse activation barriers are compatible with the measured kinetic energy released on the fragments. PMID- 24214049 TI - Characterization of the C3H 6O (+.) ion from 2-methoxyethanol. Mixture analysis by dissociation and neutralization-reionization. AB - The C3H6O(+.) ion formed upon the dissociative ionization of 2-methoxyethanol is identified by a combination of several tandem mass spectrometry methods, including metastable ion (MI) characteristics, collisionally activated dissociation (CAD), and neutralization-reionization mass spectrometry (NRMS). The experimental data conclusively show that 2-methoxyethanol molecular ion, namely, HOCH2CH2OCH 3 (+.) , loses H2O to yield mainly the distonic radical ion .CH2CH2OCH 2 (+) along with a smaller amount of ionized methyl vinyl ether, namely, CH2=CHOCH 3 (+.) . Ring-closed products, such as the oxetane or the propylene oxide ion are not observed. The proportion of .CH2CH2OCH 2 (+) increases with decreasing internal energy of the 2-methoxyethanol ion, which indicates a lower critical energy for the pathway leading to this product than for the competitive generation of CH2=CHOCH 3 (+.) . The present study also uses MI, CAD, and NRMS data to assess the structure of the distonic ion(+) (CH3)CHOCH2. (ring-opened ionized propylene oxide) and evaluate its isomerization proclivity toward the methyl vinyl ether ion. PMID- 24214050 TI - Preference for an ion-neutral complex-mediated pathway over a five-membered-ring H shift in the isomerization of CH3O (+)HCH 2CH 2 (.) to CH 3CH 2CH 2OH (+.) by Ab initio theory. AB - Ab initio theory is used to explore whether the path from CH3OH(+)CH2CH 2 (.) (1) to CH3CH2CH2OH(+.) (5) goes by way of a conventional 1,4-H shift to form .CH2OH(+)CH2CH3 (2), or via the ion-neutral complex-mediated H transfer [CH3OHCH2=CH2](+.) (3) -> [CH3CH 2 (.) CH2OH(+)] (4). Five levels of theory all place the highest energy point in the complex-mediated reaction 3 -> 4 slightly below that for the 1,4-H shift 1 -> 2, but both routes appear energetically feasible near the threshold for the dissociation of 1 to CH3CH2 + CH2=OH(+). Thus, 1 may take both paths to 5. It is concluded that when both a conventional and a complex-mediated pathway seem plausible in a given system, the latter should be considered to be as likely as the former. Ab initio descriptions of other species involved in the isomerization of 1 to 2 also are presented. PMID- 24214051 TI - Organic ion imaging beyond the limit of static secondary ion mass spectrometry. AB - Secondary ion mass spectra and images were obtained from spikes of choline chloride, acetylcholine chloride, and methylphenylpyridinium iodide deposited onto specimens of porcine brain tissue. Samples were subsequently subjected to a dose of 10-keV Cs(+) sufficient to suppress secondary ion emission characteristic of the targeted analytes. Following ablation of the samples by massive glycerol clusters generated by electrohydrodynamic emission, secondary ion mass spectra and images could be obtained that reflected the identity and location of the spiked analytes. The absolute intensity of secondary ion emission that followed ablation was found to be between 30 and 100% of the intensity obtained prior to exposure to the high dose of Cs'. Not all chemical noise is removed by ablation, however, so that the signal-to-noise ratios after ablation correspond to between 10 and 85% of their values observed under conditions of low primary ion dose. PMID- 24214052 TI - Multiphoton ionization of molecules: A comparison between femtosecond and nanosecond laser pulse ionization efficiency. AB - Multiphoton ionization mass spectra of nonvolatile molecules laser desorbed into a supersonic beam are recorded. It is shown by indirect measurements that the laser desorption of neutrals is not mass limited, but lead to the formation of neutrals with intesities large enough for intense signals. To investigate the efficiency of the multiphoton ionization process with varying laser pulse durations, simultaneous laser pulses of 500 fs and 5 ns or 100 fs and 5 ns have been applied to the neutral beam. The energies of both femtosecond and nanosecond laser pulses are held in a comparable magnitude, and thus produce, in the resulting ion intensity, very large differences up to 4 orders of magnitude. For larger evaporated molecules (> 500 u) the ionization efficiency from nanosecond laser pulses drops significantly in comparison to femtosecond laser pulse excitation. A variety of possible reasons for the different ionization and dissociation behavior in femtosecond and nanosecond laser pulse excitations are discussed in this paper. It is rationalized that even with very short laser pulses and large molecules the "ladder switching model" for ionization and fragmentation is valid. PMID- 24214053 TI - An investigation of the energetics of peptide ion dissociation by laser desorption chemical ionization fourier transform mass spectrometry. AB - The energy dependence of competing fragmentation pathways of protonated peptide molecules is studied via laser desorption-chemical ionization in a Fourier transform ion cyclotron resonance spectrometer. Neutral peptide molecules are desorbed by the technique of substrate-assisted laser desorption, followed by post-ionization with a proton transfer reagent ion species. The chemical ionization reaction activates the protonated peptide molecules, which then fragment in accordance with the amount of excess energy that is deposited. Chemical ionization forms a protonated molecule with a narrower distribution of activation energy than can be formed by activation methods such as collision activated dissociation. Furthermore, the upper limit of the activation energy is well defined and is approximately given by the enthalpy of the chemical ionization reaction. Control over the fragmentation of peptide ions is demonstrated through reactions between desorbed peptide molecules with different reagent ion species. The fragmentation behavior of peptide ions with different internal energies is established by generation of a breakdown curve for the peptide under investigation. Breakdown curves are reported for the peptides Val Pro, Val-Pro-Leu, Phe-Phe-Gly-Leu-Met NH2, and Arg-Lys-Asp-Val-Tyr. The derived breakdown curve of Val-Pro has been fitted by using quasi-equilibrium Rice Ramsperger-Kassel-Marcus theory to model the unimolecular dissociation of the protonated peptide to provide a better understanding of the mechanisms for the formation of fragment ions that originate from protonated peptides. PMID- 24214054 TI - Influences of peptide side chains on the metal ion binding site in metal ion cationized peptides: Participation of aromatic rings in metal chelation. AB - Aromatic side chains on amino acids influence the fragmentations of cationic complexes of doubly charged metal ions and singly deprotonated peptides. The metal ion interacts with an aromatic side chain and binds to adjacent amide nitrogens. When fragmentation occurs, this bonding leads to the formation of abundant metal-containing a-type ions by reactions that occur at the sites of amino acids that contain the aromatic side chain. Furthermore, formation of metal containing immonium ions of the amino acids that contain the aromatic side chain also are formed. The abundant a-type ions may be useful in interpretation strategies in which it is necessary to locate in a peptide the position of an amino acid that bears an aromatic side chain. PMID- 24214055 TI - On the maximum charge state and proton transfer reactivity of peptide and protein ions formed by electrospray ionization. AB - A relatively simple model for calculation of the energetics of gas-phase proton transfer reactions and the maximum charge state of multiply protonated ions formed by electrospray ionization is presented. This model is based on estimates of the intrinsic proton transfer reactivity of sites of protonation and point charge Coulomb interactions. From this model, apparent gas-phase basicities (GB(app)) of multiply protonated ions are calculated. Comparison of this value to the gas-phase basicity of the solvent from which an ion is formed enables a maximum charge state to be calculated. For 13 commonly electrosprayed proteins, our calculated maximum charge states are within an average of 6% of the experimental values reported in the literature. This indicates that the maximum charge state for proteins is determined by their gas-phase reactivity. Similar results are observed for peptides with many basic residues. For peptides with few basic residues, we find that the maximum charge state is better correlated to the charge state in solution. For low charge state ions, we find that the most basic sites Arg, Lys, and His are preferentially protonated. A significant fraction of the less basic residues Pro, Trp, and Gln are protonated in high charge state ions. The calculated GB(app) of individual protonation sites varies dramatically in the high charge state ions. From these values, we calculate a reduced cross section for proton transfer reactivity that is significantly lower than the Langevin collision frequency when the GB(app) of the ion is approximately equal to the GB of the neutral base. PMID- 24214056 TI - Applying charge discrimination with electrospray ionization-mass spectrometry to protein analyses. AB - Electrospray ionization with a magnetic sector mass spectrometer and scanning array detector has unique advantages for sensitive analyses of large biomolecules. The ability to discriminate against low charge state ions (smaller peptides, buffers and salts, background ions) allows for detection of more highly charged ions from proteins present at much lower concentration relative to the small ions from buffers and detergents present. Low femtomole detection limits can be achieved for proteins greater than 100 ku. The charge discrimination phenomenon is more pronounced for higher charged ions, and especially for large biomolecules. Although the charge distribution for the monomer (66 ku) and dimer (133 ku) species of bovine serum albumin overlap, both species can be ascertained readily in a mixture because the lower charged monomer ions have higher optimum microchannel plate voltages than the higher charged dimer ions. Protein containing solutions can be analyzed directly by electrospray ionization-mass spectrometry (ESI-MS) with array detection, which eliminates time-consuming separation and sample cleanup procedures. For example, heme-containing proteins can be directly detected from ESI-MS of human blood (hemoglobin) as well as from raw meat juices (hemoglobin and myoglobin). PMID- 24214057 TI - Study of noncovalent enzyme-inhibitor complexes and metal binding stoichiometry of matrilysin by electrospray ionization mass spectrometry. AB - Electrospray ionization mass spectrometry (ESI-MS) was used to study the noncovalent metallo-enzyme-inhibitor complexes of matrilysin (a matrix metalloproteinase of mass 18,720 u) under gentle experimental conditions and to determine the metal ion association stoichiometries in both the free enzyme and the complexes. The metal association stoichiometries of the free matrilysin were found to be highly sensitive to solution pH changes. At pH 2.2 the enzyme existed as metal-free apo-matrilysin and was not capable of binding an inhibitor. At pH 4.5-7.0 the enzyme associated specifically with zinc and calcium cations and became active in inhibitor binding. Although the stoichiometries of the metal cofactors varied (zero to two zinc and/or calcium ions) in the free enzyme dependent on solution pH, the predominant form of the enzyme-inhibitor complexes in the pH range of 4.5-7.0, in contrast, always had the metal association stoichiometry of 2Zn + 2Ca, which was the same stoichiometry the most active free metallo-enzyme had at the optimal pH of 7. At the activity onset pH of 4.5 matrilysin existed mostly as apo-enzyme (but in a conformation different from the denatured one at pH 2.2) and bound to an inhibitor slowly (time constant ~ 2.5 min) to form the noncovalent metallo-enzyme-inhibitor complex. Of the two inhibitors studied, the one with the higher solution binding constant also produced larger ion signals for the noncovalent complex in the solvent-free gas phase, which pointed to the feasibility of the use of ESI-MS for inhibitor screening studies. PMID- 24214058 TI - The computer-assisted interpretation of copolymer mass spectra. AB - A computer program called MSCOPOL has been developed to aid in the interpretation of copolymer mass spectra. The program reads the mass spectrum, calculates the most likely monomer masses via correlation or Fourier transform methods, determines possible end group masses based on the monomer masses, and can then search monomer and end group data bases for likely chemical moieties. Refinement of the end group result is possible by calculation of the monomer ratio and degree of polymerization as a function of end group mass. The program is written in Microsoft Visual Basic and runs on an IBM compatible PC. Applications are shown for polystyrene, poly(N-vinyl pyrrolidone/vinyl acetate), and poly(ethylene oxide/propylene oxide). PMID- 24214059 TI - Determination of pesticides in aqueous samples by solid-phase microextraction in line coupled to gas chromatography-mass spectrometry. AB - A multiresidue method was developed for the determination of nitrogen- and phosphorous-containing pesticides (amines, anilides, phosphorothioates, and triazines) by solid-phase microextraction (SPME) in-line coupled to gas chromatography-mass spectrometry (GC/MS). The 85-um polyacrylate fiber was first dipped into the aqueous sample for a given time and then directly introduced into the heated injector of the gas chromatography-mass spectrometer, where the analytes are thermally desorbed. The method was evaluated with respect to the limit of detection, linearity, and precision. The limit of detection [selected ion monitoring (SIM) mode] depends on the compound and varies from 5 to 90 ng/L. The method is linear over at least 3 orders of magnitude with coefficients of correlation usually >=0.996. In general, the coefficient of variation (precision) is <10%. The partitioning of the analyte between the aqueous phase and the polymeric phase depends on the hydrophobicity of the compound as expressed by the octanol-water partitioning coefficient P ow. The addition of sodium chloride has a strong effect on the extraction efficiency. This effect increases with decreasing hydrophobicity (increasing polarity) of the compound.The triazines atrazine, simazine, and terbuthylazine were first identified and quantified in water samples from the effluent of sewage plants by SPME-gas chromatography nitrogen-phosphorus detection (GC/NPD). For such a complex matrix GC/NPD is not sufficiently selective for an unambiguous identification at low levels (<1 ppb) of pesticides. Selectivity may be enhanced by using SMPE-GC/MS in the SIM mode with three characteristic ions for each pesticide. This method allows an unequivocal identification and quantification at low levels of pesticides in environmental samples.At a target limit of detection below 100 ng/L, SPME-GC/MS represents a very simple, fast, selective, and solvent-free multimethod for the extraction and determination of these nitrogen- and phosphorous-containing pesticides from aqueous samples. PMID- 24214061 TI - An appreciation of Fred McLafferty. PMID- 24214064 TI - Gas-phase stability of cluster ions SF m (+) (SF 6) n with m = 0-5 and n = 1-3. AB - The gas-phase stabilities of cluster ions SF m (+) (SF6) n with m = 0-5 were determined by using a high pressure mass spectrometer. The bond energies of SF m (+) (SF6)1 were found to be less than 10 kcal/mol and to decrease with m = 0 -> 5. There appear to be rather large gaps in the bond energies between n = 1 and 2 for the clusters SF m (+) (SF6) n with m = 0-4. The structures of SF 5 (+) , SF(+) (SF6)1 SF 3 (+) (SF6)1 and SF 5 (+) (SF6)1, were investigated by ab initio molecular orbital calculations. For SF 5 (+) , the D 3h geometry is found to be most stable and C 4v is a transition state of the Berry pseudorotation. For the ion-molecule complexes, the "on-top hat" models were found to be the most stable structures. PMID- 24214062 TI - A novel single-trial event-related potential estimation method based on compressed sensing. AB - Cognitive functions are often studied using event-related potentials (ERPs) that are usually estimated by an averaging algorithm. Clearly, estimation of single trial ERPs can provide researchers with many more details of cognitive activity than the averaging algorithm. A novel method to estimate single-trial ERPs is proposed in this paper. This method includes two key ideas. First, singular value decomposition was used to construct a matrix, which mapped single-trial electroencephalographic recordings (EEG) into a low-dimensional vector that contained little information from the spontaneous EEG. Second, we used the theory of compressed sensing to build a procedure to restore single-trial ERPs from this low-dimensional vector. ERPs are sparse or approximately sparse in the frequency domain. This fact allowed us to use the theory of compressed sensing. We verified this method in simulated and real data. Our method and dVCA (differentially variable component analysis), another method of single-trial ERPs estimation, were both used to estimate single-trial ERPs from the same simulated data. Results demonstrated that our method significantly outperforms dVCA under various conditions of signal-to-noise ratio. Moreover, the single-trial ERPs estimated from the real data by our method are statistically consistent with the theories of cognitive science. PMID- 24214065 TI - The structure of C5H 5RFe (+) (R = F, Cl, Br, I, O, OH, OCH3, C 6H 5, H) ions in the gas phase and the generation of their neutral counterparts by neutralization reionization mass spectrometry. AB - The structure of C5H5FeR(+.) ions was studied by tandem mass spectromerry that included the neutralization-reionization (NR) method. Halogen-containing species (R = F, Cl, Br, I) showed fragmentation that was consistent with a structure that has the cyclopentadienyl ring and R as separate ligands at the metal atom (structure A). This structure also was identified for C5H5FeO(+) and CpFeOH(+.) ions, but these species also easily isomerized to metal-cyclopentadiene structure, RC5H5Fe(+.) (B), followed by hydrogen rearrangement(s) and CO loss. B was the dominant structure of C5H5FeH(+.) and C5H5FeC6H 5 (+.) ions. All ions that have structure A showed recovery signals in their NR mass spectra that indicated that their stable neutral counterparts were generated. The NR mass spectra also provided complementary information about the structure of ions before neutralization and after reionization. PMID- 24214063 TI - Acyl-lipid thioesterase1-4 from Arabidopsis thaliana form a novel family of fatty acyl-acyl carrier protein thioesterases with divergent expression patterns and substrate specificities. AB - Hydrolysis of fatty acyl thioester bonds by thioesterases to produce free fatty acids is important for dictating the diversity of lipid metabolites produced in plants. We have characterized a four-member family of fatty acyl thioesterases from Arabidopsis thaliana, which we have called acyl-lipid thioesterase1 (ALT1), ALT2, ALT3, and ALT4. The ALTs belong to the Hotdog fold superfamily of thioesterases. ALT-like genes are present in diverse plant taxa, including dicots, monocots, lycophytes, and microalgae. The four Arabidopsis ALT genes were found to have distinct gene expression profiles with respect to each other. ALT1 was expressed specifically in stem epidermal cells and flower petals. ALT2 was expressed specifically in root endodermal and peridermal cells as well as in stem lateral organ boundary cells. ALT3 was ubiquitously expressed in aerial and root tissues and at much higher levels than the other ALTs. ALT4 expression was restricted to anthers. All four proteins were localized in plastids via an N terminal targeting sequence of about 48 amino acids. When expressed in Escherichia coli, the ALT proteins used endogenous fatty acyl-acyl carrier protein substrates to generate fatty acids that varied in chain length (C6-C18), degree of saturation (saturated and monounsaturated), and oxidation state (fully reduced and beta-ketofatty acids). Despite their high amino acid sequence identities, each enzyme produced a different profile of lipids in E. coli. The biological roles of these proteins are unknown, but they potentially generate volatile lipid metabolites that have previously not been reported in Arabidopsis. PMID- 24214066 TI - Characterization of noncovalent complexes formed between minor groove binding molecules and duplex DNA by electrospray ionization-mass spectrometry. AB - The noncovalent complex formed in solution between minor groove binding molecules and an oligonucleotide duplex was investigated by electrospray ionization-mass spectrometry (ESI-MS). The oligonucleotide duplex formed between two sequence specific 14-base pair oligonucleotides was observed intact by ESI-MS and in relatively high abundance compared to the individual single-stranded components. Only sequence-specific A:B duplexes were observed, with no evidence of random nonspecific aggregation (i.e., A:A or B:B) occurring under the conditions utilized. Due to the different molecular weights of the two 14-base pair oligonucleotides, unambiguous determination of each oligonucleotide and the sequence-specific duplex was confirmed through their detection at unique mass-to charge ratios. The noncovalent complexes formed between the self-complementary 5' dCGCAAATTTGCG-3' oligonucleotide and three minor groove binding molecules (distamycin A, pentamidine, and Hoechst 33258) were also observed. Variation of several electrospray ionization interface parameters as well as collision-induced dissociation methods were utilized to characterize the nature and stability of the noncovalent complexes. The noncovalent complexes upon collisional activation dissociated into single-stranded oligonucleotides and single-stranded oligonucleotides associated with a minor groove binding molecule. ESI-MS shows potential for the study of small molecule-oligonucleotide duplex interactions and determination of small molecule binding stoichiometry. PMID- 24214067 TI - Why Are B ions stable species in peptide spectra? AB - Protonated amino acids and derivatives RCH(NH2)C(+O)X . H(+) (X = OH, NH2, OCH3) do not form stable acylium ions on loss of HX, but rather the acylium ion eliminates CO to form the immonium ion RCH = NH 2 (+) . By contrast, protonated dipeptide derivatives H2NCH(R)C(+O)NHCH(R')C(+O)X . H(+) [X = OH, OCH3, NH2, NHCH(R")COOH] form stable B2 ions by elimination of HX. These B2 ions fragment on the metastable ion time scale by elimination of CO with substantial kinetic energy release (T 1/2 = 0.3-0.5 eV). Similarly, protonated N-acetyl amino acid derivatives CH3C(+O)NHCH(R')C(+O)X . H(+) [X = OH, OCH3, NH2, NHCH(R")COOH] form stable B ions by loss of HX. These B ions also fragment unimolecularly by loss of CO with T 1/2 values of ~ 0.5 eV. These large kinetic energy releases indicate that a stable configuration of the B ions fragments by way of activation to a reacting configuration that is higher in energy than the products, and some of the fragmentation exothermicity of the final step is partitioned into kinetic energy of the separating fragments. We conclude that the stable configuration is a protonated oxazolone, which is formed by interaction of the developing charge (as HX is lost) with the N-terminus carbonyl group and that the reacting configuration is the acyclic acylium ion. This conclusion is supported by the similar fragmentation behavior of protonated 2-phenyl-5-oxazolone and the B ion derived by loss of H-Gly-OH from protonated C6H5C(+O)-Gly-Gly-OH. In addition, ab initio calculations on the simplest B ion, nominally HC(+O)NHCH2CO(+), show that the lowest energy structure is the protonated oxazolone. The acyclic acylium isomer is 1.49 eV higher in energy than the protonated oxazolone and 0.88 eV higher in energy than the fragmentation products, HC(+O)N(+)H = CH2 + CO, which is consistent with the kinetic energy releases measured. PMID- 24214068 TI - Mass and charge state assignment for proteins and peptide mixtures via noncovalent adduction in electrospray mass spectrometry. AB - A method has been developed that takes advantage of the formation of noncovalent compounds in electrospray mass spectrometry. Mixtures of proteins and peptides are shown to produce an intense ion that corresponds to a 1:1 complex with a crown ether (18-crown-6). Although the crown ether may be added directly to the solution, for the current experiments it is introduced via the methanol liquid sheath. The spacing of these complexed species in the mass spectrum allows unambiguous determination of the charge state of the ions and their actual mass. Through constant neutral loss scans, charge state may be determined, mass assigned, spectra simplified, and chemical noise may be reduced for the analysis of complex peptide samples without Chromatographic separation. Finally, the prevalence of single complexation permits mass assignments based on the mass difference of a single protein ion and its complexed form at any charge state. In essence, the method performs a separation based on charge state. It can be used to complement Chromatographic separation and deconvolution algorithms for the electrospray mass spectrometry analysis of peptide-protein mixtures. PMID- 24214069 TI - Charge state distribution shifting of protein ions observed in matrix-assisted laser desorption ionization mass spectrometry. AB - By using a new sample preparation method for matrix-assisted laser desorption ionization, a significant shift to lower mass-to-charge values can be obtained for many protein samples. The sample preparation technique involves the creation of a thin film of protein-doped alpha-cyano-4-hydroxycinnamic acid (CHCA) matrix formed in the presence of glycerol on top of a previously deposited pad of CHCA matrix. The higher charge states were not observed if the laser power was significantly above the threshold needed to produce protein molecular ions. Similar spectra were observed when samples were prepared in the presence of urea. The phenomenon was specific for the CHCA matrix because no effects were observed when sinapinic acid (3,5-dimethoxy-4-hydroxy-trans-cinnamic acid) and 2-(4 hydroxyphenylazo) benzoic acid matrices were used with the new sample preparation method. PMID- 24214070 TI - Analysis of lipid hydroperoxides and long-chain conjugated keto acids by negative ion electrospray mass spectrometry. AB - Lipid hydroperoxides are important products of enzymatic processes and autooxidation products of polyunsaturated fatty acids. Analysis of such compounds has proved difficult in the past, but negative ion electrospray ionization mass spectrometry was found to be suitable for direct analysis. Abundant [M - H](-) ions were observed in full scan mode for hydroper-oxyeicosatetraenoic (HPETE), hydroperoxyoctadecenoic acid isomers, and 5,12-diHPETE. Loss of water was observed for all species. Collisional activation and tandem mass spectrometry generated unique and characteristic spectra that shared some common features such as loss of small neutral molecules. More importantly, fragment ions that were indicative of the position of the hydroperoxide were observed. Collision-induced decomposition (CID) of [M - H2O](-) for the HPETE isomers was found to be virtually identical to the CID mass spectra of the [M - H](-) anions from corresponding keto-eicosatetraenoic acids, which suggests that the hydroperoxide anions decompose via a dehydration intermediate that resembles the keto acid molecular anion. Cleavage of the double bond allylic to the hydroperoxide formed structurally characteristic ions at m/z 129 from 5-HPETE, m/z 153 from 12-HPETE, and m/z 113 from 15-HPETE. Charge-driven allylic fragmentation led to formation of m/z 203 from 5-HPETE, m/z 179 from 12-HPETE, and m/z 219 from 15-HPETE. Mechanisms consistent with the decomposition of stable isotope analogues are proposed for the formation of these and other characteristic ions. These specific decompositions can be used in multiple reaction monitoring to measure picomolar concentrations of hydroperoxides by direct high performance liquid chromatography tandem mass spectrometry. PMID- 24214071 TI - Structural determination of picomole amounts of phospholipids via electrospray ionization tandem mass spectrometry. AB - The remarkable sensitivity of electrospray ionization was exploited to achieve great increases in the sensitivity of tandem mass spectrometric analyses of phospholipids derived from both synthetic and biologic sources. Herein, we demonstrate that (1) product-ion spectra after electrospray ionization can be obtained easily by utilizing <= 5 pmol of phospholipid with a mass-selected window of less than 2 mass units, (2) the low energy inherent in the electrospray ionization method facilitates analysis of labile molecular ions that are not easily detected with the relatively high energy employed during fast-atom bombardment desorption, and (3) collision-induced dissociation of precursor ions generated from electrospray ionization often resulted in novel product-ion patterns. Collectively, these results underscore the utility of electrospray ionization tandem mass spectroscopy for the structural determination of diminutive amounts of phospholipids. PMID- 24214072 TI - An electrospray ionization study of some novel alkylamine thiohydantoin amino acid derivatives. AB - An electrospray ionization-mass spectrometric (ES-MS) study of some novel alkylamine thiohydantoin amino acid derivatives is presented. The alkylamine derivatives are being developed as part of an on-going effort to couple an Edmanlike protein sequencer to a bench-top electrospray ionization (ES) mass spectrometer. The ES-MS and capillary-skimmer collision-induced dissociation (CID) mass spectra of eight dimethylaminopropylthiohydantoin (DMAP-TH) amino acid derivatives as well as the trimethylaminopropylthiohydantoin (TMAP-TH), diethylaminopropylthiohydantoin, and dibutylaminopropylthiohydantoin (DBAP-TH) derivatives of Phe are presented. The spectra contain prominent [M + H](+) ions as well as fragment ions due to the loss of the respective neutral alkylamines. The CID spectrum of DMAP-TH-Phe also contains the dibutylaminoethyl cation. The relative responses of the alkylamine thiohydantoin derivatives obtained under identical solvent conditions are found to increase as the solvophobicity of the amino acid R group increases; the most solvophobic DBAP-TH-Phe gives rise to the highest overall response. DMAP-TH-Phe and the quaternary amine derivative TMAP-TH Phe have comparable sensitivities when a sufficiently acidic solvent (pH = 3) is employed. Implications of these studies in the coupling of a protein sequencer to an ES mass spectrometer are discussed as are the requisite modifications of a single quadrupole mass spectrometer for ES analyses. PMID- 24214073 TI - Signal enhancement for gradient reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol. AB - Trifluoroacetic acid (TFA) and other volatile strong acids, used as modifiers in reverse-phase high-performance liquid chromatography, cause signal suppression for basic compounds when analyzed by electrospray ionization mass spectrometry (ESI-MS). Evidence is presented that signal suppression is caused by strong ion pairing between the TFA anion and the protonated sample cation of basic sample molecules. The ion-pairing process "masks" the protonated sample cations from the ESI-MS electric fields by rendering them "neutral. " Weakly basic molecules are not suppressed by this process. The TFA signal suppression effect is independent from the well-known spray problem that electrospray has with highly aqueous solutions that contain TFA. This previously reported spray problem is caused by the high conductivity and surface tension of aqueous TFA solutions. A practical method to enhance the signal for most basic analytes in the presence of signal suppressing volatile strong acids has been developed. The method employs postcolumn addition of a solution of 75% propionic acid and 25% isopropanol in a ratio 1:2 to the column flow. Signal enhancement is typically 10-50 times for peptides and other small basic molecules. Thus, peptide maps that use ESI-MS for detection can be performed at lower levels, with conventional columns, without the need to use capillary chromatography or reduced mass spectral resolution to achieve satisfactory sensitivity. The method may be used with similar results for heptafluorobutyric acid and hydrochloric acid. A mechanism for TFA signal suppression and signal enhancement by the foregoing method, is proposed. PMID- 24214074 TI - Iron carboxylate oxygen-centered-triangle complexes detected during electrospray use of organic acid modifiers with a comment on the finnigan TSQ-700 electrospray inlet system. AB - Use of infusion methods rather than high-performance liquid chromatography allowed us to confirm the observation that solutions of propionic acid isopropanol restore sensitivity lost due to trifluoroacetic acid in electrospray mass spectra of basic substances, particularly peptides. In this work, when propionic acid-isopropanol was used, we detected an abundant ion with m/z 622 that shifted to m/z 538 when we substituted acetic acid-methanol for the propionic acid-isopropanol. Via accurate mass measurement and tandem mass spectrometry the origin of the ion was identified as the complex Fe3O(O2CR)6(L)0 3, where L is one of several ligands from solvent or water. The grounding arrangement of the Finnigan TSQ-700 electrospray source produces electrolytic currents that may accentuate the abundance of this complex and specifically produces observable gas bubbles that adversely affect the spray stability. PMID- 24214075 TI - How to measure the kinetic energy distribution of the precursor ion main beam in mass-analyzed ion kinetic energy spectrometry experiments. AB - Scans of the electrostatic analyzer (ESA) across the precursor ion beam in reverse-geometry (BE) mass spectrometers that are operated under double-focusing conditions do not measure the "energy resolution of the main beam": They only measure double-focusing resolution. The only way that ESA scans can measure the kinetic energy distribution of the main beam is to operate the instrument so that angular (directional) focusing is not achieved. Thus, the mass spectrometer is no longer double-focusing. Under double-focusing conditions, however, scans of the accelerating voltage while the magnetic field and ESA are held constant can be used to measure either the kinetic energy distribution of the main beam that enters the magnet or the energy-resolving power of the instrument. Scans at a constant ratio of B(2)/E can be used similarly. The energy-resolving power of any ESA is defined by its dispersion and the widths of the energy-resolving object and image slits that immediately precede and follow the ESA, respectively. The use of BE, EB, and triple-sector instruments to measure energy-resolving power and the kinetic energy distribution of the precursor ion main beam is compared and discussed. PMID- 24214076 TI - Unsuitability of (12)C 60 as a standard of atomic weight. AB - A critical discussion is given of the suggestion by Dougherty et al. (J. Am. Soc. Mass Spectrom. 1994, 5, 120) that the (12)C60 molecule replace the (12)C atom as the primary standard of atomic mass. Adoption of the proposed standard would require that the unified atomic weight/mass scale, finally achieved with much difficulty in 1960, be abandoned without demonstrable benefit. Furthermore, the proposed standard has a molecular mass that is inherently ambiguous at a level that makes it unacceptable for that purpose. PMID- 24214077 TI - The complexation of protonated peptides with saccharides in the gas phase decreases the rates of hydrogen/deuterium exchange reactions. AB - Gas-phase noncovalently bound complexes are probed by hydrogen/deuterium exchange. The complexes, composed of a protonated amino acid and a monosaccharide, are investigated to observe the effects of complexation on the rates of exchange. Rate constants are determined and compared for complexed and uncomplexed amino acids. The overall rate constant, which corresponds to exchange of a specific number of hydrogens, is deconvoluted to yield site-specific rate constants. Complexation of amino acids with saccharides significantly decreases the rate constants of the exchange. Results of molecular orbital calculations are provided to explain the decrease in the rates. PMID- 24214078 TI - Observation of alkali-metal-carboxylate radical anions in fast-atom bombardment. AB - The existence of a series of 32 molecular radical anions from carboxylic acids salts RCOO-Cat(-), where R = CH3, CH3CH2, CH3CH2CH2, (CH3)2CH, C6H5, o-CH3-C6H4, m-CH3-C6H4, and p-CH3-C6H4 and Cat = Li, Na, K, Rb, has been proven by the observation of their fragmentation in negative-ion fast-atom bombardment tandem mass spectrometry. These species occur at very low abundance and are not detected in the fast-atom bombardment spectra because they are hidden in the background. However, the collision-induced dissociation fragmentation of ions selected at the mass-to-charge ratio values that correspond to these species display characteristic signals that are completely different from the signals observed from pure matrix or after addition of corresponding metal hydroxide to the matrix. The main fragmentation observed is the loss of the neutral metal atom from RCOOCat(-.), followed by a loss of CO2 for the aromatic compounds. Neutral loss experiments also confirm the existence of these radical anions. Scans for the loss of a selected metal after addition of one of the carboxylic acid salts to the matrix display abundant peaks at mass-to-charge ratio values that correspond to the salt radical anions. Some weaker peaks appear at other mass-to charge ratio values independent of the salt that is used and also are observed from the matrix when the corresponding metal hydroxide is added. When alkali metal salts from some deuterated acids are analyzed, the predicted shifts are observed. The loss of the neutral metal is more pronounced from RCOONa(-.), RCOOK(-.), and RCOORb(-.) than from RCOOLi(-.). PMID- 24214080 TI - The 8th Sanibel conference. PMID- 24214079 TI - Design and performance of a high resolution electrospray ion source for a magnetic sector mass spectrometer with a heated capillary inlet. AB - The design and performance of an electrospray ion source for a high resolution magnetic sector mass spectrometer that utilizes a heated capillary has been presented. Low pressure, high sensitivity, stable electrospray, low flow rates, and low electronic noise were important factors in achieving high resolution electrospray mass spectrometry. A unit mass resolution has been achieved for biomolecules with MW > 12,000, and an accuracy of 1.4 ppm has been achieved for the average molecular weight of bovine insulin. PMID- 24214081 TI - 44th ASMS conference on mass Spectrometry. PMID- 24214084 TI - Toxic metals status in kidneys and gallstones of workers in a steel plant environment. AB - Samples of kidney stones and gallstones obtained from patients who were workers at a steel plant, or residents of the steel plant township area and those unrelated to the steel plant and steel plant township area were analysed for the presence of toxic metals (Zn, Cr, Ni, Co, Cu, Pb, Hg, Cd and Mn) by atomic absorption spectrophotometry. Other constituents (moisture, organic matter, oxalate, phosphate, fluoride and calcium) were also determined in each sample. In most of the samples the highest occurrence of toxic metals was found in the samples obtained from workers of the steel plant who were also residents of the steel plant township area. In samples obtained from patients who were non-workers of the plant but residents of the steel plant township area, the concentrations of the toxic metals were smaller, but higher than in those cases who were unrelated to the steel plant environment. PMID- 24214085 TI - The role of sample surveys for monitoring the condition of the nation's lakes. AB - In order to meet a growing need to determine the condition of the nation's ecosystems and how their condition is changing, the U.S. Environmental Protection Agency (EPA) developed EMAP, the Environmental Monitoring and Assessment Program. A common survey design serves as the foundation on which to base monitoring of status and trends among diverse ecosystem types. In this paper, we describe the need for a statistically based survey design, briefly summarize the basic EMAP design, describe how that design is tailored for the selection of a probability sample of lakes on which to make measurements of lake condition, and illustrate the process for selecting a sample of lakes in the northeastern United States. Finally, we illustrate how measurements taken on the sample of lakes can be summarized, with known uncertainty, to describe the condition of a population of lakes. PMID- 24214086 TI - A review of techniques for parameter sensitivity analysis of environmental models. AB - Mathematical models are utilized to approximate various highly complex engineering, physical, environmental, social, and economic phenomena. Model parameters exerting the most influence on model results are identified through a 'sensitivity analysis'. A comprehensive review is presented of more than a dozen sensitivity analysis methods. This review is intended for those not intimately familiar with statistics or the techniques utilized for sensitivity analysis of computer models. The most fundamental of sensitivity techniques utilizes partial differentiation whereas the simplest approach requires varying parameter values one-at-a-time. Correlation analysis is used to determine relationships between independent and dependent variables. Regression analysis provides the most comprehensive sensitivity measure and is commonly utilized to build response surfaces that approximate complex models. PMID- 24214087 TI - Health hazard assessment in an industrial town with the help of GRAM-GIS. AB - Unplanned industrialization and urbanization are causing health hazard mainly in developing countries. It is essential to assess the magnitude of future hazard in an industrial town. The geographical information system is a special type of tool evolved to analyse geographic data for efficient planning. In India large-scale industrialization started after independence. New industrial towns have been established and Durgapur in West Bengal is one of them. In this study an indigenously developed GIS package GRAM has been used to assess air quality in Durgapur town. Using GIS, interpolated maps have been prepared showing the distribution of five pollutants, i.e. carbon monoxide, total oxidant, nitrogen oxide, sulfur-dioxide and suspended particulate matter. The maps have been used to find the pollutant standard index of the area. The final map shows that the PSI index is high and ranges between the 'unhealthy' to 'very unhealthy' category. This map has been combined with a present landuse pattern. There are three pockets of extremely poor air quality zones which generally match with industrial units. Areas around these units are the potential zones of health hazard. Large numbers of patients admitted in hospitals here suffer from obstructive diseases. Most of them belong to the working age group. This may indicate that the main work force is exposed to the health hazard due to industrial pollution. PMID- 24214088 TI - A model with mass transport limitations for pump and treat remediation of soils polluted with NAPL. AB - A model is presented for the description of the pump and treat (or flushing) remediation of the saturated zone with non-aqueous phase liquid (NAPL) present as droplets. Sensitivity analysis shows that the most important variables are the NAPL droplet size and the distance through which the dissolved organic compound must diffuse to reach the advecting aqueous phase. The time needed to achieve complete remediation for different initial contaminant concentrations in soil depends more on the NAPL droplet radius and the size of the stagnant boundary layer than on the initial contaminant mass itself. Location of wells and flux rates are of little significance over the time needed for completion as long as all the water that flows through the contaminated region is captured in the recovery well. PMID- 24214089 TI - Reassessment of the role of the central cholinergic system. AB - The central cholinergic system is believed to be involved in the control of many physiological functions and is an important pharmacological target for numerous neurological pathologies. Here, we summarize our recent observations regarding this topic that we obtained by studying genetically modified mice devoid of particular cholinesterase molecular forms. Our results, collected from mice with deficits of functional cholinesterases in the brain, suggest that the increase in the level of acetylcholine (ACh) has an impact on cognition only in the situation when extracellular ACh is low. Furthermore, we confirmed the central control of movement coordination, which could be of importance for the management of motor problems in patients with Parkinson's disease. At last, we provide clear evidence that while the hypothermic effect of the muscarinic agonist oxotremorine is based on a central mechanism, in contrast, the acetylcholinesterase inhibitor donepezil decreases body temperature by its action in the periphery. PMID- 24214092 TI - A humpty dumpty language? PMID- 24214090 TI - Early referral for esophageal pH monitoring is more cost-effective than prolonged empiric trials of proton-pump inhibitors for suspected gastroesophageal reflux disease. AB - INTRODUCTION: The most cost-effective diagnostic algorithm for gastroesophageal reflux disease (GERD) remains controversial. We hypothesized that prompt referral for esophageal pH monitoring is more cost-effective than prolonged empiric courses of proton-pump inhibitors (PPIs). DISCUSSION: A cost model was created based on a cohort of 100 patients with possible GERD who underwent pH monitoring. The additional costs incurred from pH monitoring were compared to the potential savings from avoiding unnecessary PPI usage in patients with a negative pH study. The costs of PPI therapy reach equivalence with pH monitoring after 6.4 to 23.7 weeks, depending on the PPI regimen. A total of 21,411 weeks of PPIs were prescribed beyond the recommended 8-week trial, of which 32 % were for patients who had a negative 24-h pH monitoring study. If the sensitivity of pH monitoring was 96 %, early referral for pH monitoring would have saved between $1,197 and $6,303 per patient over 10 years. This strategy remains cost-effective as long as the sensitivity of pH monitoring is above 35 %. Prompt referral for pH monitoring after a brief empiric PPI trial is a more cost-effective strategy than prolonged empiric PPI trials for patients with both esophageal and extraesophageal GERD symptoms. PMID- 24214091 TI - Human Noxin is an anti-apoptotic protein in response to DNA damage of A549 non small cell lung carcinoma. AB - Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA-binding C-domain in RPA1, which mediates DNA metabolic processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen-activated protein kinase (MAPK)/p53 in non-small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA-damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage-induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti-tumor efficacy. Thus, hNoxin is a DNA damage-induced anti-apoptotic protein and potential therapeutic target in cancer. PMID- 24214093 TI - Hydrogeochemical studies for Al, F and Fe in waters supplying haemodialysis units in the Trent region, U.K. AB - Geographical and seasonal variations in the concentrations of Al, F and Fe in tap water supplying home haemodialysis units within the administrative area of the Trent Regional Health Authority, have been examined. Aluminium and fluoride were considered for their implications in bone disorders and iron for its competitive binding with aluminium to transferrin in serum. Four different water treatment systems are currently used and the extractive performance of these have been assessed. In general, the current Department of Health and Social Security's (DHSS) guidelines for aluminium in water used to prepare dialysate are met (30 MUg/l), but the proposed European Economic Community's (EEC) levels of 10 MUg/l, are not. The removal of fluoride and iron from water by the different treatments was comparable to the removal of aluminium. A comparison between old and new equipment highlights the importance of regular monitoring and maintenance. PMID- 24214094 TI - The critical level of cadmium in renal cortex: the concept and its limitations. AB - Because renal cortex is a primary target organ of Cd the seriousness of human exposure is commonly assessed in terms of the extent to which it permits renal cortical Cd concentrations to approach a critical value. The critical value has been defined in terms of PCC-10, the population critical concentration at which 10% of exposed individuals may be expected to show abnormal renal function. In chronically exposed human populations, PCC-10 appears to lie in the range of 180 to 220 MUg Cd/gram fresh weight of cortex. However, Cd accumulated in the kidney under these conditions is distributed between more than one compartment, in all likelihood differing greatly in their toxicological characteristics. For instance, a major fraction of this Cd is bound to metallothionein, and may as such be relatively inert. Compartmentation of tissue Cd, in turn, is strongly influenced by the nature of exposure, and the PCC-10 value of 200 MUg/g may therefore have limited general significance. The problem of risk assessment is further complicated by the high variability of Cd absorption. Nevertheless, human renal Cd levels commonly reach values as high as 1/3 to 1/6 of the chronic PCC 10, and further increases in Cd intake should therefore be avoided. PMID- 24214095 TI - Effects of sulphur deposition on trace metal solubility in soils. AB - Concentrations of Fe, Mn, Zn, Pb, Cu and Cd in soil solutions taken in the vicinity of a sulphur mine range from 354 to 9080 MUM L(-1), and exceeded the concentrations measured in solutions from light acid arable soils. The content of each metal was a negative function of either the solution pH or of Ca concentration.Reclamation of S-contaminated soil by an application of 2000 tonnes of limestone per hectare did not significantly affect the solubility of trace metals, whereas equilibration of soil samples with CaCO3 in the laboratory decreased solubility of metals, especially in the soil under moist conditions.Sulphur deposition may modify the natural cycling of metals in soils. PMID- 24214096 TI - Experimental assessment of wind erosion after soil stabilization treatments at Eneabba, Western Australia. AB - Wind tunnel experiments on rehabilitation surfaces at Eneabba, Western Australia evaluated the techniques used by Associated Minerals Consolidated Ltd. (AMC) and Allied Eneabba Ltd. (AEL) to stabilize regions being revegetated following heavy mineral sand mining.Newly landscaped areas proved to be the most erodible, beginning to erode at 9 m sec(-1) and producing a soil flux of 10 kg m(-1) min( 1) at 18 m sec(-1) wind speeds. Sandier, more organically-rich, surfaces in the rehabilitation areas were somewhat less erodible with losses of only 2 kg m(-1) min(-1) at wind speeds of 18 m sec(-1).The mining companies use various nurse crops and top dressing mulch for surface stabilization. Rows of oats, sparse plantings of the grass cultivar "SUDAX" (Dekalb ST6) supplied by Westfarmers Ltd. and applications of Terolas, a cold, bituminous surface binding material supplied by Shell Co. of Australia Ltd., all proved successful in reducing wind erosion in this semi-arid region where more than 25% of summer days experience winds greater than 8 m sec(-1). PMID- 24214097 TI - Nitrate content of vegetables commercially grown on land subject to inorganic or organic fertiliser. AB - A relatively quick and simple spectrophotometric method of measuring nitrate concentrations in vegetables has been used incorporating a Cu-Zn couple to provide a nitrate-free reference sample. This technique has been used in a preliminary study of the nitrate content of carrots and cabbages commercially grown on soils treated with either inorganic or organic fertiliser and available through normal retail outlets. Although it cannot be concluded that the nitrate levels in the organically fertilised vegetables were lower than those grown using conventional inorganic fertiliser, it can be concluded that the precise conditions of cultivation and soil do affect the nitrate levels in carrots and cabbages grown commercially. PMID- 24214098 TI - The society for environmental geochemistry and health conferences supported by the society in 1987. PMID- 24214099 TI - Spatiotemporal expression pattern of Myt/NZF family zinc finger transcription factors during mouse nervous system development. AB - BACKGROUND: Three members of the Myt/NZF family of transcription factors are involved in many processes of vertebrate development. Several studies have reported that Myt1/NZF-2 has a regulatory function in the development of cultured oligodendrocyte progenitors or in neuronal differentiation during Xenopus primary neurogenesis. However, little is known about the proper function of Myt/NZF family proteins during mammalian nervous system development. To assess the possible function of Myt/NZF transcription factors in mammalian neuronal differentiation, we determined the comparative spatial and temporal expression patterns of all three types of Myt/NZF family genes in the embryonic mouse nervous system using quantitative reverse transcriptase polymerase chain reaction and in situ hybridization. RESULTS: All three Myt/NZF family genes were extensively expressed in developing mouse nervous tissues, and their expression was transient. NZF-1 was expressed later in post-mitotic neurons. NZF-2 was initially expressed in neuronal cells a little earlier than NZF-3. NZF-3 was initially expressed in neuronal cells, just after proliferation was complete. CONCLUSION: These expression patterns suggest that the expression of NZF family genes is spatially and temporally regulated, and each Myt/NZF family gene may have a regulatory function in a specific phase during neuronal differentiation. PMID- 24214100 TI - Pharmacotherapy for trichotillomania. AB - BACKGROUND: Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated. OBJECTIVES: To assess the effects of medication for trichotillomania in adults compared with placebo or other active agents. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (to 31 July 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). Two review authors identified relevant trials by assessing the abstracts of all possible studies. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of a medication versus placebo or active agent for TTM in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the data extraction and 'Risk of bias' assessments, and disagreements were resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of trichotillomania symptoms on a continuous measure of trichotillomania symptom severity, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CIs). MAIN RESULTS: We identified eight studies with a total of 204 participants and a mean sample size of 25. All trials were single-centre trials, and participants seen on an outpatient basis. Seven studies compared medication and placebo (n = 184); one study compared medication and another active agent (n = 13). Duration of the studies was six to twelve weeks. Meta-analysis was not undertaken because of the methodological heterogeneity of the trials. The studies did not employ intention-to-treat analyses and were at a high risk of attrition bias. Adverse events were not well-documented in the studies.None of the three studies of selective serotonin reuptake inhibitors (SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment. AUTHORS' CONCLUSIONS: No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes. PMID- 24214101 TI - Demand for prescription drugs under non-linear pricing in Medicare Part D. AB - We estimate the price elasticity of prescription drug use in Medicare Part D, which features a non-linear price schedule due to a coverage gap. We analyze patterns of drug utilization prior to the coverage gap, where the "effective price" is higher than the actual copayment for drugs because consumers anticipate that more spending will make them more likely to reach the gap. We find that enrollees' total pre-gap drug spending is sensitive to their effective prices: the estimated price elasticity of drug spending ranges between [Formula: see text]0.14 and [Formula: see text]0.36. This finding suggests that filling in the coverage gap, as mandated by the health care reform legislation passed in 2010, will influence drug utilization prior to the gap. A simulation analysis indicates that closing the gap could increase Part D spending by a larger amount than projected, with additional pre-gap costs among those who do not hit the gap. PMID- 24214102 TI - Does an increase in serum creatinine always reflect renal injury? The case of Stribild(r) AB - Single tablet, once-daily HIV treatment regimens offer patient convenience, the potential for increased adherence, and fewer patient-related dosing errors[1] . Stribild(r) (manufactured and marketed by Gilead Sciences; referred to as "applicant" in this report), a 4-drug fixed-dose combination (FDC) tablet, is approved for the treatment of HIV-1 infection in treatment-naive adult patients. Stribild(r) contains elvitegravir (an integrase strand transfer inhibitor), cobicistat (an inhibitor of cytochrome P450 enzymes), and the nucleoside/nucleotide reverse transcriptase inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). PMID- 24214103 TI - Characterizing the role of PCDH9 in the regulation of glioma cell apoptosis and invasion. AB - PCDH9, a member of the protocadherin superfamily, is frequently lost in many different cancer types. This study aimed to detect PCDH9 expression in glioma tissues. This study also assessed the effects of PCDH9 expression in two different glioma cell lines. This was accomplished by manipulating PCDH9 expression in these glioma cell lines. The data showed that the expression of PCDH9 mRNA and protein was significantly decreased in gliomas compared to normal brain tissues. Lentivirus carrying PCDH9 cDNA restored PCDH9 expression in the U87 and U251 glioma cell lines. PCDH9 restoration in these cell lines reduced tumor cell viability, induced apoptosis, and caused G0/G1 cell cycle arrest. PCDH9 expression also suppressed the colony formation ability and invasion capacity of U87 and U251 cells. Molecularly, the restoration of PCDH9 expression upregulated Bax protein expression, but downregulated Bcl-2 and cyclin D1 expression. These data from the current study suggest that the loss of PCDH9 expression could contribute to glioma development and/or progression. Further studies will evaluate PCDH9 expression as a biomarker for the early detection of gliomas and as a prognostic indicator for this cancer type. PMID- 24214104 TI - Effect of cocaine on ion channels and glutamatergic EPSCs in noradrenergic locus coeruleus neurons. AB - The locus coeruleus (LC) is an important brainstem area involved in cocaine addiction. However, evidence to elucidate how cocaine modulates the activity of LC neurons remains incomplete. Here, we performed whole recordings in brain slices to evaluate the effects of cocaine on the sodium (Na(+)), potassium (K(+)), calcium (Ca(2+)) channels, and glutamatergic synaptic transmission in the locus coeruleus neurons. Local application of cocaine significantly and reversibly reduced the spontaneous firing rate but did not affect action potential amplitude, rising time, decay time, or half width of noradrenergic locus coeruleus neurons. Moreover, cocaine attenuated the sodium current but did not affect potassium and calcium currents. The N-methyl-D-aspartate receptor mediated excitatory postsynaptic currents were reduced by neuropeptide galanin but not cocaine. All those data demonstrate that cocaine has inhibitory effect on the spontaneous activities and sodium current in locus coeruleus neurons. Therefore, neuromodulation of sodium channel in locus coeruleus neurons may play an important role in drug addiction. PMID- 24214105 TI - Flexible and elastic scaffolds for cartilage tissue engineering prepared by stereolithography using poly(trimethylene carbonate)-based resins. AB - The aim of this study is to investigate the applicability of flexible and elastic poly(trimethylene carbonate) (PTMC) structures prepared by stereolithography as scaffolds for cartilage tissue engineering. A three-armed methacrylated PTMC macromer with a molecular weight of 3100 g mol(-1) is used to build designed scaffolds with a pore diameter of 350 +/- 12 MUm and a porosity of 54.0 +/- 2.2%. Upon seeding of bovine chondrocytes in the scaffolds, the cells adhere and spread on the PTMC surface. After culturing for 6 weeks, also cells with a round morphology are present, indicative of the differentiated chondrocyte phenotype. Sulphated glycosaminoglycans and fibrillar collagens are deposited by the cells. During culturing for 6 weeks, the compression moduli of the constructs increases 50% to approximately 100 kPa. PMID- 24214107 TI - Introductory paragraph--Volume 27, Issue 12. PMID- 24214108 TI - Physiotherapy interventions aimed at the recovery of arm function and of gait ability in stroke patients can hardly be viewed as independent of each other. PMID- 24214109 TI - Meta-analysis amplifies the conclusions of a systematic review. Comment on the systematic review of Vancampfort et al. 'Progressive muscle relaxation in persons with schizophrenia: a systematic review of randomized controlled trials'. PMID- 24214110 TI - Platelet-rich plasma in rotator cuff lesions. PMID- 24214111 TI - Healing of partial thickness tears? PMID- 24214113 TI - Specific and nonspecific dimer formation in the electrospray ionization mass spectrometry of oligonucleotides. AB - Specific and nonspecific noncovalent dimer ions of oligonucleotides (ODNs) were observed when mixtures of complementary or noncomplementary strands were analyzed via negative ion electrospray ionization mass spectrometry. Dimer formation was concentration dependent and nearly always occurred when the concentration of ODN exceeded 100 uM. Dimers were observed even for short-length ODNs for which the melting temperature (T m) was well below the experimental temperature and which, therefore, would not be expected to form stable solution duplexes. The abundance of the heterodimer ions seems to correlate with the number of expected hydrogen bonds from Watson-Crick base pairing. As the energy of the incoming ion beam (orifice potential) was increased, the absolute and relative abundance of the dimer ions unexpectedly increased. PMID- 24214114 TI - Static secondary ionization mass spectrometry analysis of tributyl phosphate on mineral surfaces: Effect of Fe(II). AB - The static secondary ionization mass spectrometry (SIMS) spectrum of tri-n-butyl phosphate (TBP) on a variety of basalt and quartz samples is affected by the chemical composition of the mineral surface. When TBP is adsorbed on Fe(II) bearing surfaces, the compound undergoes concomitant H(-) abstraction and reduction, followed by the elimination of two C4H8 molecules to form an ion at m/z 137(+). When TBP is adsorbed to quartz or other nonreducing surfaces, it merely undergoes protonation and elimination of three C4H8 molecules to form H4PO 4 (+) . When TBP is adsorbed to Fe(III)-bearing surfaces, it undergoes H(-) abstraction and elimination of two C4H8 molecules, to form an ion at m/z 153(+). These conclusions are supported by model studies that employed FeO, Fe203, TBP, and tributyl phosphite. The results show that the SIMS spectrum is very sensitive to the mode of TBP adsorption on the mineral surface. PMID- 24214115 TI - Interface for a four-sector mass spectrometer with a dual-purpose collision cell: High transmission at low to intermediate energies. AB - A new interface system that consists of an ion decelerator, a floating collision cell-chemical ionization ion source, and an ion extractor was designed and installed in the third field-free region of a four-sector tandem mass spectrometer. Important features include the use of cylindrical deceleration lenses and an extraction lens assembly. This new design was found to provide enhancement of ion transmission at low to intermediate ion kinetic energies (3 eV to 1 keV) compared with the standard collision cell design. Collision-induced dissociation experiments from 3 eV to 10 keV and ion-molecule reactions of mass selected ions can be performed conveniently. A second, grounded, collision cell is located after the extraction lenses, which allows MS(4) experiments to be carried out via the normal linked (B/E) scan function in MS2. Incorporation of chemical ionization capability into the electrically isolated collision cell makes it possible to carry out neutralization chemical-reionization mass spectrometry. PMID- 24214112 TI - Should there be sex-specific criteria for the diagnosis and treatment of heart failure? AB - All-cause mortality from cardiovascular disease is declining in the USA. However, there remains a significant difference in risk factors for disease and in mortality between men and women. For example, prevalence and outcomes for heart failure with preserved ejection fraction differ between men and women. The reasons for these differences are multifactorial, but reflect, in part, an incomplete understanding of sex differences in the etiology of cardiovascular diseases and a failure to account for sex differences in pre-clinical studies including those designed to develop new diagnostic and treatment modalities. This review focuses on the underlying physiology of these sex differences and provides evidence that inclusion of female animals in pre-clinical studies of heart failure and in development of imaging modalities to assess cardiac function might provide new information from which one could develop sex-specific diagnostic criteria and approaches to treatment. PMID- 24214116 TI - Chemical modification of fluorinated self-assembled monolayer surfaces by low energy reactive ion bombardment. AB - Reactive collisions of low energy (<100-eV) mass-selected ions are used to chemically modify fluorinated self-assembled monolayer surfaces comprised of alkanethiolate chains CF3(CF2)11(CH2)2S- bound to Au. Typical experiments were done by using 1-nA/cm(2) beams and submonolayer doses of reactant ions. Characterization of the modified surface was achieved by in situ chemical sputtering (60-eV Xe(+.)) and by independent high mass resolution time-of-flight secondary ionization mass spectrometry (TOF-SIMS) (15-25-keV, Ga(+)) experiments. Treatment with Si(35)C1 4 (+.) produced a surface from which Xe(+) sputtering liberated CF2 (35)C1(+) ions, which suggested Cl-for-F halogen exchange at the surface. Isotopic labeling studies that used Si(35)Cl2 (37)Cl 2 (+.) ; and experiments with bromine-containing and iodine-containing projectiles, confirmed this reaction. High mass resolution TOF-SIMS spectra, as well as high spatial resolution images, provided further evidence as to the existence of halogen exchanged species at the bombarded surface. Analogous Cl-for-F halogen substitution was observed in a model gas-phase reaction. The ion-surface reaction is suggested to proceed through an intermediate fluoronium ion in which the projectile is bonded to the target molecule. The most significant conclusion of the study is that selective chemical modification of monolayer surfaces can be achieved by using reactive ion beams, which lead to new covalent bonds at the surface and in the scattered ions. PMID- 24214117 TI - Electron-impact-induced 3,3-sigmatropic rearrangement and cyclization in phenyl allenylmethyl ethers. AB - A 3,3-sigmatropic rearrangement in the M(+.) of phenyl allenylmethyl ether is proposed for the observed losses of CO, C2H4, and CH3. Direct cyclization in the M(+.) also leads to the [M-CH3] ion. The presence of sulfur as the heteroatom in phenyl allenylmethyl sulfide does not significantly influence the occurrence of Claisen rearrangement. Ortho interaction of the nitro group with the allenyl double bond in the side chain leads to characteristic fragment ions in 2 nitrophenyl allenylmethyl ether. Linked scans, high-resolution mass spectrometry, collision-activated dissociation-B/E linked-scan spectra, and D-labeling have been employed to support the proposed mechanisms and ion structures. PMID- 24214118 TI - Fragmentation of the metastable molecular ion of methyl lactate: The formation of oxygen-protonated methanol [CH3OH 2] (+) involving double hydrogen atom transfers. AB - The spontaneous unimolecular dissociation reaction of methyl lactate (1) ionized by electron impact was investigated by a combination of mass-analyzed ion kinetic energy spectrometry and deuterium labeling. The metastable ions 1(+.) decompose in a variety of ways: four fragment peaks are observed at m/z 89, 76, 61, and 45, which correspond to the losses of CH3, CO, CH3CO, and COOCH3, respectively. Double hydrogen atom transfer occurs in the third reaction.The source-generated m/z 61 ions decompose into oxygen-protonated methanols at m/z 33 ([CH3OH 2 (+) ]) by the loss of CO with double hydrogen atom migration. Both hydroxyl and methyne hydrogen atoms in 1 (+.) are present in the resultant protonated methanols. PMID- 24214119 TI - Correlation of stereoselectivity and ion response in electrospray mass spectrometry. electrospray ionization-mass spectrometry as a tool to predict chemical behavior? AB - Several alkali cation complexes of chiral alkoxymethyl-substituted acylsilanes, prepared in situ by the admixture of alkali iodides to acylsilane sample solutions, were investigated by electrospray ionization-mass spectrometry. Competition experiments suggest that the relative complex stabilities of such species in acetonitrile solution follow the order [Formula: see text], which is different from the order of the relative stabilities of the complexes in the gas phase ([Formula: see text]) as qualitatively determined by a tandem mass spectrometry-type experiment. Additionally, a rough correlation of relative ion responses in the mass spectrometry with relative stereoselectivities-derived from chelate-controlled reactions performed with the respective silanes-was found. The latter observation suggests that the electrospray ionization-mass spectrometry technique is a potentially useful method to predict chemical behavior, and it demands little experimental effort. PMID- 24214120 TI - Influence of the length and position of the collision cell on the resolving power attainable from collisionally activated processes in sector instruments. AB - The energy resolution in a high resolution tandem mass spectrometer was investigated in terms of the length and position of the central collision cell. Both these parameters have to be chosen carefully to eliminate collisional broadening phenomena that can severely limit the energy resolution in such instruments. A theory that describes collisional broadening, to first order, has been derived that accounts for the observed phenomena. It was found experimentally that collisional broadening can be reduced to less than 0.001 eV per kiloelectronvolt collision energy. Experimental data confirmed that only the size of the resolving slits and thermal broadening, due to the target gas, limited the ultimate energy resolution available. PMID- 24214121 TI - Complete large-molecule high-resolution mass spectra from 50-femtomole microvolume injection. AB - For electrospray ionization in Fourier-transform mass spectrometry, direct injection of 5*10(-14) mol (0.5 uL of 100 nM from a microvolume sample valve) of ubiquitin (8565 Da) into the flowing solvent stream yields a spectrum with 85:1 signal-to-noise ratio, 2-ppm mass accuracy, and isotopic resolution. Gated trapping for 100 us from a 0.15-uL/min injection of 20-uM ubiquitin consumes 5*10(-18) mol, which produces a spectrum with 23:1 signal-to-noise ratio and tau;3*10(5) resolving power. PMID- 24214124 TI - The maize d2003, a novel allele of VP8, is required for maize internode elongation. AB - The d2003 is a natural dwarf mutant from maize inbred line K36 and has less than one-third of K36 plant height with severely shortened internodes. In this study, we reported the cloning of d2003 gene using positional cloning. The results showed that there was a single-base insertion in the coding region of Viviparous8 (VP8) in d2003 mutant, which resulted in a premature stop codon. Further genetic allelism tests confirmed that d2003 mutation is a novel allele of VP8. VP8 is mainly expressed in the stem apex, young leaves, and developing vascular tissues, and its expression levels in nodes are significantly higher than that in internodes at 12-leaf stage. Subcellular localization demonstrated that the VP8 protein is localized to the endoplasmic reticulum and the N-terminal 26 amino acids (aa) of VP8 protein are essential to its localization in ER. Further transgenic experiments showed that lack of the 26 aa leads to loss of VP8 function in Arabidopsis amp1 phenotype rescue. These results strongly suggested that the N-terminal 26 aa is critical for VP8 protein localization, and the correct protein localization of VP8 in ER is necessary for its function. PMID- 24214125 TI - Controlled synthesis of multi-arm star polyether-polycarbonate polyols based on propylene oxide and CO2. AB - Multi-arm star copolymers based on a hyperbranched poly(propylene oxide) polyether-polyol (hbPPO) as a core and poly(propylene carbonate) (PPC) arms are synthesized in two steps from propylene oxide (PO), a small amount of glycidol and CO2 . The PPC arms are prepared via carbon dioxide (CO2 )/PO copolymerization, using hbPPO as a multifunctional macroinitiator and the (R,R) (salcy)CoOBzF5 catalyst. Star copolymers with 14 and 28 PPC arms, respectively, and controlled molecular weights in the range of 2700-8800 g mol(-1) are prepared (Mw /Mn = 1.23-1.61). Thermal analysis reveals lowered glass transition temperatures in the range of -8 to 10 degrees C for the PPC star polymers compared with linear PPC, which is due to the influence of the flexible polyether core. Successful conversion of the terminal hydroxyl groups with phenylisocyanate demonstrates the potential of the polycarbonate polyols for polyurethane synthesis. PMID- 24214126 TI - Reactive haemophagocytic syndrome in a patient with adult-onset Still's disease: beta-lactams as trigger? PMID- 24214127 TI - Incidence of herpes zoster in patients with altered immune function. AB - PURPOSE: To estimate the incidence of herpes zoster (HZ) and rates of post-zoster pain in both the total study population and separately in patients with selected conditions/treatments associated with altered immune function. METHODS: The health administrative claims databases for commercially insured, Medicare, and Medicaid populations, together accounting for approximately 51 million insured individuals, were analyzed between 2005 and 2009 in a retrospective cohort study. Incidence of HZ episodes per 1,000 person-years (PY) was estimated in all study populations as well as within nine potentially immune-altering conditions. Among patients with HZ, the 6-month rate of persistent post-zoster pain was estimated. RESULTS: Analysis of 90.2 million PY at risk revealed that the incidence of HZ in the total study population was 4.82/1,000 PY. The incidence of HZ was highest among patients with bone marrow or stem cell transplant (43.03 %) followed by solid organ transplant, human immunodeficiency virus infection, and systemic lupus erythematosus [95 % confidence interval (CI) 15.19-17.41 %]. HZ incidence rates were higher among persons on immunosuppressants/chemotherapy than among non users. In the total study population, HZ incidence increased with age (18-49 years: 3.37/1,000 PY; 65+ years: 8.43/1,000 PY; P < 0.01) and female gender (incidence ratio vs. male 1.39, 95 % CI 1.38-1.40 %). The 6-month rate of persistent post-zoster pain was 4.29 % (95 % CI 4.22-4.36 %), which was higher in patients with the selected conditions. CONCLUSIONS: Despite providing a relatively small fraction of overall HZ cases, persons with immune function altering conditions make a large contribution to the societal healthcare burden because they have a higher risk of developing HZ and persistent post-zoster pain. These risk factors should be considered in HZ prevention efforts. PMID- 24214129 TI - Commentary: a return to origins. PMID- 24214128 TI - Ribonucleotide reductase M2B inhibits cell migration and spreading by early growth response protein 1-mediated phosphatase and tensin homolog/Akt1 pathway in hepatocellular carcinoma. AB - Ribonucleotide reductase (RR)M2B is an enzyme belonging to the ribonucleotide reductase enzyme family, which is essential for DNA synthesis and repair. RRM2B plays an important role in tumor progression and metastasis; however, little is known about the expression and underlying molecular mechanisms of RRM2B in hepatocellular carcinoma (HCC). In the present study, we report that down regulation of RRM2B in HCC is negatively associated with intrahepatic metastasis, regardless of p53 status. Moreover, the ectopic overexpression of RRM2B decreased HCC cell migration and invasion in vitro, whereas silencing RRM2B expression resulted in increased migration and invasion in vitro and intrahepatic and lung metastasis in vivo. Additionally, knockdown of RRM2B by short hairpin RNA (shRNA) in HCC cells was associated with epithelial-mesenchymal transition (EMT), including the down-regulation of E-cadherin, and the concomitant up-regulation of N-cadherin and slug. A further experiment showed that RRM2B inhibited cell migration and spreading through regulation of the early growth response protein 1 (Egr-1)/phosphatase and tensin homolog (PTEN)/Akt1 pathway. Consistently, we also detected a significant correlation between RRM2B and E-cadherin protein expression in HCC tissues. Furthermore, Egr-1 also directly bound to the RRM2B promoter and repressed RRM2B transcription, thereby establishing a negative regulatory feedback loop. CONCLUSION: These findings indicate that RRM2B suppresses cell migration and spreading by way of modulation of the Egr 1/PTEN/Akt1 pathway. PMID- 24214130 TI - Childhood cancer in Africa. AB - The majority of children with cancer live in low- and middle-income countries (LMICs) with little or no access to cancer treatment. The purpose of the paper is to describe the current status of childhood cancer treatment in Africa, as documented in publications, dedicated websites and information collected through surveys. Successful twinning programmes, like those in Malawi and Cameroon, as well as the collaborative clinical trial approach of the Franco-African Childhood Cancer Group (GFAOP), provide good models for childhood cancer treatment. The overview will hopefully influence health-care policies to facilitate access to cancer care for all children in Africa. PMID- 24214131 TI - Photoswitching of ortho-substituted azonium ions by red light in whole blood. PMID- 24214132 TI - Heavy metals in freshwater snails of Kuala Klawang's rice field, Negeri Sembilan, Malaysia. AB - A study of heavy metal contents in freshwater snails from rice fields have been made. The results indicate that the levels of heavy metals, Pb, Cu, Zn and Cd, are low and within the permissible limit of Malaysian Food Regulations. The results can serve as background data for further reference. PMID- 24214133 TI - Electrostatic precipitation in atmospheric aerosols. AB - The use of electrostatic force mechanisms can make a substantial contribution to control the pollution from air solids arising naturally, or from human development. In the present investigation we discuss the efficiency of a technique to precipitate the atmospheric aerosol of a size <5 um, by energizing metal mesh (Por=0.7) collectors (+, N, and -) using low D.C. voltage (0-30 V or 1.224*10(2) Vm(-1)). PMID- 24214134 TI - A shortened algal growth potential test. AB - The Algal Growth Potential Test has been an accepted standard test for measuring the bioavailability of nutrients in water bodies. A shortened seven day test has been developed, tested, and shown to have a strong correlation relationship with algal tests grown to maximum dry weight yields. The new test will save time in processing the samples and processing of test data. PMID- 24214135 TI - Factor analysis of trace-element data from tree-bark samples in The Netherlands. AB - Monte Carlo-assisted factor analysis has been applied to a data set of 20 trace element concentrations in tree-bark samples obtained from 123 locations in The Netherlands, with the aim to investigate the suitability of bark as a biomonitor for air pollution. A Monte Carlo approach was used to give more insight to the uncertainties and significance levels of the factor analysis results. Notwith standing a rather strong influence of soil material on the concentration levels, factor analysis enabled the identification of five significant pollution source types, all of which corresponded with source types found in an earlier biomonitoring study in The Netherlands using epiphytic lichens. A more detailed comparison with the lichen results showed a remarkable difference in lead concentrations between bark and lichen. It was concluded that bark can be successfully employed as a biomonitor for air pollution. The power of factor analysis to adequately determine the soil contribution may render extensive sample washing procedures superfluous. PMID- 24214136 TI - Risk assessment for salmon from water quality changes following timber harvesting. AB - Land use activities may affect surface water quantity and quality. Water quality changes (concentration increases) from land use activities that are above background but below the water quality standard or criteria have always been considered benign. Increased public interest and recent legislation and management regarding threatened, or endangered, salmon populations suggest that environmental influences on these populations need to be reevaluated.As one approach, we developed a risk assessment (toxicity and exposure) for salmon from water quality changes following timber harvesting. Toxicity relationships for nitrate-nitrogen (as an LC50) using chloride, suspended sediment, and exposure were developed from the literature and data from the Alsea Watershed Study in the Oregon Coast Range. These relationships were used to predict the probable risk to coho salmon (Oncorhynchus kisutch) to nitrate-nitrogen exposure.The control or reference catchment, Flynn Creek, had higher nitrate-nitrogen concentrations, but showed little likelihood of risk to salmon because of lower suspended sediment concentrations. The treated catchment, Needle Branch (harvested 27 years ago), had lower nitrate-nitrogen concentrations and was expected to have less risk to salmon. However, the risk assessment relationship exhibited sensitivity to suspended sediment concentrations. This smaller catchment had higher suspended sediment transport and thus a higher risk of nitrate-nitrogen exposure to salmon. The suspended sediment transport functions were based on post-treatment monitoring (1966-1973) and are not considered to represent the current situation. These findings are not meant to be categorical, but merely illustrative of this risk assessment application. PMID- 24214137 TI - Mercury accumulation in sediment and fish from rivers affected by alluvial gold mining in the Brazilian Madeira River basin, Amazon. AB - The degree and distribution of mercury (Hg) accumulation in sediment and fish from a tributary affected by alluvial small-scale gold mining in the Madeira River/Amazon is studied, in relation to a reference site. The results obtained so far agree well with previous studies and confirm that a tremendous contamination of main food web compartments occurs in these highly exposed, but vulnerable tropical waters. An essential part of the released metallic Hg may still exist as macroscopic liquid Hg drops in the sediment. Both global (0.4 mg/kg of Hg) and local (0.1 mg/kg of Hg) background sediment values as well as safety levels for fish (0.5 mg/kg of Hg) are considerably exceeded by a factor of up to 25, 100, and 4, respectively, and give rise to serious concern, not least with regard to the formation of the very toxic monomethyl-Hg. It is further discussed that atmospheric transport and deposition of Hg in water reservoirs built for hydroelectric power generation may act as critical pathways for longterm Hg accumulation, even in unexposed riverine systems. PMID- 24214138 TI - In-situ measurement of photosynthetic oxygen production in the water column. AB - A novel hardware device is described to determine photosynthetic and respiratory oxygen uptake and release, respectively, in organisms in their natural habitat even under the rough conditions of their marine environment. Both macroalgae and phytoplankton can be utilized and oxygen exchange can be determined in solar radiation. The chamber can be used at or above the water surface or can be lowered into the water column. The data of oxygen concentration, irradiance and temperature are constantly monitored by a laptop computer and stored in disk files. The experimental data measured in some macroalgae as well as in phytoplankton indicate that the irradiance window for positive net photosynthetic oxygen production is fairly limited under natural conditions; at too low irradiances respiration exceeds photosynthesis and at too high irradiances photosynthesis is shut down by photoinhibition, at least in species not adapted to unattenuated solar radiation. PMID- 24214139 TI - Use of cluster and principal component analyses to profile areas in California where ground water has been contaminated by pesticides. AB - An empirical approach to profiling areas of ground water contamination by pesticides was devised that did not rely upon determining the level of vulnerability between land areas and that did not assume any particular pathway for ground water contamination. Climatic and soil data were obtained for 1-square mile sections of land in California where pesticide residues had been found in well water samples and the detection was attributed to legal agricultural applications. These sections were designated as known contaminated (KC) sections. Climate and soil data were also obtained for sections which lacked either well sampling data or a positive pesticide detection. These sections were designated as candidate sections. Statistical procedures were used to cluster groups of KC sections first with respect to climate characteristics and then with respect to soil characteristics. Principal components analysis (PCA) was used to construct a statistical profile of soil variables for each cluster of KC sections. A method based on the PCA was developed to compare the similarity of soil profiles derived for each KC section cluster to individual candidate sections. Since the profiling scheme was based only on data from KC sections, candidate sections that did not match any KC cluster profile could only be considered dissimilar to contaminated sections, receiving a status of not-classified. This profiling method is flexible and it can be revised to incorporate updated well sampling information. PMID- 24214140 TI - Role of brimonidine in the treatment of clinically significant macular edema with ischemic changes in diabetic maculopathy. AB - To evaluate the role of brimonidine (BMD), an alpha-2 agonist, in the management of clinically significant macular edema (CSME) in diabetic maculopathy with ischemic changes. A prospective, randomized controlled trial including 30 eyes of 30 metabolically stable diabetic patients with CSME showing fundus fluorescein angiography documented ischemic changes. Group I included 17 eyes of patients who received topical BMD (0.2 %) twice daily for 6 months while Group II included 13 eyes of age-matched patients who were kept under observation and acted as controls. The mean change in logMAR visual acuity and any change in the grade of the foveal avascular zone (FAZ) size, outline, capillary non-perfusion, or capillary dilatation was noted in the two groups and compared at the end of 6 months. The FAZ area and radius was significantly less in the study group than the control group. However, no significant difference in FAZ capillary outline, FAZ capillary loss, FAZ capillary dilatation and overall grade of ischemia between the two groups was seen. There was improvement in visual acuity from baseline to 6 months but it was comparable between the two groups (p = 0.02). BMD may have a role in the treatment of ischemic macula in CSME since the FAZ area and radius were significantly less in the study group. However, a larger sample size and a longer follow-up are needed to further authenticate the results of this pilot study. PMID- 24214141 TI - The effect of CYP2C19 genotype on the time course of platelet aggregation inhibition after clopidogrel administration. AB - We evaluated the effect of CYP2C19 genotype over time on the antiplatelet response of clopidogrel in healthy subjects. Seventy subjects enrolled for a pharmacodynamic study and 22 subjects for a pharmacokinetic and pharmacodynamic study took 300 mg clopidogrel on the first day and 75 mg once daily for six consecutive days. The subjects with CYP2C19 poor metabolizers (PM, N = 22) and intermediate metabolizers (IM, N = 37) had significantly delayed time to inhibition of platelet aggregation (IPA) compared with CYP2C19 extensive metabolizers (EM, N = 33) (12 vs. 9 vs. 2 hours as median Tmax , P < .05) after a 300 mg of clopidogrel. During maintenance doses of clopidogrel, IPA values of only CYP2C19 PM subjects were gradually decreased from 30.0 +/- 21.9% on day 2 to 23.7 +/- 16.6% on day 8 (P > .05 for time effect; P < .05 for time and genotype interaction effect). CYP2C19 PM had decreased Cmax and AUC of thiol metabolite compared with CYP2C19 EM (0.42- and 0.37-fold on day 1, P < .01; 0.39- and 0.34 fold on day 7, P < .01, respectively). Delayed time to reach maximal IPA as well as decreased IPA may influence the increased risk of the acute cardiac events in CYP2C19 PM and IM. PMID- 24214142 TI - Inhibition of Niemann-Pick-type C1-like1 by ezetimibe activates autophagy in human hepatocytes and reduces mutant alpha1-antitrypsin Z deposition. AB - Autophagy can degrade aggregate-prone proteins, but excessive autophagy can have adverse effects. It would be beneficial if autophagy could be enhanced in a cell type-specific manner, but this has been difficult because the basic mechanism of autophagy is common. In the present study we found that inhibition of Niemann Pick-type C1-like 1 (NPC1L1) by ezetimibe activates autophagy only in hepatocytes and small intestinal epithelia, but not in other cells. Ezetimibe induced accumulation of free cholesterol in the late endosome/lysosome and increased partitioning of a Ragulator component, LAMTOR1, in rafts. The latter change led to down-regulation of mammalian target of rapamycin (mTOR)C1 activity by decreasing mTOR recruitment to the late endosome/lysosome and activated autophagy. A primary effect of ezetimibe was found to be a decrease of free cholesterol in the plasma membrane, because all the results caused by ezetimibe were suppressed by supplementation of cholesterol as a methyl-beta-cyclodextrin complex. By enhancing autophagy in human primary hepatocytes with ezetimibe, insoluble mutant alpha1-antitrypsin Z was reduced significantly. CONCLUSION: Inhibition of NPC1L1 by ezetimibe activates autophagy in human hepatocytes by modulating cholesterol homeostasis. Ezetimibe may be used to ameliorate liver degeneration in alpha1-antitrypsin deficiency. PMID- 24214143 TI - Air lead concentrations in Birmingham, England - a comparison between levels inside and outside inner-city homes. AB - Air lead concentrations were monitored for seven consecutive days at two locations inside and one location immediately outside 97 houses in inner-city Birmingham. Concentrations in the bedroom and playroom were similar to each other, but usually lower than those found outdoors. The mean internal air lead concentration was 0.26 MUg/m(3) (n=1206) and the mean external concentration, 0.43 MUg/m(3) (n=605). The mean of the individual internal:external ratios was 0.61 and similar to others cited in the literature. The study indicates that, in the absence of any major internal sources of lead, the mean external air lead concentration is a good predictor of the mean air internal air lead concentration. PMID- 24214144 TI - Soil compaction in topsoil replacement during mining reclamation. AB - Current U.S. mining regulations require revegetation in reclaiming surface mines. Excessive soil compaction can be an impediment to successful revegetation in poor soil conditions common to Eastern U.S. coal mine sites. A field study was performed to determine the bulk densities of soils that had been spread by either bulldozers or scrapers at a strip mine site. Moisture-density relationships for the soils were determined from the field samples. These were compared with samples compacted by the Standard Proctor compaction test. The results of the study indicate that the degree of compaction, could be lessened through proper soil handling procedures. PMID- 24214145 TI - Toxicity of root-applied sulphite in Zea mays. AB - Zea mays was grown in nutrient solution with different concentrations of sulphite and sulphate (0, 5, and 10 mM) at pH 5 or 7, with or without aeration, for five days. Sulphite injured the plants, especially at low pH. Lack of aeration increased the sulphite injury of the plants at the high pH. in the aerated solutions, sulphite concentrations approached zero after five hours, while the unaerated solutions still contained sulphite after four days. Very little sulphite was found in the plants. The results indicate that the toxicity to the plants of the different chemical species of the sulphite in the solution decreases in the following order: SO2 (aq) > HSO3 (-) > SO3 (2-). PMID- 24214146 TI - Modelling of leachates from dolomitic mine tailings. AB - The REDEQL.EPAK computer model was used to study speciation of Pb, Cd, Zn, and Ca in leachates from dolomitic Pb mine tailings. By allowing or disallowing precipitation of solids and equilibration of the modelled leachate with atmospheric C02, comparison of fresh and aged leachates was made. The effects of treatment of the tailings with phosphate containing fertilizer were studied through addition of P04 (3-) to the modelled solution. Equilibrium constants pertaining to metal ion-humic acid complexation were added to the thermodynamic data base of the model in order to study the effects of decaying plant material on tailings leachate.Initial leachate of the tailings is found to be supersaturated with Cd and Zn. Non-complexed ("free") Cd(2+) and Zn(2+) is predicted to comprise most of the soluble form of these metals in the leachate; Pb is predicted to be present largely as PbCO3 ion pair. Equilibration of the leachate with the atmosphere is predicted to lead to extensive precipitation of CdCO3 and ZnSiO3. Precipitation of Pb5(PO4)3Cl is predicted at high PO4 (3-) concentration and at low pH. Complexation by the humic acid is predicted to compete effectively with other ligands in the leachate for the metal ions. The results are compared with experimental findings. PMID- 24214147 TI - Detection of an ABCA1 variant associated with type 2 diabetes mellitus susceptibility for biochemistry and genetic laboratory courses. AB - We selected diabetes mellitus for this laboratory exercise to provide students with an explicit model for scientific research concerning the association between the R230C polymorphism and susceptibility to type 2 diabetes mellitus, which is highly prevalent in the Mexican population. We used a collaborative project-based learning to engage students to direct their own learning process. Students worked in small groups with the same learning goal to research, organize data, and present seminars to experimentally genotype the C230 variant and correctly interpret their results. At the conclusion of this laboratory exercise, the students were able to demonstrate a clear understanding of the relevant biological molecular principles to genotype the C230 variant, showed technical competency to carry out the experimental protocols with proficiency, and interpret their results using statistical analyses. The students discussed their understanding of the genetic technologies and the broader social and ethical implications of the research. A randomly selected team was trained to work as a "sentinel" to monitor their classmates and ensure the proper application of techniques. Moreover, the evaluation of this exercise is shared between the students and the instructors; the students evaluate their own work and the performance of their classmates. At the end of the course, the students complete a questionnaire to anonymously provide feedback and information regarding their perception of the learning outcomes. Overall, the student feedback was positive, indicating that the exercise was useful and that it would help to prepare the students for professional practice. PMID- 24214148 TI - "Because I am worth it": a theoretical framework and empirical review of a justification-based account of self-regulation failure. AB - Self-regulation failure is often explained as being overwhelmed by impulse. The present article proposes a novel pathway, presenting a theoretical framework and empirical review of a justification-based account of self-regulation failure. With justification we refer to making excuses for one's discrepant behavior, so that when experiencing a self-regulation dilemma between immediate impulses and long-term intentions, people resolve the conflict by developing and employing justifications that allow violations of the goal they endorse. Accordingly, rather than inhibiting motivations from the impulsive system, the reflective system can also facilitate them, leading to self-regulation failure. We bring together empirical evidence from various domains demonstrating that justifications can instigate self-regulation failure and rule out alternative accounts. Having established that justification processes contribute to self regulation failure, we then propose several mechanisms that may fuel the effect. Finally, routes for future research and the conceptual and practical implications of these novel insights for self-regulation are discussed. PMID- 24214149 TI - Improving the dependability of research in personality and social psychology: recommendations for research and educational practice. AB - In this article, the Society for Personality and Social Psychology (SPSP) Task Force on Publication and Research Practices offers a brief statistical primer and recommendations for improving the dependability of research. Recommendations for research practice include (a) describing and addressing the choice of N (sample size) and consequent issues of statistical power, (b) reporting effect sizes and 95% confidence intervals (CIs), (c) avoiding "questionable research practices" that can inflate the probability of Type I error, (d) making available research materials necessary to replicate reported results, (e) adhering to SPSP's data sharing policy, (f) encouraging publication of high-quality replication studies, and (g) maintaining flexibility and openness to alternative standards and methods. Recommendations for educational practice include (a) encouraging a culture of "getting it right," (b) teaching and encouraging transparency of data reporting, (c) improving methodological instruction, and (d) modeling sound science and supporting junior researchers who seek to "get it right." PMID- 24214150 TI - Curious case of missing (A) in coeliac disease with type 1 diabetes mellitus. AB - Coeliac screening in type 1 diabetes mellitus (T1DM) is universally recommended, but not all authorities recommend serum IgA estimation before using an IgA-based test. We report a case of T1DM with poor glycaemic control and recurrent episodes of hypoglycaemias and diabetic ketoacidosis (DKA). Recurrent oromucosal and respiratory infections further complicated the course of illness, resulting in the increasing proneness to DKA. The patient was screened for coeliac disease but the IgA-based screening test was negative (IgA tissue transglutaminase) due to the low IgA level, whereas the IgG antigliadin was positive. The patient benefited from initiation of a gluten-free diet. PMID- 24214151 TI - Deconditioning the athletic heart. PMID- 24214152 TI - Dermoid cyst: an unusual location. PMID- 24214153 TI - Behcet's disease with major vascular involvement. AB - A 40-year-old Chinese man was admitted for haemoptysis and progressive deep vein thrombosis involving the inferior vena cava (IVC) despite anticoagulation. An IVC filter had been placed earlier at an outside hospital. CT angiography revealed two pulmonary artery aneurysms. The patient was found to have a history of oral and genital ulcers, uveitis and erythema nodosum, thus meeting criteria for Behcet's disease. Other causes of the haemoptysis and thrombophilia were excluded. He underwent successful coil embolisation of the pulmonary artery aneurysms and responded well to immunosuppressive therapy with cyclophosphamide and steroids. Anticoagulation was cautiously continued to limit the long-term risk of secondary thrombosis from his IVC filter. The patient remains well 5 months after initiation of immunosuppressive therapy. Making a diagnosis of Behcet's disease in the setting of thrombosis is crucial, as treatment must include immunosuppression, and, thus, fundamentally differs from the management of most other thrombotic disorders. PMID- 24214154 TI - Acute bilateral putaminal haemorrhagic necrosis in methanol poisoning. PMID- 24214155 TI - Isolated caecal tuberculosis mimicking a neoplastic tumour in an immunocompetent woman. AB - Although tuberculosis is endemic in Tunisia, only a few cases of intestinal disease have been reported. This entity is usually associated with pulmonary tuberculosis. Any part of the gastrointestinal tract may be affected but usually with ileocaecal involvement. Diagnosis is extremely difficult because the clinical presentation is so variable. The disease frequently mimics other chronic inflammatory intra-abdominal diseases or even malignancy. We report a case of isolated colonic tuberculosis presenting as circumferential ulcerovegetative lesions in the caecal region. PMID- 24214156 TI - Treatment of anxiety from musical obsessions with a cognitive behaviour therapy tool. AB - Musical obsessions and hallucinations are disturbing experiences of repeating internal music. Antipsychotic medication can sometimes reduce these symptoms but can also trigger or augment them. We report the case of a female patient with schizophrenia with drug-resistant obsessive musical hallucinations. The patient volunteered to participate in a 9-month pilot study to follow the development of the condition using an involuntary music and mood inventory. The patient perceived benefits from the intervention, including reduced anxiety, increased feeling of being in control and understanding the condition better. Findings from this case study suggest that cognitive therapy can be a useful complementary method of care for persons with musical obsessions. The presented tool requires further investigations among those with this rare condition. PMID- 24214157 TI - An unusual cause of sustained ventricular tachycardia in a 27-year-old man. AB - We present an interesting, unusual and complex case of a young man who initially presented with symptoms suggestive of tuberculosis and later developed malignant ventricular arrhythmias. A diagnosis of cardiac sarcoidosis was made only after histological evidence was paired with his presentation of monomorphic ventricular tachycardia. In this case we highlight the current challenges faced in the choice of investigations and diagnostic criteria. Additionally, we have identified the difficulties in treatment and long-term management of such a multisystem disorder. Ultimately by doing so, we hope to encourage clinicians to be aware of making a diagnosis of cardiac sarcoidosis. PMID- 24214158 TI - Peculiar MRI findings of intracranial hypotension in patients with abducens nerve palsy. PMID- 24214159 TI - Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey. AB - Neuroanatomical studies have long indicated that corticocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previously, two networks were recognized in the orbitomedial prefrontal cortex, the "orbital" and "medial" networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cortex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the networks. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas. PMID- 24214160 TI - Cost-effectiveness analyses of osteoarthritis oral therapies: a systematic review. AB - BACKGROUND: Cost-effectiveness analyses (CEAs) have been performed for oral non disease-altering osteoarthritis (OA) treatments for well over a decade. During that period the methods for performing these analyses have evolved as pharmacoeconomic methods have advanced, new treatments have been introduced, and the knowledge of associated adverse events (AEs) has improved. OBJECTIVE: The objective of this systematic review was to trace the development of CEAs for oral non-disease-altering treatments in OA. METHODS: A systematic search for CEAs of OA oral treatments was performed of the English-language medical literature using the following databases: PubMed, EMBASE, MEDLINE In-Process, EconLit, and Cochrane. Key requirements for inclusion were that the population described patients with OA or arthritis and that the analysis reported at least one incremental cost-effectiveness ratio. Each identified publication was assessed for inclusion. Thirteen characteristics and all AEs appearing in each included CEA were extracted and organized. Reference lists from these CEAs were also searched. A chronology of key CEAs in the field was compiled, noting the characteristics that advanced the state of the art in modeling oral OA treatments. RESULTS: Thirty publications of 28 CEAs were identified and evaluated. Developments in CEAs included an expanded set of comparators that broadened from non-steroidal anti-inflammatory drugs (NSAIDs) only to NSAIDs plus gastroprotective agents, cyclooxygenase-2 inhibitors, and opioids. In turn, AEs expanded from gastrointestinal (GI) events to also include cardiovascular (CV) and neurological events. Efficacy, which initially was presumed to be equivalent for all treatments, evolved to treatment-specific efficacies. Decision-tree analyses were generally replaced by Markov models or, occasionally, stochastic or discrete event simulation. Finally, outcomes have progressed from GI-centric measures to also include quality-adjusted life-years. CONCLUSION: Methods used by CEAs of oral non-disease-altering OA treatments have evolved in response to changing treatments with different safety profiles and efficacies as well as technical advances in the application of decision science to health care. PMID- 24214161 TI - Race, risk, and recreation in personal genomics: the limits of play. AB - Despite the mantra that genetics has moved beyond race, the burgeoning industry of genetic ancestry reveals how genetics has offered new technology through which individuals can link to intersections in time and space in complex ways that recapitulate understandings of racial order, origins, and group membership. This article focuses on the trope of "recreation" asserted in the marketing of ancestry genetic tests and examines the suggestion of self-discovery through the recovery of lost kin. Themes of recreation and re-creation paradoxically suggest both passivity of self-revelation and the power to re-act and re-create one's self in light of a different, more enlightened future. Direct-to-consumer personal genetics testing companies play guardian to this consumer play, providing tailored genetic scripts and highlighting how consumers might use their information. This article critically examines the play with concepts of ancestry, ethnicity, and genetic variation and their implications for public understanding of the relationship between race and genetics. PMID- 24214162 TI - Epoxides as reducing agents for low-catalyst-concentration atom transfer radical polymerization. AB - Activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) conditions utilizing a low concentration of catalyst are successfully applied for the preparation of well-defined poly(glycidyl methacrylate) without the addition of external reducing agents. The living character of polymerization is evidenced by successful chain extensions with methyl methacrylate and methyl acrylate, again, in the absence of additional reducing agents, yielding block copolymers. The epoxide groups in glycidyl methacrylate or the corresponding polymer can serve as an intrinsic reducing agent to continuously regenerate the Cu(I) -based ATRP activator from the Cu(II) halide complex present in the systems. The reactivity of various epoxides in the reduction of the Cu(II) Br2 complex of tris(2-pyridylmethyl)amine is compared. PMID- 24214163 TI - Structure-based design of an RNA-binding p-terphenylene scaffold that inhibits HIV-1 Rev protein function. PMID- 24214165 TI - An intervention for sensory difficulties in children with autism: a randomized trial. AB - This study evaluated a manualized intervention for sensory difficulties for children with autism, ages 4-8 years, using a randomized trial design. Diagnosis of autism was confirmed using gold standard measures. Results show that the children in the treatment group (n = 17) who received 30 sessions of the occupational therapy intervention scored significantly higher (p = 0.003, d = 1.2) on Goal Attainment Scales (primary outcome), and also scored significantly better on measures of caregiver assistance in self-care (p = 0.008 d = 0.9) and socialization (p = 0.04, d = 0.7) than the Usual Care control group (n = 15). The study shows high rigor in its measurement of treatment fidelity and use of a manualized protocol, and provides support for the use of this intervention for children with autism. Findings are discussed in terms of their implications for practice and future research. PMID- 24214166 TI - A thermoreversible poly(choline phosphate) based universal biomembrane adhesive. AB - A new monomer, 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl methacrylate (AEO4 MA), and its direct atom transfer radical polymerization (ATRP) into poly(AEO4 MA), then "clicked" with prop-2-ynyle choline phosphate (CP) to produce a poly(choline phosphate) are described. This polymer exhibits a lower critical solution temperature (LCST) at ~ 32 degrees C, and provides a universal thermally reversible biomembrane adhesive, which can rapidly both bind to any mammalian cell membrane and internalize into the cytoplasm of nucleated cells below the LCST. Moving above the LCST reverses cell surface binding. The use of ATRP implies that such polymers can be applied to modify the surfaces of a wide range of biomaterials. The capacity to bind and immobilize cells at room temperature and release them above the LCST should be particularly useful for in vitro cell manipulation and tissue engineering applications. PMID- 24214167 TI - Determination of monoisotopic masses and ion populations for large biomolecules from resolved isotopic distributions. AB - The coupling of electrospray ionization with Fourier-transform mass spectrometry allows the analysis of large biomolecules with mass-measuring errors of less than 1 ppm. The large number of atoms incorporated in these molecules results in a low probability for the all-monoisotopic species. This produces the potential to misassign the number of heavy isotopes in a specific peak and make a mass error of +/-1 Da, although the certainty of the measurement beyond the decimal place is greater than 0.1 Da. Statistical tests are used to compare the measured isotopic distribution with the distribution for a model molecule of the same average molecular mass, which allows the assignment of the monoisotopic mass, even in cases where the monoisotopic peak is absent from the spectrum. The statistical test produces error levels that are inversely proportional to the number of molecules in a distribution, which allows an estimation of the number of ions in the trapped ion cell. It has been determined, via this method that 128 charges are required to produce a signal-to-noise ratio of 3:1, which correlates well with previous experimental methods. PMID- 24214168 TI - Complete sequence confirmation of large peptides by high energy collisional activation of multiply protonated ions. AB - High energy collisional activation on a tandem four-sector mass spectrometer produces fragmentation throughout the peptide backbone of multiply protonated peptides in the 4-5-ku molecular weight range, which enables complete sequence confirmation from these peptides, including leucine-isoleucine determinations. The resolutions provided by this type of mass spectrometer permit the charge state of the fragment ions to be determined by identifying their isotopic spacing. This eliminates the complexity in spectral interpretation caused by the presence of fragment ions in various charge states. The reliable mass assignments from a sector mass spectrometer permit identification of amino acids that differ by as little as a single unit in these large peptides. The combination of excellent mass accuracy with the ability to assign charge states is expected to greatly facilitate the interpretation of tandem mass spectra from unknown peptides, and permit their sequences to be deduced. These results lead us to propose tandem mass spectrometric analysis of multiply charged precursor ions on a tandem four-sector instrument as a direct strategy for determination of the complete amino acid sequence of peptides up to 5 ku. PMID- 24214169 TI - Tandem mass spectrometric characterization of a specific cysteic acid residue in oxidized human apoprotein B-100. AB - The oxidation of low density lipoprotein (LDL) in vivo may result in its unregulated uptake by macrophages, with the consequent accumulation of cholesterol that is characteristic of the development of atherosclerosis. This paper describes initial experiments to elucidate structural changes that occur in an in vitro model of LDL oxidation. LDL was isolated from human blood and oxidized in the presence of copper ion. Lipid was removed and the isolated apoprotein was subjected to tryptic hydrolysis. The hydrolysate was separated by high performance liquid chromatography and individual fractions were screened by amino acid analysis to detect cysteic acid residues. Appropriate fractions were analyzed by fast atom bombardment mass spectrometry and hybrid tandem mass spectrometry. In this manner a tryptic fragment was identified that corresponded to residues 4187-4195 (EELCTMFIR), in which the cysteine and methionine residues were oxidized to cysteic acid and methionine sulfoxide, respectively. Identical analysis of LDL not subjected to in vitro oxidation revealed no evidence for this oxidized peptide. Earlier work established a surface location for this cysteine residue (Cys24) on the LDL particle, which suggested that its modification may significantly affect the properties of LDL, such as the propensity to intermolecular interaction via disulfide bridges. The analytical protocol developed here (involving proteolysis, screening of peptide fragments, and tandem mass spectrometry analysis) constitutes a strategy of general applicability to the characterization of targeted modifications of large proteins via mass spectrometry. PMID- 24214170 TI - Low energy tandem mass spectrometry of deoxynucleoside adducts of polycyclic aromatic hydrocarbon dihydrodiol-epoxides. AB - The use of fast-atom bombardment ionization-tandem mass spectrometry approaches, with collision energies on the order of 30-50 eV, was developed for the analysis of low picomole quantities of polycyclic aromatic hydrocarbon dihydrodiol-epoxide deoxynucleoside adducts. This strategy combines three experimental techniques: (1) product ion scans, (2) constant neutral loss scans, and (3) precursor ion scans. Product ion scans of the protonated molecule or the BH 2 (+) ion that results from loss of the deoxyribose were dominated by fragments associated with cleavage of the sigma bond between the dihydrodiol-epoxide moiety and the nucleobase. Constant neutral loss scans were based upon the loss of deoxyribose (116 u) or the combined loss of the deoxynucleoside, water, and carbon monoxide (313 u); precursor ion scans utilized the latter fragment. The formation of trimethylsilyl derivatives increased the sensitivity of analysis, which allowed the simultaneous detection of DNA adducts in a mixture. PMID- 24214171 TI - Design and performance of an in-line surface-induced dissociation device in a four-sector mass spectrometer. AB - A new in-line surface-induced dissociation device has been designed and characterized in a high performance four-sector tandem mass spectrometer. The design incorporates a target electrode parallel to the ion beam axis and an angled deflector plate (45 degrees relative to the ion beam) to provide large collision angles. In addition, an extraction electrode (parallel to the target electrode) is employed to efficiently extract product ions from the target surface. Results obtained with this device indicate high internal energy deposition (up to 16. 3 eV) as measured with the thermometer ions W(CO) 6 (+.) and Si(C2H5)4/+., as evidenced by extensive dissociation of the refractory pyrene molecular ion, and as indicated by the b 3/y 2 ratio in the product ion spectrum of leucine enkephalin. High resolution provided by the four-sector instrument for both precursor ions and product ions allows the observation of previously unobserved dissociation products in the surface-induced dissociation spectra of Si(C2H5)4/+. and novel ion-surface reaction products in spectra of W(CO)6/+. ions after collisions with hydrocarbon-covered surfaces. Both hydrogen atom and hydrocarbon abstraction products are observed. The dissociation efficiencies measured with the in-line device are approximately 1% when hydrocarbon-coated surfaces are used and increase fivefold with a fluorinated surface. PMID- 24214172 TI - Novel perfluoroacyl derivatives of corticosteroids and related substances for potential use in quantitative gas chromatography mass spectrometry. AB - We investigated the potential of perfluoroacylation for gas chromatographic mass spectrometric determination of corticosteroids and related substances. Structure elucidation of the reaction products was performed with high and low resolution mass spectrometry and with proton and carbon nuclear magnetic resonance spectrometry. Besides the well known 3-enol ester formation, 17beta-methyl-18-nor 13(14)-ene steroids were formed via loss of the 17-alpha hydroxyl group followed by a Wagner-Meerwein rearrangement. Compounds that bear an 11beta-hydroxy group formed additionally a 9(11) double bond when acetone was used as solvent, whereas acetonitrile or cyclohexane led to formation of 11beta-perfluoroacyl esters. In particular, perfluoroacylation of cortisol led to a clearly defined product instead of complex mixtures observed before, which thus makes it a valuable alternative to methoxime formation-silylation of cortisol for quantitative gas chromatographic mass spectrometric analyses. PMID- 24214174 TI - Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications. AB - Gold nanoparticles (AuNPs) can be readily synthesized and modified with chemical and biological molecules, making them attractive inorganic biomaterials for drug delivery and molecular diagnostics. The surface of AuNPs supports the efficient attachment of various biomacromolecules via chemisorption, chemical conjugation and electrostatic interaction. Based on advantages of facile surface modification and unique optical properties, AuNPs have been extensively used as drug carriers for the intracellular delivery of therapeutics as well as molecular nanoprobes for detection and monitoring of the target molecules of interest. In this review, we highlight advanced approaches in the biomedical applications of AuNPs such as gene and drug therapy, molecular diagnostics and imaging. PMID- 24214175 TI - Extracellular stability of nanoparticulate drug carriers. AB - Nanoparticulate (NP) drug carrier systems are attractive vehicles for selective drug delivery to solid tumors. Ideally, NPs should evade clearance by the reticuloendothelial system while maintaining the ability to interact with tumor cells and facilitate cellular uptake. Great effort has been made to fulfill these design criteria, yielding various types of functionalized NPs. Another important consideration in NP design is the physical and functional stability during circulation, which, if ignored, can significantly undermine the promise of intelligently designed NP drug carriers. This commentary reviews several NP examples with stability issues and their consequences, ending in a discussion of experimental methods for reliable prediction of NP stability. PMID- 24214176 TI - Combined corticosteroid and long-acting beta2-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. AB - BACKGROUND: Both long-acting beta2-agonists (LABA) and inhaled corticosteroids (ICS) have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease (COPD). Their coadministration in a combination inhaler may facilitate adherence to medication regimens and improve efficacy. OBJECTIVES: To determine the efficacy and safety of combined ICS and LABA for stable COPD in comparison with placebo. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, reference lists of included studies and manufacturers' trial registries. The date of the most recent search was June 2013. SELECTION CRITERIA: We included randomised and double-blind studies of at least four weeks' duration. Eligible studies compared combined ICS and LABA preparations with placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study risk of bias and extracted data. Dichotomous data were analysed as fixed-effect odds ratios (OR) or rate ratios (RR) with 95% confidence intervals (95% CI), and continuous data as mean differences with 95% confidence intervals. MAIN RESULTS: Nineteen studies met the inclusion criteria (with 10,400 participants randomly assigned, lasting between 4 and 156 weeks, mean 42 weeks). Studies used three different combined preparations (fluticasone/salmeterol, budesonide/formoterol or mometasone/formoterol). The studies were generally at low risk of bias for blinding but at unclear or high risk for attrition bias because of participant dropouts. Compared with placebo, both fluticasone/salmeterol and budesonide/formoterol reduced the rate of exacerbations. Mometasone/formoterol reduced the number of participants experiencing one or more exacerbation. Pooled analysis of the combined therapies indicated that exacerbations were less frequent when compared with placebo (Rate Ratio 0.73; 95% CI 0.69 to 0.78, 7 studies, 7495 participants); the quality of this evidence when GRADE criteria were applied was rated as moderate. Participants included in these trials had on average one or two exacerbations per year, which means that treatment with combined therapy would lead to a reduction of one exacerbation every two to four years in these individuals. An overall reduction in mortality was seen, but this outcome was dominated by the results of one study (TORCH) of fluticasone/salmeterol. Generally, deaths in the smaller, shorter studies were too few to contribute to the overall estimate. Further longer studies on budesonide/formoterol and mometasone/formoterol are required to clarify whether this is seen more widely. When a baseline risk of death of 15.2% from the placebo arm of TORCH was used, the three-year number needed to treat for an additional beneficial outcome (NNTB) with fluticasone/salmeterol to prevent one extra death was 42 (95% CI 24 to 775). All three combined treatments led to statistically significant improvement in health status measurements, although the mean differences observed are relatively small in relation to the minimum clinically important difference. Furthermore, symptoms and lung function assessments favoured combined treatments. An increase in the risk of pneumonia was noted with combined inhalers compared with placebo treatment (OR 1.62, 95% CI 1.36 to 1.94), and the quality of this evidence was rated as moderate, but no dose effect was seen. The three-year NNTH for one extra case of pneumonia was 17, based on a 12.3% risk of pneumonia in the placebo arm of TORCH. Fewer participants withdrew from the combined treatment arms for adverse events or lack of efficacy. AUTHORS' CONCLUSIONS: Combined inhaler therapy led to around a quarter fewer COPD exacerbations than were seen with placebo. A significant reduction in all-cause mortality was noted, but this outcome was dominated by one trial (TORCH), emphasising the need for further trials of longer duration. Increased risk of pneumonia is a concern; however, this did not translate into increased exacerbations, hospitalisations or deaths. Current evidence does not suggest any major differences between inhalers in terms of effects, but nor is the evidence strong enough to demonstrate that all are equivalent. To permit firmer conclusions about the effects of combined therapy, more data are needed, particularly in relation to the profile of adverse events and benefits in relation to different formulations and doses of inhaled ICS. Head-to-head comparisons are necessary to determine whether one combined inhaler is better than the others. PMID- 24214177 TI - Quantifying 'problematic' DIF within an IRT framework: application to a cancer stigma index. AB - PURPOSE: DIF detection within an IRT framework is highly powerful, often identifying significant DIF that is of little clinical importance. This paper introduces two metrics for IRT DIF evaluation that can discern potentially problematic DIF among items flagged with statistically significant DIF. METHODS: Computation of two DIF metrics-(1) a weighted area between the expected score curves (wABC) and (2) a difference in expected a posteriori scores across item response categories (dEAP)-is described. Their use is demonstrated using data from a 27-item cancer stigma index fielded to four adult samples: (1) Arabic (N = 633) and (2) English speakers (N = 324) residing in Jordan and Egypt, and (3) English (N = 500) and (4) Mandarin speakers (N = 500) residing in China. We used IRTPRO's DIF module to calculate IRT-based Wald chi-square DIF statistics according to language within each region. After standard p value adjustments for multiple comparisons, we further evaluated DIF impact with wABC and dEAP. RESULTS: There were a total of twenty statistically significant DIF comparisons after p value adjustment. The wABCs for these items ranged from 0.13 to 0.90. Upon inspection of curves, DIF comparisons with wABCs >0.3 were deemed potentially problematic and were considered further for removal. The dEAP metric was also informative regarding impact of DIF on expected scores, but less consistently useful for narrowing down potentially problematic items. CONCLUSIONS: The calculations of wABC and dEAP function as DIF effect size indicators. Use of these metrics can substantially augment IRT DIF evaluation by discerning truly problematic DIF items among those with statistically significant DIF. PMID- 24214178 TI - Fatigue in patients with spinal muscular atrophy type II and congenital myopathies: evaluation of the fatigue severity scale. AB - PURPOSE: The aim of this study was to evaluate whether the fatigue severity scale (FSS) is an appropriate instrument to assess fatigue in patients with spinal muscular atrophy type II (SMA II) and congenital myopathies (CM). METHODS: FSS and visual analog scale (VAS) were administered to 33 SMA II- and 72 CM patients. The psychometric properties of the FSS were evaluated by means of classical test theories for each of the disease groups. If abnormal fatigue was present in the disease group, the construct of fatigue was evaluated by means of focus group interviews. RESULTS: Fatigue was rare in SMA II patients, but very frequent in patients with CM. The cut-off score designating abnormal fatigue (FSS score >= 4) was exceeded by 10% of the SMA II patients in contrast to 76% of the CM patients, of whom 52% suffered from severe fatigue (FSS score >= 5). Focus group interviews demonstrated that fatigue had an adverse effect on motor function, level of energy, social relations, and identity, four themes that could be captured by the FSS. The FSS and VAS were strongly correlated in SMA II patients, but only moderately in CM patients. The psychometric properties indicated that the original FSS with nine items measures more than one construct of fatigue, eliminating the first two items improved scale properties. CONCLUSION: This study demonstrates that fatigue is characteristic in patients with CM, but not in patients with SMA II, in whom fatigue does not seem to impact daily life. While fatigue in CM and SMA II can be captured by FSS, omitting the first two items of the scale will improve its properties and content validity, along with comprehension of the scale itself. PMID- 24214179 TI - Development and testing of item response theory-based item banks and short forms for eye, skin and lung problems in sarcoidosis. AB - PURPOSE: Sarcoidosis is a multisystem disease that can negatively impact health related quality of life (HRQL) across generic (e.g., physical, social and emotional wellbeing) and disease-specific (e.g., pulmonary, ocular, dermatologic) domains. Measurement of HRQL in sarcoidosis has largely relied on generic patient reported outcome tools, with little disease-specific measures available. The purpose of this paper is to present the development and testing of disease specific item banks and short forms of lung, skin and eye problems, which are a part of a new patient-reported outcome (PRO) instrument called the sarcoidosis assessment tool. METHODS: After prioritizing and selecting the most important disease-specific domains, we wrote new items to reflect disease-specific problems by drawing from patient focus group and clinician expert survey data that were used to create our conceptual model of HRQL in sarcoidosis. Item pools underwent cognitive interviews by sarcoidosis patients (n = 13), and minor modifications were made. These items were administered in a multi-site study (n = 300) to obtain item calibrations and create calibrated short forms using item response theory (IRT) approaches. RESULTS: From the available item pools, we created four new item banks and short forms: (1) skin problems, (2) skin stigma, (3) lung problems, and (4) eye Problems. We also created and tested supplemental forms of the most common constitutional symptoms and negative effects of corticosteroids. CONCLUSIONS: Several new sarcoidosis-specific PROs were developed and tested using IRT approaches. These new measures can advance more precise and targeted HRQL assessment in sarcoidosis clinical trials and clinical practice. PMID- 24214180 TI - High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse. AB - Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT. PMID- 24214181 TI - Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-alpha and prevents early alcohol-induced liver injury in mice. AB - Although osteopontin (OPN) is induced in alcoholic patients, its role in the pathophysiology of alcoholic liver disease (ALD) remains unclear. Increased translocation of lipopolysaccharide (LPS) from the gut is key for the onset of ALD because it promotes macrophage infiltration and activation, tumor necrosis factor-alpha (TNFalpha) production, and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol induced liver injury. Wild-type (WT), OPN knockout (Opn(-/-)), and transgenic mice overexpressing OPN in hepatocytes (Opn(HEP) Tg) were fed either the control or the ethanol Lieber-DeCarli diet. Ethanol increased hepatic, plasma, biliary, and fecal OPN more in Opn(HEP) Tg than in WT mice. Steatosis was less in ethanol treated Opn(HEP) Tg mice as shown by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation score, and the number of macrophages and TNFalpha(+) cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed binding affinity for LPS which prevented macrophage activation, reactive oxygen, and nitrogen species generation and TNFalpha production. Treatment with milk OPN (m OPN) blocked LPS translocation in vivo and protected from early alcohol-induced liver injury. CONCLUSION: Natural induction plus forced overexpression of OPN in the liver or treatment with m-OPN protect from early alcohol-induced liver injury by blocking the gut-derived LPS and TNFalpha effects in the liver. PMID- 24214183 TI - The effect of rehabilitation on the rate of oxidation of pyrite in a mine waste rock dump. AB - Temperature profiles within a mine waste rock dump undergoing pyritic oxidation have been used to estimate the rate of oxidation and the sites where oxidation was occurring. The waste rock dump is located at the abandoned Rum Jungle mine site in Northern Australia and was a major source of pollution to the local river system. The dump was rehabilitated in 1983-84 by reshaping to reduce erosion and covering with clay and soil to reduce infiltration of water.Heat source distributions were derived from temperature profiles measured in the dump. The oxidation of pyritic material is the main cause of heat in the dump, hence the rate and location of oxidation can be obtained from the distribution of heat sources. A comparison of the heat source distributions before and after rehabilitation showed that rehabilitation greatly reduced or stopped the oxidation of pyrite in the dump. PMID- 24214182 TI - Over the counter drugs (and dietary supplement) exercise: a team-based introduction to biochemistry for health professional students. AB - For successful delivery of basic science topics for health-professional students, it is critical to reduce apprehension and illustrate relevance to clinical settings and everyday life. At the beginning of the Biochemistry course for Physician Assistants, a team-based assignment was designed to develop an understanding of the mechanism of action, effectiveness, and toxicity of five common over the counter (OTC) drugs and dietary supplements, and place these familiar medicines in a political and historical context. The objectives of this exercise were to stimulate interest in biochemistry; to provide basic information on enzymes and enzyme inhibitors related to these drugs to be expanded upon later in the course; and to encourage active and interactive learning. Teams of five students were formed, and each student was given an information sheet on aspirin, alpha-galactosidase, orlistat, dextromethorphan, or simvastatin, a low dose statin, which was previously available without prescription at pharmacies in the UK. After each member of the team acquired information on one OTC drug/dietary supplement by reading an assigned information sheet, the team was asked to go through a series of questions, and then submit answers to a quiz as a group. A high rate of success on the quiz, an overwhelmingly positive response on formal course evaluations, and enthusiastic exchanges during class suggested this team based session accomplished its goals. PMID- 24214184 TI - Lead and potential health risks from subsistence food crops in urban Kenya. AB - Lead, zinc and cadmium were analysed in a range of subsistence crops cultivated in and around Nairobi city centre. Lead was found to be the only contaminant of concern, being widely dispersed with elevated levels found in crops and soils from both suburban and city centre areas. Extremely high concentrations were recorded in the edible portions of a variety of crops, and high soil Pb levels were recorded within 30m of busy roads. Based on these data, it is estimated that subsistence on a diet of crops cultivated in and around Nairobi could increase Pb intake by 10-100 times the FAO/WHO maximum tolerable levels, potentially contributing substantially to existing health problems. PMID- 24214185 TI - Lead in food and the diet. PMID- 24214186 TI - The selenium status of sheep in Britain as indicated by wool selenium concentration. AB - A correlation between the selenium concentration in wool and blood erythrocyte glutathione peroxidase activity (GSHPx) from sheep in W. Derbyshire, a high selenium area and N. Wales and Romney Marsh, low/marginal selenium areas is reported.Soil and herbage selenium concentrations were significantly correlated with wool selenium levels and GSHPx activity.A significant difference was found between wool selenium concentrations and between GSHPx activities from sheep in W. Derbyshire and those animals sampled in N. Wales and Romney Marsh. 90% of wool samples from the low/marginal areas gave concentrations below 0.125 MUg Se/g. 6.125 MUg Se/g wool is suggested as a threshold value for selenium in wool from sheep grazing low/marginal areas.Seasonal peaks in wool selenium concentrations and GSHPx activities are found in March and June respectively. Supplementary feeds, which contain added selenium, given to livestock during the winter season may be responsible for these seasonal differences.GSHPx activity data reported in this study records higher sheep selenium levels than those reported in the 1979 survey by Andersonet al. This increase is attributed to the addition since 1979 of selenium to feeds and drenches.Wool is proposed as an accurate and less costly measure of sheep selenium status. PMID- 24214189 TI - QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. AB - A QT/QTc study was conducted in compliance with ICH E14 guideline to evaluate the effects of a new xanthine oxidase inhibitor topiroxostat in Japanese healthy subjects. Forty-eight Japanese healthy subjects (males 24; females 24) received a single oral dose of topiroxostat (60 or 180 mg), moxifloxacin (400 mg) or placebo in a single-center, double-blind, four-period crossover design. Fridericia's formula (QTcF = QT/RR(0.33) ) was used as a primary method for QT-interval correction. The mean QTcF was prolonged by moxifloxacin, of which largest time matched difference from placebo administration was 13.6 milliseconds with 90% confidence interval (CI) of 11.2 and 15.9 milliseconds at 4 hours post-dose. The mean QTcF was hardly affected by either dose of topiroxostat, of which largest time-matched difference from placebo administration was 2.9 milliseconds with 90% CI of 0.6 and 5.3 milliseconds at 4 hours post-dose for 60 mg, and 2.3 milliseconds with 90% CI of 0 and 4.7 milliseconds at 1 hour post-dose for 180 mg. The results were essentially the same in the sex subgroup analysis. Moxifloxacin can be used as a positive control for QT/QTc studies in Japanese subjects; and topiroxostat may not cause QT-interval prolongation in males as well as females. PMID- 24214190 TI - Digestive enzyme activities and their distribution in the alimentary canal of larvae of the three extant lamprey families. AB - The activities of trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), lipase (EC 3.1.1.3) and amylase (EC 3.2.1.1) were measured in different regions of the alimentary tract of ammocoetes from each of the three extant lamprey families. In the southern hemisphere speciesGeotria australis (Geotriidae), and even more particularlyMordacia mordax (Mordaciidae), enzymatic activity was almost entirely confined to prominent diverticular extensions which arise at the oesophageal intestinal junction. However, in the holarcticLampetra richardsoni (Petromyzontidae), which does not possess a diverticulum, the enzymatic activity was highest in the upper anterior intestine. It is not clear whether the presence of significantly higher amylolytic and lower lipolytic activities in the diverticulum ofG. australis than in the exocrine tissue of the other two species reflects interspecific differences in the composition of their diets. The capacity of exocrine tissue extracts for chymotryptic and tryptic digestion was assayed before and afterin vitro exposure to trypsin and enteropeptidase, their respective catalytic activators. Prior to exposure to these exogenous activators, both proteolytic enzymes were fully active inL. richardsoni, partially active inG. australis and totally inactive inM. mordax. Maximal chymotryptic activity was greater inM. mordax than inL. richardsoni andG. australis. In contrast, maximal tryptic activity was greater inL. richardsoni than inG. australis and was very low inM. mordax. Since trypsin is the only known activator of chymotrypsinogen, the negligible activity of trypsin inM. mordax would appear anomalous unless a trypsin inhibitor is present in the protopancreas of this species. Differences in the distribution of enzymatic activity within the alimentary tract of the three species is discussed in relation to proposed phylogenetic relationships amongst the extant lamprey families. PMID- 24214191 TI - Effect of feeding and fasting on plasma tryptophan and tryptophan to large neutral amino acid ratio, and on brain serotonin turnover in rainbow trout,Oncorhynchus mykiss. AB - Two time-course experiments were conducted to determine the effect of feeding and fasting on the plasma ratio of tryptophan (trp) to the large neutral amino acids (LNAA), (trp/LNAA ratio) and brain serotonin (5-HT) turnover in rainbow trout,Oncorhynchus mykiss. Trout were fasted overnight or for 3 days and were then either fed or continued to be fasted for up to a further 3 days. Changes in plasma trp, plasma trp/LNAA ratio, brain trp, brain 5-HT, brain 5 hydroxyindoleacetic acid (5-HIAA) and brain 5-HIAA/5-HT ratio were determined over time. Feeding decreased the plasma trp/LNAA ratio, brain trp and the brain 5 HIAA/5-HT ratio. In addition, in fish sampled over 3 days, there appeared to be a rhythm in plasma trp and the brain 5-HIAA/5-HT ratio which was independent of feeding. These results indicate that in rainbow trout, feeding is a sufficient physiological event to decrease brain 5-HT turnover. Furthermore, feeding independent changes in the brain 5-HIAA/5-HT ratio, which were evident in fasted fish sampled over 3 days, also suggest an additional, non-feeding-related modulator(s) of brain 5-HT turnover in rainbow trout. PMID- 24214192 TI - Protein synthesis in trout liver is stimulated by both feeding and fasting. AB - The response of protein synthesis in the liver of the rainbow trout to feeding and fasting was investigated in 3 experiments. In the first experiment, the fractional rate of protein synthesis (k s ), %/day) appeared to cycle with daily feeding events being increased by 46%, 123%, and 72% at 1.5h, 3h, and 6h, after a meal. In Experiment 2, liver protein synthesis fell progressively with fasting to a basal level at 4d which was only 20% of the value at 3h after feeding. Liver weight (hepatosomatic index, HSI, % body weight), total RNA and total protein also fell gradually. Between 4d and 6d, both the RNA/protein ratio and the rate of protein synthesis were significantly increased (11% and 74%). At this time, however, there was also a large loss of liver protein suggesting a concomitant increase in protein breakdown. In the last experiment, when trout were pre-fed a low ration (0.6%/d for 2 wks, LR group), the HSI and liver total RNA and protein were largely unaffected by the 6d fast (i.e., relative to the body weight). In this group, however, protein synthesis at 3h was significantly higher than in fish pre-fed a high ration (1.5%/d, HR group). In addition, at 6d after feeding, protein synthesis had increased back to fed levels in the LR group only. It is concluded that protein synthesis in the liver of the trout is influenced both by feeding events and by ration size and also by the degree to which the trout is fasted. PMID- 24214193 TI - Requirement for tryptophan by milkfish (Chanos chanos Forsskal) juveniles. AB - Groups of milkfish juveniles (mean initial weight 7.7 g) were fed semipurified diets containing 0.9, 1.4, 2.1, 3.1, 4.1 and 6.1 g tryptophan/kg dry diet for 12 weeks. The mean crude protein content of the diets (containing white fishmeal, gelatin and free amino acid mixture to simulate the pattern of hydrolysed milkfish protein) was 49%. On the basis of the growth response, the tryptophan requirement of milkfish juveniles was estimated to be 3.1 g/kg diet. Fish fed low levels of tryptophan exhibited low weight gains and poor feed conversion ratios. Survival (92-100%) was consistently high in all treatments. Fish fed diets containing tryptophan levels greater than 3.1 g/kg had slightly lower survival rates. The activity of hepatic tryptophan pyrrolase showed no significant differences with increasing dietary tryptophan levels. No nutritional deficiency signs were observed other than the depression in growth rates in fish given the tryptophan deficient diets. PMID- 24214194 TI - Metallothionein induction in cultured fibroblasts and liver of a marine flatfish, the turbot,Scophthalmus maximus. AB - Intraperitoneal injection of turbot with Cd induced the synthesis of a low molecular weight hepatic Cd-binding protein and a 500bp mRNA, which hybridised to a plaice metallothionein (MT) cRNA probe. The Cd-binding protein displayed cross reactivity in a competitive ELISA with antiserum raised against rainbow trout MT and had the characteristic amino acid composition, metal stoichiometry and spectral characteristics of a Class I MT. Only one isoform was apparent on ion exchange chromatography. Southern blot analysis of DNA cleaved with four restriction enzymes suggested that only a single MT gene is present in turbot.In an established turbot fibroblast cell line, Cd induced MT mRNA and MT levels in a dose and time-dependent manner. MT was also induced by Cu, Hg and Zn but not Pb exposure. Physiological concentrations of glucocorticoids and sex hormones did not induce MT synthesis, although at high concentrations a positive response to corticosterone, dexamethasone, hydrocortisone or progesterone was observedin vitro indicating the possible presence of a functional steroid regulatory element in the fish MT gene. PMID- 24214195 TI - The biliary accumulation of corticosteroids in rainbow trout,Oncorhynchus mykiss, during acute and chronic stress. AB - The accumulation of immunoreactive corticosteroids in the bile of rainbow trout during stress was monitored by radioimmunoassay and GUMS. Although plasma cortisol levels were elevated by confinement for 1 hour, biliary levels of free and conjugated steroids in the bile were unaffected. However, after 24 hours confinement, in addition to elevated plasma cortisol levels, free and conjugated steroids in the bile were also significantly higher than in control, unstressed fish. The time-course of change in plasma and biliary corticosteroid levels was determined in rainbow trout subject to 96 hours confinement stress. Free steroid levels in the bile of stressed fish were elevated within 2 hours of the onset of stress, while levels of conjugated steroids were significantly elevated within 4 hours of the onset of confinement. Analysis of bile from stressed fish, by GC/MS, established the major conjugated steroids present to be tetrahydrocortisone (230 MUg ml(-1) bile), tetrahydrocortisol (75 MUg ml(-1)), cortisone (33.5 MUg ml( 1)), cortisol (25 MUg ml(-1)) and beta-cortolone (5 MUg ml(-1)). The data are discussed with reference to the role of cortisone and conjugating enzymes in the clearance of cortisol, and further data are presented to suggest that the analysis of biliary steroid content may provide a suitable means of identifying stressed fish under conditions in which an additional sampling stress is unavoidable. PMID- 24214196 TI - Plasma growth hormone levels in fed and fasted rainbow trout (Oncorhynchus mykiss) are decreased following handling stress. AB - Plasma growth hormone concentrations of rainbow trout,Oncorhynchus mykiss, fasted for six weeks, were significantly (p < 0.01) higher than in comparable fed animals; in the fasted fish, the levels fell progressively following acute stress (by displacing the fish within their home aquarium), with significant differences from pre-stressed fish evident between one and thirty-two hours after application of the stressor. Plasma growth hormone concentrations also fell significantly in the fed group, but differences were evident only between two and eight hours after stressor application.Plasma cortisol concentrations in pre- and post stressed fed and fasted fish were similar. There was a bimodal response to stressor application in both groups, with significantly higher values relative to the pre-stressed sample evident one and eight hours after disturbance, but not after two, four or thirty-two hours. The changes in plasma cortisol levels between the initial (09:00h) sample and the sample taken eight hours later resembles the diet pattern seen in trout given access to self-demand feeders.Plasma glucose concentrations in pre-stressed fed animals were higher than in pre-stressed fasted fish. This relationship was also evident between one and four hours and thirty-two hours after stressor application. The post-stress rise in plasma glucose concentration was evident between one and four hours in the fed group, and between four and eight hours in fasted fish.The diel changes in plasma growth hormone and glucose concentrations could not be attributed to normal circadian patterns, and there was no apparent correlation between changes in plasma growth hormone and cortisol concentrations. There was a significant inverse correlation between plasma glucose and growth hormone concentrations when the total data set were analyzed, but these correlations were not apparent when the treatment groups were analyzed separately. PMID- 24214197 TI - Effects of ambient ion concentrations on gill ATPases in fresh water eel,Anguilla anguilla. AB - Branchial activities of Na(+),K(+)-ATPase (ouabain sensitive), Mg(2+) ATPase (ouabain insensitive) and kinetic analysis of high and low affinity Ca(2+) ATPase were measured inAnguilla anguilla that had been acclimated to demineralized water (DW, Ca < 10 MUM), freshwater (FW, Ca = 2 mM), and Low calcium freshwater (L-Ca, Ca = 0.9 mM). Na(+),K(+)-ATPase activity decreased while ouabain insensitive activity increased when ambient Ca(2+) decreased. Two kinetic forms of Ca(2+) ATPase could be resolved in each environmental condition. The stimulation coefficients of both sites or enzymes were not affected by ambient Ca(2+) concentrations. The maximal velocity of both the high and the low affinity Ca(2+) ATPase was increased when external Ca(2+) was decreased during acclimation. The low affinity Ca(2+) ATPase and the Mg(2+) stimulated enzyme could be a non specific enzyme accepting either Ca(2+) or Mg(2+). Results are compared with previous results in the literature and in relation to the branchial morphology and ionic exchanges in fish. PMID- 24214198 TI - For the sake of others: reciprocal webs of obligation and the pursuit of transplantation as a caring act. AB - This article highlights reciprocal webs of care and moral obligations toward kin during transplantation, using an expansive notion of "care" to include both its obvious and more hidden forms. Evidence from 24 months of ethnographic fieldwork among transplant patients, their loved ones, and clinical personnel in the U.S. Midwest suggests that patients are simultaneously caregivers to others and are considered vital members of reciprocal webs of care without whom their kin networks could not effectively operate. Transplantation can become a person's main, perhaps only hope of fulfilling ongoing obligations to others, so pursuing a transplant becomes not a matter of choice, but rather a moral orientation. A potential implication of these findings is that rather quotidian and conventional (even if contested) notions of what kin ought to do and be for each other may be among the underpinnings of high-tech biomedical practices like transplantation. PMID- 24214200 TI - Connectivity of somatosensory cortical area 1 forms an anatomical substrate for the emergence of multifinger receptive fields and complex feature selectivity in the squirrel monkey (Saimiri sciureus). AB - Converging evidence shows that interaction of digit-specific input, which is required to form global tactile percepts, begins as early as area 3b in the primary somatosensory cortex with the involvement of intrinsic lateral connections. How tactile processing is further elaborated in area 1, the next stage of the somatosensory cortical hierarchy, is less understood. This question was investigated by studying the tangential distribution of intrinsic and interareal connections of finger representations of area 1. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches were plotted and quantified with respect to the hand representation by combining tract tracing with electrophysiological mapping and intrinsic signal optical imaging in somatosensory areas. Intrinsic connections of distal finger pad representations of area 1 spanned the representation of multiple digits indicating strong cross digit connectivity. Area 1 distal finger pad regions also established high density connections with homotopic regions of areas 3b and 2. Although similar to area 3b, connections of area 1 distributed more widely and covered a larger somatotopic representation including more proximal parts of the finger representations. The lateral connectivity pattern of area 1 is a suitable anatomical substrate of the emergence of multifinger receptive fields, complex feature selectivity, and invariant stimulus properties of the neurons. PMID- 24214201 TI - Effect of laparoscopic Roux-en-Y gastric bypass on body composition and insulin resistance in Chinese patients with type 2 diabetes mellitus. AB - BACKGROUND: This study aims to assess the effect of laparoscopic Roux-en-Y gastric bypass (LRYGB) on body composition, fat distribution, and insulin resistance (IR) in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: Eighteen patients with T2DM were studied before and 3 months post LRYGB. Fasting plasma glucose (FPG), fasting insulin (FINS), and triglyceride (TG) were measured. IR index was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Body composition and fat distribution were measured by dual-energy X-ray absorptiometry (DXA). Fat mass (FM), muscle mass (MM), bone mineral content (BMC), and percent fat mass (%FM) at the whole body and five body regions including the arms, legs, trunk, android, and gynoid were obtained from DXA scans. RESULTS: HOMA-IR decreased from 5.02 at baseline to 1.43 3 months post LRYGB (p < 0.05). There was significant decrease in total and regional body mass and body fat (all p < 0.05). A significant reduction was observed in %FM at every tested body region (all p < 0.05). There was more fat mass loss (31.03 %) in android region than any other tested body region. Preoperative android %FM was significantly correlated with IR (r = 0.49, p < 0.05). Changes in android FM showed significant correlations with changes in IR, FPG, FINS, and TG (r = 0.54, 0.64, 0.54, and 0.67, respectively; all p < 0.05). CONCLUSIONS: Body composition in Chinese T2DM patients is rebalanced after LRYGB. Reduction of central obesity can result in improvement of IR, and android fat distribution may be a good indicator of postoperative benefits for LRYGB. PMID- 24214202 TI - Early impact of bariatric surgery on type II diabetes, hypertension, and hyperlipidemia: a systematic review, meta-analysis and meta-regression on 6,587 patients. AB - BACKGROUND: This study aims to evaluate the 12-24-month impact of bariatric surgery on the foremost modifiable traditional risk factors of cardiovascular disease. METHODS: A systematic review and meta-analysis of prospective interventional studies reporting the most commonly performed laparoscopic surgical procedures, i.e., Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and cardiovascular risk reduction after surgery. RESULTS: The bibliographic research conducted independently by two authors yielded 18 records. When looking at RYGB and AGB separately, we observed a relevant heterogeneity (I (2) index >=87 %) when BMI reduction was considered as the main outcome. When hypertension, type II diabetes, and hyperlipidemia risk reduction was estimated, a highly significant beneficial effect was found. The risk reduction was 0.33 [0.26; 0.42] for type II diabetes, 0.52 [0.42; 0.64] for hypertension, and 0.39[0.27; 0.56] for hyperlipidemia (P < 0.0001 for all outcomes considered). When looking at surgical technique separately, a higher but not statistically significant risk reduction for all outcomes considered was found. Results from the meta-regression approach showed an inverse relation between cardiovascular risks and BMI reduction. CONCLUSIONS: The present study showed an overall reduction of cardiovascular risk after bariatric surgery. According to our analysis a BMI reduction of 5 after surgery corresponds to a type II diabetes reduction of 33 % (as reported by Peluso and Vanek (Nutr Clin Pract 22(1):22-28, 2007); SAS Institute Inc., (2000-2004)), a hypertension reduction of 27 % (as reported by Buchwald and Oien (Obes Surg 23(4):427-436, 2013); Valera-Mora et al. (Am J Clin Nutr 81(6):1292-1297, 2005)), and a hyperlipidemia reduction of 20 %(as reported by Adams et al. (JAMA 308(11):1122-31, 2012)); Alexandrides et al. (Obes Surg 17(2):176-184, 2007). In summary, our study showed that laparoscopic bariatric surgery is an effective therapeutic option to reduce the cardiovascular risk in severe obese patients. PMID- 24214204 TI - Oxidative dehydrogenation on nanocarbon: identification and quantification of active sites by chemical titration. PMID- 24214203 TI - Prevalence and predictors of atrial fibrillation among patients undergoing bariatric surgery. AB - BACKGROUND: While AF is a disease of the elderly, it can occur earlier in the presence of risk factors such as obesity. Bariatric surgery patients are significantly younger and more obese than previously described populations with AF. Therefore, it remains to be determined whether current estimates of the prevalence and predictors for AF remain true in the bariatric surgery population. METHODS: We performed a cross-sectional analysis of 1,341 consecutive patients who underwent bariatric surgery from January 2008 to October 2012. Baseline characteristics were compared between patients with and without AF. For additional comparison, 176 patients with AF and body mass index (BMI) >40 kg/m(2) were identified from the Vanderbilt AF Registry. A multivariable logistic regression was performed to identify predictors of AF within the bariatric surgery cohort. RESULTS: The prevalence of AF in the bariatric surgery cohort was 1.9 % (25/1,341). Patients with AF were older (median 56 years (interquartile range [52-64) vs.46 [38-56] years, p < 0.001), were more often male (48 vs. 23 %, p = 0.004), had more comorbidities, but had no difference in BMI (50 kg/m(2) [44 58] vs. 48 [43-54], p = 0.4). In multivariable analysis, the odds of AF increased 2.2-fold by age per decade (95 % CI, 1.4-3.5; p < 0.001) and 2.4-fold by male gender (1.1-5.4, p = 0.03) when adjusted for BMI. BMI was not independently associated with AF (OR 1.15 [95 % CI, 0.98-1.41], p = 0.09). CONCLUSIONS: The prevalence of AF is 1.9 % among patients undergoing bariatric surgery. Risk of AF was found to increase with age and male gender, but not with higher BMI. PMID- 24214206 TI - A quantitative comparison between diet and body fatty acid composition in wild northern pike (Esox lucius L.). AB - The fatty acid compositions of wild female northern pike (Esox lucius L.) and their principle prey species were compared to assess the extent to which pike modify the relative abundance of dietary fatty acids during assimilation and to indicate the optimum dietary content of essential fatty acids (EFAs) for pike. Only minor differences existed between the estimated whole body fatty acid composition of pike and diet fatty acid composition as calculated from the contribution of each prey species to the pike's diet. Saturated fatty acids comprised a slightly higher percentage of diet lipids (25% wt) than of pike lipids (21% wt) whereas monounsaturated fatty acids were less abundant in diet lipids (26% wt) than in pike (29% wt). Percentages of total polyunsaturated fatty acids (PUFAs), n - 3 fatty acids, and n - 6 fatty acids were approximately 43, 30, and 13% wt respectively and differed by less than 1% wt between pike and diet lipids. Among individual PUFAs, the largest differences occurred in 20:5 (n-3) and 22:6(n-3) which comprised, on average, 9.6 and 14.7% wt respectively of diet lipids and 5.9 and 18.3% wt respectively of pike lipids. The close similarity in fatty acid composition between pike and their diet suggests that pike may have limited abilities to elongate and desaturate 18 carbon PUFAs and may require specific long chain PUFAs in the diet. The n-3 PUFA content of the pike's natural diet may exceed the minimum EFA requirements of better studied species such as rainbow trout and turbot. PMID- 24214207 TI - The incorporation and metabolism of polyunsaturated fatty acids in phospholipids of cultured cells from chum salmon (Oncorhynchus keta). AB - The incorporation and metabolism of (n-3) and (n-6) polyunsaturated fatty acids were studied in a cell line derived from chum salmon heart (CHH-1). Supplementing media with 25 MUM fatty acid considerably altered the cellular fatty acid composition but did not affect the lipid class composition or cause the appearance of cytoplasmic lipid droplets. CHH-1 cells exhibited considerable Delta-6-desaturase activity but showed no preference between (n-3) and (n-6)PUFA substrates. CHH-1 cells also possess Delta-5-desaturase activity which showed preference towards (n-3)PUFA, but Delta-4-desaturase activity was totally absent. Elongation of 20-carbon PUFA was especially active in CHH-1 cells with 22-carbon PUFA being specifically incorporated into PE and PS lipid classes. The fatty acid composition of PI indicated specific incorporation of 20-carbon PUFA into this lipid class. Supplementation with 22:6(n-3) generated fatty acid compositions more closely resembling those of intact salmonid hearts. Substantial chain shortening of 22:6(n-3) to 20:5(n-3) occurred. PMID- 24214205 TI - Wnt-signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans. AB - During the development of the nervous system, neurons encounter signals that inform their outgrowth and polarization. Understanding how these signals combinatorially function to pattern the nervous system is of considerable interest to developmental neurobiologists. The Wnt ligands and their receptors have been well characterized in polarizing cells during asymmetric cell division. The planar cell polarity (PCP) pathway is also critical for cell polarization in the plane of an epithelium. The core set of PCP genes include members of the conserved Wnt-signaling pathway, such as Frizzled and Disheveled, but also the cadherin-domain protein Flamingo. In Drosophila, the Fat and Dachsous cadherins also function in PCP, but in parallel to the core PCP components. C. elegans also have two Fat-like and one Dachsous-like cadherins, at least one of which, cdh-4, contributes to neural development. In C. elegans Wnt ligands and the conserved PCP genes have been shown to regulate a number of different events, including embryonic cell polarity, vulval morphogenesis, and cell migration. As is also observed in vertebrates, the Wnt and PCP genes appear to function to primarily provide information about the anterior to posterior axis of development. Here, we review the recent work describing how mutations in the Wnt and core PCP genes affect axon guidance and synaptogenesis in C. elegans. PMID- 24214208 TI - Circadian pattern of hepatosomatic index, liver glycogen and lipid content, plasma non-esterified fatty acid, glucose, T3, T 4, growth hormone and cortisol concentrations in Oncorhynchus mykiss held under different photoperiod regimes and fed using demand-feeders. AB - The circadian patterns of several tissue and plasma metabolites, and several plasma hormone concentrations are described in rainbow trout (Oncorhynchus mykiss) that were held in groups under three different photoperiod regimes, and given free access to a demand-feeder. Regardless of photoperiod regime, all the measured parameters showed significant diel rhythms that appeared to be synchronized by dawn; dawn was represented by the concomitant onset of both light and feeding. The diel increases in hepatic glycogen content, and plasma T4 and cortisol concentrations were in phase with the main period of feeding activity, whereas the peaks in plasma T3 and glucose concentrations that may also be triggered by feeding activity, were delayed by several hours. The peaks in hepatosomatic index, plasma non-esterified fatty acids and plasma growth hormone concentrations were 180 degrees out of phase with the main period of feeding activity, and associated with periods of hypophagia and low activity. PMID- 24214209 TI - Qualitative modification of muscle metabolic organization with thermal acclimation of rainbow trout, Oncorhynchus mykiss. AB - Rainbow trout (Oncorhynchus mykiss) were acclimated to 4 and 18 degrees C and fed at rations levels which led to an equal change in mass at these temperatures during the six week acclimation. Thermal acclimation markedly modified the metabolic organization of red and white muscle. Cold-acclimated fish had activities of beta-hydroxyacyl CoA dehydrogenase in both red and white muscle that were twice those of warm-acclimated fish. By contrast, the activities of cytochrome oxidase were unchanged by thermal acclimation. Thus, the capacity for beta-oxidation of lipids is specifically enhanced in the muscle of cold acclimated trout. In white muscle, citrate synthase and phosphofructokinase activities were also enhanced by cold acclimation (increases of 125% and 35% respectively), while cytochrome oxidase levels were unchanged. The non-parallel changes in the activities of mitochondrial enzymes strongly suggest that trout muscle mitochondria undergo qualitative reorganization during cold acclimation. The relative activities of mitochondrial enzymes suggest that mitochondria from red muscle have a threefold greater capacity to oxidize lipids than those from white muscle. PMID- 24214210 TI - Myosin, parvalbumin and myofibril expression in barbel (Barbus barbus L.) lateral white muscle during development. AB - Histo- and immunohistochemical techniques have recently been used to study the fibre type and myosin expression in fish muscle during development. In the present work, embryonic, larval and adult myosin isozymes (heavy and light chains) and parvalbumin isotypes were analyzed, from fertization to the adult stage, by polyacrylamide gel electrophoresis of barbel (Barbus barbus L.) trunk muscle extracts. The examined myosins display the sequential transitions from embryonic to larval and adult forms characteristic of higher vertebrates. They are characterized by specific heavy chains but their light chains differ only by the LC1/LC3 stoichiometry with LC3 exceeding LC1 after 10 days. Sarcoplasmic parvalbumins show considerable and unforeseen developmental transitions in their isotype distribution: the PA II isotype first appears after hatching and becomes the predominant form until the length reaches about 6 cm. One month after hatching, the amount of PA II then decreases and the synthesis of PA III and IV further increases to reach the typical adult pattern at a size of 18 cm. These observations show that the distribution of parvalbumin isotypes reflects the stage of development. It suggests a specific role for each isotype in relation to muscle activity. Microscopy illustrates the progressive development of somites, muscles cells, and myofibrils, which accelerates at hatching when movements increase. PMID- 24214211 TI - Effect of low sea water temperature on water balance in the Atlantic salmon, (Salmo salar L.). AB - The water balance in Atlantic salmon (Salmo salar L.) overwintering in sea water (34 0/00) was investigated. With a decrease of temperature from 5.6 to 1.0 degrees C the drinking rate decreased from 13.9 to 5.7 ml/kg/day, and the absolute amount of water absorbed decreased from 8.9 to 5.0 ml/kg/day. A decrease in temperature led, however, to an increase in the proportion of water absorbed in the intestines from 60 to 96%. Blood serum osmolarity increased from 320 to 440 mosm/1 with decreasing temperature and there was a reduction in tissue water content from 75 to 69% The disturbance of water balance at low temperature may be one of the factors responsible for mortality of salmon overwintering in sea water. PMID- 24214212 TI - Swimming performance, whole body ions, and gill Al accumulation during acclimation to sublethal aluminium in juvenile rainbow trout (Oncorhynchus mykiss). AB - Juvenile rainbow trout (2-5 g) were chronically exposed (for 22 days) to acidified softwater (Ca(2+) = 25 MUEq/l, pH 5.2) in the presence or absence sublethal Al (30 MUg/l). Al-exposed fish (5.2/Al group) suffered 20% whole body Na(+) and Cl(-) losses and a 30% reduction in the maximum sustainable swimming speed (Ucrit) over the initial 7 days. These disturbances were approximately 2 fold greater than those observed in the fish exposed to low pH alone (5.2/0 group). However, whole body ion levels were completely restored in the 5.2/Al fish by day 22, whereas they merely stabilized at a new reduced level in the 5.2/0 group. Increased resistance to acutely lethal Al (200 MUg/l at pH 5.2) was observed from day 17 onwards in the 5.2/Al fish. Despite this acclimation and recovery of whole body ions, Ucrit remained significantly lower than in the 5.2/0 group throughout. Growth on a restricted diet of 1% body wt. /day was normal in the 5.2/0 group compared with controls maintained in pH 6.5 softwater, whereas 5.2/Al fish suffered a 50% reduction in growth rate on the same diet. The 5.2/Al fish accumulated large amounts of Al on the gills, reaching an initial peak after 4 days, followed by a decline at 7 days, and a secondary rise thereafter. Therefore acclimation and recovery of whole body ionic status was not associated with a reduction in the gill Al burden. Some of the metabolic costs of acclimation to Al, namely a continued impairment of swimming speed and growth, are discussed in light of the physiological and structural changes reported to occur at the gills. PMID- 24214213 TI - Drinking behaviour in sea water and fresh water teleosts, the role of the renin angiotensin system. AB - Basal drinking rate and responses to administered angiotensin were examined in 12 species of fish. The responses of representative euryhaline, stenohaline marine and fresh water species to pharmacological manipulation of endogenous renin angiotensin system (RAS) activity were also investigated.Basal drinking rates were consistently low in stenohaline and euryhaline fresh water fish, and all species examined showed an increased imbibition in response to administered angiotensin. Marine fish drank large volumes of water, rates varying considerably between species, with euryhaline species exhibiting lower rates than stenohaline groups. The extremely high drinking rates observed in the sea scorpion were associated with a high plasma osmolality. With the exception of the sea scorpion, all other species examined in sea water showed a further rise in drinking in response to exogenous angiotensin.Although the freshwater stenohaline carp showed a dipsogenic response to angiotensin, it was apparently unable to evoke this response when fish were acclimated to brackish water. The high drinking rates of both euryhaline and stenohaline fish held in sea water appeared dependent upon an activated endogenous RAS, and were lowered following inhibition of Al to All conversion by Captopril. Drinking was further stimulated in these marine species following stimulation of endogenous RAS activity by the administration of the hypotensive agent Papaverine. The study endorses a role for the RAS in the control of adaptive drinking in euryhaline and stenohaline marine teleosts. PMID- 24214214 TI - Gill morphometry of the red drum, Sciaenops ocellatus. AB - The structure and morphometry of the gills of the marine teleost, red drum, have been studied. The present analysis of gas exchange area of fish gills is one of the most intensive and the results are compared to less intense averaging methods. Based on the gill area estimates, red drum falls into the category of a fish of intermediate activity. Its gill clearly has an exchange area less than that of the tunas, but is slightly greater than that of trout or bass. The three components that contribute to total exchange area (filament length, lamellar density, and area of individual lamellae) are not all greater in species with a greater total exchange area. The best correlate is total filament length. PMID- 24214215 TI - How do we process event-based and time-based intentions in the brain? an fMRI study of prospective memory in healthy individuals. AB - Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event-based) or after a certain amount of time has elapsed (time-based). While the distinction between event- and time based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event-based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event-based and time-based PM to 20 healthy young individuals. Analyses revealed that event- and time-based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event-based PM, probably reflecting target-checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time-based PM, which may reflect the involvement of time-estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event-based and time-based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. PMID- 24214216 TI - Continuous in vitro evolution of a ribozyme ligase: a model experiment for the evolution of a biomolecule. AB - Evolution is a defining criterion of life and is central to understanding biological systems. However, the timescale of evolutionary shifts in phenotype limits most classroom evolution experiments to simple probability simulations. In vitro directed evolution (IVDE) frequently serves as a model system for the study of Darwinian evolution but produces noticeable phenotypic shifts in a matter of hours. An IVDE demonstration lab would serve to both directly demonstrate how Darwinian selection can act on a pool of variants and introduce students to an essential method of modern molecular biology. To produce an IVDE demonstration lab, continuous IVDE of a T500 ribozyme ligase population has been paired with a fluorescent strand displacement reporter system to visualize the selection of improved catalytic function. A ribozyme population is taken through rounds of isothermal amplification dependent on the self-ligation of a T7 promoter. As the population is selectively enriched with better ligase activity, the strand displacement system allows for the monitoring of the population's ligation rate. The strand displacement reporter system permits the detection of ligated ribozyme. Once ligated with the T7 promoter, the 5' end of the ribozyme displaces paired fluorophore-quencher oligonucleotides, in turn, generating visible signal upon UV light excitation. As the ligation rate of the population increases, due to the selection for faster ligating species, the fluorescent signal develops more rapidly. The pairing of the continuous isothermal system with the fluorescent reporting scheme allows any user, provided with minimal materials, to model the continuous directed evolution of a biomolecule. PMID- 24214217 TI - A model-based approach to analyze the influence of UGT2B15 polymorphism driven pharmacokinetic differences on the pharmacodynamic response of the PPAR agonist sipoglitazar. AB - The pharmacokinetics of sipoglitazar, a peroxisome proliferator activated receptor agonist, are subject to high inter-individual variability resulting from a polymorphism of the UGT2B15 genotype. The aim of the current analysis was to apply a PK-PD model-based approach to evaluate the influence of UGT2B15 driven pharmacokinetic differences on the clinical response. Efficacy and safety of sipoglitazar compared to placebo were assessed in Type 2 Diabetes Mellitus patients in two Phase II randomized, double-blind studies (sipoglitazar once daily: 8, 16, 32, or 64 mg; sipoglitazar twice daily: 16 or 32 mg; rosiglitazone 8 mg once daily and placebo for 13 weeks; n = 780). Changes in fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels over time were described as a function of individual drug exposure using a simultaneous, cascading indirect response model structure. The effects on FPG and HbA1c could successfully be described for placebo, rosiglitazone, and sipoglitazar treated groups in all three UGT2B15 genotypes. Differences in drug effects between genotypes were fully explained by differences in drug exposure. The current PK-PD analysis confirms that UGT2B15 genotype is a major determinant for differences in FPG and HbA1c response to sipoglitazar treatment between Type 2 Diabetes mellitus patients, due to related differences in drug exposure. PMID- 24214218 TI - Overview of current standpoints in profiling of circulating tumor cells. AB - The goal of this review is summarizing current technologies developed as the in vitro prognostic/diagnostic systems that can rapidly separate and detect circulating tumor cells (CTCs) from cancer patient's blood (1-10 CTCs of 1 billion red blood cells) by labeled and non-labeled method. The review is focused on three major areas of CTC research (1) Summary of previous research on capturing of CTCs, (2) New development of the in vitro prognostic diagnosis system of cancer that is capable of rapid separation of CTCs, (3) Future direction on development of new technologies for CTC profiling. Current CTC researches have helped on identifying patients who may benefit from chemotherapy before treatment, patients who may benefit from continued chemotherapy, and leading to clinical development of CTC-guided chemotherapy strategies. We analyze the feasibility of clinical application of these current CTC research for the ultimate goal of increasing the survivability of cancer patient. The biomolecular assays of viable CTCs from cancer patient may elucidate the mechanism of metastasis and tumor initiating cells and also may have high impact on the development of personalized medicine to overcome the incurable diseases. PMID- 24214219 TI - Acute decompensated heart failure: evolving literature and implications for future practice. AB - Acute decompensated heart failure (ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain. PMID- 24214220 TI - Open access atmospheric pressure chemical ionization Mass spectrometry for routine sample analysis. AB - We report the introduction and use of an atmospheric pressure chemical ionization liquid chromatography-mass spectrometry instrument that has been designed specifically for use by the synthetic chemist on an open access, walk-in basis. This instrument has been configured with an easy-to-use sample log-in terminal that requires the user to provide only a sample identification number and a user name. Sample analysis takes approximately 4 min and provides the synthetic and medicinal chemist with rapid and reliable mass spectrometry analysis. Since installation of the system, it has analyzed an average of about 80 samples per day and has the capacity to run over 100 samples per day without the intervention of a specialist operator. This capability has eliminated the need for an operator to analyze routine samples and allows the mass spectroscopist more time to deal with problem solving. PMID- 24214221 TI - Putting mass spectrometry in the hands of the end user. AB - The ease of use of the newer liquid chromatography-mass spectrometry interfaces has made possible the automated acquisition of spectra from large batch queues of samples. This fact, combined with the realization that unit molecular mass determination was the only datum desired by a majority of drug discovery synthetic chemists, led us to develop open access mass spectrometry in the early 1990s. Open access spectrometers now scan over 100,000 samples per year from synthesis laboratories at Pfizer. Our experiences with this novel use of mass spectrometry in a large research facility are discussed and we detail some of the pitfalls we believe to be common to this approach. In addition, we offer some reflection on the cultural changes we have observed in our research environment since this experiment began. PMID- 24214222 TI - An inductively coupled plasma-time-of-flight mass spectrometer for elemental analysis. Part II: Direct current quadrupole lens system for improved performance. AB - An electrostatic quadrupole lens has been substituted for a cylindrical lens system used in the original inductively coupled plasma-time-of-flight mass spectrometer (ICP-TOFMS). With an improved vacuum system also installed, the cylindrical and quadrupole lenses are compared to each other and to the performance of the prototype ICP-TOFMS. The quadrupole lens requires no tradeoff between ion throughput and resolving power as was encountered with cylindrical lenses. The background noise in both ion-optical systems is within the same order of magnitude. Images of the ion beam formed by each ion-optical system have been obtained on a microchannel plate-phosphor screen. The quadrupole lens shows a higher ion-beam flux and produces a slitlike focus required in the orthogonal ICP TOFMS instrument. Signal-to-noise ratios in the ICP-TOFMS can be improved by using a technique called pulsed-ion injection that is particularly convenient with the quadrupole lens. In this technique, one quadrupole electrode is pulsed to prevent ions from entering the extraction zone except when an ion packet is to be extracted for mass analysis. This technique significantly reduces the noise over continuous ion injection. In the orthogonal ICP-TOFMS with pulsed-ion injection, 0.5 frnol of analyte could be detected in 1.4 ms with a proper data acquisition system. Overall, the combination of a quadrupole lens and pulsed-ion injection may provide detection limits for the ICP-TOFMS that are competitive with those of quadrupole inductively coupled plasma-mass spectrometry instruments. PMID- 24214223 TI - An inductively coupled plasma-time-of-flight mass spectrometer for elemental analysis. Part III: Analytical performance. AB - A time-of-flight mass spectrometer (TOFMS) was evaluated as a mass analyzer for inductively coupled plasma mass spectrometry (ICP-MS). The long-term drift of signals was in the range of 7-8% relative standard deviation, whereas the short term precision was between 5 and 20%, somewhat worse than is typically reported for commercial ICP-MS instruments (5%). However, precision can be improved considerably in the TOFMS by ratioing isotopic peaks or through internal standardization, a consequence of its ability to extract all measured ions simultaneously from the inductively coupled plasma. This feature was demonstrated by monitoring the (206)Pb/(208)Pb ratio with boxcar averagers. In this ratioing mode, precision was improved to approximately 0. 5%. Detection limits were measured with two alternative signal processing systems: (1) discriminator-gated integration and (2) integration of digitized spectra. Both methods improved the signal-to-noise ratio by a factor of from 10 to 100, although detection limits were still 1-2 orders of magnitude poorer for most elements than from the best commercial ICP-MS instruments. The dynamic range of the discriminator-gated integration system is over 4 orders of magnitude, but can be extended to 10(6) with planned increases in primary ion-beam current, which is currently 10-100 times lower than is found in other instruments. Virtually simultaneous multielement and multiisotope analysis is possible for masses from (7)Li to (209)Bi with minimal mass bias and detection limits on the 0. 4-2-ppb level. PMID- 24214224 TI - Comparison of charged derivatives for high energy collision-induced dissociation tandem mass spectrometry. AB - Fixed-charge derivatives have been used to direct the fragmentation pattern of high energy collision-induced dissociation tandem mass spectra for several years. It has been noted that a fixed-charge placed at a terminus of a peptide will simplify the pattern of fragment ions that are produced in collision-induced dissociation. Trimethylammoniumacetyl, dimethyloctylammoniumacetyl, and triphenylphosphoniumethyl derivatives have been cited in the literature for this purpose and many other structures are possible. This work compares the cited derivatives as well as some new structures. The criteria used include the ease of synthesis and purification of the derivatized peptide and the effects of the derivative on the peptide sequence fragment ion yield and ionization efficiency. The trimethylammoniumacetyl derivative is concluded to be the most practical for general use, whereas the dimethyloctylammoniumacetyl derivative is found to be desirable for use with hydrophilic peptides. PMID- 24214225 TI - False positives and the detection of cyclodextrin inclusion complexes by electrospray mass spectrometry. AB - The results of previous works that have claimed to detect cyclodextrin inclusion complexes via the "soft" ionization technique of electrospray ionization mass spectrometry are revisited. A more extensive study of cyclodextrin mixtures with amino acids and small peptides demonstrates that amino acid and peptide "complexes" are detected by electrospray mass spectrometry regardless of the presence (or not) of an aromatic moiety on the side chain. Amino acids that may be least likely to form hydrophobic inclusion complexes with cyclodextrin in solution generally show the most intense complex ions. The data suggest that these "complexes" are, in all likelihood, electrostatic adducts formed during the electrospray process. Systematic controls are suggested to ensure that "false positives" do not negate many of the claims concerning the detection of solution derived noncovalent compounds. PMID- 24214228 TI - The 11th Asilomar conference on mass spectrometry. PMID- 24214226 TI - Simplified application of quadrupolar excitation in Fourier transform ion cyclotron resonance mass spectrometry. AB - A new method for application of quadrupolar excitation to the trapped ion cell of a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer is presented. Quadrupolar excitation is conventionally applied to the two pairs of opposed electrodes that normally perform the excitation and detection functions in the FTICR experiment. Symmetry arguments and numerically calculated isopotential contours within the trapped ion cell lead to the conclusion that quadrupolar excitation can be applied to a single pair of opposed side electrodes. Examples of effective quadrupolar axialization via this method include a sevenfold signal-to-noise enhancement derived from 50 remeasurements of a single population of trapped bovine insulin ions and the selective isolation of a single charge state of horse heart myoglobin after an initial measurement that revealed the presence of 14 charge states. PMID- 24214230 TI - Correlation of cefpodoxime susceptibility with cephalothin and cefuroxime for urinary tract isolates. AB - This study attempted to determine whether cefuroxime was superior to cephalothin as a surrogate marker for cefpodoxime among urinary tract isolates. The MicroScan system (Siemens) was used to determine susceptibility for cephalothin and cefuroxime on consecutive cultures with a colony count of >=50 000 organisms. Simultaneously, an Etest (bioMerieux) for cefpodoxime was conducted. The cefpodoxime interpretation was compared to that of the other two agents, and the categorical agreement was calculated, defined as the percentage of identical susceptibility interpretations. Cefuroxime (83 %) had a significantly higher categorical agreement than cephalothin (63 %) among 300 isolates (P<0.01). The major error rate was 16 % for cephalothin and 3 % for cefuroxime. The very major error rate was 7 % for cephalothin and 14 % for cefuroxime among the 14 cefpodoxime-resistant isolates. For Escherichia coli, the major error rates were 15 % and 1 % for cephalothin and cefuroxime, respectively. Very major error rates were 9 % for both agents. Cefuroxime was a better predictor of cefpodoxime susceptibility than cephalothin, and appears to be the preferred surrogate agent for the MicroScan system, particularly for E. coli. PMID- 24214231 TI - Visible light mediated fast iterative RAFT synthesis of amino-based reactive copolymers in water at 20 degrees C. AB - The attempts to mediate iterative RAFT polymerization of ionic monomers through visible light irradiation in water at 20 degrees C is reported, in which complete conversions are attained in several tens of minutes and the propagation suspends/restarts immediately for multiple times on cycling irradiation. This technique suits the one-pot synthesis of NH2 /imidazole-based polymers with tuned structures from homo to random, block, random-block, and block-random-block, thus is robust and promising to control the sequence of the ionized water-soluble reactive copolymers. PMID- 24214233 TI - Survey of chemical constituents of Tehran's groundwater. AB - One hundred and forty wells throughout the City of Tehran and its environs were sampled to determine the chemical quality of the groundwater. Total alkalinity, pH, conductivity, total dissolved solids, hardness and detergent concentrations were determined as well as levels of bicarbonate, calcium, magnesium, sulphate, chloride, sodium, potassium, fluoride, iodide and nitrate. Generally, chemical pollution of the water supplies was low. There were, however, regional elevations in nitrate, chloride and fluoride. Elevated fluoride levels were primarily in the northern regions of the city while high nitrates and chlorides were found primariiy in industrial areas. The health implications of chemical constituents in drinking water are discussed. PMID- 24214232 TI - Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA. AB - BACKGROUND: The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments. AIM: The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon. METHODS: This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study-a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged>=18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21-28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150-300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints. Costs were estimated by examining the dosage of the study drug (paricalcitol or cinacalcet) and phosphate binders used by each participant during the trial. Nonparametric bootstrap analysis was used to examine the accuracy of the ICER point estimates. RESULTS: The percentages of patients achieving the treatment goal of a mean iPTH level between 150-300 pg/mL during weeks 21-28 of therapy were 56.9% in the paricalcitol group and 34.0% in the cinacalcet group (a difference of 23%, p=0.0235). Paricalcitol was also more effective for each of the secondary endpoints. When annualized, the total drug costs were US$10,153 in the paricalcitol group and US$15,967 in the cinacalcet group, a difference of US$5,814 (57.3%, p=0.0053). Because the paricalcitol-based treatment was less expensive and more effective, it was 'dominant', compared with cinacalcet, in this cost-effectiveness analyses. In our bootstrap analysis, 99.1% of bootstrap replicates for the ICER of the primary endpoint fell within the lower right quadrant of the cost-effectiveness plane-where paricalcitol is considered dominant. For all of the other endpoints, paricalcitol was dominant in 100% of replicates. CONCLUSION: On the basis of dosing and effectiveness data from US patients in the IMPACT SHPT study, we found that a regimen of intravenous paricalcitol was more cost effective than cinacalcet plus low-dose vitamin D in the management of iPTH in patients with SHPT requiring haemodialysis. PMID- 24214234 TI - A role forAmanita muscaria L. in the circulation of cadmium and vanadium in a non polluted woodland. AB - The sporophore of the fungusAmanita muscaria L. contains greatiy elevated levels of cadmium (29.9 MUg g(-1) dwt) and vanadium (344.9 MUg g(-1) dwt) in comparison with the soil in a birch woodland (total (HNO3-extractabie Cd 0.4 MUg g(-1) dwt, V 11.7 MUg g(-1) dwt). The significance of this remarkable concentration of normally rare and dispersed elements in terms of their circulation in the woodland has been investigated. Both elements are released from sporophore tissue in a form which can be taken up by a test plant (lettuce), cultivated in the woodland soil amended with different quantities of sporophore tissue, Cadmium levels in all plant tissues were elevated in comparison to the non-amended controls; only root vanadium levels responded to the amendment of the soil. The results are discussed in terms of their significance for the natural cycling of both elements. It is calculated that an abundant population of sporophores could circulate 1.4% of the total cadmium and 0.65% of the total vanadium pool found in the litter layer and 0-5 cm soil horizon in the sampled woodland over a period of 14 days (mean life span of a sporophore). PMID- 24214235 TI - The influence of house age on lead levels in dusts and soils in Brighton, England. AB - An earlier nationwide reconnaissance study had indicated that lead levels in housedusts in Brighton and Hove were high compared with the general mean for the United Kingdom (1110 MUg/g versus 507 MUug/g). A more rigorous study, with sample selection based on house age, has revealed a lower mean value of 705 MUg/g. Lead levels in 35 houses from the original study which were revisited had not changed significantly over the intervening 5 year period. The results suggest that the high mean value obtained previously was a reflection of the uneven age distribution in the sample population. The mean lead concentrations in soil and road dust samples, also obtained, were 404 and 794 MUg/g, respectively. Lead levels in ail three sample types (housedust, soil and road dust) were significantly correlated with each other and all showed a tendency to increase with increasing age of property. PMID- 24214236 TI - Radon from drinking water - evaluation of water-borne transfer into house air. AB - To determine the transfer of(222)Rn from domestic water into air, nine houses were measured for(222)Rnt, house volume, water use and air exchange by SF6 and radon. Measurements were done in Maine during April and May, 1986, when sealed up for the winter. Radon in water concentration ranged from 35,000 to 1,250,000 pCi/l. Air peaks of(222)Rn ranged from 13 to 200 pCi/l due to a water use burst experiment. Use of water filters was also examined by repeats with filters on and off. Water use ranged from 200 to 1922 litres/day. House volumes ranged from 380 to 999 m(3). Air exchange rates measured by SF6 was twice as large as air exchange rate measured by(222)Rn. PMID- 24214237 TI - Temporal trends in urban and rural blood lead concentrations. AB - A long term programme to assess the impact of reduced lead emissions in the UK has been established in central London and rural Suffolk. Blood lead concentrations of 5 and 6 year old children and their mothers both show an urban rural difference of about 1.5 MUg/dl, which is related to the urban-rural differences in air and dust lead concentrations between areas. PMID- 24214238 TI - Lead from dust and water as exposure sources for children. AB - Data from the Edinburgh Lead Study are used to estimate the respective contributions of water and dust lead to blood lead in 6-9 year old children. Both sources are significantly related to blood lead. An exposure of 100 MUg/l in kitchen cold water is estimated to be equivalent to 2700 MUg/g of lead in dust. In this population water is a more important source of lead than dust for the bulk of the population. PMID- 24214239 TI - Lead-based paint in dwellings: The potential for contamination of the home environment during renovation. AB - The quantity and particle size characteristics of lead in dust released during three different paint removal techniques was determined under controlled conditions and in situ in a dwelling. Air-lead and deposited dust-lead levels were highest after sanding but 'burning-off' and 'hot-air' removal methods also produced significant contamination. The importance of dust particle-size and lead is discussed in relation to the potential hazard to home renovators via inhalation and to children via the 'hand-to-mouth' route. PMID- 24214240 TI - Experimental boundaries of the quantum rotor induced polarization (QRIP) in liquid state NMR. AB - The Haupt-effect is a rather seldom used hyperpolarization method. It is based on the interdependence between nuclear spin states and rotational states of nearly free rotating methyl groups having C3 symmetry. A sudden change in temperature from 4.2 K to room temperature by fast dissolution yields considerably enhanced (13)C and (1)H resonance signals. This phenomenon is now termed quantum rotor induced polarization. More than 40 substances have been studied by this approach in order to identify them as polarizable by the 'Haupt-effect in the liquid state'. Influencing factors have been analyzed systematically. It could be concluded that substances having a high tunneling frequency, which is due to a small and narrow potential barrier, are most likely to feature quantum rotor induced polarization-enhanced signals. PMID- 24214241 TI - Impaired social processing in autism and its reflections in memory: a deeper view of encoding and retrieval processes. AB - Previous studies of memory in autism spectrum conditions (ASC) have consistently shown that persons with ASC have reduced memories for social information, relative to a spared memory for non-social facts. The current study aims to reproduce these findings, while examining the possible causes leading to this difference. Participants' memory for trait-words was tested after they had viewed the words in three study contexts: visuo-motor, letter-detection, and social judgment. While participants with ASC showed a levels-of-processing effect, such that their memory for words viewed in the social judgment context was greater than their memory for words viewed in the letter-detection context, their memory for socially-processed words was reduced relative to comparison participants. This interaction effect could not be explained by a speed/accuracy trade-off, nor could it be explained solely by differences in encoding. These results suggest that social memory deficits in ASC arise from difficulties both in orienting towards and encoding social content, as well as retaining and retrieving it. Implications for theory and clinical practice are discussed. PMID- 24214242 TI - Thalamic relay or cortico-thalamic processing? Old question, new answers. AB - What are the functions implemented by neurons in the sensory nuclei of the thalamus? It seems that this question has accompanied cortical and thalamic studies since their onset some 6 decades ago. Over the years, the simplistic, traditional view of thalamic neurons as mere relays of sensory information has given way to more sophisticated views, of which several alternative hypotheses have been proposed. This commentary briefly reviews the 2 current major hypotheses and shows how a new, pioneering experiment, published in Cerebral Cortex by Groh, Acsady and colleagues, discriminates between them. The commentary further elaborates on the thalamo-cortical processing suggested by the new findings, the general sensory-motor scheme to which these findings may be relevant, and the possible roles such thalamo-cortical processing may have in sensory-motor control. PMID- 24214244 TI - The impact of sustained engagement on cognitive function in older adults: the Synapse Project. AB - In the research reported here, we tested the hypothesis that sustained engagement in learning new skills that activated working memory, episodic memory, and reasoning over a period of 3 months would enhance cognitive function in older adults. In three conditions with high cognitive demands, participants learned to quilt, learned digital photography, or engaged in both activities for an average of 16.51 hr a week for 3 months. Results at posttest indicated that episodic memory was enhanced in these productive-engagement conditions relative to receptive-engagement conditions, in which participants either engaged in nonintellectual activities with a social group or performed low-demand cognitive tasks with no social contact. The findings suggest that sustained engagement in cognitively demanding, novel activities enhances memory function in older adulthood, but, somewhat surprisingly, we found limited cognitive benefits of sustained engagement in social activities. PMID- 24214246 TI - BVA appoints a new chief executive. PMID- 24214243 TI - Regulation of pyruvate metabolism in metabolic-related diseases. AB - Pyruvate is an obligatory intermediate in the oxidative disposal of glucose and a major precursor for the synthesis of glucose, glycerol, fatty acids, and non essential amino acids. Stringent control of the fate of pyruvate is critically important for cellular homeostasis. The regulatory mechanisms for its metabolism are therefore of great interest. Recent advances include the findings that (a) the mitochondrial pyruvate carrier is sensitive to inhibition by thiazolidinediones; (b) pyruvate dehydrogenase kinases induce the Warburg effect in many disease states; and (c) pyruvate carboxylase is an important determinate of the rates of gluconeogenesis in humans with type 2 diabetes. These enzymes are potential therapeutic targets for several diseases. PMID- 24214245 TI - Below-baseline suppression of competitors during interference resolution by younger but not older adults. AB - Resolving interference from competing memories is a critical factor in efficient memory retrieval, and several accounts of cognitive aging suggest that difficulty resolving interference may underlie memory deficits such as those seen in the elderly. Although many researchers have suggested that the ability to suppress competitors is a key factor in resolving interference, the evidence supporting this claim has been the subject of debate. Here, we present a new paradigm and results demonstrating that for younger adults, a single retrieval attempt is sufficient to suppress competitors to below-baseline levels of accessibility even though the competitors are never explicitly presented. The extent to which individual younger adults suppressed competitors predicted their performance on a memory span task. In a second experiment, older adults showed no evidence of suppression, which supports the theory that older adults' memory deficits are related to impaired suppression. PMID- 24214247 TI - Rabies confirmed in an imported kitten in France. PMID- 24214248 TI - Annual report indicates fall in veterinary antimicrobial sales in Europe in 2011. PMID- 24214251 TI - Agricultural collaboration to focus on sustainable food production. PMID- 24214252 TI - EFRACom announces food security inquiry. PMID- 24214253 TI - Proposals for halal assurance scheme open for consultation. PMID- 24214257 TI - Antimicrobial resistance: getting the message across. PMID- 24214258 TI - Thrombotic meningoencephalitis leads to sudden death in calves. PMID- 24214259 TI - The benefits of a strong hypothesis for retrospective research. PMID- 24214260 TI - Pathogen profiles in clinical mastitis cases. PMID- 24214261 TI - Providing assurance on food. PMID- 24214262 TI - Curbing livestock emissions. PMID- 24214269 TI - Postnatal development of auditory central evoked responses and thalamic cellular properties. AB - During development, the sense of hearing changes rapidly with age, especially around hearing onset. During this period, auditory structures are highly sensitive to alterations of the acoustic environment, such as hearing loss or background noise. This sensitivity includes auditory temporal processing, which is important for processing complex sounds, and for acquiring reading and language skills. Developmental changes can be observed at multiple levels of brain organization-from behavioral responses to cellular responses, and at every auditory nucleus. Neuronal properties and sound processing change dramatically in auditory cortex neurons after hearing onset. However, development of its primary source, the auditory thalamus, or medial geniculate body (MGB), has not been well studied over this critical time window. Furthermore, to understand how temporal processing develops, it is important to determine the relative maturation of temporal processing not only in the MGB, but also in its inputs. Cellular properties of rat MGB neurons were studied using in vitro whole-cell patch-clamp recordings, at ages postnatal day (P) 7-9; P15-17, and P22-32. Auditory evoked potentials were measured in P14-17 and P22-32 rats. MGB action potentials became about five times faster, and the ability to generate spike trains increased with age, particularly at frequencies of 50 Hz and higher. Evoked potential responses, including auditory brainstem responses (ABR), middle latency responses (MLR), and amplitude modulation following responses, showed increased amplitudes with age, and ABRs and MLRs additionally showed decreased latencies with age. Overall, temporal processing at subthalamic nuclei is concurrently maturing with MGB cellular properties. PMID- 24214270 TI - Relationship between metabolic rate in vitro and body mass in a marine teleost, porgy Pagrus major. AB - The rate of oxygen consumption of minced whole body was determined volumetrically, as an indication of metabolic rate in vitro (M in vitro ), at 20 degrees C in porgy Pagrus major ranging from 0.0002 g (just after hatch) to 2.9 g (67 days old) in body mass. A triphasic relationship was found between M in vitro of individual fish (MUl.min(-1)) and wet body mass W (g). During the prolarval stage accompanied with the transitional period to the postlarval stage (0.00020 0.00023 g, 0-6 days old), the mass-specific metabolic rate in vitro (M in vitro /W in MUl.g(-1).min(-1)) increased with age (D in days) as expressed by an equation M in vitro /W = 3.88 + 0.74/D. During the postlarval stage (0.00031 0.003 g, 8-22 days old), M in vitro /W remained almost constant, independent of body mass following an equation M in vitro /W = 5.24 W(-0.085). During the juvenile and adolescent stages (0.0047-2.9 g, 30-67 days old), M in vitro /W decreased with increasing body mass following an equation M in vitro /W = 1.66 W( 0.235). These results correspond with the triphasic relationship between metabolism in vivo and body mass observed in intact porgy of 0.0002-270 g (Oikawa et al. 1991). It is concluded, therefore, that the dependence of mass-specific metabolic rate on body size exists in vitro as well as in vivo, during the early stages in the porgy. Based on these results, factors controlling the metabolism size relationship are discussed. PMID- 24214268 TI - The Thellungiella salsuginea tonoplast aquaporin TsTIP1;2 functions in protection against multiple abiotic stresses. AB - Examination of aquaporin (AQP) membrane channels in extremophile plants may increase our understanding of plant tolerance to high salt, drought or other conditions. Here, we cloned a tonoplast AQP gene (TsTIP1;2) from the halophyte Thellungiella salsuginea and characterized its biological functions. TsTIP1;2 transcripts accumulate to high levels in several organs, increasing in response to multiple external stimuli. Ectopic overexpression of TsTIP1;2 in Arabidopsis significantly increased plant tolerance to drought, salt and oxidative stresses. TsTIP1;2 had water channel activity when expressed in Xenopus oocytes. TsTIP1;2 was also able to conduct H2O2 molecules into yeast cells in response to oxidative stress. TsTIP1;2 was not permeable to Na(+) in Xenopus oocytes, but it could facilitate the entry of Na(+) ions into plant cell vacuoles by an indirect process under high-salinity conditions. Collectively, these data showed that TsTIP1;2 could mediate the conduction of both H2O and H2O2 across membranes, and may act as a multifunctional contributor to survival of T. salsuginea in highly stressful habitats. PMID- 24214271 TI - Dietary rutin has limited synergistic effects on vitamin C nutrition of fingerling channel catfish (Ictalurus punctatus). AB - A study was conducted to determine the possible synergistic effects between dietary rutin (a bioflavonoid) and vitamin C, and to evaluate their antioxidant effects in fingerling channel catfish. Purified casein/gelatin diets containing two levels of rutin (0 and 1000 mg/kg diet) and three levels of L-ascorbic acid (0, 1500 and 3000 mg/kg diet) in a factorial arrangement were fed to fingerling channel catfish for 16 weeks. Fish fed the diets without supplemental vitamin C showed deformed spinal columns, external hemorrhages and fin erosion after 10 to 12 weeks. Also these fish had significantly (p < 0.05) depressed body weight gain, feed efficiency, hematocrit, hepatosomatic index (% liver weight), as well as reduced liver, fillet and plasma vitamin concentrations after 16 weeks. Liver, fillet and plasma vitamin C concentrations were correlated with dietary vitamin C levels. Forced oxidation of fillet samples significantly (p < 0.05) increased 2 thiobarbituric acid (TBA) values of fillets from fish fed diets without vitamin C and rutin. However, results from the present study indicated only limited synergistic effects of dietary rutin on vitamin C nutrition of channel catfish. PMID- 24214272 TI - Glucose-stimulated lipolysis in rainbow trout, Oncorhynchus mykiss, liver. AB - Rainbow trout, Oncorhynchus mykiss, were used to characterize further the influence of glucose on hepatic lipolysis. Liver was removed from fed fish, cut into 1 mm(3) pieces and incubated for up to 5 h in Hanks medium containing either 2 mM, 5.5 mM, 10 mM, or 25 mM glucose. Glucose-stimulated lipolysis was indicated by tissue triacylglycerol (TG) lipase activity and by medium concentrations of glycerol and fatty acids (FA). Triacylglycerol lipase activity in liver pieces incubated in the presence of higher concentrations (25 mM) of glucose was significantly higher than that in liver pieces incubated in lower concentrations (2 mM) of glucose, rising from 0.075 +/- 0.002 (mean +/- SEM) nmol FA released/h/mg protein to 0.092 +/- 0.004 units. Similarly, higher concentrations of glucose stimulated significantly more FA release and glycerol release from liver pieces than that stimulated by lower concentrations of glucose. Glycerol release from liver pieces incubated in the presence of 10 mM glucose and 25 mM glucose was ca. 2-fold to 2.8-fold, respectively, higher than that from liver pieces incubated in the presence of either 2 mM or 5.5 mM glucose. Fatty acid release from liver pieces incubated in the presence of 10 mM or 25 mM glucose was ca. 1.8-fold higher than that from liver pieces incubated in the presence of either 2 mM or 5.5 mM glucose. Notably, increased glycerol release was not accompanied by a parallel increase in FA. Fatty acid reesterification was more pronounced in liver pieces exposed to higher glucose (10 mM and 25 mM) than in liver pieces exposed to lower glucose (2 mM and 5.5 mM). (14)C-incorporation studies indicated that glucose serves as a carbon source for reesterified FA in trout liver. The route of reesterification appears to be from glucose to glycerophosphate to phosphatidic acid to diacylglycerol to TG. Increasing concentrations of glucose did not affect glycerol kinase activity, indicating that glucose-stimulated lipolysis was not accompanied by increased glycerol recycling within the liver. These results suggest that glucose stimulates fatty acid reesterification and directly enhances net lipolysis in trout liver incubated in vitro. PMID- 24214273 TI - Gluconeogenesis in trout (Oncorhynchus mykiss) white muscle: purification and characterization of fructose-1,6-bisphosphatase activity in vitro. AB - Studies of the enzyme fructose-1,6-bisphosphatase (FBPase) of rainbow trout (Oncorhynchus mykiss) have been undertaken in order to illuminate aspects of skeletal muscle gluconeogenesis in these animals. Maximal activities in crude homogenates of several organs suggest that the liver possesses the greatest FBPase activity on a unit g(-1) tissue basis but that the white muscle, owing to its bulk, contributes substantially to whole body FBPase activity. Studies of fructose-6-phosphate-1-kinase (PFK) and FBPase in crude homogenates of several organs suggests an important role for intracellular pH in regulating the relative carbon flux through the FBPase/PFK locus in vivo. Furthermore, a three-step purification scheme is described for trout white muscle FBPase by which a stable and homogeneous (by SDS PAGE) enzyme preparation (isoelectric point = 7.2; molecular weight = 37.6 kd) was obtained. Kinetic studies of the purified enzyme were undertaken at 20 degrees C under conditions reflective of "rest" and "exercise/recovery" intramuscular pH in vivo. Affinity for substrate (F-1,6-P2) was increased (Km = 6.88 versus 2.44 MUmol 1-(-1) as was enzyme activity when pH was lowered from 7.0 to 6.5. Various inhibitor metabolites are identified including F-2,6-P2 (mixed-type inhibitor, Ki = 0.201 MUmol 1(-1), pH 7.0) and AMP (non-competitive inhibitor, Ki = 0.438 MUmol 1(-1), pH 7.0). Inhibition by F-2,6 P2 was strongly alleviated by a reduction in pH from 7.0 to 6.5 (I50 increased from 0.14 to 0.32 MUmol 1(-1)). AMP on the other hand was a more potent inhibitor at pH 6.5 but this inhibition was totally reversed under conditions of citrate, NH4 (+) and AMP typical of muscle during recovery from exercise in vivo. In purified white muscle enzyme preparations, FBPase demonstrated maximal activity at pH 6.5 whereas the optimal pH of PFK was 7.0 or greater. Indeed, it appears from these in vitro data that regulation by metabolite levels as well as pH are required for net FBPase flux in vivo. It is concluded, therefore that trout white muscle FBPase demonstrates the potential to play an important enzymatic role in the control of intramuscular gluconeogenesis in these animals. The results are discussed in relation to present knowledge regarding the metabolic responses of trout white muscle to, and its subsequent recovery from, exhaustive exercise. PMID- 24214274 TI - Arachidonic acid metabolism in gill homogenate and isolated gill cells from rainbow trout, Oncorhynchus mykiss: the effect of osmolality, electrolytes and prolactin. AB - An assay method based on thin layer chromatography to study the arachidonic acid (AA) metabolism in gill tissues was optimized and the effect of osmotically different incubation mediums on AA metabolism was evaluated. Rainbow trout gill tissues metabolize AA into PGE2 in highest concentration followed by PGD2, PGF2alpha and 6-keto-PGF1alpha (the stable metabolite of PGI2) among the prostanoids tested. Approximately 40% of PGE2 is synthesized within the first minute of incubation and is directly dependent on the substrate concentration (AA). As in mammalian tissues, PGE2 synthesis in fish gills is inhibited by the cyclooxygenase inhibitor indomethacin. PGE2 synthesis in gill homogenate and isolated gill cells incubated in trout Ringer was 0.45 and 1.9 ng/mg protein, respectively, and increased to 8.9 and 4.3 ng/mg protein, respectively, when incubated in KPO4 buffer, due to a ten-fold increase in the free AA. The hydroxy acid synthesis of the gill homogenate was higher (13%), and that of the isolated gill cells incubated in KPO4 buffer was lower (44%) compared to gill homogenate and cells incubated in trout Ringer. Gill homogenate incubated in 50 mM phosphate buffer with increasing sodium or potassium concentrations (up to 250 mM) exhibited a concentration-dependent increase in PGE2 synthesis (220% and 72%, respectively). Prolactin stimulated the PGE2 synthesis up to 30% while PGD2, PGF2alpha and 6-keto-PGF1alpha synthesis was not affected. This effect of prolactin was maximal when PGE2 synthesis was estimated 30 minutes after prolactin addition and diminished after two hours. These results suggest that rainbow trout gills possess the ability to metabolize AA through the cyclooxygenase and lipoxygenase pathways. PGE2 synthesis may be under the influence of ion balance and prolactin availability, indicating the probable involvement of AA metabolites in the regulation of ion balances across the gill membrane. PMID- 24214275 TI - Effect of insulin in the diet on the growth of European eels (Anguilla anguilla L.). AB - The effect of oral administration of insulin, in various concentrations, on the growth of European eels (Anguilla anguilla L.) was studied. In order to determine whether the insulin penetrated through the stomach or gills to the blood system, 5 ml insulin, suspended in an 0.6% solution of NaCl, was inserted via the mouth of eels, and the insulin content in the blood measured by radioimmunoassay immediately, and at one and two hours after administration. A control group was given 0.6% NaCl alone. Significantly increased levels of insulin in the blood plasma were found in eels which received high insulin concentrations compared to the control group. Eels administered 20 ppm and 40 ppm insulin in the diet grew significantly faster than a control group fed a diet without insulin, and a group fed 5 ppm insulin. PMID- 24214276 TI - Histological changes in insulin-immunoreactive pancreatic beta-cells, and suppression of insulin secretion and somatotrope activity in brook trout (Salvelinus fontinalis) maintained on reduced food intake or exposed to acidic environment. AB - Immature brook trout (Salvelinus fontinalis) were randomly divided into a pH control, a pH and food control and an acid-stressed group. Fish in the first two groups were held at neutral pH and those in the last group were maintained at pH 4.2 for up to two months. The food supply to the pH and food control group was restricted to simulate the reduction in food intake demonstrated for acid stressed trout. Plasma insulin levels were significantly decreased from 5-20 ng/ml to 1-2 ng/ml and plasma cortisol levels were significantly increased from 5 10 ng/ml to as high as 70 ng/ml in the acid-stressed brook trout. Concomitantly, a significant decrease of 21-39% in the proportion (volume density) of insulin immunoreactive beta-cells was observed within the principal pancreatic islets. Somatic growth was stunted and ultrastructural morphometry revealed the suppression of somatotrope secretory activity in the acid-stressed fish. Restriction of food supply induced a smaller but still significant decrease in circulating levels of insulin which was however not accompanied by a reduction in insulin immunoreactive beta-cells. The rise in plasma cortisol levels was not significant, and the plasma levels of glucose and protein were unaffected. Nevertheless, somatotrope secretory activity was suppressed and somatic growth was stunted. This study demonstrates for the first time the complexity of the endocrine response to acid stress and that some of the response to acid stress can be attributed to the lowering of food intake. PMID- 24214277 TI - Temporal changes in plasma thyroid hormone, growth hormone and free fatty acid concentrations, and hepatic 5'-monodeiodinase activity, lipid and protein content during chronic fasting and re-feeding in rainbow trout (Oncorhynchus mykiss). AB - Temporal changes in growth, plasma thyroid hormone, cortisol, growth hormone (GH) and non-esterified fatty acid (NEFA) concentrations, hepatic T3 content and hepatic 5'-monodeiodinase activity were measured in rainbow trout (Oncorhynchus mykiss) subjected to a sustained fast for up to eight weeks, and during a four week re-feeding period. The purpose of the study was to examine aspects of the endocrine control of energy partitioning processes characteristic of short-term (acute; fasting) and long-term (chronic; starvation) food-deprivation states in fish, and to explore the role of the thyroid hormones, cortisol and GH in the energy repartitioning that takes place during an acute anabolic (re-feeding) state following chronic food deprivation.Differences in growth rate between fed and fasted groups were evident after two weeks, but significant weight loss by the fasted groups was not evident until between four and six weeks into the fast. Hepatosomatic indices (HSIs) were significantly reduced in the fasted fish within seven days, and as early as two days in one study; recovery of the HSI in fasted fish was evident within three days of re-feeding. Liver protein content (expressed as % wet weight) was consistently depressed in the fasted fish in only one of the three studies. Liver total lipid content (expressed as % wet weight) was depressed in the fasted fish within two days of food deprivation. Because of the rapid and sustained decrease in the HSI of fasted fish, the hepatic total protein and lipid reserves, when considered on a body weight basis, were markedly lowered within the first few days of the fast. Plasma GH concentrations exhibited a bi-modal pattern of change, with a transient fall in levels, followed by a sustained increase in fasted fish. The indicators of interrenal activity were suggestive of a depressed pituitary-interrenal axis in fasted animals; plasma cortisol levels were elevated to levels of fed animals within one day of re feeding. The indicators of thyroid hormone economy (plasma thyroid hormone levels, liver triiodothyronine content, hepatic 5'-monodeiodinase (MD) activity, thyroid epithelial cell height) were similarly indicative of a depressed pituitary-thyroid axis in fasted animals, with recovery to levels of the fed animals within one week. Despite the compensatory changes in accumulation of reserves (as indicated by a compensatory increase in HSI), there were no apparent compensatory changes in any of the endocrine parameters evident during the re feeding period. PMID- 24214278 TI - Freerunning circasemilunar spawning rhythm of Fundulus grandis and its temperature compensation. AB - Gulf killifish, Fundulus grandis, exhibit rhythmic reproductive activities that are synchronized with semilunar tidal fluctuations in their Gulf coast habitat. These cyclic activities, monitored through daily egg collections, persist in the laboratory for as long as four months with periods near the tidal period of 13.7 days. In nature, a specific semilunar spawning phase is maintained with respect to tidal cycles. However, in the laboratory, the phase may gradually advance or delay. These phase changes occur as a result of small differences between the periods of the spawning cycle and concurrent tidal cycle. Changes in the phase of the spawning cycle can be produced after several cycles by exposing fish to different temperatures (21 and 27 degrees C). However, the period of the spawning cycle changes only slightly with temperature. Q10 calculations produce a value not significantly different from 1.0, indicating nearly complete temperature compensation. These results provide evidence for an endogenous circasemilunar cycle that is temperature-compensated and freeruns in the laboratory. PMID- 24214279 TI - Highly efficient phase boundary biocatalysis with enzymogel nanoparticles. AB - The enzymogel nanoparticle made of a magnetic core and polymer brush shell demonstrates a novel type of remote controlled phase-boundary biocatalysis that involves remotely directed binding to and engulfing insoluble substrates, high mobility, and stability of the catalytic centers. The mobile enzymes reside in the polymer brush scaffold and shuttle between the enzymogel interior and surface of the engulfed substrate in the bioconversion process. Biocatalytic activity of the mobile enzymes is preserved in the enzymogel while the brush-like architecture favors the efficient interfacial interaction when the enzymogel spreads over the substrate and extends substantially the reaction area as compared with rigid particles. PMID- 24214280 TI - Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. AB - BACKGROUND: Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients with T2D. Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 randomised clinical trials that randomised 29 ,986 participants with T2D. We now report our updated review. OBJECTIVES: To assess the effects of targeted intensive glycaemic control compared with conventional glycaemic control in patients with T2D. SEARCH METHODS: Trials were obtained from searches of The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL (all until December 2012). SELECTION CRITERIA: We included randomised clinical trials that prespecified targets of intensive glycaemic control versus conventional glycaemic control targets in adults with T2D. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Dichotomous outcomes were assessed by risk ratios (RR) and 95% confidence intervals (CI). Health-related quality of life and costs of intervention were assessed with standardized mean differences (SMD) and 95% Cl. MAIN RESULTS: Twenty-eight trials with 34,912 T2D participants randomised 18,717 participants to intensive glycaemic control versus 16,195 participants to conventional glycaemic control. Only two trials had low risk of bias on all risk of bias domains assessed. The duration of the intervention ranged from three days to 12.5 years. The number of participants in the included trials ranged from 20 to 11,140. There were no statistically significant differences between targeting intensive versus conventional glycaemic control for all-cause mortality (RR 1.00, 95% CI 0.92 to 1.08; 34,325 participants, 24 trials) or cardiovascular mortality (RR 1.06, 95% CI 0.94 to 1.21; 34,177 participants, 22 trials). Trial sequential analysis showed that a 10% relative risk reduction could be refuted for all-cause mortality. Targeting intensive glycaemic control did not show a statistically significant effect on the risks of macrovascular complications as a composite outcome in the random-effects model, but decreased the risks in the fixed-effect model (random RR 0.91, 95% CI 0.82 to 1.02; and fixed RR 0.93, 95% CI 0.87 to 0.99; P = 0.02; 32,846 participants, 14 trials). Targeting intensive versus conventional glycaemic control seemed to reduce the risks of non-fatal myocardial infarction (RR 0.87, 95% CI 0.77 to 0.98; P = 0.02; 30,417 participants, 14 trials), amputation of a lower extremity (RR 0.65, 95% CI 0.45 to 0.94; P = 0.02; 11,200 participants, 11 trials), as well as the risk of developing a composite outcome of microvascular diseases (RR 0.88, 95% CI 0.82 to 0.95; P = 0.0008; 25,927 participants, 6 trials), nephropathy (RR 0.75, 95% CI 0.59 to 0.95; P = 0.02; 28,096 participants, 11 trials), retinopathy (RR 0.79, 95% CI 0.68 to 0.92; P = 0.002; 10,300 participants, 9 trials), and the risk of retinal photocoagulation (RR 0.77, 95% CI 0.61 to 0.97; P = 0.03; 11,212 participants, 8 trials). No statistically significant effect of targeting intensive glucose control could be shown on non-fatal stroke, cardiac revascularization, or peripheral revascularization. Trial sequential analyses did not confirm a reduction of the risk of non-fatal myocardial infarction but confirmed a 10% relative risk reduction in favour of intensive glycaemic control on the composite outcome of microvascular diseases. For the remaining microvascular outcomes, trial sequential analyses could not establish firm evidence for a 10% relative risk reduction. Targeting intensive glycaemic control significantly increased the risk of mild hypoglycaemia, but substantial heterogeneity was present; severe hypoglycaemia (RR 2.18, 95% CI 1.53 to 3.11; 28,794 participants, 12 trials); and serious adverse events (RR 1.06, 95% CI 1.02 to 1.10; P = 0.007; 24,280 participants, 11 trials). Trial sequential analysis for a 10% relative risk increase showed firm evidence for mild hypoglycaemia and serious adverse events and a 30% relative risk increase for severe hypoglycaemia when targeting intensive versus conventional glycaemic control. Overall health-related quality of life, as well as the mental and the physical components of health-related quality of life did not show any statistical significant differences. AUTHORS' CONCLUSIONS: Although we have been able to expand the number of participants by 16% in this update, we still find paucity of data on outcomes and the bias risk of the trials was mostly considered high. Targeting intensive glycaemic control compared with conventional glycaemic control did not show significant differences for all-cause mortality and cardiovascular mortality. Targeting intensive glycaemic control seemed to reduce the risk of microvascular complications, if we disregard the risks of bias, but increases the risk of hypoglycaemia and serious adverse events. PMID- 24214281 TI - Rebanding for slippage after gastric banding: should we do it? AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a commonly performed bariatric procedure. LAGB is frequently complicated by slippage. Possible treatment for slippage is rebanding, but long-term effects are unknown. The aim of this study was to investigate whether rebanding after gastric band slippage is associated with weight loss failure. METHODS: This was a post hoc analysis of a prospectively collected database of 627 consecutive LAGB patients. Rebanding for slippage was performed in 81 patients. The effect of rebanding on weight loss was evaluated by three analyses: (1) in 81 rebanded patients, weight loss was compared before and after rebanding, separately for patients in whom primary LAGB was successful or unsuccessful; (2) 81 rebanded patients were matched to 81 patients without slippage for prognostic variables and compared for weight loss after rebanding; (3) multivariate logistic regression was performed whether rebanding was independently associated with weight loss failure. RESULTS: The chance of a fair result of rebanding for patients following primary successful (n = 34) and unsuccessful LAGB (n = 22) was 62 and 27 % after median follow-up of 113 and 97 months, respectively. There was no difference in weight loss failure between 81 rebanded patients and 81 matched patients: 54 vs 59 % (P = 0.43). In multivariate analysis, rebanding was not significantly associated with weight loss failure: adjusted odds ratio 1.42; 95 % confidence interval 0.85 2.38; P = 0.18. CONCLUSION: In general, rebanding after LAGB has no negative effect on weight loss. However, patients in whom LAGB was unsuccessful prior to rebanding have poor long-term weight loss results. PMID- 24214282 TI - Pre-operative dietary restriction for patients undergoing bariatric surgery in the UK: observational study of current practice and dietary effects. AB - BACKGROUND: Bariatric surgery is effective at achieving weight loss in the severely obese, with the majority of procedures performed laparoscopically. A short-term pre-operative energy restrictive diet is widely adopted to enable surgery by reducing liver size and improving liver flexibility. However, the dietary approach is not standardised. This observational study reports on pre operative restrictive diets in use across bariatric services in the UK. METHODS: Between September and November 2012, information was collected from bariatric services on current or past pre-operative diets, and any research providing evidence for the use or modification of their diets. RESULTS: Around one third of bariatric services (28) in the UK responded, with a total of 49 diets in current use. Types of diet include low energy, low carbohydrate and liquid, with 59 % offering low energy/low carbohydrate food-based, 21 % milk/yoghurt, 18 % meal replacement (liquid) and 2 % clear liquid. Diet duration varies between 7 and 42 days. Limited anecdotal evidence was provided by services evaluating the pre operative diet, and its alternative approaches, with dietary choice primarily clinician-led. CONCLUSIONS: This study has highlighted variability and lack of consensus in the form of pre-bariatric surgery diet used across different centres. Further research comparing outcomes for alternative diets would support best practice in the future. PMID- 24214283 TI - Efficacy of a laparoscopic gastric restrictive device in an obese canine model. AB - BACKGROUND: Bariatric surgery using laparoscopic techniques is the most effective treatment for morbid obesity. The objective of the study is to assess the safety and efficacy of a novel laparoscopic reversible gastric restrictive (RGR) device in a group of obese dogs. An implant was also performed in a cadaver to assess implant feasibility in a human. METHODS: Four obese mongrel dogs were subjected to RGR implantation for 3 months followed by recovery for an additional 6 weeks after device removal. Food intake, body weight, radiographic barium imaging, and gastric endoscopy were used to monitor RGR performance before implant, after implant, and implant removal. An additional RGR laparoscopic implantation procedure was performed in a human cadaver. RESULTS: The implanted obese dogs exhibited a significant decrease in food intake and body weight over 3 months with the RGR device. The reduction of food intake was sustained at an average of 46 % after implant and the excess weight loss reached an average of 75 % at the end of 12 weeks with recovery to approximately 78 % of baseline after 6 weeks of implant removal. Barium imaging and gastric endoscopy both confirmed passage for food through the restrictive device channel in the stomach. The RGR device was successfully implanted laparoscopically on the cadaver stomach in less than an hour. CONCLUSIONS: The RGR device is laparoscopically deliverable and removable with effective and sustainable weight loss over a 12-week period in an obese dog model. The implant is also technically feasible in man. PMID- 24214284 TI - Shortening of the QT interval is observed soon after sleeve gastrectomy in morbidly obese patients. AB - BACKGROUND: Morbidly obese patients have an increased risk of sudden cardiac death. It is well known that obesity prolongs the QT interval, which in turn may cause ventricular arrhythmia and sudden cardiac death. The objective of this study was to establish whether sleeve gastrectomy shortens the QT interval. METHODS: Twenty-eight consecutive patients underwent sleeve gastrectomy at our institution between September 2010 and March 2011 and were included in the study. The indications for bariatric surgery were in accordance with French national guidelines. For each patient, an electrocardiogram was recorded before and then 3 months after surgery. The corrected QT (QTc) was determined independently by two physicians. RESULTS: The mean body mass index was 45.27 +/- 6.09 kg/m(2) before surgery and 38.32 +/- 5.19 kg/m(2) 3 months after surgery. The mean weight loss over this period was 20.71 +/- 7.57 kg. The QTc interval was 427 +/- 18.6 ms (415.7 +/- 12.06 in men and 428.4 +/- 18.96 in women) prior to surgery and was significantly lower 3 months after surgery (398.6 +/- 15.5 ms overall, 391.3 +/- 7.63 in men, and 399.6 +/- 16.02 in women). The QTc interval decreased in all individual patients (by an average of 28.5 +/- 15.6 ms overall, 24.3 +/- 8.38 in men, and 29 +/- 16.23 in women). Weight loss and decreased QTc interval were not significantly correlated (p = 0.88). CONCLUSION: Sleeve gastrectomy in morbidly obese patients was associated with a significantly lower QTc interval 3 months after surgery. These findings imply that bariatric surgery might reduce the risk of sudden cardiac death in this patient population. PMID- 24214285 TI - Mechanism and clinical evidence of lipocalin-2 and adipocyte fatty acid-binding protein linking obesity and atherosclerosis. AB - Obesity is considered to be a chronic inflammatory state in which the dysfunction of adipose tissue plays a central role. The adipokines, which are cytokines secreted by adipose tissue, are key links between obesity and related diseases such as metabolic syndrome and atherosclerosis. LCN2 and A-FABP, both of which are major adipokines predominantly produced in adipose tissue, have recently been shown to be pivotal modulators of vascular function. However, different adipokines modulate the development of atherosclerosis in distinctive manners, which are partly attributable to their unique regulatory mechanisms and functions. This review highlights recent advances in the understanding of the role of two adipokines in mediating chronic inflammation and the pathogenesis of atherosclerosis. PMID- 24214286 TI - Transient epileptic amnesia: clinical report of a cohort of patients. AB - Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients. PMID- 24214287 TI - A promising method to distinguish vascular dementia from Alzheimer's disease with standardized low-resolution brain electromagnetic tomography and quantitative EEG. AB - In clinical settings, it is difficult to distinguish Alzheimer's disease (AD) from vascular dementia (VD). The present study summarizes a clinical method to distinguish VD and AD at the early stage of the diseases. This study evaluated the possibility of differentiating 25 VD, 25 AD, and 25 healthy individuals (control, CN) by means of power spectral analysis and standardized low-resolution brain electromagnetic tomography (sLORETA) within alpha 1, alpha 2, beta 1, beta 2, delta, and theta frequency bands. Electroencephalogram (EEG) spectral analysis and sLORETA indicated that higher diffuse delta/theta and lower central/ posterior fast frequency bands were present in AD compared with CN. VD showed diffuse increased theta power compared with CN and lower delta than AD. AD also presented diffuse higher theta on spectral analysis and decreased alpha 2 and beta 1 values in central/temporal regions by sLORETA. Mini Mental State Examination (MMSE) scores were significantly associated with frontal alpha 1 sLORETA solutions (r = 0.91616, P < .001) and relative power (r = 0.87322, P < .01) in AD, but no correlations were found in VD. In conclusion, EEG spectral and sLORETA together could be a tool to distinguish the different EEG rhythmic activities in AD and VD. PMID- 24214288 TI - Triptycene-based microporous polymer with pending tetrazole moieties for CO2 capture application. AB - Triptycene-based micorporous polymer is functionalized with CO2 -philic tetrazole moieties via ZnCl2 -catalyzed post-polymerization. Gas adsorption experiments indicate that it possesses high CO2 uptake capacity, reaching 134 cm(3) g(-1) (26.5 wt%) at 1.0 bar and 273 K, along with high selectivity towards CO2 over N2 and CH4 . The porous polymeric networks present the promising potentials as efficient adsorbents in clean energy applications. PMID- 24214289 TI - Economic evaluation of the impact of medication errors reported by U.S. clinical pharmacists. AB - OBJECTIVE: Medication errors defined as "any preventable event that may cause or lead to inappropriate medication use or patient harm" have been highlighted as a top national priority in a report issued by the Institute of Medicine. However, little information is available on precise costs of medication errors. This study estimated the cost of medication errors reported by clinical pharmacists using a modified societal perspective. METHODS: Information on 779 medication errors was collected in the Medication Error Detection, Amelioration and Prevention (MEDAP) study that documented medication errors observed by clinical pharmacists during a consecutive 14-day period. The rate of medication errors, outcomes (number of errors resulting in temporary/permanent patient harm, prolonged hospitalization, or life-sustaining therapy), and interventions (communication, medication changes, patient monitoring, and treatment referrals) were collected. A decision model was developed to estimate the economic impact of medication errors reported by clinical pharmacists. Event probabilities were derived from MEDAP data. Direct costs were obtained through reviews of the literature, hospital charge data, and Medicare and Medicaid reimbursement. One-way and Monte Carlo sensitivity analyses were used to explore uncertainty in the values. RESULTS: In the base case, the mean expected cost of a medication error was $88.57. In the Monte Carlo simulation, the mean cost was $89.35 (+/- $30.17 SD). One-way sensitivity analysis revealed that changes in the probability of medication errors causing hospitalization and the cost of hospitalization had the greatest variability on the outcome ($50.44-$155.81 [probability of hospitalization], $32.59-$136.40 [cost of hospitalization]). CONCLUSIONS: Medication errors are costly to the health care system. A better understanding of medication error costs may be used to justify initiatives to reduce the risk and inefficiency associated with these errors. PMID- 24214291 TI - PKG in honey bees: spatial expression, Amfor gene expression, sucrose responsiveness, and division of labor. AB - Division of labor is a hallmark of social insects. In honey bees, division of labor involves transition of female workers from one task to the next. The most distinct tasks are nursing (providing food for the brood) and foraging (collecting pollen and nectar). The brain mechanisms regulating this form of behavioral plasticity have largely remained elusive. Recently, it was suggested that division of labor is based on nutrition-associated signaling pathways. One highly conserved gene associated with food-related behavior across species is the foraging gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Our analysis of this gene reveals the presence of alternative splicing in the honey bee. One isoform is expressed in the brain. Expression of this isoform is most pronounced in the mushroom bodies, the subesophageal ganglion, and the corpora allata. Division of labor and sucrose responsiveness in honey bees correlate significantly with foraging gene expression in distinct brain regions. Activating PKG selectively increases sucrose responsiveness in nurse bees to the level of foragers, whereas the same treatment does not affect responsiveness to light. These findings demonstrate a direct link between PKG signaling in distinct brain areas and division of labor. Furthermore, they demonstrate that the difference in sensory responsiveness between nurse bees and foragers can be compensated for by activating PKG. Our findings on the function of PKG in regulating specific sensory responsiveness and social organization offer valuable indications for the function of the cGMP/PKG pathway in many other insects and vertebrates. PMID- 24214292 TI - Darwin and the puzzle of primogeniture : An essay on biases in parental investment after death. AB - A historical survey of the inheritance practices of farming families in North America and elsewhere indicates that resource allocations among children differed through time and space with regard to sex bias and equality. Tensions between provisioning all children and maintaining a productive economic entity (the farm) were resolved in various ways, depending on population pressures, the family's relative resource level, and the number and sex of children.Against a backdrop of generalized son preference, parents responded to ecological circumstances by investing in offspring differentially within and between the sexes. Vesting the preponderance of family resources in one heir increased the likelihood of at least one line surviving across several generations, whereas varying degrees of parental investment in emigrating sons or out-marrying daughters might yield boom or bust harvests of grandchildren according to circumstances in more remote locales. Primogeniture (eldest son as primary heir) allowed early identification of heirs and appropriate socialization, as well as more time for parents to contribute to the heir's reproductive success. Son bias and unigeniture decreased as numbers of children per family declined, as land became less critical to economic success, and as legal changes improved the resource-holding potential of females. We suggest that changing ecological conditions affected parental decisions regarding resource allocation among children at least as much as did changing ideologies of parent-child relations. PMID- 24214290 TI - Concise review: Leukemia stem cells in personalized medicine. AB - Despite increased comprehension of acute myelogenous leukemia (AML) pathogenesis, current treatment strategies have done little to improve upon standard induction chemotherapy to induce long-term remissions. Since the identification of the leukemic stem cell, efforts have been placed on identifying therapeutically actionable pathways that distinguish this increasingly important cellular compartment. With the advent of increased genome sequencing efforts and phenotypic characterization, opportunities for personalized treatment strategies are rapidly emerging. In this review, we highlight recent advances in the understanding of leukemic stem cell biology and their potential for translation into clinically relevant therapeutics. NF-kappa B activation, Bcl-2 expression, oxidative and metabolic state, and epigenetic modifications all bear their own clinical implications. With advancements in genetic, epigenetic, and metabolic profiling, personalized strategies may be feasible in the near future to improve outcomes for AML patients. PMID- 24214293 TI - The evolution of sexuality in chimpanzees and bonobos. AB - The evolution of nonconceptive sexuality in bonobos and chimpanzees is discussed from a functional perspective. Bonobos and chimpanzees have three functions of sexual activity in common (paternity confusion, practice sex, and exchange for favors), but only bonobos use sex purely for communication about social relationships. Bonobo hypersexuality appears closely linked to the evolution of female-female alliances. I suggest that these alliances were made possible by relaxed feeding competition, that they were favored through their effect on reducing sexual coercion, and that they are ultimately responsible for the relaxed social conditions that allowed the evolution of "communication sex." PMID- 24214294 TI - Cultivating male allies : A focus on primate females, includingHomo sapiens. AB - Females make large investments in their children and compete among themselves to establish and maintain privileged relationships with male allies who demonstrate both an ability and a willingness to provide fitness-enhancing advantages. Various "strategies" and their more numerous, associated "tactics" are utilized in the competition. Alleged strategies include using sexuality, producing offspring, assisting the male in his own intrasexual contests, and harassing female competitors. The strategies in question are documented in multiple primate species, including humans living in various times and places. Some variables are discussed that influence the degree to which human females rely upon them. PMID- 24214295 TI - Objective approach for analysis of noise source characteristics and acoustic conditions in noisy computerized embroidery workrooms. AB - It is highly important to analyze the acoustic properties of workrooms in order to identify best noise control measures from the standpoint of noise exposure limits. Due to the fact that sound pressure is dependent upon environments, it cannot be a suitable parameter for determining the share of workroom acoustic characteristics in producing noise pollution. This paper aims to empirically analyze noise source characteristics and acoustic properties of noisy embroidery workrooms based on special parameters. In this regard, reverberation time as the special room acoustic parameter in 30 workrooms was measured based on ISO 3382-2. Sound power quantity of embroidery machines was also determined based on ISO 9614 3. Multiple linear regression was employed for predicting reverberation time based on acoustic features of the workrooms using MATLAB software. The results showed that the measured reverberation times in most of the workrooms were approximately within the ranges recommended by ISO 11690-1. Similarity between reverberation time values calculated by the Sabine formula and measured values was relatively poor (R (2) = 0.39). This can be due to the inaccurate estimation of the acoustic influence of furniture and formula preconditions. Therefore, this value cannot be considered representative of an actual acoustic room. However, the prediction performance of the regression method with root mean square error (RMSE) = 0.23 s and R (2) = 0.69 is relatively acceptable. Because the sound power of the embroidery machines was relatively high, these sources get the highest priority when it comes to applying noise controls. Finally, an objective approach for the determination of the share of workroom acoustic characteristics in producing noise could facilitate the identification of cost-effective noise controls. PMID- 24214296 TI - Accessing indoor fungal contamination using conventional and molecular methods in Portuguese poultries. AB - Epidemiological studies showed increased prevalence of respiratory symptoms and adverse changes in pulmonary function parameters in poultry workers, corroborating the increased exposure to risk factors, such as fungal load and their metabolites. This study aimed to determine the occupational exposure threat due to fungal contamination caused by the toxigenic isolates belonging to the complex of the species of Aspergillus flavus and also isolates from Aspergillus fumigatus species complex. The study was carried out in seven Portuguese poultries, using cultural and molecular methodologies. For conventional/cultural methods, air, surfaces, and litter samples were collected by impaction method using the Millipore Air Sampler. For the molecular analysis, air samples were collected by impinger method using the Coriolis MU air sampler. After DNA extraction, samples were analyzed by real-time PCR using specific primers and probes for toxigenic strains of the Aspergillus flavus complex and for detection of isolates from Aspergillus fumigatus complex. Through conventional methods, and among the Aspergillus genus, different prevalences were detected regarding the presence of Aspergillus flavus and Aspergillus fumigatus species complexes, namely: 74.5 versus 1.0 % in the air samples, 24.0 versus 16.0 % in the surfaces, 0 versus 32.6 % in new litter, and 9.9 versus 15.9 % in used litter. Through molecular biology, we were able to detect the presence of aflatoxigenic strains in pavilions in which Aspergillus flavus did not grow in culture. Aspergillus fumigatus was only found in one indoor air sample by conventional methods. Using molecular methodologies, however, Aspergillus fumigatus complex was detected in seven indoor samples from three different poultry units. The characterization of fungal contamination caused by Aspergillus flavus and Aspergillus fumigatus raises the concern of occupational threat not only due to the detected fungal load but also because of the toxigenic potential of these species. PMID- 24214297 TI - Tolerance values of benthic macroinvertebrates for stream biomonitoring: assessment of assumptions underlying scoring systems worldwide. AB - Tolerance values (TVs) based on benthic macroinvertebrates are one of the most widely used tools for monitoring the biological impacts of water pollution, particularly in streams and rivers. We compiled TVs of benthic macroinvertebrates from 29 regions around the world to test 11 basic assumptions about pollution tolerance, that: (1) Arthropoda are < tolerant than non-Arthropoda; (2) Insecta < non-Insecta; (3) non-Oligochaeta < Oligochaeta; (4) other macroinvertebrates < Oligochaeta + Chironomidae; (5) other macroinvertebrate taxa < Isopoda + Gastropoda + Hirudinea; (6) Ephemeroptera + Plecoptera + Trichoptera (EPT) < Odonata + Coleoptera + Heteroptera (OCH); (7) EPT < non-EPT insects; (8) Diptera < Insecta; (9) Bivalvia < Gastropoda; (10) Baetidae < other Ephemeroptera; and (11) Hydropsychidae < other Trichoptera. We found that the first eight of these 11 assumptions were supported despite regional variability. In addition, we examined the effect of Best Professional Judgment (BPJ) and non-independence of TVs among countries by performing all analyses using subsets of the original dataset. These subsets included a group based on those systems using TVs that were derived from techniques other than BPJ, and groups based on methods used for TV assignment. The results obtained from these subsets and the entire dataset are similar. We also made seven a priori hypotheses about the regional similarity of TVs based on geography. Only one of these was supported. Development of TVs and the reporting of how they are assigned need to be more rigorous and be better described. PMID- 24214298 TI - Dissociation of tetrameric ions of noncovalent streptavidin complexes formed by electrospray ionization. AB - The noncovalent tetrameric association of the protein streptavidin formed by electrospray ionization (ESI) mass spectrometry has been observed intact and dissociated in the gas phase. An extended mass-to-charge ratio range quadrupole mass spectrometer was employed to examine the effects of harsher conditions in the ESI atmosphere-vacuum interface region on the streptavidin tetramer. Thermally induced dissociation caused the mass spectra to exhibit a series of complementary monomer and trimer ions that correspond to decomposition of the tetrameric species. Similar results were obtained with tandem mass spectrometric experiments on a Fourier transform ion cyclotron resonance mass spectrometer by application of sustained off-resonance irradiation (SORI) on a selected tetrameric charge state. The technique of single-frequency quadrupole excitation was used to accomplish selected-ion accumulation of the 14 + charge state of the tetramer during ion injection. Subsequent low energy SORI combined with broadband quadrupole cooling produced the 7 + monomer and 7 + trimer species, as well as the 6 + monomer and 8 + trimer complementary ions. The observed asymmetric breakup of the tetramer is qualitatively explained by using physical models. PMID- 24214299 TI - The bimolecular hydrogen-deuterium exchange behavior of protonated alkyl dipeptides in the gas phase. AB - As part of an ongoing characterization of the intrinsic chemical properties of peptides, thermal hydrogen-deuterium exchange has been studied for a series of fast-atom-bombardment-generated protonated alkyldipeptides and related model compounds in the reaction with D2O, CH3OD, and ND3 in a Fourier transform ion cyclotron resonance mass spectrometer. Despite the very large basicity difference between the dipeptides and the D2O and CH3OD exchange reagents, efficient exchange of all active hydrogen atoms occurs. From the kinetic data it appears that exchange of the amino, amide, and hydroxyl hydrogens proceeds with different efficiencies, which implies that the proton in thermal protonated dipeptides is immobile. The selectivity of the exchange at the different basic sites is governed by the nature of both the dipeptide and the exchange reagent. The results indicate that reversible proton transfer in the reaction complexes, which effectuates the deuterium incorporation, is assisted by formation of multiple hydrogen bonds between the reagents. Exchange is considered to proceed via the intermediacy of different competing intermediate complexes, each of which specifically leads to deuterium incorporation at different basic sites. The relative stabilization of the competing intermediate complexes can be related to the relative efficiencies of deuterium incorporation at different basic sites in the dipeptide. For all protonated dipeptides studied, the exchange in the reaction with ND3 proceeds with unit efficiency, whereas all active hydrogen atoms are exchanged equally efficiently. Evidently specific multiple hydrogen bond formations are far less important in the reversible proton transfers with the relatively basic ammonia, which allows effective randomization of all active hydrogen atoms in the reaction complexes. PMID- 24214300 TI - Fingerprinting proteins coupled with polymers by mass spectrometry: Investigation of polyethylene glycol-conjugated superoxide dismutase. AB - Matrix-assisted laser desorption-ionization (MALDI) mass spectrometry was investigated as a method for the rapid determination of the extent of polymer coupling in polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD). PEG conjugated SOD, an antioxidant with an extended in vivo circulation lifetime compared to that of superoxide dismutase, is being evaluated as an effective therapeutic agent for the treatment of injuries and arthritis. The mass spectra of a standard batch of PEG-conjugated bovine SOD showed the presence of identifiable and well resolved peaks that correspond to 0-7 PEG molecules attached to bovine SOD. The area of each of the peaks provides a determination of the amount of PEG-conjugated SOD with a given number of bound PEG groups. SOD is a noncovalent dimer of two identical subunits that dissociates in MALDI. The information obtained in the mass spectra thus corresponds to a monomer of SOD. Each SOD monomer contains 10 lysines, which are the sites of PEG-conjugation. Multiple MALDI determinations of two batches of samples indicated good reproducibility for routine determination of the extent of polymer content. The amount of PEG-conjugated SOD that contained a given number of PEG molecules, determined by MALDI, was compared with the value deduced from the amount of PEG conjugation at each attachment site measured by a peptide mapping method. Agreement between the data obtained in the two techniques (MALDI and peptide mapping) indicates that MALDI may be used to obtain quantitative information on PEG-conjugated SOD to determine the amounts of PEG-conjugated protein each with a different number of PEG groups attached. Measurement of several batches of samples stored at a higher temperature showed a lower extent of PEG-conjugation in PEG-conjugated SOD. This reduction in the PEG content resulted from the PEG deconjugation of PEG-conjugated SOD at a higher temperature. Thus, MALDI can be used to examine the stability of PEG-conjugated SOD. The high sensitivity, relatively straightforward data interpretation, speed of analyses, and good reproducibility in measurements make this technique a useful analytical tool for fingerprinting PEG-conjugated SOD as well as potentially other polymer-conjugated proteins. PMID- 24214301 TI - Fragmentation of protonated O,O-dimethyl O-aryl phosphorothionates in tandem mass spectral analysis. AB - A study was carried out on the fragmentation of 12 protonated O,O-dimethyl O-aryl phosphorothionates by tandem quadrupole mass spectrometry. Some of the studied compounds are used in agriculture as pesticides. Energy-resolved and pressure resolved experiments were performed on the [M + H](+) ions to investigate the dissociation behavior of the ions with various amounts of internal energy. On collisionally activated dissociation, the [M + H](+) ions decompose to yield the [M + H - CH3OH](+), (CH3O)2PS(+) (m/z 125), and (CH3O)2PO(+) (m/z 109) ions as major fragments. The ions [M + H - CH3OH](+) and (CH3O)2PS(+) probably arise from the [M + H](+) ions of the O,O-dimethyl O-aryl phosphorothionates with the proton on the sulfur or on the oxygen of the phenoxy group. The origin of the hydroxy proton of the methanol fragment was in many cases, surprisingly, the phenyl group and not the reagent gas. This was confirmed by using deuterated isobutane, C4D10, as reagent gas in Cl. The fragment ions (CH3O)2PO(+) and [ZPhS](+) are the results of thiono-thiolo rearrangement reaction. The precursor ion for the ion (CH3O)2PO(+) arises from most compounds upon chemical ionization, whereas the precursor ion for the ion [ZPhS](+) arises only from a few compounds upon chemical ionization. The observed fragments imply that several sites carry the extra proton and that these sites get the proton usually upon ionization. The stability order and some characteristics of three protomers of O,O-dimethyl O phenyl phosphorothionate were investigated by ab initio calculations at the RHF/3 21G* level of theory. PMID- 24214302 TI - Fragmentation of conjugate bases of esters derived from multifunctional alcohols including triacylglycerols. AB - Enolate anions of esters from 1,2 and 1,3 diols undergo an internal nucleophilic substitution reaction that produces a beta-ketoester and an alkoxide ion within the molecular species. These intermediate ions undergo two competitive fragmentation pathways. The first pathway corresponds to a second nucleophilic substitution of the ketoester by the alkoxide that yields a neutral cyclic ether and the beta-ketoacid carboxylate. The latter then loses carbon dioxide and produces the enolate anion of the corresponding ketone. The second proposed pathway is stepwise: it starts with a proton transfer from the methylene group between the two carbonyls to the alkoxide anion that produces an alcohol and the enolate ion of the beta-ketoester inside the molecular species. The latter undergoes cleavage of the ester bond induced by the negative charge to yield an ion-dipole complex composed of a neutral acylketene and an alkoxide ion. The direct dissociation of this ion-dipole complex competes with an internal proton exchange to yield a new complex that consists of an alcohol molecule and the anion of the acylketene, which can also dissociate. The fragmentation pathway that leads to the ketone enolate is sensitive to the relative positions (1,2 or 1,3) of the esters on the molecular backbone. This position-sensitive reaction is useful for the assignment of the primary and secondary positions in triacylglycerols, even in mixtures, as shown by some examples. PMID- 24214303 TI - Optimization of the Hewlett-Packard particle-beam liquid chromatography-mass spectrometry interface by statistical experimental design. AB - Optimization of both sensitivity and ionization softness for the Hewlett-Packard particle-beam liquid chromatography-mass spectrometry interface has been achieved by using a statistical experimental design with response surface modeling. Conditions for both optimized sensitivity and ionization softness were found to occur at 55-lb/in.(2) nebulizer flow, 35 degrees C desolvation chamber temperature with approximately 45% organic modifier in the presence of 0.02-F ammonium acetate and a liquid chromatography flow rate of 0.2 mL/min. PMID- 24214304 TI - Ab initio calculations on 1,2-hydrogen shifts in the benzene radical cation and on carbon scrambling via an isomerization to the fulvene structure. AB - Multireference configuration interaction (MRCI//6-31G**) ab initio calculations show that the barrier for hydrogen scrambling in the benzene radical cation is about 50 kcal mol(-1). Once the internal energy is sufficient for a 1,2-hydrogen shift, the moving hydrogen can go to any position in the ring. The barrier for carbon scrambling via an isomerization to the fulvene structure is about 17 kcal mol(-1) higher than that for hydrogen scrambling. Both of these values are far below the dissociation limit. PMID- 24214305 TI - Determination of the anomeric configuration of glycosyl esters of nucleoside pyrophosphates by fast-atom bombardment tandem mass spectrometry. AB - Very low energy collision-induced dissociation of the deprotonated molecules of glycosyl esters of nucleoside pyrophosphates results in distinct fragmentation patterns that depend on the cis-trans configuration of the phosphodiester and 2" hydroxyl groups of the glycosyl residue. In tandem mass spectrometry, sugar nucleotides with cis configuration produce only one, very abundant fragment that corresponds to nucleoside monophosphate, whereas nucleotides with trans configuration give weak signals for the nucleoside di- and monophosphates and their dehydration products. This empirical rule holds for sugar nucleotides that have a free 2"-hydroxyl group and no alternative charge location. Owing to its simplicity, sensitivity, and tolerance of impurities, fast-atom bombardment tandem mass spectrometry represents a suitable method for determination of the anomeric linkage of glycosyl esters of nucleoside pyrophosphates if the absolute configuration of glycosyl residue is known and the compound fulfills the above mentioned requirements. PMID- 24214306 TI - An electrospray ionization mass spectrometry study of copper adducts of protonated ubiquitin. AB - A study of the addition of Cu(II) to a ubiquitin electrospray solution shows that the copper ion in the ubiquitin remains doubly charged and displaces two protons on the protonated protein molecule. This observation indicates a chelating bond between the protein and the Cu(II) species. The addition of Cu(I) also was studied and significant intensity was observed for adducts with up to four Cu(I) species attached, with each Cu(I) bonded to one basic site on the protein. PMID- 24214307 TI - Pentafluorobenzyl chloroformate derivatization for enhancement of detection of amino acids or alcohols by electron capture negative ion chemical ionization mass spectrometry. AB - Pentafluorobenzyl chloroformate (PFB-chloroformate) has been utilized as a derivatization reagent to impart electron affinity and provide structurally relevant fragmentation in electron capture negative ion chemical ionization mass spectrometry (ECNICI-MS). Phenylalanine (Phe) and decanol were used as model analytes. The conditions used for their derivatization and the chromatographic and mass spectrometric properties of the derivatives are reported. Phenylalanine in aqueous solution was derivatized in one step by using PFB-chloroformate and a mixture of water, ethanol, and pyridine. The phenylalanine N-pentafluorobenzyl oxycarbonyl ethyl ester (N-PFBC-Phe-OEt) exhibited good gas chromatographic properties and in ECNICI-MS, a dominant [M - 181](-) fragment carries most of the ion current. Selected ion monitoring experiments on N-PFBC-Phe-OEt resulted in the facile detection of 400 fmol of material. Decanol was derivatized by using anhydrous conditions, and the resultant pentafluorobenzyl carbonate also exhibited a predominant [M - 181](-) ion in ECNICI-MS. Initial results indicate that the ECNICI-MS molar response of the decyl pentafluorobenzyl carbonate derivative is six-fold that of the decyl pentafluorobenzoate. PMID- 24214308 TI - Ion-ion reactions in the gas phase: Proton transfer reactions of protonated pyridine with multiply charged oligonucleotide anions. AB - Isolated triply and doubly charged anions of the single-stranded deoxynucleotide 5'-d(AAAA)-3' were allowed to undergo ion-ion proton transfer reactions with protonated pyridine cations within a quadrupole ion trap mass spectrometer. Sufficiently high ion number densities and spatial overlap of the oppositely charged ion clouds could be achieved to yield readily measurable rates. Three general observations were made: (1) the ion-ion reaction rate constants were estimated to be 10(- (7 - 8)) cm(3) ion(-1) s(-1); (2) the ion-ion reaction rates were found to be dependent on the reactant ion number density, which could be controlled by both the reactant ion number and the pseudopotential well depth, and (3) very little fragmentation, if any, was observed, as might normally be expected with highly exothermic proton transfer reactions. PMID- 24214309 TI - High-resolution ion isolation with the ion cyclotron resonance capacitively coupled open cell. AB - For ion cyclotron resonance, a capacitively coupled open cell variant with fourfold radial symmetry was constructed and tested for axial excitation-ejection of large ions at high resolution. With a reverse of frequency sweep direction, this cell gave substantial improvements in signal-to-noise ratio due to linearization of the excitation electric field. Single isotopic peaks of ubiquitin (8.6-kDa) and carbonic anhydrase (29-kDa) molecular ions could be isolated by selective stored waveform inverse Fourier transform excitation, which yielded an order of magnitude higher isolation resolving power than previously achieved at high mass-to-charge ratio values. PMID- 24214310 TI - MS fundamentals self-paced training, version B : Produced by Hewlett-Packard, Palo Alto, CA Available through SAVANT Audiovisuals, Inc. 801 East Chapman Avenue, Fullerton, CA 92634 1993, 1995, $595. PMID- 24214312 TI - 3-Methylflavones characterization revisited: complete assignment of 1H and 13C NMR data. AB - Ten 3-methylflavone derivatives were studied. Previously reported NMR data of some derivatives were corrected and/or completed, including the complete assignment of the two known natural derivatives. The complete (1)H and (13)C NMR assignments were achieved by combination of one-dimensional and two-dimensional NMR experiments. PMID- 24214315 TI - Similar relationship between the time course of bone mineral density improvement and vertebral fracture risk reduction with denosumab treatment in postmenopausal osteoporosis and prostate cancer patients on androgen deprivation therapy. AB - Denosumab has received approval in many countries and indications include treating women with postmenopausal osteoporosis (PMO) at increased or high risk for fracture and men at high risk for fracture receiving androgen deprivation therapy (ADT) for non-metastatic prostate cancer. Increases in total hip bone mineral density (BMD) with denosumab explained a large percentage of new vertebral fracture risk reduction in women with PMO; however, this effect has not been studied in men with prostate cancer receiving ADT. We compared the relationship between the time course of BMD changes and new vertebral fracture risk reduction with denosumab in women with PMO and men with prostate cancer. After adjusting for different baseline hazards, a significant and similar relationship between time course of total hip and lumbar spine BMD changes and new vertebral fracture risk was observed in both patient populations. Time course of total hip BMD changes with denosumab was the best predictor for changes in fracture risk and explained 88% of the new vertebral fracture risk reduction in women with PMO and 91% in men with prostate cancer. Therefore, total hip BMD is a useful surrogate to measure the clinical impact of denosumab on fracture risk reduction in both patient populations. PMID- 24214316 TI - Systems biology-embedded target validation: improving efficacy in drug discovery. AB - The pharmaceutical industry is faced with a range of challenges with the ever escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. PMID- 24214318 TI - The unmet need for philanthropic funding of early career cardiovascular investigators. AB - Philanthropic donations have funded scientific investigations of cardiovascular disease for much of human history, and the patrons who enabled them are indirectly responsible for major breakthroughs in the field. Today, however, the lion's share of funding for cardiovascular research in Western countries comes from the government, professional agencies, and industry. Rapid budget cuts at these traditional sources of financial support are having a devastating impact on the cardiovascular research infrastructure by slashing funding for investigators. A particularly unfortunate consequence is the discouraging effect this is having on early career investigators, who are the life-blood of future breakthroughs in the field, leading to the potential loss of an entire generation of researchers. Here, we summarize the challenges faced by emerging cardiovascular investigators, make a case for the unmet need for appropriately targeted philanthropic support for cardiovascular research, and provide a roadmap for solving the funding shortfall for these investigators. PMID- 24214317 TI - Towards quantitation of the effects of renal impairment and probenecid inhibition on kidney uptake and efflux transporters, using physiologically based pharmacokinetic modelling and simulations. AB - BACKGROUND AND OBJECTIVES: The kidney is a major drug-eliminating organ. Renal impairment or concomitant use of transporter inhibitors may decrease active secretion and increase exposure to a drug that is a substrate of kidney secretory transporters. However, prediction of the effects of patient factors on kidney transporters remains challenging because of the multiplicity of transporters and the lack of understanding of their abundance and specificity. The objective of this study was to use physiologically based pharmacokinetic (PBPK) modelling to evaluate the effects of patient factors on kidney transporters. METHODS: Models for three renally cleared drugs (oseltamivir carboxylate, cidofovir and cefuroxime) were developed using a general PBPK platform, with the contributions of net basolateral uptake transport (T up,b) and apical efflux transport (T eff,a) being specifically defined. RESULTS AND CONCLUSION: We demonstrated the practical use of PBPK models to: (1) define transporter-mediated renal secretion, using plasma and urine data; (2) inform a change in the system-dependent parameter (>=10-fold reduction in the functional 'proximal tubule cells per gram kidney') in severe renal impairment that is responsible for the decreased secretory transport activities of test drugs; (3) derive an in vivo, plasma unbound inhibition constant of T up,b by probenecid (<=1 MUM), based on observed drug interaction data; and (4) suggest a plausible mechanism of probenecid preferentially inhibiting T up,b in order to alleviate cidofovir-induced nephrotoxicity. PMID- 24214319 TI - Women, resources, and dispersal in nineteenth-century Sweden. AB - In a recent study, female dispersal in nineteenth-century Sweden has been found to correlate negatively with access to resources: women with limited access to local resources tended to migrate more frequently. In this paper I review the literature to explore whether this observed correlation was derived from a relationship in which a woman's limited access to resources worsened her position in the marriage market and led to migration, as a strategy to improve resources and this position. Many studies within a variety of disciplines indicate that a woman's propensity to disperse from her parish of birth variedinversely with her propensity to inherit resources. My review of the literature suggests that the less likely a woman was to inherit resources, the lower her probability of marriage, the later her expected age at marriage, and the earlier she left home, presumably to improve her resource base for marriage. PMID- 24214320 TI - Trivers-willard rules for sex allocation : When do they maximize expected grandchildren in humans? AB - We present a quantitative model of sex allocation to investigate whether the simple "rules of thumb" suggested by Trivers and Willard (1973) would really maximize numbers of grandchildren in human populations. Using demographic data from the !Kung of southern Africa and the basic assumptions of the Trivers Willard hypothesis, we calculate expected numbers of grandchildren based on age- and sex-specific reproductive value. Patterns of parental investment that would maximize numbers of expected grandchildren often differ from the Trivers-Willard rules. In particular, the optimum parental behavior is sensitive to population dynamics, type of parental investment, and, most important, relative ages of sons and daughters. It is doubtful whether a parent blindly following the simple Trivers-Willard rules would maximize numbers of expected grandchildren, on average. In addition, we show that sex-specific infanticide will almost never achieve the goal of maximizing expected numbers of grandchildren. PMID- 24214321 TI - Relationships between the human sex ratio and the woman's microenvironment : Four tests. AB - Independent samples of women were surveyed to test Trivers and Willard's hypothesis that the mother's condition and her ability to invest in her offspring affect the (secondary) sex ratio of her offspring. Patterns of sex ratios (number of males per 100 females) were analyzed in conjunction with four attributes of a mother's microenvironment: level of health in her community, family structure, relative access to resources, and her birthing history. The results inferentially support the hypothesis that the microenvironment of the woman would act to bias the sex ratio of her offspring. These specific data lend support to Trivers and Willard's general hypothesis. PMID- 24214322 TI - Tattoos and male alliances. PMID- 24214323 TI - Hormonal changes accompanying sexual maturation in captive milkfish (Chanos chanos Forsskal). AB - Steroid hormone profiles accompanying sexual maturation in captive milkfish are described. There were no significant differences in levels of serum estradiol 17 beta (E2) and testosterone (T) between immature male and female fish. Mean E2 levels rose from 0.54+/-0.11 ng/ml in immature females (Stage 1) to 4.53+/-1.16 ng/ml in vitellogenic females (Stage 5), while T levels increased from 2.06+/ 0.28 ng/ml to 38.4+/-9.26 ng/ml. E2 and T levels were positively correlated to GSI and oocyte diameter. In males, serum T levels increased from 2.5+/-0.40 ng/ml in immature males to 27.73+/-5.02 ng/ml in spermiating males. A significantly higher T level was found in males with thick and scantly milt (spermiation index, SPI, 2) compared to males with scanty milt (SPI, 1) or males with copious, fluid milt (SPI, 3).Serum levels of E2 and T, and the GSI in females rose significantly during the breeding season (April-June 1983). The levels of both steroids dropped below 1 ng/ml in spent females sampled in succeeding months. In immature males, T levels ranged from 1.11 ng/ml to 2.78 ng/ml and rose significantly to 21.52+/ 8.38 ng/ml during the breeding season when GSI peaked. Serum T levels dropped to around 10 ng/ml in the succeeding months when only spent or regressed males were sampled. PMID- 24214324 TI - Angiotensins stimulate in vitro ovulation and contraction of brook trout (Salvelinus fontinalis) follicles. AB - The effects of salmon angiotensin I (sAI) and human angiotensin II (hAII) on in vitro ovulation of preovulatory (preOV) brook trout (Salvelinus fontinalis) follicles were investigated. Both angiotensins increased levels of ovulation above that in controls after 12 hours of incubation. The increase was statistically significant in incubates with greater than 1 MUM hAII. The effects of the angiotensins on follicle contraction were also studied indirectly by measuring the decrease in weight of punctured follicles taken prior to germinal vesicle breakdown. At 1 MUM, both angiotensins significantly decreased the weight of punctured follicles after 16 hours of incubation. The angiotensin-stimulated decrease in weight was not blocked by indomethacin (10 MUg/ml), indicating that follicle contraction was not prostaglandin-dependent. The data indicate that angiotensins might be directly involved in brook trout ovulation and the stimulatory effects of angiotensins on ovulation may be attributed to their effects on follicle contraction. PMID- 24214325 TI - Monosaccharides as energy resources during motility of spermatozoa in Leuciscus cephalus (Cyprinidae, Teleostei). AB - Spermatozoa of Leuciscus cephalus have the enzymatic outfit for glycolysis but lack lipase, phospholipase and glucosidase activities. Therefore, they are not able to utilize lipids and polysaccharides as energy resources. During motility they use monosaccharides as energy reservoirs: the intracellular glucose, galactose and fructose levels decrease significantly while lactate levels increase. PMID- 24214326 TI - The cytochrome P450 system of Atlantic salmon (Salmo salar): II. Variations in hepatic catalytic activities and isozyme patterns during an annual reproductive cycle. AB - A group of Atlantic salmon (Salmo salar) was followed through their first year of maturation and spawning. At monthly intervals, starting with juvenile fish in December, 5-7 fish of each sex were killed, and liver and plasma were sampled. The last sampling point was of spawning fish in November a year later. Variables in the cytochrome P450 (P450) system were studied in hepatic microsomes, and estradiol 17beta was measured in the plasma of females to assess the maturational status. The P450 1A1-mediated 7-ethoxyresorufin O-deethylase (EROD) started at high levels in winter, but decreased to non-detectable activities in pre-spawning females. Decreases, but not to the same extent, were also observed during this period in total cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, and in the content of two immunochemically determined P450 isozymes. At the same time, LSI levels increased in maturing females (starting in July), and GSI levels increased in both sexes (starting in May). Sex specific differences were observed in pre-spawning fish in September and October, with levels of total P450, b5, NADPH-cytochrome P450 reductase, EROD and P450 isozymes significantly lower in females. At the same time, plasma estradiol-17beta levels reached peak values in females. The results point to the important role of sex steroids such as estradiol-17beta as major factors in the regulation of final sexual maturation. However, this study also indicates that there may be estradiol-17beta independent events of equal importance in the early stages of gonadal maturation that may involve the P450 system. The changes observed in the P450 system (as a major drug and steroid metabolizing system) of Atlantic salmon during sexual maturation may be of importance both in the endogenous transduction of hormonal signals, and as a pharmacological basis for designing therapeutic treatment of diseases in the aquaculture industry. PMID- 24214327 TI - Utilization of dietary starch and glucose tolerance in juvenile chinook salmon (Oncorhynchus tshawytscha) of different strains in seawater. AB - Juvenile chinook salmon of three strains responded to inclusion of 28.7% of gelatinized starch in the diet with different degrees of reduction in growth rate and feed efficiency relative to control fish of the respective strains fed a low starch, high-lipid diet of similar protein (46%) and estimated metabolizable energy content (16 mJ/kg). The productive protein value of the diet was not reduced to the same extent by the high intake of starch. Carcasses of fish fed the high-starch diet contained higher concentrations of protein and lower concentrations of lipid than control fish. The accumulation of liver glycogen in response to the high-starch diet differed among strains. Glucose tolerance curves also varied among strains but were poorly correlated with plasma concentrations of insulin. Tolerance to glucose loading was improved in fish previously fed the high-starch diet. PMID- 24214328 TI - The minimum dietary requirement of vitamin C in Atlantic salmon (Salmo salar) fry using Ca ascorbate-2-monophosphate as dietary source. AB - The minimum dietary vitamin C requirement for optimal growth and normal development in Atlantic salmon (Salmo salar) fry at the onset of feeding was studied, using Ca ascorbate-2-monophosphate (AP) as dietary source. The requirement was established by means of a feeding study lasting for 23 weeks from the beginning of feeding. The practical diets used were supplemented with AP at levels of 0, 10, 20, 40, 80 and 160 mg ascorbic acid (AA) equivalents/kg. Growth, mortality, hydroxyproline content in skin and backbone, and AA in liver were recorded to evaluate the results. The results suggest that the minimum dietary requirement for optimal growth and normal development is in the range of 10-20 mg AA equivalents/kg dry diet during the period studied. PMID- 24214329 TI - The influence of dietary energy levels with and without PCB induction on the growth of tilapia, Oreochromis niloticos x O. aureus. AB - The effects of three dietary energy levels, 323, 365 and 408 Kcal/100g diet, on the growth performance of hybrid tilapia, Oreochromis niloticus x O. aureus, were studied. The experiment was carried out for 3 months in a recirculating rearing system. Growth and feed conversion ratios were significantly reduced (p<0.05) in fish exposed to 100 ppm polychlorinated biphenyl (PCB), fed high energy diets (365 and 408 Kcal/100g diet). The hepatic cytochrome P-450 and NADPH-cytochrome c reductase activities were also significantly (p<0.05) lower in PCB-treated fish fed high energy diets (365 and 408 Kcal/100g diet) than fish fed lower energy diet (323 Kcal/100g diet). The malic enzyme activity and the body lipid content in fish generally increased as the dietary energy level increased. PMID- 24214330 TI - Interrelationships between gill chloride cell morphology and calcium uptake in freshwater teleosts. AB - The involvement of the freshwater fish gill chloride cells (CCs) in trans branchial calcium uptake (JinCa(2+)) was investigated. This was accomplished by assessing the interspecific relationships between the apical surface area of CCs exposed to the external environment and JinCa(2+). Three species of freshwater teleosts, the rainbow trout (Oncorhynchus mykiss), the American eel (Anguilla rostrata) and the brown bullhead catfish (Ictalurus nebulosus), were used. Chronic (ten-day) treatment with cortisol in each species was used as a tool to evoke variations in both JinCa(2+) and gill CC morphology in order to assess intraspecific relationships between CC surface area and JinCa(2+). The results of quantitative morphometry, based on analysis of scanning electron micrographs, demonstrated that catfish possessed the lowest fractional area of exposed CC (CCFA) on the gill filament epithelium (12,744 +/- 2248 MUm(2)/mm(2)) and was followed, in increasing order, by American eel (21,355 +/- 981 MUm(2)/mm(2)) and rainbow trout (149,928 +/- 26,545 MUm(2)/mm(2)). With the exception of catfish, chronic treatment with cortisol caused significant increases in CCFA owing to proliferation of CCs and/or enlargement of individual CCs (eel only). The rates of JinCa(2+) closely reflected the CC fractional area in each species. The results of correlation analysis revealed significant correlations between CC fractional area and JinCa(2+) in trout and eel. Owing to the absence of an effect of cortisol treatment, there was no significant correlation in catfish because of insufficient variation in CC fractional area in this species. CC fractional area was significantly correlated with JinCa(2+) among the three species examined. These results suggest that CC is involved in calcium uptake in freshwater teleosts and that both intra- and interspecific differences in the rates of calcium uptake can be accounted for by variability in the surface area of exposed CCs on the gill epithelia. PMID- 24214331 TI - A specific inhibitor of mammalian kallikrein, Phe-Phe-Arg-chloromethyl ketone, inhibits the production of vasoactive substances from trout plasma by kallikrein and blocks endogenous kallikrein-like activity in trout gills. AB - The cardiovascular effects of the kallikrein-kinin system (KKS) have not been completely characterized in lower vertebrates. In the present study, a specific, irreversible kallikrein inhibitor, Phe-Phe-Arg-chloromethyl ketone (PPACMK) was used to examine: 1. the role of the KKS in blood pressure regulation in vivo; 2. the nature of the pressor substance formed by the action of kallikrein on trout plasma in vivo and in vitro; and 3. the presence of kallikrein in trout gills and kidney. Dorsal aortic cannulated rainbow trout were used for in vivo blood pressure assays and two colorimetric serine-protease assays were used to examine tissue kallikrein activity. PPACMK alone had no effect on blood pressure in vivo. Pretreatment of porcine kallikrein with PPACMK inhibited the enzyme's pressor effect in trout by 80% and significantly attenuated the synthesis of vasopressor substance(s) from heat-treated trout plasma in vitro. Approximately 30% of gill serine protease activity was inhibited by pretreatment with PPACMK; no PPACMK sensitive kallikrein activity was observed in the kidney. Salt water adaptation did not affect kallikrein-specific activity in the gill. These results show that the salmonid KKS does not appear to be involved in the regulation of systemic blood pressure. Further, the formation of pressor substances from trout plasma in vivo and in vitro is due to kallikrein activity and the peptides generated are similar. A kallikrein, similar to the mammalian enzyme, is found in trout gills, suggesting that the salmonid KKS may be a local mediator of gill function. PMID- 24214332 TI - Temperature shifts induce adaptive changes in the physical state of carp (Cyprinus carpio L.) erythrocyte plasma membranes in vitro. AB - Blood, freshly collected from warm- and cold-acclimated carp, Cyprinus carpio L., was cooled to 5 degrees C for 4h or warmed to 25 degrees C for 4h, respectively, and the fluorescence anisotropy of washed red blood cells was recorded using the fluorescent dye 3-(p-(6-phenyl-1,3,5-hexatrienyl) phenyl propionic acid [DPH-PA] (which is restricted to the outer leaflet of the plasma membrane) before and after the temperature shift. Despite individual variation, the plasma membrane of cold-exposed erythrocytes became more fluid while that of warm-exposed cells became more rigid following the temperature shift. This response was rapid and reversible. Cold-exposed cells from warm-acclimated fish became more fluid within 40-60 minutes and reverted to their original fluidity within the same time on warming, at a rate of 1 degrees C/min; erythrocytes, from cold-adapted carp displayed an opposite change in fluidity over a similar time period. Cells from warm-acclimated, temperature down-shifted carp hyperfluidized their plasma membranes in the cold, whereas cells from cold-acclimated fish up-shifted in temperature showed no similar effect. These cells showed a complete adjustment of membrane physical state to the temperature. Total phospholipids obtained from warm-acclimated temperature down-shifted cells became more rigid than they were, when assayed at the acclimation temperature. In contrast, phospholipids obtained from cold-acclimated cells became more rigid when exposed to increasing temperatures. No significant changes occurred to the polar head groups, or to the fatty acid composition of the total phospholipids. It was concluded that the lipids play only a secondary role in the control of the physical state of plasma membrane in carp erythrocytes, and that some non-lipid components of these structures might be involved in these regulatory processes. PMID- 24214333 TI - Chiral-at-metal octahedral iridium catalyst for the asymmetric construction of an all-carbon quaternary stereocenter. PMID- 24214334 TI - N2 and P3 potentials in early-onset and late-onset patients with obsessive compulsive disorder. AB - BACKGROUND: Impaired cognitive control processes may be central in the pathogenesis of obsessive-compulsive disorder (OCD). Our objective was to evaluate cognitive control processes with event-related potentials in early-onset OCD (EO) and late-onset OCD (LO), which are suggested to have distinct characteristics. METHODS: Participants were unmedicated EO (n = 26) and LO patients (n = 33) without comorbid psychopathology and healthy controls (n = 54). Go/No-go tasks with 50 and 80% Go trial probabilities were implemented to manipulate the strength of response conflict and inhibitory demands. RESULTS: LO patients had shorter N2 latencies than controls and did not show the N2 amplitude increase seen in controls with the increase in Go trial probability as suggestive of abnormal conflict monitoring processes. Both EO and LO patients showed smaller P3 increase than controls with the increase in Go trial probability, suggesting problems in modifying attentional control with changes in task demands. P3 was more anteriorly distributed in LO patients than controls. Additionally, P3 increase, with the increase in Go trial probability, was larger in frontal and central sites than in parietal sites in controls, whereas in EO patients it was almost homogenous across anteroposterior sites. CONCLUSIONS: N2 processes were affected only in LO, whereas P3 processes were affected in both EO and LO, although, somewhat differently. P3 distributions suggest that EO and LO patients have differences concerning the contributions of frontal and parietal components of attentional networks to the execution of Go/No-go tasks. Our results imply that EO and LO are distinct subtypes affecting the cognitive control systems differently. PMID- 24214335 TI - Drug-induced angioedema: experience of Italian emergency departments. AB - Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event. PMID- 24214336 TI - Serum uric acid is inversely proportional to estimated stroke volume and cardiac output in a large sample of pharmacologically untreated subjects: data from the Brisighella Heart Study. AB - Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14-84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p < 0.001), while gender, BMI, LDL cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p > 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = -0.219, p < 0.001) and between stroke volume and serum uric acid (B = -3.684, p < 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population. PMID- 24214337 TI - Meloxicam-induced thrombocytopenia. AB - Immune thrombocytopenia can have several causes including the use of certain drugs. Thrombocytopenia has been documented as a rare adverse effect of some nonsteroidal antiinflammatory drugs (NSAIDs) including diclofenac, naproxen, and ibuprofen. However, only one previously documented case of meloxicam-associated thrombocytopenia has been reported in the literature. We describe an 84-year-old woman who developed a case of immune-mediated thrombocytopenia that was attributed to meloxicam therapy. The patient's platelet count decreased from a baseline of 267 * 10(3) /mm(3) to 2 * 10(3) /mm(3) 1 week after she received her first lifetime dose of meloxicam. She also experienced black stools and bruising that coincided with the meloxicam administration. The almost immediate onset of thrombocytopenia and symptoms after initiation of meloxicam, as well as the marked reduction in her platelet count, suggest an idiosyncratic reaction. According to the Hill criteria for assessing causality of adverse drug events, it is plausible that this reaction was due to meloxicam. Health care providers should be aware of the possibility of thrombocytopenia secondary to NSAID therapy including meloxicam. Immune thrombocytopenia can be life threatening if it is not identified and treated promptly. A thorough medication history is particularly important when patients present with unusual symptoms, with a focus on those drugs that have been recently initiated. Although thrombocytopenia is a rare adverse effect of NSAID therapy, it should be considered a potential cause in patients receiving these drugs who have signs and symptoms consistent with this blood dyscrasia. PMID- 24214338 TI - DNA methylation and demethylation: a pathway to gametogenesis and development. AB - The generation of gametes falls between two reprogramming phases. These phases are characterised by profound periods of transcriptional activity, which define and reinforce lineage decisions. The control of these transcriptional programs and the interpretation of the underlying genetic instruction is the task of the epigenome. As such, dynamic processes during reprogramming are critical for the development of the germ line and its resetting, which propels that developmental process forward and provides the transfer of genetic and epigenetic information between generations. Central in this reprogramming is the addition and subtraction of DNA methylation and its oxidative products, coupled to the mechanisms at play to achieve this goal. The activities competent to add DNA methylation, and identification of those enzymes able to modify it, have heralded a new chapter in our understanding of the complexities that dictate and direct cellular fates. How the early embryos makes use of these marks and how they are modulated will give us insight into cellular differentiation and reprogramming critical for health and into the process of aging. This review details some of these processes and the activities essential to achieve the immortality of the mammalian germ line. PMID- 24214339 TI - Recombination and annealing pathways compete for substrates in making rrn duplications in Salmonella enterica. AB - Tandem genetic duplications arise frequently between the seven directly repeated 5.5-kb rrn loci that encode ribosomal RNAs in Salmonella enterica. The closest rrn genes, rrnB and rrnE, flank a 40-kb region that includes the purHD operon. Duplications of purHD arise by exchanges between rrn loci and form at a high rate (10(-3)/cell/division) that remains high in strains blocked for early steps in recombination (recA, recB, and/or recF), but drops 30-fold in mutants blocked for later Holliday junction resolution (ruvC recG). The duplication defect of a ruvC recG mutant was fully corrected by an added mutation in any one of the recA, recB, or recF genes. To explain these results, we propose that early recombination defects activate an alternative single-strand annealing pathway for duplication formation. In wild-type cells, rrn duplications form primarily by the action of RecFORA on single-strand gaps. Double-strand breaks cannot initiate rrn duplications because rrn loci lack Chi sites, which are essential for recombination between two separated rrn sequences. A recA or recF mutation allows unrepaired gaps to accumulate such that different rrn loci can provide single strand rrn sequences that lack the RecA coating that normally inhibits annealing. A recB mutation activates annealing by allowing double-strand ends within rrn to avoid digestion by RecBCD and provide a new source of rrn ends for use in annealing. The equivalent high rates of rrn duplication by recombination and annealing pathways may reflect a limiting economy of gaps and breaks arising in heavily transcribed, palindrome-rich rrn sequences. PMID- 24214340 TI - Implicating SCF complexes in organogenesis in Caenorhabditis elegans. AB - Development of the Caenorhabditis elegans foregut (pharynx) is regulated by a network of proteins that includes the Retinoblastoma protein (pRb) ortholog LIN 35; the ubiquitin pathway components UBC-18 and ARI-1; and PHA-1, a cytoplasmic protein. Loss of pha-1 activity impairs pharyngeal development and body morphogenesis, leading to embryonic arrest. We have used a genetic suppressor approach to dissect this complex pathway. The lethality of pha-1 mutants is suppressed by loss-of-function mutations in sup-35/ztf-21 and sup-37/ztf-12, which encode Zn-finger proteins, and by mutations in sup-36. Here we show that sup-36 encodes a divergent Skp1 family member that binds to several F-box proteins and the microtubule-associated protein PLT-1/tau. Like SUP-35, SUP-36 levels were negatively regulated by UBC-18-ARI-1. We also found that SUP-35 and SUP-37 physically associated and that SUP-35 could bind microtubules. Thus, SUP 35, SUP-36, and SUP-37 may function within a pathway or complex that includes cytoskeletal components. Additionally, SUP-36 may regulate the subcellular localization of SUP-35 during embryogenesis. We carried out a genome-wide RNAi screen to identify additional regulators of this network and identified 39 genes, most of which are associated with transcriptional regulation. Twenty-three of these genes acted via the LIN-35 pathway. In addition, several S-phase kinase associated protein (Skp)1-Cullin-F-Box (SCF) components were identified, further implicating SCF complexes as part of the greater network controlling pharyngeal development. PMID- 24214341 TI - Dual phosphorylation of cdk1 coordinates cell proliferation with key developmental processes in Drosophila. AB - Eukaryotic organisms use conserved checkpoint mechanisms that regulate Cdk1 by inhibitory phosphorylation to prevent mitosis from interfering with DNA replication or repair. In metazoans, this checkpoint mechanism is also used for coordinating mitosis with dynamic developmental processes. Inhibitory phosphorylation of Cdk1 is catalyzed by Wee1 kinases that phosphorylate tyrosine 15 (Y15) and dual-specificity Myt1 kinases found only in metazoans that phosphorylate Y15 and the adjacent threonine (T14) residue. Despite partially redundant roles in Cdk1 inhibitory phosphorylation, Wee1 and Myt1 serve specialized developmental functions that are not well understood. Here, we expressed wild-type and phospho-acceptor mutant Cdk1 proteins to investigate how biochemical differences in Cdk1 inhibitory phosphorylation influence Drosophila imaginal development. Phosphorylation of Cdk1 on Y15 appeared to be crucial for developmental and DNA damage-induced G2-phase checkpoint arrest, consistent with other evidence that Myt1 is the major Y15-directed Cdk1 inhibitory kinase at this stage of development. Expression of non-inhibitable Cdk1 also caused chromosome defects in larval neuroblasts that were not observed with Cdk1(Y15F) mutant proteins that were phosphorylated on T14, implicating Myt1 in a novel mechanism promoting genome stability. Collectively, these results suggest that dual inhibitory phosphorylation of Cdk1 by Myt1 serves at least two functions during development. Phosphorylation of Y15 is essential for the premitotic checkpoint mechanism, whereas T14 phosphorylation facilitates accumulation of dually inhibited Cdk1-Cyclin B complexes that can be rapidly activated once checkpoint arrested G2-phase cells are ready for mitosis. PMID- 24214342 TI - Environment determines epistatic patterns for a ssDNA virus. AB - Despite the accumulation of substantial quantities of information about epistatic interactions among both deleterious and beneficial mutations in a wide array of experimental systems, neither consistent patterns nor causal explanations for these interactions have yet emerged. Furthermore, the effects of mutations depend on the environment in which they are characterized, implying that the environment may also influence epistatic interactions. Recent work with beneficial mutations for the single-stranded DNA bacteriophage ID11 demonstrated that interactions between pairs of mutations could be understood by means of a simple model that assumes that mutations have additive phenotypic effects and that epistasis arises through a nonlinear phenotype-fitness map with a single intermediate optimum. To determine whether such a model could also explain changes in epistatic patterns associated with changes in environment, we measured epistatic interactions for these same mutations under conditions for which we expected to find the wild-type ID11 at different distances from its phenotypic optimum by assaying fitnesses at three different temperatures: 33 degrees , 37 degrees , and 41 degrees . Epistasis was present and negative under all conditions, but became more pronounced as temperature increased. We found that the additive-phenotypes model explained these patterns as changes in the parameters of the phenotype-fitness map, but that a model that additionally allows the phenotypes to vary across temperatures performed significantly better. Our results show that ostensibly complex patterns of fitness effects and epistasis across environments can be explained by assuming a simple structure for the genotype-phenotype relationship. PMID- 24214343 TI - Estimation of the spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family. AB - We employed deep genome sequencing of two parents and 12 of their offspring to estimate the mutation rate per site per generation in a full-sib family of Drosophila melanogaster recently sampled from a natural population. Sites that were homozygous for the same allele in the parents and heterozygous in one or more offspring were categorized as candidate mutations and subjected to detailed analysis. In 1.23 * 10(9) callable sites from 12 individuals, we confirmed six single nucleotide mutations. We estimated the false negative rate in the experiment by generating synthetic mutations using the empirical distributions of numbers of nonreference bases at heterozygous sites in the offspring. The proportion of synthetic mutations at callable sites that we failed to detect was <1%, implying that the false negative rate was extremely low. Our estimate of the point mutation rate is 2.8 * 10(-9) (95% confidence interval = 1.0 * 10(-9) - 6.1 * 10(-9)) per site per generation, which is at the low end of the range of previous estimates, and suggests an effective population size for the species of ~1.4 * 10(6). At one site, point mutations were present in two individuals, indicating that there had been a premeiotic mutation cluster, although surprisingly one individual had a G->A transition and the other a G->T transversion, possibly associated with error-prone mismatch repair. We also detected three short deletion mutations and no insertions, giving a deletion mutation rate of 1.2 * 10(-9) (95% confidence interval = 0.7 * 10(-9) - 11 * 10( 9)). PMID- 24214345 TI - General triallelic frequency spectrum under demographic models with variable population size. AB - It is becoming routine to obtain data sets on DNA sequence variation across several thousands of chromosomes, providing unprecedented opportunity to infer the underlying biological and demographic forces. Such data make it vital to study summary statistics that offer enough compression to be tractable, while preserving a great deal of information. One well-studied summary is the site frequency spectrum-the empirical distribution, across segregating sites, of the sample frequency of the derived allele. However, most previous theoretical work has assumed that each site has experienced at most one mutation event in its genealogical history, which becomes less tenable for very large sample sizes. In this work we obtain, in closed form, the predicted frequency spectrum of a site that has experienced at most two mutation events, under very general assumptions about the distribution of branch lengths in the underlying coalescent tree. Among other applications, we obtain the frequency spectrum of a triallelic site in a model of historically varying population size. We demonstrate the utility of our formulas in two settings: First, we show that triallelic sites are more sensitive to the parameters of a population that has experienced historical growth, suggesting that they will have use if they can be incorporated into demographic inference. Second, we investigate a recently proposed alternative mechanism of mutation in which the two derived alleles of a triallelic site are created simultaneously within a single individual, and we develop a test to determine whether it is responsible for the excess of triallelic sites in the human genome. PMID- 24214346 TI - The psychophysical assessment of odor valence: does an anchor stimulus influence the hedonic evaluation of odors? AB - Olfactory stimuli are experienced primarily in terms of their hedonic tone and the assessment of olfactory hedonic estimates is a prevalent task in scientific and industrial contexts. However, measuring conditions are poorly standardized. Our study aims to fill this gap, focusing on the influence of anchor stimuli on olfactory hedonic evaluations, frequency of anchor presentation, and temporal stability of results. In n = 31 subjects, hedonic estimates for the 16 odors of the Sniffin' Sticks identification task were assessed on a visual analog rating scale under 4 measuring conditions (nonanchor, pleasant anchor, neutral anchor, unpleasant anchor). To test for stability over time, n = 10 subjects were reassessed 2, 4, and 6 months after original testing. To analyze for possible effects of single versus repeated anchor presentation, n = 15 subjects were retested 2 months after the original session in a multiple anchor presentation format. Statistical analysis revealed significant differences between the 4 anchor conditions, thus highlighting the necessity of specifying assessment methods in scientific research. No significant differences between timepoints were observed, indicating a high temporal stability of olfactory hedonic evaluations, especially from timepoint T2 onward. No overall significant effects of single versus multiple anchor presentation were detected. Findings might help to further standardize testing procedures. PMID- 24214344 TI - Insights into dynamic mitotic chromatin organization through the NIMA kinase suppressor SonC, a chromatin-associated protein involved in the DNA damage response. AB - The nuclear pore complex proteins SonA and SonB, the orthologs of mammalian RAE1 and NUP98, respectively, were identified in Aspergillus nidulans as cold sensitive suppressors of a temperature-sensitive allele of the essential mitotic NIMA kinase (nimA1). Subsequent analyses found that sonB1 mutants exhibit temperature-dependent DNA damage sensitivity. To understand this pathway further, we performed a genetic screen to isolate additional conditional DNA damage sensitive suppressors of nimA1. We identified two new alleles of SonA and four intragenic nimA mutations that suppress the temperature sensitivity of the nimA1 mutant. In addition, we identified SonC, a previously unstudied binuclear zinc cluster protein involved with NIMA and the DNA damage response. Like sonA and sonB, sonC is an essential gene. SonC localizes to nuclei and partially disperses during mitosis. When the nucleolar organizer region (NOR) undergoes mitotic condensation and removal from the nucleolus, nuclear SonC and histone H1 localize in a mutually exclusive manner with H1 being removed from the NOR region and SonC being absent from the end of the chromosome beyond the NOR. This region of chromatin is adjacent to a cluster of nuclear pore complexes to which NIMA localizes last during its progression around the nuclear envelope during initiation of mitosis. The results genetically extend the NIMA regulatory system to include a protein with selective large-scale chromatin location observed during mitosis. The data suggest a model in which NIMA and SonC, its new chromatin-associated suppressor, might help to orchestrate global chromatin states during mitosis and the DNA damage response. PMID- 24214347 TI - Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1. AB - Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present. PMID- 24214349 TI - 3q29 microdeletion syndrome: Cognitive and behavioral phenotype in four patients. AB - The 3q29 microdeletion syndrome is a rare, recurrent genomic disorder, associated with a variable phenotype, despite the same deletion size, consisting in neurodevelopmental features, such as intellectual disability (ID), schizophrenia, autism, bipolar disorder, depression and mild facial morphological anomalies/congenital malformations. A thorough neuropsychiatric evaluation has never been reported in patients with such syndrome. We analyzed the clinical phenotype of four individuals with 3q29 microdeletion syndrome, with special emphasis on the cognitive and behavioral assessment, in order to delineate the neuropsychiatric phenotype related to this condition. We assessed these patients with standardized scales or checklists measuring the cognitive (WISC III or LIPS R), behavioral (CBCL) and adaptive (VABS) performances. An accurate evaluation in our sample highlights different degrees of ID, variable behavioral disorders, and a preservation of communicative skills among remaining adaptive areas, as the neuropsychiatric hallmark of 3q29 microdeletion syndrome. PMID- 24214348 TI - Studies to analyse the relationship between IFNalpha2b gene dosage and its expression, using a Pichia pastoris-based expression system. AB - Human interferon alpha2b (hIFNalpha2b) is the most important member of the interferon family. Escherichia coli, yeasts, mammalian cell cultures and baculovirus-infected insect cells have been used for expressing recombinant human interferon. Recently a Pichia pastoris-based expression system has emerged as an attractive system for producing functional human recombinant IFNalpha2b. In this regard, gene dosage is considered an important factor in obtaining the optimum expression of recombinant protein, which may vary from one protein to another. In the present study we have shown the effect of IFNalpha2b gene dosage on extracellular expression of IFNalpha2b recombinant protein from P. pastoris. Constructs containing from one to five repeats of IFNalpha2b-expressing cassettes were created via an in vitro multimerization approach. P. pastoris host strain X 33 was transformed using these expression cassettes. Groups of P. pastoris clones transformed with different copies of the IFNalpha2b expression cassette were screened for intrachromosomal integration. The IFNalpha2b expression level of stable transformants was checked. The copy number of integrated IFNalpha2b was determined by performing qPCR of genomic DNA of recombinant P. patoris clones. It was observed that an increase in copy number generally had a positive effect on the expression level of IFNalpha2b protein. Regarding the performance of multicopy strains, those obtained from transformation of multicopy vectors showed relatively high expression, compared to those generated using transformation vector having only one copy of IFNalpha2b. It was also observed that an increase in drug resistance of a clone did not guarantee its high expression, as integration of a marker gene did not always correlate with integration of the gene of interest. PMID- 24214351 TI - Collisional relaxation of metastable electronic states of Fe(+). AB - The overall rate constants for collisional relaxation of metastable excited states of Fe(+) by He, Ar, Kr, H2, (2)H2, CO, N2, NO, CH4, and CH3OH have been studied by using charge-exchange ion-molecule reaction chemistry. The rate constants vary according to the nature of the quenching reagent as well as the energy level and electron configuration of the Fe(+) ions. In general, NO, CH4, and CH3OH are the most efficient quenching reagents with rate constants that approach the Langevin collision rate, whereas the reaction rates for the rare gas atoms are slow and vary depending upon the specific electron configuration of the Fe(+) ion. The mechanism of collisional relaxation is discussed with emphasis on a curve-crossing. mechanism for the rare gas atoms. An electron-transfer mechanism is described for the relaxation of high lying (Fe(+))*. PMID- 24214352 TI - The ionized methylene transfer from the distonic radical cation (+)CH 2-O-CH 2 to heterocyclic compounds. A pentaquadrupole mass spectrometric study. AB - Ion-molecule reactions of the mass-selected distonic radical cation (+)CH2-O-CH 2 (.) (1) with several heterocyclic compounds have been investigated by multiple stage mass spectro- metric experiments performed in a pentaquadrupole mass spectrometer. Reactions with pyridine, 2-, 3-, and 4-ethyl, 2-methoxy, and 2-n propyl pyridine occur mainly by transfer of CH 2 (+.) to the nitrogen, which yields distonic N-methylene-pyridinium radical cations. The MS(3) spectra of these products display very characteristic collision-induced dissociation chemistry, which is greatly affected by the position of the substituent in the pyridine ring. Ortho isomers undergo a delta-cleavage cyclization process induced by the free-radical character of the N-methylene group that yields bicyclic pyridinium cations. On the other hand, extensive CH 2 (+.) transfer followed by rapid hydrogen atom loss, that is, a net CH(+) transfer, occurs not to the heteroatoms, but to the aromatic ring of furan, thiophene, pyrrole, and N-methyl pyrrole. The reaction proceeds through five- to six-membered ring expansion, which yields the pyrilium, thiapyrilium, N-protonated, and N-methylated pyridine cations, respectively, as indicated by MS(3) scans. Ion 1 fails to transfer CH 2 (+.) to tetrahydrofuran, whereas a new alpha-distonic sulfur ion is formed in reactions with tetrahydrothiophene. Unstable N-methylene distonic ions, likely formed by transfer of CH 2 (+.) to the nitrogen of piperidine and pyrrolidine, undergo rapid fragmentation by loss of the alpha-NH hydrogen to yield closed shell immonium cations. The most thermodynamically favorable products are formed in these reactions, as estimated by ab initio calculations at the MP2/6 31G(d,p)//6-31G(d,p) + ZPE level of theory. PMID- 24214353 TI - Remeasurement at high resolving power in fourier transform ion cyclotron resonance mass spectrometry. AB - The Fourier transform ion cyclotron resonance mass spectrometry remeasurement experiment is demonstrated and evaluated under high resolution conditions. Signal to-noise enhancement is observed for isotopically resolved bovine insulin peaks at a resolution of ~ 31,000 (full width at half height). The experiment is sensitive to spacecharge effects and resultant changes in scan-to-scan signal-to noise and resolution. Coulombic repulsion in the ion cloud during the high resolution remeasurement experiment can cause the cyclotron frequency to shift through the duration of the experiment, which results in broadened peak shapes when individual remeasurement spectra are coadded. By either reducing the number of ions in the cell or allowing the ion cloud to diffuse during the lifetime of the experiment, high resolution remeasurement spectra can be coadded without peak broadening or degradation of signal-to-noise ratio. PMID- 24214350 TI - Longitudinal in vivo two-photon fluorescence imaging. AB - Fluorescence microscopy is an essential technique for the basic sciences, especially biomedical research. Since the invention of laser scanning confocal microscopy in the 1980s, which enabled imaging both fixed and living biological tissue with 3D precision, high-resolution fluorescence imaging has revolutionized biological research. Confocal microscopy, by its very nature, has one fundamental limitation. Due to the confocal pinhole, deep tissue fluorescence imaging is not practical. In contrast (no pun intended), two-photon fluorescence microscopy allows, in principle, the collection of all emitted photons from fluorophores in the imaged voxel, dramatically extending our ability to see deep into living tissue. Since the development of transgenic mice with genetically encoded fluorescent protein in neocortical cells in 2000, two-photon imaging has enabled the dynamics of individual synapses to be followed for up to 2 years. Since the initial landmark contributions to this field in 2002, the technique has been used to understand how neuronal structure are changed by experience, learning, and memory and various diseases. Here we provide a basic summary of the crucial elements that are required for such studies, and discuss many applications of longitudinal two-photon fluorescence microscopy that have appeared since 2002. PMID- 24214354 TI - Low flow high-performance liquid chromatography solvent delivery system designed for tandem capillary liquid chromatography-mass spectrometry. AB - A solvent delivery system is described that is designed to increase the efficiency of liquid chromatography-mass spectrometry (LC/MS) analyses. Gradients formed by using two low pressure syringe pumps are stored in a length of narrow bore tubing (gradient loop) mounted on a standard high pressure switching valve. The preformed gradient is pushed through the column by using a high pressure syringe pump. The system is fully automated and can be controlled with either a personal computer or the mass spectrometer data system. Advantages include gradient operation without the use of split flows, pressure programed flow control for rapid sample loading and recycling to initial conditions, and a flow rate range of 0.1-20 MUL/min, which is suitable for packed capillary columns 50 500 MUm in diameter. The system has been used extensively for rapid molecular weight determinations of intact protein samples, as well as LC/MS and liquid chromatography-tandem mass spectrometry analyses of complex peptide mixtures. PMID- 24214355 TI - Photodissociation of high molecular weight peptides and proteins in a two-stage linear time-of-flight mass spectrometer. AB - A two-stage linear time-of-flight mass spectrometer is used to investigate the requirements for performance of laser photodissociation of peptide and protein ions. Results are presented that demonstrate that desorption and dissociation laser pulses can be synchronized to irradiate ions that travel at high velocities down the drift tube of a time-of-flight mass spectrometer. For example, 193-nm photodissociation of bovine insulin and doubly charged lysozyme is demonstrated, and laser power studies suggest that dissociation is initiated by the absorption of a single 193-nm photon. These results are encouraging because they suggest that laser photodissociation of high molecular weight proteins can lead to fragmentation on time scales compatible with time-of-flight mass spectrometry. PMID- 24214356 TI - Fast-atom bombardment mass spectrometry and low energy collision-induced tandem mass spectrometry of tauroconjugated bile acid anions. AB - Fragmentation of negative ions produced by fast-atom bombardment (FAB) from 14 tauroconjugated bile acids and some of their deuterated analogs has been studied by mass spectrometry and by collision-induced dissociation (CED) tandem mass spectrometry at low energy.Low energy collision-induced dissociation of the deprotonated molecules [M - H](-) of these tauroconjugated bile acids leads to both charge-driven and charge-remote fragmentations (CRF). The former yields neutral loss from the side chain with charge migration during the fragmentation process. These fragments dominate the CID spectra, but are absent from the FAB spectra. Their relative abundances are dependent on the number and the positions of the hydroxyl groups in the steroid nucleus and thus permit distinction among some positional isomers.The CRF fragments correspond to cleavages in the side chain up to fragmentations across the steroid rings with charge retention on the sulfonate group. These CRF fragments, which also are useful for structural identification, are less intense in CID than in FAB spectra. It appears that these charge-remote fragments are favored by unsaturation in the steroid rings, either as keto groups or as endocyclic double bonds. Tandem mass spectrometry combined with the use of deuterated analogs demonstrates that the structures of the survivor pseudomolecular ions and of the CRF fragments are not rearranged. PMID- 24214357 TI - Measurement of high-molecular-weight polycyclic aromatic hydrocarbons in soils by particle beam high-performance liquid chromatography-mass spectrometry. AB - Polycyclic aromatic hydrocarbons (PAHs) comprise a class of potentially hazardous com- pounds of concern to the U.S. EPA. The application of particle-beam (PB) liquid chromatography-mass spectrometry (LC-MS) to the measurement of high molecular-weight PAHs was investigated. Instrument performance was evaluated for 16 PAHs in the molecular weight range 300-450 u. The PAHs were separated by reverse-phase high-performance liquid chromatography via a polymeric octadecylsilica (C-18) packing and gradient elution with methanol tetrahydrofuran. On-column instrument detection limits, as measured by selected ion monitoring on the singly charged molecular ion of each PAH, were found to be 0.15-0.60 ng for PAHs with molecular weights up to 352 u and 2-4 ng for PAHs with molecular weights greater than 352 u. Instrument response was generally linear for PAHs with molecular weights 300-352 u and generally nonlinear for PAHs with molecular weights greater than 352 u. The PB electron impact mass spectra of the PAHs were found to vary with the ion distribution ratio of the singly charged molecular ion to the doubly charged molecular ion, dependent on molecular weight, ion source temperature, and concentration. Analysis by PB LC-MS was applied to extracts of PAH-spiked soil and a PAH-contaminated soil from the Pacific Northwest. Target analyte concentrations in the PAH-contaminated soil ranged from 0.85 to 84 ug/g. Quantitative estimates for nontarget PAHs also were determined. Analysis of a second soil extract from a hazardous waste site in the northeast part of the United States displayed isomeric patterns of high-molecular-weight PAHs similar to those of the Pacific Northwest extract. PMID- 24214358 TI - On the use of scans at a constant ratio of B/E for studying decompositions of peptide metal(II)-ion complexes formed by electrospray ionization. AB - The use of sector mass spectrometers to study metastable ion decompositions of peptide metal-ion complexes formed by electrospray ionization is discussed. Products that are formed by charge-separation reactions are characterized by large kinetic energy release distributions. This causes scans at a constant B/E to give incorrect product ion abundances and possibly incorrect mass assignments. Two instrumental methods exist that can be used either to detect the ions or to estimate relative ion abundances: a floated collision cell or mass-analyzed ion kinetic energy spectrometry (MIKES) scans. The floated collision cell, by virtue of an altered B/E scan law, however, discriminates against important metastable ion reactions that occur outside the cell. MIKES scans provide a clearer estimate of product ions that arise by metastable ion charge-separation reactions. Problems with pseudotandem (first field-free region) experiments are also discussed. PMID- 24214359 TI - Mass spectrometry PittCon '95. PMID- 24214361 TI - A structure-guided approach for protein pocket modeling and affinity prediction. AB - Binding affinity prediction is frequently addressed using computational models constructed solely with molecular structure and activity data. We present a hybrid structure-guided strategy that combines molecular similarity, docking, and multiple-instance learning such that information from protein structures can be used to inform models of structure-activity relationships. The Surflex-QMOD approach has been shown to produce accurate predictions of binding affinity by constructing an interpretable physical model of a binding site with no experimental binding site structural information. We introduce a method to integrate protein structure information into the model induction process in order to construct more robust physical models. The structure-guided models accurately predict binding affinities over a broad range of compounds while producing more accurate representations of the protein pockets and ligand binding modes. Structure-guidance for the QMOD method yielded significant performance improvements, both for affinity and pose prediction, especially in cases where predictions were made on ligands very different from those used for model induction. PMID- 24214362 TI - Robotic modified radical neck dissection by bilateral axillary breast approach for papillary thyroid carcinoma with lateral neck metastasis. AB - BACKGROUND: The purpose of this study was to evaluate the safety of robotic modified radical neck dissection compared to open modified radical neck dissection. METHODS: We enrolled 78 patients who were diagnosed with papillary thyroid cancer and underwent total thyroidectomy, bilateral central neck dissection, and modified radical neck dissection between March 2011 and February 2013. Of these patients, 65 underwent an open procedure and 13 underwent a robotic procedure using the bilateral axillary breast approach (BABA). These 2 groups were retrospectively compared. RESULTS: The mean age, sex, body mass index (BMI), and tumor size were not significantly different between groups. There were no differences in the number of retrieved lymph nodes, metastatic lymph nodes, or stimulated thyroglobulin level between the 2 groups. The operation time was longer in the robotic group than in the open group. CONCLUSION: Robotic modified radical neck dissection using BABA is safe and shows oncologic and postoperative outcomes comparable to those of the open procedure. PMID- 24214363 TI - Similarity of geleophysic dysplasia and Weill-Marchesani syndrome. AB - The acromelic dysplasias comprise short stature, hands and feet, and stiff joints. Three disorders are ascribed to this group, namely Weill-Marchesani syndrome, geleophysic dysplasia, and acromicric dysplasia, although similar in phenotype, can be distinguished clinically. Weill-Marchesani syndrome, on the basis of microspherophakia and ectopia lentis; geleophysic dysplasia by progressive cardiac valvular thickening, tracheal stenosis, and/or bronchopulmonary insufficiency, often leading to early death. Microspherophakia has not been reported previously in geleophysic dysplasia. Mutations in FBN1, ADAMTS10, or ADAMTS17 cause Weill-Marchesani syndrome by disrupting the microfibrillar environment, while geleophysic dysplasia is associated with enhanced TGF-beta signaling mediated through mutations in FBN1 or ADAMTSL2. We studied a 35-year-old woman with geleophysic dysplasia, with short stature, small hands and feet, limitation of joint mobility, mild skin thickening, cardiac valvular disease, restrictive pulmonary disease, and microspherophakia. Sequencing of ADAMTSL2 demonstrated two changes: IVS8-2A>G consistent with a disease-causing mutation, and IVS14-7G>A with potential to generate a new splice acceptor site and result in aberrant mRNA processing. The unaffected mother carries only the IVS8-2A>G transition providing evidence that the two changes are in trans-configuration in our patient. PMID- 24214365 TI - Sexual selection and physical attractiveness : Implications for mating dynamics. AB - Sexual selection processes have received much attention in recent years, attention reflected in interest in human mate preferences. Among these mate preferences are preferences for physical attractiveness. Preferences in and of themselves, however, do not fully explain the nature of the relationships that individuals attain. A tacit negotiation process underlies relationship formation and maintenance. The notion that preferences for physical attractiveness evolved under parasite-driven "good genes" sexual selection leads to predictions about the nature of trade-offs that individuals make between mates' physical attractiveness and investment potential. These predictions and relevant data are explored, with a primary emphasis on women's preferences for men's qualities. In addition, further implications of trade-offs are examined, most notably (a) the impact of environmental variations on the nature of mating and (b) some effects of trade-offs on infidelity and male attempts to control women. PMID- 24214364 TI - Should mild COPD be treated? Evidence for early pharmacological intervention. AB - Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways that is both preventable and treatable. It is well established that those with mild-to-moderate disease severity represent the majority of patients with COPD, yet this subpopulation is relatively under studied. Because of an insidious pre-clinical phase, COPD is both under-diagnosed and under-treated. Recent studies have confirmed that even patients with mild, grade 1 COPD [i.e. those with a reduced forced expiratory volume in one second (FEV1)/forced vital capacity ratio but normal FEV1], have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with non-smoking healthy controls. Beyond the imperative of smoking cessation-the pivotal intervention in all COPD stages-the role of pharmacotherapy for prevention of disease progression has yet to be established. The main objective of this review is to provide a concise overview of the heterogeneous pathophysiology of COPD with only mild airway obstruction on spirometry and obstacles for early diagnosis. We emphasize that the absence of sufficiently powered trials involving a large number of patients precludes definitive recommendations in support of (or against) long-term pharmacological treatment in mild COPD. Despite these limitations, we present a rationale for earlier pharmacological intervention derived from recent physiological studies performed in symptomatic patients with mild COPD. PMID- 24214366 TI - Human facial beauty : Averageness, symmetry, and parasite resistance. AB - It is hypothesized that human faces judged to be attractive by people possess two features-averageness and symmetry-that promoted adaptive mate selection in human evolutionary history by way of production of offspring with parasite resistance. Facial composites made by combining individual faces are judged to be attractive, and more attractive than the majority of individual faces. The composites possess both symmetry and averageness of features. Facial averageness may reflect high individual protein heterozygosity and thus an array of proteins to which parasites must adapt. Heterozygosity may be an important defense of long-lived hosts against parasites when it occurs in portions of the genome that do not code for the essential features of complex adaptations. In this case heterozygosity can create a hostile microenvironment for parasites without disrupting adaptation. Facial bilateral symmetry is hypothesized to affect positive beauty judgments because symmetry is a certification of overall phenotypic quality and developmental health, which may be importantly influenced by parasites. Certain secondary sexual traits are influenced by testosterone, a hormone that reduces immunocompetence. Symmetry and size of the secondary sexual traits of the face (e.g., cheek bones) are expected to correlate positively and advertise immunocompetence honestly and therefore to affect positive beauty judgments. Facial attractiveness is predicted to correlate with attractive, nonfacial secondary sexual traits; other predictions from the view that parasite-driven selection led to the evolution of psychological adaptations of human beauty perception are discussed. The view that human physical attractiveness and judgments about human physical attractiveness evolved in the context of parasite driven selection leads to the hypothesis that both adults and children have a species-typical adaptation to the problem of identifying and favoring healthy individuals and avoiding parasite-susceptible individuals. It is proposed that this adaptation guides human decisions about nepotism and reciprocity in relation to physical attractiveness. PMID- 24214367 TI - Criteria of facial attractiveness in five populations. AB - The theory of sexual selection suggests several possible explanations for the development of standards of physical attractiveness in humans. Asymmetry and departures from average proportions may be markers of the breakdown of developmental stability. Supernormal traits may present age- and sex-typical features in exaggerated form. Evidence from social psychology suggests that both average proportions and (in females) "neotenous" facial traits are indeed more attractive. Using facial photographs from three populations (United States, Brazil, Paraguayan Indians), rated by members of the same three populations, plus Russians and Venezuelan Indians, we show that age, average features, and (in females) feminine/neotenous features all play a role in facial attractiveness. PMID- 24214368 TI - Body shape and women's attractiveness : The critical role of waist-to-hip ratio. AB - This paper examines the role of body fat distribution as measured by waist-to-hip ratio (WHR) on the judgment of women's physical attractiveness. It presents evidence that WHR is correlated with a woman's reproductive endocrinological status and long-term health risk. Three studies were conducted to investigate whether humans have perceptual and cognitive mechanisms to utilize the WHR to infer attributes of women's health, youthfulness, attractiveness, and reproductive capacity. College-age as well as older subjects of both sexes rank female figures with normal weight and low WHR as attractive and assign to them higher reproductive capability. The study concludes that WHR is a reliable and honest signal of a woman's reproductive potential. The adaptive significance of body fat distribution and its role in mate selection is also discussed. PMID- 24214369 TI - Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain. AB - In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type-specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin-positive cells tended to organize in chain-like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein-positive cells with long radial processes as well as doublecortin positive cells are oriented in the SGZ. In both regions, doublecortin-positive cells showed characteristic morphology and were positive for polysialylated neural cell adhesion molecule, beta-III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho-histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain. PMID- 24214372 TI - Successful treatment of fulminant pulmonary embolism with extracorporeal life support and simultaneous systemic thrombolytic therapy after 1 h of cardiopulmonary resuscitation. AB - Here we describe a patient with a fulminant pulmonary embolism, who has been successfully treated with an extracorporeal life support system and simultaneous systemic thrombolytic therapy after 1 h of cardiopulmonary resuscitation. PMID- 24214371 TI - Modeling thrombin generation: plasma composition based approach. AB - Thrombin has multiple functions in blood coagulation and its regulation is central to maintaining the balance between hemorrhage and thrombosis. Empirical and computational methods that capture thrombin generation can provide advancements to current clinical screening of the hemostatic balance at the level of the individual. In any individual, procoagulant and anticoagulant factor levels together act to generate a unique coagulation phenotype (net balance) that is reflective of the sum of its developmental, environmental, genetic, nutritional and pharmacological influences. Defining such thrombin phenotypes may provide a means to track disease progression pre-crisis. In this review we briefly describe thrombin function, methods for assessing thrombin dynamics as a phenotypic marker, computationally derived thrombin phenotypes versus determined clinical phenotypes, the boundaries of normal range thrombin generation using plasma composition based approaches and the feasibility of these approaches for predicting risk. PMID- 24214373 TI - The effect of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease. AB - The present study aimed to evaluate the impact of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in the Chinese Han patients with coronary heart disease (CHD). Twenty male patients of CHD with different CYP3A4*1G genotypes were orally administered a single 20 mg dose of atorvastatin. Plasma concentrations of atorvastatin and 2-hydroxyatorvastatin were measured by high performance liquid chromatography tandem mass spectrometry. The mean area under the plasma concentration-time curve from 0 to infinity (AUC0-infinity ) of atorvastatin in subjects with the CYP3A4*1G/*1G genotype were 36% or 25% lower than in those with the wild-type or the *1/*1G genotype, respectively. The time to peak plasma concentration (Tmax ) and oral clearance of atorvastatin (CL/F) were significantly different between subjects with the CYP3A4*1G/*1G genotype and the wild-type. The AUC0-infinity for 2-hydroxyatorvastatin in subjects with the CYP3A4*1G/*1G genotype was 44% or 31% lower than in those with the wild-type or the *1/*1G genotype, respectively. The peak plasma concentration, Tmax and apparent clearance of 2-hydroxyatorvastatin (CL/Fm) were significantly different between subjects with the CYP3A4*1G/*1G genotype and the wild-type. This study indicates that the CYP3A4*1G allele is associated with the pharmacokinetics of atorvastatin and its metabolites in those Chinese Han patients with CHD after a single oral dose. PMID- 24214374 TI - The effect of dietary lecithin and lipase, as a function of age, on n-9 fatty acid incorporation in the tissue lipids of Sparus aurata larvae. AB - The present study tested the effect of dietary lecithin and exogenous lipase on the incorporation of oleic acid in the tissue lipids of gilthead seabream larvae (Sparus aurata). Two of four microdiets were prepared by the addition of [(14)C]oleic acid as free fatty acid (FFA) to diets containing either 5% cuttlefish liver oil (CLO) or 5% soybean lecithin. Glycerol tri[1-(14)C]oleate was similarly incorporated in two other diets identical in lipid (4% cuttlefish liver oil, 1% soybean lecithin) and non-lipid composition but differed in that one contained a supplement of 0.05% porcine lipase. The effect of these diets was tested by following the incorporation of the label (dpm/mg larvae DBW) in the neutral and phospholipid fractions of seabream larvae at four different ages (21, 27, 32 and 45 days after hatching).A significant (p<0.05) effect of dietary lecithin on the incorporation of labelled FFA in both larval neutral and phospholipid fractions was demonstrated at all ages. This was particularly pronounced during early development (day 21) where fish fed the lecithin supplement incorporated 6.75 times more label than the diet containing [(14)C]oleic acid in CLO. The dietary lecithin enhancing effect diminished with age but was still significant at day 45 (2.17 times more label). In addition, the label was considerably higher in the phospholipid fraction compared to the neutral lipid, reflecting the high demand for membrane synthesis during rapid growth. Lecithin fed larvae demonstrated a higher consumption rate and efficiency of incorporation than fish consuming the cuttlefish liver oil diet, suggesting an emulsifying function for dietary phospholipid.In contrast, the supplementation with lipase showed a clear effect only in older fish where 45 day old larvae fed the lipase diet demonstrated a 3.42 times increase in radioactivity in their tissue lipids. This late lipase response may be the result of an insufficient level of dietary lecithin (M) and a short intestinal length being ineffective, in the early larval stages, in incorporating labelled free fatty acid from dietary glycerol tri[1-(14)C]oleate breakdown. PMID- 24214375 TI - Changes in tissue and plasma free amino acid concentrations after feeding in Atlantic cod. AB - Atlantic cod, Gadus morhua, were maintained on a diet of sandeel and after a 6 day fast were refed a single meal. Concentrations of free amino acids (AAs) were measured in hepatic portal and cardiac blood as well as in the stomach and white muscle at intervals of 6h up to 24h post-feeding. The appearance of both essential and non-essential AAs in the hepatic portal blood was significantly correlated, up to 12h after feeding, to their abundance in the diet. There was a significant decline in total AA concentration in cardiac blood after 6h, followed by a significant increase at 12h. No significant changes in total AA concentration were observed in the other tissues, although mean concentration increased at 12 or 18h. At a more detailed level, the post-prandial changes in concentration of some essential AAs were consistent with their having a role in the stimulation of protein synthesis after feeding. PMID- 24214376 TI - Influence of oral administration of estradiol-17beta and testosterone on growth, digestion, food conversion and metabolism in the underyearling red sea bream, Chrysophrys major. AB - Estradiol-17beta (E2) administered in the diet to the red sea bream Chrysophrys major did not affect appetite, food conversion efficiency, protein efficiency ratio and specific growth rate. Serum concentrations of total protein, albumin, globulin, vitellogenin, alpha-amino acids, total lipid, free fatty acids, cholesterol and calcium were elevated. The hepatosomatic index was also increased. Activities of hepatic enzymes including lactate dehydrogenase, isocitrate dehydrogenase and glutamate-pyruvate transaminase were higher than found in untreated control fish. Intestinal activity of leucine aminopeptidase was augmented. However, there were no changes in muscle water, protein, lipid and glycogen content. In contrast, testosterone (T) given by the same route increased appetite, food conversion efficiency, protein efficiency ratio and specific growth rate. There were no alterations in serum protein and calcium concentrations but serum glucose, ammonia and triglyceride levels were elevated. Hepatic glycogen content was increased. The activities of hepatic fructose- 1,6 diphosphatase, glucose-6-phosphatase and glycogen synthetase and intestinal activities of alkaline phosphatase and tau-glutamyltransferase were higher than noted on control fish. The results reveal that estradiol-17beta and testosterone exerted different metabolic effects in the red sea bream and they suggest that testosterone exerts its anabolic actions by increasing appetite, food conversion efficiency and activities of digestive enzymes. PMID- 24214377 TI - Steroidogenesis by ovaries and testes of the European catfish, the wels (Silurus glanis), in vitro. AB - Testosterone, 3alpha,17-dihydroxy-5beta-pregnen-20-one, 17,20beta-dihydroxy-4 pregnen-3-one (17,20betaP) and 5beta-pregnane-3alpha,17,20beta-triol were identified as the major metabolites of [(3)H] 17-hydroxyprogesterone in ovarian incubations of the European catfish Silurus glanis. 17,20betaP and the reduced triol were present only in ovaries from fish primed with carp hypophysial homogenate (chh) while testosterone yields were significantly higher in controls than in treated fish. 11-Ketotestosterone, 11beta-hydroxytestosterone and 17,20alpha-dihydroxy-4-pregnen-3-one (17,20alphaP) were identified as the major metabolites of [(3)H]17-hydroxyprogesterone in in vitro incubations of testes of a spermiating catfish. There was no significant production of conjugates or other water soluble metabolites by either sex. The stimulation of plasma 17,20alphaP, 17,20betaP and 11beta-hydroxytestosterone by chh in primed but not control males suggests that the role of these steroids in spermiation should be further examined. PMID- 24214378 TI - Influence of gonadotropic hormone-releasing hormone analog (GnRH-A) on plasma sex steroid profiles and milt production in male winter flounder, Pseudopleuronectes americanus (Walbaum). AB - The effects of gonadotropic hormone-releasing hormone analog (GnRH-A) treatment on the onset and duration of increases in plasma sex steroids and milt production (milt volume and number of spermatozoa) were investigated in prespawning male winter flounder. After treatment of maturing males during the winter with a single injection of either 20 or 200 MUg/kg [D-Ala(6), Pro(9)-NHEt]LHRH (GnRH-A), plasma levels of testosterone and 11-ketotestosterone were increased within 12h and the steroid hormone levels remained elevated for long periods lasting several days. The androgenic steroid response of males was delayed after the administration of a lower dose of GnRH-A (2 MUg/kg). Although a single GnRH-A injection in December or January advanced the onset of spermiation in some males, only small amounts (<50 MUl) of milt could be collected. By March, all males were in spermiating condition following GnRH-A treatment; however, significant increases in sperm production, particularly increases in milt volume, occurred in fish twice treated with GnRH-A. PMID- 24214379 TI - Purification of gonadotropins (PmGTH I and II) from red seabream (Pagrus major) and development of a homologous radioimmunoassay for PmGTH II. AB - Two gonadotropic glycoproteins (PmGTH I and II) were purified by ion-exchange chromatography, gel filtration and preparative SDS-PAGE, from pituitaries of red seabream, a marine teleost which has an asynchronous-type ovary and spawns almost daily during the spawning season. The glycoproteins were composed of distinct subunits and the molecular weights were estimated to be 32 and 38 kDa for PmGTH I and PmGTH II, respectively. Both PmGTH I and II were active in two homologous bioassays: in vitro oocyte maturation and/or in vitro estradiol-17beta production assays. These two GTHs were distinct in electrostatic properties, molecular weight, stability and yields from pituitaries during the spawning season. These properties suggest that PmGTH I and II correspond to salmon GTH I and II, respectively.A homologous radioimmunoassay with which to measure PmGTH II was developed using a rabbit antiserum against the beta subunit of PmGTH II and intact PmGTH II as standards and radioactive competitors. Competition curves for red seabream plasma and pituitary extract were parallel to the standard curve, while PmGTH I had low cross-reactivity (3.1 %) with the antibody. This specific RIA system showed an in vivo LHRHa induced GTH surge in the plasma of female red seabream. PMID- 24214380 TI - Stimulation of acetylcholinesterase activity by triiodothyronine in the brain of Singi fish, Heteropneustes fossilis (Bloch). AB - Three consecutive days of injections of triiodothyronine (T3)(0.038, 0.075, 0.15 and 1.54 nmoles/g) significantly elevated the acetylcholinesterase (AchE) activity in the brain of Singi fish, Heteropneustes fossilis (Bloch). The higher doses of 0.075, 0.15 and 1.54 nmoles of T3/g induced a greater increase in enzyme activity than 0.038 nmoles/g. A T3 dose of 0.019 nmoles/g was found to be ineffective. The T3 action on AchE activity was blocked by cycloheximide. Thiourea treatment for 30 days decreased the AchE activity below the control level. This reduced level of the enzyme activity was brought back even above the control level by T3 injections. It is, therefore, suggested that thyroid hormone is involved in the sustenance of AchE activity in fish brain. PMID- 24214381 TI - Annual cyclic, and castration and cyproterone acetate-induced, changes in sialic acid content of the seminal vesicle of the catfish, Heteropneustes fossilis (Bloch). AB - In this study, the presence of sialic acid is demonstrated in the seminal vesicle (SV) of Heteropneustes fossilis. Sialic acid levels show an annual variation that was correlated with the secretory activity of the SV (expressed as the SV somatic index (SV-SI)) with the index being lowest in resting phase (January) and highest in spawning phase (July). Sialic acid was not detectable from November to March (resting to mid-preparatory phases). Castration (3 weeks) induced a significant rise in both SV-SI and SV sialic acid content possibly due to an elevated local production of androgens under the influence of increased gonadotropin secretion. Cyproterone acetate treatment caused a significant decrease in both SV-SI and SV sialic acid content. The results suggest that secretion of sialic acid in the SV is influenced by androgens and its measurement can be used as a simple and reliable index for quantitative assessment of the functional testicular state. PMID- 24214382 TI - Comparison of 3,5,3'-triiodo-L-thyronine and L-thyroxine absorption from the intestinal lumen of the fasted rainbow trout, Oncorhynchus mykiss. AB - The absorptions of 3,5,3'-triiodo-L-thyronine (T3) and L-thyroxine (T4) from the intestinal lumen of the rainbow trout were compared in vivo. Tracer doses of [(125)I]T4 ((+)T4) or [(125)I]T3 ((*)T3) were injected through an anal cannula into the duodenum of trout fasted for 3 days at 12 degrees C, and radioactivity was measured in blood and tissues at 4-48 h. (*)T3 was removed more extensively than (*)T4 from the intestinal lumen and more radioactivity was absorbed into the blood and tissues of u+T3-injected trout than (*)T4-injected trout. HPLC analysis showed that a high proportion of the radioactivity in the plasma, liver, kidney and intestinal lumen of (*)T3-injected trout remained as the parent (*)T3. However, in (*)T4-injected trout most plasma radioactivity was in the form of (125)I(-), and by 24 h a high proportion of luminal radioactivity was (125)I(-). By 48 h, over 4% of the injected (*)T3 and 1% of the injected (*)T4 dose resided in the gall bladder, primarily as derivatives of (*)T3 or (*)T4. We conclude that T3 is absorbed more effectively than T4 from the intestinal lumen of fasted trout, indicating the potential for an enterohepatic T3 cycle. PMID- 24214383 TI - B2S2O9: a boron sulfate with phyllosilicate topology. PMID- 24214384 TI - Neanderthal hand and foot remains from Moula-Guercy, Ardeche, France. AB - The hand and foot remains from Moula-Guercy cave (Ardeche, France) comprise 24 specimens of Eemian age (ca. 120 ka). The specimens include primarily complete elements, which are rare among the Moula-Guercy postcrania. The hand remains have several characteristic Neanderthal traits including a laterally facing (parasagittally oriented) second metacarpal-capitate articulation, a short styloid process, a wide proximal articular surface on the third metacarpal, and absolutely expanded apical tuberosities on the distal hand phalanges relative to modern humans. The foot remains include several incomplete elements along with an antimeric pair of naviculars, a medial cuneiform and cuboid, and a single complete element from each of the distal segments (one each: metatarsal, proximal foot phalanx, intermediate foot phalanx, distal foot phalanx). Consistent among the specimens are relatively wide diaphyses for length in the metatarsals and phalanges and large and prominent muscle attachments, both consistent with previously published Neanderthal morphology. The hand and foot collection from Moula-Guercy is an important dataset for future studies of Neanderthal functional morphology, dexterity, and behavior as it represents a previously undersampled time period for European Neanderthals. PMID- 24214385 TI - Neanderthal axial and appendicular remains from Moula-Guercy, Ardeche, France. AB - Excavations carried out during the 1990s at Moula-Guercy cave Ardeche, France, yielded 108 hominid specimens dating to 100-120 Ka. In this paper, we describe and compare the 39 axial and appendicular specimens not including hand and foot bones. Among these remains are a large adult femur, several clavicles, a likely antimeric pair of radial heads, and a nearly complete superior pubic ramus. Analyses of this material indicate a clear affinity with Neanderthals by the presence of large and robust muscle attachments, thick long bone cortices, a long pubic ramus, and a superoinferiorly flattened clavicle shaft. The recovered remains reveal the presence of a mature male, a smaller mature individual, possibly a reproductive age female, an immature individual of age 10-12, and a second immature individual of age 4. Future analyses on the Moula-Guercy remains will illuminate ties to other known Neanderthal populations and contribute to the ongoing debate over the relative rate of Neanderthal metric growth. PMID- 24214387 TI - Design and calibration of an electrostatic energy analyzer-time-of-flight mass spectrometer for measurement of laser-desorbed ion kinetic energies. AB - The design of a hybrid electrostatic energy analyzer-time-of-flight mass spectrometer for measurement of ion kinetic energies produced by laser desorption ionization is presented. The need for experimental evaluation of the calibration and performance of the instrument is discussed and a novel laser multiphoton ionization technique, which allows experimental calibration of the energy bandpass of the electrostatic energy analyzer, is described. Laser multiphoton ionization at varying electric field strengths also allows the effects of electric field distortions on energy resolution of the instrument to be probed. Measurement of the translational energies of ions produced by 266-nm laser desorption ionization at 48 mJ/cm(2) of material adsorbed to a stainless steel probe by using this instrument also is presented. Ion translational energies of +19+/-5, +10+/-5, and +10+/-5 eV are found for adsorbed Na(+), K(+), and m-xylene M(+), respectively. PMID- 24214388 TI - Evaluation of steric and substituent effects in phenols by competitive reactions of dimethyl ether ions in a quadrupole ion trap. AB - Competitive reactions of dimethyl ether ions are used to probe the steric and substituent effects of substituted phenols and anisoles in a quadrupole ion trap. The relative percentages of protonation and methylene substitution from the reactions of dimethyl ether ions show a correlation with size, location, and number of subsrituents on the aromatic ring. Although gas-phase basicity measurements of the phenols show no discernible correlation with the percentages of competitive reactions, semiempirical calculations show a good correlation between the trend in heats of formation and the trend in methylene substitution percentage. Reactions with deuterated compounds show that the methylene substitution reaction occurs on the ring. PMID- 24214386 TI - Trans-thylakoid ?pH dependent oscillation of F(PSI)/F(PSII) under continuous irradiance in isolated thylakoids. AB - Energy distribution between photosystems (PSI & PSII) under prolonged and continuous white light irradiance was assessed by monitoring the progress of their fluorescence emission (FPSI/FPSII) at 77 K. Our observations indicate FPSI/FPSII to oscillate with the progress of irradiance treatments at all intensities tested (100, 200, 500, and 800 MUE m(-2) S(-1)). The amplitude of the oscillation increased with the progress, whereas the periodicity of the oscillation increased with the intensity of the incident irradiance. Spectral analysis indicated fluctuation of FPSI to be the major determinant of the observed oscillation. The first rise and fall of FPSI/FPSII overlapped with phosphorylation and dephosphorylation of LHCII, but oscillation of FPSI/FPSII continued for several cycles without any further phosphorylation of LHCII. Moreover, in presence of DCMU where linear electron flow (LEF) is suppressed and LHCII phosphorylation is completely abolished, the oscillation of FPSI/FPSII was not abolished. These data indicated that LHCII phosphorylation was not essential for the observed oscillation of energy distribution between the photosystems. In contrast, in the presence of inhibitors of cyclic electron flow (CEF) like Antimycin A (AA) and rotenone, the oscillation of FPSI/FPSII was either abolished or severely dampened. Additionally, the oscillation was also abolished in presence of uncouplers like NH4Cl and nigericin that cancels the trans-thylakoid ?pH. Thus, trans-thylakoid ?pH, generated through CEF, appear to be an important determinant of oscillation of FPSI/FPSII in isolated thylakoids. The phenomenon of oscillation could be associated with a CEF mediated chromatic adaptation of PSI in presence of excess irradiance. PMID- 24214389 TI - Neighboring group participation in the electrospray ionization tandem mass spectra of polyamine toxins of spiders. Part 1: alpha, omega-diaminoalkane compounds. AB - The fragmentation pattern of N-(4-aminobutyl)-3-(4-hydroxyphenyl)prop-2-enamide (1) is characterized by an ion formed by neighboring group participation. The phenolic hydrogen is transferred to the primary amino group via a 15-membered ring. This has been proven by H/D exchange reactions and by analyzing homologues and derivatives. PMID- 24214390 TI - Characterization of disulfide linkages and disulfide bond scrambling in recombinant human macrophage colony stimulating factor by fast-atom bombardment mass spectrometry of enzymatic digests. AB - Fast-atom bombardment mass spectrometry was used to study disulfide bonding patterns in heat-denatured human recombinant macrophage colony stimulating factor (rhM-CSF). The heat-denaturated protein was studied by analysis of the pattern of peptides in the proteolytic digests. Native rhM-CSF is a homodimer with intramolecular disulfide linkages between Cys7-Cys90, Cys48-Cys139, and Cys102 Cys146 and intermolecular linkages between Cys31-Cys31, and the pairs Cys157 and Cys159. Brief heating for 1 min leads to partial disulfide bond scrambling. In addition to the native disulfide bonds between Cys7-Cys90, Cys48-Cys139, and Cys31-Cys31, nonnative disulfide bonds were detected between Cys48-Cys90 and Cys48-Cys102. When heated for 5 min the disulfide bonds of rhM-CSF are completely scrambled and lead to nonnative intramolecular disulfide bonds between Cys48 Cys102 and Cys90-Cys102 and one intermolecular disulfide bond between Cys102 Cys102. PMID- 24214391 TI - Chemical substructure identification by mass spectral library searching. AB - A library-search procedure that identifies structural features of an unknown compound from its electron-ionization mass spectrum is described. Like other methods, this procedure first retrieves library compounds whose spectra are most similar to the spectrum of an unknown compound. It then deduces structural features of the unknown compound from the chemical structures of the retrievals. Unlike other methods, the significance of each retrieved spectrum is weighted according to its similarity to the spectrum of the unknown compound. Also, a "peaks-in-common" screening step serves to reduce search times and an optimized dot product function provides the match factor. If the molecular weight of the unknown compound is provided, the identification of certain substructures can be improved by including "neutral loss" peaks. Correlations between the presence of a substructure in a test compound and its presence among library retrievals were derived from the results of searching the NIST/EPA/NIH reference library with a 7891 compound test set. These correlations allow the estimation of probabilities of substructure occurrence and absence in an unknown compound from the results of a library search. This method may be viewed as an optimization of the "K-nearest neighbor" method of Isenhour and co-workers, with improvements that arise from spectrum screening, peak scaling, an optimal distance measure, a relative distance weighting scheme, and a larger reference library. PMID- 24214392 TI - Comparative study of different thermospray interfaces with carbamate pesticides: Influence of the ion source geometry. AB - Sixteen carbamate pesticides that belong to four chemical classes (oxime-N methylcarbamates, aryl N-methylcarbamates, N-phenylcarbamates, and methyl esters of substituted carbamic acids) were investigated via three different commercially available thermospray interfaces and ion sources that exhibit wide differences in source geometry. Comparisons were made between the three interfaces with respect to ion formation and sensitivity of detection. Experimental parameters were standardized to obtain comparable experimental conditions. Very similar mass spectra for most carbamates were obtained that illustrate independence from the geometry of the ionization and desolvation chambers of the interfaces. These findings are in sharp contrast to several literature reports. However, thermally labile carbamates gave unsatisfactory results with regard to spectral compatibility between the interfaces. Such differences were due to thermally assisted hydrolysis reactions that occur in the vaporizer probe prior to ionization and reflect differences in the vaporizer designs. The study proves conclusively that comparable spectra can be obtained under thermospray with different interfaces and mass spectrometers. PMID- 24214394 TI - Discovery of recurrent structural variants in nasopharyngeal carcinoma. AB - We present the discovery of genes recurrently involved in structural variation in nasopharyngeal carcinoma (NPC) and the identification of a novel type of somatic structural variant. We identified the variants with high complexity mate-pair libraries and a novel computational algorithm specifically designed for tumor normal comparisons, SMASH. SMASH combines signals from split reads and mate-pair discordance to detect somatic structural variants. We demonstrate a >90% validation rate and a breakpoint reconstruction accuracy of 3 bp by Sanger sequencing. Our approach identified three in-frame gene fusions (YAP1-MAML2, PTPLB-RSRC1, and SP3-PTK2) that had strong levels of expression in corresponding NPC tissues. We found two cases of a novel type of structural variant, which we call "coupled inversion," one of which produced the YAP1-MAML2 fusion. To investigate whether the identified fusion genes are recurrent, we performed fluorescent in situ hybridization (FISH) to screen 196 independent NPC cases. We observed recurrent rearrangements of MAML2 (three cases), PTK2 (six cases), and SP3 (two cases), corresponding to a combined rate of structural variation recurrence of 6% among tested NPC tissues. PMID- 24214396 TI - Formation of virions is strictly required for turnip yellows virus long-distance movement in plants. AB - Viral genomic RNA of the Turnip yellows virus (TuYV; genus Polerovirus; family Luteoviridae) is protected in virions formed by the major capsid protein (CP) and the minor component, the readthrough (RT*) protein. Long-distance transport, used commonly by viruses to systemically infect host plants, occurs in phloem sieve elements and two viral forms of transport have been described: virions and ribonucleoprotein (RNP) complexes. With regard to poleroviruses, virions have always been presumed to be the long-distance transport form, but the potential role of RNP complexes has not been investigated. Here, we examined the requirement of virions for polerovirus systemic movement by analysing CP-targeted mutants that were unable to form viral particles. We confirmed that TuYV mutants that cannot encapsidate into virions are not able to reach systemic leaves. To completely discard the possibility that the introduced mutations in CP simply blocked the formation or the movement of RNP complexes, we tested in trans complementation of TuYV CP mutants by providing WT CP expressed in transgenic plants. WT CP was able to facilitate systemic movement of TuYV CP mutants and this observation was always correlated with the formation of virions. This demonstrated clearly that virus particles are essential for polerovirus systemic movement. PMID- 24214395 TI - P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis. AB - Retinal rod photoreceptor cells have double membrane discs located in their outer segments (ROS) that are continuously formed proximally from connecting cilia (CC) and phagocytized distally by the retinal pigmented epithelium. The major component of these rod discs, the light-sensitive visual pigment rhodopsin (Rho), consists of an opsin protein linked to 11-cis-retinal. The P23H mutation of rod opsin (P23H opsin) is the most common cause of human blinding autosomal dominant retinitis pigmentosa (adRP). A mouse model of adRP with this mutation (Rho(P23H/+)) shows low levels of P23H opsin protein, partial misalignment of discs and progressive retinal degeneration. However, the impact of mutant P23H opsin on the formation of abnormal discs is unclear and it is still unknown whether this mutant pigment can mediate phototransduction. Using transretinal ERG recordings, we demonstrate that P23H mutant Rho can trigger phototransduction but Rho(P23H/P23H) rods are ~17 000-fold less sensitive to light than Rho(+/+) rods and produce abnormally fast photo-responses. By analyzing homozygous Rho(P23H/P23H) knock-in mice, we show that P23H opsin is transported to ciliary protrusions where it forms sagittally elongated discs. Transmission electron microscopy of postnatal day (PND) 14 Rho(P23H/+) mouse retina revealed disordered sagittally oriented discs before the onset of retinal degeneration. Surprisingly, we also observed smaller, immature sagittally oriented discs in PND14 Rho(+/)(-) and Rho(+/+) mice that were not seen in older animals. These findings provide fundamental insights into the pathogenesis of the P23H mutant opsin and reveal a novel early sagittally aligned disc formation step in normal ROS disc expansion. PMID- 24214397 TI - Arabidopsis 56-amino acid serine palmitoyltransferase-interacting proteins stimulate sphingolipid synthesis, are essential, and affect mycotoxin sensitivity. AB - Maintenance of sphingolipid homeostasis is critical for cell growth and programmed cell death (PCD). Serine palmitoyltransferase (SPT), composed of LCB1 and LCB2 subunits, catalyzes the primary regulatory point for sphingolipid synthesis. Small subunits of SPT (ssSPT) that strongly stimulate SPT activity have been identified in mammals, but the role of ssSPT in eukaryotic cells is unclear. Candidate Arabidopsis thaliana ssSPTs, ssSPTa and ssSPTb, were identified and characterized. Expression of these 56-amino acid polypeptides in a Saccharomyces cerevisiae SPT null mutant stimulated SPT activity from the Arabidopsis LCB1/LCB2 heterodimer by >100-fold through physical interaction with LCB1/LCB2. ssSPTa transcripts were more enriched in all organs and >400-fold more abundant in pollen than ssSPTb transcripts. Accordingly, homozygous ssSPTa T-DNA mutants were not recoverable, and 50% nonviable pollen was detected in heterozygous ssspta mutants. Pollen viability was recovered by expression of wild type ssSPTa or ssSPTb under control of the ssSPTa promoter, indicating ssSPTa and ssSPTb functional redundancy. SPT activity and sensitivity to the PCD-inducing mycotoxin fumonisin B1 (FB1) were increased by ssSPTa overexpression. Conversely, SPT activity and FB1 sensitivity were reduced in ssSPTa RNA interference lines. These results demonstrate that ssSPTs are essential for male gametophytes, are important for FB1 sensitivity, and limit sphingolipid synthesis in planta. PMID- 24214398 TI - A gamma-glutamyl cyclotransferase protects Arabidopsis plants from heavy metal toxicity by recycling glutamate to maintain glutathione homeostasis. AB - Plants detoxify toxic metals through a GSH-dependent pathway. GSH homeostasis is maintained by the gamma-glutamyl cycle, which involves GSH synthesis and degradation and the recycling of component amino acids. The enzyme gamma-glutamyl cyclotransferase (GGCT) is involved in Glu recycling, but the gene(s) encoding GGCT has not been identified in plants. Here, we report that an Arabidopsis thaliana protein with a cation transport regulator-like domain, hereafter referred to as GGCT2;1, functions as gamma-glutamyl cyclotransferase. Heterologous expression of GGCT2;1 in Saccharomyces cerevisiae produced phenotypes that were consistent with decreased GSH content attributable to either GSH degradation or the diversion of gamma-glutamyl peptides to produce 5 oxoproline (5-OP). 5-OP levels were further increased by the addition of arsenite and GSH to the medium, indicating that GGCT2;1 participates in the cellular response to arsenic (As) via GSH degradation. Recombinant GGCT2;1 converted both GSH and gamma-glutamyl Ala to 5-OP in vitro. GGCT2;1 transcripts were upregulated in As-treated Arabidopsis, and ggct2;1 knockout mutants were more tolerant to As and cadmium than the wild type. Overexpression of GGCT2;1 in Arabidopsis resulted in the accumulation of 5-OP. Under As toxicity, the overexpression lines showed minimal changes in de novo Glu synthesis, while the ggct2;1 mutant increased nitrogen assimilation by severalfold, resulting in a very low As/N ratio in tissue. Thus, our results suggest that GGCT2;1 ensures sufficient GSH turnover during abiotic stress by recycling Glu. PMID- 24214399 TI - FOXP1 mutations cause intellectual disability and a recognizable phenotype. AB - Mutations in FOXP1, located at 3p13, have been reported in patients with global developmental delay (GDD), intellectual disability (ID), and speech defects. Mutations in FOXP2, located at 7q31, are well known to cause developmental speech and language disorders, particularly developmental verbal dyspraxia (DVD). FOXP2 has been shown to work co-operatively with FOXP1 in mouse development. An overlap in FOXP1 and FOXP2 expression, both in the songbird and human fetal brain, has suggested that FOXP1 may also have a role in speech and language disorders. We report on a male child with a 0.19 MB intragenic deletion that is predicted to result in haploinsufficiency of FOXP1. Review of our patient and others reported in the literature reveals an emerging phenotype of GDD/ID with moderate to severe speech delay where expressive speech is most severely affected. DVD appears not to be a distinct feature in this group. Facial features include a broad forehead, downslanting palpebral fissures, a short nose with broad tip, relative or true macrocephaly, a frontal hair upsweep and prominent digit pads. Autistic traits and other behavioral problems are likely to be associated with haploinsufficiency of FOXP1. Congenital malformations may be associated. PMID- 24214400 TI - Birth management and perinatal care : Biosocial perspectives. AB - In the past four decades, obstetric and neonatal care practices have changed dramatically throughout the western world. As a result, humans now confront unprecedented situations for which they have no biological preparation or cultural experience. In these special issues, an integrated view of the evolving practices of birthing and infant care are discussed from a variety of perspectives. Contributors attempt to show how understanding of the biomedical and psychosocial issues can be informed by cross-cultural and cross-species evidence concerning birth management, neonatal care, and early development. The individual contributions are summarized in this introductory article. PMID- 24214401 TI - Historical perspectives on parental investment and childbearing. AB - This article provides some historical perspectives on parental investment and childbearing. Scholars are debating whether parents always loved and nurtured their children. The historical record provides some support for both sides. Parents who abandoned their children often did so with the hope that someone else would be able to raise them. But others, like the ancient Carthagians, sacrificed their own children to appease the gods. Colonial Americans appear to have been particularly solicitous of the well-being of their children. The paper then traces the changes in the role of women in facilitating the process of childbirth in America. Scholars are cautioned not to idealize the childbirth experiences of women in the past as they experienced considerable pain and fear. PMID- 24214402 TI - The evolutionary history of childbirth : Biology and cultural practices. AB - Consideration of the evolutionary and cross-cultural history of childbirth reveals many differences between the ways in which most human females have experienced childbirth and the ways in which most women in contemporary industrialized obstetric settings experience the event. In this paper I review two of these differences: the pain and anxiety of labor and delivery and the discontinuity of care provided for the mother and infant. I argue that much of the dissatisfaction with birth practices in the United States results from the failure of modern obstetric practice to meet the evolved needs of mothers and infants. PMID- 24214403 TI - Oxytocin and the augmentation of labor : Human and medical perspectives. AB - At least a third of the women giving birth in the United States receive intravenous oxytocin for the induction and augmentation of labor. The problem of inactive or ineffective labor remains a major challenge for birth attendants, midwives, and physicians who practice obstetrics. Before the discovery of oxytocin, traditional approaches to augmentation ranged from magical and folk interventions to extensive bloodletting. Despite its wide use the effectiveness of oxytocin augmentation has not been well studied, and current research raises new questions about its effect on the brain. PMID- 24214404 TI - Two trends in middle-class birth in the United States. AB - This discussion focuses on two important trends in American childbirth that have emerged in the past 30 years, the demand for a perfect baby and the desire for a perfect birth. These two trends are particularly important in the subgroup of middle-class women who have decided on delayed childbearing. Tremendous technological innovations, such as ultra-sound, prenatal genetic analysis, and fetal monitoring, have promoted the perception that physicians can control the prenatal environment and predict the pregnancy outcome. This expectation may lead to bitterness and anger in the event of an adverse pregnancy outcome. In contrast, women and their families have also come to desire more control over the birth experience. If the parents' birth plan is not achieved and their expectations not fulfilled, many parents feel they have not performed well. When the physician acts as a guide in the birth process, parents and physicians together may transcend the conflict to achieve a more satisfactory birth experience. PMID- 24214405 TI - Defining reducible risk : Social dimensions of assessing birth technologies. AB - In maternity care, costly high-technology interventions that have never been shown to be clinically effective continue to be used in the United States, while inexpensive and effective low-technology interventions continue to be underused. Three high-technology approaches to risk reduction-electronic fetal monitoring, cesarean section, and home uterine activity monitoring are contrasted with three low-technology approaches-prenatal care, smoking cessation, and nutrition supplementation. These technologies are examined in terms of current controversies over their safety, efficacy, and cost-effectiveness. Examination of these controversies illustrates how the medical technology industry, the regulatory process, and systems of social stratification contribute to social and cultural constructions of what are regarded as reducible birth risks. PMID- 24214406 TI - Photodynamic diagnosis using 5-aminolevulinic acid during gastrectomy for gastric cancer. AB - BACKGROUND AND OBJECTIVES: Five-aminolevulinic acid (ALA) has received much attention recently as a new-generation photosensitive substance for photodynamic diagnosis (PDD). This study aimed to investigate the feasibility of intraoperative PDD using ALA to identify gastric cancer. METHODS: Intraoperative PDD was carried out in 26 lesions of 21 patients with gastric cancer. Before surgery, 1.0 g of ALA solution was given orally through a stomach tube. After tumor resection, resected specimens were investigated by an endoscopic PDD system, and red fluorescence-positive lesions were compared with the pathological result. RESULTS: Red fluorescence was detected in 15 lesions of 11 patients. The sensitivity, specificity, and accuracy of PDD using ALA in detecting gastric cancer were 57.7, 100, and 66.7%, respectively. The incidence of laparoscopic surgery was significantly lower in the PDD-positive group than in PDD-negative cases (18.2% vs. 60.0%; P = 0.049), while that of intestinal type tumor was significantly higher in PDD-positive compared to PDD-negative patients (93.3% vs. 27.3%; P < 0.001). CONCLUSIONS: Fluorescence navigation by PDD provides good visualization and detection of gastric cancer lesions, and might be particularly useful for intestinal type gastric cancer. Thus, PDD using ALA seems to be a promising diagnostic tool for gastric cancer. PMID- 24214407 TI - Intuitive, but not simple: including explicit water molecules in protein-protein docking simulations improves model quality. AB - Characterizing the nature of interaction between proteins that have not been experimentally cocrystallized requires a computational docking approach that can successfully predict the spatial conformation adopted in the complex. In this work, the Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high-resolution crystallographically characterized "dry" protein-protein complexes and was shown to reliably identify native-like models. However, most current protein-protein docking algorithms fail to explicitly account for water molecules involved in bridging interactions that mediate and stabilize the association of the protein partners, so we used HINT to illuminate the physical and chemical properties of bridging waters and account for their energetic stabilizing contributions. The HINT water Relevance metric identified the "truly" bridging waters at the 30 protein-protein interfaces and we utilized them in "solvated" docking by manually inserting them into the input files for the rigid body ZDOCK program. By accounting for these interfacial waters, a statistically significant improvement of ~24% in the average hit-count within the top-10 predictions the protein-protein dataset was seen, compared to standard "dry" docking. The results also show scoring improvement, with medium and high accuracy models ranking much better than incorrect ones. These improvements can be attributed to the physical presence of water molecules that alter surface properties and better represent native shape and hydropathic complementarity between interacting partners, with concomitantly more accurate native-like structure predictions. PMID- 24214408 TI - Use of electrochemotherapy in a case of neck skin metastasis of oral squamous cell carcinoma: case report and considerations. AB - BACKGROUND: Squamous cell carcinoma (SCC) is the most common oral cavity malignant tumor. Surgery, radiotherapy, and chemotherapy have been the major options for its treatment. Electrochemotherapy (ECT) is a novel local treatment successfully used in secondary or primary skin or subcutaneous tumors. This new cancer treatment is a modality in which a locally applied electrical field enhances cell membrane permeability, thereby allowing greater intracellular accumulation of a chemotherapeutic agent. METHODS: We report a case of a man affected by an ulcerated SCC. The man was treated with ECT with good results. RESULTS: In our case, ECT was successful in the management of extensive metastasis of SCC in clinical conditions, whereas other approaches were rejected. CONCLUSION: This case shows good clinical results; however, other studies are necessary to show that ECT should be considered as a promising treatment option. PMID- 24214410 TI - CYP3A5*3 and bilirubin predict midazolam population pharmacokinetics in Asian cancer patients. AB - We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach. Pharmacokinetic data were obtained from 24 adult cancer patients who received an intravenous bolus dose of 1 mg MDZ as a CYP3A phenotyping probe, 1-day before starting FOLFIRI chemotherapy. Concentrations of MDZ and its major metabolites, 1'-hydroxymidazolam (1OHM) and 1'-hydroxymidazolam glucuronide (HMG) were measured using liquid chromatography/mass spectrometry. The population pharmacokinetic study was conducted using NONMEM. Demographics, clinical characteristics, and genetic polymorphisms were screened as covariates. A two compartment model for MDZ and two sequential compartments representing 1OHM and HMG best described the data. The CYP3A5*3 and total bilirubin level significantly influenced MDZ clearance. The population typical MDZ clearance for CYP3A5*3 expressers was 22% lower than non-expressers. Baseline bodyweight was a statistically significant covariate for clearance and distribution volume of 1OHM. Creatinine clearance was positively correlated with HMG clearance. Our data indicate that CYP3A5*3, total bilirubin, bodyweight, and creatinine clearance are important predictors of MDZ and metabolite pharmacokinetics. Further studies in more patients are needed to explore the links between the identified covariates and the disposition of MDZ and its metabolites. PMID- 24214409 TI - Developing an international Pseudomonas aeruginosa reference panel. AB - Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis (CF) patients and causes a wide range of infections among other susceptible populations. Its inherent resistance to many antimicrobials also makes it difficult to treat infections with this pathogen. Recent evidence has highlighted the diversity of this species, yet despite this, the majority of studies on virulence and pathogenesis focus on a small number of strains. There is a pressing need for a P. aeruginosa reference panel to harmonize and coordinate the collective efforts of the P. aeruginosa research community. We have collated a panel of 43 P. aeruginosa strains that reflects the organism's diversity. In addition to the commonly studied clones, this panel includes transmissible strains, sequential CF isolates, strains with specific virulence characteristics, and strains that represent serotype, genotype or geographic diversity. This focussed panel of P. aeruginosa isolates will help accelerate and consolidate the discovery of virulence determinants, improve our understanding of the pathogenesis of infections caused by this pathogen, and provide the community with a valuable resource for the testing of novel therapeutic agents. PMID- 24214412 TI - Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy. AB - Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and alpha-smooth muscle actin (alphaSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and alphaSMA antibodies were performed on paraffin-embedded tissue. Fisher's exact test was performed to test the association between FAP and alphaSMA expression and disease status. Kaplan-Meier method with log-rank test was used to check the survival difference between different FAP tumor/stroma expressions. FAP stroma (pos) . expression was strongly associated with higher recurrences rate [OR: 15.95; 95 % CI: 1.521-835.206; p = 0.0072]. Cases with combined FAP stroma (pos) and FAP tumor (neg) had higher death rate [OR: 4.845; 95 % CI: 1.53-16.61; p = 0.0046] and higher recurrence rate [OR: 5.12; 95 % CI: 0.91-54.42; p = 0.0487] compared to all the others. Cases with combined FAP stroma (neg) and FAP tumor (neg) were more likely to have lower recurrence rates [OR: 0.086; 95 % CI: 0.001-0.997; p = 0.0248]. alphaSMA was expressed by tumor-associated stroma in 95 % of cases and by tumor cells in 9 % of cases. No statistical power was found for alphaSMA and disease status. Our data indicate that FAP plays an important role in predicting tumor aggressiveness in patients with EOC post-neoadjuvant therapy, and its frequent expression in this malignancy implicates that FAP targeted therapy could be a very attractive strategy. PMID- 24214413 TI - Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study. AB - CONTEXT: Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met. OBJECTIVE: This study aims to perform a patient centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer. DESIGN, SETTING, AND PATIENTS: Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned. MAIN OUTCOME MEASURES: (1) Physical symptoms--assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care--identifying whether diagnostic tests for prostate cancer (prostate specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the "watchful waiting" paradigm for prostate cancer surveillance. (3) Informational needs--assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out information and what factors guide which primary information source a survivor would use. RESULTS: Median duration between prostate cancer diagnosis and survey response was 9 years. Of the study population, 80 % was diagnosed at an early stage. Survivors had reported significant problems in the 4 weeks prior to survey. Of the survivors, 88.1 % reported having a PSA test since diagnosis of prostate cancer, with 93 % of them having it done at least once per year. Of the survivors, 82.6 % reported that a healthcare provider gave them information on prostate cancer. Of this 82.6 %, 86.4 % had this information provided by a urologist, 45.4 % by a primary care physician, and 29.2 % by an oncologist. The primary source of information for these survivors was "healthcare provider" (59.2 %). CONCLUSION: Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance versus active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment. Clinicians must assess post-treatment distress long after treatment has ended to identify when supportive care is needed. More informational resources should be allocated to prostate cancer survivors to ensure that they are well-educated about their prognosis. IMPLICATIONS FOR CANCER SURVIVORS: This study is needed to ensure that the post-treatment symptoms of prostate cancer survivors are properly addressed and managed by healthcare providers over the long term. PMID- 24214415 TI - Comparative dynamics and distribution of influenza drug resistance acquisition to protein m2 and neuraminidase inhibitors. AB - Although efficient influenza vaccines are designed on a regular basis, the only protection of human populations against an unforeseen virus such as during the H1N1 pandemic in 2009 might be antiviral drugs. Adamantanes and neuraminidase inhibitors (Oseltamivir) represent two classes of such drugs that target the viral matrix protein 2 and neuraminidase, respectively. Although the emergence of resistance to both drugs has been described, the timing and spread of the acquisition of either single or dual resistances by different hosts is still unclear. Using a multilayered phylogenetic approach based on relaxed molecular clocks and large-scale maximum likelihood approaches, we show that Adamantane resistance evolved multiple times in various subtypes and hosts, possibly in breeding contexts (swine); and Oseltamivir resistance was also found in different subtypes and hosts, but its transmission is only sustained in humans. Furthermore, the dynamics of the emergence of antiviral resistance were examined for each drug. This showed that although the first mutations conferring resistance to Adamantanes precede US Food and Drug Administration (FDA) approval, general resistance emerged 15-38 years post-drug approval. This is in contrast to Oseltamivir resistance mutations that emerged at most 7 years after FDA approval of the drug. This study demonstrates the power of large-scale analyses to uncover and monitor the emergence dynamics of drug resistance. PMID- 24214416 TI - Are researcher development interventions, alone or in any combination, effective in improving researcher behavior? A systematic review. AB - Academic institutions funded by the Clinical and Translational Science Awards (CTSA) Program of the National Institutes of Health were challenged recently by the Institute of Medicine to expand traditional mentoring of graduate and postdoctoral scholars to include training and continuing education for faculty, professional staff, and community partners. A systematic review was conducted to determine whether researcher development interventions, alone or in any combination, are effective in improving researcher behavior. PubMed, CINAHL, and Education Research Complete databases and select journals were searched for relevant articles published from January 2000 through October 2012. A total of 3,459 papers were identified, and 114 papers were retrieved for in-depth analysis. None included randomization. Twenty-two papers reported subjects with professional degrees, interventions, and outcomes. Interventions were meetings, outreach visits, colleague mediation, audit and feedback, and multifaceted interventions. Most studies reported multifaceted interventions (68.2%), often involving mentored learning experiences, and meetings. All studies reported a change in performance, including numbers of publications or grant applications. Nine studies reported changes in competence, including writing, presentation, or analytic skills, and performance in research practice (40.9%). Even as, the quality of evidence was weak to establish causal linkages between researcher development and improved researcher behavior, nearly all the projects (81.8%) received funding from governmental agencies, professional societies, or other organizations. Those who design researcher development activities and those who evaluate the programs are challenged to develop tools and conduct studies that measure the effectiveness, costs, and sustainability of researcher development in the CTSA Program. PMID- 24214411 TI - Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases. AB - Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire new traits to adapt to foreign milieu during the course of evolving into a new tumor in second organs. These comparisons also provided new information on understanding mechanism of vascular metastasis, organ-specific metastasis, and tumor dormancy. The collective results suggest a new hypothesis, biological resonance (bio-resonance) model. The hypothesis has two aspects. One is that primary cancer and matched metastasis have a common progenitor. The other is that both ancestors of primary cancer cells and metastatic cancer cells are under similar microenvironments and receive similar or same signals. When their interactions reach a status similar to primary cancer, metastasis will occur. Compared with previous hypotheses, the bio resonance hypothesis seems to be more applicable for cancer metastasis to explain how, when and where metastasis occurs. Thus, it has important implications for individual prediction, prevention and treatment of cancer metastasis. PMID- 24214417 TI - Establishing the Validity and Reliability of the Student Practice Evaluation Form Revised (SPEF-R) in Occupational Therapy Practice Education: A Rasch Analysis. AB - This study investigated construct validity and internal consistency of the Student Practice Evaluation Form-Revised Edition Package (SPEF-R) which evaluates students' performance on practice education placements. The SPEF-R has 38 items covering eight domains, and each item is rated on a 5-point rating scale. Data from 125 students' final placement evaluations in their final year study were analyzed using the Rasch measurement model. The SPEF-R exhibited satisfactory rating scale performance and unidimensionality across the eight domains, providing construct validity evidence. Only 2 items misfit Rasch model's expectations (both related to students' performance with client groups, which were often rated as not observed). Additionally, the internal consistency of each SPEF-R domain was found to be excellent (Cronbach's alpha = .86 to .91) and all individual items had reasonable to excellent item-total correlation coefficients. The study results indicate that the SPEF-R can be used with confidence to evaluate students' performance during placements, but continued validation and refinement are required. PMID- 24214418 TI - A new method for estimating the true score of subjects in the assessment based on the binary checklist. AB - Assessments of subjects by multiple raters are completed in several health research and practice arenas. As observed in interrater comparisons of checklists during assessment, raters generally make mistakes in assessment. Despite these errors, the average scores on all the checklists have been historically used to represent the subjects' true scores. The effect of the assessment rater error on these average scores has been seldom studied. In the present study, the effect of random rater error on subjects' average scores was investigated mathematically. The analysis based on a mathematical model revealed that average scores were truly representative only in special cases where raters made no assessment errors. In addition, average scores were poor estimates of the true score due to random assessment error. A new, more precise formula to estimate subjects' true scores was proposed. The method to apply this formula to actual checklist assessment data was demonstrated. PMID- 24214420 TI - An efficient palladium-catalyzed C-H alkoxylation of unactivated methylene and methyl groups with cyclic hypervalent iodine (i(3+) ) oxidants. AB - All the hype: The title reaction has been developed for the facile synthesis of a variety of complex alkyl ethers. Cyclic hypervalent iodine (I(3+) ) reagents serve as oxidants for this unique C?H alkoxylation reaction. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. Q=8-aminoquinoline-derived auxiliary. PMID- 24214421 TI - Small area estimation for semicontinuous skewed spatial data: an application to the grape wine production in Tuscany. AB - Linear-mixed models are frequently used to obtain model-based estimators in small area estimation (SAE) problems. Such models, however, are not suitable when the target variable exhibits a point mass at zero, a highly skewed distribution of the nonzero values and a strong spatial structure. In this paper, a SAE approach for dealing with such variables is suggested. We propose a two-part random effects SAE model that includes a correlation structure on the area random effects that appears in the two parts and incorporates a bivariate smooth function of the geographical coordinates of units. To account for the skewness of the distribution of the positive values of the response variable, a Gamma model is adopted. To fit the model, to get small area estimates and to evaluate their precision, a hierarchical Bayesian approach is used. The study is motivated by a real SAE problem. We focus on estimation of the per-farm average grape wine production in Tuscany, at subregional level, using the Farm Structure Survey data. Results from this real data application and those obtained by a model-based simulation experiment show a satisfactory performance of the suggested SAE approach. PMID- 24214422 TI - Disposition and metabolism of setipiprant, a selective oral CRTH2 antagonist, in humans. AB - BACKGROUND: Setipiprant, a tetrahydropyridoindole derivative, is a CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper [Th]-2 cells) antagonist that has the potential to be effective in the treatment of patients with diseases with an allergic etiology, such as allergic rhinitis and asthma. OBJECTIVES: This study investigated the disposition, metabolism, and elimination of setipiprant. STUDY DESIGN: In this open-label study, a single oral dose of 1,000 mg (14)C-labeled setipiprant was administered. PARTICIPANTS: Six healthy male subjects were enrolled in this study. RESULTS: The radioactive dose was almost completely recovered in feces (88.2 %) and to a smaller extent in urine (11.7 %). The main recovery route for unchanged setipiprant was feces (50 % of the radioactive dose). The recovered amount of unchanged setipiprant in urine accounted for 3.7 %. The two main metabolites were M7 and M9 with the intact tetrahydropyridoindole core of setipiprant. M7 and M9 are supposedly two distinct dihydroxy-dihydronaphthalene isomers assumed to be formed by intermediate epoxidation of the naphthyl ring followed by a hydrolytic epoxide ring-opening. M7 and M9 accounted for 20.0 and 15.3 % of the administered radioactive dose. Both metabolites were mainly excreted via feces and to a lesser extent via urine. M7 was the only metabolite quantifiable in plasma, but at concentrations consistently below 10 % of those of the parent drug. CONCLUSION: Setipiprant is mainly excreted in feces in the form of the parent drug and in smaller amounts as its metabolites M7 and M9. PMID- 24214423 TI - Relative collision cross sections of organic ions. AB - The relative collision cross sections sigma c of selected precursor ions that collide with helium at high ion kinetic energies (kiloelectronvolts) have been obtained by monitoring the ion beam attenuation at different collision pressures. A value for the total collision cross section is obtained, which includes contributions from different processes that lead to fragmentation, scattering, charge exchange, charge inversion, and stripping. For n-alkanes and n alkylbenzenes the sigma c value increases linearly by 0.1 per methylene group. Linear relationships exist between relative collision cross section and ionization cross section sigma i, and polarizability alpha of the corresponding neutral molecule, but different equations are required for the description of sigma c in each chemical series. A simple relationship, which requires only the chemical formula of the precursor ion, has been determined that can predict all relative collision cross sections with an average error of 3.5%. The total relative collision cross section increases with the size of the ion. The experimental results are in agreement with the predictions of the hard-sphere collision theory. The approach can be applied to determine the relative collision cross sections at different ion kinetic energy regimes and collisions with different target gases. PMID- 24214424 TI - High performance fourier transform ion cyclotron resonance mass spectrometry via a single trap electrode. AB - An open-ended cylindrical cell with a single annular trap electrode located at the center of the excitation and detection region is demonstrated for Fourier transform ion cyclotron resonance mass spectrometry. A trapping well is created by applying a static potential to the trap electrode of polarity opposite the charge of the ion to be trapped, after which conventional dipolar excitation and detection are performed. The annular trap electrode is axially narrow to allow the creation of a potential well without excessively shielding excitation and detection. Trapping is limited to the region of homogeneous excitation at the cell centerline without the use of capacitive coupling. Perfluorotributylamine excitation profiles demonstrate negligible axial ejection throughout the entire excitation voltage range even at an effective centerline potential of only -0.009 V. High mass resolving power in the single-trap electrode cell is demonstrated by achievement of mass resolving power of 1.45 * 10(6) for benzene during an experiment in which ions created in a high pressure source cubic cell are transferred to the low pressure analyzer single-trap electrode cell for detection. Such high performance is attributed to the negligible radius dependent radial electric field for ions cooled to the center of the potential well and accelerated to less than 60% of the cell radius. An important distinction of the single-trap electrode geometry from all previous open and closed cell arrangements is exhibition of combined gated and accumulated trapping. Because there is no potential barrier, all ions penetrate into the trapping region regardless of their translational energy as in gated trapping, but additional ions may accumulate over time, as in accumulated trapping. Ions of low translational kinetic energy are demonstrated to be preferentially trapped in the single-trap electrode cell. In a further demonstration of the minimal radial electric field of the single-trap electrode cell, positive voltages can be applied to the annular trap electrode as well as the source cell trap electrode to achieve highly efficient transfer of ions between cells. PMID- 24214425 TI - A comparison of the peptide fragmentation obtained from a reflector matrix assisted laser desorption-ionization time-of-flight and a tandem four sector mass spectrometer. AB - The types, extent, and overall distribution of peptide fragmentation produced by matrix-assisted laser desorption-ionization-postsource decay (MALDI-PSD) on a reflector time-of-flight mass spectrometer were compared with those obtained from high and low energy collision-induced dissociation (CID) on a four-sector mass spectrometer and from liquid secondary ion mass spectrometry (LSIMS) ion source fragmentation and LSIMS metastable ion (MI) decomposition on a two-sector mass spectrometer. The model peptides studied had sequences and compositions that yielded predominantly either N- or C-terminal fragmentation from CID. For des Arg(1) and des-Arg(9) bradykinin (i.e., H-PPGFSPFR-OH and H-RP-PGFSPF-OH, respectively), the types of fragment ions and the extent to which each type is formed in both MALDI-PSD and low energy CID spectra are remarkably similar. This observation suggests that both methods deposit comparable internal energies (IE) into [M + H](+) precursor ions. The distribution of N-terminal, C-terminal, immonium, and internal fragmentation from MALDI-PSD spectra of des-Arg(1) and des Arg(9) bradykinin did not change dramatically with respect to the terminal arginine position, contrary to those from LSIMS MI decomposition, high and low energy CID spectra. This observation in combination with the prominent immonium, internal, and minus 17 fragment ion types in PSD indicates that the imparted IE from MALDI and the 14 us of flight time may promote steady-state decomposition kinetics. Fragmentation distributions of MALDI-PSD spectra are also similar to those in LSIMS spectra. This implies that the distribution of protonation sites in [M + H](+) is comparable for both techniques. PMID- 24214426 TI - On the collision-activated fragmentation of proferrioxamines: Evidence for a succinimide-mediated mechanism. AB - The fragmentation mechanism of acyclic proferrioxamines has been studied by tandem mass spectrometry in a triple stage quadrupole mass analyzer by using activation in the collision cell as well as in the high pressure region prior to the first mass analyzer. The data suggest that proferrioxamines fragment preferentially at the hydroxamate bonds via cyclic rearrangement to succinimide derivatives. This pattern was observed most clearly for the peracetyl derivatives, in which the influence of terminal functional groups was masked. Free amino or carboxylic acid functions may modify this basic fragmentation pattern. Using hydrogen-deuterium exchange, we also were able to show that the hydrogen atoms that are "recruited" in the formation of ammonium ions are "acidic" ones from elsewhere in the molecule or the matrix. At the same time, this rules out that they originate from "activated" methylene groups, as previously proposed. PMID- 24214427 TI - Tandem mass spectrometry study of C-phenyl-N-tert-butyl nitrone spin adducts from in vitro rat liver microsomal metabolism of bromotrichloromethane and carbon tetrachloride. AB - Electron ionization and thermospray were used in conjunction with tandem mass spectrometry methods to identify trichloromethyl/C-phenyl-N-tert-butyl nitrone (PBN) spin adducts produced in rat liver microsomal dispersions that had been treated with reduced nicotinamide adenine dinucleotide phosphate (NADPH) generating system and BrCCl3 (or CCl4). In the identification of PBN spin adducts, a scan of precursors of m / z 57 was utilized to confirm the presence of PBN spin adducts, because PBN spin adducts produce m / z 57 from tert-butyl as a characteristic fragment. Use of deuterated PBN (PBN-d9 deuterated at tert-butyl; PBN-d 14 deuterated at both phenyl and tert-butyl) improved the recognition of PBN adducts in mixtures by precursor ion scans, because m / z 66 (which corresponds to the deuterated tert-butyl group) is characteristic and, unlike m / z 57, it is not a common fragment for any other compounds. Two new PBN spin adducts that were not detected before by electron paramagnetic resonance or mass spectrometry were identified by these methods for the first time. PMID- 24214428 TI - Analysis of serum protein precipitated with antiserum by matrix-assisted laser desorption ionization/time-of-flight and electrospray ionization mass spectrometry as a clinical laboratory test. AB - Serum transferrin precipitated with specific antisera was analyzed by matrix assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS) and electrospray ionization-mass spectrometry (ESI-MS). When analyzed by MALDI, transferrin showed signal peaks that clearly could be separated from ions of IgG present in the immunoprecipitate. By ESI-MS, when the immunoprecipitates were loaded through a microcapillary polymeric reversed-phase column connected to the electrospray ionization probe, the mass spectra of transferrin were observed with a high signal-to-noise ratio and good resolution. By MALDI/TOF-MS, the observed molecular weight of normal transferrin was ~ 1.2 ku smaller when analyzed in the reflectron mode than in the linear mode. The observed molecular weight of transferrin treated with sialidase was approximately the same in both modes. A comparison between the results obtained in both modes may help to estimate the number of sialic acids on the protein molecule. A transferrin isoform with a molecular weight of ~2.2 ku less than the normal species was identified in the serum of patients with a carbohydrate-deficient glycoprotein syndrome as well as in heavy alcohol consumers. PMID- 24214429 TI - Electrospray mass spectrometry of borane salts: The electrospray needle as an electrochemical cell. AB - Two borane salts ([(Me)4N][B3H8] and Cs[B3H8]) were examined by electrospray mass spectrometry in the positive ion mode. Acetonitrile solutions provided the most informative spectra; the salts exhibited a remarkable degree of clustering under electrospray conditions, and virtually all signals corresponded to cationic cluster ions of the general formula {[cation (m+)] x [anion (n-)] y }((mx - ny)+). In contrast, methanol solutions of these salts produced only B(OCH3) 4 (-) cluster ions under otherwise identical conditions. (11)B NMR analyses corroborate the identities of the methanol solution species that enter the electrospray source and the reaction product generated during the electrospray process. PMID- 24214430 TI - Electrospray ionization mass spectrometric study of encapsulation of amino acids by cyclodextrins. AB - Electrospray ionization (ESI) mass spectrometry has been used to study inclusion (host-guest) complexes of cyclodextrins (CDs) with amino acids. Host-guest complexes formed in solution are stable for characterization by ESI mass spectrometry: The relative abundances and the stoichiometry of the complexes formed in solution can, thus, be determined in the gas phase. The studies verified that beta- and gamma-cyclodextrin better accommodate protonated amino acids than alpha-cyclodextrin, and that chemically modified cyclodextrins such as heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) may show profound improvement in complexation. The preferential formation of DM-beta-CD-aromatic amino acid over DM-beta-CD-aliphatic amino acid complexes is confirmed by the experiments, and the relative gas-phase stabilities determined by repeller collimator collision-induced dissociation show an identical trend to the complexation in solution. Although molecular mechanics studies also may predict the encapsulation preference of protonated amino acids by cyclodextrins, only small differences in the total complexation energies are obtained because of the inability of the calculations to consider hydrophobic interactions. An experimental approach based on ESI mass spectrometry is, therefore, more reliable in predicting host-guest interactions that involve cyclodextrins and amino acids than the theoretical calculations that employ molecular mechanics models. PMID- 24214431 TI - Bond-selective photodissociation of aliphatic disulfides. AB - The photochemistry of aliphatic disulfides is presented. The photolysis products are photoionized with coherent vacuum ultraviolet radiation and analyzed by time of-flight mass spectrometry. With 248-nm excitation, the predominant dissociation pathway is S-S bond cleavage. With 193-nm excitation, S-S bond cleavage, C-S bond cleavage, and molecular rearrangements are all observed as primary processes. The branching ratio for S-S bond cleavage relative to C-S bond cleavage is typically 1-2 orders of magnitude greater at 248 run than 193 run. This wavelength dependence cannot be explained readily by photodissociation from the ground electronic state. The ground state S-S bond energy, ~ 280 kJ/mol, is much larger than the C-S bond energy, ~ 235 kJ/mol. If dissociation occurred from the ground state, higher wavelength radiation would be expected to favor the lower energy process, but the opposite effect is observed. Thus, excited state photochemistry is indicated. These results are discussed with respect to the differences between low and high energy collision-induced dissociation of peptides that contain disulfide linkages and to the possibility of achieving bond-selective photodissociation of such ions. PMID- 24214433 TI - Pediatric Exercise Science: back to the future. PMID- 24214434 TI - Oxygen uptake and endurance fitness in children, revisited. PMID- 24214435 TI - Large-scale youth physical fitness testing in the United States: a 25-year retrospective review. PMID- 24214436 TI - Changes in aerobic fitness in boys and girls over a period of 25 years: data from the Amsterdam Growth And Health Longitudinal Study revisited and extended. AB - In the Amsterdam Growth And Health Longitudinal Study (AGAHLS), a group of approximately 650 12- to 14-year-old boys and girls was followed in their growth, and development of their health their lifestyle including diet, physical activity and smoking. One of the main interests was the change in their aerobic fitness. From 12 to 36 years of age in total, eight repeated measurements were performed to measure peak oxygen uptake (peak VO2). In this study the data of peak VO2 are revisited and extended: We made use of all collected data as a mixed longitudinal design including cross-sectionally measured subjects as well as longitudinally measured subjects. This led to the availability of 1,194 boys and 1356 girls. With Generalized Estimating Equations (GEE) the longitudinal changes with chronological age and differences between boys and girls were analyzed. Teenage boys and girls increased their peak VO2 (ml/min) significantly (p < .001) until age 14 in girls and until age 17 in boys. However peak VO2 relative to bodyweight (peak VO2/BW) had significantly (p < .001) decreased over the whole age range from 12 to 36 in both sexes. Vigorous physical activity (VPA) also showed a decrease and was significantly (p < .001) related with lower peak VO2/BW (Beta = 0.001). This relation was stronger in boys than in girls. Because at the start of AGAHLS no fast responding metabolic instruments were available, future longitudinal studies about aerobic fitness should include also measurement of VO2 kinetics. PMID- 24214437 TI - Activity measurement: not simply child's play. PMID- 24214438 TI - Aerobic fitness and physical activity in children. AB - In Volume 1 of Pediatric Exercise Science (PES), a paper by Fenster et al. (25) investigated the relationship between peak oxygen uptake (peak VO2) and physical activity (PA) in 6- to 8-year-old children. They used both questionnaires and large-scale integrated activity monitors (LSIs) to estimate daily PA and determined peak VO2 using an incremental treadmill test to volitional exhaustion. They concluded that peak VO2 correlated well with PA as measured by LSIs but commented that questionnaire data were only weakly and nonsignificantly associated with LSI and peak VO2 data. Peak VO2 and PA are the most researched and reported variables in the 25-year history of PES. Yet, the assessment and interpretation of young people's aerobic fitness and PA remain problematic and any meaningful relationship between them during childhood and adolescence is shrouded with controversy. The present paper uses Fenster et al.'s (25) report as an indicator of where we were 25 years ago, outlines how far we have advanced since then, and suggests future directions of research in the study of aerobic fitness and PA. In the first volume of PES, Fenster, Freedson, Washburn, and Ellison (25) investigated the relationship between 6- to 8-year-old children's peak oxygen uptake (peak VO2) and physical activity (PA). Five boys and 13 girls participated in the study and their data were pooled for analysis. Peak VO2 was determined during an incremental treadmill test to voluntary exhaustion and PA was estimated using both questionnaires and large-scale integrated activity monitors (LSIs). On the basis of a significant interclass correlation coefficient of r = .59 between peak VO2 and the log of LSI average counts per hour Fenster et al. (25) concluded that "aerobic capacity, as measured by peak VO2 correlated well with physical activity as measured by LSI" (p.134). They also commented that questionnaire data were only weakly and nonsignificantly associated with LSI and peak VO2 data. Young people's peak VO2 and PA are the most researched and reported variables in the 25-year history of PES and yet the assessment and interpretation of peak VO2 and PA and any meaningful relationship between them during growth and maturation are still shrouded with controversy. The present paper uses Fenster et al.'s (25) work as an indicator of our understanding of young people's peak VO2 and PA in 1989, briefly reviews what we know in 2013, and suggests future directions of research. PMID- 24214439 TI - Back to the future: research trends in youth motivation and physical activity. PMID- 24214440 TI - Body composition in children. PMID- 24214441 TI - Youth resistance training: past practices, new perspectives, and future directions. AB - Since the publication of the seminal review on youth resistance training by Kraemer and colleagues in 1989, a compelling body of evidence has found that resistance training can be a safe, effective, and worthwhile method of conditioning for children and adolescents. New perspectives for promoting resistance exercise as part of a long-term approach to youth physical development highlight the importance of integrating resistance training into youth fitness programs. Youth who do not enhance their muscular strength and motor skill proficiency early in life may not develop the prerequisite skills and abilities that would allow them to participate in a variety of activities and sports with confidence and vigor later in life. The identification of asymptomatic children with muscular weaknesses or imbalances may facilitate the development of a management plan which should rectify movement limitations and educate children and their families about the importance of daily physical activity. PMID- 24214442 TI - The endocrine response to exercise and training in young athletes. AB - The manuscript "Plasma Somatomedin-C in 8- to 10-Year-Old Swimmers" by Denison and Ben-Ezra published in the first issue of Pediatric Exercise Science in 1989 was among the first to address the relationship between growth, the growth hormone (GH)/Insulin like growth factor-1 (IGF-1) axis, and exercise. Since their pioneering article, this topic has become of great interest to pediatricians and pediatric exercise researchers, and today our understanding of the effects of exercise training on the growth axis during childhood and puberty, on differences between systemic and local (i.e., muscle) responses to exercise, and our ability to use these responses to assist the adolescent competitive athlete in the evaluation of the training load have markedly improved. The aim of the present review is to summarize our current knowledge on this topic. PMID- 24214443 TI - Exercise and Cystic Fibrosis (CF) 2.0. AB - In 1989 we knew that exercise, including regular prescribed physical activity, could be safely performed and described some of the physiological responses to exercise in patients with cystic fibrosis (CF). Also in 1989, the genetic defect causing cystic fibrosis (CF) was identified leading to improvements in treatment that greatly extended the life span for these patients. Increased understanding of the factors limiting exercise capacity and of the important role of regular exercise in slowing the progression of CF and in modulating some of the effects of the genetic defect on airway function has led to the consensus that regular exercise should be part of the standard of care for this disease. PMID- 24214444 TI - Incorporation and metabolism of (14)C-labelled polyunsaturated fatty acids in juvenile gilthead sea bream Sparus aurata L. in vivo. AB - The incorporation, and the capacity for desaturation and elongation in vivo, of intraperitoneally-injected, (14)C-labelled n-3 and n-6 C18 and C20 PUFAs were investigated in juvenile gilthead sea bream, Sparus aurata. The results indicate that juvenile gilthead sea bream have only limited ability to convert CH PUFAs to C20 and C22 HUFAs in vivo. The data are consistent with the results from nutritional studies on larvae, postlarvae and fingerlings that have shown that gilthead sea bream require the provision of preformed eicosapentaenoic and docosahexaenoic acids in the diet. The impairment in the desaturase/elongase pathway was quantitatively and qualitatively similar to that found in turbot, Scophthalmus maximus, being at the level of the Delta5-desaturase. The low activity of Delta5-desaturase combined with the consistent finding that arachidonic acid is selectively retained in membrane phosphatidylinositol suggests that, in addition to eicosapentaenoic and docosahexaenoic acids, gilthead sea bream may also have a requirement for preformed arachidonic acid in the diet. PMID- 24214445 TI - Dietary carbohydrate utilization in cod (Gadus morhua): metabolic responses to feeding and fasting. AB - Moist diets with increasing amounts of carbohydrate (0.5%, 10% and 21% on a dry weight basis) were each fed to duplicate groups of cod (initial weight 370 g) for 8 weeks, after which all groups were fasted for 4 weeks. Protein energy was high and accounted for more than 70% of the gross energy content in all feeds, and the diets were maintained isocaloric by substituting lipid energy for carbohydrate energy. No indigestible binder was added. Excellent growth and feed conversion were obtained in all groups. After 4 weeks of fasting, fish previously fed diets with either 10% or 21% carbohydrate showed significantly higher weight loss than fish fed the diet without carbohydrate. Liver glycogen reached 10% of liver wet weight in fish fed diets containing 10% or 21% carbohydrate and 5% in fish receiving 0.5% carbohydrate after 8 weeks. Following 4 weeks of fasting, liver glycogen was reduced to similar levels in all fish. Plasma glucose levels 4 h after feeding were higher in fish fed the diets with 10% or 21% carbohydrate and plasma free amino acid levels (FAA) were lower, than in fish fed the diet containing 0.5% carbohydrate. Blood lactate concentrations were unaffected during the first 24 h after feeding. After 4 weeks of food deprivation, the levels were significantly reduced only in the 21% carbohydrate group. A link between glucagon and protein metabolism is suggested because plasma glucagon concentration followed the same pattern as the concentrations of plasma FAA throughout the study. Insulin and glucagon-like peptide (GLP) showed a covariation throughout the experiment. Reduced plasma insulin levels were seen after fasting concomitant with reduction in the levels of FAA and glucose. It is suggested that insulin secretion in cod is affected both by plasma FAA and glucose and that cod meets food deprivation by slowing down metabolism. PMID- 24214446 TI - Interaction of low density lipoproteins with liver cells in rainbow trout. AB - Liver is the main catabolic tissue for low density lipoprotein in rainbow trout (Gjoen and Berg 1992). We have investigated the interaction of LDL with isolated trout liver cells and liver membranes. (125)I-TC labelled trout LDL bound to isolated trout liver cells in a time dependent and saturable manner with an apparant Kd of 20.1 MUg/ml, suggesting the existence of a specific binding site on the surface of these cells. The binding was Ca(2+) dependent assessed by the 50% reduction obtained by 5 mM EDTA. Saturable binding to isolated trout liver membranes could also be demonstrated, but with lower affinity as compared to intact cells. Degradation of (125)I-TC-LDL in hepatocytes was also saturable as degradation could be inhibited about 60% by a 100 fold surplus of unlabelled LDL. The rate of degradation increased with temperature up to 20 degrees C. Both cell association (binding + uptake) and degradation were reduced down to 20% of control in the presence of microtubular and lysosomal inhibitors. Hepatic catabolism of trout LDL therefore seems to depend on receptormediated endocytosis, followed by lysosomal degradation. PMID- 24214447 TI - Hypoosmoregulation of larvae of the turbot, Scophthalamus maximus: drinking and gut function in relation to environmental salinity. AB - Measurement of blood osmolarity of pre-metamorphic turbot larvae demonstrated that hypoosmoregulation is well established in larvae 6 days post-hatch (121 degree-days) and older. Blood osmolarity of 121-420 degree-day larvae reared in 100% seawater was significantly greater than blood osmolarity of larvae reared in 50% seawater. Hypoosmoregulation involved drinking, but instantaneous drinking rates of 340 degree-day larvae reared in 100% seawater were only slightly more than those of similarly aged larvae reared in 50% seawater. Adaptation to environmental salinity involved changes in gut water absorption; 65-74% water absorption occurred in larvae reared in seawater compared to 30-35% water absorption in larvae reared in 50% seawater. Gastrointestinal water absorption occurred prior to the rectum. In seawater this occurred alongside a decrease in gut fluid osmolarity but desalting was apparently less significant than in adult fish. Absolute water absorption by the gut of 340 degree-day larvae reared in seawater was about 2-fold that of larvae held in 50% seawater, while the osmotic gradient between internal body fluids and environmental media differed by 4-fold, which implies changes the in water permeability of skin and/or developing gills. PMID- 24214448 TI - The role of cAMP in regulating the beta-adrenergic response of rainbow trout (Oncorhynchus mykiss) red blood cells. AB - The beta-adrenergic response of teleost red blood cells (RBCs) enables the fish to maintain or even enhance the oxygen affinity of haemoglobin during various stress situations. The role of CAMP in the pronounced beta-adrenergic response of hypoxic rainbow trout RBCs was studied. Rainbow trout RBCs were incubated with three different beta-agonists (noradrenaline, adrenaline and isoproterenol, 10( 9) - 10(-4) M) at two oxygen tensions (PO 2, 155 and 8 mmHg), and thereafter cAMP accumulation and cellular water content were measured.The cAMP concentration of non-stimulated trout RBCs was ca. 1200 nmol/kg dw. Of the three beta-agonists used, isoproterenol was the most effective in formation of cAMP, followed by noradrenaline and adrenaline. Oxygen tension affected the accumulation of cAMP in two ways. At physiological catecholamine levels (1-100 nM) there was either no difference between normoxic and hypoxic cells or a slight increase in the normoxic ones. At high catecholamine concentrations the accumulation of cAMP was greater in the hypoxic than in the normoxic cells. Oxygen tension also affected the magnitude of cell swelling but had no effect on the catecholamine concentrations causing half-maximal swelling (EC50-values). The results indicate that, at physiological catecholamine levels, the beta-adrenergic response of rainbow trout RBCs is mainly regulated on the level of the Na(+)/H(+) exchange. PMID- 24214449 TI - Stanniocalcin kinetics in freshwater and seawater european eel (Anguilla anguilla). AB - The kinetics and hypocalcemic potency of stanniocalcin (STC) were examined in freshwater and seawater eels. The secretion rate and the metabolic clearance rate of STC were calculated from the STC disappearance curve after intra-arterial injection of trout STC. Basal plasma STC concentrations in freshwater and seawater eels did not differ but the STC secretion rate and metabolic clearance rate in seawater eel were 70-75% higher than in FW eel. The increased STC distribution space in seawater eels suggests that the STC receptor density was increased. STC had a higher hypocalcemic potency in seawater than in freshwater eels. These observations support the hypothesis that seawater fish require more hormonal control over transcellular influx of calcium than freshwater fish. PMID- 24214450 TI - Seasonal changes in cortisol sensitivity and glucocorticoid receptor affinity and number in leukocytes of coho salmon. AB - To determine if there were organ-specific changes in immune responses or immune endocrine interaction, we monitored in vitro immune response, cortisol sensitivity and number and affinity of glucocorticoid receptors (GR) in leukocytes from freshwater-adapted juvenile coho salmon (Oncorhynchus kisutch) during the physiological changes that prepare them to enter the marine environment. During this period, absolute immune response declined, but splenic leukocytes generated more antibody-producing cells than did cells from anterior kidney. Splenic leukocytes were initially more sensitive to the suppressive effects of cortisol and had fewer GR than leukocytes from the anterior kidney. Leukocytes from the anterior kidney were initially insensitive to cortisol but developed sensitivity at about the same time as the dissociation constant and number of GR increased. In vitro incubation of anterior kidney leukocytes in cortisol altered GR variables when experiments were conducted during March through September but not during November through February. In some years, changes in GR or immune responses were correlated with plasma cortisol titers, but in other years there was no correlation. Thus, the exact relation between cortisol, GR and immune response in anadromous salmonids is unclear and other factors are involved. PMID- 24214451 TI - Effects of changes in plasma pH, CO2 and ammonia on ventilation in trout. AB - We investigated ventillatory responses to a plasma alkaloids and hypocapnia,a nd the basis for the ventilatory response to sodium bicarbonate (NaHCO3) infusion in rainbow trout. Plasma alkalosis and hypocapnia created by infusion of sodium hydroxide (NaOH) did not cause hypoventilation, whereas infusion of hydrochloric acid (HCl) caused vigorous hyperventilation, associated with an acidosis, a reduction in blood O2 content (CaO 2) and a release of circulating catecholamines. Infusion of NaHCO3 stimulated ventilation and caused an increase in plasma pH, total carbon dioxide content (CaCO 2) and catecholamine levels, and a reduction in oxygen tension (PaO 2). Infusion of ammonium bicarbonate (NH 4HCO3) caused hyperventilation and was associated with an increase in CaCO 2 and plasma total ammonia (Camm) and ammonia gas (NH3) concentration. Infusion of sodium chloride (NaClI) and Cortland's saline had no effect on ventilation. The results indicate that trout do not exhibit the ventilatory sensitivity to pH seen in terrestrial vertebrates. Ventilatory responses to NaHCO3 appear to have been a result of reductions in PaO 2, a release of catecholamines and an increase in CaCO 2 whereas responses to NH4HCO3 appear to have been a result of increases in CaCO 2 and Camm. PMID- 24214453 TI - Erratum. PMID- 24214452 TI - Referees of articles submitted to the journal in 1992. PMID- 24214454 TI - Contents, vol. 10, Nos. 1-6, April 1993. PMID- 24214456 TI - Giant breast tumors in a patient with Beckwith-Wiedemann syndrome. AB - Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with increased risk of embryonal tumors, such as Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma. We report on a patient with BWS that developed a giant fibroadenoma of the breast that was surgically removed. The tumor relapsed 8 months after the surgery and the patient underwent partial mastectomy. Although the patient presented several clinical features of BWS, a molecular diagnosis was not achieved despite extensive molecular investigations on both blood and tumor tissue. A SNP array revealed a de novo 7p22.1 loss in both blood and breast tumor involving the mismatch repair gene PMS2 gene that may be potentially associated with the breast tumor. In conclusion, it remains unclear whether BWS patients have an increased risk of breast lesions or a yet unknown molecular defect is responsible for the rare occurrence of this tumor in BWS. PMID- 24214457 TI - Competent care through the lens of the vascular patient: next steps in quality. PMID- 24214458 TI - Renewal and growth at JSFA in 2014. PMID- 24214459 TI - Innate humoral immune parameters in Tilapia zillii under acute stress by low temperature and crowding. AB - Redbelly tilapia (Tilapia zillii; Gervais, 1848) is one of the most valuable freshwater species in North Africa representing an important part of the continental production, especially in brackish lakes. In Algeria, T. zillii is distributed in several lakes and tributaries of some rivers in the south. Though some attempts are in progress to culture this species, many investigations covering its biology and farm management are still needed. In this sense, this is the first study attempting to evaluate some of the T. zillii immune parameters and valuable data to assess their health and well-being status. Thus, we have determined the levels of serum peroxidases as well as the alternative complement, antiprotease and bactericidal activities. Furthermore, we have also evaluated the potential impact of two acute stress factors, commonly found in fish farms, in these parameters. Although it was assessed that fish exposed to low temperatures or crowding were stressed, as indicated by their increased serum levels of cortisol and glucose, both acute stressors failed to significantly affect serum peroxidases as well as antiprotease and complement activities. However, the bactericidal activity was reduced in general but only in those exposed to crowding reached statistical significance. Further studies are needed to characterise the immune response in T. zillii as well as the effects that farming stresses may produce. PMID- 24214460 TI - Complications of mechanical chest compression devices. PMID- 24214461 TI - Recurrent repolarisation abnormalities in an athlete. PMID- 24214462 TI - Experiment and illusion in reproductive medicine. AB - The diffusion of medical technology is largely determined by the marketplace demands supported by national and historical contexts. Using the cases of cesarean delivery and newborn intensive care in the United States, this article presents the argument that the interaction of four factors accounts for the rapid diffusion of untested technologies. These factors are economic expansion in an unrestricted market, the vulnerability of the patient population, a social disposition towards emergency medicine, and the vested interest of medical specialists. PMID- 24214464 TI - Mother-infant bonding : A scientific fiction. AB - A study of the research on postpartum mother-infant bonding shows that results from poorly constructed research programs were published in major journals and became a part of hospital policy because the bonding concept was politically useful in the struggle between advocates of natural childbirth and managers of the medical model of birth. The concept was also uncritically accepted because it was consistent with a longstanding ideology of motherhood that sees women as the prime architects of their children's personalities. PMID- 24214465 TI - Predicting the future for newborns requiring intensive care. AB - When intensive care for newborns was introduced thirty years ago its primary goal was to improve the rates of survival of sick and premature infants. Medicine has been successful in attaining this goal; however, as more infants survive, the cost of intensive care and the additional cost of services and care for handicapped survivors continue to escalate. In order to curb the increasing cost of newborn intensive care, heightened initiatives directed at the prevention of premature births will be necessary. PMID- 24214463 TI - Methodological challenges in the study of fetal growth. AB - Several conceptual and methodological challenges must be solved in order to create knowledge that can be useful to pregnant women, their families, and any clinicians who serve them: (1) going beyond nominal and ordinal hypotheses and presenting estimates of conditional probabilities; (2) focusing on clearly defined outcomes; (3) modeling the relationship of fetal growth and length of gestation; (4) understanding the process of fetal growth even though most of our data is cross-sectional; (5) estimating the independent effects of genetics, race, ethnicity, maternal risk behaviors, medical prenatal care, and socioeconomic status on fetal growth and length of gestation; and (6) estimating the independent effects of maternal pre-pregnancy weight, weight gain during pregnancy, and nutrition on fetal growth and length of gestation. PMID- 24214466 TI - An exploration of the experience of Huntington's disease in family dyads: an interpretative phenomenological analysis. AB - Huntington's disease (HD) is a hereditary, late onset, neurodegenerative disorder. Children of affected parents have a 50 % chance of inheriting HD. Research into the psychological consequences of HD for the family has focussed on individual family members, but little is known about the ways in which its impact is jointly experienced by members of these families. This is particularly important due to the hereditary nature of HD. To address this, the current study examined the experiences of dyads within affected families. Seven parent/adult child dyads were interviewed jointly about their experiences and relationships with their family and each other and interpretative phenomenological analysis was used to analyse the resultant data. Identified themes were: "A spectre hanging over us": HD as a presence within the family, "Us against the world": Protection, knowledge and control, and "That could be me in 50 years": Cyclical changes in identity and role. These findings are examined in relation to previous research and indicate the need for an increased understanding of the needs of HD families. Clinical implications and suggestions for further research are discussed. PMID- 24214468 TI - 3D energetic metal-organic frameworks: synthesis and properties of high energy materials. PMID- 24214467 TI - High-resolution diffusion-weighted imaging for the separation of benign from malignant BI-RADS 4/5 lesions found on breast MRI at 3T. AB - PURPOSE: To determine whether readout-segmented echo-planar diffusion imaging (RESOLVE) improves separation of malignant versus benign lesions compared to standard single-shot echo-planar imaging (ss-EPI) on BI-RADS 4/5 lesions detected on breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Consecutive 3T breast MRI studies with BI-RADS 4/5 designation and subsequent biopsy or benign mastectomy were retrospectively identified. Freehand regions of interest (ROIs) were drawn on lesions and also on normal background fibroglandular tissue for comparison. Lesion-to-background contrast was evaluated by normalizing signal intensity of the lesion ROI by the normal background tissue ROI at b = 800. Statistical analysis used the Mann-Whitney/Wilcoxon rank-sum test for unpaired and Wilcoxon signed-rank for paired comparisons. RESULTS: Of 38 lesions in 32 patients, 10 were malignant. Lesion-to-background contrast was higher on RESOLVE than ss-EPI (1.80 +/- 0.71 vs. 1.62 +/- 0.63, P = 0.03). Mean apparent diffusion coefficient (ADC) was the same or lower on RESOLVE than ss-EPI, and this effect was largest in malignant lesions (RESOLVE 0.90 +/- 0.13; ss-EPI 1.00 +/- 0.13; median difference -0.10 (95% confidence interval [CI]: -0.17, -0.02) * 10(-3) mm(2) /sec; P = 0.014). By either diffusion method, there was a statistically significant difference between benign and malignant mean ADC (P < 0.001). CONCLUSION: Increased lesion-to-background contrast and improved separation of benign from malignant lesions by RESOLVE compared to standard diffusion suggests that RESOLVE may show promise as an adjunct to clinical breast MRI. PMID- 24214469 TI - Editorial. PMID- 24214470 TI - On the selection of signals. AB - In a previous paper, it was argued that alertness, selectivity (set), and processing capacity (consciousness) could be identified and studied as separate components of attention. The current paper develops this theme by showing that alertness does not affect the buildup of information within the memory system but only the rate at which a later system responds to that information. Thus, in standard reaction-time tasks, increased alertness produces a reduction in reaction 'time but no decrease in errors. In contrast, providing a model of the signal the S is to process improved both speed and accuracy. The,. presence of a model of what the S is to process varies the vertex neural response to that specific signal as compared to a mismatching signal in the first 200-300 msec after its presentation. Three accounts of this effect are: speeded processing of a matching stimulus, habituation of the electrical response to a matching stimulus, and prolonged or enhanced processing of a mismatch. Evidence favors the first of these explanations, but the other two cannot be dismissed as possible contributors to this effect. PMID- 24214471 TI - Some confounding factors in the study preparatory set in reaction time. AB - In Experiment I. the effects of the range of the distribution of preparatory intervals (Pls) on the effect of PI on RT was demonstrated, and disparate conclusions about the development of preparatory set were thereby accounted for to some degree. In Experiment II. both range of the PIs and their average value were examined in a factorial design for their effects on RT. and it was concluded that, for any average value, greater range will result in greater PI effects; and for any range, greater average values will result in smaller PI effects on RT. PMID- 24214472 TI - Critical issues in interference theory. AB - Critical issues in the theoretical and experimental analysis of interference processes in retention are reviewed. The evolution of classical two-factor theory is traced, and the strengths and weaknesses of the contemporary version of this p6sition are examined. Recent critiques of Current interference theories by Martin (1971a) and Greeno, James, and Da Polito (1971) are reviewed and examind. New conceptualizations of interference proposed by these authors, which place major emphasis on retrieval dependencies and on the role of encoding and retrieval processes, are considered and evaluated. PMID- 24214473 TI - Race vs belief as determinants of attraction, in a group interaction context. AB - Three experiments which tested the' effects of race vs belief similarity as determinants of prejudiced responding in a live interaction situation,are reported. Two black and two white confederates engaged a white S in a discussion of an issue (ROTC in Experiments I and II and abortion in III). One white and one black confederate agreed with the S's position and the other pair disagreed. Ss then rated all four confederates on a variety of scales. Results showed strong belief effects in all three experiments but very few race effects. A few measures showed a "renegade effect" against dissimilar white confederates. It was concluded that simply increasing the power and realism of the experimental situation does not in any important way increase the number of racially prejudiced responses. Some conditions which may elicit strong and consistent race prejudice effects are discussed. PMID- 24214474 TI - Stimulus-naming effects at different stages of motor paired-associate learning. AB - In a combined verbal and motor paired-associate task, nonsense names and button pushing responses were learned for three random shapes, with verbal training beginning after 3, 12, or 24 motor learning trials. Earlier studies indicated that concurrent verbal and motor learning produce a strong tendency for the naming and button-pushing responses to be learned in "consistent" pairs. According to the theoretical analysis presented, the verbal-motor consistency is explained by the development of name-button associations. It was predicted that these associations affect both motor errors and correct responses, that their effects are greater for correct responses, and that attenuation of the effects due to delay in verbal training is gr, eater for motor errors. The results are in good agreement with the predictions, and they suggest that name-button associations develop rapidly even under delayed verbal training. PMID- 24214475 TI - Effects of serial position and set size in auditory recognition memory. AB - Auditorially presented lists of from one to six digits were memorized by Ss with instructions to scan the memory set to determine the presen'ce or absence of a single auditorially presented probe digit. Results showed cooccurrence of parallel linear increases in decision time with list length for positive and negative responses and effects of serial position of probes in the memory lists. A comparison with two previous studies using visual presentation of materials suggests faster encoding of auditorially presented probes but similarity in processing time in memory once probes have been encoded. PMID- 24214476 TI - Perceived frequency of concrete and abstract words. AB - Studies are reported which show that concrete and abstract words of equal objective frequency (based on available , word counts) are not perceived as being equal. The abstract word has greater perceived frequency than the concrete word. The judged variety of contexts in which a word appears correlates very highly with perceived frequency. The results have relevance to the design of learning studies in which concrete and abstract words are used. and also to the interpretation of such experiments. PMID- 24214477 TI - Degree of training and the novelty transfer effect. AB - Four groups of 40 Ss were given transfer tests following 2.4, 6, or 8 14-trial blocks of paired-associate training with unequal stimulus frequencies and then retested after a further training period in which the same compound stimuli were presented at equal frequencies. The novelty effect, in which Ss respond to new combinations of training components by giving the response associated with the least frequent component, was obtained in every transfer test. It was concluded that the novelty effect is a mode of responding that is produced by differential frequencies during early learning and which, once adopted, is retained by Ss regardless of whether the frequency differential is maintained. PMID- 24214478 TI - The role of configuration and target discriminability in a visual search task. AB - Ss sorted through decks of cards bearing five-element patterns, separating those in which all five were identical from those in which one of the five was different from the remaining four. Sorting time depended on the configuration and size of the pattern in which the elements were arranged but was independent of the goodness of these patterns. It was concluded that Ss did not attend to the patterns themselves, but just to the elements comprising them in searching for the discrepant element. The differences owing to the patterns appear to be due in part to the compactness of the configurations. PMID- 24214479 TI - Transformations on sets in short-term memory: Temporal and spatial factors influencing deletion. AB - An individual's ability to perform a deletion operation on sets in short-term memory was explored in a reaction time (RT) experiment. Special attention was given to the importance, for deletion, of temporal and spatial variables. Ss did perform a deletion operation. The speed of correct recognition was influenced by both the delay between the deletion (D) set and a test item and the serial order correspondence between identical items in the to-be-remembered or positive (P) set and the D set. PMID- 24214480 TI - Set size and order requirements in immediate memory. AB - Three types of order requirements in the immediate recall of number sequences were investigated in two experiments. Experiment I examined written recall and Experiment II spoken recall. Natural serial recall was found to be superior to same order and free recall (a) in Experiment I because repeated correct intrusions were reduced, and (b) in Experiment II because more responses were produced. Implications for the analysis of mnemonic devices were briefly introduced. PMID- 24214481 TI - Isolation of massed- and distributed-practice items. AB - In four experiments, massed-practice (MP) or distributed-practice (DP) items were isolated from other items in a list presented either visually or auditorially for free recall. For three independent groups, the first, second, or both presentations of an item were isolated. Locus of isolation had a marginal influence on recall. When MP items were isolated, they were recalled better than DP items. Isolating the DP items enhanced the MP-DP effect. The results are congruent with the idea that the MP-DP effect in free recall results, in part, from differential rehearsal. PMID- 24214482 TI - Perceptual encoding in comparative judgments of race. AB - Ss made comparative judgments along the black-white racial dimension using opposite response sets ("Which is blacker?" or "Which is whiter?"). Three classes of pictures were used: B (black),W (white), and M (racially mixed). I or the BM judgments. "Which is whiter?" took significantly longer. The MW and BW judgments showed no difference between response instructions. Analysis of the stimuli showed that skin tone was not the primary perceptual attribute used in racial encoding. The observation of a funnel effect in the judgment latencies is shown to be consistent with other research demonstrating the effect of response set in comparative judgments Further. the results support sociological observations about the cultural use of the linguistic labels "black" and "white" PMID- 24214483 TI - Processing demands of sequential information. AB - Three experiments examined the processing capacity required to use sequential information in a serial reaction time task with partially predictable sequences. The first two experiments varied the response stimulus interval (RSI) between 0 and 500 msec and found the relative advantage of the high-probability stimulus to be independent of the length of the RSI. The third experiment compared utilization of sequential information either with or without a secondary task. The secondary task did not affect the high-probability stimulus but did increase the amount of time required to respond to the low-probability events. The results are discussed in terms of the attentional demands of memory access. PMID- 24214484 TI - On the nature of central processing in choice reactions. AB - A procedure for generating values of central processing uncertainty was developed from positive response data in a varied-set version of the Sternberg choice reaction task. This is a logical extension of a previously validated procedure for data from a fixed-set version of the same task. Both procedures provide information on the additive components of reaction time. It was concluded that S resolves more uncertainty in the varied-set than in the fixed-set situation. It was concluded also that S performs a rechecking operation prior to emitting a negative response, and this rechecking apparently involves less information than does the original testing for stimulus classification. This, in turn, suggests that rechecking is a self-terminating process with regard to display information. The results also imply that stimulus classification is partially serial and partially parallel, so a hybrid model may be appropriate for this task. PMID- 24214485 TI - Accuracy of three novel predictive methods for measurements of fat mass in healthy older subjects. AB - This study evaluated the agreement of novel anthropometric equations and established indirect methods (skinfold thickness and bioimpedance analysis) with reference methods [dual X-ray absorptiometry (DXA) and air displacement plethysmography (ADP)] for fat mass assessment (FM) in older subjects. METHODS: Forty subjects (M/F = 15/25, age = 61-84 years, BMI = 18-37 kg/m(2)) were recruited. The agreement of the following predictive equations was evaluated: body adiposity index (BAI), BAI-Fels and Clinica Universidad de Navarra-body adiposity estimator (CUN-BAE). RESULTS: BAI estimates were comparable to DXA (Delta +/- 2SD = 0.4 +/- 6.0 kg, p > 0.05) but not to ADP (Delta +/- 2SD = -2.8 +/- 7.2 kg, p < 0.001); BAI-Fels estimates were comparable to DXA (Delta +/- 2SD = 0.8 +/- 5.5 kg, p > 0.05) but not to ADP (Delta +/- 2SD = -4.0 +/- 6.9 kg, p < 0.001). The difference between CUN-BAE and ADP was not significant (Delta +/- 2SD = -0.4 +/- 5.6 kg, p > 0.05), whereas it significantly overestimated DXA (Delta +/- 2SD = 2.8 +/- 5.4 kg, p < 0.001). ADP significantly overestimated FM compared to DXA (Delta +/- 2SD = 3.2 +/- 5.4 kg, p < 0.001) and the measurement bias was significantly correlated with BMI in men (p = 0.004). CONCLUSIONS: The accuracy of the three anthropometric indexes is dependent on the choice of the reference method. The variability of the FM estimates was large and these indexes cannot be recommended for the assessment of FM in older subjects. PMID- 24214486 TI - Linking physiology to toxicity using DILIsym(r), a mechanistic mathematical model of drug-induced liver injury. AB - The drug development industry faces multiple challenges in the realization of safe effective drugs. Computational modeling approaches can be used to support these efforts. One approach, mechanistic modeling, is new to the realm of drug safety. It holds the promise of not only predicting toxicity for novel compounds, but also illuminating the mechanistic underpinnings of toxicity. To increase the scientific community's familiarity with mechanistic modeling in drug safety, this article seeks to provide perspective on the type of data used, how they are used and where they are lacking. Examples are derived from the development of DILIsym((r)) software, a mechanistic model of drug-induced liver injury (DILI). DILIsym((r)) simulates the mechanistic interactions and events from compound administration through the progression of liver injury and regeneration. Modeling mitochondrial toxicity illustrates the type and use of in vitro data to represent biological interactions, as well as insights on key differences between in vitro and in vivo conditions. Modeling bile acid toxicity illustrates a case in which the over-arching mechanism is well accepted, but many mechanistic details are lacking. Modeling was used to identify measurements predicted to strongly impact toxicity. Finally, modeling innate immune responses illustrates the importance of time-series data, particularly in the presence of positive and negative feedback loops, as well as the need for data from different animal species for better translation. These concepts are germane to most mechanistic models, although the details will vary. The use of mechanistic models is expected to improve the rational design of new drugs. PMID- 24214487 TI - Serial progression of cortical and medullary thymic epithelial microenvironments. AB - Thymic epithelial cells (TECs) provide key instructive signals for T-cell differentiation. Thymic cortical (cTECs) and medullary (mTECs) epithelial cells constitute two functionally distinct microenvironments for T-cell development, which derive from a common bipotent TEC progenitor. While seminal studies have partially elucidated events downstream of bipotent TECs in relation to the emergence of mTECs and their progenitors, the control and timing of the emergence of the cTEC lineage, particularly in relation to that of mTEC progenitors, has remained elusive. In this review, we describe distinct models that explain cTEC/mTEC lineage divergence from common bipotent progenitors. In particular, we summarize recent studies in mice providing evidence that mTECs, including the auto-immune regulator(+) subset, derive from progenitors initially endowed with phenotypic properties typically associated with the cTEC lineage. These observations support a novel "serial progression" model of TEC development, in which progenitors serially acquire cTEC lineage markers, prior to their commitment to the mTEC differentiation pathway. Gaining a better understanding of the phenotypic properties of early stages in TEC progenitor development should help in determining the mechanisms regulating cTEC/mTEC lineage development, and in strategies aimed at thymus reconstitution involving TEC therapy. PMID- 24214488 TI - Plasmid-mediated transformation tropism of chlamydial biovars. AB - Chlamydia trachomatis and C. muridarum are human and mouse pathogens, respectively, which show high conservation of gene order and content. Both species contain a common 7.5-kb plasmid that is an important virulence factor. Recently described transformation systems have been used to characterize C. trachomatis L2 plasmid gene functions; however, similar studies have not been reported for C. trachomatis ocular tropic serovar A or the mouse strain, C. muridarum. Here, we have conducted genetic experiments with C. trachomatis serovar A and C. muridarum and report the following: (1) successful transformation of C. muridarum and C. trachomatis serovar A is restricted to a shuttle vector with a C. muridarum or C. trachomatis serovar A plasmid backbone, respectively; (2) transformation of plasmid-deficient C. muridarum with the C. muridarum-based shuttle vector complement glycogen accumulation and inclusion morphology; and (3) C. muridarum plasmid-encoded Pgp4 is a regulator of chromosomal (glgA) and plasmid (pgp3) virulence genes. In summary, our findings show a previously unrecognized and unexpected role for the chlamydial plasmid in its transformation tropism and confirm the plasmids regulatory role of virulence genes in C. muridarum. PMID- 24214489 TI - Family history and clefting as major criteria for CHARGE syndrome. AB - CHARGE syndrome is an autosomal dominant malformation syndrome associated with mutations in CHD7. The condition is typically sporadic with few familial cases reported. The diagnosis of CHARGE syndrome is based on a combination of major and minor criteria comprised of structural and functional abnormalities, most of which are part of the original CHARGE acronym, although additional anomalies have been added. To date, family history has not been considered in the diagnostic criteria. Here we report a family with a previously unreported missense mutation in exon 31 of CHD7, in which family history played a role in the diagnosis of CHARGE syndrome. Given the tremendous phenotypic variability and the dominant nature of CHARGE syndrome, we propose that family history be included as a major diagnostic criterion. A positive family history would include any individual with an apparently isolated unilateral major CHARGE anomaly or someone with a few of the minor features. Our cases support this proposal; had family history not been considered in this case, CHD7 testing might not have been pursued, leading to incomplete medical follow-up and erroneous genetic counseling. Additionally, with the increased incidence of orofacial clefting in this family, as well as in the literature, we suggest that cleft lip and/or palate be added to the major diagnostic criteria for CHARGE syndrome. PMID- 24214490 TI - Salt effects on hydrophobic-core formation in folding of a helical miniprotein studied by molecular dynamics simulations. AB - We have investigated effects of salt ions on folding events of a helical miniprotein chicken villin headpiece subdomain HP36. Low concentrations of ions alter electrostatic interactions between charged groups of a protein and can change the populations of conformers. Here, we compare two data sets of folding simulations of HP36 in explicit water solvent with or without ions. For efficient sampling of the conformational space of HP36, the multicanonical replica-exchange molecular dynamics method was employed. Our analyses suggest that salt alters salt-bridging nature of the protein at later stages of folding at room temperature. Especially, more nonnative, nonlocal salt bridges are formed at near native conformations in pure water. Our analyses also show that such salt-bridge formation hinders the fully native hydrophobic-core packing at the final stages of folding. PMID- 24214491 TI - Sex dependent pharmacokinetics and bioequivalence--time for a change. AB - Bioequivalence studies have historically been performed largely in young males and then extrapolated to be applicable to both sexes at any age. This tendency continues today, yet a number of studies have shown that drug pharmacokinetics can be significantly different in women than in men, even as regards intra patient variability. Some of our assumptions when treating women may not be accurate if we base our decisions on information obtained from studies conducted in men. Furthermore, women can have various physiological states that can affect drug disposition, and one of the most significant is pregnancy. PMID- 24214492 TI - Orthostatic hypotension is associated with lower cognitive performance in adults aged 50 plus with supine hypertension. AB - OBJECTIVES: This study investigated the association between orthostatic hypotension (OH), supine hypertension (SH), and cognitive performance. METHODS: Four thousand six hundred and ninety participants of The Irish Longitudinal Study on Ageing (TILDA) were studied. SH was defined as systolic blood pressure (SBP) greater than or equal to 140 mmHg and/or diastolic blood pressure (DBP) greater than or equal to 90 mmHg, measured following supine rest (10 minutes). OH was defined as a sustained drop of greater than or equal to 20 mmHg SBP or greater than or equal to 10 mmHg DBP at 20, 30, 60, and 90 seconds following orthostasis. Cognitive performance tests assessed global function, executive function, processing speed, memory, and attention from which z-scores were computed. Multivariate adjusted analysis was performed comparing cognitive scores by OH status overall and in SH and non-SH groups separately. RESULTS: Thirty-nine percent had baseline SH (n = 1,868) and demonstrated a greater orthostatic fall in SBP (p < .0001) and DBP (p < .0001). This group had a higher prevalence of OH at all time-points, and scored lower in tests across all cognitive domains. No overall association between OH and cognitive performance was seen. However, SH subjects with OH scored significantly worse (adjusted) than SH subjects without OH, in domains of global cognition (30 seconds poststand beta = -0.15; 99% confidence interval -0.29, -0.14; p = .004) and executive function (20 seconds poststand; beta = -0.11; 99% confidence interval -0.22, -0.01; p = .006). There was also an indication toward lower cognition in all nonsignificant analyses. OH was not associated with cognitive performance in non-SH subjects. CONCLUSION: In conclusion, individuals with SH (defined as BP > 140/90 mmHg) coupled with OH measured using phasic BP had lower global and executive cognitive performance than those with SH but without OH. PMID- 24214493 TI - The risk/safety assessment of transgenic crops: the transportability of data. AB - This paper presents the activities and publications of Organisation for Economic Co-operation and Developments (OECD's) Working Group on Harmonisation of Regulatory Oversight in Biotechnology and the Task Force for the Safety of Novel Foods and Feeds. The main outputs of the work are the Series of "consensus documents" of the respective groups. These documents compile information which is intended to be used by those involved in the business of risk/safety assessment. These documents are one means of ensuring the transportability of data amongst authorities. An increasing trend in both the Working Group and Task Force is to consider crop species which are relevant to tropical regions and therefore to countries that are not necessarily members of the OECD. For example, the Working Group has recently published a consensus document on bananas and plantains while the Task Force has published a document on cassava. This trend towards crops of greater interest in the tropics is likely to continue into the future. PMID- 24214494 TI - Inducible, tightly regulated and non-leaky neuronal gene expression in mice. AB - The Tetracycline (Tet)-controlled inducible system is the most widely used reversible system for transgene expression in mice with over 500 lines created to date. Although this system has been optimized over the years, it still has limitations such as residual transgene expression when turned off, referred to as leakiness. Here, we present a series of new Tet-OFF transgenic mice based on the second generation tetracycline-responsive transactivator system. The tTA-Advanced (tTA2(S)) is expressed under control of the neuron-specific Thy1.2 promoter (Thy OFF), to regulate expression in the mouse brain. In addition, we generated a lacZ reporter line, utilizing the P tight Tet-responsive promoter (P(tight)-lacZ), to test our system. Two Thy-OFF transgenic lines displaying two distinct patterns of expression were selected. Oral doxycycline treatment of Thy-OFF/P tight-lacZ mice demonstrated tight transgene regulation with no leak expression. These new Thy OFF mice are valuable for studies in a broad range of neurodegenerative diseases such as Alzheimer's disease and related forms of dementia, where control of transgene expression is critical to understanding mechanisms underlying the disease. Furthermore, P tight-lacZ reporter mice may be widely applicable. PMID- 24214495 TI - Assessing unintended effects of a mammary-specific transgene at the whole animal level in host and non-target animals. AB - Risk assessment in transgenic plants is intrinsically different than that for transgenic animals; however both require the verification of proper transgene function and in conjunction, an estimate of any unintended effects caused by expression of the transgene. This work was designed to gather data regarding methodologies to detect pleiotropic effects at the whole animal level using a line of transgenic goats that produce the antimicrobial protein human lysozyme (hLZ) in their milk with the goal of using the milk to treat childhood diarrhea. Metabolomics was used to determine the serum metabolite profile of both the host (lactating does) and non-target organism (kid goats raised on control or hLZ milk) prior to weaning (60 days), at weaning (90 days) and 1 month post-weaning (120 days). In addition, intestinal histology of the kid goats was also carried out. Histological analysis of intestinal segments of the pre-weaning group revealed significantly wider duodenal villi (p = 0.014) and significantly longer villi (p = 0.028) and deeper crypts (p = 0.030) in the ileum of kid goats consuming hLZ milk. Serum metabolomics was capable of detecting differences over time but revealed no significant differences in metabolites between control and hLZ fed kids after correction for false discovery rate. Serum metabolomics of control or hLZ lactating does showed only one significant difference in an unknown metabolite (q = 0.0422). The results as a whole indicate that consumption of hLZ milk results in positive or insignificant intestinal morphology and metabolic changes. This work contributes to the establishment of the safety and durability of the hLZ mammary-specific transgene. PMID- 24214496 TI - Employment following chemoradiotherapy in glioblastoma: a prospective case series. AB - PURPOSE: Radiotherapy (RT) and temozolomide (TMZ) for glioblastoma (GBM) has resulted in longer survival. Uncertainties exist regarding quality of survival. This study aims to determine the rate of patients returning to previous employment (EM) following treatment. METHODS: Eligible patients were diagnosed with GBM, aged 18-70 years, and treated with intensity-modulated radiotherapy to 60 Gray and TMZ (EORTC Protocol) between July 2007 and July 2011. EM was defined as paid work. Exclusion criteria included patients without histological confirmation of WHO grade IV glioblastoma, those not in paid employment in the 2 month period prior to diagnosis, or mothers of pre-school aged children not working. Data were collected on EM prior (EM pre) and after RT at 6 and 12 months (EM 6 m, EM 12 m). Rate of EM was analysed in regards to baseline performance status (ECOG), neurological deficits (MRC scale) and median survival. RESULTS: One hundred twelve patients were identified with median follow-up of 15.5 months and median survival 18 months (95%CI, 15-21 months). Seventy-one patients were working prior to diagnosis and eligible for analysis. Twenty patients returned to work (28 %) by EM 6 months and 19 patients (27 %) by EM 12 months. EM 6 months was strongly associated with ECOG and MRC status, with only 1 of 37 patients (3 %) with neurological deficit returning to work compared with 21 of 36 (58 %) intact patients. Of good performance status patients not returning to work, factors included presence of income insurance, family financial support or treatment-related symptoms. CONCLUSION: A modest proportion of patients with GBM return back to work at 6 and 12 months following radiotherapy with the majority demonstrating the lowest level of neurological deficit prior to RT. IMPLICATIONS FOR CANCER SURVIVORS: Return to work following treatment does occur but it is not a common outcome. PMID- 24214497 TI - Supporting cancer survivors' participation in peer review: perspectives from NCI's CARRA program. AB - PURPOSE: Including cancer survivors in the peer review of cancer-related research is increasingly valued as a strategy for bringing the "patient perspective" to discussions of research merit and human subject protection. Because integrating lay stakeholders into peer review poses challenges, this qualitative study explored the perspectives of experienced patient advocates to identify programmatic supports for survivors' participation. METHODS: Semi-structured telephone interviews were conducted with a purposive sample of 19 cancer survivors and 6 administrators involved in the National Cancer Institute's Consumer Advocates in Research and Related Activities program. Audio-recorded interviews were transcribed verbatim and analyzed via thematic content analysis. Participants were highly educated and included survivors of breast, prostate, and blood-related cancers. RESULTS: Interviewees emphasized the importance of adequately preparing survivors to serve as advocates. Given the intellectual challenge of peer review, interviewees noted the need for intensive and ongoing training on how to review proposals, and they identified mock reviews and peer mentoring as effective strategies to complement didactic instruction. Participants also stressed the need to address social challenges inherent in advocate-scientist encounters. In addition to training for both advocates and scientists, participants reported that opportunities for informal social interaction were important for facilitating collaboration. Finally, participants recommended structuring advocates' role so as to give them a voice via equal voting privileges and protected opportunities to speak. CONCLUSIONS: Programs that seek to include cancer survivors in peer review can prepare advocates for the intellectual and social challenges of working with scientists through careful attention to training, networking, and programmatic design. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors have been leaders in developing a role for patient advocates in the peer review of research. As the concept of patient centered outcomes continues to gain currency, lessons learned from early programs for patient inclusion in peer review can help to inform future efforts aimed at giving patients a voice in shaping agendas for health-related research. PMID- 24214498 TI - Breast cancer experience and survivorship among Asian Americans: a systematic review. AB - INTRODUCTION: Breast cancer is the most common cancer in Asian American women, and the number of Asian American breast cancer survivors is rapidly increasing. Although Asian Americans are one of the fastest growing and most heterogeneous ethnic groups in the United States, limited data exist in regard to their breast cancer experience and survivorship. METHODS: A systematic review of the breast cancer experience literature was conducted and included studies of Asian Americans or their subgroups as a major category of study participants. Of the 125 studies reviewed, 10 qualitative studies, 10 quantitative studies, 5 studies that used a mixed-method approach, and 1 intervention study met the criteria for inclusion. RESULTS: Qualitatively, Asian Americans reported unmet physical and emotional needs and challenges during survivorship. Quantitative studies consistently found that socioeconomic status, cultural health beliefs, immigration stress, acculturation level, English proficiency, social support, and spirituality associated with Asian American breast cancer patients' health behaviors and health-related quality of life (HRQOL). Studies also revealed significant variation in breast cancer reaction and HRQOL within Asian American subgroups. CONCLUSIONS: Although research on Asian American breast cancer experience and survivorship is sparse, we concluded that Asian Americans experience disrupted HRQOL following breast cancer diagnosis and treatment, interwoven with their cultural and socio-ecological system, and that programs focused on improving cancer survivorship outcomes among this ethnic minority group are limited. Most studies have concentrated on the West coast population, and there is significant underrepresentation of longitudinal and intervention studies. Implications for study design, measurement, and future research areas are also included. IMPLICATIONS FOR CANCER SURVIVORS: The results highlight a need to understand ethnic differences and to take into account social, cultural, and linguistic factors in breast cancer survivorship experiences among Asian American subgroups as a means to develop culturally relevant and linguistically appropriate interventions designed to improve HRQOL. PMID- 24214499 TI - FATE-HD: a spatially and temporally explicit integrated model for predicting vegetation structure and diversity at regional scale. AB - During the last decade, despite strenuous efforts to develop new models and compare different approaches, few conclusions have been drawn on their ability to provide robust biodiversity projections in an environmental change context. The recurring suggestions are that models should explicitly (i) include spatiotemporal dynamics; (ii) consider multiple species in interactions and (iii) account for the processes shaping biodiversity distribution. This article presents a biodiversity model (FATE-HD) that meets this challenge at regional scale by combining phenomenological and process-based approaches and using well defined plant functional groups. FATE-HD has been tested and validated in a French National Park, demonstrating its ability to simulate vegetation dynamics, structure and diversity in response to disturbances and climate change. The analysis demonstrated the importance of considering biotic interactions, spatio temporal dynamics and disturbances in addition to abiotic drivers to simulate vegetation dynamics. The distribution of pioneer trees was particularly improved, as were all undergrowth functional groups. PMID- 24214500 TI - The effects of familiarity and practice on naming pictures of objects. AB - Ss were given a paired-associate learning task, using nonsense shapes as stimuli and object names which varied in Thorndike-Lorge frequency as responses. Between each block of learning trials, Ss named the nonsense shapes and a set of line drawings of objects. While naming latencies for the shapes were unaffected by name frequency, there was an effect of frequency on naming a control set of pictures of objects. The frequency effect for the pictures decreased significantly with practice. When the Ss were asked to name pictures of the objects having the names previously learned for the nonsense shapes, an effect of frequency appeared, the size of the effect being the same as that found for the control pictures after practice. The frequency effect disappeared when the shapes were reintroduced. PMID- 24214501 TI - The Stroop phenomenon and its use in the stlldy of perceptual, cognitive, and response processes. AB - The present review summarizes empirical findings and theoretical views related to the Stroop color-word test. Lyperimental findings were emphasized in contrast to the results of correlational studies, and the bulk of the material was produced since the 1966 review of Jensen and Rohwer. One purpose of the review was to illustrate use of the Stroop paradigm as a too! for the stud)' of other psychological processes. The incompleteness, and in some cases the mappropnateness, of existing explanatisons of the Stroop phenomenon also were discussed. nt]mis|The author is grateful to E. C. Dalrymple-Alford. George S. Harker, and Anne Treisman for their comments on an earlier draft of the paper. PMID- 24214502 TI - Must overlearned lists be scanned? AB - Ss were presented given names as test items and asked either to indicate whether each test name was a member of a previously memorized list of names or whether each test name was the name of one of their siblings. The data indicated that the memorized hst of names was scanned in a serial fashion but that (disregarding the case where S had just one sibling) S did not have to scan the list of his own siblings' names to decide about a test name. PMID- 24214503 TI - Competing responses and the processing of irrelevant information. AB - A number of studies have shown that performance of identification and discrimination tasks is detrimentally affected by irrelevant information, yet other studies have failed to find such decrements. It is suggested that these contradictory findings depend on whether S must make difficult discriminations among the relevant stimuli, the irrelevant stimuli, or between the relevant and irrelevant stimuli. The role of irrelevant information in these tasks is to enhance or amplify the competihg responses engendered by the difficult discriminations. Irrelevant information enhances competing responses by increasing the information processing requirements of a task. The results of various studies of irrelevant information seem to be in good agreement with the assertions. PMID- 24214504 TI - Storage and retrieval of low-frequency words*. AB - Retneval of words as a function of their language frequency was studied by having Ss attempt to recogruze the words, recall the words after one presentation, or produce (think of) the words from their initial bigrams. It was found that one reason many low-frequency words could not be thought of (often necessary in anagram and other problem-solving tasks) was because they were not stored by S. as measured by failure to recognize them as words. Those low-frequency words that were stored were more difficult to retrieve than high-frequency words, both in production and in recall. High-frequency words did not exhibit failure of storage. but showed considerable difficulty in retrieval. both in recall and in production. PMID- 24214505 TI - Context effects and the recall of comparative sentences. AB - Clark and Card (1969) have proposed that semantic components underlie memory for comparative (C) sentences. To test this hypothesis, six groups of 15 Ss each were given different sets of C sentences. In line with the theory, Ss tended to remember unmarked adjectives better than marked ones and positive constructions better than negatives. However, contrary to the theory, they also tended to bias their responding either toward the negative or the equative form. A two-stage theory of recall, based on the memory schema-memory trace distinction, is proposed to account for these data. PMID- 24214506 TI - Role of response imagery on stimulus recognition*. AB - This experiment investigated the role of response imagery on recognition of stimulus terms following associative training. Ss learned to associate 12 high imagery or low-imagery responses with trigram stimuli by the study-associative matching procedure. Half the pairs were consistently paired and half were re paired anew on each trial. Following associative training, Ss were given a stimulus recognition and an associative matching task The results indicated that the probability of stimulus recognition, given correct associative matching, was greater when the responses were high-imagery rather than low-imagery. In contrast, no rehable response imagery effects were found for the probability of stimulus recognition, given incorrect associative matching. It was argued that the locus of the response imagery effect was primarily during retrieval rather than during encoding. PMID- 24214507 TI - Ready-signal effects as a function of experimental design in simple reaction time. AB - In the between-S design, 20 Ss had a visual ready signal presented on each trial; for another 20 Ss, the ready signal was always absent. The within-S design consisted of 40 Ss that experienced both ready-signal conditions in semirandom order. Two intensities of a 1,000-Hz tone were used as the response signals Ready signal manipulation had pronounced effects under the within-S but not the between S design irrespective of response-signal intensity. PMID- 24214508 TI - A sequential analysis of the partial reinforcement extinction effect in children*. AB - In a series of studies employing children between the ages of 7.6 and 10.6 years of age guessing on a modified Humphreys's board, extinction training was administered following either continuous reinforcement or various schedules of partial reinforcement training. Besides the observation of a partial reinforcement extinction effect, it was found that resistance to extinction appeared to be regulated by those sequential variables specified by extensions of Capaldi's theory of instrumental learning. PMID- 24214509 TI - On the independence of judged frequencies for items presented in successive lists*. AB - In an experiment examining retroactive interference effects in a frequency judging task, all Ss were presented with a list of words occurring varying numbers of times according to either a massed- or distributed-practive (MP or DP) schedule. They were then asked to judge how often each word had occurred. Following this, Ss were given one of four types of second tasks a second list with different items followed by a frequency-judging task for that list (Condition New): a second list with items repeated from the first list but with different frequencies for each item, while either maintaining items as either MP or DP items (Condition Same) or switching MP items to DP, and vice versa (Condition Reverse): followed by a frequency-judging task for the second-list frequencies only: or a puzzle task for the amount of time required for second list presentation and judgment in the other conditions (Condition None). Finally, all Ss were asked to recall List 1 frequencies, List 2 frequencies were less discriminable in Conditions Same and Reverse than in Condition New. Recall of List 1 frequencies, however, was not different for these three groups, but was poorer than in List 2 frequency judgments were not independent of List 1 frequencies. PMID- 24214510 TI - Perceptual vs conceptual categorization. AB - The study considered whether Ss use the same strategies in categorizing biographical descriptions as in perceptual classifications. A biographical description consisted of a person's age, income, number of children, and years of education. The Ss were asked to classify these descriptions as residents of two different suburbs in order to compare the results with a previous study using schematic faces. The 123 Ss were assigned to one of three alternative organizations of the descriptions: a table, a "name" organized paragraph in which each person was successively described, or an "attribute" organized paragraph in which each attribute was successively described. Essentially the same results were obtained for schematic faces and biographical descriptions, except for a few differences which were attributed to the use of more realistic categories (suburbs) in the present study. When more realistic categories are used, a S's prior experience can influence which attributes he emphasizes and possibly his formation of an abstract prototype. PMID- 24214511 TI - The effects of auditory shadowing on recognition of information received visually. AB - When Ss attend to one auditory message, they have no permanent memory for a second auditory message received simultaneously. Generally, it has been argued that a similar effect would occur crossmodally. This hypothesis was tested in the present experiment for messages presented to visual and auditory modalities. All Ss were tested for recognition of information presented either while shadowing or while hearing but not shadowing a passage of prose presented to one ear. One group heard a list of concrete nouns in their other ear. Three other groups received (1) printed words. (2) pictures of objects easily labeled, or (3) pictures of objects difficult to label. The shadowing task produced a decrement m recognition scores for the first three groups but not for the group receiving pictures of objects difficult to label. Further, the shadowing task interfered more with information received auditorily than with any form of visual information. These results suggest that information received visually is stored in a long-term modality-specific memory that may operate independently of the auditory modality. PMID- 24214512 TI - Linear representation of temporal location and Stevens's law. AB - Ss were asked to indicate points 1 week, 7 months, 3 years, and 9 years in the past and future on two time lines representing birth to present and present to death. Data for 90 college-age Ss fit a psychophysical power function following Stevens's law. with negatively accelerated growth indicating proportionately greater linear representation of periods nearer to the present. Variability was greater for the representations of the future than of the past, with monotonic increases in variability as distance from the present increased. PMID- 24214513 TI - Part-list recall following part-whole learning. AB - Following five trials of part-list free recall learning and six trials of whole list free recall learning, Ss were asked to recall the part-list items on two successive trials. Experimental Ss whose whole list contained all of the part list items recalled more part-list items than did control Ss whose whole list contained none of the part-list items. The data are inconsistent with current notion of subjective organization. PMID- 24214514 TI - The Ranschburg effect: Stimulus variables and scoring criterion*. AB - The influence of stimulus variables on recall of intraserially repeated items was investigated with a parametric manipulation of the rate of presentation (.4, .8, or 1.6 sec/item), modality of presentation (auditory or visual), and sequence length (7 or 10 items long). The results indicated that the Ranschburg effect, poorer recall of repeated items than of corresponding control items, is relatively insensitive to stimulus manipulations. The Ranschburg effect was found to be localized primarily at the position of the second occurrence of the repeated item. The influence of the repeated items did not generalize to the other (nonrepeated) items of the sequence. Differences in the Ranschburg effect as a function of the scoring criterion were discussed. The results were interpreted as being consistent with a guessing bias interpretation of the Ranschburg effect. PMID- 24214515 TI - Repetition and laterality effects on recognition memory for words and pictures*. AB - Recognition memory for a list of words was tested by presenting a series of items with Ss instructed to make positive responses to targets (list items) and negative responses to distractors (nonlist items). The test items were either words or pictures, and they were presented tachistoscopically either to the left or right visual field. The results showed mean response latencies to be generally faster for stimuli presented to the right visual field. Response times were faster for target and distractor stimuli on their second test presentations than on initial tests, but this effect was much larger for targets. Repetitions were shown to decrease the amount of time necessary to execute the stimulus encoding and initial retrieval stages of recognition. This was also true, although to a lesser extent, if different stimulus forms (words or pictures) were used on the two tests. Subsequent recognition stages, including memory search and decision processes. were apparently independent of test stimulus form. PMID- 24214516 TI - Attention decrement, temporal variation, and the primacy effect in impression formation. AB - Three experiments which tested the attention decrement explanation of the primacy effect in impression formation are reported. A memory-crowding interpretation of attention decrement would predict a decrease in primacy as the interval between traits is increased. Mild support was obtained in Experiment I but not in II or III. Overall. the magnitude of the primacy effect was independent of intertrait temporal variation. Decrement in attention is the most attractive theoretical explanation for the commonly obtained primacy effect. However, the results of the present series of studies suggest that this explanation is not tenable and that other theoretical mechanisms will be required to account for primacy effects. PMID- 24214517 TI - Influence of marihuana on storage and retrieval processe in memory. AB - Following presentation and immediate free recall testing of 10 20-word lists, 48 Ss were divided into two groups, one of which received an oral dose of marihuana extract calibrated to 20 mg of Delta(1)-THC and one of which received placebo. One hour later, all Ss were administered delayed recall, recognition, and order tests on the first set of words. Presentation of another set of 10 lists followed, and there were immediate recall and delayed recall, recognition, and order tests on these words. Performance of drug and placebo Ss did not differ significantly for any of the first delayed tests. However, the performance of drug Ss was poorer than that of placebo Ss on immediate recall, delayed recall, and delayed recognition of the second set of lists. We concluded that retrieval of information relevant to the occurrence or nonocurrence of an event was not affected by marihuana intoxication. Storage difficulties probably account for memory deficits due to the drug, and these difficulties appear to occur in the process of transferring information from short-term to long-term memory. PMID- 24214518 TI - The accuracy of a disposable noninvasive core thermometer. AB - PURPOSE: Perioperative hypothermia is still a common occurrence, and it can be difficult to measure a patient's core temperature accurately, especially during regional anesthesia, with placement of a laryngeal mask airway device, or postoperatively. We evaluated a new disposable double-sensor thermometer and compared the resulting temperatures with those of a distal esophageal thermometer and a bladder thermometer in patients undergoing general and regional anesthesia, respectively. Furthermore, we compared the accuracy of the thermometer between regional and general anesthesia, since forehead microcirculation might differ between the two types of anesthesia. METHODS: We assessed core temperature in 36 general anesthesia patients and 20 patients having regional anesthesia for orthopedic surgery. The temperatures obtained using the double-sensor thermometer were compared with those obtained with the distal esophageal thermometer in the general anesthesia population and those obtained with the bladder thermometer in regional anesthesia patients. RESULTS: In our general anesthesia patients, 90% (95% confidence interval [CI] 85 to 95) of all double-sensor values were within 0.5 degrees C of esophageal temperatures. The average difference (bias) between the esophageal and double-sensor temperatures was -0.01 degrees C. In patients undergoing regional anesthesia 89% (95% CI 80 to 97) of all double-sensor values were within 0.5 degrees C of bladder temperatures. The average difference (bias) between the bladder and double-sensor temperatures was -0.13 degrees C, limits of agreement were -0.65 to 0.40 degrees C. CONCLUSIONS: In a perioperative patient population undergoing general or regional anesthesia, the accuracy of the noninvasive disposable double-sensor thermometer is comparable with that of the distal esophageal and bladder thermometers in routine clinical practice. Furthermore, the sensor performed comparably in patients undergoing regional and general anesthesia. PMID- 24214519 TI - Bioinspired total synthesis of montanine-type Amaryllidaceae alkaloids. PMID- 24214521 TI - Clinical practice guideline: CYP2D6 genotyping for safe and efficacious codeine therapy. AB - This guideline is intended to provide a basis for informed decision-making regarding genetic testing to identify those individuals who will not benefit from codeine therapy, as well as those who are at an increased risk for codeine induced toxicity. This guideline addresses the following key questions: 1) Should genetic testing for CYP2D6 be performed in patients prior to the initiation of codeine therapy? 2) How should patients with an indication for codeine therapy be managed based on their genotyping results for CYP2D6? PMID- 24214522 TI - Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series. AB - BACKGROUND: A tibial-pedal access method is needed for patients with advanced peripheral artery disease (PAD) unable to tolerate common femoral artery (CFA) access and intervention due to body habitus or comorbidities. This is the first case series reporting an alternative technique to revascularize such patients. Using ultrasound (US) and the tibio-pedal arterial minimally invasive retrograde revascularization (TAMI) technique, operators accessed, and revascularized the lower extremity completely via tibial-pedal arterial access. METHODS: This retrospective, single-center, case series recorded on 23 patients who underwent TAMI revascularization during a seven-month period in 2012, demonstrating the feasibility and safety of the TAMI technique. Eighty-three percent had Rutherford Classification IV-VI. Ultrasound guidance aided all tibial access. Demographics, vascular symptoms, disease characteristics, success, procedure length, time to discharge, immediate and 30-day complications were collected. Comparison was sought with 201 unmatched patients treated via traditional CFA access over a similar period. RESULTS: Arterial access was successful in all patients. Thirty six lesions were treated. Lesion success (ability to cross lesion and achieve post treatment stenosis <30%) was achieved in 95% of patients. 25% of lesions were above the knee. Average prestenosis was 92.5%; average poststenosis 12%. No major complications were noted. Two patients presented within 30 days with access site pain. Access site peroneal artery pseudo-aneurysms were diagnosed and treated percutaneously with covered stents. Both recovered with no sequelae. CONCLUSION: Retrograde tibio-pedal intervention appears to be safe and effective. The TAMI technique offers an alternate revascularization method for critically ill advanced PAD patients. PMID- 24214523 TI - HIV-Mycobacterium tuberculosis co-infection: a 'danger-couple model' of disease pathogenesis. AB - Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection. PMID- 24214524 TI - Plasma paraoxonase 1 arylesterase activity in D-galactose-induced aged rat model: correlation with LDL oxidation and redox status. AB - OBJECTIVE: There is much evidence linking the involvement of oxidative stress in the pathogenesis of aging. Paraoxonase 1 (PON1) is an HDL-associated antioxidant enzyme that inhibits the oxidative modification of low-density lipoproteins (LDL). We have investigated the changes in plasma PON1 activity, LDL oxidation, radical scavenging activity and lipid peroxidation in D-galactose-induced aging rat model and also compared the results with 24-month naturally aged rats. METHOD: Arylesterase activity of PON1, susceptibility of LDL for oxidation, plasma radical scavenging activity and plasma thiobarbituric acid reactive substances (TBARS) were measured in normal control rats (4-months-old control rats subjected to D-galactose-induced experimental aging, and 24-month-old naturally aged rats). RESULTS: There was a significant decrease in plasma PON1 arylesterase activity in both subcutaneous D-galactose-treated groups and 24 month-old aged rats (P < 0.05, for each). TBARS, an oxidative stress marker, was seen to increase in the experimental groups (P < 0.01). In both subcutaneous galactose-treated and naturally aged rats, there was a significant rise in plasma LDL oxidation (P < 0.05, for each). However, radical scavenging activity was decreased significantly (P < 0.01) in both groups, as compared to control. CONCLUSIONS: The D-galactose-induced rat model of aging mimics the naturally aged rat with reference to PON1 arylesterase activity and susceptibility to LDL oxidation. The results emphasize the importance of PON1 with respect to aging and its association with redox balance of the body. PMID- 24214525 TI - Prevalence and risk factors associated with goat gastrointestinal helminthiasis in the Sertao region of Paraiba State, Brazil. AB - Gastrointestinal helminthiasis represents an obstacle to goat raising, causing severe damage to herds such as growth retardation, weight loss, and even death. In this study, we aimed to determine the prevalence and risk factors associated to goat gastrointestinal helminthiasis in the Sertao region of Paraiba State, Brazil. A total of 256 goats from 54 farms were systematically sampled. Blood and fecal samples were collected from each animal for egg per gram (EPG), larval culture, and packed cell volume (PCV) analyses. We found that 79.3% of the goats investigated were parasitized with gastrointestinal helminths. Significant correlation (p = 0.004) was observed between the EPG and PCV of the animals studied, and it was observed that the EPG increases as the PCV decreases. In the larval culture, the most prevalent helminth was Haemonchus sp. (83.2%). Age and sex were significant variables (p <= 0.20) for the development of gastrointestinal helminths: 86.8% of animals over 36 months of age and 81.7% of females were infected. The variable type of animal exploitation was also significant, with 90.3% (p <= 0.20) of the animals presenting double suitability (milk and meat). The Sertao region of Paraiba State presents high prevalence of gastrointestinal helminthiasis in goats, and age and type of animal exploitation are the most relevant risk factors to the development of these parasites. PMID- 24214527 TI - Trisomy 13 (Patau syndrome) and congenital heart defects. PMID- 24214526 TI - Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration. AB - PURPOSE: To compare quantification of the amide proton transfer (APT) effect pre- and post-gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect. MATERIALS AND METHODS: Four patients with internal carotid stenosis were recruited. APT imaging was acquired pre- and post-contrast in two sessions (before and after surgery) to assess the extent of relaxation time, T1 , change on APT effect calculated using magnetization transfer ratio asymmetry analysis at offsets of +/-3.5 ppm relative to water resonance. Statistical and modeling evaluations were performed on the pre- and post-contrast APT effect to study the sensitivity to contrast administration. RESULTS: Before surgery, the post-contrast T1 was estimated to drop <10% of the pre-value for the majority of the patients. After surgery, higher post-contrast T1 reductions were observed in all the patients (maximum decrease was about 20% of the pre-value). Consistent differences between pre- and post-contrast were seen in the APT effect quantified using the asymmetry measure in most regions of the brain, with significant differences found in the white matter at the group level and in 25% of the individual patient results. CONCLUSION: APT imaging should be performed prior to Gd administration to avoid potential misinterpretation of the APT effect. PMID- 24214528 TI - Stigma and psychiatric morbidity among mothers of children with epilepsy in Zambia. AB - BACKGROUND: Epilepsy-associated stigma contributes substantially to the social, medical, and economic burden of disease for people with epilepsy (PWE), but little is known about its impact on caregivers of PWE. METHODS: To better understand stigma experienced by caregivers of PWE, factors that influence caregiver stigma, and the effect of stigma on a caregiver's psychologic well being, we interviewed 100 caregivers of children with epilepsy in Zambia. Questions assessed maternal knowledge, attitudes, and practices related to epilepsy, maternal stigma, mother's proxy report of child stigma, and maternal psychiatric morbidity. RESULTS: Of 100 mothers, 39 (39%) indicated that their child was stigmatized because of his or her epilepsy. Maternal proxy report of child stigma was highly correlated with maternal stigma (OR: 5.4, p=0.04), seizure frequency (p=0.03) and seizure severity (p=0.01). One in five of 100 mothers (20%) reported feeling stigmatized because of their child's epilepsy. Higher maternal stigma was associated with lower familial and community support (ORs: 65.2 and 34.7, respectively; both p<0.0001) as well as higher psychiatric morbidity (OR: 1.2; p=0.002). Formal education and epilepsy knowledge were associated with decreased maternal stigma (ORs: 0.8 and 0.7, respectively; both p<0.001). CONCLUSIONS: One in five mothers of PWE feel stigmatized because of their child's epilepsy. As maternal stigma is associated with psychiatric morbidity, educating caregivers about epilepsy and screening for anxiety and depression are warranted. PMID- 24214529 TI - Opportunities to improve domestic hygiene practices through new enabling products: a study of handwashing practices and equipment in rural Cambodia. AB - BACKGROUND: Lack of a dedicated place and equipment for handwashing has been associated with poor practice of handwashing with soap in the home in developing communities where the practice is needed to reduce diarrhea diseases and respiratory infections. METHODS: We conducted formative research on handwashing knowledge, attitudes, practices and equipment and investigated the need and demand for dedicated handwashing equipment to enable improved hygiene practices and enhance handwashing performance for health in rural Cambodian homes where water is collected and stored. Responses to closed and open-ended questions and structured observation of a demonstration of handwashing by the mother or another female adult child caretaker in 79 households were used to identify handwashing occasions, evaluate handwashing equipment and competency, investigate attitudes and structural barriers to handwashing with soap, and assess use of and interest in dedicated handwashing equipment. RESULTS: We found significant evidence of the need for handwashing enabling equipment to eliminate unsafe domestic water handling during handwashing and reduce structural barriers to routine handwashing with soap in Cambodian homes dependent on stored water supplies. Substantial interest in dedicated handwashing equipment and in specific equipment features was measured. CONCLUSIONS: Findings suggest household demand for and uptake of affordable household handwashing facilities incorporating desired features and functionality could be generated in Cambodia to support improved domestic hygiene practices. PMID- 24214530 TI - Mucosal delivery of antigen-coated nanoparticles to lungs confers protective immunity against tuberculosis infection in mice. AB - Mucosal boosting of BCG-immunised individuals with a subunit tuberculosis (TB) vaccine would be highly desirable, considering that the lungs are the principal port of entry for Mycobacterium tuberculosis (MTB) and the site of the primary infection and reactivation. However, the main roadblock for subunit TB vaccine development is the lack of suitable adjuvants that could induce robust local and systemic immune responses. Here, we describe a novel vaccine delivery system that was designed to mimic, in part, the MTB pathogen itself. The surface of yellow carnauba wax nanoparticles was coated with the highly immunogenic Ag85B Ag of MTB and they were directed to the alveolar epithelial surfaces by the incorporation of the heparin-binding hemagglutinin adhesion (HBHA) protein. Our results showed that the i.n. immunisation of BCG-primed BALB/c mice with nanoparticles adsorbed with Ag85B-HBHA (Nano-AH vaccine) induced robust humoral and cellular immune responses and IFN-gamma production, and multifunctional CD4+ T cells expressing IFN-gamma, IL-2 and TNF-alpha. Mice challenged with H37Rv MTB had a significantly reduced bacterial load in their lungs when compared with controls immunised with BCG alone. We therefore conclude that this immunisation approach is an effective means of boosting the BCG-induced anti-TB immunity. PMID- 24214531 TI - Flowering phenology and its implications for management of big-leaf mahogany Swietenia macrophylla in Brazilian Amazonia. AB - PREMISE OF THE STUDY: Flowering phenology is a crucial determinant of reproductive success and offspring genetic diversity in plants. We measure the flowering phenology of big-leaf mahogany (Swietenia macrophylla, Meliaceae), a widely distributed neotropical tree, and explore how disturbance from logging impacts its reproductive biology. METHODS: We use a crown scoring system to estimate the timing and duration of population-level flowering at three forest sites in the Brazilian Amazon over a five-year period. We combine this information with data on population structure and spatial distribution to consider the implications of logging for population flowering patterns and reproductive success. KEY RESULTS: Mahogany trees as small as 14 cm diam flowered, but only trees > 30 cm diam flowered annually or supra-annually. Mean observed flowering periods by focal trees ranged from 18-34 d, and trees flowered sequentially during 3-4 mo beginning in the dry season. Focal trees demonstrated significant interannual correlation in flowering order. Estimated population level flowering schedules resembled that of the focal trees, with temporal isolation between early and late flowering trees. At the principal study site, conventional logging practices eliminated 87% of mahogany trees > 30 cm diam and an estimated 94% of annual pre-logging floral effort. CONCLUSIONS: Consistent interannual patterns of sequential flowering among trees create incompletely isolated subpopulations, constraining pollen flow. After harvests, surviving subcommercial trees will have fewer, more distant, and smaller potential partners, with probable consequences for post-logging regeneration. These results have important implications for the sustainability of harvesting systems for tropical timber species. PMID- 24214532 TI - Susceptibility of human and avian influenza viruses to human and chicken saliva. AB - Oral cavity can be an entry site of influenza virus and saliva is known to contain innate soluble anti-influenza factors. Influenza strains were shown to vary in their susceptibility to those antiviral factors. Whether the susceptibility to the saliva antiviral factors plays any role in the host species specificity of influenza viruses is not known. In this study, the antiviral activity of human and chicken saliva against human and the H5N1 avian influenza viruses were investigated by hemagglutination inhibition (HI) and neutralization (NT) assays. In comparison to human influenza viruses, H5N1 isolates showed reduced susceptibility to human saliva as measured by HI and NT assays. Interestingly, an H5N1 isolate that bind to both alpha2,3- and alpha2,6-linked sialic acid showed much higher HI titers with human saliva, suggesting that the susceptibility profile was linked to the receptor-binding preference and the presence of alpha2,6-linked sialic in human saliva. On the other hand, the H5N1 isolates showed increased HI titers but reduced NT titers to chicken saliva as compared to human influenza isolates. The human salivary antiviral components were characterized by testing the sensitivity to heat, receptor destroying enzyme (RDE), CaCl2/EDTA dependence, and inhibition by mannan, and shown to be alpha- and gamma-inhibitors. These data suggest that the H5N1 HPAI influenza virus had distinctive susceptibility patterns to human and chicken saliva, which may play some roles in its infectivity and transmissibility in these hosts. PMID- 24214533 TI - RBF1, a plant homolog of the bacterial ribosome-binding factor RbfA, acts in processing of the chloroplast 16S ribosomal RNA. AB - Plastids (chloroplasts) possess 70S ribosomes that are very similar in structure and function to the ribosomes of their bacterial ancestors. While most components of the bacterial ribosome (ribosomal RNAs [rRNAs] and ribosomal proteins) are well conserved in the plastid ribosome, little is known about the factors mediating the biogenesis of plastid ribosomes. Here, we have investigated a putative homolog of the bacterial RbfA (for ribosome-binding factor A) protein that was identified as a cold-shock protein and an auxiliary factor acting in the 5' maturation of the 16S rRNA. The unicellular green alga Chlamydomonas reinhardtii and the vascular plant Arabidopsis (Arabidopsis thaliana) both encode a single RbfA-like protein in their nuclear genomes. By generating specific antibodies against this protein, we show that the plant RbfA-like protein functions exclusively in the plastid, where it is associated with thylakoid membranes. Analysis of mutants for the corresponding gene (termed RBF1) reveals that the gene function is essential for photoautotrophic growth. Weak mutant alleles display reduced levels of plastid ribosomes, a specific depletion in 30S ribosomal subunits, and reduced activity of plastid protein biosynthesis. Our data suggest that, while the function in ribosome maturation and 16S rRNA 5' end processing is conserved, the RBF1 protein has assumed an additional role in 3' end processing. Together with the apparent absence of a homologous protein from plant mitochondria, our findings illustrate that the assembly process of the 70S ribosome is not strictly conserved and has undergone some modifications during organelle evolution. PMID- 24214534 TI - Deletion mutagenesis identifies a haploinsufficient role for gamma-zein in opaque2 endosperm modification. AB - Quality Protein Maize (QPM) is a hard kernel variant of the high-lysine mutant opaque2. Using gamma-irradiation, we created opaque QPM variants to identify opaque2 modifier genes and to investigate deletion mutagenesis combined with Illumina sequencing as a maize (Zea mays) functional genomics tool. A K0326Y QPM deletion mutant was null for the 27- and 50-kD gamma-zeins and abolished vitreous endosperm formation. Illumina exon and RNA sequencing revealed a 1.2-megabase pair deletion encompassing the 27- and 50-kD gamma-zein genes on chromosome 7 and a deletion of at least 232 kb on chromosome 9. Protein body number was reduced by over 90%, while protein body size is similar to the wild type. Kernels hemizygous for the gamma-zein deletion had intermediate 27- and 50-kD gamma-zein levels and were semivitreous, indicating haploinsufficiency of these gene products in opaque2 endosperm modification. The gamma-zein deletion further increased lysine in QPM in its homozygous and hemizygous states. This work identifies 27-kD gamma zein as an opaque2 modifier gene within the largest QPM quantitative trait locus and may suggest the 50-kD gamma-zein also contributes to this quantitative trait locus. It further demonstrates that genome-wide deletions in nonreference maize lines can be identified through a combination of assembly of Illumina reads against the B73 genome and integration of RNA sequencing data. PMID- 24214536 TI - Population genomic analysis reveals no evidence for GC-biased gene conversion in Drosophila melanogaster. AB - Gene conversion is the nonreciprocal exchange of genetic material between homologous chromosomes. Multiple lines of evidence from a variety of taxa strongly suggest that gene conversion events are biased toward GC-bearing alleles. However, in Drosophila, the data have largely been indirect and unclear, with some studies supporting the predictions of a GC-biased gene conversion model and other data showing contradictory findings. Here, we test whether gene conversion events are GC-biased in Drosophila melanogaster using whole-genome polymorphism and divergence data. Our results provide no support for GC-biased gene conversion and thus suggest that this process is unlikely to significantly contribute to patterns of polymorphism and divergence in this system. PMID- 24214535 TI - Leaf oil body functions as a subcellular factory for the production of a phytoalexin in Arabidopsis. AB - Oil bodies are intracellular structures present in the seed and leaf cells of many land plants. Seed oil bodies are known to function as storage compartments for lipids. However, the physiological function of leaf oil bodies is unknown. Here, we show that leaf oil bodies function as subcellular factories for the production of a stable phytoalexin in response to fungal infection and senescence. Proteomic analysis of oil bodies prepared from Arabidopsis (Arabidopsis thaliana) leaves identified caleosin (CLO3) and alpha-dioxygenase (alpha-DOX1). Both CLO3 and alpha-DOX1 were localized on the surface of oil bodies. Infection with the pathogenic fungus Colletotrichum higginsianum promoted the formation of CLO3- and alpha-DOX1-positive oil bodies in perilesional areas surrounding the site of infection. alpha-DOX1 catalyzes the reaction from alpha linolenic acid (a major fatty acid component of oil bodies) to an unstable compound, 2-hydroperoxy-octadecatrienoic acid (2-HPOT). Intriguingly, a combination of alpha-DOX1 and CLO3 produced a stable compound, 2-hydroxy octadecatrienoic acid (2-HOT), from alpha-linolenic acid. This suggests that the colocalization of alpha-DOX1 and CLO3 on oil bodies might prevent the degradation of unstable 2-HPOT by efficiently converting 2-HPOT into the stable compound 2 HOT. We found that 2-HOT had antifungal activity against members of the genus Colletotrichum and that infection with C. higginsianum induced 2-HOT production. These results defined 2-HOT as an Arabidopsis phytoalexin. This study provides, to our knowledge, the first evidence that leaf oil bodies produce a phytoalexin under a pathological condition, which suggests a new mechanism of plant defense. PMID- 24214538 TI - Conservation by native peoples : Prey choice in a depleted habitat. AB - Native peoples have often been portrayed as natural conservationists, living a "balanced" existence with nature. It is argued that this perspective is a result of an imprecise operational definition of conservation. Conservation is defined here in contrast to the predictions of foraging theory, which assumes that foragers will behave to maximize their short-term harvesting rate. A behavior is deemed conservation when a short-term cost is paid by the resource harvester in exchange for long-term benefits in the form of sustainable harvests. An example of the usefulness of such an operational definition is presented using data on patch and prey choice decisions of a group of subsistence hunters, the Piro of Amazonian Peru. Results indicate that the area around the Piro village is depleted of prey, and that hunters allocate more time to patches where return rates are highest. This response is consistent with both a conservation strategy and foraging theory. Contrary to the expectation of the conservation strategy, however, hunters do not restrain from pursing opportunistically encountered prey in the depleted areas. The implications for conservation policy are briefly discussed. PMID- 24214537 TI - A guide for the design of evolve and resequencing studies. AB - Standing genetic variation provides a rich reservoir of potentially useful mutations facilitating the adaptation to novel environments. Experimental evolution studies have demonstrated that rapid and strong phenotypic responses to selection can also be obtained in the laboratory. When combined with the next generation sequencing technology, these experiments promise to identify the individual loci contributing to adaption. Nevertheless, until now, very little is known about the design of such evolve & resequencing (E&R) studies. Here, we use forward simulations of entire genomes to evaluate different experimental designs that aim to maximize the power to detect selected variants. We show that low linkage disequilibrium in the starting population, population size, duration of the experiment, and the number of replicates are the key factors in determining the power and accuracy of E&R studies. Furthermore, replication of E&R is more important for detecting the targets of selection than increasing the population size. Using an optimized design, beneficial loci with a selective advantage as low as s = 0.005 can be identified at the nucleotide level. Even when a large number of loci are selected simultaneously, up to 56% can be reliably detected without incurring large numbers of false positives. Our computer simulations suggest that, with an adequate experimental design, E&R studies are a powerful tool to identify adaptive mutations from standing genetic variation and thereby provide an excellent means to analyze the trajectories of selected alleles in evolving populations. PMID- 24214539 TI - Extinction and descent. AB - The probability of lineal extinction is sensitive to all the moments of the reproductive success probability distribution. In particular, high variance in reproductive success is associated with high probability of lineal extinction. Where male variance in reproductive success exceeds female variance, strictly patrilineal lines of descent will become extinct more rapidly than strictly matrilineal lines of descent. Patrilineal genealogies will be expected to be shallower and broader than matrilineal genealogies under such conditions. Potential implications of this genealogical asymmetry for human descent systems include the greater information content of patrilineal kinship reckoning compared with any other unilineal system and the greater effectiveness of patrilineal kinship as a vehicle for corporate action. PMID- 24214541 TI - The family in a changing world : A prolegomenon to an evolutionary analysis. AB - Increasing numbers of young mothers in the work force, more and more children requiring extrafamilial care, high rates of divorce, lower rates of remarriage, increasing numbers of female-headed households, growing numbers of zero-parent families, and significant occurrences of child maltreatment are just some of the social indicators indicative of the family in a changing world. These trends and their consequences for children are described and then examined from the perspectives of microeconomic theory, the relative-income hypothesis, sex-ratio theory, and one form of modernization theory. The paper concludes with a preliminary examination of the added explanatory power provided by evolutionary theory. PMID- 24214540 TI - Environmental tracking by females : Sexual lability. AB - Human females are generally reserved in their sexuality, in keeping with their heavy investment in reproduction. Males tend to be less reserved. Relative to males, however, females demonstrate more variability in sexuality and are more likely to inhibit or express high levels of sexuality. The heightened variability may in part originate with genetic mechanisms that predispose females toward greater variability (the Lyon hypothesis). Menarche, menstrual cycles, menopause, food reactions, responses to living conditions, reactions to cultural factors, and responses to sexual stimuli and potential mates are unique to or are more variable among females than males. There is a correlation between the variation expressed and female reproductive potential-females tend to shift dramatically from sexual inhibition to sexual expression. Females apparently track the quality of the environment and link their sexuality to reproductive opportunities. Successful male reproduction depends less on quality environments and more on the availability of females. In short, females track the environment; males track the females. PMID- 24214542 TI - The addition of 2,2,2-trifluoroethanol prevents the aggregation of guanidinium around protein and impairs its denaturation ability: a molecular dynamics simulation study. AB - TFE, 2,2,2-trifluoroethanol, and guanidinium (Gdm(+) ) are two typical osmolytes. A great number of experimental and theoretical studies have shown that TFE and Gdm(+) can accumulate on protein surface and thus exert their effects on protein structure in their respective solutions. Their accumulation manners are, however, different: the hydrophobic property of TFE makes its accumulation more preferential around hydrophobic side chains than other types whereas Gdm(+) prefers to stack strongly against the planar side chains but only weakly binds to the hydrophobic groups. The present molecular dynamics simulation study shows a novel test to investigate the combined effects of TFE and Gdm(+) on protein structure in mixed guanidinium/TFE solution. The results indicate that the accumulation of TFE is more competitive than Gdm(+) in either GdmSCN/TFE or GdmCl/TFE solution. The preceding accumulation of TFE around protein surface limits the approach of Gdm(+) and water to protein. As a result, the hydrogen bonding between Gdm(+) and water to protein is highly forbidden and the secondary structure stability of protein is strongly enhanced. In contrast, without the presence of TFE, the protein structure is largely denatured in similarly concentrated GdmSCN or GdmCl solution. PMID- 24214544 TI - Cognitive masking in rapid sequential processing: The effect of an emotional picture on preceding and succeeding pictures. AB - This experiment assessed the effect of an emotional pictorial input on the processing of preceding and succeeding pictorial inputs. Thirty-nine individual pictures were successively presented for 165 msec, with a 500-msec dark interval between each item. The 20th input item was either an emotional or a neutral picture; the remaining 38 items were neutral sketches. Postinput recognition data indicated a processing disruption of several pictorial items following the emotional as compared to the neutral input and a possible processing disruption of the item immediately preceding the emotional stimulus. The outcome suggests nonindependence in the processing of separate picture inputs in rapid sequential presentations. PMID- 24214543 TI - Overexpression of MTA1 promotes invasiveness and metastasis of ovarian cancer cells. AB - AIM: To investigate the effect of metastasis-associated gene MTA1 on proliferation and invasion potential of ovarian cancer cell line A2780. METHODS: The eukaryotic expressing vector pcDNA3. 1-MTA1 was introduced into A2780 cells by gene transfection in vitro. The MTA1 mRNA and protein level in cancer cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively. The growth activities of cancer cells were detected by trypan blue stain method. The clone formation assay in soft agar was used to observe the proliferation of cancer cells. Wound healing assay and Transwell assay were used to evaluate migration and invasion abilities of cancer cells. And the protein level of bcl-xL in ovarian cancer cells was measured by immunohistochemistry and western blot. The TUNEL assay was performed to study the apoptosis of tumor cells. RESULTS: Seventy-two hours after transfection, the MTA1 expression increased significantly (P < 0.01). The up-regulation of MTA1 did not affect the growth activities of cancer cells (P > 0.05), but it promoted clone formation, migration and invasion abilities of cancer cells (P < 0.01). The cellular expression of bcl-xL increased 65.22 %, with a PI value of (71.64 +/- 5.96) %. With the up-regulation of MTA1 and bcl-xL level, the apoptotic rate of A2780 cell was decreased. CONCLUSIONS: MTA1 gene plays an important role in progression and metastasis of ovarian cancers, which provides an ideal strategy for gene therapy of ovarian cancers. PMID- 24214545 TI - Memory for noun pairs in the same or different underlying strings. AB - A number of studies have shown that children learn noun pairs faster when they have been presented in a noun-verb-noun context than when they are presented in a noun-conjunction-noun context. Suzuki and Rohwer (1969) hypothesized that the underlying strings of sentences correspond to memory units, making it easier to recall two nouns from the same underlying string than from two different underlying strings. They reported that data from fifth graders supported this hypothesis but that data from college students did not. The experiments reported here were done to determine whether the hypothesis would be supported (a) if the test rate were faster than that used by Suzuki and Rohwer or (b) if sentences longer and more complex than those used by them were employed. The recall data accorded with some predictions derived from the hypothesis. However, data from Ss' posttraining reports on how they learned the pairs suggest that Ss, particularly adults, often made up their own strings rather than using those provided, and raise the question of the adequacy of Suzuki and Rohwer's procedure for testing this hypothesis, particularly in adults. PMID- 24214546 TI - Relationship of visual and name similarity of visually presented letters. AB - Pairs of letters were orthogonally varied with regard to the degree of their visual and name similarities. Each pair was repeatedly presented, alternating with a masking field, until the S gave an identification response. When similarity is high for one feature, the number of correct identifications increases as an inverse linear function of similarity of the other feature. When visual similarity is low, correct identifications increase as a direct linear function of name similarity. However, when name similarity is low, correctddentifications do not vary consistently with visual similarity. The results at high similarity of one feature are interpreted as a reflection of encoding processes, while the results at low similarity levels of the visual feature are interpreted as a reflection of decoding into response form. PMID- 24214547 TI - Retrieval difficulty and subsequent recall. AB - The notion that difficult initial retrieval facilitates subsequent recall was tested in a situation similar to Brown and McNeill's (1966) tip-of-the-tongue (TOT) paradigm. After 50 trials, Ss were unexpectedly asked to recall all the target words. It was found that words retrieved with difficulty in the definition session were relatively well recalled in the final test. Further analyses revealed that the critical factor for good recall was the presence of a TOT state, or a strong feeling of knowing the word, during initial retrieval. An explanation in terms of activation of the word's attributes was suggested. PMID- 24214548 TI - Letter identification in relation to linguistic context and masking conditions. AB - With a two-choice detection procedure, identifiability of signal letters was determined in backgrounds of words, nonword letter strings, or homogeneous noise characters. Under high performance conditions of exposure duration and pre- and postmasks, there was a substantial advantage in identifiability of letters presented alone over letters embedded in words; under low performance conditions there were generally no differences between the two types of context, but some interactive effects appeared involving particular letters with serial position and type of background. No differences were obtained between word and nonword contexts. The disparities between these findings and those reported by Reicher (1969) and Wheeler (1970) may be related to the more complete elimination under the present procedures of effects of redundancy on response selection. PMID- 24214549 TI - Effects of information relevance on decision making in complex environments. AB - Previous research based on predictions of complexity theory has often varied information load and measured characteristics of group decision making. A reinterpretation of related data on success and failure effects suggests that the obtained load effects may be confounded by simultaneous variation of information load and information relevance. To begin studying the separate effects of the two variables, information load was held constant at the previously determined optimal level and information relevance was varied as a proportion of load. It was found that integrated decision making (a complex decision response) was modified by changes in information relevance; but that respondent decision making and information search (simple decision responses) did not change. The results were tentatively interpreted to suggest that complex decision making varies with relevance, while simple decision making varies with information load. It was suggested that complexity theory might be correspondingly modified. PMID- 24214550 TI - Self-perception and characteristics of premanipulation attitudes: A test of Bem's theory. AB - In a study to provide evidence for the assumption of self-perception theory that premanipulation attitudes are not salient to postmanipulation phenomenology, Bem and McConnell (1970) performed two forced-compliance experiments. One experiment was a typical forced-compliance experiment in which Ss indicated their postmanipulation attitudes. In the other experiment, the Ss were asked to recall their premanipulation attitude after the essay writing task. It was found that the recall ratings were essentially the same as the postmanipulation attitude ratings. The present study was a partial replication of the Bern and McConnell experiment. The results of this study indicate that premanipulation attitudes are salient to the postmanipulation phenomenology of Ss for whom these attitudes are highly relevant. PMID- 24214551 TI - Learning effects in information integration: Manipulation of cue validity in an impression formation task. AB - In Stage 1, Ss predicted whether the majority of students in a previous study liked or disliked each of a series of hypothetical persons described by pairs of personality trait adjectives. One trait within each pair was highly polarized on a social desirability dimension, and the other was highly polarized on an intellectual desirability dimension. In Stage 2, new person descriptions were presented and Ss either predicted likabihty ratings for the reference group or gave their own personal ratings. Responses on Stage 2 varied as a function of feedback mampulations on Stage 1. The effect of feedback was to increase the relative weight of the dimension associated with reinforcement on Stage 1. This effect was more pronounced for Ss predcting the ratings of the reference group on Stage 2 than for Ss making personal ratings. These results illustrate how the weighting of information in an integration task can be manipulated through reinforcement contingencies. PMID- 24214552 TI - Obedience as a function of experimenter competence. AB - The purpose of this study was to investigate obedience to an E's commands as a function of E competency. Based upon Orne's (1962, 1969) discussion of the demand characteristics inherent in the typical aggression study, it was hypothesized that E incompetence would decrease S obedience. Competence was manipulated by: (1) presenting some Ss with a nervous and inexperienced E, and (2)"accidentally" killing the victim (a rat) midway through the experiment. Thirty-two undergraduate female Ss participated in the experiment-supposedly a study on the physiological effects of stress. Obedi6nce was operationalized as the difference, in simple reaction time, between trials on which Ss were told that their response might result in shock to the rat and trials on which they were told that their response might save the rat from shock. Significant differences in obedience were obtained between competent and incompetent E conditions, and a significant "kill" effect was found in the competent E conditidn. The results of this study suggested that the extreme acts of obedience observed in the laboratory (e.g., Milgram, 1963) occur only when E is perceived as competent. This finding imposes limits on the generalizability of laboratory studies of obedience. PMID- 24214553 TI - The time required to prepare for a rotated stimulus. AB - Average time required to determine whether an alphanumeric character was presented in its normal version or as its mirror image increased from 500 msec to 1,000 msec as its angular departure from upright increased from 0 to 180 deg. However, when Ss already knew the identity of the upcoming character and when advance information as to its orientation was available for 1,000 msec, this reaction time was reduced to about 400 msec regardless of the orientation of the test stimulus. In this case, Ss claimed that they could prepare for the rotated stimulus by imagining the normal version of the designated character rotated into the indicated orientation and that they could then rapidly test for a match against the ensuing stimulus. PMID- 24214554 TI - Sex composition and group performance in a visual signal detection task. AB - Forty-eight Ss (24 males, 24 females) were run in groups of 4 on 720 trials of a 16-alternative forced-choice visual signal detection task requiring both individual and group decisions. Four types of groups were formed: all male, all female, mixed-alternate (seated in the order male-female-male-female), and mixed adjacent (seated in the order male-male-female-female). There were no differences in performance between all-male and all-female groups, but mixed-sex groups had poorer performance, with mixed-adjacent groups having significantly lower sensitivity than homogeneous-sex groups. The results were interpreted as indicating that heterogeneity of groups with regard to sex interacts with seating pattern in affecting performance, probably due to the formation of information coalitions between like-sex group members when the seating pattern encourages such coalitions. PMID- 24214555 TI - Recognition memory and the recall of spatial location. AB - It is argued that memory for events should depend on the ability to recall their attributes. Two experiments suggest that this is so for the attribute of spatial location. When words presented in spatial arrays were later re-presented in a joint test of recognition memory and location recall, it was found that the surer one's recognition, the greater the accuracy of location recall. Instructions to attend to a word's location resulted in poorer recognition memory and marginally poorer location recall than were obtained when location was "incidentally" learned. Finally, when words were presented in color as well as in space, recognition memory was best when both attributes were recalled, was better when only location, was recalled than when only color was recalled, and was poorest when neither attribute was recalled. PMID- 24214556 TI - Effect of forget instructions with and without the conditions for selective search*. AB - A PA probe experiment was conducted to determine whether a mechanism other than selective search is involved in the Only effect of directed forgetting. To accomplish this, a small number of trials which tested all pairs in the list successively ("all" trials) were intermixed with the standard single-probe trials. On "single" trials, both pretest mechanisms and selective search may operate, but on "all" trials, selective search was eliminated. The analysis compared the Only effect and intrusion data under these two conditions and examined the fate of to-be-forgotten (TBF) recall on "all" trials. The evidence confirmed the major role of selective search in producing the Only effect. It was concluded that if a pretest mechanism was operative, it did not have the properties of a voluntary forgetting mechanism and it had only a small effect on the first half of the list. PMID- 24214557 TI - Attention and the measurement of perceptual learning. AB - Novel and familiar letters were presented to Ss under conditions which controlled momentary attention states. The latencies of letter matching for the novel and familiar letters did not differ when Ss were expecting the particular letters which were presented. However, latencies to the two types of letters differed significantly when Ss were not expecting the particular letters which were presented. Additional exposures significantly reduced this difference, thereby generating a perceptual learning curve in terms of response latency. The main findings were interpreted in terms of a model of perceptual processing which involves mechanisms for hierarchical coding, selective attention, and automatic processing. PMID- 24214558 TI - The interaction of perceptual processes and ambiguous sentences. AB - General principles of speech perception resolve several experimental conflicts about whether listeners interpret one or all meanings of an ambiguous sentence We argue that during all ambiguous clause, both meanings are processed, but immediately after the clause over, it recoded with only one meaning retained This model resolves the apparently conflicting results of previous experimental, it also predicts that underlying structure ambiguity m incomplete clauses increases Comprehension time In complete clauses, ambiguity does not increase relative comprehension time; it mayreduce comprehension time for ambiguities whose interpretations are perceptually distinct in those tasks where either meaning is appropriate Two new experiments offer preliminary confirmation of these predictions. PMID- 24214559 TI - I recognize your face but I can't remember your name: Further evidence on the tip of-the-tongue phenomenon. AB - Fifty faces of "famous" persons were used as stimuli to precipitate the tip-of the-tongue (TOT) experience. Results showed that Ss in TOT states searched for target's name by locating first his profession, where he was most often seen, and how recently. Ss also had accurate knowledge of the initial letters of target names, initial letters of similar sounding names, and numbers of syllables in target names. It was concluded that TOT states for to-be-remembered names are retrieved from semantic and episodie memory systems on the basis of verbal and imaginal encodings. PMID- 24214560 TI - Semantic and associative factors in probability learning with words. AB - Using a probability-learning technique with a single word as the cue and with the probability of a given event following this word fixed at .80, it was found (1) that neither high nor low associates to the original word and (2) that neither synonyms nor antonyms showed differential learning curves subsequent to original learning when the probability for the following event was shifted to .20. In a second study when feedback, in the form of knowledge of results, was withheld, there was a clear-cut similarity of predictions to the originally trained word and the synonyms of both high and low association value and a dissimilarity of these words to a set of antonyms of both high and low association value. Two additional studies confirmed the importance of the semantic dimension as compared with association value as traditionally measured. PMID- 24214561 TI - Encoding differences in recognition and recall. AB - After practice consisting of the free recall of five blocked categorized lists, Ss were presented a sixth list and then unexpectedly tested for recognition. After practice at recognition of the same five lists, Ss were unexpectedly tested for recall following presentation of the sixth test. Recognition performance was superior when items were encoded in anticipation of a recognition test. Intracategory serial position functions for Ss anticipating recall tests were different from those anticipating recognition tests regardless of the retention test employed. The role of control processes in recall and recognition testing is discussed. PMID- 24214562 TI - Short-term retention of superimposed and of spatially distinct multiletter visual arrays. AB - On each trial, Ss attempted to retain a series of five visually presented letters while concurrently "shadowing" (repeating aloud) a rapid series of aurally presented letters. If serial-position accuracy is ignored, they were able to store more than only the last letter of a typical series, even though all five letters appeared on the same screen, and that performance was superior to the retention of five auditorily presented letters. Together, these findings suggest that a form of visual storage might have been employed for the retention of visual stimuli and, specifically, one that was relatively immune to erasure as compared to "iconic" storage. In further support of that hypothesis, retention of such visual series as measured by free-recall accuracy was not inferior to that of five letters, each of which was presented on a separate screen. PMID- 24214563 TI - Failure to find a syllabic effect in number naming. AB - Experiment I replicated the number-naming studies of Eriksen, Pollack, and Montague (1970) and Klapp (1971) but failed to find consistent evidence of a syllabic effect in naming latencies. Experiment II employed a different set of numbers to investigate sources of confounding in the original stimuli. Again, no syllabic effect was obtained. Both studies provided some evidence that the decades are processed faster. PMID- 24214564 TI - The concreteness of attributes in concept learning strategies. AB - Ss were presented with conjunctive concept learning tasks using geometric stimuh in two experiments and using combinations of abstract characteristics in two other experiments. Evidence indicated that the conjunctive hypotheses for geometric stimuli were not mediated by component values but were sampled as unitized wholes. In contrast, conjunctive hypotheses for abstract attributes were sampled via independent combinations of component values. The differential processing was not found to be associated with the variation of stimuli on the verbal-nonverbal dimension. PMID- 24214565 TI - Search reaction time for single targets in multiletter stimuli with brief visual displays. AB - The same set of Ss was run In an LT (single late target letter followed an earher multiletter display) and an ET (single early target preceded a later multiletter display) condition. On one-half the trials, the multiletter set included the target. and on the other half, the target was absent. The task of S was to push the "yes" ("no") button if the target was present (absent), and reaction times were recorded. The most plausible processing model assumed that LT comparisons took place in a verbal-acoustic store and that ET comparisons took place in a visual store. It further assumed that processing within these stores was self terminating, with rates that differed on "same" and "different" comparisons and which changed as the multiletter set increased. Classes of serial and parallel models that are falsified or supported by the present and similar data are discussed. PMID- 24214566 TI - A detailed examination of mediation in PA learning. AB - This paper reports a single experiment in which verbal and imaginal mediators were compared in paired-associate learning. Pair concreteness and delay of recall (immediate vs 1-week delay) were also manipulated. The dependent variables included the latencies of mediator discovery and mediator production, response recall, mediator recall, and recall latency. A variety of differences between verbal and imaginal codes were found in the dependent measures. In addition, a profound effect of immediate recall on subsequent recall was discovered. The results are discussed in terms of the differences between the two modalities of memory. PMID- 24214567 TI - On catching on to idiomatic expressions. AB - These experiments concern the comprehension of idiomatic expressions. The hypothesis was that there are distinct idiomatic and literal modes of processing sentences. In two experiments, 414 undergraduates read a series of sentences containing either literal or idiomatic ambiguities and then a test which had both a literal and an idiomatic meaning. Ss recorded, which meaning they perceived first. Taken together, the experiments indicate that inducing a set to perceive idioms can increase the proportion of people seeing the idiomatic meaning of test sentence first and a set to perceive literal meanings can reduce this proportion compared to a no-set baseline. Since the procedures to induce set did not involve grammatical or semantic information relevant to comprehension of the test sentence, these results suggest the existence of distinct literal and idiomatic processing strategies. PMID- 24214568 TI - Remembering operations. AB - Two commonplace assumptions about encoding are that sentences are encoded and recognized on the basis of their semantic features primarily and that information regarding form features such as typography is typically ignored or discarded. These assumptions were tested m the present experiment where, within a signal detection paradigm, S sorted sentences according to whether he had seen them before or not (old vs new) and, if they were old, whether their reappearance was in the same typography as on the first occurrence or a different one. Of the two typographies, one was familiar and the other unfamiliar. Results show that a considerable amount of information regarding surface features is stored for many minutes and that ease of initial encoding is inversely related to likelihood of subsequent recognition: sentences in the unfamiliar typography were remembered better. The results are probably not due to time spent encoding; control tests suggest that time spent encoding a difficult typography does not by itself increase recognition of the semantic content embodied in the typography. Other control tests show that pictorial features or images of the sentences play no significant role in their subsequent recognition. One interpretation of the results is that the analytic activities or cognitive operations that characterize initial acquisition play a significant role in subsequent recognition. PMID- 24214569 TI - An adding result in impression formation. AB - Ss were presented with a highly polarized piece of information, followed by a same-signed moderately polarized piece of information, and were asked whether the second piece of information led them to like the person describedmore, less, or just the same. The obtained percentage ofadding responses was 65%; that is, most of the responses indicated that Ss impression of the person described became more polarized following addition of moderately polarized information (p <.001). More adding was obtained for negatively than for positively evaluated adjectives (p <.05). PMID- 24214570 TI - Confidence ill stimulus predictions and choice reaction time. AB - In two choice reaction time (RT) experiments, a stimulus prediction and a confidence judgment in the prediction preceded each occurrence of one of two stimulus alternatives. Ss identified each stimulus presentation by pressing a left-hand or right-hand telegraph key. In Experiment I the source of the stimulus predictions and confidence estimates was varied between groups of 20 Ss. For each condition, RT to correctly predicted stimuli was an inverse function of prediction confidence. Following incorrectly predicted stimuli, RT was not reliably influenced by confidence when S gave both predictions and confidence judgments; but RT to incorrectly predicted stimuli was an increasing function of confidence when E verbalized the predictions and confidence estimates or when S predicted and E indicated confidence. In Experiment II Ss made predictions and the validity of Es confidence estimate was manipulated between Ss. When Es confidence was perfectly related to the probability of a correct prediction, choice RT to nonpredicted stimuli was inversely related to confidence. However, choice RT to nonpredicted stimuli was not affected by prediction confidence when Es judgments were random. PMID- 24214571 TI - Organization and long-term memory search. AB - A recognition RT paradigm was used to assess a number of plausible search strategies in LTM for categorized lists. List length was determined by factorially combining two, three, or five categories with two, three, or five words per category, and test items could be one of four types: (1) positive, (2) a repeated positive, (3) a related negative, or (4) an unrelated negative. It was found that RT increased linearly with category size for both positive and related negatives (about 30-40 msec/item); whereas the increase was much smaller for the unrelated negatives, especially for three and five categories (about 9 msec/item). With an increase in the number of categories, RT increased at the rate of about 40 msec/category for all three test items. A theory of .high-speed scanning for categorized material was proposed in which a serial and exhaustive search of the categories, is first undertaken. If a positive category match is found, a serial and exhaustive search within the contents of the positive category is initiated; if no category match is found, the search is simply terminated. Some evidence was presented that categories recently probed may provide for a short-circuiting of the category search. PMID- 24214572 TI - The effect of stimulus complexity on retrieval of information frown memory. AB - Eighteen Ss performed an item recognition task involving memorized lists of one, two, and three nonsense forms at one of two levels of stimulus complexity. Analysis of RT-set size functions and serial position functions suggested that (a) when the memorized list consisted of simple figures, Ss engaged in a serial exhaustive search of items stored in memory prior to responding and (b) when the memorized items were complex, an increase in set size was accompanied by a change in search strategy from a backward self-terminating search to a random self terminating search. PMID- 24214573 TI - Mental set and mental arithmetic. AB - State University of New York, Buffalo, New York 14226 Ss performed mental arithmetic problems in which they added, subtracted, or multiplied two one-digit numbers. The presentation order of the operator symbol and the digits was varied. With three possible operators, presentation of the operator prior to the digits (OD) led to faster RTs. With two possible operators, the opposite order (digits prior to operator, DO) led to faster RTs, because RTs in the OD condition were unaffected by the number of possible operators. These results are discussed in terms of the trade off between accessing active memory for a small number of items in the DO condition vs retrieving information from relatively large tables in long-term memory in the OD condition. PMID- 24214574 TI - Recoding processes in recognition: Some effects of presentation rate. AB - Character classification time was studied in a situation in which Ss sometimes had to decide whether a probe item was a translation of a remembered item according to a previously learned translation scheme. When translation between probe and remembered items was necessary, the rate at which the to-be-remembered items had been presented affected the form of the memory-scanning functions. This result seemed to contradict Cruse and Clifton's (1973) hypothesis that Ss translated all remembered items into the form of the probe after the probe was presented. An alternative model claimed that, when time permits, Ss translate to be-remembered items into their alternate form at the time of presentation and scan the resulting translated items at a relatively slow rate if the probe matches them in form. If Ss are unable to translate the to-be-remembered items when they are presented, they resort to the strategy of translating the probe item into the form in which the remembered items had been presented. PMID- 24214575 TI - Memory for modality of presentation: Within-modality discrimination. AB - Two experiments demonstrated that Ss are capable of making within-modality memory discriminations in both visual and auditory modalities. In Experiment I Ss studied mixed lists of pictures and labels representing common objects and were subsequently required to judge whether the original presentation was pictorial or verbal The high level of performance achieved on this task was unaffected by degree of categorical relatedness of items within method of presentation or by instructions to produce visual images when items were presented verbally. In Experiment II Ss demonstrated the ability to remember whether a sentence was originally presented by a male or a female speaker. Some strategies by which within-modality discrimination in memory might be accomplished are discussed. PMID- 24214576 TI - From projected species distribution to food-web structure under climate change. AB - Climate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food-web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food-web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080-2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large-scale impacts of climate change on marine food-web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems. PMID- 24214577 TI - Trienamines derived from interrupted cyclic 2,5-dienones: remote delta,epsilon C=C bond activation for asymmetric inverse-electron-demand aza-Diels-Alder reaction. PMID- 24214578 TI - B-type natriuretic peptide levels in preterm neonates with bronchopulmonary dysplasia: a marker of severity? AB - RATIONALE FOR THE STUDY: B type natriuretic peptide (BNP) is a hormone released in response to stretching of the ventricular wall. The role of BNP as a biomarker of bronchopulmonary dysplasia (BPD) has not been clarified. OBJECTIVE: To determine if plasma BNP concentrations correlate with the severity of BPD. METHODS: This prospective observational case control study included 60 preterm infants (<=32 weeks); 27 infants had no/mild BPD, 19 had moderate and 14 had severe BPD. BNP levels were measured at 36 +/- 2 weeks PMA or within a week of discharge home. Groups were compared using Mann-Whitney's U-test, Kruskal-Wallis, and bivariate regression. RESULTS: Median (IQR) plasma levels of BNP in infants with moderate/severe BPD infants (n = 33) were higher as compared to those with no/mild BPD (n = 27); 27.1 (12.1-43.5) pg/ml versus 9.3 (6-18.5) pg/ml; P < 0.05 (Mann Whitney U). Median (IQR) BNP levels in infants with severe BPD (n = 14), 43.5 (28.4-189) pg/ml differed significantly from levels in those with moderate (n = 19), 22.8 (10.3-27.7) pg/ml; mild (n = 16), 11.5 (6.6-44.5 pg/ml); or no (n = 11), 8.1 (5-12.6 pg/ml) BPD (P < 0.001 Kruskal-Wallis). Based on receiver operating characteristic curves, BNP > 24.4 pg/ml at 36 +/- 2 weeks PMA or discharge home was 85.7% sensitive and 76.1% specific for severe BPD. CONCLUSIONS: An elevation in plasma BNP was significantly associated with severe BPD. We speculate that plasma BNP measurement in infants with BPD may aid in risk stratification and further targeted therapies. PMID- 24214579 TI - Hemiconvulsion-hemiplegia-epilepsy syndrome with 1q44 microdeletion: causal or chance association. AB - Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. Exact pathogenesis is not clear. Here we are describing a 3 year-old girl with HHE syndrome with cytogenetic microarray (CMA) showing deletion of 1.8 Mb in 1q44 region. Along with HHE syndrome, the patient also had global developmental delay, subtle facial dysmorphism, and preaxial polydactyly. Clinical phenotype of 1q44 microdeletion syndrome is quite variable. Main clinical features are microcephaly, seizures, and abnormality of corpus callosum. We compared the patient's phenotype with other patients in 10 previously published papers of 1q44 microdeletion syndrome. HNRNPU and FAM36A are two important genes in the deleted region. HNRNPU gene mediate long range control of SHH gene which is likely explanation of preaxial polydactyly in the present patient. HHE may be a chance co-occurrence. PMID- 24214580 TI - Significance of the learning curve in left atrial appendage occlusion with two different devices. AB - OBJECTIVE: To evaluate the impact of learning on outcome with use of two different left atrial appendage (LAA) occlusion devices. BACKGROUND: Two self expanding devices, the Watchman and the Amplatzer Cardiac Plug (ACP), have been used for LAA occlusion in the last few years. It has been demonstrated that complications associated with implantation decrease in frequency with operator experience. However, the role of operator experience has not been compared across the two device types. METHODS: The study comprises 31 consecutive patients who underwent LAA occlusion. We compare the first 10 patients in whom an ACP was implanted with the subsequent eleven patients who underwent ACP implantation and with 10 cases where a Watcthman device was implanted. The composite safety end point comprised procedure-related events and excessive bleeding events. We also performed 3 months echocardiographic and clinical follow-up. RESULTS: There were not significant differences in the basal clinical and echocardiographical characteristics across the three groups. Cardiac complications only occurred in the ACP initial experience group (9% vs. 0% vs. 0% P = 0.04). Echocardiographic and clinical follow-up at 3 months was completed in all patients. No significant residual leak was detected. One patient in the ACP initial experience group developed a thrombus on the device. One patient in ACP late experience presented an ischemic stroke. CONCLUSIONS: Complications associated with LAA occlusion cluster early in the peri-procedural period and significantly decrease in frequency with operator experience. Initial experience gained with one of device may improve outcome with use of alternative LAA occlusion devices. PMID- 24214581 TI - Major abdominal cancer resections in cirrhotic patients: how frequent is postoperative hepatocellular decompensation? AB - BACKGROUND: The reported incidence of postoperative liver failure in cirrhotic patients is highly varied with diverse risk factors identified to predict risk, mainly drawn from organ or disease-specific studies. We aimed to assess risk factors for the development of postoperative liver failure in a specific cohort of patients with cirrhosis undergoing abdominal cancer resection. METHODS: From November 2007 to October 2012, 30 cirrhotic patients who underwent curative resection for abdominal cancer were analyzed. The postoperative trends in liver function were followed and the incidence of postoperative liver failure was demonstrated. RESULTS: Among the 30 patients, the tumors were located in the stomach (n = 5), pancreas (n = 5), colon/rectum (6), liver (n = 11), gallbladder (n = 1), and retroperitoneum (n = 2). Eighteen (60 %) patients experienced postoperative liver failure of which 7 (23 %) patients required deviation from the clinical course or management. There was one mortality due to grade C liver failure and hepatorenal syndrome. On multivariate analysis, only age (>55 years) was found to be statistically significant to predict postoperative liver failure (p = 0.024). CONCLUSION: Liver dysfunction remains a major problem during the postoperative phase of major gastrointestinal cancer resections. However, less than one fourth of well-selected patients will develop significant postoperative liver failure. This incidence may be further reduced if the selection is restricted to younger patients. PMID- 24214582 TI - Is superior mesenteric artery reimplantation during surgery for pancreaticoduodenal tumors an underutilized procedure? AB - Resection and reimplantation of the superior mesenteric artery (SMA) as part of a pancreaticoduodenal resection for cancer is rarely performed even in high-volume centers because of the risks inherent in this procedure and the perceived lack of oncological benefit associated with arterial resection during pancreaticoduodenectomy. The role of arterial resection during pancreaticoduodenectomy has recently been reevaluated, and this procedure may be of greater benefit than previously believed in selected patients. It also has a definite role when necessary to resect low-grade pancreatic and peripancreatic malignancies or to salvage intraoperative injury to the SMA. This small case series presents the authors experience with this procedure. PMID- 24214583 TI - Sclerosing encapsulating peritonitis: a case series. AB - Sclerosing encapsulating peritonitis (SEP) is a relatively rare cause of intestinal obstruction characterized by total or partial encapsulation of the small intestine by a thick fibrous membrane and is a difficult preoperative diagnosis. A series of seven cases of SEP is reported. Modalities of preoperative diagnosis along with clinical presentation, operative findings, and histopathology are discussed. PMID- 24214585 TI - Comparison of intravenous pantoprazole with intravenous ranitidine in peptic ulcer bleeding. AB - Following successful endoscopic therapy in patients with peptic ulcer bleeding, rebleeding occurs in 4% to 30% of cases. Rebleeding remains the most important determinant of poor prognosis. The aim of our study is to compare the efficacy of intravenous pantoprazole and ranitidine for prevention of rebleeding of peptic ulcers following initial endoscopic hemostasis. In our study patients who had gastric or duodenal ulcers with bleeding received combined endoscopy therapy with injection of epinephrine and thermocoagulation. Patients with initial hemostasis were randomly assigned to two groups. One group (45 patients) was treated with intravenous pantoprazole, with an initial dose of 40 mg and subsequently with 40 mg every twelve hours during the first three days, followed by 40 mg a day orally. The other group (44 patients) was treated with intravenous ranitidine, with an initial dose of 50 mg and subsequently every eight hours during the first three days, followed by 150 mg ranitidine every 12 h. In all case of rebleeding repeated endoscopy was performed. One patient (2,2%) had rebleeding in pantoprazole group. Bleeding could not be blocked by repeated endoscopic intervention, thus the patient underwent emergency surgery. 6 patients (13,6%) from ranitidine group had recurrence of bleeding. Repeated endoscopy was performed in all these patients: bleeding was stopped in 3 cases endoscopically, other 3 patients were surgically treated urgently as endoscopic hemostasis was not successful. None of the patients died of uncontrolled rebleeding. The frequency of rebleeding was significantly low in the group of pantoprazole compared to ranitidine group (2,2% vs 13,6% P=0,046). There were no statistically significant differences between the groups with regard to need for emergency surgery (2,2% vs 6,8%), the length of hospital stay (6,7+/-3,3 vs 7,4+/-4,3 d) and mortality (0%vs 0%). After endoscopic treatment of bleeding peptic ulcers, intravenous pantoprazole is more effective than ranitidine for the prevention of rebleeding. PMID- 24214586 TI - [Pathogenetic percularities of fetal distress in pregnant women with preeclampsia]. AB - It was performed the investigation of the fetal regulatory systems condition with the heart rate variability method application in 94 women with preeclampsia. It was established that preeclamptic patients had thrombophilia that was accompanied by increased reversible aggregation of platelets in response to low doses of ADP and collagen stimulation. The fetal deterioration in this group was characterized by decreased fetal heart rate variability fractal components with a relative predominance of the central sympathetic control circuit. The augmented sympathetic tone played the significant role in fetal rigid rhythm and decelerations appearance and has formed the fetal myocardium hypoxic injury and the suppressed sinus node response. The usage of semisynthetic diosmin 1 tablet (600 mg) 2 times daily in preeclamptic ladies has a pronounced disaggregant effect and improved fetal autonomic nervous regulation in its projections on hemodynamics. The restoration of the fetal cardiorespiratory synchronization periods has made it possible to consider that diosmine has neuroprotective effect that was directed on the fetal regulatory systems condition optimization. PMID- 24214584 TI - Multifaceted leptin network: the molecular connection between obesity and breast cancer. AB - High plasma levels of leptin, a major adipocytokine produced by adipocytes, are correlated with increased fat mass in obese state. Leptin is emerging as a key candidate molecule linking obesity with breast cancer. Acting via endocrine, paracrine, and autocrine manner, leptin impacts various stages of breast tumorigenesis from initiation and primary tumor growth to metastatic progression. Leptin also modulates the tumor microenvironment mainly through supporting migration of endothelial cells, neo-angiogenesis and sustaining recruitment of macrophage and monocytes. Various studies have shown that hyperactive leptin signaling network leads to concurrent activation of multiple oncogenic pathways resulting in enhanced proliferation, decreased apoptosis, acquisition of mesenchymal phenotype, potentiated migration and enhanced invasion potential of tumor cells. Furthermore, the capability of leptin to interact with other molecular effectors of obese state including, estrogen, IGF-1, insulin, VEGF and inflammatory cytokines further increases its impact on breast tumor progression in obese state. This article presents an overview of the studies investigating the involvement of leptin in breast cancer. PMID- 24214587 TI - Peculiarities of cyclin D1 expression in reproductive and menopausal women with cervical hyperkeratosis. AB - Morphological diagnosis of cervical intraepithelial neoplastic (CIN) lesions sometimes requires an additional study of molecular markers. Cyclin D1 is a key regulatory protein, which regulates cell cycle progression from G1 to S phase. Disruption of G1/S regulatory mechanisms is basic mechanism of HPV mediated malignant transformation of cervical epithelium. The aim of the research was to study the peculiarities of cyclin D1 protein expression in reproductive and menopausal women with cervical hyperkeratosis. We examined cyclin D1 protein expression in 381 reproductive and 233 menopausal women with cyto-colposcopically detected and histologically proved hyperkeratosis, using immunohistochemical method. Monoclonal ready to use (RTU) antibody against cyclin D1 antigen (Dako) was used. Cyclin D1 positivity in <=50% of cells considered as low and in >=50% - as high expression. High expression of cyclin D1 was present in CIN1 of 93,3% reproductive and 66,7% menopausal women, whilst in CINII the high expression was revealed in 53,3% and 43,8% respectively. The weak expression of cyclin D1 was present in only one cases of CINIII, other CINIII cases were all negative. The expression of cyclin D1 protein in cervical intraepithelial neoplastic lesions is not regular, however the overexpression of cyclin D1 is almost always present in CIN1 of reproductive women, in which it might be considered as an additional diagnostic marker. PMID- 24214588 TI - [The influence of the element status on mineralization of dental hard tissues in young children]. AB - Child's organism is a kind of marker of increased sensitivity to environmental conditions. Lack of vital (essential) elements may lead to disease occurrence, caused by deficiency, excess or imbalance of micro- and macro elements in the organism. To assess the level of trace elements content in the human body, the hair is a good informative material as it concentrates trace elements and most fully reflects the level of both toxic and essential elements content. In order to conduct a comparative analysis of the elemental composition of hair in children and assess the relationship between the elemental composition of hair and the state of oral health status, we have examined 28 patients who underwent simultaneous determination of 28 chemical elements in the hair. According to the obtained data, in elemental composition of hair in children of group I, living in the regions with moderate environmental contamination, there was a minimal decrease of essential elements (except Ca), a slight increase of toxic chemical elements - Pb and Cd and decompensated form of dental caries have been observed. Investigation of the second group of children living in environmentally unfavorable regions showed that children with decompensated form of caries prevalence are characterized by the significant reduction of hair essential chemical elements in average of 28- to 56% and by a high content of toxic elements such as Pb, Hg, and Zr. The fact indicates enhanced excretion of essential elements under the influence of heavy metals, which in its turn affects the whole body and dental health. PMID- 24214589 TI - [Experimental basis of a new material for the manufacture of bases dentures]. AB - The author studied the problem of improving the quality of prosthetic removable prostheses through the development of new basic material based on polypropylene copolymer. To this end, we examined the physical and chemical structure and hygienic properties of the produced material. The studies found that the developed material of polypropylene optimal solution for the partial plate denture bases, without flaws acrylic prosthesis and improves the properties of the previously used polypropylene plastics. PMID- 24214590 TI - [Improvement of rosacea treatment based on the morphological and functional features of the skin]. AB - Rosacea - a widespread disease sometimes aleak with severe complications, mainly affecting the skin. Irrational and inadequate treatment leads to chronicity of diseases and psychosocial disadaptation of patients. Lately, a clear upward trend in the number of patients in whom in the process of complex treatment manifestations (with the varying degrees of severity) of impaired barrier function of the skin are observed and they need the protection and restoration of the damaged stratum corneum. In patients with rosacea in order to study the function of the facial skin's horny layer we used the skin analyzer BIA (bioimpedance analysis, which in duration of 6 seconds determines the moisture content, oiliness and the softness of the skin) and significant deviations from the norm (decrease in moisture content, fatness and increased roughness) was revealed. These changes were most clearly pronounced in patients with steroid rosacea. To restore the skin barrier the drug "Episofit A" (Laboratory of Evolutionary Dermatology, France) has been used (1-2 times a day for 6 weeks). Evaluation of treatment efficacy was conducted every 2 weeks by means of a scale from 0 to 5 for parameters of dryness, erythema, peeling and expression of subjective feelings. In accordance with received results, using of Episofit A emulsion, especially on the baskground of long-term treatment with topical steroids, had a pronounced therapeutic effect. Thus, treatment of patients with consideration of morphological and functional features of facial skin, helps to improve the results traditional therapy, and the drug is highly effective means of the new direction in skin care - corneotherapy aimed to reconstruct and protect damaged stratum corneum. PMID- 24214591 TI - [Genetic aspects of atrial fibrillation in coronary artery disease patients]. AB - To examine the relationship I/D polymorphism of the angiotensin-converting enzyme (ACE) gene and polymorphism A1166S of angiotensin II type 1 receptor (AT2R1) gene with the development of atrial fibrillation (AF) in patients with coronary artery disease (CAD), the residents of Kharkiv region. The study involved 318 patients with CAD, of whom 54 (17,0%) patients with CHD and AF were included in group I, 264 (93,0%) patients without AF - in group II. The control group included 35 people without atherosclerotic and morphological changes of spacecraft. Study of ACE gene I/D polymorphism and A1166S polymorphism of AT2R1 gene was performed by polymerase chain reaction (PCR) with electrophoretic pattern of result detection. Established that the AF development in patients with CAD, residents of Kharkiv region was associated with carriage of C allele of AT2R1 gene A1166S polymorphism and the presence of DD genotype of the ACE gene I / D polymorphism. Proved that the risk of AF development in patients with coronary heart disease independently associated with the presence of C allele of AT2R1 gene A1166S polymorphism, hypertension, type II diabetes and obesity. PMID- 24214592 TI - [Ultrasonic diagnosis of functional and organic changes of colon in patients suffering from chronic constipation]. AB - The aim of the study was to define the informative significance of USI in the diagnosis of functional and organic changes in patients suffering from chronic constipation (CC). 96 patients with CC were evaluated and treated. There were 67 women and 29 men (79) aged 33-55 years. 11 patients were in compensated stage of CC, 32 patients were in subcompensated stage, 53 patients-in decompensated stage of CC. Before investigation under USI control a colon was filled with 2 l of physiologic solution heated up to 37o. Sonographically in normotonic type of CC a colonic wall tonus was reserved, no changes in colonic transition were observed, while there is a delay in rectum. In subcompensated stage of atonic type of CC there was observed a noticeable enlargement of colonic diameter in transverse colon, descending colon and also in sigmoid colon. It is likely, that the wall of all portions of colon was thickened. The reduction of height of transverse folds and the increase of distance between them was traced in colon. In spastic type of CC a colonic wall tonus has been increased in all portions, there are spastic segments in colon, the distance of fecal particles' displacement from spastic region is enlarged. It is obviously that for atonic type of CC sonographically it is typical the attenuation of colonic wall tonus in all portions of colon, the reduction of distance of colonic content displacement and also the reduction of height of natural transverse folds and haustra fundus flattening. PMID- 24214593 TI - [Almaty club "KAIRAT" young football players' health]. AB - The aim of the investigation was to study young football players' health. The study was conducted on 161 football players (mean age 12.3) of six children football teams of Almaty club "KAIRAT" during the competition period. It was found that 55,5% of the football players are practically healthy; 18,6% of football players have iron deficiency anemia. 32,6% of football players have caries; 5% of football players have problems of cardiopulmonary system. Investigation reveal, that in a junior sportsman was body weigh surging with downtrend during contest, testify to portability of aerobic load and in childhood unconformable of metabolism' level. This tendency was retain also in the oldest sportsman, this testify to most emulative aerobic load in comparison with junior sportsman. According as the age increases it is emulative load's extension and free occurrence of body weigh subsequent reduction but in the oldest sportsman with prevalence macrosomia. Concurrently with improvement of the anthropometric profile as far as increase of age in soccer players it is forming of a high training level. In spite of lowering of energy resources and the physical load organism's adaptation there are these phenomena. According as the age increases in a soccer player's performance of cardiac and respiratory system are improved. PMID- 24214594 TI - The role of parvovirus in the etiology of somatic pathology. AB - The scope of the present research was to study parvovirus circulation in Tbilisi population and its role in etiology of somatic pathologies. Parvovirus circulation in persons with autism and disorder of the nervous system was examined. Blood of 110 patients was examined. Among them 35 were children (up to 15 years old) and 75 adults, mainly with different somatic pathologies such as mineral metabolism disorder, allergic reactions, cystic fibrosis, cerebral palsy and autism. Almost all the children came from the so called frequently ill category and suffered from disbacteriosis. Among adults, 16 were parents of the ill children, while the rest came with hepatitis, mineral metabolism disorder of different type and psoriasis. Blood serum of 30 adults was taken as an adult control group. Their age varied from 18 to 25 years. 10 children aged 2-15 constituted a children control group. Preventive examination was made and there were practically, absolutely healthy persons. A total of 150 persons were involved in the research. Frequency of parvoviral antibody detection in the ill children and adults is much higher than in healthy individuals. Consequently, positive results for the presence of M and G immunoglobulins in children equals to 54% and 85% respectively. In adults these indicator stand at 24% and 60% respectively. At the same time in 25% and 70% of parents of positive children were found to be positive for M immunoglobulin and G immunoglobulin respectively. Thus our investigation made it clear that parvoviral infection actively circulates in Georgia. The present research did not study manifested parvoviral infection, i.e. 5th disease. If it had than the number of positive results probably would have been much higher. In autistic children presence of parvoviral infection is consistent with the literature data. PMID- 24214596 TI - [Pharmakological characteristic of some amide local anesthetics, currently used in dental clinics]. AB - Along with the brief history of amide local anesthetics development, their most important properties (from the viewpoint of use in clinical dental practice), are also reviewed. In particular, some properties of most commonly used local anesthetics, such as lidocaine, mepivacaine, prilocaine, bupivacaine and articaine are analysed. The most important data concerning pharmacological mechanisms of mentioned anesthetics' action, that cause certain features and peculiarities of their clinical application are given in condensed form. Besides, some precaution measures that must be taken into account in specific clinical cases together with the history and current status of each patient are mentioned as well. PMID- 24214595 TI - beta2-adrenergic regulation of T lymphocites function (in vitro study). AB - The aim of our study was to establish the influence of beta2AR agonists and antagonists on Th1/Th2 subpopulation balance in intact and activated CD4+ T lymphocyte. Jurkat leukemic T cell line was used as a model for studying T cell activation conditions under the influence of beta2AR ligands. As follows from the results of our studies, after the influence of beta2AR agonist isoproterenol on intact Jurkat cells expression of IL-2 was not changed in comparison to control level. Under the PHA-stimulation level of IL-2 production in Jurkat cells increased significantly; isoproterenol caused decrease level of IL-2 expression in the PHA-stimulated Jurkat cells. Adding of beta2AR antagonist propranolol to the Jurkat cells pre-incubated with isoproterenol didn't change expression of IL 2. beta2AR antagonist propranolol induced slight increase of IL-2 expression in PHA-stimulated Jurkat cells pre-incubated with isoproterenol. Neither isoproterenol nor propranolol didn't change intensity of IL-10 expression in intact Jurkat cells. In the PHA-stimulated Jurkat cells level of IL-10 production decreased in comparison to control level. Isoproterenol induced sharp intensification of IL-10 expression in these cells. Propranolol prevented increase of IL-10 expression in the PHA-stimulated Jurkat cells pre-incubated with beta2AR agonist. It was concluded that beta2ARs in dose-dependent manner regulate cytokine profile in intact and mitogen activated CD4+ T lymphocyte and by this way induce dose-dependent alterations of lymphocyte proliferation and immune response. This indicated existence of a link among immune response and sympathetic nervous system activity. PMID- 24214597 TI - [The impact of pregnancy and postnatal period on the development of generalized convulsive activity in experiment]. AB - Interrelation between pregnancy and epilepsy is one of the pressing problems of current neurology. Those mechanisms, which suppress or amplify the seizure reactions in pregnancy, have not been yet determined experimentally. The goal of present work was investigation of impact of gestation and the postpartum period on initiation and development of convulsive reactions in the experimental animal model. Epileptic reactions were significantly suppressed during gestation (2 and 3 weeks). The data showed changes in behavioral reactions and EEG seizure activity. In the period of gestation the development of audiogenic kindling in response to repetitive acoustic stimulation is markedly reduced. This indicates the strengthening of inhibitory processes in the brain. It is supposed that in the period of gestation in rats with genetically determined audiogenic seizures excess of sexual hormones and enhancement of GABA-ergic transmission causes marked reduction of development of audiogenic kindling. PMID- 24214598 TI - Laser induced fluorescence spectroscopy for detection of erlikh adenocarcinoma (a pilot study). AB - Current diagnostic methods, including computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), have not been able to provide accurate diagnosis in early stage disease, either by failing to identify small lesions or accurately differentiating masses as adenoma or cancer. On the other hand, optical spectroscopic techniques examine different types of light tissue interactions and provide biochemical and morphological information that can be used to characterize changes that take place as tissues become diseased. The combined use of intrinsic fluorescence, diffuse reflectance and light scattering spectroscopy yields complementary information which can be used to detect even precancers. The aim of our study was to evaluate the effectiveness of laser examination in diagnose of oral mucosa tumors. This method gives us possibility of precise diagnostic in just few minutes. Our pilot survey has shown the efficacy of using laser induced fluorescence (LIF) spectroscopy for diagnostic oral mucosa pathology. PMID- 24214599 TI - [Reparative osteogenesis of tubular bones in the conditions of violation of water salt exchange]. AB - The purpose of the article was to study the bone reparative regeneration in disorders caused by the dehydration of organism. Studies were conducted on 72 white laboratory young male rats. The structural and metabolic displays of reparative osteogenesis were studied by means of histological research of defected area, morphometry of histological preparations by means of the computer programs "Video Test 5,0" and "Video size 5,0". Quantitative disorders of regenerated cellular composition were found on the 3-rd day. Atypical granulation tissue was found on the 15-th day. The delay of regeneration - on the 24th day. It was concluded that the inhibition of reparative osteogenesis occurred under the influence of dehydration. The strongest impact on the process of bone regeneration was caused by an extracellular dehydration. PMID- 24214600 TI - Ubiquitin in combination with alcohol stimulates proliferative activity of hepatocytes. AB - There are several factors involved in aetiology of Alcoholic Liver Disease. The one of the most important role in regulation of intracellular transformations belongs to ubiquitin proteasome system that is comparably well studied, but less is known about the functions of extracellular ubiquitin. The goal of presented work is to study the effect of extracellular ubiquitin on partially hepatectomized alcoholic liver regeneration. Experiments were carried out on white female rats. Proliferative activity of hepatocytes was determined by colchicine mitotic index and immunohistochemical staining on Ki67. We have shown that in vivo injected extracellular ubiquitin stimulates proliferative activity of hepatocytes in partially hepatectomized alcoholic liver whereas in non alcoholic rats hepatocytes proliferative activity was decreased. The main attraction of the experiment is the combination of alcohol and ubiquitin, as without alcohol ubiquitin inhibits proliferative activity of hepatocytes and blood cells. Further investigation of its action will provide new insights into possible pathway of ubiquitilation involved in stimulation of proliferative activity in alcoholic liver. PMID- 24214601 TI - [Expression of epidermal growth factor receptor and plasmatic level of melatonin in simple and complex endometrial hyperplasia]. AB - The goal of our research was to find the prognostic significance of the epidermal growth factor receptor (EGFR) in the hyperplastic endometrium. Immunohistochemical study of morphological material (endometrial scrap) was conducted in order to reveal the EGFR expression (in 35 patients). The study of consistence of melatonin (universal antiproliferative and anticancerogenic hormone) in patients' blood serum was performed as well (using ELISA method). The numeric data of investigation were processed statistically using the SPSS-12 program and IBM SPSS Statistics, 20. According to received results, the more complicated the type of endometrial hyperplasia is, the stronger EGFR expression is and the more melatonin consistence is reduced in blood plasma. However, sometimes much lower level of melatonin not only in case of complex hyperplasia (with atypia), but also in case of simple hyperplasia (without atypia) was observed. In addition, melatonin consistence is in norm not only in case of simple hyperplasia, but also in case of complex hyperplasia. Also, unimportant reduction of melatonin level is seen in plasma in case of both types of endometrial hyperplasia (without atypia): if, for example, in simple hyperplasia, this slight reduction of melatonin level in plasma is seen in condition of sharp EGFR expression, the same amount reduction of plasmatic melatonin in complex hyperplasia is seen in condition of weak EGFR expression. To sum up: in case of simple endometrial hyperplasia without atypia, reduction of plasma melatonin level should be a bad prognostic indicator and this condition can be followed by transformation of hyperplasia into atypical form; the normal plasmatic level of melatonin in complex endometrial hyperplasia without atypia (in condition of weak EGFR expression) should be a good prognostic indicator; unimportant reduction of plasma melatonin level and in addition, EGFR sharp expression in simple hyperplasia, is probably the sign, that hyperplasia can change and become complex; however, the same indicators of plasma melatonin level (on the background of weak EGFR expression) in complex hyperplasia (without atypia) should not indicate the poor prognosis. PMID- 24214602 TI - [The study of properties of textile wipes "LNR"]. AB - The aim of the research was to investigate the toxicity of textile wipes "LNR". The wipes coated with polymer as well as wipes coated with polymer and drug substance were studied on CBA mice. It was found that both types of "LNR " napkins do not cause any toxic effect, mortality or changes of internal organs of mice in acute and in chronic experiments. The study of the cytotoxic effect of "LNR" wipes according to test of cell survival in tissue culture showed that during contact exposure of the samples on cell wipes "LC" significant inhibition of culture growth observed in sample 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1. PMID- 24214603 TI - Synthesis and evaluation of novel 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives as potential antidepressants. AB - A series of 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives were synthesized and the target compounds were evaluated for their binding affinities at the 5-HT1A receptor and serotonin transporter. Antidepressant-like activities of the compounds were screened using the tail suspension and forced swim tests in mice. Preliminary results indicated that the target compounds exhibited high binding affinities at the 5-HT1A receptor and serotonin transporter, and produced marked antidepressant-like effects. The best example from this study, compound 5, exhibited high binding affinities for the 5-HT1A receptor (Ki = 96 nM) and serotonin transporter (Ki = 9.8 nM). The intrinsic activity of compound 5 showed agonistic property to the 5-HT1A receptor and inhibition of the 5-HT transporter. Furthermore, compound 5 exhibited greater antidepressant efficacy than fluoxetine and showed acceptable pharmacokinetic properties. PMID- 24214604 TI - Immunochemical cross-reactivity ofbeta-naphthoflavone-inducible cytochrome P450 (P450IA) in liver microsomes from different fish species and rat. AB - Antibodies prepared against the major beta-naphthoflavone (BNF)-inducible cytochrome P450 (P450) forms from three species of fish (rainbow trout, Atlantic cod, and scup) well separated in teleost phylogeny, were used to investigate the immunochemical relatedness of liver microsomal P450 in different species of BNF treated fish and rat. Rabbit polyclonal IgG against all three P450s and mouse monoclonal antibodies prepared against scup P450E were employed in this study. Liver microsomes were prepared from BNF-treated specimens of hagfish, herring, rainbow trout, cod, scup, perch, plaice and rat. With Western blotting it was shown that the various antibodies cross-reacted with a protein band in liver microsomes in the P450-region of each of the BNF-treated fish species. The apparent molecular weight of the cross-reacting proteins showed differences within the range 54,000-59,000 daltons. The effects of the different antibodies on the microsomal BNF-inducible 7-ethoxyresorufin O-deethylase (EROD) activity gave inhibition patterns that reflected to a certain extent the phylogenetic relationship of the species investigated. In rat microsomes a protein band of relative molecular mass similar to rat P450c (Mr=54,000) was recognized by all antibodies. In addition, a second band of lower molecular mass was strongly recognized by anti-cod P450c antibodies, and faintly stained with anti-rainbow trout P450LM4b IgG and anti-scup P450E MAb 1-12-3. This band could correspond to rat P450d, the isosafrole-inducible rat isoenzyme. Considering the long separate evolutionary history of some of these fishes (50-200 million years), the results demonstrate that certain antigenic epitopes in the BNF-inducible P450 isoenzymes have been strongly conserved during the evolution of fish species. These conserved epitopes seem however not to be directly involved in the measured EROD activities. Furthermore, the results suggest that the BNF-inducible P450s in fish contain regions with structural similarity to the homologous counterpart that has evolved through gene duplication into a P450 family in mammals containing at least two gene products (the P450IA gene family). PMID- 24214605 TI - The effect of water pH on swimming performance in rainbow trout (Salmo gairdneri, Richardson). AB - A Brett-type respirometer was used to measure the effect of water pH on swimming performance of rainbow trout (Salmo gairdneri). Variations in water pH between 6 and 9 had no measurable effect on maximum aerobic swimming speed. At water pH 4, 5, and 10, however, the critical velocity was only 55, 67, and 61% respectively of that recorded for fish in water of pH 7. Exposure to acid conditions increased coughing and breathing frequency. Acid exposure resulted in a decrease whereas alkaline exposure resulted in an increase in both whole blood and red blood cell pH. Blood gas and acid-base characteristics showed little change during swimming at ~2.0 BL/second, but exhaustive swimming resulted in a marked and immediate drop in blood pH in fish in acid, alkaline and neutral water. The blood acid-base status was restored to resting levels after exercise in neutral and alkaline water, but the acidosis was maintained following exercise in acid water. Fatigue occurred earlier and blood lactate levels increased to a higher level in fish swum to exhaustion in acid or alkaline water, compared with fish in neutral water. PMID- 24214606 TI - The effect of acid water on oxygen consumption, circulating catecholamines and blood ionic and acid-base status in rainbow trout (Salmo gairdneri, Richardson). AB - Chronically cannulated rainbow trout were exposed in acid water (pH 4.0) for 72h. The gill potential was strongly dependent on water pH, being blood side negative in neutral water, but positive in acid water. Catecholamine levels increased irregularly during acid exposure, and the Bohr and Root effects were not completely erased by the effect of catecholamines during acid exposure. Long term exposure to low water pH, although causing an acidosis in the fish, did not suppress resting oxygen consumption. Prolonged exposure to acid conditions, however, resulted in an increase in ammonia excretion. Changes in plasma sodium and chloride were similar to that reported previously for trout exposed to low calcium, acid water. We conclude that exposure of trout to pH 4 soft water, although impairing oxygen transport, does not limit resting oxygen consumption but does reduce the scope for activity. More extreme acid conditions do impair resting oxygen uptake. PMID- 24214607 TI - Effects of diet on amylase expression in the mosquitofish. AB - Diets high in various carbohydrates were fed to mosquitofish,Gambusia affinis holbrooki, to determine the effects on amylase expression. Both amylase activity and amount of amylase protein were used as measures of amylase expression. Fish were fed for 21 days in one experiment, seven days in a second experiment and 24 h in a third. The first experiment compared responses of fish fed on a high starch diet relative to a control diet. The second and third experiments compared responses on four diets relative to the control diet: maltose, starch, glucose, and glucose + cyclic adenosine monophosphate (cAMP). In the first two experiments whole visceral extracts were used. In the third experiment, gut and hepatopancreatic extracts were examined separately. Diet had a significant affect on the amount of amylase in all three experiments but affected amylase activity only in the 24 h experiment. Generally, glucose decreased amylase expression while maltose or cAMP + glucose increased it. Length of feeding period and tissue type also had significant effects on amylase expression. PMID- 24214608 TI - Size and hematological impact of the splenic erythrocyte reservoir in rainbow trout,Oncorhynchus mykiss. AB - Fish were sampled individually, at rest, following air exposures of up to 8 min, during recovery from a 5 min air exposure or after a 5 minute chase. The spleen was photographedin vivo at rest and following 5 min air exposure in one fish. The effect of individual versus serial sampling from the same tank and of MS222 anaesthesia was also examined. Spleen hemoglobin content (SpHb), spleen somatic index (100 * spleen weight/body weight; SSI), blood hemoglobin concentration (Hb), and hematocrit (Ht), were measured. Mean cell hemoglobin concentration (MCHC), erythrocyte reservoir size, and relative contributions of reservoir release, erythrocyte swelling, and plasma water loss to hemoconcentration were calculated. The splenic reservoir contained 0.54 g Hb/kg body (21% of total body Hb), most of which it released between 1 and 3 minutes after the onset of air exposure. The spleen released more than 95% of the erythrocytes it contained at rest within 8 min. The release accounted for 31% of the 5.65 g/dl rise in Hb and 23% of the 26.6% observed increase in Ht after 8 minutes of air exposure. The balance of the increase was caused by erythrocyte swelling and fluid shifts reducing plasma volume. Animals exercised for 5 min showed changes similar to those in fish air exposed for 5 min. Recovery of all parameters was complete in 3 to 6 h, with the exception of MCHC which recovered in 30 min. Serial sampling produced a decrease in SpHb, and R1Wt and induced a significant hemoconcentration. MS222 did not cause erythrocyte release, but failed to prevent it after handling. Many previous reports of Ht and Hb in resting fish are probably high because they were taken under conditions that would cause the spleen to release its contents. PMID- 24214609 TI - Changes in gonadal hormones during oocyte development in the striped bass,Morone saxatilis. AB - Wild striped bass,Morone saxatilis, were collected from coastal waters and spawning areas to describe the endocrine correlates of oocyte development in non captive, migratory fish. The fish were classified according to their most advanced oocytes. Serum levels of estradiol (E2), testosterone (T) and 17alpha 20beta-dihydroxyprogesterone (DHP) were measured by radioimmunoassay (RIA). Females in the primary growth phase and early secondary growth phase (pre vitellogenic) had low levels of plasma steroids, ovarian lipid content and gonadosomatic indices (GSIs). Significant increases in E2, T, ovarian lipid content and GSIs occurred during the vitellogenic phase. Maximum levels of all reproductive parameters were found in prespawning fish sampled in the Hudson River. Mean levels of E2, T, ovarian lipids and GSIs for these fish were 2.0+/ 0.5 ng/ml, 3.0+/-0.3 ng/ml, 24+/-1 mg/g, and 5.6+/-0.3% (mean+/-SEM), respectively. In fish induced to spawn with human chorionic gonadotropin (HCG), DHP levels (1.9+/-0.4 ng/ml) were significantly elevated. Similar levels were found in two fish captured during the spawning season, suggesting that DHP may serve as the maturation-inducing steroid in this species. PMID- 24214610 TI - Osmoregulation in the mudskipper,Boleophthalmus boddaerti I. Responses of branchial cation activated and anion stimulated adenosine triphosphatases to changes in salinity. AB - The mudskipperB. boddaerti, was able to survive in waters of intermediate salinities (4-270/00). Fish submerged in dechlorinated tap water suffered 60% mortality by the fifth day while 60% of those in 100% sea-water (sw) died after the third day of exposure. After being submerged in 50% or 80% sw for 7 days, the plasma osmolality, plasma Na(+) and Cl(-) concentrations and the branchial Na(+) and K(+) activated adenosine triphosphatase (Na(+),K(+)-ATPase) activity were significantly higher than those of fish submerged in 10% sw for the same period. However, the activities of the branchial HCO3 (-) and Cl(-) stimulated adenosine triphosphatase (HCO3 (-),Cl(-)-ATPase) and carbonic anhydrase of the latter fish were significantly greater than those of the former. Such correlation suggests that Na(+),K(+)-ATPase is important for hyperosmotic adaptation in this fish while HCO3 (-)-Cl(-)-ATPase and carbonic anhydrase may be involved in hypoosmotic survival. PMID- 24214611 TI - Osmoregulation in the mudskipper,Boleophthalmus boddaerti II. transepithelial potential and hormonal control. AB - Boleophthalmus boddaerti submerged in 10%, 50% and 80% seawater (sw) for 7 days, had whole body transepithelial potentials (TEP) of 3.3, 18.3 and 22.9 mV, respectively. Hypophysectomy significantly decreased the TEP ofB. boddaerti and reversed the polarity of the TEP of the fish exposed to 10% sw.Hypophysectomy also significantly decreased the branchial Na(+)-K(+) activated adenosine triphosphatase (Na(+),K(+)-ATPase) activity but increased the activity of branchial HCO3 (-)-Cl(-) stimulated adenosine triphosphatase (HCO3 (-),Cl(-) ATPase) inB. boddaerti exposed to 10% sw. However, survival in 10% sw was not significantly impaired by hypophysectomy and no significant change in plasma osmolality and plasma Na(+) and Cl(-) concentrations was observed.Various doses of ovine-prolactin or salmon-prolactin were unable to restore the TEP of hypophysectomizedB. boddaerti in 10% sw to that of the sham-operated fish. However, cortisol increased TEP to a positive value in hypophysectomizedB. boddaerti, though it was still lower than the sham-operated control. Cortisol treatment also affected the plasma osmolality, plasma Na(+) and Cl(-) contents and branchial Na(+),K(+)-ATPase and HCO3 (-),Cl(-)-ATPase activities. Overall, the hormonal control of osmoregulation inB. boddaerti appeared to differ from that of other teleosts. PMID- 24214612 TI - Effects of vasoactive intestinal polypeptide, substance P, 5-hydroxytryptamine, met-enkephalin and neurotensin on the swimbladder smooth muscle of two teleost species,Gadus morhua andAnguilla anguilla. AB - The effects of vasoactive intestinal polypeptide (VIP), substance P (SP), 5 hydroxytryptamine (5-HT), neurotensin (NT) and met-enkephalin (mEnk) on the smooth muscles of the teleost swimbladder were studied in two teleost species, the Atlantic cod (Gadus morhua) and the eel (Anguilla anguilla). The study was made on isolated strip preparations of the muscularis mucosae, using putative transmitters corresponding to the immunoreactive materials that have previously been localized by immunohistochemical methods in nerves or endocrine/paracrine cells of the teleost swimbladder and/or the gastrointestinal canal. VIP was relaxatory on both cod and eel swimbladder smooth muscle, SP and 5-HT were constrictory in both species, and mEnk was excitatory on the eel swimbladder smooth muscle. Clear effects of these agents were usually seen at a concentration ofca. 10 nM in cumulative concentration/effect experiments. NT had no effect in either species. In the eel, the effects on the pneumatic duct were generally greater than on the swimbladder proper. The study indicates that the 5-HT and peptides previously observed by immunohistochemistry have physiological functions in the swimbladder. PMID- 24214613 TI - Actions of epinephrine on the contractility of fast and slow skeletal muscle fibres in teleosts. AB - Fast and slow muscle fibers were isolated from the myotomes of atlantic cod (Gadus morhua L.) and sculpin (Myoxocephalus scorpius L.). Epinephrine was found to have no effect on twitch or sub-tetanic contractions in fast muscle fibres. Isoprenaline (10(-6)M) had no effect on the contractility of slow muscle fibres. In contrast, epinephrine elicited a dose-dependent decrease in the half-time for twitch relaxation (t1/2r), and in most cases a decrease in twitch amplitude. The maximum decrease in t1/2r was around 5-20% of control values (at 10(-6)M epinephrine), with a half maximal response at about 30 nmol l(-1). Responses to epinephrine were unaffected by propranolol and reversed by phentolamine, consistent with the stimulation of alpha-adrenoreceptors. 10(-6)M epinephrine produced a rise in cAMP levels from 1.8 to 3.1 pmol mg dry wt(-1) in cod slow fibres. However, the cellular mechanism underlying the action of epinephrine is unclear since forskolin, a potent activator of adenylate cyclase activity, where it has been investigated, was found to increase not decrease twitch duration and amplitude. The responses of fast and slow fibres to epinephrine and its antagonists were similar in summer (13 degrees C) and winter acclimatized (5-6 degrees C) sculpin.It is suggested that epinephrine may act to modulate the active state of slow muscle fibres at high cruising speeds and thereby increase swimming performance. PMID- 24214614 TI - The use of T cells in hazard characterization of chemical and drug allergens and integration in testing strategies. Foreword. PMID- 24214615 TI - Activation of the TCR complex by peptide-MHC and superantigens. AB - Drug hypersensitivity reactions are immune mediated, with T lymphocytes being stimulated by the drugs via their T-cell antigen receptor (TCR). In the nonpathogenic state, the TCR is activated by foreign peptides presented by major histocompatibility complex molecules (pMHC). Foreign pMHC binds with sufficient affinity to TCRalphabeta and thereby elicits phosphorylation of the cytoplasmic tails of the TCRalphabeta-associated CD3 subunits. The process is called TCR triggering. In this review, we discuss the current models of TCR triggering and which drug properties are crucial for TCR stimulation. The underlying molecular mechanisms mostly include pMHC-induced exposure of the CD3 cytoplasmic tails or alterations of the kinase-phosphatase equilibrium in the vicinity of CD3. In this review, we also discuss triggering of the TCR by small chemical compounds in context of these general mechanisms. PMID- 24214616 TI - Activation of the TCR complex by small chemical compounds. AB - Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal-next to the TCR-that naive T cells require to become activated is generated in the drug hypersensitivity reactions. PMID- 24214617 TI - T cell responses to contact allergens. AB - T lymphocytes are instrumental in the prevention of infections. With their antigen-specific T cell receptor (TCR), these cells recognize short peptides in the peptide-binding groove on MHC molecules of antigen-presenting cells. However, conventional T cells can also recognize non-peptide antigens including carbohydrates, phosphate groups, organic chemicals, and metal ions. The molecular basis of the interaction of TCR with these structures in the context of MHC has been partly solved. Organic chemicals and carbohydrates are recognized when bound to MHC-associated peptides, whereas metal ions are recognized due to their ability to form non-covalent coordination bonds with MHC molecules, bound peptides, and TCR. Peptide-independent metal ion recognition has also been described. PMID- 24214618 TI - Contact hypersensitivity: quantitative aspects, susceptibility and risk factors. AB - The development of allergic sensitisation by environmental chemicals results in allergic contact dermatitis and highly undesirable morbidity and disability. This form of hypersensitivity is mediated by specific T lymphocytes that recognise the chemical sensitiser bound to self-proteins. Use of deliberate experimental contact sensitisation with dinitrochlorobenzene (DNCB) has been used to investigate the human immune system which exhibits dose-related responses. Many factors contribute to whether sensitisation occurs and the nature and magnitude of the immune response. Chemicals vary in sensitising potency, mainly reflecting their intrinsic protein-binding properties. The amount of sensitiser reaching the immune system is determined by many factors of which the concentration (dose per unit area), the relative lipid solubility and molecular weight are the most critical. Host-related factors contributing to the nature and magnitude of immune responses are mainly genetically determined including gender, age, the biochemical/physical integrity of the epidermal barrier and the quality of the innate and adaptive immune systems. The underlying mechanisms must be elucidated before it will be possible to make reliable predictions of whether a given individual will develop allergic sensitisation by a given chemical. PMID- 24214619 TI - Tools and methods for identification and analysis of rare antigen-specific T lymphocytes. AB - T lymphocytes are essential as effector and memory cells for immune defense against infections and as regulatory T cells in the establishment and maintenance of immune tolerance. However, they are also involved in immune pathology being effectors in autoimmune and allergic diseases or suppressors of immunity in cancer, and they often cause problems in transplantation. Therefore, strategies are being developed that allow the in vivo amplification or isolation, in vitro expansion and genetic manipulation of beneficial T cells for adoptive cell therapies or for the tolerization, or elimination of pathogenic T cells. The major goal is to make use of the exquisite antigen specificity of T cells to develop targeted strategies and to develop techniques that allow for the identification and depletion or enrichment of very often rare antigen-specific naive as well as effector and memory T cells. Such techniques are very useful for immune monitoring of T cell responses in diagnostics and vaccination and for the development of T cell-based assays for the replacement of animal testing in immunotoxicology to identify contact allergens and drugs that cause adverse reactions. PMID- 24214620 TI - Human T cell priming assay: depletion of peripheral blood lymphocytes in CD25(+) cells improves the in vitro detection of weak allergen-specific T cells. AB - To develop an in vitro assay that recapitulates the key event of allergic contact dermatitis (ACD), that is the priming of effector T cells by hapten-presenting dendritic cells, and then allows for the sensitive detection of chemical allergens represents a major challenge. Classical human T cell priming assays (hTCPA) that have been developed in the past, using hapten-loaded monocyte derived dendritic cells (MDDCs) as antigen-presenting cells and peripheral blood lymphocytes (PBLs) as responding cells, were not efficient to prime T cells to common allergens with moderate/weak sensitizing properties. Recent progress in the understanding of the effector and regulatory mechanisms of ACD have shown that T cell priming requires efficient uptake of allergens by immunogenic DCs and that it is controlled by several subsets of regulatory cells including CD25(+) Tregs. We therefore analyzed various parameters involved in allergen-specific T cell activation in vitro and showed that priming of allergen-specific T cells is hampered by several subsets of immune cells comprising CD1a(neg) DCs, CD25(+) T cells, and CD56(+) regulatory cells.CD4(+)CD25(+)FoxP3(+) Tregs prevented the in vitro T cell priming to moderate/weak allergens, and depletion of human PBLs in CD25(+) cells significantly increased specific T cell proliferation and IFN-gamma secretion. CD56(+) cells exerted an additional control of T cell priming since co depletion of both CD56(+) and CD25(+) cells improved the magnitude of chemical specific T cell activation. Finally, CD1a(low) MDDCs were able to inhibit T cell activation obtained by allergen-pulsed CD1a(high) MDDC. Moreover, we showed that uptake by DC of allergen-encapsulated nanoparticles significantly increased their activation status and their ability to prompt specific T cell activation. Hence, by combining the different strategies, i.e., depletion of CD25(+) and CD56(+) cells, use of CD1a(high) MDDC, and nanoparticle encapsulation of allergens, it was possible to induce T cell priming to most of the moderate/weak allergens, including lipophilic molecules highly insoluble in culture media. Therefore, the present optimized in vitro human T cell priming assay is a valuable method to detect the sensitizing properties of chemical allergens. PMID- 24214621 TI - Correlation of contact sensitizer potency with T cell frequency and TCR repertoire diversity. AB - Allergic contact dermatitis is a T cell-mediated skin disease. Many hundreds of organic chemicals and some metal ions are contact sensitizers. They induce an innate inflammatory immune response in the skin that results in the priming of contact sensitizer-specific T cells by dendritic cells in the draining lymph nodes. The factors that determine the strength of this T cell response and thereby define the potency of a contact sensitizer are largely unknown. This chapter highlights different variables such as precursor frequency of antigen specific T cells, possible bystander activation, and T cell receptor diversity or avidity of the TCR/peptide-MHC interactions, which might impact the quality and strength of T cell responses to contact sensitizers. In addition, different methods available to determine both the frequency of antigen-specific T cells and T cell receptor repertoires are discussed. Identification of the factors determining potency may allow for the development of suitable in vitro assays for potency assessment of contact sensitizers. PMID- 24214622 TI - On the role of co-inhibitory molecules in dendritic cell: T helper cell coculture assays aimed to detect chemical-induced contact allergy. AB - T cells play a pivotal role in sensitization and elicitation of type IV allergic reactions. While T helper cells sustain and maintain the differentiation of further effector cells, regulatory T cells are involved in control of cytokine release and proliferation, and T killer cells execute cellular lysis, thereby leading to certain levels of tissue damage. According to their central role, the widely applied and OECD-supported test method for the assessment of the sensitization potential of a chemical, i.e., the local lymph node assay (LLNA), relies on the detection of the immune-responsive proliferation of lymphocytes. However, most sensitization assays recently developed take advantage of the initiators of sensitization, dendritic cells (DCs) or DC-like cell lines. Here, we focus on inhibitory molecules expressed on the surface of DCs and their corresponding receptors on T cells. We summarize insight into the function of CTLA-4, the ligands of inducible co-stimulators (ICOSs), and on the inhibitory receptor programmed death (PD). The targeting of immune cell surface receptors by inhibitory molecules holds some promise with regard to the development of T cell based sensitization assays. Firstly, a broader and more sensitive dynamic range of detection could be achieved by blocking inhibitors or by removing inhibiting regulatory T cells from the assays. Secondly, the actual expression levels of inhibitory molecules could be also a valuable indicator for the process of sensitization. Finally, inhibitory molecules in coculture test systems are supposed to have a major influence on DCs by reverse signaling, thereby affecting their differentiation and maturation status in a feedback loop. In conclusion, inhibitory ligands of DC surface receptors and/or their cognate receptors on T cells could serve as useful tools in cell-based assays, directly influencing toxicological endpoints such as sensitization. PMID- 24214623 TI - T cell responses to drugs and drug metabolites. AB - Understanding the chemical mechanisms by which drugs and drug metabolites interact with cells of the immune system is pivotal to our knowledge of drug hypersensitivity as a whole.In this chapter, we will discuss the currently accepted mechanisms where there is scientific and clinical evidence to support the ways in which drugs and their metabolites interact with T cells. We will also discuss bioanalytical platforms, such as mass spectrometry, and in vitro test assays such as the lymphocyte transformation test that can be used to study drug hypersensitivity; the combination of such techniques can be used to relate the chemistry of drug antigen formation to immune function. Ab initio T cell priming assays are also discussed with respect to predicting the potential of a drug to cause hypersensitivity reactions in humans in relation to the chemistry of the drug and its ability to form haptens, antigens and immunogens in patients. PMID- 24214624 TI - Hypersensitivity reactions to beta-lactams. AB - Beta-lactam antibiotics (BLs) are the most frequent cause of hypersensitivity reactions mediated by specific immunological mechanisms, with two main types, IgE reactions or T-cell-dependent responses. From a practical point of view, these reactions can be classified into immediate, for those appearing within 1 h after drug intake, and non-immediate, for those appearing at least 1 h after and usually within 24 h of BL administration. The clinical symptoms differ according to this classification. Urticaria and anaphylaxis are the most frequently recorded symptoms in immediate reactions and maculopapular exanthema and delayed urticaria in non-immediate reactions. Although the exact diagnostic approach differs depending on the underlying mechanism, it is based on the performance of skin testing, laboratory tests, and drug provocation tests.T cells are a key factor in all types of hypersensitivity reactions to BLs, regulating both IgE production or acting as effector cells, with a different profile of cytokine production. A Th1 pattern is observed in both CD4(+) and CD8(+) peripheral T cells in non-immediate reactions, whereas a Th2 pattern is expressed in CD4(+) T cells in immediate reactions. PMID- 24214625 TI - Men in the demographic transition. AB - Women's fertility is the focus of most demographic analyses, for in most mammals, and in many preindustrial societies, variance in male fertility, while an interesting biological phenomenon, is irrelevant. Yet in monogamous societies, the reproductive ecology of men, as well as that of women, is important is creating reproductive patterns. In nineteenth-century Sweden, the focus of this study, male reproductive ecology responded to resource conditions: richer men had more children than poorer men. Men's fertility also interacted with local and historical factors in complex ways to have significant impact on population growth. As a result, "the" demographic transition was local, and locally reversible, in Sweden. Results cannot be simply translated from nineteenth century studies to current attempts to promote fertility decline, because today, male and female resource-fertility curves differ in shape, not only in magnitude. When we translate studies of fertility decline, it is important to study individual fertility and to discern whether, in any particular case, male and female patterns are similar. PMID- 24214626 TI - Mate choice in modern societies : Testing evolutionary hypotheses with behavioral data. AB - Most research on mate choice in modern societies is based on data that may or may not reflect actual mating behavior (e.g., stated preferences, personal advertisements). In the present study, real-life matings were reported by a large representative sample of men and women (N = 1,133). These data were used to test an evolutionary model in which mate choice is hypothesized to depend on resources potentially contributed to reproduction by each sex. Consistent with the model, it was found that (a) men (but not women) of higher social status acquire more mating partners, suggesting that male status is an important criterion in female choice; (b) women's (but not men's) number of partners decreases linearly with age, suggesting that female reproductive potential is an important criterion in male choice; and (c) women (but not men) display a significant relationship between marital dissolution and promiscuity, suggesting that female sexual exclusivity is an important criterion in male choice. These results are discussed in relation to understanding mate choice mechanisms from behavioral data. PMID- 24214627 TI - A sensitive period for learning about food. AB - It is proposed here that there is a sensitive period in the first two to three years of life during which humans acquire a basic knowledge of what foods are safe to eat. In support of this, it is shown that willingness to eat a wide variety of foods is greatest between the ages of one and two years, and then declines to low levels by age four. These data also show that children who are introduced to solids unusually late have a narrower diet breadth throughout childhood, perhaps because the duration of the sensitive period has been shortened. By reducing the costs associated with learning, a sensitive period for food learning should be adaptive for any omnivore (including early humans) that remains in the same environment throughout its life. PMID- 24214628 TI - Psychosocial stress and infertility : Cause or effect? AB - Experimental, theoretical, psychological, and economic barriers have caused physicians to rely on biomedical treatments for infertility at the exclusion of more environmentally oriented ones (e.g., psychosocial stress therapy). An evolutionary model is described for the origin of reproductive failure, suggesting why mammals evolved to be reproductively responsive to the environment and why psychosocial stress should have an especially strong impact on fertility problems. A study of the causal role of psychosocial stress in infertility is then summarized. The paper concludes with implications for future directions for the treatment of infertility and related human reproductive problems. PMID- 24214629 TI - Editorial. PMID- 24214630 TI - Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population. AB - JC and BK polyomaviruses (JCV and BKV) infect humans and can cause severe illnesses in immunocompromised patients. Merkel cell polyomavirus (MCPyV) can be found in skin carcinomas. In this study, we assessed the occurrence of serum antibodies against MCPyV, BKV, and JCV polyomaviruses in a healthy population of the Czech Republic. Serum samples from 991 healthy individuals (age range: 6-64 years) were examined by enzyme-linked immunoassay (ELISA) using virus-like particles (VLPs) based on the major VP1 capsid proteins of these viruses. Overall, serum antibodies against MCPyV, JCV, and BKV were found in 63%, 57%, and 69%, respectively, of this population. For all three viruses, these rates were associated with age; the occurrence of antibodies against MCPyV and JCV was highest for those older than 59 years, while the occurrence of antibodies against BKV was highest in those aged 10-19 years and 20-29 years. This is the first large study to determine the seroprevalence rates for BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population. PMID- 24214632 TI - Processing demands during mental operations. AB - Man possesses a central system of limited capacity. Theorists at first described this system as a single limited capacity channel Two current theoretical alternatives to single-channel theory are (1) the undifferentiated capacity hypothesis that man possesses a pool of capacity units so that interference occurs oniy if the total number of capacity units that mental operations demand exceeds the system limit and (2) the hypothesis that some, but not all, mental operations require space in a limited capacity central mechanism and that any operation that requires space will interfere with any other operation that also demands space. Time on task fails as a sensitive measure of capacity demands because some task components require time but not full processing capacity. The secondary task technique uses the interference between a primary task and a secondary task to assess the extent to which the primary task makes processing demands on the central limited system. Processing demands have been measured for five categories of mental operation: (1) encoding, (2) multiple input, (3) rehearsal, (4) transformation, and (5) responding. PMID- 24214631 TI - FoxP3 provides competitive fitness to CD4+CD25+ T cells in leprosy patients via transcriptional regulation. AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae. FoxP3 have been shown to have important implications in various diseases. The present study describes the mechanism of action of FoxP3 in CD4+CD25+ T cells derived from leprosy patients. Increased molecular interactions of FoxP3 with histone deacetylases 7/9 in the nucleus of CD4+CD25+ T cells derived from borderline lepromatous leprosy/lepromatous leprosy (BL/LL) patients were found to be responsible for FoxP3-driven immune suppression activities during the progression of leprosy. Further, downregulation of CTLA-4 and CD25 genes in siFoxP3-treated PBMCs derived from BL/LL patients elucidated the transcription-activating nature of FoxP3. This observation was supported by direct binding of FoxP3 to the promoter region of the CTLA-4 and CD25 genes, and FoxP3's molecular interaction with histone acetyl transferases. The study also revealed that the increased expression of miR155 in CD4+CD25+ cells from BL/LL governs the competitive fitness of these cells. Again, reduced Annexin V & propidium iodide staining and Nur77 expression, and concomitantly increased Ki-67 positivity suggested that CD4+CD25+ cells derived from BL/LL patients are more competitively fit than those from borderline tuberculoid leprosy/tuberculoid leprosy and healthy controls. Taken together, the study shows the orchestration of FoxP3 leading to competitive fitness of Treg cells in leprosy. PMID- 24214633 TI - Differcntial feature analysis in the recognition memory of reflective and impulsive children. AB - Seventy-two children. 18 reflective, and 18 impulsive first and fifth graders were tested in a forced-choice recognition memory task. Experimental conditions systematically varied the possibility that correct responses could be made on the basis of verbal labels, visual feature analyses, or both. Although reflective children made more correct recognition choices than did impulsive children under all experimental conditions, this difference was, as predicted, significant only in a condition in which the sole basis for correct response depended on a purely visual feature analysis. Order of condition difficulty indicated that visual feature analysis independent of verbal processes was responsible for successful recognition performance in these Ss. Results were discussed with reference to the feature-testing model for recognition proposed by Selfridge and Neisser. PMID- 24214634 TI - Social comparison, attraction, and choice of a comparison other. AB - The effects of attitudinal similarity and task-relevant affiliative status, together with three situational factors (presence or absence of a monetary reward, choice of information source or work partner, and choice made before or after Ss completed preliminary work on the task), on the choice of comparison others were examined. The most significant determinant of the comparison other chosen was attitude similarity (p < .01). There was also a significant interaction between attitude similarity, task-relevant affifliative status, and time of choice (p < .05). The nature of the interaction suggested that general impressions such as conveyed by general attitudinal information may be more important in the selection of referent others than comparability on situation specific factors. PMID- 24214635 TI - Stimulus encoding selectivity at high degrees of paired-associate learning. AB - Sixty-two Ss learned six CCC trigram-digit pairs by the study-test method; 21 Ss continued the PA acquisition trials to a learning criterion of one errorless trial, while 41 Ss were carded to 300% overlearning or 24 trials, whichever came first. The Ss were then shown individual letters of the trigrams, with position cues provided, and were tested for their ability to provide the digit and produce the additional letters. Digit recall was much better to initial letters than to those in the second or third positions of the trigrams; with oveflearning, digit recall improved to the initial letters but not to letters in second and third positions. Production of additional letters of the trigrams was not appreciably related to either cue position or degree of PA learning. There was some evidence ofincreased selectivity with higher degrees of PA learning. PMID- 24214636 TI - Spacing effects in picture memory. AB - Three experiments were conducted to capitalize on the conclusion of Shaffer and Shiffrin (1972) that complex visual scenes are not rehearsed in testing the hypothesis that the effect of spacing on memory is due to rehearsal. In Experiment I, a list of vacation slides was presented in which both the number of repetitions and the spacing of repetitions were varied. Subsequent frequency judgments showed an effect of spacing much like that found using verbal materials. In Experiments II and III, effects of filled and unfilled spacing intervals were compared, and it was concluded that the spacing effect is primarily a function of the duration of the spacing interval. No evidence was found to support the notion that pictures are rehearsed. Rehearsal apparently cannot play the key role in an adequate, completely general explanation of the spacing effect. PMID- 24214637 TI - Prior induced affect and sex differences in attraction. AB - Male (N = 90) and female(N = 90) Ss were shown either 12 humorous or 12 serious TV commercials and were asked to rate each commercial on six 7-point personal feelings scales as well as on a 6-point evaluative (like-dislike) scale. The Ss were then shown the purported evaluative responses of a same-sex stranger which were .17, .50, or .83 similar to their own. Analysis of the personal feelings scales indicated expected differences (p < .001) in affect associated with the two sets of commercials. Females who viewed the serious commercials evidenced greater attraction toward the stranger than did females who saw the humorous commercials (p < .05). The similarity attraction function for males in the humorous condition had a greater slope and a lower y intercept than the similarity attraction function for males in the serious condition. A factor analysis of female affective responses to five socially relevant commercials in the serious set suggested the operation of two affective dimensions, one of which appeared to reflect feelings of social concern. PMID- 24214638 TI - Presentation modality and proactive interference in short-term retention using a mixed-morality distractor task. AB - Two experiments investigated the release from PI following a shift in mode of presentation of the study words. In each experiment, the interpolated task required processing of both auditory (A) and visual (V) information. The results were the same with mixed lists (Experiment I) and with independent groups (Experiment II): A release from PI was obtained following an A to V shift but not following a V to A shift. It was concluded that the mixed-modality filler task has functional characteristics very similar to those of an A filler and that the filler task influences the memory code for study items. PMID- 24214639 TI - Effects of short-term memory contents on short-and long-term memory searches. AB - The Ss memorized a long-term set (LT set) of 20 words before participating in a recognition memory test. On each trial Ss were given a new short-term set (ST set) of from one to four words or one to four digits. The Ss gave a positive response to a test item that was a member of either the ST or the LT set and gave a negative response to a test item not in either set; both words and digits were used as test stimuli. The results indicated that reaction time (RT) to positive test items from the ST set was an increasing function 0f the size of the ST set; the same was also true for negative responses to test digits when the ST set was composed of digits. RT to other test stimuli, however, did not depend on ST set size. These results are consistent with the view that Ss access long-term memory (LTM) and short-term memory (STM) simultaneously rather than sequentially. The results also showed that Ss responded more quickly to test items from the LT set when the ST set contained digits than when it contained words. Negative test items that were words, however, were rejected more slowly when the ST set contained digits than when it contained words. These results suggest that the search of LTM was affected by the contents of STM. PMID- 24214640 TI - An analysis of the visual component in recognition memory for verbal stimuli. AB - Forty Ss were given a continuous recognition memory test in which each word was presented twice, either in the same print or in different print on the two occasions. The results showed that (a) recognition performance was facilitated to a small but statistically significant extent in the same-print condition and that (b) Ss could reliably report first presentation print for recognized items for at least 1(1/2) rain. In a second experiment, the stimuli used were nonsense strings of. from five to seven letters instead of words. This manipulation increased the same-print advantage in recognition but reduced Ss' ability to report first print form. The results indicate that information about the physical features of verbal stimuli is retained in a visual code that is partially' or wholly independent of the verbal code for the same stimuli. The results are inconsistent with the conclusion that the visual code is stored only as a dependent attribute of the verbal code in memory. PMID- 24214641 TI - Sequence redundancy, rating dimensions, and the exposure effect. AB - Two experiments investigated Zajone's (1968) hypothesis that mere repeated exposure to stimuli is a sufficient condition to enhance individuals' attitudes toward those stimuli. In the first experiment, no significant differences in preference were obtained following exposure to high- and low-redundancy sequences of nonsense syllables. In the second study, the effects of repeated exposure were measured along several rating dimensions, revealing significant differences between dimensions. These results were discussed in terms of the limiting conditions of the exposure effect. PMID- 24214642 TI - The perception of identity in simultaneously presented complex visual displays. AB - Two experiments were conducted in order to examine the information processing in a visual matching task, using digit sequences of varying complexity as the stimuli. Traditionally, reaction times for "same" judgments do not fit into a single-process self-terminating feature testing model, while those for "different" judgments do. Bamber (1969) proposed a two-stage model to account for the data, and the results of these experiments support this type of model. Strong evidence implying that Bamber's "identity reporter" has a limited capacity in terms of stimulus complexity was also found. This complexity seems to be deemed by stimulus discriminability and the number of "chunks" of information rather than by "bits" of information being transmitted (Miller, 1956). PMID- 24214643 TI - Memory for redundant information. AB - Ss learned a paragraph consisting of two four-term linear orderings. Such an ordering is comprised of six pairwise relations, three of which (the adjacent pairs) are essential to the establishment of the ordering and three of which (the remote pairs) are redundant. For one of the orderings only the three Adjacent pairs were presented, for the other all six pairs were presented. Previous work indicated that, when Ss are asked to determine whether a test sentence is true (consistent with the ordering) or false (inconsistent with the ordering), proportion correct is higher on the remote pairs than on the adjacent pairs. The present experiment examined Ss' ability to determine whether a particular test sentence had actually been presented. For false sentences the above effect was replicated; for true sentences the effect was reversed. This result supports the argument that Ss store "semantic descriptions" rather than individual sentences. PMID- 24214644 TI - Passage organization and imposed learning strategies in comprehension and recall of connected discourse. AB - Ninety-nine Ss were assigned randomly to learn a passage comprised of six paragraphs in which the statements were organized by concept name, or concept attribute, or in which the statements were scrambled. Each complete passage contained the same 36 statements. These treatments were orthogonally crossed with instructions to employ a name clustering strategy, an attribute clustering strategy, or a subjectively determined organizing strategy. Three learning trials were administered, each of which was followed by free recall. Passages organized by concept name were found to result in greater recall than passages organized by attributes. The name clustering strategy was more dominant than the attribute clustering strategy, lncongruence between passage organization and advocated clustering strategy resulted in greater recall than did congruency. Implications of these results for cognitive processing of information are discussed. PMID- 24214645 TI - Can characters be classified directly as digits vs letters or must they be identified first? AB - Two experiments were addressed to the question of whether or not Ss can distinguish between letters and digits without identifying the characters. In Experiment I Ss attempted to identify noisy characters; a character was said to be implicitly classified correctly if the identification response, whether correct or incorrect, was in the same category vis-a-vis the letter-digit distinction as the stimulus. Implicit classification of characters for which the identification response was incorrect was very little better than chance. The task in Experiment II was to classify the characters directly. The explicit classification performance in this case was poorer than the implicit classification performance of Experiment I. The results were taken as evidence that Ss could not distinguish between letters and digits unless they could identify the characters. PMID- 24214646 TI - Some characteristics of word encoding. AB - This paper presents the results of a series of experiments using the release from proactive inhibition technique for identifying the salient encoding attributes of words. The technique uses the Brown-Peterson paradigm, but, after three trials on words of one class, a fourth trial is given with words of another class. The power of the class encoding is inferred from the extent of gain (release from PI) found on the shift trial. The studies reported show a high degree of effectiveness for semantic variables; practically no effectiveness for grammatical variables; a moderate amount for physical variables (i.e., figure ground shift); and varying amounts for other shifts such as word frequency, imagery, language of the presentation to bilingual Ss. Some evidence is also given for the occurrence of simultaneous multiple encoding. PMID- 24214647 TI - Higher order encoding: Process or state? AB - While prior data has seemed to suggest that learning occurs as a result of encoding information into higher order memory units, rather than the formation of interitem associations, the process whereby the encoding occurs has been left relatively unspecified. Two encoding models were outlined which differed to the extent that one assumed that encoding occurred as an active process after the specific items of information were registered in memory, while the other assumed that information is initially registered in memory in the encoded state. The results from two studies seem to offer the most support for the second of these two models. PMID- 24214648 TI - Memory codes and negative transfer. AB - A view of transfer phenomena in terms of composite memory codes, code independence, and modification of sampling probability over a stimulus-defined retrieval search space is discussed. PMID- 24214649 TI - Coding of nonsense vs the detection of patterns. AB - Two theories are contrasted: coding information into arbitrary characters vs extracting patterns from a flux of stimulation. It is argued that coding is the process people use to memorize nonsense and, for that reason, is a poor model for the applied psychology of learning. The contrasting idea, that Ss perceive patterns and extract information. can be used to improve education by leading teachers to organize their material. It is also argued that most demonstrations of coding can be interpreted as examples of pattern perception. PMID- 24214650 TI - Experimental analysis of coding processes. AB - The first part of the paper reports an investigation of the effects of the concreteness-imagery (C-I) value of stimuli and responses on the long-term retention of paired-associate lists. With degree of learning equated, the measures of retention after a 1-week interval showed a significant interaction of Stimulus by Response C-I: When the responses had a high value, recall was substantially better with low than with high stimuli; when the responses were low, there was no reliable difference as a function of stimulus value. Recall was best when abstract stimuli were paired with concrete responses. The second part of the paper is addressed to some current issues in the analysis of coding processes. Major emphasis is placed on the experimental and theoretical differentiation of encoding and decoding processes. PMID- 24214651 TI - The concept of coding in learning-memory theory. AB - The concept of coding, which refers to what is stored in memory during learning, is defended, as an important and necessary conceptual advance in learning-memory theory during the last decade. It is maintained that the concept covers a wide variety of functionally different coding operations, with many specifics of its operation still to be experimentally determined, and that attempts to restrict its meaning to arbitrary transformational coding, as suggested by Restle, should be rejected. The paper comments on the empirical contributions to coding theory by Johnson, Wickens, Martin, and Postman and Bums in the symposium for which it served a discussant function. PMID- 24214652 TI - Percutaneous management of late leak after lariat transcatheter ligation of the left atrial appendage in patients with atrial fibrillation at high risk for stroke. AB - Left atrial appendage (LAA) occlusion or ligation is a novel approach to stroke prevention in atrial fibrillation that may obviate the need for long-term anticoagulation. The Lariat device has received Food and Drug Administration 510K clearance for the approximation of soft tissue and has been applied to transcatheter LAA ligation using a combined trans-pericardial and transseptal approach. The occurrence of late leak after transcatheter LAA ligation and its percutaneous management has not been previously reported. Herein, we report three cases of late leak with reconstitution of the LAA after initially successful Lariat closure, and present a simple percutaneous technique for leak closure. PMID- 24214654 TI - Understanding older adults' motivators and barriers to participating in organized programs supporting exercise behaviors. AB - Little is known about older adults' perceptions of organized programs that support exercise behavior. We conducted semi-structured interviews with 39 older adults residing in King County, Washington, who either declined to join, joined and participated, or joined and then quit a physical activity-oriented program. We sought to explore motivators and barriers to physical activity program participation and to elicit suggestions for marketing strategies to optimize participation. Two programs supporting exercise behavior and targeting older persons were the source of study participants: Enhance((r))Fitness and Physical Activity for a Lifetime of Success. We analyzed interview data using standard qualitative methods. We examined variations in themes by category of program participant (joiner, decliner, quitter) as well as by program and by race. Interview participants were mostly females in their early 70s. Approximately half were non-White, and about half had graduated from college. The most frequently cited personal factors motivating program participation were enjoying being with others while exercising and desiring a routine that promoted accountability. The most frequent environmental motivators were marketing materials, encouragement from a trusted person, lack of program fees, and the location of the program. The most common barriers to participation were already getting enough exercise, not being motivated or ready, and having poor health. Marketing messages focused on both personal benefits (feeling better, social opportunity, enjoyability) and desirable program features (tailored to individual needs), and marketing mechanisms ranged from traditional written materials to highly personalized approaches. These results suggest that organized programs tend to appeal to those who are more socially inclined and seek accountability. Certain program features also influence participation. Thoughtful marketing that involves a variety of messages and mechanisms is essential to successful program recruitment and continued attendance. PMID- 24214653 TI - Detection of single photons by toad and mouse rods. AB - Amphibian and mammalian rods can both detect single photons of light even though they differ greatly in physical dimensions, mammalian rods being much smaller in diameter than amphibian rods. To understand the changes in physiology and biochemistry required by such large differences in outer segment geometry, we developed a computational approach, taking into account the spatial organization of the outer segment divided into compartments, together with molecular dynamics simulations of the signaling cascade. We generated simulations of the single photon response together with intrinsic background fluctuations in toad and mouse rods. Combining this computational approach with electrophysiological data from mouse rods, we determined key biochemical parameters. On average around one phosphodiesterase (PDE) molecule is spontaneously active per mouse compartment, similar to the value for toad, which is unexpected due to the much smaller diameter in mouse. A larger number of spontaneously active PDEs decreases dark noise, thereby improving detection of single photons; it also increases cGMP turnover, which accelerates the decay of the light response. These constraints explain the higher PDE density in mammalian compared with amphibian rods that compensates for the much smaller diameter of mammalian disks. We further find that the rate of cGMP hydrolysis by light-activated PDE is diffusion limited, which is not the case for spontaneously activated PDE. As a consequence, in the small outer segment of a mouse rod only a few activated PDEs are sufficient to generate a signal that overcomes noise, which permits a shorter lifetime of activated rhodopsin and greater temporal resolution. PMID- 24214655 TI - Analyses of the folding properties of ferredoxin-like fold proteins by means of a coarse-grained Go model: relationship between the free energy profiles and folding cores. AB - The folding mechanisms of proteins with multi-state transitions, the role of the intermediate states, and the precise mechanism how each transition occurs are significant on-going research issues. In this study, we investigate ferredoxin like fold proteins which have a simple topology and multi-state transitions. We analyze the folding processes by means of a coarse-grained Go model. We are able to reproduce the differences in the folding mechanisms between U1A, which has a high-free-energy intermediate state, and ADA2h and S6, which fold into the native structure through two-state transitions. The folding pathways of U1A, ADA2h, S6, and the S6 circular permutant, S6_p54-55, are reproduced and compared with experimental observations. We show that the ferredoxin-like fold contains two common regions consisting folding cores as predicted in other studies and that U1A produces an intermediate state due to the distinct cooperative folding of each core. However, because one of the cores of S6 loses its cooperativity and the two cores of ADA2h are tightly coupled, these proteins fold into the native structure through a two-state mechanism. PMID- 24214657 TI - Airways obstruction and pulmonary capillary blood volume in children with sickle cell disease. PMID- 24214658 TI - Mesenchymal origin of multipotent human testis-derived stem cells in human testicular cell cultures. AB - In contrast to mouse germ cell-derived pluripotent stem cells, the pluripotent state of human testis-derived embryonic stem cell (ESC)-like that spontaneously arise in primary testicular cell cultures remains controversial. Recent studies have shown that these cells closely resemble multipotent mesenchymal stem cells (MSCs), raising the question of their origin and designating these cell populations as multipotent human testis-derived stem cells (mhtSCs) rather than truly ESC-like cells. Here, we evaluate the origin of mhtSCs in vitro by culturing selected testicular cell types. We demonstrate that mhtSCs can be obtained equally efficiently in cultures of pure testicular somatic cells devoid of germ cells. Conversely, cultures with a purified population of germ cells/spermatogonia do not produce any mhtSCs. Based on common molecular characteristics of the somatic starting population and mhtSCs, we conclude that mhtSCs colonies originate from somatic mesenchymal progenitors present in primary testicular cell cultures and do not arise from germ cells undergoing incomplete reprogramming in vitro. PMID- 24214659 TI - A highly stretchable, fiber-shaped supercapacitor. PMID- 24214656 TI - Attention deficit hyperactivity disorder. AB - Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder's pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID- 24214660 TI - Morphology and function: MR pineal volume and melatonin level in human saliva are correlated. AB - PURPOSE: To investigate the relation between circadian saliva melatonin levels and pineal volume as determined by MRI. Plasma melatonin levels follow a circadian rhythm with a high interindividual variability. MATERIALS AND METHODS: In 103 healthy individuals saliva melatonin levels were determined at four time points within 24 h and MRI was performed once (3.0 Tesla, including three dimensional T2 turbo spin echo [3D-T2-TSE], susceptibility-weighted imaging [SWI]). Pineal volume as well as cyst volume were assessed from multiplanar reconstructed 3D-T2-TSE images. Pineal calcification volume tissue was determined on SWI. To correct for hormonal inactive pineal tissue, cystic and calcified areas were excluded. Sleep quality was assessed with the Landeck Inventory for sleep quality disturbance. RESULTS: Solid and uncalcified pineal volume correlated to melatonin maximum (r = 0.28; P < 0.05) and area under the curve (r = 0.29; P < 0.05). Of interest, solid and uncalcified pineal volume correlated negatively with the sleep rhythm disturbances subscore (r = -0.17; P < 0.05) despite a very homogenous population. CONCLUSION: Uncalcified solid pineal tissue measured by 3D-T2-TSE and SWI is related to human saliva melatonin levels. The analysis of the sleep quality and pineal volume suggests a linkage between better sleep quality and hormonal active pineal tissue. PMID- 24214661 TI - Evaluation and the NIH clinical and translational science awards: a "top ten" list. AB - Since 2006, a total of 61 Clinical and Translational Science Institutes (CTSAs) have been funded by the National Institutes of Health (NIH), with the aim of reducing translation time from a bench discovery to when it impacts patients. This special issue of Evaluation & the Health Professions focuses on evaluation within and across the large, complex system of the CTSA Program of NIH. Through insights gained by reading the articles in this special edition and the experience of the authors, a "top ten" list of lessons learned and insights gained is presented. The list outlines issues that face those who evaluate the influence of the CTSA Program, as they work to anticipate what will be needed for continuing success. Themes include (1) considering the needs of stakeholders, (2) the perspective of the evaluators, (3) the importance of service improvement, (4) the importance of teams and people, (5) costs and return on investments, (6) methodology considerations to evaluate the CTSA enterprise, (7) innovation in evaluation, (8) defining the transformation of research, (9) evaluating the long term impact of the CTSAs on public health, and (10) contributing to science policy formulation and implementation. The establishment of the CTSA Program, with its mandated evaluation component, has not only influenced the infrastructure and nature of translational research but will continue to impact policy and management in science. PMID- 24214662 TI - Heterogeneity at work: implications of the 2012 Clinical Translational Science Award evaluators survey. AB - The Clinical and Translational Science Award (CTSA) program is an ambitious multibillion dollar initiative sponsored by the National Institutes of Health (NIH) organized around the mission of facilitating the improved quality, efficiency, and effectiveness of translational health sciences research across the country. Although the NIH explicitly requires internal evaluation, funded CTSA institutions are given wide latitude to choose the structure and methods for evaluating their local CTSA program. The National Evaluators Survey was developed by a peer-led group of local CTSA evaluators as a voluntary effort to understand emerging differences and commonalities in evaluation teams and techniques across the 61 CTSA institutions funded nationwide. This article presents the results of the 2012 National Evaluators Survey, finding significant heterogeneity in evaluation staffing, organization, and methods across the 58 CTSAs institutions responding. The variety reflected in these findings represents both a liability and strength. A lack of standardization may impair the ability to make use of common metrics, but variation is also a successful evolutionary response to complexity. Additionally, the peer-led approach and simple design demonstrated by the questionnaire itself has value as an example of an evaluation technique with potential for replication in other areas across the CTSA institutions or any large-scale investment where multiple related teams across a wide geographic area are given the latitude to develop specialized approaches to fulfilling a common mission. PMID- 24214663 TI - Bilateral and unilateral stenting for malignant hilar obstruction: a systematic review and meta-analysis. AB - BACKGROUND: Stents are used for palliating inoperable malignant bile duct hilar obstruction. It is not clear if bilateral stenting provides any advantage over unilateral stenting in these patients. Compare bilateral and unilateral stenting in malignant hilar obstruction. STUDY SELECTION CRITERIA: Studies using stents for palliation in patients with malignant hilar obstruction were selected. DATA COLLECTION AND EXTRACTION: Articles were searched in MEDLINE, PubMed, Ovid journals, CINAH, International Pharmaceutical Abstracts, OLDMEDLINE, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Two reviewers independently searched and extracted data. Any differences were resolved by mutual agreement. STATISTICAL METHODS: Pooled proportions were calculated using both the Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). The heterogeneity among studies was tested using Cochran's Q test based upon inverse variance weights. The initial search identified 1,640 reference articles, of which 169 were selected and reviewed. Thirteen studies (n = 340) for bilateral metallic stents, eight studies (n = 575) for unilateral metallic stents, eight studies (n = 367) for bilateral plastic stenting, and seven studies (n = 850) for unilateral plastic stenting which met the inclusion criteria were included in this analysis. Pooled data are shown in Tables 1 and 2. The pooled estimates by the fixed and random effect models were similar. The p for chi-squared heterogeneity for all the pooled accuracy estimates was >0.10. Bilateral metal stenting seems to have lower odds of overall complications when compared to unilateral metallic stenting. Bilateral metal stents seem to have higher odds of lowering bilirubin than unilateral metal stents, but the 30-day mortality was no different. For metal stents, bilateral metal stents are superior in palliating symptoms due to hyperbilirubinemia. Unilateral plastic stenting seems to have similar odds of overall complications, cholangitis, and 30-day mortality when compared to bilateral plastic stenting for malignant hilar strictures. In patients with malignant hilar stricture, unilateral plastic stenting is comparable to bilateral plastic stenting for adverse events. PMID- 24214664 TI - Actual status of clinical diagnosis in patients with primary gallbladder cancer associated with adenomyomatosis. AB - AIM: The purpose of this study was to reveal differences in clinical diagnosis of gallbladder cancer among patients with or without adenomyomatosis (ADM) by analyzing demonstrated tumor patterns on imaging and diagnostic opportunities. METHODS: Ninety-seven patients with gallbladder cancer were enrolled. Demonstrated imaging patterns were classified into mass lesion (ML), wall thickening (WT), and papillary lesion (PL). Clinical status during periodic follow up and other diagnostic opportunities were determined from medical records. RESULTS: All adenomyomatosis-associated cases were diagnosed at the T2 or higher stage. The distribution of demonstrated imaging patterns was significantly different between the adenomyomatosis-associated and non adenomyomatosis-associated groups (p = 0.0002). No adenomyomatosis-associated gallbladder cancer had the PL pattern, which was readily identifiable and characteristic of early-stage cancer. The WT pattern presented difficulties for diagnosis, and the ML pattern was relatively specific, although most of these cases were at advanced stages. Approximately 40% of ADM patients were found to be in advanced stages of gallbladder cancer, in spite of undergoing periodic follow up. CONCLUSIONS: This study revealed the difficulty of early diagnosis of primary gallbladder cancer in the setting of concurrent ADM. Current results suggest the possible utility of preventive cholecystectomy for management of asymptomatic ADM patients. PMID- 24214665 TI - Structure and magnetism of epitaxial PrVO3 films. AB - The interplay between charge, spin, orbital and lattice degrees of freedom in transition metal oxides has motivated extensive research aiming to understand the coupling phenomena in these multifunctional materials. Among them, rare earth vanadates are Mott insulators characterized by spin and orbital orderings strongly influenced by lattice distortions. Using epitaxial strain as a means to tailor the unit cell deformation, we report here on the first thin films of PrVO3 grown on (001)-oriented SrTiO3 substrate by pulsed laser deposition. An extensive structural characterization of the PrVO3 films, combining x-ray diffraction and high-resolution transmission electron microscopy studies, reveals the presence of oriented domains and a unit cell deformation tailored by the growth conditions. We have also investigated the physical properties of the PrVO3 films. We show that, while PrVO3 exhibits an insulating character, magnetic measurements indicate low-temperature hard-ferromagnetic behavior below 80 K. We discuss these properties in view of the thin-film structure. PMID- 24214666 TI - Green synthesis and biological evaluation of new di-alpha-aminophosphonate derivatives as cytotoxic agents. AB - A series of novel di-alpha-aminophosphonate derivatives were synthesized by a one pot method in the presence of PEG-H2 O under ultrasonic irradiation and were characterized by IR, (1) H NMR, (13) C NMR, mass spectrometry, and elemental analysis. The newly synthesized compounds were evaluated for their cytotoxic activities against the human lung cancer cell line H1299 and the human breast cancer cell line MCF7 in vitro by the MTT method. All compounds showed moderate cytotoxic activity on both cell lines, and compounds 4b and 4c showed marked activity. PMID- 24214667 TI - Comparative study of acetylcholine synthesis in organs of freshwater teleosts. AB - The activity of acetylcholine (ACh) synthesizing enzyme, choline acetyltransferase (ChAT), and the content of ACh were determined in the brain, heart, red trunk muscle and midgut of 12 freshwater teleost species belonging to eight families: carp (Cyprinus carpio), tench (Tinca tinca), silver carp (Hypophthalmichtys molitrix), bighead (Hypophthalmichtys nobilis), wels (Silurus glanis), cat fish (Ictalurus nebulosus), eel (Anguilla anguilla), rainbow trout (Oncorhynchus mykiss), pike (Esox lucius), pike-perch (Stizosteidon lucioperca), ruffe (Acerina cernua) and pumpkinseed (Lepomis gibbosus). The rate of ACh degradation in the same tissues was characterized by measuring the activity of acetylcholinesterase (AChE). Comparisons by statistical evaluation of cholinergic parameters in the corresponding organs were made between the species or families. The highest ACh concentration was found in the brain (between 9.6 and 16.0 nmol/g), and the gut (4.6 to 17.4 nmol/g), followed by the heart (1.4 to 3.9 nmol/g) and trunk muscle (1.2 to 3.8 nmol/g). Good correlations were found between the ACh content and the ChAT activity in all the organs studied. The correlation coefficients were 0.92 and 0.72 for the brain and heart, respectively. The activity of ChAT and the amount of ACh found in the brain and trunk muscle varied considerably from one family to another, but was of comparable degree within one family. It was concluded that differences in the cholinergic parameters may reflect different feeding and swimming behavioral patterns. PMID- 24214668 TI - An enkephalin analog stimulates growth of tilapia. AB - A synthetic enkephalin analog (Tyr-D-Trp-Ala-D-Phe-NH2) was administered to juvenile hybrid tilapia (Tilapia nilotica *T. aurea) by immersing the fish for 15 minutes per week into one of two doses of the hormone for 8 weeks. Growth, food conversion efficiency, body weight, specific growth rate, food conversion efficiency and feed consumption were all significantly increased as a result of enkephalin treatment. The low dose (10ug/100 ml water) of enkephalin analog had a better stimulation effect than that of the high dose (100ug/100 ml water). Liver protein and protein/DNA ratio were higher in both treatment groups than in the control group. Tissue-body indices and muscle proximate composition were similar in the treatment and control groups. The growth stimulation in fish treated with the enkephalin analog was possibly mediated by an increase in growth hormone secretion. PMID- 24214669 TI - Changes in plasma glucagon and insulin associated with fasting in sea bass (Dicentrarchus labrax). AB - Juvenile sea bass (Dicentrarchus labrax) were fasted for 22 days and changes in plasma insulin, glucagon and glucose levels, as well as glycogen and protein content in liver and muscle were analyzed. Glucagon increased initially on the 4th day of fasting. The glucagon/insulin ratio (G/I) increased from a value of 0.11+/-0.02 (24h of fasting) to 0.21+/-0.05 (4th day of fasting). Thereafter, both glucagon and insulin levels decreased and remained at low concentrations until the 22nd day of fasting. Plasma glucose levels fell at the beginning of fasting, stabilized between the 4th and 8th day, and gradually declined during the rest of the experiment. There was a body weight loss of 15% and a significant decrease in both the hepatosomatic index and mesenteric fat. The decrease in the percentage of muscle proteins was not significant, while liver glycogen content showed a sharp decline. PMID- 24214670 TI - Intracellular transport of ovalbumin afterin vivo endocytosis in rainbow trout liver. AB - The intracellular handing of a mannose-terminated glycoprotein taken up in rainbow trout liver cells by receptor-mediated endocytosis has been studied. The intracellular transport and degradation of ovalbumin (OA) were studied by means of subcellular fractionation in Nycodenz gradients and by differential centrifugation following intravenous injection of the ligand. By using OA labelled with(125)I-tyramine cellobiose ((125)I-TC), the subcellular distribution of labelled degradation products could be studied, since they are trapped intracellularly in the organelle where the degradation takes place. (125)I-TC-OA was shortly after injection (45 min) localized in a homogenous population of endosomes. Labelled degradation products firs appeared in an organelle with the same density distribution as the endosomes. In livers homogenized 2h after injection the degradation products appeared in organelles with increasing size and density. After 24h, the degradation products were recovered in at least two populations of lysosomes with a distribution profile which coincided with that of the lysosomal enzyme beta-acetylglucosaminidase.The heterogeneous distribution of the late degradation products seemed not to be due to uptake of ligand in different liver cell types as only the parenchymal liver cells took up labelled OA after intravenous injection of the ligand. PMID- 24214671 TI - Demonstration of putative membrane and cytosol steroid receptors for 17alpha, 20beta-dihydroxy-4-pregnen-3-one in brook troutSalvelinus fontinalis oocytes by photoaffinity labelling using synthetic progestin 17,21-dimethyl-19-nor-pregn-4,9 diene-3,20-dione (R5020). AB - Cytosol from brook trout ovarian follicles (stages 1-3) was photoaffinity (PA) labelled using synthetic progestin 17,21-dimethyl-19-nor-pregn-4,9-diene-3,20 dione ([(3)H]R5020). The covalently bound cytosol protein had a relative mass of 501,000 Mr following Sephacryl S-300 column chromatography. The zona radiata membrane fraction from brook trout oocytes which had gone through the first phase of meiotic maturation (stages 6-7) was isolated by ultracentrifugation of the whole oocytes. The zona radiata solubilized protein presumably from the oocyte membrane was also PA labelled and found to give a peak at 355,000 Mr. The SDS PAGE of the cytosol and zona radiata PA labelled protein gave very similar subunits indicating that the membrane protein and the cytosol protein, both of which bind the maturation inducing steroid (MIS) 17alpha,20beta-dihydroxy-4 pregnen-3-one (17alpha,20beta-DHP), have similar subunit structures. The isolated zona radiata protein showed cooperativity of binding to [(3)H]17alpha,20beta-DHP and PA labelling to [(3)H]R5020. The association constant (Ka) was 2.0*10(7)M(-1) and maximum binding capacity (Nmax) 427 fmoles/mg protein with MIS [(3)H]17alpha,20beta-DHP.No evidence for nuclear binding of MIS [(3)H]17alpha,20beta-DHP or PA labelling of [(3)H]R5020 to nuclei was observed. The nuclei were isolated from stages 1 and 3 fresh ovarian follicles of brook trout. The experimental evidence presented demonstrates the presence of MIS 17alpha,20beta-DHP receptor-like protein from the zona radiata membranes by PA labelling in brook trout oocytes during final stages of maturation. PMID- 24214672 TI - Transport of 17alpha,20beta-dihydroxy-4-pregnen-3-one in brook troutSalvelinus fontinalis ovarian follicles. AB - Extremely low levels of the maturation inducing steroid (MIS) 17alpha,20beta dihydroxy-4-pregnen-3-one (17alpha,20beta-DHP) were found in the ooplasm and ovarian follicle membranes of Atlantic salmonSalmo salar ouananiche, a finding that is at variance with the elevated blood levels of the steroid. The uptake of MIS at physiological concentrations into brook trout follicles occurred by passive diffusion. Uptake of the steroid into the ovarian follicle membrane, consisting of zona radiata and the attached follicle cells, deviated from linearity in a double reciprocal plot. These results suggest that 17alpha,20beta DHP is binding to a receptor-like protein in the ovarian follicle or the zona radiata membrane surrounding the oocyte, and extend our previous demonstration of 17alpha,20beta-DHP receptor-like activity in the zona radiata membrane of the late stage brook trout oocytes. An oocyte cytoplasmic receptor gave subunits on SDS PAGE that were similar to the membrane and cytosol receptors previously described. PMID- 24214673 TI - Dosage-dependent differences in the effect of aromatizable and nonaromatizable androgens on the resulting phenotype of coho salmon (Oncorhynchus kisutch). AB - This study was conducted to investigate whether aromatization to estrogen could be the cause for the paradoxical feminization of gonads of sexually undifferentiated fish after treatment with androgen at either high doses or for long periods. The aromatizable androgen 17alpha-methyltestosterone (MT) and the nonaromatizable androgen 17alpha-methyldihydrotestosterone (MDHT) were administered to groups of newly hatched coho salmon (Oncorhynchus kisutch) in a single 2h immersion at concentrations ranging from 6.25 to 6,400ug/l. The effects of treatment were evaluated by determining the resultant proportion of males in each experimental group. The effects of steroid administration on the final mean weight, length and condition factor were also determined. An increase in all these three variables was observed in the groups treated with the higher doses of MT. Regarding the resultant sexual phenotype, the response to both androgens was similar at the majority of doses tested. However, at the highest dose, the proportion of females increased with respect to that of males for MT, but not for MDHT. Since the major difference between the two androgens tested is their capacity to be aromatized, it seems that aromatization to estrogen, rather than inhibition of the biosynthesis of endogenous androgen, may explain the paradoxical feminization encountered. PMID- 24214674 TI - Lipids of arctic charr,Salvelinus alpinus (L.) I. Dietary induced changes in lipid class and fatty acid composition. AB - Arctic charr (Salvelinus alpinus L.) were fed either a commercial diet or six experimental test diets containing coconut oil and different polyunsaturated fatty acids (PUFA) at a level of 1% by dry weight. Best growth rates were observed with the commercial diet, worst with diet containing coconut oil with no PUFA. An increase in hepatic lipid, hepatic sterol esters and muscular moisture content, and a decrease in muscular lipid was generally found in fish fed the test diets compared to those maintained on the commercial diet.Phosphatidylcholine was the dominant polar lipid (PL) class in all tissues examined. Extensive modification of dietary saturated fatty acids into 18:1 (n-9) was observed in tissue triacylglycerols (TAG) of fish fed test diets. No changes occurred with the commercial diet.Dietary PUFA were essentially incorporated unchanged into tissue TAG of all fish in the present study. PUFA composition of hepatic phospholipids was significantly influenced by that contained in the diets. However both 18:2 (n-6) and 18:3 (n-3) in the test diets were extensively elongated and desaturated prior to incorporation into PL. The (n-9) PUFA content was always higher in liver of fish fed the test diets. When 18:2 (n-6) and 18:3 (n-3) were supplied together, the level of (n-3) PUFA exceeded those of (n-6) PUFA. Muscle PL were less influenced by diet than liver. In muscle (n-3) PUFA were always the predominant PUFA irrespective of diet. Only low amounts of (n-9) PUFA were found. It is suggested that (n-3) PUFA are the prime essential fatty acids for Arctic charr, and that they are used in preference to (n-6) PUFA for elongation, desaturation and incorporation into PL. The results suggest that the quantitative requirement of Arctic charr for EFA is may be higher than that of other salmonids. PMID- 24214676 TI - On the blood volume of the Mediterranean dogfish,Scyliorhinus canicula. AB - The blood volume of the Mediterranean dogfish,Scyliorhinus canicula was determined to be 4.06+/-0.92 ml/100 g body weight. This result is discussed in relation with the dye dilution technique used, the degree of dye binding with circulating plasma proteins and the values and techniques used by other authors. PMID- 24214675 TI - Magnesium status in freshwater fish, common carp (Cyprinus carpio, L.) and the dietary protein-magnesium interaction. AB - Common carp juveniles were fed for 9 weeks one of the eight semipurified diets containing graded levels of magnesium, 0.08, 0.6, 1.1, 3, 2 g Mg kg(-1) and 25 or 44% protein.Fish growth and feed utilization were significantly affected by both Mg and protein levels in the diets. Significant interaction between these two studied variables existed in relation to the fish performance as well as to mean deposition rate of several minerals in common carp body. The fish fed diets containing 0.08 g Mg kg(-1) had reduced growth and developed deficiency signs such as muscle flaccidity and skin hemorrhages.Results indicated that a minimum Mg level of 0.6 g Mg kg(-1) was required to elevate plasma and bone magnesium content and to reduce the whole body Ca concentration (hypercalcinosis symptom). Further increase of dietary Mg up to 3.2 g Mg kg(-1) improved growth rate of fish insignificantly, but the deposition rate of dietary Mg fell to as low as 7.4 and 10.7 percent in low- and high-protein diet fed fish, respectively. In Mg deficient fish, considerable amount of magnesium was absorbed via extra-oral routes, however, this way of the covering magnesium need becomes insufficient in fast growing fish. PMID- 24214677 TI - The effects of temperature on benzo[a]pyrene metabolism and adduct formation in the gulf toadfish,Opsanus beta. AB - In order to examine the effects of temperature on benzo[a]pyrene (BaP) metabolism and adduct formation in the absence of the effects of temperature on uptake, gulf toadfish,Opsanus beta, were given a dose of 0.05 mg/kg(3)H-BaPvia caudal vein cannulae at their acclimation temperatures. (18 or 28 degrees C) or following an acute temperature change (18 to 28 degrees C or 28 to 18 degrees C). After 72h, BaP-derived radioactivity was detected in all tissues examined and, as in otherin vivo studies of fish, the highest levels were found in the bile, the liver and the kidney. Temperature did not affect the total amount of BaP metabolized and excreted to the bile, but there were significant quantitative differences between temperature treatments in the classes of Phase I metabolites accumulated. Fish acclimated to high temperature accumulated more BaP triols and tetrols (breakdown products of highly carcinogenic BaP diol epoxides) than fish acclimated at low temperature regardless of exposure temperature: the proportion of biliary metabolites as tetrols and triols in each of the four temperature treatments (acclimation: exposure temperature), 28:18, 28:28, 18:18 and 18:28 degrees C were 21.3+/-3.6, 58.1+/-6.1, 14.2+/-1.8 and 20.9+/-3.2% (mean+/-SEM, n=4), respectively. Significant quantities of BaP-DNA and BaP-hemoglobin adducts were detected; however, only the amounts of BaP-DNA adducts showed sensitivity to temperature. As predicted from our metabolite data, high acclimation or exposure temperature led to a significant increase in the amount of BaP-DNA adducts formed: adduct formation in the temperature treatments, 28:18, 28:28, 18:18 and 18:28 degrees C were 342+/-52, 526+/-51, 155+/-42 and 252+/-55 fg BaP/ ug DNA (mean+/-SEM, n=4), respectively. These results are discussed in the context of mechanisms of high temperature-enhancement of carcinogenesis in fish. PMID- 24214678 TI - Exploring extra-cellular proteins in methicillin susceptible and methicillin resistant Staphylococcus aureus by liquid chromatography-tandem mass spectrometry. AB - Staphylococcus aureus (S. aureus) strains cause several diseases in humans from minor skin infections to severe lethal infections. To explore the virulence determinants of this important microorganism, two clinical isolates of methicillin susceptible S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) were subjected to proteomic analysis of their extracellular products using liquid chromatography-tandem mass spectrometry. The numbers of proteins identified in MSSA and MRSA extracellular products were 168 and 261; respectively, from them 117 were shared, while 144 proteins were unique to MRSA. The shared proteins, having a higher protein score with increased number of peptide matches in MRSA over MSSA, reflect the relatively active secretory state of MRSA rather than biased analytical variances. Characteristic determinants for MRSA were identified; mostly found to play a role in the virulence. We conclude that MRSA produces distinct proteins considered as its virulence determinants and we found that the shared extracellular products are more abundant in MRSA than MSSA that supporting the high invasiveness of MRSA over MSSA in pathogenesis. PMID- 24214679 TI - Pyocyanin: production, applications, challenges and new insights. AB - Pseudomonas aeruginosa is an opportunistic, Gram-negative bacterium and is one of the most commercially and biotechnologically valuable microorganisms. Strains of P. aeruginosa secrete a variety of redox-active phenazine compounds, the most well studied being pyocyanin. Pyocyanin is responsible for the blue-green colour characteristic of Pseudomonas spp. It is considered both as a virulence factor and a quorum sensing signalling molecule for P. aeruginosa. Pyocyanin is an electrochemically active metabolite, involved in a variety of significant biological activities including gene expression, maintaining fitness of bacterial cells and biofilm formation. It is also recognised as an electron shuttle for bacterial respiration and as an antibacterial and antifungal agent. This review summarises recent advances of pyocyanin production from P. aeruginosa with special attention to antagonistic property and bio-control activity. The review also covers the challenges and new insights into pyocyanin from P. aeruginosa. PMID- 24214681 TI - Influence of temperature, pH and metal ions on guaiacol oxidation of purified laccase from Leptographium qinlingensis. AB - The bark beetle Dendroctonus armandi is able to kill living Pinus armandi and has caused serious damage to pine forest in Northern China. As the most important symbiotic fungus of D. armandi, Leptographium qinlingensis plays an important role in the invasion process of the bark beetle. The laccase secreted by it are involved in lignin degradation to provide utilizable nutrition for D. armandi, and catalyze some biochemical reactions, causing the damages of tree tissue. In present study, the extracellular laccase of L. qinlingensis was purified by using the ammonium sulfate precipitation and DEAE-cellulose (DE-52) column chromatography. Furthermore, the effects of temperature, pH value and metal ions on it were investigated and characterized. The purified enzyme exerted its optimal activity with guaiacol. The catalytic efficiencies K(m) and V(max) determined for substrate guaiacol were 15.4 MUM and 372.9 IU mg-1, respectively. The optimum pH and temperature for the purified enzyme was 4.4 and 45 degrees C, respectively, with the highest enzyme specific activity of 7,000 IU mg-1. Moreover, the metal ions, Co2+, Mn2+, Ca2+, Mg2+, Fe2+ and Cd2+, especially Hg2+, showed significantly inhibition effects on its activity. To understand the characteristics of this laccase might provide an opportunity and theoretical basis to promote integrated pest management of D. armandi. PMID- 24214682 TI - Duplication of exon 2 of the GPC3 gene in a case of Simpson-Golabi-Behmel syndrome. PMID- 24214683 TI - From opportunism to nascent conservation : The case of the Siona-Secoya. AB - Siona-Secoya hunters of the northwest Amazon strive to maximize short-term yields to provision their households with meat. The observed patterns of hunting more closely resemble the predictions of optimal foraging theory (OFT) than they do a conservation ethic. In the past the Siona-Secoya worried little about conservation because they believed that good shamans attracted abundant game. When hunting was poor, shamans performedyage ceremonies and appealed to supernatural gamekeepers for the release of more animals from the underworld. The sustainability of Siona-Secoya hunting was aided by factors such as low human population density, dispersed settlements within large hunting territories, settlement movement, and limited hunting technology. Today, increasing involvement in the national economy is leading the Siona-Secoya to invest more time in agriculture and wage labor, and less in traditional foraging activities. Colonization, deforestation, and industrial pollution now pose the greatest threats to wildlife in eastern Ecuador. Because of these changes, the Siona Secoya are becoming interested in environmental protection and conservation. Several of their efforts to protect forest resources and mitigate pollution are discussed and evaluated. PMID- 24214684 TI - "Only slaves climb trees" : Revisiting the myth of the ecologically noble savage in Amazonia. AB - Professional and popular publications have increasingly depicted native peoples of Amazonia as "natural" conservationists or as people with an innate "conservation ethic." A few classic examples are cited repeatedly to advance this argument with the result that these cases tend to be generalized to all indigenous peoples. This paper explores the premise that many of these systems of resource conservation come from areas of Amazonia where human survival depends on careful management of the subsistence base and not from a culturally imbedded "conservation ethic." Where resource constraints do not pertain, as in the case of the Yuqui of lowland Bolivia, such patterns are unknown. Finally, the negative consequences of portraying all native peoples as natural conservationists is having some negative consequences in terms of current struggles to obtain indigenous land rights. PMID- 24214680 TI - Composition and variation of sediment bacterial and nirS-harboring bacterial communities at representative sites of the Bohai Gulf coastal zone, China. AB - With rapid urbanization, anthropogenic activities are increasingly influencing the natural environment of the Bohai Bay. In this study, the composition and variation of bacterial and nirS-harboring bacterial communities in the coastal zone sediments of the Bohai Gulf were analyzed using PCR-based clone libraries. A total of 95 genera were detected in the bacterial communities, with Proteobacteria (72.1 %), Acidobacteria (10.5 %), Firmicutes (1.7 %), Bacteroidetes (1.4 %), Chloroflexi (0.7 %) and Planctomycetes (0.7 %) being the dominated phyla. The NirS sequences were divided into nine Clusters (A-I). Canonical correlation analysis showed that the bacterial or denitrifying communities were correlated with different environmental factors, such as total organic carbon, total nitrogen, ammonium, sulfate, etc. Furthermore, bacterial communities' composition and diversity are influenced by oil exploration, sewage discharge and other anthropogenic activities in the coastal area of the Bohai Sea. Thus, this study provided useful information on further research on regional or global environmental control and restore. PMID- 24214685 TI - Aboriginal overkill : The role of Native Americans in structuring western ecosystems. AB - Prior to European influence, predation by Native Americans was the major factor limiting the numbers and distribution of ungulates in the Intermountain West. This hypothesis is based on analyses of (1) the efficiency of Native American predation, including cooperative hunting, use of dogs, food storage, use of nonungulate foods, and hunting methods; (2) optimal-foraging studies; (3) tribal territory boundary zones as prey reservoirs; (4) species ratios, and sex and age of aboriginal ungulate kills; (5) impact of European diseases on aboriginal populations; and (6) synergism between aboriginal and carnivore predation. Native Americans had no effective conservation practices, and the manner in which they harvested ungulates was the exact opposite of any predicted conservation strategy. Native Americans acted in ways that maximized their individual fitness regardless of the impact on the environment. For humans, conservation is seldom an evolutionarily stable strategy. By limiting ungulate numbers and purposefully modifying the vegetation with fire, Native Americans structured entire plant and animal communities. Because ecosystems with native peoples are entirely different than those lacking aboriginal populations, a "hands-off" or "natural regulation" approach by today's land managers will not duplicate the ecological conditions under which those ecosystems developed. The modern concept of wilderness as areas without human influence is a myth. North America was not a "wilderness" waiting to be discovered, instead it was home to tens of millions of aboriginal peoples before European-introduced diseases decimated their numbers. PMID- 24214686 TI - Improving the affinity of an antibody for its antigen via long-range electrostatic interactions. AB - To address how long-range electrostatic force can affect antibody-antigen binding, we focused on the interactions between human cardiac troponin I and its specific single-chain antibodies (scFvs). We first isolated two scFvs against two linear epitopes with distinct isoelectric points. For the scFv against the acidic epitope (A1scFv), we mutated five residues of framework region 3 of the light chain to Lys or Arg, designated as the K- or R-mutant, respectively. For the scFv against the basic epitope (A2scFv), we mutated four or three residues in framework region 3 of the light or heavy chain to Asp, to generate the VL- and VH mutant, respectively. Surface plasmon resonance analyses showed that the kon values of all of the mutants were greater than that of wild type, even though framework region 3 does not make direct contact with the epitope. The affinity of the K-mutant was pM range, and that of the R-mutant improved further by more than two orders of magnitude due to a decrease in the dissociation rate constant. For the A2scFv mutants, the affinity of the VL-mutant for its target improved through an increase in the kon value without a decrease in the koff value. The stability slightly decreased in all mutants. These results suggest that introducing electrostatic interaction can improve the affinity of an antibody for its target, even if the mutation reduces stability of the antibody. PMID- 24214688 TI - Complexes with nitrogen-centered radical ligands: classification, spectroscopic features, reactivity, and catalytic applications. AB - The electronic structure, spectroscopic features, and (catalytic) reactivity of complexes with nitrogen-centered radical ligands are described. Complexes with aminyl ([M(NR2)]), nitrene/imidyl ([M(NR)]), and nitridyl radical ligands ([M(N)]) are detectable and sometimes even isolable species, and despite their radical nature frequently reveal selective reactivity patterns towards a variety of organic substrates. A classification system for complexes with nitrogen centered radical ligands based on their electronic structure leads to their description as one-electron-reduced Fischer-type systems, one-electron-oxidized Schrock-type systems, or systems with a (nearly) covalent M-N pi bond. Experimental data relevant for the assignment of the radical locus (i.e. metal or ligand) are discussed, and the application of complexes with nitrogen-centered radical ligands in the (catalytic) syntheses of nitrogen-containing organic molecules such as aziridines and amines is demonstrated with recent examples. This Review should contribute to a better understanding of the (catalytic) reactivity of nitrogen-centered radical ligands and the role they play in tuning the reactivity of coordination compounds. PMID- 24214687 TI - Proteinuria in preeclampsia from a podocyte injury perspective. AB - Preeclampsia is a frequent cause of maternal and fetal morbidity and mortality worldwide. The underlying causes of this hypertensive complication have remained elusive. The placenta seems to be at the origin of the disease, as its removal appears to be the only effective treatment available. Many organs can potentially be affected. Nonetheless, kidney alterations are always present: proteinuria is one of the hallmarks for a preeclampsia diagnosis. VEGF is pivotal for maintaining glomerular filtration barrier function; hence, the elevated concentrations of placental-derived VEGF inhibitors, such as sFlt-1, may largely explain the renal alterations observed. Classically, glomerular endothelial injury was considered responsible for the renal impairment present in preeclampsia. Recent findings, however, have shown that podocytes are crucial in explaining the loss of filtration capacity of the preeclamptic kidney. The aims of this manuscript are to detail the main findings that associate podocyte injury with proteinuria in preeclampsia, and discuss the eventual applications of podocyte damage biomarkers in clinical practice. PMID- 24214689 TI - Salience of similarity awareness and attraction: A comparison of balance vs reinforcement predictions. AB - Reinforcement and balance theory are both viable explanatory contenders for attraction processes. Differential predictions were derived and tested. Ss rated their attraction toward five strangers who were .00, .25, .50, .75, or 1.00 similax in attitudes. Half of the Ss rated perceived similarity to the strangers prior to making the attraction ratings (similarity]then liking condition) and the other half rated attraction prior to similarity ratings (liking/then similarity condition). Balance theory would predict an interaction between order of rating conditions and proportion of similar attitudes in determining attraction. Results showed that the only significant effect was due to proportion of similar attitudes. Factor analyses of the rating data showed that attraction and similarity ratings loaded on different factors. This result indicates that perceived similarity does not necessarily mediate attraction. Trend analyses suggested that the reverse may hold to some extent; perception of attraction may partially determine perceived similarity. This result suggests that a restricted balance model may be viable. However, the preponderance of the evidence supported reinforcement theory. PMID- 24214691 TI - Frequency and coding responses in verbal discrimination learning. AB - Ss were given a verbal discrimination task where correct and incorrect stimuli appeared in one, two. or four different pairs in a within-Ss design. For a group tested with the usual anticipation procedure, correct repetitions helped and incorrect repetitions hurt performance. The pattern of results suggested that frequency is a salient cue in verbal discrimination learning but that coding or paired-associate processing may occur at the same time. Data from a second group of Ss for which frequency was a less salient cue gave more direct evidence for coding. PMID- 24214690 TI - Feature similarity and feature bias in identification of visually presented letters. AB - Reaction time IRT) to correct identification (ID) was measured for pairs of different letters presented on a memory drum. There were two types of lists. In Type I, visual and name similarity varied orthogonally at two levels. In Type II, one feature was constant at one level, while the other varied at two levels of similarity. For both types of lists, RT is a function of the feature that is more easily extracted from the stimulus. Relative vivaal and name modality biases were estimated, and name bias is relatively more salient than visual bias under these experimental conditions. Specific letters differ in the amount of feature processing required for correct ID and in the relative contribution of visual and name feature effects on this processing. PMID- 24214692 TI - The Declining course of recognition memory. AB - Recognition memory for words can decline, sometimes precipitously, over the course of the recognition test. Decrements of as much as 75% in d' have been observed from the first quarter of testing to the last. and decrements of 40%-50% are not uncommon. Proactive mechanisms, imperfectly understood, appear to underlie such declines: Processing early input renders late input less recognizable, and making early recognition judgments renders later judgments more difficult. At the same time, the processing of late-input words fails to inhibit the recognition of the words that preceded them. PMID- 24214693 TI - Stroop interference with response, comparison, and encoding stages in a sentence picture comparison task. AB - The paper discusses a Stroop variant of the word-picture comparison task analyzed by Chase and Clark (1971). The locatives above or below were printed at the center of a reference square, and Ss reported "Yes" if there was a word or an array of Xs in the location specified and "No" if there was not. Under the control (Xs) conditions, above displays were classified faster than below displays and true displays faster than false displays. These effects were unaltered when the words "yes" or "no" or "right" or "wrong" were printed in place of the Xs, although there was a small overall increase in response latency under these Stroop conditions that was independent of agreement or disagreement between the distractor and the response to be made. When the locatives up and down were printed on the display, a substantial Stroop effect was observed, and the above-below and true-false effects were eliminated. These results are discussed in relation to theories about the nature of Stroop interference and processes involved in sentence-picture comparisons. PMID- 24214694 TI - Sensory stores and high-speed scanning. AB - A model of scanning based on separate sensory and short-term stores was suggested and tested. The experiment used a probe recognition method, with set size varied from 1 to 8 and a fast presentation rate. A masking procedure was used to vary the number of items available in a possible sensory store. Although conditions were such as to maximize the chances of detecting an effect, none was found: the possible size of the sensory store had no effect on reaction time whatsoever. Other aspects of the data lent little support to a serial exhaustive scanning model, but a previously proposed parallel processing model fared better. Finally, not only was the function for positive probes steeper than that for negative probes but also there was a crossover effect as well. This crossover is not without precedent and may indicate the need for consideration of both accuracy and latency in high-speed scanning studies. PMID- 24214695 TI - Comprehension of prenominal adjective orders. AB - In two experiments, phrases descrying a referent object contained two prenominal adjectives in either normal or inverted order. The time to identify the position of the referent in a display was a function of both the adjective order and the nortreferent context. If the referent appeared with a nonreferent differing from it only in size or number, the normal order of adjectives facilitated responding. However. if the referent appeared with a nonreferent differing from it only in color, the inverted order of adjectives resulted in faster identification times. These results support a pragmatic communication rule that. when the more discriminating adjectives are ordered earlier in a series, comprehension is facilitated. PMID- 24214696 TI - Attribution of intention as a function of physiognomy. AB - Ss agree in attributing character traits to strangers' photographs, but there has been no explication of what such labels imply. Presumably. trait names either mediate or reflect Ss' expectations of such strangers" likely social behaviors: but that remains undemonstrated, and we may be able to study such physiognomy tied expectations directly. Sampling problems confront trait studies and intention studies alike, but the present research showed that Ss' expectations of a person's behavioral intentions, as measured by alternative interpretations of short "scenarios," were reliably influenced by that person's photograph. PMID- 24214697 TI - Effects of response requirements on the location of clicks superimposed on sentences. AB - Two methods of identifying the location of clicks superimposed on sentences were compared. When Ss first wrote out the entire sentence and then marked the location of the clicks, the perceived clicks tended to migrate toward the major constituent breaks of the sentences. This trend was not observed when Ss responded by marking the position of clicks on prepared scripts of the stimulus sentence. In addition, both response procedures resulted in a significant trend for the perceived clicks to be located before the actual click locations. The findings of this study resolved the conflicting results obtained from previous investigations in this area. PMID- 24214698 TI - Memory for words recently classified. AB - This paper describes research whose goal is to determine the implications of verba] classificatory, judgments for recognition memory and recall. Toward this end, St were required to answer 100 queries of attribution and superordination ds a TWINGE sudden? Is SPINACH ecstatic? Is a CORKSCREW an opener? Is a DUNGEON a scholar? before being tested unexpectedly on their ability to remember either the uppercase "keywords" or the lowercase "descriptors." Lexical memory did not depend on whether a word had been part of an attributive or a superordinate query. But words from "incongruous" queries almost invariably were more poorly remembered-under conditions of free recall, cued recall, and recognition memory than words from "congruous" queries. Congruous cues, but not incongruous ones, greatly facilitated recall, with keywords being more effective cues than descriptors. Recognition memory of keywords was uniformly superior to that of descriptors. It is argued that the large and pervasive memorial advantages of congruity arise because a congruous query, unlike an incongruous one, fosters a relational encoding of keyword and descriptor. PMID- 24214699 TI - Item concreteness vs spatial organization as predictors of visual imagery. AB - The relative contributions of item concreteness and interitem spatial organization to recall processes were studied by attempting to induce modality specific interference between recall and response. Separate groups of 12 Ss learned lists of items that varied in physical or referential visual characteristics. They later signaled information about them either vocally or via a visually guided response. Some ways of presenting lists for learning that are traditionally regarded as increasing reliance on mediating imagery were effective in generating conflict between recall and the visually guided response. This effectiveness was limited to presentation conditions and list types that introduced spatial organization into the stimulus material. The concreteness of individual items was not useful in predicting visual conflict. PMID- 24214700 TI - Attitudinal maintenance of cognitive categorization. AB - Two experiments were performed that investigated attitudinal influences on cognitive categorization. The studies assessed categorization as a dynamic process with a multiple-sort (MS) technique, having Ss recategorize sentences unti! they ran out of meaningful categories. Condition I allowed Ss to use any dimensions they chose, and Condition It imposed the restraint of the "favorable unfavorable" dimension. No effects of involvement were found when unrestricted sorting was allowed but were found when the evaluative dimension was imposed. There appeared to be a tendency for attitudinal involvement to maintain complexity across sorts. Results were discussed in terms of the influence of dimensions and the possible effects of certain stimulus properties on the maintenance of categorization complexity. PMID- 24214701 TI - Some psycholinguistic aspects of person perception. AB - Adjective-noun combinations in person perception are analyzed from an integration theoretical view, with special reference to judgments of likableness, occupational proficiency, and social value. Different theoretical considerations are shown to apply to these three judgment dimensions, but all can be conceptualized in terms of the valuation and integration operations of integration theory. Experimental support for this conceptual analysis is given for likableness and occupational proficiency. Advantages of the integration theoretical analysis over congruity formulations are pointed out. PMID- 24214702 TI - The attribute selection process in pattern perception: The effect of constraint redundancy and stimulus exposure time on the classification of spatially represented Markov patterns. AB - A transfer paradigm was used to study the effect of constraint redundancy (Rc) and stimulus exposure time (ET) on the "same-different" classifications of pairs of spatially represented Markov patterns (Vargus 7 stimuli; Evans & Mueller, 1966). In the training phase, each S classified, without feedback, pairs of Vargus 7 stimuli generated as deviations from three prototypes (i.e., most probable sequences). Each S received stimuli generated at one of three levels of Rc and exposed for one of three durations. In the test phase, all Ss classified different deviations from the same three prototypes at a single Rc level and a single ET level. Unsupervised classification performance was above chance in both training and transfer and increased slightly over trials. Significant Rc and ET effects were found. These results supported two models of attribute selection and utilization; discussions of these models and their relationships to the findings were directed toward the analysis of the "schema plus correction" hypothesis. PMID- 24214703 TI - Communicator credibility and persuasian. AB - Prior research has usually found a positive relationship between a communicator's perceived credibility and his persuasiveness. An experiment was designed to test the hypothesis that the perceived vested interest of a speaker, the position the speaker advocated, and the social similarity between audience and speaker would influence attributions of credibility and affect the speaker's persuasiveness. Three variables were manipulated in a 2 by 2 by 2 factorial design. Ss read a speech that either favored (pro) or opposed (con) student voting rights; the speech was attributed to a speaker who was either similar (student) or dissimilar (townie) to the stndent audience and who either had a vested interest (running for elective office) or had no vested interest (merely giving his opinion) :in the position he advocated. As predicted, the similarity of the speaker to the audience, the vested interest of the speaker, and the position advocated in the speech strongly influenced attributions of credibility. However, in contrast to much previous research, persuasion was found to be relatively independent of the variation in the speaker's perceived credibility. It was suggested that the failure of attributions of credibility to relate to persuasion may have been due to the high degree of ego involvement for the Ss in the topic of student voting rights. PMID- 24214704 TI - Prevarication: Reasoning from false assumptions. AB - This paper examines the strategies t~sed in solving prevaricative reasoning problems. The task consisted of a noncontradictory set of propositions followed by an assumption that introduced an inconsistency. Ss were required to restore consistency by assigning truth values to propositions. When reasoning from false assumptions, Ss exhibit a specific strategy in assigning truth values: If forced to choose between the truth of a generality (e.g., All As are Bs) and that of a particular fact (e.g., This Y is a Z), the Ss assign the generality TRUE and the fact FALSE. Affirmative generalities are assigned TRUE more often than are negative ones, and those expressing class inclusion are assigned TRUE more often than those expressing property assignment. The data show that the selection of a "path" through this hypothetical reasoning problem cannot be attributed to either the syntactic form or the preexperimental credibility of the propositions. A generality coding model was discussed in terms of strategies sho~ in prevaricative reasoning problems as well as in other inference tasks. PMID- 24214705 TI - Memory in reading and listening to discourse. AB - After reading or listening to short passages, Ss attempted to recognize semantically changed sentences and paraphrases (syntactically and lexically changed sentences). The intervals between the original presentation and test ranged from 1 to 23 sec. In general, paraphrases were poorly detected after a brief time, supporting earlier findings that the exact wording of sentences is not stored in long-term memory. An exception was the high recognition of active passive changes with the visual presentation. Recognition at the first test interval was significantly better after listening than after reading, although the eventual level of recognition memory was not different in the two modes. This result, consistent with other studies of modality effects in short-term memory, suggests that acoustic-phonetic memory played a role in the storage of the auditorally presented material. PMID- 24214706 TI - Perceptual coding strategies in the formation and verification of descriptions. AB - Three experiments were carried out to study the "picture coding" process implicit both in making up descriptions of pictures and in verifying descriptions against pictures. In the first experiment, Ss were asked simply to describe pictures of one object above another; some pictures were symmetrical vertically and some were not. In the other two experiments, other Ss were timed as they judged whether sentences likeStar isn't below line were true or false of such pictures. According to the results, Ss comply to three ordered "preference" rules in describing the two objects, rules that are conditional on characteristics of the picture and demands of the task. Furthermore, Ss in the verification task comply to the same three rules when they view and encode the picturebefore they read the sentence to be verified, but to only one of the rules when they view the pictureafter they read the sentence. The results also reconfirm two recently proposed models for the process of verifying sentences against pictures. PMID- 24214707 TI - Serial position effects for tonal stimuli. AB - Serial position effects for tones were studied in a recognition memory experiment The S was given a stimulus list consisting of several tone bursts followed by a number of test tones. Accuracy of recognition of stimulus items as a function of input position followed the classical bowed serial position curve. Memory strength was a monotonically decreasing function of position in the test list. The data were fitted with a strength theory model of memory. The fit yielded decay parameters corresponding to stimulus- and response-induced interference, which were comparable to the parameters reported for meaningful verbal material. PMID- 24214708 TI - Time to read semantically related sentences*. AB - Ss read sentences specifying relations among concepts, with the sentences related to each other in different hierarchical structures. In the case where sentences had implicative relationships, time to read sentences low in the hierarchy was less if sentences higher in the hierarchy had been read previously, and sentences inconsistent with expectations based on earlier items took longer. However, when structural relations did not involve implication about content, time to read the sentences was not very different regardless of whether related sentences had been read previously. PMID- 24214709 TI - Learning numerical progressions. AB - Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968). PMID- 24214710 TI - Categories, subcategories, and the attenuation of proactive inhibition in free recall. AB - In two experiments, "proactive inhibition" was observed in the free recall of a succession of 15-word lists. Recall performancc declined across lists when all lists were drawn from the same taxonomic category (e.g., occupations). But this decline did not appear when the successive lists were drawn from discrete subcategories (such as "professional" and "skilled manual" occupations). The findings clarify the conditions in which proactive inhibition effects in free recall are likely to occur. Specifically, when the set of items on any one list is more homogeneous than the set of items from all lists taken together, "proactive inhibition" will be attenuated. PMID- 24214711 TI - Context effects in sentence comprehension: A study of the subjective lexicon. AB - These studies explore the role of context in determining what information about the meanings of words is activated in memory at the time a word is encountered in a sentence. Using a color-naming paradigm, it was shown that both meanings of a word that has two distinct meanings are activated in memory at the time the word is heard in a sentence. This activation occurs even when there is sufficient contextual information to indicate which meaning was intended by the speaker. These results support the hypothesis that there exists in memory an isolable subjective lexicon. They suggest that context which is effective in disambiguating lexical ambiguities in the language has its effect only at a relatively late stage in the cognitive processing involved in language comprehension. PMID- 24214712 TI - Reconstructive processes in the free recall of categories. AB - Three experiments, involving three different groups of Ss, were conducted. For each experiment, one group of Ss never saw the stimulus materials but produced "recall outputs" on the basis of someone else's description of the input list. A second group produced a description of, and then recalled, the list, while a third group recalled the list under standard conditions. Each experiment involved different materials: for Experiment I, exhaustive categories were used; for Experiment 11, high-frequency category items were used; and for Experiment III, low-frequency items were used. Results showed all lists were reconstructible with the degree of reconstructibility following the order of experiments. An examination of descriptions produced indicated significant differences between those leading to lengthy outputs and those leading to less extensive outputs; basically, these differed in terms of the degree to which specific information was or was not present in the description. Results were discussed in terms of Bartlett's theory of remembering. PMID- 24214713 TI - Memory load and latency in recognition of pictures. AB - Color photographs of common scenes were used as memory and test items in two memory search experiments. Memory load varied from 2 to 24 items in one experiment and from 4 to 64 in the other. Latency of classification of test items increased with memory load. The increase is verb' close to linear for loads up to six items, but for the full range of memory loads, it is negatively accelerated and approximately logarithmic. Sternberg's (1966, 1969) serial theory of memory search, which predicts linear functions, holds for small memory loads of pictures. If serial search takes place for large memory loads, the speed of search must be faster than for small loads. It is also possible that items in memory loads of all sizes are accessed by a single process that generates a negatively accelerated relation between size of load and latency. PMID- 24214714 TI - A developmental study of the pragmatic communication rule for prenominal adjective ordering*. AB - First-, fourth-, and eighth-grade children and college undergraduates indicated preference for either normal or inverted orders of prenominal adjectives (for example,the large red car or the red large car, respectively) to describe a pictorial referent. Preference for the normal order of adjectives first appeared with the fourth graders. When communication context was vaxied by presenting a nonreferent that required a color adjective for discrimination from the referent, college students increased their preference for the inverted order. This separation of the acquisition of a linguistic rule from its utilization in communication was discussed. PMID- 24214715 TI - Memory and the experience of duration in retrospect. AB - Two experiments investigated the relationship between long-term memory for events occurring during an interval and the experience of duration of the interval in retrospect. In both, Ss attended to a sequence consisting of a standard, an experimental, and a second standard interval. Then unexpected comparative duration and memory judgments were requested. In Experiment I, either 30 or 60 unrelated words occurred during the 180-see experimental interval. When more words had occurred, judgments of duration of the experimental interval, judgments of number of words presented, and number of words recognized all increased, but free recall of words was unaffected. In Experiment II, 80 categorized words occurred during the 160-see experimental interval, with category instances in either blocked or random order. When words were blocked by category, judgments of duration of the experimental interval, free recall, and recognition all increased, but judgments of number of words were unaffected. Results were discussed in terms of Ornstein's (1969) "storage size" hypothesis. PMID- 24214716 TI - The encoding of ignored information. AB - An experiment was conducted to study the dimensions of encoding of verbal material in short-term memory as a function of other demands placed on Ss attention. Eighty Ss shadowed one of two simultaneous lists, under instructions to remember the shadowed or the nonshadowed list, A single recognition probe followed each shadowing trial. Ss judged whether the probed item was (1) identical to, (2) a rhyme of, or (3) a synonym of one of the to be remembered items. Results indicated that acoustic information was encoded from all inputs, regardless of the focus of attention. Evidence for semantic encoding, however, was limited to those conditions in which retention of shadowed material was required. The data were interpreted as contradicting "late selection" theories of attention, which propose that all inputs are analyzed for meaning prior to the focusing of attention. PMID- 24214717 TI - Imagery and sentence mediators in verbal discrimination learning. AB - The effect of instructions to use imagery and sentence strategies in verbal discrimination learning (VDL) was investigated in two experiments. In Experiment I, both imaging to and constructing a sentence for the correct item of each pair facilitated VDL relative to an uninstructed control condition. Incorporating both words of the pair into a compound image or compound sentence had no effect, a result that was replicated in Experiment It. Of the two compound instructions, only compound sentences consistently facilitated associative recall of the VDL pairs, suggesting that compound imagery instructions were not always adhered to by the Ss. PMID- 24214718 TI - A tactile suffix effect. AB - Evidence for a representational tactile memory was obtained from a tactile analogue of the auditory suffix effect. In two experiments, a short sequence of tactile stimuli applied to the fingers was followed by an acoustic (control) or tactile (suffix) recall signal. The serial position curves for the two conditions were compared. They revealed similar and strong primacy effects, but recall of the last few stimuli was higher in the control condition. This terminal control advantage was attributed to the retention of raw tactile information. PMID- 24214719 TI - Effects of search criterion upon unanticipated free recall of categorically related words. AB - Ss determined whether words in a list were members of a relatively general or specific category (e.g., foods vs vegetables), and then they were given an unanticipated free recall test. Assumptions were that: (1) evaluating a word against a general criterion (e.g., food) results in the detection of fewer semantic elements than would evaluating it against a specific criterion (e.g., vegetable), and (2) detecting more semantic elements primes memory. In three studies, free recall scores were highest for the specific search. Instructions to form an image or to think of an association for each word did not improve recall. Telling Ss, just before recall, what categories composed the list increased recall clustering, but not recall. PMID- 24214720 TI - Memory for the intentions of sentences. AB - Memory for the intentions of sentences was studied in two recognition tasks. In each study, Ss first acted out a dialogue written for two people. They then judged whether certain sentences in a second dialogue were the same as or different from previons sentences (Experiment I) or chose between two intentions suggested for some previous sentences (Experiment II) Sentences which were repeated with the same intention across the two dialogues were judged as being the same significantly more often than were sentences repeated with a different intention. The appropriate intention for each of these sentences was also usually chosen. In both studies, Ss appeared to remember more accurately the sentences they had spoken themselves than they did those that were addressed to them. PMID- 24214721 TI - The influence of meaningfulness upon intentional and incidental learning of verbal material. AB - The present investigation concerned the relationship between intentional and incidental learning of verbal material. Both task meaningfulness (sequential dependency of the material) and shifts in performance over time were examined for differential patterns under both types of learning conditions. Cover task performance consisted of the search for typographical errors across four paragraphs of a narrative, learning the recall and recognition of examples of categories of objects in the text. There was lack of support for the argument that incidental and intentional learning represent two distinct types; rather Ss responded similarly to increased task meaningfulness under both learning conditions and evidenced identical performance patterns over time. Results were interpreted within an intentional-attentional hypothesis of incidental learning. PMID- 24214722 TI - The effects of learning instructions and cueing on free recall. AB - Eighty unrelated high-imagery words were presented for free recall learning in groups of four words each. Learning instructions were varied, with one group told to relate the words in each input group by means of images, another group told to use verbal (sentence) mediators, and the control group not given specific learning instructions. During recall, list items were presented as retrieval cues in some conditions. In comparison with the control condition, imagery and verbal mediation instructions produced greater recall, more clustering, and a largez number of instances per group recalled. When the retrieval cues were selected such that one cue came from each of the input groups and when the strength of within-group organization was quite high, Ss recalled more words and a larger number of input groups. It was concluded that instructions and cueing conditions influenced different aspects of the free recall process. Instructions influenced the organization of individual words into units, and cueing affected the retrieval of specific units. PMID- 24214723 TI - Complexity of noninvasive prenatal screening and diagnostic testing for an unbalanced translocation involving chromosomes 5 and 18. PMID- 24214724 TI - Behavioral responses in rats submitted to chronic administration of branched chain amino acids. AB - Maple syrup urine disease (MSUD) is an inborn metabolism error caused by a deficiency of branched-chain alpha-keto acid dehydrogenase complex activity. This blockage leads to an accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their corresponding alpha-keto and alpha-hydroxy acids. Previous reports suggest that MSUD patients are at high risk for chronic neuropsychiatric problems. Therefore, in this study, we assessed variables that suggest depressive-like symptoms (anhedonia as measured by sucrose intake, immobility during the forced swimming test and body and adrenal gland weight) in rats submitted to chronic administration of BCAA during development. Furthermore, we determined if these parameters were sensitive to imipramine and N acetylcysteine/deferoxamine (NAC/DFX). Our results demonstrated that animals subjected to chronic administration of branched-chain amino acids showed a decrease in sucrose intake without significant changes in body weight. We also observed an increase in adrenal gland weight and immobility time during the forced swimming test. However, treatment with imipramine and NAC/DFX reversed these changes in the behavioral tasks. In conclusion, this study demonstrates a link between MSUD and depression in rats. Moreover, this investigation reveals that the antidepressant action of NAC/DFX and imipramine might be associated with their capability to maintain pro-/anti-oxidative homeostasis. PMID- 24214725 TI - Secondary Mitochondrial Respiratory Chain Defect Can Delay Accurate PFIC2 Diagnosis. AB - Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and often result in hepatic failure. There is no gold-standard test for diagnosing mitochondrial disease, and the current diagnosis relies on establishing a consistent pattern of evidence from clinical data, neuroimaging, tissue biopsy, and biochemical investigations. In some patients, the mitochondrial respiratory chain defect (MRCD) diagnosis is confirmed by genetic investigations. In most cases, genetic investigations are not informative and a number of cases remain unexplained.Here, we report on two children presenting with liver disease in whom first investigations suggested MRCD, due to decreased liver respiratory chain activities and decreased mitochondrial DNA copy number. However, sequencing of the genes known to be associated with mitochondrial DNA instability did not identify any pathogenic mutations. Further investigations including exome analysis, biliary bile salt analysis, and/or BSEP immunostaining detected a defect in the bile salt export pump (BSEP). Diagnosis of progressive familial intrahepatic cholestasis type 2 (PFIC2), a hereditary disorder in bile formation due to BSEP deficiency was confirmed by ABCB11 gene sequencing. Deleterious mutations were identified in both patients: one harboring compound heterozygous mutations (p.Arg470*/c.1308+2T>A) and the other homozygous nonsense mutation (p.Tyr354*). This report increases awareness of a possible secondary mitochondrial respiratory chain defect in the liver tissue associated with other underlying causes such as PFIC2. PMID- 24214726 TI - Bisphenol A-associated alterations in the expression and epigenetic regulation of genes encoding xenobiotic metabolizing enzymes in human fetal liver. AB - Alterations in xenobiotic metabolizing enzyme (XME) expression across the life course, along with genetic, nutritional, and environmental regulation, can influence how organisms respond to toxic insults. In this study, we investigated the hypothesis that in utero exposure to the endocrine active compound, bisphenol A (BPA), influences expression and epigenetic regulation of phase I and II XME genes during development. Using healthy 1st to 2nd trimester human fetal liver specimens quantified for internal BPA levels, we examined XME gene expression using PCR Array (n = 8) and RNA-sequencing (n = 12) platforms. Of the greater than 160 XME genes assayed, 2 phase I and 12 phase II genes exhibited significantly reduced expression with higher BPA levels, including isoforms from the carboxylesterase, catechol O-methyltransferase, glutathione S-transferase, sulfotransferase, and UDP-glucuronosyltransferase families. When the promoters of these candidate genes were evaluated in silico, putative binding sites for the E twenty-six (ETS) and activator protein1 (AP1) related transcription factor families were identified and unique to 97% of all candidate transcripts. Interestingly, many ETS binding sites contain cytosine-guanine dinucleotides (CpGs) within their consensus sequences. Thus, quantitative analysis of CpG methylation of three candidate genes was conducted across n = 50 samples. Higher BPA levels were associated with increased site-specific methylation at COMT (P < 0.005) and increased average methylation at SULT2A1 (P < 0.020) promoters. While toxicological studies have traditionally focused on high-dose effects and hormonal receptor mediated regulation, our findings suggest the importance of low dose effects and nonclassical mechanisms of endocrine disruption during development. PMID- 24214727 TI - Neighborhoods and racial/ethnic disparities in adolescent sexual risk behavior. AB - Understanding the determinants of racial/ethnic disparities in adolescent sexual risk behavior is important given its links to the differential risk of teen pregnancy, childbearing, and sexually transmitted infections. This article tests a contextual model that emphasizes the concentration of neighborhood disadvantage in shaping racial/ethnic disparities in sexual risk behavior. We focus on two risk behaviors that are prevalent among Black and Hispanic youth: the initiation of sexual activity in adolescence and the number of sex partners. Using data from the 1997 National Longitudinal Study of Youth (N = 6,985; 48% female; 57% non Hispanic White) evidence indicates that neighborhood disadvantage--measured by concentrated poverty, unemployment rates, and the proportion of female-headed households--partially explains Black and Hispanic disparities from Whites in the odds of adolescent sexual debut, although the prevalence of female-headed households in neighborhoods appears to be the main driver in this domain. Likewise, accounting for neighborhood disadvantage reduces the Black-White and Hispanic-White disparity in the number of sexual partners, although less so relative to sexual debut. We discuss theoretical and practical implications of these findings. PMID- 24214729 TI - Gene network and proteomic analyses of cardiac responses to pathological and physiological stress. AB - BACKGROUND: The molecular mechanisms underlying similarities and differences between physiological and pathological left ventricular hypertrophy (LVH) are of intense interest. Most previous work involved targeted analysis of individual signaling pathways or screening of transcriptomic profiles. We developed a network biology approach using genomic and proteomic data to study the molecular patterns that distinguish pathological and physiological LVH. METHODS AND RESULTS: A network-based analysis using graph theory methods was undertaken on 127 genome-wide expression arrays of in vivo murine LVH. This revealed phenotype specific pathological and physiological gene coexpression networks. Despite >1650 common genes in the 2 networks, network structure is significantly different. This is largely because of rewiring of genes that are differentially coexpressed in the 2 networks; this novel concept of differential wiring was further validated experimentally. Functional analysis of the rewired network revealed several distinct cellular pathways and gene sets. Deeper exploration was undertaken by targeted proteomic analysis of mitochondrial, myofilament, and extracellular subproteomes in pathological LVH. A notable finding was that mRNA protein correlation was greater at the cellular pathway level than for individual loci. CONCLUSIONS: This first combined gene network and proteomic analysis of LVH reveals novel insights into the integrated pathomechanisms that distinguish pathological versus physiological phenotypes. In particular, we identify differential gene wiring as a major distinguishing feature of these phenotypes. This approach provides a platform for the investigation of potentially novel pathways in LVH and offers a freely accessible protocol (http://sites.google.com/site/cardionetworks) for similar analyses in other cardiovascular diseases. PMID- 24214731 TI - Successful outside-the-stent stenting for an occluded primary stented superficial femoral artery. AB - A 61-year-old man with in-stent occlusion of the superficial femoral artery (SFA) underwent the endovascular therapy using a subintimal technique. The wire was intentionally advanced into the subintimal space next to the occluded stent in the SFA, and a stent was implanted in a double barrel fashion outside of the in stent occlusion site. The procedure was performed without any complications and with the successful angiographic and intravascular ultrasound imaging results. At 1-year follow-up, the patient still had no leg complaints and the stent was still shown as patent. The procedure might be a useful technique when the recanalization was proved impossible after several attempts to recanalize the primary occluded stent in the SFA. PMID- 24214732 TI - Synthesis and antioxidant activity of bis and tris heterocycles. AB - A variety of bis heterocycles, oxazolyl/thiazolyl/imidazolyl oxadiazoles having a styryl sulfonylmethyl group at the 5-position of oxadiazole and tris heterocycles having a pyrrolyl/pyrazolyl sulfonylmethyl group at the 5-position of oxadiazole were prepared adopting simple and versatile synthetic methodologies. All the compounds were screened for their antioxidant activities. Compound 5b displayed radical scavenging activity in all the three methods greater than the standard ascorbic acid, whereas compounds 8b and 14b showed activities equal to the standard ascorbic acid. PMID- 24214733 TI - Rhodium(III)-catalyzed intramolecular hydroarylation, amidoarylation, and Heck type reaction: three distinct pathways determined by an amide directing group. PMID- 24214734 TI - Response to chemotherapy in gastric adenocarcinoma with diffusion-weighted MRI and (18) F-FDG-PET/CT: correlation of apparent diffusion coefficient and partial volume corrected standardized uptake value with histological tumor regression grade. AB - PURPOSE: To assess whether changes in diffusion-weighted MRI (DW-MRI) and (18) F fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18) F FDG PET/CT), correlate with treatment response to neoadjuvant therapy (NT), as expressed by tumor regression grade (TRG), from locally advanced gastric adenocarcinoma (GA). MATERIALS AND METHODS: Seventeen patients underwent both DW MRI and (18) F-FDG-PET/CT scans before and after the end of NT. Apparent diffusion coefficient (ADC) and mean standardized uptake value (SUV) corrected for partial volume effect (PVC-SUVBW-mean ) were evaluated and compared with histopathological TRG. RESULTS: Pre- and post-NT and percentage changes for ADC and PVC-SUVBW-mean were assessed. Post-NT ADC and DeltaADC showed a significant inverse correlation with TRG (r = -0.71; P = 0.0011 and r = -0.78; P = 0.00020, respectively) and significant differences in their mean values were found between responders (TRG 1-2-3) and nonresponders (TRG 4-5) (P = 0.0009; P = 0.000082, respectively). No correlations with TRG were found for pre-NT ADC and for all PVC SUVBW-mean values as well as between DeltaADC and Delta PVC-SUVBW-mean . CONCLUSION: DW-MRI seems more accurate than (18) F-FDG-PET/CT and ADC modifications may represent a reproducible tool to assess tumor response for GA. PMID- 24214735 TI - Optimization of iterative reconstruction parameters with attenuation correction, scatter correction and resolution recovery in myocardial perfusion SPECT/CT. AB - OBJECTIVE: The aim of this study was to characterize the optimal reconstruction parameters for ordered-subset expectation maximization (OSEM) with attenuation correction, scatter correction, and depth-dependent resolution recovery (OSEMACSCRR). We assessed the optimal parameters for OSEMACSCRR in an anthropomorphic torso phantom study, and evaluated the validity of the reconstruction parameters in the groups of normal volunteers and patients with abnormal perfusion. METHODS: Images of the anthropomorphic torso phantom, 9 normal volunteers and 7 patients undergoing myocardial perfusion SPECT were acquired with a SPECT/CT scanner. SPECT data comprised a 64*64 matrix with an acquisition pixel size of 6.6 mm. A normalized mean square error (NMSE) of the phantom image was calculated to determine both optimal OSEM update and a full width at half maximum (FWHM) of Gaussian filter. We validated the myocardial count, contrast and noise characteristic for clinical subjects derived from OSEMACSCRR processing. OSEM with depth-dependent resolution recovery (OSEMRR) and filtered back projection (FBP) were simultaneously performed to compare OSEMACSCRR. RESULTS: The combination of OSEMACSCRR with 90-120 OSEM updates and Gaussian filter with 13.2-14.85 mm FWHM yielded low NMSE value in the phantom study. When we used OSEMACSCRR with 120 updates and Gaussian filter with 13.2 mm FWHM in the normal volunteers, myocardial contrast showed significantly higher value than that derived from 120 updates and 14.85 mm FWHM. OSEMACSCRR with the combination of 90-120 OSEM updates and 14.85 mm FWHM produced lowest % root mean square (RMS) noise. Regarding the defect contrast of patients with abnormal perfusion, OSEMACSCRR with the combination of 90-120 OSEM updates and 13.2 mm FWHM produced significantly higher value than that derived from 90-120 OSEM updates and 14.85 mm FWHM. OSEMACSCRR was superior to FBP for the % RMS noise (8.52+/-1.08 vs. 9.55+/-1.71, p=0.02) and defect contrast (0.368+/-0.061 vs. 0.327+/-0.052, p=0.01), respectively. CONCLUSIONS: Clinically optimized the number of OSEM updates and FWHM of Gaussian filter were (1) 120 updates and 13.2 mm, and (2) 90-120 updates and 14.85 mm on the OSEMACSCRR processing, respectively. Further assessment may be required to determine the optimal iterative reconstruction parameters in a larger patient population. PMID- 24214736 TI - The impact of regulatory approval and Medicare coverage on outcomes of carotid stenting. AB - BACKGROUND: Carotid artery stenting (CAS) was introduced in the United States nearly a decade ago as a novel treatment of severe carotid stenosis. Voluminous and high-quality prospective data permit analysis of longitudinal trends in CAS outcomes. METHODS: Outcomes from all prospective trials with the Food and Drug Administration (FDA) oversight from 2000-2011 were reviewed, as were the subset of studies using a single CAS system. All studies shared common inclusion/exclusion criteria, endpoints, independent assessment/adjudication of neurological events, and were conducted in accordance with FDA regulations. Death and stroke (DS) rates from FDA-approved studies in high-surgical-risk patients were assessed. RESULTS: Between 2000 and 2011, two distinct periods with clustered and differentiated outcomes in CAS IDE trials were observed, separated by FDA approval and Centers for Medicare and Medicaid Services (CMS) coverage in 2004-2005. The mean 30-day DS rate in the first wave (2000-2004) of CAS trials was 5.3% (95% CI: 4.6-6.2%), and fell significantly to 2.6% (95% CI: 1.9-3.7%; P = 0.0001) in the second wave (2006-2011). This decline occurred during a simultaneous, independent 24-fold increase in monitored CAS activity. This decline in DS rates was observed in symptomatic and asymptomatic patients, alike independent of device tested. CONCLUSIONS: Declines in periprocedural DS rates in CAS appear linked to regulatory and coverage approvals leading to increased operator experience along with continued regulatory oversight, and provide insight into the introduction of other novel therapies. PMID- 24214728 TI - Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype. AB - Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve. PMID- 24214738 TI - Nanopore-based sequencing and detection of nucleic acids. AB - Nanopore-based techniques, which mimic the functions of natural ion channels, have attracted increasing attention as unique methods for single-molecule detection. The technology allows the real-time, selective, high-throughput analysis of nucleic acids through both biological and solid-state nanopores. In this Minireview, the background and latest progress in nanopore-based sequencing and detection of nucleic acids are summarized, and light is shed on a novel platform for nanopore-based detection. PMID- 24214737 TI - Anatomical features and clinical importance of left atrial diverticula: MDCT findings. AB - To assess the anatomical features and clinical importance of left atrial diverticula and atrial accessory appendages in patients undergoing cardiac computed tomography with multidetector computed tomography. A total of 1305 consecutive patients (385 female, 29.5%; 920 male, 70.5%) were assessed using electrocardiogram-gated computed tomography between May 2010 and June 2013. The anatomical features and the prevalences of left atrial diverticula and left atrial accessory appendages were retrospectively assessed by four radiologists. The relationships between the prevalence and size of the diverticula and the age and gender of the patients were assessed. Among the 1305 patients, 610 (46.7%) exhibited 708 left atrial diverticula, and 62 (4.8%) exhibited left atrial accessory appendages. The most common locations of the left atrial diverticula were the right anterior superior wall (n = 328, 46.3%) and the lateral superior wall (n = 96, 13.5%). In addition to classical cystic and tubular diverticula, 49 (3.7%) of the patients exhibited mixed (cystic-tubular), conical, or hook-shaped diverticula and diverticular forms containing mural calcifications. There was no significant relationship between the prevalence of diverticula and the age and gender of the patients (P > 0.05). In addition to tubular and cystic diverticula, the left atrial wall can host different diverticular forms (such as mixed, conical, calcific, and hook shaped). It could be beneficial to assess the left atrium using MDCT to determine the source of emboli in cryptogenic embolism and to reduce complications associated with interventional procedures performed for left atrial arrhythmias. PMID- 24214739 TI - Application of multiplex SNaPshot assay in measurement of PLAC4 RNA-SNP allelic ratio for noninvasive prenatal detection of trisomy 21. AB - OBJECTIVE: For the samples in which the fetus was heterozygous for the placenta specific 4 (PLAC4) single-nucleotide polymorphism (SNP), our research is to develop a rapid, accurate, and cost-effective assay for the noninvasive prenatal detection of fetal trisomy 21 (T21). METHOD: Maternal plasma samples were prepared from 60 euploid pregnancies (range: 15-23 weeks) to 17 T21 pregnancies (range: 19-26 weeks). With the application of the SNaPshot assay in measuring the PLAC4 RNA-SNP allelic ratio, we can achieve noninvasive prenatal detection of T21. Also we detected the genotypes of SNP located in gene PLAC4 in samples collected in Southeast China of 216 volunteers. RESULTS: Of all 77 singleton pregnancies, 21 gravidas were found heterozygous for the PLAC4 SNP. Among them, four pregnancies with a T21 fetus and 17 pregnancies with a euploid fetus were detected. The SNPs with higher heterozygosity rates on gene PLAC4 were Rs8130833 and Rs4818219, which were estimated to be 0.278 and 0.343, respectively. CONCLUSION: For samples with heterozygous SNPs, the PLAC4 RNA-SNP allelic ratio approach can be used for noninvasive prenatal detection of T21 by the multiplex SNaPshot assay. The two SNPs with higher frequency of heterozygosity on gene PLAC4 were Rs8130833 and Rs4818219 in population of Southeast China. PMID- 24214741 TI - What day is today? An inquiry into the process of time orientation. AB - In each of the 6 work days of a 2-week period, approximately equal numbers of passers-by were presented with the question "What day is today?" The experiment took place in Israel, using a total of 273 Ss. Average RT for the production of a correct response revealed a clear curvilinear relationship with the ordinal position of the day of the week, with longest RTs obtained with midweek target days. Errors revealed a similar curvilinear relationship, being most frequent in the middle of the week. These results are discussed in terms of the utilization of temporal landmarks (e.g., the Sabbath) in the process of time orientation. Additional data regarding the distribution of errors and Ss' introspective reports are presented and speculations regarding the mechanism involved are offered. PMID- 24214742 TI - Two-phase model analysis of the effects of interstimulus interval and masking task in human aversive classical conditioning. AB - Three levels (.5, 1.0, and 2.0 sec) of interstimulus interval (ISI) and presence vs absence of a masking task were manipulated in a human eyelid reflex conditioning situation. Through the use of a two-phase model of conditioning performance, it was concluded that (1) increasing the ISI and introducing a masking task increased the duration of Phase 1, (2) as ISI increased, the amount of conditioning decreased, (3) the trial-by-trial rate of change in response probability increased as a function of ISI, and (4) the masking task reduced operator limits. It was also noted that the typical ISI function is composed of rate effects at short ISis and conditioning limit effects at long ISIs and that the larger 0 at larger ISis does not follow from a model of the stimulus trace hypothesis. PMID- 24214740 TI - Pain and depression: an integrative review of neurobiological and psychological factors. AB - The comorbidity of pain and depression has been well established in the literature and is associated with a greater burden to the individual and society than either condition alone. The relationship between pain and depression is quite complex and multiple factors must be considered when trying to disentangle the pain-depression link including shared neurobiology, precipitating environmental factors and cognitive influences. This article aims to provide an overview of the leading neurobiological and psychosocial theories that have advanced our understanding of the link between pain and depression. To this end we describe the shared neurobiological mechanisms in the brain thought to explain the overlap and consider psychological processes and how they inform a cognitive behavioral model. The article also provides an overview of the evidence based treatment for comorbid pain and depression. PMID- 24214743 TI - Mechanisms of aural encoding: VII. Differences in consonant and vowel recall in a Peterson and Peterson short-term memory paradigm. AB - Ss either saw or heard lists of three syllables which differed by their initial consonant phoneme or their final vowel phoneme. After 5 or 15 sec of mental arithmetic, Ss were required to recall the syllables. Following auditory presentation, vowels were recalled more accurately than consonants in all serial positions and at both delays. In addition, spoken consonants and vowels showed primacy and recency effects. Following visual presentation, consonants and vowels were recalled with equal accuracy at both delays, and no recency effects were observed. These data suggest that superior recall of vowels over consonants results from differential decay of these stimuli in an acoustic storage. These data are consistent with previous experiments showing that, during serial recall, the final vowels in a sequence are recalled more accurately than the final consonants. PMID- 24214744 TI - Effects of percentage occurrence of response members and its method of presentation on verbal discrimination learning and transfer. AB - Each of 144 Ss learned two verbal discrimination (VD) lists for six trials. Two levels of percentage occurrence of response members (100% or 50%) were combined factorially with two methods of presentation and three transfer paradigms (C1-I2, C2-I1, C2-I2). In first-list learning, with one method of presentation in the 50,% ORM entire list was presented with only half the correct (C) items designated on each study trial, while in the second method only half the list was presented with all C items underlined. There were no differences between the two methods in the 100% ORM condition. The results indicated that % ORM was a significant variable in first-list learning, supporting the findings of Newby and Young (1972). No effect was found for method of presentation. Also, no real significant effect of these two variables was found in VD transfer. All results were interpreted in terms of the frequency theory of VD learning. PMID- 24214745 TI - Coding position in a sequence by rhythmic grouping. AB - It has been suggested that a perceived rhythmic organization may mediate remembering musical and other stimuli. This experiment examined whether or not Ss could register and remember position in a sequence using rhythmic grouping. Sixteen Ss heard tapped sequences 24-63 beats long, accented to encourage grouping by 4s. Ss tapped responses revealing whether or not they remembered the sequence length-the last tap's position. Significantly more incorrect responses were off by multiples of 4 beats than by adjacent amounts; these frequent errors of whole rhythmic groups of 4 showed that Ss coded sequence length rhythmically. Ss proved 53% accurate over four response conditions, with individual's scores ranging from 8% to 87%. It was concluded that Ss could count with rhythmic hierarchies, essentially equivalent to counting with a nonstandard number base, to code sequential position. PMID- 24214746 TI - Generation of a pictorial code. AB - In Experiments I and II direct measures were obtained of the time required to convert a picture or a sentence to a report of visualization or to a simple drawing, latencies were faster for pictures than for sentences and were affected by the surface form of the sentence. In Experiment Ill, Ss matched pictures or sentences against a test picture under conditions of simultaneous or successive presentation. "Yes" and "No" response times were affected by sentence form under both conditions, although the difference between sentence-picture and picture picture comparisons was virtually eliminated under the successive condition. In Experiment IV, Ss held a sentence or picture in memory over a 1,500-msec interval at the end of which a test picture or an instruction to draw the design was presented. Construction latencies were shorter in response to pictures than sentences, and there were effects of sentence form on verification time. Some implications of these results are discussed. PMID- 24214747 TI - Invariance of inference time when information was presented in different linguistic formats. AB - Ss read paragraphs varying in syntactic complexity, contiguity of information that was conceptually related, and amount of information relating to quantitative variables. Paragraphs were presented too briefly to allow full reading in many cases. In questions requiring use of the quantitative information, proportion of correct responses was influenced by syntax, contiguity, and number of variables from the paragraph. However, neither syntax nor contiguity influenced latency of correct answers, while number of variables, a factor affecting complexity of the process of answering, did influence correct response latency. The findings confirm and extend earlier results by Kintsch and Monk (1972) and give further support to the proposition that assimilation of information in linguistic input involves storing the semantic content of the message. PMID- 24214748 TI - The total time hypothesis, recall strategies, and memory for rapidly presented word strings. AB - In three experiments the free recall of rapidly presented word strings was studied. The word strings were shown either in grammatical order or a scrambled order. It was found that the invariance of recall with various presentation times for grammatical sequences breaks down at presentation times between 175 and 250 msec. The order of recall, however, remains consistent with the type of sequence presented irrespective of presentation time. The amount of time requked to utilize syntactic information fully in free recall is of approximately the same order of magnitude as that required to read the words. PMID- 24214749 TI - An attribute frequency model for the abstraction of prototypes. AB - An attribute frequency model for the abstraction of prototypes is proposed as an alternative to the prototype-plus-transformation model. A specific model is tested in a Franks and Bransford visual pattern paradigm under conditions in which the two models generate contrasting predictions. The results support the attribute frequency model. Application of the model to reported data obtained in other paradigms is illustrated and discussed. PMID- 24214750 TI - Rule use in character classification: Are serial and parallel processing discrete? AB - Contrary to predictions of a stochastic self-terminating search model, choice reaction times were lower for rulebound positive sets than for nonrulebound positive sets when memory set sizes were varied and stimulus probabilities were held constant. The result suggests that rule use and chunking, as opposed to probability alone, facilitate character classification. As a corollary, it is proposed that serial and parallel processing differ in degree rather than in kind. The extent to which the memory set has been chunked is the critical variable affecting Ss' scanning practices. PMID- 24214751 TI - Retrieval of information from multiple ensembles in short-term memory. AB - A recognition memory experiment investigated Ss' ability to organize information in short-term memory. A paradigm similar to that used by Sternberg was employed. A sequentially presented series of six digits (positive set) was shown with each digit appearing on a red, green, or amber background. The colors defined different ensembles, and responding to a test digit was contingent upon an item's membership in the positive set and the color-defined ensemble. Reaction time (RT) to the test digits indicated that Ss did organize information into ensembles. Furthermore, when informative cues were presented prior to the test item, Ss directed and confined their search to the cued subset. PMID- 24214752 TI - Inhibiting effects of recall. AB - Evidence is reviewed indicating that output interference—the deleterious effects of recall of some information on information recalled later—occurs both in primary and secondary memory. It appears that output interference provides at least a partial account for the disparity between information available in memory and its accessibility at recall. It is argued that consideration of output interference may provide a helpful perspective in resolving problems in the study of episodic and semantic memory, including the negative effects of part-list cueing and the tip-of-the-tongue phenomenon. PMID- 24214753 TI - Stimulus selection and memory strategies in concept problems. AB - Ss were allowed to use zero, one, two, four, or eight markers to signify the category (positive or negative) of previously selected stimuli in an attribute identification problem. The more markers available and used, the fewer trials were required for problem solution. Ss were indifferent to marker valence (positive or negative) in disjunctive problems but showed a definite preference for (the more informative) negative markers in conditionals. Performance of Ss was correlated with their tendency to move markers from lesser to more informative instances. An interpretation of results based on individual differences in information processing activities is suggested. PMID- 24214754 TI - Eye fixations in prediction of recognition and recall. AB - Eye fixations were recorded at viewing of picture-label stimuli presented under either recall or recognition instructions; both retention tests were administered. Ss performed substantially better on the retention test of which they were informed, indicating differential encoding of the same stimuli in anticipation of test type. There was no correlation between recognition and recall of items, evidence that different information from the encoded stimuli was utilized in performing each test. Encoding strategies had no effect on how Ss regarded the stimuli, but viewing patterns were related to memory performance: More word fixations was associated with better verbal recall, while fewer picture fixations was associated with better recall and with better picture recognition. PMID- 24214755 TI - Anchoring and relational judgments by young children and retardates. AB - In five experiments using as dimensions brightness, texture, facial happiness, height, and weight, young children (ages 3.4 to 5.3 years) rendered bipolar judgments of stimuli intermediate in value between alternately given extreme anchors. Consistent relational shifts away from the anchors were found for all dimensions judged, and these effects proved virtually independent of children's ages, the sequential orders of stimulus and anchor presentation, or the provision of overt visual memory props. Evidence of relational judgment within the narrower range of the test stimuli alone was also found. Essentially similar relational judgments were replicated with a sample of severe adult mental retardates. PMID- 24214756 TI - A comparison of the effects of formal similarity among trigrams and among word triads. AB - The central question of this report concerned the role of formal similarity in free recall of lists of trigrams and lists of three-letter word triads. Similarity was manipulated among trigrams by duplicating letters and among triads by duplicating words. An initial study showed that lists of 16 letters were learned more rapidly than a list of 16 three-letter words. Therefore, in the major experiment, the Ss were given all appropriate elements on test trials so that only associative learning was required. Increases in formal similarity caused decreases in rate of learning for both types of lists, and the mechanisms of the interference seemed to be the same for both types of lists, However, the learning of the trigram lists was more rapid than the learning of the triad lists, the difference being maximal with low similarity. PMID- 24214757 TI - Effects of association and repetition in memory for temporal order. AB - Temporal order recognition memory has been examined previously with tasks involving a recency judgment between a pair of items in a preceding string. Recency judgments are impaired when the earlier item is repeated. The present study employed the comparative recency judgment paradigm, with the lists composed of words. The effect of the inclusion in the list of a high associate of the earlier test item was examined and compared to the effect of repetition. Associative interference was observed, but not in all conditions. Direction of association was a significant factor. The results were interpreted in terms of a model of word recognition proposed by Morton. PMID- 24214758 TI - Incentives, information, rehearsal, and the negative recency effect. AB - The negative recency effect is generally attributed to inadequate rehearsal of terminal input items during study. In two experiments, Ss were encouraged to increase rehearsal of initial or terminal input items by offers of incentives for remembering these items and information that there would be a delayed memory test (Experiment I) or by explicit instructions to rehearse terminal items and provision of added rehearsal time (Experiment II). Serial position curves in immediate and delayed recall were little affected by these manipulations. These results are more in line with models that give rehearsal the role of maintaining items in a short-term store than with models that accord rehearsal a role in transfer of information to a more permanent store. PMID- 24214759 TI - The von Restorff effect and measures of organization in normals and retardates. AB - Thirty-two noninstitutionalized retardates and 32 normals of equal mental age (approximately 8 years) heard 10 orders of 10 nouns when the decibel (dB) level of the stimuli was the same and when the dB level of the sixth item was higher. The yon Restorff effect was demonstrated by both groups. The normals' overall recall was superior to that of the retardates' recall. Differences in recall were attributed to the normals' tendency to recall items in the same serial order more consistently. The subjective organization of lists, as measured by order of recall, differed for the normals and retardates; the normal group was more adaptable than the retarded group in adjusting their strategy to different list conditions. PMID- 24214760 TI - Differential effects of repetition on pre- and postcategorical memory traces. AB - The effect of list repetition on immediate recall for aurally presented nine letter lists was studied under two conditions. In the first, a redundant stimulus item was presented as the tenth item in each list, while the suffix was not included in a control condition. As in previous research (Crowder & Morton, 1969), the stimulus suffix selectively interfered with recall at the terminal presentation serial positions, indicating the presence of precategorical acoustic storage. Repetition had a nonselective effect on performance. This result and an analysis of acoustic errors support the inference that qualitative differences in the memory code may lead to differences in other functional properties of the memory trace, such as responsiveness to repetition. PMID- 24214761 TI - Functions of graphemic and phonemic codes in visual word-recognition. AB - Previous investigators have argued that printed words are recognized directly from visual representations and/or phonological representations obtained through phonemic recoding. The present research tested these hypotheses by manipulating graphemic and phonemic relations within various pairs of letter strings. Ss in two experiments classified the pairs as words or nonwords. Reaction times and error rates were relatively small for word pairs (e.g., BRIBE-TRIBE) that were both graphemically, and phonemically similar. Graphemic similarity alone inhibited performance on other word pairs (e.g., COUCH-TOUCH). These and other results suggest that phonological representations play a significant role in visual word recognition and that there is a dependence between successive phonemic-encoding operations. An encoding-bias model is proposed to explain the data. PMID- 24214762 TI - Serial learning: A multilevel access analysis. AB - In Experiment I the lists were 36 and 48 unrelated words. Each was divided into successive groups of four words and learned to a perfect criterion. In Experiment II the lists were made up of six categorical groups of five exemplars each. Degree of learning was varied. In both experiments serial anticipation learning was followed by ordinary free recall and free recall under speed stress. Analyses of acquisition and of both recall tests indicate that group access is a marked function of serial position but that within-group retrieval given group access is constant over serial position. It is argued that serial learning proceeds simultaneously at different levels of representation. PMID- 24214763 TI - Structural descriptions and the limitations of visual images*. AB - Two experiments are reported that require Ss to judge whether or not the second of two sequentially presented patterns is a part of the first pattern. The results suggest that Ss code the pattern as a structural description and find it difficult to recognize a part of the pattern which does not match the description. It is proposed that a structural description is a combination of visual and verbal codes and that visual images lack detail when not supported by verbal concepts. PMID- 24214764 TI - Repetition and practice effects in a lexical decision task. AB - Ss classified visually presented verbal units into the categories "in your vocabulary" or "not in your vocabulary." The primary concern of the experiment was to determine if making a prior decision on a given item affects the latency of a subsequent lexical decision for the same item. Words of both high and low frequency showed a systematic reduction in the latency of a lexical decision as a consequence of prior decisions (priming) but did not show any reduction due to nonspecific practice effects. Nonwords showed no priming effect but did show shorter latencies due to nonspecific practice. The results also indicated that many (at least 36) words can be in the primed state simultaneously and that the effect persists for at least 10 min. The general interpretation was that priming produces an alteration in the representation of a word in memory and can facilitate the terminal portion of the memory search process which is assumed to be random. PMID- 24214765 TI - The retrieval of abstract and concrete materials as functions of imagery, mediation, and mnemonic aids. AB - Department of Educational Psychology, The Pennsylvania State University, University Park, Pennsylvania 16802 This study is a report of an investigation of the interaction between imagery ability and processes employed for facilitating recall. The tasks were assumed to involve contrasting processes through the use of imaginal or verbal mediators and concrete or abstract jingles (mnemonic aids) in memorizing two concrete and two abstract lists of 10 words in each list. The dependent variables were latencies in arriving at an association, number of errors and omissions on immediate recall, and number of errors and omissions on delayed recall. The main effects of imagery ability, favoring high imagers, and of kind of lists favoring concrete lists were significant. In delayed recall there was a significant interaction of mnemonic aid and kind of list. Imagery ability interacted with mediators to influence Ss' recall. The results were discussed as supporting Paivio's two-stage association model. PMID- 24214766 TI - Isolation of items and the stimulus suffix effect. AB - Thirty Ss heard and serially recalled 36 different nine-digit series. The recall cue was a buzzer, the wordzero read in the same voice that read the first seven digits, or the wordzero read in a voice different from the one that read the first seven digits. In half the series, all nine digits were read in the same voice. The final two digits of the remaining series were isolated by having them read in a voice different from the one that read the first seven digits. Zero suffixes disrupted recall of the terminal digits more than the buzzer (the stimulus suffix effect) and had a greater degrading effect when they were in the same voice as the final two digits than when the zero suffixes and the final digits were read in different voices. Isolated digits were more likely to be recalled than nonisolated digits. Results suggest the importance of perceptual analysis in both the stimulus suffix effect and the isolation effect. PMID- 24214767 TI - Attention and memory cues in concept learning as a function of task complexity and age. AB - The effects of attention and memory cues on concept learning performance were investigated as a function of task complexity and grade level of Ss. It was found that: (1) the attention and memory cues were closely interrelated in their effects upon performance with both significantly improving performance at all but the lowest levels of complexity; (2) both types of cues considerably lessened the effect of stimulus complexity upon performance; and (3) the attention cue elicited the best performance from Ss in the first through ninth grades, while the memory cue elicited the best performance from 4-year-old and kindergarten Ss. PMID- 24214768 TI - Retention functions for syntactic and lexical vs semantic information in sentence recognition memory. AB - In a continuous recognition memory design, Ss judged whether each sentence was identical in form and meaning to some previously presented sentence, then judged whether the sentence was identical in meaning irrespective of form, and, finally, rated the likelihood of recognizing the sentence ff it was presented an hour later (memorability). The Ss were given sentences that were new, identical to, or paraphrased from some previously presented sentence, at delays ranging from 0 sec to 2 h. Long-term memory for both semantic information and syntactic-lexical information decayed according to the same exponential-power retention function previously found to be characteristic of the decay of simpler verbal materials (nonsense items, letters, digits, words, and word pairs). Semantic memory primarily differed from syntactic-lexical memory in that the semantic information had a far higher degree of learning, but the decay rate for syntactic-lexical information was also approximately 5 0% greater than the decay rate for semantic information. PMID- 24214769 TI - Implicit alternatives to a stimulus, difficulty of encoding, and schema-plus correction representation. AB - Garner has hypothesized that a S exposed to a stimulus infers alternatives to it. Data are reviewed which establish a close correlation between the number of implicit alternatives to a stimulus and the difficulty of encoding that stimulus. This correlation provides a datum to be explained and suggests that the identification of specific implicit alternatives may provide clues to the encoding process. For dot patterns of a certain kind, it has been suggested that the rotations and reflections of a stimulus are its only alternatives, but a close examination of certain data indicates that, for many of these patterns, the alternatives also include one or more other patterns which differ from the stimulus only in the position of a single dot and which locate that dot in a position where it is more predictable from the other dots. It is suggested that the one-dot-different alternatives represent schemas used in schema-plus correction encoding. PMID- 24214770 TI - Verbal discrimination reversal in a whole/part re-pairing transfer paradigm. AB - Whole/part transfer and re-pairing of rights and wrongs were employed in a study of verbal discrimination reversal learning. The whole/part and re-pairing procedures were used to create reversal conditions (0%, 50%, or 100% reversal) that were similar at the outset of reversal learning in that all correct alternatives on the reversal list were higher in situational frequency than their respective incorrect alternatives. Similarly, reversal lists were constructed that were similar in that all incorrect alternatives on the reversal list were higher in situational frequency than their respective correct alternatives. The results were consistent with the existing literature on verbal discrimination reversal, as performance was impaired when items reversed functions (50% and 100% reversal). There was little evidence that uniform frequency relations between rights and wrongs affected ease of reversal learning. PMID- 24214771 TI - The effect of correlated linguistic dimensions on speeded classification of visually presented trigrams. AB - The influence of two types of linguistic dimensions, word-nonword and consonant pronunciation, on classification speed of trigrams in card-sorting tasks of two levels of complexity was examined. In complex grouping tasks, which required the evaluation of more than one letter to classify each stimulus, sorting times were faster when the linguistic dimension was correlated with, rather than orthogonal to, the response categories. For tasks in which each stimulus could be classified on the basis of a single letter, no effect of the correlated vs orthogonal linguistic dimension was observed, even when performance was degraded by visual noise. These results provide further evidence that, while linguistic properties of visual stimuli may influence classification time in complex tasks, they are of little importance in the performance of tasks only requiring the discriminalion of a single visual feature. PMID- 24214772 TI - Visual recognition memory in reflective and impulsive children. AB - Twenty-nine reflective and 29 impulsive fifth-grade boys were tested in a forced choice visual recognition memory task. In three of the experimental conditions (1FD, 2FD, 4FD) the number of visual feature differences between the correct and incorrect test stimuli was 1, 2, or 4, and correct response could not be based on the name of the stimulus; in the fourth condition (DO) the correct and incorrect test stimuli had different names. As predicted, performance on DO and 4FD was equivalent and was superior to that on 1FD and 2FD. Although reflective Ss made more correct responses than impulsive Ss in all four conditions, only the performance difference in Condition 1FD was significant. Mean correct response latencies mirrored the correct response data. These results were consistent with the Selfridge-Neisser feature-testing model of recognition memory, and it was argued that the primary underlying basis for the dimension of reflection impulsivity was that reflective Ss tend to engage in a more detailed visual feature analysis of stimulus arrays. Strong inferential evidence was provided that visual feature analysis independent of verbal labeling was responsible for successful recognition performance in these Ss. PMID- 24214773 TI - Enactive imagery in paired-associate learning. AB - Three experiments were conducted to study the effects of enactive imagery (EI) on associative learning. In Experiment I, groups of Ss rated 226 verbs on EI and frequency. In Experiments II and III, Ss learned a 24- and a 16-item list, respectively. The lists consisted of the four possible stimulus-response combinations of high (H) and low (L) EI verb pairs: H-H, H-L, L-H, L-L. In both experiments, EI was found to be a significant factor on the stimulus side, performance being superior when the stimulus was of high EI. In Experiment III, the response EI main effect and the Stimulus by Response EI interaction were also found to be significant. The results indicated that like the imagery evoked by nouns, the EI evoked by verbs facilitates learning. PMID- 24214774 TI - Response selection in paired-associate learning. AB - Ss were presented pairs of items on study cycles; on test cycles Ss were presented the stimulus items and required either to recall the correct response or to indicate the correct response from three alternatives. It was demonstrated that Ss who chose the correct responses from the alternatives tended to select from both stimulus and response compounds so that the association was between stimulus and response components. The amount of selection from the response compounds was comparable to that from the stimulus compounds. PMID- 24214775 TI - Discrimination learning as a function of differences in materials: A proposed explanation. AB - The present study affords an explanation for the consistent, but not always statistically significant, pattern showing superior verbal discrimination learning performance for low- as compared to high-frequency words. In a frequency judgment task, it was found that relative to high-frequency words, low-frequency words for which Ss (sixth graders) knew the meanings produced apparent frequency measures consistent with superior verbal discrimination learning, while low frequency words that were unknown to the children did not. These results, taken together with those based on comparisons of pictures and high-frequency words, lend themselves to a modified Weber's law interpretation of stimulus material differences in discrimination learning. PMID- 24214776 TI - First-principles investigation of quantum transport through an endohedral N@C60 in the Coulomb blockade regime. AB - We report an investigation of Coulomb blockade transport through an endohedral N@C60 weakly coupled with aluminum leads, employing the first-principles method combined with the Keldysh non-equilibrium Green's function derived from the equation of motion beyond the Hartree-Fock approximation. The differential conductance characteristics of the molecular device are calculated within the Coulomb blockade regime, which shows the Coulomb diamond as observed experimentally. When the gate voltage is less than that of the degeneracy point, there are two peaks in the differential conductance with an excited state induced by the change of the exchange interaction between the spin of C60 and the encapsulated nitrogen atom due to the transition from N@C(1-)(60) to N@C(2-)(60), while for a gate voltage larger than that of the degeneracy point, no excited state is available due to the quenching of exchange energy. As a result, there is only one Coulomb blockade peak in the differential conductance from the electron tunneling through the highest energy level below the Fermi level. Our first principles results are in good agreement with experimental data obtained by an endohedral N@C60 molecular device. PMID- 24214777 TI - Effects of piperine in experimental intestinal ischemia reperfusion model in rats. AB - BACKGROUND: Piperine is a spice principle, and its protective role against oxidative damage and lipid peroxidation has been reported. In this study, we aimed to investigate the effects of piperine in the prevention of ischemia reperfusion injury to the small intestine. METHODS: Rats were allocated to three groups of 8 rats each. Rats in the sham group underwent laparotomy and observation only. Animals in the control and study groups underwent 45 minutes ischemia followed by 60 minutes reperfusion. In the study group, 10 mg/kg piperine was administered intraperitoneally just before the reperfusion procedure. Blood samples were obtained for measurement of lactate levels, and resection of the terminal ileum was performed to evaluate the histopathologic specimens and tissue malondialdehyde, superoxide dismutase, and glutathione activities. All results were expressed as mean+/-SD. Comparisons between groups were made by using the one way analysis of variance (ANOVA). RESULTS: Lactate and malondialdehyde levels were significantly higher in the control group than the study and sham groups (p<0.001). In the study group, superoxide dismutase, and glutathione activities were significantly higher than in the control group (p<0.001). The sham group had the highest activities. Histopathologic examination showed disruption of villous pattern and lamina propria in the control group. CONCLUSION: Intraperitoneal administration of 10 mg/kg piperine just before the reperfusion may reduce ischemia-reperfusion injury to the small intestine. PMID- 24214778 TI - [The wounding potential of free-falling bullets]. AB - BACKGROUND: It was aimed in this study to clarify the wounding potential of free falling bullets fired at 90 degrees or close to right angles. MEHTOHDS: In this study, 9x19 mm and 7.65x17 mm bullets, which are commonly used among civilians, were used. The muzzle velocities of these ammunitions were measured. According to the muzzle velocity data, the free-falling motion and strike velocity of the 9x19 mm and 7.65x17 mm bullets were simulated using the EBV4(r) External Ballistics Software at angles of 65 degrees -90 degrees with firings at 5 degrees intervals. The simulation results were compared with critical velocity of tissues. In addition, the judicial records and press reports on this type of wound were examined and evaluated in light of the literature. RESULTS: The strike velocity and kinetic energy of free-falling bullets, which were fired into the air at 5 degrees intervals between 65 degrees -90 degrees , were measured. The average strike velocity and kinetic energy of 9x19 mm bullets were 92.25 m/sec and 34.05 J and of 7.65x17 mm bullets were 79.66 m/sec and 14.91 J, respectively. As a result of the archives examination, 65 such wounds were detected between 2000 and 2012, and 27 of them resulted in death. DISCUSSION: According to these results, the strike velocity of free-falling 9x19 mm and 7.65x17 mm bullets, which were fired into the air, exceeds the threshold and critical velocity limits of skin and flat bones, and the kinetic energy of the bullets is able to cause significant wounding. Even though the symptoms and features of these types of wounds may not be similar to those of ordinary gunshot wounds in the first medical examination, the first responders should be aware of the possibility of gunshot wounds, and they should take into account the criminal investigation phase during the treatment process; the necessary precautions should be taken in order to preserve the evidence. PMID- 24214779 TI - Acute pain management with intravenous 0.10 mg/kg vs. 0.15 mg/kg morphine sulfate in limb traumatized patients: a randomized double-blinded placebo-controlled trial. AB - BACKGROUND: We aimed to compare pain relief and safety of two doses of morphine in adult emergency department (ED) patients with acute limb trauma pain. METHODS: A total of 200 adult ED patients over 20 years of age requiring opioid analgesia were randomly allocated to two groups. Following a first dose of intravenous morphine sulfate at 0.10 mg/kg, a randomized double-blind placebo-controlled trial of intravenous morphine sulfate at 0.05 mg/kg versus the same amount of placebo was performed. Measurement of visual analogue scale pain intensity and assessment of adverse effects were performed at baseline (before morphine at 0.10 mg/kg), 30 minutes from baseline (just before study drug administration), and at 60 minutes from baseline (30 minutes after study drug). RESULTS: No significant difference was found between groups at 30 minutes from baseline. There was significant reduction in final pain after 1 hour in the 0.15 mg/kg compared to 0.10 mg/kg group (p<0.05). In addition, there was a significant improvement in the mean score of pain in the same group (p<0.05). The percent of pain reduction in the intervention and control group relative to the basic measures was 52.70% and 35.82%, respectively. Adverse effects were present in both groups; however, there was no statistically significant difference between groups. CONCLUSION: Using two doses of morphine instead of one is a safe and effective method for pain reduction in isolated limb trauma. We recommend performing a second injection of 0.05 mg/kg morphine 30 minutes after the initial standard dose of 0.10 mg/kg to decrease pain in these patients. PMID- 24214781 TI - Microsurgical reconstruction in pediatric patients: a series of 30 patients. AB - BACKGROUND: Free flap surgery in the pediatric population has gained widespread acceptance regarding its technical utility and reliability. Initial concerns as to the feasibility and reliability of the procedure in children were resolved over time. METHODS: Thirty children (15 boys, 15 girls) were treated in Sisli Etfal Training and Research Hospital, Plastic and Reconstructive Surgery Clinic. Their mean age was 10.8 years. Defects were located on the lower extremity (n=22), head and neck (n=5) and upper extremity (n=3). The etiologies of the defects included vehicle accident, sequelae of burn, traumatic contractures, crush injury, epulis in the maxilla, and gunshot wound. RESULTS: The free flaps performed in our series were latissimus dorsi muscle flap, combined latissimus dorsi and serratus muscle flaps, serratus anterior muscle flap, cross latissimus dorsi muscle flap, scapular osteomyocutaneous flap, parascapular fasciocutaneous flap, fibular osteocutaneous flap, anterolateral thigh flap, medial circumflex femoral artery perforator flap, and crista iliaca osteocutaneous flap. CONCLUSION: The advantages of free flaps in children, which include better adaptation of the flap growth and better learning capacity of the children, provide the surgeon with more satisfactory functional and aesthetic results. PMID- 24214780 TI - Management of penetrating injuries of the upper extremities. AB - BACKGROUND: Routine surgical exploration after penetrating upper extremity trauma (PUET) to exclude arterial injury leads to a large number of negative explorations and iatrogenic injuries. Selective non-operative management (SNOM) is gaining in favor for patients with PUET. The present study was undertaken to assess the validity of SNOM in PUET and to present a practical management algorithm. METHODS: All consecutive patients presenting to a tertiary referral center following PUET were included in this prospective observational cohort study. Patients were managed along Advanced Trauma Life Support (ATLS(c)) guidelines, and based on clinical manifestations, either underwent emergency surgery or were treated conservatively with or without additional diagnostic investigations. Computed tomography angiography (CTA) was indicated by a preset protocol based on the physical examination. RESULTS: During the four-month study period, 161 patients with PUET were admitted. Sixteen (9.9%) patients underwent emergency surgery, revealing 14 vascular injuries. Another 8 (5.0%) patients underwent vascular exploration following CTA. The remaining patients (n=137) were managed non-operatively for vascular matters. Eighteen (11.2%) patients required semi-elective surgical intervention for fractures or nerve injuries. During the follow- up, no missed vascular injuries were detected. CONCLUSION: Neither routine exploration nor routine CTA is indicated after PUET. Stable patients should undergo additional investigation based on clinical findings only. SNOM is a feasible and safe strategy after PUET. PMID- 24214782 TI - Epidemiologic and clinical characteristics and outcomes of scorpion sting in the southeastern region of Turkey. AB - BACKGROUND: Scorpion sting resulting in envenomation is a life-threatening emergency and causes serious health problems in tropical and subtropical regions. The aim of this study was to present the epidemiologic and clinical features of 123 cases presenting with symptoms of scorpion poisoning, a cause of preventable mortality and morbidity. METHODS: This study retrospectively analyzed the epidemiologic and demographic features of a total of 123 patients who presented to Diyarbakir State Hospital Emergency Service with scorpion sting between January 2008 and December 2009. RESULTS: Among 123 patients who presented to Diyarbakir State Hospital Emergency Service with scorpion sting between January 2008 and January 2009, 62.6% (n=77) were female and 37.4% (n=46) were male. The mean age of the patients was 33.5+/-17.3 years (2-80), and 27 (22%) patients were younger than 18 years. The place of residence was rural region in 98 (79.7%) patients and the city center in 25 (20.3%). The majority of victims were stung by scorpions while they were at active work (42.3%) or asleep (19.5%) in bed. Eleven (8.95%) patients were stung by a scorpion while putting on their own clothes. CONCLUSION: This simple descriptive study will hopefully help healthcare providers take measures to prevent scorpion stings, which should take into consideration local epidemiological features. PMID- 24214783 TI - Details of motorcycle accidents and their impact on healthcare costs. AB - BACKGROUND: Of overall traffic accidents in 2011 in Turkey, 7.58% (n=21,107) were motorcycle accidents. Motorcycle accidents and their impact on healthcare costs are investigated in our study. METHODS: Motorcycle accidents that occurred with/without a collision between 1 July 2010 and 30 June 2011 were studied prospectively through the inspection of patients visiting the Emergency Service. The healthcare costs relevant to each person injured in a motorcycle accident were investigated via forms. Data were analyzed using frequencies, Kolmogorov Smirnov, Mann-Whitney U, and chi-square tests on the SPSS v16.0 program. RESULTS: Ninety-one people involved in accidents, with a mean age of 28.47 years, were studied. The average healthcare expenditure for the 91 patients studied between reception and discharge was US$253.02 (median, US$55.90; range, US$11.52 - 7137.19). According to our study, there was no definitive correlation between the healthcare costs and the time of the accident, motorcycle type, nature of the road surface, protective equipment, weather, or daylight. CONCLUSION: According to the current study, the risk of an accident increases with young adults. Concordantly, healthcare costs increase. Thus, it is important that the legal rules with respect to the age and education necessary for receiving a license to operate a motorcycle should be redefined, and if necessary, regulated. PMID- 24214784 TI - The reflection of the Syrian civil war on the emergency department and assessment of hospital costs. AB - BACKGROUND: In the present study, it was aimed to assess the demographics, clinical features, and treatment costs of cases referred to our hospital after the Syrian civil war. METHODS: Of 1355 Syrian civil war victims referred to our hospital during the 14-month period between June 2011 and July 2012, 482 cases presenting to the emergency department were included in the study. The electronic data of these patients were retrospectively analyzed. RESULTS: Of 482 cases, 428 were male (88.8%) and 54 (11.2%) were female, with a mean age of 30.4+/-14.9 years (1-79 years). The mean age was 30.8+/-17.2 years (1-79 years) in males and 27.3+/-16.9 years (1.5-66 years) in females. There was a significant difference in terms of sex (p=0.007). It was found that the majority of the cases (41.1%) were aged 21-30 years. The highest number of admissions was recorded in June 2011 (159 patients, 33%), whereas the lowest number of admissions was in September 2011 (5 patients, 1%). All cases were transported to our hospital from nearby district hospitals and camps by emergency medical services. The most frequent presenting complaint was gunshot injury (338 cases, 70.1%). The most common diagnosis was extremity injury (153 cases, 31.7%). The number of forensic cases was found as 364 (75.5%). Of all the cases, 136 cases (28.2%) were managed in the emergency service, and the remaining cases were admitted to other services. They were most frequently admitted to the orthopedics ward (146 cases, 30.3%). The mean length of the hospital stay was 9.9 days (1-141).Overall, 456 cases (94.6%) were discharged, 22 cases died, and 4 cases were transferred to other facilities. The mean cost per case was estimated as 3723Turkish lira (TL) (15-69556). A positive correlation was found between cost and length of hospital stay. CONCLUSION: Among all Syrian cases, the majorities of young males and gunshot injuries was striking. Most of the cases were discharged after appropriate management. Preventive measures can avoid these negative outcomes and so avoidable costs will not occur, and this can preclude the damage to the budgets of the countries. PMID- 24214785 TI - The synergy between endoscopic assistance and extraoral approach in subcondylar fracture repair: a report of 13 cases. AB - BACKGROUND: We aimed to present the primary experience of one surgeon with a new surgical technique performed on the first 13 cases and to evaluate outcomes following an extraoral endoscopic approach to subcondylar fractures. METHODS: Fifteen subcondylar fractures in 13 patients, who were treated at Ondokuz Mayis University Hospital between January 2010 and June 2011, were included in this study. Patients were operated on using either endoscopic or open approach. RESULTS: Rigid plate fixation was completed endoscopically using extraoral approach in nine fractures, while six fractures were plated by conversion to a full-open approach. In all six fractures that could not be fixed endoscopically, the proximal fragments were medially displaced, whereas seven of nine fractures that were successfully fixed endoscopically were laterally displaced. CONCLUSION: An extraoral endoscopic approach for subcondylar fractures is feasible and can be carried out with decreased morbidity. This approach is recommended for those with limited experience in endoscopy to treat low laterally displaced subcondylar fractures as their initial cases. PMID- 24214786 TI - Three-year experience in the Emergency Department: the approach to patients with spinal trauma and their prognosis. AB - BACKGROUND: Spinal cord injuries result in critical pecuniary and/or non pecuniary losses due to the developing neurological problems. The objective of this study was to evaluate spinal injuries in terms of clinical severity and prognosis. Spinal injuries lead to serious clinical results due to the high rates of morbidity and mortality; however, there is a lack of reliable information on spinal injuries in our country. METHODS: Following the approval of the Faculty Ethics Committee, this retrospective study was conducted on 91 patients aged ?18 (59 male, 32 female) with spinal trauma who were admitted to the Emergency Department of Ondokuz Mayis University over three years. The patients were assessed in terms of demographics, clinical severity, developing complications, and mortality. RESULTS: Forty-three patients had complete injuries, while 48 had incomplete injuries. Forty-six patients suffered spinal injuries due to fall from height, 35 patients due to traffic accidents, and 10 patients due to other reasons. Several complications were observed in 52 patients, while no complication occurred in 39 patients. We determined that 19 of 92 patients involved in this study died, while 72 were discharged from the hospital. CONCLUSION: Spinal cord injuries generally result in unfavorable clinical results. Therefore, an appropriate approach (early diagnosis and true treatment) in emergency services has great significance. PMID- 24214787 TI - Retrospective analysis of 132 patients with orbital fracture. AB - BACKGROUND: The aim of this study was to evaluate the clinical and epidemiological features of 132 patients with orbital wall fracture who were treated at Sisli Etfal Teaching and Research Hospital, Istanbul, between 2005 2012. METHODS: The medical records of the patients with a diagnosis of orbital fracture were reviewed and analyzed. The patients were evaluated by age, gender, etiology, symptoms, examination findings, fracture location, associated injuries, treatment, and complications. RESULTS: The mean follow-up time was 9 (6-16) months. The male-to-female ratio was 5.3-1. The average age was 32 (6-82) years. The leading causes of orbital fractures were traffic accidents (36%) followed by assaults (32%). The most frequently affected orbital wall was the medial wall (33%). The main symptom was throbbing pain in the traumatized area (100%), and the main examination finding was periorbital edema and ecchymosis (100%). The most frequent associated injury was cerebral trauma (14%). Sixty-seven patients (50.1%) were managed with medical treatment, and 65 patients (49.9%) underwent surgical treatment. The most common complication in the late period was dermatomal sensory loss (11%). CONCLUSION: This study makes clear that the frequency of orbital injuries may be decreased by preventing traffic accidents, by taking precautions in the event they occur, and by promulgating social and educational work against violence. PMID- 24214788 TI - [Results of anterior and posterior capsular approaches in bipolar hemiarthroplasty patients with femoral neck fractures]. AB - BACKGROUND: We evaluated the functional status and postoperative complications of bipolar hemiarthroplasty patients with femoral neck fractures, which we operated using anterior and posterior approaches. MEHTOHDS: Between November 2007 and February 2011, 224 patients were evaluated according to their surgical exposure type in two groups. The first group, which was approached anteriorly to the joint capsule, included 92 patients, and the second group, approached posteriorly, included 132 patients. The mean follow-up period for group 1 was 16.4 months and for group 2 was 18.9 months. RESULTS: Harris hip score of group 1 was 81.7 and of group 2 was 79.2. In group 1, 19 patients had very good, 52 patients good, 15 patients moderate, and 6 patients insufficient results. In group 2, 29 patients had very good, 74 patients good, 21 patients moderate, and 8 patients insufficient results. Although we had higher hip dislocation and infection rates in group 2, there were no statistical differences between the two groups. DISCUSSION: Surgical exposure type does not affect functional outcome in bipolar hip arthroplasty patients. Although statistically insignificant, we had higher hip dislocation and infection rates using the posterior approach in the selected femoral neck fracture patients. An anterior approach to the joint capsule appears to be more reliable. PMID- 24214789 TI - [General approach to penetrating abdominal traumas of Turkish general surgeons: survey of practice]. AB - BACKGROUND: In patients with penetrating abdominal traumas (PATs), selective non operative management (SNOM) has been widely accepted. This study was designed to investigate the practice trends among Turkish surgeons regarding SNOM. MEHTOHDS: The study was conducted as an online survey. Participants' demographic characteristics and their management trends and opinions regarding patients with PATs and SNOM were studied. Data were recorded using MS Excel(r) and analyzed. RESULTS: A total of 180 surgeons participated in the survey. SNOM approach rate in patients with stab injuries (SI) was 64%, whereas in patients with gunshot injuries (GSI), this rate was 52%. However, more than 90% of the surgeons declared that additional diagnostic studies were required before selecting SNOM approach in both SI and GSI. In addition, most of the surgeons who did not use SNOM in practice reported that they did not want to risk the patients' lives or their careers. DISCUSSION: Although our surgeons have constructive opinions and tendencies regarding contemporary approaches in the management of PATs, it is seen that nearly half of them prefer not to perform SNOM in practice for various reasons. We believe that approval of trauma and emergency surgery disciplines as subspecialties and funding- centralized trauma centers might correct this deficiency. PMID- 24214790 TI - Emergency abdominal surgery in a patient anticoagulated with dabigatran. AB - Dabigatran is a newer oral anticoagulant, indicated for chronic atrial fibrillation anticoagulation. Experience with an emergent laparotomy in a patient on dabigatran is presented. Difficulties of this medication and strategies to deal with the coagulopathy from this direct thrombin inhibitor are described. PMID- 24214791 TI - Posttraumatic tricuspid valve injury and severe tricuspid valve regurgitation. AB - A 66-year-old male was brought to our hospital following a car accident. He had subarachnoid hemorrhage, multiple rib fractures, and left hemopneumothorax. He was referred to the Cardiology Department for elevated troponin levels (42 ng/ml, reference 0-1 ng/ml). The electrocardiogram was free of ischemia, whereas the transthoracic echocardiography revealed dilated right heart chambers, enlarged tricuspid annulus and coaptation failure of the tricuspid valvular leaflets. There was rupture on the subvalvular apparatus of the anterior leaflet of the tricuspid valve with accompanying prolapse, causing severe tricuspid valvular regurgitation. The patient did not present right ventricular failure signs and symptoms; he was referred to surgery after the resolution of associated thoracic and cranial injuries. PMID- 24214792 TI - A case report of multiple fractures with arterial vasospasm associated with ergotamine use. AB - Vasospasm that develops in association with ergotamine use is a rarely seen but well-understood complication. A case is presented here of multiple fractures in which arteriospasm affecting all the arteries of the lower limb on the same side occurred 10 days post-trauma. In this case, the arteriospasm resulting from ergotamine addiction and high doses of ergotamine, which may be confused with post-traumatic angiospasm, was treated with a marcaine infusion by epidural catheter and heparin, iliomedin and nitronal infusion intravenously. This clinical condition should be borne in mind for all trauma cases determined to have arterial vasospasm, and the use of ergotamine must be queried when taking the anamnesis from the patient. PMID- 24214793 TI - Hepatic duct confluence injury in blunt abdominal trauma - a diagnostic dilemma. AB - Isolated hepatic duct confluence injury due to trauma is unusual. Two cases of isolated bile duct injury are presented, which were diagnosed and managed successfully at our institution. PMID- 24214794 TI - Long-term follow-up results of a pediatric brachial plexus laceration. AB - A rare case of pediatric brachial plexus laceration is presented. A five-year-old boy who sustained a sharp laceration on his right axillary region was immediately operated. The axillary artery, radial, ulnar and musculocutaneous nerve branches of the brachial plexus, and the lateral root of the median nerve were totally lacerated. The medial root of the median nerve was partially transected. All of the lacerated brachial plexus elements and axillary artery were immediately repaired. Significant functional recovery was determined even six months after the repair. Motor and sensory functions of the affected extremity were almost totally restored at the postoperative 21st month, except for the ulnar nerve motor functions. There was no cold intolerance or trophic change at the injured extremity. Primary repair of a brachial plexus laceration injury in the pediatric population can be expected to produce successful functional recovery results, even in a relatively short period after the repair. PMID- 24214795 TI - [Should appendectomy be performed in Amyand's hernia?: two case reports]. AB - The presence of appendix vermiformis in an inguinal hernia sac is called Amyand's hernia. The disease is named after Claudius Amyand, who performed the first documented and successful appendectomy during a hernioplasty in 1975. Finding an appendix within an inguinal hernia is reported at a rate of 0.51%-1% in the adult population, whereas there is no reported frequency of Amyand's hernia in children due to its rare occurrence. Here, we report two cases of Amyand's hernia. The first is a newborn, diagnosed with strangulated Amyand's hernia by preoperative ultrasound examination of the groin. In this case, the appendix had compromised blood supply, so we performed appendectomy during the hernioplasty. The second patient was diagnosed with Amyand's hernia during elective hernioplasty. In this case, the appendix had no evidence of circulatory or inflammatory disorders, so we performed simple hernioplasty and left the appendix in the abdominal cavity. In Amyand's hernia, there are no standards in approaching the appendix. Appendectomy is not a necessity unless there are circulatory or inflammatory injuries. PMID- 24214797 TI - The impact of facecards on patients' knowledge, satisfaction, trust, and agreement with hospital physicians: a pilot study. AB - BACKGROUND: Simple interventions such as facecards can improve patients' knowledge of names and roles of hospital physicians, but the effect on other aspects of the patient-physician relationship is not clear. OBJECTIVE: To pilot an intervention to improve familiarity with physicians and assess its potential to improve patients' satisfaction, trust, and agreement with physicians. DESIGN: Cluster randomized controlled trial assessing the impact of physician facecards. Physician facecards included pictures of physicians and descriptions of their roles. We performed structured interviews of randomly selected patients to assess outcomes. SETTING: One of 2 similar hospitalist units and 1 of 2 teaching-service units in a large teaching hospital were randomly selected to implement the intervention. MEASUREMENTS: Satisfaction with physician communication and overall hospital care was assessed using the Hospital Consumer Assessment of Healthcare Providers and Systems. Trust and agreement were each assessed through instruments used in prior research. RESULTS: Overall, 138 patients completed interviews, with no differences in age, sex, or race between those receiving facecards and those not. More patients who received facecards correctly identified >=1 hospital physician (89.1% vs 51.1%; P < 0.01) and their role (67.4% vs 16.3%; P < 0.01) than patients who had not received facecards. Patients had high baseline levels of satisfaction, trust, and agreement with hospital physicians, and we found no significant differences with the use of facecards. CONCLUSIONS: Physician facecards improved patients' knowledge of the names and roles of hospital physicians. Larger studies are needed to assess the impact on satisfaction, trust, and agreement with physicians. PMID- 24214796 TI - Prevalence, patterns and predictors of nursing care left undone in European hospitals: results from the multicountry cross-sectional RN4CAST study. AB - BACKGROUND: Little is known of the extent to which nursing-care tasks are left undone as an international phenomenon. AIM: The aim of this study is to describe the prevalence and patterns of nursing care left undone across European hospitals and explore its associations with nurse-related organisational factors. METHODS: Data were collected from 33 659 nurses in 488 hospitals across 12 European countries for a large multicountry cross-sectional study. RESULTS: Across European hospitals, the most frequent nursing care activities left undone included 'Comfort/talk with patients' (53%), 'Developing or updating nursing care plans/care pathways' (42%) and 'Educating patients and families' (41%). In hospitals with more favourable work environments (B=-2.19; p<0.0001), lower patient to nurse ratios (B=0.09; p<0.0001), and lower proportions of nurses carrying out non-nursing tasks frequently (B=2.18; p<0.0001), fewer nurses reported leaving nursing care undone. CONCLUSIONS: Nursing care left undone was prevalent across all European countries and was associated with nurse-related organisational factors. We discovered similar patterns of nursing care left undone across a cross-section of European hospitals, suggesting that nurses develop informal task hierarchies to facilitate important patient-care decisions. Further research on the impact of nursing care left undone for patient outcomes and nurse well-being is required. PMID- 24214798 TI - Cultured beef: medical technology to produce food. PMID- 24214799 TI - Anticancer bioactive peptide-3 inhibits human gastric cancer growth by suppressing gastric cancer stem cells. AB - In the present study, the effective components of anticancer bioactive peptide-3 (ACBP-3), a novel antitumor agent isolated from goat liver, were analyzed. The CD44 (+) fraction of the human gastric cancer cell line was isolated, and the cells within this fraction that could form spheroid colonies (SCs) were identified as gastric cancer stem cells (GCSCs). Subsequently, the antitumor effect of ACBP-3 on GCSCs was investigated in vitro and in vivo. ACBP-3 dose dependently decreased the percentage of CD44 (+) cells, suppressed the proliferation of the SC cells and inhibited their clone-forming capacity. Tumor formation from inoculated SC cells took substantially longer when the cells were treated with ACBP-3 in vivo. ACBP-3 alone or in combination with cisplatin suppressed xenograft tumor growth. The antitumor efficacy of cisplatin, when combined with ACBP-3, was enhanced even using half of the normal cisplatin dosage. The combination of cisplatin and ACBP-3 could partially alleviate the body weight loss in the mice. Moreover, treatment with ACBP-3 alone could prevent the body weight loss in the mice. Our study indicated that ACBP-3 inhibited gastric cancer cell growth by suppressing the proliferation of CSCs. ACBP-3 could be a potential CSC-targeting agent, and combined with cisplatin therapy, might be an effective way to clinically treat patients with cancer with a lower dose and reduced toxicity. PMID- 24214800 TI - A framework for the study of filial imprinting and the development of attachment. AB - Filial imprinting is the process through which early attachment behavior becomes restricted to the mother and siblings. In the present paper it will be shown that the processes underlying imprinting in chicks (Gallus gallus) can be fruitfully analyzed by referring to the same mechanisms as are generally assumed to play a role in perceptual and associative learning. This can be achieved within a framework formulated to study the development of behavior in general. This offers the opportunity to apply the same general framework to the study of filial imprinting and the further development of attachment. The involvement of perceptual and associative processes in imprinting is discussed in some detail, while the broader implications of the present approach are indicated only briefly. PMID- 24214801 TI - Brain size and cognitive ability: Correlations with age, sex, social class, and race. AB - Using data from magnetic resonance imaging (MRI), autopsy, endocranial measurements, and other techniques, we show that (1) brain size is correlated with cognitive ability about .44 using MRI; (2) brain size varies by age, sex, social class, and race; and (3) cognitive ability varies by age, sex, social class, and race. Brain size and cognitive ability show a curvilinear relation with age, increasing to young adulthood and then decreasing; increasing from women to men; increasing with socioeconomic status; and increasing from Africans to Europeans to Asians. Although only further research can determine if such correlations represent cause and effect, it is clear that the direction of the brain-size/cognitive-ability relationships described by Paul Broca (1824-1880), Francis Galton (1822-1911), and other nineteenth-century visionaries is true, and that the null hypothesis of no relation, strongly advocated over the last half century, is false. PMID- 24214802 TI - Global matching models of recognition memory: How the models match the data. AB - We present a review of global matching models of recognition memory, describing their theoretical origins and fundamental assumptions, focusing on two defining properties: (1) recognition is based solely on familiarity due to a match of test items to memory at a global level, and (2) multiple cues are combined interactively. We evaluate the models against relevant data bearing on issues including the representation of associative information, differences in verbal and environmental context effects, list-length, list-strength, and global similarity effects, and ROC functions. Two main modifications to the models are discussed: one based on the representation of associative information, and the other based on the addition of recall-like retrieval mechanisms. PMID- 24214803 TI - Heuristics and invariants in dynamic event perception: Immunized concepts or nonstatements? AB - There is ample evidence showing that observers are able to judge dynamic properties of moving objects on the basis of visual kinematics. It is, however, widely disputed as to how to explain this body of data. While direct perceptionists claim that observers have direct access to the underlying dynamics of the event (kinematic specification of dynamics, or KSD, principle), contenders of the perceptual heuristics approach (PH) suggest that observers use the visual equivalent of a heuristic to arrive at their judgments about dynamics. First, the critical assumptions of the KSD principle are discussed in order to motivate the claim that the KSD principle cannot be falsified and is thus immune to empirical criticism. Then the same scrutiny is applied to the PH approach. It is, in its general form at least, afflicted with a similar lack of falsifiability. In comparing the concepts underlying invariants and perceptual heuristics, my conclusion is that a critical experiment aimed at deciding between the two approaches is impossible, and that KSD and PH can be regarded as nonstatements. The findings reported in the event-perception literature must therefore be reevaluated on these grounds. PMID- 24214804 TI - Evidence that blocking is due to associative deficit: Blocking history affects the degree of subsequent associative competition. AB - Rats were trained on an appetitive discriminated operant procedure according to a blocking design, in which training with a compound stimulus (A + B) was given with or without prior training with A alone. Stimulus B was then presented in compound with a new stimulus (B + C compound). The ability of Stimulus B to block acquisition of control by Stimulus C was decreased by B having itself been blocked by A during the prior training. The results imply that the mechanism of blocking during the initial blocking procedure was a reduced association between Stimulus B and the reinforcer, and not a performance deficit such as that postulated by comparator models of learning. PMID- 24214805 TI - Late influences on perceptual grouping: Amodal completion. AB - Perceptual grouping is generally assumed to be an early visual process that operates on a previously unorganized image-based representation. The present experiment shows that elements perceived as occluded by a closer surface tend to be grouped with elements having the same shape as the amodally completed percept rather than with those having the same retinal shape as the incomplete stimulus. It is therefore concluded that perceptual grouping by shape similarity either occurs after amodal completion or is a temporally extended process that occurs both before and after it. PMID- 24214806 TI - Spatial cuing in a stereoscopic display: Evidence for a "depth-blind" attentional spotlight. AB - This experiment explored whether attentional selection observed in a spatial cuing task is based on a representation that includes depth information or not. Targets were presented inside placeholders appearing at the samex,y location on a stereoscopic display, but on different depth planes, or at differentx,y locations on the same depth plane. A peripheral precue produced significant cuing effects in the latter but not in the former condition. In a control experiment, significant cuing effects were found for targets appearing at differentx,y coordinates within the fovea, confirming that the lack of cuing effects in the depth condition was not due to foveal presentation. Together, the results suggest that spatial selection in spatial cuing tasks operates on a representation that does not include depth information. PMID- 24214807 TI - Varieties of positive and negative priming. AB - Numerous recent investigations have focused on a particular relation between the roles a stimulus plays in successive displays: when a stimulus ignored by a subject on one occasion is to be attended on a succeeding occasion, reaction time to that stimulus is slowed relative to a control condition. But this is but one possible case ofnegative priming. There are other ways in which negative priming might occur, and there are several varieties of positive priming as well. All these possibilities were explored in the present experiment. PMID- 24214808 TI - Does negative priming imply preselective identification of irrelevant stimuli? AB - Responses to recently ignored stimuli are often slower than responses to new stimuli (negative priming). This slowing is thought to imply that the irrelevant stimuli were identified before the relevant stimuli were selected. The slowing may, however, reflect processing that occurred after the selection process had already begun. In two experiments, the opportunity for preselective identification of irrelevant stimuli was eliminated by presenting the irrelevant stimuli late within the trial. Negative priming failed to occur under these conditions. PMID- 24214809 TI - Induction and category coherence. AB - In studies of category formation, subjects rarely construct family resemblance categories. Instead, they divide objects into categories using a single dimension. This is a puzzling result given the widely accepted view that natural categories are organized in terms of a family resemblance principle. The observation that natural categories support inductive inferences is used here to test the hypothesis that family resemblance categories would be constructed if stimuli were first used to generate inductive inferences. In two experiments, subjects answered either induction questions, which made interproperty relationships more salient, or frequency questions, which required information only about individual properties, before they performed a sorting task. Subjects were likely to produce family resemblance sorts if they had first answered induction questions but not if they had answered frequency questions. PMID- 24214810 TI - Delay-discounting probabilistic rewards: Rates decrease as amounts increase. AB - The independence of delay-discounting rate and monetary reward size was tested by offering subjects (N = 621) a series of choices between immediate rewards and larger, delayed rewards. In contrast to previous studies, in which hypothetical rewards have typically been employed, subjects in the present study were entered into a lottery in which they had a chance of actually receiving one of their choices. The delayed rewards were grouped into small ($30-$35), medium ($55-$65), and large amounts ($70-$85). Using a novel parameter estimation procedure, we estimated discounting rates for all three reward sizes for each subject on the basis of his/her pattern of choices. The data indicated that the discounting rate is a decreasing function of the size of the delayed reward (p < .0001), whether hyperbolic or exponential discounting functions are assumed. In addition, a reliable gender difference was found (p = .005), with males discounting at higher rates than females, on average. PMID- 24214811 TI - From a passing thought to a false memory in 2 minutes: Confusing real and illusory events. AB - The frequency with which subjects erroneously included a nonpresented word in their recall of a study list was explored in two experiments. The intrusion error was recalled by as many as 80% of the subjects, and when it was perceived to have been presented early in the study list, it was assigned confidence ratings and phenomenological retrieval characteristics equivalent to those for presented words. As a result, subjects were often unable to discriminate memories of real study words from their memories of a related but nonpresented word. Manipulations of encoding, but not of retrieval, conditions altered both the frequencies of illusory memories and their metamemorial characteristics. The results and paradigm are discussed in terms of their relevance to the "memory-recovery" debate. PMID- 24214812 TI - Implications of aging, lexicality, and item length for the mechanisms underlying memory span. AB - Hulme, Maughan, and Brown (1991) provided evidence that the contribution of long term memory to memory span performance was additive to the contribution of rehearsal rate (e.g., Baddeley, 1986). The present study further explored the relationship between these two contributions in younger and older adults. Speech rates and spans for short, medium, and long words and nonwords were obtained from subjects. Older adults had slower speech rates and smaller spans than did younger adults. Both groups' data were fit well by linear functions relating speech rates to spans. However, the slope of the function that relates speech rate to memory span was greater for words than for nonwords. This finding supports the idea that long-term memory, as well as rehearsal rate, contributes to span performance, and that this contribution is not simply additive. PMID- 24214813 TI - [Happy birthday, anaesthesia!]. PMID- 24214814 TI - Performance evaluation of stationary and semi-stationary acquisition with a non stationary small animal multi-pinhole SPECT system. AB - PURPOSE: Step-and-shoot mode with many angular steps results in long frame duration limiting the capability of single-photon emission computed tomography (SPECT) for fast dynamic scans. The present study evaluates acquisition with reduced angular sampling for fast imaging in preclinical research with the nanoSPECT/CTplus four-head multi-pinhole system. PROCEDURES: Measurements with line sources, homogeneity phantoms and a Jaszczak phantom filled with (99m)Tc or (123)I were performed to evaluate the 'stationary' and 'semi-stationary' acquisition mode (one or two detector positions, respectively) with respect to spatial resolution, quantification, noise properties and image artefacts. An in vivo mouse study was performed with (99m)Tc-MAG3. RESULTS: The fast acquisition modes resulted in only minor degradation of spatial resolution and quantification accuracy. Statistical noise in reconstructed images was significantly reduced compared to conventional SPECT, particularly at low count statistics. Stationary acquisition resulted in streak artefacts and spatial distortion. CONCLUSIONS: The semi-stationary acquisition mode of the nanoSPECT/CTplus allows fast dynamic SPECT with tolerable loss of image quality. PMID- 24214815 TI - Cancer prevention and control: where are the kids? PMID- 24214816 TI - Short and sweet: a short course on concise medical writing. PMID- 24214818 TI - High-frequency vibrational density of states of a disordered solid. AB - We investigate the high-frequency behavior of the density of vibrational states in three-dimensional elasticity theory with spatially fluctuating elastic moduli. At frequencies well above the mobility edge, instanton solutions yield an exponentially decaying density of states. The instanton solutions describe excitations, which become localized due to the disorder-induced fluctuations, which lower the sound velocity in a finite region compared to its average value. The exponentially decaying density of states (known in electronic systems as the Lifshitz tail) is governed by the statistics of a fluctuating-elasticity landscape, capable of trapping the vibrational excitations. PMID- 24214817 TI - Reducing smoking in pregnancy among Maori women: "aunties" perceptions and willingness to help. AB - Maori (the indigenous people of New Zealand) women have high rates of smoking during pregnancy and 42 % register with a lead maternity carer (LMC) after their first trimester, delaying receipt of cessation support. We used a participatory approach with Maori community health workers ("Aunties") to determine their willingness and perceived ability to find pregnant Maori smokers early in pregnancy and to provide cessation support. Three meetings were held in three different regions in New Zealand. The aunties believed they could find pregnant women in first trimester who were still smoking by using their networks, the 'kumara-vine' (sweet potato vine), tohu (signs/omens), their instinct and by looking for women in the age range most likely to get pregnant. The aunties were willing to provide cessation and other support but they said they would do it in a "Maori way" which depended on formed relationships and recognised roles within families. The aunties' believed that their own past experiences with pregnancy and/or smoking would be advantageous when providing support. Aunties' knowledge about existing proven cessation methods and services and knowledge about how to register with a LMC ranged from knowing very little to having years of experience working in the field. They were all supportive of receiving up-to-date information on how best to support pregnant women to stop smoking. Aunties in communities believe that they could find pregnant women who smoke and they are willing to help deliver cessation support. Our ongoing research will test the effectiveness of such an approach. PMID- 24214819 TI - Incorporating natural enemy units into a dynamic action threshold for the soybean aphid, Aphis glycines (Homoptera: Aphididae). AB - BACKGROUND: Recommended action thresholds for soybean aphid, Aphis glycines, do not adjust for natural enemy impact, although natural enemies contribute important biological control services. Because individual natural enemy species have varied impacts on pest population dynamics, incorporating the impact of a diverse predator guild into an action threshold can be cumbersome. RESULTS: Field surveys identified an aphidophagous natural enemy complex dominated by Orius insidiosus, Coccinella septempunctata, Harmonia axyridis and Aphelinus certus. Functional responses of O. insidiosus were determined in the laboratory, while predation rates of all other natural enemies were obtained from the literature. Natural enemy impacts were normalized using natural enemy units (NEUs), where 1 NEU = 100 aphids consumed or parasitized. A dynamic action threshold (DAT) was developed by combining NEUs with an A. glycines population growth model. With the DAT, an insecticide application was only triggered if natural enemy numbers were insufficient to suppress pest populations. In field experiments, DAT provided equivalent yields to the conventional action threshold and reduced the average number of pesticide applications. CONCLUSION: The DAT approach has the potential to reduce pesticide use, will help preserve natural enemy populations and can be applied to other pest systems with diverse natural enemy guilds. PMID- 24214820 TI - Current controversies in prenatal diagnosis 2: should incidental findings arising from prenatal testing always be reported to patients? PMID- 24214822 TI - The changing demographics of knee dislocation: a retrospective database review. AB - BACKGROUND: Knee dislocations are uncommon but devastating orthopaedic injuries. Little is known about their frequency and the types of patients who are affected. QUESTIONS/PURPOSES: Using a large national insurance database, we determined (1) the incidence of knee dislocation in patients with orthopaedic injuries and examined the incidence as a function of (2) year of diagnosis, (3) dislocation type (open versus closed, direction), and (4) patient demographic factors (sex, age). METHODS: We searched the PearlDiver database, a national database of private insurance records consisting of 11 million patients with orthopaedic diagnoses, using diagnosis (ICD-9-CM) codes for knee dislocation between the years 2004 and 2009. The PearlDiver database does not include Medicare, Medicaid, or uninsured patients. Patients were stratified by age, sex, and year of diagnosis. Incidence was defined as the number of dislocation events per 100 patient-years. RESULTS: We identified 8050 dislocations, representing an incidence of 0.072 events per 100 patient-years between 2004 and 2009. Annual dislocation incidence did not increase during the 6-year study period. Of the 8050 dislocations, 1333 (17%) were open and 6717 (83%) were closed, representing an incidence of 0.060 per 100 for closed dislocations and 0.012 per 100 for open dislocations. The most common direction of dislocation was unspecified or other (65%), followed by anterior (13%), lateral (11%), posterior (6%), and medial (5%). Of the patients sustaining dislocations, 4172 (52%) were female and 3878 (48%) were male. Males displayed an increased risk of knee dislocation compared to females (odds ratio = 1.09). The mean patient age was 35 years, and patient age was inversely correlated to the incidence of knee dislocation (10-year odds ratio = 0.77). CONCLUSIONS: Our data suggest that knee dislocation might represent a significantly larger burden among orthopaedic injuries than previously thought. The finding that males and females have a nearly equal risk of knee dislocation enhances the diagnosing physician's clinical suspicion of this injury. Future large prospective studies analyzing the various causes of knee dislocation could provide insight into the changing demographics of this injury. LEVEL OF EVIDENCE: Level IV, prognostic study. See Instructions for Authors for a complete description of levels of evidence. PMID- 24214823 TI - Surgical treatment of trapeziometacarpal joint arthritis: a historical perspective. AB - BACKGROUND: The trapeziometacarpal (TMC) joint's unique anatomy and biomechanics render it susceptible to degeneration. For 60 years, treatment of the painful joint has been surgical when nonoperative modalities have failed. Dozens of different operations have been proposed, including total or subtotal resection of the trapezium or resection and implant arthroplasty. Proponents initially report high levels of patient satisfaction, but longer-term reports sometimes fail to support initial good results. To date, no one procedure has been shown to be superior to another. QUESTIONS/PURPOSES: This review sought to identify factors responsible for the development of many different procedures to treat the same pathology and factors influencing whether procedures remain in the armamentarium or are abandoned. METHODS: I performed a nonsystematic historical review of English-language surgical journals using the key words "carpometacarpal arthritis", or "trapeziometacarpal arthritis", and "surgery" in combination with "history" using the PubMed database. In addition, bibliographies of pertinent articles were reviewed. RESULTS: The factors that led to many surgical innovations appear to be primarily theoretical concerns about the shortcomings of previously described procedures, especially about proximal migration of the thumb metacarpal after trapezial resection. Longevity of a particular procedure seems to be related to simplicity of design, especially for prosthetic arthroplasty. The evolution of surgery for TMC joint arthritis both parallels and diverges from that in other joints. For example, for most degenerated joints (even many in the hand), treatment evolved from resection arthroplasty to implant arthroplasty. In contrast, for the TMC joint, the 60-year-old procedure of trapezial resection continues to be performed by a majority of surgeons; many modifications of that procedure have been offered, but none have shown better pain reduction or increased function over the original procedure. In parallel, many differently designed prosthetic total or hemijoint arthroplasties have been proposed and performed, again with as yet unconvincing evidence that this technology improves results over those obtained by simple resection arthroplasty. CONCLUSIONS: Many procedures have been described to treat TMC joint arthritis, from simple trapezial resection to complex soft tissue arthroplasty to prosthetic arthroplasty. In the absence of evidence for the superiority of any one procedure, surgeons should consider using established procedures rather than adopting novel ones, though novel procedures can and should be tested in properly designed clinical trials. Tissue-engineered solutions are an important area of current research but have not yet reached the clinical trial stage. PMID- 24214824 TI - Classifications in brief: Letournel classification for acetabular fractures. PMID- 24214825 TI - Binding of mazindol and analogs to the human serotonin and dopamine transporters. AB - Mazindol has been explored as a possible agent in cocaine addiction pharmacotherapy. The tetracyclic compound inhibits both the dopamine transporter and the serotonin transporter, and simple chemical modifications considerably alter target selectivity. Mazindol, therefore, is an attractive scaffold for both understanding the molecular determinants of serotonin/dopamine transporter selectivity and for the development of novel drug abuse treatments. Using molecular modeling and pharmacologic profiling of rationally chosen serotonin and dopamine transporter mutants with respect to a series of mazindol analogs has allowed us to determine the orientation of mazindol within the central binding site. We find that mazindol binds in the central substrate binding site, and that the transporter selectivity can be modulated through mutations of a few residues in the binding pocket. Mazindol is most likely to bind as the R-enantiomer. Tyrosines 95 and 175 in the human serotonin transporter and the corresponding phenylalanines 75 and 155 in the human dopamine transporter are the primary determinants of mazindol selectivity. Manipulating the interaction of substituents on the 7-position with the human serotonin transporter Tyr175 versus dopamine transporter Phe155 is found to be a strong tool in tuning the selectivity of mazindol analogs and may be used in future drug design of cocaine abuse pharmacotherapies. PMID- 24214826 TI - Cross-modulation and molecular interaction at the Cav3.3 protein between the endogenous lipids and the T-type calcium channel antagonist TTA-A2. AB - T-type calcium channels (T/Ca(v)3-channels) are implicated in various physiologic and pathophysiologic processes such as epilepsy, sleep disorders, hypertension, and cancer. T-channels are the target of endogenous signaling lipids including the endocannabinoid anandamide, the omega3-fatty acids, and the lipoamino-acids. However, the precise molecular mechanism by which these molecules inhibit T current is unknown. In this study, we provided a detailed electrophysiologic and pharmacologic analysis indicating that the effects of the major N-acyl derivatives on the Ca(v)3.3 current share many similarities with those of TTA-A2 [(R)-2-(4-cyclopropylphenyl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2 yl)ethyl)acetamide], a synthetic T-channel inhibitor. Using radioactive binding assays with the TTA-A2 derivative [(3)H]TTA-A1 [(R)-2-(4-(tert-butyl)phenyl)-N-(1 (5-methoxypyridin-2-yl)ethyl)acetamide], we demonstrated that polyunsaturated lipids, which inhibit the Ca(v)3.3 current, as NAGly (N-arachidonoyl glycine), NASer (N-arachidonoyl-l-serine), anandamide, NADA (N-arachidonoyl dopamine), NATau (N-arachidonoyl taurine), and NA-5HT (N-arachidonoyl serotonin), all displaced [(3)H]TTA-A1 binding to membranes prepared from cells expressing Ca(v)3.3, with Ki in a micromolar or submicromolar range. In contrast, lipids with a saturated alkyl chain, as N-arachidoyl glycine and N-arachidoyl ethanolamine, which did not inhibit the Ca(v)3.3 current, had no effect on [(3)H]TTA-A1 binding. Accordingly, bio-active lipids occluded TTA-A2 effect on Ca(v)3.3 current. In addition, TTA-Q4 [(S)-4-(6-chloro-4-cyclopropyl-3-(2,2 difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl)benzonitrile], a positive allosteric modulator of [(3)H]TTA-A1 binding and TTA-A2 functional inhibition, acted in a synergistic manner to increase lipid-induced inhibition of the Ca(v)3.3 current. Overall, our results demonstrate a common molecular mechanism for the synthetic T-channel inhibitors and the endogenous lipids, and indicate that TTA-A2 and TTA-Q4 could be important pharmacologic tools to dissect the involvement of T-current in the physiologic effects of endogenous lipids. PMID- 24214827 TI - Response stratification and survival analysis of hepatocellular carcinoma patients treated with intra-arterial therapy using MR imaging-based arterial enhancement fraction. AB - PURPOSE: To investigate the feasibility that arterial enhancement fraction (AEF) is associated with response of hepatocellular carcinoma (HCC) following intra arterial therapy (IAT) and to compare AEF response with currently used tumor response metrics. MATERIALS AND METHODS: The AEF, Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) of the largest treated index lesion and AEF of the tumor-free hepatic parenchyma was measured on representative axial images in 131 patients (108 male; mean age, 61.9 years). Clinical measures and patient survival were assessed. Statistical analysis included Wilcoxon signed-rank test and the COX proportional hazards model. RESULTS: After IAT, the mean AEF of the tumor decreased by 22% (66.7-44.8%, P < 0.0001), while the mean AEF of the tumor-free parenchyma remained unchanged (27.2-26.5%, P = 0.50). Median survival of all 131 patients with liver cancer was 17 months. Patients were stratified into AEF responders if they had an AEF-decrease >=35% (AEF-responders: n = 67; AEF nonresponders: n = 64). AEF-responders survived longer than nonresponders (34.8 months versus 10.8 months, hazard ratio = 0.39; P < 0.0001). Responders according to RECIST, mRECIST, or EASL did not survive significantly longer compared with nonresponders. CONCLUSION: Evaluating the AEF values based on tri-phasic MRI is associated with tumor response in patients with unresectable HCC treated with IAT. PMID- 24214828 TI - Written-in conductive patterns on robust graphene oxide biopaper by electrochemical microstamping. AB - The silk road: By employing silk fibroin as a binder between graphene oxide films and aluminum foil for a facile, highly localized reduction process, conductive paper is reinvented. The flexible, robust biographene papers have high toughness and electrical conductivity. This electrochemical written-in approach is readily applicable for the fabrication of conductive patterned papers with complex circuitries. PMID- 24214829 TI - The cross-dehydrogenative coupling of C(sp3)-H bonds: a versatile strategy for C C bond formations. AB - Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of C?C bonds by directly connecting two different C?H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C?H bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative C sp 3?C formations and provides a comprehensive overview on existing procedures and employed methodologies. PMID- 24214830 TI - Tensile properties of a morphologically split supraspinatus tendon. AB - The supraspinatus tendon consists morphologically of two sub-regions, anterior and posterior. The anterior sub-region is thick and tubular while the posterior is thin and strap-like. The purpose of this study was to compare the structural and mechanical properties of the anterior and posterior sub-regions of the supraspinatus tendon. The supraspinatus tendons from seven human cadaveric shoulders were morphologically divided into the anterior and posterior sub regions. Length, width, and thickness were measured. A servo-hydraulic testing machine (MTS Systems Corporation, Minneapolis, MN) was used for tensile testing. The maximal load at failure, modulus of elasticity and ultimate tendon stress were calculated. Repeated measures were used for statistical comparisons. The mean anterior tendon cross-sectional area was 47.3 mm(2) and the posterior was 32.1 mm(2) . Failure occurred most often at the insertion site: anterior (5/7) and posterior (6/7). All parameters of the anterior sub-region were significantly greater than those of the posterior sub-region. The moduli of elasticity at the insertion site were 592.4 MPa in the anterior sub-region and 217.7 MPa in the posterior (P = 0.01). The ultimate failure loads were 779.2 N in the anterior sub region and 335.6 N in the posterior (P = 0.003). The ultimate stresses were 22.1 MPa in the anterior sub-region and 11.6 MPa in the posterior (P = 0.008). We recognized that the anterior and posterior sub-regions of the SSP tendon have significantly different mechanical properties. In a future study, we need to evaluate how best to repair an SSP tendon considering these region-specific properties. PMID- 24214831 TI - Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer Ca Ski cells. AB - Flavonoids have antitumoral properties and may be attractive candidates as anticancer therapy. Isoliquiritigenin which is a constituent of licorice (Glycyrrhiza inflata), a plant commonly used in traditional Uyghur medicine in Xinjiang, China, was studied for antiproliferative and apoptotic activity in human cervical cancer cells, Ca Ski, SiHa, HeLa, and C-33A. Its molecular mechanism of action was specifically examined in Ca Ski cells. Isoliquiritigenin decreased cell viability, induced cell accumulation in G2/M and morphological and biochemical features of apoptosis in the four cancer cell lines. In Ca Ski cells, isoliquiritigenin led to a downregulation of HPV16 E6 expression associated with an increase of p53 and p21 levels, enhanced expression of Bax and decreased expression of Bcl-2 and Bid proform triggering dissipation of the mitochondrial membrane potential, released cytochrome c to the cytosol followed by activation of caspase cascade with cleavage of caspase-9, caspase-3, and PARP. Caspase-8 was also cleaved. Moreover treatment with a pan-caspase inhibitor prevented apoptosis. As Ca Ski cells are representative of carcinoma naturally occurring in the cervix, our results suggest a potential benefit of isoliquiritigenin for cervical cancer prevention and treatment. PMID- 24214832 TI - Cyanidin-3-O-sambubioside from Acanthopanax sessiliflorus fruit inhibits metastasis by downregulating MMP-9 in breast cancer cells MDA-MB-231. AB - Anthocyanins play an important role in physiological functions related to human health. This study aimed to investigate the inhibitory effect of cyanidin-3-O sambubioside isolated from Acanthopanax sessiliflorus fruit on cancer cell metastasis. The inhibitory effect of cyanidin-3-O-sambubioside on angiogenesis was assessed by chorioallantoic membrane and tube formation assays. Cyanidin-3-O sambubioside interrupted the formation of neovasculature and tube-like structures in a dose-dependent manner. It inhibited the wound healing migration and invasion of MDA-MB-231 cells through reconstituted extracellular matrix (Matrigel). Gelatin zymography revealed that cyanidin-3-O-sambubioside significantly decreased the secretion of matrix metalloproteinase-9 and inhibited matrix metalloproteinase-9 expression. In additional, cyanidin-3-O-sambubioside exerted an inhibitory effect on Akt phosphorylation. These results suggest that cyanidin 3-O-sambubioside inhibits metastasis processes, such as angiogenesis and invasion, in breast cancer cells through regulation of matrix metalloproteinase-9 activity. PMID- 24214833 TI - Differences in pharmacokinetics and anti-inflammatory effects between decoction and maceration of Sanhuang Xiexin Tang in rats and mice. AB - The pharmacokinetics and anti-inflammatory effects of Sanhuang Xiexin Tang, composed of Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, prepared by decoction and maceration, were investigated and compared. Rats were orally administered with the decoction and maceration of Sanhuang Xiexin Tang at 30 g/kg. The concentrations of 10 active constituents (berberine, palmatine, jatrorrhizine, coptisine, wogonin, baicalin, wogonoside, emodin, aloe-emodin, and rhein) in plasma were determined by UPLC-MS/MS. Mice were orally administered decoctions and macerations of Sanhuang Xiexin Tang continuously for 7 days at three doses and stimulated with lipopolysaccharide. The plasma concentrations of IL-10 and TNF-alpha were determined by ELISA. Different preparation methods resulted in significant differences in the pharmacokinetic characteristics of the SXT constituents, especially the protoberberine alkaloids. Maceration decreased the absorption of flavones while promoting the absorption of anthraquinones. Bioavailability of both flavones and anthraquinones increased after administration of macerated Sanhuang Xiexin Tang, especially those of baicalin and rhein, which increased by 3.27 and 7.10 times. Results of ELISA indicated that both the decoction and maceration of Sanhuang Xiexin Tang could significantly increase IL-10 production (p < 0.01) as well as decrease TNF-alpha production (p < 0.01). Macerated Sanhuang Xiexin Tang has a slightly higher anti inflammatory effect than the Sanhuang Xiexin Tang decoction. Different preparation methods affected the pharmacokinetic characteristics and anti inflammatory effects of Sanhuang Xiexin Tang's active constituents. PMID- 24214834 TI - Effects of praeruptorin A and praeruptorin C, a racemate isolated from Peucedanum praeruptorum, on MRP2 through the CAR pathway. AB - Praeruptorin A and praeruptorin C, racemic to each other, are main bioactive constituents of the species Peucedanum praeruptorum, traditionally used as a Chinese herbal medicine (also known as Bai-Hua Qian Hu). In the present study, the ability of praeruptorins A and C to activate the constitutive androstane receptor and induce human multidrug resistance-associated protein 2 expressions in HepG2 cells was investigated. The changes in mRNA level, protein expression, and transport activity of multidrug resistance-associated protein 2 were determined by quantitative real-time PCR, Western blot, and the CDF uptake assay, respectively. The effects of constitutive androstane receptor knockdown on multidrug resistance-associated protein 2 mRNA and protein expression were also measured by transient transfection of a specific constitutive androstane receptor siRNA. The results showed that praeruptorin A and praeruptorin C significantly induced the multidrug resistance-associated protein 2 mRNA and protein expression, and enhanced the transport activity of multidrug resistance associated protein 2. A further study showed that mRNA and protein upregulation were attenuated by transient transfection of a specific constitutive androstane receptor siRNA, suggesting that the upregulation of multidrug resistance associated protein 2 was mediated by the constitutive androstane receptor. Taken together, our findings indicate that praeruptorin A and praeruptorin C can significantly upregulate multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction. PMID- 24214835 TI - Topical application of St. John's wort (Hypericum perforatum). AB - St. John's wort (Hypericum perforatum) has been intensively investigated for its antidepressive activity, but dermatological applications also have a long tradition. Topical St. John's wort preparations such as oils or tinctures are used for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, myalgia, and many others. Pharmacological research supports the use in these fields. Of the constituents, naphthodianthrones (e.g., hypericin) and phloroglucinols (e.g., hyperforin) have interesting pharmacological profiles, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. In addition, hyperforin stimulates growth and differentiation of keratinocytes, and hypericin is a photosensitizer which can be used for selective treatment of nonmelanoma skin cancer. However, clinical research in this field is still scarce. Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex infections, partly with purified single constituents and modern dermatological formulations. St. John's wort also has a potential for use in medical skin care. Composition and stability of pharmaceutical formulations vary greatly depending on origin of the plant material, production method, lipophilicity of solvents, and storage conditions, and this must be regarded with respect to practical as well as scientific purposes. PMID- 24214836 TI - Daphniphyllum alkaloids: recent findings on chemistry and pharmacology. AB - The unique polycyclic fused ring systems of Daphniphyllum alkaloids, along with their extensive bioactivities, make this family of alkaloids especially attractive targets for total synthesis and biogenetic studies. Successive discoveries of new alkaloids with unprecedented skeletons have made a great contribution to structural diversities of alkaloids elaborated by plants of the genus Daphniphyllum. By the end of 2008, more than 200 alkaloids belonging to 14 different skeletal types have been isolated from different parts of plants of thirteen Daphniphyllum species. These alkaloids show cytotoxic, antioxidant, vasorelaxant, and antiplatelet activating factor effects. The plausible biosynthetic pathways for Daphniphyllum alkaloids have been proposed and biomimetic total syntheses of some alkaloids completed. To provide an update of the previous reviews published in 2009, new structures, synthesis, and bioactivity of Daphniphyllum alkaloids reported in recent years are presented in this article. In the meantime, an additional 54 novel alkaloids have been isolated and identified. Among them, some possess unprecedented frameworks. Several inspired organic syntheses were completed. PMID- 24214837 TI - Effects of bacteriophage on the quality and shelf life of Paralichthys olivaceus during chilled storage. AB - BACKGROUND: The microbiological spoilage of fishery foods is mainly due to specific spoilage organisms (SSOs), with Shewanella putrefaciens being the SSO of most chilled marine fish. Bacteriophages have shown excellent capability to control micro-organisms. The aim of this study was to determine a specific bacteriophage to prevent spoilage by reducing SSO (S. putrefaciens) levels in the marine fish Paralichthys olivaceus (olive flounder) under chilled storage. RESULTS: Chilled flounder fillets were inoculated with S. putrefaciens and treated with different concentrations of bacteriophage Spp001 ranging from 10(4) to 10(8) plaque-forming units (pfu) mL(-1) . Bacterial growth (including total viable count and SSO) of the bacteriophage-treated groups was significantly inhibited compared with that of the negative control group (P < 0.05). Sensory evaluation and biochemical parameters revealed that the bacteriophage could extend the shelf life of chilled flounder fillets (from <4 to 14 days) with good esthetic quality, even at low temperature (4 degrees C). Furthermore, bacteriophage concentrations of 10(6) and 10(8) pfu mL(-1) were more effective than the chemical preservative potassium sorbate (5 g L(-1) ). CONCLUSION: The bacteriophage Spp001 offered effective biocontrol of S. putrefaciens under chilled conditions, retaining the quality characteristics of spiked fish fillets, and thus could be a potential candidate for use in chilled fish fillet biopreservation. PMID- 24214838 TI - Update in hospital palliative care. AB - BACKGROUND: Seriously ill patients frequently receive care in hospitals, and palliative care is a core competency for hospitalists. We aimed to summarize and critique recent research that has the potential to impact the clinical practice of palliative care in the hospital. METHODS: We reviewed articles published between January 2012 and May 2013, identified through a hand-search of leading journals and PubMed. The authors collectively selected 9 articles based on their scientific rigor and relevance to hospital practice. We review their findings, strengths, and limitations and make recommendations for practice. RESULTS: Key findings include: indwelling pleural catheters and talc pleurodesis provide similar relief of dyspnea in patients with malignant pleural effusions; oxygen many not be needed to prevent dyspnea in many dying patients; docusate may not be needed in addition to sennosides to treat opioid-induced constipation; atropine is no more effective than placebo in treating respiratory rattles in dying patients; many older adult survivors of in-hospital cardiopulmonary resuscitation (CPR) are alive up to 1 year after discharge; observing CPR may decrease family post-traumatic stress; surrogates of intensive care unit patients often interpret prognostic information optimistically; many patients with metastatic cancer feel that chemotherapy may cure their disease; viewing a goals-of-care video may decrease preference for CPR in patients being admitted to skilled nursing facilities. CONCLUSIONS: Recent research provides important insights into the effectiveness of medications and interventions for symptom management, outcomes of CPR for patients and families, and Journal of Hospital Medicine 2013;8:715 720. (c) 2013 Society of Hospital Medicine. PMID- 24214839 TI - Augmenting aquatic species sensitivity distributions with interspecies toxicity estimation models. AB - Species sensitivity distributions (SSDs) are cumulative distribution functions of species toxicity values. The SSD approach is being used increasingly in ecological risk assessment but is often limited by available toxicity data needed for diverse species representation. In the present study, the authors evaluate augmenting aquatic species databases limited to standard test species using toxicity values extrapolated from interspecies correlation estimation (ICE) models for SSD development. The authors compared hazard concentrations at the 5th centile (HC5) of SSDs developed using limited measured data augmented with ICE toxicity values (augmented SSDs) with those estimated using larger measured toxicity datasets of diverse species (reference SSDs). When SSDs had similar species composition to the reference SSDs, 0.76 of the HC5 estimates were closer to the reference HC5; however, the proportion of augmented HC5s that were within 5-fold of the reference HC5s was 0.94, compared with 0.96 when predicted SSDs had random species assemblages. The range of toxicity values among represented species in all SSDs also depended on a chemical's mode of action. Predicted HC5 estimations for acetylcholinesterase inhibitors showed the greatest discrepancies from the reference HC5 when SSDs were limited to commonly tested species. The results of the present study indicate that ICE models used to augment datasets for SSDs do not greatly affect HC5 uncertainty. Uncertainty analysis of risk assessments using SSD hazard concentrations should address species composition, especially for chemicals with known taxa-specific differences in toxicological effects. This article is a US Government work and is in the public domain in the USA. PMID- 24214840 TI - Promoting gynecologic cancer awareness at a critical juncture--where women and providers meet. AB - Given the absence of effective population-based screening tests for ovarian, uterine, vaginal, and vulvar cancers, early detection can depend on women and health care providers recognizing the potential significance of symptoms. In 2008, the Centers for Disease Control and Prevention's (CDC) Inside Knowledge campaign began distributing consumer education materials promoting awareness of gynecologic cancer symptoms. We investigated providers' in-office use of CDC gynecologic cancer materials and their recognition of the symptoms highlighted in the materials. We analyzed data from a national 2012 survey of US primary care physicians, nurse practitioners, and gynecologists (N = 1,380). Less than a quarter of providers (19.4%) reported using CDC gynecologic cancer education materials in their offices. The provider characteristics associated with the use of CDC materials were not consistent across specialties. However, recognition of symptoms associated with gynecologic cancers was consistently higher among providers who reported using CDC materials. The possibility that providers were educated about gynecologic cancer symptoms through the dissemination of materials intended for their patients is intriguing and warrants further investigation. Distributing consumer education materials in health care provider offices remains a priority for the Inside Knowledge campaign, as the setting where women and health care providers interact is one of the most crucial venues to promote awareness of gynecologic cancer symptoms. PMID- 24214841 TI - Structure elucidation of ACE-inhibitory and antithrombotic peptides isolated from mackerel skin gelatine hydrolysates. AB - BACKGROUND: The fish-processing industry generates significant amounts of waste and by-products that are usually discarded. This study investigated the preparation of bioactive gelatine peptides from fish skin. Gelatine was extracted from mackerel (Scomber scombrus) skin and hydrolysed by pepsin for 1, 2, 6 and 24 h. All hydrolysates were screened for antioxidant, ACE-inhibitory and antithrombotic activities. RESULTS: Gelatine peptides obtained after 24 h of hydrolysis exhibited the highest antioxidant activity (DPPH reduction ~80%, FRAP ~130 umol Trolox equivalent L(-1) ). These hydrolysates had high ACE-inhibitory activity (>70%) and were able to significantly (P < 0.05) inhibit platelet aggregation by about 30%, corresponding to moderate antithrombotic activity. CONCLUSION: The bioactive properties were mainly due to the presence of low molecular-weight peptides of 337 and 423 Da. PMID- 24214842 TI - Morphological analysis of the branches of the dorsal pancreatic artery and their clinical significance. AB - The dorsal pancreatic artery (DP), characterized by a course that crosses behind the proximal part of the splenic vein. It is regarded as clinically important, providing essential distribution to the pancreas. However, the origin of the DP is extremely variable and therefore cannot provide a sufficient basis for identifying it. The DPs of 11 cadavers were investigated in terms of origin, course and distribution. A total of 45 branches of the DP are classified into seven types on the basis of course and distribution. One of these seven types was consistently observed among the specimens: it ran to the right, passed behind the superior mesenteric vein and anterior surface of the posterior part of the head of the pancreas, and then distributed to the uncinate process and the posterior part of the head of the pancreas. Variations in the branching pattern of the DP can be explained from the following perspective: the consistent branch (#5) is the stem of the DP, and other branches originate from it. It is advisable for surgeons to pay attention to this consistent branch of the dorsal pancreatic artery when performing a pancreaticoduodenectomy. PMID- 24214843 TI - Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet. AB - SCOPE: Genistein (GEN) is a compound that has been shown to alleviate hepatic steatosis. Here, we investigated its protective effects against non-alcoholic steatohepatitis (NASH) development in apolipoprotein E-deficient (ApoE(-/-) ) mice fed a high-fat diet (HFD). METHODS AND RESULTS: Wild-type and ApoE(-/-) mice were fed an HFD with or without GEN (0.5 g/kg diet) for 24 weeks. Body weights were reduced and fecal cholesterol excretion was increased by GEN. GEN supplementation lowered serum and hepatic cholesterol and lipid peroxidation levels, and hepatic heme oxygenase 1 protein levels in ApoE(-/-) mice. Hepatic expressions of scavenger receptors involved in oxidized LDL uptake, CD36 and scavenger receptor A, were downregulated by GEN. GEN reduced serum alanine aminotransferase and monocyte chemoattractant protein 1 levels, and hepatic nuclear factor-kappaB-mediated inflammatory gene expressions in ApoE(-/-) mice. These levels were higher in ApoE(-/-) mice fed an HFD than their corresponding wild-type mice. GEN also alleviated hepatic steatosis by reducing mRNA levels of monoacylglycerol O-acyltransferase 1, a target gene of peroxisome proliferator activated receptor gamma. CONCLUSION: GEN alleviated NASH as well as hypercholesterolemia and obesity in ApoE(-/-) mice fed an HFD. Restoration of altered cholesterol metabolism and oxidative stress may be involved in the protective effect of GEN against NASH development. PMID- 24214844 TI - Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow. AB - PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and negative healthy individuals using cine phase contrast imaging. MATERIALS AND METHODS: Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled >=2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes. RESULTS: CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021). CONCLUSION: CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals. PMID- 24214846 TI - First-principles study of the BiMO4 antisite defect in the Bi12MO20 (M=Si, Ge, Ti) sillenite compounds. AB - Structural, electronic and optical properties of the antisite BiMO4 defect in Bi12MO20 sillenites (BMO, M=Si, Ge, Ti) were investigated using density functional theory. The defect is studied in neutral, positively and negatively charged states. It is demonstrated that within the neutral defect the Bi 6s(2) lone pair is broken and the valence state of the Bi is 4+ (6s(1)). Within the charged defects, the Bi 6s orbital is found to be either full (Bi(3+): 6s(2)) or empty (Bi(5+): 6s(0)). All three charged states introduce energy bands within the BMO gap. By analyzing possible transitions between them we deduced a simple model of functioning of the BiMO4 defect that is able to explain the photochromic and photorefractive effect in sillenites and that reproduces almost all known experimental facts. PMID- 24214845 TI - Synthesis and applications of alpha-trifluoromethylated alkylboron compounds. AB - RBF3 K is a chemist's BFF: A metal-free synthetic route to unprecedented organoboron compounds bearing an alpha-trifluoromethyl substituent, employing a variety of trifluoroborate (RBF3 K) starting materials, is reported. These substrates represent the first isolated alpha-trifluoromethylated alkylboron building blocks, and these reagents lead to a variety of useful bench-stable, synthetic intermediates. Pin=pinacol. PMID- 24214847 TI - Comment on the association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation. PMID- 24214848 TI - Author's response to letter to the editor (JOR-13-0436) that refers to "Molecular mechanisms of cell sheet fragment in enhancing bone formation in mandibular distraction". PMID- 24214849 TI - Nickel cluster growth on defect sites of graphene: a computational study. PMID- 24214850 TI - DBD dyes as fluorescence lifetime probes to study conformational changes in proteins. AB - Previously, [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD)-based fluorophores used as highly sensitive fluorescence lifetime probes reporting on their microenvironmental polarity have been described. Now, a new generation of DBD dyes has been developed. Although they are still sensitive to polarity, in contrast to the former DBD dyes, they have extraordinary spectroscopic properties even in aqueous surroundings. They are characterized by long fluorescence lifetimes (10-20 ns), large Stokes shifts (~100 nm), high photostabilities, and high quantum yields (>0.56). Here, the spectroscopic properties and synthesis of functionalized derivatives for labeling biological targets are described. Furthermore, thio-reactive maleimido derivatives of both DBD generations show strong intramolecular fluorescence quenching. This mechanism has been investigated and is found to undergo a photoelectron transfer (PET) process. After reaction with a thiol group, this fluorescence quenching is prevented, indicating successful bonding. Being sensitive to their environmental polarity, these compounds have been used as powerful fluorescence lifetime probes for the investigation of conformational changes in the maltose ATP-binding cassette transporter through fluorescence lifetime spectroscopy. The differing tendencies of the fluorescence lifetime change for both DBD dye generations promote their combination as a powerful toolkit for studying microenvironments in proteins. PMID- 24214851 TI - Toxic compounds in honey. AB - There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food. PMID- 24214852 TI - Genetic assessment of common bean (Phaseolus vulgaris L.) accessions by peroxidase gene-based markers. AB - BACKGROUND: Peroxidase, a plant-specific oxidoreductase, is a heme-containing glycoprotein encoded by a large multigenic family in plants. Plant peroxidases (POXs, EC 1.11.1.7) play important roles in many self-defense interactions in plants. Here, 67 common bean (Phaseolus vulgaris L.) genotypes were studied using a POX gene-based marker method. Comparison of POX genes could resolve evolutionary relationships in common bean. RESULTS: Eighty fragments were obtained with 20 primer pairs that amplified one (POX8c) to eight (ATP29) bands, with a mean of four bands per primer pair. The average (polymorphic information content) PIC value for the POX products was 0.40. The maximum variation (93%) was found between Turkey (#33) and India (#52) and between Antalya (#33) and India (#53). The minimum variation (0%) was found among four pairs: Bozdag (#2) and Karadeniz (#38), Kirklareli (#11) and Turkey (#15, 16, 43), Bandirma (#13) and Turkey (#15, 16, 43), and Kirklareli (#10) and Bandirma (#22). UPGMA was used to discriminate the common bean genotypes into five clusters, while STRUCTURE software was used to investigate the genetic population structure. CONCLUSION: The results showed that POX gene family markers can be used to study genotypic diversity and provide new information for breeding programs and common bean improvement practices. PMID- 24214853 TI - Patient-centered perspectives on the access to educational opportunities specific to lifestyle modification in men at risk for primary or secondary prostate cancer. AB - Educating men at risk for primary or secondary prostate cancer on lifestyle modification may help prevent the development of the disease, reduce the risk of recurrence in those treated for cancer, and slow the progression of active disease. To date, substantial literature on male patient attitudes towards risk modification does not exist. In this project, we evaluate the attitudes and educational needs of men at high-risk for primary or secondary prostate cancer to assess the need for a dedicated clinic focused on education and prevention. Two clinic nurses administered surveys to 76 male patients seen at the University Kansas Cancer Center (KUCC) and Urology clinics. Survey responses showed the patients' perspectives and desire for more support and education regarding late effects of treatment, management of risk, and lifestyle modification. Findings from this survey inspired the establishment of the Burns & McDonnell High-Risk Prostate Cancer Prevention Program at KUCC. PMID- 24214854 TI - Comparison of anti-inflammatory potential of four different dibenzocyclooctadiene lignans in microglia; action via activation of PKA and Nrf-2 signaling and inhibition of MAPK/STAT/NF-kappaB pathways. AB - SCOPE: The aim of our study was to determine the signaling pathways associated with the antineuroinflammatory and neuroprotective responses induced by dibenzocyclooctadiene lignans in microglia. METHODS AND RESULTS: We employed ELISA, gelatin zymography, transient transfection, Western blot, chromatin immunoprecipitation, and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assays to characterize the effects of dibenzocyclooctadiene lignans on microglia. We found that dibenzocyclooctadiene lignans suppress TLR 2/4 agonist-induced pro-inflammatory cytokines and chemokines, PGE2 , nitric oxide, reactive oxygen species (ROS), and MMP-9 enzymatic activity through the suppression of MAPK, NF-kappaB, and JAK-STAT activation. We next demonstrated that dibenzocyclooctadiene lignans induced the expression of phase II detoxifying/antioxidant enzymes and suppressed the iNOS and ROS activation induced by TLR 2/4 agonists. Interestingly, we also found that dibenzocyclooctadiene lignans induced PKA/CREB/Nrf-2 activation in microglia and that activation of phase II detoxifying/antioxidant enzymes via stimulation of the PKA/CREB/Nrf-2 pathway attenuated TLR 2/4 agonist-induced iNOS and ROS activation. Furthermore, dibenzocyclooctadiene lignans protected primary cortical neurons against microglia-mediated neurotoxicity. CONCLUSION: Our findings indicate that phase II detoxifying/antioxidant enzymes and their upstream effectors, PKA/CREB/Nrf-2, play a pivotal role in the antineuroinflammatory and neuroprotective effects of dibenzocyclooctadiene lignans in TLR 2/4 agonist stimulated microglia. PMID- 24214855 TI - Nano-TiO(2) improve the photosynthesis of tomato leaves under mild heat stress. AB - Nano-TiO(2) has been reported to promote photosynthesis in some crops; however, the mechanism behind this action remains unknown. In this research, the effects of nano-TiO(2) on leaf photosynthesis under mild heat stress were investigated. Results showed that the net photosynthetic rate, conductance to H2O, and transpiration rate of tomato leaves increased after application of an appropriate concentration of nano-TiO(2). Nano-TiO(2) also significantly decreased the minimum chlorophyll fluorescence and relative electron transport in leaves. Under mild heat stress, Nano-TiO(2) increased regulated photosystem II (PS II) energy dissipation and decreased non-regulated PS II energy dissipation. These results indicate that nano-TiO(2) plays a positive role in promoting photosynthesis in tomato leaves under mild heat stress. PMID- 24214856 TI - Selenium attenuates high glucose-induced ROS/TLR-4 involved apoptosis of rat cardiomyocyte. AB - The potential mechanism of high glucose-induced cardiomyocyte apoptosis and selenium's protective effects were investigated in this study. Myocytes isolated from neonate rats were cultured in high-glucose medium (25.5 mmol/L glucose) to mimic sustained hyperglycemia. Before high-glucose incubation, myocytes were pretreated by sodium selenite solution. Cell apoptosis was evaluated by annexin V/propidium iodide (PI) staining and caspase activation. Expression of Toll-like receptor 4 (TLR-4) and myeloid differentiation factor 88 (MyD-88) was examined at both mRNA and protein levels. The intracellular reactive oxygen species (ROS) production and glutathione peroxidase (GPx) activity in myocytes were also detected. We found high glucose-induced cell apoptosis and activation of TLR 4/MyD-88/caspase-8/caspase-3 signaling, accompanied by increased production of ROS. Selenium pretreatment attenuated apoptosis in high glucose-incubated myocytes, and mechanically, this protective effect was found to be associated with attenuating oxidative status by increasing activity of GPx, decreasing the generation of ROS, as well as inhibition of the activation of TLR-4/MyD 88/caspase-8/caspase-3 signaling in myocytes. These results suggest that activation of TLR-4/MyD-88 signaling pathway plays an important role in high glucose-induced cardiomyocyte apoptosis. Additionally, by modulating TLR-4/MyD-88 signaling pathway, which is linked to ROS formation, selenium exerts its antioxidative and antiapoptotic effects in high glucose-incubated myocytes. PMID- 24214857 TI - The influence of growth conditions on strain differentiation within the Lactobacillus acidophilus group using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling. AB - RATIONALE: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling of bacteria is often used to distinguish isolates beyond the species level, even to the level of individual strains. However, the influence of bacterial growth conditions on the discriminatory power of the method to the strain level has not yet been properly evaluated. METHODS: For the purpose of this study, we used an extraction protocol recommended for clinical laboratories for MALDI-TOF MS profiling of bacteria. Seventeen closely related strains of the Lactobacillus acidophilus group were cultivated under various growth conditions (growth medium, time, and temperature) and analyzed. RESULTS: Out of a total of 327 samples, 80 % were correctly assigned to the species level and 13 % only to the genus level. When using data obtained from strains cultured for lengthy periods (7 days), the identification success rate was reduced due to poor signal quality, whereas with shorter cultivation times there was no influence of growth conditions on the assignment of particular strains to their corresponding species. However, variations in certain cultivation parameters were found to influence identification and differentiation of most of the examined strains. Strain discrimination was frequently found to be dependent on the selection of culture conditions. MALDI-TOF MS data treatment (strain-specific peak detection, BioTyper scoring, subtyping, or cluster analysis) also contributed to the discriminatory power of the method. CONCLUSIONS: When MALDI-TOF MS profiling of bacteria is used for strain discrimination, the cultivation conditions should be properly optimized and controlled as they significantly contribute to the discriminatory power of the method. PMID- 24214858 TI - A specific method of 34S labelling provides evidence that sulphate assimilation occurs in developing seeds and pod walls of Brassica napus L. subjected to ample or limited S nutrition. AB - RATIONALE: Seeds from different species actively assimilate sulphur (S) from sulphate. This has never been proved for Brassica napus L., a high S demanding plant, especially with regard to S limitation. The role of pod walls in the assimilation and allocation of S in well-fed and sulphate-limited conditions also needs to be clarified. METHODS: Freshly harvested seeds and pod walls from plants well-supplied (HS) or limited with sulphate (LS) from the 'visible buds' stage were subjected to a nutrient solution containing (34)S-sulphate (10 atom% excess) for 24 h. The (34)S labelling of the sulphate and protein fractions was determined with an elemental analyser connected to a continuous flow isotope ratio mass spectrometer. The amino acid profiles of seeds and pod walls were also determined by ion-exchange chromatography. RESULTS: The 24 h of (34)S-sulphate feeding treatment leads to an important production of proteins in HS and LS seeds, associated with a decrease in numerous amino acid contents. The treatment also leads to an incorporation of (34)S in seeds and pod walls proteins in both HS and LS conditions. The incorporation of (34)S in proteins was not different between HS and LS seeds, but was lower in LS than in HS pod walls, related to a higher incorporation in the other organic S compounds. CONCLUSIONS: This study provides evidence that Brassica napus seeds and pod walls are able to assimilate sulphate in HS and LS conditions, and that the LS condition leads to enhancement of the sulphate assimilation capacity of pod walls, which may be of crucial importance for the allocation of S to developing seeds. PMID- 24214859 TI - Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging. AB - RATIONALE: Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high-speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. METHODS: In this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections. RESULTS: The high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution. CONCLUSIONS: We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. PMID- 24214860 TI - Quantitative analysis of gamma- and delta-lactones in wines using gas chromatography with selective tandem mass spectrometric detection. AB - RATIONALE: Aroma relevant gamma- and delta-lactones are important flavor compounds in various foodstuffs. Their quantitative determination is essential for evaluating food sensory properties as well as food authenticity studies. METHODS: High-throughput head-space solid-phase microextraction as sample preparation, separation by capillary gas chromatography coupled with triple stage quadrupole mass spectrometry has been evaluated as the analytical method. RESULTS: Monitoring selected reaction mass fragments allowed sub-ug/L quantification of gamma- and delta-lactones in complex wine matrices. CONCLUSIONS: Tandem mass spectrometry improves specific detection of gamma- and delta-lactones, a prerequisite for reliable quantification at low-ug/L concentration levels in complex wine matrices. PMID- 24214861 TI - Alternating current corona discharge/atmospheric pressure chemical ionization for mass spectrometry. AB - RATIONALE: Although alternating current (ac) corona discharge has been widely used in the fields of material science and technology, no reports have been published on its application to an atmospheric pressure chemical ionization (APCI) ion source. In this work, ac corona discharge for an APCI ion source has been examined for the first time. METHODS: The ambient atmospheric pressure ac corona discharge (15 kHz, 2.6 kVptp ) was generated by using a stainless steel acupuncture needle. The generated ions were measured using an ion trap mass spectrometer. A comparative study on ac and direct current (dc) corona APCI ion sources was carried out using triacetone triperoxide and trinitrotoluene as test samples. RESULTS: The ac corona discharge gave ion signals as strong as dc corona discharge for both positive and negative ion modes. In addition, softer ionization was obtained with ac corona discharge than with dc corona discharge. The erosion of the needle tip induced by ac corona was less than that obtained with positive mode dc corona. CONCLUSIONS: A good 'yardstick' for assessing ac corona is that it can be used for both positive and negative ion modes without changing the polarity of the high-voltage power supply. Thus, ac corona can be an alternative to conventional dc corona for APCI ion sources. PMID- 24214862 TI - Combined phospho- and glycoproteome enrichment in nephrocalcinosis tissues of phytate-fed rats. AB - RATIONALE: Protein post-translational modifications (PTMs) are directly involved in protein function and cellular activities. Among them, glycosylation and phosphorylation are particularly important modifications on proteins located at extracellular and intracellular domains, respectively. However, the combined detection using phospho- and glycoproteomics is limited mainly due to protocol differences. METHODS: In this study, we developed a novel method for both phospho and glycoproteome detection from a single sample batch, in which a titanium dioxide cartridge was used to capture the phosphoproteome, and the flow-through solution was processed for capturing N-linked glycopeptides using hydrazide resin. RESULTS: By using 1 mg of protein from kidney tissue lysates from normal and diseased rats, we concurrently identified 437 glycosites/358 phosphosites and 468 glycosites/369 phosphosites in normal and disease kidneys, respectively, by liquid chromatography/tandem mass spectrometric analysis. CONCLUSIONS: Compared with individual PTM analyses, the combined PTM analysis clearly provides more broad implications for PTMs related to the pathological status and discovery of biomarker candidates. Furthermore, the combined protocol thoroughly showed its advantages in enrichment efficiency and biological interpretation compared with current methods. PMID- 24214863 TI - Quantitative analysis of polysorbates 20 and 40 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. AB - RATIONALE: Polysorbates are nonionic surfactants that consist primarily of fatty acid esters of polyethoxy sorbitan. This study proved that polysorbates can be quantitatively analyzed by matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS). Using MALDI-TOF MS, relative intensity and concentration ratios were correlated, and extensive research was conducted to understand the influencing factors. METHODS: Polysorbate 20 and 40 were mixed in the desired ratios and irradiated with a N2 laser. MALDI-TOF mass spectra were recorded in positive ion mode to test the linearity. All commercial polysorbates were analyzed to determine the relative concentration of the components using the same method. RESULTS: The relative peak intensity ratio as a function of the relative concentration ratio was analyzed, and a reasonably good linearity (R(2) = 0.987 for polysorbate 20) was obtained. This study illustrates the process of converting the analyte signal response into the concentration, supporting the notion that quantitative MALDI-TOF MS can be used to analyze polymers. MALDI-TOF MS analysis of commercial polysorbate formulations revealed a complex mixture of oligomers that was related to the fatty acid composition. CONCLUSIONS: Polysorbates 20 and 40 were characterized, and the simultaneous quantitative analysis of polysorbate 20 was reported. This method requires no tedious sample pretreatment. Therefore, it is a promising method for the rapid simultaneous quantitation of polysorbates 20 and 40. PMID- 24214864 TI - Unleashing radical sites in non-covalent complexes: the case of the protonated S nitrosocysteine/18-crown-6 complex. AB - RATIONALE: Introducing radicals onto gas-phase non-covalent complexes and studying their chemistry is a relatively unexplored frontier. In generating these radicals via bond homolysis reactions, it is important that the energy necessary for forming the radical does not exceed the energy required for dissociating the complex itself. Based on this consideration, new approaches for creating these radicals will probably have to involve incorporation of weak bonds that can easily undergo homolysis. METHODS: The formation of a radical cation, via collision-induced dissociation, of protonated S-nitrosocysteine non-covalently bound to the crown ether 18-crown-6 is described here. The radical cation of this complex was isolated and subjected to collisional activation and ion-molecule reactions with allyl iodide. The results were compared with those of the radical cation of 'bare' cysteine. RESULTS: Collisional activation of the radical cation of the cysteine/crown complex led to fragmentation of cysteine as well as of the crown ether. Ion-molecule reactions of the radical cation of the complex with allyl iodide led to products arising from I and allyl abstraction. Isolation and CID of the former product ion led to the loss of iodocysteine. CONCLUSIONS: Cleavage of the weak S-NO bond has allowed the formation of a radical site onto a non-covalent complex. Ion-molecule reactions and collisional activation were utilized to probe the chemistry of this radical cation. The approach adopted here for incorporating a radical onto a cysteine/crown complex shows promise for the introduction of radical sites onto other biological non-covalent complexes. PMID- 24214865 TI - A sensitive method for the sulfur isotope analysis of dimethyl sulfide and dimethylsulfoniopropionate in seawater. AB - RATIONALE: Dimethyl sulfide (DMS) is the major volatile sulfur species emitted to the atmosphere from the oceans. The sulfur isotope ratio ((34)S/(32)S) of DMS may offer a way to calculate the contribution of marine DMS to global sulfur cycling. The S-isotopic analysis of DMS is difficult due to its low concentrations in natural seawater and high chemical reactivity. Here we present a sensitive, precise and accurate method for determining the S-isotopic composition of natural DMS and its precursor, dimethylsulfoniopropionate (DMSP), in seawater. METHODS: The method was based on a purge of DMS from aqueous solutions or natural seawater to a cryogenic trap and subsequent separation of DMS by gas chromatography. The separated DMS was then transferred from the gas chromatograph to a multicollector inductively coupled plasma mass spectrometer (GC/MC-ICPMS system) for measurement of (34)S/(32)S ratios. Correction for mass bias was accomplished using standard sample bracketing with peaks of SF6 as a reference gas. RESULTS: Results obtained from synthetic DMS and DMSP dissolved in artificial seawater show >98% recovery of DMS and very good precision (0.1 to 0.30/00), accuracy and linearity (0.20/00) for the 26-179 picomoles (pmol) of DMS or DMSP injected. The system was tested with natural seawater from Eilat (Red Sea, Israel) and similar precision and accuracy for both DMS and DMSP were obtained. The delta(34)S values of DMS and DMSP from Eilat seawater were 19.2 +/- 0.20/00 and 19.7 +/- 0.20/00, respectively. CONCLUSIONS: The coupling of a purge-and-trap system with a GC/MC ICPMS system was shown to be a sensitive, accurate and robust approach for the S isotope analysis of nanomolar (nM) concentrations of DMS and DMSP from aqueous solutions and natural seawater. PMID- 24214866 TI - Reagent assessment for detection of ammonium ion-molecule complexes. AB - RATIONALE: Ammonia (NH3) is an important chemical target in sensor applications such as trace explosives detection of ammonium nitrate (NH4NO3) and environmental monitoring. Ion-molecule reagent chemistries show potential to increase sensitivity in detection systems relying on atmospheric pressure ionization (API) of reagent-ammonium (M + NH4(+)) complexes. Gas-phase reagent selection assessment is based on mass spectrometric (MS) determination of binding constants relative to competitive ions and critical energies for ion-molecule complex dissociation. METHODS: Eight ammonium complexation reagents were identified and gas-phase ion-molecule interactions were studied using electrospray ionization. Binding constants were determined, in Log(K), using the competition method for one host molecule with three guests (NH4(+), Na(+), and K(+)) in single quadrupole MS. Critical energy determination was based on calibration of threshold activation voltage using collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). RESULTS: This assessment informs selective binding affinity and intrinsic ion-molecule critical energy for dissociation. Relative NH4(+) binding affinity was highest for sucrose and 4-tert-butylcalix[6]arene, while 4-tert-butylcalix[6]arene and methyl acetoacetate showed the highest preferential binding of NH4(+) versus Na(+) and K(+). The intrinsic critical energy for NH4(+) binding was highest for crown ethers, tetraglyme and methyl acetoacetate. CONCLUSIONS: An MS-based framework was developed to quantitatively assess API ion-molecule reagent chemistries based on ammonium selectivity versus competing ions, and intrinsic ammonium binding strength and complex survivability for detection. Methyl acetoacetate is an attractive ammonium reagent for vapor phase API techniques given its high vapor pressure, preferential selectivity, and high critical energy for dissociation. PMID- 24214867 TI - Femtosecond laser-induced ionization/dissociation tandem mass spectrometry (fsLID MS/MS) of deprotonated phosphopeptide anions. AB - RATIONALE: Radical-directed dissociation techniques provide structural information which is complementary to that from conventional collision-induced dissociation (CID). The analysis of phosphopeptide anions is warranted due to their relatively acidic character. As femtosecond laser-induced ionization/dissociation tandem mass spectrometry (fsLID-MS/MS) is uniquely initiated by field ionization, an investigation is warranted to determine whether fsLID may provide novel analytical utility for phosphopeptide anions. METHODS: Twenty-three synthetic deprotonated phosphopeptide anions were introduced into a three-dimensional quadrupole ion trap mass spectrometer via electrospray ionization. The ion trap was interfaced with a near-IR (802 nm) ultrashort-pulsed (35 fs FWHM) ultrahigh-powered (peak power ~10(14) W/cm(2)) laser system. Performance comparisons are made with other techniques applied to phosphopeptide anion analysis, including CID, electron detachment dissociation (EDD), negative electron transfer dissociation (NETD), activated electron photodetachment dissociation (activated-EPD), and ultraviolet photodissociation (UVPD). RESULTS: FsLID-MS/MS of multiply deprotonated phosphopeptide anions provides sequence information via phosphorylation-intact a/x ions in addition to other sequence ions, satellite ions, and side-chain losses. Novel fragmentation processes include selective c-ion formation N-terminal to Ser/Thr and a phosphorylation specific correlation between xn -98 ion abundances and phosphorylation at the n(th) residue. Sequencing-quality data required about 30 s of signal averaging. fsLID-MS/MS of singly deprotonated phosphopeptides did not yield product anions with stable trajectories, despite significant depletion of the precursor. CONCLUSIONS: Multiply deprotonated phosphopeptide anions were sequenced via negative-mode fsLID-MS/MS, with phosphosite localization facilitated by a/x ion series in addition to diagnostic x(n)-98 ions. fsLID-MS/MS is qualitatively competitive with other techniques. Further efficiency enhancements (e.g., implementation on a linear trap or/and higher pulse frequencies) may permit sequence analyses on chromatographic timescales. PMID- 24214868 TI - On-line HfF5(-)/WF5(-) separation in an O2-filled radiofrequency quadrupole gas cell. AB - RATIONALE: An experimental Isobar Separator for Accelerator Mass Spectrometry (ISAMS) instrument has been used to demonstrate an on-line separation of HfF5(-) from its isobar WF5(-). This is necessary, in addition to sample preparation chemistry, for measuring (182)Hf at natural levels by Accelerator Mass Spectrometry (AMS). METHODS: The device utilizes a radiofrequency quadrupole (RFQ) controlled gas cell, wherein anion-gas reactions at eV energies attenuate the interfering isobars of the analyte molecular anions, leaving HfF5(-) for AMS analysis. The RFQ also helps to control the multiple scattering resulting from the ion-gas collisions. RESULTS: O2 gas was used in the HfF5(-)/WF5(-) separation and WF5(-) was attenuated by nearly 3 orders of magnitude while maintaining ~75% transmission of HfF5(-). It is expected that the transmission and attenuation can be increased by further research. CONCLUSIONS: This result advances the possibility of detecting natural (182)Hf when AMS is supplemented with an isobar separator in the injection system. PMID- 24214869 TI - New tetrads formed by deprotonated guanosine molecules and stabilized by alkali earth metal cations, as studied by electrospray ionization mass spectrometry. PMID- 24214870 TI - Dual-beam versus single-beam depth profiling: same sample in same instrument. PMID- 24214871 TI - Kinetic resolution of allyl fluorides by enantioselective allylic trifluoromethylation based on silicon-assisted C-F bond cleavage. AB - Two birds, one stone! The first kinetic resolution of allyl fluorides was achieved by the development of an organocatalyzed enantioselective allylic trifluoromethylation. Two kinds of chiral fluorinated compounds, which incorporate C*?F and C*?CF3 units, respectively, can thus be accessed by a single transformation. PMID- 24214872 TI - Development and validation of a novel method to derive central aortic systolic pressure from the MR aortic distension curve. AB - PURPOSE: Central aortic systolic pressure (CASP) is a more accurate measure of load and cardiovascular risk than brachial pressure. Unfortunately, CASP is difficult to measure using current methods. In this study we report three methods of determining CASP by combining MR-derived aortic area curves with different models of the pressure-area relationship. MATERIALS AND METHODS: CASP was derived by calibrating aortic area curves to the brachial mean and diastolic pressure, using: linear, exponential, and arctangent models in 20 volunteers using a high temporal resolution spiral PC-MR flow sequence. The arctangent model also required calibration with pulse wave velocity. Carotid tonometry CASP was used as the reference standard. RESULTS: Brachial systolic pressure correlated only moderately with carotid CASP r(2) = 0.46 (P = 0.01). However, arctangent, exponential, and linear CASP correlated strongly with carotid CASP, r(2) = 0.90, r(2) = 0.86, r(2) = 0.85, respectively (P < 0.0001). There was excellent agreement between carotid CASP and both arctangent (bias 1.5; SD 3.3) and exponential CASP (bias 0.6; SD 3.6). There was a slight underestimation using the linear model (bias -2.3; SD 3.8) and poor agreement and overestimation using brachial systolic pressure (bias 12.9; SD 8.0). CONCLUSION: We have shown that CASP can be derived from MR data: arctangent and exponential methods being superior to the linear method. The superior correlation of MR derived CASP over brachial systolic BP suggests these measures will allow more comprehensive assessment of systemic arterial hypertension. PMID- 24214873 TI - Selecting patients with hepatocellular carcinoma for liver transplantation: who should receive priority? PMID- 24214874 TI - MicroRNA-21 in the pathogenesis of acute kidney injury. AB - Acute kidney injury (AKI), associated with significant morbidity and mortality, is widely known to involve epithelial apoptosis, excessive inflammation, and fibrosis in response to ischemia or reperfusion injury, which results in either chronic pathological changes or death. Therefore, it is imperative that investigations are conducted in order to find effective, early diagnoses, and therapeutic targets needed to help prevent and treat AKI. However, the mechanisms modulating the pathogenesis of AKI still remain largely undetermined. MicroRNAs (miRNAs), small non-coding RNA molecules, play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expression. MicroRNA-21 (miR-21) is a recently identified, typical miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fibrotic signaling pathways in AKI. As a result, miR-21 is now considered a novel biomarker when diagnosing and treating AKI. This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI. PMID- 24214875 TI - Developing controllable hypermutable Clostridium cells through manipulating its methyl-directed mismatch repair system. AB - Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution. However, there have not been any similar systems developed for Clostridium, an important bacterial genus. Here we report a novel two-step strategy for developing controllable hypermutable cells of Clostridium acetobutylicum, an important and representative industrial strain. Firstly, the mutS/L operon essential for methyldirected mismatch repair (MMR) activity was inactivated from the genome of C. acetobutylicum to generate hypermutable cells with over 250-fold increased mutation rates. Secondly, a proofreading control system carrying an inducibly expressed mutS/L operon was constructed. The hypermutable cells and the proofreading control system were integrated to form a controllable hypermutable system SMBMutC, of which the mutation rates can be regulated by the concentration of anhydrotetracycline (aTc). Duplication of the miniPthl-tetR module of the proofreading control system further significantly expanded the regulatory space of the mutation rates, demonstrating hypermutable Clostridium cells with controllable mutation rates are generated. The developed C. acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress, indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges. PMID- 24214876 TI - IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation. AB - Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell transplantation. An animal model, xenogeneic GVHD (X GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/c-Rag2-/- IL-2RGammac-/- (BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19+ B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19+ CD38(high) plasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the first to find in vivo expansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our findings show evidence of the involvement of B cells in X GVHD and may have implications in the treatment of the disease. PMID- 24214878 TI - Carbonyl oxides--rising stars in tropospheric chemistry. AB - The X factor of tropospheric oxidation: Formaldehyde oxide, the smallest "Criegee intermediate", has been observed spectroscopically in the gas phase. Field studies provide increasing evidence that Criegee intermediates play a key role in tropospheric oxidation. PMID- 24214877 TI - CD1d(hi)CD5+ B cells differentiate into antibody-secreting cells under the stimulation with calreticulin fragment. AB - Calreticulin (CRT) is a multifunctional molecule in both intracellular and extracellular environment. We have previously found that a recombinant CRT fragment (rCRT/39-272) could modulate T cell-mediated immunity in mice via activation and expansion of CD1d(hi)CD5+ B cells as well as induction of CRT specific regulatory antibodies. Antibody secreting cells (ASCs) are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regulation. In this study, we demonstrate that rCRT/39-272 differentiates murine CD1d(hi)CD5+ B cells into ASCs marked by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro. Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1d(hi)CD5+ B cells into ASCs in naive mice or mice with experimental autoimmune encephalomyelitis. Thus, we propose that ASC differentiation and subsequent antibody production of CD1d(hi)CD5+ B cells are key steps in CRT-mediated immunoregulation on inflammatory T cell responses. PMID- 24214880 TI - Modeling population health: reflections on the performativity of epidemiological techniques in the age of genomics. AB - Risk reasoning has become the common-sense mode of knowledge production in the health sciences. Risk assessment techniques of modern epidemiology also co-shape the ways genomic data are translated into population health. Risk computations (e.g., in preventive medicine, clinical decision-support software, or web-based self-tests), loop results from epidemiological studies back into everyday life. Drawing from observations at various European research sites, I analyze how epidemiological techniques mediate and enact the linkages between genomics and public health. This article examines the epidemiological apparatus as a generative machine that is socially performative. The study design and its reshuffling of data and categories in risk modeling recombine old and new categories from census to genomics and realign genes/environment and nature/culture in novel and hybrid ways. In the Euro-American assemblage of risk reasoning and related profiling techniques, the individual and the population are no longer separate but intimately entangled. PMID- 24214881 TI - Vitamin D-binding protein, circulating vitamin D and risk of renal cell carcinoma. AB - Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D-binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes. We conducted a nested case-control analysis within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D. Renal cell carcinoma cases (n = 262) were matched 1:1 to controls on age (+/-1 year) and date of blood collection (+/- 30 days). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of renal cell carcinoma risk by quartiles of 25(OH)D, DBP and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR = 0.17, 95% CI = 0.08-0.33; p-trend < 0.0001), a finding unchanged by adjustment for 25(OH)D. Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D [Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR = 1.61, 95% CI = 0.95-2.73; p-trend = 0.09]. The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D-independent influence of DBP. PMID- 24214884 TI - Transesophageal echocardiography in cryptogenic stroke and patent foramen ovale: analysis of putative high-risk features from the risk of paradoxical embolism database. AB - BACKGROUND: Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), although the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography features such as PFO size, associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these transesophageal echocardiography features with other markers of pathogenicity has not been examined. METHODS AND RESULTS: We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high-risk transesophageal echocardiography features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n=637) compared with those less likely to have a PFO-attributable stroke (n=657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (odds ratio [OR], 0.92; P=0.53). The presence of neither a hypermobile septum nor a right-to-left shunt at rest was detected more often in those with a probable PFO-attributable stroke (OR, 0.80; P=0.45; OR, 1.15; P=0.11, respectively). CONCLUSIONS: We found no evidence that the proposed transesophageal echocardiography risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS. PMID- 24214885 TI - Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: the Atherosclerosis Risk in Communities study. AB - BACKGROUND: Heart failure is an important public health concern, particularly among persons>65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. METHODS AND RESULTS: The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, ~6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2 dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. CONCLUSIONS: We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies. PMID- 24214886 TI - Evaluation of vegetation size and its relationship with embolism in infective endocarditis: a real-time 3-dimensional transesophageal echocardiography study. AB - BACKGROUND: Two-dimensional (2D) echocardiography studies have shown that the maximum length of vegetation (MLV)>=10 mm is a predictor of embolic events (EEs) in patients with infective endocarditis. However, 2D measurements probably underestimate the vegetation dimensions. In this study, we evaluated the feasibility of real-time 3-dimensional transesophageal echocardiography (RT3DTEE) in determining MLV and its accuracy in identifying the risk for EEs compared with 2D transesophageal echocardiography (2DTEE). METHODS AND RESULTS: We analyzed 60 patients with vegetations. RT3DTEE measurement of MLV was obtained with Advanced QLAB Quantification Software by cropping the 3D volume with the appropriate 2D plane to obtain the largest value. The standard 2DTEE images were also evaluated to determine the MLV. Major EEs were registered from medical records, and a logistic regression analysis was performed to determine the association between MLV and EEs. The RT3DTEE MLV was larger than the 2DTEE value with a mean difference of 3.2 mm (95% confidence interval, 2.1-4.2 mm). The best cut-off value for prediction of EEs was MLV>=20 mm with RT3DTEE and MLV>=16 mm with 2DTEE. The positive predictive value increased from 59.1% to 65.2% when RT3DTEE was used. The accuracy of classification of patients with EEs increased from 65% to 70% with this new technique. CONCLUSIONS: RT3DTEE is a feasible technique for the analysis of vegetation morphology and size that may overcome the shortcoming of 2DTEE, leading to a better prediction of the embolism risk in patients with infective endocarditis. PMID- 24214889 TI - Effects of Ni vacancies and crystallite size on the O 1s and Ni 2p x-ray absorption spectra of nanocrystalline NiO. AB - We have studied the electronic structure of nanocrystalline NiO thin films, grown by radio-frequency magnetron sputtering under different experimental conditions, using x-ray absorption spectroscopy. The O 1s and Ni 2p spectra showed distinct changes as a function of O2 content in the plasma, which were reproduced with cluster model calculations. These changes are attributed to the incrementing of the surface contribution due to a decrease of the crystallite size as the O2 content in the plasma increases, and to the presence of induced nickel vacancies. Thus, the changes in the electronic structure can be related to the modification of structural and transport properties of these nanocrystalline films. PMID- 24214887 TI - Thyroid hormones differentially regulate phosphorylation of ERK and Akt via integrin alphavbeta3 receptor in undifferentiated and differentiated PC-12 cells. AB - The effects of 3,5,3'-triiodo-l-thyronine (T3) and l-thyroxine (T4) on the integrin alphavbeta3 receptor of thyroid hormones (TH) were investigated in pheochromocytoma PC-12 cells. Differentiation was induced by treatment of PC-12 cells with fisetin and the levels of phosphorylated extracellular signal regulated kinase (ERK) and Akt in cytoplasm, as well as the content of FoxO6 transcription factor in nuclei was analysed in undifferentiated and differentiated conditions. We have found that in undifferentiated PC-12 cells, tetraiodothyroacetic acid (TETRAC), a known inhibitor of binding of T4 and T3 to plasma membrane integrin alphavbeta3 receptor inhibits T4-dependent phosphorylation of ERK, whereas in differentiated PC-12 cells, TETRAC abolishes the effect of T3. In undifferentiated PC-12 cells, both TH increase the level of p-Akt, and this enhancement is not sensitive to TETRAC. In differentiated PC-12 cells, both TH increase the level of p-Akt; however, only T3-dependent activation of Akt is sensitive to the TETRAC. Furthermore, our results have shown that in differentiated PC-12 cells, the expression of FoxO6 was higher than in undifferentiated PC-12 cells, and this elevation has not changed under the action of TH. Only in undifferentiated PC-12 cells the T3-dependent expression of FoxO6 was sensitive to the TETRAC. We propose that PC-12 cells contain integrin alphavbeta3 receptor, which T3 and T3/T4 sites are differentially regulated by TH in undifferentiated and differentiated conditions. PMID- 24214890 TI - Navigator flip angle optimization for free-breathing T1-weighted hepatobiliary phase imaging with gadoxetic acid. AB - PURPOSE: To characterize and optimize the navigator-flip angle (FA), and the influence of imaging-FA on optimizing liver/lung contrast of the navigator profile, while avoiding visible navigator saturation artifacts, for hepatobiliary phase gadoxetic acid-enhanced MRI. MATERIALS AND METHODS: Ten volunteers; six men, four women; ages 37.1 +/- 11.0 years underwent navigator-gated three dimensional (3D) -spoiled-gradient-echo sequences in randomized combinations of imaging-FA (10 degrees /30 degrees ) and navigator-FA (10-90 degrees ) before contrast and 20 min after injection of gadoxetic acid at 3 Tesla. The signal intensities of the liver and lung were measured from navigator profiles. Furthermore, the intensity of saturation artifacts for each navigator FA was quantified using measurements of relative contrast at the artifact location. RESULTS: For the postcontrast images, the optimal navigator FA was 90 degrees . However, saturation artifacts were highly dependent on the imaging-FA and the presence of gadolinium contrast. A smaller imaging-FA of 10 degrees led to greater saturation artifacts for both pre- and postcontrast, and saturation artifacts worsen with increasing navigator-FA. Using a higher imaging-FA of 30 degrees , saturation artifacts are ignorable over the entire range of navigator FA. CONCLUSION: For navigator-gated gadoxetic acid-enhanced hepatobiliary imaging, navigator-FA of 90 degrees and imaging-FA of 30 degrees provide an optimal balance with maximum navigator liver/lung contrast while avoiding visible imaging saturation artifacts.J. Magn. Reson. Imaging 2014;40:1129-1136. (c) 2013 Wiley Periodicals, Inc. PMID- 24214891 TI - Feasibility of using auto Mod-MPI system, a novel technique for automated measurement of fetal modified myocardial performance index. AB - OBJECTIVES: To evaluate the reproducibility of measurement of the fetal left modified myocardial performance index (Mod-MPI) determined using a novel automated system. METHODS: This was a prospective study of 116 ultrasound examinations from 110 normal singleton pregnancies at 12 + 1 to 37 + 1 weeks' gestation. Two experienced operators each measured the left Mod-MPI twice manually and twice automatically using the Auto Mod-MPI system. Intra- and interoperator reproducibility were assessed using intraclass correlation coefficients (ICCs) and the manual and automated measurements obtained by the more experienced operator were compared using Bland-Altman plots and ICCs. RESULTS: Both operators successfully measured the left Mod-MPI in all cases using the Auto Mod-MPI system. For both operators, intraoperator reproducibility was higher when performing automated measurements (ICC = 0.967 and 0.962 for Operators 1 and 2, respectively) than when performing manual measurements (ICC = 0.857 and 0.856 for Operators 1 and 2, respectively). Interoperator agreement was also better for automated than for manual measurements (ICC = 0.930 vs 0.723, respectively). There was good agreement between the automated and manual values measured by the more experienced operator. CONCLUSIONS: The Auto Mod-MPI system is a reliable technique for measuring fetal left Mod-MPI and demonstrates excellent reproducibility. PMID- 24214893 TI - Interaction between Rice stripe virus disease-specific protein and host PsbP enhances virus symptoms. AB - Rice stripe virus (RSV) causes severe diseases in Oryza sativa (rice) in many Eastern Asian countries. Disease-specific protein (SP) of RSV is a non-structural protein and its accumulation level in rice plant was shown to determine the severity of RSV symptoms. Here, we present evidence that expression of RSV SP alone in rice or Nicotiana benthamiana did not produce visible symptoms. Expression of SP in these two plants, however, enhanced RSV- or Potato virus X (PVX)-induced symptoms. Through yeast two-hybrid screening, GST pull-down, and bimolecular fluorescence complementation assays, we demonstrated that RSV SP interacted with PsbP, a 23-kDa oxygen-evolving complex protein, in both rice and N. benthamiana. Furthermore, our investigation showed that silencing of PsbP expression in both plants increased disease symptom severity and virus accumulation. Confocal microscopy using N. benthamiana protoplast showed that PsbP accumulated predominantly in chloroplast in wild-type N. benthamiana cells. In the presence of RSV SP, most PsbP was recruited into cytoplasm of the assayed cells. In addition, accumulation of SP during RSV infection resulted in alterations of chloroplast structure and function. Our findings shed light on the molecular mechanism underlying RSV disease symptom development. PMID- 24214892 TI - Salt stress in Arabidopsis: lipid transfer protein AZI1 and its control by mitogen-activated protein kinase MPK3. AB - A plant's capability to cope with environmental challenges largely relies on signal transmission through mitogen-activated protein kinase (MAPK) cascades. In Arabidopsis thaliana, MPK3 is particularly strongly associated with numerous abiotic and biotic stress responses. Identification of MPK3 substrates is a milestone towards improving stress resistance in plants. Here, we characterize AZI1, a lipid transfer protein (LTP)-related hybrid proline-rich protein (HyPRP), as a novel target of MPK3. AZI1 is phosphorylated by MPK3 in vitro. As documented by co-immunoprecipitation and bimolecular fluorescence complementation experiments, AZI1 interacts with MPK3 to form protein complexes in planta. Furthermore, null mutants of azi1 are hypersensitive to salt stress, while AZI1 overexpressing lines are markedly more tolerant. AZI1 overexpression in the mpk3 genetic background partially alleviates the salt-hypersensitive phenotype of this mutant, but functional MPK3 appears to be required for the full extent of AZI1 conferred robustness. Notably, this robustness does not come at the expense of normal development. Immunoblot and RT-PCR data point to a role of MPK3 as positive regulator of AZI1 abundance. PMID- 24214894 TI - Fifteen million years of evolution in the Oryza genus shows extensive gene family expansion. AB - In analyzing gene families in the whole-genome sequences available for O. sativa (AA), O. glaberrima (AA), and O. brachyantha (FF), we observed large size expansions in the AA genomes compared to FF genomes for the super-families F-box and NB-ARC, and five additional families: the Aspartic proteases, BTB/POZ proteins (BTB), Glutaredoxins, Trypsin alpha-amylase inhibitor proteins, and Zf Dof proteins. Their evolutionary dynamic was investigated to understand how and why such important size variations are observed between these closely related species. We show that expansions resulted from both amplification, largely by tandem duplications, and contraction by gene losses. For the F-box and NB-ARC gene families, the genes conserved in all species were under strong purifying selection while expanded orthologous genes were under more relaxed purifying selection. In F-box, NB-ARC, and BTB, the expanded groups were enriched in genes with little evidence of expression, in comparison with conserved groups. We also detected 87 loci under positive selection in the expanded groups. These results show that most of the duplicated copies in the expanded groups evolve neutrally after duplication because of functional redundancy but a fraction of these genes were preserved following neofunctionalization. Hence, the lineage-specific expansions observed between Oryza species were partly driven by directional selection. PMID- 24214895 TI - Import determinants of organelle-specific and dual targeting peptides of mitochondria and chloroplasts in Arabidopsis thaliana. AB - Most of the mitochondrial and chloroplastic proteins are synthesized in the cytosol as precursor proteins carrying an N-terminal targeting peptide (TP) directing them specifically to a correct organelle. However, there is a group of proteins that are dually targeted to mitochondria and chloroplasts using an ambiguous N-terminal dual targeting peptide (dTP). Here, we have investigated pattern properties of import determinants of organelle-specific TPs and dTPs combining mathematical multivariate data analysis (MVDA) with in vitro organellar import studies. We have used large datasets of mitochondrial and chloroplastic proteins found in organellar proteomes as well as manually selected data sets of experimentally confirmed organelle-specific TPs and dTPs from Arabidopsis thaliana. Two classes of organelle-specific TPs could be distinguished by MVDA and potential patterns or periodicity in the amino acid sequence contributing to the separation were revealed. dTPs were found to have intermediate sequence features between the organelle-specific TPs. Interestingly, introducing positively charged residues to the dTPs showed clustering towards the mitochondrial TPs in silico and resulted in inhibition of chloroplast, but not mitochondrial import in in vitro organellar import studies. These findings suggest that positive charges in the N-terminal region of TPs may function as an 'avoidance signal' for the chloroplast import. PMID- 24214896 TI - Optimizing trial design in pharmacogenetics research: comparing a fixed parallel group, group sequential, and adaptive selection design on sample size requirements. AB - Two-stage clinical trial designs may be efficient in pharmacogenetics research when there is some but inconclusive evidence of effect modification by a genomic marker. Two-stage designs allow to stop early for efficacy or futility and can offer the additional opportunity to enrich the study population to a specific patient subgroup after an interim analysis. This study compared sample size requirements for fixed parallel group, group sequential, and adaptive selection designs with equal overall power and control of the family-wise type I error rate. The designs were evaluated across scenarios that defined the effect sizes in the marker positive and marker negative subgroups and the prevalence of marker positive patients in the overall study population. Effect sizes were chosen to reflect realistic planning scenarios, where at least some effect is present in the marker negative subgroup. In addition, scenarios were considered in which the assumed 'true' subgroup effects (i.e., the postulated effects) differed from those hypothesized at the planning stage. As expected, both two-stage designs generally required fewer patients than a fixed parallel group design, and the advantage increased as the difference between subgroups increased. The adaptive selection design added little further reduction in sample size, as compared with the group sequential design, when the postulated effect sizes were equal to those hypothesized at the planning stage. However, when the postulated effects deviated strongly in favor of enrichment, the comparative advantage of the adaptive selection design increased, which precisely reflects the adaptive nature of the design. PMID- 24214898 TI - Myo-inositol trispyrophosphate-mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy. AB - Hypoxia and dysfunctional tumor vessels represent a prominent feature of pancreatic cancer, being, at least in part, responsible for chemotherapy resistance and immune suppression in these tumors. We tested whether the increase of oxygen delivery induced in vivo by myo-inositol trispyrophosphate (ITPP) can reverse hypoxia, control tumor growth and improve chemotherapy response. Tumor size, metastatic development (microcomputed tomography scan follow-up) and the survival of rats and nude or NOD.SCID mice, (bearing syngenic rat and MiaPaCa2- or patient-derived pancreatic tumors), were determined on ITPP and/or gemcitabine treatment. Partial oxygen pressure, expression of angiogenic factors and tumor histology were evaluated. Infiltration and oxidative status of immune cells, as well as chemotherapy penetration in tumors, were determined by fluorescence activated cell sorting, fluorometry, nitric oxide release assays, Western blot and confocal microscopy. Weekly intravenous ITPP application resulted in the inhibition of metastasis development and restricted primary tumor growth, showing a superior effect on the rats' survival compared with gemcitabine. ITPP treatment restored tumor normoxia and caused a reduction in hypoxia inducible factor-1alpha levels, with subsequent VEGF and Lox downregulation, resulting in improved vessel structure and decreased desmoplasia. The latter effects translated into elevated immune cells influx and improved susceptibility to gemcitabine treatment. Growth of human pancreatic tumor xenografts was strongly inhibited by administration of ITPP. ITPP exploits a two-stage mechanism causing rapid, early and sustainable late stage normoxia. This is due to the angiogenic factor modulation and vascular normalization, leading to enhanced chemotherapy delivery and synergistic life prolongation, on combination with low doses of gemcitabine. PMID- 24214899 TI - In vitro and in vivo supramolecular modification of biomembranes using a lipidated coiled-coil motif. PMID- 24214900 TI - Laser versus conventional fenestration in stapedotomy for otosclerosis: a systematic review. AB - OBJECTIVES/HYPOTHESIS: To assess hearing results and complications following primary stapedotomy in otosclerosis patients comparing the use of laser and conventional techniques for fenestration. STUDY DESIGN: Systematic literature review. METHODS: A systematic bibliographic search was conducted in PubMed, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus. Studies reporting original data on the effect of laser fenestration, compared to conventional techniques, on closure of air-bone gap in patients undergoing primary stapedotomy were included. Directness of evidence and risk of bias of the selected articles were assessed. Studies with low directness of evidence, high risk of bias, or both were not further analyzed. The absolute risks, risk differences, and 95% confidence intervals were extracted only for studies with moderate to high directness of evidence and moderate to low risk of bias. RESULTS: In total, 383 unique studies were retrieved. Eight of these (including 999 procedures) provided high or moderate directness of evidence and carried a moderate risk of bias, and were considered eligible for data extraction. The included studies show no consistent difference in postoperative air-bone gap closure or immediate postoperative vertigo. CONCLUSIONS: Both footplate fractures and sensorineural hearing loss appear to occur more frequently in the conventional group than in the laser group. Therefore, we prefer laser above conventional methods for footplate fenestration in primary stapedotomy. LEVEL OF EVIDENCE: NA. PMID- 24214902 TI - A detailed study of the magnetic phase transition in CuCrO2. AB - The phase transition in CuCrO2 to an ordered magnetic state is studied with bulk measurements and elastic and inelastic neutron scattering techniques. The reported onset of spontaneous electric polarization at T = 23.5 K coincides with the appearance, on cooling, of elastic magnetic scattering. At higher temperatures long range magnetic correlations gradually develop but they are dynamic. The ground state is characterized by three-dimensional long range magnetic ordering but along the c direction the correlation length remains limited to ~200 A. PMID- 24214901 TI - Prevalence and prognostic importance of changes in renal function after mechanical circulatory support. AB - BACKGROUND: The long-term durability and prognostic significance of improvement in renal function after mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality. METHODS AND RESULTS: Adult patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with serial creatinine levels available (n=3363) were studied. Early post-MCS, eGFR improved substantially (median improvement, 48.9%; P<0.001) with 22.3% of the population improving their eGFR by >=100% within the first few weeks. However, in the majority of patients, this improvement was transient, and by 1 year, eGFR was only 6.7% above the pre-MCS value (P<0.001). This pattern of early improvement followed by deterioration in eGFR was observed with both pulsatile and continuous flow devices. Interestingly, poor survival was associated with both marked improvement (adjusted hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.19 2.26; P=0.002) and worsening in eGFR (adjusted HR, 1.63; 95% CI, 1.15-2.13; P=0.004). CONCLUSIONS: Post-MCS, early improvement in renal function is common but seems to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119834. PMID- 24214903 TI - Selective palladium-catalyzed aminocarbonylation of olefins with aromatic amines and nitroarenes. PMID- 24214904 TI - Gadolinium-free T1 contrast agents for MRI: tunable pharmacokinetics of a new class of manganese porphyrins. AB - PURPOSE: To evaluate a new class of manganese porphyrins with tunable pharmacokinetics as potential gadolinium (Gd)-free T1 agents for contrast enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Two new contrast agents, MnTCP and MnP2, were evaluated in four female rats. MRI was performed daily up to 3 days postinjection (0.05 mmol/kg) on a 3 T clinical scanner. T1 relaxation times and dynamic contrast-enhanced MRI were performed to assess contrast enhancement and clearance in blood, heart, liver, kidney, and muscle. RESULTS: Relative T1 decreases were similar for MnTCP and Gd-DTPA in all tissues but were significantly larger (P < 0.05) for MnP2 in blood, heart, kidney, and liver (2-6-fold larger). Clearance of MnTCP was similar to Gd-DTPA, with T1 returning to baseline by 40 minutes and complete elimination in 1 day. MnP2 was cleared from blood after 2 days and sustained a lowered T1 in other tissues for at least 1 hour (P < 0.05). The maximum enhancement, slope, and time to-peak were similar between contrast agents. Only the parameter AUC60 differed, with MnP2 yielding the largest AUC60 values primarily through longer retention in tissue. CONCLUSION: MnTCP and MnP2 offer distinct applications as Gd-free T1 contrast agents. MnTCP behaves like a Gd-DTPA analog, while MnP2 provides significantly greater and longer positive signal enhancement. PMID- 24214905 TI - Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. AB - OBJECTIVES: As morbidly obese patients are prone to surgical site infections, adequate blood and subcutaneous tissue concentrations of prophylactic antibiotic agents during surgery are imperative. In this study we evaluated cefazolin subcutaneous adipose tissue distribution in morbidly obese and non-obese patients, thereby quantifying the influence of morbid obesity on cefazolin pharmacokinetics and enabling Monte Carlo simulations for subsequent dose adjustments. METHODS: Nine morbidly obese patients [body mass index (BMI) 47 +/- 6 kg/m(2)], of whom eight were evaluable, and seven non-obese patients (BMI 28 +/ 3 kg/m(2)) received cefazolin 2 g intravenously before surgery (NCT01309152). Using microdialysis, interstitial space fluid (ISF) samples of subcutaneous adipose tissue were collected together with total and unbound plasma cefazolin samples until 240 min after dosing. Using NONMEM, population pharmacokinetic modelling, covariate analysis and Monte Carlo simulations were performed. RESULTS: The unbound (free) cefazolin ISF penetration ratio (fAUC(tissue)/fAUC(plasma)) was 0.70 (range 0.68-0.83) in morbidly obese patients versus 1.02 (range 0.85-1.41) in non-obese patients (P < 0.05). A two-compartment model with saturable protein binding was identified in which the central volume of distribution and cefazolin distribution from the central compartment to the ISF compartment proved dependent on body weight (P < 0.001 and P < 0.01, respectively). Monte Carlo simulations showed reduced probability of target attainment for morbidly obese versus non-obese patients for MIC values of 2 and 4 mg/L. CONCLUSIONS: This study shows that cefazolin tissue distribution is lower in morbidly obese patients and reduces with increasing body weight, and that dose adjustments are required in this patient group. PMID- 24214906 TI - Introduction: public health genomics-anthropological interventions in the quest for molecular medicine. AB - We introduce this special issue of Medial Anthropology Quarterly on public health genomics by exploring both the unique contribution of ethnographic sensibility that medical anthropologists bring to the study of genomics and some of the key insights offered by the essays in this collection. As anthropologists, we are concerned with the power dynamics and larger cultural commitments embedded in practices associated with public health. We seek to understand, first, the broad significance of genomics as a cultural object and, second, the social action set into motion as researchers seek to translate genomic knowledge and technology into public health benefits. PMID- 24214908 TI - Monte Carlo calculation of artificial radionuclide radiation dose rates for marine species in the Western Pacific. AB - After the Fukushima nuclear accident, there is a widespread concern over the radioactive contamination of the marine environment. To protect non-human species, a radiation dose rate calculation model for Western Pacific marine species was established. Ten kinds of marine species in the Western Pacific were modelled by Geant4 for Monte Carlo simulation. Organisms were modelled with two ellipsoids: one represented organs and the other represented muscle. The enhanced dose rates by 10 main kinds of nuclides were calculated. According to the reported activities of three main nuclides ((134)Cs, (137)Cs and (131)I) in seawater near Fukushima coastal, the radiation risks of marine species were estimated. The results showed that the marine species near the Fukushima accident drain outlets might be at risk. But organisms that were >15 km away from the drain outlets were relatively safe. PMID- 24214907 TI - Solution properties of gamma-crystallins: compact structure and low frictional ratio are conserved properties of diverse gamma-crystallins. AB - gamma-crystallins are highly specialized proteins of the vertebrate eye lens where they survive without turnover under high molecular crowding while maintaining transparency. They share a tightly folded structural template but there are striking differences among species. Their amino acid compositions are unusual. Even in mammals, gamma-crystallins have high contents of sulfur containing methionine and cysteine, but this reaches extremes in fish gammaM crystallins with up to 15% Met. In addition, fish gammaM-crystallins do not conserve the paired tryptophan residues found in each domain in mammalian gamma crystallins and in the related beta-crystallins. To gain insight into important, evolutionarily conserved properties and functionality of gamma-crystallins, zebrafish (Danio rerio) gammaM2b and gammaM7 were compared with mouse gammaS and human gammaD. For all four proteins, far UV CD spectra showed the expected beta sheet secondary structure. Like the mammalian proteins, gammaM7 was highly soluble but gammaM2b was much less so. The heat and denaturant stability of both fish proteins was lower than either mammalian protein. The ability of full-length and truncated versions of human alphaB-crystallin to retard aggregation of the heat denatured proteins also showed differences. However, when solution behavior was investigated by sedimentation velocity experiments, the diverse gamma crystallins showed remarkably similar hydrodynamic properties with low frictional ratios and partial specific volumes. The solution behavior of gamma-crystallins, with highly compact structures suited for the densely packed environment of the lens, seems to be highly conserved and appears largely independent of amino acid composition. PMID- 24214909 TI - Determination of gamma radioactivity levels and associated dose rates of soil samples of the Akkuyu/Mersin using high-resolution gamma-ray spectrometry. AB - In this study several soil samples were collected from the Buyukeceli district where Turkey's first nuclear power plant will be built and radioactivity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs were determined by gamma spectrometry using a high-purity germanium detector. The measured activity concentrations in soil samples ranged from 9.8 +/- 0.7 to 258.6 +/- 15.8, 11.7 +/ 0.9 to 85.6 +/- 5.0, 173.8 +/- 2.1 to 1949.5 +/- 14.7 and 0.4 +/- 0.1 to 72.2 +/ 2.2 Bq kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, respectively. Findings are in good agreement with the published results of neighbouring areas. The absorbed gamma dose rate (D) in air and the annual effective dose of soil samples were calculated to be 80.2 nGy h(-1) and 98.3 mSv y(-1), respectively. The results show that the radiation hazard in the Buyukeceli district is insignificant. The data presented in this study would be very useful to determine the future effects of the nuclear power plant to the environment. PMID- 24214910 TI - A fast and simple approach for the estimation of a radiological source from localised measurements after the explosion of a radiological dispersal device. AB - After an explosion of a radiological dispersal device, decision-makers need to implement countermeasures as soon as possible to minimise the radiation-induced risks to the population. In this work, the authors present a tool, which can help providing information about the approximate size of source term and radioactive contamination based on a Gaussian Plume model with the use of available measurements for liquid or aerosolised radioactivity. For two-field tests, the source term and spatial distribution of deposited radioactivity are estimated. A sensitivity analysis of the dependence on deposition velocity is carried out. In case of weak winds, a diffusive process along the wind direction is retained in the model. PMID- 24214911 TI - A survey of gross alpha and gross beta activity in soil samples in Kinta District, Perak, Malaysia. AB - The objective of this study was to determine the gross alpha and gross beta activity concentrations from the different soil types found in the Kinta District, Perak, Malaysia. A total of 128 soil samples were collected and their dose rates were measured 1 m above the ground. Gross alpha and gross beta activity measurements were carried out using gas flow proportional counter, Tennelec Series 5 LB5500 Automatic Low Background Counting System. The alpha activity concentration ranged from 15 to 9634 Bq kg(-1) with a mean value of 1558+/-121 Bq kg(-1). The beta activity concentration ranged from 142 to 6173 Bq kg(-1) with a mean value of 1112+/-32 Bq kg(-1). High alpha and beta activity concentrations are from the same soil type. The results of the analysis show a strong correlation between the gross alpha activity concentration and dose rate (R = 0.92). The data obtained can be used as a database for each soil type. PMID- 24214912 TI - Gamma spectrometry efficiency calibration using Monte Carlo methods to measure radioactivity of 137Cs in food samples. AB - A simple method of efficiency calibration for gamma spectrometry was performed. This method, which focused on measuring the radioactivity of (137)Cs in food samples, was based on Monte Carlo simulations available in the free-of-charge toolkit GEANT4. Experimentally, the efficiency values of a high-purity germanium detector were calculated for three reference materials representing three different food items. These efficiency values were compared with their counterparts produced by a computer code that simulated experimental conditions. Interestingly, the output of the simulation code was in acceptable agreement with the experimental findings, thus validating the proposed method. PMID- 24214913 TI - T-cell factor 4 and beta-catenin chromatin occupancies pattern zonal liver metabolism in mice. AB - beta-catenin signaling can be both a physiological and oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20%-40% of hepatocellular carcinomas (HCCs) with specific metabolic features. We decipher the molecular determinants of beta-catenin-dependent zonal transcription using mice with beta-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by T-cell factor (Tcf)-4 and beta-catenin, transcriptome, and metabolome. We find that Tcf-4 DNA bindings depend on beta catenin. Tcf-4/beta-catenin binds Wnt-responsive elements preferentially around beta-catenin-induced genes. In contrast, genes repressed by beta-catenin bind Tcf 4 on hepatocyte nuclear factor 4 (Hnf-4)-responsive elements. beta-Catenin, Tcf 4, and Hnf-4alpha interact, dictating beta-catenin transcription, which is antagonistic to that elicited by Hnf-4alpha. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by beta-catenin, partly through xenobiotic nuclear receptors. CONCLUSIONS: beta-catenin patterns the zonal liver together with Tcf-4, Hnf-4alpha, and xenobiotic nuclear receptors. This network represses lipid metabolism and exacerbates glutamine, drug, and bile metabolism, mirroring HCCs with beta-catenin mutational activation. PMID- 24214915 TI - Gating charge recombination rates through dynamic bridges in tetrathiafulvalene fullerene architectures. PMID- 24214914 TI - Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-beta. AB - Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor sites, where they can integrate into the tumor-associated stroma. However, molecular mechanisms and outcome of their interaction with cancer cells have not been fully clarified. In this study, we investigated the effects mediated by bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC triggered epithelial-to-mesenchymal transition (EMT) in tumor cells in vitro, as indicated by upregulation of EMT-related genes, downregulation of E-cadherin and acquisition of mesenchymal morphology. These effects required cell-to-cell contact and were mediated by surface-bound TGF-beta newly expressed on MSC upon coculture with tumor cells. In vivo tumor masses formed by MSC-conditioned CRC cells were larger and characterized by higher vessel density, decreased E cadherin expression and increased expression of mesenchymal markers. Furthermore, MSC-conditioned tumor cells displayed increased invasiveness in vitro and enhanced capacity to invade peripheral tissues in vivo. Thus, by promoting EMT related phenomena, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. PMID- 24214916 TI - Two-photon-triggered drug delivery in cancer cells using nanoimpellers. AB - A therapy of cancer cells: Two-photon-triggered camptothecin delivery with nanoimpellers was studied in MCF-7 breast cancer cells. A fluorophore with a high two-photon absorption cross-section was first incorporated in the nanoimpellers. Fluorescence resonance energy transfer (FRET) from the fluorophore to the azobenzene moiety was demonstrated. PMID- 24214918 TI - The magnetocaloric effect in Er2Fe17 near the magnetic phase transition. AB - Recent investigations in R2Fe17 intermetallic compounds have evidenced that these materials present a moderate magnetocaloric effect (MCE) near room temperature. A series of accurate magnetization measurements was carried out to show that the value of the demagnetizing factor has a significant influence on the absolute MCE value of Er2Fe17. In addition, the critical exponents determined from heat capacity and magnetization measurements allow us to describe the field dependence of the observed MCE around the Curie temperature. PMID- 24214917 TI - Porcine small intestine submucosal grafts for post-tumor resection orbital reconstruction. AB - OBJECTIVES/HYPOTHESIS: Removal of the medial orbital wall for sinonasal tumor involvement is required to obtain complete oncologic resection. However, orbital fat herniation can produce significant morbidity, including enophthalmos and diplopia. The purpose of the current study was to evaluate outcomes following use of porcine small intestine submucosa (SIS) grafts for orbital reconstruction following extirpation of sinonasal malignancies. STUDY DESIGN: Case series in a tertiary hospital setting. METHODS: Review of prospectively collected data regarding orbital reconstruction using SIS was performed. Demographics, tumor histology, size of orbital defect, adjuvant treatment, clinical status, and complications were recorded. RESULTS: Seventeen patients (average age, 58 years; range, 27-82 years) had SIS grafting of the medial orbital wall over a 5-year period at our tertiary academic institution. The average orbital wall defect size was 4.6 cm(2) (range, 1 cm(2)-24 cm(2)). Tumor histopathology included esthesioneuroblastoma (n = 5), squamous cell carcinoma (n = 4), adenocarcinoma (n = 2), sinonasal undifferentiated carcinoma (n = 2), melanoma (n = 3), and neuroendocrine carcinoma (n = 1). Surgical goals were curative intent in all patients. Ten patients had postoperative radiation therapy, whereas five individuals had surgical extirpation following neoadjuvant chemotherapy and radiation. All patients had complete locoregional control at last clinical follow up (average, 16 months; range, 2-54 months), although three patients developed distant metastases. The only orbital complications noted were enophthalmos (n = 1), periorbital cellulitis (n = 1), and orbital wall crusting (n = 1). CONCLUSIONS: SIS reconstruction of orbital wall defects was effective in the current series of patients, with only one patient developing noticeable enophthalmos and a low incidence of surgical complications. LEVEL OF EVIDENCE: 4. PMID- 24214919 TI - Quantification of cerebral blood flow in healthy volunteers and type 1 diabetic patients: comparison of MRI arterial spin labeling and [(15)O]H2O positron emission tomography (PET). AB - PURPOSE: To compare cerebral blood flow (CBF) values measured using magnetic resonance imaging (MRI) arterial spin labeling (ASL) with those obtained with [(15)O]H2O positron emission tomography (PET), the gold standard for measuring CBF in vivo. MATERIALS AND METHODS: Data were collected in 11 healthy men and in 20 age- and body mass index (BMI)-matched type 1 diabetic men. Pseudo-continuous ASL (PCASL) data were acquired at 3 T and [(15)O]H2O PET scans were acquired using a high-resolution PET scanner. Input functions were obtained using on-line arterial blood sampling. Whole brain and regional CBF values were compared. RESULTS: For both modalities, whole brain CBF was similar in both subject groups. In groups combined, average whole brain CBF was 0.30 +/- 0.05 mL . cm(-3) . min( 1) for [(15)O]H2O PET and 0.34 +/- 0.05 mL . cm(-3) . min(-1) for ASL MRI (P < 0.01). A significant correlation between methods was observed for whole brain, gray and white matter. In 12 out of 33 brain regions a significant difference between methods was observed. CONCLUSION: PCASL provides CBF values that correlate with [(15)O]H2O PET-derived values, but is less accurate. PCASL may be an attractive alternative when absolute quantification is not needed. PMID- 24214920 TI - Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection. AB - The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non-1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. CONCLUSIONS: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country-wide analysis of treatment and response among HCV infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across England. PMID- 24214922 TI - Are we refereeing ourselves to death? The peer-review system at its limit. PMID- 24214921 TI - Temporal and spatial neural dynamics in the perception of basic emotions from complex scenes. AB - The different temporal dynamics of emotions are critical to understand their evolutionary role in the regulation of interactions with the surrounding environment. Here, we investigated the temporal dynamics underlying the perception of four basic emotions from complex scenes varying in valence and arousal (fear, disgust, happiness and sadness) with the millisecond time resolution of Electroencephalography (EEG). Event-related potentials were computed and each emotion showed a specific temporal profile, as revealed by distinct time segments of significant differences from the neutral scenes. Fear perception elicited significant activity at the earliest time segments, followed by disgust, happiness and sadness. Moreover, fear, disgust and happiness were characterized by two time segments of significant activity, whereas sadness showed only one long-latency time segment of activity. Multidimensional scaling was used to assess the correspondence between neural temporal dynamics and the subjective experience elicited by the four emotions in a subsequent behavioral task. We found a high coherence between these two classes of data, indicating that psychological categories defining emotions have a close correspondence at the brain level in terms of neural temporal dynamics. Finally, we localized the brain regions of time-dependent activity for each emotion and time segment with the low-resolution brain electromagnetic tomography. Fear and disgust showed widely distributed activations, predominantly in the right hemisphere. Happiness activated a number of areas mostly in the left hemisphere, whereas sadness showed a limited number of active areas at late latency. The present findings indicate that the neural signature of basic emotions can emerge as the byproduct of dynamic spatiotemporal brain networks as investigated with millisecond-range resolution, rather than in time-independent areas involved uniquely in the processing one specific emotion. PMID- 24214923 TI - Long axis strain by MRI and echocardiography in a postmyocardial infarct population. AB - PURPOSE: To compare long axis strain (LAS) by magnetic resonance imaging (MRI) and echocardiography in a postinfarct patient population. Long axis left ventricle (LV) function is a sensitive index of incipient heart failure by echocardiography, but is less well established in MRI. LAS is an index of global LV function, which is easily assessed in cine loops provided by most cardiac MRI protocols. MATERIALS AND METHODS: In all, 116 patients (57 +/- 9 years) were studied the same day using echocardiography and MRI 7.4 +/- 4.1 months after a first myocardial infarction. LV length was measured in end diastole and end systole in conventional cine images with a temporal resolution of 50 msec or less, and LAS (%) was calculated as the change in LV length, relative to end diastole. Infarct mass was assessed by contrast-enhanced MRI. RESULTS: LAS was progressively reduced in patients with larger infarcts, and demonstrated good correlations with infarct mass (r = 0.55, P < 0.01). There was a good agreement between LAS assessed by echocardiography and MRI (r = 0.77, P < 0.01), and between LAS by MRI and speckle tracking strain by echocardiography (r = 0.74, P < 0.01). CONCLUSION: LAS is an index that allows measurement of LV long axis function by conventional cine MRI. PMID- 24214924 TI - Does chronic hepatitis E virus infection exist in immunocompetent patients? PMID- 24214925 TI - Short-term exercise-induced changes in hydration state of healthy Achilles tendons can be visualized by effects of off-resonant radiofrequency saturation in a three-dimensional ultrashort echo time MRI sequence applied at 3 Tesla. AB - PURPOSE: Off-resonant RF saturation influences signal intensity dependent on free and bound water fractions as well as the macromolecular content. The extent of interaction between these compartments can be evaluated by using the off resonance saturation ratio (OSR). Combined with UTE sequences quantification of OSR even in tendinous tissues with extremely fast signal decay is possible. The aim of this prospective study was to investigate short-term exercise-induced effects of hydration state of the Achilles tendon by means of OSR and tendon volume. MATERIALS AND METHODS: Measurements of OSR and tendon volume before and after ankle-straining activity were performed in seven healthy male volunteers (median age 29 years) using a 3D UTE sequence with implemented off-resonance saturation pulse at 3T (off-resonance frequency 2/3 kHz) and by an automated contour detection in isotropic T2-weighted MR images with sub-millimeter resolution, respectively. Different tendon regions were evaluated. Reproducibility of OSR was measured in subsequent imaging sets. Root-mean-square deviation (RMSD) and coefficient of variations (CV) were determined. RESULTS: RMSD of OSR in resting position were between 0.006 and 0.01 for different tendon regions and off-resonance frequencies (CV 2 to 3%). A significant increase (P < 0.05) of OSR after exercise was seen in all tendon regions except at the insertion (off-resonance frequency 3 kHz). Tendon volume was decreased significantly after ankle-straining activity (P = 0.003). CONCLUSION: The observed decreased tendon volume and increased OSR directly after exercise indicates a short-term change in tendinous proton compartments, most likely a loss of free water molecules within the tendon. PMID- 24214926 TI - Ultra-low velocity knee dislocations: patient characteristics, complications, and outcomes. AB - BACKGROUND: Knee dislocations resulting in multiligament knee injuries (MLIs) are usually associated with high-energy mechanisms such as motor vehicle accidents or sports injuries; however, obese patients are at risk of MLIs from simple falls. Termed "ultra-low velocity" (ULV) dislocations, these injuries occur in obese patients during activities of daily living and may be associated with higher associated risks and complications. HYPOTHESIS: Ultra-low velocity knee dislocations occur more commonly in obese female patients, are associated with higher risks of neurovascular injuries, and have more significant perioperative complications compared with other MLIs. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The records of 215 consecutive patients with MLIs were identified over a 12-year period. Their charts were reviewed to identify a cohort of patients with mechanisms consistent with ULV dislocations (n = 23). This cohort was compared with all patients with MLIs. Additionally, ULV patients with neurovascular injuries were compared with those without neurovascular injuries. RESULTS: The average body mass index (BMI) was significantly higher in the ULV cohort (49.1 kg/m2) compared with all patients with MLIs (34.1 kg/m2). Injuries occurred more commonly in female patients in the ULV cohort (69.6%) compared with all patients with MLIs (24.3%). Peroneal nerve injuries occurred more commonly in the ULV cohort (39.1%) compared with all patients with MLIs (8.4%), as did vascular injuries (28.1% vs. 4.7%, respectively). Postoperative complications were common among all ULV-MLI patients regardless of neurovascular injury status. Seventeen patients (6/12 in the intact group and 11/11 in the neurovascular injury group) had significant complications postoperatively. A significantly higher overall complication rate was noted in the ULV-MLI group (73.9%) compared with the entire MLI cohort (21.4%). Additionally, the ULV-MLI cohort had a higher reoperation rate, wound infection rate, deep venous thrombosis rate, and presence of vascular claudication. CONCLUSION: Ultra-low velocity knee injuries occur in patients with a greater BMI, more frequently in female patients, and with higher rates of concomitant neurovascular injuries compared with other MLIs. Additionally, a significantly greater incidence of postoperative complications can be expected after ligament reconstruction in this population compared with other MLIs. PMID- 24214927 TI - Hip and glenohumeral rotational range of motion in healthy professional baseball pitchers and position players. AB - BACKGROUND: Research suggests that limitations in the hip motion of baseball players may lead to altered motion at the glenohumeral joint to maintain throwing velocity, thereby predisposing the upper extremity to injury. PURPOSE: To measure and evaluate the correlation between hip and shoulder rotational range of motion (ROM) in healthy professional baseball players. STUDY DESIGN: Descriptive laboratory study. METHODS: Ninety-nine professional baseball players (50 pitchers and 49 position players; mean age +/- standard deviation [SD], 22 +/- 2.8 years; mean height +/- SD, 187 +/- 5.4 cm; mean weight +/- SD, 81.6 +/- 7.7 kg) with no history of hip or shoulder injury were tested. Dominant and nondominant hip and glenohumeral joints were measured for the following passive ROM variables: (1) hip internal rotation (IR), (2) hip external rotation (ER), (3) total hip rotational ROM (IR + ER), (4) isolated glenohumeral IR, (5) isolated glenohumeral ER, and (6) total glenohumeral rotational ROM (IR + ER). RESULTS: Statistically, hip ER and total hip rotational ROM were greater in position players than in pitchers and less in the lead leg compared with the stance leg hip with groups combined; however, differences are not clinically meaningful. Pitchers had more glenohumeral rotational ROM than did position players. For all players, glenohumeral motion had less IR and greater ER in the throwing arm than the nonthrowing arm, but total glenohumeral rotational ROM was equivalent between sides. The correlations between hip and glenohumeral ROM were little, if any, and ranged from r = -0.19 to 0.11 (P = .006-.94) for all players and r = -0.29 to 0.23 (P = .04-.97) for pitchers only. CONCLUSION: These data suggest no clinically meaningful differences in hip ROM between pitchers and position players and between lead leg and stance legs of all players. There is little or no relationship between hip and glenohumeral ROM in healthy professional baseball players. CLINICAL RELEVANCE: The study findings add to the growing body of evidence that suggests an absence of chronic hip ROM adaptations. It is therefore suggested that in the hip, unlike the glenohumeral joint, symmetry in ROM between player positions and dominant and nondominant sides should be expected in healthy professional baseball pitchers and position players. PMID- 24214928 TI - Arthroscopic meniscus allograft transplantation in male professional soccer players: a 36-month follow-up study. AB - BACKGROUND: Meniscus allograft transplantation (MAT) is an option for symptomatic patients who have undergone subtotal meniscectomy and can potentially result in pain relief and increased function. HYPOTHESIS: Professional soccer players would benefit from arthroscopic MAT in terms of pain, knee function, and return to play at 36-month follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twelve male patients who had undergone MAT (6 medial, 6 lateral) were prospectively evaluated at 12- and 36-month follow-up. The mean age at the time of surgery was 24.5 +/- 3.6 years (range, 19-29 years), and the mean time from meniscectomy to surgery was 37 +/- 31 months (range, 2-82 months). The transplantation was performed in patients who had undergone subtotal meniscectomy using an arthroscopic bone plug-free technique with a single tibial tunnel plus "all-inside" meniscus sutures. The anterior horn of the transplanted meniscus was sutured to the capsule and to the remnant of the anterior horn of the native meniscus. Seven patients (58%) underwent concurrent procedures. All patients were evaluated at follow-up by the Tegner, Lysholm, International Knee Documentation Committee (IKDC) subjective, IKDC objective, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog scale (VAS) for pain scores. Information regarding rehabilitation, return to play, and return to official competition was recorded. RESULTS: Eleven of the 12 patients (92%) returned to play soccer. At 36-month follow-up, 9 patients (75%) were still playing as professionals (Tegner score of 10), whereas 2 patients (17%) were playing as semiprofessionals (Tegner score of 9). The mean time from surgery to the end of rehabilitation was 7.5 +/- 2 months, whereas the mean time to official competition was 10.5 +/- 2.6 months. Patients demonstrated significant improvements on the median Tegner score from 8 (interquartile range, 3-10) to 10 (interquartile range, 9-10) (P = .0391); the mean Lysholm score from 67 +/- 14 to 92 +/- 10 (P = .0021); the mean IKDC subjective score from 61.8 +/- 16.3 to 85.3 +/- 9.8 (P = .0026); the mean IKDC objective score from 1 A, 8 B, 1 C, and 2 D to 7 A and 5 B (P = .0077); the mean WOMAC score from 77.1 +/- 15.9 to 92.2 +/- 9.1 (P = .0242); and the mean VAS score from 61 +/- 16 to 29 +/- 32 (P = .0029) at 12 month follow-up. There were no significant improvements in these outcomes at 36 month follow-up. One patient developed a knee infection after MAT plus anterior cruciate ligament allograft reconstruction. This complication was successfully treated, but the patient stopped playing soccer (Tegner score of 3 at 36-month follow-up), and this was considered a failure (8%). CONCLUSION: Arthroscopic MAT in professional soccer players allowed a return to play at the same level (Tegner score of 10) in 75% of the cases at 36-month follow-up. PMID- 24214929 TI - Anterior cruciate ligament injury and radiologic progression of knee osteoarthritis: a systematic review and meta-analysis. AB - BACKGROUND: Knee osteoarthritis after anterior cruciate ligament (ACL) injury has previously been reported. However, there has been no meta-analysis reporting the development and progression of osteoarthritis. PURPOSE: We present the first meta analysis reporting on the development and progression of osteoarthritis after ACL injury at a minimum mean follow-up of 10 years, using a single and widely accepted radiologic classification, the Kellgren & Lawrence classification. STUDY DESIGN: Meta-analysis. METHOD: Articles were included for systematic review if they reported radiologic findings of ACL-injured knees and controls using the Kellgren & Lawrence classification at a minimum mean follow-up period of 10 years. Appropriate studies were then included for meta-analysis. RESULTS: Nine studies were included for systematic review, of which 6 studies were further included for meta-analysis. One hundred twenty-one of 596 (20.3%) ACL-injured knees had moderate or severe radiologic changes (Kellgren & Lawrence grade III or IV) compared with 23 of 465 (4.9%) uninjured ACL-intact contralateral knees. After ACL injury, irrespective of whether the patients were treated operatively or nonoperatively, the relative risk (RR) of developing even minimal osteoarthritis was 3.89 (P < .00001), while the RR of developing moderate to severe osteoarthritis (grade III and IV) was 3.84 (P < .0004). Nonoperatively treated ACL-injured knees had significantly higher RR (RR, 4.98; P < .00001) of developing any grade of osteoarthritis compared with those treated with reconstructive surgery (RR, 3.62; P < .00001). Investigation of progression to moderate or severe osteoarthritis (grade III or IV only) after 10 years showed that ACL-reconstructed knees had a significantly higher RR (RR, 4.71; P < .00001) compared with nonoperative management (RR, 2.41; P = .54). It was not possible to stratify for return to sports among the patients undergoing ACL reconstruction. CONCLUSION: Results support the proposition that ACL injury predisposes knees to osteoarthritis, while ACL reconstruction surgery has a role in reducing the risk of developing degenerative changes at 10 years. However, returning to sports activities after ligament reconstruction may exacerbate the development of arthritis. PMID- 24214930 TI - Meniscus allograft transplantation: a comparison of medial and lateral procedures. AB - BACKGROUND: Because of the anatomic and biomechanical differences between the lateral and medial menisci, it is believed that the indications, combined injuries, techniques, and outcomes of the 2 meniscus allograft transplantation (MAT) procedures may be different. HYPOTHESIS: Medial meniscus transplantation (medial group) usually combines concomitant surgeries, such as anterior cruciate ligament (ACL) reconstruction, so the medial group will have worse clinical results than the lateral group (lateral meniscus transplantation). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was conducted on 91 patients who underwent MAT (lateral group, n = 56; medial group, n = 35). There were 33 patients with an absence of a concurrent injury (isolated group) and 58 patients with the presence of a concurrent injury (combined group). The mean follow-up was 40 months (range, 24-125 months). Clinical outcomes for range of motion (ROM), visual analog scale (VAS) for pain score, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and Tegner activity score were evaluated, and an objective evaluation was performed using magnetic resonance imaging (MRI) and second-look arthroscopic surgery. RESULTS: At final follow-up, the mean results for ROM, VAS score, IKDC subjective score, Lysholm score, Tegner activity score, and patient subjective satisfaction were not statistically different between the lateral and medial groups (P > .05). The VAS and Lysholm scores of the isolated group were significantly better than those of the combined group. Follow-up MRI was performed on 35 patients (24 in the lateral group and 11 in the medial group). Mean graft extrusion was 1.7 mm in the lateral group and 2.6 mm in the medial group (P = .075). The relative percentage of extrusion was 19.4% in the lateral group and 32.0% in the medial group (P = .011). Anterior cruciate ligament reconstruction occurred more commonly in the medial group, and cartilage procedures occurred more commonly in the lateral group. CONCLUSION: The clinical results of the lateral group were not different from those of the medial group. More graft extrusion was found in the medial group on MRI, and second-look arthroscopic surgery results of the lateral group were not as good as those of the medial group. The VAS and Lysholm scores of the combined group were worse than those of the isolated group. With regard to concomitant surgery, ACL reconstruction was most common in the medial group and cartilage procedures in the lateral group. PMID- 24214931 TI - The reliability and validity of the MATRICS functional assessment battery. AB - OBJECTIVES: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was designed to encourage the development of cognitive enhancing agents for schizophrenia. For a medication to receive this indication, regulatory agencies require evidence of improvement in both cognition and functional outcome. Functional capacity measures typically used in clinical trials as intermediate measures of functional outcome must be adapted to fit different cultural contexts for use internationally. We examined the psychometric properties of the MATRICS Functional Assessment Battery (MFAB), comprised of 2 subtests from the UCSD Performance-based Skills Assessment (UPSA) and one from the Test of Adaptive Behavior in Schizophrenia (TABS) that were rated by experts in a previous study to be the most appropriate functional capacity assessments across different cultural contexts. METHOD: Four sites in India administered the MFAB, a brief version of the UPSA, the MATRICS Cognitive Consensus Battery, measures of symptomatology, and a measure of global functional outcome to 141 individuals with schizophrenia at a baseline assessment and at 4 weeks later. RESULTS: Test-retest reliability based on the intraclass correlation coefficient was significantly better for the UCSD Performance-Based Skills Assessment-Brief (UPSA-B). Pearson correlation coefficients over time were not significantly different for the 2 measures. Only the MFAB was significantly correlated with functional outcome as measured by the Specific Levels of Functioning Scale. CONCLUSIONS: The psychometric properties of the MFAB and UPSA-B were similar. The MATRICS scientific board chose to translate the MFAB into multiple languages for potential use in studies of novel medications seeking an indication for improving cognition in schizophrenia. PMID- 24214932 TI - Identifying cognitive remediation change through computational modelling--effects on reinforcement learning in schizophrenia. AB - OBJECTIVE: Converging research suggests that individuals with schizophrenia show a marked impairment in reinforcement learning, particularly in tasks requiring flexibility and adaptation. The problem has been associated with dopamine reward systems. This study explores, for the first time, the characteristics of this impairment and how it is affected by a behavioral intervention-cognitive remediation. METHOD: Using computational modelling, 3 reinforcement learning parameters based on the Wisconsin Card Sorting Test (WCST) trial-by-trial performance were estimated: R (reward sensitivity), P (punishment sensitivity), and D (choice consistency). In Study 1 the parameters were compared between a group of individuals with schizophrenia (n = 100) and a healthy control group (n = 50). In Study 2 the effect of cognitive remediation therapy (CRT) on these parameters was assessed in 2 groups of individuals with schizophrenia, one receiving CRT (n = 37) and the other receiving treatment as usual (TAU, n = 34). RESULTS: In Study 1 individuals with schizophrenia showed impairment in the R and P parameters compared with healthy controls. Study 2 demonstrated that sensitivity to negative feedback (P) and reward (R) improved in the CRT group after therapy compared with the TAU group. R and P parameter change correlated with WCST outputs. Improvements in R and P after CRT were associated with working memory gains and reduction of negative symptoms, respectively. CONCLUSION: Schizophrenia reinforcement learning difficulties negatively influence performance in shift learning tasks. CRT can improve sensitivity to reward and punishment. Identifying parameters that show change may be useful in experimental medicine studies to identify cognitive domains susceptible to improvement. PMID- 24214933 TI - Reduced mirror neuron activity in schizophrenia and its association with theory of mind deficits: evidence from a transcranial magnetic stimulation study. AB - BACKGROUND: The "mirror-neuron system" has been proposed to be a neurophysiological substrate for social cognition (SC) ability. We used transcranial magnetic stimulation (TMS) paradigms to compare putative mirror neuron activity (MNA) in 3 groups: antipsychotic-naive, medicated schizophrenia patients, and healthy comparison subjects. We also explored the association between MNA and SC ability in patients. METHODS: Fifty-four consenting right handed schizophrenia patients (33 antipsychotic naive) and 45 matched healthy comparison subjects completed a TMS experiment to assess putative premotor MNA. We used 4 TMS paradigms of eliciting motor-evoked potentials (MEP) in the right first dorsal interosseous (FDI) muscle. These were applied while the subjects observed a goal-directed action involving the FDI (actual action and its video) and a static image. The difference in the amplitude of the MEP while they observed the static image and the action provided a measure of MNA. Subjects also underwent SC assessments (theory of mind [ToM], emotion processing, and social perception). RESULTS: Two-way repeated measures ANOVA revealed significant group * occasion interaction effect in 3 TMS paradigms, indicating deficient motor facilitation during action observation relative to rest state in antipsychotic naive schizophrenia patients as compared with the other two groups. Among patients, there were significant direct correlations between measures of MNA and ToM performance. CONCLUSIONS: Antipsychotic-naive schizophrenia patients have poorer MNA than medicated patients and healthy controls. Measures of putative MNA had significant and consistent associations with ToM abilities. These findings suggest a possibility of deficient mirror neuron system underlying SC deficits in schizophrenia. PMID- 24214934 TI - No evidence for local adaptation in an invasive alien plant: field and greenhouse experiments tracing a colonization sequence. AB - BACKGROUND AND AIMS: Local adaptation enables plant species to persist under different environmental conditions. Evolutionary change can occur rapidly in invasive annual species and has been shown to lead to local adaptation. However, the patterns and mechanisms of local adaptation in invasive species along colonization sequences are not yet understood. Thus, in this study the alien annual Impatiens glandulifera was used to investigate local adaptation to distinct habitats that have been consecutively invaded in central Europe. METHODS: A reciprocal transplant experiment was performed using 15 populations from alluvial deciduous forests, fallow meadows and coniferous upland forests, and a greenhouse experiment was performed in which plants from these habitats were grown under treatments reflecting the main habitat differentiators (shade, soil acidity, competition). KEY RESULTS: Biomass production, specific leaf area, plant height and relative growth rate differed between habitats in the field experiment and between treatments in the greenhouse, but not between seed origins. Overall, there was no indication of local adaptation in either experiment. CONCLUSIONS: Since I. glandulifera is a successful invader in many habitats without showing local adaptation, it is suggested that the species is coping with environmental variation by means of high phenotypic plasticity. The species seems to follow a 'jack-and-master' strategy, i.e. it is able to maintain high fitness under a wide range of environmental conditions, but performs particularly well in favourable habitats. Therefore, the proposed colonization sequence is likely to be based primarily on changes in propagule pressure. It is concluded that invasive alien plants can become dominant in distinct habitats without local adaptation. PMID- 24214935 TI - Wound healing during a heat wave. PMID- 24214936 TI - Returning to ourselves: Palestinian complementary healers in Israel. AB - Studies of traditional healers in various cultures describe their initiation into the healing profession as a climax that constructs their professional and personal identity. Literature emphasizes the healers' intense association with the culture in which they work, as reflected in the initiation narratives that healers in various cultures recount. In this article we reveal unique initiation stories and identity formation from Palestinian nonconventional healers in Israel who described a cross-cultural journey: After studying healing traditions of foreign cultures and on returning to their own cultural environment, they developed a unique and complex combination of healing values and traditions. We examine the stories of these healers, whose personal and professional identities are affected by cultural, political, and social contexts. We note the blending of healing traditions and practices, and the changes in identity, assessing them against cultural processes that many Palestinians in Israel have been undergoing over the past few decades. PMID- 24214939 TI - Predictors of recurrent appendicitis after non-operative management of children with perforated appendicitis presenting with an appendicular inflammatory mass. AB - AIM: To determine clinical and imaging predictors of recurrent appendicitis after non-operative management for children with perforated appendicitis presenting with an appendicular inflammatory mass. METHODS: A case-control study was carried out of children with clinical and ultrasonographic diagnosis of an appendicular inflammatory mass. Patients were divided into two groups according to the presence or not of recurrent appendicitis (or predisposing pathological findings during interval appendectomy). Several clinical and imaging factors were compared between both groups using an independent and progressive analysis to identify which were the most relevant predictors. RESULTS: The persistence of symptoms after resolution of the appendicular inflammatory mass, as well as its time of resolution (p<0.001), were the most relevant factors during group classification. The identification of an ultrasonographic image of an appendicolith and the initial size of the mass were also identified as independent predictors (p<0.018 and p<0.01). The presence of the first two factors in a patient was strongly associated with recurrent appendicitis. CONCLUSIONS: Persistent symptoms after the recovery of the initial episode, associated with a slow resolution of the appendicular inflammatory mass, are indications for an interval appendectomy. A previous history of appendicitis or detection of an ultrasonographic image of an appendicolith is the other indication for an interval appendectomy. PMID- 24214940 TI - Meeting the physical health needs of our looked after children. PMID- 24214941 TI - Geranylgeranyl reductase and ferredoxin from Methanosarcina acetivorans are required for the synthesis of fully reduced archaeal membrane lipid in Escherichia coli cells. AB - Archaea produce membrane lipids that typically possess fully saturated isoprenoid hydrocarbon chains attached to the glycerol moiety via ether bonds. They are functionally similar to, but structurally and biosynthetically distinct from, the fatty acid-based membrane lipids of bacteria and eukaryotes. It is believed that the characteristic lipid structure helps archaea survive under severe conditions such as extremely low or high pH, high salt concentrations, and/or high temperatures. We detail here the first successful production of an intact archaeal membrane lipid, which has fully saturated isoprenoid chains, in bacterial cells. The introduction of six phospholipid biosynthetic genes from a methanogenic archaeon, Methanosarcina acetivorans, in Escherichia coli enabled the host bacterium to synthesize the archaeal lipid, i.e., diphytanylglyceryl phosphoglycerol, while a glycerol modification of the phosphate group was probably catalyzed by endogenous E. coli enzymes. Reduction of the isoprenoid chains occurred only when archaeal ferredoxin was expressed with geranylgeranyl reductase, suggesting the role of ferredoxin as a specific electron donor for the reductase. This report is the first identification of a physiological reducer for archaeal geranylgeranyl reductase. On the other hand, geranylgeranyl reductase from the thermoacidophilic archaeon Sulfolobus acidocaldarius could, by itself, replace both its orthologue and ferredoxin from M. acetivorans, which indicated that an endogenous redox system of E. coli reduced the enzyme. PMID- 24214942 TI - Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease. AB - The Bacillus anthracis secretome includes protective antigen, lethal factor, and edema factor, which are the components of anthrax toxin, and other proteins with known or potential roles in anthrax disease. Immune inhibitor A1 (InhA1) is a secreted metalloprotease that is unique to pathogenic members of the Bacillus genus and has been associated with cleavage of host proteins during infection. Here, we report the effect of InhA1 on the B. anthracis secretome. Differential in-gel electrophoresis of proteins present in culture supernatants from a parent strain and an isogenic inhA1-null mutant revealed multiple differences. Of the 1,340 protein spots observed, approximately one-third were less abundant and one third were more abundant in the inhA1 secretome than in the parent strain secretome. Proteases were strongly represented among those proteins exhibiting a 9-fold or greater change. InhA1 purified from a B. anthracis culture supernatant directly cleaved each of the anthrax toxin proteins as well as an additional secreted protease, Npr599. The conserved zinc binding motif HEXXH of InhA1 (HEYGH) was critical for its proteolytic activity. Our data reveal that InhA1 directly and indirectly modulates the form and/or abundance of over half of all the secreted proteins of B. anthracis. The proteolytic activity of InhA1 on established secreted virulence factors, additional proteases, and other secreted proteins suggests that this major protease plays an important role in virulence not only by cleaving mammalian substrates but also by modulating the B. anthracis secretome itself. PMID- 24214943 TI - The twin arginine translocation system is essential for aerobic growth and full virulence of Burkholderia thailandensis. AB - The twin arginine translocation (Tat) system in bacteria is responsible for transporting folded proteins across the cytoplasmic membrane, and in some bacteria, Tat-exported substrates have been linked to virulence. We report here that the Tat machinery is present in Burkholderia pseudomallei, B. mallei, and B. thailandensis, and we show that the system is essential for aerobic but not anaerobic growth. Switching off of the Tat system in B. thailandensis grown anaerobically resulted in filamentous bacteria, and bacteria showed increased sensitivity to some beta-lactam antibiotics. In Galleria mellonella and zebrafish infection models, the Tat conditional mutant was attenuated. The aerobic growth restricted phenotype indicates that Tat substrates may play a functional role in oxygen-dependent energy conservation. In other bacteria, aerobic growth restriction in Tat mutants has been attributed to the inability to translocate PetA, the Rieske iron-sulfur protein which forms part of the quinol-cytochrome c oxidoreductase complex. Here, we show that PetA is not responsible for aerobic growth restriction in B. thailandensis. However, we have identified an operon encoding 2 proteins of unknown function (BTH_I2176 and BTH_I2175) that play a role in aerobic growth restriction, and we present evidence that BTH_I2176 is Tat translocated. PMID- 24214944 TI - Characterization of novel virulent broad-host-range phages of Xylella fastidiosa and Xanthomonas. AB - The xylem-limited bacterium Xylella fastidiosa is the causal agent of several plant diseases, most notably Pierce's disease of grape and citrus variegated chlorosis. We report the isolation and characterization of the first virulent phages for X. fastidiosa, siphophages Sano and Salvo and podophages Prado and Paz, with a host range that includes Xanthomonas spp. Phages propagated on homologous hosts had observed adsorption rate constants of ~4 * 10(-12) ml cell( 1) min(-1) for X. fastidiosa strain Temecula 1 and ~5 * 10(-10) to 7 * 10(-10) ml cell(-1) min(-1) for Xanthomonas strain EC-12. Sano and Salvo exhibit >80% nucleotide identity to each other in aligned regions and are syntenic to phage BcepNazgul. We propose that phage BcepNazgul is the founding member of a novel phage type, to which Sano and Salvo belong. The lysis genes of the Nazgul-like phage type include a gene that encodes an outer membrane lipoprotein endolysin and also spanin gene families that provide insight into the evolution of the lysis pathway for phages of Gram-negative hosts. Prado and Paz, although exhibiting no significant DNA homology to each other, are new members of the phiKMV-like phage type, based on the position of the single-subunit RNA polymerase gene. The four phages are type IV pilus dependent for infection of both X. fastidiosa and Xanthomonas. The phages may be useful as agents for an effective and environmentally responsible strategy for the control of diseases caused by X. fastidiosa. PMID- 24214945 TI - Protection from oxidative stress relies mainly on derepression of OxyR-dependent KatB and Dps in Shewanella oneidensis. AB - Shewanella thrives in redox-stratified environments where accumulation of H2O2 becomes inevitable because of the chemical oxidation of reduced metals, sulfur species, or organic molecules. As a research model, the representative species Shewanella oneidensis has been extensively studied for its response to various stresses. However, little progress has been made toward an understanding of the physiological and genetic responses of this bacterium to oxidative stress, which is critically relevant to its application as a dissimilatory metal-reducing bacterium. In this study, we systematically investigated the mechanism underlying the response to H2O2 at cellular, genomic, and molecular levels. Using transcriptional profiling, we found that S. oneidensis is hypersensitive to H2O2 in comparison with Escherichia coli, and well-conserved defense genes such as ahpCF, katB, katG, and dps appear to form the first line of defense, whereas iron sulfur-protecting proteins may not play a significant role. Subsequent identification and characterization of an analogue of the E. coli oxyR gene revealed that S. oneidensis OxyR is the master regulator that mediates the bacterial response to H2O2-induced oxidative stress by directly repressing or activating the defense genes. The sensitivity of S. oneidensis to H2O2 is likely attributable to the lack of an inducible manganese import mechanism during stress. To cope with stress, major strategies that S. oneidensis adopts include rapid removal of the oxidant and restriction of intracellular iron concentrations, both of which are achieved predominantly by derepression of the katB and dps genes. PMID- 24214946 TI - Enteric YaiW is a surface-exposed outer membrane lipoprotein that affects sensitivity to an antimicrobial peptide. AB - yaiW is a previously uncharacterized gene found in enteric bacteria that is of particular interest because it is located adjacent to the sbmA gene, whose bacA ortholog is required for Sinorhizobium meliloti symbiosis and Brucella abortus pathogenesis. We show that yaiW is cotranscribed with sbmA in Escherichia coli and Salmonella enterica serovar Typhi and Typhimurium strains. We present evidence that the YaiW is a palmitate-modified surface exposed outer membrane lipoprotein. Since BacA function affects the very-long-chain fatty acid (VLCFA) modification of S. meliloti and B. abortus lipid A, we tested whether SbmA function might affect either the fatty acid modification of the YaiW lipoprotein or the fatty acid modification of enteric lipid A but found that it did not. Interestingly, we did observe that E. coli SbmA suppresses deficiencies in the VLCFA modification of the lipopolysaccharide of an S. meliloti bacA mutant despite the absence of VLCFA in E. coli. Finally, we found that both YaiW and SbmA positively affect the uptake of proline-rich Bac7 peptides, suggesting a possible connection between their cellular functions. PMID- 24214947 TI - Biochemical and biophysical characterization of the two isoforms of cbb3-type cytochrome c oxidase from Pseudomonas stutzeri. AB - The cbb3-type cytochrome c oxidases (cbb3-CcOs) are members of the heme-copper oxidase superfamily that couple the reduction of oxygen to translocation of protons across the membrane. The cbb3-CcOs are present only in bacteria and play a primary role in microaerobic respiration, being essential for nitrogen-fixing endosymbionts and for some human pathogens. As frequently observed in Pseudomonads, Pseudomonas stutzeri contains two independent ccoNO(Q)P operons encoding the two cbb3 isoforms, Cbb3-1 and Cbb3-2. While the crystal structure of Cbb3-1 from P. stutzeri was determined recently and cbb3-CcOs from other organisms were characterized functionally, less emphasis has been placed on the isoform-specific differences between the cbb3-CcOs. In this work, both isoforms were homologously expressed in P. stutzeri strains from which the genomic version of the respective operon was deleted. We purified both cbb3 isoforms separately by affinity chromatography and increased the yield of Cbb3-2 to a similar level as Cbb3-1 by replacing its native promoter. Mass spectrometry, UV-visible (UV Vis) spectroscopy, differential scanning calorimetry, as well as oxygen reductase and catalase activity measurements were employed to characterize both cbb3 isoforms. Differences were found concerning the thermal stability and the presence of subunit CcoQ. However, no significant differences between the two isoforms were observed otherwise. Interestingly, a surprisingly high turnover of at least 2,000 electrons s(-1) and a high Michaelis-Menten constant (Km ~ 3.6 mM) using ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD) as the electron donor were characteristic for both P. stutzeri cbb3-CcOs. Our work provides the basis for further mutagenesis studies of each of the two cbb3 isoforms specifically. PMID- 24214948 TI - Simultaneous involvement of a tungsten-containing aldehyde:ferredoxin oxidoreductase and a phenylacetaldehyde dehydrogenase in anaerobic phenylalanine metabolism. AB - Anaerobic phenylalanine metabolism in the denitrifying betaproteobacterium Aromatoleum aromaticum is initiated by conversion of phenylalanine to phenylacetate, which is further metabolized via benzoyl-coenzyme A (CoA). The formation of phenylacetate is catalyzed by phenylalanine transaminase, phenylpyruvate decarboxylase, and a phenylacetaldehyde-oxidizing enzyme. The presence of these enzymes was detected in extracts of cells grown with phenylalanine and nitrate. We found that two distinct enzymes are involved in the oxidation of phenylacetaldehyde to phenylacetate, an aldehyde:ferredoxin oxidoreductase (AOR) and a phenylacetaldehyde dehydrogenase (PDH). Based on sequence comparison, growth studies with various tungstate concentrations, and metal analysis of the enriched enzyme, AOR was shown to be a tungsten-containing enzyme, necessitating specific cofactor biosynthetic pathways for molybdenum- and tungsten-dependent enzymes simultaneously. We predict from the genome sequence that most enzymes of molybdopterin biosynthesis are shared, while the molybdate/tungstate uptake systems are duplicated and specialized paralogs of the sulfur-inserting MoaD and the metal-inserting MoeA proteins seem to be involved in dedicating biosynthesis toward molybdenum or tungsten cofactors. We also characterized PDH biochemically and identified both NAD(+) and NADP(+) as electron acceptors. We identified the gene coding for the enzyme and purified a recombinant Strep-tagged PDH variant. The homotetrameric enzyme is highly specific for phenylacetaldehyde, has cooperative kinetics toward the substrate, and shows considerable substrate inhibition. Our data suggest that A. aromaticum utilizes PDH as the primary enzyme during anaerobic phenylalanine degradation, whereas AOR is not essential for the metabolic pathway. We hypothesize a function as a detoxifying enzyme if high aldehyde concentrations accumulate in the cytoplasm, which would lead to substrate inhibition of PDH. PMID- 24214949 TI - The ResD response regulator, through functional interaction with NsrR and fur, plays three distinct roles in Bacillus subtilis transcriptional control. AB - The ResD response regulator activates transcription of diverse genes in Bacillus subtilis in response to oxygen limitation. ResD regulon genes that are the most highly induced during nitrate respiration include the nitrite reductase operon (nasDEF) and the flavohemoglobin gene (hmp), whose products function in nitric oxide (NO) metabolism. Transcription of these genes is also under the negative control of the NO-sensitive NsrR repressor. Recent studies showed that the NsrR regulon contains genes with no apparent relevance to NO metabolism and that the ResD response regulator and NsrR coordinately regulate transcription. To determine whether these genes are direct targets of NsrR and ResD, we used chromatin affinity precipitation coupled with tiling chip (ChAP-chip) and ChAP followed by quantitative PCR (ChAP-qPCR) analyses. The study showed that ResD and NsrR directly control transcription of the ykuNOP operon in the Fur regulon. ResD functions as an activator at the nasD and hmp promoters, whereas it functions at the ykuN promoter as an antirepressor of Fur and a corepressor for NsrR. This mechanism likely participates in fine-tuning of transcript levels in response to different sources of stress, such as oxygen limitation, iron limitation, and exposure to NO. PMID- 24214950 TI - Use of abdominal field block injections with liposomal bupivicaine to control postoperative pain after abdominoplasty. AB - BACKGROUND: It is well known that improving postoperative pain control in plastic surgery procedures leads to earlier mobilization, shortened hospital stay, reduced hospital costs, and increased patient satisfaction. OBJECTIVE: The authors evaluate the use of abdominal field block injections with liposomal bupivicaine (Exparel; Pacira Pharmaceuticals, Inc, San Diego, California) in postoperative pain management in patients undergoing abdominoplasty with rectus plication. METHODS: Case records from 64 female patients who underwent abdominoplasty with rectus plication were reviewed. We performed a total of 118 abdominoplasties with rectus plication, alone or in combination with other surgical procedures, from August 2012 to December 2012, but 54 patients were excluded from the series due to inadequate follow-up. Patients received liposomal bupivicaine injections in an abdominal field block fashion. Patient age, height, weight, and smoking status were recorded. Delivery of standardized postoperative intramuscular or intravenous injections and oral pain pills was recorded. Postoperative data and questionnaires were used to evaluate clinical efficacy. RESULTS: The average number of procedures (including abdominoplasty with rectus plication) per patient was 7. Average patient body mass index was 27 kg/m(2). Average pain scores were 3.5 (postoperative visit 1) and 2.8 (visit 2). The average number of oral pain pills required was 14 at the first postoperative visit and 11.5 at the second postoperative visit. Patients were able to resume normal activity at an average of 6.4 days. CONCLUSIONS: Our experience with liposomal bupivicaine injections for regional blocks in abdominoplasty with rectus plication indicates that patients experienced reduced postoperative pain, required less postoperative narcotic medication, and resumed both earlier ambulation and normal activity. Further investigation is warranted with more clinical cases to recommend the use of this medication for routine pain management after an abdominoplasty. PMID- 24214951 TI - The impact of body mass index on reduction mammaplasty: a multicenter analysis of 2492 patients. AB - BACKGROUND: Reduction mammaplasty is commonly performed in women who are considered obese by the body mass index (BMI) classification of the World Health Organization. OBJECTIVES: The authors compare complication rates among breast reduction patients, stratified by BMI, across multiple institutions. METHODS: A retrospective analysis was performed of all reduction mammaplasties in the database of the National Surgical Quality Improvement Program for 2006 through 2010. Demographic, comorbidity, and BMI data were collected. Data on medical and surgical complications, reoperation, and mortality were collected through 30 days postsurgery. RESULTS: Of 2492 patients, 55% were considered obese (BMI >30). The overall rate of surgical complications was 4.0%, increasing from 2.4% for BMI <25 to 7.1% for BMI >45 (P = .006), with an adjusted odds ratio of 2.97 for BMI >45 versus BMI <25. The most common surgical complication was superficial surgical site infection; it was found in 2.9% of patients, increasing from 2.1% for BMI <25 to 5.1% for BMI >45 (P = .03). The medical complication rate was 0.6%, and the reoperation rate was 2.1%. There were no deaths. A maximal point analysis showed that BMI >=39 was associated with a significantly higher complication rate, with an odds ratio of 2.38. CONCLUSIONS: Reduction mammaplasty is a safe surgical procedure, even when performed on obese patients. However, patients with higher BMI have a greater risk of surgical site complications. This risk should be discussed preoperatively with obese patients. PMID- 24214952 TI - Association of variant rs7903146 (C/T) single nucleotide polymorphism of TCF7L2 gene with impairment in wound healing among north Indian type 2 diabetes population: a case-control study. AB - The variants of transcription factor 7-like 2 (TCF7L2) gene have been shown to be associated with type 2 diabetes mellitus (T2DM) and its several secondary complications. Here, we aimed to examine the possible role of one of the common variant of this gene, rs7903146 (C/T), with impairment of wound healing in cases with T2DM. A total of 750 individuals, including 322 patients with T2DM and 120 patients with diabetic foot ulcers (DFUs) and 308 controls, were analyzed for rs7903146 variant of the TCF7L2 gene. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. For rs7903146 variant, TT genotype frequency in patients with DFU was 10.8% and in controls was 5.2%. Risk genotype (TT) frequencies showed statistically significant difference between the DFU patients versus non-DM control group (odds ratio = 2.44, P = .037, 95% confidence interval = 1.05-5.64) compared with nonrisk genotype (CC + CT). In the present study, a positive significant association between DFU and the TT genotype of rs7903146 (C/T) variant of TCF7L2 gene was found. PMID- 24214953 TI - Squamous cell carcinoma and ledderhose disease: a case report. AB - Ledderhose disease is disorder of the plantar aponeurosis. This disease is not so common and can be tackled with a surgical or conservative approach. A case of a 73-year-old man came to our attention who had a 26-year history of painless bilateral plantar nodules coalescing into an indurated mass. An ulcerative nodule had been noted in the last 16 months on the right foot, in the absence of trauma, not responsive to conservative treatment, so we decided to perform a biopsy. The histopatologic examination showed squamous cell carcinoma, with warty, well differentiated, low-grade malignancy. Surgical treatment was suggested, so, in pneumoischemia, we made a surgical incision including the skin lesion. Then we proceeded to sculpture the anterolateral thigh fasciacutaneous flap to obtain adequate soft tissue coverage. The tumor was completely removed. Current reconstructive possibilities comprise a good anatomofunctional recovery even in the case of large demolition requests for the therapy of advanced cases of the disease described in this article. Correlation between Ledderhose disease and the formation of malignant tumors has not been made as yet, but perhaps an element that could unite these pathologies can be researched in the lively cell proliferation that characterizes both. It would be interesting to analyze the biological substrate, as well as the systemic and local levels, in patients where both diseases are manifested. PMID- 24214954 TI - A case of fatal necrotizing fasciitis arising from chronic lymphedema. AB - Chronic lymphedema and lymphangitis are common adverse effects following treatment for gynecological cancer. Because the early symptoms of necrotizing fasciitis are similar to those of lymphangitis, fatal outcome can occur if patients or physicians underestimate this condition. Here, we present a case of necrotizing fasciitis in a patient with chronic lymphedema. PMID- 24214955 TI - TFBSshape: a motif database for DNA shape features of transcription factor binding sites. AB - Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors (TFs), proteins recognize DNA as a three-dimensional object. DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein-DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone. PMID- 24214956 TI - Distinct substrate specificities of Arabidopsis DCL3 and DCL4. AB - In Arabidopsis thaliana, Dicer-like 3 (DCL3) and Dicer-like 4 (DCL4) cleave long, perfect double-stranded RNAs (dsRNAs) into 24 and 21 nucleotides (nt) small interfering RNAs, respectively, which in turn function in RNA-directed DNA methylation and RNA interference, respectively. To reveal how DCL3 and DCL4 individually recognize long perfect dsRNAs as substrates, we biochemically characterized DCL3 and DCL4 and compared their enzymatic properties. DCL3 preferentially cleaves short dsRNAs with 5' phosphorylated adenosine or uridine and a 1 nt 3' overhang, whereas DCL4 cleaves long dsRNAs with blunt ends or with a 1 or 2 nt 3' overhang with similar efficiency. DCL3 produces 24 nt RNA duplexes with 2 nt 3' overhangs by the 5' counting rule. Inorganic phosphate, NaCl and KCl enhance DCL3 activity but inhibit DCL4 activity. These results indicate that plants use DCLs with distinct catalytic profiles to ensure each dsRNA substrate generates only a specific length of siRNAs that trigger a unique siRNA-mediated response. PMID- 24214957 TI - bNAber: database of broadly neutralizing HIV antibodies. AB - The discovery of broadly neutralizing antibodies (bNAbs) has provided an enormous impetus to the HIV vaccine research and to entire immunology. The bNAber database at http://bNAber.org provides open, user-friendly access to detailed data on the rapidly growing list of HIV bNAbs, including neutralization profiles, sequences and three-dimensional structures (when available). It also provides an extensive list of visualization and analysis tools, such as heatmaps to analyse neutralization data as well as structure and sequence viewers to correlate bNAbs properties with structural and sequence features of individual antibodies. The goal of the bNAber database is to enable researchers in this field to easily compare and analyse available information on bNAbs thereby supporting efforts to design an effective vaccine for HIV/AIDS. The bNAber database not only provides easy access to data that currently is scattered in the Supplementary Materials sections of individual papers, but also contributes to the development of general standards of data that have to be presented with the discovery of new bNAbs and a universal mechanism of how such data can be shared. PMID- 24214959 TI - BacDive--the Bacterial Diversity Metadatabase. AB - BacDive-the Bacterial Diversity Metadatabase (http://bacdive.dsmz.de) merges detailed strain-linked information on the different aspects of bacterial and archaeal biodiversity. Currently (release 9/2013), BacDive contains entries for 23 458 strains and provides information on their taxonomy, morphology, physiology, sampling and concomitant environmental conditions as well as molecular biology. Where available, links to access the respective biological resources are given. The majority of the BacDive data is manually annotated and curated. The BacDive portal offers an easy-to-use simple search and in addition powerful advanced search functionalities allowing to combine more than 30 search fields for text and numerical data. The user can compile individual sets of strains to a download selection that can easily be imported into nearly all spreadsheet applications. PMID- 24214958 TI - Comparative analysis of affinity-based 5-hydroxymethylation enrichment techniques. AB - The epigenetic modification of 5-hydroxymethylcytosine (5hmC) is receiving great attention due to its potential role in DNA methylation reprogramming and as a cell state identifier. Given this interest, it is important to identify reliable and cost-effective methods for the enrichment of 5hmC marked DNA for downstream analysis. We tested three commonly used affinity-based enrichment techniques; (i) antibody, (ii) chemical capture and (iii) protein affinity enrichment and assessed their ability to accurately and reproducibly report 5hmC profiles in mouse tissues containing high (brain) and lower (liver) levels of 5hmC. The protein-affinity technique is a poor reporter of 5hmC profiles, delivering 5hmC patterns that are incompatible with other methods. Both antibody and chemical capture-based techniques generate highly similar genome-wide patterns for 5hmC, which are independently validated by standard quantitative PCR (qPCR) and glucosyl-sensitive restriction enzyme digestion (gRES-qPCR). Both antibody and chemical capture generated profiles reproducibly link to unique chromatin modification profiles associated with 5hmC. However, there appears to be a slight bias of the antibody to bind to regions of DNA rich in simple repeats. Ultimately, the increased specificity observed with chemical capture-based approaches makes this an attractive method for the analysis of locus-specific or genome-wide patterns of 5hmC. PMID- 24214960 TI - High-resolution microbial community reconstruction by integrating short reads from multiple 16S rRNA regions. AB - The emergence of massively parallel sequencing technology has revolutionized microbial profiling, allowing the unprecedented comparison of microbial diversity across time and space in a wide range of host-associated and environmental ecosystems. Although the high-throughput nature of such methods enables the detection of low-frequency bacteria, these advances come at the cost of sequencing read length, limiting the phylogenetic resolution possible by current methods. Here, we present a generic approach for integrating short reads from large genomic regions, thus enabling phylogenetic resolution far exceeding current methods. The approach is based on a mapping to a statistical model that is later solved as a constrained optimization problem. We demonstrate the utility of this method by analyzing human saliva and Drosophila samples, using Illumina single-end sequencing of a 750 bp amplicon of the 16S rRNA gene. Phylogenetic resolution is significantly extended while reducing the number of falsely detected bacteria, as compared with standard single-region Roche 454 Pyrosequencing. Our approach can be seamlessly applied to simultaneous sequencing of multiple genes providing a higher resolution view of the composition and activity of complex microbial communities. PMID- 24214961 TI - Data, information, knowledge and principle: back to metabolism in KEGG. AB - In the hierarchy of data, information and knowledge, computational methods play a major role in the initial processing of data to extract information, but they alone become less effective to compile knowledge from information. The Kyoto Encyclopedia of Genes and Genomes (KEGG) resource (http://www.kegg.jp/ or http://www.genome.jp/kegg/) has been developed as a reference knowledge base to assist this latter process. In particular, the KEGG pathway maps are widely used for biological interpretation of genome sequences and other high-throughput data. The link from genomes to pathways is made through the KEGG Orthology system, a collection of manually defined ortholog groups identified by K numbers. To better automate this interpretation process the KEGG modules defined by Boolean expressions of K numbers have been expanded and improved. Once genes in a genome are annotated with K numbers, the KEGG modules can be computationally evaluated revealing metabolic capacities and other phenotypic features. The reaction modules, which represent chemical units of reactions, have been used to analyze design principles of metabolic networks and also to improve the definition of K numbers and associated annotations. For translational bioinformatics, the KEGG MEDICUS resource has been developed by integrating drug labels (package inserts) used in society. PMID- 24214962 TI - The eukaryotic linear motif resource ELM: 10 years and counting. AB - The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains ~200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways. PMID- 24214963 TI - Manually curated database of rice proteins. AB - 'Manually Curated Database of Rice Proteins' (MCDRP) available at http://www.genomeindia.org/biocuration is a unique curated database based on published experimental data. Semantic integration of scientific data is essential to gain a higher level of understanding of biological systems. Since the majority of scientific data is available as published literature, text mining is an essential step before the data can be integrated and made available for computer based search in various databases. However, text mining is a tedious exercise and thus, there is a large gap in the data available in curated databases and published literature. Moreover, data in an experiment can be perceived from several perspectives, which may not reflect in the text-based curation. In order to address such issues, we have demonstrated the feasibility of digitizing the experimental data itself by creating a database on rice proteins based on in house developed data curation models. Using these models data of individual experiments have been digitized with the help of universal ontologies. Currently, the database has data for over 1800 rice proteins curated from >4000 different experiments of over 400 research articles. Since every aspect of the experiment such as gene name, plant type, tissue and developmental stage has been digitized, experimental data can be rapidly accessed and integrated. PMID- 24214964 TI - DriverDB: an exome sequencing database for cancer driver gene identification. AB - Exome sequencing (exome-seq) has aided in the discovery of a huge amount of mutations in cancers, yet challenges remain in converting oncogenomics data into information that is interpretable and accessible for clinical care. We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification. We provide two points of view, 'Cancer' and 'Gene', to help researchers to visualize the relationships between cancers and driver genes/mutations. The 'Cancer' section summarizes the calculated results of driver genes by eight computational methods for a specific cancer type/dataset and provides three levels of biological interpretation for realization of the relationships between driver genes. The 'Gene' section is designed to visualize the mutation information of a driver gene in five different aspects. Moreover, a 'Meta-Analysis' function is provided so researchers may identify driver genes in customer-defined samples. The novel driver genes/mutations identified hold potential for both basic research and biotech applications. PMID- 24214965 TI - The ChEMBL bioactivity database: an update. AB - ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources and improvements in functionality have contributed to the growth and utility of the resource. In particular, more comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications; a new richer data model for representing drug targets has been developed; and a number of methods have been put in place to allow users to more easily identify reliable data. Finally, access to ChEMBL is now available via a new Resource Description Framework format, in addition to the web-based interface, data downloads and web services. PMID- 24214966 TI - DOOR 2.0: presenting operons and their functions through dynamic and integrated views. AB - We have recently developed a new version of the DOOR operon database, DOOR 2.0, which is available online at http://csbl.bmb.uga.edu/DOOR/ and will be updated on a regular basis. DOOR 2.0 contains genome-scale operons for 2072 prokaryotes with complete genomes, three times the number of genomes covered in the previous version published in 2009. DOOR 2.0 has a number of new features, compared with its previous version, including (i) more than 250,000 transcription units, experimentally validated or computationally predicted based on RNA-seq data, providing a dynamic functional view of the underlying operons; (ii) an integrated operon-centric data resource that provides not only operons for each covered genome but also their functional and regulatory information such as their cis regulatory binding sites for transcription initiation and termination, gene expression levels estimated based on RNA-seq data and conservation information across multiple genomes; (iii) a high-performance web service for online operon prediction on user-provided genomic sequences; (iv) an intuitive genome browser to support visualization of user-selected data; and (v) a keyword-based Google like search engine for finding the needed information intuitively and rapidly in this database. PMID- 24214967 TI - The mechanism of pseudouridine synthases from a covalent complex with RNA, and alternate specificity for U2605 versus U2604 between close homologs. AB - RluB catalyses the modification of U2605 to pseudouridine (Psi) in a stem-loop at the peptidyl transferase center of Escherichia coli 23S rRNA. The homolog RluF is specific to the adjacent nucleotide in the stem, U2604. The 1.3 A resolution crystal structure of the complex between the catalytic domain of RluB and the isolated substrate stem-loop, in which the target uridine is substituted by 5 fluorouridine (5-FU), reveals a covalent bond between the isomerized target base and tyrosine 140. The structure is compared with the catalytic domain alone determined at 2.5 A resolution. The RluB-bound stem-loop has essentially the same secondary structure as in the ribosome, with a bulge at A2602, but with 5-FU2605 flipped into the active site. We showed earlier that RluF induced a frame-shift of the RNA, moving A2602 into the stem and translating its target, U2604, into the active site. A hydrogen-bonding network stabilizes the bulge in the RluB-RNA but is not conserved in RluF and so RluF cannot stabilize the bulge. On the basis of the covalent bond between enzyme and isomerized 5-FU we propose a Michael addition mechanism for pseudouridine formation that is consistent with all experimental data. PMID- 24214968 TI - Deep sequencing of large library selections allows computational discovery of diverse sets of zinc fingers that bind common targets. AB - The Cys2His2 zinc finger (ZF) is the most frequently found sequence-specific DNA binding domain in eukaryotic proteins. The ZF's modular protein-DNA interface has also served as a platform for genome engineering applications. Despite decades of intense study, a predictive understanding of the DNA-binding specificities of either natural or engineered ZF domains remains elusive. To help fill this gap, we developed an integrated experimental-computational approach to enrich and recover distinct groups of ZFs that bind common targets. To showcase the power of our approach, we built several large ZF libraries and demonstrated their excellent diversity. As proof of principle, we used one of these ZF libraries to select and recover thousands of ZFs that bind several 3-nt targets of interest. We were then able to computationally cluster these recovered ZFs to reveal several distinct classes of proteins, all recovered from a single selection, to bind the same target. Finally, for each target studied, we confirmed that one or more representative ZFs yield the desired specificity. In sum, the described approach enables comprehensive large-scale selection and characterization of ZF specificities and should be a great aid in furthering our understanding of the ZF domain. PMID- 24214969 TI - Are There Executive Dysfunction Subtypes Within ADHD? AB - OBJECTIVE: Children with ADHD have heterogeneous behavioral and neuropsychological profiles. The aim of this study was to examine the possible utility of executive function (EF) subtypes within ADHD. METHOD: Participants were 357 children aged 6 through 13 with a diagnosis of ADHD. Children completed a brief laboratory battery measuring EF, including response inhibition, response variability, speed, and set-shifting. Children also completed standardized intelligence and achievement testing. RESULTS: Two-way cluster analysis of EF profiles of children with ADHD produced a three-cluster solution, labeled poor inhibitory control, poor set-shifting/speed, and intact task performance. Clusters significantly differed in measures of intelligence, academic achievement, and other disruptive behavior and anxiety/mood symptoms. CONCLUSION: These findings further support the idea that children with ADHD have heterogeneous EF profiles and suggest that the theory of ADHD should consider these individual differences in EF profiles within the ADHD diagnostic category. PMID- 24214970 TI - Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial. AB - OBJECTIVE: To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. METHOD: Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. RESULTS: Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = .270, p = .002) and DSM-IV inattention (r = -.343, p < .001). CONCLUSION: Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD. PMID- 24214971 TI - Cancerous inhibitor of protein phosphatase 2A (CIP2A) protein is involved in centrosome separation through the regulation of NIMA (never in mitosis gene A) related kinase 2 (NEK2) protein activity. AB - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in most human cancers and has been described as being involved in the progression of several human malignancies via the inhibition of protein phosphatase 2A (PP2A) activity toward c-Myc. However, with the exception of this role, the cellular function of CIP2A remains poorly understood. On the basis of yeast two-hybrid and coimmunoprecipitation assays, we demonstrate here that NIMA (never in mitosis gene A)-related kinase 2 (NEK2) is a binding partner for CIP2A. CIP2A exhibited dynamic changes in distribution, including the cytoplasm and centrosome, depending on the cell cycle stage. When CIP2A was depleted, centrosome separation and the mitotic spindle dynamics were impaired, resulting in the activation of spindle assembly checkpoint signaling and, ultimately, extension of the cell division time. Our data imply that CIP2A strongly interacts with NEK2 during G2/M phase, thereby enhancing NEK2 kinase activity to facilitate centrosome separation in a PP1- and PP2A-independent manner. In conclusion, CIP2A is involved in cell cycle progression through centrosome separation and mitotic spindle dynamics. PMID- 24214972 TI - Ceramides and glucosylceramides are independent antagonists of insulin signaling. AB - Inhibitors of sphingolipid synthesis protect mice from diet induced-insulin resistance, and sphingolipids such as ceramides and glucosylated-ceramides (e.g., GM3) are putative nutritional intermediates linking obesity to diabetes risk. Herein we investigated the role of each of these sphingolipids in muscle and adipose tissue and conclude that they are independent and separable antagonists of insulin signaling. Of particular note, ceramides antagonize insulin signaling in both myotubes and adipocytes, whereas glucosyceramides are only efficacious in adipocytes: 1) In myotubes exposed to saturated fats, inhibitors of enzymes required for ceramide synthesis enhance insulin signaling, but those targeting glucosylceramide synthase have no effect. 2) Exogenous ceramides antagonize insulin signaling in myotubes, whereas ganglioside precursors do not. 3) Overexpression of glucosylceramide synthase in myotubes induces glucosylceramide but enhances insulin signaling. In contrast, glucosylated ceramides have profound effects in adipocytes. For example, either ganglioside addition or human glucosylceramide synthase overexpression suppresses insulin signaling in adipocytes. These data have important mechanistic implications for understanding how these sphingolipids contribute to energy sensing and the disruption of anabolism under conditions of nutrient oversupply. PMID- 24214973 TI - Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins. AB - Tetra-cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2 (or -3 or -4) yl)porphyrins (ZnPs) with progressively increased lipophilicity were synthesized to investigate how the tri-dimensional shape and lipophilicity of the photosensitizer (PS) affect cellular uptake, subcellular distribution, and photodynamic efficacy. The effect of the tri-dimensional shape of the molecule was studied by shifting the N-alkyl substituent attached to the pyridyl nitrogen from ortho to meta and para positions. Progressive increase of lipophilicity from shorter hydrophilic (methyl) to longer amphiphilic (hexyl) alkyl chains increased the phototoxicity of the ZnP PSs. PS efficacy was also increased for all derivatives when the alkyl substituents were shifted from ortho to meta, and from meta to para positions. Both cellular uptake and subcellular distribution of the PSs were affected by the lipophilicity and the position of the alkyl chains on the periphery of the porphyrin ring. Whereas the hydrophilic ZnPs demonstrated mostly lysosomal distribution, the amphiphilic hexyl derivatives were associated with mitochondria, endoplasmic reticulum, and plasma membrane. A comparison of hexyl isomers revealed that cellular uptake and partition into membranes followed the order para > meta > ortho. Varying the position and length of the alkyl substituents affects (i) the exposure of cationic charges for electrostatic interactions with anionic biomolecules and (ii) the lipophilicity of the molecule. The charge, lipophilicity, and the tri-dimensional shape of the PS are the major factors that determine cellular uptake, subcellular distribution, and as a consequence, the phototoxicity of the PSs. PMID- 24214974 TI - Mutating a conserved proline residue within the trimerization domain modifies Na+ binding to excitatory amino acid transporters and associated conformational changes. AB - Excitatory amino acid transporters (EAATs) are crucial for glutamate homeostasis in the mammalian central nervous system. They are not only secondary active glutamate transporters but also function as anion channels, and different EAATs vary considerably in glutamate transport rates and associated anion current amplitudes. A naturally occurring mutation, which was identified in a patient with episodic ataxia type 6 and that predicts the substitution of a highly conserved proline at position 290 by arginine (P290R), was recently shown to reduce glutamate uptake and to increase anion conduction by hEAAT1. We here used voltage clamp fluorometry to define how the homologous P259R mutation modifies the functional properties of hEAAT3. P259R inverts the voltage dependence, changes the sodium dependence, and alters the time dependence of hEAAT3 fluorescence signals. Kinetic analysis of fluorescence signals indicate that P259R decelerates a conformational change associated with sodium binding to the glutamate-free mutant transporters. This alteration in the glutamate uptake cycle accounts for the experimentally observed changes in glutamate transport and anion conduction by P259R hEAAT3. PMID- 24214975 TI - Several cis-regulatory elements control mRNA stability, translation efficiency, and expression pattern of Prrxl1 (paired related homeobox protein-like 1). AB - The homeodomain transcription factor Prrxl1/DRG11 has emerged as a crucial molecule in the establishment of the pain circuitry, in particular spinal cord targeting of dorsal root ganglia (DRG) axons and differentiation of nociceptive glutamatergic spinal cord neurons. Despite Prrxl1 importance in the establishment of the DRG-spinal nociceptive circuit, the molecular mechanisms that regulate its expression along development remain largely unknown. Here, we show that Prrxl1 transcription is regulated by three alternative promoters (named P1, P2, and P3), which control the expression of three distinct Prrxl1 5'-UTR variants, named 5' UTR-A, 5'-UTR-B, and 5'-UTR-C. These 5'-UTR sequences confer distinct mRNA stability and translation efficiency to the Prrxl1 transcript. The most conserved promoter (P3) contains a TATA-box and displays in vivo enhancer activity in a pattern that overlaps with the zebrafish Prrxl1 homologue, drgx. Regulatory modules present in this sequence were identified and characterized, including a binding site for Phox2b. Concomitantly, we demonstrate that zebrafish Phox2b is required for the expression of drgx in the facial, glossopharyngeal, and vagal cranial ganglia. PMID- 24214976 TI - Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). AB - Umami taste perception in mammals is mediated by a heteromeric complex of two G protein-coupled receptors, T1R1 and T1R3. T1R1/T1R3 exhibits species-dependent differences in ligand specificity; human T1R1/T1R3 specifically responds to L Glu, whereas mouse T1R1/T1R3 responds more strongly to other L-amino acids than to L-Glu. The mechanism underlying this species difference remains unknown. In this study we analyzed chimeric human-mouse receptors and point mutants of T1R1/T1R3 and identified 12 key residues that modulate amino acid recognition in the human- and mouse-type responses in the extracellular Venus flytrap domain of T1R1. Molecular modeling revealed that the residues critical for human-type acidic amino acid recognition were located at the orthosteric ligand binding site. In contrast, all of the key residues for the mouse-type broad response were located at regions outside of both the orthosteric ligand binding site and the allosteric binding site for inosine-5'-monophosphate (IMP), a known natural umami taste enhancer. Site-directed mutagenesis demonstrated that the newly identified key residues for the mouse-type responses modulated receptor activity in a manner distinct from that of the allosteric modulation via IMP. Analyses of multiple point mutants suggested that the combination of two distinct determinants, amino acid selectivity at the orthosteric site and receptor activity modulation at the non-orthosteric sites, may mediate the ligand specificity of T1R1/T1R3. This hypothesis was supported by the results of studies using nonhuman primate T1R1 receptors. A complex molecular mechanism involving changes in the properties of both the orthosteric and non-orthosteric sites of T1R1 underlies the determination of ligand specificity in mammalian T1R1/T1R3. PMID- 24214977 TI - Functional identification of the hypoxanthine/guanine transporters YjcD and YgfQ and the adenine transporters PurP and YicO of Escherichia coli K-12. AB - The evolutionarily broad family nucleobase-cation symporter-2 (NCS2) encompasses transporters that are conserved in binding site architecture but diverse in substrate selectivity. Putative purine transporters of this family fall into one of two homology clusters: COG2233, represented by well studied xanthine and/or uric acid permeases, and COG2252, consisting of transporters for adenine, guanine, and/or hypoxanthine that remain unknown with respect to structure function relationships. We analyzed the COG2252 genes of Escherichia coli K-12 with homology modeling, functional overexpression, and mutagenesis and showed that they encode high affinity permeases for the uptake of adenine (PurP and YicO) or guanine and hypoxanthine (YjcD and YgfQ). The two pairs of paralogs differ clearly in their substrate and ligand preferences. Of 25 putative inhibitors tested, PurP and YicO recognize with low micromolar affinity N(6) benzoyladenine, 2,6-diaminopurine, and purine, whereas YjcD and YgfQ recognize 1 methylguanine, 8-azaguanine, 6-thioguanine, and 6-mercaptopurine and do not recognize any of the PurP ligands. Furthermore, the permeases PurP and YjcD were subjected to site-directed mutagenesis at highly conserved sites of transmembrane segments 1, 3, 8, 9, and 10, which have been studied also in COG2233 homologs. Residues irreplaceable for uptake activity or crucial for substrate selectivity were found at positions occupied by similar role amino acids in the Escherichia coli xanthine- and uric acid-transporting homologs (XanQ and UacT, respectively) and predicted to be at or around the binding site. Our results support the contention that the distantly related transporters of COG2233 and COG2252 use topologically similar side chain determinants to dictate their function and the distinct purine selectivity profiles. PMID- 24214978 TI - O-GlcNAcylation of cofilin promotes breast cancer cell invasion. AB - O-GlcNAcylation is a post-translational modification that regulates a broad range of nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes. Previous studies have shown that increased levels of global O-GlcNAcylation and O-GlcNAc transferase (OGT) are linked to the incidence of metastasis in breast cancer patients, but the molecular basis behind this is not fully known. In this study, we have determined that the actin-binding protein cofilin is O-GlcNAcylated by OGT and mainly, if not completely, mediates OGT modulation of cell mobility. O-GlcNAcylation at Ser-108 of cofilin is required for its proper localization in invadopodia at the leading edge of breast cancer cells during three-dimensional cell invasion. Loss of O-GlcNAcylation of cofilin leads to destabilization of invadopodia and impairs cell invasion, although the actin-severing activity or lamellipodial localization is not affected. Our study provides insights into the mechanism of post-translational modification in fine tuning the regulation of cofilin activity and suggests its important implications in cancer metastasis. PMID- 24214979 TI - Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor. AB - To survive and replicate within the human host, malaria parasites must invade erythrocytes. Invasion can be mediated by the P. falciparum reticulocyte-binding homologue protein 4 (PfRh4) on the merozoite surface interacting with complement receptor type 1 (CR1, CD35) on the erythrocyte membrane. The PfRh4 attachment site lies within the three N-terminal complement control protein modules (CCPs 1 3) of CR1, which intriguingly also accommodate binding and regulatory sites for the key complement activation-specific proteolytic products, C3b and C4b. One of these regulatory activities is decay-accelerating activity. Although PfRh4 does not impact C3b/C4b binding, it does inhibit this convertase disassociating capability. Here, we have employed ELISA, co-immunoprecipitation, and surface plasmon resonance to demonstrate that CCP 1 contains all the critical residues for PfRh4 interaction. We fine mapped by homologous substitution mutagenesis the PfRh4-binding site on CCP 1 and visualized it with a solution structure of CCPs 1 3 derived by NMR and small angle x-ray scattering. We cross-validated these results by creating an artificial PfRh4-binding site through substitution of putative PfRh4-interacting residues from CCP 1 into their homologous positions within CCP 8; strikingly, this engineered binding site had an ~30-fold higher affinity for PfRh4 than the native one in CCP 1. These experiments define a candidate site on CR1 by which P. falciparum merozoites gain access to human erythrocytes in a non-sialic acid-dependent pathway of merozoite invasion. PMID- 24214980 TI - Histone deacetylase sirtuin 1 deacetylates IRF1 protein and programs dendritic cells to control Th17 protein differentiation during autoimmune inflammation. AB - The type III histone deacetylase Sirt1 has recently emerged as a critical immune regulator by suppressing T cell immunity and macrophage activation during inflammation, but its role in dendritic cells (DCs) remains unknown. Here, we show that mice with genetic Sirt1 deletion specifically in DCs are resistant to MOG-induced experimental autoimmune encephalomyelitis. Loss of Sirt1 functions in DCs enhances their ability to produce IL-27 and interferon beta (IFN-beta). Co cultivation of Sirt1-null DCs with CD4(+) T cells inhibited Th17 differentiation, which is reversed by anti-IL27 and anti-IFN-beta neutralization antibodies. Sirt1 antagonizes acetylation of IRF1, a transcription factor that drives IL-27 production. Genetic deletion of IRF1 in Sirt1-null DCs abolishes IL-27 production and suppresses Th17 differentiation. Our results show that the histone deacetylase Sirt1 programs DCs to regulate Th17 differentiation during inflammation. PMID- 24214981 TI - A phosphoinositide 3-kinase (PI3K)-serum- and glucocorticoid-inducible kinase 1 (SGK1) pathway promotes Kv7.1 channel surface expression by inhibiting Nedd4-2 protein. AB - Epithelial cell polarization involves several kinase signaling cascades that eventually divide the surface membrane into an apical and a basolateral part. One kinase, which is activated during the polarization process, is phosphoinositide 3 kinase (PI3K). In MDCK cells, the basolateral potassium channel Kv7.1 requires PI3K activity for surface-expression during the polarization process. Here, we demonstrate that Kv7.1 surface expression requires tonic PI3K activity as PI3K inhibition triggers endocytosis of these channels in polarized MDCK. Pharmacological inhibition of SGK1 gave similar results as PI3K inhibition, whereas overexpression of constitutively active SGK1 overruled it, suggesting that SGK1 is the primary downstream target of PI3K in this process. Furthermore, knockdown of the ubiquitin ligase Nedd4-2 overruled PI3K inhibition, whereas a Nedd4-2 interaction-deficient Kv7.1 mutant was resistant to both PI3K and SGK1 inhibition. Altogether, these data suggest that a PI3K-SGK1 pathway stabilizes Kv7.1 surface expression by inhibiting Nedd4-2-dependent endocytosis and thereby demonstrates that Nedd4-2 is a key regulator of Kv7.1 localization and turnover in epithelial cells. PMID- 24214982 TI - Evidence that GH115 alpha-glucuronidase activity, which is required to degrade plant biomass, is dependent on conformational flexibility. AB - The microbial degradation of the plant cell wall is an important biological process that is highly relevant to environmentally significant industries such as the bioenergy and biorefining sectors. A major component of the wall is glucuronoxylan, a beta1,4-linked xylose polysaccharide that is decorated with alpha-linked glucuronic and/or methylglucuronic acid (GlcA/MeGlcA). Recently three members of a glycoside hydrolase family, GH115, were shown to hydrolyze MeGlcA side chains from the internal regions of xylan, an activity that has not previously been described. Here we show that a dominant member of the human microbiota, Bacteroides ovatus, contains a GH115 enzyme, BoAgu115A, which displays glucuronoxylan alpha-(4-O-methyl)-glucuronidase activity. The enzyme is significantly more active against substrates in which the xylose decorated with GlcA/MeGlcA is flanked by one or more xylose residues. The crystal structure of BoAgu115A revealed a four-domain protein in which the active site, comprising a pocket that abuts a cleft-like structure, is housed in the second domain that adopts a TIM barrel-fold. The third domain, a five-helical bundle, and the C terminal beta-sandwich domain make inter-chain contacts leading to protein dimerization. Informed by the structure of the enzyme in complex with GlcA in its open ring form, in conjunction with mutagenesis studies, the potential substrate binding and catalytically significant amino acids were identified. Based on the catalytic importance of residues located on a highly flexible loop, the enzyme is required to undergo a substantial conformational change to form a productive Michaelis complex with glucuronoxylan. PMID- 24214983 TI - A novel family of human leukocyte antigen class II receptors may have its origin in archaic human species. AB - HLA class II alpha and beta chains form receptors for antigen presentation to CD4(+) T cells. Numerous pairings of class II alpha and beta subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched alphabeta heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study we investigated assembly of isotype-mixed HLA class II alpha and beta heterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed alpha and beta subunits was dependent on the groove binding section of the invariant chain (Ii). By mutation of polymorphic DPbeta sequences, we identified two motifs, Lys-69 and GGPM-(84-87), that are engaged in Ii-dependent assembly of DPbeta with DRalpha. We identified five members of a family of DPbeta chains containing Lys-69 and GGPM 84-87, which assemble with DRalpha. The Lys/GGPM motif is present in the DPbeta sequence of the Neanderthal genome, and this ancient sequence is related to the human allele DPB1*0401. By site-directed mutagenesis, we inspected Neanderthal amino acid residues that differ from the DPB1*0401 allele and aimed to determine whether matched heterodimers are formed by assembly of DPbeta mutants with DRalpha. Because the *0401 allele is rare in the sub-Saharan population but frequent in the European population, it may have arisen in modern humans by admixture with Neanderthals in Europe. PMID- 24214984 TI - Complex N-glycosylation stabilizes surface expression of transient receptor potential melastatin 4b protein. AB - N-glycosylation is important for the function and regulation of ion channels. We examined the role of N-glycosylation of transient receptor potential melastatin (Trpm) 4b, a membrane glycoprotein that regulates calcium influx. Trpm4b was expressed in vivo in all rat tissues examined. In each tissue, Trpm4b had a different molecular mass, between ~129 and ~141 kDa, but all reverted to ~120 kDa following treatment with peptide:N-glycosidase F, consistent with N-glycosylation being the principal form of post-translational modification of Trpm4b in vivo. In six stable isogenic cell lines that express different levels of Trpm4b, two forms were found, high mannose, core-glycosylated and complex, highly glycosylated (HG), with HG-Trpm4b comprising 85% of the total Trpm4b expressed. For both forms, surface expression was directly proportional to the total Trpm4b expressed. Complex N-glycosylation doubled the percentage of Trpm4b at the surface, compared with high mannose N-glycosylation. Mutation of the single N glycosylation consensus sequence at Asn-988 (Trpm4b-N988Q), located near the pore forming loop between transmembrane helices 5 and 6, prevented glycosylation, but did not prevent surface expression, impair formation of functional membrane channels, or alter channel conductance. In transfection experiments, the time courses for appearance of HG-Trpm4b and Trpm4b-N988Q on the surface were similar. In experiments with cycloheximide inhibition of protein synthesis, the time course for disappearance of HG-Trpm4b from the surface was much slower than that for Trpm4b-N988Q. We conclude that N-glycosylation is not required for surface expression or channel function, but that complex N-glycosylation plays a crucial role in stabilizing surface expression of Trpm4b. PMID- 24214985 TI - Control of histone H3 lysine 9 (H3K9) methylation state via cooperative two-step demethylation by Jumonji domain containing 1A (JMJD1A) homodimer. AB - Post-translational histone methylation is a dynamic and reversible process that is involved in the spatio-temporal regulation of gene transcription and contributes to various cellular phenotypes. Methylation of histone H3 at lysine 9 (H3K9), which is generally a transcriptional repression mark, is demethylated by H3K9-specific demethylases, leading to transcriptional activation. However, how multiple demethylases with the same substrate specificity differ in their chromatin targeting mechanisms has not been well understood. Unlike other H3K9 specific demethylases, it has been reported that JMJD1A likely forms a homodimer, but a detailed mode of dimerization and the possible link between structure and enzymatic activity have remained unresolved. Here, we report the structure function relationship of JMJD1A in detail. First, JMJD1A forms a homodimer through its catalytic domains, bringing the two active sites close together. Second, increasing the concentration of JMJD1A facilitates efficient production of unmethylated product from dimethyl-H3K9 and decreases the release of the monomethylated intermediate. Finally, substituting one of the two active sites with an inactive mutant results in a significant reduction of the demethylation rate without changing the affinity to the intermediate. Given this evidence, we propose a substrate channeling model for the efficient conversion of dimethylated H3K9 into the unmethylated state. Our study provides valuable information that will help in understanding the redundancy of H3K9-specific demethylases and the complementary activity of their unique structures and enzymatic properties for appropriate control of chromatin modification patterns. PMID- 24214986 TI - Myosin 3A kinase activity is regulated by phosphorylation of the kinase domain activation loop. AB - Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr 184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self regulate its concentration in the actin bundle-based structures of cells. PMID- 24214987 TI - UniHI 7: an enhanced database for retrieval and interactive analysis of human molecular interaction networks. AB - Unified Human Interactome (UniHI) (http://www.unihi.org) is a database for retrieval, analysis and visualization of human molecular interaction networks. Its primary aim is to provide a comprehensive and easy-to-use platform for network-based investigations to a wide community of researchers in biology and medicine. Here, we describe a major update (version 7) of the database previously featured in NAR Database Issue. UniHI 7 currently includes almost 350,000 molecular interactions between genes, proteins and drugs, as well as numerous other types of data such as gene expression and functional annotation. Multiple options for interactive filtering and highlighting of proteins can be employed to obtain more reliable and specific network structures. Expression and other genomic data can be uploaded by the user to examine local network structures. Additional built-in tools enable ready identification of known drug targets, as well as of biological processes, phenotypes and pathways enriched with network proteins. A distinctive feature of UniHI 7 is its user-friendly interface designed to be utilized in an intuitive manner, enabling researchers less acquainted with network analysis to perform state-of-the-art network-based investigations. PMID- 24214988 TI - SAbDab: the structural antibody database. AB - Structural antibody database (SAbDab; http://opig.stats.ox.ac.uk/webapps/sabdab) is an online resource containing all the publicly available antibody structures annotated and presented in a consistent fashion. The data are annotated with several properties including experimental information, gene details, correct heavy and light chain pairings, antigen details and, where available, antibody antigen binding affinity. The user can select structures, according to these attributes as well as structural properties such as complementarity determining region loop conformation and variable domain orientation. Individual structures, datasets and the complete database can be downloaded. PMID- 24214989 TI - Assembly information services in the European Nucleotide Archive. AB - The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is a repository for the world public domain nucleotide sequence data output. ENA content covers a spectrum of data types including raw reads, assembly data and functional annotation. ENA has faced a dramatic growth in genome assembly submission rates, data volumes and complexity of datasets. This has prompted a broad reworking of assembly submission services, for which we now reach the end of a major programme of work and many enhancements have already been made available over the year to components of the submission service. In this article, we briefly review ENA content and growth over 2013, describe our rapidly developing services for genome assembly information and outline further major developments over the last year. PMID- 24214990 TI - Eukaryotic rpL10 drives ribosomal rotation. AB - Ribosomes transit between two conformational states, non-rotated and rotated, through the elongation cycle. Here, we present evidence that an internal loop in the essential yeast ribosomal protein rpL10 is a central controller of this process. Mutations in this loop promote opposing effects on the natural equilibrium between these two extreme conformational states. rRNA chemical modification analyses reveals allosteric interactions involved in coordinating intersubunit rotation originating from rpL10 in the core of the large subunit (LSU) through both subunits, linking all the functional centers of the ribosome. Mutations promoting rotational disequilibria showed catalytic, biochemical and translational fidelity defects. An rpL3 mutation promoting opposing structural and biochemical effects, suppressed an rpL10 mutant, re-establishing rotational equilibrium. The rpL10 loop is also involved in Sdo1p recruitment, suggesting that rotational status is important for ensuring late-stage maturation of the LSU, supporting a model in which pre-60S subunits undergo a 'test drive' before final maturation. PMID- 24214991 TI - EKPD: a hierarchical database of eukaryotic protein kinases and protein phosphatases. AB - We present here EKPD (http://ekpd.biocuckoo.org), a hierarchical database of eukaryotic protein kinases (PKs) and protein phosphatases (PPs), the key molecules responsible for the reversible phosphorylation of proteins that are involved in almost all aspects of biological processes. As extensive experimental and computational efforts have been carried out to identify PKs and PPs, an integrative resource with detailed classification and annotation information would be of great value for both experimentalists and computational biologists. In this work, we first collected 1855 PKs and 347 PPs from the scientific literature and various public databases. Based on previously established rationales, we classified all of the known PKs and PPs into a hierarchical structure with three levels, i.e. group, family and individual PK/PP. There are 10 groups with 149 families for the PKs and 10 groups with 33 families for the PPs. We constructed 139 and 27 Hidden Markov Model profiles for PK and PP families, respectively. Then we systematically characterized ~50,000 PKs and >10,000 PPs in eukaryotes. In addition, >500 PKs and >400 PPs were computationally identified by ortholog search. Finally, the online service of the EKPD database was implemented in PHP + MySQL + JavaScript. PMID- 24214992 TI - Redox-active quinones induces genome-wide DNA methylation changes by an iron mediated and Tet-dependent mechanism. AB - DNA methylation has been proven to be a critical epigenetic mark important for various cellular processes. Here, we report that redox-active quinones, a ubiquitous class of chemicals found in natural products, cancer therapeutics and environment, stimulate the conversion of 5 mC to 5 hmC in vivo, and increase 5 hmC in 5751 genes in cells. 5 hmC increase is associated with significantly altered gene expression of 3414 genes. Interestingly, in quinone-treated cells, labile iron-sensitive protein ferritin light chain showed a significant increase at both mRNA and protein levels indicating a role of iron regulation in stimulating Tet-mediated 5 mC oxidation. Consistently, the deprivation of cellular labile iron using specific chelator blocked the 5 hmC increase, and a delivery of labile iron increased the 5 hmC level. Moreover, both Tet1/Tet2 knockout and dimethyloxalylglycine-induced Tet inhibition diminished the 5 hmC increase. These results suggest an iron-regulated Tet-dependent DNA demethylation mechanism mediated by redox-active biomolecules. PMID- 24214993 TI - CPLM: a database of protein lysine modifications. AB - We reported an integrated database of Compendium of Protein Lysine Modifications (CPLM; http://cplm.biocuckoo.org) for protein lysine modifications (PLMs), which occur at active epsilon-amino groups of specific lysine residues in proteins and are critical for orchestrating various biological processes. The CPLM database was updated from our previously developed database of Compendium of Protein Lysine Acetylation (CPLA), which contained 7151 lysine acetylation sites in 3311 proteins. Here, we manually collected experimentally identified substrates and sites for 12 types of PLMs, including acetylation, ubiquitination, sumoylation, methylation, butyrylation, crotonylation, glycation, malonylation, phosphoglycerylation, propionylation, succinylation and pupylation. In total, the CPLM database contained 203,972 modification events on 189,919 modified lysines in 45,748 proteins for 122 species. With the dataset, we totally identified 76 types of co-occurrences of various PLMs on the same lysine residues, and the most abundant PLM crosstalk is between acetylation and ubiquitination. Up to 53.5% of acetylation and 33.1% of ubiquitination events co-occur at 10 746 lysine sites. Thus, the various PLM crosstalks suggested that a considerable proportion of lysines were competitively and dynamically regulated in a complicated manner. Taken together, the CPLM database can serve as a useful resource for further research of PLMs. PMID- 24214994 TI - Timing of GTP binding and hydrolysis by translation termination factor RF3. AB - Protein synthesis in bacteria is terminated by release factors 1 or 2 (RF1/2), which, on recognition of a stop codon in the decoding site on the ribosome, promote the hydrolytic release of the polypeptide from the transfer RNA (tRNA). Subsequently, the dissociation of RF1/2 is accelerated by RF3, a guanosine triphosphatase (GTPase) that hydrolyzes GTP during the process. Here we show that -in contrast to a previous report--RF3 binds GTP and guanosine diphosphate (GDP) with comparable affinities. Furthermore, we find that RF3-GTP binds to the ribosome and hydrolyzes GTP independent of whether the P site contains peptidyl tRNA (pre-termination state) or deacylated tRNA (post-termination state). RF3-GDP in either pre- or post-termination complexes readily exchanges GDP for GTP, and the exchange is accelerated when RF2 is present on the ribosome. Peptide release results in the stabilization of the RF3-GTP-ribosome complex, presumably due to the formation of the hybrid/rotated state of the ribosome, thereby promoting the dissociation of RF1/2. GTP hydrolysis by RF3 is virtually independent of the functional state of the ribosome and the presence of RF2, suggesting that RF3 acts as an unregulated ribosome-activated switch governed by its internal GTPase clock. PMID- 24214995 TI - TPM analyses reveal that FtsK contributes both to the assembly and the activation of the XerCD-dif recombination synapse. AB - Circular chromosomes can form dimers during replication and failure to resolve those into monomers prevents chromosome segregation, which leads to cell death. Dimer resolution is catalysed by a highly conserved site-specific recombination system, called XerCD-dif in Escherichia coli. Recombination is activated by the DNA translocase FtsK, which is associated with the division septum, and is thought to contribute to the assembly of the XerCD-dif synapse. In our study, direct observation of the assembly of the XerCD-dif synapse, which had previously eluded other methods, was made possible by the use of Tethered Particle Motion, a single molecule approach. We show that XerC, XerD and two dif sites suffice for the assembly of XerCD-dif synapses in absence of FtsK, but lead to inactive XerCD dif synapses. We also show that the presence of the gamma domain of FtsK increases the rate of synapse formation and convert them into active synapses where recombination occurs. Our results represent the first direct observation of the formation of the XerCD-dif recombination synapse and its activation by FtsK. PMID- 24214996 TI - Negatome 2.0: a database of non-interacting proteins derived by literature mining, manual annotation and protein structure analysis. AB - Knowledge about non-interacting proteins (NIPs) is important for training the algorithms to predict protein-protein interactions (PPIs) and for assessing the false positive rates of PPI detection efforts. We present the second version of Negatome, a database of proteins and protein domains that are unlikely to engage in physical interactions (available online at http://mips.helmholtz muenchen.de/proj/ppi/negatome). Negatome is derived by manual curation of literature and by analyzing three-dimensional structures of protein complexes. The main methodological innovation in Negatome 2.0 is the utilization of an advanced text mining procedure to guide the manual annotation process. Potential non-interactions were identified by a modified version of Excerbt, a text mining tool based on semantic sentence analysis. Manual verification shows that nearly a half of the text mining results with the highest confidence values correspond to NIP pairs. Compared to the first version the contents of the database have grown by over 300%. PMID- 24214997 TI - Alternative splicing of a group II intron in a surface layer protein gene in Clostridium tetani. AB - Group II introns are ribozymes and retroelements found in bacteria, and are thought to have been the ancestors of nuclear pre-mRNA introns. Whereas nuclear introns undergo prolific alternative splicing in some species, group II introns are not known to carry out equivalent reactions. Here we report a group II intron in the human pathogen Clostridium tetani, which undergoes four alternative splicing reactions in vivo. Together with unspliced transcript, five mRNAs are produced, each encoding a distinct surface layer protein isoform. Correct fusion of exon reading frames requires a shifted 5' splice site located 8 nt upstream of the canonical boundary motif. The shifted junction is accomplished by an altered IBS1-EBS1 pairing between the intron and 5' exon. Growth of C. tetani under a variety of conditions did not result in large changes in alternative splicing levels, raising the possibility that alternative splicing is constitutive. This work demonstrates a novel type of gene organization and regulation in bacteria, and provides an additional parallel between group II and nuclear pre-mRNA introns. PMID- 24214998 TI - COLOMBOS v2.0: an ever expanding collection of bacterial expression compendia. AB - The COLOMBOS database (http://www.colombos.net) features comprehensive organism specific cross-platform gene expression compendia of several bacterial model organisms and is supported by a fully interactive web portal and an extensive web API. COLOMBOS was originally published in PLoS One, and COLOMBOS v2.0 includes both an update of the expression data, by expanding the previously available compendia and by adding compendia for several new species, and an update of the surrounding functionality, with improved search and visualization options and novel tools for programmatic access to the database. The scope of the database has also been extended to incorporate RNA-seq data in our compendia by a dedicated analysis pipeline. We demonstrate the validity and robustness of this approach by comparing the same RNA samples measured in parallel using both microarrays and RNA-seq. As far as we know, COLOMBOS currently hosts the largest homogenized gene expression compendia available for seven bacterial model organisms. PMID- 24214999 TI - Just desserts from our poor food safety culture? PMID- 24215002 TI - Importance of handwashing in food handling. PMID- 24215003 TI - Offshore installations benefit from nutrition training programmes. PMID- 24215005 TI - RSPH Annual Conference and Awards Ceremony: diversity and change - better health in the United Kingdom. PMID- 24215004 TI - Food security in America. PMID- 24215006 TI - Transforming food culture in schools, communities and throughout the life course. PMID- 24215007 TI - Using silver to help combat Campylobacter and other bacteria. PMID- 24215008 TI - The risk assessment: an intrinsic part of environmental health, public health - and life. PMID- 24215009 TI - Mixed messages in food safety: killing us softly? PMID- 24215010 TI - HEY! A practical example of promoting healthy lifestyles in the early years. PMID- 24215011 TI - The hygiene hypothesis: identifying microbial friends and protecting against microbial enemies. PMID- 24215012 TI - Developing food safety cultures - are small catering businesses being neglected? PMID- 24215013 TI - Reactions, regulation and risk: protecting consumers with food allergies and intolerances. PMID- 24215014 TI - Can a school-based intervention increase children's fruit and vegetable consumption in the home setting? AB - AIMS: Although previous research has shown the Food Dudes programme increases children's fruit and vegetable consumption at school, the evidence for the effectiveness in the home setting is more equivocal. The school environment is identified as a logical setting for targeting children's fruit and vegetable consumption; however, to produce sustainable changes in behaviour, it is equally important that interventions target consumption in the home setting. This study aimed to establish whether the Food Dudes intervention can influence home consumption of fruit and vegetables and the extent to which any changes in eating behaviour following the intervention were maintained in the long term. METHODS: A total of 34 children aged 4-11 years from eight primary schools (four intervention and four control groups) in the West Midlands, United Kingdom, completed a 7-day photographic food diary at baseline (prior to the intervention), a 3-month follow-up (post-intervention) and a 12-month follow-up. RESULTS: The Food Dudes programme did not influence either short- or long-term changes in children's consumption of fruit and vegetables at home during weekdays or at the weekend. CONCLUSIONS: The Food Dudes programme had no effect on changing children's fruit and vegetable consumption in the home environment. Further development of the programme could consider how parental and home environmental factors may be combined with the principles of the Food Dudes programme to influence children's fruit and vegetable consumption in this setting. PMID- 24215016 TI - Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease. AB - BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of alpha-galactosidase A (alpha-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading to end stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant alpha-Gal A reduces cellular GL-3 deposits in podocytes and tubular epithelial cells. We have previously shown that alpha-Gal A is delivered to these cells by different pathways involving different receptors. This study investigated the long-term changes in albuminuria, estimated glomerular filtration rate (eGFR) and urinary markers of both glomerular and tubular dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile, including the glomerular marker IgG, the tubular markers alpha1-microglobulin and retinol-binding protein (RBP), and the shared tubular and glomerular markers albumin and transferrin. RESULTS: ERT was associated with a significant reduction in albuminuria and a relatively stable eGFR. The decrease in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. CONCLUSIONS: The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations. PMID- 24215017 TI - Time-averaged level of fibroblast growth factor-23 and clinical events in chronic kidney disease. AB - BACKGROUND: A single time-point fibroblast growth factor-23 (FGF23) level is a strong, well-established risk factor for clinical events in chronic kidney disease (CKD). This study investigated whether repeated measurements of FGF23 after 2 years, allowing the calculation of time-averaged FGF23 and the rate of change in FGF23, provided a better prediction of clinical events in CKD than a single time-point value. METHODS: A post-hoc analysis was performed in a subset of 439 adult patients with a median estimated glomerular filtration rate of 36 (interquartile range 28-48) mL/min per 1.73 m(2) of the prospective multicentre MASTERPLAN study, in which paired samples to measure FGF23 were available. The primary outcome was defined as a composite of myocardial infarction, stroke and cardiovascular mortality and secondary end points, which were overall mortality, congestive heart failure (CHF) and start of renal replacement therapy. Only events occurring after Month 24 were included in the analysis. RESULTS: Analysis of different FGF23 measures showed that a single time-point value and time averaged FGF23 were positively associated with the primary end point, and also with overall mortality, start of renal replacement therapy and CHF. The adjusted hazard ratios of a single value of FGF23 and of time-averaged FGF23 for the composite end points were 1.71 (CI 1.20-2.43) and 1.91 (CI 1.29-2.82), respectively. Change in FGF23 was not associated with any outcome except for the initiation of renal replacement therapy. CONCLUSIONS: Our study confirms that FGF23 is an important cardiovascular risk factor. Two measurements of FGF23 have no added value over a single value to predict the cardiovascular outcome. This study demonstrates that, under routine clinical practice, the variability of FGF23 in 2 years' time is small. Concomitantly, this study showed no benefit of consecutive FGF23 testing for estimating the risk of a clinical event in an individual patient. PMID- 24215018 TI - Extra-renal manifestations of autosomal dominant polycystic kidney disease (ADPKD): considerations for routine screening and management. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is a systemic disease, marked by progressive increase of bilateral renal cysts, resulting in chronic kidney disease (CKD) and often leading to end-stage renal disease (ESRD). Apart from renal cysts, patients often have extra-renal disease, involving the liver, heart and vasculature. Other less common but equally important extra-renal manifestations of ADPKD include diverticular disease, hernias, male infertility and pain. Extra-renal disease burden is often asymptomatic, but may result in increased morbidity and mortality. If the disease burden is significant, screening may prove beneficial. We review the rationale for current screening recommendations and propose some guidelines for screening and management of ADPKD patients. PMID- 24215020 TI - Development of a domain-specific genetic language to design Chlamydomonas reinhardtii expression vectors. AB - MOTIVATION: Expression vectors used in different biotechnology applications are designed with domain-specific rules. For instance, promoters, origins of replication or homologous recombination sites are host-specific. Similarly, chromosomal integration or viral delivery of an expression cassette imposes specific structural constraints. As de novo gene synthesis and synthetic biology methods permeate many biotechnology specialties, the design of application specific expression vectors becomes the new norm. In this context, it is desirable to formalize vector design strategies applicable in different domains. RESULTS: Using the design of constructs to express genes in the chloroplast of Chlamydomonas reinhardtii as an example, we show that a vector design strategy can be formalized as a domain-specific language. We have developed a graphical editor of context-free grammars usable by biologists without prior exposure to language theory. This environment makes it possible for biologists to iteratively improve their design strategies throughout the course of a project. It is also possible to ensure that vectors designed with early iterations of the language are consistent with the latest iteration of the language. AVAILABILITY AND IMPLEMENTATION: The context-free grammar editor is part of the GenoCAD application. A public instance of GenoCAD is available at http://www.genocad.org. GenoCAD source code is available from SourceForge and licensed under the Apache v2.0 open source license. PMID- 24215021 TI - A MATLAB-based tool for accurate detection of perfect overlapping and nested inverted repeats in DNA sequences. AB - SUMMARY: Palindromic sequences, or inverted repeats (IRs), in DNA sequences involve important biological processes such as DNA-protein binding, DNA replication and DNA transposition. Development of bioinformatics tools that are capable of accurately detecting perfect IRs can enable genome-wide studies of IR patterns in both prokaryotes and eukaryotes. Different from conventional string comparison approaches, we propose a novel algorithm that uses a cumulative score system based on a prime number representation of nucleotide bases. We then implemented this algorithm as a MATLAB-based program for perfect IR detection. In comparison with other existing tools, our program demonstrates a high accuracy in detecting nested and overlapping IRs. AVAILABILITY AND IMPLEMENTATION: The source code is freely available on (http://bioinfolab.miamioh.edu/bioinfolab/palindrome.php) CONTACT: liangc@miamioh.edu or karroje@miamioh.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24215022 TI - Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing. AB - MOTIVATION: Long expansions of short tandem repeats (STRs), i.e. DNA repeats of 2 6 nt, are associated with some genetic diseases. Cost-efficient high-throughput sequencing can quickly produce billions of short reads that would be useful for uncovering disease-associated STRs. However, enumerating STRs in short reads remains largely unexplored because of the difficulty in elucidating STRs much longer than 100 bp, the typical length of short reads. RESULTS: We propose ab initio procedures for sensing and locating long STRs promptly by using the frequency distribution of all STRs and paired-end read information. We validated the reproducibility of this method using biological replicates and used it to locate an STR associated with a brain disease (SCA31). Subsequently, we sequenced this STR site in 11 SCA31 samples using SMRT(TM) sequencing (Pacific Biosciences), determined 2.3-3.1 kb sequences at nucleotide resolution and revealed that (TGGAA)- and (TAAAATAGAA)-repeat expansions determined the instability of the repeat expansions associated with SCA31. Our method could also identify common STRs, (AAAG)- and (AAAAG)-repeat expansions, which are remarkably expanded at four positions in an SCA31 sample. This is the first proposed method for rapidly finding disease-associated long STRs in personal genomes using hybrid sequencing of short and long reads. AVAILABILITY AND IMPLEMENTATION: Our TRhist software is available at http://trhist.gi.k.u-tokyo.ac.jp/. CONTACT: moris@cb.k.u tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24215023 TI - RNAseqViewer: visualization tool for RNA-Seq data. AB - SUMMARY: With the advances of RNA sequencing technologies, scientists need new tools to analyze transcriptome data. We introduce RNAseqViewer, a new visualization tool dedicated to RNA-Seq data. The program offers innovative ways to represent transcriptome data for single or multiple samples. It is a handy tool for scientists who use RNA-Seq data to compare multiple transcriptomes, for example, to compare gene expression and alternative splicing of cancer samples or of different development stages. AVAILABILITY AND IMPLEMENTATION: RNAseqViewer is freely available for academic use at http://bioinfo.au.tsinghua.edu.cn/software/RNAseqViewer/ CONTACT: zhangxg@tsinghua.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24215024 TI - SBML and CellML translation in antimony and JSim. AB - MOTIVATION: The creation and exchange of biologically relevant models is of great interest to many researchers. When multiple standards are in use, models are more readily used and re-used if there exist robust translators between the various accepted formats. SUMMARY: Antimony 2.4 and JSim 2.10 provide translation capabilities from their own formats to SBML and CellML. All provided unique challenges, stemming from differences in each format's inherent design, in addition to differences in functionality. AVAILABILITY AND IMPLEMENTATION: Both programs are available under BSD licenses; Antimony from http://antimony.sourceforge.net/and JSim from http://physiome.org/jsim/. CONTACT: lpsmith@u.washington.edu. PMID- 24215025 TI - RelateAdmix: a software tool for estimating relatedness between admixed individuals. AB - MOTIVATION: Pairwise relatedness plays an important role in a range of genetic research fields. However, currently only few estimators exist for individuals that are admixed, i.e. have ancestry from more than one population, and these estimators fail in some situations. RESULTS: We present a new software tool, RelateAdmix, for obtaining maximum likelihood estimates of pairwise relatedness from genetic data between admixed individuals. We show using simulated data that it gives rise to better estimates than three state-of-the-art software tools, REAP, KING and Plink, while still being fast enough to be applicable to large datasets. AVAILABILITY AND IMPLEMENTATION: The software tool, implemented in C and R, is freely available from www.popgen.dk/software. PMID- 24215026 TI - PTMTreeSearch: a novel two-stage tree-search algorithm with pruning rules for the identification of post-translational modification of proteins in MS/MS spectra. AB - MOTIVATION: Tandem mass spectrometry has become a standard tool for identifying post-translational modifications (PTMs) of proteins. Algorithmic searches for PTMs from tandem mass spectrum data (MS/MS) tend to be hampered by noisy data as well as by a combinatorial explosion of search space. This leads to high uncertainty and long search-execution times. RESULTS: To address this issue, we present PTMTreeSearch, a new algorithm that uses a large database of known PTMs to identify PTMs from MS/MS data. For a given peptide sequence, PTMTreeSearch builds a computational tree wherein each path from the root to the leaves is labeled with the amino acids of a peptide sequence. Branches then represent PTMs. Various empirical tree pruning rules have been designed to decrease the search execution time by eliminating biologically unlikely solutions. PTMTreeSearch first identifies a relatively small set of high confidence PTM types, and in a second stage, performs a more exhaustive search on this restricted set using relaxed search parameter settings. An analysis of experimental data shows that using the same criteria for false discovery, PTMTreeSearch annotates more peptides than the current state-of-the-art methods and PTM identification algorithms, and achieves this at roughly the same execution time. PTMTreeSearch is implemented as a plugable scoring function in the X!Tandem search engine. AVAILABILITY: The source code of PTMTreeSearch and a demo server application can be found at http://net.icgeb.org/ptmtreesearch PMID- 24215027 TI - Bayesian network prior: network analysis of biological data using external knowledge. AB - MOTIVATION: Reverse engineering GI networks from experimental data is a challenging task due to the complex nature of the networks and the noise inherent in the data. One way to overcome these hurdles would be incorporating the vast amounts of external biological knowledge when building interaction networks. We propose a framework where GI networks are learned from experimental data using Bayesian networks (BNs) and the incorporation of external knowledge is also done via a BN that we call Bayesian Network Prior (BNP). BNP depicts the relation between various evidence types that contribute to the event 'gene interaction' and is used to calculate the probability of a candidate graph (G) in the structure learning process. RESULTS: Our simulation results on synthetic, simulated and real biological data show that the proposed approach can identify the underlying interaction network with high accuracy even when the prior information is distorted and outperforms existing methods. AVAILABILITY: Accompanying BNP software package is freely available for academic use at http://bioe.bilgi.edu.tr/BNP. CONTACT: hasan.otu@bilgi.edu.tr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24215028 TI - AVIA: an interactive web-server for annotation, visualization and impact analysis of genomic variations. AB - MOTIVATION: The plethora of information that emerges from large-scale genome characterization studies has triggered the development of computational frameworks and tools for efficient analysis, interpretation and visualization of genomic data. Functional annotation of genomic variations and the ability to visualize the data in the context of whole genome and/or multiple genomes has remained a challenging task. We have developed an interactive web-based tool, AVIA (Annotation, Visualization and Impact Analysis), to explore and interpret large sets of genomic variations (single nucleotide variations and insertion/deletions) and to help guide and summarize genomic experiments. The annotation, summary plots and tables are packaged and can be downloaded by the user from the email link provided. AVAILABILITY AND IMPLEMENTATION: http://avia.abcc.ncifcrf.gov. PMID- 24215029 TI - HPC-CLUST: distributed hierarchical clustering for large sets of nucleotide sequences. AB - MOTIVATION: Nucleotide sequence data are being produced at an ever increasing rate. Clustering such sequences by similarity is often an essential first step in their analysis-intended to reduce redundancy, define gene families or suggest taxonomic units. Exact clustering algorithms, such as hierarchical clustering, scale relatively poorly in terms of run time and memory usage, yet they are desirable because heuristic shortcuts taken during clustering might have unintended consequences in later analysis steps. RESULTS: Here we present HPC CLUST, a highly optimized software pipeline that can cluster large numbers of pre aligned DNA sequences by running on distributed computing hardware. It allocates both memory and computing resources efficiently, and can process more than a million sequences in a few hours on a small cluster. AVAILABILITY AND IMPLEMENTATION: Source code and binaries are freely available at http://meringlab.org/software/hpc-clust/; the pipeline is implemented in Cpp and uses the Message Passing Interface (MPI) standard for distributed computing. PMID- 24215030 TI - Parallel content-based sub-image retrieval using hierarchical searching. AB - MOTIVATION: The capacity to systematically search through large image collections and ensembles and detect regions exhibiting similar morphological characteristics is central to pathology diagnosis. Unfortunately, the primary methods used to search digitized, whole-slide histopathology specimens are slow and prone to inter- and intra-observer variability. The central objective of this research was to design, develop, and evaluate a content-based image retrieval system to assist doctors for quick and reliable content-based comparative search of similar prostate image patches. METHOD: Given a representative image patch (sub-image), the algorithm will return a ranked ensemble of image patches throughout the entire whole-slide histology section which exhibits the most similar morphologic characteristics. This is accomplished by first performing hierarchical searching based on a newly developed hierarchical annular histogram (HAH). The set of candidates is then further refined in the second stage of processing by computing a color histogram from eight equally divided segments within each square annular bin defined in the original HAH. A demand-driven master-worker parallelization approach is employed to speed up the searching procedure. Using this strategy, the query patch is broadcasted to all worker processes. Each worker process is dynamically assigned an image by the master process to search for and return a ranked list of similar patches in the image. RESULTS: The algorithm was tested using digitized hematoxylin and eosin (H&E) stained prostate cancer specimens. We have achieved an excellent image retrieval performance. The recall rate within the first 40 rank retrieved image patches is ~90%. AVAILABILITY AND IMPLEMENTATION: Both the testing data and source code can be downloaded from http://pleiad.umdnj.edu/CBII/Bioinformatics/. PMID- 24215031 TI - A model-based correction for outcome reporting bias in meta-analysis. AB - It is often suspected (or known) that outcomes published in medical trials are selectively reported. A systematic review for a particular outcome of interest can only include studies where that outcome was reported and so may omit, for example, a study that has considered several outcome measures but only reports those giving significant results. Using the methodology of the Outcome Reporting Bias (ORB) in Trials study of (Kirkham and others, 2010. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. British Medical Journal 340, c365), we suggest a likelihood-based model for estimating the effect of ORB on confidence intervals and p-values in meta analysis. Correcting for bias has the effect of moving estimated treatment effects toward the null and hence more cautious assessments of significance. The bias can be very substantial, sometimes sufficient to completely overturn previous claims of significance. We re-analyze two contrasting examples, and derive a simple fixed effects approximation that can be used to give an initial estimate of the effect of ORB in practice. PMID- 24215032 TI - Two-year outcomes of intravitreal bevacizumab therapy for macular oedema secondary to branch retinal vein occlusion. AB - AIM: To determine the 2-year outcomes of intravitreal bevacizumab (IVB) injections in eyes with macular oedema (ME) following branch retinal vein occlusion (BRVO). METHODS: Of 105 consecutive eyes (105 treatment-naive patients) with ME following BRVO, 89 eyes were followed for 2 years after the first injection. During the 2-year follow-up period, patients were examined at least every 3 months and received an IVB injection (1.25 mg/0.05 mL) if they met prespecified retreatment criteria. Rescue grid laser was permitted based on the findings of the Branch Vein Occlusion Study. RESULTS: The baseline logarithm of the minimum angle of resolution visual acuity (VA) was 0.64+/-0.24 (mean+/-SD), which significantly (p=0.001) improved 1 month after the first injection to 0.39+/-0.22. One year after the first injection, VA improved significantly (p=0.001) to 0.33+/-0.21 and remained 0.34+/-0.21 until 2 years after the first injection (p=0.001). The changes in foveal thickness were correlated with those of VA during the 2-year follow-up period with a mean of 3.8+/-1.5 injections (including the first injection). CONCLUSIONS: This relatively large case series study showed favourable 2-year outcomes using bevacizumab to treat ME following BRVO. Bevacizumab provides substantial long-term benefits in the treatment of ME following BRVO. PMID- 24215034 TI - How I treat unexplained refractory iron deficiency anemia. AB - Endoscopic gastrointestinal workup fails to establish the cause of iron deficiency anemia (IDA) in a substantial proportion of patients. In patients referred for hematologic evaluation with unexplained or refractory IDA, screening for celiac disease, autoimmune gastritis, Helicobacter pylori, and hereditary forms of IDA is recommended. About 4% to 6% of patients with obscure refractory IDA have celiac disease, and autoimmune gastritis is encountered in 20% to 27% of patients. Stratification by age cohorts in autoimmune gastritis implies a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. Over 50% of patients with unexplained refractory IDA have active H pylori infection and, after excluding all other causes of IDA, 64% to 75% of such patients are permanently cured by H pylori eradication. In young patients with a history suggestive of hereditary iron deficiency with serum ferritin higher than expected for IDA, mutations involving iron trafficking and regulation should be considered. Recognition of the respective roles of H pylori, autoimmune gastritis, celiac disease, and genetic defects in the pathogenesis of iron deficiency should have a strong impact on the current diagnostic workup and management of unexplained, or refractory, IDA. PMID- 24215033 TI - Human proT-cells generated in vitro facilitate hematopoietic stem cell-derived T lymphopoiesis in vivo and restore thymic architecture. AB - Hematopoietic stem cell transplantation (HSCT) is followed by a period of immune deficiency due to a paucity in T-cell reconstitution. Underlying causes are a severely dysfunctional thymus and an impaired production of thymus-seeding progenitors in the host. Here, we addressed whether in vitro-derived human progenitor T (proT)-cells could not only represent a source of thymus-seeding progenitors, but also able to influence the recovery of the thymic microenvironment. We examined whether co-transplantation of in vitro-derived human proT-cells with hematopoietic stem cells (HSCs) was able to facilitate HSC derived T-lymphopoiesis posttransplant. A competitive transfer approach was used to define the optimal proT subset capable of reconstituting immunodeficient mice. Although the 2 subsets tested (proT1, CD34(+)CD7(+)CD5(-); proT2, CD34(+)CD7(+)CD5(+)) showed thymus engrafting function, proT2-cells exhibited superior engrafting capacity. Based on this, when proT2-cells were coinjected with HSCs, a significantly improved and accelerated HSC-derived T-lymphopoiesis was observed. Furthermore, we uncovered a potential mechanism by which receptor activator of nuclear factor kappab (RANK) ligand-expressing proT2-cells induce changes in both the function and architecture of the thymus microenvironment, which favors the recruitment of bone marrow-derived lymphoid progenitors. Our findings provide further support for the use of Notch-expanded progenitors in cell-based therapies to aid in the recovery of T-cells in patients undergoing HSCT. PMID- 24215035 TI - How I treat nodular lymphocyte predominant Hodgkin lymphoma. AB - Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon entity that, in contrast to classical Hodgkin lymphoma (cHL), universally expresses CD20, a hallmark of the disease. The majority of the patients present with early stage disease, and treatment with local radiation provides excellent disease control and overall survival (OS). For locally extensive or advanced stages, paradigms used for cHL have been employed, with similar outcomes. Unlike cHL, late relapses may occur, as well as a propensity to transform to an aggressive B cell non-Hodgkin lymphoma that underscores the importance of long-term follow-up and rebiopsy at the time of relapse. Deaths caused by NLPHL are uncommon, and in older series, secondary malignancies and other treatment-related toxicities contributed appreciably to overall mortality. Expression of CD20 in NLPHL has led to the evaluation of rituximab as a therapeutic option. Although results with single-agent rituximab in the front-line setting are inferior to conventional therapy, rituximab is a reasonable choice for relapsed disease because of the high overall response rate and excellent tolerability. Most patients have a long OS; therefore, overall goals of therapy should be to minimize the risk for relapse and long-term toxicity. PMID- 24215036 TI - The high cost to health and social care of managing falls in older adults living in the community in Scotland. AB - BACKGROUND AND AIMS: Estimate costs for health and social care services in managing older people in the community who fall. METHOD AND RESULTS: Analyses of predominantly national databases using cost of illness methodologies. In Scotland, 294,000 (34%) of people over 65 years and living in the community fall at least once a year. Of these 20%, almost 60,000 people contacted a medical service for assistance. There were almost 30,000 attendances at GP practices, over 36,100 calls to the Scottish Ambulance Service and 46,816 people presenting at A&E, with 16,549 admitted, 30% with a hip fracture. Mortality was high, 7% during the hospital stay, rising to over 12% at 1 year. Over 20% of patients were unable to return to their homes. Associated costs were over L470 million, with 60% incurred by social services, mainly providing long-term care. Cost per person falling was over L1720, rising to over L8600 for those seeking medical assistance. A hip fracture admission cost L39,490, compared with L21,960 for other falls-related admissions. CONCLUSIONS: Transparent, robust cost information demonstrates the substantial burden of falls for health and social care services and should be a driver for implementing evidence-based interventions to reduce falls. PMID- 24215037 TI - Learning safe practice by improving care: student-led intervention on oxygen prescribing in a respiratory ward. AB - BACKGROUND AND OBJECTIVE: The primary aim of this intervention was to improve oxygen prescribing in accordance with the 2008 British Thoracic Society guidelines for the prescription of emergency oxygen in adults. METHODS: Eight final year medical students reviewed the drug charts of all patients admitted to the respiratory ward on a daily basis in order to collect data on five audit questions: (1) Has oxygen (O2) been prescribed? (2) Has an O2 target saturation level been indicated? (3) Has O2 been prescribed as an 'as required' (PRN) or 'continuous therapy'? (4) Has the prescription been signed? (5) Has O2 been signed for in every drug round since the original prescription? Following an initial audit cycle an educational poster was distributed to all clinical staff via email and hard copies of the poster were placed strategically throughout the ward before its effectiveness was measured. RESULTS: During the pre-intervention phase, compliance with all five measures varied from 0 to 25%. There was an increase in the variation in compliance after the poster intervention to 14-44%; however, this masked better overall compliance with all five investigative questions with figures of 44%, 39% and 42% being recorded in three of the four post-intervention days. Overall there was increased compliance with four of the five audit questions. Indeed compliance with question 3 rose from 14% to 83%. CONCLUSIONS: The poster intervention was marginally effective while also showing that students can improve prescribing in a clinical setting. PMID- 24215038 TI - Peri-operative renal morbidity secondary to gentamicin and flucloxacillin chemoprophylaxis for hip and knee arthroplasty. AB - INTRODUCTION: This retrospective cohort study uses serum creatinine levels to assess the effect of gentamicin and flucloxacillin on renal function in hip and knee arthroplasty patients. METHODS: Serum creatinine levels were recorded pre operatively and at two points post-operatively (sample 1 and sample 2) for all patients undergoing hip and knee arthroplasty. Either cefuroxime, or gentamicin and flucloxacillin were used for chemoprophylaxis. The Risk, Injury, Failure, Loss, End Stage classification was used to assess renal injury. RESULTS: The differences in mean percentage change between the two groups were 5.86% (p = 0.077) and 11.34% (p = 0.030) at sample 1 and sample 2, respectively. Two patients (1.62%) receiving cefuroxime were exposed to renal risk or worse at some point. A total of nine patients (6.04%) receiving flucloxacillin and gentamicin were exposed to renal risk. Of these, three (2.01%) sustained renal injury and two (1.34%) sustained renal failure. The risk of being exposed to renal risk was 3.75 times greater for the gentamicin and flucloxacillin group. The risks of sustaining a significant deterioration of renal function were 1.9 and 17 times greater for the gentamicin and flucloxacillin group at the first and second post operative samples, respectively. DISCUSSION: Flucloxacillin and gentamicin significantly worsens renal function post-operatively compared with cefuroxime. PMID- 24215039 TI - The first 100 thrombolysis cases in a novel Scottish mesh telestroke system. AB - Stroke thrombolysis has been a major driver for change within stroke services. However, until recently its widespread application has been limited to tertiary centres. Transfer to tertiary care can lead to significant delays in thrombolysis. We developed a novel mesh telestroke network, which allows stroke specialists to make videoconference-based thrombolysis decisions either from one of three stroke units or from home. We report data on the first 100 patients treated using this model and retrospectively review the first 100 strokes thrombolysed with tissue plasminogen activator across three stroke units. Prospectively collected data were extracted from the Stroke Audit In Lanarkshire database. Case notes were retrieved for clarification when necessary. Outcome measures were timings from symptom onset to infusion, post-thrombolysis symptomatic intracerebral haemorrhage and death. Fifty-one percent of cases were assessed by telestroke link. Median symptom onset to thrombolysis was 160 min (IQR 125-190). There were two symptomatic intracerebral haemorrhages, both in patients assessed face-to-face. Overall mortality was 14%. Our experience of tissue plasminogen activator is comparable to UK data extracted from SITS-MOST in overall timings and complication rates. This model of telemedicine could be replicated to provide safe thrombolysis to areas with challenging infrastructure, geography or insufficient stroke specialist cover. PMID- 24215040 TI - An epidemiological study of the association of coffee with chronic liver disease. AB - BACKGROUND AND AIMS: Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. METHODS AND RESULTS: Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = <0.001). There was no correlation between Child's Pugh (-0.018) and MELD scores (-0.132) with coffee consumption. CONCLUSION: Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed. PMID- 24215041 TI - Total knee replacement in patients with haemophilia: the Scottish experience. AB - INTRODUCTION: Patients with haemophilia commonly develop arthropathy secondary to recurrent haemarthroses. Although modern treatment with replacement coagulation factors has reduced the prevalence of end-stage arthropathy, total joint replacement is still required in a small group of patients. These patients may be at higher risk of complications and the outcome of surgery may not be comparable to reports of outcomes of total joint replacement in the general population. The purpose of this study was to describe the change in function in patients undergoing total knee replacement for haemophilic arthropathy. PATIENTS AND METHODS: Patients undergoing total knee arthroplasty in a tertiary centre had prospective evaluations of patient reported outcome measures and range of movement. Their post-operative function was evaluated in a combined orthopaedic haematology clinic. Eight male patients underwent 13 total knee replacements from 1999 to 2007 and were followed up for a median of 78 months (range 17-116). RESULTS: The median Oxford knee score improved from 45.5 pre-operatively to 28 (p = 0.049). There was a similar improvement in SF-12 physical (p = 0.017) and Knee Society scores (objective p = 0.001; function p = 0.002). Four total knee replacements were performed in patients with inhibitor antibodies and were treated with recombinant activated factor VIIa. These patients had reduced range of movement (p = 0.047). No patients suffered deep infection. CONCLUSIONS: Total knee replacement in patients with haemophiliac arthropathy resulted in improvement in range of movement and function. The presence of factor VIII inhibitors resulted in reduced range of movement, but similar patient reported outcome measures. PMID- 24215042 TI - Antidepressants for mothers: what are psychiatrists prescribing? AB - BACKGROUND AND AIMS: Depressive illness in the perinatal period is common and can be associated with detrimental effects to both mother and child. The evolving evidence base on the safety of antidepressants in pregnancy and breastfeeding can make prescribing decisions challenging. This study aimed to investigate current prescribing practices and attitudes of hospital psychiatrists towards depression in pregnant and breastfeeding mothers. METHODS AND RESULTS: This qualitative survey was conducted by way of e-mail survey to 95 psychiatrists, of all grades and specialities, based within The Royal Edinburgh Hospital. A majority of psychiatrists are choosing and avoiding antidepressants in accordance with the National Institute for Health and Clinical Excellence guidelines. A minority of respondents are selecting classes of antidepressants, which raises concern about the safety of such prescribing decisions. The majority of psychiatrists expressed a lack of confidence when prescribing and expressed a wish for further training in this area. CONCLUSION: This study indicates a degree of uncertainty amongst psychiatrists of all grades when prescribing to these special groups. We would recommend increased training in this area to all psychiatrists and an increased emphasis placed upon incorporating perinatal psychiatry within the postgraduate psychiatric curriculum. PMID- 24215043 TI - Neurology liaison services in the acute medical receiving unit. AB - INTRODUCTION: Guidelines from the Association of British Neurologists and National Health Service Quality Improvement Scotland suggest that neurologists should be involved in the early management of patients presenting to hospital with acute neurological illness. AIM: We chose to evaluate whether regular neurology review in an acute medical receiving unit in a busy city hospital was feasible, and whether it would have an impact on patient care. METHODS: Over a 5 week period from Monday to Friday, all neurology patients admitted to an acute medical receiving unit were identified and all headaches and blackouts were reviewed. RESULTS: Fourteen (24%) were headache patients, 37 (63%) presumed seizure and 8 (13%) had another neurological illness. Diagnosis was made by the admitting physician in six headache patients (43%). The remaining eight headache patients were diagnosed by the visiting neurologist and two physician diagnoses were revised. The diagnosis made by the admitting physician was clarified by the visiting neurologist in 13 blackout patients (35%) and nine other diagnoses were revised (24%). Appropriate outpatient follow-up or transfer was arranged. CONCLUSION: These results suggest that a daily neurology review service is useful in medical receiving units by clarifying diagnoses, directing tests and limiting inappropriate follow-up. PMID- 24215044 TI - Hand-assisted laparoscopic living donor nephrectomy: initial Glasgow experience. AB - AIMS: The study presents the early results of hand-assisted laparoscopic living donor nephrectomy (HALDN) carried out in West of Scotland from June 2009 to October 2010. METHODS: The first 20 HALDN procedures carried out in our unit are presented. The outcomes reported are warm ischaemia time, operative time, delayed graft function, recipient renal function and one-month morbidity and mortality of donor and recipient. SPSS 15.0 was used for statistical analysis. RESULTS: The mean age of the donors was 44 +/- 10 years, predominantly females (n = 13), median operative time 135 +/- 33 min and warm ischaemia time 41 +/- 16 s. The length of the incision used was 65 mm in all cases. Duration of hospital stay was 5 +/- 1 days. Patient mortality was 0 and morbidity minimal with two donors developing minor wound infection and no other clinically significant postoperative morbidity. Among the recipients, 18/20 (90%) transplants worked primarily with two delayed graft functions, one due to early surgical complications in a small paediatric recipient and one due to recipient renal artery thrombosis. CONCLUSION: HALDN is safe and associated with minimal morbidity; further analysis aims to confirm excellent cosmetic results and quick return to activity compared with the standard open nephrectomy technique. PMID- 24215046 TI - Edinburgh, the Scottish pioneers of anatomy and their lasting influence in South Africa. AB - The history of the origin of anatomy education in South Africa is the history of an arduous journey through time. The lasting influence of Edinburgh came in the form of Robert Black Thomson. He was a student and assistant of Sir William Turner who gave rise to the first chair of anatomy and the establishment of a department at the South African College, known today as University of Cape Town. Thomson was later succeeded by Matthew Drennan, a keen anthropologist, who was revered by his students. This Scottish link prevailed over time with the appointment of Edward Philip Stibbe as the chair of anatomy at the South African School of Mines and Technology, which later became the University of the Witwatersrand. Stibbe's successor, Raymond Arthur Dart, a graduate of the University of Sydney, was trained in an anatomy department sculpted on that of Edinburgh by Professor James Thomas Wilson. Wilson's influence at the University of Sydney can be traced back to Edinburgh and William Turner through Thomas Anderson Stuart. Both Dart and Robert Broom, another Scot, were considered as Africa's wild men by the late Professor Tobias. Here, the authors explore the Scottish link and origins of anatomy pedagogy in South Africa. PMID- 24215045 TI - Gentamicin use in neonates: should we have a change of practice? AB - BACKGROUND: Gentamicin, one of the most commonly used antibiotics in neonates, has potential toxicity. This study was performed to determine the incidence of potential toxicity of gentamicin in term and preterm neonates. METHODS: A one year retrospective study in neonates admitted to Special Baby Care Units at University Hospital of North Durham and Darlington Memorial Hospitals. We reviewed each admission and looked through the case notes in detail to document information about gentamicin administration, dosage and elevated gentamicin levels in the blood. Pre-third dose gentamicin levels >2 mg/L were classified as elevated. RESULTS: Overall, 192 babies (83 term and 109 preterm) had documented gentamicin levels. Of these, 43% (84/192) manifested elevated gentamicin levels. Of the babies with elevated gentamicin levels, 67% (56/84) weighed less than 2.5 kg. When a combination of gestation period and weight was considered, 61% (51/84) of preterm infants weighing <2.5 kg had elevated levels whereas only one term infant <2.5 kg exhibited elevated levels. CONCLUSION: Preterm neonates and specifically low birth weight neonates tolerate gentamicin poorly. Dosage and/or interval of administration of the medication may need modification in this group to minimise toxicity. PMID- 24215047 TI - The management of primary hyperparathyroidism. PMID- 24215049 TI - Post-operative cyclizine misuse. AB - Cyclizine is commonly prescribed as an anti-emetic post-operatively. We report a case of a 51-year-old woman who developed addiction to intravenous cyclizine following regular administration at recommended doses. This is the first report of cyclizine misuse post-operatively. We compare this case to cyclizine abuse reported amongst other populations. Prescribers should be aware of the potential of cyclizine as a drug of abuse. PMID- 24215050 TI - Takotsubo cardiomyopathy in chronic infection. AB - INTRODUCTION: Takotsubo cardiomyopathy is the acquired, reversible syndrome characterised by apical ballooning and base hypercontractility and probably precipitated by emotional and physical stressors that cause a hyperadrenergic state. It presents as an acute coronary event without there being coronary disease. CASE PRESENTATION: We present a case of a 73-year-old woman who developed takotsubo cardiomyopathy with concomitant septic shock from a chronic hemiarthroplasty site infection. The prosthesis had been removed, the surgical site drained twice and multiple antibiotics prescribed. She also had a previous episode of sepsis from she recovered with vasopressor support. CONCLUSION: To the author's knowledge, this is the first case of this syndrome occurring in such a prolonged septic process and where the primary focus was a surgical wound. This may indicate continued myocardial injury secondary to a sustained hyperadrenergic state as a possible mechanism for takotsubo cardiomyopathy, rather than a one time catecholamine surge. PMID- 24215051 TI - Treating tuberculosis in the elderly population: a lesson in multi-disciplinary care. AB - INTRODUCTION: It is estimated that the risk of reactivation of previously untreated healed or latent tuberculosis is around 0.04 cases per 100 person years. The incidence of active tuberculosis in Peterborough is 28.0 per 100,000 population compared with 8.3 in the East of England region. The majority of patients are of Indian or Pakistani origin and aged between 15 and 65. CASE PRESENTATION: Here, we present the case of an 88-year-old gentleman who successfully completed anti-tuberculous therapy for smear-negative tuberculosis and discuss some of the issues encountered in his management, with particular emphasis on drug surveillance, tolerance of anti-tuberculous therapy and drug interactions. CONCLUSION: Elderly persons presenting with tuberculosis are more likely to present atypically and may need a staged initiation of therapy with continued pharmacist advice, due to high risk of interactions. PMID- 24215052 TI - Langerhans cell sarcoma of the nasopharynx: a rare case. AB - Langerhans cell sarcoma, a tumour with markedly malignant cytological features that originates from Langerhans cells, is a very rare disease. We report the first case of 39-year-old male with Langerhans cell sarcoma arising in the nasopharynx. We chose the 2-chlorodeoxyadenosine (2-CDA) regimen as first-line chemotherapy, and clinical improvement of Langerhans cell sarcoma was obtained. After the fourth cycle of 2-CDA therapy, however, disease progression was observed, and we administered ESHAP regimen (etoposide, carboplatin, cytarabine, methylprednisolone) as a second-line therapy. After we administered two cycles of ESHAP, however, the patient developed aggressive progression and he died. The importance of immunohistochemical findings is obvious in Langerhans cell sarcoma diagnosis. Considering that Langerhans cell sarcoma behaves in a very malignant fashion, a more aggressive treatment approach is necessary for patients with Langerhans cell sarcoma. PMID- 24215053 TI - Massive atrial myxoma: surgical treatment for an incidentaloma causing dyspnoea. AB - A patient presented having a one-week history of recurrent falls and confusion and weight loss over an unspecified period of time. A chest radiograph revealed bilateral pleural effusions and the patient was treated for community acquired pneumonia. His weight loss and suspicion of malignant disease prompted computer tomography to be conducted. This revealed widespread mediastinal and oesophageal adenopathy. An echocardiogram showed a large hyperechoic mobile mass. Coronary angiography showed complete occlusion of the left anterior descending and right coronary arteries. He underwent two-vessel coronary artery bypass grafting and an atriotomy to excise the myxoma. He experienced no operative complications and no neurological deterioration and was discharged home three weeks later in sinus rhythm. Myxomas can duplicate a broad array of cardiorespiratory symptoms and signs and can often escape detection by being picked up as an incidentaloma. PMID- 24215054 TI - Orofacial granulomatosis related to amalgam fillings. AB - This paper reports on a case of Orofacial Granulomatosis (OFG) in which the presence of amalgam fillings appears to have played a part in the aetiology. Once these restorations were removed and replaced with an alternative composite restorative material, all symptoms and signs of OFG resolved completely. This case highlights the necessity to include dental metals in the patch test battery when performing delayed patch testing on patients with OFG. PMID- 24215055 TI - Large solitary fibrous tumour of the retroperitoneum: a case report and review of the literature. AB - INTRODUCTION: This report describes an unusual case of a large solitary fibrous tumour (SFT) arising in the retroperitoneum. CASE PRESENTATION: A 53-year-old woman presented at the Emergency Department with urinary retention and lumbar pain. The urological examination was negative, whereas a presacral retroperitoneal mass was disclosed on ultrasound. The laboratory studies, including tumour markers, were negative. On laparotomy, it was not possible to remove the mass completely due to the difficulty of dissecting it free of the sacrum. Grossly, the fragment had a yellowish-white surface, with areas of necrosis and haemorrhage. On immunohistochemistry, tumour cells were positive for CD34, CD99 and Bcl-2 and negative for CD45, synaptophysin, chromogranin, S100, neuron-specific enolase, CK AE1-AE3, CK7, Wilms' tumour 1, smooth muscle actin, factor VIII, myogenin, epithelial membrane antigen, thyroid transcription factor 1 and CD117, leading to a diagnosis of SFT. Molecular investigation ruled out synovial sarcoma. CONCLUSION: Although SFT usually has a favourable prognosis, close follow-up is recommended due to the limited information on its long-term behaviour. PMID- 24215056 TI - Intentional overdose of azathioprine in a patient with systemic lupus erythematosus. AB - A 14-year-old girl with systemic lupus erythematosus presented with a mixed overdose of paracetamol, ibuprofen and azathioprine (1500 mg) following a deliberate self-harm attempt. The patient was admitted and monitored. No adverse effects were observed. A review of the literature showed very few reported azathioprine overdoses. Lupus patients are at risk of developing low mood and depression (and related self-harm including overdose of medication). This can be as a consequence of the disease process itself or in reaction to the stresses of living with a chronic disease, which are perhaps particularly acute in some adolescents with the disease. An intentional overdose in a patient with lupus is clearly a cry for help and should be appropriately managed. Counselling of young people and their parents about possible mood disorders is an important part of the management of this chronic disease. Despite the theoretical risk of significant myelosuppression as well as other potential adverse effects, azathioprine in acute overdose seems to be generally well tolerated. PMID- 24215057 TI - Cavernous haemangioma of the testis mimicking testicular malignancy in an adolescent. AB - Haemangioma of the testis is a rare condition. This benign vascular neoplasm may arise either within the testicular parenchyma (intratesticular) as in this case or from adnexal structures of the testis (extratesticular). Intratesticular haemangioma is rarer than extratesticular form. Intratesticular vascular neoplasms are extremely rare tumours and mostly seen in children or young adults. There are 21 reported testicular haemangioma cases in the literature as indexed in PubMed. Since 2007, only 19 cases of cavernous haemangioma have been reported in the literature in PubMed and other indexed sites. We report a case of cavernous haemangioma of the testis to attract attention to testicular haemangioma and also to prevent invasive surgery of the testis. PMID- 24215058 TI - Massive mesenteric and portal venous thrombosis secondary to hormone replacement therapy. AB - Hormone replacement therapy increases risk of deep venous thrombosis (DVT) mainly in the extremities and lungs. There are reports of mesenteric ischemia secondary to oral contraceptive pills but no reports on hormone replacement therapy and mesenteric thrombosis. The authors present a case of a 44-year-old obese (BMI 32) woman, on long-term hormone replacement therapy, presented with thrombosis of portal, splenic and superior mesenteric veins. She underwent surgical resection of ischemic bowel and planned re-look laparotomies with further resections and jejuno-ileal anastomosis at final laparotomy. Thorough haematological investigations were normal. The authors conclude that hormone replacement therapy in obese patients with no other risk factors can cause a catastrophic mesenteric thrombosis. Aggressive surgical resection with re-look laparotomies and further resections can be lifesaving. PMID- 24215059 TI - Comparative impact of genetically modified and non modified maize (Zea mays L.) on succeeding crop and associated weed. AB - This research work documents the comparative impact of genetically modified (GM) (insect resistance) and non modified maize (Zea mays L.) on growth and germination of succeeding crop wheat (Triticum aestivum L.) and associated weed (Avena fatua L.). The aqueous extracts of both the GM and non-GM maize exhibited higher phenolic content than that of methanolic extracts. Germination percentage and germination index of wheat was significantly decreased by GM methanolic extract (10%) as well as that of non-GM maize at 3% aqueous extract. Similarly germination percentage of weed (Avena fatua L.) was significantly reduced by application of 3% and 5% methanolic GM extracts. All extracts of GM maize showed non-significant effect on the number of roots, root length and shoot length per plant but 5% and 10% methanolic extracts of non-GM maize significantly increased the number of roots per plant of wheat seedling. Similarly, 10% methanolic extract of GM maize significantly increased the number of roots per plant of weed seedling. Methanolic extracts of GM and non-GM maize (3% and 5%) significantly decreased the protease activity in wheat as compared to untreated control. PMID- 24215060 TI - Investigation of cytotoxic, genotoxic and oxidative properties of carvacrol in human blood cells. AB - Carvacrol (CVC), a major constituent of genera Origanum and Thymus, is such a substance that has attracted attention because of its wide variety of beneficial biological activities such as antibacterial, antifungal, and anticancer effects. However, there are limited data on the cytogenetic and antioxidant effects of CVC in cultured human blood cells. The aim of this study was to investigate for the first time the genetic, oxidative, and cytotoxic effects of CVC in cultured human blood cells (n= 5). Human blood cells were treated with CVC (0-200 mg/L) for 24 and 48 h and then cytotoxicity detected by lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine the oxidative effects. The results of LDH and MTT assays showed that CVC (at concentrations above 100 mg/L) decreased cell viability. In our in vitro test systems, it was observed that CVC had no mutagenic effects on human lymphocytes. On the other hand, CVC (at 50, 75, and 100 mg/L) treatment caused statistically important (p< 0.05) increases in TAC and TOS levels (at 150 and 200 mg/L) on human lymphocytes. In conclusion, CVC can be a new resource of therapeutics as recognized in this study with their nonmutagenic and antioxidant features. PMID- 24215061 TI - Antispasmodic and antidiarrheal activities of rhizomes of Polygonatum verticillatum maneuvered predominately through activation of K+ channels: Components identification through TLC. AB - Polygonatum verticillatum has traditionally been used for various purposes. The present study was aimed to validate the antispasmodic and antidiarrheal properties of crude methanolic extract of rhizomes of P. verticillatum (PR). Isolated rabbit jejunum preparations were suspended in tissue baths to measure the isotonic responses using Power Lab data acquisition system for the antispasmodic activity of PR, while the antidiarrheal activity was conducted in vivo in mice. PR caused complete relaxation of the spontaneous contractions of isolated rabbit jejunum preparations in a dose-dependent mode. A complete inhibition was observed against low potassium (K(+); 25 mM)-induced contractions, while the plant extract partially inhibited the high K(+)(80 mM)-induced contractions. From a mechanistic point of view, the spasmolytic effect of PR against low K(+)was antagonized by glibenclamide similar to the effect of cromakalim, thus showing the presence of constituents in PR mediating spasmolytic activity predominantly through the activation of adenosine triphosphate-sensitive K(+)channels. When tested against castor oil-induced diarrhea in mice, oral administration of the plant extract manifested marked antidiarrheal activity at the doses of 500 and 1000 mg/kg similar to loperamide. This study provided a pharmacological basis for the medicinal use of PR in abdominal colic and diarrhea. PMID- 24215062 TI - Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8 tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels. AB - This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 ug/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor alpha and interleukin 1beta levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD. PMID- 24215063 TI - Alterations in the fatty acid profile, antioxidant enzymes and protein pattern of Biomphalaria alexandrina snails exposed to the pesticides diazinon and profenfos. AB - The use of pesticides is widespread in agricultural activities. These pesticides may contaminate the irrigation and drainage systems during agriculture activities and pests' control and then negatively affect the biotic and a biotic component of the polluted water courses. The present study aimed to evaluate the effect of the pesticides diazinon and profenfos on some biological activities of Biomphalaria alexandrina snails such as fatty acid profile, some antioxidant enzymes (thioredoxin reductase (TrxR), sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) as well as glutathione reductase (GR) and lipid peroxidation (LP)) and protein patterns in snails' tissues exposed for 4 weeks to LC10 of diazinon and profenfos. The results showed that the two pesticides caused considerable reduction in survival rates and egg production of treated snails. Identification of fatty acid composition in snail tissues treated with diazinon and profenfos pesticides was carried out using gas-liquid chromatography (GLC). The results declared alteration in fatty acid profile, fluctuation in percentage of long chain and short chain fatty acid contributions either saturated or unsaturated ones, and a decrease in total lipid content in tissues of snails treated with these pesticides. The data demonstrate that there was a significant inhibition in the activities of tissues SOD, CAT, glutathione reductase (GR), TrxR, and SDH in tissues of treated snails, while a significant elevation was detected in LP as compared to the normal control. On the other hand, the electrophoretic pattern of total protein showed differences in number and molecular weights of protein bands due to the treatment of snails. It was concluded that the residues of diazinon and profenfos pesticides in aquatic environments have toxic effects onB. alexandrina snails. PMID- 24215064 TI - Comet assay with gill cells of Mytilus galloprovincialis end point tools for biomonitoring of water antibiotic contamination: Biological treatment is a reliable process for detoxification. AB - This article investigates the ability of Pseudomonas peli to treat industrial pharmaceuticals wastewater (PW). Liquid chromatography-mass spectrometry (MS)/MS analysis revealed the presence, in this PW, of a variety of antibiotics such as sulfathiazole, sulfamoxole, norfloxacine, cloxacilline, doxycycline, and cefquinome.P. peli was very effective to be grown in PW and inducts a remarkable increase in chemical oxygen demand and biochemical oxygen demand (140.31 and 148.51%, respectively). On the other hand, genotoxicity of the studied effluent, before and after 24 h of shaking incubation with P. peli, was evaluated in vivo in the Mediterranean wild mussels Mytilus galloprovincialis using comet assay for quantification of DNA fragmentation. Results show that PW exhibited a statistically significant (p< 0.001) genotoxic effect in a dose-dependent manner; indeed, the percentage of genotoxicity was 122.6 and 49.5% after exposure to 0.66 ml/kg body weight (b.w.); 0.33 ml/kg b.w. of PW, respectively. However, genotoxicity decreased strongly when tested with the PW obtained after incubation with P. peli We can conclude that using comet assay genotoxicity end points are useful tools to biomonitor the physicochemical and biological quality of water. Also, it could be concluded that P. peli can treat and detoxify the studied PW. PMID- 24215065 TI - Cytotoxic effect of chlorpyrifos ethyl and its degradation derivatives by Pseudomonas peli strain isolated from the Oued Hamdoun River (Tunisia). AB - A bacterium was isolated from the river of Oued Hamdoun (Tunisia), and its phenotypic features, physiological and chemotaxonomic characteristics and phylogenetic analysis of 16S ribosomal RNA sequence revealed it as Pseudomonas peli (P. peli). Chlorpyrifos ethyl (CP) was used as the sole source of carbon and energy by P. peli, and it was cometabolised in the presence of glucose. CP was completely degraded by P. peli after 96 h of shake incubation. High-performance liquid chromatography analysis indicated that the biodegradation kinetics was not affected by the addition of glucose into the culture medium. In the present study, only transient accumulation of one major no-identified product was observed after 48 h of incubation, with no other persistent metabolites detected. Cytotoxicity of CP, before and after biodegradation with P. peli, was evaluated in vitro using the MTT-colorimetric assay against three human cancer cell lines (A549, lung cell carcinoma, HT29, colon adenocarcinoma and MCF7, breast adenocarcinoma). CP reduced viability of all human cell lines in a dose-dependent manner. Its activity was very remarkable against A549 cell line. However, cytotoxicity strongly decreased in CP obtained after incubation with P. peli Hence, we conclude that when incubated under appropriate conditions,P. peli has a metabolism that completely detoxifies CP. PMID- 24215066 TI - Studies on fate and toxicity of nanoalumina in male albino rats: Some haematological, biochemical and histological aspects. AB - The work aimed to evaluate the nanoalumina toxicity on the histological architecture, some haematological and biochemical aspects in male albino rats, during acute and sublethal experiments. Rats, in acute experiments, were injected with a single-acute dose of 3.9 g or 6.4 g or 8.5 g of aluminium oxide (Al2O3) kg(-) (1), whereas those of sublethal were injected with 1.3 g of Al2O3 kg(-) (1)2 days(-) (1) One-way analysis of variance indicated that injected doses and the experimental periods were significantly affected by haemoglobin (Hb) content; haematocrit value (Hct); white blood cell (WBC) count; blood platelet (Plt) count; mean corpuscular volume (MCV); mean corpuscular Hb (MCH) and MCH concentration (MCHC). In acute experiments, Hct, WBC count, MCV and Plt were significantly higher than the corresponding controls, whereas Hb, MCH and MCHC markedly decreased. In comparison with the related controls after 1, 3 and 7 days post-injection, red blood cell count, Hb, Hct, WBC count, Plt and MCV were significantly increased, but begun to decrease after 14 or/and 28 days and were associated with a marked decrease in MCH and MCHC. In serum of rats injected with acute or sublethal dose, the concentrations of total protein (TP) and total lipid (TL) were significantly lesser than the corresponding controls, whereas the levels of urea, uric acid, creatinine and the activities of aspartate aminotransferase and alanine aminotransferase were markedly increased. The injected doses were directly proportional with all the studied biochemical parameter, except the TL and TP that exhibited a negative correlation. Histologically, the highest acute and sublethal doses of nanoalumina caused hepatic irregular disarray, necrosis to the hepatic and Kupffer cells that are associated with congested blood sinusoids. The renal tissues characterized by the appearance of inter-tubular congestion that is accompanied by the dilation of the vascular glomeruli that completely occupied Bowman's capsule and accompanied with partial disappearance of the renal tubule's brush border. The brain showed a progressive degeneration of neurons in both the experiments. PMID- 24215067 TI - Protective effects of ethyl acetate fraction of Lawsonia inermis fruits extract against carbon tetrachloride-induced oxidative damage in rat liver. AB - This study aimed to investigate the antioxidant properties of different fractions obtained from the fruits of Lawsonia inermis, a widely used medicinal plant, against carbon tetrachloride (CCl4)-induced oxidative stress in rat liver. The results show that several fractions obtained from L. inermis fruits possessed important antioxidant activity. Among them, the ethyl acetate (EA) fraction showed the highest antioxidant activity. Then, EA fraction was selected for the purification of potential antioxidant compounds. The hepatoprotective effects of EA fraction and its most active constituent, gallic acid (GA), were evaluated against CCl4-induced hepatotoxicity in rats. CCl4 induced oxidative stress by a significant rise in serum marker enzymes. However, pretreatment of rats with EA fraction of fruits of L. inermis at a dose of 250 mg kg(-1)body weight and GA significantly lowered some serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase) in treated rats. A significant reduction in hepatic thiobarbituric acid reactive substances and an increase in antioxidant enzymes namely superoxide dismutase, catalase, and glutathione peroxidase by treatment with plant extract and GA, against CCl4-treated rats, were observed. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular necrosis, vacuolization, and inflammatory cell infiltration. This potential antioxidant activity is comparable to those of the major purified antioxidant compound, GA. Based on these results, it was observed that fruits of L. inermis protect liver from oxidative stress induced by CCl4 and thus help in evaluation of traditional claim on this plant. PMID- 24215068 TI - The endocrine disruptor effect of the herbicides atrazine and glyphosate on Biomphalaria alexandrina snails. AB - Atrazine (AZ) and glyphosate (GL) are herbicides that are widely applied to cereal crops in Egypt. The present study was designed to investigate the response of the snailBiomphalaria alexandrina(Mollusca: Gastropoda) as a bioindicator for endocrine disrupters in terms of steroid levels (testosterone (T) and 17beta estradiol (E)), alteration of microsomal CYP4501B1-like immunoreactivity, total protein (TP) level, and gonadal structure after exposure to sublethal concentrations of AZ or GL for 3 weeks. In order to study the ability of the snails' recuperation, the exposed snails were subjected to a recovery period for 2 weeks. The results showed that the level of T, E, and TP contents were significantly decreased (p <= 0.05) in both AZ- and GL-exposed groups compared with control (unexposed) group. The level of microsomal CYP4501B1-like immunoreactivity increased significantly (p <= 0.05) in GL- and AZ-exposed snails and reach nearly a 50% increase in AZ-exposed group. Histological investigation of the ovotestis showed that AZ and GL caused degenerative changes including azoospermia and oocytes deformation. Interestingly, all the recovered groups did not return back to their normal state. It can be concluded that both herbicides are endocrine disrupters and cause cellular toxicity indicated by the decrease of protein content and the increase in CYP4501B1-like immunoreactivity. This toxicity is irreversible and the snail is not able to recover its normal state. The fluctuation of CYP4501B1 suggests that this vertebrate-like enzyme may be functional also in the snail and may be used as a biomarker for insecticide toxicity. PMID- 24215069 TI - Cholesterol depletion inhibits epidermal growth factor receptor transactivation by angiotensin II in vascular smooth muscle cells. Role of cholesterol-rich microdomains and focal adhesions in angiotensin II signaling. PMID- 24215073 TI - A Nobel Prize for membrane traffic: vesicles find their journey's end. AB - Cell biologists everywhere rejoiced when this year's Nobel Prize in Physiology or Medicine was awarded to James Rothman, Randy Schekman, and Thomas Sudhof for their contributions to uncovering the mechanisms governing vesicular transport. In this article, we highlight their achievements and also pay tribute to the pioneering scientists before them who set the stage for their remarkable discoveries. PMID- 24215077 TI - Auxin and the ubiquitin pathway. Two players-one target: the cell cycle in action. AB - Plants are sessile organisms that have to adapt their growth to the surrounding environment. Concomitant with this adaptation capability, they have adopted a post-embryonic development characterized by continuous growth and differentiation abilities. Constant growth is based on the potential of stem cells to divide almost incessantly and on a precise balance between cell division and cell differentiation. This balance is influenced by environmental conditions and by the genetic information of the cell. Among the internal cues, the cross-talk between different hormonal signalling pathways is essential to control this division/differentiation equilibrium. Auxin, one of the most important plant hormones, regulates cell division and differentiation, among many other processes. Amazing advances in auxin signal transduction at the molecular level have been reported, but how this signalling is connected to the cell cycle is, so far, not well known. Auxin signalling involves the auxin-dependent degradation of transcription repressors by F-box-containing E3 ligases of ubiquitin. Recently, SKP2A, another F-box protein, was shown to bind auxin and to target cell-cycle repressors for proteolysis, representing a novel mechanism that links auxin to cell division. In this review, a general vision of what is already known and the most recent advances on how auxin signalling connects to cell division and the role of the ubiquitin pathway in plant cell cycle will be covered. PMID- 24215076 TI - Comprehensive insights on how 2,4-dichlorophenoxyacetic acid retards senescence in post-harvest citrus fruits using transcriptomic and proteomic approaches. AB - Auxin-like 2,4-dichlorophenoxyacetic acid (2,4-D), a high-efficiency anti stalling agent for the post-harvest fresh fruit industry, has had its use restricted due to environmental concerns. However, no other substitutes for 2,4-D are available to the post-harvest industry. Insights into the molecular mechanism underlying the effects of 2,4-D on fruit quality preservation will provide a theoretical basis for exploring new safe and effective anti-stalling agents. This study comprehensively analysed changes in the peel of Olinda Valencia orange [Citrus sinensis (L.) Osbeck] induced by 500 ppm 2,4-D using 'omic'-driven approaches. Transcriptional profiling revealed that transcriptional factor (mainly AP2/ERF, WRKY, and NAC family members), transport, and hormone metabolism genes were over-represented and up-regulated within 24h post-treatment (HPT). Stress defence genes were up-regulated, while cell wall metabolism genes were down-regulated after 48 HPT. However, secondary metabolism genes, especially phenylpropanoid and lignin biosynthesis-related genes, were over-represented at all the time points. Comparative proteomic analysis indicated that the expression of proteins implicated in stress responses (25%), hormone metabolism, and signal transduction (12%) significantly accumulated at the post-transcriptional level. Hormone levels detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) showed that abscisic acid, salicylic acid, and 2,4-D significantly increased, while ethylene production (detected by gas chromatography) decreased after 2,4-D treatment. In addition, lignin and water content in the fruit peel also increased and the epicuticle wax ultrastructure was modified. In conclusion, 2,4-D retarded fruit senescence by altering the levels of many endogenous hormones and by improving stress defence capabilities by up-regulating defence-related genes and proteins. PMID- 24215078 TI - Evidence of positive selection for a glycogen synthase (GYS1) mutation in domestic horse populations. AB - A dominantly inherited gain-of-function mutation in the glycogen synthase (GYS1) gene, resulting in excess skeletal muscle glycogen, has been identified in more than 30 horse breeds. This mutation is associated with the disease Equine Polysaccharide Storage Myopathy Type 1, yet persists at high frequency in some breeds. Under historical conditions of daily work and limited feed, excess muscle glycogen may have been advantageous, driving the increase in frequency of this allele. Fine-scale DNA sequencing in 80 horses and genotype assays in 279 horses revealed a paucity of haplotypes carrying the mutant allele when compared with the wild-type allele. Additionally, we found increased linkage disequilibrium, measured by relative extended haplotype homozygosity, in haplotypes carrying the mutation compared with haplotypes carrying the wild-type allele. Coalescent simulations of Belgian horse populations demonstrated that the high frequency and extended haplotype associated with the GYS1 mutation were unlikely to have arisen under neutrality or due to population demography. In contrast, in Quarter Horses, elevated relative extended haplotype homozygosity was associated with multiple haplotypes and may be the result of recent population expansion or a popular sire effect. These data suggest that the GYS1 mutation underwent historical selection in the Belgian, but not in the Quarter Horse. PMID- 24215080 TI - Benefits of surgical incision management now available to more patients. PMID- 24215079 TI - ISSFAL editorial (PLEFA). PMID- 24215081 TI - Reply: To PMID 23121116. PMID- 24215082 TI - Reply: To PMID 23346992. PMID- 24215083 TI - Economic rewards for blood donation: validity of the donor questionnaire as litmus test. PMID- 24215084 TI - Education and Imaging. Gastrointesinal: colonic amyloidosis causing submucosal haematoma and bleeding from straining. PMID- 24215085 TI - Education and Imaging. Gastrointestinal: gastric hemangiopericytoma: an unusual cause of upper gastrointestinal bleeding. PMID- 24215086 TI - Education and Imaging. Hepatobiliary and pancreatic: adenomyomatosis of the gallbladder. PMID- 24215087 TI - Retraction. PMID- 24215089 TI - [Commentary on "Early repolarization pattern and risk for arrhythmia death. A meta-analysis"]. PMID- 24215088 TI - [Therapeutic guidelines on ulcerative colitis: a GRADE methodology based effort of GETECCU]. PMID- 24215090 TI - Steering clear? Few systems have signed up to be 'navigators'. PMID- 24215091 TI - Premier's strong performance. Shares up 17% on second day of trading. PMID- 24215092 TI - Preparing for PrEP. PMID- 24215093 TI - Hospitals say outpatient list prices irrelevant. Insurers, consumer groups could leverage latest CMS data for better deals. PMID- 24215094 TI - On the defense. AHA says most mergers aren't anti-competitive. PMID- 24215095 TI - Evaluation of anti-epileptic property of Marsilea quadrifolia Linn. in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy. AB - OBJECTIVE: To study the anti-epileptic effects of methanolic extract of Marsilea quadrifolia Linn. (MQ) in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced rat models of epilepsy. METHOD: A total of 84 adult male Wistar rats were used. An acute oral toxicity study was conducted on 36 rats and the remaining were used for other experiments. Each model had 24 rats which were allotted into four groups (n = 6). Group I (Control) received 1% carboxymethyl cellulose solution, Group II (Positive control) received phenytoin 300 mg kg(-1) b.w. in the MES model; sodium valproate 200 mg kg(-1) b.w. in the PTZ model, Group III (MQ) received 400 mg kg(-1) b.w. MQ extract and Group IV (MQ) received 600 mg kg( 1) b.w. MQ extract. Hind limb extension (HLE) time and recovery time were noted in the MES model. Latency for myoclonic jerk, seizures and EEG was recorded in the PTZ model. RESULTS: When compared to control, the phenytoin received group did not show HLE. In MQ pre-treated groups only 50% of rats showed HLE. Sodium valproate and various doses of MQ significantly increased the latency for onset of clonus and seizures. PTZ-induced EEG alterations were significantly attenuated by MQ administration and this was comparable to that of the sodium valproate effect. CONCLUSION: Marsilea quadrifolia Linn. showed significant anti-epileptic efficacy against various epilepsy models. PMID- 24215096 TI - Near-infrared colorimetric and fluorescent Cu(2+) sensors based on indoline benzothiadiazole derivatives via formation of radical cations. AB - The donor-acceptor system of indoline-benzothiadiazole is established as the novel and reactive platform for generating amine radical cations with the interaction of Cu(2+), which has been successfully exploited as the building block to be highly sensitive and selective near infrared (NIR) colorimetric and fluorescent Cu(2+) sensors. Upon the addition of Cu(2+), an instantaneous red shift of absorption spectra as well as the quenched NIR fluorescence of the substrates is observed. The feasibility and validity of the radical cation generation are confirmed by cyclic voltammetry and electron paramagnetic resonance spectra. Moreover, the introduction of an aldehyde group extends the electron spin density and changes the charge distribution. Our system demonstrates the large scope and diversity in terms of activation mechanism, response time, and property control in the design of Cu(2+) sensors. PMID- 24215097 TI - Update: repeat DWI offenders involvement in fatal crashes in 2010. AB - OBJECTIVE: This analysis is an update of a Traffic Tech published by the National Highway Traffic Safety Administration (NHTSA) in March 1992. Drivers with prior driving-while-intoxicated (DWI) convictions are overrepresented in fatal crashes and the relative risk of fatal crash involvement is greater for these repeat DWI offenders. METHODS: Although it is estimated that 2.1 percent of licensed drivers had a prior arrest for DWI within the past 3 years in 2010, 8.0 percent of intoxicated drivers (blood alcohol concentration [BAC] >= 0.08 g/dL) involved in fatal crashes had at least one prior DWI conviction in the past 3 years during that same year. RESULTS: Drivers with prior DWI convictions are overrepresented in fatal crashes by a factor of 1.62 or are 62 percent more likely to be in a fatal crash. Similarly, drivers with prior DWI convictions are also overrepresented as drinking drivers in fatal crashes: those with low BACs (0.01 0.07) by a factor of 2.38 and those with high BACs (0.08+) by a factor of 3.81. CONCLUSION: Though repeat DWI offenders are at a substantially higher risk of fatal crash involvement, the vast majority of intoxicated drivers in fatal crashes do not have a DWI conviction in the past 3 years (11 out of 12) according to the Fatality Analysis Reporting System records for the year 2010. PMID- 24215099 TI - Electrically driven tuning of the dielectric constant in MoS2 layers. AB - The properties of two-dimensional materials, such as molybdenum disulfide, will play an important role in the design of the next generation of electronic devices. Many of those properties are determined by the dielectric constant which is one of the fundamental quantities used to characterize conductivity, refractive index, charge screening, and capacitance. We predict that the effective dielectric constant (epsilon) of few-layer MoS2 is tunable by an external electric field (Eext). Through first-principles electronic structure calculations, including van der Waals interactions, we show that at low fields (Eext < 0.01 V/A) epsilon assumes a nearly constant value ~4 but increases at higher fields to values that depend on the layer thickness. The thicker the structure, the stronger the modulation of epsilon with the electric field. Increasing of the external field perpendicular to the dichalcogenide layers beyond a critical value can drive the system to an unstable state where the layers are weakly coupled and can be easily separated. The observed dependence of epsilon on the external field is due to charge polarization driven by the bias. Implications on the optical properties as well as on the electronic excitations are also considered. Our results point to a promising way of understanding and controlling the screening properties of MoS2 through external electric fields. PMID- 24215098 TI - Toxicity and pharmacokinetics of intrastromal injection of amphotericin B in a rabbit model. AB - PURPOSE: To investigate the ocular toxicity and pharmacokinetics of intrastromal injection of amphotericin B (AmB) in a rabbit model. METHODS: Forty albino rabbits were randomly divided into five groups (eight per group). The rabbits were anesthetized before they received the medication. Intrastromal injection of 0.1 ml balanced salt solution containing 0, 5, 10, 20 or 30 MUg of AmB was performed on eyes of each group five times (once per four days), respectively. The presence of possible corneal clouding, epithelial erosion and corneal neovascularization was monitored with a slit-lamp biomicroscope. Corneal ultrasonic pachymetry was used to detect the corneal thickness of intrastromal injected eyes. Thirty days after the last injection, the corneal transparency as well as the number and ultrastucture of corneal endothelial cells were examined. The concentrations of the AmB in the cornea and aqueous humor were evaluated at 30 min, 6 h and at 1, 3 and 7 days after the intrastromal injection of 10 ug AmB. RESULTS: Intrastromal injection of AmB at concentrations of 5 and 10 MUg per 0.1 ml did not induce obvious toxicity to the cornea when compared with the controls. However, when the concentration of AmB increased to 20 MUg per 0.1 ml or more, corneal edema, corneal epithelial erosion and severe neovascularization appeared. A single intrastromal injection of 10 MUg AmB achieved an effective drug level in corneas which was maintained for up to 7 days. CONCLUSIONS: Intrastromal injection of AmB at a concentration of less than 10 MUg per 0.1 ml is safe to the rabbit corneas. Intrastromal injection of AmB may be an adjunctive treatment for deep recalcitrant fungal keratitis. PMID- 24215100 TI - Ligand- and structure-based virtual screening for clathrodin-derived human voltage-gated sodium channel modulators. AB - Voltage-gated sodium channels (VGSC) are attractive targets for drug discovery because of the broad therapeutic potential of their modulators. On the basis of the structure of marine alkaloid clathrodin, we have recently discovered novel subtype-selective VGSC modulators I and II that were used as starting points for two different ligand-based virtual screening approaches for discovery of novel VGSC modulators. Similarity searching in the ZINC database of drug-like compounds based on compound I resulted in five state-dependent Na(v)1.3 and Na(v)1.7 modulators with improved activity compared to I (IC50 < 20 MUM). Compounds 2 and 16 that blocked sodium permeation in Na(v)1.7 with IC50 values of 7 and 9 MUM, respectively, are among the most potent clathrodin analogs discovered so far. In the case of compound II, 3D similarity searching in the same database was followed by docking of an enriched compound library into our human Na(v)1.4 open pore homology model. Although some of the selected compounds, e.g., 31 and 32 displayed 21% and 22% inactivated state I(peak) block of Na(v)1.4 at 10 MUM, respectively, none showed better Na(v)1.4 modulatory activity than compound II. Taken together, virtual screening yielded compounds 2 and 16, which represent novel scaffolds for the discovery of human Na(v)1.7 modulators. PMID- 24215103 TI - Humiliation as an intense emotional experience: evidence from the electro encephalogram. AB - Humiliation, the emotion associated with being lowered in status in the eyes of others, seems to be very intense. As such, humiliation has been implied to play an important role in the escalation of inter-individual and inter-group conflict. Here, we provide the first clear empirical evidence that humiliation is indeed a very intense experience. Based on the electro-encephalogram recorded from people reading scenarios that evoked humiliation, anger, or happiness, electrophysiological measures of cognitive intensity were derived for each of the emotion types. The late positive potential (LPP), a measure of the level of perceived (negative), affect was markedly increased in humiliation scenarios compared to happiness and anger scenarios. In addition, event-related desynchronization (ERD) in the alpha-frequency range, a measure of the overall intensity of cortical activation, was significantly more pronounced for humiliation than for happiness and anger scenarios. Our findings support the idea that humiliation is a particularly intense experience that is likely to have far reaching consequences. PMID- 24215101 TI - Association between hemoglobin levels and arterial stiffness for general Japanese population in relation to body mass index status: The Nagasaki Islands study. AB - AIM: To investigate associations between hemoglobin levels and arterial stiffness accounting for body mass index (BMI) in a large-scale cross-sectional study. METHODS: We investigated the association between hemoglobin levels and atherosclerosis evaluated by cardio-ankle vascular index (CAVI), which can assess arterial stiffness independently from blood pressure, while taking BMI status into account. Separate models were constructed for participants with or without anemia. In our main investigation for the association between hemoglobin levels and increased arterial stiffness, only participants without anemia (1064 men and 1886 women) were included to avoid the influence of chronic disease. RESULTS: We found significantly positive associations between increased arterial stiffness and hemoglobin levels for both men and women, and that such associations were limited to subjects with BMI <25 kg/m(2) . The multivariable-adjusted odds ratios (OR) and 95% coincidence intervals (CI) of 1-standard deviation increments in hemoglobin levels for increased arterial stiffness were 1.17 (95% CI 1.00-1.38) for men and 1.17 (95% CI1.02-1.34) for women. For participants with BMI <25 kg/m(2) , the corresponding values were 1.40 (95% CI 1.14-1.73) and 1.19 (95% CI 1.02-1.40), and for those with BMI >=25 kg/m(2) , they were 0.88 (95% CI 0.67 1.15) and 1.12 (95% CI 0.86-1.46). CONCLUSIONS: Independent positive associations between hemoglobin levels and increased arterial stiffness were observed both for Japanese men and women, and those associations were limited to participants with BMI <25 kg/m(2) . PMID- 24215104 TI - Erectile dysfunction in patients with chronic viral hepatitis: a systematic review of the literature. AB - INTRODUCTION: This article reviews the literature on epidemiology and pathogenetic factors of erectile dysfunction in patients with chronic viral hepatic (CVH) diseases in men and the potential implications for diagnosis and treatment. AREAS COVERED: A search to identify original articles, reviews and any other article suitable for the purposes of this review was conducted by combining the following terms: erectile dysfunction and/or sexual dysfunction, chronic viral hepatitis, hepatitis B virus infection and hepatitis C virus infection. EXPERT OPINION: The results of this review have led to the following main observations: i) there is scarce documentation on the association between CVH and sexual dysfunction; ii) hormonal impairment seems to be a major component in the development of erectile dysfunction in CVH; however, published evidence concerning the contribution of other pathogenetic factors is rare and inconclusive and iii) available treatment options for CVH potentially contribute to the development of sexual dysfunction in these patients. Due to the scarce body of evidence, more research is needed to better clarify the mechanisms underlying the association between CVH and sexual dysfunction, the impact of therapy and associated comorbidities on sexual dysfunction and the role of pharmacological treatments in the management of these patients. PMID- 24215105 TI - Muscle force distribution during forward and backward locomotion. AB - Backward walking (BW) is a common technique employed in the treatment of a variety of orthopedic and neurological diseases. BW training may offer some benefits especially in balance and motor control ability beyond those experienced through forward walking (FW). The purpose of this study was to determine whether BW represented a simple reversal of FW and, hence muscle force distribution is the same. The study involved one male healthy student of physical education (22 years, h = 185 cm, m = 80 kg). Measurements of spatial-temporal gait parameters were conducted using eight Vicon system cameras, and Kistler plates. Noraxon EMG was used to obtain muscles activity. OpenSim software was used to compute muscle force distribution during both types of gait. During FW and BW there is small difference for force curves produced by m. gluteus maximus (RMS = 0.04), m. biceps femoris short head (RMS = 0.19) and m. tibialis anterior (RMS = 0.16). Good validation by EMG signal was obtained for m. rectus femoris, m. biceps femoris short head, m. tibialis posterior during FW and BW. For m. iliacus, only during BW good validation was achived. PMID- 24215108 TI - Gold network structures in rhombohedral and monoclinic Sr2Au6(Au,T)3 (T = Zn, Ga). A transition via relaxation. AB - Quantitative syntheses, structure determinations and interpretations, and band calculations are reported for the nonstoichiometric rhombohedral (R3c) and monoclinic (C2/c) Sr2Au6(Au(3-x)T(x)) (T = Zn, Ga) compounds. Several different compositions of the two Sr phases were similarly refined from single crystal X ray diffraction data as R3c: a ~ 8.43 A, c ~ 21.85 A, Z = 6 and C2/c: a ~ 14.70 A, b ~ 8.47 A, c ~ 8.70 A, beta ~ 123.2 degrees , Z = 4. The R3c Zn phase is stable in the composition region x ~ 2.5-2.9 whereas its C2/c neighbor is the major product at x ~ 2.2-2.3. Gallium versions of both were also identified. Both R3c and C2/c structural types contain hexagonal-diamond-like gold superlattices stuffed with strings of interstitial Sr and disordered triangular (Au,T)3 units. The latter space group is a maximal, nonisomorphic subgroup of the former, and the decrease in interstitial radius from Ba to Sr (~0.08 A experimentally) evidently drives the symmetry reduction, relaxation, and small distortions, principally around the Sr sites. Au-Au bonding among the Au hexagons in the host lattices and with gold components in the triangular interstitials is dominant and reflected in their tight packing and short interatomic separations. PMID- 24215109 TI - Porous orbital implant exposure: the influence of surgical technique. AB - OBJECTIVES: To examine orbital implant exposure rates following enucleation and evisceration. METHODS: A retrospective chart review of all patients who underwent an evisceration or enucleation in a single centre over a 5-year period was performed. The indication for surgery, the type and size of orbital implant used, details of the surgical technique adopted and the postoperative complications observed, in particular orbital implant exposure, were recorded. RESULTS: Over a 5-year period 24 patients had enucleation and 14 had evisceration; 22 of these procedures were performed by an ophthalmic surgeon with a special interest in orbit and oculoplastics while the remaining 16 procedures were performed by 5 ophthalmic surgeons with other sub-specialty interests. Orbital implant exposure occurred in 8 cases. One case had been performed by the first of these surgeons described. Implant exposure occurred in 4% of cases performed by this surgeon. The remaining 7 cases had been performed by the group of surgeons with sub specialty interests outside of orbit and oculoplastics. Implant exposure occurred in 48% of cases performed by this group. CONCLUSIONS: Orbital implant exposure remains a significant cause of morbidity in patients undergoing enucleation and evisceration. Rates of orbital implant exposure were significantly lower when surgery was performed by an orbital surgeon. Differences in surgical technique are the most likely explanation. PMID- 24215110 TI - Development of nanoparticles-in-microparticles system for improved local retention after intra-articular injection. AB - To increase the intra-articular (IA) retention time of osteoarthritis drugs in the synovial cavity and slow down the burst release of microspheres (MPs), we prepared a novel drug delivery system named nanoparticles-in-microspheres (NiMs). The system was constructed by dispersing the brucine-loaded nanoparticle, which was prepared by an emulsification method in the MPs. The NiMs were characterized by scanning electron microscope, Fourier transform infrared spectra and differential scanning calorimetry. After investigating the biocompatibility with synovium of NiMs in rats, the pharmacokinetics was studied and FX-imaging was used to visualize the transmission of nanoparticles after IA administration in rats. From the results, we know that the NiMs were spherical, there was no chemical bond between the drug and the polymer, and the drug was dispersed in the polymer in an amorphous form. Compared with MPs (41%), the burst release of NiMs could be slowed down to 9%. After that, the drug was released from NiMs by diffusion. The results of FX imaging in rats showed that the NiMs could stay in the articular cavity for over 11 d. The studies of pharmacokinetics revealed that the NiMs could slow down the burst release and improve retention in vivo. This study demonstrates the feasibility of using NiMs to slow down the burst release and increase the retention of therapeutic agents in articular joints. PMID- 24215111 TI - Molecular mechanism of stabilization of thin films for improved water evaporation protection. AB - All-atom molecular dynamics simulations and experimental characterization have been used to examine the structure and dynamics of novel evaporation-suppressing films where the addition of a water-soluble polymer to an ethylene glycol monooctadecyl ether monolayer leads to improved water evaporation resistance. Simulations and Langmuir trough experiments demonstrate the surface activity of poly(vinyl pyrrolidone) (PVP). Subsequent MD simulations performed on the thin films supported by the PVP sublayer show that, at low surface pressures, the polymer tends to concentrate at the film/water interface. The simulated atomic concentration profiles, hydrogen bonding patterns, and mobility analyses of the water-polymer-monolayer interfaces reveal that the presence of PVP increases the atomic density near the monolayer film, improves the film stability, and reduces the mobility of interfacial waters. These observations explain the molecular basis of the improved efficacy of these monolayer/polymer systems for evaporation protection of water and can be used to guide future development of organic thin films for other applications. PMID- 24215112 TI - A glimpse into the world of battered ultra-Orthodox Jewish women in Israel: a follow-up study on women who resided in a shelter. AB - Using a mixed-methods approach to content analysis, we interviewed 88 ultra Orthodox Jewish women who had endured spousal abuse and chose to find refuge in the only shelter in Israel specifically designated for religious women. All had experienced some type of spousal abuse for several years. The majority summarized the period they spent in the shelter in positive terms and reported that they had developed personal strength and that their social and family relationships had improved. About half of them described the postshelter period in positive terms, while the rest described it in both positive and negative terms or in negative terms only. Negative themes were mostly related to the women's economic situation and to emotional and behavioral problems of their children. Further research is required to expand existing knowledge regarding this population. PMID- 24215113 TI - Finding the active genes in deep RNA-seq gene expression studies. AB - BACKGROUND: Early application of second-generation sequencing technologies to transcript quantitation (RNA-seq) has hinted at a vast mammalian transcriptome, including transcripts from nearly all known genes, which might be fully measured only by ultradeep sequencing. Subsequent studies suggested that low-abundance transcripts might be the result of technical or biological noise rather than active transcripts; moreover, most RNA-seq experiments did not provide enough read depth to generate high-confidence estimates of gene expression for low abundance transcripts. As a result, the community adopted several heuristics for RNA-seq analysis, most notably an arbitrary expression threshold of 0.3 - 1 FPKM for downstream analysis. However, advances in RNA-seq library preparation, sequencing technology, and informatic analysis have addressed many of the systemic sources of uncertainty and undermined the assumptions that drove the adoption of these heuristics. We provide an updated view of the accuracy and efficiency of RNA-seq experiments, using genomic data from large-scale studies like the ENCODE project to provide orthogonal information against which to validate our conclusions. RESULTS: We show that a human cell's transcriptome can be divided into active genes carrying out the work of the cell and other genes that are likely the by-products of biological or experimental noise. We use ENCODE data on chromatin state to show that ultralow-expression genes are predominantly associated with repressed chromatin; we provide a novel normalization metric, zFPKM, that identifies the threshold between active and background gene expression; and we show that this threshold is robust to experimental and analytical variations. CONCLUSIONS: The zFPKM normalization method accurately separates the biologically relevant genes in a cell, which are associated with active promoters, from the ultralow-expression noisy genes that have repressed promoters. A read depth of twenty to thirty million mapped reads allows high-confidence quantitation of genes expressed at this threshold, providing important guidance for the design of RNA-seq studies of gene expression. Moreover, we offer an example for using extensive ENCODE chromatin state information to validate RNA-seq analysis pipelines. PMID- 24215114 TI - Chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract against chromium-induced testicular toxicity in rats. AB - This study was conducted to determine the mechanism underlying the chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract (MOLEE) against chromium-induced impairments of rat testes using biochemical methods. Twenty male Wistar rats were divided into four groups of five animals each. Group I (control), group II injected potassium dichromate (8 mg kg(-1) ) i.p., group III gastrogavaged MOLEE (500 mg kg(-1) ) p.o. and group IV received (potassium dichromate plus MOLEE) by the same doses for 60 days. After the blood samples were collected, the animals were sacrificed to determine the testicular antioxidant status and sperm parameters. The chromium-treated group exhibited a significant decrease in testicular antioxidant enzymatic activities, local immunity and sperm parameters as well as an increase in inflammatory markers when compared with the control and MOLEE-treated group. However, concurrent administration of chromium and MOLEE significantly ameliorated the chromium effects on the sperm parameters, local immunity, inflammatory markers and antioxidant enzymatic activities compared with rats exposed to chromium alone. This study concludes that chronic exposure to chromium produces clear testicular toxicity, which can either be prevented or at least decreased by concomitant administration of MOLEE. Interestingly, the metal ion chelation could attribute partly the antioxidant activities of MOLEE. PMID- 24215115 TI - Asymmetric NHC-catalyzed redox alpha-amination of alpha-aroyloxyaldehydes. AB - Asymmetric alpha-amination through an N-heterocyclic carbene (NHC)-catalyzed redox reaction of alpha-aroyloxyaldehydes with N-aryl-N-aroyldiazenes to form alpha-hydrazino esters with high enantioselectivity (up to 99% ee) is reported. The hydrazide products are readily converted into enantioenriched N-aryl amino esters through samarium(II) iodide mediated N-N bond cleavage. PMID- 24215116 TI - Infrared LED irradiation photobiomodulation of oxidative stress in human dental pulp cells. AB - AIM: To investigate the effect of infrared light-emitting diode (LED) irradiation on the oxidative stress induced in human dental pulp cells (HDPCs) by lipopolysaccharide (LPS). METHODOLOGY: Human dental pulp cells (HDPCs) were harvested from sound primary teeth that were near exfoliation. Cells were seeded (10(5) cells cm(-2) ) using alpha-MEM supplemented with 10% FBS and after 24 h, were placed in contact with LPS (10 MUg mL(-1) of culture medium). Immediately afterwards, HDPCs were subjected to a single irradiation with an infrared LED (855 nm) delivering different doses of energy (0, 2, 4, 8, 15 or 30 J cm(-2) ). For each dose, there was a control group without LPS application. Twenty-four hours after irradiation, groups were tested for nitric oxide (NO) quantification, cell viability (MTT assay) and qualitative assessment of reactive oxygen species (ROS). Data were submitted to Kruskal-Wallis and Mann-Whitney tests (alpha = 0.05). RESULTS: Lipopolysaccharide (LPS)-induced stress resulted in significant increase in NO production by HDPC without causing damage to cell respiratory metabolism. Irrespective of energy dose delivered, NO production was significantly reduced when LPS-stressed cells were irradiated with infrared LED (2 J cm(-2) , P = 0.003; 95% CI = 5.84-27.71; 4 J cm(-2) , P = 0.001; 95% CI = 7.52-26.39; 8 J cm(-2) , P = 0.0195; 95% CI = -2.86-16.01; 15 J cm(-2) , P = 0.0001; 95% CI = 12.10-30.96; 30 J cm(-2) , P = 0.007; 95% CI = 5.84-24.71). The highest decrease in NO production was observed when 15 J cm(-2) was delivered to cells. Infrared LED irradiation resulted in a decrease in ROS production, whilst HDPC metabolism was not significantly affected. CONCLUSION: Biomodulation of oxidative stress of HPDC can be achieved by irradiation with a single dose of infrared LED. Within the range investigated, 15 J cm(-2) resulted in the least production of NO. PMID- 24215117 TI - Obstetrician-initiated counseling and testing for HIV infection: a cross sectional study. AB - OBJECTIVE: To assess the practice of provider-initiated counseling and testing (PICT) for HIV infection by Nigerian Obstetricians and estimate missed opportunities at the gynecological and family planning clinics. METHODS: Online cross-sectional survey of members of the Society of Gynaecology and Obstetrics of Nigeria (SOGON) over a 4-week period using SurveyMonkey(r). Frequencies were used to present responses of participants. RESULTS: There were 201 (29%) respondents. Participants' mean age was 46 +/- 7.2 (SD) years and majority (93.3%) held consultant positions. Most respondents (92.2%) cared for HIV-infected pregnant women with dedicated HIV counselors (77.4%), and in dedicated counseling rooms (71%). Majority (75.7%) had been trained on HIV management in pregnancy and 95.3% routinely counseled and tested women attending the booking antenatal clinic. Fourteen per cent (14%) and 16% of respondents conducted routine counseling and testing for women attending the gynecological and family planning clinics, respectively, for the first time. For every 100 women tested at the antenatal clinic, 317 women were missed at each of the two clinics. CONCLUSIONS: PICT of HIV infection in Nigeria has focused on pregnancy. To eliminate new HIV infections in children, PICT should be routine at the gynecological and family planning clinics. PMID- 24215118 TI - Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarrays. AB - OBJECTIVE: To evaluate the expression and prognostic value of epithelial cell adhesion/activating molecule (EpCAM) in a large set of renal cell carcinomas (RCCs) using a tissue microarray (TMA) approach. MATERIAL AND METHODS: We studied the immunohistochemical expression and overexpression of EpCAM on TMAs containing formalin-fixed, paraffin-embedded samples of 948 patients with documented renal tumours. EpCAM expression was defined as the presence of a specific membranous staining in >5% of the tumour cells. EpCAM overexpression was specified by calculating a total staining score (score range 0-12) as the product of a proportion score and an intensity score, and defined as a score >4. RESULTS: Of 948 cases, 927 (97.8%) were evaluable morphologically (haematoxylin and eosin stain). EpCAM expression was found in 233/642 (36.3%), 126/155 (81.3%), 54/68 (78.3%), 17/45 (37.8%), 13/30 (43.3%) of clear-cell RCC, papillary RCC (pRCC), chromophobe RCC (cpRCC), oncocytomas and other unclassified tumour types, respectively. Log-rank tests showed a significantly longer overall survival (OS [P = 0.047]) and a trend of EpCAM expression to be associated with a longer progression-free survival (PFS) in all RCC entities (P = 0.065). EpCAM overexpression was significantly correlated with a better PFS in all RCC subtypes, cpRCC and pRCC (P = 0.011, 0.043 and 0.025, respectively). In multivariate analysis EpCAM overexpression was an independent marker for longer PFS in all RCC entities as well as in high grade RCC (P = 0.009 and P = 0.010, respectively). CONCLUSIONS: The histological subtypes associated with a high rate of EpCAM expression were cpRCC and pRCC. This retrospective analysis demonstrated a trend towards longer OS and PFS for all major RCC subtypes. EpCAM expression had significant prognostic value in patients with cpRCC and pRCC. Furthermore, EpCAM overexpression in high grade RCC may be a helpful marker for prognostication. PMID- 24215119 TI - Precision of jaw-closing movements for different jaw gaps. AB - Jaw-closing movements are basic components of physiological motor actions precisely achieving intercuspation without significant interference. The main purpose of this study was to test the hypothesis that, despite an imperfect intercuspal position, the precision of jaw-closing movements fluctuates within the range of physiological closing movements indispensable for meeting intercuspation without significant interference. For 35 healthy subjects, condylar and incisal point positions for fast and slow jaw-closing, interrupted at different jaw gaps by the use of frontal occlusal plateaus, were compared with uninterrupted physiological jaw closing, with identical jaw gaps, using a telemetric system for measuring jaw position. Examiner-guided centric relation served as a clinically relevant reference position. For jaw gaps <=4 mm, no significant horizontal or vertical displacement differences were observed for the incisal or condylar points among physiological, fast, and slow jaw-closing. However, the jaw positions under these three closing conditions differed significantly from guided centric relation for nearly all experimental jaw gaps. The findings provide evidence of stringent neuromuscular control of jaw-closing movements in the vicinity of intercuspation. These results might be of clinical relevance to occlusal intervention with different objectives. PMID- 24215121 TI - Shape optimisation of a ventricular assist device using a VADFEM computer program. AB - The Polish ventricular assist device, POLVAD_EXT, is made of a polymer designed to be covered with a nanocoating of titanium nitride to improve haemocompatibility. A loss of cohesion can occur between the coating and the substrate. An analysis of stress and strain states in a multi-scale model of the blood chamber was performed in the finite element computer program, VADFEM. The multiscale model is composed of a macro model of the blood chamber and a micro model of the titanium nitride (TiN) deposited on the polymer. The finite element method and the goal function, based on the triaxiality factor, are used to solve the problems formulated. The theories of non-linear elasticity and elasto plasticity are applied. The goal of the paper is to optimise the construction of the POLVAD_EXT with respect to shape parameters. PMID- 24215120 TI - Evaluating differential developmental trajectories to adolescent-onset mood and psychotic disorders. AB - BACKGROUND: It is an open question as to whether differential developmental trajectories, potentially representing underlying pathophysiological processes, can form the basis of a more useful typology in young persons who present for mental health care. METHODS: A cohort of 605 young people was recruited from youth mental health services that target the early phases of anxiety, mood or psychotic disorders. Participants were assigned to one of three clinical sub types (anxious-depression; mania-fatigue; developmental-psychotic) according to putative developmental trajectories. RESULTS: The distribution of subtypes was: 51% anxiety-depression, 25% mania-fatigue and 24% developmental-psychotic, with key differences in demographic, clinical, family history and neuropsychological characteristics. When analyses were limited to 286 cases with 'attenuated' or sub threshold syndromes, the pattern of differences was similar. Multinomial logistic regression demonstrated that compared to the developmental-psychotic subtype, both the mania-fatigue and anxiety-depression subtypes were younger and more depressed at presentation, but less functionally impaired. Other discriminating variables between the developmental-psychotic and mania-fatigue sub-types were that the latter were significantly more likely to have a family history of bipolar disorder but have less likelihood of impaired verbal learning; whilst the anxious-depression group were more anxious, more likely to have a family history of depression, and had a higher premorbid IQ level. CONCLUSIONS: This cross sectional evaluation provides preliminary support for differing developmental trajectories in young persons presenting for mental health care. Prospective follow-up is needed to examine the predictive validity of this approach and its relationships to underlying pathophysiological mechanisms. PMID- 24215123 TI - Making concrete construals mindful: a novel approach for developing mindfulness and self-compassion to assist weight loss. AB - Research on the usefulness of mindfulness and self-compassion for dieting has focused on meditative practices. However, meditation can be difficult to maintain, especially while dieting. Thus, the present research attempted to induce mindfulness and self-compassion by using food diaries that required the participant to either focus on concrete (i.e. how they are eating) construals or abstract (i.e. why they are eating) construals. The concrete construals were expected to increase mindfulness and self-compassion, as well as decrease avoidance and negative thoughts (which would further aid the development of mindfulness and self-compassion). Study 1 found that mindfulness and self compassion mediated the inverse relationship of avoidance and negative thoughts with weight loss. Study 2 showed that concrete construal diaries increased mindfulness and self-compassion, decreased avoidance and negative thoughts, and supported weight loss significantly more than the abstract construal diaries. Study 3, then, compared the concrete construal diaries with a mindful self compassionate meditation programme. There was no difference in weight loss at the end of the intervention, but at a three-month follow-up, the diaries performed better at weight maintenance. Thus, the concrete construal diaries may promote mindfulness and self-compassion and potentially promote long-term weight loss. PMID- 24215124 TI - Arginine-stabilized mPEG-PDLLA (50/50) polymeric micelles of docetaxel by electrostatic mechanism for tumor-targeted delivery. AB - Arginine-stabilized, docetaxel-loaded polymeric micelles (AR-DTX-PM) were prepared to enhance the physical stability of micelles and control the degradation of docetaxel (DTX). Amphiphilic diblock copolymers, methoxy (Polyethylene Glycol)-block-Poly (D, L-lactide) (mPEG-PDLLA) were synthesized and used for the formulation of lyophilized DTX-PM powders. The micelles were found to have diameters of 20-30 nm with narrow polydispersity, and the entrapment efficiency was 90-100%. The accumulative release of AR-DTX-PM was higher than that of glucose-dispersed DTX-PM (Glu-DTX-PM). The results of both physical and chemical stability studies showed that the concentration of arginine required for optimum stability was 2.0 mg/ml. Preliminary investigation of the mechanisms of stabilization by arginine suggested that it is due to the electrostatic interaction as well as hydrogen bonds between DTX and arginine. The acute toxicity studies demonstrated that AR-DTX-PM was better tolerated in beagle dogs than DTX injection. However, the pharmacokinetic studies revealed no significant difference in Cmax and AUC of AR-DTX-PM compared to DTX injection. When AR-DTX-PM was administrated at a dose of 30 mg/kg, the antitumor effect was stronger than that of commercial DTX injection at 10 mg/kg, and the increase of administration dose did not cause higher toxicity. The in vivo imaging test showed that the residence time of AR-DTX-PM at tumor sites was longer than its commercial formulation. In a word, it is expected that AR-DTX-PM can reduce systemic toxicity while retaining antitumor efficacy in cancer patients. PMID- 24215126 TI - Highly enantioselective synthesis of tetrahydrocarbolines via iridium-catalyzed intramolecular Friedel-Crafts type allylic alkylation reactions. AB - A highly enantioselective synthesis of substituted tetrahydrocarbolines via Ir catalyzed Friedel-Crafts type intramolecular asymmetric allylic alkylation of 2 indolyl allyl carbonates has been developed. This strategy features excellent chemoselectivity and enantioselectivity, mild reaction conditions, and an easily accessed chiral ligand. PMID- 24215125 TI - GSK3 alpha and beta are new functionally relevant targets of tivantinib in lung cancer cells. AB - Tivantinib has been described as a potent and highly selective inhibitor of the receptor tyrosine kinase c-MET and is currently in advanced clinical development for several cancers including non-small cell lung cancer (NSCLC). However, recent studies suggest that tivantinib's anticancer properties are unrelated to c-MET inhibition. Consistently, in determining tivantinib's activity profile in a broad panel of NSCLC cell lines, we found that, in contrast to several more potent c MET inhibitors, tivantinib reduces cell viability across most of these cell lines. Applying an unbiased, mass-spectrometry-based, chemical proteomics approach, we identified glycogen synthase kinase 3 (GSK3) alpha and beta as novel tivantinib targets. Subsequent validation showed that tivantinib displayed higher potency for GSK3alpha than for GSK3beta and that pharmacological inhibition or simultaneous siRNA-mediated loss of GSK3alpha and GSK3beta caused apoptosis. In summary, GSK3alpha and GSK3beta are new kinase targets of tivantinib that play an important role in its cellular mechanism-of-action in NSCLC. PMID- 24215127 TI - Intravitreal injection of ranibizumab for treatment of age-related macular degeneration: effects on serum VEGF concentration. AB - AIMS: To evaluate potential adverse ranibizumab-related systemic events through analysis of variations in serum levels of vascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (AMD) patients before and after a single intravitreal injection of ranibizumab. METHODS: Thirty-nine patients with neovascular AMD and 39 healthy control subjects were enrolled in the study. Patients received a single intravitreal injection of ranibizumab (0.5 mg) in one eye. Venous blood was collected and placed in coagulation-promoting tubes 1 day before and on post-injection days 1, 3, 7 and 30. Serum concentrations of VEGF were measured by ELISA at each time point. RESULTS: VEGF concentrations were 323.64 pg/ml in AMD patients and 392.94 pg/ml in control subjects before injection (p > 0.05). VEGF significantly decreased to 304.65 pg/ml 1 day later (p < 0.05) in AMD patients, then increased to 310.77 (p > 0.05), 317.89 (p > 0.05) and 311.79 pg/ml (p > 0.05) on post-injection days 3, 7 and 30, respectively. CONCLUSION: No significant changes in serum levels of VEGF were found from 3 to 30 days following a single intravitreal ranibizumab injection. Although certain influences existed 24-h post-injection, effect(s) of a single intravitreal ranibizumab injection on the homeostasis of the cardiovascular system during such a brief period is unknown. PMID- 24215128 TI - Mechanical behaviour of the implant used in human hernia repair under physiological loads. AB - In laparoscopic operations of abdominal hernias some recurrences still take place, even when applying a surgical mesh. This is usually caused by a failure of the connection between the tissue and the implant. The study deals with the influence of an implant's orientation on forces in joints, which connect the mesh to human tissues. In the paper, the implant is modelled as a membrane structure within framework of the Finite Element Method. Two models are analysed: in the first one interaction between the mesh and a fascia is taken into account, in the second this interaction is not considered. Computations are conducted for two different material types of the implants: one with isotropic properties and second one with orthotropic properties. The models are validated by comparing dynamic numerical analysis with experimental outcomes, where load was simulating intraabdominal pressure during postoperative cough. Due to displacements of joints during activities like bending sideways or torsion of an abdomen, influence of kinematic extortions on forces in the joints is analysed. The outcome shows that position of the orthotropic implants is crucial and may strongly change the level of forces in the joints. PMID- 24215129 TI - Radical versus partial nephrectomy for a small renal mass: does saving nephrons save lives? PMID- 24215131 TI - Beckwith-Wiedemann syndrome with overlapping Perlman syndrome manifestation. AB - Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome known as exomphalos macroglossia - gigantism syndrome. Prognosis is good, prenatal diagnosis is important for pregnancy management but might be difficult due to clinical overlap with other syndromes. Perlman syndrome is an overgrowth syndrome with high perinatal mortality, most frequent antenatal findings include polyhydramnios, macrosomia, visceromegaly, nephromegaly and foetal ascites. Authors present a case of prenatally diagnosed BWS with severe ascites as first antenatal finding and lethal course, signs more typical of Perlman syndrome. This combination of clinical signs has not been published yet and may contribute to specification of possible prenatal manifestation of BWS. PMID- 24215130 TI - Genomic and physiological responses to strong selective pressure during late organogenesis: few gene expression changes found despite striking morphological differences. AB - BACKGROUND: Adaptations to a new environment, such as a polluted one, often involve large modifications of the existing phenotypes. Changes in gene expression and regulation during critical developmental stages may explain these phenotypic changes. Embryos from a population of the teleost fish, Fundulus heteroclitus, inhabiting a clean estuary do not survive when exposed to sediment extract from a site highly contaminated with polycyclic aromatic hydrocarbons (PAHs) while embryos derived from a population inhabiting a PAH polluted estuary are remarkably resistant to the polluted sediment extract. We exposed embryos from these two populations to surrogate model PAHs and analyzed changes in gene expression, morphology, and cardiac physiology in order to better understand sensitivity and adaptive resistance mechanisms mediating PAH exposure during development. RESULTS: The synergistic effects of two model PAHs, an aryl hydrocarbon receptor (AHR) agonist (beta-naphthoflavone) and a cytochrome P4501A (CYP1A) inhibitor (alpha-naphthoflavone), caused significant developmental delays, impaired cardiac function, severe morphological alterations and failure to hatch, leading to the deaths of reference embryos; resistant embryos were mostly unaffected. Unexpectedly, patterns of gene expression among normal and moderately deformed embryos were similar, and only severely deformed embryos showed a contrasting pattern of gene expression. Given the drastic morphological differences between reference and resistant embryos, a surprisingly low percentage of genes, 2.24% of 6,754 analyzed, show statistically significant differences in transcript levels during late organogenesis between the two embryo populations. CONCLUSIONS: Our study demonstrates important contrasts in responses between reference and resistant natural embryo populations to synergistic effects of surrogate model PAHs that may be important in adaptive mechanisms mediating PAH effects during fish embryo development. These results suggest that statistically significant changes in gene expression of relatively few genes contribute to the phenotypic changes and large morphological differences exhibited by reference and resistant populations upon exposure to PAH pollutants. By correlating cardiac physiology and morphology with changes in gene expression patterns of reference and resistant embryos, we provide additional evidence for acquired resistance among embryos whose parents live at heavily contaminated sites. PMID- 24215133 TI - Optically controlled thermophoretic trapping of single nano-objects. AB - Brownian motion is driven by thermal fluctuations and becoming more efficient for decreasing size and elevated temperatures. Here, we show that despite the increased fluctuations local temperature fields can be used to localize and control single nano-objects in solution. By creating strong local temperature gradients in a liquid using optically heated gold nanostructures, we are able to trap single colloidal particles. The trapping is thermophoretic in nature, and thus no restoring body force is involved. The simplicity of the setup allows for an easy integration and scalability to large arrays of traps. PMID- 24215132 TI - Peptide amphiphile containing arginine and fatty acyl chains as molecular transporters. AB - Peptide amphiphiles (PAs) are promising tools for the intracellular delivery of numerous drugs. PAs are known to be biodegradable systems. Here, four PA derivatives containing arginine and lysine conjugated with fatty acyl groups with different chain lengths, namely, PA1: R-K(C14)-R, PA2: R-K(C16)-R, PA3: K(C14)-R K(C14), and PA4: K(C16)-R-K(C16), where C16 = palmitic acid and C14 = myristic acid, were synthesized through Fmoc chemistry. Flow cytometry studies showed that, among all synthesized PAs, only K(C16)-R-K(C16), PA4 was able to enhance the cellular uptake of a fluorescence-labeled anti-HIV drug 2',3'-dideoxy-3' thiacythidine (F'-3TC, F' = fluorescein) and a biologically important phosphopeptide (F'-PEpYLGLD) in human leukemia cells (CCRF-CEM) after 2 h incubation. For example, the cellular uptake of F'-3TC and F'-PEpYLGLD was enhanced approximately 7.1- and 12.6-fold in the presence of the PA4 compared to those of the drugs alone. Confocal microscopy of F'-3TC and F'-PEpYLGLD loaded PA4 in live cells showed significantly higher intracellular localization than the drug alone in human ovarian cells (SK-OV-3) after 2 h incubation. The high performance liquid chromatography (HPLC) results showed that loading of Dox by the peptide amphiphile was 56% after 24 h. The loaded Dox was released (34%) within 48 h intracellularly. The circular dichrosim (CD) results exhibited that the secondary structure of the peptide was changed upon interactions with Dox. Mechanistic studies revealed that endocytosis is the major pathway of the internalization. These studies suggest that PAs containing the appropriate sequence of amino acids, chain length, charge, and hydrophobicity can be used as cellular delivery tools for transporting drugs and biomolecules. PMID- 24215134 TI - Sport and nonsport etiologies of mild traumatic brain injury: similarities and differences. AB - Mild traumatic brain injury (mTBI) has recently gained appreciation as a significant public health problem, which has highlighted just how little is known about its proximal and long-term effects. A major challenge in the study of mTBI is the heterogeneity of the condition. Research on mTBI has historically separated sport and nonsport etiologies, and the extent to which research from one of these samples translates to the other is unclear. This review examines the literature on mTBI, with a focus on comparing sport and nonsport etiologies with regard to the latest research on biomechanics, pathophysiology, neurocognitive effects, and neuroimaging. Issues of particular relevance to sports injuries, such as exercise, repetitive injuries, subconcussive blows, and chronic injury effects, are also reviewed. PMID- 24215136 TI - Free-floating pyogenic granuloma of the lacrimal sac. AB - The authors report a 13-month-old girl with chronic dacryocystitis, and history of three times probing and once inferior turbinate infracture. She underwent dacryocystorhinostomy due to failure of previous procedures. During surgery a free floating reddish mass was extracted from the lacrimal sac. Histopathologic examination revealed the mass to be a pyogenic granuloma. PMID- 24215135 TI - Understanding factors that influence protective glove use among automotive spray painters. AB - Dermal contact with isocyanate-based coatings may lead to systemic respiratory sensitization. The most common isocyanates found in sprayed automotive coatings are monomeric and oligomeric 1,6-hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI). Most spray painters use thin (4-5 mil) latex gloves that are not effective at preventing dermal exposures when spraying isocyanate paints. Personal interviews with collision repair industry personnel and focus groups with spray painters were held to characterize risk awareness, to examine perceptions and challenges concerning protective glove use and selection, and to generate ideas for protective glove use interventions. The most popular gloves among spray painters were thin (4-5 mil) and thick (14 mil) latex. We found that medium to thick (6-8 mil) nitrile were not always perceived as comfortable and were expected to be more expensive than thin (4-5 mil) latex gloves. Of concern is the user's difficulty in distinguishing between nitrile and latex gloves; latex gloves are now sold in different colors including blue, which has traditionally been associated with nitrile gloves. Even though spray painters were familiar with the health hazards related to working with isocyanate paints, most were not always aware that dermal exposure to isocyanates could contribute to the development of occupational asthma. There is a need for more research to identify dermal materials that are protective against sprayed automotive coatings. Automotive spray painters and their employers need to be educated in the selection and use of protective gloves, specifically on attributes such as glove material, color, and thickness. PMID- 24215137 TI - Wells-Dawson cages as molecular refrigerants. AB - Five clusters with the general formula [Ni6Gd6(MU3-OH)2(MU2 OAc)2(O3PR)6(O2C(t)Bu)16], where R = methyl (1), phenyl (2), n-hexyl (3), benzyl (4), n-octyl (5), have been prepared. All of the clusters have a {Ni6Gd6P6} core that can be related to the Wells-Dawson ion. We have also prepared analogues where the gadolinium is replaced with diamagnetic yttrium: [Ni6Y6(MU3-OH)2(MU2 OAc)2(O3PR)6(O2C(t)Bu)16] (R = methyl (6), n-hexyl (7), benzyl (8), n-octyl (9)), allowing the magnetic exchange within the {Ni3} units to be analyzed by modeling as the sum of two noninteracting isosceles triangles. The variation in the magnetic entropy changes for magnetization (-DeltaSM) among compounds 1-5 could be attributed not only to the molecular weight of the compounds but also to intramolecular magnetic interactions. PMID- 24215138 TI - Perception of masculinity amongst young Malaysian men: a qualitative study of university students. AB - BACKGROUND: Perception of Masculinity plays an important role in men's lifestyles and health behaviors. Although, the importance of masculinity has been widely discussed in men's health literature, very little is known about the meanings of masculinity in the Malaysian setting. This research aimed to explore the meanings of masculinity among Malaysian university men. METHODS: This qualitative study utilized in-depth interviews with 34 young Malaysian university men, aged 20-30 years from three main ethnic groups in Malaysia (Malay, Chinese and Indian). Thematic analysis approach was used to extract data. NVIVO v8 qualitative software was used for data management. RESULTS: From the data collected several concepts emerged that reflected the meanings of masculinity from the participants' view points. These meanings were associated with a combination of traditional and non-traditional norms that generally benefit men who behave according to culturally dominant role expectations. These included: "Having a good body shape", "being respected", "having success with women", "being a family man", and "having financial independence". Socio-cultural factors, such as family environment, religion, public media and popular life style patterns helped to shape and reinforce the meanings of masculinities among university men. CONCLUSIONS: This study revealed that the university context provided a particular culture for construction and reinforcement of the meanings of masculinities, which should be considered by the educators to help in development of healthy masculinities. PMID- 24215139 TI - Recent insights into NF-kappaB signalling pathways and the link between inflammation and prostate cancer. AB - Inflammation is involved in regulation of cellular events in prostate carcinogenesis through control of the tumour micro-environment. A variety of bone marrow-derived cells, including CD4+ lymphocytes, macrophages and myeloid-derived suppressor cells, are integral components of the tumour micro-environment. On activation by inflammatory cytokines, NF-kappaB complexes are capable of promoting tumour cell survival through anti-apoptotic signalling in prostate cancer (PCa). Positive feedback loops are able to maintain NF-kappaB activation. NF-kappaB activation is also associated with the metastatic phenotype and PCa progression to castration-resistant prostate cancer (CRPC). A novel role for inhibitor of NF-kappaB kinase (IKK)-alpha in NF-kappaB-independent PCa progression to metastasis and CRPC has recently been uncovered, providing a new mechanistic link between inflammation and PCa. Expansion of PCa progenitors by IKK-alpha may be involved in this process. In this review, we offer the latest evidence regarding the role of the NF-kappaB pathway in PCa and discuss therapeutic attempts to target the NF-kappaB pathways. We point out the need to further dissect inflammatory pathways in PCa in order to develop appropriate preventive measures and design novel therapeutic strategies. PMID- 24215140 TI - Relationship between fear of falling and mobility varies with visual function among older adults. AB - AIM: The present study examined the association between vision, fear of falling and fear-related activity restriction, and assessed the effect of vision on the relationship between fear of falling and mobility, using data from a nationally representative sample of community-dwelling adults aged >= 50 years. METHODS: Participants (n=5003) completed an interview and health assessment (including Timed Up-and-Go, vision and cognitive tests). Visual acuity and contrast sensitivity were assessed using an Early Treatment Diabetic Retinopathy Study logMAR chart and Functional Vision Analyzer, respectively. Participants self reported their vision as excellent, very good, good, fair or poor. They were assigned to no fear of falling, fear without activity restriction and fear with activity restriction groups. Logistic regression models examined the relationship between vision, fear of falling and activity restriction. Linear regression models were used to examine the main and interaction effects of fear of falling, self-reported vision, visual acuity, and contrast sensitivity on mobility after adjusting for confounders. RESULTS: Poorer self-reported vision was independently associated with fear of falling and fear-related activity restriction (P<0.05), but visual acuity and contrast sensitivity were not. Participants with the lowest visual acuity and contrast sensitivity levels, combined with fear-related activity restriction, had slower Timed Up-and-Go than those in the highest visual performance quartiles (P<0.05). CONCLUSIONS: Participants' perceptions of visual function were related to fear of falling and activity restriction, but this was not explained by other visual factors measured here. However, poorer visual acuity and contrast sensitivity did moderate the relationship between fear related activity restriction and mobility, highlighting the importance of a comprehensive vision assessment especially in individuals with fear of falling. PMID- 24215141 TI - Microparticles of rifampicin: comparison of pulmonary route with oral route for drug uptake by alveolar macrophages, phagocytosis activity and toxicity study in albino rats. AB - CONTEXT: Tuberculosis (TB) is a chronic infectious disease with increasing incidence of drug resistance. Oral treatment for TB and multidrug resistance (MDR)-TB can have serious side effects. The causative agent of TB, Mycobacterium tuberculosis, resides in alveolar macrophages (AM). Pulmonary administration of anti-TB drugs can help in delivery of high concentration to AM. The ability of AM to phagocytose can also be utilized to generate mycobactericidal nitric oxide (NO) to improve efficacy of anti-TB drugs. OBJECTIVE: To compare the uptake of rifampicin (RIF) by AM post oral and pulmonary administration of RIF microparticles (RM) and to compare hepatotoxicity and phagocytosis activity. MATERIALS AND METHODS: RM were produced by spray drying process. RM were administered to rats through oral as well as intratracheal route. The uptake of RIF by AM and liver was measured. NO was measured in bronchoalveolar lavage (BAL) fluid. SGOT and SGPT levels were measured in serum. RESULTS: Significantly higher (p < 0.05) concentration of RIF was found in AM post intratracheal administration. NO production was also significantly higher but less than toxic level. SGOT and SGPT levels as well as uptake of RIF by liver were indicative of no hepatotoxicity post intratracheal administration. DISCUSSION: Phagocytosis of RM post intratracheal administration leads to significantly higher drug level in AM as well as production of significantly higher levels of NO. CONCLUSION: The administration of RM as dry powder inhalation (DPI) formulation may reduce treatment time of TB and chances of drug resistance TB. PMID- 24215142 TI - The development of a national children's formulary. AB - The British National Formulary has been in existence for over 30 years. The prescribing of medicines for children has been less well organized. Many medicines used in children have never been tested in the appropriate age groups and have been prescribed 'off-label'. This has led to safety issues and concerns that children continued to be treated as second-class citizens. The first attempt at the development of a national formulary specifically for prescribing in children occurred in 1999 with the publication of 'Medicines for Children'. This generated much national and international interest resulting in the government agreeing to fund the development and production of the first British National Formulary for Children in 2005. This article charts the process and progress of the formulary to the present day. PMID- 24215143 TI - The relationship between sub-clinical obsessive-compulsive symptoms and social cognition in chronic schizophrenia. AB - OBJECTIVES: Comorbid obsessive-compulsive (OC) symptoms in individuals with a primary diagnosis of schizophrenia are related to poorer cognitive performance and functional outcomes, but no study to date has assessed whether this comorbidity might also have implications for social cognition. The aim of the present study was to provide the first test of this possibility. DESIGN AND METHODS: Individuals with schizophrenia (n = 34) and demographically matched non clinical controls (n = 44) were assessed on two of the most important aspects of social cognitive function (1) facial affect recognition and (2) theory of mind, alongside more standard measures of cognitive function. RESULTS: The presence of OC symptoms was related to poorer performance on some of the cognitive measures, as well as one of the social cognitive measures (facial affect recognition). However, these relationships disappeared after controlling for scores on more general indices of schizophrenia psychopathology. CONCLUSIONS: The presence of OC symptoms in schizophrenia is not only associated with increased cognitive impairment but also increased difficulties with at least some aspects of social cognitive function. However, these relationships appear to reflect the elevated levels of psychopathology seen in this cohort more generally, rather than being uniquely attributable to OC symptomatology. PMID- 24215144 TI - Interpersonal problems across anxiety, depression, and eating disorders: a transdiagnostic examination. AB - OBJECTIVES: Integrative models of psychopathology suggest that quality of interpersonal relationships is a key determinant of psychological well-being. However, there is a relative paucity of research evaluating the association between interpersonal problems and psychopathology within cognitive behavioural therapy. Partly, this may be due to lack of brief, well-validated, and easily interpretable measures of interpersonal problems that can be used within clinical settings. The aim of the present study was to evaluate the psychometric properties, factor invariance, and external validity of the Inventory of Interpersonal Problems 32 (IIP-32) across anxiety, depression, and eating disorders. METHODS: Two treatment-seeking samples with principal anxiety and depressive disorders (AD sample, n = 504) and eating disorders (ED sample, n = 339) completed the IIP-32 along with measures of anxiety, depression, and eating disorder symptoms, as well as quality of life (QoL). RESULTS: The previously established eight-factor structure of the IIP-32 provided the best fit for both the AD and ED groups, and was robustly invariant across the two samples. The IIP 32 also demonstrated excellent external validity against well-validated measures of anxiety, depression, and eating disorder symptoms, as well as QoL. CONCLUSION: The IIP-32 provides a clinically useful measure of interpersonal problems across emotional and ED. PMID- 24215145 TI - Why self-critical patients present with more severe eating disorder pathology: the mediating role of shame. AB - OBJECTIVES: Gilbert (Compassion: Conceptualisations, Research, and Use in Psychotherapy. London: Routledge, 2005) theorized that self-critical individuals have more severe psychopathology due in part to their elevated feelings of shame. We sought to test this model in a sample of eating disorder sufferers. METHOD: Seventy-four patients admitted to a specialized day or inpatient eating disorders treatment programme completed the Forms of Self-Criticism and Self-Reassurance Scale, Rosenberg Self-Esteem Inventory, Experience of Shame Scale, Beck Depression Inventory, Positive and Negative Affect Schedule, and Eating Disorder Examination Questionnaire. RESULTS: We tested our mediational model with Preacher and Hayes' (Behavior Research Methods, 40, 879, 2008) bootstrapping approach entering self-criticism as a predictor, self-esteem as a covariate, and shame, negative affect, positive affect, and depressive symptoms as simultaneous mediators. Applying a 95% confidence interval, the total indirect effect of self criticism on eating disorder pathology was significantly different from zero suggesting that its influence occurred through the proposed set of mediators. Specific indirect effects revealed that shame was the only mediator to contribute significantly to the model. CONCLUSIONS: Results support the theory that among eating disorder patients, higher self-criticism is associated with elevated eating disorder pathology through feelings of shame. Interventions that target the shame of self-critical patients might therefore facilitate their recovery. PMID- 24215146 TI - The contribution of shame to post-psychotic trauma. AB - OBJECTIVES: The current study examined shame in a clinical sample recovering from a first episode of psychosis by focusing on the contribution of different types of shame to post-psychotic trauma while controlling for current affective symptoms. DESIGN: The study used a cross-sectional correlational design. METHOD: Fifty individuals who met the criteria for a psychotic disorder whose acute psychotic symptoms were in remission completed measures of internal and external shame associated with psychosis, general shame, post-psychotic trauma, and depression. RESULTS: Post-psychotic trauma symptoms were correlated with internal and external shame associated with psychosis and general shame. However, the relation between post-psychotic trauma and external shame associated with psychosis remained after controlling for general shame and current affective symptoms. In addition, internal shame had a stronger association with depression. Thus, internal and external shame due to psychosis had different associations with different types of post-psychotic emotional dysfunction. CONCLUSIONS: The results support the importance of assessing shame as a multi-faceted construct and suggest that assessing shame directly associated with mental illness is a worthwhile endeavour. PMID- 24215147 TI - The mental health, emotional literacy, cognitive ability, literacy attainment and 'resilience' of 'looked after children': a multidimensional, multiple-rater population based study. AB - OBJECTIVES: Existing research studies suggest that children who are looked after by the State experience high levels of mental health difficulties and underachieve in many other domains. Few studies, however, aim to reflect the heterogeneity of these children and those who are performing well may be under represented in the findings. This study aims to provide a more representative picture, offering novel data on resilience. DESIGN: A multidimensional, multiple rater population-based study of looked after children. METHOD: The entire population of looked after children aged 7-15 years (n = 193) in one local authority was assessed in core domains; mental health, emotional literacy, cognitive ability and literacy attainment. Measures included the Strength and Difficulties questionnaire, Emotional Literacy Assessment and Intervention Inventory, and the British Ability Scales. The children's data were compared with general population norms and existing research studies. The incidence of resilience, defined by the fulfilment of positive exception criteria, was recorded. Children fulfilling positive exception criteria were then compared to the remaining children on key factors. RESULTS: The looked after children performed less well in all domains compared with general population norms. Sixteen per cent of children met the positive exception criteria. Positive performance on individual measures varied from 34% to 76%. A statistically significant association was found between positive exception classification and two factors; parental contact and mainstream schooling. CONCLUSIONS: In general terms, this study supports the findings of previous research studies. However, evidence of positive exceptions across and within all domains cautions against overgeneralization of findings. The findings also implicate parental contact and mainstream education in the promotion of resilience. PMID- 24215148 TI - Exploring change processes in compassion focused therapy in psychosis: results of a feasibility randomized controlled trial. AB - OBJECTIVES: Compassion focused therapy (CFT) was developed to stimulate capacities for soothing and affiliation to self and others as a way to regulate the threat system. This feasibility study aimed to assess the safety, the acceptability, the potential benefits, and associated change processes of using group CFT with people recovering from psychosis. DESIGN: A prospective, randomized, open-label, blinded end point evaluation design was used. METHOD: Forty adult patients with a schizophrenia-spectrum disorder were randomized to CFT plus treatment as usual (TAU; n = 22) or to TAU alone (n = 18). Group CFT comprised 16 sessions (2 hr each, 1 x week). Participants were assessed prior to randomization and at the end of treatment. Assessments included semi-structured interviews to elicit narratives of recovery from psychosis and self-report measures. At the end of treatment, participants were rated on the Clinical Global Impression Scale. Narratives were coded using the Narrative Recovery Style Scale to provide measures of change in compassion and avoidance. Change processes were correlated with changes in depression, personal beliefs about illness, fear of recurrence, and positive and negative affect. RESULTS: Group CFT was associated with no adverse events, low attrition (18%), and high acceptability. Relative to TAU, CFT was associated with greater observed clinical improvement (p < 0.001) and significant increases in compassion (p = 0.015) of large magnitude. Relative to TAU, increases in compassion in the CFT group were significantly associated with reductions in depression (p = 0.001) and in perceived social marginalization (p = 0.002). DISCUSSION: Findings support the feasibility of group CFT in psychosis and suggest that changes in compassion can be achieved, which appear to reduce depression in particular. This is the first randomized controlled evaluation of CFT. CONCLUSION: Compassion focused therapy appears as a safe, acceptable, promising, and evolving intervention for promoting emotional recovery from psychosis. PMID- 24215149 TI - Emotional differentiation and parental bonding in inpatients suffering from eating disorders. AB - OBJECTIVES: This study aimed (1) to determine whether inpatients with eating disorders (EDs) have difficulty differentiating their emotions and being aware of the emotions of others; (2) to investigate the link between actual skills in emotional awareness and the sense of self-efficacy concerning these skills; and (3) to assess the impact of the quality of parental bonding on patients' levels of emotional awareness. METHODS: A sample of 44 inpatients with EDs, including a subgroup of 25 patients with restricting type anorexia nervosa (AR) and a subgroup of 19 patients with purging symptoms (PUR), were compared with 37 controls. All participants completed measures on emotional awareness (using the Level of Emotional Awareness Scale [LEAS]), alexithymia (using the Toronto Alexithymia Scale-20 [TAS-20]), and parental bonding (using the Parental Bonding Inventory). RESULTS: Inpatients with EDs reported difficulties in identifying and describing their feelings when using the self-report questionnaire (TAS-20). However, using a performance-based instrument (LEAS), inpatients with ED exhibited no deficits in differentiating their emotional states, although AR patients experienced difficulties when differentiating the emotional states of others. Moreover, there was no significant association between the TAS-20 and the LEAS scores, suggesting that the two measurements provide insight into different aspects of emotional processing. Regression analyses showed that maternal care had a positive influence on emotional awareness in the AR subgroup, whereas maternal overprotection had a negative influence on emotional awareness in PUR subgroup. CONCLUSIONS: Inpatients with EDs do not present with deficits in personal emotional awareness despite their self-perception. AR patients showed deficits in the emotional awareness of others. In patients with EDs, perceived maternal bonding influenced the development of emotional awareness, and this influence was dependent on the type of ED. Psychotherapies that focus on maternal bonding and emotional communication within the family unit may enhance emotional awareness in patients with anorexia or subclinical eating pathologies as an alternative. PMID- 24215150 TI - Adolescent loneliness and psychiatric morbidity in Northern Ireland. AB - OBJECTIVE: Previous research has identified an association between loneliness and psychiatric morbidity, but many of the studies have been based on small convenience samples and have not always used standardized measures. AIMS AND METHODS: This study aimed to assess the association between standardized measures of loneliness and psychiatric morbidity using data from a large sample of adolescents from Northern Ireland (Young Life and Times Survey, 2011). A total of 1,434 participants completed the survey. RESULTS: The prevalence of loneliness and psychiatric morbidity was 15.6% and 28.4% respectively. A multivariate binary logistic regression was used to identify the significant correlates of psychiatric morbidity. Demographic and loneliness variables were entered as covariates and female gender and perceptions of familial poverty were significantly associated with GHQ caseness. Loneliness increased the likelihood of GHQ caseness by more than five times. CONCLUSIONS: Adolescent loneliness is significantly associated with psychiatric morbidity for Northern Irish adolescents. School-based screening and interventions to reduce loneliness may reduce the prevalence of loneliness. PMID- 24215151 TI - Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through suppressed release of inflammatory cytokines. AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leucocyte infiltration in affected joints. Despite significant therapeutic advances, a new targeted approach is needed. Our objective in this work was to investigate the anti-inflammatory effects of the Ras inhibitor farnesylthiosalicylic acid (FTS) on adjuvant-induced arthritis (AIA) in rats, an experimental model for RA. Following AIA induction in Lewis rats by intradermal injection of heat-killed Mycobacterium tuberculosis, rats were treated with either FTS or dexamethasone and assessed daily for paw swelling. Joints were imaged by magnetic resonance imaging and computerized tomography and analysed histologically. The anti-inflammatory effect of FTS was assessed by serum assay of multiple cytokines. After adjuvant injection rats demonstrated paw swelling, leucocyte infiltration, cytokine secretion and activation of Ras-effector pathways. Upon FTS treatment these changes reverted almost to normal. Histopathological analysis revealed that the synovial hyperplasia and leucocyte infiltration observed in the arthritic rats were alleviated by FTS. Periarticular bony erosions were averted. Efficacy of FTS treatment was also demonstrated by inhibition of CD4(+) and CD8(+) T cell proliferation and of interferon (IFN) gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-17 release. The Ras effectors PI3K, protein kinase B (AKT), p38, and extracellular-regulated kinase (ERK) were significantly attenuated and forkhead box protein 3 (FoxP3) transcription factor, a marker of regulatory T cells, was significantly increased. Thus, FTS possesses significant anti-inflammatory and anti-arthritic properties and accordingly shows promise as a potential therapeutic agent for RA. Its effects are apparently mediated, at least in part, by a decrease in proinflammatory cytokines. PMID- 24215152 TI - The psychometric properties of the sexual excitation/sexual inhibition inventory for women (SESII-W) within a Dutch population. AB - According to the dual control model, sexual arousal is dependent on the disposition for both sexual excitation (SE) and sexual inhibition (SI; Bancroft, 1999). Individual variability in sexual inhibition and sexual excitation could partly explain individual differences in sexual arousability and the likelihood of experiencing sexual problems (Bancroft, Graham, Janssen, & Sanders, 2009). The Sexual Excitation/Sexual Inhibition Inventory for Women (SESII-W) is a questionnaire developed to measure the factors sexual excitation and sexual inhibition (Graham, Sanders, & Milhausen, 2006). This study describes the validation of the Dutch version of the SESII-W in a sample of 445 women. Using confirmatory factor analysis, we determined that the eight lower-order factor model achieved adequate fit to the data. A decrement in fit was noted when the two higher-order factors SE and SI were included in the model. The measure demonstrated good construct validity, internal consistency, and test-retest reliability. Furthermore, the scores of women with sexual problems differed from those without sexual problems, providing evidence for the discriminant validity of the SESII-W. PMID- 24215153 TI - Applanation pressure function in Goldmann tonometry and its correction. AB - So far applanation tonometry has not worked out any theoretical basis for correcting the result of intraocular pressure measurement carried out on a cornea with noncalibration dimensions by means of the Goldmann tonometer. All the tables of instrument reading corrections for cornea thickness or cornea curvature radius are based exclusively on measurements. This paper represents an attempt at creating a mechanical description of corneal apex deformation in Goldmann applanation tonometry. The functional dependence between intraocular pressure and the pressure exerted on the corneal apex by the tonometer was determined from a biomechanical model. Numerical GAT simulations, in which this function was also interrelated with the cornea's curvature radius and thickness were run and a constitutive equation for applanation tonometry, i.e. a full analytical description of intraocular pressure as a function of the above variables, was derived on this basis. The correction factors were defined and an algorithm for correcting the measured pressure was formulated. The presented formalism puts the results of experimental tonometry in new light. Analytical correction factors need not to come exclusively from measurements. A geometric interdependence between them and their dependence on pressure have been revealed. The theoretical description of applanation tonometry contained in the constitutive equation consists of a pressure function developed for a cornea with calibration dimensions and a coefficient correcting this calibration function, dependent exclusively on the cornea's actual thickness and curvature radius. The calibration function is a generalization of the Imbert-Fick law. PMID- 24215154 TI - Constitutive expression of HCA(2) in human retina and primary human retinal pigment epithelial cells. AB - PURPOSE/AIM: HCA2, a receptor of beta-hydroxybutyrate and niacin, has recently been described in mouse retina and immortalized human retinal pigment epithelial (RPE) cell lines. As HCA2 might be a pharmacologic target, e.g. in diabetic retinopathy, we studied its expression in human retina and primary human RPE cells. MATERIALS AND METHODS: Paraffin sections of human retina and primary human RPE cells were obtained from human donor eyes. Expression of HCA2 in human retina was investigated by immunohistochemistry of paraffin sections and by RT-PCR. HCA2 expression in primary human RPE cells was examined by immunocytochemistry and by Western-blot analysis. RESULTS: Positive immunohistochemical staining for HCA2 was found in paraffin sections of human retina, and positive immunocytochemical staining for HCA2 in primary human RPE cells. RT-PCR analysis detected mRNA expression of HCA2 in human retina. The expression of HCA2 protein was found in primary human RPE cells. CONCLUSIONS: Based on these results, HCA2 appears to be constitutively expressed in human retina and in primary human RPE cells. Although its functional role is still unknown, HCA2 may be potentially involved in the pathogenesis of various retinopathies and may offer a new therapeutic target. PMID- 24215155 TI - Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. AB - Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment have been produced by the Japan Gastroenterological Endoscopy Society in collaboration with the Japan Circulation Society, the Japanese Society of Neurology, the Japan Stroke Society, the Japanese Society on Thrombosis and Hemostasis and the Japan Diabetes Society. Previous guidelines from the Japan Gastroenterological Endoscopy Society have focused primarily on prevention of hemorrhage after gastroenterological endoscopy as a result of continuation ofantithrombotic therapy, without considering the associated risk of thrombosis. The new edition of the guidelines includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with withdrawal of antithrombotic therapy. PMID- 24215156 TI - "Homeopathic" palladium nanoparticle catalysis of cross carbon-carbon coupling reactions. AB - Catalysis by palladium derivatives is now one of the most important tools in organic synthesis. Whether researchers design palladium nanoparticles (NPs) or nanoparticles occur as palladium complexes decompose, these structures can serve as central precatalysts in common carbon-carbon bond formation. Palladium NPs are also valuable alternatives to molecular catalysts because they do not require costly and toxic ligands. In this Account, we review the role of "homeopathic" palladium catalysts in carbon-carbon coupling reactions. Seminal studies from the groups of Beletskaya, Reetz, and de Vries showed that palladium NPs can catalyze Heck and Suzuki-Miyaura reactions with aryl iodides and, in some cases, aryl bromides at part per million levels. As a result, researchers coined the term "homeopathic" palladium catalysis. Industry has developed large-scale applications of these transformations. In addition, chemists have used Crooks' concept of dendrimer encapsulation to set up efficient nanofilters for Suzuki Miyaura and selective Heck catalysis, although these transformations required high PdNP loading. With arene-centered, ferrocenyl-terminated dendrimers containing triazolyl ligands in the tethers, we designed several generations of dendrimers to compare their catalytic efficiencies, varied the numbers of Pd atoms in the PdNPs, and examined encapsulation vs stabilization. The catalytic efficiencies achieved "homeopathic" (TON = 540 000) behavior no matter the PdNP size and stabilization type. The TON increased with decreasing the Pd/substrate ratio, which suggested a leaching mechanism. Recently, we showed that water soluble arene-centered dendrimers with tri(ethylene glycol) (TEG) tethers stabilized PdNPs involving supramolecular dendritic assemblies because of the interpenetration of the TEG branches. Such PdNPs are stable and retain their "homeopathic" catalytic activities for Suzuki-Miyaura reactions for months. (TONs can reach 2.7 * 10(6) at 80 degrees C for aryl bromides and similar values for aryl iodides at 28 degrees C.) Sonogashira reactions catalyzed by these PdNPs are quantitative with only 0.01% Pd/mol substrate. Kato's group has reported remarkable catalytic efficiencies for mesoporous catalysts formed by polyamidoamine (PAMAM) dendrimer polymerizations. These and other mesoporous structures could allow for catalyst recycling, with efficiencies approaching the "homeopathic" behavior. In recent examples of Suzuki-Miyaura reactions of aryl chlorides, chemists achieved truly "homeopathic" catalysis when a surfactant such as a tetra-n-butylammonium halide or an imidazolium salt was used in stoichiometric quantities with substrate. These results suggest that the reactive halide anion of the salt attacks the neutral Pd species to form a palladate. In the case of aryl chlorides, the reaction may occur through the difficult, rate limiting oxidative-addition step. PMID- 24215157 TI - Improved virological suppression in children on antiretroviral treatment receiving community-based adherence support: a multicentre cohort study from South Africa. AB - Adherence to antiretroviral treatment (ART) is a challenge in childhood, and children on ART have reduced virological suppression compared to adults. This study evaluated the effect of community-based adherence support (CBAS) on virological outcomes amongst children receiving ART in four South African provinces. Patient Advocates are lay CBAS workers who provide adherence and psychosocial support for patients, undertaking home visits to address household challenges affecting adherence. Patient Advocates provide counselling for children's carers regarding adherence and psychosocial problems. A multicentre cohort study using routinely collected data was conducted at 57 public ART sites including ART-naive children (<16 years) starting ART. Virological suppression until four years of ART was compared between children who received and did not receive CBAS. Analyses were by intention-to-treat, controlling for confounding using multivariable generalised estimating equations. A total of 4853 children were included, of whom 982 (20.2%) received CBAS. The median baseline age was 6.3 years and the baseline CD4 cell percentage was 12.0%; both were equivalent between the two groups. CBAS children had more advanced baseline clinical disease (62.1% vs. 52.6% World Health Organisation stages III or IV; P < 0.0001). A total of 5908 viral load results were analysed. Virological suppression was 65.6% (95% confidence interval [CI]: 62.7-68.4%) vs. 55.5% (95% CI: 54.1-57.0%) in CBAS and non-CBAS children, respectively, at any time-point on treatment (P < 0.0001). In analyses controlling for baseline clinical, demographic, site-related variables and time on ART, children receiving CBAS were more likely to achieve virological suppression, adjusted odds ratio (aOR) 1.60 (95% CI: 1.35-1.89; P < 0.0001). The effect of CBAS increased in magnitude with increasing durations of ART, and CBAS particularly improved virological suppression in a higher-risk subgroup (children younger than two years, aOR 2.47 [95% CI: 1.59-3.84]). CBAS was associated with improved virological suppression in children receiving ART. Expanded implementation of this low-cost intervention should be considered in resource poor settings. PMID- 24215158 TI - Immunotherapeutic strategies for the treatment of renal cell carcinoma: where are we now? AB - Immunotherapy with cytokines was the first effective treatment in metastatic renal cell carcinoma (mRCC). Long-term responders and complete remissions were observed, but efficacy in the overall population was limited with the consequence that targeted agents replaced cytokines. The discovery of tumor associated antigens as direct targets paved the way from theses rather unspecific to specific immunotherapeutic strategies, which are discussed in this review. Autologous or dendritic cell (DC) based tumor vaccination with vitespen or AGS 003, adoptive T-cell transfer and synthetic peptide vaccination with IMA901 are new and promising approaches. Besides that the more passive strategies of antibody dependent cytotoxicity with the VEGF antibody bevacizumab or the carbonic anhydrase IX antibody girentuximab are discussed. Immunomodulation by cyclophosphamide, tyrosine kinase inhibitors or nivolumab, which targets the PD-1 axis, further promote T-cell activation and combinatory strategies with these agents are outlined. PMID- 24215159 TI - Attachment security in young foster children: continuity from 2 to 3 years of age. AB - The present study investigated attachment patterns among 60 foster children (FC) and 42 comparison children (CC) at 2 years (T1) and again at 3 years (T2) of age, as well as stability from T1 to T2. Descriptive analyses, including cross tabulation, were used to present attachment patterns, group differences and stability from T1 to T2. Most FC were securely attached at T1, and no group differences were identified; neither the FC nor CC differed from typical children in their attachment patterns. Furthermore, the majority of children in both groups received the same classification at both time points. Among FC who were securely attached at T1, a majority remained so at T2, while among those classified as disorganized at T1, significantly less remained so at T2. The study suggests that young FC have the possibility to form enduring secure attachments when placed in stable and well-functioning foster homes. PMID- 24215160 TI - Measurement of factor IX activity in plasma-derived and recombinant concentrates: insights from thrombin generation and activation-based assays. AB - BACKGROUND: Hemophilia B, resulting from a deficiency of coagulation factor IX, is treated effectively with either recombinant FIX (r-FIX) or plasma-derived FIX (pd-FIX) concentrates, although differences in pharmacokinetics are observed. FIX is activated in vivo by both activated FXI (FXIa) and tissue factor (TF) activated FVII (FVIIa); however, conventional activated partial thromboplastin time (APTT)-based assays assess only activation by FXIa. OBJECTIVES: To examine the differences between pd-FIX and r-FIX concentrates with respect to their thrombogenicity and activation. METHODS AND RESULTS: FIX ELISA was used to quantify antigenic FIX. Calibrated automated thrombography was performed to evaluate the effect of FIX on thrombin generation. FIXa was quantified by the cleavage of FIXa-specific chromogenic substrate. FIX activation was studied in a purified system. RESULTS: We found that r-FIX had ~ 1.6-fold greater specific activity than pd-FIX. r-FIX generated a markedly higher thrombin peak than pd-FIX at an equivalent antigen level when coagulation was initiated by TF, but this was not seen in contact activation-triggered thrombin generation (TG). Interestingly, the amount of FIXa in r-FIX concentrate was 10 times higher than that in pd-FIX concentrate. In a purified system, the amount of r-FIXa generated by FXIa in the first 10 min of activation was 1.37-fold that of pd-FIXa, whereas no difference between the concentrates was observed when triggered by TF-FVIIa. CONCLUSIONS: Clear differences were observed between pd-FIX and r-FIX concentrates, including the proportion of FIXa and the activation by FXIa. These may explain some of the discrepancies observed clinically, and suggest that the APTT may not reflect their resultant in vivo properties. PMID- 24215161 TI - Whole genome comparative analysis of channel catfish (Ictalurus punctatus) with four model fish species. AB - BACKGROUND: Comparative mapping is a powerful tool to study evolution of genomes. It allows transfer of genome information from the well-studied model species to non-model species. Catfish is an economically important aquaculture species in United States. A large amount of genome resources have been developed from catfish including genetic linkage maps, physical maps, BAC end sequences (BES), integrated linkage and physical maps using BES-derived markers, physical map contig-specific sequences, and draft genome sequences. Application of such genome resources should allow comparative analysis at the genome scale with several other model fish species. RESULTS: In this study, we conducted whole genome comparative analysis between channel catfish and four model fish species with fully sequenced genomes, zebrafish, medaka, stickleback and Tetraodon. A total of 517 Mb draft genome sequences of catfish were anchored to its genetic linkage map, which accounted for 62% of the total draft genome sequences. Based on the location of homologous genes, homologous chromosomes were determined among catfish and the four model fish species. A large number of conserved syntenic blocks were identified. Analysis of the syntenic relationships between catfish and the four model fishes supported that the catfish genome is most similar to the genome of zebrafish. CONCLUSION: The organization of the catfish genome is similar to that of the four teleost species, zebrafish, medaka, stickleback, and Tetraodon such that homologous chromosomes can be identified. Within each chromosome, extended syntenic blocks were evident, but the conserved syntenies at the chromosome level involve extensive inter-chromosomal and intra-chromosomal rearrangements. This whole genome comparative map should facilitate the whole genome assembly and annotation in catfish, and will be useful for genomic studies of various other fish species. PMID- 24215162 TI - Multiple magnetic mode-based Fano resonance in split-ring resonator/disk nanocavities. AB - Plasmonic Fano resonance, enabled by the weak interaction between a bright super radiant and a subradiant resonance mode, not only is fundamentally interesting, but also exhibits potential applications ranging from extraordinary optical transmission to biosensing. Here, we demonstrate strong Fano resonances in split ring resonators/disk (SRR/D) nanocavities. The high-order magnetic modes are observed in SRRs by polarization-resolved transmission spectroscopy. When a disk is centered within the SRRs, multiple high-order magnetic modes are coupled to a broad electric dipole mode of SRR/D, leading to significant Fano resonance spectral features in near-IR regime. The strength and line shape of the Fano resonances are tuned through varying the SRR split-angle and interparticle distance between SRR and disk. Finite-difference-time-domain (FDTD) simulations are conducted to understand the coupling mechanism, and the results show good agreement with experimental data. Furthermore, the coupled structure gives a sensitivity of ~282 nm/RIU with a figure of merit ~4. PMID- 24215163 TI - Assessing National Institutes of Health funding and scholarly impact in neurological surgery. AB - OBJECT: Research productivity is increasingly important in academic neurological surgery and can be measured through a variety of methods, such as publications, objective bibliometrics, and securing external grant support. The authors' objectives were to determine whether there is an association between scholarly impact, as measured by the h index, and successful National Institutes of Health (NIH) grant funding awarded to faculty in neurological surgery departments. METHODS: Primary investigators receiving National Institutes of Health (NIH) awards from Fiscal Years 2011-2013 were organized by academic rank, terminal degree, and their h index, as calculated from the Scopus database. These data were also obtained for nonfunded faculty from 15 randomly selected departments for comparison, and the average h index for each group was calculated. RESULTS: National Institutes of Health-funded faculty had higher average h indices than their nonfunded colleagues (23.6 vs 10.8, p < 0.0001), a finding that persisted upon controlling for academic rank. The mean h index increased with successive academic rank in both cohorts; greater funding totals were seen with successive academic position (Kruskal-Wallis, p < 0.05). National Institutes of Health funded MDs had higher h indices than their PhD colleagues (p = 0.04), although funding levels did not differ significantly. There was a trend of increasing h index with higher NIH-funding ranges (p < 0.05). CONCLUSIONS: The authors' findings demonstrate a strong relationship between scholarly impact and securing NIH funding among faculty in academic neurosurgical departments. Faculty receiving a greater amount of funding tended to have a higher h index. Mean scholarly impact, as measured by the h index, increased with successive academic rank among both NIH-funded and nonfunded faculty, suggesting that this bibliometric may have utility as an adjunct in the academic appointment and promotion process in academic neurological surgery. PMID- 24215164 TI - Use of D-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women. PMID- 24215165 TI - Osmotically controlled pulsatile release capsule of montelukast sodium for chronotherapy: statistical optimization, in vitro and in vivo evaluation. AB - The purpose of present study was to design, optimize and evaluate osmotically controlled pulsatile release capsule (PRC) of montelukast sodium (MKS) for the prevention of episodic attack of asthma in early morning and associated allergic rhinitis. Assembly of the capsular systems consisted of push, active and plug tablet arranged from bottom to top in hard gelatin capsule. The capsule system was coated with a semi-permeable membrane of cellulose acetate and drilled towards plug side in cap. A three-factor, three-level central composite design (CCD) with alpha = 1 was introduced to execute the experiments and quadratic polynomial model was generated to predict and assess the independent variables with respect to the dependent variables. The composition of optimal formulation was determined as weight of push tablet 138 mg (coded value: +0.59), plug tablet 60 mg (coded value: +0.49) and coating weight gain of 8.4 mg (coded value: 0.82). The results showed that the optimal formulation of PRCs had lag time of 4.5 h, release at 6 and 12 h are 61.95% and 96.29%, respectively. The X-ray radiographic imaging study was carried out to monitor the in vivo behavior of developed barium sulfate-loaded PRCs in rabbits under fasting conditions. In vivo pharmacokinetic study revealed Tmax of 2 h for marketed tablets; however 7 h for PRCs with initial lag time of 4 h. Thus designed capsular system may be helpful for patients with episodic attack of asthma in early morning and associated allergic rhinitis. PMID- 24215166 TI - Anhydrous proton conducting materials based on sulfonated dimethylphenethylchlorosilane grafted mesoporous silica/ionic liquid composite. AB - Efficient membrane proton conductivity at elevated temperatures (>100 degrees C) and reduced humidification conditions is a critical issue hindering fuel cell commercialization. Herein, proton conducting materials consisting of high surface area acid catalyzed mesoporous silica functionalized with sulfonated dimethylphenethylchlorosilane was investigated under anhydrous conditions. The organic moiety covalently bonded to the silica substrate via active hydroxyl groups on the silica pore surface. The structure and dynamic phases of the attached organic molecule were characterized and qualitatively determined by XRD, TEM, FT-IR, and solid state NMR. The amount of grafted organic molecules was estimated to be 2.45 MUmol m(-2) by carbon elemental analysis. The so-formed composite materials showed adequate thermal stability up to 300 degrees C as determined by TGA. Under anhydrous conditions, ionic conductivity of the composite material upon ionic liquid impregnation reaches a peak value of 1.14 * 10(-2) S cm(-1) at 160 degrees C associated with the activation energy of 9.24 kJ mol(-1) for proton transport. PMID- 24215167 TI - The cultural context of nondisclosure of alcohol-involved acquaintance rape among Asian American college women: a qualitative study. AB - With high college enrollment and increasing alcohol use, Asian American (AA) college women may be at particular risk for experiencing alcohol-involved acquaintance rape. Although AA women have expressed the weakest intentions to report rape when compared to other ethnic groups, cultural factors influencing these intentions remain unexamined. Guided by grounded theory, 17 self-identified AA college women were interviewed about how the average AA college woman would respond to an alcohol-involved acquaintance rape. Despite awareness of benefits of disclosing rape, participants emphasized that nondisclosure would be the normative response. Three themes emerged from participants: institutional, sociocultural, and psychological contexts of nondisclosure. At an institutional level, nondisclosure referenced mental health and police services, which included Asian stereotypes and mistrust of police. Within a sociocultural context, rape nondisclosure focused on negative consequences on relationships with parents and, to a lesser extent, on friendships. Emotional avoidance and not labeling an acquaintance rape as rape were psychological strategies for rape nondisclosure. Participant's conceptualizations of mental and physical health concerns, specifically post-rape concerns, were framed within sociocultural/macrostructural contexts and may not match that of the more individualistic U.S. mainstream conceptualizations of health. Culturally sensitive rape education may be more effective in increasing rape prevention and support. PMID- 24215169 TI - Ocular sparganosis mimicking an orbital idiopathic inflammatory syndrome. AB - Sparganosis is an infection by the parasitic tapeworm larvae of Spirometra species. Ocular sparganosis is a rare disease that is easily misdiagnosed. We reported a rare case of ocular sparganosis mimicking orbital idiopathic inflammatory syndrome at initial presentation. A 34-year-old female presented with rapid progressive swelling of her left eyelid and mild proptosis for the duration of one month. The other ocular examinations were normal and the thyroid function was normal. Magnetic resonance imaging revealed a fusiform enlargement and mild heterogenous enhancement of the superior oblique muscle of the left orbit. First she received prednisolone therapy and the proptosis partially improved. Six months later, a white, flat and wrinkled string like worm wriggled out from the caruncular conjunctiva of the left eye. The pathology results confirmed that the worm was a Spirometra species larva. After removal of the larva and treatment with praziquantel, the proptosis was resolved without recurrence. Ocular sparganosis is a rare disease and only a few case reports have been reported. The drug therapy has not been effective and the surgical removal is the principal therapy. Despite its rarity, ocular sparganosis should be considered as a possible cause of orbital inflammation in patients. PMID- 24215168 TI - A myelopoiesis gene signature during remission in anti-neutrophil cytoplasm antibody-associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy. AB - A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti-neutrophil cytoplasm antibody-associated vasculitis (AAV), and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors [CCAAT/enhancer binding protein alpha (CEBP alpha), CCAAT/enhancer binding protein beta (CEBP-beta), SPI1/PU.1-related transcription factor (SPIB), spleen focus forming virus proviral integration oncogene, PU.1 homologue (SPI1)] and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were analysed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMC, PMN) and MPO (PBMC). PR3 and SPIB mRNA correlated positively in controls but negatively in patient PBMC. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses, but correlated with steroid treatment. Prednisolone doses were negatively linked to SPIB and miR-155-5p, miR-339-5p (PBMC) and to miR-221, miR 361 and miR-505 (PMN). PR3 mRNA in PBMC correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multi-factorial, but to an important extent explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly. PMID- 24215170 TI - Role of nitric oxide synthase genes in hepatitis E virus infection. AB - Hepatitis E virus (HEV) is the most common cause of endemic and epidemic acute hepatitis. A correlation between iNOS, eNOS polymorphisms, levels and severity of disease has been reported, and here, we examined the role of iNOS and eNOS gene polymorphisms and their levels in HEV-related acute viral hepatitis and acute liver failure. Hepatitis E virus-related cases of acute hepatitis (294 patients) and liver failure (82 patients) and age- and sex-matched healthy controls (331 subjects) were included in the study. PCR-RFLP was performed to identify the polymorphisms in the iNOS and eNOS genes. iNOS and eNOS levels were studied using ELISA assays and HEV viral load, genotype and combined effects of iNOS genotype, levels and parameters for disease severity were examined. The frequency of iNOS (CT + TT) and eNOS (GT + TT) genotypes was higher in subjects with liver failure compared with controls. iNOS and eNOS levels in patients with acute liver failure (55.51 +/- 6.33 IU/mL, 60.2 +/- 3.69) cases were significantly increased as compared to patients with acute viral hepatitis (17.8 +/- 6.08 IU/mL, 23.7 +/- 6.57) and controls (P < 0.05). A significant positive correlation was observed between the iNOS and eNOS levels in our study population when compared with the severity of disease parameters. Hence, the iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure. This study supports the possible role of nitric oxide synthase genes (iNOS and eNOS) in determining the severity of HEV infection. PMID- 24215171 TI - The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers. AB - AIMS: ABT-288 is a potent and selective H3 receptor antagonist with procognitive effects in several preclinical models. In previous studies, 3 mg once daily was the maximal tolerated dose in healthy volunteers. This study characterized the safety, tolerability and pharmacokinetics of ABT-288 in stable subjects with schizophrenia. METHODS: This was a randomized, double-blind, placebo-controlled, dose-escalating study of ABT-288 (10 dose levels, from 1 to 60 mg once daily for 14 days) in stable subjects with schizophrenia treated with an atypical antipsychotic. In each dose group, five to seven and two to three participants were assigned to ABT-288 and placebo, respectively. RESULTS: Of the 67 participants enrolled, nine participants (on ABT-288) were prematurely discontinued, in seven of these due to adverse events. ABT-288 was generally safe and tolerated at doses up to 45 mg once daily. The most common adverse events, in decreasing frequency (from 31 to 5%), were abnormal dreams, headache, insomnia, dizziness, somnolence, dysgeusia, dry mouth, psychotic disorder, parosmia and tachycardia. Adverse events causing early termination were psychotic events (four) and increased creatine phosphokinase, pyrexia and insomnia (one each). The half-life of ABT-288 ranged from 28 to 51 h, and steady state was achieved by day 12 of dosing. At comparable multiple doses, ABT-288 exposure in subjects with schizophrenia was 45% lower than that previously observed in healthy subjects. At trough, ABT-288 cerebrospinal fluid concentrations were 40% of the total plasma concentrations. CONCLUSIONS: ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake. PMID- 24215172 TI - The prevalence and contents of advance directives in patients with pacemakers. AB - BACKGROUND: Little is known about the use of advance directives (ADs) in patients who have implantable cardiac pacemakers (PMs). METHODS: We conducted a retrospective review of the medical records of residents of Olmsted County, Minnesota, who underwent implantation of a cardiac PM at Mayo Clinic (Rochester, Minnesota) during 2006 and 2007, and determined the prevalence and contents of ADs in these patients. RESULTS: During the study period, 205 residents of Olmsted County (men, 53%) underwent PM implantation (mean age [standard deviation] at implantation, 77 [15] years). Overall, 120 patients (59%) had ADs. Of these, 63 ADs (53%) were executed more than 12 months before and 33 (28%) were executed after PM implantation. Many patients specifically mentioned life-prolonging treatments in their ADs: cardiopulmonary resuscitation, 76 (63%); mechanical ventilation, 56 (47%); and hemodialysis, 31 (26%). Pain control was mentioned in 79 ADs (66%) and comfort measures were mentioned in 42 ADs (35%). Furthermore, the AD of many patients contained a general statement about end-of-life care (e.g., no "heroic measures"). However, only one AD (1%) specifically addressed the end-of-life management of the PM. CONCLUSIONS: More than half of the patients with PMs in our study had executed an AD, but only one patient specifically mentioned her PM in her AD. These results suggest that patients with PMs should be encouraged to execute ADs and specifically address end-of-life device management in their ADs. Doing so may prevent end-of-life ethical dilemmas related to PM management. PMID- 24215173 TI - Physical inactivity prevalence and trends among Mexican adults: results from the National Health and Nutrition Survey (ENSANUT) 2006 and 2012. AB - BACKGROUND: Lifestyles such as unhealthy diets and the lack of physical activity have been contributed to the increased prevalence of obesity. In 2012, the world health organization published the first global recommendation for physical activity and health. People who do not meet at least 150 minutes of moderate-to vigorous physical activity are considered to be physically inactive. The prevalence of physical inactivity worldwide is 31%, however there is insufficient data from prevalence and trends of physical inactivity in Mexican population. The purposes of this study are to describe the physical inactivity prevalence and recent trends in Mexican adults and to examine the association between physical inactivity with biologic and sociodemographic characteristics. METHODS: Representative samples of 17,183 and 10,729 adults (aged 20 to 69 years) who participated in the National Health and Nutrition Survey (ENSANUT) in 2006 and 2012, respectively. Moderate-to-vigorous physical activity (MVPA) was assessed using the short form version of the International Physical Activity Questionnaire (IPAQ), which was administered in face-to-face interviews. Self-reported IPAQ MVPA levels were adjusted using an equation derived from a previous validation study. Participants were considered inactive if they engaged in <150-minutes/week of moderate physical activity or <75 minutes/week of vigorous physical activity according to WHO classification criteria. RESULTS: The prevalence of physical inactivity was significantly higher in 2012 (19.4%, 95% CI: 18.1, 20.7) than in 2006 (13.4%, 95% CI: 12.5, 14.5). Adults in the obese category, 60-69 age group, and those in the highest socioeconomic status tertile were more likely to be physically inactive. CONCLUSIONS: The proportion of the Mexican adult population who do not meet the minimum WHO physical activity criteria has increased by 6% points between 2006 and 2012. Given the increasing prevalence of obesity, the aging of the population, and the shift in socioeconomic status in Mexico, physical inactivity could continue to increase in the coming years unless effective public health interventions are implemented. PMID- 24215174 TI - Exposure of pregnant women to cookstove-related household air pollution in urban and periurban Trujillo, Peru. AB - Although evidence suggests associations between maternal exposure to air pollution and adverse birth outcomes, pregnant women's exposure to household air pollution in developing countries is understudied. Personal exposures of pregnant women (N = 100) in Trujillo, Peru, to air pollutants and their indoor concentrations were measured. The effects of stove-use-related characteristics and ambient air pollution on exposure were determined using mixed-effects models. Significant differences in 48-hour kitchen concentrations of particulate matter (PM2.5), carbon monoxide (CO), and nitrogen dioxide (NO2) concentrations were observed across fuel types (p < 0.05). Geometric mean PM2.5 concentrations where 112 MUg/m(3) (confidence limits [CLs]: 52, 242 MUg/m(3)) and 42 MUg/m(3) (21, 82 MUg/m(3)) in homes where wood and gas were used, respectively. PM2.5 exposure was at levels that recent exposure-response analyses suggest may not result in substantial reduction in health risks even in homes where cleaner burning gas stoves were used. PMID- 24215175 TI - Vision-related quality of life tends to be more severely impaired in patients with dysthyroid optic neuropathy. AB - PURPOSE: Dysthyroid optic neuropathy (DON) is the most severe condition in thyroid eye disease (TED); however, no study has been conducted to assess quality of life in these patients to date. The aim of this study was to evaluate vision related quality of life in TED patients with DON using a Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (CHI-VFQ-25). METHODS: The CHI-VFQ-25 scores were compared for 23 TED patients with DON and 13 TED patients without DON. The correlations between the clinical characteristics and subscale scores on the CHI-VFQ-25 and the floor and ceiling effects of the CHI-VFQ-25 were also assessed. RESULTS: Patients with DON scored significantly lower than patients without DON on the CHI-VFQ-25 (composite score: 54 versus 77, respectively, p = 0.001). Many subscales were significantly correlated with the severity and activity of the disease (p < 0.05). In patients with DON, no floor effects were found, and ceiling effects were only observed for Color vision, Peripheral vision and Social function. Role limitations and Mental health were the lowest scores in all the subscales. CONCLUSIONS: The current study showed that vision-related quality of life tended to be more severely impaired in TED patients with DON than in patients without DON. The CHI-VFQ-25 may be a promising tool to estimate the benefits of interventions in patients with DON. PMID- 24215176 TI - Relationship between small cerebral white matter lesions and cognitive function in patients with Alzheimer's disease and amnestic mild cognitive impairment. AB - AIM: The main purpose of the present study was to investigate the influence of small cerebral white matter lesions on cognitive functions, and its difference by clinical stage. METHODS: A total of 160 patients with Alzheimer's disease and 40 older adults with amnestic mild cognitive impairment were enrolled in the present study. The Fazekas rating scale was used for the semi-quantitative measurement of white matter lesions. Participants whose scales were more than grade 2 were excluded. Associations between the degree of small white matter lesions and cognitive functions including memory, verbal fluency, working memory, processing speed, and executive function were examined. RESULTS: We found that small white matter lesions influenced the performances of neuropsychological tests differently between Alzheimer's disease and amnestic mild cognitive impairment. Analysis of covariance showed significant effects of interaction on a test that assessed categorical verbal fluency. In the amnestic mild cognitive impairment group, small periventricular white matter hyperintensities were significantly associated with poor performances in categorical verbal fluency; whereas in the Alzheimer's disease group, such associations were not observed. Deep white matter hyperintensities did not influence any cognitive functions examined in both groups. CONCLUSIONS: The results suggested the involvement of periventricular small white matter lesions on impairment in verbal fluency, and such influence might be different depending on an individual's clinical stage. PMID- 24215177 TI - Hemodynamic impacts of left coronary stenosis: a patient-specific analysis. AB - This study analyses the hemodynamic variations surrounding stenoses located at the left coronary bifurcation, and their influence on the wall shear stress (WSS) in realistic coronary geometries. Four patients with suspected coronary artery disease were chosen, and coronary models were reconstructed based on high resolution CT data. The coronary stenoses were observed at the left circumflex and left anterior descending branches, resulting in a lumen narrowing of >50%. Flow analysis was performed using computational fluid dynamics, to simulate the cardiac flow conditions of the realistic individual patient geometry. Blood flow and WSS changes in the left coronary artery were calculated throughout the entire cardiac phases. Our results revealed that the recirculation regions were found at the poststenotic locations. WSS was found to increase at the stenotic positions in all four patients. There is a strong correlation between coronary stenosis and the hemodynamic changes, which are reflected in blood flow pattern and WSS, based on the realistic left coronary geometries. PMID- 24215179 TI - Structures and chemical properties of silicene: unlike graphene. AB - The discovery of graphene and its remarkable and exotic properties have aroused interest in other elements and molecules that form 2D atomic layers, such as metal chalcogenides, transition metal oxides, boron nitride, silicon, and germanium. Silicene and germanene, the Si and Ge counterparts of graphene, have interesting fundamental physical properties with potential applications in technology. For example, researchers expect that silicene will be relatively easy to incorporate within existing silicon-based electronics. In this Account, we summarize the challenges and progress in the field of silicene research. Theoretical calculations have predicted that silicene possesses graphene-like properties such as massless Dirac fermions that carry charge and the quantum spin Hall effect. Researchers are actively exploring the physical and chemical properties of silicene and tailoring it for wide variety of applications. The symmetric buckling in each of the six-membered rings of silicene differentiates it from graphene and imparts a variety of interesting properties with potential technological applications. The pseudo-Jahn-Teller (PJT) distortion breaks the symmetry and leads to the buckling in silicenes. In graphene, the two sublattice structures are equivalent, which does not allow for the opening of the band gap by an external electric field. However, in silicene where the neighboring Si atoms are displaced alternatively perpendicular to the plane, the intrinsic buckling permits a band gap opening in silicene in the presence of external electric field. Silicene's stronger spin orbit coupling than graphene has far reaching applications in spintronic devices. Because silicon prefers sp(3) hybridization over sp(2), hydrogenation is much easier in silicene. The hydrogenation of silicene to form silicane opens the band gap and increases the puckering angle. Lithiation can suppress the pseudo-Jahn-Teller distortion in silicene and hence can flatten silicene's structure while opening the band gap. So far, chemists have not successfully synthesized and characterized a free standing silicene. But recently chemists have successfully produced silicene sheets and nanoribbons over various substrates such as silver, diboride thin films, and iridium. The supporting substrate critically controls the electronic properties of silicene, and the match of the appropriate support and its use is critical in applications of silicene. PMID- 24215178 TI - Selective importance of the rat anterior thalamic nuclei for configural learning involving distal spatial cues. AB - To test potential parallels between hippocampal and anterior thalamic function, rats with anterior thalamic lesions were trained on a series of biconditional learning tasks. The anterior thalamic lesions did not disrupt learning two biconditional associations in operant chambers where a specific auditory stimulus (tone or click) had a differential outcome depending on whether it was paired with a particular visual context (spot or checkered wall-paper) or a particular thermal context (warm or cool). Likewise, rats with anterior thalamic lesions successfully learnt a biconditional task when they were reinforced for digging in one of two distinct cups (containing either beads or shredded paper), depending on the particular appearance of the local context on which the cup was placed (one of two textured floors). In contrast, the same rats were severely impaired at learning the biconditional rule to select a specific cup when in a particular location within the test room. Place learning was then tested with a series of go/no-go discriminations. Rats with anterior thalamic nuclei lesions could learn to discriminate between two locations when they were approached from a constant direction. They could not, however, use this acquired location information to solve a subsequent spatial biconditional task where those same places dictated the correct choice of digging cup. Anterior thalamic lesions produced a selective, but severe, biconditional learning deficit when the task incorporated distal spatial cues. This deficit mirrors that seen in rats with hippocampal lesions, so extending potential interdependencies between the two sites. PMID- 24215180 TI - Ultrafast excited-state dynamics and vibrational cooling of 8-oxo-7,8-dihydro-2' deoxyguanosine in D2O. AB - Nguyen and Burrows recently demonstrated that UV-B irradiation of 8-oxo-7,8 dihydro-2'-deoxyguanosine (8-oxodG), a signature product of oxidatively damaged DNA, can repair cyclobutane pyrimidine dimers in double-stranded DNA (J. Am. Chem. Soc. 2011, 133, 14586 - 14589). In order to test the hypothesis that repair occurs by photoinduced electron transfer, it is critical to determine basic photophysical parameters of 8-oxodG including the excited-state lifetime. Here, femtosecond transient absorption spectroscopy was used to study the ultrafast excited-state dynamics of 8-oxodG with excitation in the UV and probing at visible and mid-IR wavelengths. The excited-state lifetimes of both neutral and basic forms of 8-oxodG in D2O are reported for the first time by monitoring the disappearance of excited-state absorption at 570 nm. The lifetime of the first excited state of the neutral form is 0.9 +/- 0.1 ps, or nearly twice as long as that of 2'-deoxyguanosine. The basic form of 8-oxodG exhibits a much longer excited-state lifetime of 43 +/- 3 ps. Following ultrafast internal conversion by neutral 8-oxodG, a vibrationally hot ground state is created that dissipates its excess vibrational energy to the solvent on a time scale of 2.4 +/- 0.4 ps. Femtosecond time-resolved IR experiments provide additional insights into excited state dynamics and the vibrational relaxation of several modes in the fingerprint region. PMID- 24215181 TI - Synthesis of polyhydroxylated quinolizidines and azaspiro[4.5]decanes from D xylose. AB - The synthesis of novel polyhydroxylated quinolizidines and azaspiro[4.5]decanes is reported. A key step of this transformation involved an addition of allylmagnesium bromide to an omega-bromonitrile derived from D-xylose followed by an intramolecular displacement of a bromide. The resulting cyclic imine was treated either with allylmagnesium bromide or with NaBH4, to provide 2,2-diallyl- or 2-allylpiperidine, respectively. The desired bicyclic framework was constructed via a ring-closing metathesis reaction. The Ru catalysts were reused in the following syn-dihydroxylation step. PMID- 24215182 TI - A validation of the Experiences in Close Relationships-Relationship Structures scale (ECR-RS) in adolescents. AB - Emerging evidence points toward a two-dimensional attachment construct: avoidance and anxiety. The Experiences in Close Relationships-Relationship Structures scale (ECR-RS; Fraley, Heffernan, Vicary, & Brumbaugh, 2011) is a questionnaire assessing two-dimensional relationship-specific attachment structures in adults and, hence, moves beyond the traditional focus on romantic relationships. The present article explored the psychometric abilities of the ECR-RS across parental and best friend domains in a sample of 15 to 18-year-olds (n = 1999). Two oblique factors were revealed across domains, exhibiting satisfactory construct validity, including factor-specific links to the model of adult attachment (Bartholomew & Horowitz, 1991), and independent factor discrimination between subgroups. A robust validation supports the application of the ECR-RS to assessing relationship-specific adolescent attachment structures. PMID- 24215183 TI - HIV risk perception among pregnant women in western India: need for reducing vulnerabilities rather than improving knowledge! AB - Since the beginning of the HIV/AIDS epidemic in India, pregnant women attending antenatal clinics (ANC) have been considered as a low HIV risk population. Yet, a substantial proportion of new HIV infections are occurring among stable heterosexual couples. This paper sought to investigate the proportion and profile of women who, within the low-risk population, are potentially at higher risk of HIV infection. HIV risk perception of pregnant women enrolled within the ANRS 12127 Prenahtest trial was described and associated socio-behavioral characteristics, husband's characteristics, and HIV-related characteristics were analyzed using univariate and multivariate logistic regression models. Among 484 women enrolled, baseline data were collected for 479 women and 460 women with completed data were considered for the present analysis (96%). Eighty-nine (19.4%) women perceived themselves at risk of HIV. Women with educational level <11years (Adjusted Odds Ratio, AOR = 2.4 [CI = 1.28-4.53]), who stayed in joint families (AOR = 1.89 [CI = 1.12-3.12]), who had experienced insult or hurt from the partner (AOR = 1.91 [CI = 1.11-3.27]) and whose partner were alcoholic (AOR = 2.19 [CI = 1.31-3.66]) were significantly more likely to perceive themselves at risk of HIV. Women who had heard about sexually transmitted infections were also more likely to report HIV risk perception (AOR = 3.36 [CI = 1.83-6.18]). Substantial proportion of women (one out of five) perceived themselves at risk of HIV and most of these have reported some form of vulnerability in their couple relationship such as intimate partner violence, alcoholic partner, lack of communication, and spaces for communication with partner. Though awareness and knowledge is the first step for prevention, considering the vulnerabilities associated with HIV risk perception, HIV prevention interventions in India should target overall sources of vulnerability to HIV. Targeted risk reduction for women in ANC should be considered for primary HIV prevention among couples. PMID- 24215184 TI - Brain uptake of a fluorescent vector targeting the transferrin receptor: a novel application of in situ brain perfusion. AB - Monoclonal antibodies (mAbs) targeting blood-brain barrier (BBB) transporters are being developed for brain drug targeting. However, brain uptake quantification remains a challenge, particularly for large compounds, and often requires the use of radioactivity. In this work, we adapted an in situ brain perfusion technique for a fluorescent mAb raised against the mouse transferrin receptor (TfR) (clone Ri7). We first confirmed in vitro that the internalization of fluorolabeled Ri7 mAbs is saturable and dependent on the TfR in N2A and bEnd5 cells. We next showed that the brain uptake coefficient (Clup) of 100 MUg (~220 nM) of Ri7 mAbs fluorolabeled with Alexa Fluor 750 (AF750) was 0.27 +/- 0.05 MUL g(-1) s(-1) after subtraction of values obtained with a control IgG. A linear relationship was observed between the distribution volume VD (MUL g(-1)) and the perfusion time (s) over 30-120 s (r(2) = 0.997), confirming the metabolic stability of the AF750-Ri7 mAbs during perfusion. Co-perfusion of increasing quantities of unlabeled Ri7 decreased the AF750-Ri7 Clup down to control IgG levels over 500 nM, consistent with a saturable mechanism. Fluorescence microscopy analysis showed a vascular distribution of perfused AF750-Ri7 in the brain and colocalization with a marker of basal lamina. To our knowledge, this is the first reported use of the in situ brain perfusion technique combined with quantification of compounds labeled with near-infrared fluorophores. Furthermore, this study confirms the accumulation of the antitransferrin receptor Ri7 mAb in the brain of mice through a saturable uptake mechanism. PMID- 24215185 TI - Synteny analysis provides a route to design genus-specific PCR primers for rapid identification of all Saccharomyces species. AB - The genus Saccharomyces comprises seven single-genome species (S. arboricola, S. cerevisiae, S. eubayanus, S. kudriavzevii, S. mikatae, S. paradoxus and S. uvarum) and two hybrid species - S. pastorianus (S. cerevisiae plus S. eubayanus) and S. bayanus (mostly S. uvarum plus S. eubayanus). Species-specific primers have already been developed for the identification of each of the single-genome species, and these primers can usually detect both genomes in hybrids. It would be advantageous if a single reaction could detect any member of the clade. We have investigated three potentially generic approaches to design genus-specific primers. Two methods that both use sequence alignment differences for primer design were only partly successful. A third method used synteny data to identify 136 target genes that are potentially present only in all species of the Saccharomyces clade. HSP30 (YCR021C) was fully successful; different primer pairs were developed with high G+C content for use at 63 degrees C. In < 3 h, using a robust colony-PCR followed by gel electrophoresis, the method can reliably detect any member of the genus. This novel approach still uses conventional sequence alignment mismatches but relies principally on the presence of the target gene only within the genus Saccharomyces. PMID- 24215186 TI - Thrombosis in congenital heart disease. PMID- 24215188 TI - ICDs in adults with congenital heart disease: an overview. PMID- 24215187 TI - Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: ready for the prime time? PMID- 24215190 TI - Searching the place of pitavastatin in the current treatment of patients with dyslipidemia. AB - Pitavastatin is the last marketed statin. Different studies have shown that pitavastatin is more potent than pravastatin and simvastatin in reducing LDL cholesterol levels, and equivalent to atorvastatin and rosuvastatin. Moreover, pitavastatin provides a significant and sustained increase of HDL-cholesterol levels. Remarkably, as pitavastatin is minimally metabolized by CYP, the risk of interactions with other drugs is low. Additionally, pitavastatin does not interfere with glucose metabolism in diabetics and non-diabetics, and exerts a beneficial effect in patients with renal dysfunction. However, although available information may suggest that pitavastatin can improve cardiovascular prognosis, data coming from specifically designed clinical trials are still warranted. The aim of this review was to update the available evidence about efficacy and safety of pitavastatin, and to analyze the place of pitavastatin in the current armamentarium for the treatment of patients with hypercholesterolemia. PMID- 24215191 TI - Transapical access and closure devices: rationale and current status. AB - In the past years transcatheter aortic valve implantation became a highly standardized option for the treatment of high-risk patients suffering from severe aortic stenosis. The number of transcatheter aortic valve implantation procedures is increasing exponentially worldwide. In this context the transapical approach should be considered as a safe and reproducible alternative access to the left ventricle with some specific advantages compared with transfemoral, transaortic and transsubclavian approach due to its antegrade nature. To further ease the transapical access first apical closure devices have been developed and entered first clinical trials. PMID- 24215192 TI - Balancing bleeding and thrombotic risk with new oral anticoagulants in patients with atrial fibrillation. AB - Atrial fibrillation (AF) markedly increases the risk of stroke. Warfarin is highly effective for the prevention of stroke in such patients, but it is difficult to use and causes bleeding. Three new oral anticoagulants have been approved for stroke prevention in AF patients, and are at least as effective as warfarin with better bleeding profiles. These new agents have changed and simplified our approach to stroke prevention, as the threshold for initiation of oral anticoagulation is lower. All patients with AF should be risk assessed using the CHA2DS2-VASc score, and all patients with a score of 1 or above (except women with female sex as their only risk factor on the CHA2DS2-VASc score) should be considered for oral anticoagulation with one of the new agents. Formal bleeding risk assessment is essential, and can be done by using the well-validated HAS BLED score. PMID- 24215193 TI - Thrombolysis for iliofemoral deep venous thrombosis. AB - Patients with iliofemoral deep vein thrombosis (DVT) comprise a subset of patients with DVT who are at significant risk for developing the postthrombotic syndrome (PTS) following treatment with anticoagulation alone. PTS can have debilitating effects on patients' quality of life. Its symptoms range from pain and heaviness to venous ulceration. Treatment techniques that eliminate the thrombus burden from the lower extremity have been shown to reduce the incidence of postthrombotic symptoms by restoring venous patency to the iliofemoral venous system and preserving valvular function. Treatment techniques include operative thrombectomy, catheter-directed thrombolysis and pharmacomechanical thrombolysis. This paper focuses on the latter two techniques and reviews the evidence for adopting the strategy of thrombus removal in patients with iliofemoral DVT. PMID- 24215194 TI - Patient selection for thromboprophylaxis in medical inpatients. AB - Acutely ill medical patients may be at increased risk of venous thromboembolism, both during hospitalization and after discharge. International guidelines recommend thromboprophylaxis for high-risk medical patients with low bleeding risk for a maximum of 14 days. There are two approaches to identify the high-risk patient: adhering to the inclusion criteria used in randomized clinical trials or using risk assessment models. With both approaches, about 40% of medical inpatients should result at increased risk of venous thrombosis. However, in the real world, medical inpatients are more fragile than patients enrolled in clinical trials, and thus also require a careful assessment of the individual bleeding risk. The complex balance between risks and benefits of thromboprophylaxis has become particularly relevant in studies assessing extended prophylaxis beyond hospitalization in this setting. In the present review, we will summarize the most recent evidence on this topic. PMID- 24215195 TI - Should we anticoagulate after bioprosthetic aortic valve replacement? AB - There is a lack of consensus as to the ideal antithrombotic strategy after bioprosthetic aortic valve replacement. Herein, the authors review the literature on this topic and find that most of the evidence is comprised of small observational data, with a few prospective trials. The bulk of the evidence is in favor of no anticoagulation after bioprosthetic aortic valve replacement in patients at low risk of thromboembolism. Most studies suggest using only antiplatelet therapy with the exception of two studies that advocate anticoagulation. One study suggests that no antithrombotic therapy at all may be safe. One study evaluated the question mechanistically, showing no increased microembolic signals on transcranial Doppler in patients receiving aspirin compared to patients who were anticoagulated. Based on the evidence presented, the authors recommend using aspirin only after bioprosthetic aortic valve replacement in patients at low risk of thromboembolism. PMID- 24215196 TI - Role of imaging in interventions on structural heart disease. AB - Recent technological progresses have led to the development of new devices and procedures which have greatly improved the chance to effectively treat structural heart diseases in both children and adults. Interventional cardiology has been receiving fast and wide implementation as an effective alternative treatment to surgery for several congenital and acquired diseases. The advent of transcatheter valve implantation/repair techniques constitutes one of the main breakthroughs of the last decades. Such development and implementation is strictly related to a continuous progress in cardiac imaging as well. Indeed, multimodality cardiac imaging (such as X-ray, echocardiography, MRI, multidetector computed tomography) has become essential in providing accurate patient selection and in monitoring the interventional procedures in order to optimize the success rate and minimize the frequency of complications. The current article aims at reviewing the role of multimodality imaging for planning and guiding interventions in several structural heart diseases. PMID- 24215197 TI - Heart transplantation in pediatric cardiomyopathies. AB - Cardiomyopathies represent an uncommon but serious cause of heart disease in the pediatric population and can be categorized as dilated, hypertrophic, restrictive and left ventricular non-compaction. Each of these subtypes has multiple potential genetic etiologies in addition to possible non-genetic causes. Many patients with cardiomyopathies can benefit from transplantation, although there is not insignificant morbidity and mortality for those patients. Outcomes both prior to and following transplantation depend on the underlying etiology, the amount of support needed prior to transplantation and the illness severity of the patient prior to transplantation. Mechanical circulatory support is frequently used to bridge patients to transplantation, and newer technologies are currently in development. PMID- 24215198 TI - Shunt choice in single right ventricle patients: an update. AB - Hypoplastic left heart syndrome, the most common complex congenital heart malformation, is characterized by underdeveloped left-sided heart structures. The Norwood procedure followed by two-staged operations has permitted the extended survival of many of these patients. Survival, however, remains suboptimal with most of the morbidity and mortality occurring during the Norwood procedure hospitalization. The modified Blalock-Taussig shunt has been implicated in contributing to the mortality risk due to decreased systemic diastolic blood pressure and coronary perfusion. Therefore, the right ventricle-to-pulmonary artery shunt was recently reevaluated as a lower-risk source of pulmonary blood flow in the Norwood procedure. The Pediatric Heart Network Single Ventricle Reconstruction trial, sponsored by the NIH National Heart, Lung and Blood Institute, evaluated the two types of shunts during the Norwood procedure. This randomized clinical trial has yielded important insight into the effects of shunt selection on morbidity, mortality, hemodynamics and overall current outcomes for hypoplastic left heart syndrome. PMID- 24215199 TI - Creating the bioartificial myocardium for cardiac repair: challenges and clinical targets. AB - The association of stem cells with tissue-engineered scaffolds constitutes an attractive approach for the repair of myocardial tissue with positive effects to avoid ventricular chamber dilatation, which changes from a natural elliptical to spherical shape in heart failure patients. Biohybrid scaffolds using nanomaterials combined with stem cells emerge as new therapeutic tool for the creation of 'bioartificial myocardium' and 'cardiac wrap bioprostheses' for myocardial regeneration and ventricular support. Biohybrids are created introducing stem cells and self-assembling peptide nanofibers inside a porous elastomeric membrane, forming cell niches. Our studies lead to the creation of semi-degradable 'ventricular support bioprostheses' for adaptative LV and/or RV wrapping, designed with the concept of 'helical myocardial bands'. The goal is to restore LV elliptical shape, and contribute to systolic contraction and diastolic filling (suction mechanism). Cardiac wrapping with ventricular bioprostheses may reduce the risk of heart failure progression and the indication for heart transplantation. PMID- 24215200 TI - Prehypertension and the cardiometabolic syndrome: pathological and clinical consequences. AB - Prehypertension is the category of blood pressure (BP) defined as systolic BP between 120 and 139 mmHg and diastolic BP between 85 and 89 mmHg. Prehypertension is a continuum to hypertension and is emerging as an important risk factor for cardiovascular disease. The definition of the cardiometabolic syndrome is a cluster of several risk factors such as abdominal obesity, prehypertension or hypertension, dyslipidemia and prediabetes. Prevention by lifestyle intervention and also treatment of individual components is recommended, given that most subjects with metabolic syndrome fall into the high-risk category. There are several studies with dietary approaches, which showed that these approaches helped in stopping the progression of hypertension and also improved the metabolic conditions. Several large trials are under way to study several antihypertensive drugs to delay the development of hypertension. Identifying early cardiovascular disease in asymptomatic individuals provides a better guide to the need for individualized preventive therapy than traditional risk factor assessment. PMID- 24215201 TI - Dimensional changes during early healing after a subepithelial connective tissue graft procedure. AB - BACKGROUND: The subepithelial connective tissue graft (CTG) is a popular means to treat gingival recession and augment keratinized tissue. Studies exist that examine long-term outcomes of this procedure; however, changes in tissue dimensions during early healing (0 to 21 days postoperatively) are unknown. The aim of this study is to examine bucco-lingual tissue dimension (gingival tissue thickness [GT]) changes during early CTG healing using a non-invasive technique. METHODS: Thirteen patients who had treatment planned for CTG on a single tooth were recruited for the study. Using a customized acrylic stent, GT was measured preoperatively, at surgery completion, and at 3, 7, 14, and 21 days postoperatively. CTG was performed using an envelope technique. GT changes were analyzed by repeated-measures analysis of variance. RESULTS: All CTG procedures were considered successful with no postoperative complications. GT increased 1.5 mm immediately after surgery (baseline) compared to the preoperative measurement. GT increased on average 96%, 47%, and 2% compared to baseline at days 3, 7, and 14, respectively. Day 3 and day 7 measurements were significantly different from baseline (P <0.001). At day 21, GT decreased 15% compared to baseline, with an average increase of 1.29 mm from preoperative measurements. CONCLUSIONS: The early postoperative healing of CTGs used for root coverage exhibits a significant but transient increase in bucco-lingual tissue dimension. The observed increase in bucco-lingual tissue dimension subsides by the end of the second postoperative week. PMID- 24215202 TI - Crestal bone changes at teeth and implants in periodontally healthy and periodontally compromised patients. A 10-year comparative case-series study. AB - BACKGROUND: Limited data exist on the longitudinal crestal bone changes around teeth compared with implants in partially edentulous patients. This study sought to compare the 10-year radiographic crestal bone changes (bone level [BL]) around teeth and implants in periodontally compromised (PCPs) and periodontally healthy (PHPs) patients. METHODS: A total of 120 patients were evaluated for the radiographic crestal BL around dental implants and adjacent teeth at time of implant crown insertion and at the 10-year follow-up. Sixty patients had a previous history of periodontitis (PCPs), and the remaining 60 were PHPs. In each category (PCP and PHP), two different implant systems were used. The mean BL change at the implant and at the adjacent tooth at the interproximal area was calculated by subtracting the radiographic crestal BL at the time of crown cementation from the radiographic crestal BL at the 10-year follow-up. RESULTS: At 10 years after therapy, the survival rate ranged from 80% to 95% for subgroups for implants, whereas it was 100% for the adjacent teeth. In all eight different patient categories evaluated, teeth demonstrated a significantly more stable radiographic BL compared with adjacent dental implants (teeth BL, 0.44 +/- 0.23 mm; implant BL, 2.28 +/- 0.72 mm; P <0.05). Radiographic BL changes around teeth seemed not to be influenced by the presence or absence of advanced bone loss (>=3 mm) at the adjacent implants. CONCLUSIONS: Natural teeth yielded better long-term results with respect to survival rate and marginal BL changes compared with dental implants. Moreover, these findings also extend to teeth with an initial reduced periodontal attachment level, provided adequate periodontal treatment and maintenance are performed. As a consequence, the decision of tooth extraction attributable to periodontal reasons in favor of a dental implant should be carefully considered in partially edentulous patients. PMID- 24215203 TI - Epigallocatechin-3-gallate attenuates Porphyromonas gingivalis lipopolysaccharide enhanced matrix metalloproteinase-1 production through inhibition of interleukin 6 in gingival fibroblasts. AB - BACKGROUND: Recent studies have shown that epigallocatechin-3-gallate (EGCG), a major constituent of green tea extract, exhibits effects of anti-inflammation and antioxidation on periodontal inflammation. The present in vitro study examines the effect of EGCG on Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) enhanced expression of interleukin (IL)-6 and matrix metalloproteinase (MMP)-1, as well as the activation of nuclear factor-kappa B (NF-kappaB). Furthermore, the role of IL-6 on LPS-enhanced MMP-1 production is evaluated using human gingival fibroblasts (HGFs). METHODS: HGFs were primary cultured from human gingiva specimens. The cytotoxicities of EGCG and LPS were tested by cell viability tests. The cellular mRNA expression of IL-6 was determined by reverse transcription polymerase chain reaction, and the protein expression of MMP-1 and IL-6 was examined by enzyme-linked immunosorbent assay. The cytosol expression and nuclear translocation of NF-kappaB was evaluated by immunocytochemistry followed by confocal laser scanning microscopy. RESULTS: Pg LPS significantly increased MMP-1 production in HGFs, whereas adding EGCG significantly attenuated this enhanced production of MMP-1. LPS treatment also increased the mRNA and protein expression of IL-6 and stimulated NF-kappaB activation in HGFs. However, the addition of EGCG significantly attenuated the IL-6 expression and NF-kappaB activation. Supplemental addition of IL-6 significantly enhanced cellular MMP-1 production, whereas anti-IL-6 antibody inhibited LPS-enhanced MMP-1 production. CONCLUSION: EGCG could attenuate Pg LPS-enhanced production of MMP-1 in HGFs, whereas this attenuation might be due to the inhibition of IL-6 by EGCG. PMID- 24215204 TI - Tooth loss strongly associates with malnutrition in chronic kidney disease. AB - BACKGROUND: In chronic kidney disease (CKD), inadequate nutritional intake, inflammation, and increased oxidative stress have been the major contributing factors in malnutrition pathogenesis. However, there is still a paucity of evidence assessing the magnitude of the effect of tooth loss on malnutrition in CKD populations. The authors hypothesize that among patients with CKD, tooth loss may affect nutritional status, using the National Health and Nutrition Examination Survey 1988 to 1994 (NHANES III). METHODS: Glomerular filtration rate (GFR) was estimated based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio (albuminuria) was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on estimated GFR <60 mL/minute/1.73m(2) and albuminuria >=30 mg/g. The cutoff point for serum albumin was set at 3.7 g/dL. Tooth loss categories were based on the number of missing and replaced teeth. RESULTS: A total of 2,749 patients was included and stratified based on their oral health status. There was a statistically significant correlation between tooth loss and the proportion of patients with low protein and caloric intake (P = 0.02 and 0.01, respectively). Serum albumin reached a frequency peak in the fully edentulous group without dentures (group 4, 19.2%). In the same group, individuals had lower protein (30.1%) and caloric intake (30.2%) (P = 0.01 and 0.02, respectively). Furthermore, logistic regression analysis confirmed the significant role of tooth loss on serum albumin and protein and energy intake in this population even after adjusting for confounding variables. CONCLUSION: Tooth loss independently predicts low energy and protein intake, as well as serum albumin levels, biomarkers of malnutrition in CKD. PMID- 24215205 TI - Bibliometrics study on authorship trends in periodontal literature from 1995 to 2010. AB - BACKGROUND: Biomedical research has grown considerably in the last few decades, and the authorship characteristics of the dental literature as a whole and of its specialty fields has changed significantly. Unfortunately, the bibliometrics of the periodontal literature have not been thoroughly investigated. The aim of this study is to investigate the bibliometrics of periodontal literature, assessing the geographic origin, study design, and topics investigated in periodontal research published from 1995 to 2010. METHODS: Articles published in periodontal journals during 1995 to 2010 were retrieved through hand search. Inclusion/exclusion criteria were applied. The following variables were extrapolated from each article: number of authors, study design, topic investigated, financial support, and geographic origin. The general linear model assessed the influence of independent variables on number of authors per article, and chi(2) test assessed the statistical difference of the variables over years 1995 to 2010. RESULTS: A total of 2,260 articles were reviewed; 2,076 met the inclusion criteria. The number of authors per article increased (P <0.001) from 4.0 (1995) to 5.1 (2010). The proportion of articles published from North America and Europe decreased (P <0.001) from 84.3% (1995) to 58.6% (2010), whereas for Asia and South America the article proportion increased (P <0.001) from 13.8% (1995) to 40% (2010). Research targeting prevention and treatment of periodontal disease is decreasing (P <0.001) in favor of implant-related research. Governmental research funding is increasing (P <0.001). CONCLUSION: Periodontal research significantly changed during the last 15 years. PMID- 24215206 TI - Prevalence and characterization of Salmonella enterica from the feces of cattle, poultry, swine and hedgehogs in Burkina Faso and their comparison to human Salmonella isolates. AB - BACKGROUND: Production and wild animals are major sources of human salmonellosis and animals raised for food also play an important role in transmission of antimicrobial resistant Salmonella strains to humans. Furthermore, in sub-Saharan Africa non-typhoidal Salmonella serotypes are common bloodstream isolates in febrile patients. Yet, little is known about the environmental reservoirs and predominant modes of transmission of these pathogens. The purpose of this study was to discover potential sources and distribution vehicles of Salmonella by isolating strains from apparently healthy slaughtered food animals and wild hedgehogs and by determining the genetic relatedness between the strains and human isolates. For this purpose, 729 feces samples from apparently healthy slaughtered cattle (n = 304), poultry (n = 350), swine (n = 50) and hedgehogs (n = 25) were examined for the presence of Salmonella enterica in Burkina Faso. The isolates were characterized by serotyping, antimicrobial-susceptibility testing, phage typing, and pulsed-field gel electrophoresis (PFGE) with XbaI and BlnI restriction enzymes. RESULTS: Of the 729 feces samples, 383 (53%) contained Salmonella, representing a total of 81 different serotypes. Salmonella was present in 52% of the cattle, 55% of the poultry, 16% of the swine and 96% of the hedgehog feces samples. Antimicrobial resistance was detected in 14% of the isolates. S. Typhimurium isolates from poultry and humans (obtained from a previous study) were multiresistant to the same antimicrobials (ampicillin, chloramphenicol, streptomycin, sulfonamides and trimethoprim), had the same phage type DT 56 and were closely related in PFGE. S. Muenster isolates from hedgehogs had similar PFGE patterns as the domestic animals. CONCLUSIONS: Based on our results it seems that production and wild animals can share the same Salmonella serotypes and potentially transmit some of them to humans. As the humans and animals often live in close vicinity in Africa and the hygiene control of the meat retail chain is defective, high Salmonella carriage rates of the animals can pose a major public health risk in Burkina Faso. This underlines the necessity for a joint and coordinated surveillance and monitoring programs for salmonellosis in Africa. PMID- 24215207 TI - Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review. AB - Elastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior. PMID- 24215208 TI - Lymphedema in a patient with distichiasis. PMID- 24215210 TI - Assessing the cost-effectiveness of finding cases of hepatitis C infection in UK migrant populations and the value of further research. AB - Hepatitis C (HCV) infection can cause cirrhosis, liver cancer and death in the absence of treatment. Many people living in the UK but born overseas are believed to be infected with HCV although many are unlikely to know they are infected. The aim of this study is to assess the potential for a case-finding approach to be cost-effective and to estimate the value of further research. An economic evaluation and value of information analysis was undertaken by developing a model of HCV disease progression and by populating it with evidence from the published literature. They were performed from a UK National Health Services cost perspective, and outcomes were expressed in terms of quality-adjusted life-years (QALYs). The comparator intervention was defined as the background rate of testing (i.e. no intervention). The base case results generated an incremental cost-effectiveness ratio (ICER) of about L23,200 per additional QALY. However, the ICER was shown to be particularly sensitive to HCV seroprevalence, the intervention effect / cost and the probability of treatment uptake. The value of information analysis suggested that approximately L4 million should be spent on further research. This evaluation demonstrates that testing UK migrants for HCV could be cost-effective. However, further research, particularly to refine estimates of the probability of treatment uptake once identified, the utility associated with sustained virological response and the cost of the intervention, would help to increase the robustness of this conclusion. PMID- 24215209 TI - Prognostic impact of baseline serum C-reactive protein in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib. AB - OBJECTIVE: To evaluate the impact of baseline serum C-reactive protein (CRP) level on outcome in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. PATIENTS AND METHODS: We reviewed the charts of patients with mRCC who started sunitinib as a first targeted treatment between 2005 and 2012 in three hospitals in Belgium and France. Collected data included known prognostic factors for mRCC, anatomical location of metastatic sites, response rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 200 eligible patients were identified by retrospective chart review. The median PFS and OS were 12 and 20 months, respectively. We observed a clear impact of baseline CRP levels on outcome: the median PFS was 25 months in the group with baseline CRP <=5 mg/L and 8 months in the group with baseline CRP >5 mg/L (hazard ratio [HR] 2.48, 95% CI 1.74-3.59). The median OS in each group was 50 vs 12 months, respectively (HR 3.17, 2.20-4.68). In the group with baseline CRP <=5 mg/L, 61% of patients experienced a partial response compared with 32% of patients in the group with baseline CRP >5 mg/L (difference = 29%, 95% CI 15-42). When adding baseline CRP (with a log transformation) to the six variables of the International Metastatic RCC Database Consortium (IMDC) model in a multivariable Cox regression model, baseline CRP was independently associated with poor PFS (HR for each doubling in CRP level: 1.14, 95% CI 1.03-1.26; P = 0.01) and OS (HR: 1.29, 95% CI 1.16-1.43; P < 0.001). Adding baseline CRP to the model increased the c-statistic of PFS at 5 years from 0.63 (0.59-0.68) to 0.69 (0.65-0.73), and the c-statistic of OS at 5 years from 0.65 (0.60-0.69) to 0.70 (0.66-0.74). Patients with elevated baseline CRP levels had a poor prognosis independent of the IMDC risk group, whereas patients with a low baseline CRP in the IMDC favourable risk group had a very good outcome. CONCLUSION: Baseline serum CRP level is a strong independent variable linked with RR, PFS and OS in patients with mRCC treated with sunitinib. PMID- 24215211 TI - Infarct characteristics by CMR identifies substrate for monomorphic VT in post-MI patients with relatively preserved systolic function and ns-VT. AB - BACKGROUND: The extent of peri-infarct zone (PIZ) by contrast-enhanced cardiac magnetic resonance (ce-CMR) has been related to inducibility of ventricular arrhythmia in patients with ischemic cardiomyopathy. However, this relationship has not been established in postmyocardial infarction (post-MI) patients with relatively reserved left ventricular (LV) systolic function yet. In this study, we investigated myocardial scar size and characteristics and its relationship with ventricular arrhythmia inducibility in patients with relatively preserved LV systolic function. METHODS: This study enrolled 28 post-MI patients with a left ventricular ejection fraction between 40% and 50% and nonsustained ventricular tachycardia who underwent programmed ventricular stimulation (PVS) for risk stratification. Cine and gadolinium-enhanced cardiac magnetic resonance imaging was performed before PVS. A computer-assisted algorithm quantified the total scar (TS) size and divided it into the dense scar (DS) and the PIZ based on signal intensity thresholds (>6 standard deviations [SDs] and 2 to 6 SDs above remote normal myocardium, respectively). Scar measurements were determined and compared among noninducible (n = 19) and inducible patients (n = 9). RESULTS: The groups had similar baseline clinical characteristics. The LV masses, volumes, and ejection fractions did not differ significantly between the groups. For the inducible versus noninducible patients, DS percent was similar (3.11 +/- 1.02% vs 3.44 +/- 0.79%, P = NS). PIZ percent (28.02 +/- 7.49% vs 19.86 +/- 7.82%, P = 0.01) and TS percent (31.14 +/- 7.96% vs 23.31 +/- 8.21%, P = 0.02) were associated with inducibility of monomorphic VT. Multivariate analysis demonstrated that PIZ percent (P = 0.021, OR [odds ratio] 1.18, 95% CI [confidence interval] 1.03-1.35), and TS percent (P = 0.03, OR 1.15, 95% CI 1.01 1.30) were independent predictors of inducibility. CONCLUSIONS: Higher PIZ percent and TS percent were correlated with increased ventricular inducibility. These data support the hypothesis that ce-CMR may be used to identify the substrate for ventricular arrhythmia in this cohort. PMID- 24215212 TI - Histological features associated with occult lymph node metastasis in FIGO clinical stage I, grade I endometrioid carcinoma. AB - AIMS: Lymph node involvement affects prognosis/treatment in endometrial carcinoma patients. We assessed various histological features associated with nodal metastasis in patients with grade I, stage I endometrial endometrioid carcinoma (EEC). METHODS AND RESULTS: Eighteen stage I EECs with occult positive lymph nodes and 36 controls were assessed for depth of myoinvasion; microcystic, elongated and fragmented (MELF) pattern of myometrial invasion; lymphovascular invasion (LVI); and epithelial metaplasia. Nodal metastases were subclassified as isolated tumour cells (ITCs; <=0.2 mm), micrometastasis (>0.2 mm and <2 mm), or macrometastasis (>=2 mm). Node-positive cases had significantly higher rates of LVI (P < 0.001) and MELF invasion (P = 0.003) on univariate analysis. Only LVI was associated significantly with nodal metastasis on multivariate analysis (P = 0.002). Tumours with MELF invasion demonstrated reduced E-cadherin expression. Macrometastases were identified in seven cases (39%) with or without micrometastasis/ITCs. Eight (44%) contained only ITCs. Eleven (61%) had histiocyte-like nodal metastases. Biopsy material from four of six (67%) and five of 17 (29%) cases with and without nodal metastasis showed detached eosinophilic tumour cell buds. Of the former, three were associated with histiocyte-like nodal metastases - a feature absent in biopsies without tumour budding. CONCLUSIONS: Lymph nodes from grade I EEC exhibiting cellular budding or LVI should be examined for occult metastases, especially in the form of histiocyte-like cells. PMID- 24215213 TI - Atypical mature bone in the otosclerotic otic capsule as the differentiated zone of an invasive osseous neoplasm. AB - CONCLUSION: A large proportion of the mature otic capsule bone in cases of otosclerosis lies in plaques in direct contiguity with active otosclerosis and, because it shows significant structural defects, it should be regarded as part of the otosclerotic process. These appearances support our previously described suggestion that otosclerosis is an invasive osseous neoplasm, the mature atypical bone representing differentiation of earlier-formed invasive neoplastic osseous tissue. OBJECTIVES: We sought structural features in differentiated bone within the otic capsules of cases of otosclerosis that might indicate a relation to the underlying disease process. METHODS: Fifty temporal bones from 42 adult patients with otosclerosis were processed into stained histological sections and the appearance of the otic capsule was compared with that of the same tissue, processed in the same way, in 10 cases that did not show otosclerosis. RESULTS: In the cochlear otic capsules of otosclerotic temporal bones, when traced back along the otosclerotic plaque from the invasive front, atypical shapes and arrangements of osteons were seen, often with otospongiosis (severe dilatation of multiple Volkmann's canals), culminating in larger differentiated osteons with irregularities in structure. In the medial region of the otosclerotic cochlear otic capsule, at a similar position to that where giant normal osteons are present in the normal temporal bone, differentiated, giant abnormal osteons were seen. In the otosclerotic vestibular otic capsule there were changes similar to those of the otosclerotic cochlea (apart from the giant osteons) and many osteons composed of clusters of atypical osteoblast-like cells around highly atypical Volkmann's canals. PMID- 24215214 TI - Phonological outcome of laryngeal framework surgery by different anesthesia protocols: a single-surgeon experience. AB - CONCLUSION: Similar to combined arytenoid adduction and medialization laryngoplasty (i.e. combined surgery) under local anesthesia, general anesthesia by intubation or by the laryngeal mask airway (LMA) method significantly improves phonological outcome. Thus, laryngeal framework surgery under general anesthesia is a promising surgical approach for selected patients with unilateral vocal cord paralysis (UVCP). OBJECTIVE: The advantages of laryngeal framework surgery under local anesthesia have been described, but no studies exist concerning the difference in phonological outcome of laryngeal framework surgery performed under general anesthesia. To add new information, we retrospectively investigated the phonological outcome of the combined surgery performed under three different anesthesia protocols. METHODS: Thirty-nine consecutive patients with severe UVCP underwent the combined surgery under three anesthesia protocols performed by a single surgeon: (1) under general anesthesia by intubation, (2) under general anesthesia using LMA, and (3) under local anesthesia. RESULTS: Under all anesthesia protocols, the vocal cords of most patients could be positioned such that the best vocal outcome could be expected. Statistical analyses demonstrated improved maximum phonation time and mean airflow rate, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale in all patients, regardless of their anesthesia protocol. Furthermore, of the three protocols, local anesthesia had the shortest operation time. PMID- 24215215 TI - Antimicrobial prophylaxis in tonsillectomy: the efficacy of preoperative single dose oral administration of azithromycin in preventing surgical site infection. AB - CONCLUSION: The results indicate that oral administration of azithromycin (AZM) is equivalent to intravenous administration of cefazolin (CEZ) for preventing surgical site infection (SSI) in patients undergoing tonsillectomy, and should be used as cost-effective antimicrobial prophylaxis. OBJECTIVE: Staphylococcus aureus, Streptococcus spp., and pharyngeal anaerobes have been described as major pathogens causing SSI in transpharyngeal operations such as tonsillectomy. The purpose of this study was to explore whether administration of AZM, an oral antimicrobial agent, might be equivalent to intravenous administration of a first generation cefem antimicrobial agent for preventing SSI in patients undergoing tonsillectomy. METHODS: Patients undergoing tonsillectomy were divided into an AZM-treated group and a CEZ-treated group, for intergroup comparison of responses. AZM was administered once orally, 2 days before the operation, whereas patients in the CEZ-treated group received CEZ intravenously 30 min before the operation, 4 h postoperatively, and then twice daily for 3 consecutive days beginning the day after the operation. RESULTS: There were no significant intergroup differences in mean duration of hospitalization after the operation, incidence of postoperative hemorrhage, postoperative analgesic effect, or hematologic/blood biochemical findings. The incidence of postoperative fever was significantly lower in the AZM-treated group. Diarrhea occurred as an adverse drug reaction in the AZM-treated group, but no clinically significant adverse reactions were noted. PMID- 24215216 TI - Correlation between maximum phonetically balanced word recognition score and pure tone auditory threshold in elder presbycusis patients over 80 years old. AB - CONCLUSIONS: The maximum phonetically balanced word recognition score (PBmax) showed poor correlation with pure-tone thresholds in presbycusis patients older than 80 years. OBJECTIVES: To study the characteristics of monosyllable recognition in presbycusis patients older than 80 years of age. METHODS: Thirty presbycusis patients older than 80 years were included as the test group (group 80+). Another 30 patients aged 60-80 years were selected as the control group (group 80-) . PBmax was tested by Mandarin monosyllable recognition test materials with the signal level at 30 dB above the averaged thresholds of 0.5, 1, 2, and 4 kHz (4FA) or the maximum comfortable level. The PBmax values of the test group and control group were compared with each other and the correlation between PBmax and predicted maximum speech recognition scores based on 4FA (PBmax predict) were statistically analyzed. RESULTS: Under the optimal test conditions, the averaged PBmax was (77.3 +/- 16.7) % for group 80- and (52.0 +/- 25.4) % for group 80+ (p < 0.001). The PBmax of group 80- was significantly correlated with PBmax-predict (Spearman correlation = 0.715, p < 0.001). The score for group 80+ was less statistically correlated with PBmax-predict (Spearman correlation = 0.572, p = 0.001). PMID- 24215217 TI - Effectiveness of transcutaneous electrical stimulation for chronic tinnitus. AB - CONCLUSION: Based on the Tinnitus Handicap Inventory (THI) and visual analog scale (VAS) scores, transcutaneous electrical stimulation (TENS) can provide relief from tinnitus. Response to electrical stimulation was best seen in patients with low-frequency tinnitus and with mild hearing loss. OBJECTIVE: TENS is known to alleviate symptoms of tinnitus. However, study of the effectiveness of TENS for tinnitus has produced variable results, and it is still unclear what kind of patients with tinnitus would respond best to TENS. Here, we assessed the effects of TENS on the perception of tinnitus using the THI and VAS questionnaires. METHODS: A total of 65 patients with tinnitus were divided into two groups: 45 patients received TENS and 20 patients received placebo (sham stimulation) twice a week over 4 weeks. THI and VAS scores were assessed before and after electrical stimulation. We also evaluated the effects of TENS on the degree of initial hearing loss and tinnitus frequency. RESULTS: Twenty-eight of 45 patients (62.2%) revealed subjective improvement in tinnitus with TENS. TENS was more effective in patients with low-frequency tinnitus or with mild hearing loss. Symptomatic improvement in the electrical stimulation group was achieved for 1 month in most patients. PMID- 24215218 TI - Gentamicin-induced structural damage of human and artificial (biomimetic) otoconia. AB - CONCLUSIONS: Gentamicin causes irreversible structural damage of human and artificial otoconia by progressive dissolution of calcite. The inner architecture of otoconia is strongly affected by degradation scenarios during gentamicin exposure. Artificial otoconia can be used as a model system mimicking the chemical attacks for detailed investigations. OBJECTIVES: To investigate the chemical interactions of gentamicin with natural calcite and human and artificial otoconia under in vivo conditions. METHODS: Pure calcite crystals and artificial and human otoconia were exposed to gentamicin injection solutions at various concentrations. Morphological changes were observed in time steps by the use of environmental scanning electron microscopy (ESEM). RESULTS: Dissolution of pure calcite crystals results in the formation of well oriented nanoshoots indicating an irreversible chemical reaction with gentamicin. Human and artificial otoconia reveal irreversible structural changes of their surface areas as well as of their inner structure, resulting in characteristic changes at different gentamicin concentrations. Minor changes are first observed by surface alterations and dissolution of calcite in the belly region. Major changes result in further reduction of the belly area reaching the center of symmetry. Finally, a complete dissolution of the branches takes place. Artificial otoconia provide detailed insight into surface alterations. PMID- 24215219 TI - Ocular vestibular evoked myogenic potentials induced by bone-conducted vibration in patients with unilateral inner ear disease. AB - CONCLUSION: Patients with vestibular neuritis (VN) with complete canal paresis (CP) showed a higher rate of abnormal ocular vestibular evoked myogenic potential (oVEMP) than those with partial CP. From these results, it is speculated that the superior vestibular nerve function mainly affects oVEMP. Significant correlation was found between the grades of the hearing outcome and oVEMP in sudden sensorineural hearing loss (SSHL). OBJECTIVE: We attempted to correlate the results of oVEMP with the results of cervical VEMP (cVEMP), results of subjective visual vertical (SVV), and clinical course in patients with various vestibular disorders. METHODS: Twenty-two patients with VN, 65 with SSHL, and 22 with Meniere's disease (MD), were enrolled in this study. We compared the results of oVEMP with those of cVEMP, SVV, and the caloric test. Furthermore, the oVEMP results were compared with the initial hearing threshold, presence of vertigo, and hearing recovery in the patients with SSHL. RESULTS: The patients with VN with complete CP showed a higher rate of abnormal oVEMP than those with partial CP. In the patients with SSHL, the hearing recovery rate was lower in the patients with abnormal oVEMP than in those with normal oVEMP. PMID- 24215220 TI - Ten-year changes in the prevalence of overweight, obesity and central obesity among the Chinese adults in urban Shanghai, 1998-2007 - comparison of two cross sectional surveys. AB - BACKGROUND: In China, obesity is expected to increase rapidly in both urban and rural areas. However, there have been no comprehensive reports on secular trends in obesity prevalence among Chinese adults in urban Shanghai, which is the largest city in southern China. METHODS: In 1998-2001 and again in 2007-2008, two independent population-based cross-sectional surveys were conducted in Shanghai to investigate the prevalence of metabolic disorders. These surveys obtained height, waist circumference (WC), and weight measurements for Chinese adults aged between 20 and 74 years who lived in urban communities. From the 1998-2001 survey, 4,894 participants (2,081 men and 2,813 women, mean age: 48.9 years) were recruited, and 4,395 participants (1,599 men and 2,796 women, mean age: 49.8 years) were recruited from the 2007-2008 survey. Using the World Health Organization criteria, overweight was defined as 25 kg/m2 <= BMI < 30 kg/m2 and obesity as BMI >= 30 kg/m2. Central obesity was defined as WC >= 90 cm in men or >=85 cm in women. The differences in prevalence of obesity, central obesity and overweight between the two surveys were tested using multivariable logistic regression analyses. RESULTS: Compared to the 1998-2001 survey, in the 2007-2008 survey the BMI distribution for men and the WC distribution for both genders is shifted significantly to the right along the x-axis (all p < 0.001). Over the ten years, the prevalence of combined overweight and obesity increased 24% (from 31.5% to 39.1%, p < 0.001) in men, but decreased 8% (from 27.3% to 25.0%; p < 0.01) in women. The prevalence of central obesity increased 40% in men (from 19.5% to 27.3%; p < 0.01), but the increase was not significant in women (15.0% to 17.1%; p = 0.051). In the total population, only central obesity showed a significant change between the populations in the two surveys, increasing 29% (from 17.3% to 22.4%; p < 0.001). CONCLUSIONS: Over this 10 year period, central obesity increased significantly in the Shanghai adult population. However, the prevalence of combined overweight and obesity was significantly increased in men but not in women. PMID- 24215221 TI - Electroretinogram and visual-evoked potential assessment of retinal and central visual function in a rat ocular hypertension model of glaucoma. AB - PURPOSE/AIM: The aim of the study was to investigate the long-term functional changes that may occur in the retina and visual cortex in a rat ocular hypertension (OHT) model of glaucoma, used in our lab for treatment studies, using electroretinogram (ERG) and visual-evoked potential (VEP) cortical recordings in order to test the hypothesis that experimental glaucoma has differential retinal and central effects. MATERIALS AND METHODS: Experimental glaucoma was induced unilaterally in Dark Agouti rats using hypertonic saline injection into the episcleral veins. After 3, 8, 16 and 26 weeks, ERGs and VEPs were recorded under scotopic conditions using brief full-field white flashes (10 MUcd s m(-2) to 10.4 cd s m(-2)) and under photopic conditions using a rod adapting background and white light flashes (0.13-10.4 cd s m(-2)). RESULTS: At 16 and 26 weeks after OHT induction, there was a significant reduction in the amplitudes of the a- (50% and 30% of unoperated eye values, respectively) and b waves (55% and 40%, respectively) of the scotopic ERG and the b-waves of the photopic ERG (55% and 45%, respectively) in the glaucomatous eyes. However, no significant changes in the VEPs simultaneously recorded over the visual cortex were seen at any of the time points. CONCLUSIONS: The reductions in ERG amplitudes suggest that this model of glaucoma not only causes retinal ganglion cell (RGC) degeneration but also degeneration of the outer retinal cells, and this was confirmed by histology showing a reduction in the outer retinal layers in the glaucomatous eyes. Cortical VEPs did not show detrimental effects suggesting that the retinal damage in this model was not extensive enough to be detected with the VEP methods used or that there could be central compensation in this model of glaucoma. PMID- 24215222 TI - The role of perceived peer prejudice and teacher discrimination on adolescent substance use: a social determinants approach. AB - Although Black adolescents have reported a lower prevalence of substance use relative to non-Hispanic Whites, Black youth are disproportionately affected by adverse social outcomes. Social scientists have highlighted that using a framework that includes perceived peer prejudice and teacher discrimination as social determinants of adolescent risk behaviors is essential to fully understanding substance use behaviors in adolescents. However, this area of research remains underdeveloped. This study examined whether and to what extent perceived peer prejudice and teacher discrimination affect binge drinking and marijuana use by Black (n = 514) and non-Hispanic White (n = 2,818) adolescents using data from the National Longitudinal Study of Adolescent Health, Wave 2, Public Use dataset. Findings suggest that peer prejudice increased the risk of substance use in non-Hispanic White youth only, whereas experiences of teacher discrimination increased the risk of substance use in both Black and non-Hispanic White youth. The study's limitations are noted, and implications for future research are discussed. PMID- 24215223 TI - The social norms and beliefs of teenage male electronic cigarette use. AB - Electronic cigarettes (e-cigarettes) are novel, battery-operated inhalation devices that provide warm, vaporized nicotine, and often propylene glycol, to users without the inclusion of tobacco smoke. Because men, in general, are more likely to use cigarettes and illicit drugs than women, a qualitative study was undertaken to investigate the beliefs and perceived social norms regarding this issue among 47 teenage boys who self-identified themselves as current e-cigarette smokers. The majority of respondents reported that they used e-cigarettes because of expeditious consumption and concealment. Furthermore, the most common places respondents self-reported using e-cigarettes were everywhere, in school bathrooms, at home, and in school staircases. Interestingly, respondents stated that e-cigarettes are popular because they are accessible, healthier than tobacco cigarettes, and more aesthetically pleasing. Because of the growing popularity and uncertainty regarding the social and physical consequences of e-cigarettes, this study shows a need for additional research discovery. PMID- 24215224 TI - Acculturation stress and drinking problems among urban heavy drinking Latinos in the Northeast. AB - This study investigates the relationship between the level of acculturation and acculturation stress and the extent to which each predicts problems related to drinking. Hispanics who met criteria for hazardous drinking completed measures of acculturation, acculturation stress, and drinking problems. Sequential multiple regression was used to determine whether the levels of self-reported acculturation stress predicted concurrent alcohol problems after controlling for the predictive value of the acculturation level. Acculturation stress accounted for a significant variance in drinking problems, while adjusting for acculturation, income, and education. Choosing to drink in response to acculturation stress should be an intervention target with Hispanic heavy drinkers. PMID- 24215225 TI - Evaluating a bilingual voluntary community-based healthcare organization. AB - The current study compared traditional recovery homes for individuals with substance use disorders with homes that had been modified to feature culturally congruent communication styles. Findings indicated significant increases in employment income, with the size of the change significantly greater in the culturally modified houses. Significant decreases in alcohol use over time were also found, with larger decreases over time in the traditional recovery homes. Use of prescribed medications and days using drugs significantly decreased over time, but not differentially for those in the two types of recovery homes. The implications of these findings are discussed. PMID- 24215226 TI - Travellers accessing addiction services in Ireland (2007 to 2010): analysis of routine surveillance data. AB - By accessing addiction treatment services recorded in routine national drug treatment data, the characteristics of Irish Travellers were analyzed to understand their needs and develop policies to tackle issues faced by this community. The number of Traveller cases accessing services increased by 163% between 2007 and 2010. Alcohol and opiates were the most common problem substances reported. Traveller women reported high rates of problem opiate use and risky injecting behaviors, contrary to the perception that problem substance use is a predominantly male issue. This presents a challenge to services to provide targeted, effective services to Travellers with problem substance use. PMID- 24215227 TI - Culturally adapted motivational interviewing for Latino heavy drinkers: results from a randomized clinical trial. AB - A randomized clinical trial of culturally adapted and unadapted motivational interviewing to reduce drinking and related problems among heavy drinking Latinos assessed 57 participants at baseline and at 2 (86% retention) and 6 months (84% retention) after treatment. Significant decreases across both treatments were found in heavy drinking days per month and drinking consequences (p < .001), with greater reductions for drinking consequences for culturally adapted motivational interviewing at 2 months (p = .009) and continuing reductions in culturally adapted motivational interviewing at 6 months. Findings provide preliminary support for the value of cultural adaptation to enhance the efficacy of motivational interviewing with Latino heavy drinkers. PMID- 24215228 TI - Patient navigation to promote smoking cessation among low-income primary care patients: a pilot randomized controlled trial. AB - We conducted a pilot randomized controlled trial to determine the feasibility and acceptability of a patient navigation intervention. Forty-seven smokers from one safety-net hospital were randomized to either a control group, in which they received a smoking cessation brochure and a list of smoking cessation resources, or a navigation group, in which they received the smoking cessation brochure, a list of smoking cessation resources, and patient navigation. Follow-up data were obtained for 33 participants. Nine (47.4%) of 19 of navigation group participants had engaged in smoking cessation treatment by 3 months versus 6 (42.9%) of 14 control group participants (chi-square p = ns). Patient navigation to promote engagement in smoking cessation treatment was feasible and acceptable to participants. PMID- 24215230 TI - Pathogenic immune mechanisms at the neuromuscular synapse: the role of specific antibody-binding epitopes in myasthenia gravis. AB - Autoantibodies against three different postsynaptic antigens and one presynaptic antigen at the neuromuscular junction are known to cause myasthenic syndromes. The mechanisms by which these antibodies cause muscle weakness vary from antigenic modulation and complement-mediated membrane damage to inhibition of endogenous ligand binding and blocking of essential protein-protein interactions. These mechanisms are related to the autoantibody titre, specific epitopes on the target proteins and IgG autoantibody subclass. We here review the role of specific autoantibody-binding epitopes in myasthenia gravis, their possible relevance to the pathophysiology of the disease and potential implications of epitope mapping knowledge for new therapeutic strategies. PMID- 24215231 TI - Balancing the costs of carbon gain and water transport: testing a new theoretical framework for plant functional ecology. AB - A novel framework is presented for the analysis of ecophysiological field measurements and modelling. The hypothesis 'leaves minimise the summed unit costs of transpiration and carboxylation' predicts leaf-internal/ambient CO2 ratios (ci /ca ) and slopes of maximum carboxylation rate (Vcmax ) or leaf nitrogen (Narea ) vs. stomatal conductance. Analysis of data on woody species from contrasting climates (cold-hot, dry-wet) yielded steeper slopes and lower mean ci /ca ratios at the dry or cold sites than at the wet or hot sites. High atmospheric vapour pressure deficit implies low ci /ca in dry climates. High water viscosity (more costly transport) and low photorespiration (less costly photosynthesis) imply low ci /ca in cold climates. Observed site-mean ci /ca shifts are predicted quantitatively for temperature contrasts (by photorespiration plus viscosity effects) and approximately for aridity contrasts. The theory explains the dependency of ci /ca ratios on temperature and vapour pressure deficit, and observed relationships of leaf delta(13) C and Narea to aridity. PMID- 24215232 TI - Experimental biomechanical assessment of plate stabilizers for treatment of pectus excavatum. AB - The paper discusses results of experimental research involving new generation of plate stabilizers used for the treatment of deformation of the front chest wall. Previous clinical monitoring revealed instances of minimal rotation, which caused destabilization of the anastomosis and pain in patients. In order to prevent this, transverse stabilizing plates were introduced to the structure of the stabilizer. The new structure of stabilizers was tested using two specially prepared research posts: 1 - which enables fastening of the plate stabilizers to a platform simulating human ribs, 2 - using a pig chest, to which plates were fastened according to the stabilization conditions in the stabilizer-chest structure. The tests recorded displacement values in selected areas of the plates in response to applied loading forces. PMID- 24215234 TI - A two-step synthesis of alpha-keto vinyl carbinols from ketones. AB - Conjugate addition of lithium enolates onto terminal alkynyl- and allenyl sulfoxides furnishes the corresponding allylic sulfoxides. The latter readily undergo a Mislow-Braverman-Evans rearrangement to yield the targeted alpha-keto vinyl carbinols. This two-step procedure does not require purification of the intermediates and constitutes the shortest approach to alpha-keto vinyl carbinols. PMID- 24215235 TI - Use of anthropometry--its importance and critical use in the assessment of growth. PMID- 24215236 TI - Molecular mobility of amorphous S-flurbiprofen: a dielectric relaxation spectroscopy approach. AB - Amorphous S-flurbiprofen was obtained by the melt quench/cooling method. Dielectric measurements performed in the isochronal mode, conventional and temperature modulated differential scanning calorimetry (TMDSC) studies showed a glass transition, recrystallization, and melting. The different parameters characterizing the complex molecular dynamics of amorphous S-flurbiprofen that can have influence on crystallization and stability were comprehensively characterized by dielectric relaxation spectroscopy experiments (isothermal mode) covering a wide temperature (183 to 408 K) and frequency range (10(-1) to 10(6) Hz): width of the alpha-relaxation (betaKWW), temperature dependence of alpha relaxation times (taualpha), fragility index (m), relation of the alpha relaxation with the beta-secondary relaxation, and the breakdown of the Debye Stokes-Einstein (DSE) relationship between the structural relaxation time and dc conductivity (sigmadc) at deep undercooling close to Tg. The beta-relaxation, observed in the glassy as well as in the supercooled state was identified as the genuine Johari-Goldstein process, attributed to localized motions and regarded as the precursor of the alpha-relaxation as suggested in the coupling model. A separation of about 6 decades between the alpha- and beta-relaxation was observed at Tg; this decoupling decreased on increasing temperature, and both processes merged at Talphabeta = 295 K. The temperature dependence of the alpha-relaxation time, taualpha, was described by two Vogel-Fulcher-Tammann-Hesse equations, which intercept at a crossover temperature, TB = 290 K, close to the splitting temperature between the alpha- and beta-relaxation. From the low temperature VFTH equation, a Tg(DRS) = 265.2 was estimated (at taualpha =100 s) in good agreement with the calorimetric value (Tg,onset,TMDSC = 265.6 K), and a fragility or steepness index m = 113 was calculated allowing to classify S-flurbiprofen as a fragile glass former. The alpha-relaxation spectra were found to be characterized by a relatively large degree of nonexponentiality (betaKWW = 0.52). A breakdown of the DSE log10 sigmadc - log10 tau relation was observed revealing an enhancement of translational ionic motions in comparison with the orientational molecular motions as the glass transition temperature Tg is approached from above. PMID- 24215233 TI - Aging related changes of retina and optic nerve of Uromastyx aegyptia and Falco tinnunculus. AB - Aging is a biological phenomenon that involves gradual degradation of the structure and function of the retina and optic nerve. To our knowledge, little is known about the aging-related ocular cell loss in avian (Falco tinnunculus) and reptilian species (Uromastyx aegyptia). A selected 90 animals of pup, middle, and old age U. aegyptia (reptilian) and F. tinnunculus (avian) were used. The retinae and optic nerves were investigated by light and transmission electron microscopy (TEM) and assessments of neurotransmitters, antioxidant enzymes (catalase, superoxide dismustase and glutathione s transferase), caspase-3 and -7, malonadialdhyde, and DNA fragmentation. Light and TEM observations of the senile specimens revealed apparent deterioration of retinal cell layers, especially the pigmented epithelium and photoreceptor outer segments. Their inclusions of melanin were replaced by lipofuscins. Also, vacuolar degeneration and demyelination of the optic nerve axons were detected. Concomitantly, there was a marked increase of oxidative stress involved reduction of neurotransmitters and antioxidant enzymes and an increase of lipid peroxidation, caspase-3 and -7, subG0/G1 apoptosis, and P53. We conclude that aging showed an inverse relationship with the neurotransmitters and antioxidant enzymes and a linear relationship of caspases, malondialdhyde, DNA apoptosis, and P53 markers of cell death. These markers reflected the retinal cytological alterations and lipofuscin accumulation within inner segments. PMID- 24215237 TI - Discovery and characterization of a novel dihydroisoxazole class of alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators. AB - Positive allosteric modulators ("potentiators") of alpha-amino-3-hydroxy-5-methyl 4-isoxazolepropionic acid (AMPA) receptors (AMPAR) enhance excitatory neurotransmission and may improve the cognitive deficits associated with various neurological disorders. The dihydroisoxazole (DHI) series of AMPAR potentiators described herein originated from the identification of 7 by a high-throughput functional activity screen using mouse embryonic stem (mES) cell-derived neuronal precursors. Subsequent structure-based drug design using X-ray crystal structures of the ligand-binding domain of human GluA2 led to the discovery of both PF 04725379 (11), which in tritiated form became a novel ligand for characterizing the binding affinities of subsequent AMPAR potentiators in rat brain homogenate, and PF-04701475 (8a), a prototype used to explore AMPAR-mediated pharmacology in vivo. Lead series optimization provided 16a, a functionally potent compound lacking the potentially bioactivatable aniline within 8a, but retaining desirable in vitro ADME properties. PMID- 24215238 TI - Alcohol use and HIV disease management: the impact of individual and partner level alcohol use among HIV-positive men who have sex with men. AB - Alcohol use among HIV-positive (HIV+) individuals is associated with decreased adherence to antiretroviral therapy (ART) and consequently poorer HIV treatment outcomes. This study examined the independent association of individual and partner-level alcohol use with HIV disease management among men who have sex with men (MSM) in primary partnerships. In total, 356 HIV+ MSM and their male primary partners completed a baseline visit for a longitudinal study examining the role of couple-level factors in HIV treatment. The Alcohol Use Disorders Identification Test (AUDIT) was administered to assess the individual and the partner-level alcohol use. Primary outcome variables included self-reported ART adherence, ART adherence self-efficacy, and HIV viral load. Results demonstrated that abstainers, compared to hazardous drinkers, had higher self-efficacy to integrate and persevere in HIV treatment and a lower odds of having a detectable viral load. Participants with a partner-abstainer, versus a partner-hazardous drinker, had less self-efficacy to persevere in HIV treatment, a lower odds of 100% three-day adherence and a higher viral load. Together, these findings suggest that assessment and treatment of both the patient's and the patient's primary partner's pattern of alcohol consumption is warranted when attempting to optimize HIV care among MSM. PMID- 24215239 TI - Ionic and tautomeric composition of cytosine in aqueous solution: resonance and non-resonance Raman spectroscopy study. AB - A complex experimental and theoretical study of the structural composition of cytosine in water was performed. Raman and resonance Raman spectra of cytosine in acidic, neutral, and alkaline water solutions (pH = 3, 7, and 10, respectively) were recorded at excitation wavelengths of 514, 266, 218, and 200 nm. The temperature dependence of the frequencies and intensities of the resonance Raman bands was obtained in the temperature interval of 4-80 degrees C. To interpret the experimental Raman and resonance Raman spectra and to determine the structural composition of the water solution of cytosine, the spectra of cytosine and its cation, anion, oxoimine, and hydroxoamine forms were calculated at the B3LYP/6-311++G(d,p) level using the SCRF method. The electronic spectra and geometric parameters of the cytosine and its molecular forms in the excited electronic states close to the excitation wavelengths of the resonance Raman spectra were calculated using the DFT method. The cation exists in the acidic solution together with cytosine and its oxoimine and hydroxoamine tautomeric forms. Cytosine with a small amount of anion dominates in the alkaline medium. The structural composition of the water solution of cytosine is confirmed by the results of quantum-mechanical calculations of the intensity distribution in the resonance Raman spectra. PMID- 24215240 TI - The management of antimicrobial-resistant enteric fever. PMID- 24215241 TI - Recent advances in experimental models of osteomyelitis. PMID- 24215243 TI - Sofosbuvir (GS-7977), a pan-genotype, direct-acting antiviral for hepatitis C virus infection. AB - Given the global importance of chronic hepatitis C virus infection as a major health burden, there is still a need for treatment options that are more efficient, safer, simpler, more convenient and preferably interferon-free. Sofosbuvir (GS-7977; formerly PSI-7977) is a direct-acting antiviral agent that has met many of these attributes. This novel nucleotide analogue has demonstrated a consistently potent antiviral activity across several hepatitis C virus genotypes, and has been found to be safe and well tolerated when administered alone or with ribavarin +/- pegylated interferon. The clinical data evaluating the safety, tolerability and antiviral activity of sofosbuvir in various treatment regimens are presented in this article. Sofosbuvir is a major breakthrough in the care of HCV infection, making it possible that thousands of HCV infected patients around the world achieve cures, and preventing HCV associated morbidity and mortality. PMID- 24215244 TI - Is there a role for statins in fungal infections? AB - It has been hypothesized that statins, HMG-CoA reductase inhibitors, may be used to treat fungal infections. Here we review data on antifungal properties of statins, effects on the host inflammatory response as well as available clinical evidence. We conclude that: statins exhibit antifungal properties in vitro although at supraphysiological concentrations; statins appear to have anti inflammatory effects on host cells in vitro; statins have effects on fungal physiology beyond direct growth inhibition; clinical studies are scarce (n = 5), and their design is retrospective and observational, which is associated with a high risk of bias. Given the limited evidence for a beneficial effect of statins in fungal infection, randomized and controlled trials are highly warranted in this field. PMID- 24215246 TI - Exposure to bisphenol A affects lipid metabolism in Drosophila melanogaster. AB - Exposure to bisphenol A (BPA) in rodents was shown to induce obesity, yet the mechanism by which BPA might induce obesity is still unclear. We employed the genetically tractable model organism, Drosophila melanogaster, to test the effects of raising them on food containing various concentrations of BPA. Of note, raising males on food containing BPA were susceptible to starvation, possibly by inhibiting their ability to perform lipolysis during starvation, leading to significantly increased lipid content after 24 hr of fasting. Furthermore, feeding males with BPA significantly inhibited the expression of insulin-like peptides. From these results, we conclude that BPA may inhibit lipid recruitment during starvation in Drosophila. PMID- 24215248 TI - All for one and one for all. PMID- 24215249 TI - Determinants of the effect of existential behavioral therapy for bereaved partners: a qualitative study. AB - BACKGROUND: Informal caregivers of palliative patients took part in existential behavioral therapy (EBT), a group intervention comprising mindfulness exercises to reduce psychological distress and improve quality of life. OBJECTIVES: This study examined what the participants perceived as helpful to cope with their loss during the first year of bereavement, particularly with regard to the EBT intervention. DESIGN: Sixteen problem-centered, semi-structured interviews were evaluated with content analysis. RESULTS: Two main categories were found: social support and self-regulation. Social support includes sense of belonging as well as emotional, cognitive, and practical help experienced from others. Mindfulness and acceptance, a clear focus on the positive, and orientation toward the future were helpful strategies of self-regulation; these were also part of the EBT intervention. Mindfulness was understood as permitting emotions and acceptance of one's inner processes, even if they were not pleasant, and was found to be helpful to stop ruminative thinking. CONCLUSIONS: The categories considered as being helpful parallel core elements of EBT and recent grief theories. The intervention was found to be supportive and met the needs of the participants. The interviewees appreciated the continuity of EBT support from palliative care into bereavement. PMID- 24215250 TI - Is it appropriate to withdraw antibiotics in terminal patients with cancer with infection? AB - BACKGROUND: Antibiotic administration is frequent in terminal patients with cancer, yet the effects on survival are still under debate. OBJECTIVE: The aim of this study was to examine the status of infection and the benefit/burden of antibiotic administration on the survival of terminal patients with cancer with infection. DESIGN: A prospective observational study. SETTING/SUBJECTS: We studied 799 patients with terminal cancer who were admitted to a palliative care unit in Taiwan between January 2008 and the end of April 2010. Survival was calculated from the first day of admission to the day of death in the palliative care unit or under home care. MEASUREMENTS: A specially designed assessment tool was used daily to evaluate clinical conditions. Afterwards, it was analyzed at different time points in a weekly team meeting. Multivariate Cox proportional hazard analyses were used to examine the benefit/burden of antibiotic administration on survival. RESULTS: Four hundred fifty-five patients were diagnosed as having at least one episode of infection after first admission. A total of 295 of the 378 (78.0%) with infection received antibiotic treatment upon admission. Multivariate Cox proportional hazard analyses showed that antibiotic administration was related to improved survival for patients who were still alive 1 week after admission (hazard ratio: 0.66, 95% confidence interfal [CI]: 0.46 0.95). However, antibiotics would be a hazard to patients' survival if used in the time 2 days prior to death (hazard ratio: 1.54, 95% CI: 1.22-1.94). CONCLUSIONS: The results suggest that with good communication between patients, families, and medical staff, withdrawal of antibiotics should be considered if signs of death appear, in order to avoid unnecessary risks. The possible benefit of prolonged survival should be in line with the goal of care, and also take into account preparing the patient for a dignified death. PMID- 24215251 TI - Evaluation of quality of life in complete locked-in syndrome patients. AB - BACKGROUND: There are few studies where quality of life (QOL) and contributive factors are assessed in locked-in syndrome (LIS) patients with complete physical and functional disability and dependence on caregivers. OBJECTIVE: The study's objective was evaluation of QOL in LIS patients. DESIGN: We have compared QOL in LIS patients with QOL in healthy controls (control group). SETTING/SUBJECTS: We have included 19 LIS patients, most of them with vascular etiologies or terminal course of ALS, and 20 healthy controls comparable with LIS patients for age; none of them was in a caregiving position. MEASUREMENTS: Administered to patients and controls were the McGill Quality of Life Single Item Scale (MQOL-SIS) Part A; Short Form survey (SF-36), Mental Component Summary (MCS) and Physical Component Summary (PCS); Beck Depression Inventory-II (BDI-II); and Toronto Alexithymia Scale (TAS). RESULTS: Mean MQOL-SIS and MCS SF-36 were not significantly different between the LIS group and healthy controls. PCS SF-36 score was significantly higher in controls. There were no significant differences between the two groups for TAS scores. Frequency of depressive symptoms was significantly higher in LIS patients than in controls. CONCLUSION: In our study, QOL in LIS patients was not significantly altered compared to control subjects in MQOL-SIS and in the MCS SF-36 scale; these results match previous studies published in the literature. Several factors may have an impact on QOL in LIS patients, such as family support and patient-computer communication devices; these may have contributed to improve QOL in LIS patients in this study. PMID- 24215252 TI - The increase of vasomotor tone avoids the ability of the dynamic preload indicators to estimate fluid responsiveness. AB - BACKGROUND: The use of vasoconstrictor can affect the dynamic indices to predict fluid responsiveness. We investigate the effects of an increase of vascular tone on dynamic variables of fluid responsiveness in a rabbit model of hemorrhage, and to examine the ability of the arterial pressure surrogates dynamic indices to track systolic volume variation (SVV) during hypovolemia under increased vasomotor tone. METHODS: Eighteen anesthetized and mechanically ventilated rabbits were studied during normovolemia (BL) and after blood progressive removal (15 mL/kg, BW). Other two sets of data were obtained during PHE infusion with normovolemia (BL + PHE) and during hypovolemia (BW + PHE). We measured central venous and left ventricular (LV) pressures and infra diaphragmatic aortic blood flow (AoF) and pressure. Pulse pressure variation (PPV), systolic pressure variation (SPV) and SVV were estimated manually by the variation of beat-to-beat PP, SP and SV, respectively. We also calculated PPVapnea as 100 * (PPmax PPmin)/PP during apnea. The vasomotor tone was estimated by total peripheral resistance (TPR = mean aortic pressure/mean AoF), dynamic arterial elastance (Eadyn = PPV/SVV) and arterial compliance (C = SV/PP). We assessed LV preload by LV end-diastolic pressure (LVEDP). We compared the trending abilities between SVV and pressure surrogate indices using four-quadrant plots and polar plots. RESULTS: Baseline PPV, SPV, PPVapnea, and SVV increased significantly during hemorrhage, with a decrease of AoF (P < 0.05). PHE induced significant TPR and Eadyn increase and C decrease in bled animals, and a further decrease in AoF with a significant decrease of all dynamic indices. There was a significant correlation between SVV and PPV, PPVapnea and SPV in normal vasomotor tone (r2 >= 0.5). The concordance rate was 91%, 95% and 76% between SVV and PPV, PPVapnea and SPV, respectively, in accordance with the polar plot analysis. During PHE infusion, there was no correlation between SVV and its surrogates, and both four quadrant plot and polar plot showed poor trending. CONCLUSION: In this animal model of hemorrhage and increased vasomotor tone induced by phenylephrine the ability of dynamic indices to predict fluid responsiveness seems to be impaired, masking the true fluid loss. Moreover, the arterial pressure surrogates have not the reliable trending ability against SVV. PMID- 24215253 TI - Evaluating the efficacy of subcutaneous C1-esterase inhibitor administration for use in rat models of inflammatory diseases. AB - CONTEXT: C1-esterase inhibitor (C1-inh) therapy is currently administered to patients with C1-inh deficiency through intravenous injections. The possibility of subcutaneous administration is currently being explored since this would alleviate need for hospitalization and increase mobility and well-being of patients. Recently, it was observed in pigs that C1-inh indeed can effectively be applied by subcutaneous injection. For studies on the effectiveness of C1-inh therapy for other indications than acquired and hereditary angioedema, rats are commonly used as model animal. For rats, however, subcutaneous C1-inh administration has never been investigated. OBJECTIVE: To evaluate the efficacy of subcutaneous C1-inh administration in rats. MATERIALS AND METHODS: Three boli of 100 U/kg human plasma-derived C1-inh were administered to Wistar rats on three consecutive days through subcutaneous injection or intravenous injection. Blood samples were collected from the tail veins 3, 4.5 or 6 h after C1-inh administration for measurement of C1-inh plasma levels. Antigen and activity levels of C1-inh of each plasma sample were determined by means of a specific ELISA. RESULTS: For both C1-inh antigen and C1-inh activity, 21- to 119-fold higher plasma levels were measured after intravenous administration compared with subcutaneous administration. Subcutaneous administration also resulted in C1-inh plasma levels that were less stable and with decreased relative activity. CONCLUSION: These combined results indicate that in rats, subcutaneous injections in the present formulation are not effective as alternative administration route for C1-inh. PMID- 24215254 TI - Cross-national patterns of intergenerational continuities in childbearing in developed countries. AB - Earlier work has shown that the association between the fertility of parents and the fertility of children has become stronger over time in some societies. This article updates and broadens the geographic coverage to assess the magnitude of intergenerational continuities in childbearing in developed and middle-income societies using data for 46 populations from 28 developed countries drawn from a number of recent large-scale survey programs. Robust positive intergenerational fertility correlations are found across these countries into the most recent period, and although there is no indication that the strength of the relationship is declining, the increasing trend does not appear to be continuing. PMID- 24215255 TI - Health, retirement, and migration from metro counties: evidence from the health and retirement study. AB - Event history analyses and difference-in-proportions tests are used to analyze 1994-2003 data from the Health and Retirement Survey. For young-old metropolitan adults who had never retired, self-rated health (SRH) was unrelated to the odds of becoming a migrant, but for those who had retired, better SRH raised the odds. Neither SRH nor its interwave change was related to the risk of a nonmetro or metro destination. Metro-metro and metro-nonmetro migrants were indistinguishable in their recalled reasons for migration. The implications of the findings for theory and future research are discussed. PMID- 24215256 TI - Income gains and very low-weight birth among low-income black mothers in California. AB - We test the hypothesis suggested in the literature that an acute income gain in the form of the earned income tax credit reduces the odds of a very low-weight birth among low-income non-Hispanic black mothers. We apply ecological time series and supplemental individual-level logistic regression methods to monthly birth data from California between 1989 and 1997. Contrary to our hypothesis, the odds of very low-weight birth increases above its expected value two months after mothers typically receive the credit. We discuss our findings in relation to the epidemiologic literature concerned with ambient events during pregnancy and recommend further investigation. PMID- 24215257 TI - Understanding how family socioeconomic status mediates the maternal intelligence child cognitive outcomes relationship: a moderated mediation analysis. AB - In a model of moderated mediation using matched data from the 1979 National Longitudinal Survey of Youth and the 1979 National Longitudinal Survey of Youth, Children and Young Adults, I test (1) whether family socioeconomic status (SES) mediates the maternal intelligence-child cognitive outcomes relationship and (2) the extent to which this mediating impact is dependent on the level of maternal intelligence. Results reveal that the mediating impact of SES on the maternal intelligence-child cognitive outcomes relationship varies as a function of the level of maternal intelligence. The positive effect of higher SES on children's academic ability decreases as the cognitive ability of mothers increases, such that children in low IQ households benefit most from higher SES, while children in high IQ households benefit somewhat less. PMID- 24215258 TI - Influenza as a proportion of pneumonia mortality: United States, 1959-2009. AB - As causes of death, influenza and pneumonia are typically analyzed together. We quantify influenza's contribution to the combined pneumonia and influenza mortality time series for the United States, 1959-2009. A key statistic is I/(P + I), the proportion of pneumonia and influenza mortality accounted for by influenza. Year-to-year, I/(P + I) is highly variable and shows long-term decline. Extreme values of I/(P + I) are associated with extreme P + I death rates and vice versa, but I/(P + I) is a weak predictor of P + I mortality overall. Prominence of influenza in the medical news is associated with high I/(P + I). Influenza and pneumonia should be analyzed as a combined cause. PMID- 24215259 TI - Are stepparents always evil? Parental death, remarriage, and child survival in demographically saturated Krummhorn (1720-1859) and expanding Quebec (1670-1750). AB - Parental death precipitates a cascade of events leading to more or less detrimental exposures, from the sudden and dramatic interruption of parental care to cohabitation with stepparents and siblings in a recomposed family. This article compares the effect of early parental loss on child survival in the past in the Krummhorn region of East Frisia (Germany) and among the French Canadian settlers of the Saint Lawrence Valley (Quebec, Canada). The Krummhorn region was characterized by a saturated habitat, while the opportunities for establishing a new family were virtually unlimited for the French Canadian settlers. Early parental loss had quite different consequences in these dissimilar environments. Event history analyses with time-varying specification of family structure are used on a sample of 7,077 boys and 6,906 girls born between 1720 and 1859 in the Krummhorn region and 31,490 boys and 33,109 girls whose parents married between 1670 and 1750 in Quebec. Results indicate that in both populations, parental loss is associated with increased infant and child mortality. Maternal loss has a universal and consistent effect for both sexes, while the impact of paternal loss is less easy to establish and interpret. On the other hand, the effect of the remarriage of the surviving spouse is population-specific: the mother's remarriage has no effect in Krummhorn, while it is beneficial in Quebec. In contrast, the father's remarriage in Krummhorn dramatically reduces the survival chances of the children born from his former marriage, while such an effect is not seen for Quebec. These population-specific effects appear to be driven by the availability of resources and call into question the universality of the "Cinderella" effect. PMID- 24215260 TI - The reproductive transition in an indigenous population of northern Argentina. AB - Latin America has been registering a fast decrease in fertility rates since the mid-twentieth century. This change can be linked to the modernization process these populations have been undergoing. However, research with Latin American indigenous populations, which are undergoing relatively similar lifestyle changes, shows very different trends in fertility. The aim of this study was to analyze fertility patterns in the indigenous Toba community of Cacique Sombrero Negro, which is experiencing a rapid process of economic and social Westernization. Fertility patterns were analyzed between 1981 and 1999, the period for which the most accurate records were found. Results showed an overall increase in fertility rates and changes in the age of peak fertility across time periods. It is hypothesized that the lifestyle transition this population is experiencing leads to better access to resources that, in the absence of contraception, allow for a higher number of offspring. Nevertheless, this higher resource availability would be differential, affecting mostly the fertility of younger mothers. PMID- 24215262 TI - Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence. AB - Neuroinflammatory signaling pathways in the central nervous system are of current interest as potential pharmacotherapy targets for alcohol dependence. In this study, we examined the ability of ibudilast, a non-selective phosphodiesterase inhibitor, to reduce alcohol drinking and relapse in alcohol-preferring P rats, high-alcohol drinking HAD1 rats, and in mice made dependent on alcohol through cycles of alcohol vapor exposure. When administered twice daily, ibudilast reduced alcohol drinking in rats by approximately 50% and reduced drinking by alcohol-dependent mice at doses which had no effect in non-dependent mice. These findings support the viability of ibudilast as a possible treatment for alcohol dependence. PMID- 24215263 TI - A subset of Rosai-Dorfman disease cases show increased IgG4-positive plasma cells: another red herring or a true association with IgG4-related disease? PMID- 24215265 TI - Overcoming fixed mindsets: the role of affect. AB - When there is an established strategy to solve a problem, we often approach the problem with a mindset that makes us blind for more efficient solutions. We examined the role of affect in overcoming such blinding effects of mindsets. As positive affect is known to broaden and negative affect to narrow thought-action repertoires, we speculated that positive affect facilitates and negative affect impedes the overcoming of a current mindset. To induce a mindset, participants initially solved 60 similar problems which were only solvable using the same complex strategy. After a short break in which positive or negative affect was induced, participants continued to work on the problems. Critically, there now was an additional simple way to solve the problems. Participants experiencing positive affect were more likely to detect the simple solution than participants experiencing negative affect. These findings reveal that affect modulates how much we are constrained by current mindsets. PMID- 24215264 TI - Impact of human papillomavirus-related genital diseases on quality of life and psychosocial wellbeing: results of an observational, health-related quality of life study in the UK. AB - BACKGROUND: Data on the psychosocial burden of human papillomavirus (HPV)-related diseases other than cervical cancer are scarce. The objectives of this study were to measure and compare the psychosocial burden and the impact on health-related quality of life (HRQoL) of HPV-related lower genital tract diseases and genital warts (GW) using several generic and disease-specific instruments. METHODS: Overall, 842 individuals with normal cervical cytology (n = 241), borderline nuclear abnormalities and/or mild dyskaryosis (n = 23), cervical intraepithelial neoplasia (CIN)1 (n = 84), CIN2/3 (n = 203), vulval intraepithelial neoplasia (VIN)2/3 (n = 43), GW (n = 186) and a history of GW (non-current) (n = 62) were included. The generic European Quality of Life Index Version 5D (EQ-5D) questionnaire was completed by patients with GW and VIN2/3. Sexual functioning was evaluated using the Change in Sexual Functioning Questionnaire (CSFQ). Psychosocial impact was measured in women using the HPV Impact Profile (HIP) questionnaire. HRQoL was assessed using a GW-specific questionnaire, the Cuestionario Especifico en Condilomas Acuminados (CECA) (completed by patients with GW and history of GW). For each instrument, scores were compared between groups using the Student's t-test. In addition, utility loss due to GW and VIN2/3 was evaluated by comparing mean EQ-5D scores weighted by age and sex with the UK general population normal values. RESULTS: A significant psychosocial impact was found in women diagnosed with HPV-related genital diseases, particularly in those with GW. The health state of younger adults with GW was significantly impaired compared with UK normal values (mean EQ-5D index score 0.86 vs 0.94, p < 0.001 for 18-24-year-olds; 0.87 vs 0.93, p = 0.030 for 25-34-year-olds). VIN2/3 was found to have a significant negative impact on sexual functioning, and women with VIN2/3 had a highly impaired health state compared with women in the UK general population (weighted mean EQ-5D index score 0.72 vs 0.89, p < 0.001; weighted mean Visual Analogue Scale score 62 vs 85, p < 0.001). CONCLUSIONS: HPV-related lower genital tract lesions and GW significantly impair psychosocial wellbeing and HRQoL. The psychosocial aspects of HPV-related diseases need to be considered when evaluating the potential benefit of HPV vaccination. PMID- 24215266 TI - Chronic cocaine effects in retinal metabolism and electrophysiology: treatment with topiramate. AB - PURPOSE: Cocaine abuse is a major public health problem with multiple-related complications. Indeed, cocaine can affect almost every organ of the human body, but little is known about its effects on the visual system. The main purpose of this work was to study if topiramate was able to reverse changes in retinal metabolism and retinal function induced by chronic cocaine exposure in adult rats. MATERIALS AND METHODS: Sixteen Wistar rats were treated with a daily oral dose of cocaine during 36 days. Sixteen rats receiving NaCl 0.9% served as controls. Eight control and eight cocaine animals were administered topiramate from day 18 to day 36 of the experiment. Malondialdehyde (MDA), glutathione (GSH) and glutamate content, as well as glutathione peroxidase (GPx) activity in retina tissue homogenates were determined. Retinal function was assessed by electroretinogram (ERG). RESULTS: Glutamate concentration was increased in the retinas of cocaine-treated rats. No changes in oxidative stress parameters were observed in the retinas of cocaine-treated rats when compared with the control ones. Cocaine induced a decrease in the a-wave and b-wave ERG amplitude. The administration of topiramate reversed cocaine-induced increase in glutamate concentration and had little effect on a-wave and b-wave ERG amplitude. Topiramate, a drug used during the last decade for the treatment of epileptic seizures, is able to reverse the cocaine-induced alterations observed in retinal glutamate concentration. CONCLUSIONS: We can conclude that retinal glutamate metabolism and function may be affected by exposure to cocaine. We confirm that topiramate, a treatment recently proposed for cocaine dependence, is also able to recover partially cocaine-induced changes in the retina. PMID- 24215267 TI - The effect of anxiety and depression on symptoms attributed to atrial fibrillation. AB - BACKGROUND: Symptoms attributed to atrial fibrillation (AF) are nonspecific, and it remains unclear what influences perception of symptoms. Anxiety or depression may be important in modulating perception of AF symptoms. However, few longitudinal studies have addressed this effect. METHODS: A total of 378 patients with AF completed anxiety and depression severity questionnaires as well as AF symptom and frequency severity questionnaires. Patients were offered treatment strategies including catheter ablation or antiarrhythmic or rate-controlling medications. Patients were followed at 3-month intervals and completed follow-up questionnaires including repeat assessment of anxiety, depression, and AF symptoms. A method of generalized estimating equations was used for longitudinal analyses. RESULTS: Analysis revealed that increased anxiety or depression was associated with increased AF symptom severity (AFSS), after adjusting for potential confounders. In both unadjusted and adjusted follow-up analyses, antiarrhythmic drug therapy or catheter ablation reduced AFSS (P < 0.001). However, none of anxiety severity, depression severity, or the perception of AF frequency severity improved significantly with AF treatment. CONCLUSIONS: Our results extend previous studies demonstrating that anxiety and depression are associated with worsened AFSS. Antiarrhythmic drug therapy or catheter ablation reduces AFSS but does not affect depression and anxiety symptoms. To achieve more comprehensive AF symptom relief, treatment of both AF and psychological comorbidities may be beneficial. PMID- 24215268 TI - Canine antimicrobial peptides are effective against resistant bacteria and yeasts. AB - BACKGROUND: Antimicrobial peptides (AMPs) are small proteins present in most living species and they are involved in the defence against pathogenic organisms. beta-Defensins and cathelicidin are the most frequently studied AMPs in both people and dogs. HYPOTHESIS/OBJECTIVES: Our objectives were to determine the minimal inhibitory concentration and minimal bactericidal concentration of two canine beta-defensins and a cathelicidin against antibiotic-sensitive and antibiotic-resistant bacteria and yeasts using a broth microdilution method. METHODS: The micro-organisms tested were ATCC strains of meticillin-sensitive and meticillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), meticillin-sensitive Staphylococcus pseudintermedius (MSSP), Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Malassezia pachydermatis. Field strains of meticillin-resistant S, pseudintermedius (MRSP, n = 1) and MSSP (n = 11) were also tested. Mann-Whitney U-test and Friedman test were used for statistical analysis. RESULTS: The MSSP and MRSP were more susceptible to canine AMPs than MSSA and MRSA. Malassezia pachydermatis was more sensitive than C. albicans to canine AMPs. The beta-defensin cBD103 was most effective against Staphylococci and P. aeruginosa, while the cathelicidin cCath was the most effective AMP against E. coli. Additionally, cBD103 was the most effective AMP for both yeasts studied, with M. pachydermatis being more susceptible than C. albicans. All AMPs tested exhibited killing within 2 h of exposure. CONCLUSIONS AND CLINICAL IMPORTANCE: We demonstrated that natural canine AMPs are effective against canine-specific pathogens, are equally effective against meticillin resistant or -susceptible strains, and are more effective against M. pachydermatis than against C. albicans organisms. PMID- 24215269 TI - The ecology of sexual conflict: ecologically dependent parallel evolution of male harm and female resistance in Drosophila melanogaster. AB - The prevalence of sexual conflict in nature, along with the potentially stochastic nature of the resulting coevolutionary trajectories, makes it an important driver of phenotypic divergence and speciation that can operate even in the absence of environmental differences. The majority of empirical work investigating sexual conflict's role in population divergence/speciation has therefore been done in uniform environments and any role of ecology has largely been ignored. However, theory suggests that natural selection can constrain phenotypes influenced by sexual conflict. We use replicate populations of Drosophila melanogaster adapted to alternative environments to test how ecology influences the evolution of male effects on female longevity. The extent to which males reduce female longevity, as well as female resistance to such harm, both evolved in association with adaptation to the different environments. Our results demonstrate that ecology plays a central role in shaping patterns of population divergence in traits under sexual conflict. PMID- 24215270 TI - Mock-up in hip arthroplasty pre-operative planning. AB - The correct estimation of stem boundary conditions in hip arthroplasty cannot be performed simply by subtracting the prosthesis volume from the bone volume: the stem implant path needs to be taken into account. Digital mock-up is a technique commonly applied in the automotive field which can be used for this aim. Given a certain femur, a stem, and an implantation path, the volume of the removed bone stock can be evaluated, as well as the final contact area between the bone and the stem, and, section by section, the residual cortical bone thickness. The technique proved to be useful: if the stem implant path is not considered, the removed bone stock volume can be underestimated up to 6%, while the contact area extension can be overestimated up to 28%. On the whole, a new methodology has been set up and tested, which can be usefully employed to accurately establish stem boundary conditions in the pre-operative planning stage, and in order to perform a reliable structural stress analysis. The methodology implemented here by experienced researchers can be made available to surgeons, setting up an apposite software suite. PMID- 24215271 TI - Time perspective and perceived risk as related to mammography screening. AB - The present study explored the relation of time perspective to perceived risk for breast cancer and mammography screening. Women free from breast cancer (N = 194), eligible for mammography screening in terms of age, completed the Zimbardo Time Perspective Inventory (Zimbardo & Boyd, 1999) and measures of perceived risk, attitude toward performing mammography screening, intention to get a mammogram, and mammography screening behavior. Hierarchical multiple regression analysis revealed that perceived risk of breast cancer (beta= .18, p < .01) and intention to be screened (beta = .35, p < .01) were significantly associated with mammography screening, after controlling for the effects of sociodemographic (e.g., age, education, and economic level) and health-related variables (e.g., family history of breast cancer and previous benign breast disease). Path analyses including the main psychological variables indicated that perceived risk was indirectly related to intention via attitude (beta = .17, p < .01), and to mammography screening through attitude and intention (beta = .06, p < .01). Attitude was indirectly related to mammography screening via intention (beta = .20, p < .01). Also, a significant indirect association was observed between future orientation and mammography screening, via perceived risk (beta = .10, p < .01). Theoretical implications of study findings and suggestions for future research on use of mammography are presented. PMID- 24215272 TI - Consideration of abortion in pregnancy: demographic characteristics, mental health, and protective factors. AB - This study examined demographic characteristics, available resources, and mental health outcomes of women who did and did not consider abortion in pregnancy. Using data collected between 1998 and 2000 from 2,937 mothers recruited for the Fragile Families and Child Well-Being Study, this study examined whether women who did and did not consider abortion differed in terms of sociodemographic characteristics and resources at the birth of their children and mental health outcomes when their children were one year old. This study further examined protective factors associated with low parenting stress at one year postpartum, despite initial abortion consideration. Compared to women who did not consider abortion, women who did consider abortion tended to be younger, have less education and lower income, and report higher levels of substance use, higher perceived support, and lower received support. A subset of women who had higher education, more income, and lower substance use reported lower parenting stress at year one despite abortion consideration in pregnancy. Promotion of education and employment assistance may be particularly important among women experiencing unplanned pregnancies as these services may contribute to lower parenting stress and improved child outcomes. PMID- 24215274 TI - Psychopathological symptoms and locus of control in women with low-risk pregnancies. AB - This study investigated the role of locus of control in the development of psychopathological symptoms during pregnancy and postpartum in women with low risk pregnancies. Pregnant women participated during the first trimester of pregnancy (n = 285), third trimester (n = 122), and in the postpartum (n = 116). Participants were assessed for locus of control (first and third trimesters) and psychopathological symptoms (first and third trimesters and postpartum). Sociodemographic and pregnancy variables (previous childbirth, previous miscarriage, and whether the pregnancy was planned) were also assessed. Significant differences were observed in the development of somatization and obsessive-compulsive symptoms during pregnancy and postpartum. Both increased in the third trimester and decreased after delivery. Previous births, planned pregnancy, having a job, and increasing age were protective variables. As pregnancy progressed, locus of control was significantly externalized. In the first trimester, significant differences were found for locus of control (internal vs. external) among almost all the psychopathological symptoms, but in the third trimester, significant differences were only found in obsessive compulsiveness and interpersonal sensitivity. In two trimesters, internal locus of control was a protective health variable. Regression analysis showed that external locus of control was related only to phobic anxiety in the third trimester. Adoption of a bio-psycho-social model, such as internal locus of control, may increase personal resources in pregnant women. PMID- 24215273 TI - Fear of violent consequences and condom use among women attending an STD clinic. AB - Intimate partner violence (IPV) has been associated with risk for HIV infection. This cross-sectional study tested the hypothesis that fear of violent consequences when negotiating condom use mediated the relation between IPV and condom use. Participants (n = 478) were recruited between March 1, 2004 and June 30, 2006 from a public clinic that treats sexually transmitted diseases in upstate New York as part of a randomized controlled trial. They completed an audio, computer-assisted, self-administered questionnaire with items on risky sexual behavior, intimate relationships, and related covariates and confounding variables. Seventeen percent of the sample reported IPV in the past three months. Recent IPV was associated with fear of violent consequences to requests for condom use, and such fear was associated with inconsistent condom use. Women who reported IPV also reported greater difficulties in negotiating safer sex behaviors with their abusers. So fear of violent consequences appeared to hinder their ability to protect themselves against HIV infection. The results were consistent with fear of violent consequences mediating the relationship between IPV and condom use. Health care providers involved in HIV prevention and sexual risk reduction interventions need to address IPV and, more specifically, fear of IPV when negotiating safer sex as part of their services for providing more comprehensive care to the women they serve. PMID- 24215275 TI - Information needs, seeking behaviors, and support among low-income expectant women. AB - Previous studies have consistently found associations between low income and infant health outcomes. Moreover, although health information-seeking is a maternal behavior related to improved health outcomes, little is known about the health information-seeking behaviors and information needs of low-income pregnant women. The purpose of the current investigation was to examine the information needs, information-seeking behaviors, and perceived informational support of low income pregnant women. Accordingly, the study recruited 63 expectant women enrolled in a subsidized prenatal care program in Milwaukee, Wisconsin, during two time periods: March-May 2011 and October-December 2011. Results indicated that participants relied heavily upon interpersonal sources of information, especially family and the father of the baby; rarely used the Internet for health related information; and desired information beyond infant and maternal health, such as finding jobs and accessing community/government resources. Participants who used family members as primary sources of information also had significantly increased levels of perceived informational support and reduced uncertainty about pregnancy. Our findings have implications for the dissemination of pregnancy related health information among low-income expectant women. PMID- 24215276 TI - Association between females' perceptions of college aerobic class motivational climates and their responses. AB - The aim of this study was to examine the relationship between female college students' perceptions of the motivational climate in their aerobics classes to their adaptive exercise responses. Data were collected from university group exercise classes in spring 2008. The participants (N = 213) responded to a questionnaire measuring perceptions of the climate (i.e., caring, task-, and ego involving), correlates of intrinsic motivation (i.e., interest/enjoyment, perceived competence, effort/importance, and tension/pressure), commitment to exercise, and reasons for exercising. Canonical correlation analyses revealed that participants who perceived a predominately caring, task-involving climate reported higher interest/enjoyment, perceived competence, effort/importance, and commitment to exercise, as well as lower tension/pressure. Further, those who perceived a high caring, task-involving, and low ego-involving climate were also more likely to report more health-related reasons for exercise versus appearance focused reasons. Results suggested that important motivational benefits might exist when women perceive caring, task-involving climates in their aerobics class settings. Aerobics class instructors who intentionally create caring, task involving climates may promote more adaptive motivational responses among their female participants. PMID- 24215277 TI - Synthesis and library construction of privileged tetra-substituted Delta5-2 oxopiperazine as beta-turn structure mimetics. AB - In this study, we developed an efficient and practical procedure for the synthesis of tetra-substituted Delta5-2-oxopiperazine that mimics the bioactive beta-turn structural motif of proteins. This synthetic route is robust and modular enough to accommodate four different substituents to obtain a high level of molecular diversity without any deterioration in stereochemical enrichment of the natural and unnatural amino acids. Through the in silico studies, including a distance calculation of side chains and a conformational overlapping of our model compound with a native beta-turn structure, we successfully demonstrated the conformational similarity of tetra-substituted Delta5-2-oxopiperazine to the beta turn motif. For the library construction in a high-throughput manner, the fluorous tag technology was adopted with the use of a solution-phase parallel synthesis platform. A 140-membered pilot library of tetra-substituted Delta5-2 oxopiperazines was achieved with an average purity of 90% without further purification. PMID- 24215278 TI - Internet-delivered acceptance and values-based exposure treatment for fibromyalgia: a pilot study. AB - BACKGROUND: Acceptance and commitment therapy (ACT) is a promising treatment option for fibromyalgia (FM). Studies have shown that many cognitive behavioral protocols can be transferred to the Internet with sustained efficacy. However, no study has investigated the effect on an Internet-delivered ACT-based protocol for FM. This study evaluated the efficacy, acceptability, and the health economic effects of an Internet-delivered acceptance and values-based exposure treatment for FM. METHODS: This open pilot trial included 41 self-referred women with a FM diagnosis. The 10-week Internet-delivered treatment included acceptance, mindfulness, work with life-values, and systematic exposure to FM symptoms and FM related situations. Participants also had regular contact with an assigned online therapist. Assessments were made at pretreatment, post-treatment, and 6-month follow-up. RESULTS: The treatment was completed by 70% of the participants. Attrition rates were low, with 98% completing the post-treatment assessment and 90% completing the 6-month follow-up assessment. Multiple imputations were used to replace missing values. Pre- to post-treatment within-group effect sizes were in the moderate to large range (Cohen's d = 0.62-1.56) on measures of FM symptoms and impact, disability, quality of life, depression, anxiety, fatigue, and psychological flexibility. All improvements were maintained at follow-up. Economical analyses revealed significant societal cost reductions that offset the treatment costs within 2 months of treatment completion. CONCLUSIONS: An Internet delivered psychological treatment based on acceptance and exposure principles seems to be an efficacious, acceptable, and cost-effective treatment for FM. Randomized controlled trials are needed to confirm these results. PMID- 24215279 TI - 2-Methylenetetrahydropyrans: efficient partners in the carbonyl ene reaction. AB - The carbonyl ene reaction of 2-methylenetetrahydropyrans provides a rapid, high yielding route for the preparation of beta-hydroxydihydropyrans under mild conditions. This process provides a new entry for the synthesis of 2-substituted tetrahydropyrans and for the direct introduction of oxygen heterocycles into molecular frameworks. PMID- 24215282 TI - Tools for assessing quality of life in epilepsy patients. AB - In this review, we attempt to bring the reader up to date with recent developments in the area of assessment of quality of life (QOL) of patients with epilepsy, in both the research and clinical contexts. We present evidence from recent publications on the major and most commonly used QOL instruments for both adults and children with epilepsy, including both strengths and limitations. We discuss both generic measures and ones that have been developed specifically for use in the epilepsy population. We draw attention to some of the broader issues that render the QOL assessment endeavor a somewhat complex one - in particular, that epilepsy is not a single condition, with a common clinical trajectory; and that QOL measures as currently configured almost universally focus on its negative impacts, largely neglecting the possibility of those affected being able to retain reasonable social adjustment and life satisfaction. Finally, we suggest that further work needs to focus on plugging the current evidence gaps in relation to psychometric and cross-cultural applicability issues; and on the value of QOL instruments in the clinical care setting. We conclude by highlighting a number of issues from the QOL literature that will, in our view, be the focus of increasing research interest in the next few years. PMID- 24215281 TI - Demographic and clinical factors correlating with high levels of psychological distress in HIV-positive women living in Ontario, Canada. AB - The concept of psychological distress includes a range of emotional states with symptoms of depression and anxiety and has yet to be reported in HIV-positive women living in Ontario, Canada, who are known to live with contributing factors. This study aimed to determine the prevalence, severity, and correlates of psychological distress among women accessing HIV care participating in the Ontario HIV Treatment Network Cohort Study using the Kessler Psychological Distress Scale (K10). The K10 is a 10-item, five-level response scale. K10 values range from 10 to 50 with values less than or equal to 19 categorized as not clinically significant, scores between 20 and 24 as moderate levels, 25-29 as high, and 30-50 as very high psychological distress. Correlates of psychological distress were assessed using the Pearson's chi-square test and univariate and multivariate logistic regression analysis. Moderate, high, and very high levels of psychological distress were experienced by 16.9, 10.4, and 15.1% of the 337 women in our cohort, respectively, with 57.6% reporting none. Psychological distress levels greater than 19, correlated with being unemployed (vs. employed/student/retired; AOR = 0.33, 95% CI: 0.13-0.83), living in a household without their child/children (AOR = 2.45, 95% CI: 1.33-4.52), CD4 counts < 200 cells/mm(3) (AOR = 2.07, 95% CI: 0.89-4.80), and to a lesser degree an education of some college or less (vs. completed college or higher; AOR=1.71, 95% CI: 0.99 2.95). Age and ethnicity, a priori variables of interest, did not correlate with psychological distress. Findings suggest that socioeconomic factors which shape the demography of women living with HIV in Ontario, low CD4 counts, and losing the opportunity to care for their child/children has a significant relationship with psychological distress. Approaches to manage psychological distress should address and make considerations for the lived experiences of women since they can act as potential barriers to improving psychological well-being. PMID- 24215280 TI - Nanotechnologies for noninvasive measurement of drug release. AB - A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ~1-100 nm to encapsulate drugs and target them to tumors. The nanoparticle enhances local drug delivery efficiency to the tumors via entrapment in leaky tumor vasculature, molecular targeting to cells expressing cancer biomarkers, and/or magnetic targeting. In addition, the localization can be enhanced using triggered release in tumors via chemical, thermal, or optical signals. In order to optimize these nanoparticle drug delivery strategies, it is important to be able to image where the nanoparticles distribute and how rapidly they release their drug payloads. This Review aims to evaluate the current state of nanotechnology platforms for cancer theranostics (therapeutic and diagnostic particles) that are capable of noninvasive measurement of release kinetics. PMID- 24215283 TI - Myeloid-derived suppressor cells in glioma. AB - Glioblastoma is the most prevalent form of gliomas with high aggressive nature and high recurrence. Despite aggressive therapy, including surgery, chemotherapy and radiotherapy, median patient survival is only about 15 months. Hence, developing novel and efficient therapies seem urgent. Many fields have begun their work in preclinical studies but gained limited success in clinical phases. One of the most notable reasons is tumor-induced immunosuppression. In recent decade, efforts to dissect this immunosuppressive network have been done vastly. In a number of malignancies such as glioma, myeloid-derived suppressor cells (MDSCs) have been shown to infiltrate malignant tissues having critical role in the network. Many studies, most of them on lab models, were conducted to understand how MDSCs take part in immunosuppression. Here, we reviewed MDSC relations with other immunocellular components like T cell and natural killer cell. PMID- 24215284 TI - New targets for deep brain stimulation treatment of Parkinson's disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) has been shown to be an effective treatment for patients with Parkinson's disease. Strong clinical evidence supports the improvement of motor and non-motor complications and quality of life, with some data suggesting that GPi DBS might be less effective than STN DBS. However, neither STN nor GPi stimulation provides a satisfactory control of non dopaminergic symptoms, such as gait and balance impairment and cognitive decline, which are frequent and disabling symptoms in advanced Parkinson's disease patients. Therefore, several efforts have been made to discover alternative and new targets to overcome these current DBS limitations. Among these new targets, the stimulation of the pedunculopontine nucleus has initially appeared encouraging. However, findings from different double-blind trials have mitigated the enthusiasm. A multi-target strategy aimed at improving symptoms with different pathogenetic mechanisms might be a promising approach in the next years. PMID- 24215285 TI - Effect of nitazoxanide on erythrocytes. AB - Nitazoxanide, a drug effective against a variety of pathogens, triggers apoptosis and is thus considered to be employed against malignancy. Similar to nucleated cells, erythrocytes may undergo an apoptosis-like suicidal cell death or eryptosis. Hallmarks of eryptosis include cell shrinkage and phospholipid scrambling of the cell membrane with translocation of phosphatidylserine to the erythrocyte surface. Stimulators of eryptosis include increase in cytosolic Ca(2+) -activity ([Ca(2+) ]i ). The Ca(2+) -sensitivity of eryptosis is increased by ceramide. This study explored whether nitazoxanide triggers eryptosis. [Ca(2+) ]i was estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, ceramide abundance utilizing fluorescent antibodies and haemolysis from haemoglobin release. A 48-hr exposure to nitazoxanide (1-50 MUg/ml) did not significantly modify [Ca(2+) ]i but significantly increased ceramide formation, decreased forward scatter (>=10 MUg/ml), increased the percentage of annexin-V-binding erythrocytes (>=10 MUg/ml) and, at higher concentrations (>=20 MUg/ml), stimulated haemolysis. The stimulation of annexin-V-binding was significantly blunted in the absence of calcium. Nitazoxanide thus stimulates eryptosis, an effect in part due to ceramide formation. PMID- 24215286 TI - New application of indirect fluorescent antibody (IFA) technique using latex particles coupled with verotoxin 2 from Escherichia coli O157:H7 in order to determine colostral antibody titers in immunized dairy cows. AB - A simple and novel assay method for determining colostral and serum against soluble verotxin 2 (VT2) titers by indirect fluorescent antibody (IFA) assay using latex sensitized with VT2 was devised. The latex particles did not auto fluoresce, and non specific reactions disappeared after washing with phosphate buffered saline containing 3 M Nacl. The highest titer measured by neutralizing test was observed at 1 day after delivery. The highest titer for each immunoglobulin class measured by enzyme-linked immunosorbent assay (ELISA) or IFA using latex sensitized with VT2 was also observed at 1 day after delivery. The changes in titer measured by each method showed similar patterns. Furthermore, the titers for IgG antibody were higher than those for IgM or IgA antibodies. Thus, the titers of bovine immune colostral antibody and each immunoglobulin class could be measured by IFA using latex sensitized with VT2. PMID- 24215288 TI - Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-beta-cyclodextrin. AB - The therapeutic potential of acyclovir is limited by the low oral bioavailability owing to its limited aqueous solubility and low permeability. The present study was a systematic investigation on the development and evaluation of inclusion complex using hydroxypropyl-beta-cyclodextrin for the enhancement of oral bioavailability of acyclovir. The inclusion complex of acyclovir was prepared by kneading method using drug: hydroxypropyl-beta-cyclodextrin (1:1 mole). The prepared inclusion complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, NMR spectroscopy and evaluated in vitro by dissolution studies. In vivo bioavailability of acyclovir was compared for inclusion complex and physical mixture in rat model. Phase solubility studies indicate the formation of acyclovir-hydroxypropyl-beta cyclodextrin complex with higher stability constant and linear enhancement in drug solubility with increase in hydroxypropyl-beta-cyclodextrin concentration. Characterization of the prepared formulation confirms the formation of acyclovir hydroxypropyl-beta-cyclodextrin inclusion complex. Dissolution profile of inclusion complex demonstrated rapid and complete release of acyclovir in 30 min with greater dissolution efficiency (90.05 +/- 2.94%). In vivo pharmacokinetic data signify increased rate and extent of acyclovir absorption (relative bioavailability ~160%; p < 0.0001) from inclusion complex, compared to physical mixture. Given the promising results in the in vivo studies, it can be concluded that the inclusion complex of acyclovir could be an effective and promising approach for successful oral therapy of acyclovir in the treatment of herpes viruses. PMID- 24215287 TI - Chlamydia prevalence in the general population: is there a sex difference? a systematic review. AB - BACKGROUND: The focus of Chlamydia trachomatis screening and testing lies more on women than on men. The study aim was to establish by systematic review the prevalence of urogenital Chlamydia trachomatis infection in men and women in the general population. METHODS: Electronic databases and reference lists were searched from 2000 to 2013 using the key words "Chlamydia trachomatis", "population-based study" and "disease prevalence". Reference lists were checked. Studies were included in the analysis if Chlamydia trachomatis prevalence was reported for both men and women in a population-based study. Prevalence rates for men and women were described as well as highest prevalence rate by age and sex. The difference in prevalence between the sexes in each study was calculated. RESULTS: Twenty-five studies met the inclusion criteria and quality assessment for the review. In nine of the twenty-five studies there was a statistically significant sex difference in the chlamydia prevalence. In all nine studies the prevalence of chlamydia was higher in women than in men. The prevalence for women varied from 1.1% to 10.6% and for men from 0.1% to 12.1%. The average chlamydia prevalence is highly variable between countries. The highest prevalence of chlamydia occurred predominantly in younger age groups (< 25 years). The absence of symptoms in population-based urogenital chlamydia infection is common in men and women (mean 88.5% versus 68.3%). CONCLUSIONS: The urogenital chlamydia trachomatis prevalence in the general population is more similar than dissimilar for men and women. A modest sex difference is apparent. The prevalence rates can be used to inform chlamydia screening strategies in general practice. PMID- 24215289 TI - Changes in chemical composition of frozen coated fish products during deep frying. AB - This work evaluates the influence of deep-frying coated fish products on total fat, fatty acid (FA) and amino acid profile, and on the formation of volatile compounds, with special attention on furan and its derivatives due to their potential harmful characteristics. As expected, deep-frying in sunflower oil increased linoleic acid content, but total fat amount increased only by 2% on a dry basis. Eicosapentanoic and docosahexanoic acids were preserved while gamma- and alpha-linoleic acids were oxidised. Deep-frying also induces proteolysis, releasing free AA, and the formation of volatile compounds, particularly aldehydes and ketones arising from polyunsaturated FA. In addition, high quantities of furanic compounds, particularly furan and furfuryl alcohol, are generated during deep-frying coated fish. The breaded crust formed could contribute simultaneously for the low uptake of fat, preservation of long chain n 3 FA, and for the high amounts of furanic compounds formed during the deep-frying process. PMID- 24215290 TI - Well-differentiated neuroendocrine tumour of the breast showing peculiar endovascular spread. PMID- 24215291 TI - Cardiac perforation and lead dislodgement after implantation of a MR-conditional pacing lead: a single-center experience. AB - OBJECTIVE: The purpose of our study was to determine if the rate of lead-related complications was increased with the Medtronic CapSureFix MRITM SureScanTM 5086 MRI pacing lead (5086; Medtronic Inc., Minneapolis, MN, USA) compared to the previous generation of Medtronic CapSureFix NovusTM 5076 pacing lead (5076). BACKGROUND: The 5086 lead is a newly introduced active-fixation pacemaker lead designed to be used conditionally in a magnetic resonance (MR) scanner. This lead has specific design changes compared to the previous generation of 5076 pacing leads. METHODS: This study was a retrospective case control study of 65 consecutive patients implanted with two 5086 leads compared to 92 consecutive control patients implanted with two 5076 leads over a 14-month period at a high volume tertiary care hospital. RESULTS: Pericarditis, pericardial effusion, cardiac tamponade, or death within 30 days of implant were seen in eight patients from the 5086 cohort and two from the 5076 cohort (odds ratio 6.3, 95% confidence interval 1.3-30.8, P = 0.02). Lead dislodgement occurred in four of the 5086 patients and in none of the 5076 patients (P < 0.03). CONCLUSIONS: In a high volume center, the incidence of pericarditis, cardiac perforation, tamponade, death, and lead dislodgement was significantly higher with the MR-conditional Medtronic 5086 lead when compared to the previous generation Medtronic 5076 lead. PMID- 24215292 TI - Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system. AB - VCP/p97 is a hexameric ring-shaped AAA(+) ATPase that participates in various ubiquitin-associated cellular functions. Mis-sense mutations in VCP gene are associated with the pathogenesis of two inherited diseases: inclusion body myopathy associated with Paget's disease of the bone and front-temporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). These pathogenic VCPs have higher affinities for several cofactors, including Npl4, Ufd1 and p47. In Parkin-dependent mitochondrial quality control systems, VCP migrates to damaged mitochondria (e.g., those treated with uncouplers) to aid in the degradation of mitochondrial outer membrane proteins and to eliminate mitochondria. We showed that endogenous Npl4 and p47 also migrate to mitochondria after uncoupler treatment, and Npl4, Ufd1 or p47 silencing causes defective mitochondria clearance after uncoupler treatment. Moreover, pathogenic VCPs show impaired migration to mitochondria, and the exogenous pathogenic VCP expression partially inhibits Npl4 and p47 localization to mitochondria. These results suggest that the increased affinities of pathogenic VCPs for these cofactors cause the impaired movement of pathogenic VCPs. In adult flies, exogenous expression of wild-type VCP, but not pathogenic VCPs, reduces the number of abnormal mitochondria in muscles. Failure of pathogenic VCPs to function on damaged mitochondria may be related to the pathogenesis of IBMPFD and ALS. PMID- 24215293 TI - Anti-VEGF therapy (bevacizumab) for sulfur mustard-induced corneal neovascularization associated with delayed limbal stem cell deficiency in rabbits. AB - PURPOSE: To investigate the involvement of VEGF in corneal neovascularization (CNV) following sulfur mustard (SM) exposure and to test the therapeutic effects of bevacizumab (Avastin) in respect to dose, route of administration and timing. MATERIALS AND METHODS: Topical bevacizumab (6 or 25 mg/ml, *2/day) was applied to rabbit eyes, before or after appearance of NV, following SM vapor exposure, and was compared with subconjunctival injection (25 mg/ml, *2/week) and topical dexamethasone (1%, *4/day). Treatments were given for 3 weeks. VEGF levels were monitored by immunohistochemistry and ELISA assay. Clinical evaluations included slit-lamp examination, impression cytology for diagnosis of Limbal Stem Cell Deficiency (LSCD), pachymetry, measurement of NV length and histology. RESULTS: Corneal NV was developed, as early as 2 weeks after exposure, in 50-70% of the eyes, associated with increased levels of VEGF. Topical bevacizumab treatment with both doses, starting at 4 weeks, reduced vascularization. Subconjunctival injection and topical dexamethasone were more potent. A combined treatment of dexamethasone and bevacizumab improved the anti-angiogenic efficacy, yet, there was no effect on LSCD. Topical bevacizumab treatment starting at 1 week, when VEGF was elevated but before appearance of NV, had no effect. CONCLUSIONS: VEGF was involved in corneal angiogenesis in SM-induced ocular injury. Bevacizumab was beneficial in reducing CNV by both, topical or subconjunctival injection, when given as a symptomatic therapy with or without dexamethasone, however with no effect on SC deficiency. Further studies on the pathological mechanism of SM induced ocular surface disorder may direct towards improved therapy. PMID- 24215294 TI - How does emotional content affect lexical processing? AB - Even single words in isolation can evoke emotional reactions, but the mechanisms by which emotion is involved in automatic lexical processing are unclear. Previous studies using extremely similar materials and methods have yielded apparently incompatible patterns of results. In much previous work, however, words' emotional content is entangled with other non-emotional characteristics such as frequency of occurrence, familiarity and age of acquisition, all of which have potential consequences for lexical processing themselves. In the present study, the authors compare different models of emotion using the British Lexicon Project, a large-scale freely available lexical decision database. After controlling for the potentially confounding effects of non-emotional variables, a variety of statistical approaches revealed that emotional words, whether positive or negative, are processed faster than neutral words. This effect appears to be categorical rather than graded; is not modulated by emotional arousal; and is not limited to words explicitly referring to emotions. The authors suggest that emotional connotations facilitate processing due to the grounding of words' meanings in emotional experience. PMID- 24215295 TI - Simplified production and concentration of lentiviral vectors to achieve high transduction in primary human T cells. AB - BACKGROUND: Lentiviral vectors have emerged as efficient vehicles for transgene delivery in both dividing and non-dividing cells. A number of different modifications in vector design have increased biosafety and transgene expression. However, despite these advances, the transduction of primary human T cells is still challenging and methods to achieve efficient gene transfer are often expensive and time-consuming. RESULTS: Here we present a simple optimised protocol for the generation and transduction of lentivirus in primary human CD45RA+ T cells. We show that generation of high-titre lentivirus with improved primary T cell transduction is dependent upon optimised ultracentrifuge speed during viral concentration. Moreover, we demonstrate that transduction efficiency can be increased with simple modifications to the culturing conditions. Overall, a transduction efficiency of up to 89% in primary human CD45RA+ cells is achievable when these modifications are used in conjunction. CONCLUSION: The optimised protocol described here is easy to implement and should facilitate the production of high-titre lentivirus with superior transduction efficiency in primary human T cells without the need for further purification methods. PMID- 24215296 TI - Transcriptomes of isolated Oryza sativa gametes characterized by deep sequencing: evidence for distinct sex-dependent chromatin and epigenetic states before fertilization. AB - The formation of a zygote by the fusion of egg and sperm involves the two gametic transcriptomes. In flowering plants, the embryo sac embedded within the ovule contains the egg cell, whereas the pollen grain contains two sperm cells inside a supporting vegetative cell. The difficulties of collecting isolated gametes and consequent low recovery of RNA have restricted in-depth analysis of gametic transcriptomes in flowering plants. We isolated living egg cells, sperm cells and pollen vegetative cells from Oryza sativa (rice), and identified transcripts for approximately 36 000 genes by deep sequencing. The three transcriptomes are highly divergent, with about three-quarters of those genes differentially expressed in the different cell types. Distinctive expression profiles were observed for genes involved in chromatin conformation, including an unexpected expression in the sperm cell of genes associated with active chromatin. Furthermore, both the sperm cell and the pollen vegetative cell were deficient in expression of key RNAi components. Differences in gene expression were also observed for genes for hormonal signaling and cell cycle regulation. The egg cell and sperm cell transcriptomes reveal major differences in gene expression to be resolved in the zygote, including pathways affecting chromatin configuration, hormones and cell cycle. The sex-specific differences in the expression of RNAi components suggest that epigenetic silencing in the zygote might act predominantly through female-dependent pathways. More generally, this study provides a detailed gene expression landscape for flowering plant gametes, enabling the identification of specific gametic functions, and their contributions to zygote and seed development. PMID- 24215297 TI - Carrier-mediated magnetoelectric coupling in functionalized graphene. AB - Materials in which magnetic order and electric fields can be coupled are of high fundamental and technological interests. Electrical control of magnetism is not only important for ultralow power consumption applications, but also enables control over intrinsic material properties that may have a major step in new developments in spintronic and magnetoelectric devices. Here we show that the magnetism induced by aryl-radicals covalently functionalized on top of multilayer graphene is sensitive to external electric fields which coupled to the interlayer charge-imbalance yields a strong magnetoelectric coupling. We used first principles simulations, taking into account van der Waals dispersion forces, to show that this effect is thickness-dependent: it increases dramatically to thicker graphene structures reaching magnetoelectric coefficients comparable to perovskite interfaces. The interplay between electric fields and magnetism also leads functionalized graphene layers to a fully polarized spin state (half metallicity). Efficiency nearly to 100% spin-polarization is observed at low electric bias, and the selection of the spin-conducting channel is determined by the field polarization. PMID- 24215298 TI - Tracking young talented swimmers: follow-up of performance and its biomechanical determinant factors. AB - The aim of the study was to follow-up the stability of young talented swimmers' performance and its biomechanical determinant factors (i.e., anthropometrics, kinematics, hydrodynamics and efficiency) during a competitive season. Thirty three (15 boys and 18 girls) young swimmers (overall: 11.81 +/- 0.75 years old and Tanner stages 1-2 by self-evaluation) were evaluated. Performance, anthropometrics, hydrodynamics, kinematics and efficiency variables were assessed at three moments during a competitive season. Performance had a significant improvement (with minimum effect size) and a moderate-very high stability throughout the season. In the anthropometrics domain all variables increased significantly (ranging from without to minimum effect size) between moments and had a moderate-very high stability. Hydrodynamics presented no variations between all moments and had a low-very high stability throughout the season. In the kinematics domain, there were no variations between moment one and three, except for an increase in stroke frequency (without size effect). Speed fluctuation remained constant, with no significant variations. All kinematic variables had a low-very high stability. Efficiency variables did not present variations between moment one and three and had a low-moderate stability. Overall, young swimmers showed a minimum improvement in performance and in anthropometric factors; and a moderate stability of performance and its determinant factors (i.e., anthropometrics, hydrodynamics, kinematics and efficiency) during the competitive season. PMID- 24215299 TI - Sequential targeted delivery of paclitaxel and camptothecin using a cross-linked "nanosponge" network for lung cancer chemotherapy. AB - The applicability of a HVGGSSV peptide targeted "nanosponge" drug delivery system for sequential administration of a microtubule inhibitor (paclitaxel) and topoisomerase I inhibitor (camptothecin) was investigated in a lung cancer model. Schedule-dependent combination treatment with nanoparticle paclitaxel (NP PTX) and camptothecin (NP CPT) was studied in vitro using flow cytometry and confocal imaging to analyze changes in cell cycle, microtubule morphology, apoptosis, and cell proliferation. Results showed significant G2/M phase cell cycle arrest, changes in microtubule dynamics that produced increased apoptotic cell death and decreased proliferation with initial exposure to NP PTX, followed by NP CPT in lung cancer cells. In vivo molecular imaging and TEM studies validated HVGGSSV-NP tumor binding at 24 h and confirmed the presence of Nanogold labeled HVGGSSV-NPs in tumor microvascular endothelial cells. Therapeutic efficacy studies conducted with sequential HVGGSSV targeted NP PTX and NP CPT showed 2-fold greater tumor growth delay in combination versus monotherapy treated groups, and 4-fold greater delay compared to untargeted and systemic drug controls. Analytical HPLC/MS methods were used to quantify drug content in tumor tissues at various time points, with significant paclitaxel and camptothecin levels in tumors 2 days postinjection and continued presence of both drugs up to 23 days postinjection. The efficacy of the NP delivery system in sequential treatments was corroborated in both in vitro and in vivo lung cancer models showing increased G2/M phase arrest and microtubule disruption, resulting in enhanced apoptotic cell death, decreased cell proliferation and vascular density. PMID- 24215300 TI - Universal dark quencher based on "clicked" spectrally distinct azo dyes. AB - The first synthesis of an heterotrifunctional molecular scaffold derived from the popular DABCYL azo dye quencher has been achieved. The sequential derviatization of this trivalent azobenzene derivative with two other nonfluorescent azo dyes (Black Hole Quencher BHQ-1 and BHQ-3) and through effective reactions from the "bioconjugation chemistry" repertoire has led to an universal dark quencher (UDQ). This "clicked" poly azo dye is able to turn off an array of fluorophores covering the UV/NIR (300-750 nm) spectral range. PMID- 24215301 TI - Mineralocorticoid receptor modulators: a patent review (2007 - 2012). AB - INTRODUCTION: Considered for years as a 'renal hormone' leading to the control of renal excretion of minerals (explaining the term 'mineralocorticoid' used to describe this hormone), aldosterone is now recognized as a key factor in several diseases including hypertension, heart failure, arrhythmia, metabolic and kidney diseases, to cite only a few of them. AREAS COVERED: In this review article, the authors aim to cover information provided by patents of the years 2007 through 2012. The rationale of writing this article is to cover the most important patents that can progress the field with new important discoveries. EXPERT OPINION: The recognition of its proinflammatory and fibrogenic effects and the discovery of extrarenal sites of expression of its receptor (the mineralocorticoid receptor or MR) support a broader implication in diseases of MR activation than previously anticipated and the possible novel therapeutic indications of MR antagonists. PMID- 24215302 TI - Are changes in worry associated with treatment response in cognitive behavioral therapy for insomnia? AB - AIM: Little is known about why some patients respond to cognitive behavioral therapy for insomnia, whereas other patients do not. To understand differences in treatment response, there is a dire need to examine processes of change. The purpose was to investigate the long-term association between insomnia-related worry and outcomes following cognitive behavior therapy for insomnia. METHODS: Sixty patients with early insomnia (3-12 months duration) received group cognitive behavioral therapy for insomnia. At pretreatment and at a 1-year follow up, the patients completed questionnaires indexing two domains of insomnia related worry (sleeplessness and health), insomnia severity, anxiety, and depression as well as sleep diaries. RESULTS: Decreases in the two worry domains were associated with improvements in all of the outcomes, except for sleep onset latency (SOL), at a medium to large level. Reductions in insomnia-related worry were associated with improvements in insomnia severity, wake after sleep onset (WASO), total sleep time (TST), and depression, but not in SOL or anxiety. While reductions in worry for sleeplessness were related to improvements in insomnia severity and TST, decreases in worry for health were associated with enhancements in WASO and depression. CONCLUSION: The findings suggest that reductions in insomnia-related worry might be one process route in which cognitive behavioral therapy operates to improve insomnia symptomatology. The results are discussed in relation to theory, clinical implications, and future research. PMID- 24215304 TI - Serum creatinine and albumin decline predict the contraction of nosocomial aspiration pneumonia in patients undergoing hemodialysis. AB - Aspiration pneumonia (AP) is prevalent in older adults and the hemodialysis (HD) population has been getting older. Therefore, it is speculated that increasing number of HD patients would suffer from AP. However, the clinical aspects of AP in HD patients have not been elucidated. Consecutive HD patients with nosocomial AP hospitalized in our university hospital from April 2007 to December 2008 were recruited. Their clinical characteristics, risk factors for contraction, and the fatality of AP and treatment options were described. Nineteen out of 356 hospitalized HD patients had AP and 8 out of 19 AP patients died, indicating the incidence rate and fatality rate were 5.34% and 42.1%, respectively. Multiple regression analysis revealed that the risk factors for contracting AP included age, body mass index, serum creatinine levels (Cre) and the monthly decline rate of Cre. It also revealed that serum albumin (Alb) and basal total cholesterol levels, the decline rate of Alb and Cre levels, and the duration of AP were independent risk factors for fatality. Survivors were most often treated with tube feeding. Both contraction rate and fatality of nosocomial AP were high among HD patients. Both the malnutrition as well as the decline rate for nutrition and muscle volume indicated by falls in Alb and Cre, respectively, had clinical relevance in AP. Maintaining nutritional state by tube feeding and muscle volume seems to be the mainstay for the prevention and the treatment of AP in HD patients. PMID- 24215305 TI - The effect of Mn(II) on the autoinducing growth inhibition factor in Deinococcus radiodurans. AB - Decreases in cell division at the stationary phase in bacterial cultures are often due to the depletion of nutrients and/or accumulation of toxic waste products. Yet, during the stationary phase, the highly radiation-resistant bacterium Deinococcus radiodurans undergoes new rounds of cell division when Mn(II) is added to the medium in a phenomenon known as manganese-induced cell division (MnCD). When cells were cultured in medium without Mn(II)-enrichment, a heat-resistant, proteinase K-resistant factor (or factors) with a molecular mass less than 10 kD accumulated in the spent medium. Inclusion of the concentrated spent medium in fresh medium could inhibit the growth of D. radiodurans significantly, and the degree of inhibition was dose dependent. However, the relative stimulatory effect of MnCD was also dose dependent-the higher the inhibition, the stronger was the MnCD response. Previous studies have shown that nutrients were not limiting and deinococcal cells would continue metabolizing its nutrients at stationary phase. Cells became more sensitive to radiation when nutrients in the medium eventually became depleted. We speculated that D. radiodurans might produce this factor in the medium to control its population density. The reduction in cell population would conserve the nutrients that in turn might enhance the survival of the species. PMID- 24215306 TI - Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study. AB - BACKGROUND: In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes. METHODS: Two studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/MUL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate. RESULTS: The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/MUL showed that, in the total population, the two treatment arms were similar until Week 11-12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p < 0.0001). Similar trends were observed in infants and children <5 years and in individuals >=5 years of age. In infants and children <5 years old who experienced symptomatic malaria episodes, the geometric mean P. falciparum density was lower in the intervention arm than the control arm. This trend was not seen in those individuals aged >=5 years. Over the year, monthly variation in mosquito density and entomological inoculation rate was comparable in both arms, with September peaks in both indices. CONCLUSION: Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community's susceptibility to symptomatic malaria episodes after the screening campaigns had finished. These results highlight the importance of further exploratory studies to better understand the dynamics of disease transmission in the context of malaria elimination. PMID- 24215307 TI - Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin. AB - N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is hydro soluble chitosan (CS) derivative, which can be obtained by the reaction between epoxypropyl trimethyl ammonium chloride (ETA) and CS. The preparation parameters for the synthesis of HTCC were optimized by orthogonal experimental design. ETA was successfully grafted into the free amino group of CS. Grafting of ETA with CS had great effect on the crystal structure of HTCC, which was confirmed by the XRD results. HTCC displayed higher capability to form nanoparticles by crosslinking with negatively charged sodium tripolyphosphate (TPP). Ribavrin- (RIV-) loaded HTCC nanoparticles were positively charged and were spherical in shape with average particle size of 200 nm. More efficient drug encapsulation efficiency and loading capacity were obtained for HTCC in comparison with CS, however, HTCC nanoparticles displayed faster release rate due to its hydro-soluble properties. The results suggest that HTCC is a promising CS derivative for the encapsulation of hydrophilic drugs in obtaining sustained release of drugs. PMID- 24215308 TI - Effect of smoking on choroidal thickness in healthy smokers. AB - PURPOSE: To evaluate the acute and chronic effects of cigarette smoking on the choroidal thickness of young male smokers with smoking histories exceeding 10 years using spectral domain optical coherence tomography (SD OCT). MATERIALS AND METHODS: The right eyes of 40 never-smoking and 30 smoking healthy subjects were included in this study. We measured the choroidal thicknesses of the never smoking subjects as a control group. The choroidal thicknesses of the smoking subjects were measured before, 5, 30 and 60 min after smoking. Choroidal thickness measurements were taken at the fovea and at two points that were 1500 um nasal and temporal to the fovea. RESULTS: No significant difference was found for the retinal thickness, choroidal thicknesses, spherical equivalent, intraocular pressure and central corneal thickness of the smokers and non-smokers (p > 0.05 for all). In the measurements that were taken after smoking, a statistically significant increase was found in choroidal thickness that was observed between 0 and 5 min for the central, nasal and temporal segments (p < 0.001 for all). CONCLUSIONS: Smoking caused acute, significant increase in choroidal thickness that returned to baseline levels after 1 h. The choroidal and retinal thicknesses did not differ significantly between the healthy young smokers and non-smokers. PMID- 24215309 TI - Diabetes, cancer and treatment - a mini-review. AB - AIM: To conduct a systematic review of the published pre-clinical in vitro and in vivo evidence for plausible mechanisms underlying the risk of cancer associated with insulin and insulin analogues. MATERIAL AND METHODS: The review was developed according to the PRISMA guidelines. A systematic search of Pubmed was performed using the key words: "insulin analogue", "insulin derative", "insulin homologue", "glargine", "Lantus", "degludec", "tresiba", "NPH", "lispro", "humalog", "detemir", "levemir", "glulisine", "apidra", "aspart", "novolog", "insulin treatment", "diabetes treatment", "insulin therapy" or "diabetes therapy" combined with "neoplasia", "tumor", "cancer", "carcinoma", "malignan*", "carcinog*" or " mitoge*". Eligible studies were those reporting on potential biological mechanisms, studies reporting on statistical or epidemiological associations were excluded. RESULTS: Per October 8, 2013, the search produced 28,276 hits in Pubmed. All studies were either mechanistic speculations based on epidemiological association studies, a few randomized controlled trials (several unpublished), or non-human studies (cell cultures or animal studies). The evidence level in human terms was low. CONCLUSION: In general many studies on pre clinical in vitro and in vivo evidence for plausible mechanisms underlying the risk of cancer associated with insulin and insulin analogues exist. However, the level of evidence of a causal association between diabetes and the treatment of diabetes and cancer is low. PMID- 24215310 TI - Use of biguanides and the risk of colorectal cancer: a register-based cohort study. AB - Observational studies have shown conflicting results on the potential protecting effect of biguanide use with the risk of colorectal neoplasms. In addition, the cellular mechanism can either support or oppose biguanides influence on colorectal carcinoma. Our objective was to evaluate the association between biguanide use and colorectal carcinoma. A population-based cohort study using healthcare data from the Danish National database (1996-2007), was conducted. Oral antidiabetic drug users (n = 177,281) were matched 1:3 with a population based reference group. Cox proportional hazard models estimated hazard ratios (HRs) of colorectal carcinoma. Stratification was performed to analyse the risk of colorectal cancer in current biguanide users. Two sub-analyses were performed, to investigate the risk of colorectal cancer associated with discontinuous and prolonged use of biguanides. Instead of a protective effect, we found that current biguanide users had a 1.2-fold increased risk of colorectal cancer (HR = 1.19, 95% CI = 1.08-1.30) as compared with the non-diabetes reference group. Prolonged use was not inversely associated with colorectal cancer either. When studying colorectal risk with biguanides, the underlying T2DM should be taken into account since a 1.3-1.6-fold increased risk was found in oral antidiabetic drug users compared to controls unexposed to diabetic medication. This study could not detect a protective effect of biguanide use with colorectal cancer. Therefore, this study does not support a further investigation of the effectiveness of biguanides to prevent colorectal carcinoma in clinical studies. PMID- 24215311 TI - Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies. AB - BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS): POPULATION: diabetes patients. EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. OUTCOME: Any incident cancer. STUDY DESIGN: Cohort and case-control studies. RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk. PMID- 24215313 TI - Editorial: diabetes and cancer - disease, drugs or deception? PMID- 24215314 TI - The post hoc use of randomised controlled trials to explore drug associated cancer outcomes: methodological challenges. AB - INTRODUCTION: Drug-induced cancer risk is of increasing interest. Both observational studies and data from clinical trials have linked several widely used treatments to cancer. When a signal for a potential drug-cancer association is generated, substantiation is required to assess the impact on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of Randomised controlled trials (RCTs) designed for other purposes. METHODOLOGICAL CHALLENGES TO CONSIDER: We set out to perform a post-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between exposure and potential confounders. Considering these challenges, we concluded that using the data would not enlighten the discussion about insulin use and cancer risk and only serve to further complicate any understanding. Therefore, we decided to use our experience to illustrate methodological challenges, which need to be addressed when re analysing trial data for cancer related outcomes. CONCLUSION: Substantial amount of information on cancer outcomes is available from RCTs. Hence, making use of such data could save time and spare patients from inclusion in further trials. However, methodological challenges must be addressed to enhance the likelihood of reliable conclusions. Advantages of post-hoc analyses of RCTs include quality of data collected and sometimes randomisation to exposure of interest. Limitations include confounding and sample size, which is fixed to suit the purposes of the trial, insufficient duration of exposure and identification of underlying biological mechanisms relating treatment to cancer to formulate the most appropriate post-hoc study design. PMID- 24215315 TI - Use of thiazolidinediones and risk of bladder cancer: disease or drugs? AB - BACKGROUND: Pioglitazone, a drug for the treatment of type 2 diabetes mellitus has been associated with bladder cancer in observational studies. Diabetes mellitus itself has also been linked with bladder cancer. The objective was to estimate the risk of bladder cancer for diabetic patients using thialozidinediones (TZDs) compared with patients in other treatment stages of the disease. METHODS: We performed a population-based cohort study (1996-2007) in the Danish National Health Registers. Oral antidiabetic drug users (n=179,056) were matched 1:3 by sex and year of birth to non-users. Hazard ratios (HRs) of bladder cancer were estimated using Cox proportional hazards models. Time-dependent adjustments were made for age, comorbidity, and drug use. Four different treatment stages were defined: current use of either a biguanide or a sulfonylureum (stage 1), current use of a biguanide and a sulfonylureum at the same time (stage 2), current use of TZDs (stage 3) and current use of insulin (stage 4). RESULTS: Compared with non-diabetic controls, patients using antidiabetic medication experienced a 1.3-fold increased risk of bladder cancer (adjusted HR 1.3 [95%CI 1.2-1.4]). No major differences were observed between the different treatment stages. The risk of bladder cancer varied between 1.2 [95%CI 1.0-1.4] in stage 4 and 1.4 [95%CI 1.3-1.6] in stage 1. The risk of bladder cancer with TZD use (stage 3) was similar to the other groups (adjusted HR 1.3 [95%CI 0.6-2.7]). INTERPRETATION: The association between TZD use and bladder cancer is probably confounded by the underlying disease. PMID- 24215312 TI - CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis. AB - BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer". STUDY ELIGIBILITY CRITERIA: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. RESULTS: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). LIMITATIONS: Publication bias seemed to be present. Only published data were used in the analyses. CONCLUSIONS: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer. PMID- 24215316 TI - Use of metformin and survival of diabetic women with breast cancer. AB - OBJECTIVE: This study was set out to determine whether metformin use influences survival in breast cancer patients treated with antidiabetic drugs as compared to non-users. RESEARCH DESIGN AND METHODS: We used data from the Danish national registries (1996-2008) to identify adult female patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Coxproportional hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions. RESULTS: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of death for 152 cases. Compared to non use, current metformin treatment was associated with a significant reduction in overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer specific mortality, a non-significant risk reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed in the first 12 months after discontinuation of metformin. CONCLUSIONS: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these findings is needed. PMID- 24215317 TI - Revisiting the acute performance of the 5086 MRI lead: coincidences or signs? PMID- 24215318 TI - The interaction between signal regulatory protein alpha (SIRPalpha) and CD47: structure, function, and therapeutic target. AB - CD47 is a broadly expressed membrane protein that interacts with the myeloid inhibitory immunoreceptor SIRPalpha (also termed CD172a or SHPS-1). SIRPalpha is the prototypic member of the SIRP paired receptor family of closely related SIRP proteins. Engagement of SIRPalpha by CD47 provides a downregulatory signal that inhibits host cell phagocytosis, and CD47 therefore functions as a "don't-eat-me" signal. Here, we discuss recent structural analysis of CD47-SIRPalpha interactions and implications of this for the function and evolution of SIRPalpha and paired receptors in general. Furthermore, we review the proposed roles of CD47-SIRPalpha interactions in phagocytosis, (auto)immunity, and host defense, as well as its potential significance as a therapeutic target in cancer and inflammation and for improving graft survival in xenotransplantation. PMID- 24215320 TI - Nano-gold diggers: Au-assisted SiO(2)-decomposition and desorption in supported nanocatalysts. AB - An investigation of the thermal stability of size-selected Au nanoparticles (NPs) synthesized via inverse micelle encapsulation and deposited on SiO2(4 nm)/Si(100) is presented. The size and mobility of individual Au NPs after annealing at elevated temperatures in ultrahigh vacuum (UHV) was monitored via atomic force microscopy (AFM). An enhanced thermal stability against coarsening and lack of NP mobility was observed up to 1343 K. In addition, a drastic decrease in the average NP height was detected with increasing annealing temperature, which was not accompanied by the sublimation of Au atoms/clusters in UHV. The apparent decrease in the Au NP height observed is assigned to their ability to dig vertical channels in the underlying SiO2 support. More specifically, a progressive reduction in the thickness of the SiO2 support underneath and in the immediate vicinity of the NPs was evidenced, leading to NPs partially sinking into the SiO2 substrate. The complete removal of silicon oxide in small patches was observed to take place around the Au NPs after annealing at 1343 K in UHV. These results reveal a Au-assisted oxygen desorption from the support via reverse oxygen spillover to the NPs. PMID- 24215321 TI - The sense of position and movement in the knee joint during voluntary movements. AB - The aim of the paper was to assess body position reproduction as well as jump height during an intended movement, together with an assessment of the influence of factors that disturb this process. Factors disturbing the jump were related to with the reproduction of different knee joint angles (90 degrees or 120 degrees ); different muscle activity in performed jumps: SJ with no countermovement and CMJ with countermovement; as well as with and without visual (VC) of control movement (nVC) - eyes covered. Nineteen subjects aged twenty-one years participated in the experiment. Jump height (h) was calculated on the basis of a reaction force (R) of the base, as registered with a tensometric platform. Two dimensional cinematographic analysis was used to assess the reproduction of angular position in the knee joint. A significant factor determining the level of position reproduction during voluntary movements was the imposed angle as well as the character of muscle activity. The biggest difficulty of developing maximum heights occurred during jumps with disturbed visual control (eyes shut). PMID- 24215322 TI - Round cell sarcomas beyond Ewing: emerging entities. AB - Primitive small blue round cell tumours (SBRCT) of childhood and young adults have been problematic to diagnose and classify. Diagnosis is also complicated in cases with atypical morphology, aberrant immunoprofiles and unusual clinical presentations. Even with the increased use of ancillary techniques in archival material, such as immunohistochemistry and molecular/genetic methods, a proportion of these tumours cannot be subclassified into specific histological types. A subset of tumours resembling microscopically the Ewing sarcoma family of tumours (EFT), being composed of primitive small round cells and occurring in paediatric or young adult age groups, remain unclassified, being negative for EWSR1, SS18(SYT), DDIT3(CHOP) and FOXO1(FKHR) gene rearrangements by FISH/RT-PCR. A small number of cases sharing the undifferentiated EFT appearance have been characterized recently carrying BCOR-CCNB3 or CIC-DUX4 fusions. However, based on the somewhat limited number of cases, it remains unclear if these newly defined genetic entities belong to any of the pre-existing clinicopathological disorders or represent altogether novel conditions. This review presents the latest molecular findings related to these SBRCTs, beyond the common EWSR1-ETS fusions. Specific attention has been paid to morphological features not associated typically with classic EFT, and the value of ancillary tests that can be applied when dealing with EWSR1-negative SBRCTs is discussed. PMID- 24215323 TI - Applications of collaborative helping maps: supporting professional development, supervision and work teams in family-centered practice. AB - Collaborative, family-centered practice has become an influential approach in helping efforts across a broad spectrum of human services. This article draws from previous work that presented a principle-based, practice framework of Collaborative Helping and highlighted the use of Collaborative Helping maps as a tool both to help workers think their way through complex situations and to provide a guideline for constructive conversations between families and helpers about challenging issues. It builds on that work to examine ways to utilize Collaborative Helping maps at worker, supervisory, and organizational levels to enhance and sustain collaborative, family-centered practice and weave its core values and principles into the everyday fabric of organizational cultures in human service agencies and government agencies that serve poor and marginalized families and communities. PMID- 24215324 TI - When does action comprehension need motor involvement? Evidence from upper limb aplasia. AB - Motor theories of action comprehension claim that comprehending the meaning of an action performed by a conspecific relies on the perceiver's own motor representation of the same action. According to this view, whether an action belongs to the motor repertoire of the perceiver should impact the ease by which this action is comprehended. We tested this prediction by assessing the ability of an individual (D.C.) born without upper limbs to comprehend actions involving hands (e.g., throwing) or other body parts (e.g., jumping). The tests used a range of different visual stimuli differing in the kind of information provided. The results showed that D.C. was as accurate and fast as control participants in comprehending natural video and photographic presentations of both manual and nonmanual actions, as well as pantomimes. However, he was selectively impaired at identifying point-light animations of manual actions. This impairment was not due to a difficulty in processing kinematic information per se. D.C. was indeed as accurate as control participants in two additional tests requiring a fine-grained analysis of an actor's arm or whole-body movements. These results challenge motor theories of action comprehension by showing that the visual analysis of body shape and motion provides sufficient input for comprehending observed actions. However, when body shape information is sparsely available, motor involvement becomes critical to interpret observed actions. We suggest that, with natural human movement stimuli, motor representations contribute to action comprehension each time visual information is incomplete or ambiguous. PMID- 24215325 TI - Novel angiotensin I-converting enzyme inhibitory peptides derived from an edible mushroom, Pleurotus cystidiosus O.K. Miller identified by LC-MS/MS. AB - BACKGROUND: Angiotensin I-converting enzyme (ACE) inhibitors have been reported to reduce mortality in patients with hypertension. Compared to chemosynthetic drugs, ACE inhibitors derived from natural sources such as food proteins are believed to be safer for consumption and to have fewer adverse effects. Some edible mushrooms have been reported to significantly reduce blood pressure after oral administration. In addition, mushrooms are known to be rich in protein content. This makes them a potential source of ACE inhibitory peptides. Hence, the objective of the current study was to isolate and characterise ACE inhibitory peptides from an edible mushroom, Pleurotus cystidiosus. METHODS: ACE inhibitory proteins were isolated from P. cystidiosus based on the bioassay guided purification steps, i.e. ammonium sulphate precipitation, reverse phase high performance liquid chromatography and size exclusion chromatography. Active fraction was then analysed by LC-MS/MS and potential ACE inhibitory peptides identified were chemically synthesized. Effect of in vitro gastrointestinal digestions on the ACE inhibitory activity of the peptides and their inhibition patterns were evaluated. RESULTS: Two potential ACE inhibitory peptides, AHEPVK and GPSMR were identified from P. cystidiosus with molecular masses of 679.53 and 546.36 Da, respectively. Both peptides exhibited potentially high ACE inhibitory activity with IC50 values of 62.8 and 277.5 MUM, respectively. SEC chromatograms and BIOPEP analysis of these peptides revealed that the peptide sequence of the hexapeptide, AHEPVK, was stable throughout gastrointestinal digestion. The pentapeptide, GPSMR, was hydrolysed after digestion and it was predicted to release a dipeptide ACE inhibitor, GP, from its precursor. The Lineweaver-Burk plot of AHEPVK showed that this potent and stable ACE inhibitor has a competitive inhibitory effect against ACE. CONCLUSION: The present study indicated that the peptides from P. cystidiosus could be potential ACE inhibitors. Although these peptides had lower ACE inhibitory activity compared to commercial antihypertensive drugs, they are derived from mushroom which could be easily obtained and should have no side effects. Further in vivo studies can be carried out to reveal the clear mechanism of ACE inhibition by these peptides. PMID- 24215326 TI - Enantioselective [4 + 2] cycloaddition of cyclic N-sulfimines and acyclic enones or ynones: a concise route to sulfamidate-fused 2,6-disubstituted piperidin-4 ones. AB - A concise route to valuable sulfamate-fused 2,6-disubstituted piperidin-4-ones or 2,3-dihydropyridin-4(1H)-ones in good yield with high diastereo- and enantioselectivity is presented. The combination of chiral primary amine and o fluorobenzoic acid efficiently promoted an asymmetric [4 + 2] cycloaddition reaction of N-sulfonylimines and enones or ynones. The cycloaddition reaction between cyclic N-sulfonylimines and ynones is first reported. PMID- 24215327 TI - Sleep/wake patterns and circadian typology in preschool children based on standardized parental self-reports. AB - We studied the sleep/wake patterns and circadian typology of Japanese preschool children living in the Tokyo metropolitan area (193 boys and 190 girls, 4-6 years of age) from June to July 2012 based on a standardized parental self-reporting questionnaire. Our major findings are as follows: (1) sleep/wake timing was delayed, and the duration of nocturnal sleep (sleep period as well as time in bed) increased from that on scheduled days (weekdays) to that on free days (weekends) for all ages. (2) The duration of daily sleep (24 h), including daytime nap, was longer for 4-year-old children compared with that in 5- to 6 year-old children, but not significantly different between scheduled and free days within each age group. (3) The distribution of chronotypes was 36.3% for morning (M)-type, 48.8% for neither (N)-type and 11.2% for evening (E)-type, and this distribution was independent of sex or age. (4) Sleep/wake timing delays were observed from M-type and N-type to E-type during scheduled and free days. (5) The duration of nocturnal sleep decreased but increased for 24-h sleep time from M-type and N-type to E-type on scheduled days. (6) Sleep durations did not differ among chronotypes on free days. (7) Chronotypes were associated with parents' diurnal preferences, mealtimes and attendance at kindergartens or childcare centers but not with sex, age, season of birth, exposure to multimedia or exposure to morning sunlight in their bedrooms. When these results were compared with those for older children and adolescents, similar sleep/wake patterns and circadian typology were observed, although to a lesser degree, in children as young as 4-6 years of age. Napping may compensate, in part, for an accumulated weekday sleep deficit. The distribution of chronotypes was associated with differences in sleep/wake timing and duration and was influenced by the parents' diurnal preferences and lifestyles. Further research on preschool children is required to investigate whether circadian typology affects their behavioral, emotional and cognitive development. PMID- 24215328 TI - Novel thiazole derivatives: a patent review (2008 - 2012; Part 1). AB - INTRODUCTION: Thiazole is a well-known five-membered heterocyclic compound. Various methods have been worked out for its synthesis. In the last few decades, a lot of work has been done on thiazole ring in order to find new compounds related to this scaffold acting as an antioxidant, analgesic, anti-inflammatory, antimicrobial, antifungal, antiviral, diuretic, anticonvulsant, neuroprotective and antitumor or cytotoxic drugs with lesser side effects. This review presents the up to date development of different thiazole derivatives. AREAS COVERED: This review gives an account of the recent therapeutic patent literature (2008 - 2012) describing the applications of thiazole and its derivatives on selected activities. In this review, many of the therapeutic applications of thiazole derivatives reported in international patents have been discussed. In addition to selected biological data, some of pharmaceutical applications are also summarized. Because of the large number of patents registered in this period relative to thiazole derivatives the attention was focused, in this first part of the review, on inhibitors of phosphatidylinositol-3-kinase, inhibitors of protein kinase and derivatives modulating enzymes related to metabolism. EXPERT OPINION: This review of patented products presents the thiazole ring as the nucleus of the derivatives considered from a medicinal chemistry perspective. The applications are based firstly on the specific enzyme target with very low development in the disease treatment. Most of the described compounds are shown to have beneficial therapeutic effects but at the same time these compounds, selective for 'multi signaling pathway' targets, may also increase the side-effect potential. PMID- 24215329 TI - Treatment with corticosteroids and the risk of anastomotic leakage following lower gastrointestinal surgery: a literature survey. AB - AIM: Background Anastomotic leakage is a serious complication in colorectal surgery. Treatment with corticosteroids is known to impair wound healing but their effect on the healing of a colorectal anastomosis remains unclear, and studies have reported conflicting results. Objective The aim of this study was to evaluate the current evidence regarding the effect of corticosteroids on the risk of anastomotic leakage following colorectal surgery. METHOD: Search strategy A systematic review was conducted following a search of PubMed and Embase. Selection criteria Inclusion criteria were studies published in English and involving humans. A minimum cohort of 50 patients was required and anastomoses involving the ileum, colon and rectum were included. Studies that investigated corticosteroids as a risk factor for anastomotic leakage were included regardless of the duration and the dose of corticosteroids. Data Collection and analysis A comparison was conducted between anastomotic leakage in noncorticosteroid- and corticosteroid-treated patients. The main outcome measure was the risk of anastomotic leakage. RESULTS: Twelve studies with a total of 9564 patients were included in the review. In total, 1034 patients received corticosteroids in the preoperative period, and 344 patients were diagnosed with anastomotic leakage, 70 of whom had received corticosteroids. Six of the 12 studies showed an increased risk for anastomotic leakage in the corticosteroid group. Overall, the anastomotic leakage rate was 6.77% (95% CI: 5.48-9.06) in the corticosteroid group and 3.26% (95% CI: 2.94-3.58) in the noncorticosteroid group. CONCLUSION: Caution should be shown in patients scheduled for lower gastrointestinal surgery with anastomosis. PMID- 24215330 TI - Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. AB - BACKGROUND: Mitochondrial disorders are difficult to diagnose due to extreme genetic and phenotypic heterogeneities. METHODS: We explored the utility of targeted next-generation sequencing for the diagnosis of mitochondrial disorders in 148 patients submitted for clinical testing. A panel of 447 nuclear genes encoding mitochondrial respiratory chain complexes, and other genes inducing secondary mitochondrial dysfunction or that cause diseases which mimic mitochondrial disorders were tested. RESULTS: We identified variants considered to be possibly disease-causing based on family segregation data and/or variants already known to cause disease in twelve genes in thirteen patients. Rare or novel variants of unknown significance were identified in 45 additional genes for various metabolic, genetic or neurogenetic disorders. CONCLUSIONS: Primary mitochondrial defects were confirmed only in four patients indicating that majority of patients with suspected mitochondrial disorders are presumably not the result of direct impairment of energy production. Our results support that clinical and routine laboratory ascertainment for mitochondrial disorders are challenging due to significant overlapping non-specific clinical symptoms and lack of specific biomarkers. While next-generation sequencing shows promise for diagnosing suspected mitochondrial disorders, the challenges remain as the underlying genetic heterogeneity may be greater than suspected and it is further confounded by the similarity of symptoms with other conditions as we report here. PMID- 24215331 TI - Reduction of elevated cytokine levels in acute/acute-on-chronic liver failure using super-large pore albumin dialysis treatment: an in vitro study. AB - The removal of small water soluble toxins and albumin-bound toxins in acute liver failure patients (ALF) or acute-on-chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut-offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super-large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin-bound toxins were removed more efficiently using novel large (Emic2) to super-large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL-6 and tumor necrosis factor-alpha was drastically improved using super-large pore membranes. The Emic2 membrane predominantly removed IL-6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super-large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified. PMID- 24215332 TI - Depression as a risk factor for cancer: from pathophysiological advances to treatment implications. AB - Innate immune activation and inflammation have been posited to play a role in the pathophysiology of both depression and neoplastic growth. Cancer patients experience a threefold higher rate of depression than the general population within the first five years of diagnosis. Chronic depression is associated with increased cancer risk and shortened survival. Although the precise cellular and molecular mechanisms of this bidirectional relationship remain unclear, elevated concentrations of circulating plasma proinflammatory cytokines associated with depression may mediate the neuroendocrine, neural, and immune pathways that account for the relationship. Proinflammatory cytokines, in turn, are known to modulate key neurobiological correlates of depression including hypothalamic pituitary-adrenal (HPA) axis dysregulation, monoamine neurotransmitter metabolism, and limbic system activity. Research is needed to determine whether optimal depression treatment improves cancer survival and to develop antidepressant strategies that target molecular and cellular mechanisms mediating inflammation and the neurobiological pathways influenced by the proinflammatory cytokines. PMID- 24215333 TI - Incidence of postembolization syndrome after complete renal angioinfarction: a single-institution experience over four years. AB - OBJECTIVE: Renal angioinfarction (RAI) has been used for various indications in the management of renal tumors. While historically used for palliation of local symptoms (pain or hematuria), this technique has theoretical use in facilitating radical nephrectomy by allowing early ligation of the renal vein, decreasing blood loss and creating edema in resection planes. A common impediment to embolization is the development of postembolization syndrome (PES), which has been reported to have an incidence as high as 89%. This study reports the authors' experience with RAI as a safe palliative and adjunctive procedure over 4 years. MATERIAL AND METHODS: From 2008 to 2011, 113 patients underwent complete RAI at Washington Hospital Center for palliative or adjunctive therapy by an interventional radiologist. Procedures were performed in a radiology suite using mild sedation with vascular access obtained by femoral artery puncture. RAI was performed by subsegmental injection of polyvinyl alcohol particles. RESULTS: All 113 patients underwent successful RAI with confirmation of total arterial flow ablation via postprocedure arteriogram: 38 underwent embolization for preoperative adjunctive therapy, 34 for palliation of renal mass, 36 for trauma/hemorrhage and five for symptomatic renal artery pseudoaneurysm after partial nephrectomy. PES occurred in 33 out of 75 patients (44.0%), with symptomatic PES in only two patients (2.6%). No major complications (>Clavien grade III) occurred. Thirty-eight patients were excluded from analysis as they underwent radical nephrectomy within 24 h, preventing accurate assessment of PES. CONCLUSIONS: RAI is a safe and reliable procedure for palliation of renal masses, as an adjunctive procedure for radical nephrectomy, and for conservative management of renal hemorrhage or aneurysm. PES occurs in relatively few patients, with no major complications, and should not impede clinical consideration of this procedure. PMID- 24215334 TI - Quality by design approach for oral bioavailability enhancement of irbesartan by self-nanoemulsifying tablets. AB - The present investigation was aimed to develop self-nanoemulsifying tablets (SNETs) as novel nanosized solid oral dosage forms for Irbesartan (IRB). In the first part of the investigation, IRB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed using Capryol 90 - Cremophor RH40 - Transcutol P as three component (oil - surfactant - cosurfactant) SNEDDS system. On the basis of ternary phase diagram IRB-loaded SNEDDS were optimized by using Design of Experiments (DoE) and Principal component analysis (PCA) with amount of oil and surfactant: cosurfactant ratio (Km) as factors. The optimized batch of IRB-loaded SNEDDS comprised of 31.62% w/w of Capryol 90 as oil phase, 49.90% w/w Cremophor RH40 as surfactant and 18.48% w/w of Transcutol P as cosurfactant exemplified a mean globule size as 23.94 nm. Further, with an aim to provide enhanced patient compliance the optimized batch of liquid SNEDDS was transformed into SNETs by liquisolid compaction technique. Solid state characterization of IRB-loaded liquisolid mixtures revealed a decrease in the magnitude of crystallinity of IRB. The results of in vitro drug release study of optimized batch of IRB-loaded SNET illustrated a remarkable improvement in the dissolution rate as compared to marketed tablets (Avapro(r) 75). The results of in vivo pharmacokinetic study on Wister rats revealed 1.78-fold enhancement in oral bioavailability for IRB-loaded SNETs against marketed tablets. The present study proposed SNEDDS as one of the suitable approach for developing nanosized solid oral dosage forms of poorly water soluble drugs like Irbesartan. PMID- 24215335 TI - The effect of bevacizumab on wound healing modulation in an experimental trabeculectomy model. AB - PURPOSE: Glaucoma filtration surgery remains the most effective surgical procedure for lowering intraocular pressure (IOP) in uncontrolled glaucoma. Modulation of wound healing is critical to ensure long-term surgical success. This study aimed to determine if bevacizumab is an alternative agent for wound modulation in glaucoma surgery. MATERIALS AND METHODS: Forty-eight eyes of New Zealand rabbits were divided into four groups undergoing standard trabeculectomy surgery in the right eye. In group 1, balanced salt solution injections (0.1 ml) were performed into the bleb. Bevacizumab (0.1 ml, 1.25 mg) was injected into the bleb in group two and into the vitreous body in group three. Subconjunctival injections of 5-fluorouracil (5-FU) were performed into the non-bleb area in group four. Postoperatively; IOP, bleb size, bleb height, bleb vascularity were evaluated. Right eyes of two animals from each group were enucleated in 10th, 20th and 30th d postoperatively and evaluated histopathologically for inflammation, neovascularization and fibrosis. RESULTS: The length, the width and the height of the bleb in the group two were greater than other groups. Mean IOP values were lower in group two. IOP measurements in the operated eyes of group two were statistically significantly lower than the other groups until the 28th d. Inflammation (p = 0.030), neovascularization (p = 0.004) and fibrosis (p < 0.000) in group two were lower in histopathological evaluation. CONCLUSIONS: Post operative subconjunctival injection of bevacizumab is more effective than intravitreal bevacizumab or subconjunctival 5-FU injections for bleb survival. Furthermore, IOP is lower for a long period with lower level of fibrosis, which increases the success of trabeculectomy. PMID- 24215336 TI - An unusual cause of automatic mode switching in the absence of an atrial tachyarrhythmia. PMID- 24215337 TI - Late-onset bolus intravenous beta-lactam antibiotic adverse reaction: short-lived symptoms during drug administration and associated laboratory abnormalities. AB - BACKGROUND: In the 1970s, there were 2 reports of a late-onset adverse reaction during bolus infusions of benzyl penicillin, characterized by short-lived symptoms, most commonly abdominal pain. The mechanism is not known. We set out to further characterize this reaction. METHODS: We conducted a prospective observational study of all adult patients receiving bolus intravenous (IV) beta lactam antibiotics under the care of our Outpatient IV Antibiotic Service from 1 August 2007 to 31 January 2010, focusing on those who developed infusion-related symptoms. RESULTS: During the 30-month study, 11 of the 163 patients (7%) treated with bolus IV beta-lactam antibiotics developed a late-onset infusion-related adverse reaction. Six of 30 patients (20%) treated with benzyl penicillin developed this adverse reaction compared to 5 of 133 (4%) treated with any other beta-lactam antibiotic (p = 0.006). The median duration of beta-lactam antibiotic before reaction onset was 25 days. Abdominal pain occurred in 9 patients (82%), fever in 3 (27%), and rash in 5 (45%). Seven patients (64%) developed a combination of thrombocytopenia, neutropenia, and/or lymphopenia and 6 (55%), elevated liver enzymes. CONCLUSIONS: This adverse reaction, occurring late during prolonged IV bolus beta-lactam treatment, is most often characterized by short lived abdominal pain occurring at the time of infusion and is more common in patients receiving benzyl penicillin. It is frequently associated with cytopenias and elevated liver enzymes. It may have both immunological and non-immunological mechanisms. PMID- 24215339 TI - Modeling and stress analyses of a normal foot-ankle and a prosthetic foot-ankle complex. AB - Total ankle replacement (TAR) is a relatively new concept and is becoming more popular for treatment of ankle arthritis and fractures. Because of the high costs and difficulties of experimental studies, the developments of TAR prostheses are progressing very slowly. For this reason, the medical imaging techniques such as CT, and MR have become more and more useful. The finite element method (FEM) is a widely used technique to estimate the mechanical behaviors of materials and structures in engineering applications. FEM has also been increasingly applied to biomechanical analyses of human bones, tissues and organs, thanks to the development of both the computing capabilities and the medical imaging techniques. 3-D finite element models of the human foot and ankle from reconstruction of MR and CT images have been investigated by some authors. In this study, data of geometries (used in modeling) of a normal and a prosthetic foot and ankle were obtained from a 3D reconstruction of CT images. The segmentation software, MIMICS was used to generate the 3D images of the bony structures, soft tissues and components of prosthesis of normal and prosthetic ankle-foot complex. Except the spaces between the adjacent surface of the phalanges fused, metatarsals, cuneiforms, cuboid, navicular, talus and calcaneus bones, soft tissues and components of prosthesis were independently developed to form foot and ankle complex. SOLIDWORKS program was used to form the boundary surfaces of all model components and then the solid models were obtained from these boundary surfaces. Finite element analyses software, ABAQUS was used to perform the numerical stress analyses of these models for balanced standing position. Plantar pressure and von Mises stress distributions of the normal and prosthetic ankles were compared with each other. There was a peak pressure increase at the 4th metatarsal, first metatarsal and talus bones and a decrease at the intermediate cuneiform and calcaneus bones, in prosthetic ankle-foot complex compared to normal one. The predicted plantar pressures and von Misses stress distributions for a normal foot were consistent with other FE models given in the literature. The present study is aimed to open new approaches for the development of ankle prosthesis. PMID- 24215340 TI - Particle carriers for combating multidrug-resistant cancer. AB - Multidrug resistance (MDR) in tumors accounts for significant treatment failure. Particle carriers offer potential benefits for treating cancer, including the ability to target tumors and to deliver multiple cargo, providing opportunities to overcome drug resistance. In this Perspective, we provide a brief introduction to the MDR mechanisms and implications of tumor heterogeneity that contribute to drug resistance. We also highlight recent advances in the design of particles aimed at treating resistant tumors through particle-based codelivery of therapeutics. Finally, we discuss future directions, where an increased understanding of the tumor biology can be leveraged to develop new and improved particle-based cancer therapies. PMID- 24215341 TI - Toward relationship-directed parenting: an example of North American born second generation Korean-American mothers and their partners. AB - Historically, parenting has been constructed hierarchically; however, contemporary parenting models frequently emphasize parenting as relationship (Siegel & Hartzell [2004] Parenting from the inside out: How a deeper self understanding can help you raise children who thrive; Tuttle, Knudson-Martin, & Kim [2012] Family Process, 51, 73-89). Drawing on interviews with 20 North American born second-generation Korean-American mothers and their partners, and sensitized by TP-CRO, a social constructionist framework for conceptualizing parent-child relational orientations, this grounded theory analysis identified three main processes that facilitate relational connection as a parenting orientation rather than the rule-directed approach historically associated with first-generation immigrant Asian families. These include: (a) emphasizing dominant culture values; (b) inviting open communication; and (c) promoting mutuality. Results also show how parents integrate collectivist cultural values of their first generation immigrant parents' traditional culture into North American parenting ideals with which they primarily identify. The study demonstrates the usefulness of the TP-CRO for understanding parent-child relationships within multicultural parenting contexts and offers suggestions for working with second-generation Korean families. PMID- 24215342 TI - Chromatin remodeling: a new landscape to treat harmful alcohol-use disorders. PMID- 24215344 TI - A pharmacophore-based virtual screening approach for the discovery of Trypanosoma cruzi GAPDH inhibitors. AB - BACKGROUND: Chagas disease is a major cause of morbidity and death for millions of people in Latin America. The drugs currently available exhibit poor efficacy and severe side effects. Therefore, there is an urgent need for new, safe and effective drugs against Chagas disease. The vital dependence on glycolysis as energy source makes the glycolytic enzymes of Trypanosoma cruzi, the causative agent of Chagas disease, attractive targets for drug design. In this work, glyceraldehyde-3-phosphate dehydrogenase from T. cruzi (TcGAPDH) was employed as molecular target for the discovery of new inhibitors as hits. RESULTS: Integrated protein-based pharmacophore and structure-based virtual screening approaches resulted in the identification of three hits from three chemical classes with moderate inhibitory activity against TcGAPDH. The inhibitors showed IC50 values in the high micromolar range. CONCLUSION: The new chemotypes are attractive molecules for future medicinal chemistry efforts aimed at developing new lead compounds for Chagas disease. PMID- 24215345 TI - 5-alkyl-1,3-oxazole derivatives of 6-amino-nicotinic acids as alkyl ester bioisosteres are antagonists of the P2Y12 receptor. AB - BACKGROUND: Recently, we reported ethyl nicotinates as antagonists of the P2Y12 receptor, which is an important target in antiplatelet therapies. A potential liability of these compounds was their generally high in vivo clearance due to ethyl ester hydrolysis. RESULTS: Shape and electrostatic similarity matching was used to select five-membered heterocycles to replace the ethyl ester functionality. The 5-methyl and 5-ethyl-oxazole bioisosteres retained the sub micromolar potency levels of the parent ethyl esters. Many oxazoles showed a higher CYP450 dependent microsomal metabolism than the corresponding ethyl esters. Structure activity relationship investigations supported by ab initio calculations suggested that a correctly positioned alkyl substituent and a strong hydrogen bond acceptor were necessary structural motifs for binding. In rat pharmacokinetics, the low clearance was retained upon replacement of an ethyl ester with a 5-ethyl-oxazole. CONCLUSION: The use of shape and electrostatic similarity led to the successful replacement of a metabolically labile ethyl ester functionality with 5-alkyl-oxazole bioisosteres. PMID- 24215346 TI - Calpain-1 inhibitors for selective treatment of rheumatoid arthritis: what is the future? AB - Effective small-molecule treatment of inflammatory diseases remains an unmet need in medicine. Current treatments are either limited in effectiveness or invasive. The latest biologics prevent influx of inflammatory cells to damaged tissue. Calpain-1 is a calcium-activated cysteine protease that plays an important role in neutrophil motility. It is, therefore, a potential target for intervention in inflammatory disease. Many inhibitors of calpains have been developed but most are unselective and so unsuitable for drug use. However, recent series of alpha mercaptoacrylate inhibitors target regulatory domains of calpain-1 and are much more specific. These compounds are effective in impairing the cell spreading mechanism of neutrophils in vitro and raise the possibility of treating rheumatoid arthritis with a pill; however, challenges still remain. Improved bioavailability is needed and solution of their precise mode of action should prompt the development of specific calpain-1 screens for novel classes of inhibitors. PMID- 24215347 TI - Cucurbit[n]uril type hosts for the reversal of steroidal neuromuscular blocking agents. AB - The ideal neuromuscular blocking agent (NMBA) is regarded as being a non depolarizing equivalent of succinylcholine, having a rapid onset and short duration of action, with minimal side effects. In the absence of a single drug, the administration of an aminosteroid NMBA, such as rocuronium, followed by reversal using an acetylcholinesterase inhibitor, such as neostigmine, is commonly employed. A different and safer approach to rapidly reversing the action of the NMBA, by encapsulating it with a macrocyclic or acyclic host molecule, such as the cyclodextrin sugammadex or more recently, cucurbituril-type hosts such as cyclic cucurbit[7]uril and the acyclic glycoluril tetramer calabadion 1, is described. PMID- 24215348 TI - Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases. AB - There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates. PMID- 24215349 TI - Use of zebrafish in chemical biology and drug discovery. AB - The zebrafish (Danio rerio) is a small, tropical, freshwater fish that has emerged as a powerful vertebrate model organism for studying genetics and development. Its small size, transparency, cost-effectiveness, close genome homology to humans compared with invertebrates, and capacity for genetic manipulation are all valuable attributes for an excellent animal model. There are additional advantages for using zebrafish specifically in drug discovery, including ease of exposure to chemicals in water. In effect, zebrafish can bridge a gap between in vitro and mammalian work, reducing the use of larger animals and attrition rates. In the drug-discovery process, zebrafish can be used at many stages, including target identification and validation, identification of lead compounds, studying structure-activity relationships and drug safety profiling. In this review, we highlight the potential for the zebrafish model to make the drug-discovery process simpler, more effective and cost-efficient. PMID- 24215351 TI - Jumping to delusions in early psychosis. AB - INTRODUCTION: Patients with delusions typically seek less information when making decisions than controls ("jumping-to-conclusions", JTC) and paradoxically over adjust to counter-evidence on probabilistic reasoning tasks. Previous studies have examined JTC bias across the delusion-prone continuum, but have not considered the co-occurrence of both biases at early stages of psychosis. This was our aim. METHOD: Twenty-three early psychosis patients and 19 healthy controls completed two versions of the probabilistic reasoning task: a "draws-to decision" version (to assess JTC) and a "graded-estimates" version (to assess over-adjustment). Both versions have been used previously with clinically delusional people with schizophrenia. IQ, memory and executive function were also examined. RESULTS: Patients took fewer trials to reach a decision in the draws-to decision version and showed greater over-adjustment to counter-evidence in the graded-estimates version than controls. Across groups, those who jumped to conclusions showed greater over-adjustment. Poor executive function predicted more extreme biases in controls but not in patients. Task performances were unrelated to memory. Similar results were evident in patient and control subgroups matched on IQ, and years of formal education. CONCLUSIONS: A jumping-to conclusions bias and an over-adjustment bias co-occurred in the early psychosis patients. Implications are discussed concerning the role of such biases in delusion-proneness. PMID- 24215352 TI - Discovery of potent Mcl-1/Bcl-xL dual inhibitors by using a hybridization strategy based on structural analysis of target proteins. AB - Mcl-1 and Bcl-xL are crucial regulators of apoptosis, therefore dual inhibitors of both proteins could serve as promising new anticancer drugs. To design Mcl 1/Bcl-xL dual inhibitors, we performed structure-guided analyses of the corresponding selective Mcl-1 and Bcl-xL inhibitors. A cocrystal structure of a pyrazolo[1,5-a]pyridine derivative with Mcl-1 protein was successfully determined and revealed the protein-ligand binding mode. The key structure for Bcl-xL inhibition was further confirmed through the substructural analysis of ABT-263, a representative Bcl-xL/Bcl-2/Bcl-w inhibitor developed by Abbott Laboratories. On the basis of the structural data from this analysis, we designed hybrid compounds by tethering the Mcl-1 and Bcl-xL inhibitors together. The results of X-ray crystallographic analysis of hybrid compound 10 in complexes with both Mcl-1 and Bcl-xL demonstrated its binding mode with each protein. Following further optimization, compound 11 showed potent Mcl-1/Bcl-xL dual inhibitory activity (Mcl-1, IC50 = 0.088 MUM; and Bcl-xL, IC50 = 0.0037 MUM). PMID- 24215353 TI - Total synthesis of (-)-ecklonialactone B. AB - The total synthesis of (-)-ecklonialactone B as well as the 9,10-dihydro derivative by two different strategies is reported. The catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers delivered elaborated alpha-keto ester building blocks. Ring-closing metatheses, including a notable diastereotopos-differentiating variant, a B-alkyl Suzuki-Miyaura cross-coupling reaction and a regio- and diastereoselective last-step epoxidation are key contributors. PMID- 24215354 TI - Cytotoxic effect of Alpinia scabra (Blume) Naves extracts on human breast and ovarian cancer cells. AB - BACKGROUND: Alpinia scabra, locally known as 'Lengkuas raya', is an aromatic, perennial and rhizomatous herb from the family Zingiberaceae. It is a wild species which grows largely on mountains at moderate elevations in Peninsular Malaysia, but it can also survive in the lowlands like in the states of Terengganu and Northern Johor. The present study reports the cytotoxic potential of A. scabra extracts from different parts of the plant. METHODS: The experimental approach in the present study was based on a bioassay-guided fractionation. The crude methanol and fractionated extracts (hexane, chloroform and water) from different parts of A. scabra (leaves, rhizomes, roots and pseudo stems) were prepared prior to the cytotoxicity evaluation against human ovarian (SKOV-3) and hormone-dependent breast (MCF7) carcinoma cells. The identified cytotoxic extracts were then subjected to chemical investigations in order to identify the active ingredients. A normal human lung fibroblast cell line (MRC-5) was used to determine the specificity for cancerous cells. The cytotoxic extracts and fractions were also subjected to morphological assessment, DNA fragmentation analysis and DAPI nuclear staining. RESULTS: The leaf (hexane and chloroform) and rhizome (chloroform) extracts showed high inhibitory effect against the tested cells. Ten fractions (LC1-LC10) were yielded after purification of the leaf chloroform extract. Fraction LC4 which showed excellent cytotoxic activity was further purified and resulted in 17 sub-fractions (VLC1-VLC17). Sub-fraction VLC9 showed excellent cytotoxicity against MCF7 and SKOV-3 cells but not toxic against normal MRC-5 cells. Meanwhile, eighteen fractions (RC1-RC18) were obtained after purification of the rhizome chloroform extract, of which fraction RC5 showed cytotoxicity against SKOV-3 cells with high selectivity index. There were marked morphological changes when observed using phase-contrast inverted microscope, DAPI nuclear staining and also DNA fragmentations in MCF7 and SKOV-3 cells after treatment with the cytotoxic extracts and fractions which were indicative of cell apoptosis. Methyl palmitate and methyl stearate were identified in the hexane leaf extract by GC-MS analysis. CONCLUSIONS: The data obtained from the current study demonstrated that the cell death induced by cytotoxic extracts and fractions of A. scabra may be due to apoptosis induction which was characterized by apoptotic morphological changes and DNA fragmentation. The active ingredients in the leaf sub-fraction VLC9 and rhizome fraction RC5 may lead to valuable compounds that have the ability to kill cancer cells but not normal cells. PMID- 24215355 TI - Varenicline induced acute interstitial nephritis in the setting of idiopathic membranous glomerulonephritis. AB - BACKGROUND: Varenicline is a nicotinic receptor partial agonist indicated for the cessation of smoking. It is regarded as having no or minimal renal toxicity. A single case report has linked it to acute interstitial nephritis. CASE PRESENTATION: A 56 year-old female with a long-standing history of idiopathic membranous glomerulonephritis presented on routine follow-up with an unexpected rise in her serum creatinine from a stable baseline of 225 umol/L to 319 umol/L Biopsy revealed acute interstitial nephritis. There were no preceding clinical events other than the initiation of varenicline therapy three months prior. This was discontinued with no improvement in renal function. A ten week course of prednisone was initiated and creatinine levels returned to baseline. Shortly after prednisone therapy was completed, renal function worsened but the patient declined further immunosuppressive therapy. Exposure to varenicline therapy two years prior had also resulted in a reversible decline in kidney function. CONCLUSION: This is only the second case report to document varenicline-induced acute interstitial nephritis. A careful medication history and renal biopsy were essential in identifying the etiology of the acute kidney injury in this patient with a complex renal history. PMID- 24215357 TI - A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects. AB - Liver cancer has become one of the most common fatal cancers worldwide, with morbidity rates increasing each year. Wogonin (WG) is an attractive candidate for the development of new anti-cancer drugs. In this study, a novel glycyrrhetinic acid (GA)-modified WG liposome was developed for use in targeted anti-cancer therapy. Three types of WG preparations were investigated: free wogonin in solution (WG), passively targeted wogonin liposomes (WG-Lip) and GA-modified wogonin liposomes (GA-WG-Lip). The entrapment efficiency, size and zeta potential were measured. Cellular uptake, cytotoxicity, in vivo bio-distribution and anti tumor efficacy were also investigated. Addition of GA to the liposomes did not diminish the high entrapment efficiency observed in the liposomes without GA. GA WG-Lip showed the greatest uptake and had an IC50 value 1.46 times higher than that of WG-Lip. The GA-modified liposomes rapidly accumulated in the liver with a long retention time, and also displayed a better tumor inhibitory ratio than that of the unmodified liposomes. Overall, the data indicated that use of the GA modified WG liposomes conferred improvements in bio-distribution, accumulation at the tumor and therapeutic efficacy, perhaps due to increased receptor-mediated uptake of liposomes by liver-targeted cells. Together, these data show that GA-WG Lip is a promising means of targeted therapy for liver cancer. PMID- 24215358 TI - Revealing the binding structure of the protein corona on gold nanorods using synchrotron radiation-based techniques: understanding the reduced damage in cell membranes. AB - Regarding the importance of the biological effects of nanomaterials, there is still limited knowledge about the binding structure and stability of the protein corona on nanomaterials and the subsequent impacts. Here we designed a hard serum albumin protein corona (BSA) on CTAB-coated gold nanorods (AuNRs) and captured the structure of protein adsorption using synchrotron radiation X-ray absorption spectroscopy, microbeam X-ray fluorescent spectroscopy, and circular dichroism in combination with molecular dynamics simulations. The protein adsorption is attributed to at least 12 Au-S bonds and the stable corona reduced the cytotoxicity of CTAB/AuNRs. These combined strategies using physical, chemical, and biological approaches will improve our understanding of the protective effects of protein coronas against the toxicity of nanomaterials. These findings have shed light on a new strategy for studying interactions between proteins and nanomaterials, and this information will help further guide the rational design of nanomaterials for safe and effective biomedical applications. PMID- 24215359 TI - Comparison of ICD implantation in obese and nonobese patients. AB - BACKGROUND: Implantable defibrillator (ICD) therapy improves mortality in patients at risk for sudden cardiac death. Obese patients pose challenges during ICD implantation and may have an increased risk of procedure-related complications. The comparison of acute procedural success and safety of ICD implantation in obese and nonobese patients has not been previously reported. METHODS: A total of 181 patients underwent ICD implantation at a single institution. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m(2) . Acute safety and efficacy data were collected and analyzed from a prospectively maintained database, with retrospective chart review, as required. RESULTS: Among the 181 patients, 58 (32.0%) were obese. Mean BMI was 36.7 +/- 6.3 kg/m(2) among obese patients and was 24.6 +/- 3.1 kg/m(2) among nonobese patients (P < 0.001). Successful ICD implantation occurred in 58 of 58 (100%) obese patients and 122 of 123 (99.2%) nonobese patients (P = 1.0). A complication was observed in three of 58 (5.2%) obese patients and in seven of 123 (5.7%) nonobese patients (P = 1.0). Similarly, there was no difference in acute procedural success and safety in patients receiving a cardiac resynchronization therapy (CRT)-ICD. CONCLUSIONS: Acute success and safety of ICD implantation is similar in both obese and nonobese patients. This finding extended to patients treated with a CRT-ICD and among patients with extreme obesity. Obesity should probably not be a factor in determining whether a patient is a candidate for ICD implantation. PMID- 24215360 TI - Bulbourethral gland adenocarcinoma in a 25-year-old man without comorbidities: radical resection of proximal urethrae with Mitrofanoff-type appendicovesicostomy. AB - Adenocarcinoma of the paraurethral gland is a rare tumour with no published prevalence in male patients. This report presents a case of bulbourethral gland adenocarcinoma in a 25-year-old man without comorbidities. After resection of the proximal urethra, sphincter and prostate, Mitrofanoff-type appendicovesicostomy was performed. In this case, chemotherapy or radiation was not included in the treatment as the surgery was estimated to be radical. The patient achieved good surgical and quality of life results. This case shows that macroscopic haematuria should be examined even in young age groups without comorbidities. PMID- 24215356 TI - Risk of clinically significant depression in HIV-infected patients: effect of antiretroviral drugs. AB - OBJECTIVES: We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. METHODS: CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naive at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. RESULTS: In total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01-15.15] and 7.06 (95% CI 5.45-9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28-0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94; 95% CI 1.21-3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2-4 and > 4 years of ART was 0.72 (95% CI 0.36-1.44), 0.10 (95% CI 0.04-0.25) and 0.05 (95% CI 0.01-0.17), respectively, compared with ART-naive patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. CONCLUSIONS: The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens. PMID- 24215361 TI - Translational perspectives on perfusion-diffusion mismatch in ischemic stroke. AB - Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion-diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice. PMID- 24215363 TI - What is the reason for conflicting results for vancomycin minimum inhibitory concentration values of methicillin-resistant Staphylococcus aureus? PMID- 24215362 TI - Zinc finger protein in severe dry eye syndrome. AB - PURPOSE: Zinc finger protein known to induce squamous metaplasia and regulate vitamin A expression has been few investigated as tear protein. We investigated tear protein variations in patients with dry eye syndrome (DES). MATERIALS AND METHODS: Tears from healthy subjects as control and patients with DES were collected. Tear proteins were separated by one-dimensional electrophoresis. The protein bands were analyzed by nano liquid chromatography-mass spectrometry. RESULTS: Compared to the controls, significant down-regulation of lactoferrin and lysozyme was detected, while significant up-regulation was observed for serum albumin in patients with DES. DES grade 4 patients showed different protein patterns. Zinc-finger motif-enhancer binding-protein-1 gamma and bromodomain adjacent to zinc finger domain 2B were detected in DES grade 4 patients. CONCLUSIONS: Tear protein changes are valuable to diagnosis DES. Zinc finger proteins may be associated with pathophysiology of severe DES. Further studies are needed to better understand the relationship of zinc finger proteins in tear of patients with DES. PMID- 24215364 TI - The effect of short- and long-term vibration training on postural stability in men. AB - The study aimed to establish the short- and long-term effects of vibration on postural stability in young men. A single set of exercises and a 4-week vibration training were assessed for their impact on the center of foot pressure (COP) sway. The sample consisted of 49 male subjects randomly allocated to seven comparative groups, six of which exercised on a vibration platform whose parameters were set individually for the groups. Group VII was the control group. The stabilographic signal was recorded before the test commenced, after a single application of vibration, before the last set of exercises of the 4-week vibration training, immediately afterwards, as well as one week and one month after the training ended. The subjects were exposed to vibration 3 times a week for 4 weeks. Both a single application of vibration and the 4-week vibration training had an effect on all parameter values, but most changes were statistically insignificant. Group III was the only one where the COP sway in the anterior-posterior direction significantly increased after a single exposure to vibration and significantly decreased in both anterior-posterior and medio lateral planes one week after vibration training compared with the pre-test recordings. PMID- 24215365 TI - Effects of polymorphisms and haplotypes within the MSTN gene on duck growth trait. AB - Abstract 1. Polymorphisms of the duck MSTN gene were investigated in 413 individuals by DNA sequencing and polymerase chain reaction restriction fragment length polymorphism. Four single nucleotide polymorphisms (G129A, C324T, A981G and C1002A), with A981G and C1002A completely linked, were found in the coding region. 2. Association analysis showed that different genotypes of all the identified SNPs were significantly associated with duck growth rate from week 5, 6 and 2 for G129A, C324T and A981G (C1002A), respectively. The greatest difference in body weight was 180 g at week 9, 106 g at week 8 and 123 g at week 8, respectively, for the three SNP's. 3. Linkage disequilibrium (LD) analysis indicated that C324T, A981G and C1002A were in strong LD. Nine main diplotypes from the reconstructed five main haplotypes were observed, and different diplotypes were significantly associated with growth rate from week 1. Birds with the h1h1 diplotype exhibited the largest body weight from week 1 onwards. 4. It was concluded that the duck MSTN gene was associated with body weight and is an important candidate gene for duck growth. traits and marker-assisted selection. PMID- 24215366 TI - Three new compounds from the leaves of Liquidambar formosana. AB - Two new flavan glycosides, (2S)-5,7,4'-trihydroxyflavan-7-O-beta-D glucopyranoside and (2S)-5,7,4'-trihydroxyflavan-5-O-beta-D-glucopyranoside, and a new neolignan, (7S,8S)-3-methoxyl-3'-O-beta-D-glucopyrannosyl-4':8,5':7 diepoxyneolignan-4,9'-diol, were isolated from the leaves of Liquidambar formosana Hance. Their structures were elucidated on the basis of spectroscopic data and chemical evidence. PMID- 24215367 TI - Failure to benefit from target novelty during encoding contributes to working memory deficits in schizophrenia. AB - INTRODUCTION: Although working memory (WM) impairments are well documented in schizophrenic patients (PSZ), the underlying mechanisms are poorly understood. The aim of this study was to investigate the role of target salience during encoding to determine whether impaired visual attention in PSZ leads to poor WM. METHODS: Thirty-one PSZ and 28 demographically matched healthy controls (HC) performed a spatial delayed-response task. Attentional demands were manipulated during WM encoding by presenting high salient (novel) or low salient (familiar) targets. Participants also rated their level of response confidence at the end of each trial, allowing us to analyse different response types. RESULTS: WM was impaired in PSZ. Increasing target salience by increasing novelty improved WM performance in HC but not in PSZ. Poor WM performance in PSZ was largely due to an increase in the proportion of incorrect but high confident responses most likely reflecting a failure to encode the correct target. CONCLUSIONS: Our findings suggest that dysfunctions of non-mnemonic attentional processes during encoding contribute to WM impairments in schizophrenia and may represent an important target for cognitive remediation strategies. PMID- 24215368 TI - Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo. AB - We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-beta-D-ribose2'-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis. PMID- 24215369 TI - Engaging students and faculty: implications of self-determination theory for teachers and leaders in academic medicine. AB - BACKGROUND: Much of the work of teachers and leaders at academic health centers involves engaging learners and faculty members in shared goals. Strategies to do so, however, are seldom informed by empirically-supported theories of human motivation. DISCUSSION: This article summarizes a substantial body of motivational research that yields insights and approaches of importance to academic faculty leaders. After identification of key limitations of traditional rewards-based (i.e., incentives, or 'carrots and sticks') approaches, key findings are summarized from the science of self-determination theory. These findings demonstrate the importance of fostering autonomous motivation by supporting the fundamental human needs for autonomy, competence, and relatedness. In turn, these considerations lead to specific recommendations about approaches to engaging autonomous motivation, using examples in academic health centers. SUMMARY: Since supporting autonomous motivation maximizes both functioning and well-being (i.e., people are both happier and more productive), the approaches recommended will help academic health centers recruit, retain, and foster the success of learners and faculty members. Such goals are particularly important to address the multiple challenges confronting these institutions. PMID- 24215370 TI - Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions. AB - OBJECTIVES: Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first-line ritonavir-boosted, protease-inhibitor (PI/r) containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir-boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r. METHODS: In a retrospective assessment of HIV infected patients initiating ATV/r-containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation. RESULTS: A total of 202 patients [median age 33 years (interquartile range (IQR) 29-40 years); 52% female; median CD4 count 184 cells/MUL (IQR 107-280 cells/MUL); median HIV RNA 4.6 log10 HIV-1 RNA copies/mL (IQR 3.2-5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naive. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10-52) weeks on ART, with a median (IQR) UTrI duration of 10 (3-31) weeks. Fifty-four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies?mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3-9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3-4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re-suppressed on ATV/r reinitiation. CONCLUSIONS: In this PI-treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r-treated patients prior to ART reinitiation after UTrI. PMID- 24215372 TI - Donor-substituted nitrocyclopropanes: immediate ring-enlargement to cyclic nitronates. AB - The reaction of donor-substituted alkenes with alpha-diazo-alpha-nitro ethyl acetate under Rh catalysis was investigated; respective nitrocyclopropanes with a geminal ester functionality were generated in situ. Strong electron donors immediately led to ring-enlargement. In all cases, the nitro group was inserted forming cyclic nitronates whereas the ester moiety was not incorporated into the ring system. DFT studies revealed that the formation of cyclic nitronates is kinetically as well as thermodynamically favored over the formation of cyclic ketene acetals. PMID- 24215371 TI - Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke. AB - BACKGROUND: Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. METHODS: We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. RESULTS: Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). CONCLUSIONS: Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation. PMID- 24215373 TI - Effects of poly(ethylene glycol) grafting density on the tumor targeting efficacy of nanoparticles with ligand modification. AB - To evaluate the effects of poly(ethylene glycol) (PEG) grafting density on the tumor targeting efficacy of nanoparticles (NPs) with ligand modification, various amounts of PEG were conjugated to linoleic acid and poly(beta-malic acid) double grafted chitosan (LMC) NPs bearing similar substitution degree of folate (FA). Increased particle size, decreased surface charge, reduced contact angle, retarded drug release and suppressed protein adsorption of LMC NPs were detected after surface modification. Compared to LMC NPs, FA-modified LMC NPs (FA-LMC NPs) remarkably enhanced tumor specificity. For PEG-modified FA-LMC NPs, increased drug accumulation in tumor tissues and reduced cellular uptake were observed with the increase of PEG grafting density. In regard to in vivo antitumor efficacy, FA LMC NPs with moderate PEG grafting density (8.9%) significantly outperformed FA LMC NP. Therefore, PEG modification with moderate grafting density could be a promising approach to coordinating with the tumor targeting efficacy of ligand modified NPs. PMID- 24215374 TI - The benefit of a second burst antitachycardia sequence for fast ventricular tachycardia in patients with implantable cardioverter defibrillators. AB - BACKGROUND: In patients with implantable cardioverter defibrillators (ICDs), an empirical burst of antitachycardia pacing (ATP) is moderately effective in terminating fast ventricular tachycardias (FVTs). It is unknown whether, in the case of failure of a first burst, a second burst attempt increases the efficacy of the intervention, without increasing morbidity. Our aim was to evaluate the safety and efficacy of a strategy of programming successive ATP sequences for FVT episodes. METHODS: A prospective study evaluated the safety and effectiveness of programming successive ATP sequences for termination of FVT episodes (cycle lengths [CLs] 250-320 ms) treated by one ATP sequence and, in the event of failure, by successive ATP attempts or shocks. RESULTS: Over a median follow-up of 54 months, 267 FVT episodes (mean CL of 295 +/- 18 ms) were detected in 35 patients. Effectiveness of the first burst ATP was 64% (65% GEE-adjusted, where GEE is generalized estimating equation) and increased significantly to 83% (75% GEE-adjusted) with the second burst ATP sequence (P = 0.01). In the remaining 17% of FVT episodes with failure of the second ATP, successive bursts and shocks were required. Multivariate analysis showed that primary prevention ICD (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.9-14.5, P = 0.001), sinus rhythm (OR 4.34, 95% CI 1.4-13.4, P = 0.01), nonischemic cardiomyopathy (OR 2.36, 95% CI 1.2 4.8, P = 0.02), and longer VT CL (OR 1.32, 95% CI 1.1-1.6, P = 0.002) were independently associated with effectiveness of the first or second burst pacing sequence. CONCLUSION: The addition of a second burst pacing attempt increases the effectiveness of ATP for FVT and, therefore, reduces the need for high-energy shocks. PMID- 24215375 TI - The physiologist Ewald Hering (1834-1918): curriculum vitae. PMID- 24215376 TI - Second isirv antiviral group conference: overview. PMID- 24215377 TI - Ventilatory strategies and supportive care in acute respiratory distress syndrome. AB - While antiviral therapy is an important component of care in patients with the acute respiratory distress syndrome (ARDS) following influenza infection, it is not sufficient to ensure good outcomes, and additional measures are usually necessary. Patients usually receive high levels of supplemental oxygen to counteract the hypoxemia resulting from severe gas exchange abnormalities. Many patients also receive invasive mechanical ventilation for support for oxygenation, while in resource-poor settings, supplemental oxygen via face mask may be the only available intervention. Patients with ARDS receiving mechanical ventilation should receive lung-protective ventilation, whereby tidal volume is decreased to 6 ml/kg of their predicted weight and distending pressures are maintained <= 30 cm H2 O, as well as increased inspired oxygen concentrations and positive end-expiratory pressure (PEEP) to prevent atelectasis and support oxygenation. While these measures are sufficient in most patients, a minority develop refractory hypoxemia and may receive additional therapies, including prone positioning, inhaled vasodilators, extracorporeal membrane oxygenation, recruitment maneuvers followed by high PEEP, and neuromuscular blockade, although recent data suggest that this last option may be warranted earlier in the clinical course before development of refractory hypoxemia. Application of these "rescue strategies" is complicated by the lack of guidance in the literature regarding implementation. While much attention is devoted to these strategies, clinicians must not lose sight of simple interventions that affect patient outcomes including head of bed elevation, prophylaxis against venous thromboembolism and gastrointestinal bleeding, judicious use of fluids in the post-resuscitative phase, and a protocol-based approach to sedation and spontaneous breathing trials. PMID- 24215378 TI - Detection and management of antiviral resistance for influenza viruses. AB - Neuraminidase inhibitors (NAIs) are first-line agents for the treatment and prevention of influenza virus infections. As for other antivirals, the development of resistance to NAIs has become an important concern particularly in the case of A(H1N1) viruses and oseltamivir. The most frequently reported change conferring oseltamivir resistance in that viral context is the H275Y neuraminidase mutation (N1 numbering). Recent studies have shown that, in the presence of the appropriate permissive mutations, the H275Y variant can retain virulence and transmissibility in some viral backgrounds. Most oseltamivir resistant influenza A virus infections can be managed with the use of inhaled or intravenous zanamivir, another NAI. New NAI compounds and non-neuraminidase agents as well as combination therapies are currently in clinical evaluation for the treatment for severe influenza infections. PMID- 24215380 TI - Advances in antivirals for non-influenza respiratory virus infections. AB - Progress in the development of antivirals for non-influenza respiratory viruses has been slow with the result that many unmet medical needs and few approved agents currently exist. This commentary selectively reviews examples of where specific agents have provided promising clinical benefits in selected target populations and also considers potential therapeutics for emerging threats like the SARS and Middle East respiratory syndrome coronaviruses. Recent studies have provided encouraging results in treating respiratory syncytial virus infections in lung transplant recipients, serious parainfluenza virus and adenovirus infections in immunocompromised hosts, and rhinovirus colds in outpatient asthmatics. While additional studies are needed to confirm the efficacy and safety of the specific agents tested, these observations offer the opportunity to expand therapeutic studies to other patient populations. PMID- 24215381 TI - Influenza vaccines: an Asia-Pacific perspective. AB - This article provides an overview of some aspects of seasonal, pre-pandemic and pandemic influenza vaccines and initiatives aimed to increase influenza vaccine use within the Asia-Pacific region. Expanding the use of influenza vaccines in the Asia-Pacific region faces many challenges. Despite the recent regional history for the emergence of novel viruses, SARS, the H5N1 and H7N9, and the generation of and global seeding of seasonal influenza viruses and initiatives by WHO and other organisations to expand influenza awareness, the use of seasonal influenza vaccines remains low. The improvement in current vaccine technologies with the licensing of quadrivalent, live-attenuated, cell culture-based, adjuvanted and the first recombinant influenza vaccine is an important step. The development of novel influenza vaccines able to provide improved protection and with improved manufacturing capacity is also advancing rapidly. However, of ongoing concern are seasonal influenza impact and the low use of seasonal influenza vaccines in the Asia-Pacific region. Improved influenza control strategies and their implementation in the region are needed. Initiatives by the World Health Organization (WHO), and specifically the Western Pacific Regional Office of WHO, are focusing on consistent vaccine policies and guidelines in countries in the region. The Asian-Pacific Alliance for the Control of Influenza (APACI) is contributing through the coordination of influenza advocacy initiates. PMID- 24215379 TI - Viral-bacterial interactions-therapeutic implications. AB - Viral and bacterial respiratory tract infections are a leading cause of morbidity and mortality worldwide, despite the development of vaccines and potent antibiotics. Frequently, viruses and bacteria can co-infect the same host, resulting in heightened pathology and severity of illness compared to single infections. Bacterial superinfections have been a significant cause of death during every influenza pandemic, including the 2009 H1N1 pandemic. This review will analyze the epidemiology and global impact of viral and bacterial co infections of the respiratory tract, with an emphasis on bacterial infections following influenza. We will next examine the mechanisms by which viral infections enhance the acquisition and severity of bacterial infections. Finally, we will discuss current management strategies for diagnosing and treating patients with suspected or confirmed viral-bacterial infections of the respiratory tract. Further investigation into the interactions between viral and bacterial infections is necessary for developing new therapeutic approaches aimed at mitigating the severity of co-infections. PMID- 24215382 TI - Adjunctive therapies and immunomodulating agents for severe influenza. AB - The value of adjunctive immunomodulatory therapies in treating severe influenza and other respiratory viral infections remains uncertain. Although often used, systemic corticosteroids may increase the risk of mortality and morbidity (e.g. secondary infections) in severe influenza and other viral infections, especially if there is delay or lack of effective antiviral therapy. Non-randomized studies suggest that convalescent plasma appears useful as add-on therapy for patients with severe acute respiratory syndrome, avian influenza A(H5N1), and influenza A (H1N1) 2009 pandemic [A(H1N1)pdm09), but it is limited by its availability. A recent randomized controlled trial (RCT) comparing hyperimmune globulin prepared from convalescent plasma against normal intravenous gammaglobulin (IVIG) manufactured before 2009 as control in patients with severe A(H1N1)pdm09 infection on standard antiviral treatment has shown that the hyperimmune globulin group who received treatment within 5 days of symptom onset had a lower viral load and reduced mortality compared with the controls. A number of agents with immunomodulatory effects (e.g. acute use of statins, N-acetylcysteine, macrolides, PPAR agonists, IVIG, celecoxib, mesalazine) have been proposed for influenza management. However, more animal and detailed human observational studies and preferably RCTs controlling for the effects of antiviral therapy and disease severity are needed for evaluating these agents. The role of plasmapheresis and hemoperfusion as rescue therapy also merits more investigation. PMID- 24215383 TI - Influenza prevention and treatment in transplant recipients and immunocompromised hosts. AB - The host immune response is critical for the control and clearance of influenza virus after initial infection. Unfortunately, key components of the innate and adaptive responses to influenza are compromised in solid organ and hematopoietic stem cell transplant recipients. As a result, influenza in these key patient populations is associated with prolonged viral shedding, more frequent complications, including bacterial and fungal superinfections and rejection, and increased mortality. While vaccine is the critical prophylaxis strategy in other populations, response rates are diminished, particularly early post-transplant, among immunocompromised patients. Prospective data suggest that antiviral prophylaxis represents an effective and safe alternative to vaccine in patients who would be predicted to have poor responses to influenza vaccine. While there have not been randomized, controlled studies of antiviral therapy completed in solid organ or hematopoietic stem cell patient populations, observational data suggest that early therapy is associated with reduced rates of progression to lower airway involvement, morbidity, and mortality. Further studies are needed to define the optimal regimen, dose, duration, and endpoint to define successful treatment. PMID- 24215384 TI - Influenza encephalopathy and related neuropsychiatric syndromes. AB - Influenza is occasionally complicated by CNS disorders, in particular impairment of consciousness. Severe disorders encompass multiple, distinct syndromes manifesting acute encephalopathy, whereas mild disorders represent multiple, ill defined neuropsychiatric syndromes. Acute encephalopathy is manifested with seizures and coma, with or without multi-organ involvement. The outcome varies from death or neurologic sequelae to recovery and differs among syndromes. Transient neuropsychiatric disorders are manifested with delirium and/or abnormal behavior. There also are multiple syndromes. The outcome is usually favorable, although occasional fatal accidents warrant caution. PMID- 24215385 TI - Antivirals in the 2009 pandemic--lessons and implications for future strategies. AB - The World Health Organization's declaration of an imminent swine-origin influenza A pandemic in April 2009 triggered the global launch of national pandemic preparedness plans. An integral component of pandemic preparedness in many countries was the targeted use of antiviral therapy for containment, disease mitigation, and treatment. The 2009 pandemic marked the first pandemic during which influenza antivirals were available for global use. Although most national pandemic plans included provisions for antiviral treatment, these pre-determined protocols required frequent updating as more information became available about the virus, and its susceptibility to antiviral agents, the epidemiology of infection, and the population groups that were most susceptible to severe disease. National public health agencies in countries with both plans for use of antivirals and pre-existing stockpiles, including those in Japan, the United Kingdom, and the United States, operated distinctly different antiviral distribution and treatment programs from one another. In the 3 years following the pandemic, there is still little comparison of the diversity of national antiviral treatment policies and drug distribution mechanisms that were implemented, whether they had any mitigating effects and which might be most efficient. The purpose of this study is to outline roles of antiviral medicines in a pandemic period, provide insights into the diversity of antiviral treatment and distribution policies applied by selected countries between April 2009-July 2010, and to stimulate discussion on whether these policies remain appropriate for implementation in future pandemics. PMID- 24215386 TI - Effects of changes in lunch-time competitive foods, nutrition practices, and nutrition policies on low-income middle-school children's diets. AB - BACKGROUND: The School Nutrition Advances Kids project tested the effectiveness of school-initiated and state-recommended school nutrition practice and policy changes on student dietary intake in low-income middle schools. METHODS: Schools recruited by an application for grant funding were randomly assigned to (1) complete an assessment of nutrition education, policies, and environments using the Healthy School Action Tools (HSAT) and implement an action plan, (2) complete the HSAT, implement an action plan, and convene a student nutrition action team, (3) complete the HSAT and implement an action plan and a Michigan State Board of Education nutrition policy in their cafeteria a la carte, or (4) a control group. All intervention schools were provided with funding and assistance to make self selected nutrition practice, policy, or education changes. Block Youth Food Frequency Questionnaires were completed by 1176 seventh-grade students from 55 schools at baseline and during eighth-grade follow-up. Nutrient density and food group changes for the intervention groups were compared to the control group, controlling for baseline dietary intake values, gender, race/ethnicity, school kitchen type, urbanization, and percent of students eligible for free or reduced price meals. Analyses were conducted by randomization and based on changes the schools self-selected. RESULTS: Improvements in students' nutrient density and food group intake were found when schools implemented at least three new nutrition practice changes and established at least three new nutrition policies. Students in schools that introduced mostly healthful foods in competitive venues at lunch demonstrated the most dietary improvements. CONCLUSIONS: New USDA nutrition standards for a la carte and vending will likely increase the healthfulness of middle school children's diets. PMID- 24215387 TI - Impaired decision making on the Balloon Analogue Risk Task as a result of long term alcohol use. AB - The Balloon Analogue Risk Task (BART) is an experimental measure of risk taking that has commonly been employed to measure the risk taking behavior of nonclinical populations. Previous research has indicated that the task measures a unique aspect of behavioral disinhibition, but there has not as yet been focus upon the possible impact of other aspects of cognitive processing on performance. The current study investigated the cognitive factors related to performance of the BART in an alcohol-using sample. Seventeen individuals with long-term alcohol use were matched for age and education to a group of 17 nonusing participants. The results indicated that the alcohol-using group pumped the balloons on the BART to a lesser extent than did the nonusing group across all trials on the task. The results indicate that the alcohol-using group made less "optimal" decisions on the BART most notably due to neuropsychological impairment in the domains of immediate memory and executive functioning. PMID- 24215389 TI - The comparison of density-elastic modulus equations for the distal ulna at multiple forearm positions: a finite element study. AB - The accuracy of an empirically derived density-modulus equation for bone depends upon the loading conditions and anatomic site of bone specimens used for experimentation. A recent study used FE modeling to compare the ability of three density-modulus relationships to predict strain during bending in neutral forearm rotation in the distal ulna; however, due to the inhomogeneous nature of these FE models, the performance of each equation is not necessarily consistent throughout forearm rotation. This issue is addressed in the present study, which compares the performance of these equations in pronation and supination. Strain gauge data were collected at six discreet locations of six ulna specimens loaded in bending at 40 degrees of pronation and supination. Three FE models of each specimen were made, one for each density-modulus relation, and the strain output compared to the experimental data. The equation previously shown to be most accurate in predicting ulnar strain in neutral forearm rotation was also most accurate in pronation and supination. These results identify this one equation as the most appropriate for future FE analysis of the ulna (including adaptive remodeling, and further show that isotropic and inhomogeneous FE bone models may provide consistent results in different planes of bending. PMID- 24215388 TI - A randomized clinical trial comparing 4-port, 3-port, and single-incision laparoscopic cholecystectomy. AB - BACKGROUNDS: Despite increasing trend in single incision laparoscopic cholecystectomy (SILC), there is still controversy regarding its global acceptance as a routine practice. Our study aimed to compare surgical events, early in-hospital and later outcomes of SILC with conventional multiport laparoscopic cholecystectomy (LC). METHODS: Through a randomized controlled trial (RCT) between June and December 2011, 90 consecutive patients with documented biliary diseases waiting for LC were equally allocated to 3-port, 4-port, and single incision LC group. Operative time, surgical adverse events, postoperative pain according to visual analogue scale (VAS), total morphine administration, length of hospital stay, and cosmetic outcomes were compared between these three groups. RESULTS: A total of 27 males (30%) and 63 females (70%) were enrolled in this study. The average patients' age and BMI were 42.6 +/- 12.1 years and 26.2 +/- 2.7 kg/m(2), respectively. Operative time in SILC group was significantly longer than other groups. Total intraoperative adverse events and postoperative complications did not differ significantly between the three groups. Mean +/- SD VAS score at rest was significantly lower (p < 0.05) in SILC group. The average VAS at coughing was significantly lower in SILC group in all time intervals except the first 6 hr (p < 0.05). In addition, total morphine dose showed significantly lower amount in SILC group (p = 0.02). 12-month follow-up did not reveal significant difference between the study groups (p > 0.05). CONCLUSION: SILC is associated with less postoperative pain in later hours, reduces in hospital analgesic dosages, has longer procedure time, but does not increase intraoperative and postoperative adverse events It seems that SILC has no obvious advantages in terms of later outcomes. PMID- 24215390 TI - Combined diffraction and density functional theory calculations of halogen-bonded cocrystal monolayers. AB - This work describes the combined use of synchrotron X-ray diffraction and density functional theory (DFT) calculations to understand the cocrystal formation or phase separation in 2D monolayers capable of halogen bonding. The solid monolayer structure of 1,4-diiodobenzene (DIB) has been determined by X-ray synchrotron diffraction. The mixing behavior of DIB with 4,4'-bipyridyl (BPY) has also been studied and interestingly is found to phase-separate rather than form a cocrystal, as observed in the bulk. DFT calculations are used to establish the underlying origin of this interesting behavior. The DFT calculations are demonstrated to agree well with the recently proposed monolayer structure for the cocrystal of BPY and 1,4-diiodotetrafluorobenzene (DITFB) (the perfluorinated analogue of DIB), where halogen bonding has also been identified by diffraction. Here we have calculated an estimate of the halogen bond strength by DFT calculations for the DITFB/BPY cocrystal monolayer, which is found to be ~20 kJ/mol. Computationally, we find that the nonfluorinated DIB and BPY are not expected to form a halogen-bonded cocrystal in a 2D layer; for this pair of species, phase separation of the components is calculated to be lower energy, in good agreement with the diffraction results. PMID- 24215391 TI - Species versus guild level differentiation revealed across the annual cycle by isotopic niche examination. AB - Interspecific competitive interactions typically result in niche differentiation to alleviate competition through mechanisms including character displacement. However, competition is not the sole constraint on resource partitioning, and its effects are mediated by factors including the environmental context in which species coexist. Colonial seabirds provide an excellent opportunity to investigate the importance of competition in shaping realized niche widths because their life histories lead to variation in intra- and interspecific competition across the annual cycle. Dense breeding aggregations result in intense competition for prey in surrounding waters, whereas non-breeding dispersal to larger geographical areas produces lower densities of competitors. Bayesian hierarchical models of the isotopic niche, closely aligned to the trophic niche, reveal the degree of segregation between species and functional groups during both time periods. Surprisingly, species explained far more of the variance in the isotopic niche during the non-breeding than the breeding period. Our results underline the key role of non-breeding dynamics in alleviating competition and promoting distinctions between species through the facilitation of resource partitioning. Such situations may be common in a diverse range of communities sustained by ephemeral but abundant food items. This highlights how consideration of the hierarchical grouping of competitive interactions alongside consideration of abiotic constraints across the complete annual cycle allows a full understanding of the role of competition in driving patterns of character displacement. PMID- 24215392 TI - Response to comment by Rabilloud on "Prevented mortality and greenhouse gas emissions from historical and projected nuclear power". PMID- 24215393 TI - Analytical methods in lipidomics and their applications. PMID- 24215394 TI - Implicit transfer of reversed temporal structure in visuomotor sequence learning. AB - Some spatio-temporal structures are easier to transfer implicitly in sequential learning. In this study, we investigated whether the consistent reversal of triads of learned components would support the implicit transfer of their temporal structure in visuomotor sequence learning. A triad comprised three sequential button presses ([1][2][3]) and seven consecutive triads comprised a sequence. Participants learned sequences by trial and error, until they could complete it 20 times without error. Then, they learned another sequence, in which each triad was reversed ([3][2][1]), partially reversed ([2][1][3]), or switched so as not to overlap with the other conditions ([2][3][1] or [3][1][2]). Even when the participants did not notice the alternation rule, the consistent reversal of the temporal structure of each triad led to better implicit transfer; this was confirmed in a subsequent experiment. These results suggest that the implicit transfer of the temporal structure of a learned sequence can be influenced by both the structure and consistency of the change. PMID- 24215395 TI - TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population. AB - PURPOSE: High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth beta induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. METHODS: Cases with high myopia with a spherical equivalent of >=-6 diopters (D) and emmetropic controls with spherical equivalent within +/-0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using chi(2) or Fisher's exact test. RESULTS: Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p < 0.05) association with the disease phenotype. Since the variant allele frequency of both the single-nucleotide polymorphisms in cases is higher than controls with odds ratio greater than 1.Therefore, variant allele of both the single-nucleotide polymorphisms represents the possible risk factor for myopia in the Kashmiri population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. CONCLUSIONS: TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia. PMID- 24215396 TI - Bias-dependent molecular-level structure of electrical double layer in ionic liquid on graphite. AB - Here we report the bias-evolution of the electrical double layer structure of an ionic liquid on highly ordered pyrolytic graphite measured by atomic force microscopy. We observe reconfiguration under applied bias and the orientational transitions in the Stern layer. The synergy between molecular dynamics simulation and experiment provides a comprehensive picture of structural phenomena and long and short-range interactions, which improves our understanding of the mechanism of charge storage on a molecular level. PMID- 24215397 TI - Five new stilbene glycosides from the roots of Polygonum multiflorum. AB - Five new stilbene glycosides (1-5), together with six known ones, were isolated from the roots of Polygonum multiflorum. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. PMID- 24215398 TI - Sorbicillamines A-E, nitrogen-containing sorbicillinoids from the deep-sea derived fungus Penicillium sp. F23-2. AB - Five new nitrogen-containing sorbicillinoids named sorbicillamines A-E (1-5) were isolated from an agitated culture of the deep-sea-derived fungus Penicillium sp. F23-2, which has previously produced indole alkaloids and terpenoids when cultured under static conditions. The structures of 1 to 5, including absolute configurations, were determined based on MS, NMR, and circular dichroism (CD) data. The cytotoxicities of the five new sorbicillin alkaloids against the HeLa, BEL-7402, HEK-293, HCT-116, and P388 cell lines were evaluated. PMID- 24215399 TI - Coreceptor tropism determined by genotypic assay in HIV-1 circulating in Thailand, where CRF01_AE predominates. AB - OBJECTIVES: Chemokine (C-C motif) receptor 5 (CCR5) inhibitors are a novel class of antiretroviral agents that are promising for treatment of patients who harbour the HIV-1 R5 strain. Data on coreceptor tropism in non-B HIV-1 subtypes are limited. We studied coreceptor tropism in HIV-1 circulating in Thailand, where CRF01_AE predominates, using a genotypic assay. METHODS: We compiled V3 sequences of HIV-1 strains circulating in Thailand during 2010-2012. Coreceptor tropism was predicted based on V3 sequences using geno2pheno version 2.5 (http://coreceptor.bioinf.mpi-inf.mpg.de). RESULTS: One hundred and fifty-five HIV-1-infected patients were enrolled in this study. Ninety-nine patients (63.9%) were antiretroviral-naive, and the remainder had virological failure. The median (interquartile range) CD4 cell count and HIV-1 RNA were 220 (74-379) cells/MUL and 75,374 (14,127-226,686) HIV-1 RNA copies/mL, respectively. Of the sequences obtained from these patients, 119 (76.8%) were CRF01_AE and 22 (14.2%) were subtype B. At a false positive rate of < 5%, 61 (39.4%) HIV-1-infected individuals were predicted to harbour the X4 phenotype. X4 viruses were detected more frequently in the treatment-failure group compared with the treatment-naive group (30.3 vs. 55.4%, respectively; P = 0.002). Those with CRF01_AE had a higher proportion of X4 viruses compared with non-AE subtypes (47.9 vs. 11.1%, respectively; P < 0.001). By multivariate logistic regression, CRF01_AE and treatment failure were independently associated with predicted X4 phenotype [odds ratio (OR) 7.93; 95% confidence interval (CI) 2.57-24.50; P < 0.001, and OR 3.10; 95% CI 1.50-6.42; P = 0.002, respectively]. CONCLUSIONS: CRF01_AE and treatment failure are associated with the predicted X4 phenotype. In regions where CRF01_AE predominates, use of CCR5 inhibitors must be considered with caution. The phenotypic assay and its correlation with genotypes should be further investigated in CRF01_AE. PMID- 24215400 TI - Noninnocent counterion effect on the rearrangements of cationic intermediates in a gold(I)-catalyzed alkenylsilylation reaction. AB - A mechanistic DFT study of the gold(I)-catalyzed alkenylsilylation reaction of a silyl-tethered 1,6-enyne system is reported. A novel pathway involving bistriflimide counterion-assisted rearrangements of carbocation and silyl cation intermediates corroborates the experimental observations. The results suggest the important role of the counterion in modulating the reactivity of cationic intermediates in gold catalysis. PMID- 24215401 TI - Corruption, inequality and population perception of healthcare quality in Europe. AB - BACKGROUND: Evaluating the quality of healthcare and patient safety using general population questionnaires is important from research and policy perspective. Using a special wave of the Eurobarometer survey, we analysed the general population's perception of health care quality and patient safety in a cross country setting. METHODS: We used ordered probit, ordinary least squares and probit analysis to estimate the determinants of health care quality, and ordered logit analysis to analyse the likelihood of being harmed by a specific medical procedure. The models used population weights as well as country-clustered standard errors. RESULTS: We found robust evidence for the impact of socio demographic variables on the perception of quality of health care. More specifically, we found a non-linear impact of age on the perception of quality of health care and patient safety, as well as a negative impact of poverty on both perception of quality and patient safety. We also found robust evidence that countries with higher corruption levels were associated with worse perceptions of quality of health care. Finally, we found evidence that income inequality affects patients' perception vis-a-vis safety, thus feeding into the poverty/health care quality nexus. CONCLUSIONS: Socio-demographic factors and two macro variables (corruption and income inequality) explain the perception of quality of health care and likelihood of being harmed by adverse events. The results carry significant policy weight and could explain why targeting only the health care sector (without an overall reform of the public sector) could potentially be challenging. PMID- 24215402 TI - Increased leptin and A-FABP levels in relapsing and progressive forms of MS. AB - BACKGROUND: Leptin and adipocyte-fatty acid binding protein (A-FABP) are produced by white adipose tissue and may play a role in chronic inflammation in Multiple Sclerosis (MS). To assess leptin and A-FABP in relapsing and progressive forms of MS. METHODS: Adipokine levels were measured in untreated adult relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and Healthy control (HC). Pediatric-onset MS (POMS) and pediatric healthy controls (PHC) were also assessed. Leptin and A-FABP levels were measured in serum by ELISA. Groups were compared using linear mixed-effects model. RESULTS: Excluding two patients with Body Mass Index (BMI) > 50, a significant difference in leptin level was found between RRMS and HC controlling for age (p = 0.007), SPMS and HC controlling for age alone (p = 0.002), or age and BMI (p = 0.007). A FABP levels were higher in SPMS than HC (p = 0.007), controlling for age and BMI. Differences in A-FABP levels between POMS and PHC was observed after controlling for age (p = 0.019), but not when BMI was added to the model (p = 0.081). CONCLUSION: Leptin and A-FABP levels are highest in SPMS compared to HC, suggesting a role in pathogenesis of this disease subtype. A-FABP levels are increased in POMS patients and may play a role in the early stages of disease. PMID- 24215403 TI - The clinical potential for koff-rate measurement in adoptive immunotherapy. PMID- 24215404 TI - Do Tregitopes have the potential to impact the current treatment landscape of autoimmune diseases? PMID- 24215406 TI - Certolizumab pegol in axial spondyloarthritis. AB - The axial spondyloarthritis (SpA) classification criteria cover both patients with ankylosing spondylitis and non-radiographic axial SpA. After failure of NSAIDs TNF-alpha-inhibitors (TNF-blockers) can be given to patients with active axial SpA. Until recently, the TNF-blockers infliximab, adalimumab, etanercept and golimumab are labeled for the treatment of active ankylosing spondylitis while for active nr-axSpA only adalimumab has been approved in Europe. The TNF blocker certolizumab pegol has recently been evaluated in the RAPID-axSpA trial which is the first placebo-controlled randomized-controlled trial in the entire group of axial SpA. An elevated C-reactive protein and/ or evidence of bone marrow edema on MRI of the sacroiliac joints were required for inclusion in RAPID axSpA, and patients could have been preexposed to TNF-blockers. The interesting data of this important trial in the context of the emerging therapeutic field of non-radiographic axial SpA therapy is discussed in this review. PMID- 24215407 TI - Predictors of progression to Type 1 diabetes: preparing for immune interventions in the preclinical disease phase. AB - Type 1 diabetes is an incurable disease associated with risk of serious acute and chronic complications. It is caused by a marked loss in insulin-producing beta cells. Immune intervention at clinical onset can transiently suppress a further decline in residual functional beta cell mass, particularly in young patients with a higher residual insulin producing capacity at start of treatment. It might achieve a higher effect during the preclinical phase when the beta cell mass is not yet severely affected. Such prevention trials can be prepared by identifying individuals at very high risk to develop diabetes within 3 years and presenting signs of declining, yet relatively preserved, functional beta cell mass. This article reviews biomarker screening strategies to select these participants and discusses developments that can facilitate rapid and straightforward conclusions from novel clinical studies. PMID- 24215408 TI - The case for measuring antibodies to specific citrullinated antigens. AB - Anti-citrullinated protein/peptide antibodies (ACPA) are the principal autoantibody system associated with rheumatoid arthritis (RA), with diagnostic sensitivity of 70% and specificity of 95%. Current testing for ACPA uses the anti cyclic citrullinated peptide assay (anti-CCP) which measures a generalized reactivity with citrulline-containing peptides, thus giving no insight into reactivity to specific RA antigens. Of these, the best characterized are, alpha enolase, fibrinogen/fibrin, vimentin, Type 2 collagen and filaggrin, antibodies to each of which are found in approximately 30-60% of RA cases. Given reports of cross-reactivity between citrullinated antigens, we discuss whether or not measuring these specific antibodies could aid: clinical diagnosis, identification of clinical subsets and drug responses, or provide insight into pathogenic mechanisms or etiology of RA. PMID- 24215409 TI - Accelerated telomere shortening in rheumatic diseases: cause or consequence? AB - Accelerated aging of the immune system (immune aging), represented by telomere shortening, has been implicated in a variety of rheumatic diseases. Studies addressing telomere shortening in rheumatic diseases so far yielded controversial results. The current review aims to provide an overview on the role of immune aging in a plethora of immune-mediated conditions including systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis. The main question this review aims to answer is whether rheumatic diseases cause accelerated aging or that accelerated aging drives rheumatic diseases. PMID- 24215410 TI - Agammaglobulinemia: causative mutations and their implications for novel therapies. AB - Agammaglobulinemias are primary (inherited) immunodeficiencies characterized by the lack of functional B-cells and antibodies, and are caused by mutations in genes encoding components of the pre-B-cell or B-cell receptor, or their signaling pathways. The known genetic defects do not account for all agammaglobulinemic patients, suggesting that novel mutations underlying the disease remain to be found. While efficient, the current life-maintaining therapy with immunoglobulins and antibiotics is non-curative, prompting research into alternative treatment strategies that aim at rescuing the expression of the affected protein, thus giving rise to functional B-cells. These include gene therapy, which could be used to correct the defective gene or replace it with a functional copy. For a number of genetic defects, another alternative is to modulate the splicing of the affected transcripts. While these technologies are not yet ready for clinical trials in agammaglobulinemia, advances in genomic targeting are likely to make this option viable in the near future. PMID- 24215411 TI - Advances in our understanding of the pathogenesis of Henoch-Schonlein purpura and the implications for improving its diagnosis. AB - Henoch-Schonlein purpura (HSP) is a leukocytoclastic vasculitis classically characterized by palpable purpura, arthritis, abdominal pain and renal disease. In this article, we summarize our current understanding of the pathogenesis of HSP and the implications for improving its diagnosis. Although the pathogenesis of HSP is not fully understood yet, exciting new information has emerged in recent years, leading to a better understanding of its pathogenesis. Here, we discuss genetic predisposition, immunoglobulins with a particular emphasis on IgA1, activated complements, cytokines and chemokines, abnormal coagulation and autoantibodies in the underlying pathogenic mechanisms. Finally, diagnostic criteria for HSP developed by institutions such as the American College of Rheumatology and the European League against Rheumatism/Paediatric Rheumatology European Society were proposed to improve early detection and diagnosis. PMID- 24215412 TI - Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning. AB - Altered neonatal Toll-like receptor (TLR) function is hypothesized to contribute to the heightened susceptibility to infection and perpetuated inflammation in term and preterm neonates, clinically evident in neonatal sepsis and increased rates of inflammatory disorders. Current data indicate that basal TLR expression in term neonates equals adult expression patterns, while expression in preterm infants seems to increase, depending on gestational age. Regarding TLR signaling, some studies suggest TLR incompetence in neonates associated with impaired pro inflammatory responses, others describe neonatal TLR function well developed and allude to its hyper-inflammation tendency. We discuss the competing positions and considerable limitations of research approaches and conclude that neonatal innate immunity is not generally less able to respond to TLR stimulation. Moreover, we describe pre-conditioning factors other than immaturity having a comparable impact. In the long term, better understanding of the complex interplay of pre- and postnatal conditions and maturation-dependent neonatal TLR function may provide new therapeutic approaches. PMID- 24215413 TI - The impact of breastfeeding on lung development and function: a systematic review. AB - With the global trend of increasing asthma and allergic disorders there is strong interest regarding early life nutrition as a potentially modifiable risk factor for lung disease. This systematic review includes 10 studies that assessed the effect of breastfeeding on lung growth and function. The review found breastfeeding to be beneficial for lung function, with the most consistent effect on increased forced vital capacity. There was no clear evidence that the relationship between breastfeeding and lung function was mediated through other factors. Furthermore, the findings from the few studies that investigated if maternal asthma modified the effect of breastfeeding on lung function were inconsistent. Further research is needed to determine the specific details such as duration and type (exclusive vs partial) of breastfeeding that leads to improved lung function. PMID- 24215414 TI - Prevention of asthma: where are we in the 21st century? AB - Asthma is the most common chronic disease of childhood and, in the latter part of the 20th century, reached epidemic proportions. Asthma is generally believed to result from gene-environment interactions. There is consensus that a 'window of opportunity' exists during pregnancy and early in life when environmental factors may influence its development. We review multiple environmental, biologic and sociologic factors that may be important in the development of asthma. Meta analyses of studies have demonstrated that multifaceted interventions are required in order to develop asthma prevention. Multifaceted allergen reduction studies have shown clinical benefits. Asthma represents a dysfunctional interaction with our genes and the environment to which they are exposed, especially in fetal and early infant life. The increasing prevalence of asthma also may be an indication of increased population risk for the development of other chronic non-communicable autoimmune diseases. This review will focus on the factors which may be important in the primary prevention of asthma. Better understanding of the complex gene-environment interactions involved in the development of asthma will provide insight into personalized interventions for asthma prevention. PMID- 24215415 TI - Prediction of hypersensitivity to antibiotics: what factors need to be considered? AB - This review focuses on the epidemiology and different risk factors related to the development of hypersensitivity reactions to antibiotics, with a focus on betalactams and fluoroquinolones, the compounds most frequently involved in these reactions, due to their high level of consumption. The true prevalence of allergic drug reactions is unknown and the corresponding morbidity, mortality and associated economic costs are often underestimated. It is reported that multiple risk factors, related to both the drug and the patient, can modify the clinical expression of immune-mediated drug reactions. These include the chemical properties, molecular weight and administration route of the drug and the age, gender, concomitant diseases and genetic factors of the patient. PMID- 24215416 TI - Celiac disease and endocrine autoimmune disorders in children: an update. AB - Celiac disease (CD) is a life-long inflammatory condition of the gut that occurs in genetically susceptible individuals. Several autoimmune diseases (AI) are associated with CD. To date, no conclusive evidence is available that proves if the relationship between CD and AI is mediated by gluten exposure, or if CD and AI could co-occur due to other causes, in particular the loss of the intestinal barrier function and the common genetic background. Furthermore, it is not clear yet if CD needs a regular screening program for AI. This review will cover the key studies on both the pathogenetic and clinical evidence explaining this association. We will review the reports including patients aged <18 years with CD and endocrine AI. PMID- 24215417 TI - Optimizing the use of regulatory T cells in allotransplantation: recent advances and future perspectives. AB - Apart from clonal deletion of self-reactive T cells in the thymus, Tregs are the major regulators of immune responses in the periphery and maintain a state of self-tolerance free from autoimmune diseases. Due to their inherent suppressive function, Tregs are being explored for their therapeutic potential in preventing autoimmunity and improving survival of allografts. This review provides recent updates on Treg biology and their use in animal as well as clinical models of transplantation. We discuss potential problems that limit the widespread clinical application of Tregs and provide future perspectives on how to optimize their medical use. Special consideration is given to methods by which Tregs should be isolated and expanded in order to facilitate clinical therapies. We also focus on recent discussions of Treg stability and plasticity, with specific insights into preventing the loss of Treg suppression by allotransplant-mediated inflammation. PMID- 24215418 TI - Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system. AB - Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6 hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-alpha) plasma levels were unchanged and inhibition of TNF-alpha had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events. PMID- 24215419 TI - The relationship between paroxysmal atrial fibrillation and coronary artery spasm. AB - BACKGROUND: Coronary artery spasm has recently been reported as a complication of the ablation of atrial fibrillation (AF). It may be induced by cardiac autonomic nervous dysfunction during radiofrequency catheter ablation of AF. However, the underlying mechanism is not clear. We hypothesized that patients with paroxysmal AF coincidentally exhibit coronary artery spasm. METHODS: A total of 51 patients were enrolled in a case control study to clarify the relationship between paroxysmal AF and coronary artery spasm. We evaluated 17 patients with paroxysmal AF (AF group) and 34 patients without paroxysmal AF (control group). Drug-induced coronary artery spasm provocation tests were performed by intracoronary administration of acetylcholine or ergonovine. RESULTS: The AF group consisted of nine males and eight females, mean age 67 +/- 10 years. The control group consisted of 16 males and 18 females, mean age 60 +/- 14 years. In the AF group, coronary artery spasm was induced in 13 patients (76.5%) before AF ablation. In the control group, coronary artery spasm was induced in three patients (8.8%). Coronary artery spasm was more frequently induced in patients with AF (76.5% vs 8.8%; odds ratio, 33.583; 95% confidence interval, 6.5732-171.58; P < 0.0001). In the AF group, ventricular fibrillation and AF were recorded immediately after right coronary artery spasm induction in one patient. CONCLUSIONS: Paroxysmal AF patients have high positive rates of drug-provoked coronary artery spasm. Patients with paroxysmal AF may coincidentally exhibit coronary artery spasm. PMID- 24215420 TI - The assessment of pulsed dye laser treatment of port-wine stains with reflectance confocal microscopy. AB - BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive technique for evaluating cutaneous lesions with cellular level resolution close to conventional histopathology. The aim of this study is to observe the vascular changes in Port wine (PWS) lesions and assess the clinical efficacy of Pulsed Dye Laser (PDL) treatment by examining vessel diameter and density with RCM. MATERIALS AND METHODS: Eleven adult patients with PWS, each had four test patches carried out with different pulse durations (1.5, 3, 6, and 10 ms), respectively; fluences of 9-12 J/cm2; and a spot size of 7 mm. The PDL treatment was repeated 3-5 times at a 2-month interval. Photographs and measurements with RCM were taken before each treatment and 2 months after the last treatment. RESULTS: The PDL treatment exhibited increasing clearance with reducing pulse durations. Vessel diameters and densities were significantly decreased in the same pulse-duration groups after treatment. There was significant difference between 1.5 ms pulse-duration group and other pulse-duration groups in reducing blood vessel diameter at the depth of 150 MUm. CONCLUSIONS: RCM can be used to assess the clinical efficacy of PDL treatment. PMID- 24215421 TI - The use of infrared radiation in the treatment of skin laxity. AB - BACKGROUND: Cosmetic surgery and medicine are extremely interesting fields for a plastic surgeon. Lasers and lights determine ablation, contraction and regenerating stimulus in skin tissues. The aim of this study is to examine the use of infrared lights in treating facial and body skin laxity. METHODS: Between 2007 and 2011, in the Department of Plastic and Reconstructive Surgery at the Hospital San Camillo-Forlanini, 303 patients were enrolled in the study and underwent laser therapy. The laser operates in wavelength from 1100 to 1800 nm. The treated areas are: face, neck, eyebrows, abdomen, legs and buttocks. RESULTS: We have noticed no systemic complications. A case of a patient with a three days lasting erythema on both lower eyelids caused by laser therapy healed without any pharmacological therapy. Neither hyper- nor hypopigmentation of the skin was found. The satisfaction degree of patients has been: facial, neck and eyebrow lifting "very satisfactory" for 70% of the patients, "satisfactory" for 10%, "unsatisfactory" for 20%; for the other areas it was "very satisfactory" for 40%, "satisfactory" for 20% and "unsatisfactory" for 40%. CONCLUSION: The use of infrared radiation represents a valid alternative to surgical lifting, but cannot replace it. The infrared light technique used has turned out to be useful in contrasting skin laxity of the face and other parts of the body. The absence of scars and surgical risk makes this technique useable for a large number of patients. PMID- 24215422 TI - Fractional Q-switched 1,064-nm laser for the treatment of photoaged-photodamaged skin. AB - INTRODUCTION: The Q-switched 1064-nm laser is associated with rapid vaporization and thermal expansion stresses leading to skin mechanical damage and is typically used for correction of exogenous and endogenous deep pigmentation. Giving the common place of fractional, infrared-domain milliseconds non-ablative lasers in aesthetic dermatology, a novel non-ablative fractional Q-switched 1,064-nm laser was studied for photoaged skin concerns. MATERIALS AND METHODS: Ten healthy female subjects (Age range: 35-53 years, mean: 44.3) and skin types I-IV were diagnosed with mild-to-moderate facial photo-damage, hyper-pigmentation, telangiectasia, laxity, skin roughness, and actinic keratosis. Subjects were treated with a new non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser (Harmony XL, Alma Lasers Ltd.). Treatments consisted of four sessions at 2-4 week intervals. Follow-up (FU) visits were 1 and 3 months following the final treatment. RESULTS: Utilizing the Glogau scale, six Subjects were graded Type II (means wrinkles in motion), and four Subjects were graded Type III (means wrinkles at rest) at Baseline. At the FU2, 3-month post final treatment, 60% of the subjects were graded with at least a one-point improvement in the overall Glogau global assessment. Between baseline and FU2, Investigator assessments showed the following improvements: Hyperpigmentation 70%, Telangiectasias 80%, Laxity 80%, Tactile Roughness 60%, and actinic keratoses 60%. Pain assessment was reported between 0 and 2 in all treatments (scale 0-10). Of expected side effects, erythema was most common, occasionally being reported as high as a 2(scale 0-10). No unexpected adverse effects were reported. CONCLUSION: The non ablative fractional Q-Switched 1,064-nm Nd: YAG laser is safe and effective in improving signs of mild-to-moderate photodamage skin irregularities with no downtime, no pain to only minimal pain, and without any adverse side effects. PMID- 24215423 TI - Biomechanical study of the influence of the weight of equipment on selected trunk muscles. AB - Overexertion and pain of the musculoskeletal system may occur partly owing to load application by the equipment. Both the weight of equipment and the duration of loading are relevant. The aim of the present study was to examine the extent of loading and resultant strain in the trunk muscles. Therefore, the trunk posture of soldiers and muscular activity in reaction to different equipment components (helmet, load-carrying equipment, gun and backpack) were evaluated. Electromyography was performed and a visual assessment of body axis was conducted based on standardised planar images. Data indicate that the activity of the trunk muscles examined (latissimus dorsi, trapezius and pectoralis major) is dependent on the weight and distribution of the equipment components. Activity in the trapezius muscle, for instance, was doubled during specific load application. Moreover, the method of carrying the rifle had a significant influence on the activity of the trapezius muscle (one-sided decrease of activity by 50%). Subjects were able to stabilise the body axis in the coronal plane through increased muscle activity, however, in the sagittal plane a compensatory ventral inclination of the body was observed. Uneven load distribution can lead to an irregular strain on the musculoskeletal system. PMID- 24215424 TI - Smaller splenium in children with nonverbal learning disability compared to controls, high-functioning autism and ADHD. AB - The current study investigated morphological differences in the corpus callosum in children ages 8 to 18 years old with nonverbal learning disability (NLD; n = 19), high-functioning autism (HFA; n = 23), predominantly inattentive ADHD (ADHD:PI; n = 23), and combined type ADHD (ADHD:C; n = 25), as well as those demonstrating typical development (n = 57). Midsagittal area of the corpus callosum and five midsagittal anterior-to-posterior corpus callosum segments were examined using magnetic resonance imaging. Controlling for midsagittal brain area and age, no group differences were found for total corpus callosum area. This finding indicates that higher functioning children on the autistic spectrum do not have smaller corpus callosi as has been found in previous research with heterogeneous samples. Following segmentation of the corpus callosum, the NLD group was observed to have significantly smaller splenia compared to all other groups. Smaller splenia in the NLD group was associated with lower WASI PIQ scores but not WASI VIQ scores. Children with HFA were observed to have larger midbody areas than children with NLD and neurotypically developing children. Children with HFA and NLD demonstrated behavioral symptoms of inattention and hyperactivity similar to the ADHD groups indicating that corpus callosum differences seen in the NLD and HFA groups are not related to these behaviors. PMID- 24215425 TI - Smoking association with influenza infection in renal transplant recipients. AB - We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3-76; P = 0.004). PMID- 24215426 TI - Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy. AB - Taking a nanoparticle (NP) from discovery to clinical translation has been slow compared to small molecules, in part by the lack of systems that enable their precise engineering and rapid optimization. In this work we have developed a microfluidic platform for the rapid, combinatorial synthesis and optimization of NPs. The system takes in a number of NP precursors from which a library of NPs with varying size, surface charge, target ligand density, and drug load is produced in a reproducible manner. We rapidly synthesized 45 different formulations of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) NPs of different size and surface composition and screened and ranked the NPs for their ability to evade macrophage uptake in vitro. Comparison of the results to pharmacokinetic studies in vivo in mice revealed a correlation between in vitro screen and in vivo behavior. Next, we selected NP synthesis parameters that resulted in longer blood half-life and used the microfluidic platform to synthesize targeted NPs with varying targeting ligand density (using a model targeting ligand against cancer cells). We screened NPs in vitro against prostate cancer cells as well as macrophages, identifying one formulation that exhibited high uptake by cancer cells yet similar macrophage uptake compared to nontargeted NPs. In vivo, the selected targeted NPs showed a 3.5-fold increase in tumor accumulation in mice compared to nontargeted NPs. The developed microfluidic platform in this work represents a tool that could potentially accelerate the discovery and clinical translation of NPs. PMID- 24215427 TI - Nanoparticle-protein interactions: a thermodynamic and kinetic study of the adsorption of bovine serum albumin to gold nanoparticle surfaces. AB - Investigating the adsorption process of proteins on nanoparticle surfaces is essential to understand how to control the biological interactions of functionalized nanoparticles. In this work, a library of spherical and rod-shaped gold nanoparticles (GNPs) was used to evaluate the process of protein adsorption to their surfaces. The binding of a model protein (bovine serum albumin, BSA) to GNPs as a function of particle shape, size, and surface charge was investigated. Two independent comparative analytical methods were used to evaluate the adsorption process: steady-state fluorescence quenching titration and affinity capillary electrophoresis (ACE). Although under favorable electrostatic conditions kinetic analysis showed a faster adsorption of BSA to the surface of cationic GNPs, equilibrium binding constant determinations indicated that BSA has a comparable binding affinity to all of the GNPs tested, regardless of surface charge. BSA was even found to adsorb strongly to GNPs with a pegylated/neutral surface. However, these fluorescence titrations suffer from significant interference from the strong light absorption of the GNPs. The BSA-GNP equilibrium binding constants, as determined by the ACE method, were 10(5) times lower than values determined using spectroscopic titrations. While both analytical methods could be suitable to determine the binding constants for protein adsorption to NP surfaces, both methods have limitations that complicate the determination of protein-GNP binding constants. The optical properties of GNPs interfere with Ka determinations by static fluorescence quenching analysis. ACE, in contrast, suffers from material compatibility issues, as positively charged GNPs adhere to the walls of the capillary during analysis. Researchers seeking to determine equilibrium binding constants for protein-GNP interactions should therefore utilize as many orthogonal techniques as possible to study a protein-GNP system. PMID- 24215429 TI - spads 1.0: a toolbox to perform spatial analyses on DNA sequence data sets. AB - SPADS 1.0 (for 'Spatial and Population Analysis of DNA Sequences') is a population genetic toolbox for characterizing genetic variability within and among populations from DNA sequences. In view of the drastic increase in genetic information available through sequencing methods, spads was specifically designed to deal with multilocus data sets of DNA sequences. It computes several summary statistics from populations or groups of populations, performs input file conversions for other population genetic programs and implements locus-by-locus and multilocus versions of two clustering algorithms to study the genetic structure of populations. The toolbox also includes two MATLAB and r functions, GDISPAL and GDIVPAL, to display differentiation and diversity patterns across landscapes. These functions aim to generate interpolating surfaces based on multilocus distance and diversity indices. In the case of multiple loci, such surfaces can represent a useful alternative to multiple pie charts maps traditionally used in phylogeography to represent the spatial distribution of genetic diversity. These coloured surfaces can also be used to compare different data sets or different diversity and/or distance measures estimated on the same data set. PMID- 24215430 TI - Characterization of fullerene-modified silica as a complement to graphite-like phases for use in two-dimensional high performance liquid chromatography. AB - Carbonaceous sorbents have a long and rich history of development and application in all areas of separation science. Interest in these materials has been fueled by observations that solute-sorbent interactions are mainly adsorptive in nature and thus selectivities are frequently quite different from what is observed with small organic ligands bonded to porous substrates. However, despite over four decades of intense study and development of these materials for use in reversed phase liquid chromatography, wide adoption continues to be hindered by a few significant, negative attributes of these materials, most notably irreversible adsorption and poor peak shape and separation efficiency for some classes of compounds. In this work we describe the results of a study aimed at characterization of C60 fullerene-modified silica (FMS) materials that we believe nicely complement existing graphite-like carbonaceous phases for use in liquid chromatography. Since their first synthesis about 20 years ago, FMS materials have received surprisingly little attention, which has been focused mainly on the separation of highly aromatic compounds. Here, we use retention data for well established sets of both nonionizable and ionizable low molecular weight probe solutes to demonstrate that FMS both exhibits graphite-like characteristics (i.e., selectivity for structural isomers and enhanced retention of polar compounds) and has selectivity characteristics that are largely unique in comparison to over 600 other materials used for reversed-phase liquid chromatography. In addition, FMS exhibits much improved peak shape and separation efficiency for compounds that are known to be problematic when separated by use of graphite-like phases. This combination of attributes makes FMS an excellent complement to graphite-like phases for use in two-dimensional liquid chromatography, where unique selectivity compared to conventional bonded reversed phase materials, along with good peak shape and separation efficiency are of paramount importance for successful two-dimensional liquid chromatographic separations. PMID- 24215428 TI - Structural and biochemical characterization of the bilin lyase CpcS from Thermosynechococcus elongatus. AB - Cyanobacterial phycobiliproteins have evolved to capture light energy over most of the visible spectrum due to their bilin chromophores, which are linear tetrapyrroles that have been covalently attached by enzymes called bilin lyases. We report here the crystal structure of a bilin lyase of the CpcS family from Thermosynechococcus elongatus (TeCpcS-III). TeCpcS-III is a 10-stranded beta barrel with two alpha helices and belongs to the lipocalin structural family. TeCpcS-III catalyzes both cognate as well as noncognate bilin attachment to a variety of phycobiliprotein subunits. TeCpcS-III ligates phycocyanobilin, phycoerythrobilin, and phytochromobilin to the alpha and beta subunits of allophycocyanin and to the beta subunit of phycocyanin at the Cys82-equivalent position in all cases. The active form of TeCpcS-III is a dimer, which is consistent with the structure observed in the crystal. With the use of the UnaG protein and its association with bilirubin as a guide, a model for the association between the native substrate, phycocyanobilin, and TeCpcS was produced. PMID- 24215431 TI - Hemisynthesis and structural and chromatic characterization of delphinidin 3-O glucoside-vescalagin hybrid pigments. AB - During red wine maturation in the presence of oak wood, reactions involving anthocyanins and ellagitannins might affect wine organoleptic properties such as color and astringency. In this work, the condensation reaction between myrtillin (delphinidin 3-O-glucoside) and vescalagin has been performed to determine the behavior of this anthocyanin in this kind of reaction and to assess the possible impact of such a reaction in wine color modulation. Two different hybrid pigments have been hemisynthetized and characterized by HPLC-DAD-MS and NMR spectroscopy. These pigments have been identified as 1-deoxyvescalagin-(1beta->8)-myrtillin (major) and 1-deoxyvescalagin-(1beta->6)-myrtillin (minor). The minor pigment could be formed both by the condensation reaction and by a regioisomerization process from the major pigment. Moreover, the chromatic properties of these pigments have been studied and compared to those of myrtillin. The hybrid pigments showed an important bathochromic shift (ca. 20 nm) in the maximum absorbance wavelength and lower molar absorption coefficients. PMID- 24215432 TI - Interaction of cationic protoberberine alkaloids with human serum albumin. No spectroscopic evidence on binding to Sudlow's site 1. AB - Physicochemical studies on drug interactions with human serum albumin (HSA) are relevant for elucidation, at the molecular level, of the processes occurring in vivo. In this work using optical spectroscopic methods (fluorescence, absorption, circular dichroism), we have investigated aqueous HSA solutions containing pharmaceutically important isoquinoline alkaloids, berberine and palmatine. The primary objective was to verify whether the two compounds are located in the subdomain IIA of the secondary HSA structure as reported in literature. We prove that the excited state of Trp214 residue is not quenched by the alkaloids; all observed changes in fluorescence spectra are due to inner filter effects. Furthermore, differential absorption spectra indicate that the ligands remain in a waterlike microenvironment. We infer that bound alkaloid molecules are located at the protein/water interface. Yet, such binding mode can induce some unfolding of the HSA molecule detectable in the far-UV circular dichroism (CD) spectra. We have also performed, for the first time, pulse radiolysis studies of hydrated electron scavenging in the HSA/alkaloid systems and have measured steady-state absorption spectra of irradiated samples. The results reveal that neither berberine nor palmatine is effectively protected by the protein against one electron reduction, which is consistent with the aforementioned conclusion. PMID- 24215433 TI - Language helps children succeed on a classic analogy task. AB - Adult humans show exceptional relational ability relative to other species. In this research, we trace the development of this ability in young children. We used a task widely used in comparative research-the relational match-to-sample task, which requires participants to notice and match the identity relation: for example, AA should match BB instead of CD. Despite the simplicity of this relation, children under 4 years of age failed to pass this test (Experiment 1), and their performance did not improve even with initial feedback (Experiment 2). In Experiments 3 and 4, we found that two kinds of symbolic-linguistic experience can facilitate relational reasoning in young children. Our findings suggest that children learn to become adept analogical thinkers, and that language fosters this learning in at least two distinct ways. PMID- 24215434 TI - Life-time prevalence and psychosocial correlates of adolescent direct self injurious behavior: a comparative study of findings in 11 European countries. AB - OBJECTIVES: To investigate the prevalence and associated psychosocial factors of occasional and repetitive direct self-injurious behavior (D-SIB), such as self cutting, -burning, -biting, -hitting, and skin damage by other methods, in representative adolescent samples from 11 European countries. METHODS: Cross sectional assessment of adolescents was performed within the European Union funded project, Saving and Empowering Young Lives in Europe (SEYLE), which was conducted in 11 European countries. The representative sample comprised 12,068 adolescents (F/M: 6,717/5,351; mean age: 14.9 +/- 0.89) recruited from randomly selected schools. Frequency of D-SIB was assessed by a modified 6-item questionnaire based on previously used versions of the Deliberate Self-Harm Inventory (DSHI). In addition, a broad range of demographic, social, and psychological factors was assessed. RESULTS: Overall lifetime prevalence of D-SIB was 27.6%; 19.7% reported occasional D-SIB and 7.8% repetitive D-SIB. Lifetime prevalence ranged from 17.1% to 38.6% across countries. Estonia, France, Germany, and Israel had the highest lifetime rates of D-SIB, while students from Hungary, Ireland, and Italy reported low rates. Suicidality as well as anxiety and depressive symptoms had the highest odds ratios for both occasional and repetitive D-SIB. There was a strong association of D-SIB with both psychopathology and risk-behaviors, including family related neglect and peer related rejection/victimization. Associations between psychosocial variables and D-SIB were strongly influenced by both gender and country. Only a minor proportion of the adolescents who reported D-SIB ever received medical treatment. CONCLUSION: These results suggest high lifetime prevalence of D-SIB in European adolescents. Prevalence as well as psychosocial correlates seems to be significantly influenced by both gender and country. These results support the need for a multidimensional approach to better understand the development of SIB and facilitate culturally adapted prevention/intervention. PMID- 24215435 TI - Comments on "Prevented mortality and greenhouse gas emissions from historical and projected nuclear power". PMID- 24215437 TI - Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury. AB - Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb) dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O2.-) and hydrogen peroxide (H2O2) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H2O2-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease. PMID- 24215438 TI - Immunisation coverage and its associations in rural Tanzanian infants. AB - INTRODUCTION: In Tanzania, vaccination rates (VRs) range from 80% to 90% for standard vaccines, but little information is available about rural populations and nomadic pastoralists. This study investigates levels and trends of the immunisation status of infants at eight mobile reproductive-and-child-health (RCH) clinics in a rural area in northern Tanzania (with a large multi-tribal population that has a significant population of nomadic pastoralists) for the years 1998, 1999, 2006 and 2007. In addition, the influence of tribal affiliation and health system-related factors on the immunisation status in this population is analysed. METHODS: Vaccination data of 3868 infants for the standard bacillus Calmette-Guerin (BCG), poliomyelitis, diphtheria, pertussis, tetanus and measles vaccines were obtained from the RCH clinic records retrospectively, and coverage for both single vaccines and full vaccination by the end of first year of life were calculated. These results were correlated with data on predominant tribal affiliation at the clinic site, skilled attendance at birth, service provision and vaccine availability as independent variables. RESULTS: In 1998, the full vaccination rate (FVR) across all RCH clinics was 72%, significantly higher than in the other years (1999: 58%; 2006: 58%; 2007: 57%) (p<0.0001). BCG and measles VRs were highest in 1998 and 1999, whereas VR was lowest for poliomyelitis in 1999, and for diphtheria-pertussis-tetanus in 2007 (all p<0.001). Measles VR showed a declining trend (1998: 72%; 1999: 73%; 2006: 62%; 2007: 59%) affecting the FVR, except in 1999 when poliomyelitis VR was lower (67%). FVR > 80% was only achieved at one clinic during 3 years. No clinic showed a consistent increase of VRs over time. In univariate analysis, predominant tribal affiliation (Datoga tribe) was associated with a low FVR (odds ratio (OR) 4.6 (95% confidence interval (CI) 3.8-5.5)), as were low rates of skilled attendance at birth (OR 3.6 (CI 2.9-4.4)). Other health system-related factors associated with low FVRs included interruption of scheduled monthly immunisation clinics (OR 9.8 (CI 2.1 45.5)) and lack of vaccines (OR 1.2-2.9, depending on vaccine). In multivariate analysis, predominant Datoga tribal affiliation and lack of vaccines retained their association with the risk of low rates of vaccination. CONCLUSIONS: Vaccination rates in this difficult-to-reach population are markedly lower than the national average for almost all years and clinics. Affiliation to the nomadic Datoga tribe and lack of vaccines determine VRs in this rural population. Improvements in immunisation service delivery, vaccine availability, stronger involvement of the nomadic communities and special outreach services for this population are required to improve VRs in these remote areas of Tanzania. PMID- 24215436 TI - In vivo confocal microscopy of the ocular surface: from bench to bedside. AB - In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move "from bench to bedside". IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease- or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis. PMID- 24215439 TI - Nanosoldering carbon nanotube junctions by local chemical vapor deposition for improved device performance. AB - The performance of carbon nanotube network (CNN) devices is usually limited by the high resistance of individual nanotube junctions (NJs). We present a novel method to reduce this resistance through a nanoscale chemical vapor deposition (CVD) process. By passing current through the devices in the presence of a gaseous CVD precursor, localized nanoscale Joule heating induced at the NJs stimulates the selective and self-limiting deposition of metallic nanosolder. The effectiveness of this nanosoldering process depends on the work function of the deposited metal (here Pd or HfB2), and it can improve the on/off current ratio of a CNN device by nearly an order of magnitude. This nanosoldering technique could also be applied to other device types where nanoscale resistance components limit overall device performance. PMID- 24215441 TI - Emerging roles of orphan nuclear receptors in cancer. AB - A growing body of evidence suggests that a subset of orphan nuclear receptors are amplified and prognostic for some human cancers. However, the specific roles of these orphan nuclear receptors in tumor progression and their utility as drug targets are not fully understood. In this review, we summarize recent progress in elucidating the direct and indirect involvement of orphan nuclear receptors in cancer as well as their therapeutic potential in a variety of human cancers. Furthermore, we contrast the role of orphan nuclear receptors in cancer with the known roles of estrogen receptor and androgen receptor in hormone-dependent cancers. PMID- 24215440 TI - Trafficking of epidermal growth factor receptor ligands in polarized epithelial cells. AB - A largely unilamellar epithelial layer lines body cavities and organ ducts such as the digestive tract and kidney tubules. This polarized epithelium is composed of biochemically and functionally separate apical and basolateral surfaces. The epidermal growth factor receptor (EGFR) signaling pathway is a critical regulator of epithelial homeostasis and is perturbed in a number of epithelial disorders. It is underappreciated that in vivo EGFR signaling is most often initiated by cell-surface delivery and processing of one of seven transmembrane ligands, resulting in release of the soluble form that binds EGFR. In polarized epithelial cells, EGFR is restricted largely to the basolateral surface, and apical or basolateral ligand delivery therefore has important biological consequences. In vitro approaches have been used to study the biosynthesis, cell-surface delivery, proteolytic processing, and release of soluble EGFR ligands in polarized epithelial cells. We review these results, discuss their relevance to normal physiology, and demonstrate the pathophysiological consequences of aberrant trafficking. These studies have uncovered a rich diversity of apico-basolateral trafficking mechanisms among the EGFR ligands, provided insights into the pathogenesis of an inherited magnesium-wasting disorder of the kidney (isolated renal hypomagnesemia), and identified a new mode of EGFR ligand signaling via exosomes. PMID- 24215444 TI - Repeat antenatal HIV testing in the third trimester: a study of feasibility and maternal uptake rates. AB - OBJECTIVES: The study aimed to assess the feasibility and acceptability of third trimester antenatal HIV testing within our service after two cases of HIV seroconversion in pregnancy were noted in 2008. North American Guidelines recommend universal third-trimester HIV testing in areas with an HIV prevalence of more than 1 per 1000. The HIV prevalence rate in our area is 3.01 per 1000. METHODS: Pregnant women prior to 28 weeks of gestation were recruited at booking between 1 September 2008 and 31 August 2009 and offered an additional third trimester HIV test. Consent was obtained and testing was performed by hospital and community midwives. Information was entered into a modified existing electronic maternity database. A qualitative e-mail survey of midwives investigated barriers to participation in the study. RESULTS: A total of 4134 women delivered; three (< 0.1%) declined first-trimester testing. Twenty-two women (0.5%) tested HIV positive, of whom six were newly diagnosed. Overall, 2934 of 4134 women (71%) were offered and accepted a third-trimester HIV test and had results available. Data were unavailable for 195 women (4.7%). A total of 663 of 4131 women (16%) were not offered a third-trimester test. Of 3273 women documented as having been offered a test, 3177 (97.1%) accepted. There were no positive third-trimester tests. Forty of 50 (80%) midwives surveyed responded with questionnaire feedback and cited lack of national policy and extra workload as barriers to performing third-trimester testing. CONCLUSIONS: Third-trimester testing was feasible and consent rates were high in those offered repeat testing. Third-trimester testing has the potential to prevent paediatric HIV infection and universal testing should be considered in high-prevalence areas. PMID- 24215445 TI - Obesity and high waist circumference are associated with low circulating pentraxin-3 in acute coronary syndrome. AB - BACKGROUND: Long pentraxin 3 (PTX3) is a component of the pentraxin superfamily and a potential marker of vascular damage and inflammation, associated with negative outcome in patients with acute coronary syndromes (ACS). Obesity is a risk factor for cardiovascular disease and PTX3 production is reported in abdominal adipose tissue. Low PTX3 is however reported in the obese population, and obesity per se may be associated with less negative ACS outcome. METHODS: We investigated the potential impact of obesity and high waist circumference (reflecting abdominal fat accumulation) on plasma PTX3 concentration in ACS patients (n = 72, 20 obese) compared to age-, sex- and BMI-matched non-ACS individuals. RESULTS: Both obese and non-obese ACS patients had higher PTX3 than matched non-ACS counterparts, but PTX3 was lower in obese than non-obese individuals in both groups (all P < 0.05). PTX3 was also lower in ACS subjects with high than in those with normal waist circumference (WC). Plasma PTX3 was accordingly associated negatively with BMI and WC, independently of age and plasma creatinine. No associations were observed between PTX3 and plasma insulin, glucose or the short pentraxin and validated inflammation marker C-reactive protein, that was higher in ACS than in non-ACS individuals independently of BMI or WC. CONCLUSIONS: Obesity is associated with low circulating PTX3 in ACS. This association is also observed in the presence of abdominal fat accumulation as reflected by elevated waist circumference. Low PTX3 is a novel potential modulator of tissue damage and outcome in obese ACS patients. PMID- 24215443 TI - Plasticity of dendritic spines: subcompartmentalization of signaling. AB - The ability to induce and study neuronal plasticity in single dendritic spines has greatly advanced our understanding of the signaling mechanisms that mediate long-term potentiation. It is now clear that in addition to compartmentalization by the individual spine, subcompartmentalization of biochemical signals occurs at specialized microdomains within the spine. The spatiotemporal coordination of these complex cascades allows for the concomitant remodeling of the postsynaptic density and actin spinoskeleton and for the regulation of membrane traffic to express functional and structural plasticity. Here, we highlight recent findings in the signaling cascades at spine microdomains as well as the challenges and approaches to studying plasticity at the spine level. PMID- 24215442 TI - Nanoparticles, lung injury, and the role of oxidant stress. AB - The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion. PMID- 24215446 TI - Understanding childbirth practices as an organizational cultural phenomenon: a conceptual framework. AB - Understanding the main values and beliefs that might promote humanized birth practices in the specialized hospitals requires articulating the theoretical knowledge of the social and cultural characteristics of the childbirth field and the relations between these and the institution. This paper aims to provide a conceptual framework allowing examination of childbirth practices through the lens of an organizational culture theory. A literature review performed to extrapolate the social and cultural factors contribute to birth practices and the factors likely overlap and mutually reinforce one another, instead of complying with the organizational culture of the birth place. The proposed conceptual framework in this paper examined childbirth patterns as an organizational cultural phenomenon in a highly specialized hospital, in Montreal, Canada. Allaire and Firsirotu's organizational culture theory served as a guide in the development of the framework. We discussed the application of our conceptual model in understanding the influences of organizational culture components in the humanization of birth practices in the highly specialized hospitals and explained how these components configure both the birth practice and women's choice in highly specialized hospitals. The proposed framework can be used as a tool for understanding the barriers and facilitating factors encountered birth practices in specialized hospitals. PMID- 24215448 TI - Atrial electromechanical conduction delay in patients with neurocardiogenic syncope. AB - AIM: We aimed to investigate the presence of atrial electromechanical conduction delay in patients with neurocardiogenic syncope, which was diagnosed with head-up tilt table test (HUTT). MATERIALS AND METHODS: A total of 29 patients (mean age: 30.6 +/- 15.9 years) with vasovagal syncope, as diagnosed by HUTT, and 23 healthy control subjects (mean age: 34.7 +/- 16.3 years) with a negative HUTT were enrolled to the study. Atrial electromechanical conduction delay was defined as the time elapsed from the beginning of the P wave in the electrogardiogram to the beginning of the Am wave in tissue Doppler. RESULTS: There was no statistically significant difference between the groups in terms of interatrial conduction delay, whereas the difference was significant with regard to the right intraatrial electromechanical conduction delay (P < 0.01) and the left intraatrial electromechanical conduction delay (P < 0.0001). There was a negative correlation between the left intraatrial electromechanical conduction delay and the right intraatrial electromechanical conduction delay (r = -0.486, P = 0.001), whereas a positive correlation was present with the interatrial electromechanical conduction delay (r = 0.507, P = 0.001). CONCLUSION: In this study, the tissue Doppler method revealed that there is left and right intraatrial electromechanical conduction delay in patients with vasovagal syncope. The impact and role of atrial conduction delay as a pathophysiological determinant should be confirmed in further studies. PMID- 24215450 TI - Physicochemical properties of the novel biphasic hydroxyapatite-magnesium phosphate biomaterial. AB - Besides high-temperature calcium phosphates (CaPs), low-temperature calcium phosphate bone cements (CPCs), due to excellent biological properties: bioactivity, biocompability and osteoconductivity, are successfully used as bone substitutes. However, some disadvantages, related mainly to their low resorption rate and poor mechanical properties result in limited range of applications of these implant materials to non-loaded places in the skeletal system. To overcome this problem, magnesium phosphate cements (MPCs) with high strength have been considered as biomaterials. The main disadvantage of MPCs is that the acid-base setting reaction is an exothermic process that must be strictly controlled to avoid tissue necrosis. In this work, a new composite bone substitute (Hydroxyapatite Magnesium Phosphate Material - HMPM) based on hydroxyapatite (HA) and magnesium phosphate cement (MPC) with sodium pyrophosphate applied as a retardant of setting reaction was obtained. Its setting time was adequate for clinical applications. Combining properties of HA and MPC has made it possible to obtain microporous (showing bimodal pore size distribution in the range of 0.005 1.700 micrometers) potential implant material showing good surgical handiness and sufficient mechanical strength. Effectiveness of sodium pyrophosphate as a retardant of exothermic setting reaction of the new cement formulation was confirmed. After setting and hardening, the material consisted of hydroxyapatite and struvite as crystalline phases. Unreacted magnesium oxide was not detected. PMID- 24215451 TI - Neuroimaging training among neuropsychologists: a survey of the state of current training and recommendations for trainees. AB - Neuroimaging has gained widespread use in neuropsychological research and practice. However, there are neither established guidelines on how neuropsychologists might become competent researchers or consumers of neuroimaging data, nor any published studies describing the state of neuroimaging training among neuropsychologists. We report the results of two online surveys, one of 13 expert neuropsychologist-neuroimagers whose responses informed the formulation of a second, larger survey to neuropsychologists-at-large that were a random selection of a third of the members of the International Neuropsychological Society and American Academy of Clinical Neuropsychology. A total of 237 doctoral-level neuropsychologists, or 15.3% of potential participants, provided complete responses. Most respondents (69.2%) received training in neuroimaging, mostly at the post-doctoral level, largely through independent study, clinical conferences, instruction by clinical supervisors, and individualized mentoring, on topics such as neuroimaging modalities in neurology, neuroanatomy, and the appropriate information to glean from neuroradiology reports. Of the remaining respondents who did not receive training in neuroimaging, 64.4% indicated that such training would be very or extremely beneficial to one's career as a neuropsychologist. Both neuropsychologist neuroimagers and neuropsychologists-at-large provided specific recommendations for training. Findings from this initial effort will guide trainees who seek to develop competence in neuroimaging, and inform future formulations of neuropsychological training. PMID- 24215447 TI - Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art. AB - INTRODUCTION: Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also the ability to minimize the potentially hazardous off-target effects. AREAS COVERED: This review covers the role of intranasal insulin therapy for cognitive impairment and neurodegeneration, particularly AD. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The review provides evidence that brain insulin resistance is an important and early abnormality in AD, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. EXPERT OPINION: Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy and specificity of intranasal insulin therapy. PMID- 24215452 TI - Dapsone-induced methemoglobinemia in renal transplant recipients: more prevalent than previously thought. AB - BACKGROUND: After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients. METHODS: Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors. RESULTS: Twelve (46%) patients developed MHb (levels 6.4 +/- 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 +/- 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002). CONCLUSION: This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients. PMID- 24215453 TI - Suppression of quenching in plasmon-enhanced luminescence via rapid intraparticle energy transfer in doped quantum dots. AB - We show the suppression of luminescence quenching by metal nanoparticles (MNPs) in the plasmon enhancement of luminescence via fast sensitized energy transfer in Mn-doped quantum dots (QDs). The rapid intraparticle energy transfer between exciton and Mn, occurring on a few picoseconds time scale, separates the absorber (exciton) from the emitter (Mn), whose emission is detuned far from the plasmon of the MNP. The rapid temporal separation of the absorber and emitter combined with the reduced spectral overlap between Mn and plasmonic MNP suppresses the quenching of the luminescence while taking advantage of the plasmon-enhanced excitation. We compared the plasmon enhancement of exciton and Mn luminescence intensities in undoped and doped QDs simultaneously as a function of the distance between MNP and QD layers in a multilayer structure to examine the expected advantage of the reduced quenching in the sensitized luminescence. At the optimum MNP-QD layer distance, Mn luminescence exhibits stronger net enhancement than that of the exciton, which can be explained with a model incorporating fast sensitization along with reduced emitter-MNP spectral overlap. This study demonstrates that materials exhibiting fast sensitized luminescence that is sufficiently red-shifted from that of the sensitizer can be superior to usual luminophores in harvesting plasmon enhancement of luminescence by suppressing quenching. PMID- 24215454 TI - Morphological control of multihollow polymer latex particles through a controlled phase separation in the seeded emulsion polymerization. AB - In this work, we first reported that the phase separation can take place both inside and outside of a multihollow-structured cross-linked seed microspheres swollen by styrene monomers in water during the radiation-induced seeded emulsion polymerization. The phase separation process in these two opposite directions will determine the morphology of final latex particles. First, sulfonated cross linked polystyrene (SCPS) seed microspheres were swollen by styrene in water. Water will permeate into the SCPS seed microspheres during the swelling process, forced by the osmotic pressure produced by the strong hydrophilicity of the sulfonic acid groups. New aqueous phases are created and stabilized by the hydrophilic -SO3H groups, resulting in a multihollow structure of swollen SCPS seed microspheres. When the polymerization of styrene is induced by (60)Co gamma ray radiation, the phase separation of newly formed polystyrene phase will occur at the seed microsphere-water interface inside and/or outside of the SCPS seed microspheres through adjusting the diameter of seed microsphere, the content of cross-link agent, and the sulfonation degree of SCPS seed microspheres. As a result, SCPS latex particles with a variety of special morphologies, such as spherical multihollow, plum-like, and walnut-like latex particles were obtained. The results of this study provide not only a simple and interesting way to design and synthesize multihollow polymer latex particles with controllable surface morphologies but also a better understanding on phase separation mechanism during the swelling and polymerization of monomers in cross-linked amphiphilic polymer networks. PMID- 24215456 TI - Isothermally sensitive detection of serum circulating miRNAs for lung cancer diagnosis. AB - Tumor-derived miRNAs in serum are emerging as the new noninvasive biomarkers for the diagnosis of human cancers, especially at their early stage. An ideal method with high sensitivity, excellent selectivity, a simple procedure, and small amounts of starting materials is imperative for the detection of clinic circulating miRNAs. Here, we develop a new method for isothermally sensitive detection of serum miRNAs using hairpin probe-based rolling circle amplification (HP-RCA). This method exhibits ultrahigh sensitivity toward lung cancer-related miR-486-5p with a detection limit of as low as 10 fM and a large dynamic range of 6 orders of magnitude, and it can even discriminate miR-486-5p from both miRNAs with high sequence homology and its precursors (pre-miRNAs). More importantly, this method can directly and accurately distinguish the expression of serum miR 486-5p among six nonsmall-cell lung carcinoma (NSCLC) patients and six healthy persons, holding a great potential for further applications in the clinical diagnosis of lung cancers. PMID- 24215455 TI - The cellular environment stabilizes adenine riboswitch RNA structure. AB - There are large differences between the intracellular environment and the conditions widely used to study RNA structure and function in vitro. To assess the effects of the crowded cellular environment on RNA, we examined the structure and ligand binding function of the adenine riboswitch aptamer domain in healthy, growing Escherichia coli cells at single-nucleotide resolution on the minute time scale using SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension). The ligand-bound aptamer structure is essentially the same in cells and in buffer at 1 mM Mg(2+), the approximate Mg(2+) concentration we measured in cells. In contrast, the in-cell conformation of the ligand-free aptamer is much more similar to the fully folded ligand-bound state. Even adding high Mg(2+) concentrations to the buffer used for in vitro analyses did not yield the conformation observed for the free aptamer in cells. The cellular environment thus stabilizes the aptamer significantly more than does Mg(2+) alone. Our results show that the intracellular environment has a large effect on RNA structure that ultimately favors highly organized conformations. PMID- 24215457 TI - Development of a Nasonia vitripennis outbred laboratory population for genetic analysis. AB - The parasitoid wasp genus Nasonia has rapidly become a genetic model system for developmental and evolutionary biology. The release of its genome sequence led to the development of high-resolution genomic tools, for both interspecific and intraspecific research, which has resulted in great advances in understanding Nasonia biology. To further advance the utility of Nasonia vitripennis as a genetic model system and to be able to fully exploit the advantages of its fully sequenced and annotated genome, we developed a genetically variable and well characterized experimental population. In this study, we describe the establishment of the genetically diverse HVRx laboratory population from strains collected from the field in the Netherlands. We established a maintenance method that retains genetic variation over generations of culturing in the laboratory. As a characterization of its genetic composition, we provide data on the standing genetic variation and estimate the effective population size (N(e)) by microsatellite analysis. A genome-wide description of polymorphism is provided through pooled resequencing, which yielded 417,331 high-quality SNPs spanning all five Nasonia chromosomes. The HVRx population and its characterization are freely available as a community resource for investigators seeking to elucidate the genetic basis of complex trait variation using the Nasonia model system. PMID- 24215458 TI - Ratio of "A-type" to "B-type" proanthocyanidin interflavan bonds affects extra intestinal pathogenic Escherichia coli invasion of gut epithelial cells. AB - Gut colonization by extra-intestinal pathogenic Escherichia coli (ExPEC) increases the risk of subsequent infections, including urinary tract infection and septicemia. Previous work suggests that cranberry proanthocyanidins (PAC) interact with bacterial surface factors, altering bacterial interaction with host cells. Methods were developed to determine if ratios of "A-type" to "B-type" interflavan bonds in PAC affect ExPEC agglutination and invasion of enterocytes. In cranberries, 94.5% of PAC contain one or more "A-type" bonds, whereas in apples, 88.3% of PAC contain exclusively "B-type" bonds. Results show that cranberry "A-type" PAC have greater bioactivity than apple "B-type" PAC for increasing ExPEC agglutination and decreasing ExPEC epithelial cell invasion. PMID- 24215459 TI - Effect of aging the glass of isotactic polybutene-1 on form II nucleation and cold crystallization. AB - The effect of aging initially fully amorphous isotactic polybutene-1 (iPB-1) at temperatures between 243 and 283 K on form II nucleation and cold crystallization has been quantified by fast scanning chip calorimetry. Aging of amorphous iPB-1 at temperatures close to the glass transition temperature leads to formation of nuclei which accelerate subsequent cold crystallization. Analysis of the enthalpy of cold crystallization on heating differently aged samples revealed a maximum rate of nucleation at around 265 K. In contrast, the maximum rate of form II crystallization is observed at distinctly higher temperature of 330-340 K. It is suggested that formation of form II crystal nuclei in the glassy state requires prior densification of the glass since acceleration of cold crystallization on heating the aged glass is detected only after completion of the enthalpy relaxation. The analysis of the rates of nucleation and cold crystallization of iPB-1 at low temperatures is a necessary completion of prior work on the phase transition behavior, and contributes to further understanding of mechanisms of crystal nucleation in polymers. PMID- 24215460 TI - Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and disrupts endoplasmic reticulum-associated protein degradation. AB - Protein aggregation is a common feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. How protein aggregates are formed and contribute to neurodegeneration, however, is not clear. Mutation of Ubiquilin 2 (UBQLN2) has recently been linked to ALS and frontotemporal lobar degeneration. Therefore, we examined the effect of ALS-linked UBQLN2 mutation on endoplasmic reticulum associated protein degradation (ERAD). Compared to its wild-type counterpart, mutated UBQLN2 caused greater accumulation of the ERAD substrate Hong Kong variant of alpha-1-antitrypsin, although ERAD was disturbed by both UBQLN2 over expression and knockdown. Also, UBQLN2 interacted with ubiquitin regulatory X domain-containing protein 8 (UBXD8) in vitro and in vivo, and this interaction was impaired by pathogenic mutation of UBQLN2. As UBXD8 is an endoplasmic membrane protein involved in the translocation of ubiquitinated ERAD substrates, UBQLN2 likely cooperates with UBXD8 to transport defective proteins from the endoplasmic reticulum to the cytosol for degradation, and this cell-protective function is disturbed by pathogenic mutation of UBQLN2. PMID- 24215461 TI - In vitro susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytes. AB - To investigate the antifungal drug susceptibility of fungi responsible for dermatomycoses, minimum inhibition concentration (MIC) tests were performed in 44 strains of dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum and Epidermophyton floccosum, with six antifungal drugs (amorolfine, terbinafine, butenafine, ketoconazole, itraconazole and bifonazole) by broth microdilution assay according to Clinical Laboratory Standard Institute protocols. Six possible dermatomycosis-causing non dermatophytic fungi were also tested. The two major causes of tinea, T. rubrum and T. mentagrophytes, showed significantly different sensitivities to ketoconazole and bifonazole. Clinically derived dermatophytes were sensitive to the six antifungal drugs tested. However, non-dermatophytes, especially Fusarium spp., tended to be resistant to these antifungal drugs. In Trichophyton spp., the MICs of non-azole drugs had narrower distributions than those of azoles. To evaluate the effects of antifungal drug combinations, the fractional inhibitory concentration index was calculated for the combination of amorolfine and itraconazole as representative external and internal drugs for dermatophytes. It was found that this combination had synergistic or additive effects on most dermatophytes, and had no antagonistic effects. The variation in susceptibility of clinically derived fungal isolates indicates that identification of causative fungi is indispensable for appropriately choosing effective antifungal drugs in the early stages of infection. The results of combination assay suggest that multiple drugs with different antifungal mechanisms against growth of dermatophytes should be used to treat refractory dermatomycoses, especially onychomycosis. PMID- 24215462 TI - Mechanotransduction channels of the trabecular meshwork. AB - PURPOSE: To determine whether the trabecular meshwork (TM), like the other organs engaged in filter like activities (such as kidneys), show the expression of known mechanotransduction channels at protein level. METHODS: Human donor eye globes (n = 20), Donor eye derived TM tissue and primary TM cells were utilized for these studies. Commercially available antibodies to channels, immunohisto- and immunocytochemistry, Western blot and mass spectrometric analyses were performed to determine the presence of mechanosensitive channels at protein level. The study was performed adhering to tenets of declaration of Helsinki. RESULTS: We demonstrate here the presence of 11 mechanotransduction channels (Piezo1, Piezo2, TASK1, TREK1, TRPA1, TRPC1, TRPC2, TRPC3, TRPC6, TRPM2, TRPP2) as expressed protein in the TM tissue and at the isolated TM cell level. Presence of at least one known isoform of these channels was demonstrated using Western blot analyses. CONCLUSIONS: We demonstrated the presence of 11 mechanotransduction channels in the TM and in isolated TM cells at protein level. Demonstration of these channels as proteins at tissue and cellular level will pave the way for further experimentation. PMID- 24215463 TI - Secondary metabolites from marine-derived microorganisms. AB - In the search for novel and bioactive molecules for drug discovery, marine derived natural resources, especially marine microorganisms are becoming an important and interesting research area. This study covers the literature published after 2008 on secondary metabolites of marine-derived microorganisms. The emphasis was on new compounds with the relevant biological activities, strain information, and country of origin. New compounds without biological activity were not included. PMID- 24215464 TI - Potential involvement of intracellular pH in a mouse model of amyotrophic lateral sclerosis. PMID- 24215465 TI - Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to child transmission of HIV: a prospective cohort study. AB - OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association. PMID- 24215466 TI - The electronic structure of CdSe/CdS core/shell seeded nanorods: type-I or quasi type-II? AB - The electronic structure of CdSe/CdS core/shell seeded nanorods of experimentally relevant size is studied using a combination of molecular dynamics and semiempirical pseudopotential techniques with the aim to address the transition from type-I to a quasi-type-II band alignment. The hole is found to be localized in the core region regardless of its size. The overlap of the electron density with the core region depends markedly on the size of the CdSe core. For small cores, we observe little overlap, consistent with type-II behavior. For large cores, significant core-overlap of a number of excitonic states can lead to type I behavior. When electron-hole interactions are taken into account, the core overlap is further increased. Our calculations indicate that the observed transition from type-II to type-I is largely due to simple volume effects and not to band alignment. PMID- 24215467 TI - Enhanced activation of the left hemisphere promotes normative decision making. AB - Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories. PMID- 24215468 TI - Attempt to improve the performance of pyrrole-containing dyes in dye sensitized solar cells by adjusting isolation groups. AB - Four new pyrrole-based organic sensitizers with different isolation groups were conveniently synthesized and applied to dye sensitized solar cells (DSCs). The introduction of isolation group in the side chain could both suppress the formation of dye aggregates and electron recombination. Especially, when two pieces of D-pi-A chromophore moieties shared one isolation group to construct the "H" type dye, the performance was further improved. Consequently, in the corresponding solar cell of LI-57, a short-circuit photocurrent density (Jsc) was tested to be 13.85 mA cm(-2), while 0.72 V for the open-circuit photovoltage (Voc), 0.64 for the fill factor (FF), and 6.43% for the overall conversion efficiency (eta), exceeding its analogue LI-55 (5.94%) with the same isolation group. The results demonstrated that both the size (bulk and shape) and the linkage mode between the D-pi-A chromophores and the isolation groups, could affect the performance of sensitizers in DSCs in a large degree, providing a new approach to optimize the chemical structure of dyes to achieve high conversion efficiencies. PMID- 24215469 TI - Plasma copeptin levels are inversely associated with intima-media-thickness in men: the population-based KORA F4 study. AB - BACKGROUND: Elevated plasma preprovasopressin (copeptin) levels are associated with cardiovascular complications as well as with an increased risk for type 2 diabetes (T2D). Here, we studied, whether plasma copeptin is related to carotid intima-media thickness (IMT), a measure of early atherosclerosis, and may thus be one explanation for the high cardiovascular risk in T2D. METHODS: Plasma concentrations of copeptin and IMT of the common carotid artery were determined in 1275 participants of the population-based KORA F4 study. We used linear regression models to investigate associations between copeptin levels and IMT. RESULTS: In the whole study group, copeptin levels were not significantly associated with IMT after adjustment for age and sex. Copeptin and IMT were significantly inversely associated after multivariable adjustment in the total cohort (beta = -0.020 mm, 95% CI: -0.037 mm; -0.003 mm), in men (beta = -0.035 mm, 95% CI: -0.061 mm; -0.009 mm) and in study participants with prediabetes (beta = -0.041 mm, 95% CI: -0.078 mm; -0.005 mm) comparing quartile 4 vs quartile 1. The negative association of copeptin and IMT in men was present after adjustment for age alone. In women and patients with T2D, copeptin was not significantly associated with IMT. CONCLUSIONS: Plasma copeptin was not associated with an increased IMT in our study cohort. In contrast, copeptin levels were related to a lower IMT in men and subjects with prediabetes, suggesting that elevated copeptin concentrations do not exert proatherogenic effects on carotid arteries. PMID- 24215471 TI - ZnO nanofertilizer and He Ne laser irradiation for promoting growth and yield of sweet basil plant. AB - This study was conducted to evaluate the effectiveness of zinc nanofertilizer strategy on sweet basil yield, through alone application or combined with pre sowing laser irradiation. Furthermore, evaluate the growth of plant and the level of active essential oil constituents. Zinc oxide (ZnO) nanoparticles (NPs) were synthesized, and transmission electron microscope revealed particle size of approximately 10.5-15.5 nm. ZnO NPs were applied to sweet basil plants by foliar spray at varying concentrations (10, 20 and 30 mg/L); He Ne laser of power 3mW was used for red light irradiation of sweet basil seeds for 2 min. exposure time. Total chlorophyll, total carbohydrate, essential oil levels, zinc content, plant height, branches/plant and fresh weight were measured. In general, the combined foliar spray application of ZnO nanofertilizer with pre-sowing He Ne laser irradiation showed more effectiveness than ZnO nanofertilizer alone and 20mg/L concentration gave the highest results of all measured traits. Statistical analysis (t-test) showed significant differences among the effects of the various concentrations of zinc oxide NPs on these attributes. The results showed an inverse relationship between the total carbohydrate content and the percentage of essential oil in the leaves. Together these findings support the usefulness and effectiveness of zinc oxide nanofertilizer and laser irradiation treatment to enhance the growth and yield of sweet basil plants. The article presents some promising patents on ZnO nanofertilizer and He Ne laser irradiation. PMID- 24215470 TI - Survey of calcium supplementation to prevent preeclampsia: the gap between evidence and practice in Brazil. AB - BACKGROUND: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide and especially in Latin America. High quality evidence indicates that calcium supplementation during pregnancy significantly reduces the incidence of preeclampsia and its consequences, including severe maternal morbidity and death. Few studies have assessed the implementation of this intervention in clinical practice. The study aimed to assess the proportion of pregnant women who received calcium supplements in Brazilian public antenatal care clinics. METHODS: This cross-sectional study interviewed women waiting for antenatal care visits in 9 public clinics in 4 Brazilian cities in 2010-2012. Trained interviewers used a standardized anonymous questionnaire to collect socio demographic and obstetric data, information on ingestion of dairy products and on prescriptions received during current pregnancy. RESULTS: A total of 788 valid questionnaires were analyzed. Participants were young (mean age 25.9), mostly multiparous (71.3%) and in the 2nd or 3rd trimesters of pregnancy at the time of interview (87.6%). Only 5.1% (40/788) had received a prescription for calcium supplements. Based on their reported ingestion of dairy products, the mean daily dietary calcium intake of the participants was 210 (+ 265) mg/day and over 90% consumed less than 1 g of calcium/day. CONCLUSIONS: Despite good quality evidence indicating the benefits of this practice especially for women with low calcium diets, less than 6% of a sample of women receiving antenatal care in Brazilian public clinics received a prescription for calcium supplements. There is an urgent need to upscale the implementation of this life-saving intervention. PMID- 24215472 TI - The effect of 0.5% tropicamide/0.5% phenylephrine mixed eye drop in Chinese adults with myopia and its inter-eye difference in refractive outcomes. AB - OBJECTIVE: To evaluate the effect of 0.5% tropicamide/0.5% phenylephrine mixed eye drop and make the inter-eye comparison of refractive outcomes in Chinese adults with myopia. METHODS: Refractive measurements were performed without cycloplegia and repeated 30 minutes later with 0.5% tropicamide/0.5% phenylephrine mixed eye drop (Mydrin-P*) on 341 myopic adults. Vector analysis was used to analyze the data. Changes of spherical equivalent (M) and astigmatism for both J0 and J45 components between these two refractions were calculated as Error_M, Error_J0 and Error_J45. Inter-eye correlations were studied. The inter eye difference after cycloplegics were described as Diff M, Diff J0 and Diff J45. The effect of anisometropia, age and the higher order aberrations (HOAs) on inter eye differences toward the cycloplegic agent were analyzed. RESULTS: Difference was found only for the Error_J45 component between the two eyes (p=0.0040). Pearson correlation coefficients between the two eyes for Error_M, Error_J0, and Error_J45 were 0.3140 (p<0.0001), 0.1464 (p=0.0068), and 0.0099 (p=0.8558), respectively. The inter-eye differences (Diff) in response to cycloplegic agent increased with the amount of anisometropia. The oldest group had the highest Diff M values. However, HOAs were found not to be related to the inter-eye differences. CONCLUSIONS: Accommodation was still relaxed by tropicamide/phenylephrine eye drops in myopic adults. The changes of refraction due to cycloplegia were not well correlated between the two eyes in myopic patients. Anisometropia and ocular dominance might be an important factor for the inter-eye difference. PMID- 24215473 TI - Combating multidrug-resistant Gram-negative bacterial infections. AB - INTRODUCTION: Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged as one of the world's greatest health threats. The development of novel antibiotics to treat MDR Gram-negative bacteria has, however, stagnated over the last half century. AREAS COVERED: This review provides an overview of recent R&D activities in the search for novel antibiotics against MDR Gram-negatives. It provides emphasis in three key areas. First, the article looks at new analogs of existing antibiotic molecules such as beta-lactams, tetracyclines, and aminoglycoside as well as agents against novel bacterial targets such as aminoacyl-tRNA synthetase and peptide deformylase. Second, it also examines alternative strategies to conventional approaches including cationic antimicrobial peptides, siderophores, efflux pump inhibitors, therapeutic antibodies, and renewed interest in abandoned treatments or those with limited indications. Third, the authors aim to provide an update on the current clinical development status for each drug candidate. EXPERT OPINION: The traditional analog approach is insufficient to meet the formidable challenge brought forth by MDR superbugs. With the disappointing results of the genomics approach for delivering novel targets and drug candidates, alternative strategies to permeate the bacterial cell membrane, enhance influx, disrupt efflux, and target specific pathogens via therapeutic antibodies are attractive and promising. Coupled with incentivized business models, governmental policies, and a clarified regulatory pathway, it is hoped that the antibiotic pipeline will be filled with an effective armamentarium to safeguard global health. PMID- 24215474 TI - Relaxometry studies of a highly stable nanoscale metal-organic framework made of Cu(II), Gd(III), and the macrocyclic DOTP. AB - The macrocyclic ligand DOTP is used to assemble a porous, heterometallic metal organic framework (MOF). This MOF is miniaturizable down to the nanoscale to form stable colloids, is stable in physiological saline solution and cell culture media, and is not cytotoxic. It shows interesting relaxometric properties with r1 at high field (500 MHz) of 5 mM(-1).s(-1) and a maximum r1 = 15 mM(-1).s(-1) at 40 MHz, which remains constant over a wide pH range and increases with temperature. PMID- 24215475 TI - Topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid: randomized controlled trial with six months follow-up. AB - BACKGROUND: Topical 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) with some transient adverse events. OBJECTIVE: The purpose of the study was to evaluate the efficacy and side effects of two different light doses when treating AKs with ALA-PDT on the face/scalp. METHODS: Thirty-eight patients with two histologically confirmed AKs were enrolled in the within-patient comparison study. ALA-PDT was performed twice with two weeks interval for each AK. Patients were randomized to receive a light dose of 70 or 100 J/cm2 as their first split face/scalp treatment. Follow-up examinations were carried out at months 3 and 6. Efficacy end point included clinical/histological AK clearance rate. RESULTS: No significant difference in therapeutic efficacy and adverse events of ALA-PDT was found between the two light doses at both follow-up visits. At months 3 and 6 after PDT the RATE of complete remission were respectively 100% and 92.1% for 70 J/cm2, 92.1% and 84.2% for 100 J/cm2. The adverse events of the treatment were rosacea 5/76 (6.58%), hyperpigmentation 4/76 (5.26%), hypopigmentation 4/76 (5.26%), transient milia 3/76 (3.95%). CONCLUSIONS: The topical ALA-PDT with the red light dose of 70 J/cm2 is an effective treatment for mild and moderate AKs on the face/scalp with expected adverse events of pigmentation changes, rosacea and transient milia. PMID- 24215476 TI - Dentinogenesis imperfecta - hardness and Young's modulus of teeth. AB - Dentinogenesis imperfecta type II (DI-II) is the most common dental genetic disease with reported incidence 1 in 8000. Elasticity and hardness of the enamel of teeth are important values which are connected with their resistance to attrition. It is hypothesized that values of physical properties for healthy teeth and teeth with DI-II are different. The aim of the study was to investigate some physical properties of teeth extracted from patients with DI-II in comparison with normal teeth. The material of the study was six teeth: three lower molars, with clinical signs of DI-II, which were extracted due to complications of pulp inflammation and three other lower molars which were extracted for orthodontic reasons - well formed, without any signs of pathology. The surfaces of DI-II and normal teeth were tested on the CSM Instruments Scratch Tester machine (producer CSEM Switzerland) by Oliver and Pharr method. The indenter used was Vicker's VG-73 diamond indenter. Additionally, the Scanning Electron Microscopy (SEM) analysis of the surface of the teeth with DI-II was made. Vickers hardness of the teeth with dental pathology (DI-II) was seven times smaller, and Young's modulus six times smaller than those of healthy teeth. The parameters of hardness and elasticity of enamel of teeth with clinical diagnosis of DI-II were very much smaller than in normal teeth and because of that can be responsible for attrition. PMID- 24215477 TI - Validation of conventional fluoroscopic and ECG criteria for right ventricular pacemaker lead position using cardiac computed tomography. AB - INTRODUCTION: It is hypothesized that pacing the right ventricular (RV) septum is associated with less deleterious outcomes than RV apical pacing. Our aim was to validate fluoroscopic and electrocardiography (ECG) criteria for describing pacemaker and implantable cardioverter defibrillator RV "septal" lead position against the proposed gold standard: cardiac computed tomography (CT). METHODS: Using the conventional fluoroscopic criteria, we intended to place RV nonapical leads on the interventricular septum. Lead positions were later retrospectively analyzed with CT and correlated with ECGs and fluoroscopic projections: posterior anterior, 40 degrees left anterior oblique (LAO), 40 degrees right anterior oblique (RAO), and left lateral. RESULTS: Only 21% (nine of 35) of presumed "septal" RV nonapical leads using the conventional fluoroscopic criteria were on the true septum. A schema developed to define septal position in the RAO fluoroscopic view had high agreement with CT images. ECG criteria had only fair to moderate agreement with CT. The paced QRS duration was significantly longer (P < 0.001) with RV apical pacing (176 +/- 10.7 ms), compared to RV nonapical pacing (144.5 +/- 14.3 ms). CONCLUSION: Using the conventional fluoroscopic criteria, only a minority of RV leads were implanted on the true RV septum. Instead, aiming for the middle of the cardiac silhouette in the RAO fluoroscopic view, confirming rightward orientation in the LAO view, and having a paced QRS duration <140 ms may allow the implanting cardiologist a simple, more accurate method to achieve true RV septal lead positioning. PMID- 24215478 TI - Self-assembly and bilayer-micelle transition of fatty acids studied by replica exchange constant pH molecular dynamics. AB - Recent interest in the development of surfactant-based nanodelivery systems targeting tumor sites has sparked our curiosity in understanding the detailed mechanism of the self-assembly and phase transitions of pH-sensitive surfactants. Toward this goal, we applied a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with the hybrid-solvent scheme and pH based replica-exchange protocol, to study the de novo self-assembly of 30 and 40 lauric acids, a simple model titratable surfactant. We observed the formation of a gel-state bilayer at low and intermediate pH and a spherical micelle at high pH, with the phase transition starting at 20-30% ionization and being completed at 50%. The degree of cooperativity for the transition increases from the 30-mer to the 40-mer. The calculated apparent or bulk pKa value is 7.0 for the 30-mer and 7.5 for the 40-mer. Congruent with experiment, these data demonstrate that CpHMD is capable of accurately modeling large conformational transitions of surfactant systems while allowing the simultaneous proton titration of constituent molecules. We suggest that CpHMD simulations may become a useful tool in aiding in the design and development of pH-sensitive nanocarriers for a variety of biomedical and technological applications. PMID- 24215479 TI - High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network. AB - The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT. PMID- 24215481 TI - Occupations, habits, and routines: perspectives from persons with diabetes. AB - CONTEXT: Almost all of the management of diabetes is the direct responsibility of the person with diabetes. While many studies have attempted to examine issues of management of diabetes and compliance with medical recommendations, little has been done to examine daily diabetic care from an occupational perspective. The purpose of this research was to examine and describe how persons with diabetes perceive the occupations related to the management of their diabetes. METHODS: A qualitative methods approach was used including photo elicitation and interviews. A team of student researchers recruited participants for a sample of convenience. RESULTS: The following themes emerged from qualitative cross-case analysis: "Changes over time"; "What to eat"; "Habits and routines"; and "Family: Occupational impacts". DISCUSSION: Findings highlight the importance of considering the individual experience of diabetes self-management occupations and the need to develop habits and routines to support management of diabetes. Further research is needed to expand our understanding of how daily routines and habits can affect health in persons with diabetes. PMID- 24215480 TI - Hydrogen exchange-mass spectrometry measures stapled peptide conformational dynamics and predicts pharmacokinetic properties. AB - Peptide drugs have traditionally suffered from poor pharmacokinetic properties due to their conformational flexibility and the interaction of proteases with backbone amide bonds. "Stapled Peptides" are cyclized using an all-hydrocarbon cross-linking strategy to reinforce their alpha-helical conformation, yielding improved protease resistance and drug-like properties. Here we demonstrate that hydrogen exchange-mass spectrometry (HX-MS) effectively probes the conformational dynamics of Stapled Peptides derived from the survivin-borealin protein-protein interface and predicts their susceptibility to proteolytic degradation. In Stapled Peptides, amide exchange was reduced by over five orders-of-magnitude versus the native peptide sequence depending on staple placement. Furthermore, deuteration kinetics correlated directly with rates of proteolysis to reveal the optimal staple placement for improved drug properties. PMID- 24215483 TI - Evaluation of ocular surface temperature in patients with pterygium. AB - PURPOSE: To investigate ocular surface temperature in eyes with pterygium and dry eye disease. METHODS: Eighteen eyes of 18 patients with pterygium (group 1), 18 eyes of 18 patients diagnosed with dry eye disease (group 2), and 22 eyes of 22 healthy subjects with no signs of dry eye (group 3), were included in this prospective study. Schirmer's test I and II, and tear film break up time (BUT) were evaluated. Infrared thermal imaging (Tomey TG 1000, Tomey Corp, Nagoya, Japan) was used to study the temperature of the ocular surface. All measurements were performed by one examiner only. RESULTS: No significant difference in temperature course over ten seconds of eye opening was present between groups 1 and 2 (p=0.551). However, a significant difference was present between groups 1 and 3 (p=0.001) and between groups 2 and 3 (p=0.003). Comparing group 1 and group 2, statistically significant differences in Schirmer's test I (p<0.001) and II (p<0.001) and BUT (p=0.04) were present. There were also significant differences in Schirmer's test I (p<0.001) and II (p<0.001) and BUT (p<0.001) between group 2 and group 3. No significant difference in Schirmer's test I (p=0.785) and II (p=0.871) was present between group 1 and group 3. However, a statistically significant difference in BUT was noted (p<0.001). CONCLUSION: During sustained eye opening, a significant decrease in corneal surface temperature occurred in eyes with pterygium and dry eye disease. Thermography, in addition to other investigations, might be used to objectively identify dry eye symptoms in patients with pterygium. In addition to cosmetic appearance, increasing astigmatism, and expanding growth towards the center of the cornea, this new supplementary data may help to determine the proper time for intervention. PMID- 24215482 TI - Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors. AB - We present "one-step application" dissolving and hydrogel-forming microneedle arrays (MN) for enhanced delivery of photosensitizers/precursors. MN (280 MUm) prepared from 20% w/w poly(methylvinylether/maelic acid) and cross-linked with glycerol by esterification to form hydrogels upon skin insertion, or allowed to dissolve rapidly in skin, were combined with patches containing 19 mg cm(-2) of 5 aminolevulinic acid (ALA) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) for drug delivery. Both MN types were mechanically robust, with compression forces of 20.0 N only causing height reductions of 14%. Application forces as low as 8.0 N per array allowed >95% of the MN in each array type to penetrate excised porcine skin, with the MN penetrating to approximately 220 MUm. MN significantly enhanced transdermal delivery of ALA and TMP in vitro, with the hydrogel-forming system comparable with the dissolving system for ALA delivery (approximately 3000 nmol cm(-2) over 6 h), but superior for delivery of the much larger TMP molecule (approximately 14 nmol cm(-2) over 24 h, compared to 0.15 nmol cm(-2)). As this technology clearly has potential in enhanced photodynamic therapy of neoplastic skin lesions, we are currently planning animal studies, to be followed by preliminary human evaluations. GMP manufacturing scale-up is ongoing. PMID- 24215484 TI - Broadband optical modulators based on graphene supercapacitors. AB - Optical modulators are commonly used in communication and information technology to control intensity, phase, or polarization of light. Electro-optic, electroabsorption, and acousto-optic modulators based on semiconductors and compound semiconductors have been used to control the intensity of light. Because of gate tunable optical properties, graphene introduces new potentials for optical modulators. The operation wavelength of graphene-based modulators, however, is limited to infrared wavelengths due to inefficient gating schemes. Here, we report a broadband optical modulator based on graphene supercapacitors formed by graphene electrodes and electrolyte medium. The transparent supercapacitor structure allows us to modulate optical transmission over a broad range of wavelengths from 450 nm to 2 MUm under ambient conditions. We also provide various device geometries including multilayer graphene electrodes and reflection type device geometries that provide modulation of 35%. The graphene supercapacitor structure together with the high-modulation efficiency can enable various active devices ranging from plasmonics to optoelectronics. PMID- 24215485 TI - A simplified combination antiretroviral therapy regimen enhances adherence, treatment satisfaction and quality of life: results of a randomized clinical trial. AB - OBJECTIVES: The aim of the study was to investigate the effect of a simplified regimen, in terms of reducing pill burden, dietary requirements and possible adverse effects, on patients' adherence, treatment satisfaction and quality of life (QoL). METHODS: Antiretroviral-naive patients who achieved a viral load < 50 HIV-1 RNA copies/ml after induction therapy with twice-daily (bid) lopinavir/ritonavir (LPV/r) and fixed-dose zidovudine (ZDV)/lamivudine (3TC) (CBV) were randomly assigned to continue CBV/LPV/r or switch to fixed-dose ZDV/3TC/abacavir (TZV). Patients completed standardized questionnaires on adherence, treatment satisfaction and QoL at randomization (between weeks 12 and 24) and at weeks 48, 72 and 96. RESULTS: Patients on CBV/LPV/r were more likely to have skipped medicines in the last week (P = 0.035) and during the preceding weekend (P = 0.027) than patients on TZV. Patients on CBV/LPV/r were significantly less satisfied with the convenience of their treatment (P = 0.004) and tended to be less satisfied with the side effects of their treatment (P = 0.091) and continuation of their present treatment (P = 0.056) than patients on TZV. Patients on CBV/LPV/r reported significantly lower levels of role functioning (P = 0.013) than patients on TZV. CONCLUSIONS: In this randomized controlled trial, simplification of therapy to fixed-dose TZV among patients with suppressed HIV RNA was perceived to be more convenient, and resulted in improved adherence and better role functioning, than continuing treatment with CBV/LPV/r. PMID- 24215486 TI - Suppression of allergic reactions in ovalbumin-sensitized mice by yam storage proteins dioscorins. AB - To study the biomedical functions of dioscorins isolated from various species of Dioscorea , we investigated their antiallergic potential using an OVA-induced allergy mouse model. All the dioscorins suppressed allergic reactions by decreasing the serum IgE and histamine levels. The serum IFN-gamma and IgG2a levels increased in all the dioscorin-treated mice. The spleen cells from the dioscorin-treated mice also exhibited an up-regulation of IFN-gamma secretion in response to ConA stimulation. Although dioscorins did not affect the IgG1 levels, the IL-5 levels decreased to basal levels in mice treated with dioscorins of D. alata or D. japonica and in most of the lymphoid cells of the dioscorin-treated mice in response to ConA stimulation. The decrease of IgE and histamine levels was concomitant with an increase in IFN-gamma and IgG2a levels and with a decrease in IL-5 levels, suggesting that dioscorins suppressed the OVA-induced allergic reactions, possibly through modulating an imbalanced Th1/Th2 immune response. PMID- 24215487 TI - Human herpesvirus-6A gQ1 and gQ2 are critical for human CD46 usage. AB - Based on genetic and antigenic differences and on their cell tropism, human herpes virus-6 (HHV-6) has been classified into two variants, HHV-6A and HHV-6B. Recently, these variants were re-classified as two different species. The HHV-6A glycoprotein complex, gH/gL/gQ1/gQ2 binds to its cellular receptor, CD46; however, the corresponding complex in HHV-6B rarely binds to CD46. To determine which viral molecules in the glycoprotein complex determine HHV-6A-CD46 binding, each molecule of the HHV-6A complex (i.e., gH, gL, gQ1, or gQ2) was replaced with the corresponding HHV-6B molecule, and the ability of the replaced protein to be incorporated into the complex and the ability of the complex to bind CD46 were examined. It was found that when all four glycoproteins were expressed, they were able to form a tetrameric complex. However, a complex formed by HHV-6A gH/gL/gQ1/gQ2 complexes replaced with HHV-6B gQ1 or gQ2 scarcely bind CD46, whereas HHV-6A complexes in which gH or gL was replaced with the HHV-6B molecules did bind it. These results indicate that HHV-6A gQ1 and gQ2 play an important role in CD46 binding. PMID- 24215488 TI - Osteopontin is a prognostic biomarker in non-small cell lung cancer. AB - BACKGROUND: In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed. METHODS: Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated. RESULTS: High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome. CONCLUSIONS: OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection. PMID- 24215489 TI - Two new 20alpha(H)-ursane-type triterpenoids from Ilex cornuta and their cytotoxic activities. AB - Two new 20alpha-ursane-type triterpenoids (1-2) were isolated from the roots of Ilex cornuta, along with three known triterpenoids (3-5). The structures of compounds 1-2 were determined as 3beta, 23-dihydroxy-20alpha(H)-urs-12-en-28-oic acid (1), 3beta,19alpha,23-trihydroxy-20alpha(H)-urs-12-en-28-oic acid 3beta-O alpha-l-arabinopyranoside (2), on the basis of hydrolysis and spectral evidence, including 1D- and 2D-NMR and high-resolution electrospray ionization mass spectrometry analyses. These pure isolates (1-5) were tested for their cytotoxic activities by MTT assay. PMID- 24215490 TI - Acrodermatitis continua of Hallopeau (ACH): two cases successfully treated with adalimumab. AB - Acrodermatitis continua of Hallopeau (ACH), also known as dermatitis repens or acrodermatitis perstans, is a rare acropustular eruption, characterized by sterile pustules, paronychia and atrophic skin changes, onychodystrophy and osteolysis of the distal phalanges of the fingers and toes. While some consider ACH a distinct entity, many believe it to be a variant of pustular psoriasis, especially as cases of ACH progressing to generalized pustular psoriasis. The treatment options used are various; however, its typical cyclic recurrences, which induce important physical and psychological morbidity, may render this pathology difficult to treat. Hence, it was considered important to review the evolution of treatment options available thus far including use of biologics. Hereby, we report two patients with ACH who were successfully treated with adalimumab. By analogy to the efficacy of TNF-alpha antagonists in the treatment of generalized pustular psoriasis, the two patients we report illustrate the long term efficacy and safety of adalimumab in the treatment of Hallopeau's acrodermatitis refractory to therapies. PMID- 24215491 TI - Identification of Swedish mosquitoes based on molecular barcoding of the COI gene and SNP analysis. AB - Mosquito-borne infectious diseases are emerging in many regions of the world. Consequently, surveillance of mosquitoes and concomitant infectious agents is of great importance for prediction and prevention of mosquito-borne infectious diseases. Currently, morphological identification of mosquitoes is the traditional procedure. However, sequencing of specified genes or standard genomic regions, DNA barcoding, has recently been suggested as a global standard for identification and classification of many different species. Our aim was to develop a genetic method to identify mosquitoes and to study their relationship. Mosquitoes were captured at collection sites in northern Sweden and identified morphologically before the cytochrome c oxidase subunit I (COI) gene sequences of 14 of the most common mosquito species were determined. The sequences obtained were then used for phylogenetic placement, for validation and benchmarking of phenetic classifications and finally to develop a hierarchical PCR-based typing scheme based on single nucleotide polymorphism sites (SNPs) to enable rapid genetic identification, circumventing the need for morphological characterization. The results showed that exact phylogenetic relationships between mosquito taxa were preserved at shorter evolutionary distances, but at deeper levels, they could not be inferred with confidence using COI gene sequence data alone. Fourteen of the most common mosquito species in Sweden were identified by the SNP/PCR-based typing scheme, demonstrating that genetic typing using SNPs of the COI gene is a useful method for identification of mosquitoes with potential for worldwide application. PMID- 24215492 TI - Osmolyte effects on the self-association of concanavalin A: testing theoretical models. AB - The formation and stability of protein-protein interfaces are of obvious biological importance. While a large body of literature exists describing the effect of osmolytes on protein folding, very few studies address the effect of osmolytes on protein association and binding. The plant lectin concanavalin A (ConA), which undergoes a reversible tetramer-to-dimer equilibrium as a function of pH, was used as a model system to investigate the influence of nine osmolytes on protein self-association. The stabilizing or destabilizing impacts of the osmolytes were evaluated from pH titrations combined with circular dichroism spectroscopy. Relative to the dimer, trimethylamine N-oxide, betaine, proline, sarcosine, sorbitol, sucrose, and trehalose all stabilized the ConA tetramer to varying extents. Glycerol had a negligible effect, and urea destabilized the tetramer. From multiple titrations in different osmolyte concentrations, an m value (a thermodynamic parameter describing the change in the association free energy per molar of osmolyte) was determined for each osmolyte. Experimental m values were compared with those calculated using two theoretical models. The Tanford transfer model, with transfer free energies determined by Bolen and co workers, failed to accurately predict the m-values in most cases. A model developed by Record and co-workers, currently applicable only to urea, betaine, and proline, more accurately predicted our experimental m-values, but significant discrepancies remained. Further theoretical work is needed to develop a thermodynamic model to predict the effect of osmolytes on protein-protein interfaces, and further experimental work is needed to determine if there is a general stabilization by osmolytes of such interfaces. PMID- 24215493 TI - Reversible actuation of polyelectrolyte films: expansion-induced mechanical force enables cis-trans isomerization of azobenzenes. AB - Fabrication of light-driven actuators that can prolong their deformation without constant irradiation poses a challenge. This study shows the preparation of polymeric actuators that are capable of reversible bending/unbending movements and prolonging their bending deformation without UV irradiation by releasing thermally cross-linked azobenzene-containing polyelectrolyte films with a limited free volume from substrates. Layer-by-layer assembly of poly{1-4[4-(3-carboxy-4 hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl sodium salt} (PAZO) poly(acrylic acid) (PAA) complexes (noted as PAZO-PAA) with poly(allylamine hydrochloride) (PAH) produces azobenzene-containing PAZO-PAA/PAH films. UV irradiation induces trans-cis isomerization of azobenzenes and allows large-scale bending deformation of the actuators. The actuators prolong the bending deformation even under visible light irradiation because the cis-trans back isomerization of azobenzenes is inhibited by the limited free volume in the actuators. Unbending of actuators is attained by exposing the actuators to a humid environment at room temperature. Film expansion in a humid environment produces a mechanical force that is sufficiently strong to enable the cis-trans back isomerization of azobenzenes and restore the bent actuators to their original configuration. The capability of the force produced by film expansion for cis-trans azobenzene isomerization can be helpful for designing novel polymeric actuators. PMID- 24215494 TI - Detection and quantification of montmorillonite nanoclay in water-ethanol solutions by graphite furnace atomic absorption spectrometry. AB - Organo-modified montmorillonite (O-MMT) was detected in various water-ethanol solutions by using graphite furnace atomic absorption spectrometry, based on the simultaneous elemental analysis of silicon (Si) and aluminium (Al). The quantification limits of the method were 0.03 mg L-1 for Si and 0.01 mg L-1 for Al, but can be improved to 8 MUg L-1 for Si and 3 MUg L-1 by using the concentration function of the instrument. A stability test of O-MMT in suspension was conducted by considering the solvent type (i.e., water and/or ethanol) and a surfactant. A good dispersion of O-MMT was achieved in suspensions with water and ethanol at 1:2 (v/v) or with pure ethanol, while the addition of a surfactant improved the dispersion of O-MMT in water. The Si and Al concentrations in the suspensions were correlated with O-MMT concentrations. The Si and Al contents in the O-MMT were determined by using graphite furnace atomic absorption spectrometry to be 22% +/- 1.1% and 9.3% +/- 0.5% wt/wt, respectively, which was in agreement with values obtained by X-ray fluorescence spectrometry method performed in this study. PMID- 24215495 TI - Risk factors for conversion from unipolar psychotic depression to bipolar disorder. AB - OBJECTIVES: Patients with unipolar psychotic depression (PD) are at high risk of developing bipolar disorder (BD). This conversion has important implications for the choice of treatment. This study, therefore, aimed to identify risk factors associated with diagnostic conversion from PD to BD. METHODS: We conducted a population-based, historical prospective cohort study by merging data from Danish registers. Patients assigned an ICD-10 diagnosis of PD between 1 January 1995 and 31 December 2007 were identified in the Danish Central Psychiatric Research Register and were followed until the development of BD, death, loss to follow-up, or 31 December 2007. Potential risk factors for conversion to BD, also defined through various Danish registers, were tested in multiple logistic regression analyses with risk expressed as adjusted odds ratios (AOR). RESULTS: We identified 8,588 patients with PD, of whom 609 (7.1%) developed BD during follow up. The following characteristics were significantly associated with diagnostic conversion from PD to BD: early onset of PD [AOR = 0.99 (per year of increasing age), p = 0.044], recurrent depression [AOR = 1.02 (per episode), p = 0.036], living alone (AOR = 1.29, p = 0.007), receiving a disability pension (AOR = 1.55, p < 0.001), and the highest educational level being a technical education (AOR = 1.55, p < 0.001), short-cycle higher education (AOR = 2.65, p < 0.001), or medium cycle higher education (AOR = 1.75, p < 0.001). CONCLUSIONS: Diagnostic conversion to BD was prevalent among patients with PD. The following characteristics were significantly associated with this conversion: early onset of PD, recurrent depression, living alone, receiving a disability pension, and the highest educational level being a technical education, short-cycle higher education, or medium-cycle higher education. PMID- 24215496 TI - Enhancing the performance of solution-processed bulk-heterojunction solar cells using hydrogen-bonding-induced self-organization of small molecules. AB - Small-molecule solar-cell performance is highly sensitive to the crystallinity and intermolecular connectivity of the molecules. In order to enhance the crystallinity for the solution-processed small molecule, it is possible to make use of carboxylic acid end-functional groups to drive hydrogen-bonding-induced pi pi stacking of conjugated molecules. Herein, we report the synthesis and characterization of quarterthiophenes with carboxylic acid as end groups. The formation of hydrogen bonds between neighboring acid groups gives rise to a pseudo-polymeric structure in the molecules, which leads to substantial improvement in the organization and crystallinity of the active layers. This resulted in a four-fold increase in the hole mobility and a two-fold improvement in the performance of the solar cell device for the acid-functionalized molecule, compared to its ester analogue. More importantly, optimal device performance for the acid-functionalized molecule was achieved for the as-cast film, thereby reducing the reliance on thermal annealing and solvent additives. PMID- 24215497 TI - Appearance concerns and psychosocial adjustment following head and neck cancer: A cross-sectional study and nine-month follow-up. AB - Psychosocial difficulties have been reported in head and neck cancer (HNC) patients, yet only few studies have assessed the impact of altered appearance following HNC treatment using theoretically selected measures of appearance related distress. This study investigated appearance-related adjustment following HNC, and demographic and socio-cognitive predictors of adjustment. HNC patients (n=49) completed baseline questionnaires and a nine-month postal follow-up (n=20). Participants showed considerable variation in appearance-related adjustment, with females reporting higher levels of appearance-related distress (derriford appearance scale [DAS-24]) than females in the general population and male HNC survivors. Depression scores on the hospital anxiety and depression scale were higher than UK norms whilst anxiety was similar to UK norms. There were no significant differences between baseline and follow-up data. Fear of negative evaluation (a central feature of social anxiety) was a significant predictor of appearance-related adjustment at baseline, whilst dispositional optimism was a significant predictor of appearance-related adjustment at baseline and follow-up. Qualitative responses showed themes of appearance and disability, and coping strategies. Findings suggest that appearance-related adjustment post HNC varies considerably and psychosocial services working with HNC patients should consider this broad pattern of response. Future research to examine the role of socio-cognitive predictors of appearance-related adjustment could progress development of effective psychological interventions. PMID- 24215498 TI - Infection with Haemoproteus iwa affects vector movement in a hippoboscid fly- frigatebird system. AB - Haemosporidian parasites, which require both a vertebrate and invertebrate host, are most commonly studied in the life stages occurring in the vertebrate. However, aspects of the vector's behaviour and biology can have profound effects on parasite dynamics. We explored the effects of a haemosporidian parasite, Haemoproteus iwa, on a hippoboscid fly vector, Olfersia spinifera. Olfersia spinifera is an obligate ectoparasite of the great frigatebird, Fregata minor, living among bird feathers for all of its adult life. This study examined the movements of O. spinifera between great frigatebird hosts. Movement, or host switching, was inferred by identifying host (frigatebird) microsatellite genotypes from fly bloodmeals that did not match the host from which the fly was collected. Such host switches were analysed using a logistic regression model, and the best-fit model included the H. iwa infection status of the fly and the bird host sex. Uninfected flies were more likely to have a bird genotype in their bloodmeal that was different from their current host's genotype (i.e. to have switched hosts) than infected flies. Flies collected from female birds were more likely to have switched hosts than those collected on males. Reduced movement of infected flies suggests that there may be a cost of parasitism for the fly. The effect of host sex is probably driven by differences in the sex ratio of bird hosts available to moving flies. PMID- 24215499 TI - Determination of optimal cyclic uniaxial stretches for stem cell-to-tenocyte differentiation under a wide range of mechanical stretch conditions by evaluating gene expression and protein synthesis levels. AB - We examined optimal cyclic uniaxial stretches for stem cell-to-tenocyte differentiation by applying a wide range of cyclic mechanical stimuli. Human bone marrow mesenchymal stem cells (hBMSCs) were subjected to three types of cyclic elongation of 5%, 10%, or 15% at a cyclic frequency of 1 Hz for 24 h or 48 h, and differentiation into tenocytes was assessed by two methods: real-time polymerase chain reaction determination of gene expression levels and western blotting analysis of protein expression levels. The gene expression levels of the differentiation markers type I collagen (Col I), type III collagen (Col III), tenascin-C (Tnc), and scleraxis (Scx), all of which are constituents of tendon tissue, were increased when cells were exposed to 10% stretching stimulation. The levels of Col I and Tnc protein synthesis levels were also higher in the cells with 10% stretching stimulation than in those subjected to other stimuli. The results indicated that 10% stretching stimulus was efficient to induce the differentiation of hBMSCs into tenocytes. In addition, the changes in gene and protein expression levels were strongly correlated with cell orientation angle. The results presented here suggest that mesenchymal stem cell-to-tenocyte differentiation is strongly associated with cumulative elongation load on the cells. This work provides novel insights into the differentiation of tenogenesis in a strain-induced environment and supports the therapeutic potential of hBMSCs. PMID- 24215500 TI - Absence of Ce3+ sites in chemically active colloidal ceria nanoparticles. AB - The catalytic performance of ceria nanoparticles is generally attributed to active sites on the particle surface. The creation of oxygen vacancies and thus nonstoichiometric CeO(2-delta) has been proposed to result in Ce(3+) sites with unpaired f electrons which can be oxidized to spinless Ce(4+) ions during catalytic reactions. We monitored the Ce electronic structure during the synthesis and catalase mimetic reaction of colloidal ceria nanoparticles under in situ conditions. By means of high-energy resolution hard X-ray spectroscopy, we directly probed the Ce 4f and 5d orbitals. We observe pronounced changes of the Ce 5d bands upon reduction of the particle size and during the catalytic reaction. The Ce 4f orbitals, however, remain unchanged, and we do not observe any significant number of spin-unpaired Ce(3+) sites even for catalytically active small (3 nm) particles with large surface to bulk ratio. This confirms strong orbital mixing between Ce and O, and the Ce spin state is conserved during the reaction. The particles show an increase of the interatomic distances between Ce and O during the catalytic decomposition of hydrogen peroxide. The redox partner is therefore not a local Ce(3+) site, but the electron density that is received and released during the catalytic reaction is delocalized over the atoms of the nanoparticle. This invokes the picture of an electron sponge. PMID- 24215501 TI - An approach to facilitate healthcare professionals' readiness to support technology use in everyday life for persons with dementia. AB - Everyday technologies (ETs) like microwave ovens and automatic telephone services as well as assistive technologies (ATs) are often used in the performance of everyday activities. As a consequence, the ability to manage technology is important. This pilot study aimed to clarify the applicability of a model for knowledge translation to support healthcare professionals, to support technology use among older adults with dementia and their significant others. An additional aim was to explore the process of translating the model into practice. The applicability of the model (comprising a one-day course, including introduction and provision of tools, followed by interviews during and after a period of practice) was clarified for 11 healthcare professionals using a constant comparative approach. The content of the model gave the participants an eye opening experience of technology use among persons with dementia. They also described how they had incorporated the model as a new way of thinking which supported and inspired new investigations and collaborations with colleagues and significant others. This study provided an applicable model of how research knowledge about technology use can be translated into clinical practice and be used by healthcare professionals to support the use of technology for persons with dementia. PMID- 24215502 TI - Assessment of nonsteroidal anti-inflammatory drug-induced cardiotoxicity. AB - INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (coxibs) and traditional NSAIDs (tNSAIDs), have been widely used for the treatment of pain and rheumatic disease. The use of NSAIDs has been linked to increased cardiovascular toxicity in both healthy individuals and patients with established cardiovascular disease. Various recently published studies have raised concerns about the cardiovascular safety of NSAIDs; this review is focused on the cardiotoxic effects of NSAIDs. AREAS COVERED: This review focuses on arthritis trials, placebo-controlled trials, meta-analyses, preclinical and observational studies associated with the use of NSAIDs-induced cardiotoxicity. It analyses the data given in these studies and discusses the cardiotoxic risk of NSAIDs. EXPERT OPINION: Analysis of various clinical, preclinical, meta-analysis and observational studies showed that coxibs and tNSAIDs increase the risk of cardiotoxicity. Cardiotoxic risk depends on dose, duration and frequency of NSAID administration. Most studies were based on large medical databases with miscellaneous populations and pointed to an increase risk of cardiotoxicity under NSAID medication. The cardiotoxicity associated with use of NSAIDs might be due to inhibition of prostacyclin synthesis, oxidative stress, increase in blood pressure and impaired endothelial function. PMID- 24215503 TI - Leaf cuticular lipids on the Shandong and Yukon ecotypes of saltwater cress, Eutrema salsugineum, and their response to water deficiency and impact on cuticle permeability. AB - The impact of water-deficit stress on leaf cuticular waxes and cutin monomers, and traits associated with cuticle permeability were examined in Shandong and Yukon ecotypes of Eutrema salsugineum (syn. Thellungiella salsuginea). Although Shandong exhibits glaucous leaves, and Yukon is non-glaucous, wax amounts on non stressed Yukon leaves were 4.6-fold higher than on Shandong, due mainly to Yukon's eightfold higher wax fatty acids, especially the C22 and C24 acid homologues. Water deficit caused a 26.9% increase in total waxes on Shandong leaves, due mainly to increased C22 and C24 acids; and caused 10.2% more wax on Yukon, due mainly to an increase in wax alkanes. Total cutin monomers on non stressed leaves of Yukon were 58.3% higher than on Shandong. Water deficit caused a 28.2% increase in total cutin monomers on Shandong, whereas total cutin monomers were not induced on Yukon. With or without stress, more abundant cuticle lipids were generally associated with lower water loss rates, lower chlorophyll efflux rates and an extended time before water deficit-induced wilting. In response to water deficit, Shandong showed elevated transcription of genes encoding elongase subunits, consistent with the higher stress induction of acids by Shandong. Yukon's higher induction of CER1 and CER3 transcripts may explain why alkanes increased most on Yukon after water deficit. Eutrema, with its diverse cuticle lipids and responsiveness, provides a valuable genetic resource for identifying new genes and alleles effecting cuticle metabolism, and lays groundwork for studies of the cuticle's role in extreme stress tolerance. PMID- 24215504 TI - Effects of three commonly used anesthetics on intraocular pressure in mouse. AB - PURPOSE: To investigate the effects of three commonly used general anesthetics on intraocular pressure (IOP) in mouse. METHODS: Fifteen 2-3-month-old C57BL/6J mice were randomly divided into three groups (each group, n=5). A non-invasive TonoLab tonometer (Icare LAB, Icare Finland Oy, Espoo, Finland) was used to measure IOP at 0, 5, 10, 15, 20, 30 min after mice were anesthetized, respectively, by intraperitoneal injection of sodium pentobarbital (150 mg/kg), chloral hydrate (500 mg/kg) and a mixture of ketamine and xylazine (75 mg/kg and 13.6 mg/kg). IOP were obtained in the daytime and nighttime. Anterior segment was photographed and palpebral fissure height was measured offline. RESULTS: Immediately after anesthesia, the averaged IOPs in the three groups were 17.2 +/- 1.5, 16.7 +/- 1.4 and 17.3 +/- 2.4 mmHg in the daytime and 19.3 +/- 2.1, 21.3 +/- 1.1 and 21.7 +/- 1.5 mmHg in the nighttime. Thereafter, the averaged IOPs in sodium pentobarbital and chloral hydrate groups showed a trend of decline. Then IOPs became stable at 10-15 min after anesthesia. In contrast, the IOPs of ketamine and xylazine injected group increased to 23.7-25.1 mmHg at 10-15 min in the daytime and 26.1 27.7 mmHg in the nighttime. Compared to chloral hydrate and sodium pentobarbital treated mice (2.4 +/- 0.1 mm, 1.7 +/- 0.0 mm), ketamine and xylazine injected animals had significantly increased palpebral fissure height (3.6 +/- 0.3 mm, p<0.01). CONCLUSION: General anesthetics have a large impact on mouse IOP. Sodium pentobarbital and chloral hydrate reduce but the ketamine and xylazine mixture increases mouse IOP. IOP levels become stabilized at 10 to 15 min after anesthesia. The ketamine and xylazine cocktail mediated elevation of palpebral fissure height may be associated with an increasing of intraorbital pressure. Measurement performs at 10-15 min after anesthesia may obtain more reliable IOPs. PMID- 24215505 TI - Time-resolved probes based on guanine/thymine-rich DNA-sensitized luminescence of terbium(III). AB - In this study, we have developed a novel strategy to highly sensitize the luminescence of terbium(III) (Tb(3+)) using a designed guanine/thymine-rich DNA (5'-[G3T]5-3') as an antenna ligand, in which [G3T]5 improved the luminescence of Tb(3+) by 3 orders of magnitude due to energy transfer from nucleic acids to Tb(3+) (i.e., antenna effect). Furthermore, label-free probes for the luminescent detection of biothiols, Ag(+), and sequence-specific DNA in an inexpensive, simple, and mix-and-read format are presented based on the [G3T]5-sensitized luminescence of Tb(3+) (GTSLT). The long luminescence lifetime of the probes readily enables time-resolved luminescence (TRL) experiments. Hg(2+) can efficiently quench the luminescence of Tb(3+) sensitized by [G3T]5 (Tb(3+)/[G3T]5); however, biothiols are readily applicable to selectively grab Hg(2+) for restoration of the luminescence of Tb(3+)/[G3T]5 initially quenched by Hg(2+), which can be used for "turn on" detection of biothiols. With the use of cytosine (C)-rich oligonucleotide c[G3T]5 complementary to [G3T]5, the formed [G3T]5/c[G3T]5 duplex cannot sensitize the luminescence of Tb(3+). However, in the presence of Ag(+), Ag(+) can combine the C base of c[G3T]5 to form C-Ag(+)-C complexes, leading to the split of the [G3T]5/c[G3T]5 duplex and then release of [G3T]5. The released [G3T]5 acts as an antenna ligand for sensitizing the luminescence of Tb(3+). Therefore, the Tb(3+)/[G3T]5/c[G3T]5 probe can be applied to detect Ag(+) in a "turn on" format. Moreover, recognition of target DNA via hybridization to a molecular beacon (MB)-like probe (MB-[G3T]5) can unfold the MB [G3T]5 to release the [G3T]5 for sensitizing the luminescence of Tb(3+), producing a detectable signal directly proportional to the amount of target DNA of interest. This allows the development of a fascinating label-free MB probe for DNA sensing based on the luminescence of Tb(3+). Results and methods reported here suggest that a guanine/thymine-rich DNA-sensitized luminescence probe of Tb(3+) represents a new opportunity for versatile background-free biosensing applications. PMID- 24215507 TI - Three new basidiomycetous yeasts, Pseudozyma alboarmeniaca sp. nov., Pseudozyma crassa sp. nov. and Pseudozyma siamensis sp. nov. isolated from Thai patients. AB - We previously reported the first isolation of Pseudozyma species from the blood of Thai patients. In this study, three additional new Pseudozyma species were isolated from clinical specimens from Thai patients. The Pseudozyma species showed relatively low sensitivity to azole antifungal agents. The names proposed for these isolates are Pseudozyma alboarmeniaca (DMST 17135(T) = JCM 12454(T ) = CBS 9961(T)), Pseudozyma crassa (DMST 17136(T ) = JCM 12455(T) = CBS 9959(T)) and Pseudozyma siamensis (DMST 17137(T ) = JCM 12456(T) CBS 9960(T)), where DMST is Department of Medical Sciences Culture Collection, JCM is Japan Collection of Microorganisms and CBS is Centraalbureau voor Schimmelcultures. PMID- 24215508 TI - Colombia's racial crucible: Y chromosome evidence from six admixed communities in the Department of Bolivar. AB - OBJECTIVES: To determine the African, European and Native-American paternal contributions in genetic samples from the Department of Bolivar (Colombia) with the aims of establishing (1) possible population substructures, and (2) the proportion of biological African heritage in admixed populations of European, Amerindian, and African descent. METHODS: Y-SNPs were typed in samples from six communities, including Palenque (renowned for its African linguistic and cultural heritage). RESULTS: Findings reveal a high diversity of Y-haplogroups. With the exception of Palenque, the sum of European male lineages uniformly exceeded 57%. In Palenque, African lineages accounted for 57.7% of its chromosomes, with European male lineages constituting a mere 38.5%. In Pinillos, a significant proportion (23.8%) of the chromosomes belongs to the Native American haplogroup Q1a3a*-M3. Genetic differentiation analyses reveal significant divergences in most pairwise comparisons among the Bolivar municipalities, and the same holds between Bolivar and other South American populations. CONCLUSIONS: Heterogeneous patterns of admixture reveal a genetic substructure within the Department of Bolivar. On the paternal side, five out of the six communities studied exhibit a predominantly European gene pool. The exception is Palenque, where European input (38%) is more significant than we had expected. PMID- 24215509 TI - Metal-free enantioselective hydroxyamination of aldehydes with nitrosocarbonyl compounds catalyzed by an axially chiral amine. AB - The first example of a highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from hydroxamic acid derivatives was realized by combined use of TEMPO and BPO as the oxidant in the presence of a binaphthyl-modified amine catalyst. PMID- 24215506 TI - Topical antimicrobials for burn infections - an update. AB - The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature's way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections. PMID- 24215510 TI - Effect of corchorusin-D, a saikosaponin like compound, on B16F10 melanoma cells (in vitro and in vivo). AB - Corchorusin-D (COR-D), isolated from Corchorus acutangulus, was reported to induce apoptosis in leukemic cells. However, no studies concerning its activity on melanoma cells have been reported. We have evaluated its in vitro anti-cancer activity on melanoma cells (B16F10, SK-MEL-28, and A375). The results demonstrate that COR-D showed maximum inhibition of B16F10 cells in vitro. COR-D induced mitochondrial dysfunction and altered the Bax/Bcl-2 ratio with down regulation of pro-caspases 9 and activation of caspase 3 in B16F10 cells, triggering intrinsic pathway of apoptosis. Moreover, it inhibited the in vivo B16F10 tumor growth and increased the survival rate of mice. Greater number of Annexin V-FITC and propidium iodide (PI)-positive tumor cells signified that COR-D induced apoptosis in vivo also. The reduction in tumor growth is well correlated with decreased microvascular density of the tumor cells in treated mice. In conclusion, this study reveals that COR-D-induced mitochondrial dysfunction is responsible for the induction of apoptotic cell death. PMID- 24215512 TI - Sub 60 mV/decade switch using an InAs nanowire-Si heterojunction and turn-on voltage shift with a pulsed doping technique. AB - We report changes of turn-on voltage in InAs-Si heterojunction steep subthreshold slope transistors by the Zn-pulsed doping technique for InAs nanowire channels. The doping of the nanowire channel moderately changes turn-on voltage from negative to positive voltage, while keeping a steep subthreshold-slope of 30 mV/decade under reverse bias direction. The formation of pseudointrinsic InAs segment is found to be important to make a normally off transistor with a steep subthreshold slope. PMID- 24215511 TI - Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. AB - BACKGROUND: The purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients. METHODS: Primary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided. RESULTS: FISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9% and 13.6% of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95% confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen. CONCLUSIONS: This study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients. PMID- 24215513 TI - Wine metabolomics: objective measures of sensory properties of semillon from GC MS profiles. AB - The contribution of volatile aroma compounds to the overall composition and sensory perception of wine is well recognized. The classical targeted measurement of volatile compounds in wine using GC-MS is laborious and only a limited number of compounds can be quantified at any time. Application of an automated multivariate curve resolution technique to nontargeted GC-MS analysis of wine makes it possible to detect several hundred compounds within a single analytical run. Hunter Valley Semillon (HVS) is recognized as a world class wine with a range of styles. Subtle characters reliant upon the development of bottle maturation characteristics are a feature of highly esteemed HVS. In this investigation a metabolomic approach to wine analysis, using multivariate curve resolution techniques applied to GC-MS profiles coupled with full descriptive sensory analysis, was used to determine the objective composition of various styles of HVS. Over 250 GC-MS peaks were extracted from the wine profiles. Sensory scores were analyzed using PARAFAC prior to development of predictive models of sensory features from the extracted GC-MS peak table using PLS regression. Good predictive models of the sensorial attributes honey, toast, orange marmalade, and sweetness, the defining traits for HVS, could be determined from the extracted peak tables. Compound identification for these rated attributes indicated the importance of a range of ethyl esters, aliphatic alcohols and acids, ketones, aldehydes, furanic derivatives, and norisoprenoids in the development of HVS and styles. The development of automated metabolomic data analysis of GC-MS profiles of wines will assist in the development of wine styles for specific consumer segments and enhance understanding of production processes on the ultimate sensory profiles of the product. PMID- 24215515 TI - Identifying core NANDA-I nursing diagnoses, NIC interventions, NOC outcomes, and NNN linkages for heart failure. AB - PURPOSE: The purpose of the study was to identify the core nursing diagnoses, interventions, outcomes, and linkages using standardized nursing terminologies for patients with heart failure (HF). METHODS: For this study a retrospective descriptive design was used. The frequently used NANDA-I, NIC, NOC, and NNN linkages were identified through 272 inpatient records of patients discharged with HF in a midwestern community. FINDINGS: The findings indicate that the top 10 NANDA-I, NIC, and NOC accounted for more than 50% of nursing diagnoses, interventions, and outcomes. The most frequently used top 10 NNN linkages were identified for patients with HF. CONCLUSION AND PRACTICE IMPLICATIONS: The identified core NANDA-I, NIC, NOC, and NNN linkages for HF from this study provide scope of practice of nurses working in HF clinics. PMID- 24215514 TI - Angiotensin type 1a receptor-deficient mice develop diabetes-induced cardiac dysfunction, which is prevented by renin-angiotensin system inhibitors. AB - BACKGROUND: Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several cell types, in response to high ambient glucose levels. In cardiac myocytes, intracellular angiotensin (ANG) II synthesis and actions are ACE and AT1 independent, respectively. However, a role of this system in diabetes induced organ damage is not clear. METHODS: To determine a role of the intracellular ANG II in diabetic cardiomyopathy, we induced diabetes using streptozotocin in AT1a receptor deficient (AT1a-KO) mice to exclude any effects of extracellular ANG II. Further, diabetic animals were treated with a renin inhibitor aliskiren, an ACE inhibitor benazeprilat, and an AT1 receptor blocker valsartan. RESULTS: AT1a-KO mice developed significant diastolic and systolic dysfunction following 10 wks of diabetes, as determined by echocardiography. All three drugs prevented the development of cardiac dysfunction in these animals, without affecting blood pressure or glucose levels. A significant down regulation of components of the kallikrein-kinin system (KKS) was observed in diabetic animals, which was largely prevented by benazeprilat and valsartan, while aliskiren normalized kininogen expression. CONCLUSIONS: These data indicated that the AT1a receptor, thus extracellular ANG II, are not required for the development of diabetic cardiomyopathy. The KKS might contribute to the beneficial effects of benazeprilat and valsartan in diabetic cardiomyopathy. A role of intracellular ANG II is suggested by the inhibitory effects of aliskiren, which needs confirmation in future studies. PMID- 24215516 TI - On the mechanism of phase transfer catalysis in Brust-schiffrin synthesis of metal nanoparticles. AB - The two-phase Brust-Schiffrin method (BSM) is used to synthesize highly stable nanoparticles of noble metals. A phase transfer catalyst (PTC) is used to bring in aqueous phase soluble precursors into the organic phase to enable particle synthesis there. Two different mechanisms for phase transfer are advanced in the literature. The first mechanism considers PTC to bring in an aqueous phase soluble precursor by complexing with it. The second mechanism considers the ionic species to be contained in inverse micelles of PTC, with a water core inside. A comprehensive experimental study involving measurement of interfacial tension, viscosity, water content by Karl-Fischer titration, static light scattering, (1)H NMR, and small-angle X-ray scattering is reported in this work to establish that the phase transfer catalyst tetraoctylammonium bromide transfers ions by complexing with them, instead of encapsulating them in inverse micelles. The findings have implications for particle synthesis in two-phase methods such as BSM and their modification to produce more monodispersed particles. PMID- 24215517 TI - Variation in the hindgut microbial communities of the Florida manatee, Trichechus manatus latirostris over winter in Crystal River, Florida. AB - The Florida manatee, Trichechus manatus latirostris, is a hindgut-fermenting herbivore. In winter, manatees migrate to warm water overwintering sites where they undergo dietary shifts and may suffer from cold-induced stress. Given these seasonally induced changes in diet, the present study aimed to examine variation in the hindgut bacterial communities of wild manatees overwintering at Crystal River, west Florida. Faeces were sampled from 36 manatees of known sex and body size in early winter when manatees were newly arrived and then in mid-winter and late winter when diet had probably changed and environmental stress may have increased. Concentrations of faecal cortisol metabolite, an indicator of a stress response, were measured by enzyme immunoassay. Using 454-pyrosequencing, 2027 bacterial operational taxonomic units were identified in manatee faeces following amplicon pyrosequencing of the 16S rRNA gene V3/V4 region. Classified sequences were assigned to eight previously described bacterial phyla; only 0.36% of sequences could not be classified to phylum level. Five core phyla were identified in all samples. The majority (96.8%) of sequences were classified as Firmicutes (77.3 +/- 11.1% of total sequences) or Bacteroidetes (19.5 +/- 10.6%). Alpha-diversity measures trended towards higher diversity of hindgut microbiota in manatees in mid-winter compared to early and late winter. Beta-diversity measures, analysed through PERMANOVA, also indicated significant differences in bacterial communities based on the season. PMID- 24215518 TI - Periocular photodynamic therapy for squamous intra-epidermal carcinoma. AB - OBJECTIVES: To evaluate the response of Metvix photodynamic therapy (PDT) for the treatment of periocular Bowen's disease. METHODS: Four patients with biopsy proven Bowen' disease were treated with Metvix PDT between November 2010 and January 2012. A detailed description of the technique used is described. RESULTS: All of the patients tolerated the PDT well. All had some clinical response to the treatment, although there was not complete, lasting resolution beyond one year in three out of the four cases. CONCLUSION: PDT can be a good treatment in its own right in selected cases of periocular Bowen's disease. PMID- 24215519 TI - Screening and determination of sibutramine in adulterated herbal slimming supplements by HPTLC-UV densitometry. AB - The adulteration of herbal supplements is of growing importance, especially when they contain undeclared compounds like sibutramine that are unsafe drugs. Sibutramine was withdrawn from US and European markets in 2010. In this study, an HPTLC-UV densitometric method was developed for the quantification of sibutramine in herbal diet foods. Sample extracts were directly applied onto HPTLC silica gel plates and separated with a mobile phase made of a toluene-methanol mixture. Sibutramine was quantified at 225 nm and its unequivocal identification was confirmed by MS using a TLC-MS interface. During two surveys, 52 weight loss supplements obtained via the Internet were screened. Half of those were adulterated with sibutramine at amounts reaching up to 35 mg per capsule. The results of this validated HPTLC method were compared with those obtained by HPLC UV and HPLC-MS/MS. The results were not significantly different with the three methods. PMID- 24215520 TI - Expression profile and regulation of spore and parasporal crystal formation associated genes in Bacillus thuringiensis. AB - Bacillus thuringiensis, a Gram-positive endospore-forming bacterium, is characterized by the formation of parasporal crystals consisting of insecticidal crystal proteins (ICPs) during sporulation. We reveal gene expression profiles and regulatory mechanisms associated with spore and parasporal crystal formation based on transcriptomics and proteomics data of B. thuringiensis strain CT-43. During sporulation, five ICP genes encoded by CT-43 were specifically transcribed; moreover, most of the spore structure-, assembly-, and maturation associated genes were specifically expressed or significantly up-regulated, with significant characteristics of temporal regulation. These findings suggest that it is essential for the cell to maintain efficient operation of transcriptional and translational machinery during sporulation. Our results indicate that the RNA polymerase complex delta and omega subunits, cold shock proteins, sigma factors, and transcriptional factors as well as the E2 subunit of the pyruvate dehydrogenase complex could cooperatively participate in transcriptional regulation via different mechanisms. In particular, differences in processing and modification of ribosomal proteins, rRNA, and tRNA combined with derepression of translational inhibition could boost the rate of ribosome recycling and assembly as well as translation initiation, elongation, and termination efficiency, thereby compensating for the reduction in ribosomal levels. The efficient operation of translational machineries and powerful protein-quality controlling systems would thus ensure biosyntheses of a large quantity of proteins with normal biological functions during sporulation. PMID- 24215522 TI - Refugia, colonization and diversification of an arid-adapted bird: coincident patterns between genetic data and ecological niche modelling. AB - Phylogeographical studies are common in boreal and temperate species from the Palaearctic, but scarce in arid-adapted species. We used nuclear and mitochondrial markers to investigate phylogeography and to estimate chronology of colonization events of the trumpeter finch Bucanetes githagineus, an arid-adapted bird. We used 271 samples from 16 populations, most of which were fresh samples but including some museum specimens. Microsatellite data showed no clear grouping according to the sampling locations. Microsatellite and mitochondrial data showed the clearest differentiation between Maghreb and Canary Islands and between Maghreb and Western Sahara. Mitochondrial data suggest differentiation between different Maghreb populations and among Maghreb and Near East populations, between Iberian Peninsula and Canary Islands, as well as between Western Sahara and Maghreb. Our coalescence analyses indicate that the trumpeter finch colonized North Africa during the humid Marine Isotope Stage 5 (MIS5) period of the Sahara region 125 000 years ago. We constructed an ecological niche model (ENM) to estimate the geographical distribution of climatically suitable habitats for the trumpeter finch. We tested whether changes in the species range in relation to glacial-interglacial cycles could be responsible for observed patterns of genetic diversity and structure. Modelling results matched with those from genetic data as the species' potential range increases in interglacial scenarios (in the present climatic scenario and during MIS5) and decreases in glacial climates (during the last glacial maximum, LGM, 21 000 years ago). Our results suggest that the trumpeter finch responded to Pleistocene climatic changes by expanding and contracting its range. PMID- 24215523 TI - Psychometric evaluation of the Danish version of Satisfaction with Daily Occupations (SDO). AB - AIMS: The Satisfaction with Daily Occupations (SDO) scale assesses satisfaction within the domains of work, leisure, domestic tasks, and self-care. The aim was to investigate the psychometric properties of the Danish version of the SDO when used with asylum seekers. METHODS: The participants were 93 Danes without known ill health and 43 asylum seekers. They completed the SDO and rated their perceived health, activity level, and general satisfaction with daily occupations. Translation into Danish and back-translation into Swedish was made by professional interpreters. RESULTS: Internal consistency was alpha = 0.75 for the Danish sample and alpha = 0.79 for the asylum seekers. The SDO distinguished between asylum seekers and the Danish sample, suggesting criterion validity. Concurrent validity, analysed against general satisfaction with daily occupations, was indicated for both samples. Discriminant validity was indicated against self-rated health for both samples and against activity level for the Danish sample. There was, however, a correlation of 0.65 between the SDO satisfaction score and activity level for the asylum seekers. CONCLUSION: The SDO exhibited satisfactory internal consistency and criterion and concurrent validity. The findings regarding discriminant validity were somewhat inconclusive. The Danish SDO may be regarded as psychometrically sound but further psychometric testing is needed. PMID- 24215524 TI - An "alternating instructions" version of the Autobiographical Memory Test for assessing autobiographical memory specificity in non-clinical populations. AB - There is limited research regarding how executive processes contribute to key cognitive deficits in depression, particularly impoverished retrieval of autobiographical memory. This study tested a novel version of the Autobiographical Memory Test (AMT), the "Alternating Instructions" AMT (AMT-AI), to determine how participants could flexibly retrieve specific and categoric autobiographical memories. The AMT-AI consisted of a standard AMT (AMT-S), a categoric version of the AMT (AMT-R), and a section of alternating instructions (AI) in which the rules required the participant to alternate between retrieval of categoric and specific memories. A total of 49 university students completed the AMT-AI, and self-report measures of depressive symptomatology and ruminative thinking. Results showed that the mean proportion of specific memories recalled on the AMT-AI was significantly lower than on the AMT-S. Also, reduced memory specificity on the AMT-AI, but not the AMT-S, was significantly negatively correlated with increased scores on measures of depressive symptomatology and ruminative thinking. Collectively the data suggested that the AMT-AI, relative to the traditional AMT, may be more sensitive to memory specificity in non-clinical populations. Future research is warranted to further determine the psychometric properties and utility of the AMT-AI. PMID- 24215525 TI - Systemic allergic dermatitis caused by thiamine after iontophoresis. PMID- 24215526 TI - Allergic contact dermatitis caused by menthoxypropanediol in a lip cosmetic. PMID- 24215527 TI - Allergic contact dermatitis caused by self-adhesive electrocardiography electrodes in an infant. PMID- 24215528 TI - Patch test reaction to p-phenylenediamine can persist for more than 1 month. PMID- 24215529 TI - Glyceryl (mono)caprylate - a new contact allergen. PMID- 24215530 TI - Henna stone: a lesser-known solid material from which to obtain black henna paste. PMID- 24215531 TI - Does cobalt spot testing of copper items result in false-positive test reactions? PMID- 24215532 TI - Eltrombopag for the treatment of thrombocytopenia in patients with malignant and non-malignant hematologic disorders. AB - INTRODUCTION: Eltrombopag (EP) is an orally bioavailable, non-peptide, thrombopoietin receptor (TPO-R) agonist developed to stimulate platelet production. EP is a small hydrazone molecule which interacts with the transmembrane domain of TPO-R and promotes megakaryopoiesis, and a subsequent increase in platelet number. To date, multiple large clinical trials have demonstrated the ability of EP to reduce the burden of thrombocytopenia and its associated side effects in patients with chronic immune thrombocytopenia purpura and patients with hepatitis-C related thrombocytopenia. Given these promising results and the morbidity associated with thrombocytopenia in cancer patients, there is significant interest in investigating the role of EP for thrombocytopenia secondary to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). AREAS COVERED: In this review, the authors address the potential utility of EP for patients with AML and MDS with thrombocytopenia. The review provides an overview of the rationale for the development of EP in AML and MDS, and the mechanism(s) of action of EP. The authors focus on preclinical data describing the effectiveness of EP as both a platelet-stimulating, and an anti leukemia agent and describe the use of EP in clinical trials. EXPERT OPINION: EP has the potential to be an effective supportive care agent, improving platelet counts and decreasing thrombocytopenia-related morbidity, in patients with AML and MDS. Large, randomized clinical trials are needed to assess the efficacy of EP in reducing the duration and severity of thrombocytopenia, as well assess the clinical utility of EP as an anti-leukemia agent. PMID- 24215533 TI - Patients' direction, empowerment and quality of life in haemodialysis. AB - The maintenance of an adequate of quality of life (QoL) represents a critical issue in the management of patients in haemodialysis and is also used to assess the effectiveness of health care programmes. The Consumer Direction Theory of Empowerment (CDTE) implies that greater patient direction in policy formulation and services delivery, together with an increased community integration, endorses a process which leads to a better QOL. The aim of the study was to test a contextualized version of CDTE in an ambulatory for patients in haemodialysis. Sixty-nine patients completed a questionnaire measuring the following variables: Patient direction, family integration, self-efficacy in managing the disease, mental and physical health. The results showed that patient direction and family integration have an indirect effect on QoL, through self-efficacy in managing the disease. The hypotheses were thus confirmed, providing support for the potential of CDTE in the context of health services for haemodialysis patients. Implications for the implementation of health programmes aimed at improving QoL of patients in haemodialysis are discussed, including interventions focused on psychological and contextual factors. PMID- 24215535 TI - Calpain protease causes hypoxia-induced proteolysis in cultured human retina. AB - PURPOSE/AIM: Calpain proteases are known to be involved in retinal cell death in animal models. The purpose of the present study was to test for calpain activation in human retinas cultured under hypoxic conditions. MATERIALS AND METHODS: Calpain activation was detected by immunoblotting for calpain substrates in human and monkey retinas cultured in gas generating pouches to reduce oxygen. RESULTS: Hypoxia caused activation of calpains as measured by accumulation of the calpain-specific 145 kDa alpha-spectrin breakdown product. Opsin-1 (photoreceptor marker) and vimentin (Muller cell marker) were degraded. Calpain inhibitor SNJ 1945 ameliorated these changes. Results were similar to comparative data from cultured monkey retinas. CONCLUSIONS: In cultured human retina, hypoxia caused activation of calpain and subsequent proteolysis of critical substrates. The efficacy of SNJ-1945 in ameliorating these changes indicated that it might be useful to test as a drug for protecting against pathologic proteolysis of photoreceptor and Muller cells. PMID- 24215534 TI - Oxygen reduction catalyzed by Au-TiO2 nanocomposites in alkaline media. AB - Au-TiO2 nanocomposites were prepared by chemical deposition of gold nanoparticles onto TiO2 nanocolloids that were synthesized by a hydrothermal method. Transmission electron microscopic measurements showed that the TiO2 colloids exhibited an average diameter of about 5 nm and clearly defined lattice fringes that were consistent with those of anatase TiO2 and formed rather large agglomerates that spanned a few hundred nanometers in length. Additionally, gold nanoparticles were found to be embedded within the TiO2 matrices, and the size increased with increasing gold loading but all ranged from 10 to 50 nm in diameter. Consistent results were obtained in X-ray diffraction measurements. Electrochemical studies demonstrated that the resulting Au-TiO2 nanocomposites exhibited apparent electrocatalytic activity in oxygen reduction that was markedly improved as compared to that of TiO2 particles alone, as reflected in the onset potential, number of electron transfers involved, and kinetic current density. Among the series, the best catalyst for oxygen reduction was identified with the Au/Ti atomic ratio of 5.2%. The enhanced oxygen reduction kinetics was ascribed to the dissociation of water and formation of surface-adsorbed hydroxyl moieties that was facilitated by the loading of gold nanoparticles onto the TiO2 colloids. PMID- 24215536 TI - Sensitive electrochemiluminescence biosensor based on Au-ITO hybrid bipolar electrode amplification system for cell surface protein detection. AB - Here we developed a novel hybrid bipolar electrode (BPE)-electrochemiluminescence (ECL) biosensor based on hybrid bipolar electrode (BPE) for the measurement of cancer cell surface protein using ferrocence (Fc) labeled aptamer as signal recognition and amplification probe. According to the electric neutrality of BPE, the cathode of U-shaped ITO BPE was electrochemically deposited by Au nanoparticles (NPs) to enhance its conductivity and surface area, decrease the overpotential of O2 reduction, which would correspondingly increase the oxidation current of Ru(bpy)3(2+)/tripropylamine (TPA) on the anode of BPE and resulting a ~4-fold enhancement of ECL intensity. Then a signal amplification strategy was designed by introducing Fc modified aptamer on the anode surface of BPE through hybridization for detecting the amount of mucin-1 on MCF-7 cells. The presence of Fc could not only inhibit the oxidation of Ru(bpy)3(2+) because of its lower oxidation potential, its oxidation product Fc(+) could also quench the ECL of Ru(bpy)3(2+)/TPA by efficient energy-transfer from the excited-state Ru(bpy)3(2+)* to Fc(+), making the ECL intensity greatly quenched. On the basis of the cathodic Au NPs induced ECL enhancing coupled with anodic Fc induced signal quenching amplification, the approach allowed detection of mucin-1 aptamer at a concentration down to 0.5 fM and was capable of detecting a minimum of 20 MCF-7 cells. Besides, the amount of mucin-1 on MCF-7 cells was calculated to be 9041 +/- 388 molecules/cell. This approach therefore shows great promise in bioanalysis. PMID- 24215537 TI - The impact of smoking status on 9.3 years incidence of cardiovascular and all cause mortality among Iranian men. AB - AIM: To examine the association of different smoking groups with cardiovascular disease (CVD), coronary heart diseases (CHD) and CVD attributed death and death due to all causes in a male Tehranian population. METHODS: From a population based study 3059 male individuals, aged >=30 years, free of CVD at baseline were evaluated for a median of 9.3 years. The adjusted hazard ratios (HRs) for incident CVD/CHD, total and CVD mortality regarding their smoking status were calculated using Cox proportional regression analysis, considering never smoking as reference. RESULTS: A total of 158 deaths, in which 78 were CVD attributable, occurred. Considering CVD and CHD events, this study identified 299 and 257 events, respectively. Being a past smoker significantly increased the risk of CVD events (HR = 2.42, CI = 1.28-0.56), however, it has no effect on CHD events, total and CVD mortality. Being a current smoker (more than 10 cigarettes a day) dramatically increased the risk of CVD/CHD events and total/CVD mortality. However, smoking less than 10 cigarettes per day only increased the risk of CVD (HR = 2.12, CI = 1.14-3.95) and its mortality (HR = 4.57, CI = 1.32-15.79). CONCLUSION: The findings indicate that smoking increases the risk of incident CVD/CHD, total and CVD mortality, particularly CVD mortality. These outcomes were attributable to the daily amount of cigarettes smoked. Past smokers still had higher risk for CVD events, which cessation may not reduce. PMID- 24215538 TI - Impact of roadside tree lines on indoor concentrations of traffic-derived particulate matter. AB - Exposure to airborne particulate pollution is associated with premature mortality and a range of inflammatory illnesses, linked to toxic components within the particulate matter (PM) assemblage. The effectiveness of trees in reducing urban PM10 concentrations is intensely debated. Modeling studies indicate PM10 reductions from as low as 1% to as high as ~60%. Empirical data, especially at the local scale, are rare. Here, we use conventional PM10 monitoring along with novel, inexpensive magnetic measurements of television screen swabs to measure changes in PM10 concentrations inside a row of roadside houses, after temporarily installing a curbside line of young birch trees. Independently, the two approaches identify >50% reductions in measured PM levels inside those houses screened by the temporary tree line. Electron microscopy analyses show that leaf captured PM is concentrated in agglomerations around leaf hairs and within the leaf microtopography. Iron-rich, ultrafine, spherical particles, probably combustion-derived, are abundant, form a particular hazard to health, and likely contribute much of the measured magnetic remanences. Leaf magnetic measurements show that PM capture occurs on both the road-proximal and -distal sides of the trees. The efficacy of roadside trees for mitigation of PM health hazard might be seriously underestimated in some current atmospheric models. PMID- 24215539 TI - Iron-catalyzed ortho-allylation of aromatic carboxamides with allyl ethers. AB - Arenes possessing an N-(quinolin-8-yl)amide directing group are ortho-allylated with allyl phenyl ether in the presence of an iron/diphosphine catalyst and an organometallic base at 50-70 degrees C. The reaction proceeds via fast iron catalyzed C-H activation, followed by reaction of the resulting iron intermediate with the allyl ether in gamma-selective fashion. PMID- 24215540 TI - The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation. AB - The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting. PMID- 24215541 TI - Synthesis and cytotoxicity of novel 20-O-linked homocamptothecin ester derivatives as potent topoisomerase I inhibitors. AB - In an attempt to improve the antitumor activity of homocamptothecins (hCPTs), a series of novel 20-O-linked hCPT ester derivatives were first designed and synthesized based on a synthetic route, by which hCPTs are acylated with different substituted phenoxyacetic acid ester derivatives. Most of the derivatives were assayed for in vitro cytotoxicity against six human cancer cell lines KB, KB/VCR, A549, HCT-8, Bel7402, and A2780, and most of the assayed compounds exhibited good antiproliferative activity on these tumor cell lines especially on KB. PMID- 24215542 TI - Synthesis of rhodium concave tetrahedrons by collectively manipulating the reduction kinetics, facet-selective capping, and surface diffusion. AB - This paper describes a facile synthesis of Rh tetrahedrons with concave side faces by collectively manipulating the reaction kinetics, facet-selective capping, and surface diffusion of atoms. Specifically, a combination of Na3RhCl6, triethylene glycol, l-ascorbic acid, and citric acid provides the right conditions for generating the concave tetrahedrons. After the formation of small Rh tetrahedral seeds through self-nucleation, the subsequently generated Rh atoms were selectively deposited onto the corner sites to generate Rh tetrapods. At the same time, the deposited atoms could diffuse from the corners to edges to generate concave side faces because the diffusion to face sites was restrained by the citric acid adsorbed on the {111} facets. This study offers deep insight into the growth mechanism involved the formation of noble-metal nanocrystals with concave surfaces. The Rh concave tetrahedrons were encased by a mix of {111} and {110} facets, showing great potential for catalytic applications. PMID- 24215543 TI - Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease. AB - BACKGROUND: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease. CASE PRESENTATION: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit. CONCLUSIONS: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. PMID- 24215545 TI - Liquid chromatography-mass spectrometry method for the quantitative determination of residues of selected veterinary hormones in powdered ingredients derived from bovine milk. AB - A rugged, quantitative liquid chromatography-tandem mass spectrometry method with modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) sample preparation for 17 selected veterinary hormones in six different powdered ingredients derived from bovine milk was developed and comprehensively validated. A universal post-extraction spiked matrix-matching approach based on whole milk powder has been successfully implemented. Three validation runs based on four levels of pre-extraction spiked quality control (QC) samples have been conducted. Overall accuracy (86-117%), overall precision (<20% RSD), selectivity, absolute extraction recovery (62-82%), matrix effect (<15% for most compounds), limits of detection (0.1-0.8 MUg/kg, except for diethylstilbestrol at 3.8 MUg/kg), limits of quantitation (0.2-2.0 MUg/kg, except for diethylstilbestrol at 10.0 MUg/kg), and extract stability (48 h) have been determined. The method is proposed for the routine analysis of hormones potentially present in powdered ingredients derived from bovine milk. PMID- 24215546 TI - Synthesis of 2-methoxy benzoquinone and 2,6-dimethoxybenzoquinone by selected lactic acid bacteria during sourdough fermentation of wheat germ. AB - BACKGROUND: In the last decade, several studies described the promising cytotoxic activity of fermented wheat germ towards cancer cell lines and during in vivo clinical trials. Recent data suggested that the antiproliferative, antimetastatic and immunological effects of this preparation are mainly attributed to quinones. This study aimed at exploiting the potential of sourdough lactic acid bacteria fermentation to release 2-methoxy benzoquinone, and 2,6-dimethoxybenzoquinone, which are naturally present in wheat germ as glycosylated and non-physiologically active form. RESULTS: Preliminarily, forty strains of lactic acid bacteria, previously isolated from wheat germ, were in vitro screened based on beta glucosidase activity. Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5 were selected based on the highest enzyme activity and on technology features. These strains were used in combination to ferment wheat germ. Raw wheat germ, without bacterial inoculum, was subjected to the same incubation and used as the control. The sourdough fermented wheat germ was characterized based on microbiological, physico-chemical and biochemical features. During incubation, the release of the non-glycosylated and physiologically active 2-methoxy benzoquinone, and 2,6-dimethoxybenzoquinone was almost completed during 24 h. Compared to the control, the concentration of the above bioactive compounds increased almost 4 and 6-folds. Both raw wheat germ (control) and sourdough fermented wheat germ were ex vivo assayed for the anti-proliferative activity towards various cell lines of germ cell tumor, colon carcinoma and ovarian carcinoma. While no effect was found for the raw wheat germ, the sourdough fermented preparation markedly and variously affected the human tumor cell lines. The values of IC50 ranged from 0.105 +/- 0.005 to 0.556 +/- 0.071 mg/ml, with a median value of IC50 of 0.302 mg/ml. CONCLUSIONS: These results are comparable to those found for other well-known pharmaceutical preparations, and may disclose the use of the sourdough fermented wheat germ as an ingredient, nutritional supplement and/or anticancer drug. PMID- 24215547 TI - Does documentation in nursing records of nutritional screening on admission to hospital reflect the use of evidence-based practice guidelines for malnutrition? AB - PURPOSE: To describe the documentation of nutrition-related data and wards referral to dieticians in a Belgian university hospital. METHOD: Retrospective analysis of 506 nursing records. FINDINGS: Body weight and height are documented in 22%. "Feeding assistance" and "usual food intake pattern" are documented in 68% of all cases, and in 71% it is marked whether the patient is on a diet. Eight percent of the patients are referred to a dietician, but the indications for these referrals are not clear. CONCLUSION: Given the poor documentation, most likely these patients are not adequately screened for malnutrition as recommended. IMPLICATIONS FOR NURSING PRACTICE: Nurses' documentation of nutrition-related data should be improved to facilitate treatment of malnutrition with tailored multidisciplinary interventions. PMID- 24215548 TI - Dispersions of attractive semiflexible fiberlike colloidal particles from bacterial cellulose microfibrils. AB - We prepared dispersions from bacterial cellulose microfibrils (CMF) of a commercial Nata de Coco source. We used an ultra-high-energy mechanical deagglomeration process that is able to disperse the CMFs from the pellicle in which they are organized in an irregular network. Because of the strong attractions between the CMFs, the dispersion remained highly heterogeneous, consisting of fiber bundles, flocs, and voids spanning tens to hundreds of micrometers depending on concentration. The size of these flocs increased with CMF concentration, the size of the bundles stayed constant, and the size of the voids decreased. The observed percolation threshold in MFC dispersions is lower than the theoretical prediction, which is accounted for by the attractive interactions in the system. Because bacterial cellulose is chemically very pure, it can be used to study the interaction of attractive and highly shape anisotropic, semiflexible fiberlike colloidal particles. PMID- 24215544 TI - PPAR agonists as therapeutics for CNS trauma and neurological diseases. AB - Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID- 24215549 TI - Dental erosion due to GERD in patients with developmental disabilities: case theory. AB - Gastroesophageal reflux disease (GERD) is a common finding among individuals in our society. Unfortunately, the condition is even more prevalent in individuals with developmental disabilities. There are significant comorbidities that can affect the upper gastrointestinal tract. Erosion of tooth surfaces may be the first comorbidity that is detected in individuals unable to express physical discomfort associated with GERD. The dentist should be aware of these findings and able to refer the patient for medical management. In addition, an awareness of preventive regimens and restorative options is essential in maintaining a healthy dentition for these individuals. PMID- 24215550 TI - Economic outcomes of sequences which include monoclonal antibodies against vascular endothelial growth factor and/or epidermal growth factor receptor for the treatment of unresectable metastatic colorectal cancer. AB - BACKGROUND: Patients with unresectable, metastatic colorectal cancer with wild type Kirsten ras mutational status are eligible for sequential treatments which include monoclonal antibodies as first line (1L), second line (2L), or third line (3L) regimens. OBJECTIVE: To compare the economic outcomes of different sequences which include monoclonal antibodies for the treatment of unresectable metastatic colorectal cancer. METHODS: Individual drug regimens for 1L, 2L, and 3L treatments were compiled according to the clinical studies in the Summary of Product Characteristics for monoclonal antibodies. They were combined into plausible treatment sequences. Health outcomes were approximated using additive median PFS benefit, and economic outcomes were calculated with a treatment sequencing costing tool. Limitations of the analysis include the clinical trial data sources, cost assumptions, and the additive PFS approach. RESULTS: Seventeen sequences were evaluated. Results of the analysis show that sequences including 1L anti-EGFRs generally have relatively low-to-medium health outcomes at the highest comparative sequence costs compared to sequences including 2L anti-EGFRs, which have lower health outcomes at the lowest cost. Sequences including 3L anti EGFRs (sequential bevazicumab-based 1L and 2L) have the highest health outcomes, with potential cost savings of ?5972-?11,676 if replacing 2L anti-EGFRs or an additional cost of ?5909-?12,708 if replacing 1L anti-EGFR regimens. CONCLUSION: Clinical sequences consisting of 1L and 2L line bevacizumab followed by 3L anti EGFR potentially yield the greatest health outcomes associated with a reasonable trade-off in additional cost when replacing 1L anti-EGFRs and are potentially cost-saving if replacing 2L anti-EGFRs, per patient per lifetime. To maximize health outcomes, optimal sequences include anti-EGFRs as 3L regimen, with an approximately equivalent trade-off in costs between the most costly (anti-EGFR 2L) and least costly (anti-EGFR 1L) sequences. PMID- 24215551 TI - Analytical screening studies on irradiated food packaging. AB - Foods may be irradiated in their final packaging and this process may affect the composition of the packaging and in turn affect the migration of substances into food. Headspace and liquid injection GC-MS and HPLC with time-of-flight MS have been used to identify and estimate levels of radiolytic products in irradiated finished plastic packaging materials. Fifteen retail packaging materials were studied. Investigations were carried out into the effect of different irradiation types (gamma and electron beam), irradiation doses (1, 3, 7 and 10 kGy) and dose rates (5 kGy s(-1) for electron beam and 0.4 and 1.85 kGy h(-1) for gamma) on the radiolytic products. Any differences seen in comparing the two ionising radiation types were attributed largely to the very different dose rates; for electron beam a 10 kGy dose was delivered in just 2 s whereas using gamma it took 5.4 h. Differences were also seen when comparing the same samples irradiated at different doses. Some substances were not affected by irradiation, others decreased in concentration and others were formed upon increasing doses of irradiation. These results confirm that irradiation-induced changes do occur in substances with the potential to migrate and that the safety of the finished packaging material following irradiation should be assessed. PMID- 24215553 TI - Maternal sexual interactions affect offspring survival and ageing. AB - In many species, females exposed to increased sexual activity experience reductions in longevity. Here, in Drosophila melanogaster, we report an additional effect on females brought about by sexual interactions, an effect that spans generations. We subjected females to a sexual treatment consisting of different levels of sexual activity and then investigated patterns of mortality in their offspring. We found reduced probabilities of survival, increases in the rate of senescence and a pattern of reduced mean longevities, for offspring produced by mothers that experienced higher levels of sexual interaction. We contend that these effects constitute trans-generational costs of sexual conflict -the existence or implications of which have rarely been considered previously. Our results indicate that ongoing exposure by mothers to male precopulatory interactions is itself sufficient to drive trans-generational effects on offspring mortality. Thus, we show that increases in maternal sexual activity can produce trans-generational effects that permeate through to latter life stages in the offspring. This helps to elucidate the complex interplay between sex and ageing and provides new insights into the dynamics of adaptation under sexual selection. PMID- 24215554 TI - Effects of a soft prefabricated thumb orthosis in carpometacarpal osteoarthritis. AB - AIMS: To explore the feasibility and assess the effect of a prefabricated soft thumb-base orthosis on pain, hand strength, and activity performance in persons with osteoarthritis of the CMC joint. METHODS: In this randomized controlled trial, 29 patients received hand exercises only (control group) and 30 patients received hand exercises and an orthosis (orthosis group). The primary outcome was pain, while secondary outcomes included grip and pinch strength, and self reported symptoms and activity performance. Outcome assessments, and measures of grip strength and pain with and without orthosis in the orthosis group, were made after two months. RESULTS: 55 participants (mean age 70.5 years) completed all assessments. There were no significant differences between the groups in primary or secondary outcomes after two months. However, in the orthosis group, pain was significantly less when wearing the orthosis than when not wearing it. Participants reported that the orthosis felt uncomfortable during activities involving water and one-third wanted more support of the CMC joint. CONCLUSIONS: A soft prefabricated orthosis seems to have an immediate pain-relieving effect during use, but no effects in terms of less hand pain, or improved strength or activity performance when not worn. PMID- 24215555 TI - Mechanisms and potential therapeutic targets in allergic inflammation: recent insights. AB - Deeper insight into pathogenetic pathways and into the biological effects of immunomodulatory agents will help to optimize or adopt therapeutic strategies for atopic disorders. In this article, we highlight selected findings of potential therapeutic relevance that emerged from recent mechanistic studies with focus on molecular and cellular aspects of allergic inflammation. Furthermore, the often complex mechanisms of action of pleiotropic immunomodulatory agents, such as glucocorticoids, vitamin D, or intravenous immunoglobulin (IVIG), are discussed, as their dissection might reveal targets for novel therapeutics or lead to a more rational use of these compounds. Besides reporting novel evidence, this article points to areas of current debate or uncertainty and aims at stimulating scientific discussion and experimental work. PMID- 24215556 TI - Review of laquinimod and its therapeutic potential in multiple sclerosis. AB - INTRODUCTION: Multiple sclerosis (MS) is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Although major progress has occurred, MS is still an incurable disease. Further, parenteral application and/or safety issues of the currently licensed drugs are associated with low patient compliance. Thus, there remains an unmet need for the development of more effective and well-tolerated oral therapies for the treatment of MS. At this point in time, different oral available substances are under investigation and hold promise in the treatment of relapsing-remitting MS (RRMS). AREAS COVERED: The physical, chemical and pharmacological properties of laquinimod , as well as its suggested mechanisms of action, clinical efficacy and side-effect profile are reviewed. EXPERT OPINION: Laquinimod is a new orally administered synthetic drug designed as an immunomodulator. Its mechanisms of action are not yet fully elucidated. Studies in mice and humans revealed different mechanisms of action, including anti inflammatory and neuroprotective effects. So far, Phase II and Phase III clinical trials have shown its efficacy on magnetic resonance imaging based measures of disease activity, annualized relapse rate and disability progression in RRMS patients. Current data suggest a relatively modest efficacy by measures of relapse rate and there seems to be no superiority in comparison to established disease-modifying agents in relapsing-remitting MS. Further studies are necessary to evaluate both neuroprotective efficacy and optimal dosage of laquinimod in more detail. PMID- 24215557 TI - Inflammatory bowel diseases and psychological issues: A new approach for a systematic analysis of the academic debate. AB - Inflammatory bowel disease (IBD) has received increasing attention in recent years within the literature, due to its incidence and prevalence. The pathogenesis of IBD is still unclear, but the research community is increasingly suggesting that psychological issues may play a role in its aetiology and in exacerbation of symptoms. However, the literature regarding the psychological factors associated with IBD remains controversial and fragmented. The aim of the present study is twofold: (1) to identify, through a bibliometric analysis, the current state of the ongoing scientific debate regarding the relationship between IBD and psychological/psychiatric factors; (2) to analyse, through a qualitative software-based thematic analysis, the main themes characterizing the literature on this topic from 1988 to 2012. This study highlighted increasing number of academic publications in recent years regarding the multiplicity of factors related to the disease process in IBD, thus confirming the growing interest in this issue. IBD is becoming increasingly recognized by the medical literature as being exacerbated by a multi-componential process that needs to be studied through a biopsychosocial theoretical perspective which ables to orient multidisciplinary healthcare organizations and clinical interventions aimed at addressing IBD patient needs at different levels. This study also sheds light on two possible theoretical perspectives through which the academic community has considered IBD: A biomedical point of view that addresses the need for an etiological explanation of IBD and a behavioural point of view that aims at describing the observable symptoms and measurable health outcomes of clinical interventions such as patient adherence and engagement in the care and treatment process. PMID- 24215558 TI - Effects of the cycloplegic, cyclopentolate, on measurements of refraction in eyes of a strain of wild-type juvenile guinea pig (Cavia porcellus): a comparative study. AB - OBJECTIVE: To investigate the effect(s) of the cycloplegic, cyclopentolate, on measurements of refraction in eyes of a strain of wild-type guinea pig. METHODS: Both eyes of 13 wild-type juvenile guinea pigs (n=26 eyes) were examined both pre and post-mydriasis, using streak retinoscopy (SR) and eccentric infrared photoretinoscopy (EIP). On the day of measurement, three SR measurements were taken for each eye at 0900, 1000, 1100, 1400, 1500 and 1600, and three EIP measurements for each eye at 0930, 1030, 1130, 1430, 1530 and 1630. Cyclopentolate hydrochloride (1%) was topically administered three times to each eye at 5-min intervals: 1300, 1305 and 1310. RESULTS: Repeated measurements made by either method revealed that mydriasis did not significantly affect refractive stability (repeated measures, p>0.05). Depending on the stage of mydriasis, however, there were significant differences in measured refractive changes both SR and EIP (0.27 +/- 0.65 D, tSR=-2.095, PSR=0.04 and 0.73 +/- 1.06 D, tEIP= 3.494, PEIP=0.002, respectively) measurements. CONCLUSIONS: Cyclopentolate had only limited effects on measurements of refraction, indicating that direct SR or EIP measurements of refraction in this wild-type strain of juvenile guinea pig, without the use of a cycloplegic, yield reliable and stable results. PMID- 24215559 TI - 3D cross-linked nanoweb architecture of binder-free TiO(2) electrodes for lithium ion batteries. AB - The nanoweb structure of TiO2 anode, cross-linked between electrospun nanofibers, is directly fabricated on the current collector by utilizing the fluidity of low glass transition temperature polymer, poly(vinyl acetate), at room temperature. This characteristic enables us to fabricate the nanoweb structure by direct electrospinning on the current collector, followed by uniaxial pressing. This proposed structure facilitates electron transport through the direct conducting pathways between TiO2 active materials and current collector as well as provides strong adhesion strength to the current collector without polymeric binders. Consequently, we could achieve stable cycle performance up to 100 cycles and the excellent rate capability of ~60% at high rate charge/discharge condition of 10 C. PMID- 24215560 TI - Portable thermo-powered high-throughput visual electrochemiluminescence sensor. AB - This paper describes a portable thermo-powered high-throughput visual electrochemiluminescence (ECL) sensor for the first time. This sensor is composed of a tiny power supply device based on thermal-electrical conversion and a facile prepared array electrode. The ECL detection could be conducted with thermo-power, which is easily accessible. For example, hot water, a bonfire, or a lighted candle enables the detection to be conducted. And the assay can be directly monitored by the naked eye semiquantitatively or smart phones quantitatively. Combined with transparent electrode and array microreactors, a portable high throughput sensor was achieved. The portable device, avoiding the use of an electrochemical workstation to generate potential and a photomultiplier tube to receive the signal, is not only a valuable addition for traditional methods but also a suitable device for field operation or point-of-care testing. PMID- 24215561 TI - Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: development of an asymmetric aza-pinacol cyclization. AB - The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Bronsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2 amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis. PMID- 24215562 TI - Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH. AB - Lipid composition is expected to play an important role in modulating membrane enzyme activity, in particular if the substrates are themselves lipid molecules. A paradigmatic case is FAAH (fatty acid amide hydrolase), an enzyme critical in terminating endocannabinoid signalling and an important therapeutic target. In the present study, using a combined experimental and computational approach, we show that membrane lipids modulate the structure, subcellular localization and activity of FAAH. We report that the FAAH dimer is stabilized by the lipid bilayer and shows a higher membrane-binding affinity and enzymatic activity within membranes containing both cholesterol and the natural FAAH substrate AEA (anandamide). Additionally, co-localization of cholesterol, AEA and FAAH in mouse neuroblastoma cells suggests a mechanism through which cholesterol increases the substrate accessibility of FAAH. PMID- 24215563 TI - Genetic analysis of 15 STR loci from a Xibe population in Liaoning, Northeast of China. AB - BACKGROUND: In view of their high level of variability, autosomal short tandem repeats (STRs) are very useful as markers in the disciplines of forensic and population genetics studies. AIM: To investigate the diversity distributions of allelic frequencies of 15 loci from a sample from the Chinese Xibe ethnic group in Liaoning. SUBJECTS AND METHODS: Fifteen STR loci for 150 unrelated Xibe individuals from Liaoning, China were amplified simultaneously in a fluorescence based reaction using a 2720 Thermal cycler (ABI). Separation and detection of the amplified product were conducted with the Li-COR 4300 DNA Analyzer. RESULTS: In total, 117 alleles were observed, with the corresponding allele frequencies ranging from 0.001 to 0.507. D18S51 had the highest polymorphism (PIC = 0.840) among all 15 STR loci, whereas TPOX had the lowest (PIC = 0.590). The power of discrimination ranged from 0.801 for TH01 locus to 0.957 for D18S51 locus, whereas the power of exclusion ranged from a minimum 0.316 for TPOX locus to a maximum 0.720 for D21S11 locus. The phylogenetic tree established among worldwide populations showed that the Xibe population is far from other populations. CONCLUSION: Databases for the 15 STR loci will be useful for personal identification and paternity tests in the Xibe population and for the establishment of phylogenetic relationships between populations. PMID- 24215564 TI - An investigation of cognitive test performance across conditions of silence, background noise and music as a function of neuroticism. AB - The present study investigates the role of trait neuroticism on cognitive performance under distraction. Seventy participants were given a personality test and then undertook a number of different cognitive tasks in silence, in the presence of popular music and in background noise. It was predicted that performance on a general intelligence test, a test of abstract reasoning, and a mental arithmetic task would be adversely affected by background sounds. It was predicted that neuroticism would be negatively correlated with performance on the mental arithmetic task but only when the individuals were working in the presence of background sound. Stable vs. unstable participant's performance on a mental arithmetic task during noise was significantly higher as predicted. The results provided partial support for the hypotheses and are discussed with respect to previous findings in the literature on personality (particularly introversion extraversion) and distraction on cognitive task performance. Limitations are noted. PMID- 24215565 TI - Artemisinin-naphthoquine combination versus chloroquine-primaquine to treat vivax malaria: an open-label randomized and non-inferiority trial in Yunnan Province, China. AB - BACKGROUND: Plasmodium vivax is the main malaria parasite in China, and China is now making efforts to eliminate malaria by 2020. Radical cure of vivax malaria is one of challenges for malaria elimination. The purpose is to evaluate the efficacy and safety of artemisinin-naphthoquine (ANQ) versus chloroquine primaquine (CQ-PQ) in treatment of vivax malaria in Yunnan Province, China. METHODS: An open-label randomized and non-inferiority design, eligible patients with monoinfections of P. vivax were randomly assigned to receive either a total target dose of ANQ 24.5 mg/kg (naphthoquine 7 mg/kg and artemisinin 17.5 mg/kg), once a day for three days, or a total CQ dose of 24 mg base/kg, once a day for three days plus a PQ dose of 0.45 mg base/kg/day, once a day for eight days. Patients were followed up for one year. The difference in efficacy between ANQ and CQ-PQ was compared via Wilson's test. RESULTS: By day 42, the number of patients free of recurrence was 125 (98.4%; 95% Confidence interval, 94.4-99.8%) for ANQ arm and 123 (96.1%; 95%CI, 91.1-98.7%) for CQ-PQ, and non-significant (P = 0.4496). By day 365, the number was 101 (79.5%; 95%CI, 71.8-85.9%) for ANQ and 106 (82.8%; 95%CI, 75.1-88.9%) for CQ-PQ, and non-significant (P = 0.610). So the proportions of patients free of recurrence had no significant difference between ANQ and CQ-PQ groups by day 28, 42 and 365; compared with CQ-PQ, the side effect of ANQ was mild. CONCLUSION: ANQ is non-inferior to CQ-PQ in terms of patients free of recurrence, and safer than CQ-PQ. PMID- 24215566 TI - Factors related to cognitive function among elementary school children. AB - OBJECTIVE: The purpose of this study was to investigate cognitive functioning among elementary school children in Jordan. METHODS: A total of 468 children aged 6-12 years were recruited to participate in this study. Cognitive functioning was assessed using the LOTCA battery (Loewenstein Occupational Therapy Cognitive Assessment; Itzkovich et al., 2000). Information obtained from the parents included demographics, work and income data and child's daily behavior and school achievement. RESULTS: The results of this study showed that the cognitive functioning increased by 3.8 points for each increase in the child's GPA and increased by 2.35 points when the child ate breakfast regularly. By contrast, living in rural areas and smoking by a parent decreased cognitive functioning. CONCLUSIONS: Understanding of the child's cognitive abilities is critical to establishing intervention goals and to planning therapeutic activities. Screening of cognitive abilities and associated factors is essential for a comprehensive and accurate understanding of the child's abilities and limitations. Further research is recommended to investigate other factors in different populations. PMID- 24215567 TI - Tunable photoluminescence of monolayer MoS2 via chemical doping. AB - We demonstrate the tunability of the photoluminescence (PL) properties of monolayer (1L)-MoS2 via chemical doping. The PL intensity of 1L-MoS2 was drastically enhanced by the adsorption of p-type dopants with high electron affinity but reduced by the adsorption of n-type dopants. This PL modulation results from switching between exciton PL and trion PL depending on carrier density in 1L-MoS2. Achievement of the extraction and injection of carriers in 1L MoS2 by this solution-based chemical doping method enables convenient control of optical and electrical properties of atomically thin MoS2. PMID- 24215568 TI - Synthesis of a thiol-beta-cyclodextrin, a potential agent for controlling enzymatic browning in fruits and vegetables. AB - A thiol-beta-cyclodextrin was synthesized by a simple and environmentally friendly three-step method comprising epoxy activation of beta-cyclodextrin, thiosulfate-mediated oxirane opening, and further reduction of the S-alkyl thiosulfate to a thiol group. The final step was optimized by using thiopropyl agarose, a solid phase reducing agent with many advantages over soluble ones. beta-Cyclodextrin thiolation was confirmed by titration with a thiol-reactive reagent, NMR studies, and MALDI-TOF/TOF. Thiolated cyclodextrin had an average value of one thiol group per molecule. Thiol-beta-cyclodextrin proved to be an excellent agent for controlling polyphenol oxidase activity. This copper containing enzyme is responsible for browning in fruits and vegetables. Under the same conditions, thiol-beta-cyclodextrin generated a reductive microenvironment that increased the antibrowning effect on Red Delicious apples compared to unmodified beta-cyclodextrin. PMID- 24215569 TI - Troponin assays in the assessment of the equine myocardium. AB - In 2000, troponin assays were adopted as the test of choice for detection of myocardial injury in man. This decision was made after extensive testing and followed a 60 year search for a biomarker of myocardial damage with sufficient analytical sensitivity and specificity. This has led to proliferation of assays for use in human medicine, each requiring extensive testing and validation before it could be made available on the open market for human use. The search for ever more analytically sensitive assays and for a standard reference material continues. The adoption of troponin testing in veterinary medicine followed shortly after its development for use in man, providing a much-needed means of detecting and monitoring myocardial damage in horses. However, application of these tests in veterinary medicine has exclusively involved use of assays designed for and clinically validated in human patients. There is no mandated requirement for test validation in veterinary medicine and, while many of these assays have been shown to be capable of detecting equine troponin, the wide diversity of available tests, lack of validation, absence of protocols for their use and lack of standardisation make their application problematic. The objective of this review article is to address this issue, offering guidance where data are available and encouraging caution where there are none. Ultimately, the overall goal of this review is to examine critically the use of troponin assays in the horse and to promote the accurate and appropriate interpretation of valid results. PMID- 24215570 TI - Few-layer graphene shells and nonmagnetic encapsulates: a versatile and nontoxic carbon nanomaterial. AB - In this work a simple and scalable approach to coat nonmagnetic nanoparticles with few-layer graphene is presented. In addition, the easy processing of such nanoparticles to remove their core, leaving only the 3D graphene nanoshell, is demonstrated. The samples are comprehensively characterized, as are their versatility in terms of functionalization and as a material for electrochemical storage. Indeed, these 3D graphene nanostructures are easily functionalized much as is found with carbon nanotubes and planar graphene. Electrochemical investigations indicate these nanostructures are promising for stable long-life battery applications. Finally, initial toxicological investigations suggest no acute health risk from these 3D graphene nanostructures. PMID- 24215571 TI - Psychometric properties and validation of the Polish CP QOL-Child questionnaire: a pilot study. AB - AIM: Translate, determine the psychometric properties and validate the Polish CP QOL-Child questionnaire. MATERIALS AND METHODS: A double translation of the questionnaire from English into Polish and back was executed. The questionnaire was distributed to 55 parents/legal guardians of children with cerebral palsy aged 4-12 years. The psychometric properties of the questionnaire were determined on the basis of its internal consistency and the internal consistency of each of the investigated aspects, as well as on the assessment of the relationship between quality of life and such data as child's age, parent's age, place of residence and GMFCS level. RESULTS: The results showed high levels of internal consistency of the Polish version of the CP QOL-Child questionnaire - Cronbach's alpha was between 0.77 and 0.82, which is comparable to the original scale, where it was 0.74-0.92. In addition, we found no relationship between child's age and parent's age and the child's quality of life. Whereas we determined dependencies between the child's GMFCS level and quality of life in areas such as emotional state (p = 0.025), pain and the effects of disability (p = 0.033), and to a lesser extent participation in social life (p = 0.045). However, Spearman test presented that only domain pain and impact of disability reported positive correlation r = 0.43. CONCLUSION: Studies showed that English language the CP QOL Child questionnaire was successful translated into Polish which is confirmed by the results of the assessment of the psychometric properties and validation of the Polish language questionnaire. The results of our study indicate that the Polish language version of the CP QOL-Child questionnaire is an appropriate tool to assess the quality of life of Polish-speaking children with cerebral palsy aged 4-12 years. PMID- 24215572 TI - Quantifying on-road emissions from gasoline-powered motor vehicles: accounting for the presence of medium- and heavy-duty diesel trucks. AB - Vehicle emissions of nitrogen oxides (NOx), carbon monoxide (CO), fine particulate matter (PM2.5), organic aerosol (OA), and black carbon (BC) were measured at the Caldecott tunnel in the San Francisco Bay Area. Measurements were made in bore 2 of the tunnel, where light-duty (LD) vehicles accounted for >99% of total traffic and heavy-duty trucks were not allowed. Prior emission studies conducted in North America have often assumed that route- or weekend-specific prohibitions on heavy-duty truck traffic imply that diesel contributions to pollutant concentrations measured in on-road settings can be neglected. However, as light-duty vehicle emissions have declined, this assumption can lead to biased results, especially for pollutants such as NOx, OA, and BC, for which diesel engine emission rates are high compared to corresponding values for gasoline engines. In this study, diesel vehicles (mostly medium-duty delivery trucks with two axles and six tires) accounted for <1% of all vehicles observed in the tunnel but were nevertheless responsible for (18 +/- 3)%, (22 +/- 6)%, and (45 +/- 8)% of measured NOx, OA, and BC concentrations. Fleet-average OA and BC emission factors for light-duty vehicles are, respectively, 10 and 50 times lower than for heavy-duty diesel trucks. Using measured emission factors from this study and publicly available data on taxable fuel sales, as of 2010, LD gasoline vehicles were estimated to be responsible for 85%, 18%, 18%, and 6% of emissions of CO, NOx, OA, and BC, respectively, from on-road motor vehicles in the United States. PMID- 24215573 TI - Influence of orthostasis and daytime on retinal thickness in uveitis-associated cystoid macular edema. AB - AIM: To identify influence of orthostasis and daytime on retinal-thickness in cystoid-macular-edema (CME) using SD-OCT. METHODS: In this cross-sectional study 18 eyes with uveitis-associated CME (uvCME) were included. Orthostatic-changes of retinal-thickness were analyzed using a CirrusTM SD-OCT. Retinal-thickness was measured with patients lying horizontally on their side, followed by a fast sitting-up and OCT-measurement in sitting-position. Diurnal-change in thicknesses were assessed by SpectralisTM OCT between 8 AM and 8 PM. RESULTS: Approximately 20 s elapsed between position-change and the following OCT-measurement. In horizontal-position, the mean central retinal thickness (CRT) was 496 +/- 37 um, in upright position, the mean CRT was reduced to 412 +/- 43 um (p=0.032), thus position-change led to a 17% decrease in CRT. None of the other ETDRS-subfields showed a statistically significant decrease in thicknesses (p>0.05). In the second experiment, diurnal-CRT decreased over time, whereas the main decrease happened in the morning (8 a.m. 559 +/- 35 um, 12 p.m. 533 +/- 36 um, 4 p.m. 538 +/- 32 um, 8 p.m.551 +/- 38 um, p=0.01). Thicknesses in all other ETDRS-subgrids did not decrease statistically significantly. CONCLUSIONS: Intraretinal-fluid in uvCME may show a high mobility: CRT decreases within seconds after a patient changes position, indicating that position effects retinal-thickness. Main diurnal-decrease in CRT occurs before noon, which is likely due to a position change in the morning. Patient-population (walk-in patients versus hospitalized, lying patients) and previous waiting-position should be considered when interpreting retinal-thickness in clinical-practice. PMID- 24215574 TI - Reduction in hospital reattendance due to improved preoperative patient education following hemorrhoidectomy. AB - INTRODUCTION: To improve quality of healthcare, patient information must be thorough and easy to understand. This is important in day surgery where patients are seen less often by health practitioners. We looked at the impact of improving patient information in the setting of day-case hemorrhoidectomy in terms of patient satisfaction and whether medical attention was sought after the operation. METHODS: A retrospective, comparative study was performed on 60 patients undergoing day-case hemorrhoidectomy and on 60 patients undergoing the same operation with improved patient information. Comparisons were made between the groups regarding patient satisfaction scores, those seeking medical attention, the numbers of patients requesting a 6-week outpatient follow-up and the reasons for seeking medical advice. RESULTS: There was a significant improvement in the patient satisfaction scores in the second study group who received the improved information. This group sought medical attention significantly less and they felt less need for a routine follow-up. CONCLUSIONS: This study has shown that by improving the quality of patient information for day case hemorrhoidectomy, patient satisfaction was higher and fewer patients sought medical attention, which has beneficial financial indications for the NHS Trust and improvement of healthcare for the patient. PMID- 24215575 TI - Amygdala opioid receptors mediate the electroacupuncture-induced deterioration of sleep disruptions in epilepsy rats. AB - BACKGROUND: Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control. Effects of acupuncture of Feng-Chi (GB20) acupoints on epilepsy suppression and insomnia treatment have been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot). Therefore, this study was designed to investigate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi acupoints on sleep disruptions in rats with focal epilepsy. RESULTS: Our result indicates that administration of pilocarpine into the left central nucleus of amygdala (CeA) induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non REM (NREM) sleep. High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints, in which a 30-min EA stimulation was performed before the dark period of the light:dark cycle in three consecutive days, further deteriorated pilocarpine-induced sleep disruptions. The EA-induced exacerbation of sleep disruption was blocked by microinjection of naloxone, MU- (naloxonazine), kappa- (nor-binaltorphimine) or delta-receptor antagonists (natrindole) into the CeA, suggesting the involvement of amygdaloid opioid receptors. CONCLUSION: The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints exhibits no benefit in improving pilocarpine-induced sleep disruptions; in contrast, EA further deteriorated sleep disturbances. Opioid receptors in the CeA mediated EA-induced exacerbation of sleep disruptions in epileptic rats. PMID- 24215576 TI - Preoperative serum CA 72.4 as prognostic factor of recurrence and death, especially at TNM stage II, for colorectal cancer. AB - BACKGROUND: Nowadays, evaluation of colorectal cancer prognosis and decision making for treatment continues to be based primarily on TNM tumour stage. Administration of adjuvant chemotherapy is especially challenging for stage II patients that can have very different disease-related outcomes. Therefore, more reliable prognostic markers need to be developed to improve the selection of stage II patients at high risk for recurrence. Our purpose is to assess the prognostic value of preoperative serum CA 72.4 to improve the risk stratification of CRC patients. METHODS: Preoperative sera collected from 71 unselected patients between January 1994 and February 1997 was assayed for CA 72.4 and CEA levels. Patients were followed-up for at least 30 months or until relapse. Survival curves were estimated by the Kaplan-Meier method and the prognostic value was determined using Log-Rank test and Cox regression analysis. RESULTS: Preoperative CA 72.4 levels above 7 U/mL correlate with a worse prognosis, with associated recurrence and death percentages exceeding the displayed by CEA. In a multivariate analysis, its combination with CEA proved the most important independent factor predicting survival. Remarkably, at stage II CA 72.4 also discriminates better than CEA those patients that will relapse or die from those with a favourable prognosis; however, CEA has not a negligible effect on survival. CONCLUSIONS: The most outstanding finding of the present work is the correct classification of nearly every patient with bad prognosis (relapse or death) at TNM stage II when CEA and CA 72.4 are used altogether. This could improve the decision-making involved in the treatment of stage II colon cancer. Certainly further large-scale studies must be performed to determine whether CA 72.4 can be effectively used in the clinical setting. PMID- 24215577 TI - Acute and long-term management of food allergy: systematic review. AB - BACKGROUND: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized. RESULTS: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1 antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration. CONCLUSIONS: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority. PMID- 24215578 TI - What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? AB - This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and beta-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to beta-adrenergic blockers and ACEI are attenuated. Available data are very limited but self defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit. PMID- 24215579 TI - Risk factors of postoperative urinary retention after hip surgery for femoral neck fracture in elderly women. AB - AIM: The aim of the present study was to evaluate risk factors for postoperative urinary retention (POUR) in female patients with femoral neck fractures. METHODS: We recruited 72 female patients (age 86.5 +/- 6.7 years) from among 90 cases of hip surgery carried out between January and December 2011 at Goto Chuo Hospital. We evaluated the risk factors for POUR, including the administration of anticholinergic drugs, diabetes mellitus, preoperative dementia and/or delirium, neurological disorders, age, hypertension, overactive bladder, and the postoperative duration of the use of an indwelling urethral catheter using a multiple logistic regression analysis. RESULTS: In the present study, POUR occurred in eight out of 72 cases (11.1%). The multivariate analysis showed that the indwelling period of the urethral catheter (per 1-day increase; P = 0.04, OR 0.33 95% CI 0.11-0.96), and preoperative dementia and/or delirium (P = 0.03, OR10.4, 95%CI 1.21-89.2) correlated with the occurrence of POUR. Diabetes mellitus (P = 0.78), anticholinergic agents (P = 0.23), neurological disorders (P = 0.83), age (P = 0.86), hypertension (P = 0.76) and overactive bladder (P = 0.34) did not significantly correlate with the occurrence of POUR. CONCLUSIONS: The present study showed that the early removal of the urethral catheter, and preoperative dementia and/or delirium had significant correlations with POUR. The femoral neck fractures and the surgical procedure used for the hip surgery do not induce damage to the bladder and nerve system related to the voiding function, and the voiding function in all of the patients recovered after short-term intermittent catheterization. Physicians should not place permanent indwelling urethral catheters without carrying out urological assessments. PMID- 24215580 TI - Steric-induced effects on stabilizing a lamellar structure. AB - We investigate the behavior of multilamellar phases composed of lecithin and a commercial cosurfactant (Simusol), which is a mixture of ethoxylated fatty acids. Using X-ray scattering and a new procedure to fit the data, relevant parameters characterizing the lamellar structure were determined as a function of membrane composition, varying from 100% of lecithin to 100% of Simulsol. Scattering data illustrating the swelling of the lamellae for different amounts of cosurfactant are presented with the respective behavior of the Caille parameter. With this experimental approach, we show that the incorporation of ethoxy brushes onto the lipid surface enhances repulsive interactions arising from membrane fluctuations and changes the interactions at the interface between bilayers. PMID- 24215581 TI - Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel. AB - Paclitaxel (PAC) is an anticancer drug that has been shown to generate free radicals leading to irreversible cell injury. Vitamin B12 has antioxidative properties and can protect DNA from free radicals. In this study, we examined the possible genotoxic effect of PAC on DNA as well as the possible protective effect of vitamin B12 on DNA damage induced by paclitaxel. Sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured in cultured human blood lymphocytes treated with PAC (10 uM) and/or vitamin B12 (2.7 mg/mL). Our results showed that PAC significantly increased the frequencies of SCEs (p < 0.001) and CAs (p < 0.001) in human blood lymphocytes, as compared to controls. These DNA damages, caused by PAC drug, were prevented by pretreatment of cells with vitamin B12. In addition, we showed that PAC induced an increase in 8-OHdG, a marker of oxidative DNA damage, and that this increase was prevented by vitamin B12. Vitamin B12 seems to protect against genotoxicity induced by PAC in human blood lymphocytes. PMID- 24215582 TI - Obstetricians' attitudes and beliefs regarding umbilical cord clamping. AB - OBJECTIVE: Although delayed umbilical cord clamping has been demonstrated to reduce the incidence of intraventricular hemorrhage and neonatal sepsis, and decrease the need for neonatal transfusions (without affecting cord pH, Apgar scores or the need for phototherapy), the extent to which this practice is being employed is unknown. We conducted a survey of US obstetricians to assess their attitudes and beliefs about cord clamping. STUDY DESIGN: Questionnaires were randomly mailed to members of the American College of Obstetricians and Gynecologists (ACOG), and the Collaborative Ambulatory Research Network (CARN). The data were analyzed using Chi-square and Student t tests. RESULTS: The response rates for the CARN and other ACOG members were 47% and 21%, respectively. Most (88%) responders reported their hospital had no umbilical cord clamping policy. The most frequent response for optimal timing of umbilical cord clamping, regardless of gestational age, was "don't know". Potential for neonatal red blood cell transfusion was the only concern cited as a reason for being somewhat or very inclined to delay umbilical cord clamping (51%). Delayed neonatal resuscitation (76%) was listed as a reason to clamp the cord immediately, despite the paucity of literature to support immediate cord clamping in this cohort. CONCLUSION: Despite substantial evidence supporting the practice of delayed cord clamping, few institutions have policies regarding this practice. Moreover, obstetricians' beliefs about the appropriate timing for umbilical cord clamping are not consistent with the evidence that demonstrates its beneficial impact on neonatal outcomes. PMID- 24215583 TI - Room temperature self-healing thermoset based on the Diels-Alder reaction. AB - A self-healing epoxy-amine thermoset based on the compatible functionalization of the thermoset and encapsulated healing agent has been successfully developed. Healing of the thermoset resulted from the reaction of furans in the thermoset and multimaleimides (MMIs) in the healing agent solution. The healing agent, MMI dissolved in phenyl acetate, was encapsulated using a urea-formaldehyde encapsulation method. Autonomic healing of the thermoset was achieved by incorporating microcapsules filled with the healing agent solution within a furan functionalized epoxy-amine thermoset. The resulting self-healing thermoset recovered 71% of its initial load after fracture. PMID- 24215584 TI - Development of a new modelling tool (FACET) to assess exposure to chemical migrants from food packaging. AB - The approach used to obtain European Union-wide data on the usage and concentration of substances in different food packaging materials is described. Statistics were collected on pack sizes and market shares for the different materials used to package different food groups. The packaging materials covered were plastics (both flexible and rigid), metal containers, light metal packaging, paper and board, as well as the adhesives and inks used on them. An explanation as to how these data are linked in various ways in the FACET exposure modelling tool is given as well as an overview of the software along with examples of the intermediate tables of data. The example of bisphenol A (BPA), used in resins that may be incorporated into some coatings for canned foodstuffs, is used to illustrate how the data in FACET are combined to produce concentration distributions. Such concentration distributions are then linked probabilistically to the amounts of each food item consumed, as recorded in national food consumption survey diaries, in order to estimate exposure to packaging migrants. Estimates of exposure are at the level of the individual consumer and thus can be expressed for various percentiles of different populations and subpopulations covered by the national dietary surveys. PMID- 24215586 TI - Understanding self-awareness in palliative care. AB - Exploring the spiritual and psychological realms is more difficult than simply addressing the physical dimension of palliative care. Knowing oneself is essential to align one's work within the hospice philosophy. Giving and receiving love are equally important. This case study examines importance of self-awareness in managing escalating suffering at the end of life. PMID- 24215585 TI - Integrated electroosmotic perfusion of tissue with online microfluidic analysis to track the metabolism of cystamine, pantethine, and coenzyme A. AB - We have developed an approach that integrates electroosmotic perfusion of tissue with a substrate-containing solution and online microfluidic analysis of products, in this case thiols. Using this approach we have tracked the metabolism of cystamine, pantethine and CoA in the extracellular space of organotypic hippocampal slice cultures (OHSCs). Currently, little is known about coenzyme A (CoA) biodegradation and even less is known about the regulation and kinetic characteristics for this sequential multienzyme reaction. We found that the steady state percentage yields of cysteamine from cystamine and pantethine during the transit through OHSCs were 91% +/- 4% (SEM) and 0.01%-0.03%, respectively. The large difference in the yields of cysteamine can be used to explain the drugs' different toxicities and clinical effectiveness against cystinosis. The kinetic parameters of the enzyme reaction catalyzed by the ectoenzyme pantetheinase are KM,C/alpha = 4.4 +/- 1.1 mM and Vmax,C = 29 +/- 3 nM/s, where alpha is the percentage yield of pantethine to pantetheine through disulfide exchange. We estimate that the percentage yield of pantethine to pantetheine through disulfide exchange is approximately 0.5%. Based on the formation rate of cysteamine in the OHSCs, we obtained the overall apparent Michaelis constant and maximum reaction rate for sequential, extracellular CoA degradation in an in situ environment, which are K'M = 16 +/- 4 MUM, V'max = 7.1 +/- 0.5 nM/s. Kinetic parameters obtained in situ, although difficult to measure, are better representations of the biochemical flux in the living organism than those from isolated enzymes in vitro. PMID- 24215587 TI - Canine oral mucosal mast cell tumours. AB - Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present. PMID- 24215589 TI - Rosiglitazone may reduce thyroid cancer risk in patients with type 2 diabetes. AB - BACKGROUND: Whether rosiglitazone use in patients with type 2 diabetes may affect thyroid cancer risk has not been investigated. METHODS: The reimbursement databases of all diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance of Taiwan. An entry date was set at 1 January 2006, and 887,665 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009 for ever-users, never-users, and subgroups of rosiglitazone exposure using tertile cut-offs for time since starting rosiglitazone, duration of therapy, and cumulative dose. Hazard ratios were estimated by Cox regression. RESULTS: There were 103,224 ever users and 784,441 never-users, with respective numbers of incident thyroid cancer of 84 (0.08%) and 764 (0.10%), and respective incidence of 23.12 and 28.09 per 100,000 person-years. The overall multivariable-adjusted hazard ratio was not significant. However, in dose-response analyses, the adjusted hazard ratios (95% confidence intervals) were significant for the third tertile of duration of therapy (>= 14 months) and cumulative dose (>= 1,800 mg) for age >= 50 years: 0.53 (0.31-0.89) and 0.50 (0.29-0.87), respectively. CONCLUSIONS: This study suggests that rosiglitazone use in patients with type 2 diabetes may reduce the risk of thyroid cancer. PMID- 24215590 TI - State-of-the-art high-speed atomic force microscopy for investigation of single molecular dynamics of proteins. PMID- 24215588 TI - Reconciliation of chemical, enzymatic, spectroscopic and computational data to assign the absolute configuration of the DNA base lesion spiroiminodihydantoin. AB - The diastereomeric spiroiminodihydantoin-2'-deoxyribonucleoside (dSp) lesions resulting from 2'-deoxyguanosine (dG) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (dOG) oxidation have generated much attention due to their highly mutagenic nature. Their propeller-like shape leads these molecules to display mutational profiles in vivo that are stereochemically dependent. However, there exist conflicting absolute configuration assignments arising from electronic circular dichroism (ECD) and NOESY-NMR experiments; thus, providing definitive assignments of the 3D structure of these molecules is of great interest. In the present body of work, we present data inconsistent with the reported ECD assignments for the dSp diastereomers in the nucleoside context, in which the first eluting isomer from a Hypercarb HPLC column was assigned to be the S configuration, and the second was assigned the R configuration. The following experiments were conducted: (1) determination of the diastereomer ratio of dSp products upon one electron oxidation of dG in chiral hybrid or propeller G-quadruplexes that expose the re or si face to solvent, respectively; (2) absolute configuration analysis using vibrational circular dichroism (VCD) spectroscopy; (3) reinterpretation of the ECD experimental spectra using time-dependent density functional theory (TDDFT) with the inclusion of 12 explicit H-bonding waters around the Sp free bases; and (4) reevaluation of calculated specific rotations for the Sp enantiomers using the hydration model in the TDDFT calculations. These new insights provide a fresh look at the absolute configuration assignments of the dSp diastereomers in which the first eluting from a Hypercarb-HPLC column is (-) (R)-dSp and the second is (+)-(S)-dSp. These assignments now provide the basis for understanding the biological significance of the stereochemical dependence of enzymes that process this form of DNA damage. PMID- 24215591 TI - Muscle disuse atrophy is not accompanied by changes in skeletal muscle satellite cell content. AB - Muscle disuse leads to a considerable loss in skeletal muscle mass and strength. However, the cellular mechanisms underlying disuse-induced muscle fibre atrophy remain to be elucidated. Therefore we assessed the effect of muscle disuse on the CSA (cross-sectional area), muscle fibre size, satellite cell content and associated myocellular signalling pathways of the quadriceps muscle. A total of 12 healthy young (24+/-1 years of age) men were subjected to 2 weeks of one legged knee immobilization via a full-leg cast. Before and immediately after the immobilization period and after 6 weeks of natural rehabilitation, muscle strength [1RM (one-repetition maximum)], muscle CSA [single slice CT (computed tomography) scan] and muscle fibre type characteristics (muscle biopsies) were assessed. Protein and/or mRNA expression of key genes [i.e. MYOD (myogenic differentiation), MYOG (myogenin) and MSTN (myostatin)] in the satellite cell regulatory pathways were determined using Western blotting and RT-PCR (real-time PCR) analyses respectively. The present study found that quadriceps CSA declined following immobilization by 8+/-2% (P<0.05). In agreement, both type I and type II muscle fibre size decreased 7+/-3% and 13+/-4% respectively (P<0.05). No changes were observed in satellite cell content following immobilization in either type I or type II muscle fibres. Muscle MYOG mRNA expression doubled (P<0.05), whereas MSTN protein expression decreased 30+/-9% (P<0.05) following immobilization. Muscle mass and strength returned to the baseline values within 6 weeks of recovery without any specific rehabilitative programme. In conclusion, 2 weeks of muscle disuse leads to considerable loss in skeletal muscle mass and strength. The loss in muscle mass was attributed to both type I and type II muscle fibre atrophy, and was not accompanied by a decline in satellite cell content. PMID- 24215593 TI - Complete Vogt-Koyanagi-Harada disease and Holmes-Adie syndrome: case report. AB - We report a 37-year-old woman with uveitic phase of Vogt Koyanagi Harada disease and tonic pupil, the tonic pupil persisted after other clinical features of this syndrome had disappeared; neurological evaluation shows absent knee and arm tendon reflexes and positive cholinergic supersensitivity test with Pilocarpine 0.125% confirming the diagnosis of Holmes Adie Syndrome. PMID- 24215592 TI - Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. AB - BACKGROUND: Alternate day fasting (ADF; ad libitum "feed day", alternated with 25% energy intake "fast day"), is effective for weight loss and cardio-protection in obese individuals. Whether these effects occur in normal weight and overweight individuals remains unknown. This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects. METHODS: Thirty-two subjects (BMI 20-29.9 kg/m2) were randomized to either an ADF group or a control group for 12 weeks. RESULTS: Body weight decreased (P < 0.001) by 5.2 +/- 0.9 kg (6.5 +/- 1.0%) in the ADF group, relative to the control group, by week 12. Fat mass was reduced (P < 0.001) by 3.6 +/- 0.7 kg, and fat free mass did not change, versus controls. Triacylglycerol concentrations decreased (20 +/- 8%, P < 0.05) and LDL particle size increased (4 +/- 1 A, P < 0.01) in the ADF group relative to controls. CRP decreased (13 +/- 17%, P < 0.05) in the ADF group relative to controls at week 12. Plasma adiponectin increased (6 +/- 10%, P < 0.01) while leptin decreased (40 +/- 7%, P < 0.05) in the ADF group versus controls by the end of the study. LDL cholesterol, HDL cholesterol, homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment. CONCLUSION: These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached. PMID- 24215594 TI - A novel intermolecular synthesis of gamma-lactones via visible-light photoredox catalysis. AB - Direct gamma-lactone formation via visible-light photoredox catalysis has been achieved efficiently including hydroxylalkylation of aromatic alkenes and transesterification. The present photocatalytic protocol has good regioselectivity and substrate compatibility, affording a novel way to intermolecular gamma-lactone synthesis by the reaction of styrenes with alpha bromo esters in the absence of any external oxidants. PMID- 24215595 TI - Parental stress and dyadic consensus in early parenthood among mothers and fathers in Sweden. AB - BACKGROUND: Parental stress can negatively affect the parent-child relationship and reduce the well-being of the whole family. Family disagreement is associated with parental divorce and with psychological problems in children. AIMS: The aim was to examine perceived parental stress and draw comparisons among mothers and among fathers, in relation to educational level, parental experience, existence of a parental role model and sense of coherence. The aim was also to examine perceived dyadic consensus and its association with perceived parental stress within couples. METHODS: Questionnaires were completed by 320 mothers and 315 fathers at 1 week and 18 months post-partum. The Swedish Parenthood Stress Questionnaire, the Sense of Coherence Scale and the Dyadic Consensus Subscale were used. RESULTS: Low education, lack of a role model and poor sense of coherence promoted stress in mothers in the subareas social isolation and spouse relationship problems, while lack of a role model and poor sense of coherence promoted stress in fathers in the subarea social isolation. Furthermore, parental experiences promoted stress among mothers in the subarea incompetence while this was not seen among fathers. Mothers perceived a higher level of dyadic consensus than fathers in the items recreational activities, friends, aims and life goals, time spent together, and decisions regarding career and personal development. Household tasks was the only item where fathers perceived a higher level of dyadic consensus than mothers. Additionally, there were associations between perceived parental stress and dyadic consensus in several items and in the total score. CONCLUSIONS: To promote parents' health and family stability, health professionals should consider factors affecting stress and stress reactions, and take gender roles into account. PMID- 24215596 TI - Real-time monitoring of emissions from monoethanolamine-based industrial scale carbon capture facilities. AB - We demonstrate the capabilities and properties of using Proton Transfer Reaction time-of-flight mass spectrometry (PTR-ToF-MS) to real-time monitor gaseous emissions from industrial scale amine-based carbon capture processes. The benchmark monoethanolamine (MEA) was used as an example of amines needing to be monitored from carbon capture facilities, and to describe how the measurements may be influenced by potentially interfering species in CO2 absorber stack discharges. On the basis of known or expected emission compositions, we investigated the PTR-ToF-MS MEA response as a function of sample flow humidity, ammonia, and CO2 abundances, and show that all can exhibit interferences, thus making accurate amine measurements difficult. This warrants a proper sample pretreatment, and we show an example using a dilution with bottled zero air of 1:20 to 1:10 to monitor stack gas concentrations at the CO2 Technology Center Mongstad (TCM), Norway. Observed emissions included many expected chemical species, dominantly ammonia and acetaldehyde, but also two new species previously not reported but emitted in significant quantities. With respect to concerns regarding amine emissions, we show that accurate amine quantifications in the presence of water vapor, ammonia, and CO2 become feasible after proper sample dilution, thus making PTR-ToF-MS a viable technique to monitor future carbon capture facility emissions, without conventional laborious sample pretreatment. PMID- 24215597 TI - Hypervalent iodine reagent mediated reaction of [60]fullerene with amines. AB - The hypervalent iodine reagent mediated reaction of C60 with various readily available amines for the easy preparation of iminofullerenes has been developed. The reaction between C60 and sulfonamides can be effectively controlled to selectively synthesize azafulleroids or aziridinofullerenes under PhI(OAc)2/I2 or PhIO/I2/CuCl/lutidine conditions, respectively. For phosphamide and urea, only one isomer is obtained. However, carbamate gives three kinds of products. Interestingly, the reaction of C60 with alkylamines allows the effective synthesis of aziridinofullerenes and regioselective cis-1-bisaziridinofullerenes. PMID- 24215598 TI - Epitaxial Bi5Ti3FeO15-CoFe2O4 pillar-matrix multiferroic nanostructures. AB - Epitaxial self-assembled ferro(i)magnetic spinel (CoFe2O4 (CFO)) and ferroelectric bismuth layered perovskite (Bi5Ti3FeO15 (BTFO)) pillar-matrix nanostructures are demonstrated on (001) single-crystalline strontium titanate substrates. The CFO remains embedded in the BTFO matrix as vertical pillars (~50 nm in diameter) up to a volume fraction of 50%. Piezoresponse force microscopy experiments evidence a weak out-of-plane and a strong in-plane ferroelectricity in the BTFO phase, despite previously reported paraelectricity along the c-axis in a pure BTFO film. Phenomenological Landau-Ginzburg-Devonshire-based thermodynamic computations show that the radial stress induced by the CFO nanopillars can influence these ferroelectric phases, thus signifying the importance of the nanopillars. The CFO pillars demonstrate robust ferromagnetic hysteresis loops with little degradation in the saturation magnetization (ca. 4 MUB/f.u.). Thus BTFO-CFO nanocomposites show significant promise as a lead-free magnetoelectric materials system. PMID- 24215599 TI - In vivo validation of the new Tonopen AVIA tonometer using manometers placed in the anterior chamber and the vitreous cavity under various vitreous conditions. AB - PURPOSE: To validate intraocular pressure (IOP) measurements using the new Tonopen AVIA(r) tonometer by comparing values obtained with those measured by manometers placed in the anterior chamber (AC) and the vitreous cavity (VC). MATERIALS AND METHODS: Seventy-nine consecutive patients awaiting phacovitrectomy for epiretinal membrane (ERM) or macular hole (MH) (n=29), vitreous hemorrhage (DMVH) (n=27) or silicone oil removal (n=23) were included in this prospective observational study. A clinician masked to patient information performed a complete ophthalmologic examination, including measurements of corneal thickness (CT), AC depth and axial length. Another examiner simultaneously measured conventional IOP using the Tonopen AVIA(r) (TIOP) and AC and VC IOPs (ACIOP and VCIOP) using two transducers. RESULTS: The mean TIOP, ACIOP and VCIOP were 16.1 +/- 3.8, 16.1 +/- 4.4 and 15.5 +/- 4.6 mmHg, respectively. There was a good agreement between the TIOP and ACIOP; however, the agreement between TIOP and VCIOP was relatively poor in subgroup analysis. VCIOP was significantly higher than TIOP in the ERM and MH group, with a mean difference of 1.0 mmHg (p=0.042); however, they were significantly lower in the DMVH group, with a mean difference of -0.7 mmHg (p=0.026) and in the silicone oil group (mean difference, -2.3 mmHg) (p<0.0001). In multivariate analysis, TIOP correlated significantly only with CT (p<0.037) and increased by 2.7 mmHg per 100 MUm increase in CT. CONCLUSIONS: IOP measurements using the Tonopen AVIA(r) tonometer showed good agreement with ACIOP values, although TIOP measurements were affected by CT. However, the VCIOP values using the transducer may have over- or underestimated IOP relative to TIOP and ACIOP under various vitreous conditions. Further validation of VCIOP using a cannular type of manometer should be considered. PMID- 24215600 TI - Arthrogryposis in infancy, multidisciplinary approach: case report. AB - BACKGROUND: Arthrogryposis multiplex congenita is an etiopathogenetically heterogeneous disorder characterised by non-progressive multiple intra-articular contractures, which can be recognised at birth. The frequency is estimated at 1 in 3,000 newborns. Etiopathogenesis of arthrogryposis is multifactorial. CASE PRESENTATION: We report first 26 weeks of life of a boy with severe arthrogryposis. Owing to the integrated rehabilitation approach and orthopaedic treatment a visible improvement in the range of motion as well as the functionality of the child was achieved. This article proposes a cooperation of various specialists: paediatrician, orthopaedist, specialist of medical rehabilitation and physiotherapist. CONCLUSIONS: Rehabilitation of a child with arthrogryposis should be early, comprehensive and multidisciplinary. Corrective treatment of knee and hip joints in infants with arthrogryposis should be preceded by the ultrasound control. There are no reports in the literature on the ultrasound imaging techniques which can be used prior to the planned orthopaedic and rehabilitative treatment in infants with arthrogryposis. The experience of our team indicates that such an approach allows to minimise the diagnostic errors and to maintain an effective treatment without the risk of joint destabilisation. PMID- 24215601 TI - Advanced method for evaluation of gastric cancer risk by serum markers: determination of true low-risk subjects for gastric neoplasm. AB - BACKGROUND: Patients with negative anti-Helicobacter pylori antibody titer and high pepsinogen (PG) level (group A) are regarded as having a low risk for gastric cancer. However, gastric cancer cases are occasionally observed in this group. We aimed to elucidate the clinical features of gastric neoplasm in group A patients and reviewed advanced methods for mass screening. MATERIALS AND METHODS: A total of 271 gastric epithelial neoplasm patients were enrolled. We classified them according to the H. pylori-PG system and determined the number of patients in each group. After excluding true H. pylori-negative cases from group A (group A'), we examined the differences between group A' and group non-A. RESULTS: Group A included 30 (11%) patients, and only three of these were true negative for H. pylori. All patients in group A' (n = 27) exhibited endoscopic atrophy in the gastric corpus. Serologically, these patients showed low gastrin, low PG II and high PG I/II ratio, indicative of post-eradication. Histologically, 24 (89%) of these had little inflammation, and 26 (96%) were negative for H. pylori by immunohistochemistry. No difference was observed in the incidence of metachronous gastric tumors between group A' and group non-A. The discriminant function using gastrin and PGs could distinguish these 27 patients from true H. pylori-negative controls with 85% sensitivity and 84% specificity. CONCLUSIONS: Group A included a certain number of patients with atrophic gastritis who were potentially at risk of gastric neoplasm development. Although evaluation of corpus atrophy is necessary for the identification of these patients, the discriminant function may be useful. PMID- 24215602 TI - LysoTracker is a marker of differentiated alveolar type II cells. AB - BACKGROUND: LysoTracker Green DND-26 is a fluorescent dye that stains acidic compartments in live cells and has been shown to selectively accumulate in lamellar bodies in alveolar type II (AT2) cells in the lung. The aim of this study was to determine whether the accumulation of LysoTracker in lamellar bodies can be used to isolate viable AT2 cells by flow cytometry and track their differentiation in live-cell culture by microscopy. METHODS: Mouse lung cells were sorted on the basis of CD45(neg)CD31(neg)EpCAM(pos)LysoTracker(pos) expression and characterized by immunostaining for SP-C and cultured in a three dimensional epithelial colony-forming unit (CFU-Epi) assay. To track AT2 cell differentiation, lung epithelial stem and progenitor cells were cultured in a CFU Epi assay with LysoTracker-supplemented media. RESULTS: The purity of sorted AT2 cells as determined by SP-C staining was 97.4% and viability was 85.3%. LysoTracker(pos) AT2 cells generated SP-C(pos) alveolar epithelial cell colonies in culture, and when added to the CFU-Epi culture medium, LysoTracker marked the differentiation of stem/progenitor-derived AT2 cells. CONCLUSIONS: This study describes a novel method for isolating AT2 cells from mouse lungs. The high purity and viability of cells attained by this method, makes them suitable for functional analysis in vitro. The application of LysoTracker to live cell cultures will allow better assessment of the cellular and molecular mechanisms that regulate AT2 cell differentiation. PMID- 24215603 TI - Association of knee-extension strength with instrumental activities of daily living in community-dwelling older adults. AB - AIM: The purpose of the present study was to investigate the relationship between knee-extension (KE) strength and instrumental activities of daily living (IADL), and to examine the risk of IADL disability in relation to KE strength in community-dwelling older adults. METHODS: The participants were 1235 community dwelling older adults (261 men and 974 women) in Tokyo who underwent a comprehensive health survey in 2009. The health survey included measurement of KE strength and a questionnaire on the Tokyo Metropolitan Institute of Gerontology (TMIG)-IADL. Pearson product-moment correlation coefficients and partial correlation coefficients were calculated separately for each sex for four parameters representing quadriceps muscle strength and TMIG-IADL. Pearson's chi(2)-test of independence and the Cochran-Armitage test of trend were also carried out to determine the relationship between KE strength and IADL disability. RESULTS: In women, all correlations between the quadriceps muscle strength parameters and the TMIG-IADL score were statistically significant (P < 0.0005). The significance persisted remained even after factors regarding cognition or depression were taken into consideration. Furthermore, the percentage of female participants with IADL disability was dependent on KE strength; there was an inverse trend between KE strength and the percentage of people with IADL disability. In men, no significant relationship was found between KE strength and IADL. CONCLUSIONS: KE strength and IADL correlated positively, and the percentage of people with IADL disability decreased with increasing KE strength in women. PMID- 24215604 TI - Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats. AB - Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs. PMID- 24215606 TI - Fabrication of high-quality VO2 thin films by ion-assisted dual ac magnetron sputtering. AB - The technique of cathodic ac dual magnetron sputtering along with the high energy ionic bombardment is known to yield high-quality thin films in terms of their uniformity and high density. This technique has been applied for the first time to achieve thermochromic VO2 thin films that show a high optical and electrical contrast between normal and switched states. In this two-step process Vanadium metal films were deposited and subsequently oxidized in optimum conditions to achieve stoichiometric VO2 films. Typical films switched between more than 40 % to less than 5 % transmission in the infrared region while undergoing an electrical sheet resistance change between 1 * 10(5) and 1 * 10(2) Omega/cm(2). The application potential of such VO2 films in integrated optics is deemed high. PMID- 24215605 TI - Optimal use of phosphate binders in chronic kidney disease. AB - INTRODUCTION: Hyperphosphatemia is one of the major factors associated with the development of vascular calcification in patients with chronic kidney disease (CKD). Since phosphate is retained in such patients, pharmacological treatment and other measures are necessary to control hyperphosphatemia. Several phosphate binders (calcium salts, magnesium salts, non-calcium-based binders and aluminium) are available for the treatment of hyperphosphatemia. Nevertheless, none of the above mentioned agents has shown an overall superiority over others, while potency and side effects are quite variable among them creating difficulties in choosing the optimal drug for each patient. AREAS COVERED: The authors discuss the disturbed phosphate metabolism, the available phosphate binders, as well as the general therapeutic principles of treating hyperphosphatemia in CKD patients. The literature used for this review had been retrieved from PubMed and covers a large number of original and retrospective studies as well as prospective cohort studies, meta-analyses and international clinical guidelines. EXPERT OPINION: Lowering serum phosphate levels in CKD patients may potentially have a positive impact on cardiovascular morbidity and mortality. Factors that should be taken into consideration when selecting a specific drug include CKD stage, cardiovascular disease, severity of secondary hyperparathyroidism, concomitant medications, life expectancy and patient compliance. Therefore, when selecting a specific phosphate binder, individualisation is mandatory. PMID- 24215607 TI - Outcomes of tracheostomy in the neonatal intensive care unit: is there an optimal time? AB - OBJECTIVE: To compare short-term outcomes of infants who underwent early versus late tracheostomy during their initial hospitalization after birth and determine the association, if any, between tracheostomy timing and outcomes. STUDY DESIGN: Retrospective chart review of infants who underwent a tracheostomy during their initial hospitalization at a single site. RESULTS: The median (range) gestational age of our cohort (n = 127) was 28 (23-42) weeks and birth weight was 988 (390 4030) g. Tracheostomy indications included airway lesions (47%), bronchopulmonary dysplasia (25%), both (22%) and others (6%). Median postmenstrual age (PMA) at tracheostomy was 45 (35-75) weeks. Death occurred in 27 (21%) infants and 65 (51%) infants were mechanically ventilated. G-tube was present at discharge in 42 (33%) infants. Infants who underwent early tracheostomy (<45 weeks PMA) (n = 66) had significantly lower gestational ages, weights and respiratory support than the late (>=45 weeks PMA) (n = 61) group. Death (29.5% versus 14%), home ventilation (41% versus 21%) and G tube (44% versus 14%) were significantly more frequent in the late tracheostomy group. On bivariate regression, outcomes were not independently associated with tracheostomy timing, after adjustment for gestational age and respiratory support. CONCLUSIONS: Of infants who underwent tracheostomy during the initial hospitalization after birth, 21% died. On adjusted analysis, tracheostomy timing was not independently associated with outcomes. PMID- 24215608 TI - Cocrystals of nicotinamide and (R)-mandelic acid in many ratios with anomalous formation properties. AB - We report a remarkable system of cocrystals containing nicotinamide (NIC) and (R) mandelic acid (RMA) in numerous stoichiometric ratios (4:1, 1:1 in two polymorphs, and 1:2) with anomalous formation properties. The formation of these cocrystals decreases energy but expands volume, in contrast to most physical processes, but similar to water freezing. The decrease of energy upon cocrystallization agrees with the exothermic mixing of NIC and RMA liquids (a base and an acid). Volume expansion is general for the formation of all NIC cocrystals for which data exist (n = 40): +3.9 A(3)/molecule or +17 cm(3)/kg on average, corresponding to a 2% expansion. This volume expansion correlates with the shortening and strengthening of hydrogen bonds upon cocrystallization, analogous to water freezing. The NIC-RMA binary phase diagram was constructed that contains the congruent and incongruent melting of six crystalline phases. These results are relevant for understanding the nature of cocrystallization and why some molecules are prolific cocrystal formers. PMID- 24215609 TI - Antimicrobial resistance in Staphylococcus aureus, Streptococcus uberis and Streptococcus dysgalactiae from dairy cows with mastitis. AB - AIMS: To determine the minimal inhibitory concentrations (MIC) of antimicrobials for common mastitis pathogens from dairy cows in New Zealand; and to assess the effect of source of the isolates, i.e. commercial veterinary laboratories or collected as part of research studies; the clinical status of the cow, i.e. subclinical or clinical mastitis; cow age and herd on the distribution of the MIC. METHODS: Minimal inhibitory concentrations for Staphylococcus aureus (n=364), Streptococcus dysgalactiae (n=65) and Streptococcus uberis (n=102) isolated from milk samples from dairy cows were determined for a variety of antimicrobials using broth microdilution. Isolates of S. aureus were sourced from research studies from both subclinically (n=161) and clinically (n=104) affected cows, as well as from commercial veterinary laboratories (n=101); while all the streptococcal isolates were from commercial laboratories. Resistance was defined using the cut-points provided by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: The distribution of MIC varied among the bacterial species for every antimicrobial tested (p<0.001). Of the S. aureus isolates, 28, 2 and 0.5% were resistant to penicillin, ampicillin and trimethoprim/sulfamethoxazole, respectively. For S. dysgalactiae and S. uberis isolates, 17 and 13% were resistant to trimethoprim/sulfamethoxazole, respectively. One isolate (1%) of S. uberis was resistant to penicillin. The distribution of MIC of S. aureus varied with clinical status, between herds, and with age of cow (p<0.05). The distribution of MIC for S. aureus for penicillin, amoxicillin/clavulanic acid, cloxacillin and ampicillin were lower from clinical than subclinical cases, and those for amoxicillin/clavulanic acid and oxytetracycline from isolates from veterinary laboratories were lower than for those from research studies. CONCLUSIONS: Resistance to some beta-lactam antimicrobials and trimethoprim/sulfamethoxazole were found in isolates from cases of bovine mastitis. The distribution of MIC for isolates of S. aureus varied with clinical status of the cow, the age of the cow, the herd and with the source of isolate. CLINICAL SIGNIFICANCE: Resistance to penicillin was found in a quarter of S. aureus isolates, but in virtually no Streptococcus isolates; therefore microbial identification and sensitivity testing would be beneficial when assessing treatment options. The source of the isolates affected the estimated MIC, suggesting that selection of isolates for monitoring of resistance requires care and that use of routine submissions to commercial laboratories to assess antimicrobial resistance patterns may result in biased estimates of prevalence of resistance. PMID- 24215610 TI - Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip. AB - A complementary cell analysis method has been developed to assess the dynamic interactions of tumor cells with resident tissue and immune cells using optical light scattering and impedance sensing to shed light on tumor cell behavior. The combination of electroanalytical and optical biosensing technologies integrated in a lab-on-a-chip allows for continuous, label-free, and noninvasive probing of dynamic cell-to-cell interactions between adherent and nonadherent cocultures, thus providing real-time insights into tumor cell responses under physiologically relevant conditions. While the study of adherent cocultures is important for the understanding and suppression of metastatic invasion, the analysis of tumor cell interactions with nonadherent immune cells plays a vital role in cancer immunotherapy research. For the first time, the direct cell-to-cell interactions of tumor cells with bead-activated primary T cells were continuously assessed using an effector cell to target a cell ratio of 10:1. PMID- 24215611 TI - Choice both affects and reflects preferences. AB - The free-choice paradigm is a widely used paradigm in psychology. It has been used to show that after a choice between two similarly pleasant stimuli, the pleasantness of the chosen one tends to increase, whereas the pleasantness of the rejected one tends to decrease-a spreading of alternatives. However, the methodological validity of the free-choice paradigm to study choice-induced preference change has recently been seriously questioned [Chen, K. M., & Risen, J. L. (2010). How choice affects and reflects preferences: Revisiting the free choice paradigm. Journal of Personality and Social Psychology, 99, 573-594. doi:10.1037/a0020217]. According to this criticism, the classically reported spreading of alternatives between the first and second rating sessions cannot be unambiguously interpreted to reflect a true change in preferences and can be observed even for completely static preferences. Here, we used two measurement sequences, a classical Rating 1-choice-Rating 2 sequence and a control Rating 1 Rating 2-choice sequence, to disentangle the spreading of alternatives driven by the effect of choice from the artefactual effect highlighted by Chen and Risen. In two studies using different stimulus material (faces and odours), we find that choice has a robust modulatory impact on preferences for rejected odours, but not for chosen odours and not for faces. PMID- 24215612 TI - Phosphine-catalyzed reactions of activated olefins tethered to cycloalkanones. substrate- and solvent-controlled synthesis of bicyclo[3.2.1]octanones, mixed acetals, and Morita-Baylis-Hillman products. AB - The n-Bu3P organocatalyzed reaction of cycloalkanones, i.e., cyclopentanones or 1,3-cyclopentanediones tethered to actived olefins, afforded selectively and in high yields three different types of products: bicyclo[3.2.1]octanones, mixed acetals, and Morita-Baylis-Hillman products. The progress of the reaction was closely related to the reaction medium and to the length of the tether located between the cyclopentanone (-dione) and the activated olefin. PMID- 24215613 TI - Surveillance of road crash injuries in Cambodia: an evaluation of the Cambodia Road Crash and Victim Information System (RCVIS). AB - OBJECTIVE: Worldwide, 1.24 million deaths and 20-50 million road crash injuries occur annually, with a disproportionate burden on low- and middle-income countries. Facing continued growth in motorized vehicles, Cambodia has begun to address road safety, including the creation of a nationwide road crash surveillance system, the Road Crash and Victim Information System (RCVIS). This study evaluates the RCVIS to understand whether road crash injuries are being monitored efficiently and effectively and to identify areas for improvement. METHODS: We used the Centers for Disease Control and Prevention's "Guidelines for Evaluating Public Health Surveillance Systems" (CDC 2001) as an evaluation framework. To assess system attributes, we conducted in-person interviews with Cambodian road safety stakeholders, including representatives from the Ministries of Health and Interior, and reviewed RCVIS annual reports and system operation documents. Characteristics assessed include usefulness, flexibility, acceptability, sensitivity, representativeness, data quality, and timeliness. RESULTS: The Cambodian government uses RCVIS data extensively for road safety planning purposes. RCVIS participation varies by type of data source, with 100 percent of police districts and 65 percent of hospitals reporting in 2010. Representativeness over time is a limitation-between 2007 and 2008, the number of reporting hospitals decreased from 65 to 42. From 2007 to 2010, the number of nonfatal injuries reported to RCVIS decreased by 35 percent, despite rapid growth in vehicle registrations. The system is timely, with annual reports disseminated within 10 months to more than 250 stakeholders. CONCLUSION: The RCVIS provides a strong foundation for the surveillance of road crash injuries and fatalities in Cambodia. Differences in participation by data source and reduced hospital participation over time affect data representativeness and may indicate issues with acceptability. Recommendations include working with hospitals to standardize reporting procedures and to increase awareness about the usefulness of the data they collect. PMID- 24215615 TI - Epigenetics and the IRFs: a complex interplay in the control of immunity and autoimmunity. AB - Effective immune responses require the coordinated activation and differentiation of several cell types, including T-cells, B-cells and myeloid cells. Abnormalities in the appropriate regulation of these processes underlie the pathogenesis of many autoimmune disorders, including systemic lupus erythematosus (SLE). Recent studies have revealed that, in addition to sequence-specific DNA binding factors, the chromatin landscape of a cell can play a pivotal role in controlling these processes and in regulating the onset of autoimmunity. Interferon regulatory factors (IRFs) are emerging as critical regulators of the activation and differentiation of immune cells and deregulation in the expression and/or function of members of the IRF family has increasingly been linked to the pathogenesis of lupus. In this review, we will provide a brief overview of the role of different IRFs in immune responses and SLE development and discuss studies, which highlight the intricate relationship of this family of transcription factors with the epigenetic machinery. PMID- 24215614 TI - The anti-erbB3 antibody MM-121/SAR256212 in combination with trastuzumab exerts potent antitumor activity against trastuzumab-resistant breast cancer cells. AB - BACKGROUND: Elevated expression of erbB3 receptor has been reported to induce resistance to therapeutic agents, including trastuzumab in erbB2-overexpressing breast cancer. Our recent studies indicate that erbB3 interacts with both erbB2 and IGF-1 receptor to form a heterotrimeric complex in trastuzumab-resistant breast cancer cells. Herein, we investigate the antitumor activity of MM 121/SAR256212, a fully human anti-erbB3 antibody (Ab), against two erbB2 overexpressing breast cancer cell lines resistant to trastuzumab. METHODS: MTS based proliferation assays were used to determine cell viability upon treatment of trastuzumab and/or MM-121/SAR256212. Cell cycle progression was examined by flow cytometric analysis. Western blot analyses were performed to determine the expression and activation of proteins. Tumor xenografts were established by inoculation of the trastuzumab-resistant BT474-HR20 cells into nude mice. The tumor-bearing mice were treated with trastuzumab and/or MM-121/SAR256212 via i.p injection to determine the Abs' antitumor activity. Immunohistochemical analyses were carried out to study the Abs' inhibitory effects on tumor cell proliferation and induction of apoptosis in vivo. RESULTS: MM-121 significantly enhanced trastuzumab-induced growth inhibition in two sensitive and two resistant breast cancer cell lines. MM-121 in combination with trastuzumab resulted in a dramatic reduction of phosphorylated erbB3 (P-erbB3) and Akt (P-Akt) in the in vitro studies. MM-121 combined with trastuzumab did not induce apoptosis in the trastuzumab-resistant cell lines under our cell culture condition, rather induced cell cycle G1 arrest mainly associated with the upregulation of p27(kip1). Interestingly, in the tumor xenograft model established from the trastuzumab resistant cells, MM-121 in combination with trastuzumab as compared to either agent alone dramatically inhibited tumor growth correlated with a significant reduction of Ki67 staining and increase of cleaved caspase-3 in the tumor tissues. CONCLUSIONS: The combination of MM-121 and trastuzumab not only inhibits erbB2-overexpressing breast cancer cell proliferation, but also promotes the otherwise trastuzumab-resistant cells undergoing apoptosis in an in vivo xenografts model. Thus, MM-121 exhibits potent antitumor activity when combined with trastuzumab under the studied conditions. Our data suggest that further studies regarding the suitability of MM-121 for treatment of breast cancer patients whose tumors overexpress erbB2 and become resistant to trastuzumab may be warranted. PMID- 24215616 TI - Iridium(III) hydrido N-heterocyclic carbene-phosphine complexes as catalysts in magnetization transfer reactions. AB - The hyperpolarization (HP) method signal amplification by reversible exchange (SABRE) uses para-hydrogen to sensitize substrate detection by NMR. The catalyst systems [Ir(H)2(IMes)(MeCN)2(R)]BF4 and [Ir(H)2(IMes)(py)2(R)]BF4 [py = pyridine; R = PCy3 or PPh3; IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene], which contain both an electron-donating N-heterocyclic carbene and a phosphine, are used here to catalyze SABRE. They react with acetonitrile and pyridine to produce [Ir(H)2(NCMe)(py)(IMes)(PPh3)]BF4 and [Ir(H)2(NCMe)(py)(IMes)(PCy3)]BF4, complexes that undergo ligand exchange on a time scale commensurate with observation of the SABRE effect, which is illustrated here by the observation of both pyridine and acetonitrile HP. In this study, the required symmetry breaking that underpins SABRE is provided for by the use of chemical inequivalence rather than the previously reported magnetic inequivalence. As a consequence, we show that the ligand sphere of the polarization transfer catalyst itself becomes hyperpolarized and hence that the high-sensitivity detection of a number of reaction intermediates is possible. These species include [Ir(H)2(NCMe)(py)(IMes)(PPh3)]BF4, [Ir(H)2(MeOH)(py)(IMes)(PPh3)]BF4, and [Ir(H)2(NCMe)(py)2(PPh3)]BF4. Studies are also described that employ the deuterium-labeled substrates CD3CN and C5D5N, and the labeled ligands P(C6D5)3 and IMes-d22, to demonstrate that dramatically improved levels of HP can be achieved as a consequence of reducing proton dilution and hence polarization wastage. By a combination of these studies with experiments in which the magnetic field experienced by the sample at the point of polarization transfer is varied, confirmation of the resonance assignments is achieved. Furthermore, when [Ir(H)2(pyridine-h5)(pyridine-d5)(IMes)(PPh3)]BF4 is examined, its hydride ligand signals are shown to become visible through para-hydrogen-induced polarization rather than SABRE. PMID- 24215617 TI - Administrative coding is specific, but not sensitive, for identifying eosinophilic esophagitis. AB - The use of administrative databases to conduct population-based studies of eosinophilic esophagitis (EoE) in the United States is limited because it is unknown whether the International Classification of Diseases, Ninth Revision (ICD 9) code for EoE, 530.13, accurately identifies those who truly have the disease. The aim of this retrospective study was to validate the ICD-9 code for identifying cases of EoE in administrative data. Confirmed cases of EoE as per consensus guidelines (symptoms of esophageal dysfunction and >=15 eosinophils per high-power field on biopsy after 8 weeks of twice daily proton pump inhibitor therapy) were identified in the University of North Carolina (UNC) EoE Clinicopathologic Database from 2008 to 2010; 2008 was the first year in which the 530.13 code was approved. Using the Carolina Data Warehouse, the administrative database for patients seen in the UNC system, all diagnostic and procedure codes were obtained for these cases. Then, with the EoE cases as the reference standard, we re-queried the Carolina Data Warehouse over the same time frame for all patients seen in the system (n=308,372) and calculated the sensitivity and specificity of the ICD-9 code 530.13 as a case definition of EoE. To attempt to refine the case definition, we added procedural codes in an iterative fashion to optimize sensitivity and specificity, and restricted our analysis to privately insured patients. We also conducted a sensitivity analysis with 2011 data to identify trends in the operating parameters of the code. We identified 226 cases of EoE at UNC to serve as the reference standard. The ICD-9 code 530.13 yielded a sensitivity of 37% (83/226; 95% confidence interval: 31 43%) and specificity of 99% (308,111/308,146; 95% confidence interval: 98-100%). These operating parameters were not substantially altered if the case definition required a procedure code for endoscopy or if cases were limited to those with commercial insurance. However, in 2011, the sensitivity of the code had increased to 61%, while the specificity remained at 99%. The ICD-9 code for EoE, 530.13, had excellent specificity for identifying cases of EoE in administrative data, although this high specificity was achieved at an academic center. Additionally, the sensitivity of the code appears to be increasing over time, and the threshold at which it will stabilize is not known. While use of this administrative code will still miss a number of cases, those identified in this manner are highly likely to have the disease. PMID- 24215619 TI - Early dynamic PET/CT shows open portocaval shunt in a patient with liver cirrhosis. PMID- 24215618 TI - Importance of high-density lipoprotein cholesterol levels in elderly diabetic individuals with type IIb dyslipidemia: A 2-year survey of cardiovascular events. AB - AIM: The risk factors for ischemic heart disease (IHD) or cerebrovascular accident (CVA) in elderly diabetic individuals with type IIb dyslipidemia are not fully known. Therefore, we investigated the relationship between lipid levels and IHD and CVA in diabetic individuals with type IIb dyslipidemia. METHOD: The Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4014 type 2 diabetic patients (1936 women; age 67.4 +/- 9.5 years). The primary end points were the onset of IHD or CVA. Lipid and glucose levels, and other factors were investigated in relation to the occurrence of IHD or CVA. A total of 462 participants were included in the group of patients with type IIb dyslipidemia. RESULTS: The 462 diabetic participants with type IIb dyslipidemia were divided into those who were aged <65 years, 65-74 years and >75 years (n=168, 190 and 104, respectively). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol/HDL-C were significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years, and HDL-C and diastolic blood pressure was significantly associated with cardiovascular events in patients aged 65-74 years. Non-HDL-C was not significantly associated with the risk of cardiovascular events. Multiple regression analysis showed that lower HDL-C was significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years and 65-74 years. CONCLUSIONS: Lower HDL-C was an important risk factor for cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <75 years. PMID- 24215620 TI - Poor responses to tyrosine kinase inhibitors in a child with precursor B-cell acute lymphoblastic leukemia with SNX2-ABL1 chimeric transcript. AB - In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2-ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2-ABL1 fusion exhibited a BCR-ABL1+ ALL-like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype-based treatment stratification for patients with SNX2-ABL1 fusion. PMID- 24215621 TI - Base-mediated chemo- and stereoselective addition of 5-aminoindole/tryptamine and histamines onto alkynes. AB - Transition-metal-free chemo- and stereoselective addition of 5-aminoindole (1a), tryptamine (1b), and histamine (1c) to alkynes 2a-s to synthesize the indolyl/imidazolyl enamines 3a-p, 5a-o, and 6a-e using superbasic solutions of alkali-metal hydroxides in DMSO is described. The addition of N-heterocycles onto alkynes takes places chemoselectively without affecting the 1 degrees amino groups (aromatic and aliphatic) of 5-aminoindole, tryptamine, and histamine. The stereochemistry of the products was found to be dependent upon reaction time; an increase in reaction time leads to the formation of a mixture of E/Z isomers and the thermodynamically stable E addition product. The chemoselective addition of N heterocycle 1a onto alkyne over thiophenol 7 and phenol 8 is supported by control experiments. Competitive experiments showed that 5-aminoindole was more reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient chemoselective method to synthesize a variety of (Z)-enamines of 5-aminoindole, tryptamine, and histamine without affecting the 1 degrees amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which proved to be highly advantageous for structural and biological activity assessments. PMID- 24215623 TI - Assessment of tear meniscus with optical coherence tomography in thyroid associated ophtalmopathy. AB - PURPOSE: To evaluate the tear-film meniscus with optical coherence tomography (OCT) in patients with Graves' disease (GD). MATERIALS AND METHODS: Patients with GD without clinical features of thyroid-associated ophthalmopathy (TAO) (Group 1, n=35), patients with signs of TAO (Group 2, n=31) and healthy participants (Group 3, n=31) were enrolled. Palpebral fissure width, Schirmer test, tear break-up time (TBUT) test and tear-film meniscus height and area obtained with Fourier domain-OCT were analyzed. RESULTS: TBUT test scores were 8 s (2-25) in Group 1, 8 s (2-15) in Group 2 (p=0.380); and 10 s (5-17) in Group 3 (p=0.000 Group 1 versus 3, and 0.000 for Group 2 versus 3). Tear-film meniscus height did not significantly differ between Groups 1 and 2 (257.5 um (86-962) and 258 um (99 1340), respectively, p=0.980). In Group 3, tear-film meniscus height was 316 um (122-720) (p=0.005 Group 1 versus 3 and 0.004 for Group 2 versus 3). Tear-film meniscus area did not significantly differ between Groups 1 and 2 (0.025 mm(2) (0.004-0.250) and 0.024 mm(2) (0.003-0.316), respectively, p=0.850). In Group 3, tear-film meniscus area was 0.048 mm(2) (0.006-0.75) (p=0.000 Group 1 versus 3 and 0.000 for Group 2 versus 3). CONCLUSION: Tear function is significantly disturbed in GD. OCT is an effective way to assess the tearing function also in patients with GD. PMID- 24215622 TI - Fusion of the C-terminal triskaidecapeptide of hirudin variant 3 to alpha1 proteinase inhibitor M358R increases the serpin-mediated rate of thrombin inhibition. AB - BACKGROUND: Alpha-1 proteinase inhibitor (API) is a plasma serpin superfamily member that inhibits neutrophil elastase; variant API M358R inhibits thrombin and activated protein C (APC). Fusing residues 1-75 of another serpin, heparin cofactor II (HCII), to API M358R (in HAPI M358R) was previously shown to accelerate thrombin inhibition over API M358R by conferring thrombin exosite 1 binding properties. We hypothesized that replacing HCII 1-75 region with the 13 C terminal residues (triskaidecapeptide) of hirudin variant 3 (HV354-66) would further enhance the inhibitory potency of API M358R fusion proteins. We therefore expressed HV3API M358R (HV354-66 fused to API M358R) and HV3API RCL5 (HV354-66 fused to API F352A/L353V/E354V/A355I/I356A/I460L/M358R) API M358R) as N terminally hexahistidine-tagged polypeptides in E. coli. RESULTS: HV3API M358R inhibited thrombin 3.3-fold more rapidly than API M358R; for HV3API RCL5 the rate enhancement was 1.9-fold versus API RCL5; neither protein inhibited thrombin as rapidly as HAPI M358R. While the thrombin/Activated Protein C rate constant ratio was 77-fold higher for HV3API RCL5 than for HV3API M358R, most of the increased specificity derived from the API F352A/L353V/E354V/A355I/I356A/I460L API RCL 5 mutations, since API RCL5 remained 3-fold more specific than HV3API RCL5. An HV3 54-66 peptide doubled the Thrombin Clotting Time (TCT) and halved the binding of thrombin to immobilized HCII 1-75 at lower concentrations than free HCII 1-75. HV3API RCL5 bound active site-inhibited FPR-chloromethyl ketone-thrombin more effectively than HAPI RCL5. Transferring the position of the fused HV3 triskaidecapeptide to the C-terminus of API M358R decreased the rate of thrombin inhibition relative to that mediated by HV3API M358R by 11-to 14-fold. CONCLUSIONS: Fusing the C-terminal triskaidecapeptide of HV3 to API M358R containing serpins significantly increased their effectiveness as thrombin inhibitors, but the enhancement was less than that seen in HCII 1-75-API M358R fusion proteins. HCII 1-75 was a superior fusion partner, in spite of the greater affinity of the HV3 triskaidecapeptide, manifested both in isolated and API-fused form, for thrombin exosite 1. Our results suggest that HCII 1-75 binds thrombin exosite 1 and orients the attached serpin scaffold for more efficient interaction with the active site of thrombin than the HV3 triskaidecapeptide. PMID- 24215624 TI - Assessment of bone health in preterm infants through quantitative ultrasound and biochemical markers. AB - OBJECTIVE: To assess bone status in preterm infants with quantitative ultrasound and to search for biochemical markers of bone health. METHODS: Metacarpus bone transmission time (mcBTT) was prospectively performed during hospitalization, together with biochemical and clinical outcomes analysis. RESULTS: 154 patients were studied. At 3rd week of life mcBTT positively correlated with serum phosphate. Urinary excretion of calcium and phosphate were assessed in a subgroup of 55 patients: on day 21 mcBTT positively correlated with phosphaturia, negatively with calciuria. Gestational age (GA), weight and length at 3rd week and at 36 weeks of GA correlated positively with mcBTT. We found negative correlation between mcBTT at 3rd week and days of parenteral nutrition, mechanical ventilation period and days to reach 1800 g. CONCLUSIONS: Serum phosphate, phosphaturia and calciuria correlate most with mcBTT. Further studies are necessary to verify the possible influence of early bone status on future bone health. PMID- 24215625 TI - Adult self-reported and objectively monitored physical activity and sedentary behavior: NHANES 2005-2006. AB - BACKGROUND: It remains unclear what people are attempting to communicate, in terms of objectively monitored behavior, when describing their physical activity and sedentary behavior through self-report. The purpose of this study was to examine various objectively monitored accelerometer variables (e.g., moderate-to vigorous physical activity [MVPA], steps/day, sedentary time, etc.) across categories of self-reported MVPA (< 150 vs. >= 150 minutes/week), usual occupational/domestic activity (UODA; "mostly sitting" vs. "stand, walk, lift, or carry"), and leisure-time sedentary behavior (LTSB; >= 3 vs. < 3 hours/day) in a nationally representative sample of U.S. adults (>= 20 years). METHODS: This is a secondary analysis of 3,725 participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) who provided relevant questionnaire responses and >= 1 day of valid accelerometer data. Descriptive statistics were computed for various objectively monitored accelerometer variables across categories of self-reported MVPA, UODA, and LTSB. Pairwise comparisons were conducted to examine differences in objectively monitored behavior between categories of self-reported MVPA, UODA, and LTSB. RESULTS: On average, adults reporting compliance with physical activity guidelines (>= 150 minutes/week of MVPA) accumulated more objectively measured physical activity and similar amounts of sedentary time relative to those reporting not achieving guidelines. Adults reporting their daily UODA as "mostly sitting" or accruing >= 3 hours/day of LTSB accumulated less objectively monitored physical activity and more sedentary time than those who described their UODA as "stand, walk, lift, or carry" or accrued < 3 hours/day of LTSB. The most active cross-classified category (7,935 steps/day; >= 150 minutes/week of self-reported MVPA, "stand, walk, lift, or carry" UODA, and < 3 hours/day of LTSB) accumulated more than twice as many daily steps as the least active cross-classified category (3,532 steps/day; < 150 minutes/week of self-reported MVPA, "mostly sitting" UODA, and >= 3 hours/day of LTSB). CONCLUSIONS: A number of objectively monitored physical activity indicators varied significantly between self-reported MVPA, UODA, and LTSB categories, while objectively monitored sedentary time only varied between UODA and LTSB categories. Cross-classifications of self-reported MVPA, UODA, and LTSB responses depict a greater range of physical activity than viewing dichotomous responses for these variables one-at-a-time. PMID- 24215626 TI - Growth of infants fed formula supplemented with Bifidobacterium lactis Bb12 or Lactobacillus GG: a systematic review of randomized controlled trials. AB - BACKGROUND: Growth is an essential outcome measure for evaluating the safety of any new ingredients, including probiotics, added to infant formulae. The aim of this systematic review was to determine the effects of supplementation of infant formulae with Bifidobacterium lactis Bb12 (B lactis) and/or Lactobacillus rhamnosus GG (LGG) compared with unsupplemented formula on the growth of healthy infants. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2013 for relevant randomized controlled trials (RCTs) conducted in healthy term infants. Unpublished data were obtained from the manufacturer of B lactis-supplemented formula. The primary outcome measures were weight, length, and head circumference. RESULTS: Nine eligible trials were identified. Compared with unsupplemented controls, supplementation of infant formula with B lactis had no effect on weight gain [4 RCTs, n = 266, mean difference (MD) 0.96 g/day, 95% confidence interval (CI) -0.70 to 2.63)], length gain (4 RCTs, n = 261, MD -0.39 mm/month, 95% CI -1.32 to 0.53), or head circumference gain (3 RCTs, n = 207, MD 0.56 mm/month, 95% CI -0.17 to 1.30). Data limited to one small (n = 105) trial suggest that infants who received standard infant formula supplemented with LGG grew significantly better. No such effect was observed in infants fed hydrolyzed formula supplemented with LGG. CONCLUSIONS: Supplementation of infant formula with B lactis results in growth similar to what is found in infants fed unsupplemented formula. Limited data do not allow one to reach a conclusion regarding the effect of LGG supplementation on infant growth. PMID- 24215627 TI - Ab initio modeling of excitonic and charge-transfer states in organic semiconductors: the PTB1/PCBM low band gap system. AB - A detailed quantum chemical simulation of the excitonic and charge-transfer (CT) states of a bulk heterojunction model containing poly(thieno[3,4-b]thiophene benzodithiophene) (PTB1)/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) is reported. The largest molecular model contains two stacked PTB1 trimer chains interacting with C60 positioned on top of and lateral to the (PTB1)3 stack. The calculations were performed using the algebraic diagrammatic construction method to second order (ADC(2)). One main result of the calculations is that the CT states are located below the bright inter-chain excitonic state, directly accessible via internal conversion processes. The other important aspects of the calculations are the formation of discrete bands of CT states originating from the lateral C60's and the importance of inter-chain charge delocalization for the stability of the CT states. A simple model for the charge separation step is also given, revealing the energetic feasibility of the overall photovoltaic process. PMID- 24215628 TI - Doxorubicin -eluting beads in the treatment of liver carcinoma. AB - INTRODUCTION: Doxorubicin and especially doxorubicin-eluting beads (DEBs) have become an intensive study subject in the locoregional therapy of liver carcinoma over the past 6 years. Since sorafenib has become the new standard in the treatment of advanced liver carcinoma and has been combined with DEB in clinical studies to evaluate safety and efficacy, it has shown promising results. Thus, the authors have investigated the evidence that DEB is a potential drug in the treatment of intermediate liver carcinoma, even in combination with systemic therapies. AREAS COVERED: Evaluation of published articles in English using metadatabase such as PubMed. EXPERT OPINION: Since there is no standard therapy regimen in the locoregional transarterial treatment of intermediate liver carcinoma, DEBs were designed to offer an attempt to homogenize the use of cytostatic and embolic agents. The development of so-called doxorubicin-eluting beads in the past few years is an effort to minimize systemic toxicity and increase local drug concentration. In the therapy of liver carcinoma, doxorubicin should not be systemically administered due to its high toxicity. Clinical trials indicate that the administration of DEB is safe and effective for the treatment of liver carcinoma and can even be combined with systemic drugs such as sorafenib. PMID- 24215629 TI - 1-Azadienes as regio- and chemoselective dienophiles in aminocatalytic asymmetric Diels-Alder reaction. AB - Electron-deficient 1-aza-1,3-butadienes containing a 1,2-benzoisothiazole-1,1 dioxide or 1,2,3-benzoxathiazine-2,2-dioxide motif act as regio- and chemoselective dienophiles in normal-electron-demand Diels-Alder reactions with HOMO-raised trienamines, rather than typical 4pi-participation in inverse electron-demand versions. The enantioenriched cycloadducts could be efficiently converted to spiro or fused frameworks with high structural and stereogenic complexity by a sequential aza-benzoin reaction or other transformations. PMID- 24215630 TI - High-strength nanocellulose-talc hybrid barrier films. AB - Hybrid organic-inorganic films mimicking natural nacre-like composite structures were fabricated from cellulose nanofibers obtained from sequential periodate chlorite oxidation treatment and talc platelets, using a simple vacuum-filtration method. As a pretreatment, commercial talc aggregates were individualized into well-dispersed talc platelets using a wet stirred media mill with high-shear conditions to promote the homogeneity and mechanical characteristics of hybrids. The nanofiber-talc hybrids, which had talc contents from 1 to 50 wt %, were all flexible in bending, and possessed tensile strength and Young's modulus values up to 211 +/- 3 MPa and 12 +/- 1 GPa, respectively, the values being remarkably higher than those reported previously for nanofibrillated cellulose-talc films. Because of the lamellar and well-organized structure of hybrids in which the talc platelets were evenly embedded, they possessed a small pore size and good oxygen barrier properties, as indicated by the preliminary results. The talc platelets decreased the moisture adsorption of highly talc-loaded hybrids, although they still exhibited hydrophilic surface characteristics in terms of contact angles. PMID- 24215631 TI - Changing rates for liver and lung cancers in Qidong, China. AB - Residents of Qidong, China are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic, and environmental factors. This Perspective On Statistical Trends examines the China age-standardized incidence rates (CASR), as tracked by the Qidong Cancer Registry for the past 40 years, for the two leading cancer killers in Qidong, liver and lung. Both cancer types are strongly influenced by environmental factors. The CASR for liver cancer has dropped nearly 50% in the last 4 decades, in part from access to deep-well drinking water in the 1970s with consequent diminished exposure to tumor promoting microcystins produced by blue green algae. There have also been substantive reductions in exposures to dietary aflatoxins, as economic reform in the mid-1980s fostered a wholesale change in dietary staple from maize to rice. In men, lung cancer CASR has trebled over this period, likely driven by a high prevalence of smokers (~65%) and an ever increasing smoking frequency in this population. Qidong women, by contrast, rarely smoke and have exhibited a flat CASR until the past decade where lung cancer rates have now doubled. This upturn may reflect an increasing burden of indoor and outdoor air pollution. PMID- 24215633 TI - Modeling the frequency of opposing left-turn conflicts at signalized intersections using generalized linear regression models. AB - OBJECTIVE: The primary objective of this study was to identify whether the frequency of traffic conflicts at signalized intersections can be modeled. The opposing left-turn conflicts were selected for the development of conflict predictive models. METHODS: Using data collected at 30 approaches at 20 signalized intersections, the underlying distributions of the conflicts under different traffic conditions were examined. Different conflict-predictive models were developed to relate the frequency of opposing left-turn conflicts to various explanatory variables. The models considered include a linear regression model, a negative binomial model, and separate models developed for four traffic scenarios. The prediction performance of different models was compared. RESULTS: The frequency of traffic conflicts follows a negative binominal distribution. The linear regression model is not appropriate for the conflict frequency data. In addition, drivers behaved differently under different traffic conditions. Accordingly, the effects of conflicting traffic volumes on conflict frequency vary across different traffic conditions. CONCLUSIONS: The occurrences of traffic conflicts at signalized intersections can be modeled using generalized linear regression models. The use of conflict predictive models has potential to expand the uses of surrogate safety measures in safety estimation and evaluation. PMID- 24215632 TI - 6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2alpha. AB - BACKGROUND: 6-Shogaol is a promising antitumor agent isolated from dietary ginger (Zingiber officinale). However, little is known about the efficacy of 6-shogaol on leukemia cells. Here we investigated the underlying mechanism of 6-shogaol induced apoptosis in human leukemia cells in vitro and in vivo. METHODS: Three leukemia cell lines and primary leukemia cells were used to investigate the apoptosis effect of 6-shogaol. A shotgun approach based on label-free proteome with LC-CHIP Q-TOF MS/MS was employed to identify the cellular targets of 6 shogaol and the differentially expressed proteins were analyzed by bioinformatics protocols. RESULTS: The present study indicated that 6-shogaol selectively induced apoptosis in transformed and primary leukemia cells but not in normal cells. Eukaryotic translation initiation factor 2 alpha (eIF2alpha), a key regulator in apoptosis signaling pathway, was significantly affected in both Jurkat and U937 proteome profiles. The docking results suggested that 6-shogaol might bind well to eIF2alpha at Ser51 of the N-terminal domain. Immunoblotting data indicated that 6-shogaol induced apoptosis through a process involving dephosphorylation of eIF2alpha and caspase activation-dependent cleavage of eIF2alpha. Furthermore, 6-shogaol markedly inhibited tumor growth and induced apoptosis in U937 xenograft mouse model. CONCLUSION: The potent anti-leukemia activity of 6-shogaol found both in vitro and in vivo in our study make this compound a potential anti-tumor agent for hematologic malignancies. PMID- 24215634 TI - Using sodium molybdate to treat chronic copper toxicity in dairy cows: A practical approach. AB - Abstract CASE HISTORY: A Jersey herd of 350 cows and 70 heifers located in the Taranaki region of New Zealand ceased milking in June 2011. Ten cows died during the subsequent 14 days. For at least 9 months, the cows had received palm kernel expeller (PKE) and molasses supplements. Additional Cu supplementation was provided through the water system. Total Cu intake was calculated to be 400 mg/day/cow. CLINICAL AND PATHOLOGICAL FINDINGS: Half of the cows died suddenly while others presented with anorexia, depression and ataxia, which progressed to recumbency and death after 1 to 3 days. Clinical signs were mild dehydration, cyanosis and firm faeces which were covered in dark blood. Mean concentrations of Cu in liver and kidney in three of the dead cows were 3,900 and 440 umol/kg fresh weight (FW), respectively. Haemorrhages were observed throughout the alimentary tracts and in muscles, and there were ecchymotic haemorrhages on the epi- and endocardia. The livers were swollen and the gall bladder walls were inflamed. DIAGNOSIS: High concentrations of Cu in the liver and kidney are characteristic findings of chronic Cu toxicity. TREATMENT: The remaining herd was fed 200 mg Mo, as sodium molybdate, per cow per day and all Cu supplements were removed including those provided by the water supply. This reduced mean concentrations of Cu in liver from 3,100 to 1,320 umol/kg FW within 26 days in the five live animals that were biopsied. There were no further deaths. CLINICAL RELEVANCE: In dairy herds where excessive Cu intakes have resulted in high liver Cu concentrations and caused chronic Cu toxicity, the removal of all Cu supplements and provision of high intakes of Mo (200 mg/cow/day) can markedly reduce liver Cu stores within 4 weeks. PMID- 24215635 TI - The protective effect of thiamine pyrophosphate, but not thiamine, against cardiotoxicity induced with cisplatin in rats. AB - This study investigated the effect of thiamine pyrophosphate on oxidative damage associated with cardiotoxicity caused by cisplatin (CIS), an antineoplastic agent, in rats, and compared this with thiamine. Animals used in the study were divided into four groups of 6 rats each. These represented a control group receiving 5 mg/kg of CIS, study groups receiving 20 mg/kg of thiamine pyrophosphate plus 5 mg/kg of cisplatin (CTPG) or 20 mg/kg of thiamine plus 5 mg/kg of cisplatin and a healthy (H) group. All doses were administered intraperitoneally once a day for 14 days. Malondialdehyde, total glutathione and products of DNA injury results were similar in the CTPG and H groups (p > 0.05). Creatinine kinase, creatine kinase MB and troponin 1 levels were similar in the CTPG and H groups (p > 0.05). Thiamine pyrophosphate prevented CIS-associated oxidative stress and heart injury, whereas thiamine did not prevent these. PMID- 24215636 TI - DNA quantification via ICP-MS using lanthanide-labeled probes and ligation mediated amplification. AB - The combination of lanthanide-tagged oligonucleotide probes with inductively coupled plasma mass spectrometry (ICP-MS) as the detection technique is a novel labeling and analysis strategy for heterogeneous nucleic acid quantification assays. We describe a hybridization assay based on biotin-streptavidin affinity using lanthanide-labeled reporter probes and biotinylated capture probes. For the basic sandwich type assay, performed in streptavidin-coated microtitration wells, the limit of detection (LOD) was 7.2 fmol of DNA target, corresponding to a final concentration of 6 pM terbium-labeled probes detectable by ICP-MS after elution from the solid support. To improve the sensitivity and sequence specificity of the approach, it was combined with established molecular biological techniques, i.e., elution with a restriction endonuclease and signal and target amplification by the ligase detection reaction (LDR) and ligase chain reaction (LCR), respectively. Initial experiments showed that the enzymes facilitated the discrimination of single-base mismatches within the recognition or ligation site. Furthermore, LCR as a target amplification step resulted in a 6000-fold increase of sensitivity, and finally an LOD of 2.6 amol was achieved with an artificial double-stranded DNA target. PMID- 24215637 TI - BioTechniques: Celebrating 30 years of methods development. PMID- 24215638 TI - Establishing isogenic inducible cell lines using founder reporter lines and recombinase-mediated cassette exchange. AB - Manipulating gene expression in mammalian cell lines is one of the most widely used methods for studying gene function. Tetracycline- and doxycycline-inducible systems are sensitive, reproducible, relatively inexpensive, and proven to work well in both cell lines and mouse models. However, obtaining homogeneous transgene expression or uniform knockdown by short hairpin RNA requires time consuming and labor-intensive single-cell cloning to derive stable cell lines. For this reason, Tet-inducible cell systems have yet to be widely adopted. Here we describe the XT-cell method, a novel system for establishing isogenic inducible cell lines using founder reporter lines and recombinase-mediated cassette exchange. We demonstrate that, using this XT-cell method, isogenic stable Tet-inducible cell lines can be efficiently created with much less effort and time as compared with conventional methods. The XT-plasmids and the XT founder cell lines will be a valuable resource to researchers interested in versatile modulation of gene expression in cell culture systems, and this method has the potential to expedite many aspects of biomedical research. PMID- 24215639 TI - Correlative light microscopy for high-content screening. AB - High-throughput microscopy is an effective tool for rapidly collecting data on a large scale. However, high throughput comes at the cost of low spatial resolution. Here we introduce correlative light microscopy by combining fast automated widefield imaging, confocal microscopy and super-resolution microscopy. We demonstrate the potential of this approach for scalable experiments. The workflow consists of a robust approach for selecting cells of interest on a wide field screening microscope at low resolution and subsequently re-localizing those cells with micrometer precision for confocal and super-resolution imaging. As a case study, we visualized and quantified cis- and trans-Golgi markers at increasing resolution. PMID- 24215640 TI - Microsatellite marker discovery using single molecule real-time circular consensus sequencing on the Pacific Biosciences RS. AB - Microsatellite sequences are important markers for population genetics studies. In the past, the development of adequate microsatellite primers has been cumbersome. However with the advent of next-generation sequencing technologies, marker identification in genomes of non-model species has been greatly simplified. Here we describe microsatellite discovery on a Pacific Biosciences single molecule real-time sequencer. For the Greater White-fronted Goose (Anser albifrons), we identified 316 microsatellite loci in a single genome shotgun sequencing experiment. We found that the capability of handling large insert sizes and high quality circular consensus sequences provides an advantage over short read technologies for primer design. Combined with a straightforward amplification-free library preparation, PacBio sequencing is an economically viable alternative for microsatellite discovery and subsequent PCR primer design. PMID- 24215641 TI - New vectors for epitope tagging and gene disruption in Schizosaccharomyces pombe. AB - We describe a series of new vectors for PCR-based epitope tagging and gene disruption in the fission yeast Schizosaccharomyces pombe, an exceptional model organism for the study of cellular processes. The vectors are designed for amplification of gene-targeting DNA cassettes and integration into specific genetic loci, allowing expression of proteins fused to 12 tandem copies of the Pk (V5) epitope or 5 tandem copies of the FLAG epitope with a glycine linker. These vectors are available with various antibiotic or nutritional markers and are useful for protein studies using biochemical and cell biological methods. We also describe new vectors for fluorescent protein-tagging and gene disruption using ura4MX6, LEU2MX6, and his3MX6 selection markers, allowing researchers in the S. pombe community to disrupt genes and manipulate genomic loci using primer sets already available for the widely used pFA6a-MX6 system. Our new vectors may also be useful for gene manipulation in Saccharomyces cerevisiae. PMID- 24215642 TI - Single step BP/LR combined Gateway reactions. AB - The Gateway recombination system is characterized by its ability to transfer DNA sequences back and forth between an intermediate clone (the entry clone) and a variety of destination vectors. However, a number of applications do not need to exploit the advantages offered by the entry clone. Here we report reaction conditions for cloning DNA fragments into destination vectors in a single step reaction, thus reducing the cost and overall time needed to obtain an expression clone from three days to one. PMID- 24215643 TI - Terminator oligo blocking efficiently eliminates rRNA from Drosophila small RNA sequencing libraries. AB - A large number of methods are available to deplete ribosomal RNA reads from high throughput RNA sequencing experiments. Such methods are critical for sequencing Drosophila small RNAs between 20 and 30 nucleotides because size selection is not typically sufficient to exclude the highly abundant class of 30 nucleotide 2S rRNA. Here we demonstrate that pre-annealing terminator oligos complimentary to Drosophila 2S rRNA prior to 5' adapter ligation and reverse transcription efficiently depletes 2S rRNA sequences from the sequencing reaction in a simple and inexpensive way. This depletion is highly specific and is achieved with minimal perturbation of miRNA and piRNA profiles. PMID- 24215644 TI - Survivors of brain injury through the eyes of the public: a systematic review. AB - BACKGROUND: It is known that knowledge and attitudes are important in determining whether society stigmatize and discriminate against specific groups. However, there has been no systematic review of the literature measuring these factors towards acquired brain injury (ABI). OBJECTIVE: This study aimed to systematically evaluate the literature measuring the public's (1) knowledge of ABI and (2) attitudes towards survivors. METHODS: Four databases were searched between December 2011 and March 2012. Studies meeting the selection criteria were included and a manual search of studies' reference lists undertaken to identify any remaining. The quality of studies was assessed using an adapted tool. RESULTS: Twenty studies were reviewed, with quality assessment ratings ranging from 47.83-91.3%. The public lacked awareness of some post-injury symptoms. Misconceptions concerning recovery, memory difficulties and vulnerability to second injuries were also commonly endorsed. The public demonstrated more negative attitudes towards survivors of ABI than those with other injuries, particularly if they deemed the individual responsible for their ABI. CONCLUSIONS: Survivors of ABI are vulnerable to stigma and discrimination. It is therefore essential that Government and media campaigns prioritize educating the public about ABI and promote the inclusion of survivors. PMID- 24215645 TI - SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region. AB - BACKGROUND: Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. RESULTS: We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. CONCLUSIONS: We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to the immunoprotective mechanism of fish DNA vaccine. PMID- 24215646 TI - Digermylene oxide complexes: facile synthesis and reactivity. AB - A simple heating of aminotroponiminate (ATI) ligand stabilized germylene monochlorides [(R)2ATIGeCl] (R = t-Bu 1, i-Bu 2) with an excess of potassium hydroxide in toluene resulted in the first ATI ligand stabilized digermylene oxides [{(R)2ATIGe}2O] (R = t-Bu 3, i-Bu 4), respectively. Reaction of compound 3 with elemental sulfur and selenium gave the first germaacid anhydride complexes [{(t-Bu)2ATIGe(E)}2O] (E = S 5, Se 6) with (S)Ge-O-Ge(S) and (Se)Ge-O-Ge(Se) moieties, respectively. The digermylene oxide complexes 3 and 4 and germaacid anhydride complexes 5 and 6 were characterized by multinuclear NMR spectroscopy and single-crystal X-ray diffraction analysis. In its (77)Se NMR spectrum, compound 6 showed a resonance at -78.9 ppm. The Ge-O-Ge bond angles in compounds 5 and 6 are 178.66(2) degrees and 179.81(2) degrees , respectively. To understand further the bonding features, DFT calculations followed by MO, AIM, and NBO analysis were carried out on compounds 3, 5, and 6. The computed Wiberg bond indices of Ge-O bonds are slightly less than 0.5 in all the aforementioned compounds, and the same for the Ge?E bonds in compounds 5 and 6 are close to 1.4. PMID- 24215647 TI - Beyond intensity: Spectral features effectively predict music-induced subjective arousal. AB - Emotions in music are conveyed by a variety of acoustic cues. Notably, the positive association between sound intensity and arousal has particular biological relevance. However, although amplitude normalization is a common procedure used to control for intensity in music psychology research, direct comparisons between emotional ratings of original and amplitude-normalized musical excerpts are lacking. In this study, 30 nonmusicians retrospectively rated the subjective arousal and pleasantness induced by 84 six-second classical music excerpts, and an additional 30 nonmusicians rated the same excerpts normalized for amplitude. Following the cue-redundancy and Brunswik lens models of acoustic communication, we hypothesized that arousal and pleasantness ratings would be similar for both versions of the excerpts, and that arousal could be predicted effectively by other acoustic cues besides intensity. Although the difference in mean arousal and pleasantness ratings between original and amplitude-normalized excerpts correlated significantly with the amplitude adjustment, ratings for both sets of excerpts were highly correlated and shared a similar range of values, thus validating the use of amplitude normalization in music emotion research. Two acoustic parameters, spectral flux and spectral entropy, accounted for 65% of the variance in arousal ratings for both sets, indicating that spectral features can effectively predict arousal. Additionally, we confirmed that amplitude-normalized excerpts were adequately matched for loudness. Overall, the results corroborate our hypotheses and support the cue redundancy and Brunswik lens models. PMID- 24215648 TI - Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors. AB - INTRODUCTION: We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF). METHODS: This is an observational cohort study using data prospectively collected over a three year period in a medical ICU of a university hospital. RESULTS: Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO2/FiO2 >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation. CONCLUSIONS: With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO2/FiO2 > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality. PMID- 24215649 TI - Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care. AB - AIM: To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. METHODS: In total, 179 participants aged >= 65 years who were eligible for long-term care insurance (mean age 85.5 +/- 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. RESULTS: For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (P<0.001). The indirect effect of nutritional status through physical function on the activities of daily living was 0.458 (P<0.001). Finally, no significant direct effect of nutritional status on activities of daily living was observed (b=0.058, P=0.258). CONCLUSIONS: The present study identified the complex pathway from nutritional status to the activities of daily living through physical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. PMID- 24215650 TI - Fast automated yeast cell counting algorithm using bright-field and fluorescence microscopic images. AB - BACKGROUND: The faithful determination of the concentration and viability of yeast cells is important for biological research as well as industry. To this end, it is important to develop an automated cell counting algorithm that can provide not only fast but also accurate and precise measurement of yeast cells. RESULTS: With the proposed method, we measured the precision of yeast cell measurements by using 0%, 25%, 50%, 75% and 100% viability samples. As a result, the actual viability measured with the proposed yeast cell counting algorithm is significantly correlated to the theoretical viability (R2 = 0.9991). Furthermore, we evaluated the performance of our algorithm in various computing platforms. The results showed that the proposed algorithm could be feasible to use with low-end computing platforms without loss of its performance. CONCLUSIONS: Our yeast cell counting algorithm can rapidly provide the total number and the viability of yeast cells with exceptional accuracy and precision. Therefore, we believe that our method can become beneficial for a wide variety of academic field and industries such as biotechnology, pharmaceutical and alcohol production. PMID- 24215651 TI - Comparative genomics analysis of Streptococcus agalactiae reveals that isolates from cultured tilapia in China are closely related to the human strain A909. AB - BACKGROUND: Streptococcus agalactiae, also referred to as Group B Streptococcus (GBS), is a frequent resident of the rectovaginal tract in humans, and a major cause of neonatal infection. In addition, S. agalactiae is a known fish pathogen, which compromises food safety and represents a zoonotic hazard. The complete genome sequence of the piscine S. agalactiae isolate GD201008-001 was compared with 14 other piscine, human and bovine strains to explore their virulence determinants, evolutionary relationships and the genetic basis of host tropism in S. agalactiae. RESULTS: The pan-genome of S. agalactiae is open and its size increases with the addition of newly sequenced genomes. The core genes shared by all isolates account for 50 ~ 70% of any single genome. The Chinese piscine isolates GD201008-001 and ZQ0910 are phylogenetically distinct from the Latin American piscine isolates SA20-06 and STIR-CD-17, but are closely related to the human strain A909, in the context of the clustered regularly interspaced short palindromic repeats (CRISPRs), prophage, virulence-associated genes and phylogenetic relationships. We identified a unique 10 kb gene locus in Chinese piscine strains. CONCLUSIONS: Isolates from cultured tilapia in China have a close genomic relationship with the human strain A909. Our findings provide insight into the pathogenesis and host-associated genome content of piscine S. agalactiae isolated in China. PMID- 24215652 TI - Straight video blades are advantageous than curved blades in simulated pediatric difficult intubation. AB - BACKGROUND: It is still controversial which laryngoscope may be a better option in unanticipated difficult airway in pediatric patients. The aim of the present study was to compare two direct and two video-assisted laryngoscope devices for the management of difficult pediatric airway. METHODS: Forty-five anesthesiology residents and nurse anesthetists participated in the study. Macintosh, Miller, Storz Miller, and McGrath Mac curved laryngoscopes were used for tracheal intubation of 3-6-month Airsim Pierre Robin manikin. We compared the duration of successful intubation, number of attempts, glottic view grades, severity of dental trauma, the use of optimization maneuvers, and the difficulty of use of the devices with straight and curved laryngoscope blades. RESULTS: Successful intubation duration was significantly lower in Storz Miller device, and the number of intubation attempts was significantly higher in the Macintosh laryngoscope (P < 0.01). According to the Cormack and Lehane classification, Grades 1 and 2 glottic view was 20% for Macintosh and 40% for Miller laryngoscope, while it was 100% for Storz Miller and 80% for McGrath (P < 0.001). Difficulty VAS scores of Storz Miller device were significantly lower than the scores of Macintosh, Miller, and McGrath laryngoscopes (15.7 +/- 14.89, 34.7 +/- 26.44, 31.5 +/- 26.74, 33.4 +/- 26.67 mm, respectively; P < 0.01). The severity of dental trauma was significantly lower in Storz Miller compared with Macintosh, Miller, and McGrath laryngoscopes (0.96 +/- 1.04, 1.67 +/- 1.15, 1.38 +/- 1.05, 1.42 +/- 1.27, respectively; P < 0.01). CONCLUSION: Storz Miller laryngoscope was found to have advantages over the other laryngoscopes in regard to glottic view, duration of successful intubation, number of attempts, dental trauma severity, need for additional maneuvers, and ease of use. PMID- 24215653 TI - Symptoms of posttraumatic stress, depression, and body image distress in female victims of physical and sexual assault: exploring integrated responses. AB - While body image concerns and interpersonal violence exposure are significant issues for women, their interrelationship has rarely been explored. We examined the associations between severity of acute injuries, symptoms of posttraumatic stress disorder (PTSD), depression, and body image distress within a sample of predominantly African American victims of interpersonal violence (N = 73). Severity of body image distress was significantly associated with each outcome. Moreover, body image distress was a significant, unique predictor of depression but not PTSD severity. We recommend continued exploration of body image concerns to further integrated research on violence against women. PMID- 24215654 TI - Analysis of catalase SNP rs1001179 in Saudi patients with primary open angle glaucoma. AB - PURPOSE: To investigate whether the g.4760C > T mutation in the catalase gene (CAT) is a risk factor for primary open angle glaucoma (POAG) in the Saudi population. METHODS: A cohort of 225 unrelated POAG patients and 403 unrelated control subjects from Saudi Arabia were genotyped for a single nucleotide polymorphism (SNP; rs1001179; g.4760C > T) in the CAT gene utilizing Taq-Man(r) assay. The association between mutant genotypes and various clinical indices important for POAG was also investigated. RESULTS: The distribution of different genotypes was comparable between both study groups. The genotype "C/C" was predominant among cases; 169 (75.1%) as well as among the controls; 289 (71.7%). As for the heterozygous mutated genotype "C/T", it was present in 52 (23.1%) of cases and 103 (25.6%) of controls, where the homozygous fully mutated genotype was present in only 4 (1.8%) of cases and 11 (2.7%) of the controls. The distribution of mutant allele was similar in both study groups (p = 0.218). Interestingly, there was a trend of association between the type of the mutation (homozygous versus heterozygous) and three clinical parameters important for predicting the severity of the disease. These parameters include mean age of onset, mean level of intraocular pressure (IOP) and mean months of duration of encountering glaucoma. CONCLUSIONS: There were no statistically significant differences between cases and controls in terms of the different genotype distribution. This mutation is possibly associated with various clinical indices important for POAG and thus may be used as a parameter for assessing POAG severity, at least in this population. PMID- 24215655 TI - A feasibility study of expert patient and community mental health team led bipolar psychoeducation groups: implementing an evidence based practice. AB - BACKGROUND: Group psychoeducation is a cost effective intervention which reduces relapse and improves functioning in bipolar disorder but is rarely implemented. The aim of this study was to identify the acceptability and feasibility of a group psychoeducation programme delivered by community mental health teams (CMHTs) and peer specialist (PS) facilitators. Organisational learning was used to identify and address systematically barriers and enablers, at organisational, health professional and patient levels, to its implementation into a routine service. METHODS: A systematic examination of barriers and enablers to a three day training process informed the delivery of a first treatment group and a similar process informed the delivery of the second treatment group. Triangulation of research methods improved its internal validity: direct observation of training, self-rated surveys of participant experiences, group discussion, and thematically analysed individual participant and facilitator interviews were employed. RESULTS: Barriers and enablers were identified at organisational, educational, treatment content, facilitator and patient levels. All barriers under the control of the research team were addressed with subsequent improvements in patient knowledge about the condition and about local service. In addition, self-management, agency and altruism were enhanced. Barriers that could not be addressed required senior clinical and education leadership outside the research team's control. PS and professional facilitators were successfully trained and worked together to deliver groups which were generally reported as being beneficial. CONCLUSION: Psychoeducation groups involving CMHT and PS facilitators is acceptable and feasible but their sustainment requires senior leadership within and outside the organisation that control finance and education services. PMID- 24215656 TI - Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice. AB - This study investigated the radioprotective effects of a naturally occurring dipeptide, carnosine, on testicular damage. Carnosine was administered (10, 50 and 100 mg kg(-1) body weight) to male mice via intraperitoneal injection for 4 days prior to gamma irradiation (2 Gy). Apoptosis with the TUNEL assay and histopathological parameters were evaluated 12-h and 14-day post-irradiation. Pre treatment with carnosine before irradiation significantly reduced the frequency of TUNEL-positive cells induced by radiation treatment at all doses by reduction factors of 1.8, 2.47 and 2.23 for carnosine at 10, 50 and 100 mg kg(-1) bw, respectively, unlike that observed in the radiation alone group. Exposure to ionising radiation decreased sperm count and reduced the height and diameter of seminiferous epithelial tubules. Pre-treatment with all doses of carnosine significantly augmented seminiferous epithelial height and tubule diameter and also increased the number of germinal cells in comparison to the group treated with radiation only. These results indicate that carnosine prevents testicular dysfunction induced by gamma-irradiation via an anti-apoptotic effect; this restoration of proper testicular function ultimately leads to the recovery of spermatogenesis. PMID- 24215657 TI - OCT1 genetic variants are associated with long term outcomes in imatinib treated chronic myeloid leukemia patients. AB - OBJECTIVES: One third of CML patients treated with first line imatinib have suboptimal responses or treatment failures with increased risk for disease progression. Imatinib is actively transported into cells by the SLC22A1 transporter (hOCT1) and its genetic variants may affect intracellular drug import. We studied the effect of SLC22A1 genetic variants on long-term outcomes of imatinib treated patients. METHODS: A total of 167 patients, 94% in chronic phase, were analyzed for rs41267797, rs683369, rs12208357, and rs628031 variants using the Sequenom MassARRAY platform. RESULTS: Rates of CHR, MCyR, CCyR, and MMolR were not significantly different according to allelic variants. However, patients with AA or GA rs628031 genotypes had a higher incidence of poor response to imatinib compared to the GG genotype (47% compared to 29%, P = 0.06), and a higher rate of KD mutation discovery (8/16 vs. 5/27, P = 0.04), suggesting that secondary resistance was more common in these genotypes. Median EFS was shorter for rs628031 genotype AA/AG compared with the GG genotype (61 months and not reached, respectively, P = 0.05), and 5 yr OS rates were lower for patients with the rs628031 genotypes AA/AG compared with the GG genotype (88% and 97%, respectively, P = 0.03). Patients with AA/GA rs628031 and additional rare genotypes had worse EFS and OS compared to patients with only AA/GA rs628031 (P = 0.02 for EFS and 0.01 for OS). There was no difference in pretreatment SLC22A1 mRNA expression levels in patients with rs628031 genotypes GG/AA or GA. CONCLUSIONS: Studying SLC22A1 genetic variants prior to TKI initiation could influence treatment decisions. PMID- 24215658 TI - The rice RING E3 ligase, OsCTR1, inhibits trafficking to the chloroplasts of OsCP12 and OsRP1, and its overexpression confers drought tolerance in Arabidopsis. AB - Plant growth under low water availability adversely affects many key processes with morphological, physiological, biochemical and molecular consequences. Here, we found that a rice gene, OsCTR1, encoding the RING Ub E3 ligase plays an important role in drought tolerance. OsCTR1 was highly expressed in response to dehydration treatment and defense-related phytohormones, and its encoded protein was localized in both the chloroplasts and the cytosol. Intriguingly, the OsCTR1 protein was found predominantly targeted to the cytosol when rice protoplasts transfected with OsCTR1 were treated with abscisic acid (ABA). Several interacting partners were identified, which were mainly targeted to the chloroplasts, and interactions with OsCTR1 were confirmed by using biomolecular fluorescence complementation (BiFC). Interestingly, two chloroplast-localized proteins (OsCP12 and OsRP1) interacted with OsCTR1 in the cytosol, and ubiquitination by OsCTR1 led to protein degradation via the Ub 26S proteasome. Heterogeneous overexpression of OsCTR1 in Arabidopsis exhibited hypersensitive phenotypes with respect to ABA-responsive seed germination, seedling growth and stomatal closure. The ABA-sensitive transgenic plants also showed improvement in their tolerance against severe water deficits. Taken together, our findings lend support to the hypothesis that the molecular functions of OsCTR1 are related to tolerance to water-deficit stress via ABA-dependent regulation and related systems. PMID- 24215659 TI - Evaluation of the clinical photographs in the Journal of Oral and Maxillofacial Surgery: from readers' perspectives. AB - PURPOSE: This study was designed to evaluate clinical photographs published in the Journal of Oral and Maxillofacial Surgery (JOMS) and understand the current status of oral and maxillofacial surgery. MATERIALS AND METHODS: A total of 1,317 photographs from the JOMS Volume 69 were assessed. These photographs were scored from 1 to 10 for the following parameters: sharpness; depth of field; exposure; composition; color or grayscale; background; position; distortion; label consistency; and white balance. Then, the distributions of scores were analyzed. Each score was compared with the average score. The effects of different subjects; emergency or nonemergency situations; and intraoperative, preoperative, or postoperative conditions on the quality of photographs were analyzed by conducting a nonparametric Kruskal-Wallis test. RESULTS: The total score of each photograph showed a left-skewed distribution, varying from 3 to 10, with an average score of 6.82. Four parameters, including sharpness, depth of field, exposure, and white balance, scored less than the average score. Photographs with an intraoral subject yielded the lowest score, with a significant difference (P < .05). The score of photographs taken during a nonemergency situation was significantly higher than that during an emergency situation (6.84 vs 6.03; P < .001). Photographs of an intraoperative condition yielded a score significantly lower than those of pre- and postoperative conditions (6.53 vs 7.11 and 6.75, respectively; P < .001). Approximately 45.5% of photographs (148 of 325) displayed uncovered eyes and 57.1% of specimens (40 of 70) did not appear with a plotting scale. CONCLUSIONS: Sharpness, depth of field, exposure, and white balance should be considered to a greater extent than the other parameters when oral and maxillofacial photographs are taken, particularly for intraoral conditions, emergency situations, and intraoperative conditions. Enhanced parameters and protection of a patient's identity may significantly improve the average level of photographic quality. PMID- 24215660 TI - A rare case of intraoral nodular fasciitis: diagnosis and immunohistochemical profile. AB - Nodular fasciitis is a benign, idiopathic, reactive proliferation of myofibroblasts found in the subcutaneous fascia; intraoral occurrence is very rare. An 18-year-old woman was referred to the oral diagnosis service with a 1 month history of a nodular mass in the gingiva. Clinical examination disclosed a well-circumscribed, mobile, pedunculated mass in the left mandibular gingiva. The clinical diagnoses included pyogenic granuloma. She underwent an excisional biopsy under local anesthesia through an intraoral approach. Microscopic examination showed a proliferation of spindle cells arranged in intersecting fascicles. The spindle cells exhibited plump, vesicular nuclei without significant pleomorphism. Scattered multinucleated giant cells also were present. Immunohistochemical stains showed that the lesional cells were positive for smooth muscle actin and vimentin and negative for S-100 protein. The features were those of an inflammatory, benign myofibroblastic lesion, consistent with intraoral nodular fasciitis. PMID- 24215661 TI - Primary neuroendocrine carcinoma in oral cavity: two case reports and review of the literature. AB - Neuroendocrine carcinoma (NEC) is a tumor that occurs in different locations, particularly the lungs and larynx. The oral cavity is a rare site for a primary NEC. This report describes 2 cases of primary NEC in the oral cavity. Case 1 occurred in the anterior mandibular gingiva in a 25-year-old woman and presented with a special histologic appearance. This patient showed no evidence of recurrence 13 months after marginal resection of the anterior mandible. Case 2 was a primary NEC with some foci of squamous cell differentiation arising in the right buccal region in a 38-year-old woman. This patient showed no evidence of disease 8 months after tumor resection and postoperative iodine-125 brachytherapy. To the best of the authors' knowledge, case 1 is the youngest patient with NEC reported in the oral cavity to date in the English-language literature, and case 2 is the first report of a primary NEC in the buccal region. PMID- 24215662 TI - A novel model mouth system for evaluation of In Vitro release of nicotine from moist snuff. AB - BACKGROUND: Pouch moist snuff, as a form of oral smokeless tobacco products, is becoming increasingly popular in North America, Scandinavia (where it is known as Snus), South Asia and parts of Africa. User usually places a pouch between the upper jaw and cheek to obtain euphoria from tobacco, leading to partial intake of tobacco constituents. To evaluate user exposure to tobacco, an approach with a novel model mouth system was developed and applied to evaluate release of nicotine from the pouch. RESULTS: A novel model mouth system has been developed to evaluate release behavior of tobacco constituents in pouch moist snuff. The system consists of the release medium reservoir module, the flow speed control module, the temperature control module, nicotine release module, and release solution collection module, and simulates buccal condition in terms of temperature, saliva compositions, and the rate of saliva production, etc. Artificial saliva was used as the release medium to evaluate release of nicotine in pouch moist snuff. The optimized test condition was that the release temperature of 37 degrees C and the flow rate performed at 0.2 mL min-1 in the first 5 min and 0.1 mL min-1 in the next 55 min. The performance of the model mouth system was compared with in vivo data of nicotine release in human volunteers. Data from 23 brands of moist snuff indicated that nicotine release rates increased with extraction time and approximately 60-90% of nicotine was released after 30 min of extraction in most of the samples, and the release behavior of nicotine was affected by product weights, nicotine concentration, and product pH, etc. CONCLUSION: The model mouth system can be used to evaluate the release behavior of constituents in pouch moist snuff, especially those directly related to human health such as nicotine and tobacco specific nitrosamine (TSNA), etc. This indicated that the system is an alternative tool to evaluate user exposure to tobacco. With further testing and validation, the model mouth system can be applied in risk evaluation of smokeless tobacco products. PMID- 24215664 TI - The patient experience with fatigue and content validity of a measure to assess fatigue severity: qualitative research in patients with ankylosing spondylitis (AS). AB - BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disorder characterized by inflammation of the spine and large joints. Fatigue is a common symptom that many AS patients find significantly impacts their health-related quality of life. The Worst Fatigue - Numeric Rating Scale (WF-NRS) assesses the severity of this symptom during the previous 24-hour period. The objective of this study was to perform qualitative research to support the development and content validity of the WF-NRS. METHODS: Patients with AS were recruited from clinical sites in the U.S. for a qualitative study which first entailed concept elicitation interviews to gain understanding of the patients' experience with AS and fatigue. Subsequently, cognitive debriefing interviews were undertaken to assess the understandability, clarity, and appropriateness from the patient's perspective, of the content of a measure of fatigue severity. RESULTS: Thirteen patients with AS participated in concept elicitation interviews and cognitive debriefing of the Brief Fatigue Inventory (BFI) fatigue severity subscale. The WF-NRS was developed from the worst fatigue item of the BFI as patients generally reported it to be understandable and covered an important concept, the completion instructions were modified, but the response scale remained as it was familiar and readily completed, and the recall period was appropriate. CONCLUSIONS: Patient responses resulted in the development of and supported the content validity of the WF-NRS. Further quantitative evaluation of the WF-NRS is warranted in order to assess its psychometric properties and confirm its usefulness as a clinical trial tool. PMID- 24215665 TI - Supplemental care from a bioethical perspective. AB - OBJECTIVE: To describe and analyze, from the perspective of Intervention Bioethics, the legal, institutional and ethical contexts, the conflicts and regulations of supplemental health care in Brazil, since the approval of the regulatory law in 1998 until 2010. METHODS: Qualitative research, using Intervention Bioethics as the theoretical reference. Bibliographical and documental study of the legislation, regulations and assistential framework, as well as interviews with members of the Supplemental Health Board. RESULTS: There was improvement in the records and rules of action in private health companies, as well as flow of information, contractual and financial guarantees provided to consumers. Conflicts persist regarding access to services and procedures, price increases, policies on autonomy and medical fees. There is a dispute with the public sector regarding the network of health services, with rising costs and no improvement in quality of care. DISCUSSION: Private participation in health demands comparative assessments and improvement of public-private care regulation, as well as promoting greater balance in the funding and reevaluation of the health care model. CONCLUSION: It is necessary to review the regulatory framework considering the supplementary, complementary or duplicate characteristic of assistance, the social actors involved, bioethical and political issues regarding associations between Supplemental Health Care and the National Health System (SUS). PMID- 24215663 TI - Plasma neutrophil gelatinase-associated lipocalin in acute kidney injury superimposed on chronic kidney disease after cardiac surgery: a multicenter prospective study. AB - INTRODUCTION: Plasma neutrophil gelatinase-associated lipocalin (NGAL) is reportedly useful for post-cardiac surgery acute kidney injury (AKI). Although chronic kidney disease (CKD) is a strong risk factor for AKI development, no clinical evaluation of plasma NGAL has specifically examined AKI occurring in patients with CKD. This study evaluated plasma NGAL in AKI superimposed on CKD after cardiac surgery. METHODS: This study prospectively evaluated 146 adult patients with scheduled cardiac surgery at 2 general hospitals. Plasma NGAL was measured before surgery, at ICU arrival after surgery (0 hours), and 2, 4, 12, 24, 36, and 60 hours after ICU arrival. RESULTS: Based on the Kidney Disease Improving Global Outcomes (KDIGO) CKD guideline, 72 (49.3%) were diagnosed as having CKD. Of 146 patients, 53 (36.3%) developed AKI after surgery. Multiple logistic regression analysis revealed that preoperative plasma NGAL, estimated glomerular filtration rate (eGFR), and operation time are significantly associated with AKI occurrence after surgery. Plasma NGAL in AKI measured after surgery was significantly higher than in non-AKI irrespective of CKD complication. However, transient decrease of plasma NGAL at 0 to 4 hours was observed especially in AKI superimposed on CKD. Plasma NGAL peaked earlier than serum creatinine and at the same time in mild AKI and AKI superimposed on CKD with increased preoperative plasma NGAL (>300 ng/ml). Although AKI superimposed on CKD showed the highest plasma NGAL levels after surgery, plasma NGAL alone was insufficient to discriminate de novo AKI from CKD without AKI after surgery. Receiver operating characteristics analysis revealed different cutoff values of AKI for CKD and non-CKD patients. CONCLUSIONS: Results show the distinct features of plasma NGAL in AKI superimposed on CKD after cardiac surgery: 1) increased preoperative plasma NGAL is an independent risk factor for post-cardiac surgery AKI; 2) plasma NGAL showed an earlier peak than serum creatinine did, indicating that plasma NGAL can predict the recovery of AKI earlier; 3) different cutoff values of post-operative plasma NGAL are necessary to detect AKI superimposed on CKD distinctly from de novo AKI. Further investigation is necessary to confirm these findings because this study examined a small number of patients. PMID- 24215666 TI - Content validation of the 'Mosaic of Opinions About Abortion' (Mosai). AB - OBJECTIVE: This study aimed to develop and validate the contents of the Mosaico de Opinioes Sobre o Aborto Induzido (Mosai), a structured questionnaire intended to be used as a tool to collect information about the views of health professionals about the morality of abortion. METHODS: The contents of the first version of the questionnaire was developed based on the technique of thematic content analysis of books, articles, films, websites and newspapers reporting cases of abortion and arguing about their practice. The Mosai was composed of 6 moral dilemmas (vignettes) related to induced abortion, whose outcomes should be chosen by the respondents and could be justified by the classification of 15 patterns of arguments about the morality of abortion. In order to validate its contents, the questionnaire was submitted to the scrutiny of a panel of 12 experts, an intentional sample consisted of doctors, lawyers, ethicists, sociologists, nurses and statisticians, who evaluated the criteria of clarity of writing, relevance, appropriateness to sample and suitability to the fields. These scores were analyzed by the method of concordance rate, while the free comments were analyzed using the analysis technique content. RESULTS: All the moral dilemmas and arguments were considered valid according to the rate of agreement, however, some comments led to the exclusion of a dilemma about emergency contraception, among other changes. CONCLUSION: The content of Mosai was considered valid to serve as a tool to collect the opinions of healthcare professionals regarding the morality of abortion. PMID- 24215667 TI - Proposal for a unified selection to medical residency programs. AB - OBJECTIVE: This paper proposes the unification of entrance exams to medical residency programs (MRP) in Brazil. Problems related to MRP and its interface with public health problems in Brazil are highlighted and how this proposal are able to help solving these problems. METHODS: The proposal is to create a database to be applied in MRP unified exams. Some advantages of using the Item Response Theory (IRT) in this database are highlighted. RESULTS: The MRP entrance exams are developed and applied decentralized where each school is responsible for its examination. These exams quality are questionable. Reviews about items quality, validity and reliability of appliances are not common disclosed. CONCLUSION: Evaluation is important in every education system bringing on required changes and control of teaching and learning. The proposal of MRP entrance exams unification, besides offering high quality exams to institutions participants, could be as an extra source to rate medical school and cause improvements, provide studies with a database and allow a regional mobility. PMID- 24215668 TI - Temperature Changes in Cortical Bone after Implant Site Preparation Using a Single Bur versus Multiple Drilling Steps: An In Vitro Investigation. AB - OBJECTIVES: The study aims to test the hypothesis of no differences in temperature variation by using a single bur for implant site preparation as compared with conventional drilling sequence using multiple burs with incremental diameter. MATERIALS AND METHODS: Synthetic blocks of bone (type I density) were used for drilling procedures. THREE GROUPS WERE EVALUATED: Group 1 and Group 2 - drilling with three consecutive burs for a 4.1 mm cylindrical implant and for a 4.3 mm conical implant, respectively; Group 3 - drilling with a single bur for a 4.2 mm conical implant. For each group, 20 drilling procedures were performed without irrigation and 20 with external irrigation. The temperature in the cortical bone during osteotomy for implant site preparation was measured through a thermocouple. RESULTS: The mean temperatures and standard deviations for the drilling without irrigation were: 25.5 +/- 1.24 degrees C for Group 1; 28.1 +/- 1.76 degrees C for Group 2; 26.5 +/- 1.79 degrees C for Group 3. Considering the drilling with irrigation, the mean values and standard deviations were: 20.4 +/- 1.17 degrees C for Group 1; 22.2 +/- 1.38 degrees C for Group 2; 20.2 +/- 0.83 degrees C for Group 3. Groups 1 and 3 yielded similar results, while Group 2 displayed significantly higher temperature increase than the other two groups. CONCLUSIONS: The single bur drilling protocol did not produce greater bone heating than the conventional protocol and may be considered a safe procedure. PMID- 24215669 TI - 3D reconstruction techniques of human coronary bifurcations for shear stress computations. AB - BACKGROUND: Heterogeneity in plaque composition in human coronary artery bifurcations is associated with blood flow induced shear stress. Shear stress is generally determined by combing 3D lumen data and computational fluid dynamics (CFD). We investigated two new procedures to generate 3D lumen reconstructions of coronary artery bifurcations for shear stress computations. METHODS: We imaged 10 patients with multislice computer tomography (MSCT) and intravascular ultrasound (IVUS). The 3D reconstruction of the main branch was based on the fusion of MSCT and IVUS. The proximal part of side branch was reconstructed using IVUS data or MSCT data, resulting in two different reconstructions of the bifurcation region. The distal part of the side branch was based on MSCT data alone. The reconstructed lumen was combined with CFD to determine the shear stress. Low and high shear stress regions were defined and shear stress patterns in the bifurcation regions were investigated. RESULTS: The 3D coronary bifurcations were successfully generated with both reconstruction procedures. The geometrical features of the bifurcation region for the two reconstruction procedures did not reveal appreciable differences. The shear stress maps showed a qualitative agreement, and the low and high shear stress regions were similar in size and average shear stress values were identical. The low and high shear stress regions showed an overlap of approximately 75%. CONCLUSION: Reconstruction of the side branch with MSCT data alone is an adequate technique to study shear stress and wall thickness in the bifurcation region. The reconstruction procedure can be applied to further investigate the effect of shear stress on atherosclerosis in coronary bifurcations. PMID- 24215671 TI - [A new way to assess the risk during neurosurgical procedures]. PMID- 24215670 TI - The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel. AB - OBJECTIVE: To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. METHODS: Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors. Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of >=0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods. In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy? RESULTS: Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice. mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist. Structured and standardised reporting of prostate MRI is paramount. State of the art mpMRI is capable of localising small tumours for focal therapy. State of the art mpMRI is the technique of choice for follow up of focal ablation. CONCLUSIONS: The present evidence for MRI in focal therapy is limited. mpMRI is not accurate enough to consistently grade tumour aggressiveness. Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy. PMID- 24215672 TI - Involvement of the orphan nuclear receptor SF-1 in the effect of PCBs, DDT and DDE on the secretion of steroid hormones and oxytocin from bovine granulosa cells. AB - Polychlorinated biphenyls (PCBs), DDT and its metabolite (DDE) belong to estrogen like endocrine disruptors. However, though their activity is approximately 1000 fold lower than the activity of estradiol (E2), this steroid's high concentration in follicular fluid and incubation media does not inhibit the influence of these xenobiotics. It was hypothesized that these xenobiotics might affect Steroidogenic Factor-1 (SF-1) and impair ovary function. To test this hypothesis, granulosa cells were obtained from ovarian follicles >1 or <1cm in diameter, which were treated with PCB-77, PCB-153, DDT or DDE (each at 10ng/ml), alone or jointly with an SF-1 antagonist (F0160). Treatment with the SF-1 antagonist inhibited (P<0.05) the secretion of P4 from cells of both sizes of follicles, as induced (P<0.05) by an SF-1 activator (HxP), DDE or PCB-153. All xenobiotics and HxP stimulated (P<0.05) the synthesis and secretion of oxytocin (OT). However, the effect on mRNA expression for NP-I/OT, which is OT precursor, was inhibited (P<0.05) by F0160 in all cultures treated with PCB-77, except for granulosa cells derived from follicles <1cm. Moreover, F0160 inhibited the effect on OT secretion of HxP, as well as all xenobiotics except for PCB-77 and DDE, in granulosa cells derived from follicles <1cm. Xenobiotic treatment did not affect (P>0.05) the expression for SF-1 mRNA. It is suggested that the SF-1 receptor may be involved in the adverse effects of xenobiotics on P4 secretion as well as the synthesis and secretion of OT. PMID- 24215673 TI - Rohitukine, a chromone alkaloid and a precursor of flavopiridol, is produced by endophytic fungi isolated from Dysoxylum binectariferum Hook.f and Amoora rohituka (Roxb).Wight & Arn. AB - Rohitukine, a chromone alkaloid, has gained considerable international attention in recent years because of its novel semi-synthetic derivative, flavopiridol and P-276-00. Both these molecules are in advanced stages of clinical development and trial for cancer treatment. Recently, flavopiridol was approved as an orphan drug for treatment of chronic lymphocytic leukemia cancer. The natural occurrence of rohitukine is restricted to only four plant species, Amoora rohituka and Dysoxylum binectariferum (both from the Meliaceae family) and from Schumanniophyton magnificum and Schumanniophyton problematicum (both from the Rubiaceae family). Recently, an endophytic fungi isolated from D. binectariferum was reported to produce rohitukine in culture. In this study, we report the production of rohitukine and its subsequent attenuation by endophytic fungi, Fusarium oxysporum (MTCC-11383), Fusarium oxysporum (MTCC-11384) and Fusarium solani (MTCC-11385), all isolated from D. binectariferum and Gibberella fujikuroi (MTCC-11382) isolated from Amoora rohituka. The fungal rohitukine which was analyzed by HPLC, LC-MS and LC-MS/MS was identical to reference rohitukine and that produced by the plant. The rohitukine content in the mycelial samples ranged from 192.78MUg to 359.55MUg100g(-1) of dry weight of and in broth it ranged from 14.10 to 71.90MUg100ml(-1). In all the fungal cultures, the production declined from first to fourth sub-culture. Studies are underway to unravel the mechanism by which the fungi produce the host metabolite in culture. PMID- 24215674 TI - Novel synthetic oleanane triterpenoid AMR-MeOAc inhibits K-Ras through ERK, Akt and survivin in pancreatic cancer cells. AB - K-Ras activating mutations are a major problem that drives aggressive tumor growth and metastasis in pancreatic cancer. Currently, there are no effective targeted therapies for this genetically defined subset of cancers harboring oncogenic K-Ras mutations that confer drug resistance, aggressive tumor growth, metastasis and poor clinical outcome. We identified a novel synthetic oleanane triterpenoid compound designated AMR-MeOAc that effectively kills K-Ras mutant pancreatic cancer HPAF-II cells. The cytotoxic effects correlated with apoptosis induction, as was evidenced by increase of apoptosis cells upon the treatment of AMR-MeOAc in HPAF-II cells. Our studies revealed that AMR-MeOAc treatment inhibits cancer associated survival gene survivin. Moreover, AMR-MeOAc also led to down regulation of Akt, ERK1/2 and survivin protein levels. Our results indicate that AMR-MeOAc or its active analogs could be a novel class of anticancer agents against K-Ras driven human pancreatic cancer. PMID- 24215675 TI - Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids. AB - Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73+/-0.04 and 3.15+/-0.16MUM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds. PMID- 24215676 TI - A new HLA-A*03 null allele - A*03:162N caused by an exon 4 insertion and discovered during an external quality assessment exercise. AB - HLA-A*03:162N differs from A*03:01:01:01 by an exon 4, 664-665insCATG causing E198A and A199X. PMID- 24215677 TI - A comprehensive meta QTL analysis for fiber quality, yield, yield related and morphological traits, drought tolerance, and disease resistance in tetraploid cotton. AB - BACKGROUND: The study of quantitative trait loci (QTL) in cotton (Gossypium spp.) is focused on traits of agricultural significance. Previous studies have identified a plethora of QTL attributed to fiber quality, disease and pest resistance, branch number, seed quality and yield and yield related traits, drought tolerance, and morphological traits. However, results among these studies differed due to the use of different genetic populations, markers and marker densities, and testing environments. Since two previous meta-QTL analyses were performed on fiber traits, a number of papers on QTL mapping of fiber quality, yield traits, morphological traits, and disease resistance have been published. To obtain a better insight into the genome-wide distribution of QTL and to identify consistent QTL for marker assisted breeding in cotton, an updated comparative QTL analysis is needed. RESULTS: In this study, a total of 1,223 QTL from 42 different QTL studies in Gossypium were surveyed and mapped using Biomercator V3 based on the Gossypium consensus map from the Cotton Marker Database. A meta-analysis was first performed using manual inference and confirmed by Biomercator V3 to identify possible QTL clusters and hotspots. QTL clusters are composed of QTL of various traits which are concentrated in a specific region on a chromosome, whereas hotspots are composed of only one trait type. QTL were not evenly distributed along the cotton genome and were concentrated in specific regions on each chromosome. QTL hotspots for fiber quality traits were found in the same regions as the clusters, indicating that clusters may also form hotspots. CONCLUSIONS: Putative QTL clusters were identified via meta-analysis and will be useful for breeding programs and future studies involving Gossypium QTL. The presence of QTL clusters and hotspots indicates consensus regions across cultivated tetraploid Gossypium species, environments, and populations which contain large numbers of QTL, and in some cases multiple QTL associated with the same trait termed a hotspot. This study combines two previous meta-analysis studies and adds all other currently available QTL studies, making it the most comprehensive meta-analysis study in cotton to date. PMID- 24215678 TI - Functional outcomes in patients with Borrelia burgdorferi reinfection. AB - When Lyme disease is treated with appropriate antibiotic therapy in the early stages, long-term outcomes are good. However, a few patients have persistent symptoms despite appropriate therapy. Whether these patients' symptoms are any different from those of patients with reinfection is unclear. Our objective was to compare long-term symptoms and functional outcomes of patients with Borrelia burgdorferi reinfection with those of patients with only 1 episode of infection and with no history of infection. We compared outcomes of Lyme reinfection patients, characterized by recurrent erythema migrans (EM) lesions, with those of patients with 1 episode of Lyme disease (Lyme control) and with no history of Lyme disease (non-Lyme control) by retrospective medical record review and a survey consisting of a 36-item Short-Form Health Survey (SF-36) and a 10-item symptom questionnaire. Analysis of variance (ANOVA) for continuous variables and chi(2) analysis for categorical variables were used. In cases of low cell counts, Fisher's exact tests were used. Bonferroni correction was used for multiple comparisons when ANOVA was significant. Reinfection was identified in 23/673 (3.4%) patients who had a diagnosis of Lyme disease in our health system during 2000-2004. Of the 23, 15 had long-term follow-up data and were age- and sex matched to 45 Lyme control and 60 non-Lyme control group patients. Clinical characteristics were similar in the reinfection and Lyme control groups. SF-36 results were similar between groups for all domains except energy/vitality (VT). The SF-36 domain of VT was significantly different between groups: 63.0 vs. 54.5 vs. 64.5 in the reinfection, Lyme control, and non-Lyme control groups, respectively (p=0.047). Clinical features and long-term outcomes of patients with recurrent EM lesions were similar to those of the control groups and consistent with B. burgdorferi reinfection, not persistent infection. Patients with Lyme reinfection should be treated with antibiotic regimens similar to those used for patients with an initial episode of Lyme disease. PMID- 24215679 TI - Effect of sodium bicarbonate and beta-alanine supplementation on maximal sprint swimming. AB - BACKGROUND: This study examined the effect of simultaneous supplementation of extracellular buffer sodium bicarbonate (SB) and intracellular buffer beta alanine (BA) on maximal sprint swimming. METHODS: Thirteen competitive male swimmers completed 4 different treatments (placebo [PL], SB, BA + PL, and BA + SB) in a crossover procedure. PL or SB supplementation (0.3 g/kg body weight) was ingested 60 min before two maximal 100-m freestyle swims that were performed with a passive recovery of 12-min between each swim. Because of the known long washout period for carnosine, four weeks of BA supplementation (4.8 g per day) was started after the first week of PL or SB supplementation and performance testing. RESULTS: The first maximal swims were similar, but the increase in time of the second versus the first 100-m swimming time was 1.5 s more (p < 0.05) in PL than in SB. Blood pH values were significantly (p < 0.05) greater in the SB and in the BA + SB groups compared to the PL and BA + PL values. There were no differences in peak blood lactate between the treatments. CONCLUSION: Supplementing with SB prior to performing maximal sprint swimming with repetitions under 60 s improves performance. However, co-supplementation with SB and BA did not confer any added benefit on maximal swim performance. PMID- 24215680 TI - Adult recollections of childhood memories: What details can be recalled? AB - In a memory survey, adult respondents recalled, dated, and described two earliest positive and negative memories that they were highly confident were memories. They then answered a series of questions that focused on memory details such as clothing, duration, weather, and so on. Few differences were found between positive and negative memories, which on average had 4/5 details and dated to the age of 6/6.5 years. Memory for details about activity, location, and who was present was good; memory for all other details was poorer or at floor. Taken together, these findings indicate that (full) earliest memories may be considerably later than previously thought and that they rarely contain the sort of specific details targeted by professional investigators. The resulting normative profile of memory details reported here can be used to evaluate overly specific childhood autobiographical memories and to identify memory details with a low probability of recall. PMID- 24215681 TI - Cardiovascular risk factors in a Mexican middle-class urban population. The Lindavista Study. Baseline data. AB - INTRODUCTION AND OBJECTIVE: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. METHODS: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. RESULTS: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol >= 200 mg/dL; 62% showed HDL-c levels<40 mg/dL; 52% triglycerides>150 mg/dL, and 34% levels of LDL c >= 160 mg/dL. Half of the population studied had the metabolic syndrome. CONCLUSION: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors. PMID- 24215682 TI - [Cardiopulmonary complications in sickle cell anemia]. AB - Sickle cell anemia, considered the most prevalent genetic disease among African Americans, is a disease with autosomal recessive inheritance pattern, characterized by the production of hemoglobin S. This abnormal protein polymerizes and facilitates the formation of fibrillar aggregates that alters the erythrocyte morphology. The stiffness of the red blood cells hinders the adequate transit across microcirculation, leading to hemolysis and increased blood viscosity, which ease thrombogenesis and vascular occlusion, resulting in tissue ischemia and microinfarcts. This disease has a high rate of morbidity and mortality, especially in the first three years of life, when a rapid diagnosis and appropriate treatment are essential. Cardiovascular complications such as heart failure and pulmonary hypertension may develop independently, and each one contributes to increased mortality, being the combination of both risk factors, an important aggravating factor for prognosis and a determinant indicator of mortality. PMID- 24215684 TI - Effect of spinach cultivar and bacterial adherence factors on survival of Escherichia coli O157:H7 on spinach leaves. AB - Similar to phytopathogens, human bacterial pathogens have been shown to colonize the plant phylloplane. In addition to environmental factors, such as temperature, UV, relative humidity, etc., the plant cultivar and, specifically, the leaf blade morphological characteristics may affect the persistence of enteropathogens on leafy greens. This study was conducted to evaluate the effect of cultivar dependent leaf topography and the role of strain phenotypic characteristics on Escherichia coli O157:H7 persistence on organic spinach. Spinach cultivars Emilia, Lazio, Space, and Waitiki were experimentally inoculated with the foodborne E. coli O157:H7 isolate EDL933 and its isogenic mutants deficient in cellulose, curli, or both curli and cellulose production. Leaves of 6-week-old plants were inoculated with 6.5 log CFU per leaf in a biosafety level 2 growth chamber. At 0, 1, 7, and 14 days, E. coli O157:H7 populations were determined by plating on selective medium and verified by laser scanning confocal microscopy. Leaf morphology (blade roughness and stoma density) was evaluated by low temperature and variable-pressure scanning electron microscopy. E. coli O157:H7 persistence on spinach was significantly affected by cultivar and strain phenotypic characteristics, specifically, the expression of curli. Leaf blade roughness and stoma density influenced the persistence of E. coli O157:H7 on spinach. Cultivar Waitiki, which had the greatest leaf roughness, supported significantly higher E. coli O157:H7 populations than the other cultivars. These two morphological characteristics of spinach cultivars should be taken into consideration in developing intervention strategies to enhance the microbial safety of leafy greens. PMID- 24215683 TI - Contributing factors in restaurant-associated foodborne disease outbreaks, FoodNet sites, 2006 and 2007. AB - An estimated 48 million cases of foodborne illness occur each year in the United States, resulting in approximately 128,000 hospitalizations and 3,000 deaths. Over half of all foodborne disease outbreaks reported to the Centers for Disease Control and Prevention are associated with eating in restaurants or delicatessens. We reviewed data from restaurant-associated foodborne disease outbreaks to better understand the factors that contribute to these outbreaks. Data on restaurant-associated foodborne disease outbreaks reported by sites participating in the Foodborne Diseases Active Surveillance Network (FoodNet) were analyzed to characterize contributing factors reported in foodborne disease outbreaks and the levels of evidence used to identify these factors. Of 457 foodborne disease outbreaks reported in 2006 and 2007 by FoodNet sites, 300 (66%) were restaurant associated, and of these 295 (98%) had at least one reported contributing factor. One to nine (with a median of two) contributing factors were reported per outbreak. Of the 257 outbreaks with a single etiology reported, contributing factors associated with food worker health and hygiene were reported for 165 outbreaks (64%), factors associated with food preparation practices within the establishment were reported for 88 outbreaks (34%), and factors associated with contamination introduced before reaching the restaurant were reported for 56 outbreaks (22%). The pronounced role of food workers in propagating outbreaks makes it clear that more work is needed to address prevention at the local level. Food workers should be instructed not to prepare food while ill to prevent the risk of transmitting pathogens. PMID- 24215685 TI - Efficacy of commercial produce sanitizers against nontoxigenic Escherichia coli O157:H7 during processing of iceberg lettuce in a pilot-scale leafy green processing line. AB - Chemical sanitizers are routinely used during commercial flume washing of fresh cut leafy greens to minimize cross-contamination from the water. This study assessed the efficacy of five commercial sanitizer treatments against Escherichia coli O157:H7 on iceberg lettuce, in wash water, and on equipment during simulated commercial production in a pilot-scale processing line. Iceberg lettuce (5.4 kg) was inoculated to contain 10(6) CFU/g of a four-strain cocktail of nontoxigenic, green fluorescent protein-labeled, ampicillin-resistant E. coli O157:H7 and processed after 1 h of draining at ~22 degrees C. Lettuce was shredded using a commercial slicer, step-conveyed to a flume tank, washed for 90 s using six different treatments (water alone, 50 ppm of peroxyacetic acid, 50 ppm of mixed peracid, or 50 ppm of available chlorine either alone or acidified to pH 6.5 with citric acid [CA] or T-128), and then dried using a shaker table and centrifugal dryer. Various product (25-g) and water (50-ml) samples collected during processing along with equipment surface samples (100 cm(2)) from the flume tank, shaker table, and centrifugal dryer were homogenized in neutralizing buffer and plated on tryptic soy agar. During and after iceberg lettuce processing, none of the sanitizers were significantly more effective (P <= 0.05) than water alone at reducing E. coli O157:H7 populations on lettuce, with reductions ranging from 0.75 to 1.4 log CFU/g. Regardless of the sanitizer treatment used, the centrifugal dryer surfaces yielded E. coli O157:H7 populations of 3.49 to 4.98 log CFU/100 cm(2). Chlorine, chlorine plus CA, and chlorine plus T-128 were generally more effective (P <= 0.05) than the other treatments, with reductions of 3.79, 5.47, and 5.37 log CFU/ml after 90 s of processing, respectively. This indicates that chlorine-based sanitizers will likely prevent wash water containing low organic loads from becoming a vehicle for cross-contamination. PMID- 24215686 TI - Pickled egg production: inactivation rate of Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus during acidification step. AB - Based on current U.S. Food and Drug Administration acidified foods guidelines, regulatory approval of commercial pickled egg production without a final heat treatment requires challenge studies. We conducted challenge studies to verify common pickled egg processing parameters. Hard-boiled eggs were acidified in ambient temperature brine at a 60:40 egg/brine ratio. Four acidification treatments were studied in triplicate: 5% acetic acid (AA) or 2.5% AA brine with and without 0.05% sodium benzoate. These treatments resulted in 2% or 1% AA with or without 0.02% sodium benzoate, respectively, in the total system. Samples were stored at 7 degrees C until pH at the yolk center was <= 4.6; subsequently, samples were held at ambient temperature. Egg pH was measured at 24- to 48-h intervals until equilibrium pH was reached (4.0 and 4.4). Eggs and jar lids were challenged with separate pathogen cocktails (six strains and/or serovars) of Salmonella enterica, Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus. After 5 and 9 days, the pH fell below 4.6 in 2% AA and 1% AA eggs, respectively. Sodium benzoate did not affect acidification rate for these brine treatments (P >= 0.05), nor did sodium benzoate affect pathogen die off. E. coli O157:H7, Salmonella, and L. monocytogenes were undetectable (<1 CFU/g) in pickled eggs in 2% AA at 72 h; S. aureus was undetectable after 7 days. In 1% AA eggs, Salmonella was undetectable after 10 days. No pathogens were detectable after 14 days. No pathogens were detectable on lids within 72 h for the 2% AA treatment. Only S. aureus was detectable on lids after 72 h in the 1% AA treatment and died off rapidly at ambient temperature. Although pathogens began die-off under refrigeration, heat treatment (ambient temperature storage) was required to reach undetectable levels. Minimal inversion was adequate treatment for lids. Pickled eggs should be held under refrigeration for the length of time needed to acidify them to <= 4.6 and then held at ambient temperatures to ensure pathogen inactivation. PMID- 24215687 TI - Postenrichment population differentials using buffered Listeria enrichment broth: implications of the presence of Listeria innocua on Listeria monocytogenes in food test samples. AB - The recovery of low levels of Listeria monocytogenes from foods is complicated by the presence of competing microorganisms. Nonpathogenic species of Listeria pose a particular problem because variation in growth rate during the enrichment step can produce more colonies of these nontarget cells on selective and/or differential media, resulting in a preferential recovery of nonpathogens, especially Listeria innocua. To gauge the extent of this statistical barrier to pathogen recovery, 10 isolates each of L. monocytogenes and L. innocua were propagated together from approximately equal initial levels using the current U. S. Food and Drug Administration's enrichment procedure. In the 100 isolate pairs, an average 1.3-log decrease was found in the 48-h enrichment L. monocytogenes population when L. innocua was present. In 98 of the 100 isolate pairs, L. innocua reached higher levels at 48 h than did L. monocytogenes, with a difference of 0.2 to 2.4 log CFU/ml. The significance of these population differences was apparent by an increase in the difficulty of isolating L. monocytogenes by the streak plating method. L. monocytogenes went completely undetected in 18 of 30 enrichment cultures even after colony isolation was attempted on Oxoid chromogenic Listeria agar. This finding suggests that although both Listeria species were present on the plate, the population differential between them restricted L. monocytogenes to areas of the plate with confluent growth and that isolated individual colonies were only L. innocua. PMID- 24215688 TI - Listeria monocytogenes in five Sardinian swine slaughterhouses: prevalence, serotype, and genotype characterization. AB - In a 3-year study (2008 to 2011) to estimate the prevalence and the contamination sources of Listeria monocytogenes in pork meat in Sardinia, Italy, 211 samples were collected from five Sardinian swine slaughterhouses: 171 samples from slaughtered pigs and 40 from the slaughterhouse environment. Fifty L. monocytogenes isolates were characterized by PCR-based serotyping, presence of virulence-associated genes, and pulsed-field gel electrophoresis restriction analysis. The overall prevalence of L. monocytogenes was 33% in swine carcasses, 7% in cecal material, 23% on meat contact surfaces, and 25% on noncontact surfaces. Only two serotypes were detected: 1/2c (78%) and 1/2a (22%). In all, based on the presence of virulence-associated genes, eight pathogenic profiles were detected. Only 42% of all isolates carried the full complement of virulence associated genes and were allotted to profile 1. Six pulsed-field gel electrophoresis profiles persisted in the slaughterhouses; restriction profiles appeared to be specific to each plant. PMID- 24215689 TI - Mathematical models to predict kinetic behavior and growth probabilities of Listeria monocytogenes on pork skin at constant and dynamic temperatures. AB - In this study, mathematical models were developed to predict the growth probability and kinetic behavior of Listeria monocytogenes on fresh pork skin during storage at different temperatures. A 10-strain mixture of L. monocytogenes was inoculated on fresh pork skin (3 by 5 cm) at 4 log CFU/cm(2). The inoculated samples were stored aerobically at 4, 7, and 10 degrees C for 240 h, at 15 and 20 degrees C for 96 h, and at 25 and 30 degrees C for 12 h. The Baranyi model was fitted to L. monocytogenes growth data on PALCAM agar to calculate the maximum specific growth rate, lag-phase duration, the lower asymptote, and the upper asymptote. The kinetic parameters were then further analyzed as a function of storage temperature. The model simulated growth of L. monocytogenes under constant and changing temperatures, and the performances of the models were evaluated by the root mean square error and bias factor (Bf). Of the 49 combinations (temperature * sampling time), the combinations with significant growth (P < 0.05) of L. monocytogenes were assigned a value of 1, and the combinations with nonsignificant growth (P > 0.05) were given a value of 0. These data were analyzed by logistic regression to develop a model predicting the probabilities of L. monocytogenes growth. At 4 to 10 degrees C, obvious L. monocytogenes growth was observable after 24 h of storage; but, at other temperatures, the pathogen had obvious growth after 12 h of storage. Because the root mean square error value (0.184) and Bf (1.01) were close to 0 and 1, respectively, the performance of the developed model was acceptable, and the probabilistic model also showed good performance. These results indicate that the developed model should be useful in predicting kinetic behavior and calculating growth probabilities of L. monocytogenes as a function of temperature and time. PMID- 24215690 TI - Combined inhibitory effect against postharvest storage rots and their effects on postharvest quality parameters in cherry tomatoes by cassia oil and calcium chloride. AB - The inhibitory effect of cassia oil alone or in combination with calcium chloride (CaCl2) against Alternaria alternata in vitro and in vivo was assessed on cherry tomatoes. The results demonstrated that concentrations of CaCl2 ranging from 0.25 to 3% enhanced the inhibitory effects of 200 MUl of cassia oil per liter on the growth of A. alternata in vitro. The combination of 0.25% CaCl2 and 500 MUl of cassia oil per liter showed a significant inhibition effect on decay development in both wounded artificially infected and unwounded naturally infected fruit. Importantly, these treatments did not reduce the overall quality of tomatoes. Defense-related enzyme activities were also evaluated. The results indicated that cassia oil alone or in combination with CaCl2 significantly enhanced defense related enzyme activities, such as peroxidase and polyphenol oxidase. Together, these data suggest that the combination of cassia oil and CaCl2 may be an efficient method to limit cherry tomato decay caused by fungi. PMID- 24215691 TI - Control of postharvest fungal pathogens by antifungal compounds from Penicillium expansum. AB - The fungicidal effects of secondary metabolites produced by a strain of Penicillium expansum (R82) in culture filtrate and in a double petri dish assay were tested against one isolate each of Botrytis cinerea, Colletotrichum acutatum, and Monilinia laxa and six isolates of P. expansum, revealing inhibitory activity against every pathogen tested. The characterization of volatile organic compounds released by the R82 strain was performed by solid phase microextraction-gas chromatographic techniques, and several compounds were detected, one of them identified as phenethyl alcohol (PEA). Synthetic PEA, tested in vitro on fungal pathogens, showed strong inhibition at a concentration of 1,230 MUg/ml of airspace, and mycelium appeared more sensitive than conidia; nevertheless, at the concentration naturally emitted by the fungus (0.726 +/- 0.16 m g/ml), commercial PEA did not show any antifungal activity. Therefore, a combined effect between different volatile organic compounds produced collectively by R82 can be hypothesized. This aspect suggests further investigation into the possibility of exploiting R82 as a nonchemical alternative in the control of some plant pathogenic fungi. PMID- 24215692 TI - Food protective effects of the active constituent isolated from Ostericum praeteritum against the stored food mite, Tyrophagus putrescentiae. AB - The acaricidal effects of the active constituent isolated from Ostericum praeteritum oil and its derivatives were compared with that of benzyl benzoate using fumigant and contact toxicity bioassays against Tyrophagus putrescentiae mites. The active compound of O. praeteritum was isolated by various chromatographic techniques and was identified as 3-methylphenol (C7H8O). On the basis of 50 % lethal dose values, 3-methylphenol (1.42 MUg/cm(2)) was determined to be 9.18 times more effective than benzyl benzoate (13.04 MUg/cm(2)), followed by 6-fluoro-3-methylphenol (2.18 MUg/cm(2)), 4-isopropyl-3-methylphenol (2.53 MUg/ cm(2)), and 6-chloro-3-methylphenol (4.03 MUg/cm(2)), against Tyrophagus putrescentiae mites in the fumigant bioassay. In the contact toxicity bioassay, 3 methylphenol (1.03 MUg/cm(2)) was the most-toxic compound against T. putrescentiae mites, followed by 6-fluoro-3-methylphenol (2.09 MUg/cm(2)), 4 isopropyl-3-methylphenol (2.11 MUg/cm(2)), 6-chloro-3-methylphenol (3.78 MUg/cm(2)), and benzyl benzoate (10.33 MUg/cm(2)). These results indicate that the introduction of chloro, isopropyl, and fluoro functional groups to the 3 methylphenol skeleton increased the acaricidal activity. Therefore, 3 methylphenol and its derivatives could potentially be used as natural acaricides against T. purescentiae. PMID- 24215693 TI - Screening of extracts of leaves and stems of Psychotria spp. (Rubiaceae) against Sitophilus zeamais (Coleoptera: Curculionidae) and Spodoptera frugiperda (Lepidoptera: Noctuidae) for maize protection. AB - Sitophilus zeamais (Coleoptera: Curculionidae) and Spodoptera frugiperda (Lepidoptera: Noctuidae) are important economic pests of corn, Zea mays (Poaceae). Psychotria spp. (Rubiaceae) plants are rich in secondary metabolites that could be toxic against such pests. We have screened extracts from four species of Psychotria abundant in the Cerrado (Savannah-type) biome of Brazil for the toxicity to two insects. We found that extracts from leaves and stems had significant effects on the hatching rate, parameters of caterpillar body (weight and length and width of head capsule), repellency, and mortality of these two pests, although the effects varied according to the Psychotria species and plant source (stem or leaf). Extracts of the stems of Psychotria hoffmannseggiana and of Psychotria capitata were more toxic to S. zeamais and the stems of Psychotria goyazensis to S. frugiperda; therefore, such extracts could have the potential for use in integrated pest management schemes. PMID- 24215694 TI - Four-year monitoring of foodborne pathogens in raw milk sold by vending machines in Italy. AB - Prevalence data were collected from official microbiological records monitoring four selected foodborne pathogens (Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, and Campylobacter jejuni) in raw milk sold by self service vending machines in seven Italian regions (60,907 samples from 1,239 vending machines) from 2008 to 2011. Data from samples analyzed by both culture based and real-time PCR methods were collected in one region. One hundred raw milk consumers in four regions were interviewed while purchasing raw milk from vending machines. One hundred seventy-eight of 60,907 samples were positive for one of the four foodborne pathogens investigated: 18 samples were positive for Salmonella, 83 for L. monocytogenes, 24 for E. coli O157:H7, and 53 for C. jejuni in the seven regions investigated. No significant differences in prevalence were found among regions, but a significant increase in C. jejuni prevalence was observed over the years of the study. A comparison of the two analysis methods revealed that real-time PCR was 2.71 to 9.40 times more sensitive than the culture-based method. Data on consumer habits revealed that some behaviors may enhance the risk of infection linked to raw milk consumption: 37% of consumers did not boil milk before consumption, 93% never used an insulated bag to transport raw milk home, and raw milk was consumed by children younger than 5 years of age. These results emphasize that end-product controls alone are not sufficient to guarantee an adequate level of consumer protection. The beta distribution of positive samples in this study and the data on raw milk consumer habits will be useful for the development of a national quantitative risk assessment of Salmonella, L. monocytogenes, E. coli O157, and C. jejuni infection associated with raw milk consumption. PMID- 24215695 TI - Microbiological quality of milk in Tanzania: from Maasai stable to African consumer table. AB - In Tanzania, pastoralists such as the Maasai and small urban farmers are responsible for the country's milk production, and 95% of the national milk supply is sold without regulation. This study was conducted using hygiene checklists and milk sampling to investigate milk quality and safety at various steps throughout the milk production chain. In regions of Dar es Salaam and Lake Victoria, 196 milk samples were collected: 109 samples of raw milk, 41 samples of packed or open served heat-treated products, and 46 samples of fermented products. Samples were taken from (i) the production level (pastoralists and urban farmers), (ii) the collection level (middlemen and depots), (iii) processors (dairies), and (iv) retailers (kiosks). Samples were analyzed for hygiene criteria (total bacteria, total coliforms, Escherichia coli, and coagulase-positive staphylococci) and foodborne pathogens such as Salmonella, enterohemorrhagic E. coli O157:H7, and Listeria monocytogenes. Adequate heating of milk for drinking was determined via heat labile alkaline phosphatase and lactoperoxidase analysis. Total bacterial counts indicated that only 67% (73 of 109) of raw milk samples and 46% (19 of 41) of heat-treated samples met national Tanzanian standards. Bulk milk samples taken from the traditional milking vessels of Maasai pastoralists had the lowest total bacterial counts: >= 1 * 10(2) CFU/ml. Foodborne pathogens such as E. coli O157:H7 and Salmonella were isolated from 10.1% (11 of 109) of raw milk samples but were not detected in heat-treated or fermented products, and 83% of heat-treated milk samples were lactoperoxidase negative, indicating overpasteurization. Coliforms were detected in 41% (17 of 41) of processed milk samples, thus indicating a high rate of recontamination. A progressive decrease in microbial quality along the milk production chain was attributed to departures from traditional methods, inadequate milk containers, long transport distances, lack of cooling, and lack of a basic understanding of hygiene. PMID- 24215696 TI - Assessing the freshness of meat by using quantum-behaved particle swarm optimization and support vector machine. AB - To improve the performance of meat freshness identification systems, we present a new identification method based on quantum-behaved particle swarm optimization (QPSO) and the support vector machine (SVM). Fresh pork, beef, mutton, and shrimp samples were stored in a hypobaric chamber for several days, and the conventional indices of meat freshness, including total volatile basic nitrogen content, aerobic plate count, pH value, and sensory scores, were determined to achieve the identification of sample freshness. However, the experiments showed that it was difficult to obtain an ideal freshness assessment by any single physicochemical or sensory property. Therefore, SVM was introduced to use these data to build a freshness model. Furthermore, QPSO was proposed to seek the optimal parameter combination of SVM. The experimental results indicated that the hybrid SVM model with QPSO could be used to predict meat freshness with 100 % classification accuracy. PMID- 24215697 TI - Microbial stability and quality of seasoned cracked green Alorena table olives packed in diverse chloride salt mixtures. AB - This work was conducted to determine the effect of the partial replacement of NaCl by KCl and CaCl2 (expressed as percentages, wt/vol) on the microbial stability and physicochemical characteristics of seasoned cracked olives using a simplex centroid mixture design. Neither Enterobacteriaceae nor lactic acid bacteria were found during the 50 days that olive packages were monitored. Therefore, microbial instability was considered due to the growth of yeasts, which were the only detected microorganisms; Saccharomyces cerevisiae and Pichia membranifaciens were the most relevant species. Yeasts decreased during the first 21 to 30 days after packing, but their populations rose to 3.5 log CFU/ml by the end of the storage period, clearly causing product deterioration. The partial substitution of NaCl with the other chloride salts slightly altered the phase of microbial inhibition and regrowth. Most of the quality characteristics were not affected by the use of the alternative salt mixtures, but the pH values and Cl(-) concentrations in brine decreased as the CaCl2 concentration increased. Hence, seasoned cracked table olives can be produced using a lower proportion of NaCl without causing significant changes in the shelf life and product quality, although further detailed studies are necessary to guarantee the stability of products packed with specific salt mixtures. PMID- 24215698 TI - Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act. AB - To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures. PMID- 24215699 TI - Food safety practices among Norwegian consumers. AB - An informed consumer can compensate for several potential food safety violations or contaminations that may occur earlier in the food production chain. However, a consumer can also destroy the work of others in the chain by poor food handling practices, e.g., by storing chilled ready-to-eat foods at abusive temperatures. To target risk-reducing strategies, consumer groups with high-risk behavior should be identified. The aim of this study was to identify demographic characteristics associated with high-risk food handling practices among Norwegian consumers. More than 2,000 randomly selected Norwegian consumers were surveyed, and the results were analyzed with a risk-based grading system, awarding demerit points for self-reported food safety violations. The violations were categorized into groups, and an ordinary multiple linear regression analysis was run on the summarized demerit score for each group and for the entire survey group as a whole. Young and elderly men were identified as the least informed consumer groups with the most unsafe practices regarding food safety. Single persons reported poorer practices than those in a relationship. People with higher education reported poorer practices than those with lower or no education, and those living in the capital of Norway (Oslo) reported following more unsafe food practices than people living elsewhere in Norway. Men reported poorer food safety practices than women in all categories with two exceptions: parboiling raw vegetables before consumption and knowledge of refrigerator temperature. These findings suggest that risk-reducing measures should target men, and a strategy is needed to change their behavior and attitudes. PMID- 24215700 TI - Customizable PCR-microplate array for differential identification of multiple pathogens. AB - Customizable PCR-microplate arrays were developed for the rapid identification of Salmonella Typhimurium, Salmonella Saintpaul, Salmonella Typhi, Shigella dysenteriae, Escherichia coli O157:H7, Francisella tularensis subsp. tularensis, Francisella tularensis subsp. novicida, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia pestis, and Yersinia pseudotuberculosis. Previously, we identified highly specific primers targeting each of these pathogens. Here, we report the development of customizable PCR-microplate arrays for simultaneous identification of the pathogens using the primers identified. A mixed aliquot of genomic DNA from 38 strains was used to validate three PCR-microplate array formats. Identical PCR conditions were used to run all the samples on the three formats. Specific amplifications were obtained on all three custom plates. In preliminary tests performed to evaluate the sensitivity of these assays in samples inoculated in the laboratory with Salmonella Typhimurium, amplifications were obtained from 1 g of beef hot dog inoculated at as low as 9 CFU/ml or from milk inoculated at as low as 78 CFU/ml. Such microplate arrays could be valuable tools for initial identification or secondary confirmation of contamination by these pathogens. PMID- 24215701 TI - Prevalence and quantitative detection of Salmonella in retail raw chicken in Shaanxi, China. AB - Quantitative Salmonella concentrations and prevalence of Salmonella in raw chicken at the retail level in Shaanxi province, China, was determined in this study. Two hundred forty samples were collected in Yangling and the surrounding cities, in Shaanxi Province, China, for data collection over 12 successive months from April 2011 to March 2012. During the whole surveillance year, the overall Salmonella contamination rate of retail raw chicken was identified as 43.3%, the most-probable-number (MPN) values ranged from 0.0036 to 0.8596 MPN per g, and the average value was 0.1655 MPN per g, except in 11 of the samples, which had MPN values of more than 11 MPN per g. In April 2011, the highest prevalence rate, which was 80.0%, was observed, and the corresponding MPN value was 0.8596 MPN per g. Observed in November 2011, the lowest prevalence rate and the corresponding MPN value were 5.0% and 0.0036 MPN per g, respectively. Prevalence of Salmonella in chicken collected from the supermarket (49.2%) was higher but not significantly different from that in the wet markets (37.5%), although the MPN value of samples in the wet market (0.1912 MPN per g) was higher than that in the supermarket (0.1396 MPN per g). Prevalence of Salmonella was the highest in the frozen chicken (53.3%) compared with chilled chicken (45.0%) and freshly slaughtered chicken (37.5%); however, the MPN value of the freshly slaughtered chicken (0.1912 MPN per g) was higher than those of either frozen chicken (0.1804 MPN per g) or the chilled chicken (0.0988 MPN per g). PMID- 24215702 TI - Comparison of enrichment broths for the recovery of healthy and heat-injured Salmonella typhimurium on raw duck wings. AB - This study was performed to optimiz eSalmonella Typhimurium recovery from raw duck wings with five nonselective broths (buffered peptone water, tryptic soy broth, lactose broth, universal preenrichment broth, nutrient broth) and four selective broths (selenite broth, BAX System MP media [MP], Salmonella AD media [AD], ONE broth-Salmonella [OB]). Healthy or heat-injured (50 and 85% injury) cells were inoculated at a level of 10(2), 10(1), or 10(0) CFU/25 g on raw duck wings. Growth was modeled using DMfit with four growth parameters: lag-phase duration, maximum growth rate, doubling time, and maximum population density. Most enrichments were able to recover Salmonella Typhimurium to greater than 6 log CFU/ml. AD, MP, and OB had significantly (P < 0.05) higher maximum growth rate (0.9 to 1.0/h) and lower doubling time (0.7 to 0.8 h). Buffered peptone water, AD, MP, and OB recovered healthy and 50%-injured cells at low inoculum levels to more than 6.0 log CFU/ml; OB achieved the greatest recovery (7.6 and 7.9 log CFU/ml), following 24 h of incubation. The 85%-injured cells at 10(0) and 10(1) CFU/25 g, however, were only recovered in OB, reaching 7.3 and 7.5 log CFU/ml, respectively. These results suggest that OB may be an appropriate enrichment broth for the recovery of Salmonella Typhimurium from raw duck wings in standard diagnostic tests or other rapid detection methods, to avoid false negative results. PMID- 24215703 TI - Use of germicidal UV light to reduce low numbers of Listeria monocytogenes on raw chicken meat. AB - Listeria monocytogenes is a common constituent of the microbiological community in poultry processing plants and can be found in low numbers on raw poultry. Raw meat is the most important source of this pathogen in commercial cooking facilities. Germicidal UV light was tested as a means to kill L. monocytogenes inoculated onto broiler breast fillets. Treatments at 800 MUW/ cm(2) for 5 s to 5 min of exposure were tested against inocula of 35 to 60 cells per fillet. All fillets were sampled by rinsing in enrichment broth, and surviving pathogens were quantified using most-probable-number (MPN) analysis. Five replications each with 5 fillets per treatment were analyzed to achieve 25 sample fillets per treatment. All treatment times resulted in a significant decrease in L. monocytogenes numbers compared with paired untreated controls. Treated samples retained 0.2 to 1.5 MPN L. monocytogenes per fillet, and exposure time had no significant effect on the number of surviving cells. A 5-s treatment with germicidal UV light has potential as an intervention method to limit the transfer of L. monocytogenes on raw skinless breast fillets from a slaughter plant to a cooking plant. PMID- 24215704 TI - Inhibition of Clostridium perfringens growth by potassium lactate during an extended cooling of cooked uncured ground turkey breasts. AB - The U.S. Department of Agriculture's Food Safety and Inspection Service compliance guideline known as Appendix B specifies chilling time and temperature limits for cured and uncured meat products to inhibit growth of spore-forming bacteria, particularly Clostridium perfringens. Sodium lactate and potassium lactate inhibit toxigenic growth of Clostridium botulinum, and inhibition of C. perfringens has been reported. In this study, a cocktail of spores of three C. perfringens strains (ATCC 13124, ATCC 12915, and ATCC 12916) were inoculated into 100-g samples of ground skinless, boneless turkey breast formulated to represent deli-style turkey breast. Three treatment groups were supplemented with 0 (control), 1, or 2% potassium lactate (pure basis), cooked to 71 degrees C, and assayed for C. perfringens growth during 10 or 12 h of linear cooling to 4 degrees C. In control samples, populations of C. perfringens increased 3.8 to 4.7 log CFU/g during the two chilling protocols. The 1% potassium lactate treatment supported only a 2.5- to 2.7-log increase, and the 2% potassium lactate treatment limited growth to a 0.56- to 0.70-log increase. When compared with the control, 2% potassium lactate retarded growth by 2.65 and 4.21 log CFU/g for the 10- and 12-h cooling protocols, respectively. These results confirm that the addition of 2% potassium lactate inhibits growth of C. perfringens and that potassium lactate can be used as an alternative to sodium nitrite for safe extended cooling of uncured meats. PMID- 24215705 TI - Decontamination treatments for psychrotrophic microorganisms on chicken meat during storage at different temperatures. AB - The antimicrobial effectiveness of five chemical decontaminants (12 % trisodium phosphate [TSP], 1,200 ppm acidified sodium chlorite [ASC], 2 % citric acid [CA], 220 ppm of peroxyacids [PA], or 50 ppm of chlorine dioxide [CD]) against psychrotrophic populations on skinned chicken legs was assessed throughout 120 h of storage under various temperature abuse scenarios. Three different simulated cold chain disruptions were used: T1 (12 h at 1 +/- 1 degrees C, 6 h at 15 +/- 1 degrees C, and 102 h at 4 +/- 1 degrees C), T2 (18 h at 1 +/- 1 degrees C, 6 h at 15 +/- 1 degrees C, and 96 h at 10 +/- 1 degrees C), or T3 (18 h at 4 +/- 1 degrees C, 6 h at 20 +/- 1 degrees C, and 96 h at 7 +/- 1 degrees C). Microbiological analyses were carried out at 0, 24, 72, and 120 h of storage. Substantial microbial reductions, with respect to control (untreated) samples, were obtained in legs treated with TSP, ASC, and CA, with average values ranging from 1.54 +/- 1.52 to 2.02 +/- 2.19 log CFU/cm(2). TSP was the most effective compound under mild abuse temperature conditions (T1), with mean reductions of 2.01 +/- 1.67 log CFU/cm(2), whereas ASC, followed by CA, proved to be particularly useful under moderate abuse conditions (T3; average reductions of 2.99 +/- 2.27 and 1.98 +/- 1.65 log CFU/cm(2), respectively). Treatment with PA or CD resulted in minimal microbial reductions. PMID- 24215706 TI - Microbiological quality of Burrata cheese produced in Puglia region: southern Italy. AB - Burrata cheese is a popular typical Italian food product, produced in Puglia (an administrative region of southern Italy), and this study investigated the microbiological quality of 404 samples of this cheese. The samples were analyzed in order to quantify Escherichia coli and to detect the presence of Staphylococcus aureus, Salmonella spp., and Listeria monocytogenes. No sample exceeded the values of E. coli set by EC Regulation 1441/07 for some dairy products, while 15 (3.7%) samples tested coagulase-positive staphylococci positive, with values greater than 10(3) CFU/g. One strain of S. aureus was identified and characterized from each of these positive samples, and of these strains, 7 (46.6%) produced staphylococcal enterotoxin A, 5 (33.3%) produced staphylococcal enterotoxin C, 2 (13.3%) produced staphylococcal enterotoxin D, and 1 (6.6%) produced both staphylococcal enterotoxins A and D. All strains were mecA negative. The 15 S. aureus isolates were tested for their antimicrobial resistance patterns, and all analyzed strains showed antimicrobial resistance properties for at least one of the tested antibiotics. Testing for the other pathogens mentioned above gave negative results. The results of our study mean that the microbiological quality of Burrata cheese can be assumed to be good, although care must be taken with raw materials and good hygiene during processing in order to guarantee greater food safety. PMID- 24215707 TI - Di-(2-ethylhexyl) adipate in selected total diet food composite samples. AB - Polyvinyl chloride (PVC) food-wrapping films plasticized with di-(2-ethylhexyl) adipate (DEHA) are commonly used by grocery stores in Canada to rewrap meat, poultry, fish, cheese, and other foods. DEHA was assessed as part of the Government of Canada's Chemicals Management Plan. The main source of exposure for most age groups was expected to be food. Although the margin of exposure from food and beverages is considered to be adequately protective, the Government of Canada committed to performing targeted surveys of DEHA in foods and food packaging materials to better define Canadian exposure to DEHA through dietary intake. In order to determine whether more-comprehensive targeted surveys on DEHA in foods should be conducted, 26 food composite samples from the 2011 Canadian total diet study were selected and analyzed for DEHA using a method based on solvent and dispersive solid-phase extraction and gas chromatography-mass spectrometry. These 26 food composites include cheese, meat, poultry, fish, and fast foods, and PVC films were likely used in packaging the individual foods used to make the composites. DEHA was detected in most of the meat, poultry, and fish composite samples, with the highest concentration found in ground beef (11 MUg/g), followed by beef steak (9.9 MUg/g), freshwater fish (7.8 MUg/g), poultry liver pate (7.4 MUg/g), fresh pork (6.9 MUg/g), cold cuts and luncheon meats (2.8 MUg/g), veal cutlets (2.1 MUg/g), roast beef (1.3 MUg/g), lamb (1.2 MUg/g), and organ meats (0.20 MUg/g). Targeted surveys should be conducted to investigate the presence of DEHA in various foods packaged with PVC films in more detail and provide updated occurrence data for accurate human exposure assessment. PMID- 24215708 TI - Survey of food safety practices on small to medium-sized farms and in farmers markets. AB - As produce consumption has increased, so have foodborne disease outbreaks associated with fresh produce. Little research has addressed food safety practices used on small to medium-sized farms selling locally or in farmers markets. This study evaluated current food safety practices used by farmers on small to medium-sized farms and managers of farmers markets in Georgia, Virginia, and South Carolina based on responses to surveys. Surveys were developed, pretested, and revised before implementation with target audiences and were implemented via mail and the Web to maximize participation, with reminders sent to nonrespondents. Data were collected from 226 farmers and 45 market managers. Frequencies and percentages were calculated for all response variables. Responses from farmers indicated that more than 56% of them use manures. Of those who use manures, 34% use raw or mixtures of raw and composted manure, and over 26% wait fewer than 90 days between application of raw manure and harvest. Over 27% use water sources that have not been tested for safety for irrigation, and 16% use such water sources for washing produce. Over 43% do not sanitize surfaces that touch produce at the farm. Only 33% of farmers always clean transport containers between uses. Responses from market managers indicated that over 42% have no food safety standards in place for the market. Only 2 to 11% ask farmers specific questions about conditions on the farm that could affect product safety. Less than 25% of managers sanitize market surfaces. Only 11% always clean market containers between uses. Over 75% of markets offer no sanitation training to workers or vendors. While farmers and market managers are using many good practices, the results indicate that some practices being used may put consumers at risk of foodborne illness. Consequently, there is a need for training for both farmers and market managers. PMID- 24215709 TI - El Proceso Continuo de la caries: Oportunidades para Detectar, Tratar y Monitorear la Remineralizacion de las Lesiones de Caries en Estadio Temprano. PMID- 24215711 TI - Perforated duodenal ulcer presenting with a subphrenic abscess revealed by plain abdominal X-ray films and confirmed by multi-detector computed tomography: a case report. AB - INTRODUCTION: Peptic ulcer disease is still the major cause of gastrointestinal perforation despite major improvements in both diagnostic and therapeutic strategies. While the diagnosis of a perforated ulcer is straightforward in typical cases, its clinical onset may be subtle because of comorbidities and/or concurrent therapies. CASE PRESENTATION: We report the case of a 53-year-old Caucasian man with a history of chronic myeloid leukemia on maintenance therapy (100mg/day) with imatinib who was found to have a subphrenic abscess resulting from a perforated duodenal ulcer that had been clinically overlooked. Our patient was febrile (38.5 degrees C) with abdominal tenderness and hypoactive bowel sounds. On the abdominal plain X-ray films, a right subphrenic abscess could be seen. On contrast-enhanced multi-detector computed tomography, a huge air-fluid collection extending from the subphrenic to the subhepatic anterior space was observed. After oral administration of 500cm3 of 3 percent diluted diatrizoate meglumine, an extraluminal leakage of the water-soluble iodinated contrast media could then be appreciated as a result of a perforated duodenal ulcer. During surgery, the abscess was drained and extensive adhesiolysis had to be performed to expose the duodenal bulb where the ulcer was first identified by methylene blue administration and then sutured. CONCLUSIONS: While subphrenic abscesses are well known complications of perforated gastric or duodenal ulcers, they have nowadays become rare thanks to advances in both diagnostic and therapeutic strategies for peptic ulcer disease. However, when peptic ulcer disease is not clinically suspected, the contribution of imaging may be substantial. PMID- 24215710 TI - Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). AB - Ca(2+) flux through l-type CaV1.2 channels shapes the waveform of the ventricular action potential (AP) and is essential for excitation-contraction (EC) coupling. Timothy syndrome (TS) is a disease caused by a gain-of-function mutation in the CaV1.2 channel (CaV1.2-TS) that decreases inactivation of the channel, which increases Ca(2+) influx, prolongs APs, and causes lethal arrhythmias. Although many details of the CaV1.2-TS channels are known, the cellular mechanisms by which they induce arrhythmogenic changes in intracellular Ca(2+) remain unclear. We found that expression of CaV1.2-TS channels increased sarcolemmal Ca(2+) "leak" in resting TS ventricular myocytes. This resulted in higher diastolic [Ca(2+)]i in TS ventricular myocytes compared to WT. Accordingly, TS myocytes had higher sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+) spark activity, larger amplitude [Ca(2+)]i transients, and augmented frequency of Ca(2+) waves. The large SR Ca(2+) release in TS myocytes had a profound effect on the kinetics of CaV1.2 current in these cells, increasing the rate of inactivation to a high, persistent level. This limited the amount of influx during EC coupling in TS myocytes. The relationship between the level of expression of CaV1.2-TS channels and the probability of Ca(2+) wave occurrence was non-linear, suggesting that even low levels of these channels were sufficient to induce maximal changes in [Ca(2+)]i. Depolarization of WT cardiomyocytes with a TS AP waveform increased, but did not equalize [Ca(2+)]i, compared to depolarization of TS myocytes with the same waveform. We propose that CaV1.2-TS channels increase [Ca(2+)] in the cytosol and the SR, creating a Ca(2+)overloaded state that increases the probability of arrhythmogenic spontaneous SR Ca(2+) release. PMID- 24215712 TI - Wild type and mutant amyloid precursor proteins influence downstream effects of proteasome and autophagy inhibition. AB - Cells rely on complementary proteolytic pathways including the ubiquitin proteasome system and autophagy to maintain proper protein degradation. There is known to be considerable interplay between them, whereby the loss of one clearance system results in compensatory changes in other proteolytic pathways of the cell. Disturbances in proteolysis are known to occur in Alzheimer's disease, and potentially contribute to neurophysiological and neurodegenerative processes. Currently, few data are available on how the presence of wild type and mutant amyloid precursor protein (APPwt and APPmut) potentially alters the reciprocal interplay between the different intracellular proteolytic pathways. This study used human SH-SY5Y neuronal cell lines, and SH-SY5Y transfected with either APPwt or APPmut (valine-to-glycine substitution at position 717), in order to explore if the presence of APPwt or APPmut altered the downstream effects of pharmacological proteasome or autophagy inhibition. The occurrence of APPwt or APPmut was observed to disturb proteasome or autophagy activities upon treatment with proteasome inhibitors or authophagy inhibitors. Interestingly, APPwt and APPmut expression was observed to significantly and robustly enhance the induction in cathepsin B following the administration of an established proteasome inhibitor. The presence of APPwt and APPmut also significantly reduced the elevation in ubiquitinated proteins following proteasome inhibitor treatments. Our data strongly suggest that APP is able to affect the downstream effects of protease inhibition in neural cells including enhancement of cathepsin B activity, with these changes in cathepsin B significantly and inversely related to the levels of ubiquitinated protein. PMID- 24215714 TI - Chronic myeloid leukemia in lymphoid blast crisis. PMID- 24215713 TI - Classical NF-kappaB activation impairs skeletal muscle oxidative phenotype by reducing IKK-alpha expression. AB - BACKGROUND: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-kappaB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Interestingly, IkappaB kinase alpha (IKK-alpha: a key kinase in the alternative NF-kappaB pathway) was recently identified as a novel positive regulator of skeletal muscle OXPHEN. We hypothesised that inflammation-induced classical NF-kappaB activation contributes to loss of muscle OXPHEN in COPD by reducing IKK-alpha expression. METHODS: Classical NF-kappaB signalling was activated (molecularly or by tumour necrosis factor alpha: TNF alpha) in cultured myotubes and the impact on muscle OXPHEN and IKK-alpha levels was investigated. Moreover, the alternative NF-kappaB pathway was modulated to investigate the impact on muscle OXPHEN in absence or presence of an inflammatory stimulus. As a proof of concept, quadriceps muscle biopsies of COPD patients and healthy controls were analysed for expression levels of IKK-alpha, OXPHEN markers and TNF-alpha. RESULTS: IKK-alpha knock-down in cultured myotubes decreased expression of OXPHEN markers and key OXPHEN regulators. Moreover, classical NF kappaB activation (both by TNF-alpha and IKK-beta over-expression) reduced IKK alpha levels and IKK-alpha over-expression prevented TNF-alpha-induced impairments in muscle OXPHEN. Importantly, muscle IKK-alpha protein abundance and OXPHEN was reduced in COPD patients compared to controls, which was more pronounced in patients with increased muscle TNF-alpha mRNA levels. CONCLUSION: Classical NF-kappaB activation impairs skeletal muscle OXPHEN by reducing IKK alpha expression. TNF-alpha-induced reductions in muscle IKK-alpha may accelerate muscle OXPHEN deterioration in COPD. PMID- 24215715 TI - Immediate Loading of Two Dental Implants, in Edentulous Mandibles, with Locator(r) Attachments or Dolder(r) Bars: First Results from a Prospective Randomized Clinical Study. AB - OBJECTIVE: The study aims to evaluate survival and the incidence of complications for pairs of implants placed in the frontal area of edentulous mandibles and immediately loaded with either bar or Locator(r) (Zest Anchors LLC, Escondido, CA, USA) attachments. MATERIAL AND METHODS: Forty-six patients (mean age 69.4 years; 73.9% male) with edentulous mandibles each received two immediately loaded implants in the interforaminal area of the symphysis. Immediately after implant placement, Dolder(r) bar (Sub-Tec Wirobond; BEGO Implant Systems GmbH & Co. KG, Bremen, Germany) or Locator(r) attachments, allocated randomly, were attached, and both clips and a framework were incorporated into the denture by the dental technician. The implants were loaded within 72 hours. RESULTS: During a mean observation period of 6 months (maximum 24 months, SD 0.43) eight implants in five patients were lost. Survival was 93.5% for the Locator(r) group and 89.1% for the bar group. Estimated cumulative survival after 1 year of function was 93.4% for the Locator(r) group and 87.1% for the bar group. During the observation period, 12 prosthetic complications required aftercare. No superstructure was lost or had to be remade for prosthetic reasons, but five dentures had to be removed or reworked after implant failure. Survival of the original dentures was, therefore, 95.7% for the Locator(r) group and 93.5% for the bar group. CONCLUSION: Within the limitations of this study, immediate loading of two implants in the edentulous mandible with either Locator(r) or bar attachments did hardly differ. Ease of repair and cleaning, in particular, might be arguments for choosing the single attachment system. PMID- 24215716 TI - Evidence for a stimulatory role of high doses of recombinant human follicle stimulating hormone in the treatment of male-factor infertility. AB - The efficacy of recombinant human follicle-stimulating hormone (rhFSH) in the treatment of normogonadotropic patients with male-factor infertility was assessed. Forty-five infertile men with moderate/severe oligoasthenozoospermia and normal FSH, luteinizing hormone (LH) and testosterone (T) levels were treated with high rhFSH dose (300 IU) on alternate days for >=4 months. In all, the seminal parameters, endocrine profile (FSH, LH, prolactin (PRL), total and free T and estradiol) and pregnancy rate were evaluated before, during and after rhFSH treatment. Fifteen infertile men were treated with placebo and studied in the same way, as control group. rhFSH treatment induced a marked increase in sperm count and no change in sperm motility, morphology and viability. No changes in seminal parameters were observed in the placebo group. FSH levels increased during treatment with rhFSH and not with placebo. No variations in LH, PRL, free and total T and estradiol were evidenced during treatment. A significant pregnancy rate in rhFSH versus placebo patients was also highlighted. Prolonged treatment with high rhFSH doses leads to increase sperm count and improve the spontaneous pregnancy rate in normogonadotropic infertile patients with oligoasthenozoospermia. rhFSH may represent a rational and useful tool in the treatment of male-factor infertility. PMID- 24215717 TI - Are empathic abilities learnable? Implications for social neuroscientific research from psychometric assessments. AB - Empathy is defined as an individually varying but stable personality trait. To our knowledge this notion seems questionable considering recent studies proving neuronal plasticity not only in childhood and adolescence but over the whole lifespan. We propose a model in which an individual's basic empathic abilities arising from genetic factors, brain maturation, and early attachment experiences are continually modulated by the intensity, continuity, and frequency of interpersonal socio-emotional stimulation and challenges. We assume neural processes and their underlying neural structures being modified by social and socio-emotional stimulation. Continuous social interactions should produce noticeable effects on the empathic abilities of an individual independent of age or brain maturation level. In particular, empathic abilities should be learnable and expandable beyond specific developmental windows. To elucidate this hypothesis we surveyed empathy measures of students of various professions with the help of a new instrument, the Questionnaire of Cognitive and Affective Empathy (QCAE) categorizing them into three different groups depending on their subsequent occupational fields: medical students, students of academic social professions, and a control group. Results indicate that continuous socio emotional stimulation could increase empathic abilities potentially leading to learning effects. PMID- 24215718 TI - Large-scale fabrication of nanopatterned sapphire substrates by annealing of patterned Al thin films by soft UV-nanoimprint lithography. AB - Large-scale nanopatterned sapphire substrates were fabricated by annealing of patterned Al thin films. Patterned Al thin films were obtained by soft UV nanoimprint lithography and reactive ion etching. The soft mold with 550-nm-wide lines separated by 250-nm space was composed of the toluene-diluted polydimethylsiloxane (PDMS) layer supported by the soft PDMS. Patterned Al thin films were subsequently subjected to dual-stage annealing due to the melting temperature of Al thin films (660 degrees C). The first comprised a low temperature oxidation anneal at 450 degrees C for 24 h. This was followed by a high-temperature annealing in the range of 1,000 degrees C and 1,200 degrees C for 1 h to induce growth of the underlying sapphire single crystal to consume the oxide layer. The SEM results indicate that the patterns were retained on sapphire substrates after high-temperature annealing at less than 1,200 degrees C. Finally, large-scale nanopatterned sapphire substrates were successfully fabricated by annealing of patterned Al thin films for 24 h at 450 degrees C and 1 h at 1,000 degrees C by soft UV-nanoimprint lithography. PMID- 24215719 TI - Locomotor behavior in zebrafish (Danio rerio) larvae exposed to perfluoroalkyl acids. AB - Perfluoroalkyl acids (PFAAs) are persistent organic contaminants that have been detected in wildlife, humans and the environment. Studies have shown that the toxicity of PFAAs is determined by the carbon chain length as well as the attached functional group. The locomotor activity of zebrafish larvae has become widely used for evaluation of chemicals with neurotoxic properties. In the present study the behavioral effects of seven structurally different PFAAs (i.e. TFAA, PFBA, PFOA, PFNA, PFDA, PFBS and PFOS) were evaluated in zebrafish larvae. Exposure to high concentrations of TFAA, PFNA, PFBS and PFOS resulted in distinct changes in behavioral patterns. Based on redundancy analysis, our results demonstrate three main factors affecting zebrafish larval locomotor behavior. The strongest effect on behavior was determined by the carbon chain length and the attached functional group. PFAAs with longer carbon chain length as well as PFAAs with attached sulfonic groups showed larger potential to affect locomotor behavior in zebrafish larvae. Also the concentration of the PFAAs determined the behavior responses. The results of the present study are in agreement with previous studies showing correlations between the chemical structure of PFAAs and the toxicological effects. PMID- 24215720 TI - Urinary proteomic and non-prefractionation quantitative phosphoproteomic analysis during pregnancy and non-pregnancy. AB - BACKGROUND: Progress in the fields of protein separation and identification technologies has accelerated research into biofluids proteomics for protein biomarker discovery. Urine has become an ideal and rich source of biomarkers in clinical proteomics. Here we performed a proteomic analysis of urine samples from pregnant and non-pregnant patients using gel electrophoresis and high-resolution mass spectrometry. Furthermore, we also apply a non-prefractionation quantitative phosphoproteomic approach using mTRAQ labeling to evaluate the expression of specific phosphoproteins during pregnancy comparison with non-pregnancy. RESULTS: In total, 2579 proteins (10429 unique peptides) were identified, including 1408 from the urine of pregnant volunteers and 1985 from the urine of non-pregnant volunteers. One thousand and twenty-three proteins were not reported in previous studies at the proteome level and were unique to our study. Furthermore, we obtained 237 phosphopeptides, representing 105 phosphoproteins. Among these phosphoproteins, 16 of them were found to be significantly differentially expressed, of which 14 were up-regulated and two were down-regulated in urine samples from women just before vaginal delivery. CONCLUSION: Taken together, these results offer a comprehensive urinary proteomic profile of healthy women during before and after vaginal delivery and novel information on the phosphoproteins that are differentially regulated during the maintenance of normal pregnancy. Our results may provide a better understanding of the mechanisms of pregnancy maintenance, potentially leading to the development of biomarker-based sensitive assays for understanding pregnancy. PMID- 24215721 TI - Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review. AB - OBJECTIVE: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. METHOD: Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). RESULTS: Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. CONCLUSION: Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. PMID- 24215722 TI - An integrated microfluidic device utilizing vancomycin conjugated magnetic beads and nanogold-labeled specific nucleotide probes for rapid pathogen diagnosis. AB - A PCR-free assay for rapid pathogen diagnosis was implemented on an integrated microfluidic system in this study. Vancomycin-conjugated magnetic beads were used to capture multiple strains of bacteria and nucleotide probes labeled gold nanoparticles were used to specify and detect a specific strain by hybridization induced color change. The assay was entirely automated within an integrated microfluidic device that was composed of suction-type micropumps, microvalves, microchannels, and microchambers that fabricated by microfluidic technology. Multiple strains of bacteria could be captured simultaneously by vancomycin conjugated magnetic beads, with capturing efficiency exceeding 80%. Subsequently, sensitive and strain-specific detection against target bacteria could be achieved by using nanogold labeled specific nucleotide probes. The limit of detection of 10(2)CFU bacteria was achieved. Importantly, nucleic acid amplification was not involved in the diagnostic procedures; the entire analytic process required only 25min. The developed platform may provide a promising tool for rapid diagnosis of bacterial infections. FROM THE CLINICAL EDITOR: In this novel study, a PCR-free pathogen detection method is demonstrated. After vancomycin-conjugated magnetic beads captured bacteria, nucleotide probes-labeled gold nanoparticles were employed to specify and detect specific strains via hybridization-induced color change. Multiple strains of bacteria could be captured simultaneously with an efficiency exceeding 80%, enabling the detection of as low as 10(2) CFU of bacteria. PMID- 24215723 TI - Repair of giant subcostal hernia using porcine acellular dermal matrix (StratticeTM) with bone anchors and pedicled omental flap coverage: a case report. AB - INTRODUCTION: Giant abdominal wall hernias represent a major challenge to the hernia surgeon in practice today. Of the common abdominal wall hernias, those located in the subcostal region are among the most difficult to repair, and have historically been plagued by higher recurrence rates than other locations, such as the midline. No technique has been identified as the clearly superior choice for hernias of this type. CASE PRESENTATION: We report a successful repair of a giant, multiply recurrent subcostal hernia with loss of domain in a 45-year-old obese Caucasian man. This was accomplished in a novel fashion, using a porcine acellular dermal matrix (StratticeTM) as the floor of the repair, which was fixed to the costal margin using orthopedic bone anchors (MitekTM), then covered with a pedicled omental flap to eliminate dead space and facilitate a more rapid revascularization of the porcine acellular dermal matrix implant. CONCLUSIONS: This case emphasizes the need for a thorough understanding of the challenges of the specific type of hernia defect encountered, as well as knowledge of any available techniques that may be adjunctively employed to enhance the chances of achieving a successful result. PMID- 24215725 TI - New world of 3-D printing offers "completely new ways of thinking": Q&A with author, engineer, and 3-D printing expert Hod Lipson. AB - With stories about everything from a three-?dimensional (3-D)-printed tracheal implant used in an infant to a 3-D-printed replacement for 75% of a man?s skull, a media firestorm is swirling around this seemingly new technology, but what exactly is 3-D printing? How is it being used today, and what is its true potential in the biomedical arena? Renowned robotics engineer Hod Lipson, coauthor of Fabricated: The New World of 3D Printing [1], and director of the Creative Machines Lab at Cornell University?s Sibley School of Mechanical and Aerospace Engineering in Ithaca, New York, spent some time with IEEE Pulse in a wide-ranging conversation about the past, present, and future of 3-D printing and its implications for biomedical engineering. PMID- 24215726 TI - EMAS position statement: Fertility preservation. AB - INTRODUCTION: The increasing incidence of malignant diseases that often require gonadotoxic treatment and the tendency to become a parent later in life result in an increased need for fertility preservation. AIMS: The aim of this position statement is to provide and critically appraise evidence on available options for fertility preservation in both pre-pubertal and post-pubertal men and women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Fertility preservation should be a priority when treating children or adults of reproductive age with agents that may have hazardous effects on the reproductive system. Gonadotoxicity should be kept at a minimum. If gonadotoxic treatment has to be used, methods of fertility preservation should be discussed, as early as possible. PMID- 24215727 TI - Nutrition and breast cancer. AB - Breast cancer incidence is rising worldwide with an increase in aggressive neoplasias in young women. Suspected factors responsible for the global increase include lifestyle changes, notably diet. Currently accepted risk factors directly linked to diet are greater body weight and alcohol consumption. Weight gain in adulthood is associated with increased risk of breast cancer in post-menopausal women, suggesting that weight gain before and around menopausal age may be determinant for breast cancer development among postmenopausal women. Numerous studies also show an impact of specific diets and nutrients - fatty acids, carbohydrates, vitamins B, D, carotenoids, phytoestrogens, fiber - on breast cancer risk, and evidence supports a mechanistic basis for an influence of specific nutrients. However, these studies are plagued with conflicting results. In this review, a new examination of the relationship between nutrition and breast cancer is proposed in light of recent epidemiological studies. Successful development of breast cancer prevention strategies will require identification of biological markers of dietary exposure, and to coordinate worldwide research to discern the effects of diet. PMID- 24215728 TI - Re. 'Left renal vein division during open surgery of abdominal aortic disease: a propensity score-matched case-control study'. PMID- 24215724 TI - Proteinase-activated receptors (PARs) - focus on receptor-receptor-interactions and their physiological and pathophysiological impact. AB - Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino terminal "tethered ligand" domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor trafficking processes that result in multiple physiological effects.In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID- 24215729 TI - A novel nickel-chelated surfactant for affinity-based aqueous two-phase micellar extraction of histidine-rich protein. AB - Aqueous two-phase micellar systems (ATPMSs) composed of nonionic surfactants are considered promising for the separation and purification of proteins. To improve the specificity of ATPMSs, a novel nickel-chelated surfactant was prepared by successive modifications of Triton X-114 (TX). Characterizations by Fourier transformation infrared spectroscopy demonstrated the successful synthesis of the nickel-chelated surfactant (TX-Ni). The cloud point, critical micelle concentration (CMC), molecular interaction parameter and micelle size were measured for the mixed surfactant system of TX-Ni and TX to achieve a full understanding of their aggregation behaviors. The results showed that mixed micelles were formed, and the cloud point increased with the mole fraction of TX Ni because TX-Ni had a more hydrophilic head group than TX. Moreover, the reduction of micelle size revealed by light scattering experiments indicated that the insertion of TX-Ni inhibited the micellar growth due to the increased steric and electrostatic repulsion. Finally, the efficiency of TX-Ni as an affinity surfactant was demonstrated by the affinity partitioning of histidine-tagged enhanced green fluorescent protein with an over 20-fold increase of the partition coefficient (from 0.60 to 12.42). This affinity-based ATPMS is thus considered promising for providing a versatile platform for the separation of histidine-rich proteins. PMID- 24215730 TI - Comparing three CPR feedback devices and standard BLS in a single rescuer scenario: a randomised simulation study. AB - BACKGROUND: Efficiently performed basic life support (BLS) after cardiac arrest is proven to be effective. However, cardiopulmonary resuscitation (CPR) is strenuous and rescuers' performance declines rapidly over time. Audio-visual feedback devices reporting CPR quality may prevent this decline. We aimed to investigate the effect of various CPR feedback devices on CPR quality. METHODS: In this open, prospective, randomised, controlled trial we compared three CPR feedback devices (PocketCPR, CPRmeter, iPhone app PocketCPR) with standard BLS without feedback in a simulated scenario. 240 trained medical students performed single rescuer BLS on a manikin for 8min. Effective compression (compressions with correct depth, pressure point and sufficient decompression) as well as compression rate, flow time fraction and ventilation parameters were compared between the four groups. RESULTS: Study participants using the PocketCPR performed 17+/-19% effective compressions compared to 32+/-28% with CPRmeter, 25+/-27% with the iPhone app PocketCPR, and 35+/-30% applying standard BLS (PocketCPR vs. CPRmeter p=0.007, PocketCPR vs. standard BLS p=0.001, others: ns). PocketCPR and CPRmeter prevented a decline in effective compression over time, but overall performance in the PocketCPR group was considerably inferior to standard BLS. Compression depth and rate were within the range recommended in the guidelines in all groups. CONCLUSION: While we found differences between the investigated CPR feedback devices, overall BLS quality was suboptimal in all groups. Surprisingly, effective compression was not improved by any CPR feedback device compared to standard BLS. All feedback devices caused substantial delay in starting CPR, which may worsen outcome. PMID- 24215731 TI - Applying lessons from commercial aviation safety and operations to resuscitation. AB - Both commercial aviation and resuscitation are complex activities in which team members must respond to unexpected emergencies in a consistent, high quality manner. Lives are at stake in both activities and the two disciplines have similar leadership structures, standard setting processes, training methods, and operational tools. Commercial aviation crews operate with remarkable consistency and safety, while resuscitation team performance and outcomes are highly variable. This commentary provides the perspective of two physician-pilots showing how commercial aviation training, operations, and safety principles can be adapted to resuscitation team training and performance. PMID- 24215732 TI - Lateral boundary mechanosensing by adherent cells in a collagen gel system. AB - Cell adhesion responses to in-depth physical properties such as substrate roughness and topography are well described but little is known about the influence of lateral physical cues such as tissue boundaries on the function of adherent cells. Accordingly, we developed a model system to examine remote cell sensing of lateral boundaries. The model employs floating thin collagen gels supported by rigid grids of varying widths. The dynamics, lengths, and numbers of cell extensions were regulated by grid opening size, which in turn determined the distance of cells from rigid physical boundaries. In smaller grids (200 MUm and 500 MUm wide), cell-induced deformation fields extended to, and were resisted by, the grid boundaries. However, in larger grids (1700 MUm wide), the deformation field did not extend to the grid boundaries, which strongly affected the mean length and number of cell extensions (~60% reduction). The generation of cell extensions in collagen gels required expression of the beta1 integrin, focal adhesion kinase and actomyosin activity. We conclude that the presence of physical boundaries interrupts the process of cell-mediated collagen compaction and fiber alignment in the collagen matrix and enhances the formation of cell extensions. This new cell culture platform provides a geometry that more closely approximates the native basement membrane and will help to elucidate the roles of cell extensions and lateral mechanosensing on extracellular matrix remodeling by invasion and degradation. PMID- 24215733 TI - Effects of bound versus soluble pentosan polysulphate in PEG/HA-based hydrogels tailored for intervertebral disc regeneration. AB - Previous reports in the literature investigating chondrogenesis in mesenchymal progenitor cell (MPC) cultures have confirmed the chondro-inductive potential of pentosan polysulphate (PPS), a highly sulphated semi-synthetic polysaccharide, when added as a soluble component to culture media under standard aggregate-assay conditions or to poly(ethylene glycol)/hyaluronic acid (PEG/HA)-based hydrogels, even in the absence of inductive factors (e.g. TGFbeta). In this present study, we aimed to assess whether a 'bound' PPS would have greater activity and availability over a soluble PPS, as a media additive or when incorporated into PEG/HA-based hydrogels. We achieved this by covalently pre-binding the PPS to the HA component of the gel (forming a new molecule, HA-PPS). We firstly investigated the activity of HA-PPS compared to free PPS, when added as a soluble factor to culture media. Cell proliferation, as determined by CCK8 and EdU assay, was decreased in the presence of either bound or free PPS whilst chondrogenic differentiation, as determined by DMMB assay and histology, was enhanced. In all cases, the effect of the bound PPS (HA-PPS) was more potent than that of the unbound form. These results alone suggest wider applications for this new molecule, either as a culture supplement or as a coating for scaffolds targeted at chondrogenic differentiation or maturation. We then investigated the incorporation of HA-PPS into a PEG/HA-based hydrogel system, by simply substituting some of the HA for HA-PPS. Rheological testing confirmed that incorporation of either HA-PPS or PPS did not significantly affect gelation kinetics, final hydrogel modulus or degradation rate but had a small, but significant, effect on swelling. When encapsulated in the hydrogels, MPCs retained good viability and rapidly adopted a rounded morphology. Histological analysis of both GAG and collagen deposition after 21 days showed that the incorporation of the bound-PPS into the hydrogel resulted in increased matrix formation when compared to the addition of soluble PPS to the hydrogel, or the hydrogel alone. We believe that this new generation injectable, degradable hydrogel, incorporating now a covalently bound-PPS, when combined with MPCs, has the potential to assist cartilage regeneration in a multitude of therapeutic targets, including for intervertebral disc (IVD) degeneration. PMID- 24215734 TI - Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering. AB - The fabrication of an instructive bioabsorbable scaffold is one of the main goals for tissue engineering applications. In this regard, genipin cross-linked gelatin scaffolds, produced by electrospinning, were tested as a platform to include decellularized rat brain extracellular matrix as an active agent to provide fundamental biochemical cues to the seeded cells. This approach is expected to furnish a suitable natural-based polymeric scaffold with sufficient temporal stability to support cell attachment and spreading, also providing tissue specific signals that can contribute to the expression of the requested cellular phenotype. We first demonstrated the effectiveness of the proposed decellularization protocol and the cytocompatibility of the resulting brain matrix. Then, the in vitro biological assays of the conditioned electrospun scaffolds, using rat allogeneic mesenchymal stromal cells, confirmed their biocompatibility and showed a differentiative potential in presence of just 1% w/w decellularized rat brain extracellular matrix. PMID- 24215735 TI - Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs. AB - Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. PMID- 24215736 TI - Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery. AB - The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 MUm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system. PMID- 24215737 TI - Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety. AB - The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161. PMID- 24215738 TI - Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women. AB - AIM: In this study we investigate in in vitro myometrial tissue samples of pregnant women: (a) the effects of proton pomp inhibitors (PPIs) (omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole) on spontaneous contractions; (b) the muscle-relaxant efficacy of the most active PPI considered (pantoprazole) in comparison with that of other known tocolytics (nifedipine, atosiban, MgSO4, isoxsuprine); (c) the effect of pantoprazole on contractions induced by calcium (Ca(++)), KCl, oxytocin and prostaglandin (PGE2); (d) the possible mediators of pantoprazole relaxant effect. METHODS: Organ bath studies were performed on myometrial tissue samples (40*10*10 mm) from pregnant women (38 42 weeks of gestational age) undergoing elective caesarian section. RESULTS: All the PPIs studied reduce the spontaneous contraction of the myometrial smooth muscle. Pantoprazole is the most effective and most potent inhibitor among those analyzed. Pantoprazole also reduces the contractions induced by Ca(++), KCl, oxytocin and PGE2. Neither NO, nor PGs, or the activation of Ca(++)-dependent K(+) currents mediate the muscle-relaxant effect of this PPI. CONCLUSION: These data, together with the fact that PPIs almost do not present side effects, suggest that these drugs can offer new therapeutic strategies for preterm delivery. Undoubtedly, further investigations and clinical studies are necessary before adding PPIs to the list of drugs available for the treatment of preterm delivery. PMID- 24215739 TI - Th9 cells, new players in adaptive immunity. AB - Upon antigen-specific stimulation, naive CD4+ T cells have the potential to differentiate into various T helper (Th) cell subsets. Earlier models of Th cell differentiation focused on IFN-gamma-producing Th1 cells and IL-4-secreting Th2 cells. The discovery of additional CD4+ Th cell subsets has extended our understanding of Th cell differentiation beyond this dichotomy. Among these is the recently described Th9 cell subset, which preferentially produces interleukin (IL)-9. Here, we review the latest developments in Th9 cell development and differentiation, focusing on contributing environmental signals, and discuss potential physiological and pathophysiological functions of these cells. We describe the challenges inherent to unambiguously defining roles for Th9 cells using the available experimental animal models, and suggest new experimental models to address these concerns. PMID- 24215740 TI - The changing of the guards: can family doctors contain worker absenteeism? AB - Using administrative data from Norway, we examine the extent to which family doctors influence their clients' propensity to claim sick-pay. The analysis exploits exogenous switches of family doctors occurring when physicians quit, retire, or for other reasons sell their patient lists. We find that family doctors have significant influence on their clients' absence behavior, particularly on absence duration. Their influence is stronger in geographical areas with weaker competition between physicians. We conclude that it is possible for family doctors to contain sick-pay expenditures to some extent, and that there is a considerable variation in the way they perform this task. PMID- 24215741 TI - Using Cone Beam Computed Tomography Angle for Predicting the Outcome of Horizontal Bone Augmentation. AB - BACKGROUND: The aim of this study was to assess the influence of ridge morphology on the amount of horizontal bone augmentation achieved with the sandwich bone augmentation (SBA) technique in the reconstruction of buccal dehiscence defects on dental implants. METHODS: Cone beam computed tomography (CBCT) was used to assess bone width changes in 26 patients who participated in a randomized controlled trial conducted in 2008 to 2011. The amount of horizontal bone gain was evaluated at four different levels (3, 6, 9, and 12 mm apical to the alveolar crest) and three different time points (T1: baseline, T2: at time of graft placement, and T3: 6 months later). Different morphological characteristics of the alveolar ridge were also evaluated to determine their influence on horizontal bone augmentation. A total of 78 CBCT scans were assessed. RESULTS: Comparison of the changes in ridge morphology at all measurement locations showed an overall ridge width gain of 2.30 +/- 2.20 mm after 6 months. The use of membranes and the angulation of the concavity played a role in influencing the outcomes of the SBA technique. Critical crest angulation (CA) is 150 degrees for bone gain at 9 mm apical to the crest. When CA is smaller than 150 degrees , the horizontal bone gain was 4.3 +/- 2.2 mm; if CA is greater than 150 degrees , the gain was significantly lower at 1.3 +/- 1.7 mm (p = .001). CONCLUSIONS: SBA is a reliable and predictable technique to gain horizontal ridge width with simultaneous implant placement. Crest ridge angulation can be used as a tool to predict bone gain at 9 mm apical to the bone crest. PMID- 24215743 TI - Ambulatory ECG monitoring: 50 years later. PMID- 24215742 TI - Autoimmunity to citrullinated proteins and the initiation of rheumatoid arthritis. AB - Clinical manifestations of rheumatoid arthritis (RA), the second most common human autoimmune disease, are primarily focused on the joints, causing disability and requiring life-long treatment to ameliorate signs and symptoms. The etiology of RA is unknown; however, important discoveries in two areas have been made which provide hope that the causal mechanisms can be identified. First, the most severe form of this disease is associated with the presence of humoral and cellular autoimmunity to citrullinated proteins and peptides. Second, in the natural history of RA, autoimmunity to citrullinated antigens appears years before the onset of clinically apparent disease. Herein is described a model in which to consider how these two features are linked during very early disease development. PMID- 24215744 TI - The evolution of ambulatory ECG monitoring. AB - Ambulatory Holter electrocardiographic (ECG) monitoring has undergone continuous technological evolution since its invention and development in the 1950s era. With commercial introduction in 1963, there has been an evolution of Holter recorders from 1 channel to 12 channel recorders with increasingly smaller storage media, and there has evolved Holter analysis systems employing increasingly technologically advanced electronics providing a myriad of data displays. This evolution of smaller physical instruments with increasing technological capacity has characterized the development of electronics over the past 50 years. Currently the technology has been focused upon the conventional continuous 24 to 48 hour ambulatory ECG examination, and conventional extended ambulatory monitoring strategies for infrequent to rare arrhythmic events. However, the emergence of the Internet, Wi-Fi, cellular networks, and broad-band transmission has positioned these modalities at the doorway of the digital world. This has led to an adoption of more cost-effective strategies to these conventional methods of performing the examination. As a result, the emergence of the mobile smartphone coupled with this digital capacity is leading to the recent development of Holter smartphone applications. The potential of point-of-care applications utilizing the Holter smartphone and a vast array of new non-invasive sensors is evident in the not too distant future. The Holter smartphone is anticipated to contribute significantly in the future to the field of global health. PMID- 24215745 TI - Prognostic significance of ambulatory ECG monitoring for ventricular arrhythmias. AB - Ventricular arrhythmia can be detected in ambulatory ECG monitoring in individuals with or without cardiac disease, and its prognostic value varies, depending on the underlying condition. The use of continuous or intermittent ambulatory ECG monitoring can be helpful for diagnosis when there is a high pre test probability of identifying a transient arrhythmia. In addition, Holter monitoring can be used for risk stratification of patients, in the context of the prognostic value of non-sustained ventricular arrhythmias in various clinical settings, as discussed in detail. PMID- 24215746 TI - Ambulatory ECG monitoring in atrial fibrillation management. AB - Ambulatory ECG monitoring technology has rapidly evolved over the last few decades and has been shown to identify life-threatening and non-life threatening arrhythmias and provide actionable data to guide clinical decision making. Atrial fibrillation episodes can often be asymptomatic, even after catheter ablation for atrial fibrillation, creating a disconnect between symptoms and actual arrhythmia burden which may alter clinical management. In this review, we aim to provide a comprehensive overview of invasive and non-invasive ECG monitoring strategies in patients with atrial fibrillation, with a special focus on the diagnosis of atrial fibrillation, and on follow-up of patients after catheter ablation for atrial fibrillation ablation. PMID- 24215747 TI - Heart rate variability in risk stratification of cardiac patients. AB - Heart rate (HR) variability has been extensively studied in cardiac patients, especially in patients surviving an acute myocardial infarction (AMI) and also in patients with congestive heart failure (CHF) or left ventricular (LV) dysfunction. The majority of studies have shown that patients with reduced or abnormal HR variability have an increased risk of mortality within a few years after an AMI or after a diagnosis of CHF/LV dysfunction. Various measures of HR dynamics, such as time-domain, spectral, and non-linear measures of HR variability have been used in risk stratification. The prognostic power of various measures, except of those reflecting rapid R-R interval oscillations, has been almost identical, albeit some non-linear HR variability measures, such as short-term fractal scaling exponent have provided somewhat better prognostic information than the others. Abnormal HR variability predicts both sudden and non sudden cardiac death. Because of remodeling of the arrhythmia substrate after AMI, early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events. Future randomized trials using HR variability/turbulence as one of the pre defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of cardiac patients. PMID- 24215748 TI - Heart rate turbulence. AB - Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. PMID- 24215749 TI - Ambulatory ECG-based T-wave alternans monitoring for risk assessment and guiding medical therapy: mechanisms and clinical applications. AB - Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy. PMID- 24215750 TI - QT Variability Index. AB - The QT Variability Index (QTVI) is a non-invasive measure of repolarization lability that has been applied to a wide variety of subjects with cardiovascular disease. It is a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of autonomic nervous system tone. The approach assesses beat-to-beat variability in the duration of the QT and U wave in conventional surface electrocardiographic recordings, as well as determines the heart rate variability (HRV) from the same recording. As opposed to T wave alternans, QTVI assesses variance in repolarization at all frequencies. Nineteen studies have published data on QTVI in healthy individuals, while 20 have evaluated its performance in cohorts with cardiovascular disease. Six studies have assessed the utility of QTVI in predicting VT/VF, cardiac arrest, or cardiovascular death. A prospective study utilizing QTVI to determine therapy allocation has not been performed, and therefore the final determination of the value of the metric awaits definitive exploration. PMID- 24215752 TI - ECG monitoring in syncope. AB - Electrocardiographic (ECG) monitoring is a well-established procedure in the work up of patients with syncope or for diagnosing arrhythmias. The investigation of syncope remains, however, challenging and physicians have an increasing armamentarium of diagnostic tools available and with advances in technology the role of these tools has to be continuously evaluated. The gold standard for the diagnosis of syncope is a symptom-ECG correlation, and while many studies have investigated the use and indications of both short-term and long-term monitoring; there is still some uncertainty in their clinical utility and practical approach. The use of ECG monitoring and other diagnostic tools is often subject to a "shot gun approach" rather than a strict guideline algorithm. A systematic approach and selection of ECG monitoring tools helps permit an effective usage of the limited health care resources available for the management of unexplained syncope. In this review we aim to focus and clarify the role of short-term (Holter and external loop recorders) and long-term (implantable loop recorders) ECG monitoring in the diagnosis and management of patients with unexplained syncope. PMID- 24215751 TI - The clinical significance of continuous ECG (ambulatory ECG or Holter) monitoring of the ST-segment to evaluate ischemia: a review. AB - Silent ischemia is a common manifestation of coronary artery disease (CAD). Continuous ECG (cECG) monitoring is an effective tool for assessing the frequency and duration of silent ischemic episodes for patients with CAD and for risk stratifying asymptomatic patients or those after an acute coronary syndrome by identifying those at increased risk for future cardiovascular events or death. cECG also allows monitoring of the effectiveness of therapy in patients with CAD. Treatment strategies targeted toward the elimination of silent ischemia have shown that revascularization was better than medical therapy in eliminating silent ischemia, but large scale, prospective studies targeting silent ischemia as a treatment endpoint are still lacking. Future research is warranted to study the effects of newer medical agents or the selected use of revascularization in those patients with persistent silent ischemia despite current medical regiments. PMID- 24215753 TI - Holter in monitoring of cardiac pacing. AB - The Holter function of implanted devices will record events with characteristics meeting criteria determined by the manufacturer or programmed by the physician. It does not show a continuous ECG. It is reliable, provided the basic functions of the device are operating correctly. This is an ideal tool for assessing the electrophysiologic profile of heart disease patients with implants and to assess the efficacy of various treatments (anti-arrhythmic drugs, ablation procedures). Combined with telemedicine technology, it can provide early alerts to the physician about deterioration in the rhythmic or hemodynamic status of their patients and thus prevent complications that would otherwise have led to costly hospitalizations. It is a very reliable tool to assess ICD function (diagnostic capabilities by the discrimination algorithms and efficacy of the delivered therapies). The technology will evolve and offer extended data in the future, such as sensor information or repolarization data (ST segment, QT duration, variability, &c.). PMID- 24215754 TI - ECG patch monitors for assessment of cardiac rhythm abnormalities. AB - The primary goal of long-term monitoring is the improvement of diagnostic yield. Despite the clear utility of Holter monitoring in clinical cardiology, issues of relatively low diagnostic yield, cost and inconvenience have motivated the development of ultra-portable devices referred to as ECG patch monitors. Although the "gold standard" for assessing cardiac rhythm abnormalities remains a 12-lead Holter, there is an increasing interest in portable monitoring devices that provide the opportunity for evaluating cardiac rhythm in real-world environments such as the workplace or home. To facilitate patient acceptance these monitors underwent a radical miniaturization and redesign to include wireless communication, water proofing and a patch carrier for attaching devices directly to the skin. We review recent developments in the field of "patch" devices primarily designed for very long-term monitoring of cardiac arrhythmic events. As the body of supporting clinical validation data grows, these devices hold promise for a variety of cardiac monitoring applications. From a clinical and research standpoint, the capacity to obtain longitudinal cardiac activity data by patch devices may have significant implications for device selection, monitoring duration, and care pathways for arrhythmia evaluation and atrial fibrillation surveillance. From a research standpoint, the new devices may allow for the development of novel diagnostic algorithms with the goal of finding patterns and correlations with exercise and drug regimens. PMID- 24215755 TI - Modifications of mesenteric adipose tissue during moderate experimental colitis in mice. AB - AIMS: Adipose tissue secretes various proteins referred to as adipokines, being involved in inflammation. It was recognized that mesenteric adipose tissue (MAT) is altered by inflammation, and pathologies such as inflammatory bowel disease (IBD). The aim of this study was to investigate the alterations of the mesenteric adipose tissue in two experimental colitis models in mice adapted to obtain moderate colonic inflammation. MAIN METHODS: Colonic inflammation was obtained using two models, either DSS dissolved in drinking water or intra-colonic instillation of DNBS. The expression of adipokines (leptin and adiponectin) and inflammatory markers (IL-6, MCP-1, F4/80) was studied by qRT-PCR in the MAT of treated and control mice. KEY FINDINGS: Observations of the colon and IL-6 plasma level determination demonstrated that DNBS treatment led to stronger inflammation. Colitis induced a decrease of mRNA encoding to leptin and adiponectin in MAT. In contrast, colonic inflammation led to an increase of mRNA encoding to IL-6, MCP-1 and F4/80, a specific marker of macrophages. SIGNIFICANCE: The mesenteric adipose tissue, in two models of moderate colitis, shows a loss of adipose profile and a strong increase of inflammatory pattern, close to the observations made in MAT of IBD patients. These data suggest that these pro-inflammatory modifications of MAT have to be taken into account in the pathophysiology of IBD. PMID- 24215756 TI - The changing paradigm in EUS-guided tissue acquisition. AB - The diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration is strongly dependent on the availability of an onsite cytopathologist. The diagnosis of some rare tumors may require ancillary testing for which a histologic core biopsy is required. There is increasing interest in evaluating core tissue for molecular markers that may serve as prognostic predictors and targets for focused chemotherapy in patients with cancer. If core tissue can be procured efficiently and reliably at endoscopic ultrasound, this will eliminate the need for an onsite cytopathologist, accurately diagnose tumors that are occasionally missed by fine-needle aspiration cytology, and enable the assessment for molecular markers. PMID- 24215757 TI - Beyond cytology: why and when does the oncologist require core tissue? AB - There are 2 main reasons why oncologists may require additional tissue and a histologic section in addition to cytopathology from FNA specimens: improved diagnostic accuracy and molecular characterization of tumors. Rather than mutually exclusive diagnostic procedures, EUS-FNA and EUS-CNB must be viewed as supplementary techniques and both approaches should be incorporated as essential tools in the current endoscopic armamentarium. PMID- 24215758 TI - Definitions in tissue acquisition: core biopsy, cell block, and beyond. AB - This article identifies key fundamentals of tissue acquisition, sample preparation, and staining. It defines the understanding of different aspects of sample preparations, such as types of smear-preparation techniques, touch preparations, types of fixative, and newer technologies such as liquid-based preparations. PMID- 24215759 TI - How can an endosonographer assess for diagnostic sufficiency and options for handling the endoscopic ultrasound-guided fine-needle aspiration specimen and ancillary studies. AB - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become well established as a minimally invasive technique in diagnosing and staging various gastrointestinal, pancreaticobiliary, and retroperitoneal malignancies. The diagnostic accuracy of this procedure is significantly enhanced by the presence of on-site cytopathology. However, in many EUS centers, cytopathology is not readily available for on-site evaluation. This article is intended to assist the independent endosonographer in the assessment of diagnostic sufficiency and in specimen handling. PMID- 24215760 TI - Endoscopic ultrasound-guided fine-needle aspiration needles: which one and in what situation? AB - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is increasingly used as a diagnostic and therapeutic tool for pancreatic and other gastrointestinal disorders. Several factors affect the outcome of EUS-FNA, one of which is needle size. The decision to use a specific needle depends on factors including location, consistency, and type of the lesion; presence of onsite cytopathologist; and need for additional tissue procurement for histology. This review provides a balanced perspective on the use of different needle sizes available, highlighting the differences among them and potential niche applications of each to maximize diagnostic yield of EUS-FNA. PMID- 24215761 TI - Techniques for EUS-guided FNA cytology. AB - This article addresses the technique of endoscopic ultrasound-guided fine-needle aspiration of solid lesions to obtain cytologic specimens. The technique can be broken down into a sequence of steps. The ultimate goal is to maximize the likelihood of obtaining adequate tissue for diagnostic purposes. This requires a technique that ensures that the needle can be moved inside the lesion, under ultrasound guidance, as widely as possible, as easily as possible, and safely. The other variables such as suction, needle type, and stylet use are of secondary importance. PMID- 24215762 TI - Techniques for endoscopic ultrasound-guided fine-needle biopsy. AB - Although endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the method of choice to obtain samples to reach definitive diagnosis of lesions of the gastrointestinal tract and of adjacent organs, it cannot fully characterize certain neoplasms. The lack of cytology expertise has hindered the dissemination of EUS, limiting its widespread use. The obtainment of a tissue specimen through EUS fine-needle biopsy (EUS-FNB) may overcome the limitations of EUS-FNA. EUS-FNB is expected to move the practice of EUS from cytology to histology, expanding the use of EUS and facilitating targeted therapies and monitoring of treatment response in a more biologically driven manner. PMID- 24215763 TI - Tips to overcome technical challenges in EUS-guided tissue acquisition. AB - The diagnostic yield of EUS-FNA depends on several factors, such as the experience of the endosonographer, the characteristics of the lesion, the clinical status of the patient, the size and type of needles, the methods of specimen preparation, as well as cytopathologist expertise. The endosonographic technique can be improved when several tips and tricks useful to overcome challenges of FNA are known. Technical challenges of FNA are related to the characteristics of the lesion and its surroundings, sonographic imaging, and limitations related to the needle. Several tips and tricks necessary to overcome them are presented in this review. PMID- 24215764 TI - Pitfalls in EUS FNA. AB - Although endoscopic ultrasound (EUS) fine-needle aspiration (FNA) is a safe and accurate procedure, the diagnostic yield varies. Factors contributing to the diagnostic accuracy of EUS FNA include endosonographer and cytopathologist experience, EUS image recognition, accurate FNA targeting of the lesion, proper specimen collection and handling, use of ancillary techniques, and accurate cytologic interpretation. Errors in performance or judgment made before, during, or after the procedure may affect the results of the EUS FNA. The authors discuss the potential pitfalls of EUS FNA and methods to avoid their occurrence to optimize the diagnostic yield, efficiency, and safety of the procedure. PMID- 24215765 TI - Future directions in EUS-guided tissue acquisition. AB - Endoscopic ultrasound fine-needle aspiration is considered the technique of choice for acquisition of tissue in and around the digestive tract. The emergence of selective, targeted therapies, directed toward a particular molecular characteristic of an individual patient's tumor is driving the need for biomarker identification and testing in several cancer types. The technique needs improvement to provide more material, in fewer passes, with more flexible, sharp, and clearly echovisible needles, and with a similar safety. Another trend is the avoidance of tissue acquisition, or a more targeted puncture with the help of ancillary techniques, such as optical biopsies with needle-based confocal laser endomicroscopy, contrast-enhanced ultrasonography, and elastography. PMID- 24215766 TI - New methods to obtain better tissue samples with EUS-guided FNA. PMID- 24215767 TI - Preface: EUS-guided tissue acquisition. PMID- 24215768 TI - A novel osmotic pressure control fed-batch fermentation strategy for improvement of erythritol production by Yarrowia lipolytica from glycerol. AB - The effect of osmotic pressure on erythritol and mannitol production by an osmophilic yeast strain of Yarrowia lipolytica CICC 1675 using glycerol as the sole carbon source was investigated. Appropriately high osmotic pressure was found to enhance erythritol production and inhibit mannitol formation. A novel two-stage osmotic pressure control fed-batch strategy based on the kinetic analysis was developed for higher erythritol yield and productivity. During the first 96 h, the osmotic pressure was maintained at 4.25 osmol/kg by feeding glycerol to reduce the inhibition of cell growth. After 132 h, the osmotic pressure was controlled at 4.94 osmol/kg to maintain a high dp(ery)/dt. Maximum erythritol yield of 194.3g/L was obtained with 0.95 g/L/h productivity, which were 25.7% and 2.2%, respectively, improvement over the best results in one-stage fed-batch fermentation. This is the first report that a novel osmotic pressure control fed-batch strategy significantly enhanced erythritol production. PMID- 24215769 TI - A novel kinetic model for polysaccharide dissolution during atmospheric acetic acid pretreatment of sugarcane bagasse. AB - Acetic acid (AcH) pretreatment of sugarcane bagasse with the catalysis of sulfuric acid (SA) could greatly enhance the enzymatic digestibility of cellulose. However, polysaccharide dissolution happened inevitably during the pretreatment. It was found that the simplest model, which assumes that the total polysaccharides were reactive to be dissolved, could not well describe the kinetic behavior of polysaccharide dissolution. A novel pseudo-homogenous kinetic model was thus developed by introducing a parameter termed as "potential dissolution degree" (delta(d)) based on the multilayered structure of cell wall. It was found that solid xylan and glucan dissolutions were a first-order reaction with respect to the dissolvable fraction. Due to the delignification action of AcH, polysaccharide dissolutions were enhanced in AcH media compared with those in aqueous system. Acetylizations of cellulose and sugars were also observed, and AcH concentration showed a significant influence on the degree of acetylization. PMID- 24215770 TI - The re-use of Waste-Activated Sludge as part of a "zero-sludge" strategy for wastewater treatments in the pulp and paper industry. AB - The possibility of introducing the thermo-alkali hydrolysis of Waste-Activated Sludge (WAS) was investigated, in order to enable the use of its solid residue as a raw material in cardboard production and the use of its liquid portion for anaerobic digestion in an UASB reactor. The evaluation of the hydrolysis at pH>12 and T=70 degrees C showed that the microbe cells were disrupted with more than 90% efficiency in less than 2h. The solid portion was hygienised, therefore making it possible to integrate it into the cardboard production as a raw material for less demanding cardboards. Up to 6% addition of the liquid portion of hydrolysed WAS to wastewater decreased the specific biogas production in a pilot-scale UASB from 0.236 to 0.212 m(3)/kg(COD), while the efficiency of the COD removal decreased from 80.4% to 76.5%. These values still guarantee an adequate treatment of the wastewater and an increased biogas production by 16%. PMID- 24215772 TI - High-performance solid-state supercapacitors based on graphene-ZnO hybrid nanocomposites. AB - In this paper, we report a facile low-cost synthesis of the graphene-ZnO hybrid nanocomposites for solid-state supercapacitors. Structural analysis revealed a homogeneous distribution of ZnO nanorods that are inserted in graphene nanosheets, forming a sandwiched architecture. The material exhibited a high specific capacitance of 156 F g-1 at a scan rate of 5 mV.s-1. The fabricated solid-state supercapacitor device using these graphene-ZnO hybrid nanocomposites exhibits good supercapacitive performance and long-term cycle stability. The improved supercapacitance property of these materials could be ascribed to the increased conductivity of ZnO and better utilization of graphene. These results demonstrate the potential of the graphene-ZnO hybrid nanocomposites as an electrode in high-performance supercapacitors. PMID- 24215771 TI - Microbial community composition of a down-flow hanging sponge (DHS) reactor combined with an up-flow anaerobic sludge blanket (UASB) reactor for the treatment of municipal sewage. AB - The microbial community composition of a down-flow hanging sponge (DHS) reactor in an up-flow anaerobic sludge blanket (UASB)-DHS system used for the treatment of municipal sewage was investigated. The clone libraries showed marked differences in microbial community composition at different reactor heights and in different seasons. The dominant phylotypes residing in the upper part of the reactor were likely responsible for removing organic matters because a significant reduction in organic matter in the upper part was observed. Quantification of the amoA genes revealed that the proportions of ammonia oxidizing bacteria (AOB) varied along the vertical length of the reactor, with more AOB colonizing the middle and lower parts of the reactor than the top of the reactor. The findings indicated that sewage treatment was achieved by a separation of microbial habitats responsible for organic matter removal and nitrification in the DHS reactor. PMID- 24215773 TI - Methodology and interpretation of acute tryptophan depletion studies. PMID- 24215775 TI - Technology-facilitated depression care management among predominantly Latino diabetes patients within a public safety net care system: comparative effectiveness trial design. AB - Health disparities in minority populations are well recognized. Hispanics and Latinos constitute the largest ethnic minority group in the United States; a significant proportion receives their care via a safety net. The prevalence of diabetes mellitus and comorbid depression is high among this group, but the uptake of evidence-based collaborative depression care management has been suboptimal. The study design and baseline characteristics of the enrolled sample in the Diabetes-Depression Care-management Adoption Trial (DCAT) establishes a quasi-experimental comparative effectiveness research clinical trial aimed at accelerating the adoption of collaborative depression care in safety net clinics. The study was conducted in collaboration with the Los Angeles County Department of Health Services at eight county-operated clinics. DCAT has enrolled 1406 low income, predominantly Hispanic/Latino patients with diabetes to test a translational model of depression care management. This three-group study compares usual care with a collaborative care team support model and a technology facilitated depression care model that provides automated telephonic depression screening and monitoring tailored to patient conditions and preferences. Call results are integrated into a diabetes disease management registry that delivers provider notifications, generates tasks, and issues critical alerts. All subjects receive comprehensive assessments at baseline, 6, 12, and 18 months by independent English-Spanish bilingual interviewers. Study outcomes include depression outcomes, treatment adherence, satisfaction, acceptance of assessment and monitoring technology, social and economic stress reduction, diabetes self care management, health care utilization, and care management model cost and cost effectiveness comparisons. DCAT's goal is to optimize depression screening, treatment, follow-up, outcomes, and cost savings to reduce health disparities. PMID- 24215774 TI - Design and implementation of a randomized controlled social and mobile weight loss trial for young adults (project SMART). AB - PURPOSE: To describe the theoretical rationale, intervention design, and clinical trial of a two-year weight control intervention for young adults deployed via social and mobile media. METHODS: A total of 404 overweight or obese college students from three Southern California universities (M(age) = 22( +/- 4) years; M(BMI) = 29( +/- 2.8); 70% female) were randomized to participate in the intervention or to receive an informational web-based weight loss program. The intervention is based on behavioral theory and integrates intervention elements across multiple touch points, including Facebook, text messaging, smartphone applications, blogs, and e-mail. Participants are encouraged to seek social support among their friends, self-monitor their weight weekly, post their health behaviors on Facebook, and e-mail their weight loss questions/concerns to a health coach. The intervention is adaptive because new theory-driven and iteratively tailored intervention elements are developed and released over the course of the two-year intervention in response to patterns of use and user feedback. Measures of body mass index, waist circumference, diet, physical activity, sedentary behavior, weight management practices, smoking, alcohol, sleep, body image, self-esteem, and depression occur at 6, 12, 18, and 24 months. Currently, all participants have been recruited, and all are in the final year of the trial. CONCLUSION: Theory-driven, evidence-based strategies for physical activity, sedentary behavior, and dietary intake can be embedded in an intervention using social and mobile technologies to promote healthy weight related behaviors in young adults. PMID- 24215776 TI - Challenges and prospects for dengue and malaria control in Thailand, Southeast Asia. AB - Despite significant advances in the search for potential dengue vaccines and new therapeutic schemes for malaria, the control of these diseases remains difficult. In Thailand, malaria incidence is falling whereas that of dengue is rising, with an increase in the proportion of reported severe cases. In the absence of antiviral therapeutic options for acute dengue, appropriate case management reduces mortality. However, the interruption of transmission still relies on vector control measures that are currently insufficient to curtail the cycle of epidemics. Drug resistance in malaria parasites is increasing, compromising malaria control and elimination. Deficiencies in our knowledge of vector biology and vectorial capacity also hinder public health efforts for vector control. Challenges to dengue and malaria control are discussed, and research priorities identified. PMID- 24215778 TI - Comparison of PCR and conventional blood culture to analyze blood from dogs with suspected sepsis. AB - Sepsis carries a poor prognosis in critically ill dogs. PCR-based diagnostics could be more sensitive for detecting bacteremia than conventional blood culture, allowing earlier initiation of appropriate therapy. Molecular techniques have been considered as ancillary tools for detecting bacteremia and identifying pathogens in humans and in dogs with bacterial endocarditis. This study compared PCR analysis and blood culture for detecting bacteremia in six dogs with suspected sepsis and six healthy control dogs. One blood culture from a dog with suspected sepsis was positive but none from the healthy controls. PCR was negative for extracts from all dogs. This pilot study does not support the hypothesis that culture-independent PCR-based techniques used directly on small samples of blood are useful for diagnosing bacteremia in dogs with suspected sepsis. PMID- 24215779 TI - A loud right-apical systolic murmur is associated with the diagnosis of secondary pulmonary arterial hypertension: retrospective analysis of data from 201 consecutive client-owned dogs (2006-2007). AB - Canine pulmonary arterial hypertension (PAH) remains under-recognized and under treated despite being prevalent. This retrospective study investigated whether selected historical and physical examination findings were associated with the diagnosis of canine PAH, defined as tricuspid regurgitation (TR) with a confirmed systolic pressure gradient >= 35 mm Hg. Two hundred and one client-owned dogs (PAH group, n=96; control group, n=105) were studied. Dogs in the control group had TR with a confirmed systolic gradient <35 mm Hg. All dogs underwent a complete physical examination and a complete echocardiographic assessment. A loud systolic right-apical murmur (RAM) was significantly associated with TR >= 35 mm Hg. The proportion of dogs with PAH significantly increased as the RAM grade increased, with odds ratios of 4.4-37.6 for Grades 3/6-5/6 (P=0.004 to <0.001), respectively. A stronger right-than-left apical-murmur had a positive predictive value (PPV) of 83% and was 96% specific for TR >= 35 mm Hg, and when combined with syncope, it had a PPV of 92% and was 92% specific. A Grade >= 4/6 RAM had a PPV of 85% and was 93% specific. Syncope with a Grade >= 4/6 RAM had a PPV of 94% and was 92% specific. Ascites combined with a Grade >= 4 or >= 5/6 RAM had a PPV of 100% and was 100% specific for TR >= 35 mm Hg. For each of these three murmur categories (Grades >= 4/6, >= 5/6, and a louder-right-than-left murmur), when detected with no concurrent ascites or syncope, the positive likelihood ratio varied from 4.6 to 6.4. A loud systolic RAM in dogs with degenerative valve disease is highly suggestive of concurrent PAH. PMID- 24215777 TI - Chemical genomics for studying parasite gene function and interaction. AB - With the development of new technologies in genome sequencing, gene expression profiling, genotyping, and high-throughput screening of chemical compound libraries, small molecules are playing increasingly important roles in studying gene expression regulation, gene-gene interaction, and gene function. Here we briefly review and discuss some recent advancements in drug target identification and phenotype characterization using combinations of high-throughput screening of small-molecule libraries and various genome-wide methods such as whole-genome sequencing, genome-wide association studies (GWAS), and genome-wide expression analysis. These approaches can be used to search for new drugs against parasite infections, to identify drug targets or drug resistance genes, and to infer gene function. PMID- 24215780 TI - Blood glucose, acid-base and electrolyte changes during loading doses of alpha2 adrenergic agonists followed by constant rate infusions in horses. AB - The aim of the present study was to investigate changes in blood glucose concentration ([Glu]B), acid-base status and electrolyte concentrations during constant rate infusions (CRI) of two alpha2-adrenergic agonists in seven horses treated in a blinded, randomised, crossover design with xylazine or romifidine. An intravenous (IV) bolus of xylazine (1mg/kg) or romifidine (80 MUg/kg) was administered followed by an IV CRI of xylazine (0.69 mg/kg/h) or romifidine (30 MUg/kg/h) for 2h. Blood samples were collected from the pulmonary artery before and after loading doses, during the CRI, and for 1h after discontinuing drugs. Blood glucose, base excess (BE), pH, partial pressure of carbon dioxide (Pv-CO2), strong ion difference (SIDest) and bicarbonate concentration ( [Formula: see text] ) increased significantly during the CRI with both alpha2-adrenergic agonists. Chloride concentration ([Cl(-)]B) and anion-gap (AG) decreased significantly compared to baseline. The decrease in sodium concentration ([Na(+)]B) was only significant with xylazine. From 1h after starting the CRI onwards, [Glu]B was significantly higher with romifidine compared to xylazine. Except [Glu]B, SIDest, and Pv-CO2, all variables returned to normal values 1h after discontinuing xylazine. After stopping romifidine, all variables except pH remained altered for at least 1h. It was concluded that loading doses of alpha2 adrenergic agonists followed by CRIs produce [Glu]B, acid-base and electrolyte changes. The clinical significance of the reported changes remains to be investigated and absolute values should be interpreted with caution, as fluid boli were used for cardiac output measurements, but may become important during prolonged infusion and in critically ill patients. PMID- 24215781 TI - Absence of KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles. AB - To date, two maternal-effect genes have been shown to play causal roles in recurrent hydatidiform moles (RHMs). NLRP7, a major gene for this condition, codes for a nucleotide-binding oligomerization domain-like receptor and is mutated in 48 to 60% of patients with RHMs. KHDC3L is a recently identified gene that is mutated in 14% of NLRP7-negative patients. We screened KHDC3L for mutations in a total of 101 Chinese patients, 15 with at least two hydatidiform moles, 16 with at least two reproductive losses including one hydatidiform mole, and 70 with one hydatidiform mole and no other form of reproductive loss, but did not find any mutation. Our data favor the causal role of KHDC3L in a minority of RHM cases, demonstrate its noninvolvement in other forms of reproductive loss, and indicate the presence of other unidentified genes that cause or increase patients' susceptibility to RHMs in the Chinese population. PMID- 24215782 TI - Review: putative roles for the macrophage migratory inhibitory factor at the maternal fetal interface. AB - Complex and dynamic networks of molecules participate in the essential interactions between maternal organism, placenta and fetus in a healthy and successful pregnancy. Macrophage migratory inhibitory factor (MIF) is one of several molecules produced at implantation sites; MIF is mostly expressed by trophoblast cells. This has led to expectations of MIF's relevance as a partner in the maternal/fetal dialog. MIF is known by its biological interactions and functional roles as an activator of innate immunity, regulating subsequent adaptive responses, which include inhibition of migration of mononuclear cells in vitro, antagonism of glucocorticoids, and regulation of expression of Toll-like receptor 4. Beyond roles in the inflammatory response, MIF can interfere with proliferative activities in different cell types, as well as with cell death pathways. This intriguing factor found at the human, porcine, ovine, bovine and rodent maternal-fetal interfaces is present in a time- and spatially-dependent manner, indicating regulatory roles in the process of embryo implantation, placental development, maintenance of pregnancy and birth. Here, we will review MIF participation in placental physiology, including new evidence for a dialog with uterine cells, and a potential role in protection of uterine decidual cells. PMID- 24215783 TI - Gellan gum nanohydrogel containing anti-inflammatory and anti-cancer drugs: a multi-drug delivery system for a combination therapy in cancer treatment. AB - During the last decades, it has become evident that inflammation plays a critical role in tumorigenesis: tumor microenvironment is largely orchestrated by inflammatory cells. In the present work, a novel gellan gum nanohydrogel system (NH) able to carry and deliver simultaneously anti-cancer and anti-inflammatory drugs was developed. Prednisolone was chemically linked to the carboxylic groups of gellan gum to serve as a hydrophobic moiety promoting nanohydrogel formation, whereas paclitaxel was then physically entrapped in it. NH improved drug performances, acting as paclitaxel and prednisolone solubility enhancer and favoring the drug uptake in the cells. Moreover, NH allowed an increased cytotoxic effect in vitro on several types of cancer cells due to the synergistic effect of the combination of anti-inflammatory and anti-cancer drugs. Thus, NH can be useful in a combination therapy that attacks both, malignant cells and tumor inflammatory components. PMID- 24215784 TI - Chronic kidney disease and hypothalamic-pituitary axis dysfunction: the chicken or the egg? AB - Hormonal derangements at the level of the hypothalamic-pituitary axis are often seen with the worsening of kidney function. This may not be surprising given the role of the kidney in synthesis, metabolism and elimination of many of these hormones. Traditionally, these derangements have been understood as a consequence of kidney failure. Conversely, recent evidence points towards the implication of such hormonal disorders in the genesis of CKD. In this review we present arguments supporting both the role of hypothalamic-pituitary axis dysfunction as a consequence of uremic complications and a culprit in disease incidence and progression. Focus is given to evidence regarding thyroidal, adrenal and gonadal axes. PMID- 24215785 TI - Multidisciplinary strategies in the management of early chronic kidney disease. AB - Chronic kidney disease (CKD) is a worldwide epidemic especially in developing countries, with clear deficiencies in identification and treatment. Better care of CKD requires more than only economic resources, utilization of health research in policy-making and health systems changes that produce better outcomes. A multidisciplinary approach may facilitate and improve management of patients from early CKD in the primary health-care setting. This approach is a strategy for improving comprehensive care, initiating and maintaining healthy behaviors, promoting teamwork, eliminating barriers to achieve goals and improving the processes of care. A multidisciplinary intervention may include educational processes guided by health professional, use of self-help groups and the development of a CKD management plan. The complex and fragmented care management of patients with CKD, associated with poor outcome, enhances the importance of implementing a multidisciplinary approach in the management of this disease from the early stages. Multidisciplinary strategies should focus on the needs of patients (to increase their empowerment) and should be adapted to the resources and health systems prevailing in each country; its systematic implementation can help to improve patient care and slow the progression of CKD. PMID- 24215786 TI - Peritoneal fluid transport: mechanisms, pathways, methods of assessment. AB - Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. PMID- 24215788 TI - Retirement of Wolfgang Sachse as Editor-in-Chief of Ultrasonics. PMID- 24215789 TI - Challenges in the diagnosis of ethylene glycol poisoning. AB - Ethylene glycol poisoning, while uncommon, is clinically significant due to the associated risk of severe morbidity or lethality and it continues to occur in many countries around the world. The clinical presentation of ethylene glycol toxicity, while classically described in three phases, varies widely and when combined with the range of differential diagnoses that must be considered makes diagnosis challenging. Early and accurate detection is important in these patients, however, as there is a need to start antidotal treatment early to prevent serious harm. In this article, we will review the literature and provide guidance regarding the diagnosis of ethylene glycol poisoning. While gas chromatography is the gold standard, the usefulness of this test is hampered by delays in access due to availability. Consequently, there are several surrogate markers that can give an indication of ethylene glycol exposure but these must be interpreted with caution and within the clinical context. An in-depth review of these tests, particularly the detection of a raised osmolar gap or an raised anion gap acidosis, will form the main focus of this article. PMID- 24215787 TI - A patient with medication-resistant epilepsy featuring psychosensorial and psychotic symptoms presenting with significant functional improvement on psychotherapeutic treatment: a case report. AB - BACKGROUND: Partial complex epilepsy with psychosensorial and psychotic symptoms remains a relatively rare condition that can sometimes be mistaken for an axis I psychiatric disorder. There is no specific treatment for this particular type of epilepsy, anti-epileptic medication being the cornerstone of therapeutic intervention with the occasional addition of neuroleptics. Lack of response to anti-epileptic agents is often a sign of poor prognosis and requires risky and sometimes invasive interventions with high morbidity for patients. CASE PRESENTATION: We report the case of a 21-year-old right-handed Caucasian man of French-Canadian descent who was living with his mother immediately before being hospitalized in a psychiatric setting for the first time. He seemed obsessed with developing new concepts to reach a more 'perfect' existence. He also claimed feeling odd sensations in his mind and in his body that could be linked to some sort of 'evolutionary' process resulting from spiritual uplift. He reported non specific visual hallucinations and what sounded like auditory hallucinations and telepathic powers. The first diagnosis was a possible schizophreniform disorder and our patient was hospitalized. Shortly afterwards, an electroencephalogram showed an important subcortical epileptic activity, compatible with partial complex epilepsy with psychosensorial and psychotic symptoms. Despite a negative response to medication, symptoms proper to this type of epilepsy were substantially alleviated using a psychotherapeutical treatment intended for patients with psychotic disorders, namely integrated psychological therapy (IPT). Significant functional improvement in our patient has been achieved since then. CONCLUSIONS: This case report illustrates that despite a negative response to medication, symptoms proper to this type of epilepsy could be substantially alleviated using psychotherapeutical treatment modalities. To the best of our knowledge, this is the first time such a finding has been reported in the scientific literature. This could open the way for new research themes and therapeutic interventions for such patients. PMID- 24215790 TI - Sunitinib effects on the radiation response of endothelial and breast tumor cells. AB - BACKGROUND: Endothelial cells are suggested regulators of tumor response to radiation. Anti-vascular targeting agents can enhance tumor response by targeting endothelial cells. Here, we have conducted experiments in vitro to discern the effects of radiation combined with the anti-angiogenic Sunitinib on endothelial (HUVEC) and tumor (MDA-MB-231) cells, and further compared findings to results obtained in vivo. METHODS: In vitro and in vivo treatments consisted of single dose radiation therapy of 2, 4, 8 or 16 Gy administered alone or in combination with bFGF or Sunitinib. In vitro, in situ end labeling (ISEL) was used to assess 24-hour apoptotic cell death, and clonogenic assays were used to assess long-term response. In vivo MDA-MB-231 tumors were grown in CB-17 SCID mice. The vascular marker CD31 was used to assess 24-hour acute response while tumor clonogenic assays were used to assess long-term tumor cell viability following treatments. RESULTS: Using in vitro studies, we observed an enhanced endothelial cell response to radiation doses of 8 and 16 Gy when compared to tumor cells. Administering Sunitinib alone significantly increased HUVEC cell death, while having modest additive effects when combined with radiation. Sunitinib also increased tumor cell death when combined with 8 and 16 Gy radiation doses. In comparison, we found that the clonogenic response of in vivo treated tumor cells more closely resembled that of in vitro treated endothelial cells than in vitro treated tumor cells. CONCLUSION: Our results indicate that the endothelium is an important regulator of tumor response to radiotherapy, and that Sunitinib can enhance tumor radiosensitivity. To the best of our knowledge, this is the first time that Sunitinib is investigated in combination with radiotherapy on the MDA MB-231 breast cancer cell line. PMID- 24215791 TI - Sexual interest in children among an online sample of men and women: prevalence and correlates. AB - The purpose of the present study was to explore the extent to which men and women in the general population report sexual interest in children and to examine distinct developmental experiences associated with self-reported sexual interest. Participants (262 females and 173 males) were recruited online and completed a questionnaire assessing sexual interest and adverse childhood experiences. Among men, 6% indicated some likelihood of having sex with a child if they were guaranteed they would not be caught or punished, as did 2% of women. Nine percent of males and 3% of females indicated some likelihood of viewing child pornography on the Internet. Overall, nearly 10% of males and 4% of females reported some likelihood of having sex with children or viewing child pornography. Males and females with any sexual interest in children reported higher likelihoods of engaging in other antisocial or criminal behaviors and also reported more dysfunctional childhoods (i.e., histories of sexual abuse, insecure parent-child attachments). Theoretical implications of the findings and suggestions for preventing the sexual victimization of children are provided. PMID- 24215792 TI - Mitochondrial DNA variations associated with hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is a primary disorder, characterized by unexplained hypertrophy of the left ventricle that frequently involved in the inter-ventricular septum. Mitochondrial DNA (mtDNA) mutations and haplogroups have been found to be associated with several diseases. Therefore, in the present study, we have sequenced the complete mtDNA of 114 clinically well-characterized HCM patients to look for the role of mtDNA variations and haplogroups in HCM phenotype among Indian patients. Complete mtDNA analysis revealed 28 novel variations, 25 disease-associated and 50 private mutations. We found 13 (11.40%) HCM patients having novel non-synonymous and/or MT-tRNA variations, of which two (m.4797C>M and m.8728T>Y) were in heteroplasmic condition. In silico prediction showed that a few mutations are pathogenic, which may affect the energy production in the heart. Unlike some of the other studies, we did not find association of mitochondrial haplogroup with HCM. PMID- 24215794 TI - How much evidence is required for a paradigm shift in mental health? PMID- 24215793 TI - Insulin resistance alters islet morphology in nondiabetic humans. AB - Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic beta cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of beta- and alpha-cells that resulted in an altered beta-cell-to-alpha-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of alpha-cells are potential contributors to the beta-cell compensatory response to insulin resistance in the absence of overt diabetes. PMID- 24215796 TI - The role of allopregnanolone in depression and anxiety. AB - Neuroactive steroids such as allopregnanolone do not only act as transcriptional factors in the regulation of gene expression after intracellular back-oxidation into the 5-alpha pregnane steroids but may also alter neuronal excitability through interactions with specific neurotransmitter receptors. In particular, certain 3alpha-reduced metabolites of progesterone such as 3alpha,5alpha tetrahydroprogesterone (allopregnanolone) and 3alpha,5beta-tetrahydroprogesterone (pregnanolone) are potent positive allosteric modulators of the GABA(A) receptor complex. During the last years, the downregulation of neurosteroid biosynthesis has been intensively discussed to be a possible contributor to the development of anxiety and depressive disorder. Reduced levels of allopregnanolone in the peripheral blood or cerebrospinal fluid were found to be associated with major depression, anxiety disorders, premenstrual dysphoric disorder, negative symptoms in schizophrenia, or impulsive aggression. The importance of allopregnanolone for the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but probably also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function. Certain pharmacokinetic obstacles limit the therapeutic use of natural neurosteroids (low bioavailability, oxidation to the ketone). Until now synthetic neuroactive steroids could not be established in the treatment of anxiety disorders or depression. However, the translocator protein (18 kDa) (TSPO) which is important for neurosteroidogenesis has been identified as a potential novel target. TSPO ligands such as XBD 173 increase neurosteroidogenesis and have anxiolytic effects with a favorable side effect profile. PMID- 24215797 TI - The international view of envenoming in Brazil: myths and realities. AB - Being distant from Brazil's great natural diversity, from its long tradition in the study of snakebites and from the fact that it is one of the few countries which has a national information system for monitoring incidents involving venomous animals, non-Brazilian researchers face risks when estimating the incidence of these accidents in the country. The present work offers a critical review of the main estimates undertaken since 1954. It is interesting to note contradictions between textual and graphic information within the same article, variations over time in the work of a same researcher and differences among distinct authors, and that all these issues remain unmentioned or undiscussed. Comparison among such estimates and the data available at the Brazilian Information System on Diseases of Compulsory Declaration (Sistema de Informacao de Agravos de Notificacao - SINAN) creates an opportunity to identify the degree of imprecision present in those articles, and draws attention to the need for the production of studies at both the regional and national levels, based on concrete data collected at national, state and municipal levels, which has been available on the internet since 2001. PMID- 24215798 TI - Epidemiology and genetic diversity of multidrug-resistant tuberculosis in East Africa. AB - Multidrug-resistant tuberculosis (MDR-TB) is an emerging problem in many parts of the world, and levels of MDR-TB among new TB patients are increasing in sub Saharan Africa. We reviewed the prevalence and molecular epidemiology of MDR-TB in East Africa, including Burundi, Kenya, Rwanda, Tanzania, and Uganda. In 16 epidemiologic surveys, the prevalence of MDR among new cases ranges from 0.4% in Tanzania to 4.4% in Uganda, and among recurrent cases ranges from 3.9% in Tanzania to 17.7% in Uganda. There is a gap of 5948 cases between the estimated number of MDR-TB cases in East Africa and the number actually diagnosed. The only confirmed risk factors for MDR-TB are prior treatment for TB and refugee status. HIV has not been reported as a risk factor, and there are no reports of statistical association between spoligotype and drug resistance pattern. Increased capacity for diagnosis and treatment of MDR-TB is needed, with an emphasis on recurrent TB cases and refugees. PMID- 24215799 TI - Orexin in sleep, addiction and more: is the perfect insomnia drug at hand? AB - Orexins A and B (hypocretins 1 and 2) and their two receptors (OX1R and OX2R) were discovered in 1998 by two different groups. Orexin A and B are derived from the differential processing of a common precursor, the prepro-orexin peptide. The neuropeptides are expressed in a few thousand cells located in the lateral hypothalamus (LH), but their projections and receptor distribution are widespread throughout the brain. Remarkably, prepro peptide and double (OX1R/OX2R) receptor knock out (KO) mice reproduce a sleep phenotype known in humans and dogs as narcolepsy/cataplexy. In humans, this disease is characterized by the absence of orexin producing cells in the LH, and severely depleted levels of orexin the cerebrospinal fluid. Null mutation of the individual OX1R or OX2R in mice substantially ameliorates the narcolepsy/cataplexy phenotype compared to the OX1R/OX2R KO, and highlights specific roles of the individual receptors in sleep architecture, the OX1R KO demonstrating an a attenuated sleep phenotype relative to the OX2R KO. It has therefore been suggested that orexin is a master regulator of the sleep-wake cycle, with high activity of the LH orexin cells during wake and almost none during sleep. Less than 10years later, the first orexin antagonist, almorexant, a dual orexin receptor antagonist (DORA), was reported to be effective in inducing sleep in volunteers and insomnia patients. Although development was stopped for almorexant and for Glaxo's DORA SB-649868, no less than 4 orexin receptor antagonists have reached phase II for insomnia, including Filorexant (MK-6096) and Suvorexant (MK-4305) from Merck. Suvorexant has since progressed to Phase III and dossier submission to the FDA. These four compounds are reported as DORAs, however, they equilibrate very slowly at one and/or the other orexin receptor, and thus at equilibrium may show more or less selectivity for OX1R or OX2R. The appropriate balance of antagonism of the two receptors for sleep is a point of debate, although in rodent models OX2R antagonism alone appears sufficient to induce sleep, whereas OX1R antagonism is largely devoid of this effect. Orexin is involved in a number of other functions including reward and feeding, where OX1R (possibly OX2R) antagonists display anti-addictive properties in rodent models of alcohol, smoking, and drug self-administration. However, despite early findings in feeding and appetite control, orexin receptor antagonists have not produced the anticipated effects in models of increased food intake or obesity in rodents, nor have they shown marked effects on weight in the existing clinical trials. The role of orexin in a number of other domains such as pain, mood, anxiety, migraine and neurodegenerative diseases is an active area of research. The progress of the orexin field is thus extraordinary, and the community awaits the clinical testing of more receptor selective antagonists in sleep and other disorders, as well as that of orexin agonists, with the latter expected to produce positive outcomes in narcolepsy/cataplexy and other conditions. PMID- 24215800 TI - Neuropeptides and hippocampal neurogenesis. AB - Hippocampal neurogenesis is important for modulating the behavioural responses to stress and for certain forms of learning and memory. The mechanisms underlying the necessary coupling of neuronal activity to neural stem/progenitor cell (NSPC) function remain poorly understood. Within the dentate subgranular stem cell niche, local interneurons appear to play an important part in this excitation neurogenesis coupling via GABAergic transmission, which promotes neuronal differentiation and integration. Neuropeptides such as neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and galanin have emerged as important mediators for signalling local and extrinsic interneuronal activity to subgranular zone precursors. Here we review the distribution of these neuropeptides and their receptors in the neurogenic area of the hippocampus and their precise effects on hippocampal neurogenesis. We also discuss neuropeptides' potential involvement in functional aspects of hippocampal neurogenesis particularly their involvement in the modulation of learning and memory and behavior responses. PMID- 24215801 TI - Increasing the number of chews before swallowing reduces meal size in normal weight, overweight, and obese adults. AB - Eating slowly contributes to a lower risk of obesity, probably because it could aid appetite control. Chewing thoroughly is an effective strategy to reduce eating rate; however, insufficient data are available to demonstrate the relationship between such an eating behavior and energy intake. To investigate the effect of increasing the number of chews before swallowing on meal size, a randomized cross-over trial was conducted in 18- to 45-year-old normal-weight, overweight, and obese participants (n=45) who were recruited from the local community (Ames, IA). After assessment of baseline number of chews, participants were asked to attend three test sessions to eat pizza for lunch until comfortably full by chewing each portion of food either 100%, 150%, or 200% of their baseline number of chews before swallowing. Two-way analysis of variance was used to test the effect of treatment and body-weight status, as well as their interactions on food intake, meal duration, eating rate, and appetite at meal termination. Appetite data during 60 minutes were analyzed by repeated measures analysis of variance. Food intake in the sessions with 150% and 200% of their baseline number of chews was reduced significantly, by 9.5% and 14.8%, respectively, compared with the 100% session. Increasing the number of chews also prolonged meal duration and reduced eating rate. However, subjective appetite at meal termination or during the immediate postprandial period did not differ. These data indicate that increasing the number of chews before swallowing might be a behavioral strategy to reduce food intake and potentially aid body-weight management. PMID- 24215802 TI - Pupil size and anisocoria in children measured by the plusoptiX photoscreener. AB - PURPOSE: To investigate pupil size and the incidence of anisocoria in children at a single community-based practice using the plusoptiX A04 and A09 photoscreeners (plusoptiX GmbH, Nuremberg, Germany). METHODS: The medical records of consecutive patients <1 to 17 years of age who had received a comprehensive ophthalmological examination that included photoscreening with the plusoptiX were retrospectively reviewed. Data collected included sizes of both pupils, age, sex, laterality, and magnitude of anisocoria. RESULTS: A total of 1,306 patient records were reviewed. Of these, 1,057 (80.9%) had 0-0.4 mm of anisocoria; 219 (16.8%), 0.5-0.9 mm; 20 (1.5%), 1.0-1.4 mm; and 10 (0.8%), >=1.5 mm. Magnitude of anisocoria appears to increase with age (P = 0.0073). Pupil size and age were positively correlated (P < 0.0001), that is, older children had larger pupils. Average pupil size of children <1 year of age was 5.0 mm; of children >=16 years of age, 6.1 mm. When sorted into age buckets of 0-3, 4-7, 8-11, 12-15, and 16-17, this increase becomes apparent. There is no significant relationship between pupil size and sex (P = 0.14). CONCLUSIONS: Our study of 1,306 children shows that pupil size increases through childhood, and that 19.1% of children in a clinical population have anisocoria >0.4 mm. PMID- 24215803 TI - Preoperative cataract surgery use of an intravitreal dexamethasone implant (Ozurdex) in a patient with juvenile idiopathic arthritis and chronic anterior uveitis. AB - We report a 6-year-old boy with anterior uveitis associated with juvenile idiopathic arthritis (JIA) who underwent cataract extraction in his right eye. One month before surgery he received an intravitreal sustained-release dexamethasone implant. During 10 months' follow-up, his uveitis remained quiet. To our knowledge this is the first report using an intravitreal sustained-release dexamethasone implant as a perioperative anti-inflammatory medication. PMID- 24215804 TI - Reply: To PMID 23791404. PMID- 24215805 TI - Management of large V-pattern exotropia with minimal or no inferior oblique overaction. AB - PURPOSE: To compare the outcomes of patients with large V-pattern exotropia and minimal inferior overaction who underwent bilateral lateral rectus recession combined with full-tendon-width upward transposition of the lateral rectus muscles or bilateral inferior oblique myectomy. METHODS: The medical records of consecutive patients with V-pattern exotropia (at least 20(Delta) greater in upgaze than in downgaze) with minimal inferior oblique overaction who underwent either of the above procedures and who had at least 6 months' follow-up were retrospectively reviewed. Pre- and postoperative ductions, versions, pattern strabismus, stereoacuity and fundus torsion were analyzed. Success was defined as esophoria <8(Delta)/tropia <=5(Delta) to exophoria/tropia <=8(Delta) in primary gaze. RESULTS: A successful outcome was achieved in 9 patients (56%) in the transposition group and 13 (72%) in the myectomy group (P = 0.48). Reduction of V pattern to <10(Delta) was achieved in 7 cases (44%) in the transposition group and 14 (78%) in the myectomy group (P = 0.04), with mean reductions of 16(Delta) +/- 5(Delta) and 25(Delta) +/- 5(Delta), respectively (P = 0.03). In the myectomy group, 4 patients (22%) had overcorrection with consecutive A patterns of 2(Delta)-6(Delta). CONCLUSIONS: In patients with a V pattern exotropia and minimal inferior oblique over action, bilateral lateral rectus recessions plus bilateral inferior oblique myectomy can successfully eliminate the V pattern but the surgery may occasionally result in overcorrection with consecutive A pattern. PMID- 24215806 TI - Pediatric traumatic hyphema: a review of 138 consecutive cases. AB - PURPOSE: To report the demographics and outcomes in children (<18 years of age) who developed hyphema from ocular trauma and were subsequently cared for at a tertiary medical center. METHODS: The medical records of consecutive patients seen at Children's Hospital Colorado diagnosed with traumatic hyphema between September 1, 2003, and December 31, 2011, were retrospectively reviewed. The following data were recorded: patient age, parent/guardian-reported ethnicity, sex, injury location, visual acuity, and intraocular pressure (IOP) at presentation and follow-up. RESULTS: A total of 138 cases of unilateral hyphema were included, with 88% occurring in boys (mean age, 10.1 years; range, 1-19). Over 90% of injuries occurred in the home setting, with the most common mechanisms of injury being general play, projectiles from guns, and sports injuries occurring during games or practice. Only 3 patients had visual acuity <20/40 at 1 month's follow-up, and no patient experienced a rebleeding event. Most of the 33 patients with elevated IOP were managed medically; 4 (12%) required surgery. CONCLUSIONS: The majority of children with traumatic hyphema in this patient cohort were injured in the home setting. Very few patients underwent surgery for ocular hypertension, but higher IOP at presentation was associated with the need for surgical intervention. Outpatient care with activity restriction and topical medications usually led to resolution of hyphema without serious complications or visual loss. PMID- 24215807 TI - Retinal hemorrhage and brain injury patterns on diffusion-weighted magnetic resonance imaging in children with head trauma. AB - PURPOSE: To evaluate associations between retinal hemorrhage severity and hypoxic ischemic brain injury (HII) patterns by diffusion-weighted magnetic resonance imaging (DW-MRI) in young children with head trauma. METHODS: DW-MRI images of a consecutive cohort study of children under age 3 years with inflicted or accidental head trauma who had eye examinations were analyzed by two independent masked examiners for type, severity, and location of primary lesions attributable to trauma, HII secondary to trauma, and mixed injury patterns. Retinal hemorrhage was graded retrospectively on a scale from 1 (none) to 5 (severe). RESULTS: Retinal hemorrhage score was 3-5 in 6 of 7 patients with predominantly post traumatic HII pattern and 4 of 32 who had traumatic injury without HII (P < 0.001) on DW-MRI imaging. Severe retinal hemorrhage was observed in absence of HII but only in inflicted injury. Retinal hemorrhage severity was correlated with HII severity (rho = 0.53, P < 0.001) but not traumatic injury severity (rho = 0.10, P = 0.50). HII severity was associated with retinal hemorrhage score 3-5 (P = 0.01), but traumatic injury severity was not (P = 0.37). CONCLUSIONS: During inflicted head injury, a distinct type of trauma occurs causing more global brain injury with HII and more severe retinal hemorrhages. HII is not a necessary factor for severe retinal hemorrhage to develop from inflicted trauma. PMID- 24215808 TI - Risk factors influencing the outcome of strabismus surgery following retinal detachment surgery with scleral buckle. AB - PURPOSE: To determine factors associated with surgical success in patients undergoing strabismus surgery after retinal detachment repair with scleral buckle. METHODS: The medical records of consecutive patients who underwent strabismus surgery after repair of retinal detachment with scleral buckle were retrospectively reviewed. A successful "motor" outcome was defined as horizontal deviation <10(Delta) and vertical deviation <4(Delta) in the primary position; successful "sensory" outcome was no diplopia in the primary position. Various factors such as removing the scleral buckle at the time of strabismus surgery, the macula structural status, size of the preoperative deviation, presence of restriction to passive movement, and whether the eye with the scleral buckle was the operated eye were compared among groups based on motor success. RESULTS: A total of 25 patients were included. The overall motor success rate was 72% after 1.8 +/- 0.9 operations, with 62% of patients diplopia free in the primary position. Horizontal deviation <10(Delta) (P = 0.005) and minimal restriction on forced duction test were associated with motor success after the first surgery (P = 0.05). Partial or entire scleral buckle removal (n = 15) and fellow-eye surgery were not significantly correlated with motor success in our cohort. There were no retinal redetachments after scleral buckle removal. CONCLUSIONS: A small preoperative horizontal deviation, and minimally restricted ocular rotations were associated with better results. Removing the scleral buckle did not improve results. PMID- 24215810 TI - Modulating caspase activity: beyond the active site. AB - Caspases are a family of aspartate-specific cysteine proteases that regulate cellular homeostasis through the mediation of apoptosis and inflammation. Despite keen interest in caspases as therapeutic targets for cancer, inflammatory, and neurodegenerative diseases, no active-site directed small molecule has yet succeeded in navigating human clinical trials. At the same time, recent biochemical and biophysical studies have revealed caspases to be highly dynamic proteases possessing a remarkable diversity of activation mechanisms. In addition, many caspases possess an allosteric circuit linking key active site loops with a distal allosteric site located at the dimer interface. Accordingly, small molecule binding at this allosteric site directly impacts structural organization of the active site and thus catalytic activity. Both cysteine tethered and non-covalent reversible small molecules have recently been identified for these allosteric sites, with binding producing a variety of functional effects. Surprising new examples of caspase modulation have also been described recently, including a small molecule that binds caspase-6-substrate complexes uncompetitively and a short peptide that stabilizes an inactive, tetrameric form of procaspase-6. The confluence of recent biochemical, biophysical and pharmacological data has revealed exciting new avenues for the modulation of caspase activity via binding beyond the active site. PMID- 24215809 TI - The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study. AB - BACKGROUND: An elevated PI/I ratio is attributable to increased secretory demand on beta-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT). METHODS: MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride. RESULTS: Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders. CONCLUSIONS: Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired beta-cell function from the viewpoint of the PI/I ratio. TRIAL REGISTRATION UMIN-CTR: UMIN000010467. PMID- 24215812 TI - The VANILLA sensor as a beam monitoring device for X-ray radiation therapy. AB - Cancer treatments such as intensity-modulated radiotherapy (IMRT) require increasingly complex methods to verify the accuracy and precision of the treatment delivery. In vivo dosimetry based on measurements made in an electronic portal imaging device (EPID) has been demonstrated. The distorting effect of the patient anatomy on the beam intensity means it is difficult to separate changes in patient anatomy from changes in the beam intensity profile. Alternatively, upstream detectors scatter and attenuate the beam, changing the energy spectrum of the beam, and generate contaminant radiation such as electrons. We used the VANILLA device, a Monolithic Active Pixel Sensor (MAPS), to measure the 2D beam profile of a 6 MV X-ray beam at Bristol Hospital in real-time in an upstream position to the patient without clinically significant disturbance of the beam (0.1% attenuation). MAPSs can be made very thin (~20 MUm) with still a very good signal-to-noise performance. The VANILLA can reconstruct the collimated beam edge with approximately 64 MUm precision. PMID- 24215811 TI - Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2 methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. AB - We present a traumatic fatality of a 19-year-old man who had ingested blotter paper containing 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2 methoxyphenyl)methyl]ethanamine]. Postmortem specimens were analyzed by high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Toxicology findings for fluids based upon blood or urine calibrators were as follows: peripheral blood, 405 pg/mL; heart blood, 410 pg/mL; urine, 2.86 ng/mL; and vitreous humor, 99 pg/mL. While findings based upon the method of standard additions were: gastric contents, 7.1 MUg total; bile, 10.9 ng/g; brain, 2.54 ng/g and liver, 7.2 ng/g. To our knowledge the presented case is the first postmortem case of 25I-NBOMe intoxication documented by toxicological analysis of tissues and body fluids. PMID- 24215813 TI - Investigation of the relationships between seismic activities and radon level in western Turkey. AB - The distribution of radon activity is determined from pre-earthquake data. Analysis using Normal, Gamma, Weibull and Rayleigh distributions indicates that the variation of radon levels in seismically active regions is best described by a normal distribution. It was observed that radon levels would change in compressive fault lines prior to earthquake. Besides that it tended to increase before the earthquake and then decrease towards the time of earthquake occurrences. PMID- 24215814 TI - Activation cross-sections of long lived products of deuteron induced nuclear reactions on dysprosium up to 50 MeV. AB - Activation cross-sections for production of (162m,161,155)Ho, (165,159,157,155)Dy and (161,160,156,155)Tb radionuclides in deuteron induced nuclear reactions on elemental dysprosium were measured up to 50 MeV for practical application and the test of the predictive power of nuclear reaction model codes. A stacked-foil irradiation technique and off-line gamma-ray spectrometry were used to determine the activities. No earlier cross-section data were found in the literature. The experimental data are compared with the predictions of the ALICE-D, EMPIRE-D and TALYS codes. Integral production yields were calculated from the fitted experimental data. PMID- 24215815 TI - Activation cross-sections of deuteron induced reactions on (nat)Gd up to 50 MeV. AB - Activation cross-sections are presented for the first time for (nat)Gd(d,xn)(161,160,156(m+)), (154,154m1,154m2,153,152(m+),151(m+))Tb, (nat)Gd(d,x)(159,153,151)Gd and (nat)Gd(d,x)(156)Eu reactions from their respective thresholds up to 50 MeV. The cross-sections were measured by the stacked-foil irradiation technique and by using high resolution gamma-ray spectrometry. The measured values were compared with the results of theoretical models calculated by the computer codes ALICE-D, EMPIRE-D and TALYS (data from TENDL library). Integral yields of the reaction products were deduced from the excitation functions. PMID- 24215816 TI - A survey of medical students on their attitudes towards face transplantation. AB - The aim of this study was to assess and analyse the attitudes of medical students towards face transplantation. Medical students at the University of Cape Town were prospectively surveyed using a self-administered questionnaire. There were 402 participants; the mean age was 21 years (range 16-37 years), 35% were male and 65% were female. Only 12% were registered organ donors and 33% were interested in a surgical career. Two thirds of the respondents were in favour of face transplantation. Registered organ donors were the most willing to donate their face in the event of brain death (P = 0.00). Seventy-four percent of the respondents stated 'identity issues' as their main concern and 33% mentioned cost as a critical factor when considering the procedure. Personal experience with facial disfigurement and involvement in the care of a patient with facial disfigurement did not affect the willingness to donate or accept a face transplant, or the amount of support for the procedure (P > 0.05). This is the first study that exclusively describes the attitudes of medical students towards face transplantation. PMID- 24215817 TI - Identification of the relationships between sagittal plane and coronal plane curvature in guppy models. AB - OBJECTIVE: To explore the relationship between sagittal plane and coronal plane curvatures in guppies by investigating the curvature angles of sagittal and sagittal-coronal guppies. METHODS: After mating between 1000 spinal curvature guppies, 124 guppies (3-month old) were screened from progenies for the present study. Photos of all fishes were taken and the sagittal and coronal angles were calculated via angle measure tool of Photoshop 12.0 software. All data were analyzed by SPSS 11.0. RESULTS: In sagittal and sagittal-coronal curvature guppies, there was a significant linear correlation between sagittal angles and coronal angles. In 48 sagittal-coronal curvatures, their sagittal angles were above 40 degrees , meanwhile, in 76 sagittal guppies, their sagittal angles were mostly below 40 degrees . CONCLUSIONS: These findings indicated that the occurrence of coronal curvature might be later than sagittal curvature and could be influenced by other factors. Sagittal angles 40 degrees might be involved in the onset of coronal curvature. PMID- 24215818 TI - Overman rearrangement and Pomeranz-Fritsch reaction for the synthesis of benzoazepinoisoquinolones to discover novel antitumor agents. AB - The B-ring of Benzoazepinoisoquinolones 1a-b was successfully constructed by Pomeranz-Fritsch reaction. The key intermediates 5a-b could be transformed from 9a-b via Overman rearrangement. The bioassay showed that 11 compounds are more active than sorafenib (IC50 = 7.56 MUM) against A375 melanoma cell line, among which 1a, 5a, 8a and 10c with IC50 values of 0.59, 0.20, 0.17 and 0.11 MUM, respectively, showed potent cytotoxicity close to or even stronger than the anti melanoma drug vemurafenib (IC50 = 0.18 MUM). In addition, 5a, 8a and 10c are more active than both vemurafenib and sorafenib on HCT116 colon cell line (IC50 values: 0.86, 0.65, 0.42, >30 and 5.65 MUM for 5a, 8a, 10c, vemurafenib and sorafenib). Therefore, these compounds are promising candidates for further drug development. PMID- 24215819 TI - Identification of sulfonic acids as efficient ecto-5'-nucleotidase inhibitors. AB - Ecto-5'-nucleotidase (CD73) is well known for its implication in cancer. Inhibition of ecto-5'-nucleotidases is thought to provide an attractive approach to cancer therapy. This study identifies sulfonic acid compounds as efficient inhibitors of ecto-5'-nucleotidases. The compounds were tested against recombinant human and rat ecto-5'-nucleotidases. The most potent new sulfonic acid inhibitor 6-amino-4-hydroxynaphthalene-2-sulfonic acid (1) of ecto-5' nucleotidase had an IC50 of 1.32 +/- 0.09 MUM for the human and 10.4 +/- 3.3 MUM for the rat enzyme. Generally, all compounds were more active against the human enzyme. Plausible binding mode models were developed for this new class of inhibitors. Furthermore, several sulfonic acid inhibitors were efficient cytotoxic agents when tested on H157 cancer cell lines. Hence, new ecto-5' nucleotidases inhibitors displayed significant potential for further development as compounds for anti-cancer therapy. PMID- 24215820 TI - Bimanual coordination with three hands: is the mirror hand of any help? AB - The mirror paradigm has been used extensively both as a research tool for studying kinesthesia in healthy individuals and as a therapeutic tool for improving recovery and/or alleviating symptoms in patients. The present study of healthy participants assessed the contribution of the mirror paradigm to motor control in a bimanual coordination task performed under sensorimotor disturbance conditions. In Experiment 1, the participants were required to produce symmetrical circles with both hands/arms at the same time. In Experiment 2, the task consisted of synchronous extension-flexion movements of both arms in the sagittal plane. These tasks were performed under four different visual conditions: (i) mirror vision (i.e. with the non-dominant arm reflected in a mirror--the third hand--and the dominant arm hidden), (ii) full vision (i.e. both arms visible), (iii) with only the non-dominant arm visible and (iv) with the eyes closed. In Experiments 1 and 2, sensorimotor disturbance was applied to the participant's dominant arm by co-vibrating antagonistic muscles (the biceps and the triceps). In the complex circle drawing task, bimanual performance was better in the mirror condition than when participants saw their non-dominant arm only. However, motor performance in the mirror vision condition was little better than in the eyes closed condition, regardless of whether or not sensorimotor disturbance was applied. In Experiment 2, there were no differences between the "eyes closed" and "mirror vision" conditions. Although mirror reflection of one arm has been shown to induce consistent, vivid, perceptual illusions (kinesthetic illusion), our results suggest that it is less effective in modulating motor behavior. PMID- 24215821 TI - Anaerostipes rhamnosivorans sp. nov., a human intestinal, butyrate-forming bacterium. AB - A novel butyrate-producing bacterium, strain 1y-2(T), was isolated from a stool sample of a 1-year-old, healthy Dutch infant. The isolate was obtained by using lactate and acetate as sources of carbon and energy. The strain was Gram variable, strictly anaerobic and spore-forming and formed curly rod-shaped cells that fermented glucose into butyrate, lactate, formate and acetate as main products. The DNA G+C content of the strain was 44.5 mol% and its major cellular fatty acids were C12:0, iso-C19:1 I and C16:0. Strain 1y-2(T) was related to Anaerostipes caccae DSM 14662(T) based on 16S rRNA gene sequence analysis, with 3% divergence, but hybridization studies of their genomic DNA revealed only 33% relatedness. Moreover, strain 1y-2(T) showed marked physiological and biochemical differences from known species of the genus Anaerostipes. Based on phylogenetic, chemotypic and phenotypic criteria, we propose that strain 1y-2(T) should be classified in the genus Anaerostipes within a novel species, Anaerostipes rhamnosivorans sp. nov. The type strain is 1y-2(T) ( = DSM 26241(T) = KCTC 15316(T)). PMID- 24215822 TI - Meiothermus terrae sp. nov., isolated from a geothermally heated soil sample. AB - A Gram-negative, aerobic bacterium, designated strain YIM 77755(T), was isolated from a geothermally heated soil sample collected at Rehai National Park, Tengchong, Yunnan province, south-west China. Cells of the strain were rod-shaped and colonies were yellow and circular. Growth occurred in 0-1 % (w/v) NaCl, at pH 6.0-8.0 (optimum, pH 7.0) and at 35-55 degrees C (optimum, 50 degrees C). The predominant menaquinone was MK-8 and the DNA G+C content was 68.9 mol%. Major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0. The polar lipids consisted of an uncharacterized phospholipid and four glycolipids. Based on 16S rRNA gene sequence analysis, strain YIM 77755(T) formed a cluster with Meiothermus chliarophilus ALT-8(T) and showed the highest 16S rRNA gene sequence similarity to M. chliarophilus ALT-8(T) (98.23 %). DNA-DNA relatedness between YIM 77755(T) and M. chliarophilus DSM 9957(T) was 54.9+/-4.1 %. On the basis of the morphological and chemotaxonomic characteristics as well as genotypic data, it is proposed that strain YIM 77755(T) represents a novel species of the genus Meiothermus, named Meiothermus terrae sp. nov. The type strain is YIM 77755(T) ( = DSM 26712(T) = CCTCC AB 2012942(T)). PMID- 24215823 TI - Pseudoxanthomonas wuyuanensis sp. nov., isolated from saline-alkali soil. AB - A bacterium, designated XC21-2(T), was isolated from a saline-alkaline soil sample from China. Cells were Gram-stain-negative, rod-shaped and motile and grew optimally at 35-37 degrees C, pH 6.0-7.0 and in the presence of 0.5% (w/v) NaCl. Growth occurred in the range pH 5.5-9.0 and in the presence of up to 4 % (w/v) NaCl. The major cellular fatty acids were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 1omega9c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an uncharacterized amino-group containing polar lipid. The major quinone was ubiquinone 8 (Q-8) and the G+C content of the genomic DNA was 66.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XC21-2(T) formed a tight phylogenetic lineage with Pseudoxanthomonas dokdonensis KCTC 12543(T) within the genus Pseudoxanthomonas and was most closely related to P. dokdonensis KCTC 12543(T) and P. mexicana ATCC 700993(T), with 97.9 and 97.5 % 16S rRNA gene sequence similarity, respectively. On the basis of the unique physiological profile of the isolate and its phylogenetic divergence from known species, strain XC21-2(T) represents a novel species within the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas wuyuanensis sp. nov. is proposed. The type strain is XC21-2(T) ( = CGMCC 1.10978(T) = KCTC 23877(T)). PMID- 24215824 TI - Pelolinea submarina gen. nov., sp. nov., an anaerobic, filamentous bacterium of the phylum Chloroflexi isolated from subseafloor sediment. AB - A novel, anaerobic filamentous bacterium, strain MO-CFX1(T), was isolated from a methanogenic community, which was originally established from subseafloor sediments collected from off the Shimokita Peninsula, Japan. Cells were non-spore forming, non-motile, Gram-stain-negative and filamentous. The filaments were longer than 10 um and 130-150 nm in width. Growth of the strain was observed at 10-37 degrees C (optimum 25-30 degrees C), at pH 5.5-8.5 (optimum pH 7.0) and in 0-50 g NaCl l(-1) (optimum 15 g NaCl l(-1)). The strain was able to grow with a number of carbohydrates in the presence of yeast extract. The major cellular fatty acids were monounsaturated C18 : 1omega9, C16 : 1omega7 and saturated C18 : 0 and C16 : 0. The intact polar lipids of the strain were dominated by diacylglyceride and sphingolipid core lipid structures with monoglycosidic, mixed phosphomonoglycosidic and fatty-acid-modified monoglycosidic polar head groups. The G+C content of the genomic DNA was 52.4 mol%. Based on the comparative 16S rRNA gene sequence analysis, strain MO-CFX1(T) was affiliated with the class Anaerolineae within the phylum Chloroflexi and was most closely related to Leptolinea tardivitalis YMTK-2(T) (sequence identity of 91.0 %). Based on phenotypic and genetic properties of the novel isolate, we propose a novel species representing a new genus Pelolinea submarina gen. nov., sp. nov., for strain MO-CFX1(T) ( = JCM 17238(T), = KCTC 5975(T)). This is the first formal description, to our knowledge, of an isolate of the phylum Chloroflexi from the deep-sea sedimentary environment. PMID- 24215825 TI - Paenibacillus selenitireducens sp. nov., a selenite-reducing bacterium isolated from a selenium mineral soil. AB - A Gram-stain-positive, rod-shaped, facultatively anaerobic bacterium, designated strain ES3-24(T), was isolated from a selenium mineral soil. The isolate was endospore-forming, nitrate-reducing and motile by means of peritrichous flagella. The major menaquinone was menaquinone 7 (MK-7) and the predominant fatty acids (>5%) were anteiso-C15:0, iso-C16:0, C16:0 and anteiso-C17:0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and two unknown aminophospholipids. Strain ES3-24(T) contained meso-diaminopimelic acid in the cell-wall peptidoglycan and the DNA G+C content was 49.6 mol%. According to phylogenetic analysis based on the 16S rRNA gene sequence, strain ES3-24(T) was most closely related to Paenibacillus terrigena A35(T), with 16S rRNA gene sequence identity of 98.3%, while the other members of the genus Paenibacillus had 16S rRNA gene sequence identities of less than 95.0%. DNA-DNA relatedness between strain ES3-24(T) and P. terrigena CCTCC AB206026(T) was 39.3 %. In addition, strain ES3-24(T) showed obvious differences from closely related species in major polar lipids, nitrate reduction and other physiological and biochemical characteristics. The data from our polyphasic taxonomic study reveal that strain ES3-24(T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus selenitireducens sp. nov. is proposed. The type strain is ES3-24(T) ( = KCTC 33157(T) = CCTCC AB2013097(T)). PMID- 24215826 TI - Family participation during intensive care unit rounds: attitudes and experiences of parents and healthcare providers in a tertiary pediatric intensive care unit. AB - OBJECTIVE: To compare the experiences and attitudes of healthcare providers and parents regarding parental participation in morning rounds, in particular to evaluate for differences in perception of parental comprehension of rounds content and parental comfort with attendance, and to identify subgroups of parents who are more likely to report comfort with attending rounds. STUDY DESIGN: Cross-sectional survey of 100 parents and 131 healthcare providers in a tertiary care pediatric medical/surgical intensive care unit. Descriptive statistics were used to analyze survey responses; univariate and multivariate analyses were performed to compare parent and healthcare provider responses. RESULTS: Of parents, 92% reported a desire to attend rounds, and 54% of healthcare providers reported a preference for parental presence. There were significant discrepancies in perception of understanding between the 2 groups, with healthcare providers much less likely to perceive that parents understood both the format (30% vs 73%, P < .001) and content (21% vs 84%, P < .001) of rounds compared with parents. Analysis of parent surveys did not reveal characteristics correlated with increased comfort or desire to attend rounds. CONCLUSIONS: A majority of parents wish to participate in morning rounds, whereas healthcare provider opinions are mixed. Important discrepancies exist between parent and healthcare provider perceptions of parental comfort and comprehension on rounds, which may be important in facilitating parental presence. PMID- 24215828 TI - Clinical and radiographic evaluation of the cavus foot: surgical implications. AB - The key to successful management of the cavovarus foot is identifying the pathoanatomy and dysfunction that are driving the deformity and producing the symptoms. There is no substitute for a thorough clinical evaluation of the foot, evaluating the static alignment and dynamic function. Plain films alone are not sufficient to determine the diagnosis, but they are necessary for procedure selection and correction planning. This is especially true for assessing the degree of hindfoot varus. Some issues are difficult to diagnose, and imaging plays an important role. PMID- 24215827 TI - Knockdown of TrkA in cumulus oocyte complexes (COCs) inhibits EGF-induced cumulus expansion by down-regulation of IL-6. AB - Tyrosine kinase receptor A (TrkA), the high-affinity receptor of nerve growth factor (NGF), is known to play key roles in ovarian follicular development, such as assembly of early follicles and follicular ovulation. However, little is known about the roles of TrkA in cumulus oocyte complex (COC) expansion. In this study, we found that TrkA was abundant in large antral follicles and knockdown of TrkA in COCs attenuated epidermal growth factor (EGF)-induced COC expansion and further decreased the ovulation rate. The effect of TrkA on COC expansion was not mediated through downstream EGF effectors, phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) or drosophila mothers against decapentaplegic protein (SMAD), or through up-regulation of COC expansion-related transcripts such as prostaglandin-endoperoxide synthase 2 (Ptgs2), hyaluronan synthase 2 (Has2), TNF-induced protein 6 (Tnfaip6) or pentraxin 3 (Ptx3). However, pharmacological blockade of TrkA transducing activity (K252alpha) in COCs decreased the mRNA expression and protein secretion of interleukin-6 (IL-6), identified from mRNA microarray of K252alpha-treated COCs. Meanwhile, knockdown of IL-6 attenuated EGF-induced COC expansion. In addition, IL-6 rescued the inhibitory effect of K252alpha on EGF-induced cumulus expansion. Therefore, IL-6 may act as a new potential cumulus expansion-related transcript, which may be involved in the integration of TrkA and EGF signaling in affecting COC expansion. Here, we provide mechanistic insights into the roles of TrkA in EGF-induced cumulus expansion. Understanding potential cross-points between TrkA and EGF affecting cumulus expansion will help in the discovery of new therapeutic targets in ovulation-related diseases. PMID- 24215829 TI - The idiopathic cavus foot-not so subtle after all. AB - Idiopathic cavus deformity even in its mild form can result in several associated symptoms. Management of these symptoms without addressing the underlying biomechanical abnormality may result in failure of treatment. A careful clinical assessment is paramount. PMID- 24215830 TI - Treatment of ankle instability with an associated cavus deformity. AB - This article reviews the role of cavus in foot and ankle injury and summarizes the current surgical and nonsurgical treatments. Recognition of foot position is crucial in the management of ankle instability associated with cavovarus. Correcting foot alignment with orthoses or surgery improves the mechanics of the ankle, reducing the risk of instability and potentially delaying the onset of posttraumatic ankle arthritis. Progressive steps in the correction alignment are described, with technical tips and strategies for dealing with chronic instability. PMID- 24215831 TI - Joint-sparing correction for idiopathic cavus foot: correlation of clinical and radiographic results. AB - Adult cavovarus deformity patients present with rigid cavovarus deformity, where the correction can no longer be obtained using soft tissue procedures alone, and corrective arthrodesis or osteotomy must be performed to realign the deformity. Reconstructive surgeries for cavovarus foot deformities are variable and include hindfoot or midfoot osteotomy or arthrodesis, soft tissue release or lengthening, and tendon transfers. Recently adult cavovarus foot deformities have been more commonly addressed with joint preservation osteotomies and adjunctive soft tissue surgeries and less with triple arthrodesis. Clinical and radiographic outcomes are overall favorable. PMID- 24215832 TI - Joint sparing correction of cavovarus feet in Charcot-Marie-Tooth disease: what are the limits? AB - Charcot-Marie-Tooth disease is an inherited neuropathy that results in lower limb muscle imbalance and a resultant cavovarus deformity of the foot. With recognized poor outcomes of triple arthrodeses in the young patient, joint sparing surgery is preferred, which takes the form of osteotomies, soft-tissue releases, and tendon transfers to achieve a plantigrade and balanced foot. Due to the variability in muscle involvement and the presence of both mobile and fixed deformities, surgery must be individualized to each patient. PMID- 24215833 TI - What is the role of tendon transfer in the cavus foot? AB - Cavovarus deformity results from an imbalance of the foot's extrinsic musculature. Conditions leading to weakness of an isolated muscle result from nerve injury or sequelae of a compartment syndrome. When weakness of a muscle group presents, an underlying neurologic disorder must be suspected. Patients with hereditary sensory motor neuropathy present with a progressive pattern of imbalance and deformity. The deformity starts out flexible but becomes rigid over time. Rebalance muscle pull to realign the foot and ankle is important. Osteotomies and arthrodesis to realign the hindfoot will not maintain alignment as long as the agonist-antagonist pattern is not re-established. PMID- 24215834 TI - What is the role and limit of calcaneal osteotomy in the cavovarus foot? AB - Calcaneal osteotomy is a commonly used tool in cavovarus foot reconstructions. Understanding the indications and limitations of such an osteotomy is critical to success in reconstruction. We present a comprehensive review of surgical calcaneal osteotomy techniques and the currently available state of literature for their indications and limitations. PMID- 24215835 TI - Flexible cavovarus foot in children and adolescents. AB - Flexible cavovarus feet in children and adolescents can be challenging. A careful history and physical examination are paramount for determining the best treatment strategy and a multitude of options are available. Specific treatment strategies should be individualized and any bony correction must be in conjunction with a muscle balancing procedure. Well-timed soft tissue and occasionally bony procedures can delay the progression of deformity. These patients are monitored long term because further treatment may be required. PMID- 24215836 TI - Management of the rigid cavus foot in children and adolescents. AB - This article reviews historical approaches to the various osteotomies in the treatment of rigid cavus feet in children, with an emphasis on the biplanar nature of historical osteotomies. The Akron dome midfoot osteotomy is performed at the apex of the rigid cavus deformity and allows for maximum correction in any plane, and for varus, valgus, dorsal, plantar, and rotational correction. In that regard, the Akron dome midfoot osteotomy provides the greatest amount of multiplanar correction. It does not, however, provide correction of hindfoot deformities or deformity distal to the neck of the metatarsal. PMID- 24215837 TI - The indications and technique for surgical correction of pes cavus with external fixation. AB - Cavovarus is a deformity commonly associated with a variety of underlying disorders, and treatment of severe cavovarus foot with an underlying progressive disorder is very challenging. Often patients have undergone some prior surgery at least once, with increased potential risk of neurovascular injury and breakdown of soft tissue. In addition, concomitant problems such as torsional malalignment and leg-length discrepancy should also be addressed to prevent recurrence and treatment failure. In this article, indications and an algorithmic approach with various osteotomies for the treatment of cavovarus deformity using external fixation are discussed in detail. PMID- 24215838 TI - Arthrodesis for the cavus foot: when, where, and how? AB - When the cavus foot has become rigid, midfoot and triple arthrodesis may be the only reasonable surgical options left. The apex of the deformity is multiplanar and some deformities may have more than one apex. The best outcomes are achieved with minimal shortening of the foot, so correction should be by rotation and translation and with minimal wedge resection wherever possible. Posterior tibial tendon transfer and peroneus longus transfer are nearly always required for correction. If the principles of soft tissue balancing are followed, arthrodesis is an excellent procedure despite the literature that states to the contrary. PMID- 24215839 TI - The cavus foot. PMID- 24215841 TI - On the impoverishment of scientific education. AB - Hannah Arendt, one of the foremost political philosophers of the twentieth century, has argued that it is the responsibility of educators not to leave children in their own world but instead to bring them into the adult world so that, as adults, they can carry civilization forward to whatever challenges it will face by bringing to bear the learning of the past. In the same collection of essays, she discusses the recognition by modern science that Nature is inconceivable in terms of ordinary human conceptual categories - as she writes, 'unthinkable in terms of pure reason'. Together, these views on scientific education lead to an educational process that transforms children into adults, with a scientific adult being one who has the ability to conceptualize scientific systems independent of ordinary physical intuition. This article begins with Arendt's basic educational and scientific points and develops from them a critique of current scientific education in conjunction with an appeal to educate young scientists in a manner that allows them to fulfill their potential 'on the shoulders of giants'. While the article takes a general philosophical perspective, its specifics tend to be directed at biomedical education, in particular, how such education pertains to translational science. PMID- 24215840 TI - Activation of GILZ gene by photoactivated 8-methoxypsoralen: potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy. AB - Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL 10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL 12p70 production, demonstrating that GILZ is critical for this profile. PUVA induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects. PMID- 24215842 TI - Validation of miRNA-mRNA interactions by electrophoretic mobility shift assays. AB - BACKGROUND: MicroRNAs are small non-coding RNAs involved in gene expression regulation by targeting specific regions in the 3'-UTR of the mRNA of their target genes. This binding leads to a decrease in the protein levels of such genes either by mRNA degradation or mRNA destabilization and translation inhibition. The interaction between a miRNA and its target mRNAs is usually studied by co-transfection of a reporter expression vector containing the 3'-UTR region of the mRNA and an inhibitory or precursor molecule for the miRNA. This approach, however, does not measure the direct and physical interaction between a miRNA and a specific mRNA. FINDINGS: RNA molecules corresponding to miR-224 and to the 3'-UTR of SLC4A4 were incubated together and their interaction studied under different binding conditions using electrophoretic mobility shift assays. A direct and specific interaction between miR-224 and SLC4A4 mRNA was observed. This interaction was abolished in the presence of competitors. CONCLUSIONS: In this study, we explored a new application for the electrophoretic mobility shift assay and we demonstrated that it is a useful alternative method to assess, in a direct and specific manner, whether a miRNA binds to a specific predicted target mRNA. PMID- 24215844 TI - Occurrence and survival of synchronous pulmonary metastases in colorectal cancer: a nationwide cohort study. AB - OBJECTIVE: To investigate the occurrence of synchronous colorectal cancer metastases (SCCM) confined to the lungs, risk factors for these metastases and their impact on survival. METHODS: In a nationwide cohort study of 26,200 patients data were prospectively entered into the Danish Colorectal Cancer Group's (DCCG's) database between May 2001 and December 2011. The recorded data were merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable logistic- and extended Cox regression analyses were used to adjust for confounding variables. RESULTS: In total, 1970 patients (7.5%) had pulmonary SCCM of whom 736 (37%) had metastases exclusively in the lungs. Advanced age, recent years of diagnosis and a rectal index cancer were significantly associated with pulmonary SCCM. Adjustment for excess use of thoracic CT scans in rectal cancer patients did not alter this association (adjusted OR=1.81 (95% CI: 1.46-2.25, P<0.001)). Patients subjected to pulmonary metastasectomy, resection of primary tumour and chemotherapy had a superior overall survival compared with non-treated patients, especially when these therapeutic modalities were combined. CONCLUSIONS: The occurrence of pulmonary SCCM was higher than previously reported and had a severe impact on survival. Our analyses suggest that pulmonary metastasectomy, resection of the primary tumour and chemotherapy may be a sound strategy in patients with confined pulmonary SCCM, but the risk of selection bias and consequent exaggeration of the treatment effect should be kept in mind. This study may serve as a reliable un-biased reference for future evaluation on detection strategies and potential therapeutic interventions. PMID- 24215843 TI - Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease. AB - Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (alpha-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by alpha-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of alpha-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI) anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of alpha-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed. PMID- 24215845 TI - Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study. AB - AIM: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel. METHODS: Patients were randomised in a 2:1 ratio between IV brostallicin 10mg/m(2) and doxorubicin 75 mg/m(2) once every 3 weeks for a maximum of six cycles. Disease stabilisation at 26 weeks (primary end-point) was considered a 'success'. Further testing of brostallicin was warranted if >= 35 'successes' were observed in the first 72 eligible patients treated with brostallicin. In addition, patients were genotyped for glutathione S transferase (GST) polymorphisms. RESULTS: One hundred and eighteen patients were included (79 brostallicin and 39 doxorubicin). Brostallicin was well tolerated in comparison to doxorubicin with less grade 3-4 neutropenia (67% versus 95%), grade 2-3 systolic dysfunction (0% versus 11%), alopecia (17% versus 61%) and grade 2-3 mucositis (0% versus 18%). For brostallicin versus doxorubicin, 'successes' were observed in 5/77 versus 10/36, progression free survival at 1 year was 6.5% versus 15.6%, objective response rate was 3.9% versus 22.2% and overall survival at 1 year was 50.5% versus 57.9%, respectively. Only GSTA1 genotype was significantly associated with success rate of doxorubicin treatment. CONCLUSION: Brostallicin cannot be recommended at this dose and schedule in this patient population as first-line therapy. GSTA1 genotype may be predictive for doxorubicin efficacy but warrants further study. PMID- 24215846 TI - Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: results from the Danish Renal Cancer Group (DARENCA) study-2. AB - AIM: To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS: All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test. RESULTS: 1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P=0.0188); a significant increase in first line targeted therapy (22% versus 75%, P<0.0001); a significant increase in second line treatment (20% versus 40%, P=0.0104), a significant increased median OS (11.5 versus 17.2 months, P=0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55-0.99; P=0.0415), 2009 (HR 0.72, 95% CI, 0.54-0.96; P=0.0277) and 2010 (HR 0.63, 95% CI, 0.47-0.86; P=0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0-1 (HR 0.76, 95% CI, 0.58-0.99; P=0.0397) and performance status 2-3 (HR 0.19, 95% CI, 0.06 0.60; P=0.0051) were significantly associated with longer OS. CONCLUSION: This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients. PMID- 24215847 TI - The economic impact of cytoreductive surgery and tyrosine kinase inhibitor therapy in the treatment of advanced gastrointestinal stromal tumours: a Markov chain decision analysis. AB - PURPOSE: The current first-line treatment for patients with recurrent or metastatic gastrointestinal stromal tumours (GIST) is management with tyrosine kinase inhibition (TKI). There is an undefined role for surgery in the management of these patients. This study uses a cost analysis to examine the economic impact of treating patients with TKI in combination with surgery at different time points in their treatment trajectories. METHODS: A Markov chain decision analysis was modelled over a 2-year time horizon to determine costs associated with surgery in combination with imatinib mesylate (IM) or sunitinib malate (SU) in seven scenarios varied by TKI agent, dose and disease status (stable versus localised progressive disease). Rates of disease progression, surgical morbidity, mortality and adverse drug reactions were extracted from the existing literature. Deterministic sensitivity analyses were performed to examine changes in cost due to variations in key variables. RESULTS: The least-costly scenario was to perform no surgery. The most costly scenario was to perform surgery on patients with localised progressive disease on IM 800 mg. The overall range of costs clustered within approximately $47,000 (USD). Variations in surgical cost, surgical mortality and cost of IM demonstrated thresholds for changing the least-costly scenario within plausible tested ranges. CONCLUSION: Costs of surgical intervention at different time-points within the treatment course of patients with advanced GIST fluctuate within a relatively narrow range, suggesting that costs arise primarily from the administration of TKI. The decision to pursue cytoreductive surgery should not be based on cost alone. Future studies should incorporate health-state utilities when available. PMID- 24215848 TI - The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study. AB - BACKGROUND: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. METHODS: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. RESULTS: The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95% confidence interval [CI], $135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to $149,455 (95% CI, $100,356 to $245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95% CI, $106,703 to $233,225). CONCLUSIONS: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial. PMID- 24215849 TI - The use of diplopods in soil ecotoxicology - a review. AB - Diplopods play an important role in the dynamics of terrestrial ecosystems, actively participating in the decomposition of organic matter and soil aeration. They have gained increased attention from ecotoxicology research because they are continuously exposed to soil contaminants and biological effects of chemical stressors can be measurable at various levels of biological organization. This paper is the first review on the use of diplopods as soil bioindicators and compiles the effects of the different toxic chemical agents on these animals. Special emphasis is given on the interpretation of the effects of heavy metals and complex mixtures in target organs of diplopods. PMID- 24215850 TI - Misoprostol for intrauterine device insertion in nulliparous women: a randomized controlled trial. AB - OBJECTIVE: To examine the effects of preprocedure misoprostol on intrauterine device (IUD) placement in nulliparous women. STUDY DESIGN: In this randomized controlled double-blind trial at the University of New Mexico reproductive health clinic, nulliparous women requesting an IUD were randomized to 400 mcg of buccal misoprostol or placebo 2-8 hours before insertion. Primary outcomes included pain on a 10-cm visual analog scale and women's perception of the value of delaying insertion for an effective medication. Provider ease of insertion and need for adjunctive insertion measures were also assessed, on a visual analog scale. Participants indicated maximum pain after IUD insertion, pain level they would tolerate to avoid delay in IUD insertion, and preference for IUD insertion without delay if an effective medication was available. RESULTS: Of 85 women enrolled, 3 were ineligible; 42 were randomized to misoprostol and 40 to placebo. There were no differences between groups in worst insertion pain, (5.8 +/- 2.0 vs 5.9 +/- 2.0, P = .94), provider ease of insertion (2.2 +/- 2.2 vs 2.5 +/- 2.2; P = .54) or adjunctive measures (14% vs 25%; P = .27). The groups were willing to tolerate the same mean pain (4.9 +/- 2.5 vs 5.7 +/- 2.4, P = .18) to avoid waiting for medication. The majority of women (85%) preferred to wait for an effective medication. CONCLUSION: Misoprostol for nulliparous women did not decrease pain or improve the ease of insertion of an IUD. Most women were willing to wait for a medication that decreases pain, indicating a need to pursue alternatives for pain control with IUD insertion. PMID- 24215851 TI - Serum leptin levels and reproductive function during the menstrual cycle. AB - OBJECTIVE: The purpose of this study was to investigate the role of leptin on reproductive hormones and ovulation. STUDY DESIGN: The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for <=2 menstrual cycles (n = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone, and testosterone were measured <=8 times per cycle. The association of time-varying leptin and reproductive hormones over the cycle was estimated with the use of linear mixed models that were adjusted for percent body fat and age with inverse probability weighting for time-varying physical activity, caloric intake, and other reproductive hormones. The odds ratio for sporadic anovulation (n = 42 cycles) was estimated with the use of generalized linear models that were adjusted for percent body fat and age. RESULTS: Geometric mean serum leptin levels increased from menses to the late luteal phase (16.7-20.4 ng/mL; P < .01), with a mid-cycle peak (21.7 ng/mL) at the time of the LH surge (P < .01). A 10% higher leptin level across the menstrual cycle was associated with higher estradiol levels (2.2%; 95% CI, 1.5-3.0), luteal progesterone levels (2.1%; 95% CI, 0.5-3.7), ovulatory LH levels (1.2%; 95% CI, 0-2.3), testosterone levels (0.6%; 95% CI, 0.3 0.9), and lower follicle-stimulating hormone levels (-0.7%; 95% CI, -1.1 to 0.4). Leptin at the time of the expected LH surge was moderately inversely associated with sporadic anovulation (per log increase in leptin; adjusted odds ratio, 0.58; 95% CI, 0.28-1.22). CONCLUSION: The association that was observed between leptin level and reproductive function points to a possible relationship between serum leptin level and enhanced fertility. PMID- 24215852 TI - The influence of maternal body mass index on fetal weight estimation in twin pregnancy. AB - OBJECTIVE: Sonographic estimated fetal weight (EFW) is important in the management of high-risk pregnancies. The possibility that increased maternal body mass index (BMI) adversely affects EFW assessments in twin pregnancies is controversial. The aim of this study was to investigate the effect of maternal BMI on the accuracy of EFW assessments in twin gestations prospectively recruited for the ESPRiT (Evaluation of Sonographic Predictors of Restricted growth in Twins) study. STUDY DESIGN: One thousand one twin pair pregnancies were recruited. After exclusion, BMI, birthweights, and ultrasound determination of EFW (within 2 weeks of delivery) were available for 943 twin pairs. The accuracy of EFW determination was defined as the difference between EFW and actual birthweight for either twin (absolute difference and percent difference). Cells with less than 5% of the population were combined for analysis resulting in the following 3 maternal categories: (1) normal/underweight, (2) overweight, and (3) obese/extremely obese. RESULTS: Analysis of the 3 categories revealed mean absolute variation values of 184 g (8.0%) in the normal/underweight group (n = 531), 196 g (8.5%) in the overweight group (n = 278), and 206 g (8.6%) in the obese/extremely obese group (n = 134) (P = .028, which was nonsignificant after adjustment for multiple testing). Regression analysis showed no linear or log linear relationship between BMI and the accuracy of EFW (P value for absolute difference = .11, P value for percentage difference = .27). CONCLUSION: Contrary to a commonly held clinical impression, increasing maternal BMI has no significant impact on the accuracy of EFW in twin pregnancy. PMID- 24215853 TI - Ultrasound assessment of uterine cavity remodeling after surgical correction of subseptations. AB - OBJECTIVE: To assess the postoperative restoration of a normal uterine cavity, uterine cavity measurements were obtained in patients with arcuate or septate uteri in the periods before and after resection. STUDY DESIGN: Twenty-eight women diagnosed with arcuate or septate uteri were evaluated with 3-dimensional ultrasound before and after undergoing surgical resection by hysteroscopic resection, in a university center. In addition to the conventional parameters, measurements of the subseptum's length and width, and cavity width, were obtained on a frozen coronal view of the uterus. Postoperatively, uterine cavity width was measured. RESULTS: Twelve patients were diagnosed with arcuate uterus and 16 with septate uterus and subsequently underwent surgical correction. Of them, 50% had a retroverted uterus and 61% had a diagnosis of polycystic ovary syndrome (7/28, or 25%, had both). Uterine length, width, and height, before and after resection, were similar between arcuate and septate, as were the subsepti base widths, despite the different lengths. However, cavity width was significantly decreased after resection only in the septate uterus group: 3.6 cm, 95% confidence interval, 3.3-3.9, preoperatively vs 2.8 cm, 95% confidence interval, 2.5-3.1, postoperatively, respectively; P < .001. The postoperative difference in cavity width was directly correlated with the length of the subseptation (r -0.59, P = .05). CONCLUSION: Postoperative measurements of the uterine cavity revealed a remarkable uterine remodeling capacity: we speculate this could represent the most important single change to explain improved pregnancy outcomes after surgical correction of subseptations. PMID- 24215854 TI - Birth by vacuum extraction delivery and school performance at 16 years of age. AB - OBJECTIVE: The aim of the present study was to investigate cognitive competence, as indicated by school performance, at 16 years of age, in children delivered by vacuum extraction. STUDY DESIGN: This was a register study of a national cohort of 126,032 16 year olds born as singletons, with a vertex presentation, at a gestational age of 34 weeks or older, with Swedish-born parents, delivered between 1990 and 1993 without major congenital malformations. Linear regression was used to analyze mode of delivery in relation to mean scores from national tests in mathematics (40.2; scale, 10-75; SD, 14.9) and mean average grades (223.8; scale, 10-320; SD, 52.3), with adjustment for perinatal and sociodemographic confounders. RESULTS: Children delivered by vacuum extraction ( 0.51; 95% confidence interval [CI], -0.76 to 0.26) as well as by nonplanned cesarean section (-0.51; 95% CI, -0.82 to -0.20) had slightly lower mean mathematics test scores than children born vaginally without instruments, after adjustment for major confounders. Mean average grades in children delivered by vacuum extraction were -1.05 (95% CI, -1.87 to -0.23) and -1.20 (95% CI,-2.24 to 0.16) in children delivered by nonplanned cesarean section compared with children born vaginally. CONCLUSION: Children delivered by vacuum extraction had slightly lower grades at age 16 years compared with those born by noninstrumental vaginal delivery but very similar to those delivered by nonplanned cesarean. This suggests that vacuum extraction and nonplanned cesarean are equivalent alternatives for terminating deliveries with respect to cognitive outcomes. PMID- 24215855 TI - Recurrence of ovarian endometrioma after second-line, conservative, laparoscopic cyst enucleation. AB - OBJECTIVE: We sought to evaluate the cumulative recurrence rate of endometrioma after a second-line, conservative, laparoscopic endometriotic cyst enucleation and to analyze the factors that influence the recurrence of endometrioma. STUDY DESIGN: A multicenter retrospective cohort study was performed at 3 gynecologic surgery centers from January 2000 through December 2010. Patients surgically treated by laparoscopic enucleation of endometriotic cysts on 2 previous occasions were selected. All patients were aged <40 years at the time of the primary surgery and were followed up for at least 6 months. Endometrioma recurrence was considered when transvaginal sonography indicated a cystic mass with a diameter of >=20 mm. RESULTS: In total, 183 patients were followed up for 33.2 +/- 27.7 months (range, 6-121 months). Thirty-eight (20.8%) patients experienced recurrence after the second-line surgery and 24 (13.1%) patients underwent a third surgery. The median time to recurrence was 24 +/- 3.36 months (SEM) (range, 3-72 months). The cumulative recurrence rates per patient at 12, 24, 36, and 60 months after the second-line surgery were 7.7%, 13.7%, 21.3%, and 37.5%, respectively. After multivariate analysis and analysis of covariance, the revised American Fertility Society score and stage were significantly higher in patients who experience a third recurrence of endometrioma. CONCLUSION: The cumulative recurrence rate of ovarian endometrioma after a second-line surgery appears to be correlated to the duration of follow-up. Severe endometriosis at the second-line surgery seems to be a factor associated with a high recurrence risk. Physicians should be cautious with regard to the postoperative management of these patients. PMID- 24215856 TI - Interpregnancy body mass index change and success of term vaginal birth after cesarean delivery. AB - OBJECTIVE: We investigated the effect of interpregnancy body mass index (BMI) change on success of term vaginal birth after cesarean (VBAC) among normal, overweight and obese women. STUDY DESIGN: Using 1992-2009 Washington State birth certificate data linked with hospitalization records, we conducted a population based retrospective cohort study of nulliparous women (BMI >=18.5 kg/m(2)) with a primary cesarean in their first birth and a term trial of labor in their second. Interpregnancy weight change (difference between first and second prepregnancy BMIs) was categorized as maintenance (<1 BMI unit change), loss (>=1 unit), moderate gain (>=1 and <2 units), high gain (>=2 units). We estimated relative risks of VBAC success using generalized linear models with a log-link function, adjusting for maternal age, race/ethnicity, nativity, marital status, education, smoking, primary cesarean indication, interpregnancy interval, birth year for second birth, and prenatal care adequacy. RESULTS: Among 8302 women who attempted a term trial of labor, 65% had a successful VBAC. Women with normal BMI before their first pregnancy experienced an 8% decrease in VBAC success with moderate gain (relative risk [RR], 0.92; 95% confidence interval [CI], 0.87-0.98) and a 12% decrease in success with high gain (RR, 0.88; 95% CI, 0.83-0.93), compared with normal weight women who maintained weight. Weight loss increased VBAC success in women who were overweight (RR, 1.12; 95% CI, 1.01-1.25) or obese before their first delivery (RR, 1.24; 95% CI, 1.04-1.49), compared with overweight and obese women, respectively, who maintained weight. CONCLUSION: Women can improve their chance of successful VBAC through interpregnancy weight management. PMID- 24215857 TI - Impaired steroidogenesis and apoptosis of granulosa-luteal cells in primary culture induced by cis-platinum. AB - OBJECTIVE: The purpose of this study was to test the hypothesis that the cytotoxic drug cis-platinum (CP) induces premature ovarian failure by reducing the viability of human granulosa cells. STUDY DESIGN: We incubated cultured human granulosa-luteal cells (GLCs) with varying concentrations of CP for 48 hours. Steroidogenesis and apoptosis were assessed by progesterone and estradiol, annexin V/propidium iodide, phase contrast, and transmission electron microscopy. RESULTS: CP caused impaired production of progesterone and estradiol in a dose- and a time-dependent fashion. The estradiol production was more pronounced than progesterone for each concentration of CP that was studied. The phase contrast microscopy of CP-treated GLCs showed loss of cell number with condensed nuclei. CP-induced apoptosis was maximum at 20 MUg/mL compared with a 10-MUg/mL concentration (79.9% +/- 4.6% vs 58.3% +/- 3.9%; P < .01). The hallmark of apoptosis (ie, nuclear condensation, cell size shrinkage) was seen in CP-treated cells by transmission electron microscopy. CONCLUSION: CP induces apoptosis of human GLCs in culture with impaired steroidogenesis, which may be one mechanism by which a CP-containing regime induces premature ovarian failure. PMID- 24215858 TI - Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements. AB - OBJECTIVE: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. STUDY DESIGN: We conducted a 12-week 3 * 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). RESULTS: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). CONCLUSION: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect. PMID- 24215860 TI - Bile acids in a multicenter, population-based case-control study of stillbirth. AB - OBJECTIVE: We sought to compare bile acids in women with and without stillbirth in a population-based study. STUDY DESIGN: The Stillbirth Collaborative Research Network conducted a multisite, population-based case-control study of stillbirth (fetal deaths >=20 weeks). Maternal sera were obtained at the time of enrollment and frozen at -80 degrees C until assay for bile acids. RESULTS: Assays were performed in 581 women with stillbirth and 1546 women with live births. Bile acid levels were slightly higher in women with stillbirth (geometric mean [95% confidence interval {CI}] = 3.2 [3.0-3.5]) compared to live births (2.9 [2.7 3.1], P = .0327). However, the difference was not significant after adjustment for baseline risk factors for stillbirth. The proportion of women with elevated levels (>=10 or >=40 MUmol/L) was similar in stillbirths and live births. Results were similar when the analysis was limited to subsets of stillbirths and live births. In women with stillbirths not associated with fetal anomalies or obstetric complications bile acid levels were higher than in women with term live births (geometric mean [95% CI] = 3.4 [3.0-3.8] vs 2.9 [2.7-3.0], P = .0152, unadjusted; P = .06, adjusted). However, a similar proportion of women in both groups had levels >=10 MUmol/L (10.7 vs 7.2%; odds ratio [OR], 1.54; 95% CI, 0.97 2.44; adjusted OR, 1.29; 95% CI, 0.78-2.15) and >=40 MUmol/L (1.7 vs 0.7%; OR, 2.58; 95% CI, 0.85-7.84; adjusted OR, 2.28; 95% CI, 0.79-6.56). CONCLUSION: Our data do not support testing for bile acids in cases of stillbirth in the absence of clinical evidence of intrahepatic cholestasis of pregnancy. PMID- 24215861 TI - Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes. AB - OBJECTIVE: To assess angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the Ang 1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes, and their predictive accuracy. STUDY DESIGN: This cohort study measured serum Ang-1 and Ang-2 levels in 4785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks, and stillbirth). RESULTS: Median (interquartile range) levels for Ang-1, Ang-2, and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/mL (13.6 26.4), 15.5 ng/mL (10.3-22.7), and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth, and socioeconomic status significantly affected Ang-1, Ang-2, and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (<10th percentile) and high Ang-1/Ang-2 ratio (>90th percentile) had increased risk of developing most adverse pregnancy outcomes. Compared with the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage (Ang-1/Ang-2 ratio area under receiver operating characteristic curve = 0.70; maternal risk factors = 0.58). Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. CONCLUSION: Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information. PMID- 24215859 TI - Association of cord blood digitalis-like factor and necrotizing enterocolitis. AB - OBJECTIVE: Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport, and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC). STUDY DESIGN: Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for EDLF using a red cell Rb(+) uptake assay in which the inhibition of sodium pump-mediated Rb(+) transport was used as a functional assay of EDLF. Specimens were assayed blinded to neonatal outcome. Cases (NEC, n = 25) and controls (neonates not developing stage 2 or 3 NEC, n = 24) were matched by study center and gestational age. None of the women had preeclampsia. Cases and controls were compared using the Wilcoxon test for continuous and the Fisher exact test for categorical variables. A conditional logistic regression analysis was used to assess the odds of case vs control by EDLF level. RESULTS: Cases and controls were not significantly different for gestational age, race, maternal steroid use, premature rupture of membranes, or MgSO4 treatment. In logistic models adjusted for treatment group, race, premature rupture of membranes, and gestational age, cord sera EDLF was significantly associated with development of NEC (P = .023). CONCLUSION: These data demonstrated an association between cord sera EDLF and NEC. PMID- 24215862 TI - Lactose autoinduction with enzymatic glucose release: characterization of the cultivation system in bioreactor. AB - The lactose autoinduction system for recombinant protein production was combined with enzymatic glucose release as a method to provide a constant feed of glucose instead of using glycerol as a carbon substrate. Bioreactor cultivation confirmed that the slow glucose feed does not prevent the induction by lactose. HPLC studies showed that with successful recombinant protein production only a very low amount of lactose was metabolized during glucose-limited fed-batch conditions by the Escherichia coli strain BL21(DE3)pLysS in well-aerated conditions, which are problematic for glycerol-based autoinduction systems. We propose that slow enzymatic glucose feed does not cause a full activation of the lactose operon. However recombinant PDI-A protein (A-domain of human disulfide isomerase) was steadily produced until the end of the cultivation. The results of the cultivations confirmed our earlier observations with shaken cultures showing that lactose autoinduction cultures based on enzymatic glucose feed have good scalability, and that this system can be applied also to bioreactor cultivations. PMID- 24215864 TI - Soluble production of a biologically active single-chain antibody against murine PD-L1 in Escherichia coli. AB - Programmed death ligand 1 (PD-L1), is an important regulator of T-cell activation and has emerged as an important target for cancer immunotherapy. Single chain variable fragments (scFvs) have several desirable characteristics and are an attractive alternative to monoclonal antibodies for experimental or therapeutic purposes. Three chickens were immunized against murine PD-L1, and mRNA isolated from their spleens was used to generate an immunized immunoglobulin variable region library. Using splice-overlap extension PCR, variable region cDNAs were combined to generate full-length scFvs. M13 phage display of the resulting scFv library identified a functional scFv against PD-L1 (alphaPD-L1 scFv). The scFv was expressed as soluble protein in the periplasm and culture supernatant of recombinant Escherichia coli and purified with a 6*-His tag using immobile metal affinity chromatography. The dissociation constant of alphaPD-L1 scFv was determined to be 7.11*10(-10)M, and the scFv demonstrated inhibitory biological activity comparable to an antagonistic monoclonal antibody, providing an alternative agent for blocking PD-1/PD-L1 signaling. PMID- 24215865 TI - Neurological complications of infective endocarditis: new breakthroughs in diagnosis and management. AB - Neurological complications are frequent in infective endocarditis (IE) and increase morbidity and mortality rates. A wide spectrum of neurological disorders may be observed, including stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left sided abnormalities of native or prosthetic valves. Ischemic lesions account for 40% to 50% of IE central nervous system complications. Systematic brain MRI may reveal cerebral abnormalities in up to 80% of patients, including cerebral embolism in 50%, mostly asymptomatic. Neurological complications affect both medical and surgical treatment and should be managed by an experimented multidisciplinary team including cardiologists, neurologists, intensive care specialists, and cardiac surgeons. Oral anticoagulant therapy given to patients presenting with cerebral ischemic lesions should be replaced by unfractionated heparin for at least 2 weeks, with a close monitoring of coagulation tests. Recently published data suggest that after an ischemic stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Surgery should be postponed for 2 to 3 weeks for patients with intracranial hemorrhage. Endovascular treatment is recommended for cerebral mycotic aneurysms, if there is no severe mass effect. Recent data suggests that neurological failure, which is associated with the location and extension of brain injury, is a major determinant for short-term prognosis. PMID- 24215863 TI - Developments in purification methods for obtaining and evaluation of collagen derived endogenous angioinhibitors. AB - Collagen constitutes one of the vital components of the basement membrane scaffolds. Non-collagenous domains (NC1) derived from collagens exhibit potent anti-angiogenic properties, thus attaining significance in regulation of angiogenesis promoted diseases. Individual NC1 domains essential for anti angiogenic evaluations are generally obtained through purification of individual non-collagenous domains, which have undergone steady developments for enhancing the yields, purpose of biological evaluations and solubility based on the nature of different NC1 domains. This review focuses on the method developments in obtaining biologically active NC1 domains and for specific evaluations in different scenarios. PMID- 24215866 TI - Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties. AB - Tumor cells have the ability to exploit stromal cells to facilitate metastasis. By using malignant melanoma as a model, we show that the stroma adjacent to metastatic lesions is enriched in the known metastasis-promoting protein S100A4. S100A4 stimulates cancer cells to secrete paracrine factors, such as inflammatory cytokines IL8, CCL2 and SAA, which activate stromal cells (endothelial cells and monocytes) so that they acquire tumor-supportive properties. Our data establishes S100A4 as an inducer of a cytokine network enabling tumor cells to engage angiogenic and inflammatory stromal cells, which might contribute to pro metastatic activity of S100A4. PMID- 24215867 TI - Targeted therapy against chemoresistant colorectal cancers: Inhibition of p38alpha modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FoxO3A. AB - Chemoresistance is a major obstacle to effective therapy against colorectal cancer (CRC) and may lead to deadly consequences. The metabolism of CRC cells depends highly on the p38 MAPK pathway, whose involvement in maintaining a chemoresistant behavior is currently being investigated. Our previous studies revealed that p38alpha is the main p38 isoform in CRC cells. Here we show that p38alpha pharmacological inhibition combined with cisplatin administration decreases colony formation and viability of cancer cells and strongly increases Bax-dependent apoptotic cell death by activating the tumor suppressor protein FoxO3A. Our results indicate that FoxO3A activation up-regulates transcription of its target genes (p21, PTEN, Bim and GADD45), which forces both chemosensitive and chemoresistant CRC cells to undergo apoptosis. Additionally, we found that FoxO3A is required for apoptotic cell death induction, as confirmed by RNA interference experiments. In animal models xenografted with chemoresistant HT29 cells, we further confirmed that the p38-targeted dual therapy strategy produced an increase in apoptosis in cancer tissue leading to tumor regression. Our study uncovers a major role for the p38-FoxO3A axis in chemoresistance, thereby suggesting a new therapeutic approach for CRC treatment; moreover, our results indicate that Bax status may be used as a predictive biomarker. PMID- 24215868 TI - Poly (ADP-ribose) polymerase inhibitor LT-626: Sensitivity correlates with MRE11 mutations and synergizes with platinums and irinotecan in colorectal cancer cells. AB - Some colorectal cancers (CRC) display microsatellite instability (MSI) leading to mutations in genes such as MRE11. The aim of this study was to determine whether MSI or MRE11 mutational status correlates with sensitivity to the PARP inhibitor LT-626 and whether LT-626 synergizes with DNA-damaging chemotherapeutic agents. CRC cells harboring biallelic MRE11 mutations were more sensitive to LT-626 and stable overexpression or knock-down of MRE11 in cell lines correlated with sensitivity. Synergism was evident between LT-626 and cisplatin, oxaliplatin and SN-38 suggesting that PARP inhibitors in combination with DNA damaging agents may be a successful strategy for treatment of CRC. PMID- 24215869 TI - Aneurysm formation associated with ionizing radiation. PMID- 24215870 TI - A balanced perspective on the role of endoscopy in the surgical management of trigeminal neuralgia. PMID- 24215871 TI - Functional pituitary adenoma recurrence after surgical resection. PMID- 24215872 TI - Genome-wide association studies of common obesity: now and future. PMID- 24215874 TI - Serum 25(OH)D and lipid levels in Chinese obese and normal weight males before and after oral vitamin D supplementation. AB - OBJECTIVE: To study the effect of oral vitamin D (VD) supplementation on VD status and serum lipid in Chinese obese and healthy normal-weight men. METHODS: Twenty-one obese men with their body mass index (BMI)>28 kg/m(2) served as an obese group and 22 healthy normal-weight men with their BMI<24 kg/m(2) served as a control group in this study. After they were given 50 000 IU of oral VD, once a week for 8 weeks, the serum 25-hydroxyvitamin D [25(OH)D] concentration was measured with an enzyme-immunoassay kit. RESULTS: After oral VD supplementation, the serum 25(OH)D concentration significantly increased from 46.1+/-9.1 nmol/L to 116.7+/-20.3 nmol/L in the obese subjects (P<0.01) and from 52.8+/-17.8 nmol/L to 181.3+/-30.2 nmol/L in the control ones (P=0.13). The serum high-density lipoprotein cholesterol (HDL-C) level was reduced within the normal reference range in the obese group. However, no significant change was observed in the level of other serum lipids (triglycerides, total cholesterol, and low-density lipoprotein cholesterol) in either of the two groups. CONCLUSION: The effect of high-dose oral VD supplementation is weaker on VD status in the obese group than in the control group. High-dose oral VD supplementation has no side effect on serum lipid level in obese and control groups. PMID- 24215873 TI - Relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease among people in Inner Mongolia of China. AB - OBJECTIVE: To explore the relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease (CVD). METHODS: Blood pressure, body weight, body height, waist circumference and lifestyle risk factors were measured and studied among 2589 participants in Inner Mongolia of China, and biomarkers of inflammation and endothelial dysfunction including high-sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II were investigated. RESULTS: Subjects with metabolic risk factors for CVD had higher levels of hsCRP, sE selectin and sICAM-1 than those without such risk factors (all P<0.05). Levels of all biomarkers positively and significantly increased with aggregation of the metabolic risk factors among the subjects (all P for trend <0.001). Data from the multivariate analysis showed that participants with high levels of hsCRP [odds ratio (OR): 1.96, 95% confidence interval (CI): 1.52-2.53], sE-selectin (OR: 1.35, 95% CI: 1.05-1.72), and angiotensin II (OR: 1.81, 95% CI: 1.40-2.33) were more likely to develop hypertension; participants with high levels of hsCRP (OR: 2.33, 95% CI: 1.85-2.94), sE-selectin (OR: 1.24, 95% CI: 1.00-1.54), and sICAM-1 (OR: 1.70, 95% CI: 1.30-2.22) were more likely to develop dyslipidemia, and those with high levels of hsCRP (OR: 2.95, 95% CI: 2.27-3.83) and sICAM-1(OR: 2.80, 95% CI: 2.06-3.80) were more likely to develop hyperglycemia. CONCLUSION: Biomarkers of inflammation and endothelial dysfunction were separately associated with relevant metabolic risk factors for CVD. And appropriate measures should be taken to control inflammation and improve endothelial function among individuals with different metabolic risk factors for CVD. PMID- 24215875 TI - Quantitative study of iron metabolism-related genes expression in rat. AB - OBJECTIVE: To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues. METHODS: Two groups (n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR. RESULTS: After 4 weeks, the hemoglobin (Hb) level and red blood cell (RBC) count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney. CONCLUSION: Findings from our study provides new understandings about the relative expression, regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2, divalent metal transporter 1, ferritin, iron regulation proteins 1 and 2, hereditary hemochromatosis protein, hepcidin, ferroportin 1 and hephaestin in intestine, liver, spleen, kidney, heart, and lung of rat. PMID- 24215876 TI - Mitochondrial modulation of apoptosis induced by low-dose radiation in mouse testicular cells. AB - OBJECTIVE: To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells. METHODS: Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase (T-NOS) and Na+/K+ ATPase activities were biochemically assayed. Reactive oxygen species (ROS) and mitochondrial membrane potential (Deltapsim) were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) were quantified by real-time reverse-transcription PCR (RT-PCR). Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. RESULTS: LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na+/K+ ATPase activity and mitochondrial Deltapsim, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase 3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. CONCLUSION: LDR can induce testicular cell apoptosis through mitochondrial signaling pathways. PMID- 24215877 TI - Plasticity of regulation of mannitol phosphotransferase system operon by CRP-cAMP complex in Vibrio cholerae. AB - OBJECTIVE: The complex of the cyclic AMP receptor protein (CRP) and cAMP is an important transcriptional regulator of numerous genes in prokaryotes. The transport of mannitol through the phosphotransferase systems (PTS) is regulated by the CRP-cAMP complex. The aim of the study is to investigate how the CRP-cAMP complex acting on the mannitol PTS operon mtl of the Vibrio cholerae El Tor biotype. METHODS: The crp mutant strain was generated by homologous recombination to assess the need of CRP to activate the mannitol PTS operon of V. cholerae El Tor. Electrophoretic mobility shift assays (EMSA) and the reporter plasmid pBBRlux were used to confirm the role that the CRP-cAMP complex playing on the mannitol PTS operon mtl. RESULTS: In this study, we confirmed that CRP is strictly needed for the activation of the mtl operon. We further experimentally identified five CRP binding sites within the promoter region upstream of the mannitol PTS operon mtl of the Vibrio cholerae El Tor biotype and found that these sites display different affinities for CRP and provide different contributions to the activation of the operon. CONCLUSION: The five binding sites collectively confer the strong activation of mannitol transfer by CRP in V. cholerae, indicating an elaborate and subtle CRP activation mechanism. PMID- 24215878 TI - Magnetic resonance imaging and histopathological analysis of experimental muscle injuries in a rabbit. AB - OBJECTIVE: To investigate the correlation of magnetic resonance imaging (MRI) with histopathological changes, and to evaluate T2 mapping in assessing muscle trauma in a rabbit model of muscle injury. METHODS: We divided 35 rabbits into seven groups that each represented a different time point after intramuscular hemorrhage and muscle injury. Hemorrhage was created by injecting autologous blood into the left legs, and muscle injury was created by scalpel incision of the biceps femoris of the right legs. At different time points, the rabbits underwent T1-weighted imaging and T2-weighted imaging (T1WI and T2WI) and T2 mapping. T2 relaxation times were measured, and the corresponding samples were evaluated for pathological changes RESULTS: After 2 h, the intramuscular hemorrhage model demonstrated an increased signal intensity on both T1WI and T2WI. Histological examination showed erythrocytes within the muscle bundle. On days 1 and 3, the MRI signals were decreased, and there were no significant changes after day 7. From 2 h to 3 days, the muscle-injury model showed a high signal on both T1WI and T2WI. Corresponding pathological changes included rupture and edema of muscle fibers, and inflammation. The abnormal signals were reduced on day 7. After day 14, the T2WI intensity remained high. T1WI showed no abnormal changes, but some models showed a high signal, representing fresh bleeding and fatty tissue. T2 relaxation times were significantly different between the central and marginal regions, and between the marginal and normal regions. CONCLUSION: MRI clearly demonstrates intramuscular hemorrhage and muscle injury, which correlate well with histopathological changes. T2 mapping is useful in assessing the extent of injury. PMID- 24215879 TI - Association of metabolic syndrome with inflammation in Chinese adults with different kidney function. PMID- 24215880 TI - Pedestrian mortality between 2006 and 2010 in China: findings from non-police reported data. AB - Pedestrian safety in China is an important but largely neglected issue, in part due to the substantial under-reporting within police data. In this study we aimed to examine changes in pedestrian fatality between 2006 and 2010 in China using non-police reported data. A multi-year study was conducted based on the mortality data during 2006-2010 from the Disease Surveillance Points (DSP) data in China. Between 2006 and 2010, the crude pedestrian mortality increased from 7.0 to 10.5 per 100 000 populations. Annual pedestrian mortality from DSP data was 13 times in 2006 and 55 times in 2010 mortality for pedestrians and passengers from police reported data in the corresponding years. After controlling for sex, age, and urban/rural, the mortality increased by 44% from 2006 to 2010 (adjusted mortality rate ratio (MRR)=1.11, 95% CI 1.10-1.12). The problem of pedestrian deaths is much more serious in China than that officially reported by the police. Significant and urgent efforts are needed to save lives of pedestrian in China. PMID- 24215881 TI - Diurnal temperature range and daily emergency room admissions among the elderly in Beijing, China. PMID- 24215882 TI - Cronobacter carriage in neonate and adult intestinal tracts. AB - A total of 7 Cronobacter strains were isolated from 703 fecal samples collected in Jinan from June 13 to December 30, 2011, with the positive rate of Cronobacter spp. being 1.0% (95% confidence interval 0.6%-1.4%). Three Cronobacter sakazakii stains were isolated from 157 fecal samples of healthy neonates (95% confidence interval 0.4%-5.5%). This number was slightly higher than that isolated from 273 fecal samples of healthy adults, in which 1 strain of C. sakazakii and 1 strain of Cronobacter malonaticus were isolated, and that from 173 fecal samples of adults with acute diarrhea, in which 1 strain of C. sakazakii and 1 strain of C. malonaticus were isolated, but the differences were not statistically significant (P>0.05). The Cronobacter isolates were all from different genetic sources. It should be noted that Cronobacter carriage may cause infection under certain conditions, especially in neonates. PMID- 24215883 TI - Inactivation and regrowth of antibiotic-resistant bacteria by PAA disinfection in the secondary effluent of a municipal wastewater treatment plant. AB - Inactivation and microbial regrowth of penicillin-, ampicillin-, cefalexin-, tetracycline-, chloramphenicol-, and rifampicin-resistant bacteria were studied to explore risks associated with selection and regrowth of antibiotic-resistant bacteria after PAA disinfection. The results showed that after exposure to 20 mg/L PAA for 10 min, inactivation of ampicillin-resistant bacteria reached 2.3 log, which was significantly higher than that of total heterotrophic bacteria with a decrease of 2.0-log. In contrast, inactivation of tetracycline- resistant bacteria was significantly less efficient, reaching only 1.1-log. Chloramphenicol and tetracycline-resistant bacteria, as well as total heterotrophic bacteria regrew more than 10 fold compared to those in the untreated wastewater sample with 22 h stilling culture after exposure to 2 or 5 mg/L PAA as for 10 min. Selection and potential regrowth of tetracycline-and chloramphenicol-resistant bacteria are potential risks when utilizing PAA disinfection, which may induce the spread of specific antibiotic-resistant bacteria in reclaimed water. PMID- 24215885 TI - National data of Class A, B, and C communicable diseases in September 2013 in China. PMID- 24215884 TI - Hypobaric-hypoxia induces alteration in microbes and microbes-associated enzyme profile in rat colonic samples. AB - Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures (70 kPa and 40 kPa) for different time durations (1, 3, and 5 h) and the bacterial community composition was compared with normobaric groups (101.3 kPa). It was found that the total anaerobes, Escherichia coli, Enterbacters spp., Bifidobacterium spp., Clostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, beta-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microflora-derived functional aspects. PMID- 24215887 TI - Parasite infection drives the evolution of state-dependent dispersal of the host. AB - Dispersal plays a fundamental role in shaping the ecological processes such as host-parasite interactions, and the understanding of host dispersal tendency leads to that of parasites. Here, we present the result of our study on how the evolutionarily stable dispersal of a host would depend on parasite infection, considering kin competition among neighbours. We show that the evolving dispersal rate might be higher for susceptible than for infected individuals (S-biased dispersal) or vice versa (I-biased dispersal). S-biased dispersal is favoured by strong virulence affecting competitive ability, by high rate of parasite release during dispersal, and by low virulence for infected emigrants (i.e. low virulence affecting dispersal ability), whereas I-biased dispersal is favoured in the opposite situation. We also discuss population structure or between-deme genetic differentiation of the host measured with Wright's FST. In I-biased dispersal, between-deme genetic differentiation decreases with the infection rate, while in S-biased dispersal, genetic differentiation increases with infection rate. PMID- 24215888 TI - Comparative study of Se oxyanions retention on three argillaceous rocks: Upper Toarcian (Tournemire, France), Black Shales (Tournemire, France) and Opalinus Clay (Mont Terri, Switzerland). AB - A comparative study of selenium oxyanion sorption was carried out by means of batch sorption experiments on three argillaceous rocks that differ in their mineralogical compositions and textural properties. The results show no selenate (Se(VI)) sorption onto the argillaceous rocks after 60 days, but clear sorption of selenite (Se(IV)), the extent being closely related to the initial Se(IV) concentration. At the lowest concentration ([Se(IV)]eq < 10(-8) mol L(-1)), the ranking of rock affinity for Se(IV) is Black Shales > Opalinus Clay (OPA) > Upper Toarcian, with Rd values of 910 +/- 70, 600 +/- 65 and 470 +/- 70 mL g(-1) respectively. The Se(IV) sorption isotherms acquired for the three argillaceous rocks can be reproduced well by means of Langmuir formalism, particularly with a two-site Langmuir model. The comparison of the Se(IV) sorption isotherms obtained for these three rocks led to identification of pyrite associated with natural organic matter (NOM) as one of the main phases involved in selenium retention. While the desorption results suggested a significant Se(IV) reduction in the Upper Toarcian samples, the reversible sorption shown on the Black Shales and OPA samples was correlated with a sulfate increase, symptomatic of surface oxidation of pyrite which could limit the Se(IV) reduction in favor of sorption. PMID- 24215889 TI - Metabolism-guided discovery of a potent and orally bioavailable urea-based calcimimetic for the treatment of secondary hyperparathyroidism. AB - A series of urea based calcimimetics was optimized for potency and oral bioavailability. Crucial to this process was overcoming the poor pharmacokinetic properties of lead thiazole 1. Metabolism-guided modifications, characterized by the use of metabolite identification (ID) and measurement of time dependent inhibition (TDI) of CYP3A4, were essential to finding a compound suitable for oral dosing. Calcimimetic 18 exhibited excellent in vivo potency in a 5/6 nephrectomized rat model and cross-species pharmacokinetics. PMID- 24215890 TI - Synthesis and biological evaluation of nimesulide based new class of triazole derivatives as potential PDE4B inhibitors against cancer cells. AB - A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via the reaction of aryl amine (obtained from nimesulide) with alpha-chloroacetyl chloride followed by displacing the alpha-chloro group by an azide. Some of the synthesized compounds showed encouraging PDE4B inhibitory properties in vitro that is >50% inhibition at 30 MUM that were supported by the docking studies of these compounds at the active site of PDE4B enzyme (dock scores ~ -28.6 for a representative compound). Two of these PDE4 inhibitors showed promising cytotoxic properties against HCT-15 human colon cancer cells in vitro with IC50 ~ 21-22 MUg/mL. PMID- 24215891 TI - Function-regulating pharmacophores in a sulfonamide class of glucocorticoid receptor agonists. AB - A class of alpha-methyltryptamine sulfonamide glucocorticoid receptor (GR) modulators was optimized for agonist activity. The design of ligands was aided by molecular modeling, and key function-regulating pharmacophoric points were identified that are critical in achieving the desired agonist effect in cell based assays. Compound 27 was profiled in vitro and in vivo in models of inflammation. Analogs could be rapidly prepared in a parallel approach from aziridine building blocks. PMID- 24215892 TI - Discovery of 2,5-diarylnicotinamides as selective orexin-2 receptor antagonists (2-SORAs). AB - The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats. PMID- 24215893 TI - Synthesis and characterization of polyacids from palm acid oil and sunflower oil via addition reaction. AB - In this study aliphatic polyacids were synthesized using palm acid oil (PAO) and sunflower oil (SFO) via addition reaction technique. The synthesized materials were characterized using Fourier-transform infra-red (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) and thermo gravimetric analysis (TGA). Mixing formic acid and hydrogen peroxide with PAO or SFO at the ratio 3:10:1 produced the lowest iodine value of 10.57 and 9.24 respectively, indicating the increase in epoxidization of both oils. Adding adipic acid to the epoxidized oils at a ratio of 1:10 increases the acid values of SFO and PAO to 11.22 and 6.73 respectively. The existence of multi-acid groups present in synthesized polyacid was confirmed by MALD-ToF-MS. This feature indicates a possible value to the biomaterials development. PMID- 24215894 TI - p21-Activated kinase 5: a pleiotropic kinase. AB - The PAKs (p21-activated kinases) are highly conserved serine/threonine protein kinases which comprise six mammalian PAKs. PAK5 (p21-activated kinase 5) is the least understood member of PAKs that regulate many intracellular processes when they are stimulated by activated forms of the small GTPases Cdc42 and Rac. PAK5 takes an important part in multiple signal pathways in mammalian cells and controls a variety of cellular functions including cytoskeleton organization, cell motility and apoptosis. The main goal of this review is to describe the structure, mechanisms underlying its activity regulation, its role in apoptosis and the likely directions of further research. PMID- 24215895 TI - Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution. AB - BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1*10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9*10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts. PMID- 24215896 TI - Cognitive dysfunction in unipolar depression: implications for treatment. AB - OBJECTIVE: The primary objective of this review is to examine the literature assessing abnormalities in neural circuitry and cognition early in the course of major depressive disorder (MDD) and the impact of these features on treatment selection and long-term outcomes. DATA SOURCES: English language and peer reviewed publications were obtained by PubMed/Medline (www.pubmed.org) searches using combinations of major depressive disorder, major depression, or unipolar depression and "first episode", early, cognition, cognitive, executive function and memory. The terms bipolar and psychosis were excluded from the searches. These searches yielded 409 records. STUDY SELECTION: A total of 12 studies, systematic reviews and meta-analyses were selected that evaluated learning, memory and executive function in individuals with major depressive disorder. Additional publications meeting these criteria were identified from the bibliographies of the 12 selected articles and from the "related citations" section of PubMed. RESULTS: Difficulty in concentrating and indecisiveness are reported as among the most troubling symptoms by patients with MDD and may limit functional recovery. Cognitive deficits in memory and decision-making are present early in the course of MDD and may be accompanied by structural abnormalities in the hippocampus and prefrontal cortex involved in cognitive functions. Although resolution of cognitive symptoms of depression lags behind recovery from mood symptoms in many patients, preliminary evidence suggests they may improve with antidepressant therapy, but can also persist residually. CONCLUSIONS: New strategies that target cognitive symptoms of depression in addition to mood symptoms are needed to improve long-term outcomes, particularly functional recovery. PMID- 24215897 TI - Affective temperaments and antidepressant response in the clinical management of mood disorders. AB - BACKGROUND: The aim of this study was to investigate the presence of a relationship between affective temperament and antidepressant treatment response in mood disorder patients. METHODS: The lifetime history of antidepressant response of 90 bipolar disorder patients and 88 major depressive disorder patients were retrospectively evaluated and then assigned to one of four subgroups: complete response (CR), partial response (PR), no response (NR), and antidepressant associated mania response (AAMR). Using TEMPS-Rio de Janeiro - the brief Brazilian version of TEMPS-A - we compared affective temperament subscale scores across these groups. RESULTS: We observed a statistically significant relationship between depressive and anxious affective temperaments and no antidepressant response. In bipolar disorder patients, cyclothymic temperament (p<0.01) and hyperthymic temperament (p<0.05) were associated with antidepressant associated mania. Hyperthymic temperament was associated with complete antidepressant responses in major depressive disorder patients. LIMITATIONS: The evaluation of antidepressant response was retrospective. CONCLUSIONS: Our data are consistent with the theory that affective temperament traits are factors that can influence the antidepressant response and the recovery from depressive episodes, but more longitudinal studies are needed to confirm this theory and our findings. PMID- 24215898 TI - An examination of resilience cross-culturally in child and adolescent survivors of the 2008 China earthquake using the Connor-Davidson Resilience Scale (CD RISC). AB - BACKGROUND: The 2008 Sichuan earthquake in China destroyed towns and village, displaced over a million people and caused thousands of deaths. There is a need to understand how children and adolescents are able to bounce back after this distressing event. This study conducts a psychometric assessment of the Connor Davidson Resilience Scale (CD-RISC) and the measure's validity among children and adolescent survivors in order to identify the factors associated with resilience in this socio-cultural setting. METHODS: Translated and culturally verified versions of the CD-RISC, UCLA-PTSD Index and Birleson Self-rating Depression Scale were used to collect data from 2132 children and adolescents located in post-disaster areas 1 year after the event. RESULTS: Through exploratory factor analysis, a 2-factor model was found and defined by Chinese scholars as Rational Thinking and Self-Awareness. Internal consistency of total CD-RISC was 0.86, 0.91 for Rational Thinking and 0.74 for Self-Awareness. Convergent validity between items ranged from 0.17-0.69 and 0.12-0.20 to the total score. Items related to post-traumatic stress disorder loaded separately than CD-RISC items, demonstrating discriminant validity. CONCLUSIONS: Our findings demonstrate that resilience may be understood and manifested dissimilarly in different socio cultural settings. This study confirms the applicability of the CD-RISC scale to Chinese children and adolescent earthquake survivors, and adds to the richness of resilience research cross-culturally. PMID- 24215900 TI - Hypokalemia mimicking a herniated vertebral disc. AB - BACKGROUND CONTEXT: A herniated vertebral disc is a common cause of paralysis. Other causes include infections, tumors, and neurologic diseases. A rare and dangerous but in most cases easily treatable cause is hypokalemia. Clinically, the acute symptoms may resemble a herniated vertebral disc, but hypokalemia per se is life-threatening by causing heart arrest through ventricular tachycardia or fibrillation. PURPOSE: A patient with back pain and neurologic deficit in the lower extremities after a history of a herniated vertebral disc presented, who finally receives the diagnosis of hypokalemia. STUDY DESIGN: Case report. METHODS: A 25-year-old female patient presenting after a fall with muscle weakness in both legs was followed clinically and radiographically. RESULTS: Neurological examination showed a lower extremity muscle weakness with three fifths muscular strength of the quadriceps and tibialis anterior muscle on both sides. Reflexes were diminished bilaterally, anal sphincter tone was normal. Plain radiography suggested a posterior rim fracture of L5, but computed tomography did not confirm this diagnosis. The laboratory investigation revealed a hypokalemia of 1.7 mEq/L. On electrolyte replacement, the patient recovered immediately. CONCLUSION: This report describes a misleading diagnostic case of back pain and neurologic deficit after a trauma and sensitizes for the possible life-threatening diagnosis hypokalemia, which is rare but easily treatable. PMID- 24215899 TI - Perinatal factors and the risk of bipolar disorder in Finland. AB - BACKGROUND: Complications during the perinatal period have been associated with neurodevelopmental disorders like schizophrenia and autism. However, similar studies on bipolar disorder (BPD) have been limited and the findings are inconsistent. The aim of this study was to examine the association between perinatal risk factors and BPD. METHODS: This nested case-control study, based on the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), identified 724 cases and 1419 matched controls from population based registers. Conditional logistic regression was used to examine the associations between perinatal factors and BPD adjusting for potential confounding due to maternal age, psychiatric history and educational level, place of birth, number of previous births and maternal smoking during pregnancy. RESULTS: Children delivered by planned cesarean section had a 2.5-fold increased risk of BPD (95% CI: 1.32-4.78, P<0.01). No association was seen between other examined perinatal risk factors and BPD. LIMITATIONS: The limitations of this study include: the restriction in the sample to treated cases of BPD in the population, and usage of hospital based clinical diagnosis for case ascertainment. In addition, in spite of the large sample size, there was low power to detect associations for certain exposures including the lowest birth weight category and pre-term birth. CONCLUSIONS: Birth by planned cesarean section was associated with risk of BPD, but most other perinatal risk factors examined in this study were not associated with BPD. Larger studies with greater statistical power to detect less common exposures and studies utilizing prospective biomarker-based exposures are necessary in the future. PMID- 24215901 TI - The effect of neighboring segments on the measurement of segmental stiffness in the intact lumbar spine. AB - BACKGROUND CONTEXT: Degeneration, injury, and surgical interventions may alter the mechanical properties of spinal motion segments, but the quantification of these alterations in vivo is problematic. Manual or instrumented loading of single segments in the intact spine as applied intraoperatively may overestimate the mechanical properties of this segment, because the applied load is partly sustained by the adjacent segments. PURPOSE: The distribution of stiffness values of individual spinal segments within and across spines was determined so as to use these data as input to a model simulation of segment stiffness tests in intact spines, to assess measurement errors. STUDY DESIGN: Biomechanical stiffness measurements on human cadaveric spines and model simulation to assess measurement errors. METHODS: Seventeen human cadaveric lumbar spines were loaded with pure moments in flexion/extension, lateral bending, and torsion. An optical system was used to measure the angular rotations of each motion segment and load displacement curves were used to determine stiffness. With the distribution of measured stiffness data as input, a stochastic mechanical model was constructed to investigate how the stiffness of adjacent segments influences stiffness estimates obtained by loading a single segment in the intact spine. RESULTS: The variance in stiffness values was high for all directions, but covaried between segments within a spine. Model simulations indicated that stiffness estimates obtained by loading a single segment in an intact spine are highly correlated with actual stiffness, but overestimate stiffness by a median of 18% with peak errors of close to 400%. CONCLUSION: Current measurement devices and manual assessment substantially overestimate segmental stiffness due to the effect of adjacent spinal levels. In addition, the variance in stiffness within spines can occasionally cause large errors, which might lead to erroneous surgical decisions. PMID- 24215902 TI - Lessons learnt from the development of the Patient Safety Incidents Reporting an Learning System for the Spanish National Health System: SiNASP. AB - OBJECTIVE: To describe the development process and characteristics of a patient safety incidents reporting system to be implemented in the Spanish National Health System, based on the context and the needs of the different stakeholders. DESIGN: Literature review and analysis of most relevant reporting systems, identification of more than 100 stakeholder's (patients, professionals, regional governments representatives) expectations and requirements, analysis of the legal context, consensus of taxonomy, development of the software and pilot test. RESULTS: Patient Safety Events Reporting and Learning system (Sistema de Notificacion y Aprendizajepara la Seguridad del Paciente, SiNASP) is a generic reporting system for all types of incidents related to patient safety, voluntary, confidential, non punitive, anonymous or nominative with anonimization, system oriented, with local analysis of cases and based on the WHO International Classification for Patient Safety. The electronic program has an on-line form for reporting, a software to manage the incidents and improvement plans, and a scoreboard with process indicators to monitor the system. CONCLUSIONS: The reporting system has been designed to respond to the needs and expectations identified by the stakeholders, taking into account the lessons learned from the previous notification systems, the characteristics of the National Health System and the existing legal context. The development process presented and the characteristics of the system provide a comprehensive framework that can be used for future deployments of similar patient safety systems. PMID- 24215903 TI - Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers. AB - BACKGROUND: Long-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers. METHODS: Consecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed. RESULTS: Of 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 - 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 - 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3 methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development. CONCLUSION: The use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers. PMID- 24215904 TI - Low-dose computed tomography of the lumbar spine: a phantom study on imaging parameters and image quality. AB - BACKGROUND: Lumbar spine radiography has limited diagnostic value but low radiation dose compared with computed tomography (CT). The average effective radiation dose from lumbar spine radiography is about 1.1 mSv. Low-dose lumbar spine CT may be an alternative to increase the diagnostic value at low radiation dose, around 1 mSv. PURPOSE: To determine the optimal settings for low-dose lumbar spine CT simultaneously aiming for the highest diagnostic image quality possible. MATERIAL AND METHODS: An ovine lower thoracic and lumbar spine phantom, with all soft tissues around the vertebrae preserved except the skin, was placed in a 20 L plastic container filled with water. The phantom was scanned repeatedly with various technical settings; different tube potential, reference mAs, and with different convolution filters. Five radiologists evaluated the image quality according to a modification of the European guidelines for multislice computed tomography (MSCT) quality criteria for lumbar spine CT 2004. In a visual comparison the different scans were also ranked subjectively according to perceived image quality. Image noise and contrast were measured. RESULTS: A tube potential of 120 kV with reference mAs 30 and medium or medium smooth convolution filter gave the best image quality at a sub-millisievert dose level, i.e. with an effective dose comparable to that from lumbar spine radiography. CONCLUSION: Low dose lumbar spine CT thus opens a possibility to substitute lumbar spine radiography with CT without obvious increase in radiation dose. PMID- 24215905 TI - Usefulness of monochromatic imaging with metal artifact reduction software for computed tomography angiography after intracranial aneurysm coil embolization. AB - BACKGROUND: Recently, a newly developed fast-kV switching dual energy CT scanner with a gemstone detector generates virtual high keV images as monochromatic imaging (MI). Each MI can be reconstructed by metal artifact reduction software (MARS) to reduce metal artifact. PURPOSE: To evaluate the degree of metal artifacts reduction and vessel visualization around the platinum coils using dual energy CT with MARS. MATERIAL AND METHODS: Dual energy CT was performed using a Discovery CT750 HD scanner (GE Healthcare, Milwaukee, WI, USA). In a phantom study, we measured the mean standard deviation within regions of interest around a 10-mm-diameter platinum coil mass on MI with and without MARS. Thirteen patients who underwent CTA after endovascular embolization for cerebral aneurysm with platinum coils were included in a clinical study. We visually assessed the arteries around the platinum coil mass on MI with and without MARS. RESULTS: Each standard deviation near the coil mass on MI with MARS was significantly lower than that without MARS in a phantom study. On CTA of a clinical study, better visibility of neighboring arteries was obtained in 11 of 13 patients on MI with MARS compared to without MARS due to metal artifact reduction. CONCLUSION: Dual energy CT with MARS reduces metal artifact of platinum coils, resulting in favorable vessel visualization around the coil mass on CTA after embolization. PMID- 24215906 TI - Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children. AB - BACKGROUND: Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. METHODS: Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P <= 0.05. RESULTS: The mean age of patients in the HR group was 1.4 +/- 0.9 y and in the LR group 2.8 +/ 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. CONCLUSIONS: Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated. PMID- 24215907 TI - Molecular and immunological characterization of beta'-component (Onc k 5), a major IgE-binding protein in chum salmon roe. AB - Salmon roe has a high allergic potency and often causes anaphylaxis in Japan. The major allergic protein of salmon roe is beta'-component, which is a 35kDa vitellogenin fragment consisting of two subunits. To elucidate structural information and immunological characteristics, beta'-component and the subunit components were purified from chum salmon (Onchorhincus keta) roe and vitellogenin-encoding mRNA was used to prepare beta'-component subunit-encoding cDNA. This was PCR-amplified, cloned and sequenced and the deduced amino acid sequence compared with partial sequences of beta'-component obtained by peptide mapping. The recombinant beta'-component subunit was produced by bacterial expression in Escherichia coli and its IgE-binding ability was measured by ELISA using the sera of a patient allergic to salmon roe. This was then compared with that of the native beta'-component with and without carboxymethylation. Following successful cloning of the cDNA encoding the beta'-component subunit, 170 amino acid residues were deduced and matched with the amino acid sequences of 121 and 88 residues in the 16kDa and 18kDa subunits, respectively. The sequences of both beta'-component subunits were almost identical, and the predicted secondary structure of the beta'-component showed a high content of beta-pleated sheets and no alpha-helices. There was no difference in IgE-binding ability between the native and recombinant beta'-component subunits at the same protein concentration, regardless of carboxymethylation. In conclusion, beta'-component is a homodimer protein composed of two isoform subunits having the same level of IgE-binding ability and, therefore, allergenic identity. PMID- 24215908 TI - Preparation of stabilized magnetic nanoparticles with polymerizable lipid and anchor compounds. AB - Although the lipid-based method for coating of magnetic nanoparticles (MNPs) is rapid and simple, the unstable state of the lipid layer is a major limitation for the practical application of this method. We devised a method to prepare stabilized MNPs by covalent modifications such as lipid polymerization and anchoring of the lipid layer. The stability of the modified lipid layer was demonstrated by the stable status of enzymes immobilized on the MNPs and the resistance of the MNPs to aggregation. We also determined the maximum ratio of nonpolymerizable lipophilic compounds that can be included in the layer without significantly reducing stability. PMID- 24215909 TI - Microsphere-based immunoassay for the detection of azaspiracids. AB - Azaspiracids (AZAs) are a group of lipophilic toxins discovered in mussels from Ireland in 1995 following a human poisoning incident. Nowadays the regulatory limit for AZAs in many countries is set at 160 MUg of azaspiracid equivalents per kilogram of shellfish meat. In this work a microsphere-based immunoassay has been developed for the detection of AZAs using a Luminex system. This method is based on the competition between AZA-2 immobilized onto the surface of microspheres and free AZAs for the interaction with a monoclonal anti-azaspiracid antibody (mAb 8F4). In this inhibition immunoassay the amount of mAb 8F4 bound to AZA-2 microspheres was quantified using a phycoerythrin-labeled anti-mouse antibody, and the fluorescence was measured with a Luminex analyzer. Simple acetate/methanol or methanol extractions yielded final extracts with no matrix interferences and adequate recovery rates of 86.5 and 75.8%, respectively. In summary, this work presents a sensitive and easily performed screening method capable of detecting AZAs at concentrations below the range of the European regulatory limit using a microsphere/flow cytometry system. PMID- 24215911 TI - The impacts of handling and air exposure on immune parameters, gene expression, and susceptibility to vibriosis of European abalone Haliotis tuberculata. AB - Wild or farmed abalone are regularly exposed to stressors, such as air exposure and handling. Immune and transcriptional responses as well as susceptibility to vibriosis of sexually mature or immature European abalone acclimated at 16 or 19 degrees C were determined following handling or air exposure. Hemocyte density and H2O2 production increased while hemocyte viability and phagocytic index decreased following handling. Air exposure induces a decrease of hemocyte density and phagocytic index. Measurement of the expression of genes implicated in general metabolic, immunological and stress responses in gills, foot-muscle and hemocytes by real time q-PCR suggested that both stressors lead to a metabolic rate depression, characterized by a general inhibition of transcription. Finally, following handling a Vibrio harveyi challenge enhances almost 100% mortality of sexually immature animals at 19 degrees C while it has been previously demonstrated that only mature are susceptible to vibriosis. PMID- 24215910 TI - Weak protein-protein interactions revealed by immiscible filtration assisted by surface tension. AB - Biological mechanisms are often mediated by transient interactions between multiple proteins. The isolation of intact protein complexes is essential to understanding biochemical processes and an important prerequisite for identifying new drug targets and biomarkers. However, low-affinity interactions are often difficult to detect. Here, we use a newly described method called immiscible filtration assisted by surface tension (IFAST) to isolate proteins under defined binding conditions. This method, which gives a near-instantaneous isolation, enables significantly higher recovery of transient complexes compared to current wash-based protocols, which require reequilibration at each of several wash steps, resulting in protein loss. The method moves proteins, or protein complexes, captured on a solid phase through one or more immiscible-phase barriers that efficiently exclude the passage of nonspecific material in a single operation. We use a previously described polyol-responsive monoclonal antibody to investigate the potential of this new method to study protein binding. In addition, difficult-to-isolate complexes involving the biologically and clinically important Wnt signaling pathway were isolated. We anticipate that this simple, rapid method to isolate intact, transient complexes will enable the discoveries of new signaling pathways, biomarkers, and drug targets. PMID- 24215912 TI - Determination of sialic acids in immune system cells (coelomocytes) of sea urchin, Paracentrotus lividus, using capillary LC-ESI-MS/MS. AB - Coelomocytes are considered to be immune effectors of sea urchins. Coelomocytes are the freely circulating cells in the body fluid contained in echinoderm coelom and mediate the cellular defence responses to immune challenges by phagocytosis, encapsulation, cytotoxicity and the production of antimicrobial agents. Coelomocytes have the ability to recognize self from non-self. Considering that sialic acids play important roles in immunity, we determined the presence of sialic acid types in coelomocytes of Paracentrotus lividus. Homogenized coelomocytes were kept in 2 M aqueous acetic acid at 80 degrees C for 3 h to liberate sialic acids. Sialic acids were determined by derivatization with 1,2 diamino-4,5-methylenediaoxy-benzene dihydrochloride (DMB) followed by capillary liquid-chromatography-electrospray ionization/tandem mass spectrometry (CapLC-ESI MS/MS). Standard sialic acids; Neu5Ac, Neu5Gc, KDN and bovine submaxillary mucin showing a variety of sialic acids were used to confirm sialic acids types. We found ten different types of sialic acids (Neu5Gc, Neu5Ac, Neu5Gc9Ac, Neu5Gc8Ac, Neu5,9Ac2, Neu5,7Ac2, Neu5,8Ac2, Neu5,7,9Ac3, Neu5Gc7,9Ac2, Neu5Gc7Ac) isolated in limited amounts from total coelomocyte population. Neu5Gc type of sialic acids in coelomocytes was the most abundant type sialic acid when compared with other types. This is the first report on the presence of sialic acid types in coelomocytes of P. lividus using CapLC-ESI-MS/MS-Ion Trap system (Capillary Liquid Chromatography-Electrospray Ionization/Tandem Mass Spectrometry). PMID- 24215915 TI - History of acupuncture research. AB - The acupuncture has been practiced in China for more than 3000 years and was spread to Europe and American from the sixteenth to the nineteenth century. The history of acupuncture research was initiated in the eighteenth century and developed rapidly since then. In the past, physicians tried hard to apply acupuncture into clinical practice, while scientists were focused on the possible characteristics of acupoints and meridians. In the modern time, scientists have strived hard to evaluate the real effectiveness of acupuncture and the underlying physiological and biological mechanisms of acupuncture. Reviewing research history from past to present, we are delighted to witness this wonderful development. Accumulated evidences that acupuncture is beneficial in various conditions significantly enhanced our understanding the mechanisms of acupuncture treatment. However, there is still no conclusive evidence in acupuncture clinical studies. The clinical research still needs great improving, while the basic research results need to be appropriately transformed into clinical outcomes. Based on current achievements, we believe that although the challenges and difficulties exist, a more collaborative, innovative, and integrated approach will help us to achieve further progress in future acupuncture research. PMID- 24215914 TI - The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation. AB - The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti inflammatory effect of T3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor beta1 as the major player mediating T3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems. PMID- 24215913 TI - HCV infection selectively impairs type I but not type III IFN signaling. AB - A stable and persistent Hepatitis C virus (HCV) replication cell culture model was developed to examine clearance of viral replication during long-term treatment using interferon-alpha (IFN-alpha), IFN-lambda, and ribavirin (RBV). Persistently HCV-infected cell culture exhibited an impaired antiviral response to IFN-alpha+RBV combination treatment, whereas IFN-lambda treatment produced a strong and sustained antiviral response that cleared HCV replication. HCV replication in persistently infected cells induced chronic endoplasmic reticulum (ER) stress and an autophagy response that selectively down-regulated the functional IFN-alpha receptor-1 chain of type I, but not type II (IFN-gamma) or type III (IFN-lambda) IFN receptors. Down-regulation of IFN-alpha receptor-1 resulted in defective JAK-STAT signaling, impaired STAT phosphorylation, and impaired nuclear translocation of STAT. Furthermore, HCV replication impaired RBV uptake, because of reduced expression of the nucleoside transporters ENT1 and CNT1. Silencing ER stress and the autophagy response using chemical inhibitors or siRNA additively inhibited HCV replication and induced viral clearance by the IFN alpha+RBV combination treatment. These results indicate that HCV induces ER stress and that the autophagy response selectively impairs type I (but not type III) IFN signaling, which explains why IFN-lambda (but not IFN-alpha) produced a sustained antiviral response against HCV. The results also indicate that inhibition of ER stress and of the autophagy response overcomes IFN-alpha+RBV resistance mechanisms associated with HCV infection. PMID- 24215916 TI - Effects of acupuncture needling with specific sensation on cerebral hemodynamics and autonomic nervous activity in humans. AB - Effective therapeutic factors in acupuncture therapy include specific stimulation points, called acupoints, and specific sensations, called de-qi, that are induced by needling manipulation. Human neuroimaging studies have reported that acupuncture stimulation with de-qi sensations induced specific activity patterns in the brain and modulated autonomic nervous activity. However, acupoints and nonacupoints have been reported to induce de-qi sensations. Thus, it remains unclear whether these physiological responses induced by acupuncture and associated with therapeutic efficacy are related to specific stimulation sites (acupoints) or unique de-qi sensations. This review focuses on the cerebral hemodynamic responses and autonomic nervous activity changes induced by acupuncture stimulation at acupoints and nonacupoints with and without de-qi sensations. We argue that the specific sensations induced by acupuncture are more important than the specific stimulation sites for inducing cerebral hemodynamic and autonomic responses and that autonomic responses during acupuncture, which might be important for therapeutic efficacy, might be mediated though the brain activity changes exemplified by the cerebral hemodynamic responses during acupuncture. PMID- 24215917 TI - Acupuncture point specificity. AB - Acupuncture, as a modality treatment, has gained increasing popularity and acceptance between public and health-care professionals worldwide. Recently, there has been intensive debate about the efficacy of acupuncture therapy due to the conflicting outcome of clinical trials. Acupoint specificity was regarded as one of the core scientific issues with respect to acupuncture practice at the Society for Acupuncture Research international symposium held in 2007. In this chapter, we reviewed the recent development in basic science and clinical studies on the role of acupoint specificity. The evidence cumulated from brain imaging and many biological studies showed that the point specificity in acupuncture does exist, although acupoint specificity-related issues such as sham acupoint and placebo phenomenon need to be seriously considered. How to optimize the efficacy of acupoint and minimize the impact of sham acupuncture is an urgent issue faced by acupuncture community, and more studies are warranted on the subjects. PMID- 24215918 TI - Acupuncture stimulation induces neurogenesis in adult brain. AB - The discovery of adult neurogenesis was a turning point in the field of neuroscience. Adult neurogenesis offers an enormous possibility to open a new therapeutic paradigm of neurodegenerative diseases and stroke. Recently, several studies suggested that acupuncture may enhance adult neurogenesis. Acupuncture has long been an important treatment for brain diseases in the East Asia. The scientific mechanisms of acupuncture treatment for the diseases, such as Alzheimer's disease, Parkinson's disease, and stroke, have not been clarified yet; however, the neurogenic effect of acupuncture can be a possible reason. Here, we have reviewed the studies on the effect of stimulation at various acupoints for neurogenesis, such as ST36 and GV20. The suggested mechanisms are also discussed including upregulation of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor and neuropeptide Y, and activation of the function of primo vascular system. PMID- 24215919 TI - Acupuncture and neurotrophin modulation. AB - The Western explanation for acupuncture effectiveness is based upon more than half a century of basic and clinical research, which identified the activation of sensory system and the subsequent activity-dependent regulation of neurotransmitters, neurohormones, and several classes of neuromodulators as plausible mechanism for the acupuncture's therapeutic properties. The regulation of neurotrophins' expression and activity is one of the possible neurophysiological mechanisms underlying acupuncture's effects on neuropathic pain, nerve injury, neurodegeneration, and even in the regulation of gonadal functions. The present work will review the scientific literature produced by a decade of investigations on the relationship between acupuncture and neurotrophins. This scientific production and the current knowledge about the neural and neurohormonal activity-dependent regulation of neurotrophin expression/action suggest the existence of a link between the ability of acupuncture in regulating neural physiology and its effects on the neurotrophic milieu in different disease states. PMID- 24215920 TI - Acupuncture stimulation and neuroendocrine regulation. AB - Acupuncture has been used to treat different conditions for at least 3000 years in China and has gained increasing acceptance worldwide. The acupuncture needle inserted into the muscle layer at the acupoint produces the so-called obtaining qi sensation that causes the excitation of A-delta and C-fibers of the muscle tissue, resulting in afferent signals. The afferent signals pass through the dorsal horn cells of the spinal cord ascending to the brain, such as the hypothalamus, enhancing the release of neuropeptides and hormones, and these afferent signals in the spinal segment may innervate the visceral organ, inducing effect on visceral function. Here, we reviewed the effect of acupuncture stimulation on neuropeptides and hormones, including beta-endorphin, serotonin, oxytocin, adrenocorticotropic hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, cholecystokinin, and acetylcholine, as well as insulin sensitivity, immunomodulation (anti-inflammation), and autonomic nerve activity. PMID- 24215921 TI - Current development of acupuncture research in Parkinson's disease. AB - Parkinson's disease is an age-related progressive neurodegenerative disease. The etiology and pathogenetic mechanisms that cause PD are still not fully understood. The available treatments to PD are only symptomatic relief. Acupuncture is used to treat many medical conditions for 1000 years in China and has gained wider and increasing acceptance within both public and medical profession because it has been a very safe and well-tolerated treatment. In this chapter, we reviewed relevant laboratory findings regarding acupuncture mechanism on Parkinson's. We showed that acupuncture stimulation in Parkinson's models had generated valuable mechanistic insight of Parkinson's and showed that acupuncture treatment is in fact a neuroprotective therapy that increase the release of various neuroprotective agents such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and cyclophilin A. In addition, acupuncture therapy slows cell death process and attenuates oxidative stress to dopaminergic neurons in the substantia nigra. Further, acupuncture therapy modulates neuronal activity of the basal ganglia output structures. These results suggest that early application of acupuncture therapy to Parkinson's patients may be helpful for the best efficacy of acupuncture treatment. It is hopeful that translation of achievement in acupuncture research in Parkinson's models will maximize the potentials of acupuncture treatment. PMID- 24215922 TI - Acupuncture therapy for stroke patients. AB - Acupuncture is one of the most important parts of Traditional Chinese Medicine, has been used for more than 3000 years as prevention and treatment for various diseases in China as well as in adjacent regions, and is widely accepted in western countries in recent years. More and more clinical trials revealed that acupuncture shows positive effect in stroke, not only as a complementary and alternative medicine for poststroke rehabilitation but also as a preventive strategy which could induce cerebral ischemic tolerance, especially when combined with modern electrotherapy. Acupuncture has some unique characteristics, which include acupoint specificity and parameter-dependent effect. It also involves complicated mechanism to exert the beneficial effect on stroke. Series of clinical trials have shown that acupuncture primarily regulates the release of neurochemicals, hemorheology, cerebral microcirculation, metabolism, neuronal activity, and the function of specific brain region. Animal studies showed that the effects of acupuncture therapy on stroke were possibly via inhibition of postischemic inflammatory reaction, stimulation of neurogenesis and angiogenesis, and influence on neural plasticity. Mechanisms for its preconditioning effect include activity enhancement of antioxidant, regulation of the endocannabinoid system, and inhibition of apoptosis. Although being controversial, acupuncture is a promising preventive and treatment strategy for stroke, but further high quality clinical trials would be needed to provide more confirmative evidence. PMID- 24215923 TI - Effect and mechanism of acupuncture on Alzheimer's disease. AB - Alzheimer's disease is the most common form of dementia diagnosed in the aging population worldwide. The cause of Alzheimer's is still not clear. There is no cure for the disease and current treatments are only symptomatic relieve. The search for new treatment is made ever more urgent due to increasing population aging. Acupuncture has been in practice in China for more than 3000 years and used to treat a wide variety of conditions including cardiovascular and psychiatric diseases, acute, and chronic pain. In this chapter, we review recent development on the effects and mechanisms of acupuncture on Alzheimer's disease. In Alzheimer's animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Abeta proteins in the hippocampus and relevant brain regions. The biochemical modulations by acupuncture in the brains of Alzheimer's models are correlated with the cognitive improvement. In Alzheimer's patients, functional brain images demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe which are related to the memory and cognitive function. Although only a few acupuncture clinical studies with a small number of participants are reported, they represent an important step forward in the research of both acupuncture and Alzheimer's. Translation of acupuncture research in animal model studies into the human subjects will undoubtedly enhance acupuncture efficacy in clinical study and treatment which could eventually lead to a safer, well tolerated and inexpensive form of care for Alzheimer's patients. PMID- 24215924 TI - Acupuncture therapy for psychiatric illness. AB - Acupuncture has traditionally been used for problems including anxiety, insomnia, stress, and depression in China and other East Asian countries. A range of different neurobiological responses to acupuncture have been investigated including modulation of serotonergic, noradrenergic, and dopaminergic systems; effects on GABA and the hypothalamic-pituitary-adrenal axis; and inflammatory responses. Interpretation of the findings is challenging because the neurobiology of psychiatric disorders has yet to be fully elucidated. Limitations also arise from the use of animal models and the selection of appropriate control treatments. Further complexity is added by acupuncture treatment being nonstandardized with acupuncture points often selected on the basis on traditional practice and theory. Potentially promising findings require further investigation and substantiation. PMID- 24215925 TI - Acupuncture for the treatment of insomnia. AB - Insomnia appears to be a fast-spreading problem in the modern days, which not only affects people's living quality but also impairs people's working efficiency even causing disability. Pharmacological treatment is effective but frequently with significant side effects. Acupuncture is traditionally used for the treatment of insomnia in China and now is widely accepted in the Western countries. Many research works on clinical applications of acupuncture in the treatment of insomnia and the potential mechanisms underlying the acupuncture treatment have been reported. This chapter will try to provide a systematic review on the research findings. A number of clinical studies, mainly randomized controlled clinical trials, have shown positive effects in acupuncture treatment of insomnia. Some of the studies demonstrated that acupuncture treatment appeared to be better than conventional pharmacological drugs in the improvement of insomnia. These encouraging findings are limited by the qualities problems of the methodology used in these clinical studies. The clinical efficacy of acupuncture appeared to be supported by evidence obtained from basic neuroendocrinological studies. A number of studies have demonstrated that acupuncture may modulate a wide range of neuroendocrinological factors following stimulation of acupoints. Evidence has suggested that the clinical efficacy of acupuncture in treatment of insomnia is potentially mediated by a variety of neurotransmitters including norepinephrine, melatonin, gamma-aminobutyric acid, and beta-endorphin. However, due to the complexity, these findings are far from conclusive. More research is necessary. More rigors methodology and integrated approach to evaluate both clinical and basic research evidence are required for future studies. PMID- 24215926 TI - Acupuncture for the treatment of drug addiction. AB - Over the last four decades, there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. Wen of Hong Kong was the first (1972) to report that acupuncture at four body points and two ear points combined with electric stimulation can relieve opioid withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the United States, who finalized a protocol (1985), using only ear points without electric stimulation for the treatment of cocaine dependence. The recent advance in this field was made by Dr. Han of the Peking University, Beijing, who characterized a protocol (2005), using electric stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and reduce relapse of heroin use. In this chapter, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed. PMID- 24215927 TI - Acupuncture regulation of blood pressure: two decades of research. AB - Although mechanisms underlying acupuncture regulation of pain have been studied by a number of laboratories in many countries, much less is known about its ability to modulate cardiovascular function. In the last two decades, our laboratory has systematically investigated the peripheral and central neural mechanisms underlying acupuncture regulation of blood pressure. These observations account for acupuncture's distant actions and, to some extent, its local actions, with respect to the site of needling. Four fundamental findings have advanced our knowledge. First, point-specific effects of acupuncture underlie its cardiovascular actions. Second, variable regions in the supraspinal and spinal central nervous system that receive input from somatic afferent stimulation account for acupuncture's ability to modulate blood pressure. Thus, depending on the underlying situation, for example, high or low blood pressure, acupuncture modifies autonomic outflow by reducing activity in brain stem nuclei that participate in the primary response. Third, repetitive acupuncture through a molecular mechanism can cause prolonged cardiovascular effects that far outlast acupuncture stimulation. Fourth, there is a range of cardiovascular responsiveness to acupuncture that depends, at least in part, on interactions between neural modulators that synaptically regulate autonomic function in the brain stem. Thus, acupuncture has the capability of profoundly regulating cardiovascular function in patients with disease, for example, hypertension, and the experimental laboratory is directing best approaches to study its actions in humans. PMID- 24215928 TI - Effect and mechanism of acupuncture on gastrointestinal diseases. AB - Acupuncture modulates various biomechanical responses, such as prokinetic, antiemetic, and antinociceptive effects. Acupuncture treatment involves the insertion of thin needles into the skin and underlying muscle and the needles are stimulated manually or electrically. Thus, acupuncture stimulates the somatic afferent nerves of the skin and muscles. The somatic sensory information from the body is carried to the cortex area of the brain. Somatic sensory fibers also project to the various nuclei, including the brain stem, periaqueductal gray (PAG), and paraventricular nucleus (PVN) of the hypothalamus. Somatosensory pathways stimulated by acupuncture activate these nuclei. Activation of the brain stem modulates the imbalance between sympathetic activity and parasympathetic activity. Opioid released from the PAG is involved in mediating antiemetic and antinociceptive effects of acupuncture. Oxytocin release from the PVN mediates antistress and antinociceptive effects of acupuncture. Acupuncture may be effective in patients with functional gastrointestinal (GI) disorders because of its effects on GI motility and visceral pain. It is expected that acupuncture is used in the treatment of patients with functional GI disorders. PMID- 24215929 TI - Acupuncture is a fundamental part of traditional Chinese medicine. Preface. PMID- 24215930 TI - Arabidopsis cysteine-rich receptor-like kinase 45 positively regulates disease resistance to Pseudomonas syringae. AB - Arabidopsis cysteine-rich receptor-like protein kinase 45 (CRK45) was found to be involved in ABA signaling in Arabidopsis thaliana previously. Here, we reported that it also positively regulates disease resistance. The CRK45 overexpression plants increased expression of the defense genes, and enhanced resistance to Pseudomonas syringae whereas the crk45 mutant were more sensitive to P. syringae and weakened expression of the defense genes, compared to the wild type. We also found that treatment with P. syringae leads to a declined expression of CRK45 in the npr1 mutant and the NahG transgenic plants. At the same time, significantly decreased expression of CRK45 transcript in the wrky70 mutant than that in the wild type was also detected. Our results suggested that CRK45 acted as a positive regulator in Arabidopsis disease resistance, and was regulated downstream of NPR1 and WRKY70 at the transcriptional level. PMID- 24215931 TI - Genome-wide analysis and expression profiling of the Solanum tuberosum aquaporins. AB - Aquaporins belongs to the major intrinsic proteins involved in the transcellular membrane transport of water and other small solutes. A comprehensive genome-wide search for the homologues of Solanum tuberosum major intrinsic protein (MIP) revealed 41 full-length potato aquaporin genes. All potato aquaporins are grouped into five subfamilies; plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and x-intrinsic proteins (XIPs). Functional predictions based on the aromatic/arginine (ar/R) selectivity filters and Froger's positions showed a remarkable difference in substrate transport specificity among subfamilies. The expression pattern of potato aquaporins, examined by qPCR analysis, showed distinct expression profiles in various organs and tuber developmental stages. Furthermore, qPCR analysis of potato plantlets, subjected to various abiotic stresses revealed the marked effect of stresses on expression levels of aquaporins. Taken together, the expression profiles of aquaporins imply that aquaporins play important roles in plant growth and development, in addition to maintaining water homeostasis in response to environmental stresses. PMID- 24215933 TI - Rapid determination of alendronate to quality evaluation of tablets by high resolution 1H NMR spectroscopy. AB - Determination of alendronate is crucial to routine quality control of alendronate tablets. However, tedious sample treatment processes such as derivatization were generally required by chromatographic separation of alendronate as its high polarity and no chromophore in the molecular structure. Here, we describe the use of (1)H NMR for the quantification of alendronate sodium in tablets. Linearity, recovery, selectivity and sensitivity of the assay were validated to be satisfactory with quick sample preparation and acquisition. The contents of alendronate sodium in tablets from five manufacturers were determined, the results showed that all assayed tablets fell within the range of 90.0-110.0% of the label claim and the relative standard deviation was less than 6.0%. The method was also successfully employed for alendronate tablet dissolution assay in this study. PMID- 24215934 TI - Translation invariant directional framelet transform combined with Gabor filters for image denoising. AB - This paper is devoted to the study of a directional lifting transform for wavelet frames. A nonsubsampled lifting structure is developed to maintain the translation invariance as it is an important property in image denoising. Then, the directionality of the lifting-based tight frame is explicitly discussed, followed by a specific translation invariant directional framelet transform (TIDFT). The TIDFT has two framelets psi1, psi2 with vanishing moments of order two and one respectively, which are able to detect singularities in a given direction set. It provides an efficient and sparse representation for images containing rich textures along with properties of fast implementation and perfect reconstruction. In addition, an adaptive block-wise orientation estimation method based on Gabor filters is presented instead of the conventional minimization of residuals. Furthermore, the TIDFT is utilized to exploit the capability of image denoising, incorporating the MAP estimator for multivariate exponential distribution. Consequently, the TIDFT is able to eliminate the noise effectively while preserving the textures simultaneously. Experimental results show that the TIDFT outperforms some other frame-based denoising methods, such as contourlet and shearlet, and is competitive to the state-of-the-art denoising approaches. PMID- 24215932 TI - Altered subcellular localization of the NeuN/Rbfox3 RNA splicing factor in HIV associated neurocognitive disorders (HAND). AB - The anti-NeuN antibody has been widely used for over 15 years to unambiguously identify post-mitotic neurons in the central nervous system of a wide variety of vertebrates including mice, rats and humans. In contrast to its widely reported nuclear localization, we found significantly higher NeuN reactivity in the cytoplasm of neurons in brain sections from HIV-infected individuals with cognitive impairment compared to controls. The protein target of anti-NeuN antisera was recently identified as the neuron-specific RNA splicing factor, Rbfox3, but its significance in diseases affecting the brain has not been previously reported. RNA splicing occurs in the nucleus hence, the altered localization of RbFox3 to the cytoplasm may lead to the downregulation of neuronal gene expression. PMID- 24215936 TI - Fatigue on the flight deck: the consequences of sleep loss and the benefits of napping. AB - The detrimental effects of fatigue in aviation are well established, as evidenced by both the number of fatigue-related mishaps and numerous studies which have found that most pilots experience a deterioration in cognitive performance as well as increased stress during the course of a flight. Further, due to the nature of the average pilot's work schedule, with frequent changes in duty schedule, early morning starts, and extended duty periods, fatigue may be impossible to avoid. Thus, it is critical that fatigue countermeasures be available which can help to combat the often overwhelming effects of sleep loss or sleep disruption. While stimulants such as caffeine are typically effective at maintaining alertness and performance, such countermeasures do nothing to address the actual source of fatigue - insufficient sleep. Consequently, strategic naps are considered an efficacious means of maintaining performance while also reducing the individual's sleep debt. These types of naps have been advocated for pilots in particular, as opportunities to sleep either in the designated rest facilities or on the flight deck may be beneficial in reducing both the performance and alertness impairments associated with fatigue, as well as the subjective feelings of sleepiness. Evidence suggests that strategic naps can reduce subjective feelings of fatigue and improve performance and alertness. Despite some contraindications to implementing strategic naps while on duty, such as sleep inertia experienced upon awakening, both researchers and pilots agree that the benefits associated with these naps far outweigh the potential risks. This article is a literature review detailing both the health and safety concerns of fatigue among commercial pilots as well as benefits and risks associated with strategic napping to alleviate this fatigue. PMID- 24215935 TI - Modelling binding between CCR5 and CXCR4 receptors and their ligands suggests the surface electrostatic potential of the co-receptor to be a key player in the HIV 1 tropism. AB - BACKGROUND: CCR5 and CXCR4 are the two membrane-standing proteins that, along with CD4, facilitate entry of HIV particles into the host cell. HIV strains differ in their ability to utilize either CCR5 or CXCR4, and this specificity, also known as viral tropism, is largely determined by the sequence of the V3 loop of the viral envelope protein gp120. RESULTS: With statistical and docking approaches we have computationally analyzed binding preferences of CCR5 and CXCR4 to both V3 loop sequences of virus strains of different tropism and endogenous ligands. CONCLUSIONS: We conclude that the tropism cannot be satisfactorily explained by amino-acid interactions alone, and suggest a two-step mechanism, by which initial coreceptor selection and approach of the ligand to the binding pocket is dominated by charge and glycosylation pattern of the viral envelope. PMID- 24215937 TI - Invasive Streptococcus anginosus group infection-does the species predict the outcome? AB - OBJECTIVE: To determine whether there is an association between the species of Streptococcus anginosus group (SAG) bacteria and the clinical outcome. METHODS: Isolates from invasive infections caused by SAG bacteria at our institution between January 2004 and February 2009 were identified phenotypically to the taxonomic level of species. Clinical data from the medical records of the patients from whom these isolates were recovered were obtained retrospectively and analyzed. RESULTS: Patients with invasive Streptococcus intermedius infections had a significantly longer hospital stay than patients infected with S. anginosus (p = 0.024) and a significantly higher 30-day all-cause mortality than patients infected with Streptococcus constellatus (p = 0.049). CONCLUSION: Identification of SAG bacteria to the taxonomic level of species may be of prognostic importance. PMID- 24215938 TI - Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats. AB - Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000ft above the sea level). Iron supplementation (2mg elemental iron/kg, once daily for 15days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25mg/kg, once daily for the last 7days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co administration of antioxidants such as trolox as protective measures. PMID- 24215939 TI - Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study. AB - Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types of urogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence of mutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance of urogenital tumors. PMID- 24215940 TI - A progress report on a prospective randomised trial of open and robotic prostatectomy. AB - A randomised trial of robotic and open prostatectomy commenced in October 2010 and is progressing well. Clinical and quality of life outcomes together with economic costs to individuals and the health service are being examined critically to compare outcomes. PMID- 24215941 TI - Coal-tar-based sealcoated pavement: a major PAH source to urban stream sediments. AB - We used land-use analysis, PAH concentrations and assemblages, and multivariate statistics to identify sediment PAH sources in a small (~1303 km(2)) urbanizing watershed located in South-Central, Pennsylvania, USA. A geographic information system (GIS) was employed to quantify land-use features that may serve as PAH sources. Urban PAH concentrations were three times higher than rural levels, and were significantly and highly correlated with combined residential/commercial/industrial land use. Principal components analysis (PCA) was used to group sediments with similar PAH assemblages, and correlation analysis compared PAH sediment assemblages to common PAH sources. The strongest correlations were observed between rural sediments (n = 7) and coke-oven emissions sources (r = 0.69-0.78, n = 5), and between urban sediments (n = 22) and coal-tar-based sealcoat dust (r = 0.94, n = 47) suggesting that coal-tar based sealcoat is an important urban PAH source in this watershed linked to residential and commercial/industrial land use. PMID- 24215942 TI - Understanding partnership practice in primary health as pedagogic work: what can Vygotsky's theory of learning offer? AB - Primary health policy in Australia has followed international trends in promoting models of care based on partnership between professionals and health service users. This reform agenda has significant practice implications, and has been widely adopted in areas of primary health that involve supporting families with children. Existing research shows that achieving partnership in practice is associated with three specific challenges: uncertainty regarding the role of professional expertise, tension between immediate needs and longer-term capacity development in families, and the need for challenge while maintaining relationships based on trust. Recently, pedagogic or learning-focussed elements of partnership practice have been identified, but there have been no systematic attempts to link theories of learning with the practices and challenges of primary health-care professionals working with families in a pedagogic role. This paper explores key concepts of Vygotsky's theory of learning (including mediation, the zone of proximal development, internalisation, and double stimulation), showing how pedagogic concepts can provide a bridge between the policy rhetoric of partnership and primary health practice. The use of this theory to address the three key challenges is explicitly discussed. PMID- 24215943 TI - Designing interactivity on consumer health websites: PARAFORUM for spinal cord injury. AB - OBJECTIVE: This paper addresses the issue of interactivity on health consumer websites powered by health organizations, by presenting the design of PARAFORUM, an interactive website in the field of spinal cord injury (SCI). METHODS: The design of PARAFORUM is based on different streams of research in online health communication, web-based communities, open innovation communities and formative evaluation with stakeholders. RESULTS: PARAFORUM implements a model of diversified interactivity based on individuals with SCI and their families, health professionals, and researchers sharing their expertise in SCI. In addition to traditional health professional/researcher-to-consumer and peer-to-peer interactions, through PARAFORUM consumers, health professionals and researchers can co-design ideas for the enhancement of practice and research on SCI. CONCLUSION: There is the need to reflect on the conceptualization and operationalization of interactivity on consumer health websites. Interactions between different users can make these websites important platforms for promoting self-management of chronic conditions, organizational innovation, and participatory research. PRACTICE IMPLICATIONS: Interactivity on consumer health websites is a main resource for health communication. Health organizations are invited to build interactive websites, by considering, however, that the exploitation of interactivity require users' collaboration, processes and standards for managing content, creating and translating knowledge, and conducting internet-based studies. PMID- 24215944 TI - Slowly progressive folate-deficiency myelopathy: report of a case. AB - BACKGROUND: Folate deficiency is known to be associated with subacute combined degeneration of the spinal cord; however, reports of long-standing cases are rare. Although neurological deficits due to folate deficiency have been reported to respond to folic acid supplementation, the functional outcomes have not been fully elucidated. OBJECTIVE: The aim of the study was to evaluate the clinical features and response to folate supplementation in a patient with folate deficiency manifested over 10 years as a slowly progressive myelopathy. METHODS: We performed comprehensive clinical screening, electrophysiological testing, and posturography before and after folate supplementation. RESULTS: A 49-year-old man had a slowly progressive gait disturbance for 10 years. He had not eaten fresh green vegetables for more than 10 years. Neurological examination revealed spastic paraplegia and absence of any vibration sense in the lower limbs accompanied by a positive Romberg's sign. Serum folate level was low, and plasma homocysteine level was elevated. Levels of blood thiamine and serum cobalamin were normal. We diagnosed the patient with myelopathy due to folate deficiency. Folic acid supplementation led to improvement of his symptoms; posturography and walking speed tests showed partial improvement, while the somatosensory-evoked potentials and central motor conduction time remained unchanged. CONCLUSIONS: Folate deficiency should be considered as a differential diagnosis of chronic slowly progressive myelopathy. The present case suggests the importance of early diagnosis and treatment before the adverse neurological manifestations of folate deficiency become irreversible. PMID- 24215945 TI - Non-paraneoplastic voltage-gated calcium channels antibody-mediated cerebellar ataxia responsive to IVIG treatment. AB - Non-paraneoplastic cerebellar ataxia associated with voltage-gated calcium channel (VGCC) antibodies is a rare entity with only few cases reported in literature. We describe a 60 year-old man with subacute cerebellar ataxia and subclinical Lambert-Eaton myasthenic syndrome (LEMS) in whom VGCC antibodies were detected at high titer in serum and cerebrospinal fluid. Screening for underlying malignancies was negative. Intravenous immunoglobulin treatment led to the improvement of clinical picture and reduction of serum antibody titer over a 13 month follow-up period. We emphasize that VGCC antibodies should be included in the diagnostic work-up of patients with subacute cerebellar ataxia and that treatment with IVIG can improve the clinical picture and prevent disability. PMID- 24215947 TI - Time well spent: the duration of foster care and early adult labor market, educational, and health outcomes. AB - Individuals who spent time in foster care as children fare on average worse than non-placed peers in early adult life. Recent research on the effect of foster care placement on early adult life outcomes provides mixed evidence. Some studies suggest negative effects of foster care placement on early adult outcomes, others find null effects. This study shows that differences in the average duration of foster care stays explain parts of these discordant findings and then test how foster care duration shapes later life outcomes using administrative data on 7220 children. The children experienced different average durations of foster care because of differences in exposure to a reform. Later born cohorts spent on average 3 months longer in foster care than earlier born cohorts. Isolating exogenous variation in duration of foster care, the study finds positive effects of increased duration of foster care on income and labor market participation. PMID- 24215946 TI - Hypothiocyanous acid oxidation of tubulin cysteines inhibits microtubule polymerization. AB - Thiol oxidation is a probable outcome of cellular oxidative stress and is linked to degenerative disease progression. In addition, protein thiol redox reactions are increasingly identified as a mechanism to regulate protein structure and function. We assessed the effect of hypothiocyanous acid on the cytoskeletal protein tubulin. Total cysteine oxidation by hypothiocyanous and hypochlorous acids was monitored by labeling tubulin with 5-iodoacetamidofluorescein and by detecting higher molecular weight inter-chain tubulin disulfides by Western blot under nonreducing conditions. Hypothiocyanous acid induced nearly stoichiometric oxidation of tubulin cysteines (1.9 mol cysteine/mol oxidant) and no methionine oxidation was observed. Because disulfide reducing agents restored all the polymerization activity that was lost due to oxidant treatment, we conclude that cysteine oxidation of tubulin inhibits microtubule polymerization. Hypothiocyanous acid oxidation of tubulin cysteines was markedly decreased in the presence of 4% glycerol, a component of the tubulin purification buffer. Due to its instability and buffer- and pH-dependent reactivity, hypothiocyanous acid studies require careful consideration of reaction conditions. PMID- 24215948 TI - Developmental trajectories of romantic stages and associations with problem behaviours during adolescence. AB - Normative romantic development is theorized to progress through a series of stages: affiliative activities, group-based dating, and romantic relationships. The objectives of this research were threefold: empirically examine this progression of romantic stages during adolescence, determine normative and atypical trajectories, and examine links with internalizing and externalizing symptoms. An eight-wave longitudinal study was conducted with 698 adolescents (53.6% female; M(age) = 11.8 years at start of study). A group-based trajectory approach was employed to identify prototypical trajectories of romantic development and a model with three distinct romantic trajectories (i.e., On-time, Early Starters and Late Bloomers) was identified. Both timing and sequencing of romantic activity differed among trajectory groups. Analysis of Variance (ANOVAs) identified associations between Early Starters and externalizing behaviours in early, middle and later adolescence. The findings support progression through theorized stages of romantic activity and highlight the problems that are linked to early-starting and non-sequenced romantic development. PMID- 24215949 TI - The impact of sleep on adolescent depressed mood, alertness and academic performance. AB - The present study developed and tested a theoretical model examining the inter relationships among sleep duration, sleep quality, and circadian chronotype and their effect on alertness, depression, and academic performance. Participants were 385 adolescents aged 13-18 years (M = 15.6, SD = 1.0; 60% male) were recruited from eight socioeconomically diverse high schools in South Australia. Participants completed a battery of questionnaires during class time and recorded their sleep patterns in a sleep diary for 8 days. A good fit was found between the model and the data (chi(2)/df = 1.78, CFI = .99, RMSEA = .04). Circadian chronotype showed the largest association with on adolescent functioning, with more evening-typed students reporting worse sleep quality (beta = .50, p < .001) and diminished alertness (beta = .59, p < .001). Sleep quality was significantly associated with poor outcomes: adolescents with poorer sleep quality reported less sleep on school nights (beta = -.28, p < .001), diminished daytime alertness (beta = .33, p < .001), and more depressed mood (beta = .47, p < .001). Adolescents with poor sleep quality and/or more evening chronotype were also more likely to report worse grades, through the association with depression. Sleep duration showed no direct effect on adolescent functioning. These results identified the importance of two lesser-studied aspects of sleep: circadian chronotype and sleep quality. Easy-to-implement strategies to optimize sleep quality and maintain an adaptive circadian body clock may help to increase daytime alertness, elevate mood, and improve academic performance. PMID- 24215950 TI - Brief report: youth pathways out of homelessness - preliminary findings. AB - While there exists an extensive body of knowledge regarding the risks associated with youth homelessness, very little work has addressed the process of exiting street contexts. This paper reports baseline findings from an ongoing longitudinal study assessing factors associated with a successful transition out of homelessness. Fifty-one formerly homeless youth who obtained stable housing in the past 2 months to 2 years participated in this study which took place in two Canadian urban centres. Findings include poorer functioning across all domains for youth residing in housing contexts without supports, a lack of relationship between psychological and behavioural aspects of community integration, and the central role of self-concept in mental health and quality of life. These findings suggest the need for ongoing support for youth exiting street spaces and social contexts, with attention to the importance of self-concept and psychological aspects of community integration. PMID- 24215951 TI - Mothers' marital history and the physical and mental health of young adults: an investigation over the early life course. AB - Using survey data from 12,424 adolescents and their mothers over 13 years in the nationally representative National Longitudinal Study of Adolescent Health, the purpose of this study was to examine a life course model exploring the pathways linking mothers' marital history (identified as latent classes) and young adult health outcomes. During young adulthood (Wave 4), respondents ranged in age from 19 to 32. The results demonstrated unique long-term influences of stressful marital history typologies of mothers (prior to 1995) on the physical and mental health of young adults (2008) with reference to consistently married mothers after controlling for health status in 2001. These influences operated through family processes (economic pressure and parental rejection) and adolescent psychosocial adjustment (self-esteem, academic performance, and delinquent behavior). Our findings show that vulnerable groups of youth, in terms of mothers' marital history, can be identified early for appropriate intervention efforts. PMID- 24215952 TI - The role of gender and race in the relation between adolescent distress tolerance and externalizing and internalizing psychopathology. AB - Distress tolerance (DT) is an established construct contributing to the onset and maintenance of psychopathology in adulthood; however, few studies have examined the role of DT in older adolescent psychopathology. Emerging data suggest that gender and race may influence this relation. Therefore, the current study examined the relation between gender, race, and DT on parent-reported internalizing and externalizing DSM-oriented symptoms among a community sample of 128, 14-18 year old adolescents. Results indicated a moderating effect of gender on affective problems, such that females with low DT, but not males, displayed significantly greater affective problems. Findings also indicated a significant moderating effect of race, such that Caucasians with low DT, but not African Americans, displayed significantly higher somatic, oppositional defiant, and conduct problems. These findings suggest that DT is an important clinical variable in older adolescence, particularly among Caucasians and females. PMID- 24215954 TI - Brief report: the adolescent Child-to-Parent Aggression Questionnaire: an examination of aggressions against parents in Spanish adolescents. AB - The objective of this study was to develop a questionnaire to assess child-to parent aggression in adolescents and to document the extent of the problem. The questionnaire developed in this study, the Child-to-Parent Aggression Questionnaire (CPAQ), includes forms of physical and psychological aggression directed at both the mother and the father. It also includes open questions about the reasons for the aggressive acts. The CPAQ was completed by a sample of 2719 adolescents (age range: 13-18 years old, 51.4% girls). Confirmatory factor analysis supported a four-factor correlated structure (physical aggression against mother, physical aggression against father, psychological aggression against mother, and psychological aggression against father). Psychological and physical aggression against the mother was more frequent than against the father. However, there were no differences with regard to severe forms of aggression. Girls scored significantly higher on all indicators of psychological aggression, including severe psychological aggression. Nevertheless, except for the prevalence of physical aggression against mothers, which was higher in females, there were no significant differences in physical aggression against parents. Finally, the reasons provided by the adolescents for the aggression included both instrumental (e.g., to obtain permission to get home late and to access their computers) and reactive reasons (e.g., anger and self-defense). These findings highlight the complexity of child-to-parent aggression in adolescence. PMID- 24215953 TI - Internalizing symptoms and rumination: the prospective prediction of familial and peer emotional victimization experiences during adolescence. AB - Adolescence is marked by increases in stressful life events. Although research has demonstrated that depressed individuals generate stress, few studies investigate the generation of emotional victimization. The current study examined the effects of rumination and internalizing symptoms on experiences of peer victimization and familial emotional abuse. Participants were 216 adolescents (M = 14-years-old; 58% female; 47% African-American) who completed two assessments. Results showed that rumination predicted peer victimization and emotional abuse. The effect of rumination on emotional victimization is heightened for those who have higher levels of depression symptoms. That is, individuals who ruminate and who have depression symptoms experience increases in both peer emotional victimization and parental emotional abuse. This study builds upon prior research and indicates that rumination may be a stronger predictor of emotional victimization than symptoms of depression or anxiety. Identifying underlying mechanisms may yield targets for interventions aimed at addressing the chronic nature of depression. PMID- 24215955 TI - Addressing career barriers for high risk adolescent girls: the PATHS curriculum intervention. AB - The study evaluated a gender-specific comprehensive career development curriculum designed to target career barriers faced by high risk adolescent girls - those with disabilities and at risk for school failure. The goal of the curriculum was to promote social cognitive career and self determination outcomes associated with adaptive career development and adjustment. A pre-post control group design was used to evaluate the curriculum. Findings suggest that participation in the curriculum resulted in significant and large gains in autonomy and in disability and gender-related knowledge. Meaningful gains were noted in perceptions of social support and relevance of school. Participants in a high fidelity sample made significant and large gains in vocational skills self-efficacy and disability and gender-related knowledge. Meaningful improvements were noted in self-advocacy, autonomy, and vocational outcome expectations. The findings suggest that the curriculum can improve important indicators of positive career development and adjustment in high risk adolescent girls. PMID- 24215956 TI - Warm and harsh parenting as mediators of the relation between maternal and adolescent emotion regulation. AB - Maternal hostility/rejection and warmth were considered as potential mediators of the relation between mothers' and adolescents' emotion regulation. Participants were first-year high school students living in Ankara, Turkey and their mothers (N = 365). Scales assessing emotion regulation difficulties and maternal hostility/rejection and warmth were administered to both the adolescents and their mothers. Maternal hostility/rejection, but not warmth, mediated the relation between maternal and adolescent emotion regulation. For girls there was, additionally, a direct effect of maternal emotion regulation. The different roles played by parental rejection and parental warmth in the development of adolescents' emotion regulation accord with arguments that socialization occurs in different domains and that rejection and warmth are not aspects of the same domain. PMID- 24215957 TI - Sleep patterns and psychological functioning in families in northeastern Iran; evidence for similarities between adolescent children and their parents. AB - Sleep and well-being of adolescents and their parents are related, but data from non-Western countries are scarce. The aim of the present study was to investigate the relationship between adolescents' and their parents' sleep patterns and psychological functioning in northeastern Iran. A total of 81 families (81 mothers, 78 fathers, 130 children aged 12-20 years) took part in the study. They individually and separately completed questionnaires related to sleep and psychological functioning. Sleep quality was related within families. Poor sleep among children and parents was related in each case to more depressive symptoms and stress. Mothers' sleep and psychological functioning were more related to adolescent children's sleep and psychological functioning than were those of fathers. Results confirm research showing that adolescent's and parents' sleep and psychological functioning are inter-related. This association holds also true for families in northeastern Iran, suggesting that the association reflects universal features of family functioning. PMID- 24215958 TI - International note: temperament and character's relationship to subjective well being in Salvadorian adolescents and young adults. AB - The present study investigated the relationship between personality and Subjective Well-Being in a sample of 135 Salvadorian adolescents and young adults (age mean = 21.88 sd. = 4.70). Personality was assessed through self-reports using the Temperament and Character Inventory-Revised. Subjective Well-Being was also self-reported using the Positive Affect Negative Affect Schedule and the Satisfaction With Life Scale. Structural equation modeling was used to determine relationships between personality and Subjective Well-Being. Regarding temperament dimensions, Harm Avoidance was positively associated to negative affect and negatively associated to positive affect, while Persistence was positively associated to positive affect. Regarding character dimensions, only Self-directedness was related to Subjective Well-Being: positively related to life satisfaction and positive affect. The results presented here mirror findings using the temperament and character model of personality among European and North American adolescents. PMID- 24215960 TI - Overall and unique similarities between parents' values and adolescent or emerging adult children's values. AB - The transmission of values between generations has gained more and more research interest over the last few years. One important outcome of the process of value transmission is the degree of similarity between parents and their children, that may vary across child's developmental stages. This study aimed to estimate the cultural stereotype effect on parent-child value similarity in adolescence and in emerging adulthood. Participants were 423 Italian fathers, mothers, and their adolescent (56.7%) or emerging adult (43.3%) children, who were asked to fill out the Portrait Values Questionnaire. Parent-child value similarity was small in size among families with adolescents, and significantly higher among families with emerging adults. Nevertheless, after removing stereotype effects, this difference disappeared, suggesting that the higher parent-emerging adult value similarity was to a great extent socially derived. Implications of this finding were discussed. PMID- 24215961 TI - Exposure to life adversity in high school and later work participation: a longitudinal population-based study. AB - This paper investigates whether exposure to violence, sexual abuse, or bullying is associated with later work participation and whether high school completion has a potential mediating role. Self-reported junior high school questionnaire data were linked for eight consecutive years to prospective registry data for the demographics, educational progress, employment activity, and social benefits of 11,874 individuals. Ordinal regression analysis showed that violence and/or bullying at 15 years of age predicted negative work participation outcomes eight years later, independent of high school completion and other relevant factors. Although increasing educational level may have some preventive effect, these results indicate that prevention efforts should be initiated at an early age and should target adverse life experiences. PMID- 24215959 TI - Are sexual media exposure, parental restrictions on media use and co-viewing TV and DVDs with parents and friends associated with teenagers' early sexual behaviour? AB - Sexual content in teenagers' media diets is known to predict early sexual behaviour. Research on sexual content has not allowed for the social context of media use, which may affect selection and processing of content. This study investigated whether sexual media content and/or contextual factors (co-viewing, parental media restrictions) were associated with early sexual behaviour using 2251 14-15 year-olds from Scotland, UK. A third (n = 733) reported sexual intercourse. In multivariable analysis the likelihood of intercourse was lower with parental restriction of sexual media and same-sex peer co-viewing; but higher with mixed-sex peer co-viewing. Parental co-viewing, other parental restrictions on media and sexual film content exposure were not associated with intercourse. Findings suggest the context of media use may influence early sexual behaviour. Specific parental restrictions on sexual media may offer more protection against early sex than other restrictions or parental co-viewing. Further research is required to establish causal mechanisms. PMID- 24215962 TI - Testing the Index of Problematic Online Experiences (I-POE) with a national sample of adolescents. AB - This article assesses the utility of the Index of Problematic Online Experiences (I-POE) in a national sample of adolescents in the United States. The study was based on a cross-sectional national telephone survey of 1560 Internet users, ages 10 through 17. Data were collected between August, 2010 and January, 2011. The I POE is an 18-item binary response index which can be used to assess problematic internet use across multiple behaviors and activities. Exploratory and confirmatory factor analysis supported a revised index with two factors: a 9-item "excessive use" scale and a 9-item "online social and communication problems" scale among this population. The I-POE showed favorable psychometric properties including adequate internal consistency for the overall scale and for the two subscales. Scores correlate with offline emotional and behavioral difficulties and the I-POE could have value for use as a part of broad mental health assessment procedures in clinical or school settings. PMID- 24215963 TI - Self-concept in adolescence: a longitudinal study on reciprocal effects of self perceptions in academic and social domains. AB - Fostering social and academic self-concepts are central educational goals. During mid-adolescence academic engagement and success seem to be devalued by peers and to be negatively associated with students' social standing. For this age group, is the development of a positive academic self-concept compatible with the development of a positive social self-concept? We investigated relations among academic self-concept, social self-concept, and academic achievement. 1282 students (47.60% female) participated in three-waves of measurement in Grade 5, 6, and 8. Earlier social self-concept of acceptance negatively predicted changes in academic self-concept over time while earlier social self-concept of assertion positively predicted changes in academic self-concept. There were no significant relations between social self-concepts and achievement but positive reciprocal relations between academic self-concept and achievement. Results indicate that fostering adolescents self-concept in social and academic domains are compatible goals. However, some students need support in managing the challenge to coordinate social and academic goals. PMID- 24215964 TI - Making a difference in adult-child relationships: evidence from an adult-child communication intervention in Botswana, Malawi, and Mozambique. AB - Girls are vulnerable to HIV in part because the social systems in which they live have failed to protect them. This study evaluates a program aimed at strengthening adult-child relationships to reduce girls' vulnerability to HIV in Botswana, Malawi, and Mozambique. In addition to an extensive process evaluation, a cross-sectional post-intervention survey was conducted in the three countries. The total sample size was 1418 adolescent girls (ages 11-18). Bivariate and multilevel, multivariate analyses were conducted to assess the association between adult program exposure and adult-child relationship improvement. In Botswana, Malawi, and Mozambique, girls whose mothers and fathers participated in the program, as compared to those whose parents did not participate in the program, were significantly more likely to report that their relationships with their parents had improved. Research has shown the important role that adults can play in the mitigation of youth risk taking behavior. PMID- 24215965 TI - Happiness and health behaviour in Iranian adolescent girls. AB - This study was conducted to examine the association of happiness in adolescent females with leisure time and health related behaviours namely diet, physical activity and first or second hand smoking. Using a self-administered questionnaire, data were collected from 8159 female high school students ages 11 19 years. Multivariate linear regression analysis revealed statistically significant associations between happiness and weight, regular exercise, exposure to second-hand tobacco smoke, daily fruit or vegetable consumption and the way participants spent their leisure time. Happiness was associated with lower BMI, regular physical activity, absence of exposure to second-hand smoke, higher consumption of fruits and vegetables, and spending leisure time with family (all P < 0.005). These exploratory findings suggest that encouraging children and adolescents to adopt healthy behaviours, providing family time and a smoke-free environment may make them not only healthier but also happier. PMID- 24215966 TI - Developmental trajectories of religiosity, sexual conservatism and sexual behavior among female adolescents. AB - Understanding the role of socio-sexual cognitions and religiosity on adolescent sexual behavior could guide adolescent sexual health efforts. The present study utilized longitudinal data from 328 young women to assess the role of religion and socio-sexual cognitions on sexual behavior accrual (measuring both coital and non-coital sexual behavior). In the final triple conditional trajectory structural equation model, religiosity declined over time and then increased to baseline levels. Additionally, religiosity predicted decreased sexual conservatism and decreased sexual conservatism predicted increased sexual behavior. The final models are indicative of young women's increasing accrual of sexual experience, decreasing sexual conservatism and initial decreasing religiosity. The results of this study suggest that decreased religiosity affects the accrual of sexual experience through decreased sexual conservatism. Effective strategies of sexual health promotion should include an understanding of the complex role of socio-sexual attitudes with religiosity. PMID- 24215967 TI - Coming of age on the streets: survival sex among homeless young women in Hollywood. AB - This study examined childhood physical or sexual abuse, involvement in dependency or delinquency systems, psychiatric hospitalization, and suicide as possible risk factors for survival sex among homeless young women. Homeless young women were found to have similarly high rates of childhood sexual abuse, dependency and delinquency systems involvement, and psychiatric hospitalization. Homeless young women involved in survival sex disclosed higher rates of attempted suicide and reported marginally higher rates of childhood physical abuse. Analysis of qualitative data showed that those engaged in survival sex were motivated primarily by desperation to meet basic needs including a place to stay, food and money, and one third mentioned that peers commonly were influential in decisions to engage in survival sex. Others were influenced by coercion (10%) or pursuit of drugs (10%). Young women engaged in survival sex generally experienced regret and shame about their experience. PMID- 24215968 TI - The measurement of reflective function in adolescents with and without borderline traits. AB - Reflective function refers to the capacity to reflect on the mind of self and others in the context of the attachment relationship. Reflective function (and its conceptual neighbor, mentalizing) has been shown to be an important correlate of a variety of disorders, including borderline personality disorder (BPD). The current study examined the construct validity of the Reflective Function Questionnaire for Youths (RFQY) in an inpatient sample of adolescents. Adequate internal consistency was established for the RFQY. Significant positive associations with an interview-based measure of reflective function and an experimental-based assessment of mentalization were found for the RFQY. Strong negative relations with BPD features were found and adolescent patients who scored above clinical cut-off for BPD symptoms demonstrated significantly poorer reflective function compared to patients without the disorder. These findings provide preliminary support for the notion that reflective function can be validly and reliably assessed in adolescent populations. PMID- 24215969 TI - Suicidal ideations and attempts among adolescents subjected to childhood sexual abuse and family conflict/violence: the mediating role of anger and depressed mood. AB - Based on a sample of 9085 16- to 19-year-old students attending all high schools in Iceland in 2004, the current study examines depressed mood and anger as potential mediators between family conflict/violence and sexual abuse, on the one hand, and suicidal ideations and suicide attempts on the other. Agnew's general strain theory provides the theoretical framework for the study. Structural equation modelling (SEM) was conducted allowing explicit modelling of both direct and mediating effects using observed and latent variables. The findings showed that both depressed mood and anger mediated the relationship between family conflict/violence and sexual abuse and suicidal attempts. However, when testing the mediating pathways between sexual abuse and family conflict/violence and suicidal ideations, only depressed mood but not anger turned out to be a significant mediator. The authors discuss how these finding may inform and facilitate the design and development of interventions to reduce the likelihood of suicide attempts among young people. PMID- 24215970 TI - Comparing reports of peer rejection: associations with rejection sensitivity, victimization, aggression, and friendship. AB - Perceiving that one is rejected is an important correlate of emotional maladjustment. Yet, self-perceptions can substantially differ from classmate reports of who is rejected. In this study, discrepancies between self- and classmate-reports of rejection were identified in 359 Australian adolescents (age 10-12 years). As expected, adolescents who overestimated rejection reported more rejection sensitivity and felt more victimized by their peers, but were not seen by peers as more victimized. Adolescents who underestimated rejection identified themselves as high in overt aggression, and their peers identified them as high in overt and relational aggression and low in prosocial behavior. Yet, underestimators' feelings of friendship satisfaction did not seem to suffer and they reported low rejection sensitivity. Results suggest that interventions to promote adolescent health should explicitly recognize the different needs of those who do and do not seem to perceive their high rejection, as well as adolescents who overestimate their rejection. PMID- 24215971 TI - Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. AB - BACKGROUND: Early recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda. METHODS: A retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10. RESULTS: Of 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 - 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 - 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95% CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95% CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients. CONCLUSIONS: One in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure. PMID- 24215972 TI - Understanding systemic problems in providing mental health services to people with an intellectual disability and co-morbid mental disorders in Victoria. AB - OBJECTIVE: This paper explores the difficulties the services system in Victoria has in responding to people with intellectual disability (ID) and mental health problems and identifies the underlying assumptions that have led to these. These issues are discussed and where possible put into a Victorian context with the intention of informing service development in the area of Dual Disability (co morbid mental disorders in people with intellectual disability). CONCLUSIONS: People with ID have high levels of mental health need. Generic services have difficulty responding to these needs due to a range of patient, professional and service system factors as well as some of the conceptual issues underpinning policy and legislation. PMID- 24215973 TI - Neural mechanisms supporting the extraction of general knowledge across episodic memories. AB - General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a hippocampo-neocortical dialog, as proposed previously for system-level consolidation. To test these hypotheses, we assessed possible differences in consolidation between associative memories containing cross-episodic regularities and unique associative memories. Subjects learned face-location associations, half of which responded to complex regularities regarding the combination of facial features and locations, whereas the other half did not. Importantly, regularities could only be extracted over hippocampus-encoded, associative aspects of the items. Memory was assessed both immediately after encoding and 48 h later, under fMRI acquisition. Our results suggest that processes related to system-level reorganization occur preferentially for regular associations across episodes. Moreover, the build-up of general knowledge regarding regular associations appears to involve the coordinated activity of the hippocampus and mediofrontal regions. The putative cross-talk between these two regions might support a mechanism for regularity extraction. These findings suggest that the consolidation of cross-episodic regularities may be a key mechanism underlying general knowledge acquisition. PMID- 24215974 TI - Does experience in talking facilitate speech repetition? AB - Speech is unique among highly skilled human behaviors in its ease of acquisition by virtually all individuals who have normal hearing and cognitive ability. Vocal imitation is essential for acquiring speech, and it is an important element of social communication. The extent to which age-related changes in cognitive and motor function affect the ability to imitate speech is poorly understood. We analyzed the distributions of response times (RT) for repeating real words and pseudowords during fMRI. The average RT for older and younger participants was not different. In contrast, detailed analysis of RT distributions revealed age dependent differences that were associated with changes in the time course of the BOLD response and specific patterns of regional activation. RT-dependent activity was observed in the bilateral posterior cingulate, supplementary motor area, and corpus callosum. This approach provides unique insight into the mechanisms associated with changes in speech production with aging. PMID- 24215975 TI - Effect of prenatal methamphetamine exposure and challenge dose of the same drug in adulthood on epileptiform activity induced by electrical stimulation in female rats. AB - Our previous study demonstrated that chronic prenatal methamphetamine (MA) exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats. As seizures are known to be dependent on sex and female estrous cycle, the goal of the present study was to examine the combined effect of prenatal MA exposure (5mg/kg) and the MA challenge dose (1mg/kg) in adulthood on electroencephalography (EEG) recordings and consequences of brain stimulation in freely moving adult female rats with respect to the estrous cycle. Overall, 12 groups of adult female rats were tested: prenatally MA exposed, prenatally saline-exposed and rats without prenatal injections, each of these groups was either postnatally challenged with MA or with saline injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S) and further divided according to the stage of the estrous cycle to metestrus/diestrus (M/D) or proestrus/estrus (P/E). Seizures were induced by repetitive electrical stimulation (15s/8Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SADs) were evaluated. Additionally, behavior associated with stimulation and ADs, and occurrence of wet-dog-shakes (WDS) were analyzed. The present study demonstrates that the prenatal MA exposure decreased the seizure threshold in females in M/D, but not in females in P/E. In addition, prenatally MA-exposed M/D females injected with saline in adulthood had increased the duration of ADs as well as SADs. The challenge dose of MA also decreased the seizure threshold. Moreover, prenatal as well as adult MA administration decreased the number and occurrence of WDS, respectively. Thus, the present study demonstrates that the effect of prenatal MA exposure and challenge dose of the same drug on focally induced epileptiform activity in adult female rats depends on the estrous cycle. PMID- 24215976 TI - Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling. AB - Progesterone is a known anticonvulsant, with its inhibitory effects generally attributed to its secondary metabolite, 5alpha,3alpha-tetrahydroprogesterone (THP), and THP's enhancement of GABAA receptor activity. Accumulating evidence, however, suggests that progesterone may have non-genomic actions independent of the GABAA receptor. In this study, we explored THP/GABAA-independent anticonvulsive actions of progesterone in a mouse model of hippocampal kindling and in mouse entorhinal slices in vitro. Specifically, we examined the effects of progesterone in kindled mice with or without pretreatments with finasteride, a 5alpha-reductase inhibitor known to block the metabolism of progesterone to THP. In addition, we examined the effects of progesterone on entorhinal epileptiform potentials in the presence of a GABAA receptor antagonist picrotoxin and finasteride. Adult male mice were kindled via a daily stimulation protocol. Electroencephalographic (EEG) discharges were recorded from the hippocampus or cortex to assess "focal" or "generalized" seizure activity. Kindled mice were treated with intra-peritoneal injections of progesterone (10, 35, 100 and 160mg/kg) with or without finasteride pretreatment (50 or 100mg/kg), THP (1, 3.5, 10 and 30mg/kg), midazolam (2mg/kg) and carbamazepine (50mg/kg). Entorhinal cortical slices were prepared from naive young mice, and repetitive epileptiform potentials were induced by 4-aminopyridine (100MUM), picrotoxin (100MUM) and finasteride (1MUM). Pretreatment with finasteride did not abolish the anticonvulsant effects of progesterone. In finasteride-pretreated mice, progesterone at 100 and 160mg/kg decreased cortical but not hippocampal afterdischarges (ADs). Carbamazepine mimicked the effects of progesterone with finasteride pretreatments in decreasing cortical discharges and motor seizures, whereas midazolam produced effects similar to progesterone alone or THP in decreasing hippocampal ADs and motor seizures. In brain slices, progesterone at 1MUM inhibited entorhinal epileptiform potentials in the presence of picrotoxin and finasteride. We suggest that progesterone may have THP/GABAA-dependent and independent anticonvulsive actions in the hippocampal-kindled mouse model. PMID- 24215978 TI - Expression of beta1- and beta2-adrenoceptors in different subtypes of interneurons in the medial prefrontal cortex of mice. AB - Noradrenaline acting via beta-adrenoceptors (beta-ARs) in the CNS plays an important role in learning/memory and cognitive functions. beta-ARs have been shown to be expressed in cortical pyramidal and subcortical principal cells. However, little is known about beta-AR expression in different subtypes of GABAergic neurons. Here, we report that both beta1- and beta2-ARs are expressed in a majority of GABAergic interneurons in the medial prefrontal cortex of mice, including parvalbumin (PV)-, calretinin (CR)-, calbindin D-28k (CB)-, somatostatin (SST)- and Reelin-immunoreactive (ir) interneurons. Relative to PV-, CB-, SST- and Reelin-ir interneurons, CR-ir interneurons are less likely to express beta1- and beta2-ARs. SST-ir interneurons are more likely to express beta2-AR compared with the other subtypes of interneurons. The present results are of significance for understanding the role of beta-ARs in prefrontal cortical functions. PMID- 24215977 TI - Differential cortical neurotrophin and cytogenetic adaptation after voluntary exercise in normal and amnestic rats. AB - Voluntary exercise (VEx) has profound effects on neural and behavioral plasticity, including recovery of CNS trauma and disease. However, the unique regional cortical adaption to VEx has not been elucidated. In a series of experiments, we first examined whether VEx would restore and retain neurotrophin levels in several cortical regions (frontal cortex [FC], retrosplenial cortex [RSC], occipital cortex [OC]) in an animal model (pyrithiamine-induced thiamine deficiency [PTD]) of the amnestic disorder Wernicke-Korsakoff syndrome. In addition, we assessed the time-dependent effect of VEx to rescue performance on a spontaneous alternation task. Following 2-weeks of VEx or stationary housing conditions (Stat), rats were behaviorally tested and brains were harvested either the day after VEx (24-h) or after an additional 2-week period (2-wk). In both control pair-fed (PF) rats and PTD rats, all neurotrophin levels (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and vascular endothelial growth factor) increased at the 24-h period after VEx in the FC and RSC, but not OC. Two-weeks following VEx, BDNF remained elevated in both FC and RSC, whereas NGF remained elevated in only the FC. Interestingly, VEx only recovered cognitive performance in amnestic rats when there was an additional 2-wk adaptation period after VEx. Given this unique temporal profile, Experiment 2 examined the cortical cytogenetic responses in all three cortical regions following a 2-wk adaptation period after VEx. In healthy (PF) rats, VEx increased the survival of progenitor cells in both the FC and RSC, but only increased oligodendrocyte precursor cells (OLPs) in the FC. Furthermore, VEx had a selective effect of only recovering OLPs in the FC in PTD rats. These data reveal the therapeutic potential of exercise to restore cortical plasticity in the amnestic brain, and that the FC is one of the most responsive cortical regions to VEx. PMID- 24215979 TI - GABA-induced uncoupling of GABA/benzodiazepine site interactions is mediated by increased GABAA receptor internalization and associated with a change in subunit composition. AB - Persistent activation of GABAA receptors triggers compensatory changes in receptor function that are relevant to physiological, pathological and pharmacological conditions. Chronic treatment of cultured neurons with GABA for 48h has been shown to produce a down-regulation of receptor number and an uncoupling of GABA/benzodiazepine site interactions with a half-time of 24-25h. Down-regulation is the result of a transcriptional repression of GABAA receptor subunit genes and depends on activation of L-type voltage-gated calcium channels. The mechanism of this uncoupling is currently unknown. We have previously demonstrated that a single brief exposure of rat primary neocortical cultures to GABA for 5-10min (t1/2=3min) initiates a process that results in uncoupling hours later (t1/2=12h) without a change in receptor number. Uncoupling is contingent upon GABAA receptor activation and independent of voltage-gated calcium influx. This process is accompanied by a selective decrease in subunit mRNA levels. Here, we report that the brief GABA exposure induces a decrease in the percentage of alpha3-containing receptors, a receptor subtype that exhibits a high degree of coupling between GABA and benzodiazepine binding sites. Initiation of GABA induced uncoupling is prevented by co-incubation of GABA with high concentrations of sucrose suggesting that it is dependent on a receptor internalization step. Moreover, results from immunocytochemical and biochemical experiments indicate that GABA exposure causes an increase in GABAA receptor endocytosis. Together, these data suggest that the uncoupling mechanism involves an initial increase in receptor internalization followed by activation of a signaling cascade that leads to selective changes in receptor subunit levels. These changes might result in the assembly of receptors with altered subunit compositions that display a lower degree of coupling between GABA and benzodiazepine sites. Uncoupling might represent a homeostatic mechanism that negatively regulates GABAergic transmission under physiological conditions in which synaptic GABAA receptors are transiently activated for several minutes. PMID- 24215980 TI - Glial cell line-derived neurotrophic factor (GDNF) expression and NMJ plasticity in skeletal muscle following endurance exercise. AB - Glial cell line-derived neurotrophic factor (GDNF) supports and maintains the neuromuscular system during development and through adulthood by promoting neuroplasticity. The aim of this study was to determine if different modes of exercise can promote changes in GDNF expression and neuromuscular junction (NMJ) morphology in slow- and fast-twitch muscles. Rats were randomly assigned to a run training (run group), swim training (swim group), or sedentary control group. GDNF protein content was determined by enzyme-linked immunosorbant assay. GDNF protein content increased significantly in soleus (SOL) following both training protocols (P<0.05). Although not significant, an increase of 60% in the extensor digitorum longus (EDL) followed swim-training (NS; P<0.06). NMJ morphology was analyzed by measuring alpha-bungarotoxin labeled post-synaptic end plates. GDNF content and total end plate area were positively correlated. End plate area decreased in EDL of the run group and increased in SOL of the swim group. The results indicate that GDNF expression and NMJ morphological changes are activity dependent and that different changes may be observed by varying the exercise intensity in slow- and fast-twitch fibers. PMID- 24215982 TI - Patient information on breast reconstruction in the era of the world wide web. A snapshot analysis of information available on youtube.com. AB - Breast cancer patient's expectation and choice of reconstruction is increasing and patients often satisfy their information needs outside clinic time by searching the world wide web. The aim of our study was to analyse the quality of content and extent of information regarding breast reconstruction available on YouTube videos and whether this is an appropriate additional source of information for patients. A snapshot qualitative and quantitative analysis of the first 100 videos was performed after the term 'breast reconstruction' was input into the search window of the video sharing website www.youtube.com on the 1st of September 2011. Qualitative categorical analysis included patient, oncological and reconstruction factors. It was concluded that although videos uploaded onto YouTube do not provide comprehensive information, it is a useful resource that can be utilised in patient education provided comprehensive and validated videos are made available. PMID- 24215983 TI - Primary and secondary distant metastatic breast cancer: two sides of the same coin. AB - OBJECTIVES: This study evaluated the differences between breast cancer (BC) patients who present with primary distant metastatic disease (PMD) and those who develop distant metastases during the course of their illness (secondary metastatic disease [SMD]) with regard to clinicopathological characteristics, patterns of metastatic sites, palliative therapy and survival. PATIENTS & METHODS: Based on a cohort of patients with newly diagnosed BC (n = 1459), we analyzed all patients who had PMD (n = 92, 6.3%) and those who developed SMD (n = 277, 20.3%). RESULTS: There were no significant differences with regard to the patient's age in which metastatic disease had been diagnosed (PMD/SMD: 64 years/66 years, p = 0.19). The SMD group had more often triple-negative carcinomas (25.5%/7.3%, p = 0.019); there were no significant differences with regard to grading (p = 0.61), HER2 status (p = 0.67) and hormonal receptor status (p = 1.00). The mean number of metastatic locations was similar (2.3/2.3, p = 0.91). While patients with PMD usually initiated systemic therapy, patients with SMD received systemic therapy after diagnosis of metastatic disease less often (16.4%/2.6%, p < 0.001). Both groups received palliative chemotherapy similarly often (PMD/SMD: 62.8%/63.3%, p = 1.00). The mean number of palliative therapy lines was similar (PMD/SMD: 2.8/3.2, p = 0.39). Compared to patients with SMD, patients who had PMD had a significantly improved metastatic disease survival (p < 0.001). The one-year, two-year and five-year survival rates were as follows: 76.9%/60.3%, 58.2%/43.0%, 23.1%/10.6%. The median survival times were 18.5 months and 32 months. CONCLUSION: The poorer prognosis of patients with SMD may be explained by differences in clinicopathological features of the tumor, metastatic patterns, the use palliative therapy and drug resistance of the tumor cells which occurs in therapy-naive PMD patients at a later phase of the disease course. PMID- 24215981 TI - Ingestion of bacterial lipopolysaccharide inhibits peripheral taste responses to sucrose in mice. AB - A fundamental role of the taste system is to discriminate between nutritive and toxic foods. However, it is unknown whether bacterial pathogens that might contaminate food and water modulate the transmission of taste input to the brain. We hypothesized that exogenous, bacterially-derived lipopolysaccharide (LPS), modulates neural responses to taste stimuli. Neurophysiological responses from the chorda tympani nerve, which innervates taste cells on the anterior tongue, were unchanged by acute exposure to LPS. Instead, neural responses to sucrose were selectively inhibited in mice that drank LPS during a single overnight period. Decreased sucrose sensitivity appeared 7days after LPS ingestion, in parallel with decreased lingual expression of Tas1r2 and Tas1r3 transcripts, which are translated to T1R2+T1R3 subunits forming the sweet taste receptor. Tas1r2 and Tas1r3 mRNA expression levels and neural responses to sucrose were restored by 14 days after LPS consumption. Ingestion of LPS, rather than contact with taste receptor cells, appears to be necessary to suppress sucrose responses. Furthermore, mice lacking the Toll-like receptor (TLR) 4 for LPS were resistant to neurophysiological changes following LPS consumption. These findings demonstrate that ingestion of LPS during a single period specifically and transiently inhibits neural responses to sucrose. We suggest that LPS drinking initiates TLR4-dependent hormonal signals that downregulate sweet taste receptor genes in taste buds. Delayed inhibition of sweet taste signaling may influence food selection and the complex interplay between gastrointestinal bacteria and obesity. PMID- 24215984 TI - Emerging nanotherapeutic strategies in breast cancer. AB - Nanoparticle-based drug delivery platforms are emerging as powerful chemotherapeutic modalities in breast cancer. Doxorubicin and paclitaxel nanoparticle formulations are currently used clinically, yielding distinct pharmacokinetic parameters that prolong blood circulation times, enhance drug accumulation in tumors, and limit adverse side effects to patients. And while these nanoconstructs have shown substantial improvements in patient tolerability and survival, several emerging trends stand to make a significant impact on future generations of nanoparticle platforms for breast cancer therapy. Firstly, there is a heightened understanding of several processes involved in tumor growth, potentiation, and invasion, resulting in the identification of several attractive molecular targets. This in turn has given rise to antibody-based therapeutics, drug repositioning, and the burgeoning field of RNA interference (RNAi). Secondly, an enhanced understanding of transport phenomena involved in delivery of chemotherapeutics has led to a rethinking and retooling of nanoscale drug carrier designs. Nanoparticle platforms are now incorporating features meant to overcome biological barriers and enhance drug accumulation within tumors, all the while incorporating unique chemistries that enable for controlled release of therapeutic payloads. This review aims to detail the current clinical state of nanoparticle-based therapeutics in breast cancer, as well as highlight several platforms that exemplify the future generation of innovative approaches to chemotherapy in breast cancer. PMID- 24215985 TI - Erythrocyte membrane cholesterol and lipid core growth in a rabbit model of atherosclerosis: modulatory effects of rosuvastatin. AB - BACKGROUND: Lipid core expansion is partly responsible for the conversion of a stable atherosclerotic lesion to a rupture-prone plaque. Intraplaque hemorrhage contributes to the accumulation of cholesterol within unstable plaques. In the present study, we investigated, using a rabbit model of atherosclerosis, the extent to which diet-induced increases in cholesterol content of erythrocyte membranes (CEM) contribute to lipid core expansion and the modulatory effect of rosuvastatin use. METHODS AND RESULTS: Rabbits fed with atherogenic diet (0.75% cholesterol) for 5 months exhibited advanced atherosclerotic lesions (mean plaque area, 0.39 +/- 0.03 mm(2)), and lipid core size was associated with the concentration-time integral (CTI) of CEM levels (r=0.567, P=0.004) independent of other established predictors of lipid core size. Further experiments were performed by feeding rabbits atherogenic diet (1% cholesterol) for 3 months, followed by either normal diet or normal diet plus rosuvastatin for the next 3 months. Although no differences were observed in total plaque area between both groups, administration of rosuvastatin was associated with significantly smaller lipid cores, fewer macrophages within the lipid core, less microvessels as well as with lower CTI of CEM levels compared to normal diet alone. Moreover, intraplaque erythrocyte membranes covered a smaller lipid core area in rabbits under rosuvastatin plus normal diet as opposed to rabbits under diet alone. CONCLUSIONS: Increased CEM levels, induced by high-cholesterol diet, are associated with lipid core growth. Ingestion of a potent HMG-CoA reductase inhibitor (rosuvastatin) may decrease CEM levels, and this effect may contribute to regression of the lipid core. PMID- 24215986 TI - Temporal texture of associative encoding modulates recall processes. AB - Binding aspects of an experience that are distributed over time is an important element of episodic memory. In the current study, we examined how the temporal complexity of an experience may govern the processes required for its retrieval. We recorded event-related potentials during episodic cued recall following pair associate learning of concurrently and sequentially presented object-picture pairs. Cued recall success effects over anterior and posterior areas were apparent in several time windows. In anterior locations, these recall success effects were similar for concurrently and sequentially encoded pairs. However, in posterior sites clustered over parietal scalp the effect was larger for the retrieval of sequentially encoded pairs. We suggest that anterior aspects of the mid-latency recall success effects may reflect working-with-memory operations or direct access recall processes, while more posterior aspects reflect recollective processes which are required for retrieval of episodes of greater temporal complexity. PMID- 24215987 TI - A verified spider bite and a review of the literature confirm Indian ornamental tree spiders (Poecilotheria species) as underestimated theraphosids of medical importance. AB - Literature on bird spider or tarantula bites (Theraphosidae) is rare. This is astonishing as they are coveted pets and interaction with their keepers (feeding, cleaning the terrarium or taking them out to hold) might increase the possibility for bites. Yet, this seems to be a rare event and might be why most theraphosids are considered to be harmless, even though the urticating hairs of many American species can cause disagreeable allergic reactions. We are describing a case of a verified bite by an Indian ornamental tree spider (Poecilotheria regalis), where the patient developed severe, long lasting muscle cramps several hours after the bite. We present a comprehensive review of the literature on bites of these beautiful spiders and conclude that a delayed onset of severe muscle cramps, lasting for days, is characteristic for Poecilotheria bites. We discuss Poecilotheria species as an exception from the general assumption that theraphosid bites are harmless to humans. PMID- 24215988 TI - [Treatment of primary bone lymphomas]. AB - Primary bone lymphoma constitutes a rare entity. They are often localized. The studies published are retrospective, using definitions and different classifications. The populations of the studied patients are often heterogeneous. The therapeutic modalities used are also different. Consequently, the prognostic stratification and the analysis of the therapeutic results are difficult. We review the literature and discuss the therapeutic modalities and the results as well as the prognosis of the primary bone lymphomas. PMID- 24215989 TI - Honorary authorship: frequency and associated factors in physical medicine and rehabilitation research articles. AB - OBJECTIVES: To estimate the prevalences of perceived honorary authorship and International Committee of Medical Journal Editors (ICMJE)-defined honorary authorship, and identify factors affecting each rate in the physical medicine and rehabilitation literature. DESIGN: Internet-based survey. SETTING: Not applicable. PARTICIPANTS: First authors of articles published in 3 major physical medicine and rehabilitation journals between January 2009 and December 2011 were surveyed in June and July 2012 (N=1182). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The reported prevalences of perceived and ICMJE-defined honorary authorship were the primary outcome measures, and multiple factors were analyzed to determine whether they were associated with these measures. RESULTS: The response rate was 27.3% (248/908). The prevalences of perceived and ICMJE defined honorary authorship were 18.0% (44/244) and 55.2% (137/248), respectively. Factors associated with perceived honorary authorship in the multivariate analysis included the suggestion that an honorary author should be included (P<.0001), being a medical resident or fellow (P=.0019), listing "reviewed manuscript" as 1 of the nonauthorship tasks (P=.0013), and the most senior author deciding the authorship order (P=.0469). Living outside North America was independently associated with ICMJE-defined honorary authorship (P=.0079) in the multivariate analysis. In the univariate analysis, indicating that the most senior author decided authorship order was significantly associated with ICMJE-defined honorary authorship (P=<.001). CONCLUSIONS: Our results suggest that honorary authorship does occur in a significant proportion of the physical medicine and rehabilitation literature. Additionally, we found several factors associated with perceived and ICMJE-defined honorary authorship and a discrepancy between the 2 rates. Further studies with larger response rates are recommended to further explore this topic. PMID- 24215990 TI - Honorary authorship. AB - This issue of Archives of Physical Medicine and Rehabilitation includes an article by Rajasekaran et al that addresses the persistent, difficult, and unsettled issue of unwarranted authorship as it applies to physical medicine and rehabilitation. The findings that it exists and that its frequency is similar to the 25% to 50% rates reported in other medical specialties are discouraging but, unfortunately, not surprising. They do, however, warrant discussion. This commentary attempts to do so and begins with a review of Rajasekaran's findings. It then proceeds to compare them with other work in the literature and concludes with a discussion of (1) why unwarranted authorship matters; (2) if it matters, why does it matter; and (3) what we as authors, editors, and the publishing world can do about it. Our goal is to give us all an improved understanding of the situation as well a little more backbone when dealing with the pressures associated with both overt and covert suggestions for the inclusion of authors that we may believe are unwarranted. PMID- 24215991 TI - Level of mobility limitations and falls status in persons with multiple sclerosis. AB - OBJECTIVE: To investigate whether fall rates are constant across levels of mobility limitations. DESIGN: Secondary analysis of baseline assessments from a stratified randomized controlled trial. SETTING: Community. PARTICIPANTS: Persons with multiple sclerosis (N=365) were divided into 5 groups based on the mobility section of the Guy's Neurological Disability Scale (GNDS): no walking impairment (n=82); impaired walking, no aid (n=87); unilateral support (n=76); bilateral support to walk (n=78); or occasional wheelchair user (n=42). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-reported fall history (ie, retrospective) in the preceding 3 months. RESULTS: One hundred twenty-four persons in the overall sample reported falling in the last 3 months (fall prevalence, 33.97%). Of the total sample, 17.8% reported 2 or more falls in the last 3 months. Chi square analysis revealed a significant difference in the proportion of fallers across GNDS categories (chi(2)=42.64, P<.001). Post hoc analysis revealed that the group who walked with bilateral support had the greatest proportion of fallers (52.6%), while the group without walking impairment had the lowest proportion (15.9%). An examination of recurrent fallers as a function of group found that there were more recurrent fallers (70%) in the group that had a walking impairment but used no aid, relative to the other groups. CONCLUSIONS: The current findings highlight that fall rates including recurrent fall prevalence are not uniform across mobility aid categories in persons with MS. Those using bilateral assistance for gait have the highest prevalence of fallers, and those with walking limitations and not yet using an aid had the greatest prevalence of multiple falls. PMID- 24215992 TI - Humeral head reconstruction for Hill-Sachs defects: a biomechanical comparison of 2 fixation techniques for bone grafting. AB - PURPOSE: The purpose of this biomechanical study was to compare anterograde with retrograde screw fixation for allograft reconstruction of Hill-Sachs defects. METHODS: In 8 pairs of fresh-frozen humeral heads, a 40% Hill-Sachs defect was created. The resultant wedge-shaped osteochondral fragment was used as allograft. For each technique, two 3.75-mm screws were used for fixation. To test the strength of fixation, a custom tool was used that would apply load to the graft. By use of a materials testing machine, a staircase cyclic loading protocol was performed (500 cycles at 10, 20, 30, and 40 N) and then load to failure. Graft displacement was measured by an optical tracking system. RESULTS: For the 2 techniques, graft displacement increased with increasing load and increasing number of cycles up to a mean of 0.9 +/- 0.42 mm for anterograde fixation and 1.1 +/- 0.79 mm for retrograde fixation. This increase was significant within each technique across all 4 loading levels (P < .05). However, there were no significant differences in graft displacement between the 2 techniques at any loading level or number of cycles (P = .16 to P = .96). In addition, the load to failure between the anterograde and retrograde techniques (98.5 N and 95.6 N, respectively) was not significantly different (P = .706). CONCLUSIONS: The initial fixation and failure strength of anterograde and retrograde graft fixation techniques for substantial Hill-Sachs defects do not significantly differ in a biomechanical cadaveric model. CLINICAL RELEVANCE: This biomechanical study supports that in an engaging Hill-Sachs defect, both anterograde and retrograde screw fixation techniques can be used for fixation of humeral head allografts. PMID- 24215993 TI - 70 degrees frontal visualization of lateral compartment of the elbow allows extensor carpi radialis brevis tendon release with preservation of the radial lateral collateral ligament. AB - PURPOSE: To determine whether the radial component of the lateral collateral ligament (R-LCL) and extensor carpi radialis brevis (ECRB) are consistently visible, using a 70 degrees arthroscope, as parallel structures in the extra articular space of the elbow, and to evaluate the clinical outcomes of these techniques in a series of patients. METHODS: An arthroscopic ECRB tendon release was performed between 2008 and 2010. Eighteen patients were retrospectively evaluated at a minimum of 24 months' follow-up. The surgeon performed the ECRB release while protecting the R-LCL and viewing the structures extra-articularly with a 70 degrees arthroscope through the anteromedial portal. Patients underwent surgery if they presented with localized tenderness and pain not responding to conservative treatment for 12 months and had magnetic resonance imaging scans indicating tendinopathy or degeneration. Arthritis, posterolateral rotatory instability, trauma, and previous surgeries were exclusion criteria. Intraoperative videos were reviewed and a clinical examination was performed by an independent reviewer at 24 months postoperatively. Patients were also evaluated with the Mayo Elbow Performance Score; Andrews-Carson score; and shortened Disabilities of the Arm, Shoulder and Hand questionnaire. Direct varus stress was applied in extension and flexion (40 degrees ), and the posterolateral pivot-shift and chair tests were performed. RESULTS: Visualization with the 70 degrees arthroscope through the anteromedial portal was successful in all of the cases (100%). Visualization of the residual ECRB tendon stump, as well as the posterior common extensor tendon, was also achieved 94% of the time. The final mean Mayo Elbow Performance Score and Andrews-Carson score were 82.5 (range, 60 to 100) and 185.3 (range, 125 to 200), respectively. The mean postoperative score on the shortened Disabilities of the Arm, Shoulder and Hand questionnaire was 20.14 (range, 5 to 57.5). Clinical tests showed stability in all the cases. CONCLUSIONS: The 70 degrees arthroscope allows visualization of the ECRB insertion and R-LCL frontally and in parallel. A surgical plane could be created between the structures. The clinical outcome was good or excellent in 78% of the cases. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 24215995 TI - Physiological energetics of the fourth instar of Chinese horseshoe crabs (Tachypleus tridentatus) in response to hypoxic stress and re-oxygenation. AB - Hypoxia associated with eutrophication is a potential threat to the Chinese horseshoe crab Tachypleus tridentatus which inhabits intertidal sand flats in Asia. This study investigated the effect of dissolved oxygen level (DO) (6, 4 and 2 mg O2 l(-1)) on the physiological energetics in the juvenile T. tridentatus. They were exposed to various oxygen levels for three days and then transferred to normoxia for three days to examine the recovery from low oxygen stress. Feeding rate, respiration rate and scope for growth were reduced at lower DO levels while absorption efficiency and excretion rate were independent of DO levels. Although full recovery of the physiological responses and scope for growth from hypoxis stress was observed when normoxia resumed, their long term survival in suboptimal habitats with frequent occurrence of hypoxia deserves a close monitoring as hypoxia may be even more common in future in a warming world. PMID- 24215996 TI - Metal concentrations and detoxification mechanisms in Solea solea and Solea senegalensis from NW Mediterranean fishing grounds. AB - The common sole, Solea solea and the Senegalese sole, Solea senegalensis are two important commercial species that coexist in the NW Mediterranean Sea. The present field survey was designed to assess the role of kidney in metal handling and detoxification in the two sole species collected at six fishing grounds along the Catalan coast. Metallothionein (MT) and selenium (Se) were analysed in relation to toxic metal loads in kidney as potential protective mechanisms. Acetylcholinesterase (AChE) and lactate dehydrogenase (LDH) activities as well as lipid peroxidation (LP) levels were measured in several tissues as general markers of toxicity. AChE was measured in brain muscle and gills, LDH in plasma and LP in muscle and gills. The protective role of MT and Se was indicated by the positive correlations with Hg and Cd levels as well as with the high Se:Hg ratio, in a species-dependent way. Principal Component Analysis (PCA) considering all chemical and biomarker variables discriminated individuals collected at the different fishing grounds. PMID- 24215997 TI - Homology modeling and docking studies of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum. AB - (+) Gamma-lactamases are enantioselective hydrolysis enzymes that can be used to produce optically pure (-) gamma-lactam, an important pharmaceutical intermediate for the anti-AIDS drug Abacavir. In this study, homology modeling and molecular dynamic simulation studies of a 3D homology model of BjGL, a novel (+) gamma lactamase from Bradyrhizobium japonicum, were constructed and refined. The specific substrate (+) gamma-lactam and its enantiomer (-) gamma-lactam which can not be hydrolyzed was docked into the active site respectively, and the catalytic triad and other crucial residues that participate in the formation of the hydrophobic binding pocket, hydrogen bonds, and the oxyanion hole were identified. Furthermore, possible reasons for the high diastereoselectivity of BjGL binding with the substrate are proposed. PMID- 24215999 TI - Foreword to the special issue on LASCON 2012. PMID- 24215998 TI - Insight into the interaction between DNA bases and defective graphenes: covalent or non-covalent. AB - Although some metal clusters and molecules were found to more significantly bind to defective graphenes than to pristine graphenes, exhibiting chemisorptions on defective graphenes, the present investigation shows that the adsorption of DNA bases on mono- and di-vacant defective graphenes does not show much difference from that on pristine graphene, and is still dominantly driven by noncovalent interactions. In the present study the adsorptions of the nucleobases, adenine (A), cytosine (C), guanine, (G), and thymine (T) on pristine and defective graphenes, are fully optimized using a hybrid-meta GGA density functional theory (DFT), M06-2X/6-31G*, and the adsorption energies are then refined with both M06 2X and B97-D/6-311++G**. Graphene is modeled as nano-clusters of C72H24, C71H24, and C70H24 for pristine, mono- and di-vacant defective graphenes, respectively, supplemented by a few larger ones. The result shows that guanine has the maximum adsorption energy in all of the three adsorption systems; and the sequence of the adsorption strength is G>A>T>C on the pristine and di-vacant graphene and G>T>A>C on the mono-vacant graphene. In addition, the binding energies of the DNA bases with the pristine graphene are less than the corresponding ones with di-vacant defective graphene; however, they are greater than those of mono-vacant graphene with guanine and adenine, while it is dramatic that the binding energies of mono vacant graphene with thymine and cytosine appear larger than those of pristine graphene. PMID- 24216000 TI - Safety and effectiveness of the GenousTM endothelial progenitor cell-capture stent in the first year following ST-elevation acute myocardial infarction: A single center experience and review of the literature. AB - PURPOSE: The GenousTM stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies. METHODS AND MATERIALS: All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. RESULTS: In the cohort of 109 patients (73.4% male, 59 +/- 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50-4.00) and median length of 15 mm (9-33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy. CONCLUSIONS: GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data. SUMMARY: We report the safety and effectiveness of the GenousTM stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction. PMID- 24216001 TI - Perforated Sinus of Valsalva (PSOV) aneurysm closure with a muscular VSD occluder. AB - We report a case of a Perforated Sinus of Valsalva Aneurysm (PSOV) closure using an Amplatzer muscular ventricular septal defect occluder (mVSD) device and describe a novel and potentially safer way for defect sizing. A literature review of the endovascular treatment of this disease is presented. PMID- 24216002 TI - Levothyroxin replacement therapy restores hypothyroidism induced impairment of L LTP induction: critical role of CREB. AB - Cyclic-AMP response element binding protein (CREB) is a transcription factor crucial for late phase long-term potentiation (L-LTP) induction and maintenance. Upon multiple high frequency stimulation (MHFS), large Ca(2+) influx activates adenylyl cyclase. This, in turn, activates PKA, which by itself or through MAPK p42/p44 can activate (phosphorylate) CREB. Upon phosphorylation, P-CREB activates multiple genes essential for L-LTP generation. Calcium calmodulin kinase IV (CaMKIV) is also activated by calcium and can directly activate CREB. We have shown previously that hypothyroidism impairs L-LTP and reduces the basal protein levels of CREB, MAPK p42/p44, and CaMKIV in area CA1 of the hippocampus. In the present study, levels of these signaling molecules were determined in area CA1 during the induction and maintenance phases of L-LTP. Standard MHFS was used to evoke L-LTP in the CA1 area of hypothyroid, levothyroxin treated hypothyroid and sham control anesthetized adult rats. Chronic levothyroxin treatment reversed hypothyroidism-induced L-LTP impairment. Five minutes after MHFS, western blotting showed an increase in the levels of P-CREB, and P-MAPK p42/p44 in sham operated control, and levothyroxin treated hypothyroid animals, but not in hypothyroid animals. The protein levels of total CREB, total MAPK p42/p44, BDNF and CaMKIV were not altered in all groups five minutes after MHFS. Four hours after MHFS, the levels of P-CREB, and P-MAPK p42/p44 remained unchanged in hypothyroid animals, while they were elevated in sham-operated control, and levothyroxin treated hypothyroid animals. We conclude that respective normalized phosphorylation of essential kinases such as P-CREB and P-MAPK p42/p44 is correlated with restoration of normal L-LTP induction and maintenance in the CA1 area of levothyroxin-treated hypothyroid animals. PMID- 24216003 TI - Female mate choice in convict cichlids is transitive and consistent with a self referent directional preference. AB - INTRODUCTION: One of the most important decisions that an animal has to make in its life is choosing a mate. Although most studies in sexual selection assume that mate choice is rational, this assumption has not been tested seriously. A crucial component of rationality is that animals exhibit transitive choices: if an individual prefers option A over B, and B over C, then it also prefers A over C. RESULTS: We assessed transitivity in mate choice: 40 female convict cichlids had to make a series of binary choices between males of varying size. Ninety percent of females showed transitive choices. The mean preference index was significantly higher when a female chose between their most preferred and least preferred male (male 1 vs. male 3) compared to when they chose between males of adjacent ranks (1 vs. 2 or 2 vs. 3). The results are consistent with a simple underlying preference function leading to transitive choice: females preferred males about one third larger than themselves. This rule of thumb correctly predicted which male was preferred in 67% of the cases and the ordering in binary choices in 78% of cases. CONCLUSIONS: This study provides the first evidence for strong stochastic transitivity in a context of mate choice. The females exhibited ordinal preferences and the direction and magnitude of these preferences could be predicted from a simple rule. The females do not necessarily compare two males to choose the best; it is sufficient to use a self-referent evaluation. Such a simple decision rule has important implications for the evolution of the mating strategies and it is consistent with patterns of assortative mating repeatedly observed at population level. PMID- 24216004 TI - Pituitary ACTH-secreting adenoma in Addison's disease: a case report. PMID- 24216005 TI - Concurrent asymptomatic inflammatory aneurysm and ischemic stroke due to cysticercal arteritis. PMID- 24216006 TI - Interactions of chromatic and lens-induced defocus during visual control of eye growth in guinea pigs (Cavia porcellus). AB - It was recently demonstrated that chromaticity could affect eye growth and refractive development in guinea pigs but it remained unclear whether correction with spectacle lenses could balance these effects and how retinal responses change with different spectral compositions of light. Three illumination conditions were tested: blue, red and white light. Animals were raised without or with monocular spectacle lenses from three to seven weeks of age. Luminance electroretinograms (ERGs) were recorded to explore retinal responses with the different spectral compositions. In our special colony of pigmented guinea pigs, characterized by residual hyperopia, spontaneous myopia and poor emmetropization, red light induced early thinning of the choroid and relative myopia, compared to white light. Effects of red light could not be suppressed if positive spectacle lenses were worn. ERGs showed that red light failed to elicit robust retinal responses. Blue light inhibited axial eye growth, even when animals were reared with negative lenses. Intensity-matched blue and white light elicited similar a waves but different b-waves, suggesting that the wavelength of light affects visual control of eye growth through different processing in the inner retina. We hypothesize that blue light might stimulate preferentially the ON pathway to inhibit myopia induced by negative lenses, at least in guinea pigs. PMID- 24216007 TI - The role of the foreshortening cue in the perception of 3D object slant. AB - Slant is the degree to which a surface recedes or slopes away from the observer about the horizontal axis. The perception of surface slant may be derived from static monocular cues, including linear perspective and foreshortening, applied to single shapes or to multi-element textures. It is still unclear the extent to which color vision can use these cues to determine slant in the absence of achromatic contrast. Although previous demonstrations have shown that some pictures and images may lose their depth when presented at isoluminance, this has not been tested systematically using stimuli within the spatio-temporal passband of color vision. Here we test whether the foreshortening cue from surface compression (change in the ratio of width to length) can induce slant perception for single shapes for both color and luminance vision. We use radial frequency patterns with narrowband spatio-temporal properties. In the first experiment, both a manual task (lever rotation) and a visual task (line rotation) are used as metrics to measure the perception of slant for achromatic, red-green isoluminant and S-cone isolating stimuli. In the second experiment, we measure slant discrimination thresholds as a function of depicted slant in a 2AFC paradigm and find similar thresholds for chromatic and achromatic stimuli. We conclude that both color and luminance vision can use the foreshortening of a single surface to perceive slant, with performances similar to those obtained using other strong cues for slant, such as texture. This has implications for the role of color in monocular 3D vision, and the cortical organization used in 3D object perception. PMID- 24216008 TI - Contour interaction in foveal vision: a response to Siderov, Waugh, and Bedell (2013). PMID- 24216009 TI - Identification of three new Alu Yb subfamilies by source tracking of recently integrated Alu Yb elements. AB - BACKGROUND: Alu elements are the most abundant mobile elements in the human genome, with over 1 million copies and constituting more than 10% of the genome. The majority of these Alu elements were inserted into the primate genome 35 to 60 million years ago, but certain subfamilies of Alu elements are relatively very new and suspected to be still evolving. We attempted to trace the source/master copies of all human-specific members of the Alu Yb lineage using a computational approach by clustering similar Yb elements and constructing an evolutionary relation among the members of a cluster. RESULTS: We discovered that one copy of Yb8 at 10p14 is the source of several active Yb8 copies, which retrotransposed to generate 712 copies or 54% of all human-specific Yb8 elements. We detected eight other Yb8 elements that had generated ten or more copies, potentially acting as 'stealth drivers'. One Yb8 element at 14q32.31 seemed to act as the source copy for all Yb9 elements tested, having producing 13 active Yb9 elements, and subsequently generated a total of 131 full-length copies. We identified and characterized three new subclasses of Yb elements: Yb8a1, Yb10 and Yb11. Their copy numbers in the reference genome are 75, 8 and 16. We analysed personal genome data from the 1000 Genome Project and detected an additional 6 Yb8a1, 3 Yb10 and 15 Yb11 copies outside the reference genome. Our analysis indicates that the Yb8a1 subfamily has a similar age to Yb9 (1.93 million years and 2.15 million years, respectively), while Yb10 and Yb11 evolved only 1.4 and 0.71 million years ago, suggesting a linear evolutionary path from Yb8a1 to Yb10 and then to Yb11. Our preliminary data indicate that members in Yb10 and Yb11 are mostly polymorphic, indicating their young age. CONCLUSIONS: Our findings suggest that the Yb lineage is still evolving with new subfamilies being formed. Due to their very young age and the high rate of being polymorphic, insertions from these young subfamilies are very useful genetic markers for studying human population genetics and migration patterns, and the trend for mobile element insertions in the human genome. PMID- 24216010 TI - Responding to Australia's National Hepatitis B Strategy 2010-13: gaps in knowledge and practice in relation to Indigenous Australians. AB - The Australian National Hepatitis B Strategy 2010-13 outlines five priority areas for developing a comprehensive response to the hepatitis B virus (HBV): building partnerships and strengthening community action; preventing HBV transmission; optimising diagnosis and screening; clinical management of people with chronic hepatitis B (CHB); and developing health maintenance, care and support for people with HBV. A scoping study was used to map the main sources and types of evidence available on the epidemiology and natural history of HBV among Indigenous Australians as well as public health responses published since 2001 (January 2001 May 2013). Gaps in current knowledge were identified. While the literature documents the success of universal infant immunisation and indicates the potential for screening initiatives to identify infected and susceptible individuals, prevalence of CHB and hepatocellular cancer remain high in Indigenous Australians. Significant gaps in knowledge and practice were identified in relation to each of the five National Hepatitis B Strategy priority action areas. Successful implementation of the strategy in Indigenous communities and reducing the burden of HBV and hepatocellular cancer in Indigenous Australians will require increased investment in research and knowledge transfer across all priority areas. PMID- 24216011 TI - [How to write a medical report for the assessment of disability]. AB - The present article revises practical aspects on the format and content of the clinical reports used for the evaluation of disability for the Spanish Disability Grants System. As a framework for understanding how these clinical reports should be, the review includes also a short overview of the different types of disability grants and the administrative and court mechanisms for granting. PMID- 24216012 TI - [Spanish validation of the MacArthur Competence Assessment Tool for Treatment interview to assess patients competence to consent treatment]. AB - BACKGROUND AND OBJECTIVE: To validate the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) Spanish version, which assesses the mental capacity of patients to consent treatment, by examining 4 areas (Understanding, Appreciation, Reasoning and Expressing a choice). PATIENTS AND METHOD: SAMPLE: 160 subjects (80 Internal Medicine inpatients, 40 Psychiatric inpatients and 40 healthy controls). INSTRUMENTS: MacCAT-T, Mini-Mental Status Examination (MMSE). PROCEDURE: Feasibility study, reliability and validity calculations (against to gold standard of clinical expert). RESULTS: Mean duration of the MacCAT-T interview was 18min. Inter-rater reliability: Intraclass correlation coefficient for Understanding=0.98, Appreciation=0.97, Reasoning=0.98, Expressing a choice=0.91. Internal consistency (Cronbach's alpha): Understanding=0.87, for Appreciation=0.76, for Reasoning=0.86. Patients considered to be incapable (gold standard) scored lower in all the MacCAT-T areas. Poor performance on the MacCAT T was related to cognitive impairment assessed by MMSE. CONCLUSIONS: Spanish version of the MacCAT-T is feasible, reliable, and valid for assessing the capacity of patients to consent treatment. PMID- 24216013 TI - [Risk of pharmacological interactions due to the co-administration of statins and cytochrome P450 isoenzyme 3A4-metabolized drugs: multicentre, crossover study]. AB - BACKGROUND AND OBJECTIVES: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions. PATIENTS AND METHODS: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed. RESULTS: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions. CONCLUSION: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives. PMID- 24216014 TI - [Pharmacogenetic use in clinical practice: treatment of pain]. PMID- 24216015 TI - [Is it posible to reduce the human immunodeficiency virus-associated chronic inflammation?]. PMID- 24216016 TI - [Use of laser for the prevention and treatment of oral mucositis induced by radiotherapy and chemotherapy for head and neck cancer]. AB - One of the complications of radiotherapy and chemotherapy is oral mucositis. Since the low energy laser is one of the most frequently recommended interventions by authors and international societies, the aim of this study is to review the scientific evidence on the use of lasers as a preventive and therapeutic in oral mucositis associated with treatment of cancer. We performed a literature search in PubMed and The Cochrane Collaboration Library, limiting the search to the last 20 years. We finally included 29 articles that contained 30 studies. Low energy laser phototherapy seems a promising intervention in both the prevention and treatment of oral mucositis associated with cancer treatment. Virtually all studies reviewed showed good results with no adverse effects and reductions in both incidence and severity of mucositis in all types of cancer treatments. PMID- 24216017 TI - [Usefulness of cystatin C as a prognostic marker in venous thromboembolism]. AB - BACKGROUND AND OBJECTIVE: Cystatin C (cysC) is a prognostic marker in patients with hypertension, coronary heart disease and heart failure. The aim of this study was to determine the prognostic value of cysC levels obtained at the time of diagnosis in patients with venous thromboembolism (VTE). MATERIAL AND METHOD: Retrospective study of a cohort of 226 consecutive patients with VTE, followed for 6 months. Serum samples were obtained for the determination of cysC, creatinine, and the N-terminal fraction of the brain natriuretic peptide (NT proBNP) at the time of diagnosis. RESULTS: The highest discriminating power value of dying at 6 months for cysC was 1,175mg/dl (sensitivity 76%, specificity 65%, positive predictive value 26%, negative predictive value 94%). Above the cut-off, 17/48 patients died, versus 9/152 that had lower levels (odds ratio: 5.98, 95% confidence interval [95% CI]: 2.50-14.29, P<.001). The adjusted hazard ratio in a multivariate model was 3.76 (95% CI 1.46-9.66). The accuracy of this parameter was similar to that for creatinine (1.24mg/dl) but lower than the NT-proBNP (435pg/ml). Patients who exceeded the limit values of cysC and NT-proBNP together had no greater risk of death than those above NT-proBNP only (odds ratio: 9.43, 95% CI 3.90-22.81, P<.001). There was no value, which was significantly associated with bleeding episodes or recurrent thromboembolism. CONCLUSION: CysC concentration at the time of diagnosis in VTE patients has prognostic value, which is similar to that of serum creatinine and lower than that of NT-proBNP. PMID- 24216018 TI - [Relationship between vitamin D deficiency and metabolic syndrome]. AB - BACKGROUND AND OBJECTIVE: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. PATIENTS AND METHODS: We undertook a population based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. RESULTS: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25 hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25 hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age. CONCLUSIONS: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome. PMID- 24216019 TI - Massive difference in synonymous substitution rates among mitochondrial, plastid, and nuclear genes of Phaeocystis algae. AB - We are just beginning to understand how mutation rates differ among mitochondrial, plastid, and nuclear genomes. In most seed plants the mitochondrial mutation rate is estimated to be lower than those of the plastid and nucleus, whereas in the red alga Porphyra the opposite is true, and in certain green algae all three genomes appear to have similar rates of mutation. Relative rate statistics of organelle vs nuclear genes, however, are lacking for lineages that acquired their plastids through secondary endosymbiosis, but recent organelle DNA analyses suggest that they may differ drastically from what is observed in lineages with primary plastids, such as green plants and red algae. Here, by measuring synonymous nucleotide substitutions, we approximate the relative mutation rates within the haptophyte genus Phaeocystis, which has a red algal-derived, secondary plastid. Synonymous-site divergence data indicate that for Phaeocystis antarctica and P. globosa the mitochondrial mutation rate is 10 and 3 times that of the plastid and nucleus, respectively. This differs drastically from relative rate estimates for primary-plastid-bearing lineages and presents a much more dynamic view of organelle vs nuclear mutation rates across the eukaryotic domain. PMID- 24216020 TI - [Paediatric anaesthesia outside the operating theatre suite: the situation in Germany and Quebec]. AB - The authors describe the way pediatric anesthesia is organized outside the operating theatre in their country. In Germany, children can be anesthetized outside the operating theater in the hospital but also outside the hospital according to the concept of office-based anesthesia. National recommendations have been published and their revision is currently underway. In Quebec, pediatric anesthesia outside the operating theatre is well organized in order to ensure quality of care, patient's safety and efficiency of the system. PMID- 24216021 TI - Do people automatically track others' beliefs? Evidence from a continuous measure. AB - Recent findings suggest that tracking others' beliefs is not always effortful and slow, but may rely on a fast and implicit system. An untested prediction of the automatic belief tracking account is that own and others' beliefs should be activated in parallel. We tested this prediction measuring continuous movement trajectories in a task that required deciding between two possible object locations. We independently manipulated whether participants' belief about the object location was true or false and whether an onlooker's belief about the object location was true or false. Manipulating whether or not the agent's belief was ever task relevant allowed us to compare performance in an explicit and implicit version of the same task. Movement parameters revealed an influence of the onlooker's irrelevant belief in the implicit version of the task. This provides evidence for parallel activation of own and others' beliefs. PMID- 24216023 TI - Developing virtual patients for medical microbiology education. AB - The landscape of medical education is changing as students embrace the accessibility and interactivity of e-learning. Virtual patients are e-learning resources that may be used to advance microbiology education. Although the development of virtual patients has been widely considered, here we aim to provide a coherent approach for clinical educators. PMID- 24216022 TI - Decoding the complexity of type I interferon to treat persistent viral infections. AB - Type I interferons (IFN-I) are a broad family of cytokines that are central to the innate immune response. These proteins have long been appreciated for the critical roles they play in restraining viral infections and shaping antiviral immune responses. However, in recent years there has been increased awareness of the immunosuppressive actions of these proteins as well. Although there are many current therapeutic applications to manipulate IFN-I pathways, we have limited understanding of the mechanisms by which these therapies are actually functioning. In this review, we highlight the diversity and temporal impact of IFN-I signaling, discuss the current therapeutic uses of IFN-I, and explore the strategy of blocking IFN-I to alleviate immune dysfunction in persistent virus infections. PMID- 24216024 TI - Oxidoreduction properties of bound ubiquinone in Complex I from Escherichia coli. AB - The exploration of the redox chemistry of bound ubiquinone during catalysis is a prerequisite for the understanding of the mechanism by which Complex I (nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase) transduces redox energy into an electrochemical proton gradient. Studies of redox dependent changes in the spectrum of Complex I from Escherichia coli in the mid- and near ultraviolet (UV) and visible areas were performed to identify the spectral contribution, and to determine the redox properties, of the tightly bound ubiquinone. A very low midpoint redox potential (<-300mV) was found for the bound ubiquinone, more than 400mV lower than when dissolved in a phospholipid membrane. This thermodynamic property of bound ubiquinone has important implications for the mechanism by which Complex I catalyzes proton translocation. PMID- 24216025 TI - Partnerships for health: decimating tuberculosis in the Cook Islands, 1920-1975. AB - How did the Cook Islands manage to achieve a significant reduction in tuberculosis from a high rate in the early 20th century to low rates by 1975? With the mid-century invention of effective drug therapy there was a widespread belief around the Western world that TB could be eradicated. The Cook Islands was one place which almost reached this goal. Based on primary and secondary historical and anthropological research, we argue that the geo-political emplacement of the Cook Islands and development of multi-scale partnerships were crucial to success. Our research indicates the value of understanding and engaging with local community networks and culturally appropriate partnerships in dealing with health issues. PMID- 24216026 TI - Examining the role of location-specific associations between ambient air pollutants and adult asthma in the United States. AB - This study examined the association between ozone and fine particulate (PM2.5) exposure and asthma risk by place of residence. We linked 412,832 adult respondents from the 2009 U.S. Behavioral Risk Factor Surveillance System to their residence counties. Observed and interpolated ozone and PM2.5 concentration data from 2006 to 2009 were used as exposures. We linked self-reported current asthma status and other individual risk factors to county-level risk factors in multilevel logistic regressions. Results indicated spatially varied asthma risks and spatially varied associations between ambient air pollution and asthma risk. Residents in counties not located within a metropolitan statistical area (MSA) and in inner ring suburbs had a relatively higher asthma risk. Positive ozone asthma associations were detected across all spatial settings, while positive PM2.5-asthma associations were detected only in central cities of an MSA and in outer ring suburbs, indicating that residence location modified the relationship between ambient air pollution and asthma risk. PMID- 24216027 TI - Food, eating and body image in the lives of low socioeconomic status rural Mexican women living in Queretaro State, Mexico. AB - Qualitative research using semi-structured interviews and key informant interviews were used to explore how women from low socioeconomic rural households in Queretaro State, Mexico perceived and reacted to their obesogenic environment. Reduced availability of healthy food options and household financial constraints along with reduced agency of women in this setting were factors that limited women's ability to access and consume diets consistent with the promotion of good health. The cultural values that emphasised obesity as a desirable state for women and the women's social networks that promoted these values were also identified as playing a role in reinforcing certain behaviours. Public health advocates wanting to design interventions in such settings need to be sensitive to the cultural as well as the environmental context described for rural Mexican women. PMID- 24216028 TI - British Columbia's pay-for-performance experiment: part of the solution to reduce emergency department crowding? AB - BACKGROUND: Emergency department (ED) overcrowding continues to be a well publicized problem in a number of countries. In British Columbia, a province in Canada, an ED pay-for-performance (ED P4P) program was initiated in 2007 to create financial incentives for hospitals to reduce patients' ED length of stay (ED LOS). This study's objectives are to determine if the ED P4P program is associated with decreases in ED LOS, and to address the ED P4P program's limitations. METHODS: We analyze monthly hospital-level ED LOS time data since the inception of the financial incentives. Since the ED P4P program was phased in at different hospitals from different health authorities over time, hospitals' data from only two regional health authorities are included in the study. RESULTS: We find association between the implementation of ED P4P and ED LOS time data. However, due to the lack of control data, the findings cannot demonstrate causality. Furthermore, our findings are from hospitals in the greater Vancouver area only. INTERPRETATION: BC's ED P4P was introduced to create incentives for hospitals to reduce ED LOS by providing incremental incentive funding. Available data indicate that the ED P4P program is associated with mixed successes in reducing ED LOS among participating hospitals. PMID- 24216029 TI - Ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an HIV-infected patient. AB - Leprosy maybe "unmasked" in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for Hansen's disease, need to be cognizant to this possibility. It may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration. PMID- 24216030 TI - Incidence and progression of cervical lesions in women with HIV: a systematic global review. AB - Global data on cervical lesion incidence and progression in HIV-positive women are essential for understanding the natural history of cervical neoplasia and informing screening policy. A systematic review was performed summarizing the incidence and progression of cervical lesions in HIV-positive women. Of 5882 HIV positive women from 15 studies, incidence ranged from 4.9 to 21.1 cases per 100 woman-years for any cervical lesion and 0.4 to 8.8 cases per 100 woman-years for high-grade cervical lesions. HIV-positive women showed a median three-fold higher incidence of cervical lesions compared to HIV-negative women. Of 1099 HIV positive women from 11 studies, progression from low- to high-grade lesions ranged from 1.2 to 26.2 cases per 100 woman-years. Both incidence and progression rates increased with lower CD4 counts. The effect of antiretroviral therapy on the natural history of cervical neoplasia remains unclear. HIV-positive women have higher incidence and progression of cervical neoplasia. Cervical cancer screening should be integrated into HIV treatment programmes. PMID- 24216031 TI - The role of implementation intention formation in promoting hepatitis B vaccination uptake among men who have sex with men. AB - This study assessed the separate and joint effects of having a goal intention and the completeness of implementation intention formation on the likelihood of attending an appointment to obtain vaccination against the hepatitis B virus among men who have sex with men (MSM) in the Netherlands. Extending previous research, it was hypothesized that to be effective in promoting vaccination, implementation intention formation not only requires a strong goal intention, but also complete details specifying when, where and how to make an appointment to obtain hepatitis B virus vaccination among MSM. MSM at risk for hepatitis B virus (N = 616), with strong or weak intentions to obtain hepatitis B virus vaccination, were randomly assigned to form an implementation intention or not. Completeness of implementation intentions was rated and hepatitis B virus uptake was assessed through data linkage with the joint vaccination registry of the collaborating Public Health Services. Having a strong goal intention to obtain hepatitis B virus vaccination and forming an implementation intention, each significantly and independently increased the likelihood of MSM obtaining hepatitis B virus vaccination. In addition, MSM who formed complete implementation intentions were more successful in obtaining vaccination (p < 0.01). The formation of complete implementation intentions was promoted by strong goal intentions (p < 0.01). PMID- 24216032 TI - Rapid loss of vaccine-acquired hepatitis B surface antibody after three doses of hepatitis B vaccination in HIV-infected persons. AB - HIV-infected individuals have poor responses to hepatitis B vaccine and may have decreased durability of post-vaccination immunity. Retrospective chart review was conducted for HIV-1 positive individuals aged >=18 years who received hepatitis B vaccine at an urban HIV clinic. A total of 309 patients completed three doses and 178 had post-vaccine serology testing after the third dose. In multivariate analysis, time between the third dose and the first post-vaccine serology testing at 180-359 days (OR = 0.077, p = 0.049) and at >=360 days (OR = 0.065, p = 0.019) were associated with poor vaccine responses. A significant decrease in seropositivity appeared as early as 180 days after the third vaccine dose, suggesting a rapid loss of vaccine-acquired hepatitis B surface antibody in HIV infected persons. Our findings suggest that hepatitis B surface antibody should be tested at 6 to 12 months after completing primary vaccine series in order to detect early secondary vaccine failure. PMID- 24216033 TI - Guidance and practice on frequency of HIV and sexually transmitted infection testing in men who have sex with men - what is the European situation? AB - Men who have sex with men (MSM) are at particular risk for HIV/sexually transmitted infections (STI). To investigate the European guidance used for MSM STI and HIV screening, risk level profiling and how this translated to practice, we conducted a questionnaire survey of leading physicians in the European branch of the International Union against Sexually Transmitted Infections (IUSTI). We identified that most European countries have limited guidance on screening intervals for MSM. Where risk profiling is advised, it is often left to clinicians to weight different behaviours and decide on screening frequency. Our results suggest that European MSM STI and HIV testing guidelines be developed with clear and specific recommendations around screening intervals and risk profiling. These guidelines will be particularly helpful due to rapidly evolving models of sexual healthcare, and the emergence of new providers who may benefit from guidelines that require less interpretation. PMID- 24216034 TI - Switching to darunavir/ritonavir monotherapy vs. triple-therapy on body fat redistribution and bone mass in HIV-infected adults: the Monarch randomized controlled trial. AB - Changes in body fat distribution and bone mass in HIV-infected patients may be associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs). The Monarch trial recruited 30 patients receiving non-nucleoside reverse transcriptase inhibitor or protease inhibitor-based highly active antiretroviral therapy, with HIV RNA <40 copies/mL. Patients were randomized to either darunavir/ritonavir 800/100 mg once daily monotherapy or darunavir/ritonavir 800/100 mg once daily + two NRTIs. Bone mass, peripheral lipoatrophy and central fat accumulation were assessed using dual-energy X-ray absorptiometry scanning, supplemented by computed tomography scans. Median age was 43 years, 77% were men. Visceral adipose tissue remained stable from baseline to Week 48 in the whole group (p = 0.261) with no significant difference between arms (p = 0.56). There was a significant reduction in insulin resistance (HOMA-IR, p = 0.013) over 48 weeks in the whole group, but not of body mass index (p = 0.24). In the darunavir/ritonavir monotherapy arm, there was a small but significant increase in both lumbar and femur bone mineral density at 48 weeks and was observed after correction for baseline values. The absolute change in lumbar bone mineral density at 48 weeks was more pronounced in the darunavir/ritonavir arm compared with the darunavir/ritonavir + 2NRTIs arm. In this study, discontinuing nucleoside analogues and switching to darunavir/ritonavir monotherapy was associated with a small but statistically significant increase in bone mineral density, but stable levels of limb fat and visceral adipose tissue. PMID- 24216035 TI - 2012 European guideline for the management of pelvic inflammatory disease. AB - This guideline was produced by the European region of the International Union against sexually transmitted infections (IUSTI) and refers to ascending infections in the female genital tract unrelated to delivery and surgery and does not include actinomyces-related infection. PMID- 24216036 TI - Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors. AB - Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings. PMID- 24216037 TI - Bubonic lymphogranuloma venereum with multidrug treatment failure. AB - A patient with proctitis and inguinal buboes diagnosed with lymphogranuloma venereum (LGV) was treated with doxycycline 21 days, azithromycin 20 days and moxifloxacin for a further 12 days because of progressive worsening of inguinal symptoms. Despite extensive antibiotic treatment, the inguinal LGV lesions persisted; however, the patient recovered spontaneously after three months. PMID- 24216039 TI - 2014 and 2015, two important landmarks on the global health and development agenda. PMID- 24216040 TI - Women's worries in first pregnancy: results from a randomised controlled trial. AB - It has been suggested that participation in an antenatal education programme will increase the level of worry in pregnant women. This randomised controlled trial, investigated women's worries in late pregnancy as a secondary outcome depending on their attendance in an antenatal education programme. We found that women attending the education programme reported a lower level of worry in late pregnancy, especially worries related to birth issues, compared to those who did not attend the antenatal education programme. PMID- 24216038 TI - Lack of evidence for retroviral infections formerly related to chronic fatigue in Spanish fibromyalgia patients. AB - BACKGROUND: The etiology of fibromyalgia and chronic fatigue syndrome (FM/CFS) is currently unknown. A recurrent viral infection is an attractive hypothesis repeatedly found in the literature since it would explain the persistent pain and tiredness these patients suffer from. The initial striking link of two distinct orphan retroviruses: the gamma retroviruses murine leukemia virus (MLV)-related virus and the delta retrovirus T-lymphotropic virus type 2 (HTLV-2) to chronic fatigue have not been confirmed to date. RESULTS: Genomic DNA (gDNA) from 75 fibromyalgia patients suffering from chronic fatigue and 79 age-matched local healthy controls were screened for the presence of MLV-related and HTLV-2 related proviral sequences. The XMRV env gene was amplified in 20% of samples tested (24% patients/15% healthy controls). Unexpectedly, no PCR amplifications from independent gDNA preparations of the same individuals were obtained. None of the positive samples showed presence of contaminating murine sequences previously reported by other investigators, neither contained additional regions of the virus making us conclude that the initial env amplification came from spurious air-driven amplicon contaminants. No specific HTLV-2 sequences were obtained at any time from any of the 154 quality-controlled gDNA preparations screened. CONCLUSIONS: Previous associations between MLV-related or HTLV-2 retrovirus infection with chronic fatigue must be discarded. Thus, studies showing positive amplification of HTLV-2 sequences from chronic fatigue participants should be revised for possible undetected technical problems.To avoid false positives of viral infection, not only extreme precautions should be taken when nested-PCR reactions are prepared and exhaustive foreign DNA contamination controls performed, but also consistent amplification of diverse regions of the virus in independent preparations from the same individual must be demanded.The fact that our cohort of patients did not present evidence of any of the two types of retroviral infection formerly associated to chronic fatigue does not rule out the possibility that other viruses are involved in inciting or maintaining fibromyalgia and/or chronic fatigue conditions. PMID- 24216041 TI - Maternal development experiences of women hospitalized to prevent preterm birth. AB - OBJECTIVE: To examine ways that women's experience of hospitalization with bed rest to prevent preterm birth impacts prenatal maternal development. METHOD: Interviews based on the Interview Schedules for Dimensions of Maternal Development in Psychosocial Adaptation to Pregnancy were conducted at a hospital in the southwestern United States with a convenience sample of 41 women during confinement to bed rest to prevent preterm birth. The interviews were recorded, and verbatim transcripts were submitted to thematic analysis. RESULTS: Five themes were mapped from the women's narratives: (1) acceptance of pregnancy, but with fears specific to elevated risks to self and baby; (2) heightened identification with motherhood and fatherhood protector roles; (3) renewal or deepening of mother-daughter closeness intensified by high-risk pregnancy; (4) enhanced couple support and collaboration; and (5) acceptance of responsibility to perform in remaining pregnant and preparing for labor, but willingness to accept help from doctors and nurses. CONCLUSIONS: This study of hospitalization to prevent preterm birth showed that women experience hospitalization as a burden to be endured to meet future goals, but that it also can facilitate prenatal maternal development in psychosocial adaptation to high risk pregnancy. Implications for research and practice are discussed. PMID- 24216042 TI - An exploration of obese pregnant women's views of being referred by their midwife to a weight management service. AB - Midwives have previously reported concerns about discussing and referring obese pregnant women to weight management services, with some women stating that this referral can be upsetting. The current study interviewed obese women who had declined a weight management service during pregnancy to explore if it was the referral process that made them decline the service. Fifteen women participated and reported that being informed about and referred to a service by their midwife was acceptable to them. Participants also mentioned they would expect this information from their midwife. No participants reported being upset by this referral. PMID- 24216043 TI - Care seeking during the latent phase of labour--frequencies and birth outcomes in two delivery wards in Sweden. AB - OBJECTIVE: To explore the frequency of women seeking care during the latent phase of labour at two delivery wards. Also, to investigate interventions during labour and birth outcomes in relation to parity and remaining in hospital or not during the latent phase. METHODS: A retrospective, population-based cohort study in two delivery wards in Sweden. The sample was based on electronic childbirth records of all births with spontaneous onset. RESULTS: Of 5797 women, 17.6% (n=1023) sought care during the latent phase. Of these, 57.8% (n=591) remained at the hospital, and 50.5% (n=517) had a prolonged latent phase. Nulliparae remaining in hospital had a lower rate of spontaneous vaginal births (p=0.007), more emergency Caesarean sections (CSs) (p<0.001) and more babies with Apgar <7 at 5 min (p=0.045) compared with those returning home. Nulliparae having a prolonged latent phase and remaining in hospital had fewer spontaneous vaginal births (p=0.045), more emergency CSs (p=0.002) and more babies with Apgar <7 at 5 min (p=0.023) compared with those returning home. For multiparous women with a previous vaginal birth, with or without prolonged latent phase, mode of delivery was not influenced by remaining in hospital or not. CONCLUSION: These findings indicate a need for different guidelines for nulliparous and multiparous women seeking hospital care during the latent phase, and for special attention to be given to nulliparous with a prolonged latent phase remaining in hospital during the latent phase. PMID- 24216044 TI - A qualitative study of new fathers' experiences of care in relation to complicated childbirth. AB - OBJECTIVES: The objective of the study was to describe new fathers' experiences with care related to complicated childbirth. METHODS: A qualitative approach consisting of individual interviews using a semi-structured interview guide with open-ended questions was applied. A purposive sample of eight fathers participated. The interview text was subjected to qualitative thematic content analysis. RESULTS: Analysis revealed the following three categories: (1) feeling scared and uncared for during acute situations; (2) appreciating the opportunity to participate in care and becoming a family; and (3) needing continued care. Based on these three categories, a recurring theme was identified: struggling to be recognized by care staff as a partner in the family was revealed. CONCLUSION: Although fathers lack support and understanding from care staff, they strive to fulfill their roles as fathers by guarding their families and keeping them together. Caregivers involved in the childbirth process should realize that by acknowledging and encouraging fathers in these roles, they in turn support the entire family unit. Interventions developed for fathers and family care requires further development. Additional research concerning how midwives and critical care nurses (CCNs) view the presence of fathers in the emergency situations that may accompany childbirth is also needed. PMID- 24216045 TI - The influence of breastfeeding beliefs on the sexual behavior of the Tarok in north-central Nigeria. AB - OBJECTIVE: The paper investigated some of the beliefs around the breastfeeding norm of the postpartum abstinence and how these influence sexual behavior. It was based on a larger project which explored how gender relations affect reproductive processes and the reproductive health of Tarok women in north-central Nigeria. METHODS: Research was conducted in four Tarok communities using qualitative instruments, namely in-depth interviews (IDIs) and focus group discussion (FGD) guides. Participants were female and male community members of 15 years and above. Sixteen IDIs (four per community) were conducted with women, religious and traditional leaders as well as senior health providers. Twenty-four FGD sessions (six per community) were held with different groups in the community and data were descriptively analyzed. RESULTS: Findings demonstrated customary double standards in sexual matters; the significance and influence of certain unfounded traditional beliefs around breastfeeding on sexual behavior and choices; as well as some of the changes that characterize sexual relationships among modern Tarok couples brought about by Christianity, Western education and modernity. CONCLUSION: Traditional breastfeeding norms and beliefs seek to overly control women's sexuality while giving precedence to the interest of the child and its father. The study calls for a change in attitude to meet the demands of the current reality in order to strengthen marital unions and guarantee healthy families. PMID- 24216046 TI - Reference chart of inspiratory muscle strength: a new tool to monitor the effect of pre-operative training. AB - OBJECTIVES: To develop a reference chart to monitor inspiratory muscle strength during pre-operative inspiratory muscle training for patients at high risk of developing postoperative pulmonary complications awaiting coronary artery bypass graft (CABG) surgery. DESIGN: Secondary data analysis using patients from the intervention arm of a randomised clinical trial. SETTING: University medical centre. PARTICIPANTS: Patients at high risk of developing postoperative pulmonary complications awaiting CABG surgery. INTERVENTIONS: Patients performed inspiratory muscle training seven times per week for at least 2 weeks before surgery. MAIN OUTCOME MEASURES: Maximal inspiratory muscle strength. RESULTS: A new reference chart was produced using a non-linear time trend model with a normal error structure. CONCLUSIONS: The chart is a novel tool for monitoring the progress of inspiratory muscle training for physiotherapy practice. Wider use of this chart is recommended. PMID- 24216048 TI - Monoclonal antibody-based immunotherapy of ovarian cancer: targeting ovarian cancer cells with the B7-H3-specific mAb 376.96. AB - OBJECTIVE: The high rate of relapse in patients with advanced ovarian cancer likely reflects the chemoresistance of cancer initiating cells (CICs). We evaluated the anti-tumor activity of monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian carcinoma cells (OCCs), in combination with the tyrosine kinase inhibitor Sunitinib and chemotherapy on chemosensitive and chemoresistant cells and CICs. METHODS: Eight ovarian cancer cell lines including platinum- and taxane-resistant cell lines were analyzed by flow cytometry to establish expression of the mAb 376.96-defined-B7-H3-epitope on differentiated ovarian cancer cells and CICs. Samples from 10 ovarian cancer patients were analyzed via immunohistochemistry for mAb 376.96-defined-B7-H3 epitope expression. In vitro studies assessed mAb 376.96 alone and in combination with Sunitinib on the growth of chemosensitive and chemoresistant cell lines and on the content of CICs. RESULTS: The mAb-376.96-defined-B7-H3 epitope is expressed on both differentiated cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines and 10 patient derived ovarian cancer tumors. In vitro treatment of chemoresistant cell lines with mAb 376.96 resulted in decreased cell viability. mAb 376.96 enhanced the cytotoxicity of Sunitinib and reduced the content of CICs. CONCLUSION: The mAb-376.96-defined-B7-H3-epitope was found to be expressed on both differentiated ovarian cancer cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines. mAb 376.96 inhibited the in vitro growth of chemosensitive and chemoresistant OCCs and reduced the content of CICs when used with Sunitinib. Further studies examining B7-H3 as a potential target of mAb-based immunotherapy for this type of malignancy are warranted. PMID- 24216049 TI - Modified gluteal fold advancement V-Y flap for vulvar reconstruction after surgery for vulvar malignancies. AB - OBJECTIVE: The aim of the study is to assess the feasibility and complications of the modified V-Y advancement gluteal flap in the vulvo-perineal reconstruction among women operated for vulvar malignancies. METHODS: From December 2008 to April 2012 women who underwent radical surgery for invasive vulvar cancer were considered for the study. Patients after demolitive procedure were submitted to reconstructive step (Group A) consisting of bilateral or monolateral V-Y advancement fascio-cutaneous flap, from gluteal fold. Surgical results were compared to those of a historical group of patients (Group B) with the same characteristics but not submitted to the reconstructive step. RESULTS: Twenty nine patients were considered for the study and submitted to radical surgery followed by V-Y flap. Surgical results were compared to those of 78 patients submitted to demolitive surgery only. There were no differences in terms of clinical characteristics between the two groups. The average length of hospital stay was 7 and 10 days, respectively for Groups A and B (P=0.0067). Mean operating time was higher in Group A, 210 vs 120 min (P<0.00001). Among women with tumor size larger than 4 cm (27 Group A, 30 Group B), Group A had lower complication rate (dehiscence 11% vs 40%; P=0.0172). CONCLUSIONS: Modified gluteal fold advancement V-Y flap is a safe and simple procedure and can be harvested in a single surgery session. It could be able to reduce hospital stay and in patients with large loss of substance could reduce rate of complications. PMID- 24216050 TI - Geranylated 2-arylbenzofurans from Morus alba var. tatarica and their alpha glucosidase and protein tyrosine phosphatase 1B inhibitory activities. AB - Ten new geranylated 2-arylbenzofuran derivatives, including two monoterpenoid 2 arylbenzofurans (1 and 2), two geranylated 2-arylbenzofuran enantiomers (3a and 3b), and six geranylated 2-arylbenzofurans (4-9), along with four known 2 arylbenzofurans (10-13) were isolated from the root bark of Morus alba var. tatarica. Their structures and relative configurations were established on the basis of spectroscopic data analysis. Compounds 3-7 with one asymmetric carbon at C-7" were supposed to be enantiomeric mixtures confirmed by chiral HPLC analysis, and the absolute configurations of each enantiomer in 3-7 were determined by Rh2(OCOCF3)4-induced CD and Snatzke's method. The enantiomers with the substituting group at C-2' exhibited better resolutions on a Chiralpak AD-H column than those with the substituting group at C-4'. Compounds 1-7, 10, 11 and 13, showed alpha-glucosidase inhibitory activities with IC50 values of 11.9-131.9 MUM, and compounds 1 and 9-13 inhibited protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 7.9-38.1 MUM. PMID- 24216051 TI - Cycloartane glycosides from Astragalus plumosus var. krugianus and evaluation of their antioxidant potential. AB - The methanol extracts of Astragalus plumosus var. krugianus Chamb. & Matthews afforded sixteen cycloartane glycosides among which krugianoside A, was never reported before. All compounds were evaluated for their cytotoxic activity in human skin fibroblast WS1 cells. For compounds exhibiting no significant effect on WS1 viability, the antioxidant potential was examined. Compounds 1 and 8 prevented elevation of ROS induced by t-BOOH, suggesting the potential activity of these compounds to protect fibroblasts from oxidative stress. PMID- 24216052 TI - [How to improve supervision of carbapenem's prescriptions? Development of a cross disciplinary computerized system]. PMID- 24216053 TI - Successful cardiac resynchronisation therapy in Duchenne muscular dystrophy: a 5 year follow-up. PMID- 24216054 TI - [Letter on the article: "senile systemic amyloidosis: definition, diagnosis, why thinking about?"]. PMID- 24216055 TI - Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs. AB - Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1 8MUg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension. PMID- 24216056 TI - Examining associations between anxiety and cortisol in high functioning male children with autism. AB - BACKGROUND: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal. METHODS: Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol). RESULTS: Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism. CONCLUSIONS: Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances. PMID- 24216057 TI - Osteoarthritis bone marrow lesions at the knee and large artery characteristics. AB - OBJECTIVE: There is evidence to suggest vascular involvement in the initiation and progression of osteoarthritis (OA). The relationship between large artery characteristics and pathogenesis of OA has not been investigated and was the aim of this study. DESIGN: Large artery characteristics (i.e., aortic stiffness, brachial and central blood pressure (BP) variables) and bone marrow lesions (BMLs; measured by magnetic resonance imaging as a surrogate index of OA) were recorded in 208 participants (aged 63 +/- 7 years; mean +/- SD) with symptomatic knee OA. Relationships between large artery characteristics and BML were assessed by multiple regression adjusting for age, sex and body mass index. RESULTS: There was a high prevalence of BML presence in the study population (70%), but no significant difference between participants with and without BML for all large artery and BP variables (P > 0.05 all). Furthermore, there were no significant relationships between BML size and aortic stiffness (r = -0.033, P = 0.71), central pulse pressure (r = 0.028, P = 0.74), augmentation index (r = 0.125, P = 0.14), brachial pulse pressure (r = 0.005, P = 0.95) or brachial systolic BP (r = -0.066, P = 0.44). When participants were stratified according to high or low aortic stiffness, there was no significant difference between groups regarding the proportion of those with a BML (64% vs. 70% respectively; P = 0.69). CONCLUSIONS: Variables indicative of large artery characteristics are not significantly correlated with BML size or presence in people with symptomatic knee OA. Thus, large artery characteristics may not have a causative influence in the development of OA, but this needs to be confirmed in prospective studies. PMID- 24216058 TI - Osteoarthritis--a case for personalized health care? AB - For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular relevance, due to the heterogeneity of the disease and the very large number of affected individuals. There is a need to pair the right patients with the right therapeutic modes of action. At present, the clinical trial failures in OA may be a consequence of both bona fide treatment failures and trial failures due to clinical design deficiencies. Tools are needed for characterization and segregation of patients with OA. Key lessons may be learned from advances with another form of arthritis, namely rheumatoid arthritis (RA). Personalized health care (PHC) may be more advantageous for a number of specific indications which are characterized by costly therapy, low response rates and significant problems associated with trial and error prescription, including the risk of serious side effects. We discuss the use of diagnostic practices guiding RA treatment, which may serve as a source of key insights for diagnostic practices in OA. We discuss the emerging concept of PHC, and outline the opportunities and current successes and failures across the RA field, as the OA field collects further data to support the hypothesis. We attempt to outline a possible path forward to assist patients, physicians, payers and the pharmaceutical industry in assuring the 'right' patients are treated with the 'right drug' in OA. Finally we highlight methods for possible segregation of OA patients that would allow identification of patient subtypes, such as OA driven by inflammation that may be ideally suited for PHC and for targeted therapies. PMID- 24216059 TI - Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. AB - OBJECTIVES: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren Lawrence (KL) score. METHODS: hsCRP, CRPM and MMP-degraded type I, II and III collagen (type I collagen degraded by MMP (C1M), type II collagen degraded by MMP (C2M) and type III collagen degraded by MMP (C3M)) were quantified by enzyme linked immunosorbent assays (ELISA) in serum of 342 patients with symptomatic knee OA of which 60 underwent total knee replacement (TKR). KL was obtained. Patients were divided into quartiles by hsCRP and CRPM levels, where Q1 and Q4 were low or high in both. The biomarker levels of healthy adults provided in the ELISA kits were used as reference level. RESULTS: hsCRP was elevated in TKR (5.9(3.6-8.2 95% confidence interval (CI)) MUg/mL) compared to reference level (3 MUg/mL), while CRPM was highly elevated with OA independent of KL (10-14 ng/mL) compared to reference level (5 ng/mL). Q4 had higher KL than Q1 (P < 0.001), Q2 (P = 0.017) and Q3 (P < 0.001). C1M, C2M and C3M were lowest in Q1. C1M was elevated in Q3 compared to Q2 (P < 0.001), whereas C3M was lower (P = 0.019). CONCLUSION: A bigger proportion of patients were elevated in CRPM compared to hsCRP, indicating MMP-derived inflammation as a component of OA. Moreover, the levels of MMP-degraded collagens differed between the subgroups segregated by inflammation, indicating distinctively different subpopulation selected by inflammation. PMID- 24216060 TI - Measurement properties of performance-based outcome measures to assess physical function in young and middle-aged people known to be at high risk of hip and/or knee osteoarthritis: a systematic review. AB - OBJECTIVES: To systematically appraise the evidence on measurement properties of performance-based outcome measures to assess physical function in young and middle-aged people known to be at high risk of hip and/or knee osteoarthritis (OA). METHODS: Electronic searches were performed in MEDLINE, CINAHL, Scopus and SPORTDiscus in May 2013. Two reviewers independently rated the measurement properties using the 4-point COSMIN checklist. Best evidence synthesis was made using COSMIN quality, consistency and direction of findings and sample size. RESULTS: Twenty of 2736 papers were eligible for inclusion and 24 different performance-based outcome measures knee or obese populations were evaluated. No tests related to hip populations were included. Twenty-five measurement properties including reliability (nine studies), construct validity (hypothesis testing) (nine studies), measurement error (three studies), structural validity (two studies), interpretability (one study) and responsiveness (one study) were evaluated. A positive rating was given to 12.5% (30/240) of all possible measurement ratings. Tests were grouped into two categories based on the population characteristics. The one-legged hop for distance, followed by the 6-m timed hop and cross over hop for distance were the best-rated tests for the knee injured population. Whereas the 6-min walk test was the only included test for the obese population. CONCLUSION: This review highlights the many gaps in knowledge about the measurement properties of performance-based outcome measures for young and middle-aged people known to be at high risk of hip and/or knee OA. There is a need for consensus on which outcome measures should be used and/or combined when assessing physical function in this population. Further good quality research is required. PMID- 24216061 TI - Trabecular bone texture detected by plain radiography is associated with an increased risk of knee replacement in patients with osteoarthritis: a 6 year prospective follow up study. AB - OBJECTIVE: To examine the association between trabecular bone texture and knee joint replacement (KJR) measured using a variance orientation transform (VOT) method. METHODS: The association of trabecular bone texture and KJR was examined prospectively over 6 years in 123 subjects with symptomatic knee osteoarthritis (OA): data regarding KJR was available for 114 (93%). At baseline, weight-bearing anteroposterior tibio-femoral radiographs were acquired. Trabecular bone texture regions were selected from the medial and lateral subchondral tibia. The VOT method was applied to each region and five fractal bone texture parameters, i.e., mean fractal dimension (FDMEAN), fractal dimensions in the horizontal (FDH) and vertical (FDV) directions, and along the roughest part of trabecular bone (FD(Sta)), and texture aspect ratio (Str) were calculated. The association between groups with increasing baseline fractal parameters (defined using tertiles) with risk of JR was examined using logistic regression. RESULTS: 28 (25%) participants' study knees underwent KJR over 6 years. Participants with KJR had lower medial FD(MEAN) and FD(H) parameters (P = 0.02 for difference). With increasing FD(MEAN), adjusted for age, gender, body mass index (BMI), osteophyte grade, joint space narrowing (JSN) grade and WOMAC pain score, the odds of KJR was reduced (P = 0.04 for trend). CONCLUSION: This study suggests that the texture of medial tibial trabecular bone measured from plain radiographs is related to the risk of KJR: with increasing FD(MEAN) (the overall measure of bone texture roughness) the risk of KJR was reduced, independent of other clinical predictors of joint replacement. Tibial trabecular bone texture may be a useful marker of disease progression and a target of therapy in OA. PMID- 24216062 TI - Dynamical structure of the short multifunctional peptide BP100 in membranes. AB - BP100 is a multifunctional membrane-active peptide of only 11 amino acids, with a high antimicrobial activity, an efficient cell-penetrating ability, and low hemolytic side-effects. It forms an amphiphilic alpha-helix, similar to other antimicrobial peptides like magainin. However, BP100 is very short and thus unlikely to form membrane-spanning pores as proposed for longer peptides as a mechanism of action. We thus studied the conformation, membrane alignment and dynamical behavior of BP100 in lipid bilayers (DMPC/DMPG), using oriented circular dichroism (OCD) and solid-state (19)F and (15)N NMR. According to OCD and (15)N NMR, the BP100 helix is oriented roughly parallel to the membrane surface, but these methods yield no information on the azimuthal alignment angle or the dynamics of the molecule. To address these questions, a systematic (19)F NMR analysis was performed, which was not straightforward for this short peptide. Only a limited number of positions could be (19)F-labeled, all of which are located on one face of the helix, which was found to lead to artifacts in the data analysis. It was nevertheless possible to reconcile the (19)F NMR data with the OCD and (15)N NMR data by using an advanced dynamical model, in which peptide mobility is described by fluctuating tilt and azimuthal angles with Gaussian distributions. (19)F NMR thus confirmed the regular alpha-helical conformation of BP100, revealed its azimuthal angle, and described its high mobility in the membrane. Furthermore, the very sensitive (19)F NMR experiments showed that the alignment of BP100 does not vary with peptide concentration over a peptide-to lipid molar ratio from 1:10 to 1:3000. PMID- 24216063 TI - Neuropsychological outcomes of stereotactic radiotherapy for cerebral arteriovenous malformations. AB - To our knowledge, this is the first study to investigate cognitive outcome in patients with large or surgically inaccessible cerebral arteriovenous malformations (AVMs), who were treated with hypo-fractionated stereotactic radiotherapy (HSRT). A sample of 10 patients with AVMs was assessed up to 3.5 years post-HSRT. All patients were treated with HSRT to a total dose of 55 Gy in 11 fractions over a treatment period of 2.5 weeks. Neuropsychological assessments were given prior to radiotherapy and then at three time points following radiotherapy: 6 weeks, 6 months and 2.5-3.5 years post-treatment. The cognitive domains of attention, processing speed, learning, memory, semantic processing, naming, verbal fluency, visuospatial and executive function were assessed. Findings revealed that prior to radiotherapy the patient group was impaired in five of the nine cognitive domains. Post-treatment performances remained stable in the majority of domains; however, there was some fluctuation in semantic processing and memory performances. At 6 weeks post-treatment, a mild decrement was found in semantic processing ability; however, restoration to baseline levels was observed from 6 months onwards. At 2.5-3.5 years post-treatment, improvement was seen in the cohort's ability to remember new information when performances were compared with earlier time points. This study demonstrated improvements in memory several years after HSRT treatment. Further, this form of treatment was not associated with long-term, harmful cognitive side effects for these 10 patients encouraging further study of this treatment method. Further evaluation of the entire cohort is required to assess efficacy in terms of AVM obliteration and other potential side effects. PMID- 24216064 TI - Predictive value of the Royal Melbourne Hospital Falls Risk Assessment Tool (RMH FRAT) for post-stroke patients. AB - Falls after stroke are common and carry a significant disease burden. Several scores aim to identify patients who are at risk of falls to implement primary prevention therapy. The aim of this study was to determine the validity of the commonly used Falls Risk Assessment Tool (FRAT) developed at the Royal Melbourne Hospital (RMH) in 1995 for predicting falls after a stroke. The RMH FRAT was administered within 2 weeks after discharge post-stroke. Occurrence of falls was recorded at 3 and 6 months post-stroke in 202 and 152 patients, respectively. In our study 90% of patients were placed in the RMH FRAT high risk or medium risk group. In these two groups the RMH FRAT did not provide sufficient predictive value. PMID- 24216065 TI - Effects of the osmolyte TMAO (Trimethylamine-N-oxide) on aqueous hydrophobic contact-pair interactions. AB - Osmolytes are small, soluble organic molecules produced by living organisms for maintaining cell volume. These molecules have also been shown to have significant effects on the stability of proteins. Perhaps one of the most studied osmolytes is Trimethylamine-N-oxide (TMAO). Thermodynamic studies of the effects of TMAO on proteins have shown that this molecule is a strong stabilizer of the protein folded state, thus being able to counteract the effects of protein denaturants such as urea and guanidine hydrochloride. Most studies of TMAO effects on bio molecular stability have until now been focused on how the osmolyte reduces the solubility of polypeptide backbones, while the effects of TMAO on hydrophobic interactions are still not well understood. In fact, there are few experimental data measuring the effect of TMAO on hydrophobic interactions. This work studies phenyl and alkyl contact pairs as model hydrophobic contact pairs. The formation of these contact pairs is monitored using fluorescence, i.e., through the quenching of phenol fluorescence by carboxylate ions; and a methodology is developed to isolate hydrophobic contributions from other interactions. The data demonstrate that the addition of TMAO to the aqueous solvent destabilizes hydrophobic contact pairs formed between alkyl and phenyl moieties. In other words, TMAO acts as a "denaturant" for hydrophobic interactions. PMID- 24216066 TI - Releasing polysaccharide and protein from yeast cells by ultrasound: selectivity and effects of processing parameters. AB - A 20 kHz high-intensity ultrasound was employed for the selective release of polysaccharide and protein from yeast cells. While the release of polysaccharide and protein was affected by most of the processing parameters, the release selectivity, which is the ratio of the amount of polysaccharide released to that of protein, designated as T/P value, was only influenced by sonication time, temperature and ionic strength, among which temperature had the greatest influence. The T/P value at 85 degrees C was a factor of 9.3 of the one at 25 degrees C. The underlying mechanism of this selectivity is speculated to be thermal denaturation and aggregation of protein within yeast cells at elevated temperatures leading to the decrease of protein release by ultrasound. This finding may be useful in exploring a novel selective process for producing polysaccharide and protein fractions from yeast biomass. PMID- 24216067 TI - Stabilizing in vitro ultrasound-mediated gene transfection by regulating cavitation. AB - It is well known that acoustic cavitation can facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, partially due to the unstationary behavior of the initiation and leveling of cavitation, the sonoporation effect is usually unstable, especially in low intensity conditions. A system which is able to regulate the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop is implemented and its effect on in vitro gene transfection is tested. The regulated system provided better time stability and reproducibility of the cavitation levels than the unregulated conditions. Cultured hepatoma cells (BNL) mixed with 10 MUg luciferase plasmids are exposed to 1-MHz pulsed ultrasound with or without cavitation regulation, and the gene transfection efficiency and cell viability are subsequently assessed. Experimental results show that for all exposure intensities (low, medium, and high), stable and intensity dependent, although not higher, gene expression could be achieved in the regulated cavitation system than the unregulated conditions. The cavitation regulation system provides a better control of cavitation and its bioeffect which are crucial important for clinical applications of ultrasound-mediated gene transfection. PMID- 24216068 TI - Sample preparation for combined chemical analysis and in vitro bioassay application in water quality assessment. AB - The combination of in vitro bioassays and chemical screening can provide a powerful toolbox to determine biologically relevant compounds in water extracts. In this study, a sample preparation method is evaluated for the suitability for both chemical analysis and in vitro bioassays. A set of 39 chemicals were spiked to surface water, which were extracted using Oasis MCX cartridges. The extracts were chemically analyzed by liquid chromatography linear ion trap Orbitrap analysis and recoveries appeared to be on average 61% Compounds with logK(ow) values in the range between 0 and 4 are recovered well using this method. In a next step, the same extracts were tested for genotoxic activity using the Comet assay and Ames fluctuation test and for specific endocrine receptor activation using a panel of CALUX assays, for estrogenic (ER), androgenic (AR), glucocorticoid (GR), progestagenic (PR), and thyroidogenic (TR) agonistic activities. The results of the genotoxicity assays indicated that spiked genotoxic compounds were preserved during sample preparation. The measured responses of the GR CALUX and ER CALUX assays were similar to the predicted responses. The measured responses in the AR CALUX and PR CALUX assays were much lower than expected from the analytical concentration, probably due to antagonistic effects of some spiked compounds. Overall, the presented sample preparation method seems to be suitable for both chemical analysis and specific in vitro bioassay applications. PMID- 24216069 TI - Effects of omega-3 polyunsaturated fatty acid supplementation in patients with chronic chagasic cardiomyopathy: study protocol for a randomized controlled trial. AB - BACKGROUND: Chronic chagasic cardiomyopathy is an inflammatory disease that occurs in approximately 30% of patients infected by the protozoan Trypanosoma cruzi, and it has a profile of high morbidity and mortality. The worst prognosis and the progression of this cardiomyopathy are associated with an exacerbated immune response and the production of proinflammatory cytokines, which also occur in other cardiomyopathies. Some nutrients, including omega-3 polyunsaturated fatty acids (PUFAs), promote the inhibition and/or stimulation of cytokine production. The objective of this trial is to study the effects of omega-3 PUFA supplementation on the inflammatory response and lipid profile in patients with chronic chagasic cardiomyopathy. METHODS/DESIGN: This is a parallel, randomized, placebo-controlled, double-blind clinical trial with 40 patients that will be conducted at a reference unit for Chagas disease patients, where the patients will be selected. The study will include patients with chronic chagasic cardiomyopathy who are 18 years of age or older. The exclusion criteria are (a) ongoing diarrheal disease, (b) inflammatory bowel disease, (c) diabetes or other endocrine disease, (d) use of fibrates, niacin, or statins, (e) use of anti inflammatory drugs, (f) pregnant and lactating women, (g) use of vitamin, mineral, or omega-3 supplementation during the previous 30 days, (h) hospital admission during the study, and (i) other associated cardiomyopathies. The intervention will be treatment with omega-3 PUFAs at a dose of 3 g/day for 8 weeks, compared to placebo (corn oil). The primary endpoints will be the concentrations of inflammatory markers (interleukin (IL)-1, IL-2, IL-4, IL-6, IL 10, tumor necrosis factor (TNF)alpha, interferon (IFN)gamma, and transforming growth factor (TGF)beta). Secondary endpoints will be the fasting glucose, lipid, and anthropometric profiles. For statistical analysis, we plan to run either a t test or Wilcoxon test (numerical variables) and Pearson's chi2 or Fisher's exact test (categorical data), as appropriate. DISCUSSION: Evidence suggests that the anti-inflammatory action of omega-3 PUFAs may have beneficial effects on chronic chagasic cardiomyopathy, as shown for other cardiomyopathies, due to improved control of the inflammatory response. At the end of the study, we predict that patients will have lower inflammatory markers and an improved metabolic and anthropometric profile. TRIAL REGISTRATION: Current Controlled Trials NCT01863576. PMID- 24216070 TI - Parents' first concerns about toddlers with autism spectrum disorder: effect of sibling status. AB - Symptoms of autism spectrum disorders may appear as early as 6 months, but parent concern, which can precipitate evaluation, often lags significantly. The presence of typical or atypical older siblings can change parents' sensitivity to departures from typical development. This study investigated type and age of parent's first concerns in toddlers with autism spectrum disorder, prior to diagnosis. Participants had (1) at least one older sibling with autism spectrum disorder (Sibs-ASD); (2) only typically developing older siblings (Sibs-TD), or (3) were only/oldest (No-Sibs). Specific autism spectrum disorder diagnoses and symptom severity were similar among groups. Developmentally, No-Sibs showed the largest delays, followed by Sibs-TD, followed by Sibs-ASD. Mean age of first concern was 16 months for No-Sibs, 14 months for Sibs-TD, and 10 months for Sibs ASD. Age of first concern differed significantly by group, even after controlling for mother's age and education. Concern about language was prevalent in all groups. Thus, the presence of an older child with typical or, especially, atypical development was associated with earlier concerns for the affected child, despite milder developmental delays. These findings underscore the importance of encouraging parents to report concerns to pediatricians, routine standardized screening for autism spectrum disorder, and the need for pediatrician vigilance, especially for only or oldest children. PMID- 24216071 TI - Post-traumatic growth in mothers of children with autism: a phenomenological study. AB - While the adverse effects of raising a child with autism are well demonstrated, there have been few reports of the post-traumatic growth of mothers of children with autism. The purpose of this research was to explore dimensions of post traumatic growth in this population in Mainland China and identify the factors facilitating post-traumatic growth. A total of 11 mothers of pre-school children were recruited from five rehabilitation centres of children with disabilities in Shanghai. The semi-structured interviews were conducted between August 2012 and October 2012 and analysed using thematic analysis. The data partially confirmed Tedeschi and Calhoun's model of post-traumatic growth. A new philosophy of life, appreciation of life, relating to others, personal strength and spiritual change were five domains of post-traumatic growth in mothers of children with autism. Perceived social support, peer example, effective coping style and self-efficacy enhancement were facilitating factors of post-traumatic growth. Further studies are needed to understand how to promote the post-traumatic growth of mothers of children with autism. PMID- 24216075 TI - Evaluation of apoptosis in long-term culture of vitrified mouse whole ovaries. AB - The purpose of the present study was to investigate the development of follicles and incidence of apoptosis in vitrified neonatal mouse ovaries cultured in vitro in the presence of leukemia inhibitory factor (LIF). The vitrified and non vitrified ovaries of 1-week-old mouse were cultured in the presence or absence of LIF for 7 days. At the beginning and at the end of culture period in each ovary of all groups of study the mean area and the development of ovarian follicles were analyzed; moreover, the incidence of apoptosis was assessed by transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method, DNA laddering and caspase-3/7 activity technique. The hormonal assay was done on the conditioned media collected during culture period. The proportion of preantral follicles and the levels of hormones increased in all cultured groups and it was significantly higher in LIF treated groups than in their control (P<0.001). The ultrastructural characteristics of cell death, DNA fragmentation and TUNEL positive signals were prominent in vitrified cultured ovaries. The level of caspase-3/7 activity was higher in vitrified cultured ovaries. LIF supplementation during 7 days of culture appeared to significantly preserve cells function and increase the follicular development of both vitrified and non-vitrified ovaries. PMID- 24216076 TI - Improving communication between health-care professionals and patients with limited English proficiency in the general practice setting. AB - Quality service provision and patient safety and satisfaction in encounters with health-care professionals relies on effective communication between the practitioner and patient. This study aimed to identify effective practices for improving communication between clinical staff in general practice and patients with limited English proficiency, and to promote their implementation in general practice. Effective interventions and strategies were identified from a review of international research. Experiences with their use in practice were explored via focus group discussions with general practitioners and practice nurses. The results suggest that, wherever possible, communication in the patient's primary language is preferable; use of a qualified medical interpreter should be promoted, and practices should have a standardised and documented procedure for accessing interpreter services. General practice staff must increase their awareness about services that are available to facilitate communication with patients with limited English proficiency, and also develop attitudes, both individual and organisational, that will maximise the effectiveness of these strategies. These findings were used to develop brief, evidence-based practice guidelines that were disseminated to focus group participants for evaluation of utility and general feedback. This evidence-based guidance is now available to assist clinical and administrative general practice staff across regional and metropolitan South Australia. PMID- 24216077 TI - Management of lung nodules in 2013. PMID- 24216078 TI - Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization. AB - The statistical identifiability of nonlinear pharmacokinetic (PK) models with the Michaelis-Menten (MM) kinetic equation is considered using a global optimization approach, which is particle swarm optimization (PSO). If a model is statistically non-identifiable, the conventional derivative-based estimation approach is often terminated earlier without converging, due to the singularity. To circumvent this difficulty, we develop a derivative-free global optimization algorithm by combining PSO with a derivative-free local optimization algorithm to improve the rate of convergence of PSO. We further propose an efficient approach to not only checking the convergence of estimation but also detecting the identifiability of nonlinear PK models. PK simulation studies demonstrate that the convergence and identifiability of the PK model can be detected efficiently through the proposed approach. The proposed approach is then applied to clinical PK data along with a two-compartmental model. PMID- 24216079 TI - Equity, socioeconomic inequalities and cardiovascular disease. PMID- 24216080 TI - Anemia and iron deficiency in heart failure. AB - Heart failure is a common problem and a major cause of mortality, morbidity and impaired quality of life. Anemia is a frequent comorbidity in heart failure and further worsens prognosis and disability. Regardless of anemia status, iron deficiency is a common and usually unidentified problem in patients with heart failure. This article reviews the mechanisms, impact on outcomes and treatment of anemia and iron deficiency in patients with heart failure. PMID- 24216081 TI - Early handling effect on female rat spatial and non-spatial learning and memory. AB - This study aims at providing an insight into early handling procedures on learning and memory performance in adult female rats. Early handling procedures were started on post-natal day 2 until 21, and consisted in 15 min, daily separations of the dams from their litters. Assessment of declarative memory was carried out in the novel-object recognition task; spatial learning, reference- and working memory were evaluated in the Morris water maze (MWM). Our results indicate that early handling induced an enhancement in: (1) declarative memory, in the object recognition task, both at 1h and 24h intervals; (2) reference memory in the probe test and working memory and behavioral flexibility in the "single-trial and four-trial place learning paradigm" of the MWM. Short-term separation by increasing maternal care causes a dampening in HPA axis response in the pups. A modulated activation of the stress response may help to protect brain structures, involved in cognitive function. In conclusion, this study shows the long-term effects of a brief maternal separation in enhancing object recognition , spatial reference- and working memory in female rats, remarking the impact of early environmental experiences and the consequent maternal care on the behavioral adaptive mechanisms in adulthood. PMID- 24216082 TI - Sleep duration is affected by social relationships among sleeping partners in wild Japanese macaques. AB - Co-sleeping behaviour, such as sharing a sleeping site or bed, should play an important role in determining sleep structure in mammals by mitigating predation pressure and harsh abiotic conditions during sleep. Although environmental factors surrounding sleeping sites have been studied, there is very little information on the effects of the social environment within the site on sleep in animals other than humans. Here, we quantified the duration of nighttime sleep of wild primates during behavioural observations. Wild Japanese macaques (Macaca fuscata yakui) form clusters at sleeping sites, where they huddle with group members. Macaques slept for longer when huddled in sleeping clusters with natal members than in those with non-natal members. A high degree of synchronisation of wakefulness in pairs of macaques huddling in non-natal clusters suggested that their sleep was often interrupted by the wakefulness of huddling members at night. Our results suggest that familiarity and closeness to huddling partners influence sleep duration. PMID- 24216083 TI - Selfish mothers? An empirical test of parent-offspring conflict over extended parental care. AB - Parent-offspring conflict (POC) theory is an interesting conceptual framework for understanding the dynamics of parental care. However, this theory is not easy to test empirically, as exact measures of parental investment in an experimental set up are difficult to obtain. We have used free-ranging dogs Canis familiaris in India, to study POC in the context of extended parental care. We observed females and their pups in their natural habitat for the mother's tendency to share food given by humans with her pups in the weaning and post-weaning stages. Since these dogs are scavengers, and depend largely on human provided food for their sustenance, voluntary sharing of food by the mother with her pups is a good surrogate for extended parental care. Our behavioural observations convincingly demonstrate an increase of conflict and decrease of cooperation by the mother with her offspring over given food within a span of 4-6 weeks. We also demonstrate that the competition among the pups in a litter scales with litter size, an indicator of sib-sib competition. PMID- 24216084 TI - Cultural Validation of the Turkish Version of the Infertility Self-Efficacy Scale Short Form (TISE-SF). AB - PURPOSE: To translate and test the psychometric properties of the Turkish version of the Infertility Self-Efficacy Scale-Short Form (TISE-SF). METHODS: The convenience sample consisted of 120 infertile women. A psychometric research design was used with content and construct validity and reliability. RESULTS: Cronbach's alpha of .78 showed moderate reliability, whereas item-total correlations ranged from .30 to .54. Factor analysis extracted a single component, explaining 40.3% of the variance. Kendall W showed agreement with each expert regarding the appropriateness of the items, confirming the content validity of the translated TISE-SF. CONCLUSION: The results supported the construct validity and reliability of the TISE-SF for measuring infertility self efficacy in a population of Turkish women. IMPLICATIONS: Evaluating infertile women's perception of self-efficacy with the TISE-SF may be useful in clinical studies in Turkey. TISE-SF can be used by professionals as a counseling tool to help guide women in managing their treatments at infertility centers. PMID- 24216085 TI - Nursing Students in a Global Learning Environment: Creative Teaching Methods on Culture, Emotion, and Communication. AB - PURPOSE: Two tools were created to help international students to better understand culture by becoming more astute observers of nonverbal behaviors, particularly behaviors depicting emotions among Norwegian students. DESIGN/METHOD: The two tools were a trilingual list of words illustrating emotions and an exercise with images to practice verbalizing their observations of emotional expression. FINDINGS: Students compared the subdued behaviors of Norwegians to the Israelis' very vivid behaviors. The intense emotional expression of Israelis influenced their interpretations. By making comparisons and through the experiences with Israelis, they learned more about culture and their own emotional expression. DISCUSSIONS AND CONCLUSIONS: Creative strategies can contribute to students understanding and reflection of patients in a different culture. IMPLICATIONS FOR PRACTICE: Encouraging students to grasp the nuances of emotional expression is part of understanding a different culture. Students, like faculty, learn that self-exploration is an evolving process that requires checking out one's assumptions and interpretations. PMID- 24216086 TI - Effects of polysaccharides from Pholiota nameko on maturation of murine bone marrow-derived dendritic cells. AB - This paper studied some structure characters of the Pholiota nameko polysaccharides (PNPS-1), including morphology under SEM and AFM, also the effects of PNPS-1 on the maturation of bone marrow dendritic cells (BMDCs) via concrete changes both inside and outside BMDCs. These impacts on BMDCs were assessed with use of inverted phase contrast microscope for morphology, flow cytometry for key surface molecules, mixed lymphocyte reaction (MLR) for allogeneic T cells proliferation, and bio-assay and enzyme linked immunosorbent assay (ELISA) for cytokine production. We found that PNPS-1 could inhibit phenotypic maturation as evidenced by decreasing expression of CD11c, CD40, CD80, CD83, CD86, and I-A/I-E. Functional maturation inhibition was further confirmed by decreased naive T cell stimulatory activity of BMDCs. Finally, PNPS-1 also stimulated production of more cytokine IL-10 and less IL-12 and TNF-alpha. These data indicated that PNPS-1 could markedly inhibit the maturation of BMDCs and had potential significant down-regulation immunity. PMID- 24216087 TI - DNA modifications repaired by base excision repair are epigenetic. AB - CREB controls ~25% of the mammalian transcriptome. Small changes in binding to its consensus (CRE) sequence are likely to be amplified many fold in initiating transcription. Here we show that DNA lesions repaired by the base excision repair (BER) pathway modulate CREB binding to CRE. We generated Kd values by electrophoretic mobility shift assays using purified human CREB and a 39-mer double-stranded oligonucleotide containing modified or wild-type CRE. CRE contains two guanine residues per strand, one in a CpG islet. Alterations in CRE resulted in positive or negative changes in Kd over two orders of magnitude depending on location and modification. Cytosine methylation or oxidation of both guanines greatly diminished binding; a G/U mispair in the CpG context enhanced binding. Intermediates in the BER pathway at one G residue or the other resulted in reduced binding, depending on the specific location, while there was no change in binding when the single G residue outside of the CpG islet was oxidized. CREB recruits other partners after dimers form on DNA. Only UpG increased DNA.CREB dimer formation. Since oxidation is ongoing and conversion of cytosine to uracil occurs spontaneously or at specific times during differentiation and development, we propose that BER substrates are epigenetic and modulate transcription factor recognition/binding. PMID- 24216088 TI - Dopa-decarboxylase gene polymorphisms affect the motor response to L-dopa in Parkinson's disease. AB - BACKGROUND: In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). OBJECTIVE: To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). METHODS: Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCDeltaUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. RESULTS: When adjusted for the L-dopa dose, the AUCDeltaUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. DISCUSSION: The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease. PMID- 24216089 TI - Tyrosinase and Layer-by-Layer supported tyrosinases in the synthesis of lipophilic catechols with antiinfluenza activity. AB - Catechol derivatives with lipophilic properties have been selectively synthesized by tyrosinase in high yield avoiding long and tedious protection/deprotection steps usually required in traditional procedures. The synthesis was effective also with immobilized tyrosinase able to perform for more runs. The novel catechols were evaluated against influenza A virus, that continue to represent a severe threat worldwide. A significant antiviral activity was observed in derivatives characterized by antioxidant activity and long carbon alkyl side chains, suggesting the possibility of a new inhibition mechanism based on both redox and lipophilic properties. PMID- 24216090 TI - Heptaoxygenated xanthones as anti-austerity agents from Securidaca longepedunculata. AB - In a course of our search for anticancer agent based on a novel anti-austerity strategy, we found that the CHCl3 extract of the roots of Securidaca longepedunculata (Polygalaceae), collected at Democratic Republic of Congo, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation on the CHCl3 extract led to the isolation of 28 compounds including five new polymethoxylated xanthones [1,6,8 trihydroxy-2,3,4,5-tetramethoxyxanthone (1), 1,6-dihydroxy-2,3,4,5,8 pentamethoxyxanthone (2), 8-hydroxy-1,4,5,6-tetramethoxy-2,3 methylenedioxyxanthone (3), 4,6,8-trihydroxy-1,2,3,5-tetramethoxyxanthone (4), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (5)] and a new benzyl benzoate [benzyl 3-hydroxy-2-methoxybenzoate (6)]. Among them, 1,6,8-trihydroxy-2,3,4,5 tetramethoxyxanthone (1) and 1,6-dihydroxy-2,3,4,5,8-pentamethoxyxanthone (2) displayed the potent preferential cytotoxicity with PC50 of 22.8 and 17.4 MUM, respectively. They triggered apoptosis-like PANC-1 cell death in NDM with a glucose-sensitive mode. PMID- 24216091 TI - Structure-based design, synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors. AB - To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c Met and VEGFR2 enzyme activities (IC50=1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50=5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C]=4%, po, 5mg/kg, once-daily) and COLO205 (T/C=13%, po, 15 mg/kg, once-daily) mouse xenograft models. PMID- 24216092 TI - Synthesis of vitamin D3 analogues with A-ring modifications to directly measure vitamin D levels in biological samples. AB - C-3-substituted 25-hydroxyvitamin D3 analogues were synthesized as tools to directly measure levels of vitamin D in biological samples. The strategy involves vinyloxycarbonylation of the 3beta-hydroxy group and formation of a carbamate bond with a hydroxyl or amino group at the end of the alkyl chain. Biotinylated conjugates of synthesized derivatives were generated to be linked with vitamin D binding protein (DBP). The spacer group present in the alkyl chain is important in the binding of antibodies to the analogue-DBP complex. When compared to 25 hydroxyvitamin D3-DBP, the binding of some antibodies to the analogue-DBP complex of the 25-hydroxyvitamin D3 derivative 10 that posses an 8-aminoctyl alkyl chain is significantly reduced, but this analogue displaced [26,27-(3)H]-25 hydroxyvitamin D3 from DBP. In contrast, the 8-hydroxyoctyl alkyl chain analogue 9 showed less displacement. PMID- 24216093 TI - Effect of Ala replacement with Aib in amphipathic cell-penetrating peptide on oligonucleotide delivery into cells. AB - A number of cell-penetrating peptides (CPPs) have been characterized and their usefulness as delivery tools has been clarified. As one of the CPPs, model amphipathic peptide (MAP) was developed by integrating both hydrophobic and hydrophilic amino acids in its sequence. In our previous work, we designed MAP(Aib) by replacing five alanine (Ala) residues on the hydrophobic face of the helix in the MAP sequence with alpha-aminoisobutyric acid (Aib) residues, and the replacement resulted in higher helix propensity, stronger resistance to protease, and higher cell membrane permeability than MAP. As a next step, we examined the efficiency of oligonucleotide (ODN) delivery into cells by MAP(Aib) in comparison with that by MAP. The electrostatically formed MAP(Aib)/ODN complex was more easily taken up by cells than the MAP/ODN complex, and the ODN delivery by MAP(Aib) was via an endocytic pathway. We demonstrated that the incorporation of Aib residues into CPPs enhances the delivery of hydrophilic molecules, such as ODN, into cells. PMID- 24216094 TI - Isoquinoline derivatives as potent CRTH2 antagonists: design, synthesis and SAR. AB - In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50=19 nM) in addition to the excellent functional antagonist activity (IC50=13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50=23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 MUM) or the enzymes COX-1 and COX-2 (IC50 >10 MUM). PMID- 24216095 TI - Antioxidant activities of 5-hydroxyoxindole and its 3-hydroxy-3-phenacyl derivatives: the suppression of lipid peroxidation and intracellular oxidative stress. AB - The antioxidant activities of 5-hydroxyoxindole (1) and newly synthesized 3,5 dihydroxy-3-phenacyl-2-oxindole derivatives against rat liver microsome/tert butylhydroperoxide system-induced lipid peroxidation and hydrogen peroxide induced intracellular oxidative stress were investigated. Compound 1 and its derivatives showed significant suppression of lipid peroxidation and an intracellular oxidative stress. The effects of the more lipophilic derivatives tended to be greater than that of the original compound 1. The cytotoxicity of all of the oxindole derivatives on human promyelocytic leukemia HL60 cells was lower than that of 2,6-di(tert-butyl)-4-hydroxytoluene (BHT), a widely used phenolic antioxidant. These results show that compound 1 and its 3-substituted derivatives could be good lead candidates for future novel antioxidant therapeutics. PMID- 24216100 TI - Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome. AB - BACKGROUND: The definition of response to cardiac resynchronization therapy (CRT) remains controversial, with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response. METHODS AND RESULTS: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV) end-systolic volume of >=15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters. CONCLUSIONS: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect. PMID- 24216101 TI - Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes. AB - BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF. METHODS AND RESULTS: Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 +/- 9.7 to 2.2 +/- 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 +/- 45 vs 144 +/- 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate <=65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E' >=15 (OR 3.78, 95% CI 1.26-17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) <=60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR <=60 mg/dL and WRF during UF have an extremely high 1-year mortality rate. PMID- 24216102 TI - Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation. AB - NAD is an important cofactor involved in multiple metabolic reactions and as a substrate for several NAD-dependent signalling enzymes. One such enzyme is CD38 which, alongside synthesising Ca(2+)-releasing second messengers and acting as a cell surface receptor, has also been suggested to play a key role in NAD(+) homeostasis. CD38 is well known as a negative prognostic marker in B-CLL but the role of its enzymatic activity has not been studied in depth to date. We have exploited the HL-60 cell line as a model of inducible CD38 expression, to investigate CD38-mediated regulation intracellular NAD(+) levels and the consequences of changes in NAD(+) levels on cell physiology. Intracellular NAD(+) levels fell with increasing CD38 expression and this was reversed with the CD38 inhibitor, kuromanin confirming the key role of CD38 in NAD(+) homeostasis. We also measured the consequences of CD38 expression during the differentiation on a number of functions linked to NAD(+) and we show that some but not all NAD(+) dependent processes are significantly affected by the lowered NAD(+) levels. These data suggest that both functional roles of CD38 might be important in the pathogenesis of B-CLL. PMID- 24216103 TI - Highly stable maintenance of a mouse artificial chromosome in human cells and mice. AB - Human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) display several advantages as gene delivery vectors, such as stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Previously, we showed that a MAC vector developed from a natural mouse chromosome by chromosome engineering was more stably maintained in adult tissues and hematopoietic cells in mice than HAC vectors. In this study, to expand the utility for a gene delivery vector in human cells and mice, we investigated the long-term stability of the MACs in cultured human cells and transchromosomic mice. We also investigated the chromosomal copy number-dependent expression of genes on the MACs in mice. The MAC was stably maintained in human HT1080 cells in vitro during long-term culture. The MAC was stably maintained at least to the F8 and F4 generations in ICR and C57BL/6 backgrounds, respectively. The MAC was also stably maintained in hematopoietic cells and tissues derived from old mice. Transchromosomic mice containing two or four copies of the MAC were generated by breeding. The DNA contents were comparable to the copy number of the MACs in each tissue examined, and the expression of the EGFP gene on the MAC was dependent on the chromosomal copy number. Therefore, the MAC vector may be useful not only for gene delivery in mammalian cells but also for animal transgenesis. PMID- 24216104 TI - Carvedilol, a third-generation beta-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells. AB - Carvedilol, a nonselective beta-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2mM and H2O2 600 MUM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H2O2. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H2O2-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway. PMID- 24216105 TI - Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration. AB - Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration. PMID- 24216106 TI - Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy. AB - Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Alpha-lipoic acid (LA) plays an important role in the etiology of cardiovascular disease. Autophagy is widely implicated in myocardial I/R injury. We assessed the degree of autophagy by pretreatment with LA exposed to H/R in H9c2 cell based on the expression levels of Beclin-1, LC3II/LC3I, and green fluorescent protein-labeled LC3 fusion proteins. Autophagic vacuoles were confirmed in H9c2 cells exposed to H/R using transmission electron microscopy. Our findings indicated that pretreatment with LA inhibited the degree of autophagy in parallel to the enhanced cell survival and decreased total cell death in H9c2 cells exposed to H/R. We conclude that LA protects cardiomyocytes against H/R injury by inhibiting autophagy. PMID- 24216107 TI - Quercetin-3-O-glucuronide induces ABCA1 expression by LXRalpha activation in murine macrophages. AB - Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRalpha), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRalpha in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin. PMID- 24216108 TI - Down-regulation of Fas-mediated apoptosis by plasma transglutaminase factor XIII that catalyzes fetal-specific cross-link of the Fas molecule. AB - The Fas antigen, also designated as APO-1 or CD95, is a member of the tumor necrosis factor receptor superfamily and can mediate apoptotic cell death in various cells. We report here that blood coagulation factor XIII (plasma transglutaminase, fibrin stabilizing factor) inhibits apoptosis induced by a cytotoxic anti-Fas monoclonal antibody in Jurkat cells. When cells were treated with the antibody in fetal calf serum-containing media, higher-molecular-weight (180K) polypeptides containing Fas molecule were detected by immunoblotting. Under conditions where the transglutaminase activity was eliminated or suppressed, the cross-link of Fas was not observed, and concurrently cell death was hastened. Moreover, an antibody against factor XIII strongly accelerated the Fas-mediated apoptosis. Furthermore, addition of partially purified factor XIII neutralized the apoptosis-promoting effect of anti-factor XIII antibody, indicating that this enzyme is involved in cross-link of Fas and down-regulates Fas-mediated apoptotic cell death. Significantly, the cross-link of Fas was seen only in fetal calf serum but not in newly-born calf serum, 1-year-old calf serum or adult bovine serum. These data suggest that plasma transglutaminase factor XIII may play a key role in fetal development of vertebrates via cross-link of Fas antigen. PMID- 24216109 TI - Cytochrome c(6B) of Synechococcus sp. WH 8102--crystal structure and basic properties of novel c(6)-like family representative. AB - Cytochromes c are soluble electron carriers of relatively low molecular weight, containing single heme moiety. In cyanobacteria cytochrome c6 participates in electron transfer from cytochrome b6f complex to photosystem I. Recent phylogenetic analysis revealed the existence of a few families of proteins homologous to the previously mentioned. Cytochrome c6A from Arabidopsis thaliana was identified as a protein responsible for disulfide bond formation in response to intracellular redox state changes and c550 is well known element of photosystem II. However, function of cytochromes marked as c6B, c6C and cM as well as the physiological process in which they take a part still remain unidentified. Here we present the first structural and biophysical analysis of cytochrome from the c6B family from mesophilic cyanobacteria Synechococcus sp. WH 8102. Purified protein was crystallized and its structure was refined at 1.4 A resolution. Overall architecture of this polypeptide resembles typical I-class cytochromes c. The main features, that distinguish described protein from cytochrome c6, are slightly red-shifted alpha band of UV-Vis spectrum as well as relatively low midpoint potential (113.2+/-2.2 mV). Although, physiological function of cytochrome c6B has yet to be determined its properties probably exclude the participation of this protein in electron trafficking between b6f complex and photosystem I. PMID- 24216110 TI - Functional roles of BCAR3 in the signaling pathways of insulin leading to DNA synthesis, membrane ruffling and GLUT4 translocation. AB - Breast cancer anti-estrogen resistance 3 (BCAR3) is an SH2-containing signal transducer and is implicated in tumorigenesis of breast cancer cells. In this study, we found that BCAR3 mediates the induction of ERK activation and DNA synthesis by insulin, but not by IGF-1. Specifically, the SH2 domain of BCAR3 is involved in insulin-stimulated DNA synthesis. Differential tyrosine phosphorylated patterns of the BCAR3 immune complex were detected in insulin and IGF-1 signaling, suggesting that BCAR3 is a distinct target molecule of insulin and IGF-1 signaling. Moreover, microinjection of BCAR3 inhibitory materials inhibited membrane ruffling induced by insulin, while this did not affect insulin mediated GLUT4 translocation. Taken together, these results demonstrated that BCAR3 plays an important role in the signaling pathways of insulin leading to cell cycle progression and cytoskeleton reorganization, but not GLUT4 translocation. PMID- 24216111 TI - The interaction of Hsp104 with yeast prion Sup35 as analyzed by fluorescence cross-correlation spectroscopy. AB - Prions are self-propagating amyloids. Yeast prion [PSI(+)] is a protein-based heritable element, in which amyloid aggregates of the Sup35 protein are transmitted to daughter cells. Hsp104, an ATP-dependent disaggregase, and other chaperones are essential to maintain [PSI(+)]. Although previous reports have demonstrated the physical interactions of Hsp104 and Sup35 amyloids, the mechanism how Hsp104 interacts with Sup35 amyloids remains to be elucidated. Here we investigated the interaction between Hsp104 and Sup35 in the lysates of [PSI(+)] cells using fluorescence cross-correlation spectroscopy (FCCS), which can analyze the codiffusion events of different fluorophores. FCCS analysis showed a strong interaction between Hsp104 and Sup35 in [PSI(+)] lysates, but not in [psi(-)] lysates, suggesting that Hsp104 recognizes the amyloid aggregates of Sup35. Although the interaction was retained in ATP-depleted [PSI(+)] lysates, addition of ATP or guanidine hydrochloride, which is an inhibitor of Hsp104, to [PSI(+)] lysates weakened the interaction. PMID- 24216112 TI - Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles. AB - Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin. PMID- 24216113 TI - Acupuncture for patients with mild hypertension: study protocol of an open-label multicenter randomized controlled trial. AB - BACKGROUND: Several studies using acupuncture to treat essential hypertension have been carried out. However, whether acupuncture is efficacious for hypertension is still controversial. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for patients with mild hypertension. METHODS/DESIGN: This is a large scale, open-label, multicenter, randomized controlled clinical trial with four parallel arms. We will recruit 428 hypertensive patients with systolic blood pressure (SBP) between 140 and 159 mmHg, diastolic blood pressure (DBP) between 90 and 99 mmHg. The participants will be randomly assigned to four different groups (three acupuncture groups and one waiting list group) (1).The affected meridian acupuncture group (n = 107) is treated with acupoints on the affected meridians (2).The non-affected meridian acupuncture group (n = 107) is treated with acupoints on the non-affected meridians (3).The invasive sham acupuncture group (n = 107) is provided with sham acupoints treatment (4).The waiting-list group (n = 107) is not offered any intervention until they complete the trial. Each patient allocated to acupuncture groups will receive 18 sessions of acupuncture treatment over 6 weeks. This trial will be conducted in 11 hospitals in China. The primary endpoint is the change in average 24-hSBP before and 6 weeks after randomization. The secondary endpoints are average SBP and average DBP during the daytime and night-time, and 36-Item Short Form Survey (SF-36), and so on. DISCUSSION: This is the first large scale, multicenter, randomized, sham controlled trial of acupuncture for essential hypertension in China. It may clarify the efficacy of acupuncture as a treatment for mild hypertension. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01701726. PMID- 24216117 TI - Growth and characterisation of crystals of a new organic complex of thiourea with quinine sulphate dihydrate: an NLO material. AB - An organic complex of thiourea and quinine sulphate dihydrate (TQS) has been grown for the first time by gel method. The structure determination was done by the single crystal XRD technique. The crystal belongs to monoclinic system, P21 space group with cell dimensions a=6.228 (3) A, b=20.4051 (4) A, c=11.0600 (6) A, beta=101.9811(2) degrees . The crystal structure is stabilized by the hydrogen bonding. The functional groups present in the complex were analysed by the Fourier Transform Infrared spectroscopic method. The stoichiometry of the complex was confirmed by the elemental analysis. Thermal properties of the complex were determined by TGA and DTA methods and the complex melts at 222.53 degrees C. The optical transparency of the crystal was studied using UV-Visible absorption spectra. The optical band gap is found to be 2.5 eV. The SHG conversion efficiency of TQS was investigated using Kurtz and Perry method and found to be higher than that of the reference material, potassium dihydrogen phosphate (KDP). PMID- 24216118 TI - Spectroscopy analysis of chitosan-glibenclamide hydrogels. AB - The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino)carbonyl] aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug, has been studied both chitosan using theoretical calculations like Gibbs free energy, electrostatic potential, FTIR and NMR spectroscopy. Fourier transform infrared (FT-IR) spectroscopy reveals information about the molecular interactions of chemical components and is useful to characterization of hydrogel. Nucleophilic and electrophilic regions were calculated using the electrostatic potential. PMID- 24216119 TI - Application properties of oral gels as media for administration of minitablets and pellets to paediatric patients. AB - Modern solid multiparticulate drug forms (minitablets, pellets, granules) can provide the possibility of precise dosing or modified drug release or taste masking for medicines used in children. However, these solid particles require an adequate medium to ease swallowing. The aim of the research was to design a universal semisolid dispersing medium for administration of minitablets and pellets. High viscosity sodium carmellose and carbomer were considered as gelling agents. The hydrogels were prepared with sucrose, glycerol, and potassium sorbate or parabens. Preliminary studies were undertaken to estimate the application properties of the gels under conditions where a medicine is administered to a child. Besides standard tests (viscosity, sedimentation) the following measurements were conducted: gel ductility, mass of the gel removed from a spoon under shaking, ability of the gels to disperse solid particles, and disintegration of minitablets in the gels. The oral hydrogels prepared either with 1.0% and 1.5% carmellose or 0.25% and 0.5% (w/w) carbomer were suitable for dispersing and delivery of minitablets or pellets. Not only viscosity but also ductility was an essential criterion in selecting the best vehicle. The in vivo perceptibility test for pellets and minitablets did not confirm that gels are more advantageous than syrups. PMID- 24216120 TI - [Community health: action needed]. PMID- 24216121 TI - [Farewell to paper in Gaceta Sanitaria]. PMID- 24216122 TI - Impact of early adversity on glucocorticoid regulation and later mental disorders. AB - Early adverse experiences such as abuse or neglect can influence brain development and consequently bring forth a predisposition toward mental and behavioral disorders. Many authors suggest that long-term changes in the functionality of the HPA axis might be involved in mediating this relationship. The direction of change and its consequences have not been clarified though: Do early adverse experiences yield a stable glucocorticoid hyperfunction or a long term glucocorticoid hypofunction, and how is this change of functionality associated with mental or behavioral disorders? This review summarizes correlative findings and illustrates inconsistencies of current research literature. It focuses on the specific neurochemical milieu accompanying early adverse experiences and discusses possible interactions of the glucocorticoid system with oxytocin and components of the serotonergic system. On the basis of this physiological view, a novel two-pathway model is presented, according to which specific early experiences are associated with characteristic early changes in the functionality of these systems and result in a predisposition to distinct mental and behavioral disorders. PMID- 24216123 TI - Comparison of transesophageal echocardiography versus computed tomography for detection of left atrial appendage filling defect (thrombus). AB - Patients with atrial fibrillation, who are referred for radiofrequency pulmonary vein antral isolation, frequently undergo transesophageal echocardiography (TEE) to detect and/or exclude left atrial or left atrial appendage (LAA) thrombus and cardiac computed tomographic angiography (CCTA) to define and/or evaluate left atrial and pulmonary venous anatomy. Previous studies have reported CCTA to have high sensitivity and negative predictive value (NPV) for detecting thrombus in the LAA. Previous studies determining an optimal LAA/ascending aorta (AA) Hounsfield unit (HU) density ratio for detection of LAA thrombus have been small, with limited numbers of thrombi. We thus sought to determine both the optimal cutoff for LAA HU density and LAA/AA HU density ratio in detecting LAA thrombus compared with TEE in a multicenter population. We included 84 patients who had undergone CCTA and TEE. LAA was evaluated by 64-row CCTA qualitatively (visual filling defect) and quantitatively (measurement of LAA HU density and LAA/AA HU density ratio), using a 1-cm area of interest in the same axial plane. Results were compared with TEE visualization of thrombus or spontaneous echo contrast. Qualitative identification of thrombus in LAA by CCTA compared with TEE detection of thrombus had a sensitivity of 100%, a specificity of 77.9%, a positive predictive value (PPV) of 51.6%, an NPV of 100%, and a total accuracy of 82.1%. The optimal LAA HU density cutoff for thrombus detection was 119 with a sensitivity of 88%, a specificity of 86%, PPV 56%, and an area under the curve of 0.923 (p = 0.0004). The optimal LAA/aorta HU ratio was 0.242 with a sensitivity of 87%, a specificity of 88%, a PPV of 64%, and an area under the curve of 0.921 (p = 0.0011). There is no significant difference (p = 0.72) between both areas under the curve, and both measurements improved the specificity and PPV compared with qualitative measures. Multidetector computed tomography is an imaging technique that can exclude LAA thrombus with very high NPV. Quantitative measurement of LAA HU density (cutoff 119) or LAA/aorta HU density ratio (cutoff 0.242) improves accuracy of positively detecting LAA thrombus. This technique is especially useful when delayed scanning is not performed and LAA is found incidentally after the patient scanning is complete. PMID- 24216124 TI - Influence of age-related versus non-age-related renal dysfunction on survival in patients with left ventricular dysfunction. AB - Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m(2) (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m(2)/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m(2), 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p <0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID- 24216125 TI - Comparison of prognosis in unrecognized versus recognized myocardial infarction in men versus women >55 years of age (from the Rotterdam Study). AB - Unrecognized myocardial infarction (MI) is frequent in the general population. Its prognosis is reported to be at least as unpropitious as that of recognized MI, particularly in men. However, contemporary data with long follow-up are lacking. The aims of this study were to investigate the long-term prognosis of unrecognized MI with respect to all-cause and cause-specific mortality and to investigate possible differences in prognosis by gender. In the population-based Rotterdam Study (2,672 men and 3,862 women), the presence of unrecognized MI and recognized MI was determined at baseline (1990 to 1993). The cohort was followed for nearly 2 decades for all-cause and cause-specific mortality. During 82,268 patient-years of follow-up (median 15.6 years) 3,412 patients died (1,300 from cardiovascular causes). Men and women with recognized and unrecognized MIs had increased total mortality rates compared with those without MIs. Hazard ratios (HRs) for men and women were 1.57 (95% confidence interval [CI] 1.36 to 1.81) and 1.89 (95% CI 1.56 to 2.30) for recognized MI and 1.72 (95% CI 1.43 to 2.07) and 1.36 (95% CI 1.14 to 1.61) for unrecognized MI. Unrecognized MI was associated with increased risks for cardiovascular mortality (men: HR 2.19, 95% CI 1.66 to 2.91; women: HR 1.36, 95% CI 1.03 to 1.81) and noncardiovascular mortality (men: HR 1.47, 95% CI 1.14 to 1.89; women: HR 1.39, 95% CI 1.10 to 1.75). In conclusion, the long-term prognosis of patients with unrecognized MIs is worse compared with those without MIs and applies not only to cardiovascular mortality but also to noncardiovascular mortality. In men, the prognosis is as unfavorable as that of patients with recognized MIs. PMID- 24216126 TI - Prevalence, correlates, and temporal trends in antiarrhythmic drug use at discharge after implantable cardioverter defibrillator placement (from the National Cardiovascular Data Registry [NCDR]). AB - Patients with implantable cardioverter defibrillators (ICDs) can require antiarrhythmic drugs to manage arrhythmias and prevent device shocks. We sought to determine the prevalence, clinical correlates, and institutional variation in the use of antiarrhythmic drugs over time after ICD implantation. From the ICD Registry (2006 to 2011), we analyzed the trends in the use of antiarrhythmic agents prescribed at hospital discharge for patients undergoing first-time ICD placement. The patient, provider, and facility level variables associated with antiarrhythmic use were determined using multivariate logistic regression models. A median odds ratio was calculated to assess the hospital-level variation in the use of antiarrhythmic drugs. Of the cohort (n = 500,995), 15% had received an antiarrhythmic drug at discharge. The use of class III agents increased modestly (13.9% to 14.9%, p <0.01). Amiodarone was the most commonly prescribed drug (82%) followed by sotalol (10%). Among the subgroups, the greatest increase in prescribing was for patients who had received a secondary prevention ICD (26% in 2006% and 30% in 2011, p <0.01) or with a history of ventricular tachycardia (23% to 27%, p <0.01). The median odds ratio for antiarrhythmic prescription was 1.45, indicating that 2 randomly selected hospitals would have had a 45% difference in the odds of treating identical patients with an antiarrhythmic drug. In conclusion, antiarrhythmic drug use, particularly class III antiarrhythmic drugs, is common among ICD recipients at hospital discharge and varies by hospital, suggesting an influence from local treatment patterns. The observed hospital variation suggests a role for augmentation of clinical guidelines regarding the use of antiarrhythmic drugs for patients undergoing implantation of an ICD. PMID- 24216127 TI - Electron microscopy of primary cell cultures in solution and correlative optical microscopy using ASEM. AB - Correlative light-electron microscopy of cells in a natural environment of aqueous liquid facilitates high-throughput observation of protein complex formation. ASEM allows the inverted SEM to observe the wet sample from below, while an optical microscope observes it from above quasi-simultaneously. The disposable ASEM dish with a silicon nitride (SiN) film window can be coated variously to realize the primary-culture of substrate-sensitive cells in a few milliliters of culture medium in a stable incubator environment. Neuron differentiation, neural networking, proplatelet-formation and phagocytosis were captured by optical or fluorescence microscopy, and imaged at high resolution by gold-labeled immuno-ASEM with/without metal staining. Fas expression on the cell surface was visualized, correlated to the spatial distribution of F-actin. Axonal partitioning was studied using primary-culture neurons, and presynaptic induction by GluRdelta2-N-terminus-linked fluorescent magnetic beads was correlated to the presynaptic-marker Bassoon. Further, megakaryocytes secreting proplatelets were captured, and P-selectins with adherence activity were localized to some of the granules present by immuno-ASEM. The phagocytosis of lactic acid bacteria by dendritic cells was also imaged. Based on these studies, ASEM correlative microscopy promises to allow the study of various mesoscopic-scale dynamics in the near future. PMID- 24216128 TI - MAVIS: an integrated system for live microscopy and vitrification. AB - Cryo-electron microscopy of vitrified biological samples can provide three dimensional reconstructions of macromolecules and organelles within bacteria and cells at nanometer scale resolution, even in native conditions. Localization of specific structures and imaging of cellular dynamics in cellular cryo-electron microscopy is limited by (i) the use of cryo-fixation to preserve cellular structures, (ii) the restricted availability of electron dense markers to label molecules inside cells and (iii) the inherent low contrast of cryo electron microscopy. These limitations can be mitigated to a large extend by correlative light and electron microscopy, where the sample is imaged by both light and electron microscopy. Here we present a Microscopy and Vitrification Integrated System (MAVIS) that combines a light microscope with a plunger to vitrify thin specimens. MAVIS provides the capability for fluorescence light microscopic imaging of living cells and bacteria that are adhered to an electron microscopy grid and subsequent vitrification within a time frame of seconds. The instrument allows targeting of dynamic biological events in time and space by fluorescence microscopy for subsequent cryo light and electron microscopy. Here we describe the design and performance of the MAVIS, illustrated with biological examples. PMID- 24216129 TI - Value of anatomic site, histology and clinicopathological parameters for prediction of lymph node metastasis and overall survival in head and neck melanomas. AB - INTRODUCTION: Head and neck melanoma compromises a group of aggressive tumours with varying clinical courses. This analysis was performed to find anatomic and clinicopathological parameters predictive for lymph node metastasis and overall survival. MATERIAL AND METHODS: Data and outcome of 246 patients with a malignant melanoma in the head and neck region were retrospectively analyzed for predictive parameters. RESULTS: Lentigo maligna melanoma (n = 115) was the most frequent histology, followed by superficial spreading (n = 63) and nodular melanoma (n = 52). More than half of the melanomas (n = 138) were in the face. Tumours of the face and anterior scalp metastasized to lymph nodes of the neck and parotid gland, whereas tumours of the posterior scalp and neck also metastasized to the nuchal region. Advanced Clark level, presence of tumour ulceration and younger age were the strongest predictors of lymph node metastasis in multivariate regression analysis (p < 0.05), but anatomic site, histological subtype and tumour thickness were also associated with lymph node metastasis. Lymph node metastases, distant metastases, ulceration, nodular subtype and non-facial site of origin were the strongest negative prognostic parameters for disease-specific overall survival (p < 0.05). In contrast, the width of resection margin (<1 cm vs. 1-2 cm vs. >2 cm) did not correlate with tumour recurrence and overall survival (p > 0.05). CONCLUSION: Histological subtype diagnosis, anatomic site of origin as well as the established factors tumour thickness, ulceration and depth of invasion are prognostic indicators of cervical lymph node metastasis and overall survival. A resection margin of at least 1 cm seems sufficient in head and neck melanoma. The status of sentinel lymph node biopsy and neck dissection has to be proven within the next years. PMID- 24216130 TI - MicroRNA-10b overexpression promotes non-small cell lung cancer cell proliferation and invasion. AB - BACKGROUND: miRNAs are a class of small non-coding RNA molecules that play an important role in the pathogenesis of human diseases through negative regulation of gene expression. Although miRNA-10b (miR-10b) has been implicated in other tumors, its role in non-small cell lung cancer (NSCLC) is still unknown. The aim of the present study was to investigate the role of miR-10b in NSCLC. METHODS: Expression of miR-10b was analyzed in NSCLC cell line A549 by qRT-PCR. Cell viability was evaluated using Cell Counting Kit (CCK)-8. Cell migration and invasion were evaluated by wound healing assay and transwell assays. Cell cycle and apoptosis analyses were performed. Western blotting was used to predicate the target of miR-10b. RESULTS: The A549 cell line transfected with the miR-10b exhibited significantly increased proliferation, migration, and invasion capacities when compared with the control cells (P < 0.05). Kruppel-like factor 4 (KLF4) may be indirectly targeted by miR-10b during the proliferation increasing of A549 cells. CONCLUSION: In this study, we found that miR-10b is a tumor enhancer in NSCLC. Thus, miR-10b may represent a potential therapeutic target for NSCLC intervention. PMID- 24216131 TI - Intercellular communications within the rat anterior pituitary. XVI: postnatal changes of distribution of S-100 protein positive cells, connexin 43 and LH-RH positive sites in the pars tuberalis of the rat pituitary gland. An immunohistochemical and electron microscopic study. AB - The architecture of luteinizing hormone-releasing hormone (LH-RH) nerve ends and the S-100 protein containing folliculo-stellate cells forming gap junctions in the pars tuberalis is basically important in understanding the regulation of the hormone producing mechanism of anterior pituitary glands. In this study, intact male rats 5-60 days old were prepared for immunohistochemistry and electron microscopy. From immunostained sections, the S-100 containing cells in pars tuberalis were first detected on day 30 and increased in number to day 60; this was parallel to the immunohistochemical staining of gap junction protein, connexin 43. LH-RH positive sites were clearly observed on just behind the optic chiasm and on the root of pituitary stalk on day 30. On day 60, the width of layer increased, while follicles and gap junctions were frequently observed between agranular cells in 10 or more layers of pars tuberalis. In the present study, we investigated the sexual maturation of the anterior pituitary glands through the postnatal development of S-100 positive cells, connexin 43 and LH-RH nerves. It is suggested that the folliculo-stellate cell system including the LH RH neurons in the pars tuberalis participates in the control of LH secretion along with the portal vein system. PMID- 24216132 TI - Botanical insecticides inspired by plant-herbivore chemical interactions. AB - Plants have evolved a plethora of secondary chemicals to protect themselves against herbivores and pathogens, some of which have been used historically for pest management. The extraction methods used by industry render many phytochemicals ineffective as insecticides despite their bioactivity in the natural context. In this review, we examine how plants use their secondary chemicals in nature and compare this with how they are used as insecticides to understand why the efficacy of botanical insecticides can be so variable. If the commercial production of botanical insecticides is to become a viable pest management option, factors such as production cost, resource availability, and extraction and formulation techniques need be considered alongside innovative application technologies to ensure consistent efficacy of botanical insecticides. PMID- 24216133 TI - Neural regulatory mechanism of desire for food: revealed by magnetoencephalography. AB - Currently, little is known about the brain function that allows individuals to suppress eating behavior. The present study used magnetoencephalography (MEG) to examine changes in neural activity over time that were related to suppression of motivation to eat in 11 healthy males. The MEG experiment consisted of four motivation sessions and four suppression sessions in an alternating and counterbalanced order. During MEG recordings, participants viewed a set of food pictures and mosaic pictures projected onto a screen, and were then asked to rate their motivation to eat and the suppression of the motivation to eat during the recordings. The present study demonstrated a higher beta-band (13-25 Hz) event related synchronization (ERS) level during the suppression sessions relative to the motivation sessions in the left supplementary motor area (SMA) 200-300 ms after the start of food picture presentation. Similar differences were also observed in theta-band (4-8 Hz) event-related desynchronization (ERD) in the left dorsolateral prefrontal cortex (DLPFC) after 500-600 ms. Negative relationships were observed between these levels of MEG responses and the number of food items for which the participants reported the motivation to eat during the MEG recordings. These findings indicate that the left DLPFC and SMA, particularly the DLPFC, play prominent roles in the suppression of motivation to eat. This may help to clarify the temporal aspects of the neural basis of self-control of appetitive motivation as well as aid development of self-control strategies such as cognitive behavioral therapy for patients with disordered appetite. PMID- 24216134 TI - Oxytocin and the social brain: neural mechanisms and perspectives in human research. AB - The present paper summarizes functional imaging studies investigating the effects of intranasal oxytocin (OT) on brain responses to social stimuli. We aim to integrate previous research, point to unresolved issues and highlight perspectives for future studies. The studies so far have focused on identifying neural circuits underlying social information processing which are particularly sensitive to modulations by exogenous OT. Most consistently, stimulus-related responses of the amygdala and associated areas within the prefrontal and temporal cortices have been found to be modulated by OT administration. However, there are a number of unresolved issues related to the possible role of sex differences and hormonal status, genetic variability, and individual differences in socio cognitive functioning. Future studies focusing on these open questions are expected to contribute to a more nuanced understanding of the role of the central OT system in humans and may provide the basis for novel treatment approaches for mental disorders characterized by social deficits. This article is part of a Special Issue entitled Oxytocin and Social Behav. PMID- 24216135 TI - The behavioral effects of acute Delta9-tetrahydrocannabinol and heroin (diacetylmorphine) exposure in adult zebrafish. AB - The use of psychotropic drugs in clinical and translational brain research continues to grow, and the need for novel experimental models and screens is becoming widely recognized. Mounting evidence supports the utility of zebrafish (Danio rerio) for studying various pharmacological manipulations, as an alternative model complementing the existing rodent paradigms in this field. Here, we explore the effects of acute 20-min exposure to two commonly abused psychotropic compounds, Delta(9)-tetrahydrocannabinol (THC) and heroin, on adult zebrafish behavior in the novel tank test. Overall, THC administration (30 and 50 mg/L) produces an anxiogenic-like reduction of top swimming, paralleled with a slower, continuous bottom swimming. In contrast, heroin exposure (15 and 25 mg/L) evoked a hyperlocomotor response (with rapid bouts of bottom swimming and frequent 'bouncing' motions) without altering anxiety-sensitive top/bottom endpoints. The behavioral effects of these two compounds in zebrafish seem to parallel the respective rodent and human findings. Collectively, this emphasizes the growing significance of novel emerging aquatic models in translational drug abuse research and small molecule screening. PMID- 24216136 TI - Hyperphosphorylation of tau protein in the ipsilateral thalamus after focal cortical infarction in rats. AB - Hyperphosphorylation of tau has been considered as an important risk factor for neurodegenerative diseases. It has been found also in the cortex after focal cerebral ischemia. The present study is aimed at investigating changes of tau protein expression in the ipsilateral thalamus remote from the primary ischemic lesion site after distal middle cerebral artery occlusion (MCAO). The number of neurons in the ventroposterior thalamic nucleus (VPN) was evaluated using Nissl staining and neuronal nuclei (NeuN) immunostaining. Total tau and phosphorylated tau at threonine 231 (p-T231-tau) and serine 199 (p-S199-tau) levels, respectively, in the thalamus were measured using immunostaining and immunoblotting. Moreover, apoptosis was detected with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay. It was found that the numbers of intact neurons and NeuN(+) cells within the ipsilateral VPN were reduced significantly compared with the sham-operated group, but the levels of p-T231-tau and p-S199-tau in the ipsilateral thalamus were increased significantly in rats subjected to ischemia for 3 days, 7 days and 28 days. Furthermore, the number of TUNEL-positive cells was increased in the ipsilateral VPN at 7 days and 28 days after MCAO. Thus, hyperphosphorylated tau protein is observed in ipsilateral thalamus after focal cerebral infarction in this study. Our findings suggest that the expression of hyperphosphorylated tau protein induced by ischemia may be associated with the secondary thalamic damage after focal cortical infarction via an apoptotic pathway. PMID- 24216138 TI - Comment on "Morphogenetic action through flux-limited spreading" by Verbeni, Sanchez, Mollica, Siegl-Cachedenier, Carleton, Guerrero, Ruiz i Altaba, and Soler. PMID- 24216140 TI - Isomorphisms between psychological processes and neural mechanisms: from stimulus elements to genetic markers of activity. AB - Traditional learning theory has developed models that can accurately predict and describe the course of learned behavior. These "psychological process" models rely on hypothetical constructs that are usually thought to be not directly measurable or manipulable. Recently, and mostly in parallel, the neural mechanisms underlying learning have been fairly well elucidated. The argument in this essay is that we can successfully uncover isomorphisms between process and mechanism and that this effort will help advance our theories about both processes and mechanisms. We start with a brief review of error-correction circuits as a successful example. Then we turn to the concept of stimulus elements, where the conditional stimulus is hypothesized to be constructed of a multitude of elements only some of which are sampled during any given experience. We discuss such elements with respect to how they explain acquisition of associative strength as an incremental process. Then we propose that for fear conditioning, stimulus elements and basolateral amygdala projection neurons are isomorphic and that the activational state of these "elements" can be monitored by the expression of the mRNA for activity-regulated cytoskeletal protein (ARC). Finally we apply these ideas to analyze recent data examining ARC expression during contextual fear conditioning and find that there are indeed many similarities between stimulus elements and amygdala neurons. The data also suggest some revisions in the conceptualization of how the population of stimulus elements is sampled from. PMID- 24216141 TI - Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up. AB - PURPOSE: We have previously shown the feasibility of delivering high doses of radiotherapy in malignant pleural mesothelioma (MPM) patients who underwent radical pleurectomy/decortication (P/D) or surgical biopsy. In this report, we present the long-term results of MPM patients treated with radical P/D followed by high doses of radiotherapy. METHODS AND MATERIALS: Twenty consecutive MPM patients were enrolled in this prospective study and underwent radical P/D followed by high dose radiotherapy. The clinical target volume was defined as the entire hemithorax excluding the intact lung. The dose prescribed was 50 Gy in 25 fractions. Any FDG-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Nineteen patients received cisplatin/pemetrexed chemotherapy. Kaplan-Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), and loco regional control (LRC). RESULTS: The median follow-up was of 27 months. The median OS and PFS were 33 and 29 months, respectively. The median LRC was not reached. The Kaplan-Meier estimates of OS at 2 and 3 years were 70% and 49%, respectively. The estimates of PFS at 2 and 3 years were 65% and 46%, respectively. The estimates of LRC at 2 and 3 years were 68% and 59%, respectively. The predominant pattern of failure was distant: 7 patients developed distant metastases as the first site of relapse, whereas only 3 patients experienced an isolated loco-regional recurrence. No fatal toxicity was reported. Five Grades 2-3 pneumonitis were documented. CONCLUSIONS: High dose radiation therapy following radical P/D led to excellent loco-regional control and survival results in MPM patients. A median OS of 33 months and a 3-year OS rate of 49% are among the best observed in recent studies, supporting the idea that this approach represents a concrete therapeutic option for malignant pleural mesothelioma. PMID- 24216142 TI - Aminoglycosides and ototoxicity in neonates: is there a relation with serum concentrations? PMID- 24216139 TI - Decision Aid to Technologically Enhance Shared decision making (DATES): study protocol for a randomized controlled trial. AB - BACKGROUND: Clinicians face challenges in promoting colorectal cancer screening due to multiple competing demands. A decision aid that clarifies patient preferences and improves decision quality can aid shared decision making and be effective at increasing colorectal cancer screening rates. However, exactly how such an intervention improves shared decision making is unclear. This study, funded by the National Cancer Institute, seeks to provide detailed understanding of how an interactive decision aid that elicits patient's risks and preferences impacts patient-clinician communication and shared decision making, and ultimately colorectal cancer screening adherence. METHODS/DESIGN: This is a two armed single-blinded randomized controlled trial with the target of 300 patients per arm. The setting is eleven community and three academic primary care practices in Metro Detroit. Patients are men and women aged between 50 and 75 years who are not up to date on colorectal cancer screening. ColoDATES Web (intervention arm), a decision aid that incorporates interactive personal risk assessment and preference clarification tools, is compared to a non-interactive website that matches ColoDATES Web in content but does not contain interactive tools (control arm). Primary outcomes are patient uptake of colorectal cancer screening; patient decision quality (knowledge, preference clarification, intent); clinician's degree of shared decision making; and patient-clinician concordance in the screening test chosen. Secondary outcome incorporates a Structural Equation Modeling approach to understand the mechanism of the causal pathway and test the validity of the proposed conceptual model based on Theory of Planned Behavior. Clinicians and those performing the analysis are blinded to arms. DISCUSSION: The central hypothesis is that ColoDATES Web will improve colorectal cancer screening adherence through improvement in patient behavioral factors, shared decision making between the patient and the clinician, and concordance between the patient's and clinician's preferred colorectal cancer screening test. The results of this study will be among the first to examine the effect of a real-time preference assessment exercise on colorectal cancer screening and mediators, and, in doing so, will shed light on the patient clinician communication and shared decision making 'black box' that currently exists between the delivery of decision aids to patients and subsequent patient behavior. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01514786. PMID- 24216143 TI - microRNA expression profiles distinguish colorectal cancer patients in two regions of Austria. PMID- 24216144 TI - A systems pharmacology approach to improve drug therapy in NSCLC: establishing a CESAR network. PMID- 24216145 TI - Circulating tumor cell composition and outcome in patients with solid tumors. PMID- 24216146 TI - How is intensive care reimbursed? A review of eight European countries. AB - Reimbursement schemes in intensive care are more complex than in other areas of healthcare, due to special procedures and high care needs. Knowledge regarding the principles of functioning in other countries can lead to increased understanding and awareness of potential for improvement. This can be achieved through mutual exchange of solutions found in other countries. In this review, experts from eight European countries explain their respective intensive care unit reimbursement schemes. Important conclusions include the apparent differences in the countries' reimbursement schemes-despite all of them originating from a DRG system-, the high degree of complexity found, and the difficulties faced in several countries when collecting the data for this collaborative work. This review has been designed to assist the intensivist clinician and researcher in understanding neighbouring countries' approaches and in putting research into the context of a European perspective. In addition, steering committees and decision makers might find this a valuable source to compare different reimbursement schemes. PMID- 24216147 TI - A medical education as an investment: financial food for thought. AB - Every year that the training period can be shortened increases the value of a medical education. Tuition covers only a fraction of the cost of medical education, making the societal investment in older students less financially robust. Shortening training periods would immediately solve the shortage of residency training positions. With a few exceptions, a medical education is a good investment for women. We are skeptical of the proposals to address the skyrocketing student debt because they do not confront the primary problem. The best way to minimize debt is thrift, and the best way to make a career in medicine more desirable is to shorten the training time. PMID- 24216148 TI - Pediatric fronto-orbital cemento-ossifying fibroma: a report of two cases. PMID- 24216149 TI - Immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus. AB - OBJECTIVE: Pathogenesis of pseudohypertrophy of the inferior olivary nucleus (PH IO) was analyzed based on immunohistochemical study. METHODS: Immunostained medullas with PH-IO were observed with confocal laser microscopy. RESULTS: alphaB crystallin (alphaBC) was frequently expressed in the neurons and co-localized with microtubule-associated protein 2 (MAP2). The neurons were occasionally positive for SMI-31. alphaBC and SMI-31 were co-localized in some neurons. Synaptophysin (SYP)-immunoreactive dots were present around MAP2-positive hypertrophic neurons and hypertrophic thick neurites. Periphery-stained Lys-Asp Glu-Leu (KDEL)-positive neurons were shown. Central chromatolytic neurons were found with Kluver-Barrera staining, which indicated that the rough endoplasmic reticulum (ER) was distributed to the periphery of the cytoplasm. CONCLUSIONS: alphaBC prevents microtubule disassembly and phosphorylation of the neurofilaments under stressful conditions. Our results indicated that alphaBC protected microtubules and neurofilaments in PH-IO. The retrograde transport of KDEL receptors from the Golgi complex to the ER is increased under stressful conditions. We considered that KDEL receptors were retro-transported to ER, and then the ER containing KDEL receptors was distributed to the periphery of the cytoplasm. PH-IO showed various immunohistochemical changes due to trans-synaptic degeneration. PMID- 24216150 TI - Ion Beam Induced Luminescence capabilities for the analysis of coarse-grained river sediments. AB - In this work the Ion Beam Induced Luminescence (IBIL) capabilities for the analysis of geological mobile sediment samples from the beds of three major rivers flowing in the Veneto Region (North-Eastern Italy) is presented in the first application of this technique to characterize such samples. Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) spectra were also measured and discussed to give indications for the identification of the main luminescence features. The evolution of the different IBIL components with the irradiation dose was studied and their correlation to matrix defects outlined. Finally, a Principal Component Analysis (PCA) of the IBIL evolving spectra was performed to verify the capability of this approach to discriminate among the different samples. PMID- 24216151 TI - Spectroscopy and visible frequency upconversion in Er3+-Yb3+: TeO2-ZnO glass. AB - The UV-Vis-NIR absorption studies of the Er(3+)/Er(3+)-Yb(3+) doped/codoped TeO2 ZnO (TZO) glasses fabricated by the melting and quenching method has been performed. The spectroscopic radiative parameters viz. radiative transition probabilities, branching ratios and lifetimes have been determined from the absorption spectrum by using Judd-Ofelt theory. The near infrared (NIR) to visible frequency upconversion (UC) have been monitored by using an excitation of 976 nm wavelength radiation from a CW diode laser. The effect of codoping with Yb(3+) ions on the intensity of the UC emission bands from the Er(3+) ions throughout visible region has been studied. The mechanism responsible for the observed upconversion emissions in the prepared samples have been explained on the basis of excited state absorption and efficient energy transfer processes. PMID- 24216152 TI - Common Prairie feeds with different soluble and insoluble fractions used for CPM diet formulation in dairy cattle: impact of carbohydrate-protein matrix structure on protein and other primary nutrient digestion. AB - An experiment was conducted to investigate the relationship of carbohydrates molecular spectral characteristics to rumen degradability of primary nutrients in Prairie feeds in dairy cattle. In total, 12 different types of feeds were selected, each type of feed was from three different source with total 37 samples. Six types of them were energy-sourced feeds and the others were protein sourced feeds. The carbohydrates molecular spectral intensity of various functional groups were collected using Fourier transform infrared attenuated total reflectance (ATR-FT/IR) spectroscopy. In the in situ study, the results showed that the rumen digestibility and digestible fractions of primary nutrients (DM, OM, NCP, and CP) were significantly different (P<0.05) among the feeds. The spectral bands features were significantly different (P<0.05) among the feeds. Spectral intensities of A_Cell, H_1415 and H_1370 were weakly positively correlated with in situ rumen digestibility and digestible fractions of DM, OM and NCP. Spectral intensities of H_1150, H_1015, A_1, and A_3 were weakly negatively associated with in situ rumen degradation of CP. Spectral intensities of A_1240 and H_1240, mainly associated with cellulosic compounds, were correlated with rumen CP degradation. The multiple regression analysis demonstrated that the spectral intensities of A_3 and H_1415 played the most important role and could be used as a potential tool to predict rumen protein degradation of feeds in dairy cattle. In conclusion, this study showed that the carbohydrates as a whole have an effect on protein rumen degradation, rather than cellulose alone, indicating carbohydrate-protein matrix structure impact protein utilization in dairy cattle. The non-invasive molecular spectral technique (ATR FT/IR) could be used as a rapid potential tool to predict rumen protein degradation of feedstuffs by using molecular spectral bands intensities in carbohydrate fingerprint region. PMID- 24216154 TI - How to link pyrene to its host lipid to minimize the extent of membrane perturbations and to optimize pyrene dimer formation. AB - We study how lipid probes based on pyrene-labeling could be designed to minimize perturbations in lipid bilayers, and how the same design principles could be exploited to develop probes which gauge lipid dynamics primarily within a single lipid monolayer or between them. To this end, we use atomistic molecular dynamics simulations to consider membranes where pyrene moieties are attached to lipid acyl chains in varying positions. We find that in a DOPC bilayer the conformational ordering of lipids around di-pyrenyl-PC probes is altered to a largely similar extent regardless of where the pyrene moiety is attached to the hydrocarbon chain. This is in contrast to saturated membranes, where pyrene induced perturbations have been observed to be more prominent. Meanwhile, the formation of pyrene dimers depends on the linkage point between pyrene and its host lipid. Membrane-spanning dimers between lipids in different membrane leaflets are observed only if the pyrene moiety is attached to the latter half of the acyl chain. A seemingly minor change to link pyrene to an acyl chain that is two carbons shorter leads to a situation where membrane-spanning dimers are no longer observed. Further, simulations suggest that formation of dimers is a slow process, where the rate is limited by both lateral diffusion and the dimerization process once the two probes are neighbors to one another. Typical lifetimes of pyrene dimers turn out be of the order of nanoseconds. The results are expected to pave the way for designing ways to consider experimentally topics such as intraleaflet lateral diffusion, motion of lipids within and between membrane domains, and membrane domain registration across bilayers. PMID- 24216153 TI - Modulated photophysics of a cationic DNA-staining dye inside protein bovine serum albumin: study of binding interaction and structural changes of protein. AB - The binding affinity of cationic DNA-staining dye, propidium iodide, with transport protein, bovine serum albumin, has been explored using UV-vis absorption, fluorescence, and circular dichroism spectroscopy. Steady state and time resolved fluorescence studies authenticate that fluorescence quenching of bovine serum albumin by propidium iodide is due to bovine serum albumin-propidium iodide complex formation. Thermodynamic parameters obtained from temperature dependent spectral studies cast light on binding interaction between the probe and protein. Site marker competitive binding has been encountered using phenylbutazone and flufenamic acid for site I and site II, respectively. Energy transfer efficiency and distance between bovine serum albumin and propidium iodide have been determined using Forster mechanism. Structural stabilization or destabilization of protein by propidium iodide has been investigated by urea denaturation study. The circular dichroism study as well as FT-IR measurement demonstrates some configurational changes of the protein in presence of the dye. Docking studies support the experimental data thereby reinforcing the binding site of the probe to the subdomain IIA of bovine serum albumin. PMID- 24216155 TI - Isolation, pathogenicity and disinfection of Staphylococcus aureus carried by insects in two public hospitals of Vitoria da Conquista, Bahia, Brazil. AB - Currently, hospital infection is a serious public health problem, and several factors may influence the occurrence of these infections, including the presence of insects, which are carriers of multidrug-resistant bacterial species. The aim of this study was to isolate staphylococci carried by insects in two public hospitals of Vitoria da Conquista, Bahia and to identify the resistance profile, pathogenicity and efficacy of disinfection of the premises. A total of 91 insects were collected in 21 strategic points of these hospitals, and 32 isolated strains of Staphylococcus aureus were isolated. Based on antibiogram and Minimum Inhibitory Concentration results, 95% of these strains were susceptible to oxacillin. These strains were also evaluated for the presence of resistance genes encoding resistance to oxacillin/methicillin by polymerase chain reaction, but the sample was negative for this gene. Pathogenicity tests were performed in vitro biofilm formation induced by glucose, where it was found that eight (27.58%) strains were classified as biofilm producers and 21 (72.4%) as stronger producers. In addition, we performed PCR for their virulence genes: Sea (enterotoxin A), SEB (B), Sec (C), PVL (Panton-Valentine Leukocidin), ClfA (clumping factor A) and Spa (protein A). Of these, Sea, Spa PVL were positive in 7 (21.8%), 2 (6.3%) and 1 (3.1%) samples, respectively. The analysis of cytokine induction in the inflammatory response of J774 macrophages by isolates from the two hospitals did not show statistical difference at the levels of IL-6, TNF alpha, IL-1 and IL-10 production. In addition, we verified the antimicrobial activity of disinfecting agents on these strains, quaternary ammonium, 0.5% sodium hypochlorite, 1% sodium hypochlorite, 2% sodium hypochlorite, 2% glutaraldehyde, Lysoform((r)), 70% alcohol solution of chlorhexidine digluconate, 2% peracetic acid, and 100% vinegar. Resistance was seen in only for the following two disinfectants: 70% alcohol in 31 (96.8%) samples tested and vinegar in 30 (93.8%) samples. The study demonstrated the presence of resistant and pathogenic organisms conveyed by insects, thus suggesting improvement in efforts to control these vectors. PMID- 24216156 TI - Chlamydia trachomatis in human immunodeficiency virus-infected men treated at a referral hospital for sexually transmitted diseases in the Amazonas, Brazil. AB - OBJECTIVES: The aim of the present study was to determine the Chlamydia trachomatis prevalence and to identify the demographic, behavioural and clinical factors associated with C. trachomatis in human immunodeficiency virus infected men. STUDY: This was a cross-sectional study of C. trachomatis prevalence among human immunodeficiency virus-infected men enrolled at the Outpatient clinic of acquired immunodeficiency syndrome of the Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil. C. trachomatis deoxyribonucleic acid from urethral samples was purified and submitted to real time polymerase chain reaction to identify the presence of C. trachomatis. RESULTS: A total of 276 human immunodeficiency virus-infected men were included in the study. The prevalence of C. trachomatis infection was 12% (95% confidence interval 8.1%-15.7%). The mean age of the participants was 34.63 (standard deviation 10.80) years. Of the 276 human immunodeficiency virus-infected men, 93 (56.2%) had more than one sexual partner in the past year and 105 (38.0%) reported having their first sexual intercourse under the age of 15 years. Men having sex with men and bisexuals amounted to 61.2% of the studied population. A total of 71.7% had received human immunodeficiency virus diagnosis in the last three years and 55.1% were using antiretroviral therapy. Factors associated with C. trachomatis infection in the logistic model were being single (p<0.034), men having sex with men (p<0.021), and having previous sexually transmitted diseases (p<0.001). CONCLUSION: The high prevalence of C. trachomatis infection among human immunodeficiency virus-infected men highlights that screening human immunodeficiency virus-infected men for C. trachomatis, especially among men having sex with men, is paramount to control the spread of C. trachomatis infection. PMID- 24216157 TI - No surprise in the first Born approximation for electron scattering. AB - In a recent article it is argued that the far-field expansion of electron scattering, a pillar of electron diffraction theory, is wrong (Treacy and Van Dyck, 2012). It is further argued that in the first Born approximation of electron scattering the intensity of the electron wave is not conserved to first order in the scattering potential. Thus a "mystery of the missing phase" is investigated, and the supposed flaw in scattering theory is seeked to be resolved by postulating a standing spherical electron wave (Treacy and Van Dyck, 2012). In this work we show, however, that these theses are wrong. A review of the essential parts of scattering theory with careful checks of the underlying assumptions and limitations for high-energy electron scattering yields: (1) the traditional form of the far-field expansion, comprising a propagating spherical wave, is correct; (2) there is no room for a missing phase; (3) in the first Born approximation the intensity of the scattered wave is conserved to first order in the scattering potential. The various features of high-energy electron scattering are illustrated by wave-mechanical calculations for an explicit target model, a Gaussian phase object, and for a Si atom, considering the geometric conditions in high-resolution transmission electron microscopy. PMID- 24216158 TI - Maternal mortality due to pandemic influenza A H1N1 2009 virus in Colombia. AB - AIMS: The 2009 H1N1 pandemic illustrated the higher morbidity and mortality from viral infections in peripartum women. We describe clinical features of women who recently died of H1N1 in Colombia. METHODS: This is a case series study that was gathered through a retrospective record review of all maternal H1N1 deaths in the country. The national mortality database of confirmed mortality from H1N1 in pregnancy and up to 42 days after delivery was reviewed during the H1N1 season in 2009. Women with H1N1 infections were confirmed by the laboratory of virology. Demographic, clinical, and laboratory data were reviewed. Statistical analyses were performed and median values of non-parametric data were reported with inter quartile range (IQR). RESULTS: A total of 23 H1N1 maternal deaths were identified. Eighty-three percent occurred in the third trimester. None of the mothers who died had received influenza vaccination. The median time from symptom onset to the initiation of antiviral treatment was 8.8 days (IQR 5.8-9.8). Five fatalities did not receive any anti-viral therapy. Median PaO2/FiO2 on day 1 was 80 (IQR, 60-98.5). All patients required inotropic support and mechanical ventilation with barotrauma-related complications of mechanical ventilation occurring in 35% of patients. CONCLUSION: In Colombia, none of the women suffering H1N1-related maternal deaths had received vaccination against the disease and most had delayed or had no anti-viral therapy. Given the lack of evidence-based clinical predictors to identify women who are prone to die from H1N1 in pregnancy, following international guidelines for vaccination and initiation of antiviral therapy in suspected cases would likely improve outcomes in developing countries. PMID- 24216159 TI - Evaluation of the role of first-trimester obstetric ultrasound in the detection of major anomalies: a systematic review. AB - AIM: To perform a systematic review to assess the accuracy of first-trimester ultrasound (US) in the diagnoses of major structural malformations in chromosomally normal fetuses. METHODS: References were obtained from the MEDLINE database, without time range limitations. For each, the risk of bias was evaluated and the important data were extracted. Only studies that used first trimester US to diagnose major structural malformations were included. We evaluated the sensitivity of US over a low-risk unselected population of pregnant women carrying euploid fetuses. RESULTS: A total of 19 studies were included, contributing to 126,937 fetuses and 1399 major malformations. The prevalence of lethal and severe malformations obtained was 1.2% [95% confidence interval (CI), 1.0-1.4]. Both averaged and pooled sensitivity, 50.0% (95% CI 44.1-55.9) and 45.2%, respectively, presented a moderate value for first-trimester US in the detection of structural malformations. CONCLUSION: Based on our analysis of the data, the average sensitivity of first-trimester US to detect structural malformations was 50%. It is our conviction that US has the potential to evolve in this role by exploiting the natural history of malformations and the development of US techniques. PMID- 24216161 TI - Reply to: Ismail AQT, Lahiri S. Management of prelabor rupture of membranes (PROM) at term. J Perinat Med. 2013. PMID- 24216162 TI - Application of microbiological quantitative methods for evaluation of changes in the amount of bacteria in patients with wounds and purulent fistulas subjected to phage therapy and for assessment of phage preparation effectiveness (in vitro studies). AB - PURPOSE: Quantitative microbiological studies may provide important information required for successful phage therapy (PT), however methods for PT monitoring of purulent wounds and fistulas has never been reported before. Therefore our goal was to determine and apply microbiological quantitative methods (MQMs) for monitoring experimental PT. METHODS: Samples from agar plates with growing bacteria were collected using dry and wet sterile compresses, or swabs. After shaking the sample in saline the amount of bacteria in suspension was determined. The method was standardized. The MQM using compress was applied for comparison of in vitro activity of phage preparations with other agents for wound rinsing. The usefulness of this swabbing method was tested in the Phage Therapy Unit for monitoring of experimental PT of patients with chronic wounds or purulent fistulas. RESULTS: Minimum, maximum and standard deviation values used for standardization of the studied method showed that data repeatability was good; thus the method was used for quantitation of bacteria taken both from plates in vitro and patients samples. Effectiveness of phage preparations was compared to gentamicin in vitro. Phages were as effective as antibiotics in reducing the amount of bacteria on agar plates, and this effect was not only due to simple mechanical removal of bacteria, but dependent on their antibacterial activity. We have also observed that the results of bacteria quantitation may correlate with the local status of a wound/fistula in a particular stage of PT. CONCLUSION: The standardized swabbing method of bacteria quantitation can be used for PT monitoring. Presented MQMs are simple and may help to monitor the therapy process and to decide on its duration, frequency and a kind of the phage applied. They can also be applied in other antibacterial treatment strategies. PMID- 24216160 TI - Psychosocial stress in pregnancy and preterm birth: associations and mechanisms. AB - AIMS: Psychosocial stress during pregnancy (PSP) is a risk factor of growing interest in the etiology of preterm birth (PTB). This literature review assesses the published evidence concerning the association between PSP and PTB, highlighting established and hypothesized physiological pathways mediating this association. METHOD: The PubMed and Web of Science databases were searched using the keywords "psychosocial stress", "pregnancy", "pregnancy stress", "preterm", "preterm birth", "gestational age", "anxiety", and "social support". After applying the exclusion criteria, the search produced 107 articles. RESULTS: The association of PSP with PTB varied according to the dimensions and timing of PSP. Stronger associations were generally found in early pregnancy, and most studies demonstrating positive results found moderate effect sizes, with risk ratios between 1.2 and 2.1. Subjective perception of stress and pregnancy-related anxiety appeared to be the stress measures most closely associated with PTB. Potential physiological pathways identified included behavioral, infectious, neuroinflammatory, and neuroendocrine mechanisms. CONCLUSIONS: Future research should examine the biological pathways of these different psychosocial stress dimensions and at multiple time points across pregnancy. Culture-independent characterization of the vaginal microbiome and noninvasive monitoring of cholinergic activity represent two exciting frontiers in this research. PMID- 24216163 TI - Immunosuppressive activity of an aqueous Viola tricolor herbal extract. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Heartsease (Viola tricolor L.), a member of the Violaceae family, has a long history as a medicinal plant and has been documented in the Pharmacopoeia of Europe. Due to its anti-inflammatory properties it is regarded as a traditional remedy against skin diseases, for example for the treatment of scabs, itching, ulcers, eczema or psoriasis, and it is also used in the treatment of inflammation of the lungs and chest such as bronchitis or asthma. Because T-cells play an important role in the pathological process of inflammatory diseases we investigated the effect of an aqueous Viola extract on lymphocyte functions and explored the 'active' principle of the extract using bioactivity-guided fractionation. MATERIAL AND METHODS: An aqueous Viola extract was prepared by C18 solid-phase extraction. Effects on proliferation of activated lymphocytes (using the cell membrane permeable fluorescein dye CFSE), apoptosis and necrosis (using annexin V and propidium iodide staining), interleukin-2 (IL 2) receptor expression (using fluorochrome-conjugated antibodies) and IL-2 cytokine secretion (using an ELISA-based bead array system) were measured by flow cytometry. Influence on lymphocyte polyfunctionality was characterized by Viola extract-induced production of IFN-gamma and TNF-alpha, as well as its influence on lymphocyte degranulation activity. Fractionation and phytochemical analysis of the extract were performed by RP-HPLC and mass spectrometry. RESULTS: The aqueous Viola extract inhibited proliferation of activated lymphocytes by reducing IL-2 cytokine secretion without affecting IL-2 receptor expression. Similarly, effector functions were affected as indicated by the reduction of IFN-gamma and TNF-alpha production; degranulation capacity of activated lymphocytes remained unaffected. Bioassay-guided fractionation and phytochemical analysis of the extract led to identification of circular plant peptides, so called cyclotides, as bioactive components. CONCLUSION: An aqueous Viola extract contains bioactive cyclotides, which inhibit proliferation of activated lymphocytes in an IL-2 dependent manner. The findings provide a rationale for use of herbal Viola preparations in the therapy of disorders related to an overactive immune system. However, further studies to evaluate its clinical potency and potential risks have to be performed. PMID- 24216164 TI - Pharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC/MS/MS. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Aucklandiae (RA), a well known traditional Chinese medicine, is widely used for treating various problems in digestive system. A selective and sensitive high-performance liquid chromatography coupled with mass spectrometry method was first developed and validated for simultaneous quantification of costunolide and dehydrocostuslactone in rat plasma with diazepam as internal standard after oral administration of RA extraction. MATERIALS AND METHODS: Plasma samples were extracted via solid-phase extraction and detected by multiple-reaction monitoring mode under positive electrospray. Chromatographic separation was accomplished on an Agilent C18 column (2.1 mm * 150 mm, 5 um), with 0.1% formic acid and acetonitrile (1:1) as the mobile phase at a flow rate of 0.5 mL/min. RESULTS: The quantification was performed using the transitions of m/z 233/187 for costunolide, m/z 231/185 for dehydrocostuslactone and m/z 285/193 for diazepam, respectively. Calibration curves were linear over the concentration range of 0.7-769.7 ng/mL for costunolide and 0.9-956.0 ng/mL for dehydrocostuslactone. The intra-day and inter-day precisions (RSD%) for two compounds was less than 8.76% and 9.70% and the accuracy (RE%) range from 6.14% to 5.35%. The time to reach the maximum plasma concentration (Tmax) was 10.46 h for costunolide, 12.39 h dehydrocostuslactone. The elimination half-time (t1/2) of costunolide and dehydrocostuslactone was 5.54 +/- 0.81 and 4.32 +/- 0.71 (h). The AUC of costunolide and dehydrocostuslactone was 308.83 and 7884.51 respectively (ngh/mL). CONCLUSIONS: It was the first report for the study of pharmacokinetic profile of costunolide and dehydrocostuslactone in rat plasma after oral administration of RA extract. These results provided a meaningful basis for better understanding the absorption of traditional medicine, RA, and provide useful scientific data for clinical application. PMID- 24216165 TI - Safety and toxicity issues associated with lead-based traditional herbo-metallic preparations. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herbal and herbo-mineral preparations are being traditionally used in Indian medicines. The herbo-mineral preparations have several benefits that have been instrumental in their widespread use in treatment of different disorders by traditional medicinal practitioners. These include better stability, lower dosage, ease of storability and sustained availability. Naga bhasma (lead sulphide ash), a traditional Indian herbo-mineral medication prepared using lead and several herbal ingredients, has been used as an oral medicine in India for many years for the treatment of diabetes, spleen enlargement, diarrhoea and various skin diseases. The elaborate preparation protocol involved in the traditional medicines is believed to modify the toxic nature of the precursor (metal) and adds therapeutic value. But modern scientists claim that these preparations are toxic to health as they contain large amount of metal. Many factors such as preparation based factors, chemical nature based factors, vehicle used, therapy associated factors, pharmacological factors, etc, determine whether the traditional medicines are toxic or not. This review focuses on the safety and critical issues associated with Naga bhasma-a lead based ayurvedic medicine. MATERIALS AND METHODS: The detailed review of literature about Naga bhasma apart from other lead based formulations are carried out by utilizing the resources including, classical Indian text books, databases such as Pub med, Scopus, Science direct and few other web sources. RESULTS: Though metallic lead is known to be toxic to the biological system, no compelling evidence has been put forth to suggest any toxic manifestations of Naga bhasma. The elemental characterization of preparations containing Naga bhasma has shown extremely high levels of lead content and various parameters must be taken into consideration in deciding the safety and critical issues present in traditional medicines. As there are no molecular targets available for most of the traditional medicine, it is difficult to assure the safety in using this traditional preparation. Highly intensive research encompassing physico-chemical, engineering as well as biological aspects need to be carried out to understand the applicability of such preparations in a modern context. CONCLUSION: As there are no molecular targets available for most of the traditional medicine, it is difficult to assure the safety in using this traditional preparation. Highly intensive research encompassing physico-chemical, engineering as well as biological aspects need to be carried out to understand the applicability of such preparations in a modern context. PMID- 24216166 TI - Single-agent obatoclax (GX15-070) potently induces apoptosis and pro-survival autophagy in head and neck squamous cell carcinoma cells. AB - OBJECTIVES: More than half of head and neck squamous cell carcinoma (HNSCC) patients are initially treated with curative intent, but will relapse over the course of their disease and have poor prognosis with a median survival of approximately 6months. Novel therapeutic approaches are in desperate need for this patient population. The anti-apoptotic BCL-2 family proteins such as BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a small-molecule antagonist of the BH3 binding groove of anti-apoptotic BCL-2 family. We evaluated the activity of obatoclax against 4 HNSCC cell lines (UMSCC-1, Cal33, 1483, UMSCC-22A). METHODS: Cell viability was determined by MTT assay, cell cycle status by propidium iodide staining, and apoptosis by Annexin-V staining and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting. RESULTS: All four HNSCC cell lines were highly sensitive to single-agent obatoclax with IC50's ranging from 46 to 177nM. Obatoclax induced apoptosis in all four HNSCC cell lines as evidenced by increases in sub-G1 DNA content, Annexin-V staining, and PARP cleavage. In addition, obatoclax induced autophagy in all 4 cell lines, and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity. CONCLUSION: Our findings demonstrate potent monotherapeutic activity of obatoclax against HNSCC cells, and enhancement of this activity in the presence of chloroquine. This preclinical study suggests that obatoclax might have therapeutic value in the treatment of HNSCC, either alone or in combination with inhibitors of autophagy. PMID- 24216167 TI - A brief review of 50 years of perioperative thrombosis and hemostasis management. AB - Perioperative thrombosis and hemostasis management has changed dramatically over the past 50 years. From two anticoagulants and one anti-aggregant, the number of currently available drugs has recently increased several-fold, leaving clinicians with the problem of choosing the optimal agent. Individualized preoperative assessment of bleeding risk based on bleeding history and testing limited to high risk patients is an emerging concept. Based on the identification of risk factors for venous thromboembolism (VTE), pharmacologic and non-pharmacologic strategies for perioperative VTE prophylaxis have had a major impact on patient outcome. For patients undergoing surgery who are treated with anticoagulants and anti aggregants, "bridging" strategies have been proposed. Bleeding management strategies have shifted focus from replacing lost blood volume to new approaches aimed at preventing blood loss, reducing the potential complications of blood loss, and preventing the transfusion of blood products. For some areas of perioperative thrombosis and hemostasis management, randomized controlled trial (RCT) data are emerging, but the database remains insufficient to date. Clearly, more RCTs need to be published for perioperative thrombosis and hemostasis management to become an evidence-based approach. PMID- 24216168 TI - Mouse medicine and human biology. PMID- 24216169 TI - Modeling human hematopoietic stem cell biology in the mouse. AB - Hematopoietic stem cells (HSCs) have the immense task of supplying an organism with enough blood to sustain a lifespan. Much of what is known about how this scant population of cells can meet the varying demand of producing more than 10(11) cells per day comes from studies conducted in an animal that is a fraction of our size and lives roughly 1/30th of our lifespan. The differences in longevity can be expected to impose different demands on a cell essential for existence. It is therefore unsurprising that while the mouse has proven invaluable in defining the organizing principals of how hematopoiesis is governed, mediators of cell localization as well as a range of experimental methods, the differences in cell cycling, DNA repair and specific molecular features of HSCs in humans are evident and important. Here, the utility and drawbacks of the mouse as an experimental model for human HSC biology are discussed. PMID- 24216171 TI - Advances in the development of animal models of myeloid leukemias. AB - The ideal in vivo models for studies of leukemia pathogenesis and treatment would have several important features. First, these animals would have phenotypes that are robust and reproducible. Second, these models would reliably develop phenotypes that accurately recapitulate disease observed in the clinic with short latency and high penetrance sufficient for informative preclinical therapeutic studies. Leukemia models based on retroviral transduction of oncogenes followed by transplantation into irradiated syngeneic hosts offer a rapid and cost efficient way to evaluate the effects of a gene or mutation of interest but in some cases result in inconsistent phenotypes due to non-physiological levels of expression and random genomic integration. Xenotransplantation models enable the propagation and analysis of primary human samples but may be difficult to interpret due to variability of genetic background, the effects of immune recognition, a limited knowledge of genetic alterations in samples before and after xenotransplantation, and incomplete interaction with the microenvironment. Genetically engineered mice represent tractable models of human myeloid malignancies, and in many cases empower the study of the molecular pathogenesis of leukemia and evaluation of novel chemotherapeutics. Our understanding of the molecular pathogenesis of myeloid malignancies relies largely on the knowledge of cytogenetic abnormalities and recurrent chromosomal translocations, many of which have been successfully modeled in laboratory animals. In addition, as our knowledge of the genetics of myeloid leukemia improves with additional integrated profiling efforts, it will lead to more accurate animal models and facilitate translational efforts in the leukemia field. Here we review the most recent advances in the generation of mouse models of myeloid leukemias. PMID- 24216172 TI - Aplastic anemia: what have we learned from animal models and from the clinic. AB - Aplastic anemia (AA) is currently perceived as an immune-mediated disease in which aberrant effector cells recognize and destroy primitive marrow elements, resulting in pancytopenia. The immune hypothesis is based on clinical observations of responsiveness of AA to immunomodulatory agents such as anti thymocyte globulin (ATG) and the requirement of cyclosporine to maintain response; evidence of an immune system in disarray provided by abnormal regulatory, TH1, TH17, and expanded CD8(+) T-cell populations, and animal models of immune-mediated marrow destruction, where many of the observed clinical and in vitro alterations can be confirmed and expanded. Murine models mimicking AA have used exposure to agents that result in marrow destruction through a direct toxic effect, but models that explore antigenic disparities between strains have resulted in immune-mediated destruction of the marrow, more closely modeling human AA. Many experiments in mice have helped confirm and elucidate specific mechanisms of marrow destruction. However, clinical development of regimens in AA has not relied on establishing their success in murine model. Instead, drugs and their combinations investigated in AA were those shown clinically to be active in AA, in other hematologic diseases, or in other specialties such as in rheumatology, and solid and bone marrow transplantation. In this review, the evolution of murine models and their clinical relevance in AA are discussed. PMID- 24216173 TI - Re-assessment of selected Baby-Friendly maternity facilities in Accra, Ghana. AB - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) has been implemented in Ghana since 1995. At the end of 2011, about 325 maternity facilities in Ghana had been designated Baby Friendly. However, none had been re-assessed for adherence to the Ten Steps to successful breastfeeding (Ten Steps). The current study re assessed six maternity facilities in Accra for adherence to the Ten Steps and the International Code of Marketing of breast milk substitutes (the Code). METHODS: Three independent assessors performed the re-assessment using the revised WHO/UNICEF external re-assessment tool (ERT) between April and June, 2011. All sections of the ERT were implemented, except for the HIV/infant feeding section. Assessors interviewed 90 clinical staff of the facilities, 60 pregnant women, and 150 women who had given birth and waiting to be discharged from the hospital. Additionally, observations were completed on neonate feeding and compliance with the Code. Data was analyzed to assess adherence to the Ten Steps and the Code. RESULTS: In 2010, the six facilities recorded a total of 26,339 deliveries. At discharge, the weighted exclusive breastfeeding rate was 93.8%. None of the facilities adhered completely to the Ten Steps. Overall, the rate of adherence to the Ten Steps was 42% (range = 30 - 70%). No facility met the criteria for Steps One and Two. Only Step Seven was adhered to by all facilities. Overall compliance with the Code was about 54%. Trained staff attrition, high client-staff ratios, inadequate in-service training for new staff, and inadequate support for regional and national program monitoring were identified as barriers to adherence. CONCLUSION: Poor adherence to Baby-Friendly practices in designated BFHI facilities was observed in urban Accra. Renewed efforts to support monitoring of designated facilities is recommended. PMID- 24216170 TI - Mouse models in bone marrow transplantation and adoptive cellular therapy. AB - Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID- 24216174 TI - Regulatory B cells: the new "it" cell. AB - Regulatory B cells (Breg) are a subpopulation of B cells that play a suppressive role in the immune system. The mechanism of how these immune cells perform their effects has been explored by experiments in mice and in humans. Intracellular staining for interleukin 10 continues to be a consistent and reproducible method of identifying Breg in mouse and human studies. The lack of Breg is associated with a worsening of several autoimmune diseases such as collagen-induced arthritis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis in murine studies. The purpose of this review is to provide a concise summary of the role of Breg in the immune system, including the most recently studied cell surface markers associated with Breg, and to describe the role of Breg in the etiology of several autoimmune diseases, the current understanding of Breg development, their role in the development of autoimmune diseases, and their role in inducing tolerance after transplantation. PMID- 24216175 TI - A more than 20% increase in deceased-donor organ procurement and transplantation activity after the use of donation after circulatory death. AB - BACKGROUND: Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS: Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS: There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors >=60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS: This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source. PMID- 24216176 TI - MicroRNAs in T helper cell differentiation and plasticity. AB - Understanding how T cells generate productive and long-lasting responses, and how these mechanisms are dysregulated in autoimmune and inflammatory disorders is crucial for prevention and treatment of these diseases. MicroRNAs (miRNAs) are short noncoding RNA species able to suppress gene expression post transcriptionally. Hundreds of different miRNAs are produced in a cell starting from longer precursors. While the role of miRNAs has been clearly established in the regulation of the differentiation, proliferation and effector functions of a variety of immune cells, here I will focus specifically on miRNAs known to be involved in regulating the biology of CD4 T helper lymphocytes. PMID- 24216178 TI - Prevalence of intra-abdominal hypertension (IAH) among patients with severe burns. PMID- 24216179 TI - Tinbergen's four questions, organized: a response to Bateson and Laland. PMID- 24216177 TI - Neural circuits with long-distance axon tracts for determining functional connectivity. AB - The cortical circuitry in the brain consists of structurally and functionally distinct neuronal assemblies with reciprocal axon connections. To generate cell culture-based systems that emulate axon tract systems of an in vivo neural network, we developed a living neural circuit consisting of compartmentalized neuronal populations connected by arrays of two millimeter-long axon tracts that are integrated on a planar multi-electrode array (MEA). The millimeter-scale node to-node separation allows for pharmacological and electrophysiological manipulations to simultaneously target multiple neuronal populations. The results show controlled selectivity of dye absorption by neurons in different compartments. MEA-transmitted electrical stimulation of targeted neurons shows ~46% increase of intracellular calcium levels with 20 Hz stimulation, but ~22% decrease with 2k Hz stimulation. The unique feature of long distance axons promotes in vivo-like fasciculation. These axon tracts are determined to be inhibitory afferents by showing increased action potential firing of downstream node upon selective application of gamma-aminobutyric acid (GABA) to the upstream node. Together, this model demonstrates integrated capabilities for assessing multiple endpoints including axon tract tracing, calcium influx, network architecture and activities. This system can be used as a multi-functional platform for studying axon tract-associated CNS disorders in vitro, such as diffuse axonal injury after brain trauma. PMID- 24216180 TI - A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. AB - We have recently gained a remarkable understanding of the mutational landscape of head and neck squamous cell carcinoma (HNSCC). However, the nature of the dysregulated signaling networks contributing to HNSCC progression is still poorly defined. Here, we have focused on the role of the family of mitogen activated kinases (MAPKs), extracellular regulated kinase (ERK), c-Jun terminal kinase (JNK) and p38 MAPK in HNSCC. Immunohistochemical analysis of a large collection of human HNSCC tissues revealed that the levels of the phosphorylated active form of ERK1/2 and JNK were elevated in less than 33% and 16% of the cases, respectively. Strikingly, however, high levels of active phospho-p38 were observed in most (79%) of hundreds of tissues analyzed. We explored the biological role of p38 in HNSCC cell lines using three independent approaches: treatment with a specific p38 inhibitor, SB203580; a retro-inhibition strategy consisting in the use of SB203580 combined with the expression of an inhibitor insensitive mutant form of p38alpha; and short-hairpin RNAs (shRNAs) targeting p38alpha. We found that specific blockade of p38 signaling significantly inhibited the proliferation of HNSCC cells both in vitro and in vivo. Indeed, we observed that p38 inhibition in HNSCC cancer cells reduces cancer growth in tumor xenografts and a remarkable decrease in intratumoral blood and lymphatic vessels. We conclude that p38alpha functions as a positive regulator of HNSCC in the context of the tumor microenvironment, controlling cancer cell growth as well as tumor-induced angiogenesis and lymphangiogenesis. PMID- 24216181 TI - Diagnostic accuracy of three scoring methods for the Davidson Trauma Scale among U.S. military veterans. AB - Self-report questionnaires are frequently used to identify PTSD among U.S. military personnel and Veterans. Two common scoring methods used to classify PTSD include: (1) a cut score threshold and (2) endorsement of PTSD symptoms meeting DSM-IV-TR symptom cluster criteria (SCM). A third method requiring a cut score in addition to SCM has been proposed, but has received little study. The current study examined the diagnostic accuracy of three scoring methods for the Davidson Trauma Scale (DTS) among 804 Afghanistan and Iraq war-era military Service Members and Veterans. Data were weighted to approximate the prevalence of PTSD and other Axis I disorders in VA primary care. As expected, adding a cut score criterion to SCM improved specificity and positive predictive power. However, a cut score of 68-72 provided optimal diagnostic accuracy. The utility of the DTS, the role of baseline prevalence, and recommendations for future research are discussed. PMID- 24216182 TI - Mesenchymal stem cells versus mesenchymal stem cells combined with cord blood for engraftment failure after autologous hematopoietic stem cell transplantation: a pilot prospective, open-label, randomized trial. AB - Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% +/- 12.0%, 79.5% +/- 9.4%, and 20.5% +/- 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction. PMID- 24216183 TI - CMV and relapse: what has conditioning to do with it? PMID- 24216184 TI - Long-term outcomes of alemtuzumab-based reduced-intensity conditioned hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myelogenous leukemia secondary to myelodysplastic syndrome. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted. PMID- 24216185 TI - Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. AB - Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 * 10(6) hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at day +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after hMSC infusion. Patients who responded to therapy by day +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; P < .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation. PMID- 24216186 TI - Validity and reliability of a novel written examination to assess knowledge and clinical decision making skills of medical students on the surgery clerkship. AB - BACKGROUND: The Surgery Clerkship Clinical Skills Examination (CSE) is a novel written examination developed to assess the surgical knowledge, clinical decision making, communication skills, and professionalism of medical students on the surgery clerkship. This study was undertaken to determine its validity. METHODS: Data were prospectively collected from July 2011 through February 2013. Multivariate linear and logistic regression analyses were used to assess score trend; convergent validity with National Board of Medical Examiners surgery and medicine subject scores, United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge scores, and evaluation of clinical reasoning and fund of knowledge; and the effect of clerkship order. Exam reliability was assessed using a modified Cronbach's alpha statistic. RESULTS: During the study period, 262 students completed the CSE, with a normal distribution of performance. United States Medical Licensing Examination Step 2 Clinical Knowledge score and end-of clerkship evaluations of fund of knowledge and clinical reasoning predicted CSE score. Performance on the CSE was independent of clerkship order or prior clerkships. The modified Cronbach's alpha value for the exam was .67. CONCLUSIONS: The CSE is an objective, valid, reliable instrument for assessing students on the surgery clerkship, independent of clerkship order. PMID- 24216187 TI - Do more with less: a surgery directed institutional model for resident central line training. AB - BACKGROUND: Simulation training can improve proficiency in central line placement, but it is expensive and resource intensive. The authors developed a 3 phase approach to central venous catheter placement training, including an online module, mannequin-based simulation using a single faculty member, followed by department directed clinical observation. The hypothesis was that standardizing institutional central venous catheter placement training would maintain training efficiency and reduce faculty and resource demands. METHODS: Preintervention and postintervention assessments of the trainees' performance were collected to evaluate program effectiveness. Program surveys were collected to evaluate residents' satisfaction and comfort with the procedure. Resource utilization was compared between the period before program implementation and the 2 following years. RESULTS: Mean pretest to posttest scores for the online module improved significantly from 7.0 to 8.4 in 2010 and from 7.1 to 8.4 in 2011. Video evaluation demonstrated significant improvement across all postgraduate year levels. Surveys revealed high resident satisfaction and increased procedural confidence. Overall resource costs and faculty requirements decreased. CONCLUSIONS: A standardized training program for an entire institution can maintain quality while being more cost effective than traditional central venous catheter placement training. PMID- 24216188 TI - Hand motion patterns of Fundamentals of Laparoscopic Surgery certified and noncertified surgeons. AB - BACKGROUND: With the increasing use of simulation in surgical training there is an increasing need for low cost methods of objective assessment. METHODS: Hand motion data (3 degrees of freedom) were acquired using microelectromechanical gyroscope tracking devices worn on both hands during an intracorporeal suture/knot-tying laparoscopic task performed by FLS-certified and non-FLS certified surgeons. Each data sample was processed into a symbolic time series, and the Lempel-Ziv complexity metric was calculated for each hand for the whole task and the first 60 seconds of the task from the dominant hand. RESULTS: FLS certified surgeons had more complex hand-motion patterns. This was statistically significant only for the dominant hand (P = .02) but was still statistically significant when calculated from the first 60 seconds of the task (P = .04) and therefore independent of the total time taken to complete the task. CONCLUSIONS: Hand-motion patterns were quantified and shown to be different between FLS certified and non-FLS-certified surgeons using low-cost microelectromechanical technology and the Lempel-Ziv complexity metric. PMID- 24216190 TI - Patient involvement in quality improvement: is it time we let children, young people and families take the lead? AB - It is vital to involve children, young people and families in the design, delivery and improvement of their care. Their involvement can range from individuals giving feedback, such as patient stories, to collaborative work including patient groups and communities helping to develop and commission services. The methods for involving individuals and families include questionnaires and innovative ideas such as feedback Apps. Other methods include the 15 Steps Challenge which helps an organisation to view the care it delivers through a patients eyes and includes a 'walk around' involving a patient, carer, staff member and board member. The Experience Based Design approach is another method of reviewing a service and involves assessing how staff and patients feel when delivering and receiving care. Involving patient groups can be facilitated by working with schools and children's centres. The type of involvement will vary, but if carefully designed can allow meaningful participation and improvement of services. PMID- 24216191 TI - Biodiversity, conservation biology, and rational choice. AB - This paper critically discusses two areas of Sahotra Sarkar's recent work in environmental philosophy: biodiversity and conservation biology and roles for decision theory in incorporating values explicitly in the environmental policy process. I argue that Sarkar's emphasis on the practices of conservation biologists, and especially the role of social and cultural values in the choice of biodiversity constituents, restricts his conception of biodiversity to particular practical conservation contexts. I argue that life scientists have many reasons to measure many types of diversity, and that biodiversity metrics could be value-free. I argue that Sarkar's emphasis on the limitations of normative decision theory is in tension with his statement that decision theory can "put science and ethics together." I also challenge his claim that multi criteria decision tools lacking axiomatic foundations in preference and utility theory are "without a rational basis," by presenting a case of a simple "outranking" multi-criteria decision rule that can violate a basic normative requirement of preferences (transitivity) and ask whether there may nevertheless be contexts in which such a procedure might assist decision makers. PMID- 24216192 TI - This issue features research presented at the 20th RACI Research and Development Topics Conference in Analytical and Environ-mental Chemistry (11th-14th December 2012, Deakin University, Geelong, Australia). Foreword. PMID- 24216193 TI - Applications of resistive heating in gas chromatography: a review. AB - Gas chromatography is widely applied to separate, identify, and quantify components of samples in a timely manner. Increasing demand for analytical throughput, instrument portability, environmental sustainability, and more economical analysis necessitates the development of new gas chromatography instrumentation. The applications of resistive column heating technologies have been espoused for nearly thirty years and resistively heated gas chromatography has been commercially available for the last ten years. Despite this lengthy period of existence, resistively heated gas chromatography has not been universally adopted. This low rate of adoption may be partially ascribed to the saturation of the market with older convection oven technology, coupled with other analytical challenges such as sampling, injection, detection and data processing occupying research. This article assesses the advantages and applications of resistive heating in gas chromatography and discusses practical considerations associated with adoption of this technology. PMID- 24216195 TI - Phosphomolybdate-doped-poly(3,4-ethylenedioxythiophene) coated gold nanoparticles: synthesis, characterization and electrocatalytic reduction of bromate. AB - Phosphomolybdate, H3PMo12O40, (PMo12)-doped-poly(3,4-ethylenedioxythiophene) (PEDOT) coated gold nanoparticles have been synthesized in aqueous solution by reduction of AuCl4(-) using hydroxymethyl EDOT as a reducing agent in the presence of polystyrene sulfonate and PMo12. The resulting PMo12-doped-PEDOT stabilized Au nanoparticles are water soluble and have been characterized by UV visible spectroscopy, scanning electron microscopy and electrochemistry. Glassy carbon electrodes modified with these Au nanoparticles show excellent stability and catalytic activity towards the reduction of bromate in an aqueous electrolyte solution containing 10mM H2SO4 and 0.1M Na2SO4. PMID- 24216194 TI - Flow injection analysis as a tool for enhancing oceanographic nutrient measurements--a review. AB - Macronutrient elements (C, N and P) and micronutrient elements (Fe, Co, Cu, Zn and Mn) are widely measured in their various physico-chemical forms in open ocean, shelf sea, coastal and estuarine waters. These measurements help to elucidate the biogeochemical cycling of these elements in marine waters and highlight the ecological and socio-economic importance of the oceans. Due to the dynamic nature of marine waters in terms of chemical, biological and physical processes, it is advantageous to make these measurements in situ and in this regard flow injection analysis (FIA) provides a suitable shipboard platform. This review, therefore, discusses the role of FIA in the determination of macro- and micro-nutrient elements, with an emphasis on manifold design and detection strategies for the reliable shipboard determination of specific nutrient species. The application of various FIA manifolds to oceanographic nutrient determinations is discussed, with an emphasis on sensitivity, selectivity, high throughput analysis and suitability for underway analysis and depth profiles. Strategies for enhancing sensitivity and minimizing matrix effects, e.g. refractive index (schlieren) effects and the important role of uncertainty budgets in underpinning method validation and data quality are discussed in some detail. PMID- 24216196 TI - Electrochemical and microfabrication strategies for remotely operated smart chemical sensors: application of anodic stripping coulometry to calibration-free measurements of copper and mercury. AB - Remote unattended sensor networks are increasingly sought after to monitor the drinking water distribution grid, industrial wastewater effluents, and even rivers and lakes. One of the biggest challenges for application of such sensors is the issue of in-field device calibration. With this challenge in mind, we report here the use of anodic stripping coulometry (ASC) as the basis of a calibration-free micro-fabricated electrochemical sensor (CF-MES) for heavy metal determinations. The sensor platform consisted of a photo-lithographically patterned gold working electrode on SiO2 substrate, which was housed within a custom stopped-flow thin-layer cell, with a total volume of 2-4 MUL. The behavior of this platform was characterized by fluorescent particle microscopy and electrochemical studies utilizing Fe(CN)6(3-/4-) as a model analyte. The average charge obtained for oxidation of 500 MUM ferrocyanide after 60s over a 10 month period was 176 MUC, corresponding to a volume of 3.65 MUL (RSD = 2.4%). The response of the platform to copper concentrations ranging from 50 to 7500 ppb was evaluated, and the ASC results showed a linear dependence of charge on copper concentrations with excellent reproducibility (RSD <= 2.5%) and accuracy for most concentrations (<= 5-10% error). The platform was also used to determine copper and mercury mixtures, where the total metallic content was measurable with excellent reproducibility (RSD <= 4%) and accuracy (<= 6% error). PMID- 24216197 TI - An evaluation of ferrihydrite- and MetsorbTM-DGT techniques for measuring oxyanion species (As, Se, V, P): effective capacity, competition and diffusion coefficients. AB - This study investigated several knowledge gaps with respect to the diffusive gradients in thin films (DGT) technique for measurement of oxyanions (As(III), As(V), Se(IV), Se(VI), PO4(3-), and V(V)) using the ferrihydrite and MetsorbTM binding layers. Elution efficiencies for each binding layer were higher with 1:20 dilutions, as analytical interferences for ICP-MS were minimised. Diffusion coefficients measured by diffusion cell and by DGT time-series experiments were found to agree well and generally agreed with previously reported values, although a range of diffusion coefficients have been reported for inorganic As and Se species. The relative binding affinity for both ferrihydrite and MetsorbTM was PO4(3-) ~ As(V)>V(V) ~ As(III)>Se(IV) >>> Se(VI) and effective binding capacities were measured in single ion solutions, and spiked synthetic freshwater and seawater, advising practical decisions about DGT monitoring. Under the conditions tested the performance of both ferrihydrite and MetsorbTM binding layers was directly comparable for As(V), As(III) Se(IV), V(V) and PO4(3-) over a deployment spanning <= 2 days for both freshwater and seawater. In order to return quantitative data for several analytes we recommend that the DGT method using either ferrihydrite or MetsorbTM be deployed for a maximum of 2 days in marine waters likely to contain high levels of the most strongly adsorbing oxyanions contaminants. The high pH, the competitive ions present in seawater and the identity of co-adsorbing ions affect the capacity of each binding layer for the analytes of interest. In freshwaters, longer deployment times can be considered but the concentration and identity of co-adsorbing ions may impact on quantitative uptake of Se(IV). This study found ferrihydrite-DGT outperformed Metsorb-DGT while previous studies have found the opposite, with variation in binding materials masses used being a likely reason. Clearly, preparation of both binding layers should always be optimised to produce the highest capacity possible, especially for seawater deployments. PMID- 24216198 TI - Silica-based ionic liquid coating for 96-blade system for extraction of aminoacids from complex matrixes. AB - 1-Vinyl-3-octadecylimidazolium bromide ionic liquid [C18VIm]Br was prepared and used for the modification of mercaptopropyl-functionalized silica (Si-MPS) through surface radical chain-transfer addition. The synthesized octadecylimidazolium-modified silica (SiImC18) was characterized by thermogravimetric analysis (TGA), infrared spectroscopy (IR), (13)C NMR and (29)Si NMR spectroscopy and used as an extraction phase for the automated 96 blade solid phase microextraction (SPME) system with thin-film geometry using polyacrylonitrile (PAN) glue. The new proposed extraction phase was applied for extraction of aminoacids from grape pulp, and LC-MS-MS method was developed for separation of model compounds. Extraction efficiency, reusability, linearity, limit of detection, limit of quantitation and matrix effect were evaluated. The whole process of sample preparation for the proposed method requires 270min for 96 samples simultaneously (60min preconditioning, 90min extraction, 60min desorption and 60min for carryover step) using 96-blade SPME system. Inter-blade and intra-blade reproducibility were in the respective ranges of 5-13 and 3-10% relative standard deviation (RSD) for all model compounds. Limits of detection and quantitation of the proposed SPME-LC-MS/MS system for analysis of analytes were found to range from 0.1 to 1.0 and 0.5 to 3.0MUgL(-1), respectively. Standard addition calibration was applied for quantitative analysis of aminoacids from grape juice and the results were validated with solvent extraction (SE) technique. PMID- 24216199 TI - Solid phase microextraction fills the gap in tissue sampling protocols. AB - Metabolomics and biomarkers discovery are an integral part of bioanalysis. However, untargeted tissue analysis remains as the bottleneck of such studies due to the invasiveness of sample collection, as well as the laborious and time consuming sample preparation protocols. In the current study, technology integrating in vivo sampling, sample preparation and global extraction of metabolites--solid phase microextraction was presented and evaluated during liver and lung transplantation in pig model. Sampling approaches, including selection of the probe, transportation, storage conditions and analyte coverage were discussed. The applicability of the method for metabolomics studies was demonstrated during lung transplantation experiments. PMID- 24216200 TI - The use of a polymer inclusion membrane for separation and preconcentration of orthophosphate in flow analysis. AB - A highly sensitive flow analysis system has been developed for the trace determination of reactive phosphate in natural waters, which uses a polymer inclusion membrane (PIM) with Aliquat 336 as the carrier for on-line analyte separation and preconcentration. The system operates under flow injection (FI) and continuous flow (CF) conditions. Under optimal FI conditions the system is characterised by a linear concentration range between 0.5 and 1000 MUg L(-1)P, a sampling rate of 10h(-1), a limit of detection of 0.5 MUgL(-1)P and RSDs of 3.2% (n = 10, 100 MUg L(-1)) and 7.7% (n = 10, 10 MUg L(-1)). Under CF conditions with 10 min stop-flow time and sample solution flow rate of 1.32 mL min(-1) the flow system offers a limit of detection of 0.04 MUg L(-1)P, a sampling rate of 5h(-1) and an RSD of 3.4% (n=5, 2.0 MUg L(-1)). Interference studies revealed that anions commonly found in natural waters did not interfere when in excess of at least one order of magnitude. The flow system, operating under CF conditions, was successfully applied to the analysis of natural water samples containing concentrations of phosphate in the low MUg L(-1)P range, using the multipoint standard addition method. PMID- 24216201 TI - Analysis of organic aerosols collected on filters by Aerosol Mass Spectrometry for source identification. AB - Aerosol Mass Spectrometers (AMS) are powerful tools in the analysis of the chemical composition of airborne particles, particularly organic aerosols which are gaining increasing attention. However, the advantages of AMS in providing on line data can be outweighed by the difficulties involved in its use in field measurements at multiple sites. In contrast to the on-line measurement by AMS, a method which involves sample collection on filters followed by subsequent analysis by AMS could significantly broaden the scope of AMS application. We report the application of such an approach to field studies at multiple sites. An AMS was deployed at 5 urban schools to determine the sources of the organic aerosols at the schools directly. PM1 aerosols were also collected on filters at these and 20 other urban schools. The filters were extracted with water and the extract run through a nebulizer to generate the aerosols, which were analyzed by an AMS. The mass spectra from the samples collected on filters at the 5 schools were found to have excellent correlations with those obtained directly by AMS, with r(2) ranging from 0.89 to 0.98. Filter recoveries varied between the schools from 40 to 115%, possibly indicating that this method provides qualitative rather than quantitative information. The stability of the organic aerosols on Teflon filters was demonstrated by analysing samples stored for up to two years. Application of the procedure to the remaining 20 schools showed that secondary organic aerosols were the main source of aerosols at the majority of the schools. Overall, this procedure provides accurate representation of the mass spectra of ambient organic aerosols and could facilitate rapid data acquisition at multiple sites where AMS could not be deployed for logistical reasons. PMID- 24216202 TI - Liquid-liquid extraction combined with differential isotope dimethylaminophenacyl labeling for improved metabolomic profiling of organic acids. AB - A large fraction of the known human metabolome belong to organic acids. However, comprehensive profiling of the organic acid sub-metabolome is a major analytical challenge. In this work, we report an improved method for detecting organic acid metabolites. This method is based on the use of liquid-liquid extraction (LLE) to selectively extract the organic acids, followed by using differential isotope p dimethylaminophenacyl (DmPA) labeling of the acid metabolites. The (12)C-/(13)C labeled samples are analyzed by liquid chromatography Fourier-transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS). It is shown that this LLE DmPA labeling method offers superior performance over the method of direct DmPA labeling of biofluids such as human urine. LLE of organic acids reduces the interference of amine-containing metabolites that may also react with DmPA. It can also remove water in a biofluid that can reduce the labeling efficiency. Using human urine as an example, it is demonstrated that about 2500 peak pairs or putative metabolites could be detected in a 30-min gradient LC-MS run, which is about 3 times more than that detected in a sample prepared using direct DmPA labeling. About 95% of the 1000 or so matched metabolites to the Human Metabolome Database (HMDB) are organic acids. It is further shown that this method can be used to handle as small as 10 MUL of urine. We believe that this method opens the possibility of generating a very comprehensive profile of the organic acid sub metabolome that will be useful for comparative metabolomics applications for biological studies and disease biomarker discovery. PMID- 24216203 TI - The use of a polymer inclusion membrane in a paper-based sensor for the selective determination of Cu(II). AB - A disposable paper-based sensor (PBS) is described for the determination of Cu(II) in natural and waste waters at approximately 2 cents per measurement. The device makes use of a polymer inclusion membrane (PIM) to provide the selectivity for Cu(II). The PIM consists of 40 wt% di(2-ethlyhexyl) phosphoric acid (D2EHPA) as the carrier, 10 wt% dioctyl phthalate (DOP) as a plasticizer, 49.5 wt% poly(vinyl chloride) (PVC) as the base polymer and 0.5 wt% (mm(-1)) 1-(2' pyridylazo)-2-naphthol (PAN) as the colourimetric reagent. High selectivity under mildly acidic conditions (HCl, pH 2.0) is achieved for Cu(II) in the presence of frequently encountered metal ions in natural and waste waters such as Fe(III), Al(III), Zn(II), Cd(II), Pb(II), Ca(II), Mg(II), and Ni(II). The laminated PBS consists of a PIM sensing disc (2mm in diameter) attached to the centre of a circular hydrophilic zone (7 mm in diameter) pretreated with 0.01 M HCl. This hydrophilic zone separates the sample port (a circular hole in the plastic cover) from the PIM sensing disc. After introducing 19.2 MUL of a sample/standard solution to the sample port, Cu(II) diffuses across the hydrophilic zone and is extracted into the PIM disc as the Cu(II)-D2EHPA complex which subsequently reacts with PAN to produce the red-purple coloured Cu(II)-PAN complex. The colour intensity of the PIM disc is measured 15 min after sample/standard introduction by scanning using a flatbed scanner. Under optimal conditions the device is characterized by a limit of detection (LOD) and limit of quantitation (LOQ) of 0.06 and 0.21 mg L(-1) Cu(II), respectively, with two linear ranges together covering the Cu(II) concentration range from 0.1 to 30.0 mg L(-1). The PBS was successfully applied to the determination of Cu(II) in hot tap water and mine tailings water. PMID- 24216204 TI - Analytical performance of molecular beacons on surface immobilized gold nanoparticles of varying size and density. AB - The high quenching efficiency of metal nanoparticles has facilitated its use as quenchers in molecular beacons. To optimize this system, a good understanding of the many factors that influence molecular beacon performance is required. In this study, molecular beacon performance was evaluated as a function of gold nanoparticle size and its immobilization characteristics. Gold nanoparticles of 4 nm, 15 nm and 87 nm diameter, were immobilized onto glass slides. Each size regime offered distinctive optical properties for fluorescence quenching of molecular dyes that were conjugated to oligonucleotides that were immobilized to the gold nanoparticles. Rigid double stranded DNA was used as a model to place fluorophores at different distances from the gold nanoparticles. The effect of particle size and also the immobilization density of nanoparticles was evaluated. The 4 nm and 87 nm gold nanoparticles offered the highest sensitivity in terms of the change in fluorescence intensity as a function of distance (3-fold improvement for Cy5). The optical properties of the molecular fluorophore was of significance, with Cy5 offering higher contrast ratios than Cy3 due to the red shifted emission spectrum relative to the plasmon peak. A high density of gold nanoparticles reduced contrast ratios, indicating preference for a monolayer of immobilized nanoparticles when considering analytical performance. Molecular beacon probes were then used in place of the double stranded oligonucleotides. There was a strong dependence of molecular beacon performance on the length of a linker used for attachment to the nanoparticle surface. The optimal optical performance was obtained with 4 nm gold nanoparticles that were immobilized as monolayers of low density (5.7*10(11)particles cm(-2)) on glass surfaces. These nanoparticle surfaces offered a 2-fold improvement in analytical performance of the molecular beacons when compared to other nanoparticle sizes investigated. The principles developed in this study would assist in the design of solid phase molecular beacons using gold nanoparticles. PMID- 24216205 TI - Reprint of: Use of a mobile phone for potentiostatic control with low cost paper based microfluidic sensors. AB - By exploiting its ability to play sounds, a mobile phone with suitable software installed can serve the basic functions of a potentiostat in controlling an applied potential to oxidise ECL-active molecules, while the resultant photonic signal is monitored using the camera in video mode. In combination with paper microfluidic sensors this opens significant new possibilities for low-cost, instrument-free sensing. PMID- 24216206 TI - Self-assembly of core-satellite gold nanoparticles for colorimetric detection of copper ions. AB - Molecule-coated nanoparticles are hybrid materials which can be engineered with novel properties. The molecular coating of metal nanoparticles can provide chemical functionality, enabling assembly of the nanoparticles that are important for applications, such as biosensing devices. Herein, we report a new self assembly of core-satellite gold nanoparticles linked by a simple amino acid l Cysteine for biosensing of Cu(2+). The plasmonic properties of core-satellite nano-assemblies were investigated, a new red shifted absorbance peak from about 600 to 800 nm was found, with specific wavelength depending on ratios with assembly of large and small gold nanoparticles. The spectral features obtained using surface-enhanced Raman spectroscopy (SERS) provided strong evidence for the assembly of the Cu(2+) ions to the L-Cysteine molecules leading to the successful formation of the core-satellite Cu(l-Cysteine) complex on the gold surfaces. In addition, a linear relationship between the concentration of mediating Cu(2+) and absorbance of self-assembled gold nanoparticles (GNPs) at 680 nm was obtained. These results strongly address the potential strategy for applying the functionalized GNPs as novel biosensing tools in trace detections of certain metal ions. PMID- 24216207 TI - Analytical isotachophoresis of lactate in human serum using dry film photoresist microfluidic chips compatible with a commercially available field-deployable instrument platform. AB - A dry film resist (DFR) chip compatible with the Agilent Bioanalyzer 2100 was designed and fabricated for use in the analysis of lactate in serum by chip isotachophoresis (ITP). The Agilent Bioanalyzer 2100 is a commercially available field deployable analytical instrument originally developed for the electrophoretic analysis of DNA, RNA and proteins. The DFR chip was designed for the ITP separation of lactate in human serum within 1 min and was made compatible with the Bioanalyzer after packaging in the plastic caddies normally used for the DNA chips. A 20-fold improvement in sensitivity was obtained for the DFR chips in comparison with the standard chips used in earlier work. The limit of detection and limit of quantification for lactate were 24 MUM and 80 MUM, respectively. This new approach enables the use of commercial platforms like the Agilent Bioanalyzer for new applications including the analysis of small molecules. PMID- 24216208 TI - Ion-exchange and hydrophobic interactions affecting selectivity for neutral and charged solutes on three structurally similar agglomerated ion-exchange and mixed mode stationary phases. AB - The nature and extent of mixed-mode retention mechanisms evident for three structurally related, agglomerated, particle-based stationary phases were evaluated. These three agglomerated phases were Thermo Fisher ScientificIon PacAS11-HC - strong anion exchange, Thermo Fisher Scientific IonPac CS10--strong cation-exchange PS-DVB, and the Thermo Fisher Scientific Acclaim Trinity P1silica based substrate, which is commercially marketed as a mixed-mode stationary phase. All studied phases can exhibit zwitterionic and hydrophobic properties, which contribute to the retention of charged organic analytes. A systematic approach was devised to investigate the relative ion-exchange capacities and hydrophobicities for each of the three phases, together with the effect of eluent pH upon selectivity, using a specifically selected range of anionic, cationic and neutral aromatic compounds. Investigation of the strong anion-exchange column and the Trinity P1 mixed-mode substrate, in relation to ion-exchange capacity and pH effects, demonstrated similar retention behaviour for both the anionic and ampholytic solutes, as expected from the structurally related phases. Further evaluation revealed that the ion-exchange selectivity of the mixed-mode phase exhibited properties similar to that of the strong anion-exchange column, with secondary cation-exchange selectivity, albeit with medium to high anion-exchange and cation-exchange capacities, allowing selective retention for each of the anionic, cationic and ampholytic solutes. Observed mixed-mode retention upon the examined phases was found to be a sum of anion- and cation-exchange interactions, secondary ion-exchange and hydrophobic interactions, with possible additional hydrogen bonding. Hydrophobic evaluation of the three phases revealed logP values of 0.38-0.48, suggesting low to medium hydrophobicity. These stationary phases were also benchmarked against traditional reversed-phase substrates namely, octadecylsilica YMC-Pac Pro C18 and neutral MUPS-DVB resin IonPac NS1-5u, yielding logP values of 0.57 and 0.52, respectively. PMID- 24216209 TI - Parallel segmented outlet flow high performance liquid chromatography with multiplexed detection. AB - We describe a new approach to multiplex detection for HPLC, exploiting parallel segmented outlet flow - a new column technology that provides pressure-regulated control of eluate flow through multiple outlet channels, which minimises the additional dead volume associated with conventional post-column flow splitting. Using three detectors: one UV-absorbance and two chemiluminescence systems (tris(2,2'-bipyridine)ruthenium(III) and permanganate), we examine the relative responses for six opium poppy (Papaver somniferum) alkaloids under conventional and multiplexed conditions, where approximately 30% of the eluate was distributed to each detector and the remaining solution directed to a collection vessel. The parallel segmented outlet flow mode of operation offers advantages in terms of solvent consumption, waste generation, total analysis time and solute band volume when applying multiple detectors to HPLC, but the manner in which each detection system is influenced by changes in solute concentration and solution flow rates must be carefully considered. PMID- 24216210 TI - Multiplexed dual second-dimension column comprehensive two-dimensional gas chromatography (GC * 2GC) using thermal modulation and contra-directional second dimension columns. AB - A multiplexed dual-secondary column comprehensive two-dimensional gas chromatography approach (GC*2GC) designed for complex sample analysis is introduced. The approach splits the first-dimension column effluent into two second-dimension columns with different stationary phases, and recombines the two streams into one detector post-separation. The approach produces two single two dimensional chromatograms for each injection. Careful manipulation of thermal modulator timing parameters combined with a novel contra-directional modulation regime facilitates this approach. A selection of 34 laboratory reference compounds containing n-alkanes, alcohols, aromatic hydrocarbons, ketones, esters and halogenated hydrocarbons were analysed to demonstrate the approach. The dual two-dimensional chromatogram from this single detector system provides complementary information due to the unique selectivity of the three separation columns. The results of this proof-of-principle investigation provide significant impetus for further development of GC*2GC-MS methodology. PMID- 24216211 TI - Characterisation of capillary ionic liquid columns for gas chromatography-mass spectrometry analysis of fatty acid methyl esters. AB - Due to their distinct chemical properties, the application of ionic liquid (IL) compounds as gas chromatography (GC) stationary phases offer unique GC separation especially in the analysis of geometric and positional fatty acid methyl ester (FAME) isomers. Elution behaviour of FAME on several commercialised IL capillary columns including phosphonium based SLB-IL59, SLB-IL60, SLB-IL61 and SLB-IL76 and imidazolium based SLB-IL82, SLB-IL100, and SLB-IL111 as well as a general purpose column SLB-5ms, were evaluated in gas chromatography-mass spectrometry (GC-MS) analysis. The phases were further characterised by using a linear solvation energy relationship (LSER) approach according to the equivalent chain length (ECL) index of FAME. Among all tested IL columns, elution temperatures of saturated FAME increased as their McReynolds' polarity value decreased, except for IL60. ECL values increased markedly as the stationary phase polarity increased, particularly for the polyunsaturated FAME. The LSER study indicated a lowest l/e value at 0.864 for IL111, displaying phase selectivity towards unsaturated FAME, with higher peak capacity within a carbon number isomer group. s and e descriptors calculated from LSER were validated by excellent correlation with dipole moments and lowest unoccupied molecular orbital (LUMO) energies, with R(2) values of 0.99 and 0.92 respectively, calculated using GAUSSIAN. PMID- 24216212 TI - Evaluation of comprehensive two-dimensional gas chromatography with flame photometric detection: potential application for sulfur speciation in shale oil. AB - Flame photometric detection in the sulfur channel has been evaluated for sulfur speciation and quantification in comprehensive two-dimensional gas chromatography [GC * GC-FPD(S)] for S-compound speciation in shale extracts. Signal non linearity and potential quenching effects were reportedly major limitations of this detector for analysis of sulfur in complex matrices. However, reliable linear relationships with correlation coefficient >0.99 can be obtained if the sum of the square root of each modulation slice in GC * GC is plotted vs. sulfur concentration. Furthermore, the quenching effects are reduced due to essentially complete separation of S-containing components from the hydrocarbon matrix. An increase of S/N of up to 150 times has been recorded for benzothiophene and dibenzothiophene in GC * GC-FPD when compared to GC-FPD due to the modulation process. As a consequence, 10 times lower detection limits were observed in the former mode. The applicability of the method was demonstrated using shale oil sample extracts. Three sulfur classes were completely separated and the target class (thiophenes) was successfully quantified after the rest of the sample was diverted to the second detector by using a heart-cut strategy. Based on the proposed method, 70% of the sulfur in the shale oil was assigned to the thiophenes, 24% to benzothiophenes, and 5% to dibenzothiophene compounds. PMID- 24216213 TI - Quantitation of hindered amine light stabilizers in plastic materials by high performance liquid chromatography and mass spectrometric detection using electrospray ionization and atmospheric pressure photoionization. AB - In this work new high performance liquid chromatographic methods in combination with mass spectrometry have been developed for the quantitation of hindered amine light stabilizers (HALS) which are commonly used as monomeric and oligomeric species for stabilization of plastic materials. These analytes are difficult to separate under traditional reversed phase conditions. In the present study new silica-based pH stable reversed phases that had become available recently were investigated for HALS analysis, and turned out to be well suited employing mobile phases at a pH of around 11 adjusted by addition of ammonia. Detection was done by mass spectrometry employing both time-of-flight and triple quadrupole mass analyzers. The performance of electrospray ionization (ESI) as well as atmospheric pressure photoionization (APPI) was investigated and compared. Despite the high pH of the mobile phase, an excellent ionization could be obtained in the positive ion mode. ESI provided slightly lower limits of quantitation (on average a factor of 2) in comparison with APPI. The method allowed the quantitation of a range of different HALS down to 0.05-0.005% (depending on the HALS) in polymeric materials. Sample preparation consisted in dissolving the sample in toluene and precipitation of the polymer with acetone. The procedure can be routinely applied to aging tests of plastic materials in order to predict the lifetime of plastic components. PMID- 24216214 TI - Comprehensive sample analysis using high performance liquid chromatography with multi-detection. AB - Herein we assess the separation space offered by a liquid chromatography system with an optimised uni-dimensional separation for the determination of the key chemical entities in the highly complex matrix of a tobacco leaf extract. Multiple modes of detection, including UV-visible absorbance, chemiluminescence (acidic potassium permanganate, manganese(IV), and tris(2,2' bipyridine)ruthenium(III)), mass spectrometry and DPPH radical scavenging were used in an attempt to systematically reduce the data complexity of the sample whilst obtaining a greater degree of molecule-specific information. A large amount of chemical data was obtained, but several limitations in the ability to assign detector responses to particular compounds, even with the aid of complementary detection systems, were observed. Thirty-three compounds were detected via MS on the tobacco extract and 12 out of 32 compounds gave a peak height ratio (PHR) greater than 0.33 on one or more detectors. This paper serves as a case study of these limitations, illustrating why multidimensional chromatography is an important consideration when developing a comprehensive chemical detection system. PMID- 24216215 TI - Towards identification of traditional European and indigenous Australian paint binders using pyrolysis gas chromatography mass spectrometry. AB - We report a pyrolysis GC-MS method capable of analysing Indigenous Australian and European binders typically used in the manufacture of culturally important painted works. Eleven different traditional European binders and ten different Indigenous Australian binders were examined. The method allows discrimination between highly complex and impure lipid, resin, polysaccharide, wax, and protein based binders. Each was found to have characteristic pyrolysis products that were unique to the binder material, demonstrating the potential for differentiation of these binders on Australian Aboriginal artworks towards identification and conservation of cultural heritage. PMID- 24216216 TI - Staphylococcus aureus enterotoxin B-induced endoplasmic reticulum stress response is associated with chronic rhinosinusitis with nasal polyposis. AB - OBJECTIVE: Staphylococcus aureus enterotoxin B (SEB) might participate in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the exact mechanism of polyp formation in CRSwNP remains unclear. Since the endoplasmic reticulum (ER) stress response is closely associated with chronic inflammation, we investigated the association between ER stress and SEB in the pathogenesis of CRSwNP. DESIGN AND METHODS: Twenty-three CRSwNP patients with eosinophilic polyps (EP) or non-eosinophilic polyps (NEP) and 10 healthy subjects who were undergoing septoplasty were enrolled in this study. ER stress response was investigated using immunohistochemical staining and Western blotting. RESULTS: We show in this study that there are significantly more SEB-positive cells and higher production of reactive oxygen species (ROS) in the epithelial layer of EP than NEP or control tissue. Both SEB and protein A were detected strongly in tissues from patients with CRSwNP. We observed SEB induced the ER stress response in RPMI 2650 cells. GRP78 elevation by SEB was reduced by ROS scavenger pretreatment. In addition, the induction of GRP78 and p47 phox was increased significantly in EP compared with NEP or control mucosa. CONCLUSIONS: SEB may induce ER stress via ROS production in CRSwNP. Therefore, we suggest that SEB-induced ER stress may play important roles in the pathogenesis of nasal polyposis. PMID- 24216217 TI - Treating Alzheimer's disease with monoclonal antibodies: current status and outlook for the future. AB - In the past decade, Alzheimer's disease drug discovery has been directed at 'disease modifying drugs' that are able to counteract the progression of Alzheimer's disease by intervening in specific parts of its neuropathological process. Passive immunization with monoclonal antibodies (mAbs) may be able to clear toxic amyloid-beta species either directly or through microglia or complement activation, thereby halting the amyloid cascade and preventing neurodegeneration and cognitive and functional decline. Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results. Possible explanations could be that these compounds were either targeting the wrong amyloid-beta species, or were given too late in the disease process. Several new mAbs targeting various amyloid-beta epitopes are now being tested in ongoing phase 2 and 3 clinical trials. The present review discusses the various mAbs aimed at amyloid-beta, summarizes trial results and provides an outlook for the future. PMID- 24216220 TI - The role of red cell distribution width in the diagnosis of acute appendicitis: a retrospective case-controlled study. AB - PURPOSE: The aim of this study was to seek whether red cell distribution width (RDW) has a role in the diagnosis of acute appendicitis. It was also aimed to show the relationship of RDW with leukocyte count and C-reactive protein (CRP) level. METHODS: This study was conducted via retrospective assessment of the hospital records of the adult patients who were operated for acute appendicitis between January 2010 and February 2013 and had a pathology report that confirmed the diagnosis of acute appendicitis. The patients in the control group were selected from healthy adults of similar age who applied to check-up clinic. Age, gender, leukocyte count, CRP, and RDW values were recorded. This study is a case controlled retrospective clinical study. RESULTS: A total of 590 patients in the acute appendicitis group and 121 patients in the control group were included, making up a total of 711 subjects. The mean RDW levels were 15.4 +/- 1.5% in the acute appendicitis group, while 15.9 +/- 1.4% in the control group. CRP, leukocyte count were significantly higher in the acute appendicitis group, and RDW level were significantly lower in the acute appendicitis group (p < 0.001, p < 0.001, p = 0.001, respectively). RDW, leukocyte count, and CRP had a sensitivity and specificity of 47% and 67%; 91% and 74%; and 97% and 41%, respectively in acute appendicitis. RDW was not correlated with CRP and leukocyte levels. However, we found a correlation between CRP and leukocyte levels. CONCLUSION: RDW level was lower in patients with acute appendicitis. The magnitude of difference in RDW seen between acute appendicitis and controls was so slight as to be of no utility in diagnostic testing. PMID- 24216219 TI - A randomized trial of the clinical utility of genetic testing for obesity: design and implementation considerations. AB - BACKGROUND: Obesity rates in the United States have escalated in recent decades and present a major challenge in public health prevention efforts. Currently, testing to identify genetic risk for obesity is readily available through several direct-to-consumer companies. Despite the availability of this type of testing, there is a paucity of evidence as to whether providing people with personal genetic information on obesity risk will facilitate or impede desired behavioral responses. PURPOSE: We describe the key issues in the design and implementation of a randomized controlled trial examining the clinical utility of providing genetic risk information for obesity. METHODS: Participants are being recruited from the Coriell Personalized Medicine Collaborative, an ongoing, longitudinal research cohort study designed to determine the utility of personal genome information in health management and clinical decision making. The primary focus of the ancillary Obesity Risk Communication Study is to determine whether genetic risk information added value to traditional communication efforts for obesity, which are based on lifestyle risk factors. The trial employs a 2 * 2 factorial design in order to examine the effects of providing genetic risk information for obesity, alone or in combination with lifestyle risk information, on participants' psychological responses, behavioral intentions, health behaviors, and weight. RESULTS: The factorial design generated four experimental arms based on communication of estimated risk to participants: (1) no risk feedback (control), (2) genetic risk only, (3) lifestyle risk only, and (4) both genetic and lifestyle risk (combined). Key issues in study design pertained to the selection of algorithms to estimate lifestyle risk and determination of information to be provided to participants assigned to each experimental arm to achieve a balance between clinical standards and methodological rigor. Following the launch of the trial in September 2011, implementation challenges pertaining to low enrollment and differential attrition became apparent and required immediate attention and modifications to the study protocol. Although monitoring of these efforts is ongoing, initial observations show a doubling of enrollment and reduced attrition. LIMITATIONS: The trial is evaluating the short-term impact of providing obesity risk information as participants are followed for only 3 months. This study is built upon the structure of an existing personalized medicine study wherein participants have been provided with genetic information for other diseases. This nesting in a larger study may attenuate the effects of obesity risk information and has implications for the generalizability of study findings. CONCLUSIONS: This randomized trial examines value of obesity genetic information, both when provided independently and when combined with lifestyle risk assessment, to motivate individuals to engage in healthy lifestyle behaviors. Study findings will guide future intervention efforts to effectively communicate genetic risk information. PMID- 24216221 TI - Months of asynchrony in offspring production but synchronous adult emergence: the role of diapause in an ectoparasite's life cycle. AB - Off-host stages of temperate zone ectoparasites must overcome two challenges: coping with unfavorable seasons and synchronizing their life cycles with host availability. In general, little is known about the seasonal cycles of insect ectoparasites of warm-blooded animals. The current study investigates the unusual phenology of a viviparous hippoboscid fly, the deer ked (Lipoptena cervi L.), that parasitizes boreal cervids. Despite months of asynchrony in offspring production, the adults emerge synchronously in mid-August across the northern boreal zone. We examined the role of diapause variation in the synchronization of life cycles by testing adult emergence success and time in relation to offspring birth month (October to April) and with respect to chilling time and photoperiod. Unexpectedly, we found that photoperiod had no role in regulating the life cycle, but diapause was maintained as long as pupae were exposed to cold. Pupae born before February needed a slightly longer exposure to high temperatures to terminate diapause if the cold period was short. Despite the apparent importance of a long period of chilling for life cycle synchrony, it was not required to terminate diapause. This finding of cold mainly preventing, rather than promoting, diapause termination is not novel among temperate insects, but it is rare. Slow diapause termination as a response to exceptionally long exposure to high, not low, temperatures seems to be a cornerstone for synchronizing the life cycle in the deer ked. PMID- 24216222 TI - Threats and opportunities of plant pathogenic bacteria. AB - Plant pathogenic bacteria can have devastating effects on plant productivity and yield. Nevertheless, because these often soil-dwelling bacteria have evolved to interact with eukaryotes, they generally exhibit a strong adaptivity, a versatile metabolism, and ingenious mechanisms tailored to modify the development of their hosts. Consequently, besides being a threat for agricultural practices, phytopathogens may also represent opportunities for plant production or be useful for specific biotechnological applications. Here, we illustrate this idea by reviewing the pathogenic strategies and the (potential) uses of five very different (hemi)biotrophic plant pathogenic bacteria: Agrobacterium tumefaciens, A. rhizogenes, Rhodococcus fascians, scab-inducing Streptomyces spp., and Pseudomonas syringae. PMID- 24216218 TI - Recruitment and retention of participants for an international type 1 diabetes prevention trial: a coordinators' perspective. AB - BACKGROUND: The Trial to Reduce Insulin Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR) is the first multicenter international type 1 diabetes (T1D) prevention trial to be undertaken. A unique feature of TRIGR has been recruitment of eligible pregnant women and enrollment of newborns for long term follow-up assessments. PURPOSE: Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators. METHODS: TRIGR was designed to test whether weaning to formula containing hydrolyzed versus intact cow's milk protein would be efficacious in decreasing risk for development of T1D-associated autoantibodies and T1D among infants identified to be at increased risk for T1D based on their human leukocyte antigen (HLA) profile and family history. Multiple strategies tailored to local issues were required to enroll and follow the target number of infants. RESULTS: This study was conducted in the United States, Canada, Australia, and 12 countries in Europe. Of the 5606 mothers registered worldwide, 5000 of their infants were randomized. Of these, 2159 were HLA eligible and enrolled in the 8 month intervention and 10-year follow-up phases of this study. The TRIGR study met the accrual goal after 4.7 years of recruitment, 2.7 years longer than projected initially. Challenges included difficulty in finding fathers with T1D, a higher than expected rate of premature delivery among T1D mothers, and implementation of new privacy regulations mid-trial. The majority of participants were recruited from primary care antenatal clinics located near the study centers and from a general hospital or pediatric center that was affiliated with a TRIGR Study center. Internet and magazine advertisements were found to be useful for recruitment of families. Alternative follow-up strategies are offered to families who wish to reduce or discontinue participation. LIMITATIONS: Our experience is limited to a single international multicenter trial. CONCLUSIONS: TRIGR coordinators played key roles in the recruitment and intervention periods and continue to be instrumental in retaining families and children during the 10-year follow-up period for each child. PMID- 24216224 TI - The heterothallic sugarbeet pathogen Cercospora beticola contains exon fragments of both MAT genes that are homogenized by concerted evolution. AB - Dothideomycetes is one of the most ecologically diverse and economically important classes of fungi. Sexual reproduction in this group is governed by mating type (MAT) genes at the MAT1 locus. Self-sterile (heterothallic) species contain one of two genes at MAT1 (MAT1-1-1 or MAT1-2-1) and only isolates of opposite mating type are sexually compatible. In contrast, self-fertile (homothallic) species contain both MAT genes at MAT1. Knowledge of the reproductive capacities of plant pathogens are of particular interest because recombining populations tend to be more difficult to manage in agricultural settings. In this study, we sequenced MAT1 in the heterothallic Dothideomycete fungus Cercospora beticola to gain insight into the reproductive capabilities of this important plant pathogen. In addition to the expected MAT gene at MAT1, each isolate contained fragments of both MAT1-1-1 and MAT1-2-1 at ostensibly random loci across the genome. When MAT fragments from each locus were manually assembled, they reconstituted MAT1-1-1 and MAT1-2-1 exons with high identity, suggesting a retroposition event occurred in a homothallic ancestor in which both MAT genes were fused. The genome sequences of related taxa revealed that MAT gene fragment pattern of Cercospora zeae-maydis was analogous to C. beticola. In contrast, the genome of more distantly related Mycosphaerella graminicola did not contain MAT fragments. Although fragments occurred in syntenic regions of the C. beticola and C. zeae-maydis genomes, each MAT fragment was more closely related to the intact MAT gene of the same species. Taken together, these data suggest MAT genes fragmented after divergence of M. graminicola from the remaining taxa, and concerted evolution functioned to homogenize MAT fragments and MAT genes in each species. PMID- 24216223 TI - Functional connectivity and graph theory in preclinical Alzheimer's disease. AB - Alzheimer's disease (AD) has a long preclinical phase in which amyloid and tau cerebral pathology accumulate without producing cognitive symptoms. Resting state functional connectivity magnetic resonance imaging has demonstrated that brain networks degrade during symptomatic AD. It is unclear to what extent these degradations exist before symptomatic onset. In this study, we investigated graph theory metrics of functional integration (path length), functional segregation (clustering coefficient), and functional distinctness (modularity) as a function of disease severity. Further, we assessed whether these graph metrics were affected in cognitively normal participants with cerebrospinal fluid evidence of preclinical AD. Clustering coefficient and modularity, but not path length, were reduced in AD. Cognitively normal participants who harbored AD biomarker pathology also showed reduced values in these graph measures, demonstrating brain changes similar to, but smaller than, symptomatic AD. Only modularity was significantly affected by age. We also demonstrate that AD has a particular effect on hub-like regions in the brain. We conclude that AD causes large-scale disconnection that is present before onset of symptoms. PMID- 24216225 TI - Current challenges and clinical investigations of epidermal growth factor receptor (EGFR)- and ErbB family-targeted agents in the treatment of head and neck squamous cell carcinoma (HNSCC). AB - Overexpression of the epidermal growth factor receptor (EGFR) is a common characteristic of head and neck squamous cell carcinomas (HNSCC). Cetuximab is a chimeric anti-EGFR monoclonal antibody (mAb) with multiple approved indications in HNSCC, including with radiation therapy (RT) for locoregionally advanced disease, as monotherapy after platinum progression, and with platinum/5 fluorouracil for recurrent or metastatic disease. There remain, however, numerous unanswered questions regarding the optimal use of cetuximab in HNSCC, including patient selection, its mechanisms of action and resistance, the effect of human papillomavirus status on outcomes, its role when combined with induction chemotherapy or adjuvant radiation, and optimal management of skin toxicity and hypersensitivity reactions. In addition, a variety of other anti-EGFR agents (the multitargeted small molecule tyrosine kinase inhibitors [TKIs] lapatinib, dacomitinib, and afatinib and the anti-EGFR mAbs zalutumumab, nimotuzumab, and panitumumab) are currently under investigation in phase II and III clinical trials in different HNSCC therapeutic settings. The anti-EGFR TKI erlotinib is currently in phase III development for oral cancer prevention. Numerous other drugs are in earlier stages of development for HNSCC treatment, including novel anti-EGFR mAbs (MEHD7945A, necitumumab, and RO5083945), small-molecule TKIs (vandetanib, icotinib, and CUDC-101), EGFR antisense, various add-on therapies to radiation and chemotherapy (bevacizumab, interleukin-12, lenalidomide, alisertib, and VTX-2337), and drugs (temsirolimus, everolimus, OSI-906, dasatinib, and PX 866) intended to overcome resistance to anti-EGFR agents. Overall, a wealth of clinical trial data is expected in the coming years, with the potential to modify significantly the approach to anti-EGFR therapy for HNSCC. PMID- 24216226 TI - Liposomal nanomedicines in the treatment of prostate cancer. AB - Prostate cancer is the most common cancer type and the second leading cause of death from cancer in males. In most cases, no curative treatment options are available for metastatic castration-resistant prostate cancer as these tumors are highly resistant to chemotherapy. Targeted drug delivery, using liposomal drug delivery systems, is an attractive approach to enhance the efficacy of anticancer drugs and prevent side effects, thereby potentially increasing the therapeutic index. In most preclinical prostate cancer studies, passive liposomal targeting of anticancer drugs (caused by enhanced permeability and retention of the therapeutic compound) leads to an increased antitumor efficacy and decreased side effects compared to non-targeted drugs. As a result, the total effective dose of anticancer drugs can be substantially decreased. Active (ligand-mediated) liposomal targeting of tumor cells and/or tumor-associated stromal cells display beneficial effects, but only limited preclinical studies were reported. To date, clinical studies in prostate carcinoma have been performed with liposomal doxorubicin only. These studies showed that long-circulating, PEGylated, liposomal doxorubicin generally outperforms conventional short-circulating liposomal doxorubicin, stressing the importance of passive tumor targeting for this drug in prostate carcinoma. In this review, we provide an overview of the (pre)clinical studies that focus on liposomal drug delivery in prostate carcinoma. PMID- 24216227 TI - Reply: To PMID 23790348. PMID- 24216228 TI - A mathematical model to predict the effect of heat recovery on the wastewater temperature in sewers. AB - Raw wastewater contains considerable amounts of energy that can be recovered by means of a heat pump and a heat exchanger installed in the sewer. The technique is well established, and there are approximately 50 facilities in Switzerland, many of which have been successfully using this technique for years. The planning of new facilities requires predictions of the effect of heat recovery on the wastewater temperature in the sewer because altered wastewater temperatures may cause problems for the biological processes used in wastewater treatment plants and receiving waters. A mathematical model is presented that calculates the discharge in a sewer conduit and the spatial profiles and dynamics of the temperature in the wastewater, sewer headspace, pipe, and surrounding soil. The model was implemented in the simulation program TEMPEST and was used to evaluate measured time series of discharge and temperatures. It was found that the model adequately reproduces the measured data and that the temperature and thermal conductivity of the soil and the distance between the sewer pipe and undisturbed soil are the most sensitive model parameters. The temporary storage of heat in the pipe wall and the exchange of heat between wastewater and the pipe wall are the most important processes for heat transfer. The model can be used as a tool to determine the optimal site for heat recovery and the maximal amount of extractable heat. PMID- 24216229 TI - Drivers of microbial community composition in mesophilic and thermophilic temperature-phased anaerobic digestion pre-treatment reactors. AB - Temperature-phased anaerobic digestion (TPAD) is an emerging technology that facilitates improved performance and pathogen destruction in anaerobic sewage sludge digestion by optimising conditions for 1) hydrolytic and acidogenic organisms in a first-stage/pre-treatment reactor and then 2) methogenic populations in a second stage reactor. Pre-treatment reactors are typically operated at 55-65 degrees C and as such select for thermophilic bacterial communities. However, details of key microbial populations in hydrolytic communities and links to functionality are very limited. In this study, experimental thermophilic pre-treatment (TP) and control mesophilic pre-treatment (MP) reactors were operated as first-stages of TPAD systems treating activated sludge for 340 days. The TP system was operated sequentially at 50, 60 and 65 degrees C, while the MP rector was held at 35 degrees C for the entire period. The composition of microbial communities associated with the MP and TP pre treatment reactors was characterised weekly using terminal-restriction fragment length polymorphism (T-RFLP) supported by clone library sequencing of 16S rRNA gene amplicons. The outcomes of this approach were confirmed using 454 pyrosequencing of gene amplicons and fluorescence in-situ hybridisation (FISH). TP associated bacterial communities were dominated by populations affiliated to the Firmicutes, Thermotogae, Proteobacteria and Chloroflexi. In particular there was a progression from Thermotogae to Lutispora and Coprothermobacter and diversity decreased as temperature and hydrolysis performance increased. While change in the composition of TP associated bacterial communities was attributable to temperature, that of MP associated bacterial communities was related to the composition of the incoming feed. This study determined processes driving the dynamics of key microbial populations that are correlated with an enhanced hydrolytic functionality of the TPAD system. PMID- 24216230 TI - Permeability and selectivity of reverse osmosis membranes: correlation to swelling revisited. AB - Membrane swelling governs both rejection of solutes and permeability of polymeric membranes, however very few data have been available on swelling in water of salt rejecting reverse osmosis (RO) membranes. This study assesses swelling, thickness and their relation to water permeability for four commercial polyamide (PA) RO membranes (SWC4+, ESPA1, XLE and BW30) using atomic force microscopy (AFM) and attenuated total reflection Fourier transform IR spectroscopy (ATR-FTIR). ATR FTIR offered a significantly improved estimate of the actual barrier thickness of PA, given AFM is biased by porosity ("fluffy parts") or wiggling of the active layer or presence of a coating layer. Thus obtained intrinsic permeability (permeability times thickness) and selectivity of aromatic polyamides plotted versus swelling falls well on a general trend, along with previously reported data on several common materials showing RO and NF selectivity. The observed general trend may be rationalized by viewing the polymers as a random composite medium containing molecularly small pores. The results suggest that the combination of a rigid low dielectric matrix, limiting the pore size, with multiple hydrophilic H-bonding sites may be a common feature of RO/NF membranes, allowing both high permeability and selectivity. PMID- 24216232 TI - Behaviour and fate of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in drinking water treatment: a review. AB - This article reviews perfluoroalkyl and polyfluoroalkyl substance (PFAS) characteristics, their occurrence in surface water, and their fate in drinking water treatment processes. PFASs have been detected globally in the aquatic environment including drinking water at trace concentrations and due, in part, to their persistence in human tissue some are being investigated for regulation. They are aliphatic compounds containing saturated carbon-fluorine bonds and are resistant to chemical, physical, and biological degradation. Functional groups, carbon chain length, and hydrophilicity/hydrophobicity are some of the important structural properties of PFASs that affect their fate during drinking water treatment. Full-scale drinking water treatment plant occurrence data indicate that PFASs, if present in raw water, are not substantially removed by most drinking water treatment processes including coagulation, flocculation, sedimentation, filtration, biofiltration, oxidation (chlorination, ozonation, AOPs), UV irradiation, and low pressure membranes. Early observations suggest that activated carbon adsorption, ion exchange, and high pressure membrane filtration may be effective in controlling these contaminants. However, branched isomers and the increasingly used shorter chain PFAS replacement products may be problematic as it pertains to the accurate assessment of PFAS behaviour through drinking water treatment processes since only limited information is available for these PFASs. PMID- 24216231 TI - Extremely elevated methyl mercury levels in water, sediment and organisms in a Romanian reservoir affected by release of mercury from a chlor-alkali plant. AB - We examined mercury (Hg) biogeochemistry and biomagnification in the Babeni Reservoir, a system strongly affected by the release of Hg from a chlor-alkali plant. Total mercury (THg) concentrations in river water reached 88 ng L(-1) but decreased rapidly in the reservoir (to 9 ng L(-1)). In contrast, monomethylmercury (MMHg) concentrations increased from the upstream part of the reservoir to the central part (0.7 ng L(-1)), suggesting high methylation within the reservoir. Moreover, vertical water column profiles of THg and MMHg indicated that Hg methylation mainly occurred deep in the water column and at the sediment water interface. The discharge of Hg from a chlor-alkali plant in Valcea region caused the highest MMHg concentrations ever found in non-piscivorous fish worldwide. MMHg concentrations and bioconcentration factors (BCF) of plankton and macrophytes revealed that the highest biomagnification of MMHg takes place in primary producers. PMID- 24216233 TI - Editorial: Microbial ecology. PMID- 24216234 TI - Optimization of interferon gamma ELISPOT assay to detect human cytomegalovirus specific T-cell responses in solid organ transplants. AB - Assessing the CMV specific CMI in transplant subjects represents a promising strategy to determine the risk of infection on individual basis. In this study 61 adult CMV IgG seropositive solid organ transplant recipients were examined in order to improve the efficacy of CMI detection. For this purpose, pair-wise comparisons were conducted comparing positive control stimuli PWM and PMA/iono and CMV stimuli, pp65 peptide pool and whole CMV particle. Rosette pre-depletion of blood was also investigated for detecting CD4+ or CD8+ T-cell responses using the IFN-g ELISPOT assay. In the time-points 30-180 days after transplantation, PMA/iono produced statistically significant higher responses compared to PWM, probably because PMA/iono activation pathway is independent from the effect of immunosuppressive drugs. The data showed that 11% of transplant patients displayed very low or undetectable responses to pp65 peptide pool antigen while having sustained high responses to whole CMV particle. In addition, in all the subjects analyzed, CMI responses to CMV particle produced a statistically significant higher number of spots compared to pp65 peptide pool antigen. Rosette pre-depletion of whole blood proved to be effective in detecting CD4+ or CD8+ T cell responses similarly to flow cytometry. Taken together, the following recommendations are suggested to optimize the CMV-ELISPOT for transplantation settings: (1) use PMA/iono as positive control; (2) whole virus particle should be used to avoid peptide-related false negative responses; (3) a rosette pre depletion step may be useful to detect CD4+ or CD8+ T-cell responses. PMID- 24216235 TI - High-yield soluble expression of recombinant influenza virus antigens from Escherichia coli and their potential uses in diagnosis. AB - Although antiviral drugs and vaccines have been successful for mitigating influenza virus infections, the lack of general technical platform for the timely supply of soluble and highly purified influenza viral antigens presents a serious bottleneck for the subsequent analysis for the effective control of the viral disease. Using the Escherichia coli (E. coli) lysyl tRNA synthetase (LysRS) as a novel fusion partner, this study reports the soluble expression of influenza viral proteins in E. coli host, construction of antibody library against the virus, and detection of anti-influenza antibodies using the expressed viral antigens. When influenza A and B viral proteins were fused with the LysRS, the fusion proteins were expressed predominantly as soluble forms and their production yields were high enough to be amenable to immunization protocols in rabbits for antibody generation. The produced antibodies showed high level binding specificity against the respective viral proteins, with cross-reactivity across heterologous viruses within the same type of influenza viruses. In addition, LysRS-HA fusion protein could bind specifically to anti-HA antibodies in the virus-infected mouse serum in widely accepted two detection methods, Western blot and ELISA. These results present a convenient tool for the production of antibodies specific to the virus as well as the rapid detection of influenza viral infections, ultimately contributing to the control of influenza viruses including highly pathogenic H5N1, pandemic H1N1, or the recent H7N9 influenza viruses. PMID- 24216236 TI - Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples. AB - Human papillomavirus (HPV) DNA tests tend to show high sensitivity, but poor specificity in detecting high-grade cervical lesions. This study aimed to explore the clinical performance of QuantiVirus((r)) HPV E6/E7 mRNA in identifying >=Grade 2 cervical intraepithelial neoplasia. Thin-prep((r)) liquid based cytology test (LBC) samples were collected from October 2009 to October 2011 from women who underwent outpatient hospital-based gynecological screening. LBC samples were processed for E6/E7 mRNA detection and HPV DNA detection. Of 335 patients, 135 (40.3%) were HPV E6/E7 mRNA positive for high-risk HPV subtypes. The positivity rate of HPV E6/E7 mRNA increased with the severity of cytological and histological evaluation. An optimal cut-off value of >=567copies/ml was determined using receiver operating characteristic (ROC) curve, and positive predictive value and negative predictive value of cut-off value (>=567copies/ml) were higher than those of E6/E7 mRNA positivity only, but not significant. QuantiVirus((r)) HPV E6/E7 mRNA testing may be a valuable tool in triage for identifying >=Grade 2 cervical intraepithelial neoplasia. A high specificity and a low positivity rate of E6/E7mRNA testing as a triage test in HPV DNA-positive women can be translated into a low referral for colposcopy. Studies composed of large population-based samples of women and with rigorous disease ascertainment, are needed to establish the optimal cut-off point based on ROC curve analysis. PMID- 24216237 TI - The potential of lipopolysaccharide-binding protein to predict the severity and prognosis of cirrhotic patients with severe sepsis. PMID- 24216238 TI - Comments on the EMA draft guideline: final steps towards a harmonized view between regulators and industry. PMID- 24216239 TI - MODRIC - Manipulation of drugs in children. PMID- 24216240 TI - Mixing medicines with foods and drinks - latest regulatory considerations. PMID- 24216241 TI - Evidence based design of face masks for infants. PMID- 24216242 TI - Challenges of pediatric formulations: a FDA science perspective. PMID- 24216243 TI - Buccolam: the first centralized paediatric use marketing authorization. PMID- 24216244 TI - Successful development of an orphan drug for the pediatric population. PMID- 24216245 TI - Microparticulates as drug carriers for pediatric use. PMID- 24216246 TI - Prevention of vitamin D insufficiency in Switzerland: a never-ending story. PMID- 24216247 TI - European Study of Neonatal Exposure to Excipients: an update. PMID- 24216248 TI - Impairment of alpha1-adrenoceptor-mediated calcium influx in contralateral carotids following balloon injury: beneficial effect of superoxide anions. AB - There are many evidences indicating a compensatory mechanism in contralateral carotids following balloon injury. Previously it was observed alpha1-adrenoceptor mediated hyper-reactivity and impairment of calcium influx in contralateral carotids 4 days after injury. At a later stage, alpha1-adrenoceptor-mediated contraction is similar to the control and we hypothesized that downstream signaling was normal. In the present study, we aimed to evaluate alpha1 adrenoceptor-mediated calcium influx in contralateral carotids 15 days after balloon injury. Concentration-response curves for CaCl2 in presence of the alpha1 adrenoceptor agonist (phenylephrine), measurement of the intracellular calcium transient and the levels of reactive oxygen species using fluorescent dyes were performed in control and contralateral carotids. Phenylephrine-induced intracellular calcium mobilization in contralateral carotids was not altered, while phenylephrine-induced calcium influx was reduced in the contralateral artery. Nitric oxide synthase inhibitors, L-NAME or L-NNA, restored this response, but nitrite and nitrate levels were decreased in contralateral carotids. Additionally, a rise in oxygen free radicals was observed in contralateral carotids. Furthermore, Tiron, a superoxide anion scavenger, restored alpha1-adrenoceptor-mediated calcium influx in contralateral carotids to the control level. Similar results were observed with the selective potassium channels blockers 4-aminopyridine and charybdotoxin. In conclusion, data showed that balloon catheter injury resulted in increased superoxide anions levels, activation of potassium channels (Kv and BKCa), inhibition of calcium channels (Cav) and preservation of alpha1-adrenoceptor-mediated contraction at a later stage after injury. PMID- 24216249 TI - Quantitative pharmacological analyses of the interaction between flumazenil and midazolam in monkeys discriminating midazolam: Determination of the functional half life of flumazenil. AB - The duration of action of a drug is commonly estimated using plasma concentration, which is not always practical to obtain or an accurate estimate of functional half life. For example, flumazenil is used clinically to reverse the effects of benzodiazepines like midazolam; however, its elimination can be altered by other drugs, including some benzodiazepines, thereby altering its half life. This study used Schild analyses to characterize antagonism of midazolam by flumazenil and determine the functional half life of flumazenil. Four monkeys discriminated 0.178mg/kg midazolam while responding under a fixed-ratio 10 schedule of stimulus-shock termination; flumazenil was given at various times before determination of a midazolam dose-effect curve. There was a time-related decrease in the magnitude of shift of the midazolam dose-effect curve as the interval between flumazenil and midazolam increased. The potency of flumazenil, estimated by apparent pA2 values (95% CI), was 7.30 (7.12, 7.49), 7.17 (7.03, 7.31), 6.91 (6.72, 7.10) and 6.80 (6.67, 6.92) at 15, 30, 60 and 120min after flumazenil administration, respectively. The functional half life of flumazenil, derived from potency estimates, was 57+/-13min. Thus, increasing the interval between flumazenil and midazolam causes orderly decreases in flumazenil potency; however, across a broad range of conditions, the qualitative nature of the interaction does not change, as indicated by slopes of Schild plots at all time points that are not different from unity. Differences in potency of flumazenil are therefore due to elimination of flumazenil and not due to pharmacodynamic changes over time. PMID- 24216250 TI - DataHigh: graphical user interface for visualizing and interacting with high dimensional neural activity. AB - OBJECTIVE: Analyzing and interpreting the activity of a heterogeneous population of neurons can be challenging, especially as the number of neurons, experimental trials, and experimental conditions increases. One approach is to extract a set of latent variables that succinctly captures the prominent co-fluctuation patterns across the neural population. A key problem is that the number of latent variables needed to adequately describe the population activity is often greater than 3, thereby preventing direct visualization of the latent space. By visualizing a small number of 2-d projections of the latent space or each latent variable individually, it is easy to miss salient features of the population activity. APPROACH: To address this limitation, we developed a Matlab graphical user interface (called DataHigh) that allows the user to quickly and smoothly navigate through a continuum of different 2-d projections of the latent space. We also implemented a suite of additional visualization tools (including playing out population activity timecourses as a movie and displaying summary statistics, such as covariance ellipses and average timecourses) and an optional tool for performing dimensionality reduction. MAIN RESULTS: To demonstrate the utility and versatility of DataHigh, we used it to analyze single-trial spike count and single-trial timecourse population activity recorded using a multi-electrode array, as well as trial-averaged population activity recorded using single electrodes. SIGNIFICANCE: DataHigh was developed to fulfil a need for visualization in exploratory neural data analysis, which can provide intuition that is critical for building scientific hypotheses and models of population activity. PMID- 24216251 TI - Wall paintings studied using Raman spectroscopy: a comparative study between various assays of cross sections and external layers. AB - This work describes a comparative study between in situ applications of portable Raman spectroscopy and direct laboratory measurements using micro-Raman spectroscopy on the surface of small samples and of cross sections. The study was performed using wall paintings from different sites of the Alcazar of Seville. Little information was obtained using a portable Raman spectrometer due to the presence of an acrylic polymer, calcium oxalate, calcite and gypsum that was formed or deposited on the surface. The pigments responsible for different colours, except cinnabar, were not detected by the micro-Raman spectroscopy study of the surface of small samples taken from the wall paintings due to the presence of surface contaminants. The pigments and plaster were characterised using cross sections. The black colour consisted of carbon black. The red layers were formed by cinnabar and white lead or by iron oxides. The green and white colours were composed of green emerald or atacamite and calcite, respectively. Pb3O4 has also been characterised. The white layers (plaster) located under the colour layers consisted of calcite, quartz and feldspars. The fresco technique was used to create the wall paintings. A wall painting located on a gypsum layer was also studied. The Naples yellow in this wall painting was not characterised due to the presence of glue and oils. This study showed the advantage of studying cross sections to completely characterise the pigments and plaster in the studied wall paintings. PMID- 24216252 TI - Spectral properties of highly selective chemosensor for Hg2+. AB - A (E)-2-(2-(2-(1H-indol-3-yl)vinyl)-4H-chromen-4-ylidene)malononitrile (dye 1) was synthesized and its cation sensing properties in DMSO were investigated by UV vis spectroscopy. Upon the addition of Hg2+, the solution of dye 1 showed color change and the absorption band shows a formation of a 1:1 dye 1-Hg2+ coordination complex. The dye 1 exhibited high selectivity for Hg2+ as compared with other cations. Interestingly, the dye 1-F- complex also could be recovered by adding Hg2+. We have investigated the ability of complex formation based on the association constant, Kass; the binding ability for the complex formation of dye 1-F- and Hg2+ is greater than that of the dye 1 with F-. PMID- 24216253 TI - Chromogenic sensing of biological thiols using squarylium dye. AB - A new highly selective probe for biothiols, squarylium dye (SQ), was designed and synthesized. The probe displayed a color change from blue to colorless upon reaction with biothilos such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH). The competition experiments revealed that no obvious interference was observed by performing the titration with the mixtures of Cys and other amino acids. The results indicated that SQ was highly selective for Cys detection. Moreover, SQ could also serve as a "naked-eye" probe for Cys with a minimum detectable concentration of approximately 4 MUM. PMID- 24216254 TI - Delayed drainage versus autotransfusion drainage and routine drainage after total knee arthroplasty: a comparative study. AB - BACKGROUND: The purpose of this research is to compare the clinical results of different drainage methods in total knee arthroplasty (TKA). METHODS: This retrospective comparative study included 55 patients who accepted primary unilateral TKA between October 2010 and November 2012. The patients were classified according to the drainage method used: 25 patients in the autotransfusion drainage group, 12 patients in the delayed drainage group, and 18 patients in the routine drainage group. Otherwise, the same operative procedures and postoperative care were applied to all patients. The variables recorded included total amount of postoperative drainage (including intraoperative blood loss); cases of allogenic blood transfusion; body temperatures on postoperative days 1, 3, and 7; and pre- and postoperative hemoglobin level. Some other elements such as postoperative swelling, range of motion, and wound healing were also compared. RESULTS: Patients who underwent autotransfusion were found to have an amount of drainage (799.2 +/- 196.7 mL) significantly greater than that in the routine drainage group (666.1 +/- 155.0 mL), which in turn was significantly greater than that in the delayed drainage group (381.7 +/- 129.2 mL). The postoperative hemoglobin level in the delayed drainage group (91.5 +/- 7.9 g/L) was similar to that in the autotransfusion group (92.0 +/- 9.6 g/L), while that in the routine drainage group (81.3 +/- 9.9 g/L) was significantly lower. The patients in the autotransfusion group were observed to have higher body temperatures than those in the other two groups. In the routine drainage group, eight cases accepted allogenic blood transfusion, and the percentage (44.4%) was significantly higher than that in the other two groups. There were no significant between-group differences in swelling, healing qualities, and range of motion. CONCLUSIONS: Delayed postoperative drainage may reduce blood loss and the chance of allogenic blood transfusion compared with routine drainage and may also reduce the chance of postoperative fever and extra costs compared with autotransfusion. PMID- 24216255 TI - Protein/energy debt in critically ill children in the pediatric intensive care unit: acute kidney injury as a major risk factor. AB - Acute kidney injury (AKI) is common in pediatric intensive care unit (PICU) patients. In this clinical setting, the risk of protein-energy wasting is high because of the metabolic derangements of the uremic syndrome, the difficulties in nutrient needs estimation, and the possible negative effects of renal replacement therapy itself on nutrient balance. No specific guidelines on nutritional support in PICU patients with AKI are currently available. The present review is aimed at evaluating the role of AKI as a risk condition for inadequate protein/energy intake in these patients, on the basis of literature data on quantitative aspects of nutritional support in PICU. Current evidence suggests that a relevant protein/energy debt, a widely accepted concept in the literature on adult intensive care unit patients with its negative implications for patients' major outcomes, is also likely to develop in pediatric critically ill patients, and that AKI represents a key factor for its development. PMID- 24216256 TI - Effects of tea consumption on renal function in a metropolitan Chinese population: the Guangzhou biobank cohort study. AB - OBJECTIVE: Green tea consumption has been associated with many prophylactic health benefits. This study examined for the first time associations between tea consumption and renal function in a Chinese population. DESIGN AND METHODS: Cross sectional baseline data including demographics, and lifestyle and weekly consumption of green, black, and oolong tea were analyzed from 12,428 ambulatory subjects aged 50 to 85 years (67.3% female) that were randomly selected from the membership list of a community social and welfare association in Guangzhou, China. INTERVENTION: Associations between tea consumption and renal function were assessed using regression analyses to adjust for potential confounding factors. MAIN OUTCOME MEASURE: Renal function was assessed using the estimated glomerular filtration rate (eGFR) and in a subcohort of 1,910 participants using a spot urinary albumin-to-creatinine ratio. RESULTS: Six thousand eight hundred and seventy-two participants drank at least 1 type of tea. Oolong tea consumption was negatively associated with eGFR (beta-coefficient -0.019, P = .025), but in a gender-stratified analysis this was not the case. In men, black tea was positively associated with eGFR (beta-coefficient 0.037, P = .013), but not in women (beta-coefficient -0.002, P = .856). Otherwise, no statistically significant consistent associations between the measures of renal function and consumption of green tea, black tea, or oolong tea individually or total tea consumption were identified. CONCLUSION: Overall there was no clear evidence to suggest any consistent association between renal function and tea consumption in this large population-based study of older Chinese individuals. PMID- 24216257 TI - Effectiveness of a nutrition education program for the prevention and treatment of malnutrition in end-stage renal disease. AB - OBJECTIVE: In end-stage renal disease (ESRD) patients, malnutrition is mainly addressed from a pharmacological but not educational point of view. Therefore, the objective of this study was to implement a nutritional education program (NEP) and to evaluate and compare its effectiveness in the treatment and prevention of malnutrition with oral supplementation (OS)-the standard treatment in these patients. DESIGN: This study was a longitudinal, 4-month prospective study. SETTINGS: The study was conducted from January to May 2012 in the Hemodialysis Fresenius Medical Care Clinic of Murcia. SUBJECTS: One hundred twenty patients with ESRD undergoing hemodialysis were randomly assigned to a NEP or to OS. INTERVENTION: Patients assigned to the NEP group followed an educational program for 4 months that aimed to improve general nutritional knowledge and included culinary recommendations and an elaboration of balanced menus. The OS group received a nutritional supplement during the hemodialysis procedure. MAIN OUTCOME MEASURE: The main outcome measure was certain biochemical markers of nutritional and metabolic status. Nutrition knowledge was also evaluated. RESULTS: After 4 months of intervention, nutritional knowledge was increased in all patients (P < .050) after the NEP, which was reflected in a decrease in the prevalence of malnutrition, especially in this group. Creatinine clearance, total protein serum values, and other biochemical parameters improved significantly in both groups (P < .050 in all cases), although other parameters such as C-reactive protein were impaired only in the NEP group. CONCLUSION: The NEP was at least as effective as OS for preventing and even treating malnutrition in patients with chronic renal failure on hemodialysis, improving their nutritional status, which may result in a long-term decrease in the mortality and morbidity of these patients. PMID- 24216258 TI - Prevalence of vitamin D deficiency and effects of supplementation with cholecalciferol in patients with chronic kidney disease. AB - OBJECTIVE: We aimed to evaluate the vitamin D status, the effect of cholecalciferol supplementation, and the factors associated with vitamin D restoration in nondialytic patients with chronic kidney disease (CKD). DESIGN: The present study was a prospective open-label trial. SETTING: This study took place at the Seoul National University Boramae Medical Center. SUBJECTS: Patients with nondialytic CKD (estimated glomerular filtration rate [eGFR] 10-59 mL/min per 1.73 m(2)) participated in this study. INTERVENTION: Vitamin D status in 210 CKD patients was assessed and the patients with vitamin D deficiency (<30 ng/mL) were administered cholecalciferol (1,000 IU/day) for 6 months. MAIN OUTCOME MEASURE: The restoration rate of vitamin D deficiency at 3 and 6 months and the response-related factors were analyzed. RESULTS: The prevalence of vitamin D deficiency was 40.7% in CKD Stage 3, 61.5% in Stage 4, and 85.7% in Stage 5. The subgroup with vitamin D deficiency had a greater proportion of patients with diabetes, lower eGFR, and higher proteinuria. With the supplementation, 52 patients (76.5%) reached levels of 25-hydroxy vitamin D (25(OH)D) of 30 ng/mL or greater at 3 months, and the restoration of vitamin D was observed in 61 patients (89.7%) at 6 months. Lower levels of 25(OH)D and a higher amount of proteinuria at baseline were the factors associated with lower response to vitamin D supplementation. CONCLUSION: Vitamin D deficiency rate was high in nondialytic CKD patients, and the proportion increased as renal function decreased. A higher amount of proteinuria was the independent risk factor of nonresponse with supplementation. Vitamin D was replenished in most patients with cholecalciferol supplementation without any significant adverse effects. PMID- 24216259 TI - Dietary and pharmacological modification of fibroblast growth factor-23 in chronic kidney disease. AB - Increased levels of phosphorus and fibroblast growth factor-23 (FGF-23) are strong predictors of cardiovascular morbidity and mortality. From a physiological perspective and supported by some data, phosphorus is the main driver for FGF-23 secretion. Therefore, it is conceivable that interventions aiming at restriction of phosphorus uptake from the gastrointestinal tract may lower serum FGF-23 levels and improve cardiovascular risk and subsequently survival. It is not currently known to what extend phosphorus and FGF-23 are independent risk factors, and therefore both need to be targeted. However, their respective metabolisms are tightly connected. Control of phosphorus levels in chronic kidney disease (CKD) patients is attempted mainly by restriction of dietary intake and the use of phosphorus binders. In this review, it is outlined that not just the amount of dietary phosphorus intake is important but also its type (organic vs. inorganic), its source (animal vs. plant derived), and the protein-to-phosphorus ratio in the bioavailability of phosphorus from food. This qualitative aspect of diet is likely a neglected aspect of dietary counseling in CKD. However, in more advanced stages of CKD, dietary restriction of phosphorus alone is usually not sufficient to control hyperphosphatemia, and phosphorus binders are indicated. The inexpensive, calcium-containing dietary phosphorus binders are used commonly worldwide. However, they are not suitable for every patient because of the association with elevated serum calcium, increase in vascular and valvular calcification scores, and cardiovascular and all-cause mortality. The calcium content itself in these binders has recently been implicated to upregulate FGF 23. For that reason, the noncalcium, aluminum-free agents such as sevelamer and lanthanum are being advocated. However, these drugs do not have a clearly defined effect on circulating levels of FGF-23. Although it is conceivable that targeting FGF-23 may lead to improved clinical outcomes, this remains speculative. Therefore, more studies are needed to answer the question if this can be achieved with any of the phosphorus binders, or by another (additional) pharmacological intervention. PMID- 24216260 TI - Degradation of chlorophenols and alkylphenol ethoxylates, two representative textile chemicals, in water by advanced oxidation processes: the state of the art on transformation products and toxicity. AB - Advanced oxidation processes based on the generation of reactive species including hydroxyl radicals are viable options in eliminating a wide array of refractory organic contaminants in industrial effluents. The assessment of transformation products and toxicity should be, however, the critical point that would allow the overall efficiency of advanced oxidation processes to be better understood and evaluated since some transformation products could have an inhibitory effect on certain organisms. This article reviews the most recent studies on transformation products and toxicity for evaluating advanced oxidation processes in eliminating classes of compounds described as "textile chemicals" from aqueous matrices and poses questions in need of further investigation. The scope of this paper is limited to the scientific studies with two classes of textile chemicals, namely chlorophenols and alkylphenol ethoxylates, whose use in textile industry is a matter of debate due to health risks to humans and harm to the environment. The article also raises the critical question: What is the state of the art knowledge on relationships between transformation products and toxicity? PMID- 24216261 TI - Effects of low molecular weight organic acids on the immobilization of aqueous Pb(II) using phosphate rock and different crystallized hydroxyapatite. AB - Understanding the effects of low molecular weight organic acids (LMWOAs) on the transformation of Pb(II) to geochemically stable pyromorphite (PY) by apatite materials (AMs), has considerable benefits for risk assessment and remediation strategies for contaminated water and soil. In this study, we systematically investigated the immobilization of Pb(II) from aqueous solution by natural phosphate rock (PR) and different crystallized hydroxyapatite (HAp) in the absence and presence of LMWOAs (oxalic, malic and citric acids). The results indicated that the effectiveness of PR and HAp in immobilizing Pb(II) followed in descending order by HAp2 (the poorly crystallized HAp), HAp1 (the well crystallized HAp) and PR, regardlessof the presence of LMWOAs. The presence of malic and citric acids significantly decreased the immobilizationefficiency of Pb(II) by HAp1 and PR, clarifying the lower adsorption affinities of Pb(II) organic acid complexes on HAp1 and PR rather than Pb(II) ion. On thecontrary, oxalic acid could markedly enhance the removal of Pb(II) from aqueous solution by HAp1 and PR through the formation of lead oxalate, which was confirmed by FT-IR and XRDanalysis. Results also showed that LMWOAs had little promoting or inhibiting effect on the immobilization of Pb(II) by HAp2. This study suggested that the ubiquity of LMWOAs in natural environments could retard the transformation efficiency of Pb(II) to PY by AMs, especiallyin thepresenceof oxalic acid, and the poorly crystallized HAp2 had great potential to remediate Pb(II)-contaminated water and soil due to its insusceptibility to LMWOAs. PMID- 24216262 TI - Investigation of cannabis biomarkers and transformation products in waters by liquid chromatography coupled to time of flight and triple quadrupole mass spectrometry. AB - 11-Nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) is commonly selected as biomarker for the investigation of cannabis consumption through wastewater analysis. The removal efficiency of THC-COOH in wastewater treatment plants (WWTPs) has been reported to vary between 31% and 98%. Accordingly, possible transformation products (TPs) of this metabolite might be formed during treatment processes or in receiving surface water under environmental conditions. In this work, surface water was spiked with THC-COOH and subjected to hydrolysis, chlorination and photo-degradation (both ultraviolet and simulated sunlight) experiments under laboratory-controlled conditions. One hydrolysis, eight chlorination, three ultraviolet photo-degradation and seven sunlight photo degradation TPs were tentatively identified by liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (LC-QTOF MS). In a subsequent step, THC-COOH and the identified TPs were searched in wastewater samples using LC coupled to tandem mass spectrometry (LC-MS/MS) with triple quadrupole. THC-COOH was found in all influent and effluent wastewater samples analyzed, although at significant lower concentrations in the effluent samples. The removal efficiency of WWTP under study was approximately 86%. Furthermore, THC-COOH was also investigated in several surface waters, and it was detected in 50% of the samples analyzed. Regarding TPs, none were found in influent wastewater, while one hydrolysis and five photo-degradation (simulated sunlight) TPs were detected in effluent and surface waters. The most detected compound, resulting from sunlight photo-degradation, was found in 60% of surface waters analyzed. This fact illustrates the importance of investigating these TPs in the aquatic environment. PMID- 24216263 TI - Development and validation of theoretical linear solvation energy relationship models for toxicity prediction to fathead minnow (Pimephales promelas). AB - The acute toxicity predictive models are vitally important for the toxicological information used in the ecological risk assessments. In this study, we used Verhaar classification scheme to group compounds into five modes of toxic action. The quantum chemical descriptors that characterize the electron donor-acceptor property of the compounds were introduced into the theoretical linear solvation energy relationship (TLSER) models. The predictive models have relatively larger data sets, which imply that they cover a wide applicability domain (AD). All models were developed following the Organization for Economic Co-operation and Development (OECD) QSAR models development and validation guidelines. The adjusted determination coefficient (Radj(2)) and external explained variance (QEXT(2)) of the models were ranging from 0.707 to 0.903 and 0.660 to 0.858, respectively, indicating high goodness-of-fit, robustness and predictive capacity. The cavity term (McGowans volume) was the most significant descriptor in the models. Moreover, the electron donor-acceptor (E-TLSER) models are comparable to the TLSER models for the toxicity prediction to fathead minnow. Thus, the E-TLSER models developed can be used to predict acute toxicity of new compounds within the AD. PMID- 24216264 TI - Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: role of GSTM1/GSTT1 polymorphism. AB - Chronic kidney disease (CKD) of unknown etiology represents about 16% of CKD patients in Indian subcontinents and 10% worldwide. The aetiology of CKD of unknown etiology remains unclear though epidemiological studies indicate the involvement of the environmental toxins. Organochlorine pesticides (OCPs) have been detected in general population in India. It is possible that polymorphism of xenobiotic metabolizing enzymes (XMEs) may play an important role in this process. In this we intend to find out blood levels of OCPs in CKD patients of unknown etiology and to evaluate the consequence of glutathione S-transferase (GST) gene polymorphism on the same. We have assessed 270 CKD patients and 270 age-sex-matched healthy controls for this study. The blood OCP levels were analyzed by gas chromatograph. GSTM1, GSTT1 genotyping were carried out by multiplex PCR. Blood levels of HCH, endosulfan and total pesticides were significantly higher in CKD patients and negatively correlated with eGFR. The combined frequency of GSTM1(-)/GSTT1(-) genotype increased the risk of CKD by 1.8 fold as compared to healthy controls. To find out the dependence of blood OCPs level on genotype, we carried out logistic regression analysis and results revealed that GSTM1(-)/GSTT1(-) genotype associated significantly with a number of OCPs namely gamma-HCH, p,p'-DDT and total pesticides. Polymorphism of XMEs not only increased accumulation of pesticides but also aggravates kidney dysfunction as evident from significant decrease in eGFR. PMID- 24216265 TI - DNA damage in grasshoppers' larvae--comet assay in environmental approach. AB - The comet assay that provides a quantitative measure of the DNA-strand breaks may be used for assessing the 'genotoxic potential' of the environment. Young adults of Chorthippus brunneus (Orthoptera), collected at three sites in Southern Poland, differing in the level of pollution, particularly with heavy metals: Pilica (reference), Olkusz (moderately polluted) and Szopienice (heavily polluted) - were allowed to mate under laboratory conditions that were free from any pollution. Egg-pods were collected and, after diapause, brain cells from one day old larvae were used for the comet assay. We compared the level of DNA damage in the larvae originating from these sites and also measured time-dependent DNA repair after single 10min. application of H2O2 (20MUM final concentration). The DNA damage was relatively low in larval cells irrespectively of the site pollution their parents came from. However, measured comet parameters - tail DNA content (TDNA), tail length (TL), and olive tail moment (OTM) - were significantly higher in larvae originating from the Szopienice site than in those from the reference site. Incubation of cells with H2O2 resulted in significantly higher values of the comet parameters in the insects from all the study sites with the highest ones observed in the offspring of grasshoppers from Szopienice. Moreover, DNA repair, following the treatment, did not occur in the latter group. These data contribute to almost unexplored subject of genotoxic effects of environmental pollutants in insects. They are discussed in the light of the concept of adaptive strategies in energy allocation depending on the level of biotope pollution. PMID- 24216266 TI - Cross effect of temperature, pH and free ammonia on autotrophic denitrification process with sulphide as electron donor. AB - Autotrophic denitrification is a suitable technology to simultaneously remove oxidised nitrogen compounds and reduced sulphur compounds yielding nitrogen gas, sulphur and sulphate as the main products. In this work, several batch tests were conducted to investigate the cross effect of temperature, pH and free ammonia on the autotrophic denitrification. Denitrification efficiencies above 95% were achieved at 35 degrees C and pH 7.5-8.0 with maximum specific autotrophic denitrifying activities up to 188mgN2g(-1)VSSd(-1). Free ammonia did not show any effect on denitrification at concentrations up to 53mg NH3-NL(-1). Different sulphide concentrations were also tested with stoichiometric nitrite and nitrate concentrations. Sulphide inhibited denitrification at concentrations higher than 200mgS(2-)L(-1). A 50% inhibition was also found at nitrite concentrations above 48mg NO2(-)-NL(-1). The maximum specific activity decreased until a value of 25mgN2g(-1) VSSd(-1) at 232mg NO2(-)-NL(-1). The Haldane model was used to describe denitrification inhibition caused by nitrite. Kinetic parameters determined from the fitting of experimental data were rmax=176mgN2g(-1)VSSd(-1), Ks=10.7mg NO2(-)-NL(-1) and Ki=34.7mg NO2(-)-NL(-1). The obtained model allowed optimising an autotrophic denitrification process by avoiding situations of inhibition and thus obtaining higher denitrification efficiencies. PMID- 24216267 TI - Physicochemical properties and biodegradability of organically functionalized colloidal silica particles in aqueous environment. AB - Engineered sub-micron particles are being used in many technical applications, leading to an increasing introduction into the aquatic environment. Only a few studies have dealt with the biodegradability of non-functionalized organic particles. In fact the knowledge of organically surface functionalized colloids is nearly non-existent. We have investigated the biodegradability of organically surface functionalized silica (SiO2) particles bearing technically relevant groups such as amino-, carboxyl-, benzyl-, sulfonate-, chloro-, and phosphatoethyl-derivatized alkyls. Essential physicochemical properties including zeta potential, isoelectric point, morphology, surface area, porosity, surface density, and elemental composition of the particles were investigated, followed by biodegradability testing using the Closed Bottle Test (OECD 301D). None of the particles met the biodegradability threshold value of 60%. Only a slight biodegradation was revealed for SiO2-Benzyl (13.7+/-6.7%) and for SiO2-3 Chlorpropane (10.8+/-1.5%). For the other particles biodegradability was below the normal background fluctuation of 5%. The results were different of those obtained from structurally similar chemicals not being functionalized on the particle surface and from general rules of structure-biodegradation prediction of organic molecules. Therefore, our results suggest that the attachment of the organic groups heavily reduces their biodegradability, increases their residence time and possibility for adverse effects to environmental species. PMID- 24216268 TI - Effects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex. AB - The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic transmission in the prelimbic cortex during adulthood. Male Sprague Dawley rats were subjected to seven days of restraint stress on postnatal day forty-two (PND 42, adolescence). Afterward, the fear-conditioning paradigm was used to study conditioned fear extinction. Anxiety-like behavior was measured one day (PND 50) and twenty-one days (PND 70, adulthood) after stress using the elevated-plus maze and dark-light box tests, respectively. With another set of rats, excitatory synaptic transmission was analyzed with slices of the prelimbic cortex. Rats that had been stressed during adolescence and adulthood had higher anxiety-like behavior levels than did controls, while stress-induced slowing of learned fear extinction in adolescence was reversed during adulthood. As well, the field excitatory postsynaptic potentials of stressed adolescent rats had significantly lower amplitudes than those of controls, although the amplitudes were higher in adulthood. Our results demonstrate that short-term stress in adolescence induces strong effects on excitatory synaptic transmission in the prelimbic cortex and extinction of learned fear, where the effect of stress on anxiety is more persistent than on the extinction of learned fear. These data contribute to the understanding of stress neurobiology. PMID- 24216269 TI - "Ring" in the solo child singing voice. AB - OBJECTIVES/HYPOTHESIS: Listeners often describe the voices of solo child singers as being "pure" or "clear"; these terms would suggest that the voice is not only pleasant but also clearly audible. The audibility or clarity could be attributed to the presence of high-frequency partials in the sound: a "brightness" or "ring." This article aims to investigate spectrally the acoustic nature of this ring phenomenon in children's solo voices, and in particular, relating it to their "nonring" production. Additionally, this is set in the context of establishing to what extent, if any, the spectral characteristics of ring are shared with those of the singer's formant cluster associated with professional adult opera singers in the 2.5-3.5kHz region. METHODS: A group of child solo singers, acknowledged as outstanding by a singing teacher who specializes in teaching professional child singers, were recorded in a major UK concert hall performing Come unto him, all ye that labour, from the aria He shall feed his flock from The Messiah by GF Handel. Their singing was accompanied by a recording of a piano played through in-ear headphones. Sound pressure recordings were made from well within the critical distance in the hall. The singers were observed to produce notes with and without ring, and these recordings were analyzed in the frequency domain to investigate their spectra. RESULTS: The results indicate that there is evidence to suggest that ring in child solo singers is carried in two areas of the output spectrum: first in the singer's formant cluster region, centered around 4kHz, which is more than 1000Hz higher than what is observed in adults; and second in the region around 7.5-11kHz where a significant strengthening of harmonic presence is observed. A perceptual test has been carried out demonstrating that 94% of 62 listeners label a synthesized version of the calculated overall average ring spectrum for all subjects as having ring when compared with a synthesized version of the calculated overall average nonring spectrum. CONCLUSIONS: The notion of ring in the child solo voice manifests itself not only with spectral features in common with the projection peak found in adult singers but also in a higher frequency region. It is suggested that the formant cluster at around 4kHz is the children's equivalent of the singers' formant cluster; the frequency is higher than in the adult, most likely due to the smaller dimensions of the epilaryngeal tube. The frequency cluster observed as a strong peak at about 7.5-11kHz, when added to the children's singers' formant cluster, may be the key to cueing the notion of ring in the child solo voice. PMID- 24216270 TI - Statistical analysis of the reliability of acoustic and electroglottographic perturbation parameters for the detection of vocal roughness. AB - OBJECTIVES: The aim of this study was to verify whether the electroglottography (EGG) perturbation parameters could be superior indicators to traditional acoustic (Ac) measures, particularly for the detection of mild vocal roughness. METHODS: Thirty-nine participants with muscle tension dysphonia (the MTD group), 48 dysphonic participants with vocal fold lesions (the organic group), and 40 nondysphonic participants (the control group) were enrolled in the study. Based on the severity of vocal roughness, each of the two dysphonic groups was divided into mildly and severely dysphonic subgroups. The Ac and EGG signals during sustained /e:/ phonation were recorded simultaneously. The period and amplitude perturbation quotients of both signals (Ac-PPQ/-APQ and EGG-PPQ/-APQ) were calculated. The receiver operating characteristic (ROC) analyses were applied to evaluate the discriminative capabilities. RESULTS: In the analyses between the control and each of the two dysphonic groups, the values of the areas under the curve (AUC) for EGG-PPQ were significantly higher than those for Ac-PPQ. Next, the ROC analyses between the control and mildly dysphonic MTD subgroup demonstrated that the AUC values for EGG-PPQ/EGG-APQ were significantly higher than those for Ac-PPQ/Ac-APQ. In the analyses of the mildly dysphonic organic group, the AUC value for EGG-PPQ was significantly higher than that for Ac-PPQ. CONCLUSIONS: The present study demonstrated that both the period and the amplitude perturbation parameters of the EGG signals showed higher diagnostic accuracies than those of Ac signals, especially for the detection of mild vocal roughness. These results suggest that the EGG perturbation parameters could provide better information than the traditional Ac perturbations. PMID- 24216271 TI - Differences between self-assessment and external rating of voice with regard to sex characteristics, age, and attractiveness. AB - OBJECTIVES: This study investigates differences between the self-assessment and external rating of a person's voice with regard to sex characteristics, age, and attractiveness of the voice and mean fundamental frequency (F0). STUDY DESIGN: Cross-sectional study. METHODS: A group of 47 participants with a balanced sex distribution was recruited and the following data were collected: videostroboscopy, voice range profile, F0, self-assessment questionnaire (attractiveness, masculinity or femininity of voice, and appearance), Voice Handicap Index, and questionnaires to determine levels of depression and quality of life. External rating was performed by four experts and four laymen. RESULTS: In both sexes, fair to moderate significant correlations between the self assessment of masculinity (men)/femininity (women) of voice and masculinity/femininity of appearance could be found, but not between the self assessment of attractiveness of voice and appearance. In men, a statistically significant correlation was found between external ratings and self-assessment of attractiveness and, with the exception of the female rating group, of masculinity. In women, self-assessment of femininity and attractiveness of voice did not correlate to a statistically significant extent with the evaluation of the external rater. Additionally, the statistical correlation between estimated and real ages was high. CONCLUSIONS: Although the objective parameters of age and gender identification could be rated with a high degree of accuracy, subjective parameters showed significant differences between self-assessment and external rating, in particular in rating women's voices. Taking these findings into account in treatments for modifying voice could impede successful interventions. As one consequence, we recommend summarizing target agreements in detail before the treatment. PMID- 24216272 TI - Vocal fold atrophy in a Japanese tertiary medical institute: status quo of the most aged country. AB - OBJECTIVE: Voice problems in the geriatric population are increasing worldwide. Since the demographic research of geriatric voice patients in Japan, the country of the most advanced Aging Society, is missing, the authors assessed the current trend of geriatric voice patients, especially patients with presbylarynx at a tertiary medical institute of Japan. STUDY DESIGN: Retrospective study. METHODS: From a review of the medical records of newly referred patients, patients aged 65 years and older and patients with vocal fold atrophy were selected, and demographic data, questionnaires, and parameters of aerodynamic and acoustic study, and videostroboscopy were analyzed in terms of age and gender. Subsequently, the difference between patients with presbylarynx and 20 vocally healthy elderly subjects were assessed with multivariate analysis. RESULTS: Of 1157 newly referred patients seen at the Voice Outpatient Clinic between 2006 and 2012, patients aged 65 years and older accounted for 37% (428 patients): there was 7% increase during the past 7 years and the prevalence was considerably higher than any other previous reports. Vocal fold atrophy accounted for 11% (128 patients) of all patients: dysphonia in patients with vocal fold atrophy aggravated as age advanced; there was a gender difference; and multivariate analysis revealed that reflux laryngitis, chronic medical condition, and vocal abuse were risk factors of presbylarynx. CONCLUSION: In Japan, elderly dysphonic patients were prevalent and rapidly increasing in recent years. Age- and gender related differences should receive attention. Preventive approach on risk factors such as reflux laryngitis, chronic medical condition, and vocal abuse should be considered in the management of presbylarynx. PMID- 24216273 TI - Simultaneous detection of 22 toxic plant alkaloids (aconitum alkaloids, solanaceous tropane alkaloids, sophora alkaloids, strychnos alkaloids and colchicine) in human urine and herbal samples using liquid chromatography-tandem mass spectrometry. AB - A liquid chromatography-tandem mass spectrometry method for simultaneous detection of 22 toxic plant alkaloids, including aconitum alkaloids and their hydrolyzed products (aconitine, hypaconitine, mesaconitine, yunaconitine, crassicauline A, benzoylaconine, benzoylmesaconine, benzoylhypaconine, deacetylyunaconitine, deacetylcrassicauline A), solanaceous tropane alkaloids (atropine, anisodamine, scopolamine, anisodine), sophora alkaloids (matrine, sophoridine, oxymatrine, cytisine, N-methylcytisine), strychnos alkaloids (brucine, strychnine) and colchicine, in herbal and urine samples was developed and validated. Following sample preparation by liquid-liquid extraction, chromatographic separation was achieved on Eclipse XDB C8 column. Identification was based on two multiple reaction monitoring transitions and the relative ion intensity. Method selectivity was demonstrated. The limits of detection were 5ng/mL for all analytes, except 50ng/mL for cytisine. The herbal matrix effects ranged from 89% to 118%, whereas the urine matrix effects were between 91% and 109% for all analytes except cytisine (57%) and N-methylcytisine (67%). The urine extraction recovery ranged from 74% to 110% for all analytes, except cytisine (15%) and oxymatrine (30%). With the good extraction efficiency of the other major sophora alkaloids, the relatively low extraction recovery of the minor sophora alkaloids cytisine and oxymatrine did not affect identification of sophora alkaloids as a group. Carry-over was minimal at less than 0.1%. The method was successfully applied in analysis of 170 cases of suspected herbal poisoning, with aconitum alkaloids, sophora alkaloids, solanaceous tropane alkaloids, and strychnos alkaloids being detected in 53, 42, 18, and 6 cases, respectively. PMID- 24216274 TI - Preclinical pharmacokinetics, tissue distribution and excretion studies of a potential analgesics - corydaline using an ultra performance liquid chromatography-tandem mass spectrometry. AB - A rapid resolution ultra performance liquid chromatography (UPLC) coupled with electrospray ionization (ESI) mass spectrometry method was developed and validated for the quantitative analysis of corydaline in rats' plasma and various tissues for pharmacokinetic, tissue distribution and excretion studies of corydaline. The analytes were separated on an Acquity UPLC BEH C18 column (2.1mm*100mm, 1.7MUm) and detected with a triple quadrupole mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 370.0->192.0 for corydaline and 354.1->188.0 for IS, respectively. Calibration curves (1/x(2) weighted) offered satisfactory linearity (r(2)>0.9984) within 1-1000ng/mL. The accuracy and precision ranged from -7.4% to 8.5% and 3.4% to 12.8%, respectively. The absolute matrix effect (94.2-119.2%), relative matrix effect (1.7-9.6%) and recoveries (81.4-93.7%) were satisfactory in all the biological matrices examined. The assay was successfully applied to the plasma pharmacokinetics, tissue distribution and excretion studies of corydaline in rats. The pharmacokinetic parameters such as half-life (t1/2), mean residence time (MRT) and maximum concentration (Cmax) were determined. These preclinical data of corydaline would be useful for the clinical reference. PMID- 24216275 TI - Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations. AB - We investigated a novel marine fibrinolytic compound for use in thrombolytic therapy. Pharmacokinetics and the tissue distribution of this novel marine fibrinolytic compound, FGFC1(2) (fungi fibrinolytic compound 1), were investigated in Wistar rats after intravenous (IV) bolus administration of two concentrations (10 and 20mg/kg). Plasma FGFC1 and tissue extracts were measured using HPLC with UV detection. FGFC1 was detected using a C18 column with a gradient eluted mobile phase of acetonitrile-water (0.1% trifluoroacetic acid), 1.0mL/min. Chromatograms were monitored at 265nm (column temperature: 40 degrees C). Pharmacokinetic data indicate that FGFC1 fitted well to a two-compartment model. Elimination half-lives (t1/2) of FGFC1 were 21.51+/-2.17 and 23.22+/ 2.11min for 10 and 20mg/kg, respectively. AUC0-t were 412.19+/-19.09, 899.09+/ 35.86MUg/mLmin, systemic clearance (CL) was 0.023+/-0.002, 0.022+/-0.002 ((mg/kg)/(MUg/mL)/min) and the mean residence time (MRT) was 10.15+/-0.97, 9.65+/ 1.40min at 10 and 20mg/kg, respectively. No significant differences were observed in the systemic clearance and mean residence time at the tested doses, suggesting linear pharmacokinetics in rats. Tissue distribution data reveal that FGFC1 distributed rapidly in most tissues except the brain and that the highest concentration of the drug was in the liver. In the small intestine, FGFC1 initially increased and then declined, but remained comparatively high 60min after administration, suggesting that enterohepatic circulation may exist. PMID- 24216276 TI - Determination of naloxone-3-glucuronide in human plasma and urine by HILIC-MS/MS. AB - A hydrophilic interaction chromatography-tandem mass spectrometric (HILIC-MS/MS) method was developed for the direct determination of naloxone-3-glucuronide (N3G) in human plasma and urine. After a straightforward sample preparation by protein precipitation, N3G was analyzed directly without the need for hydrolysis. Chromatographic separation was performed on a HILIC column. The mobile phase was composed of acetonitrile-10mmol/L ammonium formate (86:14, v/v), with a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via positive electrospray ionisation (ESI+) source. The linear calibration range was 0.5 to 200ng/mL in plasma and 10 to 5000ng/mL in urine (r(2)>0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were below 15% and the accuracies (relative error, RE) were -7.1% to 2.8% in plasma and -1.3% to 10.3% in urine at three quality control levels. In human subjects receiving 100mg tilidine and 8mg naloxone, mean AUC0-24 of N3G was 160.93+/-52.77ng/mLh and mean Cmax was 75.33+/-25.27ng/mL. In 24-h urine samples, 8.0% of the dose was excreted in the form of N3G in urine. These results demonstrated a new method suitable for in vivo pharmacokinetic studies of N3G. PMID- 24216277 TI - Metabolic engineering of Thermoanaerobacterium saccharolyticum for n-butanol production. AB - The thermophilic anaerobe Thermoanaerobacterium saccharolyticum JW/SL-YS485 was investigated as a host for n-butanol production. A systematic approach was taken to demonstrate functionality of heterologous components of the clostridial n butanol pathway via gene expression and enzymatic activity assays in this organism. Subsequently, integration of the entire pathway in the wild-type strain resulted in n-butanol production of 0.85 g/L from 10 g/L xylose, corresponding to 21% of the theoretical maximum yield. We were unable to integrate the n-butanol pathway in strains lacking the ability to produce acetate, despite the theoretical overall redox neutrality of n-butanol formation. However, integration of the n-butanol pathway in lactate deficient strains resulted in n-butanol production of 1.05 g/L from 10 g/L xylose, corresponding to 26% of the theoretical maximum. PMID- 24216278 TI - Analysis of chlorthalidone polymorphs in raw materials and tablets and the effect of forms I and II on the dissolution properties of drug products. AB - Chlorthalidone (CTD) is an antihypertensive drug and exhibits four crystalline forms: I, II, III and IV. In this paper, the incidence of CTD polymorphs in raw materials and in tablets as well as the solubility and dissolution properties of forms I and II have been studied. Raw materials were named as A, B, C, D, and E and tablets as Reference, G1, G2 and S. Using powder X-ray diffraction and infrared spectroscopy analyses we found that A, B, E, Reference and G1 contain CTD form I; C, D and S contain predominantly form II; and G2 contain a mixture of both forms. Solubility experiments showed that form II is up to 49% more soluble than form I and dissolution studies showed a significantly effect of the polymorphism on the dissolution of CTD from tablets. Based on these results, it was concluded that only the CTD form I is acceptable for preparation of tablet form. Moreover, we proposed the polymorphic quality control of CTD raw materials and tablets. PMID- 24216279 TI - Development of novel chiral capillary electrophoresis methods for the serotonin receptor (5-HT2A) antagonist MDL 100,907 (volinanserin) and for its key intermediate compound. AB - Enantioselective capillary electrophoretic methods were elaborated for the determination of the enantiomeric purity of (R)-MDL 100,907 and its preparatively resolved key intermediate compound during the synthesis route. The pKa values of the intermediate compound and the end product determined by CE were 10.5+/-0.1 and 9.0+/-0.1, respectively. The enantiopurity of the intermediate compound can be monitored in fully protonated state by applying 15mM sulfobutylether-beta cyclodextrin at pH 5 when the peak belonging to the impurity migrates before the main component. The fact that the consecutive steps of the synthesis do not affect the enantiomeric purity was verified by the other, newly developed CE method. The enantiomers of rac-MDL 100,907 were resolved by 15mM carboxymethyl gamma-cyclodextrin at pH 3. The applicability (selectivity, LOD, LOQ, repeatability, precision and accuracy) of the methods was studied as well. PMID- 24216280 TI - Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee. AB - Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4 methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols. PMID- 24216281 TI - Liquid chromatography-tandem mass spectrometric assay for the PARP inhibitor rucaparib in plasma. AB - A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC MS/MS) assay for the poly(ADP-ribose) polymerase-1 inhibitor rucaparib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing gefitinib as internal standard. Diluted extract was directly injected into the reversed-phase chromatographic system. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 1.25 2000ng/ml calibration range with r(2)=0.9958+/-0.0012 for linear regression with quadratic weighting (n=6). Within day precisions (n=18) were 2.0-5.4%, between day (3 days; n=18) precisions 3.2-8.0% and accuracies (n=18) were 89.7-93.2%. At the lower limit of quantification (1.25ng/ml) these parameters were 9.6%, 13.7% and 85.3%, respectively. The drug was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully used to determine drug pharmacokinetics in female FVB wild type mice. PMID- 24216282 TI - Development and validation of a high-performance liquid chromatography-tandem mass spectrometry assay quantifying vemurafenib in human plasma. AB - Vemurafenib is an inhibitor of mutated serine/threonine-protein kinase B-Raf (BRAF) and is registered as Zelboraf((r)) for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. To support Therapeutic Drug Monitoring (TDM) and clinical trials, we developed and validated a method for the quantification of vemurafenib in human plasma. Additionally two LC-MS systems with different detectors were tested: the TSQ Quantum Ultra and the API3000. Human plasma samples were collected in the clinic and stored at nominally -20 degrees C. Vemurafenib was isolated from plasma by liquid-liquid extraction, separated on a C18 column with gradient elution, and analysed with triple quadrupole mass spectrometry in positive-ion mode. A stable isotope was used as internal standard for the quantification. Ranging from 1 to 100MUg/ml the assay was linear with correlation coefficients (r(2)) of 0.9985 or better. Inter assay and intra-assay accuracies were within +/-7.6% of the nominal concentration; inter-assay and intra-assay precision were within <=9.3% of the nominal concentration. In addition all results were within the acceptance criteria of the US FDA and the latest EMA guidelines for method validation for both MS detectors. In conclusion, the presented analytical method for vemurafenib in human plasma was successfully validated and the performance of the two LC-MS systems for this assay was comparable. In addition the method was successfully applied to evaluate the pharmacokinetic quantification of vemurafenib in cancer patients treated with vemurafenib. PMID- 24216283 TI - Reversed- and normal-phase liquid chromatography in quantitative structure retention-property relationships of newly synthesized seco-androstene derivatives. AB - The rational preselection of drug candidates includes also correlation between physico-chemical properties (lipophilicity, as the key one) and pharmacokinetic properties, as well as pharmacodynamic activity. Lipophilicity can be determined alternatively by chromatographic methods. Chromatographic behavior of nineteen newly synthesized derivatives of 16-cyano-16,17-seco-5-androstene has been studied by reversed-phase and normal-phase thin-layer chromatography (RP- and NP TLC). Commercial plates RP-C18-HPTLC and water-dioxane and water-acetonitrile, as well as Lux((r)) silica gel plates and toluene-dioxane and toluene-acetonitrile mixtures with different volume fractions of the solvents were used. Retention constants RM(0) and C0 for each compound were determined and correlated with (i) theoretical log P values and (ii) pharmacokinetic predictors determined in silico. Significant linear relationship was found between RP TLC retention constants, RM(0), and computational logP values as well as between NP TLC retention constants, C0, and logP. Lipophilicity values for the analytes, determined by RP TLC and NP TLC, were also correlated with computer calculated absorption constants, affinity for plasma proteins, volume of distribution and logarithm of blood-brain permeation. Significant linear relationships were obtained. These relations were further improved by introducing other regressors, as molecular size descriptors (molecular mass and/or volume) and a molecular polarity descriptor (total polar surface area). Retention parameters, RM(0) and C0, are recommended for lipophilicity expression of analyzed compounds. In silico pharmacokinetic descriptors for the analytes can be expressed as function of the lipophilicity determined by chromatographic methods, the size and the polarity of the molecules expressed as molecular mass/volume and total polar surface area. The analyzed seco-androstene derivatives have adequate lipophilicity which should provide druglikeness and good pharmacokinetic profiles and they can be recommended for further studies in which their biological activity would be examined. PMID- 24216284 TI - Factors associated with recurrent fifth metatarsal stress fracture. AB - BACKGROUND: Many surgeons agree that fifth metatarsal stress fractures have a tendency toward delayed union, nonunion, and possibly refracture. Difficulty healing seems to be correlated with fracture classification. However, refracture sometimes occurs after low-grade fracture, even long after apparent resolution. METHODS: The records of 168 consecutive cases of fifth metatarsal stress fracture (163 patients) treated by modified tension band wiring from March 2002 to June 2011 were evaluated retrospectively. Mean length of follow-up was 23.6 months (range, 10-112 months). Forty-nine cases classified as Torg III were bone grafted initially also. All enrolled patients were elite athletes. Eleven patients experienced nonunion and 18 refracture. The 11 nonunion cases were bone grafted. The 157 patients (excluding nonunion cases) were allocated to either a refracture group or a union group. Clinical features, such as age, weight, fracture classification, time to union, and reinjury history, were compared. Radiological parameters representing cavus deformity and fifth metatarsal head protrusion were compared to evaluate the influence of structural abnormalities. RESULTS: Mean group weights were significantly different (P = .041), but mean ages (P = .879), fracture grades (P = .216, P = .962), and time from surgery to rehabilitation (P = .539) were similar. No significant intergroup differences were found for talocalcaneal (TC) angle (P = .470), calcaneal pitch (CP) angle (P = .847), or talo-first metatarsal (T-MT1) angle (P = .407) on lateral radiographs; for fifth metatarsal lateral deviation (MT5-LD) angle (P = .623) on anteroposterior (AP) radiographs; or for MT5-LD angle (P = .065) on the 30-degree medial oblique radiographs. However, the mean fourth-fifth intermetatarsal (IMA4-5) angle on AP radiographs was significantly greater in the refracture group, and for Torg II cases, mean weight (P = .042), IMA4-5 angle on AP radiographs (P = .014), and MT5 LD angle (P = .043) on 30-degree medial oblique radiographs were significantly greater in the refracture group. For B2 cases (incomplete fracture and a plantar gap of 1 mm or larger), mean weight (P = .046), IMA4-5 angle on AP radiographs (P = .019), and MT5-LD angle (P = .045) on 30-degree medial oblique radiographs were significantly greater in the refracture group. All cases of refracture had a traumatic history after bone union. Refracture developed within 6 months of starting rehabilitation in 13 cases and within 3 months in 8 cases. CONCLUSION: The development of refracture after the surgical treatment of fifth metatarsal stress fractures was found to be associated with higher body mass index (BMI) and with radiological parameters (IMA4-5 on AP radiographs, MT5-LD on oblique radiographs) associated with protrusion of the fifth metatarsal head. The study indicates that patients with a protruding fifth metatarsal head and a high BMI should approach rehabilitation with care before considering a return to previous sporting activity levels. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 24216285 TI - A prospective randomized trial of everolimus-eluting stents versus bare-metal stents in octogenarians: the XIMA Trial (Xience or Vision Stents for the Management of Angina in the Elderly). AB - OBJECTIVES: The aim of this study was to determine whether drug-eluting stents (DES) are superior to bare-metal stents (BMS) in octogenarian patients with angina. BACKGROUND: Patients >=80 years of age frequently have complex coronary disease warranting DES but have a higher risk of bleeding from prolonged dual antiplatelet therapy. METHODS: This multicenter randomized trial was conducted in 22 centers in the United Kingdom and Spain. Patients >=80 years of age underwent stent placement for angina. The primary endpoint was a 1-year composite of death, myocardial infarction, cerebrovascular accident, target vessel revascularization, or major hemorrhage. RESULTS: In total, 800 patients (83.5 +/- 3.2 years of age) were randomized to BMS (n = 401) or DES (n = 399) for treatment of stable angina (32%) or acute coronary syndrome (68%). Procedural success did not differ between groups (97.7% for BMS vs. 95.4% for DES; p = 0.07). Thirty-eight percent of patients had >=2-vessel percutaneous coronary intervention, and 66% underwent complete revascularization. Patients who received BMS had shorter stent implants (24.0 +/- 13.4 mm vs. 26.6 +/- 14.3 mm; p = 0.01). Rates of dual antiplatelet therapy at 1 year were 32.2% for patients in the BMS group and 94.0% for patients in the DES group. The primary endpoint occurred in 18.7% of patients in the BMS group versus 14.3% of patients in the DES group (p = 0.09). There was no difference in death (7.2% vs. 8.5%; p = 0.50), major hemorrhage (1.7% vs. 2.3%; p = 0.61), or cerebrovascular accident (1.2% vs. 1.5%; p = 0.77). Myocardial infarction (8.7% vs. 4.3%; p = 0.01) and target vessel revascularization (7.0% vs. 2.0%; p = 0.001) occurred more often in patients in the BMS group. CONCLUSIONS: BMS and DES offer good clinical outcomes in this age group. DES were associated with a lower incidence of myocardial infarction and target vessel revascularization without increased incidence of major hemorrhage. (Xience or Vision Stent-Management of Angina in the Elderly [XIMA]; ISRCTN92243650). PMID- 24216286 TI - Pertussis epidemic despite high levels of vaccination coverage with acellular pertussis vaccine. AB - INTRODUCTION: We describe the pertussis epidemic, based only on confirmed whooping cough cases. We have analyzed data on the diagnosis, epidemiology and vaccine history in order to understand the factors that might explain the trends of the disease. METHODS: A descriptive study of the confirmed pertussis cases reported during 2011 in the Valles region (population 1,283,000). Laboratory criteria for confirmed pertussis cases include isolation of Bordetella pertussis from a clinical specimen or detection of B. pertussis by PCR in nasopharyngeal swabs. RESULTS: A total of 421 pertussis confirmed cases were reported, which was the highest incidence reported in the last decade (33 cases/100,000 people/year in 2011). The highest incidence rate was among infants less than 1 year old (448/100,000), followed by children 5-9 years old (154/100,000). Pertussis cases aged 2 months-1 year were 90% vaccinated following the current DTaP schedule for their age group in Catalonia, and cases of 5-9 years were 87% fully vaccinated with 5 doses of DTaP vaccine. There were no deaths, although 8% of cases were hospitalized. Pertussis was more severe in infants, 30% required hospitalization despite having received the vaccine doses corresponding to their age. Children of 5-9 years were most often identified as primary cases in households or school clusters. CONCLUSION: Despite high levels of vaccination coverage, pertussis circulation cannot be controlled at all. The results question the efficacy of the present immunization programmes. PMID- 24216287 TI - [Treatment of symptomatic focal nodular hyperplasia by arterial embolization]. PMID- 24216288 TI - Wind-borne dispersal of a parasitoid: the process, the model, and its validation. AB - The aphelinid parasitoid Eretmocerus hayati Zolnerowich & Rose (Hymenoptera: Aphelinidae) was recently released in Australia as a biocontrol agent against the crop pest Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae). It was found that the parasitoid can spread over several kilometers in a single generation and continue laying eggs for over a fortnight. A simple wind-advection model was fitted to emergence data from a first release between Fassifern and Kalbar, Queensland, and its predictive ability was tested against the second release near Carnarvon, Western Australia. The fitting of the model was used to develop several hypotheses about the dispersal of E. hayati, which were validated by the second release: E. hayati flies in the same direction as the wind to a distance proportional to the wind speed; this wind-borne flight takes place at any time during daylight hours; a flight is attempted every day after emergence unless there are high wind conditions during that day; and the high wind condition that will delay flight is wind speeds in excess of ?2 m/s. This model of E. hayati dispersal may be contrasted with previous models fitted for Eretmocerus species, for which dispersal was dominated by diffusion processes, and parasitoid spread was constrained to the scales of tens and hundreds of meters. PMID- 24216289 TI - Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice. AB - Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC50=25 +/- 0.38) when compared to reference compound PTER (IC50=65 +/- 0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. PMID- 24216291 TI - A sociotechnical perspective of health information technology. PMID- 24216290 TI - Lapatinib-induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. AB - INTRODUCTION: Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed. METHODS: Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor). Their in vitro and in vivo viability was examined by MTT assay, clonogenic analysis, and orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RT qPCR, immunoprecipitation assays were used to investigate the molecular mechanisms of action. RESULTS: Our data showed that nuclear factor (NF)-kappaB activation was elicited by lapatinib, independent of EGFR/HER2 inhibition, in TNBCs. Lapatinib-induced constitutive activation of NF-kappaB involved Src family kinase (SFK)-dependent p65 and IkappaBalpha phosphorylations, and rendered these cells more vulnerable to NF-kappaB inhibition by p65 small hairpin RNA. Lapatinib but not other EGFR inhibitors synergized the anti-tumor activity of proteasome inhibitors both in vitro and in vivo. Our results suggest that treatment of TNBCs with lapatinib may enhance their oncogene addiction to NF-kappaB, and thus augment the anti-tumor activity of proteasome inhibitors. CONCLUSIONS: These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients. PMID- 24216292 TI - Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing. AB - OBJECTIVE: Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer's, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. APPROACH: NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. MAIN RESULTS: The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for the successful encoding of sample phase information on more difficult DMS trials. This was validated by the delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the sample phase which facilitated task performance in the subsequent, delayed match phase, on difficult trials that required more precise encoding of sample information. SIGNIFICANCE: These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain. PMID- 24216293 TI - Bronchoalveolar lavage fluid cytokine profiles in neuroendocrine cell hyperplasia of infancy and follicular bronchiolitis. AB - BACKGROUND: Neuroendocrine Cell Hyperplasia of Infancy (NEHI) and Follicular Bronchiolitis (FB) are rare pediatric diffuse lung diseases with poorly understood pathogenesis and similar clinical presentations. We sought to determine if cellular and cytokine profiles in bronchoalveolar lavage fluid (BALF) from subjects with NEHI and FB would differ from pediatric disease controls. METHODS: BALF was obtained from forty-one subjects classified into four disease groups: NEHI, Cystic Fibrosis (CF), other airway disease controls (DC), and FB during clinically indicated procedures. BALF cellular profiles and ten cytokines were measured and values compared across groups using descriptive and nonparametric statistics. RESULTS: Significant BALF cellular and cytokine differences were seen across all groups. NEHI subjects exhibited the lowest total absolute white blood cell (WBC) levels with a higher percentage of BALF alveolar macrophages compared to controls. NEHI also had lower levels of IL-1beta, MIP 1beta and IL-8 and FB had higher levels of IL-1ra, G-CSF and VEGF compared to all groups. IL-6 was elevated in CF and FB. CONCLUSIONS: BALF cytokine and cellular profiles differed between NEHI, FB, CF and DC subjects. This pilot data suggests different and distinguishing inflammatory responses in the airway, with the least inflammatory being NEHI. These data could have diagnostic implications. PMID- 24216294 TI - Association between proinflammatory cytokines and lipid peroxidation in patients with severe dengue disease around defervescence. AB - OBJECTIVES: Proinflammatory cytokines and the oxidative stress response are reported to be involved in dengue viral disease. The present study investigated the correlation of proinflammatory cytokines and lipid peroxidation with dengue severity. METHODS: Clinical samples from 27 dengue fever (DF) cases, 30 dengue haemorrhagic fever (DHF) cases, and 24 dengue shock syndrome (DSS) cases were studied around defervescence, along with samples from 30 healthy controls. Plasma samples were analysed for tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) by ELISA and for malondialdehyde (MDA) by thiobarbituric acid assay. RESULTS: Dengue-infected individuals had significantly higher levels of TNF-alpha, IFN-gamma, and MDA in comparison to controls. The ratio of TNF-alpha to IFN-gamma was significantly higher in DHF and DSS than in DF. A TNF-alpha/IFN gamma ratio value of 5.69 around defervescence predicted DHF and DSS with moderate accuracy and thus may serve as an indicator to study dengue severity. The study observed a significant positive correlation of lipid peroxides with TNF alpha levels and the TNF-alpha/IFN-gamma ratio in severe dengue cases. CONCLUSIONS: We propose that the oxidative stress response induced by the dengue virus may trigger the inflammatory cytokine responses in dengue severity and thereby contributes to the pathogenesis of the disease; however the interplay between the oxidative response and inflammatory activity in disease virulence needs further study. PMID- 24216295 TI - Monocyte-derived dendritic cells: targets as potent antigen-presenting cells for the design of vaccines against infectious diseases. AB - Monocytes play important roles in the inflammatory response, which is essential for the innate response to pathogens. Monocytes are able to differentiate to dendritic cells (DCs) under inflammatory situations. In recent decades, the heterogeneity of monocytes and their different traffic pathways have been identified in both human and murine systems. Different monocyte subsets show distinct inflammatory cytokine profiles and differentiation potential under steady-state and inflammatory situations. We discuss the biology of monocytes, their relationship with DCs, and the potential of monocyte-derived dendritic cells (moDCs) in the design of vaccines against certain chronic infectious diseases. PMID- 24216296 TI - Reproducibility for linear and nonlinear micro-finite element simulations with density derived material properties of the human radius. AB - Finite element (FE) simulations based on high-resolution peripheral quantitative computed-tomography (HRpQCT) measurements provide an elegant and direct way to estimate bone strength. Parallel solvers for nonlinear FE simulations allow the assessment not only of the initial linear elastic behavior of the bone but also materially and geometrically nonlinear effects. The reproducibility of HRpQCT measurements, as well as their analysis of microarchitecture using linear-elastic FE simulations with a homogeneous elastic modulus has been investigated before. However, it is not clear to which extent density-derived and nonlinear FE simulations are reproducible. In this study, we introduced new mechanical indices derived from nonlinear FE simulations that describe the onset of yielding and the behavior at maximal load. Using 14 embalmed forearms that were imaged three times, we found that in general the in vitro reproducibility of the nonlinear FE simulations is as good as the reproducibility of linear FE. For the nonlinear simulations precision errors (PEs) ranged between 0.4 and 3.2% and intraclass correlation coefficients were above 0.9. In conclusion, nonlinear FE simulations with density derived material properties contain important additional information that is independent from the results of the linear simulations. PMID- 24216297 TI - Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. AB - OBJECTIVE: To assess the relative efficacy of intra-articular hyaluronic acid (IAHA) in comparison with non-steroidal anti-inflammatory drugs (NSAIDs) for knee osteoarthritis (OA). METHODS: We searched Medline, EMBASE, Google Scholar, ISI Web of Science, and Cochrane Database from inception until February 2013. Randomized controlled trials comparing HA with NSAIDs for knee OA were included if they reported at least one pain outcome. Two reviewers abstracted data and determined quality. Outcomes included pain, function, and stiffness. Random effects meta-analyses were performed. RESULTS: Five trials (712 participants) contributed to the pain analysis. Both groups showed improvement from baseline. The analysis found an effect size (ES) of -0.07 (95% CI: -0.24 to 0.10) at trial end, favoring neither treatment. There were no statistically significant differences between the groups at 4 and 12 weeks in function [ES = -0.08 (95% CI: -0.39 to 0.23)] or stiffness [ES = 0.03 (95% CI: -0.27 to 0.34)] analyses based on two trials. Injection site pain was the most common adverse event reported in the HA group, and gastrointestinal adverse events were more common in the NSAIDs group. CONCLUSION: This meta-analysis suggests that IAHA is not significantly different from continuous oral NSAIDs at 4 and 12 weeks. Our study detected no safety concerns; however, the included trials had only a short follow-up duration. Given the favorable safety profile of IAHA over NSAIDs, this result suggests that IAHA might be a viable alternative to NSAIDs for knee OA, especially for older patients at greater risk for systemic adverse events. PMID- 24216298 TI - In vitro evaluation of the resistance of a 2.0-mm titanium fixation system in the sectioned angle without continuity of the inferior border of the mandible. AB - The aim of this in vitro study was to evaluate the mechanical resistance of a 2.0 mm titanium system applied to the mandibular angle, either with or without continuity of the inferior border of the mandible. Polyurethane mandibles were used as substrates and divided into two groups: unfavourable and favourable to treatment. A single cut was made through the retromolar region, simulating an angle fracture either unfavourable or favourable to treatment. In addition, a small fragment of the inferior border of the mandible was removed in some of the mandibles, creating a discontinuity. The fragments were stabilized in accordance with the technique of Champy et al. The substrates were adapted to a universal mechanical testing machine and submitted to a constant load applied at three different points; load values were obtained at three different moments of displacement: 1mm, 2mm, and fixation failure. The value of the tip dislocation at final displacement was obtained. When the load was applied at the first molars, regardless of the side, no statistically significant difference was observed between the groups. When the load was applied at the central incisors, a statistically significant difference was observed at fixation failure in the unfavourable to treatment group, with better results in the subgroup with continuity of the inferior border of the mandible compared to the subgroup without continuity. Discontinuity of the inferior border of the mandible did not decrease the mechanical resistance of the fixation. PMID- 24216299 TI - Estrogen receptors are involved in polychlorinated biphenyl-induced apoptosis on mouse spermatocyte GC-2 cell line. AB - Polychlorinated biphenyls (PCBs) are widespread persistent environmental contaminants which have been shown to have reproductive toxicity and to disturb spermatogenesis. But the precise mechanism is not clear. A mouse pachytene spermatocyte-derived cell line, GC-2 cells were used in the present study to investigate the toxic effect of PCBs (Aroclor 1254) and explore the underlying molecular mechanism. Results showed that Aroclor 1254 inhibited cell proliferation, caused the arrest of cells in G0/G1 phase and induced apoptosis which might be partly explained by the decreased expression of Bcl-2 and cell cycle regulator cyclin D1 together with the activation of caspase-3. Besides, the treatment of Aroclor 1254 decreased the protein expression of estrogen receptor (ER)-alpha while increasing that of ERbeta. Then the administration of selective ERalpha agonist PPT partly reversed Aroclor 1254-induced alteration in Bcl-2, caspase-3 and cyclin D1 protein expression while selective ERbeta agonist DPN accelerated it. These results suggest that Aroclor 1254, working through ERalpha and ERbeta, interferes with the expression of proteins involved in the balance between cellular apoptosis and proliferation. PMID- 24216300 TI - Feasibility of a 3D human airway epithelial model to study respiratory absorption. AB - The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAirTM), cultured at the air-liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (<5%). Results indicate that the 3D human airway epithelial model used in this study is able to differentiate between substances with low and high absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans. PMID- 24216301 TI - Evaluation of simple in vitro to in vivo extrapolation approaches for environmental compounds. AB - As part of an effort to support in silico/in vitro based risk assessment, we evaluated the accuracy associated with conducting simple in vitro to in vivo extrapolation (IVIVE) for environmental compounds using available in vitro human metabolism data. The IVIVE approach was applied to a number of compounds with a wide range of properties spanning the diversity of characteristics of environmental compounds, and where possible the resulting estimates of the in vivo steady-state blood concentration were compared with estimates derived on the basis of human in vivo kinetic data. There appears to be a systematic bias in the estimation of intrinsic clearance (Clint) from in vitro versus in vivo data, with in vitro based estimates underestimating in vivo clearance for small values of Clint but with the opposite relationship at large values of Clint. Nevertheless, the resulting estimates of Css were in good agreement. The chief drawback of the simple approach used in this study, which performs the IVIVE prediction for the parent compound only, is that it is not applicable for toxicity associated with a metabolite. PMID- 24216302 TI - [Prenatal management of isolated IUGR]. AB - OBJECTIVE: To evaluate the performance of different antenatal tools for the monitoring of fetuses with isolated intrauterine growth restriction (IUGR). To define the prenatal management of IUGR and indications for delivery before and after 32 weeks of gestation. METHOD: PubMed, Embase and the Cochrane databases were searched using the keywords "IUGR", "fetal growth restriction", "cardiotocography", "amniotic fluid", "ultrasound assessment", "biophysical profile", "Doppler ultrasonography", "randomized trial", "meta-analysis". These terms were also combined together. RESULTS: Fetal monitoring of isolated IUGR should be based on the combined use of fetal heart rate (FHR) and ultrasound Doppler. The use of computerized FHR, with short-term variability (STV) measurement allows longitudinal monitoring and provides objective values upon which to decide very premature delivery (LE3). The use of umbilical Doppler is associated with a decrease in perinatal morbidity, especially in IUGR (LE1). It should be the first-line mean for the monitoring of SGA and IUGR fetuses (LE1). The additional use of cerebral Doppler is associated with a better predictive value for a poor perinatal outcome than the umbilical Doppler alone (LE3). Therefore, cerebral Doppler should be used in fetuses with IUGR, whether the umbilical Doppler is normal or not. As morbidity and mortality is increased in IUGR with pathological ductus venosus, the use of this Doppler should be considered in the monitoring of IUGR at before 32 weeks (professional consensus). Routine hospitalization is not mandatory for the monitoring of fetuses with IUGR/SGA. However, tertiary referral is advisable in cases of severe IUGR at between 26 to 32 weeks (professional consensus). The decision for delivery cannot be standardized and should be based on the combined analysis of gestational age, fetal heart rate analysis and Doppler study (professional consensus). CONCLUSION: Monitoring of fetuses with IUGR and decision for delivery should be based on the combined analysis of gestational age, fetal heart rate analysis and Doppler study before 32 weeks, this should ideally be performed by the association of computerized FHR and arterial and venous Doppler. PMID- 24216303 TI - [Prevention of IUGR]. AB - AIM: Prevention of intrauterine growth restriction (IUGR) should be addressed before conception ideally for all women, or at least for those with a medical risk factor or with a history of poor perinatal outcome or obstetrical complication. The aim of this section is to assess available evidence on IUGR prevention and elaborate clinical guidelines. PATIENTS AND METHOD: Bibliographic research on PubMed and Cochrane Database. RESULTS: Maternal age above 40 increases the risk of IUGR (Experts opinion). Encouraging women to start pregnancy when their Body Mass Index (BMI) is between extremes (grade B) and aiming for recommended weight gain according to their preconceptional BMI (professional consensus) reduce the risk of IUGR. When possible, avoiding multiple pregnancies (grade A), stabilizing chronic diseases that can influence placenta vascularization (professional consensus), stopping smoking as soon as possible before or at the beginning of pregnancy (grade A), limiting hypoglycemia during pregnancy (grade C) and tolerating mild maternal hypertension throughout pregnancy (professional consensus) also limit the risks of IUGR. In women with a prior preeclampsia<34 WG or an IUGR <5th centile due to placental dysfunction, aspirin given ideally in the second part of the day (grade B) can be a useful option and should be started before 16 WG (grade A). CONCLUSIONS: There are few methods to prevent IUGR, and some simple recommendations seem useful. Aspirin seems a useful option in women identified as at risk of IUGR. More research is needed on prevention of IUGR. PMID- 24216304 TI - [Termination of pregnancy and palliative care in case of vascular intra-uterine growth retardation]. AB - OBJECTIVE: Discuss the place of medical termination of pregnancy and palliative care in case of vascular intra uterine growth retardation. METHODS: Bibliographic review using the Medline and PubMed databases and the guidelines of the international professional societies. RESULTS: The prognostic evaluation in case of IUGR is essential. It is based on several criteria, including gestational age and ultrasound (estimated fetal weight and Doppler). In some situations, postnatal prognosis may seem so pejorative that absence of active care can be decided with the parents. The choice can then be focused on a decision not to proceed with fetal extraction while Doppler or fetal heart rate abnormalities could justify it and "wait" for spontaneous fetal death or have a more active attitude of medical termination of pregnancy (TOP) with or without feticide or palliative care after birth. In some cases, IUGR is accompanied by maternal complications such as preeclampsia. The severity of the maternal disease may sometimes justify a termination of pregnancy for maternal rescue. That either maternal or fetal indication, these situations are often difficult to manage because of the difficulty in establishing fetal prognosis, particularly when the maternal condition requires urgent decision. CONCLUSION: In these difficult situations, ultrasound assessment must be conducted by a senior and the discussion should always be multidisciplinary. If TOP is requested by the parents, it must be discussed in a multidisciplinary center for prenatal diagnosis in accordance with French law. Maternal emergency is the only derogatory status. PMID- 24216305 TI - [Prevalence, risk factors, maternal and fetal morbidity and mortality of intrauterine growth restriction and small-for-gestational age]. AB - OBJECTIVES: To assess the prevalence of fetal growth restriction (FGR) and small for gestational age (SGA) in France and other populations, the risk factors associated with SGA and its impact on fetal well-being and obstetrical outcome. METHODS: A critical review of studies identified from searches of PubMed and the Cochrane libraries using the following keywords "intra-uterine growth retardation", "intra-uterine growth restriction", "small for gestational age", "epidemiology", "risk factors", "pregnancy outcome", "maternal morbidity", "perinatal death". RESULTS: Studies of FGR use multiple definitions, both with respect to cutoffs for defining restricted growth as well as growth norms; however the most common definition for epidemiological research was SGA using a birthweight less than the 10 th percentile. Following this definition, SGA births accounted for 8.9% of all live births in 2010 in France. Major risk factors identified in the literature were previous SGA birth (4 fold increase in risk) (LE2), diabetes and vascular diseases (5 fold) (LE3), chronic hypertension (2 fold) (LE2), preeclampsia (5 to 12 fold according to severity) (LE2), pregnancy induced hypertension (2 fold) (LE2), smoking (2-3 fold) (LE2), drug and alcohol use (2-4 fold) (LE2), maternal age over 35 (3 fold) (LE2) and ethnic origin (2-3 fold for African-American or Asian origins) (LE2). Other risk factors with adjusted odds ratios around 1.5 were primiparity (LE2), multiple pregnancy (but only starting at 30 weeks of gestation) (LE2), socioeconomic disadvantage (LE2) and body mass index (BMI<18.5 kg/m(2)) (LE2) SGA is associated with a four-fold increased risk of stillbirth (LE2) as well as higher rates of cesarean and induced labor before 37 weeks. CONCLUSIONS: FGR is a complication of pregnancy with adverse consequences for fetal wellbeing. Sociodemographic and clinical risk factors can help to identify pregnant women at risk for this complication. PMID- 24216306 TI - [Intra-uterine growth retardation: guidelines for clinical practice--Short text]. PMID- 24216307 TI - Two nuclear export signals of Cdc6 are differentially associated with CDK mediated phosphorylation residues for cytoplasmic translocation. AB - Cdc6 is cleaved at residues 442 and 290 by caspase-3 during apoptosis producing p49-tCdc6 and p32-tCdc6, respectively. While p32-tCdc6 is unable to translocate into the cytoplasm, p49-tCdc6 retains cytoplasmic translocation activity, but it has a lower efficiency than wild-type Cdc6. We hypothesized that a novel nuclear export signal (NES) sequence exists between amino acids 290 and 442. Cdc6 contains a novel NES in the region of amino acids 300-315 (NES2) that shares sequence similarity with NES1 at residues 462-476. In mutant versions of Cdc6, we replaced leucine with alanine in NES1 and NES2 and co-expressed the mutant constructs with cyclin A. We observed that the cytoplasmic translocation of these mutants was reduced in comparison to wild-type Cdc6. Moreover, the cytoplasmic translocation of a mutant in which all four leucine residues were mutated to alanine was significantly inhibited in comparison to the translocation of wild type Cdc6. The Crm1 binding activities of Cdc6 NES mutants were consistent with the efficiency of its cytoplasmic translocation. Further studies have revealed that L468 and L470 of NES1 are required for cytoplasmic translocation of Cdc6 phosphorylated at S74, while L311 and L313 of NES2 accelerate the cytoplasmic translocation of Cdc6 phosphorylated at S54. These results suggest that the two NESs of Cdc6 work cooperatively and distinctly for the cytoplasmic translocation of Cdc6 phosphorylated at S74 and S54 by cyclin A/Cdk2. PMID- 24216308 TI - Effect of Mg and Si co-substitution on microstructure and strength of tricalcium phosphate ceramics. AB - Magnesium and silicon co-doped tricalcium phosphate (TCP) ceramics with compositions corresponding to 0, 5 and 10wt% CaMg(SiO3)2 in the system Ca3(PO4)2 CaMg(SiO3)2 were obtained by conventional sintering of compacted mixtures of Ca3(PO4)2, MgO, SiO2 and CaCO3 powders at temperatures between 1100 and 1450 degrees C. Microstructural analyses were performed by X-ray diffraction and field emission scanning electron microscopy with energy dispersive spectroscopy. Major phases in the obtained ceramics were beta- or alpha+beta-tricalcium phosphate containing Mg and Si in solid solution. Certain amounts of liquid were formed during sintering depending on composition and temperature. There were found significant differences in distributions of strength determined by the diametral compression of disc tests (DCDT). Failure strengths were controlled by microstructural defects associated with phase development. Mg and Si additions were found to be effective to improve densification and associated strength of TCP bioceramics due to the enhancement of sintering by the low viscosity liquids formed. The highest density and strength were obtained for the TCP ceramic containing 5wt% CaMg(SiO3)2 sintered at 1300 degrees C. Cracking and porosity increased at higher temperatures due to grain growth and swelling. PMID- 24216309 TI - A biomimetic approach for designing stent-graft structures: Caterpillar cuticle as design model. AB - Stent-graft (SG) induced biomechanical mismatch at the aortic repair site forms the major reason behind postoperative hemodynamic complications. These complications arise from mismatched radial compliance and stiffness property of repair device relative to native aortic mechanics. The inability of an exoskeleton SG design (an externally stented rigid polyester graft) to achieve optimum balance between structural robustness and flexibility constrains its biomechanical performance limits. Therefore, a new SG design capable of dynamically controlling its stiffness and flexibility has been proposed in this study. The new design is adopted from the segmented hydroskeleton structure of a caterpillar cuticle and comprises of high performance polymeric filaments constructed in a segmented knit architecture. Initially, conceptual design models of caterpillar and SG were developed and later translated into an experimental SG prototype. The in-vitro biomechanical evaluation (compliance, bending moment, migration intensity, and viscoelasticity) revealed significantly better performance of hydroskeleton structure than a commercial SG device (Zenith(TM) Flex SG) and woven Dacron((r)) graft-prosthesis. Structural segmentation improved the biomechanical behaviour of new SG by inducing a three dimensional volumetric expansion property when the SG was subjected to hoop stresses. Interestingly, this behaviour matches the orthotropic elastic property of native aorta and hence proposes segmented hydroskeleton structures as promising design approach for future aortic repair devices. PMID- 24216310 TI - Fatigue behavior of Ti6Al4V and 316 LVM blasted with ceramic particles of interest for medical devices. AB - Grit blasting is used as a cost-effective method to increase the surface roughness of metallic biomaterials, as Ti6Al4V and 316 LVM, to enhance the osteointegration, fixation and stability of implants. Samples of these two alloys were blasted by using alumina and zirconia particles, yielding rough (up to Ra~8MUm) and nearly smooth (up to Ra~1MUm) surfaces, respectively. In this work, we investigate the sub-surface induced microstructural effects and its correlation with the mechanical properties, with special emphasis in the fatigue behavior. Blasting with zirconia particles increases the fatigue resistance whereas the opposite effect is observed using alumina ones. As in a conventional shot penning process, the use of rounded zirconia particles for blasting led to the development of residual compressive stresses at the surface layer, without zones of stress concentrators. Alumina particles are harder and have an angular shape, which confers a higher capability to abrade the surface, but also a high rate of breaking down on impact. The higher roughness and the presence of a high amount of embedded alumina particles make the blasted alloy prone to crack nucleation. Interestingly, the beneficial or detrimental role of blasting is more intense for the Ti6Al4V alloy than for the 316 steel. It is proposed that this behavior is related to their different strain hardening exponents and the higher mass fraction of particles contaminating the surface. The low value of this exponent for the Ti6Al4V alloy justifies the expected low sub-surface hardening during the severe plastic deformation, enhancing its capability to soft during cyclic loading. PMID- 24216312 TI - Nitrogen washout/washin, helium dilution, and computed tomography in the assessment of end-expiratory lung volume. PMID- 24216311 TI - Failure mode analysis of silicon-based intracortical microelectrode arrays in non human primates. AB - OBJECTIVE: Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. APPROACH: Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. MAIN RESULTS: Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. SIGNIFICANCE: This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade. PMID- 24216313 TI - Do risky friends change the efficacy of a primary care brief intervention for adolescent alcohol use? AB - PURPOSE: To determine if peer risk (having friends who drink or approve of drinking) modifies the effects of a computer-facilitated screening and provider brief advice (cSBA) intervention on adolescent alcohol use. METHODS: We assessed the intervention effect using logistic regression modeling with generalized estimating equations on a sample of 2,092 adolescents. Effect modification by peer risk was analyzed separately for alcohol initiation (drinking at follow-up in baseline nondrinkers) and cessation (no drinking at follow-up in baseline drinkers) by testing an interaction term (treatment condition by peer risk). Interpretation of the interaction effect was further clarified by subsequent stratification by peer risk. RESULTS: The intervention effect on alcohol cessation was significantly greater among those with peer risk (adjusted relative risk ratios; risk 1.44, 1.18-1.76 vs. no risk .98, .41-2.36) at 3 months' follow up. There was no such finding for alcohol initiation. CONCLUSIONS: Alcohol screening and brief provider counseling may differentially benefit adolescent drinkers with drinking friends. PMID- 24216314 TI - Nrf2 signaling is impaired in the aging RPE given an oxidative insult. AB - Age-related macular degeneration (AMD) represents the leading cause of blindness in the elderly, yet no definitive therapy exists for early, dry disease. Several lines of evidence have implicated oxidative stress-induced damage to the retinal pigment epithelium (RPE) in the pathogenesis of AMD, suggesting that the aging RPE may exhibit increased susceptibility to cell damage induced by exogenous stressors. The transcription factor Nrf2 serves as the master regulator of a highly coordinated antioxidant response in virtually all cell types. We compared Nrf2 signaling in the RPE of young (2 months) and old (15 months) mice under unstressed and stressed (sodium iodate) conditions. The aging RPE expressed higher levels of the Nrf2 target genes NQO1, GCLM, and HO1 compared with the RPE of younger mice under unstressed conditions, suggesting an age-related increase in basal oxidative stress. Moreover, the RPE of older mice demonstrated impaired induction of the protective Nrf2 pathway following oxidative stress induced with sodium iodate. The RPE of old mice exposed to sodium iodate also exhibited higher levels of superoxide anion and malondialdehyde than young mice, suggesting inadequate protection against oxidative damage. Induction of Nrf2 signaling in response to sodium iodate was partially restored in the RPE of aging mice with genetic rescue, using conditional knockdown of the Nrf2 negative regulator Keap1 (Tam-Cre; Keap1loxP) compared to Keap1loxP mice. These data indicate that the aging RPE is vulnerable to oxidative damage due to impaired Nrf2 signaling, and that Nrf2 signaling is a promising target for novel pharmacologic or genetic therapeutic strategies. PMID- 24216315 TI - Expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma: low p27 expression predicts poor prognosis. AB - Prognosis of eyelid sebaceous gland carcinoma is largely unpredictable and there are few practically available markers for predicting patients' prognosis. Dysregulation of cell cycle progression is strongly associated with the development of cancer and the cancer prognosis. We investigated the expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma and estimate their value as prognostic predictors. Forty-three cases of eyelid sebaceous gland carcinoma were included in this study. Immunohistochemistry for the p53, p21, p27, cyclin E, p16, cyclin D1, and phosphorylated Rb (pRb) proteins was performed using archival paraffin blocks. Correlations between clinical features and protein expression were evaluated statistically. Nine patients showed lymph node or distant metastasis, and the remaining patients showed localized disease. High expression of p21, p27, cyclin E, and p16 was found in the majority of tumor cell nuclei, whereas these proteins were rarely expressed in the normal sebaceous glands. However, pRb was focally lost in a subset of cases. Patients showing diffuse p27 expression developed metastasis less commonly than those with negative or focal p27 expression (log-rank test, p = 0.008). Aberrant expression of cell cycle regulatory proteins was observed in eyelid sebaceous gland carcinoma, suggesting that cell cycle dysregulation is involved in the pathogenesis of this tumor. Decreased p27 expression is a predictive biomarker of an unfavorable prognosis of eyelid sebaceous gland carcinoma. PMID- 24216316 TI - Long-term follow-up of stentless prosthesis. AB - BACKGROUND: Stentless prostheses have an interesting hemodynamic performance when compared to stented prostheses and are recommended in cases of small aortic annulus. MATERIALS AND METHODS: From January 1996 to January 2004, 138 patients suffering from aortic disease, underwent aortic valve replacement. * Group A: 93 patients underwent stentless aortic valve implantation [stentless Biocor (Biocor Industria e Pesguisa Ltda, Belo Horizonte, Brazil) and stentless Sorin (Sorin Group, Saluggia, Italy)]. * Group B: 45 patients underwent stented aortic valve implantation (stented Biocor). Patients were assessed by clinical evaluation and echocardiography after a mean follow up of 124.5 +/- 58.2 months. RESULTS: There was a significant difference in terms of time of extracorporeal circulation and aortic cross clamp. The actuarial survival at 4, 8, 12, and 15 years is 77%, 50%, 21%, and 18%, respectively. Freedom from reoperation at 4, 8, 12, and 14 years was 92%, 83%, 73%, and 63%, respectively. Freedom from all events, death, and reoperation at 4, 8, 12, and 14 years was 70%, 39%, 13%, and 8%, respectively. There is no statistical difference among the two groups in terms of actuarial survival, freedom from reoperation, and freedom from re-hospitalization for prosthesis-related causes. DISCUSSION: There was a significantly higher incidence of pacemaker implantation in Group A and the causes are not known. The rate of freedom from reoperation is high in both groups for the patients who remained alive. There was no statistical difference about prosthesis dysfunction between the two groups. The higher incidence of death in Group A cannot be explained by causes related to the prosthesis because there is no difference in terms of causes of death. Rates of reoperation did not differ between the two groups. CONCLUSIONS: The results obtained with stentless prostheses are encouraging even in long-term follow-up. PMID- 24216317 TI - Preloading with atorvastatin before percutaneous coronary intervention in statin naive Asian patients with non-ST elevation acute coronary syndromes: A randomized study. AB - BACKGROUND: Data on atorvastatin pretreatment in Asian patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) are limited. However, there have been studies in other populations in Asia which demonstrated that statins can reduce the risk of periprocedural myocardial infarction (MI). METHODS AND RESULTS: Statin-naive patients with non-ST-segment elevation (NSTE)-ACS scheduled for PCI were randomized to usual care or atorvastatin preloading groups. All patients received usual care including atorvastatin 40 mg/day. The atorvastatin group received atorvastatin 80 mg 12 h and 40 mg 2 h pre-PCI. Of 499 patients randomized, 247 were assigned to atorvastatin preloading. Following coronary angiography, 335 patients (163 atorvastatin) received PCI. During the 30 days post-PCI, major adverse cardiac events (death, MI, and target vessel revascularization) occurred in 24 (15%) atorvastatin and 27 (16%) usual care patients (p=NS). Post hoc analyses showed that at 8 h post-PCI, 3.82% of the atorvastatin group and 7.22% of the usual care group had a post-procedural creatine kinase-myocardial band (CK-MB) above 3 times the upper limit of normal (p=0.27) and at 24 h post-PCI, the rate was 7.64% versus 9.47% (p=1.0). Safety profile suggests that high-dose atorvastatin (40 mg) for up to 1 month, in conjunction with usual care, is relatively safe and well tolerated. CONCLUSIONS: This study of statin-naive Korean and Chinese patients with NSTE-ACS who received additional atorvastatin loading doses of 80 mg at 12 h, and 40 mg at 2 h, pre-PCI did not find a beneficial effect compared with usual post-PCI atorvastatin 40 mg/day treatment. Atorvastatin was found to be well tolerated in Asian patients with NSTE-ACS undergoing PCI. Results of the current study merit further investigation of the early use of statins in patients with NSTE-ACS to delineate patient subgroups who may benefit from this therapy. PMID- 24216318 TI - Lipoteichoic acid of Streptococcus mutans interacts with Toll-like receptor 2 through the lipid moiety for induction of inflammatory mediators in murine macrophages. AB - Streptococcus mutans is a pathogenic Gram-positive bacterium that is closely associated with dental caries and subsequent pulpal inflammation. Although lipoteichoic acid (LTA) is considered a major virulence factor of Gram-positive bacteria, little is known about the innate immunity to S. mutans LTA. In this study, we purified LTA from S. mutans (Sm.LTA) through n-butanol extraction, hydrophobic interaction column chromatography, and ion-exchange column chromatography to investigate its immunological properties using murine macrophages. The Sm.LTA preparation had no detectable contamination with endotoxins, proteins, or nucleic acids. Upon exposure to Sm.LTA, the murine macrophage cell-line RAW 264.7 cells produced TNF-alpha and nitric oxide (NO) in a dose-dependent manner. Sm.LTA preferentially bound to and activated CHO/CD14/TLR2 cells rather than CHO/CD14/TLR4 cells, which are stable transfectants expressing CD14 and TLR2 or CD14 and TLR4, respectively. Sm.LTA could not induce TNF-alpha or NO production in macrophages derived from TLR2 deficient mice whereas it dose-dependently induced those inflammatory mediators in wild-type macrophages. TLR2-dependent induction of NO by Sm.LTA was also confirmed in RAW 264.7 cells using specific antibodies blocking TLR2. Furthermore, Sm.LTA deacylated by alkaline hydrolysis neither stimulated TLR2 nor induced TNF-alpha or NO production, suggesting that Sm.LTA lipid moieties are crucial for the immuno-stimulatory activity of Sm.LTA. Unlike Staphylococcus aureus LTA, which has potent immuno-stimulating activity, Sm.LTA showed a modest induction of NO production comparable to LTAs of other oral bacteria Enterococcus faecalis and Lactobacillus plantarum. In conclusion, our results suggest that the Sm.LTA interacts with TLR2 through the lipid moiety for the induction of inflammatory mediators in macrophages. PMID- 24216319 TI - Prevalence of undiagnosed diabetes among non-pregnant women of reproductive age in the United States, 1999-2010. AB - Undiagnosed diabetes has particularly harmful consequences among women of reproductive age. We assessed the prevalence of undiagnosed diabetes among non pregnant women of reproductive age. In our data 30 women had A1C >= 6.5 and 28 had FPG >= 126 mg/dl values suggesting approximately 300,000 women of reproductive age nationwide may have undiagnosed diabetes. PMID- 24216320 TI - Current status and future prospects of toxicogenomics in drug discovery. AB - In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput techniques integrated with well-designed analytical tools at all stages of DDD (termed 'next-generation DDD') could be a possible approach to obtaining new drug approval by cutting costs as well as ensuring the highest level of patient safety. In this review, we describe the various components of holistic toxicogenomics with examples of applications, and discuss the various analytical tools and platforms to illustrate the current status and prospects of next-generation DDD. PMID- 24216322 TI - Soluble P-selectin: the next step. PMID- 24216323 TI - Fulminant encephalitis associated with a vaccine strain of rubella virus. AB - Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barre syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in Sao Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain. PMID- 24216324 TI - Combined effect of temperature and controlled atmosphere on storage and shelf life of 'Rocha' pear treated with 1-methylcyclopropene. AB - The combination of temperature and atmosphere composition for storage of Pyrus communis L. 'Rocha' treated with 1-methylcyclopropene was investigated. Fruits treated with 312 nl l(-1) 1-methylcyclopropene were stored at 0 C and 2.5 C in air and controlled atmosphere (CA) (3.04 kPa O2+ 0.91 kPa CO2). Fruits were removed from storage after 14, 26 and 35 weeks, transferred to shelf-life at approximately 22 C and assessed for ripening and quality, symptoms of superficial scald and internal browning and the accumulation of biochemical compounds related to scald after 0, 1 and 2 weeks. Superficial scald occurred only in fruits stored for 35 weeks in air at 2.5 C. Levels of conjugated trienols and alpha-farnesene increased during the first 26 weeks in storage, remaining constant thereafter. During shelf-life, conjugated trienols were higher in fruits stored in air at 2.5 C. Internal browning developed in shelf-life after 26 weeks at 2.5 C. Pears in air at 2.5 C were not able to stand a 2-week shelf-life after 35 weeks of storage, while fruits stored at 0 C under CA ripened slowly after the same storage period. The retention of firmness during shelf-life of 1 methylcyclopropene-treated 'Rocha' pear can be overcome by elevating the storage temperature from 0 C to 2.5 C, but CA is a required complement to avoid excessive softening after long-term storage. The ratio carotenoid/chlorophyll increased during storage and shelf-life, as plastids senesced. CA reduced the rate of chlorophyll loss during the first 14 weeks in storage, but its effect was reduced afterwards. 'Rocha' pear treated with 1-methylcyclopropene had a similar post harvest behaviour during long-term storage at 0 C in air or at 2.5 C under CA. PMID- 24216325 TI - Ontogeny and stand condition influence the dispersal behavior of a defoliating specialist caterpillar. AB - A 4-yr field study was carried out to study the dispersal behavior of young larvae of the eastern spruce budworm (Choristoneura fumiferana Clemens) (Lepidoptera: Tortricidae) within and between crowns of balsam fir (Abies balsamea (L.) Miller), through the peak to decline of an outbreak. Newly hatched neonates, searching for overwintering sites in the fall, were frequently captured in sticky traps as they dispersed via "ballooning" (on silken threads) between and within tree crowns. A relatively small proportion of neonates were also captured on sticky tapes as they walked down the trunk toward the lower crown, where most larvae overwinter. In the spring, second-instar larvae (L2) searching for feeding sites also ballooned within and between trees, but were also frequently captured on traps on all crown levels as they walked up trunks. Over the course of our study, defoliation in our study trees increased, and current year shoot availability decreased significantly, perhaps influencing L2 in search of food to disperse more frequently among hosts via ballooning. Results of our study suggest that the foraging priorities of neonates and L2 significantly influence larval dispersal behaviors and that spruce budworm larvae may vary behaviors in response to changing host condition during an outbreak. PMID- 24216321 TI - Modelling three-dimensional protein structures for applications in drug design. AB - A structural perspective of drug target and anti-target proteins, and their molecular interactions with biologically active molecules, largely advances many areas of drug discovery, including target validation, hit and lead finding and lead optimisation. In the absence of experimental 3D structures, protein structure prediction often offers a suitable alternative to facilitate structure based studies. This review outlines recent methodical advances in homology modelling, with a focus on those techniques that necessitate consideration of ligand binding. In this context, model quality estimation deserves special attention because the accuracy and reliability of different structure prediction techniques vary considerably, and the quality of a model ultimately determines its usefulness for structure-based drug discovery. Examples of G-protein-coupled receptors (GPCRs) and ADMET-related proteins were selected to illustrate recent progress and current limitations of protein structure prediction. Basic guidelines for good modelling practice are also provided. PMID- 24216326 TI - Dietary fiber intake reduces risk for colorectal adenoma: a meta-analysis. AB - BACKGROUND & AIMS: Reports on the association between dietary fiber intake and risk of colorectal adenoma (CRA), the precursor of colorectal cancer, have been inconsistent. We conducted a meta-analysis of case-control and cohort studies to analyze this association. METHODS: We searched the MEDLINE and EMBASE databases to identify relevant studies published through July 2013. A random-effects model was used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for associations between fiber intake and CRA risk. Heterogeneity among studies was assessed using the Cochran Q and I(2) statistics. RESULTS: Our meta analysis included 20 studies involving 10,948 subjects with CRA. The SRRs of CRA for total dietary fiber were 0.72 (95% CI, 0.63-0.83) in a high- vs low-intake analysis and 0.91 (95% CI, 0.87-0.95) per 10-g/day increase in fiber intake in a dose-response model. Subgroup analyses indicated a significant inverse association between total fiber intake and CRA risk in case-control studies (SRR, 0.66; 95% CI, 0.56-0.77), but not in cohort studies (SRR, 0.92; 95% CI, 0.76 1.10). The SRRs of CRA were 0.84 for fruit fiber (95% CI, 0.76-0.94; n = 6 studies), 0.93 for vegetable fiber (95% CI, 0.84-1.04; n = 6 studies), and 0.76 for cereal fiber (95% CI, 0.62-0.92; n = 9 studies) in high- vs low-intake analyses. CONCLUSIONS: Our findings support the hypothesis that high dietary fiber intake is associated inversely with CRA risk. Further studies with prospective designs that use validated questionnaires and control for important confounders are warranted. PMID- 24216327 TI - Fiberoptic confocal raman spectroscopy for real-time in vivo diagnosis of dysplasia in Barrett's esophagus. PMID- 24216328 TI - Multilocus sequence typing of Campylobacter jejuni and Campylobacter coli strains isolated from environmental waters in the Mediterranean area. AB - Campylobacter jejuni and Campylobacter coli are important animal-related waterborne pathogens that are distributed worldwide. To further understand Campylobacter populations in water from the Mediterranean area, the genetic diversity of environmental strains was analyzed using multilocus sequence typing (MLST). MLST was also used to determine the potential geographical differences between these bacterial strains and other campylobacters isolated worldwide. The typing study was conducted using 58 strains isolated from the Llobregat river and other water sources, such as urban sewage, animal wastewater and clinical samples. Thirty-nine different sequence types were obtained; eight of these sequences were described for the first time in this study, suggesting the presence of local strains. The identified C. jejuni strains were the most diverse population, whereas the identified C. coli strains showed a high clonal structure, which clustered most of the sequence types into a few clonal complexes. The strains were not exclusively related to specific water sources. However, comparing the identified strains with an international database showed that most of the Mediterranean strains that were exclusively isolated from environmental waters have previously been isolated from similar sources, particularly those obtained from river water. Additional studies, including those in different geographical areas using a wide range of Campylobacter sources, are required to improve the global knowledge concerning Campylobacter dissemination in the environment. PMID- 24216330 TI - The Durban declaration. PMID- 24216329 TI - The glial-neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats. AB - This study examined the role of the glial-neuronal G protein-coupled receptor kinase 2 (GRK2) pathway in the development of trigeminal neuropathic pain. Male Sprague Dawley rats, weighing 220 to 240 g, were anesthetized with ketamine (0.2 g/kg) and xylazine (0.02 g/kg). Under anesthesia, the left lower second molar was extracted, followed by the placement of a mini-dental implant to intentionally injure the inferior alveolar nerve. This injury produced mechanical allodynia along with the downregulation of neuronal GRK2 expression in the medullary dorsal horn. On the other hand, early intracisternal treatment with MDL28170, a calpain inhibitor, produced prolonged antiallodynic effects and blocked this downregulation of neuronal GRK2 expression. The intracisternal infusion of minocycline, a microglia inhibitor, and l-alpha-aminoadipic acid, an astrocytic specific inhibitor, also blocked the induced mechanical allodynia and downregulated neuronal GRK2 expression, respectively. Double immunofluorescence showed that the interleukin (IL)-1beta and IL-1R signals colocalize with the astrocytes and neurons, respectively, in the medullary dorsal horn following an inferior alveolar nerve injury. In addition, the intracisternal infusion of an IL 1 receptor antagonist also produced antiallodynic effects and blocked the downregulation of neuronal GRK2 expression. These results suggest that the glial neuronal GRK2 pathway is a potentially important new target for treating neuropathic pain. Moreover, the IL-1beta expressed in astrocytes plays a significant role in modulating this pathway. PERSPECTIVE: This study showed that the glial-neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats. These results suggest that the glial-neuronal GRK2 pathway is a potentially important new target for the treatment of neuropathic pain. PMID- 24216331 TI - Can we predict pneumococcal bacteremia in patients with severe community-acquired pneumonia? AB - PURPOSE: This study aimed to evaluate the role of biomarkers as markers of pneumococcal bacteremia in severe community-acquired pneumonia (SCAP). MATERIALS AND METHODS: A prospective, single-center, observational cohort study of 108 patients with SCAP admitted to the intensive care department of a university hospital in Portugal was conducted. Leucocytes, C-reactive protein (CRP), lactate, procalcitonin (PCT), d-dimer, brain natriuretic peptide (BNP), and cortisol were measured within 12 hours after the first antibiotic dose. RESULTS: Fifteen patients (14%) had bacteremic pneumococcal pneumonia (BPP). They had significantly higher levels of median CRP (301 [interquartile range, or IQR], 230 350] mg/L vs 201 [IQR, 103-299] mg/L; P = .023), PCT (40 [IQR, 25-102] ng/mL vs 8 [IQR, 2-26] ng/mL; P < .001), BNP (568 [IQR, 478-2841] pg/mL vs 407 [IQR, 175 989] pg/mL; P = .027), and lactate (5.5 [IQR, 4.5-9.8] mmol/L vs 3.1 [IQR, 1.9 6.2] mmol/L; P = .009) than did patients without BPP. The discriminatory power evaluated by the area under the receiver operating characteristic curve (aROC) for PCT (aROC, 0.79) was superior to lactate (aROC, 0.71), BNP (aROC, 0.67), and CRP (aROC, 0.70). At a cutoff point of 17 ng/mL, PCT showed a sensitivity of 87%, a specificity of 67%, a positive predictive value of 30% and a negative predictive value of 97%, as a marker of pneumococcal bacteremia. CONCLUSIONS: In this cohort, significantly higher PCT, BNP, lactate, and CRP levels were found in BPP, and PCT presented the best ability to identify pneumococcal bacteremia. A PCT serum level lower than 17 ng/mL could identify patients with SCAP unlikely to have pneumococcal bacteremia. PMID- 24216332 TI - Complement C3 depletion links to the expansion of regulatory T cells and compromises T-cell immunity in human abdominal sepsis: a prospective pilot study. AB - PURPOSE: Complement depletion commonly occurred in septic patients, but this problem was often underestimated during the treatment process. This study was designed to determine the association between complement depletion and T-cell immunosuppression. METHODS: From November 2011 to March 2012, patients with severe abdominal sepsis were prospectively enrolled in a single center. The baseline levels of complement C3 were used to stratify subjects into 2 groups. Plasma levels of complement components, percentage of regulatory T cells (Tregs), and T-cell immunity indexes were monitored at times after admission. The relationship between C3 depletion and T-cell response was investigated, with clinical outcomes explored meanwhile. RESULTS: A total of 60 patients aged 43.9 +/- 11.3 years were included within the period. C3 depletion, occurring in 65% of enrolled subjects, was strongly correlated with Treg expansion (P = .001) and decreased CD4(+)/CD8(+) ratio (P = .008). This depletion was also related to prolonged hospital stay (P = .001), delayed time to operation (P < .001), increased postoperative complications (P = .036), and hospital expenditure (P < .001). CONCLUSIONS: Complement C3 depletion was found to be linked to the expansion of Tregs during abdominal sepsis. Such depletion and associated immunosuppression should be paid close attention in the critical care. PMID- 24216333 TI - Bedside rule secondary response in metabolic acid-base disorders is unreliable. PMID- 24216334 TI - More nutritional research needed to prevent and treat Acinetobacter infections. PMID- 24216336 TI - Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock. AB - PURPOSE: Central venous oxygen saturation (Scvo2) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo2 and central venous-to-arterial partial pressure of carbon dioxide difference (?Pco2) may provide additional information about survival. MATERIALS AND METHODS: We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo2 >= 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo2 (<70% or >= 70%) and ?Pco2 (<6 mm Hg or >= 6 mm Hg). RESULTS: Overall, 28-day mortality was 35.5%. For patients in whom the Scvo2 target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo2 exceeded 70% (P = .009). In patients with Scvo2 >= 70%, mortality was lower if ?Pco2 was <6 mm Hg than if ?Pco2 was >= 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 +/- 0.61 vs 0.21 +/- 0.31, respectively; P = .016). CONCLUSIONS: The combination of Scvo2 and ?Pco2 appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo2 alone. Patients who meet both targets appear to clear lactate more efficiently. PMID- 24216338 TI - The intersection of intimate partner violence and HIV in U.S. women: a review. AB - The purposes of this study were to (a) review original research in the United States on the intersection of HIV risk and intimate partner violence (IPV) in women, and (b) identify trends that promote nursing and public health prevention and intervention strategies. Twenty-three original, peer-reviewed articles in the medical literature from 2008 to April 2012 were reviewed. Articles were eligible for inclusion if they addressed both HIV and IPV in women. Studies identified relationships between intimate partner victimization and HIV risk behaviors. Other factors compounding the complex relationship between IPV and increased HIV risk in women included sexual decision-making, male behavior, and substance use. A promising trend was found in the publication of studies addressing interventions. Prospective studies are needed to determine causality and temporal associations. Nursing interventions should focus on identifying women at risk for IPV, assessing HIV exposure risks, and providing culturally sensitive interventions and preventive measures. PMID- 24216339 TI - Robust spike classification based on frequency domain neural waveform features. AB - OBJECTIVE: We introduce a new spike classification algorithm based on frequency domain features of the spike snippets. The goal for the algorithm is to provide high classification accuracy, low false misclassification, ease of implementation, robustness to signal degradation, and objectivity in classification outcomes. APPROACH: In this paper, we propose a spike classification algorithm based on frequency domain features (CFDF). It makes use of frequency domain contents of the recorded neural waveforms for spike classification. The self-organizing map (SOM) is used as a tool to determine the cluster number intuitively and directly by viewing the SOM output map. After that, spike classification can be easily performed using clustering algorithms such as the k-Means. MAIN RESULTS: In conjunction with our previously developed multiscale correlation of wavelet coefficient (MCWC) spike detection algorithm, we show that the MCWC and CFDF detection and classification system is robust when tested on several sets of artificial and real neural waveforms. The CFDF is comparable to or outperforms some popular automatic spike classification algorithms with artificial and real neural data. SIGNIFICANCE: The detection and classification of neural action potentials or neural spikes is an important step in single-unit-based neuroscientific studies and applications. After the detection of neural snippets potentially containing neural spikes, a robust classification algorithm is applied for the analysis of the snippets to (1) extract similar waveforms into one class for them to be considered coming from one unit, and to (2) remove noise snippets if they do not contain any features of an action potential. Usually, a snippet is a small 2 or 3 ms segment of the recorded waveform, and differences in neural action potentials can be subtle from one unit to another. Therefore, a robust, high performance classification system like the CFDF is necessary. In addition, the proposed algorithm does not require any assumptions on statistical properties of the noise and proves to be robust under noise contamination. PMID- 24216337 TI - A role for orexin in cytotoxic chemotherapy-induced fatigue. AB - Fatigue is the most common symptom related to cytotoxic chemotherapeutic treatment of cancer. Peripheral inflammation associated with cytotoxic chemotherapy is likely a causal factor of fatigue. The neural mechanisms by which cytotoxic chemotherapy associated inflammation induces fatigue behavior are not known. This lack of knowledge hinders development of interventions to reduce or prevent this disabling symptom. Infection induced fatigue/lethargy in rodents is mediated by suppression of hypothalamic orexin activity. Orexin is critical for maintaining wakefulness and motivated behavior. Though there are differences between infection and cytotoxic chemotherapy in some symptoms, both induce peripheral inflammation and fatigue. Based on these similarities we hypothesized that cytotoxic chemotherapy induces fatigue by disrupting orexin neuron activity. We found that a single dose of a cytotoxic chemotherapy cocktail (cyclophosphamide, adriamycin, 5-fluorouracil - CAF) induced fatigue/lethargy in mice and rats as evidenced by a significant decline in voluntary locomotor activity measured by telemetry. CAF induced inflammatory gene expression - IL-1R1 (p<0.001), IL-6 (p<0.01), TNFalpha (p<0.01), and MCP-1 (p<0.05) - in the rodent hypothalamus 6-24h after treatment during maximum fatigue/lethargy. CAF decreased orexin neuron activity as reflected by decreased nuclear cFos localization in orexin neurons 24h after treatment (p<0.05) and by decreased orexin-A in cerebrospinal fluid 16 h after treatment (p<0.001). Most importantly, we found that central administration of 1 MUg orexin-A restored activity in CAF-treated rats (p<0.05). These results demonstrate that cytotoxic chemotherapy induces hypothalamic inflammation and that suppression of hypothalamic orexin neuron activity has a causal role in cytotoxic chemotherapy-induced fatigue in rodents. PMID- 24216340 TI - Kinetic model of Chlorella vulgaris growth with and without extremely low frequency-electromagnetic fields (EM-ELF). AB - Chlorella vulgaris was grown in two bench-scale photobioreactors with and without the application of a low intensity, low frequency electromagnetic field (EM-ELF) of about 3mT. Cell concentration and tendency of cells to form aggregates inside the reactor were recorded over a 30 days-time period at 0.5L-constant medium volume in the temperature range 289-304K. At 304K, after a cultivation period of 15 days, the rate of cell death became predominant over that of growth. In the temperature range 289-299K, a two step-kinetic model based on the mitotic division and the clusterization processes was developed and critically discussed. The best-fitted curves turned out to have a sigmoid shape, and the competition between mitosis and clusterization was investigated. Without EM-ELF, the temperature dependence of the specific rate constant of the mitotic step yielded an apparent total enthalpy of 15+/-6kJmol(-1), whose value was not influenced by the EM-ELF application. The electromagnetic field was shown to exert a significant effect on the exothermic clusterization step. The heat exchange due to binding between cells and liquid medium turned out to be -44+/-5kJmol(-1) in the absence of EM-ELF and -68+/-8kJmol(-1) when it was active. Optical microscopy observations were in agreement with the model predictions and confirmed that EM ELF was able to enhance cell clusterization. PMID- 24216341 TI - Tools for advanced and targeted genetic manipulation of the beta-lactam antibiotic producer Acremonium chrysogenum. AB - Acremonium chrysogenum is the major producer of the beta-lactam antibiotic cephalosporin C and therefore of great importance for the pharmaceutical industry. However, this filamentous fungus is known to reproduce solely by asexual means, shows only sporadic conidiospore production, and has gradual fragmentation of the vegetative mycelium into arthrospores. Due to these peculiar growth characteristics and life style, strain improvement by recombinant technologies is much more challenging than for other biotechnologically relevant fungi. Here, we describe several molecular tools for genetic engineering of A. chrysogenum, including a DeltaAcku70 deletion strain for homologous recombination. No physiological or morphological changes occurred due to deletion of the ku70 gene or integration of the nat1 cassette in this recipient strain. We also used a xylose-inducible promoter from Sordaria macrospora (Smxyl) to demonstrate induction of the gfp reporter gene in A. chrysogenum. The Smxyl promoter was used for construction of a vector molecule to develop a one-step FLP/FRT recombination system in A. chrysogenum. This system was then used in the DeltaAcku70 deletion strain to construct a marker-free recipient strain for targeted DNA insertion into genomic DNA. The applicability of our tools was demonstrated by construction of a marker-free transgenic strain, lacking any foreign genes. PMID- 24216342 TI - Effect of immediate and continuous mother-infant skin-to-skin contact on breastfeeding self-efficacy of primiparous women: a randomised control trial. AB - OBJECTIVE: To evaluate the effect of mother-infant immediate skin-to-skin contact on primiparous mother's breastfeeding self-efficacy. STUDY DESIGN: A randomised control trial. SETTINGS: The study was conducted in Omolbanin obstetrics hospital (large tertiary hospital), Mashhad, Iran. PARTICIPANTS: 114 18-35 year-old primiparous, Iranian, healthy and full term mothers who anticipated normal vaginal delivery and intended to breastfeed their babies. INTERVENTION: Skin-to skin contact immediately after birth and then controlling breastfeeding self efficacy at 28 days postpartum. MAIN OUTCOME MEASURE: Maternal breastfeeding self efficacy at 28 days postpartum and success in first breastfeeding and mean time of first breastfeeding initiation. RESULTS: A total of 92 mother-infant dyads (47 dyads in skin-to-skin care skin-to-skin contact group and 45 dyads in routine care group) were monitored and analysed. In skin-to-skin contact group, breastfeeding self-efficacy was 53.42+/-8.57 SD as compared to 49.85+/-5.50 SD in routine care group which is significantly higher in skin-to-skin contact group (p=0.0003). Successful breastfeeding initiation rate was 56.6% in skin-to-skin contact group as compared to 35.6% in routine care group (p=0.02). Time to initiate first feed was 21.98+/-9.10 SD min in SSC group vs. 66.55+/-20.76 min in routine care group (p<0.001). CONCLUSION: Mother-infant immediate skin-to-skin contact is an easy and available method of enhancing maternal breastfeeding self efficacy. High breastfeeding self-efficacy increases exclusive breastfeeding duration. PMID- 24216343 TI - Physical activity practice, body image and visual impairment: a comparison between Brazilian and Italian children and adolescents. AB - The aim of this study was to analyze the physical activity and body image of children and adolescents with visual impairment (VI) in Brazil and Italy. For this, 41 children and adolescents with VI (19 Brazilian and 22 Italian) aged 10.22 +/- 2.19 years old (18 girls and 23 boys) answered the Physical Activity Questionnaire for Children (PAQ-C), the Offer Self-Image Questionnaire (OSIQ), and an instrument with information about the disability, body weight and height. We analyzed the relationship between data from PAQ-C and OSIQ, as well as the gender, level of disability (blindness or low vision) and country using independent Mann-Whitney test. Body mass index (BMI) values were higher for Brazilian youths, with more than half of them classified as overweight and obese. Italian youths exhibited values of body image that were more positive and only 27% presented overweight or obesity. Blind children and adolescents were less active than those with low vision, but no differences were found between countries or genders. In Brazil, we detected significant correlations (p>0.05) between physical activity, body image and BMI, which more active youths presenting lower values of BMI and a better perception of body image. Physical activity seems to have a positive influence on body image and BMI for children and adolescents with VI, thus it should be encouraged especially for those with higher disability degrees. PMID- 24216344 TI - Enumeration of small and large numerosities in adolescents with mathematical learning disorders. AB - The accuracy and speed in an enumeration task were investigated in adolescents with typical and atypically poor development of arithmetic skills. The number naming performances on small and large non-symbolic numerosities of 18 adolescents with mathematical learning disorders (MLD) and 28 typically achieving age-matched (TA) adolescents were compared. A mixed logistic regression model showed that adolescents with MLD were not significantly less accurate on numbers within the subitizing range than control peers. Moreover, no significant differences in reaction times were found between both groups. Nevertheless, we found that within the control group adolescents with higher ability tended to respond faster when taking into account the whole range (1-9) of numerosities. This correlation was much weaker in the MLD group. When looking more closely at the data, however, it became clear that the correlation between accuracy and speed within the control group differed in direction dependent on the range (subitizing or counting) of the numerosities. As such, our findings did not support a limited capacity of subitizing in MLD. However, the data stressed a different correlation between speed and accuracy for both groups of adolescents and a different behavioral pattern depending on the numerosity range as well. Implications for the understanding and approach of MLD are considered. PMID- 24216345 TI - Correlates of self-injurious, aggressive and destructive behaviour in children under five who are at risk of developmental delay. AB - AIM: Several behavioural correlates of self-injury, aggression and destructive behaviour have been identified in children and young adults with intellectual disabilities. This cross-sectional study aimed to further explore these correlates in very young children with developmental delay. METHODS: Parents of 56 children (40 male) under the age of five years (mean age 2 years 10 months) completed a questionnaire about their child's behaviour and the presence of behavioural correlates, including repetitive, over-active or impulsive behaviour and more severe developmental delay. RESULTS: Parents reported very high prevalence of self-injurious, aggressive and destructive behaviour: 51%, 64% and 51%, respectively. A binary logistic regression revealed that a higher score on a measure of overactive and impulsive behaviour significantly predicted the presence of destructive behaviour. A multiple linear regression revealed that both repetitive behaviour and number of health problems approached significance as independent predictors of severe self-injurious behaviour. INTERPRETATION: Despite the very small sample, several factors emerged as potential predictors of self-injurious, aggressive and destructive behaviour. These findings support the need for further investigation in a larger sample. Confirmation in this age group could help guide the development of targeted early intervention for these behaviours by identifying behavioural risk markers. PMID- 24216346 TI - Advances and challenges for nutrient management in china in the 21st century. AB - Managing agricultural nutrients to provide a safe and secure food supply while protecting the environment remains one of the great challenges for the 21st century. The fourth International Nutrient Management Symposium (INMS), held in 2011 at the University of Delaware, addressed these issues via presentations, panel sessions, and field tours focused on latest technologies and policies available to increase nutrient use efficiency. Participants from the United States, Europe, Canada, and China discussed global trends and challenges, balancing food security and the environment in countries with struggling and emerging economics, nutrient management and transport at the catchment scale, new technologies for managing fertilizer and manure nutrients, and adaptive nutrient management practices for farm to watershed scales. A particular area of interest at the fourth INMS was nutrient management progress and challenges in China over the past 40 years. China's food security challenges and rapidly growing economy have led to major advances in agricultural production systems but also created severe nutrient pollution problems. This special collection of papers from the fourth INMS gives an overview of the remarkable progress China has made in nutrient management and highlights major challenges and changes in agri environmental policies and practices needed today. Lessons learned in China are of value to both developing and developed countries facing the common task of providing adequate food for an expanding world population, while protecting air and water quality and restoring damaged ecosystems. PMID- 24216347 TI - An analysis of developments and challenges in nutrient management in china. AB - During the past 50 years, China has successfully realized food self-sufficiency for its rapidly growing population. Currently, it feeds 22% of the global population with 9% of the global area of arable land. However, these achievements were made at high external resource use and environmental costs. The challenge facing China is to further increase food production while drastically decreasing the environmental costs of food production. Here we review the major developments in nutrient management in China over the last 50 years. We briefly analyze the current organizational structure of the "advisory system" in agriculture, the developments in nutrient management for crop production, and the developments in nutrient management in animal production. We then discuss the nutrient management challenges for the next decades, considering nutrient management in the whole chain of crop production-animal production-food processing-food consumption by households. We argue that more coherent national policies and institutional structures are required for research extension education to be able to address the immense challenges ahead. Key actions include nutrient management in the whole food chain concomitant with a shift in objectives from food security only to food security, resource use efficiency, and environmental sustainability; improved animal waste management based on coupled animal production and crop production systems; and much greater emphasis on technology transfer from science to practice through education, training, demonstration, and extension services. PMID- 24216348 TI - The driving forces for nitrogen and phosphorus flows in the food chain of china, 1980 to 2010. AB - Nitrogen (N) and phosphorus (P) use and losses in China's food chain have accelerated in the past three decades, driven by population growth, rapid urbanization, dietary transition, and changing nutrient management practice. There has been little detailed quantitative analysis of the relative magnitude of these driving forces throughout this period. Therefore, we analyzed changes in N and P flows and key drivers behind changes in the food (production and consumption) chain at the national scale from 1980 to 2010. Food (N and P) consumption increased by about fivefold in urban settings over this period but has decreased in rural settings since the 1990s. For urban settings, the integrated driving forces for increased food consumption were population growth, which accounted for ~60%, and changing urban diets toward a greater emphasis on the consumption of animal products. Nutrient inputs and losses in crop and animal productions have continuously increased from 1980 to 2010, but the rates of decadal increase were greatly different. Increased total inputs and losses in crop production were primarily driven by increased crop production for food demand (68-96%) in the 1980s but were likely offset in the 2000s by improved nutrient management practices, as evidenced by decreased total inputs to and losses from cropland for harvesting per nutrient in crop. The contributions of animal production to total N and P losses to waters from the food chain increased by 34 and 60% from 1980 to 2010. These increases were caused mainly by decreased ratios of manure returned to cropland. Our study highlights a larger impact of changing nutrient management practice than population growth on elevated nutrient flows in China's food chain. PMID- 24216349 TI - An Analysis of China's Fertilizer Policies: Impacts on the Industry, Food Security, and the Environment. AB - China has made remarkable strides in recent decades to grow enough food to feed 20% of the world's population with only 9% of the world's arable land. Meanwhile, the nation is experiencing exacerbated air and water pollution problems. Agricultural growth and the pollution aggravation are closely linked with policies affecting fertilizer production and use. Essentially nonexistent in 1950, China's fertilizer industry is now a robust conglomerate producing fertilizers in amounts that not only meet domestic demand but also contribute to international trade. The industry's growth stemmed from a series of policy progressions, featuring (i) a total control system with state ownership and central planning (1949-1984), (ii) a dual system of central planning and market adjustment (1985-1997), (iii) a market-driven system with government-mandated price caps (1998-2009), and (iv) a complete market-oriented system (since 2009). In conjunction with the policy changes were massive subsidy programs totaling more than $18 billion in 2010. The support policies and subsidies helped grow the industry and safeguard an adequate supply of fertilizers at affordable costs to farmers, but the artificially low-priced fertilizers also contributed to a nationwide trend of fertilizer overuse, leading to nutrient pollution. China needs innovative policies and programs to address food security and sustainability challenges. In this study, we review and analyze policies and programs related to China's fertilizer production and use in a 60-yr span (1950 2010) and discuss its impact on the development of the industry, food security, and pressing environmental issues. Finally, our study analyzes long-term trends in fertilizer use in China and offers some key viewpoints to stimulate debates among all stakeholders. PMID- 24216350 TI - Phosphorus in China's Intensive Vegetable Production Systems: Overfertilization, Soil Enrichment, and Environmental Implications. AB - China's vegetable production has experienced a rapid growth in recent years. Total production amounted to 522.7 million Mg (1 Mg = 10 g) in 2009, which was more than nine times that in 1980 and represented >50% of the world production. Meanwhile, excessive use of animal manures and chemical fertilizers in vegetable fields has brought various production and environmental challenges, including excessive accumulation of nutrients in soils and accelerated water pollution problems. In this study, we have evaluated the current status of phosphorus (P) in China's intensive vegetable production systems based on data summarized from nearly 100 publications plus results from our recent experiments. Gross overfertilization occurred in greenhouse (571 kg P ha) and open-field (117 kg P ha) vegetable systems compared with P removal in harvested crops (44 and 25 kg P ha) per season. Excess P input led to soil enrichment of labile P, measured as Olsen-P, averaging 179 (greenhouses) and 100 mg P kg (open fields) in the 0- to 20-cm soil depth, and in some cases led to P leaching, as evidenced by increases in Olsen-P and CaCl-P at the 40- to 60-cm soil depth. The vast majority of vegetable soils had Olsen-P exceeding the critical level (46.0-58.0 mg P kg) for optimum vegetable yield. Innovative policies and strategies are urgently needed to implement science-based nutrient management practices to attain sustainable vegetable production while protecting natural and environmental resources. PMID- 24216351 TI - Nitrogen and phosphorus use efficiencies in dairy production in china. AB - Milk production has greatly increased in China recently, with significant impacts on the cycling of nitrogen (N) and phosphorus (P). However, nutrient flows within the changing dairy production system are not well quantified. The aim of this study was to increase the quantitative understanding of N and P cycling and utilization in dairy production through database development and simulation modeling. In 2010, of the entire 1987 and 346 thousand tons (Gg) of N and P input, only 188 Gg N and 31 Gg P ended up in milk. The average N and P use efficiencies were 24 and 25%, respectively, at the whole system level. Efficiencies differed significantly between the four dairy systems. Losses of N from these systems occurred via NH volatilization (33%), discharge (27%), denitrification (24%), NO leaching and runoff (16%), and NO emission (1%). Industrial feedlots use less feed per kg milk produced than traditional systems, and rely more on high-quality feed from fertilized cropland; they have very poor recycling of manure nutrients to cropland. As industrial feedlot systems are booming, overall mean N and P use efficiencies will increase at herd level but will decrease at the whole dairy production system level unless manure N and P are used more efficiently through reconnecting China's feed and dairy production sectors. PMID- 24216352 TI - A review of stream nutrient criteria development in the United States. AB - Elevated nutrients and sediments are the main factors contributing to the poor biological condition measured in over 40% of US waters, highlighting the need for criteria that can aid management efforts to protect or restore the quality of US waters. A large amount of literature on nutrient criteria has been generated since the USEPA called for their development in 1998. Our objective was to examine this peer-reviewed literature to evaluate two main approaches for criteria development in lotic ecosystems: percentile rank and bivariate predictive statistical analyses. The 25th percentile approach has been examined broadly across USEPA-aggregate nutrient ecoregions, and we found that USEPA suggested criteria for these aggregate ecoregions were often more conservative than criteria estimated using more current regionally focused data based on our compiled data set. Furthermore, 25th percentile estimates were often less than 75th percentile estimates based on reference sites, suggesting that 75th percentile estimates were not more conservative than 25th percentile estimates. Predictive approaches have focused on establishing linear and nonlinear relationships between water quality and algae, macroinvertebrate, and fish communities; attributing causation; and determining whether threshold points exist that can aid in nutrient criteria development. Most of the predictive approaches have occurred at the state or watershed level and may not be directly comparable to USEPA aggregate ecoregions. However, percentile method estimates often fell within the confidence interval of biological threshold criteria estimates, suggesting overlap and some consensus between the two main approaches. PMID- 24216353 TI - Review of the application of near-infrared spectroscopy technology to determine the chemical composition of animal manure. AB - Animal manure contains a variety of chemical constituents that are highly valuable to agriculture, including nitrogen, phosphorus, potassium, and metal micronutrients. Although appropriately applied manure has numerous positive attributes, the excessive application of manure may lead to pollution of the atmosphere, water, or soil. To reconcile precision agriculture and the potential negative environmental influences of animal manure, it is necessary to develop rapid and robust methods to evaluate the chemical composition of animal manure. This paper summarizes recent advances in near-infrared reflectance spectroscopy (NIRS) in predicting moisture, dry matter, organic matter, nitrogen, phosphorus, carbon, and metal content in animal manure. The results indicate the high potential of NIRS as an efficient tool for monitoring the chemical composition of animal manure. Future prospects and needs related to increasing the feasibility of the industrial application of NIRS and improving NIRS prediction precision in determining the chemical composition of animal manure are discussed. PMID- 24216354 TI - Particulate emissions calculations from fall tillage operations using point and remote sensors. AB - Soil preparation for agricultural crops produces aerosols that may significantly contribute to seasonal atmospheric particulate matter (PM). Efforts to reduce PM emissions from tillage through a variety of conservation management practices (CMPs) have been made, but the reductions from many of these practices have not been measured in the field. A study was conducted in California's San Joaquin Valley to quantify emissions reductions from fall tillage CMP. Emissions were measured from conventional tillage methods and from a "combined operations" CMP, which combines several implements to reduce tractor passes. Measurements were made of soil moisture, bulk density, meteorological profiles, filter-based total suspended PM (TSP), concentrations of PM with an equivalent aerodynamic diameter <=10 MUm (PM) and PM with an equivalent aerodynamic diameter <=2.5 MUm (PM), and aerosol size distribution. A mass-calibrated, scanning, three-wavelength light detection and ranging (LIDAR) procedure estimated PM through a series of algorithms. Emissions were calculated via inverse modeling with mass concentration measurements and applying a mass balance to LIDAR data. Inverse modeling emission estimates were higher, often with statistically significant differences. Derived PM emissions for conventional operations generally agree with literature values. Sampling irregularities with a few filter-based samples prevented calculation of a complete set of emissions through inverse modeling; however, the LIDAR-based emissions dataset was complete. The CMP control effectiveness was calculated based on LIDAR-derived emissions to be 29 +/- 2%, 60 +/- 1%, and 25 +/- 1% for PM, PM, and TSP size fractions, respectively. Implementation of this CMP provides an effective method for the reduction of PM emissions. PMID- 24216355 TI - A new approach to developing a fugitive road dust emission inventory and emission trend from 2006 to 2010 in the beijing metropolitan area, china. AB - The USEPA emission factor (AP-42) of fugitive road dust (FRD) is widely used in establishing emission inventories. However, road silt loading sampling for AP-42 is expensive, time consuming, and dangerous. Therefore, a new method for establishing emission inventories based on road dust-fall (DF) monitors is described. Between January 2006 and December 2010, DF was monitored at 40 sites (80 samples), and background dust fall (DF) was monitored at 14 sites in the Beijing metropolitan area. Also during this period, 58 samples of road silt loadings were taken and used in the AP-42 emission factor equation to calculate FRD with particulate matter <=10 MUm in diameter [FRD(PM)] emission from the roads. Simultaneous measurement of FRD(PM) emissions calculated by AP-42 and DeltaDF (i.e., the difference between the DF and DF) measured using gauges showed that the FRD(PM) emission for road dust was proportional to the DeltaDF ( = 0.92). The FRD(PM) emission (kg km * 30 d) was calculated using the monitored DeltaDF (t km * 30 d) by the formulation FRD(PM) = 278.3 * DeltaDF - 1151.2. The DeltaDF showed a general decline from 2006 to 2010. In particular, there was a sharp decline in August, September, and October 2008 due to strict dust controls enforced during the 2008 Olympic Games. Although there was a small increase in DeltaDF after the Games, by the end of 2010 values were still lower than those before the Games. Using the 2006 DeltaDF value as a benchmark, DeltaDF values declined by 24.7, 33.0, 38.3, and 31.4% in 2007, 2008, 2009, and 2010, respectively. Based on using AP-42 calculations from silt loading and traffic information in 2007, the FRD(PM) emission distribution in the Beijing metropolitan area was mapped, and there were 2.05 * 10 tons of FRD(PM) emitted in 2007. The FRD(PM) from 2006 to 2010 was calculated by the DeltaDF values. PMID- 24216356 TI - Nitrous oxide production from soils amended with biogas residues and cattle slurry. AB - The amount of residues generated from biogas production has increased dramatically due to the worldwide interest in renewable energy. A common way to handle the residues is to use them as fertilizers in crop production. Application of biogas residues to agricultural soils may be accompanied with environmental risks, such as increased NO emission. In 24-d laboratory experiments, NO dynamics and total production were studied in arable soils (sandy, clay, and organic) amended with one of two types of anaerobically digested biogas residues (BR-A and BR-B) generated from urban and agricultural waste and nondigested cattle slurry (CS) applied at rates corresponding to 70 kg NH-N ha. Total NO-N losses from the sandy soil were higher after amendment with BR-B (0.32 g NO-N m) than BR-A or CS (0.02 and 0.18 g NO-N m, respectively). In the clay soil, NO-N losses were very low for CS (0.02 g NO-N m) but higher for BR-A and BR-B (0.25 and 0.15 g NO-N m, respectively). In the organic soil, CS gave higher total NO-N losses (0.31 g NO-N m) than BR-A or BR-B (0.09 and 0.08 g NO-N m, respectively). Emission peaks differed considerably between soils, occurring on Day 1 in the organic soil and on Days 11 to 15 in the sand, whereas in the clay the peak varied markedly (Days 1, 6, and 13) depending on residue type. In all treatments, NH concentration decreased with time, and NO concentration increased. Potential ammonium oxidation and potential denitrification activity increased significantly in the amended sandy soil but not in the organic soil and only in the clay amended with CS. The results showed that fertilization with BR can increase NO emissions and that the size is dependent on the total N and organic C content of the slurry and on soil type. In conclusion, the two types of BR and the CS are not interchangeable regarding their effects on NO production in different soils, and, hence, matching fertilizer type to soil type could reduce NO emissions. For instance, it could be advisable to avoid fertilization of organic soils with CS containing high amounts or organic C and instead use BR. In clay soil, however, the risk of NO emissions could be lowered by choosing a CS. PMID- 24216357 TI - Methane emissions from drill-seeded, delayed-flood rice production on a silt-loam soil in arkansas. AB - Rice ( L.) production is unique among staple food crops because the majority of the growing season typically occurs under flooded-soil conditions. Flooding the soil leads to anaerobic conditions, which are a precursor to methane (CH) production. However, no known research has investigated CH emissions from the drill-seeded, delayed-flood rice production system common in Arkansas, the leading rice-producing state in the United States. Therefore, research was conducted in 2011 to determine the effects of vegetation (rice and bare soil), chamber location (in- and between-rice rows), and nitrogen (N) fertilization (optimal and no N) on CH emissions from a silt-loam soil. Methane fluxes measured weekly from flooding until flood release were affected by vegetation, chamber location, and sample date ( < 0.05). In-row CH fluxes were <0.7 mg CH-C m h until 20 d after flooding (DAF) and <1.0 mg CH-C m h from between-row and bare soil until 41 DAF and were unaffected by fertilization over time. The largest weekly measured CH flux (31.9 mg CH-C m h) was observed from in-row rice at 41 DAF. Post flood-release CH fluxes were affected by vegetation, fertilization, chamber placement, and sample date ( < 0.05) and accounted for approximately 3 to 7% of the season-long CH emissions. Methane emissions averaged 195 kg CH-C ha per growing season and were unaffected by fertilization. Direct measurement of CH emissions from drill-seeded, delayed-flood rice grown on a silt-loam soil will improve the accuracy of assessments of the carbon footprint and long-term sustainability of rice. PMID- 24216358 TI - Wavelet analysis of the variability of nitrous oxide emissions from soil at decameter to kilometer scales. AB - We analyzed data on nitrous oxide emissions and on soil properties that were collected on a 7.5-km transect across an agricultural landscape in eastern England using the discrete wavelet packet transform. We identified a wavelet packet "best basis" for the emission data. Wavelet packet basis functions are used to decompose the data into a set of coefficients that represent the variation in the data at different spatial frequencies and locations. The "best basis" for a set of data is adapted to the variability in the data by ensuring that the spatial resolution of local features is good at those spatial frequencies where variation is particularly intermittent. The best basis was shown to be adapted to represent such intermittent variation, most markedly at wavelengths of 100 m or less. Variation at these wavelengths was shown to be correlated particularly with chemical properties of the soil, such as nitrate content. Variation at larger wavelengths showed less evidence of intermittency and was found to be correlated with soil chemical and physical constraints on emission rates. In addition to frequency-dependent intermittent variation, it was found that the variance of emission rates at some wavelengths changed at particular locations along the transect. One factor causing this appeared to be contrasts in parent material. The complex variation in emission rates identified by these analyses has implications for how emission rates are estimated. PMID- 24216359 TI - Short-term biodegradation of petroleum in planted and unplanted sandy soil. AB - A greenhouse experiment was conducted to determine the effect of microbial populations and biodegradation of petroleum hydrocarbons in Lam. 'Passerel Plus' planted and unplanted contaminated sandy soil. Plant adaptation, growth, photosynthesis, rhizosphere microbial population, and total petroleum hydrocarbon (TPH) degradation were determined. Petroleum contamination resulted in reduced plant growth, photosynthesis, and macro- and micronutrient content. Filamentous fungi populations were stimulated by the petroleum concentrations, especially when plants were exposed to intermediate to high petroleum contamination. In general, unplanted containers had lower bacterial colony forming units compared with planted containers. Thus, bacterial populations were stimulated by the rhizosphere effect of when compared with fungal populations. Degradation of TPH was greater in the lower petroleum concentration when compared with the higher petroleum concentrations in the soil and was not affected by plant presence. Nevertheless, the TPH biodegradation occurred at greater rates: 48 mg kg d for concentration of 3000 mg kg and 66 and 165 mg kg d for concentrations of 6000 and 15,000 mg kg, respectively, which concurs with the high fungal and bacterial populations with increasing petroleum concentrations regardless of plant presence. PMID- 24216360 TI - System dynamics modeling of nitrogen removal in a stormwater infiltration basin with biosorption-activated media. AB - Stormwater infiltration basins, one of the typical stormwater best management practices, are commonly constructed for surface water pollution control, flood mitigation, and groundwater restoration in rural or residential areas. These basins have soils with better infiltration capacity than the native soil; however, the ever-increasing contribution of nutrients to groundwater from stormwater due to urban expansion makes existing infiltration basins unable to meet groundwater quality criteria related to environmental sustainability and public health. This issue requires retrofitting current infiltration basins for flood control as well as nutrient control before the stormwater enters the groundwater. An existing stormwater infiltration basin in north-central Florida was selected, retrofitted, and monitored to identify subsurface physiochemical and biological processes during 2007-2010 to investigate nutrient control processes. This implementation in the nexus of contaminant hydrology and ecological engineering adopted amended soil layers packed with biosorption activated media (BAM; tire crumb, silt, clay, and sand) to perform nutrient removal in a partitioned forebay using a berm. This study presents an infiltration basin-nitrogen removal (IBNR) model, a system dynamics model that simulates nitrogen cycling in this BAM-based stormwater infiltration basin with respect to changing hydrologic conditions and varying dissolved nitrogen concentrations. Modeling outputs of IBNR indicate that denitrification is the biogeochemical indicator in the BAM layer that accounted for a loss of about one third of the total dissolved nitrogen mass input. PMID- 24216361 TI - Simulation of Nitrous Oxide Emissions and Estimation of Global Warming Potential in Turfgrass Systems Using the DAYCENT Model. AB - Nitrous oxide (NO) emissions are an important component of the greenhouse gas budget for turfgrasses. To estimate NO emissions and global warming potential, the DAYCENT ecosystem model was parameterized and applied to turfgrass ecosystems. The annual cumulative NO emissions predicted by the DAYCENT model were close to the measured emission rates of Kentucky bluegrass ( L.) sites in Colorado (within 16% of the observed values). For the perennial ryegrass ( L.) site in Kansas, the DAYCENT model initially overestimated the NO emissions for all treatments (urea and ammonium sulfate at 250 kg N ha yr and urea at 50 kg N ha yr) by about 200%. After including the effect of biological nitrification inhibition in the root exudate of perennial ryegrass, the DAYCENT model correctly simulated the NO emissions for all treatments (within 8% of the observed values). After calibration and validation, the DAYCENT model was used to simulate NO emissions and carbon sequestration of a Kentucky bluegrass lawn under a series of management regimes. The model simulation suggested that gradually reducing fertilization as the lawn ages from 0 to 50 yr would significantly reduce long term NO emissions by approximately 40% when compared with applying N at a constant rate of 150 kg N ha yr. Our simulation indicates that a Kentucky bluegrass lawn in Colorado could change from a sink to a weak source of greenhouse gas emissions 20 to 30 yr after establishment. PMID- 24216362 TI - Sensitivity and uncertainty analysis for the annual phosphorus loss estimator model. AB - Models are often used to predict phosphorus (P) loss from agricultural fields. Although it is commonly recognized that model predictions are inherently uncertain, few studies have addressed prediction uncertainties using P loss models. In this study we assessed the effect of model input error on predictions of annual P loss by the Annual P Loss Estimator (APLE) model. Our objectives were (i) to conduct a sensitivity analyses for all APLE input variables to determine which variables the model is most sensitive to, (ii) to determine whether the relatively easy-to-implement first-order approximation (FOA) method provides accurate estimates of model prediction uncertainties by comparing results with the more accurate Monte Carlo simulation (MCS) method, and (iii) to evaluate the performance of the APLE model against measured P loss data when uncertainties in model predictions and measured data are included. Our results showed that for low to moderate uncertainties in APLE input variables, the FOA method yields reasonable estimates of model prediction uncertainties, although for cases where manure solid content is between 14 and 17%, the FOA method may not be as accurate as the MCS method due to a discontinuity in the manure P loss component of APLE at a manure solid content of 15%. The estimated uncertainties in APLE predictions based on assumed errors in the input variables ranged from +/-2 to 64% of the predicted value. Results from this study highlight the importance of including reasonable estimates of model uncertainty when using models to predict P loss. PMID- 24216363 TI - Dependence of arsenic fate and transport on biogeochemical heterogeneity arising from the physical structure of soils and sediments. AB - Reduction of As(V) and Fe(III) is commonly the dominant process controlling the fate and transport of As in soils and sediments. However, the physical structure of such environments produces complex heterogeneity in biogeochemical processes controlling the fate and transport of As. To resolve the role of soil and sediment physical structure on the distribution of biogeochemical processes controlling the fate and transport of As, we examined the biogeochemical transformations of As and Fe within constructed aggregates-a fundamental unit of soil structure. Spherical aggregates were made with As(V)- or As(III)-bearing, ferrihydrite-coated quartz that was fused with agarose and placed in a cylindrical reactor; advective flow of anoxic solutes was then initiated around the aggregates to examine As release from a dual-pore domain system. To examine the impact of biotic As(V) and Fe(III) reduction, constructed aggregates having As(V)-bearing, ferrihydrite-coated quartz inoculated with sp. ANA-3 were placed in flow-through reactors under anoxic and aerated advective flow. Consistent with desorption from advective columns, As(III) is released to advecting water more prevalently than As(V) within abiotic aggregate systems, indicating a greater lability and concomitant enhanced propensity for transport of As(III) relative to As(V). During reaction with , As release to advecting water was similar between anoxic and aerated systems for the first 20 d; thereafter, the anoxic advecting solutes increased As release relative to the aerated counterpart. With aerated advecting solutes, Fe remained oxidized (or was oxidized) in the aggregate exterior, forming a protective barrier that limited As release to the advective channel. However, anaerobiosis within the aggregate interior, even with aerated advective flow, promotes internal repartitioning of As to the exterior region. PMID- 24216364 TI - Arsenic mobility and speciation in a gleysol with petrogleyic properties: a field and laboratory approach. AB - Naturally elevated levels of As have been observed in some iron-enriched lowland soils of the southern Munsterland, Germany. To determine whether As is mobilized by the reductive dissolution of As-hosting Fe oxides at reducing soil conditions, the release of arsenate and arsenite was investigated in the field for 24 mo and in laboratory experiments. The grassland Gleysol consists of oximorphic soil horizons (Ah 0-15, Bg 15-35, CrBg 35-70 cm) developed from fluvial loam overlaying sand with reductomorphic properties (2Cr, +70 cm). The soil has petrogleyic properties due to enrichment of oxidic Fe in the Bg and CrBg horizons (275 and 390 g kg, respectively). Most of the petrogleyic Fe belonged to nanosized goethite, whereas ferrihydrite was dominant in the topsoil. Arsenic levels of 149 mg kg were found in the topsoil. Levels peaked in the oximorphic soil horizons (626 and 999 mg kg, respectively) and were lowest in the sand (12 mg kg). Sequential fractionation revealed that 84 to 96% of the As in the oximorphic horizons was associated with Fe oxides. Water saturation in combination with soil temperatures above 5 to 10 degrees C resulted in a fast decrease of the redox potential (up to -120 mV) and release of As (up to 35 MUg L) with Fe into the soil solution only in the Ah horizon. Although the petrogleyic horizons were mostly water saturated with reducing conditions, no As release was observed. A lack of As mobilization was confirmed in experiments performed under fixed redox conditions; neither Fe nor As was released into solution at an appropriate redox potential. The As species distribution showed redox disequilibrium because arsenate was detected under reducing conditions and arsenite under oxidizing conditions. We conclude that microbial-mediated reductive dissolution of Fe oxides pushes the As mobilization in the topsoil; water saturation and soil temperature were key factors. The dominance of goethite, which is more resistant to microbial reduction, and/or the possible readsorption of released As onto remaining or newly formed Fe oxide surfaces is responsible for the absent As mobilization in the petrogleyic horizons. PMID- 24216365 TI - Subcellular accumulation of different concentrations of cadmium, nickel, and copper in Indian mustard and application of a sigmoidal model. AB - Certain plant species can tolerate and even detoxify metallic elements. This detoxification ability has been shown to depend on how plants distribute the metallic elements in their tissues. In turn, this distribution may have an important impact on phytoremediation. Here, we investigated the effects of different single-metal concentrations (10, 50, 100, and 300 MUmol L) of cadmium (Cd), nickel (Ni), and copper (Cu) on their subcellular distribution in L. var. (Indian mustard). At the applied concentration of 300 MUmol L, 98% of the Cu and 79% of Cd were retained in the roots, while Ni was distributed between leaves (32%), stems (29%), and roots (39%). The cell wall and soluble fractions were the dominant storage compartments for Cd and Cu in the stems and leaves, whereas the soluble fraction was the dominant storage compartment for Ni in stems and leaves. Scanning electron microscopy (SEM) X-ray micrographs showed a breakdown of epidermal, palisade, and spongy parenchyma cells following the 300 MUmol L Cd, Ni, and Cu treatment. A sigmoidal model is a powerful tool to describe the subcellular accumulation and tissue concentrations of Cd, Ni, and Cu following exposure to various concentrations of metals. The coefficients of determination () values for the description of the accumulation were high, although the membrane subcellular fraction did not fit the equation. Both the maximum accumulation capacity and the critical concentrations of metals were well described by the model. The results indicate that the use of a sigmoidal model is a promising method that could improve the understanding of metal accumulation at the subcellular level in Indian mustard. PMID- 24216366 TI - Phosphorus loss from a mixed land use catchment in northwest Spain. AB - This work examined P loss from a mixed land use catchment in northwest Spain and how it was related to hydrological factors. A stream draining a mixed land use catchment of 16 km in northwest Spain was monitored for 5 yr. Water samples were taken more frequently with increased stream flows. A total of 132 runoff events of different magnitudes were analyzed in this study. Mean annual P loss from the catchment was 11.5 kg km, about 68% being transported during runoff events, which only contributed to 29% of the flow. The contribution of runoff events to particulate P and dissolved P losses was 76 and 46% of total losses during the study period, respectively. A high interannual variability in P loss was observed, the differences being related to rainfall amount and distribution. At a seasonal scale, the highest P loads and concentrations were observed during rainy seasons; the lowest P loads occurred in summer because they occurred with stream flow. Particulate P accounted for the greatest proportion (74%) of transported P. There was a high variability in P transported between runoff events, with maximum discharge and discharge increase being the most important variables explaining total P concentration in these events through their effect on suspended sediment concentration. PMID- 24216367 TI - Effect of composting on the fate of steroids in beef cattle manure. AB - In this study, the fate of steroid hormones in beef cattle manure composting is evaluated. The fate of 16 steroids and metabolites was evaluated in composted manure from beef cattle administered growth promotants and from beef cattle with no steroid hormone implants. The fate of estrogens (primary detected as estrone), androgens, progesterone, and the fusarium metabolite and implant alpha-zearalanol was monitored in manure compost piles. First-order decay rates were calculated for steroid half-lives in compost and ranged from 8 d for androsterone to 69 d for 4-androstenedione. Other steroid concentration data could not be fit to first order decay models, which may indicate that microbial processes may result in steroid production or synthesis in composting systems. We demonstrate that composting is an effective strategy to remove steroid hormones from manure. Total steroid hormone removal in composted beef cattle manure ranged from 79 to 87%. PMID- 24216368 TI - Sorption, Leaching, and Surface Runoff of Beef Cattle Veterinary Pharmaceuticals under Simulated Irrigated Pasture Conditions. AB - The use of veterinary pharmaceuticals in beef cattle has led to concerns associated with the development of antibiotic resistance in bacteria and endocrine disruption in aquatic organisms. Despite the potential negative consequences, data on the transport and mitigation of pharmaceuticals in grazed watersheds with irrigated pasture are scarce. The objective of this study was to assess the transport of common beef cattle pharmaceuticals (oxytetracycline, chlortetracycline, and ivermectin) via surface runoff and leachate from manure amended to grass-vegetated soil boxes under irrigated pasture conditions. The transport of pharmaceuticals from animal manure in surface runoff and soil leachate was relatively low and appears to be limited by desorption and transport of pharmaceuticals entrained in the manure. In surface runoff, less than 4.2% of applied pharmaceuticals in manure (initial concentration: 0.2 mg kg of manure) was detected after 3 wk of irrigation. Concentrations of pharmaceuticals in surface runoff and leachate never exceeded 0.5 MUg L. The major portion of pharmaceuticals (up to 99%) was retained in the manure or in the soil directly beneath the manure application site. Based on the minimal transport of oxytetracycline, chlortetracycline, and ivermectin, the risk of significant transport for these targeted beef cattle pharmaceuticals to surface water and groundwater from manure on irrigated pasture appears to be relatively low. PMID- 24216369 TI - Potential contributions of mature prairie and turfgrass to phosphorus in urban runoff. AB - Urban vegetative plantings are considered desirable to mitigate and filter stormwater runoff and nonpoint-source pollution. Phosphorus fertilization of turfgrass may enhance P in urban runoff; however, the amount of P from nonfertilized, native vegetation that could potentially replace some turf is not known. This study was conducted to measure the relative contributions of nonfertilized, native prairie vegetation and fertilized turfgrass to runoff water and P loads. Six replicates of side-by-side mature urban prairie and turfgrass were monitored for mean annual runoff volumes and P loads, biomass production, vegetative nutrient composition, and changes in soil moisture. Vegetation type did not significantly affect seasonal or annual runoff volumes or P loads. The mean annual total P loads of 0.46 kg ha for prairie and 0.28 kg ha for turfgrass were significant and comparable to those reported by other researchers when studied separately. Total P concentrations in runoff water from prairie and turf vegetation were above USEPA limits, averaging 1.86 and 1.63 mg L, respectively, over 2 yr. Averaged across 2 yr, 78% of runoff P was collected when the soil was frozen. Biomass P reductions over the period of November to April were strongly related to quantities of runoff total P from frozen soil ( = 0.874). Phosphorus losses from urban areas appeared to be primarily correlated with runoff depth, not vegetation type, because correlation coefficients revealed 86 and 45% of the Year 1 and Year 2 total P loads were directly accounted for by runoff volumes. PMID- 24216370 TI - Update on the effects of a sierran wildfire on surface runoff water quality. AB - Wildfire has been shown to increase the short-term (1-3 yr) mobilization of mineral N and P in forest ecosystems of the Sierra Nevada Mountains and Lake Tahoe Basin. The ensuing effects on tributary and lake water quality are uncertain. The purpose of this investigation was to assess the impacts on runoff water quality over an intermediate time frame of 5 yr (2002-2007) after a wildfire event. Our design included fixed plots randomly placed within burned and unburned areas. Because each plot was sampled repeatedly during the study, we treated plots as repeated random effects in the analysis. We used a mixed model approach to analyze nutrient runoff concentrations and load for NH-N, NON and P in phosphate form (designated as ortho P or PO-P) where treatment (unburned vs. burned), time (pre-wildfire, post-wildfire year 1, year 2, etc.), and their interaction were fixed effects. Concentrations and loads of mineral N and P were higher in runoff from the burned areas immediately after wildfire. Because high water years may also contribute to higher runoff nutrient concentrations and loading, a wildfire followed by a high water year within the first season after a wildfire would likely have a much greater impact on runoff (and hence tributary) water quality than a wildfire followed by a low runoff water year. PMID- 24216371 TI - New Conceptual Model for Soil Treatment Units: Formation of Multiple Hydraulic Zones during Unsaturated Wastewater Infiltration. AB - Onsite wastewater treatment systems are commonly used in the United States to reclaim domestic wastewater. A distinct biomat forms at the infiltrative surface, causing resistance to flow and decreasing soil moisture below the biomat. To simulate these conditions, previous modeling studies have used a two-layer approach: a thin biomat layer (1-5 cm thick) and the native soil layer below the biomat. However, the effect of wastewater application extends below the biomat layer. We used numerical modeling supported by experimental data to justify a new conceptual model that includes an intermediate zone (IZ) below the biomat. The conceptual model was set up using Hydrus 2D and calibrated against soil moisture and water flux measurements. The estimated hydraulic conductivity value for the IZ was between biomat and the native soil. The IZ has important implications for wastewater treatment. When the IZ was not considered, a loading rate of 5 cm d resulted in an 8.5-cm ponding. With the IZ, the same loading rate resulted in a 9.5-cm ponding. Without the IZ, up to 3.1 cm d of wastewater could be applied without ponding; with the IZ, only up to 2.8 cm d could be applied without ponding. The IZ also plays a significant role in soil moisture distribution. Without the IZ, near-saturation conditions were observed only within the biomat, whereas near-saturation conditions extended below the biomat with the IZ. Accurate prediction of ponding is important to prevent surfacing of wastewater. The degree of water and air saturation influences pollutant treatment efficiency through residence time, volatility, and biochemical reactions. PMID- 24216372 TI - Biochemical methane potential of beef feedlot manure: impact of manure age and storage. AB - Methane capture and use from intensive livestock industries is relatively new, and there is limited chemical and kinetic degradation information available for beef feedlot manure in Australia or internationally. This paper evaluates the biochemical methane (CH) potential, apparent first-order hydrolysis rate coefficient, and losses in organic content of manure as it ages on feedlot pads and in stockpiles. Chemical characterization of fresh, pad, and stockpiled manure is assessed. Biochemical CH potential on volatile solids (VS) almost always decreased significantly from fresh to pad and from pad to stockpile, ranging (in mL CH g VS) from 230 to 360 in fresh manure, from 70 to 280 in pads, and from 60 to 200 in stockpiles. Kinetics of degradation also varied with manure age (fresh: 0.12 +/- 0.01 d; pad: 0.06 +/- 0.02 d; and stockpiled: 0.05 +/- 0.04 d). At least 50%, and up to 80%, of the original biochemical CH potential of the manure (i.e., degradable material) was lost on drying in pads, and the loss after stockpiling was much greater (>85%). The loss of N was 15 to 60% as manure dried on pads and was much greater after stockpiling (40-90%). Phosphorus loss, though lower than nitrogenous losses, was still significant (25-65% on pads and 35-85% in stockpiles). Although digestion of stockpiled manure is still feasible to generate energy, collection of fresh manure is important to maximize outcomes, with a possible order of magnitude increase in CH production achievable. PMID- 24216373 TI - Effluent Storage and Biomat Occurrence among Septic System Absorption Field Architectures in a Typic Fragiudult. AB - On-site wastewater treatment systems (OWTSs) are commonly used by households in areas of low population density to treat household wastewater and recycle it back to the environment. However, new absorption field products of differing architecture types have recently become available. A 3-yr field study was conducted in Bethel Heights, northwest Arkansas to assess several newer architecture types (i.e., chambers, polystyrene-aggregate, and gravel-less pipe) relative to the traditional pipe-and-gravel design under wet- and dry-soil conditions. Thirteen products of four different architecture types were installed in 46-cm-deep trenches in a Captina silt loam (fine-silty, siliceous, active, mesic Typic Fragiudult). Products were evaluated based on in-trench solution storage measured with an electronic water-level sensor approximately weekly from January 2009 through January 2012. Between May 2010 and January 2012, the thickness of any biomat formation was measured approximately weekly by insertion of a wooden dowel through in-trench monitoring ports. Architecture type alone did not affect ( > 0.05) in-trench solution storage. However, solution storage among individual products differed under wet- and dry-soil conditions ( < 0.05). When present, biomat thickness differed significantly ( < 0.05) among all four architecture types, ranging from 1.4 to 6.2 cm thick on average in the pipe-and aggregate and polystyrene-aggregate types, respectively. Regression analyses showed that biomat thickness increased in three products, did not change in nine products, and decreased in one product over time. Results showed that several currently approved alternative products had similar in-trench solution storage but that several alternative products also had greater solution storage than that of the traditional pipe-and-gravel system. With no observed effluent surfacing, the soil morphology approach appears to be adequate and appropriately environmentally conservative for assigning typical single-family loading rates to alternative OWTS products and to the traditional pipe-and-gravel system. PMID- 24216374 TI - Effect of treated domestic wastewater on soil physicochemical and microbiological properties. AB - A main concern with reuse of treated domestic wastewater (DWW) in irrigation is its possible effect on the soil. Few studies have focused on DWW treated in on site settings, which generally use low-tech systems that can be constructed and serviced locally. One such system is the recirculating vertical flow constructed wetland (RVFCW). The aim of this study was to assess short- to midterm effects of irrigation with DWW treated in the RVFCW. Four groups of plastic barrels, filled with a sandy loam soil, were irrigated for 36 mo with fresh water (FW), FW with added fertilizer, raw DWW, or DWW treated in the RVFCW followed by ultraviolet disinfection. Principal component analysis revealed that the soil irrigated with treated DWW had physicochemical properties similar to those irrigated with FW amended with fertilizer. Levels of surfactants in soil irrigated with treated DWW were identical to those expected from standard irrigation practices, abating concerns for possible changes in soil hydraulic properties. was not detected in the soil irrigated with treated DWW, demonstrating the importance of disinfection of treated effluents before reuse in irrigation. Furthermore, irrigation with treated DWW did not alter the bacterial community structure according to terminal restriction fragment analysis. This 3-yr study suggests that the practice of irrigation with RVFCW effluents is safe. Continuation of the experiment is required to determine whether longer-term irrigation might show a different pattern. PMID- 24216375 TI - Carbon sequestration in two created riverine wetlands in the midwestern United States. AB - Wetlands have the ability to accumulate significant amounts of carbon (C) and thus could provide an effective approach to mitigate greenhouse gas accumulation in the atmosphere. Wetland hydrology, age, and management can affect primary productivity, decomposition, and ultimately C sequestration in riverine wetlands, but these aspects of wetland biogeochemistry have not been adequately investigated, especially in created wetlands. In this study we investigate the ability of created freshwater wetlands to sequester C by determining the sediment accretion and soil C accumulation of two 15-yr-old created wetlands in central Ohio-one planted and one naturally colonized. We measured the amount of sediment and soil C accumulated over the parent material and found that these created wetlands accumulated an average of 242 g C m yr, 70% more than a similar natural wetland in the region and 26% more than the rate estimated for these same wetlands 5 yr before this study. The C sequestration of the naturally colonized wetland was 22% higher than that of the planted wetland (267 +/- 17 vs. 219 +/- 15 g C m yr, respectively). Soil C accrual accounted for 66% of the aboveground net primary productivity on average. Open water communities had the highest C accumulation rates in both wetlands. This study shows that created wetlands can be natural, cost-effective tools to sequester C to mitigate the effect of greenhouse gas emissions. PMID- 24216376 TI - Hydrologic connectivity to streams increases nitrogen and phosphorus inputs and cycling in soils of created and natural floodplain wetlands. AB - Greater connectivity to stream surface water may result in greater inputs of allochthonous nutrients that could stimulate internal nitrogen (N) and phosphorus (P) cycling in natural, restored, and created riparian wetlands. This study investigated the effects of hydrologic connectivity to stream water on soil nutrient fluxes in plots ( = 20) located among four created and two natural freshwater wetlands of varying hydrology in the Piedmont physiographic province of Virginia. Surface water was slightly deeper; hydrologic inputs of sediment, sediment-N, and ammonium were greater; and soil net ammonification, N mineralization, and N turnover were greater in plots with stream water classified as their primary water source compared with plots with precipitation or groundwater as their primary water source. Soil water-filled pore space, inputs of nitrate, and soil net nitrification, P mineralization, and denitrification enzyme activity (DEA) were similar among plots. Soil ammonification, N mineralization, and N turnover rates increased with the loading rate of ammonium to the soil surface. Phosphorus mineralization and ammonification also increased with sedimentation and sediment-N loading rate. Nitrification flux and DEA were positively associated in these wetlands. In conclusion, hydrologic connectivity to stream water increased allochthonous inputs that stimulated soil N and P cycling and that likely led to greater retention of sediment and nutrients in created and natural wetlands. Our findings suggest that wetland creation and restoration projects should be designed to allow connectivity with stream water if the goal is to optimize the function of water quality improvement in a watershed. PMID- 24216377 TI - Simultaneous removal of nitrate and sulfate from greenhouse wastewater by constructed wetlands. AB - This study evaluated the effectiveness of C-enriched subsurface-flow constructed wetlands in reducing high concentrations of nitrate (NO) and sulfate (SO) in greenhouse wastewaters. Constructed wetlands were filled with pozzolana, planted with common cattail (), and supplemented as follows: (i) constructed wetland with sucrose (CW+S), wetland units with 2 g L of sucrose solution from week 1 to 28; (ii) constructed wetland with compost (CW+C), wetland units supplemented with a reactive mixture of compost and sawdust; (iii) constructed wetland with compost and no sucrose (CW+CNS) from week 1 to 18, and constructed wetland with compost and sucrose (CW+CS) at 2 g L from week 19 to 28; and (iv) constructed wetland (CW). During 28 wk, the wetlands received a typical reconstituted greenhouse wastewater containing 500 mg L SO and 300 mg L NO. In CW+S, CW+C, and CW+CS, appropriate C:N ratio (7:3.4) and redox potential (-53 to 39 mV) for denitrification resulted in 95 to 99% NO removal. Carbon source was not a limiting factor for denitrification in C-enriched constructed wetlands. In CW+S and CW+CS, the dissolved organic carbon (DOC)/SO ratios of 0.36 and 0.28 resulted in high sulfate-reducing bacteria (SRB) counts and high SO removal (98%), whereas low activities were observed at DOC/SO ratios of 0.02 (CW) to 0.11 (CW+C, CW+CNS). On week 19, when organic C content was increased by sucrose addition in CW+CS, SRB counts increased from 2.80 to 5.11 log[CFU+1] mL, resulting in a level similar to the one measured in CW+S (4.69 log[CFU+1] mL). Consequently, high sulfate reduction occurred after denitrification, suggesting that low DOC (38-54 mg L) was the limiting factor. In CW, DOC concentration (9-10 mg L) was too low to sustain efficient denitrification and, therefore, sulfate reduction. Furthermore, the high concentration of dissolved sulfides observed in CW+S and CW+CS treated waters were eliminated by adding FeCl. PMID- 24216378 TI - An optode sensor array for long-term in situ oxygen measurements in soil and sediment. AB - Long-term measurements of molecular oxygen (O) dynamics in wetlands are highly relevant for understanding the effects of water level changes on net greenhouse gas budgets in these ecosystems. However, such measurements have been limited due to a lack of suitable measuring equipment. We constructed an O optode sensor array for long-term in situ measurements in soil and sediment. The new device consists of a 1.3-m-long, cylindrical, spear-shaped rod equipped with 10 sensor spots along the shaft. Each spot contains a thermocouple fixed with a robust fiberoptic O optode made by immobilizing a layer of Pt(II) meso tetra(pentafluorophenyl)porphine in polystyrene at the end of a 2-mm polymethyl methacrylate plastic fiber. Temperature and O optode readings are collected continuously by a data logger and a multichannel fiberoptic O meter. The construction and measuring characteristics of the sensor array system are presented along with a novel approach for temperature compensation of O optodes. During in situ application over several months in a peat bog, we used the new device to document pronounced variations in O distribution after marked shifts in water level. The measurements showed anoxic conditions below the water level but also diel variations in O concentrations in the upper layer presumably due to rhizospheric oxidation by the main vegetation The new field instrument thus enables new and more detailed insights to the in situ O dynamics in wetlands. PMID- 24216379 TI - Introducing the GRACEnet/REAP Data Contribution, Discovery, and Retrieval System. AB - Difficulties in accessing high-quality data on trace gas fluxes and performance of bioenergy/bioproduct feedstocks limit the ability of researchers and others to address environmental impacts of agriculture and the potential to produce feedstocks. To address those needs, the GRACEnet (Greenhouse gas Reduction through Agricultural Carbon Enhancement network) and REAP (Renewable Energy Assessment Project) research programs were initiated by the USDA Agricultural Research Service (ARS). A major product of these programs is the creation of a database with greenhouse gas fluxes, soil carbon stocks, biomass yield, nutrient, and energy characteristics, and input data for modeling cropped and grazed systems. The data include site descriptors (e.g., weather, soil class, spatial attributes), experimental design (e.g., factors manipulated, measurements performed, plot layouts), management information (e.g., planting and harvesting schedules, fertilizer types and amounts, biomass harvested, grazing intensity), and measurements (e.g., soil C and N stocks, plant biomass amount and chemical composition). To promote standardization of data and ensure that experiments were fully described, sampling protocols and a spreadsheet-based data-entry template were developed. Data were first uploaded to a temporary database for checking and then were uploaded to the central database. A Web-accessible application allows for registered users to query and download data including measurement protocols. Separate portals have been provided for each project (GRACEnet and REAP) at nrrc.ars.usda.gov/slgracenet/#/Home and nrrc.ars.usda.gov/slreap/#/Home. The database architecture and data entry template have proven flexible and robust for describing a wide range of field experiments and thus appear suitable for other natural resource research projects. PMID- 24216380 TI - Controlling runoff from subtropical pastures has differential effects on nitrogen and phosphorus loads. PMID- 24216381 TI - Trace elements in feed, manure, and manured soils. PMID- 24216382 TI - Electroencephalographic monitoring in comatose survivors of cardiac arrest. AB - Electroencephalography (EEG) monitoring is an important tool in the management of comatose survivors of cardiac arrest. The results serve to predict the neurological outcome, identify postanoxic status epilepticus, and assess the effectiveness of antiepileptic treatments. Continuous EEG monitoring might seem the most attractive option but is costly and requires the continuous availability of an expert to interpret the findings. Alvarez and colleagues compared repeated standard EEG to continuous EEG monitoring in comatose survivors of cardiac arrest. They found close agreement between these two strategies. However, their results do not constitute evidence of similar performance. In comatose survivors of cardiac arrest, repeated standard EEG should be used only when continuous EEG monitoring is unavailable. PMID- 24216383 TI - Novel sounds as a psychophysiological measure of listening effort in older listeners with and without hearing loss. AB - OBJECTIVE: To investigate whether task-irrelevant novel sounds presented during an auditory task can provide information about the level of listening effort. METHODS: Event-related potentials (ERPs) were recorded for novel sounds presented during two Experiments, a frequency discrimination task and a speech-perception in-noise (SPIN) test, each with varying degrees of task difficulty (easy, medium, hard). Difficulty was adjusted to the individual frequency discrimination threshold and 50% speech recognition signal-to-noise ratio (SNR), respectively. Older listeners (age range 60-86 years) with either normal hearing for their age or a mild-to-moderate hearing loss participated. RESULTS: Amplitudes of Novelty P3 and late positive potential (LPP) increased with increasing task difficulty, whereas amplitudes of N1 and N2 decreased. Participants with hearing loss had significantly larger LPP amplitudes in the easy condition of the SPIN test than did normal-hearing listeners. Most correlations between ERP amplitudes and behavioral data were not significant suggesting that listening effort is not a simple equivalent of behavioral performance. CONCLUSIONS: LPP amplitude appeared to be the most sensitive component for capturing listening effort reflecting the arousal level of the listener. SIGNIFICANCE: ERPs to novel sounds could be easily recorded during hearing tests and provide an objective physiological measure of listening effort, thus supplementing behavioral performance data. PMID- 24216384 TI - Attention orienting dysfunction with preserved automatic auditory change detection in migraine. AB - OBJECTIVE: To investigate automatic event-related potentials (ERPs) to an auditory change in migraine patients. METHODS: Auditory ERPs were recorded in 22 female patients suffering from menstrually-related migraine and in 20 age-matched control subjects, in three sessions: in the middle of the menstrual cycle, before and during menses. In each session, 200 trains of tone-bursts each including two duration deviants were presented in a passive listening condition. RESULTS: In all sessions, duration deviance elicited a mismatch negativity (MMN) showing no difference between the two groups. However, migraine patients showed an increased N1 orienting component to all incoming stimuli and a prolonged N2b to deviance. They also presented a different modulation of P3a amplitude along the menstrual cycle, which tended to normalise during migraine attacks. None of the studied ERP components showed a default of habituation. CONCLUSIONS: This passive paradigm highlighted increased automatic attention orienting to auditory changes but normal auditory sensory processing in migraineurs. SIGNIFICANCE: Our observations suggest normal auditory processing up to attention triggering but enhanced activation of attention-related frontal networks in migraineurs. PMID- 24216385 TI - Standardized quality performance metrics: beware of the pitfalls. PMID- 24216386 TI - Novel technique to visualise pharyngeal free flap reconstructions. PMID- 24216388 TI - Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1. AB - AIMS: Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. METHODS AND RESULTS: In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca(2+) cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2(-/-)) mice. Casq2(-/-) mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca(2+) cycling, including abnormal Ca(2+) release, periods of significantly elevated diastolic Ca(2+) levels leading to pauses and unstable pacemaker rate. Importantly, Ca(2+) cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca(2+) transient upstrokes throughout the atrial pacemaker complex. CONCLUSIONS: Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca(2+) release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID- 24216389 TI - The gut microbiome as novel cardio-metabolic target: the time has come! AB - Recent studies reveal a potential contribution of intestinal microbes in the expression of certain human cardio-metabolic diseases. The mechanisms through which intestinal microbiota and/or their metabolic products alter systemic homoeostasis and cardio-metabolic disease risks are just beginning to be dissected. Intervention studies in humans aiming to either selectively alter the composition of the intestinal microbiota or to pharmacologically manipulate the microbiota to influence production of their metabolites are crucial next steps. The intestinal microbiome represents a new potential therapeutic target for the treatment of cardio-metabolic diseases. PMID- 24216390 TI - Natriuretic peptide-guided heart failure management. AB - The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a 'guide' for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach. PMID- 24216391 TI - State-of-the-art treatment of hypertension: established and new drugs. AB - The treatment of essential hypertension is based essentially on the prescription of four major classes of antihypertensive drugs, i.e. blockers of the renin- angiotensin system, calcium channel blockers, diuretics and beta-blockers. In recent years, very few new drug therapies of hypertension have become available. Therefore, it is crucial for physicians to optimize their antihypertensive therapies with the drugs available on the market. In each of the classes of antihypertensive drugs, questions have recently been raised: are angiotensin converting enzyme (ACE) inhibitors superior to angiotensin II receptor blockers (ARB)? Is it possible to reduce the incidence of peripheral oedema with calcium antagonists? Is hydrochlorothiazide really the good diuretic to use in combination therapies? The purpose of this review is to discuss these various questions in the light of the most recent clinical studies and meta-analyses. These latter suggest that ACE inhibitors and ARB are equivalent except for a better tolerability profile of ARB. Third generation calcium channel blockers enable to reduce the incidence of peripheral oedema and chlorthalidone is certainly more effective than hydrochlorothiazide in preventing cardiovascular events in hypertension. At last, studies suggest that drug adherence and long term persistence under therapy is one of the major issues in the actual management of essential hypertension. PMID- 24216392 TI - Left ventricular lead implantation guided by sensor-based electromagnetic navigation in a patient with L-transposition of the great arteries. PMID- 24216393 TI - Gender differences in circumstances surrounding first injection experience of rural injection drug users in the United States. AB - BACKGROUND: Research has demonstrated that there can be substantial gender differences in circumstances surrounding initiation of injection drug use; however, little is known about the gendered dynamics of first injection in rural areas where syringe exchange is inaccessible or among those who predominantly inject prescription medications. The present study examines gender differences in first injection experience among rural residents who predominantly inject prescription opioids. METHODS: Interview-administered questionnaires collected data from a sample of injection drug users (n=394) recruited from Appalachian Kentucky using respondent-driven sampling. RESULTS: Women were more likely to have initiated injection due to social-pressure (p=0.001), received the drugs as a gift (p=0.011), initiated in their partner's home (p=0.004) and in their partner's presence (p<0.001), been injected by their partner (p<0.001), used an unclean syringe (p=0.026), and received the syringe from their partner (p<0.001). Women were also more likely to report having engaged in sexual intercourse before or after initiation (p<0.001). Men were more likely to have personally purchased the drugs (p=0.002), to have acquired the syringe from a pharmacy/clinic (p=0.004), and to have injected with a friend (p=0.001) or family member (p=0.020). Men were also more likely to have a friend administer the first injection (p=0.007). CONCLUSIONS: In this population of rural drug users, notable gender differences in injection initiation were observed. Social pressure played a more substantial role in women's first injection experience, and male partners had an integral role in women's initiation. PMID- 24216394 TI - Incidence and risk factors for perioperative visual loss after spinal fusion. AB - BACKGROUND CONTEXT: Perioperative visual loss (POVL) is a rare but devastating complication that may follow spinal surgeries. The incidence of POVL after spinal fusion is not well characterized during the past decade. PURPOSE: A population based database was analyzed to characterize the incidence and risk factors for POVL associated with spinal fusion surgery on a national level. STUDY DESIGN: This study consisted of a retrospective database analysis. PATIENT SAMPLE: A total of 541,485 patients from the Nationwide Inpatient Sample (NIS) database were included in the study. OUTCOME MEASURES: Study outcome measures included incidence of POVL, length of stay (LOS), in-hospital costs, mortality, and POVL risk factors. METHODS: Data from the NIS were obtained from 2002 to 2009. Patients undergoing spinal fusion for degenerative pathologies were identified. Patient demographics, comorbidities, LOS, costs, and mortality were assessed. Statistical analyses were conducted using an independent t test for discrete variables and the chi-square test for categorical data. Binomial logistic regression was used to identify independent predictors of POVL. A p value of less than or equal to .001 was used to denote statistical significance. No funds were received by any of the authors for production of this study. RESULTS: A total of 541,485 spinal fusions were identified in the United States from 2002 to 2009. The overall incidence of POVL was 1.9 events per 10,000 cases. Of patients who had POVL, 56.2% underwent surgery for a diagnosis of spinal deformity. Patients with POVL were significantly younger on average compared with unaffected patients (37.6 years vs. 52.4 years; p<.001). Length of stay and hospital costs doubled for patients with POVL (p<.001). Logistic regression analysis demonstrated that independent predictors of visual loss were deformity surgery (odds ratio [OR]=6.1), diabetes mellitus with end organ damage (OR=13.1), and paralysis (OR=6.0, p<.001). CONCLUSIONS: Our findings demonstrated an overall POVL incidence of 1.9 events per 10,000 spinal fusions. Patients undergoing thoracic fusion for deformity correction accounted for the majority of cases of POVL. Despite being a rare complication after spinal fusion, POVL is an adverse event that may not be entirely preventable. Patients undergoing long-segment fusions for deformity and those with certain risk factors should be counseled regarding the risks of POVL. PMID- 24216395 TI - Oswestry Disability Index is a better indicator of lumbar motion than the Visual Analogue Scale. AB - BACKGROUND CONTEXT: Lumbar pathology is often associated with axial pain or neurologic complaints. It is often presumed that such pain is associated with decreased lumbar motion; however, this correlation is not well established. The utility of various outcome measures that are used in both research and clinical practice have been studied, but the connection with range of motion (ROM) has not been well documented. PURPOSE: The current study was performed to assess objectively the postulated correlation of lumbar complaints (based on standardized outcome measures) with extremes of lumbar ROM and functional ROM (fROM) with activities of daily living (ADLs) as assessed with an electrogoniometer. STUDY DESIGN/SETTING: This study was a clinical cohort study. PATIENT SAMPLE: Subjects slated to undergo a lumbar intervention (injection, decompression, and/or fusion) were enrolled voluntarily in the study. OUTCOME MEASURES: The two outcome measures used in the study were the Visual Analogue Scale (VAS) for axial extremity, lower extremity, and combined axial and lower extremity, as well as the Oswestry Disability Index (ODI). METHODS: Pain and disability scores were assessed with the VAS score and ODI. A previously validated electrogoniometer was used to measure ROM (extremes of motion in three planes) and fROM (functional motion during 15 simulated activities of daily living). Pain and disability scores were analyzed for statistically significant association with the motion assessments using linear regression analyses. RESULTS: Twenty-eight men and 39 women were enrolled, with an average age of 55.6 years (range, 18-79 years). The ODI and VAS were associated positively (p<.001). Combined axial and lower extremity VAS scores were associated with lateral and rotational ROM (p<.05), but not with flexion/extension or any fROM. Similar findings were noted for separately analyzed axial and lower extremity VAS scores. On the other hand, the ODI correlated inversely with ROM in all planes, and fROM in at least one plane for 10 of 15 ADLs (p<.05). CONCLUSIONS: Extremes of lumbar motion and motions associated with ADLs are of increasing clinical interest. Although the ODI and VAS are associated with each other, the ODI appears to be a better predictor of these motion parameters than the VAS (axial extremity, lower extremity, or combined) and may be more useful in the clinical setting when considering functional movement parameters. PMID- 24216396 TI - Associations between lumbosacral transitional anatomy types and degeneration at the transitional and adjacent segments. AB - BACKGROUND CONTEXT: The relation between specific types of lumbosacral transitional vertebra and the degree of degeneration at and adjacent to the transitional level is unclear. It is also unknown whether the adjacent cephalad segment to a transitional vertebra is prone to greater degeneration than a normal L5-S1 level. PURPOSE: The purpose of this study was to evaluate the relation between specific lumbosacral transitional vertebra subtypes according to the Castellvi classification, and to determine the severity of degeneration at the transitional level and the adjacent cephalad segment. STUDY DESIGN: This study was a retrospective review. PATIENT SAMPLES: Ninety-two subjects with lumbosacral transitional vertebra grade 2 or higher and 94 control subjects without were retrieved from a picture archiving and communication system (PACS) search. OUTCOME MEASURES: Disc degeneration parameters at the transitional and at the adjacent cephalad level were measured. METHODS: After institutional review board approval, 92 subjects (42 men; mean age, 57+/-16 years) with lumbosacral transitional vertebra grade 2 or higher and 94 control subjects (41 men; mean age, 51+/-16 years) without were retrieved from a PACS search. Degeneration of the last two segments of the lumbar spine was quantified using the Pfirrmann and Modic classifications, along with documentation of annular tears, disc herniations, and disc height, and were compared between the two groups. Furthermore, L5-S1 levels in the control subjects were compared with the adjacent cephalad segments of the transitional vertebrae for the same parameters. RESULTS: Although the control subjects, at L5-S1, had moderate to severe degeneration by Pfirrmann grades (31%) and Modic changes ([MC] 20%), in comparison, the discs at the transitional level of the lumbosacral transitional vertebra group demonstrated significant less degeneration (3% and 1%, respectively; each p<.05). The adjacent cephalad segments of the lumbosacral transitional vertebra group showed significantly greater degeneration (Pfirrmann grade 5, 39%; MC, 30%) compared with the L4-L5 level in control subjects (16% and 11%, respectively; each p<.05). The severity of disc degeneration using all parameters correlated with the type of lumbosacral transitional vertebra. The degree of degeneration of L5-S1 in control subjects was similar to the adjacent cephalad segment in lumbosacral transitional vertebrae. CONCLUSION: Increasing the mechanical connection of a lumbosacral transitional vertebra protects the disc at the transitional level and predisposes the adjacent cephalad segment to greater degeneration. The adjacent cephalad segment had a comparable degree of degeneration as the L5-S1 level in control subjects. PMID- 24216397 TI - The incidence and patterns of hardware failure after separation surgery in patients with spinal metastatic tumors. AB - BACKGROUND CONTEXT: Spine metastases occur frequently in patients with cancer. A variety of surgical approaches, including anterior transcavitary, lateral extracavitary, posterolateral, and/or combined techniques are used for spinal cord decompression and restoration of spinal stability. The incidence of symptomatic hardware failure is unknown for the majority of these approaches. PURPOSE: The purpose of this study was to determine the incidence of symptomatic hardware failure and the associated risk factors in patients with metastatic epidural spinal cord compression (MESCC). STUDY DESIGN/SETTING: This was a retrospective study. PATIENT SAMPLE: The current series analyzes a cohort of 318 patients who underwent separation surgery, which involves single-stage posterolateral decompression and posterior segmental instrumentation for MESCC. OUTCOME MEASURES: The event of interest was hardware failure; the competing event was death resulting from any cause. All patients were monitored for survival analysis. A competing risk analysis was conducted to examine univariately a number of potential risk factors associated with hardware failure, including junctional level, gender, construct length, and the presence or absence of prior chest wall resection. METHODS: A retrospective analysis and chart review were performed for 318 consecutive patients who underwent posterolateral decompression and posterior screw-rod fixation without supplemental anterior fixation from March 2004 to June 2011 at our institution. The median follow-up time for survivors without hardware failure was 399 days (range, 9-2,828), with a mean operative time of 3 hours. A total of 78% of patients died during the 7-year study period. RESULTS: Of the 318 patients, nine (2.8%) exhibited signs and symptoms of hardware failure and required revision of the instrumentation. Patients with chest wall resection and those with initial construct length greater than six contiguous spinal levels exhibited a statistically significantly higher risk of symptomatic hardware failure than their counterparts. We observed a trend toward an increased risk of failure in women compared with men (p=.09). CONCLUSIONS: The incidence of hardware failure is low in patients with MESCC who undergo posterolateral decompression and posterior screw-rod instrumentation. Moreover, the short operative time and low morbidity profile associated with this approach make it a reliable and acceptable method for the surgical treatment of MESCC. Patients with constructs spanning six or more levels or those with prior chest wall resection are at higher risk for instrumentation failure. PMID- 24216398 TI - A systematic review of diagnostic imaging use for low back pain in the United States. AB - BACKGROUND CONTEXT: Various studies have reported on the increasing use and costs of diagnostic imaging for low back pain (LBP) in the United States. However, it is unclear whether the methods used in these studies allowed for meaningful comparisons or whether the reported use data can be used to develop evidence based use benchmarks. PURPOSE: The primary purpose of this study was to review previous estimates of the use of diagnostic imaging for LBP in the United States. STUDY DESIGN/SETTING: The study design is a systematic review of published literature. METHODS: A search through May 2012 was conducted using keywords and free text terms related to health services and LBP in Medline and Health Policy Reference; results were screened for relevance independently, and full-text studies were assessed for eligibility. Only studies published in English since the year 2000 reporting on use of diagnostic imaging for LBP using claims data from the United States were included. Reporting quality was assessed using a modified Downs and Black tool for observational studies. RESULTS: The search strategy yielded 1,102 citations, seven of which met the criteria for eligibility. Studies reported use from commercial health plans (N=4) and Medicare (N=3), with sample sizes ranging from 13,760 to 740,467 members with LBP from specific states or across the United States. The number of diagnostic codes used to identify nonspecific LBP ranged from 2 to 66; other heterogeneity was noted in the methods used across these studies. In commercial health plans, use of radiography occurred in 12.0% to 32.2% of patients with LBP, magnetic resonance imaging (MRI) was used in 16.0% to 21.0%, computed tomography (CT) was used in 1.4% to 3.0%, and MRI and/or CT was used in 10.9% to 16.1%. Findings in Medicare populations were 22.9% to 48.2% for radiography, 11.6% for MRI, and 10.4% to 16.3% for MRI and/or CT. CONCLUSIONS: The reported use of diagnostic imaging for LBP varied across the studies reviewed; differences in methodology made meaningful comparisons difficult. Standardizing methods for performing and reporting analyses of claims data related to use could facilitate efforts by third-party payers, health care providers, and researchers to identify and address the perceived overuse of diagnostic imaging for LBP. PMID- 24216399 TI - Face mask removal is safer than helmet removal for emergent airway access in American football. AB - BACKGROUND CONTEXT: In cases of possible cervical spine injury, medical professionals must be prepared to achieve rapid airway access while concurrently restricting cervical spine motion. Face mask removal (FMR), rather than helmet removal (HR), is recommended to achieve this. However, no studies have been reported that compare FMR directly with HR. PURPOSE: The purpose of this study was to compare motion, time, and perceived difficulty in two commonly used American football helmets between FMR and HR techniques, and when helmet air bladders were deflated before HR compared with inflated scenarios. STUDY DESIGN/SETTING: The study incorporated a repeated measures design and was performed in a controlled laboratory setting. PARTICIPANTS: Participants included 22 certified athletic trainers (15 men and seven women; mean age, 33.9+/-10.5 years; mean experience, 11.4+/-10.0 years; mean height, 172+/-9.4 cm; mean mass, 76.7+/-14.9 kg). All participants were free from upper extremity or central nervous system pathology for 6 months and provided informed consent. OUTCOME MEASURES: Dependent variables included head excursion in degrees (computed by subtracting the minimum position from the maximum position) in each of the three planes (sagittal, frontal, transverse), time to complete the required task, and ratings of perceived exertion. To address our study purposes, we used two-by-two repeated-measures analysis of variance (removal technique*helmet type, helmet type*deflation status) for each dependent variable. METHODS: Independent variables consisted of removal technique (FMR and HR), helmet type (Riddell Revolution IQ [RIQ] and VSR4), and helmet deflation status (deflated [D], inflated, [I]). After familiarization, participants conducted two successful trials for each of six conditions in random order (RIQ-FMR, VSR4-FMR, RIQ-HR-D, VSR4-HR-D, RIQ-HR-I, and VSR4-HR-I). Face masks, helmets, and shoulder pads were removed from a live model wearing a properly fitted helmet and shoulder pads. The participant and an investigator stabilized the model's head. A six-camera three dimensional motion system and a three-point one-segment marker set were used to record motion of the head. RESULTS: Face mask removal resulted in less motion in all three planes, required less completion time, and was easier to perform than HR. The RIQ helmet resulted in less frontal plane motion and less time to task completion, and was easier to remove than VSR4 helmets. Inflated helmets regardless of helmet type-required less removal time but did not result in greater cervical spine motion or difficulty. CONCLUSIONS: It is safer to remove the face mask in the prehospital setting for the potential spine-injured American football player than to remove the helmet, based on results from both a traditional and newer football helmet designs. Deflating the air bladder inside the helmet does not provide an advantage. PMID- 24216400 TI - Reliability and measurement error of sagittal spinal motion parameters in 220 patients with chronic low back pain using a three-dimensional measurement device. AB - BACKGROUND CONTEXT: A basic premise for any instrument measuring spinal motion is that reliable outcomes can be obtained on a relevant sample under standardized conditions. PURPOSE: The purpose of this study was to assess the overall reliability and measurement error of regional spinal sagittal plane motion in patients with chronic low back pain (LBP), and then to evaluate the influence of body mass index, examiner, gender, stability of pain, and pain distribution on reliability and measurement error. STUDY DESIGN/SETTING: This study comprises a test-retest design separated by 7 to 14 days. PATIENT SAMPLE: The patient cohort consisted of 220 individuals with chronic LBP. OUTCOME MEASURES: Kinematics of the lumbar spine were sampled during standardized spinal extension-flexion testing using a 6-df instrumented spatial linkage system. METHODS: Test-retest reliability and measurement error were evaluated using interclass correlation coefficients (ICC(1,1)) and Bland-Altman limits of agreement (LOAs). RESULTS: The overall test-retest reliability (ICC(1,1)) for various motion parameters ranged from 0.51 to 0.70, and relatively wide LOAs were observed for all parameters. Reliability measures in patient subgroups (ICC(1,1)) ranged between 0.34 and 0.77. In general, greater (ICC(1,1)) coefficients and smaller LOAs were found in subgroups with patients examined by the same examiner, patients with a stable pain level, patients with a body mass index less than below 30 kg/m(2), patients who were men, and patients in the Quebec Task Force classifications Group 1. CONCLUSIONS: This study shows that sagittal plane kinematic data from patients with chronic LBP may be sufficiently reliable in measurements of groups of patients. However, because of the large LOAs, this test procedure appears unusable at the individual patient level. Furthermore, reliability and measurement error varies substantially among subgroups of patients. PMID- 24216401 TI - Interaction of potential risk factors for cancer. PMID- 24216402 TI - Black hole in the spine. PMID- 24216403 TI - Intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar surgery: a double-blinded, randomized, placebo-controlled clinical trial. AB - BACKGROUND CONTEXT: Analgesic effect of lidocaine infusion on postoperative pain. PURPOSE: The aim of this study was to evaluate the analgesic effect of lidocaine infusion on postoperative pain after lumbar microdiscectomy. STUDY DESIGN: This study used a prospective, randomized, double-blinded, and placebo-controlled clinical trial. PATIENT SAMPLE: Fifty-one patients participated in this randomized, double-blinded study. OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) (0-100 mm) pain score at 4 hours after surgery. The secondary outcomes were the VAS pain score at 2, 8, 12, 24, and 48 hours after surgery, the frequency with which patients pushed the button (FPB) of the patient controlled analgesia system, and the fentanyl consumption at 2, 4, 8, 12, 24, and 48 hours after surgery. Other outcomes were satisfaction scores regarding pain control and the overall recovery process, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (HS). METHODS: Preoperatively and throughout the surgery, Group L received intravenous lidocaine infusion (a 1.5 mg/kg bolus followed by a 2-mg/kg/h infusion until the end of the surgical procedure) and Group C received normal saline infusion as a placebo. RESULTS: The VAS scores and fentanyl consumption were significantly lower in Group L compared with Group C except at 48 h after surgery (p<.05). Total fentanyl consumption, total FPB, length of HS, and satisfaction scores were also significantly lower in Group L compared with Group C (p<.05). CONCLUSIONS: Intraoperative systemic infusion of lidocaine decreases pain perception during microdiscectomy, thus reducing the consumption of opioid and the severity of postoperative pain. This effect contributes to reduce the length of HS. PMID- 24216404 TI - Delirium in elderly vascular surgery patients. AB - The elderly represent a large percentage of patients seen in departments of vascular surgery. Delirium is a frequent perioperative complication in this population and contributes to increased morbidity and mortality. Prevention of problems associated with mental confusion rests in identifying comorbidities, their severity, and the risk factors associated with delirium syndrome. The aging of our population implies management of increasing numbers of older patients who often have concomitant pathologies and, consequently, polypharmacy. Optimization of their management rests on collaboration between surgeons, anesthetists, and geriatrists. PMID- 24216405 TI - Ascending aorto-superior mesenteric artery bypass as a surgical option for revascularization in mesenteric ischemia associated with type B aortic dissection. AB - We report the case of an acute ischemia of the superior mesenteric artery (SMA) after endovascular fenestration of a complicated acute type B aortic dissection. An initial attempt for endovascular revascularization of the SMA failed, and an ascending aorto-superior mesenteric artery bypass was urgently performed to salvage the small bowel. Surgery of patients in these specific settings is more complex because an adequate, more distal inflow vessel is often not present due to the dissected aorta and iliac arteries. This surgical option could be lifesaving and should be part of the vascular surgeon's armamentarium. PMID- 24216406 TI - Deep venous thrombosis in a young woman with hypoplastic inferior vena cava. AB - We present a 33-year-old woman with deep venous thrombosis of the left iliac vein and the left lower limb. A computed tomography scan of her abdomen revealed a hypoplastic inferior vena cava and agenesis of the right kidney. Congenital anomalies of the inferior vena cava are uncommon and are sometimes an unrecognized cause of deep venous thrombosis. PMID- 24216407 TI - How reading acquisition changes children's spoken language network. AB - To examine the influence of age and reading proficiency on the development of the spoken language network, we tested 6- and 9-years-old children listening to native and foreign sentences in a slow event-related fMRI paradigm. We observed a stable organization of the peri-sylvian areas during this time period with a left dominance in the superior temporal sulcus and inferior frontal region. A year of reading instruction was nevertheless sufficient to increase activation in regions involved in phonological representations (posterior superior temporal region) and sentence integration (temporal pole and pars orbitalis). A top-down activation of the left inferior temporal cortex surrounding the visual word form area, was also observed but only in 9year-olds (3years of reading practice) listening to their native language. These results emphasize how a successful cultural practice, reading, slots in the biological constraints of the innate spoken language network. PMID- 24216408 TI - Environmental challenges threatening the growth of urban agriculture in the United States. AB - Urban agriculture, though often difficult to define, is an emerging sector of local food economies in the United States. Although urban and agricultural landscapes are often integrated in countries around the world, the establishment of mid- to large-scale food production in the U.S. urban ecosystem is a relatively new development. Many of the urban agricultural projects in the United States have emerged from social movements and nonprofit organizations focused on urban renewal, education, job training, community development, and sustainability initiatives. Although these social initiatives have traction, critical knowledge gaps exist regarding the science of food production in urban ecosystems. Developing a science-based approach to urban agriculture is essential to the economic and environmental sustainability of the movement. This paper reviews abiotic environmental factors influencing urban cropping systems, including soil contamination and remediation; atmospheric pollutants and altered climatic conditions; and water management, sources, and safety. This review paper seeks to characterize the limited state of the science on urban agricultural systems and identify future research questions most relevant to urban farmers, land-use planners, and environmental consultants. PMID- 24216409 TI - Primary isolation of shiga toxigenic from environmental sources. AB - Since the time of the first microbe hunters, primary culture and isolation of bacteria has been a foundation of microbiology. Like other microbial methods, bacterial culture and isolation methodologies continue to develop. Although fundamental concepts like selection and enrichment are as relevant today as they were over 100 yr ago, advances in chemistry, molecular biology and bacterial ecology mean that today's culture and isolation techniques serve additional supporting roles. The primary isolation of Shiga toxigenic (STEC) from environmental sources relies on enriching the target while excluding extensive background flora. Due to the complexity of environmental substrates, no single method can be recommended; however, common themes are discussed. Brilliant Green Bile Broth, with or without antibiotics, is one of many broths used successfully for selective STEC enrichment. Stressed cells may require a pre-enrichment recovery step in a nonselective broth such as buffered peptone water. After enrichment, immunomagnetic separation with serotype specific beads drastically increases the chances for recovery of STEC from environmental or insect sources. Some evidence suggests that acid treating the recovered beads can further enhance isolation. Although it is common in human clinical, food safety, and water quality applications to plate the recovered beads on Sorbitol MacConkey Agar, other chromogenic media, such as modified CHROMagar, have proven helpful in field and outbreak applications, allowing the target to be distinguished from the numerous background flora. Optimum conditions for each sample and target must be determined empirically, highlighting the need for a better understanding of STEC ecology. PMID- 24216410 TI - Phosphorus legacy: overcoming the effects of past management practices to mitigate future water quality impairment. AB - The water quality response to implementation of conservation measures across watersheds has been slower and smaller than expected. This has led many to question the efficacy of these measures and to call for stricter land and nutrient management strategies. In many cases, this limited response has been due to the legacies of past management activities, where sinks and stores of P along the land-freshwater continuum mask the effects of reductions in edge-of-field losses of P. Accounting for legacy P along this continuum is important to correctly apportion sources and to develop successful watershed remediation. In this study, we examined the drivers of legacy P at the watershed scale, specifically in relation to the physical cascades and biogeochemical spirals of P along the continuum from soils to rivers and lakes and via surface and subsurface flow pathways. Terrestrial P legacies encompass prior nutrient and land management activities that have built up soil P to levels that exceed crop requirements and modified the connectivity between terrestrial P sources and fluvial transport. River and lake P legacies encompass a range of processes that control retention and remobilization of P, and these are linked to water and sediment residence times. We provide case studies that highlight the major processes and varying timescales across which legacy P continues to contribute P to receiving waters and undermine restoration efforts, and we discuss how these P legacies could be managed in future conservation programs. PMID- 24216411 TI - Tracking short-term effects of nitrogen-15 addition on nitrous oxide fluxes using fourier-transform infrared spectroscopy. AB - Synthetic fertilizer N additions to soils have significantly increased atmospheric NO concentrations, and advanced methods are needed to track the amount of applied N that is transformed to NO in the field. We have developed a method for continuous measurement of NO isotopologues (NNO, NNO, NNO, and NNO) following 0.4 and 0.8 g N m of N-labeled substrate as KNO or urea [CO(NH)] using Fourier-transform infrared (FTIR) spectroscopy. We evaluated this method using two 4-wk experimental trials on a coastal floodplain site near Nowra, New South Wales, Australia, which is managed for silage production. We deployed an automated five-chamber system connected to a portable FTIR spectrometer with multipass cell to measure NO isotopologue fluxes. Emissions of all isotopologues were evident immediately following N addition. All isotopologues responded positively to rainfall events, but only for 7 to 10 d following N addition. Cumulative N-NO fluxes (sum of the three N isotopologues) per chamber for the 14 d following N addition ranged from 1.5 to 10.3 mg N m. Approximately 1% (range 0.7-1.9%) of the total amount of N applied was emitted as NO. Repeatability (1sigma) for all isotopologue measurements was better than 0.5 nmol mol for 1-min average concentration measurements, and minimum detectable fluxes for each isotopologue were <0.1 ng N m s. The results indicate that the portable FTIR spectroscopic technique can effectively trace transfer of N to the atmosphere as NO after N addition, allowing powerful quantification of NO emissions under field conditions. PMID- 24216412 TI - Particulate emissions from a beef cattle feedlot using the flux-gradient technique. AB - Data on air emissions from open-lot beef cattle () feedlots are limited. This research was conducted to determine fluxes of particulate matter with an aerodynamic diameter <=10 MUm (PM) from a commercial beef cattle feedlot in Kansas using the flux-gradient technique, a widely used micrometeorological method for air emissions from open sources. Vertical PM concentration profiles and micrometeorological parameters were measured at the feedlot using tapered element oscillating microbalance PM samplers and eddy covariance instrumentations (i.e., sonic anemometer and infrared hygrometer), respectively, from May 2010 through September 2011, representing feedlot conditions with air temperatures ranging from -24 to 39 degrees C. Calculated hourly PM fluxes varied diurnally and seasonally, ranging up to 272 mg m h, with an overall median of 36 mg m h. For warm conditions (air temperature of 21 +/- 10 degrees C), the highest hourly PM fluxes (range 116-146 mg m h) were observed during the early evening period, from 2000 to 2100 h. For cold conditions (air temperature of -2 +/- 8 degrees C), the highest PM fluxes (range 14-27 mg m h) were observed in the afternoon, from 1100 to 1500 h. Changes in the hourly trend of PM fluxes coincided with changes in friction velocity, air temperature, sensible heat flux, and surface roughness. The PM emission was also affected by the pen surface water content, where a water content of at least 20% (wet basis) would be sufficient to effectively reduce PM emissions from pens by as much as 60%. PMID- 24216413 TI - Hardwood tree growth after eight years on brown and gray mine soils in west virginia. AB - Surface coal mining in Appalachia disturbs hundreds of hectares of land every year with the removal of valuable and ecologically diverse eastern deciduous forests. After the passage of the Surface Mining Control and Reclamation Act in 1977, coal mine operators began planting a variety of grasses and legumes as a fast and economical way to reestablish a permanent vegetative cover to meet erosion and site stabilization requirements. However, soil compaction and competitive forage species have arrested the recolonization of native hardwood tree species on these reclaimed sites. Three 2.8-ha demonstration plots were established at Catenary Coal's Samples Mine in Kanawha County, West Virginia, of weathered brown sandstone and unweathered gray sandstone. Half of each plot was compacted. Each plot was hydroseeded with a low-competition herbaceous cover and planted with 11 hardwood tree species. After eight growing seasons, average tree volume index was nearly 10 times greater for trees grown in the brown sandstone treatments, 3853 cm, compared with 407 cm in gray sandstone. Trees growing on compacted treatments had a lower mean volume index, 2281 cm, than trees growing on uncompacted treatments, 3899 cm. Average pH of brown sandstone was 5.2 to 5.7, while gray sandstone was 7.9. The gray sandstone had much lower fine soil fraction (<2-mm) content (40%) than brown sandstone (70%), which influenced nutrient- and water-holding capacity. Brown sandstone showed significantly greater tree growth and survival and at this stage is a more suitable topsoil substitute than gray sandstone on this site. PMID- 24216414 TI - Hardwood tree growth on amended mine soils in west virginia. AB - Each year surface mining in Appalachia disrupts large areas of forested land. The Surface Mining Control and Reclamation Act requires coal mine operators to establish a permanent vegetative cover after mining, and current practice emphasizes soil compaction and planting of competitive forage grasses to stabilize the site and control erosion. These practices hinder recolonization of native hardwood trees on these reclaimed sites. Recently reclamation scientists and regulators have encouraged re-establishment of hardwood forests on surface mined land through careful selection and placement of rooting media and proper selection and planting of herbaceous and tree species. To evaluate the effect of rooting media and soil amendments, a 2.8-ha experimental plot was established, with half of the plot being constructed of weathered brown sandstone and half constructed of unweathered gray sandstone. Bark mulch was applied to an area covering both sandstone types, and the ends of the plot were hydroseeded with a tree-compatible herbaceous seed mix, resulting in eight soil treatments. Twelve hardwood tree species were planted, and soil chemical properties and tree growth were measured annually from 2007 to 2012. After six growing seasons, average tree volume index was higher for trees grown on brown sandstone (5333 cm) compared with gray sandstone (3031 cm). Trees planted in mulch outperformed trees on nonmulched treatments (volume index of 6187 cm vs. 4194 cm). Hydroseeding with a tree-compatible mix produced greater ground cover (35 vs. 15%) and resulted in greater tree volume index than nonhydroseed areas (5809 vs. 3403 cm). Soil chemical properties were improved by mulch and improved tree growth, especially on gray sandstone. The average pH of brown sandstone was 5.0 to 5.4, and gray sandstone averaged pH 6.9 to 7.7. The mulch treatment on gray sandstone resulted in tree growth similar to brown sandstone alone and with mulch. After 6 yr, tree growth on brown sandstone was about double the tree growth on gray sandstone, and mulch was a successful amendment to improve tree growth. PMID- 24216415 TI - Biochar and biosolids increase tree growth and improve soil quality for urban landscapes. AB - Urban soil quality is often degraded and a challenging substrate for trees. This study was conducted to assess the impacts of biochar (BC), biosolids (BS), wood chips (WC), compost (COM), aerated compost tea (ACT), and a nitrogen plus potassium fertilizer (NK) for improving three typical urban soils and tree sapling growth. Across the three soil types, the most significant changes in soil properties were observed with BS and BC. Biosolids decreased soil pH and increased available N, N mineralization, and microbial respiration. Biochar increased total organic C. Increases in microbial respiration were also observed with NK, COM, and WC in only the sand soil. Leachate concentrations of dissolved organic C were greater with BS and COM, but nitrate in leachates did not differ among the treatments. The greatest and most significant increases in and growth were found with BS and BC. Tree growth was modeled from plant-available N and microbial respiration. The N content in the treatments appeared to be a strong determinant of tree growth for all treatments except BC. Nitrogen fertilizer, COM, and WC are the most common urban soil amendments and mulches in use today. This study provides evidence that BS and BC are acceptable, and possibly preferred, alternatives for improving urban soil quality and tree growth. PMID- 24216416 TI - Life-cycle assessment of the beef cattle production system for the northern great plains, USA. AB - A life-cycle assessment (LCA) model was developed to estimate the environmental impacts associated with four different U.S. Northern Great Plains (NPG) beef production systems. The LCA model followed a "cradle-to-gate" approach and incorporated all major unit processes, including mineral supplement production. Four distinct operation scenarios were modeled based on production strategies common to the NGP, and a variety of impacts were determined. The scenarios include a normal operation, early weaning of the calf, fast-tack backgrounding, and grassfed. Enteric emissions and manure emissions and handling were consistently the largest contributors to the LCA impacts. There was little variability between production scenarios except for the grassfed, where the greenhouse gas (GHG) emissions were 37% higher due to a longer finishing time and lower finishing weight. However, reductions to GHG emissions (15-24%) were realized when soil organic carbon accrual was considered and may be a more realistic estimate for the NGP. Manure emissions and handing were primary contributors to potential eutrophication and acidification impacts. Mitigation strategies to reduce LCA impacts, including diet manipulation and management strategies (i.e., treatment of manure), were considered from a whole-systems perspective. Model results can be used for guidance by NGP producers, environmental practitioners, and policymakers. PMID- 24216417 TI - Indicate severe toxicity of highway runoff. AB - Road runoff is recognized as a substantial nonpoint source of contamination to the aquatic environment. Highway seasonal first flushes contain particularly high concentrations of pollutants. To fully account for the toxicity potential of the runoff, the cumulative effects of the pollutants should be assessed, ideally by biological analyses. Acute toxicity tests with were used to measure the toxicity of runoff from three major highway sections in Israel for 2 yr. Highway first flushes resulted in the mortality of all tested individuals within 24 to 48 h. A first flush collected from Highway 4 (traffic volume: 81,200 cars d) remained toxic even after dilution to <5% (48 h EC <5%). Synthetic solutions with metal concentrations corresponding to highways' first flushes revealed a synergistic adverse effect on survival and a potential additive effect of nonmetal pollutants in the runoff. Because daphnids and other invertebrates constitute the base of the aquatic food chain, detrimental effects of highway runoff may propagate to higher levels of biological organization. The observed high potential of environmental contamination warrants the control of highway runoff in proximity to natural watercourses. PMID- 24216418 TI - Selenium Adsorption onto Iron Oxide Layers beneath Coal-Mine Overburden Spoil. AB - A field experimental study to determine the feasibility of sequestering dissolved selenium (Se) leached from coal-mine waste rock used an iron (Fe)-oxide amendment obtained from a mine-drainage treatment wetland. Thirty lysimeters (4.9 * 7.3 m), each containing 57.7 t (1.2-1.8 m thickness) of mine-run carbonaceous shale overburden, were installed at the Hobet mine in southeastern West Virginia. The fine-grained Fe-oxide was determined to be primarily metal oxides (91.5% ferric and 4.37% aluminous), with minor (<3%) SO and Ca, perhaps as gypsum. The mineralogy of the Fe was goethite, although residual ferrihydrite may have been present. Various thicknesses of this amendment (0.0064, 0.057, 0.229, and 0.457 m, plus a zero-amendment control) were used, ranging from 0 to 2.2% weight percent of the spoil. The control and each treatment were replicated six times to estimate uncertainty due to compositional and hydrological variation. Infiltration of rainfall created leachate that drained to individual batch collection tanks that were sampled 46 times at approximately 2-wk intervals from 2010 to 2012. Basal Fe-oxide layers in the three highest amendment categories removed up to 76.1% selenium (in comparison to unamended piles) from leachate by adsorption. Only lysimeters with very thin Fe-oxide layers showed no significant reduction compared with unamended piles. Reproducibility of replicates was within acceptable limits for amended and unamended lysimeters. Results indicate that in situ amendment using Fe-oxide obtained from treatment of mine water can sequester Se by adsorption on surfaces of goethite and possibly also ferrihydrite. This process is demonstrated to substantially reduce dissolved Se in leachate and improve compliance with regulatory discharge limits. PMID- 24216419 TI - How paired is paired? Comparing nitrate concentrations in three iowa drainage districts. AB - Quantifying the effectiveness of perceived best management practices (BMPs) at the field and landscape-scale is difficult, so paired watershed studies are used to detect water quality improvements. We evaluated concentrations of NO-N discharged from three tiled Iowa watersheds during a 4-yr period to assess their suitability for a paired watershed approach. Our objectives were to evaluate similarities in physical characteristics, concentration patterns, and correlation among the three paired sites and perform a minimum detectable change (MDC) analysis on paired site configurations. The study results demonstrate that concentration variability within and between sample sites affected correlation among the paired basins, even though the physical characteristics of the basins are quite similar. Restricting comparisons to the active tile drainage period (March-July) improved correlations. The lack of a suitable correlation will impair the ability to detect changes expected to result from BMP implementation. The MDC for NO-N concentration change detection varied from 6.9 to 12.9% and averaged 8% for the best control-treatment pair. To ensure that conservation resources are being used effectively, implemented BMPs should focus on practices capable of achieving at least this magnitude of change. These practices may include reduced fertilizer applications, adoption of cover crops, and land use change. PMID- 24216420 TI - SPARROW Models Used to Understand Nutrient Sources in the Mississippi/Atchafalaya River Basin. AB - Nitrogen (N) and phosphorus (P) loading from the Mississippi/Atchafalaya River Basin (MARB) has been linked to hypoxia in the Gulf of Mexico. To describe where and from what sources those loads originate, SPAtially Referenced Regression On Watershed attributes (SPARROW) models were constructed for the MARB using geospatial datasets for 2002, including inputs from wastewater treatment plants (WWTPs), and calibration sites throughout the MARB. Previous studies found that highest N and P yields were from the north-central part of the MARB (Corn Belt). Based on the MARB SPARROW models, highest N yields were still from the Corn Belt but centered over Iowa and Indiana, and highest P yields were widely distributed throughout the center of the MARB. Similar to that found in other studies, agricultural inputs were found to be the largest N and P sources throughout most of the MARB: farm fertilizers were the largest N source, whereas farm fertilizers, manure, and urban inputs were dominant P sources. The MARB models enable individual N and P sources to be defined at scales ranging from SPARROW catchments (~50 km) to the entire area of the MARB. Inputs of P from WWTPs and urban areas were more important than found in most other studies. Information from this study will help to reduce nutrient loading from the MARB by providing managers with a description of where each of the sources of N and P are most important, thus providing a basis for prioritizing management actions and ultimately reducing the extent of Gulf hypoxia. PMID- 24216421 TI - Abiotic reduction of 1,3-dinitrobenzene by aqueous dissolved extracellular polymeric substances produced by microorganisms. AB - Extracellular polymeric substances (EPS) secreted by microorganisms make up an important constituent of labile and semilabile dissolved organic matter in surface water. There are no literature reports on the capability of EPS to reduce organic pollutants. This study demonstrated that EPS could effectively reduce a probe nitroaromatic compound, 1,3-dinitrobenzene. In aqueous dissolved EPS (60.3 mg L, produced by ), 1,3-dinitrobenzene (2.1 mg L) was completely reduced to 3 hydroxylaminonitrobenzene and 3-nitroaniline within 45 h (30 degrees C; pH 5.6). The reduction of 1,3-dinitrobenzene followed pseudo-first-order kinetics (rate constant [], 4.3 * 10 h). Fourier transform infrared and C nuclear magnetic resonance spectroscopy analyses combined with Tollen's test suggest that hemiacetal of rhamnose structures and reduced phenolic groups in EPS acted as the reducing agents. The abiotic nature of the reaction was further verified by the electrochemical cell experiments where the measured quantity of electron transfer through the external circuit was in principle equal to the stoichiometric demand to reduce 1,3-dinitrobenzene. The reduction of 1,3-dinitrobenzene by EPS was markedly facilitated by the addition of model juglone (1 mg L), confirming the "electron shuttle" role of quinoid-like structures in EPS. Moreover, the reaction was dependent on the pH and the concentration of metal ions (Na, Zn, or Cu). Additional tests confirmed the universality of 1,3-dinitrobenzene reduction by other sources of EPS (, , , and natural freshwater biofilm). The results indicate that EPS are reductively labile and can contribute to the natural attenuation and remediation of environmental organic contaminants. PMID- 24216422 TI - Effectiveness of Aluminum-based Drinking Water Treatment Residuals as a Novel Sorbent to Remove Tetracyclines from Aqueous Medium. AB - Low levels of various veterinary antibiotics (VAs) have been found in water resources across the United States as a result of nonpoint-source pollution. As the first phase of developing a potential green sorbent for tetracycline (TTC) and oxytetracycline (OTC), we examined the effects of solution chemistry, pH, ionic strength (IS), sorbate:sorbent ratio (SSR), and reaction time on TTC and OTC sorption by a waste byproduct of the drinking-water treatment process, namely, Al-based drinking-water treatment residuals (Al-WTR). The sorption of TTC and OTC on Al-WTR increased with increasing pH up to pH 7 and decreased in the pH range of 8 to 11. A concentration of 20 g L was deemed as optimum SSR, where more than 95% of the initially added TTC and OTC were sorbed and equilibrium was reached in 2 h. A pseudo-second-order model ( = 0.99) was used for Al-WTR sorption for TTC and OTC. The data best fit the linearized form of the Freundlich isotherm ( = 0.98). No significant effect ( > 0.05) of IS on sorption of TTC and OTC was observed between 0.05 and 0.5 mmol L. However, at higher initial concentrations (>1 mmol L), IS dependence on TTC and OTC sorption was observed. Surface complexation modeling and Fourier transform infrared spectroscopy analysis indicated the possibility of TTC and OTC forming a mononuclear monodentate surface complex through strong innersphere-type bonds on Al-WTR. The results show promising potential of Al-WTR for use as a "green" and cost effective sorbent to immobilize and stabilize TTC in soils and waters. PMID- 24216423 TI - Sorption/Desorption of lincomycin from three arid-region soils. AB - The antibiotic lincomycin is commonly found in treated municipal waste water and in waste from swine and poultry production. Environmental disposal of these wastes has the potential to introduce a significant mass of lincomycin into the ecosystem. In the present study, a series of sorption and desorption experiments were conducted to determine the potential mobility of lincomycin in soils from arid environments. Sorption and desorption isotherms were obtained for lincomycin using three different soils. Isotherms were fit to the Freundlich equation. Adsorption of lincomycin was found to have a of 11.98 for a biosolid-treated soil (1.58% OC) and a of 210.15 for a similar unamended soil (1.42% OC). It was also found that for a low-organic-content soil the was 5.09. The differences in adsorption can be related to the soil pH and the pKa of lincomycin (7.5-7.8). When the soil solution pH is below the pKa, the cationic species of lincomycin dominates, resulting in increased water solubility. Interaction with the cation exchange complex is minimal due to a high solution cation concentration (Ca and Na). Desorption isotherms also indicate that when the solution pH is lower than the pKa, retention of lincomycin is reduced. Our results indicate that the mobility of lincomycin in these arid region soils is dependent on soil pH. PMID- 24216424 TI - Quantifying climate and management effects on regional crop yield and nitrogen leaching in the north china plain. AB - Better water and nitrogen (N) management requires better understanding of soil water and N balances and their effects on crop yield under various climate and soil conditions. In this study, the calibrated Root Zone Water Quality Model (RZWQM2) was used to assess crop yield and N leaching under current and alternative management practices in a double-cropped wheat ( L.) and maize ( L.) system under long-term weather conditions (1970-2009) for dominant soil types at 15 locations in the North China Plain. The results provided quantitative long term variation of deep seepage and N leaching at these locations, which strengthened the existing qualitative knowledge for site-specific management of water and N. In general, the current management practices showed high residual soil N and N leaching in the region, with the amounts varying between crops and from location to location and from year to year. Seasonal rainfall explained 39 to 84% of the variability in N leaching (1970-2009) in maize across locations, while for wheat, its relationship with N leaching was significant ( < 0.01) only at five locations. When N and/or irrigation inputs were reduced to 40 to 80% of their current levels, N leaching generally responded more to N rate than to irrigation, while the reverse was true for crop yield at most locations. Matching N input with crop requirements under limited water conditions helped achieve lower N leaching without considerable soil N accumulation. Based on the long-term simulation results and water resources availability in the region, it is recommended to irrigate at 60 to 80% of the current water levels and fertilize only at 40 to 60% of the current N rate to minimizing N leaching without compromising crop yield. PMID- 24216425 TI - Sediment and Phosphorus Accumulation Dynamics behind Newly Installed Low-Grade Weirs in Agricultural Drainage Ditches. AB - Low-grade weirs are controlled surface drainage management structures that are being advocated for improving water quality of downstream ecosystems within agricultural landscapes. Low-grade weirs are small controlled drainage structures that are placed in series in an agricultural drainage ditch to create biogeochemical conditions for enhanced nutrient retention but also to slow runoff velocities and encourage sedimentation. This study evaluated eight low-grade weirs for sediment and P accumulation in agricultural drainage ditches 1 yr after installation. On average, sediment (weir: 54 +/- 25cm; reference: 13 +/- 7 cm; <= 0.001) and water (weir: 9 +/- 7cm; reference: 1.16 +/- 2 cm; <= 0.05) depth was greater upstream of weirs when compared within ditch references sites. There were no significant differences in total P concentrations of sediments or between any P fractions between 1-yr-old weirs and their respective references. Bioavailability ratios of P (i.e., the ratio of potentially bioavailable to nonbioavailable P fractions) were also found to be similar between weir and reference sites. Based on these results, weirs increase the hydrological capacity of drainage ditches and significantly retain more sediment and P within the drainage ditch within 1 yr of construction. Future research will examine temporal changes in weir sediments and associated P concentrations to aid our understanding of how maintenance of weirs should occur to maximize physical and chemical characteristics for greatest sediment and P retention. PMID- 24216426 TI - Classification of Nitrate Polluting Activities through Clustering of Isotope Mixing Model Outputs. AB - Apportionment of nitrate (NO) sources in surface water and classification of monitoring locations according to NO polluting activities may help implementation of water quality control measures. In this study, we (i) evaluated a Bayesian isotopic mixing model (stable isotope analysis in R [SIAR]) for NO source apportionment using 2 yr of deltaN-NO and deltaO-NO data from 29 locations within river basins in Flanders (Belgium) and five expert-defined NO polluting activities, (ii) used the NO source contributions as input to an unsupervised learning algorithm (k-means clustering) to reclassify sampling locations into NO polluting activities, and (iii) assessed if a decision tree model of physicochemical data could retrieve the isotope-based and expert-defined classifications. Based on the SIAR and deltaB results, manure/sewage was identified as a major NO source, whereas soil N, fertilizer NO, and NH in fertilizer and rain were intermediate sources and NO in precipitation was a minor source. The k-means clustering algorithm allowed classification of NO polluting activities that corresponded well to the expert-defined classifications. A decision tree model of physicochemical parameters allowed us to correctly classify 50 to 100% of the sampling locations as compared with the k-means clustering approach. We suggest that NO polluting activities can be identified via clustering of NO source contributions from samples representing an entire river basin. Classification of future monitoring locations into these classes could use decision tree models based on physicochemical data. The latter approach holds a substantial degree of uncertainty but provides more inherent information for dedicated abatement strategies than monitoring of NO concentrations alone. PMID- 24216427 TI - Extent, characterization, and sources of soil lead contamination in small-urban residential neighborhoods. AB - We present high spatial-resolution mapping of soil lead (Pb) concentrations in a small-urban residential setting. X-ray fluorescence was used to measure soil Pb at170 properties in the City Park neighborhood of Appleton, Wisconsin. Greater than two-thirds of soil samples collected from drip lines contained more than 400 MUg g of Pb, and one third exceeded 1200 MUg g. Soils adjacent to homes built before 1960 contained significantly higher Pb levels than those near younger homes. Three front yard locations (drip line, mid-yard, and terrace) were sampled at 71 properties. A general decline in soil Pb with increasing distance from the house was observed. Detailed sampling of individual homes within a single residential block revealed Pb-contaminated soil radiating outward from homes in all directions, creating a "bulls-eye" pattern. Approximately 40% of yard space exceeded concentrations of 400 MUg g. These patterns of contamination are consistent with Pb paint as the main contributor of Pb to soil. This has important implications because spatial distribution of Pb contamination is fundamentally different if paint, rather than automobile exhaust, is the primary source. Selective sequential extraction analyses suggest that roughly half of the soil Pb resides in chemically reactive and bioavailable phases. The extent and persistence of soil Pb, the resurgence of home gardening, and the serious health consequences of Pb ingestion argue for attention to this problem, not just in dense urban centers but also in smaller urban settings across the country. PMID- 24216428 TI - Denitrification and potential nitrous oxide and carbon dioxide production in brownfield wetland soils. AB - Brownfields, previously developed sites that are derelict, vacant, or underused, are ubiquitous in urban areas. Wetlands on brownfields often retain rain and stormwater longer than the surrounding landscape because they are low-lying; this increases the possibility for these areas to process waterborne contaminants from the urban environment. In the northeastern United States, atmospheric deposition of nitrate (NO) is high. Denitrification, a microbial process common in wetlands, is a means of removing excess NO. Nitrogen gas is the desired end product of denitrification, but incomplete denitrification results in the production of NO, a greenhouse gas. The goal of this study was to investigate the potential of brownfield wetlands to serve as sinks for inorganic nitrogen and sources of greenhouse gases. We examined limitations to denitrification and NO production in brownfield wetland soils in New Jersey. Soil C:N ratios were high (18-40) and intact core denitrification (-0.78 to 11.6 MUg NO-N kg dry soil d) and N mineralization (0.11-2.97 mg N kg dry soil d) were low for all sites. However, soil NO increased during dry periods. Nitrate additions to soil slurries increased denitrification rates, whereas labile C additions did not, indicating that soil denitrifiers were nitrogen limited. Incubations indicated that the end product of denitrification was primarily NO and not N. These results indicate that brownfield wetlands can develop significant denitrification capacity, potentially causing NO limitation. They might be significant sinks for atmospheric NO but may also become a significant source of NO if NO deposition were to increase. PMID- 24216429 TI - Using the mehlich-3 soil test as an inexpensive screening tool to estimate total and bioaccessible lead in urban soils. AB - In cities nationwide, urban agriculture has been put on hold because of the high costs of soil testing for historical contaminants such as lead (Pb). The Mehlich 3 soil test is commonly used to determine plant available nutrients, is inexpensive, and has the potential to estimate trace metals in urban soil. The objectives of this study are to evaluate the ability of the Mehlich-3 to estimate total Pb and bioaccessible Pb in vacant residential lots. Total and bioaccessible Pb were determined in 68 vacant residential lots in Cleveland, OH, using standard USEPA Method 3051A and the Relative Bioaccessibility Leaching Procedure (RBALP), respectively. The Mehlich-3 soil test was used to determine extractable Pb, and the results show Mehlich-3 was strongly correlated with total and bioaccessible Pb. The Mehlich-3 soil test could be used as a screening tool to not only estimate total Pb (slope 1.73, = 0.970) but also to estimate bioaccessible Pb when using RBALP at pH 1.5 (slope 1.67, = 0.975) and RBALP at pH 2.5 (slope 1.15, = 0.938). Additional samples were collected from the Thackeray Avenue site in Cleveland, OH, to demonstrate the ability of the Mehlich-3 soil test to screen soil for Pb. The results from the Thackeray site show good agreement between Mehlich-3 and the standard USEPA methods. A screening protocol for urban vacant residential lots using the Mehlich-3 soil test is proposed. PMID- 24216430 TI - Trace metal contamination influenced by land use, soil age, and organic matter in montreal tree pit soil. AB - The short life span of many street trees in the Montreal downtown area may be due in part to higher than standard concentrations of trace metals in the tree pit soils. The effects of land use, soil organic matter, and time since tree planting in a given tree pit (soil age) were studied with respect to the total concentration of trace metals (Cr, Ni, Cu, Zn, Cd, and Pb) in soil collected from tree pits on commercial and residential streets. Contingency table analysis and multiple linear regression were applied to study how these variables were related to the total concentrations of trace metals in soil. Other variables, such as pH, street width, distance of the tree pit from the curb, and tree pit volume, were also used as input to statistical analysis to increase the analysis' explanatory power. Significantly higher concentrations of Cu, Cd, Zn, and Pb were observed in soils from commercial streets, possibly as a result of heavier traffic as compared with residential streets. Soil organic matter was positively correlated with the concentrations of Cu and Pb, probably due to the ability of organic matter to retain these trace metals. Nickel, Cu, Zn, Cd, and Pb were positively correlated with the soil age presumably because trace metals accumulate in the tree pit soil over time. This knowledge can be helpful in providing soil quality standards aimed at improving the longevity of downtown street trees. PMID- 24216431 TI - Nutrient leaching from mixed-species Florida residential landscapes. AB - Nutrient losses from residential lawns and landscapes can negatively impact water quality. Information about nutrient leaching from established residential landscapes containing a mixture of woody ornamental plants and turfgrass is limited. The objective of our study was to determine the effect of vegetation cover (turfgrass vs. woody ornamental) on nutrient leaching from established landscapes. Nine drainage lysimeters were planted with three vegetation treatments with the following coverage: (i) 60% turfgrass, 40% ornamental; (ii) 75% turfgrass, 25% ornamental; and (iii) 90% turfgrass, 10% ornamental. Daily leachate samples were collected and combined to produce weekly flow-weighted samples for 1 yr. Leachate samples were analyzed for total Kjeldahl N (TKN), nitrate (+ nitrite)-N (NO), ammonium-N (NH-N), and dissolved reactive phosphorus (DRP). The ratio of actual evapotranspiration (ET) to reference evapotranspiration (ET) was similar among treatments. However, drainage from the 90% turfgrass lysimeters was periodically higher than from the 60 and/or 75% turfgrass treatments. In most cases, leachate N and P concentrations and loads followed the same trend as drainage. The addition of shrubs in the 60 and 75% turfgrass treatments reduced leachate when rainfall was low and irrigation was the main water input. We suggest that established woody ornamental plants are more effective at absorbing water and nutrients than turfgrass due, in part, to increased root biomass and deeper rooting of established woody plants, which allows for more efficient uptake of soil water and nutrients. The use of woody plants in residential landscapes can reduce nutrient leaching in urban areas. PMID- 24216432 TI - Effectiveness of biochar for sorption of ammonium and phosphate from dairy effluent. AB - The use of biochar for recovery of excess nutrients in dairy manure effluent and the use of nutrient-enriched biochar as soil amendment can offer a robust solution for multiple environmental issues. In this study we determined the capacity of biochar, produced by pyrolyzing mixed hardwood feedstock at 300 degrees C, to adsorb and retain or release two major nutrient ions: ammonium (NH) and phosphate (PO). We conducted the experiment using a range of nutrient concentrations that represent those commonly observed in dairy manure effluent (0 50 mg L for PO and 0-1000 mg L for NH). Up to 5.3 mg g NH and 0.24 mg g PO was adsorbed from manure by biochar (18 and 50% of total amount in the manure slurry, respectively). During the desorption phase of the experiment, biochar retained 78 to 91% of the sorbed NH and 60% of the sorbed PO at reaction times <24 h. Our findings confirm that biochar can be used for recovering excess nitrogen and phosphorus from agricultural water, such as dairy manure effluent. PMID- 24216433 TI - Water and methyl isothiocyanate distribution in soil after drip fumigation. AB - Methyl isothiocyanate (MITC) generators, such as metam sodium (Met-Na), are used for soil fumigation of agricultural land. The ban on the fumigant methyl bromide has resulted in greater use of MITC generators. To understand the efficacy of MITC, it is necessary to assess its generation and disappearance kinetics when Met-Na is applied to soil. This study evaluated the movement of water and distribution and dissipation of MITC in soil after application of Met-Na through surface drip irrigation systems. The effects of varying water application volume (25, 50, and 75 mm) and rate (1.9, 5.0, and 7.5 L h m) were evaluated in a sandy loam soil. Good fumigant distribution within the sandy loam soil was observed under medium water application amount (50 mm) with slow to intermediate drip application rates (1.9-5.0 L h m). Low water application amount (25 mm) or high application rate (7.5 L h m) did not provide adequate MITC distribution throughout the soil bed width and rooting depth. Dissipation patterns of MITC in soil in all water application amounts and rates followed first-order kinetics, with a rate constant of 0.025 +/- 0.004 h and a half-life of 27 +/- 3 h. Simulated water distribution through the soil profile using HYDRUS 2D/3D fitted measured field data well, and the model accurately simulated MITC fumigant distribution in the soil. PMID- 24216434 TI - Properties and degradability of hydrothermal carbonization products. AB - Biomass carbonized via hydrothermal carbonization (HTC) yields a liquid and a carbon (C)-rich solid called hydrochar. In soil, hydrochars may act as fertilizers and promote C sequestration. We assumed that the chemical composition of the raw material (woodchips, straw, grass cuttings, or digestate) determines the properties of the liquid and solid HTC products, including their degradability. Additionally, we investigated whether easily mineralizable organic components adsorbed on the hydrochar surface influence the degradability of the hydrochars and could be removed by repetitive washing. Carbon mineralization was measured as CO production over 30 d in aerobic incubation experiments with loamy sand. Chemical analysis revealed that most nutrients were preferably enriched in the liquid phase. The C mineralization of hydrochars from woodchips (2% of total C added), straw (3%), grass (6%), and digestate (14%) were dependent on the raw material carbonized and were significantly lower (by 60-92%; < 0.05) than the mineralization of the corresponding raw materials. Washing of the hydrochars significantly decreased mineralization of digestate-hydrochar (up to 40%) but had no effect on mineralization rates of the other three hydrochars. Variations in C mineralization between different hydrochars could be explained by multiple factors, including differences in the O/C-H/C ratios, C/N ratios, lignin content, amount of oxygen-containing functional groups, and pH. In contrast to the solids, the liquid products were highly degradable, with 61 to 89% of their dissolved organic C being mineralized within 30 d. The liquids may be treated aerobically (e.g., for nutrient recovery). PMID- 24216435 TI - Nutrient loss in leachate and surface runoff from surface-broadcast and subsurface-banded broiler litter. AB - Subsurface band application of poultry litter has been shown to reduce the transport of nutrients from fields in surface runoff compared with conventional surface broadcast application. Little research has been conducted to determine the effects of surface broadcast application and subsurface banding of litter on nutrients in leachate. Therefore, a field experiment was conducted to determine the effects of subsurface band application and surface broadcast application of poultry litter on nutrient losses in leachate. Zero-tension pan and passive capillary fiberglass wick lysimeters were installed in situ 50 cm beneath the soil surface of an established tall fescue ( Schreb.) pasture on a sandy loam soil. The treatments were surface broadcast and subsurface-banded poultry litter at 5 Mg ha and an unfertilized control. Results of the rainfall simulations showed that the concentrations of PO-P and total phosphorus (TP) in leachate were reduced by 96 and 37%, respectively, in subsurface-banded litter treatment compared with the surface-applied litter treatment. There was no significant difference in PO-P concentration between control and subsurface-banded litter treatment in leachate. The trend in the loading of nutrients in leachate was similar to the trend in concentration. Concentration and loading of the nutrients (TP, PO-P, NH-N, and NO-N) in runoff from the subsurface-banded treatment were significantly less than for the surface-applied treatment and were similar to those from control plots. These results show that, compared with conventional surface broadcast application of litter, subsurface band application of litter can greatly reduce loss of P in surface runoff and leachate. PMID- 24216436 TI - The characterization of microorganisms in dairy wastewater storage ponds. AB - Dairy wastewaters from storage ponds are commonly land applied to irrigate forage crops. Given that diverse microbial populations are associated with cattle feces, the objective of this study was to use a culture-independent approach to characterize bacteria and archaea in dairy wastewaters. Using domain-specific primers, a region of the 16S rRNA gene was amplified from pooled DNA extracts from 30 dairy wastewaters and subsequently used to create a clone library. A total of 152 bacterial clones were examined and sequence matches were affiliated with the following groups: Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Synergistetes. Firmicutes was identified as the largest phylum, representing up to 69% of the clone sequences. Of 167 clones representing Archaea, seven genera were found to be closely related (91-100% sequence similarity) to isolates obtained from sediments and feces. Most of the putative sequence matches (98%) represented members from the class Methanomicrobia. With respect to the archaeal clones, only one of the putative sequence matches was affiliated with a methanogenic bacterium known to inhabit the rumen. PMID- 24216437 TI - Photochemical and bacterial transformations of disinfection by-product precursors in water. AB - In situ grab sampling from source waters and water extraction from source materials are common methods for determining disinfection by-product (DBP) formation potential (FP) of water samples or reactivity of dissolved organic matter (DOM) in forming DBPs during chlorination. However, DOM, as the main DBP precursor, collected using these techniques may not represent the DOM reacting with disinfectants due to biogeochemical alterations during water conveyance to drinking water treatment facilities. In this study, we exposed leachates from fresh litter and associated decomposed duff to natural sunlight or K-12 for 14 d and evaluated the changes, if any, on the propensity to form trihalomethane (THM), haloacetonitrile (HAN), and chloral hydrate (CHD) during chlorination. Sunlight treatment did not significantly change dissolved organic carbon (DOC) concentration but caused a 24 to 43% decrease in the specific ultraviolet absorbance (SUVA) at 254 nm, indicating that UV-active chromophores were transformed or degraded. There were significant increases ( < 0.05) in specific HAN formation potential (HAN-FP) and specific CHD formation potential (CHD-FP) (i.e., HAN and CHD formation potentials per unit carbon), but no change in specific THM formation potential (THM-FP) after sunlight exposure. In contrast, bacterial treatment did not show any significant effect on SUVA, specific chlorine demand, or any specific DBP-FPs, although bacterial colony counts suggested DOM in leachates was utilized for bacterial growth. Results of this study confirmed that the reactivity of DOM in forming DBPs could be different after biogeochemical processes compared with its source materials. For this study, photochemical reactions had a greater effect on DBP-FPs than did microbial degradation. PMID- 24216438 TI - Contamination in a brazilian river: a risk of exposure to untreated effluents. AB - Due to natural or anthropogenic activities, various chemical contaminants, such as toxic metals and organic compounds, enter water systems and can have multiple deleterious effects on many living organisms. The Todos os Santos River (TSR) in Brazil receives a high discharge of untreated effluents from various sources. The purpose of this study was to determine trace element concentrations in water samples from the TSR, evaluate the toxicological effects of these elements by using the (onion) test, and verify the physical-chemical parameters to establish the risk of exposure related to the contaminated river. The samples were taken in 2011 at six selected points (two upstream of an urban area, two in the urban area, and two downstream of the urban area) with physical-chemical parameters evaluated. The concentrations of Al (21.63-1688.84 MUg L), P (38.59-1760.87 MUg L), and Fe (478.9-8296.3 MUg L) were above the maximum levels permitted under Brazilian law (and the World Health Organization); little dissolved O was observed. Based on the test, genotoxic and mutagenic effects may occur in the river and could be due to anthropogenic increases in metal content. These important results have serious implications for the ecosystem as well as the health of the people who use the water. PMID- 24216439 TI - Groundwater science, 2nd edition. PMID- 24216440 TI - Update on new medicinal applications of gentamicin: evidence-based review. AB - Gentamicin (GM) was discovered in 1963 and was introduced into parenteral usage in 1971. Since then, GM has been widely used in medicinal applications. The Food and Drug Administration of the United States approved the routine prescription of GM to treat the following infectious disorders: infection due to Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Citrobacter spp., Enterobacteriaceae spp., Pseudomonas spp.; Staphylococcus infectious disease; bacterial meningitis; bacterial sepsis of newborns; bacterial septicemia; infection of the eye, bone, skin and/or subcutaneous tissue; infective endocarditis; peritoneal dialysis-associated peritonitis due to Pseudomonas and other gram-negative organisms; peritonitis due to gastrointestinal tract infections; respiratory tract infections; and urinary tract infectious disease. GM is an old antibiotic and is used widely beyond its FDA-labeled indications as follows: actinomycotic infection; Staphylococcus saprophyticus bacteremia with pyelonephritis; appendicitis; cystic fibrosis; diverticulitis; adjunct regimen for febrile neutropenia; female genital infection; uterine infection; postnatal infection; necrotizing enterocolitis in fetus or newborn; osteomyelitis; pelvic inflammatory disease; plague; gonorrhea; tularemia; prophylaxis of post cholecystectomy infection, transrectal prostate biopsy, and post-tympanostomy related infection; malignant otitis externa; and intratympanically or transtympanically for Meniere's disease. GM is also used in combination regimens, such as with beta-lactam antibiotics to treat mixed infection and with bacteriophage to treat Staphylococcus aureus infections. It is also added to medical materials, such as GM-loaded cement spacers for osteomyelitis and prosthetic joint-associated infections. Overall, there are many medicinal applications for GM. To reduce the development of GM-resistant bacteria and to maintain its effectiveness, GM should be used only to treat or prevent infections that are proven or strongly suspected as being caused by susceptible bacteria. In the future, we believe that GM will be used more widely in combination therapy and applied to medical materials for clinical applications. A definitive, appropriately powered study of this antibiotic and its clinical applications is now required, especially in terms of its effectiveness, safety, and cost. PMID- 24216441 TI - Gender and eye colour prediction discrepancies: A reply to criticisms. PMID- 24216442 TI - Wolbachia play an important role in affecting mtDNA variation of Tetranychus truncatus (Trombidiformes: Tetranychidae). AB - The prevalence of the endosymbiont Wolbachia and its effects on mitochondria variation were analyzed in seven natural populations of Tetranychus truncatus Ehara (Trombidiformes: Tetranychidae) in current study. Five Wolbachia strains (wtru1, wtru5, wtru7, wtru8, and wtru12) were detected based on the surface protein of Wolbachia (wsp) sequence data and the multiple locus sequences typing data, suggesting that multiple separate invasions have occurred. Part of mitochondrial cytochrome oxidase subunit I gene was sequenced from infected individuals revealing 10 different haplotypes. As predicted, the haplotype and nucleotide diversity were lower in infected individuals than that in uninfected individuals. Furthermore, phylogenetic and analysis of molecular variance analyses revealed that the distribution of mtDNA haplotypes is not associated with geography. Rather, it is strongly concordant with infection status. These data support the hypothesis that Wolbachia infection can affect the genetic structure and diversity of the host mites. PMID- 24216443 TI - How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE? PMID- 24216444 TI - Reply to: "Sorafenib efficacy for treatment of HCC recurrence after liver transplantation is an open issue". PMID- 24216445 TI - Sorafenib efficacy for treatment of HCC recurrence after liver transplantation is an open issue. PMID- 24216446 TI - Survival after sorafenib: expect the unexpected. PMID- 24216447 TI - Reply to: "How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?". PMID- 24216448 TI - Letter from the guest editor: Neuroimaging of the central skull base region. PMID- 24216449 TI - Practical anatomy of the central skull base region. AB - The central skull base region represents a complex intersection between the intracranial compartment, the osseous foundation of the skull base, the orbits, the paranasal sinuses, and the suprahyoid neck. A modern radiologic approach to this region should take into account the 3-dimensional complexity of the region as well as the cross-sectional anatomical detail available to today's radiologist. This analytical approach should permit identification of lesional anatomical subsites, establishment of lesional origins, and allow for an anatomy based differential diagnosis. In this article, we define a practical central skull base region that includes structures that directly affect neuroimaging of this dense landscape. By reframing the boundaries, the central skull base region becomes comprehensive, emphasizing the natural tendency for pathologic processes to involve contiguous anatomical subunits, and underscores the complexity and challenges of this region for neuroimaging specialists. PMID- 24216450 TI - Endocranial lesions. AB - Numerous intracranial soft tissue and vascular structures are intimately related to the endocranial surface of the central skull base, including the pituitary gland, the pachymeninges, and multiple cranial nerves. These structures can give rise to pathologies that create imaging abnormalities along the bony surface of the skull base or result in gross changes of the underlying bone: hyperostosis, scalloping, permeation, erosion, or destruction. Large lesions with frank invasion may be difficult to differentiate from intrinsic bone lesions. This article reviews a variety of endocranial lesions affecting the central skull base, including the giant or invasive pituitary macroadenoma and skull base meningioma, and highlights the imaging features for a practical approach to their diagnosis. PMID- 24216451 TI - Neuroimaging: intrinsic lesions of the central skull base region. AB - The sphenoid bone is the osseous foundation of the central skull base. The body of the sphenoid is cuboid in shape and its posterior margin is joined to the basilar occipital bone (basiocciput) via a synchondrosis to form the complete clivus. Traditionally, radiologic discussions of intrinsic disease of the central skull base emphasize marrow space-occupying lesions including metastatic disease, myeloma, and chordoma. Based on our practical experience and the anatomical boundaries of the central skull-based region put forth, we include lesions of the sphenoid sinus and petrous apex in our discussion. We describe lesions that might originate within, be confined to, or principally involve the skeletal foundation of the central skull base, including the pneumatized regions contained within. Intrinsic lesions affecting the central skull base are emphasized and the most important computed tomography and magnetic resonance imaging findings that allow for effective diagnosis, planning, and treatment are highlighted. PMID- 24216452 TI - Skull base lesions: extracranial origins. AB - A number of extracranial anatomical sites, including the nasopharynx, paranasal sinuses, and masticator space, may give rise to lesions involving the skull base. Implicit in the nature of an invasive lesion, the majority of these lesions are malignant. Accordingly, for optimal patient outcomes and treatment planning, it is imperative to include a search pattern for extracranial sites and to assess accurately the character and extent of these diverse lesions. Of particular importance to radiologists are lesions arising from each extracranial site, the search patterns, and relevant information important to convey to the referring clinician. PMID- 24216453 TI - Perineural tumor spread involving the central skull base region. AB - Perineural spread of tumor is defined as extension of the primary tumor along tissues of the neural sheath (epineurium and perineurium) of a named nerve. Given the density of cranial nerves in the central skull base region and their extracranial communications, perineural tumor spread from a variety of sources can affect the central skull base region. Common malignancies with perineural tumor spread to central skull base include mucosal squamous cell carcinoma, adenoid cystic carcinoma, and cutaneous malignancies including melanoma. The presence and extent of tumor spread influence selection of treatment and prognosis. Appropriate imaging and interpretation, therefore, play a crucial role in detection and management of perineural tumor spread in the central skull base region. PMID- 24216454 TI - Vascular lesions of the central skull base region. AB - The arterial and venous structures of the central skull base region form complex anatomical relationships with each other and with adjacent osseous and neural structures. Vascular structures including the cavernous sinuses and internal carotid arteries can be displaced, encased, or invaded by neoplastic, inflammatory, or infectious lesions of the central skull base. Consequently, the vascular structures have a unique role in determining the imaging appearance, clinical significance, and therapeutic options of lesions occurring in the central skull base. This article briefly reviews the basic anatomy of the cavernous sinus and the relationship of the internal carotid artery to the cavernous sinus and central skull base. The major imaging features of some common vascular lesions, including skull base aneurysm, carotid-cavernous fistula, and cavernous sinus thrombosis are presented. PMID- 24216455 TI - Surgical approaches to central skull base and postsurgical imaging. AB - The close proximity to or intricate involvement of critical neurovascular structures in the central skull base region or both present unique surgical challenges. Varied surgical approaches may be used to remove tumors in this region, including open craniotomies and minimally invasive transnasal or transfacial endoscopic approaches. The ideal surgical technique is chosen based on multiple factors including the aggressiveness, histopathology, and location of the tumor with respect to regional neurovascular elements. Postsurgical image analysis of the central skull base requires an intimate understanding of preoperative and expected postoperative appearance in relation to the nature of the excision and surgical materials used. PMID- 24216456 TI - Assessing the influence of reactor system design criteria on the performance of model colon fermentation units. AB - Fermentation reactor systems are a key platform in studying intestinal microflora, specifically with respect to questions surrounding the effects of diet. In this study, we develop computational representations of colon fermentation reactor systems as a way to assess the influence of three design elements (number of reactors, emptying mechanism, and inclusion of microbial immobilization) on three performance measures (total biomass density, biomass composition, and fibre digestion efficiency) using a fractional-factorial experimental design. It was determined that the choice of emptying mechanism showed no effect on any of the performance measures. Additionally, it was determined that none of the design criteria had any measurable effect on reactor performance with respect to biomass composition. It is recommended that model fermentation systems used in the experimenting of dietary effects on intestinal biomass composition be streamlined to only include necessary system design complexities, as the measured performance is not benefited by the addition of microbial immobilization mechanisms or semi-continuous emptying scheme. Additionally, the added complexities significantly increase computational time during simulation experiments. It was also noted that the same factorial experiment could be directly adapted using in vitro colon fermentation systems. PMID- 24216457 TI - Isolation of a selenite-reducing and cadmium-resistant bacterium Pseudomonas sp. strain RB for microbial synthesis of CdSe nanoparticles. AB - Bacteria capable of synthesizing CdSe from selenite and cadmium ion were enriched from a soil sample. After repeated transfer of the soil-derived bacterial cultures to a new medium containing selenite and cadmium ion 42 times (during 360 days), an enrichment culture that can simultaneously remove selenite and cadmium ion (1 mM each) from the liquid phase was obtained. The culture's color became reddish-brown, indicating CdSe nanoparticle production, as confirmed by energy dispersive x-ray spectra (EDS). As a result of isolation operations, the bacterium that was the most responsible for synthesizing CdSe, named Pseudomonas sp. RB, was obtained. Transmission electron microscopy and EDS revealed that this strain accumulated nanoparticles (10-20 nm) consisting of selenium and cadmium inside and on the cells when cultivated in the same medium for the enrichment culture. This report is the first describing isolation of a selenite-reducing and cadmium-resistant bacterium. It is useful for CdSe nanoparticle synthesis in the simple one-vessel operation. PMID- 24216458 TI - Antioxidant properties of certain cereals as affected by food-grade bacteria fermentation. AB - The effects of fermentation by 2 food-grade bacteria (Bacillus subtilis and Lactobacillus plantarum) on antioxidant activities and the contents of phenolics and flavonoids in 4 cereals (specifically adlay, chestnut, lotus seed, and walnut) were determined and compared with those of their non-fermented counterparts. Results showed that antioxidant properties observed in the fermented and non-fermented cereals may vary with fermented starters. Fermentation was observed to increase the phenolic and flavonoid contents of the extracts. The effects on Bacillus-fermented cereals were stronger than on Lactobacillus-fermented cereals. In IC50 values (mg/mL) of extracts, the extracts of fermented cereal showed a stronger DPPH radical scavenging and ferric-reducing activities. Fermentation did not significantly alter the Fe(2+)-chelating activity in the extracts of chestnuts and lotus seeds. All cereals were shown significantly inhibited the production of LPS-induced intracellular reactive oxygen species (ROS) without creating obvious cytotoxic effects in the macrophage cells. These results suggest that the fermentation process enables cereal-based foods with enhanced antioxidant capacities to contribute to health and nutritional improvements in consumers. PMID- 24216459 TI - Single-cell-based breeding: Rational strategy for the establishment of cell lines from a single cell with the most favorable properties. AB - For efficient biomolecule production (e.g., antibodies, recombinant proteins), mammalian cells with high expression rates should be selected from cell libraries, propagated while maintaining a homogenous expression rate, and subsequently stabilized at their high expression rate. Clusters of isogenic cells (i.e., colonies) have been used for these processes. However, cellular heterogeneity makes it difficult to obtain cell lines with the highest expression rates by using single-colony-based breeding. Furthermore, even among the single cells in an isogenic cell population, the desired cell properties fluctuate stochastically during long-term culture. Therefore, although the molecular mechanisms underlying stochastic fluctuation are poorly understood, it is necessary to establish excellent cell lines in order to breed single cells to have higher expression, higher stability, and higher homogeneity while suppressing stochastic fluctuation (i.e., single-cell-based breeding). In this review, we describe various methods for manipulating single cells and facilitating single-cell analysis in order to better understand stochastic fluctuation. We demonstrated that single-cell-based breeding is practical and promising by using a high-throughput automated system to analyze and manipulate single cells. PMID- 24216460 TI - Hydrogen utilization rate: A crucial indicator for anaerobic digestion process evaluation and monitoring. AB - Hydrogenotrophic methanogens had been considered as key species for the anaerobic digestion (AD) of industrial wastewater and municipal sludge. However, how to evaluate the activity of the hydrogenotrophic methanogens was less studied. In this study, a volumetric device and a test procedure were developed for measuring the specific hydrogen utilization rate (HUR) of anaerobic sludge. Results showed that HUR values were highly influenced by sludge concentrations because of limitation on H2 mass transfer. The critical value of sludge concentration in the test bottle should not be higher than 1 gVSS/L. Under such condition, the kinetics of HUR would not be limited by H2 mass transfer and the maximal value of HUR could be obtained. Field survey confirmed that HUR exhibits a good relationship with specific methanogenic activity (SMA) and reactor performance. An anaerobic system with a relatively high HUR was found to be beneficial for maintaining H2 partial pressure in an appropriately low level. Moreover, such system was thermodynamically favourable for the syntrophic degradation of volatile fatty acids. As a crucial parameter of the anaerobic process, HUR could be used as a key indicator for evaluating and monitoring AD processes. PMID- 24216461 TI - Installation of orthogonality to the interface that assembles two modular domains in the Tetrahymena group I ribozyme. AB - Two modular elements (P5abc and DeltaP5) in the Tetrahymena group I ribozyme can be separated physically to generate a two-piece ribozyme derivative consisting of a separately prepared P5abc (P5 RNA) and the rest of the intron (DeltaP5 RNA). Molecular recognition in the interface assembling P5 RNA and DeltaP5 RNA is strong and specific, and the catalytic ability of the two-piece ribozyme is comparable to that of the parent unimolecular ribozyme. We designed alternative P14 (L5c-L2) interacting modules participating in the assembly of P5 and DeltaP5 and investigated their ability in the context of complex formation of the two piece ribozyme and in vivo splicing of the unimolecular intron ribozyme. Combined use of alternative P14 and L5b-P6 interacting modules provided robust orthogonality to the P5/DeltaP5 assembly interface of the bimolecular complex. PMID- 24216462 TI - Evolutionary analysis of the functional plasticity of Staphylococcus aureus C30 carotenoid synthase. AB - Most natural carotenoids have 40-carbon (C40) backbones, while some bacteria produce carotenoids with C30 backbones. Carotenoid backbone synthases, the enzyme that catalyze the first committed step in carotenoid biosynthesis, are known to be highly specific. Previously, using C30 backbone synthase (diapophytoene synthase, CrtM) from Staphylococcus aureus, we reported two size-shifting mutations, F26A and W38A, which confer C40 synthase activity at the cost of the original C30 synthase activity. In this study, we performed a directed evolution of the C40-specialist variant CrtMF26A in search of mutations that restore the original C30 synthase function. Examination of the resultant mutants, together with the site-directed mutagenesis study identified three new mutations (H12A, D27A and I240F) that affect the size specificity of this enzyme. After re defining the reading frame, we obtained CrtM variants that are highly active in C30 and C40 carotenoid synthesis. PMID- 24216463 TI - Acute skin graft-versus-host disease with molecular features mimicking herpes simplex virus-associated erythema multiforme: report of three cases. AB - BACKGROUND: Acute skin erythematous lesions that follow allogeneic hematopoietic stem cell transplantation (HSCT) and are histologically diagnosed as graft-versus host disease (GVHD) are often associated with reactivation of latent herpes simplex virus (HSV). OBJECTIVE: To further examine the relationship between reactivated HSV and GVHD development. METHODS: We present 3 patients with acute skin GVHD after allogeneic HSCT who were studied prospectively for expression of the HSV antigen Pol, which is involved in HSV-associated erythema multiforme. RESULTS: Pol was expressed in the GVHD lesions but not the pre-HSCT normal skin or peripheral blood mononuclear cells. Lesion severity correlated with the Pol levels but not the histopathologically defined GVHD grade. Lesion development was accompanied by increased numbers of Pol+ circulating/skin-infiltrating CD34+ stem cells and CD1a+ and other dermal dendritic cells. CONCLUSIONS: Subclinical HSV infection of circulating CD34+ cells can contribute to some post-HSCT skin lesions histologically diagnosed as GVHD, with potential preventive and therapeutic implications. PMID- 24216464 TI - 2013 JRR Terashima Award. PMID- 24216465 TI - Experimental study of nuclear fragmentation of 200 and 400 MeV/u (12)C ions in water for applications in particle therapy. AB - Carbon ion beams in the energy range of about 100-450 MeV/u offer excellent conditions for tumour therapy, in particular for the treatment of deep-seated radio-resistant tumours. Their depth-dose distribution is characterized by a low dose in the entrance channel, small lateral beam spread and an elevated biological effectiveness in the Bragg peak region. In comparison to protons the radiation field of heavier ions stopping in tissue is however more complex due to nuclear fragmentation reactions occurring along their stopping path. This results in an attenuation of the primary beam flux and a build-up of lower-Z fragments with longer ranges causing the characteristic dose tail beyond the Bragg peak. In the present work the characteristics of secondary charged particles at various depths of water were investigated experimentally using (12)C ion beams of 200 and 400 MeV/u delivered by the heavy-ion synchrotron SIS-18 at GSI Darmstadt. The nuclear charge Zf of secondary fragments was identified by combining energy loss and time-of-flight (TOF) measurements. Energy spectra and yields were recorded at lab angles of 0 degrees - 10 degrees and at seven different water depths corresponding to the entrance channel, the Bragg peak region and the tail of the Bragg curve. PMID- 24216466 TI - The Clinical Biomechanics Award 2013 -- presented by the International Society of Biomechanics: new observations on the morphology of the talar dome and its relationship to ankle kinematics. AB - BACKGROUND: Ankle passive kinematics is determined primarily by articular surface morphology and ligament constraints. Previous morphological studies concluded that the talar dome can be approximated by a truncated cone, whose apex is directed medially and whose major axis is the axis of rotation of the ankle. This and other functional morphology concepts were evaluated in this study whose goal was to describe and quantify the 3D morphology of the talus using 3D image-based bone models and engineering software tools. METHODS: CT data from 26 healthy adults were processed to produce 3D renderings of the talus and were followed by morphological measurements including the radii of curvature of circles fitted to the medial and lateral borders of the trochlea and radii of curvature of coronal sections. FINDINGS: The surfaces containing the medial and lateral borders of the trochlea are not parallel and the radius of curvature of the medial border is larger than the lateral border. In the coronal plane the trochlear surface was mostly concave. INTERPRETATION: The trochlear surface can be modeled as a skewed truncated conic saddle shape with its apex oriented laterally rather than medially as postulated by Inman. Such shape is compatible, as opposed to Inman's cone postulate, with the observed pronation/supination and provides stable congruency in movements of inversion/eversion. The results challenge the fundamental theories of functional morphology of the ankle and suggest that these new findings should be considered in future biomechanical research and in clinical applications such as design of total ankle replacements. PMID- 24216467 TI - Sessile serrated adenomas: an evidence-based guide to management. AB - The concept of serrated colorectal neoplasia and a serrated pathway to colorectal cancer (CRC) is relatively new and continuing to evolve, but it has become highly relevant to gastroenterologists, pathologist, and oncologists alike. Sessile serrated adenomas (SSA) are now thought to be the major precursor lesion of serrated pathway cancers, which represent up to one-third of all sporadic CRC cases. However, despite their increasingly recognized importance, relatively little is known about the epidemiology and natural history of SSAs, and the molecular and epigenetic aspects are incompletely understood. Endoscopists must be aware of the unique features of SSAs so that the practice of colonoscopic screening for CRC can include optimized detection, removal, and appropriate surveillance of SSAs and other serrated precursor lesions. In this review, we discuss the history, epidemiology, and pathologic aspects of SSAs, as well as a recommended management approach and a discussion of uncertainties and opportunities for future research. PMID- 24216468 TI - Reply: To PMID 23357488. PMID- 24216469 TI - Eosinophilic esophagitis--emerging epidemic or misdiagnosed malady? PMID- 24216471 TI - Endogenous cellulase enzymes in the stick insect (Phasmatodea) gut. AB - High cellulase (endo-beta-1,4-glucanase) activity was detected in the anterior midgut of the walking stick (Phasmatodea) Eurycantha calcarata. The enzyme was isolated and analyzed via mass spectrometry. RT-PCR revealed two endoglucanase genes, EcEG1 and EcEG2. Mascot analysis of the purified enzyme confirms it to be the product of gene EcEG1. Homologous cDNAs were also isolated from a distantly related species, Entoria okinawaensis, suggesting a general distribution of cellulase genes in phasmids. Phasmid cellulases showed high homology to endogenously-produced glycoside hydrolase family 9 (GH9) endoglucanases from insects, especially to those of termites, cockroaches, and crickets. The purified E. calcarata enzyme showed clear antigency against an anti-serum for termite GH9 cellulase, which, together with the sequence homology, further suggests an endogenous origin of the enzyme. This discovery suggests a possible nutritive value for cellulose in the leaf-feeding phasmids, unlike in herbivorous Lepidoptera. PMID- 24216470 TI - Silencing in Apolygus lucorum of the olfactory coreceptor Orco gene by RNA interference induces EAG response declining to two putative semiochemicals. AB - Apolygus lucorum (Meyer-Dur) (Hemiptera: Miridae) is an agronomically important pest that causes severe economic damage to the cotton, fruit, and vegetable industries. Similar to other insects, A. lucorum can perceive and discriminate olfactory cues. A highly conserved and broadly expressed olfactory coreceptor (Orco) is crucial for insect olfaction, and Orco orthologs have been identified in several insect species. In this study, a homology-based polymerase chain reaction (PCR) method was utilized to identify AlucOrco, an Orco ortholog essential for olfaction in A. lucorum. AlucOrco shares significant sequence homology with known Orco proteins in other insects. Quantitative real-time PCR (qRT-PCR) analysis revealed that AlucOrco was abundantly expressed in adult A. lucorum. AlucOrco expression level was the highest in the antennae; by contrast, AlucOrco showed negligible expression level in other tissues. We injected AlucOrco siRNA into the conjunctivum between the prothorax and mesothorax of A. lucorum and evaluated its expression 36 h after RNA interference. The results of qRT-PCR demonstrated that the level of mRNA expression was significantly reduced (>90%) in AlucOrco siRNA-treated A. lucorum than in water-injected and non injected controls. The electroantennogram responses of A. lucorum to two putative semiochemicals, trans-2-hexenal and trans-2-hexenyl butyrate, were also reduced significantly (~80%) in RNAi-treated A. lucorum than in the controls. These results suggest that AlucOrco is crucial in mediating odorant perception of A. lucorum, especially in perceiving trans-2-hexenal and trans-2-hexenyl butyrate. PMID- 24216472 TI - Love beyond borders. PMID- 24216473 TI - The real cost of caring or not caring. PMID- 24216474 TI - Tolfenamic acid induces apoptosis and growth inhibition in anaplastic thyroid cancer: Involvement of nonsteroidal anti-inflammatory drug-activated gene-1 expression and intracellular reactive oxygen species generation. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used for the treatment of inflammatory diseases. However, certain NSAIDs also have antitumor activities in various cancers, including head and neck cancer, through cyclooxygenase dependent or independent pathways. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a TGF-beta superfamily protein, is induced by NSAIDs and has been shown to be induced by several antitumorigenic compounds and to exhibit proapoptotic and antitumorigenic activities. In this report, we demonstrate for the first time that tolfenamic acid (TA) transcriptionally induced the expression of NAG-1 during TA-induced apoptosis of anaplastic thyroid cancer (ATC) cells. TA reduced the viability of ATC cells in a dose-dependent manner and induced apoptosis, findings that were coincident with NAG-1 expression. Overexpression of the NAG-1 gene using cDNA enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. Subsequently, we found that intracellular ROS generation plays an important role in activating the proapoptotic protein NAG-1. Then, we confirmed antitumorigenic effects of TA in a nude mouse orthotopic ATC model, and this result accompanied the augmentation of NAG-1 expression and ROS generation in tumor tissue. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression and ROS generation in in vitro and in vivo ATC models, providing a novel mechanistic explanation and indicating a potential chemotherapeutic approach for treatment of ATC. PMID- 24216475 TI - Gene expression profiling of candidate genes in peripheral blood mononuclear cells for predicting toxicity of diesel exhaust particles. AB - To validate gene expression profiling of peripheral blood mononuclear cells (PBMCs) as a surrogate for monitoring tissue expression, this study using RT-PCR based TaqMan low-density array (TLDA) was initiated to investigate similarities in the mRNA expression of target genes altered by exposure to diesel exhaust particles (DEPs) in freshly prepared PBMCs and in lungs. Adult Wistar rats were treated transtracheally with a single dose of 7.5 or 15 or 30mg/kg DEPs and sacrificed 24h later. Blood and lungs were immediately taken out and processed for RT-PCR. DEP treatment induced similar patterns of increase in the expression of polycyclic aromatic hydrocarbon-responsive cytochrome P450s, the phase II enzymes, and their associated transcription factors in both lungs and PBMCs, at all doses. Similar to that seen in lungs, a dose-dependent increase was observed in the expression of genes involved in inflammation, such as cytokines, chemokines, and adhesion molecules, in PBMCs. The expression of various genes involved in DNA repair and apoptosis was also increased in a dose-dependent manner in PBMCs and lungs. The present TLDA data indicating similarities in the responsiveness of candidate genes involved in the toxicity of DEPs between PBMCs and lungs after exposure to DEPs demonstrate that expression profiles of genes in PBMCs could be used as a surrogate for monitoring the acute toxicity of fine and ultrafine particulate matter present in vehicular emissions. PMID- 24216476 TI - A microenvironment-mediated c-Myc/miR-548m/HDAC6 amplification loop in non Hodgkin B cell lymphomas. AB - A dynamic interaction occurs between the lymphoma cell and its microenvironment, with each profoundly influencing the behavior of the other. Here, using a clonogenic coculture growth system and a xenograft mouse model, we demonstrated that adhesion of mantle cell lymphoma (MCL) and other non-Hodgkin lymphoma cells to lymphoma stromal cells confers drug resistance, clonogenicity, and induction of histone deacetylase 6 (HDAC6). Furthermore, stroma triggered a c-Myc/miR-548m feed-forward loop, linking sustained c-Myc activation, miR-548m downregulation, and subsequent HDAC6 upregulation and stroma-mediated cell survival and lymphoma progression in lymphoma cell lines, primary MCL and other B cell lymphoma cell lines. Treatment with an HDAC6-selective inhibitor alone or in synergy with a c Myc inhibitor enhanced cell death, abolished cell adhesion-mediated drug resistance, and suppressed clonogenicity and lymphoma growth ex vivo and in vivo. Together, these data suggest that the lymphoma-stroma interaction in the lymphoma microenvironment directly impacts the biology of lymphoma through genetic and epigenetic regulation, with HDAC6 and c-Myc as potential therapeutic targets. PMID- 24216477 TI - Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation. AB - The capacity of IL-10 and Tregs in the inflammatory tumor microenvironment to impair anticancer Th1 immunity makes them attractive targets for cancer immunotherapy. IL-10 and Tregs also suppress Th17 activity, which is associated with poor prognosis in several cancers. However, previous studies have overlooked their potential contribution to the regulation of pathogenic cancer-associated inflammation. In this study, we investigated the origin and function of IL-10 producing cells in the tumor microenvironment using transplantable tumor models in mice. The majority of tumor-associated IL-10 was produced by an activated Treg population. IL-10 production by Tregs was required to restrain Th17-type inflammation. Accumulation of activated IL-10+ Tregs in the tumor required type I IFN signaling but not inflammatory signaling pathways that depend on TLR adapter protein MyD88 or IL-12 family cytokines. IL-10 production limited Th17 cell numbers in both spleen and tumor. However, type I IFN was required to limit Th17 cells specifically in the tumor microenvironment, reflecting selective control of tumor-associated Tregs by type I IFN. Thus, the interplay of type I IFN, Tregs, and IL-10 is required to negatively regulate Th17 inflammation in the tumor microenvironment. Therapeutic interference of this network could therefore have the undesirable consequence of promoting Th17 inflammation and cancer growth. PMID- 24216478 TI - Peptidases released by necrotic cells control CD8+ T cell cross-priming. AB - Cross-priming of CD8+ T cells and generation of effector immune responses is pivotal for tumor immunity as well as for successful anticancer vaccination and therapy. Dead and dying cells produce signals that can influence Ag processing and presentation; however, there is conflicting evidence regarding the immunogenicity of necrotic cell death. We used a mouse model of sterile necrosis, in which mice were injected with sterile primary necrotic cells, to investigate a role of these cells in priming of CD8+ T cells. We discovered a molecular mechanism operating in Ag donor cells that regulates cross-priming of CD8+ T cells during primary sterile necrosis and thereby controls adaptive immune responses. We found that the cellular peptidases dipeptidyl peptidase 3 (DPP-3) and thimet oligopeptidase 1 (TOP-1), both of which are present in nonimmunogenic necrotic cells, eliminated proteasomal degradation products and blocked Ag cross presentation. While sterile necrotic tumor cells failed to induce CD8+ T cell responses, their nonimmunogenicity could be reversed in vitro and in vivo by inactivation of DPP-3 and TOP-1. These results indicate that control of cross priming and thereby immunogenicity of primary sterile necrosis relies on proteasome-dependent oligopeptide generation and functional status of peptidases in Ag donor cells. PMID- 24216479 TI - Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression. AB - RAS is the most frequently mutated oncogene in human cancers. Despite decades of effort, anti-RAS therapies have remained elusive. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins, but its potential as a target for cancer therapy has not been fully evaluated. We crossed a Pdx1-Cre;LSL-KrasG12D mouse, which is a model of pancreatic ductal adenocarcinoma (PDA), with a mouse harboring a floxed allele of Icmt. Surprisingly, we found that ICMT deficiency dramatically accelerated the development and progression of neoplasia. ICMT-deficient pancreatic ductal epithelial cells had a slight growth advantage and were resistant to premature senescence by a mechanism that involved suppression of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression. ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling. Silencing ICMT in human osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. Additionally, targeted silencing of Ste14, the Drosophila homolog of Icmt, resulted in defects in wing development, consistent with Notch loss of function. Our data suggest that ICMT behaves like a tumor suppressor in PDA because it is required for Notch1 signaling. PMID- 24216480 TI - Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. AB - Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family-based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR 513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA. PMID- 24216481 TI - Combined modulation of polycomb and trithorax genes rejuvenates beta cell replication. AB - Inadequate functional beta cell mass underlies both type 1 and type 2 diabetes. beta Cell growth and regeneration also decrease with age through mechanisms that are not fully understood. Age-dependent loss of enhancer of zeste homolog 2 (EZH2) prevents adult beta cell replication through derepression of the gene encoding cyclin-dependent kinase inhibitor 2a (INK4a). We investigated whether replenishing EZH2 could reverse the age-dependent increase of Ink4a transcription. We generated an inducible pancreatic beta cell-specific Ezh2 transgenic mouse model and showed that transgene expression of Ezh2 was sufficient to increase beta cell replication and regeneration in young adult mice. In mice older than 8 months, induction of Ezh2 was unable to repress Ink4a. Older mice had an enrichment of a trithorax group (TrxG) protein complex at the Ink4a locus. Knockdown of TrxG complex components, in conjunction with expression of Ezh2, resulted in Ink4a repression and increased replication of beta cells in aged mice. These results indicate that combined modulation of polycomb group proteins, such as EZH2, along with TrxG proteins to repress Ink4a can rejuvenate the replication capacity of aged beta cells. This study provides potential therapeutic targets for expansion of adult beta cell mass. PMID- 24216482 TI - Th9 cell development requires a BATF-regulated transcriptional network. AB - T helper 9 (Th9) cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor-like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation. PMID- 24216483 TI - Myelodysplastic syndromes are induced by histone methylation-altering ASXL1 mutations. AB - Recurrent mutations in the gene encoding additional sex combs-like 1 (ASXL1) are found in various hematologic malignancies and associated with poor prognosis. In particular, ASXL1 mutations are common in patients with hematologic malignancies associated with myelodysplasia, including myelodysplastic syndromes (MDSs), and chronic myelomonocytic leukemia. Although loss-of-function ASXL1 mutations promote myeloid transformation, a large subset of ASXL1 mutations is thought to result in stable truncation of ASXL1. Here we demonstrate that C-terminal truncating Asxl1 mutations (ASXL1-MTs) inhibited myeloid differentiation and induced MDS-like disease in mice. ASXL1-MT mice displayed features of human associated MDS, including multi-lineage myelodysplasia, pancytopenia, and occasional progression to overt leukemia. ASXL1-MT resulted in derepression of homeobox A9 (Hoxa9) and microRNA-125a (miR-125a) expression through inhibition of polycomb repressive complex 2-mediated (PRC2-mediated) methylation of histone H3K27. miR-125a reduced expression of C-type lectin domain family 5, member a (Clec5a), which is involved in myeloid differentiation. In addition, HOXA9 expression was high in MDS patients with ASXL1-MT, while CLEC5A expression was generally low. Thus, ASXL1-MT-induced MDS-like disease in mice is associated with derepression of Hoxa9 and miR-125a and with Clec5a dysregulation. Our data provide evidence for an axis of MDS pathogenesis that implicates both ASXL1 mutations and miR-125a as therapeutic targets in MDS. PMID- 24216485 TI - A historical perspective: stereotactic lesions for the treatment of epilepsy. AB - PURPOSE: Most deep brain stimulation targets for movement disorders were derived from effective ablative surgery targets. Similarly effective lesion targets for epilepsy control may help refine brain stimulation targeting for epilepsy. A literature review of past stereotactic lesions for epilepsy treatment was performed to provide historical context and possible anatomical guidance for current and future attempts at controlling epilepsy with electrical stimulation. This work was undertaken to provide insights for electrical stimulation targets in epilepsy treatment based on outcomes from previous ablative therapies. METHODS: A MEDLINE search was conducted for studies with the words "stereotactic surgery" and "epilepsy." Post-operative results for 619 patients with stereotactic brain lesions targeting various anatomical foci were standardized using a modified Engel scale (1 'free of seizures' to 3 'no significant improvement'). Each individual patient was entered into a database as a unique data point. RESULTS: There was a statistically significant difference in reported seizure control among the different procedures and seizure types. The procedures that produced the best seizure control outcomes were the hippocampectomy, pallido - amygdalotomy, and amygdalohippocampectomy. Simple partial motor and combined generalized tonic clonic with complex partial seizure types demonstrated the best outcomes following surgery; complex partial and generalized tonic had the worst outcomes. CONCLUSIONS: The results of this study demonstrate the location of brain lesions has a significant effect on seizure control. Thus, future research designed to optimize brain stimulation targets for epilepsy control may be informed by previous ablative outcomes. PMID- 24216484 TI - Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. AB - Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen related receptor alpha (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs. PMID- 24216486 TI - Enhancing children's vegetable consumption using vegetable-promoting picture books. The impact of interactive shared reading and character-product congruence. AB - The present study investigated whether and how a picture book promoting carrots can increase young children's carrot consumption. One hundred and four children (aged 4-6years) participated in shared reading sessions using the book on five consecutive days in school. These children were assigned randomly to one of four experimental conditions. In a 2*2 between-subjects design, the reading style and character in the book were manipulated. The reading style was either passive (listening to the story) or interactive (also answering questions about the story). The character in the book fitted either conceptually well with carrots (a rabbit) or not (a turtle). Compared to a baseline group of 56 children who were not exposed to the book, the children in the experimental groups consumed almost twice as much carrots (in proportion to other foods consumed), F(1,159)=7.08, p<.01. Results suggest that picture books are particularly effective when children are actively involved, answering questions about the story. Young children seem to enjoy this interactive shared reading style, triggering positive feelings that increase children's liking and consumption of the healthy food promoted in the book. PMID- 24216487 TI - "You must eat the salad because it is nutritious". Argumentative strategies adopted by parents and children in food-related discussions at mealtimes. AB - At mealtimes, the evaluation of the appropriate (or not appropriate) behavior concerning the food is often assumed as a topic of discourse. The aim of this study is to single out the argumentative strategies used by parents with their children and by children with their parents in order to convince the other party to eat or not to eat a certain food. Within a data corpus constituted by 30 video recorded meals of 10 middle to upper-middle-class Swiss and Italian families, we selected a corpus of 77 argumentative discussions between parents and children arisen around a food-related issue. Data are presented through discursive excerpts of argumentative discussions that were found within the data corpus and analyzed through the pragma-dialectical model of critical discussion. The results of this study show that the feeding practices in families with young children during mealtimes are argumentatively co-constructed by participants. In most cases parents put forward arguments based on the quality (e.g., very good, nutritious, salty, or not good) and quantity (e.g., too little, quite enough, or too much) of food to convince their children to eat. Similarly, children put forward arguments based on the quality and quantity of food to convince their parents to change their standpoint, although their view on the issue is the opposite of that of their parents. PMID- 24216488 TI - Behavioral response of grape root borer (Lepidoptera: Sesiidae) neonates to grape root volatiles. AB - Grape root borer, Vitacea polistiformis (Harris), is an oligophagous and potentially destructive pest of grape in commercial vineyards throughout much of the eastern United States. Larvae feed on vine roots, although little is known about their below-ground interactions with host plants. The behavioral response of groups of grape root borer neonates to stimuli from host and nonhost roots was evaluated in single and paired stimuli bioassays in which stimuli were presented in opposing wells attached to the bottom of petri dish arenas. Stimulus sources included root pieces and root headspace volatiles from 3309 and 420-A grape rootstocks (host) and apple (nonhost) and ethanol-based extracts of 3309 and 420 A roots. In single stimulus assays, significantly more larvae were recovered from wells containing grape roots, apple roots, grape extracts, and grape root volatiles than from control wells, but there was no significant response to volatiles collected from the headspace of apple roots. In paired stimuli assays, significantly more larvae were recovered from wells containing grape than apple roots. There was no difference in larval distribution between wells when 420-A and 3309 roots were presented simultaneously, although a significantly greater response to 3309 than 420-A root extract was recorded. When soil was added to the assays, significantly more larvae were recovered from wells containing grape roots than from those containing only soil, but this response was not detected in assays using buried apple roots. These results are discussed in relation to the plant-insect interactions between grape root borer larvae and their Vitaceae hosts. PMID- 24216489 TI - Molecular characterization of canine coronavirus strains circulating in Brazil. AB - To characterize canine coronavirus (CCoV) circulating in diarrheic puppies in Brazil, 250 fecal samples collected between 2006 and 2012 were tested. By using RT-PCR to partially amplify the M gene, CCoV RNA was detected in 30 samples. Sequence analysis of the M protein grouped eight strains with CCoV-I and another 19 with CCoV-II prototypes. To genotype/subtype the CCoV strains and assess the occurrence of single or multiple CCoV infections, RT-PCR of the S gene was performed, and 25/30 CCoV-positive strains amplified with one or two primer pairs. For 17/25 samples, single infections were detected as follows: six CCoV-I, nine CCoV-IIa and two CCoV-IIb. Eight samples were positive for more than one genotype/subtype as follows: seven CCoV-I/IIa and one CCoV-I/IIb. Sequence analysis revealed that the CCoV-I and IIa strains shared high genetic similarity to each other and to the prototypes. The Brazilian strains of CCoV-IIb displayed an aminoacid insertion that was also described in CCoV-IIb-UCD-1 and TGEV strains. Among the 25 CCoV-positive puppies, five had a fatal outcome, all but one of which were cases of mixed infection. The current study is the first reported molecular characterization of CCoV-I, IIa and IIb strains in Brazil. PMID- 24216490 TI - Decreased surgical time with a vessel sealing device versus a surgical stapler in performance of canine splenectomy. AB - The purpose of this retrospective study of 72 dogs was to compare a vessel sealing device with a surgical stapling device for performance of splenectomy. The results of this study demonstrate a statistically significant shorter surgical time for splenectomy, without an adverse effect on outcomes, performed in dogs with the vessel sealing device (mean time, 58.4 min +/- 3.3 min; median time, 60 min; range, 22-131 min) compared with a traditional stapling device (mean time, 66.9 min +/- 2.4 min; median time, 66 min; range, 40-100 min). No other significant differences were found between the two groups of patients. PMID- 24216491 TI - A retrospective study of feline gastric lymphoma in 16 chemotherapy-treated cats. AB - The purposes of this study were to describe cases of feline gastric lymphoma with regards to signalment, clinical presentation, laboratory and ancillary study findings, response to therapy, and outcomes and to identify prognostic variables. Sixteen cats with stage I and II gastric lymphoma treated with chemotherapy were included in this study. Seventy-five percent of cats experienced remission. Overall, first remission duration was 108 days. Response to treatment was prognostic as in other types of feline lymphoma. Cats with a complete remission (CR) had longer survival times compared with cats with a partial remission (PR). Sex and treatment with a rescue protocol were found to be prognostic with castrated males having longer survivals than spayed females. Cats that received rescue chemotherapy had shorter first remission durations than those that did not. Prior treatment with steroids and stage were not found to be significant prognostic variables. This study characterizes gastric lymphoma treated with chemotherapy in cats. Further studies are needed to determine the comparative efficacy of surgical and chemotherapeutic treatments for feline gastric lymphoma. PMID- 24216492 TI - Use of linezolid to treat MRSP bacteremia and discospondylitis in a dog. AB - A 1.5 yr old male German shepherd dog was evaluated for recurrent intermittent episodes of fever and lethargy. Clinicopathologic abnormalities were suggestive of a discospondylitis at the seventh and eighth thoracic vertebrae. Blood and urine cultures yielded growth of methicillin-resistant Staphylococcus pseudintermedius (MRSP) that was resistant to all commonly used antibiotics. Extralabel antibiotic susceptibility testing demonstrated susceptibility of both blood and urine isolates to linezolid. The prescribed dose was extrapolated from pharmacokinetic (PK) studies and the isolate's plasma minimum inhibitory concentration (MIC). Linezolid was administered for 23 wk and resulted in successful resolution of bacteremia, bacteriuria, and discospondylitis. When justified, linezolid should be considered to treat methicillin-resistant infections. PMID- 24216493 TI - Hemorrhagic cystitis in a dog receiving carboplatin. AB - An 8 yr old castrated male Labrador retriever mixed-breed dog with osteosarcoma (OSA) of the left proximal humerus receiving carboplatin presented 10 days after the third chemotherapy treatment with hematuria, stranguria, and pollakiuria. A presumptive diagnosis of hemorrhagic cystitis was made based on clinical signs, urinalysis, and cytologic analysis of a traumatic catheterization sample. Carboplatin was removed from the chemotherapy treatment plan and was substituted with doxorubicin. The dog was treated with meloxicam for pain, and the cystitis signs subsided over a period of 4 wk. Carboplatin is commonly used as adjuvant chemotherapy for dogs with OSA following amputation and is not known to cause hematuria in dogs, although there are reports of this occurring in humans. To the authors' knowledge, there are no reports in the veterinary literature of this toxicity. PMID- 24216494 TI - Postoperative adjuvant combination therapy with doxorubicin and noncytotoxic suramin in dogs with appendicular osteosarcoma. AB - Although conventional treatment of dogs with osteosarcoma (OSA) by amputation and chemotherapy results in reported survival times (STs) of 262-413 days, no major improvements in STs have occurred in the past 2 decades. Suramin is a polysulfonated napthylurea, which at noncytotoxic concentrations in vitro, increases tumor sensitivity to chemotherapy, including doxorubicin. The study authors evaluated the combination of noncytotoxic suramin and doxorubicin after amputation in dogs with OSA. The hypothesis was that treatment of dogs with appendicular OSA with amputation, adjuvant doxorubicin, and noncytotoxic suramin would be well tolerated and result in STs at least comparable to those of doxorubicin alone. Forty-seven dogs received 6.75 mg/kg of suramin IV followed by 30 mg/m(2) of doxorubicin IV 4 hr later. Treatment was repeated q 2 wk for five doses. The median disease free time (DFI) was 203 days (range, 42-1,580+ days) and the median ST for all dogs was 369 days (range, 92-1,616+ days). There was no statistical difference in ST and DFI between greyhounds and nonngreyhounds. Adjuvant doxorubicin and noncytotoxic suramin was well tolerated in dogs with OSA following amputation. Additional studies are needed to determine if this combination treatment protocol provides additional clinical benefit compared with doxorubicin alone. PMID- 24216495 TI - Comparison of propofol and propofol/ketamine anesthesia for evaluation of laryngeal function in healthy dogs. AB - Thiopental is an excellent choice for evaluation of laryngeal function. Unfortunately, thiopental is no longer manufactured. In its absence, the ideal anesthetic protocol for laryngoscopy has not been determined. Propofol and propofol/ketamine were compared for the evaluation of laryngeal function in 48 healthy dogs. Laryngeal exposure was moderate to excellent in all dogs and not significantly different between protocols. Saturation of peripheral O2 (SPO2) readings were decreased in the propofol/ketamine group, and deeper respirations were more likely to correlate with normal laryngeal function regardless of treatment group. Doxapram was administered to apneic patients to stimulate respiration and allow for evaluation of laryngeal function. No significant difference in frequency of doxapram administration between groups was noted. Doxapram resulted in higher respiratory scores and significantly increased the ability to determine normal laryngeal function. Ketamine did not allow for a reduction in propofol dose and caused increased respiratory depression, making ketamine a poor addition to propofol for laryngeal function examination. Regardless of the protocol used, laryngeal function should be determined in conjunction with the respiratory phase and depth of respirations. Patients with either absent or shallow respirations should receive doxapram for accurate evaluation of laryngeal function. PMID- 24216496 TI - Use of IV lipid emulsion for treatment of ivermectin toxicosis in a cat. AB - Ivermectin toxicosis in cats is infrequently reported. IV lipid emulsion (ILE) is a novel treatment in veterinary medicine that has been used for amelioration of adverse effects seen with multiple lipid soluble compounds. Previously, ILE has been investigated in experimental models with rats, rabbits, pigs, and dogs, mainly for resuscitation of cardiopulmonary arrest and treatment of hypotension due to local anesthetic drug overdose. There are few case reports in veterinary medicine of using ILE for drug toxicity. Only one feline case has been reported, with IV lipids used for treatment of lidocaine toxicity. This report describes a case of ivermectin toxicosis in a 1 yr old domestic shorthair that was safely and successfully treated using ILE. PMID- 24216497 TI - The cardiovascular effects of sevoflurane and isoflurane after premedication of healthy dogs undergoing elective surgery. AB - Sevoflurane and isoflurane are commonly used in veterinary anesthesia. The objective of this prospective, randomized, open-label clinical study was to compare the cardiovascular effects of sevoflurane and isoflurane via direct arterial blood pressure measurements and the lithium dilution cardiac output (LDCO) on premedicated healthy dogs undergoing elective tibial plateau leveling osteotomy (TPLO). Nineteen client-owned dogs were included. All dogs were premedicated with hydromorphone (0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg subcutaneously). Ten dogs were anesthetized with sevoflurane and nine dogs were anesthetized with isoflurane. Eighteen dogs were instrumented with a dorsal pedal arterial catheter, and one dog had a femoral arterial catheter. All dogs had continuous, direct systolic (SAP), diastolic (DAP), and mean arterial (MAP) blood pressure readings as well as heart rate (HR), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stroke volume variation (SVV), and pulse pressure variation (PPV) recorded q 5 min during the surgical procedure. There was no significant statistical difference in all parameters between the sevoflurane and isoflurane treatment groups. Both sevoflurane and isoflurane inhalant anesthetics appear to have similar hemodynamic effects when used as part of a multimodal anesthetic protocol in premedicated healthy dogs undergoing an elective surgical procedure. PMID- 24216498 TI - Absorption of transdermal and oral cyclosporine in six healthy cats. AB - Cyclosporine is commonly used orally to treat feline dermatoses. Due to difficulties administering oral medications, veterinarians sometimes prescribe compounded transdermal cyclosporine, despite studies showing limited absorption. The study objective was to compare cyclosporine blood concentrations after oral administration to concentrations after transdermal application of cyclosporine (prepared in pluronic lecithin organogel [PLO]) in six cats using a controlled, cross-over design with a 2 wk washout period. Cats were dosed at 5.1-7.4 mg/kg of cyclosporine q 24 hr either per os for 7 days or transdermally for 21 days. Cyclosporine blood concentrations were measured q 7 days and after the washout period. A monoclonal-based immunoassay (lower limit of quantitation was 25 ng/mL) was used. Median concentrations on the seventh day were 2,208 ng/mL (range, 1,357 3,419 ng/mL) 2 hr after orally administered cyclosporine and 37 ng/mL (range, 25 290 ng/mL) 2 hr after transdermally applied cyclosporine. Median concentration on day 21 was 58 ng/mL (range, 51-878 ng/mL) 2 hr after transdermally applied cyclosporine. Concentrations were quantifiable for transdermally applied cyclosporine, but considered therapeutic in only one of six cats. Based on those results, transdermally applied cyclosporine was not recommended in cats because of inconsistent absorption. PMID- 24216499 TI - Combined use of intravesicular ureteroneocystostomy techniques to correct ureteral ectopia in a male cat. AB - A 2 yr old castrated male Himalayan presented for evaluation and treatment of persistent urinary incontinence that had been present since birth. Ultrasonographic evaluation of the urinary tract revealed suspected bilateral, extramural, ureteral ectopia that was confirmed at the time of surgical exploration. Marked left hydroureter and a normal right ureter were found entering the urethra ~ 2 cm caudal to the bladder neck. An intravesicular mucosal apposition (modified Leadbetter-Politano) and "drop-in" ureteroneocystostomy techniques were used for reimplantation of the left and right ureter, respectively. Postoperatively, the cat gained urinary continence and remained continent and clinically normal 6 mo following surgery. PMID- 24216500 TI - Canine giant hypertrophic gastritis treated successfully with partial gastrectomy. AB - A 4 yr old castrated male Jack Russell terrier was presented with a 2 mo history of vomiting, anorexia, and weight loss. Abdominal radiographs and ultrasound supported the diagnosis of gastric outflow obstruction. Celiotomy and gastrotomy revealed a large, narrowly based mass originating from the mucosa of the dorsal gastric body, occupying the lumen of the stomach and protruding through the pylorus into the duodenum. A partial gastrectomy was performed to excise the mass along with a 1 cm margin of grossly normal tissue. Giant hypertrophic gastritis was diagnosed via histopathology of the excised tissue. Giant hypertrophic gastritis is a rarely diagnosed disease of canines, characterized by giant gastric folds, hypoalbuminemia, and mucosal hypertrophy. Long-term treatment success has not been previously reported. In the case described herein, surgical excision of the affected gastric tissue provided complete resolution of clinical signs. Twelve mo following surgery, no recurrence of either vomiting or weight loss had been noted and the dog was clinically normal. PMID- 24216501 TI - 2014 AAHA weight management guidelines for dogs and cats. AB - Communicating and implementing a weight management program for dogs and cats can be a challenging endeavor for veterinarians, but a rewarding one. An effective individualized weight loss program provides a consistent and healthy rate of weight loss to reduce risk of disease, prevent malnutrition, and improve quality of life. Weight loss is achieved with appropriate caloric restriction, diet selection, exercise, and strategies to help modify behavior of both the pet and client. This document offers guidelines and tools for the management of weight loss and long-term maintenance of healthy weight. PMID- 24216502 TI - Global exponential synchronization of memristor-based recurrent neural networks with time-varying delays. AB - This paper deals with the problem of global exponential synchronization of a class of memristor-based recurrent neural networks with time-varying delays based on the fuzzy theory and Lyapunov method. First, a memristor-based recurrent neural network is designed. Then, considering the state-dependent properties of the memristor, a new fuzzy model employing parallel distributed compensation (PDC) gives a new way to analyze the complicated memristor-based neural networks with only two subsystems. Comparisons between results in this paper and in the previous ones have been made. They show that the results in this paper improve and generalized the results derived in the previous literature. An example is also given to illustrate the effectiveness of the results. PMID- 24216503 TI - Increased survival in the red flour beetle after oral priming with bacteria conditioned media. AB - Immune priming is defined as enhanced protection upon secondary exposure to a pathogen. Such enhanced resistance after prior exposure has been demonstrated for a number of insect species including the red flour beetle, Tribolium castaneum. In testing this phenomenon, the majority of studies have focused on introducing the pathogen into the insect's hemocoel via septic wounding through the cuticle. Although such septic injury can occur in nature, many pathogens enter their hosts via the oral route, i.e. by ingestion. Bacillus thuringiensis bacteria are well known insect pathogens that infect their host orally. We found that T. castaneum larvae showed increased survival after oral exposure to B. thuringiensis, when they had been orally primed with filter-sterilized media in which spores of B. thuringiensis had been raised. Such priming was achieved only with a naturally pathogenic strain of B. thuringiensis and a strain that was made pathogenic by transfer of plasmids. Moreover, primed larvae were smaller in size 24 h after priming and had a longer developmental time, indicating that investment in such a response comes at a cost. However, the increased survival in primed larvae was not caused by larval size differences upon challenge. PMID- 24216504 TI - Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a (11)C beam. AB - In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (beta+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a (11)C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min(-1), respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with (15)O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min(-1). Our present work suggested the dynamics of (11)C might be relevant to CBF or permeability of a molecule containing (11)C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer. PMID- 24216505 TI - Growth differentiation factor 15 in multiple myeloma: a microenvironment factor predictive of response to treatment? PMID- 24216506 TI - Can child temperament be related to early childhood caries? AB - Beyond the biological risk factors of early childhood caries (ECC) is child temperament. This study aimed to investigate the relationship of ECC to different traits of child temperament, directly and indirectly through the nutritional and oral hygiene habits. Through a multi-stage sampling, 373 kindergarten children aged 18-36 months participated in this study. The primary caregivers filled in the Early Childhood Behaviour Questionnaire (ECBQ) and a checklist containing demographic data and the dietary and oral hygiene habits of the children. Children were examined for dental caries. The frequency of ECC was 41.14%. With 18 aspects of a child's temperament under consideration, attentional shifting, fear, frustration, low-intensity pleasure, sadness and shyness were significantly higher in the ECC group. Cuddliness, perceptual sensitivity, positive anticipation and soothability were significantly higher in caries-free children. Attentional shifting (p = 0.02), frustration (p = 0.02) and shyness (p = 0.03) were risk factors and cuddliness (p < 0.001) was a protecting factor for ECC. In the multiple regression model regarding nutritional and oral hygiene habits, easily soothable children were 0.69 times less likely to use sweetened liquids frequently [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.49-0.97, p = 0.03], while sad children were 0.58 times less likely to brush (OR 0.58, 95% CI 0.36-0.94, p = 0.02). Considering temperament traits along with socioeconomic status, positive anticipation was the most significant determinant of ECC (OR 1.57, 95% CI 1.13-2.19, p = 0.007). However, considering temperament, socioeconomic measures and child habits among ECC risk factors, the most significant was the initiation of brushing habits (OR 5.41, 95% CI 2.81-12.98, p = 0.002). PMID- 24216507 TI - Induction of myelodysplasia by myeloid-derived suppressor cells. AB - Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33's immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-beta by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif-bearing (ITAM bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS. PMID- 24216508 TI - NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. AB - ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4(-/-) mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy-induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis. PMID- 24216509 TI - Type III TGF-beta receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma. AB - Growth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the pediatric tumor neuroblastoma remain unclear. Comparison of mRNA from benign neuroblastic tumors and neuroblastomas revealed that expression of the type III TGF-beta receptor (TGFBR3) decreases with advancing stage of neuroblastoma and this loss correlates with a poorer prognosis. Patients with MYCN oncogene amplification and low TGFBR3 expression were more likely to have an adverse outcome. In vitro, TbetaRIII expression was epigenetically suppressed by MYCN-mediated recruitment of histone deacetylases to regions of the TGFBR3 promoter. TbetaRIII bound FGF2 and exogenous FGFR1, which promoted neuronal differentiation of neuroblastoma cells. TbetaRIII and FGF2 cooperated to induce expression of the transcription factor inhibitor of DNA binding 1 via Erk MAPK. TbetaRIII-mediated neuronal differentiation suppressed cell proliferation in vitro as well as tumor growth and metastasis in vivo. These studies characterize a coreceptor function for TbetaRIII in FGF2-mediated neuronal differentiation, while identifying potential therapeutic targets and clinical biomarkers for neuroblastoma. PMID- 24216510 TI - Hirschsprung-like disease is exacerbated by reduced de novo GMP synthesis. AB - Hirschsprung disease (HSCR) is a partially penetrant oligogenic birth defect that occurs when enteric nervous system (ENS) precursors fail to colonize the distal bowel during early pregnancy. Genetic defects underlie HSCR, but much of the variability in the occurrence and severity of the birth defect remain unexplained. We hypothesized that nongenetic factors might contribute to disease development. Here we found that mycophenolate, an inhibitor of de novo guanine nucleotide biosynthesis, and 8 other drugs identified in a zebrafish screen impaired ENS development. In mice, mycophenolate treatment selectively impaired ENS precursor proliferation, delayed precursor migration, and induced bowel aganglionosis. In 2 different mouse models of HSCR, addition of mycophenolate increased the penetrance and severity of Hirschsprung-like pathology. Mycophenolate treatment also reduced ENS precursor migration as well as lamellipodia formation, proliferation, and survival in cultured enteric neural crest-derived cells. Using X-inactivation mosaicism for the purine salvage gene Hprt, we found that reduced ENS precursor proliferation most likely causes mycophenolate-induced migration defects and aganglionosis. To the best of our knowledge, mycophenolate is the first medicine identified that causes major ENS malformations and Hirschsprung-like pathology in a mammalian model. These studies demonstrate a critical role for de novo guanine nucleotide biosynthesis in ENS development and suggest that some cases of HSCR may be preventable. PMID- 24216511 TI - Allogeneic T cell responses are regulated by a specific miRNA-mRNA network. AB - Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses. PMID- 24216513 TI - Sound preconditioning therapy inhibits ototoxic hearing loss in mice. AB - Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug-induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs. PMID- 24216512 TI - Chronic itch development in sensory neurons requires BRAF signaling pathways. AB - Chronic itch, or pruritus, is associated with a wide range of skin abnormalities. The mechanisms responsible for chronic itch induction and persistence remain unclear. We developed a mouse model in which a constitutively active form of the serine/threonine kinase BRAF was expressed in neurons gated by the sodium channel Nav1.8 (BRAF(Nav1.8) mice). We found that constitutive BRAF pathway activation in BRAF(Nav1.8) mice results in ectopic and enhanced expression of a cohort of itch sensing genes, including gastrin-releasing peptide (GRP) and MAS-related GPCR member A3 (MRGPRA3), in nociceptors expressing transient receptor potential vanilloid 1 (TRPV1). BRAF(Nav1.8) mice showed de novo neuronal responsiveness to pruritogens, enhanced pruriceptor excitability, and heightened evoked and spontaneous scratching behavior. GRP receptor expression was increased in the spinal cord, indicating augmented coding capacity for itch subsequent to amplified pruriceptive inputs. Enhanced GRP expression and sustained ERK phosphorylation were observed in sensory neurons of mice with allergic contact dermatitis- or dry skin-elicited itch; however, spinal ERK activation was not required for maintaining central sensitization of itch. Inhibition of either BRAF or GRP signaling attenuated itch sensation in chronic itch mouse models. These data uncover RAF/MEK/ERK signaling as a key regulator that confers a subset of nociceptors with pruriceptive properties to initiate and maintain long-lasting itch sensation. PMID- 24216515 TI - High glucose concentration does not modulate the formation of arterial medial calcification in experimental uremic rats. AB - High phosphate-induced phenotypic switching of smooth muscle cells (SMCs) into osteogenic cells is critical for the formation of arterial medial calcification in chronic kidney disease. Because vascular calcification is also prevalent in type 2 diabetes, we examined whether glucose concentration affects high phosphate induced SMC phenotypic switching and calcification. First, the formation of arterial medial calcification was compared among 4 groups: adenine-fed uremic rats, streptozotocin-injected hyperglycemic rats, adenine-fed and streptozotocin injected uremic/hyperglycemic rats, and control rats. Calcification was obvious in uremic and uremic/hyperglycemic rats, whereas it was undetectable in the others. Aortic calcium contents were significantly elevated in uremic and uremic/hyperglycemic rats, but they were not different between the two groups. Moreover, hyperglycemia had no effects on the reduced expression of SMC differentiation markers including smooth muscle alpha-actin and SM22alpha and on the increased expression of osteogenic markers, such as Runx2, in uremic rats. Second, cultured SMCs were incubated in the medium with various concentrations of phosphate (0.9-4.5 mmol/l) and glucose (5-50 mmol/l), and calcium deposition was measured. Although high phosphate dose-dependently increased calcium contents, they were unaffected by glucose concentration. Results suggest that glucose concentration does not directly modulate high phosphate-induced SMC phenotypic switching and arterial medial calcification. PMID- 24216516 TI - Tularemia outbreaks in Kayseri, Turkey: an evaluation of the effect of climate change and climate variability on tularemia outbreaks. AB - OBJECTIVES: The aim of this study was to evaluate the epidemiological characteristics of tularemia outbreak and the effect of climate variability on this outbreak in Kayseri. METHODS: The outbreak places, infection dates, source of infection, and the number of cases were recorded and analyzed. This information was obtained from the Regional Public Health Department. Climate data were supplied by the Regional Meteorological Service. RESULTS: The first case in Sariz was recorded in 2005. Thereafter, 2 cases were reported in 2006 and 1 case in 2007. During 2010, 21 cases were recorded in 7 towns, 62 cases in 2011 and 27 cases in 2012. A total number of 110 cases were recorded in 12 out of 16 towns in Kayseri Province between 2010 and 2012. The majority of cases were seen in the north-eastern, east and south-eastern parts of Kayseri Province; located in higher altitudes (over 1000m from sea level). It was accepted that the outbreak was originated from water sources and was confirmed by few number of water samples collected from outbreak areas. Considering climate variations, the outbreak occurred between 1988 and 2009 during a dry, low humid, high temperature period after rainy season. CONCLUSION: A tularemia outbreak was observed between 2010 and 2012 with the initiation of rainy years. High temperature for a long period accompanied by low rainfall and low humidity may affect the vector's biology and initiate a tularemia outbreak in high plateaus in Kayseri Province and around. PMID- 24216514 TI - A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells. AB - Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre-B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue specific heterodimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors. PMID- 24216517 TI - The first reported case of possible Haemophilus influenzae type b vaccine failure from Kuwait and literature-review. AB - A 17-month-old vaccinated Kuwaiti boy presented with meningitis. The Haemophilus influenzae type b (Hib) capsular antigen was detected in his blood, CSF and urine. The microorganism failed to grow in culture. This case represents the first report of possible Hib vaccine failure from Kuwait. This report examines the possible reasons for this failure by reviewing the literature and emphasizes the need to broaden the definition of vaccine failure with the aim of optimizing the timing of the vaccine booster dose for prematurely born children and establishing continuous surveillance for Hib vaccine failure. PMID- 24216518 TI - Current status and future trends in the diagnosis and treatment of drug susceptible and multidrug-resistant tuberculosis. AB - The global burden of tuberculosis (TB) is still large. The increasing incidence of drug-resistant, multidrug-resistant (MDR) (resistant to at least rifampicin and isoniazid), and extensively drug-resistant (XDR) (additionally resistant to a fluoroquinolone and kanamycin/amikacin/capreomycin) strains of Mycobacterium tuberculosis and the association of active disease with human immunodeficiency virus coinfection pose a major threat to TB control efforts. The rapid detection of M. tuberculosis strains and drug susceptibility testing (DST) for anti-TB drugs ensure the provision of effective treatment. Rapid molecular diagnostic and DST methods have been developed recently. Treatment of drug-susceptible TB is effective in >=95% of disease cases; however, supervised therapy for >=6 months is challenging. Non-adherence to treatment often results in the evolution of drug resistant strains of M. tuberculosis due to mutations in the genes encoding drug targets. Sequential accumulation of mutations results in the evolution of MDR and XDR strains of M. tuberculosis. Effective treatment of MDR-TB involves therapy with 5-7 less effective, expensive, and toxic second-line and third-line drugs for >=24 months and is difficult in most developing countries. XDR-TB is generally an untreatable disease in developing countries. Some currently existing drugs and several new drugs with novel modes of action are in various stages of development to shorten the treatment duration of drug-susceptible TB and to improve the outcome of MDR-TB and XDR-TB. PMID- 24216519 TI - The need for antimicrobial stewardship: a public health concern. PMID- 24216520 TI - A miniature optical neuronavigation system for CT-guided stereotaxy. AB - BACKGROUND AND OBJECTIVE: Neuronavigation devices have progressed over the past 2 decades, but logistical limitations remain for many stereotactic procedures. We describe our technique and accuracy for a novel miniature optical tracking system which overcomes these limitations. METHOD: The minioptical tracking system uses a miniature video camera mounted on a rigid cannula to determine cannula location and orientation relative to a patient-attached sticker containing reference markers. A CT scan is used to register these markers to the anatomy and a user selected target. A computer displays the cannula guidance information to the target. Bench testing was performed on 225 targets in a custom test phantom and additional testing was performed on 20 small targets in an anthropomorphic head phantom to determine the practical accuracy and workflow. RESULTS: The phantom study demonstrated that 3-D navigation accuracy is 1.41 +/- 0.53 mm. There was a 100% head phantom study success rate for the 20 small targets. CONCLUSIONS: The resulting accuracy data demonstrated good correlation with the CT data, and the clinical simulation workflow indicated its potential usefulness for common neurosurgical applications. Furthermore, this small-footprint tracking technology does not experience the traditional environmentally induced issues or the requirement of pin-based head fixation, allowing for use in the neurointensive care unit and the emergency department. PMID- 24216521 TI - Successful ablation of a narrow complex tachycardia arising from a left ventricular false tendon: mapping and optimizing energy delivery. PMID- 24216522 TI - Esophageal nightmare: cancer recurrence after definitive chemoradiation. Is salvage esophagectomy possible? AB - Salvage esophagectomy is a rare treatment option in patients failing definitive treatment of esophageal cancer. The ideal patient has recurrent cancer with a long disease-free interval. R0 resection is necessary if long-term survival is to be realized. Patients with small recurrent cancers without M1, T4, or N+ disease are most likely to benefit from salvage esophagectomy. Complications are frequent and are typically pulmonary or anastomotic. Mortality is significant, with 25% 35% survival at most following R0 resection. Most deaths are secondary to cancer or salvage esophagectomy. R1 and R2 resections are to be avoided. Better multimodality treatment planning would eliminate the "nightmare" of salvage esophagectomy. PMID- 24216524 TI - Lobar lung transplantation: emerging evidence for a viable option. AB - The field of lung transplantation has seen an exciting evolution recently, with novel approaches to increasing the number of organs available for patients with end-stage lung disease. We review 2 recent reports describing the approach of lobar lung transplant as a successful and viable option for those recipients who are challenged by size mismatch and clinical course decline while on the transplant waiting list. PMID- 24216523 TI - Women and lung cancer: what is new? AB - In the last 20 years, there has been an increased focus on gender differences in health and disease. The earliest studies of lung cancer enrolled mainly men, as the incidence of lung cancer among women was exceedingly low. As social patterns changed around World War II and women began to smoke more, the epidemiology of lung cancer has changed. The higher percentage of lung cancer in nonsmoking women as compared with nonsmoking men suggests that lung cancer behaves differently in women. Studies of lung cancer in women indicate that there are differences in risk factors, histology, pathophysiology, treatment outcomes, and prognosis as compared with men. The purpose of this review is to provide a concise summary of the literature on lung cancer as it pertains to women, with an emphasis on new areas of research and treatment options. PMID- 24216525 TI - Coronary artery bypass graft surgery remains the standard of care for patients with diabetes. AB - Coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are proven effective treatments of coronary artery disease (CAD), however, the optimal revascularization strategy remains unclear in certain patient subsets. The recently published "Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM)" trial is a randomized study evaluating the use of CABG vs PCI in diabetic patients with multivessel coronary disease. The purpose of this editorial is to review the FREEDOM trial and the available literature guiding clinicians to make evidence-based decisions when treating diabetic patients with multivessel coronary disease. The current evidence suggests that CABG should remain the standard of care for this patient population. PMID- 24216526 TI - Berlin Heart EXCOR Food and Drug Administration Investigational Device Exemption Trial. PMID- 24216527 TI - Open aortic arch repair: state-of-the-art and future perspectives. AB - Surgical procedures for the treatment of complex aortic arch pathology remain among the most challenging cardiovascular operations, incurring considerable risk for death and stroke. The purpose of this article is to describe the evolution of our approach to open repair of the aortic arch. Our arterial cannulation strategy has shifted from femoral and direct aortic to right axillary and more recently innominate artery cannulation. This transition has facilitated the administration of continuous antegrade cerebral perfusion and more moderate levels of hypothermia during complex repairs. Modifications in surgical technique, including arch reconstruction with the trifurcated graft, and the classical and frozen elephant trunk techniques have simplified the conduct of the operation. Experimental and clinical research supporting the evolution of our approach is discussed in this paper. PMID- 24216528 TI - The state of the art in preventing postthoracotomy pain. AB - Pain after thoracic surgery can be intense and prolonged. Inadequate pain management can have several detrimental effects, including increased postoperative morbidity and delayed recovery as well as occurrence of postthoracotomy syndrome. Therefore, establishing an adequate analgesic regimen for thoracic surgery is critical. Thoracic paravertebral block or thoracic epidural analgesia is recommended as the first-choice therapies for postthoracotomy analgesia. When these techniques are either contraindicated or not possible, intercostal analgesia or intrathecal opioids are recommended. These techniques should be combined with nonopioid analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2-specific inhibitors, administered on a regular "round-the-clock" basis, with opioids used as "rescue" analgesics. Finally, the integration of multimodal analgesia techniques with multidisciplinary rehabilitation program can enhance recovery, reduce hospital stay, and facilitate early convalescence. PMID- 24216529 TI - The state of the art in the technical performance of lung-sparing operations for malignant pleural mesothelioma. AB - Malignant pleural mesothelioma remains an incurable disease for which the role of surgery remains controversial. Though not yet clearly defined there does appear to be a subset of patients who benefit from a surgery-based multimodal treatment plan, beyond what would be expected with current nonoperative therapies. As with other pleural cancers it is probably not possible to achieve a microscopic complete resection with any operation. The goal of surgery in this setting, therefore, is to remove all visible and palpable disease - a macroscopic complete resection. There are basically two surgical approaches to achieve a macroscopic complete resection, lung-sacrificing and lung-sparing. Lung-sacrificing surgery, which likely leaves behind the least amount of microscopic disease, is accomplished as an extrapleural pneumonectomy. This is a well established and standardized operation. Lung-sparing surgery for malignant pleural mesothelioma, on the other hand, does not currently enjoy any degree of consistency. Not only are the reported variations on the operation widely disparate, but even the nomenclature to describe the operation is highly variable. Often the selection of a lung-sparing approach is reported as an intraoperative decision that hinges on the bulk of the cancer and/or the degree of extension into the pulmonary fissures. This article describes the current evolution of a lung-sparing procedure, radical pleurectomy, which has been used to achieve a macroscopic complete resection in over a hundred patients. Many of these cases involved bulky cancers, some exceeding two liters in volume, and often with extensive invasion of the pulmonary fissures. With the described technique there has not yet been an instance where conversion to extrapleural pneumonectomy would have contributed to the ability to achieve a macroscopic complete resection. Whether or not radical pleurectomy is the optimal approach for any or all patients undergoing surgery based multimodal treatment for malignant pleural mesothelioma is not known, but the described technique does offer an operation that can serve as a consistent foundation for any surgery-based treatment strategy where achieving a macroscopic complete resection, while sparing the lung, is desired. PMID- 24216530 TI - Current readings: The most influential and recent studies involving surgical management of thymoma. AB - Thymic epithelial tumors can be challenging to manage because of local invasion of mediastinal structures and high recurrence rates. Surgery is the mainstay of treatment and complete resection is associated with the best prognosis. Although practices vary, neoadjuvant chemotherapy is often used to improve resectability. Extended resections following neoadjuvant treatment have been safely performed for locally advanced tumors. R0 resection should be the goal and should dictate the surgical approach and extent of resection. Postoperative radiation therapy has often been used to reduce the risk of recurrence after resection. No study has definitively shown a recurrence or survival benefit with postoperative radiation therapy in completely resected tumors. However, there are some data to support its use in patients with residual disease. As our knowledge has largely been derived from small series, larger multicenter collaborative efforts are needed to improve our understanding of this disease. PMID- 24216531 TI - Current readings: Endoesophageal management of early esophageal cancer and dysplastic barrett esophagus: a review of recent and influential studies. PMID- 24216532 TI - Current readings: Surgical management of heart failure. AB - There are a myriad of surgical therapies for patients with end-stage congestive heart failure. Coronary revascularization and mitral valve repair have clear clinical benefits in appropriately selected patients. Further investigation is required before the widespread adoption of volume-reduction strategies. Cardiac stem cell therapies have yielded promising results in preclinical and phase I studies. PMID- 24216533 TI - Current readings: Status of robotic cardiac surgery. AB - Robotic surgery has been applied to various fields in cardiac surgery. Despite excellent results published in the literature, critics have questioned procedure reproducibility, increased cost, and the real patient benefit. We reviewed 5 recent articles to show that robotic cardiac surgery likely will play an important role in the new era of cardiac surgery. PMID- 24216534 TI - Quality improvement in cardiac surgery: January 30, 2013, Los Angeles, CA. PMID- 24216535 TI - Determination by LC-MS/MS of colistins A and B in plasma and ultrafiltrate from critically ill patients undergoing continuous venovenous hemodiafiltration. AB - BACKGROUND: Colistin is a 50-year-old antibiotic, the use of which was ceased in the 70s and recently resumed as a "salvage therapy" against multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii. The narrow therapeutic range of colistin makes the choice of its correct dosage crucial, and monitoring of blood concentration is occasionally necessary for critically ill patients, including intensive care patients subjected to continuous renal replacement therapy. METHODS: Two LC-MS/MS methods were developed and fully validated for the quantitative determination of colistins A and B in plasma and dialysis ultrafiltrate (UF) samples, ultimately arising from 4 patients undergoing continuous venovenous hemodiafiltration (CVVHDF). RESULTS: The developed methods proved to be both specific and selective. They showed good fit and linearity over the entire range of interest. Trueness and accuracy proved satisfactory. Both methods have excellent intraassay precision (percent coefficient of variations were lower than 10%) and limit of detection values in the range 20-100 ng/mL, about 1-2 orders of magnitude below the concentrations commonly detected in real samples. The mean sieving coefficient (SC) values, measured after 10 minutes of CVVHDF, were 0.42 for colistin A and 0.48 for colistin B. SC values proved to be quite stable for 24 hours, but then declined to 0.24 for colistin A and 0.32 for colistin B, respectively, after 48 hours. At the median blood flow and effluent flow rate of 120 and 28 mL/min, clearance values for colistin B were higher than 15 mL/min. During the entire duration of CVVHDF sessions, the SC and clearance values for colistin A were significantly lower than colistin B. CONCLUSIONS: Two simple methods for the simultaneous determination of colistins A and B have been developed and validated. Their application in the clinical setting demonstrates that CVVHDF treatment lasting 48 hours produces a relatively constant and efficient removal of the drug. PMID- 24216536 TI - The detection of cortisol in human sweat: implications for measurement of cortisol in hair. AB - BACKGROUND: Hair cortisol analysis has been shown to be an effective measure of chronic stress. Cortisol is assumed to incorporate into hair via serum, sebum, and sweat sources; however, the extent to which sweat contributes to hair cortisol content is unknown. METHODS: Sweat and saliva samples were collected from 17 subjects after a period of intensive exercise and analyzed by salivary enzyme-linked immunosorbent assay (ELISA). Subsequently, an in vitro test on exposure of hair to hydrocortisone was conducted. Residual hair samples were immersed in a 50-ng/mL hydrocortisone solution for periods lasting 15 minutes to 24 hours, followed by a wash or no-wash condition. Hair cortisol content was determined using our modified protocol for a salivary ELISA. RESULTS: Postexercise control sweat cortisol concentrations ranged from 8.16 to 141.7 ng/mL and correlated significantly with the log-transformed time of day. Sweat cortisol levels significantly correlated with salivary cortisol concentrations. In vitro hair exposure to a 50-ng/mL hydrocortisone solution (mimicking sweat) for 60 minutes or more resulted in significantly increased hair cortisol concentrations. Washing with isopropanol did not affect immersion-increased hair cortisol concentrations. CONCLUSIONS: Human sweat contains cortisol in concentrations comparable with salivary cortisol levels. This study suggests that perfuse sweating after intense exercise may increase cortisol concentrations detected in hair. This increase likely cannot be effectively decreased with conventional washing procedures and should be considered carefully in studies using hair cortisol as a biomarker of chronic stress. PMID- 24216537 TI - Development and validation of a new ultra-performance liquid chromatographic method for vancomycin assay in serum and its application to therapeutic drug monitoring. AB - OBJECTIVE: The aim of this study was to develop and validate an ultra-performance liquid chromatographic (UPLC) method with photodiode array detector for the measurement of vancomycin in human serum samples for therapeutic drug monitoring or other applications. METHODS: The method included the extraction of vancomycin in serum by deproteinization with acetonitrile. The analyses were carried out using an ACQUITY UPLC BEH C(18) column (2.1 * 50 mm, 1.7 MUm) using acetonitrile and 0.005 M KH(2)PO(4) buffer (pH 2.5) as the mobile phase at a flow rate of 0.3 mL/min, with photodiode array detection at 230 nm. The method was validated for extraction recovery, inter- and intraday precision (relative standard deviation, RSD%), and accuracy and stability of vancomycin in serum. Both the established UPLC method and fluorescence polarization immunoassay (FPIA) were used to measure the prepared quality control (QC) samples (1.0, 7.0, 35.0, 75.0 mg/L) to validate the accuracy of UPLC. Furthermore, both methods were subsequently used to assay the vancomycin concentration in 172 clinical serum samples collected from patients receiving vancomycin in the hospitals localized in Shanghai (China) and 32 control samples from United Kingdom National External Quality Assessment Service (UK NEQAS). RESULTS: The retention time of vancomycin was 2.6 minutes. The calibration curve for UPLC was linear over the range 1.0-100.0 mg/L (R(2) > 0.999). The method was fully validated in terms of recovery, selectivity, accuracy, precision, and various conditions. The absolute difference% and RSD% of the prepared QC samples assayed by UPLC were all better than the results by FPIA. A paired t test of the results of the prepared QC samples indicated that the results of all the QC samples had significant difference (P < 0.05), except for the 7.0 mg/L QC samples, which suggested that UPLC was more accurate for the samples containing low or high concentration of vancomycin. A correlation with the Deming model provided a good linear relation between the results of the 2 methods applied to 172 samples, with equation of UPLC = 0.99 * FPIA - 0.19 (R(2)= 0.923), and the agreement of the 2 methods was illustrated using Bland-Altman plot with a mean difference (UPLC - FPIA) of -0.428 mg/L and 95% confidence interval of -8.33 to 7.47 mg/L, respectively. A Student t test comparing results obtained by the UPLC method and group mean results of control samples from UK NEQAS were not significant (P = 0.057). CONCLUSIONS: A short analysis time, small amount of serum needed, high specificity, and accuracy make the UPLC method developed in this study appropriate and practical for vancomycin therapeutic drug monitoring and could be applied to other nonserum applications or where requiring superior validation parameters such as for pharmacokinetic/pharmacodynamic studies. PMID- 24216538 TI - Abnormal default-mode network homogeneity in first-episode, drug-naive schizophrenia at rest. AB - BACKGROUND: Dysconnectivity hypothesis posits that schizophrenia relates to abnormal resting-state connectivity within the default-mode network (DMN) and this aberrant connectivity is considered as contribution of difficulties in self referential and introspective processing. However, little is known about the alterations of the network homogeneity (NH) of the DMN in schizophrenia. In the present study, we used an automatic NH method to investigate the NH of the DMN in schizophrenia patients at rest. METHODS: Forty-nine first-episode, drug-naive schizophrenia patients and 50 age-, gender-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). An automated NH approach was used to analyze the data. RESULTS: Patients exhibited lower NH than controls in the left medial prefrontal cortex (MPFC) and the right middle temporal gyrus (MTG). Significantly higher NH values in the left posterior cingulate cortex (PCC) and the right cerebellum Crus I were found in the patient group than in the control group. No significant correlation was found between abnormal NH values and Positive and Negative Symptom Scale (PANSS) scores, duration of untreated psychosis (DUP), age or years of education in the patient group. CONCLUSIONS: Our findings suggest that abnormal NH of the DMN exists in first-episode, drug-naive schizophrenia and further highlight the importance of the DMN in the pathophysiology of schizophrenia. PMID- 24216539 TI - Trajectory and correlates of growth of extremely-low-birth-weight adolescents. AB - BACKGROUND: Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch up among extremely-low-birth-weight (ELBW) (<1 kg) adolescents. METHODS: A cohort study of 148 neurologically normal ELBW children and 115 normal-birth-weight (NBW) controls born during the period 1992-1995 was conducted. Longitudinal measures of gender-specific growth of ELBW children from birth, in addition to growth and measures of obesity of ELBW and NBW children at 14 y, were evaluated. RESULTS: Following neonatal growth failure, ELBW children had accelerated growth, but at 8 y, they still had lower weight and height z scores than NBW children. By 14 y, ELBW boys had caught up in growth to their NBW controls, but ELBW girls remained significantly smaller. ELBW children, however, did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses, only maternal BMI and weight gain during infancy and childhood predicted the ELBW children's 14-y weight z scores, BMI z scores, and abdominal circumference. Perinatal risk factors, including intrauterine growth, only predicted growth up to 20 mo. CONCLUSION: Maternal BMI and rate of growth, rather than perinatal factors, predict 14-y obesity among neurologically normal ELBW adolescents. PMID- 24216540 TI - Metabolomics of prematurity: analysis of patterns of amino acids, enzymes, and endocrine markers by categories of gestational age. AB - BACKGROUND: Prematurity may influence the levels of amino acids, enzymes, and endocrine markers obtained through newborn screening. Identifying which analytes are the most affected by degree of prematurity could provide insight into how prematurity impacts metabolism. METHODS: Analytes from blood spots assayed by Newborn Screening Ontario between March 2006 and April 2009 were used in this analysis. We examined the associations between the degree of prematurity and the levels of amino acids, enzymes, and endocrine markers in all newborns with and without adjustment for birth weight, feeding status, sample timing, transfusion, and sex. RESULTS: Our analysis included the following cohorts: 373,819 children born at term (>36 wk gestation), 26,483 near-term children (33-36 wk gestation), 4,354 very premature children (28-32 wk gestation), and 1,146 extremely premature children (<28 wk gestation). Of the amino acids showing consistent trends across categories of prematurity, the levels of three amino acids (arginine, leucine, and valine) were at least 50% different between the cohorts of extremely premature and term children. The levels of 17-hydroxyprogesterone increased with increasing prematurity, while thyrotropin-stimulating hormone values consistently decreased with increasing prematurity. None of the three enzyme markers we examined showed a trend in levels across categories of prematurity. CONCLUSION: This study demonstrates that children at different stages of prematurity are metabolically distinct. Future research should focus on the mechanism by which specific analytes are influenced by prematurity. PMID- 24216541 TI - Pharmacodynamically optimized erythropoietin treatment combined with phlebotomy reduction predicted to eliminate blood transfusions in selected preterm infants. AB - BACKGROUND: Preterm very-low-birth-weight (VLBW) infants weighing <1.5 kg at birth develop anemia, often requiring multiple red blood cell transfusions (RBCTx). Because laboratory blood loss is a primary cause of anemia leading to RBCTx in VLBW infants, our purpose was to simulate the extent to which RBCTx can be reduced or eliminated by reducing laboratory blood loss in combination with pharmacodynamically optimized erythropoietin (Epo) treatment. METHODS: Twenty-six VLBW ventilated infants receiving RBCTx were studied during the first month of life. RBCTx simulations were based on previously published RBCTx criteria and data-driven Epo pharmacodynamic optimization of literature-derived RBC life span and blood volume data corrected for phlebotomy loss. RESULTS: Simulated pharmacodynamic optimization of Epo administration and reduction in phlebotomy by >= 55% predicted a complete elimination of RBCTx in 1.0-1.5 kg infants. In infants <1.0 kg with 100% reduction in simulated phlebotomy and optimized Epo administration, a 45% reduction in RBCTx was predicted. The mean blood volume drawn from all infants was 63 ml/kg: 33% required for analysis and 67% discarded. CONCLUSION: When reduced laboratory blood loss and optimized Epo treatment are combined, marked reductions in RBCTx in ventilated VLBW infants were predicted, particularly among those with birth weights >1.0 kg. PMID- 24216542 TI - Quantitative modeling of clinical, cellular, and extracellular matrix variables suggest prognostic indicators in cancer: a model in neuroblastoma. AB - BACKGROUND: Risk classification and treatment stratification for cancer patients is restricted by our incomplete picture of the complex and unknown interactions between the patient's organism and tumor tissues (transformed cells supported by tumor stroma). Moreover, all clinical factors and laboratory studies used to indicate treatment effectiveness and outcomes are by their nature a simplification of the biological system of cancer, and cannot yet incorporate all possible prognostic indicators. METHODS: A multiparametric analysis on 184 tumor cylinders was performed. To highlight the benefit of integrating digitized medical imaging into this field, we present the results of computational studies carried out on quantitative measurements, taken from stromal and cancer cells and various extracellular matrix fibers interpenetrated by glycosaminoglycans, and eight current approaches to risk stratification systems in patients with primary and nonprimary neuroblastoma. RESULTS: New tumor tissue indicators from both fields, the cellular and the extracellular elements, emerge as reliable prognostic markers for risk stratification and could be used as molecular targets of specific therapies. CONCLUSION: The key to dealing with personalized therapy lies in the mathematical modeling. The use of bioinformatics in patient-tumor microenvironment data management allows a predictive model in neuroblastoma. PMID- 24216543 TI - Effects on growth and tolerance and hypoallergenicity of an amino acid-based formula with synbiotics. AB - BACKGROUND: To evaluate the effects of an amino acid-based formula (AAF) with synbiotics on growth and tolerance in healthy infants. The hypoallergenicity of this AAF with synbiotics was evaluated in subjects with cow's milk allergy (CMA). METHODS: Study 1: 115 full-term, healthy infants randomly received an AAF with synbiotics or a commercially available AAF for 16 wk. Subjects' weight, length, and head circumference were primary outcome measures. Stool characteristics and gastrointestinal (GI) symptoms were secondary outcome measures. Clinical examinations, dietary intake, clinical laboratory results, and adverse events were recorded. Study 2: hypoallergenicity of the AAF with synbiotics was evaluated in 30 infants and children with immunoglobulin E (IgE)-mediated CMA using a double-blind, placebo-controlled food challenge, and a 7-d feeding period. RESULTS: Study 1: comparable results in growth parameters and tolerance were observed for both groups. Minimal differences were observed in stool characteristics and GI symptoms throughout the study. Study 2: all 30 subjects with IgE-mediated CMA completed the study with no allergic reactions detected to challenges. CONCLUSION: These studies demonstrate that an AAF with synbiotics is safe and well tolerated and promotes normal growth when fed to healthy full-term infants as the sole source of nutrition and is hypoallergenic in subjects with CMA. PMID- 24216544 TI - Abstracts of the 37th National Congress of the Italian Association for the Study of the Pancreas (AISP). Bologna, Italy. September 19-21, 2013. PMID- 24216545 TI - HBV- and HCV-related infections and risk of pancreatic cancer. AB - Pancreatic carcinoma is one of the most lethal cancers in humans. The poor prognosis of this malignancy depends on several factors, such as: lack of early symptoms, advanced stage at detection, early metastatic spread and no effective systemic treatment. To date, only few risk factors for this malignancy are known; therefore, considerable efforts are required to identify additional causative agents involved in the process of pancreatic carcinogenesis. In the last years, a large series of epidemiological investigations have suggested that both bacteria and viruses may play a important role in the initiation and progression of several animal and human cancers. In particular, some studies have showed that hepatitis B (HBV) and hepatitis C (HCV) viruses, two hepatotropic pathogens with well-known oncogenic properties for liver, may be detected also in extra-hepatic tissues, such as pancreas. The aim of this paper is to briefly report the results of available studies, assessing the possible association between HBV/HCV and pancreatic cancer development as well as to discuss the limiting factors of these researches. PMID- 24216546 TI - Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis. AB - CONTEXT: Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris(r), Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris(r) may precipitate bleeding from the inflamed pancreas. OBJECTIVE: This study tests the hypothesis that Xigris(r) can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. METHODS: Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris(r) 500 ug/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris(r) 500 ug/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. RESULTS: Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris(r) both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris(r). Pre-treatment with Xigris(r) was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris(r) was administered after induction of acute pancreatitis. CONCLUSION: Xigris(r) did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris(r) prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was not seen with administration of Xigris(r) after induction of acute pancreatitis. PMID- 24216547 TI - Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies. AB - CONTEXT: For patients with borderline resectable pancreatic cancer, the benefit of neoadjuvant therapy remains to be defined. OBJECTIVE: We did a systematic search of the literature on this topic. METHODS: Prospective studies where chemotherapy with or without radiotherapy was given before surgery to patients with borderline resectable cancer, were analyzed by a meta-analytical approach. MAIN OUTCOME MEASURES: Primary outcome was surgical exploration and resection rates; tumor response, therapy-induced toxicity, and survival were secondary outcomes. Data were expressed as weighted pooled proportions with 95% confidence intervals (95% CI). RESULTS: Ten studies with 182 participants were included. Following treatment, 69% of patients (95% CI: 56-80%) were brought to surgery and 80% (95% CI: 66-90%) of surgically-explored patients were resected. Eighty-three percent (95% CI: 74-90%) of resected specimens were deemed R0 resections. The weighted fractions of resected patients alive at 1 and 2 years were 61% (95% CI: 48-100%) and 44% (95% CI: 32-59%), respectively. At restaging following neoadjuvant therapy, weighted frequencies for complete/partial response were 16% (95% CI: 9-28%), 69% (95% CI: 60-76%) for stable disease, and 19% (95% CI: 13 25%) for progressive cancer. Treatment-related grade 3-4 toxicity was 32% (95% CI: 21-45%). CONCLUSION: This meta-analysis shows that downstaging of the lesion following neoadjuvant therapies is uncommon for patients with borderline resectable pancreatic cancer. A clear benefit of this regimen could be to spare surgery to patients with progressive disease during the frame-time chemo radiotherapy is being delivered. PMID- 24216548 TI - Recognition of complications after pancreaticoduodenectomy for cancer determines inpatient mortality. AB - CONTEXT: While perioperative mortality after pancreaticoduodenectomy is decreasing, key factors remain to be elucidated. OBJECTIVE: The purpose of this study was to investigate inpatient mortality after pancreaticoduodenectomy in the Nationwide Inpatient Sample (NIS), a representative inpatient database in the USA. METHODS: Patient discharge data (diagnostic and procedure codes) and hospital characteristics were investigated for years 2009 and 2010. The inclusion criteria were a procedure code for pancreaticoduodenectomy, elective procedure, and a pancreatic or peripancreatic cancer diagnosis. Chi-square test determined statistical significance. A logistic regression model for mortality was created from significant variables. RESULTS: Two-thousand and 958 patients were identified with an average age of 65+/-12 years; 53% were male. The mean length of stay was 15+/-12 days with a mortality of 4% and a complication rate of 57%. Eighty-six percent of pancreaticoduodenectomy occurred in teaching hospitals. Pancreaticoduodenectomy performed in teaching hospitals in the first half of the academic year were associated with higher mortality than in the latter half (5.5% vs. 3.4%, P=0.005). On logistic regression analysis, non-surgical complications are the largest predictor of death (P<0.001) while operations in the latter half of the academic year are associated with decreased mortality (P<0.01). CONCLUSIONS: The timing of pancreaticoduodenectomy for cancer remained more predictive of mortality than age or length of stay; only complications were more predictive of death than time of year. This suggests that there remains a clinically and statistically significant learning curve for trainees in identifying complications; further study is needed to prove that identification of complications leads to a decrease in mortality rate by taking corrective actions. PMID- 24216549 TI - Uncommon lymphoepithelial cyst with sebaceous glands of the pancreas. AB - CONTEXT: Lymphoepithelial cysts with sebaceous glands of the pancreas are extremely rare, with only 7 cases, including this case, published in English literature. CASE REPORT: We herein present the case of a 67-year-old Asian man who underwent a resection of a lymphoepithelial cyst of the pancreas during the follow up care for lung cancer. Fourteen years previously he underwent a right lower lobectomy at the right segment nine for lung cancer. A 20 mm mass in the body of the pancreas was identified by CT scan 4 years ago, and the diagnosis was intraductal papillary mucinous neoplasm (IPMN) at that time. Over a 5-year period, this mass grew to 42 mm without dilatation of the main pancreatic duct. The preoperative evaluation, including endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), indicated a cystic neoplasm with suspicion of malignancy. Intraoperative frozen section revealed a squamous-lined cyst accompanied by sebaceous glands without any malignant findings. Following this pathological finding, resection of the cyst was performed. Consequently, microscopic examination revealed that it was a lymphoepithelial cyst with sebaceous glands of the pancreas. CONCLUSIONS: Pancreatic lymphoepithelial cysts can be cured by conservative resection, but if they are asymptomatic and are diagnosed before surgery, no treatment is necessary. To our knowledge, this is the first ever published case of a lymphoepithelial cyst with sebaceous glands of the pancreas, which was found during the follow up care for lung cancer. PMID- 24216550 TI - Laparoscopic distal pancreatectomy for multiple epithelial cysts in an intrapancreatic accessory spleen. A case report and review of literature. AB - CONTEXT: Accessory spleen is a congenital abnormality consisting of normal splenic tissue in ectopic sites that is found in approximately 10-15% of the general population. However, an intrapancreatic accessory spleen has seldom been reported and multiple epithelial cysts in the intrapancreatic accessory spleen are extremely rare. CASE REPORT: A 37-year-old woman with no clinical manifestations presented with two cystic lesions in the tail of the pancreas. The tumor markers CA 19-9 (251 U/mL) and SPAN-1 (38 U/mL) were increased. Computed tomography showed a multilocular cyst, 40 mm in size, and a unilocular cyst, 20 mm in size, in the tail of the pancreas and gallstones. The cystic component was hypointense on T1-weighted magnetic resonance images and hyperintense on T2 weighted magnetic resonance images. A laparoscopic distal pancreatectomy was performed with the presumptive diagnosis of a mucinous cystic neoplasm or an intraductal papillary mucinous neoplasm with gallstones. The pathological examination showed that the walls of the two cysts were covered with non keratinized stratified squamous epithelium, surrounded by normal splenic tissue. The final pathological diagnosis was two epithelial cysts originating from an intrapancreatic accessory spleen. CONCLUSIONS: Even though multiple masses were detected in the pancreatic tail, the possibility of epithelial cysts originating from an accessory spleen should be considered. Laparoscopic distal pancreatectomy might be a safe and effective procedure and provide good cosmetic result for a benign or low-grade malignant tumor in the pancreas. PMID- 24216551 TI - Solid and cystic papillary neoplasm of the pancreas in a 18-year-old female: a case report. AB - CONTEXT: Solid and cystic papillary neoplasm of the pancreas is an extremely rare neoplasm that mostly affects young females in the mean age of 25 years and accounts for about 0.2-2.7% of all pancreatic tumors. CASE REPORT: A 18-year-old female presented with progressively increasing mass in the left hypochondrium and epigastric regions and vague abdominal pain. There was no history of jaundice and vomiting. The mean diameter of the tumors was 17x24 cm. Preoperative core needle revealed solid and cystic papillary neoplasm. Distal pancreatectomy and splenectomy were performed. The patient did not receive adjuvant therapy and no tumor recurrence was detected in follow up. CONCLUSION: Solid and cystic papillary neoplasm may reach large dimensions with a benign behavior and is curable by surgical excision. Differential diagnosis from other tumors with aggressive behavior is therefore important. PMID- 24216552 TI - Kissing gastric ulcers causing acute pancreatitis and portal biliopathy: what's the link? AB - CONTEXT: Acute pancreatitis is often caused by acute alcoholic intoxication or biliary stone migration. Other etiologies are less frequent. CASE REPORT: We report an exceptional case of kissing ulcer as the cause of an acute pancreatitis due to the perforation of the posterior ulcus into the pancreas. More remarkable is the association of a left portal branch thrombosis and a portal biliopathy. CONCLUSION: We describe a case of acute pancreatitis of unusual origin, associated with an equally uncommon pathology which is portal cavernoma. A literature review is then exposed to try to ascertain if there is a connection between these two entities. PMID- 24216553 TI - Transpancreatic hepatomesenteric trunk complicating pancreaticoduodenectomy. AB - CONTEXT: Standard celiac and hepatic arterial anatomy occur in approximately 60% of the patients; for the remaining, multiple variations have been described. A thorough knowledge of these anomalies is important in order to avoid unnecessary complications. In this report we describe one of the rarest arterial anomalies, a hepatomesenteric trunk supplying the liver. We attempt to elucidate its implications pertaining to the safe performance of a pancreaticoduodenectomy. CASE REPORT: A 45-year-old male with a one-month duration painless progressive jaundice was evaluated and diagnosed as having a periampullary growth. Preoperative imaging did not suggest any arterial anomalies. Intraoperatively, the common hepatic artery was found to originate from the superior mesenteric artery. He underwent a pylorus preserving pancreaticoduodenectomy with a meticulous dissection and preservation of the aberrant hepatomesenteric trunk. His postoperative period was uneventful and is doing well on follow up. CONCLUSION: Variations in hepatic and celiac arterial anatomy are common, and may not get picked up on preoperative imaging. A high index of suspicion in every patient along with a precise knowledge of the normal anatomy and awareness of the aberrant anatomy is a sine qua non to the performance of a safe pancreaticoduodenectomy. PMID- 24216554 TI - Case report of pancreatic dermoid cyst: can fine needle aspiration make the diagnosis? AB - CONTEXT: Pancreatic dermoid cysts are rare, benign, germ cell tumors and part of the differential diagnosis for cystic neoplasms of the pancreas. CASE REPORT: A 35-year-old man presented with an incidentally discovered, 2 cm cystic pancreatic neoplasm of the pancreatic tail identified on CT scan. Endoscopic ultrasound (EUS) revealed a complex, honeycomb lesion. Fine needle aspiration (FNA) yielded a sample of whitish, necrotic material containing histiocytes, benign epithelial cells, and lymphocytes. After distal pancreatectomy and splenectomy was performed, histology revealed a cyst lined by stratified squamous epithelium with benign sebaceous units consistent with a pancreatic dermoid cysts. DISCUSSION: Although axial imaging reliably detects cystic neoplasms of the pancreas, diagnostic criteria for rare lesions are lacking; therefore alternative modalities such as EUS/FNA can be utilized. This case report highlights the EUS and FNA findings associated with pancreatic dermoid cysts. PMID- 24216555 TI - Squamoid cyst of pancreatic ducts: a challenging differential diagnosis among benign pancreatic cysts. AB - CONTEXT: In the last years, cystic pancreatic lesions are often detected when clinically silent, because of the wider use of diagnostic imaging techniques. First described by Othman in 2007, "squamoid cyst of pancreatic ducts" represents a cystic dilation of ducts, lined by non-keratinized squamous epithelium. We report the first case of squamoid cyst of pancreatic ducts in Italy. CASE REPORT: A 68-year-old woman presented a cystic lesion (4 cm) of the pancreatic tail as incidental finding at MRI. It had a thickened wall, no internal septa and no communication with the Wirsung duct were detected. A CT scan showed a lamellar calcification on its posterior wall. A 18F-FDG-PET was negative. Blood tests were normal, including CEA and CA 19-9. We performed a spleen-preserving distal pancreatectomy. Histology showed a unilocular cyst, with serous fluid and a fibrous wall, with multilayered epithelium without cytological atypias. Immunohistochemistry showed CK 7 positive and CK 5 negative. The patient is still alive and without disease after 42 months of follow-up. CONCLUSIONS: In the English literature only seven cases resected for this cyst type have been reported. No preoperative test can achieve a definitive diagnosis, so surgical resection remains the treatment of choice in order to exclude malignancy. However, after intraoperative frozen section, a limited pancreatic resection can be performed. PMID- 24216556 TI - Chin tremors associated with paroxetine in a patient with pancreatic adenocarcinoma. AB - CONTEXT: There have been many cases of medication-induced tremors. We report a patient who developed significant chin tremors after the administration of paroxetine. CASE REPORT: A 68-year-old Vietnamese female with a past medical history including GIST and pancreatic cancer status post Whipple procedure and six months of adjuvant chemotherapy with gemcitabine presented with symptoms of anxiety for which she was treated with paroxetine. Within 2 weeks she developed chin tremors which resolved after paroxetine was discontinued. CONCLUSIONS: To our knowledge, this is the first case report of a temporary chin tremor associated with paroxetine. The exact mechanism of this phenomenon is unclear. However, it has been suggested that movement disorders such as chin tremors may be related to elevated serotonin levels causing an inhibition of central dopamine. PMID- 24216557 TI - Laparoscopic distal pancreatectomy for a pancreatic lymphoepithelial cyst: case report and review of literature. AB - CONTEXT: Lymphoepithelial cysts of the pancreas are a rare disease of true pancreatic cysts, the cause of which is unknown. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. CASE REPORT: The present case report is a lymphoepithelial cyst of the pancreas that was resected laparoscopically. A 53-year-old man was incidentally found to have a cystic tumor in the tail of the pancreas after undergoing an abdominal ultrasound, which showed a 41x33 mm cystic mass in the pancreatic tail. He had no abdominal symptoms. Laparoscopic distal pancreatectomy and splenectomy were performed. Histologic examination revealed a lymphoepithelial cyst. CONCLUSION: Herein, we discuss the diagnostic difficulties and management decisions that face surgeons treating pancreatic cysts. PMID- 24216558 TI - Unusual foreign body of pancreas: surgical management. AB - CONTEXT: The foreign ingestion is common occurrence but migration to pancreas is rare entity. Most of foreign bodies pass spontaneously through the anus but about 1% can perforate the wall of stomach or duodenum to reach solid organ. Pancreatic foreign body can results in fatal complication. Pancreatic foreign body can be removed endoscopically or surgically. CASE REPORT: We are reporting a case of successful removal of pancreatic foreign body (sewing needle) by surgery. CONCLUSION: Pancreatic foreign body is a uncommon entity and surgical removal is warranted in majority of cases. PMID- 24216559 TI - Mucinous cystic neoplasm in heterotopic pancreas presenting as colonic polyp. AB - CONTEXT: Pancreatic heterotopia in itself is rare in the colon and to the best of our knowledge a neoplasm arising in a heterotopic tissue in the colon has not been reported. We herein report a pancreatic cystic neoplasm arising from heterotopic pancreatic tissue in colon. CASE REPORT: A 44-year-old lady presented with a history of lower abdominal colic, associated with mucoid loose stools 10 15 times/day. Fecal occult blood was positive on two occasions. On examination, a vague mass was palpable in the left upper quadrant of abdomen. Colonoscopy showed a polypoid growth at the splenic flexure of colon, which on biopsy was reported to be an inflammatory polyp. She underwent a laparoscopic converted to open left hemicolectomy. Post-operatively she developed a intra-abdominal collection which formed a controlled pancreatic fistula after percutaneous drainage. Histopathology revealed pancreatic heterotopia with pancreatic mucinous cystic neoplasm. CONCLUSION: Despite advances in patient care, preoperative diagnosis of heterotopic pancreas is difficult. PMID- 24216560 TI - Secondary varicocele caused by pancreatic pseudocyst obstructing testicular venous drainage. AB - A pseudocyst is a fluid/debris collection that occurs as a complication of pancreatitis. It can be symptomatic and cause compression of the surrounding structures. Our case report highlights a 29-year-old male who presented with secondary varicocele on left side caused by a huge pseudocyst seen to compress the left renal and testicular veins. PMID- 24216561 TI - Ototoxicity associated with oxaliplatin in a patient with pancreatic cancer. AB - CONTEXT: Oxaliplatin, a third-generation platinum derivative is commonly used for the treatment of colorectal cancer, pancreatic cancer, upper gastrointestinal cancer, hepatobiliary cancer, and ovarian cancer. Neurotoxicity is the dose limiting toxicity and ototoxicity is very rare, less than 1% of patients. CASE REPORT: We present a case of a female patient with locally advanced unresectable pancreatic cancer who developed hearing loss after receiving oxaliplatin and gemcitabine. The dose of oxaliplatin was reduced but continued due to clinical benefit and radiological response. DISCUSSION: To the best of our knowledge, this is the third case report of oxaliplatin-induced ototoxicity. Ototoxicity seems to be a rare complication of oxaliplatin therapy. Regardless of its rare occurrence, clinicians should be aware of this severe complication and be diligent in monitoring patients's clinical symptoms. PMID- 24216562 TI - Accuracy of CA 19-9 and radiologic imaging in detecting recurrence after resection for pancreatic cancer. PMID- 24216563 TI - Is bortezomib a rare cause of acute pancreatitis? PMID- 24216564 TI - Gastric ectopic pancreas: not always an innocent bystander. PMID- 24216565 TI - U.S. Food and Drug Administration approves paclitaxel protein-bound particles (Abraxane(r)) in combination with gemcitabine as first-line treatment of patients with metastatic pancreatic cancer. PMID- 24216566 TI - Comment on "Disruption of social approach by MK-801, amphetamine & fluoxetine in adolescent C57BL/6J mice"--by S. Moy et al. PMID- 24216567 TI - Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: a prospective cohort study using 7-day food diaries. AB - INTRODUCTION: Dietary fatty acids may be involved in the etiology of ulcerative colitis (UC). Arachidonic acid (AA), an n-6 polyunsaturated fatty acid, is a precursor of the proinflammatory cytokines prostaglandin E2 and leukotriene B4, and its metabolism is competitively inhibited by oleic acid (OA). This study aimed to prospectively investigate whether AA is positively and OA is negatively associated with incident UC development, using data from 7-day food diaries. METHODS: A total of 25 639 men and women, aged between 40 and 79 years, from Norfolk, UK, were recruited into the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort between 1993 and 1997. At baseline, participants completed 7-day food diaries, checked by nutritionists using a database containing 11 000 foods and 55 000 portion sizes. The cohort was monitored until June 2004 to identify participants who developed UC. Each patient was matched for age and sex with four controls, and conditional logistic regression was used to calculate adjusted odds ratios for AA and OA intakes, and UC association. RESULTS: Of the participants, 26 (58% men) developed incident UC (53% left sided) after a median follow-up time of 3.8 years (0.5-8.3 years). The highest AA tertile was positively associated with an odds ratio of 6.09 [95% confidence interval (CI) 1.05-35.23], with a trend across tertiles [odds ratio (OR) 2.43, 95% CI 1.06-5.61, P=0.04]. The highest tertile of OA intake was inversely associated with a 0.03 OR for UC (95% CI 0.002-0.56) and an inverse trend (OR 0.30, 95% CI 0.10-0.90, P=0.03). CONCLUSION: Dietary AA was positively and OA was inversely associated with UC development, with large effect sizes in a dose-dependent manner. This supports roles for measuring these nutrients in future etiological studies and modifying intake in future interventional studies in patients with established disease. PMID- 24216568 TI - Patient knowledge in inflammatory bowel disease: the Crohn's and Colitis Knowledge Score. AB - In the UK, key professional organizations have joined to provide inflammatory bowel disease (IBD) standards to be delivered by the NHS, highlighting the importance of patient education and support. The Crohn's and Colitis Knowledge Score (CCKNOW) is a validated multiple-choice questionnaire on the subject of IBD that is able to objectively quantify the level of patient knowledge. The aim of this study was to summarize the findings of the CCKNOW, in particular, the current level of patient knowledge and the implications clinically. Literature search was conducted using Medline, Google Scholar and the Cochrane Library, compiling results of studies using the CCKNOW to date. In the UK, a median score of 10 was achieved by participants with IBD in Leicestershire in 1999. Recent surveys in the Northwest and Pennine Trust achieved median scores of 9 and 7, respectively. Knowledge deficits regarding fertility and pregnancy were found, as seen in 1999. Studies in Canada and Iran achieved median scores of 13 and 4, respectively. Sri Lanka achieved a mean score of 6.86 (range 1-16). Higher CCKNOW scores were associated with the use of adaptive coping strategies. A significant positive link was found between patient knowledge and anxiety levels. There was no significant difference in CCKNOW scores between patients with the complication of colorectal cancer versus control populations. In the UK, patient knowledge of IBD may be no better than in 1999. The subjects of fertility and implications for pregnancy are particular areas of deficit. Further knowledge shortfalls may exist in the developing countries. Evidence suggests that improving knowledge may empower patients to use more adaptive coping strategies but may not be effective in reducing anxiety or the risk complications such as colorectal cancer. PMID- 24216569 TI - Herpes zoster in Crohn's disease during treatment with infliximab. AB - Infliximab is widely used in both inducing and maintaining remission of patients with Crohn's disease (CD). The efficacy of infliximab has been undoubtedly proven; however, various opportunistic infections have emerged. Herpes virus infections (being a type of opportunistic infection) in CD patients treated with infliximab alone with no other concomitant medications are, however, rare and have not aroused enough attention. Gastroenterologists have limited knowledge of the immunization status of patients with CD, and rarely do they take an adequate immunization history before immunosuppressive therapy. Here we report two herpes zoster (HZ) events in CD patients while using infliximab alone: in the first case, HZ occurred during the patient's 12th infusion for maintance therapy, and in the second case, HZ occurred during the patient's first course of infliximab after surgery for therapy of inducing remission. We hope to increase the gastroenterologists' awareness of this potential infection in CD patients during treatment with infliximab. PMID- 24216570 TI - A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care. AB - BACKGROUND: Reports suggest that gluten sensitivity (GS) exists in the absence of coeliac disease (CD). This clinical entity has been termed noncoeliac gluten sensitivity (NCGS). OBJECTIVES: To determine the population prevalence of self reported GS and referral characteristics to secondary care. PATIENTS AND METHODS: A UK population-based questionnaire screened for GS and related symptoms. Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive coeliac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1-3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD. Clinical comparisons were made between NCGS and CD. RESULTS: A total of 1002 adults in the population (female 55%, mean age 39 years). The self-reported prevalence for GS was 13% (female 79%, mean age 39.5 years, P<0.0001), with 3.7% consuming a gluten-free diet and 0.8% known to have a doctor diagnosis of CD. Individuals with GS had an increased prevalence of fulfilling the Rome III criteria for irritable bowel syndrome, in comparison with those without GS (20 vs. 3.89%, odds ratio 6.23, P<0.0001).In secondary care 200 GS patients (female 84%, mean age 39.6 years) were investigated, in whom 7% were found to have CD and 93% to have NCGS. All CD patients were human leucocyte antigen DQ2 or DQ8 positive compared with 53% of NCGS cases (P=0.0003). Nutritional deficiencies (P<=0.003), autoimmune disorders (23.1 vs. 9.7%, P=0.0001) and a lower mean BMI (23.7 vs. 25.8, P=0.001) were significantly associated with CD compared with NCGS. CONCLUSION: GS is commonly self-reported with symptoms suggesting an association with irritable bowel syndrome. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD. PMID- 24216571 TI - Birth-cohort patterns in Crohn's disease and ulcerative colitis. AB - AIM: To test the long-term time trends of mortality from inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), for the presence of birth-cohort phenomena. METHODS: We analyzed mortality data from the national statistical offices of Canada, England and Wales, Italy, the Netherlands, Switzerland, and the USA for the past 60-80 years. Age-specific rates of death were plotted against the period of death, as period-age contours, and against the period of birth, as cohort-age contours. RESULTS: In all six countries alike, the general time trends of IBD have been shaped by an underlying birth-cohort pattern. This pattern was also observed in the data of CD and UC analyzed separately. UC mortality increased in all generations born during the 19th century. It peaked among generations born shortly before the turn of the century and then decreased in all subsequent generations born throughout the 20th century. Compared with UC, the birth-cohort pattern of CD was delayed by 30-50 years. CONCLUSION: In addition to one risk factor responsible for the general occurrence of IBD and possibly UC alone, there exists at least one additional risk factor responsible for CD. Exposure to both separate risk factors must occur during early life. PMID- 24216572 TI - Hydrogen-atom-mediated electrochemistry. AB - Silicon dioxide thin films are widely used as dielectric layers in microelectronics and can also be engineered on silicon wafers. It seems counterintuitive that electrochemical reactions could occur on such an insulator without relying on tunnelling current. Here we report electrochemistry based on electron transfer through a thin insulating layer of thermally grown silicon dioxide on highly n-doped silicon. Under a negative electrical bias, protons in the silicon dioxide layer were reduced to hydrogen atoms, which served as electron mediators for electrochemical reduction. Palladium nanoparticles were preferentially formed on the dielectric layer and enabled another hydrogen-atom mediated electrochemistry, as their surfaces retained many electrogenerated hydrogen atoms to act as a 'hydrogen-atom reservoir' for subsequent electrochemical reduction. By harnessing the precisely controlled electrochemical generation of hydrogen atoms, palladium-copper nanocrystals were synthesized without any surfactant or stabilizer on the silicon dioxide layer. PMID- 24216573 TI - Statistical power of multilevel modelling in dental caries clinical trials: a simulation study. AB - Outcome data from dental caries clinical trials have a naturally hierarchical structure, with surfaces clustered within teeth, clustered within individuals. Data are often aggregated into the DMF index for each individual, losing tooth- and surface-specific information. If these data are to be analysed by tooth or surface, allowing exploration of effects of interventions on different teeth and surfaces, appropriate methods must be used to adjust for the clustered nature of the data. Multilevel modelling allows analysis of clustered data using individual observations without aggregating data, and has been little used in the field of dental caries. A simulation study was conducted to investigate the performance of multilevel modelling methods and standard caries increment analysis. Data sets were simulated from a three-level binomial distribution based on analysis of a caries clinical trial in Scottish adolescents, with varying sample sizes, treatment effects and random tooth level effects based on trials reported in Cochrane reviews of topical fluoride, and analysed to compare the power of multilevel models and traditional analysis. 40,500 data sets were simulated. Analysis showed that estimated power for the traditional caries increment method was similar to that for multilevel modelling, with more variation in smaller data sets. Multilevel modelling may not allow significant reductions in the number of participants required in a caries clinical trial, compared to the use of traditional analyses, but investigators interested in exploring the effect of their intervention in more detail may wish to consider the application of multilevel modelling to their clinical trial data. PMID- 24216574 TI - Sensitivity improvement of resonator integrated optic gyroscope by double electrode phase modulation. AB - In this paper, a novel method to improve the sensitivity of RIOGs is demonstrated by double-electrode phase modulation (DPM) technology. The scale factor of RIOGs with single-electrode phase modulation (SPM) and DPM are theoretically analyzed and calculated. The relationship between the slope rate in the linear region adjacent to the zero-offset point and the amplitudes of the triangle waveform with SPM and DPM are obtained; the RIOG's highest sensitivity appears when the triangle waveforms have amplitudes of 45.9 and 22.95 V, respectively. Compared with the SPM, the DPM shows great advantage in improving the RIOG scale factor, as well as its bias stability. Moreover, in measurements using the RIOG experimental setup, the scale factor is significantly increased from 1.49 to 2.76, which is coincident with the simulation result. The test results for long term bias stability demonstrate that the DPM has the advantage of improving the signal-to-noise ratio (SNR); significantly, the RIOG long-term bias stability is greatly improved from 0.61 to 0.49 deg/s, which is the best long-term stability result reported to date, to the best of our knowledge, for a waveguide-type integrated optical resonator (IOR). PMID- 24216575 TI - Dynamics of an all-optical atomic spin gyroscope. AB - We present the transfer function of an all-optical atomic spin gyroscope through a series of differential equations and validate the transfer function by experimental test. A transfer function is the basis for further control system design. We build the differential equations based on a complete set of Bloch equations describing the all-optical atomic spin gyroscope, and obtain the transfer function through application of the Laplace transformation to these differential equations. Moreover, we experimentally validate the transfer function in an all-optical Cs-Xe129 atomic spin gyroscope through a series of step responses. This transfer function is convenient for analysis of the form of control system required. Furthermore, it is available for the design of the control system specifically to improve the performance of all-optical atomic spin gyroscopes. PMID- 24216576 TI - Fabrication of channel waveguides in dye-doped polymer films by a beam-processing machine based on photo induced bleaching. AB - Irreversible changes in the refractive index of a dye-doped polymer film by photo induced bleaching were measured with a Mach-Zehnder interferometer. The decrease in the refractive index of the film for various laser powers and various radiation times has been investigated. A beam-processing machine with two simultaneous outputs has been designed to make use of this change in the refractive index to fabricate a channel waveguide. This method is simple and one step, and does not involve any solvent or mask; and also due to photobleaching, the pattern is not reversible. PMID- 24216577 TI - Ultimate efficiency of spectral beam combining by volume Bragg gratings. AB - Spectral beam combining (SBC) by volume Bragg gratings (VBGs) recorded in photo thermo-refractive (PTR) glass is a powerful tool for laser applications that require higher radiance than a single laser unit can achieve. The beam-combining factor (BCF) is introduced as a tool to compare various beam-combining methods and experiments. It describes the change of radiance provided by a beam-combining system but is not affected by the initial beam quality of the combined lasers. A method of optimization of VBGs providing the maximum efficiency of SBC has been described for an arbitrary number of beams. An experiment confirming the proposed modeling for a two-beam SBC system by a single VBG has demonstrated a total combined power of 301 W with a channel separation of 0.25 nm, combining efficiency of 97%, close to diffraction limited divergence with M(2)=1.18, BCF of 0.77, and spectral radiance of 770 TW/(sr.m(2).nm), the highest to date for SBC. PMID- 24216578 TI - Modeling angular-dependent spectral emissivity of snow and ice in the thermal infrared atmospheric window. AB - A model of angular-dependent emissivity spectra of snow and ice in the 8-14 MUm atmospheric window is constructed. Past field research revealed that snow emissivity varies depending on snow grain size and the exitance angle. Thermography images acquired in this study further revealed that not only welded snow particles such as sun crust, but also disaggregated particles such as granular snow and dendrite crystals exhibit high reflectivity on their crystal facets, even when the bulk snow surface exhibits blackbody-like behavior as a whole. The observed thermal emissive behaviors of snow particles suggest that emissivity of the bulk snow surface can be expressed by a weighted sum of two emissivity components: those of the specular and blackbody surfaces. Based on this assumption, a semi-empirical emissivity model was constructed; it is expressed by a linear combination of specular and blackbody surfaces' emissivities with a weighting parameter characterizing the specularity of the bulk surface. Emissivity spectra calculated using the model succeeded in reproducing the past in situ measured directional spectra of various snow types by employing a specific weighting parameter for each snow type. PMID- 24216579 TI - Tests and evaluation of a variable focus liquid lens for curvature wavefront sensors in astronomy. AB - Curvature wavefront sensors (WFSs), which obtain the wavefront aberrations from two defocused intensity images at each side of the pupil plane, have shown to be highly efficient for astronomical applications. We propose here an alternative defocusing mechanism for curvature sensors, based on an electrowetting-based variable focus liquid lens. Typically, the sampling rates of a WFS for active optics are of the order of 0.01 Hz, and the focus modulation can be done by simply moving the detector back and forth. On the other hand, adaptive optics may require speeds of up to several hundred hertz, and the modulation is then done by using a fast vibrating membrane mirror. We believe variable focus liquid lenses may be able to perform this focus modulation, reducing the overall size of the system and without the need of extra moving parts. We have done a full characterization of the Varioptic Arctic 416 liquid lens, and we have evaluated its potential performance in different curvature configurations. PMID- 24216580 TI - Immersed transparent microsphere magnifying sub-diffraction-limited objects. AB - The resolution of an optical microscope is restricted by the diffraction limit, which is approximately 200 nm for a white light source. We report that sub diffraction-limited objects can be resolved in immersion liquids using a microsphere optical nanoscopy (MONS) technique. Image magnifications and resolutions were obtained experimentally and compared in different immersion liquids. We show that a 100 MUm diameter barium titanate (BaTiO(3)) glass microsphere combined with a standard optical microscope can image sub-diffraction limited objects with halogen light in three different media: water, 40% sugar solution, and microscope immersion oil. In this paper, the super-resolution imaging performance has been described with the three immersion liquid types and the mechanisms are discussed with Mie theory calculation in the field of a Poynting vector. PMID- 24216581 TI - Design of optical systems using derivatives of rays: derivatives of variable vector of spherical boundary surfaces with respect to system variable vector. AB - A computational scheme based on differential geometry was proposed in a previous study [Appl. Opt.52, 4151 (2013)] for determining the first- and second-order derivative matrices of a skew ray reflected/refracted at a flat boundary surface. The present study extends this methodology to the case of a skew ray reflected/refracted at a spherical boundary surface. The validity of the proposed approach is demonstrated using two retro-reflectors for illustration purposes. The results show that the proposed method provides an effective means of determining the search direction required to minimize the merit function during the optimization stage of the optical system design process. PMID- 24216583 TI - Iterative method for optimal design of flat-spectral-response arrayed waveguide gratings. AB - A novel iterative projection-type optimal design algorithm of arrayed waveguide gratings (AWGs) with a flat spectral response is proposed based on the Fourier optics model of AWG. The enhancement of the spectral-response flatness of the AWG is demonstrated, with an analysis on the trade-off relationship between band flatness and crosstalk. PMID- 24216582 TI - Embedded optical waveguides fabricated in SF10 glass by low-repetition-rate ultrafast laser. AB - Symmetric embedded waveguides were fabricated in heavy metal oxide SF10 glass using slit-shaped infrared femtosecond laser writing in the low-repetition frequency regime. The impact of the writing parameters on the waveguide formation in the transverse writing scheme was systemically studied. Results indicate that efficient waveguides can be inscribed in a wide parameter space ranging from 500 fs to 1.5 ps pulse duration, 0.7-4.2 MUJ pulse energy, and 5 MUm/s to 640 MUm/s scan speed and pointing out the robustness of the photoinscription process. The refractive index profile reconstructed from the measured near field pattern goes up to 10(-3). In addition, propagation losses of the waveguides are tolerable, with the lowest propagation loss estimated at 0.7 dB/cm. With a 5 MUm/s scan speed and 3.5 MUJ pulse energy in a high-dose regime, few-mode guiding was achieved in the waveguide at 800 nm signal injection wavelength. This is due to a combination of increased refractive index in the core of the trace and the appearance of a depressed cladding. PMID- 24216584 TI - Stable and tunable single frequency Nd:GSAG laser around 943 nm. AB - Stable single frequency output around 943 nm was obtained from a quasi-continuous wave (qcw) diode-pumped, Q-switched Nd:GSAG laser. The Q-switched Nd:GSAG laser was injection seeded with a single mode laser diode. Its frequency was stabilized by an active-control loop specially designed for a strong qcw pump. The spectral linewidth of the Nd:GASG laser was 41 MHz and the frequency stability was 10 MHz. The single-frequency-pulsed laser generated 32 mJ pulse energy at 10 Hz repetition rate. When the repetition rate was increased to 100 Hz, 5.6 mJ pulse energy was obtained by a thermal dynamic stable resonator. By tuning the seed laser, the wavelength of the pulsed Nd:GASG laser can be continuously varied from 942.1 to 943.1 nm. PMID- 24216585 TI - Method of misalignment aberrations removal in null test of cylindrical surface. AB - The removal of misalignment aberrations is a key problem in the null test of cylindrical surfaces. Although the quadratic polynomial with two variables and the orthogonal Chebyshev polynomials have been used to separate the misalignment aberrations from the extracted phase data, there is no physical meaning corresponding to the polynomials coefficients. Additionally, the Runge phenomenon may occur when the high-order polynomials are employed. In this paper, all the possible aberrations caused by the adjustment errors were analyzed. Based on the first-order approximate principle, the mathematical models, which describe the relationship between the misalignment aberrations and the possible adjustment errors, were deduced. With these mathematical expressions, all the possible adjustment errors can be estimated by using the least-squares fitting algorithm, and then the genuine surface deviations can be obtained by subtracting the misalignment aberrations from the extracted phase data. Computer simulations and experiments have been conducted to demonstrate the validity and feasibility, which show more than 96% misalignment aberrations can be removed. Compared with the existing methods, the proposed model provides a feasible way to estimate adjustment errors with better accuracy. PMID- 24216586 TI - Noninvasive quantification of postocclusive reactive hyperemia in mouse thigh muscle by near-infrared diffuse correlation spectroscopy. AB - Many vasculature-related diseases affecting skeletal muscle function have been studied in mouse models. Noninvasive quantification of muscle blood flow responses during postocclusive reactive hyperemia (PORH) is often used to evaluate vascular function in human skeletal muscles. However, blood flow measurements during PORH in small skeletal muscles of mice are rare due to the lack of appropriate technologies coupled with the challenge of measurement setup resulting from the lack of large enough test sites. In this study, we explored adapting diffuse correlation spectroscopy (DCS) for noninvasive measurement of the relative changes of blood flow (rBF) in mouse thigh muscles during PORH. A small fiber-optic probe was designed and glued on the mouse thigh to reduce the motion artifact induced by the occlusion procedure. Arterial occlusion was created by tying a polyvinyl chloride (PVC) tube around the mouse thigh while the muscle rBF was continuously monitored by DCS to ensure the success of the occlusion. After 5 min, the occlusion was rapidly released by severing the PVC tube using a cautery pen. Typical rBF responses during PORH were observed in all mice (n=7), which are consistent with those observed by arterial-spin-labeled magnetic resonance imaging (ASL-MRI) as reported in the literature. On average, rBF values from DCS during occlusion were lower than 10% (3.1+/-2.2%) of the baseline values (assigning 100%), indicating the success of arterial occlusion in all mice. Peak values of rBF during PORH measured by the DCS (357.6+/-36.3%) and ASL-MRI (387.5+/-150.0%) were also similar whereas the values of time-to-peak (the time duration from the end of occlusion to the peak rBF) were quite different (112.6+/-35.0 s versus 48.0+/-27.0 s). Simultaneous measurements by these two techniques are needed to identify the factors that may cause such discrepancy. This study highlights the utility of DCS technology to quantitatively evaluate tissue blood flow responses during PORH in mouse skeletal muscles. DCS holds promise as valuable tool to assess blood flow regulation in mouse models with a variety of vascular diseases (e.g., hypercholesterolemia, diabetes, peripheral artery disease). PMID- 24216588 TI - Supercontinuum generation in dispersion-managed tapered-rib waveguide. AB - We have designed a tapered-rib waveguide and numerically studied the generation of supercontinuum using such waveguides. The Air-SF57 glass-SiO(2) waveguide is 3 cm long, with a varying etched depth to manage the total dispersion. Numerical simulations are conducted for input pulses at a wavelength of 1.55 MUm with a width of 150 fs and peak power of 5 kW. The proposed waveguide geometry greatly broadens the output spectrum, extending from ~1 to ~6 MUm, caused by the continuous modification of the phase-matching condition for the generated waves. PMID- 24216587 TI - High-peak-power, single-frequency, single-mode, linearly polarized, nanosecond all-fiber laser based on self-phase modulation compensation. AB - We demonstrated a high-peak-power, single-frequency, single-mode, linearly polarized, nanosecond all-fiber laser in master oscillator power amplifier configuration. The pulsed seed was generated by modulating a single-frequency continuous wave laser at 1064 nm. The short pulse width (~3.2 ns) of the pulsed seed prevented the onset of stimulated Brillouin scattering in the 10 MUm-core single-transverse-mode polarization-maintaining ytterbium-doped fiber of the main amplifier. In order to compensate self-phase modulation-induced spectral broadening, a phase modulator was employed to control the phase of the pulsed seed, and the linewidth of the output pulses were reduced from ~1.22 GHz to ~185 MHz at the peak power of 1.47 kW. PMID- 24216589 TI - Lasers for coherent optical satellite links with large dynamics. AB - We present the experimental realization of a laser system for ground-to-satellite optical Doppler ranging at the atmospheric turbulence limit. Such a system needs to display good frequency stability (a few parts in 10-14) while allowing large and well-controlled frequency sweeps of +/-12 GHz at rates exceeding 100 MHz/s. Furthermore it needs to be sufficiently compact and robust for transportation to different astronomical observation sites, where it is to be interfaced with satellite ranging telescopes. We demonstrate that our system fulfills those requirements and should therefore allow operation of ground to low Earth orbit satellite coherent optical links limited only by atmospheric turbulence. PMID- 24216590 TI - Femtosecond electron-lattice thermalization dynamics in a gold film probed by pulsed surface plasmon resonance. AB - The dynamics of electronic excitations and their relaxation in a gold film is studied on the femtosecond time scale with a pump-probe technique. For the pump beam we use pulses with wavelengths centered at 800 nm, 400 nm or both. The surface plasmon resonance (SPR) in Kretschmann's configuration is used as a sensitive and fast-response probe of the dynamics of the dielectric properties of the gold film. The quantity that is monitored is the intensity of the reflected light at an incidence angle close to the SPR. With changes of the dielectric properties induced by the pump beam and during subsequent relaxation, the amount of the reflected light of the probe beam, sent with a variable delay, also changes, thus providing information on the temporal characteristics of the thermalization process. Special features of SPR probing with short pulses are also accounted for in this work. The thermalization of the electronic subsystem and energy transfer to the lattice are discussed in connection with the two temperature relaxation model that takes into account temperature dependences of the electronic heat capacity and the electron-phonon coupling. PMID- 24216591 TI - Three-dimensional measurement of object surfaces with complex shape and color distribution based on projection of color fringe patterns. AB - A challenging issue associated with three-dimensional (3D) fringe patterns profilometry (FPP) is the unwrapping of phase maps resulting from color object surfaces. This paper proposes a new color-projection-based 3D FPP, making use of the three primary color channels [i.e., red, green, and blue (RGB)] associated with digital projectors. One channel (e.g., red) is used for projecting sinusoidal fringes required by phase shift profilometry (PSP); the other two channels are employed for generating binary stripe patterns. In order to achieve reliable phase unwrapping, each fringe of the sinusoidal patterns is identified by a unique binary sequence. These sequences are then encoded by a channel encoding scheme used in the area of communication. The encoded sequences are embedded in the binary coding stripe images, which are projected together with the sinusoidal patterns. The three image patterns are reflected by the object surface and captured by an RGB 3-CCD camera. The reflected sinusoidal patterns are employed to yield a wrapped phase map, and the binary stripe patterns are used to retrieve the encoded sequences, which are then decoded to yield the original binary sequences for phase unwrapping. Compared with existing color encoded algorithms, the proposed approach uses binary codes instead of fringe color to identify the fringes, which are less sensitive to the disturbances caused by object surface color and illumination noises. Furthermore, use of the channel-coding scheme provides extra resistance to the disturbances caused by object surface color and illumination noises. Experimental results are presented to confirm the effectiveness of the proposed technique. PMID- 24216592 TI - Finite element method analysis of band gap and transmission of two-dimensional metallic photonic crystals at terahertz frequencies. AB - Photonic band gap and transmission characteristics of 2D metallic photonic crystals at THz frequencies have been investigated using finite element method (FEM). Photonic crystals composed of metallic rods in air, in square and triangular lattice arrangements, are considered for transverse electric and transverse magnetic polarizations. The modes and band gap characteristics of metallic photonic crystal structure are investigated by solving the eigenvalue problem over a unit cell of the lattice using periodic boundary conditions. A photonic band gap diagram of dielectric photonic crystal in square lattice array is also considered and compared with well-known plane wave expansion results verifying our FEM approach. The photonic band gap designs for both dielectric and metallic photonic crystals are consistent with previous studies obtained by different methods. Perfect match is obtained between photonic band gap diagrams and transmission spectra of corresponding lattice structure. PMID- 24216593 TI - Improved CCT uniformity of white LED using remote phosphor with patterned sapphire substrate. AB - The light distribution of a light-emitting diode (LED), using remote phosphor with a patterned sapphire substrate, is evaluated in this study. Three kinds of substrates of the remote phosphors, including planar sapphire (PS), partially patterned sapphire (PPS), and fully patterned sapphire (FPS) are prepared. The LED with the remote phosphor of FPS delivers much better uniformity of the correlated color temperature (CCT) in a far-field pattern than the CCT obtained in the cases of PS and PPS. The results are majorly attributed to the improvement in the scattering ability of the blue light in the FPS; thereby increasing the excitation of the phosphor particles in comparison to the ability of the device assembled with the remote phosphor of PS or PPS. PMID- 24216594 TI - Terahertz quantitatively distinguishing gasoline mixtures using multiparameter combined analysis. AB - Refined oil mixtures can be quantified using terahertz-absorption-coefficient spectra and dualistic linear regression fitting. However, when this method was used to quantify mixtures of 90# and 97# gasolines, the absolute error between the real and fitted value was large (25%), and this was due to the component similarity between 90# and 97# gasolines. To solve this problem, the present research addresses the possibility of developing a method that would allow direct, simple, and accurate determination of the 97# gasoline content in gasoline mixtures using a terahertz time-domain pulse coupled to a multiparameter combined analysis. The multiparameter represents the time delay and amplitude of the first transmission dip and peak in the time-domain pulse. The relationship between these four parameters and the 97# gasoline content in gasoline mixtures was thoroughly investigated, and four distinct calibration models for quantifying gasoline mixtures were built using least square fitting. To enable the development of an informative and accurate calibration model, the four individual models were given proper weights and combined. The weight was determined by the cosine-optimal method, which aimed to determine the most proper weight under the condition of the cosine of the angle between the fitted content vector and the real content vector that reaches the maximum. This method allows the determination of 97# gasoline content in gasoline mixtures with a low absolute error (6%), resulting in predictions that are more accurate and precise than those obtained by the terahertz-absorption-coefficient spectra and dualistic linear regression fitting. PMID- 24216595 TI - Optical analysis of a curved-slats fixed-mirror solar concentrator by a forward ray-tracing procedure. AB - Fixed-mirror solar concentrators (FMSCs) use a static reflector and a moving receiver. They are easily installable on building roofs. However, for high concentration factors, several flat mirrors would be needed. If curved mirrors are used instead, high-concentration levels can be achieved, and such a solar concentrator is called a curved-slats fixed-mirror solar concentrator (CSFMSC), on which little information is available. Herein, a methodology is proposed to characterize the CSFMSC using 3D ray-tracing tools. The CSFMSC shows better optical characteristics than the FMSC, as it needs fewer reflector segments for achieving the same concentration and optical efficiency. PMID- 24216596 TI - Triangular-range-intensity profile spatial-correlation method for 3D super resolution range-gated imaging. AB - We present a triangular-range-intensity profile (RIP) spatial-correlation method for 3D range-gated imaging with a depth of super resolution. In this method, spatial sampling volumes with triangular-RIPs are established by matching laser pulse width and sensor gate time, and then depth information collapsed in gate images can be reconstructed by spatial correlation of overlapped gate images corresponding to sampling volumes. Compared with super-resolution depth mapping under trapezoidal-RIPs, range accuracy and precision are improved, and a large range fluctuation due to noise disturbance is smoothed by noise suppression under triangular-RIPs. In this paper, a proof experiment is demonstrated with a range precision 2.5 times better than that obtained under trapezoidal-RIPs. PMID- 24216597 TI - What is the 'self' in chronic disease self-management? PMID- 24216598 TI - Foot massage versus quiet presence on agitation and mood in people with dementia: a randomised controlled trial. AB - BACKGROUND: There is increasing interest in using complementary and alternative treatments to manage behavioural and psychological symptoms of dementia such as agitation, aggression and depressed mood. OBJECTIVE: To compare the effect of foot massage (intervention) and quiet presence (control) on agitation and mood in people with dementia. DESIGN: A randomised controlled trial using a within subjects, crossover design. SETTINGS: Five long-term care facilities in Brisbane, Australia. The primary outcome was the Cohen-Mansfield Agitation Inventory (CMAI) and the secondary outcome was the Observed Emotion Rating Scale (OERS). The screening and data collection research assistants, families, and care staff were blinded to participant allocation. PARTICIPANTS: Participants of the study were 55 long-term care residents aged 74-103 years (mean age 86.5), with moderate to severe dementia and a history of agitated behaviour according to the Pittsburgh Agitation Scale. A computer-program randomised participants to 10-min foot massage (intervention) or quiet presence (control), every weekday for 3 weeks. RESULTS: A carry-over effect was identified in the data, and so the data was treated as a parallel groups RCT. The mean total CMAI increased in both groups (reflecting an increase in agitation) with this increase greater in the quiet presence group than the foot massage group (p=0.03). There was a trend towards a difference on OERS General Alertness, with a positive change in alertness for participants in the foot massage group (indicating reduced alertness) and a negative change for participants in the quiet presence group (indicating increased alertness) (F(1,51)=3.88, p=0.05, partial eta(2)=0.07). CONCLUSIONS: The findings highlight the need for further research on the specific conditions under which massage might promote relaxation and improve mood for people with dementia. The unfamiliar research assistants and variations in usual activity may have contributed to the increase in agitation and this needs further research. TRIAL REGISTRATION: ACTRN12612000658819. PMID- 24216599 TI - The meaning of emotion work to student nurses: a Heideggerian analysis. AB - BACKGROUND: Providing patients with emotional support can be challenging to student nurses, as it is seen as a less tangible aspect of care when compared to other acts of caring. OBJECTIVES: The underpinning objective of this study was to explore the meaning of emotional relationships between pre-registration nursing students and patients admitted to a clinical setting in the United Kingdom. DESIGN: Using an interpretive phenomenological approach data were collected using in depth unstructured interviews, with nine purposively recruited pre registration student nurses at a University in the United Kingdom. RESULTS: The structure of emotion work for these nurses, was found to consist of three constituents; (a) the need for an emotional "balance;" (b) feeling the need to cry; (c) feeling the need to talk. We portray this phenomenon as "emotional nurse being" using Heideggerian hermeneutic phenomenology. CONCLUSIONS: The insights gained from this study could be used to understand and support pre-registration student nurses in this aspect of their practice. PMID- 24216600 TI - Corrected VEGF levels based on platelet count should be calculated. Concerning the article by B.M. Levesque et al.: Low urine vascular endothelial growth factor levels are associated with mechanical ventilation, bronchopulmonary dysplasia and retinopathy of prematurity [Neonatology 2013;104:56-64]. PMID- 24216601 TI - Mass-density compensation can improve the performance of a range of different detectors under non-equilibrium conditions. AB - Dosimeters often consist of several components whose mass densities differ substantially from water. These components cause small-field correction factors to vary significantly as lateral electronic equilibrium breaks down. Even amongst instruments designed for small-field dosimetry, inter-detector variation in the correction factors associated with very small (~0.5 cm) fields can amount to tens of per cent. For a given dosimeter, small-field correction factors vary not only with field size but also with detector azimuthal angle and position within the field. Furthermore the accurate determination of these factors typically requires time-intensive Monte Carlo simulations. Thus, if achievable, 'correction factor free' small-field dosimetry would be highly desirable. This study demonstrates that a new generation of mass-density compensated detectors could take us towards this goal. Using a 6 MV beam model, it shows that 'mass-density compensation' can be utilized to improve the performance of a range of different detectors under small-field conditions. Non-sensitive material of appropriate mass-density is incorporated into detector designs in order to make the instruments behave as if consisting only of water. The dosimeter perturbative effects are then reduced to those associated with volume averaging. An even better solution-which modifies detectors to obtain profiles that look like those measured by a point-like water structure-is also considered. Provided that adequate sensitivity can be achieved for a small measurement volume, this study shows that it may be possible to use mass-density compensation (and Monte Carlo-driven design) to produce a solid state dosimeter/ionization chamber with a near-perfect non-equilibrium response. PMID- 24216602 TI - Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. AB - BACKGROUND/AIMS: Multiple myeloma (MM) is a hematological cancer associated with increased clonal malignant plasma cells. Growth differentiation factor 15 (GDF 15) is a protein that is highly expressed in the bone marrow mesenchymal stem cells of patients with MM. This study investigated whether the clinical stage of the disease, treatment response and survival are affected by pretreatment serum GDF 15 levels. METHODS: Serum GDF 15 levels were measured in 35 newly diagnosed MM patients and 27 healthy controls. The correlation between serum GDF 15 levels and various clinical and laboratory parameters was analyzed. RESULTS: The study demonstrated significantly higher levels of GDF 15 in MM patients. There was a negative correlation between GDF 15 levels, hemoglobin and albumin levels, and a positive correlation between GDF 15 levels, CRP, creatinine, beta-2-microglobulin and stage. GDF 15 levels were lower in patients who could receive autologous stem cell transplantation compared to other groups, representing a statistically significant difference. However, in the survival analyses, GDF 15 level did not have an impact on survival. CONCLUSION: High serum levels of GDF 15 may indicate a poor treatment response. Our study supports the prognostic value of GDF 15 in MM. PMID- 24216603 TI - Three-dimensional accuracy of ECOG strip electrode localization using coregistration of preoperative MRI and intraoperative fluoroscopy. AB - BACKGROUND/AIMS: Algorithms that estimate implanted cortical strip electrode coordinates using postoperative skull X-ray coregistration with preoperative magnetic resonance imaging (MRI) have been proposed. However, when cortical strip electrodes are inserted for temporary use and removed prior to closure, intraoperative imaging - either fluoroscopy or computed tomography (CT) - must be substituted. OBJECTIVES: To measure the accuracy of temporarily inserted subdural strip electrode coordinates using intraoperative fluoroscopic coregistration with preoperative MRI compared to intraoperative CT coregistration with preoperative MRI. METHODS: In 5 patients undergoing movement disorder surgery, preoperative MRI was used to generate a three-dimensional cortical surface manually scaled to fit an intraoperative skull fluorogram with an in situ six-contact subdural electrode strip. Individual contact coordinates were estimated using subjacent gyral and sulcal patterns. Estimated coordinates were compared to reference coordinates obtained by preoperative MRI coregistration with intraoperative CT in the same patients. RESULTS: Mean electrode coordinate distances between estimated and reference locations were 6.0 +/- 0.8 (x-axis, mediolateral), 3.3 +/- 0.5 (y axis, anterior-posterior) and 4.0 +/- 0.5 mm (z-axis, superior-inferior; n = 30). CONCLUSIONS: Localization of temporarily inserted subdural electrodes can be accomplished using preoperative MRI and intraoperative fluoroscopy. The accuracy of this approach is verified by preoperative MRI and intraoperative CT coregistration in the same patients. PMID- 24216604 TI - After the introduction into the national newborn screening program: who is receiving genetic counseling for hemoglobinopathies in the Netherlands? AB - OBJECTIVE: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, beta-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated with severe conditions in homozygote or compound heterozygote forms are identified yearly. Thus far, approximately 60 patients and 800 healthy sickle cell (HbS) carriers are reported each year among 180,000 newborns. Results are sent to the general practitioner with the recommendation to inform and diagnose both parents of the healthy carriers to exclude genetic risk, while patients and their parents are referred directly to a pediatrician. This study was performed to determine how often parents of identified carriers and affected newborns are seen in genetic centers for counseling. METHODS: In this retrospective study, we collected anonymized data from 7 of the 8 Dutch clinical genetic centers from January 1, 2007, until December 31, 2010. RESULTS: After an initial general increase in total counseling intakes, a decline was noticed in the third year, while the requests for prenatal diagnoses remained relatively stable. In 2007 and 2013, genetic counselors were asked for self-reported knowledge. They found hemoglobinopathy counseling complex, but by 2013, they indicated they had acquired sufficient knowledge on most hemoglobinopathy aspects. CONCLUSION: We could not observe a significant increase in genetic counseling for hemoglobinopathy after its introduction into newborn screening. Although 120 HbS carriers and 60 patients are expected to be born from couples at risk annually, only 33 at risk couples out of 540 families of diagnosed newborns received optimal care and information at a genetics center in 4 years. PMID- 24216606 TI - A solitary fibrous tumour of the eyelid. AB - OBJECTIVE: To report a case of palpebral solitary fibrous tumour (SFT). CLINICAL PRESENTATION AND INTERVENTION: An elderly man presented with a slow-growing painless mass in the lower conjunctival fornix in the left eye. The lesion was excised and it measured 0.9 cm in maximum diameter. The microscopic features were characteristic of a benign SFT, with immunohistochemical reactivity for vimentin, CD34 and Bcl-2 protein. Nuclear staining for progesterone receptor was also observed. CONCLUSION: This tumour displayed a benign course, with no recurrence after excision. CD34 immunohistochemistry proved to be a useful adjunct to the microscopic diagnosis. PMID- 24216607 TI - Oligomers based on weak hydrogen bond networks: a rotational study of the tetramer of difluoromethane. AB - We report the rotational spectrum of one conformer of the tetramer of difluoromethane (CH2F2)4 (the first pure rotational spectrum of a tetramer of an asymmetric rotor), and describe the network of weak hydrogen bonds which connect the four subunits. PMID- 24216608 TI - Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and cancer tissues. AB - Syncytin-1 is a human endogenous retroviral envelope gene (HERVW1) product specifically expressed in placental trophoblasts. By mediating the formation of syncytiotrophoblasts through cell-cell fusion, syncytin-1 plays a critical role for the placental barrier, endocrine and exchange functions. During pregnancy, syncytin-1 expression is dynamically regulated by various pathophysiological factors and pathways. This review summarizes and examines published data on epigenetic and non-epigenetic regulation of syncytin-1 gene expression, with a focus on the changes of syncytin-1 DNA methylation and expression in placental trophoblasts under preeclamptic and hypoxic conditions. The functions of syncytiotrophoblasts, the fusogenic and non-fusogenic activities of syncytin-1, and aberrant activation of syncytin-1 expression in cancer cells are also discussed. New findings on the epigenetic regulation of syncytin-1 in placentas from monozygotic/dichorionic discordant twins are analyzed. The close correlation among changes of DNMTs expression, syncytin-1 gene methylation, and syncytin-1 mRNA levels, in placentas associated with discordant fetal growth indicated a dynamic nature of syncytin-1 regulation. PMID- 24216609 TI - Increased activity of mitogen activated protein kinase pathway in flotillin-2 knockout mouse model. AB - Flotillins are highly conserved and widely spread proteins that function in receptor tyrosine kinase signaling and membrane trafficking processes. Flotillin 1 and flotillin-2 have been shown to form both homo- and hetero-oligomers, and their cellular localization changes during signaling. Increased expression of flotillins has been detected in several types of cancer and shown to correlate with poor survival. Consistently, flotillin-2 knockout mice show a reduced formation of metastases in a breast cancer animal model. Our recent data have shown that flotillin-1 depletion results in diminished activation of the epidermal growth factor receptor and impairs its downstream signaling towards the mitogen activated protein kinases and the respective transcriptional response. Here we show that genetic ablation of flotillin-2 in a mouse model or its knockdown in cultured cells increases extracellular signal regulated kinase (ERK) activation. Furthermore, the downstream transcriptional targets of ERK and p53 are upregulated at both mRNA and protein levels. These data suggest that opposite effects are obtained upon ablation of one of the two flotillins, with flotillin-2 knockout/knockdown enhancing and flotillin-1 knockdown inhibiting ERK signaling. Due to their overexpression in cancers, flotillins may be considered as cancer therapy targets. However, our findings suggest that care needs to be taken when interfering with flotillin function, as undesired effects such as deregulation of growth-associated genes may emerge in certain cell types. PMID- 24216610 TI - Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance. AB - Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact are not understood. Here we delineate how Akt and Rac1 pathways signal to increase glucose transport independently of each other and are simultaneously downregulated in insulin resistant muscle. Pharmacological inhibition of Rac1 and Akt signaling was used to determine the contribution of each pathway to insulin stimulated glucose uptake in mouse muscles. The actin filament-depolymerizing agent LatrunculinB was combined with pharmacological inhibition of Rac1 or Akt, to examine whether either pathway mediates its effect via the actin cytoskeleton. Akt and Rac1 signaling were investigated under each condition, as well as upon Akt2 knockout and in ob/ob mice, to uncover whether Akt and Rac1 signaling are independent and whether they are affected by genetically-induced insulin resistance. While individual inhibition of Rac1 or Akt partially decreased insulin-stimulated glucose transport by ~40% and ~60%, respectively, their simultaneous inhibition completely blocked insulin-stimulated glucose transport. LatrunculinB plus Akt inhibition blocked insulin-stimulated glucose uptake, while LatrunculinB had no additive effect on Rac1 inhibition. In muscles from severely insulin-resistant ob/ob mice, Rac1 and Akt signaling were severely dysregulated and the increment in response to insulin reduced by 100% and 90%, respectively. These findings suggest that Rac1 and Akt regulate insulin-stimulated glucose uptake via distinct parallel pathways, and that insulin-induced Rac1 and Akt signaling are both dysfunctional in insulin resistant muscle. There may thus be multiple treatment targets for improving insulin sensitivity in muscle. PMID- 24216611 TI - MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX. AB - The poor prognosis of invasive ductal adenocarcinoma of the pancreas is mainly due to its resistance against therapeutic agents. The molecular mechanism by which morbidity enhances cell survival has been extensively studied, but radical improvements in the therapeutic strategy have not yet been achieved. Recent reports have indicated the substantial contribution of miRNA in multiple cell functions by comprehensively targeting clusters of genes. We identified several miRNAs highly expressed in invasive ductal adenocarcinoma in our previous study, and clarified their contribution to the epithelial-mesenchymal transition. Among the differentially expressed miRNAs, miR-365 was highly expressed in invasive ductal adenocarcinoma, whose functional role has not been reported. In the current study, we found that miR-365 induced gemcitabine resistance in pancreatic cancer cells. MiR-365 directly targeted adaptor protein Src Homology 2 Domain Containing 1 (SHC1) and apoptosis-promoting protein BAX. The siRNA-based knockdown of SHC1 and BAX increased gemcitabine resistance, indicating the miR 365/SHC1/BAX axis influences the survival of pancreatic cancer cells. In addition, miR-365 up-regulated cancer-promoting molecules such as Inhibitor of DNA binding 2 and S100P, suggesting the existence of cross-talk with other cancer promoting signals. MiR-365 could exert orchestrated effects on pancreatic cancer cell survival. PMID- 24216612 TI - Role of extracellular matrix and YAP/TAZ in cell fate determination. AB - The mechanical signals transduced from cellular microenvironment can regulate cell shape and affect cell fate determination. However, how these mechanical signals are transduced to regulate biological processes of cells has remained elusive. Recent studies had elucidated a novel mechanism through which the interactions between mechanical signals from extracellular matrix and cell behavior regulation converged on the function of core components in Hippo signaling pathway, including YAP and TAZ in mammals. Moreover, several very recent studies have found a new crosstalk between Wnt and Hippo signaling in the regulation of cell fate determination. Such mechanism may explain how mechanical signals from microenvironment can regulate cell behavior and determine cell fate. PMID- 24216613 TI - Do Obsessions and Compulsions Play a Role in Social Anxiety Disorder? PMID- 24216614 TI - X-ray micro-beam characterization of lattice rotations and distortions due to an individual dislocation. AB - Understanding and controlling the behaviour of dislocations is crucial for a wide range of applications, from nano-electronics and solar cells to structural engineering alloys. Quantitative X-ray diffraction measurements of the strain fields due to individual dislocations, particularly in the bulk, however, have thus far remained elusive. Here we report the first characterization of a single dislocation in a freestanding GaAs/In0.2Ga0.8As/GaAs membrane by synchrotron X ray micro-beam Laue diffraction. Our experimental X-ray data agrees closely with textbook anisotropic elasticity solutions for dislocations, providing one of few experimental validations of this fundamental theory. On the basis of the experimental uncertainty in our measurements, we predict the X-ray beam size required for three-dimensional measurements of lattice strains and rotations due to individual dislocations in the material bulk. These findings have important implications for the in situ study of dislocation structure formation, self organization and evolution in the bulk. PMID- 24216615 TI - An administrative data algorithm to identify traumatic spinal cord injured patients: a validation study. AB - OBJECTIVE: To assess the validity of different administrative data sources available for the identification of traumatic spinal cord injured (TSCI) patients. STUDY DESIGN: Retrospective validation study. SETTING: Ontario, Canada. PARTICIPANTS: Adult patients seen in tertiary outpatient spinal cord rehabilitation clinics after 1 April 2002. OUTCOME MEASURES: Sensitivity, specificity, positive and negative predicative values of diagnostic ICD10 codes from Canadian Institutes of Health Discharge Abstracts (CIHI-DAD), Rehabilitation Coding Groups (RCG) from that National Rehabilitation System (NRS), and spinal cord injury fee codes from the Ontario Healthcare Insurance Plan (OHIP). Secondary outcome was the agreement between actual lesion level and RCG/ICD10 coded lesion level. RESULTS: The RCG codes in the NRS have high sensitivity (92%, 95% confidence interval (CI): 87-95%) and specificity (97%, 95% CI: 94-99%) for the identification of true TSCI patients, whereas CIHI-DAD ICD10 codes are highly specific (99%, 95% CI: 95-100) and moderately sensitive (76%, 95% CI: 79-87%). OHIP fee codes had poor sensitivity (64%, 95% CI: 57-71%). Agreement between true lesion level and the NRS and CIHI-DAD coding is good (Kappa of 0.65-0.88 and 0.56 0.70, respectively). CONCLUSION: This study demonstrated that the NRS is able to accurately discriminate between patients with and without a TSCI. A large population of incident and prevalent TSCI patients are identifiable using administrative data. SPONSORSHIP: This study was funded by a grant from the Division of Urology, Western University. PMID- 24216616 TI - Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury. AB - STUDY DESIGN: Two randomized, double-blind, placebo-controlled trials. OBJECTIVE: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI). SETTING: United States and Canada. METHODS: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2 week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors and extensors) and a 7-point Subject Global Impression of treatment (SGI; 1, terrible; 7, delighted). Secondary end points were: Penn Spasm Frequency Scale; the motor/sensory score from the International Standards for Neurological Classification of SCI; Clinician's Global Impression of Change of neurological status; and the International Index of Erectile Function (men) or the Female Sexual Function Index (women). RESULTS: The populations were 212 and 203 patients in the two studies, respectively. Changes from baseline in Ashworth score were -0.15 (placebo) and -0.19 (fampridine-SR) in the first study, and 0.16 (placebo) and -0.28 (fampridine-SR) in the second study. The between treatment difference was not significant for either the Ashworth score or the SGI and, with few exceptions, neither were the secondary end points. Fampridine-SR was generally well tolerated; treatment-emergent adverse events (TEAEs) and serious TEAEs were reported with similar frequency between treatments. CONCLUSION: Fampridine-SR was well tolerated. No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI. PMID- 24216617 TI - Changes in substance P and NK1 receptor immunohistochemistry following human spinal cord injury. AB - STUDY DESIGN: An immunohistological assessment of substance P (SP), its NK1 receptor and claudin-5 in human spinal cord injury (SCI) tissue. OBJECTIVE: To determine whether SP and NK1 receptor immunoreactivity are altered following human traumatic SCI. SETTING: Australia. SUMMARY OF BACKGROUND DATA: SP has been implicated in the development of neurogenic inflammation and subsequent edema development following both traumatic brain injury and ischemic stroke. In these conditions, inhibition of its NK1 receptor has been shown to be neuroprotective as reflected in a reduction of edema and improved functional outcome. However, the role of SP following human SCI has not yet been assessed. METHODS: Archived human SCI tissue was grouped according to survival times: control (no injury; n=5); immediate (death within an hour of the incident; n=6); 2-5 h (n=3); 3 days (n=5); 1 week (n=3); and 3-4 weeks (n=6). Sections were assessed for SP, its NK1 receptor and claudin-5 using immunohistochemical techniques. RESULTS: Following SCI, dorsal horn SP immunoreactivity demonstrated a profound decrease compared with control tissue, indicating the loss of SP with SCI. A marked increase in perivascular NK1 staining was demonstrated after SCI compared with control levels. No obvious change in claudin-5 immunoreactivity was present immediately following injury, however, by 1 week post-SCI, decreased levels were noted. CONCLUSION: This study demonstrates that severe acute traumatic human SCI results in decreased SP and an immediate increase in NK1 receptor immunoreactivity, suggesting that there is a neurogenic inflammatory component following human SCI. PMID- 24216618 TI - A retrospective study on flap complications after pressure ulcer surgery in spinal cord-injured patients. AB - STUDY DESIGN: A retrospective study reporting specific complications of certain skin flaps for treating pressure ulcers. OBJECTIVES: To describe the rate and type of complications after pressure ulcer surgery in patients with spinal cord injury. SETTING: Germany, Rheinland Pfalz. METHODS: We collected data from 352 patients treated with 421 skin flaps to determine the rate and type of complications of each skin flap used. RESULTS: In this study, we analyzed the results of 421 skin flaps in 352 patients with a total of 657 pressure ulcers from January 2006 to December 2010. Our patients had ischial, pelvic, sacral, trochanteric and lower extremity ulcers. Ischial ulcers were most common, followed by sacral and trochanteric ulcers. There were 87 complications in 421 flaps, which was an overall rate of 21%. Suture line dehiscence was the most common complication with 27 cases (31%), followed by 22 cases of infection (25.2%), 17 cases of hematoma (19.5%), 12 cases of partial necrosis (13.7%) and 9 cases of total flap necrosis (10.3%). CONCLUSION: Pressure ulcers in spinal cord injured patients are very common and difficult and expensive to treat. The high rate of complications and the associated costs suggest the importance of evaluating the efficacy of treatment options. Conservative procedures have been standardized, but there still has been limited success in establishing guidelines on how to manage complications arising from flap surgery. Our extensive documentation of flap plastics will be useful managing complications after the surgical treatment of pressure ulcers in spinal cord-injured patients. PMID- 24216619 TI - Alumina-zirconia composites functionalized with laminin-1 and laminin-5 for dentistry: effect of protein adsorption on cellular response. AB - The present paper describes a study on laminin interaction with the surface of two alumina-zirconia composites with different percentages of ZrO2, both with submicrometric grain size. As major molecules within the basement membrane (BM), laminins are important protein fragments for epithelial cell adhesion and migration. On the other hand, alumina-zirconia composites are very attractive materials for dental applications due to their esthetic and mechanical properties. X-Ray photoelectron spectroscopy and atomic force microscopy were used to study the adsorption of two types of laminin, laminin-1 (Ln-1) and laminin-5 (Ln-5), onto the ceramics surfaces. The in vitro cell response was determined by intracellular phosphorylation of major kinases. Ceramics samples functionalized with laminins showed better cellular activation than untreated specimens; furthermore, cellular activation was found to be greater for the composite with higher percentage in zirconia when functionalized with Ln-5, whereas the adsorption of Ln-1 resulted in a greater activation for the alumina rich oxide. PMID- 24216621 TI - Calcium-mediated modulation of Pseudomonas mendocina NR802 biofilm influences the phenanthrene degradation. AB - A potential biofilm forming and phenanthrene utilizing marine bacterium Pseudomonas mendocina NR802 was isolated from Rushukulya, Odisha, East Coast of India. The effect of Ca(2+) and Mg(2+) on biofilm growth and phenanthrene degradation was evaluated. Among the various tested concentrations, 20 mM of Ca(2+) and Mg(2+) showed a significant enhancement in biofilm production by the bacterium. The SEM-EDAX study showed that the elemental composition of the biofilm varied significantly when grown in the presence of Ca(2+) and Mg(2+). The CSLM analysis of biofilms grown in the presence of 20 mM Ca(2+) and Mg(2+) reveal the critical role of these ions on biofilm architectural parameters such as total biomass, biofilm thickness, roughness coefficient and surface to biovolume ratio. Ca(2+) was found to enhance the extracellular polymeric substances (EPS) production and phenanthrene degradation. Ca(2+) enhanced the biofilm growth in a dose dependent manner, whereas Mg(2+) significantly increased the cell growth in biofilm. More than 15% increase in phenanthrene degradation was observed when biofilm was grown in the presence of an additional 20 mM Ca(2+). This study also supports the fundamental role of Ca(2+) in biofilm growth, architecture as well as biofilm-mediated pollutant degradation. PMID- 24216620 TI - Shrinkage of pegylated and non-pegylated liposomes in serum. AB - An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes. PMID- 24216622 TI - Effect of anionic surfactants on grafting density of gelatin modified with PDMS E. AB - The effect of anionic surfactants on the interfacial compatibility in mono epoxy terminated polydimethylsiloxane (PDMS-E) macromonomer and gelatin mixed system was studied by Gibbs free energy (DeltaGM), which played a crucial role in deciding the grafting density of immiscible polymer in heterogeneous system. Aggregation behavior of gelatin chains at boundary between gelatin phase and solvent phase was investigated using viscosity, surface tension and conductivity measurements. Viscosity analysis showed a regular increase in viscosity with the increasing alkyl chain length from C7 to C16 of the homologous alkyl sulfate surfactants. Changes of surface tension exhibited the regular curves of polyelectrolyte-anionic surfactant for alkyl sulfate surfactant systems. The results demonstrated that aggregate structure of gelatin-sulfate surfactants was dominated by electrostatic and hydrophobic interactions, which resulted in a self assembly process of the hydrophobic segments and hydrophilic segments among gelatin chains and surfactant molecules. However, the interactions between gelatin and alkyl sulfonate surfactants were mainly governed by hydrophobic interactions, which induced conformation change of gelatin molecules. Well ordered arrangement of gelatin chains at a fluid interface has observed by high resolution transmission electron microscopy (HR-TEM). It is a key factor to contribute to the reduction of interfacial free energy, which mainly depends on the hydrophobic interaction between gelatin and alkyl sulfate/sulfonate surfactants. MD simulations conclusions are great agreement with our experimental results. PMID- 24216623 TI - Investigating the influence of respiratory motion on the radiation induced bystander effect in modulated radiotherapy. AB - Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy and may contribute towards uncertainties in radiotherapy planning. This study investigates the potential radiobiological implications occurring due to tumour motion in areas of geometric miss in lung cancer radiotherapy. A bespoke phantom and motor-driven platform to replicate respiratory motion and study the consequences on tumour cell survival in vitro was constructed. Human non-small-cell lung cancer cell lines H460 and H1299 were irradiated in modulated radiotherapy configurations in the presence and absence of respiratory motion. Clonogenic survival was calculated for irradiated and shielded regions. Direction of motion, replication of dosimetry by multi-leaf collimator (MLC) manipulation and oscillating lead shielding were investigated to confirm differences in cell survival. Respiratory motion was shown to significantly increase survival for out-of-field regions for H460/H1299 cell lines when compared with static irradiation (p < 0.001). Significantly higher survival was found in the in-field region for the H460 cell line (p < 0.030). Oscillating lead shielding also produced these significant differences. Respiratory motion and oscillatory delivery of radiation dose to human tumour cells has a significant impact on in- and out-of-field survival in the presence of non-uniform irradiation in this in vitro set-up. This may have important radiobiological consequences for modulated radiotherapy in lung cancer. PMID- 24216624 TI - An in vitro and in vivo comparison of the effect of Stevia rebaudiana extracts on different caries-related variables: a randomized controlled trial pilot study. AB - The effect of Stevia extracts on in vitro Streptococcus mutans biofilm formation and in vivo plaque pH was evaluated in this paper. Three 10% solutions containing stevioside, rebaudioside A or sucrose were prepared. MTT assay was used to evaluate microbiological counts in vitro. Twenty volunteers rinsed for 1 min with each solutions, and plaque pH was measured at 7 time points after each rinse. Higher in vitro S. mutans biofilm formation was observed in sucrose solution (p < 0.01). After 5, 10, 15 and 30 min, the sucrose in vivo rinse produced a statistically significantly lower pH value compared to the Stevia extracts (F = 99.45, p < 0.01).Stevia extracts can be considered nonacidogenic. PMID- 24216627 TI - Spatiotemporal representations of rapid visual target detection: a single-trial EEG classification algorithm. AB - Brain computer interface applications, developed for both healthy and clinical populations, critically depend on decoding brain activity in single trials. The goal of the present study was to detect distinctive spatiotemporal brain patterns within a set of event related responses. We introduce a novel classification algorithm, the spatially weighted FLD-PCA (SWFP), which is based on a two-step linear classification of event-related responses, using fisher linear discriminant (FLD) classifier and principal component analysis (PCA) for dimensionality reduction. As a benchmark algorithm, we consider the hierarchical discriminant component Analysis (HDCA), introduced by Parra, et al. 2007. We also consider a modified version of the HDCA, namely the hierarchical discriminant principal component analysis algorithm (HDPCA). We compare single-trial classification accuracies of all the three algorithms, each applied to detect target images within a rapid serial visual presentation (RSVP, 10 Hz) of images from five different object categories, based on single-trial brain responses. We find a systematic superiority of our classification algorithm in the tested paradigm. Additionally, HDPCA significantly increases classification accuracies compared to the HDCA. Finally, we show that presenting several repetitions of the same image exemplars improve accuracy, and thus may be important in cases where high accuracy is crucial. PMID- 24216628 TI - Numerical safety study of currents induced in the patient during rotations in the static field produced by a hybrid MRI-LINAC system. AB - MRI-LINAC is a new image-guided radiotherapy treatment system that combines magnetic resonance imaging (MRI) and a linear particle accelerator (LINAC) into a single unit. Moving (i.e., rotating or translating) the patient inside the strong magnetic field of the split MRI-LINAC magnet can potentially induce high levels of electric fields and corresponding current densities in the conducting tissues. The prediction and assessment of patient safety in terms of electromagnetic field exposure have received very little attention for a split cylindrical MRI magnet configuration, especially in the vicinity of the gap region. In this novel numerical study, based on the quasi-static finite-difference method, rotation induced electric fields and current densities are calculated considering a split 1-T magnet and a tissue-accurate 2-mm-resolution human body model. The patient was modeled in both axial and radial orientations relative to the magnet gap in a number of treatment/imaging scenarios. It was found that rotating the patient in the radial orientation produced an order of magnitude larger field exposure in the central nervous system than when the patient was rotated in the axial orientation. Also, rotating the patient with periods lower than about Trot = 43.3 s may result in field exposures above the limits set out in the international safety guidelines. The novel results of this investigation can provide useful insights into the safe use of the MRI-LINAC technology and optimal orientations of the patient during the treatment. PMID- 24216625 TI - Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice. AB - Saussurea lappa is a traditional herbal medicine used for to treat various inflammatory diseases. In this study, we investigated the protective effects of S. lappa against atopic dermatitis using human keratinocyte HaCaT cells, murine mast cell line MC/9 cells, and a house dust mite-induced atopic dermatitis model of Nc/Nga mice. Treatment with the S. lappa caused a significant reduction in the mRNA levels and production of inflammatory chemokines and cytokine, including thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) in tumor necrosis factor-alpha/interferone-gamma stimulated HaCaT cells. S. lappa exhibited the significant reduction in histamine production in MC/9 cells. In the atopic dermatitis model, S. lappa significantly reduced the dermatitis score and serum IgE and TARC levels. In addition, the back skin and ears of S. lappa-treated Nc/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. In conclusion, an extract of S. lappa effectively suppressed the development of atopic dermatitis, which was closely related to the reduction of chemokines and cytokine. Our study suggests that S. lappa may be a potential treatment for atopic dermatitis. PMID- 24216629 TI - Galvanic coupling transmission in intrabody communication: a finite element approach. AB - Galvanic coupling in intrabody communication (IBC) is a technique that couples low-power and low-frequency voltages and currents into the human body, which acts as a transmission medium, and thus constitutes a promising approach in the design of personal health devices. Despite important advances being made during recent years, the investigation of relevant galvanic IBC parameters, including the influence of human tissues and different electrode configurations, still requires further research efforts. The objective of this work is to disclose knowledge into IBC galvanic coupling transmission mechanisms by using a realistic 3-D finite element model of the human arm. Unlike other computational models for IBC, we have modeled the differential configuration of the galvanic coupling as a four port network in order to analyze the electric field distribution and current density through different tissues. This has allowed us to provide an insight into signal transmission paths through the human body, showing them to be considerably dependent on variables such as frequency and inter-electrode distance. In addition, other important variables, for example bioimpedance and pathloss, have also been analyzed. Finally, experimental measurements were also carried out for the sake of validation, demonstrating the reliability of the model to emulate in general forms some of the behaviors observed in practice. PMID- 24216630 TI - Iterative method to detect atrial activations and measure cycle length from electrograms during atrial fibrillation. AB - Atrial fibrillation (AF) electrograms are characterized by varying morphologies, amplitudes, and cycle lengths (CLs), presenting a challenge for automated detection of individual activations and the activation rate. In this study, we evaluate an algorithm to detect activations and measure CLs from AF electrograms. This algorithm iteratively adjusts the detection threshold level until the mean CL converges with the median CL to detect all individual activations. A total of 291 AF electrogram recordings from 13 patients (11 male, 58 +/- 10 years old) undergoing AF ablation were obtained. Using manual markings by two independent reviewers as the standard, we compared the cycle length iteration algorithm with a fixed threshold algorithm and dominant frequency (DF) for the estimation of CL. At segment lengths of 10 s, when comparing the algorithm detected to the manually detected activation, the undersensing, oversensing, and total discrepancy rates were 2.4%, 4.6%, and 7.0%, respectively, and with absolute differences in mean and median CLs were 7.9 +/- 9.6 ms and 5.6 +/- 6.8 ms, respectively. These results outperformed DF and fixed threshold-based measurements. This robust method can be used for CL measurements in either real-time and offline settings and may be useful in the mapping of AF. PMID- 24216631 TI - An integrated system for wireless capsule endoscopy in a liquid-distended stomach. AB - The design and development of a functional integrated system for gastroscopy is reported in this paper. The device takes advantage of four propellers enabling locomotion in a liquid environment and generating a maximum propulsive force of 25.5 mN. The capsule has been equipped with a miniaturized wireless vision system that acquires images with a frame rate of 30 fps (frames per second). The overall size of the capsule is 32 mm in length and 22 mm in diameter, with the possibility of decreasing the diameter to swallowable dimensions. The capsule is remotely controlled by the user who can intuitively drive the device by looking at the video streaming on the graphical interface. The average speed of the device is 1.5 cm/s that allows for a fine control of the capsule motion as demonstrated in experimental tasks consisting of passing through circular targets. The video system performances have been characterized by evaluating the contrast, the focus, and the capability of acquiring and perceiving different colors. The usability of the device has been tested on bench and on explanted tissues by three users in real time target-identification tasks, in order to assess the success of the integration process. The lifetime of the capsule with active motors and vision system is 13 min, that is, a timeframe consistent with traditional gastroscopic examinations. PMID- 24216632 TI - Perturbation amplitude affects linearly estimated neuromechanical wrist joint properties. AB - System identification techniques have been used to separate intrinsic muscular and reflexive contributions to joint impedance, which is an essential step in the proper choice of patient specific treatment. These techniques are, however, only well developed for linear systems. Assuming linearity prescribes the neuromuscular system to be perturbed only around predefined operating points. In this study, we test the validity of a commonly used linear model by analyzing the effects of flexion-extension displacement amplitude (2( degrees ), 4( degrees ), and 8( degrees )) on damping, stiffness, and reflex gain of the wrist joint, at different background torque levels (0, 1, and 2 N . m). With displacement amplitude, intrinsic damping increased, while intrinsic stiffness and reflex gains decreased. These changes were dependent on the level of wrist torque. The dependency of the neuromuscular system properties on even small variations in angular displacement is evident and has to be accounted for when comparing different studies and clinical interpretations using linear identification techniques. Knowledge of the behavior of the neuromuscular system around operating points is an essential step toward the development of nonlinear models that allow for discrimination between patients and controls in a larger range of loading conditions. PMID- 24216633 TI - Assessment of laparoscopic skills based on force and motion parameters. AB - Box trainers equipped with sensors may help in acquiring objective information about a trainee's performance while performing training tasks with real instruments. The main aim of this study is to investigate the added value of force parameters with respect to commonly used motion and time parameters such as path length, motion volume, and task time. Two new dynamic bimanual positioning tasks were developed that not only requiring adequate motion control but also appropriate force control successful completion. Force and motion data for these tasks were studied for three groups of participants with different experience levels in laparoscopy (i.e., 11 novices, 19 intermediates, and 12 experts). In total, 10 of the 13 parameters showed a significant difference between groups. When the data from the significant motion, time, and force parameters are used for classification, it is possible to identify the skills level of the participants with 100% accuracy. Furthermore, the force parameters of many individuals in the intermediate group exceeded the maximum values in the novice and expert group. The relatively high forces used by the intermediates argue for the inclusion of training and assessment of force application during tissue handling in future laparoscopic skills training programs. PMID- 24216634 TI - Obesity stigma: a persistent problem, a possible solution. PMID- 24216635 TI - Reply: To PMID 23711562. PMID- 24216636 TI - Effect of parity on first-trimester uterine artery Doppler indices and their predictive value for pregnancy complications. AB - AIM: To investigate the relationship between parity and first-trimester uterine artery Doppler indices and determine their predictive value for pregnancy complications. METHODS: In 679 singleton pregnancies (388 parous and 291 nulliparous) attending for routine care at 11-14 weeks of gestation, we recorded maternal characteristics, medical and obstetric history, the presence of protodiastolic notching and measured uterine artery resistance index (RI). RESULTS: Parous women had a lower prevalence of bilateral notches (64 vs. 77.6%; p = 0.0002), median level of RI did not show any significant difference. In parous cases complicated with pregnancy-induced hypertension (PIH) (0.78 vs. 0.70; p = 0.0003) or miscarriage (0.86 vs. 0.71; p = 0.0003) mean levels of RI were significantly higher than in the nulliparous cases. By using mean RI we could predict the cases with PIH (area under curve (AUC) 0.63; p = 0.012), early PIH (AUC 0.84; p < 0.0001) and miscarriage (AUC 0.87; p < 0.0001) in the group of parous women. CONCLUSION: Parity has a significant effect on uterine artery Doppler findings in the first trimester of pregnancy. In the group of parous women the mean level of RI had a higher predictive value for miscarriage, early PIH and PIH. PMID- 24216638 TI - Multiring large-mode-area delivery fiber for high power. AB - The study presents a novel design of multiring delivery fiber with large mode area for high power. Using a FiberCAD method, we investigated a fiber whose core is surrounded by alternative low- and high-index rings. Based on our calculation, the effective area is 400 MUm2 at 1.08 MUm, larger than the ~280 MUm2 of conventional step-index fiber (20/400). The macrobending loss at 1.08 MUm is estimated to be 1*10(-3) dB/m, approximately one-third that of conventional step index fiber (20/400). The single-mode operation can be achieved by the macrobending loss contrast between the fundamental mode (<1 dB/m) and high-order mode (>100 dB/m). The results indicate that multiring delivery fiber fabricated by modified chemical vapor deposition process is a promising candidate for high power transmission. PMID- 24216639 TI - Electro-optical characteristics of holographic polymer dispersed liquid crystal gratings doped with nanosilver. AB - We report on the synthesis and characteristics of a holographic polymer dispersed liquid crystal (H-PDLC) switchable grating based on nano-Ag particles. The influence of doping different concentrations of nano-Ag on the diffraction efficiency, driving voltage, and response time of the H-PDLC grating is investigated. The best grating characteristics were achieved with 0.05% nano-Ag doping. Calculated and experimental results reveal that the improvement of the characteristics is likely due to the surface plasmon effect of nano-Ag. PMID- 24216640 TI - Huygens-Feynman-Fresnel principle as the basis of applied optics. AB - The main relationships of wave optics are derived from a combination of the Huygens-Fresnel principle and the Feynman integral over all paths. The stationary phase approximation of the wave relations gives the correspondent relations from the point of view of geometrical optics. PMID- 24216641 TI - Phase retrieval and Zernike decomposition using measured intensity data and the estimated electric field. AB - A new direct search phase retrieval technique for determining the optical prescription of an imaging system in terms of Zernike coefficients is described. The technique provides coefficient estimates without the need to defocus point source images to generate phase diversity by using electric field (E-field) estimates in addition to intensity data. Numerical analysis shows that E-field patterns in the image plane produced by the Zernike polynomials are less correlated with each other than the intensity patterns. Therefore, the E-field pattern provides more information for Zernike coefficient estimation than the intensity pattern alone. The phase retrieval is accomplished through an iterative process that uses the measured point source data to estimate the E-field pattern in the image plane with the Gerchberg-Saxton (GS) algorithm. The estimated E field is correlated with a modeled E-field to produce estimates of the Zernike coefficients. Then the coefficients that minimize the error between measured data and the intensity model are selected. By using E-field estimates rather than phase estimates from the GS algorithm, the limitations of phase unwrapping for Zernike decomposition are avoided. Simulated point source data shows the new phase retrieval algorithm avoids getting trapped in local minima over a wide range of random aberrations. Experimental point source data are used to demonstrate the phase retrieval effectiveness. PMID- 24216642 TI - Gain optimization of fiber optical parametric amplifier based on genetic algorithm with pump depletion. AB - A method to optimize the gain of a fiber optical parametric amplifier (FOPA) is presented by using a genetic algorithm (GA), which can determine the parameters of FOPA and avoid the trouble of trial and error to achieve it. The effect of pump depletion on the gain characteristic of the FOPA is emphasized, and the effects of the fiber length, the wavelength, and the power of two pumps on bandwidth, flatness, and magnitude of the gain spectrum are also studied. According to the presentation, fiber length and the wavelength of the two pumps are selected to be the variable parameters in the GA. When the parameters of the fiber are determined, with the numerical simulation, the optimum combination scheme between those chosen variables could be obtained by the algorithms with the result of the gain optimization of FOPA. PMID- 24216643 TI - Probability density functions of power-in-bucket and power-in-fiber for an infrared laser beam propagating in the maritime environment. AB - Irradiance fluctuations of an infrared laser beam from a shore-to-ship data link ranging from 5.1 to 17.8 km are compared to lognormal (LN), gamma-gamma (GG) with aperture averaging, and gamma-Laguerre (GL) distributions. From our data analysis, the LN and GG probability density function (PDF) models were generally in good agreement in near-weak to moderate fluctuations. This was also true in moderate to strong fluctuations when the spatial coherence radius was smaller than the detector aperture size, with the exception of the 2.54 cm power-in bucket (PIB) where the LN PDF model fit best. For moderate to strong fluctuations, the GG PDF model tended to outperform the LN PDF model when the spatial coherence radius was greater than the detector aperture size. Additionally, the GL PDF model had the best or next to best overall fit in all cases with the exception of the 2.54 cm PIB where the scintillation index was highest. The GL PDF model also appears to be robust for off-of-beam center laser beam applications. PMID- 24216644 TI - Multigas detection using a sample-grating distributed Bragg reflector diode laser. AB - A sample-grating distributed Bragg reflector (SG-DBR) laser with 18 preprogrammed channels operating at 1540-1580 nm is characterized and compared for use as a source of tunable diode laser gas absorption spectroscopy. Two gases, CO and CO2, were targeted in this study by direct absorption spectroscopy and wavelength modulation spectroscopy with second-harmonic detection. In addition, the detectability of sample optical thickness is reported. Potential extensions of this research in the future are assessed using the SG-DBR diode laser as a source for tunable diode laser gas absorption spectroscopy. PMID- 24216645 TI - Electrically controlled diffraction employing electrophoresis, supercapacitance, and total internal reflection. AB - The reflectance of a surface can be altered by controlling the concentration of dye ions in a region adjacent to an optically transparent and electrically conductive thin film. We present a method for nonmechanical light deflection achieved by altering the reflectance of a diffraction grating, an approach that creates new diffraction peaks that lie between those associated with the original grating spacing. We have demonstrated this effect by applying an electrical potential difference between interdigitated indium-tin oxide (ITO) electrodes and measuring the intensity of one of the new diffraction peaks. The measured diffraction peak intensities were found to reversibly deflect approximately 7% of the reflected light to previously nonexistent peaks. The diffraction grating was formed by patterning a thin film of planar, untreated ITO on a glass substrate using standard photolithography techniques. The size scale for this method of electrically controlled diffraction is limited only by the lithographic process; thus there is potential for the grating to deflect light to angles greater than those achievable using other methods. This approach could be used in applications such as telecommunications, where large deflection angles are required, or other applications where alternate beam-steering methods are cost prohibitive. PMID- 24216646 TI - Transparency and stability of Ag-based metal-dielectric multilayers. AB - We fabricated and tested periodic metal (Ag)-dielectric (SiO2 or TiO2) multilayers with transparency bands in the visible range. For samples with Ag TiO2 interfaces, the optical properties exhibited relatively poor predictability, likely due to oxidation of the Ag layers. Ag/SiO2-based multilayers were found to be more predictable and stable, but the relatively low refractive index of SiO2 limits their inherent transparency and pass-band bandwidth. We show that termination of the multilayer with a single high-index layer reduces the admittance mismatch with the ambient media, and thus improves the properties of the transparency band. PMID- 24216647 TI - Multiple-image encryption and authentication with sparse representation by space multiplexing. AB - A multiple-image encryption and authentication approach by space multiplexing has been proposed. The redundant spaces in the previous security systems employing sparse representation strategy are optimized. With the proposal the information of multiple images can be integrated into a synthesized ciphertext that is convenient for storage and transmission. Only when all the keys are correct can the information of the primary images be authenticated. Computer simulation results have demonstrated that the proposed method is feasible and effective. Moreover, the proposal is also proved to be robust against occlusion and noise attacks. PMID- 24216648 TI - High-power diode-side-pumped rod Tm:YAG laser at 2.07 MUm. AB - We report a high-power diode-laser (LD) side-pumped rod Tm:YAG laser of around 2 MUm. The laser was water-cooled at 8 degrees C and yielded a maximum output power of 267 W at 2.07 MUm, which is the highest output power for an all solid-state cw 2.07 MUm rod Tm:YAG laser reported as far as we know. The corresponding optical optical conversion efficiency was 20.7%, and the slope efficiency was about 29.8%, respectively. PMID- 24216649 TI - Ultrashort hybrid metal-insulator plasmonic directional coupler. AB - An ultrashort plasmonic directional coupler based on the hybrid metal-insulator slab waveguide is proposed and analyzed at the telecommunication wavelength of 1550 nm. It is first analyzed using the supermode theory based on mode analysis via the transfer matrix method in the interaction region. Then the 2D model of the coupler, including transition arms, is analyzed using a commercial finite element method simulator. The hybrid slab waveguide is composed of a metallic layer of silver and two dielectric layers of silica (SiO2) and silicon (Si). The coupler is optimized to have a minimum coupling length and to transfer maximum power considering the layer thicknesses as optimization variables. The resulting coupling length in the submicrometer region along with a noticeable power transfer efficiency are advantages of the proposed coupler compared to previously reported plasmonic couplers. PMID- 24216650 TI - Study on active lap tool influence function in grinding 1.8 m primary mirror. AB - We present a theoretical modeling method to predict the ring tool influence function (TIF) based on the computer-controlled active lap process. The gap on the lap-grinding layer is considered, and its influence on the ring TIF is analyzed too. The relationship between the shape of the ring TIF and the lap workpiece rotation speed ratio is discussed in this paper. The recipe for calculating dwell time for axisymmetric fabrication is discussed. The grinding process of a 1.8 m primary mirror is improved based on these results. The grinding process is accomplished after 30 circles of grinding, and the surface shape error is from PV 82 MUm RMS 16.4 MUm reduced to PV 13.5 MUm RMS 2.5 MUm. PMID- 24216651 TI - Photonic generation of ultrawideband signals based on a gain-switched semiconductor laser with optical feedback. AB - A simple photonic approach to generate ultrawideband (UWB) pulse signals utilizing a gain-switched semiconductor laser with optical feedback is proposed and demonstrated. The RF spectrum of the generated chaotic UWB signals has a -10 dB bandwidth of 9 GHz and central frequency of 6.6 GHz (fractional bandwidth of 155%), which is consistent with the Federal Communications Commission indoor mask. The central frequency and -10 dB bandwidth can be tuned by adjusting the bias current and feedback strength of the semiconductor laser. After transmission through a 30 km single-mode fiber, the spectrum shape of the chaotic UWB signals is almost unaffected by the chromatic dispersion of the fiber. PMID- 24216652 TI - Tunable band notch filters by manipulating couplings of split ring resonators. AB - The couplings between single/dual split ring resonators (SRRs) and their mirror images in a rectangular waveguide are systematically investigated through theoretical analysis and experimental measurements. Such couplings can be manipulated mechanically by rotating the SRRs along a dielectric rod and/or shifting the SRRs up/down along the sidewall of the rectangular waveguide, resulting in shifts of the resonant frequencies and modulations of the resonant magnitudes. These controllable properties of SRRs pave the routers toward designing tunable band notch filters. In particular, it is experimentally demonstrated that the designed filters possess 7.5% tuning range in the X-band. PMID- 24216654 TI - Electric-induced oxide breakdown of a charge-coupled device under femtosecond laser irradiation. AB - A femtosecond laser provides an ideal source to investigate the laser-induced damage of a charge-coupled device (CCD) owing to its thermal-free and localized damage properties. For conventional damage mechanisms in the nanosecond laser regime, a leakage current and degradation of a point spread function or modulation transfer function of the CCD are caused by the thermal damages to the oxide and adjacent electrodes. However, the damage mechanisms are quite different for a femtosecond laser. In this paper, an area CCD was subjected to Ti: sapphire laser irradiation at 800 nm by 100 fs single pulses. Electric-induced oxide breakdown is considered to be the primary mechanism to cause a leakage current, and the injured oxide is between the gate and source in the metal-oxide semiconductor field-effect transistor (MOSFET) structure for one CCD pixel. Optical microscopy and scanning electron microscopy are used to investigate the damaged areas and the results show that the electrodes and the oxide underneath are not directly affected by the femtosecond laser, which helps to get rid of the conventional damage mechanisms. For the primary damage mechanism, direct damage by hot carriers, anode hole injection, and an enlarged electric field in the insulating layer are three possible ways to cause oxide breakdown. The leakage current is proved by the decrease of the resistance of electrodes to the substrate. The output saturated images and the dynamics of an area CCD indicate that the leakage current is from an electrode to a light sensing area (or gate to source for a MOSFET), which proves the oxide breakdown mechanism. PMID- 24216655 TI - Real-time visual sensing system achieving high-speed 3D particle tracking with nanometer resolution. AB - This paper presents a real-time visual sensing system, which is created to achieve high-speed three-dimensional (3D) motion tracking of microscopic spherical particles in aqueous solutions with nanometer resolution. The system comprises a complementary metal-oxide-semiconductor (CMOS) camera, a field programmable gate array (FPGA), and real-time image processing programs. The CMOS camera has high photosensitivity and superior SNR. It acquires images of 128*120 pixels at a frame rate of up to 10,000 frames per second (fps) under the white light illumination from a standard 100 W halogen lamp. The real-time image stream is downloaded from the camera directly to the FPGA, wherein a 3D particle tracking algorithm is implemented to calculate the 3D positions of the target particle in real time. Two important objectives, i.e., real-time estimation of the 3D position matches the maximum frame rate of the camera and the timing of the output data stream of the system is precisely controlled, are achieved. Two sets of experiments were conducted to demonstrate the performance of the system. First, the visual sensing system was used to track the motion of a 2 MUm polystyrene bead, whose motion was controlled by a three-axis piezo motion stage. The ability to track long-range motion with nanometer resolution in all three axes is demonstrated. Second, it was used to measure the Brownian motion of the 2 MUm polystyrene bead, which was stabilized in aqueous solution by a laser trapping system. PMID- 24216656 TI - Study on effective cleaning of gold layer from fused silica mirrors using nanosecond-pulsed Nd:YAG laser. AB - A study on effective laser cleaning of gold layer deposited on fused silica substrates used in beamlines of synchrotron radiation (SR) sources using nanosecond-pulsed Nd:YAG laser has been carried out. The influence of pulse duration, beam incidence angle, spot overlapping, laser fluence, and number of passes on cleaning efficiency has been investigated. An approximately 48 nm thick gold layer from a mirror surface area of ~48 cm2 has been cleaned in 3 min. Laser clean quality and efficiency has been analyzed using microscope, scanning electron microscope (SEM), and angle-dependent reflectivity measurement techniques using SR beamline. Optimization of cleaning parameters resulted in a cleaning efficiency of ~98%. This study provides an alternate and low-cost solution for reuse of gold-coated, damaged mirrors. PMID- 24216657 TI - Optical-assembly periodic structure of ferrofluids in a liquid core/metal cladding optical waveguide. AB - We present a novel and simple mechanism for the fabrication of periodic microstructure based on a ferrofluids core/metal cladding optical waveguide chip. The ultrahigh-order modes excited in the millimeter scale guiding layer lead to the ordered particle aggregates in ferrofluids without applying a magnetic field. Since the absorption of photons by the extremely dilute ferrofluids is extremely small and the Soret effect is not noticeable, a tentative explanation in terms of the optical trapping effect is proposed. Furthermore, this scheme exhibits all optically tunable reflectivity and lateral Goos-Hanchen shift, which potentially may be for practical use in novel optical devices. PMID- 24216658 TI - Calibrating a high-resolution wavefront corrector with a static focal-plane camera. AB - We present a method to calibrate a high-resolution wavefront (WF)-correcting device with a single, static camera, located in the focal-plane; no moving of any component is needed. The method is based on a localized diversity and differential optical transfer functions to compute both the phase and amplitude in the pupil plane located upstream of the last imaging optics. An experiment with a spatial light modulator shows that the calibration is sufficient to robustly operate a focal-plane WF sensing algorithm controlling a WF corrector with 40,000 degrees of freedom. We estimate that the locations of identical WF corrector elements are determined with a spatial resolution of 0.3% compared to the pupil diameter. PMID- 24216659 TI - Retrieving controlled motion parameters using two speckle pattern analysis techniques: spatiotemporal correlation and the temporal history speckle pattern. AB - This paper presents simulation of speckle activity through controlling a moving plate. We present two procedures to extract the initial movement frequency and amplitude, either through correlation calculus or through processing the temporal history of the speckle pattern. We compare and discuss these two methods in terms of efficiency and the ability to retrieve motion parameters. The correlation technique seems to be more suitable for monitoring biospeckle activity as it provides more reliable parameter estimation than the temporal history of the speckle pattern. The evolution of temporal history of the speckle pattern parameters and their response sensibility with amplitude and frequency variations have been studied and quantified. Briers contrast appears to depend only on movement amplitude, whereas inertia moment varies with amplitude and frequency. PMID- 24216660 TI - Study of the nonuniform behavior of temperature sensitivity in bare and embedded fiber Bragg gratings: experimental results and analysis. AB - This paper presents an experiment and analysis on the factors affecting nonlinear evolution of Bragg wavelength with change in temperature in typical bare and embedded fiber Bragg grating-based (FBG) temperature sensors. The purpose of the study was to find the constants in the function required to evaluate temperature from Bragg wavelength shift. The temperature sensitivity of bare FBGs was found to increase with temperature elevation, and is different for FBGs written in different fiber types. The average temperature sensitivity increased by about 20% when the bare FBG temperature was elevated from 25 degrees C to 525 degrees C. The average temperature sensitivity of the embedded FBG sensor, investigated in the temperature range of 30 degrees C-90 degrees C, was a factor of 2-3 times larger than for bare FBG, depending on its fastened length with the substrate. Analytically, it is shown that the nonuniform behavior of temperature sensitivity in bare FBGs is the result of both the thermal expansion effect of the fiber and the temperature derivatives of the effective refractive index. The strain transfer and temperature coefficients of thermal expansion of the substrate affect the nonuniform behavior of temperature sensitivity in embedded FBG sensors. PMID- 24216661 TI - Optical electric-field sensor based on angular optical bias using single beta BaB2O4 crystal. AB - A novel optical electric-field sensor is proposed and demonstrated in experiment by use of a single beta barium borate (beta-BaB2O4, BBO) crystal. The optical sensing unit is only composed of one BBO crystal and two polarizers. An optical phase bias of 0.5pi is provided by using natural birefringence in the BBO crystal itself. A small angle (e.g., 0.6 degrees ) between the sensing light beam and principal axis of the crystal is required in order to produce the above optical bias. Thus the BBO crystal is used as the electric-field-sensing element and quarter waveplate. The ac electric field in the range of (1.4-703.2) kV/m has been measured with measurement sensitivity of 1.39 mV/(kV/m) and nonlinear error of 0.6%. Compared with lithium niobate crystal used as an electric-field sensor, main advantages of the BBO crystal include higher measurement sensitivity, compact configuration, and no ferroelectric ringing effect. PMID- 24216662 TI - Mimicking bicolor by changing the reflectance of the substrate in a one dimensional periodic structure. AB - In nature, some beetles can display bicolor on their elytra. In order to explore the bicolor mechanism, we experimentally studied the optical and structural properties of the Carabus lafossei beetle. We found a multilayer structure in the cuticle of the beetle. Due to the different multilayer thicknesses in different areas, the beetle displayed bicolor. Here, we provide another approach to fabricate bicolor by depositing the same multilayer stack on a substrate with different reflectances at different areas. In this paper, the substrate with different reflectances is achieved by prefabricating sculpted hexagons (SU-8) on a silicon substrate. By coating a (ZnS/MgF2)3.5 multilayer, the sculpted structure displays green color at the ridges (SU-8/silicon area) and yellow color at the basins (silicon area). PMID- 24216663 TI - Stoichiometry of laser ablated brass nanoparticles in water and air. AB - We report on the stoichiometric analysis of laser ablated brass plasma nanoparticles (NPs) in water and ambient air. Morphological study of the deposited NPs in water showed smaller spherical NPs compared to micrometer sized spherical particles in air. The smaller particles were Zn enriched and the concentration decreased with increases in size. Photoluminescence of particles at 380 nm corresponding to ZnO showed higher concentrations of Zn with smaller sized deposited NPs, whereas the micrometer sized particles showed multiple peaks at 415 and 440 nm, which implied that there was an abundance of the Cu fraction in the NPs. Plasma plume parameters, electron temperature, electron density, and evolution of the plasma plume were studied using optical emission spectroscopy and 2-dimensional imaging of the plume. The mass ablation rate in water was observed to be greater than that in air. Higher electron density and temperature of the plasmoid in water was attributed to confinement of the plasma plume near the target surface in water. PMID- 24216664 TI - Analysis of diffraction wavefront in visible-light point-diffraction interferometer. AB - As a key element in point-diffraction interferometer (PDI), the diffraction pinhole determines the sphericity of the reference wavefront and achievable precision of the testing system. The point-diffraction wavefront error, aperture angle, and light transmittance in the PDI operating at visible light, which are determined by pinhole dimension, are analyzed based on finite difference time domain (FDTD) method. The study shows that an aperture angle about 75 degrees can be obtained with a 1 MUm pinhole diameter, and the corresponding testing precision is better than root mean square lambda/1000 within 0.35 NA. Both the numerical simulation and experiments have been carried out to demonstrate the feasibility of the proposed analysis approach, and a good agreement is obtained between calculated and measured parameters in visible-light PDI. The proposed simulation approach with the FDTD method provides a feasible way to analyze the diffraction wavefront in visible-light PDI, as well as a powerful tool for the design and optimization of PDI system. PMID- 24216665 TI - Fast analyses and designs of long-period fiber grating devices with cosine-class apodizations by using Fourier mode coupling theory. AB - This paper presents an analytical approach to fast analyzing and designing long period fiber grating (LPFG) devices with cosine-class apodizations by using the Fourier mode coupling (FMC) theory. The LPFG devices include LPFGs, LPFG-based in fiber Mach-Zehnder and Michelson interferometers, which are apodized with the cosine-class windows of cosine, raised-cosine, Hamming, and Blackman. The analytic models (AMs) of the apodized LPFG devices are derived from the FMC theory, which are compared with the preferred transfer matrix (TM) method to confirm their efficiencies and accuracies. The AM-based analyses are achieved and verified to be accurate and efficient enough. The AM-based analysis efficiency is improved over 1318 times versus the TM-based one. Based on the analytic models, an analytic design algorithm is proposed and then applied to designing these LPFG devices, which has the complexity of O(N) and is far faster than the existing design methods. PMID- 24216666 TI - Field-based dynamic light scattering microscopy: theory and numerical analysis. AB - We present a theoretical framework for field-based dynamic light scattering microscopy based on a spectral-domain optical coherence phase microscopy (SD OCPM) platform. SD-OCPM is an interferometric microscope capable of quantitative measurement of amplitude and phase of scattered light with high phase stability. Field-based dynamic light scattering (F-DLS) analysis allows for direct evaluation of complex-valued field autocorrelation function and measurement of localized diffusive and directional dynamic properties of biological and material samples with high spatial resolution. In order to gain insight into the information provided by F-DLS microscopy, theoretical and numerical analyses are performed to evaluate the effect of numerical aperture of the imaging optics. We demonstrate that sharp focusing of fields affects the measured diffusive and transport velocity, which leads to smaller values for the dynamic properties in the sample. An approach for accurately determining the dynamic properties of the samples is discussed. PMID- 24216667 TI - Modified detection scheme for locating phase jumps and reducing detection errors. AB - Most phase unwrapping algorithms shift the 2pi phase jump pixels to obtain the unwrapped phases, while most filtering algorithms remove the noisy pixels to avoid the fault of unwrapped phases. Thus, finding the positions of phase jump pixels and noisy pixels is important. This study proposed a modified detection scheme developed from the originally published noise and phase jump detection scheme [Opt. Express 19, 3086 (2011)]. The original detection scheme finds the noise positions and phase jump positions, and then marks these pixels in two maps, namely, the noise map and the phase jump map. One 2pi phase jump contains a 2pi-high position and a 0-low position. However, the original detection scheme usually finds a 2pi-high position and misses a corresponding 0-low position, or usually finds a 0-low position and misses a corresponding 2pi-high position. Moreover, the original detection scheme produces detection errors, containing the repeated pixels of phase jump or the wrong pixels generated by noise. Fortunately, the proposed modified detection scheme can find both the 2pi-high position and the corresponding 0-low position. Moreover, the detection errors are also reduced by the proposed modified detection scheme. The robustness of the modified detection scheme is demonstrated both numerically and experimentally. PMID- 24216668 TI - Process variation in silicon photonic devices. AB - An array of passive silicon-on-insulator optical devices is laid out in repeating patterns on four foundry-fabricated wafers. The physical and optical characterization of these microrings, racetrack resonators, and directional couplers are found to exhibit significant variation in optical response. A device heating experiment carried out on a number of different devices demonstrates that thermal effects are independent of the device's location on the wafer. An analysis of the variation of the optical responses of the room-temperature devices is used to determine the process variation. We find that if we form successive arrays of the values of a quantity of interest (the peak wavelength of a transfer function) at a single device at some point on the wafer, and then increase the size of the array by including the values of the devices at ever greater distances from the original, then the variance of the values of the successive arrays increases linearly with the linear extent of the sample. That is, the process variation exhibits "random walk" pattern with spatial extent. We express the process variation in units of variance per length and find that our measured values agree with others in the literature; that is, the process variation is approximately 1 nm2/cm. PMID- 24216669 TI - Fringe-projection profilometry based on two-dimensional empirical mode decomposition. AB - In 3D shape measurement, because deformed fringes often contain low-frequency information degraded with random noise and background intensity information, a new fringe-projection profilometry is proposed based on 2D empirical mode decomposition (2D-EMD). The fringe pattern is first decomposed into numbers of intrinsic mode functions by 2D-EMD. Because the method has partial noise reduction, the background components can be removed to obtain the fundamental components needed to perform Hilbert transformation to retrieve the phase information. The 2D-EMD can effectively extract the modulation phase of a single direction fringe and an inclined fringe pattern because it is a full 2D analysis method and considers the relationship between adjacent lines of a fringe patterns. In addition, as the method does not add noise repeatedly, as does ensemble EMD, the data processing time is shortened. Computer simulations and experiments prove the feasibility of this method. PMID- 24216670 TI - Phase- and tilt-shift determinations by analysis of spectra sidebands for phase shift interferometers. AB - A spatial frequency domain method is presented to deal with tilt-shift errors and random phase shift in temporal phase-shift interferometry. The proposed method determines tilt shift and phase shift by analyzing positions and phase variances of sidebands in spatial frequency domain. The method is computationally fast for it is noniterative and needs only one 2D Fourier transform for each spatial carrier interferogram. No initial estimations are required and no ambiguous results are generated with the proposed method. Simulations indicate that the proposed method could detect tilt shift and piston phase shift with high accuracy. Results of experiments conducted in the presence of vibration demonstrate that the proposed method could alleviate fluctuations in the retrieved phase map. The method could be applied to interferometers that are uncalibrated or with an unbalanced piezoelectric transducer, besides interferometers in unsteady conditions. PMID- 24216671 TI - GOES-R Advanced Baseline Imager: spectral response functions and radiometric biases with the NPP Visible Infrared Imaging Radiometer Suite evaluated for desert calibration sites. AB - The Advanced Baseline Imager (ABI), which will be launched in late 2015 on the National Oceanic and Atmospheric Administration's Geostationary Operational Environmental Satellite R-series satellite, will be evaluated in terms of its data quality postlaunch through comparisons with other satellite sensors such as the recently launched Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership satellite. The ABI has completed much of its prelaunch characterization and its developers have generated and released its channel spectral response functions (response versus wavelength). Using these responses and constraining a radiative transfer model with ground reflectance, aerosol, and water vapor measurements, we simulate observed top of atmosphere (TOA) reflectances for analogous visible and near infrared channels of the VIIRS and ABI sensors at the Sonoran Desert and White Sands National Monument sites and calculate the radiometric biases and their uncertainties. We also calculate sensor TOA reflectances using aircraft hyperspectral data from the Airborne Visible/Infrared Imaging Spectrometer to validate the uncertainties in several of the ABI and VIIRS channels and discuss the potential for validating the others. Once on-orbit, calibration scientists can use these biases to ensure ABI data quality and consistency to support the numerical weather prediction community and other data users. They can also use the results for ABI or VIIRS anomaly detection and resolution. PMID- 24216672 TI - An editor's role and responsibility. AB - Following an editorial emphasizing the importance of reviewers, Applied Optics' Editor in Chief Joseph N. Mait explains the critical role of the editor. PMID- 24216673 TI - Easy-to-use augmented reality neuronavigation using a wireless tablet PC. AB - BACKGROUND/AIMS: Augmented reality (AR) technology solves the problem of view switching in traditional image-guided neurosurgery systems by integrating computer-generated objects into the actual scene. However, the state-of-the-art AR solution using head-mounted displays has not been widely accepted in clinical applications because it causes some inconvenience for the surgeon during surgery. METHODS: In this paper, we present a Tablet-AR system that transmits navigation information to a movable tablet PC via a wireless local area network and overlays this information on the tablet screen, which simultaneously displays the actual scene captured by its back-facing camera. With this system, the surgeon can directly observe the intracranial anatomical structure of the patient with the overlaid virtual projection images to guide the surgery. RESULTS: The alignment errors in the skull specimen study and clinical experiment were 4.6 pixels (approx. 1.6 mm) and 6 pixels (approx. 2.1 mm), respectively. The system was also used for navigation in 2 actual clinical cases of neurosurgery, which demonstrated its feasibility in a clinical application. CONCLUSIONS: The easy-to use Tablet-AR system presented in this study is accurate and feasible in clinical applications and has the potential to become a routine device in AR neuronavigation. PMID- 24216674 TI - Role of dialysis sodium gradient on intradialytic hypertension: an observational study. AB - INTRODUCTION: The causes of intradialytic hypertension (IDHyper) are not well understood and this condition can complicate the clinical management of hemodialysis (HD) patients. AIM: To evaluate the potential role of intradialytic sodium gradient (NaG) on blood pressure values and IDHyper during HD. PATIENTS AND METHODS: 206 prevalent HD patients on 3 times weekly HD treatment for at least 6 months (dialytic vintage 6-240 months) followed at our institution were studied. Mean age was 68 +/- 14 years, 129 were men. For 2 consecutive months (24 HD sessions) after the start of observation, the following variables were evaluated in predialysis after the long interdialysis interval: pre-HD plasma sodium (pNa, mmol/l) and potassium (pK, mmol/l) concentrations (mean value of 8 determinations), pre- and post-HD systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) blood pressure, dry body weight (dBW, kg), interdialytic weight gain (IDWG, kg), ultrafiltration rate (UFR, ml/kg/h), dialysis dose (Kt/V), protein catabolic rate (PCRn, g/kg/day), hemoglobin (Hb, g/dl). SBP, DBP, IDWG, UFR are the mean values of the 24 HD sessions. 76% of patients were on antihypertensive therapy, 171 patients were on bicarbonate HD, and 35 on HDF. Dialysate Na concentration was set at 140 mmol/l in all patients. Duration of HD and the blood and dialysate flow rate were kept constant during observation. STATISTICAL ANALYSIS: Data are expressed as mean +/- SD; linear and multiple regression analysis and t test for unpaired data were employed. Significant differences were defined as p < 0.05. RESULTS: Pre-HD pNa was 138.1 +/- 2.3 mmol/l, pK 5.0 +/- 0.4 mmol/l, dBW 67 +/- 14 kg, IDWG 2.9 +/- 0.8 kg, UFR 11.2 +/- 3.7 ml/kg/h, Kt/V 1.43 +/- 0.18, PCRn 1.13 +/- 0.17 g/kg/day, and Hb 11.2 +/- 0.8 g/dl. Pre- and post-HD SBP values were 139 +/- 13 and 134 +/- 12 mm Hg (p < 0.0001); pre- and post-HD DBP did not change significantly. A dialysis Na gradient (NaG) (dialysate Na - pre-HD pNa) was calculated, as well as the delta of SBP (DeltaSBP) (post-HD SBP - pre-HD SBP). IDHyper was defined as DeltaSBP >0. A significant direct correlation was found between NaG and DeltaSBP (p < 0.0001) and multiple regression analysis with DeltaSBP as dependent variable confirmed the strong correlation with NaG (p < 0.00001). According to DeltaSBP behavior, 171 patients (83%) had a decrease or no change in post-HD SBP (group 1; no IDHyper); 35 patients (17%) increased their post-HD SBP (group 2; IDHyper). NaG values were significantly greater in patients in group 2 (group 1: 1.5 +/- 2.2 vs. group 2: 3.3 +/- 2.5, p < 0.0001). CONCLUSIONS: This study shows that the intradialytic DeltaSBP is independently and strongly associated with the dialytic NaG. The more positive the NaG (net intradialytic Na gain), the more positive the DeltaSBP and IDHyper. PMID- 24216676 TI - Paediatric intraocular lens placement: how clear is the way forward? PMID- 24216675 TI - Clinical analysis of five methods used to treat condylomata acuminata. AB - OBJECTIVE: Treatments for condylomata acuminata (CA) include pharmacotherapy and surgical therapies, but each treatment has its limitations. The aim of this study was to investigate the virus clearance rate, wart cure rate and safety of 5 methods on CA. METHODS: 361 patients diagnosed with CA were divided into groups A (<0.5 cm), B (0.5-2.0 cm) and C (>2.0-4.0 cm) according to the maximum diameter of their lesion. Five treatments were compared in each group, and the clinical outcomes were evaluated during follow-ups. RESULTS: A 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is preferred if the maximum lesion diameter is <0.5 cm and an ALA-PDT plus cryotherapy treatment is preferred for lesions 0.5-2.0 cm. For lesions >2.0- 4.0 cm, an ALA-PDT retreatment (after cryotherapy or CO2 laser treatment) should be the first choice. CONCLUSIONS: The treatments for CA should be chosen according to the maximum diameter of each patient's lesion. PMID- 24216677 TI - Are preservatives necessary to improve efficacy of some glaucoma drops? PMID- 24216682 TI - 24-MHz scanner for optoacoustic imaging of skin and burn. AB - Optoacoustic (photoacoustic) imaging uniquely visualizes optical contrast in high resolution and comes with very attractive characteristics for clinical imaging applications. In this paper, we showcase the performance of a scanner based on a 24 MHz center-frequency 128 element array, developed for applications in dermatology. We perform system characterization to examine the imaging performance achieved. We then showcase its imaging ability on healthy tissue and cancer. Finally, we image burns and human lesions in vivo and gain insights on the benefits and challenges of this approach as it is considered for diagnostic and treatment follow-up applications in dermatology and beyond. PMID- 24216681 TI - Sparsity Constrained Mixture Modeling for the Estimation of Kinetic Parameters in Dynamic PET. AB - The estimation and analysis of kinetic parameters in dynamic positron emission tomography (PET) is frequently confounded by tissue heterogeneity and partial volume effects. We propose a new constrained model of dynamic PET to address these limitations. The proposed formulation incorporates an explicit mixture model in which each image voxel is represented as a mixture of different pure tissue types with distinct temporal dynamics. We use Cramer-Rao lower bounds to demonstrate that the use of prior information is important to stabilize parameter estimation with this model. As a result, we propose a constrained formulation of the estimation problem that we solve using a two-stage algorithm. In the first stage, a sparse signal processing method is applied to estimate the rate parameters for the different tissue compartments from the noisy PET time series. In the second stage, tissue fractions and the linear parameters of different time activity curves are estimated using a combination of spatial-regularity and fractional mixture constraints. A block coordinate descent algorithm is combined with a manifold search to robustly estimate these parameters. The method is evaluated with both simulated and experimental dynamic PET data. PMID- 24216683 TI - Theoretical comparison of the iodine quantification accuracy of two spectral CT technologies. AB - We compare the theoretical limits of iodine quantification for the photon counting multibin and dual energy technologies. Dual energy systems by necessity have to make prior assumptions in order to quantify iodine. We explicitly allow the multibin system to make the same assumptions and also allow them to be wrong. We isolate the effect of technology from imperfections and implementation issues by assuming both technologies to be ideal, i.e., without scattered radiation, unity detection efficiency and perfect energy response functions, and by applying the Cramer-Rao lower bound methodology to assess the quantification accuracy. When priors are wrong the maximum likelihood estimates will be biased and the mean square error of the quantification error is a more appropriate figure of merit. The evaluation assumes identical X-ray spectra for both methodologies and for that reason a sensitivity analysis is performed with regard to the assumed X ray spectrum. We show that when iodine is quantified over regions of interest larger than 6 cm(2), multibin systems benefit by independent estimation of three basis functions. For smaller regions of interest multibin systems can increase quantification accuracy by making the same prior assumptions as dual energy systems. PMID- 24216685 TI - Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. AB - BACKGROUND: The oral cavity is frequently affected in patients with inflammatory bowel disease (IBD), especially in patients with Crohn's disease (CD). Periodontitis is thought to influence systemic autoimmune or inflammatory diseases. We aimed to analyze the relationship of periodontitis and gingivitis markers with specific disease characteristics in patients with IBD and to compare these data with healthy controls. METHODS: In a prospective 8-month study, systematic oral examinations were performed in 113 patients with IBD, including 69 patients with CD and 44 patients with ulcerative colitis. For all patients, a structured personal history was taken. One hundred thirteen healthy volunteers served as a control group. Oral examination focussed on established oral health markers for periodontitis (bleeding on probing, loss of attachment, and periodontal pocket depth) and gingivitis (papilla bleeding index). Additionally, visible oral lesions were documented. RESULTS: Both gingivitis and periodontitis markers were higher in patients with IBD than in healthy control. In univariate analysis and logistic regression analysis, perianal disease was a risk factor for periodontitis. Nonsmoking decreased the risk of having periodontitis. No clear association was found between clinical activity and periodontitis in IBD. In only the CD subgroup, high clinical activity (Harvey-Bradshaw index > 10) was associated with 1 periodontitis marker, the loss of attachment at sites of maximal periodontal pocket depth. Oral lesions besides periodontitis and gingivitis were not common, but nevertheless observed in about 10% of patients with IBD. CONCLUSIONS: IBD, and especially perianal disease in CD, is associated with periodontitis. Optimal therapeutic strategies should probably focus on treating both local oral and systemic inflammation. PMID- 24216686 TI - Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group. AB - OBJECTIVE: Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution. DESIGN: Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells. RESULTS: A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohn's disease-like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohn's disease-like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti-tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious. CONCLUSION: The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon. PMID- 24216687 TI - Liver abscess in patients with underlying inflammatory bowel diseases. PMID- 24216688 TI - Risk factors for symptom relapse in collagenous colitis after withdrawal of short term budesonide therapy. AB - BACKGROUND: Oral budesonide has been proven effective in short- and long-term treatment of collagenous colitis; however, symptom relapse frequently occurs after drug withdrawal. The aim of this study was to identify the risk factors for symptom relapse in patients with collagenous colitis after withdrawal of short term budesonide therapy. METHODS: One hundred twenty-three patients from 4 randomized controlled studies who achieved clinical remission after short-term treatment with budesonide (9 mg/d) were analyzed, including 40 patients receiving subsequent budesonide maintenance therapy (6 mg/d) for 6 months and 83 patients without active maintenance treatment. Variables available for analysis were age, sex, baseline stool frequency, duration of diarrhea, collagenous band thickness, and lamina propria inflammation. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated by Cox proportional hazard model. RESULTS: The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5 per day (HR, 3.95; 95% CI, 1.08-14.39), history of diarrhea >12 months (HR, 1.77; 95% CI, 1.04-3.03), and the absence of budesonide maintenance therapy (HR, 2.71; 95% CI, 1.37-5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5 per day (56 versus 199 d, P = 0.024), as in those with history of diarrhea >12 months (56 versus 220 d, P = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 d, P = 0.005). CONCLUSIONS: Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, whereas budesonide maintenance therapy is a protective factor against symptom relapse. PMID- 24216689 TI - The burden of comedication among patients with inflammatory bowel disease. AB - BACKGROUND: Polypharmacy is of growing concern in the chronically ill, including individuals with inflammatory bowel disease (IBD). The authors aimed to describe the prevalence and predictors of non-IBD medication use and to compare drug use among individuals with and without IBD. METHODS: This cross-sectional study included members of health plans included in the Thomson Reuters MarketScan databases with continuous enrollment during 2009 and 2010. Patients with IBD were identified through diagnosis codes and IBD medication dispensings and matched to 5 individuals without IBD. The prevalences of dispensed prescriptions for analgesics (narcotics, nonnarcotics), psychiatric medications (anxiolytics/sedatives/hypnotics, antidepressants), and broad drug classes defined by the Anatomic Therapeutic Classification system were estimated. Predictors of non-IBD medication use and comparisons of drug use by IBD status were evaluated using logistic regression. RESULTS: The prevalence of medication use was higher among patients with IBD than matched members of the general population for nearly every drug class examined, including narcotic analgesics (48.1% versus 34.1%), nonnarcotic analgesics (12.8% versus 8.1%), anxiolytics/sedatives/hypnotics (25.8% versus 16.7%), and antidepressants (28.3% versus 19.4%). Medicaid insurance, middle age, gastrointestinal surgery, Crohn's disease, and increasing number of inpatient, and outpatient, and prescription events were significantly associated with analgesic and psychiatric medication use among patients with IBD. Psychiatric drug dispensings were more common among female IBD patients than male patients. CONCLUSIONS: Patients with IBD have increased medication use, particularly of analgesic and psychiatric drugs. IBD care providers should be aware of polypharmacy and its potential for drug interactions. PMID- 24216691 TI - Efficient separation of the orbital angular momentum eigenstates of light. AB - Orbital angular momentum (OAM) of light is an attractive degree of freedom for fundamental studies in quantum mechanics. In addition, the discrete unbounded state-space of OAM has been used to enhance classical and quantum communications. Unambiguous measurement of OAM is a key part of all such experiments. However, state-of-the-art methods for separating single photons carrying a large number of different OAM values are limited to a theoretical separation efficiency of about 77%. Here we demonstrate a method which uses a series of unitary optical transformations to enable the measurement of light's OAM with an experimental separation efficiency of >92%. Furthermore, we demonstrate the separation of modes in the angular position basis, which is mutually unbiased with respect to the OAM basis. The high degree of certainty achieved by our method makes it particularly attractive for enhancing the information capacity of multi-level quantum cryptography systems. PMID- 24216693 TI - Synthesis of crambescin B carboxylic acid, a potent inhibitor of voltage-gated sodium channels. AB - The stereocontrolled synthesis of a racemic carboxylic acid of crambescin B, a marine alkaloid, is described. The synthesis features two highly stereoselective reactions: (I) palladium-catalyzed hydroxymethylation of an alkynyl aziridine having an N-guanidino group and (II) cascade bromocyclization providing a spiro hemiaminal structure. The cell-based colorimetric assay showed that the synthesized carboxylic acid exhibited a potent inhibitory activity on voltage gated sodium channels. PMID- 24216694 TI - Fully automatic detection of deep white matter T1 hypointense lesions in multiple sclerosis. AB - A novel method is presented for fully automatic detection of candidate white matter (WM) T1 hypointense lesions in three-dimensional high-resolution T1 weighted magnetic resonance (MR) images. By definition, T1 hypointense lesions have similar intensity as gray matter (GM) and thus appear darker than surrounding normal WM in T1-weighted images. The novel method uses a standard classification algorithm to partition T1-weighted images into GM, WM and cerebrospinal fluid (CSF). As a consequence, T1 hypointense lesions are assigned an increased GM probability by the standard classification algorithm. The GM component image of a patient is then tested voxel-by-voxel against GM component images of a normative database of healthy individuals. Clusters (>=0.1 ml) of significantly increased GM density within a predefined mask of deep WM are defined as lesions. The performance of the algorithm was assessed on voxel level by a simulation study. A maximum dice similarity coefficient of 60% was found for a typical T1 lesion pattern with contrasts ranging from WM to cortical GM, indicating substantial agreement between ground truth and automatic detection. Retrospective application to 10 patients with multiple sclerosis demonstrated that 93 out of 96 T1 hypointense lesions were detected. On average 3.6 false positive T1 hypointense lesions per patient were found. The novel method is promising to support the detection of hypointense lesions in T1-weighted images which warrants further evaluation in larger patient samples. PMID- 24216695 TI - Clinical Significance of CK19 Negative Breast Cancer. AB - Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis. PMID- 24216696 TI - The Critical Impact of HIF-1a on Gastric Cancer Biology. AB - Hypoxia inducible factor-1 (HIF-1) monitors the cellular response to the oxygen levels in solid tumors. Under hypoxia conditions, HIF-1a protein is stabilized and forms a heterodimer with the HIF-1beta subunit. The HIF-1 complex activates the transcription of numerous target genes in order to adapt the hypoxic environment in human cancer cells. In gastric cancer patients, HIF-1a activation following extended hypoxia strongly correlates with an aggressive tumor phenotype and a poor prognosis. HIF-1a activation has been also reported to occur via hypoxia-independent mechanisms such as PI3K/AKT/mTOR signaling and ROS production. This article argues for the critical roles of HIF-1a in glucose metabolism, carcinogenesis, angiogenesis, invasion, metastasis, cell survival and chemoresistance, focusing on gastric cancer. PMID- 24216698 TI - Gastric cancer: current status of diagnosis and treatment. AB - Gastric cancer is the second leading cause of death from malignant disease worldwide and most frequently discovered in advanced stages. Because curative surgery is regarded as the only option for cure, early detection of resectable gastric cancer is extremely important for good patient outcomes. Therefore, noninvasive diagnostic modalities such as evolutionary endoscopy and positron emission tomography are utilized as screening tools for gastric cancer. To date, early gastric cancer is being treated using minimally invasive methods such as endoscopic treatment and laparoscopic surgery, while in advanced cancer it is necessary to consider multimodality treatment including chemotherapy, radiotherapy, and surgery. Because of the results of large clinical trials, surgery with extended lymphadenectomy could not be recommended as a standard therapy for advanced gastric cancer. Recent clinical trials had shown survival benefits of adjuvant chemotherapy after curative resection compared with surgery alone. In addition, recent advances of molecular targeted agents would play an important role as one of the modalities for advanced gastric cancer. In this review, we summarize the current status of diagnostic technology and treatment for gastric cancer. PMID- 24216697 TI - Integrin alpha5beta1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors. AB - Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about alpha5beta1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that alpha5beta1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, alpha5beta1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific alpha5beta1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors. PMID- 24216699 TI - Molecular targeted agents for gastric cancer: a step forward towards personalized therapy. AB - Gastric cancer (GC) represents a major cancer burden worldwide, and remains the second leading cause of cancer-related death. Due to its insidious nature, presentation is usually late and often carries a poor prognosis. Despite having improved treatment modalities over the last decade, for most patients only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and its signaling pathways, offers the hope of clinically significant promising advances for selected groups of patients. Patients with Her-2 overexpression or amplification have experienced benefit from the integration of monoclonal antibodies such as trastuzumab to the standard chemotherapy. Additionally, drugs targeting angiogenesis (bevacizumab, sorafenib, sunitinib) are under investigation and other targeted agents such as mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors are in preclinical or early clinical development. Patient selection and the development of reliable biomarkers to accurately select patients most likely to benefit from these tailored therapies is now key. Future trials should focus on these advances to optimize the treatment for GC patients. This article will review recent progress and current status of targeted agents in GC. PMID- 24216701 TI - Chemoprevention of lung cancer: prospects and disappointments in human clinical trials. AB - Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention-focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates) may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARgamma agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis-both to minimize toxicity and maximize efficacy. PMID- 24216702 TI - Carcinoma-associated fibroblasts are a promising therapeutic target. AB - Human carcinomas frequently exhibit significant stromal reactions such as the so called "desmoplastic stroma" or "reactive stroma", which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies. PMID- 24216700 TI - Mouse models of gastric cancer. AB - Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID- 24216703 TI - Mouse Genetic Models Reveal Surprising Functions of IkB Kinase Alpha in Skin Development and Skin Carcinogenesis. AB - Gene knockout studies unexpectedly reveal a pivotal role for IkB kinase alpha (IKKa) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikka heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKa deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikka floxed mice. On the other hand, transgenic mice overexpressing IKKa in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKa represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKa deletion mediated by a mutation, which generates a stop codon in the Ikka gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKa and Ikka mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKa in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside. PMID- 24216704 TI - Blood outgrowth endothelial cells increase tumor growth rates and modify tumor physiology: relevance for therapeutic targeting. AB - Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm3) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the oxygenation and subsequent radiation response of tumors. We surmise that these cells are preferentially stimulated to divide in the tumor microenvironment, thereby inducing the significant increase in tumor growth observed and that the use of injected BOECs could be a viable approach to modulate the tumor microenvironment for therapeutic gain. Conversely, agents or approaches to block their recruitment and integration of BOECs into primary or metastatic lesions may be an effective way to restrain cancer progression before or after other treatments are applied. PMID- 24216705 TI - Histologic and genetic advances in refining the diagnosis of "undifferentiated pleomorphic sarcoma". AB - Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term "malignant fibrous histiocytoma" being replaced by "UPS". In 2010 an analysis of multiple sarcoma expression databases using a 170 gene predictor, re-classified most MFH and "not-otherwise-specified" (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin like growth factor 1 (IGF-1), Peroxisome proliferator-activated receptor gamma (PPARgamma), Nerve growth factor beta (NGF beta) and Fibroblast growth factor receptor (FGFR). PMID- 24216706 TI - The role of the immune response in merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies. PMID- 24216707 TI - Vitamin d: pharmacokinetics and safety when used in conjunction with the pharmaceutical drugs used in cancer patients: a systematic review. AB - Vitamin D has reported anti-cancer and anti-inflammatory properties modulated through gene transcription and non-genomic signaling cascades. The purpose of this review was to summarize the available research on interactions and pharmacokinetics between vitamin D and the pharmaceutical drugs used in patients with cancer. Hypercalcemia was the most frequently reported side effect that occurred in high dose calcitriol. The half-life of 25(OH)D3 and/or 1,25(OH)2D3 was found to be impacted by cimetidine; rosuvastatin; prednisone and possibly some chemotherapy drugs. No unusual adverse effects in cancer patients; beyond what is expected from high dose 1,25(OH)2D3 supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH)2D3 during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D3 have not been studied. PMID- 24216708 TI - A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16). AB - The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20-30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting. PMID- 24216710 TI - Changes in Candida spp., mutans streptococci and lactobacilli following treatment of early childhood caries: a 1-year follow-up. AB - Early childhood caries (ECC) is closely related to high numbers of mutans streptococci, lactobacilli and Candida albicans. Oral colonization of these microorganisms was monitored in a prospective clinical study in order to investigate the effect of comprehensive treatment under general anesthesia and the sustainability of microbial changes. Saliva samples were collected from 50 healthy infants with ECC before and in regular intervals up to 12 months after treatment. Microorganisms were detected by cultivation on selective agars (CRT(r) bacteria and Sabouraud/CandiSelectTM) and scored. Additionally, plaque on upper front teeth and the dmft were recorded. Parents were repeatedly interviewed regarding the children's diet and oral hygiene, accompanied by corresponding advice. Plaque frequency and the numbers of mutans streptococci, lactobacilli and yeasts were significantly reduced as a result of treatment (p < 0.0001, Wilcoxon test). Nevertheless, this effect was not permanent. An ordinal regression model on the follow-up period revealed that the odds for bacteria and yeasts to reach a higher score increased linearly over time (p < 0.01) with an odds ratio of 2.244 per year. One third (34%) of the children developed new dentinal lesions within 1 year postoperatively. High scores of lactobacilli before treatment predicted caries relapse (p < 0.05). Nutritional and oral hygiene habits changed only slightly despite advising. Elimination and restoration of ECC lesions under general anesthesia proved to be an effective procedure in reducing cariogenic bacteria and yeasts. A satisfactory and sustainable success, however, could be achieved neither regarding microbiologic parameters nor with respect to the relapse rate. More suitable strategies are needed. PMID- 24216711 TI - Parental support for policy measures and school-based efforts to address weight based victimization of overweight youth. AB - BACKGROUND: Despite research documenting weight-based victimization (WBV) toward overweight youth in the school setting, little work has examined parental perceptions of this problem or potential policy strategies to help protect youth who are teased and bullied about their weight. This study assessed parental reports of WBV in youth and parental support for potential measures to address this problem, including implementation of school-based resources, policies, and state and federal laws. METHODS: A national sample of parents in the United States (N=919) completed an online questionnaire about their perceptions of WBV in the school setting, including whether or not their child had experienced or witnessed WBV. Parents were also asked the degree to which they would support potential policy strategies to address WBV in schools, including school-based policies and state and federal laws to address weight-based bullying in youth. RESULTS: Parents perceived overweight youth to be vulnerable to WBV at school, but less than half of parents perceived schools to be prepared to deal with instances of WBV. Parents (both with and without overweight children) agreed that schools should implement anti-bullying policies that include specific protections for students who are overweight or obese, increase resources available to youth who experience WBV at school, and promote awareness about this problem. Over two thirds of parents agreed that state anti-bullying laws should include specific protections against weight-related bullying. CONCLUSION: These findings indicate that there is substantial support from parents, both with and without overweight children, to implement a range of policy measures to address this WBV at the school, state, and federal level. PMID- 24216709 TI - Nanomaterials and autophagy: new insights in cancer treatment. AB - Autophagy represents a cell's response to stress. It is an evolutionarily conserved process with diversified roles. Indeed, it controls intracellular homeostasis by degradation and/or recycling intracellular metabolic material, supplies energy, provides nutrients, eliminates cytotoxic materials and damaged proteins and organelles. Moreover, autophagy is involved in several diseases. Recent evidences support a relationship between several classes of nanomaterials and autophagy perturbation, both induction and blockade, in many biological models. In fact, the autophagic mechanism represents a common cellular response to nanomaterials. On the other hand, the dynamic nature of autophagy in cancer biology is an intriguing approach for cancer therapeutics, since during tumour development and therapy, autophagy has been reported to trigger both an early cell survival and a late cell death. The use of nanomaterials in cancer treatment to deliver chemotherapeutic drugs and target tumours is well known. Recently, autophagy modulation mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as adjuvant in chemotherapy or in the development of cancer vaccines or as a potential anti-cancer agent. Herein, we summarize the effects of nanomaterials on autophagic processes in cancer, also considering the therapeutic outcome of synergism between nanomaterials and autophagy to improve existing cancer therapies. PMID- 24216713 TI - What is wrong with discharges against medical advice (and how to fix them). PMID- 24216712 TI - Differences in body composition between metabolically healthy obese and metabolically abnormal obese adults. AB - Potential differences in body composition between metabolically healthy obese (MHO) and metabolically abnormal obese (OA) adults were explored with 395 obese adults from the Pennington Center Longitudinal Study (18-68 years). Adults were classified as OA (>=2 risk factors: blood pressure >=130/85 mmHg; triglycerides >=150 mg dl(-1); high-density lipoprotein cholesterol: men <40, women <50 mg dl( 1); fasting glucose >=100 mg dl(-1); waist circumference: >=102 cm men, women >=88 cm) or MHO (<2 risk factors). Whole-body bone mineral density and content, percent body fat, fat mass, lean mass and trunk adipose tissue mass were measured with dual-energy X-ray absorptiometry. Visceral (VAT), subcutaneous (SAT) and total abdominal adipose tissue (TAT) were measured with computed tomography. Gender-specific general linear regression models were used to determine differences in body composition between MHO and OA controlling for age, race, smoking status and menopause status. In men, MHO had lower fat mass (kg and %), trunk adipose tissue, VAT, SAT, TAT and lean mass compared with OA. MHO women had lower fat mass (kg), lean mass, trunk adipose tissue, VAT and TAT when compared with OA women. In conclusion, OA and MHO cardiometabolic profiles are characterized by differences in body composition consistent between genders. PMID- 24216714 TI - Motion-aware mesh-structured trellis for correlation modelling aided distributed multi-view video coding. AB - A joint source-channel coding has attracted substantial attention with the aim of further exploiting the residual correlation residing in the encoded video signals for the sake of improving the reconstructed video quality. In our previous paper, a first-order Markov process model was utilized as an error concealment tool for exploiting the intra-frame correlation residing in the Wyner-Ziv (WZ) frame in the context of pixel-domain distributed video coding. In this contribution, we exploit the interview correlation with the aid of an interview motion search in distributed multi-view video coding (DMVC). Initially, we rely on the system architecture of WZ coding invoked for multiview video. Then, we construct a novel mesh-structured pixel-correlation model from the inter-view motion vectors and derive its decoding rules for joint source-channel decoding. Finally, we benchmark the attainable system performance against the existing pixel-domain WZ coding based DMVC scheme, where the classic turbo codec is employed. Our simulation results show that substantial bitrate reductions are achieved by employing the proposed motion-aware mesh-structured correlation modelling technique in a DMVC scheme. PMID- 24216715 TI - A two dimensional optical input to one dimensional serial pulse transformation using confocal reflectors. AB - An optical approach using confocal parabolic reflectors is used to transform 2D input data based on spatial position to a 1D sequenced serial string. The optical input data are set up as a 2D array. Individual channels are established between the input array and the final output detector, which reads the data as a time based serial data. The transformation is achieved by changing the optical path length associated with each pixel and its channel to the output detector. The 2D data can be images or individual sources but the light must be parallel. This paper defines how to establish the channels and the calculations required to achieve the desired transformation. PMID- 24216716 TI - Configuration-Transition-Based Connected-Component Labeling. AB - This paper proposes a new approach to label-equivalence-based two-scan connected component labeling. We use two strategies to reduce repeated checking-pixel work for labeling. The first is that instead of scanning image lines one by one and processing pixels one by one as in most conventional two-scan labeling algorithms, we scan image lines alternate lines, and process pixels two by two. The second is that by considering the transition of the configuration of pixels in the mask, we utilize the information detected in processing the last two pixels as much as possible for processing the current two pixels. With our method, any pixel checked in the mask when processing the current two pixels will not be checked again when the next two pixels are processed; thus, the efficiency of labeling can be improved. Experimental results demonstrated that our method was more efficient than all conventional labeling algorithms. PMID- 24216717 TI - Including the Size of Regions in Image Segmentation by Region-Based Graph. AB - Applying a fast over-segmentation algorithm to image and working on a region based graph (instead of the pixel-based graph) is an efficient approach to reduce the computational complexity of graph-based image segmentation methods. Nevertheless, some undesirable effects may arise if the conventional cost functions, such as Ncut, AverageCut, and MinCut, are employed for partitioning the region-based graph. This is because these cost functions are generally tailored to pixel-based graphs. In order to resolve this problem, we first introduce a new class of cost functions (containing Ncut and AverageCut) for graph partitioning whose corresponding suboptimal solution can be efficiently computed by solving a generalized eigenvalue problem. Then, among these cost functions, we propose one that considers the size of regions in the partitioning procedure. By simulation, the performance of the proposed cost function is quantitatively compared with that of the Ncut and AverageCut. PMID- 24216718 TI - Seamless view synthesis through texture optimization. AB - In this paper, we present a novel view synthesis method named Visto, which uses a reference input view to generate synthesized views in nearby viewpoints. We formulate the problem as a joint optimization of inter-view texture and depth map similarity, a framework that is significantly different from other traditional approaches. As such, Visto tends to implicitly inherit the image characteristics from the reference view without the explicit use of image priors or texture modeling. Visto assumes that each patch is available in both the synthesized and reference views and thus can be applied to the common area between the two views but not the out-of-region area at the border of the synthesized view. Visto uses a Gauss-Seidel-like iterative approach to minimize the energy function. Simulation results suggest that Visto can generate seamless virtual views and outperform other state-of-the-art methods. PMID- 24216719 TI - A Unified Methodology for Computing Accurate Quaternion Color Moments and Moment Invariants. AB - In this paper, a general framework for computing accurate quaternion color moments and their corresponding invariants is proposed. The proposed unified scheme arose by studying the characteristics of different orthogonal polynomials. These polynomials are used as kernels in order to form moments, the invariants of which can easily be derived. The resulted scheme permits the usage of any polynomial-like kernel in a unified and consistent way. The resulted moments and moment invariants demonstrate robustness to noisy conditions and high discriminative power. Additionally, in the case of continuous moments, accurate computations take place to avoid approximation errors. Based on this general methodology, the quaternion Tchebichef, Krawtchouk, Dual Hahn, Legendre, orthogonal Fourier-Mellin, pseudo Zernike and Zernike color moments, and their corresponding invariants are introduced. A selected paradigm presents the reconstruction capability of each moment family, whereas proper classification scenarios evaluate the performance of color moment invariants. PMID- 24216720 TI - Baseline predictors of adherence to positive airway pressure therapy for sleep apnea: a 10-year single-center observational cohort study. AB - BACKGROUND: Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea syndrome (OSAS). OBJECTIVES: The aim of the current study was to determine operational long-term adherence to PAP and its predictors. METHODS: In a retrospective single-center observational cohort study, we analyzed all patients referred to our center with suspected OSAS between November 2001 and November 2011. Baseline results and last follow-up data of each patient were analyzed. Kaplan-Meier estimates of adherence and Cox proportional hazard regression for age, gender, Epworth sleepiness scale (ESS) scores, body mass index, apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were performed. Evolution of adherence was analyzed in yearly cohorts comparing the proportion of patients discontinuing PAP within 6 and 12 months. RESULTS: Of 4,638 referrals, 2,187 confirmed OSAS patients started PAP, 297 (14%) were referred out to other centers to follow-up, 42 (2%) died, and 92 (5%) no longer needed PAP. Of 1,756 patients, the median follow-up was 36 months [95% confidence interval (CI) 33.6-37.8], and adherence at 1, 5 and 10 years was 74 (CI 71-75; n = 1,028), 55 (CI 53-58; n = 281) and 51% (CI 48-55; n = 10), respectively. Adherence is associated with ESS score [hazard ratio (HR) 0.60; CI 0.47-0.78], ODI (HR 0.50; CI 0.32-0.77) and AHI (HR 0.56; CI 0.37-0.85). In yearly cohorts according to inclusion date, the absconder rate at 6 and 12 months was 20 (CI 18 22) and 27% (CI 25-30) for the first 8 years and improved to 10 (CI 7-15) and 14% (CI 10-19) for the last 2 years, respectively. CONCLUSIONS: Long-term adherence to PAP in OSAS is associated with baseline measures of disease severity. After 2009, an improvement in the adherence rate was observed. PMID- 24216721 TI - Combined therapeutic effect of probucol and cilostazol on endothelial function in patients with silent cerebral lacunar infarcts and hypercholesterolemia: a preliminary study. AB - OBJECTIVE: This study evaluated the efficacy of combined therapy with probucol and cilostazol on endothelial function in silent lacunar cerebral infarcts (SLCI) and mild hypercholesterolemia. SUBJECTS AND METHODS: Flow-mediated vasodilatation (FMD) and nitroglycerin-induced vasodilatation (NMD) were measured before and after 4 weeks of combined therapy with probucol (500 mg/day) and cilostazol (200 mg/day) in 34 patients with a mean age of 72 +/- 7 years (range 57-80 years) with SLCI, mild hypercholesterolemia (low-density lipoprotein cholesterol >100 mg/dl) and impaired endothelial function (FMD <6%). Patients were randomly allocated to one of the following two treatment groups: (1) aspirin (100 mg/day) with behavioral modifications, such as diet and/or exercise therapy (A group or control group, n = 17), and (2) probucol and cilostazol treatment (PC group, n = 17), also with behavioral modifications. RESULTS: Although the baseline FMD was not different between the two treatment arms (2.7 +/- 1.5 vs. 2.6 +/- 1.5%, n.s.), the posttreatment FMD was significantly improved in the PC group (from 2.7 +/- 1.5 to 3.5 +/- 1.7%, p < 0.05) but not in the A group (from 2.6 +/- 1.5 to 2.9 +/- 1.4%, n.s.). No differences were observed between baseline and posttreatment NMD in either group. The effects of treatments on lipid profiles were more profound in the PC group. CONCLUSION: Combined treatment with probucol and cilostazol resulted in subacute improvement in FMD/endothelial function in patients with SLCI with mild hypercholesterolemia. This combination therapy has the potential to reduce the risk of cardiovascular events via improvements in endothelial function and lipid profiles. PMID- 24216723 TI - Maintaining a stationary laser footprint during angular scan in internal reflection experiments. AB - In internal-reflection metrology using prisms, the prism is usually mounted on a rotation/translation stage to enable adjusting angle and location of the laser footprint on the surface. If a visual inspection method is used to find the laser footprint, the task becomes impossible if invisible radiation in the near infrared is employed. In addition, it may be desirable to perform angular scan experiments with a stationary footprint on the surface during scans, or even to automatically probe specific points on an extended prism face for predetermined incidence angles. In this paper, a formulation is developed to determine the required translation along the prism face to allow maintaining the laser footprint stationary under a given rotation. A web-based app developed under the scope of this work demonstrates the applicability of the approach for silica, BK7 and SF2 glasses, in the wavelength range from 500 to 1500 nm and for an arbitrary geometry of the glass prism. PMID- 24216722 TI - Perceptions of African-American health professionals and community members on the participation of children and pregnant women in genetic research. AB - BACKGROUND: As genetic research gains more prominence in society, ethical concerns and the need for safeguards in the participation of children and pregnant women have increased. This study examined the perspectives of African American health professional and community members on genetic research involving children and pregnant women. METHODS: We used a mixed-methods approach to collect and analyze survey data and qualitative data from focus groups of community members and structured interviews of health professionals. RESULTS: We found that community members had significantly more favorable attitudes toward participation of children and pregnant women in genetic research than health professionals. Health professionals did not differ significantly from community members in their perceived understanding of genetic research. Emergent themes included limited knowledge of genetic research and distinction of biomedical research and clinical care, ethical concerns about confidentiality and potential harm, and the need to protect children and pregnant women. Participants expressed high interest and favorable attitude towards genetic research, despite limited genetic knowledge and concerns of potential harm to children and pregnant women. Some participants felt that genetic research findings could help dispel stigma and reduce discrimination, especially in mental illness. CONCLUSION: Findings suggest that the recruitment of participants into genetic research should directly address privacy and benefit concerns, and limited knowledge of physical and mental illness genetic research. There is a critical need to invest and engage racial/ethnic communities early, provide education on genetics, mental illness, and translate and share research findings with these communities. PMID- 24216724 TI - Quantum dot infrared photodetector with gated-mode design for mid-IR single photon detection. AB - A novel design for a quantum dot infrared photodetector (QDIP) is proposed based on avalanche multiplication and is expected to be used as a single photon detector at mid-IR. A high field multiplication region is added to a conventional QDIP in separate absorption, charge, and multiplication structures to intensify incoming photocurrent generated in the absorption region. The absorption region of the photodetector consists of quantum dot layers that are responsible for absorption of mid-IR wavelengths. Because of higher operation voltages in gated mode operation, resonant tunneling barriers are also included in the absorption region to prevent higher dark currents. The absorption region is designed for operation at lambda=8 MUm. During the gate pulse period, photo-generated electrons can trigger an avalanche and produce an output pulse. For this detector, the dark count rate (DCR) and single photon quantum efficiency (SPQE) are calculated at different temperatures. SPQE with peak of about 0.3 for T=50 K is obtained. For higher temperatures, about T=120 K, SPQE is very low due to the contribution of dark carriers generated in the quantum dot absorption region. PMID- 24216725 TI - Calibration-free sensor for pressure and H2O concentration in headspace of sterile vial using tunable diode laser absorption spectroscopy. AB - Tunable diode laser absorption measurements of pressure and H2O concentration in the headspace of vials using a distributed-feedback (DFB) diode laser near 1.4 MUm are reported. A H2O line located near 7161.41 cm(-1) is selected based on its strong absorption strength and isolation from interference of neighboring transitions. Direct absorption spectra of H2O are obtained for the measurement path as well as the reference path by scanning the laser wavelength. The pressure and H2O vapor concentration in the headspace of a vial are inferred from a differential absorption signal, which is the difference between the measured and the referenced absorbance spectra. This sensor is calibration-free and no purge gas is needed. The demonstrated capability would enable measurements of pressure and H2O concentration in the headspace of vials within 2.21% and 2.86%, respectively. A precision of 1.02 Torr and 390 ppm is found for the pressure and H2O concentration, respectively. A set of measurements for commercial freeze dried products are also performed to illustrate the usefulness of this sensor. PMID- 24216726 TI - Fracture mechanics of delamination defects in multilayer dielectric coatings. AB - During the fabrication of multilayer-dielectric (MLD) thin-film-coated optics, such as the diffraction gratings used in OMEGA EP's pulse compressors, acid piranha cleaning can lead to the formation of chemically induced delamination defects. We investigate the causes of these defects and describe a mechanism for the deformation and failure of the MLD coating in response to hydrogen peroxide in the cleaning solution. A fracture mechanics model is developed and used to calculate the crack path that maximizes the energy-release rate, which is found to be consistent with the characteristic fracture pattern observed in MLD coating delamination defects. PMID- 24216727 TI - Graded-size microlens array by the pyro-electrohydrodynamic continuous printing method. AB - In the present work, the pyro-electrohydrodynamic technique was used for the realization of tunable-size microlens arrays. Poly(methyl methacrylate) dissolved in different solvent mixtures was used as the polymeric material for the realization of the microstructures. By controlling the experimental parameters and in particular, the volume of the drop reservoir, graded-size square arrays of tens of microlenses with focal length in the range 1.5-3 mm were produced. Moreover, the optical quality and geometrical features were investigated by profilometric and interferometric analysis. PMID- 24216728 TI - Arc fusion splicing effects in large-mode-area single-mode ytterbium-doped fibers. AB - For the first time the effects of arc fusion splicing on the residual stress and refractive index of large-mode-area single-mode ytterbium-doped fibers (YDFs) are investigated using a state-of-the-art three-dimensional concurrent stress-index measurement method. The results, based on a commercially available fiber, describe a host of perturbations that decrease the core/cladding refractive index difference by as much as 1.74 * 10(-3) over an axial length of many hundreds of wavelengths. Simulations indicate that these perturbations result in an expansion of the mode-field-diameter by 39.6% and, based on the measured sample, result in an extra splice loss of 20.8%. The results of this investigation will be useful in the design and optimization of high-power all-fiber YDF lasers and amplifiers. PMID- 24216729 TI - Reduction of backreflection noise in resonator micro-optic gyro by integer period sampling. AB - In resonator micro-optic gyros (RMOGs), the interference between the backreflection light beam of one pathway and the signal light beam of the other pathway deteriorates the gyro output waveforms, resulting in severe reduction in the gyro's accuracy. In this paper, an integer period sampling (IPS) method is introduced to minimize the sampling error caused by backreflection in RMOG for the first time to our knowledge. The experimental results show that both the bias repeatability and the short-term bias stability become better when the IPS condition is satisfied. A bias stability of 0.41 degrees /s over one hour with an integration time of 10 s has been realized in a RMOG that employs a silica waveguide ring resonator. PMID- 24216730 TI - Nonlinear calibration for generalized fringe projection profilometry under large measuring depth range. AB - A mathematical description of the absolute surface height distribution in generalized fringe projection profilometry under large measuring depth range is presented. Based on least-squares polynomial fitting, a nonlinear calibration to determine the mapping between phase change and surface height is proposed by considering the unequal height arrangement of the projector and the camera. To solve surface height from phase change, an iteration method is brought forward. Experiments are implemented to demonstrate the validity of the proposed calibration and an accuracy of 0.3 mm for surface profile under 300 mm measuring depth can be achieved. PMID- 24216731 TI - Error analyses and calibration methods with accelerometers for optical angle encoders in rotational inertial navigation systems. AB - By rotating a strapdown inertial navigation system (INS) over one or more axes, a number of error sources originating from the employed sensors cancel out during the integration process. Rotary angle accuracy has an effect on the performance of rotational INS (RINS). The application of existing calibration methods based on gyroscope measurements is restricted by the structure of the inertial measurement unit (IMU) and scale factor stability of the gyroscope. The multireadhead method has problems in miniaturization and cost. Hence, optical angle encoder calibration methods using accelerometers are proposed, on the basis of navigation error and accuracy requirement analyses for a single-axis RINS. The test results show that the accuracy of calibration methods proposed is higher than 4 arcsec (1sigma). PMID- 24216732 TI - Correction for reflected sky radiance in low-altitude coastal hyperspectral images. AB - Low-altitude coastal hyperspectral imagery is sensitive to reflections of sky radiance at the water surface. Even in the absence of sun glint, and for a calm water surface, the wide range of viewing angles may result in pronounced, low frequency variations of the reflected sky radiance across the scan line depending on the solar position. The variation in reflected sky radiance can be obscured by strong high-spatial-frequency sun glint and at high altitude by path radiance. However, at low altitudes, the low-spatial-frequency sky radiance effect is frequently significant and is not removed effectively by the typical corrections for sun glint. The reflected sky radiance from the water surface observed by a low-altitude sensor can be modeled in the first approximation as the sum of multiple-scattered Rayleigh path radiance and the single-scattered direct-solar beam radiance by the aerosol in the lower atmosphere. The path radiance from zenith to the half field of view (FOV) of a typical airborne spectroradiometer has relatively minimal variation and its reflected radiance to detector array results in a flat base. Therefore the along-track variation is mostly contributed by the forward single-scattered solar-beam radiance. The scattered solar-beam radiances arrive at the water surface with different incident angles. Thus the reflected radiance received at the detector array corresponds to a certain scattering angle, and its variation is most effectively parameterized using the downward scattering angle (DSA) of the solar beam. Computation of the DSA must account for the roll, pitch, and heading of the platform and the viewing geometry of the sensor along with the solar ephemeris. Once the DSA image is calculated, the near-infrared (NIR) radiance from selected water scan lines are compared, and a relationship between DSA and NIR radiance is derived. We then apply the relationship to the entire DSA image to create an NIR reference image. Using the NIR reference image and an atmospheric spectral reflectance look-up table, the low spatial frequency variation of the water surface-reflected atmospheric contribution is removed. PMID- 24216733 TI - Coded apertures for x-ray scatter imaging. AB - We examine coding strategies for coded aperture scatter imagers. Scatter imaging enables tomography of compact regions from snapshot measurements. We present coded aperture designs for pencil and fan beam geometries, and compare their singular value spectra with that of the Radon transform and selected volume tomography. We show that under dose constraints scatter imaging improves conditioning over alternative techniques, and that specially designed coded apertures enable snapshot 1D and 2D tomography. PMID- 24216734 TI - Pulse compression to 14 fs by third-order dispersion control in a hybrid grating prism compressor. AB - A pulse compressor consisting of a fiber and a compact hybrid grating-prism dispersive delay line (DDL) is used to compress readily-available 140-fs pulses from a Ti:sapphire laser. We generate broadband pulses of up to 75 THz FWHM bandwidth in normally-dispersive single-mode conventional and photonic crystal fibers, with a potential of compression to 6 fs. Pulse dechirping in our hybrid DDL through second- and third-order dispersion (TOD) compensation results in 10* compression to 14 fs, limited by the bandwidth of the DDL transfer function and higher-order dispersion. The large tunability of the TOD of the hybrid DDL is shown. PMID- 24216735 TI - Generation of an azimuthally polarized beam with a metallic ring core fiber. AB - A fiber with a thin-metallic layer introduced between the central core and the cladding is proposed to lift the near-degeneracy of the modes TE01, TM01, and HE21. It can be used to obtain the pure mode TE01 as both the active and passive fibers. In the case of the active fiber, the fiber with the appropriate rare earth doping profile in the central core is presented as the gain medium of a fiber laser. The numerical results show that the pure mode TE01 (99.99%) can be obtained. In the case of the passive fiber, Gaussian light beams with suitable shift distance from the center core are coupled into the fiber. The results indicate that only the mode TE01 remains with the increasing propagation distance. PMID- 24216736 TI - Comparative analysis of numerical methods for the mode analysis of laser beams. AB - We present a comparative study of four numerical methods to detect the mode content of a laser beam from, at most, two intensity images. The techniques are compared regarding temporal effort, stability, and accuracy, using the example of three multimode optical fibers that differ in the number of supported modes. PMID- 24216737 TI - Shack-Hartmann mask/pupil registration algorithm for wavefront sensing in segmented mirror telescopes. AB - Shack-Hartmann wavefront sensing in general requires careful registration of the reimaged telescope primary mirror to the Shack-Hartmann mask or lenslet array. The registration requirements are particularly demanding for applications in which segmented mirrors are phased using a physical optics generalization of the Shack-Hartmann test. In such cases the registration tolerances are less than 0.1% of the diameter of the primary mirror. We present a pupil registration algorithm suitable for such high accuracy applications that is based on the one used successfully for phasing the segments of the Keck telescopes. The pupil is aligned in four degrees of freedom (translations, rotation, and magnification) by balancing the intensities of subimages formed by small subapertures that straddle the periphery of the mirror. We describe the algorithm in general terms and then in the specific context of two very different geometries: the 492 segment Thirty Meter Telescope, and the seven "segment" Giant Magellan Telescope. Through detailed simulations we explore the accuracy of the algorithm and its sensitivity to such effects as cross talk, noise/counting statistics, atmospheric scintillation, and segment reflectivity variations. PMID- 24216738 TI - Achromatic optical compensation using dispersion of uniaxial films for elimination of off-axis light leakage in a liquid crystal cell. AB - We propose an achromatic optical-compensation method using uniaxial films to eliminate the off-axis light leakage at the dark state in a homogeneously aligned liquid crystal cell. Three uniaxial films with different dispersion characteristics are used so that they can compensate each other to achieve achromatic effective phase retardation at off-axis. The retardation values are optimized with the aid of the Poincare sphere and through numerical research. A contrast ratio of higher than 2000?1 is predicted over the entire +/-60 degrees viewing cone for a homogeneously aligned LC cell with zero pretilt angle. PMID- 24216739 TI - Characterization of laser-driven shock waves in solids using a fiber optic pressure probe. AB - Measurement of laser-driven shock wave pressure in solid blocks of polymethyl methacrylate is demonstrated using fiber optic pressure probes. Three probes based on a fiber Fabry-Perot, fiber Bragg grating, and interferometric fiber tip sensor are tested and compared. Shock waves are generated using a high-power laser focused onto a thin foil target placed in close proximity to the test blocks. The fiber Fabry-Perot sensor appears capable of resolving the shock front with a rise time of 91 ns. The peak pressure is estimated, using a separate shadowgraphy measurement, to be 3.4 GPa. PMID- 24216740 TI - Unambiguous 3D measurement from speckle-embedded fringe. AB - This paper proposes a novel phase-shifting method for fast, accurate, and unambiguous 3D shape measurement. The basic idea is embedding a speckle-like signal in three sinusoidal fringe patterns to eliminate the phase ambiguity, but without reducing the fringe amplitude or frequency. The absolute depth is then recovered through a robust region-wise voting strategy relying on the embedded signal. Using the theoretical minimum of only three images, the proposed method greatly facilitates the application of phase shifting in time-critical conditions. Moreover, the proposed method is resistant to the global illumination effects, as the fringe patterns used are with a single high frequency. Based on the proposed method, we further demonstrate a real-time, high-precision 3D scanning system with an off-the-shelf projector and a commodity camera. PMID- 24216741 TI - Detection of single gold nanoparticles using spatial modulation spectroscopy implemented with a galvo-scanning mirror system. AB - The optical extinction of single nanoparticles can be sensitively detected by spatial modulation spectroscopy (SMS), where the particle is moved in and out of a tightly focused laser beam with a piezo-device. Here we show that high sensitivity can be obtained by modulating the beam with a galvo-mirror system, rather than by moving the sample. This work demonstrates an inexpensive method for making a SMS microscope, and shows how an existing laser scanning microscope can be adapted for SMS measurements. The galvo-mirror technique also allows SMS measurements to be performed in a liquid, which is difficult to do with piezo modulation. PMID- 24216742 TI - Optical alignment of pixelated 4f optical system using multiplexed filter. AB - Novel optical alignment techniques to perform precise alignment of a typical pixelated 4f optical system are presented in this paper. These techniques use optical multiplexed matched filters, which were designed using a simple, efficient iterative optimization algorithm, known as direct binary search. Three alignment challenges are identified: positioning, focusing, and magnification. The first two alignments were performed using the optical multiplexed matched filtering technique, and the last one was performed using a new optical arrangement. Experimental results of the new alignment techniques and a simple optical pattern recognition problem to demonstrate the benefits of the new alignment techniques are also presented. Two pixelated, electrically addressed spatial light modulators (128 * 128 pixels and one pixel width is 80 MUm) were used to represent the input and filter planes. The results clearly show that the new alignment techniques allow the 4f system to be aligned to a precision of 80 MUm in the x-y direction and 0.716 mm in the z direction. PMID- 24216743 TI - In-line polarizer used in all-0 degrees -splice resonator fiber-optic gyro. AB - A method to suppress the polarization-fluctuation-induced drift in a resonator fiber-optic gyro is proposed in this paper. By inserting one in-line polarizer whose polarization extinction ratio is 30 dB into a polarization-maintaining fiber resonator with 0 degrees polarization-axis splices, the unwanted resonance is introduced to high loss and therefore the ratio of the resonance height of the desired eigen-states of polarization (ESOP) to the unwanted ESOP is 74 dB theoretically; thus the polarization-fluctuation-induced drift is adequately suppressed. The new scheme has excellent operability and high temperature stability simultaneously. Compared to the resonator with twin 90 degrees polarization-axis rotated splices, this scheme does not need precise length difference control. This work is of great importance in the research on resonator integrated optic gyros. PMID- 24216744 TI - Effect of aberrations in a holographic system on reflecting volume Bragg gratings. AB - The effect of aberrations in the recording beams of a holographic setup is discussed regarding the deterioration of properties of a reflecting volume Bragg grating. Imperfect recording beams result in a spatially varying grating vector, which causes broadening, asymmetry, and washed out side lobes in the reflection spectrum as well as a corresponding reduction in peak diffraction efficiency. These effects are more significant for gratings with narrower spectral widths. PMID- 24216745 TI - Enhancing the chroma of pigmented polymers using antireflective surface structures. AB - In this paper we investigate how the color of a pigmented polymer is affected by reduction of the reflectance at the air-polymer interface. Both theoretical and experimental investigations show modified diffuse-direct reflectance spectra when the reflectance of the surface is lowered. Specifically it is found that the color change is manifested as an increase in chroma, leading to a clearer color experience. The experimental implementation is done using random tapered surface structures replicated in polymer from silicon masters using hot embossing. PMID- 24216746 TI - Interferometric filters for spectral discrimination in high-spectral-resolution lidar: performance comparisons between Fabry-Perot interferometer and field widened Michelson interferometer. AB - Thanks to wavelength flexibility, interferometric filters such as Fabry-Perot interferometers (FPIs) and field-widened Michelson interferometers (FWMIs) have shown great convenience for spectrally separating the molecule and aerosol scattering components in the high-spectral-resolution lidar (HSRL) return signal. In this paper, performance comparisons between the FPI and FWMI as a spectroscopic discrimination filter in HSRL are performed. We first present a theoretical method for spectral transmission analysis and quantitative evaluation on the spectral discrimination. Then the process in determining the parameters of the FPI and FWMI for the performance comparisons is described. The influences from the incident field of view (FOV), the cumulative wavefront error induced by practical imperfections, and the frequency locking error on the spectral discrimination performance of the two filters are discussed in detail. Quantitative analyses demonstrate that FPI can produce higher transmittance while the remarkable spectral discrimination is one of the most appealing advantages of FWMI. As a result of the field-widened design, the FWMI still performs well even under the illumination with large FOV while the FPI is only qualified for a small incident angle. The cumulative wavefront error attaches a great effect on the spectral discrimination performance of the interferometric filters. We suggest if a cumulative wavefront error is less than 0.05 waves RMS, it is beneficial to employ the FWMI; otherwise, FPI may be more proper. Although the FWMI shows much more sensitivity to the frequency locking error, it can outperform the FPI given a locking error less than 0.1 GHz is achieved. In summary, the FWMI is very competent in HSRL applications if these practical engineering and control problems can be solved, theoretically. Some other estimations neglected in this paper can also be carried out through the analytical method illustrated herein. PMID- 24216747 TI - Understanding medical care of transplant recipients through integrated registry and pharmacy claims data. AB - BACKGROUND: Limited data exist on medication use aside from immunosuppression among large samples of kidney transplant recipients. METHODS: We examined a novel database wherein Organ Procurement and Transplantation Network (OPTN) registry data were linked to records from a US pharmaceutical claims clearinghouse (2005 2010 claims) to examine pharmaceutical care at the first transplant anniversary (n = 16,157). We quantified the use of the following medication types within +/ 60 days of the first-year OPTN report according to estimated glomerular filtration rate (eGFR): antihypertensives, lipid-lowering, bone and mineral, and anemia treatments. Adjusted associations of medication use with eGFR and other clinical factors were quantified by multivariate logistic regression. RESULTS: Requirements for multiple antihypertensive agents rose with lower eGFR, with beta blockers comprising the most commonly used antihypertensive agent. The adjusted likelihood of vitamin D (adjusted odds ratio (aOR) 2.07, 95% CI 1.19-3.59) and especially erythrocyte-stimulating agents (aOR 19.94, 95% CI 7.01-56.00) rose in a graded manner to peak with eGFR <15 versus >90, whereas statin use was most common with eGFR 30-59 ml/min/1.73 m(2). Black race was independently associated with increased use of all classes of antihypertensives and vitamin D, but lower adjusted statin use. Rapamycin-based immunosuppression was associated with increased use of statins and erythrocyte-stimulating agents. CONCLUSIONS: Integrated registry and pharmacy fill data provide a novel tool for pharmacoepidemiologic investigations of delivered post-transplant care. Transplant recipients with reduced renal function have increased requirements for pharmaceutical care of comorbidities. Causes of racial variation in medication fills warrant further investigation. PMID- 24216748 TI - Decoding the patterns of ubiquitin recognition by ubiquitin-associated domains from free energy simulations. AB - Ubiquitin is a highly conserved, highly represented protein acting as a regulating signal in numerous cellular processes. It leverages a single hydrophobic binding patch to recognize and bind a large variety of protein domains with remarkable specificity, but can also self-assemble into chains of poly-diubiquitin units in which these interfaces are sequestered, profoundly altering the individual monomers' recognition characteristics. Despite numerous studies, the origins of this varied specificity and the competition between substrates for the binding of the ubiquitin interface patch remain under heated debate. This study uses enhanced sampling all-atom molecular dynamics to simulate the unbinding of complexes of mono- or K48-linked diubiquitin bound to several ubiquitin-associated domains, providing insights into the mechanism and free energetics of ubiquitin recognition and binding. The implications for the subtle tradeoff between the stability of the polyubiquitin signal and its easy recognition by target protein assemblies are discussed, as is the enhanced affinity of the latter for long polyubiquitin chains compared to isolated mono- or diubiquitin. PMID- 24216749 TI - Direct targeting of the thalamic anteroventral nucleus for deep brain stimulation by T1-weighted magnetic resonance imaging at 3 T. AB - BACKGROUND: The thalamic anteroventral nucleus (AV) is a promising target structure for deep brain stimulation (DBS) in patients suffering from refractory epilepsy. Direct visualization of the AV would improve spatial accuracy in functional stereotactic neurosurgery for treatment of this disease. METHODS: On 3 tesla magnetic resonance imaging (MRI), acquisition parameters were adjusted for optimal demarcation of the AV in 1 healthy subject. Reliability of AV visualization was then evaluated in 5 healthy individuals and 3 patients with refractory epilepsy. RESULTS: In all individuals, an adjusted T1-weighted sequence allowed for demarcation of the AV. It was clearly distinguishable from hyperintense myelin-rich lamellae surrounding it ventrally and laterally and appeared hypo-intense compared to the adjacent thalamic nuclei. Image resolution and contrast facilitated direct stereotactic targeting of the AV prior to DBS surgery in all 3 patients. CONCLUSIONS: Direct targeting of the AV can be achieved, which has immediate implications for the accuracy of MRI-guided DBS in patients with refractory epilepsy. PMID- 24216751 TI - Synchronization of EEG: bivariate and multivariate measures. AB - Synchronization behavior of electroencephalographic (EEG) signals is important for decoding information processing in the human brain. Modern multichannel EEG allows a transition from traditional measurements of synchronization in pairs of EEG signals to whole-brain synchronization maps. The latter can be based on bivariate measures (BM) via averaging over pair-wise values or, alternatively, on multivariate measures (MM), which directly ascribe a single value to the synchronization in a group. In order to compare BM versus MM, we applied nine different estimators to simulated multivariate time series with known parameters and to real EEGs.We found widespread correlations between BM and MM, which were almost frequency-independent for all the measures except coherence. The analysis of the behavior of synchronization measures in simulated settings with variable coupling strength, connection probability, and parameter mismatch showed that some of them, including S-estimator, S-Renyi, omega, and coherence, aremore sensitive to linear interdependences,while others, like mutual information and phase locking value, are more responsive to nonlinear effects. Onemust consider these properties together with the fact thatMM are computationally less expensive and, therefore, more efficient for the large-scale data sets than BM while choosing a synchronization measure for EEG analysis. PMID- 24216750 TI - Maternal immune activation increases the corticosterone response to acute stress without affecting the hypothalamic monoamine content and sleep patterns in male mice offspring. AB - BACKGROUND/AIMS: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. METHODS: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. RESULTS AND CONCLUSION: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring. PMID- 24216752 TI - Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. AB - Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and PAR4 reactivity and were inversely correlated with PCTP mRNA levels, PC-TP protein levels and PAR4 reactivity. miR 376c regulated the expression of PC-TP in human megakaryocytes. A disproportionately high number of microRNAs that were differentially expressed by race and PAR4 reactivity, including miR-376c, are encoded in the DLK1-DIO3 locus and were expressed at lower levels in platelets from black subjects. These results suggest that PC-TP contributes to the racial difference in PAR4-mediated platelet activation, indicate a genomic contribution to platelet function that differs by race and emphasize a need to consider the effects of race when developing anti-thrombotic drugs. PMID- 24216754 TI - Reaction site-driven regioselective synthesis of AChE inhibitors. AB - The enzyme-directed synthesis is an emerging fragment-based lead discovery approach in which the biological target is able to assemble its own multidentate ligands from a pool of building blocks. Here, we report for the first time the use of the human acetylcholinesterase (AChE) as an enzyme for the design and synthesis of new potent heterodimeric huprine-based inhibitors. Both the specific click chemistry site within the protein and the regioselectivity of the Huisgen cycloaddition observed suggest promising alternatives in the design of efficient mono- and dimeric ligands of AChE. Finally, a detailed computational modelling of the click reaction was conducted to further understand the origin of this TGS selectivity. PMID- 24216753 TI - Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs. AB - Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta3, beta5 or beta6 integrins or conditional loss of beta8 integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases. PMID- 24216755 TI - The discrepancy between patients and informants on clinician-rated measures in major depressive disorder: implications for clinical trials and clinical practice. AB - Clinician-rated measures are used in clinical trials and measurement-based clinical care settings to assess baseline symptoms and treatment outcomes of major depressive disorder (MDD), with a widely held dictum that they are sufficient in assessing the patient's clinical status. In this study, we examined clinician-rated measures of depressive and global symptom severity, obtained by interviewing patients as well as informants in an attempt to examine the potential difference or similarity between these two sources of information. The sample consisted of 89 treatment seeking, DSM-IV diagnosed MDD outpatients treated between 1995 and 2004. The clinician-rated measures used included the Montgomery Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI) for Severity. The scores of the clinician-rated measures collected from patients' interviews were compared with those collected from informants' interviews. Clinician-rated scores, collected by interviewing patients, were significantly higher and indicative of greater symptom severity when compared with those collected by interviewing informants. This was true for both the MADRS before (P<0.0001) and after treatment scores (P<0.0001), as well as the CGI before (P<0.0001) and after treatment scores (P<0.0001). Consistently involving informants and the time/burden it takes for them to participate might not be practical in MDD clinical trials or everyday clinical care. The discrepancies observed between the clinician-rated scores obtained from patients and informants emphasize the importance of incorporating collateral information during the assessment and rating of depressive symptom severity in both clinical trials as well as in clinical practice. PMID- 24216756 TI - Cheap glass fiber mats as a matrix of gel polymer electrolytes for lithium ion batteries. AB - Lithium ion batteries (LIBs) are going to play more important roles in electric vehicles and smart grids. The safety of the current LIBs of large capacity has been remaining a challenge due to the existence of large amounts of organic liquid electrolytes. Gel polymer electrolytes (GPEs) have been tried to replace the organic electrolyte to improve their safety. However, the application of GPEs is handicapped by their poor mechanical strength and high cost. Here, we report an economic gel-type composite membrane with high safety and good mechanical strength based on glass fiber mats, which are separator for lead-acid batteries. The gelled membrane exhibits high ionic conductivity (1.13 mS cm(-1)), high Li(+) ion transference number (0.56) and wide electrochemical window. Its electrochemical performance is evaluated by LiFePO4 cathode with good cycling. The results show this gel-type composite membrane has great attraction to the large-capacity LIBs requiring high safety with low cost. PMID- 24216757 TI - Increased air stability and decreased dehydrogenation temperature of LiBH4 via modification within poly(methylmethacrylate). AB - An air-stable LiBH4 polymeric composite was successfully prepared by modifying LiBH4 with a gas-barrier polymer matrix, poly(methylmethacrylate) (PMMA). The as prepared LiBH4@PMMA composite started to dehydrogenate at 53 degrees C with the first main dehydrogenation peak at 116 degrees C, and 5.2 wt% of hydrogen released at 162 degrees C within 1 h. PMID- 24216758 TI - The role of spacers on the self-assembly of DNA aptamer-amphiphiles into micelles and nanotapes. AB - The self-assembly of single-stranded DNA (ssDNA) aptamer-amphiphiles was influenced by the choice of spacer used to link the hydrophobic tail and aptamer headgroup. Aptamer-amphiphiles without spacers or with hydrophilic spacers formed globular micelles while amphiphiles with hydrophobic spacers formed bilayer nanotapes, which are the first such structures formed by DNA-amphiphiles. PMID- 24216759 TI - Receptor tyrosine kinase ubiquitylation involves the dynamic regulation of Cbl Spry2 by intersectin 1 and the Shp2 tyrosine phosphatase. AB - Ubiquitylation of receptor tyrosine kinases (RTKs) regulates their trafficking and lysosomal degradation. The multidomain scaffolding protein intersectin 1 (ITSN1) is an important regulator of this process. ITSN1 stimulates ubiquitylation of the epidermal growth factor receptor (EGFR) through enhancing the activity of the Cbl E3 ubiquitin ligase. However, the precise mechanism through which ITSN1 enhances Cbl activity is unclear. Here, we demonstrate that ITSN1 interacts with and recruits the Shp2 tyrosine phosphatase to Spry2 to enhance its dephosphorylation, thereby disrupting the inhibitory effect of Spry2 on Cbl and enhancing EGFR ubiquitylation. In contrast, expression of a catalytically inactive Shp2 mutant reversed the effect of ITSN1 on Spry2 dephosphorylation and decreased Cbl-mediated EGFR ubiquitylation. In addition, disruption of ITSN1 binding to Spry2 through point mutation of the Pro-rich ITSN1 binding site in Spry2 resulted in decreased Shp2-Spry2 interaction and enhanced Spry2 tyrosine phosphorylation. This study demonstrates that ITSN1 enhances Cbl activity, in part, by modulating the interaction of Cbl with Spry2 through recruitment of Shp2 phosphatase to the Cbl-Spry2 complex. These findings reveal a new level of complexity in the regulation of RTKs by Cbl through ITSN1 binding with Shp2 and Spry2. PMID- 24216760 TI - Beta-like importins mediate the nuclear translocation of mitogen-activated protein kinases. AB - The rapid nuclear translocation of signaling proteins upon stimulation is important for the regulation of de novo gene expression. We have studied the stimulated nuclear shuttling of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein kinases (MAPKs) and found that they translocate into the nucleus in a Ran-dependent, but NLS- or NTS-independent, manner, unrelated to their catalytic activity. We show that this translocation involves three beta like importins, importins 3, 7, and 9 (Imp3/7/9). Knockdown of these importins inhibits the nuclear translocation of the MAPKs and, thereby, activation of their transcription factor targets. We further demonstrate that the translocation requires the stimulated formation of heterotrimers composed of Imp3/Imp7/MAPK or Imp3/Imp9/MAPK. JNK1/2 and p38alpha/beta bind to either Imp7 or Imp9 upon stimulated posttranslational modification of the two Imps, while Imp3 joins the complex after its stimulation-induced phosphorylation. Once formed, these heterotrimers move to the nuclear envelope, where importin 3 remains, while importins 7 and 9 escort the MAPKs into the nucleus. These results suggest that beta-like importins are central mediators of stimulated nuclear translocation of signaling proteins and therefore add a central level of regulation to stimulated transcription. PMID- 24216762 TI - An investigation of the effects of the core protein telomerase reverse transcriptase on Wnt signaling in breast cancer cells. AB - Telomerase canonically maintains telomeres, but recent reports have suggested that the core protein mammalian telomerase reverse transcriptase (TERT) component, together with the chromatin remodeling factor BRG1 and beta-catenin, may also bind to and promote expression of Wnt target genes. However, this proposed noncanonical role of TERT in Wnt signaling has been controversial. Here, we investigated the effects of human TERT (hTERT) on Wnt signaling in human breast cancer lines and HeLa cells. We failed to find evidence for physical association of hTERT with BRG1 or beta-catenin; instead, we present evidence that anti-FLAG antibody cross-reactivity properties may explain the previously reported interaction of hTERT with beta-catenin. Furthermore, altering hTERT levels in four different breast cancer cell lines caused minimal and discordant effects on Wnt target and Wnt pathway gene expression. Although hTERT's role in Wnt signaling was addressed only indirectly, no significant representation of Wnt target genes was detected in chromatin immunoprecipitation-sequencing (ChIP-seq) and chromatin isolation by RNA purification and sequencing (ChIRP-seq) loci cooccupied in HeLa S3 cells by both BRG1 and hTR. In summary, our evidence fails to support the idea of a biologically consistent hTERT interaction with the Wnt pathway in human breast cancer cells, and any detectable influence of hTERT depended on cell type and experimental system. PMID- 24216761 TI - Identification of a novel protein interaction motif in the regulatory subunit of casein kinase 2. AB - Casein kinase 2 (CK2) regulates multiple cellular processes and can promote oncogenesis. Interactions with the CK2beta regulatory subunit of the enzyme target its catalytic subunit (CK2alpha or CK2alpha') to specific substrates; however, little is known about the mechanisms by which these interactions occur. We previously showed that by binding CK2beta, the Epstein-Barr virus (EBV) EBNA1 protein recruits CK2 to promyelocytic leukemia (PML) nuclear bodies, where increased CK2-mediated phosphorylation of PML proteins triggers their degradation. Here we have identified a KSSR motif near the dimerization interface of CK2beta as forming part of a protein interaction pocket that mediates interaction with EBNA1. We show that the EBNA1-CK2beta interaction is primed by phosphorylation of EBNA1 on S393 (within a polyserine region). This phosphoserine is critical for EBNA1-induced PML degradation but does not affect EBNA1 functions in EBV replication or segregation. Using comparative proteomics of wild-type (WT) and KSSR mutant CK2beta, we identified an uncharacterized cellular protein, C18orf25/ARKL1, that also binds CK2beta through the KSSR motif and show that this involves a polyserine sequence resembling the CK2beta binding sequence in EBNA1. Therefore, we have identified a new mechanism of CK2 interaction used by viral and cellular proteins. PMID- 24216763 TI - Pknox1/Prep1 regulates mitochondrial oxidative phosphorylation components in skeletal muscle. AB - The homeodomain transcription factor Prep1 was previously shown to regulate insulin sensitivity. Our aim was to study the specific role of Prep1 for the regulation of energy metabolism in skeletal muscle. Muscle-specific ablation of Prep1 resulted in increased expression of respiratory chain subunits. This finding was consistent with an increase in mitochondrial enzyme activity without affecting mitochondrial volume fraction as assessed by electron microscopy. Metabolic phenotyping revealed no differences in daily energy expenditure or body composition. However, during treadmill exercise challenge, Prep1 ablation resulted in a higher maximal oxidative capacity and better endurance. Elevated PGC-1alpha expression was identified as a cause for increased mitochondrial capacity in Prep1 ablated mice. Prep1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1alpha activity. Thereby, p160 protein levels were significantly lower in the muscle of Prep1 ablated mice. By a chromatin immunoprecipitation-sequencing (ChIP-seq) approach, PREP1 binding sites in genes encoding mitochondrial components (e.g., Ndufs2) were identified that might be responsible for elevated proteins involved in oxidative phosphorylation (OXPHOS) in the muscle of Prep1 null mutants. These results suggest that Prep1 exhibits additional direct effects on regulation of mitochondrial proteins. We therefore conclude that Prep1 is a regulator of oxidative phosphorylation components via direct and indirect mechanisms. PMID- 24216764 TI - p300-dependent acetylation of activating transcription factor 5 enhances C/EBPbeta transactivation of C/EBPalpha during 3T3-L1 differentiation. AB - Adipogenesis is a multistep process by which 3T3-L1 preadipocytes differentiate into mature adipocytes through mitotic clonal expansion (MCE) and terminal differentiation. The CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important transcription factor that takes part in both of these processes. C/EBPbeta not only transactivates C/EBPalpha and the peroxisome proliferator activated receptor gamma (PPARgamma), which cause 3T3-L1 preadipocytes to enter terminal adipocyte differentiation, but also is required to activate cell cycle genes necessary for MCE. The identification of potential cofactors of C/EBPbeta will help to explain how C/EBPbeta undertakes these specialized roles during the different stages of adipogenesis. In this study, we found that activating transcription factor 5 (ATF5) can bind to the promoter of C/EBPalpha via its direct interaction with C/EBPbeta (which is mediated via the p300-dependent acetylation of ATF5), leading to enhanced C/EBPbeta transactivation of C/EBPalpha. We also show that p300 is important for the interaction of ATF5 with C/EBPbeta as well as for the binding activity of this complex on the C/EBPalpha promoter. Consistent with these findings, overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. Furthermore, we show that the elevated expression of ATF5 is correlated with an obese phenotype in both mice and humans. In summary, we have identified ATF5 as a new cofactor of C/EBPbeta and examined how C/EBPbeta and ATF5 (acetylated by a p300-dependent mechanism) regulate the transcription of C/EBPalpha. PMID- 24216765 TI - Characterization of the embB gene in Mycobacterium tuberculosis isolates from Barcelona and rapid detection of main mutations related to ethambutol resistance using a low-density DNA array. AB - OBJECTIVES: Ethambutol resistance has mostly been related to mutations in the embB gene. The objective of the present study was to characterize the embB gene in a collection of ethambutol-resistant and ethambutol-susceptible isolates of Mycobacterium tuberculosis complex (MTBC) from Barcelona, and to develop a DNA microarray for the rapid detection of embB mutations in our area. METHODS: Fifty three ethambutol-resistant and 702 ethambutol-susceptible isolates of MTBC were sequenced in internal 982-1495 bp fragments of the embB gene. In addition, a low cost, low-density array was designed to include the embB codons identified as being most frequently mutated in our area (LD-EMB array). RESULTS: The global prevalence of embB mutations found among the ethambutol-resistant isolates was 77.4% (41/53). Substitutions in embB306 were the most common [53.7% (22/41)], followed by substitutions in embB406 [26.8% (11/41)]. The presence of mutations in embB406 was related to higher levels of ethambutol resistance and to multidrug resistance. Among unrelated isolates (from 24-locus MIRU-VNTR genotyping), the percentage of embB-mutated isolates was 72.9% (27/37)--59.3% (16/27) in embB306 and 25.9% (7/27) in embB406. None of the ethambutol-susceptible isolates studied showed a mutation in codon 306 or 406. The LD-EMB array showed 100% sensitivity and specificity in identifying the main embB substitutions in our area. CONCLUSIONS: Mutations at codons 306 and 406 of embB have a relevant role in resistance to ethambutol in our area. The LD-EMB array developed in this study would appear to be a good molecular test for rapid detection of ethambutol resistance. PMID- 24216766 TI - Antibacterial activity of bone cement containing quaternary ammonium polyethyleneimine nanoparticles. PMID- 24216767 TI - Correlation between veterinary antimicrobial use and antimicrobial resistance in food-producing animals: a report on seven countries. AB - OBJECTIVES: To evaluate correlations between antimicrobial use and the prevalence of resistance in commensal Escherichia coli isolates from pigs, poultry and cattle, using data from publicly available national or international reports from seven European countries. METHODS: The link between the quantities of different classes of antimicrobials administered to food-producing animals per country (expressed in mg/population correction unit) and the prevalence of resistance to the different antimicrobial classes (interpreted by EUCAST epidemiological cut off values) in E. coli isolates (4831 isolates in total) was assessed by means of polynomial regression analysis and determination of Spearman's rank correlation coefficient. RESULTS: A quadratic regression best fitted the antimicrobial use and antimicrobial resistance data. The coefficient of determination was, in decreasing order, 0.99 for fluoroquinolones and amphenicols, 0.94 for third generation cephalosporins and sulphonamides, 0.93 for aminopenicillins, 0.86 for fluoroquinolones, 0.81 for streptomycin and 0.80 for gentamicin and tetracycline. Spearman's rank correlation coefficient was 1 for amphenicols, 0.96 for sulphonamides, 0.93 for streptomycin and tetracycline, 0.89 for aminopenicillins, 0.71 for gentamicin and 0.70 for third-generation cephalosporins. CONCLUSIONS: These remarkably high coefficients indicate that, at a national level, the level of use of specific antimicrobials strongly correlates to the level of resistance towards these agents in commensal E. coli isolates in pigs, poultry and cattle. However, data restraints reveal the need for further detail in collection and harmonization of antimicrobial resistance and use data in Europe. PMID- 24216768 TI - Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene. AB - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to beta-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin-binding protein (PBP) 2a that has a low affinity to beta-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA. We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to pencillinase-resistant beta-lactam antibiotics. METHODS: The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays. RESULTS: We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which may be the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types. CONCLUSIONS: This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for beta lactam resistance in MRSA that may need to be considered by diagnostic laboratories. PMID- 24216769 TI - Pancreatitis in tigecycline Phase 3 and 4 clinical studies. AB - OBJECTIVES: To examine the incidence of pancreatitis among subjects enrolled in the tigecycline clinical trial programme, summarize cases and examine concomitant use of other pancreatitis-causing medications. METHODS: Subject data from Phase 3 and 4 comparative tigecycline studies were included in the analysis; investigator reported adverse events of 'pancreatitis', 'necrotizing pancreatitis' or 'pancreas disorder' were reviewed. Data were summarized and cases were reported. No statistical comparisons were made. The incidence of overall pancreatitis with 95% CIs was calculated. The Wilson score method was used to calculate CIs. RESULTS: Nineteen subjects with investigator-determined pancreatitis were identified from the programme database, which included 3788 subjects treated with tigecycline and 3646 subjects treated with a comparator. There were 9 cases identified among the tigecycline-treated subjects [9 of 3788 (0.24%; 95% CI, 0.11 0.45)] and 10 cases among the comparator-treated subjects [10 of 3646 (0.27%; 95% CI, 0.13-0.50)]. The demographic characteristics of the subjects with pancreatitis were similar between treatment groups. The median duration of tigecycline therapy was 8.0 days compared with 11.0 days of comparator treatment. Concomitant or prior exposure to a Badalov class I medication was evident in the majority of subjects who developed pancreatitis. A numerically higher number of tigecycline-treated subjects were exposed to furosemide prior to the onset of pancreatitis than comparator-treated subjects. CONCLUSIONS: Pancreatitis was uncommon in subjects treated with tigecycline, with an occurrence of <1%. Concomitant medications known to cause pancreatitis should be considered when prescribing tigecycline, but may not identify those at risk of developing pancreatitis. PMID- 24216771 TI - Laboratory and field study of the potential benefits of pinna cue-preserving hearing aids. AB - The potential benefits of preserving high-frequency spectral cues created by the pinna in hearing-aid fittings were investigated in a combined laboratory and field test. In a single-blind crossover design, two settings of an experimental hearing aid were compared. One setting was characterized by a pinna cue preserving microphone position, whereas the other was characterized by a microphone position not preserving pinna cues. Participants were allowed 1 month of acclimatization to each setting before measurements of localization and spatial release from speech-on-speech masking were completed in the laboratory. Real-world experience with the two settings was assessed by means of questionnaires. Seventeen participants with mild to moderate sensorineural hearing impairments completed the study. An inconsistent pinna cue benefit pattern was observed across the outcome measures. In the localization test, the pinna cue-preserving setting provided a significant mean reduction of 22 degrees in the root mean square (RMS) error in the front-back dimension, with 13 of the 17 participants showing a reduction of at least 15 degrees . No significant mean difference in RMS error between settings was observed in the left-right dimension. No significant differences between settings were observed in the spatial-unmasking test conditions. The questionnaire data indicated a small, but nonsignificant, benefit of the pinna cue-preserving setting in certain real-life situations, which corresponded with a general preference for that setting. No significant real-life localization benefit was observed. The results suggest that preserving pinna cues can offer benefit in some conditions for individual hearing aid users with mild to moderate hearing loss and is unlikely to harm performances for the rest. PMID- 24216772 TI - Asynchronous binaural spatial audition sensor with 2 * 64 * 4 channel output. AB - This paper proposes an integrated event-based binaural silicon cochlea system aimed at efficient spatial audition and auditory scene analysis. The cochlea chip has a matched pair of digitally-calibrated 64-stage cascaded analog second-order filter banks with 512 pulse-frequency modulated (PFM) address-event representation (AER) outputs. The quality factors (Qs) of channels are individually adjusted by local DACs. The 2P4M 0.35 um CMOS chip consumes an average power of 14 mW including its integrated microphone preamplifiers and biasing circuits. Typical speech data rates are 10 k to 100 k events per second (eps) with peak output rates of 10 Meps. The event timing jitter is 2 us for a 250 mVpp input. It is shown that the computational cost of an event-driven source localization application can be up to 40 times lower when compared to a conventional cross-correlation approach. PMID- 24216773 TI - Association between dental caries and adiposity status (general, central, and peripheral adiposity) in 12-year-old children. AB - BACKGROUND/AIMS: To investigate the cross-sectional relationship between dental caries experience and adiposity status (general, central, and peripheral adiposity) in 12-year-old children in Hong Kong. METHODS: A random sample of 668 12-year-old students was recruited. Clinical assessment for dental caries (DMFT) was conducted using WHO criteria. Anthropometric measurements for body height, body weight, waist circumference (WC), hip circumference and triceps skinfold thickness (TRSKF) were performed to assess general adiposity (weight-height ratio, body mass index); central adiposity (WC; waist-hip ratio, WHR), and peripheral adiposity (TRSKF). Associations between adiposity indices and dental caries experience [prevalence DMFT > 0, 'high' experience (DMFT >= SiC Index value) and 'very high' experience (DMFT >= SiC10 Index value)] were examined in bivariate and multivariate regression analyses. RESULTS: The response rate was 76.9% (n = 514/668). Regression analyses (adjusted for oral hygiene practice, snacking habits, and socio-demographic factors) identified that WHR z score was associated with 'high' dental caries experience (OR 1.33, 95% CI 1.05, 1.70, p = 0.02), and that WHR z score was associated with 'very high' dental caries experience (OR 1.52, 95% CI 1.10, 2.11, p = 0.01). TRSKF z score was associated with 'very high' dental caries experience (OR 1.47, 95% CI 1.10, 1.96, p = 0.01). CONCLUSIONS: In a population-based sample of 12-year-old children in Hong Kong, dental caries experience was associated with adiposity. Central and peripheral, but not general adiposity was associated with dental caries experience. PMID- 24216774 TI - Experimental and numerical assessment of low-frequency current distributions from UMTS and GSM mobile phones. AB - The evaluation of the exposure from mobile communication devices requires consideration of electromagnetic fields (EMFs) over a broad frequency range from dc to GHz. Mobile phones in operation have prominent spectral components in the low-frequency (LF) and radio-frequency (RF) ranges. While the exposure to RF fields from mobile phones has been comprehensively assessed in the past, the LF fields have received much less attention. In this study, LF fields from mobile phones are assessed experimentally and numerically for the global system for mobile (GSM) and universal mobile telecommunications system (UMTS) communication systems and conclusions about the global (LF and RF) EMF exposure from both systems are drawn. From the measurements of the time-domain magnetic fields, it was found that the contribution from the audio signal at a normal speech level, i.e., -16 dBm0, is the same order of magnitude as the fields induced by the current bursts generated from the implementation of the GSM communication system at maximum RF output level. The B-field induced by currents in phones using the UMTS is two orders of magnitude lower than that induced by GSM. Knowing that the RF exposure from the UMTS is also two orders of magnitude lower than from GSM, it is now possible to state that there is an overall reduction of the exposure from this communication system. PMID- 24216775 TI - Real-time detection of an airborne microorganism using inertial impaction and mini-fluorescent microscopy. AB - To achieve successful real-time detection of airborne pathogenic microorganisms, the problem must be considered in terms of their physical size and biological characteristics. We developed an airborne microorganism detection chip to realize the detection of microorganisms, ensuring compactness, sensitivity, cost efficiency, and portability, using three key components: an inertial impaction system, a cartridge-type impaction plate, and a mini-fluorescent microscope. The inertial impaction system was used to separate microorganisms in terms of their aerodynamic particle size, and was fabricated with three impaction stages. Numerical analysis was performed to design the system; the calculated cutoff diameter at each impaction stage was 2.02 (first stage), 0.88 (second stage), and 0.54 MUm (third stage). The measured cutoff diameters were 2.24, 0.91, and 0.49 MUm, respectively. A cartridge-type impaction plate was used, composed of molded polydimethylsiloxane (PDMS) and an actual impaction region made of a SYBR green I dye-stained agar plate. A mini-fluorescent microscope was used to distinguish microbes from non-biological particles. Images of the microorganisms deposited at the impaction zone were obtained via mini-fluorescent microscopy, and fluorescent intensities of the images were calculated using in-house image-processing software. The results showed that the developed system successfully identified aerosolized biological particles from non-biological particles in real time. PMID- 24216776 TI - Trends in the incidence of childhood type 1 diabetes mellitus in Beijing based on hospitalization data from 1995 to 2010. AB - OBJECTIVES: To study the incidence trend of type 1 diabetes mellitus (T1DM) in children in Beijing from 1995 to 2010, to compare it with incidences reported worldwide and to predict the requirement of medical resources in the future. METHODS: This study involved newly diagnosed T1DM cases younger than 15 years of age in the Beijing Children's Hospital from January 1995 to December 2010. We calculated the incidence of T1DM children in Beijing according to hospitalization data and Beijing's population. We defined it as the underestimated incidence rate (UE-IR). RESULTS: The UE-IRs of T1DM ranged from around 0.88/100,000 to 2.37/100,000 for children in Beijing younger than 15 years of age from 1995 to 2010. The UE-IR increased faster in boys (1.47 times) and in the age group of 0-4 years (1.89 times) after 2003. The UE-IR was greatest in children aged 5-9 years (1.81/100,000) followed by the age of puberty (10-14 years, 1.76/100,000). The predicted number of new T1DM cases in Beijing will increase 1.97 times over the next 10 years. CONCLUSIONS: The incidence trend of T1DM was increasing gradually in those younger than 15 years of age in Beijing. The incidence of younger children and boys grew faster. The 5- to 14-year-old children represented a high risk population of T1DM. The number of predicted new T1DM cases will grow rapidly. This means that we should train more health care providers for pediatric diabetes patients, in order to achieve high-quality medical care and to be able to prevent or postpone chronic complications. PMID- 24216777 TI - Effecting professional unity. PMID- 24216781 TI - GRowing an epidermal tumor. AB - The glucocorticoid receptor (GR), a member of the nuclear hormone family of transcription factors, has key physiological roles in many organs, including the skin. In this issue, Latorre et al. demonstrate that mice lacking GR in the epidermis exhibit increased vulnerability to chemical carcinogenesis. Evidence supporting an involvement of GR signaling in physiological and pathophysiological processes in skin is discussed. PMID- 24216782 TI - Oral CCR5 inhibitors to prevent HIV transmission: the new "morning-before pill"? AB - In a recent study by Matsuzawa and colleagues, Maraviroc, a CCR5 inhibitor, was used as pre-exposure prophylaxis against HIV-1 infection. The authors used an ex vivo model of HIV transmission to study the distribution and effectiveness of this HIV inhibitor in healthy volunteers. Strikingly, 3 days or more of oral administration of Maraviroc to healthy volunteers conferred protection against HIV infection to skin-derived Langerhans cells in the ex vivo system, suggesting Maraviroc as a useful candidate for pre-exposure prophylaxis in clinical trials. PMID- 24216786 TI - Small interfering RNA. PMID- 24216787 TI - Ultrabroadband nonreciprocal transverse energy flow of light in linear passive photonic circuits. AB - Using a technique, analogous to coherent population trapping in an atomic system, we propose schemes to create transverse light propagation violating left-right symmetry in a photonic circuit consisting of three coupled waveguides. The frequency windows for the symmetry breaking of the left-right energy flow span over 80 nm. Our proposed system only uses linear passive optical materials and is easy to integrate on a chip. PMID- 24216788 TI - High resolution imaging with differential infrared absorption micro-spectroscopy. AB - Although confocal infrared (IR) absorption micro-spectroscopy is well established for far-field chemical imaging, its scope remains restricted since diffraction limits the spatial resolution to values a little above half the radiation wavelength. Yet, the successful implementations of below-the-diffraction limit far-field fluorescence microscopies using saturated irradiation patterns for example for stimulated-emission depletion and saturated structured-illumination suggest the possibility of using a similar optical patterning strategy for infrared absorption mapping at high resolution. Simulations are used to show that the simple mapping of the difference in transmitted/reflected IR energy between a saturated vortex-shaped beam and a Gaussian reference with a confocal microscope affords the generation of high-resolution vibrational absorption images. On the basis of experimentally relevant parameters, the simulations of the differential absorption scheme reveal a spatial resolution better than a tenth of the wavelength for incident energies about a decade above the saturation threshold. The saturated structured illumination concepts are thus expected to be compatible with the establishment of point-like point-spread functions for measuring the absorbance of samples with a scanning confocal microscope recording the differential transmission/reflection. PMID- 24216789 TI - Indirect absorption spectroscopy using quantum cascade lasers: mid-infrared refractometry and photothermal spectroscopy. AB - We record vibrational spectra with two indirect schemes that depend on the real part of the index of refraction: mid-infrared refractometry and photothermal spectroscopy. In the former, a quantum cascade laser (QCL) spot is imaged to determine the angles of total internal reflection, which yields the absorption line via a beam profile analysis. In the photothermal measurements, a tunable QCL excites vibrational resonances of a molecular monolayer, which heats the surrounding medium and changes its refractive index. This is observed with a probe laser in the visible. Sub-monolayer sensitivities are demonstrated. PMID- 24216790 TI - High-resolution microscopy for biological specimens via cathodoluminescence of Eu and Zn-doped Y2O3 nanophosphors. AB - High-resolution microscopy for biological specimens was performed using cathodoluminescence (CL) of Y(2)O(3):Eu, Zn nanophosphors, which have high CL intensity due to the incorporation of Zn. The intensity of Y(2)O(3):Eu nanophosphors at low acceleration voltage (3 kV) was increased by adding Zn. The CL intensity was high enough for imaging even with a phosphor size as small as about 30 nm. The results show the possibility of using CL microscopy for biological specimens at single-protein-scale resolution. CL imaging of HeLa cells containing laser-ablated Y(2)O(3):Eu, Zn nanophosphors achieved a spatial resolution of a few tens of nanometers. Y(2)O(3):Eu, Zn nanophosphors in HeLa cells were also imaged with 254 nm ultraviolet light excitation. The results suggest that correlative microscopy using CL, secondary electrons and fluorescence imaging could enable multi-scale investigation of molecular localization from the nanoscale to the microscale. PMID- 24216791 TI - All-optical phase discrimination using SOA. AB - We describe the first experimental demonstration of a novel all-optical phase discrimination technique, which can separate the two orthogonal phase components of a signal onto different frequencies. This method exploits nonlinear mixing in a semiconductor optical amplifier (SOA) to separate a 10.65 Gbaud QPSK signal into two 10.65 Gb/s BPSK signals which are then demodulated using a delay interferometer (DI). Eye diagrams and spectral measurements verify correct operation and a conversion efficiency greater than 9 dB is observed on both output BPSK channels when compared with the input QPSK signal. PMID- 24216792 TI - Investigation of spherical aberration effects on coherent lidar performance. AB - In this paper we demonstrate experimentally the performance of a monostatic coherent lidar system under the influence of phase aberrations, especially the typically predominant spherical aberration (SA). The performance is evaluated by probing the spatial weighting function of the lidar system with different telescope configurations using a hard target. It is experimentally and numerically proven that the SA has a significant impact on lidar antenna efficiency and optimal beam truncation ratio. Furthermore, we demonstrate that both effective probing range and spatial resolution of the system are substantially influenced by SA and beam truncation. PMID- 24216793 TI - Grating-based x-ray phase-contrast imaging with a multi energy-channel photon counting pixel detector. AB - We have carried out grating-based x-ray differential phase-contrast measurements with a hybrid pixel detector in 16 energy channels simultaneously. A method for combining the energy resolved phase-contrast images based on energy weighting is presented. An improvement in contrast-to-noise ratio by 58.2% with respect to an emulated integrating detector could be observed in the final image. The same image quality could thus be achieved with this detector and with energy weighting at 60.0% reduced dose compared to an integrating detector. The benefit of the method depends on the object, spectrum, interferometer design and the detector efficiency. PMID- 24216794 TI - Properties of nonlinear noise in long, dispersion-uncompensated fiber links. AB - We study the properties of nonlinear interference noise (NLIN) in fiber-optic communications systems with large accumulated dispersion. Our focus is on settling the discrepancy between the results of the Gaussian noise (GN) model (according to which NLIN is additive Gaussian) and a recently published time domain analysis, which attributes drastically different properties to the NLIN. Upon reviewing the two approaches we identify several unjustified assumptions that are key in the derivation of the GN model, and that are responsible for the discrepancy. We derive the true NLIN power and verify that the NLIN is not additive Gaussian, but rather it depends strongly on the data transmitted in the channel of interest. In addition we validate the time-domain model numerically and demonstrate the strong dependence of the NLIN on the interfering channels' modulation format. PMID- 24216795 TI - Photonic-assisted multi-channel compressive sampling based on effective time delay pattern. AB - In this paper, a photonic-assisted multi-channel compressive sampling scheme is proposed with one pseudo-random binary sequence (PRBS) source and Wavelength Division Multiplexing-based time delay. Meanwhile, the restricted isometry property of sensing matrix determined by the optimized time delay pattern is analyzed. In experiment, a four-channel photonic-assisted system with 5-GHz bandwidth was set up, where four-channel PRBS signals were generated by adding fiber-induced constant time delays to four-wavelength modulated PRBS signal, and a signal composed of twenty tones was recovered faithfully with four analog-to digital converters (ADCs) with only 120-MHz-bandwidth. PMID- 24216796 TI - Yb:YAl3(BO3)4 as gain material in thin-disk oscillators: demonstration of 109 W of IR output power. AB - The first demonstration of an Yb:YAl3(BO3)4 thin-disk laser is reported. An output power of 109 W with an optical efficiency of 50.2% was achieved in multimode CW-operation which is to the best of our knowledge a significant record performance compared to previous reports on CW-lasers with this material. At a lower power level of 19.3 W the material proved its suitability for efficient operation with an optical efficiency of 60.4%. In fundamental-mode operation the extracted output power was 10.4 W with an optical efficiency of 44.5% and a beam propagation factor M(2) = 1.39. The broad emission bandwidth of the material was confirmed by measuring a continuous wavelength tuning range from 1001 to 1053 nm with a maximum output power of 36 W at 1040 nm. PMID- 24216797 TI - Unified approach to Cerenkov second harmonic generation. AB - We discuss the effect of second harmonic generation via the Cerenkov-like process in nonlinear bulk media and waveguides. We show that in both schemes the Cerenkov harmonic emission represents in fact a nonlinear Bragg diffraction process. It is therefore possible, for the first time, to describe the bulk and waveguide Cerenkov emission uniformly by considering the spatial modulation of the second order nonlinear polarization. This is also experimentally illustrated by studying the Cerenkov second harmonic generation at the boundary of a nonlinear quadratic medium via the total internal reflection inside the nonlinear crystal. PMID- 24216798 TI - Silicon based polarization insensitive filter for WDM-PDM signal processing. AB - We propose and fabricate a novel circuit that combines two two-dimensional (2D) grating couplers and a microring resonator (MRR). According to the polarization states, one 2D grating coupler first splits the input signals into two orthogonal paths, which co-propagate in the loop and share a common MRR, and then the two paths are combined together by the other 2D grating coupler. The proposed circuit is polarization insensitive and can be used as a polarization insensitive filter. For demonstration, the wavelength division and polarization division multiplexing (WDM-PDM) non return-to-zero differential-phase-shift-keying (NRZ-DPSK) signals can be demodulated successfully. The bit error ratio measurements show an error free operation, reflecting the good performance and the practicability. PMID- 24216799 TI - High-sensitive and broad-dynamic-range quantitative phase imaging with spectral domain phase microscopy. AB - Spectral domain phase microscopy for high-sensitive and broad-dynamic-range quantitative phase imaging is presented. The phase retrieval is realized in the depth domain to maintain a high sensitivity, while the phase information obtained in the spectral domain is exploited to extend the dynamic range of optical path difference. Sensitivity advantage of phase retrieved in the depth domain over that in the spectral domain is thoroughly investigated. The performance of the proposed depth domain phase based approach is illustrated by phase imaging of a resolution target and an onion skin. PMID- 24216800 TI - Controllable chrominance and highly improved luminescent quantum yield of YV(1 x)P(x)O4: Tm, Dy, Eu inverse opal white light phosphors. AB - In this work, rare earth (RE) ions tri-doped YV(1-x)P(x)O(4): RE(3+) (RE = Tm, Dy, Eu) inverse opal photonic crystals (IOPCs) were fabricated by the PMMA template method, which demonstrated efficient white light emissions under ultraviolet excitation. It is significant to observe that the chrominance of the white light could be largely modulated by the photonic stop band of the IOPCs. And more, the photoluminescence quantum yield in the IOPCs was largely improved over the grinded reference (REF) because the undesired energy transfer (ET) process was effectively restrained. PMID- 24216801 TI - Two-mode PLC-based mode multi/demultiplexer for mode and wavelength division multiplexed transmission. AB - We proposed a PLC-based mode multi/demultiplexer (MUX/DEMUX) with an asymmetric parallel waveguide for mode division multiplexed (MDM) transmission. The mode MUX/DEMUX including a mode conversion function with an asymmetric parallel waveguide can be realized by matching the effective indices of the LP(01) and LP(11) modes of two waveguides. We report the design of a mode MUX/DEMUX that can support C-band WDM-MDM transmission. The fabricated mode MUX/DEMUX realized a low insertion loss of less than 1.3 dB and high a mode extinction ratio that exceeded 15 dB. We used the fabricated mode MUX/DEMUX to achieve a successful 2 mode x 4 wavelength x 10 Gbps transmission over a 9 km two-mode fiber with a penalty of less than 1 dB. PMID- 24216802 TI - Optical caustics associated with the primary rainbow of oblate droplets: simulation and application in non-sphericity measurement. AB - A vector ray tracing (VRT) model is developed to simulate optical caustic structures in the primary rainbow region of light scattering from oblate droplets. The changes of the optical caustic structures in response to shape deformation of oblate droplets are investigated. Then the curvature calculated from the simulated rainbow fringes is compared with that from the measured rainbow fringes and good agreement is found. Furthermore, according to the generalized rainbow patterns and the relation between aspect ratio and curvature of the rainbow fringe, non-sphericities in terms of aspect ratio of an oblate water droplet is measured with high measurement accuracy. PMID- 24216803 TI - All-optical 10 Gb/s AND logic gate in a silicon microring resonator. AB - An all-optical AND logic gate in a single silicon microring resonator is experimentally demonstrated at 10 Gb/s with 50% RZ-OOK signals. By setting the wavelengths of two intensity-modulated input pumps on the resonances of the microring resonator, field-enhanced four-wave mixing with a total input power of only 8.5 dBm takes place in the ring, resulting in the generation of an idler whose intensity follows the logic operation between the pumps. Clear and open eye diagrams with a bit-error- ratio below 10(-9) are achieved. PMID- 24216804 TI - Linear array of InAs APDs operating at 2 um. AB - A linear array of avalanche photodiodes (APDs) comprising of 128 pixels was fabricated from InAs. The uniformity of the dark currents and avalanche gain was investigated at 77, 200 K and room temperature. The array shows highly uniform results apart from some defective pixels at the edge of the arrays. At 200 K and at a wavelength of 2.04 um, we obtained an unmultiplied responsivity of 0.61 A/W at 0 V, along with a gain of 8.5 at a bias of 10 V. PMID- 24216805 TI - Flexible bandwidth DGD estimation for coherent optical OFDM system. AB - A Stokes vector based non-data-aided (NDA) differential group delay (DGD) estimation scheme with flexible bandwidth requirements is investigated. The scheme is demonstrated in both experiments and simulations for 40-Gb/s polarization-multiplexed coherent optical OFDM systems with up to 1000-km long haul transmission with an estimation error of less than 2.5 ps after 1000-km standard single-mode fiber transmissions. PMID- 24216806 TI - Engineering of metal-clad optical nanocavity to optimize coupling with integrated waveguides. AB - We propose a cladding engineering method that flexibly modifies the radiation patterns and rates of metal-clad nanoscale optical cavity. Optimally adjusting the cladding symmetry of the metal-clad nanoscale optical cavity modifies the modal symmetry and produces highly directional radiation that leads to 90% coupling efficiency into an integrated waveguide. In addition, the radiation rate of the cavity mode can be matched to its absorption rate by adjusting the thickness of the bottom-cladding layer. This approach optimizes the energy-flow rate from the waveguide and maximizes the energy confined inside the nanoscale optical cavity. PMID- 24216807 TI - Development of a simple system for simultaneously measuring 6DOF geometric motion errors of a linear guide. AB - A simple method for simultaneously measuring the 6DOF geometric motion errors of the linear guide was proposed. The mechanisms for measuring straightness and angular errors and for enhancing their resolution are described in detail. A common-path method for measuring the laser beam drift was proposed and it was used to compensate the errors produced by the laser beam drift in the 6DOF geometric error measurements. A compact 6DOF system was built. Calibration experiments with certain standard measurement meters showed that our system has a standard deviation of 0.5 um in a range of +/- 100 um for the straightness measurements, and standard deviations of 0.5", 0.5", and 1.0" in the range of +/- 100" for pitch, yaw, and roll measurements, respectively. PMID- 24216808 TI - Multi sky-view 3D aerosol distribution recovery. AB - Aerosols affect climate, health and aviation. Currently, their retrieval assumes a plane-parallel atmosphere and solely vertical radiative transfer. We propose a principle to estimate the aerosol distribution as it really is: a three dimensional (3D) volume. The principle is a type of tomography. The process involves wide angle integral imaging of the sky on a very large scale. The imaging can use an array of cameras in visible light. We formulate an image formation model based on 3D radiative transfer. Model inversion is done using optimization methods, exploiting a closed-form gradient which we derive for the model-fit cost function. The tomography model is distinct, as the radiation source is unidirectional and uncontrolled, while off-axis scattering dominates the images. PMID- 24216809 TI - Use of quasi-local photorefractive response to generated superficial self-written waveguides in lithium niobate. AB - We report the formation of surface self-written waveguides by means of surface pyrolitons in lithium niobate. By a specific orientation of the crystal axis the quasi-local slow photorefractive response of lithium niobate was used to induce a self-confined beam exactly at the crystal-air interface. The mode profile of the photo-induced waveguide is strongly asymmetric due to the interface presence. PMID- 24216810 TI - Folded dipole plasmonic resonators. AB - A class of folded ordered plasmonic dipole nanoresonators based on insulator metal-insulator (IMI) slab waveguides is proposed and studied. This work is motivated by the development of a novel fabrication process that avoids the need for direct write nanolithography and instead relies on accessible UV lithography and other top-down parallel fabrication techniques that result in metallic dolmen structures with nanometre sized gaps. In this context, the dolmen geometry consists of two vertical segments supporting a flat horizontal slab. It is shown using frequency domain finite element analysis that such structures, which are essentially folded dipole antennas, resonate in a similar manner to their linear unfolded counterparts. The effect of the likely fabrication features is also studied. PMID- 24216811 TI - Super-resolution compressive imaging with anamorphic optics. AB - A new imaging technique that combines compressive sensing and super-resolution techniques is presented. Compressive sensing is accomplished by capturing optically a set of Radon projections. Super-resolution measurements are simply taken by introducing a slanted two-dimensional array in the optical system. The goal of the technique is to overcome resolution limitation that occurs in imaging scenarios where dense pixels sensors with large number of pixels are not available or cannot be used. With the presented imaging technique, owing to the compressive sensing approach, we were able to reconstruct images with significantly more number of pixels than measured, and owing to the super resolution design we have been able to achieve resolution significantly beyond that limited by the sensor's pixels size. PMID- 24216812 TI - Efficient UV generation of a Yb-fiber MOPA producing high peak power for pulse durations of from 100 ps to 2 ns. AB - We demonstrate an average ultraviolet (UV) power generation of 20 W by harmonically converting the output of an all-fiber master oscillator power amplifier (MOPA) system. The third-harmonic generation (THG) UV output provides a conversion efficiency of 40% from the amplified fundamental output. The seed source, which consists of a 1064-nm-wavelength continuous-wave laser diode and two cascaded intensity modulators, produces chirp-free pulses with tunable durations from 100 ps to 2 ns at arbitrary repetition rates and a high dynamic extinction ratio. The fiber MOPA system generates a maximum average power of 50 W and a maximum peak power of 83 kW. PMID- 24216813 TI - InGaAs Schottky barrier diode array detector for a real-time compact terahertz line scanner. AB - We present a terahertz (THz) broadband antenna-integrated 1 * 20 InGaAs Schottky barrier diode (SBD) array detector with an average responsivity of 98.5 V/W at a frequency of 250 GHz, which is measured without attaching external amplifiers and Si lenses, and an average noise equivalent power (NEP) of 106.6 pW/?Hz. The 3-dB bandwidth of the SBD detector is also investigated at approximately 180 GHz. For implementing an array-type SBD detector by a simple fabrication process to achieve a high yield, a structure comprising an SiN(x) layer instead of an air bridge between the anode and the cathode is designed. THz line beam imaging using a Gunn diode emitter with a center frequency of 250 GHz and a 1 * 20 SBD array detector is successfully demonstrated. PMID- 24216814 TI - 200 W Diffraction limited, single-polarization, all-fiber picosecond MOPA. AB - A fully fiberized, single-polarization, gain-switched diode-seeded fiber master oscillator power amplifier (MOPA) system is demonstrated delivering 28 ps pulses at variable repetition frequencies ranging from 53 MHz up to 858 MHz. An average signal output power of 200 W was achieved with good OSNR for all operating frequencies. A maximum pulse energy of 3.23 MUJ at a repetition frequency of 53 MHz was achieved, corresponding to a pulse peak power of 107 kW. The extraction of higher pulse energy was limited primarily by the onset of nonlinear effects such as SRS which lead to compromised pulse quality at higher peak powers. PMID- 24216815 TI - Quantitative control over the intensity and phase of light transmitted through highly scattering media. AB - We experimentally demonstrate the use of the transmission matrix (TM) to quantitatively control the amplitude and phase of the light transmitted through highly scattering media. This is achieved by measuring the absolute value of the TM elements. We also use the fact that the cross-correlations between the contributions of different input channels at the observation plane is important in describing the transmitted optical field. In addition, we demonstrate both quantitative control of the intensity at multiple output spatial modes, each with a different intensity, as well as a "dark" area of low intensity. Our experiments are carried out using a low cost (less than US$600) spatial binary amplitude modulator that we modify for phase-only operation, as well as a novel optical setup that enables independent control of a reference and control signal while maintaining interferometric stability. The optical implementation used in this paper will make such experiments widely accessible to many researchers. Furthermore, the results presented could serve as the foundation for many useful potential applications ranging from the biomedical sciences to optical communications. PMID- 24216816 TI - InP-based waveguide photodiodes heterogeneously integrated on silicon-on insulator for photonic microwave generation. AB - High-linearity modified uni-traveling carrier photodiodes on silicon-on-insulator with low AM-to-PM conversion factor are demonstrated. The devices deliver more than 2.5 dBm RF output power up to 40 GHz and have an output third order intercept point of 30 dBm at 20 GHz. Photodiode arrays exceed a saturation current-bandwidth-product of 630 mA . GHz and reach unsaturated RF output power levels of 10 dBm at 20 GHz. PMID- 24216817 TI - Generation of blue light at 426 nm by frequency doubling with a monolithic periodically poled KTiOPO4. AB - Continuous-wave (cw) blue laser generation at 426 nm by frequency doubling with a monolithic periodically poled KTP (PPKTP) cavity is reported in this paper. Without any free mirrors, the standing-wave cavity solely consists of a monolithic PPKTP crystal, and both ends of which are spherically polished and mirror-coated. An output power of 158 mW is obtained when the pump power is 350 mW. The conversion efficiency is 45%. The dependence of the conversion efficiency on the temperature and the incident fundamental power has been discussed. Such a system is integrally stable and compact for long-time operation under temperature control. The system is much more stable than the usual servo lock system for external cavity doubling. PMID- 24216818 TI - Helical optical projection tomography. AB - A new technique termed Helical Optical Projection Tomography (hOPT) has been developed with the aim to overcome some of the limitations of current 3D optical imaging techniques. hOPT is based on Optical Projection Tomography (OPT) with the major difference that there is a translation of the sample in the vertical direction during the image acquisition process, requiring a new approach to image reconstruction. Contrary to OPT, hOPT makes possible to obtain 3D-optical images of intact long samples without imposing limits on the sample length. This has been tested using hOPT to image long murine tissue samples such as spinal cords and large intestines. Moreover, 3D-reconstructed images of the colon of DSS treated mice, a model for Inflammatory Bowel Disease, allowed the identification of the structural alterations. Finally, the geometry of the hOPT device facilitates the addition of a Selective Plane Illumination Microscopy (SPIM) arm, providing the possibility of delivering high resolution images of selected areas together with complete volumetric information. PMID- 24216819 TI - Simulation of a metallic SNOM tip illuminated by a parabolic mirror. AB - We investigate numerically a Scanning Near field Optical Microscope (SNOM) that uses a Parabolic Mirror (PM) to focus a radially polarized beam on a metallic tip. In order to overcome problems--like overestimated near fields or resonances- that arise when only considering finite tips, we have introduced a semi-infinite continuation of the tip, which incorporates the analytic solution of surface waves. For a realistic modeling the right description of the incident field is essential and we have complied with this requirement by a Bessel expansion of the focal fields, which is also applicable to an aplanatic objective. The established numerical model is used for an extensive study of model parameters like tip geometry, illumination directions and tip materials (Ag, Au, Al and Cu). Compared with a simplified inverted microscope configuration, the PM setup shows an increased field enhancement (factor of 2-2.5), which can be ascribed to the efficient coupling of the exciting field to tip surface plasmons. PMID- 24216820 TI - Parametric amplification and phase preserving amplitude regeneration of a 640 Gbit/s RZ-DPSK signal. AB - We report the first experimental demonstration of parametric amplification and all-optical phase-preserving amplitude regeneration for a 640 Gbit/s return-to zero (RZ) differential phase-shift keying (DPSK) optical time division multiplexed (OTDM) signal. In the designed gain-flattened single-pump fiber optical parametric amplifier (FOPA), 620 fs short optical pulses are successfully amplified with 15 dB gain with error-free performance and less than 1 dB power penalty. Phase-preserving amplitude regeneration based on gain saturation in the FOPA is carried out for optical signals with degraded optical signal-to-noise ratio. An improvement of 2.2 dB in receiver sensitivity at a bit-error-ratio of 10(-9) has been successfully achieved after regeneration, together with 13.3 dB net gain. PMID- 24216821 TI - Performance and capacity analysis of Poisson photon-counting based Iter-PIC OCDMA systems. AB - In this paper, an iterative parallel interference cancellation (Iter-PIC) technique is developed for optical code-division multiple-access (OCDMA) systems relying on shot-noise limited Poisson photon-counting reception. The novel semi analytical tool of extrinsic information transfer (EXIT) charts is used for analysing both the bit error rate (BER) performance as well as the channel capacity of these systems and the results are verified by Monte Carlo simulations. The proposed Iter-PIC OCDMA system is capable of achieving two orders of magnitude BER improvements and a 0.1 nats of capacity improvement over the conventional chip-level OCDMA systems at a coding rate of 1/10. PMID- 24216822 TI - Imaging cross-correlation FROG: measuring ultrashort, complex, spatiotemporal fields. AB - We present imaging cross-correlation frequency-resolved optical gating (ImXFROG), a new method for the spatiotemporal phase retrieval of ultrashort pulses. It is demonstrated that ImXFROG can measure phase and intensity of arbitrary, spatiotemporally distorted pulses with femtosecond resolution and up to 10(7) independent variables. ImXFROG is implemented as a plug-in upgrade to an existing correlator and used to demonstrate the reconstruction of highly complex, optical pulses with femtosecond features and massive spatiotemporal distortion. PMID- 24216823 TI - Tunable, multiwavelength Tm-doped fiber laser based on polarization rotation and four-wave-mixing effect. AB - We propose and demonstrate a tunable multiwavelength fiber laser employing polarization-maintaining Tm-doped fiber based on polarization rotation and four wave-mixing effect. Polarization-maintaining Tm-doped fiber and polarization controllers were employed to manipulate the polarization modes in the laser, and 400 m long single-mode passive fiber was used to enhance the four-wave-mixing effect and suppress the polarization mode competition. Stable fiber laser operation of 1-6 wavelengths around 1.9 MUm was achieved at room temperatures. The wavelengths can be tuned through adjusting the polarization controllers. The optical signal-to-noise ratio of the laser is more than 31 dB. The wavelength shift is less than 0.05 nm and the peak fluctuation of each wavelength is analyzed. For most of the wavelengths the peak fluctuations are less than 3 dB and the peak fluctuations of wavelengths with more stability are below 1.5 dB. PMID- 24216824 TI - Carrier saturation in multiple quantum well metallo-dielectric semiconductor nanolaser: is bulk material a better choice for gain media? AB - Although multi quantum well (MQW) structure is frequently suggested as the appropriate medium for providing optical gain in nanolasers with low threshold current, we demonstrate that in general bulk gain medium can be a better choice. We show that the high threshold gain required for nanolasers demands high threshold carrier concentrations and therefore a highly degenerate condition in which the barriers between the quantum wells are heavily pumped. As a result, there occurs spontaneous emission from the barrier in very dissipative low Q modes or undesired confined higher Q modes with resonance wavelengths close to the barrier bandgap. This results in a competition between wells and barriers that suppresses lasing. A complete model involving the optical properties of the resonant cavity combined with the carrier injection in the multilayer structure is presented to support our argument. With this theoretical model we show that while lasing is achieved in the nanolaser with bulk gain media, the nanolaser with MQW gain structure exhibits well emission saturation due to the onset of barrier emission. PMID- 24216825 TI - Ring resonator-based on-chip modulation transformer for high-performance phase modulated microwave photonic links. AB - In this paper, we propose and experimentally demonstrate a novel wideband on-chip photonic modulation transformer for phase-modulated microwave photonic links. The proposed device is able to transform phase-modulated optical signals into intensity-modulated versions (or vice versa) with nearly zero conversion of laser phase noise to intensity noise. It is constructed using waveguide-based ring resonators, which features simple architecture, stable operation, and easy reconfigurability. Beyond the stand-alone functionality, the proposed device can also be integrated with other functional building blocks of photonic integrated circuits (PICs) to create on-chip complex microwave photonic signal processors. As an application example, a PIC consisting of two such modulation transformers and a notch filter has been designed and realized in TriPleX(TM) waveguide technology. The realized device uses a 2 * 2 splitting circuit and 3 ring resonators with a free spectral range of 25 GHz, which are all equipped with continuous tuning elements. The device can perform phase-to-intensity modulation transform and carrier suppression simultaneously, which enables high-performance phase-modulated microwave photonics links (PM-MPLs). Associated with the bias free and low-complexity advantages of the phase modulators, a single-fiber-span PM-MPL with a RF bandwidth of 12 GHz (3 dB-suppression band 6 to 18 GHz) has been demonstrated comprising the proposed PIC, where the achieved spurious-free dynamic range performance is comparable to that of Class-AB MPLs using low-biased Mach-Zehnder modulators. PMID- 24216826 TI - Extracavity pumped BaWO4 anti-Stokes Raman laser. AB - The characteristics of a barium tungstate (BaWO(4)) anti-Stokes Raman laser at 968 nm are studied theoretically and experimentally. The BaWO(4) Raman resonator is pumped by a Q-switched Nd:YAG laser at 1064 nm with its axis tilted from the pumping laser axis. The non-collinear phase matching for the generation of the first anti-Stokes wave in the same BaWO(4) crystal is achieved. The output energy, temporal and spectral informations are investigated. At a pumping laser energy of 128 mJ, the anti-Stokes laser energy obtained is 2.2 mJ. The second Stokes radiation at 1324 nm as well as the first and the third Stokes waves at 1180 nm and 1509 nm is also generated at the same time. The maximum total Stokes energy output is 42.5 mJ. In the theory, the anti-Stokes laser intensity expression as a function of the pumping and the first Stokes laser intensities for the extracavity anti-Stokes Raman laser is deduced. The properties of the anti-Stokes Raman laser are simulated theoretically by solving the rate equations of the extracavity Raman laser and using the derived expression. The theoretical results are in good agreement with the experimental results. PMID- 24216827 TI - Stable passively Q-switched and gain-switched Yb-doped all-fiber laser based on a dual-cavity with fiber Bragg gratings. AB - We demonstrate a stable passively Q-switched and gain-switched Yb-doped all-fiber laser cladding-pumped by a continuous fiber-coupled 976 nm laser diode. By use of an all-fiber dual-cavity, the efficient elements of the laser mainly include the fiber Bragg gratings and rare-earth doped fiber, allowing the oscillator to be integrated in a compact size with reliable and stable output. In this scheme, an efficient laser output with 45 ns pulse width, 62 MUJ pulse energy, and 1.4 kW peak power operating at 1081 nm was obtained. To the best of our knowledge, this is the minimum pulse width in this similar kind of all-fiber configuration at present. Sequential nanosecond pulses were obtained at the repetition rate of several to tens of kHz with the variation of the diode pumping power. Effects of laser parameters such as pump power, cavity length, external-cavity wavelength, and FBG reflectivity on laser performance were also presented and discussed. PMID- 24216828 TI - Broadband photoresponse and rectification of novel graphene oxide/n-Si heterojunctions. AB - We report a novel graphene oxide (GO) based p-n heterojunction on n-Si. The fabricated vertical GO/n-Si heterojunction diode shows a very low leakage current density of 0.25 uA/cm(2) and excellent rectification characteristics upto 1 MHz. The device on illumination shows a broadband (300-1100 nm) spectral response with a characteristic peak at ~700 nm, in agreement with the photoluminescence emission from GO. Very high photo-to-dark current ratio (>10(5)) is observed upon illumination of UV light. The transient photocurrent measurements indicate that the GO based heterojunction diodes can be useful for UV and broadband photodetectors, compatible with silicon device technology. PMID- 24216829 TI - Dynamic characterization and amplification of sub-picosecond pulses in fiber optical parametric chirped pulse amplifiers. AB - We show a first-time demonstration of amplification of 400 fs pulses in a fiber optical parametric amplifier. The 400 fs signal is stretched in time, amplified by 26 dB and compressed back to 500 fs. A significant broadening of the pulses is experimentally shown due to dispersion and limited gain bandwidth both in saturated and unsaturated gain regimes. PMID- 24216830 TI - Tunable wavelength dependent nanoswitches enabled by simple plasmonic core-shell particles. AB - In this paper we demonstrate the feasibility of using a plasmonic core-shell particle to function as a wavelength dependent switch for integration into nanoantenna structures. First, a quasistatic analysis is performed and the necessary conditions are derived which allow the particle to operate in either a short- or an open-circuit state. These conditions dictate that the core and the shell permittivity values need to have opposite sign. Consequently, at optical wavelengths where noble metals are modeled as Drude dielectrics, these conditions can be easily realized. As a matter of fact, it is demonstrated that a realistic core-shell particle can exhibit both the short- and open-circuit states, albeit at different wavelengths. Our analysis is extended by examining the same problem beyond the quasistatic limit. For this task we utilize an inhomogeneous spherical transmission line representation of the core-shell particle. The conditions are derived for the particle that yield either an input admittance or impedance equal to zero. It is further demonstrated that these conditions are the short wavelength generalization of their quasistatic counterparts. PMID- 24216831 TI - Analysis of Moire minimization in autostereoscopic parallax displays. AB - In order to minimize moire patterns in autostereoscopic parallax displays, the optical component, which is used for forming viewing zones, is analyzed with varying period and slant angle. First, horizontal-parallax autostereoscopic displays (HPAD) can be approximated as the superposition of three corresponding binary gratings. Referring to the unification of indicial equation method and Fourier analysis, a singular state and two stable moire-free states are obtained according to the superposition of the equivalent grating of LCD and special radial grating. Two stable moire-free states are valid for HPAD. For full parallax autostereoscopic displays (FPAD), a special radial grid grating is introduced to simulate a 2D optical component with progressively varying period and slant angle. Similarly, two corresponding stable moire-free states for FPAD can be used for eliminating moire patterns. PMID- 24216832 TI - Design method of surface contour for a freeform lens with wide linear field-of view. AB - In this paper, a design method of surface contour for a freeform imaging lens with a wide linear field-of-view (FOV) is developed. During the calculation of the data points on the unknown freeform surfaces, the aperture size and different field angles of the system are both considered. Meanwhile, two special constraints are employed to find the appropriate points that can generate a smooth and accurate surface contour. The surfaces obtained can be taken as the starting point for further optimization. An f-theta single lens with a +/- 60 degrees linear FOV has been designed as an example of the proposed method. After optimization with optical design software, the MTF of the lens is close to the diffraction limit and the scanning error is less than 1 MUm. This result proves that good image quality and scanning linearity were achieved. PMID- 24216833 TI - Nanoscale contact line visualization based on Total Internal Reflection Fluorescence Microscopy. AB - We describe a novel measurement method to study the contact line of a droplet at nanoscale level. The method is based on Total Internal Reflection Fluorescence Microscopy (TIRFM), which uses an evanescent excitation field produced by total internal reflection of light. The evanescent field depends on the angle of the incident light and has an exponential intensity decay, characterized by the penetration depth. The penetration depth is determined by imaging a fluorescent particle probe that is traversed using an Atomic Force Microscopy (AFM) setup. The result confirms the exponential behavior of the evanescent field intensity, and the value of the penetration depth also corresponds with the value predicted based on the optical configuration. By using the intensity distribution of a fluorescent dye and the value for the penetration depth of the evanescent wave, it is possible to reconstruct the interface of a partial wetting droplet. The reconstructed interface based on TIRFM is in good agreement with the interface obtained from two reference measurements: non-disturbing AFM-imaging and conventional contact angle measurement. The latter lacks spatial resolution, while the former is limited to particular droplets. This new non-contact measurement does not suffer from these drawbacks, making it a very useful tool to study the fundamental wetting behavior of both stationary and dynamic interfaces. PMID- 24216834 TI - Beating the classical limit: a diffraction-limited spectrograph for an arbitrary input beam. AB - We demonstrate a new approach to classical fiber-fed spectroscopy. Our method is to use a photonic lantern that converts an arbitrary (e.g. incoherent) input beam into N diffraction-limited outputs. For the highest throughput, the number of outputs must be matched to the total number of unpolarized spatial modes on input. This approach has many advantages: (i) after the lantern, the instrument is constructed from 'commercial off the shelf' components; (ii) the instrument is the minimum size and mass configuration at a fixed resolving power and spectral order; (iii) the throughput is better than 60% (slit to detector, including detector QE of ~80%); (iv) the scattered light at the detector can be less than 0.1% (total power). Our first implementation operates over 1545-1555 nm (limited by the detector) with a spectral resolution of 0.055 nm (R~30,000) using a 1 * 7 (1 multi-mode input to 7 single-mode outputs) photonic lantern. This approach is a first step towards a fully integrated, multimode photonic microspectrograph. PMID- 24216835 TI - Investigation of quantum dot passively mode-locked lasers with excited-state transition. AB - Monolithic passively mode-locked quantum dot lasers with excited-state transition were investigated in a broad operating range without ground-state lasing. Optical and electrical characteristics of these mode locked lasers were studied in detail at different levels of injection current and absorber bias. Very different behaviors in the evolution of the hysteresis, the optical spectra and the evolution of repetition frequency were observed between our lasers and conventional quantum dot lasers with ground-state transition. Possible mechanisms behind these observed phenomena were proposed and discussed. A minimum pulse width of 3.3 ps and an externally compressed pulse width of 0.78 ps were obtained. PMID- 24216836 TI - Comparative analysis of oxidation methods of reaction-sintered silicon carbide for optimization of oxidation-assisted polishing. AB - Combination of the oxidation of reaction-sintered silicon carbide (RS-SiC) and the polishing of the oxide is an effective way of machining RS-SiC. In this study, anodic oxidation, thermal oxidation, and plasma oxidation were respectively conducted to obtain oxides on RS-SiC surfaces. By performing scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM-EDX) analysis and scanning white light interferometry (SWLI) measurement, the oxidation behavior of these oxidation methods was compared. Through ceria slurry polishing, the polishing properties of the oxides were evaluated. Analysis of the oxygen element on polished surfaces by SEM-EDX was conducted to evaluate the remaining oxide. By analyzing the three oxidation methods with corresponding polishing process on the basis of schematic diagrams, suitable application conditions for these methods were clarified. Anodic oxidation with simultaneous polishing is suitable for the rapid figuring of RS-SiC with a high material removal rate; polishing of a thermally oxidized surface is suitable for machining RS-SiC mirrors with complex shapes; combination of plasma oxidation and polishing is suitable for the fine finishing of RS-SiC with excellent surface roughness. These oxidation methods are expected to improve the machining of RS-SiC substrates and promote the application of RS-SiC products in the fields of optics, molds, and ceramics. PMID- 24216837 TI - Refractive index sensitivity enhancement of optical fiber cladding mode by depositing nanofilm via ALD technology. AB - The atomic layer deposition (ALD) technology is introduced to enhance the sensitivity of optical fiber cladding mode to surrounding refractive index (SRI) variation. The highly uniform Al2O nanofilm was deposited around the double cladding fiber (DCF) which presents cladding mode resonant feature. With the high refractive index coating, the cladding mode resonant spectrum was tuned. And the sensitivity enhancement for SRI sensor was demonstrated. Through adjusting the deposition cycles, a maximum sensitivity of 723 nm/RIU was demonstrated in the DCF with 2500 deposition cycles at the SRI of 1.34. Based on the analysis of cladding modes reorganization, the cladding modes transition of the coated DCF was investigated theoretically. With the high performance nanofilm coating, the proposed SRI sensor is expected to have wide applications in chemical sensors and biosensors. PMID- 24216838 TI - Dissipative solitons in the coupled dynamics of light and cold atoms. AB - We investigate the coupled dynamics of light and cold atoms in a unidirectional ring cavity, in the regime of low saturation and linear single-atom response. As the dispersive opto-mechanical coupling between light and the motional degrees of freedom of the atoms makes the dynamics nonlinear, we find that localized, nonlinearity-sustained and bistable structures can be encoded in the atomic density by means of appropriate control beams. PMID- 24216839 TI - Resonance enhanced Raman scatter in liquid benzene at vapor-phase absorption peaks. AB - The resonance enhanced Raman spectra in the 1B2u mode of the forbidden benzene electronic transition band, ~230-270 nm, has been investigated. Resonance enhanced Raman scattering in both liquid benzene and liquid toluene exhibit the greatest enhancement when the wavelength of excitation is tuned to the vapor phase absorption peaks; even though the sample volume is in a liquid state. Raman signals for the symmetric breathing mode of the carbon ring are found to be resonantly enhanced by several orders of magnitude (>500X) with deep UV excitation compared to non-resonant visible excitation. Since the benzene absorbs near this resonant wavelength, its effect on the sampled volume cannot be neglected in determining the resonance gain, as we discuss in detail. Large resonant gains correspond with excitation at the 247, 253, and 259 nm absorption peaks in the benzene vapor spectrum. The narrow region of resonance gain is investigated in detail around the absorption peak located at 259 nm using 0.25 nm steps in the excitation wavelength. We observe the resonance gain tracking the vapor phase absorption peaks and valleys within this narrow range. Results are interpreted in terms of the coherence forced by the use of a forbidden transition for resonance excitation. PMID- 24216840 TI - Full-field dual-color 100-nm super-resolution imaging reveals organization and dynamics of mitochondrial and ER networks. AB - Most structured illumination microscopes use a physical or synthetic grating that is projected into the sample plane to generate a periodic illumination pattern. Albeit simple and cost-effective, this arrangement hampers fast or multi-color acquisition, which is a critical requirement for time-lapse imaging of cellular and sub-cellular dynamics. In this study, we designed and implemented an interferometric approach allowing large-field, fast, dual-color imaging at an isotropic 100-nm resolution based on a sub-diffraction fringe pattern generated by the interference of two colliding evanescent waves. Our all-mirror-based system generates illumination pat-terns of arbitrary orientation and period, limited only by the illumination aperture (NA = 1.45), the response time of a fast, piezo-driven tip-tilt mirror (10 ms) and the available fluorescence signal. At low uW laser powers suitable for long-period observation of life cells and with a camera exposure time of 20 ms, our system permits the acquisition of super resolved 50 um by 50 um images at 3.3 Hz. The possibility it offers for rapidly adjusting the pattern between images is particularly advantageous for experiments that require multi-scale and multi-color information. We demonstrate the performance of our instrument by imaging mitochondrial dynamics in cultured cortical astrocytes. As an illustration of dual-color excitation dual-color detection, we also resolve interaction sites between near-membrane mitochondria and the endoplasmic reticulum. Our TIRF-SIM microscope provides a versatile, compact and cost-effective arrangement for super-resolution imaging, allowing the investigation of co-localization and dynamic interactions between organelles- important questions in both cell biology and neurophysiology. PMID- 24216841 TI - Dual-crystal Yb:CALGO high power laser and regenerative amplifier. AB - This paper reports on a high-power dual-crystal Yb:CALGO laser head with greatly reduced sensitivity to thermal lensing in the gain medium. In continuous-wave operation 23 W of power were extracted from 2% doped crystals, and tunablity between 1018 nm and 1060 nm was demonstrated. This is the highest output power reported from a bulk Yb:CALGO laser to date, as well as the demonstration of the broadest tuning range. 4 mJ pulses at 1040 nm were achieved in cavity-dumped operation with quasi-CW pumping at 1 kHz repetition rate with nearly diffraction limited beam quality. When seeded at 1030 nm with stretched femtosecond pulses, 3 mJ were achieved. PMID- 24216842 TI - Excitability in optically injected microdisk lasers with phase controlled excitatory and inhibitory response. AB - We demonstrate class I excitability in optically injected microdisk lasers, and propose a possible optical spiking neuron design. The neuron has a clear threshold and an integrating behavior, leading to an output rate-input rate dependency that is comparable to the characteristic of sigmoidal artificial neurons. We also show that the optical phase of the input pulses has influence on the neuron response, and can be used to create inhibitory, as well as excitatory perturbations. PMID- 24216843 TI - Real-time white-light phosphor-LED visible light communication (VLC) with compact size. AB - In this demonstration, we first demonstrate a real-time phosphor-LED visible light communication (VLC) system with 37 Mbit/s total throughput under a 1.5 m free space transmission length. The transmitter and receiver modules are compact size. Utilizing our proposed pre-equalization technology, the ~1 MHz bandwidth of phosphor LED could be extended to ~12 MHz without using blue filter. Thus, the increase in bandwidth would enhance the traffic data rate for VLC transmission. The maximum bit-rate achieved by the VLC system is 37 Mbit/s, and a video transmission at 28.419 Mbit/s is demonstrated using the proposed VLC system. In addition, the relationships of received power and signal performance are discussed and analyzed. PMID- 24216844 TI - Vibration frequency measurement using a local multithreshold technique. AB - In this paper, we demonstrate the use of a video camera for measuring the frequency of small-amplitude vibration movements. The method is based on image acquisition and multilevel thresholding and it only requires a video camera with high enough acquisition rate, not being necessary the use of targets or auxiliary laser beams. Our proposal is accurate and robust. We demonstrate the technique with a pocket camera recording low-resolution videos with AVI-JPEG compression and measuring different objects that vibrate in parallel or perpendicular direction to the optical sensor. Despite the low resolution and the noise, we are able to measure the main vibration modes of a tuning fork, a loudspeaker and a bridge. Results are successfully compared with design parameters and measurements with alternative devices. PMID- 24216845 TI - Dynamic TWDM-PON for mobile radio access networks. AB - In recent years, the diffusion of mobile terminals has brought about an explosive increase in communication traffic of mobile RANs. The number of radio base stations and optical fiber lines between them is becoming larger. For this reason, we studied effective optical network technologies for mobile RANs and propose the use of TWDM-PON as a means of enabling RANs to be operated flexibly and have wideband communication capability. We confirmed the feasibility of TWDM PON for this application by numerical simulation. The results show that TWDM-PON can accommodate the bandwidth more than TDM-PON and completely eliminate unused bandwidth in TDM-PON. PMID- 24216846 TI - Three-dimensional deep sub-wavelength defect detection using lambda = 193 nm optical microscopy. AB - Optical microscopy is sensitive both to arrays of nanoscale features and to their imperfections. Optimizing scattered electromagnetic field intensities from deep sub-wavelength nanometer scale structures represents an important element of optical metrology. Current, well-established optical methods used to identify defects in semiconductor patterning are in jeopardy by upcoming sub-20 nm device dimensions. A novel volumetric analysis for processing focus-resolved images of defects is presented using simulated and experimental examples. This new method allows defects as narrow as (16 +/- 2) nm (k = 1) to be revealed using 193 nm light with focus and illumination conditions optimized for three-dimensional data analysis. Quantitative metrics to compare two-dimensional and three-dimensional imaging indicate possible fourfold improvements in sensitivity using these methods. PMID- 24216847 TI - Digitally tunable holographic lithography using a spatial light modulator as a programmable phase mask. AB - In this paper, we study tunable holographic lithography using an electrically addressable spatial light modulator as a programmable phase mask. We control the phases of interfering beams diffracted from the phase pattern displayed in the spatial light modulator. We present a calculation method for the assignment of phases in the laser beams and validate the phases of the interfering beams in phase-sensitive, dual-lattice, and two-dimensional patterns formed by a rotationally non-symmetrical configuration. A good agreement has been observed between fabricated holographic structures and simulated interference patterns. The presented method can potentially help design a gradient phase mask for the fabrication of graded photonic crystals or metamaterials. PMID- 24216848 TI - Enhanced luminescence efficiency of Ag nanoparticles dispersed on indium tin oxide for polymer light-emitting diodes. AB - This study presents a substantial enhancement in electroluminescence achieved by depositing Ag nanoparticles on an ITO-coated glass substrate (Ag/ITO) for approximately 10-s to form novel window materials for use in polymer light emitting diodes (PLEDs). The PLEDs discussed herein are single-layer devices based on a poly[9,9-dioctylfluorene-co-benzothiadiazole] (F8BT) emissive layer. In addition to its low cost, this novel fabrication method can effectively increase the charge transport properties of the active layer to meet the high performance requirements of PLEDs. Due to the increased conductivity and work function of the Ag/ITO substrate, the electroluminescence intensity was increased by nearly 3.3-fold compared with that of the same PLED with a bare ITO substrate. PMID- 24216849 TI - Three-dimensional multi-photon direct laser writing with variable repetition rate. AB - We perform multi-photon direct laser writing as a function of laser repetition rate over many orders of magnitude and otherwise unchanged experimental conditions. These new data serve as basis for investigating the influence of different proposed mechanisms involved in the photopolymerization: two-photon absorption, photoionization, avalanche ionization and heat accumulation. We find different non-linearities for high and low repetition rates consistent with different initiation processes being involved. The scaling of the resulting linewidths, however, is neither expected nor found to depend on repetition rate or non-linearity. PMID- 24216850 TI - High-power tunable single- and multi-wavelength diode-pumped Nd:YAP laser in the (4)F3/2 -> (4)I11/2 transition. AB - We experimentally explore the fluorescent spectrum of the Nd:YAP crystal to manifest the feasibility of tunable single- and multi-wavelength operations in the (4)F3/2 -> (4)I11/2 transition. An intracavity etalon is subsequently exploited to effectively select spectral lines at 1073, 1080, and 1084 nm with the tunabilities of 0.56, 1.13, and 0.1 nm, respectively. We also experimentally obtain multi-wavelength oscillations among various intermanifold lines in the Nd:YAP crystal with the output powers on the order of several watts for each group. Employing the Cr(4+):YAG crystal to realize the passively Q-switched operation, the maximum average output powers as high as 2.3 and 3.5 W for 1073 and 1080 nm are obtained. The corresponding pulse energies at 1073 and 1080 nm are up to 177 and 159 MUJ, respectively. PMID- 24216851 TI - Wide color gamut LCD with a quantum dot backlight. AB - We analyze the color performance and system efficiency of three commonly employed liquid crystal display modes with a blue LED-pumped red and green quantum dots (QDs) backlight. Based on the measured QD emission spectra, we can achieve 115% color gamut in CIE 1931 and 140% in CIE 1976 color space, while keeping the same energy efficiency as conventional backlights. Next, we apply multi-objective optimization method to refine the QD emission spectra and find a fundamental tradeoff between display system efficiency and color gamut. This systematic photometric analysis also provides useful guidelines for further optimizing QD backlight design and display system efficiency. PMID- 24216852 TI - Designing dielectric resonators on substrates: combining magnetic and electric resonances. AB - High-performance integrated optics, solar cells, and sensors require nanoscale optical components at the surface of the device, in order to manipulate, redirect and concentrate light. High-index dielectric resonators provide the possibility to do this efficiently with low absorption losses. The resonances supported by dielectric resonators are both magnetic and electric in nature. Combined scattering from these two can be used for directional scattering. Most applications require strong coupling between the particles and the substrate in order to enhance the absorption in the substrate. However, the coupling with the substrate strongly influences the resonant behavior of the particles. Here, we systematically study the influence of particle geometry and dielectric environment on the resonant behavior of dielectric resonators in the visible to near-IR spectral range. We show the key role of retardation in the excitation of the magnetic dipole (MD) mode, as well as the limit where no MD mode is supported. Furthermore, we study the influence of particle diameter, shape and substrate index on the spectral position, width and overlap of the electric dipole (ED) and MD modes. Also, we show that the ED and MD mode can selectively be enhanced or suppressed using multi-layer substrates. And, by comparing dipole excitation and plane wave excitation, we study the influence of driving field on the scattering properties. Finally, we show that the directional radiation profiles of the ED and MD modes in resonators on a substrate are similar to those of point-dipoles close to a substrate. Altogether, this work is a guideline how to tune magnetic and electric resonances for specific applications. PMID- 24216853 TI - Development and calibration of a single UV LED based bioaerosol monitor. AB - A high-sensitivity bioaerosol monitor based on a single 365 nm LED is developed and a calibration approach is discussed for the first time. The fluorescence detection system, which is the core part of the monitor, contains an optical detection module and a fluorescence signal processor configured with a phase sensitive detector (PSD). B800 fluorescent microspheres and staphylococcus are used for performance evaluation of the monitor. B800 microspheres are appropriate as calibration material. The experimental results demonstrate the PSD plays a significant role in improving sensitivity and signal-to-noise ratio (SNR) of detection. Our monitor can detect staphylococcus concentration above 1800 cfu/L of air stably. PMID- 24216854 TI - Realizing vertical light coupling and splitting in nano-plasmonic multilevel circuits. AB - We present a novel technique for vertical coupling of light guided by nanoscale plasmonic slot waveguides (PSWs). A triangularly-shaped plasmonic slot waveguide rotator is exploited to attain such coupling with a good efficiency over a wide bandwidth. Using this approach, light propagating in a horizontal direction is efficiently coupled to propagate in the vertical direction and vice versa. We also propose a power divider configuration to evenly split a vertically coupled light wave to two horizontal channels. A detailed parametric study of the triangular rotator is demonstrated with multiple configurations analyzed. This structure is suitable for efficient coupling in multilevel nano circuit environment. PMID- 24216855 TI - Growth of high spatial frequency periodic ripple structures on SiC crystal surfaces irradiated with successive femtosecond laser pulses. AB - We present experimentally and theoretically the evolution of high spatial frequency periodic ripples (HSFL) fabricated on SiC crystal surfaces by irradiation with femtosecond laser pulses in a vacuum chamber. At early stages the seed defects are mainly induced by laser pulse irradiation, leading to the reduction in the ablation threshold fluence. By observing the evolution of these surface structures under illumination with successive laser pulses, the nanocraters are made by nanoablation at defects in the SiC surface. The Mie scattering by the nanoablated craters grows the periodic ripples. The number of HSFL is enhanced with increasing pulse number. At the edge of the laser spot the Mie scattering process is still dominant, causing the fabrication of HSFL. On the periphery of the spot SiC substrate remains a semiconductor state because the electron density in the SiC induced by laser irradiation is kept low. The HSFL observed is very deep in the SiC surface by irradiating with many laser pulses. These experimental results are well explained by 3D FDTD (three-dimensional finite-difference time-domain) simulation. PMID- 24216856 TI - Optical vault: a reconfigurable bottle beam based on conical refraction of light. AB - We employ conical refraction of light in a biaxial crystal to create an optical bottle for photophoretic trapping and manipulation of particles in gaseous media. We show that by only varying the polarization state of the input light beam the optical bottle can be opened and closed in order to load and unload particles in a highly controllable manner. PMID- 24216857 TI - Femtosecond laser damage threshold of pulse compression gratings for petawatt scale laser systems. AB - Laser-induced femtosecond damage thresholds of Au and Ag coated pulse compression gratings were measured using 800 nm laser pulses ranging in duration from 30 to 200 fs. These gratings differ from conventional metal-on-photoresist pulse compression gratings in that the gratings patterns are generated by etching the fused silica substrate directly. After etching, the metal overcoating was optimized based on diffraction efficiency and damage threshold considerations. The experiment on these gratings was performed under vacuum for single-shot damage. Single-shot damage threshold, where there is a 0% probability of damage, was determined to be within a 400-800 mJ/cm(2) range. The damage threshold exhibited no clear dependence on pulse width, but showed clear dependence on gold overcoat surface morphology. This was confirmed by electromagnetic field modeling using the finite element method, which showed that non-conformal coating morphology gives rise to significant local field enhancement near groove edges, lowering the diffraction efficiency and increasing Joule heating. Large-scale gratings with conformal coating have been installed successfully in the 500 TW Scarlet laser system. PMID- 24216858 TI - The coherent gradient sensor for film curvature measurements at cryogenic temperature. AB - Coherent Gradient Sensor (CGS) system is presented for measurement of curvatures and nonuniform curvatures changes in film-substrate systems at cryogenic temperature. The influences of the interface of refrigerator and itself on the interferograms which are accounting for the temperature effect are successfully eliminated. Based on the measurement technique, the thermal stresses (including the radial stress, circumferential stress and shear stress) of superconducting YBCO thin-film are obtained by the extended Stoney's formula during the heating process from 30K to 150K. Take the superconducting YBCO thin film as an example, the thermal stresses of which are gained successfully. PMID- 24216859 TI - Fluence scan: an unexplored property of a laser beam. AB - We present an extended theoretical background of so-called fluence scan (f-scan or F-scan) method, which is frequently being used for offline characterization of focused short-wavelength (EUV, soft X-ray, and hard X-ray) laser beams [J. Chalupsky et al., Opt. Express 18, 27836 (2010)]. The method exploits ablative imprints in various solids to visualize iso-fluence beam contours at different fluence and/or clip levels. An f-scan curve (clip level as a function of the corresponding iso-fluence contour area) can be generated for a general non Gaussian beam. As shown in this paper, fluence scan encompasses important information about energy distribution within the beam profile, which may play an essential role in laser-matter interaction research employing intense non-ideal beams. Here we for the first time discuss fundamental properties of the f-scan function and its inverse counterpart (if-scan). Furthermore, we extensively elucidate how it is related to the effective beam area, energy distribution, and to the so called Liu's dependence [J. M. Liu, Opt. Lett. 7, 196 (1982)]. A new method of the effective area evaluation based on weighted inverse f-scan fit is introduced and applied to real data obtained at the SCSS (SPring-8 Compact SASE Source) facility. PMID- 24216860 TI - On nonlinearly-induced noise in single-channel optical links with digital backpropagation. AB - In this paper, we investigate the performance limits of electronic chromatic dispersion compensation (EDC) and digital backpropagation (DBP) for a single channel non-dispersion-managed fiber-optical link. A known analytical method to derive the performance of the system with EDC is extended to derive a first-order approximation for the performance of the system with DBP. In contrast to the cubic growth of the variance of the nonlinear noise-like interference, often called nonlinear noise, with input power for EDC, a quadratic growth is observed with DBP using this approximation. Finally, we provide numerical results to verify the accuracy of the proposed approach and compare it with existing analytical models. PMID- 24216861 TI - Electro-optical modulation of a silicon waveguide with an "epsilon-near-zero" material. AB - Accumulating electrons in transparent conductive oxides such as indium tin oxide (ITO) can induce an "epsilon-near-zero" (ENZ) in the spectral region near the important telecommunications wavelength of lambda = 1.55 MUm. Here we theoretically demonstrate highly effective optical electro-absorptive modulation in a silicon waveguide overcoated with ITO. This modulator leverages the combination of a local electric field enhancement and increased absorption in the ITO when this material is locally brought into an ENZ state via electrical gating. This leads to large changes in modal absorption upon gating. We find that a 3 dB modulation depth can be achieved in a non-resonant structure with a length under 30 MUm for the fundamental waveguide modes of either linear polarization, with absorption contrast values as high as 37. We also show a potential for 100 fJ/bit modulation, with a sacrifice in performance. PMID- 24216862 TI - Synthetic phase-shifting for optical testing: point-diffraction interferometry without null optics or phase shifters. AB - An innovative iterative search method called the synthetic phase-shifting (SPS) algorithm is proposed. This search algorithm is used for maximum-likelihood (ML) estimation of a wavefront that is described by a finite set of Zernike Fringe polynomials. In this paper, we estimate the coefficient, or parameter, values of the wavefront using a single interferogram obtained from a point-diffraction interferometer (PDI). In order to find the estimates, we first calculate the squared-difference between the measured and simulated interferograms. Under certain assumptions, this squared-difference image can be treated as an interferogram showing the phase difference between the true wavefront deviation and simulated wavefront deviation. The wavefront deviation is the difference between the reference and the test wavefronts. We calculate the phase difference using a traditional phase-shifting technique without physical phase-shifters. We present a detailed forward model for the PDI interferogram, including the effect of the finite size of a detector pixel. The algorithm was validated with computational studies and its performance and constraints are discussed. A prototype PDI was built and the algorithm was also experimentally validated. A large wavefront deviation was successfully estimated without using null optics or physical phase-shifters. The experimental result shows that the proposed algorithm has great potential to provide an accurate tool for non-null testing. PMID- 24216863 TI - Numerical study of the properties of optical vortex array laser tweezers. AB - Chu et al. constructed a kind of Ince-Gaussian modes (IGM)-based vortex array laser beams consisting of p x p embedded optical vortexes from Ince-Gaussian modes, IG(e)(p,p) modes [Opt. Express 16, 19934 (2008)]. Such an IGM-based vortex array laser beams maintains its vortex array profile during both propagation and focusing, and is applicable to optical tweezers. This study uses the discrete dipole approximation (DDA) method to study the properties of the IGM-based vortex array laser tweezers while it traps dielectric particles. This study calculates the resultant force exerted on the spherical dielectric particles of different sizes situated at the IGM-based vortex array laser beam waist. Numerical results show that the number of trapping spots of a structure light (i.e. IGM-based vortex laser beam), is depended on the relation between the trapped particle size and the structure light beam size. While the trapped particle is small comparing to the beam size of the IGM-based vortex array laser beams, the IGM-based vortex array laser beams tweezers are suitable for multiple traps. Conversely, the tweezers is suitable for single traps. The results of this study is useful to the future development of the vortex array laser tweezers applications. PMID- 24216864 TI - Uncertainty characterization of particle depth measurement using digital in-line holography and the hybrid method. AB - In the detection of particles using digital in-line holography, measurement accuracy is substantially influenced by the hologram processing method. In particular, a number of methods have been proposed to determine the out-of-plane particle depth (z location). However, due to the lack of consistent uncertainty characterization, it has been unclear which method is best suited to a given measurement problem. In this work, depth determination accuracies of seven particle detection methods, including a recently proposed hybrid method, are systematically investigated in terms of relative depth measurement errors and uncertainties. Both synthetic and experimental holograms of particle fields are considered at conditions relevant to particle sizing and tracking. While all methods display a range of particle conditions where they are most accurate, in general the hybrid method is shown to be the most robust with depth uncertainty less than twice the particle diameter over a wide range of particle field conditions. PMID- 24216865 TI - Diode-pumped wideband thulium-doped fiber amplifiers for optical communications in the 1800 - 2050 nm window. AB - We present the first in-band diode-pumped TDFAs operating in the 2 um wavelength region and test their suitability as high performance amplifiers in potential future telecommunication networks. We demonstrate amplification over a 240 nm wide window in the range 1810 - 2050 nm with up to 36 dB gain and noise figure as low as 4.5 dB. PMID- 24216866 TI - Method for chromatic error compensation in digital color holographic imaging. AB - This paper proposes an all-numerical robust method to compensate for the chromatic aberrations induced by the optical elements in digital color holographic imaging. It combines a zero-padding algorithm and a convolution approach with adjustable magnification, using a single recording of a reference rectangular grid. Experimental results confirm and validate the proposed approach. PMID- 24216867 TI - Pulsed laser deposition of hexagonal GaN-on-Si(100) template for MOCVD applications. AB - Growth of hexagonal GaN on Si(100) templates via pulsed laser deposition (PLD) was investigated for the further development of GaN-on-Si technology. The evolution of the GaN growth mechanism at various growth times was monitored by SEM and TEM, which indicated that the GaN growth mode changes gradually from island growth to layer growth as the growth time increases up to 2 hours. Moreover, the high-temperature operation (1000 degrees C) of the PLD meant no significant GaN meltback occurred on the GaN template surface. The completed GaN templates were subjected to MOCVD treatment to regrow a GaN layer. The results of X-ray diffraction analysis and photoluminescence measurements show not only the reliability of the GaN template, but also the promise of the PLD technique for the development of GaN-on-Si technology. PMID- 24216868 TI - Temperature dependence of Raman scattering in bulk 4H-SiC with different carrier concentration. AB - Raman spectra of three bulk 4H-SiC wafers with different free carrier concentration were measured at temperature from 80 K to 873 K. As temperature increases, Raman peaks of most optical phonon modes show monotonous down shift. An anomalous non-monotonous variation with temperature, was observed in the A(1) longitudinal optical (LO) mode from doped samples. Two methods of theoretical fitting, one-mode (LO-plasma coupled (LOPC) mode) and two-mode (A(1)(LO) + LOPC) fitting, are employed to analyze this anomalous phenomenon. Theoretical simulations for temperature dependent Raman spectra by using two methods are critically examined. It turns out that one-mode method conforms well the experimental results, while two-mode method is untenable in physics. The non monotonous variation of blue-red shifts with temperature for LOPC mode from doped 4H-SiC could be explained by the influence from ionization process of impurities on the process of Raman scattering. A quantitative description on temperature dependent Raman spectra for doped 4H-SiC is achieved, which matches well to experimental data. PMID- 24216869 TI - Molecular fluorescence in the vicinity of a charged metallic nanoparticle. AB - The modified fluorescence properties of a molecule in the vicinity of a metallic nanoparticle are further studied accounting for the possible existence of extraneous charges on the particle surface. This is achieved via a generalization of the previous theory of Bohren and Hunt for light scattering from a charged sphere, with the results applied to the calculation of the various decay rates and fluorescence yield of the admolecule. Numerical results show that while charge effects will in general blue-shift all the plasmonic resonances of the metal particle, both the quantum yield and the fluorescence yield can be increased at emission frequencies close to that of the surface plasmon resonance of the particle due to the suppression of the nonradiative decay rate. This provides a possibility of further enhancing the particle-induced molecular fluorescence via the addition of surface charge to the metal particle. PMID- 24216870 TI - Degeneration of Fraunhofer diffraction on bacterial colonies due to their light focusing properties examined in the digital holographic microscope system. AB - The degeneration of Fraunhofer diffraction conditions in the optical system with converging spherical wave illumination for bacteria species identification based on diffraction patterns is analyzed by digital holographic methods. The obtained results have shown that the colonies of analyzed bacteria species act as biological lenses with the time-dependent light focusing properties, which are characterized and monitored by means of phase retrieval from sequentially captured digital holograms. This significantly affects the location of Fraunhofer patterns observation plane, which is continuously shifted across optical axis in time. PMID- 24216871 TI - Cr:ZnS saturable absorber passively Q-switched Tm,Ho:GdVO4 laser. AB - A passively Q-switched Tm,Ho:GdVO4 laser operating at cryogenic temperature with a Cr(2+):ZnS saturable absorber pumped with continuous wave LDs was demonstrated. The performance of the laser was investigated through changing the distance between Cr(2+):ZnS and output coupler. The maximum pulse energy of 70.5 MUJ was obtained at 10 W input power. The maximum average output power of PQS laser was up to 3.2 W at the pump power of 22.8 W, corresponding to CW output power of 7.4 W, pulse repetition frequency of 52 kHz, and a pulse width of 389 ns. The M(2) factor measured by the traveling knife-edge method was ~1.1 in x and y directions with near-diffraction limited beam quality. PMID- 24216872 TI - Direct-detection optical OFDM superchannel for long-reach PON using pilot regeneration. AB - We demonstrate a novel long-reach PON downstream scheme based on the regenerated pilot assisted direct-detection optical orthogonal frequency division multiplexing (DDO-OFDM) superchannel transmission. We use the optical comb source to form DDO-OFDM superchannel, and reserve the center carrier as a seed pilot. The seed pilot is further tracked and reused to generate multiple optical carriers at the local exchange. Each regenerated pilot carrier is selected to beat with an adjacent OFDM sub-band at ONU, so that the electrical bandwidth limitation can be much released compared to the conventional DDO-OFDM superchannel detection. With the proposed proof-of-concept architecture, we experimentally demonstrated a 116.7 Gb/s superchannel OFDM-PON system with transmission reach of 100 km, and 1:64 splitting ratio. We analyze the impact of carrier-to-sideband power ratio (CSPR) on system performance. The experiment result shows that, 5 dB power margin is still remained at ONU using such technique. PMID- 24216873 TI - Liquid-crystal micro-lens array with two-divided and tetragonally hole-patterned electrodes. AB - We propose a liquid crystal (LC) micro-lens array with the structure of two divided and tetragonally hole-patterned electrodes. Each LC cell in the lens array behaves like cylindrical or spherical lens properties by electrically adjusting the applied voltages. The LC micro-lens array is useful for tuning optical properties such a focal length and deflection angle of a light emitting diode (LED) illumination system. PMID- 24216874 TI - Adaptive nonlinear Volterra equalizer for mitigation of chirp-induced distortions in cost effective IMDD OFDM systems. AB - We report experimental validations of an adaptive 2nd order Volterra equalization scheme for cost effective IMDD OFDM systems. This equalization scheme was applied to both uplink and downlink transmission. Downlink settings were optimized for maximum bitrate where we achieved 34 Gb/s over 10 km of SSMF using an EML with 10 GHz bandwidth. For the uplink, maximum reach was optimized achieving 14 Gb/s using a low-cost DML with 2.5 GHz bandwidth. PMID- 24216875 TI - Sub-femtosecond timing jitter, all-fiber, CNT-mode-locked Er-laser at telecom wavelength. AB - We demonstrate a 490-attosecond timing jitter (integration bandwidth: 10 kHz - 39.4 MHz) optical pulse train from a 78.7-MHz repetition rate, all-fiber soliton Er laser mode-locked by a fiber tapered carbon nanotube saturable absorber (ft CNT-SA). To achieve this jitter performance, we searched for a net cavity dispersion condition where the Gordon-Haus jitter is minimized while maintaining stable soliton mode-locking. Our result shows that optical pulse trains with well below a femtosecond timing jitter can be generated from a self-starting and robust all-fiber laser operating at telecom wavelength. PMID- 24216876 TI - Interleaved optical coherence tomography. AB - We present a novel and cost-effective technique--interleaved optical coherence tomography (iOCT)--to enhance the imaging speed of swept source OCT systems by acquiring data from multiple lateral positions simultaneously during a single wavelength sweep, using a single detector and a virtually imaged phase array (VIPA) as a multi-band demultiplexer. This technique uses spectral encoding to convert coherence length into higher imaging speed; the speed enhancement factor is independent of the source speed or center wavelength, and the effective A-scan rate scales linearly with sweep speed. The optical configuration requires only a change in the sample arm of a traditional OCT system and preserves the axial resolution and fall-off characteristic of a traditional SS-OCT using the same light source. Using 10 kHz, 20 kHz and 100 kHz sources we provide a first demonstration of image speed enhancement factors of up to 12, 6 and 10, respectively, which yield effective A-scan rates of 120 kHz, 120 kHz and 1 MHz for B-scan imaging, with a sensitivity of up to 82.5 dB. We also show that iOCT can image faster dynamics than traditional OCT B-scan imaging and is capable of 3D biological imaging. The iOCT concept suggests a new route to high-speed OCT imaging for laser developers: that is, by focusing on improving the coherence length and linewidth of existing and emerging sources. Hence, iOCT is a nice complement to ongoing research and commercial efforts to enable faster imaging through development of lasers with faster sweep rates, and offers new hope for existing sources with slow sweep rates and potential for enhancement of coherence length to compete with faster sources to achieve high-speed OCT. PMID- 24216877 TI - Athermal silicon microring resonators with titanium oxide cladding. AB - We describe a novel approach for CMOS-compatible passively temperature insensitive silicon based optical devices using titanium oxide cladding which has a negative thermo-optic (TO) effect. We engineer the mode confinement in Si and TiO2 such that positive TO of Si is exactly cancelled out by negative TO of TiO2. We demonstrate robust operation of the resulting device over 35 degrees. PMID- 24216878 TI - Wave front adaptation using a deformable mirror for adiabatic nanofocusing along an ultrasharp gold taper. AB - We describe and demonstrate the use of an adaptive wave front optimization scheme for enhancing the efficiency of adiabatic nanofocusing of surface plasmon polariton (SPP) waves along an ultrasharp conical gold taper. Adiabatic nanofocusing is an emerging and promising scheme for controlled focusing of far field light into nanometric volumes. It comprises three essential steps: SPP excitation by coupling far field light to an SPP waveguide, SPP propagation along the waveguide and adiabatic SPP nanofocusing towards a geometric singularity. For commonly used complex waveguide geometries, such as, e.g., conical metal tapers, a realistic modeling and efficiency optimization is challenging. Here, we use a deformable mirror to adaptively control the wave front of the incident far field light. We demonstrate an eight-fold enhancement in nanofocusing efficiency and analyze the shape of the resulting optimized wave front. The introduced wave front optimization scheme is of general interest for guiding and controlling light on the nanoscale. PMID- 24216879 TI - Closed-loop resonant fiber optic gyro with an improved digital serrodyne modulation. AB - To widen the linear dynamic range and improve the linearity, a closed-loop resonant fiber optic gyro (RFOG) is proposed and experimentally demonstrated. To overcome the effect of the imperfect serrodyne modulation, an improved frequency shifting module is designed and constructed on a LiNbO3 phase modulator. Its frequency resolution is improved to 0.01 Hz which is equivalent to a rotation rate of 0.04 degrees /h for an RFOG with a 12-cm diameter fiber ring resonator. With the frequency shifter applied in the RFOG, a closed-loop detection is demonstrated, whose bias stability is around 2 degrees /h, close to that of the open-loop output. Moreover, good linearity and wide dynamic range are also experimentally demonstrated thanks to the closed-loop operation. The measured result shows that the open-loop linear detection range of +/- 215 degrees /s is improved to +/- 1076 degrees /s. It is improved by a factor of 5. The open-loop scale factor nonlinearity of 1.2% is decreased to 0.02% (200 ppm), which is improved by a factor of 60. These are the best results reported to date, to the best of our knowledge, for closed-loop RFOGs. PMID- 24216880 TI - Joint sparsity-driven non-iterative simultaneous reconstruction of absorption and scattering in diffuse optical tomography. AB - Some optical properties of a highly scattering medium, such as tissue, can be reconstructed non-invasively by diffuse optical tomography (DOT). Since the inverse problem of DOT is severely ill-posed and nonlinear, iterative methods that update Green's function have been widely used to recover accurate optical parameters. However, recent research has shown that the joint sparse recovery principle can provide an important clue in achieving reconstructions without an iterative update of Green's function. One of the main limitations of the previous work is that it can only be applied to absorption parameter reconstruction. In this paper, we extended this theory to estimate the absorption and scattering parameters simultaneously when the background optical properties are known. The main idea for such an extension is that a joint sparse recovery step gives us unknown fluence on the estimated support set, which eliminates the nonlinearity in an integral equation for the simultaneous estimation of the optical parameters. Our numerical results show that the proposed algorithm reduces the cross-talk artifacts between the parameters and provides improved reconstruction results compared to existing methods. PMID- 24216881 TI - Generation of 2.6-mJ 400-kW pulses from a compact Yb:Gd3Ga5O12 laser repetitively Q-switched by an acousto-optic modulator. AB - An efficient, acousto-optically Q-switched, and compact Yb:Gd(3)Ga(5)O(12) laser oscillating around 1026 nm is demonstrated, producing an output power of 5.15 W at a pulse repetition rate of 2 kHz, with optical-to-optical and slope efficiencies being 35.8% and 52%, respectively. The generated laser pulses are 6.4 ns in duration (FWHM), with pulse energy and peak power amounting, respectively, to 2.58 mJ and 403 kW. PMID- 24216882 TI - Broadly tunable femtosecond mid-infrared source based on dual photonic crystal fibers. AB - We report a novel scheme of generating broadly tunable femtosecond mid-IR pulses based on difference frequency mixing the outputs from dual photonic crystal fibers (PCF). With a 1.3 W, 1035 nm, 300 fs and 40 MHz Yb fiber chirped pulse amplifier as the laser source, a PCF with single zero dispersion wavelength (ZDW) at the laser wavelength is employed to spectrally broaden a portion of the laser pulses. Facilitated by self-phase modulation, its output spectrum possesses two dominant outermost peaks that can be extended to 970 nm and 1092 nm. A different PCF with two closely spaced ZDWs around the laser wavelength is used to generate the intense Stokes pulses between 1240 - 1260 nm. Frequency mixing the dual PCFs outputs in an AgGaS(2) crystal results in mid-IR pulses broadly tunable from 4.2 MUm to 9 MUm with a maximum average power of 640 uW at 4.5 MUm, corresponding to 16 pJ of pulse energy. PMID- 24216883 TI - Arbitrary birefringent metamaterials for holographic optics at lambda = 1.55 MUm. AB - This paper presents an optical element capable of multiplexing two diffraction patterns for two orthogonal linear polarizations, based on the use of non resonant metamaterial cross elements. The metamaterial cross elements provide unique building blocks for engineering arbitrary birefringence. As a proof-of concept demonstration, we present the design and experimental characterization of a polarization multiplexed blazed diffraction grating and a polarization multiplexed computer-generated hologram, for the telecommunication wavelength of lambda = 1.55 MUm. A quantitative study of the polarization multiplexed grating reveals that this approach yields a very large polarization contrast ratio. The results show that metamaterials can form the basis for a versatile and compact platform useful in the design of multi-functional photonic devices. PMID- 24216884 TI - Spatiotemporal control of femtosecond plasmon using plasmon response functions measured by near-field scanning optical microscopy (NSOM). AB - Spectral interferometry combined with near-field scanning optical microscopy is applied in the spatiotemporal characterization of femtosecond plasmon localized at gold nanostructures and surface plasmon polariton in an air-gap waveguide. Based on the plasmon response function in both the amplitude and the phase obtained from the measurements, we deterministically tailored the femtosecond plasmon pulse by shaping the femtosecond excitation laser pulses. PMID- 24216885 TI - Color rendition engineering of phosphor-converted light-emitting diodes. AB - We present an approach to the optimization of the trichromatic spectral power distributions (SPDs) of phosphor-converted (p-c) light-emitting diodes (LEDs) in respect of each of four different color rendition properties (high color fidelity, color saturating, color dulling, and color preference). The approach is based on selecting a model family of Eu2+ phosphors and finding the optimal peak wavelengths of the phosphor bands as functions of the luminous efficacy of radiation. A blue component due to either phosphor photoluminescence or InGaN electroluminescence with the peak wavelength at about 460 nm was found to be an optimal one for the high-fidelity, color-dulling, and color-preference LEDs. The high-fidelity and color-preference LEDs need red phosphors with the peak wavelength of 610-615 nm. The high-fidelity LEDs were shown to require a true green (~530 nm) phosphor component, whereas a cyan (~510 nm) component is the prerequisite of the color-saturating and color-preference LEDs. Deep-blue (~445 nm) and deep-red (~625 nm) components are required for the color-saturating LEDs. A broad yellow band similar to that of Ce(3+) emission is to be used in the color-dulling LEDs. The SPDs of practical phosphor blends for the high-fidelity, color-saturating, and color-preference p-c LEDs are demonstrated. PMID- 24216886 TI - Polycentric spatial focus of time-reversal electromagnetic field in rectangular conductor cavity. AB - Polycentric focus effect of time-reversal (TR) electromagnetic field is found in a rectangular resonant cavity. Theoretical deduction shows that the effect is due to the mirror symmetry of the cavity and the maximum number of focus points is 27 including 1 main focus point and 26 secondary focus points. A case of 6 focus points is calculated, in which the numerical results are consistent with the theoretical predictions, and particularly the 5 secondary focus points have directly resulted in inaccurate imaging and pulse signal interception. PMID- 24216887 TI - Bending performance of large mode area multi-trench fibers. AB - Bending performance of the Multi-trench Fibers (MTFs) has been investigated using the Finite Element Method. Numerical investigations show that MTFs can provide low-loss effective single mode operation under bent configuration, thanks to the resonant coupling of the Higher order Modes (HOMs). Large ratio between the HOMs and the Fundamental Mode (FM) losses can be ensured, although the ratio drops with increasing Effective Area (A(eff)) of the FM. MTFs provide better losses ratio between the HOMs and the FM in comparison with other fibers like step index, W-type, and parabolic fibers. PMID- 24216888 TI - High contrast three-dimensional photoacoustic imaging through scattering media by localized optical fluence enhancement. AB - We demonstrate enhanced three-dimensional photoacoustic imaging behind a scattering material by increasing the fluence in the ultrasound transducer focus. We enhance the optical intensity using wavefront shaping before the scatterer. The photoacoustic signal induced by an object placed behind the scattering medium serves as feedback to optimize the wavefront, enabling one order of magnitude enhancement of the photoacoustic amplitude. Using the enhanced optical intensity, we scan the object in two-dimensions before post-processing of the data to reconstruct the image. The temporal profile of the photoacoustic signal provides the information used to reconstruct the third dimension. PMID- 24216889 TI - Near-field effect in the infrared range through periodic Germanium subwavelength arrays. AB - Using finite-difference-time-domain simulation, we have studied the near-field effect of Germanium (Ge) subwavelength arrays designed in-plane with a normal incidence. Spectra of vertical electric field component normal to the surface show pronounced resonance peaks in an infrared range, which can be applied in a quantum well infrared photodetector. Unlike the near-field optics in metallic systems that are commonly related to surface plasmons, the intense vertical field along the surface of the Ge film can be interpreted as a combination of diffraction and waveguide theory. The existence of the enhanced field is confirmed by measuring the Fourier transform infrared spectra of fabricated samples. The positions of the resonant peaks obtained in experiment are in good agreement with our simulations. PMID- 24216890 TI - Deposited low temperature silicon GHz modulator. AB - We demonstrate gigahertz electro-optic modulator fabricated on low temperature polysilicon using excimer laser annealing technique compatible with CMOS backend integration. Carrier injection modulation at 3 Gbps is achieved. These results open up an array of possibilities for silicon photonics including photonics on DRAM and on flexible substrates. PMID- 24216891 TI - Transient radiative transfer in a scattering slab considering polarization. AB - The characteristics of the transient and polarization must be considered for a complete and correct description of short-pulse laser transfer in a scattering medium. A Monte Carlo (MC) method combined with a time shift and superposition principle is developed to simulate transient vector (polarized) radiative transfer in a scattering medium. The transient vector radiative transfer matrix (TVRTM) is defined to describe the transient polarization behavior of short-pulse laser propagating in the scattering medium. According to the definition of reflectivity, a new criterion of reflection at Fresnel surface is presented. In order to improve the computational efficiency and accuracy, a time shift and superposition principle is applied to the MC model for transient vector radiative transfer. The results for transient scalar radiative transfer and steady-state vector radiative transfer are compared with those in published literatures, respectively, and an excellent agreement between them is observed, which validates the correctness of the present model. Finally, transient radiative transfer is simulated considering the polarization effect of short-pulse laser in a scattering medium, and the distributions of Stokes vector in angular and temporal space are presented. PMID- 24216892 TI - Bending effect on modal interference in a fiber taper and sensitivity enhancement for refractive index measurement. AB - We demonstrate the bending effect of microfiber on interference fringes in a compact taper-based modal interferometer and sensitivity for refractive index (RI) measurement. For the bend curvature ranging from 0 to 0.283 mm(-1), the measured RI sensitivity distinctively increases from 342.5 nm/RIU (refractive index unit) to 1192.7 nm/RIU around RI = 1.333 and from 3847.1 nm/RIU to 11006.0 nm/RIU around RI = 1.430, respectively. Theoretical analysis reveals that such enhancement is determined by the dispersion property of the intermodal index rather than other parameters, such as the variation of the straightforward evanescent field. The magnitude of sensitivity varies as a function of the microfiber bend curvature. Approaching a critical curvature (the intermodal-index dispersion factor approaches zero), the sensitivity is significantly enhanced, exhibiting great potential in RI sensing areas. PMID- 24216893 TI - Near-infrared trapped mode magnetic resonance in an all-dielectric metamaterial. AB - Optical responses in conventional metamaterials based on plasmonic metal nanostructures are inevitably accompanied by Joule losses, which obstruct practical applications by limiting resonance quality factors and compromising the efficiency of metamaterial devices. Here we experimentally demonstrate a fully dielectric metamaterial that exhibits a 'trapped mode' resonance at optical frequencies, founded upon the excitation by incident light of anti-parallel displacement currents in meta-molecules comprising pairs of parallel, geometrically dissimilar dielectric nano-bars. The phenomenon is demonstrated in the near-infrared part of the spectrum using silicon, showing that in principle strong, lossless resonant responses are possible anywhere in the optical spectral range. PMID- 24216894 TI - Design of polarization-independent adiabatic splitters fabricated on silicon-on insulator substrates. AB - A novel design for a polarization-independent SOI-based 2 * 2 3-dB adiabatic splitter with sub-micron-scale dimensions is proposed and modeled. To achieve slow and smooth mode evolution, a structure with simultaneous tapering of velocity and coupling is used. To reduce the adiabatic region length by adjusting the gap separation, the coupling strengths of TE and TM polarizations as a function of the gap value are analyzed. For both polarizations, a high uniformity within +/- 0.2dB over a broad bandwidth from 1520 to 1650 nm is achieved with a 300-MUm-long adiabatic region. PMID- 24216895 TI - Combined cavity ring-down and spectrophotometry for measuring reflectance of optical laser components. AB - A combined cavity ring-down (CRD) and spectrophotometry technique is developed to measure with sufficiently high accuracy the reflectance of any practically fabricated optical laser component with reflectance ranging from below 0.01% to over 99.999%. In this combined technique, a CRD configuration is employed to measure reflectance higher than 99%, and a conventional spectrophotometric configuration, which is formed by simply removing the rear cavity mirror from the CRD configuration, is applied to measure reflectance below 99%. Uncertainties below 0.0001% for reflectance over 99.99% and below 0.3% for reflectance below 99% are experimentally achieved with CRD and spectrophotometry configurations, respectively, of one single experimental setup. PMID- 24216896 TI - Mode control and mode conversion in nonlinear aluminum nitride waveguides. AB - While single-mode waveguides are commonly used in integrated photonic circuits, emerging applications in nonlinear and quantum optics rely fundamentally on interactions between modes of different order. Here we propose several methods to evaluate the modal composition of both externally and device-internally excited guided waves and discuss a technique for efficient excitation of arbitrary modes. The applicability of these methods is verified in photonic circuits based on aluminum nitride. We control modal excitation through suitably engineered grating couplers and are able to perform a detailed study of waveguide-internal second harmonic generation. Efficient and broadband power conversion between orthogonal polarizations is realized within an asymmetric directional coupler to demonstrate selective excitation of arbitrary higher-order modes. Our approach holds promise for applications in nonlinear optics and frequency up/down-mixing in a chipscale framework. PMID- 24216897 TI - Information-rate analysis of a fiber-optic transmission system including 2R signal regenerators. AB - Performance of a single-channel fiber-optic transmission system in which signal regenerators are periodically inserted is analyzed in terms of information rate (IR) considering channel memory. Limitations in using regenerators in a system having non-zero residual dispersion between the regenerators are discussed. It is shown that a type of signal impairment caused by the interaction between the transmission-fiber dispersion and the regenerator nonlinearity is pattern dependent and will be mitigated by the use of sequence estimation after detection at the receiver. PMID- 24216898 TI - Near ultraviolet InGaN/AlGaN-based light-emitting diodes with highly reflective tin-doped indium oxide/Al-based reflectors. AB - The enhanced light output power of a InGaN/AlGaN-based light-emitting diodes (LEDs) using three different types of highly reflective Sn-doped indium oxide (ITO)/Al-based p-type reflectors, namely, ITO/Al, Cu-doped indium oxide (CIO)/s ITO(sputtered)/Al, and Ag nano-dots(n-Ag)/CIO/s-ITO/Al, is presented. The ITO/Al based reflectors exhibit lower reflectance (76 - 84% at 365 nm) than Al only reflector (91.1%). However, unlike Al only n-type contact, the ITO/Al-based contacts to p-GaN show good ohmic characteristics. Near-UV (365 nm) InGaN/AlGaN based LEDs with ITO/Al, CIO/s-ITO/Al, and n-Ag/CIO/s-ITO/Al reflectors exhibit forward-bias voltages of 3.55, 3.48, and 3.34 V at 20 mA, respectively. The LEDs with the ITO/Al and CIO/s-ITO/Al reflectors exhibit 9.5% and 13.5% higher light output power (at 20 mA), respectively, than the LEDs with the n-Ag/CIO/s-ITO/Al reflector. The improved performance of near UV LEDs is attributed to the high reflectance and low contact resistivity of the ITO/Al-based reflectors, which are better than those of conventional Al-based reflectors. PMID- 24216899 TI - Acousto-optic imaging of a color picture hidden behind a scattering layer. AB - An imaging technique has been developed to image a color picture hidden behind a 5 mm thick, highly scattering layer with low transmittance of 0.24%. Small vibrations (< 1 um) were induced in the hidden picture, causing a time-varying speckle pattern on the scattering layer in the front, which is captured by a CCD camera and quantified as speckle contrast difference (SCD). With two lasers at 543 nm and 633 nm, the imaging system raster-scans the front of the scattering layer and the resulting SCD image reveals the color features of the hidden picture. PMID- 24216900 TI - Rabi oscillations and self-induced transparency in InAs/InP quantum dot semiconductor optical amplifier operating at room temperature. AB - We report direct observations of Rabi oscillations and self-induced transparency in a quantum dot optical amplifier operating at room temperature. The experiments make use of pulses whose durations are shorter than the coherence time which are characterized using Cross-Frequency-Resolved Optical Gating. A numerical model which solves the Maxwell and Schrodinger equations and accounts for the inhomogeneously broadened nature of the quantum dot gain medium confirms the experimental results. The model is also used to explain the relationship between the observability of Rabi oscillations, the pulse duration and the homogeneous and inhomogeneous spectral widths of the semiconductor. PMID- 24216901 TI - Laser-manufactured mirrors for geometrical output coupling of intracavity generated high harmonics. AB - We demonstrate micro structuring of fused-silica laser mirror substrates by Inverse Laser Drilling. Slits of a width down to ~80 um and circular holes with diameters down to ~50 um have been structured into quarter-inch thick substrates. Except for chipping, the surface areas around these openings have not been irreversibly affected by the manufacturing process. The micro structured mirrors can be used for geometrical output coupling of coherent EUV radiation from cavity enhanced high harmonic generation. PMID- 24216902 TI - Multi-mode interferometer-based twist sensor with low temperature sensitivity employing square coreless fibers. AB - An all-fiber twist sensor based on multimode interferometer (MMI) has been proposed and fabricated by splicing both ends of a section of square no-core fiber (NCF) with a single mode fiber. We have investigated the transmission spectral characteristics of the square fiber under different applied twisting angles. Within a torsion angle range of -360 degrees ~360 degrees , the wavelength and transmission sensitivities are 1.28615 nm/(rad * m(-1)) and 0.11863%/ (rad * m(-1)), respectively. Moreover due to the trivial thermal expansion coefficient of pure silica fiber, the proposed twist sensor has a low temperature sensitivity, which is desirable to solve the temperature cross sensitivity. PMID- 24216903 TI - A single analytical model for sparkle and graininess patterns in texture of effect coatings. AB - Flakes in effect coatings, which are responsible for its color shift, are not perfectly horizontally oriented, producing a non uniform texture when observed from a distance of around one meter or less. If the coating is illuminated by a diffuse source, a granular appearance is observed, called graininess. But when the coating is illuminated by unidirectional light, some luminous spots on a dark background appear, effect that is known as sparkle. The characterization of these two textures is getting more important for automotive industry because of the high percentage of cars with effect coatings and because improvements in imaging technology allows this effect to be measured by, for instance, commercial instruments as BYK-mac. A single analytical model to understand and radiometrically characterize both sparkle and graininess in effect coatings is presented and studied in this work. It allows both patterns to be explained and, despite its simplicity, includes variables related to the optical system (Point Spread Function (PSF) and size of the entrance pupil), its distance to the coating, the diffusion grade of the illumination, the illumination and observation directions, and coating parameters. PMID- 24216904 TI - Optimal projector configuration design for 300-Mpixel multi-projection 3D display. AB - To achieve an immersive natural 3D experience on a large screen, a 300-Mpixel multi-projection 3D display that has a 100-inch screen and a 40 degrees viewing angle has been developed. To increase the number of rays emanating from each pixel to 300 in the horizontal direction, three hundred projectors were used. The projector configuration is an important issue in generating a high-quality 3D image, the luminance characteristics were analyzed and the design was optimized to minimize the variation in the brightness of projected images. The rows of the projector arrays were repeatedly changed according to a predetermined row interval and the projectors were arranged in an equi-angular pitch toward the constant central point. As a result, we acquired very smooth motion parallax images without discontinuity. There is no limit of viewing distance, so natural 3D images can be viewed from 2 m to over 20 m. PMID- 24216905 TI - Kilometer range filamentation. AB - We demonstrate for the first time the possibility to generate long plasma channels up to a distance of 1 km, using the terawatt femtosecond T&T laser facility. The plasma density was optimized by adjusting the chirp, the focusing and beam diameter. The interaction of filaments with transparent and opaque targets was studied. PMID- 24216906 TI - Room-temperature larger-scale highly ordered nanorod imprints of ZnO film. AB - Room-temperature large-scale highly ordered nanorod-patterned ZnO films directly integrated on III-nitride light-emitting diodes (LEDs) are proposed and demonstrated via low-cost modified nanoimprinting, avoiding a high-temperature process. with a 600 nm pitch on top of a critical 200 nm thick Imprinting ZnO nanorods of 200 nm in diameter and 200 nm in height continuous ZnO wetting layer, the light output power of the resulting integrated ZnO-nanorod-film/semi transparent metal/GaN/InGaN LED shows a two-fold enhancement (100% light extraction efficiency improvement) at the injection current of 150 mA, in comparison with the conventional LED without the imprint film. The increased optical output is well explained by the enhanced light scattering and outcoupling of the ZnO-rod structures along with the wetting film, as verified by the numerical simulations. The wetting layer is found to be essential for better impedance matching. The current-voltage characteristics and electroluminescence measurements confirm that there is no noticeable change in the electrical or spectral properties of the final LEDs after ZnO-nanorod film integration. These results suggest that the low-cost high-quality large-scale ZnO-nanorod imprints hold great promise for superior LED light extraction. PMID- 24216907 TI - Detuning in apodized point-by-point fiber Bragg gratings: insights into the grating morphology. AB - Point-by-point (PbP) inscription of fiber Bragg gratings using femtosecond laser pulses is a versatile technique that is currently experiencing significant research interest for fiber laser and sensing applications. The recent demonstration of apodized gratings using this technique provides a new avenue of investigation into the nature of the refractive index perturbation induced by the PbP modifications, as apodized gratings are sensitive to variation in the average background index along the grating. In this work we compare experimental results for Gaussian- and sinc-apodized PbP gratings to a coupled-mode theory model, demonstrating that the refractive index perturbation induced by the PbP modifications has a negative contribution to the average background index which is small, despite the presence of strong reflective coupling. By employing Fourier analysis to a simplified model of an individual modification, we show that the presence of a densified shell around a central void can produce strong reflective coupling with near-zero change in the average background index. This result has important implications for the experimental implementation of apodized PbP gratings, which are of interest for a range of fiber laser and fiber sensing technologies. PMID- 24216908 TI - Bound state vector solitons with locked and precessing states of polarization. AB - We report experimental observation of new tightly and loosely bound state vector solitons with locked and precessing states of polarization in a carbon nanotube mode locked fiber laser in the anomalous dispersion regime. PMID- 24216909 TI - Linear segmentation algorithm for detecting layer boundary with lidar. AB - The automatic detection of aerosol- and cloud-layer boundary (base and top) is important in atmospheric lidar data processing, because the boundary information is not only useful for environment and climate studies, but can also be used as input for further data processing. Previous methods have demonstrated limitations in defining the base and top, window-size setting, and have neglected the in layer attenuation. To overcome these limitations, we present a new layer detection scheme for up-looking lidars based on linear segmentation with a reasonable threshold setting, boundary selecting, and false positive removing strategies. Preliminary results from both real and simulated data show that this algorithm cannot only detect the layer-base as accurate as the simple multi-scale method, but can also detect the layer-top more accurately than that of the simple multi-scale method. Our algorithm can be directly applied to uncalibrated data without requiring any additional measurements or window size selections. PMID- 24216910 TI - Experimental demonstration of 24-Gb/s CAP-64QAM radio-over-fiber system over 40 GHz mm-wave fiber-wireless transmission. AB - We propose and demonstrate a novel CAP-ROF system based on multi-level carrier less amplitude and phase modulation (CAP) 64QAM with high spectrum efficiency for mm-wave fiber-wireless transmission. The performance of novel CAP modulation with high order QAM, for the first time, is investigated in the mm-wave fiber-wireless transmission system. One I/Q modulator is used for mm-wave generation and base band signal modulation based on optical carrier suppression (OCS) and intensity modulation. Finally, we demonstrated a 24-Gb/s CAP-64QAM radio-over-fiber (ROF) system over 40-km stand single-mode-fiber (SMMF) and 1.5-m 38-GHz wireless transmission. The system operation factors are also experimentally investigated. PMID- 24216911 TI - Angle-multiplexed spatial-spectral interferometry for simultaneous measurement of spectral phase and polarization state. AB - A novel method to simultaneously extract the polarization state and relative spectral phase of an ultrashort laser pulse from an angle-multiplexed spatial spectral interferometric measurement is proposed and experimentally demonstrated. Spectral interference is produced between an arbitrary polarized signal pulse and two orthogonal linearly polarized reference pulses. The accuracy of this technique has been verified by reconstructing the known relative spectral phase arising from material dispersion and the known elliptical polarization state. Measurement of the relative spectral phase and the spatially variable polarization state of a radially polarized pulse is also demonstrated. An additional independent measurement of the spectral phase of reference pulses provides absolute spectral and temporal characteristics of the signal pulse. PMID- 24216912 TI - Slotted photonic crystal nanobeam cavity with parabolic modulated width stack for refractive index sensing. AB - We present the design, fabrication, and the characterization of high-Q slotted 1D photonic crystal (PhC) cavities with parabolic-width stack. Their peculiar geometry enables the location of the resonating mode close to the air-band. The majority of optical field distributes in the slotted low-index area and the light matter interaction with the analytes has been enhanced. Cavities with measured Q factors ~10(4) have been demonstrated. The refractive index sensing measurement for NaCl solutions with different concentrations shows a sensitivity around 410. Both the achieved Q-factor and the sensitivity are higher than the one reported recently by using 2D slotted PhC cavities. The total size for the sensing part of the present device is reduced to 16.8 * 2.5 MUm(2). PMID- 24216913 TI - Enhanced contrast ratio and viewing angle of polymer-stabilized liquid crystal via refractive index matching between liquid crystal and polymer network. AB - Long standing electro-optic problems of a polymer-dispersed liquid crystal (PDLC) such as low contrast ratio and transmittances decrease in oblique viewing angle have been challenged with a mixture of dual frequency liquid crystal (DFLC) and reactive mesogen (RM). The DFLC and RM molecules were vertically aligned and then photo-polymerized using a UV light. At scattering state under 50 kHz electric field, DFLC was switched to planar state, giving greater extraordinary refractive index than the normal PDLC cell. Consequently, the scattering intensity and the contrast ratio were increased compared to the conventional PDLC cell. At transparent state under 1 kHz electric field, the extraordinary refractive index of DFLC was simultaneously matched with the refractive index of vertically aligned RM so that the light scattering in oblique viewing angles was minimized, giving rise to high transmittance in all viewing angles. PMID- 24216914 TI - Modulation of laser induced-cracks inside a LiF single crystal by fs laser irradiation at multiple points. AB - Crack formations inside a LiF single crystal after femtosecond laser irradiation at multiple points were investigated. In the case of sequential laser irradiation at three points, the propagations of some cracks were prevented by the dislocation bands generated by the previous laser irradiation. On the other hand, in the case of simultaneous laser irradiation at three points with a spatial light modulator, cracks in all the <100> directions from the photoexcited regions were generated clearly, but the length of one crack depended on the distribution of laser irradiation positions. The simulation of elastic dynamics after fs laser irradiation at three points elucidated that the interference of laser induced stress waves depended on the distributions of the irradiation positions. We found that the constructive interference of stress waves at a crack tip should have prevented the crack from propagating further and the tensile stress by destructive interference of stress waves along a crack should have facilitated the propagation of the crack. PMID- 24216915 TI - Impact of cavity spectrum on span in microresonator frequency combs. AB - We experimentally study the factors that limit the span in frequency combs derived from the crystalline whispering gallery mode resonators. We observe that cavity dispersion is the key property that governs the parameters of the combs resulting from cascaded four wave mixing process. Two different regimes of comb generation are observed depending on the precise cavity dispersion behavior at the pump wavelength. In addition, the comb generation efficiency is found to be affected by the crossing of modes of different families. The influence of Raman lasing and its dependence on temperature is discussed. PMID- 24216916 TI - A laterally-coupled distributed feedback laser with equivalent quarter-wave phase shift. AB - We report the first laterally-coupled distributed feedback (LC-DFB) laser with a quarter-wave equivalent phase shift (EPS) realized by interference lithography (IL) and conventional photolithography. A specially designed sampled grating is fabricated on both sidewalls of a ridge waveguide to provide a quarter-wave EPS at the center of the cavity. The resulting laser exhibits stable single-mode lasing operation over a wide range of injection currents, with a side mode suppression ratio (SMSR) of 41.1 dB. This provides a practical, low-cost method to fabricate quarter-wave phase shifted DFB lasers with high performance without any epitaxial regrowth or the use of electron-beam lithography, thereby simplifying the fabrication of DFB lasers with stable and precise wavelengths, as single devices or as arrays in photonic integrated circuits. PMID- 24216917 TI - Nanobubble evolution around nanowire in liquid. AB - The evolution of the shape and size of a bubble around a nanowire immersed in a liquid can be studied as a light absorption problem and consequently can directly be related to the distribution of the temperature around the nanowire. Such a physical phenomenon can be seen as the photo-thermal coupled problem of nanowire illuminated by an electromagnetic wave. The resolution of the multiphysic model allows to compute the variation of the temperature and consequently the evolution of the created bubble. An advanced adaptive remeshing process is developed to solve the numerical model using Finite Element Method. An optimization process is applied to solve the coupled problem and is used to detect the size of the produced bubble around nanowire under illumination. The adaptive remeshing process permits to control the convergence of the numerical solution relatively to the evolution of the temperature field. The process allows to study the evolution of the shape and size of the bubble. We show the influence of the laser parameters on the evolution of the bubble. The informations about the geometry of the nanowire can be deduced from the size and shape of the bubble. PMID- 24216918 TI - Laser operation of diode-pumped Er,Yb co-doped YAG ceramics at 1.6 MUm. AB - 1.6 MUm eye-safe emission of a diode pumped Er,Yb co-doped YAG ceramic laser is firstly demonstrated. Operation of the ceramic laser under different ceramic sample lengths, co-doping concentrations and control temperatures were experimentally investigated. A maximum output power of 222 mW was achieved at an absorbed pump power of 8.1 W, corresponding to a conversion efficiency of 2.74%. Laser emission at 1.05 MUm for transition of the Yb(3+) ions was also studied on the same ceramic samples. The results clearly show the existence of resonantly energy transfer from the Yb(3+) ions to Er(3+) ions. PMID- 24216919 TI - A cost-effective 25-Gb/s EML TOSA using all-in-one FPCB wiring and metal optical bench. AB - We present a cost-effective 25-Gb/s electro-absorption modulator integrated laser (EML) transmitter optical sub-assembly (TOSA) using all-in-one flexible printed circuit board (FPCB) wiring and a metal optical bench (MOB). For a low cost and high bandwidth TOSA, internal and external wirings and feed-through of the TOSA to transmit radio-frequency (RF) signal are configured all-in-one using the FPCB. The FPCB is extended from an exterior of the TOSA package up to an EML chip inside the package through the slit formed on a rear sidewall of the package and die-bonded on the MOB. The EML TOSA shows a modulated output power of more than 3.5 dBm and a clear eye pattern with a dynamic extinction ratio of ~8.4 dB at a data rate of 25.78 Gb/s. PMID- 24216920 TI - A slim apparatus of transferring discrete LEDs' light into an ultra-collimated planar light source. AB - In this paper, we proposed a novel apparatus, which has very slim volume and can transfer light emitted from discrete LEDs into a uniform and ultra-collimated planar light source (UCPLS). This apparatus adopts the two-layer folded frame and two-stage CPC design so that thickness of the entire apparatus can be minimized; especially the feeder in the two-stage CPC design can greatly reduce the thickness of the CPC and make the light passing through the second-stage CPC become much more collimated. In addition, by side-by-side arrangement, a large sized UCPLS can also be obtained. In our embodiment with an emitting area of the upper LGP of 280 mmX80 mm and a LED with optical flux of 8 lumens used as the light source, the performance according to the related simulation results shows as follows: angular FWHM of the resultant light emitted from the apparatus in the vertical and horizontal is 4.87 degrees and 24 degrees, respectively; spatial uniformity and total energy efficiency reach 84% and 69%, respectively; the average head-on luminance reaches up 5600 nit, yet this apparatus consumes just 60 mW. Furthermore, the results also demonstrate this design has potential to be applied to the product of 23 inches above while thickness of the entire apparatus is only 2.2 mm. PMID- 24216921 TI - Transverse mode discrimination in long-wavelength wafer-fused vertical-cavity surface-emitting lasers by intra-cavity patterning. AB - Transverse mode discrimination is demonstrated in long-wavelength wafer-fused vertical-cavity surface-emitting lasers using ring-shaped air gap patterns at the fused interface between the cavity and the top distributed Bragg reflector. A significant number of devices with varying pattern dimensions was investigated by on-wafer mapping, allowing in particular the identification of a design that reproducibly increases the maximal single-mode emitted power by about 30 %. Numerical simulations support these observations and allow specifying optimized ring dimensions for which higher-order transverse modes are localized out of the optical aperture. These simulations predict further enhancement of the single mode properties of the devices with negligible penalty on threshold current and emitted power. PMID- 24216922 TI - Experimental demonstration of elastic optical networks based on enhanced software defined networking (eSDN) for data center application. AB - Due to the high burstiness and high-bandwidth characteristics of the applications, data center interconnection by elastic optical networks have attracted much attention of network operators and service providers. Many data center applications require lower delay and higher availability with the end-to end guaranteed quality of service. In this paper, we propose and implement a novel elastic optical network based on enhanced software defined networking (eSDN) architecture for data center application, by introducing a transport-aware cross stratum optimization (TA-CSO) strategy. eSDN can enable cross stratum optimization of application and elastic optical network stratum resources and provide the elastic physical layer parameter adjustment, e.g., modulation format and bandwidth. We have designed and verified experimentally software defined path provisioning on our testbed with four real OpenFlow-enabled elastic optical nodes for data center application. The overall feasibility and efficiency of the proposed architecture is also experimentally demonstrated and compared with individual CSO and physical layer adjustment strategies in terms of path setup/release/adjustment latency, blocking probability and resource occupation rate. PMID- 24216923 TI - 12.5 pm/V hybrid silicon and lithium niobate optical microring resonator with integrated electrodes. AB - We present a silicon microring resonator with a lithium niobate top cladding and integrated tuning electrodes. Submicrometer thin films of z-cut lithium niobate are bonded to silicon microring resonators via benzocyclobutene. Integrated electrodes are incorporated to confine voltage controlled electric fields within the lithium niobate thin film. The electrode design utilizes thin film metal electrodes and an optically transparent electrode wherein the silicon waveguide core serves as both an optical waveguide medium and as a conductive electrode medium. The hybrid material system combines the electro-optic functionality of lithium niobate with the high index contrast of silicon waveguides, enabling compact low tuning voltage microring resonators. Optical characterization of fabricated devices results in a measured loaded quality factor of 11,500 and a free spectral range of 7.15 nm in the infrared. The demonstrated tunability is 12.5 pm/V, which is over an order of magnitude greater than electrode-free designs. PMID- 24216924 TI - Pulse width shaping of passively mode-locked soliton fiber laser via polarization control in carbon nanotube saturable absorber. AB - We report the continuous control of the pulse width of a passively mode-locked fiber laser via polarization state adjustment in a single-walled carbon nanotube saturable absorber (SWCNT-SA). The SWCNT, coated on the side-polished fiber, was fabricated with optimized conditions and used for stable mode-locking of the fiber laser without Q-switching instabilities for any polarization state of the laser intra-cavity. The 3-dB spectral bandwidth of the mode-locked pulses can be continuously tuned from 1.8 nm to 8.5 nm with the polarization control for a given laser cavity length and applied pump power. A pulse duration varying from 470 fs to 1.6 ps was also observed with a change in the spectral bandwidth. The linear and the nonlinear transmission properties of the SA were analyzed, and found to exhibit different modulation depths depending on the input polarization state in the SA. The largest modulation depth of the SA was observed at the polarization state of the transverse electric mode that delivers shortest pulses at the laser output. PMID- 24216925 TI - Background-free millimeter-wave ultra-wideband signal generation based on a dual parallel Mach-Zehnder modulator. AB - A novel scheme for photonic generation of a millimeter-wave ultra-wideband (MMW UWB) signal is proposed and experimentally demonstrated based on a dual-parallel Mach-Zehnder modulator (DPMZM). In the proposed scheme, a single-frequency radio frequency (RF) signal is applied to one sub-MZM of the DPMZM to achieve optical suppressed-carrier modulation, and an electrical control pulse train is applied to the other sub-MZM biased at the minimum transmission point, to get an on/off switchable optical carrier. By filtering out the optical carrier with one of the first-order sidebands, and properly setting the amplitude of the control pulse, an MMW-UWB pulse train without the residual local oscillation is generated after photo-detection. The generated MMW-UWB signal is background-free, because the low frequency components in the electrical spectrum are effectively suppressed. In the experiment, an MMW-UWB pulse train centered at 25 GHz with a 10-dB bandwidth of 5.5 GHz is successfully generated. The low frequency components are suppressed by 22 dB. PMID- 24216926 TI - Dengue immunoassay with an LSPR fiber optic sensor. AB - Dengue fever is a viral disease that affects millions of people worldwide. Specific tests for dengue are not usually performed due to high costs, complicated procedures and, in some cases, long time to yield a result. For widespread use of specific tests to be possible, fast, reliable and fairly simple methods are needed. In this paper, we present a new dengue diagnostic method for the acute phase of the infection. The method proposed uses an all-optical fiber sensor based on Localized Surface Plasmon Resonance (LSPR) and specular reflection from gold nanoparticles (AuNPs). Dengue anti-NS1 antibody was immobilized on AuNPs deposited on the endface of a standard multimode fiber (62.5 um/125 um). The sensor is able to detect NS1 antigen at different concentrations, with limit of quantification estimated to be 0.074 MUg/ml = 1.54 nM. These results indicate that the sensor could potentially be used for dengue diagnosis in the acute phase of the infection. PMID- 24216927 TI - The polarization properties of a tilted polarizer. AB - Polarizers are key components in optical science and technology. Thus, understanding the action of a polarizer beyond oversimplifying approximations is crucial. In this work, we study the interaction of a polarizing interface with an obliquely incident wave experimentally. To this end, a set of Mueller matrices is acquired employing a novel procedure robust against experimental imperfections. We connect our observation to a geometric model, useful to predict the effect of polarizers on complex light fields. PMID- 24216928 TI - Robust, frequency-stable and accurate mid-IR laser spectrometer based on frequency comb metrology of quantum cascade lasers up-converted in orientation patterned GaAs. AB - We demonstrate a robust and simple method for measurement, stabilization and tuning of the frequency of cw mid-infrared (MIR) lasers, in particular of quantum cascade lasers. The proof of principle is performed with a quantum cascade laser at 5.4 um, which is upconverted to 1.2 um by sum-frequency generation in orientation-patterned GaAs with the output of a standard high-power cw 1.5 um fiber laser. Both the 1.2 um and the 1.5 um waves are measured by a standard Er:fiber frequency comb. Frequency measurement at the 100 kHz-level, stabilization to sub-10 kHz level, controlled frequency tuning and long-term stability are demonstrated. PMID- 24216929 TI - Suppression of amplitude-to-phase noise conversion in balanced optical-microwave phase detectors. AB - We demonstrate an amplitude-to-phase (AM-PM) conversion coefficient for a balanced optical-microwave phase detector (BOM-PD) of 0.001 rad, corresponding to AM-PM induced phase noise 60 dB below the single-sideband relative intensity noise of the laser. This enables us to generate 8 GHz microwave signals from a commercial Er-fibre comb with a single-sideband residual phase noise of -131 dBc Hz(-1) at 1 Hz offset frequency and -148 dBc Hz(-1) at 1 kHz offset frequency. PMID- 24216930 TI - Second harmonic generation correlation spectroscopy for single molecule experiments. AB - We demonstrate a single molecule detection approach to further extend the detection limit of correlation spectroscopic techniques through the Second Harmonic Generation Correlation Spectroscopy (SHGCS). SHG signals with high signal-to-noise ratio (SNR) were obtained from Barium titanium oxide, BaTiO(3) (BTO) nanocrystals (NCs) upon excitation by a femto-second laser fitted to the scanning confocal bench. The fluctuation of SHG signals from BTO NCs in transparent and turbid media was examined and their diffusion time and particle concentration were evaluated by autocorrelation. Proof-of-concept measurements indicate that water-dispersed BTO NCs at different concentrations yield an average diffusion time of 6.43 +/- 0.68 ms and the detection limit of SHGCS was found to be at 814 +/- 41 fM, approximately 100 folds below the detection limit of fluorescence correlation spectroscopy (FCS). The dynamics of BTO NCs was demonstrated in serum with high SNR and selectivity to show its potential applicability in biomedicine. High SNR and the sub-picomolar detection limit positions SHGCS as an excellent technique for ultralow single particle or single molecule experimentation in a complex medium. PMID- 24216931 TI - Volumetric display using rotating prism sheets arranged in a symmetrical configuration. AB - A volumetric display that creates a distortion-free three-dimensional (3D) image in midair is described. The proposed system consists of rotating prism sheets used as an optical scanner and a dihedral corner reflector array (DCRA), which is a distortion-free imaging element. Two prism sheets are arranged in a symmetrical configuration to reduce an unnatural motion parallax caused by optical aberrations. A cross-section of the 3D image is formed by the DCRA in midair and moved by the rotating prism sheets to create a 3D displayable space. A 3D volume image was displayed without image distortion or unnatural motion parallax. PMID- 24216932 TI - Wave-breaking-free pulse in an all-fiber normal-dispersion Yb-doped fiber laser under dissipative soliton resonance condition. AB - We reported on the dissipative soliton resonance (DSR) phenomenon in a mode locked Yb-doped fiber laser by using the nonlinear polarization rotation technique. It was found that the multi-pulse oscillation under high pump power could be circumvented by properly adjusting the polarization controllers, namely, the wave-breaking-free rectangular pulse in DSR region was achieved. As the DSR signature, the pulse duration varied from 8.8 ps to 22.92 ns with the increasing pump power. Correspondingly, the maximum pulse energy was 3.24 nJ. The results demonstrated that the DSR phenomenon could exist in Yb-doped fiber lasers, which could be used to achieve wave-breaking-free, ultrahigh-energy pulse. PMID- 24216933 TI - Shaping the evanescent field of optical nanofibers for cold atom trapping. AB - We investigate trapping geometries for cold, neutral atoms that can be created in the evanescent field of a tapered optical fibre by combining the fundamental mode with one of the next lowest possible modes, namely the HE(21) mode. Counter propagating red-detuned HE(21) modes are combined with a blue-detuned HE(11) fundamental mode to form a potential in the shape of four intertwined spirals. By changing the polarization from circular to linear in each of the two counter propagating HE(21) modes simultaneously the 4-helix configuration can be transformed into a lattice configuration. The modification to the 4-helix configuration due to unwanted excitation of the the TE(01) and TM(01) modes is also discussed. PMID- 24216934 TI - High-voltage thin-film GaN LEDs fabricated on ceramic substrates: the alleviated droop effect at 670 W/cm(2). AB - High-voltage thin-film GaN LEDs with the emission wavelength of 455 nm were fabricated on ceramic substrates (230 W/m . K). The high-voltage operation was achieved by three cascaded sub-LEDs with dielectric passivation and metal bridges conformally deposited on the side walls. Under the driving power of 670 W/cm(2), the high-voltage LEDs exhibit much alleviated efficiency droop and the operative temperature below 80 degrees C. The excellent performances were attributed to the improved current spreading within each sub-LED and the superior heat sinking of the ceramic substrate. PMID- 24216935 TI - Sensitivity enhanced strain and temperature measurements based on FBG and frequency chirp magnification. AB - In this work, highly sensitive measurements of strain and temperature have been demonstrated using a fiber Bragg grating (FBG) sensor with significantly enhance sensitivity by all-optical signal processing. The sensitivity enhancement is achieved by degenerated Four Wave Mixing (FWM) for frequency chirp magnification (FCM), which can be used for magnifying the wavelength drift of the FBG sensor induced by strain and temperature change. Highly sensitive measurements of static strain and temperature have been experimentally demonstrated with strain sensitivity of 5.36 pm/MUepsilon and temperature sensitivity of 54.09 pm/ degrees C. The sensitivity has been enhanced by a factor of five based on a 4-order FWM in a highly nonlinear fiber (HNLF). PMID- 24216936 TI - Polarization delivery in heterodyne interferometry. AB - Optically heterodyned laser interferometry, as applied to measuring linear displacements, requires different optical frequencies to be encoded onto unique polarization states. To eliminate non-linear contributions to the interferometer signal, the frequency difference must be introduced after beam splitting and the interfering beams must be recombined via spatially separated paths. The polarization jitter of the frequency-shifted beams still originates a noise in the beat-signal phase. A formula is given expressing the noise amplitude in terms of the illuminating beam's extinction ratio. PMID- 24216937 TI - Haze effect removal from image via haze density estimation in optical model. AB - Images/videos captured from optical devices are usually degraded by turbid media such as haze, smoke, fog, rain and snow. Haze is the most common problem in outdoor scenes because of the atmosphere conditions. This paper proposes a novel single image-based dehazing framework to remove haze artifacts from images, where we propose two novel image priors, called the pixel-based dark channel prior and the pixel-based bright channel prior. Based on the two priors with the haze optical model, we propose to estimate atmospheric light via haze density analysis. We can then estimate transmission map, followed by refining it via the bilateral filter. As a result, high-quality haze-free images can be recovered with lower computational complexity compared with the state-of-the-art approach based on patch-based dark channel prior. PMID- 24216938 TI - Characterization and improvement of three-dimensional imaging performance of GRIN lens-based two-photon fluorescence endomicroscopes with adaptive optics. AB - Inherent aberrations of gradient index (GRIN) lenses used in fluorescence endomicroscopes deteriorate imaging performance. Using adaptive optics, we characterized and corrected the on-axis and off-axis aberrations of a GRIN lens with NA 0.8 at multiple focal planes. We demonstrated a rotational-transformation based correction procedure, which enlarged the imaging area with diffraction limited resolution with only two aberration measurements. 204.8 * 204.8 um2 images of fluorescent beads and brain slices before and after AO corrections were obtained, with evident improvements in both image sharpness and brightness after AO correction. These results show great promises of applying adaptive optical two-photon fluorescence endomicroscope to three-dimensional (3D) imaging. PMID- 24216939 TI - Frequency stabilized coherent Brillouin random fiber laser: theory and experiments. AB - A coherent random fiber laser based on stimulated Brillouin scattering as gain and Rayleigh scattering as distributed feedback mirror was constructed. Its frequency is stabilized by a high finesse narrow-band Fabry-Perot interferometer (FPI) to select lasing frequency within the gain bandwidth. The light confinement within single-mode fiber enhances largely the random lasing directionality, which enables a high-quality coherent random lasing in the weak scattering region by using a milliwatt continuous-wave pump source. The FPI in the laser configuration acts as a frequency selection on the Rayleigh feedback light, and thus the random lasing frequency was locked at one of its transmission peaks giving a relative frequency fluctuation of ~2.5 * 10(-11) at 100 s. The measured frequency jitter is within ~~ +/- 20 kHz over 3 hours, 3 dB linewidth is ~50 Hz and frequency noise is ~20 mHz/Hz(1/2) at 10 kHz. PMID- 24216940 TI - Sub-millisecond timing-jitter-free tuning of parametric dispersion compensator. AB - We demonstrate sub-millisecond tuning of a prototype parametric tunable dispersion compensator (P-TDC) based on cascaded polarization-diverse four-wave mixing (FWM) process with a fast tunable and highly wavelength-stable pump light source. The pump light source is developed using a tunable distributed amplification chirped sampled grating distributed reflector laser that is fully wavelength tunable by on-chip heaters with a 3-dB frequency response of 45 kHz, resulting in fast dispersion tuning of less than 50 MUs without additional timing jitter. The P-TDC is developed as the first prototype to satisfy essential requirements for practical network uses: stable input-polarization diversity, input-wavelength preservation, and seamless dispersion tunability for entire C band input wavelengths are simultaneously achieved. PMID- 24216941 TI - Low-filling-factor superconducting single photon detector with high system detection efficiency. AB - We designed, fabricated, and measured superconducting nanowire single-photon detectors (SSPDs) with low filling factor which achieve high system detection efficiency (SDE) and counting rate simultaneously. Numerical simulation reveals that high optical absorptance is possible in SSPDs even for low filing factor by tuning the device design. The SDEs of fabricated 18-50% filling factor SSPDs were measured systematically, and all SSPDs showed high SDEs of 61-80% and the lowest 18% filling factor SSPD achieved a high SDE of 69%. PMID- 24216942 TI - Information-based analysis of X-ray in-line phase tomography with application to the detection of iron oxide nanoparticles in the brain. AB - The study analyzes noise in X-ray in-line phase tomography in a biomedical context. The impact of noise on detection of iron oxide nanoparticles in mouse brain is assessed. The part of the noise due to the imaging system and the part due to biology are quantitatively expressed in a Neyman Pearson detection strategy with two models of noise. This represents a practical extension of previous work on noise in phase-contrast X-ray imaging which focused on the theoretical expression of the signal-to-noise ratio in mono-dimensional phantoms, taking account of the statistical noise of the imaging system only. We also report the impact of the phase retrieval step on detection performance. Taken together, this constitutes a general methodology of practical interest for quantitative extraction of information from X-ray in-line phase tomography, and is also relevant to assessment of contrast agents with a blob-like signature in high resolution imaging. PMID- 24216943 TI - Integrated photonic building blocks for next-generation astronomical instrumentation II: the multimode to single mode transition. AB - There are numerous advantages to exploiting diffraction-limited instrumentation at astronomical observatories, which include smaller footprints, less mechanical and thermal instabilities and high levels of performance. To realize such instrumentation it is imperative to convert the atmospheric seeing-limited signal that is captured by the telescope into a diffraction-limited signal. This process can be achieved photonically by using a mode reformatting device known as a photonic lantern that performs a multimode to single-mode transition. With the aim of developing an optimized integrated photonic lantern, we undertook a systematic parameter scan of devices fabricated by the femtosecond laser direct write technique. The devices were designed for operation around 1.55 MUm. The devices showed (coupling and transition) losses of less than 5% for F/# >= 12 injection and the total device throughput (including substrate absorption) as high as 75-80%. Such devices show great promise for future use in astronomy. PMID- 24216944 TI - Fano resonances in integrated silicon Bragg reflectors for sensing applications. AB - We investigate theoretically and experimentally Fano resonances in integrated silicon Bragg reflectors. These asymmetric resonances are obtained by interference between light reflected from the Bragg waveguide and from the end facet. The Bragg reflectors were designed and modeled using the 1D transfer matrix method, and they were fabricated in standard silicon wafers using a CMOS compatible process. The results show that the shape and asymmetry of the Fano resonances depend on the relative phase of the reflected light from the Bragg reflectors and end facet. This phase relationship can be controlled to optimize the lineshapes for sensing applications. Temperature sensing in these integrated Bragg reflectors are experimentally demonstrated with a temperature sensitivity of 77 pm/ degrees C based on the thermo-optic effect of silicon. PMID- 24216945 TI - Mode-expansion theory for inhomogeneous meta-surfaces. AB - Modeling meta-surfaces as thin metamaterial layers with continuously varying bulk parameters, we employed a rigorous mode-expansion theory to study the scattering properties of such systems. We found that a meta-surface with a linear reflection phase profile could redirect an impinging light to a non-specular channel with nearly 100% efficiency, and a meta-surface with a parabolic reflection-phase profile could focus incident plane wave to a point image. Under certain approximations, our theory reduces to the local response model (LRM) established for such problems previously, but our full theory has overcome the energy non conservation problems suffered by the LRM. Microwave experiments were performed on realistic samples to verify the key theoretical predictions, which match well with full-wave simulations. PMID- 24216946 TI - Nanowatt threshold, alumina sensitized neodymium laser integrated on silicon. AB - Low threshold lasers based on rare-earth elements have enabled numerous scientific discoveries and innovations in industry. However, pushing the threshold into the sub-microwatt regime has been stymied by a fundamental material phenomenon. Specifically, rare earth dopants form clusters which quench emission and reduce efficiency. Here, we fabricate resonant cavity lasers from neodymium-doped silica films containing alumina. The alumina prevents the clustering of the Neodymium, enabling the lasers to achieve thresholds of 530 nanoWatts at room temperature. PMID- 24216947 TI - Electromagnetic cosine-Gaussian Schell-model beams in free space and atmospheric turbulence. AB - A recently introduced class of scalar cosine-Gaussian Schell-Model [CGSM] beams is generalized to electromagnetic theory. The realizability conditions and the beam conditions on the source parameters are derived. Analytical formulas for the cross-spectral density matrix elements of the electromagnetic cosine-Gaussian Schell-model [EM CGSM] beams propagating in isotropic random medium are derived. It is found that the EM CGSM beams possess single-ring or double-ring intensity profiles, depending of source parameters. As two examples, the statistical characteristics of the EM CGSM beams propagating in free space and non-Kolmogorov turbulent atmosphere are studied numerically. The effects of the fractal constant of the atmospheric spectrum and the refractive-index structure constant on such characteristics are analyzed in detail. PMID- 24216948 TI - Entanglement-based quantum key distribution with biased basis choice via free space. AB - We report a free-space entanglement-based quantum key distribution experiment, implementing the biased basis protocol between two sites which are 15.3 km apart. Photon pairs from a polarization-entangled source are distributed through two 7.8 km free-space optical links. An optimal bias 20:80 between the X and Z basis is used. A post-processing scheme with finite-key analysis is applied to extract the final secure key. After three-hour continuous operation at night, a 4293-bit secure key is obtained, with a final key rate of 0.124 bit per raw key bit which increases the final key rate by 14.8% comparing to the standard BB84 case. Our results experimentally demonstrate that the efficient BB84 protocol, which increases key generation efficiency by biasing Alice and Bob's basis choices, is potentially useful for the ground-satellite quantum communication. PMID- 24216949 TI - Two-kernel image deconvolution. AB - A method for deconvolution of the true image of an object from two recorded images is proposed. These two images have to be made by an imaging system with two different but interconnected kernels. The method is formulated as a system of Fredholm equations of the first kind reduced to a single functional equation in Fourier space. The kernels of the system and the true image of an object are found from the same recorded images. PMID- 24216950 TI - Control of forward stimulated polariton scattering in periodically-poled KTP crystals. AB - We report suppression of forward stimulated polariton scattering (SPS) in chi((2)) structured media. Periodic poling in KTiOPO(4) (KTP) leads to the destructive interference of phonon-polariton waves, which is responsible for the dependence of the SPS threshold on the poling period. This was confirmed by comparing the SPS thresholds in periodically-poled KTP (PPKTP) crystals with different poling periods. Further confirming the physical picture, we studied the changes in the Stokes power distribution as a function of the rotation angle of the PPKTP crystal. PMID- 24216951 TI - Design of a spherical focal surface using close-packed relay optics: erratum. AB - A coding error was found in calculating the optimal packing distribution of our geodesic array. The error was corrected and the new optimization results in slightly improved packing density. The overall approach and algorithm remain unchanged. PMID- 24216952 TI - Focus issue on surface plasmon photonics introduction. AB - The 6th International Conference on Surface Plasmon Photonics (SPP6) was held in Ottawa, Canada from May 26th to 31st, 2013. This independent series of biennial conferences is widely regarded as the premier series in the field, and the 6th edition maintained the tradition of excellence. This Focus Issue collects several papers related to research presented at SPP6, and although the number of papers it comprises is small compared to the total number of papers presented at the conference, the issue is representative and provides a good snapshot of the field at this point in time. PMID- 24216953 TI - Nanosecond thermo-optical dynamics of polymer loaded plasmonic waveguides. AB - The thermo-optical dynamics of polymer loaded surface plasmon waveguide (PLSPPW) based devices photo-thermally excited in the nanosecond regime is investigated. We demonstrate thermo-absorption of PLSPPW modes mediated by the temperature dependent ohmic losses of the metal and the thermally controlled field distribution of the plasmon mode within the metal. For a PLSPPW excited by sub nanosecond long pulses, we find that the thermo-absorption process leads to modulation depths up to 50% and features an activation time around 2 ns whereas the relaxation time is around 800 ns, four-fold smaller than the cooling time of the metal film itself. Next, we observe the photo-thermal activation of PLSPPW racetrack shaped resonators at a time scale of 300 ns followed however by a long cooling time (18 MUs) attributed to the poor heat diffusivity of the polymer. We conclude that nanosecond excitation combined to high thermal diffusivity materials opens the way to high speed thermo-optical plasmonic devices. PMID- 24216954 TI - Quantum effects and nonlocality in strongly coupled plasmonic nanowire dimers. AB - Using a fully quantum mechanical approach we study the optical response of a strongly coupled metallic nanowire dimer for variable separation widths of the junction between the nanowires. The translational invariance of the system allows to apply the time-dependent density functional theory (TDDFT) for nanowires of diameters up to 10 nm which is the largest size considered so far in quantum modeling of plasmonic dimers. By performing a detailed analysis of the optical extinction, induced charge densities, and near fields, we reveal the major nonlocal quantum effects determining the plasmonic modes and field enhancement in the system. These effects consist mainly of electron tunneling between the nanowires at small junction widths and dynamical screening. The TDDFT results are compared with results from classical electromagnetic calculations based on the local Drude and non-local hydrodynamic descriptions of the nanowire permittivity, as well as with results from a recently developed quantum corrected model. The latter provides a way to include quantum mechanical effects such as electron tunneling in standard classical electromagnetic simulations. We show that the TDDFT results can be thus retrieved semi-quantitatively within a classical framework. We also discuss the shortcomings of classical non-local hydrodynamic approaches. Finally, the implications of the actual position of the screening charge density at the gap interfaces are discussed in connection with plasmon ruler applications at subnanometric distances. PMID- 24216955 TI - Towards CMOS-compatible nanophotonics: ultra-compact modulators using alternative plasmonic materials. AB - We propose several planar layouts of ultra-compact plasmonic modulators that utilize alternative plasmonic materials such as transparent conducting oxides and titanium nitride. The modulation is achieved by tuning the carrier concentration in a transparent conducting oxide layer into and out of the plasmon resonance with an applied electric field. The resonance significantly increases the absorption coefficient of the modulator, which enables larger modulation depth. We show that an extinction ratio of 46 dB/um can be achieved, allowing for a 3-dB modulation depth in much less than one micron at the telecommunication wavelength. Our multilayer structures can be integrated with existing plasmonic and photonic waveguides as well as novel semiconductor-based hybrid photonic/electronic circuits. PMID- 24216956 TI - Gold nanoparticles for enhanced single molecule fluorescence analysis at micromolar concentration. AB - Individual metal nanoparticles represent an inexpensive and versatile platform to enhance the detection of fluorescent species at biologically relevant concentrations. Here we use fluorescence correlation spectroscopy to quantify the near-field detection volume and average fluorescence enhancement factors set by a single gold nanoparticle. We demonstrate detection volumes down to 270 zeptoliters (three orders of magnitude beyond the diffraction barrier) together with 60-fold enhancement of the fluorescence brightness per molecule. PMID- 24216957 TI - Blueshift of the surface plasmon resonance in silver nanoparticles: substrate effects. AB - We study the blueshift of the surface plasmon (SP) resonance energy of isolated Ag nanoparticles with decreasing particle diameter, which we recently measured using electron energy loss spectroscopy (EELS) [1]. As the particle diameter decreases from 26 down to 3.5 nm, a large blueshift of 0.5 eV of the SP resonance energy is observed. In this paper, we base our theoretical interpretation of our experimental findings on the nonlocal hydrodynamic model, and compare the effect of the substrate on the SP resonance energy to the approach of an effective homogeneous background permittivity. We derive the nonlocal polarizability of a small metal sphere embedded in a homogeneous dielectric environment, leading to the nonlocal generalization of the classical Clausius-Mossotti factor. We also present an exact formalism based on multipole expansions and scattering matrices to determine the optical response of a metal sphere on a dielectric substrate of finite thickness, taking into account retardation and nonlocal effects. We find that the substrate-based calculations show a similar-sized blueshift as calculations based on a sphere in a homogeneous environment, and that they both agree qualitatively with the EELS measurements. PMID- 24216958 TI - Mimicking electromagnetically induced transparency in the magneto-optical activity of magnetoplasmonic nanoresonators. AB - We show that the interaction between a plasmonic and a magnetoplasmonic metallic nanodisk leads to the appearance of magneto-optical activity in the purely plasmonic disk induced by the magnetoplasmonic one. Moreover, at specific wavelengths the interaction cancels the net electromagnetic field at the magnetoplasmonic component, strongly reducing the magneto-optical activity of the whole system. The MO activity has a characteristic Fano spectral shape, and the resulting MO inhibition constitutes the magneto-optical counterpart of the electromagnetic induced transparency. PMID- 24216959 TI - Efficient and intuitive method for the analysis of light scattering by a resonant nanostructure. AB - We present a semi-analytical formalism capable of handling the coupling of electromagnetic sources, such as point dipoles or free-propagating fields, with various kinds of dissipative resonances with radiation leakage, Ohmic losses or both. Due to its analyticity, the approach is very intuitive and physically sound. It is also very economic in computational resources, since once the resonances of a plasmonic or photonic resonator are known, their excitation coefficients are obtained analytically, independently of the polarization, frequency or location of the excitation source. To evidence that the present formalism is very general and versatile, we implement it with the commercial software COMSOL, rather than with our in-house numerical tools. PMID- 24216960 TI - Highly efficient broadband ultrafast plasmonics. AB - To date, considerable experimental and theoretical focus has been placed on the spatial control of Surface Plasmon Polaritons (SPPs) using nanostructured surfaces; however, research aimed toward accessing the ultrafast dynamics of SPPs remains vastly unexplored. Despite this, SPPs have the potential to exhibit some of the fastest possible optical processes, while maintaining the advantage of nanoscale spatial manipulation. Here, we present an experimental and computational investigation of a system that provides access to the efficient excitation of broadband, propagating SPP modes. To achieve this, a surface array of tailor designed, reduced symmetry nanostructures has been fabricated to enable the required control of the plasmon dispersion map to match sub 20 fs pulses in the near infra-red. Using a combination of optical spectroscopy and frequency resolved optical gating techniques, complimented by finite element computational analysis, the efficient excitation of propagating broadband plasmonic modes is demonstrated. PMID- 24216961 TI - Measurement of surface plasmon autocorrelation functions. AB - In this paper we demonstrate the realization of an autocorrelator for the characterization of ultrashort surface plasmon polariton (SPP) pulses. A wedge shaped structure is used to continuously increase the time delay between two interfering SPPs. The autocorrelation signal is monitored by non-linear two photon photoemission electron microscopy. The presented approach is applicable to other SPP sensitive detection schemes that provide only moderate spatial resolution and may therefore be of general interest in the field of ultrafast plasmonics. PMID- 24216962 TI - Mutual mode control of short- and long-range surface plasmons. AB - A symmetric metal slab waveguide simultaneously supports two opposite types of propagation mode similar to a metal film: short-range surface plasmon (SRSP) like mode and long-range surface plasmon (LRSP) like mode. The strong field confinement of SRSP-like mode plays a crucial role for nano-optical integrated circuits in spite of short propagation length. In order to avoid the trade-off between field confinement and propagation length, we demonstrate selective mode excitation and mutual mode conversion for nanofocusing mediated by LRSP-like mode. PMID- 24216963 TI - Surface lattice resonances strongly coupled to Rhodamine 6G excitons: tuning the plasmon-exciton-polariton mass and composition. AB - We demonstrate the strong coupling of surface lattice resonances (SLRs)- hybridized plasmonic/photonic modes in metallic nanoparticle arrays--to excitons in Rhodamine 6G molecules. We investigate experimentally angle-dependent extinction spectra of silver nanorod arrays with different lattice constants, with and without the Rhodamine 6G molecules. The properties of the coupled modes are elucidated with simple Hamiltonian models. At low momenta, plasmon-exciton polaritons--the mixed SLR/exciton states--behave as free-quasiparticles with an effective mass, lifetime, and composition tunable via the periodicity of the array. The results are relevant for the design of plasmonic systems aimed at reaching the quantum degeneracy threshold, wherein a single quantum state becomes macroscopically populated. PMID- 24216964 TI - Surface plasmon dispersion in metal hole array lasers. AB - We experimentally study surface plasmon lasing in a series of metal hole arrays on a gold-semiconductor interface. The sub-wavelength holes are arranged in square arrays of which we systematically vary the lattice constant and hole size. The semiconductor medium is optically pumped and operates at telecom wavelengths (lambda ~ 1.5 MUm). For all 9 studied arrays, we observe surface plasmon (SP) lasing close to normal incidence, where different lasers operate in different plasmonic bands and at different wavelengths. Angle- and frequency-resolved measurements of the spontaneous emission visualizes these bands over the relevant (omega, k||) range. The observed bands are accurately described by a simple coupled-wave model, which enables us to quantify the backwards and right-angle scattering of SPs at the holes in the metal film. PMID- 24216965 TI - Plasmonic metasurfaces for efficient phase control in reflection. AB - We numerically study the optical properties of metal-insulator-metal resonators and metasurfaces, emphasizing the presence of gap-surface plasmon (GSP) resonances and their connection to the optical response. In relation to birefringent metal-backed metasurfaces, we show how a combination of metal nanobrick and nanocross elements allows one to fully control the phase of reflected light for two orthogonal polarizations simultaneously. The approach is exemplified by the design of a gradient birefringent metasurface that reflects two orthogonal polarization states into +2 and -3 diffraction order, respectively, with a reflectivity up to ~ 80% and in a broad wavelength range around the design wavelength of 800 nm. Finally, we introduce the concept of metascatterers, which are wavelength-sized polarization-sensitive scatterers. PMID- 24216966 TI - The role of gap plasmons in light emission from tunnel junctions. AB - Light emission from the junction of a scanning tunneling microscope (STM) is examined in the presence of 20 nm topographical features in thin gold films. These features significantly modify the emission rates of the junction. Contributions to this modification are discriminated by examining emission rates on samples where the material is varied spatially. It is found that the variability in STM photoemission rates between a gold tip and a gold sample under ambient conditions is due to the modification of localized gap plasmon modes and not to the presence of an electroluminescent gold cluster on the STM probe apex. PMID- 24216967 TI - Plasmonic enhancement of the third order nonlinear optical phenomena: figures of merit. AB - Recent years have seen increased interest in the plasmonic enhancement of nonlinear optical effects, yet there remains an uncertainty as to the limits of this enhancement. We present a simple and physically transparent theory for the plasmonic enhancement of third order nonlinear optical processes and show that while a huge enhancement of the effective nonlinear index can be attained, the most relevant figure of merit, the phase shift per one absorption length, remains very low. This suggests that while nonlinear plasmonic materials are not suitable for applications requiring high efficiency, for example in all-optical switching and wavelength conversion, they can be very useful for applications where overall high efficiency is not critical, such as in sensing. PMID- 24216968 TI - Optical control of plasmonic fields by phase-modulated pulse excitations. AB - We developed an advanced near-field optical method by combining an ultrafast near field optical microscope with a prism-based pulse shaping system. We used this apparatus to visualize plasmonic optical fields and to measure the lifetime of plasmons excited on a rough gold film. We also studied the influence of the phase modulation of the excitation pulse on the spatial distribution of the optical fields. We found that the spatial distribution of the optical fields can be controlled by a negatively chirped pulse. PMID- 24216969 TI - Sensing properties of lattice resonances of 2D metal nanoparticle arrays: an analytical model. AB - Theoretical study of sensing properties of lattice resonances supported by arrays of gold nanoparticles expressed in terms of the figure of merit (FOM) is reported. Analytical expressions for the FOM for surface and bulk refractive index changes are derived to establish the relationship between the sensing performance and design parameters and to allow for the design of nanoparticle arrays with optimal sensing performance. It is demonstrated that lattice resonances exhibit about two orders of magnitude higher bulk FOM than localized surface plasmon (LSP) resonance and that the surface FOM provided by lattice resonances and LSP resonances are comparable. PMID- 24216970 TI - Tunable optical antennas enabled by the phase transition in vanadium dioxide. AB - Optical antennas, subwavelength metallic structures resonating at visible frequencies, are a relatively new branch of antenna technology being applied in science, technology and medicine. Dynamically tuning the resonances of these antennas would increase their range of application and offer potential increases in plasmonic device efficiencies. Silver nanoantenna arrays were fabricated on a thin film of the phase change material vanadium dioxide (VO(2)) and the resonant wavelength of these arrays was modulated by increasing the temperature of the substrate above the critical temperature (approximately 68 degrees C). Depending on the array, wavelength modulation of up to 110 nm was observed. PMID- 24216971 TI - Nonlocal propagation and tunnelling of surface plasmons in metallic hourglass waveguides. AB - The nanofocusing performance of hourglass plasmonic waveguides is studied analytically and numerically. Nonlocal effects in the linearly tapered metal-air metal stack that makes up the device are taken into account within a hydrodynamical approach. Using this hourglass waveguide as a model structure, we show that spatial dispersion drastically modifies the propagation of surface plasmons in metal voids, such as those generated between touching particles. Specifically, we investigate how nonlocal corrections limit the enormous field enhancements predicted by local electromagnetic treatments of geometric singularities. Finally, our results also indicate the emergence of nonlocality assisted tunnelling of plasmonic modes across hourglass contacts as thick as 0.5 nm. PMID- 24216972 TI - Severe axial myopathy in McArdle disease. AB - IMPORTANCE: McArdle disease is a nonlysosomal glycogenosis that classically manifests with exercise-induced pain from childhood. Fixed weakness may occur from the fifth decade and is typically mild and located around the shoulder girdle. OBSERVATIONS: We describe a 61-year-old man with exercise-induced pain from a young age and a 3-year history of weight loss and an elevated creatine kinase level up to 4000 U/L. On examination, he was severely atrophic and weak in his shoulder girdle and the entire paraspinal musculature. Magnetic resonance imaging confirmed that the paraspinal musculature was completely converted to fat. A muscle biopsy specimen was myopathic with a lack of myophosphorylase and multiple large vacuoles with glycogen. A nonischemic forearm test demonstrated a lack of increase in lactate together with an exaggerated ammonium elevation. Genetic testing verified the suspicion of McArdle disease. CONCLUSIONS AND RELEVANCE: This is a highly atypical presentation of McArdle disease with severe paraspinal wasting and weakness. We suspect that this is related to the unusual amount of glycogen vacuoles and stress the importance of including McArdle disease in the differential diagnosis of axial myopathy. PMID- 24216973 TI - Multiple myeloma: relationship to antioxidant esterases. AB - OBJECTIVE: To investigate the status of the oxidant/antioxidant balance in patients with multiple myeloma compared to healthy controls. MATERIALS AND METHODS: This study was conducted on 40 multiple myeloma patients and 40 healthy controls of matched age and sex. Serum total thiol, oxidative stress index (OSI), total oxidant status (TOS), and total antioxidant status (TAS) were measured using colourimetric methods; paraoxonase-1 and arylesterase enzyme activities were also quantified. RESULTS: Serum paraoxonase-1 and arylesterase activities and total thiol levels were significantly lower (p = 0.0001, p = 0.036 and p < 0.0001, respectively), whereas TOS and OSI levels were significantly higher (p < 0.0001 for both parameters) in multiple myeloma patients compared to controls. However, no significant differences in TAS were identified when the two groups were compared. CONCLUSIONS: Our findings indicate an impaired oxidative/antioxidative balance in multiple myeloma. We recommend further studies with larger groups to investigate the possible relationship between oxidative stress and the aetiopathogenesis of multiple myeloma. PMID- 24216974 TI - Effects of central and peripheral administration of neuropeptide s on the level of serum proinflammatory cytokines in pigs. AB - OBJECTIVES: The recently discovered neuropeptide S (NPS) and its cognate receptor represent a novel system of neuromodulation and are involved in many physiological and pathological processes. NPS has been implicated in the regulation of proinflammatory cytokine secretion in the pulmonary alveolar macrophages (PAMs) of pigs in vitro. In this study, we tested the hypothesis whether either central or peripheral injection of NPS would stimulate the secretion of the proinflammatory cytokines in pigs. METHODS: In experiment 1, pigs were fitted with an intracerebroventricular cannula and indwelling jugular catheters, and were then randomly assigned to receive 10 or 30 nmol NPS in artificial cerebrospinal fluid. In experiment 2, pigs were fitted with indwelling jugular catheters, and randomly received 15 or 30 nmol NPS in saline. Serial blood samples were collected every 10 min for 1 h before and for 2 h after injections, and serum concentrations of IL-1beta, IL-6 and TNF-alpha were determined. RESULTS: Serum concentrations of these cytokines were increased in pigs that received central and peripheral injection of NPS, and the elevated secretion of these cytokines was in a time- and concentration-dependent manner. CONCLUSION: The level of serum proinflammatory cytokines could be activated by both central and peripheral administration of NPS in a dose- and time-dependent manner in the pig. The present data support the concept that NPS may be considered as a potent modulator for the immune system and may play an important role in the inflammation and immune system of pigs. PMID- 24216975 TI - Enhanced methanol oxidation and oxygen reduction reactions on palladium-decorated FeCo@Fe/C core-shell nanocatalysts in alkaline medium. AB - Palladium based nano-alloys are well known for their unique electrocatalytic properties. In this work, a palladium-decorated FeCo@Fe/C core-shell nanocatalyst has been prepared by a new method called microwave-induced top-down nanostructuring and decoration (MITNAD). This simple, yet efficient technique, resulted in the generation of sub-10 nm sized FeCo@Fe@Pd nanocatalysts (mainly 3 5 nm) from a micron-sized (0.21-1.5 MUm) FeCo@Fe/C. The electrocatalytic activities of the core-shell nanocatalysts were explored for methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR) in alkaline medium. A negative shift of 300 mV in the onset potential for MOR was observed, with a current thrice that of the Pd/C catalysts. A very low resistance to electron transfer (Rct) was observed while the ratio of forward-to-backward oxidation current (If/Ib) was doubled. The overpotential of ORR was significantly reduced with a positive shift of about 250 mV and twice the reduction current density was observed in comparison with Pd/C nanocatalysts with the same mass loading. The kinetic parameters (in terms of the Tafel slope (b) = -59.7 mV dec(-1) (Temkin isotherm) and high exchange current density (jo) = 1.26 * 10(-2) mA cm(-2)) provide insights into the favorable electrocatalytic performance of the catalysts in ORR in alkaline media. Importantly, the core-shell nanocatalyst exhibited excellent resistance to possible methanol cross-over during ORR, which shows excellent promise for application in direct alkaline alcohol fuel cells (DAAFCs). PMID- 24216976 TI - Deep brain stimulation for obsessive-compulsive disorder: is the side relevant? AB - BACKGROUND: Deep brain stimulation for obsessive-compulsive disorder (OCD) has targeted several subcortical nuclei, including the subthalamic nucleus (STN) and the nucleus accumbens. While the most appropriate target is still being looked for, little attention has been given to the side of the stimulated hemisphere in relationship to outcome. METHODS: We report 2 patients diagnosed with OCD, one having symmetry obsessions and the other one with sexual-religious obsessive thoughts. They were implanted bilaterally with deep electrodes located at both STN and nuclei accumbens. The effectiveness of the stimulation was tested for every possible paired combination of electrodes guided by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction. RESULTS: In both cases, the combination of electrodes which best relieved the OCD symptoms was both the left STN and left accumbens. In case 1, the preoperative Y-BOCS score was 33, and 1 month after stimulation it was 16. In case 2, the Y-BOCS scores were 33 and 3, respectively, with the patient being free of obsessions. CONCLUSION: Some reports suggest that lesion stimulation or stimulation of only the right side relieves OCD symptoms. However, anatomical and functional studies are not conclusive as to which side is most affected in OCD. Possibly, each OCD patient has an individualized optimal side to stimulate. PMID- 24216977 TI - Hearing loss is part of the clinical picture of ENPP1 loss of function mutation. AB - BACKGROUND: Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of function mutations have been described in patients with autosomal recessive hypophosphatemic rickets (HR), in patients with generalized arterial calcification of infancy (GACI) and in several patients with both conditions. Out of more than 50 cases of homozygous or compound heterozygous ENPP1 loss-of function mutations published so far, 1 case with labyrinthine deafness probably due to occlusion of inner ear supplying arteries and 2 cases of conductive hearing loss due to stapedovestibular calcification diagnosed in childhood have been reported. AIMS: To report a case of ENPP1 loss-of-function novel mutation presenting with HR and very early onset and severe hearing loss. METHODS: Case report and review of the literature. RESULTS: We report on a patient homozygous for a novel 1-bp deletion in ENPP1 that presented with GACI evolving towards HR associated with a mixed hearing loss (both labyrinthine and conductive) diagnosed at 9 days of life that evolved towards profound labyrinthine deafness. CONCLUSION: Hearing loss is a rare finding in patients with ENPP1 loss-of function mutations. Interestingly, it has already been described in other affected patients, in ENPP1 knock-out mice and in other diseases of pyrophosphate metabolism. Conversely it seems to be absent in children with the X-linked form of HR. PMID- 24216978 TI - Changes in body composition in patients with chronic obstructive pulmonary disease: do they influence patient-related outcomes? AB - AIMS: The follow-up of the ECLIPSE study, a prospective longitudinal study to identify and define parameters that predict disease progression over 3 years in chronic obstructive pulmonary disease (COPD), allows the examination of the effect of body composition changes on COPD-related outcomes. METHODS: Body composition and health status were established in 2,115 COPD patients, 327 smoking and 239 nonsmoking controls at baseline and 3 years, while mortality was recorded in year 2 and 3 in the COPD patients. Associations between fat free mass index (FFMI) and fat mass index (FMI) changes to deterioration in health status and mortality were determined. RESULTS: Change in FFMI and FMI over 3 years was small and comparable between the groups. Underweight and obese patients had the worst health status. Worsening health status was associated with FFMI decrease in underweight patients and FMI increase in overweight/obese patients. While overweight patients had the lowest mortality, FFMI or FMI decrease was associated with a higher mortality. CONCLUSION: Changes in body composition over 3 years were small and comparable in COPD patients and control subjects. Nevertheless, muscle mass decline in underweight and fat mass increase in overweight/obese patients is associated with worsening health status. Overweight is associated with decreased mortality, but muscle mass and fat mass decline are detrimental for mortality. PMID- 24216979 TI - Hypoxia-inducible factors: mediators of cancer progression; prognostic and therapeutic targets in soft tissue sarcomas. AB - Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression. PMID- 24216980 TI - Global Decrease of Histone H3K27 Acetylation in ZEB1-Induced Epithelial to Mesenchymal Transition in Lung Cancer Cells. AB - The epithelial to mesenchymal transition (EMT) enables epithelial cells with a migratory mesenchymal phenotype. It is activated in cancer cells and is involved in invasion, metastasis and stem-like properties. ZEB1, an E-box binding transcription factor, is a major suppressor of epithelial genes in lung cancer. In the present study, we show that in H358 non-small cell lung cancer cells, ZEB1 downregulates EpCAM (coding for an epithelial cell adhesion molecule), ESRP1 (epithelial splicing regulatory protein), ST14 (a membrane associated serine protease involved in HGF processing) and RAB25 (a small G-protein) by direct binding to these genes. Following ZEB1 induction, acetylation of histone H4 and histone H3 on lysine 9 (H3K9) and 27 (H3K27) was decreased on ZEB1 binding sites on these genes as demonstrated by chromatin immunoprecipitation. Of note, decreased H3K27 acetylation could be also detected by western blot and immunocytochemistry in ZEB1 induced cells. In lung cancers, H3K27 acetylation level was higher in the tumor compartment than in the corresponding stroma where ZEB1 was more often expressed. Since HDAC and DNA methylation inhibitors increased expression of ZEB1 target genes, targeting these epigenetic modifications would be expected to reduce metastasis. PMID- 24216981 TI - Glioma surgical aspirate: a viable source of tumor tissue for experimental research. AB - Brain cancer research has been hampered by a paucity of viable clinical tissue of sufficient quality and quantity for experimental research. This has driven researchers to rely heavily on long term cultured cells which no longer represent the cancers from which they were derived. Resection of brain tumors, particularly at the interface between normal and tumorigenic tissue, can be carried out using an ultrasonic surgical aspirator (CUSA) that deposits liquid (blood and irrigation fluid) and resected tissue into a sterile bottle for disposal. To determine the utility of CUSA-derived glioma tissue for experimental research, we collected 48 CUSA specimen bottles from glioma patients and analyzed both the solid tissue fragments and dissociated tumor cells suspended in the liquid waste fraction. We investigated if these fractions would be useful for analyzing tumor heterogeneity, using IHC and multi-parameter flow cytometry; we also assessed culture generation and orthotopic xenograft potential. Both cell sources proved to be an abundant, highly viable source of live tumor cells for cytometric analysis, animal studies and in-vitro studies. Our findings demonstrate that CUSA tissue represents an abundant viable source to conduct experimental research and to carry out diagnostic analyses by flow cytometry or other molecular diagnostic procedures. PMID- 24216983 TI - Ex vivo behaviour of human bone tumor endothelial cells. AB - Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31+ subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas. PMID- 24216982 TI - Protein kinase C epsilon and genetic networks in osteosarcoma metastasis. AB - Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCepsilon-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCepsilon transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCepsilon was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation. PMID- 24216984 TI - A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma. AB - mTOR inhibitors are emerging as important anti-neoplastic agents with a wide range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug, with a broad spectrum of anticancer activities. mTOR appears to enhance cancer cell survival following DNA damage, thus the inhibition of mTOR after irinotecan could theoretically show synergistic activities in patients. Both mTOR inhibitors and irinotecan have been used as single agents in soft tissue sarcomas with limited efficacy. We completed a phase I trial of the combination of the mTOR inhibitor, temsirolimus, and irinotecan in patients with advanced soft tissue sarcoma. Seventeen patients were recruited. The Phase II recommended dose is 20 mg of temsirolimus and 80 mg/m2 of irinotecan administered on weekly basis for three out of four weeks. Most frequently encountered toxicities include cytopenias, fatigue, and gastrointestinal toxicities. Two patients (one with leiomyosarcoma and one with high grade undifferentiated sarcoma) had stable disease for more than 12 months. PMID- 24216985 TI - Epigenetic modulating agents as a new therapeutic approach in multiple myeloma. AB - Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment. PMID- 24216987 TI - Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data. AB - Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis. PMID- 24216988 TI - The lack of predictors for rapid progression in prostate cancer patients receiving sipuleucel-T. AB - Sipuleucel-T is an immunotherapy indicated for the treatment of metastatic prostate cancer. It offers a new mechanism to treat prostate cancer without the side effects of hormone therapies and chemotherapies. In previous studies sipuleucel-T did not delay disease progression, but demonstrated an overall survival benefit compared to placebo. While clinical trials have evaluated the effects of sipuleucel-T on overall survival and progression, more studies are needed to evaluate its effectiveness and role in the management of prostate cancer. The objective of this study is to identify the incidence and possible predictors for disease progression in patients receiving sipuleucel-T. A retrospective review of patients who received sipuleucel-T between 1 September 2010 and 11 October 2011 was conducted (n = 36). Patients who changed therapy or died within 120 days were classified as experiencing rapid progression. Potential predictors of rapid progression were examined using logistic regression. Seven patients met criteria for rapid progression. Progression occurred in 72.2% of all patients. The median days to progression was 158. No significant predictors of rapid progression were identified. Currently no predictors have been found to be associated with rapid progression in prostate cancer patients on sipuleucel-T. PMID- 24216986 TI - Regulatory Roles for Long ncRNA and mRNA. AB - Recent advances in high-throughput sequencing technology have identified the transcription of a much larger portion of the genome than previously anticipated. Especially in the context of cancer it has become clear that aberrant transcription of both protein-coding and long non-coding RNAs (lncRNAs) are frequent events. The current dogma of RNA function describes mRNA to be responsible for the synthesis of proteins, whereas non-coding RNA can have regulatory or epigenetic functions. However, this distinction between protein coding and regulatory ability of transcripts may not be that strict. Here, we review the increasing body of evidence for the existence of multifunctional RNAs that have both protein-coding and trans-regulatory roles. Moreover, we demonstrate that coding transcripts bind to components of the Polycomb Repressor Complex 2 (PRC2) with similar affinities as non-coding transcripts, revealing potential epigenetic regulation by mRNAs. We hypothesize that studies on the regulatory ability of disease-associated mRNAs will form an important new field of research. PMID- 24216989 TI - Lost in translation: ambiguity in nerve sheath tumor nomenclature and its resultant treatment effect. AB - There is much ambiguity surrounding the diagnosis of nerve sheath tumors, including atypical neurofibroma and low-grade MPNST, and yet, the distinction between these entities designates either benign or malignant behavior and thus carries presumed profound prognostic importance that often guides treatment. This study reviews the diagnostic criteria used to designate atypical neurofibroma from low-grade MPNSTs and reviews existing literature the natural history of each of these tumors to see if the distinction is, in fact, of importance. PMID- 24216990 TI - Novel systemic therapies in advanced liposarcoma: a review of recent clinical trial results. AB - Liposarcoma is one of the most common adult soft tissue sarcomas and consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are currently limited. In the past decade, a better understanding of the distinct genetic and molecular aberrations for each of the three histologic subtypes has led to the development of several novel systemic therapies. Data from phase I and early phase II clinical trials have been reported. Despite challenges with conducting clinical trials in liposarcoma, preliminary results for several of these novel, biology-driven therapies are encouraging. PMID- 24216991 TI - 99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies. AB - Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1-2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99mTc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1-4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome based medicine, applicable to all cancer patients. PMID- 24216992 TI - Immunotherapy and immune evasion in prostate cancer. AB - Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies. PMID- 24216993 TI - Current therapeutic strategies and novel approaches in osteosarcoma. AB - Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies. PMID- 24216994 TI - Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells. AB - Osteopontin and MMP9 are implicated in angiogenesis and cancer progression. The objective of this study is to gain insight into the molecular mechanisms underlying angiogenesis, and to elucidate the role of osteopontin in this process. We report here that osteopontin/alphavbeta3 signaling pathway which involves ERK1/2 phosphorylation regulates the expression of VEGF. An inhibitor to MEK or curcumin significantly suppressed the phosphorylation of ERK1/2 and expression of VEGF. MMP9 knockdown reduces the secretion but not the expression of VEGF. Moreover, MMP9 knockdown increases the release of angiostatin, a key protein that suppresses angiogenesis. Conditioned media from PC3 cells treated with curcumin or MEK inhibitor inhibited tube formation in vitro in human microvascular endothelial cells. Similar inhibitory effect on tube formation was found with conditioned media collected from PC3 cells expressing mutant osteopontin at integrin-binding site and knockdown of osteopontin or MMP9. We conclude that MMP9 activation is associated with angiogenesis via regulation of secretion of VEGF and angiostatin in PC3 cells. Curcumin is thus a potential drug for cancer treatment because it demonstrated anti-angiogenic and anti-invasive properties. PMID- 24216995 TI - Ras and rheb signaling in survival and cell death. AB - One of the most obvious hallmarks of cancer is uncontrolled proliferation of cells partly due to independence of growth factor supply. A major component of mitogenic signaling is Ras, a small GTPase. It was the first identified human protooncogene and is known since more than three decades to promote cellular proliferation and growth. Ras was shown to support growth factor-independent survival during development and to protect from chemical or mechanical lesion induced neuronal degeneration in postmitotic neurons. In contrast, for specific patho-physiological cases and cellular systems it has been shown that Ras may also promote cell death. Proteins from the Ras association family (Rassf, especially Rassf1 and Rassf5) are tumor suppressors that are activated by Ras GTP, triggering apoptosis via e.g., activation of mammalian sterile 20-like (MST1) kinase. In contrast to Ras, their expression is suppressed in many types of tumours, which makes Rassf proteins an exciting model for understanding the divergent effects of Ras activity. It seems likely that the outcome of Ras signaling depends on the balance between the activation of its various downstream effectors, thus determining cellular fate towards either proliferation or apoptosis. Ras homologue enriched in brain (Rheb) is a protein from the Ras superfamily that is also known to promote proliferation, growth, and regeneration through the mammalian target of rapamycin (mTor) pathway. However, recent evidences indicate that the Rheb-mTor pathway may switch its function from a pro growth into a cell death pathway, depending on the cellular situation. In contrast to Ras signaling, for Rheb, the cellular context is likely to modulate the whole Rheb-mTor pathway towards cellular death or survival, respectively. PMID- 24216996 TI - Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse. AB - Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIalpha inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIalpha inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness. PMID- 24216998 TI - Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin's Lymphoma. AB - In classical Hodgkin's lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques at the single cell level has substantially improved our understanding of the molecular pathogenesis of HL. Gene expression profiling, comparative genomic hybridization analysis, micro-RNA expression profiling and viral oncogene sequencing have deepened our knowledge of numerous facets of H- and RS-cell gene expression deregulation. The question remains whether disturbed signaling pathways and deregulated transcription factors are at the origin of refractory/relapsing Hodgkin's lymphoma or whether these hallmarks are at least partially related to another major factor. We recently showed that the 3D nuclear organization of telomeres and chromosomes marked the transition from H- to RS-cells in HL cell lines. This transition is associated with progression of telomere dysfunction, shelterin disruption and progression of complex chromosomal rearrangements. We reported analogous findings in refractory/relapsing HL and identified the shelterin proteins TRF1, TRF2 and POT1 as targets of the LMP1 oncogene in post-germinal center B-cells. Here we summarize our findings, including data not previously published, and propose a model in which progressive disruption of nuclear integrity, a form of genomic instability, is the key-player in refractory/relapsing HL. Therapeutic approaches should take these findings into account. PMID- 24217000 TI - NMR spectroscopy for thin films by magnetic resonance force microscopy. AB - Nuclear magnetic resonance (NMR) is a fundamental research tool that is widely used in many fields. Despite its powerful applications, unfortunately the low sensitivity of conventional NMR makes it difficult to study thin film or nano sized samples. In this work, we report the first NMR spectrum obtained from general thin films by using magnetic resonance force microscopy (MRFM). To minimize the amount of imaging information inevitably mixed into the signal when a gradient field is used, we adopted a large magnet with a flat end with a diameter of 336 MUm that generates a homogeneous field on the sample plane and a field gradient in a direction perpendicular to the plane. Cyclic adiabatic inversion was used in conjunction with periodic phase inversion of the frequency shift to maximize the SNR. In this way, we obtained the (19)F NMR spectrum for a 34 nm-thick CaF2 thin film. PMID- 24216999 TI - Effects of ellagic Acid on angiogenic factors in prostate cancer cells. AB - BACKGROUND: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor (VEGF) and heme oxygenase system (HO) have emerged as important modulators of tumor growth and metastasis. METHODS: The anti angiogenic effects of EA were investigated in the human prostatic cancer cell line LnCap. HO-1, HO-2, CYP2J2 and soluble epoxyde hydrolase (sEH) expressions were evaluated by western blotting. Levels of VEGF and osteoprotegerin (OPG) were determined in the culture supernatant using an ELISA assay, while CYP mRNAs were determined by qRT-PCR. RESULTS: EA treatment induced a significant decrease (p < 0.05) in HO-1, HO-2 and CYP2J2 expression, and in VEGF and OPG levels. Similarly CYP2J2, CYP4F2 and CYPA22 mRNAs were significantly (p < 0.05) down-regulated by EA treatment. The decrease in CYP2J2 mRNA was associated with an increase in sEH expression. CONCLUSIONS: RESULTS reported in the present study highlighted the ability of EA to modulate a new pathway, in addition to anti-proliferative and pro-differentiation properties, via a mechanism that involves a decrease in eicosanoid synthesis and a down-regulation of the HO system in prostate cancer. PMID- 24217002 TI - Overhead lift systems reduce back injuries among burn care providers. AB - Extensive patient handling in burn care provides ample opportunities for staff injury. The objective of this retrospective study was to evaluate frequency of work-related back injury pre- and postinstallation of overhead lifting systems (OLS) in a burn intensive care unit. After receiving institutional review board approval, the Workers Compensation Fund of Utah released deidentified back injury claims filed from the authors' burn center between January 1, 2001 and December 31, 2012. Number of back injuries, cost to workers' compensation, and missed workdays were examined. Three distinct time periods were analyzed based on the timing of installation of OLS in the burn center. Forty-five workers were injured in the burn unit; most were female (76%) nurses (73%), with the majority having lower-back injury (71%). Thirty claims (67%) involved staff with a previous back injury. Median age was 32 years (interquartile range, 22-40) and median term of employment at the burn center before injury was 3.7 years (interquartile range, 1.6-7.7). During the intervention period, rate of staff injuries, number of missed workdays, and total number of paid claims decreased significantly. In the period since installation, only one claim has been filed, which is the lowest number of claims that any individual intensive care unit has reported in the facility. The burn unit installed five OLS at a cost of $7000 per unit. This retrospective review indicated that the installation of OLS on the burn unit was an effective tool for reducing staff injury and associated costs. Back injury was essentially eliminated when five OLS were installed. PMID- 24216997 TI - Epigenetics and colorectal cancer pathogenesis. AB - Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy. PMID- 24217003 TI - Machine learning source separation using maximum a posteriori nonnegative matrix factorization. AB - A novel unsupervised machine learning algorithm for single channel source separation is presented. The proposed method is based on nonnegative matrix factorization, which is optimized under the framework of maximum a posteriori probability and Itakura-Saito divergence. The method enables a generalized criterion for variable sparseness to be imposed onto the solution and prior information to be explicitly incorporated through the basis vectors. In addition, the method is scale invariant where both low and high energy components of a signal are treated with equal importance. The proposed algorithm is a more complete and efficient approach for matrix factorization of signals that exhibit temporal dependency of the frequency patterns. Experimental tests have been conducted and compared with other algorithms to verify the efficiency of the proposed method. PMID- 24217004 TI - A step toward polytwistane: synthesis and characterization of C2-symmetric tritwistane. AB - Twistane is a classic hydrocarbon with fascinating stereochemical properties. Herein we describe a series of oligomers of twistane that converges on a chiral nanorod, which we term polytwistane. A member of this series, C2-symmetric tritwistane, has been synthesized for the first time. PMID- 24217005 TI - Structural properties of the inner coordination sphere of indium chloride complexes in organic and aqueous solutions. AB - The nature of the inner coordination sphere of In(3+) present in both the organic and aqueous solutions during the solvent extraction of In(3+) from an aqueous HCl solution with tri-n-octyl amine (TOA) was investigated by In K-edge XAFS. This information was then used to clarify the details of the extraction properties of indium chloride anion complexes with TOA. In aqueous HCl solution (0.1-10 M), In(3+) exists as octahedral anion complexes, [InCln(H2O)6-n](3-n) (n >= 4); the [InCl6](3-) complex is dominant at 10 M HCl. The extraction of In(3+) from HCl solution with TOA was performed using two kinds of diluents: nitrobenzene (NB) or n-dodecane (DD), which contained 20 vol% of 2-ethylhexanol as an additive. The stoichiometric composition of the extracted complexes, which is estimated from the distribution ratios of In(3+), is affected by the diluents and the HCl concentration of the aqueous phase; the apparent values of TOA/In(3+) in the extracted complex are 3 for DD-1 M HCl (diluent-aqueous phase) and DD-5 M HCl, 2 for NB-1 M HCl and NB-5 M HCl, and 1 for NB-10 M HCl. The EXAFS analysis of these extracted complexes shows that the In(3+) has ~4 Cl(-) at ~2.336 A and no H2O in the inner coordination sphere; additionally, the shape of the XANES suggests that their coordination geometry is tetrahedral. Therefore, the same tetrahedral [InCl4](-) complex is formed during the extraction in spite of the variation in the stoichiometric composition (TOA/In(3+) = 1-3) of the extracted complexes. PMID- 24217007 TI - Lack of association between lactotransferrin polymorphism and dental caries. AB - OBJECTIVE: Dental caries is a complex, multifactorial disease and one of the most common illnesses worldwide. Its etiology is related to microbial, dietary and host factors. Recent evidence suggests a role of lactotransferrin (LTF) in caries. The purpose of this study was to determine the association between LTF gene polymorphism and dental caries. METHODS: In this case-control study, 637 unrelated children, aged 11-13 years, were enrolled. The subjects were divided into two groups, i.e. caries-free (decayed/missing/filled teeth = 0) and caries affected children (decayed/missing/filled teeth >= 1). The LTF rs1126478 (140A/G in exon 2, Lys/Arg) genotypes were determined by PCR with restriction analysis using the EarI enzyme. RESULTS: Of 637 children, 155 (24.3%) were caries free. There were no statistically significant differences between caries levels and allele or genotype distributions in the total cohort. When the caries-affected group (n = 482) was stratified into low (decayed/missing/filled teeth = 1), moderate (2 <= decayed/missing/filled teeth <= 3) and high (decayed/missing/filled teeth >= 4) caries experience, allele and genotype frequencies were similar among all subgroups. CONCLUSIONS: The LTF 140A/G (exon 2, Lys/Arg) polymorphism was not associated with the susceptibility to or severity of dental caries in the Czech population. PMID- 24217008 TI - Medical image registration by combining global and local information: a chain type diffeomorphic demons algorithm. AB - The demons algorithm is a popular algorithm for non-rigid image registration because of its computational efficiency and simple implementation. The deformation forces of the classic demons algorithm were derived from image gradients by considering the deformation to decrease the intensity dissimilarity between images. However, the methods using the difference of image intensity for medical image registration are easily affected by image artifacts, such as image noise, non-uniform imaging and partial volume effects. The gradient magnitude image is constructed from the local information of an image, so the difference in a gradient magnitude image can be regarded as more reliable and robust for these artifacts. Then, registering medical images by considering the differences in both image intensity and gradient magnitude is a straightforward selection. In this paper, based on a diffeomorphic demons algorithm, we propose a chain-type diffeomorphic demons algorithm by combining the differences in both image intensity and gradient magnitude for medical image registration. Previous work had shown that the classic demons algorithm can be considered as an approximation of a second order gradient descent on the sum of the squared intensity differences. By optimizing the new dissimilarity criteria, we also present a set of new demons forces which were derived from the gradients of the image and gradient magnitude image. We show that, in controlled experiments, this advantage is confirmed, and yields a fast convergence. PMID- 24217009 TI - Perinatal and short-term neonatal outcomes of posterior fossa anomalies. AB - OBJECTIVE: To describe the perinatal and neonatal outcomes for fetuses with posterior fossa (PF) anomalies - mega-cisterna magna (MCM), persistent Blake's pouch (PBP) or the Dandy-Walker continuum (DWC) - using a new classification. METHODS: 46 cases with PF anomaly diagnosed on ultrasound (US) between 16 and 28 weeks' gestation were included. The images were reviewed and classified as one of the following: MCM, PBP or DWC. Outcomes were obtained from patient records. RESULTS: 30 cases with DWC, 6 with MCM, and 10 with PBP were identified. Associated anomalies were present in all groups, but more frequent in DWC. Agenesis of the corpus callosum and ventriculomegaly were more common in DWC than in MCM or PBP. Only fetuses with DWC were found to have chromosomal abnormalities. Perinatal outcomes differed significantly, with terminations of pregnancy more frequent in DWC. In the immediate postnatal period, infants with DWC had worse outcomes than those with MCM and PBP. Across all groups, those with associated anomalies had worse outcomes than those with an isolated PF anomaly. CONCLUSION: Infants antenatally diagnosed with DWC had worse perinatal and short term neonatal outcomes than those with MCM or PBP. Those with associated anomalies had uniformly poorer outcomes than those with isolated anomalies. PMID- 24217010 TI - Properly selected skin cancer treatments are very effective. PMID- 24217011 TI - Merkel cell polyomavirus-positive Merkel cell carcinoma requires viral small T antigen for cell proliferation. PMID- 24217012 TI - Response to Shuda et al. PMID- 24217013 TI - Response to Rogers et al. PMID- 24217014 TI - Polymorphisms in IL-1B distinguish between psoriasis of early and late onset. PMID- 24217015 TI - Effect of exposure to diazinon on adult rat's brain. AB - Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain. PMID- 24217016 TI - Enhanced hydrogen sensing properties of graphene by introducing a mono-atom vacancy. AB - To facilitate the dissociative adsorption of H2 molecules on pristine graphene, the addition of a mono-atom-vacancy to graphene is proposed. This leads to reduction of the dissociative energy barrier for a H2 molecule on graphene from 3.097 to 0.805 eV for the first H2 and 0.869 eV for the second, according to first principles calculations. As a result, two H2 molecules can be easily dissociatively adsorbed on this defected graphene at room temperature. The electronic structure and conductivity of the graphene change significantly after H2 adsorption. In addition, the related dissociative adsorption phase diagrams under different temperatures and partial pressures show that this dissociative adsorption at room temperature is very sensitive (10(-35) mol L(-1)). Therefore, this defected graphene is promising for ultra-sensitive room temperature hydrogen sensing. PMID- 24217017 TI - Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. AB - IMPORTANCE: Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation. OBSERVATIONS: Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy. CONCLUSIONS AND RELEVANCE: The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies. PMID- 24217018 TI - Assessment of the severity of acute pulmonary embolism using CT pulmonary angiography parameters. AB - AIM: To evaluate the association between computed tomography parameters and clinical signs in patients with acute pulmonary embolism. METHODS: 109 patients retrospectivelly selected from hospital database with acute pulmonary embolism verified by CT pulmonary angiography. The following parameters were assessed: pulmonary artery diameter to aorta diameter ratio (PA/Ao), normalized pulmonary artery diameter (nPA), right ventricular to left ventricular diameter ratio from CT (RV CT/LV CT), normalized end-diastolic right ventricular diameter (nRVD echo) and right to left ventricular end diastolic diameter ratio (RV echo/LV echo) from echocardiography. RESULTS: Multivariate regression analysis showed a significant association between PA/Ao and thrombolysed (0.99) to non-thrombolysed (0.90) patients, OR=1.56 P=0.012, and also RV CT/LV CT and thrombolysed 1.5 to non thrombolysed (0.94) patients OR=1.24 P=0.002. The significant difference was also found in intensive care unit hospitalization necessity (ICU-Y/N) and RV CT/LV CT ratio (ICU-Y 1.42, ICU-N 0.91) OR=1.26 P=0.003, and RV echo/LV echo (ICU-Y 0.82, ICU-N 0.65) OR=1.83 P=0.033. CONCLUSION: From the CT pulmonary angiography parameters, the RV CT/LV CT showed a significant association with both thrombolysis administration and ICU hospitalization. The PA/Ao had relation only to thrombolytic therapy as well as RV echo/LV echo only to ICU hospitalization. PMID- 24217019 TI - Cutaneous silent periods in multiple system atrophy. AB - AIM: The cutaneous silent period (CSP) is a spinal inhibitory reflex primarily mediated by A-delta fibers. Prolonged CSPs have been reported in patients with restless legs syndrome (RLS) and idiopathic Parkinson's disease (IPD). Dopaminergic medication normalizes the CSP, concurring with the effect of levodopa on CSPs. To date, CSPs have not been extensively studied in patients with multiple system atrophy (MSA). The purpose of this study was to confirm abnormal CSP findings in a group of MSA patients and to affirm the lack of influence of levodopa on CSPs during long-term treatment. METHODS: We investigated 15 patients (4 males, 11 females, age 58-71 years) who fulfilled the diagnostic criteria for possible MSA. Thirteen patients had predominant parkinsonian symptoms (MSA-P), 2 had predominant cerebellar signs (MSA-C). We recorded CSPs in thenar muscles following noxious digit II stimulation. Sixteen healthy volunteers (6 males, 10 females, range 24-56 years) served as control subjects for CSP recordings. RESULTS: Group average CSP onset was mildly delayed (P<0.01), whereas CSP end latency (P<0.001) were markedly delayed and CSP duration prolonged (P<0.001) in MSA patients compared to healthy controls. MSA patients on levodopa treatment did not differ in their CSPs from those without levodopa. The dose of levodopa did not correlate to any CSP parameter. CONCLUSION: The observed CSP prolongation corroborates previous findings in a limited number of MSA patients. The ineffectiveness of long-term levodopa on CSP abnormalities is consistent with its poor clinical effect in MSA. PMID- 24217020 TI - Construction and application of a protein interaction map for white spot syndrome virus (WSSV). AB - White spot syndrome virus (WSSV) is currently the most serious global threat for cultured shrimp production. Although its large, double-stranded DNA genome has been completely characterized, most putative protein functions remain obscure. To provide more informative knowledge about this virus, a proteomic-scale network of WSSV-WSSV protein interactions was carried out using a comprehensive yeast two hybrid analysis. An array of yeast transformants containing each WSSV open reading frame fused with GAL4 DNA binding domain and GAL4 activation domain was constructed yielding 187 bait and 182 prey constructs, respectively. On screening of ~28,000 pairwise combinations, 710 interactions were obtained from 143 baits. An independent coimmunoprecipitation assay (co-IP) was performed to validate the selected protein interaction pairs identified from the yeast two-hybrid approach. The program Cytoscape was employed to create a WSSV protein-protein interaction (PPI) network. The topology of the WSSV PPI network was based on the Barabasi Albert model and consisted of a scale-free network that resembled other established viral protein interaction networks. Using the RNA interference approach, knocking down either of two candidate hub proteins gave shrimp more protection against WSSV than knocking down a nonhub gene. The WSSV protein interaction map established in this study provides novel guidance for further studies on shrimp viral pathogenesis, host-viral protein interaction and potential targets for therapeutic and preventative antiviral strategies in shrimp aquaculture. PMID- 24217021 TI - Label-free quantitative protein profiling of vastus lateralis muscle during human aging. AB - Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers. PMID- 24217024 TI - Comparative chromosomal mapping of microsatellites in Leporinus species (Characiformes, Anostomidae): unequal accumulation on the W chromosomes. AB - Approximately 90 species in the genus Leporinus (Characiformes, Anostomidae) are known, and most of them do not present differentiated sex chromosomes. However, there is a group of 7 species that share a heteromorphic ZW sex system. In all of these species, the W chromosome is the largest one in the karyotype and is mostly heterochromatic. We investigated the distribution of several microsatellites in the genome of 4 Leporinus species that possess ZW chromosomes. Our results showed a very large accumulation of mostly microsatellites on the W chromosomes. This finding supports the presence of an interconnection between heterochromatinization and the accumulation of repetitive sequences, which has been proposed for sex chromosome evolution, and suggests that heterochromatinization is the earlier of the 2 processes. In spite of the common origin that has been proposed for W chromosomes in all of the studied species, the microsatellites followed different evolutionary trajectories in each species, which indicates a high plasticity for sex chromosome differentiation. PMID- 24217022 TI - Stereotactic neurosurgical technique and electrophysiological study in ablating the ventromedial shell of the nucleus accumbens. AB - OBJECTIVE: To describe in as much detail as possible the method for ablating the ventromedial shell of the nucleus accumbens (NAc) and investigate the efficacy and safety of the ablation treatment. METHODS: Sixty-five patients with drug addictions received operations within the time frame from 2004 to 2009. The ablation targets were located in the bilateral medial posterior inferior shell of the NAc. Intraoperative electrophysiological monitoring was performed. RESULTS: Tissue impedance in the shell of the NAc varied from 185 to 355 Omega. When stimulated with a low frequency (2 Hz) and a voltage above 3 V, 57 out of 65 (87.7%) patients experienced slight throbbing sensations. During the lesion procedure, fever was detected on the head and face of 59 patients (90.8%), the heart rate decreased in 19 cases (29.2%), and restlessness, irritability and hyperalgia were noted for all patients. Among the 65 patients, 52 (80%) no longer experienced a psychological craving for the drug. CONCLUSIONS: The shell of the NAc may be a promising surgical target for psychosurgery. Electrophysiological recordings revealed that the shell is indeed an appropriate structure. PMID- 24217025 TI - The E280A presenilin mutation reduces voltage-gated sodium channel levels in neuronal cells. AB - BACKGROUND: Familial Alzheimer's disease (FAD) mutations in presenilin (PS) modulate PS/gamma-secretase activity and therefore contribute to AD pathogenesis. Previously, we found that PS/gamma-secretase cleaves voltage-gated sodium channel beta2-subunits (Navbeta2), releases the intracellular domain of Navbeta2 (beta2 ICD), and thereby, increases intracellular sodium channel alpha-subunit Nav1.1 levels. Here, we tested whether FAD-linked PS1 mutations modulate Navbeta2 cleavages and Nav1.1 levels. OBJECTIVE: It was the aim of this study to analyze the effects of PS1-linked FAD mutations on Navbeta2 processing and Nav1.1 levels in neuronal cells. METHODS: We first generated B104 rat neuroblastoma cells stably expressing Navbeta2 and wild-type PS1 (wtPS1), PS1 with one of three FAD mutations (E280A, M146L or DeltaE9), or PS1 with a non-FAD mutation (D333G). Navbeta2 processing and Nav1.1 protein and mRNA levels were then analyzed by Western blot and real-time RT-PCR, respectively. RESULTS: The FAD-linked E280A mutation significantly decreased PS/gamma-secretase-mediated processing of Navbeta2 as compared to wtPS1 controls, both in cells and in a cell-free system. Nav1.1 mRNA and protein levels, as well as the surface levels of Nav channel alpha-subunits, were also significantly reduced in PS1(E280A) cells. CONCLUSION: Our data indicate that the FAD-linked PS1(E280A) mutation decreases Nav channel levels by partially inhibiting the PS/gamma-secretase-mediated cleavage of Navbeta2 in neuronal cells. PMID- 24217026 TI - Food additives and behavior in 8- to 9-year-old children in Hong Kong: a randomized, double-blind, placebo-controlled trial. AB - OBJECTIVES: To test the individual effect of artificial food colorings (AFCs) and a preservative on the behavior of the general Chinese population. METHOD: One hundred thirty children (70 boys and 60 girls) in Hong Kong with a mean age of 8.64 years were enlisted to the study with a within-subject crossover between AFCs, a preservative (sodium benzoate), and a placebo capsule. Two behavior scores were used including the strengths and weaknesses of attention deficit hyperactivity disorder and normal behavior rating scale and the child behavior checklist-teacher report form. RESULTS: Capsule A containing AFCs and Capsule B containing sodium benzoate had no significant adverse effect compared with placebo in both behavior scores. This result persisted when analysis was restricted to children with 85% consumption of capsule (per protocol analysis). CONCLUSION: There seem to be no significant associations between AFCs and a preservative on Chinese children's behavior at the age of 8 to 9 years. Future directions and implications of this research are discussed. PMID- 24217027 TI - Continuing issues with the Bayley-III: where to go from here. PMID- 24217028 TI - Parental influence on a child's autistic traits. AB - CASE: Robbie is a 4-year-old boy whose parents are concerned about his speech, social skills, and repetitive behaviors. He has poor articulation; at time, he is difficult to understand. On the other hand, he has a fair vocabulary, and he has good intent to communicate. He is generally able to communicate his needs and wants. He likes to tell his parents about his day. When he begins the day at preschool, Robbie initially stands by himself and watches. He slowly warms up and eventually participates in activities. He engages in parallel play or follows other children. He knows names of children at preschool, and he is well liked. He is affectionate with his parents. When Robbie is excited, he wiggles his fingers, flaps his arms, and grimaces. He can be quite rigid; for example, he gets very distressed when his mother sets his cup down on his right side instead of his left. However, in general, Robbie has a sunny personality. He likes to watch children's television shows. He pretends plays with action figures. Robbie is an only child who lives with both parents. His mother works full-time, and his father is in home with Robbie during the day. When examined in the office, Robbie had a bright affect, good eye contact, and social referencing. He demonstrated good communicative intent, but poor articulation and some jargoning. He frequently wiggled his fingers and flapped his hands with excitement. Robbie had a borderline score on the Autism Diagnostic Observation Schedule. During the visit, the pediatrician noted that Robbie's father was rather quiet and rarely responded to questions. When he did respond, he had a monotone quality to his voice. He maintained either a flat or nervous affect throughout the visit. He made limited eye contact, and occasionally he stared excessively. PMID- 24217029 TI - Parental attributions for the behavior problems of children and adolescents with autism spectrum disorders. AB - OBJECTIVE: The authors examined parental attributions for child behavior problems in 63 married couples of children and adolescents (aged 3-20 years) with autism spectrum disorders (ASDs). Both child-referent attributions (i.e., beliefs about causes related to the child or adolescent) and parent-referent attributions (i.e., beliefs about causes related to the parent) were examined along the dimensions of locus, stability, and controllability. Parent and child/adolescent factors related to parental attributions were identified, and the associations between parental attributions and parenting burden were explored. METHOD: Mothers and fathers independently completed self-reported measures of parental attributions, parenting burden, and child behavior problems. Couples jointly reported on their son or daughter's severity of autism symptoms, intellectual disability status, age, and gender. RESULTS: Parents tended to attribute the behavior problems of their child/adolescent with an ASD to characteristics that were not only internal to and stable in the child/adolescent but also controllable by the child/adolescent. Mothers were more likely to attribute their son or daughter's behavior problems to characteristics that were less internal to and less stable in the child/adolescent with an ASD than were fathers. In addition, parents with a higher level of symptoms of the broader autism phenotype, parents of younger children, and parents of children/adolescents with intellectual disability, a higher severity of autism symptoms, and a higher severity of overall behavior problems were more likely to attribute their son or daughter's behavior problems to characteristics that were more internal to and stable in the child/adolescent and factors that were less controllable by the child/adolescent. Parental attributions were related to parents' level of parenting burden. IMPLICATIONS: Findings have implications for designing appropriate interventions and services for families of children and adolescents with ASDs. PMID- 24217030 TI - Sleep disorders in preschoolers: prevalence and comorbidity with psychiatric symptoms. AB - OBJECTIVES: This study provides data on the prevalence of diagnosable sleep disorders in preschoolers and examined the relationship between specific sleep disorders and a range of DSM-4-defined psychiatric symptoms. METHODS: All children born in 2003 or 2004 in Trondheim, Norway, who attended regular community health checkups for 4 year olds were asked to participate (97.2% attendance; 82.0% consent rate, N = 2475). A screen-stratified subsample of 1250 children was recruited to participate in an additional comprehensive study that included a structured diagnostic interview (the Preschool-Age Psychiatric Assessment). Nine hundred ninety-five parents (79.6%) completed the interview. RESULTS: The estimated sleep disorder rate was 19.2%. Rates of specific disorders were as follows: primary insomnia (16.6%), primary hypersomnia (0.8%), nightmare disorder (2.2%), and sleepwalking disorder (0.7%). When adjusted for a range of common psychiatric symptoms, primary insomnia was specifically related to symptoms of depression, generalized anxiety disorder, separation anxiety, and specific phobia. When sleep problems were excluded as a symptom of depression, the association between depression and primary insomnia was no longer significant. Nightmare disorder was significantly related to generalized anxiety disorder. CONCLUSIONS: This first study of the prevalence and comorbidity of diagnosable sleep disorders in preschoolers indicates that primary insomnia is common in young children, whereas other sleep disorders are rare. Sleep disorders are related to psychiatric symptoms, particularly symptoms of anxiety disorders. PMID- 24217031 TI - The average human being harbors 10 times more bacterial cells than their own cell numbers. PMID- 24217032 TI - Initial intestinal colonization in the human infant and immune homeostasis. AB - The paradigm of disease burden in the developed world has changed drastically in the last few decades from predominately infections to immune-mediated diseases (autoimmunity and allergy) because of alterations in the Western lifestyle (improved sanitation, immunizations, antibiotic usage and altered dietary intake). A diverse balanced microbiota is necessary for the development of an appropriate innate and adaptive immune response. There is strong evidence that disruption of the normal colonization process can lead to alterations in the important symbiotic relationship that is necessary for immune homeostasis. For example, infants born by cesarean section or receiving excessive perinatal antibiotics have inadequate initial colonization and aberrant mucosal immune function. As a result, later in childhood, they express an increased incidence in asthma and autoimmune diseases (e.g. celiac disease). An important component of initial colonization is the infant's diet. Breast milk contains a variety of nondigestible oligosaccharides which function as prebiotics preferentially stimulating proliferation of Bifidobacteria and Lactobacilli, important health promoting bacteria, and cause fermentation of the oligosaccharides into short chain fatty acids. In the absence of breastfeeding for the first 6 months of life, formula containing pre- and probiotics may overcome an initial inadequate colonization process and help establish a normal mucosal immune system. PMID- 24217033 TI - Reshaping the gut microbiota at an early age: functional impact on obesity risk? AB - Overweight and obesity can currently be considered a major threat to human health and well-being. Recent scientific advances point to an aberrant compositional development of the gut microbiota and low-grade inflammation as contributing factors, in conjunction with excessive energy intake. A high-fat/energy diet alters the gut microbiota composition, which reciprocally engenders excessive energy harvesting and storage. Further, microbial imbalance increases gut permeability, leading to metabolic endotoxemia, inflammation and insulin resistance. Local intestinal immunologic homeostasis is achieved by tolerogenic immune responses to microbial antigens. In the context of amelioration of insulin sensitivity and decreased adiposity, the potential of gut microbiota modulation with specific probiotics and prebiotics lies in the normalization of aberrant microbiota, improved gut barrier function and creation of an anti-inflammatory milieu. This would suggest a role for probiotic/prebiotic interventions in the search for preventive and therapeutic applications in weight management. PMID- 24217034 TI - Clinical consequences of diet-induced dysbiosis. AB - Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium. This is followed by a summary of clinical evidence of diet-induced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial profile will be reviewed. PMID- 24217035 TI - The human microbiome and probiotics: implications for pediatrics. AB - Steady advances in our knowledge of the composition and function of the human microbiome at multiple body sites including the gut, skin and airways will likely contribute to our understanding of mechanisms of probiotic action by beneficial microbes. Microbe:microbe and microbe:human interactions are important considerations as we select probiotics for pediatric patients in the future. Although our knowledge about the composition of the microbiome is progressing rapidly, many gaps exist about the functional capacity and metabolic machinery of the human microbiome. Based on a limited amount of data, probiotics appear capable of altering the composition and function of the microbiome. Probiotics may be part of dietary strategies that combine ways to enhance microbiome function with nutrients that may be converted to active compounds promoting human health. Probiotics have yielded beneficial effects in numerous studies in the context of different diseases in pediatric gastroenterology. These disease states include necrotizing enterocolitis, antibiotic-associated diarrhea and colitis, acute gastroenteritis and irritable bowel syndrome. In the skin and airways, it is unclear if probiotics can affect the function of the microbiome to reduce the impact of diseases such as asthma and atopic dermatitis. An enhanced understanding of the effects of probiotics on the microbiome should facilitate selection of optimal probiotic strains for specific diseases in the future. PMID- 24217036 TI - Host-guest self-assembly in block copolymer blends. AB - Ultrafine, uniform nanostructures with excellent functionalities can be formed by self-assembly of block copolymer (BCP) thin films. However, extension of their geometric variability is not straightforward due to their limited thin film morphologies. Here, we report that unusual and spontaneous positioning between host and guest BCP microdomains, even in the absence of H-bond linkages, can create hybridized morphologies that cannot be formed from a neat BCP. Our self consistent field theory (SCFT) simulation results theoretically support that the precise registration of a spherical BCP microdomain (guest, B-b-C) at the center of a perforated lamellar BCP nanostructure (host, A-b-B) can energetically stabilize the blended morphology. As an exemplary application of the hybrid nanotemplate, a nanoring-type Ge2Sb2Te5 (GST) phase-change memory device with an extremely low switching current is demonstrated. These results suggest the possibility of a new pathway to construct more diverse and complex nanostructures using controlled blending of various BCPs. PMID- 24217037 TI - Subacromial impingement syndrome--effectiveness of physiotherapy and manual therapy. AB - BACKGROUND: The subacromial impingement syndrome (SIS) includes the rotator cuff syndrome, tendonitis and bursitis of the shoulder. Treatment includes surgical and non-surgical modalities. Non-surgical treatment is used to reduce pain, to decrease the subacromial inflammation, to heal the compromised rotator cuff and to restore satisfactory function of the shoulder. To select the most appropriate non-surgical intervention and to identify gaps in scientific knowledge, we explored the effectiveness of the interventions used, concentrating on the effectiveness of physiotherapy and manual therapy. METHODS: The Cochrane Library, PubMed, EMBASE, PEDro and CINAHL were searched for relevant systematic reviews and randomised clinical trials (RCTs). Two reviewers independently extracted data and assessed the methodological quality. A best-evidence synthesis was used to summarise the results. RESULTS: Two reviews and 10 RCTs were included. One RCT studied manual therapy as an add-on therapy to self-training. All other studies studied the effect of physiotherapy: effectiveness of exercise therapy, mobilisation as an add-on therapy to exercises, ultrasound, laser and pulsed electromagnetic field. Moderate evidence was found for the effectiveness of hyperthermia compared to exercise therapy or ultrasound in the short term. Hyperthermia and exercise therapy were more effective in comparison to controls or placebo in the short term (moderate evidence). For the effectiveness of hyperthermia, no midterm or long-term results were studied. In the midterm, exercise therapy gave the best results (moderate evidence) compared to placebo or controls. For other interventions, conflicting, limited or no evidence was found. CONCLUSIONS: Some physiotherapeutic treatments seem to be promising (moderate evidence) to treat SIS, but more research is needed before firm conclusions can be drawn. PMID- 24217038 TI - A snapshot of cardiovascular diseases in Africa in the new millennium. PMID- 24217039 TI - Left atrial appendage closure in patients with atrial fibrillation in whom warfarin is contra-indicated: initial South African experience. AB - Atrial fibrillation is a common cause of cardiac embolic events, especially stroke. Oral anticoagulation therapy is used to reduce these events. Many patients however are unable to take such therapy. Percutaneous occlusion of the left atrial appendage (the source of 90% of these emboli) is an option in these patients. Presented here are the first 12 patients to have this procedure done in South Africa. PMID- 24217041 TI - Pattern of congestive heart failure in a Kenyan paediatric population. AB - BACKGROUND: Heart failure in children is a common cause of morbidity and mortality, with high socio-economic burden. Its pattern varies between countries but reports from Africa are few. The data are important to inform management and prevention strategies. OBJECTIVE: To describe the pattern of congestive heart failure in a Kenyan paediatric population. METHODS: This was a retrospective study done at Kenyatta National Hospital, Nairobi Kenya. Records of patients aged 12 years and younger admitted with a diagnosis of heart failure between January 2006 and December 2010 were examined for mode of diagnosis, age, gender, cause, treatment and outcome. Data were analysed using the Statistical Programme for Social Scientists version 16.0 for windows, and presented in tables, bar and pie charts. RESULTS: One hundred and fifty-eight cases (91 male, 67 female) patients' records were analysed. The mean age was 4.7 years, with a peak at 1-3 years. The male: female ratio was 1.4:1. All the cases were in New York Heart Association (NYHA) class II-IV. Evaluation of infants was based on the classification proposed by Ross et al. (1992). Diagnosis was made based on symptoms and signs combined with echocardiography (echo) and electrocardiography (ECG) (38%); echo alone (12.7%); ECG, echo and chest X-ray (CXR) (11.4%); and ECG alone (10.8%). The underlying cause was established on the basis of symptoms, signs, blood tests, CXR, echo and ECG results. Common causes were infection (22.8%), anaemia (17.1%), rheumatic heart disease (14.6%), congenital heart disease (13.3%), cardiomyopathy (7.6%), tuberculosis and human immunodeficiency virus (6.9% each); 77.9% of patients recovered, 13.9% after successful surgery, and 7.6% died. CONCLUSION: Congestive heart failure is not uncommon in the Kenyan paediatric population. It occurs mainly before five years of age, and affects boys more than girls. The majority are due to infection, anaemia, and rheumatic and congenital heart diseases. This differs from those in developed countries, where congenital heart disease and cardiomyopathy predominate. The majority of children usually recover. Prudent control of infection and correction of anaemia are recommended. PMID- 24217040 TI - Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study. AB - BACKGROUND: Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur. METHODS: A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH. RESULTS: TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis. CONCLUSION: This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation. PMID- 24217042 TI - Comparison of results of autologous versus homologous blood transfusion in open heart surgery. AB - BACKGROUND: The aim of this study was to determine a method to decrease the use of homologous blood during openheart surgery using a simple blood-conservation protocol. We removed autologous blood from the patient before bypass and used isovolumetric substitution. We present the results of this protocol on morbidity and mortality of surgery patients from two distinct time periods. METHODS: Patients from the two surgical phases were enrolled in this retrospective study in order to compare the outcomes using autologous or homologous blood in open heart surgery. A total of 323 patients were included in the study. The autologous transfusion group (group 1) comprised 163 patients and the homologous transfusion group (group 2) 160 patients. In group 1, autologous bloods were prepared via a central venous catheter that was inserted into the right internal jugular vein in all patients, using the isovolumetric replacement technique. The primary outcome was postoperative In-hospital mortality and mortality at 30 days. Secondary outcomes included the length of stay in hospital and in intensive care unit (ICU), time for extubation, re-intubations, pulmonary infections, pneumothorax, pleural effusions, atrial fibrillation, other arrhythmias, renal disease, allergic reactions, mediastinitis and sternal dehiscence, need for inotropic support, and low cardiac-output syndrome (LCOS). RESULTS: The mean ages of patients in groups 1 and 2 were 64.2 +/- 10.3 and 61.5 +/- 11.6 years, respectively. Thirty-eight of the patients in group 1 and 30 in group 2 were female. There was no in-hospital or 30-day mortality in either group. The mean extubation time, and ICU and hospital stays were significantly shorter in group 1. Furthermore, postoperative drainage amounts were less in group 1. There were significantly fewer patients with postoperative pulmonary complications, pneumonia, atrial fibrillation and renal disease. The number of patients who needed postoperative inotropic support and those with low cardiac output was also significantly less in group 1. CONCLUSION: Autologous blood transfusion is a safe and effective method in carefully selected patients undergoing cardiac surgery. It not only prevents transfusion-related co-morbidities and complications but also enables early extubation time and shorter ICU and hospital stay. Furthermore, it reduces the cost of surgery. PMID- 24217043 TI - Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital. AB - INTRODUCTION: Rheumatic heart disease (RHD) frequently occurs following recurrent episodes of acute rheumatic fever (ARF). Benzathine penicillin (benzapen) is the most effective method for secondary prophylaxis against ARF whose efficacy largely depends on adherence to treatment. Various factors determine adherence to therapy but there are no data regarding current use of benzapen in patients with RHD attending Mulago Hospital. The study aims were (1) to determine the levels of adherence with benzapen prophylaxis among rheumatic heart disease patients in Mulago Hospital, and (2) establish the patient factors associated with adherence and, (3) establish the reasons for missing monthly benzathine penicillin injections. METHODS: This was a longitudinal observational study carried out in Mulago Hospital cardiac clinics over a period of 10 months; 95 consecutive patients who satisfied the inclusion criteria were recruited over a period of four months and followed up for six months. Data on demographic characteristics and disease status were collected by means of a standardised questionnaire and a card to document the injections of benzapen received. RESULTS: Most participants were female 75 (78.9%). The age range was five to 55 years, with a mean of 28.1 years (SD 12.2) and median of 28 years. The highest education level was primary school for most patients (44, 46.3%) with eight (8.4%) of the patients being illiterate. Most were either NYHA stage II (39, 41.1%) or III (32, 33.7%). Benzathine penicillin adherence: 44 (54%) adhered to the monthly benzapen prophylaxis, with adherence rates >= 80%; 38 (46%) patients were classified as non-adherent to the monthly benzapen, with rates less than 80%. The mean adherence level was 70.12% (SD 29.25) and the median level was 83.30%, with a range of 0-100%; 27 (33%) patients had extremely poor adherence levels of <= 60%. Factors associated with adherence: higher education status, residing near health facility favoured high adherence, while painful injection was a major reason among poor performers. CONCLUSION: The level of non-adherence was significantly high (46%). Residence in a town/city and having at least a secondary level of education was associated with better adherence, while the painful nature of the benzapen injections and lack of transport money to travel to the health centre were the main reasons for non-adherence among RHD patients in Mulago. PMID- 24217045 TI - Is double-blinding possible while administering fluids in the intensive care unit? PMID- 24217044 TI - Cardiovascular haemodynamics in pre-eclampsia using brain naturetic peptide and tissue Doppler studies. AB - AIM: To determine early haemodynamic changes in preeclampsia (PE) using tissue Doppler echocardiography and brain natriuretic peptide (BNP), and to relate these changes to obstetric outcomes. METHODS: Consenting primigravidae patients in the third trimester of pregnancy were included in the study, which was carried out in a large regional hospital in Durban, South Africa; 115 primigravidae (52 pre eclamptics and 63 normotensive pregnant patients) attending the maternity unit including the antenatal clinics at the study site were studied. The patients, matched for maternal and gestational age, were examined during pregnancy and within the puerperium. Transthoracic echocardiography (TTE), tissue Doppler imaging (TDI), umbilical artery Doppler and laboratory investigations were performed. RESULTS: BNP levels were significantly increased in the antepartum period [23.8 (2-184.1) vs 6.0 (0.5-45.2) pmol/l; p < 0.0001] and during labour [15.0 (1.8-206.4) vs 8.7 (1.9-24.8) pmol/l; p < 0.01] in the pre-eclamptic group compared to the normotensive controls. In the postpartum period, mean BNP levels were 4.2 (1.7-51.4) and 5.95 (2.2-38.7) pmol/l in the preeclamptic and normotensive groups, respectively (p > 0.05). Tissue Doppler Em/Ea ratios were elevated in the pre-eclamptic compared to the normotensive group (11.02 +/- 5.6 vs 9.16 +/- 2.6; p < 0.05). Mean left atrial size was larger (38 mm) in the pre eclamptic group than in the normotensive group (35 mm) but this difference was not significant (p > 0.05). The umbilical artery resistance index was significantly higher in the pre-eclamptic group compared to the normotensive group (0.68 +/- 0.06 vs 0.63 +/- 0.05; p < 0.001). There was an increased rate of Caesarean sections performed in the pre-eclamptic group (n = 24) compared to the normotensive group (n = 18; p < 0.001). There were two stillbirths in the pre eclamptic group and none in the normotensive group. As expected, birth weight (2.6 +/- 0.8 kg vs 3.14 +/- 0.42 kg; p < 0.0001) was lower in the pre-eclamptic group compared to the normotensive group. CONCLUSION: In pregnancies complicated by pre-eclampsia, BNP levels were increased in comparison to normotensive pregnancies and this was accompanied by early changes in left ventricular diastolic function as determined by the tissue Doppler Em/Ea ratios. These changes reverted to baseline values, as indicated by return of BNP levels in the pre-eclamptic group to levels seen in the normotensive group. These changes were associated with an increased Caesarean section rate and lower birth weights in pre-eclamptic mothers. PMID- 24217046 TI - Bilateral thoracoscopic sympathectomy for primary hyperhydrosis: a review of 335 cases. AB - OBJECTIVE: The goal of this retrospective study was to evaluate the outcomes of bilateral video-assisted thoracoscopic sympathectomy for primary hyperhydrosis. METHODS: Between January 2007 and December 2011, a total of 335 patients (192 male, 143 female, mean age 28.3 years) who underwent bilateral thoracoscopic sympathectomy for primary hyperhydrosis were reviewed retrospectively. RESULTS: Hyperhydrosis occurred in the palmar and axillary region in 175 (52.23%) patients, in only the palmar region in 52 (15.52%), in the craniofacial region in 44 (13.13%), in only the axillary region in 42 (12.53%), and in the palmar and pedal regions in 22 (6.56%) patients. Bilateral thoracoscopic sympathectomy was performed in all patients. The mean follow-up period was 24 (6-48) months. The initial cure rate was 95% and the initial satisfaction rate was 93%. There was no mortality in this study. The complication rate was 15.82% in 53 patients. CONCLUSION: Video-assisted thoracoscopic sympathectomy for the treatment of primary hyperhydrosis was effective, with low rates of morbidity and mortality. Despite the appearance of postoperative complications, such as compensatory sweating, patient satisfaction with the procedure was high and their quality of life improved. PMID- 24217047 TI - The global burden of congenital heart disease. AB - Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. In a country with a fertility rate of about eight per woman, the population has to support four times as many children with CHD as in a country with a fertility rate of two. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity. Countries with high fertility rates have more children with congenital heart disease per wage earner. Improving local health services and controlling infectious diseases (diarrhoeal illness, rheumatic fever, measles, rotoviral infection) are important but are mere 'band-aids' compared to improving education, empowering women and reducing birth rates. PMID- 24217048 TI - Congress report: Cardiology and Diabetes at the Limits, 22-25 March 2013. PMID- 24217049 TI - A novel intermediate in the LiAlH4-LiNH2 hydrogen storage system. AB - The decomposition pathways for the composite LiAlH4-LiNH2 in different ratios of (1 : 1), (1 : 1.5), (1 : 2) and (1 : 2.5) have been systematically studied using in situ synchrotron radiation powder X-ray diffraction (SR-PXD) as well as simultaneous thermogravimetric analysis and differential scanning calorimetry coupled with mass spectroscopy. The study reveals that LiAlH4 decomposes in two steps to LiH, Al and H2 and, subsequently, the produced LiH reacts with LiNH2 forming Li2NH and H2. A new intermediate, Li(4-x)Al(x)(NH)(2-2x)N(2x), is observed during the decomposition of LiAlH4-LiNH2 (1 : 1.5), (1 : 2) and (1 : 2.5), formed from Li2NH and Al prior to the formation of Li3AlN2. Li(4 x)Al(x)(NH)(2-2x)N(2x) is characterized by Rietveld refinement of SR-PXD data and solid-state (27)Al MAS NMR spectroscopy (chemical shift, delta(Al) = 125 ppm) and both techniques reveal a maximum value for x of ~0.10, i.e., Li(3.90)Al(0.10)(NH)(1.80)N(0.20). The solid solution Li(4-x)Al(x)(NH)(2-2x)N(2x) crystallizes in a cubic unit cell, a = 4.9854(7) A with space group Fm3m, similar to the crystal structure for Li2NH and is a rare type with both cation and anion disorder. For LiAlH4-LiNH2 (1 : 1) 8.7 wt% of H2 is released during heating from RT to 500 degrees C, while for LiAlH4-LiNH2 composites with molar ratios of LiNH2 higher than 0.5 the release of both H2 and NH3 is observed. PMID- 24217059 TI - Validation of the Basic Erosive Wear Examination. AB - The Basic Erosive Wear Examination (BEWE) is a practical index for screening tooth wear, using a 4-point ordinal scale (0-3). The highest score is recorded in each sextant and a total score (or BEWE sextant cumulative) is calculated per subject. This study aims to investigate if the BEWE sextant cumulative score compares to one comprising a percentage score from all tooth surfaces and as a highest BEWE per subject. The aim is to assess the validity of this score. A total of 350 subjects were recruited from hospital and general practice in south east England. Buccal, occlusal and lingual/palatal BEWE scores were collected and percentages calculated based on scores 1, 1 and above, 2 and above and 3. BEWE sextant cumulative scores and highest BEWE scores were also recorded per subject. Spearman's correlation coefficients (p values) assessed the relationship between BEWE sextant cumulative scores, BEWE percentages and BEWE highest score per subject. The BEWE sextant cumulative score correlates significantly to a BEWE score taken as a percentage score from all tooth surfaces (Spearman's r > 0.5, p < 0.001) and especially to BEWE surface scores of 1 and above and 2 and above (r > 0.8, p < 0.001) and as a highest surface score per subject (r > 0.8, p < 0.001). BEWE sextant score provides a representation of tooth wear on all tooth surfaces. This study validates a tooth wear index, which provides clinicians with risk indicators of a patient's level of tooth wear and may help to guide clinical management. PMID- 24217060 TI - A self-switchable Ag nanoreactor exhibiting outstanding catalytic properties. AB - A highly efficient nanoreactor that contains silver nanoparticles in hollow silica spheres and an interpolymer network as a gate-keeper has been developed following a facile procedure. The fast "signal-triggered" switch of the smart network results in a high reactivity and a high response rate, yielding improved potential for many practical applications. PMID- 24217062 TI - Clustering of excess health concerns for electromagnetic fields among health personnel: A quantitative and qualitative approach. AB - Clustering patterns, among health-care personnel, of excessive concerns pertaining to perceived electromagnetic field-related health impacts, as contrasted to those from other environmental factors, were explored. Knowledge/excessive concerns of 722 health-care personnel were assessed using a 22-item structured questionnaire along with a double-phase qualitative study comprising semistructured interviews and focus groups. Over 75 percent of the participants had high perceived knowledge, whereas accuracy was limited to <20 percent and correctness to 8 percent. An "excessive concern" group was clearly distinguished from a "relaxed attitude" one. Clustering of excessive concerns may derive from personal beliefs, suggesting a risk governance issue for health education policies. PMID- 24217063 TI - Visualising future behaviour: Effects for snacking on biscuit bars, but no effects for snacking on fruit. AB - In this study, participants (N = 223) were randomised to visualise snacking on fruit, visualise snacking on biscuit bars or no visualisation, and intentions and attitudes towards fruit and biscuit bars, immediate selection of fruit or biscuit bars and subsequent consumption were measured. No effects of visualising snacking on fruit were found once background variables were taken into account. Visualising snacking on biscuit bars, however, resulted in greater intentions to consume biscuit bars (smallest beta = 0.19, p < 0.01). These findings suggest that specifics of the visualised target behaviour may be important in visualisation. Further investigation is needed before recommending visualisation for increasing fruit consumption. PMID- 24217064 TI - Negative emotions and stigma associated with a human papillomavirus test result: A comparison between human papillomavirus-positive men and women. AB - Human papillomavirus has largely been framed as a women's health issue, and the psychosocial impact of human papillomavirus among men remains unclear. In this study, we found that women infected with human papillomavirus (n = 154) experienced a greater degree of negative emotions and stigma than human papillomavirus-infected men (n = 190). Among women, younger age and less education were associated with greater expression of negative emotions and stigma. Conversely, being single was significantly associated with a greater degree of negative emotions and stigma beliefs among men. These findings suggest the need to re-frame messages that both men and women receive regarding human papillomavirus. PMID- 24217065 TI - Brief report: Maternal posttraumatic stress symptoms are related to adherence to their child's diabetes treatment regimen. AB - Although research suggests that posttraumatic stress disorder symptoms in relation to physical health diagnoses may be related to poor adherence to treatment regimens, so far, whether parental posttraumatic stress disorder symptoms have an impact on their child's adherence to insulin-dependent diabetes mellitus treatment has not been investigated. Using self-report questionnaires, the present study found that children of mothers who have posttraumatic stress disorder symptoms in relation to their child's diagnosis of type I diabetes showed poorer adherence to treatment than the children of mothers without posttraumatic stress disorder. However, this was only the case for younger children (aged 0-8 years) where mothers played a more active role in their child's treatment. PMID- 24217066 TI - The effect of slow coronary flow on right and left ventricular performance. AB - OBJECTIVE: To evaluate left and right ventricular functions using tissue Doppler echocardiography (TDE) and myocardial performance index (MPI) methods in patients with slow coronary flow (SCF) and to determine the relationship between these parameters and thrombolysis in myocardial infarction frame count in SCF patients. SUBJECTS AND METHODS: Thirty-five patients (20 males and 15 females) with SCF who underwent coronary angiography and 35 age- and sex-matched controls (14 males and 21 females) without SCF who underwent elective coronary angiography were enrolled in the study. Left ventricular (LV) and right ventricular (RV) functions were examined using conventional echocardiography and TDE. RESULTS: LV systolic myocardial velocity (Sm), early myocardial velocity (Em), late myocardial velocity (Am), and Em/Am ratio were similar in both the SCF and control groups; however, isovolumetric relaxation time (IRT) was higher in the SCF group compared to the control group (IRT: 99 +/- 17 vs. 88 +/- 20; p = 0.01). In patients with SCF, LV MPI was higher than in the control group, but this was not statistically significant (0.61 +/- 0.11 vs. 0.56 +/- 0.12; p = 0.07). The RV tricuspid annular velocities and MPI were similar in the SCF and control groups. CONCLUSION: This study showed that SCF affected LV functions echocardiographically and could cause partially reduced LV performance. In addition, SCF did not affect RV functions echocardiographically. PMID- 24217067 TI - Development and evaluation of a LOR-based image reconstruction with 3D system response modeling for a PET insert with dual-layer offset crystal design. AB - In this study we present a method of 3D system response calculation for analytical computer simulation and statistical image reconstruction for a magnetic resonance imaging (MRI) compatible positron emission tomography (PET) insert system that uses a dual-layer offset (DLO) crystal design. The general analytical system response functions (SRFs) for detector geometric and inter crystal penetration of coincident crystal pairs are derived first. We implemented a 3D ray-tracing algorithm with 4pi sampling for calculating the SRFs of coincident pairs of individual DLO crystals. The determination of which detector blocks are intersected by a gamma ray is made by calculating the intersection of the ray with virtual cylinders with radii just inside the inner surface and just outside the outer-edge of each crystal layer of the detector ring. For efficient ray-tracing computation, the detector block and ray to be traced are then rotated so that the crystals are aligned along the X-axis, facilitating calculation of ray/crystal boundary intersection points. This algorithm can be applied to any system geometry using either single-layer (SL) or multi-layer array design with or without offset crystals. For effective data organization, a direct lines of response (LOR)-based indexed histogram-mode method is also presented in this work. SRF calculation is performed on-the-fly in both forward and back projection procedures during each iteration of image reconstruction, with acceleration through use of eight-fold geometric symmetry and multi-threaded parallel computation. To validate the proposed methods, we performed a series of analytical and Monte Carlo computer simulations for different system geometry and detector designs. The full-width-at-half-maximum of the numerical SRFs in both radial and tangential directions are calculated and compared for various system designs. By inspecting the sinograms obtained for different detector geometries, it can be seen that the DLO crystal design can provide better sampling density than SL or dual-layer no-offset system designs with the same total crystal length. The results of the image reconstruction with SRFs modeling for phantom studies exhibit promising image recovery capability for crystal widths of 1.27 1.43 mm and top/bottom layer lengths of 4/6 mm. In conclusion, we have developed efficient algorithms for system response modeling of our proposed PET insert with DLO crystal arrays. This provides an effective method for both 3D computer simulation and quantitative image reconstruction, and will aid in the optimization of our PET insert system with various crystal designs. PMID- 24217068 TI - Oral findings and clinical implications of patients with congenital neutropenia: a literature review. AB - Neutropenia is a granulocyte disorder characterized by a dramatically low number of neutrophils, the most important type of white blood cell. The condition results in susceptibility to severe pyogenic infections. Some people are born with it (congenital neutropenia), and others develop it as young children. The disease is so-called chronic neutropenia when lasting more than two months. This article reviews the definition, clinical properties and common oral manifestations of congenital neutropenia in order to highlight the importance of diagnosis, oral hygiene maintenance and dental treatments. PMID- 24217069 TI - Hemolytic uremic syndrome outbreak in Turkey in 2011. AB - The aim of this retrospective multicenter study was to define the epidemiological and clinical features and prognostic factors of the first diarrhea-related hemolytic uremic syndrome (D+HUS) outbreak in Turkey in 2011. All pediatric nephrology centers in Turkey were asked about D+HUS patients via e-mail. Seventy D+HUS patients (median age: 5.7 years) participated. The seasonal peak was around the 7th, 8th and 9th months with 44 cases, centered in the east Marmara region. No causative agent could be identified. The rate of neurological complications and mortality was 21.4% and 4.2%, respectively. Eculizumab was used in four cases. Two of them had severe neurological complications despite plasma exchange. Elevated polymorphonuclear leukocyte count during hospital admission was the predictor of both severe disease and poor outcome. Duration of prodrome was the predictor of poor outcome (p<0.05). In conclusion, the median age of the affected children was greater than in the previous reports, while clinical features and outcome were similar. PMID- 24217070 TI - Acute disseminated encephalomyelitis: an evaluation of 15 cases in childhood. AB - To describe our experience with acute disseminated encephalomyelitis (ADEM) and the relationships between the clinical course, magnetic resonance imaging (MRI) findings and treatment, a retrospective record review was conducted of 15 children who were admitted with the diagnosis of ADEM during the period 2004 2010. Their ages ranged between 2 and 13 years. Patients presented most often with ataxia (53.3%) and secondly with weakness and headache (46.6%). Myelitis was determined in two patients. Five patients were treated with high-dose intravenous (IV) methylprednisolone followed by oral prednisolone, seven patients were treated with oral prednisolone, one patient was treated with plasmapheresis with IV immunoglobulin (Ig), and one patient was treated with IVIg. We observed recurrence in one patient. ADEM is a demyelinating disorder that is being diagnosed increasingly more as MRI studies are performed more frequently in patients with acute encephalopathy. Early diagnosis and therapy might improve the outcome. PMID- 24217071 TI - The relationship between renal P-glycoprotein expression and response to steroid therapy in childhood nephrotic syndrome. AB - In this study, we aimed to investigate the relationship between renal P glycoprotein (rP-gp) expression and response to corticosteroid therapy in childhood nephrotic syndrome (NS). Expression of rP-gp was evaluated prior to non steroid immunosuppressive therapy in children with NS (Group 1), prior to any treatment in children with immunoglobulin (Ig)A nephropathy (Group 2), and during renal donation in healthy adults (Group 3); mesangial proliferation was evaluated in Groups 1 and 2. Total dosage of steroid was calculated in Group 1. The ratio of rP-gp (+) glomeruli was higher in Group 1 than Group 3 (33.8 +/- 27.1% vs 4.7 +/- 4.6%, p=0.000). There were no rP-gp (+) glomeruli in Group 2. The rate of mesangial proliferation was similar in Groups 1 and 2. There was no statistically significant correlation between rP-gp expression and total steroid dosage (r=0.455, p=0.160). Our findings showed that rP-gp expression is increased in patients receiving steroid therapy for NS regardless of the cumulative steroid dosage and mesangial cell proliferation. PMID- 24217072 TI - Oncologic manifestations in children with neurofibromatosis type 1 in Turkey. AB - Children with neurofibromatosis type 1 (NF1) are predisposed to malignancies such as brain tumors, leukemia, and pheochromocytomas. The aim of this study was to evaluate malignancy in patients with NF1. We studied 120 patients with NF1 in this study. Demographic data from these patients were retrospectively reviewed. We found 20 malignancies in 19 patients in our study. Ten children with NF1 had optic glioma. Four children had solid central nervous system tumors (3 pilocytic astrocytomas, 1 glioblastoma multiforme). Three patients had myeloid malignancies (1 juvenile myelomonocytic leukemia, 1 acute myeloid leukemia, 1 acute lymphocytic leukemia). Hodgkin lymphoma, T-cell lymphoblastic lymphoma, and malignant triton tumor were found in one patient each. Patients with NF1 are predisposed to both benign and malignant tumors of neurogenic and non-neurogenic origin. Therefore, systematic medical follow-up in patients with NF1 is important. PMID- 24217074 TI - Acute flaccid paralysis surveillance in southeastern Turkey, 1999-2010. AB - The aim of the study was to report the results of acute flaccid paralysis (AFP) surveillance and to evaluate the performance of surveillance in the southeastern region of Turkey in the 12 years from 1999 to 2010. We investigated cases in seven provinces of the southeastern region of Turkey. In the evaluation, AFP Case Report Form, Laboratory Investigation Form and 60-Day Case Investigation Form were used; individuals' demographic characteristics, clinical findings, status of vaccination, sample results, and 60-day follow-up were evaluated. Incidence ranged from 0.60/100,000 in 2008 to 1.60/100,000 in 1999. Dysstasia and loss of strength were the most frequently reported prodromal symptoms. Coxsackievirus and echoviruses were the most frequent viruses detected. One-quarter of the AFP cases could not be followed up in the present surveillance system. PMID- 24217073 TI - Selenium levels, selenoenzyme activities and oxidant/antioxidant parameters in H1N1-infected children. AB - Selenium (Se) is an essential trace element, and it shows its biological functions within low molecular Se compounds and Se-containing proteins, known as "selenoproteins". Glutathione peroxidases (GPxs) and thioredoxin reductases (TrxRs) are the most important selenoproteins functioning as antioxidant enzymes. These enzymes protect the body from the endogenous products of cellular metabolism that have been implicated in DNA damage, mutagenesis, and carcinogenesis. H1N1 virus is a subtype of the influenza A virus and was an endemic in humans in 2009 and 2010. Taking into account the high incidence of Se deficiency and the high mortality and morbidity rates in H1N1 infection, this study was designed to investigate the plasma and erythrocyte Se levels, selenoenzyme activities and other oxidant/antioxidant parameters in H1N1-infected children during the 2009-2010 pandemic. We observed a significant increase in C reactive protein levels (245%) and marked decreases in both plasma and erythrocyte Se levels (11%, both) and in GPx1 (45%), GPx3 (16%) and TrxR (30%) activities in H1N1-infected children compared to the control group. In addition, significant decreases were observed in erythrocyte catalase (CAT) (38%), total superoxide dismutase (SOD) (42%) and glutathione S-transferase (GST) (19%) activities and in erythrocyte total glutathione (GSH) (18%) and plasma GSH (10%) concentrations, while marked increases were observed in plasma lipid peroxidation levels (27%). However, we did not find a significant difference in selenoprotein P (SePP) levels between the groups. Our findings show that Se-dependent and independent blood redox systems are down-regulated in H1N1 influenza. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in infections, particularly in H1N1 influenza. PMID- 24217075 TI - Diet and physical activity interventions do have effects on body composition and metabolic syndrome parameters in overweight and obese adolescents and their mothers. AB - To determine the effects of lifestyle intervention and diet on body composition, anthropometric measurements, and metabolic syndrome (MS) in obese and overweight adolescents and their mothers, a diet and lifestyle intervention program was administered for 16 weeks to 19 9-17-year-old (12.52 +/- 2.85 years) adolescents (female/male, 8/11) with a body mass index (BMI) value over the 90th percentile; hemoglobin (Hb)A1C, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fibrinogen, and C-reactive protein levels of the adolescents and anthropometric measurements of the mothers were compared. In some of the anthropometric values (body weight (BW), BMI, waist circumference (WC), skinfold thicknesses, body fat tissue, and lean tissue mass), a statistically significant difference was observed in pre- and post-application measurements (p<0.05). There was a significant difference in pre- and post-application values of systolic and diastolic blood pressure and some biochemical parameters (uric acid, total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, and HOMA-IR) (p<0.05); however, there was no significant difference in pre- and post-application values of fasting blood glucose, aspartate transaminase, alanine transaminase, albumin, HbA1C, fasting insulin, and fibrinogen (p>0.05). MS was observed in 52.6% of the participants at baseline, and this rate was found as 15.8% based on the measurements carried out at week 16, which is a statistically significant decrease (p<0.05). There was a statistically significant difference in pre- and post-study values of BW, BMI, body fat mass, basal metabolic rate, WC, hip circumference, hip/waist, and skinfold thickness in mothers. A 16-week diet and lifestyle intervention program for overweight and obese adolescents involving their mothers resulted in significant improvement in obesity and MS treatment. PMID- 24217076 TI - Declining male births in Germany before and after reunification. AB - Male births occur 3% in excess of female births in mammals in a ratio (M/F) of 0.515. Many factors have been shown to influence this, including socioeconomic deprivation. This paper reviews live birth data for Germany over the period 1946 2009, and identifies secular trends in M/F pre- and post-reunification. The null hypothesis is that there were no differences between East and West Germany, geographically or temporally, before and after reunification. Annual data on male and female live births were obtained from the Human Mortality Database and analyzed with contingency tables. These data were available separately for East and West Germany (1950-1989). There was a significant decline in M/F in both German Republics overall and before reunification (p<0.0001). No decline was present after. Pre-reunification, West Germany had a lower overall M/F than East Germany (p=0.001). In conclusion, a declining M/F has been shown in many countries over the past decades. The two German Republics' M/F fell prior to reunification and the economic collapse of East Germany. Contracting societies that offer poor socioeconomic conditions (such as the communist former East Germany) may result in a decrease in M/F, but this is not reflected in the data, which show that M/F in West Germany prior to reunification was lower than in East Germany. This is not explicable with the contracting economies hypothesis; other and as yet unknown influences may have modified M/F trends anticipated by known variables. PMID- 24217077 TI - Poor postnatal weight gain predicts stage 3+ retinopathy of prematurity in very low birth weight infants. AB - Multiple systemic risk factors are associated with retinopathy of prematurity (ROP). We analyzed the role of low weight gain (WG) to predict the development of stage 3+ ROP among preterm infants. This study included 126 newborns with birth weight <=1500 g and gestational age <32 weeks. Preterm newborn infants were divided into two groups according to severity of ROP as: preterm infants without ROP or mild ROP (Group 1) and preterm infants with stage 3+ ROP (Group 2). WG and WG proportion were measured at completed 4 and 6 weeks of life. The patients under the cut-off point according to receiver operating characteristic curve were classified as low WG patients. WG and WG proportion were significantly lower in Group 2 than in Group 1 at the 4th and 6th weeks of life. We concluded that low WG and WG proportion at the 4th and 6th weeks of life were predictive for the development of stage 3+ ROP. Preterm babies with low birth weight and low WG should be followed closely for severe ROP. PMID- 24217078 TI - The mechanical properties and stiffness of aorta in obese children. AB - Obesity in children has also been associated with the development of early cardiovascular abnormalities. The aim of this study was to investigate the relationship between aortic stiffness and some risk factors in obese children. Sixty obese children and 60 age- and sex-matched healthy controls were assessed. The mechanical property parameters were measured or computed: lumen diastolic and systolic diameters, aortic strain and elastic modules. Compared to controls, obese children had altered stiffness values of the aorta, whereas strain was not different. Compared to controls, obese children had higher systolic and diastolic blood pressure values. Insulin level, homeostasis model assessment (HOMA) score, and total cholesterol, triglycerides, lowdensity lipoprotein (LDL), and leptin levels were significantly higher, while adiponectin, high-density lipoprotein (HDL) levels and quantitative insulin sensitivity check index (QUICKI) scores were significantly lower in obese children than in controls. Obesity in children increases aortic stiffness, which suggests that the joint effect of insulin resistance, serum leptin and adipokine levels and obesity can have a considerable impact on preclinical arterial changes and could play an important role in the early pathophysiology of macrovascular disease. PMID- 24217079 TI - Diagnostic dilemma in autoinflammatory disease in two patients: does the name matter? AB - The systemic autoinflammatory diseases are inflammatory disorders characterized by uncontrolled inflammation of the innate immune system. A common monogenic autoinflammatory disease is familial Mediterranean fever (FMF), associated with mutations in the MEFV gene. Another autoinflammatory disease group is cryopyrin associated periodic syndromes (CAPS), which are characterized by urticarial rash and mutations of the gene NLRP. Systemiconset juvenile idiopathic arthritis (soJIA) is classified as a multifactorial autoinflammatory disease. We report two cases of systemic autoinflammatory disease with homozygous E148Q mutation in the FMF gene. They had unusual features, such as urticarial rash, non-erysipeloid erythema, lymphadenopathy, and hepatosplenomegaly, and neurological findings in one. These patients met the "definition" criteria for FMF with two mutations in the MEFV gene. They fit the "description" criteria for CAPS with their fever, urticaria, and other clinical features. They also met the "classification" criteria for soJIA, with the fever, rash, arthritis, and accompanying systemic features. PMID- 24217080 TI - Kawasaki disease shock syndrome: a severe form of Kawasaki disease. AB - Kawasaki disease is a systemic vasculitis, primarily encountered in children. Its clinical presentation is well known, and coronary artery abnormalities are classical complications. Shock is not a common form of presentation of the disease. We report a case who presented with shock due to Kawasaki disease in accordance with the recently defined 'Kawasaki disease shock syndrome'. In pediatric intensive care units, Kawasaki disease shock syndrome may be misdiagnosed as toxic shock syndrome. Intensivists and emergency room physicians should be aware of this uncommon presentation and perform an echocardiography to search for coronary involvement in case of clinical doubt. PMID- 24217082 TI - Rhabdomyolysis due to isoniazid poisoning resulting from the use of intramuscular pyridoxine. AB - Isoniazid is an effective antituberculosis drug. Isoniazid poisoning produces a characteristic clinical syndrome that occurs 30 to 120 minutes after ingestion and includes seizures, metabolic acidosis, and in severe cases, coma. Rhabdomyolysis is one of the reported complications of isoniazid poisoning, but relevant data are limited. Parenteral pyridoxine is the antidote of isoniazid. In this case, a 16-year-old male patient admitted to the Pediatric Emergency Department two hours after isoniazid poisoning. For treatment, intramuscular pyridoxine was used, but he developed serious rhabdomyolysis. PMID- 24217081 TI - Thyroid hormone resistance: a novel mutation in thyroid hormone receptor beta (THRB) gene - case report. AB - Thyroid hormone resistance (THR) is a dominantly inherited syndrome characterized by reduced sensitivity to thyroid hormones. It is usually caused by mutations in the thyroid hormone receptor beta (THRB) gene. In the present report, we describe the clinical and laboratory characteristics and genetic analysis of patients with a novel THRB gene mutation. The index patient had been misdiagnosed as hyperthyroidism and treated with antithyroid drugs since eight days of age. Thyroid hormone results showed that thyrotropin (thyroid-stimulating hormone, TSH) was never suppressed despite elevated thyroid hormone levels, and there was no symptom suggesting hyperthyroidism. A heterozygous mutation at codon 350 located in exon 9 of the THRB gene was detected in all the affected members of the family. It is important to consider thyroid hormone levels in association with TSH levels to prevent inappropriate treatment and the potential complications, such as clinical hypothyroidism or an increase in goiter size. PMID- 24217083 TI - Selective proximal renal tubular involvement and dyslipidemia in two cousins with oculocerebrorenal syndrome of Lowe. AB - Oculocerebrorenal syndrome of Lowe (OCRL) is a rare, X-linked disorder characterized by congenital cataracts, neonatal or infantile hypotonia, seizures, cognitive impairment, and renal tubular dysfunction. In this article, we report two maternal cousins with OCRL with a hemizygous p.Ala788Asp mutation in exon 22 of the OCRL gene. They presented with diverse features of selective proximal renal tubular defect and high serum levels of total cholesterol, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). PMID- 24217084 TI - Pseudoarthrosis of the hand in neurofibromatosis type 1: a case report. AB - Neurofibromatosis (NF) is a disorder with a wide spectrum of clinical manifestations. Here, we describe a 16-year-old boy with NF1 who had pseudoarthrosis of the 4th and 5th fingers of the left hand. He had specific cutaneous lesions and Lisch nodules in the iris. Because NF1 affects multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy. PMID- 24217085 TI - Munchausen syndrome by proxy presented as recurrent respiratory arrest and thigh abscess: a case study and overview. AB - While many physicians are familiar with the sexual or physical abuse of children, there is little awareness about Munchausen syndrome by proxy (MSBP). As case reports of MSBP increase, awareness among physicians is thought to increase as well. We thus present herein a 16-month-old girl who admitted to Hacettepe University Ihsan Dogramaci Children's Hospital with the complaint of seizure, recurrent apnea and thigh abscess, who was later diagnosed as MSBP. The case was being followed by the Child Protection Team of the hospital (Haceteppe University Child Protection Unit [HU-CPU]). HU-CPU contributed to the early detection of this case and protected the child from a possible fatal outcome. The mother was confronted for MSBP and refused to take responsibility for her child's symptoms. As seen in this case, when MSBP is suspected, psychiatric evaluation of the mother, evaluation of the mother-child interaction and collection of a detailed family and social history can have a positive impact on the prognosis in these cases. This case report underlines the importance of multidisciplinary team work to share the responsibility and reduce the burden during the treatment process of these difficult and complicated cases. PMID- 24217086 TI - Hemophagocytosis in a case with Crimean-Congo hemorrhagic fever and an overview of possible pathogenesis with current evidence. AB - Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic condition characterized by high fever, hepatosplenomegaly, cytopenia, hyperferritinemia, and increased hemophagocytic macrophage proliferation and activation in the reticuloendothelial system. Primary HLH is familial and is a fatal disease that begins during early childhood. Secondary HLH may be acquired after intense activation of the immune system due to infection. Clinical and biologic symptoms result from cytokines secreted by T-lymphocytes and macrophages. Subtypes of primary HLH are caused by genetic defects in several cell types, including perforin-dependent cytotoxic T-lymphocytes and natural killer (NK) cells. Secondary HLH is often associated with intracellular pathogen infections. Crimean Congo hemorrhagic fever (CCHF) is caused by a tick-borne virus, Nairovirus, from the Bunyaviridae family. It is characterized by a poor prognosis and has a high mortality. We report the case of a 14-year-old boy living in a CCHF-endemic area with no history of tick exposure. He presented with fever, and laboratory tests showed bicytopenia and hemophagocytosis in the bone marrow aspiration. Blood samples were polymerase chain reaction (PCR)-negative for CCFH but immunoglobulin (Ig)M-positive. In conclusion, patients with hemophagocytosis should be assessed for CCHF during the evaluation of cytopenia. PMID- 24217088 TI - Early-onset basal cell carcinoma. AB - Basal cell carcinoma (BCC) is a common skin cancer that is responsible for approximately 75% of non-melanoma skin cancers. BCC occurs on sunexposed areas in fair-skinned individuals; frequency increases with age and peaks in the seventh decade of life. Although it usually occurs in the elderly population, it has been reported in children as well. Here, we present a case of BCC in an eight-year-old child without any predisposing characteristics. PMID- 24217087 TI - Neurophysiological follow-up of two siblings with Crigler-Najjar syndrome type I and review of literature. AB - Crigler-Najjar syndrome type I is an autosomal recessive inherited disease and rarely seen in childhood. Bilirubin neurotoxicity is the morbidity of the disease due to the elevated unconjugated bilirubin levels. Mental retardation, seizures, cognitive dysfunction, oculomotor nerve palsy, ataxia, choreoathetosis, and spasticity may be seen. Due to the high bilirubin levels, alterations in the neurophysiological studies may be detected. In this study, we describe two siblings who were diagnosed with Crigler-Najjar syndrome type I who underwent a successful liver transplantation using a single cadaveric organ, together with their neurophysiological follow-up and review of the literature. PMID- 24217089 TI - Blue rubber bleb nevus disease. PMID- 24217092 TI - Multi-perpetrator domestic violence. AB - A significant proportion of reports of domestic violence against women involve multiple perpetrators. Although the number of perpetrators has been consistently identified as a measure of abuse severity, only a minority of studies of domestic violence examine the role of multiple offenders. Data on multi-perpetrator domestic violence (MDV) is frequently removed from analysis in domestic violence studies, or multi-perpetrator incidents are treated as single-perpetrator incidents. However, the available research links MDV to negative mental and physical health outcomes, intimate partner homicide, homelessness among women, and severe mental illness and suicidality. This article reviews the available prevalence data on MDV and draws together research on the contexts in which MDV takes place. It highlights two groups that are particularly vulnerable to MDV: (1) girls and women partnered to members of gangs and organized crime groups and (2) girls and women in some ethnic minority communities. While discussions of honor in relation to domestic violence are often racialized in Western media, this article highlights the cross-cultural role of masculine honor in collective violence against women in the working class and impoverished communities of majority cultures as well as in migrant and ethnic minority communities. It is clear that such complex forms of violence present a range of challenges for intervention and treatment and the article emphasizes the need for specialized and coordinated modes of investigation, support, and care. PMID- 24217090 TI - PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist. AB - There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic beta cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP 1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas. PMID- 24217091 TI - Programmed death ligand-1 expression in non-small cell lung cancer. AB - Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway. PMID- 24217093 TI - Rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. RA is considered an autoimmune disease. A study in the UK found the population minimum prevalence of RA is 1.16% in women and 0.44% in men. In Australia, the estimated prevalence is 0.6%. Using BEACH data from April 2011 to March 2013, we examined the rate of RA and its management in Australian general practice. PMID- 24217094 TI - Osteoarthritis: Where are we for pain and therapy in 2013? AB - BACKGROUND: Osteoarthritis is the leading musculoskeletal cause of disability in western society. General practitioners are central in the management of patients with osteoarthritis. OBJECTIVE: To review the literature on factors associated with pain in osteoarthritis and discuss the implications of these findings for management. DISCUSSION: It is well known that there is a modest correlation between X-ray changes and pain, mainly because an X-ray is a poor measure of what is happening in the joint. For example, in the knee, there is consistent evidence that bone marrow lesions, synovitis/effusions and cartilage defects are associated with knee pain and cartilage loss. In addition, muscle strength and obesity are predictors of pain, even in structurally normal knees. Lastly, central factors and genetic factors have been implicated in the pain experience. Thus, osteoarthritis is an umbrella term for a number of pathways that lead to very similar pain and structural outcomes, which is leading to lesion-specific therapies, indicating the importance of trying to pinpoint causes of pain in the individual. PMID- 24217095 TI - Viral arthritis. AB - BACKGROUND: Arthralgia is a common presentation to general practice, and many cases will not require any specific treatment. It is important to differentiate viral arthritis from other causes as early intervention in inflammatory arthritis has been shown to improve long-term outcome. OBJECTIVE: This article provides a review of the different causes of viral arthritis, with an emphasis on recognising the clues to a viral cause, and summarises appropriate investigations and management. DISCUSSION: Viral arthritis is typically self-limiting and requires no specific intervention, although in rare cases symptoms can be prolonged. Some viruses have a predilection for the joints, and arthritis is one of the common presenting signs of infection. It may also be a manifestation of important treatable viral infections such as hepatitis and human immunodeficiency virus (HIV). Early systemic inflammatory arthritis can be difficult to differentiate from viral arthritis and should be actively considered in all patients. Comprehensive testing for viral aetiologies is of limited utility. PMID- 24217096 TI - An approach to neck pain for the family physician. AB - BACKGROUND: Neck pain is a common presentation in general practice. Nevertheless, recommendations for the investigation and management of neck pain lack a strong evidence base and are predominantly extrapolated from low back pain studies. OBJECTIVE: This review provides an investigation and treatment paradigm to help primary care physicians assess and manage cervical spine pain. DISCUSSION: Although sinister causes of neck pain are rare, clinicians must be mindful of red flags that may indicate serious pathology. The medical interview, rather than the physical examination, remains the most critical step in determining the likely cause of cervical spine pain, whereas biochemical tests and imaging are not part of routine assessment. The classification of neck pain into acute or chronic patterns, extrapolated from the low back pain literature, may help stratify the need for intervention and the likely prognosis of neck pain. A more concerted research effort is needed to help better understand and develop evidence-based guidelines for the management of neck pain. PMID- 24217097 TI - Ankylosing spondylitis: an update. AB - BACKGROUND: Ankylosing spondylitis (AS) affects one in 200 individuals and is usually diagnosed many years after onset of symptoms. Chronic back pain is common and recognition of early disease requires clinical experience and a high index of suspicion. Further, inflammatory markers are not invariably elevated and radiographic changes are often late findings. OBJECTIVE: The objective of this review is to address AS and the recently defined disorder of non-radiographic axial spondyloarthritis. The latter is a common early presentation of AS, before the development of radiographic sacroiliitis, and will evolve into typical AS in 50% of patients. DISCUSSION: MRI may be particularly useful in evaluating early disease, although chronic changes of sacroiliitis are better seen on plain X rays. Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy and recent studies suggest that regular use among patients with AS slows radiographic progression. Tumour necrosis inhibitor therapy has strikingly improved quality of life for the more than two-thirds of AS patients with an inadequate response to NSAIDs. PMID- 24217098 TI - REM sleep behaviour disorder - More than just a parasomnia. AB - BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by loss of the usual muscle atonia that occurs during REM sleep, allowing patients to act out their dreams. OBJECTIVE: This article aims to draw attention to RBD, allowing early recognition and treatment. SUMMARY: As RBD patients are at high risk of hurting themselves and their bed partners while acting out their dreams, improving safety within the bedroom environment and treatment with exogenous melatonin or clonazepam are recommended. Longitudinal studies have shown that the onset of idiopathic RBD may be an early warning sign of specific neurodegenerative diseases. PMID- 24217099 TI - Acute scrotal pain. AB - BACKGROUND: Acute scrotal pain, once diagnosed, can be treated appropriately with either conservative or surgical measures. The complexity lies in the use of history, clinical examination and investigations in a restricted time frame, to identify the appropriate management path. OBJECTIVE: To evaluate the literature regarding important and common differentials of acute scrotal pain with the intent to enable primary care doctors to appropriately assess and manage the acutely painful scrotum. DISCUSSION: Since there is no single feature in the history, examination or investigation that is pathognomonic in diagnosing acute scrotal pain, the triad together is pivotal in its clinical evaluation. If there is any suspicion of testicular torsion, a prompt referral to a surgeon with relevant experience or to the emergency department may salvage the testis. Epididymitis and torsion of the appendix testis may be managed conservatively once testicular torsion has been ruled out. PMID- 24217100 TI - MRI brain imaging. AB - General practitioners (GPs) are expected to be allowed to request MRI scans for adults for selected clinically appropriate indications from November 2013 as part of the expansion of Medicare-funded MRI services announced by the Federal Government in 2011. This article aims to give a brief overview of MRI brain imaging relevant to GPs, which will facilitate explanation of scan findings and management planning with their patients. Basic imaging techniques, common findings and terminology are presented using some illustrative case examples. PMID- 24217101 TI - Recurrent renal colic - A case study. AB - A previously well woman, 44 years of age, presented with 3 years of recurrent bilateral renal colic. Despite an increase in fluid intake and a low calcium diet, the intermittent episodes of renal colic continued and had become more frequent in the last year. An abdominal X-ray was performed, which showed some radio-opaque areas on both renal silhouettes (see Figure 1). Two stones in the right pelvic ureter were also seen following administration of contrast. No obstruction of the urinary tract was evident. Urinalysis revealed leukocyturia, a pH of 6.5 and specific gravity of 1.015. Blood testing showed hypercalcaemia of 2.96 mmol/L and hypophosphataemia of 0.71 mmol/L. PMID- 24217102 TI - Hairy elbows - A case study. AB - A boy aged 6 years was referred to our clinic for evaluation of the presence of fair, thin hair on both of his elbows. This condition had first been observed when he was 2 years of age and the hair had subsequently increased in length and thickness (Figure 1). He had a history of asthma and was being treated by a paediatrician. His family medical record was otherwise unremarkable. This unusual hairiness was symmetrically distributed on the extensor surfaces of both proximal forearms and distal arms. The underlying skin showed no abnormalities. No hypertrichosis was found elsewhere and examination of teeth, skeleton and fingernails was also normal. No other morphological changes were noted. In addition, his height was appropriate for his age. No developmental, mental or physical impairment was observed. The blood cell count and general biochemistry, as well as thyroid and sexual hormonal profiles were all normal. Radiological examination, which was performed on the parents' request, was normal. The boy was diagnosed with hypertrichosis cubiti (HC), and shaving of the areas was recommended. PMID- 24217103 TI - Internet-based cognitive behaviour therapy for depression and anxiety. AB - Internet-based, or computerised, cognitive behaviour therapy (CBT) can be used to treat patients with depression or anxiety. Patients are engaged in structured programs of care, with several programs available either at no cost or moderate cost. Internet CBT (iCBT) may be particularly suited to patients with mobility issues or living in rural or remote areas. Although there are no adverse effects, clinicians should assess patients for risk issues and the need for more immediate assistance before recommending iCBT. Monitoring effectiveness of any intervention for the patient is important. iCBT has National Health and Medical Research Council (NHMRC) Level I evidence of efficacy. PMID- 24217104 TI - Interpersonal relationships for patients with irritable bowel syndrome: a qualitative study of GPs' perceptions. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder and general practitioners (GPs) are in the front line of care. Supportive interpersonal relationships are integral to successful management and prognosis of IBS. Yet GPs' perceptions of helping patients manage interpersonal problems are unknown. METHODS: Thirteen GPs (3 women, 10 men) participated in semi-structured interviews. The data were analysed thematically. RESULTS: Three main themes were identified. Most GPs had not actively considered that living with IBS could contribute to patients' inter-personal problems. GPs viewed interpersonal relationships as potentially triggering or exacerbating IBS symptoms. Their approach was to proactively identify interpersonal problems in order to manage the related symptoms. DISCUSSION: IBS is a chronic illness that is difficult to manage for patients and doctors alike. Recognising the potential interpersonal impact of IBS and referring patients to appropriate services where necessary could improve patient health outcomes as well as the doc-tor-patient relationship. PMID- 24217105 TI - General practitioners' challenges during the 2009/A/H1N1 vaccination campaigns in Australia, Israel and England: a qualitative study. AB - BACKGROUND: The 2009/A/H1N1 influenza vaccination campaign was managed mainly by general practitioners (GPs); however, little is known about the challenges GPs encountered during the vaccination campaign. AIM: To analyse the challenges GPs encountered during the 2009/A/H1N1 vaccination campaign. METHODS: In-depth, semi structured qualitative interviews were conducted with GPs in Australia, Israel and England, and subjected to thematic analysis. RESULTS: GPs experienced different levels of autonomy when organising vaccinations in clinics. Their significant role was the provision of advice about the vaccine to the patients. This role was challenged by the necessity to provide the advice as a response to the anti-vaccination messages in the media and because GPs harboured doubts about mass vaccination policies. DISCUSSION: It is important that GPs accept the rationale behind vaccination campaigns and should be given accurate information about the vaccine before the campaign commences. Trustful, two-way channels for communication between GPs and public health authorities should also be established. PMID- 24217106 TI - Validation of a general practice audit and data extraction tool. AB - BACKGROUND: We assessed how accurately a common general practitioner (GP) audit tool extracts data from two software systems. METHODS: First, pathology test codes were audited at 33 practices covering nine companies. Second, a manual audit of chronic disease data from 200 random patient records at two practices was compared with audit tool data. RESULTS: Pathology review: all companies assigned correct codes for cholesterol, creatinine and glycated haemoglobin; four companies assigned incorrect codes for albuminuria tests, precluding accurate detection with the audit tool. Case record review: there was strong agreement between the manual audit and the tool for all variables except chronic kidney disease diagnoses, which was due to a tool-related programming error. DISCUSSION: The audit tool accurately detected most chronic disease data in two GP record systems. The one exception, however, highlights the importance of surveillance systems to promptly identify errors. This will maximise potential for audit tools to improve healthcare quality. PMID- 24217107 TI - Data extraction from electronic health records - existing tools may be unreliable and potentially unsafe. AB - BACKGROUND: The increasing use of routinely collected data in electronic health record (EHR) systems for business analytics, quality improvement and research requires an extraction process fit for purpose. Little is known about the quality of EHR data extracts. We examined the accuracy of three data extraction tools (DETs) with two EHR systems in Australia. METHODS: The hardware, software environment and extraction instructions were kept the same for the extraction of relevant demographic and clinical data for all active patients with diabetes. The counts of identified patients and their demographic and clinical information were compared by EHR and DET. RESULTS: The DETs identified different numbers of diabetics and measures of quality of care under the same conditions. DISCUSSION: Current DETs are not reliable and potentially unsafe. Proprietary EHRs and DETs must support transparency and independent testing with standardised queries. Quality control within an appropriate policy and legislative environment is essential. PMID- 24217108 TI - A is for aphorism - 'Wherever the art of medicine is loved there is also a love of humanity'. AB - He was an amazing diagnostician. He could listen to the history and then with this long, pointy, bony finger he'd say, "So, what do you think was significant in that bit of the history? What did you feel there as you examined the abdomen? Did you look at this here? Have you seen these?" But he was a very warm person too - just so caring. PMID- 24217109 TI - Revalidation - a personal reflection. AB - BACKGROUND: The review of a doctor's fitness to practice is being increasingly discussed internationally. The Medical Board of Australia has recently announced a desire to explore this issue. The United Kingdom (UK) introduced revalidation for doctors last year. The UK revalidation system is an enhancement of the National Health Service appraisal system that requires doctors to participate in annual appraisals conducted by trained peers. The appraisal process involves four stages: submission of a range of information; a confidential appraisal discussion; a personal development plan; and a post-appraisal sign-off. The criteria that doctors are assessed against are detailed in the General Medical Council's guidelines of Good Medical Practice. Satisfactory participation in the appraisal process over a 5-year cycle is likely to result in a recommendation for successful revalidation. OBJECTIVE: To describe the UK revalidation system and to share my personal reflection about the revalidation process. DISCUSSION: The revalidation process has been beneficial from a personal perspective, but the range of consequences and subsequent support mechanisms need to be considered and addressed. PMID- 24217110 TI - Diffusely infiltrating central nervous system lymphoma involving the brainstem in an immune-competent patient. PMID- 24217111 TI - Over 35% liquid-state 13C polarization obtained via dissolution dynamic nuclear polarization at 7 T and 1 K using ubiquitous nitroxyl radicals. AB - The most versatile method to increase liquid-state (13)C NMR sensitivity is dissolution dynamic nuclear polarization. The use of trityl radicals is usually required to obtain very large (13)C polarization via this technique. We herein demonstrate that up to 35% liquid-state (13)C polarization can be obtained in about 1.5 h using ubiquitous nitroxyl radicals in (13)C-labeled sodium salts by partially deuterating the solvents and using a polarizer operating at 1 K and 7 T. PMID- 24217112 TI - Moderate physical exercise results in increased cell activity in articular cartilage of the knee joint in rats. AB - BACKGROUND: Moderate exercise regimens have shown minor positive effects on matrix turnover in articular cartilage (AC), while effects at cellular level, e.g. proliferation, are scarcely described. AIM: The aim of this study was to investigate the effects of moderate exercise on cell proliferation and recruitment of cells possibly active in regeneration in different regions of cartilage in the rat knee joint. METHODS: Eighteen rats were orally given 5-bromo 2-deoxyuridine (BrdU) for 14 days for in vivo DNA labeling. Nine rats underwent treadmill training for 50 min/day, 5 days/week (exercise group), and 9 rats served as controls (no exercise). Animals were sacrificed after 14, 56 and 105 days, and knee joints were harvested. BrdU+ cells were visualized immunohistochemically (IHC) and counted in AC, posterior stem cell niche (PN), potential migration route (PMR; area between PN and the AC border), potential migration area (PMA; region between PN and AC including PN) and epiphyseal cartilage plate (EP) of the tibia and femur. RESULTS: Compared to controls, in the exercise group BrdU+ cells/mm(2) were increased on days 14 (p = 0.022) and 105 (p = 0.045) in AC of the tibia and on day 105 (p = 0.014) in AC of the femur. BrdU+ cell numbers were increased in the PMR region of the tibia on days 14 (p = 0.023) and 105 (p = 0.0018) and in the PMR region of the femur on day 105 (p = 0.0099) as well as in the PMA region of the tibia (p = 0.0008) and femur (p = 0.0080) on day 105. No significant differences in BrdU+ cells/mm(2) were seen in PN or EP between the groups at any time point. Regarding collagen 2A1 expression and proteoglycan accumulation, no significant differences between groups were detected. CONCLUSIONS: The results indicate increased cell activity in AC in response to physical exercise and may help to understand the complexity of AC regeneration in the normal mammal knee joint. PMID- 24217113 TI - Use of an artificial neural network for diagnosis of facial pain syndromes: an update. AB - BACKGROUND: Based on a classification scheme for facial pain syndromes and a binomial (yes/no) facial pain questionnaire, we previously reported on the ability of an artificial neural network (ANN) to recognize and correctly diagnose patients with different facial pain syndromes. OBJECTIVES: We now report on an updated questionnaire, the development of a secure web-based neural network application and details of ANNs trained to diagnose patients with different facial pain syndromes. METHODS: Online facial pain questionnaire responses collected from 607 facial pain patients (395 female, 65%, ratio F/M 1.86/1) over 5 years and 7 months were used for ANN training. RESULTS: Sensitivity and specificity of the currently running ANN for trigeminal neuralgia type 1 and trigeminal neuralgia type 2 are 92.4 and 62.5% and 87.8 and 96.4%, respectively. Sensitivity and specificity are 86.7 and 95.2% for trigeminal neuropathic pain, 0 and 100% for trigeminal deafferentation pain and 100% for symptomatic trigeminal neuralgia and postherpetic neuralgia. Sensitivity is 50% for nervus intermedius neuralgia (NIN) and 0% for atypical facial pain (AFP), glossopharyngeal neuralgia (GPN) and temporomandibular joint disorder (TMJ). Specificity for AFP, NIN and TMJ is 99% and for GPN, 100%. CONCLUSIONS: We demonstrate the utilization of question-based historical self-assessment responses used as inputs to design an ANN for the purpose of diagnosing facial pain syndromes (outputs) with high accuracy. PMID- 24217115 TI - Heterogeneity of mesenchymal markers expression-molecular profiles of cancer cells disseminated by lymphatic and hematogenous routes in breast cancer. AB - Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination. PMID- 24217116 TI - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) Signaling Capacity and the Epithelial Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH)2D3 in NSCLC Treatment. AB - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDRhigh) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDRlow and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH)2D3 sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH)2D3 induces E cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH)2D3-mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH)2D3 opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH)2D3 may prevent lung cancer progression in a molecularly defined subset of NSCLC patients. PMID- 24217117 TI - Critical illness-related corticosteroid insufficiency in children. AB - Adequate adrenocortical function is essential for survival in critical illness. Most critically ill patients display elevated plasma cortisol concentrations, which reflects activation of the hypothalamic-pituitary-adrenal axis and is considered to be a homeostatic adaptation. However, many critically ill patients have 'relative' or 'functional' adrenal insufficiency, which is characterized by an inadequate production of cortisol in relation to an increased demand during periods of severe stress. Recently, the term 'critical illness-related corticosteroid insufficiency' (CIRCI) was coined. CIRCI occurs as a result of a decrease in adrenal steroid production or tissue resistance to glucocorticoids. An international task force of the American College of Critical Care Medicine issued recommendations for the diagnosis and management of this condition in adult patients. We review the prevalence, diagnosis, and therapeutic approach to adrenal insufficiency in critically ill children. We found a lack of consensus within the pediatric field as to the optimal approach to CIRCI, and call for an international task force to establish unified guidelines. PMID- 24217114 TI - Tumor metabolism of malignant gliomas. AB - Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation. PMID- 24217118 TI - The positive effect of moderate walking exercise on chemerin levels in Portuguese patients with type 2 diabetes mellitus. AB - BACKGROUND: Physical exercise intervention is known to be crucial in the management of type 2 diabetes mellitus (T2DM). We aimed to evaluate, in patients with T2DM, the effect of regular moderate walking exercise on markers of oxidative stress, lipid metabolism, and inflammation. METHODS: We studied 30 patients with T2DM who walked regularly during the last year and 53 patients with T2DM who did not perform any type of exercise. The patients were evaluated for chemerin, adiponectin, leptin, oxidized low-density lipoprotein, and C-reactive protein (CRP) levels. RESULTS: The active T2DM patients showed significantly lower body mass index, as compared with the inactive patients. The active T2DM patients showed significantly lower levels of chemerin and CRP than those of the inactive T2DM patients (CRP lost significance after adjustment for body mass index). The active patients, compared with the inactive, presented a trend toward higher levels of adiponectin and lower values of oxidized low-density lipoprotein. Leptin differed significantly between sexes, and the active women presented a trend toward lower levels as compared with the inactive women. CONCLUSIONS: In the patients with T2DM, the practice of moderate walking in a regular basis was sufficient to reduce chemerin levels, which suggests that practice of regular physical exercise should be encouraged. PMID- 24217119 TI - Elevated plasma fibrinogen levels are associated with a poor prognosis in patients with hepatocellular carcinoma. AB - OBJECTIVES: Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in cancer patients. We investigated the prognostic value of pretreatment plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and thirteen patients with newly diagnosed HCC were retrospectively evaluated. We investigated the correlation between pretreatment plasma fibrinogen levels, clinicopathological parameters and overall survival. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with overall survival. RESULTS: The median value of the pretreatment plasma fibrinogen level was 279 mg/dl. Elevated plasma fibrinogen levels were associated with larger tumor size, the presence of vascular invasion and higher Cancer Liver Italian Program scores. Lower plasma fibrinogen levels were associated with higher Child-Pugh grades. The overall survival rates in patients with pretreatment plasma fibrinogen levels >= 315 mg/dl were significantly lower than those with a pretreatment plasma fibrinogen level <315 mg/dl (p = 0.016). On multivariate analysis, the plasma fibrinogen levels (per 100 mg/dl) were found to be independently associated with overall survival (hazard ratio 1.236; p = 0.046). CONCLUSIONS: This study demonstrates that elevated pretreatment plasma fibrinogen levels are associated with tumor progression and are independently associated with a poor prognosis in patients with HCC. PMID- 24217120 TI - VX and VG chemical warfare agents bidentate complexation with lanthanide ions. AB - Investigations into V-agent interaction with 1,10-phenanthroline nitrate Ln(III) complexes (Eu and Tb) were carried out using luminescence and UV-Vis spectroscopy. Addition of several equivalents of agent resulted in the loss of luminescence intensity and the observation of free 1,10-phenanthroline by UV-Vis. We propose a displacement mechanism in which the V-agent acts as a bidentate ligand to the lanthanide ion. Association constants were determined by luminescence titrations and found to be 10(5) mol(-1) dm(3). PMID- 24217121 TI - NO2 bond cleavage by MoL3 complexes. AB - The cleavage of one N-O bond in NO2 by two equivalents of Mo(NRAr)3 has been shown to occur to form molybdenum oxide and nitrosyl complexes. The mechanism and electronic rearrangement of this reaction was investigated using density functional theory, using both a model Mo(NH2)3 system and the full [N((t)Bu)(3,5 dimethylphenyl)] experimental ligand. For the model ligand, several possible modes of coordination for the resulting complex were observed, along with isomerisation and bond breaking pathways. The lowest barrier for direct bond cleavage was found to be via the singlet eta(2)-N,O complex (7 kJ mol(-1)). Formation of a bimetallic species was also possible, giving an overall decrease in energy and a lower barrier for reaction (3 kJ mol(-1)). Results for the full ligand showed similar trends in energies for both isomerisation between the different isomers, and for the mononuclear bond cleavage. The lowest calculated barrier for cleavage was only 21 kJ mol(-1)via the triplet eta(1)-O isomer, with a strong thermodynamic driving force to the final products of the doublet metal oxide and a molecule of NO. Formation of the full ligand dinuclear complex was not accompanied by an equivalent decrease in energy seen with the model ligand. Direct bond cleavage via an eta(1)-O complex is thus the likely mechanism for the experimental reaction that occurs at ambient temperature and pressure. Unlike the other known reactions between MoL3 complexes and small molecules, the second equivalent of the metal does not appear to be necessary, but instead irreversibly binds to the released nitric oxide. PMID- 24217122 TI - Short- and long-term impact of subtotal parathyroidectomy on the achievement of bone and mineral parameters recommended by clinical practice guidelines in dialysis patients: a 12-year single-center experience. AB - BACKGROUND/AIMS: The short- and long-term impact of parathyroidectomy (PTX) on the parameters of mineral bone disease in dialysis patients with severe secondary hyperparathyroidism (HPT) remains unclear. METHODS: A retrospective chart review of 401 consecutive dialysis patients who underwent subtotal PTX by one surgeon was performed. We checked serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) for 3 consecutive days, and then monthly for Ca, P, and tri-monthly for iPTH postoperatively. Patients with available laboratory data within the 1st to 6th postoperative months were included in the short-term follow-up group and those with at least 6 months available data were in the long-term follow-up one. RESULTS: Patients (short-term group, n = 401, and long-term group, n = 94) had severely uncontrolled serum iPTH levels, Ca, P and Ca * P before PTX. In the short-term group, percentages of cases achieving K/DOQI targets for serum Ca, Ca * P, and iPTH and KDIGO ones for serum Ca, P, and iPTH after PTX, significantly improved compared with those before operation (all p < 0.05). In the long-term group (mean follow-up of 43 +/- 29 months), the percentage of achieved targets for serum iPTH in both guidelines and for serum Ca and Ca * P in the K/DOQI recommendation also improved postoperatively (all p < 0.05). CONCLUSIONS: Achievements of K/DOQI recommended values for serum Ca, Ca * P, iPTH and KDIGO recommendations for iPTH can be successfully reached by subtotal PTX in medically refractory, secondary HPT in dialysis patients both during short- and long-term follow-ups. PMID- 24217123 TI - Multi-slice computed tomography assessment of stent position in a patient with acute coronary syndrome and anomalous origin of the coronary arteries. AB - We describe the case of a woman with acute coronary syndrome who was treated by percutaneous coronary intervention (PCI) and stenting of the proximal right coronary artery, which shared its short origin with the left anterior descending artery. A multi-slice computed tomography study of the patient's coronary tree, performed after percutaneous treatment, played a fundamental role in obtaining a clearer view of the coronary anatomy, as well as of stent positioning in this particular anatomy, eliminating any doubt about the PCI result. PMID- 24217124 TI - Percutaneous balloon pericardiotomy using the Inoue balloon for patients with recurrent pericardial tamponade. AB - BACKGROUND: Recurrent pericardial effusion is often caused by pericardial metastases of extra-cardiac tumours. These effusions may be moderate to severe, leading to cardiac tamponade. The treatment is emergency pericardiocentesis but in spite of the initial success of that treatment, the effusions have high recurrence rates. Here we describe our experience of percutaneous balloon pericardiotomy (PBP) using the Inoue balloon for the management of three patients with malignant pericardial effusions secondary to lung cancer. METHODS: In our clinic, three patients with recurrent pericardial effusion secondary to lung cancer were treated with percutaneous pericardiotomy with an Inoue valvuloplasty balloon catheter through the subxiphoid approach. RESULTS: Successful drainage with balloon pericardiotomy was achieved in all patients without severe complications. In all cases, only one pericardial site was dilated at least three times. During the four to six months of follow up, there were no recurrences of the effusion or tamponade. All patients were still alive. CONCLUSIONS: In our experience, PBP with the Inoue balloon appears to be a simple and safe procedure with a high success rate. PBP is an effective method for the management of patients with recurrent, large, malignant pericardial effusions. PMID- 24217125 TI - Acute ST-elevation myocardial infarction in early puerperium due to severe left main coronary stenosis in a woman with familial hyperlipidaemia. AB - Acute myocardial infarction (AMI) is a rare but often catastrophic event during pregnancy, delivery or puerperium, leading to a high mortality rate. It has different pathogenic mechanisms, such as atherosclerosis, vasospasm, thrombosis and coronary dissection. Although MI has been reported in pregnant women at all stages of pregnancy and postpartum, it occurs more commonly in the third trimester and most commonly involves the anterior wall. Evidence suggests that pregnancy itself is an independent risk factor for MI, conferring a three- to four-fold higher risk than that of nonpregnant women matched for age, possibly due to the unique physiological changes required to meet the demands of a growing foetus. We report a case of a 27-year-old woman with familial hyperlipidaemia presenting with myocardial infarction six days after caesarean delivery, secondary to severe left main coronary stenosis (LMCA), who was treated with emergency coronary artery bypass grafting (CABG). PMID- 24217126 TI - Acute myocardial infarction after prednisolone administration for the treatment of anaphylaxis caused by a wasp sting. AB - BACKGROUND: Wasp stings have been demonstrated to cause a wide spectrum of allergic reactions from localised reactions to anaphylaxis. Acute coronary syndromes have been described as potential complications of anaphylactic reactions or some of the drugs used for the treatment of anaphylaxis. We know of only a few cases reported of acute myocardial infarction (MI) following corticosteroid administration or anaphylaxis in subjects with normal coronary arteries. If it exists, underlying subclinical coronary atherosclerosis may become clinically evident. CASE REPORT: A 20 year-old male with anaphylaxis due to a wasp sting, complicated by acute ST-elevation MI after intravenous methyl prednisolone administration, is the subject of this report. He was admitted to our emergency service for dizziness, blurred vision, presyncope and mild respiratory distress 10 minutes after the wasp had stung him on the nape of the neck. Six to seven minutes after administration of prednisolone, the patient complained of typical chest pains. A high posterolateral MI with mild mitral regurgitation were seen on examination. He was treated conservatively with aspirin and heparine. Coronary angiography and intravascular ultrasound imaging, performed 10 days later, showed no evidence of obstructive coronary artery disease. CONCLUSION: Although reduced coronary perfusion, local histamine release induced coronary vasospasm or severe hypoxia have been suggested, the pathophysiology remains unclear. Acute STEMI may be a rare but clinically important complication of a wasp sting, anaphylaxis or the corticosteroid used for its treatment, even in young adults with normal coronary arteries. Therefore, physicians should be aware of such serious complications in order to diagnose them early. PMID- 24217127 TI - Delayed chylopericardium as a rare complication after combined mitral valve and coronary artery bypass surgery. AB - Chylopericardium is a rare complication of cardiac surgery that is performed from a midline sternotomy. Here we present a case of a 61-year-old male patient with late-onset postoperative chylopericardium following combined coronary artery bypass grafting and mitral valve surgery, and the applied treatment modality. PMID- 24217128 TI - Antibacterial activity of moxifloxacin on bacteria associated with periodontitis within a biofilm. AB - The activity of moxifloxacin was compared with ofloxacin and doxycycline against bacteria associated with periodontitis within a biofilm (single strain and mixed population) in vitro. MICs and minimal bactericidal concentrations (MBCs) of moxifloxacin, ofloxacin and doxycyline were determined against single strains and mixed populations in a planktonic state. Single-species biofilms of two Porphyromonas gingivalis and two Aggregatibacter actinomycetemcomitans strains and a multispecies biofilm consisting of 12 species were formed for 3 days. The minimal biofilm eradication concentrations (MBECs) were determined after exposing the biofilms to the antibacterials (0.002-512 ug ml(-1)) for 18 h, addition of nutrient broth for 3 days and subsequent subcultivation. Photographs were taken using confocal laser-scanning microscopy and scanning electron microscopy. The MICs and MBCs did not differ between ofloxacin and moxifloxacin against A. actinomycetemcomitans, whilst moxifloxacin was more active than the other tested antibacterials against anaerobes and the mixed population. The single-species biofilms were eradicated by moderate concentrations of the antibacterials, and the lowest MBECs were always found for moxifloxacin (2-8 ug ml(-1)). MBECs against the multispecies biofilms were 128, >512 and >512 ug ml(-1) for moxifloxacin, ofloxacin and doxycycline, respectively. In summary, moxifloxacin in a topical formulation may have potential as an adjunct to mechanical removal of the biofilms. PMID- 24217130 TI - Optical orbital angular momentum conservation during the transfer process from plasmonic vortex lens to light. AB - We demonstrate the optical orbital angular momentum conservation during the transfer process from subwavelength plasmonic vortex lens (PVLs) to light and the generating process of surface plasmon polaritons (SPPs). Illuminating plasmonic vortex lenses with beams carrying optical orbital angular momentum, the SP vortices with orbital angular momentum were generated and inherit the optical angular momentum of light beams and PVLs. The angular momentum of twisting SP electromagnetic field is tunable by the twisted metal/dielectric interfaces of PVLs and angular momentum of illuminating singular light. This work may open the door for several possible applications of SP vortices in subwavelength region. PMID- 24217129 TI - D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial. AB - Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD. PMID- 24217131 TI - Interplay between microstructure and magnetism in NiO nanoparticles: breakdown of the antiferromagnetic order. AB - The possibility of tuning the magnetic behaviour of nanostructured 3d transition metal oxides has opened up the path for extensive research activity in the nanoscale world. In this work we report on how the antiferromagnetism of a bulk material can be broken when reducing its size under a given threshold. We combined X-ray diffraction, high-resolution transmission electron microscopy, extended X-ray absorption fine structure and magnetic measurements in order to describe the influence of the microstructure and morphology on the magnetic behaviour of NiO nanoparticles (NPs) with sizes ranging from 2.5 to 9 nm. The present findings reveal that size effects induce surface spin frustration which competes with the expected antiferromagnetic (AFM) order, typical of bulk NiO, giving rise to a threshold size for the AFM phase to nucleate. Ni(2+) magnetic moments in 2.5 nm NPs seem to be in a spin glass (SG) state, whereas larger NPs are formed by an uncompensated AFM core with a net magnetic moment surrounded by a SG shell. The coupling at the core-shell interface leads to an exchange bias effect manifested at low temperature as horizontal shifts of the hysteresis loop (~1 kOe) and a coercivity enhancement (~0.2 kOe). PMID- 24217132 TI - Data-adapted moving least squares method for 3-D image interpolation. AB - In this paper, we present a nonlinear three-dimensional interpolation scheme for gray-level medical images. The scheme is based on the moving least squares method but introduces a fundamental modification. For a given evaluation point, the proposed method finds the local best approximation by reproducing polynomials of a certain degree. In particular, in order to obtain a better match to the local structures of the given image, we employ locally data-adapted least squares methods that can improve the classical one. Some numerical experiments are presented to demonstrate the performance of the proposed method. Five types of data sets are used: MR brain, MR foot, MR abdomen, CT head, and CT foot. From each of the five types, we choose five volumes. The scheme is compared with some well-known linear methods and other recently developed nonlinear methods. For quantitative comparison, we follow the paradigm proposed by Grevera and Udupa (1998). (Each slice is first assumed to be unknown then interpolated by each method. The performance of each interpolation method is assessed statistically.) The PSNR results for the estimated volumes are also provided. We observe that the new method generates better results in both quantitative and visual quality comparisons. PMID- 24217133 TI - A novel, rigid diphosphine with an active NHC spacer; di- and trinuclear complexes of d10 coinage metals. AB - A novel N,N'-diphosphanyl-imidazol-2-ylidene acts as a stable, hybrid PC(NHC)P ligand for M2 or linear M3 (M = Cu, Ag, Au) arrays with metallophilic interactions. PMID- 24217134 TI - Extracorporeal shock wave therapy in musculoskeletal disorders: a review. AB - Regenerative therapy is one of the most challenging and intriguing branches of modern medicine. Basic research has demonstrated the effectiveness of extracorporeal shockwaves (ESWT) in stimulating biological activities that involve intra-cell and cell-matrix interactions. These interactions are at the basis of the current clinical applications, and open the horizons to new applications in tissue regeneration. It is also feasible that shock waves could be used to treat various orthopaedic pathologies, removing the need for surgery. However, suitable translational studies need to be performed before ESWT can become a valid alternative to surgery. PMID- 24217135 TI - The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients. AB - OBJECTIVE: The presence of BRCA gene mutation and low expressions of BRCA proteins are associated with a greater sensitivity of tumor cells to ionizing radiation and to cytostatics damaging the DNA of the cells. The purpose of this study was to estimate the rate of adverse events in BRCA1/2-associated breast cancer patients receiving anthracycline-based chemotherapy compared to patients without mutation. The authors also compared radiotherapy toxicity in these 2 groups. METHODS: The analysis included 270 early-stage breast cancer patients treated between 2006 and 2012. All patients were examined for the presence of BRCA1/2 mutations. RESULTS: BRCA mutation was detected in 41 (15%) patients. Toxicity grade 3, especially nausea and vomiting, was observed more often in noncarriers (7 vs. 13%, p = 0.0008). Neutropenia was detected more frequently in patients with BRCA1/2 mutation (32 vs. 10%), but only after 1 cycle of chemotherapy (p = 0.0007). There was increased radiation toxicity in BRCA1/2 patients who underwent mastectomy and neoadjuvant chemotherapy (p = 0.016). CONCLUSIONS: BRCA1/2 mutation carriers seemed to be more at risk of neutropenia after the first cycle of the treatment. In terms of other side effects, there was a lack of increased toxicity in this group. Mastectomy and neoadjuvant chemotherapy were risk factors for radiation toxicity in mutation carriers. PMID- 24217136 TI - Do you want to see the tree? Ignore the forest: inhibitory control during local processing: a negative priming study of local-global processing. AB - The visual environment consists of global structures (e.g., a forest) made up of local parts (e.g., trees). When compound stimuli are presented (e.g., large global letters composed of arrangements of small local letters), the global unattended information slows responses to local targets. Using a negative priming paradigm, we investigated whether inhibition is required to process hierarchical stimuli when information at the local level is in conflict with the one at the global level. The results show that when local and global information is in conflict, global information must be inhibited to process local information, but that the reverse is not true. This finding has potential direct implications for brain models of visual recognition, by suggesting that when local information is conflicting with global information, inhibitory control reduces feedback activity from global information (e.g., inhibits the forest) which allows the visual system to process local information (e.g., to focus attention on a particular tree). PMID- 24217137 TI - Age-related differences in sequential modulations of poorer-strategy effects. AB - To determine how younger and older adults modulate execution of strategies across successive trials, we asked participants to accomplish a computational estimation task (i.e., provide approximate products to two-digit multiplication problems like 38 * 74). For each problem, they were cued to execute a better versus a poorer strategy. Their performance revealed sequential modulations of poorer strategy effects (i.e., longer solution times and larger error rates when asked to execute a poorer than a better strategy). That is, poorer-strategy effects were smaller on current problems after using a poorer strategy on preceding problems than after using a better strategy. Moreover, sequential modulations of these poorer-strategy effects were smaller in older than in younger adults, especially older adults with low-cognitive control skills (as measured by conflict adaptation effects in the Simon task). Our findings suggest that these sequential modulations may result from executive control mechanisms, the efficiency of which is known to decrease in older adults. These findings have important implications regarding mechanisms underlying strategy execution and aging effects on strategic variations. PMID- 24217138 TI - Impact of feedback on three phases of performance monitoring. AB - We investigated if certain phases of performance monitoring show differential sensitivity to external feedback and thus rely on distinct mechanisms. The phases of interest were: the error phase (FE), the phase of the correct response after errors (FEC), and the phase of correct responses following corrects (FCC). We tested accuracy and reaction time (RT) on 12 conditions of a continuous-choice response task; the 2-back task. External feedback was either presented or not in FE and FEC, and delivered on 0%, 20%, or 100% of FCC trials. The FCC20 was matched to FE and FEC in the number of sounds received so that we could investigate when external feedback was most valuable to the participants. We found that external feedback led to a reduction in accuracy when presented on all the correct responses. Moreover, RT was significantly reduced for FCC100, which in turn correlated with the accuracy reduction. Interestingly, the correct response after an error was particularly sensitive to external feedback since accuracy was reduced when external feedback was presented during this phase but not for FCC20. Notably, error-monitoring was not influenced by feedback-type. The results are in line with models suggesting that the internal error-monitoring system is sufficient in cognitively demanding tasks where performance is ~ 80%, as well as theories stipulating that external feedback directs attention away from the task. Our data highlight the first correct response after an error as particularly sensitive to external feedback, suggesting that important consolidation of response strategy takes place here. PMID- 24217139 TI - The inhibitory advantage in bilingual children revisited: myth or reality? AB - In recent decades several authors have suggested that bilinguals exhibit enhanced cognitive control as compared to monolinguals and some proposals suggest that this main difference between monolinguals and bilinguals is related to bilinguals' enhanced capacity of inhibiting irrelevant information. This has led to the proposal of the so-called bilingual advantage in inhibitory skills. However, recent studies have cast some doubt on the locus and generality of the alleged bilingual advantage in inhibitory skills. In the current study we investigated inhibitory skills in a large sample of 252 monolingual and 252 bilingual children who were carefully matched on a large number of indices. We tested their performance in a verbal Stroop task and in a nonverbal version of the same task (the number size-congruency task). Results were unequivocal and showed that bilingual and monolingual participants performed equally in these two tasks across all the indices or markers of inhibitory skills explored. Furthermore, the lack of differences between monolingual and bilingual children extended to all the age ranges tested and was not modulated by any of the independent factors investigated. In light of these results, we conclude that bilingual children do not exhibit any specific advantage in simple inhibitory tasks as compared to monolinguals. PMID- 24217140 TI - Age-related decline in emotional prosody discrimination: acoustic correlates. AB - It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing. PMID- 24217143 TI - Improving stroke education performance measures scores: the impact of a stroke nurse coordinator. AB - BACKGROUND: Stroke is a leading cause of death and adult disability worldwide. North Carolina is considered to be a part of an area of the United States called the "stroke belt." Education coupled with implementation of a program that promotes primary and secondary stroke prevention is paramount to support the reduction of stroke and improvement of stroke care across the continuum. The groundwork for stroke care at Onslow Memorial Hospital began in 2006 with participation in the North Carolina Stroke Care Collaborative (NCSCC), which allowed for benchmarking of data. METHODS: A pretest and posttest design was used to evaluate the effectiveness of a dedicated stroke nurse coordinator on stroke education performance measure scores. Compliance with stroke education performance measures is met when documentation reflects education provided or material given during the hospital stay. Three hundred sixty-seven charts submitted to the NCSCC from Onslow Memorial Hospital were reviewed. Data collected were entered into the NCSCC Registry database during the period of 2008 2010. Performance measures were compared at three points: the year before implementation of the stroke nurse coordinator, the implementation year, and, the year after the implementation of the stroke nurse coordinator position. RESULTS: Stroke education performance measure scores for the preimplementation year (2008) were 58.1%, which improved to 86.4% for the year that the nurse coordinator position was created and filled, and rose to 96.9% for the 1-year period after the position was filled. Scores from Z tests comparing proportions over time between each of the 3 years were statistically significant. CONCLUSIONS: Implementation of a stroke nurse coordinator to improve stroke care and education is a coordinated effort that will impact stroke outcomes across the healthcare continuum, with efforts geared toward primary and secondary prevention strategies. This role provides supportive resources for the community, individualized care with patients and families as well as supporting staff in providing stroke education, and awareness. Stroke education has shown improvement in patients understanding the signs and symptoms of stroke as well as improved compliance with treatment plans; the use of a dedicated educator is supported. PMID- 24217142 TI - The stroke caregiver unmet resource needs scale: development and psychometric testing. AB - The purposes of this study were to develop and validate a measure of unmet resource needs of the caregivers of survivors of stroke and to describe the caregivers' unmet needs during 1 year. A longitudinal, descriptive design was used to test the reliability and validity of the Unmet Resource Needs (URN) measure. Item development was based on literature review and preliminary study findings. A stress and coping conceptual model framed the hypotheses. Psychometric testing was based on 6-month postdischarge data (n = 166). Content and structural construct validity, internal consistency reliability through 1 year, and concurrent validity were tested. Change in URN over time was examined. Content validity was supported by floor and ceiling effects less than 5%. Principal axis factoring yielded a 12-item, two-factor solution reflecting general and technology unmet needs. Internal consistency reliability was satisfactory for the total scale and subscales at all times, excepting the baseline three-item technology scale (alpha = .56). Concurrent validity was supported by significant correlations with model constructs (threat, positive problem solving, depression, preparedness; p < .01) in the expected direction. Functional status and resource use were not associated with the URN. Repeated measures analysis of variance (n = 123) indicated a significant decrease in unmet needs from baseline to 3, 6, and 12 months postdischarge (p < .001). Nevertheless, 42% reported one or more unmet needs at year 1. Assessment and counseling on unmet needs is indicated throughout the caregiving trajectory to reduce negative outcomes. PMID- 24217144 TI - Information availability for a patient with stroke in an emergency department: a training intervention study. AB - The purpose of the study is to describe the information availability for patients with stroke treated in an emergency department and to study the effects of intervention training on this information availability. The material was collected from two university hospitals with a structured survey both before the training (n = 190, 2006-2007) and after the training (n = 170, 2007-2008). The study indicated that patients with stroke felt that the information availability was good on average. The patients felt that they were best informed about tests and their treatment and worst informed about symptoms and instructions. The following background factors affected their perception of information availability: waiting time, age of the patient, and previous hospital experience. Effective intervention training needs to be further developed to enhance information availability. Training should be carried out systematically and should consist of both basic and ongoing training, and the content should be developed in collaboration with patients with stroke. PMID- 24217145 TI - Dementia with Lewy bodies: a comprehensive review for nurses. AB - Much of the current nursing literature on dementia focuses on Alzheimer disease (AD), the dementia subtype most commonly diagnosed in the older adults. There is a paucity of nursing literature on dementia with Lewy bodies (DLB), the second most common subtype of dementia, which is closely associated with Parkinson disease with dementia (PDD), considered the third most common dementia subtype. Both are aging-related disorders attributed to Lewy bodies, abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset. Although basic science knowledge of DLB has increased exponentially, the lack of nursing research on DLB indicates that this knowledge excludes the nursing perspective and its implications for nursing practice. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with PDD and Alzheimer disease and to propose key nursing interventions for clinical practice. PMID- 24217146 TI - Monitoring and sedation differences in the management of severe head injury and subarachnoid hemorrhage among neurocritical care centers. AB - BACKGROUND: The emergence of specialized neurocritical care (NCC) centers has been associated with an improved survival of patients with severe traumatic brain injury or subarachnoid hemorrhage. However, there are no established guidelines on sedation strategy or the frequency of evaluating the level of consciousness using the neurological wake-up test (NWT) in sedated NCC patients. OBJECTIVES: The aim was to compare the (1) monitoring techniques, (2) sedation principles, and (3) the use of the NWT in patients with severe traumatic brain injury or subarachnoid hemorrhage in 16 NCC centers. METHOD: A systematic survey of all 16 centers providing NCC in Scandinavia was performed using a questionnaire regarding the routine primary choice of sedative and analgesic compounds, monitoring techniques, and the frequency of the NWT, sent to the director of each center during 1999, 2004, and 2009. RESULTS: The response rate was 100%. Except for one center in 1999, all included centers routinely used monitoring of intracranial and cerebral perfusion pressure. In contrast, newer monitoring techniques such as microdialysis, jugular bulb oximetry, and brain tissue oxygenation were infrequently used throughout the survey period. Approximately half of the NCC centers used propofol infusion as the primary sedative, whereas the remaining centers used midazolam infusion, and there was a marked variation in the choice of analgesia in each evaluated year. The NWT was never used in 50% of centers and >=six times daily in one center from 1999 to 2009. Most differences among the NCC centers remained unchanged over the evaluated 10-year period. DISCUSSION: Although Scandinavian countries have similar healthcare systems, there were marked differences among the participating NCC centers in the choice of monitoring tools and sedatives and the routine use of the NWT. These differences likely reflect different clinical management traditions and a lack of evidence-based guidelines in routine NCC. PMID- 24217147 TI - The experiences of Taiwanese older individuals at different stages of Parkinson disease. AB - Parkinson disease (PD) is a progressive neurological condition, usually occurring among older individuals. Along with increasing handicaps in daily life, patients with PD also face problems with psychosocial adjustment. This study explored the experiences of older Taiwanese individuals at different stages of PD. Qualitative design with in-depth interviews was conducted with participants being treated at the neurology outpatient department in a teaching hospital in northern Taiwan. The study included nine men and six women, aged 65-80 years, with PD at stages 1 4. Comparative analysis of the interviews revealed four themes: ignorance of symptoms, loss of control, gradual deterioration, and a deep sense of helplessness. In stage 1, symptoms were not significant at the onset of PD. For most participants, others first detected the symptoms, rather than themselves. During stage 2, although they could still care for themselves, they became very anxious when the effects of medication disappeared and their reactions slowed before they took the next dose. During stage 3, the physical capacity of the body decreased gradually and affected the patient's participation in social activities. In stage 4, older patients gradually became dependent on others in their daily lives. They were upset and worried that the symptoms would worsen and make them become a burden for their children. By understanding the perceptions of elderly patients at different stages of PD, this study has organized the key care requirements into four stages. These include the following: (1) provide more information on the disease in stage 1, (2) increase guidance on regular medication usage and establish a support system in stage 2, (3) highlight the importance of a safe living environment and encourage participation in support groups in stage 3, and (4) assist patients to find the meaning of life and value of existence in stage 4. PMID- 24217148 TI - The impact of restless legs syndrome: a familial case study. AB - Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move. RLS has a general population incidence of between 5% and 10% and a familial rate as high as 77%. This case study examines the pathophysiology, diagnosis, and treatment along with the presentation of RLS in two members of a family with near-identical onset and treatment. Cases of familial RLS may be best directed toward similar treatment regimens. PMID- 24217149 TI - Lower urinary tract symptoms in men with Parkinson disease. AB - PURPOSE: The aim of this study was to examine the prevalence, presentation, and predictors of lower urinary tract symptoms (LUTS) in men with idiopathic Parkinson disease (PD). METHODS: Guided by the Theory of Unpleasant Symptoms, this retrospective exploratory study used data abstracted from admission clinical records of 271 male patients with idiopathic PD enrolled in a movement disorders clinic at a large metropolitan Veterans Affairs Medical Center in the eastern region of the United States. Data from the admission questionnaire, Unified Parkinson's Disease Rating Scale, and Mini Mental State Examination were abstracted by trained research assistants. Interrater reliability for the abstraction process was 0.99 in a randomly selected 10% sample of records. Descriptive statistics were used to determine the prevalence of LUTS. Logistic regression was used to determine LUTS risk factors and predictors. RESULTS: At least one LUTS was reported by 40.2% of participants. Incontinence was the most prevalent symptom, affecting almost 25% of participants, followed by nocturia (14.8%) and frequency (13.7%). Of the 10 identified risk factors for LUTS, four significant predictors were discovered: number of non-PD medications (p < .05), PD duration (p < .05), number of comorbidities (p < .05), and history of a hernia diagnosis (p < .05). CONCLUSIONS: Assessment for LUTS should be a component of every evaluation of a patient with PD. Our findings offer a preliminary profile of the male PD patient with LUTS, which is an important step toward effective screening, detection, and access to care and treatment. Next steps in research include further work to identify predictors of LUTS in both male and female PD populations, explore patient perspectives, begin trials of interventions for LUTS in the PD population, and analyze the economic impact. PMID- 24217152 TI - Spaceflight and ageing: reflecting on Caenorhabditis elegans in space. AB - The prospect of space travel continues to capture the imagination. Several competing companies are now promising flights for the general population. Previously, it was recognized that many of the physiological changes that occur with spaceflight are similar to those seen with normal ageing. This led to the notion that spaceflight can be used as a model of accelerated ageing and raised concerns about the safety of individuals engaging in space travel. Paradoxically, however, space travel has been recently shown to be beneficial to some aspects of muscle health in the tiny worm Caenorhabditis elegans. C. elegans is a commonly used laboratory animal for studying ageing. C. elegans displays age-related decline of some biological processes observed in ageing humans, and about 35% of C. elegans' genes have human homologs. Space flown worms were found to have decreased expression of a number of genes that increase lifespan when expressed at lower levels. These changes were accompanied by decreased accumulation of toxic protein aggregates in ageing worms' muscles. Thus, in addition to spaceflight producing physiological changes that are similar to accelerated ageing, it also appears to produce some changes similar to delayed ageing. Here, we put forward the hypothesis that in addition to the previously well-appreciated mechanotransduction changes, neural and endocrine signals are altered in response to spaceflight and that these may have both negative (e.g. less muscle protein) and some positive consequences (e.g. healthier muscles), at least for invertebrates, with respect to health in space. Given that changes in circulating hormones are well documented with age and in astronauts, our view is that further research into the relationship between metabolic control, ageing, and adaptation to the environment should be productive in advancing our understanding of the physiology of both spaceflight and ageing. PMID- 24217151 TI - Comparison of the possible protective effect of the salivary pellicle of individuals with and without erosion. AB - The acquired pellicle adheres to tooth surfaces and has been suggested to provide differing degrees of protection against acidic erosion. This study investigated whether pellicle formed on enamel blocks in patients suffering dietary dental erosion modified the effect of an in vitro simulated dietary challenge, in comparison with pellicle formed on enamel blocks in healthy subjects and to no pellicle enamel samples. Sixty subjects recruited from dental erosion clinics were compared to healthy age-matched controls. Subjects wore a custom-made maxillary splint holding human enamel blocks for 1 h during which the acquired enamel pellicle was formed. Enamel blocks were removed from the splints and a simulated dietary erosive challenge of 10 min was performed. In addition the challenge was performed on 30 enamel samples without pellicle. Profilometry showed no statistical difference between samples from the erosion subjects with a mean step height of 1.74 um (SD 0.88) and median roughness (Sa) of 0.39 um (interquartile range, IQR 0.3-0.56) and the controls with 1.34 um (SD 0.66) and 0.33 um (IQR 0.27-0.38), respectively. The control samples without pellicle had Sa of 0.44 um (IQR 0.36-0.69) and these differences were statistically significant compared to those from the healthy subjects (p = 0.002). Mean (SD) microhardness reduction with a 100-gram load for the erosion group was 113.5 (10) KHN, for healthy subjects was 93 (15.4) KHN and for the enamel samples without pellicle 139.6 (21.8) KHN and all groups were statistically different. The microhardness and roughness data suggested the pellicle influenced erosion under these study conditions. PMID- 24217153 TI - Single-institution retrospective series of gamma knife radiosurgery in the treatment of multiple sclerosis-related trigeminal neuralgia: factors that predict efficacy. AB - BACKGROUND: Gamma knife radiosurgery (GKRS) has been reported as a treatment option for multiple sclerosis (MS)-related trigeminal neuralgia. OBJECTIVE: To report the outcomes of a single-institution retrospective series of MS-related trigeminal neuralgia. METHODS: Between 2002 and 2010, 35 patients with MS-related trigeminal neuralgia were treated with GKRS. The median maximum dose was 90 Gy. Data were analyzed to determine the response to GKRS and factors that may predict for efficacy. RESULTS: Of the 35 patients, 88% experienced a Barrow Neurological Institute (BNI) pain score of I-III at 3 months after GKRS. Kaplan-Meier estimates of 1-, 2- and 5-year freedom from BNI IV-V pain relapse were 57, 57 and 52%, respectively. Numbness was experienced by 39% of patients after GKRS, though no patients reported bothersome numbness. Several differences were noted between how the MS-related variant responded to GKRS and what has previously been reported for idiopathic trigeminal neuralgia. These include the observations that development of post-GKRS numbness did not predict for treatment response (p = 0.62) and that dorsal root entry zone dose did not predict for freedom from pain relapse (odds ratio 1.01, p = 0.1). Active smoking predicted for freedom from pain relapse (odds ratio 67.4, p = 0.04). CONCLUSION: GKRS is a viable noninvasive treatment option for MS-related trigeminal neuralgia. PMID- 24217154 TI - The tumor suppressor axis p53/miR-34a regulates Axl expression in B-cell chronic lymphocytic leukemia: implications for therapy in p53-defective CLL patients. PMID- 24217155 TI - Do women with pain and bleeding in early pregnancy require a vaginal speculum examination as part of their assessment? AB - AIMS: To investigate whether a vaginal speculum examination (VSE) prior to a transvaginal scan (TVS) alters the diagnosis or management of women who complain of bleeding in early pregnancy. METHODS: A prospective study. Women were asked to describe their bleeding as heavy, moderate or light and to consent to VSE prior to TVS. TVS was performed to obtain a final diagnosis of pregnancy outcome. RESULTS: 221 consecutive women were included in the study. In 14.5% (n = 32) complaining of heavy bleeding, blood was seen in all but two VSE and 84% (n = 27) had a miscarriage diagnosed by TVS. Products of conception were removed in 18.8% (n = 6), but this did not alter the subsequent immediate management of any cases. 65.2% (n = 144) of women complained of light bleeding, blood was seen on VSE in 53% (n = 77). Of these women, 25% (n = 19) of those where blood was seen had a miscarriage, compared to 6% (n = 4) of women where blood was not seen. A cervical ectropion was visualised in 11.7% (n = 26) and 2.3% (n = 5) had a cervical polyp. No other clinically significant pathology was detected. CONCLUSION: The amount of bleeding reported by women in early pregnancy relates well with VSE findings. Performing a VSE did not alter the subsequent management of these patients. This study demonstrates that routine objective assessment of blood by a clinician performing VSE prior to a TVS is unnecessary. PMID- 24217156 TI - Quasi free-standing silicene in a superlattice with hexagonal boron nitride. AB - We study a superlattice of silicene and hexagonal boron nitride by first principles calculations and demonstrate that the interaction between the layers of the superlattice is very small. As a consequence, quasi free-standing silicene is realized in this superlattice. In particular, the Dirac cone of silicene is preserved. Due to the wide band gap of hexagonal boron nitride, the superlattice realizes the characteristic physical phenomena of free-standing silicene. In particular, we address by model calculations the combined effect of the intrinsic spin-orbit coupling and an external electric field, which induces a transition from a semimetal to a topological insulator and further to a band insulator. PMID- 24217157 TI - Interventional cardiology: ischaemic POSTconditioning-a long harvest for a little corn. PMID- 24217159 TI - Beyond anti-PCSK9 therapies: the potential role of resistin inhibitors. PMID- 24217158 TI - So hard to say goodbye: transition from paediatric to adult cardiology care. AB - Important medical advances have created a large and growing population of adults who were diagnosed with congenital or paediatric-onset cardiovascular conditions as children and now require specialized cardiac care as adults. Although some adult patients continue to be cared for by paediatric cardiology programmes, guidelines recommend that patients transfer from paediatric to adult care at 18 21 years of age. Unfortunately, lapses in care during the transfer period are common and associated with poor health outcomes. Comprehensive transition programmes are necessary to maintain continuity of care and effectively prepare adolescents and young adults for the differences between paediatric and adult cardiac care programmes. Transition, unlike transfer, is an extended process that begins during childhood or early adolescence and focuses on patient education and fostering self-management skills and appropriate interdependence. The perspectives of patients, families, and care providers should be recognized and incorporated into transition programmes, and should be used to adapt strategies to meet the needs of individual patients and families. This Review summarizes the current knowledge on the transition of young patients from paediatric to adult cardiology care from the perspectives of all stakeholders, and offers practical recommendations for the development of transition programmes. PMID- 24217160 TI - The Pan-African Society of Cardiology (PASCAR) in 2013 and beyond. AB - The biennial Congress of the Pan-African Society of Cardiology (PASCAR) was held in Dakar from 16 to 19 May 2013 under the patronage of his Excellency, Macky Sall, president of the Republic of Senegal. This meeting was remarkable in the diversity of its 700 participants from English-, French- and Portuguese-speaking Africa. Important aspects of cardiovascular disease in Africa were presented in 195 abstracts and numerous talks; the topics were hypertension, obesity, diabetes, heart failure, cardiomyopathies, coronary heart disease, stroke and rheumatic heart disease. The general assembly meeting was marked by the review and adoption of a new constitution and elections of a new PASCAR governing council that will be in office for the next four years. The new leadership of PASCAR has committed itself to strengthening the administrative infrastructure of the organisation, developing programmes to address education and training needs of African cardiovascular practitioners, developing a pan-African multi-national research platform, and ensuring that ministries of health implement national programmes for the prevention and control of cardiovascular and other noncommunicable diseases. PMID- 24217161 TI - Comparison of left atrial function in healthy individuals versus patients with non-ST-segment elevation myocardial infarction using two-dimensional speckle tracking echocardiography. AB - Left atrial (LA) function has been associated with adverse outcomes in patients after acute myocardial infarction. The purpose of the current study was to evaluate LA function in patients with non-ST-segment elevation myocardial infarction (NSTEMI) by two-dimensional speckle tracking echocardiography (2D STE). Fifty-one patients with NSTEMI and 40 age-matched normal control individuals were enrolled in this study. Conventional echocardiographic parameters and global longitudinal strain rate (GLSR) were measured at left ventricular (LV) and LA segments. Compared with healthy subjects, patients with NSTEMI had significantly increased LA volumes but significantly decreased LA emptying fraction and GLSR. LA-GLSR had significant correlations with the 2D Doppler echocardiographic parameters of LA function. In particular, global LA peak negative strain rate during early ventricular diastole (LA-GLSRe) was significantly correlated with both LA 2D Doppler echocardiographic parameters and LV contractile function. This could be suggested as a better indicator to evaluate LA function as a preferred parameter of STE. PMID- 24217162 TI - A comparison between size of the occluder device and two-dimensional transoesophageal echocardiographic sizing of the ostium secundum atrial septal defect. AB - OBJECTIVES: Transcatheter closure of a secundum atrial septal defect (ASD II) has become an effective alternative for surgical treatment. In this study we evaluated the correlation between the two-dimensional transoesophageal echocardiographic (2D TEE) sizing of ASDs and the actual diameter of occluders in patients undergoing device closure. METHODS: The records of 54 patients who underwent transcatheter ASD closure were reviewed. ASD characteristics and maximum defect diameter were evaluated using preprocedure 2D TEE images. Appropriate device size was determined by the balloon sizing method, which measures the balloon occlusive diameter (BOD) via TEE and fluoroscopy. ASD closure was performed under continuous TEE monitoring using the Amplatzer occluder in all patients. RESULTS: The mean of the TEE-derived maximum defect diameter was significantly lower than the mean of the BOD (17.8 +/- 4.5 vs 22.1 +/- 5.1 mm; p < 0.001) and the mean size of the implanted occluder device (17.8 +/- 4.5 vs 23.3 +/- 5.1 mm; p < 0.001). However, a good correlation was found between the TEE-derived defect size and the BOD (BOD = 0.898 * TEE defect size + 6.212, R = 0.824; p < 0.001) and between the TEE measurement and the final size of the implanted Amplatzer (device size = 0.928 * TEE defect size + 6.853, R = 0.822; p < 0.001). CONCLUSION: 2D TEE may provide a good equation to predict the BOD or the size of the occluder device; however, further studies are needed to investigate whether it is feasible to perform transcatheter ASD occlusion without balloon sizing. PMID- 24217163 TI - The optimal time of B-type natriuretic peptide sampling associated with post myocardial infarction remodelling after primary percutaneous coronary intervention. AB - AIMS: To find the optimal time to evaluate plasma B-type natriuretic peptide (BNP), which is related to post-myocardial infarction remodelling (PMIR), we measured serial plasma BNP levels according to time protocols after primary percutaneous coronary intervention (PCI). BACKGROUND: It has been established that plasma BNP levels can predict the development of PMIR in patients with ST elevation myocardial infarction (STEMI). However, the time of plasma BNP sampling associated with PMIR is still controversial. METHODS: We analysed 42 patients who were diagnosed as PMIR on six-month follow-up echocardiography among 131 patients with STEMI. We then compared clinical variables including plasma BNP between the remodelling group and the non-remodelling group. The plasma BNP level was obtained on hospital admission (acute phase), at two to five days (early phase), three to four weeks (late phase) and at the six-month follow up (long term). RESULTS: Early-phase and long-term BNP levels were higher in the remodelling group. The serial plasma BNP levels, according to study protocols, showed a biphasic pattern of elevation. In multiple logistic regression analyses, early phase BNP [odds ratio (OR): 1.013, p < 0.01] and acute-phase BNP levels (OR: 1.007, p = 0.02) were independent predictors of PMIR. However, early-phase BNP level was statistically a more powerful predictor of PMIR during follow up. CONCLUSION: Consecutive BNP levels after primary PCI showed a biphasic peak elevation during follow up. Early-phase plasma BNP level was an independent predictor of PMIR in patients with STEMI. PMID- 24217164 TI - Epidemiological and clinical features, ultrasound findings and prognosis of right sided infective endocarditis in a teaching hospital in Ouagadougou. AB - INTRODUCTION: Right-sided infective endocarditis is rare. It accounts about 5 to 10% of all infective endocarditis cases and is prevalent in patients with congenital heart disease, intravascular devices and drug addiction. Our study aimed to describe the epidemiological, clinical and echocardiographic characteristics of right-sided endocarditis and evaluate the prognosis after treatment. METHODS: From January 2010 to December 2011 we recruited all patients admitted to Yalgado Ouedraogo Teaching Hospital for infective endocarditis, and selected those who had a right-sided location. The Duke criteria were used for diagnosis. We analysed entry points and underlying heart disease. The causative organisms were tracked using blood sample cultures. Ultrasound characteristics were described, and treatment and prognosis were evaluated. Patients' follow up was conducted from recruitment to 30 June 2012. RESULTS: In the two-year period, 14 cases of right-sided infective endocarditis were recorded, including seven cases in children. They accounted for 29.1% of all infective endocarditis cases. The mean age was 25.5 +/- 12.5 years (range 9-80 years). The venous route was implicated in 12 cases (85.7%). Blood cultures were positive in 11 patients. The bacteria isolated were Streptococcus pneumonia in six cases, Staphylococcus aureus in three and Hemophilus influenza in two cases. HIV status was positive in three patients. Underlying heart diseases were dominated by congenital heart disease in six cases and peripartal cardiomyopathy in four others. Vegetations were located in the right heart in only 11 cases. With antibiotic treatment, a lowering of temperature was shown within an average of 10 days of follow up. Two fatalities were reported. CONCLUSION: This study showed that right-sided endocarditis is common in our clinical practice. This infection was prevalent in patients with congenital heart disease or peripartal cardiomyopathy in our context, and the venous route seemed to be the main entry point. PMID- 24217165 TI - Prevalence and determinants of hypertension and associated cardiovascular risk factors: data from a population-based, cross-sectional survey in Saint Louis, Senegal. AB - BACKGROUND: The incidence of cardiovascular disease is growing worldwide and this is of major public health concern. In sub-Saharan Africa, there is a lack of epidemiological data on the prevalence and distribution of risk factors of cardiovascular disease. This study aimed at assessing the prevalence of hypertension and other cardiovascular risk factors among an urban Senegalese population. METHODS: Using an adaptation of the WHO STEPwise approach to chronic disease risk-factor surveillance, we conducted a population-based, cross sectional survey from 3 to 30 May 2010 on 1 424 participants aged over 15 years. Socio-demographic and behavioural risk factors were collected in step 1. Physical anthropometryc measurements and blood pressure were documented in step 2. Blood tests (cholesterol, fasting blood glucose, and creatinine levels) were carried out in step 3. RESULTS: The prevalence of hypertension was 46% (95% CI: 43.4 48%), with a higher prevalence in females (47.9%) than males (41.7%) (p = 0.015), and 50% of these hypertensive were previously undiagnosed. Mean age was 53.6 years (SD: 15.8). In known cases of hypertension, the average length of its evolution was 6 years 9 months (range 1 month to 60 years). Hypertension was significantly associated with age (p = 0.001), socio-professional category (p = 0.003), dyslipidaemia (p < 0.001), obesity (p < 0.001), physical inactivity (p < 0.001), diabetes (p < 0.001) and stroke (p < 0.001). CONCLUSION: We found a high prevalence of hypertension and other cardiovascular risk factors in this population. There is need of a specific programme for the management and prevention of cardiovascular disease in this population. PMID- 24217166 TI - Pre-treatment before coronary artery bypass surgery improves post-operative outcomes in moderate chronic obstructive pulmonary disease patients. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has traditionally been recognised as a predictor of poorer early outcomes in patients undergoing coronary artery bypass grafting (CABG). The aim of this study was to analyse the impact of different COPD stages, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric criteria, on the early surgical outcomes in patients undergoing primary isolated non-emergency CABG. METHOD: Between January 2008 and April 2012, 1 737 consecutive patients underwent isolated CABG in the Department of Cardiovascular Surgery of Gulhane Military Academy of Medicine; 127 patients with the diagnosis of moderate-risk COPD were operated on. Only 104 patients with available pulmonary function tests and no missing data were included in the study. Two different treatment protocols had been used before and after 2010. Before 2010, no treatment was applied to patients with moderate COPD before the CABG procedure. After 2010, a pre treatment protocol was initiated. Patients who had undergone surgery between 2008 and 2010 were placed in group 1 (no pre-treatment, n = 51) and patients who had undergone surgery between 2010 and 2012 comprised group 2 (pre-treatment group, n = 53). These two groups were compared according to the postoperative morbidity and mortality rates retrospectively, from medical reports. RESULTS: The mean ages of the patients in both groups were 62.1 +/- 7.6 and 64.5 +/- 6.4 years, respectively. Thirty-nine of the patients in group 1 and 38 in group 2 were male. There were similar numbers of risk factors such as diabetes, hypertension, renal disease (two patients in each group), previous stroke and myocardial infarction in both groups. The mean ejection fractions of the patients were 53.3 +/- 11.5% and 50.2 +/- 10.8%, respectively. Mean EuroSCOREs of the patients were 5.5 +/- 2.3 and 5.9 +/- 2.5, respectively in the groups. The average numbers of the grafts were 3.1 +/- 1.0 and 2.9 +/- 0.9. Mean extubation times were 8.52 +/- 1.3 hours in group 1 and 6.34 +/- 1.0 hours in group 2. The numbers of patients who needed pharmacological inotropic support were 12 in group 1 and five in group 2. Duration of hospital stay of the patients was shorter in group 2. While there were 14 patients with post-operative atrial fibrillation (PAF) in group 1, the number of patients with PAF in group 2 was five. Whereas there were seven patients who had pleural effusions requiring drainage in group 1, there were only two in group 2. There were three mortalities in group 1, and one in group 2. There were no sternal infections and sternal dehiscences in either group. CONCLUSION: Pre-treatment in moderate-risk COPD patients improved post-operative outcomes while decreasing adverse events and complications. Therefore for patients undergoing elective CABG, we recommend the use of medical treatment. PMID- 24217167 TI - Isolated left ventricular non-compaction in Africa: elucidating myths. PMID- 24217169 TI - 4th All-African conference on heart disease, diabetes and stroke 11th Pan-African Society of Cardiology (PASCAR) conference. PMID- 24217168 TI - Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology. AB - The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology. PMID- 24217170 TI - Maternal imbalance between pro-angiogenic and anti-angiogenic factors in HIV infected women with pre-eclampsia. AB - Angiogenic imbalance contributes to the development of preeclampsia. We evaluated the protein expression of the proangiogenic placental growth factor (PlGF) and transforming growth factor beta 1 (TGF-beta1) compared with the anti-angiogenic soluble fms-like tyrosine kinase receptor (sFlt1) and soluble endoglin (sEng) in HIV-infected normotensive and pre-eclamptic pregnancies. Blood was obtained from 110 pregnant women, enrolled in four groups, namely, HIV-negative normotensives (27); HIV-positive normotensives (31); HIV-negative pre-eclamptics (27) and HIV positive pre-eclamptics (25), and was used to measure PlGF, TGF-beta1, sFlt1 and sEng levels. Increased sFlt1 and sEng levels were associated with the pre eclamptics (HIV negative and positive) compared with their counterparts. Decreased PlGF levels were observed between the HIV-negative pre-eclamptics versus HIV-negative normotensives, but levels differed significantly (p = 0.02) among the normotensives (HIV negative and positive). TGF-beta1 remained unchanged across all groups. Higher sEng/TGF-beta1 ratios were associated with the pre eclamptics (HIV negative and positive) compared with their counterparts. This study demonstrated increased sFlt1 and sEng levels in pre-eclamptic compared with normotensive pregnancies, irrespective of the HIV status. PMID- 24217172 TI - Biocompatible macro-initiators controlling radical retention in microfluidic on chip photo-polymerization of water-in-oil emulsions. AB - A series of water-soluble macro-initiators is synthesized to avoid radical loss in microfluidic on-chip photo cross-linking of hyaluronic acid methacrylate containing water-in-oil emulsions. Their superior performance over known photo initiators through the generation of water-soluble radicals and excellent biocompatibility are demonstrated. PMID- 24217173 TI - Fluorographene nanosheets with broad solvent dispersibility and their applications as a modified layer in organic field-effect transistors. AB - As the youngest in the graphene family, fluorographene has received numerous expectations from the scientific community. Investigation of fluorographene is similar to graphene and graphene oxide, wherein fabrication is an importance subject in the infancy stage. Fluorographene produced by the currently existing protocols, however, could only disperse in a limited number of solvents, and the dispersions generally exhibit short-term stability, restricting its manipulation and processing. To address this formidable challenge, we herein report that fluorographene nanosheets, most of which have a single-layered structure, could be easily formulated from commercially available graphite fluoride via a one-pot chloroform-mediated sonochemical exfoliation under ambient conditions without any pretreatment, special protection or stabilizers. Significantly, owing to the exceptional volatility of chloroform, our fluorographene originally dispersed in chloroform, could be facilely transferred into other 24 kinds of solvents via a volatilization-redispersion process, wherein dispersions of extremely long-term stability (more than six months) could be obtained. As an example to demonstrate the merit of the as-formulated fluorographene and its potential application possibilities, we further show that our fluorographene could be easily assembled as a modified layer in pentacene-based organic field-effect transistors simply by a spin-coating method, wherein distinctly increased mobility and positively shifted threshold voltage could be achieved. Considering the excellent popularity of chloroform in the scientific community, the remarkable volatility of chloroform, the broad solvent dispersibility of our fluorographene, and together with the long-term stability of the dispersions, our chloroform-mediated sonochemical exfoliation protocol likely endow fluorographene with new and broad opportunities for fabrication of graphene-based advanced functional films and nanocomposites via liquid-phase manipulation or solution-processing strategies. PMID- 24217171 TI - Amyloid imaging with carbon 11-labeled Pittsburgh compound B for traumatic brain injury. AB - OBJECTIVES: To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue. DESIGN, SETTING, AND PARTICIPANTS: In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for beta-amyloid (Abeta) and beta-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes. MAIN OUTCOMES AND MEASURES: We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Abeta and beta-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue. RESULTS: Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Abeta and beta-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels. CONCLUSIONS AND RELEVANCE: [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI. PMID- 24217174 TI - Facile synthesis of superparamagnetic mesoporous zeolite microspheres for the capacious enrichment of enzymes and proteins. AB - Superparamagnetic mesoporous zeolite microspheres with a large mesopore size of 13 nm and a high surface area of 382 m(2) g(-1) were synthesized for the capacious enrichment of proteins and enzymes. A high degree of ovalbumin immobilization was obtained (491 mg g(-1)) at pH 6, which is nearly twice that previously reported in the literature. PMID- 24217175 TI - Pore-forming pyocin S5 utilizes the FptA ferripyochelin receptor to kill Pseudomonas aeruginosa. AB - Pyocins are toxic proteins produced by some strains of Pseudomonas aeruginosa that are lethal for related strains of the same species. Some soluble pyocins (S2, S3 and S4) were previously shown to use the pyoverdine siderophore receptors to enter the cell. The P. aeruginosa PAO1 pore-forming pyocin S5 encoding gene (PAO985) was cloned into the expression vector pET15b, and the affinity-purified protein product tested for its killing activity against different P. aeruginosa strains. The results, however, did not show any correlation with a specific ferripyoverdine receptor. To further identify the S5 receptor, transposon mutants were generated. Pooled mutants were exposed to pyocin S5 and the resistant colonies growing in the killing zone were selected. The majority of S5-resistant mutants had an insertion in the fptA gene encoding the receptor for the siderophore pyochelin. Complementation of an fptA transposon mutant with the P. aeruginosa fptA gene in trans restored the sensitivity to S5. In order to define the receptor-binding domain of pyocin S5, two hybrid pyocins were constructed containing different regions from pyocin S5 fused to the C-terminal translocation and DNase killing domains of pyocin S2. Only the protein containing amino acid residues 151 to 300 from S5 showed toxicity, indicating that the pyocin S5 receptor-binding domain is not at the N-terminus of the protein as in other S type pyocins. Pyocin S5 was, however, unable to kill Burkholderia cenocepacia strains producing a ferripyochelin FptA receptor, nor was the B. cenocepacia fptA gene able to restore the sensitivity of the resistant fptA mutant P. aeruginosa strain. PMID- 24217176 TI - Compliance with mineral metabolism targets in haemodialysis patients: moving backwards? AB - BACKGROUND: To standardize therapy and improve the clinical outcome for chronic haemodialysis (HD) patients, guidelines have been developed for mineral metabolism management. We evaluated compliance with different mineral metabolism guidelines. METHODS: 2,951 chronic HD patients from 61 dialysis centres in Spain were studied. Mineral metabolism management data from a 1-year period were analysed according to KDOQI, KDIGO, and Spanish guidelines. RESULTS: Only 1% (KDOQI), 6% (KDIGO) and 11% (Spanish guidelines) of patients continuously achieved total calcium (Ca), phosphate (P) and parathyroid hormone (PTH) target range values during the year with higher percentages if we considered the 1-year average. The yearly Ca, P and iPTH average accomplished Spanish guidelines with different percentage among centres: CA 62-100%, P 59-91%, PTH 61-89%, and 28-77% considering all three targets together. The KDIGO guidelines recommend similar percentages except for P (33-77%). No differences were found related to eKt/V, online haemodiafiltration/HD, weight, body mass index, or dialysis vintage. They were only related to age, blood flow, effective treatment time, and dialysate calcium but without relevant clinical differences. Patients outside the target ranges generated significantly higher treatment costs. CONCLUSIONS: Compliance with mineral metabolism targets in HD patients was poor and showed a wide variation between treatment centres. PMID- 24217177 TI - The role of environmental reservoirs in human campylobacteriosis. AB - Campylobacteriosis is infection caused by the bacteria Campylobacter spp. and is considered a major public health concern. Campylobacter spp. have been identified as one of the most common causative agents of bacterial gastroenteritis. They are typically considered a foodborne pathogen and have been shown to colonise the intestinal mucosa of all food-producing animals. Much emphasis has been placed on controlling the foodborne pathway of exposure, particularly within the poultry industry, however, other environmental sources have been identified as important contributors to human infection. This paper aims to review the current literature on the sources of human exposure to Campylobacter spp. and will cover contaminated poultry, red meat, unpasteurised milk, unwashed fruit and vegetables, compost, wild bird faeces, sewage, surface water, ground water and drinking water. A comparison of current Campylobacter spp. identification methods from environmental samples is also presented. The review of literature suggests that there are multiple and diverse sources for Campylobacter infection. Many environmental sources result in direct human exposure but also in contamination of the food processing industry. This review provides useful information for risk assessment. PMID- 24217178 TI - Did we get our money's worth? Bridging economic and behavioral measures of program success in adolescent drug prevention. AB - The recent U.S. Congressional mandate for creating drug-free learning environments in elementary and secondary schools stipulates that education reform rely on accountability, parental and community involvement, local decision making, and use of evidence-based drug prevention programs. By necessity, this charge has been paralleled by increased interest in demonstrating that drug prevention programs net tangible benefits to society. One pressing concern is precisely how to integrate traditional scientific methods of program evaluation with economic measures of "cost efficiency". The languages and methods of each respective discipline don't necessarily converge on how to establish the true benefits of drug prevention. This article serves as a primer for conducting economic analyses of school-based drug prevention programs. The article provides the reader with a foundation in the relevant principles, methodologies, and benefits related to conducting economic analysis. Discussion revolves around how economists value the potential costs and benefits, both financial and personal, from implementing school-based drug prevention programs targeting youth. Application of heterogeneous costing methods coupled with widely divergent program evaluation findings influences the feasibility of these techniques and may hinder utilization of these practices. Determination of cost-efficiency should undoubtedly become one of several markers of program success and contribute to the ongoing debate over health policy. PMID- 24217179 TI - Biomedical progress rates as new parameters for models of economic growth in developed countries. AB - While the doubling of life expectancy in developed countries during the 20th century can be attributed mostly to decreases in child mortality, the trillions of dollars spent on biomedical research by governments, foundations and corporations over the past sixty years are also yielding longevity dividends in both working and retired population. Biomedical progress will likely increase the healthy productive lifespan and the number of years of government support in the old age. In this paper we introduce several new parameters that can be applied to established models of economic growth: the biomedical progress rate, the rate of clinical adoption and the rate of change in retirement age. The biomedical progress rate is comprised of the rejuvenation rate (extending the productive lifespan) and the non-rejuvenating rate (extending the lifespan beyond the age at which the net contribution to the economy becomes negative). While staying within the neoclassical economics framework and extending the overlapping generations (OLG) growth model and assumptions from the life cycle theory of saving behavior, we provide an example of the relations between these new parameters in the context of demographics, labor, households and the firm. PMID- 24217180 TI - A general model of dioxin contamination in breast milk: results from a study on 94 women from the Caserta and Naples areas in Italy. AB - BACKGROUND: The Caserta and Naples areas in Campania Region experience heavy environmental contamination due to illegal waste disposal and burns, thus representing a valuable setting to develop a general model of human contamination with dioxins (PCDDs-PCDFs) and dioxin-like-PCBs (dl-PCBs). METHODS: 94 breastfeeding women (aged 19-32 years; mean age 27.9 +/- 3.0) were recruited to determine concentrations of PCDDs-PCDFs and dl-PCBs in their milk. Individual milk samples were collected and analyzed according to standard international procedures. A generalized linear model was used to test potential predictors of pollutant concentration in breast milk: age, exposure to waste fires, cigarette smoking, diet, and residence in high/low risk area (defined at high/low environmental pressure by a specific 2007 WHO report). A Structural Equation Model (SEM) analysis was carried out by taking into account PCDDs-PCDFs and dl PCBs as endogenous variables and age, waste fires, risk area and smoking as exogenous variables. RESULTS: All milk samples were contaminated by PCDDs-PCDFs (8.6 pg WHO-TEQ/98g fat +/- 2.7; range 3.8-19) and dl-PCBs (8.0 pg WHO-TEQ/98g fat +/- 3.7; range 2.5-24), with their concentrations being associated with age and exposure to waste fires (p < 0.01). Exposure to fires resulted in larger increases of dioxins concentrations in people living in low risk areas than those from high risk areas (p < 0.01). CONCLUSIONS: A diffuse human exposure to persistent organic pollutants was observed in the Caserta and Naples areas. Dioxins concentration in women living in areas classified at low environmental pressure in 2007 WHO report was significantly influenced by exposure to burns. PMID- 24217181 TI - Economic rationality in choosing between short-term bad-health choices and longer term good-health choices. AB - Non-contagious, chronic disease has been identified as a global health risk. Poor lifestyle choices, such as smoking, alcohol, drug and solvent abuse, physical inactivity, and unhealthy diet have been identified as important factors affecting the increasing incidence of chronic disease. The following focuses on the circumstance affecting the lifestyle or behavioral choices of Aboriginal and Torres Strait Islander peoples in remote-/very remote Australia. Poor behavioral choices are the result of endogenous characteristics that are influenced by a range of stressful exogenous variables making up the psychosocial determinants including social disenfranchisement, cultural loss, insurmountable tasks, the loss of volitional control and resource constraints. It is shown that poor behavioral choices can be economically rational; especially under highly stressful conditions. Stressful circumstances erode individual capacity to commit to long-term positive health alternatives such as self-investment in education. Policies directed at removing the impediments and providing incentives to behaviors involving better health choices can lead to reductions in smoking and alcohol consumption and improved health outcomes. Multijurisdictional culturally acceptable policies directed at distal variables relating to the psychosocial determinants of health and personal mastery and control can be cost effective. While the content of this paper is focused on the conditions of colonized peoples, it has broader relevance. PMID- 24217182 TI - Solvent-type-dependent polymorphism and charge transport in a long fused-ring organic semiconductor. AB - Crystalline polymorphism of organic semiconductors is among the critical factors in determining the structure and properties of the resultant organic electronic devices. Herein we report for the first time a solvent-type-dependent polymorphism of a long fused-ring organic semiconductor and its crucial effects on charge transport. A new polymorph of 5,11 bis(triethylsilylethynyl)anthradithiophene (TES ADT) is obtained using solvent assisted crystallization, and the crystalline polymorphism of TES ADT thin films is correlated with their measured hole mobilities. The best-performing organic thin film transistors of the two TES ADT polymorphs show subthreshold slopes close to 1 V dec(-1), and threshold voltages close to zero, indicating that the density of traps at the semiconductor-dielectric interface is negligible in these devices and the observed up to 10-fold differences in hole mobilities of devices fabricated with different solvents are largely resultant from the presence of two TES ADT polymorphs. Moreover, our results suggest that the best-performing TES ADT devices reported in the literature correspond to the new polymorph identified in this study, which involves crystallization from a weakly polar solvent (such as toluene and chloroform). PMID- 24217183 TI - Investigation of a method for generating synthetic CT models from MRI scans of the head and neck for radiation therapy. AB - Magnetic resonance (MR) images often provide superior anatomic and functional information over computed tomography (CT) images, but generally are not used alone without CT images for radiotherapy treatment planning and image guidance. This study aims to investigate the potential of probabilistic classification of voxels from multiple MRI contrasts to generate synthetic CT ('MRCT') images. The method consists of (1) acquiring multiple MRI volumes: T1-weighted, T2-weighted, two echoes from a ultra-short echo time (UTE) sequence, and calculated fat and water image volumes using a Dixon method, (2) classifying tissues using fuzzy c means clustering with a spatial constraint, (3) assigning attenuation properties with weights based on the probability of individual tissue classes being present in each voxel, and (4) generating a MRCT image volume from the sum of attenuation properties in each voxel. The capability of each MRI contrast to differentiate tissues of interest was investigated based on a retrospective analysis of ten patients. For one prospective patient, the correlation of skull intensities between CT and MR was investigated, the discriminatory power of MRI in separating air from bone was evaluated, and the generated MRCT image volume was qualitatively evaluated. Our analyses showed that one MRI volume was not sufficient to separate all tissue types, and T2-weighted images was more sensitive to bone density variation compared to other MRI image types. The short echo UTE image showed significant improvement in contrasting air versus bone, but could not completely separate air from bone without false labeling. Generated MRCT and CT images showed similar contrast between bone and soft/solid tissues. These results demonstrate the potential of the presented method to generate synthetic CT images to support the workflow of radiation oncology treatment planning and image guidance. PMID- 24217185 TI - Generic medicine substitution: a cross-sectional survey of the perception of pharmacists in North-Central, Nigeria. AB - OBJECTIVE: To investigate the views of pharmacists in North-Central Nigeria on generic medicines and generic substitution practices. SUBJECTS AND METHOD: A cross-sectional survey was conducted in 4 cities in North-Central Nigeria from April to June 2012 among 330 pharmacists in hospital and community pharmacy settings, recruited through a convenience sampling strategy. Data were collected using a prevalidated self-administered questionnaire and entered into SPSS version 16.0 software to generate descriptive statistics. Binary logistic regression was conducted to determine the demographic predictors of preference for generic substitution among respondents. RESULTS: The response rate was 46.7% (n = 154). Eighty-four (54.5%) respondents reported that generic medicines were not of equivalent quality to branded ones. There was no significant difference (p > 0.05) in the perception of respondents regarding the quality of imported generic medicines over locally manufactured ones. While 143 (92.9%) respondents supported generic substitution practices, 105 (68.2%) would prefer to recommend generic medicines over branded ones. Hospital pharmacists were more likely (OR = 2.6; 95% CI 1.2-5.8) than community pharmacists to recommend generic medicines. One hundred and fifty-three (99.4%) respondents would support the implementation of a future generic substitution right for pharmacists in Nigeria. CONCLUSION: The present study showed a high support for generic substitution and future generic substitution rights for pharmacists in Nigeria. PMID- 24217186 TI - One-pot synthesis of size- and morphology-controlled 1-D iron oxide nanochains with manipulated magnetic properties. AB - Polypropylene grafted maleic anhydride (PP-MA, 2500 g mole(-1)) has demonstrated its unique capability to synthesize 1-D ferromagnetic hard (292.7 Oe) gamma-Fe2O3 nanochains made of ~24 nm nanoparticles vs. PP-MA with 8000 g mole(-1) for the synthesis of 1-D ferromagnetic soft (70.5 Oe) gamma-Fe2O3 nanochains (30 nm) made of flowerlike nanoparticles. PMID- 24217184 TI - Prognostic factors for disease-free survival after preoperative chemotherapy followed by curative resection in patients with colorectal cancer harboring hepatic metastasis: a single-institute, retrospective analysis in Asia. AB - BACKGROUND: Converting chemotherapy followed by surgery is known to be associated with improved clinical outcomes in colorectal cancer (CRC) patients with hepatic metastasis. This study is to investigate the clinicopathological prognostic factors for disease-free survival (DFS) after curative resection of primary and metastatic lesions. METHODS: We retrospectively analyzed the medical records of 76 CRC patients who had initially had unresectable hepatic metastasis, which was considered resectable after systemic chemotherapy, and had undergone curative surgery in the period from January 2006 to December 2011. DFS was compared by assessing clinical data including age, sex, staging, number of hepatic lesion(s), size of the largest hepatic lesion and serum carcinoembryonic antigen (CEA) levels. RESULTS: The median age was 57 years and 47 patients were male. The median DFS was 10.4 months. Multivariate Cox regression analysis revealed that age <50 years (HR 2.70, 95% CI 1.43-5.10, p = 0.002) and CEA elevation after curative surgery (HR 2.20, 95% CI 1.11-4.36, p = 0.023) were associated with a shorter DFS. CONCLUSIONS: Given that patients <50 years old or with elevated CEA levels after curative surgery demonstrated a short DFS, additional postoperative systemic treatment or active surveillance, at least, should strongly be considered for this group. PMID- 24217187 TI - Multiple sclerosis research: diagnostics, disease-modifying treatments, and emerging therapies. AB - Multiple sclerosis (MS) is a complex disease that affects the central nervous system. It is believed to be an immune mediated disease, and although the etiology remains unknown, it is believed to occur from a combination of genetic risk factors and environmental risk factors. There is no single diagnostic test for MS, and diagnostic criteria have been developed to aid the provider in making an accurate and timely diagnosis. Once a diagnosis of MS is made, treatments directed toward the inflammatory immune response should be initiated. Currently, there are 10 treatments for MS: four interferon beta products; one glatiramer acetate; one monoclonal antibody--natalizumab; three oral treatments--fingolimod, teriflunomide, and dimethyl fumarate; and one immunosuppressant agent- mitoxantrone. Each of these agents has a different administration and different risks and side effects. Numerous agents are in late stage development, and it is possible that several more agents, all with different mechanisms of action, will become available over the next several years. PMID- 24217188 TI - From the editor .... PMID- 24217189 TI - Impact of delayed diagnosis and treatment in clinically isolated syndrome and multiple sclerosis. AB - Multiple sclerosis (MS) is a progressive inflammatory disease with several possible clinical courses; before the development of definite MS, some patients may have clinically isolated syndrome (CIS), which is a single attack of neurological symptoms caused by inflammation or demyelination. Disease-modifying treatments (DMTs) have been extensively used for the management of MS, resulting in improvements in the clinical presentation and decreases in MS-associated neurological damage. Earlier initiation of DMT in the course of MS is associated with better outcomes. For patients with CIS, initiation of interferon-beta or glatiramer acetate treatment after an initial clinical event indicative of MS has been associated with delays in the progression to clinically definite MS as well as improvements in measures of neurological damage via magnetic resonance imaging. The initiation of treatment for patients with CIS should be considered, and nurses play a vital role in educating patients about the risks of conversion to MS and the benefits of early DMT. PMID- 24217190 TI - Pharmacogenetics: has the time come for pharmacists to embrace and implement the science? AB - Pharmacogenetics--the study of interindividual differences in medication response as a result of genetic variations--has emerged as a potentially useful tool for individualizing medication regimens for patients. Genetic variations can affect drug disposition inseveral ways, from modifying receptor sensitivities to impacting drug metabolism. Over the last several years, the Food and Drug Administration has been steadily including pharmacogenetic information in drug labeling for several commonly prescribed drugs. Several organizations are attempting to provide evidence-based guidelines for widespread implementation and interpretation. Pharmacists, armed with knowledge of drug metabolism pathways and drug-gene interactions, are uniquely positioned to play an active role in the education, provision, and clinical implementation of pharmacogenetics. PMID- 24217191 TI - Clinical, behavioral, and treatment differences in nursing facility residents with dementia, with and without pseudobulbar affect symptomatology. AB - OBJECTIVES: Characterize the prevalence and impact of crying and tearfulness as symptoms that may be suggestive of pseudobulbar affect (PBA) in residents of nursing facilities, including those with Alzheimer's disease (AD) and non-AD [non AD-associated] associated dementia. DESIGN: Data were extracted retrospectively from a large repository of de-identified and linked Minimum Data Set 2.0 (MDS) and prescription claims records for the period between October 1, 2009, and September 30, 2010. A score of 1 or 2 on MDS item E1m ("crying, tearfulness") was used to identify potential PBA. SETTING: 19,000 nursing facilities in 48 states. PATIENTS/PARTICIPANTS: Prescription and MDS records of nursing facility residents. MAIN OUTCOME MEASURES: Comparison of concomitant diagnoses, MDS mood, and behavioral indicators, and psychopharmacologic medication use, in residents with crying/tearfulness to a control group matched for age, gender, diagnosis of AD or non-AD dementia, and diagnosis of depression. RESULTS: A total of 137,829 residents underwent at least one MDS assessment during the study period. Of these, 12,595 (9.1%) had item E1m ("crying, tearfulness") scored as a 1 or 2 on their MDS assessments. Ten thousand residents were then randomly selected from this group and matched to 10,000 controls without "crying, tearfulness" (MDS E1m = 0) for analysis. A total of 4,786 (47.9%) unique residents with "crying, tearfulness" had a diagnosis of AD (8.8%), non-AD dementia (31.5%), or both (7.6%). All of the MDS mood indicators were at least twice as prevalent in this group compared with those without "crying, tearfulness" Additionally, mood symptoms such as anger, worried/pained facial expressions, and repetitive verbalizations; and behavioral symptoms such as verbal/physical abuse and socially inappropriate/disruptive behavior, were more than twice as frequent in the "crying, tearfulness" group. Antipsychotic medications were also used more often in this group (50% vs. 36.1%), as were antidepressants (59.1% vs. 49.8%). CONCLUSIONS: In the absence of an International Classification of Diseases 9th edition, Clinical Modification code, the presence of "crying, tearfulness" on MDS 2.0 item E1m was used as a proxy to identify potential PBA. Nursing facility residents with "crying, tearfulness" had a higher prevalence of all mood and behavior indicators as well as psychopharmacological medication use, compared with matched controls without "crying, tearfulness." Similar results were seen in the subgroup of residents with an underlying diagnosis of AD and/or non-AD dementia. Further research should validate the actual prevalence of PBA in this population, and the corresponding impact on resident outcomes. PMID- 24217193 TI - Bisphosphonate use in patients undergoing dialysis. AB - Bisphosphonates are efficacious for a variety of antiosteoporotic endpoints, most notably for vertebral, nonvertebral, and hip outcomes, including fractures. Currently the prevalence of osteoporosis in patients undergoing dialysis ranges from 13% to 80%. There are very limited data on the use of bisphosphonates within this population. This review discusses the available literature regarding bisphosphonates and dialysis. Contraindication to bisphosphonates, which are cleared renally, can be justifiable based on the pharmacokinetics. However, the medication and dialysis factors that should be considered if bisphosphonates are used in these patients include the amount of drug removed per dialysis session, the molecular weight, the percent protein-bound, sieving coefficient, dialysis membrane, blood-flow rates, and dialysis-flow rates.In addition, much data on bisphosphonates and dialysis are derived from nonosteoporosis studies. Furthermore, a large portion of patients requiring dialysis are at risk for osteoporosis and subsequent fractures, and may benefit from use of bisphosphonates. However, with a dearth of knowledge, more data are needed prior to making this a routine recommendation. PMID- 24217192 TI - Prevention and treatment of age-related macular degeneration: an update for pharmacists. AB - OBJECTIVE: Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). DATA SOURCES: Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. STUDY SELECTION AND DATA EXTRACTION: Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. CONCLUSION: AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements. PMID- 24217194 TI - New statin labeling requirements: an overview. AB - As pharmacists advocate for appropriate use of medications to ensure safety and efficacy for patients, labeling requirements for medications should be considered before patients start new therapies or make changes to their current therapies. In early 2012, the Food and Drug Administration released new mandatory labeling requirements for HMG-CoA reductase inhibitors (more commonly known as "statins") regarding hepatic dysfunction, cognitive impairment, and glycemic control. These requirements are based on a combination of studies, adverse-event reporting databases, and literature reviews. Pharmacists should be prepared to advocate for patient safety and be ready to inform patients and other health care providers of the new labeling requirements and the role pharmacists can play in altering current statin therapy. PMID- 24217195 TI - Plasma advanced glycation end products (AGEs), receptors for AGEs and their correlation with inflammatory markers in middle school-age children. AB - AIM: Advanced glycation end products (AGEs) and/or their receptors (RAGE) are significantly positively correlated with adiposity, inflammation, dyslipidemia, and insulin resistance in adults. However, the relationships between AGEs, RAGE, and adiposity-related comorbidites in children have not been well studied. METHODS: In a cross-sectional study of 88 children (age 11-15 years) from the New York area enrolled in the Reduce Obesity and Diabetes (ROAD) study, we examined the correlation of the AGE N(epsilon)-(carboxymethyl)lysine (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) with adiposity, inflammatory markers [interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha], adiponectin, lipids, insulin sensitivity, and insulin secretory capacity. RESULTS: Pediatric CML levels were ~20% below average adult levels. CML was significantly (p < 0.05) positively correlated with age and insulin sensitivity and negatively with adiposity, dyslipidemia and IL-6. sRAGE correlated positively with esRAGE and negatively with adiposity and IL-6. Both sRAGE and esRAGE correlated negatively with insulin secretory capacity. CONCLUSION: Our findings suggest that unlike adults, CML is negatively associated with adiposity and adiposity-related comorbidity risk in children. As in adults, sRAGE and esRAGE were, to varying degrees, negatively correlated with body fatness and risk factors for adiposity-related comorbidities. PMID- 24217196 TI - Effect of yogurt containing Bifidobacterium animalis subsp . lactis DN-173010 probiotic on dental plaque and saliva in orthodontic patients. AB - AIM: To assess how consumption of yogurt containing Bifidobacterium animalis subsp. lactis DN-173010 probiotic for a period of 2 weeks affects salivary and dental plaque levels of mutans streptococci and lactobacilli in patients undergoing orthodontic treatment. METHODS: A crossover, double-blind, randomized and placebo-controlled clinical trial was performed with 26 volunteers. The study was divided into four periods. During periods 2 and 4, the volunteers ingested yogurt containing probiotic or control yogurt daily for 2 weeks. Periods 1 and 3 were a 1-week run-in period and 4-week washout period, respectively. Saliva and dental plaque samples were collected from each participant at the end of each period. Mutans streptococci, lactobacilli, and total cultivable microorganisms were counted. Values were compared between groups and across periods with the Wilcoxon's test. RESULTS: There was no difference between the yogurt containing probiotic and the control yogurt for any of the studied variables (all p > 0.05). A reduction in counts of total cultivable microorganisms was observed in dental plaque samples after ingestion of either yogurts (both p < 0.05 vs. baseline), but not in saliva (p < 0.05). CONCLUSION: Daily ingestion of yogurt with or without B. animalis subsp. lactis for a period of 2 weeks was beneficial in reducing total microbial counts in dental plaque. Therefore, no additional benefits were achieved by the use of the tested probiotic strain. PMID- 24217198 TI - Rituximab maintenance therapy after autologous stem cell transplantation prolongs progression-free survival in patients with mantle cell lymphoma. PMID- 24217197 TI - On the way towards a 'CLL prognostic index': focus on TP53, BIRC3, SF3B1, NOTCH1 and MYD88 in a population-based cohort. PMID- 24217199 TI - Supernumerary isochromosome 1, idic(1)(p12), leading to tetrasomy 1q in Burkitt lymphoma. AB - Burkitt lymphoma (BL) is an aggressive mature B-cell neoplasm. The cytogenetic hallmark are MYC-involving translocations, most frequently as t(8;14)(q24;q32). Additional cytogenetic abnormalities are seen in the majority of cases. The most frequent additional aberration involves the long arm of chromosome 1, either as partial or complete trisomy 1q. A very rare additional aberration is a supernumerary isochromosome 1q, i(1)(q10), resulting in tetrasomy 1q. The biological significance of this aberration is unclear. We present a highly aggressive case of BL in a child with immature B-cell immunophenotype (IP) and supernumerary i(1)(q10). Diagnostic karyotyping showed 47,XY,+i(1)(q10),t(8;14)(q24;q32)[2]/47,idem,del(15)(q24)[21]/46,XY[2]. aCGH analysis detected a gain of 1p12qter and a loss of 15q22q25. FISH analysis confirmed the isodicentric chromosome 1, which has not previously been reported in BL. In the literature, supernumerary i(1)(q10) was found in 11 cases of which >80% presented with immature B-cell IP and >60% relapsed or died. Tetrasomy 1q resulting from supernumerary idic(1)(p12) or i(1)(q10) is a rare genetic event in BL and probably associated with immature B-cell IP. We propose that high amplification of genes on chromosome 1p12qter may contribute to the BL IP and disease progression. PMID- 24217200 TI - Colorectal cancer: screening-one small step for mankind, one giant leap for man. AB - Colorectal cancer (CRC) screening strongly reduces CRC-related mortality, with the effects of screening persisting for 20-30 years. These observations support current CRC screening and surveillance guidelines. At the population level, screening contributes to longer, healthier living. Thus, it is one small step for mankind, yet one giant leap for man. PMID- 24217201 TI - Lung cancer: drug-sensitivity--time for a rearrangement? PMID- 24217202 TI - Hepatocellular carcinoma: a teaspoon of sugar? PMID- 24217203 TI - Haematological cancer: abnormal chromosomes forecast rapid disease progression in SMM. PMID- 24217205 TI - Elevated ground-level O3 negatively influences paddy methanogenic archaeal community. AB - The current knowledge regarding the effect of global climate change on rice-paddy methane (CH4) emissions is incomplete, partly because information is limited concerning the mechanism of the microbial response to elevated ground-level ozone (O3). A field experiment was conducted in the China Ozone Free-Air Concentration Enrichment facility in a rice-wheat rotation system to investigate the responses of methanogenic archaeal communities to elevated ground-level O3 by culture independent and -reliant approaches. We found that elevated ground-level O3 inhibited methanogenic activity and influenced the composition of paddy methanogenic communities, reducing the abundance and diversity of paddy methanogens by adversely affecting dominant groups, such as aceticlastic Methanosaeta, especially at the rice tillering stage. Our results indicated that continuously elevated ground-level O3 would negatively influence paddy methanogenic archaeal communities and its critical ecological function. These findings will contribute to a comprehensive understanding of the responses and feedbacks of paddy ecosystems to global climate change. PMID- 24217206 TI - Making inferences on treatment effects from real world data: propensity scores, confounding by indication, and other perils for the unwary in observational research. PMID- 24217204 TI - Diffuse large B-cell lymphoma-treatment approaches in the molecular era. AB - Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell non-Hodgkin lymphoma that affects patients of all ages with a wide range of clinical presentations. Although DLBCL is curable even in advanced stages, up to one-third of patients will not achieve cure with initial therapy. In the modern era of rituximab-based therapy as the first-line treatment, the prognoses of patients who require salvage therapy are poor and most will eventually succumb to their disease. Insight into the complex molecular circuitry of DLBCL reveals a diverse range of somatic mutations and aberrant intracellular signalling pathways that characterize distinct molecular subsets of the disease. The next major breakthrough in DLBCL therapy during this 'molecular era' of disease definition will be the identification of combinations of novel agents that target the oncogenic drivers of these subsets. Well-conducted clinical trials, with translational molecular investigations, will be essential to achieve the goal of precision medicine and expand the number of patients with DLBCL who achieve a cure. PMID- 24217207 TI - Teenagers say slim cigarettes are "cool" and "classy". PMID- 24217208 TI - Hunt "strained" the law to try to close Lewisham Hospital services, say judges. PMID- 24217209 TI - NHS "pays twice" for patients at walk-in centres who are registered elsewhere, study finds. PMID- 24217210 TI - [Acute myocardial infarction complicated by acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography]. AB - Acute myocardial infarction is a rare complication of dobutamine stress echocardiography. We describe the case of a diabetic patient who presented with an anterior myocardial infarction complicated by an acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography, requiring five days' hospitalisation. Coronarography could not be performed because of inadequate medical facilities. PMID- 24217211 TI - Ventricular tachycardia-based long QT without hypocalcaemia after use of ibandronic acid. AB - Many drugs are known to cause lengthening of the QT interval. Ibandronic acid is a frequently used agent in the treatment of osteoporosis and is known to cause prolongation of the QT interval due to hypocalcaemia. However, no cases of long QT syndrome associated with ventricular tachycardia (VT) with a serum calcium level within the normal limits have been reported in the literature. We report on a case of a VT-based long QT syndrome associated with the use of ibandronic acid. PMID- 24217212 TI - Spontaneous retrograde dissection of the ascending aorta in a patient with a bicuspid aortic valve. AB - Bicuspid aortic valve (BAV) is a congenital anomaly associated with structural weakness of the aortic wall. Sudden onset of symptoms in patients with BAV, such as sudden severe back pain, and pulse inequality between the extremities or tension disparity should alert clinicians to acute aortic syndromes, as they require prompt diagnosis and management. Retrograde aortic dissection, which is a rare form of acute aortic syndrome, is an uncommon life-threatening entity and may produce atypical computed tomography (CT) or magnetic resonance imaging findings, leading to difficulty in diagnosis. We report on a 51-year-old male patient with BAV and spontaneous retrograde ascending aortic dissection. CT findings were confusing and the diagnosis was made via transoesophageal echocardiography. After the diagnosis, the patient was treated with a modified Bentall procedure. He did not have any complications and was stable four months after the operation. PMID- 24217214 TI - Theoretical prediction of a new two-dimensional carbon allotrope and NDR behaviour of its one-dimensional derivatives. AB - By using state of the art theoretical methods we have predicted a new two dimensional (2-D) carbon allotrope. This new planar carbon framework is made of hexagons, octagons and pentagons and hence named as HOP graphene (HOPG). The possibility of existence of HOPG is evident from its dynamical stability as confirmed by phonon-mode analysis and also from an energetic point of view since it is energetically more favorable than recently synthesized graphdiyne. The band structure shows the metallic behaviour of this new form of carbon allotrope. We also explored the electronic structure and transport properties of a 1-D derivative (nanoribbon) of HOPG. Most of the nanoribbons exhibit multiple negative differential resistance (NDR) behaviour with high peak to valley ratio. PMID- 24217213 TI - Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. AB - IMPORTANCE: In Duchenne muscular dystrophy (DMD), the reading frame of an out-of frame DMD deletion can be repaired by antisense oligonucleotide (AO)-mediated exon skipping. This creates a shorter dystrophin protein, similar to those expressed in the milder Becker muscular dystrophy (BMD). The skipping of some exons may be more efficacious than others. Patients with exon 44 or 45 skippable deletions (AOs in clinical development) have a less predictable phenotype than those skippable for exon 51, a group in advanced clinical trials. A way to predict the potential of AOs is the study of patients with BMD who have deletions that naturally mimic those that would be achieved by exon skipping. OBJECTIVE: To quantify dystrophin messenger RNA (mRNA) and protein expression in patients with DMD deletions treatable by, or mimicking, exon 44 or 45 skipping. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of nondystrophic controls (n = 2), patients with DMD (n = 5), patients with intermediate muscular dystrophy (n = 3), and patients with BMD (n = 13) at 4 university-based academic centers and pediatric hospitals. Biochemical analysis of existing muscle biopsies was correlated with the severity of the skeletal muscle phenotype. MAIN OUTCOMES AND MEASURES: Dystrophin mRNA and protein expression. RESULTS: Patients with DMD who have out-of-frame deletions skippable for exon 44 or 45 had an elevated number of revertant and trace dystrophin expression (approximately 19% of control, using quantitative immunohistochemistry) with 4 of 9 patients presenting with an intermediate muscular dystrophy phenotype (3 patients) or a BMD-like phenotype (1 patient). Corresponding in-frame deletions presented with predominantly mild BMD phenotypes and lower dystrophin levels (approximately 42% of control) than patients with BMD modeling exon 51 skipping (approximately 80% of control). All 12 patients with in-frame deletions had a stable transcript compared with 2 of 9 patients with out-of-frame deletions (who had intermediate muscular dystrophy and BMD phenotypes). CONCLUSIONS AND RELEVANCE: Exon 44 or 45 skipping will likely yield lower levels of dystrophin than exon 51 skipping, although the resulting protein is functional enough to often maintain a mild BMD phenotype. Dystrophin transcript stability is an important indicator of dystrophin expression, and transcript instability in DMD compared with BMD should be explored as a potential biomarker of response to AOs. This study is beneficial for the planning, execution, and analysis of clinical trials for exon 44 and 45 skipping. PMID- 24217215 TI - Computational and experimental investigations of CO2 and N2O fixation by sterically demanding N-heterocyclic carbenes (NHC) and NHC/borane FLP systems. AB - The sterically demanding NHCs 1,3-di-tert-butylimidazolin-2-ylidene (1a), 1,3-di tert-butyl-4,5-dimethylimidazolin-2-yildene (1b), and also the corresponding frustrated Lewis pair combinations 1a,b/B(C6F5)3 react readily with CO2 to form the NHC.CO2 (5a,b) and the NHC.CO2.B(C6F5)3 (9a,b) adducts, respectively. However, N2O activation and isolation of the NHC.N2O adduct (6) was only possible for NHC 1a. On heating, the NHC.N2O adduct 6 degrades to 1a, N2O, N2 and the urea derivative 7. Nevertheless, an NHC.N2O adduct of 1b was obtained with the FLP system 1b/B(C6F5)3. In contrast, for the FLP combination 1a/B(C6F5)3, N2O coordination appears to be slower than the self-deactivation. Hence, only the self-deactivation product 3 was observed under an N2O atmosphere. DFT calculations give insights into the CO2 and N2O activation process with 1a,b and 1a,b/B(C6F5)3. PMID- 24217217 TI - Guideline bone disease. AB - In the current issue of Blood Purification, Palomares et al. [Blood Purif 2013;36:122-131] bemoan the poor level of compliance in dialysis units in achieving compliance with KDOQI and KDIGO bone and mineral guideline targets. These targets are based almost completely on observational data and rely on an obsolete assay for PTH. The so-called intact PTH assay measures both 1-84 PTH and 7-84 PTH; the latter has been demonstrated to possess biological activity that is antagonistic to that of 1-84 PTH. The assay cannot reliably distinguish high from low bone turnover in the target ranges suggested by the guideline panels. Targeting these ranges leads to an increased incidence of adynamic bone disease, higher calcium and phosphorus, and likely poor patient outcomes. PMID- 24217216 TI - The importance of Arabidopsis glutathione peroxidase 8 for protecting Arabidopsis plant and E. coli cells against oxidative stress. AB - Glutathione peroxidases (GPXs) are major family of the reactive oxygen species (ROS) scavenging enzymes. Recently, database analysis of the Arabidopsis genome revealed a new open-reading frame, thus increasing the total number of AtGPX gene family to eight (AtGPX1-8). The effect of plant hormones like; i. e. salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA), indoleacetic acid (IAA), and mannitol on the expression of the genes confirm that the AtGPX genes family is regulated by multiple signaling pathways. The survival rate of AtGPX8 knockout plants (KO8) was significantly decreased under heat stress compared with the wild type. Moreover, the content of malondialdehyde (MDA) and protein oxidation was significantly increased in the KO8 plant cells under heat stress. Results indicating that the deficiency of AtGPX8 accelerates the progression of oxidative stress in KO8 plants. On the other hand, the overexpression of AtGPX8 in E. coli cells enhance the growth of the recombinant enzyme on media supplemented with 0.2 mM cumene hydroperoxide, 0.3 mM H 2O 2 or 600 mM NaCl. PMID- 24217218 TI - Natural variations in the stress and acute phase responses of cattle. AB - Activation of the innate immune system and acute phase response (APR) results in several responses that include fever, metabolic adaptations and changes in behavior. The APR can be modulated by many factors, with stress being the most common. An elevation of stress hormones for a short duration of time can be beneficial. However, elevation of stress hormones repeatedly or for an extended duration of time can be detrimental to the overall health and well-being of animals. The stress and APR responses can also be modulated by naturally occurring variations, such as breed, gender, and temperament. These three natural variations modulate both of these responses, and can therefore modulate the ability of an animal to recover from a stressor or infection. Understanding that cattle have different immunological responses, based on naturally occurring variations such as these, may be the foundation of new studies on how to effectively manage cattle so that health is optimized and production is benefited. PMID- 24217219 TI - Effects of coupled dose and rhythm manipulation of plasma cortisol levels on leukocyte transcriptional response to endotoxin challenge in humans. AB - Severe traumas are associated with hypercortisolemia due to both disruption of cortisol secretion rhythm and increase in its total concentration. Understanding the effects of altered cortisol levels and rhythms on immune function is of great clinical interest, to prevent conditions such as sepsis from complicating the recovery. This in vivo study assesses the responses of circulating leukocytes to coupled dose and rhythm manipulation of cortisol, preceding an immune challenge induced by endotoxin administration. Through continuous infusion, plasma cortisol concentration was increased to and kept constant at a level associated with major physiologic stress. In response, transcriptional programming of leukocytes was altered to display a priming response before endotoxin exposure. Enhanced expression of a number of receptors and signaling proteins, as well as lowered protein translation and mitochondrial function indicated a sensitization against potential infectious threats. Despite these changes, response to endotoxin followed very similar patterns in both cortisol and saline pre-treated groups except one cluster including probe sets associated with major players regulating inflammatory response. In sum, altered dose and rhythm of plasma cortisol levels engendered priming of circulating leukocytes when preceded an immune challenge. This transcriptional program change associated with stimulated surveillance function and suppressed energy-intensive processes, emphasized permissive actions of cortisol on immune function. PMID- 24217220 TI - The amazing innate immune response to influenza A virus infection. AB - Influenza A viruses (IAVs) remain a major health threat and a prime example of the significance of innate immunity. Our understanding of innate immunity to IAV has grown dramatically, yielding new concepts that change the way we view innate immunity as a whole. Examples include the role of p53, autophagy, microRNA, innate lymphocytes, endothelial cells and gut commensal bacteria in pulmonary innate immunity. Although the innate response is largely beneficial, it also contributes to major complications of IAV, including lung injury, bacterial super infection and exacerbation of reactive airways disease. Research is beginning to dissect out which components of the innate response are helpful or harmful. IAV uses its limited genetic complement to maximum effect. Several viral proteins are dedicated to combating innate responses, while other viral structural or replication proteins multitask as host immune modulators. Many host innate immune proteins also multitask, having roles in cell cycle, signaling or normal lung biology. We summarize the plethora of new findings and attempt to integrate them into the larger picture of how humans have adapted to the threat posed by this remarkable virus. We explore how our expanded knowledge suggests ways to modulate helpful and harmful inflammatory responses, and develop novel treatments. PMID- 24217221 TI - Endoplasmic reticulum stress is sufficient for the induction of IL-1beta production via activation of the NF-kappaB and inflammasome pathways. AB - The mechanisms underlying pathophysiological states such as metabolic syndrome and obesity include endoplasmic reticulum (ER) stress and aberrant inflammatory responses. ER stress results from the accumulation of misfolded proteins during stress conditions. However, the precise mechanisms by which ER stress modulates inflammation remain incompletely understood. In this study, we hypothesized that ER stress alone could represent a sufficient signal for the modulation of inflammasome-dependent cytokine responses. We found that several ER stress inducing chemicals and the free fatty acid palmitate can trigger IL-1beta secretion in various cell types, including monocytic leukemia cells, primary macrophages and differentiated adipocytes. We show that ER stress primes cells for the expression of pro-IL-1beta via NF-kappaB activation and promotes IL-1beta secretion. Enhanced IL-1beta secretion depended on the activation of the NLRP3 inflammasome through a mechanism involving reactive oxygen species formation and activation of thioredoxin-interacting protein. Chemical chaperone treatment and the pharmacological application of carbon monoxide inhibited IL-1beta secretion in response to ER stress. Our results provide a mechanistic link between ER stress and the regulation of inflammation, and suggest that modulation of ER stress may provide a therapeutic opportunity to block progression of low grade chronic inflammation to metabolic syndrome. PMID- 24217222 TI - ZnO nanorod arrays for various low-bandgap polymers in inverted organic solar cells. AB - Due to the limited diffusion length of carriers in polymer solar cells (PSCs), the path of carriers is a crucial factor that determines the device performance. Zinc oxide nanorods (NRs) as the electron transport channel can reduce electron hole recombination and transport the electron to the electrode efficiently for poly(3-hexylthiophene) (P3HT), but have been seldom demonstrated for low-bandgap polymers. Here we successfully applied ZnO NRs, which were grown via the hydrothermal method, as a platform to enhance PSC efficiency for various low bandgap polymers. In order to assure that the nanorod morphology functioned properly for PSCs, the growth time, the concentration, and the resulting morphology were systematically investigated in depths. Such ZnO NRs were applied to different organic systems, resulting in the increase of the PCE for PBDTTT C/PC71BM from 4.76% to 6.07% and PBDTTT-C-T/PC71BM from 5.40% to 7.34%. Through those experiments, we established a potentially universal and efficient ZnO NRs platform for various low-bandgap polymers to achieve high efficiency of inverted PSCs. PMID- 24217223 TI - Effects of elastase and collagenase on the nonlinearity and anisotropy of porcine aorta. AB - We use enzymatic manipulation methods to investigate the individual and combined roles of elastin and collagen on arterial mechanics. Porcine aortic tissues were treated for differing amounts of time using enzymes elastase and collagenase to cause degradation in substrate proteins elastin and collagen and obtain variable tissue architecture. We use equibiaxial mechanical tests to quantify the material properties of control and enzyme treated tissues and histological methods to visualize the underlying tissue microstructure in arterial tissues. Our results show that collagenase treated tissues were more compliant in the longitudinal direction as compared to control tissues. Collagenase treatment also caused a decrease in the tissue nonlinearity as compared to the control samples in the study. A one hour collagenase treatment was sufficient to cause fragmentation and degradation of the adventitial collagen. In contrast, elastase treatment leads to significantly stiffer tissue response associated with fragmented and incomplete elastin networks in the tissue. Thus, elastin in arterial walls distributes tensile stresses whereas collagen serves to reinforce the vessel wall in the circumferential direction and also contributes to tissue anisotropy. A microstructurally motivated strain energy function based on circumferentially oriented medial fibers and helically oriented collagen fibers in the adventitia is useful in describing these experimental results. PMID- 24217224 TI - They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice. AB - The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. PMID- 24217226 TI - AlPOs synthetic factor analysis based on maximum weight and minimum redundancy feature selection. AB - The relationship between synthetic factors and the resulting structures is critical for rational synthesis of zeolites and related microporous materials. In this paper, we develop a new feature selection method for synthetic factor analysis of (6,12)-ring-containing microporous aluminophosphates (AlPOs). The proposed method is based on a maximum weight and minimum redundancy criterion. With the proposed method, we can select the feature subset in which the features are most relevant to the synthetic structure while the redundancy among these selected features is minimal. Based on the database of AlPO synthesis, we use (6,12)-ring-containing AlPOs as the target class and incorporate 21 synthetic factors including gel composition, solvent and organic template to predict the formation of (6,12)-ring-containing microporous aluminophosphates (AlPOs). From these 21 features, 12 selected features are deemed as the optimized features to distinguish (6,12)-ring-containing AlPOs from other AlPOs without such rings. The prediction model achieves a classification accuracy rate of 91.12% using the optimal feature subset. Comprehensive experiments demonstrate the effectiveness of the proposed algorithm, and deep analysis is given for the synthetic factors selected by the proposed method. PMID- 24217225 TI - The ribonucleoprotein Csr network. AB - Ribonucleoprotein complexes are essential regulatory components in bacteria. In this review, we focus on the carbon storage regulator (Csr) network, which is well conserved in the bacterial world. This regulatory network is composed of the CsrA master regulator, its targets and regulators. CsrA binds to mRNA targets and regulates translation either negatively or positively. Binding to small non coding RNAs controls activity of this protein. Expression of these regulators is tightly regulated at the level of transcription and stability by various global regulators (RNAses, two-component systems, alarmone). We discuss the implications of these complex regulations in bacterial adaptation. PMID- 24217227 TI - The protective effect of Bcl-xl overexpression against oxidative stress-induced vascular endothelial cell injury and the role of the Akt/eNOS pathway. AB - Restenosis after intraluminal or open vascular reconstruction remains an important clinical problem. Vascular endothelial cell (EC) injury induced by oxidative stress plays an important role in the development of intimal hyperplasia. In this study, we sought to evaluate the protective effects of Bcl xl overexpression in vitro on oxidative stress-induced EC injury and the role of the Akt/endothelial nitric oxide synthase (eNOS) pathway. Human umbilical vein endothelial cells (HUVECs) exposed to hydrogen peroxide (H2O2, 0.5 mM) were used as the experimental oxidative stress model. The Bcl-xl gene was transferred into HUVECs through recombinant adenovirus vector pAdxsi-GFP-Bcl-xl before oxidative treatment. Cell apoptosis was evaluated by Annexin V/propidium iodide and Hoechst staining, caspase-7 and PARP cleavage. Cell viability was assessed using the cell counting kit-8 assay, proliferating cell nuclear antigen (PCNA) immunocytochemical detection and the scratching assay. Expressions of Akt, phospho-Akt and eNOS were detected by Western blotting. Our results showed that H2O2 induced apoptosis and decreased the cell viability of HUVECs. Bcl-xl overexpression significantly protected cells from H2O2-induced cell damage and apoptosis and maintained the cell function. Furthermore, the level of phospho-Akt and eNOS protein expression was significantly elevated when pretreated with Bcl xl gene transferring. These findings suggest that Bcl-xl overexpression exerts an anti-apoptotic and protective effect on EC function. The Akt/eNOS signaling pathway is probably involved in these processes. PMID- 24217230 TI - Unprecedented participation of a four-coordinate hydrogen atom in the cubane core of lithium and sodium phenolates. AB - Metalation of an ammonium tris(phenol) ligand affords new lithium/sodium derivatives having central pseudocubane motifs in which one of the metallic positions is replaced by a four-coordinate hydrogen atom. PMID- 24217229 TI - The ERK1/2 signaling pathway is involved in sulfur dioxide preconditioning induced protection against cardiac dysfunction in isolated perfused rat heart subjected to myocardial ischemia/reperfusion. AB - Ischemia/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO2) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway mediated protection against cardiac dysfunction after SO2 preconditioning in isolated rat hearts subjected to ischemia/reperfusion (I/R). Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 MUmol/L SO2 group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1 benzopyran-4-one (PD98059) + 5 MUmol/L SO2 (PD98059 + S5) group, PD98059 group, I/R group, 5 MUmol/L SO2 + I/R (S5 + I/R) group and PD98059 + 5 MUmol/L SO2 + I/R (PD98059 + S5 + I/R) group. Cardiac function and myocardial phosphorylated ERK1/2 protein were measured. We found that I/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1/2 protein. SO2 preconditioning markedly suppressed phosphorylated ERK1/2 protein and improved cardiac function in isolated rat heart with I/R (p < 0.05). However, pre treatment with PD98059 could prevent the above effects of SO2 preconditioning. In conclusion, SO2 preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I/R via suppression of the over-activation of the ERK1/2 signaling pathway. PMID- 24217228 TI - How Parkinsonian toxins dysregulate the autophagy machinery. AB - Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone) have been widely employed as in vivo and in vitro chemical models of Parkinson's disease (PD). Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD. PMID- 24217231 TI - Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. AB - OBJECTIVE: Whether or not cisplatin and cetuximab are similarly effective in improving outcomes when added to radiation therapy (RT) in squamous cell carcinoma of the head and neck is unknown. METHODS: Retrospective analysis was performed of patients treated with definitive RT and cisplatin (n = 18) or cetuximab (n = 29). RESULTS: T and N classifications, stage, human papillomavirus status and smoking history were balanced in the two groups; however, patients in the cisplatin group were younger and had a better performance status. Delivery of RT was similar between the two groups. Median follow-up was 23 (4-64) months. Disease-specific survival (DSS) at 3 years was 83% in the cisplatin group and 31% in the cetuximab group. Recurrent disease was more common in the cetuximab group compared with the cisplatin group (17 vs. 4 patients). Propensity score analysis to adjust for differences in patient characteristics which influenced treatment selection showed that DSS was indeed longer with cisplatin than with cetuximab (DSS hazard ratio 0.15, confidence interval 0.033, 0.66; p = 0.012). CONCLUSIONS: DSS was superior in the patients given cisplatin with definitive RT compared to cetuximab with definitive RT due to a lower risk of recurrent disease in the cisplatin group. These observations could not be explained by differences between the two groups in the patient and tumor characteristics or in treatment delivery. PMID- 24217232 TI - Importance effects on age differences in performance in event-based prospective memory. AB - BACKGROUND: Most laboratory-based studies on prospective memory show a decline with increasing age. Theoretical explanations for age differences focus on the allocation of attentional resources to support prospective remembering. The recruitment of prospective memory target monitoring seems to be influenced by perceived task importance. OBJECTIVE: In the present study, we investigated the influence of task importance on the magnitude of age differences in event-based prospective memory. METHODS: Healthy younger (n = 25) and older (n = 25) adults were instructed a priori to prioritize either the ongoing or the prospective memory task before performing an event-based prospective memory task. RESULTS: We found an interaction between age and task importance: instructed higher importance of the ongoing task compared to the prospective memory task component produced significant age-related declines in prospective remembering. By contrast, if older adults treated the prospective memory task component as more important than the ongoing task, they achieved equivalent levels of prospective memory performance as their younger counterparts, but did so at a cost to ongoing task performance. CONCLUSIONS: The present data indicate that task importance is one of the factors determining the presence or absence of age deficits in prospective remembering. Findings are discussed in the context of limited processing resources in old age and theoretical frameworks of event-based prospective memory. (c) 2013 S. Karger AG, Basel. PMID- 24217233 TI - Neuro-ophthalmology in Switzerland. PMID- 24217234 TI - A novel method to quantify dentine tubule occlusion applied to in situ model samples. AB - OBJECTIVES: To develop an innovative computerised routine, in conjunction with a minimally destructive imaging technique, to quantify dentine tubule occlusion. METHODS: Polished human dentine samples (n = 480) were brushed during a 4-day in situ study with two occlusion-based dentifrices, a sodium fluoride control dentifrice (1,450 ppm) or water. Samples were imaged with tandem scanning microscopy (TSM) and conventional scanning electron microscopy (SEM). The level of dentine patency was then assessed using a visual ordinal scale ('standard') or quantitatively using a specially designed computational routine. RESULTS: The occlusion-based dentifrice resulted in significantly less patent dentine than controls for the 'standard' (p = 0.01) assessment, but not for computer analyses (p = 0.10). The correlation of the number of individual patent tubules counted visually and by the computational routine in calibrations and in the in situ study was >= 0.8. CONCLUSIONS: This study identified a new computer-based routine, capable of objectively quantifying the patency of dentine imaged by SEM and TSM. PMID- 24217235 TI - What happens to functional mitral regurgitation after aortic valve replacement for aortic stenosis? AB - BACKGROUND: Patients with aortic stenosis (AS) treated with aortic valve replacement (AVR) may also present with associated functional mitral valve regurgitation (FMR). Whether to also address the mitral valve at the time of AVR remains unclear. This study was designed to determine the influence of MR on survival and its evolution over time. METHODS: We retrospectively reviewed 74 patients with FMR who underwent isolated AVR between 1999 and 2006 at our institution. Inclusion criteria were surgery for AVR with severe AS (mean age, 69 years; N = 47; 64% women) and FMR (grade I, 80%; grade II, 19%; grade III, 1%). Echocardiography follow-up data were obtained by mail questionnaires sent to the referring cardiologists of all survivors. All parameters were analyzed with the Kaplan-Meier method and the sign test. RESULTS: The operative mortality rate was 2%, and 9 patients (12%) died during follow-up. The mean (SD) follow-up time was 48 +/- 33 months, and follow-up 96% complete. The follow-up demonstrated a decrease of FMR by 2 degrees in 3 patients (4%), and 1 degree in 14 patients (19%); regurgitation remained unchanged in the majority of patients (n = 47; 63%). FMR worsened in 10 patients overall (14%), and new-onset atrial fibrillation was found in 24 patients (33%); however, the statistical analysis failed to demonstrate an impact of worsening FMR on survival. CONCLUSION: MR in patients with severe AS and FMR at the time of AVR does not appear to worsen significantly over time. Not dealing with the mitral valve at the time of AVR might be warranted for selected patients. PMID- 24217236 TI - The relationship between low intraoperative hematocrit levels during cardiopulmonary bypass and postoperative neurological events. AB - OBJECTIVE: The objective of our study is to analyze whether low intraoperative hematocrit levels have an effect upon postoperative neurological events. METHODS: Our study included 140 patients who underwent isolated coronary bypass under cardiopulmonary bypass between 2009 and 2012. The main group of the study was 70 patients with intraoperative hematocrit levels lower than 22%. These patients' 30 day postoperative neurological (particularly stroke) follow up was registered as the main data of the study. Another group of 70 patients possessing the same demographic features who underwent open heart surgery with hematocrit levels remaining above 22% were registered as the control group for perioperative neurological data. RESULTS: The average age of the patients with hematocrit levels below and above 22% was 56.8 +/- 5.8 years and 54.1 +/- 7.3 years, respectively. The mean follow-up period of the patients was 37.2 +/- 8.6 days. None of the patients had any neurological postoperative sequalae. No mortalities occurred. One patient who had mild paresthesia and motor weakness of the left hand had no pathological finding on computed tomography and was diagnosed with peripheral neuropathy due to intraoperative sternal retraction. CONCLUSION: Because our study revealed no cerebrovascular events, coronary bypass surgery under cardiopulmonary bypass may be safely conducted even in patients with hematocrit levels lower than 22%. PMID- 24217237 TI - Comparison of conventional technique and ultrasonographic mapping in saphenous vein harvesting. AB - BACKGROUND: Saphenous vein mapping provides accurate identification of the graft diameter, location of the harvest side, and quality of graft and also led to a selective leg skin incision. In this article, we aimed to compare patients who underwent coronary artery bypass graft (CABG) surgery with or without vein mapping. METHODS: Patients who underwent CABG surgery with saphenous vein grafts (SVG) between January 2005 and January 2010 in our service were analyzed retrospectively. One hundred seventy-eight 178 SVGs were harvested with classical methods (Group A), and 136 SVGs were harvested after Doppler ultrasonography (USG) mapping (Group B). RESULTS: In Group A, 6.7% of patients needed additional incisions for graft harvesting than planned before CABG surgery due to unsuitable vein grafts. In Group B, SVGs were harvested from left lower extremity in 16 patients, and the saphenous vein was not suitable for grafting in 1 patient due to Doppler examination. In the postoperative period, complications at the incision site were reduced in Group B. CONCLUSION: Preoperative vein mapping for harvesting SVGs is an effective method in reducing wound site complications, hospital stay, and hospital costs and in increasing patient comfort and satisfaction. PMID- 24217238 TI - Long-term outcomes following alemtuzumab induction in lung transplantation. AB - OBJECTIVES: Alemtuzumab is a commonly used induction agent for solid-organ transplantation. Its use in lung transplantation with reduced immunosuppressive regimens, however, has yet to be well characterized. METHODS: From November 2006 to March 2008, 20 consecutive lung transplantation patients received alemtuzumab induction with a reduced maintenance immunosuppression regimen. Twenty consecutive case-controls who underwent transplantation between 2005 and 2006 were treated with a standard immunosuppression regimen without induction. Outcome variables were patient survival, acute rejection, infection, and bronchiolitis obliterans syndrome. RESULTS: Mean follow-up time was 1400 days in the alemtuzumab group and 1210 days in the control group. Double lung transplantation was performed in 21 patients (12 in the alemtuzumab group and 9 in the control group). There was no difference in survival between the alemtuzumab (n = 10) and control (n = 10) groups. There was also not a significant difference in time adjusted death based on Kaplan-Meier analysis. The mean number of any grade of rejection event per patient was not significantly different (alemtuzumab 2.3 +/- 2.7 vs. control 3.2 +/- 2.35; P = .22). There was a trend toward the reduced incidence of infection requiring intravenous antibiotics per patient (alemtuzumab 2.4 vs. control 3.8; P = .08). The incidence of bronchiolitis obliterans syndrome was similar in both groups (alemtuzumab 55% vs. control 70%; P = .25). CONCLUSIONS: Alemtuzumab induction with reduced immunosuppression offers a comparable 5-year survival and rejection rate compared to standard-dose immunosuppression regimen. PMID- 24217239 TI - The application of on-pump beating-heart surgery for partial atrioventricular septal defect: a report of 87 cases. AB - BACKGROUND: Partial atrioventricular septal defect (P-AVSD) is a common congenital heart disease. Because of the presence of left and right atrioventricular valve deformities and the shift in the atrioventricular node and cardiac conduction bundle, the surgical repair of P-AVSD is difficult. This study was performed to compare the effects on the coronary sinus septum in the left versus the right atrium during surgical treatment for P-AVSD and report our experiences regarding the application of on-pump beating heart surgery under mild hypothermia for patients with P-AVSD. MATERIALS AND METHODS: The effects of on pump beating heart surgery were analyzed retrospectively in 87 P-AVSD patients. Of the 87 total patients, 84 with anterior mitral leaflet cleft underwent valvuloplasty and 3 underwent mitral valve replacement. Seventy-seven patients underwent tricuspid valve annuloplasty, 2 underwent tricuspid valve replacement, and 1 underwent left superior vena cava ligation, and 3 patients with atrial fibrillation were treated with radiofrequency ablation. Patients with an ostium primum atrial septal defect underwent autologous pericardial modified Kirklin repair. Of these, 46 patients had their coronary sinus septum separated into the left atrium and 41 had their coronary sinus retained in the right atrium. Fingertip oxygen saturation was compared between patients in whom the coronary sinus was separated to the left atrium and those in whom the coronary sinus was retained in the right atrium. RESULTS: There was 1 postoperative early death (1.15%) due to respiratory failure, and 1 patient had a III degree atrioventricular block (1.15%) and underwent implantation of a permanent pacemaker. The fingertip oxygen saturation levels of the left atrium group were 96.81 +/- 3.17 preoperatively, 95.37 +/- 4.62 at 7 days postoperatively, and 94.53 +/- 4.95 at 3 months postoperatively. Those of the right atrium group were 98.53 +/- 2.84 preoperatively, 97.19 +/- 3.57 at 7 days postoperatively, and 96.89 +/- 4.19 at 3 months postoperatively. During the follow-up period, which ranged from 3 months to 7 years, the cardiac function was adequately restored. CONCLUSIONS: On-pump beating heart surgery under mild hypothermia is a safe and feasible method. The retention of the coronary sinus in the right atrium might maintain oxygen saturation. PMID- 24217240 TI - Huge aortic pseudoaneurysm arising from the aorta-saphenous vein graft anastomosis after coronary artery bypass grafting. AB - Pseudoaneurysm of the aortic root is a rare condition and potentially fatal if not treated. It may occur in different etiologies. In this case, we aim to show an aortic pseudoaneurysm arising from the aorta-saphenous vein graft anastomosis. PMID- 24217241 TI - Pharmacokinetics of intraluminally administered serum papaverine for spasm prophylaxis of the internal mammary artery. AB - BACKGROUND: Papaverine (Paveron NTM Linden Arzneimittel Vertrieb GmbH, Germany) is a widely used agent for preventing spasm in mammary artery preparations. The question addressed in this study is whether the intraluminal administration of papaverine can result in detectable absorption of the drug into the systemic arterial circulation. METHODS: In 15 patients (age 65 +/- 6 years; body mass index 28.9 +/- 3.7), an internal mammary artery (IMA) was prepared during coronary artery bypass grafting (CABG). A maximum of 3 mL of a 1 mg/1 mL diluted papaverine solution was injected intravascularly (intraluminally) for spasm prophylaxis. The IMA was closed proximally and distally with bulldog clamps. Blood samples were taken immediately after administration (T1), after 20 minutes (T2), and at the end of the operation (T3). Samples were measured in a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system consisting of a binary pump from Agilent (Waldbronn, Germany) coupled to a high-throughput screening (HTS) PAL injection system (CTC, Zwingen, Switzerland) and a tandem mass spectrometer (API 4000, AB Sciex, Darmstadt, Germany). Papaverine was analyzed in positive mode using an electrospray ion source. Quantitation was performed using Analyst 1.5 software (AB Sciex, Darmstadt, Germany). RESULTS: The newly developed LC-MS/MS method was successfully established for the detection of papaverine in plasma samples. The highest plasma papaverine levels were determined at time point T1 (mean 54.7 +/- 39 ng/mL, range 16.6-179 ng/mL). The concentration was already halved 20 minutes after administration (T2) (mean 23.3 +/- 2 ng/mL, range 4.6-118 ng/mL). Because of the short half-life and the hemodilution in the extracorporeal circulation, at the end of the operation papaverine (T3) had already fallen to just above the limit of detection (mean 4.1 +/- 3.9 ng/mL, range 1.3-16.9 ng/mL). At time point T1, a significant negative correlation was determined between plasma levels and systemic diastolic, but not systolic, blood pressure. CONCLUSION: Papaverine was successfully determined systemically in plasma by LC-MS/MS after intraluminal administration in the IMA. Systemic circulatory effects are dependent on the detected quantity. Group size and the absence of a control group are considerable limitations. PMID- 24217243 TI - Hydrogen mimicking the properties of coinage metal atoms in Cu and Ag monohydride clusters. AB - A systematic study of the electronic structure and equilibrium geometries of Cun, Cun-1H, Agn, and Agn-1H; n = 2-5 clusters is carried out using photoelectron spectroscopy (PES) experiments and density functional theory based calculations. Our objective is to see if the substitution of a coinage metal atom by hydrogen would retain the electronic structure of the parent metal cluster since both systems are isoelectronic. For clusters with n >= 3, we find that the measured PES and vertical detachment energies (VDEs) (i.e. energies necessary to remove an electron from the anionic Mn(-) (M = Cu, Ag) clusters without changing their geometries) are close to those of Mn-1H(-) clusters, suggesting that substitution of a metal atom with hydrogen does not perturb the electronic structure of the parent cluster anion significantly. Calculated VDEs agree very well with experiment validating the theoretical methods used as well as the geometries of the neutral and anionic clusters. PMID- 24217242 TI - A DNA-based method for studying root responses to drought in field-grown wheat genotypes. AB - Root systems are critical for water and nutrient acquisition by crops. Current methods measuring root biomass and length are slow and labour-intensive for studying root responses to environmental stresses in the field. Here, we report the development of a method that measures changes in the root DNA concentration in soil and detects root responses to drought in controlled environment and field trials. To allow comparison of soil DNA concentrations from different wheat genotypes, we also developed a procedure for correcting genotypic differences in the copy number of the target DNA sequence. The new method eliminates the need for separation of roots from soil and permits large-scale phenotyping of root responses to drought or other environmental and disease stresses in the field. PMID- 24217244 TI - Continuous-flow cytomorphological staining and analysis. AB - Cells suspended in bodily fluids are routinely analyzed by cytopathologists as a means of diagnosing malignancies and other diseases. The physical and morphological properties of these suspended cells are evaluated in making diagnostic decisions, which often requires manual concentration, staining, and washing procedures to extract information about intracellular architecture. The need to manually prepare slides for analysis by a cytopathologist is a labor intensive process, which is ripe for additional automation to reduce costs but also to potentially provide more repeatable and improved accuracy in diagnoses. We have developed a microfluidic system to perform several steps in the preparation of samples for cytopathology that (i) automates colorimetric staining on-chip, and (ii) images cells in flow, as well as provides (iii) additional quantitative analyses of captured images to aid cytopathologists. A flow-through approach provides benefits by allowing staining and imaging to be performed in a continuous, integrated manner, which also overcomes previous challenges with in suspension colorimetric staining. We envision such a tool may reduce costs and aid cytopathologists in identifying rare or characteristic cells of interest by providing isolated images along with quantitative metrics on single cells from various rotational angles, allowing efficient determination of disease etiology. PMID- 24217245 TI - Tip110 protein binds to unphosphorylated RNA polymerase II and promotes its phosphorylation and HIV-1 long terminal repeat transcription. AB - Transcription plays an important role in both HIV-1 gene expression and replication and mandates complicated but coordinated interactions between the host and virus. Our previous studies have shown that an HIV-1 Tat-interacting protein of 110 kDa, Tip110, binds to and enhances Tat function in Tat-mediated HIV-1 gene transcription and replication (Liu, Y., Li, J., Kim, B. O., Pace, B. S., and He, J. J. (2002) HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110. J. Biol. Chem. 277, 23854-23863). However, the underlying molecular mechanisms by which this takes place were not understood. In this study, we demonstrated that Tip110 bound to unphosphorylated RNA polymerase II (RNAPII) in a direct and specific manner. In addition, we detected Tip110 at the HIV-1 long terminal repeat (LTR) promoter and found that Tip110 expression was associated with increased phosphorylation of serine 2 of the heptapeptide repeats within the RNAPII C-terminal domain and increased recruitment of positive transcription elongation factor b to the LTR promoter. Consistent with these findings, we showed that Tip110 interaction with Tat directly enhanced transcription elongation of the LTR promoter. Taken together, these findings have provided additional and mechanistic evidence to support Tip110 function in HIV-1 transcription. PMID- 24217246 TI - Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin bypassing ability acts similarly. AB - For iron-sulfur (Fe-S) cluster synthesis in mitochondria, the sulfur is derived from the amino acid cysteine by the cysteine desulfurase activity of Nfs1. The enzyme binds the substrate cysteine in the pyridoxal phosphate-containing site, and a persulfide is formed on the active site cysteine in a manner depending on the accessory protein Isd11. The persulfide is then transferred to the scaffold Isu, where it combines with iron to form the Fe-S cluster intermediate. Frataxin is implicated in the process, although it is unclear where and how, and deficiency causes Friedreich ataxia. Using purified proteins and isolated mitochondria, we show here that the yeast frataxin homolog (Yfh1) directly and specifically stimulates cysteine binding to Nfs1 by exposing substrate-binding sites. This novel function of frataxin does not require iron, Isu1, or Isd11. Once bound to Nfs1, the substrate cysteine is the source of the Nfs1 persulfide, but this step is independent of frataxin and strictly dependent on Isd11. Recently, a point mutation in Isu1 was found to bypass many frataxin functions. The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity. We propose a regulatory mechanism for the Nfs1 persulfide-forming activity. Specifically, at least two separate conformational changes must occur in the enzyme for optimum activity as follows: one is mediated by frataxin interaction that exposes the "buried" substrate binding sites, and the other is mediated by Isd11 interaction that brings the bound substrate cysteine and the active site cysteine in proximity for persulfide formation. PMID- 24217247 TI - Heat shock protein 90-alpha mediates aldo-keto reductase 1B10 (AKR1B10) protein secretion through secretory lysosomes. AB - Aldo-keto reductase 1B10 (AKR1B10) protein is a new tumor biomarker in humans. Our previous studies have shown that AKR1B10 is secreted through a lysosome mediated nonclassical pathway, leading to an increase in the serum of breast cancer patients. This study illuminates the regulatory mechanism of AKR1B10 secretion. The cytosolic AKR1B10 associates with and is translocated to lysosomes by heat shock protein 90alpha (HSP90alpha), a chaperone molecule. Ectopic expression of HSP90alpha significantly increased the secretion of endogenous AKR1B10 and exogenous GFP-AKR1B10 fusion protein when cotransfected. Geldanamycin, a HSP90alpha inhibitor, dissociated AKR1B10-HSP90alpha complexes and significantly reduced AKR1B10 secretion in a dose-dependent manner. We characterized the functional domain in AKR1B10 and found that helix 10 (amino acids 233-240), located at the C terminus, regulates AKR1B10 secretion. Targeted point mutations recognized that amino acids Lys-233, Glu-236, and Lys-240 in helix 10 mediate the interaction of AKR1B10 with HSP90alpha. Together, our data suggest that HSP90alpha mediates AKR1B10 secretion through binding to its helix 10 domain. This finding is significant in exploiting the use of AKR1B10 in cancer clinics. PMID- 24217248 TI - Intestinal cell proliferation and senescence are regulated by receptor guanylyl cyclase C and p21. AB - Guanylyl cyclase C (GC-C) is expressed in intestinal epithelial cells and serves as the receptor for bacterial heat-stable enterotoxin (ST) peptides and the guanylin family of gastrointestinal hormones. Activation of GC-C elevates intracellular cGMP, which modulates intestinal fluid-ion homeostasis and differentiation of enterocytes along the crypt-villus axis. GC-C activity can regulate colonic cell proliferation by inducing cell cycle arrest, and mice lacking GC-C display increased cell proliferation in colonic crypts. Activation of GC-C by administration of ST to wild type, but not Gucy2c(-/-), mice resulted in a reduction in carcinogen-induced aberrant crypt foci formation. In p53 deficient human colorectal carcinoma cells, ST led to a transcriptional up regulation of p21, the cell cycle inhibitor, via activation of the cGMP responsive kinase PKGII and p38 MAPK. Prolonged treatment of human colonic carcinoma cells with ST led to nuclear accumulation of p21, resulting in cellular senescence and reduced tumorigenic potential. Our results, therefore, identify downstream effectors for GC-C that contribute to regulating intestinal cell proliferation. Thus, genomic responses to a bacterial toxin can influence intestinal neoplasia and senescence. PMID- 24217249 TI - Substrate specificity and subcellular localization of the aldehyde-alcohol redox coupling reaction in carp cones. AB - Our previous study suggested the presence of a novel cone-specific redox reaction that generates 11-cis-retinal from 11-cis-retinol in the carp retina. This reaction is unique in that 1) both 11-cis-retinol and all-trans-retinal were required to produce 11-cis-retinal; 2) together with 11-cis-retinal, all-trans retinol was produced at a 1:1 ratio; and 3) the addition of enzyme cofactors such as NADP(H) was not necessary. This reaction is probably part of the reactions in a cone-specific retinoid cycle required for cone visual pigment regeneration with the use of 11-cis-retinol supplied from Muller cells. In this study, using purified carp cone membrane preparations, we first confirmed that the reaction is a redox-coupling reaction between retinals and retinols. We further examined the substrate specificity, reaction mechanism, and subcellular localization of this reaction. Oxidation was specific for 11-cis-retinol and 9-cis-retinol. In contrast, reduction showed low specificity: many aldehydes, including all-trans-, 9-cis-, 11-cis-, and 13-cis-retinals and even benzaldehyde, supported the reaction. On the basis of kinetic studies of this reaction (aldehyde-alcohol redox-coupling reaction), we found that formation of a ternary complex of a retinol, an aldehyde, and a postulated enzyme seemed to be necessary, which suggested the presence of both the retinol- and aldehyde-binding sites in this enzyme. A subcellular fractionation study showed that the activity is present almost exclusively in the cone inner segment. These results suggest the presence of an effective production mechanism of 11-cis-retinal in the cone inner segment to regenerate visual pigment. PMID- 24217250 TI - Common polymorphisms in human langerin change specificity for glycan ligands. AB - Langerin, a C-type lectin on Langerhans cells, mediates carbohydrate-dependent uptake of pathogens in the first step of antigen presentation to the adaptive immune system. Langerin binds a diverse range of carbohydrates including high mannose structures, fucosylated blood group antigens, and glycans with terminal 6 sulfated galactose. Mutagenesis and quantitative binding assays indicate that salt bridges between the sulfate group and two lysine residues compensate for the nonoptimal binding of galactose at the primary Ca(2+) site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys-313, to isoleucine. Glycan array screening reveals that this amino acid change abolishes binding to oligosaccharides with terminal 6SO4-Gal and enhances binding to oligosaccharides with terminal GlcNAc residues. Structural analysis shows that enhanced binding to GlcNAc may result from Ile-313 packing against the N-acetyl group. The K313I polymorphism is tightly linked to another SNP that results in the change N288D, which reduces affinity for glycan ligands by destabilizing the Ca(2+)-binding site. Langerin with Asp-288 and Ile 313 shows no binding to 6SO4-Gal-terminated glycans and increased binding to GlcNAc-terminated structures, but overall decreased binding to glycans. Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms. PMID- 24217251 TI - Isoform-selective oligomer formation of Saccharomyces cerevisiae p24 family proteins. AB - p24 family proteins are evolutionarily conserved transmembrane proteins involved in the early secretory pathway. Saccharomyces cerevisiae has 8 known p24 proteins that are classified into four subfamilies (p24alpha, -beta, -gamma, and -delta). Emp24 and Erv25 are the sole members of p24beta and -delta, respectively, and deletion of either destabilizes the remaining p24 proteins, resulting in p24 null phenotype (p24Delta). We studied genetic and physical interactions of p24alpha (Erp1, -5, and -6) and gamma (Erp2, -3, and -4). Deletion of the major p24alpha (Erp1) partially inhibited p24 activity as reported previously. A second mutation in either Erp5 or Erp6 aggravated the erp1Delta phenotype, and the triple mutation gave a full p24Delta phenotype. Similar genetic interactions were observed among the major p24gamma (Erp2) and the other two gamma members. All the p24alpha/gamma isoforms interacted with both p24beta and -delta. Interaction between p24beta and -delta was isoform-selective, and five major alpha/gamma pairs were detected. These results suggest that the yeast p24 proteins form functionally redundant alphabetagammadelta complexes. We also identified Rrt6 as a novel p24delta isoform. Rrt6 shows only limited sequence identity (~15%) to known p24 proteins but was found to have structural properties characteristic of p24. Rrt6 was induced when cells were grown on glycerol and form an additional alphabetagammadelta complex with Erp3, Erp5, and Emp24. This complex was mainly localized to the Golgi, whereas the p24 complex containing Erv25, instead of Rrt6 but otherwise with the same isoform composition, was found mostly in the ER. PMID- 24217252 TI - Receptor protein-tyrosine phosphatase alpha regulates focal adhesion kinase phosphorylation and ErbB2 oncoprotein-mediated mammary epithelial cell motility. AB - We investigated the role of protein-tyrosine phosphatase alpha (PTPalpha) in regulating signaling by the ErbB2 oncoprotein in mammary epithelial cells. Using this model, we demonstrated that activation of ErbB2 led to the transient inactivation of PTPalpha, suggesting that attenuation of PTPalpha activity may contribute to enhanced ErbB2 signaling. Furthermore, RNAi-induced suppression of PTPalpha led to increased cell migration in an ErbB2-dependent manner. The ability of ErbB2 to increase cell motility in the absence of PTPalpha was characterized by prolonged interaction of GRB7 with ErbB2 and increased association of ErbB2 with a beta1-integrin-rich complex, which depended on GRB7 SH2 domain interactions. Finally, suppression of PTPalpha resulted in increased phosphorylation of focal adhesion kinase on Tyr-407, which induced the recruitment of vinculin and the formation of a novel focal adhesion kinase complex in response to ErbB2 activation in mammary epithelial cells. Collectively, these results reveal a new role for PTPalpha in the regulation of motility of mammary epithelial cells in response to ErbB2 activation. PMID- 24217253 TI - Biochemical and functional characterization of the klotho-VS polymorphism implicated in aging and disease risk. AB - Klotho (KL) is an age-regulating protein named after the Greek goddess who spins the thread of life. Mice deficient in KL are normal throughout development, but rapidly degenerate and display a variety of aging-associated abnormalities that eventually lead to decreased life expectancy. While multiple genetic association studies have identified KL polymorphisms linked with changes in disease risk, there is a paucity of concrete mechanistic data to explain how these amino acid substitutions alter KL protein function. The KLVS polymorphism is suggested to lead to changes in protein trafficking although the mechanism is unclear. Our studies have sought to further investigate the functional differences in the KLVS variant that result in increased risk of many age-related diseases. Our findings suggest that the F352V and C370S substitutions lead to alterations in processing as seen by differences in shedding and half-life. Their co-expression in KLVS results in a phenotype resembling wild-type, but despite this intragenic complementation there are still changes in homodimerization and interactions with FGFR1c. Taken together, these studies suggest that KLVS leads to altered homodimerization that indirectly leads to changes in processing and FGFR1c interactions. These findings help elucidate the functional differences that result from the VS polymorphism, which will help clarify how alterations in KL function can lead to human disease and affect cognition and lifespan. PMID- 24217254 TI - Evidence that duplications of 22q11.2 protect against schizophrenia. AB - A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia. PMID- 24217255 TI - Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. AB - Cortical circuitry dysfunction in schizophrenia has been studied at many different levels of resolution, but not at the most basic unit of network organization--synaptic inputs. Multi-label electron or confocal light microscopy is required to examine specific types of synaptic inputs, and application of these methods to quantitatively study disease-related changes in human postmortem tissue has not been feasible for technical reasons. We recently developed a multi label confocal light microscopic approach that makes possible the systematic identification and quantification of synaptic inputs, and of the relative levels of proteins localized to these inputs, in human postmortem tissue. We applied this approach to quantify parvalbumin basket cell (PVBC) inputs in area 9 of the dorsolateral prefrontal cortex from schizophrenia and matched comparison subjects. Tissue sections were triple-labeled for the 65 kD isoform of glutamic acid decarboxylase (GAD65), PV and the GABA(A) receptor alpha1 subunit. PVBC axonal boutons were defined as PV/GAD65 dual-labeled puncta, and PVBC inputs were defined as a PVBC bouton that overlapped a GABA(A) receptor alpha1 subunit punctum. The density of PVBC inputs was unchanged in subjects with schizophrenia, but levels of PV protein were lower in PVBC boutons. In concert with prior reports, these findings indicate that PVBC dysfunction in schizophrenia reflects molecular and not structural alterations in these cells and their axon terminals. PMID- 24217257 TI - Are critical deterioration events the right metric to determine the impact of rapid response systems? PMID- 24217256 TI - Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. AB - Patients with major depressive disorder (MDD) have an increased onset risk of aging-related somatic diseases such as heart disease, diabetes, obesity and cancer. This suggests mechanisms of accelerated biological aging among the depressed, which can be indicated by a shorter length of telomeres. We examine whether MDD is associated with accelerated biological aging, and whether depression characteristics such as severity, duration, and psychoactive medication do further impact on biological aging. Data are from the Netherlands Study of Depression and Anxiety, including 1095 current MDD patients, 802 remitted MDD patients and 510 control subjects. Telomere length (TL) was assessed as the telomere sequence copy number (T) compared to a single-copy gene copy number (S) using quantitative polymerase chain reaction. This resulted in a T/S ratio and was converted to base pairs (bp). MDD diagnosis and MDD characteristics were determined by self-report questionnaires and structured psychiatric interviews. Compared with control subjects (mean bp=5541), sociodemographic adjusted TL was shorter among remitted MDD patients (mean bp=5459; P=0.014) and current MDD patients (mean bp=5461; P=0.012). Adjustment for health and lifestyle variables did not reduce the associations. Within the current MDD patients, separate analyses showed that both higher depression severity (P<0.01) and longer symptom duration in the past 4 years (P=0.01) were associated with shorter TL. Our results demonstrate that depressed patients show accelerated cellular aging according to a 'dose-response' gradient: those with the most severe and chronic MDD showed the shortest TL. We also confirmed the imprint of past exposure to depression, as those with remitted MDD had shorter TL than controls. PMID- 24217258 TI - Cardiotropic viral infection in HIV-associated cardiomyopathy: pathogen or innocent bystander? PMID- 24217259 TI - Left ventricular hypertrabeculation/non-compaction in a pregnant woman. PMID- 24217261 TI - Effects of single aortic clamping versus partial aortic clamping techniques on post-operative stroke during coronary artery bypass surgery. AB - BACKGROUND: The aim of this study was to compare the effects of single-clamping and partial-clamping techniques on postoperative stroke during coronary artery bypass surgery. METHODS: Between December 2008 and December 2012, 2 000 patients who underwent coronary artery bypass grafting in two hospitals were analysed. Post-operative neurological complications were analysed retrospectively in these patients. The cases were divided into two groups: in group 1, 1 500 patients were analysed, in whom proximal anastomosis was performed with partial clamping in a beating heart (n = 1 500, 846 male, 654 female; mean age 63.25 +/- 5.72 years; range 43-78 years). In group 2, 500 patients were analysed, in whom proximal anastomosis had been performed by other surgical teams in another hospital, with cross clamping in a resting heart with cardioplegia (n = 500, 296 male, 214 female; mean age 64.83 +/- 8.12 years; range 41-81 years). During 30 days post operatively, neurological deficits, stroke incidence and the relationship of the clinical situation to mortality were analysed. RESULTS: For both groups, patients were similar in terms of patient characteristics. In group 2, cross-clamp duration and perfusion time were longer; however, time of hospital stay was similar in the two groups. Post-operative stroke was seen in 26 patients in group 1 (1.73%) and in nine in group 2 (1.8%). The difference between the two groups was not statistically significant (p = 0.92). All stroke patients were over the age of 55 years. Seven of the stroke patients died (21.1%). In total, 31 patients died because of multiple organ failure in the postoperative 30 days (group 1: 1.6%; group 2: 1.4%) (p = 0.91). Smoking, diabetes mellitus, hypertension, atrial fibrillation, peripheral vascular disease and hypercholesterolaemia were found to be factors that affected stroke development. Mean duration of hospital stay was 5.1 +/- 2.8 days in group 1 and 4.9 +/- 3.6 days in group 2 and the difference between the two groups was not statistically significant (p = 0.46). CONCLUSION: In patients without plaques in the aorta, performing partial clamping did not increase stroke incidence. PMID- 24217260 TI - Awareness of hypertension and factors associated with uncontrolled hypertension in Sudanese adults. AB - BACKGROUND: The incidence of hypertension (HTN) has increased rapidly in the Sudan in the last few years. The aim of this study was to determine the prevalence of uncontrolled HTN and the risk factors associated with it in Sudanese adults. METHODS: This study was cross sectional. Data were collected using structured questionnaires filled in during interviews with subjects visiting referral clinics in Khartoum, the capital city of Sudan. Blood pressure (BP) was measured using a digital sphygmomanometer. A digital balance was used for determination of body weight and a traditional cloth tape measure was used for measuring height, for calculation of body mass index. RESULTS: This study included 200 subjects, 46% male and 54% female. In the whole study, 82% of subjects (p < 0.001) were on hypertension drug treatment. Of these, 64% had their BP controlled to normal standards set by the World Health Organistion (< 140/90 mmHg). The prevalence of uncontrolled BP was significantly (p < 0.001) higher in males (61%) compared to females (15%). When the risk factors of HTN were considered, 54% of the subjects had a positive family history of HTN and 52% were smokers. Uncontrolled BP was found to be significantly (p < 0.001) higher in smoking males (43%) compared to females (4%). It was also high in people with higher education (55%) and workers (41%). In these groups, when genders were considered separately, uncontrolled hypertension was significantly (p < 0.01) higher in males than females with higher education (67 and 40%, respectively), and in workers (86 and 10%, respectively). Uncontrolled HTN was associated with overweight and obesity in 45 and 29% of the subjects, respectively. Most of the interviewed subjects were not aware of the consequences of HTN and its associated risk factors. CONCLUSION: Uncontrolled HTN was associated with risk factors of HTN and lifestyle, and was more prominent in the male gender. The ignorance of the interviewed subjects about HTN, its associated risk factors, changes in lifestyle and adherence to taking the medication may have been a major factor in the prevalence of uncontrolled HTN. PMID- 24217262 TI - Ventilation during cardiopulmonary bypass did not attenuate inflammatory response or affect postoperative outcomes. AB - INTRODUCTION: Cardiopulmonary bypass causes a series of inflammatory events that have adverse effects on the outcome. The release of cytokines, including interleukins, plays a key role in the pathophysiology of the process. Simultaneously, cessation of ventilation and pulmonary blood flow contribute to ischaemia-reperfusion injury in the lungs when reperfusion is maintained. Collapse of the lungs during cardiopulmonary bypass leads to postoperative atelectasis, which correlates with the amount of intrapulmonary shunt. Atelectasis also causes post-perfusion lung injury. In this study, we aimed to document the effects of continued low-frequency ventilation on the inflammatory response following cardiopulmonary bypass and on outcomes, particularly pulmonary function. METHODS: Fifty-nine patients subjected to elective coronary bypass surgery were prospectively randomised to two groups, continuous ventilation (5 ml/kg tidal volume, 5/min frequency, zero end-expiratory pressure) and no ventilation, during cardiopulmonary bypass. Serum interleukins 6, 8 and 10 (as inflammatory markers), and serum lactate (as a marker for pulmonary injury) levels were studied, and alveolar- arterial oxygen gradient measurements were made after the induction of anaesthesia, and immediately, one and six hours after the discontinuation of cardiopulmonary bypass. RESULTS: There were 29 patients in the non-ventilated and 30 in the continuously ventilated groups. The pre operative demographics and intra-operative characteristics of the patients were comparable. The serum levels of interleukin 6 (IL-6) increased with time, and levels were higher in the nonventilated group only immediately after discontinuation of cardiopulmonary bypass. IL-8 levels significantly increased only in the non-ventilated group, but the levels did not differ between the groups. Serum levels of IL-10 and lactate also increased with time, and levels of both were higher in the non-ventilated group only immediately after the discontinuation of cardiopulmonary bypass. Alveolar-arterial oxygen gradient measurements were higher in the non-ventilated group, except for six hours after the discontinuation of cardiopulmonary bypass. The intubation time, length of stay in intensive care unit and hospital, postoperative adverse events and mortality rates were not different between the groups. CONCLUSION: Despite higher cytokine and lactate levels and alveolar-arterial oxygen gradients in specific time periods, an attenuation in the inflammatory response following cardiopulmonary bypass due to low-frequency, low-tidal volume ventilation could not be documented. Clinical parameters concerning pulmonary and other major system functions and occurrence of postoperative adverse events were not affected by continuous ventilation. PMID- 24217263 TI - Long QT syndrome in South Africa: the results of comprehensive genetic screening. AB - Congenital long QT syndrome (cLQTS) is a genetic disorder predisposing to ventricular arrhythmia, syncope and sudden death. Over 700 different cLQTS causing mutations in 13 genes are known. The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening). Fourteen disease-causing mutations were identified, eight (including the founder mutation) in KCNQ1, five in KCNH2 and one in KCNE1. Two mutations were novel. Two double heterozygotes were found among the 23 families (8.5%) carrying the founder mutation. In conclusion, cLQTS in South Africa reflects both a strong founder effect and a genetic spectrum similar to that seen in other populations. Consequently, five-gene screening should be offered as a standard screening option, as is the case internationally. This will disclose compound and double heterozygotes. Fivegene screening will most likely be even more informative in other South African sub-populations with a greater genetic diversity. PMID- 24217264 TI - Gender and ethnic differences in the control of hyperlipidaemia and other vascular risk factors: insights from the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) study. AB - AIM: The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipid-lowering drugs (LLDs) in urban patients of different ethnicity with hyperlipidaemia, and to identify possible patient characteristics associated with failure to achieve low-density lipoprotein cholesterol (LDL-C) targets. There is little published data on LDL-C attainment from developing countries. METHOD: The survey was conducted in 69 study centres in South Africa and recruited consecutive patients who had been prescribed LLDs for at least three months with no dose adjustment for six weeks. All patients provided written consent. One visit was scheduled for data collection, including fasting lipid and glucose, and HbA1c levels. RESULTS: Of the 3 001 patients recruited, 2 996 were included in the final analyses; 1 385 subjects were of Caucasian origin (818 male), 510 of African ancestry (168 male), 481 of mixed ancestry (222 male) and 620 of Asian origin (364 male). Only 60.5% of patients on LLDs for at least three months achieved the LDL-C targets recommended by the NCEP ATP III/2004 updated NCEP ATP III guidelines and 52.3% the fourth JETF/South African guidelines. African females were on average younger than females of other ethnic origins, and had the lowest smoking rates but the highest prevalence of obesity, hypertension, the metabolic syndrome and diabetes mellitus (DM), with the worst glycaemic control. Although women were less likely than men to reach goal [OR 0.65 (CI 0.54 0.77), p < 0.001 for NCEP ATP III guidelines and OR 0.76 (CI 0.64-0.91), p < 0.003 for fourth JETF guidelines], women of African ancestry were just as likely not to reach goal as their Caucasian counterparts. CONCLUSION: The results of this survey highlight the sub-optimal lipid control achieved in many South African patients, and profile important gender and ethnic differences. Control of cardiovascular disease risk factors across gender and ethnic groups remains poor. PMID- 24217265 TI - Anticoagulation: 'putting new evidence into clinical practice'. PMID- 24217267 TI - Genetics: KSR2 mutations affect energy balance, insulin sensitivity and cellular fuel oxidation. PMID- 24217268 TI - Technology: Let there be light: new implantable hydrogels for in vivo optical sensing and therapy. PMID- 24217269 TI - Central venous catheters. PMID- 24217270 TI - Leptin and ghrelin levels in children before and after adenoidectomy or adenotonsillectomy. AB - BACKGROUND AND AIM: Accelerated weight gain after (adeno)tonsillectomy has been reported in a number of studies. Whether (adeno)tonsillectomy is also a risk factor for development of overweight is unknown. We investigated serum leptin and plasma ghrelin levels before and 1 year after (adeno)tonsillectomy operation in children. MATERIALS AND METHODS: We studied 31 patients and 29 age- and sex matched healthy control children. Auxologic evaluation and biochemical investigations were performed before surgery and 1 year later. RESULTS: One year after surgery, height SDS (p = 0.001) and weight SDS (p = 0.004) were significantly increased in both groups. No changes in BMI SDS (p = 0.105) were observed. Preoperative leptin levels were significantly higher in patients than controls (p < 0.001). IGF-1, IGFBP-3, HOMA-IR and ghrelin values were not significantly different between the groups. One year after surgery, IGF-1 (p = 0.001) and IGFBP-3 (p = 0.001) were significantly increased, while ghrelin (p < 0.001) was significantly decreased. Postoperative leptin levels of patients were also significantly higher than preoperative values (p = 0.036). CONCLUSION: Significantly higher leptin levels in patients compared to control both before and 1 year after an obstruction-relieving surgery suggested that higher levels might be due to leptin resistance in these patients. Based on our findings we recommend measurement of leptin levels longitudinally for at least 5 years after adenotonsillectomy. PMID- 24217271 TI - Highly active PtAu alloy nanoparticle catalysts for the reduction of 4 nitrophenol. AB - To enhance the catalytic activity of gold nanoparticles (AuNPs) for the hydrogenation of nitro-aromatic chemicals, Pt was introduced into AuNPs to form "bare" PtAu alloy NPs using a physical approach, pulsed laser ablation in liquid (PLAL), on single metal-mixture targets. These PLAL-NPs are deemed to favor catalysis due to the absence of any surfactant molecules on their unique "bare and clean" surface. The PLAL-NPs were facilely assembled onto CeO2 nanotubes (NTs) by simply mixing them without conducting any surface functionalization, representing another advantage of these NPs. Their catalytic activity was assessed in 4-nitrophenol (4-NP) hydrogenation. The reaction catalyzed by alloy NP/CeO2-NT catalysts demonstrates a remarkably higher reaction rate in comparison with that catalyzed by pure Au and Pt NPs, and other similar Au and Pt containing catalysts reported recently. A "volcano-like" catalytic activity dependence of the alloy NPs on their chemical composition suggests a strong synergistic effect between Au and Pt in the 4-NP reduction, far beyond the simple sum of their individual contributions. It leads to the significantly enhanced catalytic activity of Pt30Au70 and Pt50Au50 alloy NPs, outperforming not only each single constituent, but also their physical mixtures and most recently reported AuNP based nanocatalysts. The favorable d-band center shift of Pt after alloying, and co-operative actions between Pt clusters and nearby Au (or mixed PtAu) sites were proposed as possible mechanisms to explain such a strong synergistic effect on catalysis. PMID- 24217272 TI - Reduced levels of mitochondrial complex I subunit NDUFB8 and linked complex I + III oxidoreductase activity in the TgCRND8 mouse model of Alzheimer's disease. AB - Bioenergetic failure is a feature of Alzheimer's disease (AD). We examined mitochondrial function in the amyloid-beta protein precursor transgenic 'TgCRND8' mouse model of AD. Activities of NADH: cytochrome c reductase (complex I + III) and cytochrome oxidase (complex IV) of the electron transport chain, as well as those of alpha-ketoglutarate dehydrogenase (alpha-KGDH) and pyruvate dehydrogenase (PDH) were assessed in brains of 45 week-old mice. Complex I + III activity was reduced by almost 50%, whereas complex IV, alpha-KGDH, and PDH activities were unaffected. Reduced activity coincided with decreased expression of NDUFB8, a nuclear-DNA encoded subunit integral to the assembly of complex I. The composition and availability of cardiolipin, a major phospholipid in inner mitochondrial membranes, was not altered. To determine whether mitochondrial output is affected by the selective reduction in complex I + III activity, we examined tissue levels of high-energy phosphates. ATP was maintained whereas creatine increased in the cortex and hippocampus. These results suggest disruption of complex I function and the likely role of creatine in sustaining ATP at late stages of dysfunction in TgCRND8 mice. PMID- 24217273 TI - Discrepancies regarding the quality of life of patients with Alzheimer's disease: a three-year longitudinal study. AB - Cross-sectional studies report notable discrepancies between patient and caregiver ratings of the quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study aimed to identify the factors associated with any changes in QoL-p ratings and any discrepancies between patient and caregiver ratings of QoL-p. Three-year follow-up of a cohort of non-institutionalized patients (n = 119). QoL-p was assessed by the Quality of Life in AD (QoL-AD) scale. We analyzed the influence of functional and cognitive status and behavioral problems in patients, and burden and mental health in caregivers. Repeated measures analysis was applied to the scores of patients and caregivers on the QoL-AD, and to the discrepancies between them. Generally, patients' own ratings remained stable over time (F3,116 = 0.9, p = 0.439), whereas caregiver ratings showed a decline (F3,116 = 9.4, p < 0.001). In the analysis of discrepancies, patients with anosognosia gave higher ratings (F1,117 = 11.9, p = 0.001), whereas caregiver ratings were lower when the patient showed greater agitation (F1,117 = 13.0, p < 0.001), apathy (F1,117 = 15.4, p < 0.001), and disabilities (F1,117 = 17.1, p < 0.001), and when the caregiver experienced greater burden (F1,117 = 9.0, p = 0.003) and worse mental health (F1,117 = 10.1, p = 0.003). Patient ratings of QoL-p remain generally stable over time, whereas those of caregivers show a decline, there being significant discrepancies in relation to specific patient and caregiver factors. PMID- 24217274 TI - Increased myeloperoxidase plasma levels in patients with Alzheimer's disease. AB - BACKGROUND: Increasing evidence supports the role of cardiovascular risk factors in the development of Alzheimer's disease (AD). OBJECTIVE: In the present pilot study, we investigated plasma concentrations of myeloperoxidase (MPO) and its possible association with plasma amyloid-beta (Abeta)1-42/1-40 ratio in AD patients and elderly healthy controls. METHODS: The study sample included 28 AD patients and 27 elderly individuals with a normal cognitive status as a control group. The Mini-Mental Status Examination was used to determine the global cognition. MPO, Abeta1-40, and Abeta1-42 plasma concentrations were measured by enzyme linked immunoabsorbent assays. RESULTS: AD patients showed significantly higher plasma concentrations of MPO in comparison to healthy elderly controls (AD versus healthy elderly controls (mean +/- SD): 132.8 +/- 114.8 ng/mL versus 55.0 +/- 42.6 ng/mL; p = 0.002). MPO plasma concentrations showed a significant positive correlation in the whole sample with the presence of AD (rho = 0.428, p < 0.001) and its stage (rho = 0.331; p = 0.013) as well as with plasma concentrations of Abeta1-42 (rho = 0.406; p = 0.004) and Abeta1-42/1-40 ratio (rho = 0.354; p = 0.013). In a binary logistic regression model, plasma MPO concentrations were independently associated with the presence of AD (p = 0.014). CONCLUSION: AD patients showed significantly increased plasma levels of MPO, which could be an important molecular link between atherosclerosis and AD. Further studies should evaluate whether MPO may also be a useful biomarker and potential new treatment target in AD. PMID- 24217275 TI - An intensive exercise program improves motor performances in patients with dementia: translational model of geriatric rehabilitation. AB - BACKGROUND: Translation of intensive exercise programs developed specifically for patients with dementia into clinical settings is lacking. OBJECTIVE: To determine if a progressive resistance and functional training program, previously evaluated in dementia outpatients, can be implemented in a geriatric inpatient setting in order to improve motor performances in patients with dementia. METHODS: Eligible patients in one ward of a German geriatric hospital were assigned to the intervention group (IG, n = 74) and received intensive exercise training specifically designed for patients with dementia. Patients in the second ward were observed as a control group (CG, n = 74). All patients received usual care treatment. Primary endpoints were maximal lower extremity strength measured by a leg-press device and duration of the 5-chair-stand test for functional performance. Secondary outcomes included a number of parameters for strength and function. RESULTS: The rehabilitation period averaged 18.1 +/- 6.8 days. The IG significantly improved in both primary endpoints (change: maximal strength, IG: +51.9 +/- 42.3% versus CG: +13.5 +/- 51.8%, p < 0.001; functional performance, IG: -19.2 +/- 22.3% versus CG: -3.8 +/- 32.2% s, p = 0.037). Secondary outcomes confirmed effects for strength and some, but not all, functional parameters. Interestingly, low baseline motor status, but not cognitive status, predicted positive training response. CONCLUSION: An intensive exercise program can be implemented in a geriatric rehabilitation setting to improve motor performances in patients with dementia. Results suggest that an intensification of training is feasible in the target group and substantially increases the benefits in comparison to receiving usual care exercise only. PMID- 24217276 TI - Is cholesterol and amyloid-beta stress induced CD147 expression a protective response? Evidence that extracellular cyclophilin a mediated neuroprotection is reliant on CD147. AB - The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which is regulated by sterol carrier protein, reportedly modulates amyloid-beta (Abeta), the neurotoxic peptide implicated in neuronal degeneration in Alzheimer's disease (AD). Given that high fat/cholesterol is linked to amyloid deposition in AD, we investigated if cholesterol and/or Abeta can alter CD147 expression in rat cortical neuronal cultures. Water-soluble cholesterol and Abeta42 dose-dependently increased CD147 protein expression, but reduced FL AbetaPP protein expression. Cholesterol and Abeta42 treatment also increased lactate dehydrogenase release but to varying degrees. Upregulation of CD147 expression was probably mediated by oxidative stress, as H2O2 (3 MUM) also induced CD147 protein expression in neuronal cultures. In light of these findings, we investigated if CD147 induction was cytoprotective, a compensatory response to injury, or alternatively, a cell death signal. To this end, we used recombinant adenovirus to overexpress human CD147 (in SH-SY5Y cells and primary cortical neurons), and pre-treated cultures with or without recombinant cyclophilin A (rCYPA) protein, prior to Abeta42 exposure. We showed that increased CD147 expression protected against Abeta42, only when rCYPA protein was added to neuronal cultures. Together, our findings reveal potentially important relationships between cholesterol loading, CD147 expression, Abeta toxicity, and the putative involvement of CYPA protein in neuroprotection in AD. PMID- 24217277 TI - Differentially disrupted functional connectivity in posteromedial cortical subregions in Alzheimer's disease. AB - Neuroimaging studies have demonstrated that patients with Alzheimer's disease (AD) have remarkable focal grey matter loss and hypometabolism in the posteromedial cortex (PMC), which is composed of the precuneus and posterior cingulate cortex, suggesting an important association of the PMC with AD pathophysiology. Studies have also shown that the PMC is a structurally and functionally heterogeneous structure containing various subregions with distinct connectivity profiles. However, whether these PMC subregions show differentially disrupted connectivity patterns in AD remains largely unknown. Here, we addressed this issue by collecting resting-state functional MRI data from 32 AD patients and 38 healthy controls. We automatically identified the PMC subregions using a graph-based module detection algorithm and then mapped the whole-brain functional connectivity pattern of each subregion. The functional connectivity analysis was followed by a hierarchical clustering analysis to classify each subregion. Three distinct spatial connectivity patterns were observed across the PMC subregions: the anterior dorsal zone was functionally connected with the sensorimotor cortex; the posterior dorsal zone was functionally connected with the frontoparietal cortex; and the central and ventral zones were functionally connected with the default-mode regions. Group comparison analysis revealed that all three functional systems were significantly disrupted in the AD patients compared to the controls and these disruptions were positively correlated with the patients' cognitive performance. Collectively, we showed that the subregions of the PMC exhibit differentially disrupted neuronal circuitry in AD patients, which provides new insight into the functional neuroanatomy of the human PMC and the alterations that may be relevant to disease. PMID- 24217278 TI - Jugular venous reflux and white matter abnormalities in Alzheimer's disease: a pilot study. AB - To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings. PMID- 24217279 TI - An 85-year old male with levodopa-responsive parkinsonism followed by dementia and supranuclear ophthalmoplegia caused by alzheimer-type pathology without Lewy bodies. AB - An 85-year-old man developed l-dopa responsive parkinsonism indistinguishable from Parkinson's disease and subsequent dementia, followed by supranuclear ophthalmoplegia and neck dorsiflexion at the terminal stage. Midbrain tegmentum and medial temporal lobe were atrophic on magnetic resonance imaging, while decreased blood flow was predominant in frontotemporal lobes, detected by 3D-SSP of 123I- IMP SPECT. Alzheimer-type pathology without Lewy body pathology was confirmed at autopsy. Substantia nigra showed mild degeneration and several neurofibrillary tangles without Lewy body pathology or progressive supranuclear palsy cytopathology. L-dopa responsive parkinsonism could be an initial manifestation of Alzheimer's disease, which should be included in the differential diagnosis. PMID- 24217280 TI - Increased cerebrospinal fluid tau levels in logopenic variant of Alzheimer's disease. AB - BACKGROUND: Patients with logopenic variant of primary progressive aphasia (lvPPA) display neuropathological differences from typical amnestic Alzheimer's disease (AD). OBJECTIVE: The aim of the study was to compare cerebrospinal fluid (CSF) biomarker levels between patients with lvPPA due to AD (lvPPA-AD), non logopenic forms of AD (nlAD), and amnestic mild cognitive impairment due to AD (aMCI-AD). METHODS: CSF biomarker concentrations were assessed in 124 patients divided into three groups matched for age, level of education, center, and disease duration: lvPPA-AD (n = 30), nlAD (n = 67). and aMCI-AD (n = 27). RESULTS: p-Tau181 levels were higher in the lvPPA-AD group than in the aMCI-AD group (p < 0.05). Total tau levels were higher in the lvPPA-AD group versus those in the nlAD (p < 0.05) and aMCI-AD (p < 0.001) groups. CONCLUSIONS: These results suggest a more pronounced involvement of a taupathy in lvPPA-AD compared to aMCI AD and a more important neuronal death in lvPPA-AD than in nlAD or aMCI-AD. PMID- 24217281 TI - Associations between lifestyle and cognitive function over time in women aged 40 79 years. AB - BACKGROUND: Smoking, excessive drinking, and physical inactivity are associated with reduced cognitive function but the independence, domain specific cognitive effects, and trajectories of these associations are not firmly established. OBJECTIVE: Our aim was to examine these lifestyle-cognitive function associations in middle-to-older aged women across time. METHODS: Cohort study design with repeat surveys (2001, 2005, and 2008). Participants were volunteers from a random sample of Australian women on the Brisbane electoral roll; mean (+/-SD) age 60 +/ 11 years in 2001. Outcome measures were the Mini-Mental State Examination (MMSE), Auditory Delayed Index (ADI), Visual Delayed Index (VDI), Working Memory Index (WMI), and Processing Speed Index (PSI). RESULTS: 489 women completed cognitive testing in 2001, 451 in 2005, and 376 in 2008. Mean (+/-SD) cognitive scores in 2001 were MMSE: 29.1 +/- 1.2, ADI: 104.6 +/- 13.4, VDI: 107.2 +/- 14.0, WMI: 104.1 +/- 12.3, and PSI: 102.7 +/- 11.8. Multivariate adjusted mean scores (95% CI) over the 7-year study period were higher for moderate drinkers than non drinkers for the MMSE (beta = 0.32; 0.04, 0.61), the VDI (beta = 4.33; 0.96, 7.70), and the WMI (beta = 3.21; 0.34, 6.07). Current smokers performed worse than never-smokers for the MMSE (beta = -0.35; 0.64, -0.06), the VDI (beta = 3.91; -7.57, -0.26), the WMI (beta = -3.42; -6.67, -0.18), and the PSI (beta = 5.89; -8.91, -2.87). PSI was higher in women performing strenuous physical activity compared to inactive women (beta = 2.14; 0.37, 3.90). None of the three lifestyle parameters influenced the changes in cognition across time. CONCLUSIONS: Alcohol and exercise were associated with selective protective effects and tobacco with selective harmful effects on cognitive function in middle-to-older aged women. Associations remained consistent across time. PMID- 24217282 TI - Pharmacodynamics of cholinesterase inhibitors suggests add-on therapy with a low dose carbamylating inhibitor in patients on long-term treatment with rapidly reversible inhibitors. AB - Despite three decades of intensive research in the field of Alzheimer's disease (AD) and numerous clinical trials of new therapeutic agents, cholinesterase inhibitors (ChEIs) are still the mainstay of therapeutics for AD and dementia with Lewy bodies. Pharmacodynamic analyses of ChEIs provide paradoxical observations. Treatment with the rapidly reversible, noncarbamylating ChEIs (donepezil, galantamine, and tacrine) increases acetylcholinesterase (AChE) protein expression, whereas the carbamylating agent, rivastigmine, produces sustained inhibition with no significant change in AChE protein expression. Still, the symptomatic clinical efficacies of all these agents are similar. We report here for the first time that treatment with phenserine, another carbamylating ChEI, produces a sustained but mild inhibition of AChE in cerebrospinal fluid (CSF) of AD patients. We also show that phenserine treatment reverses donepezil-induced elevation of AChE expression. Further analyses on CSF of another larger patient cohort treated with donepezil revealed that, in addition to its main mode of action, donepezil produced two other pharmacodynamics with potentially contradictory outcomes. Donepezil-induced AChE expression favored an AChE-driven amyloid-beta peptide (Abeta) aggregation, whereas donepezil itself concentration-dependently counteracted the AChE-induced Abeta aggregation, most likely by competing with the Abeta peptides for peripheral anionic site on the AChE protein. The reduction of AChE protein expression in the donepezil-treated patients by concomitant administration of the carbamylating agent, phenserine, could allow the donepezil molecule to only prevent interaction between Abeta and AChE. The current study suggests that an add-on therapy with a low-dose formulation of a carbamylating agent in patients on long-term donepezil treatment should be explored as a strategy for enhancing the clinical efficacy of these agents in dementia disorders. PMID- 24217284 TI - Synthesis and structural characterisation of Pd(II) and Pt(II) complexes with a flexible, ferrocene-based P,S-donor amidophosphine ligand. AB - 1'-Diphenylphosphino-1-{[(2-(methylthio)ethyl)amino]carbonyl}ferrocene (1), accessible via amidation of 1'-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) with 2-(methylthio)ethylamine, reacts with [PdCl2(cod)] (cod = cycloocta 1,5-diene) at a 1 : 1 metal-to-ligand ratio to give trans-[PdCl2(1-kappa(2)P,S)] (trans-2) as the sole product. A similar reaction with [PtCl2(cod)] affords a mixture of cis- and trans-[PtCl2(1-kappa(2)P,S)] (cis- and trans-3), which can be separated by fractional crystallisation. Complexation reactions performed with 2 equiv. of the ligand are less selective, yielding mixtures of the expected bis phosphine complexes (i.e., trans-[PdCl2(1-kappaP)2], or a mixture of cis- and trans-[PtCl2(-kappaP)2]) with the respective monophosphine complexes. The structures of 1, trans-2, cis-3 and trans-3 determined by X-ray diffraction demonstrate the ability of the title ligand to act as a flexible cis- or trans P,S-chelate donor (the ligand bite angles are 174.03(2)/173.05(2) degrees for trans-2/3 and 92.86(2) degrees for cis-3). PMID- 24217283 TI - Differential expression of conserved germ line markers and delayed segregation of male and female primordial germ cells in a hermaphrodite, the leech helobdella. AB - In sexually reproducing animals, primordial germ cells (PGCs) are often set aside early in embryogenesis, a strategy that minimizes the risk of genomic damage associated with replication and mitosis during the cell cycle. Here, we have used germ line markers (piwi, vasa, and nanos) and microinjected cell lineage tracers to show that PGC specification in the leech genus Helobdella follows a different scenario: in this hermaphrodite, the male and female PGCs segregate from somatic lineages only after more than 20 rounds of zygotic mitosis; the male and female PGCs share the same (mesodermal) cell lineage for 19 rounds of zygotic mitosis. Moreover, while all three markers are expressed in both male and female reproductive tissues of the adult, they are expressed differentially between the male and female PGCs of the developing embryo: piwi and vasa are expressed preferentially in female PGCs at a time when nanos is expressed preferentially in male PGCs. A priori, the delayed segregation of male and female PGCs from somatic tissues and from one another increases the probability of mutations affecting both male and female PGCs of a given individual. We speculate that this suite of features, combined with a capacity for self-fertilization, may contribute to the dramatically rearranged genome of Helobdella robusta relative to other animals. PMID- 24217285 TI - Crambescidin-816 acts as a fungicidal with more potency than crambescidin-800 and -830, inducing cell cycle arrest, increased cell size and apoptosis in Saccharomyces cerevisiae. AB - In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infections. PMID- 24217286 TI - Omega-3 fatty acids modulate Weibel-Palade body degranulation and actin cytoskeleton rearrangement in PMA-stimulated human umbilical vein endothelial cells. AB - Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 uM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 degrees C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibers. These findings indicate that LC n 3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs. PMID- 24217287 TI - Smenamides A and B, chlorinated peptide/polyketide hybrids containing a dolapyrrolidinone unit from the Caribbean sponge Smenospongia aurea. Evaluation of their role as leads in antitumor drug research. AB - An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design. PMID- 24217288 TI - A target-oriented algorithm for citrate-calcium anticoagulation in clinical practice. AB - BACKGROUND/AIMS: Because of a high monitoring demand and an ensuing need for automation of regional citrate anticoagulation (RCA), a new semi-automated target oriented algorithm was developed. The aim of this study was the evaluation of its functionality and safety. METHODS: Fourteen haemodialysis patients were treated 5 times consecutively with RCA. Samples were drawn pre- and post-infusion once per hour. Electrolytes, blood cell counts, acid-base and coagulation parameters were analyzed. RESULTS: Mean ionized calcium (Ca(2+)) values pre-filter were 0.23 and 0.33 mmol/l in the 0.2 and 0.3 mmol/l target groups, respectively. Extraction ratios for citrate and total calcium through the dialysis filter were constant during the entire treatment (83 and 68%, respectively). Citrate accumulation was avoided. CONCLUSION: The new algorithm enables safe and accurate RCA. By regulating Ca(2+) pre-filter using the target-oriented algorithm, the degree of anticoagulation may be easily controlled. PMID- 24217289 TI - Improving clinical trial recruitment: experience of a tertiary renal oncology centre. PMID- 24217290 TI - Special topic: educational theory and practice. PMID- 24217291 TI - Label-free and ultrasensitive fluorescence detection of cocaine based on a strategy that utilizes DNA-templated silver nanoclusters and the nicking endonuclease-assisted signal amplification method. AB - A general and reliable strategy for the detection of cocaine was proposed utilizing DNA-templated silver nanoclusters as signal indicators and the nicking endonuclease-assisted signal amplification method. This strategy can detect cocaine specifically with a detection limit as low as 2 nM by using a small volume of 5 MUL. PMID- 24217292 TI - Long-term efficacy of pneumatic dilation and esophageal stenting for the treatment of achalasia. AB - AIMS: To compare the efficacy and safety of pneumatic dilation with stenting for the treatment of achalasia. METHODS: Achalasia patients treated with pneumatic dilation or stenting were included in this analysis. Clinical symptoms were assessed by the Eckardt score. An esophagram and esophageal manometry were performed at the pretreatment and posttreatment follow-up visits. Data such as patient demographics and complications were collected. A drop in the Eckardt score to <=3 was defined as treatment success. RESULTS: There were 151 patients treated with pneumatic dilation (n = 76) or stenting (n = 75). The 1-, 12- and 24 month therapeutic success rates were 100, 92 and 79%, respectively, in the dilation group and 100, 93 and 87%, respectively, in the stenting group. The decrease of Eckardt score in the stenting group was significantly notable (p < 0.05) compared to that of the dilation group at the long-term follow-up visits. The maximum esophageal diameter was comparable at baseline and became statistically significant [25 mm (22-30) vs. 22 mm (19-27), p = 0.004] at posttreatment month 24. The recurrence rate was 21% in the dilation group and 13% in the stenting group. The complications of either treatment were usually mild, transient and statistically insignificant. CONCLUSION: Esophageal stenting had a comparable short-term but better long-term efficacy in comparison with pneumatic dilation. PMID- 24217294 TI - Primary aneurysmal bone cyst of the distal tibial epiphysis: a case report. AB - Aneurysmal bone cyst (ABC) is a benign lesion that commonly involves the metaphysis or metadiaphyseal region of long bones in children. The WHO defined ABC as an expansile osteolytic lesion consisting of blood-filled spaces and channels that are divided by connective tissue septa that may contain osteoid tissue and osteoclast-like giant cells. ABCs are usually treated with intralesional procedures, and variables including surgeon technique, young patient, juxtaphyseal tumors, and tumor location have been associated with recurrence. Juxtaphyseal lesions breaching the physis have been described. There is only one case of primary ABC of the epiphysis in the literature. We present a second case in a 13-year-old boy who presented with a primary ABC of the distal tibial epiphysis, including diagnostic evaluation and treatment. PMID- 24217293 TI - Correlation of fundus fluorescein angiography and spectral-domain optical coherence tomography in identification of membrane subtypes in neovascular age related macular degeneration. AB - AIMS: To assess the sensitivity and specificity of spectral-domain optical coherence tomography (SDOCT) for the determination of choroidal neovascularization (CNV) subtypes in neovascular age-related macular degeneration (AMD) compared to fundus fluorescein angiography (FFA) and also the agreement between the two procedures. DESIGN: This was a retrospective, observational study. METHODS: We evaluated and compared the CNV subtypes on FFA and OCT in 100 eyes initiated on ranibizumab for neovascular AMD. RESULTS: SDOCT showed high sensitivity (85.7-98.3%) and specificity (84.2-100%) compared to FFA in the diagnosis of the CNV subtype. The area under the receiver-operating characteristic curve ranged from 0.9 to 0.93 (p value <0.0001) for the different CNV subtypes. Weighted kappa statistics showed a near-perfect agreement of 0.85 between the procedures. CONCLUSION: SDOCT is a reliable tool for the diagnosis of CNV subtypes in neovascular AMD obviating the need for an invasive procedure such as FFA. PMID- 24217295 TI - Impact of rapid response system implementation on critical deterioration events in children. AB - IMPORTANCE: Rapid response systems aim to identify and rescue deteriorating hospitalized patients. Previous pediatric rapid response system implementation studies have shown variable effectiveness in preventing rare, catastrophic outcomes such as cardiac arrest and death. OBJECTIVE: To evaluate the impact of pediatric rapid response system implementation inclusive of a medical emergency team and an early warning score on critical deterioration, a proximate outcome defined as unplanned transfer to the intensive care unit with noninvasive or invasive mechanical ventilation or vasopressor infusion in the 12 hours after transfer. DESIGN, SETTING, AND PARTICIPANTS: Quasi-experimental study with interrupted time series analysis using piecewise regression. At an urban, tertiary care children's hospital in the United States, we evaluated 1810 unplanned transfers from the general medical and surgical wards to the pediatric and neonatal intensive care units that occurred during 370,504 non-intensive care patient-days between July 1, 2007, and May 31, 2012. INTERVENTIONS: Implementation of a hospital-wide rapid response system inclusive of a medical emergency team and an early warning score in February 2010. MAIN OUTCOMES AND MEASURES: Rate of critical deterioration events, adjusted for season, ward, and case mix. RESULTS: Rapid response system implementation was associated with a significant downward change in the preintervention trajectory of critical deterioration and a 62% net decrease relative to the preintervention trend (adjusted incidence rate ratio = 0.38; 95% CI, 0.20-0.75). We observed absolute reductions in ward cardiac arrests (from 0.03 to 0.01 per 1000 non-intensive care patient-days) and deaths during ward emergencies (from 0.01 to 0.00 per 1000 non intensive care patient-days), but these were not statistically significant (P = .21 and P = .99, respectively). Among all unplanned transfers, critical deterioration was associated with a 4.97-fold increased risk of death (95% CI, 3.33-7.40; P < .001). CONCLUSIONS AND RELEVANCE: Rapid response system implementation reversed an increasing trend of critical deterioration. Cardiac arrest and death were extremely rare at baseline, and their reductions were not statistically significant despite using nearly 5 years of data. Hospitals seeking to measure rapid response system performance may consider using valid proximate outcomes like critical deterioration in addition to rare, catastrophic outcomes. PMID- 24217296 TI - Height gain in Ullrich-Turner syndrome after early and late growth hormone treatment start: results from a large retrospective German study and potential basis for an individualized treatment approach. AB - BACKGROUND: Ullrich-Turner syndrome (UTS) girls often present with short stature in adolescence to the endocrinologist when the efficacy of growth hormone (GH) to improve growth remains unknown and parameters to estimate individual GH responsiveness have yet to be determined. OBJECTIVE: Retrospective evaluation of adult height (AH) and predicted adult height at GH start (descriptive model of Ranke, Model PredAH) in early and late GH-treated German UTS patients. SUBJECTS/METHODS: 313 patients treated with GH, early [chronological age (CA) at GH start <12 years, n = 259] or late (CA at GH start >=12 years, n = 54) who reached AH were selected from KIGS (Pfizer International Growth Database). RESULTS: AH (152.5 +/- 5.9 vs. 151.1 +/- 5.4 cm, p = n.s.) after GH treatment for 7.5 +/- 2.12 years (GH start early) and for 5.2 +/- 1.2 years (GH start late) were similar (p = n.s.) as Model PredAH (155.7 +/- 4.8 vs. 154.7 +/- 4.8 cm; p = n.s.) but higher (p < 0.001) than projected adult height (Ranke, ProjAH; 148.2 +/ 5.5 vs. 145.2 +/- 6.7 cm; p = 0.001). Total height gain over ProjAH was 4.3 +/- 4.6 cm (GH start early) and 5.8 +/- 4.7 cm (GH start late, p = 0.021), respectively. CONCLUSIONS: GH may improve AH in UTS patients even when started late. The individual growth response could be estimated by the descriptive Model PredAH independent of age at treatment start. PMID- 24217297 TI - Cell size control is sirtuin(ly) exciting. PMID- 24217298 TI - A pharmaco-epistasis strategy reveals a new cell size controlling pathway in yeast. AB - Cell size is a complex quantitative trait resulting from interactions between intricate genetic networks and environmental conditions. Here, taking advantage of previous studies that uncovered hundreds of genes affecting budding yeast cell size homeostasis, we performed a wide pharmaco-epistasis analysis using drugs mimicking cell size mutations. Simple epistasis relationship emerging from this approach allowed us to characterize a new cell size homeostasis pathway comprising the sirtuin Sir2, downstream effectors including the large ribosomal subunit (60S) and the transcriptional regulators Swi4 and Swi6. We showed that this Sir2/60S signaling route acts independently of other previously described cell size controlling pathways and may integrate the metabolic status of the cell through NAD(+) intracellular concentration. Finally, although Sir2 and the 60S subunits regulate both cell size and replicative aging, we found that there is no clear causal relationship between these two complex traits. This study sheds light on a pathway of >50 genes and illustrates how pharmaco-epistasis applied to yeast offers a potent experimental framework to explore complex genotype/phenotype relationships. PMID- 24217299 TI - Analysis of mortality in low-risk patients undergoing coronary artery bypass grafting. AB - AIM: The aims of this study were to determine the early mortality rate in low risk coronary artery bypass graft (CABG) patients and examine the causes of death, to identify problems that could be avoided in future surgeries. METHODS: All low-risk patients (EuroSCORE <= 2) who died after CABG were included. Their peri-operative information was meticulously studied by internal and independent external reviewers to identify causes of death, which were classified as: cardiac or non-cardiac; and a further division as: (1) non-preventable, (2) preventable (technical error), and (3) preventable (system error). RESULTS: Early mortality was 0.93% (24/2570). Eleven patients (45.8%) were classified as preventable deaths. In six of them the main problem was identified as graft thrombosis, which was secondary to a technical error of either the harvesting or anastomosis of the left internal mammarian artery. There were also five system errors identified as delays in the treatment of an identified and potentially reversible problem. CONCLUSION: Correction of technical and system errors, such as harvesting of the left internal mammarian artery, haemostasis during surgery, and establishing standard protocols for the transfer of patients from ward to intensive care units will eventually lead to improvement in both the quality of care and patient outcomes, even in low-risk groups. PMID- 24217300 TI - A retrospective analysis of factors influencing re-operation in patients undergoing mechanical valve replacement. AB - BACKGROUND: We aimed to determine the possible factors leading to re-operation in patients undergoing mechanical valve replacement and to investigate the relationship between valvular thrombus formation and mean platelet volume. METHODS: The medical records of 43 patients with mechanical valve implantation, who were admitted to the Department of Cardiovascular Surgery of Dr Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital between 2000 and 2005 were analysed retrospectively. Data recorded included demographic characteristics, valve type, size and location, implantation position, warfarin use, INR level, additional cardiac intervention, presence of left atrial thrombus, valvular thrombus, pannus formation, perivalvular leak, left atrial aneurysm, platelet count and mean platelet volume (MPV), bleeding after the primary surgery and/or revision of surgery due to other reasons, valve protection, aortic root expansion, presence of valve calcification and infective endocarditis, pre- and postoperative rhythm pattern, brand name of prosthesis, distance of the patient's house from a cardiac surgery centre, and concomitant noncardiac systemic diseases. RESULTS: Mean age was 49.3 years (range 19-78 years). Of the patients, 51% (n = 22) were males and 49% (n = 21) were females. The re-operation mortality was 11.6%. Age, gender, valve type, brand of valve prosthesis, and implantation position were not risk factors for re-operation. The MPV was higher and statistically significant in patients with valvular thrombus during re-operation (p < 0.001). MPV was determined to be an independent risk factor with 85% sensitivity and 87% specificity. CONCLUSION: MPV and INR levels should be closely monitored when designing individualised postoperative medical treatment for patients undergoing heart valve re-operation. PMID- 24217301 TI - Does vitamin C or its combination with vitamin E improve radial artery endothelium-dependent vasodilatation in patients awaiting coronary artery bypass surgery? AB - BACKGROUND: We evaluated the vasodilatory effects of two antioxidants, vitamins C (ascorbic acid) and E (alpha-tocopherol), on radial artery and endothelium dependent responses in patients awaiting coronary artery bypass surgery. METHODS: The study was performed in three groups. The first group took 2 g of vitamin C orally (n = 31, vitamin C group), the second group took 2 g of vitamin C with 600 mg of vitamin E orally (n = 31, vitamins C + E group), and the third group took no medication (n = 31, control group). After baseline measurements were taken of the radial artery lumen diameter, flow volume and lumen area in the non-dominant radial artery, occlusion was maintained for five minutes with a pressure cuff placed around the arm. The measurements were taken again at the time of deflating the cuff, and 60 seconds later. The measurements were repeated after medication in two of the groups and after placebo in the third group. RESULTS: We compared values of the vitamin C group with those of the vitamins C + E group, and found that the latter were higher than those of the vitamin C group but not statistically significant. In the control group, there was no statistical difference. CONCLUSION: Vitamin C or its combination with vitamin E significantly enhanced endothelium-dependent vasodilatation in the radial circulation of patients with coronary artery disease. Its combination with vitamin E was superior to vitamin C administration alone for endothelial enhancement but this difference was not statistically significant. We hypothesised that vitamin C or its combination with vitamin E may be used as antioxidants for arterial graft patency in patients undergoing coronary artery surgery. PMID- 24217302 TI - Effectiveness of prophylactic levosimendan in high-risk valve surgery patients. AB - OBJECTIVE: Levosimendan has anti-ischaemic effects, improves myocardial contractility and increases systemic, pulmonary and coronary vasodilatation. These properties suggest potential advantages in high-risk cardiac valve surgery patients where cardioprotection would be valuable. The present study investigated the peri-operative haemodynamic effects of prophylactic levosimendan infusion in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension. METHODS: Between May 2006 and July 2007, 20 consecutive patients with severe pulmonary arterial hypertension (systolic pulmonary artery pressure >= 60 mmHg) and/or low ejection fraction (< 50%) who underwent valve surgery in our clinic were included in the study and randomised into two groups. Levosimendan was administered to 10 patients in group I and not to the 10 patients in the control group. Cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) were recorded for each patient preoperatively and for 24 hours following the operation. RESULTS: CO and CI values were higher in the levosimendan group during the study period (p < 0.05). MPAP and PVR values were significantly lower in the levosimendan group for the 24-hour period (p < 0.05) and SVR values were significantly lower after 24 hours in both groups. When clinical results were considered, no difference in favour of levosimendan was detected regarding the mortality and morbidity rates between the groups. CONCLUSION: Levosimendan improved the haemodynamics in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension, and facilitated weaning from cardiopulmonary bypass in such high risk patients when started as a prophylactic agent. PMID- 24217303 TI - Association of homocysteinaemia with hyperglycaemia, dyslipidaemia, hypertension and obesity. AB - AIM: Hyperhomocysteinaemia and the metabolic syndrome are associated with increased cardiovascular risk. We investigated whether there is a link between the metabolic syndrome or its components and homocysteine levels in a population without cardiovascular disease. METHODS: From the population sample of 382 participants (286 females and 96 males) we isolated those reflecting the metabolic syndrome and determined their homocysteine levels. We then evaluated the association of homocysteine with hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia, hypertension and obesity, using a significance level of p = 0.05. Enzymatic methods were used for all biochemical parameters. RESULTS: We found the statistical relationship between homocysteine and the metabolic syndrome as follows: hyperglycaemia (p = 0.175), hypertriglyceridaemia (p = 0.442), hypercholesterolaemia (p = 0.480), obesity (p = 0.080); and hypertension: systolic pressure (p = 0.002) and diastolic pressure (p = 0.033). CONCLUSION: We found no statistically significant association between baseline plasma homocysteine levels and the metabolic syndrome, except for hypertension. PMID- 24217304 TI - Increased carotid intima-media thickness associated with high hs-CRP levels is a predictor of unstable coronary artery disease. AB - Increased values of carotid intima-media thickness (CIMT) and high-sensitivity C reactive protein (hs-CRP) are predictors of acute coronary events. We analysed the link between CIMT and hs-CRP in cases with coronary artery disease (CAD). From 1 January to 30 June 2012, we evaluated 43 patients with acute coronary syndrome (group A), 50 patients with stable coronary artery disease (group B) and 50 healthy volunteers (group C). All were analysed for CIMT and hs-CRP levels. CIMT values were higher in groups A and B (0.94 +/- 0.21 mm, 0.89 +/- 0.19 mm, respectively) and lower in group C (0.64 +/- 0.09 mm), and this was statistically significant (p < 0.0001). However the values of hs-CRP were higher in group A (1.87 +/- 0.36 mg/l) and lower in groups B and C (1.07 +/- 0.28 mg/l, 0.97 +/- 0.45 mg/l, respectively) and this was also statistically significant (p < 0.0001). PMID- 24217305 TI - Efficacy and safety of sirolimus-eluting stents versus bare-metal stents in coronary artery disease patients with diabetes: a meta-analysis. AB - OBJECTIVE: To compare by meta-analysis the efficacy and safety of sirolimus eluting and bare-metal stents in coronary artery disease (CAD) patients with diabetes. METHOD: PubMed, MEDLINE and EMBASE were searched from 1971 to 2012. Data on the efficacy and safety of sirolimus-eluting and bare-metal stents in patients with diabetes were collected. A meta-analysis was then performed on a total of 1 259 CAD patients with diabetes from six studies. The odds ratio (OR) was used for comparison. Subgroup analysis was performed according to the sample size, year of study, subjects' geographic area and study method. RESULTS: Compared with those in the bare-metal stent group (BMS), the subjects in the sirolimus-eluting stent (SES) group had a reduced risk for major cardiac events [OR 0.42, 95% confidence interval (CI): 024-0.74, p < 0.01] and target-lesion revascularisation (OR 0.26, 95% CI: 0.11 - 0.59, p < 0.01). There was no difference for myocardial infarction (OR 0.92, 95% CI: 0.61-1.40, p > 0.05) or mortality (OR 1.19, 95% CI: 0.74-1.92, p > 0.05). Subgroup analysis showed a significant difference for overall risk of major cardiac events between SES and BMS when the sample size was <= 90 (OR 0.28, 95% CI: 0.16-0.48, p < 0.01), when it was a randomised control trial (RCT) (OR 0.28, 95% CI: 0.19-0.42, p < 0.01), or when it was performed on European subjects (OR 0.45, 95% CI: 0.27-0.77, p < 0.01). The sensitivity was not different when one study was removed at a time. CONCLUSION: Our study confirmed that SES are safer and more effective than BMS in CAD patients with diabetes, as far as major cardiac events are concerned. PMID- 24217306 TI - Prevalence and significance of early repolarisation in a black African population: data of 246 individuals with cardiovascular morbidity. AB - BACKGROUND: Early repolarisation (ER) is commonly seen on electrocardiograms (ECG). Recent reports have described the relationship between ER and sudden cardiac death (SCD). The prevalence and significance of ER have not been studied in black Africans. METHOD: We matched clinical and ECG records of subjects over 18 years of age who consulted a cardiac unit in two medical centres of Douala, Cameroon. A questionnaire focusing on past history of syncope or family history of sudden unexplained death (SUD) was filled in by each subject. A 12-lead ECG was recorded by a trained nurse and analysed by two independent physicians. RESULTS: Of the 752 ECGs recorded, we studied 246 index cases. The mean age of subjects was 45 +/- 16 years and 53% were female. Almost 57% had hypertension, 41% had palpitations and 18% reported a history of syncope. ER pattern was found in 20% [slurring in three (3%), notching in 13% and both in three (7%)]. ER subjects were younger than those without (41 +/- 16 vs 49 +/- 16 years, p = 0.0048). Lead localisation was predominantly the laterals for the slurring pattern, whereas the inferior and lateral leads were equally involved for the notching pattern. Negative T waves in the infero-lateral leads were associated with ER (p = 0.00025). Among the subjects with syncope, 41% displayed ER and 13% did not have ER (p = 0.00014). The notching pattern seemed to be associated with syncope (p = 0.00011). CONCLUSION: Early repolarisation is frequent in black Africans, especially in the setting of cardiovascular morbidity. Early repolarisation may be associated with a past history of syncope, especially the notched pattern. PMID- 24217307 TI - Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N terminal fragment brain natriuretic peptides (NT-pro-BNP). AB - B-type natriuretic peptide (BNP) is a member of a fournatriuretic peptide family that shares a common 17-peptide ring structure. The N-terminal fragment (NT-pro BNP) is biologically inert, but both are secreted in the plasma in equimolar quantities and both have been evaluated for use in the management of congestive heart failure. BNP and NT-pro-BNP are frequently used in the diagnosis of congestive heart failure and distinguishing between patients with dyspnoea of cardiac or pulmonary origin. Values of NT-pro-BNP are affected by age or the presence of one or several co-morbidities such as chronic renal failure, type 2 diabetes, and acute coronary syndrome. 'Normal' values of these peptides also vary depending on the type of test used. The performance characteristics of these tests vary depending on the patients on whom they are used and the manufacturer. For this reason, the determination of reference values for this peptide represents such a challenge. PMID- 24217308 TI - Saxagliptin demonstrates no increased risk for cardiovascular death, heart attack or stroke in the SAVOR cardiovascular outcomes trial. PMID- 24217310 TI - On the structure of water and chloride ion interactions with a peptide backbone in solution. AB - The arrangement of water and chloride ions around a model peptide (glycyl-L prolyl-glycine-NH2) was investigated using Molecular Dynamics (MD) simulations and complementary Empirical Potential Structure Refinement (EPSR) simulations which adapt the modelled structure to reproduce experimentally measured neutron diffraction data. The results are in good qualitative agreement and show a common picture for all hydrogen-containing amine and amide groups: namely that there are two common chloride interactions observed - a direct contact between Cl(-) and peptide backbone and a water-mediated interaction. The geometry of this mediation depends on the distance between chloride and nitrogen and hints towards two distinct modes of interaction between water and the ion, either along one of the O-H bonds or along the water dipole. PMID- 24217311 TI - Graphene-NiO nanohybrid prepared by dry plasma reduction as a low-cost counter electrode material for dye-sensitized solar cells. AB - NiO nanoparticles (NPs) were hybridized on the surface of reduced graphene oxide (RGO) by dry plasma reduction (DPR) at atmospheric pressure without any toxic chemicals and at a low temperature. NiO-NPs of 0.5-3 nm size, with a typical size of 1.5 nm, were uniformly hybridized on the surface of RGO. An XPS analysis and the Raman spectra also revealed the repair of some structural damage on the basal plane of the graphene. The material when applied to the counter electrode (CE) of dye-sensitized solar cells (DSCs) exhibited a power conversion efficiency of 7.42% (+/- 0.10%), which is comparable to a conventional Pt-sputtered CE (8.18% (+/- 0.08%)). This material outperformed CEs produced using NiO-NPs (1.53% (+/- 0.15%)), GO (4.48% (+/- 0.12%)) and RGO (5.18% (+/- 0.11)) due to its high electrochemical catalytic activity and high conductivity. The charge transfer resistance for NiO-NP-RGO was as low as 1.93 Omega cm(2), while those of a NiO-NP immobilized electrode and a GO-coated electrode were 44.39 Omega cm(2) and 12.19 Omega cm(2), respectively, due to a synergistic effect. PMID- 24217312 TI - Highly efficient oxygen reduction electrocatalysts based on winged carbon nanotubes. AB - Developing electrocatalysts with both high selectivity and efficiency for the oxygen reduction reaction (ORR) is critical for several applications including fuel cells and metal-air batteries. In this work we developed high performance electrocatalysts based on unique winged carbon nanotubes. We found that the outer walls of a special type of carbon nanotubes/nanofibers, when selectively oxidized, unzipped and exfoliated, form graphene wings strongly attached to the inner tubes. After doping with nitrogen, the winged nanotubes exhibited outstanding activity toward catalyzing the ORR through the four-electron pathway with excellent stability and methanol/carbon monoxide tolerance. While the doped graphene wings with high active site density bring remarkable catalytic activity, the inner tubes remain intact and conductive to facilitate electron transport during electrocatalysis. PMID- 24217313 TI - Improvement in high-density lipoprotein cholesterol levels in argentine Indian school children after vitamin D supplementation. AB - BACKGROUND/AIMS: Low vitamin D levels correlate with dyslipidemia, but limited data exist on indigenous children. The objective was to determine whether vitamin D supplementation improves high-density lipoprotein cholesterol (HDL-C) levels among Koya children. METHODS: A prospective 1-year study evaluated a treated cohort of 70 (38 males) children aged 10.3 +/- 2.1 years who received 5,000 U of vitamin D weekly during 8 weeks, and a control group of 20 (8 males) children aged 9.2 +/- 1.1 years who did not receive vitamin D. RESULTS/CONCLUSIONS: At baseline, 18 (20%) had severe vitamin D deficiency (<10 ng/ml), 66 (73.3%) had deficiency (10 to <20 ng/ml), and 6 (6.6%) had insufficiency (20 to <30 ng/ml). At baseline, there was no significant difference in the prevalence of hypovitaminosis D between groups. After 1 year, the prevalence of severe vitamin D deficiency decreased from 20 to 0%, and that of insufficiency increased from 6 to 19% (p < 0.001) only in the treated group. The prevalence of low HDL-C also decreased in the treated group only (35.7-5.7%; p < 0.01). Multiple linear regression analysis showed that treated children improved HDL-C levels by 4 mg/dl (R(2): 0.13) adjusted for confounding factors, suggesting that vitamin D supplementation among Indian children improved HDL-C levels. PMID- 24217314 TI - ADHD symptoms and benefit from extended time testing accommodations. AB - OBJECTIVE: To investigate the relationship between ADHD symptoms, executive functioning problems, and benefit from extended time testing accommodations. METHOD: College students completed a battery of measures assessing processing speed and reading fluency, reading comprehension (under two different time limits), symptoms of ADHD, executive functioning deficits, and perceptions of need for extended time. RESULTS: Students reporting more symptoms of ADHD and executive functioning deficits actually benefited less from extended time, and students' perceptions of their timing needs did not predict benefit. CONCLUSION: Students with more ADHD symptoms are less likely to use extended time effectively, possibly because of their associated executive functioning problems. These results suggest there may be little justification for examining a student's ADHD symptoms when making extended time accommodation decisions. PMID- 24217315 TI - Gene regulation by antisense transcription. AB - Antisense transcription, which was initially considered by many as transcriptional noise, is increasingly being recognized as an important regulator of gene expression. It is widespread among all kingdoms of life and has been shown to influence - either through the act of transcription or through the non coding RNA that is produced - almost all stages of gene expression, from transcription and translation to RNA degradation. Antisense transcription can function as a fast evolving regulatory switch and a modular scaffold for protein complexes, and it can 'rewire' regulatory networks. The genomic arrangement of antisense RNAs opposite sense genes indicates that they might be part of self regulatory circuits that allow genes to regulate their own expression. PMID- 24217322 TI - Human evolution: reprogrammed cells dissect ape retrotransposition. PMID- 24217325 TI - Corncobs as a potential source of functional chemicals. AB - Phytochemical examination of corncob extracts led to the isolation of a new lignan identified as 7,7'-dihydroxy-3'-O-demethyl-4-methoxymatairesinol, together with seven known compounds, identified as beta-sitosterol, beta-sitosteryl-beta-D glucoside, 6beta-hydroxy-campest-4-en-3-one, 5alpha,8alpha-epidioxyergosta-6,22 dien-3beta-ol, tricin, kaempferol and p-coumaric acid. The isolated compounds were identified by one and two-dimensional NMR spectroscopies and mass spectrometry. PMID- 24217326 TI - Photoaffinity labeling of plasma proteins. AB - Photoaffinity labeling is a powerful technique for identifying a target protein. A high degree of labeling specificity can be achieved with this method in comparison to chemical labeling. Human serum albumin (HSA) and alpha1-acid glycoprotein (AGP) are two plasma proteins that bind a variety of endogenous and exogenous substances. The ligand binding mechanism of these two proteins is complex. Fatty acids, which are known to be transported in plasma by HSA, cause conformational changes and participate in allosteric ligand binding to HSA. HSA undergoes an N-B transition, a conformational change at alkaline pH, that has been reported to result in increased ligand binding. Attempts have been made to investigate the impact of fatty acids and the N-B transition on ligand binding in HSA using ketoprofen and flunitrazepam as photolabeling agents. Meanwhile, plasma AGP is a mixture of genetic variants of the protein. The photolabeling of AGP with flunitrazepam has been utilized to shed light on the topology of the protein ligand binding site. Furthermore, a review of photoaffinity labeling performed on other major plasma proteins will also be discussed. Using a photoreactive natural ligand as a photolabeling agent to identify target protein in the plasma would reduce non-specific labeling. PMID- 24217316 TI - A new world of Polycombs: unexpected partnerships and emerging functions. AB - Polycomb group (PcG) proteins are epigenetic repressors that are essential for the transcriptional control of cell differentiation and development. PcG-mediated repression is associated with specific post-translational histone modifications and is thought to involve both biochemical and physical modulation of chromatin structure. Recent advances show that PcG complexes comprise a multiplicity of variants and are far more biochemically diverse than previously thought. The importance of these new PcG complexes for normal development and disease, their targeting mechanisms and their shifting roles in the course of differentiation are now the subject of investigation and the focus of this Review. PMID- 24217327 TI - One-pot tandem synthesis of 2-arylquinazolines by a multicomponent cyclization reaction. AB - A series of 2-arylquinazolines have been synthesized in moderate to excellent yields by one-pot tandem reaction of (2-aminophenyl)methanols, aldehydes and ceric ammonium nitrate (CAN). The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, the method represents a simple and practical procedure to access 2-arylquinazolines. PMID- 24217328 TI - 3D-QSAR and cell wall permeability of antitubercular nitroimidazoles against Mycobacterium tuberculosis. AB - Inhibitory activities of monocyclic nitroimidazoles against Mycobacterium tuberculosis (Mtb) deazaflavin-dependent nitroreductase (DDN) were modeled by using docking, pharmacophore alignment and comparative molecular similarity indices analysis (CoMSIA) methods. A statistically significant model obtained from CoMSIA was established based on a training set using pharmacophore-based molecular alignment. The leave-one out cross-validation correlation coefficients q2 (CoMSIA) were 0.681. The CoMSIA model had a good correlation (r2(pred)/CoMSIA = 0.611) between the predicted and experimental activities against excluded test sets. The generated model suggests that electrostatic, hydrophobic and hydrogen bonding interactions all play important roles for interaction between ligands and receptors. The predicted cell wall permeability (logP(app)) for substrates with high inhibitory activity against Mtb were investigated. The distribution coefficient (logD) range was 2.41 < logD < 2.89 for the Mtb cell wall membrane permeability. The larger the polar surface area is, the better the permeability is. A larger radius of gyration (rgry) and a small fraction of rotatable bonds (f(rtob)) of these molecules leads to higher cell wall penetration ability. The information obtained from the in silico tools might be useful in the design of more potent compounds that are active against Mtb. PMID- 24217329 TI - Net improvement of correct answers to therapy questions after pubmed searches: pre/post comparison. AB - BACKGROUND: Clinicians search PubMed for answers to clinical questions although it is time consuming and not always successful. OBJECTIVE: To determine if PubMed used with its Clinical Queries feature to filter results based on study quality would improve search success (more correct answers to clinical questions related to therapy). METHODS: We invited 528 primary care physicians to participate, 143 (27.1%) consented, and 111 (21.0% of the total and 77.6% of those who consented) completed the study. Participants answered 14 yes/no therapy questions and were given 4 of these (2 originally answered correctly and 2 originally answered incorrectly) to search using either the PubMed main screen or PubMed Clinical Queries narrow therapy filter via a purpose-built system with identical search screens. Participants also picked 3 of the first 20 retrieved citations that best addressed each question. They were then asked to re-answer the original 14 questions. RESULTS: We found no statistically significant differences in the rates of correct or incorrect answers using the PubMed main screen or PubMed Clinical Queries. The rate of correct answers increased from 50.0% to 61.4% (95% CI 55.0%-67.8%) for the PubMed main screen searches and from 50.0% to 59.1% (95% CI 52.6%-65.6%) for Clinical Queries searches. These net absolute increases of 11.4% and 9.1%, respectively, included previously correct answers changing to incorrect at a rate of 9.5% (95% CI 5.6%-13.4%) for PubMed main screen searches and 9.1% (95% CI 5.3%-12.9%) for Clinical Queries searches, combined with increases in the rate of being correct of 20.5% (95% CI 15.2%-25.8%) for PubMed main screen searches and 17.7% (95% CI 12.7%-22.7%) for Clinical Queries searches. CONCLUSIONS: PubMed can assist clinicians answering clinical questions with an approximately 10% absolute rate of improvement in correct answers. This small increase includes more correct answers partially offset by a decrease in previously correct answers. PMID- 24217331 TI - Controllable and reversible hot spot formation on silver nanorod arrays. AB - Reversible hot spot formation is achieved for free-standing silver nanorod (AgNR) arrays fabricated by oblique angle deposition and modified with a hydrophilic surface coating. PMID- 24217330 TI - Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for patients with prostate cancer - EORTC QLQ-PR25. AB - OBJECTIVE: We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer QLQ-PR25 when applied to Korean prostate cancer (PC) patients. METHODS: A total of 172 patients who underwent curative radical prostatectomy (RP) with or without adjuvant androgen deprivation therapy were asked to complete the Korean version of the EORTC QLQ C30 and PR25 questionnaires 3 times (before and 3 and 6 months after RP). Psychometric evaluation of the questionnaire was conducted. RESULTS: Multitrait scaling analysis showed satisfactory construct validity in most scales except for bowel symptoms and hormonal treatment-related symptoms. Internal consistency tested by Cronbach's alpha coefficient met the 0.70 criterion for the urinary symptom, sexual activity and sexual functioning scales at the all 3 time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status, and higher hormonal treatment-related symptom scores in patients on hormonal treatment. Responsiveness to changes was in line with clinical implications over time after RP. CONCLUSIONS: Our results show that the EORTC QLQ-PR25 questionnaire has adequate levels in cross-cultural validity. The Korean version of the EORTC QLQ-PR25 is a generally reliable and robust instrument for the assessment of various QOL aspects that can be self administered to Korean PC patients undergoing RP. PMID- 24217332 TI - Metastatic castration-resistant prostate cancer: changing landscape with cabazitaxel. AB - Docetaxel is the standard first-line chemotherapy for men with metastatic castration-resistant prostate cancer. Until recently, there was no standard therapy after failure of docetaxel treatment. Cabazitaxel has been shown to improve overall survival in this setting. As a result, the treatment paradigm for mCRPC is changing rapidly. The improved survival shown with cabazitaxel provides an important new opportunity to treat men with mCRPC after docetaxel treatment. Despite the toxicity recorded in the pivotal study, subsequent trials have shown that cabazitaxel is a safe drug. Patient selection and the optimal interval between prior docetaxel treatment and cabazitaxel remain the critical issues. According to a subanalysis of the various studies discussed in this review, there is a patient profile that will probably benefit from use of cabazitaxel after docetaxel failure. Cabazitaxel represents a new treatment option for patients with prostate cancer. PMID- 24217333 TI - Exclusion of influences of ARMS2 polymorphisms on the central visual field in retinitis pigmentosa. AB - PURPOSE: To investigate the effects of polymorphisms of the age-related maculopathy susceptibility 2 (ARMS2) gene on the central visual field defects in retinitis pigmentosa (RP). SUBJECTS AND METHODS: The visual field was evaluated using the 10-2 Swedish Interactive Threshold Algorithm Fast Program and mean deviation (MD) slope, and regression coefficients of average sensitivity of the central 4 points (Cent4) were compared between each genetic subgroup. RESULTS: The MD slope (right/left) was as follows: GG, -1.37 +/- 2.18/ -0.89 +/- 1.15; GT, -0.56 +/- 1.40/-0.77 +/- 1.04; TT, -0.75 +/- 0.64/ -0.38 +/- 0.92 dB/year. The Cent4 was as follows: GG, -1.34 +/- 2.37/-1.60 +/- 3.21; GT, -1.15 +/- 2.08/1.07 +/- 1.80; TT, -1.20 +/- 0.91/-0.65 +/- 1.37 dB/year. No significant differences in the degree of progression were observed when comparing groups. CONCLUSIONS: These data suggest that polymorphisms of the ARMS2 do not modify the progression of the central field of vision in RP patients. PMID- 24217334 TI - Synthesis of rotacatenanes by the combination of Cu-mediated threading reaction and the template method: the dual role of one ligand. AB - Rotacatenanes were synthesized by the catalytic reaction using a macrocyclic phenanthroline-CuI complex followed by the installation of another ring by the template method. In this approach, the size of the ring component of the rotaxane turns out to be a very important factor for the synthesis of rotacatenanes. PMID- 24217335 TI - P-H activation of secondary phosphanes on a parent amido diiridium complex. AB - Selected secondary phosphanes (H-PR2; R = Ph, Cy, (i)Pr) smoothly react with a parent amido-bridged diiridium cyclooctadiene complex affording mixed amido/(bis)phosphido dinuclear species. A careful investigation of the reaction profile, carried out by experimental and theoretical tools, revealed that, after an initial amido/phosphido exchange, at low temperatures a second molecule of secondary phosphane adds to the dinuclear system through an oxidative addition process leading to a hydrido amido/bis(phosphido) mixed-valence complex [Ir(III)/Ir(I)]. These species rearrange above -10 degrees C into the most stable isomer that arises from a migration of the hydrido moiety to one of the =CH fragments of a coordinated cod molecule, a transformation facilitated by the formation of an intermetallic bond. Further heating of these species reductively eliminates ammonia affording bis(phosphido)-metal-metal bonded complexes. PMID- 24217336 TI - Improving maternal mental health after a child's diagnosis of autism spectrum disorder: results from a randomized clinical trial. AB - IMPORTANCE: The prevalence of psychological distress among mothers of children with autism spectrum disorder (ASD) suggests a need for interventions that address parental mental health during the critical period after the child's autism diagnosis when parents are learning to navigate the complex system of autism services. OBJECTIVE: To investigate whether a brief cognitive behavioral intervention, problem-solving education (PSE), decreases parenting stress and maternal depressive symptoms during the period immediately following a child's diagnosis of ASD. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial compared 6 sessions of PSE with usual care. Settings included an autism clinic and 6 community-based early intervention programs that primarily serve low-income families. Participants were mothers of 122 young children (mean age, 34 months) who recently received a diagnosis of ASD. Among mothers assessed for eligibility, 17.0% declined participation. We report outcomes after 3 months of follow-up (immediate postdiagnosis period). INTERVENTIONS: Problem-solving education is a brief, cognitive intervention delivered in six 30-minute individualized sessions by existing staff (early intervention programs) or research staff without formal mental health training (autism clinic). MAIN OUTCOMES AND MEASURES: Primary outcomes were parental stress and maternal depressive symptoms. RESULTS: Fifty nine mothers were randomized to receive PSE and 63 to receive usual care. The follow-up rate was 91.0%. Most intervention mothers (78.0%) received the full PSE course. At the 3-month follow-up assessment, PSE mothers were significantly less likely than those serving as controls to have clinically significant parental stress (3.8% vs 29.3%; adjusted relative risk [aRR], 0.17; 95% CI, 0.04 to 0.65). For depressive symptoms, the risk reduction in clinically significant symptoms did not reach statistical significance (5.7% vs 22.4%; aRR, 0.33; 95% CI, 0.10 to 1.08); however, the reduction in mean depressive symptoms was statistically significant (Quick Inventory of Depressive Symptomatology score, 4.6 with PSE vs 6.9 with usual care; adjusted mean difference, -1.67; 95% CI, -3.17 to -0.18). CONCLUSIONS AND RELEVANCE: The positive effects of PSE in reducing parenting stress and depressive symptoms during the critical postdiagnosis period, when parents are asked to navigate a complex service delivery system, suggest that it may have a place in clinical practice. Further work will monitor these families for a total of 9 months to determine the trajectory of outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01021384. PMID- 24217337 TI - Radiofrequency ablation of the great saphenous vein in an elderly patient with co morbid disease. AB - An 86-year-old male patient with hypertension, Parkinsonism, benign prostatic hyperplasia, cataract and chronic obstructive pulmonary disease had a history of coronary bypass surgery in two veins due to anterior myocardial infarction one year earlier. He presented with pain and feelings of paresthesia below the knee of his left leg, and had fallen twice. He had used compressions and venoprotective medication for two years and had also received physiotherapy but it had not alleviated the symptoms. He had varicose dilatations in the left leg and pigmentation and a recovered venous ulcer scar were present on the medial malleolus. The patient was classed as grade 4 according to the CEAP classification. Because there was no deficiency in the superficial femoral and popliteal veins, the patient was taken for endovenous ablation. He had no pain or sensation of heaviness in the legs on postoperative day 10, and the first, third and sixth months of check up. Endovenous ablation is a procedure that increases the quality of life and comfort in elderly patients, with minimal pain. Radiofrequency catheter procedures have proven to be more successful in patients of all age groups than procedures such as standard surgery and foam therapy. PMID- 24217338 TI - Increased leptin/adiponectin ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development. AB - BACKGROUND: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. AIMS: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. METHODS: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. RESULTS: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. CONCLUSION: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA. PMID- 24217339 TI - Charge transport properties of spin crossover systems. AB - The study of spin crossover compounds by means of theoretical or experimental approaches has provided interesting results in recent decades. The main feature of such compounds is the change in the spin state induced by many different external stimuli, i.e. temperature, light, pressure, solvent coordination and the electric field. Spin crossover systems are potentially more useful than other magnetic molecules because their switching behaviour can occur closer to room temperature, and they are thus candidates for use in spintronic devices. Here, I review the state of the art in quantum chemical approaches to the study of such systems and discuss experiments that have focused on transport properties in single-molecule, nano-objects or thin-film spin crossover systems. PMID- 24217341 TI - Meta-analysis of primary mesh augmentation as prophylactic measure to prevent incisional hernia. AB - BACKGROUND: Incisional hernia (IH) remains one of the most frequent postoperative complications after abdominal surgery. As a consequence, primary mesh augmentation (PMA), a technique to strengthen the abdominal wall, has been gaining popularity. This meta-analysis was conducted to evaluate the prophylactic effect of PMA on the incidence of IH compared to primary suture (PS). METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Randomized controlled trials (RCTs) comparing PMA and PS for closing the abdominal wall after surgery were included. RESULTS: Out of 576 papers, 5 RCTs were selected comprising 346 patients. IH occurred significantly less in the PMA group (RR 0.25, 95% CI 0.12-0.52, I(2)0%; p < 0.001). No difference could be observed with regard to wound infection (RR 0.86, 95% CI 0.39-1.91, I(2) 0%; p = 0.71) or seroma (RR 1.22, 95% CI 0.64-2.33, I(2) 0%; p = 0.55). A trend was observed for chronic pain in favor of the PS group (RR 5.95, 95% CI 0.74-48.03, I(2)0%; p = 0.09). CONCLUSION: The use of PMA for abdominal wall closure is associated with significantly lower incidence of IH compared to PS. PMID- 24217340 TI - Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci. AB - Hedgehog (Hh) signalling regulates embryonic development and adult tissue homoeostasis. Mutations of its pathway components including Suppressor of Fused (Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli protein complex occupies a central position in the vertebrate Hh signalling pathway, especially in mammals. Here structures of full-length human and Drosophila Sufu, the human Sufu-Gli complex, along with normal mode analysis and FRET measurement results, reveal that Sufu alternates between 'open' and 'closed' conformations. The 'closed' form of Sufu is stabilized by Gli binding and inhibited by Hh treatment, whereas the 'open' state of Sufu is promoted by Gli dissociation and Hh signalling. Mutations of critical interface residues disrupt the Sufu-Gli complex and prevent Sufu from repressing Gli-mediated transcription, tethering Gli in the cytoplasm and protecting Gli from the 26S proteasome mediated degradation. Our study thus provides mechanistic insight into the mutual recognition and regulation between Sufu and Gli/Ci. PMID- 24217343 TI - Efficient spin injection into silicon and the role of the Schottky barrier. AB - Implementing spin functionalities in Si, and understanding the fundamental processes of spin injection and detection, are the main challenges in spintronics. Here we demonstrate large spin polarizations at room temperature, 34% in n-type and 10% in p-type degenerate Si bands, using a narrow Schottky and a SiO2 tunnel barrier in a direct tunneling regime. Furthermore, by increasing the width of the Schottky barrier in non-degenerate p-type Si, we observed a systematic sign reversal of the Hanle signal in the low bias regime. This dramatic change in the spin injection and detection processes with increased Schottky barrier resistance may be due to a decoupling of the spins in the interface states from the bulk band of Si, yielding a transition from a direct to a localized state assisted tunneling. Our study provides a deeper insight into the spin transport phenomenon, which should be considered for electrical spin injection into any semiconductor. PMID- 24217342 TI - Impact of different operational definitions on mild cognitive impairment rate and MMSE and MoCA performance in transient ischaemic attack and stroke. AB - BACKGROUND: Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences within established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke. METHODS: Consecutive patients underwent the MMSE, MoCA and neuropsychological battery >=1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (>1, >1.5 and >2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment. RESULTS: 91 non-demented subjects completed neuropsychological testing (mean age +/- SD 69.7 +/- 11.6 years, 54 male, 49 stroke) at a mean of 3.1 +/- 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at >2 SD cut-off to 61/91 (67%) MCI-modified at >1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original. CONCLUSION: Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies. PMID- 24217344 TI - Gender-specific alterations in salivary cortisol levels in pubertal intracytoplasmic sperm injection offspring. AB - BACKGROUND: There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life. It has been proposed that suboptimal early life conditions may 'program' key endocrine systems. A disturbance of the hypothalamic-pituitary-adrenal (HPA) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism. To date, no data on cortisol levels in children conceived by intracytoplasmic sperm injection (ICSI) are available in the literature. METHODS: In this cross sectional study, salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived (SC) counterparts. RESULTS: ICSI females had lower mean salivary cortisol levels (9.0 ug/l; 95% CI 8.1-9.9) than SC females (10.6 ug/l; 95% CI 9.7-11.5; p = 0.01). This difference remained after adjusting for current characteristics, early life factors and maternal characteristics. In ICSI males, no difference in cortisol levels was found in comparison with the SC group. CONCLUSION: In our study, 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers. However, before definite conclusions can be drawn, our results should be completed by longitudinal sampling. PMID- 24217345 TI - The CVD graphene transfer procedure introduces metallic impurities which alter the graphene electrochemical properties. AB - High quality graphene films can be fabricated by chemical vapor deposition (CVD) using Ni and Cu as catalytic substrates. Such a synthesis procedure always requires a subsequent transfer process to be performed in order to eliminate the metallic substrate and transfer the graphene onto the desired surface. We show here that such a transfer process causes significant contamination of the graphene film with residual Fe and Ni metal impurities. Fe contamination derives from the use of Fe-based etching solutions to dissolve Ni (or Cu) substrates, while residual Ni (or Cu) is due to an incomplete metal substrate etching. The presence of these metallic impurities within the transferred graphene film affects tremendously its electrochemical behavior when adopted as an electrode material. PMID- 24217346 TI - IBD: Early use of anti-TNF agents might give a helping hand to paediatric patients with Crohn's disease. PMID- 24217347 TI - Cirrhotic cardiomyopathy: pathogenesis and clinical relevance. AB - Cirrhosis is known to cause alterations in the systemic haemodynamic system. Cirrhotic cardiomyopathy designates a cardiac dysfunction that includes impaired cardiac contractility with systolic and diastolic dysfunction, as well as electromechanical abnormalities in the absence of other known causes of cardiac disease. This condition is primarily revealed by inducing physical or pharmacological stress, but echocardiography is excellent at revealing diastolic dysfunction and might also be used to detect systolic dysfunction at rest. Furthermore, measurement of circulating levels of cardiac biomarkers could improve the diagnostic assessm+ent. Cirrhotic cardiomyopathy contributes to various complications in cirrhosis, especially as an important factor in the development of hepatic nephropathy. Additionally, cirrhotic cardiomyopathy seems to be associated with the development of heart failure in relation to invasive procedures such as shunt insertion and liver transplantation. Current pharmacological treatment is nonspecific and directed towards left ventricular failure, and liver transplantation is currently the only proven treatment with specific effect on cirrhotic cardiomyopathy. PMID- 24217348 TI - The promise and challenges of next-generation genome sequencing for clinical care. AB - With increased speed and decreased costs, next-generation gene sequencing has the potential to improve medical care by making possible widespread evaluation of patients' genomes in clinical settings. The entire genome of an individual can now be sequenced in less than 1 week at a cost of $5000 to $10,000; the cost will continue to decline. Analyses based on next-generation sequencing include whole genome sequencing and whole-exome sequencing; DNA sequences that encode proteins are collectively known as the exome. In some instances, whole genome and whole exome sequencing have already helped to accurately diagnose diseases with atypical manifestations, that are difficult to diagnose using clinical or laboratory criteria alone, or that otherwise require extensive or costly evaluation. For some patients with malignant neoplasms, next-generating sequencing can improve tumor classification, diagnosis, and management. Many challenges remain, however, such as the storage and interpretation of vast amounts of sequence data, training physicians and other health care professionals whose knowledge of genetics may be insufficient, effective genetic counseling and communication of results to patients, and establishing standards for the appropriate use of the technology. Rigorous studies are needed to assess the utility of whole-genome and whole-exome sequencing in large groups of patients, including comparative studies with other approaches to screening and diagnosis, and the evaluation of clinical end points and health care costs. The successes to date have been in single cases or in very small groups of patients. At present, although whole-genome or whole-exome sequencing show great promise, they should be incorporated into patient care only in limited clinical situations. PMID- 24217349 TI - In vivo imaging with a fundus camera in a rat model of laser-induced choroidal neovascularization. AB - PURPOSE: To investigate the use of imaging and quantitative measurement capabilities of a modified fundus camera in a rat model of laser-induced choroidal neovascularization. METHODS: Following induction of experimental choroidal neovascularization, Dark Agouti rats underwent serial in vivo imaging with a fundus camera (FF450plus, Carl Zeiss MediTec, Jena, Germany), including color, reflectance and fluorescence imaging. RESULTS: A custom-made setting allowed high-resolution imaging. Change of fluorescence intensity following intravenous or intravitreal dye injection could be quantitatively monitored over time. Hardware binning resulted in an improved signal-to-noise ratio and a reduction of flash light intensity. Simultaneous fluorescence imaging following injection of two different dendritic polygylcerol sulfate dyes could be demonstrated. CONCLUSION: This study demonstrates the use and optimizations of a fundus camera for various in vivo imaging modalities in rats. Molecular imaging of the eye may allow for better insights into cellular dysfunction and optimization of therapeutic strategies. PMID- 24217350 TI - Selective trioxolane based bifunctional molecular linkers for covalent heme surface functionalisation. AB - A bifunctional molecular linker containing both aryl diazonium and trioxolane groups was synthesised and its ability to sequentially functionalise glassy carbon and covalently immobilise heme investigated. Functionalisation was demonstrated by electrochemical techniques. PMID- 24217352 TI - Child abuse prevention and child home visitation: making sure we get it right. PMID- 24217353 TI - A multifunctional joint angle sensor with measurement adaptability. AB - The paper presents a multifunctional joint sensor with measurement adaptability for biological engineering applications, such as gait analysis, gesture recognition, etc. The adaptability is embodied in both static and dynamic environment measurements, both of body pose and in motion capture. Its multifunctional capabilities lay in its ability of simultaneous measurement of multiple degrees of freedom (MDOF) with a single sensor to reduce system complexity. The basic working mode enables 2DOF spatial angle measurement over big ranges and stands out for its applications on different joints of different individuals without recalibration. The optional advanced working mode enables an additional DOF measurement for various applications. By employing corrugated tube as the main body, the sensor is also characterized as flexible and wearable with less restraints. MDOF variations are converted to linear displacements of the sensing elements. The simple reconstruction algorithm and small outputs volume are capable of providing real-time angles and long-term monitoring. The performance assessment of the built prototype is promising enough to indicate the feasibility of the sensor. PMID- 24217354 TI - Violin bridge mobility analysis under in-plane excitation. AB - The vibration of a violin bridge is a dynamic contact vibration with two interfaces: strings-bridge, and bridge feet-top plate. In this paper, the mobility of an isolated bridge under in-plane excitation is explored using finite element modeling based on the contact vibration model. Numerical results show that the dynamic contact stiffness in the two contact interfaces has a great impact on the bridge mobility. A main resonance peak is observed in the frequency range of 2-3 kHz in the frequency response of the isolated bridge when the contact stiffness is smaller than a critical threshold. The main resonance peak frequency is affected by the contact stiffness as well. In order to verify the numerical findings, a novel experimental system is then designed on the basis of a piezoelectric dynamometer for bridge mobility analysis. Experimental results confirm the impact of the dynamic contact stiffness on the bridge mobility. PMID- 24217355 TI - A Kalman filter implementation for precision improvement in low-cost GPS positioning of tractors. AB - Low-cost GPS receivers provide geodetic positioning information using the NMEA protocol, usually with eight digits for latitude and nine digits for longitude. When these geodetic coordinates are converted into Cartesian coordinates, the positions fit in a quantization grid of some decimeters in size, the dimensions of which vary depending on the point of the terrestrial surface. The aim of this study is to reduce the quantization errors of some low-cost GPS receivers by using a Kalman filter. Kinematic tractor model equations were employed to particularize the filter, which was tuned by applying Monte Carlo techniques to eighteen straight trajectories, to select the covariance matrices that produced the lowest Root Mean Square Error in these trajectories. Filter performance was tested by using straight tractor paths, which were either simulated or real trajectories acquired by a GPS receiver. The results show that the filter can reduce the quantization error in distance by around 43%. Moreover, it reduces the standard deviation of the heading by 75%. Data suggest that the proposed filter can satisfactorily preprocess the low-cost GPS receiver data when used in an assistance guidance GPS system for tractors. It could also be useful to smooth tractor GPS trajectories that are sharpened when the tractor moves over rough terrain. PMID- 24217356 TI - Metallic and ceramic thin film thermocouples for gas turbine engines. AB - Temperatures of hot section components in today's gas turbine engines reach as high as 1,500 degrees C, making in situ monitoring of the severe temperature gradients within the engine rather difficult. Therefore, there is a need to develop instrumentation (i.e., thermocouples and strain gauges) for these turbine engines that can survive these harsh environments. Refractory metal and ceramic thin film thermocouples are well suited for this task since they have excellent chemical and electrical stability at high temperatures in oxidizing atmospheres, they are compatible with thermal barrier coatings commonly employed in today's engines, they have greater sensitivity than conventional wire thermocouples, and they are non-invasive to combustion aerodynamics in the engine. Thin film thermocouples based on platinum:palladium and indium oxynitride:indium tin oxynitride as well as their oxide counterparts have been developed for this purpose and have proven to be more stable than conventional type-S and type-K thin film thermocouples. The metallic and ceramic thin film thermocouples described within this paper exhibited remarkable stability and drift rates similar to bulk (wire) thermocouples. PMID- 24217357 TI - Label-enhanced surface plasmon resonance: a new concept for improved performance in optical biosensor analysis. AB - Surface plasmon resonance (SPR) is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations. PMID- 24217358 TI - Improving management performance of P2PSIP for mobile sensing in wireless overlays. AB - Future wireless communications are heading towards an all-Internet Protocol (all IP) design, and will rely on the Session Initiation Protocol (SIP) to manage services, such as voice over IP (VoIP). The centralized architecture of traditional SIP has numerous disadvantages for mobile ad hoc services that may be possibly overcome by advanced peer-to-peer (P2P) technologies initially developed for the Internet. In the context of mobile sensing, P2PSIP protocols facilitate decentralized and fast communications with sensor-enabled terminals. Nevertheless, in order to make P2PSIP protocols feasible in mobile sensing networks, it is necessary to minimize overhead transmissions for signaling purposes, which reduces the battery lifetime. In this paper, we present a solution to improve the management of wireless overlay networks by defining an adaptive algorithm for the calculation of refresh time. The main advantage of the proposed algorithm is that it takes into account new parameters, such as the delay between nodes, and provides satisfactory performance and reliability levels at a much lower management overhead than previous approaches. The proposed solution can be applied to many structured P2P overlays or P2PSIP protocols. We evaluate it with Kademlia-based distributed hash tables (DHT) and dSIP. PMID- 24217359 TI - Throughput and energy efficiency of a cooperative hybrid ARQ protocol for underwater acoustic sensor networks. AB - Due to its efficiency, reliability and better channel and resource utilization, cooperative transmission technologies have been attractive options in underwater as well as terrestrial sensor networks. Their performance can be further improved if merged with forward error correction (FEC) techniques. In this paper, we propose and analyze a retransmission protocol named Cooperative-Hybrid Automatic Repeat reQuest (C-HARQ) for underwater acoustic sensor networks, which exploits both the reliability of cooperative ARQ (CARQ) and the efficiency of incremental redundancy-hybrid ARQ (IR-HARQ) using rate-compatible punctured convolution (RCPC) codes. Extensive Monte Carlo simulations are performed to investigate the performance of the protocol, in terms of both throughput and energy efficiency. The results clearly reveal the enhancement in performance achieved by the C-HARQ protocol, which outperforms both CARQ and conventional stop and wait ARQ (S&W ARQ). Further, using computer simulations, optimum values of various network parameters are estimated so as to extract the best performance out of the C-HARQ protocol. PMID- 24217360 TI - Research on the design of an optical information storage sensing system using a diffractive optical element. AB - This paper introduces a compact optical information storage sensing system. Applications of this system include longitudinal surface plasmon resonance detection of gold nanorods with a single femtosecond laser in three-dimensional space as well as data storage. A diffractive optical element (DOE) is applied in the system to separate the recording-reading beam from the servo beam. This allows us to apply a single laser and one objective lens in a single optical path for the servo beam and the recording-reading beam. The optical system has a linear region of 8 lambda, which is compatible with current DVD servo modules. The wavefront error of the optical system is below 0.03 lambda(rms). The minimum grating period of the DOE is 13.4 um, and the depth of the DOE is 1.2 um, which makes fabrication of it possible. The DOE is also designed to conveniently control the layer-selection process, as there is a linear correlation between the displacement of the DOE and the layer-selection distance. The displacement of DOE is in the range of 0-6.045 mm when the thickness of the layer-selection is 0.3 mm. Experiments were performed and the results have been verified. PMID- 24217361 TI - Analysis of the purpose of state health departments' tweets: information sharing, engagement, and action. AB - BACKGROUND: Public health agencies are actively using social media, including Twitter. In the public health and nonprofit sectors, Twitter has been limited to one-way communication. Two-way, interactive communication on Twitter has the potential to enhance organizational relationships with followers and help organizations achieve their goals by increasing communication and dialog between the organization and its followers. Research shows that nonprofit organizations use Twitter for three main functions: information sharing, community building, and action. OBJECTIVE: It is not known whether state health departments are using Twitter primarily for one-way information sharing or if they are trying to engage followers to build relationships and promote action. The purpose of this research was to discover what the primary function of Twitter use is among state health departments in the United States and whether this is similar to or different from nonprofit organizations. METHODS: A complete list of "tweets" made by each state health department account was obtained using the Twitter application programming interface. We randomly sampled 10% of each state health department's tweets. Four research assistants hand-coded the tweets' primary focus (organization centric or personal health information centric) and then the subcategories of information dissemination, engagement, or action. Research assistants coded each tweet for interactivity, sophistication, and redirects to another website. Data were analyzed using SPSS version 20. RESULTS: There were 4221 tweets from 39 state health departments. There was no statistically significant difference in the number of tweets made by a state health department and the state population density (P=.25). The majority of tweets focused on personal health topics (69.37%, 2928/4221) while one-third were tweets about the organization (29.14% , 1230/4221). The main function of organization-based tweets was engagement through conversations to build community (65.77%, 809/1236). These engagement-related tweets were primarily recognition of other organizations' events (43.6%, 353/809) and giving thanks and recognition (21.4%, 173/809). Nearly all of the personal health information-centric tweets involved general public health information (92.10%, 1399/1519) and 79.03% (3336/4221) of tweets directed followers to another link for more information. CONCLUSIONS: This is the first study to assess the purpose of public health tweets among state health departments. State health departments are using Twitter as a one-way communication tool, with tweets focused primarily on personal health. A state health department Twitter account may not be the primary health information source for individuals. Therefore, state health departments should reconsider their focus on personal health tweets and envision how they can use Twitter to develop relationships with community agencies and partners. In order to realize the potential of Twitter to establish relationships and develop connections, more two-way communication and interaction are essential. PMID- 24217362 TI - Noninvasive brain stimulation for treatment of right- and left-handed poststroke aphasics. AB - BACKGROUND: Accumulating evidence from single case studies, small case series and randomized controlled trials seems to suggest that inhibitory noninvasive brain stimulation (NIBS) over the contralesional inferior frontal gyrus (IFG) of right handers in conjunction with speech and language therapy (SLT) improves recovery from poststroke aphasia. Application of inhibitory NIBS to improve recovery in left-handed patients has not yet been reported. METHODS: A total of 29 right handed subacute poststroke aphasics were randomized to receive either 10 sessions of SLT following 20 min of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the contralesional IFG or 10 sessions of SLT following sham stimulation; 2 left-handers were treated according to the same protocol with real rTMS. Language activation patterns were assessed with positron emission tomography prior to and after the treatment; 95% confidence intervals for changes in language performance scores and the activated brain volumes in both hemispheres were derived from TMS- and sham-treated right-handed patients and compared to the same parameters in left-handers. RESULTS: Right-handed patients treated with rTMS showed better recovery of language function in global aphasia test scores (t test, p < 0.002) as well as in picture-naming performance (ANOVA, p = 0.03) than sham-treated right-handers. In treated right-handers, a shift of activation to the ipsilesional hemisphere was observed, while sham-treated patients consolidated network activity in the contralesional hemisphere (repeated measures ANOVA, p = 0.009). Both left-handed patients also improved, with 1 patient within the confidence limits of TMS-treated right-handers (23 points, 15.9-28.9) and the other patient within the limits of sham-treated subjects (8 points, 2.8-14.5). Both patients exhibited only a very small interhemispheric shift, much less than expected in TMS-treated right-handers, and more or less consolidated initially active networks in both hemispheres. CONCLUSION: Inhibitory rTMS over the nondominant IFG appears to be a safe and effective treatment for right-handed poststroke aphasics. In the 2 cases of left-handed aphasics no deterioration of language performance was observed with this protocol. However, therapeutic efficiency is less obvious and seems to be more related to the dominance pattern prior to the stroke than to the TMS intervention. PMID- 24217363 TI - Sodium and potassium competition in potassium-selective and non-selective channels. AB - Potassium channels selectively conduct K(+), primarily to the exclusion of Na(+), despite the fact that both ions can bind within the selectivity filter. Here we perform crystallographic titration and single-channel electrophysiology to examine the competition of Na(+) and K(+) binding within the filter of two NaK channel mutants; one is the potassium-selective NaK2K mutant and the other is the non-selective NaK2CNG, a CNG channel pore mimic. With high-resolution structures of these engineered NaK channel constructs, we explicitly describe the changes in K(+) occupancy within the filter upon Na(+) competition by anomalous diffraction. Our results demonstrate that the non-selective NaK2CNG still retains a K(+) selective site at equilibrium, whereas the NaK2K channel filter maintains two high-affinity K(+) sites. A double-barrier mechanism is proposed to explain K(+) channel selectivity at low K(+) concentrations. PMID- 24217366 TI - Recognition of most outstanding resident publication. PMID- 24217364 TI - Analysis of germline gene copy number variants of patients with sporadic pancreatic adenocarcinoma reveals specific variations. AB - OBJECTIVES: The rapid fatality of pancreatic cancer is, in large part, the result of diagnosis at an advanced stage in the majority of patients. Identification of individuals at risk of developing pancreatic adenocarcinoma would be useful to improve the prognosis of this disease. There is presently no biological or genetic indicator allowing the detection of patients at risk. Our main goal was to identify copy number variants (CNVs) common to all patients with sporadic pancreatic cancer. METHODS: We analyzed gene CNVs in leukocyte DNA from 31 patients with sporadic pancreatic adenocarcinoma and from 93 matched controls. Genotyping was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). RESULTS: We identified 431 single nucleotide polymorphism (SNP) probes with abnormal hybridization signal present in the DNA of all 31 patients. Of these SNP probes, 284 corresponded to 3 or more copies and 147 corresponded to 1 or 0 copies. Several cancer-associated genes were amplified in all patients. Conversely, several genes supposed to oppose cancer development were present as single copy. CONCLUSIONS: These data suggest that a set of 431 CNVs could be associated with the disease. This set could be useful for early diagnosis. PMID- 24217367 TI - Out-sourcing stem cells for clinical applications. PMID- 24217368 TI - Validation of a conical cuff on the forearm for estimating radial artery blood pressure. AB - INTRODUCTION: There has been a growing need for and interest in measuring noninvasive blood pressure (NIBP) in obese patients. In many situations, available rectangular upper arm blood pressure cuffs do not fit properly, closing in a crisscross manner or overlapping the elbow. To address this issue, GE Healthcare has designed a conically shaped cuff for use on the forearm to estimate radial arterial blood pressure. This study evaluated using this forearm cuff with an oscillometric NIBP algorithm compared with an invasive radial arterial blood pressure reference. PATIENTS AND METHODS: Thirty-four patients were enrolled in the study with an aim to acquire a minimum of 150 paired measurements. Blood pressure was measured and recorded invasively from the radial artery of each patient, while noninvasive oscillometric measurements were acquired from the same limb using a conically shaped cuff placed on the patient's forearm. ANALYSIS: NIBP values were compared with the invasive blood pressure values acquired in the combined 30-s period preceding cuff inflation and the 30-s period following cuff deflation. The acceptance criteria for measurement accuracy were defined in accordance with the ANSI/AAMI/ISO 81060-2:2009 standard, which requires an absolute average error of 5 mmHg or less, with an SD of 8 mmHg or less. RESULTS: The systolic mean error (-0.82 mmHg) and SD (6.08 mmHg) and the diastolic mean error (1.53 mmHg) and SD (3.83 mmHg) were within the 81060-2 acceptance criteria. CONCLUSION: The statistical results show that oscillometric NIBP measurements taken with the conically shaped cuff placed on the forearm give an accurate estimation of radial arterial blood pressure. PMID- 24217369 TI - Liver resection in patients with hepatic hereditary hemorrhagic telangiectasia. AB - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler Rendu-Weber disease, is a rare genetic disorder characterized by widespread telangiectasia and vascular malformations involving the liver in most of the cases. The consequences of this pathologically underlying parenchyma on liver resection have been poorly described. METHODS: More than 2,000 liver resections were performed at our institution over a 14-year period, whereby 2 major hepatectomies for malignancy were performed on patients with HHT with liver involvement. In addition, a systematic search was performed in the PubMed database to identify all original articles on hepatectomy in patients with HHT. RESULTS: The first patient underwent a left hepatectomy for cholangiocarcinoma with an uneventful postoperative course. The second patient underwent right hepatectomy and segment 3 resection for colorectal liver metastases. The postoperative course was marked by ascites without liver failure. For both patients, 90-day mortality was nil. CONCLUSION: In selected HHT patients with liver involvement, liver resections, including major hepatectomies, can be safely performed. Specific attention should be paid to postoperative liver function and ascites. PMID- 24217370 TI - Construction of heterocyclic structures by trivalent cerium salts promoted bond forming reactions. AB - Cerium(III) salts have recently gained increasing attention in the synthetic community, owing to the powerful features that are reviewed in detail in this tutorial. This review reports significant examples of cerium(III) promoted synthesis of heterocyclic structures, initially dealing with the synthesis of five- and six-membered ring nitrogen containing heterocycles, then describing the preparation of their oxygenated analogues and finally discussing the achievement of seven-membered rings and mixed heterocyclic motifs. PMID- 24217371 TI - B1 was the ancestor B chromosome variant in the western Mediterranean area in the grasshopper Eyprepocnemis plorans. AB - We analyzed the distribution of 2 repetitive DNAs, i.e. ribosomal DNA (rDNA) and a satellite DNA (satDNA), on the B chromosomes found in 17 natural populations of the grasshopper Eyprepocnemis ploransplorans sampled around the western Mediterranean region, including the Iberian Peninsula, Balearic Islands, Sicily, and Tunisia. Based on the amount of these repetitive DNAs, 4 types of B variants were found: B1, showing an equal or higher amount of rDNA than satDNA, and 3 other variants, B2, B24 and B5, bearing a higher amount of satDNA than rDNA. The variants B1 and B2 varied in size among populations: B1 was about half the size of the X chromosome in Balearic Islands, but two-thirds of the X in Iberian populations at Alicante, Murcia and Albacete provinces. Likewise, B2 was about one-third the size of the X chromosome in populations from the Granada province but half the size of the X in the populations collected at Malaga province. The widespread geographical distribution of the B1 variant makes it the best candidate for being the ancestor B chromosome in the whole western Mediterranean region. PMID- 24217372 TI - Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction. AB - OBJECTIVE: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. PATIENTS AND METHODS: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). RESULTS: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. CONCLUSIONS: UA Doppler discriminated better the two forms of FGR with average early- and late onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR. PMID- 24217373 TI - Cryptic speciation or global spread? The case of a cosmopolitan marine invertebrate with limited dispersal capabilities. AB - The existence of globally-distributed species with low dispersal capabilities is a paradox that has been explained as a result of human-mediated transport and by hidden diversity in the form of unrecognized cryptic species. Both factors are not mutually exclusive, but relatively few studies have demonstrated the presence of both. Here we analyse the genetic patterns of the colonial ascidian Diplosoma listerianum, a species nowadays distributed globally. The study of a fragment of a mitochondrial gene in localities worldwide revealed the existence of multiple cryptic species. In addition, we found a complex geographic structure and multiple clades occurred in sympatry. One of the species showed strong population structure irrespective of geographical distances, which is coherent with stochastic dispersal linked to human transport. The present study shows the complexity of discerning the role of cryptic diversity from human-driven range shifts worldwide, as well as disentangling the effects of natural and artificial dispersal. PMID- 24217377 TI - Origins of diagnostic error. PMID- 24217378 TI - Origins of diagnostic error--reply. PMID- 24217379 TI - Administrative overload as a cause of diagnostic error. PMID- 24217380 TI - Cardiac symptoms in women and men. PMID- 24217381 TI - Administrative overload as a cause of diagnostic error--reply. PMID- 24217382 TI - Cardiac symptoms in women and men. PMID- 24217383 TI - Cardiac symptoms in women and men. PMID- 24217384 TI - Cardiac symptoms in women and men--reply. PMID- 24217385 TI - Understanding drug effects in older people: the role of pharmacology. PMID- 24217386 TI - Understanding drug effects in older people: the role of pharmacology--reply. PMID- 24217387 TI - Synthesis and internal electric field dependent photoreactivity of Bi3O4Cl single crystalline nanosheets with high {001} facet exposure percentages. AB - We prepared Bi3O4Cl single-crystalline nanosheets with high {001} facet exposure percentages and demonstrated that their photoreactivity strongly depended on the magnitude of the internal electric field (IEF), which was correlated with the {001} facet exposure percentage. More {001} facet exposure could induce the generation of stronger IEF, which favored the photogenerated charge separation and transfer, and thus enhancing the photoreactivity. PMID- 24217388 TI - Gain of 20q11.21 in human embryonic stem cells improves cell survival by increased expression of Bcl-xL. AB - Gain of 20q11.21 is a chromosomal abnormality that is recurrently found in human pluripotent stem cells and cancers, strongly suggesting that this mutation confers a proliferative or survival advantage to these cells. In this work we studied three human embryonic stem cell (hESC) lines that acquired a gain of 20q11.21 during in vitro culture. The study of the mRNA gene expression levels of the loci located in the common region of duplication showed that HM13, ID1, BCL2L1, KIF3B and the immature form of the micro-RNA miR-1825 were up-regulated in mutant cells. ID1 and BCL2L1 were further studied as potential drivers of the phenotype of hESC with a 20q11.21 gain. We found no increase in the protein levels of ID1, nor the downstream effects expected from over-expression of this gene. On the other hand, hESC with a gain of 20q11.21 had on average a 3-fold increase of Bcl-xL (the anti-apoptotic isoform of BCL2L1) protein levels. The mutant hESC underwent 2- to 3-fold less apoptosis upon loss of cell-to-cell contact and were ~2-fold more efficient in forming colonies from a single cell. The key role of BCL2L1 in this mutation was further confirmed by transgenic over expression of BCL2L1 in the wild-type cells, leading to apoptosis-resistant cells, and BCL2L1-knock-down in the mutant hESC, resulting in a restoration of the wild-type phenotype. This resistance to apoptosis supposes a significant advantage for the mutant cells, explaining the high frequency of gains of 20q11.21 in human pluripotent stem cells. PMID- 24217389 TI - Species-specific differences in follicular antral sizes result from diffusion based limitations on the thickness of the granulosa cell layer. AB - The size of mature oocytes is similar across mammalian species, yet the size of ovarian follicles increases with species size, with some ovarian follicles reaching diameters>1000-fold the size of the enclosed oocyte. Here we show that the different follicular sizes can be explained with diffusion-based limitations on the thickness of the hormone-secreting granulosa layer. By analysing published data on human follicular growth and granulosa cell expansion during follicular maturation we find that the 4-fold increase of the antral follicle diameter is entirely driven by an increase in the follicular fluid volume, while the thickness of the surrounding granulosa layer remains constant at ~45+/-10 um. Based on the measured kinetic constants, the model reveals that the observed fall in the gonadotrophin concentration from peripheral blood circulation to the follicular antrum is a result of sequestration in the granulosa. The model further shows that as a result of sequestration, an increased granulosa thickness cannot substantially increase estradiol production but rather deprives the oocyte from gonadotrophins. Larger animals (with a larger blood volume) require more estradiol as produced by the ovaries to down-regulate follicle-stimulating hormone-secretion in the pituitary. Larger follicle diameters result in larger follicle surface areas for constant granulosa layer thickness. The reported increase in the follicular surface area in larger species indeed correlates linearly both with species mass and with the predicted increase in estradiol output. In summary, we propose a structural role for the antrum in that it determines the volume of the granulosa layer and thus the level of estrogen production. PMID- 24217390 TI - Pleural effusions, eosinophilia and a positive interferon-gamma release assay. PMID- 24217391 TI - Institute of medicine report: new directions in child abuse and neglect research. PMID- 24217393 TI - Recalibration of subjective simultaneity between self-generated movement and delayed auditory feedback. AB - Temporal contingency between motor commands and corresponding auditory feedback is crucial for perception of self-generated sound as well as external auditory events. The present study examined whether delay detection of self-generated sound was affected by the range of delayed auditory feedback used during the experiment. Participants pressed a button with their right index finger and judged whether auditory feedback was delayed compared with the sensation of finger movement. The range of auditory feedback delay was varied across conditions. To calculate the delay detection threshold (DDT), that is, the point at which the delay detection rate was 50%, we fitted a logistic function to the delay-detection probability curve. The DDT was significantly different across conditions (Tukey-Kramer's honestly significant difference test, P<0.01). Specifically, the DDT became longer as the mean delay of the range increased. However, this shift was not observed for the delay range with a minimum delay greater than 250 ms. We propose that the subjective simultaneity of auditory feedback and self-body movement is, to some extent, automatically recalibrated toward the mean delay of the delay range used in the experiment. PMID- 24217394 TI - Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase. AB - SAMHD1 is a dGTP-activated deoxynucleoside triphosphate triphosphohydrolase (dNTPase) whose dNTPase activity has been linked to HIV/SIV restriction. The mechanism of its dGTP-activated dNTPase function remains unclear. Recent data also indicate that SAMHD1 regulates retrotransposition of LINE-1 elements. Here we report the 1.8-A crystal structure of homotetrameric SAMHD1 in complex with the allosteric activator and substrate dGTP/dATP. The structure indicates the mechanism of dGTP-dependent tetramer formation, which requires the cooperation of three subunits and two dGTP/dATP molecules at each allosteric site. Allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced SAMHD1 dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated LINE-1 regulation. The structural and functional information provided here should facilitate future investigation of SAMHD1 function, including dNTPase activity, LINE-1 modulation and HIV-1 restriction. PMID- 24217395 TI - Is atrial fibrillation always a culprit of stroke in patients with atrial fibrillation plus stroke? AB - BACKGROUND: Some ischemic strokes in patients with atrial fibrillation (AF) are caused by noncardioembolic etiologies (AF-unrelated stroke), but not AF itself (AF-related stroke). However, most clinical trials on the risk of stroke in AF have not distinguished between these. We investigated the frequency and features of AF-unrelated versus AF-related strokes in patients with AF plus ischemic stroke. We hypothesized that certain clinical factors, including chronicity of AF, treatment at the time of stroke onset and echocardiographic findings, may help to discriminate between AF-related and AF-unrelated strokes. The mechanisms and antithrombotic medications at the time of stroke recurrence in the two groups were also examined. METHODS: Consecutive patients with ischemic stroke within 7 days of symptom onset and with AF were included. Patients were classified according to the previously published criteria. Clinical factors including CHADS2 and CHA2DS2-VASc scores and transthoracic echocardiographic (TTE) findings were evaluated. RESULTS: Of 522 patients, 424 (81.2%) were grouped as AF-related stroke and the remaining 90 (17.2%) were classified as AF-unrelated stroke. Among the patients with AF-unrelated stroke, 51 (9.8%) were categorized as possible large artery atherosclerosis and 38 (7.3%) as possible small artery occlusion; 1 patient (0.2%) was assigned to miscellaneous cause. The AF-related and AF unrelated strokes had similar CHADS2 and CHA2DS2-VASc scores. However, compared to AF-unrelated stroke, AF-related stroke was independently associated with female sex (odds ratio, OR, 2.19; 95% confidence interval, CI, 1.18-4.05), sustained AF (OR, 2.09; 95% CI, 1.21-3.59), inadequate anticoagulation at stroke onset (OR, 3.21; 95% CI, 1.33-7.75) and left ventricular dysfunction on TTE (OR, 2.84; 95% CI, 1.40-5.74). We identified 26 patients who experienced 2 strokes during the study period. The initial stroke subtype was a strong predictor of the recurrent stroke mechanism (p < 0.001). Among 17 events of AF-related recurrent stroke in these subpopulation, only 2 strokes (11.8%) occurred in a setting of adequate anticoagulation, whereas 4 out of 9 patients (44.4%) who had AF unrelated strokes at recurrence were sufficiently anticoagulated at the time of admission (p = 0.138). CONCLUSION: AF is not always a culprit of stroke in patients with AF plus ischemic stroke; approximately one sixth of these cases are unrelated to AF and have distinct characteristics compared to AF-related stroke. There are significant differences in terms of some clinical and TTE parameters between AF-related and AF-unrelated stroke. Future studies are warranted to optimize strategies for risk stratification, treatment and prevention of stroke in these patients. PMID- 24217396 TI - Association between free light chain levels, and disease progression and mortality in chronic kidney disease. AB - Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa (kappa) and lambda (lambda) and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain kappa and lambda levels were found to be elevated in CKD patients (especially in those on hemodialysis). Furthermore, FLC kappa and lambda levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC kappa and lambda levels were independently associated with CKD stages and beta2 microglobulin levels. Elevated FLC kappa and lambda levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC kappa and lambda levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors. PMID- 24217397 TI - Shiga toxin type 2dact displays increased binding to globotriaosylceramide in vitro and increased lethality in mice after activation by elastase. AB - Shiga toxin type 2dact (Stx2dact), an Stx2 variant originally identified from Escherichia coli O91:H21 strain B2F1, displays increased cytotoxicity after activation by elastase present in intestinal mucus. Activation is a result of cleavage of two amino acids from the C-terminal tail of the A2 subunit. In this study, we hypothesized that activation leads to increased binding of toxin to its receptor on host cells both in vitro and in vivo. To test this theory, Stx2dact was treated with elastase or buffer alone and then each toxin was assessed for binding to purified globotriaosylceramide (Gb3) in an enzyme-linked immunosorbent assay, or cells in culture by immunofluorescence, or flow cytometry. Elastase- and buffer-treated Stx2dact were also evaluated for binding to mouse kidney tissue and for relative lethality in mice. We found that activated Stx2dact had a greater capacity to bind purified Gb3, cells in culture, and mouse kidney tissue and was more toxic for mice than was non-activated Stx2dact. Thus, one possible mechanism for the augmented cytotoxicity of Stx2dact after activation is its increased capacity to bind target cells, which, in turn, may cause greater lethality of elastase-treated toxin for mice and enhanced virulence for humans of E. coli strains that express Stx2dact. PMID- 24217398 TI - Oral toxicity of okadaic acid in mice: study of lethality, organ damage, distribution and effects on detoxifying gene expression. AB - In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals. PMID- 24217399 TI - Heterogeneous photocatalytic nanomaterials: prospects and challenges in selective transformations of biomass-derived compounds. AB - Heterogeneous photocatalysis has become a comprehensively studied area of research during the past three decades due to its practical interest in applications including water-air depollution, cancer therapy, sterilization, artificial photosynthesis (CO2 photoreduction), anti-fogging surfaces, heat transfer and heat dissipation, anticorrosion, lithography, photochromism, solar chemicals production and many others. The utilization of solar irradiation to supply energy or to initiate chemical reactions is already an established idea. Excited electron-hole pairs are generated upon light irradiation of a wide-band gap semiconductor which can be applied to solar cells to generate electricity or in chemical processes to create/degrade specific compounds. While the field of heterogeneous photocatalysis for pollutant abatement and mineralisation of contaminants has been extensively investigated, a new research avenue related to the selective valorisation of residues has recently emerged as a promising alternative to utilise solar light for the production of valuable chemicals and fuels. This tutorial review will focus on the potential and applications of solid photonanocatalysts for the selective transformation of biomass-derived substrates. PMID- 24217400 TI - The germline BIM deletion polymorphism is not associated with the treatment efficacy of sorafenib in patients with advanced hepatocellular carcinoma. AB - OBJECTIVES: A germline BIM deletion polymorphism has been proposed to predict a poor treatment efficacy of certain kinase inhibitors. The current study aimed to explore whether the BIM deletion polymorphism predicts the treatment efficacy of sorafenib for advanced hepatocellular carcinoma (HCC). METHODS: All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to providing peripheral blood samples were included. Polymerase chain reaction followed by gel electrophoresis was used to detect the germline BIM deletion polymorphism. RESULTS: A total of 89 patients were enrolled; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. The heterozygous BIM deletion polymorphism was identified in 9 (10%) patients. Patients with and without the BIM deletion polymorphism had similar response rates (11 vs. 6%) and disease control rates (56 vs. 61%). The time to progression, progression-free survival, and overall survival were similar between patients with and without the BIM deletion polymorphism. After adjusting for basic clinicopathologic variables and treatment regimens, the BIM polymorphism still could not predict treatment outcomes. CONCLUSIONS: The BIM deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC. PMID- 24217401 TI - Relationship between obstructive sleep apnea and coronary microcirculatory function among patients with cardiac syndrome X. AB - OBJECTIVES: Obstructive sleep apnea (OSA) is an emerging risk factor for cardiovascular disease. Microcirculatory dysfunction has been proposed as a potential mechanism in the pathogenesis of cardiovascular disease in OSA. This study aims to investigate the relationship between OSA and coronary microcirculatory function. PATIENTS AND METHODS: One thousand and thirty-eight patients (598 female, mean age 60+/-9 years) with angiographically normal coronary arteries were divided into three groups with non-OSA of apnea-hypopnea index (AHI) less than 5 (n=403), mild-to-moderate OSA of AHI 5-30 (n=386), and severe OSA of AHI more than 30 (n=249). RESULTS: The prevalence of OSA was very high in patients with syndrome X (635/1038). Patients with higher AHI values had a lower coronary flow reserve, were more likely to have a higher total cholesterol, low-density lipoprotein cholesterol, and high sensitive C-reactive protein, and were more likely to be obese. Compared with the non-OSA group, the multivariable-adjusted odds ratio of coronary microcirculatory function for an AHI of 5-30 events/h was 1.93, 95% confidence interval 1.66-3.47, P=0.038, and for an AHI of more than 30 events/h was 2.18, 95% confidence interval 1.62-4.23, P=0.024, in model 1; and coronary microcirculatory function for an AHI of 5-30 events/h and more than 30 events/h odds ratio 1.31, 95% confidence interval 1.06 2.88, P=0.043, versus odds ratio 2.08, 95% confidence interval 1.03-2.16, P=0.036, in model 2. CONCLUSION: As compared with having no sleep apnea, categories with higher AHI were associated with increased odds of lower coronary flow reserve. The data suggested a close relationship between OSA and coronary microcirculatory function in atherosclerosis. PMID- 24217402 TI - Relation between N-terminal pro-brain natriuretic peptide levels and response to enhanced external counterpulsation in chronic angina pectoris. AB - OBJECTIVE: Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response. METHODS: We explored a database of n=53 patients who had undergone clinically indicated EECP during 35 1 h sessions in our unit (65+/-7 years; 49 male), and sought to clarify which factors are predictive of response. Efficiency of counterpulsation was measured as the diastolic augmentation (DA) ratio, and was recorded both at beginning and end of the EECP treatment course. An increase in 6-min walk (6MW) distance of 5% was indicative of clinical response. RESULTS: Response occurred in 28 patients (53%; nonresponse in n=25, 47%). Responders had shorter baseline 6MW distance (377+/-81 vs. 445+/-62 m; P<0.01), lower left ventricular ejection fraction (48+/ 9 vs. 54+/-8%; P<0.05), frequently had an increase in DA ratio during the EECP treatment course (23/28 vs. 5/28 with unchanged or decreased DA ratio; P<0.05), and higher levels of N-terminal pro-brain natriuretic peptide [NT-proBNP; 256 (123-547) vs. 62 (26-444) ng/l, P<0.01]. In multivariate logistic regression, response was independently predicted by baseline 6MW distance and baseline NT proBNP levels (P<0.05 for both; model sensitivity: 82%, specificity: 72%, accuracy: 79%). CONCLUSION: There is larger clinical benefit of EECP in patients with greater functional impairment and higher levels of NT-proBNP. PMID- 24217403 TI - Prevalence of ischemia on myocardial perfusion scintigraphy of pre-and postmenopausal women. AB - BACKGROUND: In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established. OBJECTIVES: To compare the prevalence of ischemia on Tc99m sestamibi myocardial perfusion scintigraphy (MPS) in pre- and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD. METHODS: This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value < 0.05 being considered significant. RESULTS: Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = < 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004). CONCLUSION: The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause. PMID- 24217404 TI - A new tissue Doppler index to predict cardiac death in patients with heart failure. AB - BACKGROUND: It has been shown that a new tissue Doppler index, E/(E'*S'), including the ratio between early diastolic transmitral and mitral annular velocity (E/E'), and the systolic mitral annular velocity (S'), has a good accuracy to predict left ventricular filling pressure. OBJECTIVES: We investigated the value of E/(E'*S') to predict cardiac death in patients with heart failure. METHODS: Echocardiography was performed in 339 consecutive hospitalized patients with heart failure, in sinus rhythm, after appropriate medical treatment, at discharge and after one month. Worsening of E/(E'*S') was defined as any increase of baseline value. The end point was cardiac death. RESULTS: During the follow-up period (35.2 +/- 8.8 months), cardiac death occurred in 51 patients (15%). The optimal cut-off value for the initial E/(E'*S') to predict cardiac death was 2.83 (76% sensitivity, 85% specificity). At discharge, 252 patients (74.3%) presented E/(E'*S') <= 2.83 (group I) and 87 (25.7%) presented E/(E'*S') > 2.83 (group II), respectively. Cardiac death was significantly higher in group II than in group I (38 deaths, 43.7% vs 13 deaths, 5.15%, p < 0.001). By multivariate Cox regression analysis, including variables that affected outcome in univariate analysis, E/(E'*S') at discharge was the best independent predictor of cardiac death (hazard ratio = 3.09, 95% confidence interval = 1.81-5.31, p = 0.001). Patients with E/(E'*S') > 2.83 at discharge and its worsening after one month presented the worst prognosis (all p < 0.05). CONCLUSIONS: In patients with heart failure, the E/(E'*S') ratio is a powerful predictor of cardiac death, particularly if it is associated with its worsening. PMID- 24217405 TI - The bleeding risk score as a mortality predictor in patients with acute coronary syndrome. AB - BACKGROUND: It is well known that the occurrence of bleeding increases in hospital mortality in patients with acute coronary syndromes (ACS), and there is a good correlation between bleeding risk scores and bleeding incidence. However, the role of bleeding risk score as mortality predictor is poorly studied. OBJECTIVE: The main purpose of this paper was to analyze the role of bleeding risk score as in-hospital mortality predictor in a cohort of patients with ACS treated in a single cardiology tertiary center. METHODS: Out of 1655 patients with ACS (547 with ST-elevation ACS and 1118 with non-ST-elevation ACS), we calculated the ACUITY/HORIZONS bleeding score prospectively in 249 patients and retrospectively in the remaining 1416. Mortality information and hemorrhagic complications were also obtained. RESULTS: Among the mean age of 64.3 +/- 12.6 years, the mean bleeding score was 18 +/- 7.7. The correlation between bleeding and mortality was highly significant (p < 0.001, OR = 5.296), as well as the correlation between bleeding score and in-hospital bleeding (p < 0.001, OR = 1.058), and between bleeding score and in-hospital mortality (adjusted OR = 1.121, p < 0.001, area under the ROC curve 0.753, p < 0.001). The adjusted OR and area under the ROC curve for the population with ST-elevation ACS were, respectively, 1.046 (p = 0.046) and 0.686 +/- 0.040 (p < 0.001); for non-ST elevation ACS the figures were, respectively, 1.150 (p < 0.001) and 0.769 +/- 0.036 (p < 0.001). CONCLUSIONS: Bleeding risk score is a very useful and highly reliable predictor of in-hospital mortality in a wide range of patients with acute coronary syndromes, especially in those with unstable angina or non-ST elevation acute myocardial infarction. PMID- 24217406 TI - Universal statistics of the knockout tournament. AB - We study statistics of the knockout tournament, where only the winner of a fixture progresses to the next. We assign a real number called competitiveness to each contestant and find that the resulting distribution of prize money follows a power law with an exponent close to unity if the competitiveness is a stable quantity and a decisive factor to win a match. Otherwise, the distribution is found narrow. The existing observation of power law distributions in various kinds of real sports tournaments therefore suggests that the rules of those games are constructed in such a way that it is possible to understand the games in terms of the contestants' inherent characteristics of competitiveness. PMID- 24217407 TI - Cardiac issues of noncardiac drugs: the rising story of avastin in age-related macular degeneration. AB - Emerging safety data, accompanied with recent demographic trends, point to the need for an in-depth review and consideration of potential consequences that might arise from continuing use of bevacizumab (Avastin(r)) to treat elderly patients presenting with wet age-related macular degeneration (AMD). Although it is expected that lower doses of Avastin used for intravitreal administration and an intact blood-retina barrier would reduce the systemic exposure of the drug, both animal and human studies suggest that this may not be the case. In addition, emerging real-world and clinical trial data continue to point toward compromises in both cardio- and cerebrovascular safety with Avastin. Thus, clinicians are urged to adopt the highest possible standard of care in the treatment of an already fragile AMD population. Furthermore, postmarketing surveillance and pharmacovigilance with intravitreal anti-VEGF inhibitors should remain a priority. PMID- 24217408 TI - A protecting group approach toward synthesis of Au-silica Janus nanostars. AB - The concept of protecting groups, widely used in organic chemistry, has been applied for the synthesis of Au-silica Janus stars, in which gold branches protrude from one half of Au-silica Janus spheres. This configuration opens up new possibilities to apply the plasmonic properties of gold nanostars, as well as a variety of chemical functionalizations on the silica component. PMID- 24217409 TI - Synthesis of new bioorganometallic Ir- and Rh-complexes having beta-lactam containing ligands. AB - The synthesis (and full spectroscopic and crystallographic characterization) of new classes of bioorganometallic Ir- and Rh-complexes having beta-lactam containing ligands has been achieved in three steps starting from simple precursors. The procedure for preparing these bioorganometallic compounds uses beta-lactams having a phenylpyridyl moiety attached to the C4, N1 or C4 and N1 positions simultaneously, and a directed C-H metal-insertion, in the presence of (MCp*Cl2)2 (M = Ir, Rh). Enantiomerically pure 2-azetidinones can be transformed into diastereomeric (at the metal) mixtures of enantiopure metalla-2 azetidinones. Bimetallic 2-azetidinones are also accessible by this approach. The insertion of electron-poor alkynes into the M-C bond of the bioorganometallic complex occurs regioselectively and in excellent yields. Overall, the sequence imine-beta-lactam-metalla-beta-lactam is a versatile and efficient full methodology to prepare and functionalize unprecedented, novel Ir- and Rh complexes having beta-lactam containing ligands. PMID- 24217411 TI - Bacterial physiology: vibrio uptake apparatus. PMID- 24217415 TI - Conversion of nitrite to nitric oxide at zinc via S-nitrosothiols. AB - Nitrite is an important reservoir of nitric oxide activity in the plasma and cells. Using a biomimetic model, we demonstrate the conversion of zinc-bound nitrite in the tris(pyrazolyl)borate complex (iPr2)TpZn(NO2) to the corresponding S-nitrosothiol RSNO and zinc thiolate (iPr2)TpZn-SR via reaction with thiols H SR. Decomposition of the S-nitrosothiol formed releases nitric oxide gas. PMID- 24217412 TI - Antimalarial drug discovery - approaches and progress towards new medicines. AB - Malaria elimination has recently been reinstated as a global health priority but current therapies seem to be insufficient for the task. Elimination efforts require new drug classes that alleviate symptoms, prevent transmission and provide a radical cure. To develop these next-generation medicines, public private partnerships are funding innovative approaches to identify compounds that target multiple parasite species at multiple stages of the parasite life cycle. In this Review, we discuss the cell-, chemistry- and target-based approaches used to discover new drug candidates that are currently in clinical trials or undergoing preclinical testing. PMID- 24217416 TI - Pancreatic duct stents at pancreaticoduodenectomy: a meta-analysis. AB - BACKGROUND AND OBJECTIVE: Several studies suggested that pancreatic stents had some benefit during pancreatoduodenectomy (PD), but others disagree. Whether pancreatic duct stents could prevent postoperative pancreatic fistula (POPF) is still under controversy. METHODS: Randomized controlled trials published before November 2012 were all aggregated, focusing on the evaluation of pancreatic duct stents during PD. Trial data was reviewed and extracted independently by two reviewers. The quality of the including studies was assessed by the Cochrane handbook 5.1.0. RESULTS: Seven studies were included, with a total of 793 patients. The results showed that compared with nonstents, stents during PD was associated with a significant difference on overall POPF rate (OR = 0.65, 95% CI 0.45-0.95, p = 0.02), POPF grades B and C (OR = 0.45, 95% CI 0.27-0.76, p = 0.003), and hospital stay (MD = -4.28, 95% CI -6.81, -1.75, p = 0.0009). Subgroup analyses showed that the external stent had a significant difference in the incidence of overall POPF (OR = 0.46, 95% CI 0.29-0.73, p = 0.0009), POPF grades B and C (OR = 0.49, 95% CI 0.30-0.79, p = 0.003), postoperative morbidity (OR = 0.63, 95% CI 0.42-0.96, p = 0.03), as well as hospital stay. CONCLUSIONS: Based upon this meta-analysis, there might be potential benefit in reducing POPF thanks to the use of pancreatic duct stents. PMID- 24217413 TI - A decade after SARS: strategies for controlling emerging coronaviruses. AB - Two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and are associated with high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains is a research priority. In this Review, we describe the emergence and identification of novel human coronaviruses over the past 10 years, discuss their key biological features, including tropism and receptor use, and summarize approaches for developing broadly effective vaccines. PMID- 24217417 TI - Characterization of fetal cells from the maternal circulation by microarray gene expression analysis--could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis? AB - INTRODUCTION: Circulating fetal cells in maternal blood provide a tool for risk free, non-invasive prenatal diagnosis. However, fetal cells in the maternal circulation are scarce, and to effectively isolate enough of them for reliable diagnostics, it is crucial to know which fetal cell type(s) should be targeted. MATERIALS AND METHODS: Fetal cells were enriched from maternal blood by magnetic activated cell sorting using the endothelial cell marker CD105 and identified by XY fluorescence in situ hybridization. Expression pattern was compared between fetal cells and maternal blood cells using stem cell microarray analysis. RESULTS: 39 genes were identified as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the placenta, especially in extravillous trophoblasts (EVTs). Immunohistochemical staining of placental tissue confirmed CD105 staining in EVTs and 76% of fetal cells enriched by CD105 were found to be cytokeratin-positive. DISCUSSION: The unique combination of mesodermal (CD105) and ectodermal (cytokeratin) markers in EVTs could be a potential marker set for cell enrichment of this cell type in maternal blood and could be the basis for future cell-based non-invasive prenatal diagnosis. PMID- 24217418 TI - Prenatal diagnosis of umbilical artery thrombosis. AB - Umbilical artery thrombosis (UAT) is rare and few prenatally diagnosed cases have been reported. We describe 2 cases of fetal growth restriction prenatally diagnosed as UAT by ultrasound examination. In each case the cross section of the umbilical cord showed one normal artery and a small echogenic area which was suspected as an occluded thrombotic artery and they were surrounded by a highly curving 'C-shaped' vein. UAT was confirmed by histological examinations after deliveries in both cases. The characteristic ultrasound finding of the umbilical vessel, which is the so-called 'orange grabbed sign', enables the prenatal diagnosis of UAT and it is valuable with respect to perinatal fetal management because UAT is associated with increased perinatal morbidity and mortality. PMID- 24217419 TI - Oxidative C-H amination reactions. AB - Towards "Oxidative-Ullmann-Goldberg" and "Oxidative-Buchwald-Hartwig" type amination reactions. This review focuses on the newly developed oxidative C-N bond formation techniques, applicable in the field of organic synthesis. Particular emphasis is given to those which are classified as cross dehydrogenative-couplings, through dual C-H and N-H activation, thus formally extruding "H2" as a by-product. PMID- 24217421 TI - Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force. AB - BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor beta-carotene prevented CVD or cancer, and beta-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 24217422 TI - An on-chip coupled resonator optical waveguide single-photon buffer. AB - Integrated quantum optical circuits are now seen as one of the most promising approaches with which to realize single-photon quantum information processing. Many of the core elements for such circuits have been realized, including sources, gates and detectors. However, a significant missing function necessary for photonic quantum information processing on-chip is a buffer, where single photons are stored for a short period of time to facilitate circuit synchronization. Here we report an on-chip single-photon buffer based on coupled resonator optical waveguides (CROW) consisting of 400 high-Q photonic crystal line-defect nanocavities. By using the CROW, a pulsed single photon is successfully buffered for 150 ps with 50-ps tunability while maintaining its non classical properties. Furthermore, we show that our buffer preserves entanglement by storing and retrieving one photon from a time-bin entangled state. This is a significant step towards an all-optical integrated quantum information processor. PMID- 24217423 TI - A case of recurrent familial male miscarriages with hypercoiled umbilical cord: a possible X-linked association? PMID- 24217424 TI - Ribavirin protects Syrian hamsters against lethal hantavirus pulmonary syndrome- after intranasal exposure to Andes virus. AB - Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 ug/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route. PMID- 24217425 TI - A quantitative polymerase chain reaction test to enumerate leukocytes in allograft tissue and the implications for donor eligibility testing. AB - A country-to-country analysis of infectious disease screening requirements for donated tissues or cells reveals they are not often harmonized. Transmission of one such infectious disease, human T-lymphotropic virus (HTLV), is related to the transfer of HTLV-infected, viable leukocytes of sufficient number. The ability to characterize allograft tissue as being absent of leukocytes, or containing relatively few leukocytes, by using a specific test has not been previously investigated. A quantitative polymerase chain reaction (qPCR) test was developed to interrogate protein tyrosine phosphatase, receptor type C (PTPRC) gene expression in tissue samples and was able to determine the number of leukocytes present in a tissue. The impact of a qualified leukocyte tissue testing method should be significant and lead to changes in donor eligibility regulations in certain countries. Human leukapheresis samples were used as a control to establish the amount of PTPRC in leukocytes. That value was used as a comparator to determine the number of leukocyte equivalents in tissues of interest. The qPCR test measured tissue leukocyte equivalents and the results were consistent with the relative abundance of leukocytes predicted for each tissue. Using qPCR to calculate leukocyte equivalents based upon PTPRC gene expression can be successfully employed to estimate the number of leukocytes in a tissue or allograft. This method could be used as a screen to rule out tissues that do not meet the criteria of being leukocyte rich and, therefore, do not need direct HTLV testing. PMID- 24217427 TI - Iron(III) sulfate: a stable, cost effective electrode material for sodium ion batteries. AB - Iron(iii) sulfate, a rhombohedral NASICON compound, has been demonstrated as a sodium intercalation host. This cost-effective material is attractive, as it can be slurry processed in bulk with ball-milling, while utilizing the iron 2(+)/3(+) redox couple, offering stable 3.2 V performance for over 400 cycles. PMID- 24217426 TI - The association between physical activity and eating self-regulation in overweight and obese women. AB - OBJECTIVE: Successful weight management relies heavily on eating and exercise behaviors. However, little is known about the association between both on a psychosocial level. This study examined the relationship between exercise and eating regulation by exploring the mediating effects of negative body image investment and depressive mood, and their stability through time. METHODS: Analyses were conducted at two different moments (12 and 36 months), involving a sample of 221 overweight/obese women (age: 37.6 +/- 7 years; BMI: 31.6 +/- 4.1 kg/m(2)) that participated in a behavioral weight control intervention. Bivariate correlations and mediation analyses using Preacher & Hayes resampling procedures were conducted. RESULTS: At 12 months, negative body image investment was the only significant mediator of the exercise-eating relationship. This variable explained larger portions of the indirect effects of structured rather than lifestyle exercise on eating. At 36 months, negative investment and to a lesser extent depressive mood partially explained the exercise-eating association. CONCLUSIONS: Our findings suggest that, besides physiological effects of exercise, psychological mechanisms related to body image and mood also explain the role of physical activity as a 'gateway behavior' for improved eating regulation in overweight women. These effects appear to be stable and may help understand the key role of exercise in long-term weight management. PMID- 24217428 TI - Validation of an automated dose-dispensing system for 18F-FDG administrations and associated reduction in operator extremity dose. AB - OBJECTIVE: The current procedure at our centre for partitioning multidose vials of fluorine-18-fluorodeoxyglucose (F-FDG) is based on a manual method. To reduce extremity dose while reducing contamination risk, maintaining product sterility and improving the accuracy of injected activity, we recently purchased a new semiautomated partitioning system (MUDDS-A). This work reports on the operating characteristics of the system and its validation for clinical use in terms of dispensing accuracy and extremity dose reduction. METHODS: A range of operators carried out 300 automated partitioning procedures by following a typical working day setup. The accuracy of the activity resulting from system partitioning compared with true syringe activity was determined. We also determined the precision of system-determined activity when compared with user-requested activity. The cumulative finger dose for automated and manual partitioning techniques was measured at the fingertip using a digital dosimeter, recording the dose at different stages of the procedure. RESULTS: The results of comparisons made between the final syringe activity measured by the system and the measurement of the true syringe activity independently of the system were within +/-5% for 96.63% of syringes. Precision of the syringe activity provided by the system with respect to the user-requested activity was within +/-10% for 96.96% of measurements. Average finger doses compared with a manual partitioning method showed a reduction of up to 80% when relying only on the system measurement of activity. CONCLUSION: The MUDDS-A reproducibly partitions a vial of F-FDG and offers a significant reduction in extremity dose to the operator of up to 80% in comparison with a manual partition technique. PMID- 24217429 TI - Dual malignancies in the setting of differentiated thyroid carcinoma: their synchronous or metachronous nature, impact of radioiodine treatment on occurrence of second malignancy and other associated variables. AB - PURPOSE: The primary objective of the study was to assess the risk for second primary malignancy after radioiodine treatment for differentiated thyroid carcinoma (DTC). Other objectives were to study the different variables associated with the occurrence of synchronous or metachronous dual malignancies in association with DTC. MATERIALS AND METHODS: The patient population studied comprised patients with histopathologically proven DTC referred for radioactive iodine treatment after thyroidectomy followed up at a single centre during the period from January 1963 to March 2011. The data collected were analysed with respect to different variables associated with two primary tumours in the setting of DTC. RESULTS: Out of the total 8614 patients studied from 1963 to March 2011, 44 dual malignancies in association with DTC were detected, showing a prevalence rate of 0.5%. The most common site of second primary malignancy was the head and neck (H&N) in men and the breast in women. Of the 44 dual malignancies, 18 were synchronous in nature and 26 were metachronous. In the metachronous group, thyroid carcinoma was the first primary malignancy in only 5/26 patients, whereas the remaining 21 patients had thyroid carcinoma as the second primary malignancy. In 5/26 patients in whom carcinoma of the thyroid was the first primary malignancy, the second primary malignancy was breast carcinoma in two cases, renal cell carcinoma in one case, colorectal carcinoma in one case and metastatic NET of unknown primary in one case. All these five patients received radioiodine treatment with different activities. In 21/26 patients in whom thyroid carcinoma was the second primary malignancy, the most common first primary malignancy comprised H&N tumours. In this group, 12 patients had a history of external beam radiotherapy (EBRT). Among synchronous malignancies (18/44 patients), H&N tumours were the most commonly associated. CONCLUSION: There was no significant risk for second primary malignancy after radioactive iodine treatment in patients with DTC. There is increased risk for thyroid malignancy after EBRT delivered for other primary tumours, especially in children. Hence, any thyroid abnormality on long-term follow-up of patients after EBRT for other tumours should be considered carefully. H&N malignancies are the most common synchronous, metachronous and overall associated second malignancy with thyroid carcinoma. PMID- 24217430 TI - Improved visualization of perfusion defects by respiratory-gated SPECT: a phantom simulation study. AB - OBJECTIVES: Single-photon emission computed tomography ventilation/perfusion (SPECT V/Q) imaging is recommended both by the Society of Nuclear Medicine and by the European Association of Nuclear Medicine for the diagnosis of pulmonary embolism. However, respiratory motion produces image blurring and degradation of detail in the lungs. We have investigated respiratory gating of SPECT images, correcting for motion to reduce blur and improve image definition. MATERIALS AND METHODS: Wedge-shaped defects of different sizes ranging from 15 to 4 mm were fixed in the lung cavities of an anthropomorphic lung phantom to simulate perfusion defects. Gated and nongated SPECT images were obtained using a double headed SPECT system. Three-dimensional movement was introduced using a purpose built moving platform with two motion frequencies of 10 and 20 cycles/min. Motion was tracked with a respiratory-gating system. Gated SPECT data were acquired in 16 discrete data bins in synchronization with the breathing cycle. The images were reconstructed using ordered-subset expectation maximization algorithms and corrected for rigid motion. Contrast and contrast-to-noise ratios (CNRs) were measured to quantify any improvement in the gated motion-corrected images. Visualization of defects in the reconstructed images was performed by seven observers and analyzed using alternative free-response receiver operating characteristic analysis. RESULTS: Assessment of gated and nongated SPECT phantom images demonstrated that motion adversely affected the detectability of defects. Quantification of data demonstrated that, in the controlled simulation, image quality, defect definition, observer confidence, contrast, and CNR were increased after applying motion correction. Improvement in CNRs was found to be significant using alternative free-response receiver operating characteristic analysis (P=0.0002). CONCLUSION: Respiratory-gated motion-corrected SPECT images enhanced the visualization of defects compared with matched moving/nongated images in a realistic moving phantom. This approach may be particularly valuable for SPECT V/Q imaging and may improve the diagnosis of pulmonary embolism. PMID- 24217432 TI - Impact on Hypertension Reclassification by Ambulatory Blood Pressure Monitoring (ABPM) according to the V Brazilian Guidelines on ABPM. PMID- 24217433 TI - Prognostic factors in patients with acute coronary syndrome without ST-segment elevation. PMID- 24217434 TI - Case 5/2013 - a four-year-old boy with a rhabdomyoma-type cardiac tumor in both ventricles and repeated ventricular tachycardia. PMID- 24217435 TI - Renal denervation by ablation with innovative technique in resistant hypertension. PMID- 24217436 TI - Exuberant pattern of late gadolinium enhancement in hypertrophic cardiomyopathy. PMID- 24217437 TI - Paternalism, autonomy and ontology. PMID- 24217439 TI - India should introduce daily drug treatment for tuberculosis. PMID- 24217438 TI - Characterization of the interaction between Toxoplasma gondii rhoptry neck protein 4 and host cellular beta-tubulin. AB - Toxoplasma rhoptry neck protein 4 (TgRON4) is a component of the moving junction macromolecular complex that plays a central role during invasion. TgRON4 is exposed on the cytosolic side of the host cell during invasion, but its molecular interactions remain unclear. Here, we identified host cellular beta-tubulin as a binding partner of TgRON4, but not Plasmodium RON4. Coimmunoprecipitation studies in mammalian cells demonstrated that the C-terminal 15-kDa region of beta-tubulin was sufficient for binding to TgRON4, and that a 17-kDa region in the proximal C terminus of TgRON4 was required for binding to the C-terminal region of beta tubulin. Analysis of T. gondii-infected lysates from CHO cells expressing the TgRON4-binding region showed that the C-terminal region of beta-tubulin interacted with TgRON4 at early invasion step. Our results provide evidence for a parasite-specific interaction between TgRON4 and the host cell cytoskeleton in parasite-infected cells. PMID- 24217440 TI - Syrian refugees could bring polio to Europe, experts warn. PMID- 24217441 TI - TB activists at world conference boo Indian minister off stage. PMID- 24217442 TI - Insurers are required to offer coverage for mental problems similar to that for physical ones. PMID- 24217443 TI - Canada must do more to tackle poorer health of indigenous people, says national chief. PMID- 24217445 TI - The association between bullying and physical health among gay, lesbian, and bisexual individuals. AB - BACKGROUND: Research suggests that lesbian, gay, and bisexual (LGB) populations experience higher prevalence of school bullying than heterosexuals. OBJECTIVES: We examined if (a) verbal versus physical bullying were differentially associated with physical health among sexual minorities and (b) if sexual identity (i.e., homosexual [i.e., lesbian/gay] vs. bisexual) moderated the association of bullying on physical health. DESIGN: LGB adults aged 18 to 66 years (n = 463) were recruited online. Participants reported high school experiences of verbal and physical bullying and physician-diagnosed health conditions. RESULTS: Physical and verbal bullying were related to physical health conditions (ps < .01). Physical bullying had a significant negative impact on physical health for bisexual persons (p < .001) but not for gay/lesbian persons. CONCLUSIONS: Experiencing bullying in high school was associated with physical health problems in adulthood. Bullying had a different relationship with health problems for bisexually identified individuals compared to lesbian/gay individuals. Future research should strive to disentangle potential differences in the relationship between bullying and health within sexual minority groups. PMID- 24217444 TI - The second extracellular loop of the adenosine A1 receptor mediates activity of allosteric enhancers. AB - Allosteric enhancers of the adenosine A1 receptor amplify signaling by orthosteric agonists. Allosteric enhancers are appealing drug candidates because their activity requires that the orthosteric site be occupied by an agonist, thereby conferring specificity to stressed or injured tissues that produce adenosine. To explore the mechanism of allosteric enhancer activity, we examined their action on several A1 receptor constructs, including (1) species variants, (2) species chimeras, (3) alanine scanning mutants, and (4) site-specific mutants. These findings were combined with homology modeling of the A1 receptor and in silico screening of an allosteric enhancer library. The binding modes of known docked allosteric enhancers correlated with the known structure-activity relationship, suggesting that these allosteric enhancers bind to a pocket formed by the second extracellular loop, flanked by residues S150 and M162. We propose a model in which this vestibule controls the entry and efflux of agonists from the orthosteric site and agonist binding elicits a conformational change that enables allosteric enhancer binding. This model provides a mechanism for the observations that allosteric enhancers slow the dissociation of orthosteric agonists but not antagonists. PMID- 24217446 TI - The Patient Protection and Affordable Care Act: impact on mental health services demand and provider availability. AB - The Patient Protection and Affordable Care Act (ACA) will greatly increase the demand for mental health (MH) services, as 62.5 million Americans from relatively high-need populations will be newly eligible for MH benefits. Consequently, the supply of MH care provider services is expected to proportionately decrease by 18% to 21% in 2014. ACA funding does not demonstrate the ability to increase turnout of psychiatrists sufficiently to meet the need. Available data indicate that the numbers of advanced practice psychiatric nurses (APPNs) continue to increase at a much greater rate, but information from either a clinical perspective or a market perspective is complicated by the weak distinctions that are made between nurse practitioners (NPs) and other nonphysician care professionals. The following recommendations are made: (a) some of the ACA funding for research into efficient and effective care delivery systems should be allocated to acquiring data on APPNs in leadership roles or clinical settings in which they are ultimately responsible for management of MH care, as differentiated from settings in which they provide support for psychiatrists; and (b) since the available data indicate nurse practitioners achieve good outcomes and are more economically viable than psychiatrists, placement of psychiatric mental health nurse practitioners in community settings should be recognized as a realistic solution to the shortfall of MH services. PMID- 24217447 TI - Demographic, psychosocial, and contextual factors associated with sexual risk behaviors among young sexual minority women. AB - Young sexual minority women are at risk for negative sexual health outcomes, including sexually transmitted infections and unintended pregnancies, yet little is known about these risks. We examined factors that may influence sexual risk from a psychosocial and contextual perspective. Analyses were conducted to examine within group relationships between sexual behaviors, negative outcomes, and related factors in a sample of young sexual minority women. Participants (N = 131) were young (mean = 19.8) and diverse in terms of race/ethnicity (57% non White). Sex under the influence, having multiple partners, and having unprotected sex were common behaviors, and pregnancy (20%) and sexually transmitted infection (12%) were common outcomes. Risk behaviors were associated with age, alcohol abuse, and older partners. Results support the need for further research to understand how these factors contribute to risk in order to target risk reduction programs for this population. PMID- 24217450 TI - Indium(III) triflate-catalysed [4 + 2] benzannulation reactions of o alkynylbenzaldehydes with enolisable carbonyl compounds: selective synthesis of naphthyl ketones. AB - Indium(III) triflate is found to be an effective catalyst for the benzannulation reactions of o-alkynylbenzaldehydes with enolisable aldehydes, ketones, 1,3 diketones and beta-keto esters. The reactions produce naphthyl ketones through ring opening of adducts arising from the inverse electron demand Diels-Alder reactions between in situ generated isochromenylium cations and enols. The main feature of the method is selective formation of naphthyl ketones in a highly regioselective manner without any decarbonylation. PMID- 24217448 TI - Changes in neighborhood characteristics and depression among sexual minority young adults. AB - Using the National Longitudinal Study of Adolescent Health, this study examined the relationship between changes in neighborhood characteristics during the transition from adolescence to young adulthood and depression among sexual minority young adults. Previous research has found that neighborhood characteristics influence sexual minority mental health and that sexual minorities are more likely to move to more urban and politically liberal locations. No study to date, however, has examined the impact of changes in neighborhood characteristics on sexual minority depression. The results from this study show that decreases in the percent urban was associated with increased risk of depression and decreases in the percent Republican voters in sexual minority's neighborhood was associated with decreases in risk of depression. The results suggest that clinicians may want to screen sexual minority youth for recent changes in their neighborhoods to assess if these changes may be related to the onset or exacerbation of depressive episodes. PMID- 24217453 TI - Challenges of making music: what causes musician's dystonia? PMID- 24217454 TI - Chronic lymphocytic inflammation with Pontine perivascular enhancement responsive to steroids and fatal B-cell lymphoma. PMID- 24217455 TI - Chronic lymphocytic inflammation with Pontine perivascular enhancement responsive to steroids and fatal B-cell lymphoma--reply. PMID- 24217459 TI - Acute kidney injury: Short-term statin therapy for prevention of contrast-induced AKI. AB - Two recent studies suggest that periprocedural statin administration can prevent contrast-induced acute kidney injury in cardiac patients undergoing percutaneous coronary intervention and in renal patients undergoing angiography, with or without intervention. These studies support the routine administration of potent statins before contrast media infusion in these vulnerable patients. PMID- 24217457 TI - Psychometric properties of the Cannabis Abuse Screening Test in Hungarian samples of adolescents and young adults. AB - AIM: The aim of our study was to analyze psychometric properties of the Cannabis Abuse Screening Test (CAST). METHODS: Our sample comprised Hungarian high school (n = 476; male 56.3%; mean age 19.0 years, SD = 0.65 years) and college students (n = 439; male 65.1%; mean age 23.9 years, SD = 1.56 years) who reported cannabis use in the past year. The sample covered the five biggest universities of Hungary. Besides the CAST, participants responded to the Munich-Composite International Diagnostic Interview. Factor structure was analyzed by a confirmatory factor analysis. Receiver operating characteristic curve analysis was made to assess cut-off scores. Data collection took place in 2010. RESULTS: CAST proved to be a reliable (Cronbach's alpha 0.71 and 0.76) one-dimensional measure. Regarding both cannabis dependence and cannabis use disorders, a cut-off of 2 points proved to be ideal in both samples, resulting in optimal specificity, negative predictive values and accuracy, but less than optimal positive predictive values (dependence) and low sensitivity (cannabis use disorder). DISCUSSION AND CONCLUSIONS: In line with former results, the CAST proved to be an adequate measure for the screening of cannabis-related problems among adolescents and young adults in an Eastern European country where this scale has not been studied before. PMID- 24217462 TI - Basic research: Podocyte progenitors and ectopic podocytes. AB - Two types of parietal podocyte were previously described in the Bowman capsule: one characterized by coexpression of podocyte and parietal epithelial cell markers, the other characterized by expression of podocyte markers only. New research demonstrates that these populations represent podocyte progenitors and ectopic podocytes-distinct cell types with different clinical implications. PMID- 24217466 TI - Stratonovich-to-Ito transition in noisy systems with multiplicative feedback. AB - Intrinsically noisy mechanisms drive most physical, biological and economic phenomena. Frequently, the system's state influences the driving noise intensity (multiplicative feedback). These phenomena are often modelled using stochastic differential equations, which can be interpreted according to various conventions (for example, Ito calculus and Stratonovich calculus), leading to qualitatively different solutions. Thus, a stochastic differential equation-convention pair must be determined from the available experimental data before being able to predict the system's behaviour under new conditions. Here we experimentally demonstrate that the convention for a given system may vary with the operational conditions: we show that a noisy electric circuit shifts from obeying Stratonovich calculus to obeying Ito calculus. We track such a transition to the underlying dynamics of the system and, in particular, to the ratio between the driving noise correlation time and the feedback delay time. We discuss possible implications of our conclusions, supported by numerics, for biology and economics. PMID- 24217467 TI - Construction of chromosome markers from the Lake Victoria cichlid Paralabidochromis chilotes and their application to comparative mapping. AB - Cichlid fishes in the African Great Lakes are known as a spectacular example of adaptive radiation in vertebrates. Four linkage maps have been constructed to identify the genes responsible for adaptation and speciation, and the genetic linkages of those genes are assumed to play an important role during adaptive evolution. However, it is difficult to analyze such linkages because the linkage groups of one species do not match well with those of the other species. Chromosome markers are a powerful tool for the direct identification of linkage homology between different species. We used information about the linkage map of the Lake Malawi cichlid (Labeotropheus fuelleborni/Metriaclima zebra) to isolate bacterial artificial chromosome (BAC) clones from the BAC library of Paralabidochromis chilotes, Lake Victoria. We identified 18 of 22 P. chilotes chromosomes by single- and multi-color BAC fluorescence in situ hybridization using 19 BAC clones. Comparative mapping with the chromosome markers of P. chilotes in Astatotilapia burtoni (2n = 40) from Lake Tanganyika revealed the chromosome rearrangements that have occurred in this lineage. These chromosome markers will be useful for delineating the process of genome and chromosome evolution in African species. PMID- 24217464 TI - Fluid management for the prevention and attenuation of acute kidney injury. AB - In patients with acute kidney injury (AKI), optimization of systemic haemodynamics is central to the clinical management. However, considerable debate exists regarding the efficacy, nature, extent and duration of fluid resuscitation, particularly when the patient has undergone major surgery or is in septic shock. Crucially, volume resuscitation might be required to maintain or restore cardiac output. However, resultant fluid accumulation and tissue oedema can substantially contribute to ongoing organ dysfunction and, particularly in patients developing AKI, serious clinical consequences. In this Review, we discuss the conflict between the desire to achieve adequate resuscitation of shock and the need to mitigate the harmful effects of fluid overload. In patients with AKI, limiting and resolving fluid overload might prompt earlier use of renal replacement therapy. However, rapid or early excessive fluid removal with diuretics or extracorporeal therapy might lead to hypovolaemia and recurrent renal injury. Optimal management might involve a period of guided fluid resuscitation, followed by management of an even fluid balance and, finally, an appropriate rate of fluid removal. To obtain best clinical outcomes, serial fluid status assessment and careful definition of cardiovascular and renal targets will be required during fluid resuscitation and removal. PMID- 24217468 TI - Histological evaluation to study the effects of dental amalgam and composite restoration on human dental pulp: an in vivo study. AB - OBJECTIVE: To study and compare the effects of dental amalgam and composite restorations on human dental pulp. MATERIALS AND METHODS: One hundred sound premolars scheduled for orthodontic extraction were divided equally into two groups: group A, teeth restored with silver amalgam, and group B, teeth restored with composite resin. Each group was equally subdivided into two subgroups [extracted after 24 h (A-1 and B-1) or 7 days (A-2 and B-2)], and the histological changes in the pulp related to the two different materials at the two different intervals were studied. RESULTS: It was found that after 24 h, the inflammatory response of the pulp in teeth restored with amalgam and composite was similar (p = 1.00). However, after 7 days, the severity of the inflammatory response of the pulp in teeth restored with amalgam was less compared to that in teeth restored with composite (p = 0.045). CONCLUSION: This study confirmed that amalgam continues to be the mechanically as well as biologically more competent restorative material. Composite could be a promising restorative material to satisfy esthetic needs for a considerable period of time. However, its biological acceptance is still in doubt. PMID- 24217469 TI - Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. AB - BACKGROUND: Deaths due to prescription opioid overdoses have increased dramatically. High-quality guidelines could help clinicians mitigate risks associated with opioid therapy. PURPOSE: To evaluate the quality and content of guidelines on the use of opioids for chronic pain. DATA SOURCES: MEDLINE, National Guideline Clearinghouse, specialty society Web sites, and international guideline clearinghouses (searched in July 2013). STUDY SELECTION: Guidelines published between January 2007 and July 2013 addressing the use of opioids for chronic pain in adults were selected. Guidelines on specific settings, populations, and conditions were excluded. DATA EXTRACTION: Guidelines and associated systematic reviews were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument and A Measurement Tool to Assess Systematic Reviews (AMSTAR), respectively, and recommendations for mitigating opioid-related risks were compared. DATA SYNTHESIS: Thirteen guidelines met selection criteria. Overall AGREE II scores were 3.00 to 6.20 (on a scale of 1 to 7). The AMSTAR ratings were poor to fair for 10 guidelines. Two received high AGREE II and AMSTAR scores. Most guidelines recommend that clinicians avoid doses greater than 90 to 200 mg of morphine equivalents per day, have additional knowledge to prescribe methadone, recognize risks of fentanyl patches, titrate cautiously, and reduce doses by at least 25% to 50% when switching opioids. Guidelines also agree that opioid risk assessment tools, written treatment agreements, and urine drug testing can mitigate risks. Most recommendations are supported by observational data or expert consensus. LIMITATION: Exclusion of non-English-language guidelines and reliance on published information. CONCLUSION: Despite limited evidence and variable development methods, recent guidelines on chronic pain agree on several opioid risk mitigation strategies, including upper dosing thresholds; cautions with certain medications; attention to drug-drug and drug-disease interactions; and use of risk assessment tools, treatment agreements, and urine drug testing. Future research should directly examine the effectiveness of opioid risk mitigation strategies. PRIMARY FUNDING SOURCE: California Department of Industrial Relations and California Commission on Health and Safety and Workers' Compensation. PMID- 24217470 TI - Treatment of advanced cutaneous squamous cell carcinomas with epidermal growth factor receptor inhibitors. AB - In advanced cutaneous squamous cell carcinoma (cSCC), efficient medical treatment options are limited in case surgery and radiotherapy failed, particularly since most patients are of higher age and suffer from comorbidities. In many tumor entities, the epidermal growth factor receptor (EGFR) has been established as an important therapeutic target, and blockade of EGFR signaling by monoclonal antibodies or small molecules achieves a therapeutic benefit. EGFR expression is also often dysregulated in cSCC. We report here two patients with advanced cSCC treated with the EGFR inhibitor cetuximab and summarize the current published experience with the use of EGFR inhibitors in cSCC. PMID- 24217472 TI - Enantioselective desymmetrization of prochiral 1,3-dinitropropanes via organocatalytic allylic alkylation. AB - An enantioselective desymmetrization of prochiral 1,3-dinitropropanes has been developed which proceeds via enantiogroup differentiating organocatalytic allylic alkylation. Densely functionalized products with two vicinal stereocenters were obtained generally with good to excellent diastereoselectivity (up to >20 : 1 dr) and superb enantioselectivity (up to >99 : 1 er). PMID- 24217471 TI - BMI and BAI as markers of obesity in a Caucasian population. AB - BACKGROUND: BMI is known to have limited accuracy, which is different for males and females with similar body fat content. That is why Bergman et al. (Obesity 2011;19:1083-1089) introduced an alternative variable of obesity, called the body adiposity index (BAI). Their primary research was conducted in samples of Mexican American and African-American populations. The objective of our research was to investigate the sex-specific relationship between both BMI and BAI and body fat content in a healthy Caucasian population. The accuracy of both indexes was compared. METHODS: 684 women and 528 men aged 20-22 years with Caucasian origin only participated in the study. Participants were students of universities in southern Poland. They had no indication of cardiometabolic problems, as evaluated by interview. RESULTS: The study revealed that BAI is a more sensitive method in assessing obesity in Caucasian males rather than BMI. In the population of Caucasian women BAI results indicate a significant underestimation of obesity. CONCLUSION: The fact that there is a high statistical correlation between BAI and % fat mass among obese and overweight men and women suggests that BAI could be highly specific provided that the BAI cutoffs will be adapted to the European population. PMID- 24217473 TI - Apocrine adenocarcinoma of the eyelid: case series and review. AB - PURPOSE: To report 2 patients with apocrine adenocarcinoma of the eyelid and review the literature. DESIGN: Noncomparative, retrospective case series and review. PARTICIPANTS: Clinical data of 2 patients with histopathologic diagnoses of apocrine adenocarcinoma of the eyelid were obtained from medical records. The histopathology and immunohistochemistry data for the 2 cases were studied. A retrospective review was performed on all reported cases of eyelid apocrine carcinoma. MAIN OUTCOME MEASURES: Clinical features, histopathology, immunohistochemistry, and clinical course following treatment are reported. The results of a retrospective review of clinical presentations, local and systemic spread, treatment method, and prognosis from published case reports on eyelid apocrine adenocarcinoma are discussed. RESULTS: One patient had orbital invasion at presentation. This patient had radiotherapy alone and had no systemic or local recurrence at 2 years. One patient underwent a 4-mm margin wide surgical excision. This patient had no local or systemic recurrences at 1 year. A review of the literature suggests that the prognosis of adnexal apocrine tumors is indeterminate and variable. Most patients have successful outcomes following local surgical excision. Radiotherapy has been used as an adjunctive treatment for local metastatic disease. CONCLUSIONS: Apocrine adenocarcinoma is a rare adnexal tumor of the eyelid, which may present with orbital invasion. PMID- 24217474 TI - Comparison of methodologies in volumetric orbitometry. AB - PURPOSE: The rate at which the orbit matures is not well-documented. Limiting this pursuit are the difficulties inherent in measuring orbital volumes accurately. This study compared 3 common methods of determining orbital volume and sought to identify an accurate, practical manner for doing so. METHODS: The volume of 1 orbit of 8 human cadaver heads was independently measured using 3 different methods: 1) CT was performed, and images were analyzed with 3 dimensional (3D) volumetric software; 2) The same orbits were then exenterated and a silicone cast was taken. The cast volumes were measured by water displacement; 3) The orbits were then filled with 1-mm glass beads that were transferred to a graduated cylinder where their volume was determined. The data were analyzed statistically. RESULTS: Intraobserver agreements were good for both beads and casts. Interobserver agreements were good for both beads and CT (p > 0.05). Values obtained using the bead method were equal to values obtained using the cast method (p > 0.05). However, agreement between direct (orbital fillers and casts) and indirect measurements (radiographic techniques) was not satisfactory (p < 0.05). CONCLUSIONS: Independent of method, determining orbital volume is inherently difficult owing to the hyperbolic parabola that is the orbit entrance; all methods require estimation. Glass beads and casts yielded more reproducible values but can only be used in cadavers. CT measurement is prone to error due to the variability of methodologies used but allows access to enormous testing populations. Interstudy comparison is currently not possible. CT volumetric software with strict universal standards for estimating the anterior limit of the orbit appears to be the best method of studying human orbital volumes. PMID- 24217475 TI - Efficacy of temperature-sensitive Guardix-SG for adhesiolysis in experimentally induced eyelid adhesion in rabbits. AB - PURPOSE: To determine the efficacy of a temperature-sensitive poloxamer/alginate mixture (Guardix-SG) for reducing adhesions after blepharoplasty in rabbit models. METHODS: Thirty-six intact eyes of 18 rabbits were randomly designated to 2 groups, and primary blepharoplasty was performed on both the upper eyelids of the 18 rabbits. Sterile cotton soaked in 1 N NaOH was used to produce chemical tissue damage to experimentally induce eyelid adhesion, which was followed by adhesiolysis in 2 weeks. During adhesiolysis, Guardix-SG was applied to the OD of rabbits in the experimental group, while adhesiolysis alone was performed on the OS of rabbits in the control group. Both sides were compared by gross examination 1 day, 1 week, and 4 weeks after surgery, and the degrees of inflammation and fibrosis were examined with hematoxylin-eosin (H&E) and Masson's trichrome (MT) stains. The expression of alpha-smooth muscle actin (alpha-SMA) antibody was also immunohistochemically examined. RESULTS: The gross examinations performed after adhesiolysis yielded results that were not significantly different between the experimental and the control groups, and no prevalent complications, such as eyelid traction or distorted eyelids, were observed. One day (p = 0.028), 1 week (p = 0.028), and 4 weeks (p = 0.028) after surgery, the experimental group had a lower infiltration rate of inflammatory cells than the control group, as shown by H&E staining. The MT staining and alpha-SMA staining also showed that the collagen deposition and fibrosis (1 week, p = 0.059; 4 weeks, p = 0.034) and the degree of myofibroblast differentiation were significantly lower in the experimental group than in the controls (1 week, p = 0.027; 4 weeks, p = 0.024). CONCLUSIONS: The temperature-sensitive poloxamer/alginate mixture (Guardix-SG) decreased inflammation and fibrosis after blepharoplasty and histopathologically prevented the readhesion of secondary blepharoplasty in rabbit models. Therefore, additional clinical studies are needed for other ophthalmic surgeries that could benefit from preventing postoperative adhesions. PMID- 24217476 TI - Canalicular wall dysgenesis: the clinical profile of canalicular hypoplasia and aplasia, associated systemic and lacrimal anomalies, and clinical implications. AB - PURPOSE: To report the clinical and diagnostic profile of canalicular wall dysgenesis (CWD), associated systemic and lacrimal anomalies and to propose its classification. METHODS: Prospective interventional study involving 7 dysgenetic canaliculi of 7 consecutive patients seen between June 2010 and July 2012. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, slit-lamp examination, punctal profiles, types of canalicular dysgenesis, wall involvement details, associated systemic and lacrimal anomalies, family history, and management modalities. CWD and its components were defined along with their clinical features. RESULTS: The patients included were 5 men and 2 women, with a mean age of 5.8 years (range 2-12 years) at presentation. All patients had unilateral and single canalicular involvement. Epiphora was the most common complaint noted in all the patients, and the symptoms were noticed since birth in 85.7% (6/7). The right eye was involved in 85.7% (6/7) and lower canaliculi were involved in 57.1% (4/7) of the cases. Isolated single wall dysgenesis involving only the roof was noted in 71.4% (5/7), with hypoplasia being the common form seen in 57.1% (4/7). Associated lacrimal anomalies were seen in all and systemic anomalies were noted in 28.5% (2/7) of the patients. CONCLUSIONS: This study exclusively describes the clinical profile of CWD and proposes a classification. Single or multiple canalicular wall hypoplasia and aplasia are probably better terms to use, and this study could be the beginning for further investigations into the embryogenesis and genetics of this intriguing congenital disorder. PMID- 24217477 TI - Mitomycin C in dacryocystorhinostomy: the search for the right concentration and duration--a fundamental study on human nasal mucosa fibroblasts. AB - PURPOSE: To establish primary cultures of human nasal mucosal fibroblasts (HNMFs) and to test the effect of varying concentrations of mitomycin C (MMC) and treatment durations on cellular proliferation and viability of the fibroblasts. DESIGN: Laboratory investigation. METHODS: Nasal mucosa harvested from patients undergoing a dacryocystorhinostomy was used to establish primary cultures by explant culture method. Cells were expanded and frozen at every passage, and passage 3 cells were used for further experiments. The cells were then treated with different concentrations of mitomycin C (0.1-0.5 mg/ml) for different time periods (3, 5, and 10 minutes). Cell viability was checked by MTT (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cellular proliferation index was determined with bromodeoxyuridine immunostaining. Apoptotic index was measured using annexin A5 affinity assay, propidium iodide staining, and 4',6-diamidino-2-phenylindole counterstaining. The actin cytoskeletons of fibroblasts were studied using phalloidin staining. RESULTS: The doubling time of cultured HNMFs is approximately 24 hours. Similarly, 0.4 mg/ml beyond 5 minutes and 0.5 mg/ml concentration at all time points were lethal and caused extensive cell death when compared with controls. A concentration of 0.2 mg/ml for 3 minutes of exposure prevented cell proliferation of HNMF cells by inducing cell cycle arrest, without causing extensive apoptosis. CONCLUSIONS: The minimum effective concentration appears to be 0.2 mg/ml for 3 minutes. This in vitro study could be the starting point for further clinical and histopathologic studies to validate its clinical usefulness. PMID- 24217478 TI - Volumetric rejuvenation of the tear trough with repo and Ristow. AB - PURPOSE: The authors report the results of their approach for the treatment of the tear trough deformity, by lower eyelid blepharoplasty with fat repositioning and fat transfer to Ristow's space and the deep medial fat compartment. METHODS: One hundred fourteen eyes of 57 patients underwent lower eyelid blepharoplasty, fat repositioning, and fat transfer between 2010 and 2012. RESULTS: No major complications were observed in any of the patients in this series. In all cases, there was significant improvement in the lower eyelid contour, tear trough, and blending of the transition at the eyelid-cheek junction noted by both patients and physicians. CONCLUSIONS: Despite the availability of multiple procedures, effacement of the tear trough region remains a challenge. The addition of fat transfer to Ristow's space and the deep medial fat compartment to traditional fat repositioning lower blepharoplasty are effective methods for volumizing the tear trough and may synergistically improve outcomes. PMID- 24217479 TI - Long-term histopathologic study of the frontalis muscle flap after frontalis suspension for severe ptosis repair. AB - PURPOSE: To investigate the long-term histopathologic changes of the frontalis muscle flap after frontalis muscle flap suspension for severe ptosis repair. METHODS: Eight 3-month miniature pigs were selected as the experimental animals, and self-comparison was used. The experimental side of the upper eyelid was constructed to have severe ptosis by resection of the levator aponeurosis, while the other side served as the control. Samples of the upper eyelid composite at 6 months and 12 months after ptosis repair were obtained and studied through light microscopy and transmission electron microscopy. RESULTS: The histopathologic study revealed that the frontalis muscle flap kept viable with normal muscular structure and direction 6 months and 12 months after the frontalis suspension procedure. CONCLUSIONS: The frontalis muscle flap appears to be a suitable material for frontalis suspension technique because of its feasibility and histopathologic stability. PMID- 24217480 TI - Relationship of horizontal lower eyelid laxity, involutional entropion occurrence, and age of Asian patients. AB - PURPOSE: To examine the relationship of horizontal lower eyelid laxity, frequency of involutional entropion occurrence, and age of Asian patients. METHODS: Three hundred seventy-six Japanese patients were examined (age range, 3-95 years). The horizontal laxity was examined with a pinch test. A pinch test of >8 mm was judged as positive. The percentage of entropion eyelids was calculated, and pinch tests were also performed. The percentage of entropion eyelids in the total positive pinch test eyelids was calculated. RESULTS: A positive pinch test first appeared around 40 years of age and increased with age: 7.4% at 50 to 59 years, 8.5% at 60 to 69 years, 18.1% at 70 to 79 years, 37.9% at 80 to 89 years, and 50.0% at >=90 years. The entropion first appeared around 60 years of age. All patients demonstrated unilateral entropion with a positive pinch test. The percentage of entropion occurrence showed an increase with age: 1.7% at 60 to 69 years, 2.6% at 70 to 79 years, 5.2% at 80 to 89 years, and 8.3% at >=90 years. The percentage of entropion eyelids in the total positive pinch test eyelids was 20.0% at 60 to 69 years, 14.3% at 70 to 79 years, 13.6% at 80 to 89 years, and 16.7% at >=90 years, and no significant difference was found among all ages (p = 0.985). CONCLUSIONS: Lower eyelid horizontal laxity and involutional entropion occurrence increased with age, and the latter was similar over ages when the pinch test was >8 mm. PMID- 24217481 TI - Intraoperative sub-tenon injection increases optic nerve length transection during enucleation. AB - PURPOSE: To determine the effect of sub-Tenon injection on the length of optic nerve resected during enucleation. METHODS: Case-control laboratory study on 22 orbits of 11 unpreserved, fresh-frozen human cadavers. Each cadaver underwent a conventional enucleation technique on one side and an otherwise identical technique on the contralateral side that included sub-Tenon injection of 2.5 ml normal saline in each oblique quadrant. Resected optic nerve lengths were measured and compared using Student t tests. RESULTS: The mean optic nerve length was 15.2 mm (range, 5.0-21.0 mm) in the sub-Tenon injection group and 11.3 mm (range, 5.0-19.0 mm) in control group (p = 0.015). CONCLUSIONS: Sub-Tenon injection during enucleation allows for significantly longer optic nerve resection lengths in unpreserved, fresh-frozen human cadavers. PMID- 24217482 TI - Novel technique to appose flaps using the BioGlue in the external dacryocystorhinostomy. AB - PURPOSE: To introduce the sutureless technique to appose flaps using the BioGlue composed of bovine serum albumin (45%) and glutaraldehyde (10%) in the external dacryocystorhinostomy (DCR). METHODS: The clinical chart was reviewed, retrospectively. The authors studied 31 case series of 30 patients who underwent the external DCR using the BioGlue in the step of apposing flaps. Instead of the suture technique, BioGlue was applied to appose flaps. Other steps were performed in the similar fashion to the conventional external DCR. And also, authors studied 31 case series of 30 patients who underwent the external DCR with conventional suture technique. RESULTS: Mean follow-up period is 12.5 months in study group and 12.6 months in control group. During mean follow up, 3 cases of membrane formation were observed, and patency of the anastomosis was kept well established in 28 cases (90%) in both groups. CONCLUSIONS: Sutureless apposition of flaps using the BioGlue can be an alternative method for the conventional suture technique in the external DCR. Also, it is easy and safe procedure to perform. PMID- 24217483 TI - Re: "Treatment of punctal occlusion using pigtail probe". PMID- 24217484 TI - Reply re: "Treatment of punctal occlusion using pigtail probe". PMID- 24217485 TI - Re: "Orbital development as a function of age in Indigenous North American skeletons". PMID- 24217486 TI - Reply re: "Orbital development as a function of age in Indigenous North American skeletons". PMID- 24217487 TI - Re: "Diagonal tarsal suture technique sine marginal sutures for closure of full thickness eyelid defects". PMID- 24217488 TI - Reply re: "Diagonal tarsal suture technique sine marginal sutures for closure of full-thickness eyelid defects". PMID- 24217489 TI - Re: "Cryptophthalmos: reconstructive techniques--expanded classification of congenital symblepharon variant". PMID- 24217490 TI - Reply re: "Cryptophthalmos: reconstructive techniques--expanded classification of congenital symblepharon variant". PMID- 24217491 TI - Bilateral squamous cell carcinoma of the lacrimal sac. AB - A 42-year-old man presented with right-sided epiphora, a fleshy lesion emanating from the right inferior punctum and a painless mass below the medial canthal tendon. Biopsy of the lacrimal sac mass disclosed papillary squamous cell carcinoma in situ. The patient underwent wide local excision with clear surgical margins and remained disease free until 28 months later when he returned with hemorrhagic epiphora of the OS and fullness overlying the left lacrimal sac. Biopsy confirmed papillary squamous cell carcinoma in situ. He underwent similar excision and has remained disease free for 6 months. To the best of the authors' knowledge, this is the first report of bilateral squamous cell carcinoma of the lacrimal sac. PMID- 24217492 TI - Motivation for living kidney donation in the developing world. PMID- 24217493 TI - [V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis]. PMID- 24217495 TI - A novel chiral yttrium complex with a tridentate linked amido-indenyl ligand for intramolecular hydroamination. AB - A new chiral silicon-linked tridentate amido-indenyl ligand was developed from indene and enantiopure 1,2-cyclohexanediamine. Its yttrium complex was synthesized, characterized and applied to efficiently catalyze the intramolecular hydroamination of non-activated olefins with up to 97% ee. PMID- 24217496 TI - To be or not to be metal-free: trends and advances in coupling chemistries. AB - Coupling reactions have been part of several extensive studies in order to develop innovative and greener protocols that can generate a wide range of compounds with applications in pharmaceuticals, agrochemicals and biologically active compounds. Metal-free couplings are an important and increasingly trendy field that has attracted a significant deal of interest in recent years, generating a lot of controversy on the issue of whether metal free is really free. Aside from focusing on such a controversial topic itself, this contribution aims to provide a brief introduction on coupling chemistry to point out the transition of this technology from metal-catalyzed to metal-free. This is followed by a range of key selected synthetically useful metal-free processes and a brief commentary on the current debate of whether metal-free reactions are really metal-free and the required experiments for a full understanding of a metal-free coupling process. PMID- 24217494 TI - Reverse translation of the rodent 5C-CPT reveals that the impaired attention of people with schizophrenia is similar to scopolamine-induced deficits in mice. AB - Attentional dysfunction in schizophrenia (SZ) is a core deficit that contributes to multiple cognitive deficits and the resulting functional disability. However, developing procognitive therapeutics for neuropsychiatric disorders have been limited by a 'translational gap'--a lack of cognitive paradigms having cross species translational validity and relevance. The present study was designed to perform an initial validation of the cross-species homology of the 5-choice Continuous Performance Test (5C-CPT) in healthy nonpsychiatric comparison subjects (NCS), SZ patients and mice under pharmacologic challenge. The 5C-CPT performance in SZ patients (n=20) was compared with age-matched NCS (n=23). The effects of the general muscarinic receptor antagonist scopolamine on mice (n=21) performing the 5C-CPT were also assessed. SZ subjects exhibited significantly impaired attention in the 5C-CPT, driven by reduced target detection over time and nonsignificantly increased impulsive responding. Similarly, scopolamine significantly impaired attention in mice, driven by reduced target detection and nonsignificantly increased impulsive responding. Scopolamine also negatively affected accuracy and speed of responding in mice, although these measures failed to differentiate SZ vs. NCS. Thus, mice treated with scopolamine exhibited similar impairments in vigilance as seen in SZ, although the differences between the behavioral profiles warrant further study. The availability of rodent and human versions of this paradigm provides an opportunity to: (1) investigate the neuroanatomic, neurochemical and genomic architecture of abnormalities in attention observed in clinical populations such as SZ; (2) develop and refine animal models of cognitive impairments; and (3) improve cross-species translational testing for the development of treatments for these impairments. PMID- 24217497 TI - Drinking patterns and associated problems in Brazil. AB - This paper describes patterns of alcohol consumption and associated problems in Brazil. Data came from a multicluster random sample of 2,346 Brazilians 18 years of age and older. The survey was conducted in 2005-2006 and had a response rate of 66.4%. About 35% of the men and 59% of the women did not drink in the past 12 months, while 39% of the men and 13% of the women consumed alcohol at least once a week. Further, 38% of the men and 17% of the women consumed 5 or more drinks "usually", and 40% of the men and 18% of the women reported binge drinking in the past 12 months. The prevalence of alcohol use disorders (DSM-4 abuse and/or dependence) was 19% among men and 4% among women. Although abstinence in Brazil is relatively high, binge drinking is frequent and, thus, alcohol problems and alcohol use disorders are also frequent. PMID- 24217498 TI - The drug scene in Mexico and the road ahead. AB - Mexico is a country affected by drugs in every aspect: it is a drug producing country of heroin, marihuana and methamphetamines, mainly for external markets but also for the growing internal demand; it is a transit country for cocaine that has found its way through the Central American and Mexican corridor on its way to external markets and for the internal supply. As a result of the increasing availability of substances and a favorable social environment, it has become a consuming country; drug experimentation use and dependence of illegal drugs, although still low, have increased. The abuse/dependence of legal substances such as alcohol and tobacco are the main substance abuse problems; only the abuse of pharmaceuticals remains low and relatively stable, mainly as a result of low availability for medical purposes and therefore limited scope for deviation. Social costs are considerable, as happens in other countries in the region, violence being the most prevailing characteristic of the drug scene, increasing from 2008 onwards. Within these important challenges for health and security, it is also true that significant, continuous efforts have been made by demand reduction programs at the national level since 1972 and adapted to the changing circumstances. This editorial seeks to tell the story of drug transitions in Mexico and the programs that have been implemented and discusses areas of opportunity for a new approach. PMID- 24217499 TI - [Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit]. AB - This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity. PMID- 24217500 TI - [Validation of the Training Addiction Scale (EAE) in master athletes]. AB - Measuring instruments for behavioral addictions tend to not be generalizable to other dependences. The aim is to carry out a process of adaptation of the General Addiction Scale (EAG) (Ramos, Sansebastian & Madoz, 2001), to assess exercise dependence. This test presents a self-administered one-dimensional character capable of measuring the degree of addiction of a subject to all kinds of new addictions, excluding illicit substances of abuse. The scale, after adjustment, was renamed as Training Addiction Scale (EAE). 401 athletes took part of which 82.29% are men and the whole sample indicated an age with M=45.78 and SD = 10.25 years. The confirmatory factor analysis has allowed discriminating a general factor and four subscales, with Cronbach's alpha for each of the sub-scales: Tolerance (alpha=.78), pleasure-relaxation (alpha=.77), Lack of Control (alpha=.77) and Abstinence-craving (alpha=.71). The indexes of asymmetry and curtosis have been near zero and <2.0. The items showed no overlap between the subscales. The model presented correct values for determining an acceptable goodness of fit of the original model and the results were: chi2 / df = 2.93, IFI = .96, CFI = .96, TLI = .93, SRMR = .039, RMSEA = .049. PMID- 24217501 TI - [Use of the condom and knowledge on HIV prevention among the injector's drugs in two Colombian cities]. AB - This research focuses on the use of the condom among injector drug users and the identification of their knowledge on HIV prevention that can inform interventions. A cross- sectional study was conducted, using respondent driven sampling (RDS); the sample was composed of 540 participants, of 18 years of age or older. The survey included counseling for HIV testing and the prevention of sexually transmitted diseases. In the multivariate analysis estimated a logistic regression model (explaining how to use the condom) multinomial with raw and adjusted OR. The proportion of drug-injector users who always used condoms during sexual intercourse with their partners was 21.1%. It was found that by adjusting the risk of not using a condom by ten inadequate assumptions on HIV prevention, factors that increase the risk are sharing the injection equipment (ORaj = 3. 19 [1. 29- 7.88]), having unsafe sex practices (ORaj = 3. 74 [1. 21-11. 58]) and not increasing the use of condom despite having knowledge of HIV (ORaj = 33. 59 [9. 19-122. 86]). The low use of condoms among intravenous drug users is associated with inadequate knowledge about HIV prevention. PMID- 24217502 TI - [Safe injection rooms and police crackdowns in areas with heavy drug dealing. Evaluation by counting discarded syringes collected from the public space]. AB - The evolution of drug injection in public places is analysed using as indicator the number of syringes collected from public spaces, evaluating as well the influence of public health harm reduction interventions and of police actions, with a before and after quasi experimental study. Monthly syringe counts on the semester before and after each intervention were compared both in the involved district and in the city as a whole, using the U and z tests with a 95% confidence level. The average number of collected syringes drops from 13.132 in 2004 to 3.190 in 2012. Comparing indicators before and after health and police interventions, the opening of a facility with a supervised drug consumption room in the inner city was associated with a huge reduction in the number of abandoned syringes in the city, while its number did not rise in the district where the facility was located. The subsequent opening of another drug consumption room did not have a significant impact in collected syringes in the area. Some police interventions in 2005-2006 and 2011 had a significant impact in the indicators of the involved districts, while others did not. Harm reduction programs might have a favourable impact on drug injection in public spaces and related syringe presence. Some police interventions appear to have an impact while others do not or just have a modest local and temporary effect. PMID- 24217503 TI - [Spanish adaptation of the Substance Dependence Severity Scale: preliminar results]. AB - The Substance Dependence Severity Scale -SDSS- is one of the few scales that assesses substance dependence and abuse according DSM criteria in dimensional terms. Several studies have provided evidence of psychometric validity and reliability in its English version, but there is no Spanish version available. The aim of this work was to describe the adaptation process of the English version of the SDSS into Spanish, and provide preliminary results on its reliability and validity evidence. Participants were 146 patients (79.6% male), consumers of alcohol, cocaine, heroin and cannabis admitted to treatment in the Drug Abuse Centre Services of Huelva. Besides the SDSS, the EUROPASI and the Health Related Quality of Life for Drug Abusers test -HRQOLDA- were also administered. The Substance Dependence Severity Scale -SDSS- has shown adequate psychometric properties in terms of the rates of discrimination and internal consistency (alpha=0.881 for alcohol; alpha=0.814 for cocaine; alpha=0.531 for cannabis; alpha=0.785 for heroin). However, the scale assessing abuse showed poorer results. Concerning the validity evidence, the evidence based on internal structure showed a unidimensional structure. Furthermore, the evidence based from the relationships with other variables empirically support the theoretical relationships postulated. Preliminary results support the use of the Substance Dependence Severity Scale. The severity scale, which evaluates abuse criteria, needs further empirical evidence to assess its utility. Therefore, its current version is not recommended for use. PMID- 24217504 TI - [Differential association between the regional metabolism of the prefrontal cortex and limbic structures, and the time of abstinence in substance dependent individuals]. AB - Despite the existence of numerous neuroimaging studies demonstrating significant brain functional alterations in substance users, only a few studies have tried to analyze the association between the duration of abstinence and brain metabolism within substance users. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F fluordeoxyglucose Positron Emission Tomography (FDGPET) and duration of drug abstinence in a sample of 49 abstinent polysubstance users. PET images were pre processed and analyzed using SPM5 and SPSS 15. After image pre-processing, the level of glucose uptake in a pre-established set of regions of interest was extracted and bivariate correlations between this and the duration of abstinence of the participants were conducted. Results showed a negative correlation between duration of abstinence and the amygdale and the hippocampus bilaterally and a positive correlation between duration of abstinence and the left inferior frontal operculum. The associations found suggest different involvement of these structures in maintaining abstinence and emphasize the need to work on stress regulation, craving and behaviour control even after significant periods of abstinence. PMID- 24217505 TI - Changing pattern of alcohol consumption in Russia. PMID- 24217506 TI - Methadone dosing based on testosterone-to-creatinine urine ratio. PMID- 24217507 TI - Erb-041, an estrogen receptor-beta agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. AB - Estrogen receptors (ER), including ER-alpha and ER-beta, are known to regulate multiple biologic responses in various cell types. The expression of ER-beta is lost in various cancers. ER-beta agonists were shown to modulate inflammation, cancer cell proliferation, and differentiation. Here, we investigated the cancer chemopreventive properties of Erb-041, an ER-beta agonist, using a model of UVB induced photocarcinogenesis in SKH-1 mice. Erb-041 significantly reduced UVB induced carcinogenesis. Tumor numbers and volume were reduced by 60% and 84%, respectively, in the Erb-041-treated group as compared with UVB (alone) control. This inhibition in tumorigenesis was accompanied by the decrease in proliferating cell nuclear antigen (PCNA), cyclin D1, VEGF, and CD31, and an increase in apoptosis. The lost ER-beta expression in squamous cell carcinomas (SCC) was significantly recovered by Erb-041 treatment. In addition, the UVB-induced inflammatory responses were remarkably reduced. Myeloperoxidase activity, levels of cytokines (interleukin (IL)-1beta, IL-6, and IL-10), and expression of p-ERK (extracellular signal-regulated kinase) 1/2, p-p38, p-IkappaB, iNOS, COX-2, and nuclear NF-kappaBp65 were diminished. The number of tumor-associated inflammatory cells (GR-1(+)/CD11b(+) and F4/80(+)) was also decreased. Tumors excised from Erb 041-treated animal were less invasive and showed reduced epithelial-mesenchymal transition (EMT). The enhanced expression of E-cadherin with the concomitantly reduced expression of N-cadherin, Snail, Slug, and Twist characterized these lesions. The WNT/beta-catenin signaling pathway, which underlies pathogenesis of skin cancer, was found to be downregulated by Erb-041 treatment. Similar but not identical changes in proliferation and EMT regulatory proteins were noticed following treatment of tumor cells with a WNT signaling inhibitor XAV939. Our results show that Erb-041 is a potent skin cancer chemopreventive agent that acts by dampening the WNT/beta-catenin signaling pathway. PMID- 24217508 TI - Equilibrium selectivity alone does not create K+-selective ion conduction in K+ channels. AB - Potassium (K(+)) channels are selective for K(+) over Na(+) ions during their transport across membranes. We and others have previously shown that tetrameric K(+) channels are primarily occupied by K(+) ions in their selectivity filters under physiological conditions, demonstrating the channel's intrinsic equilibrium preference for K(+) ions. Based on this observation, we hypothesize that the preference for K(+) ions over Na(+) ions in the filter determines its selectivity during ion conduction. Here, we ask whether non-selective cation channels, which share an overall structure and similar individual ion-binding sites with K(+) channels, have an ion preference at equilibrium. The variants of the non selective Bacillus cereus NaK cation channel we examine are all selective for K(+) over Na(+) ions at equilibrium. Thus, the detailed architecture of the K(+) channel selectivity filter, and not only its equilibrium ion preference, is fundamental to the generation of selectivity during ion conduction. PMID- 24217510 TI - Alzheimer disease therapy--moving from amyloid-beta to tau. AB - Disease-modifying treatments for Alzheimer disease (AD) have focused mainly on reducing levels of amyloid-beta (Abeta) in the brain. Some compounds have achieved this goal, but none has produced clinically meaningful results. Several methodological issues relating to clinical trials of these agents might explain this failure; an additional consideration is that the amyloid cascade hypothesis- which places amyloid plaques at the heart of AD pathogenesis--does not fully integrate a large body of data relevant to the emergence of clinical AD. Importantly, amyloid deposition is not strongly correlated with cognition in multivariate analyses, unlike hyperphosphorylated tau, neurofibrillary tangles, and synaptic and neuronal loss, which are closely associated with memory deficits. Targeting tau pathology, therefore, might be more clinically effective than Abeta-directed therapies. Furthermore, numerous immunization studies in animal models indicate that reduction of intracellular levels of tau and phosphorylated tau is possible, and is associated with improved cognitive performance. Several tau-related vaccines are in advanced preclinical stages and will soon enter clinical trials. In this article, we present a critical analysis of the failure of Abeta-directed therapies, discuss limitations of the amyloid cascade hypothesis, and suggest the potential value of tau-targeted therapy for AD. PMID- 24217509 TI - Brain repair after stroke--a novel neurological model. AB - Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment- from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke. PMID- 24217512 TI - Multiple sclerosis: CCSVI deconstructed and discarded. PMID- 24217518 TI - Advances in peripheral nerve regeneration. AB - Rodent models of nerve injury have increased our understanding of peripheral nerve regeneration, but clinical applications have been scarce, partly because such models do not adequately recapitulate the situation in humans. In human injuries, axons are often required to extend over much longer distances than in mice, and injury leaves distal nerve fibres and target tissues without axonal contact for extended amounts of time. Distal Schwann cells undergo atrophy owing to the lack of contact with proximal neurons, which results in reduced expression of neurotrophic growth factors, changes in the extracellular matrix and loss of Schwann cell basal lamina, all of which hamper axonal extension. Furthermore, atrophy and denervation-related changes in target tissues make good functional recovery difficult to achieve even when axons regenerate all the way to the target tissue. To improve functional outcomes in humans, strategies to increase the speed of axonal growth, maintain Schwann cells in a healthy, repair-capable state and keep target tissues receptive to reinnervation are needed. Use of rodent models of chronic denervation will facilitate our understanding of the molecular mechanisms of peripheral nerve regeneration and create the potential to test therapeutic advances. PMID- 24217519 TI - Alzheimer disease: Sleep alleviates AD-related neuropathological processes. PMID- 24217516 TI - Pathophysiology of somatosensory abnormalities in Parkinson disease. AB - Changes in sensory function that have been described in patients with Parkinson disease (PD) can be either 'pure' disorders of conscious perception such as elevations in sensory threshold, or disorders of sensorimotor integration, in which the interaction between sensory input and motor output is altered. In this article, we review the extensive evidence for disrupted tactile, nociceptive, thermal and proprioceptive sensations in PD, as well as the influences exerted on these sensations by dopaminergic therapy and deep brain stimulation. We argue that abnormal spatial and temporal processing of sensory information produces incorrect signals for the preparation and execution of voluntary movement. Sensory deficits are likely to be a consequence of the dopaminergic denervation of the basal ganglia that is the hallmark of PD. A possible mechanism to account for somatosensory deficits is one in which disease-related dopaminergic denervation leads to a loss of response specificity, resulting in transmission of noisier and less-differentiated information to cortical regions. Changes in pain perception might have a different explanation, possibly involving disease-related effects outside the basal ganglia, including involvement of peripheral pain receptors, as well as structures such as the periaqueductal grey matter and non dopaminergic neurotransmitter systems. PMID- 24217524 TI - Effects of sugarcane waste-products on Cd and Zn fractionation and their uptake by sugarcane (Saccharum officinarum L.). AB - The effects of three sugarcane waste-products from an ethanol production plant on the fractionation of Cd and Zn in high Cd and Zn contaminated soil and metal accumulation in sugarcane (Saccharum officinarum L.) were studied, using the BCR sequential extraction and aqua regia extraction procedures. A pot experiment was performed for 4 months with four treatments: no-amendments (control), boiler ash (3% w/w), filter cake (3% w/w) and a combination of boiler ash and vinasse (1.5% + 1.5%, w/w). The results showed that all treatments reduced the most bioavailable concentrations of Cd and Zn (BCR1 + 2) in soils (4.0-9.6% and 5.5 6.3%, respectively) and metal uptake (MUg) in the aboveground part of the sugarcane (up to 62% and 54% for Cd and Zn, respectively) as compared to the control. No visual symptoms of metal toxicity and no positive effect on the biomass production of sugarcane were observed. Both Cd and Zn were accumulated mainly in the underground parts of the sugarcane (root > shoot >= underground sett > leaf; and root > underground sett > shoot > leaf, respectively) and the translocation factors were below 1, indicating low metal uptake. The results suggested that even though sugarcane waste-products insignificantly promote sugarcane growth, they can be used in agriculture due to the low metal accumulation in sugarcane and the reduction in metal bioavailability in the soil. PMID- 24217521 TI - Amyotrophic lateral sclerosis--a model of corticofugal axonal spread. AB - The pathological process underlying amyotrophic lateral sclerosis (ALS) is associated with the formation of cytoplasmic inclusions consisting mainly of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43), which plays an essential part in the pathogenesis of ALS. Preliminary evidence indicates that neuronal involvement progresses at different rates, but in a similar sequence, in different patients with ALS. This observation supports the emerging concept of prion-like propagation of abnormal proteins in noninfectious neurodegenerative diseases. Although the distance between involved regions is often considerable, the affected neurons are connected by axonal projections, indicating that physical contacts between nerve cells along axons are important for dissemination of ALS pathology. This article posits that the trajectory of the spreading pattern is consistent with the induction and dissemination of pTDP 43 pathology chiefly from cortical neuronal projections, via axonal transport, through synaptic contacts to the spinal cord and other regions of the brain. PMID- 24217525 TI - Palliative care = hope. PMID- 24217526 TI - Reply: To PMID 23147806. PMID- 24217527 TI - [Genetic risk factors for vasculitis]. AB - Among the vasculitides, genome-wide association studies (GWAS) have so far been performed for Behcet's disease, Kawasaki disease, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These studies delivered valuable information with respect to the pathogenesis and therapeutic targets: Apart from HLA-B51 and HLA-A26, distinct polymorphisms in cytokine (IL-10) or cytokine receptor (IL-12R/IL-23R) genes, transcription factors (STAT4) and genes encoding for proteins involved in antigen presentation (ERAP-1) have been identified as risk factors for Behcet's disease. The results of two GWAS performed for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis GPA and MPA in Europe and the USA confirmed that the HLA-DP locus is the most relevant risk factor for GPA. Furthermore, the European GWAS confirmed SERPINA-1, a deficiency allele of the alpha-1-antitrypsin gene, as a genetic risk factor in GPA and identified a polymorphism in the proteinase 3 gene (PR3), one of the target antigens of ANCA, as a risk factor for GPA and PR3-ANCA-associated vasculitis. PMID- 24217528 TI - [Genetic risk profile of sarcoidosis]. AB - Sarcoidosis is a multifactorial and polygenic disorder. The current knowledge of its genetic basis will be presented and functional consequences of the genetic variants that influence the immunopathogenesis of this disorder will be depicted. In the near future it is expected that this knowledge will yield clinically applicable genetic risk profiles. PMID- 24217529 TI - [Current management of renal artery stenosis]. AB - Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (ischemic kidney disease) or rarely pulmonary flush edema may occur. Renal artery stenosis may be treated by revascularization, using either percutaneous (balloon angioplasty, stenting) or less common open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management alone (except for fibromuscular disease). Furthermore, endovascular procedures are associated with substantial risks. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Careful patient selection is essential to maximize the potential benefit. PMID- 24217530 TI - [Current treatment of tachycardia]. AB - Tachycardias including atrial fibrillation often require hospitalisation. A diagnostic algorithm from the surface ECG allows discrimination between supraventricular and ventricular tachycardias. For acute treatment, only a few antiarrhythmic drugs such as adenosine, ajmaline and amiodarone, and in case of hemodynamic instability electrocardioversion are required. For long-term treatment catheter ablation is the option of choice for almost all patients with supraventricular tachycardias, atrial flutter, idiopathic ventricular tachycardias and for many patients with symptomatic atrial fibrillation. Chronic antiarrhythmic drug therapy is less often used. In patients with ventricular tachyarrhythmias in the setting of severe structural heart disease, risk stratification must be performed and ICD therapy is often indicated. Anticoagulant therapy according to risk score analysis is often indicated in patients with atrial fibrillation. PMID- 24217531 TI - Inverted segment size and the presence of recombination hot spot clusters matter in sperm segregation analysis. PMID- 24217532 TI - A graphene-MnO2 framework as a new generation of three-dimensional oxygen evolution promoter. AB - A three-dimensional framework promoter of graphene-MnO2 was fabricated to enhance the catalytic properties of NiCo2O4. The as-resultant graphene-MnO2-NiCo2O4 hybrid material features a number of remarkable structural properties such as well-developed pores, 3D conductive networks and strong coupling synergistic effects, rendering it an outstanding catalyst for electrocatalytic oxygen evolution. PMID- 24217533 TI - Assessing therapy response of secreting pineal germ cell tumor on simultaneous 18F-choline PET/MRI. AB - An 18-year-old man presented with 6 weeks' history of diplopia, early morning headaches, and blurred vision; on ophthalmologic examination, Parinaud syndrome was revealed. Brain MRI scan showed a calcified pineal mass. Brain simultaneous PET/MRI with 18F-choline showed an avid enhancing mass occupying the pineal region with restricted diffusion. A second examination after chemotherapy demonstrated reduction in both size and radiotracer activity of the mass. Our study emphasizes the potential of simultaneous 18F-choline PET/MRI being a useful tool for contribution in the diagnosis and treatment assessment in a convenient way with minimal radiation exposure and reduced throughput patient time. PMID- 24217534 TI - Diagnosis of complex renal cystic masses and solid renal lesions using PET imaging: comparison of 11C-acetate and 18F-FDG PET imaging. AB - PURPOSE: The study aims to assess the usefulness of PET with C-acetate and F-FDG to differentiate renal cell carcinoma (RCC) from complicated renal cysts. METHODS: Thirty-one patients were enrolled, 14 patients with complicated renal cysts (12 with Bosniak III and 2 with Bosniak IV) and 17 patients with 19 solid renal tumors. The patients underwent both C-acetate PET and FDG PET. Nephrectomy or partial nephrectomy was performed after the PET scans. RESULTS: In 29 patients, 32 renal lesions were diagnosed as RCC. Twenty-three of the 32 RCCs (72%) had positive C-acetate PET findings, whereas only 7 FDG PET studies were positive (22%). Considering the relationship between tumor size measured by macroscopic appearance of resected tumors and PET results, 22 of 25 (88%) tumors more than 1.5 cm showed positive C-acetate PET findings. In 12 patients with Bosniak III renal cysts, 10 renal lesions were diagnosed as RCC. In this subgroup, 5 of the 10 RCCs (50%) had positive C-acetate PET findings, whereas 2 RCCs (20%) had positive FDG PET findings. None of the cases with benign findings had positive C-acetate PET or FDG PET scans. CONCLUSIONS: C-acetate PET demonstrates a pronounced increase in tracer uptake in RCC, especially in renal tumors more than 1.5 cm, and displays a higher sensitivity than FDG PET. These preliminary data show that C-acetate may be a useful PET tracer to exclude RCC in complex renal cysts. PMID- 24217535 TI - Hepatorenal cutaneous syndrome demonstrated by 99mTc macro aggregated albumin whole-body scintigraphy. AB - Hepatopulmonary syndrome, also known as hepatorenal syndrome, is a triad of liver disease, impaired oxygenation, and intrapulmonary vascular abnormalities. Forty seven percent of patients with end-stage liver disease may have hepatopulmonary syndrome, an independent predictor of poor prognosis. Gross dilatation of pulmonary precapillary and capillary vessels, as well as an absolute increase in the number of dilated vessels, is the classic pathological description. We report a young man with cirrhosis demonstrating extrapulmonary shunting of 99mTc-MAA to kidneys with extensive peripheral arteriovenous (cutaneous) vasodilation, which we prefer to name as the "mosaic sign" in the absence of spider nevi or erythema. PMID- 24217536 TI - Different lesions revealed by 18F-FDG PET/CT and 18F-NaF PET/CT in patients with multiple myeloma. AB - We present different findings on 18F-FDG PET/CT and 18F-NaF PET/CT images in 2 patients with multiple myeloma. In 1 case, 18F-FDG PET/CT showed intense uptake in the lesions in the axial skeleton where 18F-NaF PET/CT seemed normal. In addition, a sternal lesion showed FDG uptake only in the center but NaF uptake only in the periphery. In another patient, intense NaF accumulation in a dorsal vertebra was noted, but the corresponding FDG uptake was unimpressive. The role of these 2 radioactive tracers in the management of multiple myeloma continues to be defined. PMID- 24217537 TI - Prospective multicenter study of bone scintigraphy in consecutive patients with newly diagnosed prostate cancer. AB - BACKGROUND: International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy (BS) in low-risk prostate cancer (PCa). These recommendations are based on retrospective investigations only. In addition, BS has most often been reported as a definitive investigation with no room for equivocal cases. OBJECTIVE: The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa. DESIGN, SETTING, AND PARTICIPANTS: Over a period of 1.5 years in 2008 to 2009, consecutive patients with newly diagnosed PCa were enrolled in a noninterventional, multicenter, observational study. All patients had a whole body, planar BS. Clinical history and clinical, pathological, and biochemical data were obtained from electronic patient files and questionnaires. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bone scintigraphy was classified into 4 categories as nonmalignant, equivocal, likely malignant, or multiple metastasis. The primary end point was final imaging, which was a composite end point of BS and additional CT and MRI investigations. RESULTS AND LIMITATIONS: A total of 635 eligible patients were recruited. Their median prostate-specific antigen (PSA) was 15 ng/mL, median Gleason was 7, and 80% of patients had local disease (T1 or T2). The proportion of nonmalignant BS was 61%, equivocal scans 26%, and likely or definitive metastasis 13%. A total of 154 patients had additional CT or MRI investigations. The final imaging diagnosis showed a prevalence of bone metastases in 87 (13.7%) of 635 patients. No bone metastases were observed in (1) patients with PSA of less than 10 ng/mL, independently of the clinical Tstage and Gleason score (n = 212) and (2) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 (n = 97). Approximately 50% of the patients enrolled in this study met these criteria. CONCLUSION: This is the first prospective trial to demonstrate that BS can be avoided in patients with low-risk PCa. PMID- 24217538 TI - Diffuse FDG uptake of the bilateral atrial walls in a patient with atrial fibrillation. AB - A 59-year-old man, who had a 3-year history of paroxysmal atrial fibrillation, was referred to our hospital because of palpitation for 12 hours. Atrial fibrillation was confirmed by ECG. F-FDG PET/CT scan was performed showing diffuse FDG uptake of the bilateral atrial walls. Enhanced chest CT showed that the bilateral atria and ventricles were normal. This case highlights that atrial fibrillation should be included in the differential diagnosis of abnormal atrial FDG accumulation along with tumor and inflammatory processes. PMID- 24217539 TI - Dual tracer functional imaging of gastroenteropancreatic neuroendocrine tumors using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT: competitive or complimentary? AB - OBJECTIVE: This study aimed to compare the diagnostic performance of Ga-DOTANOC PET/CT with F-FDG PET/CT in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). PATIENTS AND METHODS: Data of 51 patients with definite histological diagnosis of GEP-NET who underwent both Ga-DOTA-NOC PET-CT and F-FDG PET-CT within a span of 15 days were selected for this retrospective analysis. Sensitivity, specificity, and predictive values were calculated for Ga DOTA-NOC PET-CT and F-FDG PET-CT, and results were compared both on patientwise and regionwise analysis. RESULTS: Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT on patientwise analysis (P < 0.0001). On regionwise analysis, Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT only for lymph node metastases (P < 0.003). Although Ga-DOTA-NOC PET-CT detected more liver and skeletal lesions compared with F-FDG PET-CT, the difference was not statistically significant. In addition, the results of combined imaging helped in selecting candidates who would undergo the appropriate mode of treatment, whether octreotide therapy or conventional chemotherapy CONCLUSIONS: Ga-DOTA-NOC PET-CT seems to be superior to F-FDG PET-CT for imaging GEP-NETs. However, their role seems to be complementary because combination of Ga-DOTA-NOC PET-CT and F-FDG PET-CT in such patients helps demonstrate the total disease burden and segregate them to proper therapeutic groups. PMID- 24217540 TI - Organized urachal abscess mimicking urachal carcinoma on FDG PET/CT. AB - Urachal inflammation is rarely seen in adults. Two patients with suspected abdominal tumor underwent FDG PET/CT. One patient showed an irregular hypermetabolic mass anterosuperior to the bladder. The other patient showed a thick-walled cystic mass with strong FDG uptake extending from the bladder dome to the anterior abdominal wall. Urachal carcinomas were suspected based on imaging findings. Both patients underwent complete resection of the masses. However, both masses were organized urachal abscesses confirmed by pathological examination. These two cases highlight that differentiation between organized urachal abscess and carcinoma is difficult on the basis of imaging. PMID- 24217541 TI - Easy interpretation of heterotopic ossification demonstrated on bone SPECT/CT. AB - A 29-year-old male patient suffered from paraplegia 6 months after brain injury. Heterotopic ossification was diagnosed based on clinical characteristics such as decreased range of motion at the bilateral hips without infective signs. A planar bone scintigraphy using Tc-MDP showed intensive radiotracer accumulation in the proximal portion of the bilateral femurs and the right acetabulum. The SPECT/CT images showed increased radiotracer accumulation in the adjacent soft tissues of the bilateral hips but not in the bone. The conservative treatment rather than surgical intervention was given according to the findings in bone SPECT/CT images. PMID- 24217542 TI - 18F-FDG PET/CT imaging features of Rosai Dorfman disease: a rare cause of massive generalized lymphadenopathy. AB - Rosai Dorfman disease (RDD) or sinus histiocytosis is a rare non-neoplastic idiopathic disease characterized by massive lymphadenopathy in young adults. Extranodal involvement is seen in 25%-43% cases. RDD is usually self-remitting. However, it mimics lymphoproliferatve disorders clinically as well as on imaging. We present the F-FDG PET/CT findings in a 46-year-old female patient with nodal RDD. PMID- 24217543 TI - Lymphoma as a second malignancy in a patient with neuroendocrine tumor: mimicking dedifferentiation on dual-tracer PET/CT with 68Ga-DOTANOC and 18F-FDG. AB - Neuroendocrine tumors (NETs) are rare tumors which express somatostatin receptors (SSTRs). We here present a case of a 50-year-old female patient with metastatic bronchial carcinoid. She underwent 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT which suggested a diagnosis of poorly differentiated NET. Biopsy of the lesion, however, revealed a second malignancy in the form of diffuse large B-cell lymphoma. Thus, very rarely, other primary tumors can mimic NETs on dual-tracer PET/CT, and biopsy is advised in doubtful cases. PMID- 24217544 TI - Myocardial uptake of 99mTc-HDP and reduced perfusion on CT in subacute myocardial infarction. AB - A 65-year-old man with known bone metastases from prostate cancer and no cardiac history attended for a restaging bone scan (BS). Diffuse increased Tc-HDP activity in the heart was noted, new since a BS 3 months earlier. A restaging contrast-enhanced CT scan on the same day showed reduced myocardial perfusion in the anterior, apical, and septal walls. On direct questioning, he described an episode of severe exertional chest pain the day before. Myocardial infarction was confirmed and treated with primary percutaneous coronary intervention. New cardiac uptake on BS, raising the possibility of myocardial infarction, is a red alert for clinicians. PMID- 24217545 TI - Peptide receptor radionuclide therapy with (177)Lu DOTATATE in a case of recurrent carotid body paraganglioma with spinal metastases. AB - Paragangliomas are rare benign neuroendocrine tumors, and 80% of all paragangliomas are either carotid body tumors or glomus jugulare tumors. We present a case of recurrent unresectable carotid body paraganglioma with nodal and T7 vertebral metastases in a 30-year-old man 6 years postsurgery detected with Ga DOTANOC PET/CT and was administered with peptide receptor radionuclide therapy using Lu DOTATATE. After 5 cycles of Lu DOTATATE (total cumulative activity of 750 mCi [27 GBq]), significant response at the primary site on Ga DOTANOC PET/CT and complete disappearance of nodal and T7 vertebral metastases were noted. PMID- 24217546 TI - First experience with image-guided resection of paraganglioma. AB - A 32-year-old male patient showed 2 focal uptakes of I-MIBG next to the left renal vein in a diagnostic scan, corresponding to paragangliomas. An operation was indicated, and to guide resection during surgery we used the freehand SPECT system. In the operating room, using freehand SPECT, both lesions were found. The system was of additional value in planning the operative access to the region of interest and in determining the depth of 1 lesion for precise and more rapid extirpation. Furthermore, it confirmed no residues in the operating field after resection of the tumors. PMID- 24217547 TI - Pretreatment (18)F-FDG PET/CT in whole-body total lesion glycolysis to predict survival in patients with pharyngeal cancer treated with definitive radiotherapy. AB - PURPOSE: The objective of this study was to examine the predictive role of pretreatment total lesion glycolysis (TLG) of the whole-body and primary tumors in patients with pharyngeal cancer (PC) treated with definitive radiotherapy. METHODS: The retrospective analysis examined 74 PC patients treated with radiotherapy. All patients received pretreatment with F-FDG PET/CT. Several autosegmentation methods were used to determine the PET/CT-based metabolic tumor volume (MTV), TLG of the primary tumor, and whole-body TLG (TLGw) for each patient. Overall survival (OS), disease-free survival (DFS), and primary relapse free survival (PRFS) were examined according to the cutoffs of the median values for MTV, TLG, and gross tumor volume of the primary tumor. Independent prognosticators were identified using Cox regression analysis. RESULTS: After a median follow-up of 33 months, 42 patients remained disease-free, and 32 patients experienced cancer recurrence. Multivariate analysis of the OS and DFS showed that the application of 40% of the maximal uptake of whole body TLG(TLGw40%) was the only predictor of OS or DFS. Patients who had tumors with TLGw40% greater than 92 g had significantly lower 3-year OS and DFS compared with patients who had smaller TLGw. The independent predictors for PRFS were MTV greater than the SUVmax of 2.5 (MTV2.5). CONCLUSIONS: For PC patients treated with definitive radiotherapy, pretreatment with TLGw40% achieved the optimal predictive value for OS and DFS, and MTV2.5 was a prognosticator for PRFS. PMID- 24217548 TI - MRI and FDG PET/CT findings of malignant fibrous histiocytoma of the prostate. AB - Malignant fibrous histiocytoma primarily arising from the prostate is extremely rare. A 43-year-old man presented with dysuria for 12 months. Serum prostate specific antigen level was normal. T2-weighted MR images showed a well circumscribed tumor with inhomogeneous intensity in the prostate. The patient underwent transurethral resection of the prostate. Prostate malignant fibrous histiocytoma was histopathologically confirmed. FDG PET/CT was performed showing extremely high FDG uptake of the tumor with SUVmax of 46.8. PMID- 24217549 TI - Focal and diffuse FDG uptake patterns of endotracheal lymphoma. AB - Endotracheal infiltration by lymphoma is uncommon. We present 2 cases of endotracheal infiltration by non-Hodgkin lymphoma. One case had a solitary lesion in the middle trachea. Bronchoscopic biopsy of the lesion revealed diffuse large B-cell lymphoma. The tumor showed focal FDG uptake with SUVmax of 15. The other case had diffuse endotracheal lesions. Bronchoscopic biopsy revealed diffuse submucosal infiltration by natural killer/T-cell lymphoma. The thickened trachea showed diffuse FDG uptake with SUVmax of 8.4. These 2 cases indicate lymphoma should be included in the differential diagnosis of focal or diffuse endotracheal FDG accumulation. PMID- 24217550 TI - Benign cystic mesothelioma: false-positive iodine accumulation in a patient with oncocytic follicular thyroid carcinoma. AB - Whole-body (131I) scintigraphy (WBS) is used to detect residual or metastatic tissue during treatment of differentiated thyroid carcinoma in combination with thyroglobulin (Tg) and ultrasonography of the neck. It is a highly sensitive method, but there is a high rate of false positives. We report the case of a 52 year-old woman with false-positive iodine accumulation in a benign cystic mesothelioma discovered during treatment for a oncocytic follicular thyroid carcinoma (stage pT2 pNx Mx). This lesion was detected by WBS and confirmed by surgery and histopathologic analysis. PMID- 24217551 TI - Adrenal masses of varied etiology: anatomical and molecular imaging features on PET-CT. AB - A wide spectrum of benign and malignant diseases can present as an adrenal mass. Combined PET-CT is useful for evaluation of adrenocortical and adrenomedullary masses. F-FDG has been extensively used as PET radiotracer for this purpose. F FDOPA PET, Ga-DOTA peptide (Ga-DOTANOC/TATE) PET, and C-HED PET have also been used for imaging of adrenal medullary lesions, whereas C-MTO PET has been used for adrenocortical imaging. We provide a review of imaging characteristics of adrenal gland pathologies on PET-CT using different tracers. PMID- 24217554 TI - Screen-and-treat approach to cervical cancer prevention using visual inspection with acetic acid and cryotherapy: experiences, perceptions, and beliefs from demonstration projects in Peru, Uganda, and Vietnam. AB - Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success. PMID- 24217555 TI - Advancing cervical cancer prevention in India: implementation science priorities. AB - Cervical cancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large-scale, organized cervical cancer prevention programs in the country. We conducted a review of the cervical cancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervical cancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervical cancer prevention efforts have the desired impact and are cost-effective. Specifically, implementation science research is needed to understand individual- and community-level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervical cancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervical cancer prevention and control result in the greatest impact. PMID- 24217557 TI - Recent advances in amino acid N-carboxyanhydrides and synthetic polypeptides: chemistry, self-assembly and biological applications. AB - Polypeptides are fascinating materials with unique properties for various biological materials. We highlight here recent advances in amino acid N carboxyanhydrides (NCAs) and synthetic polypeptides from the aspects of chemistry, self-assembly and biological applications. New synthetic methodologies, mechanistic studies and optimization of polymerization conditions for the preparation of well-defined novel polypeptides are comprehensively reviewed and evaluated. Functional polypeptides, mostly prepared from novel NCA monomers, with ultra-stable helical conformation, stimuli-sensitive properties, or glycoprotein mimetics are summarized. We also highlight a number of interesting self-assembled structures of polypeptides in solid state and solution, with particular emphasis on those structures other than amphiphilic self-assembly. The biological applications of polypeptides in drug and gene delivery are also reviewed. Future directions and perspectives are discussed in the conclusion. PMID- 24217556 TI - Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity. AB - Gene signatures of drug-induced toxicity are of broad interest, but they are often identified from small-scale, single-time point experiments, and are therefore of limited applicability. To address this issue, we performed multivariate analysis of gene expression, cell-based assays, and histopathological data in the TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system) database. Data mining highlights four genes-EGR1, ATF3, GDF15 and FGF21-that are induced 2 h after drug administration in human and rat primary hepatocytes poised to eventually undergo cytotoxicity-induced cell death. Modelling and simulation reveals that these early stress-response genes form a functional network with evolutionarily conserved structure and intrinsic dynamics. This is underlined by the fact that early induction of this network in vivo predicts drug-induced liver and kidney pathology with high accuracy. Our findings demonstrate the value of early gene-expression signatures in predicting and understanding compound-induced toxicity. The identified network can empower first-line tests that reduce animal use and costs of safety evaluation. PMID- 24217558 TI - Antitumor activity of cucumarioside A2-2. AB - BACKGROUND: The cytotoxic activity of sea cucumber glycosides against different types of cells and cell lines, including human tumor cell lines, has been studied for many years. However, the molecular mechanism(s) of the antitumor action of triterpene glycosides on cancer cells remain unclear. This article reports a continuation of investigations of triterpene glycoside cucumarioside A2-2 isolated from the Far-Eastern sea cucumber Cucumaria japonica. It describes a study of glycoside anticancer activity in vivo and glycoside interaction with mouse Ehrlich carcinoma cells in vitro. METHODS: The cytotoxicity of cucumarioside A2-2 and its effect on apoptosis, the cell cycle, DNA biosynthesis and p53 activity, and glycoside anticancer action against Ehrlich carcinoma cells were studied. RESULTS: Cucumarioside A2-2 influences tumor cell viability at micromolar concentrations. The EC50 for glycoside estimated by nonspecific esterase assay and MTT assay was 2.1 and 2.7 MUM, respectively. Cucumarioside A2 2 at a subcytotoxic range of concentrations exhibits a cytostatic effect by blocking cell proliferation and DNA biosynthesis in the S phase. It may induce apoptosis in tumor cells in a caspase-dependent way, bypassing the activation of the p53-dependent segment. CONCLUSION: The anticancer and proapoptotic properties of cucumarioside A2-2 may be due to direct interaction of the glycoside with tumor cells. The in vivo anticancer effect of cucumarioside A2-2 may be associated with the ability of the drug to arrest the cell cycle in the synthetic phase and induce programmed tumor cell death. PMID- 24217559 TI - Left and right ventricular structure and function in subclinical hypothyroidism: the effects of one-year levothyroxine treatment. AB - BACKGROUND: The aim of this study was to investigate left ventricular (LV) and right ventricular (RV) structure, function, and mechanics in patients with subclinical hypothyroidism (SHT), and to evaluate the effect of a 1-year levothyroxine treatment. MATERIAL AND METHODS: We compared 45 untreated women with subclinical hypothyroidism and 35 healthy control women matched by age. All the subjects underwent laboratory analyses, which included a thyroid hormone levels (free T3, free T4, and TSH) test, and a complete 2-dimensional echocardiographic study. All the SHT patients received levothyroxine therapy and were followed for a year after euthyroid state was achieved. RESULTS: The LV mass index in the SHT participants before and after replacement therapy was significantly higher than in controls. In the SHT patients before the treatment, LV diastolic function and global function estimated by the Tei index were significantly impaired, whereas the LV systolic function was decreased. The results show that LV mechanics was significantly impaired in the SHT patients at baseline. Additionally, the SHT participants before levothyroxine substitution had increased RV wall thickness and significantly impaired RV diastolic and global function in comparison with the controls or the SHT subjects after the treatment. Furthermore, RV mechanics was also significantly deteriorated in the SHT patients before the treatment. CONCLUSIONS: Subclinical hypothyroidism significantly affected LV and RV structure, systolic, diastolic and global function, and LV and RV mechanics. Levothyroxine replacement therapy significantly improved cardiac structure, function, and mechanics in the SHT patients. PMID- 24217560 TI - Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: a phase II trial. AB - BACKGROUND: This study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB). MATERIAL AND METHODS: A phase II trial was performed in 158 patients with pulmonary TB (145 initially-treated and 13 re-treated) and 133 healthy subjects. Skin testing was carried out by injecting purified protein derivative (PPD) (on left forearm) or recombinant ESAT-6 protein at a dosage of 2, 5, or 10 MUg/mL (on the right forearm) in each subject. Reaction activity and adverse events were monitored at 24, 48, and 72 h following the injection. Receiver operating characteristic curves were plotted to determine the areas under the curves (AUCs) and the cut-off induration diameters for the optimal diagnostic performance. RESULTS: The reaction activity was significantly increased upon recombinant ESAT 6 injection in pulmonary TB patients compared with healthy subjects. In pulmonary TB patients, the reaction was dose-dependent, and at 48 h, 10 MUg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD. The AUCs for a 10 MUg/mL dosage were 0.9823, 0.9552, and 0.9266 for 24 h, 48 h, and 72 h, respectively, and the induration diameters of 4.5-5.5 mm were the optimal trade off values between true positive rates and false positive rates. No serious adverse events occurred in any subjects. CONCLUSIONS: Recombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB. Based on the reaction, performance, safety, and practicability, we recommend that 10 MUg/mL at 48 h with an induration cut-off value of 5.0 mm be used. PMID- 24217561 TI - Synthesis of benzosultams via an intramolecular sp2 C-H bond amination reaction of o-arylbenzenesulfonamides under metal-free conditions. AB - A practical synthetic method for the generation of benzosultams via an intramolecular sp(2) C-H bond amination reaction of o-arylbenzenesulfonamides with PhI(OAc)2-I2 under metal-free conditions is developed. A broad range of substrates are tolerated under mild reaction conditions, affording bioactive benzosultams in good to excellent yields. The resulting benzothiazines could be conveniently transformed into their corresponding iodinated derivatives via electrophilic substitution reactions. PMID- 24217562 TI - Maintaining a healthy body weight is paramount. PMID- 24217563 TI - Detailed illustration of the visual field representation along the visual pathway to the primary visual cortex: a graphical summary. AB - PURPOSE: In the literature, different graphic illustrations are available, which depict different parts of the visual pathway in relation to visual field sectors, to retinal sectors, the layers of the lateral geniculate nucleus (LGN), or sections of the primary visual cortex (V1). However, a complete overview is missing, which may be useful for a more precise differentiation of predominantly ophthalmological from intracerebral diseases. It may also be of interest to investigate additional intracerebral reasons that are involved in impaired vision of largely unknown pathophysiology. METHODS: This work combines the scientific knowledge of partial graphics in one detailed illustration that allows exact follow-up of the neuronal connections from individual visual field sectors to the V1 areas. A selective search for peer-reviewed graphics of the visual pathway was performed in PubMed and Google Pictures. RESULTS: Sixteen different visual field sectors and their 16 corresponding retinal sectors were set in relation to 64 LGN sections and 20 areas of V1. Segmented cross-sectional areas of the optic nerve supplemented the graphical representation of the fiber orientation in relation to the visual field. CONCLUSION: The detailed illustration of the visual field projection along the visual pathway structures may facilitate a more precise calculation of correlations between morphological and functional measurements of ophthalmological and neuroradiological examinations. PMID- 24217564 TI - Solution superstructures: truncated cubeoctahedron structures of pyrogallol[4]arene nanoassemblies. AB - Giant nanocapsules: the solution-phase structures of PgC1Ho and PgC3Ho have been investigated using in situ neutron scattering measurements. The SANS results show the presence of spherical nanoassemblies of radius 18.2 A, which are larger than the previously reported metal-seamed PgC3 hexamers (radius = 10 A). The spherical architectures conform to a truncated cubeoctahedron geometry, indicating formation of the first metal-containing pyrogallol[4]arene-based dodecameric nanoassemblies in solution. PMID- 24217565 TI - [Breast cancer screening in Brazil: there is still time to rethink]. PMID- 24217566 TI - [Maternal mortality in a reference center in the Brazilian Southeast]. AB - PURPOSE: To describe the prevalence of maternal mortality at a tertiary care hospital and to assess its preventability. METHODS: This study, through the analysis of maternal deaths that occurred during the period from 1999 to 2010 at a reference in Campinas--Brazil, CAISM/ UNICAMP, discusses some of the factors associated with the main causes of death and some structural problems of structure of the health services. It is a retrospective descriptive study with evaluation of sociodemographic variables and the medical and obstetric history of women, and the causes of death. RESULTS: The majority of maternal deaths occurred due to direct obstetric (45%) and avoidable (36%) causes, in women with preterm gestation, who delivered by cesarean section (56%) and received various management procedures, including blood transfusion, ICU admission and need for laparotomy and/or hysterectomy. The hospital transfer was associated with the predominance of direct obstetric (19 versus 6, p=0.02) and avoidable causes (22 versus 9, p=0.01). CONCLUSIONS: We conclude that, despite current advances in Obstetrics, infections and hypertensive disorders are still the predominant causes of maternal mortality. We observed an increase of clinical-surgical conditions and neoplasms as causes of death among women during pregnancy. PMID- 24217567 TI - [Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor]. AB - PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value. PMID- 24217568 TI - [Habits and traditions of female college students related to intimate clothing, genital adornments, genital hair removal and sexual practices]. AB - PURPOSE: To describe the practices and care with the genital area of female college students. METHODS: A descriptive analytical study evaluated the habits and traditions of 364 students from the University of Campinas (Unicamp) regarding the use of underwear, body piercings, tattoos, hair removal and sexual practices. A questionnaire with 42 questions assessed the most current practices among female college students. All questions were self answered and the questionnaires, without any identification, were placed in sealed ballot boxes to ensure the confidentiality of information. The responses were tabulated in Microsoft(r) Excel 2007 to obtain univariate analysis. RESULTS: The mean age of the college students in the study was 21 years (SD +/- 2.7), and 84% were white. The volunteers who participated in this study were from the biological science area (50%), the exact science area (29%) or the humanity area (21%). It was observed that 61.8% of the respondents wear cotton panties, but at the same time 75.4% wear tight jeans, and only 18.4% wore no panties when sleeping. Only one participant reported having had genital piercing and none of them reported tattooing. Most female college students do genital waxing, and approximately 1/3 of them do so completely. After hair removal, 2/3 apply an anti-inflammatory and/or moisturizer to the region. Only 62% use condoms and 17.6% use a lubricant during intercourse. Half of them receive oral sex, 17.9% practice anal sex and 26.6% of them report feeling pain during sexual intercourse. Vaginal discharge after intercourse was reported in 25.6% of the cases. CONCLUSION: Young female college students from Brazilian public universities have many inadequate care habits related to their genital area. They do not use genital piercing and tattoos, but report having pain during sexual intercourse and vaginal discharge after sex in a large number of cases. PMID- 24217569 TI - Hofbauer cells morphology and density in placentas from normal and pathological gestations. AB - PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens. PMID- 24217570 TI - [Metabolic profile in women of different body mass indices with polycystic ovary syndrome]. AB - PURPOSE: To characterize and compare clinical, anthropometric and biochemical metabolic variables in patients with polycystic ovary syndrome (PCOS), stratified according to body mass index (BMI). METHODS: A cross-sectional study conducted on 78 women aged 18 to 45 years with a clinical diagnosis of PCOS by the Rotterdam criteria. Patients were stratified according to BMI. The variables analyzed were: age, marital status, physical inactivity, menstrual irregularity, blood pressure (BP), anthropometric measurements, lipid profile, fasting glucose, and hormone measurements. To compare the variables between the different BMI values we used analysis of variance and the Kruskal-Wallis test. The level of significance was set at 5% for all tests. RESULTS: The patients had a mean age of 26.3 years, 79.5% of them were sedentary and 68% had hyperandrogenism. Waist circumference, waist/hip ratio, waist/height ratio and percentage of body fat were higher in the obese group. The markers of cardiovascular risk (CVR - fasting glucose, systolic and diastolic BP and LDL-cholesterol) were directly proportional to BMI, whereas HDL-cholesterol and SHBG were inversely related to BMI. CONCLUSION: The presence of markers of CVR factors increased proportionally to BMI, indicating that the metabolic profile of obese women with PCOS is more unfavorable than that of non obese patients. PMID- 24217571 TI - [Heart rate variability as a method of assessing the autonomic nervous system in polycystic ovary syndrome]. AB - Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with several cardiometabolic risk factors, such as central obesity, insulin resistance, type 2 diabetes, metabolic syndrome, and hypertension. These factors are associated with adrenergic overactivity, which is an important prognostic factor for the development of cardiovascular disorders. Given the common cardiometabolic disturbances occurring in PCOS women, over the last years studies have investigated the cardiac autonomic control of these patients, mainly based on heart rate variability (HRV). Thus, in this review, we will discuss the recent findings of the studies that investigated the HRV of women with PCOS, as well as noninvasive methods of analysis of autonomic control starting from basic indexes related to this methodology. PMID- 24217572 TI - Gunshot wound to the pregnant uterus: case report. AB - Crime and violence have become a public health problem. Pregnant women have not been the exception and gunshot injuries occupy an important place as a cause of trauma. An important fact is that pregnant women, who suffer trauma, are special patients because pregnancy causes physiological and anatomical changes. Management of these patients should be multidisciplinary, by the general surgeon, the obstetrician and the neonatologist. However, even trauma referral centers could neither have the staff nor the ideal training for these specific cases. In this context we present the following case. PMID- 24217573 TI - One-pot synthesis of 1-azaspiro frameworks initiated by photooxidation of simple furans. AB - A range of 1-azaspirocycles, spiroaminals and 1,6-diazaspirocycles has been synthesized, starting from simple and readily accessible furan precursors, using a cascade reaction sequence initiated by singlet oxygen. PMID- 24217574 TI - NOTCH1 expression predicts patient prognosis in esophageal squamous cell cancer. AB - PURPOSE: The prognosis of patients with esophageal cancer remains poor, and the classification of tumor node metastasis has proven insufficient to predict patient prognosis. Therefore, novel predictive markers of esophageal cancer prognosis are needed. Notch receptors and their ligands have been reported to be upregulated in cervical, lung, colon, renal, and pancreatic cancers, but NOTCH1 expression has not been studied in esophageal cancer. METHODS: Expression of NOTCH1 was quantified by real-time reverse transcription-polymerase chain reaction in 55 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We then examined the correlations between NOTCH1 expression, clinicopathological factors, and prognosis in patients with ESCC. RESULTS: The probability of overall survival was significantly lower for patients with high NOTCH1 expression (p = 0.0028; log-rank test). Overexpression of NOTCH1 was identified as a significant and independent prognostic factor (p = 0.0061) in patients who had undergone surgical treatment for ESCCs. The hazard ratio for predicting early death was 4.298 (95% confidence interval 1.515-12.195) for high versus low NOTCH1 expression. CONCLUSIONS: Our data indicate that NOTCH1 may be a candidate molecular prognostic marker and a molecular target for the development of an effective therapeutic intervention for patients with ESCC. PMID- 24217575 TI - Interactions between neuroscience and psychopathology. PMID- 24217576 TI - A perianal erythematous plaque: a quiz. Secondary extramammary Paget's disease from adenocarcinoma of the anorectal region. PMID- 24217577 TI - D538G mutation in estrogen receptor-alpha: A novel mechanism for acquired endocrine resistance in breast cancer. AB - Resistance to endocrine therapy occurs in virtually all patients with estrogen receptor alpha (ERalpha)-positive metastatic breast cancer, and is attributed to various mechanisms including loss of ERalpha expression, altered activity of coregulators, and cross-talk between the ERalpha and growth factor signaling pathways. To our knowledge, acquired mutations of the ERalpha have not been described as mediating endocrine resistance. Samples of 13 patients with metastatic breast cancer were analyzed for mutations in cancer-related genes. In five patients who developed resistance to hormonal therapy, a mutation of A to G at position 1,613 of ERalpha, resulting in a substitution of aspartic acid at position 538 to glycine (D538G), was identified in liver metastases. Importantly, the mutation was not detected in the primary tumors obtained prior to endocrine treatment. Structural modeling indicated that D538G substitution leads to a conformational change in the ligand-binding domain, which mimics the conformation of activated ligand-bound receptor and alters binding of tamoxifen. Indeed, experiments in breast cancer cells indicated constitutive, ligand-independent transcriptional activity of the D538G receptor, and overexpression of it enhanced proliferation and conferred resistance to tamoxifen. These data indicate a novel mechanism of acquired endocrine resistance in breast cancer. Further studies are needed to assess the frequency of D538G-ERalpha among patients with breast cancer and explore ways to inhibit its activity and restore endocrine sensitivity. PMID- 24217578 TI - Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress. AB - In Huntington's disease, as in other neurodegenerative diseases, it was initially thought that insoluble protein aggregates are the toxic species. However, growing evidence implicates soluble oligomeric polyglutamine-expanded huntingtin in cytotoxicity. Here we show that pathogenic huntingtin inhibits endoplasmic reticulum (ER)-associated degradation and induces ER stress before its aggregation into visible inclusions. All three branches of the unfolded protein response are activated. ER stress can be compensated by overexpression of p97/VCP, suggesting its sequestration by pathogenic huntingtin as a main cause. Stress correlates with the presence of huntingtin oligomers and is independent of continual huntingtin synthesis. Stress levels, measured in striatal neurons, are stabilized but only slowly subside on huntingtin aggregation into inclusions. Our results can be explained by the constant conversion of huntingtin monomers to toxic oligomers; large aggregates sequester the former, precluding further conversion, whereas pre-existing toxic oligomers are only gradually depleted. PMID- 24217580 TI - Imaging: Ultrasonography to detect hand and wrist involvement in SSc. PMID- 24217581 TI - Mesenchymal stem cell treatments in rheumatology: a glass half full? AB - Mesenchymal stem cells (MSCs) represent a heterogeneous progenitor cell population derived from various sources, including bone marrow, placental and adipose tissues. These cell populations are being extensively investigated for their regenerative, immunomodulatory and tissue-protective properties, and the therapeutic potential of MSCs is officially being tested in patients suffering from ischaemic, inflammatory, autoimmune and degenerative disorders. Unofficially, hundreds of centres worldwide already offer MSCs as a 'miracle' panacea treatment for almost every known human disease. Data from in vitro and animal models suggest that MSCs administered either locally or systemically are able to home to stressed tissue and indeed deliver a protective effect via predominately paracrine factors. Furthermore, dozens of published uncontrolled clinical trials have demonstrated strikingly positive therapeutic effects of MSCs with little acute toxicity; however, no prospective controlled trials have yet confirmed these findings, with the exception of one randomized controlled trial in renal transplantation. Thus, large prospective controlled trials are urgently needed to better understand MSC-based therapies and define their potential utility in the treatment of rheumatic diseases. Herein, I provide my opinions regarding the progress of MSC therapies to date and highlight issues that need to be addressed in the future. PMID- 24217583 TI - Pain: Could TRPV1-targeted analgesia of OA pain still be feasible? PMID- 24217584 TI - Crystal arthritis: Environment and genetics in gout: a maze for clinicians? PMID- 24217585 TI - Lest we forget: the First World War's terrible toll on New Zealanders. PMID- 24217582 TI - Emerging cell and cytokine targets in rheumatoid arthritis. AB - Despite major progress in the treatment of rheumatoid arthritis (RA), strong unmet medical need remains, as only a minor proportion of patients reach sustained clinical remission. New approaches are therefore necessary, and include manipulation of regulatory T cells, which might be able to restore the disturbed immune system and could even lead to a cure if this restored regulation were to prove sustainable. Logistical and conceptual problems, however, beset this attractive therapeutic approach, including difficulties with ex vivo expansion of cells, specificity of targeting and the optimal time point of administration. Therefore, alternative avenues are being investigated, such as targeting B-cell effector functions and newly identified proinflammatory cytokines. On the basis of success with B-cell depleting therapy using anti-CD20 agents, further treatment modalities are now exploring direct or indirect interference in B-cell mediated immunity with the use of agents directed against other B-cell surface molecules. Novel approaches target intracellular B-cell signalling and regulatory B cells. New cytokine-directed therapies target important proinflammatory mediators such as GM-CSF, new members of the IL-1 family, IL-6 and its receptor, IL-17, IL-20, IL-21, IL-23 as well as synovium-specific targets. This article reviews these emerging cell and cytokine targets with special focus on biologic agents, some of which might reach the clinic soon whereas others will require considerable time in development. Nevertheless, these exciting new approaches will considerably enhance our repertoire in the battle against this potentially devastating disease. PMID- 24217586 TI - "Easy to cure but difficult to detect"--the case for early warning systems in the acute hospital. PMID- 24217587 TI - Fatal injury epidemiology among the New Zealand military forces in the First World War. AB - BACKGROUND: Despite the large mortality burden of First World War (WW1) on New Zealand (NZ) military forces, no analysis using modern epidemiological methods has ever been conducted. We therefore aimed to study injury-related mortality amongst NZ military forces in WW1. METHODS: An electronic version of the Roll-of Honour for NZ Expeditionary Force (NZEF) personnel was supplemented with further coding and analysed statistically. We also performed literature searches to provide context. RESULTS: Out of a total of 16,703 deaths occurring during the war (28 July 1914 to 11 November 1918), injury deaths predominated: 65.1% were "killed in action" (KIA), 23.4% "died of wounds" (DOW), 1.0% were other injuries (e.g. "accidents", drownings, suicides and executions), and 10.5% were other causes (mainly disease). During the course of the war, the annual mortality rate from injury (for KIA + DOW) per 10,000 NZEF personnel in the North Hemisphere peaked at 1335 in 1915 (Gallipoli campaign) and then peaked again in 1917 at 937 (largely the Battle of Passchendaele). Some of the offensive campaigns involved very high mortality peaks (e.g. 2 days with over 450 deaths per day in October 1917). CONCLUSIONS: Participation in First World War was by far the worst fatal injury event in New Zealand's history. Many of these injury deaths could be considered to have been preventable through: better diplomacy (to prevent the war), improved military planning to reduce failed campaigns (e.g. Gallipoli, Passchendaele), earlier use of protective equipment such as helmets, and improved healthcare services. PMID- 24217588 TI - Evaluating the impact of implementing an early warning score system on incidence of in-hospital cardiac arrest. AB - AIM: To evaluate the introduction of an early warning score (EWS) system on incidence of in-hospital adult cardiac arrest. METHODS: A before-after evaluation of an EWS system (in the form of a patient observation chart with escalation protocol) in a 600 bed tertiary teaching hospital in New Zealand during the two 12-month periods between March 2009 and March 2011. Difference in incidence rates was compared using Student's t test. RESULTS: There were 168 cardiac arrests during the 24 month period. The incidence rate of cardiac arrests per 1000 admissions was 4.67 during 2009-2010 and 2.91 during 2010-2011 (mean difference of 1.77, 95%CI 0.59-2.94). The number of cardiac arrests dropped from an average of 8.5 arrests per month during 2009-2010 to 5.5 arrests per month during 2010 2011 following the introduction of ADDS (mean difference 3.0, 95%CI 0.78-5.22). There was no significant increase in the number of medical emergency calls (7.5 calls versus 9.1 calls per month). CONCLUSION: Introduction of an EWS system in addition to an existing cardiac arrest team response decreased the incidence of in-hospital cardiac arrests in a tertiary hospital in New Zealand. PMID- 24217589 TI - Stereotypes do not always apply: findings from a survey of the health behaviours of mental health consumers compared with the general population in New Zealand. AB - AIM: Research suggests that people with mental illness frequently have worse physical health than the general population. Our study sought to investigate the health behaviours of mental health consumers in New Zealand, as we hoped that by clearly describing this group more targeted healthcare could be provided. METHOD: We surveyed 404 adult mental health consumers about their: height and weight, fruit and vegetable intake, exercise activity, smoking, alcohol and drug use. RESULTS: We found that mental health consumers abstained from alcohol more often than those from the general population sample. However, we also found increased obesity, poorer eating habits, less physical activity, and a higher proportion of smokers among mental health consumers. We also found that those who did drink alcohol did so more heavily than drinkers from the general population sample. Finally, there were a number of interesting demographic variations among mental health consumers in terms of their health behaviours. For example, those in the European/Other ethnic group more often consumed an alcoholic drink at least 3 or 4 times a week than those in other ethnic groups, and those in the Pacific group did this less often. CONCLUSIONS: Mental health consumers cannot be stereotyped as a single homogeneous group in relation to their health behaviours. IMPLICATIONS: Health professionals should strongly encourage engagement from mental health populations to identify their physical health behaviours. Individual differences in health behaviours should not be ignored just because a mental illness is present. PMID- 24217590 TI - Introduction of sacral neuromodulation for the treatment of faecal incontinence. AB - INTRODUCTION: Faecal incontinence (FI) is a condition that impairs quality of life and ability to function socially. Over the last 15 years a promising new therapy (sacral neuromodulation, SNM) has been introduced which has been associated with marked improvement in many incontinence symptoms. AIMS: To assess the early results of SNM in Auckland in terms of improved continence in those undergoing implantation of a permanent stimulator, and determine whether these results are comparable to overseas data. METHODS: Patients who met the criteria for SNM; severe faecal incontinence, failure to respond to other measures including biofeedback, dietary modification, and appropriate surgical intervention were offered this treatment. After an initial bowel diary, patients underwent lead placement connected to an external stimulator and only those who responded had an implanted stimulator placed. Results were assessed by repeated bowel diary, QoL scores and continence scores. RESULTS: Of 29 patients who had initial percutaneous stimulation, 27 showed adequate improvement and went on to permanent implanted stimulator. Of these, results were available on 26. The median number of FI episodes per week preoperatively was 7.25. The median post implantation was one. FI episodes improved following SNM by a mean of 12.21 episodes per week (95% confidence interval 4.91 to 19.51, p value=0.002). For those with longer follow up the initial improvement was sustained. There was a mean follow up time of 10.7 months (range 1 to 30 months). CONCLUSION: Early results are encouraging, with a significant improvement in faecal incontinence following SNM. The results in Auckland in terms of improvement in symptom severity and quality of life are significant and comparable to other centres. SNM offers a good alternative for patients with end-stage FI. PMID- 24217591 TI - The Green Lane and Auckland City Hospital cardiac resynchronisation therapy experience. AB - AIM: To evaluate the outcome of cardiac resynchronisation therapy (CRT) in Auckland since its inception in 2000. Outcome measures were periprocedural events including procedure duration, fluoroscopic time, procedure success, complications, and echocardiographic markers of response. METHODS: Retrospective review of those undergoing CRT implantation at Green Lane and Auckland City Hospitals. RESULTS: 159 CRT procedures were performed on 139 patients between 2000 and April 2011. Of all procedures: 63% had new device implants, and 23% were upgraded from a pacemaker or defibrillator to CRT. Mean age 62 years, 77% male, mean left ventricular ejection fraction (LVEF) 25%, mean QRS duration 175 ms, 91% LBBB, 36% ischaemic cardiomyopathy. Mean procedure time 147 min and fluoroscopy time 30 min. Eight patients had significant periprocedural complications (6%), 17 experienced lead displacement (12%), and 15 (11%) had unsuccessful procedures. 46% of patients had complete echocardiographic data, of these LVEF improved by >5% in 52%, and decreased by >5% in 6% over a 16-month follow-up. CONCLUSIONS: Our service performs well with respect to complication rate, though less well when failure of implantation and lead dislodgement are considered. Where complete echocardiographic data was present 52% of our patients derived significant improvement in LVEF. PMID- 24217592 TI - Understanding medication errors in the elderly. AB - Elderly are the most vulnerable population group owing to increased prevalence of chronic diseases and drug consumption. Several characteristics of aging and geriatrics medicine affect drug prescribing for elderly. Thus the selection of appropriate pharmacotherapy for elderly becomes a complex and challenging process. Association of these factors with metabolic changes predisposes the older people to suffer drug interactions and adverse drug events. The objective of this article is to understand the concept, causes and measurement of medication errors in elderly. Various interventions to improve drug prescribing such as educational approaches, geriatric medicine services, computerised prescribing and multifaceted approaches have also been highlighted. In conclusion there is an overwhelming need for optimising the prescribing in elderly through an integrated approach involving physician, pharmacologist, pharmacist and the patient himself. PMID- 24217593 TI - Numerical identity: the creation of tri-parental embryos to correct inherited mitochondrial disease. AB - Inherited mitochondrial disorders affect between 1 in 5000 to 1 in 8000 people. These are a heterogeneous group of maternally-inherited disorders, with an array of outcomes such as heart and liver failure, defects in energy metabolism, blindness, deafness, loss of motor skills and premature death. Recently the Human Fertilisation and Embryology Authority provided advice to the UK Government to permit the use of enucleated donated oocytes with normal (wild-type) mitochondria (a currently prohibited IVF technique) to be used as recipients of nuclear DNA from intending mothers to overcome transmission of mitochondrial disorders. In this short communication we present the basis for this radical new IVF technology, and discuss the implications for its use both in the context of treating a group of inherited disorders and the current New Zealand IVF legislation. PMID- 24217594 TI - Bleeding from gastrointestinal tract recurrence of non-seminomatous germ cell tumour testis, showing temporary response to gemcitabine and oxaliplatin chemotherapy. AB - The first reported case of gemcitabine/oxaliplatin (GemOx) chemotherapy used for recurrent non-seminomatous germ cell tumour of the testis metastatic to the gastrointestinal tract causing uncontrolled bleeding which induced a temporary response. PMID- 24217595 TI - Bilateral plunging ranula: two case reports and a review of the literature. AB - AIM: Presentation of two bilateral plunging ranula cases and then review of the plunging ranula literature to understand current concepts on aetiology, imaging for diagnosis and management. METHOD: A literature review using PubMed (92 papers) and Google Scholar (18 papers) has revealed only 18 cases of bilateral plunging ranulas ever published and with the addition of the two cases presented this makes a total of 20. RESULTS: These cases are reviewed and information related to aetiology and management is presented. The cause appears to be a combination of mylohyoid dehiscence, racial predisposition and previous trauma to the mouth/face or previous oral surgery. CONCLUSION: Plunging ranula are a rare cause of bilateral and unilateral neck swellings but more common in Maori, Polynesian and Asian people. Their cause is multifactorial and ultrasound scan (USS) is the current investigation of choice. Management relies on excision of the sublingual gland with the cystic contents via a trans-oral approach. PMID- 24217596 TI - Medical image. Fibrosing mediastinitis. A rare "mimicker" of lung malignancy. PMID- 24217597 TI - Bowel cancer screening in New Zealand. PMID- 24217598 TI - Prostate cancer screening and ethical use of limited resources. PMID- 24217599 TI - Unusual ECD fragmentation attributed to gas-phase helix formation in a conformationally dynamic peptide. AB - The helix-forming character of a model decapeptide, L4PL4K, is determined in the absence of solvent using ion mobility mass spectrometry, electron capture dissociation and molecular mechanics simulations. Unusual ECD fragmentation patterns dominated by b ions are attributed to helix formation upon electron capture and as a signature of conformational dynamics. PMID- 24217600 TI - History of research on angiogenesis. AB - Over the past 25 years, the number of Medline publications dealing with angiogenesis has increased in a nonlinear fashion, reflecting the interest among basic scientists and clinicians in this field. Under physiological conditions, angiogenesis is regulated by the local balance between endogenous stimulators and inhibitors of this process. In tumor growth, there is an imbalance between endogenous stimulator and inhibitor levels, leading to an 'angiogenic switch'. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. This paper offers an account of the most relevant discoveries in this field of biomedical research. PMID- 24217601 TI - Immune cells as a source and target of angiogenic and lymphangiogenic factors. AB - Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. Immune and inflammatory cells can contribute to these processes by multiple mechanisms: directly by producing a broad array of angiogenic growth factors, and indirectly by secreting several cytokines, chemokines and other mediators able to coordinate the cell-cell interactions. Immune cells can stimulate or inhibit angiogenesis/lymphangiogenesis, depending on their activation status and subset specificity. We summarize recent findings reporting the expression and activity of angiogenic and lymphangiogenic factors and their receptors and coreceptors in immune cells. It is evident that modulation of angiogenesis and lymphangiogenesis by the innate and adaptive immune cells (mast cells, macrophages, dendritic cells, basophils, eosinophils, and some subsets of T cells) is a highly complex process not yet completely understood. PMID- 24217602 TI - Neuropilins: role in signalling, angiogenesis and disease. AB - Neuropilins (NRPs) are co-receptors for class 3 semaphorins and for members of the vascular endothelial growth factor (VEGF) family of angiogenic cytokines. Genetic analysis of the role of NRPs in mice shows that NRP1 is essential for embryonic neuronal pathfinding and cardiovascular development, mediated via semaphorins and VEGF, respectively, while NRP2 has a more restricted role in neuronal patterning and lymphangiogenesis. NRPs are thought to mediate functional responses, most importantly cell migration, as a result of complex formation with other receptors, such as plexins in the case of semaphorins and the VEGF receptor, VEGFR2, resulting in enhanced signalling via some intracellular pathways. Recent findings indicate that NRPs may have important biological roles in other physiological and disease-related processes. In particular, NRPs are highly expressed in diverse tumour cell lines and human neoplasms and have been implicated in several biological processes regulating tumour growth in vivo, suggesting that NRP1 may be a future therapeutic target in cancer. PMID- 24217603 TI - Class 3 semaphorin in angiogenesis and lymphangiogenesis. AB - Semaphorins were originally identified as axon guidance molecules involved in the development of the neuronal system. However, accumulating evidences have clearly demonstrated that the semaphorin system is not restricted to the brain but supports functions of other organs. Here, we review the rapidly emerging functions of sempahorins and, in particular class 3 semaphorin, in vascular and lymphatic systems during the development, tumor angiogenesis and ischemic revascularization. PMID- 24217604 TI - Angiogenic and antiangiogenic chemokines. AB - Chemokines are a family of vertebrate-specific, small-secreted molecules that were originally identified as mediators of leukocyte migration and tissue positioning during the immune response. Subsequently, chemokines were discovered to control movement also of endothelial cells and other cell types in many different contexts. The human chemokine system comprises about 50 chemokines and more than 20 receptors belonging to the seven-transmembrane receptor family. In the present chapter, we review the literature supporting a role for chemokines in angiogenesis and lymphangiogenesis. We highlight that chemokines exert both pro- and antiangiogenic roles either by acting directly on endothelial cells or by recruiting leukocytes that, in turn, secrete angiogenic mediators. This latter mode of action is possibly the most relevant in tumor angiogenesis. Finally, we explore the angiogenic properties of nonchemokine chemoattractant molecules. PMID- 24217605 TI - Role of uPA/uPAR in the modulation of angiogenesis. AB - Blood vessels connect all districts of the body and allow blood oxygen and nutrients to reach every cell in the organism. Dysregulation of blood vessel formation or functionality is the origin of a large number of diseases. During new vessel formation, endothelial cells degrade their basement membrane, migrate into the interstitial matrix and proliferate. Migrating endothelial cells need to be polarized, to focus at their leading edge the proteolytic machinery, which is essential for extracellular matrix degradation; thus, proteases and their receptors play a crucial role in angiogenesis. The urokinase-mediated plasminogen activation system is a complex system of serine proteases strongly involved in angiogenesis. The plasminogen activation system includes plasminogen/plasmin, activators, inhibitors and cell receptors. In the last decades, a large body of evidence has clearly indicated that the role of this system is not limited to extracellular matrix proteolysis but can contribute to all phases of the angiogenic process. PMID- 24217606 TI - Neutrophil-derived cytokines involved in physiological and pathological angiogenesis. AB - Increasing data from the literature point to a neutrophil-mediated role via cytokine production in several aspects of mammalian biology, including angiogenesis. In such regard, neutrophils have been shown to synthetize and release a number of molecules able to promote, directly or indirectly, the growth and migration of endothelial cells, in turn inducing the formation of new blood vessels from preexisting ones. Interestingly, neutrophil-derived cytokines can be involved either in physiological or in pathological angiogenesis, depending on either the functioning or dysregulation of sophisticated interplays among different cell types, extracellular matrix and soluble mediators within the microenvironment. Our review resumes the most interesting studies elucidating the role of neutrophil-derived cytokines in human physiological and pathological angiogenesis. When appropriate, supporting observations generated in animal models will be also mentioned. Particular emphasis will be given to VEGF and PK2/Bv8, rather than CXCL8/IL-8 and OSM. We will also discuss the potential role of neutrophil-derived cytokines such as FGF2, Ang1 and IL-17, whose roles in angiogenesis - albeit anticipated - remain to be elucidated. PMID- 24217607 TI - Roles of eosinophils in the modulation of angiogenesis. AB - Chronic allergic inflammatory diseases are characterized by tissue damage with consequent remodeling including fibrosis and angiogenesis. Eosinophils are usually recruited to sites of allergic inflammation infiltrating the tissues as fully differentiated cells. In the last two decades, these cells have been characterized as a proangiogenic. The inadequate blood supply together with a high consumption of oxygen by the infiltrated cells is the main cause of tissue hypoxia in inflammation. Infiltrated eosinophils respond to hypoxia by increasing their viability and proangiogenic potential and regulate the expression of receptors particularly CD300a. PMID- 24217608 TI - Regulatory T cells, leptin and angiogenesis. AB - Regulatory T cells (Treg cells) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Excess body weight and obesity are typified by 'low-degree' chronic inflammation and are associated with an increased risk of atherosclerosis, diabetes, fatty liver disease, autoimmune diseases and cancer. All these pathological conditions are characterized by chronic inflammation, abnormal cytokine production, elevated acute-phase reactants, and the activation of several inflammatory signaling pathways. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. Leptin represents a link among metabolic disorders and immune tolerance; indeed, leptin can negatively affect the generation and proliferation of Treg cells, key players in this context. Treg cells play also a central role in tumor progression; different reports have proposed that tumor microenvironment can induce the recruitment of Treg cells which can promote tumor tolerance and angiogenesis through expression of suppressive molecules, cytokines and angiogenic factors (i.e. vascular endothelial growth factor, leptin). This work aims to discuss some of the most recent advances on the relationship between angiogenesis, leptin and immune tolerance, focusing on the role of Treg cell function in this context. PMID- 24217609 TI - Angiogenesis as a therapeutic target for obesity and metabolic diseases. AB - White adipose tissue constantly experiences expansion and shrinkage during the entire adulthood, depending on the metabolic status of the host. Emerging evidence demonstrates that the plasticity of white adipose tissue is tightly controlled by the adipose vasculature, which may grow or regress to coordinate adipose tissue metabolism. In metabolically active brown adipose tissue, an exceedingly high density of blood vessels may perfuse oxygen for energy consumption. Consequently, modulation of vascular density and functions in both white adipose tissue and brown adipose tissue may offer an exciting opportunity for therapeutic interference of obesity and metabolic disease. In fact, in several preclinical obese animal models, angiogenesis modulators significantly alter body weights and metabolic rates of the host, implying a possible new therapeutic option for treatment of these common human diseases. Additionally, angiogenesis modulators may significantly regulate insulin sensitivity and the development of type II diabetes. In fact, antiangiogenic or angiogenic drugs have been implicated for treatment of diabetes and diabetes-related complications. Given the therapeutic values of angiogenesis modulators in preclinical animal models, it is reasonable to speculate these angiogenesis modulators may eventually be used for treatment of human obesity and metabolic disorders. PMID- 24217610 TI - Angiogenesis in multiple myeloma. AB - Angiogenesis is a constant hallmark of multiple myeloma progression and has prognostic potential. Multiple myeloma cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype, both at primary and secondary tumor sites. The pathophysiology of multiple myeloma-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment cells. A direct involvement of bone marrow macrophages and mast cells in vasculogenic mimicry has been demonstrated, thus contributing together with circulating endothelial cells and endothelial precursor cells to the multiple myeloma neovascularization. The role of host cells or the niche microenvironment and extracellular matrix represents an intense area of research, finalized at a better understanding of the pathophysiological modifications of the complete tumor entity, i.e. malignant cells and microenvironment. PMID- 24217611 TI - Angiogenesis inhibitors in the treatment of prostate cancer. AB - Prostate cancer is the most common cancer in men in the United States and is the second most common cause of death. While treatment options in early stage disease are curative in intent, treatment of metastatic prostate cancer remains challenging. Although, several new and promising treatment options exploiting novel targets have permeated the therapeutic landscape in recent years, another viable target for therapy is tumor angiogenesis. Many antiangiogenic agents are under development and some are currently under investigation in clinical trials. PMID- 24217612 TI - Therapeutic perspectives in vascular remodeling in asthma and chronic obstructive pulmonary disease. AB - In chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), changes in bronchial microvasculature are present and contribute to airway wall remodeling. Angiogenesis and vascular leak seem to be prevalent in asthma, while vasodilatation and vascular leak seem to be prevalent in COPD. The functional meaning of bronchial vascular remodeling is not completely known. The increase in vessel number and size as well as the vascular leakage may concur to the thickening of the airway wall and to the narrowing of the bronchial lumen. Accordingly, pharmacological control of bronchial vascular remodeling may be crucial for symptom control in asthma and COPD. In asthmatic airways, steroids can downregulate vascular remodeling by acting on proangiogenic factors, whereas long-acting beta2-agonists seem to be mostly effective in decreasing vascular permeability. In COPD, there is less available experimental evidence on the effect of the currently used drugs on airway microvascularity changes. Importantly, vascular endothelial growth factor, the most specific grow factor for vascular endothelium, is crucially involved in the pathophysiology of the airway vascular remodeling, both in asthma and COPD. The inhibition of vascular endothelial growth factor and its receptors has the potential for the treatment of the vascular changes in the airway wall. PMID- 24217613 TI - Angiogenesis, lymphangiogenesis and clinical implications. Preface. PMID- 24217614 TI - Chris Bakal: Look and learn. Interviewed by Caitlin Sedwick. PMID- 24217615 TI - Axonal spectrins: all-purpose fences. AB - A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction. This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors. In this issue, Zhang et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201308116) show that axonal betaII spectrin maintains the diffusion barrier at the paranodal junction. Thus, betaII spectrin serves to compartmentalize the membrane of myelinated axons at specific locations that are determined either intrinsically (i.e., at the axonal initial segment), or by axoglial contacts (i.e., at the paranodal junction). PMID- 24217617 TI - Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity. AB - Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons. PMID- 24217616 TI - Cell biology in neuroscience: Death of developing neurons: new insights and implications for connectivity. AB - The concept that target tissues determine the survival of neurons has inspired much of the thinking on neuronal development in vertebrates, not least because it is supported by decades of research on nerve growth factor (NGF) in the peripheral nervous system (PNS). Recent discoveries now help to understand why only some developing neurons selectively depend on NGF. They also indicate that the survival of most neurons in the central nervous system (CNS) is not simply regulated by single growth factors like in the PNS. Additionally, components of the cell death machinery have begun to be recognized as regulators of selective axonal degeneration and synaptic function, thus playing a critical role in wiring up the nervous system. PMID- 24217618 TI - Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis. AB - Cellular cholesterol levels are controlled by endoplasmic reticulum (ER) sterol sensing proteins, which include Scap and Insig-1. With cholesterol sufficiency, Insig inhibits the activation of sterol regulatory element binding proteins (SREBPs), key transcription factors for cholesterol and fatty acid biosynthetic genes, by associating with Scap-SREBP complexes to promote their ER retention. Here we show that the multimeric ER proteins erlins-1 and -2 are additional SREBP regulators. Depletion of erlins from cells grown with sterol sufficiency led to canonical activation of SREBPs and their target genes. Moreover, SREBPs, Scap, and Insig-1 were physically associated with erlins. Erlins bound cholesterol with specificity and strong cooperativity and responded to ER cholesterol changes with altered diffusional mobility, suggesting that erlins themselves may be regulated by cholesterol. Together, our results define erlins as novel cholesterol-binding proteins that are directly involved in regulating the SREBP machinery. We speculate that erlins promote stability of the SREBP-Scap-Insig complex and may contribute to the highly cooperative control of this system. PMID- 24217619 TI - Membrane domain organization of myelinated axons requires betaII spectrin. AB - The precise and remarkable subdivision of myelinated axons into molecularly and functionally distinct membrane domains depends on axoglial junctions that function as barriers. However, the molecular basis of these barriers remains poorly understood. Here, we report that genetic ablation and loss of axonal betaII spectrin eradicated the paranodal barrier that normally separates juxtaparanodal K(+) channel protein complexes located beneath the myelin sheath from Na(+) channels located at nodes of Ranvier. Surprisingly, the K(+) channels and their associated proteins redistributed into paranodes where they colocalized with intact Caspr-labeled axoglial junctions. Furthermore, electron microscopic analysis of the junctions showed intact paranodal septate-like junctions. Thus, the paranodal spectrin-based submembranous cytoskeleton comprises the paranodal barriers required for myelinated axon domain organization. PMID- 24217620 TI - The histone demethylase LSD1/KDM1A promotes the DNA damage response. AB - Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). We show that LSD1 is recruited directly to sites of DNA damage. H3K4 dimethylation, a major substrate for LSD1, is reduced at sites of DNA damage in an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. Although loss of LSD1 did not affect the initial formation of pH2A.X foci, 53BP1 and BRCA1 complex recruitment were reduced upon LSD1 knockdown. Mechanistically, this was likely a result of compromised histone ubiquitylation preferentially in late S/G2. Consistent with a role in the DDR, knockdown of LSD1 resulted in moderate hypersensitivity to gamma irradiation and increased homologous recombination. Our findings uncover a direct role for LSD1 in the DDR and place LSD1 downstream of RNF168 in the DDR pathway. PMID- 24217621 TI - A novel chromatin tether domain controls topoisomerase IIalpha dynamics and mitotic chromosome formation. AB - DNA topoisomerase IIalpha (Topo IIalpha) is the target of an important class of anticancer drugs, but tumor cells can become resistant by reducing the association of the enzyme with chromosomes. Here we describe a critical mechanism of chromatin recruitment and exchange that relies on a novel chromatin tether (ChT) domain and mediates interaction with histone H3 and DNA. We show that the ChT domain controls the residence time of Topo IIalpha on chromatin in mitosis and is necessary for the formation of mitotic chromosomes. Our data suggest that the dynamics of Topo IIalpha on chromosomes are important for successful mitosis and implicate histone tail posttranslational modifications in regulating Topo IIalpha. PMID- 24217622 TI - Opposing actions of septins and Sticky on Anillin promote the transition from contractile to midbody ring. AB - During cytokinesis, closure of the actomyosin contractile ring (CR) is coupled to the formation of a midbody ring (MR), through poorly understood mechanisms. Using time-lapse microscopy of Drosophila melanogaster S2 cells, we show that the transition from the CR to the MR proceeds via a previously uncharacterized maturation process that requires opposing mechanisms of removal and retention of the scaffold protein Anillin. The septin cytoskeleton acts on the C terminus of Anillin to locally trim away excess membrane from the late CR/nascent MR via internalization, extrusion, and shedding, whereas the citron kinase Sticky acts on the N terminus of Anillin to retain it at the mature MR. Simultaneous depletion of septins and Sticky not only disrupted MR formation but also caused earlier CR oscillations, uncovering redundant mechanisms of CR stability that can partly explain the essential role of Anillin in this process. Our findings highlight the relatedness of the CR and MR and suggest that membrane removal is coordinated with CR disassembly. PMID- 24217624 TI - Digitalis use in contemporary clinical practice: refitting the foxglove. PMID- 24217623 TI - The midbody ring scaffolds the abscission machinery in the absence of midbody microtubules. AB - Abscission completes cytokinesis to form the two daughter cells. Although abscission could be organized from the inside out by the microtubule-based midbody or from the outside in by the contractile ring-derived midbody ring, it is assumed that midbody microtubules scaffold the abscission machinery. In this paper, we assess the contribution of midbody microtubules versus the midbody ring in the Caenorhabditis elegans embryo. We show that abscission occurs in two stages. First, the cytoplasm in the daughter cells becomes isolated, coincident with formation of the intercellular bridge; proper progression through this stage required the septins (a midbody ring component) but not the membrane-remodeling endosomal sorting complex required for transport (ESCRT) machinery. Second, the midbody and midbody ring are released into a specific daughter cell during the subsequent cell division; this stage required the septins and the ESCRT machinery. Surprisingly, midbody microtubules were dispensable for both stages. These results delineate distinct steps during abscission and highlight the central role of the midbody ring, rather than midbody microtubules, in their execution. PMID- 24217625 TI - One-pot formation of fluorescent gamma-lactams having an alpha-phosphorus ylide moiety through three-component alpha(delta')-Michael reactions of phosphines with an enyne and N-tosyl aldimines. AB - We demonstrate a straightforward synthesis of gamma-lactams possessing an alpha phosphorus ylide moiety from assembly of phosphines, N-tosyl aldimines and an enyne through an initial alpha(delta')-attack of phosphines to an enyne in up to 79% yield. The investigated multicomponent reaction tolerates a variety of triarylphosphines and electron-poor aldimines to give gamma-lactams in one pot. One of the lactams, with the tri(p-tol)phosphine and 4-cyanophenyl moiety, exhibits fluorescence emission at 447 nm with a quantum yield of 0.11. PMID- 24217626 TI - Heavy metal pollution and potential ecological risks in rivers: a case study from southern Italy. AB - We monitored heavy metal (As, Cd, Hg, and Pb) concentrations in surface water, sediments, and oligochaetes in four major rivers in Calabria (southern Italy) over the course of 1 year. As, Cd, and Pb showed accumulation factors of 10(3) 10(5) for water to sediment and 1-10 for sediment to oligochaetes. Hg showed a water to sediment accumulation factor of 10-100. Finally, Hg concentrations exceeded the Italian quality standard for freshwater in all of the rivers, and As concentrations in sediments exceeded the respective Canadian standard. However, the application of an ecological risk assessment method indicated low risks for all monitored rivers. PMID- 24217627 TI - Fever and rash in children: important diagnostic considerations. AB - The association of fever with illness has been known for years. A febrile child may have rash, and physicians need to know when this symptom combination is a benign versus a pathologic clinical presentation. In other terms, potential etiologies are either infectious or non-infectious. With scrupulous, methodical history taking and careful, serial physical examination, the treating physician will find hints to assess and solidify an appropriate diagnosis, and chose an appropriate treatment. PMID- 24217628 TI - Advances and challenges in the management and prevention of community-acquired pneumonia. AB - Community-acquired pneumonia (CAP) is a common ailment in childhood, and can be associated with significant morbidity and mortality. The introduction of vaccines led to a decline in pneumonia hospitalizations, although gains have been offset by emerging challenges. In addition, appropriate antibiotic management is complicated by the inability and reluctance to perform invasive tests. This review explores the advances made, as well as the new challenges subsequently posed, in the management and prevention of CAP, with emphasis on vaccine preventable pneumonia, specifically Streptococcus pneumoniae. PMID- 24217629 TI - The quality of life in developing age children with celiac disease. AB - AIM: The moments that follow the diagnosis of celiac disease and the early stages of the gluten-free diet are extremely difficult and complex for parents and child, because they face an important change punctuated by self-denial and deprivation. The main objective of this research is to assess the impact of celiac disease on quality of life in subjects in developmental age, taking into account the perceptions of parents about the child's illness, with the aim to highlight the effect of disease on the child and the entire family. METHODS: The study included both parents of 45 children aged between 2 and 10 years, with established celiac disease. To evaluate the effect of celiac disease on the lifestyle of affected children and their families has been used, after having adapted to the Italian context, the Impact Scale of Childhood Diseases of Hoare and Russell (1995). This study shows that celiac disease is a condition that has a significant impact on both the child and his family. RESULTS AND CONCLUSION: The results obtained by administration of Impact Scale of Childhood Diseases to parents showed that subjects in developmental age with celiac disease could have difficulty on emotional level that affect child development and the whole family context. Acceptance of the illness by the child depends mainly by how much and how this has been accepted by parents. PMID- 24217630 TI - Glioneuronal tumors and epilepsy in children: seizure outcome related to lesionectomy. AB - AIM: Glioneuronal tumors (especially gangliogliomas and dysembryoplastic neuroepithelial tumors) are an increasingly recognised cause of drug-resistant epilepsy in children. The optimal surgical strategy (lesionectomy vs. extended resection of epileptogenic peritumoral areas) to obtain seizure control has not been fully established. Our aim was to analyze the post-surgical seizure outcome in children with epileptogenic glioneuronal tumors related to lesionectomy. METHODS: The clinical data were collected through a database. Video-EEG and MRI were performed in all patients pre-operatively and at the follow-up. RESULTS: Our series included 22 patients. The age range at surgery was 10 months-16 years (mean: 6.5+/-4.5 years). Epilepsy duration ranged 1-78 months (mean: 11.6+/ 17.0). There were complex partial seizures in 14 cases, simple partial seizures in 6 patients and generalized epilepsy in 2. Gross-total surgical removal was achieved in 15 (68.2%) patients. At the last follow-up (mean 4.7 years), 20 (90.9%) patients were seizure-free (Engel Class I) and two (9.1%) were Engel Class III. Six out of seven (85.7%) patients with subtotal removal were Engel Class I. Statistical analysis failed to detect any difference between seizure outcome (Engel Class) and tumor type (DNT vs. GG; P=1.00) or location (temporal vs. non temporal; P=0.51), and extension of the resection (total vs. subtotal; P=1.00). CONCLUSION: Primary aim of the surgery for epileptogenic glioneuronal tumors is to remove the lesion and to obtain a complete seizure control. However, if a complete tumor resection cannot be carried out, a subtotal removal of the lesion can equally provide satisfactory results. PMID- 24217631 TI - Surgery checklist implementation to reduce clinical risk in the pediatric operating room. AB - AIM: The aim of this prospective cohort study was to conduct a proactive analysis of procedural errors as revealed after implementation of a surgical safety checklist in the pediatric operating room of the Maggiore della Carita University Hospital, Novara. A further aim was to determine the effect the checklist had on the reduction, prevention, and protection against clinical risk in this setting. METHODS: A "Checklist for Patient Safety in the Pediatric Operating Room" was derived from documentation in the international literature and implemented in June 2011. All data were collected by a single observer. RESULTS: In all, 61 checklists were compiled. Analysis revealed 189 errors (absolute frequency), with the highest error incidence (59.78%) recorded for the sign-out phase (percentage cumulative frequency). Two categories of events were distinguished (surgical and orthopedic) and compared. The absolute frequency of near-miss events (n=168) and adverse events (n=21) was then broken down into the five phases of checklist compilation. The percentage cumulative frequency of near-miss was 88.89% and that of adverse events was 11.11%. CONCLUSION: Safety checklist implementation led to reduction, prevention and protection against adverse events with patient injury in 88.89% of cases. The error incidence in this pediatric operating room was lower than the average rates published in the literature. PMID- 24217632 TI - [Cognitive, emotional and behavioral development of VLBW and ELBW preterm infants: diagnostic and therapeutic follow-up at preschool age]. AB - AIM: Aims of the present study ware: to identify in preterm children of 4-6 years of age outcomes concerning cognitive, linguistic, emotional and behavioral development; to develop a therapeutic-rehabilitative project for those children in collaboration with the family and school. METHODS: The study enrolled 20 children born prematurely at <=32 weeks of gestational age and/or with a weight <=1500 g, 12 VLBW (7 male e 5 female), 8 ELBW (4 male e 4 female), hospitalized at Novara Hospital "Maggiore della Carita" during the years 2003 and 2004, without severe outcomes. Psychodiagnostic evaluation was performed with standardized tests. On the final report results were discussed with parents, with specific indications for families and schools. Follow-up was at 6 months. Statistical elaboration of data was performed using Spss (Statistical Package for Social Sciences) version 16. RESULTS: Normal cognitive level resulted from the Griffiths Scale, without significant differences between VLBW and ELBW. The overall lowest score, in the "performance" subscale, especially for ELBW, was correlated with Vineland Scales (low scores in the subscales "everyday skills" and "motor ability"). The highest scores were detected in the "linguistic" subscale of the Griffiths Scales and in the "Communication" subscale of the Vineland Scales. The results at Bus Story Test (narrative language) were lower than average for that age. CBCL and TRF do not demonstrate clinical results in the emotional-behavioural area, but the teachers give a more critical assessment. Difficulties in emotional self-regulation interfere in the test, in the separation from the parents and in socializing. CONCLUSION: Monitoring development before starting primary school helps to discover potential problems and to activate supportive interventions. Early interventions allow to control and contain academic failure at school, which could have a negative impact on the child's image of himself and on the perception that the parents and school could have. PMID- 24217633 TI - ["A minute for life": resuscitation techniques in infants with risk for sudden infant death syndrome. Development of an instructional video for parents]. AB - AIM: The present study describes a project carried out in the Center for SIDS/ALTE of the Pediatric Clinic of Varese, targeted to deliver and provide parents with a movies on PBLS titled "A Minute for Life". The impact on the parent was evaluated by applying a questionnaire. METHODS: The movie "A Minute for Life" was given to 308 parents (122 fathers, mean age 35.2 and 186 mothers, mean age 28.4). All parents completed a questionnaire based on 4 parameters: 1. clarity of the content presented; 2. anxiety felt while watching the movie clip 3. reassurance related to their ability to review other times the movie; 4. the perception of its usefulness. RESULTS: Regarding the clarity of content, the results provide evidence that 231 parents (75% of the sample) rated him "very clear", while 77 subjects (25%) considered it "quite clear". On the possibility of being able to have at home, 277 parents (90% of subjects) believed it would be very reassuring to see it back Home. According to 231 parents (75% of the sample) the vision of the movie does not convey anxiety, while 77 of them (25% of subjects) felt slightly concerned in relation to vision. With regard to the overall assessment of the movie, all parents (308, 100% of the sample) agreed about its extreme usefulness. CONCLUSION: Our study opens the way for further prospective studies regarding the appropriateness and usefulness of the movie. It's also important to consider the release of the movie to all new parents and the possibility of giving first aid courses open to all those who want to be able to act with promptness and expertise if and when necessary. PMID- 24217634 TI - [Psycho-organic diseases in children and adolescents affected by pediatric neoplasms]. AB - At Pediatric Oncology Centers, psychological intervention and psychotherapy are generally offered to children and adolescents for supporting their adjustment to disease and treatment. The clinical practice, however, point out that cognitive and emotional symptoms, such as psychic distortions, fatigue, anxiety, irritability and depression, are sustained by biological mechanisms connected with disease and treatment and not respondent to psychological consultation and to other psychosocial resources. These manifestations could interfere with treatment or with the long-term adjustment and call for psychopharmacological treatments. Biological factors able to cause these alterations are not yet studied in depth in clinical tradition and scientific literature on the integration of psychological and psychopharmacological intervention in pediatric oncology is still poor. In this paper organic components of psychic and behavioral alterations in the course of disease are illustrated, considering the symptoms, causes and possible remedies in the light of the most recent interdisciplinary views. The main mechanism connected with oncologic treatments - chemotherapy, surgery, radiotherapy - and responsible for psycho-organic alterations in children and adolescent with cancer are also described. PMID- 24217635 TI - Brand new SPINK1 and CFTR mutations in a child with acute recurrent pancreatitis: a case report. AB - We report a case of a 2,5 years old female, referred to our center for pancreatitis. Medical investigation revealed history of acute recurrent pancreatitis (ARP) since 1 year of age. Family history was negative for pancreatitis. Abdominal ultrasonography and magnetic resonance excluded both biliary tract stenosis and anatomic abnormalities. Calcium metabolic disorders, viral and bacterial infections were ruled out. Molecular sequencing of CFTR revealed heterozygosis for the mutation S1235R, a CFTR-related disorders associated mutation. Fecal elastase-1 (E1) was 529 MUg/gr feces (normal value 200 500 MUg/gr feces). No mutation of PRSS1 gene was detected but heterozygosity for p.Lys41Asn (c.123G>C), a new mutation of SPINK1 gene, was revealed. We speculate that the association of both SPINK1 and CFTR gene mutations may be responsible of ARP in our patient. Further studies need to better elucidate the role of genetic factors in ARP, as well as the influence of environmental factors. PMID- 24217636 TI - [Craniopharyngioma in children: importance of a multidisciplinary approach and therapeutic strategies in the treatment of relapsing]. AB - The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease. PMID- 24217637 TI - Body fat distribution and adipokine secretion are not associated with diabetic retinopathy in patients with type 2 diabetes mellitus. AB - AIMS: The link between diabetic retinopathy (DR) and adipokines is controversial. Some studies suggest that visceral fat and adipokines could be additional risk factors for DR. The aim of this study was to determine the relationship between abdominal fat or adipokine secretion and DR in patients with type 2 diabetes mellitus (DM). METHODS: A total of 179 patients with type 2 DM were included. Each patient underwent measurement of plasma adiponectin and leptin and an evaluation of body fat distribution (visceral and subcutaneous) with MRI. The severity of DR was evaluated according to the classification of the American Academy of Ophthalmology. Patients were classified in 3 groups: absence of DR, mild and moderate DR, and advanced DR (severe, proliferative and laser-treated DR). RESULTS: There were no significant differences between the 3 groups for adiponectin, leptin and visceral or subcutaneous fat accumulation. Patients with DR had a mean duration of diabetes, serum creatinine concentration and percentage of macroalbuminuria significantly higher than patients without DR (p < 0.001, p = 0.003 and p < 0.001, respectively). Serum adiponectin increased with the diabetic nephropathy stage (p = 0.007). CONCLUSIONS: Our study suggests that body fat distribution and adipokine secretion are not associated with DR in patients with type 2 DM. PMID- 24217639 TI - Cationic half-sandwich quinolinophaneoxazoline-based (eta6-p-cymene)ruthenium(II) complexes exhibiting different chirality types: synthesis and structural determination by complementary spectroscopic methods. AB - Novel, optically pure 2-{4-methyl[2]paracyclo[2](5,8)quinolinophan-2-yl}-4 aryl/alkyloxazolines (QUIPHANOX) exhibiting both planar and central chirality have been prepared by reacting (Rp)- and (Sp)-2-cyano-4 methyl[2]paracyclo[2](5,8)quinolinophane with 2-aryl/alkyl-2-aminoethanols. The reaction of each of the above N,N-ligands with [Ru(eta(6)-p-cymene)Cl2]2 in methanol, in the presence of either NH4PF6 or NaBPh4, gave the corresponding half sandwich [(eta(6)-p-cymene)Ru(QUIPHANOX)Cl](+)Y(-), (Y(-) = PF6(-), BPh4(-)) as stable complex salts exhibiting planar and carbon- and metal-centered chirality. The unknown absolute configuration (AC) at the metal was determined by (1)H NMR and by theoretical calculations of electronic circular dichroism (ECD) spectra and subsequently confirmed by crystallographic X-ray analysis. (Rp) and (Sp) ligands afforded (RRu)- and (SRu)-configured complexes, respectively, independent of the AC at the chiral carbon of the oxazoline moiety. PMID- 24217638 TI - Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex. AB - OBJECTIVES: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. METHODS: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. RESULTS: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. CONCLUSION: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability. PMID- 24217640 TI - Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression. AB - Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin's interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors--transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes--through its sequential binding to AP-2 and AP-3A. PMID- 24217641 TI - Photocatalytic reforming of glucose under visible light over morphology controlled Cu2O: efficient charge separation by crystal facet engineering. AB - Multifaceted Cu2O with controlled crystal facet exposure was synthesized via a facile one-step method. It was found that photogenerated electrons prefer to accumulate on high index planes, while holes tend to migrate to {100} facets of a Cu2O polyhedron, leading to efficient charge separation and enhanced photocatalytic reforming of glucose. PMID- 24217642 TI - Cancelled stereotactic biopsy of calcifications not seen using the stereotactic technique: do we still need to biopsy? AB - OBJECTIVE: To determine the frequency of cancelled stereotactic biopsy due to non visualisation of calcifications, and assess associated features and outcome data. METHODS: A retrospective review was performed on 1,874 patients scheduled for stereotactic-guided breast biopsy from 2009 to 2011. Medical records and imaging studies were reviewed. RESULTS: Of 1,874 stereotactic biopsies, 76 (4 %) were cancelled because of non-visualisation of calcifications. Prompt histological confirmation was obtained in 42/76 (55 %). In 28/76 (37 %) follow-up mammography was performed, and 7/28 subsequently underwent biopsy. Of 27 without biopsy, 21 (78 %) had follow-up. Nine cancers (9/49, 18 %) were found: 6 ductal carcinoma in situ (DCIS), 3 infiltrating ductal carcinoma (IDC). Of 54 patients with either biopsy or at least 2 years' follow-up, 9 (17 %) had cancer (95 % CI 8-29). Cancer was present in 7/42 (17 %, 95 % CI 7-31 %) lesions that had prompt histological confirmation (DCIS = 5, IDC = 2) and in 2/28 (7 %, 95 % CI 0.8-24 %) lesions referred for follow-up (DCIS = 1, IDC = 1). Neither calcification morphology (P = 0.2), patient age (P = 0.7), breast density (P = 1.0), personal history (P = 1.0) nor family history of breast cancer (P = 0.5) had a significant association with cancer. CONCLUSION: Calcifications not visualised on the stereotactic unit are not definitely benign and require surgical biopsy or follow-up. No patient or morphological features were predictive of cancer. KEY POINTS: * Half of cancelled stereotactic biopsies were due to non-visualisation of calcified foci. * This reflects the improved detection of calcifications by digital mammography. * Calcifications too faint for the stereotactic technique require alternative biopsy or follow-up * 17 % of patients with biopsy or at least 2 years' follow-up had cancer. * No patient/morphological features were found to aid selection for re-biopsy vs. follow-up. PMID- 24217643 TI - 320-row CT coronary angiography predicts freedom from revascularisation and acts as a gatekeeper to defer invasive angiography in stable coronary artery disease: a fractional flow reserve-correlated study. AB - OBJECTIVES: To determine the accuracy of 320-row multidetector coronary computed tomography angiography (M320-CCTA) to detect functional stenoses using fractional flow reserve (FFR) as the reference standard and to predict revascularisation in stable coronary artery disease. METHODS: One hundred and fifteen patients (230 vessels) underwent M320-CCTA and FFR assessment and were followed for 18 months. Diameter stenosis on invasive angiography (ICA) and M320-CCTA were assessed by consensus by two observers and significant stenosis was defined as >=50%. FFR <=0.8 indicated functionally significant stenoses. RESULTS: M320-CCTA had 94% sensitivity and 94% negative predictive value (NPV) for FFR <=0.8. Overall accuracy was 70%, specificity 54% and positive predictive value 65%. On receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for CCTA to predict FFR <=0.8 was 0.74 which was comparable with ICA. The absence of a significant stenosis on M320-CCTA was associated with a 6% revascularisation rate. M320-CCTA predicted revascularisation with an AUC of 0.71 which was comparable with ICA. CONCLUSIONS: M320-CCTA has excellent sensitivity and NPV for functional stenoses and therefore may act as an effective gatekeeper to defer ICA and revascularisation. Like ICA, M320-CCTA lacks specificity for functional stenoses and only has moderate accuracy to predict the need for revascularisation. KEY POINTS: * Important information about the heart is provided by 320-row multidetector CT coronary angiography (M320-CCTA). * M320 CCTA accurately detects and excludes functional stenoses determined by fractional flow reserve (FFR). * Non-significant stenoses on M320-CCTA associated with fewer cardiac events and less revascularisation. * M320-CCTA may act as a gatekeeper for invasive angiography and inappropriate revascularisation. * Like ICA, M320 CCTA only has moderate accuracy to predict vessels requiring revascularisation. PMID- 24217644 TI - Role of aquaporin-5 in gallbladder carcinoma. AB - BACKGROUND/PURPOSE: Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. METHODS: AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene(r)). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. RESULTS: Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC50 of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). CONCLUSIONS: Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC. PMID- 24217645 TI - Trypanosoma brucei aquaglyceroporins facilitate the uptake of arsenite and antimonite in a pH dependent way. AB - BACKGROUND: Trypanosoma brucei is a primitive parasitic protozoan that thrives in diverse environments such as the midgut of the tsetse fly and the blood of a mammalian host. For an adequate adaptation to these environments, the parasite's aquaglyceroporins play an important role. METHODS AND RESULTS: In order to test their ability to transport trivalent arsenic and antimony, we expressed the three known Trypanosoma brucei aquaglyceroporins (TbAQPs) in the heterologous systems of yeast null aquaporin mutant and Xenopus laevis oocytes. For both expression systems, we found a pH dependent intracellular accumulation of As(III) or Sb(III) mediated by all of the three TbAQPs, with the exception of TbAQP1-As(III) uptake. Additionally, we observed that Trypanosoma brucei aquaglyceroporins allow the passage of As(III) in both directions. CONCLUSION: Taken together, these results demonstrated that T. brucei aquaglyceroporins can serve as entry routes for As(III) and Sb(III) into the parasitic cell, and that this uptake is pH sensitive. Therefore, aquaporins of protozoan parasites may be considered useful as a vehicle for drug delivery. PMID- 24217646 TI - EGF positively regulates the proliferation and migration, and negatively regulates the myofibroblast differentiation of periodontal ligament-derived endothelial progenitor cells through MEK/ERK- and JNK-dependent signals. AB - BACKGROUND/AIMS: Remodeling of fibrous and vascular tissues in the periodontal ligament (PDL) around the tooth root was observed during tooth movement by orthodontic force application. We previously demonstrated that a single cell derived culture (SCDC) of primarily cultured PDL fibroblasts, called SCDC2, has an endothelial progenitor cell (EPC)-like character and can form endothelial cell (EC) marker-positive blood vessel-like structures. However, the types of molecular mechanisms that control the in vivo kinetic properties and the differentiation of the PDL-derived EPC-like cells into myofibroblasts (MFs), which are known to expand fibrous tissues, require clarification. METHODS: Using specific mitogen activated protein kinase (MAPK) inhibitors, we examined how epidermal growth factor (EGF)-mediated MAPK signals affected the proliferation, migration, and MF differentiation of these cells. RESULTS: EGF induced SCDC2 cell proliferation in MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)- and c-Jun N-terminal kinase (JNK)-dependent manners. In addition, EGF suppressed the expression of MF differentiation markers in these cells in a MEK/ERK dependent manner, and, moreover, stimulated the cell migration in a MEK/ERK dependent manner. CONCLUSION: EGF regulates fibrous tissue remodeling in PDLs through MEK/ERK- and JNK-mediated signals by affecting the proliferation, migration, and MF differentiation of the PDL-derived EPC-like cells. PMID- 24217647 TI - Periodic mechanical stress stimulates the FAK mitogenic signal in rat chondrocytes through ERK1/2 activity. AB - BACKGROUND/AIMS: The biological effects of periodic mechanical stress on chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying chondrocyte mechanosensing and signaling in response to periodic mechanical stress remain to be determined. In the current study, we examined the effects of focal adhesion kinase (FAK) signaling on periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. METHODS AND RESULTS: Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr(397) and Tyr(576/577). Reduction of FAK with targeted shRNA via transfection of NH2-terminal tyrosine phosphorylation deficient FAK mutant Y397F or Y576F-Y577F abolished periodic mechanical stress induced chondrocyte proliferation and matrix synthesis, accompanied by attenuated ERK1/2 phosphorylation. However, activation of Src, PLCgamma1 and Rac1 was not prevented upon FAK suppression. Furthermore, pretreatment with the Src-selective inhibitor, PP2, and shRNA targeted to Src or suppression of Rac1 with its selective inhibitor, NSC23766, blocked FAK phosphorylation at Tyr,(576/577) but not Tyr,(397) under periodic mechanical stress. Interestingly, FAK phosphorylation neither at Tyr(397) nor at Tyr(576/577) was affected by PLCgamma1 depletion when periodic mechanical stress was applied. In addition, Tyr(397) and Tyr(576/577) phosphorylation levels were reduced upon pretreatment with a blocking antibody against integrin beta1 under conditions of periodic mechanical stress. CONCLUSION: Our findings collectively suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through at least two pathways, integrin beta1-Src-Rac1-FAK(Tyr(576/577))-ERK1/2 and integrin beta1 FAK (Tyr(397))-ERK1/2. PMID- 24217648 TI - Doxorubicin caused apoptosis of mesenchymal stem cells via p38, JNK and p53 pathway. AB - BACKGROUND/AIMS: Doxorubicin is a widely used chemotherapeutic agent, but its clinical use is restricted because of a high risk of cardiotoxicity. Bone marrow derived mesenchymal stem cells (BMSCs) may repair ischaemically damaged myocardium through transdifferentiation and paracrine action. The aim of this study is to investigate if doxorubicin causes the apoptosis of BMSCs and in turn impairs its healing ability. METHODS: BMSCs were exposed to doxorubicin, and cell apoptosis was determined by western blot and stainings. RESULTS: Doxorubicin reduced the survival ratio and caused the apoptosis of BMSCs, with the increase of intracellular ROS level and depolarization of mitochondrial membrane potential. The ROS scavenger NAC abrogated these consequences. Moreover, doxorubicin markedly activated phosphorylated ERK, p38 and JNK proteins in BMSCs. The specific inhibitors for p38 (SB203580) and JNK (SP600125) may abolish doxorubicin-induced apoptosis of BMSCs but the specific ERK inhibitor (PD98059) not, indicating p38 and JNK activation contribute to BMSCs apoptosis. Also, the phosphorylated and total p53 proteins were increased in doxorubicin-treated BMSCs. Proapoptotic cleaved caspases-3 was upregulated and antiapoptotic Bcl-2 protein was reduced in doxorubicin-treated BMSCs. At last, ELISA assay showed that doxorubicin treatment reduced the VEGF and IGF-1 released by BMSCs. CONCLUSION: Taken together, doxorubicin caused BMSCs apoptosis associated with p38, JNK and p53 pathways. PMID- 24217649 TI - The E-F hand calcium-binding protein S100A4 regulates the proliferation, survival and differentiation potential of human osteosarcoma cells. AB - BACKGROUND/AIMS: Osteosarcoma (OS) is the most common primary bone malignancy in children and young adults. Molecular mechanisms underlying the pathogenesis of OS remain to be fully understood. Several members of the E-F hand calcium-binding S100 protein family are differentially expressed in human cancers. We previously showed that S100A6 is highly expressed in OS tumors. In this study, we investigated the role of S100A4 in regulating OS proliferation and osteogenic differentiation. METHODS/RESULTS: Endogenous S100 expression was examined by semi quantitative PCR in human OS lines. Adenoviral vector-mediated overexpression and RNAi knockdown of S100A4 were used to assess S100A4's effects on cell proliferation, migration and invasion and osteogenic differentiation. Apoptosis was assessed by using anti-caspase-3 immunostaining and flow cytometry with annexin V staining. Early osteogenic marker alkaline phosphatase (ALP) and late markers osteocalcin (OCN) and osteopontin (OPN) were assessed to determine the status of osteogenic differentiation. We found that S100A4 was elevated in metastatic MG63.2 cells. S100A4 knockdown inhibited cell proliferation, prolonged cell doubling time, and induced significant apoptosis. Silencing S100A4 expression in OS cells delayed cell wounding closure and diminished the numbers of migrated OS cells in transwell invasion assay. Furthermore, silencing S100A4 expression stimulated ALP activity, as well as late markers OPN and OCN, in both OS cells and mesenchymal stem cells. CONCLUSION: Our results strongly suggest that S100A4 may promote OS tumor growth by regulating the cell cycle, reducing apoptosis, and inhibiting osteogenic differentiation. Thus, S100A4 may serve as a marker for tumorigenic potential, as well as a therapeutic target. PMID- 24217650 TI - Toll-like receptor-2 ligand peptidoglycan upregulates expression and ubiquitin ligase activity of CHIP through JNK pathway. AB - BACKGROUND: Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70) interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP. METHODS/RESULTS: In this study, we showed that PGN significantly up-regulated the expression of CHIP in both mRNA and protein levels in RAW264.7 cells in a time dependant manner, and the expression of CHIP induced by PGN was abolished in TLR2 knockout macrophages. No significant change in CHIP was observed after lipopolysaccharide (LPS, TLR4 agonist) and cytosine-phosphorous-guanine oligonucleotide (CpG ODN, TLR9 agonist) treatment. Moreover, PGN markedly induced the expression and activity of CHIP in macrophages, whereas this effect was attenuated by SP600125, a selective inhibitor of JNK. CONCLUSION: Our study for the first time demonstrates that TLR2 activation enhances the expression and activity of CHIP through JNK signaling pathway. PMID- 24217651 TI - Tannic acid induced suicidal erythrocyte death. AB - BACKGROUND: The polyphenol tannic acid with antioxidant and antimicrobial potency may trigger suicidal death of nucleated cells or apoptosis and thus may counteract tumor growth. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with appearance of phosphatidylserine at the erythrocyte surface. A major trigger of eryptosis is increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). Erythrocytes could be sensitized to the eryptotic effect of cytosolic Ca(2+) by ceramide. METHODS: Cell volume has been estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from annexin V binding, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3 fuorescence and ceramide utilizing fluorescent antibodies. RESULTS: A 48 h treatment with tannic acid was followed by significant decrease of forward scatter (>= 1 ug/ml) and significant increase of annexin-V-binding (>= 10 ug/ml). Tannic acid did not significantly modify [Ca(2+)]i (up to 50 uM) but significantly increased ceramide formation (50 uM). The annexin-V-binding following tannic acid treatment (50 uM) was significantly blunted in the nominal absence of extracellular Ca(2+). CONCLUSIONS: Tannic acid stimulates eryptosis, an effect at least partially due to ceramide formation with subsequent sensitization of erythrocytes to cytosolic Ca(2+). PMID- 24217652 TI - Downregulation of clusterin expression in human testicular seminoma. AB - BACKGROUND: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. METHODS: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR) was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. RESULTS: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification). Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. CONCLUSION: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer. PMID- 24217654 TI - alpha-globin gene quadruplication and heterozygous beta-thalassemia: a not so rare cause of thalassemia intermedia. PMID- 24217655 TI - Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target? AB - Psoriasis is a common chronic inflammatory disease of the skin. Its pathogenesis has not been completely elucidated. Phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway has been identified as a key signaling pathway for important cellular functions. The data collected in this review suggest that overexpression of the PI3K/Akt/mTOR pathway may play an important role in the pathogenesis of psoriasis by mediating the immune pathogenesis, the epidermal hyperplasia or/and the angiogenesis in the disease. Advances in understanding the pathogenesis of psoriasis has provided new insight into potential therapeutic targets, including the development of biological therapies, resulting in remarkable clinical responses in patients with severe psoriasis. More recently, small molecule oral preparations targeting intracellular signaling that may prove effective have been developed. Data suggest that PI3K/Akt/mTOR pathway may be a potential target for treatment of psoriasis. PMID- 24217657 TI - Air embolism in the internal jugular vein. PMID- 24217659 TI - "Are you sure it's about 'age'?". PMID- 24217660 TI - Mdm2 SNP309 G-variant is associated with invasive growth of human urinary bladder cancer. AB - OBJECTIVE: Human mouse double minute 2 (Mdm2) is essential in degrading p53 by acting as an ubiquitin ligase and therefore plays a vital role in cell cycle and survival. The G-variant of the Mdm2 SNP309, which is located within the promoter of the Mdm2 gene, increases expression of Mdm2 and thereby inhibits the p53 pathway. Several studies have investigated the influence of this SNP on disease risk and onset of various malignancies. The impact of Mdm2 SNP309 on bladder cancer is still to be established due to inconsistent data. METHODS: In a case control study we determined the distribution of Mdm2 SNP309 genotypes in 111 patients with an early-onset bladder cancer (diagnosis <45 years of age), in 113 consecutive bladder cancer patients and in a control group consisting of 140 patients without any malignancy. RESULTS: There was no significant association between the allelic distribution of the Mdm2 SNP309 and tumor risk, early onset, gender or grade of the tumor. According to tumor stage we found a significant difference in the distribution of the Mdm2 SNP309 between patients with noninvasive and invasive (>=pT1) tumor growth (p = 0.016). In patients with invasive tumors a significant increase of the G allele was found (T/T vs. T/G + G/G; p = 0.023; OR 2.203, 95% CI 1.111-4.369). CONCLUSION: These data indicate that the G-variant of the Mdm2 SNP309 might influence the development of a more aggressive tumor phenotype in patients with bladder cancer without affecting the overall tumor risk. PMID- 24217662 TI - Association between the ultrasonographic and clinical findings in the hips of patients with juvenile idiopathic arthritis. AB - OBJECTIVE: To describe the ultrasonographic (US) findings in the hips of patients with juvenile idiopathic arthritis (JIA) and the association between these findings and the signs, symptoms, and activity of the disease. MATERIALS AND METHODS: The present retrospective study included 92 patients with JIA. The disease subtypes, age at disease onset, length of disease progression, disease activity, and clinical manifestations of the hip pathology were assessed. US examinations were routinely performed, and the images were analysed by two ultrasonographers who were blinded to the patients' clinical conditions. RESULTS: Of the 92 patients included in the study, 69.6% were girls, and the average age was 12.4 +/- 5.1 years. Thirty-three (35.9%) participants exhibited the persistent oligoarticular subtype, and 30 (32.6%) exhibited the rheumatoid factor (RF)-negative polyarticular subtype. Forty-four participants exhibited signs and/or symptoms of hip pathology. Twenty-nine (31.5%) participants exhibited abnormal US findings, and 34.4% exhibited subclinical synovitis. The US alterations exhibited an association with subclinical synovitis in 34.4% of the cases. The US alterations bore a correlation with the presence of hip-related signs and/ or symptoms (P = 0.021), particularly joint limitations (P = 0.006), but were not correlated with the disease activity (P = 0.948) or subtype (P = 0.108). Clinical synovitis was associated with polyarticular involvement (P = 0.002) and disease activity (P = 0.017). Subclinical synovitis was not correlated with the investigated variables. CONCLUSION: Clinical affection of the hip in JIA, particularly joint limitation, is associated with synovitis (revealed by US assessment) independently of the activity and subtype of the disease. Therefore, healthcare professionals should consider the possible occurrence of silent disease and subclinical synovitis, which might contribute to hip deterioration. PMID- 24217663 TI - Psychiatric symptoms in patients with systemic lupus erythematosus: frequency and association with disease activity using the Adult Psychiatric Morbidity Questionnaire. AB - INTRODUCTION: While the neurolupus criteria are well-established, global psychiatric manifestations are of variable frequency in patients with systemic lupus erythematosus (SLE); their relation with disease activity is unknown. OBJECTIVE: To evaluate the frequency of psychiatric symptoms in SLE using the Adult Psychiatric Morbidity Questionnaire (APMQ); to correlate APMQ changes with disease activity and socio-economic variables. MATERIALS AND METHODS: This cross sectional study evaluated patients with active or inactive SLE as to the prevalence of psychiatric symptoms utilizing, for the first time, the APMQ. Eight or more affirmative replies out of 45 questions defined the APMQ as abnormal. Patients were classified according to the American College of Rheumatology 1997 criteria, and disease activity was measured by the SLEDAI. RESULTS: Seventy-two SLE patients entered the study, being 68 females (94.4%). Mean age was 46.1 years (+/- 12 SD). The frequency of abnormal APMQ was of 89%. Out of the 64 SLE patients with altered APMQ, 60 (93.7%) had common mental disorders, mostly anxiety and somatization. There was no correlation of psychiatric symptoms with active disease (rs = 0.09; P = 0.46), or with history of psychosis and/or seizures attributable to SLE (P = 1.00). Psychiatric symptoms also did not correlate with age at disease onset (rs = -0.16) or disease duration (rs = 0.11). There was an association of abnormal APMQ with low education level (P = 0.02), but not with family income allotted to the patient (P = 0.24). CONCLUSION: The frequency of psychiatric symptoms measured by the APMQ was high in our SLE population. An abnormal APMQ was disconnected from SLE activity, but it did associate with low education level. PMID- 24217664 TI - Assessment of enthesopathy in patients with fibromyalgia by using new sonographic enthesitis index. AB - OBJECTIVE: The aim of the present study is to determine the frequency of enthesopathy in fibromyalgia (FM) by using a newly developed ultrasonography (US) method, the Madrid Sonography Enthesitis Index (MASEI). METHODS: This study was conducted on 38 consecutive patients with FM and 48 healthy sex- and age-matched controls. Six entheseal sites (olecranon tuberosity, superior and inferior poles of patella, tibial tuberosity, superior and inferior poles of calcaneus) on both lower limbs were evaluated. All US findings were identified according to MASEI. Scores of patients and controls were compared by Student's t-test and Mann Whitney U-test. Validity was analysed by receiver operating characteristic curve. Values of P < 0.05 were considered significant. RESULTS: Total enthesitis score was 7.39 +/- 4.99 (mean +/- SD) among FM patients and 3.7 +/- 3.22 among healthy controls (P < 0.001). The receiver operating characteristic curve established an ultrasound score of > 3.5 in the FM group as the best cut-off point to differentiate between cases and controls. No statistically significant correlation was found between the MASEI score and the FM disease duration, and the location of the tender points. CONCLUSIONS: Misdiagnoses of FM are harmful to patients and the community, and the presence of enthesopathy among FM patients increases. Its detection with the MASEI score may help to discriminate FM patients presenting with ill-defined symptoms and signs, in order to prevent mistreatment. PMID- 24217665 TI - Association between the rs7700944 polymorphism in the TIM-4 gene and rheumatoid arthritis in Zahedan, southeast Iran. AB - INTRODUCTION: Recently, an association between rheumatoid arthritis (RA) and the rs7700944 G>A variant in the T-cell immunoglobulin and mucin domains 4 (TIM-4) has been reported. OBJECTIVE: The present study aimed at investigating the impact of that polymorphism on susceptibility to RA in a sample of the Iranian population. PATIENTS AND METHODS: This case-control study was conducted on 120 patients with RA and 120 healthy subjects. The rs7700944 polymorphism in the TIM 4 gene was determined using tetra amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) assay. RESULTS: No significant difference was observed regarding the rs7700944 polymorphism of the TIM-4 gene between patients with RA and normal individuals. In females, no significant association was found between the groups concerning the rs7700944 polymorphism of the TIM-4 gene. In males, the GA+AA genotype increased the risk of RA in comparison with the GG genotype (OR = 5.15, 95% CI = 1.30-20.48, P = 0.020). Furthermore the results showed that the rs7700944 A allele increased the risk of RA (OR = 4.39, 95% CI = 1.43-13.54, P = 0.009). CONCLUSION: Our results do not support an association between the rs7700944 polymorphism of the TIM-4 gene and RA. An interaction between this polymorphism and sex suggests a sex-specific association between this single nucleotide polymorphism and RA, which remains to be fully elucidated. PMID- 24217666 TI - Profile of paediatric rheumatology specialists and services in the state of Sao Paulo. AB - INTRODUCTION: Paediatric rheumatology (PR) is an emerging specialty, practised by a limited number of specialists. Currently, there is neither a record of the profile of rheumatology patients being treated in Brazil nor data on the training of qualified rheumatology professionals in the country. OBJECTIVE: To investigate the profile of PR specialists and services, as well as the characteristics of paediatric patients with rheumatic diseases, for estimating the current state of rheumatology in the state of Sao Paulo. PATIENTS AND METHODS: In 2010, the scientific department of PR of the Paediatric Society of Sao Paulo administered a questionnaire that was answered by 24/31 accredited specialists in PR practising in state of Sao Paulo and by 8/21 institutions that provide PR care. RESULTS: Most (91%) of the surveyed professionals practise in public institutions. Private clinics (28.6%) and public institutions (37.5%) reported not having access to nailfold capillaroscopy, and 50% of the private clinics reported not having access to acupuncture. The average duration of professional practise in PR was 9.4 years, and 67% of the physicians had attended postgraduate programmes. Seven (87.5%) public institutions perform teaching activities, in which new paediatric rheumatologists are trained, and five (62.5%) offer postgraduate programmes. Two thirds of the surveyed specialists use immunosuppressants and biological agents classified as "restricted use" by the Health Secretariat. The disease most frequently reported was juvenile idiopathic arthritis (29.1-34.5%), followed by juvenile systemic lupus erythematosus (JSLE) (11.6-12.3%) and rheumatic fever (9.1-15.9%). The incidence of vasculitis (including Henoch-Schonlein purpura, Wegener's granulomatosis, and Takayasu's arteritis) and autoinflammatory syndromes was higher in public institutions compared to other institutions (P = 0.03, P = 0.04, P = 0.002, and P < 0.0001, respectively). Patients with JSLE had the highest mortality rate (68% of deaths), mainly due to infection. CONCLUSION: The field of PR in the state of Sao Paulo has a significant number of specialists with postgraduate degrees who mostly practise at teaching institutions with infrastructures appropriate for the care of high-complexity patients. PMID- 24217667 TI - [Anti-synthetase syndrome: anti-PL-7, anti-PL-12 and anti-EJ]. AB - OBJECTIVES: Due to the scarcity of studies in the literature, we conducted an analysis of a series of patients with the anti-PL-7, PL-12 and EJ types of antisynthetase syndrome (ASS). METHODS: We conducted a retrospective cohort study of 20 patients with ASS (8 with anti-PL-7, 6 with PL-12, 6 with EJ) monitored in our department between 1982 and 2012. RESULTS: The mean patient age at disease onset was 38.5 +/- 12.9 years, and the disease duration was 4.5 +/- 6.4 years. Of all the patients, 70% were white and 85% were female. Constitutional symptoms occurred in 90% of cases. All patients presented objective muscle weakness in the limbs; in addition, 30% were bedridden and 65% demonstrated high dysphagia at diagnosis. Joint and pulmonary involvement and Raynaud's phenomenon occurred in 50%, 40% and 65% of cases, respectively, with more than half of the patients presenting incipient pneumopathy, ground-glass opacity and/or pulmonary fibrosis. There were no cases of neurological and/or cardiac involvement. All patients received prednisone or other immunosuppressants depending on tolerance, side effects and/or disease refractoriness. Importantly, patients with the anti-EJ type of ASS demonstrated higher rates of recurrence. Two patients died during follow-up, and 1 patient had breast cancer at the time of diagnosis. CONCLUSIONS: ASS (anti-PL-7, PL-12 and EJ) was found to predominantly affect white women. Although the autoantibodies described in the present study are more related to pulmonary than joint involvement, our patients showed a significant percentage of both types of involvement and a high percentage of myopathy. We also observed a low mortality rate. PMID- 24217668 TI - Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus. AB - The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE. PMID- 24217669 TI - Testicular vasculitis: a rare manifestation of rheumatoid arthritis. AB - Testicular vasculitis is a very rare extra-articular manifestation of rheumatoid arthritis (RA). We describe the case of a 53-year-old man diagnosed with RA for eight years, who was poorly controlled and developed rheumatoid vasculitis, which manifested as leg ulcers and peripheral polyneuropathy. The patient also had acute neutrophilic meningitis and was treated with antibiotics and intravenous pulse therapy with methylprednisolone (500 mg daily) for three days, followed by oral cyclophosphamide (2 mg/kg daily) and prednisone. Overall improvement was observed, and the patient was discharged. But 15 days later, the meningitis recurred, and the patient was readmitted and treated again with antibiotics. Three days later, he developed pain and enlargement of his left testicle with gangrene. Unilateral orchiectomy was performed, revealing lymphocytic vasculitis. The patient died two days later due to aspiration pneumonia. This case illustrates a rare and severe manifestation of rheumatoid vasculitis. PMID- 24217670 TI - Camptocormia secondary to polymyositis. AB - Camptocormia is a postural affliction characterised by abnormal flexion of the thoracolumbar spine, which appears upon standing, increases with walking, and disappears in the supine position. Only five cases of camptocormia secondary to idiopathic inflammatory myopathies have been described in the literature. In this case report, we describe the case of a male patient 67 years of age who suffered from polymyositis for 18 years, which was associated with manifestations compatible with camptocormia. The clinical manifestations were stable and did not progress. Polymyositis is an idiopathic inflammatory myopathy clinically characterised by symmetric weakness that predominantly affects the proximal muscles. Nevertheless, polymyositis is a systemic autoimmune disease; therefore, the skeletal muscles may be diffusely affected, including the paravertebral muscles, which may manifest as camptocormia. PMID- 24217671 TI - Lipid profile in adult patients with idiopathic juvenile arthritis. AB - The inflammatory processes in the joints of a child with juvenile idiopathic arthritis (JIA) can persist into adulthood. Inflammation has been linked to distortions of the lipid profile and accelerated atherogenesis. In the present study, we examined the lipid profiles of adults with JIA compared with those of healthy people. A lipid profile of a sample of 54 adults with JIA (57.3% with polyarticular JIA, 37.0% with oligoarticular JIA, 1.9% with enthesitis-related JIA and 3.7% with systemic onset JIA) and 54 healthy subjects were compared. In the adults with JIA, data on gender, age, age at disease onset, the presence of rheumatoid factor (RF) and antinuclear antibodies (ANA), a Health Assessment Questionnaire (HAQ) and the disease duration were collected. We found that hypercholesterolaemia, increased low-density lipoprotein (LDL) and decreased high density lipoprotein (HDL) were more common in patients with JIA than the controls (P = 0.016, P < 0.0001 and P = 0.0008, respectively). Changes in the levels of total cholesterol (TC) and LDL were more common in the individuals who had a later onset of disease (P = 0.0017 for TC and P = 0.023 for LDL). In the entire JIA group, no other variable, such as RF, ANA, disease duration or responses to the HAQ, could be linked to dyslipidaemia (P = non-significant). We concluded that the adult patients with JIA have a lipid profile with increased TC and LDL levels and decreased levels of HDL compared to the controls. No clinical feature could be correlated with this change except for the age at disease onset. PMID- 24217672 TI - Thyroid function testing in patients with newly diagnosed hyperlipidemia. PMID- 24217674 TI - Kidney cancer: Low serum sodium linked to poor outcomes for patients with mRCC treated with targeted therapy. PMID- 24217675 TI - Prostate cancer: Biopsy--it's stressful! PMID- 24217676 TI - Kidney cancer: Axitinib destined for second place? PMID- 24217677 TI - Prostate cancer: IMRT treatment rates increase with urologist self-referral. PMID- 24217679 TI - Prostate cancer: Age is nothing but a number. PMID- 24217678 TI - Contemporary diagnostic work-up of testicular germ cell tumours. AB - Diagnostic work-up of testicular masses should begin with a complete patient history and palpation of the testes with both hands. First-line imaging of the scrotum should be performed using multiparametric ultrasonography, that is the sequential use of grey-scale ultrasonography, colour Doppler ultrasonography (CDUS), and, if available, contrast-enhanced ultrasonography (CEUS) and real-time elastography (RTE). Increased vascularization--a characteristic of malignancy and inflammation--is visualized on CDUS and CEUS. RTE provides additional information for distinguishing between benign and malignant tissue by measuring tissue elasticity of lesions. MRI is another powerful modality, typically used for second-line imaging of intrascrotal disorders. MRI can provide images with a broad field of view of the scrotal contents. Cancerous lesions are identified on MRI by their signal enhancement after injection of contrast agent. Testicular germ cell tumours require treatment by inguinal orchiectomy. Testis-sparing surgery is advocated for benign tumours and in solitary testicles provided the tumour is <3 cm and the preoperative serum testosterone level is normal. For intraoperative decision-making with regard to testis-sparing surgery, frozen section histological examination can be used, which has a false-negative rate of <10%. PMID- 24217680 TI - Amine formylation via carbon dioxide recycling catalyzed by a simple and efficient heterogeneous palladium catalyst. AB - A simple and efficient Pd/Al2O3-NR-RD catalyst was prepared by depositing palladium on a shape controllable Al2O3-NR support through a two-step process that involves hydrothermal synthesis of Al2O3-NRs followed by reductive deposition of palladium. This catalyst showed high activity in the catalytic formylation of amines by CO2-H2 under mild conditions with up to 96% yield. PMID- 24217681 TI - A cholinergic trigger drives learning-induced plasticity at hippocampal synapses. AB - Learning induces plastic changes in synapses. However, the regulatory molecules that orchestrate learning-induced synaptic changes are largely unknown. Although it is well established that cholinergic inputs from the medial septum modulate learning and memory, evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. Here we find that the activation of muscarinic acetylcholine (ACh) receptors (mAChRs) mediates the contextual fear learning driven strengthening of hippocampal excitatory pyramidal synapses through the synaptic incorporation of AMPA-type glutamate receptors (AMPARs). Contextual fear learning also enhances the strength of inhibitory synapses on hippocampal pyramidal CA1 neurons, in a manner mediated by the activation of, not mAChRs, but, nicotinic AChRs (nAChRs). We observe a significant correlation between the learning-induced increases in excitatory and inhibitory synaptic strength at individual pyramidal neurons. Understanding the mechanisms underlying cholinergic regulation of learning-induced hippocampal synaptic plasticity may help the development of new therapies for cognitive disorders. PMID- 24217683 TI - Evaluation of articular eminence pneumatization using cone beam computed tomography. AB - AIM: Knowledge about the anatomy of the temporomandibular joint (TMJ) and its surrounding structures is mandatory for success in surgical interventions and for understanding the pathway of spread of infections in this region. This study aims to investigate the anatomy and morphology of pneumatized articular eminence (PAT) using cone beam computed tomography (CBCT) imaging in a group of patients. METHODS: A retrospective study on 825 patients (377 males, 448 females) aged between 18 and 91 years was performed using sagittal and coronal CBCT images. PAT was defined as non-expansile, nondestructive cyst-like radiolucency in the zygomatic process of the temporal bone, which appears similar to the mastoid air cells. It was classified in two groups as unilocular and multilocular. Statistical comparison of gender, age and localization was performed using chi square test and correspondence analysis. P<0.05 was considered as significant. RESULTS: Twenty-eight pneumatized articular eminence were found in 21 patients, representing a prevalence of 2.54%. Patients with PAT had a mean age of 28.9 years with a range of 21-78 years. Ten cases (47.6%) occurred in females and 11 cases (52.4%) occurred in males. The results of statistical tests showed no significant differences among the groups with respect to gender, age, and localization (P>0.05). CONCLUSION: Pneumatization of the articular eminence is a challenging entity for TMJ surgery and spread of infections in this region. Practitioners who are dealing with TMJ surgery and pathology should have detailed information about this anatomical variation since it may cause serious complications. PMID- 24217682 TI - Calcimimetics increase CaSR expression and reduce mineralization in vascular smooth muscle cells: mechanisms of action. AB - AIMS: Vascular calcification (VC) contributes to morbidity and mortality in patients with chronic kidney disease (CKD). Allosteric modulators of the calcium (Ca)-sensing receptor (CaSR) may slow the progression of VC in CKD patients either by reducing serum parathyroid hormone (PTH), Ca, and phosphate levels or by a direct effect on the vessel wall. The aim of this study was to examine the effects of calcimimetics on CaSR expression, cell phenotype, and mineral deposition in human vascular smooth muscle cells (h-VSMCs). METHODS AND RESULTS: Primary h-VSMCs were exposed for 14 days to increasing concentrations of Ca(2+) (from 1.8 to 5 mmol/L) in the presence or absence of calcimimetics R-568 or AMG 641 (0.1 MUmol/L). Mineralization was detected by Alizarin red staining, and the cell phenotype was assessed using immunocytochemistry and qRT-PCR. CaSR expression was evaluated using flow cytometry. Short- and long-term exposure (1 day to 14 days) of h-VSMCs to calcimimetics promoted CaSR protein transport from the endoplasmic reticulum to the plasma membrane with enhanced CaSR expression on the cell surface, together with an increase in total cell CaSR expression due to enhanced biosynthesis. In pro-mineralizing conditions, exposure to calcimimetics counteracted the Ca(2+)-dependent reduction of CaSR expression, decreased matrix collagen secretion, and mineral deposition by ~90%. These effects involved CaSR activation since it could be inhibited by CaSR siRNA, but not scrambled siRNA. CONCLUSIONS: The calcimimetic-dependent increase in biosynthesis and activation of the CaSR in h-VSMCs probably play a key role in the protection against calcium induced VC. PMID- 24217684 TI - Conscious sedation with diazepam and midazolam for dental patient: priority to diazepam. AB - AIM: The aim of this paper was to determine whether the use of midazolam is a better technique than the use of diazepam, in relation with the definition of conscious sedation in dentistry. METHODS: Eighty-eight patients undergoing oral surgery were divided into 2 groups in which the sedation was randomly achieved with equipotent cumulative doses of diazepam and midazolam, up to a maximum dose of 8 and 4 mg respectively. Patient's tranquillity was assessed after every dose, using a visual analogue score to ten points and the sedation was evaluated as mild, moderate or deep. Blood pressure, heart rate and SpO2 were also recorded. Psychomotor conditions, by Newman test, and the incidence of amnesia and the patient's satisfaction, by telephone interview, were both evaluated. RESULTS: The number of patients who reached maximum subjective tranquillity was greater already after the third dose of diazepam. The average scores of tranquillity were higher after diazepam. Patients treated with diazepam experienced a higher incidence of mild sedation, patients treated with midazolam a higher incidence of moderate and deep sedation. In patients treated with midazolam blood pressure, heart rate and SpO2 were lower. Postoperative recovery was similar in the 2 groups. After midazolam patients experienced greater amnesia for local anesthesia and drowsiness. Satisfaction was high with both treatments. CONCLUSION: The study shows that sedation with diazepam is more in line with the definition of conscious sedation in dentistry. Diazepam guarantees the persistence of consciousness and maximum subjective tranquillity levels. The recovery and satisfaction were comparable in the 2 groups. PMID- 24217685 TI - Odontostomatological aspects in patients with Goldenhar syndrome: a series of 9 patients. AB - The authors observed and followed nine patients with Goldenhar syndrome to identify the variability and severity malformations mainly affecting the orofacial district, but also other systems. Considering the severity of the lesions and the affected organs and tissues, the authors report preventive and therapeutic approaches, which present considerable difficulties in timing and quality of interventions. PMID- 24217686 TI - Extensive rhabdomyoma of the head and neck region: a case report and a literature review. AB - Rhabdomyomas are rare mesenchymal benign tumors of striated muscle origin that can be classified into cardiac and extracardiac types. Cardiac rhabdomyomas are considered as hamartomatous lesion because of their association with phacomatosis. Extracardiac type is further classified into adult, fetal and genital form, depending on the individual tumor's degree of differentiation. Adult head and neck rhabdomyomas are rare pathologies of adult patients, with a male predominance. The occurrence of multifocality is a rare manifestation of this uncommon lesion. Presenting symptoms are related to the location and dimension of the tumors and they include upper airway obstruction, Eustachian tube dysfunction, dysphagia and mucosal and neck mass. Because of their high rate of recurrence, radical resection is the treatment of choice of this kind of tumors. In this article is reported a rare and particularly large case of head and neck adult rhabdomyoma, presenting with an history of sleep apnea and night time stridor. PMID- 24217687 TI - Juvenile paradental cyst: presentation of a rare case involving second molar. AB - The aim of this article was to describe a rare case of paradental cyst of the permanent mandibular second molar. A 14-year-old girl was referred to Oral Surgery Department, Dental Clinic, IRCSS Fondazione Ca' Granda, University of Milan, Italy, for the evaluation of the deep probing located on the buccal aspect of her erupted mandibular left second molar. Clinical signs of inflammation were absent and the mucosa around the second molar appeared clinically normal. Pulp tests for the second molar were positive. The evaluation of the panoramic radiograph did not revealed radiolucency. The Cone-beam tomography showed a well defined semilunar-shaped radiolucency demarcated by a fine radiopaque line. The cyst was enucleated. The histopathologic analisys revealed the presence of hyperplastic, non-keratinized squamous epithelium with heavy, dense inflammatory cell infiltrate in the epitelium and connective tissue wall. This analysis associated with macroscopic, clinical and radiografic examination confirmed the diagnosis of paradental cyst. A clinic-pathologic correlation, incorporating the surgical, radiographic and histologic findings, is required to obtain the final diagnosis of paradental cyst. Today, the treatment of choice is simple enucleation and thorough curettage of the cyst without extraction of the involved tooth, but if CT demonstrates erosions in the buccal or lingual cortices, marsupialization should be the treatment of choice. PMID- 24217688 TI - Necrotizing sialometaplasia in an HIV positive cocaine user: a case report. AB - The aim of this paper was to present a case report of a male patient attending a Semiology and Stomatology Clinic with an erythematous ulcerated lesion on his palate. The patient reported that he was HIV positive as well as being addicted to cocaine. After a biopsy and a histopathological exam, he was diagnosed as having necrotizing sialometaplasia. The lesion diminished spontaneously in thirty days after the exam. Correct diagnosis as well as physical and complementary exams are paramount to avoid any incorrect therapy. As drug addiction and HIV infection have both been associated to necrotizing sialometaplasia, as in the present case, it is difficult to establish if the aetiological factor was drug usage or the HIV infection or even, the combination of these two factors. Although considering the influence of HIV infection on the oral health, we may assume that, at least, it favored the onset of this oral lesion. PMID- 24217689 TI - Stoichiometry dependent Co3+ spin-state in LaxSr2-xCoGaO5+delta brownmillerite phases. AB - Phases in the LaxSr2-xCoGaO5+delta (0.5 <= x <= 1) series adopt anion-vacancy ordered brownmillerite-type structures. The x = 0.5 and x = 0.6 phases show only small deviations from the ideal A2B2O5 brownmillerite stoichiometry and exhibit paramagnetic behaviour above 100 K, with magnetic susceptibilities indicative of a high-spin, S = 2 configuration for the Co(3+) centres present. In contrast, lanthanum-rich phases (x >= 0.7) incorporate increasing amounts of 'additional' oxygen and show much smaller paramagnetic susceptibilities, consistent with the Co(3+) centres present adopting low-spin S = 0 spin states. The evolution with lanthanum concentration of both the oxygen stoichiometry and the magnetic susceptibility of phases is rationalised on the basis of the lattice strain which builds across the compositional series. This lattice strain acts to couple the Co(3+) spin state to the oxygen stoichiometry in the range 0.65 < x < 0.85 giving materials oxygen sensing capability. PMID- 24217690 TI - Organocatalyzed stereospecific C-C bond formation of beta-lactams. AB - Herein, we report the development of mild, organocatalyzed routes to novel carbapenam derivatives through aldol, Mannich and Michael C-C bond forming reactions. PMID- 24217691 TI - Genetic factors involved in risk for methamphetamine intake and sensitization. AB - Lines of mice were created by selective breeding for the purpose of identifying genetic mechanisms that influence the magnitude of the selected trait and to explore genetic correlations for additional traits thought to be influenced by shared mechanisms. DNA samples from high and low methamphetamine-drinking (MADR) and high and low methamphetamine-sensitization lines were used for quantitative trait locus (QTL) mapping. Significant additive genetic correlations between the two traits indicated a common genetic influence, and a QTL on chromosome X was detected for both traits, suggesting one source of this commonality. For MADR mice, a QTL on chromosome 10 accounted for more than 50 % of the genetic variance in that trait. Microarray gene expression analyses were performed for three brain regions for methamphetamine-naive MADR line mice: nucleus accumbens, prefrontal cortex, and ventral midbrain. Many of the genes that were differentially expressed between the high and low MADR lines were shared in common across the three brain regions. A gene network highly enriched in transcription factor genes was identified as being relevant to genetically determined differences in methamphetamine intake. When the mu opioid receptor gene (Oprm1), located on chromosome 10 in the QTL region, was added to this top-ranked transcription factor network, it became a hub in the network. These data are consistent with previously published findings of opioid response and intake differences between the MADR lines and suggest that Oprm1, or a gene that impacts activity of the opioid system, plays a role in genetically determined differences in methamphetamine intake. PMID- 24217692 TI - Ceftaroline plus avibactam demonstrates bactericidal activity against pathogenic anaerobic bacteria in a one-compartment in vitro pharmacokinetic/pharmacodynamic model. AB - Anaerobic pathogens are often associated with polymicrobial infections, such as diabetic foot infections. Patients with these infections are often treated with broad-spectrum, multidrug therapies targeting resistant Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus, as well as Gram-negative bacteria and anaerobes. The broad-spectrum, non-beta-lactam, beta-lactamase inhibitor avibactam has been combined with ceftaroline and may provide a single product alternative for complicated polymicrobial infections. We compared the activity of ceftaroline-avibactam (CPA) to that of ertapenem (ERT) against common anaerobic pathogens in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. Simulations of doses of ceftaroline-fosamil at 600 mg every 8 h (q8h) (maximum free drug concentration [fCmax], 17.04 mg/liter, and half-life [t1/2], 2.66 h) plus avibactam at 600 mg q8h (fCmax, 11.72 mg/liter, and t1/2, 1.8 h) and of ertapenem at 1 g q24h (fCmax, 13 mg/liter, and t1/2, 4 h) were evaluated against two strains of Bacteroides fragilis, one strain of Prevotella bivia, and one strain of Finegoldia magna in an anaerobic one-compartment in vitro PK/PD model over 72 h with a starting inoculum of ~8 log10 CFU/ml. Bactericidal activity was defined as a reduction of >=3 log10 CFU/ml from the starting inoculum. Both CPA and ERT were bactericidal against all four strains. CPA demonstrated improved activity against Bacteroides strains compared to that of ERT but had similar activity against Finegoldia magna and P. bivia, although modest regrowth was observed with CPA against P. bivia. No resistance emerged from any of the models. The pharmacokinetics achieved were 92 to 105% of the targets. CPA has potent in vitro activity against common anaerobic pathogens at clinically relevant drug exposures and may be a suitable single product for the management of complicated polymicrobial infections. PMID- 24217693 TI - A high-content phenotypic screen reveals the disruptive potency of quinacrine and 3',4'-dichlorobenzamil on the digestive vacuole of Plasmodium falciparum. AB - Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca(2+). This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3',4'-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs. PMID- 24217694 TI - In vitro pharmacodynamics of human simulated exposures of ceftaroline and daptomycin against MRSA, hVISA, and VISA with and without prior vancomycin exposure. AB - The effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistant Staphylococcus aureus (MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-h in vitro pharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediate S. aureus (hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10 CFU during 96 h from baseline. Control isolates grew to 9.16 +/- 0.32, 9.13 +/- 0.14, and 8.69 +/ 0.28 log10 CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved >=3 log10 CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10 CFU was largest for sequential therapy with vancomycin followed by ceftaroline (-5.22 +/- 1.2, P = 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (-3.60 +/- 0.6, P = 0.037 versus daptomycin), compared with daptomycin (-2.24 +/- 1.0), vancomycin ( 1.40 +/- 1.8), and sequential therapy with vancomycin followed by daptomycin ( 1.32 +/- 1.0, P > 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred. PMID- 24217695 TI - O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis. AB - Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID- 24217697 TI - Population pharmacokinetic modeling of the unbound levofloxacin concentrations in rat plasma and prostate tissue measured by microdialysis. AB - Levofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the infection site. Newer fluoroquinolones show a greater penetration into the prostate. In the present study, we compared the unbound levofloxacin prostate concentrations measured by microdialysis to those in plasma after a 7-mg/kg intravenous bolus dose to Wistar rats. Plasma and dialysate samples were analyzed using a validated high-pressure liquid chromatography-fluorescence method. Both noncompartmental analysis (NCA) and population-based compartmental modeling (NONMEM 6) were performed. Unbound prostate tissue concentrations represented 78% of unbound plasma levels over a period of 12 h by comparing the extent of exposure (unbound AUC0-infinity) of 6.4 and 4.8 h.MUg/ml in plasma and tissue, respectively. A three-compartment model with simultaneous passive diffusion and saturable distribution kinetics from the prostate to the central compartment gave the best results in terms of curve fitting, precision of parameter estimates, and model stability. The following parameter values were estimated by the population model: V1 (0.38 liter; where V1 represents the volume of the central compartment), CL (0.22 liter/h), k12 (2.27 h(-1)), k21 (1.44 h(-1)), k13 (0.69 h(-1)), Vmax (7.19 MUg/h), kM (0.35 MUg/ml), V3/fuprostate (0.05 liter; where fuprostate represents the fraction unbound in the prostate), and k31 (3.67 h(-1)). The interindividual variability values for V1, CL, Vmax, and kM were 21, 37, 42, and 76%, respectively. Our results suggest that levofloxacin is likely to be substrate for efflux transporters in the prostate. PMID- 24217696 TI - Evaluation of PD 404,182 as an anti-HIV and anti-herpes simplex virus microbicide. AB - PD 404,182 (PD) is a synthetic compound that was found to compromise HIV integrity via interaction with a nonenvelope protein viral structural component (A. M. Chamoun et al., Antimicrob. Agents Chemother. 56:672-681, 2012). The present study evaluates the potential of PD as an anti-HIV microbicide and establishes PD's virucidal activity toward another pathogen, herpes simplex virus (HSV). We show that the anti-HIV-1 50% inhibitory concentration (IC50) of PD, when diluted in seminal plasma, is ~1 MUM, similar to the IC50 determined in cell culture growth medium, and that PD retains full anti-HIV-1 activity after incubation in cervical fluid at 37 degrees C for at least 24 h. In addition, PD is nontoxic toward vaginal commensal Lactobacillus species (50% cytotoxic concentration [CC50], >300 MUM), freshly activated human peripheral blood mononuclear cells (CC50, ~200 MUM), and primary CD4(+) T cells, macrophages, and dendritic cells (CC50, >300 MUM). PD also exhibited high stability in pH-adjusted Dulbecco's phosphate-buffered saline with little to no activity loss after 8 weeks at pH 4 and 42 degrees C, indicating suitability for formulation for transportation and storage in developing countries. Finally, for the first time, we show that PD inactivates herpes simplex virus 1 (HSV-1) and HSV-2 at submicromolar concentrations. Due to the prevalence of HSV infection, the ability of PD to inactivate HSV may provide an additional incentive for use as a microbicide. The ability of PD to inactivate both HIV-1 and HSV, combined with its low toxicity and high stability, warrants additional studies for the evaluation of PD's microbicidal candidacy in animals and humans. PMID- 24217698 TI - Population pharmacokinetic and pharmacogenetic analysis of nevirapine in hypersensitive and tolerant HIV-infected patients from Malawi. AB - We modeled nevirapine (NVP) pharmacokinetics in HIV-infected Malawian patients to assess the relationship between drug exposure and patient characteristics, genetic polymorphisms, and development of hypersensitivity reaction (HSR). One thousand one hundred seventeen patients were prospectively recruited and followed for 26 weeks with multiple or single serum samples obtained in a subset of patients for NVP quantification. Single nucleotide polymorphisms (SNPs) within CYP2B6 and CYP3A4 genes were typed. Nonlinear mixed effects modeling was utilized to assess the influence of patient characteristics and host genetics on NVP apparent oral clearance (CL/F) and to explore the relationship between NVP CL/F and HSR. Published haplotype distributions were used to simulate NVP concentrations in Caucasians versus Africans. One hundred eighty patients (101 female) were included in the model; 25 experienced HSR. No associations between patient demographics or HSR and NVP CL/F were evident. A significant relationship between CYP2B6 c.983T>C and CYP2B6 c.516G>T and NVP CL/F was observed (P < 0.01). NVP CL/F was reduced by 23% and 36% in patients with CYP2B6 983TT/516TT and 983TC/516GG or GT, respectively, compared to the reference genotype. Simulated exposures suggested similar proportions (13 to 17%) of patients with subtherapeutic NVP among Caucasians and an African population. Influence of CYP2B6 polymorphisms on NVP CL/F in this population is in agreement with other reports. Our data indicate a lack of association between NVP exposure and HSR. Based on these data, dose optimization based solely on ethnicity (without individual gene testing) is unlikely to impact on risk of treatment failure or toxicity even in an African population with high carriage of poor metabolizer mutations. PMID- 24217699 TI - Urinary concentrations and antibacterial activities of nitroxoline at 250 milligrams versus trimethoprim at 200 milligrams against uropathogens in healthy volunteers. AB - Because of the increasing bacterial resistance of uropathogens against standard antibiotics, such as trimethoprim (TMP), older antimicrobial drugs, such as nitroxoline (NTX), should be reevaluated. This randomized crossover study investigated the urinary concentrations of parent drugs and their metabolites and their antibacterial activities (urinary inhibitory titers [UITs] and urinary bactericidal titers [UBTs]) against uropathogens at three different urinary pH values within 24 h in six healthy volunteers after a single oral dose of NTX at 250 mg versus TMP at 200 mg. In three additional volunteers, urinary bactericidal kinetics (UBK) were studied after oral administration of NTX at 250 mg three times a day. The mean urinary concentrations of NTX and NTX sulfate in 24 h were 0.012 to 0.507 mg/liter and 0.28 to 27.83 mg/liter, respectively. The mean urinary concentrations of TMP were 18.79 to 41.59 mg/liter. The antibacterial activity of NTX was higher in acidic urine than in alkaline urine, and that of TMP was higher in alkaline urine than in acidic urine. The UITs and UBTs of NTX were generally lower than those of TMP except for a TMP-resistant Escherichia coli strain, for which NTX showed higher UITs/UBTs than did TMP. UBK showed mainly bacteriostatic activity of NTX in urine. NTX exhibits mainly bacteriostatic activity and TMP also shows bactericidal activity in urine against susceptible strains. NTX is a more active antibacterial in acidic urine, and TMP is more active in alkaline urine. The cumulative effects of multiple doses or inhibition of bacterial adherence could not be evaluated. (This study has been registered at EudraCT under registration no. 2009-015631-32.). PMID- 24217700 TI - In vitro study of sequential fluconazole and caspofungin treatment against Candida albicans biofilms. AB - Candida albicans biofilms are generally considered to be resistant to azole antifungal agents but susceptible to echinocandins. We demonstrate that in a sequential therapy regimen, treatment with fluconazole first followed by caspofungin leads to a significant decrease of the efficacy of this echinocandin. Cellular stress responses induced by high fluconazole concentrations and mediated by Hsp90 and calcineurin play an important role in this phenomenon. PMID- 24217701 TI - Baseline hepatitis C virus (HCV) NS3 polymorphisms and their impact on treatment response in clinical studies of the HCV NS3 protease inhibitor faldaprevir. AB - A challenge to the treatment of chronic hepatitis C with direct-acting antivirals is the emergence of drug-resistant hepatitis C virus (HCV) variants. HCV with preexisting polymorphisms that are associated with resistance to NS3/4A protease inhibitors have been detected in patients with chronic hepatitis C. We performed a comprehensive pooled analysis from phase 1b and phase 2 clinical studies of the HCV protease inhibitor faldaprevir to assess the population frequency of baseline protease inhibitor resistance-associated NS3 polymorphisms and their impact on response to faldaprevir treatment. A total of 980 baseline NS3 sequences were obtained (543 genotype 1b and 437 genotype 1a sequences). Substitutions associated with faldaprevir resistance (at amino acid positions 155 and 168) were rare (<1% of sequences) and did not compromise treatment response: in a phase 2 study in treatment-naive patients, six patients had faldaprevir resistance associated polymorphisms at baseline, of whom five completed faldaprevir-based treatment and all five achieved a sustained virologic response 24 weeks after the end of treatment (SVR24). Among 13 clinically relevant amino acid positions associated with HCV protease resistance, the greatest heterogeneity was seen at NS3 codons 132 and 170 in genotype 1b, and the most common baseline substitution in genotype 1a was Q80K (99/437 [23%]). The presence of the Q80K variant did not reduce response rates to faldaprevir-based treatment. Across the three phase 2 studies, there was no significant difference in SVR24 rates between patients with genotype 1a Q80K HCV and those without Q80K HCV, whether treatment experienced (17% compared to 26%; P = 0.47) or treatment naive (62% compared to 66%; P = 0.72). PMID- 24217702 TI - Postoperative macular hole formation after vitrectomy with internal limiting membrane peeling for the treatment of epiretinal membrane. AB - PURPOSE: To evaluate the incidence, clinical features, and outcomes of macular hole formation after pars plana vitrectomy with internal limiting membrane peeling for the management of epiretinal membrane. METHODS: Retrospective consecutive chart review of 423 cases. RESULTS: Eleven subjects developed postoperative macular holes (incidence 2.6%; 95% confidence interval, 1.5-4.6%). Two of the 11 subjects developed central macular holes (incidence 0.5%; 95% confidence interval, 0.1-1.7%) while 9 had eccentric (nonfoveal) macular holes (incidence 2.1%; 95% confidence interval, 1.1-4.0%). Seven of the 9 eccentric macular holes were <115 um in diameter, 7 were determined to be along the margin of the internal limiting membrane peel, and 8 were either in the superior or temporal macula. The two central macular holes were closed with subsequent pars plana vitrectomy and gas tamponade. There was no association between macular hole formation and age, gender, preoperative visual acuity, axial length, and preoperative central macular thickness. Overall, a 0.2 or more improvement in logMAR was associated with pseudophakia and poorer preoperative acuity on univariate and multivariate analysis, whereas increased preoperative central macular thickness was associated with improved outcomes on univariate but not multivariate analysis. CONCLUSION: Postoperative macular hole formation is an infrequent sequela to pars plana vitrectomy with internal limiting membrane peeling for epiretinal membrane. In our cohort, eccentric macular holes tended to be small, located along the edge of the internal limiting membrane peel, and were not visually significant. PMID- 24217703 TI - Macular choroidal volume variations in highly myopic eyes with myopic traction maculopathy and choroidal neovascularization. AB - PURPOSE: To compare the choroidal volume (CV) between emmetropic and highly myopic eyes, and to assess if the presence of myopic fundus abnormalities, myopic traction maculopathy, or choroidal neovascularization affects the CV. METHODS: We retrospectively reviewed imaging studies of 98 eyes of 98 patients who underwent CV measurement on optical coherence tomography. We included 31 emmetropic eyes (Group 1), 36 highly myopic eyes without vitreoretinal or choroidal pathologies (Group 2), 21 highly myopic eyes with traction maculopathy (Group 3), and 10 highly myopic eyes with history of choroidal neovascularization (Group 3). Eyes with chorioretinal atrophy were excluded. Regression analysis was performed to evaluate the correlation between CV and multiple variables. RESULTS: Choroidal volume was lower in Group 2 than in Group 1 (P < 0.001), and in Groups 3 and 4 than in Group 2 (P < 0.001 and P = 0.002, respectively). Age (P = 0.002), axial length (P < 0.001), sex (P = 0.047), staphyloma (P < 0.001), and myopic group (P = 0.05) were independent predictors for the final CV (R = 0.645). In highly myopic eyes, CV decreased by 0.32 mm for every 10 years and by 0.49 mm per millimeter of axial length. CONCLUSION: Choroidal thinning is present in highly myopic eyes compared with emmetropic eyes, and is related to age, axial length, sex, and staphyloma. However, myopic eyes with coexisting myopic traction maculopathy or history of choroidal neovascularization have more severe thinning, likely leading to insufficient metabolic supplementation for the macula. PMID- 24217705 TI - Biological variation and reference change values of feline plasma biochemistry analytes. AB - This is the first report concerning biological variation and reference change values of feline plasma biochemistry components in the peer-reviewed literature. Biological variation refers to inherent physiological variation of analytes. The ratio of individual biological variation to group biological variation is referred to as an analyte's index of individuality. This index determines the suitability of an analyte to be assessed in relation to population- or subject based reference intervals. A subject-based reference interval is referred to as a reference change value or critical difference, and is calculated from individual biological variation. Fourteen cats were sampled for plasma biochemistry analysis once weekly for 6 weeks. Samples were stored and then tested at the same time. Results were assessed in duplicate and coefficients of variation for each analyte were isolated to distinguish variation within each subject, between all subjects and by the analyser. From these results, an index of individuality and reference change values were determined for each analyte. Five plasma biochemistry analytes (alkaline phosphatase, alanine aminotransferase, cholesterol, creatinine and globulin) had high individuality and, therefore, subject-based reference intervals are more appropriate; only one analyte (sodium) had low individuality, indicating that population-based reference intervals are appropriate. Most analytes had intermediate individuality so population-based reference intervals should be assessed in relation to subject-based reference intervals. The results of this study demonstrate high individuality for most analytes and, therefore, that population-based reference intervals are of limited utility for most biochemical analytes in cats. PMID- 24217704 TI - Low levels of low-density lipoprotein cholesterol: a negative predictor of survival in elderly patients with advanced heart failure. AB - OBJECTIVES: There are conflicting reports on the role of cholesterol as an adverse prognostic predictor in patients with heart failure (HF). This study aimed to examine the impact of low levels of low-density lipoprotein cholesterol (LDL-c) on cardiac mortality in a cohort of elderly patients with moderate and severe HF. METHODS: Chronic HF patients from the HF Unit at the Tel-Aviv Medical Center (n = 212, 77% males) with an average NYHA classification of 2.8, a mean age of 76.9 +/- 7.3 years (range 66-91) and a mean follow-up of 3.7 years were consecutively enrolled. The cohort was divided into tertiles according to LDL-c levels: LDL <90 mg/dl (group 1), LDL 90-115 mg/dl (group 2) and LDL >115 mg/dl (group 3). RESULTS: The Cox regression analysis revealed that group 3 patients had the best outcome (p = 0.01 vs. groups 2 and 3), with 58% of them surviving longer than 50 months compared to 34% in group 1. The same trend was seen in the group of patients suffering from ischemic cardiomyopathy and in patients who were treated by statins (p = 0.04). CONCLUSION: Low LDL-c levels are associated with a reduced survival in elderly patients with clinically controlled moderate and severe HF. PMID- 24217706 TI - Formulation of a standardized protocol and determination of the size and appearance of the spleen in healthy cats. AB - Standard protocol for splenic measurement is warranted to aid in interpretation when sonographically imaging the spleen of cats. The purpose of this study was to describe the appearance and size of healthy cat spleens, and to develop a standard method of evaluation. Data were obtained from 31 clinically healthy non sedated cats with no sonographic abnormalities. The sonographic appearance of the spleen's relative echogenicity compared to the left renal cortex and the hepatic parenchyma was recorded. Splenic height was measured at three sites. Three measurements were determined at each site, and the mean value of these three measurements was determined and used for data analysis. A significance level of P <0.05 was used for analysis, which was performed using S-PLUS software (version 8.1). The mean proximal height of the spleen was 7.1 mm. The mean body sagittal height was 9.3 mm. The mean height of the tail of the spleen was 8.7 mm (95% confidence interval). The splenic parenchymal echogenicity was less than the left renal cortex echogenicity and greater than the liver in 17/31cats; less than the left kidney cortex and equal to the liver in 5/31cats; equal to the cortex of the left kidney and greater than the liver in 5/31 cats; equal to the liver and renal cortex in 2/31 cats; and less than the liver and kidney with the renal cortex less than the liver in 2/31 cats. The protocol recommended for consistent evaluation of the spleen in the cat includes three specific measurements. PMID- 24217708 TI - Partial parasagittal patellectomy: a novel method for augmenting surgical correction of patellar luxation in four cats. AB - We describe a novel surgical technique used to correct feline patellar luxation (PL) where abnormal patellar tracking persists despite conventional corrective surgery. An anatomical difference between feline and canine stifles is that the feline patella is wider relative to the trochlear sulcus. This results in less constrained patellar tracking. Therefore, patellar subluxation is common in normal cats. It was noticed that in some feline cases with clinically significant PL, PL persisted intraoperatively despite performing the standard corrective procedures. We report a novel surgical technique - partial parasagittal patellectomy - to address the wide shape of the feline patella relative to the sulcus. This technique has been successfully performed in four cats with good outcomes. However, the immediate risks and long-term effects of partial parasaggital patellectomy are not known. We reserve this technique for surgical cases where PL cannot be controlled by conventional means. PMID- 24217707 TI - Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies. AB - Chronic kidney disease (CKD) and degenerative joint disease are both considered common in older cats. Information on the co-prevalence of these two diseases is lacking. This retrospective study was designed to determine the prevalence of CKD in two cohorts of cats: cats randomly selected from four evenly distributed age groups (RS group) and cats recruited for degenerative joint disease studies (DJD group), and to evaluate the concurrence of CKD and DJD in these cohorts. The RS group was randomly selected from four age groups from 6 months to 20 years, and the DJD group comprised cats recruited to four previous DJD studies, with the DJD group excluding cats with a blood urea nitrogen and/or serum creatinine concentration >20% (the upper end of normal) for two studies and cats with CKD stages 3 and 4 for the other two studies. The prevalence of CKD in the RS and DJD groups was higher than expected at 50% and 68.8%, respectively. CKD was common in cats between 1 and 15 years of age, with a similar prevalence of CKD stages 1 and 2 across age groups in both the RS and DJD cats, respectively. We found significant concurrence between CKD and DJD in cats of all ages, indicating the need for increased screening for CKD when selecting DJD treatments. Additionally, this study offers the idea of a relationship and causal commonality between CKD and DJD owing to the striking concurrence across age groups and life stages. PMID- 24217709 TI - Novel avulsion pattern of the left principal bronchus with involvement of the carina and caudal thoracic trachea in a cat. AB - A 2-year-old, 4.5 kg, neutered male domestic shorthair cat was presented to the emergency service with dyspnoea, anorexia and apathetic behaviour. Thoracic radiographs showed typical signs for a thoracic trauma and a tracheal lesion in the region of the carina, consistent with pseudoairway formation. Computed tomography (CT) was performed in the conscious cat to avoid aggravation of air leakage associated with ventilation. The additional CT findings were consistent with a novel pattern of a traumatic avulsion of the left principal bronchus expanding into the carina and caudal thoracic trachea. Despite the complex avulsion pattern, successful treatment was achieved surgically by performing an end-to-end anastomosis via a fifth right intercostal lateral thoracotomy. The cat was ventilated with a feeding tube and jet ventilation throughout. The cat showed excellent recovery 6 months after surgery. PMID- 24217710 TI - Reduction in IL-33 plasma levels might be involved in T cell dysregulation in chronic lymphocytic leukemia. PMID- 24217712 TI - Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling. AB - Chemokine receptor 5 (CCR5) antagonists provide a new therapeutic approach in the treatment of HIV-1 (AIDS). TAK-779 displays high affinity and selectivity for the CCR5 receptor and serves as a lead compound for the development of further antagonists. In order to increase the oral bioavailability replacement of the quaternary ammonium structure by a tertiary amine and modification of the 4 methylphenyl moiety were envisaged. Herein, a new synthetic strategy for the development of TAK-779 analogs by late stage diversification is reported. The Suzuki-Miyaura cross-coupling reactions allowed various modifications of the central amide building block 3 at the end of the synthesis leading to compounds 2f and 2h with a promising CCR5 binding affinity. PMID- 24217714 TI - Efficient organometal trihalide perovskite planar-heterojunction solar cells on flexible polymer substrates. AB - Organometal trihalide perovskite solar cells offer the promise of a low-cost easily manufacturable solar technology, compatible with large-scale low temperature solution processing. Within 1 year of development, solar-to-electric power-conversion efficiencies have risen to over 15%, and further imminent improvements are expected. Here we show that this technology can be successfully made compatible with electron acceptor and donor materials generally used in organic photovoltaics. We demonstrate that a single thin film of the low temperature solution-processed organometal trihalide perovskite absorber CH3NH3PbI3-xClx, sandwiched between organic contacts can exhibit devices with power-conversion efficiency of up to 10% on glass substrates and over 6% on flexible polymer substrates. This work represents an important step forward, as it removes most barriers to adoption of the perovskite technology by the organic photovoltaic community, and can thus utilize the extensive existing knowledge of hybrid interfaces for further device improvements and flexible processing platforms. PMID- 24217713 TI - Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways. AB - Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKE, requires interaction with adapter proteins such as TRAF associated NF-kappaB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKE/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity. PMID- 24217715 TI - Surgical therapy of extensive knee joint empyema: mid-term results after two stage versus one-stage procedures. AB - PURPOSE: Untreated knee joint empyema leads to rapid destruction of the joint and, thus far, has proven challenging to treat. This study presents data obtained after one- versus two-stage surgical approaches. Specifically, clinical outcome, complication rate, re-infection rate, duration of operation, and hospital stay are reported. METHODS: Between 2006 and 2010, 67 patients with extensive knee joint empyema underwent surgical therapy. Patients underwent either a two-stage surgical approach with open joint treatment for 7-10 days or a one-stage procedure with primary closure of the knee joint after radical debridement. RESULTS: The two-stage procedure was performed on 36 patients, whereas the one stage procedure was performed on 31 patients. Infection duration prior to the index procedure ranged from 3 days to 55 months (two-stage: ~5 months, one-stage: ~2.4 months). The groups did not differ significantly in demographic group characteristics. Hospital stay and duration of operation were significantly (p < 0.01) reduced in the one-stage group compared to the two-stage group (31.1 +/- 10.6 vs. 23.4 +/- 14.4 days and 105 +/- 32 vs. 68 +/- 18 min, respectively). Functional outcome improved in both groups from the pre- to post-operative period, but did not differ significantly between groups. CONCLUSION: The one stage open surgical approach produced similar results to the two-stage approach in the treatment of extensive knee joint empyemas. However, by waiving the open joint treatment concept, duration of hospital stay and operation time could be significantly reduced. LEVEL OF EVIDENCE: III. PMID- 24217716 TI - Diagnostic accuracy of clinical tests for sciatic nerve entrapment in the gluteal region. AB - PURPOSE: The purpose of this study was to determine the diagnostic accuracy of the straight leg raise (SLR), active piriformis, and seated piriformis stretch tests in identifying individuals with sciatic nerve entrapment. METHODS: Thirty three individuals (female = 25 and male = 8) with a mean age of 43 years (range 15-64; SD +/- 11 years) were included in the study. Twenty-three subjects had endoscopic findings of sciatic nerve entrapment. Ten subjects without entrapment during endoscopic assessment were used as a control group. The results of the SLR, active piriformis, and seated piriformis stretch tests were retrospectively reviewed for each subject and compared between both groups. The accuracy of these tests for the endoscopic finding of sciatic nerve entrapment was determined by calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. RESULTS: The SLR had sensitivity of 0.15, specificity of 0.95, positive likelihood ratio of 3.20, negative likelihood ratio of 0.90, and diagnostic odds ratio of 3.59. The active piriformis test had sensitivity of 0.78, specificity of 0.80, positive likelihood ratio of 3.90, negative likelihood ratio of 0.27, and diagnostic odds ratio of 14.40. The seated piriformis stretch test had sensitivity of 0.52, specificity of 0.90, positive likelihood ratio of 5.22, negative likelihood ratio of 0.53, and diagnostic odds ratio of 9.82. The most accurate findings were obtained when the results of the active piriformis test and seated piriformis stretch test were combined, with sensitivity of 0.91, specificity of 0.80, positive likelihood ratio of 4.57, negative likelihood ratio of 0.11, and diagnostic odds ratio of 42.00. CONCLUSIONS: The active piriformis and seated piriformis stretch tests can be used to help identify patients with and without sciatic nerve entrapment in the deep gluteal region. PMID- 24217717 TI - Influence of tibial slope asymmetry on femoral rotation in patients with lateral patellar instability. PMID- 24217719 TI - Myocardial infarction and ischemic heart disease in overweight and obesity with and without metabolic syndrome. AB - IMPORTANCE: Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. OBJECTIVE: To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD. DESIGN, SETTING, AND PARTICIPANTS: We examined 71,527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. RESULTS: During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1.81-3.00) in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Normal weight vs overweight vs obesity and presence vs absence of metabolic syndrome did not interact on risk of MI or IHD (P = .90 and P = .44). Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals (log-rank trend P = .006 to P < .001). Although the multivariable adjusted hazard ratio for MI in individuals with vs without metabolic syndrome was 1.54 (95% CI, 1.32-1.81) across all BMI categories, addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41). CONCLUSIONS AND RELEVANCE: These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that metabolic syndrome is no more valuable than BMI in identifying individuals at risk. PMID- 24217718 TI - Regional mechanical properties of human patellar tendon allografts. AB - PURPOSE: Very little is known regarding regional biomechanical properties of patellar tendon allografts. METHODS: Ten human bone-tendon-bone (BTB) patellar grafts were separated into equal thirds and underwent cyclic and failure testing. Grafts were non-irradiated and processed using proprietary sterilization methods. RESULTS: The central third was the thickest region (4.9 +/- 0.4 mm) compared to the medial and lateral (p < 0.05). The lateral third was the longest region (58.8 +/- 8.8 mm) compared to the medial (47.9 +/- 8.5 mm) and central (47.2 +/- 8.8 mm) portions (p < 0.05). Cyclic testing demonstrated no regional differences with respect to elongation (n.s.) and creep strain (n.s.). Failure testing demonstrated increased maximum load and stiffness in the central region (1,680 +/ 418 N and 278 +/- 67 N/mm, respectively) as compared to the medial (1,033 +/- 214 N, p < 0.002, 201 +/- 37 N/mm, p < 0.03) and lateral thirds (908 +/- 412 N, p < 0.03, 173 +/- 66 N/mm, p < 0.002). Elongation at maximum load did not vary between regions. Central region maximum stress (41.0 +/- 12.5 MPa) was greater than that of the medial third (28.1 +/- 3.6 MPa, p < 0.02), with strain at maximum stress larger in the central third (0.21 +/- 0.03) compared to lateral (0.16 +/- 0.03, p < 0.01). CONCLUSIONS: The central third of a non-irradiated, human bone-patellar tendon-bone construct is thicker and biomechanically superior to the medial and lateral regions in most respects. These findings reinforce the use of the central third of a patellar tendon allograft in anterior cruciate ligament reconstruction. Further investigations are required to determine whether the decreased biomechanical properties of the medial and lateral third of the BTB construct negatively influence the mechanical function of hemi-BTB grafts. PMID- 24217720 TI - Two applications of solid phantoms in performance assessment of optical coherence tomography systems. AB - Virtual tissues (phantoms) are widely used for performance evaluation of imaging systems. Specific design of the phantom is necessary for the correct assessment of a system's parameters. In an effort to reduce the amount of time and energy spent making application-oriented phantoms, we describe procedures to make epoxy resin solid phantoms based on Mie scattering theory, with two different scatterers: polystyrene and gold microspheres. The phantoms are specifically designed to be used in two applications: (a) the gold microspheres solid phantoms are used to estimate the point-spread function (PSF) of an optical coherence tomography (OCT) system, and (b) the polystyrene solid phantom are used to evaluate the performance of an OCT-images optical properties extraction (OPE) algorithm. Phantoms with differing combination of materials have been tested to achieve the most suitable combination for producing an accurate PSF for application (a) and a valid evaluation/parameter optimization of the algorithm in application (b). An en face time-domain dynamic focus OCT is used for imaging. PMID- 24217721 TI - Modeling of intensity-modulated continuous-wave laser absorption spectrometer systems for atmospheric CO(2) column measurements. AB - The focus of this study is to model and validate the performance of intensity modulated continuous-wave (IM-CW) CO(2) laser absorption spectrometer (LAS) systems and their CO(2) column measurements from airborne and satellite platforms. The model accounts for all fundamental physics of the instruments and their related CO(2) measurement environments, and the modeling results are presented statistically from simulation ensembles that include noise sources and uncertainties related to the LAS instruments and the measurement environments. The characteristics of simulated LAS systems are based on existing technologies and their implementation in existing systems. The modeled instruments are specifically assumed to be IM-CW LAS systems such as the Exelis' airborne multifunctional fiber laser lidar (MFLL) operating in the 1.57 MUm CO(2) absorption band. Atmospheric effects due to variations in CO(2), solar radiation, and thin clouds, are also included in the model. Model results are shown to agree well with LAS atmospheric CO(2) measurement performance. For example, the relative bias errors of both MFLL simulated and measured CO(2) differential optical depths were found to agree to within a few tenths of a percent when compared to the in situ observations from the flight of 3 August 2011 over Railroad Valley (RRV), Nevada, during the summer 2011 flight campaign. In addition, the horizontal variations in the model CO(2) differential optical depths were also found to be consistent with those from MFLL measurements. In general, the modeled and measured signal-to-noise ratios (SNRs) of the CO(2) column differential optical depths (taud) agreed to within about 30%. Model simulations of a spaceborne IM-CW LAS system in a 390 km dawn/dusk orbit for CO(2) column measurements showed that with a total of 42 W of transmitted power for one offline and two different sideline channels (placed at different locations on the side of the CO(2) absorption line), the accuracy of the taud measurements for surfaces similar to the playa of RRV, Nevada, will be better than 0.1% for 10 s averages. For other types of surfaces such as low-reflectivity snow and ice surfaces, the precision and bias errors will be within 0.23% and 0.1%, respectively. Including thin clouds with optical depths up to 1, the SNR of the taud measurements with 0.1 s integration period for surfaces similar to the playa of RRV, Nevada, will be greater than 94 and 65 for sideline positions placed +3 and +10 pm, respectively, from the CO(2) line center at 1571.112 nm. The CO(2) column bias errors introduced by the thin clouds are <=0.1% for cloud optical depth <=0.4, but they could reach ~0.5% for more optically thick clouds with optical depths up to 1. When the cloud and surface altitudes and scattering amplitudes are obtained from matched filter analysis, the cloud bias errors can be further reduced. These results indicate that the IM-CW LAS instrument approach when implemented in a dawn/dusk orbit can make accurate CO(2) column measurements from space with preferential weighting across the mid to lower troposphere in support of a future ASCENDS mission. PMID- 24217722 TI - Optimal achromatic wave retarders using two birefringent wave plates: comment. AB - In a recent publication, J. L. Vilas et al. [Appl. Opt.52, 1892 (2013)] described a combined system comprising two wave plates and proposed an expression for the overall retardation. However, to the best of my knowledge, the proposed theoretical expression for the total retardation is incorrect. The authors improperly derived that expression by simply diagonalizating the Jones matrix of the cascaded system. The mistakes are pointed out and discussed in these comments. PMID- 24217723 TI - Optimal achromatic wave retarders using two birefringent wave plates: reply. AB - This reply attempts to cast some more light on the achromatic systems composed by wave plates, in particular to the calculus of the overall retardation and the use of the Jones matrix equivalence theorem. An equivalent expression for the overall retardation of the system in terms of the trace is also given. PMID- 24217724 TI - Spectroscopic observation of neutral carbon during photodissociation of explosive related compounds in the vapor phase. AB - We perform time-resolved laser-induced fluorescence measurements of mononitrotoluenes (MNTs) and dinitrotoluenes (DNTs) in nitrogen and air. We observe the multipeak emission spectrum of NO and find that the emission peak intensity in the 247-248 nm range is stronger than expected compared to the other NO emission peak intensities. This increased emission intensity is believed to be due to neutral carbon [C(I)], which has a strong emission peak at 247.85 nm. By comparing the ratios of integrated emission peak intensities with those expected from the Franck-Condon factors for NO, we are able to identify samples that exhibit C(I) emission. We show that the DNTs exhibit C(I) emission for gate delays of 1500 ns and beyond, while the MNTs exhibit C(I) emission for gate delays of only up to about 500 ns. Carbon deposits in the analysis chamber confirm the presence of C. Ambient NO in air enhances the observed NO+C(I) signal from MNTs and DNTs. PMID- 24217725 TI - Optimal fringe angle selection for digital fringe projection technique. AB - Existing digital fringe projection (DFP) systems mainly use either horizontal or vertical fringe patterns for three-dimensional shape measurement. This paper reveals that these two fringe directions are usually not optimal where the phase change is the largest to a given depth variation. We propose a novel and efficient method to determine the optimal fringe angle by projecting a set of horizontal and vertical fringe patterns onto a step-height object and by further analyzing two resultant phase maps. Experiments demonstrate the existence of the optimal angle and the success of the proposed optimal angle determination method. PMID- 24217726 TI - Design and optimization of the sine condition test for measuring misaligned optical systems. AB - By taking a new look at an old concept, we have shown in our previous work how the Abbe sine condition can be used to measure linearly field-dependent aberrations in order to verify the alignment of optical systems. In this paper, we expand on this method and discuss the design choices involved in implementing the sine condition test (SCTest). Specifically, we discuss the two illumination options for the test: point source with a grating or flat-panel display, and we discuss the tradeoffs of the two approaches. Additionally, experimental results are shown using a flat-panel display to measure linearly field-dependent aberrations. Last, we elaborate on how to implement the SCTest on more complex optical systems, such as a three-mirror anastigmat and a double Gauss imaging lens system. PMID- 24217727 TI - Direct investigation and accurate control of phase profile in liquid-crystal optical-phased array for beam steering. AB - An experimental setup and simple method were proposed to investigate and control the actual phase profile in a high-spatial-resolution liquid-crystal optical phased array (LCOPA). A crossed polarizer and high-resolution microscope objective were employed to transform the light distribution out of the liquid crystal layer into a polarization-interference pattern in which the phase-profile information was wrapped. The polarization-interference pattern was then directly translated into the actual phase profile. Based on this setup, a method was developed to accurately control the actual phase profile, and the steering efficiency at the steering angle of 16 mrad was increased from 80% to 90%. The proposed method also helps in increasing the steering efficiency when disclination lines appear. PMID- 24217728 TI - Measuring rough optical surfaces using scanning long-wave optical test system. 1. Principle and implementation. AB - Current metrology tools have limitations when measuring rough aspherical surfaces with 1-2 MUm root mean square roughness; thus, the surface cannot be shaped accurately by grinding. To improve the accuracy of grinding, the scanning long wave optical test system (SLOTS) has been developed to measure rough aspherical surfaces quickly and accurately with high spatial resolution and low cost. It is a long-wave infrared deflectometry device consisting of a heated metal ribbon and an uncooled thermal imaging camera. A slope repeatability of 13.6 MUrad and a root-mean-square surface accuracy of 31 nm have been achieved in the measurements of two 4 inch spherical surfaces. The shape of a rough surface ground with 44 MUm grits was also measured, and the result matches that from a laser tracker measurement. With further calibration, SLOTS promises to provide robust guidance through the grinding of aspherics. PMID- 24217729 TI - Watt-level passively Q-switched double-cladding fiber laser based on graphene oxide saturable absorber. AB - A watt-level passively Q-switched ytterbium-doped double-cladding fiber laser with a graphene oxide (GO) absorber was demonstrated. The structure of the GO saturable absorber mirror (GO-SAM) was of the sandwich type. A maximum output power of 1.8 W was obtained around a wavelength of 1044 nm. To the best of our knowledge, this is the highest output power in Q-switched fiber lasers based on a GO saturable absorber. The pure GO was protected from the oxygen in the air so that the damage threshold of the GO-SAM was effectively raised. The gain fiber was a D-shaped ytterbium-doped double-cladding fiber. The pulse repetition rates were tuned from 120 to 215 kHz with pump powers from 3.89 to 7.8 W. The maximum pulse energy was 8.37 MUJ at a pulse width of 1.7 MUs. PMID- 24217730 TI - Polarization-induced fluorescence modulation in a self-assembled coordination cage-shaped complex. AB - Polarization-induced fluorescence modulation behavior of a self-assembled coordination cage-shaped complex was investigated using femtosecond laser pulses. The variations of the total two-photon-induced fluorescence (TPF) intensity were found to be strongly modulated by different polarized incident lights and tightly dependent on the linearly polarized component of the excited light. The polarization-induced modulation efficiency of the TPF underwent intensity dependent decrease, which could be attributed to the two-photon-induced excited state absorption. The nonlinear absorption behavior of the complex was also studied by performing both femtosecond open aperture Z-scan and nonlinear transmission measurements, which help to better understand the intrinsic optical properties of the molecule and portend its practical applications. PMID- 24217731 TI - Grouping design of eight-mirror projection objective for high-numerical aperture EUV lithography. AB - A grouping design method for all-sphere initial design of an eight-mirror projection objective is proposed for extreme ultraviolet lithography (EUVL). By separating the eight-mirror objective into three mirror groups (the object side group, the image side group, the middle group), this method allows designers to calculate the parameters of an eight-mirror objective by the nonobstruction constraints and the conjugation relationships of object image and pupils. Exhaustive paraxial search for the middle group is implemented while a designer chosen combination of object side group and image side group is considered. The grouping design process is visualized and steerable. The load of calculation is well controlled in a practical acceptable span. The final eight-mirror design optimized with aspheric parameters achieves an 0.4 numerical aperture on the image side, and the image resolution achieves a diffraction limit with almost no distortion. PMID- 24217732 TI - Multipass cell based on confocal mirrors for sensitive broadband laser spectroscopy in the near infrared. AB - We report on broadband absorption spectroscopy in the near IR using a multipass cell design based on highly reflecting mirrors in a confocal arrangement having the particular aim of achieving long optical paths. We demonstrate a path length of 314 m in a cell consisting of two sets of highly reflecting mirrors with identical focal length, spaced 0.5 m apart. The multipass cell covers this path length in a relatively small volume of 1.25 l with the light beam sampling the whole volume. In a first application, the absorption spectra of the greenhouse gases CO(2), CH(4), and CO were measured. In these measurements we used a femtosecond fiber laser with a broadband spectral range spanning the near IR from 1.5 to 1.7 MUm. The absorption spectra show a high signal-to-noise ratio, from which we derive a sensitivity limit of 6 ppmv for methane observed in a mixture with air. PMID- 24217733 TI - Passive depth estimation using chromatic aberration and a depth from defocus approach. AB - In this paper, we propose a new method for passive depth estimation based on the combination of a camera with longitudinal chromatic aberration and an original depth from defocus (DFD) algorithm. Indeed a chromatic lens, combined with an RGB sensor, produces three images with spectrally variable in-focus planes, which eases the task of depth extraction with DFD. We first propose an original DFD algorithm dedicated to color images having spectrally varying defocus blurs. Then we describe the design of a prototype chromatic camera so as to evaluate experimentally the effectiveness of the proposed approach for depth estimation. We provide comparisons with results of an active ranging sensor and real indoor/outdoor scene reconstructions. PMID- 24217734 TI - Spectral-domain low-coherence interferometry for phase-sensitive measurement of Faraday rotation at multiple depths. AB - We describe a method for differential phase measurement of Faraday rotation from multiple depth locations simultaneously. A polarization-maintaining fiber-based spectral-domain interferometer that utilizes a low-coherent light source and a single camera is developed. Light decorrelated by the orthogonal channels of the fiber is launched on a sample as two oppositely polarized circular states. These states reflect from sample surfaces and interfere with the corresponding states of the reference arm. A custom spectrometer, which is designed to simplify camera alignment, separates the orthogonal channels and records the interference-related oscillations on both spectra. Inverse Fourier transform of the spectral oscillations in k-space yields complex depth profiles, whose amplitudes and phase difference are related to reflectivity and Faraday rotation within the sample, respectively. Information along a full depth profile is produced at the camera speed without performing an axial scan for a multisurface sample. System sensitivity for the Faraday rotation measurement is 0.86 min of arc. Verdet constants of clear liquids and turbid media are measured at 687 nm. PMID- 24217735 TI - Effect of including intraband phenomena in the semiconductor optical amplifier model for propagation of short pulses. AB - A comparison has been done between the two cases when intraband effects are included and when they are excluded in the semiconductor optical amplifier model for propagating short pulses. The numerical investigation shows that the dependence of output pulse chirping and broadening on the amplifier gain, input pulse energy, and input pulsewidth becomes stronger on inclusion of intraband effects. To prove the experimental fact of pulsewidth dependency of the amplifier saturated gain for short pulses, it is compulsory to include intraband effects in the model. We prescribe here an expression for the saturation energy as a function of pulsewidth that correctly predicts the variation obtained numerically. PMID- 24217736 TI - Experimental validation of the six-port design for a highly uniform integrating sphere photometer. AB - We present experimental realization and validation of the six-port design of integrating sphere photometers for total luminous flux measurement, which significantly improves the uniformity of spatial response compared to the conventional single-port design. Construction, measurement procedure, and data acquisition of the realized instrument with a radius of 1 m are described. Measurement of the spatial response distribution function confirms the expected effect of improving the uniformity by averaging the signals from the six detection ports. The related spatial mismatch error is determined to be less than 1.4% for all the realistic cases of beam angles and directions of a test lamp mounted in the vicinity of the sphere center. As a result, we confirm that the realized six-port instrument allows us to eliminate the complicated spatial mismatch correction procedure by adding a relative standard uncertainty of only 1.4/3%~0.81%, which offers a great practical benefit for testing solid-state lighting products of various beam characteristics. PMID- 24217737 TI - Method of mitigation laser-damage growth on fused silica surface. AB - A reliable method, combining femtosecond (fs) laser mitigation and chemical (HF) etching, has been developed to mitigate laser-damage growth sites on a fused silica surface. A rectangular mitigation site was fabricated by an fs laser with a raster scan procedure; HF etching was then used to remove the redeposition material. The results show that the mitigation site exhibits good physical qualities with a smooth bottom and edge. The damage test results show that the growth threshold of the mitigation sites increases. Furthermore, the structural characteristic of samples was measured by a photoluminescence (PL) spectrometer, and the light intensification caused by damage and mitigation sites was numerically modeled by the finite-difference time-domain (FDTD). It revealed that the removal of damaged material and structure optimization contribute to the increase of the damage growth threshold of the mitigation site. PMID- 24217738 TI - Measurement of the phase shift between intensity and frequency modulations within DFB-LD and its influences on PGC demodulation in a fiber-optic sensor system. AB - The parameters of the semiconductor laser source are vital for the performances of optical coherent systems. In this paper, a novel method to measure the phase shift phim between laser central optical-frequency modulation (COFM) and the accompanied optical-intensity modulation (AOIM) is proposed, which is easy to realize and requires no further fiber etalons or high-speed demodulators. An orthogonal test is utilized to measure phim. Experimental results show that the value of phim approaches 1.09pi under different COFM conditions. Then the interference model of phase-generated carrier (PGC) demodulation is modified by taking into account the effect of phim, and the influences of phim on the demodulation results using two methods (look-up table and AOIM-factor division) are further analyzed in detail. PMID- 24217739 TI - Ultrabroadband spectral beam combiner spanning over three octaves. AB - We report the design, build, and test of a multispectral laser beam combining collimator with a spectral range in excess of three octaves. The device is based on a sapphire wedge prism, calcium fluoride, and sapphire collimating doublet lens and fiber optic inputs and is designed to operate from ultraviolet (355 nm) to mid-infrared (4075 nm) wavelengths. Five laser sources at different wavelengths were used to validate the concept. The device produced full-angle beam divergence of between 0.1 and 0.2 mrad from 355 to 1908 nm. The bore-sight error with respect to the design wavelength of 1064 nm was 0.07 mrad for 532 nm, 0.14 mrad for 355 and 1908 nm, and 2.4 mrad for 4075 nm. The results presented here represent, to the authors' knowledge, the widest spectral range of a laser beam combiner yet demonstrated. PMID- 24217740 TI - Computational study of a label-free biosensor based on a photonic crystal nanocavity resonator. AB - In this paper, we demonstrate and theoretically investigate a compact two dimensional (2D) photonic crystal biosensor implemented by a waveguide and cavity. Biomaterials such as DNA molecules and proteins trapped inside a hole cause resonant wavelength shifting at the output terminal. The quality factor and sensitivity were obtained at about 4000 and 1.63 nm/fg, respectively. Also, we investigated this structure as a bulk refractive index sensor with a sensitivity of about 165.45 nm/RIU (refractive index units). Then, we modified the structure as a multichannel biosensor. This biosensor has the capability of highly parallel operation because of special architecture that was obtained by lattice shifting of a single hole around the cavity. Each channel had a different resonant cavity wavelength and the filling of analyte in selected holes caused resonant wavelength shifting, independently. Plane wave expansion (PWE) and finite difference time domain (FDTD) methods were used to analyze and compute the sensor characteristics. PMID- 24217741 TI - Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction. AB - PURPOSE: Bladder outflow obstruction (BOO) is common in the elderly and can result in bladder voiding dysfunction (BVD) due to severe bladder muscle damage. The goal of this research was to evaluate the use of adult stem cells for the treatment of BVD due to decreased muscle contractility in a rat model. MATERIALS AND METHODS: Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) were harvested from male Lewis rats and expanded in culture. BOO was induced by tying a suture around the urethra. Six weeks after obstruction, the development of BVD was confirmed by cystometric analysis in conscious rats, histology and molecular investigations. Injection of ADSCs or MPCs into the bladder wall and synchronous deligation was performed 6 weeks after the obstruction. After stem cell treatment, morphological and functional changes were assessed. Age-matched rats and animals without cellular therapy but deligation-only served as controls. RESULTS: Voiding pressures decreased progressively 6 weeks after obstruction with increased bladder capacities. Structural changes of the detrusor muscle occurred during the time of obstruction with an increased connective tissue-to-smooth muscle ratio and decreased SMA/smoothelin expression. After stem-cell injection, improved voiding pressures and voiding volumes were observed together with recovered tissue architecture. RT-PCR and Western blotting showed an up regulation of important contractile proteins. CONCLUSIONS: We established a reliable model for BVD and demonstrated that ADSCs and MPCs can prevent pathophysiological remodelling and provide regenerated bladder tissue and function. PMID- 24217742 TI - A water-soluble near-infrared probe for colorimetric and ratiometric sensing of SO2 derivatives in living cells. AB - A coumarin TCF-based water-soluble near-infrared fluorescent probe was presented, which could be used for the rapid, colorimetric and ratiometric detection of SO2 derivatives with a detection limit of 0.27 nM. Moreover, this probe could successfully image the analyte in living cells. PMID- 24217743 TI - Dietary modification by common brown lemurs (Eulemur fulvus) during seasonal drought conditions in western Madagascar. AB - Primates often modify dietary composition in relation to seasonal changes in food availability or climate conditions. We studied the feeding patterns of a troop of common brown lemurs (Eulemur fulvus), a semi-frugivorous strepsirhine, in a dry forest in northwestern Madagascar. To understand the mechanism of dietary modification, we recorded daily feeding times of diet items during 101 full-day observations over 1 year, and then conducted a linear model analysis to examine the effects of fruiting tree density in the forest, daily ambient temperature, and weekly rainfall (index of water retained in the forest) on the lemurs' daily feeding time. The lemurs spent dramatically more time on leaf-eating as well as total feeding time, and less time on fruit-eating during the late dry season (total 152 min/day, frugivory 56 min/day, folivory 77 min/day), as compared with other seasons when the diet was highly frugivorous (total 96 min/day, frugivory 81 min/day, folivory 8 min/day). Folivory increased as temperatures rose under the condition of low weekly rainfall, whereas frugivory was unrelated to fruiting tree density. Most (97.4%) diurnal folivory during the late dry season was spent consuming Lissochilus rutenbergianus, chewing the succulent leaves and licking the juice. Because the nutritional analysis showed that L. rutenbergianus is rich in water (80.1% of fresh weight) but poor in protein and nonstructural carbohydrates, its increased use was probably for rehydration. We conducted 13 full-night observations, because brown lemurs increase nocturnal activities during the dry season. At nighttime, the lemurs tended to spend more time eating fruit in the late dry season (32 min/night) than in the early dry season (14 min/night), and never consumed L. rutenbergianus. Fruits rich in nonstructural carbohydrates can be energy sources for Eulemur. They likely engaged in additional nocturnal frugivory for energy compensation. Brown lemurs have a flexible strategy of modifying their diet and feeding activities to cope with environmental stresses. PMID- 24217744 TI - Purulent discharge from the nipples: a quiz. Zuska's disease. PMID- 24217745 TI - Systematization of nursing care and social responsibility in professional practice settings. PMID- 24217746 TI - [Validation of nursing diagnosis: challenges and alternatives]. AB - Studies on validation of nursing diagnoses have been strongly influenced by the methodological framework developed in the 1980s. The suitability of these models to validate elements that make a nursing diagnosis has undergone several criticisms. This article aims to discuss these limitations and describe alternative approaches to overcome the criticism of traditional models. A critical analysis based on recent published literature on new approaches in research diagnoses was taken as basis for the discussions presented. Alternative methods are described for the concept analysis applied the procedures for validation of nursing diagnoses; methods for diagnostic content analysis by proficient judges, and methods for clinical validation of indicators and etiological factors. Conclude that there are few studies with these new approaches and the complexity of the analysis is an aspect that hinders its implementation. PMID- 24217747 TI - [Neonatal nursing: the meaning of existential caring in intensive care unit]. AB - Understanding that care to preterm infants goes through the various steps that are sometimes intertwined in the predominant routine in neonatal intensive care units, requires that the professionals understand the subtleties that hold between caring in the sense of activities and procedures performed in day-to-day, and caring in the existential sense of being and caring for others. This study, in a Heideggerian phenomenological approach, aimed to reveal the existential sense of caring for mothers of premature babies admitted to Neonatal Intensive Care Units. After approval by the Research Ethics Committee, it was conducted interviews with nine mothers. The analysis by the Heideggerian method unveiled that the being-mother, while being-with-the-son, also feel cared for by professionals who provide that faces this existential moment in a safer manner. PMID- 24217748 TI - [The non-nutritive sucking of premature newborn as a nursing technology]. AB - This is an experimental study with a quantitative approach, whose goal was to demonstrate that non-nutritive sucking is effective in pain management during installation, by the nursing staff, of nasal CPAP in preterm infants; and to demonstrate that the use of non-nutritive sucking, concomitantly with the installation of nasal CPAP can be considered a nursing technology. The target population consisted of 20 preterm infants undergoing installation or reinstallation of this artifact, totaling 30 procedures. The newborns were divided randomly into two groups, control and experimental, in which non nutritive sucking was offered, the same do not happening with the control group. The reactions of pain were measured by the scale of NIPS. In 100% of the procedures that occurred concomitant with non-nutritive sucking, newborns did not feel pain; and 100% of the newborns showed pain when such suction was not offered. We conclude that the procedure can be classified as a technology of nursing care. PMID- 24217749 TI - [Evaluation of growth and development of institutionalized children]. AB - The study aimed to evaluate the growth and development of institutionalized children from 0-6 years old. It had a descriptive, transversal and quantitative approach, and was held in a shelter from the Bureau of Labor and Social Development of the Government of the State of Ceara, in the months of March and April 2011. The sample comprised 44 children. It the sample prevailed male children (59.1%), aged 24 to 72 months (56.8%) and with time of sheltering more than one year (72.7%). It was found that the children were in the normal range of nutrition; however, 65.9% of children did not achieve at least one of the development milestones proposed by the Ministry of Health. The study suggests a reflection on how children living in shelters are being assisted by the health team, making it necessary follow up their growth and development, in order to intervene on the alterations. PMID- 24217750 TI - [Fragility of the social network of families of children with chronic disease]. AB - Chronic disease in childhood affects the family social relations. The social network can contribute for a better coping by giving support. This work aims to analyze the fragilities of the social network of families in this condition. It is a qualitative study conducted in a public hospital of Paraiba, from April to June 2011, using genogram, ecomap and semi-structured interview with seven family members of children with chronic disease. The thematic analysis of the results helped to characterize the network and understand the social interactions in the course of the disease and the types of support received. The empirical category (dis)articulation of the social network and the modifications in family routine was built in this process and pointed the diversity of the social network composition, emphasizing that the social support provided by the network is significant, however, not always continuous and suitable with the needs of the families. PMID- 24217751 TI - [Changes in scholar's behavior and development through the family care]. AB - This study aimed to describe the contributions of nursing in the family relationships of scholars who have changes in school behavior and performance. It's an action research, based on the questioning method, using the Arc Method, implemented in five stages: reality observation, key-points, theory, possible solutions, and application to reality. The research happened in a municipal school, located in the west of Santa Maria-RS. 25 scholars' families participated in the sample, during March to May of 2012. It was noticed that the dream of having an ideal family exists, but the lived reality is still permeated by a lot of difficulties and require modifications. Thus, take care of the family relationships shows up as a possibility of society to develop worthily, considering the powerful influence it has on the people character development and formation. PMID- 24217752 TI - [Validation of nursing interventions for patients with spinal cord injury and impaired physical mobility]. AB - This is a descriptive study that aimed to validate the nursing interventions proposed in the Nursing Interventions Classification for the diagnosis of Impaired physical mobility in adults with sequels of spinal cord injury, based on opinions of experts in rehabilitation about each intervention proposed. The sample consisted of 54 nurses who were asked about how they consider the interventions for the nursing diagnosis. A questionnaire was administered to nurses who work at the Sarah Network of Rehabilitation Hospitals. Among the 46 interventions studied, 17 (37%) were considered essential and should be implemented; others 15 (32.6%) were considered complementary, and 14 (30.4%) should not be used and could be discarded. Nursing interventions not described in the classification and suggested by 22 nurses (40.7%) were: Care with Orthoses: Maintenance; and Care with Orthoses: Prevention. PMID- 24217753 TI - [Evaluation of ear acupressure on painful shoulder syndrome: case study]. AB - The Painful Shoulder Syndrome (PSS) is defined as pain and functional limitation resulting from impairment of static and dynamic structures of the shoulder, such as ligaments, capsule and muscles. It is one of the most common and disabling of the musculoskeletal system in the general population with prevalence estimated between 15-25%. This study aimed to evaluate the results of auricular acupressure when used as therapy in the treatment of chronic pain secondary to SOD, and the analgesic effect and therapeutic satisfactory and the estimated time of treatment. To obtain the objective was to perform a case study was to intervene with auricular acupressure beads and crystals as an indicator of the outcome questionnaire Penn Shoulder Score (PSS - Brazil). Data were analyzed qualitatively and quantitatively. We conclude that auriculotherapy is an important therapeutic technique, because the study showed an improvement in the total score of the PSS - Brazil at 34.3%. PMID- 24217754 TI - [Use of drugs by elderly in the community: proposal of nursing action]. AB - Objective of this study was to identify the socio demographic profile and drug use in elderly enrolled in a health unit and to propose nursing actions through identification of diagnoses and prescriptions related, focused on the use of drugs, targeted to these elderly. This descriptive study was conducted in a family health unit, in the state of Rio Grande do Sul, Brazil, with 97 elderly. For data collection it was used a structured form. The data were analyzed by descriptive statistics. it was used Risner's model of diagnostic reasoning for the identification of nursing diagnosis. The elderly used 3.46 drugs and 31.86%, five or more. Seven nursing diagnosis were identified. Those diagnoses were present in at least ten elderly for whom prescriptions related were established. The results of this study may assist in achieving effective action for the resident elderly who uses drugs. PMID- 24217755 TI - [Drug use, blood glucose and body mass index in patients with diabetes mellitus]. AB - This research aimed to relate medication use with blood glucose and body mass index in subjects with type 2 diabetes mellitus. It was performed a cross sectional study, between January and July 2009, at the homes of 437 users of 12 health centers in Fortaleza-CE. We administered a survey about blood glucose, body mass index and medication use. Approximately 99% of study subjects with altered glucose classified as not using daily calcium (p = 0.04). Among those with normal blood glucose levels classified as around 93% did not use daily antidepressants / anxiolytics (p = 0.02). Among those with DM 2 normal body mass index, 45.5% were using daily anti-hypertensive ACE-inhibitor class (p = 0.03). Daily use of ACE inhibitor drugs, antidepressants / anxiolytics and calcium was associated with body mass index and glucose, respectively. It is important for nurses to assess body weight and blood glucose in patients with diabetes, particularly those that are under continuous medication. PMID- 24217756 TI - [Factors related to death by the Pandemic Influenza A (H1N1) 2009 in patients treated with oseltamivir]. AB - This study aimed to identify factors related to death in Pandemic Influenza A(H1N1)2009 in patients treated with Oseltamivir. It is an observational and retrospective study, carried out with data of patients who had presented laboratorial diagnosis of the illness. Data were collected from the notification forms of the disease, belonging to a database of the Ministry of Health. Statistical analysis was performed by chi-square, Student t test and logistic regression, considering significant p values <0,05. The highest mortality was observed in patients aged between 20 and 59 years, low schooling, with the presence of comorbidities, not vaccinated, treated late and had more severe symptoms of infection. The identification of risk factors for death reinforces the need for prevention and early care, especially in the presence of factors that increase the clinical severity of disease. PMID- 24217757 TI - [Occupational stress in intensive care nurses who provide direct care to critical patients]. AB - In order to identify the stress level of nurses that provide direct care to critically ill patients, it was carried out a descriptive and exploratory study in five hospitals of the western region of the state of Parana, Brazil, from May 2010 to July 2010. Fifty-eight intensive nurses participated in the study, whose stress level was evaluated according to the Domain D of Bianchi's Stress Scale. Most (65.5%) of them had medium stress levels, The stressors that obtained the highest levels were: facing death (5.6 points); answering emergency calls unit (5.1 points); caring for critically ill patients' or talking to family members of critically ill patients (both 4.8 points). It is needed to adopt stress prevention and reduction strategies to its minimization or elimination, because the main stressors mentioned are directly related to the duties of nurses. PMID- 24217758 TI - [Social representations of nurses about religiosity while caring for patients in the dying process]. AB - This is a qualitative study, anchored in the Theory of Social Representation and Jodelet thoughts, realized in an Intensive Care and Oncology Unit of a university hospital. The objective was to understand the social representations of nurses on religiosity while caring for dying patients. The data was collected between 2010 May and August, using the technique of Content Analysis of Bardin. The religiosity representations inserted in the caring practice for dying patients, value professional's beliefs about death, its meaning allowing for the development of coping mechanisms. It is considered that the awareness will occur through the understanding of reality and introducing the theme in the discussion of the quality of health and training of professionals. PMID- 24217759 TI - [Matrix support: device for resolution of mental health clinical cases at the primary health care]. AB - The study aimed to comprehend the matrix support as a device to resolution of clinical cases of mental health within the Primary Health Care in a qualitative study, carried out from a case study. The data were collected through observation of matrix practices and analyzed under the view of reflective content analysis. The results pointed out to the following categories: The walking of user: dilemmas and challenges; Sharing of knowledge: an expansion of views? The curtain opens itself: It passed but the pain remains! and RESULTS: collective construction of the therapeutic project. It highlights that matrix practices has the power to sign the paths for the construction of a particular model of health care that is articulate and synergistic with the principles and guidelines of the National Health System. PMID- 24217760 TI - [Perception of nurses about advantages and constraints of their practice in mental health services]. AB - The study aimed to identify the advantages and constraints in the practices of nurses in Mental Health services. A qualitative descriptive study, was conducted in 22 public mental health services in the state of Goias, involving 21 nurses as subjects. The evaluation referential of Avedis Donabedian was used for data discussion. Regarding the facilitating aspects, it were cited the availability of physical resources, furniture and materials for the workshops, professional and interpersonal relationships with staff, and coordination with users. Among the constraining aspects also predominated the structure that is offered by the services. It was evident that the structure and interpersonal relations have been conditioning aspects related to the effectiveness of nurses' practice in mental health services within the state of Goias. PMID- 24217761 TI - [Promotion of nurses to academic management: discussing their role through the theory of adaptation (70's 80's)]. AB - Qualitative research aimed to show the nurses role performed during the management challenge in nursing schools. A retrospective diachronic historical type study was conducted through data collection, critical evaluation and facts presentation based on Roy's adaptation theory. The study reveal that pioneer nurse managers achieved a professional projection inside the university academic scope, based on adaptation, interdependence, by transcending in optimal way between organization members and showing initially a compensatory adaptation level and later on integrated with innovation in the performance of manager's role, based on dialogue, with presence in several scenarios as well as participation in several sectors. PMID- 24217762 TI - [Use of hydrocolloid and calcium alginate in the treatment of skin lesions]. AB - Hydrocolloid and calcium alginate are used to treat cutaneous injuries and many health professionals do not know about its cicatrization effects. This study had the objective to identify the evidences of the action of the hydrocolloid and calcium alginate dressing in the treatment of cutaneous injuries. The method of integrative review was used. 12 studies with evidence levels I, II, III and IV were part of the sample; they were composed by patients with cutaneous injuries treated in any period of time with hydrocolloid dressing or calcium alginate. The evaluated outcomes had been reduction of the area, cicatrization of the injury, rate of cicatrization, time and infection. The results had allowed establishing three recommendations for the use of hydrocolloid and none for use of alginate of calcium in the treatment of chronic injury. PMID- 24217763 TI - [People with pain and intervention needs: systematic literature review]. AB - The study aimed to determine the economic and social impact and that needs of intervention by the health services for persons with pain. It was conducted a search in EBSCO (CINAHL, MEDLINE, British Nursing Index), using the method of PI[C]O and selecting 19 articles of the total of 325 found. The neuropathic pain and the one with musculoskeletal location were identified as the most responsible for health expenditures. The factors positively associated with cost-effective met in the research were: combination of therapeutic regimen with non pharmacological strategies, involvement of multidisciplinary teams specialized in pain management, continuity of care program in community and a telephone line for permanent support. It was concluded that the pain causes significant deterioration in quality of life, with incalculable impact on the performance of the activities of daily living. PMID- 24217764 TI - [Demand-Control model and occupational stress among nursing professionals: integrative review]. AB - The Demand Control model aims to evaluate the occupational stress. This study aimed to know, through an integrative review of the literature, the scientific production about the Demand Control Model to investigation occupational stress among nursing professionals from 2000 to 2011.Of the 16 selected studies, five were published in 2009. Of these studies, 56.25% assessed the Demand and Control dimensions and their correlations with workers' health problems; 37.5% of these studies were related with mental health. The results showed a lack of national publications. We recommend that authors conduct experimental studies to reduce the occupational stress for better conditions of workers' mental health. PMID- 24217765 TI - [International classification of functioning, disability and health: use in nursing care for the elderly]. AB - The objective was to reflect on the International Classification of Functioning, Disability and Health and its use in nursing care for the elderly. It was conducted a brief history of the Classification; it was addressed the functional assessment of the elderly and importance to the proper planning to care actions; and it was showed the applicability of the International Classification of Functioning, Disability and Health by nurses. The classification is able to direct the functional assessment of the elderly, by the nurses, making the integral, realizing this human being as having a body, with needs to perform activities and participation, and belonging to a context /environment. PMID- 24217767 TI - MiR-320a downregulation is associated with imatinib resistance in gastrointestinal stromal tumors. AB - Gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Though imatinib improves the outcome, drug resistance remains the major problem for extending patient survival. Genetic mutation of the drug targets is the known mechanism for imatinib resistance. However, it cannot explain all of the phenomena of imatinib resistance, and numerous additional mechanisms have been proposed to account for imatinib resistance in various model systems. In this study, we applied the SYBR-green quantitative polymerase chain reaction-based array approach to screen the differentially expressed miRNAs between primary GIST patients and imatinib resistant patients. The selected candidate miRNAs were validated in a cohort of 12 GIST patients. We found that low expression of miR-320a was correlated with short time to imatinib resistance, and proposed the potential mechanism of miR 320a for imatinib resistance. PMID- 24217769 TI - Solving the mystery of H7N9 by crystal balls. AB - How the novel influenza H7N9 virus crossed species barrier from avian to human is intriguing. Extrapolation from previous studies on H5N1 can be misleading as illustrated by crystallographic studies on the H7 hemagglutinin with G226L substitution; crystal structure of the neuraminidase N9 showed that R294K substitution interferes with binding to sialic acid or antiviral drugs and reduces viral fitness. PMID- 24217768 TI - Protein post-translational modifications and regulation of pluripotency in human stem cells. AB - Post-translational modifications (PTMs) are known to be essential mechanisms used by eukaryotic cells to diversify their protein functions and dynamically coordinate their signaling networks. Defects in PTMs have been linked to numerous developmental disorders and human diseases, highlighting the importance of PTMs in maintaining normal cellular states. Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), are capable of self-renewal and differentiation into a variety of functional somatic cells; these cells hold a great promise for the advancement of biomedical research and clinical therapy. The mechanisms underlying cellular pluripotency in human cells have been extensively explored in the past decade. In addition to the vast amount of knowledge obtained from the genetic and transcriptional research in hPSCs, there is a rapidly growing interest in the stem cell biology field to examine pluripotency at the protein and PTM level. This review addresses recent progress toward understanding the role of PTMs (glycosylation, phosphorylation, acetylation and methylation) in the regulation of cellular pluripotency. PMID- 24217771 TI - Cell force measurements in 3D microfabricated environments based on compliant cantilevers. AB - We report the fabrication, functionalization and testing of microdevices for cell culture and cell traction force measurements in three-dimensions (3D). The devices are composed of bent cantilevers patterned with cell-adhesive spots not lying on the same plane, and thus suspending cells in 3D. The cantilevers are soft enough to undergo micrometric deflections when cells pull on them, allowing cell forces to be measured by means of optical microscopy. Since individual cantilevers are mechanically independent of each other, cell traction forces are determined directly from cantilever deflections. This proves the potential of these new devices as a tool for the quantification of cell mechanics in a system with well-defined 3D geometry and mechanical properties. PMID- 24217770 TI - Coordinated endothelial nitric oxide synthase activation by translocation and phosphorylation determines flow-induced nitric oxide production in resistance vessels. AB - BACKGROUND/AIMS: Endothelial nitric oxide synthase (eNOS) is associated with caveolin-1 (Cav-1) in plasma membrane. We tested the hypothesis that eNOS activation by shear stress in resistance vessels depends on synchronized phosphorylation, dissociation from Cav-1 and translocation of the membrane-bound enzyme to Golgi and cytosol. METHODS: In isolated, perfused rat arterial mesenteric beds, we evaluated the effect of changes in flow rate (2-10 ml/min) on nitric oxide (NO) production, eNOS phosphorylation at serine 1177, eNOS subcellular distribution and co-immunoprecipitation with Cav-1, in the presence or absence of extracellular Ca(2+). RESULTS: Increases in flow induced a biphasic rise in NO production: a rapid transient phase (3-5-min) that peaked during the first 15 s, followed by a sustained phase, which lasted until the end of stimulation. Concomitantly, flow caused a rapid translocation of eNOS from the microsomal compartment to the cytosol and Golgi, paralleled by an increase in eNOS phosphorylation and a reduction in eNOS-Cav-1 association. Transient NO production, eNOS translocation and dissociation from Cav-1 depended on extracellular Ca(2+), while sustained NO production was abolished by the PI3K-Akt blocker wortmannin. CONCLUSIONS: In intact resistance vessels, changes in flow induce NO production by transient Ca(2+)-dependent eNOS translocation from membrane to intracellular compartments and sustained Ca(2+)-independent PI3K-Akt mediated phosphorylation. PMID- 24217772 TI - Nickel-catalyzed dimerization of pyrrolidinoindoline scaffolds: systematic access to chimonanthines, folicanthines and (+)-WIN 64821. AB - While metal-promoted activation of tertiary alkyl halides often causes elimination and hydrodehalogenation, we have developed a nickel-catalyzed reductive dimerization that allows the generation of a potently reactive tertiary radical equivalent to form a very congested C(sp(3))-C(sp(3)) bond even below room temperature. The catalytic protocol is applicable to the dimerization of several pyrrolidinoindoline scaffolds through an appropriate choice of catalyst to accommodate different substrate reactivities with functional group compatibilities. The efficiency of the nickel-catalyzed protocol was successfully demonstrated through a systematic total synthesis of chimonanthines, folicanthines and (+)-WIN 64821. PMID- 24217778 TI - Gene expression profiling to predict viridans group streptococcal and invasive fungal infection in pediatric acute myeloid leukemia: a brief report from the Children's Oncology Group. PMID- 24217779 TI - MALDI mechanisms: wavelength and matrix dependence of the coupled photophysical and chemical dynamics model. AB - The ultraviolet wavelength and fluence dependence of MALDI ion yields using several matrices has recently been reported (Soltwisch et al., Anal. Chem., 2012, 84, 6567). These extensive data provide a test of the coupled photophysical and chemical dynamics (CPCD) model, and are used to extend the model to new matrices. The experimental phenomena are generally well reproduced by the model, particularly when transient photochemical products or exciplexes are included. While the CPCD is consistent with the data, thermal models appear to be largely incompatible with it. PMID- 24217781 TI - Avoid atrial fibrillation in patients with hypertrophic cardiomyopathy. PMID- 24217780 TI - Everyday discrimination and chronic health conditions among Latinos: the moderating role of socioeconomic position. AB - Emerging research has revealed that everyday discrimination and socioeconomic position may have synergistic effects on the health of racial/ethnic minorities. The present study examined the association between self-reported everyday discrimination and count of chronic health conditions, and explored the moderating role of objective and subjective socioeconomic position on the discrimination-health relation. We utilized nationally representative data of Latino adults (N = 2,554) from the National Latino and Asian American Study. Weighted negative binomial regression modeling was used to estimate the association between self-reported everyday discrimination and count of chronic health conditions, and to test whether this relation was modified by markers of socioeconomic position. Binomial regressions revealed that everyday discrimination was associated with a greater count of chronic conditions. However, moderation analyses indicated that household income moderated the discrimination-health relation, controlling for sociodemographic variables. More specifically, the adverse effects of discrimination were stronger for Latinos in middle-income tertiles compared to their lower income counterparts, such that as frequency of discrimination increased, Latinos with medium levels of household income were predicted to have greater counts of chronic conditions. This was only marginally significant among those in the high-income tertile. Our findings suggest that identifying segments of the Latino population that may be at greatest (and lowest) risk of ill health in the context of perceiving being discriminated against may prove useful for understanding Latino health "paradoxes," and may have implications for tailoring prevention and intervention efforts to particular segments of the Latino population. PMID- 24217782 TI - Is microalbuminuria a risk factor for hypertension in children with solitary kidney? AB - BACKGROUND: The correlations between ambulatory blood pressure measurements (ABPM) and serum cystatin C (Cys C), serum creatinine (Cr), microalbumin (MA), and beta2-microglobulin (beta2-MG) levels in 24 h (24-h) urine were analyzed in children with solitary kidney (SK) and compared to healthy children. METHODS: Fifty children with normal functioning SK and 25 controls were studied. The ABPM, serum Cys C, serum Cr, MA, and beta2-MG levels in 24-h urine were measured in all children. Clinical symptoms and signs, laboratory results, urinary ultrasonography, voiding cystourethrography, and Dimercaptosuccinic acid (DMSA) scintigraphy results were recorded in the SK group. Four patients with Wilms' tumor and two with renal scarring were excluded from the study. RESULTS: The mean ages of the SK group and controls were 9.6 +/- 3.6 and 9.3 +/- 3.3 years, respectively. The serum Cys C and Cr levels, 24-h urinary beta2-MG and MA levels were similar in both groups (p > 0.05). However, 24-h urinary MA excretion was higher in patients living with SK more than 5 years (p = 0.01). Standard deviation scores of ABPM parameters showed no significant correlation with serum Cr, serum Cys C, MA, and beta2-MG in 24-h urine of both groups. CONCLUSIONS: Children with SK have increased 24-h urinary MA excretion in the long term, and need prolonged follow-up to detect early deterioration of renal function and to prevent end-organ damage later in life. PMID- 24217783 TI - The interplay between drugs and the kidney in premature neonates. AB - The kidney plays a central role in the clearance of drugs. However, renal drug handling entails more than glomerular filtration and includes tubular excretion and reabsorption, and intracellular metabolization by cellular enzyme systems, such as the Cytochrome P450 isoenzymes. All these processes show maturation from birth onwards, which is one of the reasons why drug dosing in children is not simply similar to dosing in small adults. As kidney development normally finishes around the 36th week of gestation, being born prematurely will result in even more immature renal drug handling. Environmental effects, such as extra-uterine growth restriction, sepsis, asphyxia, or drug treatments like caffeine, aminoglycosides, or non-steroidal anti-inflammatory drugs, may further hamper drug handling in the kidney. Dosing in preterm neonates is therefore dependent on many factors that need to be taken into account. Drug treatment may significantly hamper postnatal kidney development in preterm neonates, just like renal immaturity has an impact on drug handling. The restricted kidney development results in a lower number of nephrons that may have several long-term sequelae, such as hypertension, albuminuria, and renal failure. This review focuses on the interplay between drugs and the kidney in premature neonates. PMID- 24217784 TI - Lysosome dysfunction in the pathogenesis of kidney diseases. AB - The lysosome, an organelle central to macromolecule degradation and recycling, plays a pivotal role in normal cell processes, ranging from autophagy to redox regulation. Not surprisingly, lysosomes are an integral part of the renal epithelial molecular machinery that facilitates normal renal physiology. Two inherited diseases that manifest as kidney dysfunction are Fabry's disease and cystinosis, each of which is caused by a primary biochemical defect at the lysosome resulting from loss-of-function mutations in genes that encode lysosomal proteins. The functions of the lysosomes in the kidney and how lysosomal dysfunction might contribute to Fabry's disease and cystinosis are discussed. Unlike most other pediatric renal diseases, therapies are available for Fabry's disease and cystinosis, but require early diagnosis. Recent analysis of ceroid neuronal lipofuscinosis type 3 (Cln3) null mice, a mouse model of lysosomal disease that is primarily associated with neurological deficits, revealed renal functional abnormalities. As current and future therapeutics increase the life span of those suffering from diseases like neuronal ceroid lipofuscinosis, it remains a distinct possibility that many more lysosomal disorders that primarily manifest as infant and juvenile neurodegenerative diseases may also include renal disease phenotypes. PMID- 24217785 TI - BMP signaling and its modifiers in kidney development. AB - The kidney develops through mutual interactions between the metanephric mesenchyme and the ureteric bud, the former of which contains nephron progenitors that give rise to glomeruli and renal tubules. Bone morphogenetic protein (BMP) signaling and its modifiers play important roles in many steps of kidney development. BMP4 inhibits ureteric bud attraction, and the BMP antagonist Gremlin is essential for the initial stage of ureteric budding. During mid gestation, BMP7 maintains the nephron progenitors and, at the same time, sensitizes them to the ureteric bud-derived differentiation signal. Crossveinless2 is a pro-BMP factor, and its absence leads to kidney hypoplasia. After birth, when nephron progenitors have disappeared, Dullard, a phosphatase that inactivates BMP receptors, keeps BMP signaling at an appropriate level. Deletion of Dullard results in excessive BMP signaling and apoptosis of the postnatal nephrons. In this review I discuss the similarities and differences of BMP functions in kidney development, as well as in diseases. PMID- 24217786 TI - HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse. AB - BACKGROUND: Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression free survival (PFS). METHODS: Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher's exact test, Kendall's tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan-Meier method. RESULTS: At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601-0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68 75.25; and p = 0.044, HR 3.33, 95 % CI 1.03-10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22-42.19 and p = 0.036, OR 10.18, 95 % CI 1.16-88.69, respectively). CONCLUSIONS: HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results. PMID- 24217787 TI - Attaining surgical competency and its implications in surgical clinical trial design: a systematic review of the learning curve in laparoscopic and robot assisted laparoscopic colorectal cancer surgery. AB - BACKGROUND: Laparoscopic surgery is increasingly used in the treatment of colorectal cancer and more recently robotic assistance has been advocated. However, the learning curve to achieve surgical proficiency in laparoscopic surgery is ill-defined and subject to many influences. The aim of this review was to comprehensively appraise the literature on the learning curve for laparoscopic and robotic colorectal cancer surgery, and to quantify attainment of surgical proficiency and its implications in surgical clinical trial design. METHODS: A systematic review using a defined search strategy was performed. Included studies had to state an explicit numerical value of the learning curve evaluated by a single parameter or multiple parameters. RESULTS: Thirty-four studies were included, 28 laparoscopic and 6 robot assisted. Of the laparoscopic studies, nine defined the learning curve on the basis of a single parameter. Nine studies used more than one parameter to define learning, and 11 used a cumulative sum (CUSUM) analysis. One study used both a multiparameter and CUSUM analysis. The definition of proficiency was subjective, and the number of operations to achieve it ranged from 5 to 310 cases for laparoscopic and 15-30 cases for robotic surgery. CONCLUSIONS: The learning curve in laparoscopic colorectal surgery is multifaceted and often ill-defined, with poor descriptions of mentorship/supervision. Further, the quantification to attain proficiency is variable. The use of a single parameter to quantify this is simplistic. Multidimensional assessment is recommended; as part of this, the CUSUM model, which assesses trends in multiple surgical outcomes, is useful and appropriate when assessing the learning curve in a clinical setting. PMID- 24217788 TI - Metastatic behavior of upper tract urothelial carcinoma after radical nephroureterectomy: association with primary tumor location. AB - PURPOSE: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter. RESULTS: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131). CONCLUSIONS: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients. PMID- 24217789 TI - Significance of urinary tract involvement in patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). AB - BACKGROUND: Urinary tract involvement in patients with peritoneal surface disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often requires complex urologic resections and reconstruction to achieve optimal cytoreduction. The impact of these combined procedures on surgical outcomes is not well defined. METHODS: A prospective database of CRS/HIPEC procedures was analyzed retrospectively. Type of malignancy, performance status, resection status, hospital and intensive care unit stay, morbidity, mortality, and overall survival were reviewed. RESULTS: A total of 864 patients underwent 933 CRS/HIPEC procedures, while 64 % (550) had preoperative ureteral stent placement. A total of 7.3 % had an additional urologic procedure without an increase in 30-day (p = 0.4) or 90-day (p = 1.0) mortality. Urologic procedures correlated with increased length of operating time (p < 0.001), blood loss (p < 0.001), and length of hospitalization (p = 0.003), yet were not associated with increased overall 30-day major morbidity (grade III/IV, p = 0.14). In multivariate analysis, independent predictors of additional urologic procedures were prior surgical score (p < 0.001), number of resected organs (p = 0.001), and low anterior resection (p = 0.03). Long-term survival was not statistically different between patients with and without urologic resection for low-grade appendiceal primary lesions (p = 0.23), high-grade appendiceal primary lesions (p = 0.40), or colorectal primary lesions (p = 0.14). CONCLUSIONS: Urinary tract involvement in patients with peritoneal surface disease does not increase overall surgical morbidity. Patients with urologic procedures demonstrate survival patterns with meaningful prolongation of life. Urologic involvement should not be considered a contraindication for CRS/HIPEC in patients with resectable peritoneal surface disease. PMID- 24217790 TI - Quilting prevents seroma formation following breast cancer surgery: closing the dead space by quilting prevents seroma following axillary lymph node dissection and mastectomy. AB - BACKGROUND: Seroma is a frequent problem after mastectomy (ME) and axillary lymph node dissection (ALND). Seroma is associated with pain, discomfort, impaired mobilisation and repeated aspirations, often resulting in a surgical site infection (SSI). It has already been demonstrated that minimizing dead space through fixation of the skin flaps to the underlying muscles (quilting) lowers the incidence of seroma. The aim of this study was to evaluate the effect of quilting on the incidence of seroma, and SSI. METHODS: Two consecutive groups with a total of 176 patients following ME and/or ALND were retrospectively compared. Endpoints were the incidence of seroma, and number and volume of aspirations and SSIs. Analysed risk factors were age, ME, lymph node dissection, neoadjuvant therapy, body mass index (BMI) and hypertension. RESULTS: The quilted group (n = 89) scored significantly better on all endpoints compared with the conventional group (n = 87). The incidence of seroma decreased from 80.5 % to 22.5 % (p < 0.01), the mean number of aspirations from 4.86 to 2.40 (p = 0.015), the volume of aspirations from 1660 ml to 611 ml (p = 0.05) and the SSIs from 31.0 % to 11.2 % (p < 0.01). Increasing age and lymph node dissection were found to be risk factors for seroma; quilting was a protective factor. CONCLUSION: Quilting is an effective method for preventing seroma and its complications. PMID- 24217791 TI - Aberrant expression of plastin-3 via copy number gain induces the epithelial mesenchymal transition in circulating colorectal cancer cells. AB - PURPOSE: Plastin-3 (PLS3) is a novel marker for circulating tumor cells (CTCs) in colorectal cancer (CRC). We sought to investigate the mechanisms mediating the aberrant expression of PLS3, the role of PLS3 in the epithelial-mesenchymal transition (EMT), and its association with the acquisition of invasive and metastatic abilities in human CRC. METHODS: The expression levels of PLS3 messenger RNA in the tumor drainage venous blood (TDB) were examined in 177 CRC cases, and the associations between PLS3 expression and Xq23 copy numbers were analyzed in 132 CRC samples. We then established a stable PLS3-expressing CRC cell line and assessed the role of PLS3 in the EMT. RESULTS: In clinical CRC cases, high expression of PLS3 in CTCs of TDB as well as peripheral blood was established as an independent prognostic factor of overall survival (p < 0.001), and the copy number gain of Xq23, which is the locus of the PLS3 gene, was significantly related to PLS3 overexpression. PLS3 induced the EMT via transforming growth factor (TGF)-beta signaling and resulted in the acquisition of invasive ability in CRC cells. CONCLUSIONS: The aberrant expression of PLS3 was associated with copy number gain in CTCs from primary tumors and was involved in the regulation of the EMT, contributing to a poor prognosis in CRC patients. PMID- 24217792 TI - Intraoperative visualization of hepatocellular carcinoma with indocyanine green: revealing the mechanisms behind the glowing tumor. PMID- 24217793 TI - Managing chronic pelvic pain following reconstructive pelvic surgery with transvaginal mesh. AB - In 2001, the US Food and Drug Administration (FDA) approved the first transvaginal mesh kit to treat pelvic organ prolapse (POP). Since the introduction of vaginal mesh kits, some vaginal meshes have been associated with chronic pelvic pain after reconstructive pelvic floor surgery. Pelvic pain results in between 0 % and 30 % of patients following transvaginal mesh placement. Common causes of chronic pelvic pain include pelvic floor muscle spasm, pudendal neuralgia, and infection. Paucity of data exists on the effective management of chronic pelvic pain after pelvic reconstructive surgery with mesh. We outline the management of chronic pelvic pain after transvaginal mesh placement for reconstructive pelvic floor repair based on our clinical experience and adaptation of data used in other aspects of managing chronic pelvic pain conditions. PMID- 24217794 TI - MicroRNA expression aberration in Chinese patients with relapsing remitting multiple sclerosis. AB - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is caused by an abnormal immune system that attacks the central nervous system. MicroRNAs (miRNAs) are known to play essential roles in the immune system. Most of the previous studies about miRNA dysregulation in MS have focused on European populations. In the present study, the miRNA expression profiles associated with Chinese MS patients are investigated. Here, human miRNA expression profiling experiments were performed on the peripheral blood mononuclear leukocytes from ten MS patients and ten healthy controls. Nine overexpressed and six underexpressed miRNAs were found. The 15 miRNAs were validated independently in a second cohort of 40 MS patients and 40 controls by real-time PCR; six miRNAs were significantly abnormally expressed, and principal component analysis of six miRNAs indicated that the MS patients could be clearly differentiated from the healthy controls based on the miRNA expression patterns. This study provided the indications of abnormal miRNA expression patterns in the peripheral blood mononuclear leukocytes of Chinese MS patients. The potential roles of these differentially expressed miRNAs as MS biomarker and in pathogenesis need to be investigated in future studies. PMID- 24217795 TI - Oxidative stress promotes uptake, accumulation, and oligomerization of extracellular alpha-synuclein in oligodendrocytes. AB - The accumulation and aggregation of alpha-synuclein (alpha-Syn) in glial cytoplasmic inclusions originating in oligodendrocytes is a characteristic hallmark of multiple system atrophy, a progressive adult onset neurodegenerative disorder. The origin of alpha-Syn deposition in oligodendrocytes in multiple system atrophy is still unclear, but the uptake of alpha-Syn from the environment after neuronal secretion has been discussed. The present study was undertaken to investigate the consequences of alpha-Syn uptake from the environment in cultured oligodendroglial cells and its localization and potential to form intracellular aggregates in the absence or presence of the microtubule-associated protein tau, which has been demonstrated to act synergistically with alpha-Syn. Primary rat brain oligodendrocytes and clonal oligodendroglial OLN-93 cells were incubated with human recombinant soluble and pre-aggregated alpha-Syn. The data show that oligodendrocytes are capable to take up and internalize soluble and pre aggregated alpha-Syn from their growth medium. In a time-dependent manner, alpha Syn oligomerizes and small intracellular aggregates are formed. These do not exert cytotoxic responses or mitochondrial impairment. Oxidative stress exerted by hydrogen peroxide further promotes alpha-Syn oligomer formation and leads to an enlargement of the aggregates. This process is not affected or modified by the presence of tau in OLN-93 cells. Furthermore, membrane lipid modification by docosahexaenoic acid promotes alpha-Syn uptake and oligomerization, indicating that changing the membrane lipid composition and structure contributes to the protein aggregation process and pathological events. Hence, although alpha-Syn taken up by oligodendrocytes from the environment is not toxic per se, under conditions of oxidative stress, which might occur during chronic disease progression and aging, aggregates are enlarged and eventually may contribute to cytotoxicity and cellular death. PMID- 24217796 TI - Up-regulation of FoxN4 expression in adult spinal cord after injury. AB - FoxN4 (forkhead box N4), which is a transcription factor involved in developing spinal cord and spinal neurogenesis, implied important roles in the central nervous system (CNS). However, its expression and function in the adult CNS lesion are still unclear. In this study, we established a spinal cord injury (SCI) model in adult rats and investigated the expression of FoxN4 in the spinal cord. Western blot analysis revealed that FoxN4 was present in normal spinal cord. It gradually increased, peaked at day 3 after SCI, and then decreased during the following days. Immunohistochemistry further confirmed that FoxN4 was expressed at low levels in gray and white matters in normal condition and increased after SCI. Double immunofluorescence staining showed that FoxN4 is located on neurons and astrocytes, and FoxN4 expression was increased progressively in reactive astrocytes within the vicinity of the lesion, predominately in the white matter. In addition, almost all FoxN4-positive cells also expressed nestin or PCNA. Our data suggested that FoxN4 might play important roles in CNS pathophysiology after SCI. PMID- 24217797 TI - Characterizations of cholinesterases in golden apple snail (Pomacea canaliculata). AB - Cholinesterases (ChEs) have been identified in vertebrates and invertebrates. Inhibition of ChE activity in invertebrates, such as bivalve molluscs, has been used to evaluate the exposure of organophosphates, carbamate pesticides, and heavy metals in the marine system. The golden apple snail (Pomacea canaliculata) is considered as one of the worst invasive alien species harmful to rice and other crops. The ChE(s) in this animal, which has been found recently, but poorly characterized thus far, could serve as biomarker(s) for environmental surveillance as well as a potential target for the pest control. In this study, the tissue distribution, substrate preference, sensitivity to ChE inhibitors, and molecular species of ChEs in P. canaliculata were investigated. It was found that the activities of both AChE and BChE were present in all test tissues. The intestine had the most abundant ChE activities. Both enzymes had fair activities in the head, kidney, and gills. The BChE activity was more sensitive to tetra isopropylpyrophosphoramide (iso-OMPA) than the AChE. Only one BChE molecular species, 5.8S, was found in the intestine and head, whereas two AChE species, 5.8S and 11.6S, were found there. We propose that intestine ChEs of this snail may be potential biomarkers for manipulating pollutions. PMID- 24217798 TI - High current density electrodeposition of silver from silver-containing liquid metal salts with pyridine-N-oxide ligands. AB - New cationic silver-containing ionic liquids were synthesized and used as non aqueous electrolytes for the electrodeposition of silver layers. In the liquid state of these ionic liquids, a silver (i) cation is coordinated by pyridine-N oxide (py-O) ligands in a 1 : 3 metal-to-ligand ratio, although in some cases a different stoichiometry of the silver center crystallized out. As anions, bis(trifluoromethanesulfonyl)imide (Tf2N), trifluoromethanesulfonate (OTf), methanesulfonate (OMs) and nitrate were used, yielding compounds with the formulae [Ag(py-O)3][Tf2N], [Ag(py-O)3][OTf], [Ag(py-O)3][OMs] and [Ag(py O)3][NO3], respectively. The compounds were characterized by CHN analysis, FTIR, NMR, DSC, TGA and the electrodeposition of silver was investigated by cyclic voltammetry, linear potential scans, scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDX). With the exception of [Ag(py O)3][Tf2N], which melts at 108 degrees C, all the silver(i) compounds have a melting point below 80 degrees C and were tested as electrolytes for silver electrodeposition. Interestingly, very high current densities were observed at a potential of -0.5 V vs. Ag/Ag(+) for the compounds with fluorine-free anions, i.e. [Ag(py-O)3][NO3] (current density of -10 A dm(-2)) and [Ag(py-O)3][OMs] ( 6.5 A dm(-2)). The maximum current density of the compound with the fluorinated anion trifluoromethanesulfonate, [Ag(py-O)3][OTf], was much lower: -2.5 A dm(-2) at -0.5 V vs. Ag/Ag(+). Addition of an excess of ligand to [Ag(py-O)3][OTf] resulted in the formation of the room-temperature ionic liquid [Ag(py-O)6][OTf]. A current density of -5 A dm(-2) was observed at -0.5 V vs. Ag/Ag(+) for this low viscous silver salt. The crystal structures of several silver complexes could be determined by X-ray diffraction, and it was found that several of them had a stoichiometry different from the 1 : 3 metal-to-ligand ratio used in their synthesis. This indicates that the compounds form crystals with a composition different from that of the molten state. The electrochemical properties were measured in the liquid state, where the metal-to-ligand ratio was 1 : 3. Single crystal X-ray diffraction measurements showed that silver(i) is six coordinate in [Ag(py-O)3][Tf2N] and [Ag(py-O)3][OTf], while it is five coordinate in the other complexes. In [Ag3(py-O)8][OTf]3, there are two different coordination environments for silver ions: six coordinate central silver ions and five coordinate for the outer silver ions. In some of the silver(i) complexes, silver silver interactions were observed in the solid state. PMID- 24217801 TI - Laparoscopic ureterocalicostomy for complicated upper urinary tract obstruction: mid-term follow-up. AB - PURPOSE: To report on the largest series of laparoscopic ureterocalicostomies done for complicated upper urinary obstruction. METHODS: We retrospectively reviewed the data from 6 transperitoneal laparoscopic ureterocalicostomies performed in our institution from January 2008 to January 2012. Symptomatic complicated upper urinary obstruction was the main reason for all the procedures. The recorded data included age, gender, clinical presentation, duration of symptoms, laterality, mean operative time, hospital stay, complications and clinical and functional outcomes. RESULTS: The median patient age was 20.1 (2-44) years, and all patients were females. Patients underwent laparoscopic ureterocalicostomy due to previous failed procedures (3 patients), anatomic abnormalities (2 patients) and a severe upper ureteral stenosis (1 patient). The median operative time was 215 (180-270) min. There were no major complications. There were no conversions to open surgery. In a median follow-up of 30 (8-56) months, all patients presented with clinical and radiological improvement with no signs of obstruction. In all cases, the postoperative renal scintigraphy revealed a T1/2 lower than 10 min. CONCLUSION: Laparoscopic ureterocalicostomy is feasible and associated with high success rate in well-selected cases with complicated upper urinary obstructions. PMID- 24217802 TI - Membranous glomerulonephritis with crescents. AB - PURPOSE: The coexistence of membranous glomerulonephritis (MGN) and necrotizing and crescentic glomerulonephritis (NCGN) is an unusual finding in a renal biopsy except in lupus nephritis. Little is known about whether these lesions are causally related in any clinical setting. METHODS: We reviewed the pathology, presentation, and clinical course of 13 non-lupus patients with combined MGN and NCGN in native kidney biopsies (nine females, four males; median age 69 years), with particular attention to evidence of secondary MGN. Additional IgG subclass and phospholipase A2 receptor (PLA2R) immunofluorescence studies were conducted in seven cases. RESULTS: Eight biopsies were pauci-immune other than the capillary wall deposits of MGN; one patient had a non-lupus immune complex disease, and four had mesangial deposits, including one with rare subendothelial deposits. None had anti-glomerular basement membrane disease. IgG4 was dominant or codominant in the capillary wall deposits in three cases and virtually absent in four; PLA2R was positive in two cases, and negative in five. Seven patients were judged to have secondary MGN, including five of eight ANCA+ patients. Twelve patients were treated with combinations of steroids, cyclophosphamide, rituximab, followed by durable response in seven and relentless progression to end stage renal disease in four. CONCLUSIONS: Secondary MGN occurs with higher frequency in ANCA-positive NCGN than in the general MGN population. A causal relationship between MGN and NCGN was not established in any patient, but circumstances suggest a common cause in several, including immune complex disease, drug reaction and paraneoplastic syndrome. PMID- 24217803 TI - What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy? AB - Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal transplant recipients or comparing sirolimus versus everolimus impact on bone, so only general conclusions could be drawn. Hence, the use of mTORi might be useful in patients with PRO due to their possible potential to inhibit osteoclast activity which might lead to a decreased rate of bone resorption. In addition, it should be also emphasized that they might inhibit osteoblast activity which may lead to a decreased bone formation and adynamic bone disease. Further studies are urgently needed to solve these important clinical dilemmas. PMID- 24217804 TI - Metabolomics insights into pathophysiological mechanisms of nephrology. AB - Kidney diseases (KD), a major public health problem that affects about 10 % of the general population, manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. However, current approaches based on renal histopathological results and clinical parameters lack sensitivity and are not sufficient to characterize the category and progression of nephrology or to predict nephrology progression risk reliably or to guide preventive interventions. The high incidence and financial burden of KD make it imperative to diagnose KD at early stages when therapeutic interventions are far more effective. Nowadays, the appearance of metabolomics (the high-throughput measurement and analysis of metabolites) has provided the framework for a comprehensive analysis of KD and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology. Changes in the concentration profiles of a number of small-molecule metabolites found in either blood or urine can be used to localize kidney damage or assess kidneys suffering from injury. The power of metabolomics allows unparalleled opportunity to query the molecular mechanisms of KD. Novel metabolomics technologies have the ability to provide a deeper understanding of the disease beyond classical histopathology, redefine the characteristics of the disease state, and identify novel approaches to reduce renal failure. This review gives an overview of its application to important areas in clinical nephrology, with a particular focus on biomarker discovery. Great strides forward are being made in breaking down important barriers to the successful prevention and treatment of this devastating disorder. PMID- 24217807 TI - Germinal center-independent, IgM-mediated autoimmunity in sanroque mice lacking Obf1. AB - Mice homozygous for a point mutation in the Rc3h1 gene encoding Roquin1, designated sanroque mice, develop a severe antibody-mediated autoimmune condition. The disease is T-cell intrinsic, exacerbated by macrophage-intrinsic defects and driven by excessive T follicular helper cell generation and spontaneous germinal centre (GC) formation. This culminates in abnormally high numbers of plasma cells secreting high-affinity autoreactive immunoglobulin G (IgG). Obf1 is a transcriptional co-activator required for normal T-cell dependent antibody responses, and it is essential for GC formation under all circumstances so far tested. We crossed sanroque mice with Obf1-null mice to determine whether the hyperactivity of sanroque T cells could drive Obf1(-/-) B cells to differentiate to GC B cells, or conversely, if Obf1 loss would prevent sanroque-mediated autoimmune disease. Surprisingly, while sanroque/Obf1(-/-) mice did not form GC, they still developed autoimmune disease and succumbed even more rapidly than did sanroque mice. The disease was mediated by autoreactive IgM, which may have been derived from a pre-existing population of autoreactive B cells in the Obf1(-/-) mice responding to the over-exuberant activity of sanroque CD4 cells. PMID- 24217806 TI - Obesity and late-age survival without major disease or disability in older women. AB - IMPORTANCE: The effect of obesity on late-age survival in women without disease or disability is unknown. OBJECTIVE: To investigate whether higher baseline body mass index and waist circumference affect women's survival to 85 years of age without major chronic disease (coronary disease, stroke, cancer, diabetes mellitus, or hip fracture) and mobility disability. DESIGN, SETTING, AND PARTICIPANTS: Examination of 36,611 women from the Women's Health Initiative observational study and clinical trial programs who could have reached 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US clinical centers from October 1993 through December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% CIs for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics. MAIN OUTCOMES AND MEASURES: Mutually exclusive classifications: (1) survived without major chronic disease and without mobility disability (healthy); (2) survived with 1 or more major chronic disease at baseline but without new disease or disability (prevalent diseased); (3) survived and developed 1 or more major chronic disease but not disability during study follow-up (incident diseased); (4) survived and developed mobility disability with or without disease (disabled); and (5) did not survive (died). RESULTS: Mean (SD) baseline age was 72.4 (3.0) years (range, 66-81 years). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19.0%, 14.7%, 23.2%, 18.3%, and 24.8%, respectively. Compared with healthy-weight women, underweight and obese women were more likely to die before 85 years of age. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to healthy weight women, adjusted odds ratios (95% CIs) of mobility disability were 1.6 (1.5 1.8) for overweight women and 3.2 (2.9-3.6), 6.6 (5.4-8.1), and 6.7 (4.8-9.2) for class I, II, and III obesity, respectively. Waist circumference greater than 88 cm was also associated with higher risk of earlier death, incident disease, and mobility disability. CONCLUSIONS AND RELEVANCE: Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before 85 years of age in older women. PMID- 24217808 TI - In vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumours. AB - Small interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-alpha (IFNalpha) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNalpha were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies. PMID- 24217809 TI - Glucocorticoid-mediated repression of T-cell receptor signalling is impaired in glucocorticoid receptor exon 2-disrupted mice. AB - Studies using glucocorticoid receptor exon 2-disrupted knockout (GR2KO) mice provided strong evidence against an obligatory role for glucocorticoid receptor (GR) signalling in T-cell selection. These mice express a truncated form of the GR that is incapable of transmitting a range of glucocorticoid (GC)-induced signals, including GC-induced thymocyte death. However, one study that suggested that truncated GR function is preserved in the context of GR-mediated repression of T-cell activation-induced genes, challenged earlier conclusions derived from the use of these mice. Because GR versus T-cell receptor (TCR) signalling cross talk is the means by which GCs are hypothesized to have a role in T-cell selection, we reassessed the utility of GR2KO mice to study the role of the GR in this process. Here, we show that GR-mediated repression of TCR signalling is impaired in GR2KO T cells in terms of TCR-induced activation, proliferation and cytokine production. GC-induced apoptosis was largely abolished in peripheral T cells, and induction of the GC-responsive molecule, interleukin-7 receptor, was also severely reduced in GR2KO thymocytes. Together, these data strongly re affirm conclusions derived from earlier studies of these mice that the GR is not obligatory for normal T-cell selection. PMID- 24217810 TI - Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell-based cancer immunotherapy. AB - Dendritic cell (DC)-based immunotherapy has recently demonstrated a great potential for clinical applications; however, additional progress in the methods of tumor-specific antigen delivery to DCs is necessary for the further development of anti-tumor vaccines. To this end, a capsid-optimized adeno associated virus serotype 6 (AAV6-T492V+S663V) vector was developed by site directed mutagenesis of surface-exposed serine (S) and threonine (T) residues, which have a critical role in intracellular trafficking of AAV vectors. This double-mutant AAV6 vector had ~ 5-fold greater transduction efficiency in monocyte-derived DCs (moDCs) compared with wild-type (WT)-AAV6 vectors. The increase in the transduction efficiency correlated with the improved nuclear translocation of AAV6-T492V+S663V over that of the WT-AAV6 vector. Additional studies of the CD11c promoter identified critical regulatory elements that fit into the AAV expression cassette and drive EGFP expression in moDCs. Development of a chimeric promoter (chmCD11c) that contains functional modules of CD11c and a Simian virus (SV40) enhancer element dramatically increased the EGFP expression in moDCs. MoDCs transduced by the capsid-optimized AAV6 vector carrying human prostate-specific antigen (hPSA) driven by CBA (AAV6-T492V+S663V-CBA-hPSA) or chmCd11c (AAV6-T492V+S663V-chmCD11c-hPSA) generated specific T-cell clone proliferation and superior cytotoxic T lymphocytes (CTLs) with higher killing capability against human prostate adenocarcinoma cells, LNCaP, compared with WT AAV6 induced CTLs. Taken together, these studies suggest that optimization of capsid and promoter components of AAV vectors can be a useful approach for efficient targeting of moDCs and may prove to be a promising tool for cancer immunotherapy. PMID- 24217811 TI - Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis. AB - Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity. PMID- 24217812 TI - How T follicular helper cells and the germinal centre response change with age. AB - Normal ageing is accompanied by a decline in the function of the immune system that causes an increased susceptibility to infections and an impaired response to vaccination in older individuals. This results in an increased disease burden in the aged population, even with good immunisation programmes in place. The decreased response to vaccination is partly due to the diminution of the germinal centre response with age, caused by impaired T-cell help to B cells. Within the germinal centre, T-cell help is provided by a specialised subset of CD4(+) T cells; T follicular helper (Tfh) cells. Tfh cells provide survival and selection signals to germinal centre B cells, allowing them to egress from the germinal centre and become long-live plasma cells or memory B cells, and provide life-long protection against subsequent infection. This review will discuss the cellular and molecular changes in both Tfh cells and germinal centre B cells that occur with advancing age, which result in a smaller germinal centre response and a less effective response to immunisation. PMID- 24217813 TI - IgM autoantibodies: Roquin and Bob1ng to a different tune. PMID- 24217814 TI - Psychrobacter immobilis septicemia in a boy with X-linked chronic granulomatous disease and fulminant hepatic failure. AB - A 16-year old boy with chronic granulomatous disease (CGD) developed Psychrobacter immobilis septicemia during a course of fulminant hepatic failure. The patient died despite aggressive management with antimicrobials and corticosteroids. While Psychrobacter immobilis rarely affects humans, it should be considered an organism that can cause sepsis in patients with CGD. PMID- 24217815 TI - Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature. AB - We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features. PMID- 24217816 TI - Allogeneic bone marrow transplantation appears to ameliorate IgA nephropathy in a patient with X-linked thrombocytopenia. AB - Wiskott-Aldrich syndrome (WAS) is caused by a mutation in the WAS gene, and it is clinically characterized by the triad of thrombocytopenia, eczema and immunodeficiency. X-linked thrombocytopenia (XLT), which is a clinically mild form of WAS, is also caused by a WAS gene mutation. Patients with WAS/XLT sometimes also have autoimmune diseases such as IgA nephropathy. Progression of IgA nephropathy may lead to chronic renal failure with a poor prognosis. Here, we describe an XLT patient who also had IgA nephropathy. The patient underwent bone marrow transplantation (BMT) because of an associated-lymphoproliferative disorder, and clinical and histological improvement in his IgA nephropathy was observed after BMT. The amount of galactose-deficient IgA in the patient's serum markedly decreased after BMT. Therefore, immunological reconstitution might improve autoimmune diseases in patients with WAS/XLT. PMID- 24217817 TI - Increased circulating Th17 cell populations and elevated CSF osteopontin and IL 17 concentrations in patients with Guillain-Barre syndrome. AB - PURPOSE: Guillain-Barre syndrome (GBS) is an acute post-infectious immune mediated demyelinating disease of the peripheral nervous system. Th17 cells and osteopontin (OPN) have been implicated in the development of autoimmune diseases, but little is known about their relationship and roles in the pathogenesis of GBS. METHODS: In this study, we used flow cytometry to evaluate peripheral numbers of Th17, real-time polymerase chain reaction to assay mRNA expression of RORgammat, and enzyme-linked immunosorbent assay to determined OPN and IL-17 concentrations. RESULTS: The frequency of Th17 cells was significantly higher in the peripheral blood of acute-stage GBS patients comparison with other non inflammatory neurological diseases (OND). In line with these observations, the levels of mRNA expression of RORgammat in peripheral blood mononuclear cells and the concentrations IL-17 in both plasma and cerebrospinal fluid (CSF) were significantly higher in the acute-stage GBS than stable-stage GBS. OPN concentrations were significantly increased in the CSF of acute-stage GBS patients compared to OND. Circulating Th17 cell populations and CSF OPN levels, respectively, are correlated with GBS disability scale scores (GDSs), and there was a positive correlation between them. CONCLUSION: In summary, our preliminary findings suggest that both Th17 and OPN may be associated with the pathogenesis of GBS. PMID- 24217818 TI - [PPMP as a forum for female academics]. PMID- 24217819 TI - [Are urban dwellers more depressed and anxious than the rural population? Results of a representative survey]. PMID- 24217820 TI - [Position statement: Are urban dwellers more depressed and anxious than the rural population? Results of a representative survey]. PMID- 24217821 TI - First-line combination therapy with rituximab and corticosteroids is effective and safe for pemphigus. PMID- 24217822 TI - The evaluation of patients with burns during fifteen years period. AB - AIMS: Burn is a major health problem that cause of mortality, morbidity and psychological problems in children and adults throughout the world. The aim of this study was to evaluate the epidemiological, etiological features and outcomes of burns in the southeast region of Turkey. PATIENTS AND METHODS: A total of 3010 burn patients (age vary between 2 month to 95 years old) that admitted to the Dicle University burn center during the 15 years period (1994-2008) were reviewed. Age, gender, demographic characteristics, length of hospital stay of patients, etiology and degree of burns, cause of nosocomial infections, the total body surface area (TBSA) percentage and outcomes were analyzed. RESULTS: Of 3010 patients, 1602 (53.2%) cases were female and 1408 (46.8%) were male. The mean age was 10.51+/-13.45. The most of patients (58.1%, 1748 patients) were <= 5 years old, 19.9% (598) were 6-15, 20.1% (606) were 16-50 and 1.9% (58) were >=51 years old. Burn type of cases were including: 1956 (65%) scalding burns, 624 (20.7%) flame burns and 430 (14.3%) electrical burns. Degree of burns were including: 22 (0.7%) first-degree, 2706 (89.9%) second-degree and 282 (9.4%) third-degree burns. The mean of length of hospitalization was 13.25 +/-10.77 days. The most frequent isolated microorganisms were Pseudomonas aeruginosa (55%, 553), Acinetobacter spp. (13%, 128), and Escherichia coli (8%, 78). Mortality rate was 4.6%. CONCLUSIONS: The epidemiology of burns may vary according to lifestyles, age, living conditions and socio-economic status among different regions and hospitals. Improvement of life conditions and socio-economic status, trainings, periodic studies of nosocomial infections and increasing the number of burn centers, would contribute to reduction of deaths due to burns. PMID- 24217823 TI - Calcium score of coronary artery stratifies the risk of obstructive coronary artery diseases. AB - BACKGROUND AND AIMS: Coronary heart disease is a major health problem in Malaysia with high morbidity and mortality. Common primary screening tool of cardiovascular risk stratification is exercise treadmill test (ETT). This communication is to determine the performance of coronary artery calcium score a new method to stratify the presence of obstructive coronary artery disease (CAD) in comparison to traditional ETT in patients having coronary artery diseases. MATERIALS AND METHODS: Patients between 30 to 60 years old attended the ETT to screen for ischemic heart disease were recruited for Agatston coronary artery calcium score (CACS) of multi-sliced computed tomography (MSCT). Subsequently all patients underwent a full MSCT coronary angiography. The major determinant was the state of CAD whether obstructive (50% stenosis or more) or non-obstructive (less than 50% stenosis). All patients diagnosed with obstructive CAD on MSCT coronary angiogram were subjected to invasive coronary angiogram (ICA) to confirm the findings and planned the need for revascularization. RESULTS: The CACS was 100% sensitivity and 97.5% specificity in detecting obstructive CAD at the optimal cut-off value of 106.5 and above. The positive predictive value (PPV) at CACS >= 106 was 71.4% and the negative predictive value (NPV) was consistent at 100%. Compare to ETT, the CACS discriminative value and diagnostic performance was much better (PPV 71.4% vs. 45.5%), respectively. CONCLUSION: CACS can be a good diagnostic screening tool in patients suspected of CAD, and particularly within the non-diagnostic ETT subgroup with low to moderate cardiovascular risks. PMID- 24217824 TI - Classification and comparative study of vitiligo in Southeast of Turkey with biochemical and immunological parameters. AB - OBJECTIVE: To investigate classification and comparative with biochemical and immunological parameters of vitiligo disease in Southeast of Turkey. PATIENTS AND METHODS: 148 patients who referred to the Department & Dermatology and Venereology with the complaint of vitiligo were selected. All patients gave informed consent for participation in the study. The patients were classified according to types of the skin. The complete blood cell and biochemical laboratory tests, ASO, CRP, RF, ANA, thyroid hormone levels were examined. RESULTS: In the evaluation of 148 vitiligo patients; we didn't observe any significant difference between age and sex groups. We observed the maximum number of patients in the ages of 20-29 years and the most common types of clinical and focal types. We compared the childeren and adult patients according to their skin types, the difference was significant. We viewed that the onset of the disease commonly first in the face area. Koebner phenomenon 17 (11.48%), halo nevus 5 (3.38%) and leucotrichia 5 (3.38%) of patients were positive. CONCLUSION: Vitiligo is associated with loss of color by the destruction of melanocytes. The incidence of vitiligo is 1-2% and is found in every race. This study is important for the reason of the first research which evaluates vitiligo patients in southeast of Turkey. PMID- 24217825 TI - Risk of mental health disorders among farmers involved in palm plantation occupation. AB - OBJECTIVE: The aim of this study was to define mental health status of palm plantation farmers in Muar, Johor, Malaysia. MATERIALS AND METHODS: 47 male farmers volunteered to join this study from three rural districts in southern Malaysia. Anthropometric measurements, demographic data including smoking habits and the short form of the Depression-Anxiety-Stress Scales (DASS-21) to assess mental health status were obtained in an interview. RESULTS: Mean and SD age of participants was 30.17 +/- 4.86 years. Mean BMI of subjects was 22.86 +/- 3.88 kg/m2. Most subjects (76.6%) were smokers. The prevalence of mild to moderate anxiety was 27.7% and Mild to moderate depression was 8.5%. CONCLUSIONS: This study revealed high prevalence of anxiety and smoking in palm plantation workers and that smoking habits can be related to their higher anxiety level. PMID- 24217826 TI - Nurses compliance to hand hygiene practice and knowledge at Klang Valley hospital. AB - BACKGROUND AND AIMS: Hand hygiene is the most important measure in the prevention of healthcare-associated infections (HCAI). Adherence to hand hygiene protocols in hospital by nurses enables in prevention and control the HCAI. The main aim of the present study was to assess nurses' compliance to hand hygiene practice and knowledge in a hospital. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted in the intensive care units of a hospital in Kuala Lumpur. A total of 84 registered nurses from the intensive care were recruited for this study. A self-administered questionnaire was deployed to measure knowledge and compliance about hand hygiene. RESULTS: The findings showed the total mean and standard deviation of knowledge (60.65+/-4.213) and compliance (84.65+/-7.024) to be high among the respondents. There were no significant differences with the knowledge and compliance to hand hygiene with respondents' age groups with a p value >0.05. However, there were significant differences between respondents' years of service with the knowledge and compliance with p values <0.05. The results showed significant differences between respondents' with post basic course with compliance to hand hygiene with a p value <0.05 actual p value added (p = 0.001). There were no significant differences between the respondents' post basic course with knowledge to hand hygiene with p values >0.05 actual p value added (p=0.072). CONCLUSION: Nurses compliance to hand hygiene practice and knowledge was good. Nurses' years of service have great implications on compliance to hand hygiene practice. The study opines that constant reinforcement and motivation are required by the hospital infection control team to impart hand hygiene practice. PMID- 24217827 TI - Abdominal wall reconstruction after resection of an enterocutaneous fistula with an island pedicled anterolateral thigh perforator flap. Case report. AB - Entero-cutaneous fistula resulting from a locally invasive large bowel carcinoma is a difficult surgical challenge. En-bloc resection of the involved organs and the entero-cutaneous fistula tract with a healthy tissue margin will result in a composite abdominal wall defect that requires closure. Reconstructive surgical options include primary closure, components separation and the use of local, regional or free flaps with or without prosthetic mesh. We report a case of an abdominal enterocutaneous fistula secondary to a locally invasive sigmoid carcinoma, which was reconstructed with a pedicled antero-lateral thigh perforator (ALT) flap. To our knowledge, this is the first case of a malignant entero-cutaneous fistula, which was reconstructed with an ALT flap. PMID- 24217828 TI - Low back pain radiating to the leg: an atypical cause. AB - This study reports the case of a 47-year old female with low back pain radiating to groin and anterior regions of the left thigh and leg. At symptoms onset, electromyography showed left L3-L4 radiculopathy, and nuclear magnetic resonance revealed disc protrusion at the same level with impingement of the spinal nerve root. The clinical symptoms were ascribed to lumbar disco-radicular conflict. The patient underwent steroidal anti-inflammatory treatment with epidural steroid injections, chiropractic spinal manipulations and rehabilitation program, with no relief. Thirteen months after the onset of pain, a computed tomography of sacroiliac joints showed osteolytic lesion in the iliac bone of left joint, and a bone scintigraphy highlighted foci of intense uptake at left iliac bone and left proximal extremity of the femur. The bone biopsy and pathological examinations showed findings consistent with large B-cell non-Hodgkin lymphoma. This case report highlights the fact that in making differential diagnosis of low back pain radiating to the leg we have to consider the rare possibility that pain can be due to non-Hodgkin lymphoma that involves simultaneously the iliac bone and proximal extremity of the femur. PMID- 24217829 TI - A less aggressive therapeutic option for electrical storm. AB - Electrical storm (ES) describes the rapidly clustering ventricular fibrillation (VF) that requires multiple cardioversions. Emerging evidence suggests that Purkinje arborization and sympathetic nerve regeneration play a major role in initiating malignant arrhythmias. We report the case of two patients who, after having survived an acute myocardial infarction (MI), developed repetitive episodes of polymorphic ventricular tachycardia and VF one week after percutaneous revascularization, triggered by monomorphic premature ventricular contractions (PVCs). Owing to repetitive and drug-refractory VF episodes, temporary atrial overdrive pacing was attempted with complete suppression of VF. In the following month, recurrence of ventricular arrhythmia was inversely related to the atrial pacing rate. Although antiarrhythmic drugs other than beta blockers had been discontinued, neither PVCs nor ventricular arrhythmias recurred at one-month follow-up when the lower pacing rate was set at 60 bpm. In conclusion in these patients, ES was likely related to nerve sprouting after ischemic injury. This chaotic phenomenon occurs early after tissue damage and shows a peak seven days after acute MI with degeneration of superfluous axon branches. High pacing rates can reduce early after depolarizations and suppress PVCs, thus preventing ES. On these grounds, ES patients may be treated with temporary overdrive pacing rather than early radiofrequency ablation. PMID- 24217830 TI - Single incision laparoscopic surgery (SILS) inguinal hernia repair - recent clinical experiences of this novel technique. AB - Inguinal hernia remains the most commonly encountered surgical problem. Various methods of repair have been described, and the most suitable one debated. Single port access (SPA) surgery is a rapidly evolving field, and has the advantage of affording 'scarless' surgery. Single incision laparoscopic surgery (SILS) for inguinal hernia repair is seen to be feasible in both total extraperitoneal (TEP) and transabdominal pre-peritoneal (TAPP) approaches. Data and peri-operative information on both of these however are limited. We aimed to review the clinical experience, feasibility and short term complications related to laparoscopic inguinal hernia repair via single port access. A literature search was performed using Google Scholar, Springerlink Library, Highwire Press, Surgical Endoscopy Journal, World Journal of Surgery and Medscape. The following search terms were used: laparoscopic hernia repair, TAPP, TEP, single incision laparoscopic surgery (SILS). Fourteen articles in English language related to SILS inguinal hernia repair were identified. Nine articles were related to TEP repair and the remaining 5 to TAPP. A total of 340 patients were reported within these studies: 294 patients having a TEP repair and 46 a TAPP. Only two cases of recurrence were reported. Various ports have been utilized, including the SILS port, Tri-Port and a custom- made port using conventional laparoscopic instruments. The duration of surgery was 40-100 minutes and the average length of hospital stay was one day. Early outcomes of this novel technique show it to be feasible, safe and with potentially better cosmetic outcome. PMID- 24217831 TI - Treatment of resistant insomnia and major depression. AB - Daily rhythms regulate everiday life and sleep/wake alternation is the best expression of this. Disruptions in biological rhythms is strongly associated with mood disorders, often being the major feature of this, major depressive disorder first of all. Although stabilization of rhythms produced by treatments have important outcome on therapeutic efficacy, insomnia often remains an unresolved symptom when major depression has otherwise been successfully treated with antidepressant. We review scientific literature in order to better clarify how to better approach insomnia as a clinical aspect to investigate and to early treat while treating other psychiatric conditions, major depression in particular. Insomnia is associated with impaired quality of life. It can be resolved with adequate diagnosis and treatment: it should be considered a comorbid condition and should be early identificated and treated in a multidisciplinary way, so that the ideal of treatment for patients with treatment resistant insomnia in major depression is an integration of non-pharmacologic measures, along with judicious use of medication, often used as an adjunctive therapy. PMID- 24217832 TI - [Internal medicine and cardiovascular evaluation of preoperative and perioperative patients undergoing ophthalmic surgery]. AB - Ophthalmic surgery would a surgical practice with fewer complications compared to other types of surgery. This is only true in part, because of the elderly population of reference. So, in cataract surgery we are faced with a patient with heart disease which carries the signs of aging and degenerative consequences linked to it. The interventions performed in patients with heart disease are still potentially have a greater risk, although site preparation and monitoring during and after surgery in recent years have allowed greater safety for patients and an overall reduction in morbidity and mortality. It is stressed so the importance of a correct clinical diagnosis of the general patient for a better stratification of cardiovascular risk for ophthalmic surgery. It must therefore avoid the most frequent sequelae, such as the ICC, arrhythmias and hypertensive crises. One purpose of a Service of Internal Medicine, like ours, totally dedicated to the functional requirements of the assistance of ophthalmologic patients, both during hospitalization, and in prehospitalization, and especially in Day Hospital and in Day Service, for the cardiac risk stratification in ophthalmic surgery, is to ensure firstly to the patient and then to colleagues ophthalmologist and surgeons and anesthetists the greater security on the plane predictive for reducing perioperative and postoperative morbidity and mortality. PMID- 24217833 TI - [Stabilometric analysis in patients affected by maculopathy]. AB - OBJECTIVES: The walk is strictly influenced by vision, that's essential for the position of the body in the space during the walk cycle and the postural control. The quality of life related to the vision is widely highlighted in literature: for example Brown et al. in 2005 underlined the comparison from DMLE and chronic ills, like HIV, angina, dialysis, advanced prostate tumor, stroke, and heart attack. Peripheral low vision appeared the most crippling aspect to the walk, but in recent years a lot of studies stressed the walk difficulty in patients with central low vision. MATERIALS AND METHODS: Our study has been carried out in partnership between Ophtalmic Department and Physiatrist Department. Its aim was to evaluate static posture in patients affected by maculopathy. We picked out subjects affected by maculopathy with central low vision due to a variety of causes but with preserved peripheral vision. RESULTS: Test trials had the purpose to investigate different aspects of static posture, in subjects affected by central low vision. It was related to risk of falling and faulty postures, that are pathologically in a long term. CONCLUSIONS: Our study claimed that in stabilometric analysis the differences between patients affected by maculopathy and control group aren't statistically significant. PMID- 24217834 TI - Comparison of endoscopic retrograde cholangiopancreatography between elderly and younger patients for common bile duct stones. AB - BACKGROUND: Choledocholithiasis is increasing in elderly subjects. The introduction of endoscopic retrograde cholangiopancreatography with biliary sphincterotomy has almost replaced surgery in the treatment of this condition. The aim of the present study was to evaluate the rates of successful clearance of common bile duct stones and the endoscopic techniques used in a population aged 75 years or older compared with those in a younger age group. MATERIALS AND METHODS: A retrospective analysis was made of data related patients who underwent endoscopic retrograde cholangiopancreatography for choledocolithiasis in the period 2010-2011. For all patients, factors such as sex, age at diagnosis, endoscopic treatment (stone extraction using baskets and balloon, mechanical lithotripsy and balloon dilatation of the ampulla, placement of a stent or a naso biliary tube) and need of surgery were analysed. Two groups of patients were identified: patients aged <75 years (Group A) and patients aged >=75 years (Group B). For the statistical analysis Mann-Whitney test and Fischer's Exact test were used. RESULTS: A total of 234 patients were enrolled in the study (94 in Group A, 140 in Group B). No statistically significant differences were observed as far concerns sex, previous cholecystectomy, gallbladder stones and periampullary diverticula, but only for common bile duct dilatation. Complete clearance of common bile duct stones was achieved in 230 patients (97.5%). CONCLUSIONS: The present data are in keeping with those presented in the literature, which confirm that endoscopic retrograde cholangiopancreatography is a safe and effective procedure also in older patients. PMID- 24217835 TI - Can early diagnosis and partial meniscectomy improve quality of life in patients with lateral discoid meniscus? AB - OBJECTIVES: To evaluate clinical and radiographic mid-term outcomes and improvement in quality of life in pediatric patients affected by LDM and who underwent partial or total/subtotal meniscectomy. MATERIALS AND METHODS: 28 patients (12 M, 16 F), mean age 8.3 years old (range: 6-13) affected by LDM with symptoms and/or meniscal tears, mean follow up: 2 years and 4 months (range: 24 52 months). Symptoms included: pain, swelling, articular block, limitation to knee extention, meniscal instability and formation of meniscal cysts. 23 patients treated with partial meniscectomy, 5 by total/subtotal meniscectomy. All of them have been clinically evaluated using the Ikeuchi scale and the POSNA questionnaire; for radiological evaluation we used the Tapper-Hoover grading scale. RESULTS: Ikeuchi: In 23 patients underwent partial meniscectomy: 21 excellent and 2 good; in 5 patients underwent total/subtotal meniscectomy: 1 excellent, 2 good and 2 average. POSNA presurgical mean score: partial meniscectomy: 70 (range 66.8-73.6), total/subtotal meniscectomy: 58.7 (56.9 62.2). POSNA presurgical mean score: partial meniscectomy: 92.4 (range 88.7-98), total/subtotal meniscectomy: 81.2 (range 78.3-85.6). Tapper-Hoover: in 23 patients underwent partial meniscectomy: 17 were classified grade I, 5 grade II, 1 grade III; in 5 patients underwent total/subtotal meniscectomy: 2 were classified grade II and 3 grade III. These ones evidenced further signs of chondromalacia on articular surfaces, in the lateral area of knee joint. DISCUSSION: Significant improvement in quality of life, evidenced in all patients (p = 0.048 in those underwent total/subtotal meniscectomy, p = 0.011 in those underwent partial meniscectomy), but especially in patients who underwent partial meniscectomy with absence of meniscal tears (p = 0.033), supports how important can be early diagnosis of LDM in childhood. We assert that early diagnosis and conservative treatment (partial meniscectomy) could reduce risks in development of chondromalacia, in those patients affected by LDM, because of its association with better clinical, radiographic and in quality of life mid-term results. PMID- 24217836 TI - Early childhood caries (ECC) and neglect in child care: analysis of an Italian sample. AB - AIM: Dental caries was identified as the single most common chronic childhood disease; its prevention should be a priority for dentists. With the aim of describing the correlation between early childhood caries (ECC) and the phenomenon of child neglect, a questionnaire which recorded socio-economic and dental service use data was provided to a randomly chosen sample of parents at three pediatric health service centers in Bari (Italy). MATERIALS AND METHODS: In order to evaluate the association among risk factors and ECC, contingency tables were created and the value of the Odds Ratio (OR) was calculated, indicating the confidence intervals and chi square values. A student's t-test for independent samples was performed to evaluate the differences between the averages. A value of p<=0.5 was considered to be significant for all tests used. RESULTS: Of the 63 children examined, 61.9% (n=39; 95%CL=49.9- 73.9) presented with ECC, of which 47.6% (n=30; 95%CL=34.9-60.6) were classified as Wyne's Type I; 12.7% (n=8; 95%CL=5.6-23.5) were classified as Type II; and 1.6% (n=1; 95%CL=0-8.5) as Type III. Interestingly, the frequency of Types II and III were shown to be higher in low-income families (chi-square=8.50; p=0.03). CONCLUSION: Dentists should recognize children's susceptibility to ECC and their exposure to risk factors for neglect, thus facilitating a primary prevention visit. PMID- 24217837 TI - Extraskeletal Ewing's Sarcoma: insight into a ten years follow-up. AB - Extraskeletal Ewing's sarcoma is a rare malignant soft tissue tumor, classified within the Ewing's Sarcoma Family Tumors. While the classical Ewing's Sarcoma affects mainly the bone during youth, the Extraskeletal histotype differs for age incidence, primary location and prognosis. Peak incidence and typical location are during adolescence and in the extremities respectively. We report a 30 year old woman case with a positive outcome after ten years from first diagnosis of Extraskeletal Ewing's sarcoma. Treatment was achieved through surgical resection plus adjuvant chemoradiotherapy derived from EW93 and IRS III trials. Conclusion. Our report represents an unusual case due to age of presentation, neoplasm location and long survival reached. In last decades several trials results demonstrated that long survival could be achieved by combined surgery and adjuvant multi-drug treatment. PMID- 24217838 TI - [A serious complication due to liquid silicone injection in the legs for cosmetic purpose]. AB - Liquid injectable silicone has been used to increase volume in determined cutaneous districts, particularly in aesthetical reconstructive surgery. Although considered biologically inert for a long time this substance produced various complications as granulomatous foreign body reaction (siliconomas), secondary limphedema, tissue destruction and lethal embolism. A 35-year-old Caucasian woman came to our department with erithema and edema on the right leg, fever and chills. A thorough examination of the patient's history revealed injection of liquid silicone 7 years before for cosmetic volume increase of both legs. A closer observation revealed a small fistulous element from which came out white yellow puruloid material. Antibiotic therapy and drainage of the abscess were undertaken. Within few days of treatment erithema and swelling essentially improved and the patient was discharged. After two months she came back to our department due to the same disease on her left leg that we treated with the therapy previously used. We highlight the long time, 7 years, elapsed between liquid silicone injection and onset of cutaneous symptoms. PMID- 24217839 TI - Urrets- Zavalia Syndrome after glaucoma filtration device implantation. AB - We report a case of Urrets-Zavalia Syndrome after a glaucoma filtration device (g.f.d.) implantation. A 74-year-old woman with bilateral advanced glaucoma has been planned for surgery. The patient underwent to g.f.d. implantation in the right eye. On postoperative day 1, the patient had an edematous cornea with a dilated and non reactive pupil. In this article we describe the clinical history of this patient. To our knowledge, this is the first case of Urrets-Zavalia Syndrome after a g.f.d. implantation. PMID- 24217840 TI - Abdominal emergency in elderly: a case of small bowel obstruction and ischemia caused by bulky IA ovarian cancer. AB - Bowel obstruction resulting from colorectal and ovarian cancer is a serious and distressing complication of these malignancies. This may be caused by diffuse peritoneal carcinomatosis, bulky masses filling the pelvis and abdomen or postoperative adhesions, and should be carefully worked out by pre-operative imaging. We report the case of a small bowel obstruction and intestinal ischemia caused by a bulky (20x40 cm in diameter) cystic ovarian neoplasm that was found to be a stage IA G2 cystadenocarcinoma, successfully managed by uterus-sparing surgery. PMID- 24217841 TI - Marked elevation of transaminases and pancreatic enzymes in severe malnourished male with eating disorder. AB - We report a case of a 45 year old Caucasian malnourished male with an history of eating disorder who developed severe liver and pancreatic damage and multiorgan disfunction. At admission to our department, his body mass index (BMI) was 11.1. Biochemical evaluation showed elevated serum levels of transaminases (AST= 2291 U/L, ALT= 1792 U/L), amylase (3620 U/L), lipase (4102 U/L), CPK= 1370 U/L, LDH= 2082 U/L. No other cause of acute liver and pancreatic damage was evidenced. Haematological disorders (anemia, thrombocytopenia, leukopenia) found on admission seem related to bone marrow hypoplasia and to gelatinous marrow transformation described in severe state of malnutrition. Although a moderate increase in liver and pancreatic enzymes are a common finding in malnourished patients, only a small number of reports describes severe liver injury and multiorgan dysfunction. After a few days of treatment (hydration and nutritional support) a marked decrease of serum transaminases, lipase, amylase, CPK, LDH occurred, despite a transient increase in these levels secondary to refeeding syndrome. The association of chronic malnutrition and a decrease in systemic perfusion may be responsible for multiorgan dysfunction. In our patient the high levels of transaminases and pancreatic enzymes were the most important biochemical abnormalities normalized after refeeding. PMID- 24217842 TI - Hepatitis C virus infection and type 2 diabetes. AB - Hepatitis C virus (HCV) infection and Type 2 diabetes mellitus (T2DM) are two worldwide, major public health problems with increasing complication and mortality rates. Many epidemiological studies have demonstrated the significant association between T2DM and chronic HCV infection. In this paper we have reviewed the increasing evidence linking HCV infection and DM in more than one field (epidemiology, pathogenesis, clinical aspects, prevention and treatment). We have considered T2DM, acute and chronic HCV infection, and cirrhotic patients. Moreover, we have considered some particular populations, solid organ transplant recipients or HCV/human immunodeficiency virus (HIV) coinfected patients. In the final part we have analyzed the potential effect of the association between HCV infection and the development of DM in term of outcome and possibilities for prevention and treatment. PMID- 24217843 TI - New therapies in common ocular surface disorders. AB - Lacrimal dysfunction syndrome (LDS) and meibomian gland dysfunction (MGD) are common pathologies of the ocular surface both characterized by quantitative and/or qualitative tear film changings. They may result in symptoms of eye irritation, clinically apparent inflammation and ocular surface disease. Recent researches about the chronic inflammatory nature of dry eye, revealed the possibility to develop new treatments for LDS like new immunological drugs. MGD, alone or if it occurs contemporary to LDS, can be treated with a thermal pulsation system, a useful tool to alleviate symptoms. PMID- 24217844 TI - Biological therapies in rheumatic diseases. AB - The development of the biological drugs has revolutionized the therapeutic approach of the chronic inflammatory rheumatic diseases, particularly in patients resistant to standard treatment. These drugs are characterized by an innovative mechanism of action, based on the targeted inhibition of specific molecular or cellular targets directly involved in the pathogenesis of the diseases: pro inflammatory cytokines (tumor necrosis factor, interleukin-1 and 6), CTLA-4, and molecules involved in the activation, differentiation and maturation of B cells. Their use has indeed allowed for a better prognosis in several rheumatic diseases (such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus) and to obtain a clinical remission. In the present review we give an overview of the biological drugs currently available for the treatment of the rheumatic diseases, analyzing the different mechanism of action, the therapeutic indications and efficacy data, and adverse events. PMID- 24217845 TI - Environmental tobacco smoke: health policy and focus on Italian legislation. AB - Worldwide tobacco smoking kills nearly 6 million people each year, including more than 600,000 non-smokers who die from smoke exposure. Environmental tobacco smoke (ETS, also called secondhand smoke, involuntary smoke, or passive smoke) is the combination of sidestream smoke, the smoke given off by a burning tobacco product and mainstream smoke, the smoke exhaled by smokers. People may be exposed to ETS in homes, cars, workplaces, and public places, such as bars, restaurants, and recreational settings. In addition, there is another type of smoke which until now has not been recognized: the so-called thirdhand smoke, that comes from the reaction of mainstream smoke and environmental nitrous acid (HNO2) making carcinogenic tobacco-specific nitrosamines (TSNAs). The effects of ETS on human health are well-known, passive smoking is harmful to those who breathe the toxins and it is a serious problem for public health. The smoking ban in Italy had reduced ETS pollution, as in the United States and in other countries all over the world. However, the implementation of comprehensive legislation on smoking policy will necessitate other tobacco control measures for its successful fulfillment: increased media awareness, telephone smoking cessation helplines and smoking cessation support services could be an opportunity to ensure awareness, comprehension and support to those who want to quit smoking. The effectiveness of legislative efforts will also depend on successful enforcement of smoking bans and compliance with the legislation. This review summarizes the evidences about the effect of ETS and provides an overview of smoke-free laws and policies. PMID- 24217846 TI - Hepatitis C virus and type 1 diabetes. AB - Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms. PMID- 24217847 TI - [Albrecht von Haller: an encyclopaedic cosmopolite in the history of Swiss medicine]. AB - Albrecht von Haller was born in Bern on October 16, 1708 and studied medicine in Tubingen and Leiden. From the middles thirties on, and for seventeen years, he taught botany, anatomy and surgery at the University of Gottingen, where he founded the botanical garden, the institute of anatomy and the Royal Society of Science. His research included the study of Swiss flora, experimentation in human physiology and the investigation of vascular anatomy. One of his main scientific interests was how the human body functions, and he believed that it worked as an active organism characterized by its capacity for reaction to stimuli and impulses. In his work Icones anatomicae (1743-1756), von Haller minutely described the human arterial circulation. This scientist also investigated the properties of the nervous and muscular systems, in particular in terms of sensibility and irritability, and the development of embryos. Albrecht von Haller died in Bern on December 12, 1777. PMID- 24217848 TI - Effects of low intensity static magnetic field on FTIR spectra and ROS production in SH-SY5Y neuronal-like cells. AB - Biological effects of man-made electromagnetic fields (EMFs) have been studied so far by experimental approaches exposing animals and cell cultures to EMFs. However, the evidence for cell toxicity induced by static magnetic field (SMF) is still uncertain. We investigated the effects produced by the exposure of human SH SY5Y neuronal-like cells to a uniform magnetic field at intensities of 2.2 mT, which is less than the recommended public exposure limits set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). A decrease of membrane mitochondrial potential up to 30% was measured after 24 h of exposure to SMF in SH-SY5Y cells, and this effect was associated with reactive oxygen species production increase. Fourier transform infrared spectroscopy (FTIR) analysis showed that exposure to a static magnetic intensity around 2.2 mT changed the secondary structure of cellular proteins and lipid components. The vibration bands relative to the methylene group increased significantly after 4 h of exposure, whereas further exposure up to 24 h produced evident shifts of amide I and II modes and a relative increase in beta-sheet contents with respect to alpha-helix components. Our study demonstrated that a moderate SMF causes alteration in cell homeostasis, as indicated by FTIR spectroscopy observations of changes in protein structures that are part of cell response to magnetic field exposure. PMID- 24217850 TI - Analysis of the characteristics of interconsultations performed by emergency physicians to other hospital specialists and their evolution over time. AB - OBJECTIVE: The objective of this study was to describe the type of interconsultations carried out in the Emergency Department (ED) to hospital specialists and analyze their pattern over time. METHODS: The study was carried out during the period from 2006 to 2012. It was carried out at EDs attending to all types of interconsultations except pediatrics and obstetrics-gynecology. There were no changes in physical structure, number of personnel, or organization during the study period. The main measurements taken were as follows: monthly ED census, number of interconsultations and specialties consulted, main reason for presentation at the ED during the first (2006) and last year (2012), and, for specialties demonstrating substantial quantitative changes, main reasons for the interconsultation from the ED at the beginning (2006) and the end (2012) of the study. Linear regression analysis was carried out for the relationship between time and number of interconsultations. RESULTS: A total of 628 256 care interventions were carried out, with 128 008 interconsultations (20.4%). Orthopedic surgery and traumatology, psychiatry, and general and digestive surgery were the departments most frequently consulted (54.5% of the interconsultations). Consultations significantly reduced over time (R=0.29; P<0.001) but the percentage of interconsultations (related to ED census) remained unchanged (R=0.01; P=0.49). The behavior related to specialties was heterogeneous: consultations to general and digestive surgery, hematology and hemostasis, and urology specialists decreased, whereas to thoracic surgery, angiology and vascular surgery, neurology, nephrology, neurosurgery, psychiatry, orthopedic surgery and traumatology, and critical care medicine specialists increased. Some of the reasons for specialist consultation also significantly changed over time. CONCLUSION: The study of interconsultations allows us to identify areas of lesser autonomy of emergency physicians. Changes in the pattern of these interconsultations over time may reflect both learning processes and changes in the healthcare circuits in the ED. PMID- 24217849 TI - Evidence for a fixed capacity limit in attending multiple locations. AB - A classic question concerns whether humans can attend multiple locations or objects at once. Although it is generally agreed that the answer to this question is "yes," the limits on this ability are subject to extensive debate. According to one view, attentional resources can be flexibly allocated to a variable number of locations, with an inverse relationship between the number of selected locations and the quality of information processing at each location. Alternatively, these resources might be quantized in a "discrete" fashion that enables concurrent access to a small number of locations. Here, we report a series of experiments comparing these alternatives. In each experiment, we cued participants to attend a variable number of spatial locations and asked them to report the orientation of a single, briefly presented target. In all experiments, participants' orientation report errors were well-described by a model that assumes a fixed upper limit in the number of locations that can be attended. Conversely, report errors were poorly described by a flexible-resource model that assumes no fixed limit on the number of locations that can be attended. Critically, we showed that these discrete limits were predicted by cue-evoked neural activity elicited before the onset of the target array, suggesting that performance was limited by selection processes that began prior to subsequent encoding and memory storage. Together, these findings constitute novel evidence supporting the hypothesis that human observers can attend only a small number of discrete locations at an instant. PMID- 24217851 TI - Variation in size of blood puddles on different surfaces. AB - OBJECTIVE: It is known that visual estimation of blood loss is inaccurate independently from experience and qualification of rescuers or members of hospital staff. There is no information available about the size of a puddle of blood for a given amount of blood depending on the surface. This pilot study evaluated the size of blood puddles on various surfaces. METHODS: Human blood was portioned in standardized amounts of fluid and poured on different surfaces: wooden and polyvinyl chloride (PVC) floors, flagging, carpet, asphalt, concrete, forest soil, mattress and towel. The resulting puddles of blood were documented by digital photos and their surface areas measured using a computer. RESULTS: The largest blood puddles were found on even surfaces such as PVC floors and concrete, and the smallest blood puddles were found on forest soil and carpet. When blood volume was 100 ml, the difference between the smallest and the largest blood puddle added up to a factor of 13.8 (77 cm forest soil, 1061 cm PVC). This factor was comparable in all other blood amounts on these two surfaces (13.7 with 250 ml, 13.0 with 500 ml, 13.5 with 1000 ml). A table with objects of daily life of comparable size (CD, letter, newspaper, etc.) was added for teaching purposes. CONCLUSION: The size of puddles of blood depended strongly on the type of surface. Up to 13 times larger blood puddles were found on hard and nonabsorbant surfaces (PVC, concrete) than on absorbant surfaces such as carpet or forest soil. PMID- 24217852 TI - Bilateral eye irrigation: a simple and effective hands-free technique. AB - Bilateral chemical eye injuries are a common and important problem in the Emergency Department. Irrigation of both eyes can be time-consuming, so we present a novel, simple and cost-effective technique for hands-free bilateral eye irrigation. Modifications of a generic dual-lumen cannula adapter and fixation about the glabella allow sterile irrigation fluid to be delivered directly to the medial canthi of the contaminated eyes in a hands-free fashion. Our customized rig frees both the clinician(s) and patient, thus conferring benefits to both. Patients regain autonomy of movement to reposition themselves for comfort or to manipulate the eyelids for more effective irrigation. Clinicians are freed to tend to other tasks. By sharing this technique we hope to stimulate discussion on the safest and most effective method of irrigating chemically injured eyes and prompt the generation of comparable outcome data for the benefit of patients. PMID- 24217853 TI - Organ donation after circulatory death: an update. AB - There is an ongoing shortfall of organs for donation in the UK and worldwide. Strategies including donation after circulatory death (DCD), living donation and better identification of potential donors are attempting to increase the number of donors and donated organs. The number of DCD donors in the UK increased by 808% from 37 to 336 between 2001 and 2010 and this is continuing to increase. The most common organs donated from DCD donors are the kidneys, but there is increasing experience of liver, lung and pancreas transplantation. The process of DCD varies between different countries and institutions. The outcome of DCD transplantation has been largely encouraging, particularly for kidneys. The increase in DCD has led to an appraisal of issues that may arise during the donation process; these include the Lazarus phenomenon, the dead donor rule, perimortem interventions, public opinion and conflict of interest for clinicians. PMID- 24217854 TI - [Neuropathic pain: pathophysiology, assessment, and therapy]. AB - Neuropathic pain is caused by lesions in the somatosensory system. Characteristic but not exclusive features are spontaneous burning pain, electrifying and shooting pain, hyperalgesia, and allodynia. The basic concept of the pathophysiology of neuropathic pain is the combination of peripheral and central sensitization. Knowledge on the molecular mechanisms has grown exponentially in recent years. The problem lies in identifying the individual mechanisms and in determining a comprehensive concept. Progress has also been made in assessment, e.g., methods for detecting dysfunction of nociceptors have significantly improved. In addition, there are many more therapeutic options available than 15 years ago. The drugs available include antidepressants, anticonvulsants, opioids, and topical medications. Data from controlled trials and recommendations from guidelines are available. PMID- 24217855 TI - Dynamic social networks in recovery homes. AB - Acute treatment aftercare in the form of sober living environments-i.e., recovery houses-provide an inexpensive and effective medium-term treatment alternative for many with substance use disorders. Limited evidence suggests that house-situated social relationships and associated social support are critical determinants of how successful these residential experiences are for their members, but little is known about the mechanisms underlying these relationships. This study explored the feasibility of using dynamic social network modeling to understand house situated longitudinal associations among individual Alcoholics Anonymous related recovery behaviors, length of residence, dyadic interpersonal trust, and dyadic confidant relationship formation processes. Trust and confidant relationships were measured 3 months apart in U.S. urban-area recovery houses, all of which were part of a network of substance use recovery homes. A stochastic actor-based model was successfully estimated from this data set. Results suggest that confidant relationships are predicted by trust, while trust is affected by recovery behaviors and length of residence. Conceptualizing recovery houses as a set of independent, evolving social networks that can be modeled jointly appears to be a promising direction for research. PMID- 24217856 TI - A rhodamine-based "turn-on" fluorescent probe for Fe3+ in aqueous solution. AB - A water-soluble "turn-on" fluorescent probe (RD1) for Fe(3+) based on rhodamine B was designed and synthesized. The fluorescent probe showed "turn-on" fluorescent and colorimetric responses to Fe(3+) with a high selectivity in water containing less than 1% organic cosolvent. Furthermore, bioimaging investigations indicated that the new probe was cell permeable and suitable for monitoring intracellular Fe(3+) in living cells by confocal microscopy with low cytotoxicity. PMID- 24217857 TI - 5,10-Diacylcalix[4]pyrroles: synthesis and anion binding studies. AB - 5,10-Diacylcalix[4]pyrrole, a new positional isomer of the recently reported 5,15 diacylcalix[4]pyrrole, is synthesized as its two configurational isomers by acid catalysed condensation of meso-diacyltripyrrane with pyrrole. The solution phase anion binding of the two isomers of 5,10-diacylcalix[4]pyrrole was investigated by (1)H NMR spectroscopy in chloroform-d and isothermal titration calorimetry (ITC) in acetonitrile to gain insights into the positional and conformational effects of substituents on the macrocycle periphery towards anion binding. During the investigation, a functionalized, stable pyrrole-2-carbinol was isolated and subsequently converted to the corresponding tripyrrane in situ. PMID- 24217858 TI - Uraemic pruritus markedly affects the quality of life and depressive symptoms in haemodialysis patients with end-stage renal disease. AB - Little is known about the influence of uraemic pruritus on patients' wellbeing. The aim of our study was to evaluate the impact of uraemic pruritus on quality of life and depressive symptoms in patients with end-stage renal disease. A total of 200 haemodialysis patients were included into the study. The prevalence of uraemic pruritus was 38%. Patients with uraemic pruritus had significantly lower quality of life according to SF-36 questionnaire compared to the remaining of analysed subjects. Among patients with uraemic pruritus, 64.5% individuals also showed impaired skin-related quality of life evaluated with Dermatology Life Quality Index. The quality of life impairment correlated with uraemic pruritus intensity assessed with VAS and the 4-item itch questionnaire. Depression level significantly correlated with quality of life and severity of depressive symptoms was significantly associated with uraemic pruritus intensity. Our study underscores that uraemic pruritus should be regarded as an important health problem among haemodialysis patients. PMID- 24217860 TI - Discrepancy between functional exercise capacity and daily physical activity: a cross-sectional study in patients with mild to moderate COPD. AB - BACKGROUND: In patients with moderate to severe chronic obstructive pulmonary disease (COPD) the six-minute walk distance reflects the functional exercise level for daily physical activity. It is unknown if this also applies to patients with mild to moderate COPD in primary care. AIMS: To assess the relationship between functional exercise capacity and physical activity in patients with mild to moderate COPD. METHODS: A cross-sectional study was performed in 51 patients with mild to moderate COPD in primary care. Functional exercise capacity was assessed by the six-minute walk test and physical activity was measured with an accelerometer-based activity monitor. RESULTS: Functional exercise capacity was close to normal values. However, the daily physical activity of the patients could be classified as 'sedentary' and 'low active'. No significant correlations were observed between six-minute walk distance (% predicted) and any of the physical activity variables (steps per day, movement intensity during walking, total active time, total walking time, physical activity level, and time spent in moderate physical activity). CONCLUSIONS: A discrepancy was found between functional exercise capacity and daily physical activity in patients with mild to moderate COPD recruited and assessed in primary care. We conclude that these variables represent two different concepts. Our results reinforce the importance of measuring daily physical activity in order to fine-tune treatment (i.e. focusing on enhancement of exercise capacity or behavioural change, or both). PMID- 24217859 TI - Continuing discrepancy between patient perception of asthma control and real world symptoms: a quantitative online survey of 1,083 adults with asthma from the UK. AB - BACKGROUND: Previous studies have identified a discrepancy between patient perception of asthma control and real-world symptoms; despite several hypotheses, the reasons remain unclear. AIMS: To explore patients' experiences of asthma symptoms and disease management and their educational needs in the UK; to assess recent progress in asthma control and management. METHODS: A quantitative questionnaire-based online survey of UK patients aged >18 years with self reported asthma. RESULTS: Of the 1,083 individuals (55% female, 49% aged >55 years) who completed the survey, 79% described their asthma control as 'good' or 'very good'. Despite this, in the previous 2 years, 65% had experienced 'frequent' day-time symptoms, 37% had 'frequent' night-time symptoms, and 25% had used oral steroids for asthma; 41% of those prescribed a reliever inhaler used it >1 a day. Overall, 76% had a 'good' or 'very good' relationship with their healthcare professional (HCP); 32% had not attended regular asthma reviews and only 12% were using a personal asthma action plan. Moreover, 70% of respondents felt that they had the 'main responsibility' for managing their asthma; 29% believed this responsibility to be shared with their HCP. CONCLUSIONS: This survey indicates a continuing discrepancy between patient perception of asthma control and real-world symptoms, with little change from previous studies. Many patients accept symptoms as the norm. The diversity among respondents' attitudes demonstrates a need to help patients change some of their beliefs and understanding about asthma, and to improve asthma management with better education about the understanding of control for patients and HCPs. PMID- 24217862 TI - Abnormalities of autobiographical memory of patients with depressive disorders: a meta-analysis. AB - BACKGROUND: Previous studies on the autobiographical memory (AM) of depressed patients had inconsistent findings. Various severities of depression in patients in these studies may lead to conflicting results. However, the differences in the procedure of the autobiographical memory tests (AMTs) may also influence the AM results. OBJECTIVE: In this study, we analyse the results published so far to research the AM characteristics of patients with depressive disorders and identify moderators that affect the assessment results while using AMT in this field. METHOD: A systematic search was conducted using following databases: MEDLINE, PubMed, ScienceDirect, Cnki, and Google Scholar, yielding 22 studies of patients with depressive disorders and autobiographical memory published between 1986 and 2010. RESULTS: The results of meta-analysis showed that, compared with the control group, the patients with depressive disorders reported less specific AMs (g = -1.051) and more overgeneralized AMs (g = 1.115). The patients with depressive disorders also recalled more slowly (g = 0.400). The effect sizes of overgeneral memory could be predicted by the self-reported depression score of the depressed patients (B = -.329, p < .01). The mean effect sizes of AMT indices were affected by the AMT characteristics (i.e., number of cue word, max response time, prompting, presentation of cue word, taping, and so on). CONCLUSIONS: Our results suggest that overgeneralization and response lag are the AM deficits in patients with depressive disorders. The parameters of AMT are important factors, which are related to the inconsistency in the assessment of AM in patients with depressive disorders. Some recommendations on AMT and programme research design are given for future research. PMID- 24217861 TI - Spanish multicenter normative studies (NEURONORMA project): normative data and equivalence of four BNT short-form versions. AB - The application of the Boston Naming Test (BNT) is time-consuming and shortened versions need to be developed for screening purposes. The aims of this study were to develop four equivalent 15-item forms of a Spanish adaptation of the BNT, to test the equivalence of the new versions in a clinical sample, and to provide normative data. The normative sample consisted of 340 subjects. The clinical sample included 172 patients (76 Mild Cognitive Impairment and 96 Alzheimer's disease). An empirical procedure was used to develop the shortened versions. All new versions demonstrated satisfactory internal consistency. Pearson's coefficient analysis showed strong relationships among the four short-form versions as well as between each of them and the 60-item test. The inferential confidence interval method demonstrated the equivalence between the four shortened versions. Age and education affected the score of all short-form versions, but sex was found to be unrelated to the performance. Normative data were calculated for midpoint age groups. This paper proposes four 15-item equivalent versions that could be useful and time-saving tools for screening purposes. PMID- 24217863 TI - Expressive writing, self-criticism, and self-reassurance. AB - OBJECTIVES: Self-criticism and reassurance are important mechanisms for regulating negative emotions but relatively little attention has been paid to interventions aimed at improving them. DESIGN: This study explored the use of an expressive writing task to increase self-reassurance and reduce self-criticism using a randomized controlled design. METHOD: A total of 46 participants wrote either about life goals (the expressive writing task, n= 23) or a control topic (a review of a recent book or film, n= 23) for 15 min, three times within an hour. Measures of self-criticism/self-reassurance, stress, and positive affect were completed at baseline and at 2-week follow-up. The Linguistic Inquiry and Word Count (LIWC) was used to analyse the writing of participants in the 'life goals' condition to identify psychological processes that might differentiate those who improved and those who did not. RESULTS: While there were no significant changes in self-reported stress or positive affect, participants writing about life goals decreased in their levels of self-criticism at 2-week follow-up relative to participants writing about control topics. Text analysis showed that experimental participants using words that imply the possibility of doubt or failure, including use of the subjunctive tense (e.g., could, would, should), were least likely to decrease their self-criticism. CONCLUSION. Expressive writing shows promise as a means by which people may decrease in their self-criticism. Future research should determine whether such experimentally induced changes in self-criticism lead to the improvements in psychological health that is implied by previous cross-sectional research. PMID- 24217864 TI - An exploration of group compassion-focused therapy for personality disorder. AB - BACKGROUND: People with personality disorders, especially those who also experience high self-criticism and shame, are known to be a therapeutic challenge and there is a high dropout rate from therapy. Compassion-focused therapy (CFT) was designed to address shame and self-criticism specifically, and to develop people's ability to be self-reassuring and more compassionate to themselves and others. AIMS: This study explored how CFT affected self-criticism and self attacking thoughts, feelings, and behaviours, as well as the general symptoms of anxiety, stress, and depression of a personality disordered group within an outpatient group setting, and evaluated the extent of maintenance at a 1-year follow-up. A secondary objective was to identify some of the key characteristics that such an intervention would require. This was a pilot study exploring the feasibility, acceptability, and potential value of CFT in treating this difficult population and, as such, was designed as a pre-randomized controlled trial (RCT) to provide evidence to support applications for funding for an RCT. METHODS AND DESIGN: This study utilized a mixed method combining qualitative and quantitative methods to support a programme evaluation. Eight participants were introduced to the evolutionary-based CFT model and taken through explorations of the nature of self-criticism and shame. In subsequent sessions, participants were taught the main compassion-focused exercises, and any difficulties were addressed. The group was asked to share their personal stories and experiences of practicing self compassion and to develop compassionate encouragement for each other. Self-report measures were administered at the beginning, end, and at a 1-year follow-up. RESULTS: This 16-week group therapy was associated with significant reductions in shame measured by the Others as Shamer Scale (OAS), social comparison on the Social Comparison Scale (SCS) feelings of hating oneself, and an increase in abilities to be self-reassuring on the Self-Attacking and Self-Reassuring Scale (FSCRS), depression and stress measured by the Depression Anxiety and Stress Scale (DASS). There were significant changes on all CORE variables, well-being, risk, functioning, and problems. Also interesting was that all variables showed a trend for continued improvement at 1-year follow-up, albeit statistically non significant. A content analysis revealed that patients had found it a moving and very significant process in their efforts to develop emotional regulation and self-understanding. CONCLUSION: CFT, delivered in a routine psychotherapy department for personality disorders, revealed a beneficial impact on a range of outcome measures. These improvements were maintained and further changes noted at 1-year follow-up. Further research is needed to explore the benefits of CFT using more detailed analysis and RCTs. PMID- 24217865 TI - Impulsivity and risk for mania: towards greater specificity. AB - BACKGROUND: Impulsivity is elevated among people diagnosed with bipolar disorder, and recent evidence suggests that impulsivity can predict onset among those at risk for the disorder. Impulsivity, though, is a broad construct. OBJECTIVE: The goal of this study was to examine whether some aspects of impulsivity are more correlated with risk for mania than others. We hypothesized that risk for mania would be related specifically to difficulties controlling impulsive responses to emotions. DESIGN AND METHODS: Undergraduates (N = 257) completed a large battery of measures of emotion-relevant and non-emotional forms of impulsivity, along with a well-validated measure of risk for mania, the Hypomanic Personality Scale (HPS). RESULTS: Analyses examined correlations of impulsivity scales with the HPS, and partial correlations controlling for lifetime tendencies towards depressive symptoms and current symptoms of alcohol abuse, both of which relate to impulsivity and often co-occur with mania. After controlling for these measures, risk for mania remained correlated with measures of impulsive responses to positive emotions, but not with difficulties in following through or with impulsivity in the context of general distress emotions. CONCLUSIONS: Although impulsivity is a major concern among those at risk for mania and those diagnosed with mania, difficulties may be especially evident during positive affective states, and other forms of impulsivity may be less related to mania risk. Discussion focuses on limitations and future directions. PRACTITIONER POINTS: Impulsivity is correlated with risk for mania. Mania risk appears tied to tendencies towards impulsive action, particularly during positive affective states. Mania risk was not significantly correlated with other non-emotional forms of impulsivity. A better understanding of what aspects of impulsivity are problematic in bipolar disorder could guide more refined interventions. PMID- 24217866 TI - Relationship between attributional style, perceived control, self-esteem, and depressive mood in a nonclinical sample: a structural equation-modelling approach. AB - BACKGROUND: The aim of this study was to examine the intricate relationship between some personality traits (i.e., attributional style, perceived control over consequences, self-esteem), and depressive mood in a nonclinical sample (N= 334). Method. Structural equation modelling was used to estimate five competing models: two vulnerability models describing the effects of personality traits on depressive mood, one scar model describing the effects of depression on personality traits, a mixed model describing the effects of attributional style and perceived control over consequences on depressive mood, which in turn affects self-esteem, and a reciprocal model which is a non-recursive version of the mixed model that specifies bidirectional effects between depressive mood and self esteem. RESULTS: The best-fitting model was the mixed model. Moreover, we observed a significant negative effect of depression on self-esteem, but no effect in the opposite direction. CONCLUSIONS: These findings provide supporting arguments against the continuum model of the relationship between self-esteem and depression, and lend substantial support to the scar model, which claims that depressive mood damages and erodes self-esteem. In addition, the 'depressogenic' nature of the pessimistic attributional style, and the 'antidepressant' nature of perceived control over consequences plead in favour of the vulnerability model. PMID- 24217867 TI - High and happy? Exploring the experience of positive states of mind in people who have been given a diagnosis of bipolar disorder. AB - OBJECTIVES: To approach the experience of 'happiness' and 'mania' for people who have been given a diagnosis of 'bipolar disorder' and to explore how they might differentiate or associate between these experiences. DESIGN: A qualitative design was used in which four participants who had been given a diagnosis of 'bipolar disorder' were interviewed individually regarding their experiences and ideas about 'mania' and 'happiness'. METHODS: Transcriptions from the interviews were analysed using the iterative process of interpretative phenomenological analysis. RESULTS: Four superordinate themes were identified. Two highlighted the conceptual fluidity and similarities between their ideas about and experiences of 'happiness' and 'mania'. Two emphasized the differences between these notions for the participants, which reflected the destruction, disruption, and chaos of 'mania' in contrast to the importance of self-acceptance, peacefulness, and social connection for 'happiness'. CONCLUSION: There may be benefit in maintaining an active dialogue or 'poly-vocality' about the meanings of 'happiness' in clinical work with people who experience 'positive states' of mind, which are personally problematic. This can be supported by drawing on ideas and narratives about 'happiness' from the field of positive psychology. PMID- 24217868 TI - Systemic family psychotherapy in China: a qualitative analysis of therapy process. AB - OBJECTIVES: Although the procedure of systemic family therapy has been extensively researched in Western culture, few studies on this subject have been conducted in China. The aim of this study was to specify the therapy-delivered interventions in Chinese systemic family therapy and to explore how Western imported systemic therapy model is delivered in Chinese culture. DESIGN: A qualitative and exploratory research approach was taken in which thematic analysis was used to analyse the transcribed psychotherapy videotapes with Chinese families. METHODS: Twenty-six hours of video-recorded systemic family therapy sessions from 14 Chinese family cases were sampled. Thematic analysis was used to analyse the transcriptions of therapy sessions and identify therapist generated interventions in therapy. Frequencies of different interventions were counted, and correspondence analysis (CA) was used to reveal the corresponding relationships between different interventions. RESULTS: Analysis led to two main themes related to therapists-delivered interventions: Therapist's intention and therapy technique. Results revealed 15 types of therapist's intentions and 16 categories of therapy techniques. CA indicated that therapists' intentions changed across different therapy stages and specific techniques were used to achieve corresponding intentions. CONCLUSIONS: Interventions delivered in Chinese systemic therapy are mainly adherent with Milan and post-Milan systemic models. Due to the shortage in systemic therapy service in China and Chinese culture advocating reverence to authority, components of psycho-education, guidance, and metaphor are adopted in Chinese systemic practice. Some directions for future research are suggested. PMID- 24217869 TI - Cell culture monitoring for drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem. AB - We present a novel, multiparametric microphysiometry system for the dynamic online monitoring of human cancer cell metabolism. The optically transparent, modular, hybrid microsystem is based on a glass chip and combines a cell cultivation chamber, microfluidics and metabolic monitoring with fully integrated chemo- and biosensors. pH and oxygen are measured in the cell culture area, and biosensors for lactate and glucose are connected downstream by microfluidics. The wafer-level fabrication features thin-film platinum and iridium oxide microelectrodes on a glass chip, microfluidics in an epoxy resist, a hybrid assembly and an on-chip reference electrode. The reliable analytical performance of the sensors in cell culture medium was demonstrated. The pH sensors exhibit a long-term stable, linear response. The oxygen sensors show a linear behaviour, which is also observed for low oxygen concentrations. Glucose and lactate measurements show a linear, long-term stable, selective and reversible behaviour in the desired range. T98G human brain cancer cells were cultivated and cell culture metabolism was measured on-chip. Stop/flow cycles were applied and extracellular acidification, respiration, glucose consumption and lactate production were quantified. Long-term metabolic rates were determined and all parameters could be measured in the outlet channel. A placement downstream of the cell cultivation area for biosensors was realised. A highly effective medium exchange and undiluted sampling from the cell culture chamber with low flow rates (2 MUl min(-1)) and low volumes (15 MUl per cycle) were achieved. The drug screening application was demonstrated by detecting alteration and recovery effects of cellular metabolism induced by the addition of substances to the medium. PMID- 24217870 TI - What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib? AB - The introduction of imatinib to clinical practice revolutionized therapy of advanced gastrointestinal stromal tumors (GIST), but its long-term results have been only just collected. We have attempted to identify factors related to the long-term survival. We have analyzed the data of 430 inoperable/metastatic/recurrent GIST patients treated with imatinib in reference centers, assessed the factors influencing the long-term overall survival (OS), and compared the outcomes in three periods of initiation of imatinib therapy during one decade (2001-2003, 2004-2006, 2007-2010). During analyzed time periods, we have found decrease in median largest tumor size at the start of imatinib therapy: 90.5 mm (2001-2003) versus 74 mm (2004-2006) versus 58 mm (2007 2010) (p = 0.002). Median progression-free survival (PFS) on 1st line imatinib was 37.5 months, without differences in PFS between three groups. Median OS was 5.8 years, 8-year OS rate was 43%, and no difference in OS was demonstrated for patients treated in analyzed time periods. Independent good prognostic factors for longer OS were as follows: surgery of residual disease, initial WHO performance status 0/1, normal baseline albumin level, and the presence of exon 11 KIT mutations. Current median OS in advanced GIST reaches 6 years. The long term survivors were characterized by smaller maximal tumors at imatinib start, better blood tests results, better performance status, and the surgical removal of residual disease. The latter might reduce the impact of tumor size and equalize the long-term results of therapy during last decade from introduction of imatinib. After introduction of subsequent lines of therapy (as sunitinib), the effect of primary mutational status on the long-term OS is also less visible. PMID- 24217872 TI - Extracellular expression of glucose inhibition-resistant Cellulomonas flavigena PN-120 beta-glucosidase by a diploid strain of Saccharomyces cerevisiae. AB - The catalytic fraction of the Cellulomonas flavigena PN-120 oligomeric beta glucosidase (BGLA) was expressed both intra- and extracellularly in a recombinant diploid of Saccharomyces cerevisiae, under limited nutrient conditions. The recombinant enzyme (BGLA15) expressed in the supernatant of a rich medium showed 582 IU/L and 99.4 IU/g dry cell, with p-nitrophenyl-beta-D-glucopyranoside as substrate. BGLA15 displayed activity against cello-oligosaccharides with 2-5 glucose monomers, demonstrating that the protein is not specific for cellobiose and that the oligomeric structure is not essential for beta-D-1,4-bond hydrolysis. Native beta-glucosidase is inhibited almost completely at 160 mM glucose, thus limiting cellobiose hydrolysis. At 200 mM glucose concentration, BGLA15 retained more than 50 % of its maximal activity, and even at 500 mM glucose concentration, more than 30 % of its activity was preserved. Due to these characteristics of BGLA15 activity, recombinant S. cerevisiae is able to utilize cellulosic materials (cello-oligosaccharides) to produce bioethanol. PMID- 24217873 TI - Diazotrophic diversity in the Caribbean coral, Montastraea cavernosa. AB - Previous research on the Caribbean coral Montastraea cavernosa reported the presence of cyanobacterial endosymbionts and nitrogen fixation in orange, but not brown, colonies. We compared the diversity of nifH gene sequences between these two color morphs at three locations in the Caribbean and found that the nifH sequences recovered from M. cavernosa were consistent with previous studies on corals where members of both the alpha-proteobacteria and cyanobacteria were recovered. A number of nifH operational taxonomic units (OTUs) were significantly more abundant in the orange compared to the brown morphs, and one specific OTU (OTU 17), a cyanobacterial nifH sequence similar to others from corals and sponges and related to the cyanobacterial genus Cyanothece, was found in all orange morphs of M. cavernosa at all locations. The nifH diversity reported here, from a community perspective, was not significantly different between orange and brown morphs of M. cavernosa. PMID- 24217871 TI - Genetic characterization of feline calicivirus strains associated with varying disease manifestations during an outbreak season in Missouri (1995-1996). AB - Feline calicivirus (FCV) is a common cause of mild to severe upper respiratory tract disease (URTD) in cats. FCV strain 21223 was isolated from a kitten with severe pneumonia in a disease outbreak with unusually high mortality (35 %) that occurred in a Missouri feline colony in 1995-1996. Phylogenetic analysis of the genome sequence of strain 21223 indicated the emergence of a new FCV strain. Analysis of the full-length genome sequence of a closely related (99.5 % nucleotide identity) strain, 3786, obtained from an asymptomatic animal in the same colony four months later, showed the presence of seven amino acid substitutions, with six of them located in the VP1 capsid sequence encoded by ORF2. Comparative analysis of the E-region sequences (426-521 aa ORF2) presumably involved in virus-host cell receptor interactions did not identify amino acid substitutions unique to the virulent strain. We determined the complete genome sequences of four virus isolates that were collected in regional catteries in the months following the outbreak that were associated with different manifestations of the disease (URTD, chronic stomatitis, and gingivitis). We show that genetically distinct FCV strains were cocirculating in the area, and no apparent correlation could be made between overall sequence and observed disease. PMID- 24217874 TI - The mannobiose-forming exo-mannanase involved in a new mannan catabolic pathway in Bacteroides fragilis. AB - We have proposed a new mannan catabolic pathway in Bacteroides fragilis NCTC 9343 that involves a putative mannanase ManA in glycoside hydrolase family 26 (BF0771), a mannobiose and/or sugar transporter (BF0773), mannobiose 2-epimerase (BF0774), and mannosylglucose phosphorylase (BF0772). If this hypothesis is correct, ManA has to generate mannobiose from mannans as the major end product. In this study, the BF0771 gene from the B. fragilis genome was cloned and expressed in Escherichia coli cells. The expressed protein was found to produce mannobiose exclusively from mannans and initially from manno-oligosaccharides. Production of 4-O-beta-D-glucopyranosyl-D-mannose or 4-O-beta-D-mannopyranosyl-D glucose from mannans was not detectable. The results indicate that this enzyme is a novel mannobiose-forming exo-mannanase, consistent with the new microbial mannan catabolic pathway we proposed. PMID- 24217875 TI - [Dog-based multi-sensorial therapy of a patient with a "persistent vegetative state"--a case report]. AB - AIM: There is evidence that animal-assisted therapy can have beneficial effects in patients with cognitive disorders. In the present case study, the influence of animal-assisted therapy was to be investigated in a patient with most severe cerebral lesions. METHODS: A 27 year old patient with a persistent vegetative state since 5 years after severe traumatic brain injury received long term treatment by 54 sessions of animal-assisted therapy. RESULTS: During the course of the therapeutic interventions, the patient showed more and more signs of vegetative, emotional and motor reactions. The latter were increasingly target bound and at last allowed a simple type of non-verbal communication. CONCLUSION: The present case indicates that animal-assisted therapy can be a reasonable option to treat patients with most severe cerebral lesions. Furthermore, the results illustrate that the usual diagnostic classification such as "persistent vegetative state" based on a neurological investigation alone may be questionable. Possible reasons for the impact of animal-assisted therapy are complex and comprise e.g. multiple sensory stimuli. PMID- 24217876 TI - [Education, advanced and further training in the field "psychology in rehabilitation"]. AB - The commission for vocational training, training and further education of the German Society of Rehabilitation Science tends to discuss and to give recommendations for various professions in rehabilitation. The working group, which is led by J. Bengel/Freiburg and M. Morfeld/Magdeburg-Stendal created an inventory of Rehabilitation Psychology. The training programs for Rehabilitation Psychology at universities and universities of applied science in Germany are based on a job profile of psychologists in medical and vocational rehabilitation. The different universities have diverse priorities focusing on Rehabilitation Psychology. The offer changes because of the adaption of requirements and implementation of Bologna Reform. The training and further education offers are specific and available for large indication areas. Finally outstanding issues and problems are pointed out. PMID- 24217877 TI - [Specific work-related problems: do they matter in access to work-related medical rehabilitation?]. AB - BACKGROUND: The study determined if need for rehabilitation in work-related medical rehabilitation (WMR) is more frequently characterised by specific work related problems than in conventional medical rehabilitation (MR). METHODS: In 6 rehabilitation centres, persons with back pain (M50, M51, M53, M54) were surveyed about work-related restrictions of work ability at begin of their rehabilitation. RESULTS: Differences in work ability of WMR and MR patients confirmed need related access. However, these differences were exclusively explained by screening-based access decisions. If access was not supported by a screening, WMR and MR patients did not differ. Decisions by rehabilitation centres compared with decisions by insurance agencies resulted in similar differences between WMR and MR patients. CONCLUSION: Screening-based decisions about access enable a more need-related access to WMR. As there were no differences between access decisions by rehabilitation centres and insurance agencies, access decisions can be realised already by the insurance agency. PMID- 24217878 TI - [Rehabilitation goals in discharge reports and in patient questionnaires--on the example of endometriosis patients]. AB - BACKGROUND: [corrected] The goal orientation of rehabilitation has increasingly found its way in research and practice. Though, shortcomings were ascertained for the implementation into the clinical routine furthermore. An empirical analysis of goal setting in clinical practice should complement the available evidence. METHODS: The study is based on a cross-sectional survey of all endometriosis patients, who had been treated at a rehabilitation center in 2008 or 2009. Data stemmed from the uniform medical rehabilitation discharge reports, and a patient questionnaire, which was sent to the registered women by the clinic routinely before the beginning of the rehabilitation. Data about rehabilita-tion goals were available as free text information for both the discharge reports as well as the pa-tient questionnaires. A category system oriented at the ICF system (International Classification of Functioning, Disability and Health), was developed to structure the goals. RESULTS: 293 patients had provided information concerning their rehabilitation goals, while 69 patients didn't reply to the question of their rehabilitation goals. The latter were excluded to the analysis. In the discharge reports, altogether, more goals were documented than in the patient questionnaires (5.98 compared to 4.97 goals per patient). In 35% of the numbers of rehabilitation goals clear congruence was found between the data in the discharge reports and the patient questionnaires. CONCLUSION: The results support the assump-tion that the included patients had difficulties in goal setting. In addition it is obvious that the goals in the discharge reports had little relation to the goals framed by the patients, in language and content. A goal-setting process less oriented towards the medical and clinical needs but more towards the patients needs and expectation would be desirable particularly with regard to a more intensive patient orientation. The implementation of a prepared list of possible rehabilitation goals could serve for the shared goal setting process in the context of anamnesis. PMID- 24217879 TI - [Proactive screening for rehabilitation need in type 2 diabetics from an AOK Disease Management Programe: which patients will be identified?]. AB - BACKGROUND: Medical rehabilitation seems suitable for implementing multimodal interventions for the treatment of type 2 diabetes. Rehabilitation in Germany on principle requires that insurees file an application. Proactive screening for rehabilitation need has only been explored in pilot projects so far. It seems a promising attempt to assess rehab need by questionnaire especially in patients with type 2 diabetes. We do not know though how patients who have been screened positive for rehab need differ from other patients with type 2 diabetes as to their health and risk profiles. This could provide an indication of the validity of the proactive approach. METHODS: Members of an Allgemeine Ortskrankenkasse (AOK) Disease Management Program (DMP) for type 2 diabetes were screened for rehab need by questionnaire. 13 diabetes-specific problem areas were assessed. Problems were assigned to 10 specific treatments (problem-treatment-pairs). Rehab need was presumed if patients needed 3 or more treatments. Patients were then compared to regular rehab patients as well as patients with type 2 diabetes from primary care medical offices. RESULTS: From 5500 DMP-patients 829 returned the questionnaire (return rate: 15.5%). From these 94% met the criteria for rehab need; of these 55% needed 6 or more treatments (complex problems). Patients who screened positive for rehab suffered from more health problems and had worse risk profiles as compared to patients from medical offices, and disease burden was comparable or worse as compared to regular rehab patients. CONCLUSIONS: This indicates that proactive screening for rehab need in patients with type 2 diabetes leads to reasonable (valid) results. The very low return rate suggests that the sample may be considerably biased, though. Possibly, mainly patients with greater impairment to health responded to the screening. PMID- 24217880 TI - [Rehabilitation of severely injured patients in acute care hospitals: who is doing what? A nationwide survey in the Trauma Network DGU]. AB - BACKGROUND: During the treatment of severely injured patients, rehabilitation takes an important role. In this study we examined the present structures in acute care hospitals, which influence the process of rehabiliation. MATERIALS AND METHODS: The data was captured in a questionnaire. The questions deal with the personal and structural situation of acute care hospitals in Germany. The questionnaires were sent to all clinics, which are registered in the TraumaNetwork DGU. RESULTS: 424 hospitals answered the questionnaire. This is a response rate of 57.3% regarding 740 acitve clinics in the TraumaNetwork DGU. 58% have no opportunity for rehabilitation. The majority of the hospitals have a physiotherapy, (98.6%) or an occupational therapy (71.0%); 33.3% have a case management. Only 17.0% of the hospitals have rehabilitation teams which take care during the hospital stay. These teams consist mainly of internal rehabilitation physicians and physical therapists. Supraregional Trauma Center have better organized structures, as hospitals with lower level of care. Only 56.6% of all hospitals reported that they were familiar with the cooperating rehabilitation hospitals. There are special cooperations with rehabilita-tion hospitals in 34.4% of all cases. CONCLUSION: The early mobilisation of severely injured patients is an integral part of the postoperative course in German hospitals. While on the one hand a large number of hospitals have good structural conditions on the other hand these structures are little integrated in the daily treamtment. There are major gaps and uncertainties in the cooperation between acute care clincs and rehabilitation hospitals. The integra-tion of rehabilitation hospitals in the TraumaNetwork DGU could be a good chance to improve this collaboration. PMID- 24217881 TI - [Data analysis based on the Classification of Therapeutic Procedures (CTL) of inpatient rehabilitation of depressive disorders]. AB - OBJECTIVE: As an initiative of the German Pension Insurance Association (DRV), evidence-based therapeutic modules (ETM) for the rehabilitation of patients with depression were developed. The objective of the subsequent analysis was to analyse the therapeutic procedures in inpatient rehabilitation on the basis of the ETM to evaluate the principal needs for therapeutic standards. METHODS: Data based on the German Classification of Therapeutic Procedures (KTL) for 21 529 patients treated in rehabilitation clinics for people with mental illnesses was analysed with respect to differences between diagnostic groups/clinics regarding type, quantity and duration of measures coded. RESULTS: The mean quantity and duration of the interventions for patients with depressive disorders encoded varied greatly between the ETM. No or only minor differences were found between patients with depression and those with other diagnoses regarding the type, quantity and duration of measures coded. However, there were great variances between clinics. CONCLUSIONS: Therapeutic standards for rehabilitative practice appear necessary in order to reduce treatment heterogeneity between rehabilitation facilities, which could improve the quality of healthcare. PMID- 24217882 TI - [Resources and self-management skills in multiple sclerosis patients - can the scale structure of the questionnaire FERUS be replicated?]. AB - BACKGROUND: To assess resources and self-management skills the generic questionnaire FERUS was developed by Jack (2007) and validated and standardized in a sample of psychosomatic patients and of healthy people. The aim of this study was the psychometric review of the FERUS with a sample of patients with Multiple Sclerosis (MS). METHODS: The dimensional structure identified by Jack was replicated in an exploratory factor analyses as well as tested in a confirmatory factor analyses and the discrimination ability of the scales was examined. RESULTS: Jack's results of the exploratory factor analyses and scale analyses were replicated essentially. After elimination of non-theory-compliant items, differentiation of the construct "motivation for change" and insertion of a second-order construct "self-management skills" a good confirmatorical model fit could be achieved. CONCLUSION: The FERUS can be used for MS patients. The consideration of optimization proposals allows higher construct validity and a more economical use of FERUS. PMID- 24217883 TI - [Measurement of functional independence: concordance of the assessments SINGER and FIM and consequences for the user]. AB - OBJECTIVE: The aim of this study was to evaluate the concordance between the assessments SINGER and FIM, both measurements for detecting functional disabilities in activities of daily living (ADL). METHODS: 301 rehabilitants were assessed with FIM and SINGER in the beginning and at the end of an inpatient rehabilitation program. Correla-tion coefficient, regression analysis, and Kappa statistics were applied to examine the relationship and the concordance between the 2 ADL scales. RESULTS: The assessments were highly correlated (rPearson=0.94). The regression analysis lead to the formula SINGERpred=- 0.004FIM2+1.363FIM - 15.871 with a model fit of R2=0.896. After fixing the limits for a classification due to the functional status, Inter-Rater Reliability (Kappa) was kappa=0.69. CONCLUSION: Both measurements can be used for quality assurance, therapy monitoring, and to classify patients considering their functional disability. Criteria are presented to decide which assessment should be selected. PMID- 24217885 TI - [Work place health promotion programmes of the statutory German Pension Insurance]. AB - BACKGROUND: In 2009, the amendment of S 31 Abs. 1 Nr. 2 SGB VI gave the German Pension Insurance the opportunity to provide outpatient medical treatments for insured people who have an occupation with particularly high risk of health. Ever since, the German Pension Insurance has developed various work place prevention programmes, which have been implemented as pilot projects. This article aims at systematically recording and comparatively analyzing these programmes in a synopsis which meets the current state of knowledge. METHODS: We developed an 8 page questionnaire focusing on work place prevention programmes by the German Pension Insurance. This questionnaire was sent to people in charge of all programmes known to us. RESULTS: All programmes have been drafted -across indications. They are aiming at insured people who already suffer from first health disorders but who are not in imminent need of rehabilitation. However, the concrete target groups at which the specific programmes are aimed differ (shift workers, nurses, elderly employees). Another difference between the various programmes is the setting (in- or outpatients) as well as the duration. CONCLUSION: All programmes are using existing structures offered by the German Pension Insurance. They provide measures in pension insurance owned rehabilitation centers. It would be desirable to link these performances with internal work place health promotion and offers of other social insurances. PMID- 24217884 TI - [Predictors of success of long-term treatment in alcohol dependency]. AB - OBJECTIVE: There is a lack of positive predictors for long-term treatment of subjects with alcohol addiction. We analyzed the relation between motivation and other external variables of access to treatment as well as treatment outcome. METHOD: 434 persons with alcohol addiction, treated in 2004 in the Diakonie Krankenhaus Harz (DHK), Elbingerode, as part of a long-term therapy, were followed-up one year after treatment. Access variables were defined and examined in relation to outcome variables with multiple linear and logistic regressions. RESULT: Ways of accessing treatment had no effect on later treatment outcome, while motiva-tion at the start of therapy was relevant: Patients with ambivalent motivation had the most negative outcome. CONCLUSION: Therapy motivation was the main predictor for the outcome of a long-term anti-addiction treatment. To improve the quality of the treatment system, interventions to strengthen motivation should be promoted. PMID- 24217886 TI - [The UN-Convention on the Rights of People with Disabilities and the transition from school to vocational training and career in Germany: public data sources under close scrutiny]. AB - This paper analyzes public data sources and their requirements for the transition from school to vocational training and career of people with disabilities in the context of Article 31 of the UN-Convention on Rights of People with Disabilities. Different focuses of the public data sources within the involved systems and challenges in data analysis will be presented. These manifest themselves as cross system interface problems when it comes to the identification and whereabouts of young people with disabilities at the transition from school to vocational training and employment. With these challenges public data sources on the transition from school to vocational training and employment are especially under scrutiny when it comes to developing and implementing policies in respect to the Convention on Rights for People with disabilities and the provision of adequate planning data. PMID- 24217887 TI - [Method of the assessment of patients outcome in cardiac rehabilitation by means of quality indicators--a description of the method]. AB - INTRODUCTION: Cardiac rehabilitation is designed for patients suffering from cardiovascular diseases or functional disabilities. The aim of a cardiac rehabilitation is to improve overall physical health, psychological well-being, physical function, the ability to participate in social life and help patients to change their habits. Regarding the heterogeneity of these aims measuring of the effect of cardiac rehabilitation is still a challenge. This study recommends a concept to assess the effects of cardiac rehabilitation regarding the individual change of relevant quality indicators. METHODS: With "EVA-Reha; cardiac rehabilitation" the Medical Advisory Service of Statutory Health Insurance Funds in Rhineland-Palatinate, Alzey (MDK Rheinland-Pfalz) developed a software to collect data set including sociodemographic and diagnostic data and also the results of specific assessments. The project was funded by the Techniker Krankenkasse, Hamburg, and supported by participating rehabilitation centers. From 01. July 2010 to 30. June 2011 1309 patients (age 71.5 years, 76.1% men) from 13 rehabilitation centers were consecutively enrolled. 13 quality indicators in 3 scales were developed for evaluation of cardiac rehabilitation: 1) cardiovascular risk factors (blood pressure, LDL cholesterol, triglycerides), 2) exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure [NYHA classification], and angina pectoris [CCS classification]) and 3) subjective health (IRES-24: pain, somatic health, psychological wellbeing and depression as well as anxiety on the HADS). The study was prospective; data of patients were assessed at entry and discharge of rehabilitation. To measure the success of rehabilitation each parameter was graded in severity classes at entry and discharge. For each of the 13 quality indicators changes of severity class were rated in a rating matrix. For indicators without a requirement for medical care neither at entry nor at discharge no rating was performed. RESULTS: The grading into severity classes as well as the minimal important differences were given for the 13 quality indicators. The result of rehabilitation can be demonstrated in suitable form by means of rating of the 13 quality indicators according to a clinical population. The rating model differs well between clinically changed and unchanged patients for the quality indicators. CONCLUSION: The result of cardiac rehabilitation can be assessed with 13 quality indicators measured at entry and dis-charge of the rehabilitation program. If a change into a more -favorable category at the end of rehabilitation could be achieved it was counted as a success. The 13 quality indicators can be used to assess the individual result as well as the result of a population--e. g. all patients of a clinic in a specific time period. In addition, the assessment and rating of relevant quality indicators can be used for comparisons of rehabilitation centers. PMID- 24217888 TI - [External quality assurance in inpatient medical rehabilitation and prevention centers for mothers, fathers and children: development of instruments for assessing structural quality]. AB - AIM OF THE STUDY: As required by German law, inpatient institutions offering prevention and rehabilitation measures for mothers, fathers and children are obliged to implement external quality assurance measures. In 2 pilot projects funded by the German federal association of health insurance funds, external quality assurance procedures for in-hospital prevention and rehabilitation of mothers and fathers were analyzed with the aim of developing a set of instruments for the description of structural characteristics in this area of health care and to evaluate its appropriateness. Concerning structure-related quality, the project included a) designing and evaluating a questionnaire, b) the definition of assessment criteria for subsequent comparative data analyses, and c) the description and documentation of the current state in the field of rehabilitation and prevention for mothers, fathers and children. METHOD: To document structural quality comprehensively, a modular questionnaire was developed and tested in a survey of 115 inpatient prevention and rehabilitation institutions for mothers, fathers and children. Involving an expert panel, preliminary basic and selection criteria were defined in order to assure a conducive assessment with regard to structural attributes. RESULTS: The majority of institutions had provider agreements for both prevention and rehabilitation. Measures for mothers/fathers with children were predominant; only 7 institutions exclusively treated mothers and fathers. Institution sizes varied strongly. Major indications included psychosomatics, dermatology, and pneumology. Overall, structural conditions of the institutions showed a high standard. Potential for development was found with regard to some aspects of the conceptual framework of institutional practice and the implementation of the International Classification of Functioning, Disability and Health (ICF) in diagnostics. In this article, the degrees of fulfillment with relation to the structural dimensions are presented, referring to the analysis of the preliminary basic criteria. CONCLUSIONS: The developed modular questionnaire tapping structural features of inpatient mother/father-child institutions has proven to be a useful instrument to describe the structural quality in future routine practice of quality assurance. In addition, the data can be used for the definition of the final set of criteria. PMID- 24217889 TI - [Confirmatory analysis of the dimensional structure of the ODI, the SF-12 and the HADS-D scales in a sample of rehabilitation patients with musculoskeletal diseases]. AB - This study aimed at confirmatory testing the factorial structure of the established assessment instruments ODI, SF-12 and HADS-D by means of structural equation modeling in a sample of n=184 rehabilitation patients with musculo skeletal diseases. According to local and global fit indices for each instrument an acceptable to good fit to the underlying theoretical model could be verified. For the ODI as well as for the HADS-D only single weak item-construct associations indicated shortcomings in the assumed model structure. For the SF-12 the constructs "physical health" and "mental health" could be validated after defining the additional first order factors "role - physical", "role - emotional" and "well-being", respectively. In general, the study findings proved the factorial validity of the instruments. Additionally, specific measurement properties on item and structural level could be identified which might enhance the understanding of construct definitions in rehabilitation patients with musculoskeletal diseases. PMID- 24217890 TI - Promoting a new brain tumor mutation: TERT promoter mutations in CNS tumors. PMID- 24217891 TI - Lymphomatoid papulosis type D or an aggressive epidermotropic CD8(+) cytotoxic T cell lymphoma? PMID- 24217892 TI - Procedural memory effects in categorization: evidence for multiple systems or task complexity? AB - According to an influential multiple-systems model of category learning, an implicit procedural system governs the learning of information-integration category structures, whereas a rule-based system governs the learning of explicit rule-based categories. Support for this idea has come in part from demonstrations that motor interference, in the form of inconsistent mapping between response location and category labels, results in observed deficits, but only for learning information-integration category structures. In this article, we argue that this response location manipulation results in a potentially more cognitively complex task in which the feedback is difficult to interpret. In one experiment, we attempted to attenuate the cognitive complexity by providing more information in the feedback, and demonstrated that this eliminates the observed performance deficit for information-integration category structures. In a second experiment, we demonstrated similar interference of the inconsistent mapping manipulation in a rule-based category structure. We claim that task complexity, and not separate systems, might be the source of the original dissociation between performance on rule-based and information-integration tasks. PMID- 24217893 TI - Deciding with the eye: how the visually manipulated accessibility of information in memory influences decision behavior. AB - Decision situations are typically characterized by uncertainty: Individuals do not know the values of different options on a criterion dimension. For example, consumers do not know which is the healthiest of several products. To make a decision, individuals can use information about cues that are probabilistically related to the criterion dimension, such as sugar content or the concentration of natural vitamins. In two experiments, we investigated how the accessibility of cue information in memory affects which decision strategy individuals rely on. The accessibility of cue information was manipulated by means of a newly developed paradigm, the spatial-memory-cueing paradigm, which is based on a combination of the looking-at-nothing phenomenon and the spatial-cueing paradigm. The results indicated that people use different decision strategies, depending on the validity of easily accessible information. If the easily accessible information is valid, people stop information search and decide according to a simple take-the-best heuristic. If, however, information that comes to mind easily has a low predictive validity, people are more likely to integrate all available cue information in a compensatory manner. PMID- 24217894 TI - Distinct processes shape flashbulb and event memories. AB - In the present study, we examined the relation between memory for a consequential and emotional event and memory for the circumstances in which people learned about that event, known as flashbulb memory. We hypothesized that these two types of memory have different determinants and that event memory is not necessarily a direct causal determinant of flashbulb memory. Italian citizens (N = 352) described their memories of Italy's victory in the 2006 Football World Cup Championship after a delay of 18 months. Structural equation modeling showed that flashbulb memory and event memory could be clearly differentiated and were determined by two separate pathways. In the first pathway, importance predicted emotional intensity, which, in turn, predicted the frequency of overt and covert rehearsal. Rehearsal was the only direct determinant of vivid and detailed flashbulb memories. In the second pathway, importance predicted rehearsal by media exposure, which enhanced the accuracy and certainty of event memory. Event memory was also enhanced by prior knowledge. These results have important implications for the debate concerning whether the formation of flashbulb memory and event memory involve different processes and for understanding how flashbulb memory can be simultaneously so vivid and so error-prone. PMID- 24217895 TI - "Saving" Bonnie. PMID- 24217896 TI - Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes : exploring the molecular mechanism. AB - Deltamethrin (DLM) is a well-known pyrethroid insecticide; however, the immunotoxic effects of DLM on the mammalian system and its mechanism is still unclear. This study has been designed to first observe the binding affinity of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has a strong binding affinity towards the CD4 and CD8 receptors. DLM induces apoptosis in murine thymocytes in a concentration dependent manner. The ear?ly markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation are evident as early as 1 h by 25 and 50 MUM DLM. Glutathione (GSH) depletion has also been observed at 1 h by 50 MUM DLM concentration. In cell-cycle studies using flow cytometry, the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. The Annexin V binding assay measures the effect of DLM on apoptotic and necrotic cells. The apoptotic cells raised from 18.6% to 35.21% (10-50 MUM DLM) at 18 h. N-acetyl cysteine (NAC) effectively reduced the percentage of apoptotic cells which is increased by DLM. In contrast, buthionine sulfoximine (BSO) caused an elevation in the percentage of apoptotic cells. These results demonstrate that caspase activation, ROS activation and GSH act as critical mediators in a DLM induced apoptogenic signalling pathway in murine thymocytes. In the presence of caspase inhibitor, the percentage of apoptotic cells is partially decreased. Thus, there may be the possibility of some other caspase-independent pathways in DLM-induced apoptosis. PMID- 24217897 TI - Lindane degradation by Candida VITJzN04, a newly isolated yeast strain from contaminated soil: kinetic study, enzyme analysis and biodegradation pathway. AB - A new yeast strain was isolated from sugarcane cultivation field which was able to utilize lindane as sole carbon source for growth in mineral medium. The yeast was identified and named as Candida sp. VITJzN04 based on a polyphasic approach using morphological, biochemical and 18S rDNA, D1/D2 and ITS sequence analysis. The isolated yeast strain efficiently degraded 600 mg L-1 of lindane within 6 days in mineral medium under the optimal conditions (pH 7; temperature 30 degrees C and inoculum dosage 0.06 g L-1) with the least half-life of 1.17 days and degradation constant of 0.588 per day. Lindane degradation was tested with various kinetic models and results revealed that the reaction could be described best by first-order and pseudo first-order models. In addition, involvement of the enzymes viz. dechlorinase, dehalogenase, dichlorohydroquinone reductive dechlorinase, lignin peroxidase and manganese peroxidase was noted during lindane degradation. Addition of H2O2 in the mineral medium showed 32 % enhancement of lindane degradation within 3 days. Based on the metabolites identified by GC-MS and FTIR analysis, sequential process of lindane degradation by Candida VITJzN04 was proposed. To the best of our knowledge, this is the first report of isolation and characterization of lindane-degrading Candida sp. and elucidation of enzyme systems during the degradation process. PMID- 24217898 TI - Obestatin: a new metabolic player in the pancreas and white adipose tissue. AB - Obestatin is a 23 amino acid amidated peptide, member of the preproghrelin gene derived peptides. Initially, obestatin was reported to exert opposite effects to those of ghrelin on food intake and body weight gain, through interaction with GPR39; however, these findings are still strongly debated and obestatin biological role remains largely unknown. Interestingly, binding of obestatin to the glucagon-like peptide 1 receptor has been recently suggested. Despite being a controversial peptide, recent findings have clearly indicated that obestatin is indeed a multifunctional peptide, exerting a variety of effects, such as stimulation of cell proliferation, survival and differentiation, influence on glucose and lipid metabolism, as well as anti-inflammatory and cardioprotective actions. Its positive effects on glucose and lipid metabolism candidate this peptide as a potential therapeutic tool in pathological conditions such as insulin resistance and diabetes. PMID- 24217899 TI - Demand curves for hypothetical cocaine in cocaine-dependent individuals. AB - RATIONALE: Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. OBJECTIVES: This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. METHODS: Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. RESULTS: Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. CONCLUSIONS: Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID- 24217901 TI - Coexistence of malignant struma ovarii and cervical papillary thyroid carcinoma. AB - CONTEXT: Struma ovarii is an uncommon monodermal teratoma in which thyroid tissue is the predominant element. Malignant transformation of struma ovarii is an even rarer occurrence. CASE PRESENTATION: We describe a 42-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a symptomatic left pelvic mass. Histology revealed malignant struma ovarii with classical papillary thyroid carcinoma expression. Ultrasonography of the cervical neck showed thyroid micronodules and a dominant 1-cm nodule in the left thyroid lobe. As the ovarian tumor was large, the patient underwent a total thyroidectomy with the intention of administering 131I therapy in an adjuvant setting. Histology of the cervical thyroid gland revealed bilateral multifocal papillary thyroid carcinoma with extrathyroidal extension and perithyroidal lymph node metastasis. METHODS: Morphological (microscopy), immunohistochemical (Hector Battifora mesothelial cell 1, cytokeratin-19, galectin-3), and molecular (BRAF V600E, RAS, RET-PTC) characteristics and clonality analysis of the cervical thyroid and ovarian tumors were explored to distinguish them as separate malignancies. RESULTS: The thyroid-type tumors from the cervical gland and ovary were discordant in terms of tissue histology and level of cytokeratin-19 expression. The clinical features and tumor profile results supported the independent existence of these two embryologically related, although topographically distinct, malignancies. CONCLUSION: Our findings provided support for synchronous, albeit distinct, primary tumors in the ovary and cervical thyroid. "Field cancerization" and early genomic instability may explain multifocality in all thyroid-type tissue. In this regard, patients with malignant struma ovarii should undergo imaging of their thyroid gland for coexisting disease and thyroidectomy recommended for suspected malignancy or in preparation for radioiodine therapy. PMID- 24217900 TI - Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain. AB - RATIONALE: Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates. OBJECTIVE: The aims of this study were to develop carrageenan-induced hyperalgesia in rhesus monkeys and determine the efficacy and potency of agonists selective for the four opioid receptor subtypes in this model versus acute pain, as compared to non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: Tail injection of carrageenan produced long-lasting thermal hyperalgesia in monkeys. Systemically administered agonists selective for opioid receptor subtypes, i.e., fentanyl (mu/MOP), U-50488H (kappa/KOP), SNC80 (delta/DOP) and Ro 64-6198 (nociceptin/orphanin FQ/NOP) dose-dependently attenuated carrageenan-induced thermal hyperalgesia with different potencies. In absence of carrageenan, these agonists, except SNC80, blocked acute thermal nociception. Opioid-related ligands, especially Ro 64-6198, were much more potent for their antihyperalgesic than antinociceptive effects. Both effects were mediated by the corresponding receptor mechanisms. Only fentanyl produced scratching at antihyperalgesic and antinociceptive doses consistent with its pruritic effects in humans, illustrating a translational profile of MOP agonists in nonhuman primates. Similar to SNC80, systemically administered NSAIDs ketorolac and naproxen dose dependently attenuated carrageenan-induced hyperalgesia but not acute nociception. CONCLUSION: Using two different pain modalities in nonhuman primates, effectiveness of clinically available analgesics like fentanyl, ketorolac and naproxen was distinguished and their efficacies and potencies were compared with the selective KOP, DOP, and NOP agonists. The opioid-related ligands displayed differential pharmacological properties in regulating hyperalgesia and acute nociception in the same subjects. Such preclinical primate models can be used to investigate novel analgesic agents. PMID- 24217902 TI - The adverse health consequences of the use of multiple performance-enhancing substances--a deadly cocktail. AB - CONTEXT: The harmful consequences of abuse of performance-enhancing substances (PESs), stimulants, and masking agents among athletes, recreational weight lifters, and physical trainers are common. However, the adverse health outcomes with severe unexpected and dramatic consequences are unrecognized or under reported at the expense of short-term glory or body-image effects, especially in elite sports. OBJECTIVE: We report the case of a recreational weight lifter/physical trainer to help summarize the adverse health consequences and outcomes of polypharmacy among athletes and growing subsets in our population engaged in physical/fitness training. We show that in addition to the risk inherent to "stacking" of PESs, the users are predisposed to harmful consequences, including risk of exposure to toxic contaminants. DESIGN AND SETTING: A previously healthy man with chronic use of multiple PESs, stimulants, and masking agents presented to a tertiary-care hospital with jaundice and mild hepatitis with rapid progression into liver and multisystem organ failure. This is followed by a brief overview of the specific toxicity (arsenic) and PESs that contributed to the poor outcome in this case. CONCLUSION: Surreptitiously or self administered cocktails of potential PESs including anabolic agents, emerging classes of GH-releasing peptides, androgen precursors, stimulants, and masking agents could lead to adverse consequences including early mortality, multisystem pathology, unmask/accelerate malignancy, and expose or predispose users to extreme danger from contaminants. This cautionary case reinforces the need to increase awareness and highlights the challenges that testing agencies, regulators, and clinicians face in the fast-developing licit/illicit trade of these products. PMID- 24217903 TI - Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH--an update. AB - CONTEXT: GH deficiency (GHD) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality. It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality. EVIDENCE ACQUISITION: The major source of data acquisition included PubMed research strategies. Original articles, systematic reviews and meta analyses, and included relevant citations were screened. EVIDENCE SYNTHESIS: In untreated GHD, cardiovascular risk is increased due to abnormal lipid profile (increased total and low-density lipoprotein cholesterol, increased triglycerides, and reduced high-density lipoprotein cholesterol) and impaired glucose metabolism. Emerging cardiovascular risk factors/markers such as proinflammatory cytokines, C-reactive protein, and adipokines are also increased in GHD patients. Increased cardiovascular morbidity and mortality have also been reported in GHD. GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers. However, evidence on the effects of GH replacement on cardiovascular events and mortality is limited. CONCLUSION: The GHD population may be considered at high cardiovascular risk, and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection. However, there is too limited evidence (rarely coming from randomized and controlled studies) to recommend GH treatment based on the cardiovascular status of the patients. PMID- 24217904 TI - Determination of reference intervals for serum total calcium in the vitamin D replete pediatric population. AB - CONTEXT: Widespread vitamin D insufficiency raises concerns regarding the reliability of reference intervals for serum calcium. OBJECTIVE: We sought to determine the reference intervals for serum total calcium in pediatric subjects without vitamin D [25-hydroxyvitamin D [25(OH)D]] deficiency [20 ng/mL (50 nmol/L)]. DESIGN AND PARTICIPANTS: This was a retrospective study of laboratory data obtained from all patients at The Children's Hospital of Philadelphia from July 1, 2011, through June 30, 2012. Patients in the renal unit, the endocrine unit, or a critical care unit were excluded. Total serum calcium was determined using a colorimetric assay and serum 25(OH)D was determined by liquid chromatography tandem mass spectrometry. We ascertained 4629 subjects who had a serum 25(OH)D between 20 and 80 ng/mL (50-200 nmol/L) and a serum calcium level determined within 30 days of the 25(OH)D measurement. For comparison, we used data from an unselected cohort of patients (n = 106 220). RESULTS: Parametric analyses generated age-specific reference intervals for serum total calcium for each of several age groups (0-90 d old, 91-180 d old, 181-365 d old, 1-3 y old, 4 11 y old, and 12-19 y old). A two-way ANOVA with Tukey's correction showed significant differences between the lower limits of normal (P < .001) and the normal range (P < .001) but not for the upper limit of normal for these subjects compared with unselected subjects. Student's t tests revealed significant differences at all ages between calcium concentrations in those with 25(OH)D values between 20 and 30 ng/mL and those with 25(OH)D values between 30 and 80 ng/mL. CONCLUSIONS: These reference intervals refine previous normal ranges that likely included subjects with vitamin D deficiency. PMID- 24217905 TI - Expression and subcellular localization of estrogen receptors alpha and beta in human fetal brown adipose tissue. AB - CONTEXT: Brown adipose tissue (BAT) has the unique ability of generating heat due to the expression of mitochondrial uncoupling protein 1 (UCP1). A recent discovery regarding functional BAT in adult humans has increased interest in the molecular pathways of BAT development and functionality. An important role for estrogen in white adipose tissue was shown, but the possible role of estrogen in human fetal BAT (fBAT) is unclear. OBJECTIVE: The objective of this study was to determine whether human fBAT expresses estrogen receptor alpha (ERalpha) and ERbeta. In addition, we examined their localization as well as their correlation with crucial proteins involved in BAT differentiation, proliferation, mitochondriogenesis and thermogenesis including peroxisome proliferator-activated receptor gamma (PPARgamma), proliferating cell nuclear antigen (PCNA), PPARgamma coactivator-1alpha (PGC-1alpha), and UCP1. DESIGN: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20, and 23 weeks gestation. ERalpha and ERbeta expression was assessed using Western blotting, immunohistochemistry, and immunocytochemistry. Possible correlations with PPARgamma, PCNA, PGC-1alpha, and UCP1 were examined by double immunofluorescence. RESULTS: Both ERalpha and ERbeta were expressed in human fBAT, with ERalpha being dominant. Unlike ERbeta, which was present only in mature brown adipocytes, we detected ERalpha in mature adipocytes, preadipocytes, mesenchymal and endothelial cells. In addition, double immunofluorescence supported the notion that differentiation in fBAT probably involves ERalpha. Immunocytochemical analysis revealed mitochondrial localization of both receptors. CONCLUSION: The expression of both ERalpha and ERbeta in human fBAT suggests a role for estrogen in its development, primarily via ERalpha. In addition, our results indicate that fBAT mitochondria could be targeted by estrogens and pointed out the possible role of both ERs in mitochondriogenesis. PMID- 24217906 TI - Five-year follow-up for women with subclinical hypothyroidism in pregnancy. AB - CONTEXT: Increasing numbers of women are being treated with l-thyroxine in pregnancy for mild thyroid dysfunction because of its association with impaired neuropsychological development in their offspring and other adverse obstetric outcomes. However, there are limited data to indicate whether treatment should be continued outside of pregnancy. OBJECTIVES: We aimed to determine whether subclinical hypothyroidism and maternal hypothyroxinemia resolve postdelivery. DESIGN, SETTING, AND PARTICIPANTS: A total of 523 pregnant healthy women with no known thyroid disorders were recruited during routine antenatal care and provided blood samples at 28 weeks of pregnancy and at a mean of 4.9 years postpregnancy. MAIN OUTCOME MEASURES: TSH, free T4, free T3, and thyroid peroxidase antibody levels were measured in serum taken in pregnancy and at follow-up. RESULTS: Subclinical hypothyroidism in pregnancy (TSH >3 mIU/L) was present in 65 of 523 (12.4%) women. Of these, 49 (75.4%) women had normal thyroid function postpregnancy; 16 of 65 (24.6%) had persistent high TSH (TSH >4.5 mIU/L postpregnancy) with 3 women receiving l-thyroxine treatment. A total of 44 of 523 (8.4%) women had isolated maternal hypothyroxinemia in pregnancy (free T4 <10th centile and TSH <=3 mIU/L). Only 2 of 44 (4.5%) had TSH >4.5 mIU/L outside pregnancy. Of the women with subclinical hypothyroidism in pregnancy with antibody measurements available, those with thyroid peroxidase antibodies in pregnancy were more likely to have persistently elevated TSH or be receiving l thyroxine replacement after pregnancy (6 of 7 [86%] vs 10 of 57 [18%], P < .001). CONCLUSIONS: The majority of cases of subclinical hypothyroidism in pregnancy are transient, so treatment with l-thyroxine in these patients should be reviewed because it may not be warranted after pregnancy. PMID- 24217907 TI - Oncogenic osteomalacia caused by renal cell carcinoma. PMID- 24217908 TI - Postnatal ovarian activation has effects in estrogen target tissues in infant girls. AB - CONTEXT: Shortly after birth, pituitary gonadotropin secretion transiently activates in both sexes, and this surge is more robust in preterm (PT) than in full-term (FT) infants. In boys, the gonadotropin surge is associated with testicular activity and is considered an important part of normal reproductive development. In contrast, gonadal activation and its consequences in infant girls are poorly understood. OBJECTIVE: Our objective was to evaluate the association of postnatal ovarian activity with simultaneous changes in estrogen target tissues in FT and PT girls. PATIENTS AND METHODS: We measured urinary estradiol (E2) levels in 29 FT and 34 PT girls using a mass spectrometric method from 1 week (D7) to 6 months of age (M1-M6). To assess the contribution of ovarian E2 on urinary E2 levels, the levels in girls were compared with the levels of boys of similar cohorts (29 FT and 33 PT boys). E2 levels were compared with simultaneous changes in estrogenic target tissues including mammary glands in both sexes and uterus and vulvar epithelium in girls. RESULTS: Median urinary E2 levels increased after D7 in girls, but not in boys. Mammary gland diameter was larger in girls than in boys from M4 in FT (P < .001) and M2 in PT infants (P < .0001). In PT girls, E2 levels increased at term and were then higher than those in FT girls (P < .0001). Urinary E2 levels in PT girls were positively associated with mammary gland and uterine growth. CONCLUSIONS: These findings indicate that gonadal steroidogenesis activates during the postnatal gonadotropin surge in girls. In addition, the resulting elevated E2 levels affect target tissues, suggesting that postnatal pituitary-ovarian activation plays a role in normal female reproductive development. PMID- 24217909 TI - Current status and new features of the Consensus Coding Sequence database. AB - The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets. PMID- 24217910 TI - Characterization of the imprinting signature of mouse embryo fibroblasts by RNA deep sequencing. AB - Mouse embryo fibroblasts (MEFs) are convenient sources for biochemical studies when cell number in mouse embryos is limiting. To derive the imprinting signature of MEFs and potentially detect novel imprinted genes we performed strand- and allele-specific RNA deep sequencing. We used sequenom allelotyping in embryo and adult organs to verify parental allele-specific expression. Thirty-two known ubiquitously imprinted genes displayed correct parental allele-specific transcripts in MEFs. Our analysis did not reveal any novel imprinted genes, but detected extended parental allele-specific transcripts in several known imprinted domains: maternal allele-specific transcripts downstream of Grb10 and downstream of Meg3, Rtl1as and Rian in the Dlk1-Dio3 cluster, an imprinted domain implicated in development and pluripotency. We detected paternal allele-specific transcripts downstream of Nespas, Peg3, Peg12 and Snurf/Snrpn. These imprinted transcript extensions were not unique to MEFs, but were also present in other somatic cells. The 5' end points of the imprinted transcript extensions did not carry opposing chromatin marks or parental allele-specific DNA methylation, suggesting that their parental allele-specific transcription is under the control of the extended imprinted genes. Based on the imprinting signature of MEFs, these cells provide valid models for understanding the biochemical aspects of genomic imprinting. PMID- 24217911 TI - AgeFactDB--the JenAge Ageing Factor Database--towards data integration in ageing research. AB - AgeFactDB (http://agefactdb.jenage.de) is a database aimed at the collection and integration of ageing phenotype data including lifespan information. Ageing factors are considered to be genes, chemical compounds or other factors such as dietary restriction, whose action results in a changed lifespan or another ageing phenotype. Any information related to the effects of ageing factors is called an observation and is presented on observation pages. To provide concise access to the complete information for a particular ageing factor, corresponding observations are also summarized on ageing factor pages. In a first step, ageing related data were primarily taken from existing databases such as the Ageing Gene Database--GenAge, the Lifespan Observations Database and the Dietary Restriction Gene Database--GenDR. In addition, we have started to include new ageing-related information. Based on homology data taken from the HomoloGene Database, AgeFactDB also provides observation and ageing factor pages of genes that are homologous to known ageing-related genes. These homologues are considered as candidate or putative ageing-related genes. AgeFactDB offers a variety of search and browse options, and also allows the download of ageing factor or observation lists in TSV, CSV and XML formats. PMID- 24217912 TI - The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. AB - The Human Phenotype Ontology (HPO) project, available at http://www.human phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web based tools. All data and documentation on the HPO project can be found online. PMID- 24217913 TI - The Drosophila RNA-binding protein HOW controls the stability of dgrasp mRNA in the follicular epithelium. AB - Post-transcriptional regulation of RNA stability and localization underlies a wide array of developmental processes, such as axon guidance and epithelial morphogenesis. In Drosophila, ectopic expression of the classically Golgi peripheral protein dGRASP at the plasma membrane is achieved through its mRNA targeting at key developmental time-points, in a process critical to follicular epithelium integrity. However, the trans-acting factors that tightly regulate the spatio-temporal dynamics of dgrasp are unknown. Using an in silico approach, we identified two putative HOW Response Elements (HRE1 and HRE2) within the dgrasp open reading frame for binding to Held Out Wings (HOW), a member of the Signal Transduction and Activation of RNA family of RNA-binding proteins. Using RNA immunoprecipitations, we confirmed this by showing that the short cytoplasmic isoform of HOW binds directly to dgrasp HRE1. Furthermore, HOW loss of function in vivo leads to a significant decrease in dgrasp mRNA levels. We demonstrate that HRE1 protects dgrasp mRNA from cytoplasmic degradation, but does not mediate its targeting. We propose that this binding event promotes the formation of ribonucleoprotein particles that ensure dgrasp stability during transport to the basal plasma membrane, thus enabling the local translation of dgrasp for its roles at non-Golgi locations. PMID- 24217914 TI - GenBank. AB - GenBank is a comprehensive database that contains publicly available nucleotide sequences for over 280,000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun and environmental sampling projects. Most submissions are made using the web based BankIt or standalone Sequin programs, and GenBank staff assign accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI home page: www.ncbi.nlm.nih.gov. PMID- 24217915 TI - WormQTLHD--a web database for linking human disease to natural variation data in C. elegans. AB - Interactions between proteins are highly conserved across species. As a result, the molecular basis of multiple diseases affecting humans can be studied in model organisms that offer many alternative experimental opportunities. One such organism-Caenorhabditis elegans-has been used to produce much molecular quantitative genetics and systems biology data over the past decade. We present WormQTL(HD) (Human Disease), a database that quantitatively and systematically links expression Quantitative Trait Loci (eQTL) findings in C. elegans to gene disease associations in man. WormQTL(HD), available online at http://www.wormqtl hd.org, is a user-friendly set of tools to reveal functionally coherent, evolutionary conserved gene networks. These can be used to predict novel gene-to gene associations and the functions of genes underlying the disease of interest. We created a new database that links C. elegans eQTL data sets to human diseases (34 337 gene-disease associations from OMIM, DGA, GWAS Central and NHGRI GWAS Catalogue) based on overlapping sets of orthologous genes associated to phenotypes in these two species. We utilized QTL results, high-throughput molecular phenotypes, classical phenotypes and genotype data covering different developmental stages and environments from WormQTL database. All software is available as open source, built on MOLGENIS and xQTL workbench. PMID- 24217916 TI - NPInter v2.0: an updated database of ncRNA interactions. AB - NPInter (http://www.bioinfo.org/NPInter) is a database that integrates experimentally verified functional interactions between noncoding RNAs (excluding tRNAs and rRNAs) and other biomolecules (proteins, RNAs and genomic DNAs). Extensive studies on ncRNA interactions have shown that ncRNAs could act as part of enzymatic or structural complexes, gene regulators or other functional elements. With the development of high-throughput biotechnology, such as cross linking immunoprecipitation and high-throughput sequencing (CLIP-seq), the number of known ncRNA interactions, especially those formed by protein binding, has grown rapidly in recent years. In this work, we updated NPInter to version 2.0 by collecting ncRNA interactions from recent literature and related databases, expanding the number of entries to 201 107 covering 18 species. In addition, NPInter v2.0 incorporated a service for the BLAST alignment search as well as visualization of interactions. PMID- 24217917 TI - Prospective identification of parasitic sequences in phage display screens. AB - Phage display empowered the development of proteins with new function and ligands for clinically relevant targets. In this report, we use next-generation sequencing to analyze phage-displayed libraries and uncover a strong bias induced by amplification preferences of phage in bacteria. This bias favors fast-growing sequences that collectively constitute <0.01% of the available diversity. Specifically, a library of 10(9) random 7-mer peptides (Ph.D.-7) includes a few thousand sequences that grow quickly (the 'parasites'), which are the sequences that are typically identified in phage display screens published to date. A similar collapse was observed in other libraries. Using Illumina and Ion Torrent sequencing and multiple biological replicates of amplification of Ph.D.-7 library, we identified a focused population of 770 'parasites'. In all, 197 sequences from this population have been identified in literature reports that used Ph.D.-7 library. Many of these enriched sequences have confirmed function (e.g. target binding capacity). The bias in the literature, thus, can be viewed as a selection with two different selection pressures: (i) target-binding selection, and (ii) amplification-induced selection. Enrichment of parasitic sequences could be minimized if amplification bias is removed. Here, we demonstrate that emulsion amplification in libraries of ~ 10(6) diverse clones prevents the biased selection of parasitic clones. PMID- 24217918 TI - Gramene 2013: comparative plant genomics resources. AB - Gramene (http://www.gramene.org) is a curated online resource for comparative functional genomics in crops and model plant species, currently hosting 27 fully and 10 partially sequenced reference genomes in its build number 38. Its strength derives from the application of a phylogenetic framework for genome comparison and the use of ontologies to integrate structural and functional annotation data. Whole-genome alignments complemented by phylogenetic gene family trees help infer syntenic and orthologous relationships. Genetic variation data, sequences and genome mappings available for 10 species, including Arabidopsis, rice and maize, help infer putative variant effects on genes and transcripts. The pathways section also hosts 10 species-specific metabolic pathways databases developed in house or by our collaborators using Pathway Tools software, which facilitates searches for pathway, reaction and metabolite annotations, and allows analyses of user-defined expression datasets. Recently, we released a Plant Reactome portal featuring 133 curated rice pathways. This portal will be expanded for Arabidopsis, maize and other plant species. We continue to provide genetic and QTL maps and marker datasets developed by crop researchers. The project provides a unique community platform to support scientific research in plant genomics including studies in evolution, genetics, plant breeding, molecular biology, biochemistry and systems biology. PMID- 24217919 TI - Discover context-specific combinatorial transcription factor interactions by integrating diverse ChIP-Seq data sets. AB - Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. Current knowledge about combinatorial regulation is rather limited due to the lack of suitable experimental technologies and bioinformatics tools. The rapid accumulation of ChIP-Seq data has provided genome-wide occupancy maps for a large number of TFs and chromatin modification marks for identifying enhancers without knowing individual TF binding sites. Integration of the two data types has not been researched extensively, resulting in underused data and missed opportunities. We describe a novel method for discovering frequent combinatorial occupancy patterns by multiple TFs at enhancers. Our method is based on probabilistic item set mining and takes into account uncertainty in both types of ChIP-Seq data. By joint analysis of 108 TFs in four human cell types, we found that cell-type-specific interactions among TFs are abundant and that the majority of enhancers have flexible architecture. We show that several families of transposable elements disproportionally overlap with enhancers with combinatorial patterns, suggesting that these transposable element families play an important role in the evolution of combinatorial regulation. PMID- 24217921 TI - Transcription control of DAPK. AB - Imbalanced cell death is a common phenomenon in many human diseases, including cancer. DAPK's essential function is in promoting apoptosis. DAPK interacts with stress-induced receptors through its death domain to initiate an apoptosis cascade. In addition, DAPK phosphorylates multiple cytosolic substrates and can mediate transfer of signaling pathways to the effector caspases. A series of studies demonstrated that, depending on stimuli, DAPK expression is regulated on both the transcriptional and posttranscriptional levels. Silencing of DAPK due to hypermethylation of its promoter was reported in many types of cancer. STAT3 and p52-NFkB transcription factors have been shown to down-regulate DAPK expression. In contrast, p53, C/EBP-beta and Smad transcription factors bind to their specific response elements within the DAPK promoter and induce its transcription. Post-transcriptionally, DAPK undergoes alternative splicing, which results in the production of two functionally different isoforms. Moreover, miRNA 103 and miRNA 107 recently were shown to inhibit DAPK in colorectal cancer. Here we summarize our recent knowledge about transcriptional regulation of DAPK expression. PMID- 24217920 TI - Cellular senescence mediated by p16INK4A-coupled miRNA pathways. AB - p16 is a key regulator of cellular senescence, yet the drivers of this stable state of proliferative arrest are not well understood. Here, we identify 22 senescence-associated microRNAs (SA-miRNAs) in normal human mammary epithelial cells. We show that SA-miRNAs-26b, 181a, 210 and 424 function in concert to directly repress expression of Polycomb group (PcG) proteins CBX7, embryonic ectoderm development (EED), enhancer of zeste homologue 2 (EZH2) and suppressor of zeste 12 homologue (Suz12), thereby activating p16. We demonstrate the existence of a tight positive feedback loop in which SA-miRNAs activate and re enforce the expression of other SA-miRNA members. In contrast, PcG members restrain senescence by epigenetically repressing the expression of these SA miRNAs. Importantly, loss of p16 leads to repression of SA-miRNA expression, intimately coupling this effector of senescence to the SA-miRNA/PcG self regulatory loop. Taken together, our findings illuminate an important regulatory axis that underpins the transition from proliferation to cellular senescence. PMID- 24217922 TI - Therapeutic effects of suppressors of cytokine signaling in diabetic nephropathy. AB - Inflammation is an important pathophysiological mechanism in diabetic nephropathy (DN). Tubular epithelial cell-myofibroblast transdifferentiation (TEMT), which can be induced by many cytokines, is an important event in DN. Oncostatin M (OSM), an inflammatory cytokine, can induce TEMT in vitro. The suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of cytokine signaling. The purpose of this study was to investigate the role of SOCS in DN. The results demonstrated that overexpression of SOCS ameliorated proteinuria, the expression of alpha-SMA and OSM in tubular epithelial cells, and interstitial extracellular matrix accumulation in the renal tissue of CD-1 mice. In addition, our previous studies indicated that OSM induced TEMT by activating the JAK/STAT pathway, which could be inhibited by SOCS. These results indicate that overexpression of SOCS has a therapeutic effect in DN. PMID- 24217923 TI - Carbonic anhydrase IX expression is associated with favorable prognostic factors in small intestinal carcinoma. AB - Tumor hypoxia is associated with more aggressive behavior and resistance to chemotherapy and radiotherapy. Carbonic anhydrase IX (CA9) level increases under hypoxia and is related to poor prognostic factors. The aim of this study was to evaluate the expression of CA9 and to identify its prognostic significance in small intestinal carcinomas (SICs). CA9 expression was observed in 36% (63/175) of SICs. CA9 expression showed significant correlation with well- and moderately differentiated tumors compared with poorly differentiated tumors (p=0.039), tumors with no lymph node metastasis (p=0.005), and lower stage carcinomas (p=0.009). CA9 expression showed an inverse correlation with perineural invasion (p=0.021) and lymphatic invasion (p=0.022). No significant correlation was observed between CA9 expression and gross type, histological type, pathological tumor (pT) classification, vascular invasion, pancreas invasion, and retroperitoneal seeding. SICs with CA9 overexpression showed better overall survival compared with those with no or weak CA9 expression (p=0.048). In the multivariate analysis, poorly differentiated SICs (p<0.001) and SICs with lymph node metastasis (p=0.002) were independent poor prognostic factors. CA9 expression in SICs is more frequently associated with good prognostic markers and better overall survival; however, it is not an independent prognostic factor. PMID- 24217925 TI - Peer review and reproducibility. Crisis or time for course correction? PMID- 24217924 TI - Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes. AB - Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF+/-) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF+/- mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF+/- mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR. PMID- 24217927 TI - Metronidazole-induced fixed drug eruption. PMID- 24217926 TI - Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat. AB - Transient receptor potential (TRP) cation channels are emerging in vascular biology. In particular, the expression of the capsaicin receptor (TRPV1) was reported in vascular smooth muscle cells. This study characterized the arteriolar TRPV1 function and expression in the rat. TRPV1 mRNA was expressed in various vascular beds. Six commercially available antibodies were tested for TRPV1 specificity. Two of them were specific (immunostaining was abolished by blocking peptides) for neuronal TRPV1 and one recognized vascular TRPV1. TRPV1 was expressed in blood vessels in the skeletal muscle, mesenteric and skin tissues, as well as in the aorta and carotid arteries. TRPV1 expression was found to be regulated at the level of individual blood vessels, where some vessels expressed, while others did not express TRPV1 in the same tissue sections. Capsaicin (a TRPV1 agonist) evoked constrictions in skeletal muscle arteries and in the carotid artery, but had no effect on the femoral and mesenteric arteries or the aorta. In blood vessels, TRPV1 expression was detected in most of the large arteries, but there were striking differences at level of the small arteries. TRPV1 activity was suppressed in some isolated arteries. This tightly regulated expression and function suggests a physiological role for vascular TRPV1. PMID- 24217928 TI - Mediastinal emphysema: a rare respiratory complication of relapsing polychondritis. PMID- 24217929 TI - A young patient with recurrent respiratory tract infection and anasarca. AB - A young man with a history of recurrent respiratory tract infections for the past 8 years presented with generalised anasarca. He was found to have advanced renal disease (stage 4) and a profound proteinuria of 82.9 g/day. Further workup revealed the presence of advanced bronchiectatic changes in the lungs. Rectal biopsy showed the characteristic pattern of amyloid deposition. A diagnosis of systemic amyloidosis secondary to bronchiectasis was made. To the best of our knowledge no other cases of bronchiectasis-associated renal amyloid disease with such marked proteinuria have been reported in the literature. Our patient had a relatively short duration between the onset of his symptoms related to underlying bronchiectasis and his clinical presentation of renal amyloidosis. He had an aggressive course of disease and unfortunately died at a very young age. PMID- 24217930 TI - Multisystemic tuberculosis presenting with scrofula, intestinal and pulmonary involvement. PMID- 24217931 TI - Steinert's disease. PMID- 24217932 TI - Spontaneous fractures in a 30-year-old woman following a simple fall. PMID- 24217933 TI - Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients. AB - CONTEXT: Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome. OBJECTIVE: To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. DESIGN AND SETTING: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. PATIENTS: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. INTERVENTIONS: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. RESULTS: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25; P=0.04) and the number of concomitant medications, other than SSTa (B=3.9; P=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. CONCLUSIONS: UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy. PMID- 24217934 TI - The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial. AB - OBJECTIVE: Preclinical studies, observational studies, and clinical trials suggest that thiazolidinediones (TZDs) reduce bone mineral density (BMD) and increase fracture risk. Most of the evidence on the skeletal effects of TZDs is from studies of rosiglitazone. We set out to investigate the magnitude and etiology of the adverse skeletal effects of pioglitazone. DESIGN: Double-blind, randomized controlled trial. TRIAL REGISTRATION: AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY, ACTR.ORG.AU IDENTIFIER: ACTRN12607000610437, date of registration 28/11/07. METHODS: A total of 86 people with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT), median age 64 years, were randomized to receive either pioglitazone 30 mg/day or placebo for 1 year, in addition to their usual diabetes treatments. The primary outcome was change in lumbar spine BMD; secondary outcomes included changes in BMD at other sites and in biochemical markers of bone turnover. RESULTS: Change in spine BMD was not altered by treatment with pioglitazone (Ptreatment*time=0.5). After 1 year, the mean (95% CI) between-groups difference in lumbar spine BMD was -0.7% (-2.1, 0.7). Pioglitazone increased bone loss at the proximal femur (Ptreatment*time=0.03). After 12 months, the between-groups difference in total hip BMD was -1.2% (-2.1, 0.2). Pioglitazone did not alter change in BMD at other skeletal sites, nor did it affect changes in the levels of either of the biochemical markers of bone turnover, procollagen type 1 N-terminal propeptide, or beta-C-terminal telopeptide of type 1 collagen. CONCLUSIONS: Over 1 year, treatment with pioglitazone 30 mg/day did not produce consistent effects on either BMD or bone turnover in people with T2DM or IGT. The mechanism(s) by which pioglitazone increases fracture risk in T2DM is unclear. PMID- 24217935 TI - Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement. AB - BACKGROUND: Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults. OBJECTIVE: To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI. METHODS: One hundred and sixty-one GHD patients (aged 40-70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45-66 years) from the general population (NEO Study). RESULTS: MS PROPORTION IN GHD PATIENTS WAS 41.0% BEFORE THE START OF RHGH SUPPLETION, INCREASING TO 53.4% AFTER 5 YEARS (P=0.007). DESPITE CHRONIC RHGH REPLACEMENT, GHD PATIENTS HAD A 1.3-TIMES HIGHER MS PROPORTION THAN THE GENERAL POPULATION, INDEPENDENTLY OF AGE, SEX, AND BMI (95% CI 1.11.5, P=0.008). THE GHD POPULATION SHOWED A DIFFERENT METABOLIC PROFILE THAN THE GENERAL POPULATION WITH SIMILAR BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7-2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5-2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4-0.7). CONCLUSIONS: Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement. PMID- 24217936 TI - Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients. AB - OBJECTIVE: A polymorphism in the promoter region of the IGF1 gene has been linked to serum IGF1 levels, risk of diabetes, and cardiovascular diseases with conflicting results. The aim of this study was to investigate the impact of this polymorphism on the short-term (1 year, n=98) and long-term (5 years, n=50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults. DESIGN AND METHODS: Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 cytosine-adenosine-repeats), subjects were divided into homozygous (19/19), heterozygous (19/X), and noncarriers (X/X). RESULTS: Basal characteristics of patients as well as their response to rhGH in terms of decrease in body fat percentage and increase in IGF1 levels were not different in the three genotype groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and homeostasis model assessment of insulin resistance) and a significant improvement in lipid profile (i.e. reduction in total cholesterol and LDL-cholesterol) were recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous subjects, but not in noncarrier subjects. No difference in rhGH dose among groups was recorded throughout the study. CONCLUSIONS: In GHD adults, the presence of the WT allele in the IGF1 gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH. PMID- 24217937 TI - Long-term remission and recurrence rates after first and second transsphenoidal surgery for Cushing's disease: care reality in the Munich Metropolitan Region. AB - OBJECTIVE: Transsphenoidal surgery (TSS) presents the treatment of choice for Cushing's disease (CD). Remission and recurrence rates vary dependent on tumor size, extension, adenoma visibility on magnetic resonance imaging, and neurosurgical expertise. Other than published from single-surgeon neurosurgical series so far, we have aimed to describe long-term remission and recurrence rates of CD in a series incorporating different neurosurgeons, trying to reflect care reality in the Munich Metropolitan Region, which is accommodated by three tertiary university and multiple, smaller neurosurgical centers. DESIGN: We conducted a retrospective analysis of 120 patients who underwent first and 36 patients who underwent second TSS as treatment for CD between 1990 and 2012. METHODS: Patients were divided into three groups according to remission status. Potential risk factors for recurrence, pituitary function, and strategy in persistent disease were assessed. RESULTS: THREE OUTCOME GROUPS WERE IDENTIFIED ACCORDING TO REMISSION STATUS AFTER FIRST TSS (MEAN FOLLOW-UP 79 MONTHS): remission, 71% (85/120), disease persistence, 29% (35/120), and disease recurrence, 34% (29/85) (mean time to recurrence 54 months). After second TSS (n=36, mean follow-up 62 months), we documented remission in 42% (15/36), disease persistence in 58% (21/36), and disease recurrence in 40% (6/15) (mean time to recurrence 42 months). Postoperative hypocortisolism after first, though not after second, TSS was associated with a lower risk of suffering disease recurrence (risk=0.72; 95% CI 0.60-0.88; exact significance (two-sided) P=0.035). CONCLUSIONS: Our study shows higher recurrence rates of CD after first TSS than previously reported. Second TSS leads an additional 8% of the patients to long term CD remission. PMID- 24217940 TI - Pemphigus foliaceus associated with anti-NXP2 autoantibody-positive dermatomyositis. PMID- 24217938 TI - The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial. AB - PURPOSE: The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. METHODS: The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of >=1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. RESULTS: A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 +/- 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 +/- 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose. CONCLUSION: Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome. PMID- 24217941 TI - Management of dabigatran-induced bleeding: expert statement. AB - The interdisciplinary group of experts has compiled a clinical guidance for manifest dabigatran-induced haemorrhage and envisaged invasive interventions on patients under dabigatran. It recommends an escalation of treatment measures as summarized in a pocket guide (see electronic supplementary material online and insert in the print issue). PMID- 24217942 TI - Circulating microRNA 122 in the methionine and choline-deficient mouse model of non-alcoholic steatohepatitis. AB - Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline-deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver-specific microRNA-122 (miR-122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR-122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR-122 levels were quantified in serum using RT-qPCR. Both miR-122 and ALT/AST levels were significantly elevated in serum at all timepoints. MiR-122 levels increased on average by 40-fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8- and 3.3-fold, respectively. In general, miR-122 levels remained elevated across all time points, whereas the ALT/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR-122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD associated liver injury in mouse efficacy models. PMID- 24217943 TI - The EORTC emotional functioning computerized adaptive test: phases I-III of a cross-cultural item bank development. AB - BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is currently developing computerized adaptive testing measures for the Quality of Life Questionnaire Core-30 (QLQ-C30) scales. The work presented here describes the development of an EORTC item bank for emotional functioning (EF), which is one of the core domains of the QLQ-C30. METHODS: According to the EORTC guidelines on module development, the development of the EF item bank comprised four phases, of which the phases I-III are reported in the present paper. Phase I involved defining the theoretical framework for the EF item bank and a literature search. Phase II included pre-defined item selection steps and a multi-stage expert review process. In phase III, feedback from cancer patients from different countries was obtained. RESULTS: On the basis of literature search in phase I, a list of 1750 items was generated. These were reviewed and further developed in phase II with a focus on relevance, redundancy, clarity, and difficulty. The development and selection steps led to a preliminary list of 41 items. In phase III, patient interviews (N = 41; Austria, Denmark, Italy, and the UK) were conducted with the preliminary item list, resulting in some minor changes to item wording. The final list comprised 38 items. DISCUSSION: The phases I-III of the developmental process have resulted in an EF item list that was well accepted by patients in several countries. The items will be subjected to larger-scale field testing in order to establish their psychometric characteristics and their fit to an item response theory model. PMID- 24217944 TI - Tumor endothelial marker imaging in melanomas using dual-tracer fluorescence molecular imaging. AB - PURPOSE: Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations. PROCEDURES: Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system. RESULTS: The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors. CONCLUSIONS: This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo. PMID- 24217945 TI - 6-[18F]fluoro-L-DOPA uptake in the rat pancreas is dependent on the tracer metabolism. AB - PURPOSE: 6-[(18)F]fluoro-L-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) positron emission tomography (PET) is a diagnostic tool which can detect malignancies of the pancreas. We aimed to study whether the manipulation of the [(18)F]FDOPA metabolic pathway would change the (18)F-behavior to provide a biochemical foundation for PET imaging of rat pancreas with [(18)F]FDOPA. PROCEDURES: Inhibitors of aromatic amino acid decarboxylase, catechol-O-methyltransferase, monoamine oxidases A and B, or their combinations on [(18)F]FDOPA uptake, metabolism, and the regional distribution in the rat pancreas was evaluated using in vivo PET/computed tomography imaging, chromatographic metabolite analyses, and autoradiography. RESULTS: Enzyme inhibition generally increased the uptake of [(18)F]FDOPA derived (18)F-radioactivity in rat pancreas. Dependent on which enzymatic pathway is blocked (or a combination of pathways), different radiolabeled metabolites in pancreas are responsible for this increase in uptake. CONCLUSIONS: Altering the metabolism of [(18)F]FDOPA by using various enzymatic inhibitors increased the radioactivity uptake and changed the radiometabolic profile in the pancreas allowing better discrimination between pancreas and surrounding tissues of rat. However, these manipulations did not separate islets from the exocrine pancreas. Elucidating the metabolic behavior of [(18)F]FDOPA provides a biochemical foundation of PET imaging of the rat pancreas. PMID- 24217946 TI - Fully automated trace level determination of parent and alkylated PAHs in environmental waters by online SPE-LC-APPI-MS/MS. AB - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous compounds that enter the environment from natural and anthropogenic sources, often used as markers to determine the extent, fate, and potential effects on natural resources after a crude oil accidental release. Gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction (LLE+GC-MS) has been extensively used to isolate and quantify both parent and alkylated PAHs. However, it requires labor-intensive extraction and cleanup steps and generates large amounts of toxic solvent waste. Therefore, there is a clear need for greener, faster techniques with enough reproducibility and sensitivity to quantify many PAHs in large numbers of water samples in a short period of time. This study combines online solid-phase extraction followed by liquid chromatography (LC) separation with dopant-assisted atmospheric pressure photoionization (APPI) and tandem MS detection, to provide a one-step protocol that detects PAHs at low nanograms per liter with almost no sample preparation and with a significantly lower consumption of toxic halogenated solvents. Water samples were amended with methanol, fortified with isotopically labeled PAHs, and loaded onto an online SPE column, using a large volume sample loop with an auxiliary LC pump for sample preconcentration and salt removal. The loaded SPE column was connected to an UPLC pump and analytes were backflushed to a Thermo Hypersil Green PAH analytical column where a 20-min gradient separation was performed at a variable flow rate. Detection was performed by a triple-quadrupole MS equipped with a gas-phase dopant delivery system, using 1.50 mL of chlorobenzene dopant per run. In contrast, LLE+GC-MS typically use 150 mL of organic solvents per sample, and methylene chloride is preferred because of its low boiling point. However, this solvent has a higher environmental persistence than chlorobenzene and is considered a carcinogen. The automated system is capable of performing injection, online SPE, inorganic species removal, LC separation, and MS/MS detection in 28 min. Selective reaction monitoring was used to detect 28 parent PAHs and 15 families of alkylated PAHs. The methodology is comparable to traditional GC-MS and was tested with surface seawater, rainwater runoff, and a wastewater treatment plant effluent. Positive detections above reporting limits are described. The virtual absence of sample preparation could be particularly advantageous for real-time monitoring of discharge events that introduce PAHs into environmental compartments, such as accidental releases of petroleum derivates and other human-related events. This work covers optimization of APPI detection and SPE extraction efficiency, a comparison with LLE+GC-MS in terms of sensitivity and chromatographic resolution, and examples of environmental applications. PMID- 24217947 TI - The use of immobilised metal affinity chromatography (IMAC) to compare expression of copper-binding proteins in control and copper-exposed marine microalgae. AB - Toxicity of metals to aquatic organisms is dependent on both external factors, such as exposure concentration and water quality parameters, and intracellular processes including specific metal-binding sites and detoxification. Current models used to predict copper toxicity in microalgae do not adequately consider these intracellular processes. This study compared the copper-binding proteins from four species of marine microalgae, Dunaliella tertiolecta, Tetraselmis sp., Phaedactylum tricornutum and Ceratoneis closterium, in controls (no added copper) and following a 72-h exposure to copper (sufficient to inhibit growth by approximately 50%). Cells were lysed by sonication, which was optimised to obtain 54-94% cell rupture for the different algae. Cell lysates were processed by immobilised metal affinity chromatography (IMAC) using Cu(2+) as the bound metal (i.e. Cu-IMAC). Bound proteins were subsequently analysed by SDS-PAGE, comparing proteins recovered from algae that were exposed to copper versus untreated control cells. Individual proteins for which copper exposure resulted in changes to proteins present were excised from gels and further analysed by nano LC ESI MS/MS; proteins were identified using the Mascot database. Proteins identified in this way included heat-shock proteins, rubisco, alpha- and beta-tubulins and ATP synthase (beta subunit). The results established that Cu-IMAC is a useful approach to identify proteins involved in copper binding in algae. This study identified several proteins that may play an active role in responses to copper toxicity in marine microalgae. PMID- 24217948 TI - Identification of proteins interacting with ammodytoxins in Vipera ammodytes ammodytes venom by immuno-affinity chromatography. AB - In order to perform their function, proteins frequently interact with other proteins. Various methods are used to reveal protein interacting partners, and affinity chromatography is one of them. Snake venom is composed mostly of proteins, and various protein complexes in the venom have been found to exhibit higher toxicity levels than respective components separately. Complexes can modulate envenomation activity of a venom and/or potentiate its effect. Our previous data indicate that the most toxic components of the Vipera ammodytes ammodytes (Vaa) venom isolated so far-ammodytoxins (Atxs)-are contributing to the venom's toxicity only moderately; therefore, we aimed to explore whether they have some interacting partner(s) potentiating toxicity. For screening of possible interactions, immuno-affinity chromatography combined with identification by mass spectrometry was used. Various chemistries (epoxy, carbonyldiimidazole, ethylenediamine) as well as protein G functionality were used to immobilize antibodies on monolith support, a Convective Interaction Media disk. Monoliths have been demonstrated to better suit the separation of large biomolecules. Using such approach, several proteins were indicated as potential Atx-binding proteins. Among these, the interaction of Atxs with a Kunitz-type inhibitor was confirmed by far-Western dot-blot and surface plasmon resonance measurement. It can be concluded that affinity chromatography on monolithic columns combined with mass spectrometry identification is a successful approach for screening of protein interactions and it resulted with detection of the interaction of Atx with Kunitz type inhibitor in Vaa venom for the first time. PMID- 24217949 TI - Incidence of adverse cardiac events 5 years after polymer-free sirolimus eluting stent implantation: Results from the prospective Bad Berka Yukon ChoiceTM registry. AB - OBJECTIVES: Drug-eluting stents (DES) constitute a major achievement in preventing re-stenosis, concerns remain regarding the increased inflammatory responses associated with the polymers used. This analysis focuses on outcomes in patients receiving the polymer-free sirolimus-eluting stent system YUKON-Choice (Yukon-DES, Translumina, Germany). METHODS: From 01/2006-09/2008 all patients receiving Yukon-DES (>=2.5 mm diameter) were prospectively enrolled in our registry. The primary endpoint was long-term major adverse cardiac events (MACE). RESULTS: 701 patients were included in our registry. Mean age was 65.7 +/- 10 years (73% male gender, 35.5% diabetes, and 32.2% acute coronary syndrome). 76% of the lesions were of Type B2/C. Lesion length was 24.6 +/- 5.2 mm and mean stent diameter was 2.8 +/- 0.4 mm. A total of 511 pts (72%) underwent 6-months angiographic follow-up, target vessel revascularization was noted in 23.5%. At 5 years clinical outcomes were: cardiac death 5.8%; myocardial infarction 3.4%; and TVR 24.6%. The incidence of MACE differed significantly between "on-label" and "off-label" indications (14.8% vs. 40.8% MACE; P < 0.001). Incidence of definitive/probable stent thrombosis (ST) was 1.14% (8/701); very late (>1 year) ST occurred in 0.29%. CONCLUSION: Our data suggests that the implantation of the sirolimus-coated polymer-free YUKON-DES is safe and feasible with a very low incidence of ST in this real world patient cohort with high percentage of diabetes and small vessels. PMID- 24217950 TI - Ligand-dependent activation of EphA4 signaling regulates the proteolysis of amyloid precursor protein through a Lyn-mediated pathway. AB - Alzheimer's disease is the most common dementia afflicting the elderly in modern society. This disease arises from the neurotoxicity elicited by abnormal aggregates of amyloid-beta (Abeta) protein. Such aggregates form through the cleavage of amyloid precursor protein (APP) by beta-secretase and the subsequent proteolysis of the APP C-terminal fragment (APP-betaCTF or C99) by gamma secretase to yield Abeta and APP intracellular domain (AICD). Recent evidence suggests that C99 and AICD may exert harmful effects on cells, suggesting that the proteolytic products of APP, including Abeta, C99, and AICD, could play a pivotal role in neuronal viability. Here, we demonstrate that ligand-activated EphA4 signaling governs the proteostasis of C99, AICD, and Abeta, without significantly affecting gamma-secretase activity. EphA4 induced accumulation of C99 and AICD through a Lyn-dependent pathway; activation of this pathway triggered phosphorylation of EphA4, resulting in positive feedback of C99 and AICD proteostasis. Inhibition of EphA4 by dasatinib, a receptor tyrosine kinase inhibitor, effectively suppressed C99 and AICD accumulation. Furthermore, EphA4 signaling controlled C99 and AICD proteolysis through the ubiquitin-proteasome system. In conclusion, we have identified an EphA4-Lyn pathway that is essential for the metabolism of APP and its proteolytic derivatives, thereby providing novel pharmacological targets for the development of anti-Abeta therapeutics for AD. PMID- 24217951 TI - Women's perceptions of sexual exploitability cues and their link to sexual attractiveness. AB - Two studies examined women's perception of the relationship between sexual exploitability and sexual attractiveness and women's use of cues to sexual exploitability to signal sexual accessibility. Study 1 (N = 77) found that women accurately assessed other women displaying cues to sexual exploitability both as sexually exploitable and sexually attractive to men. Study 2 (N = 74) tested the predictions that women who were dispositionally inclined toward short-term mating, who were not in a committed relationship, and who perceived themselves to be low in mate value would be more likely to display cues to sexual exploitability as a mate attraction tactic. Results supported the first prediction. These results suggest that a subset of women, those dispositionally inclined toward a short-term mating strategy, employ the risky strategy of signaling sexual accessibility using cues to exploitability to advance their mating goals. PMID- 24217952 TI - Four functions for four relationships: consensus definitions of university students. AB - In this study (N = 192; 124 women, 68 men), consensus definitions of one-night stands, booty-call relationships, friends-with-benefits, and serious romantic relationships were fashioned using a sample of university students. Participants provided a Likert and forced-choice assessment of how each relationship was characterized by the functions of sexual gratification, trial run, placeholder, and socioemotional support. Serious romantic relationships were primarily used to gain socioemotional support. Friends-with-benefits relationships were motivated by seeking a placeholder until someone better came along and as a trial run for a more serious relationship. Booty-call relationships and one-night stands were motivated primarily by a desire for sexual gratification. Men ascribed a greater range of reasons to engage in sexual relationships than women did and the more short-term the relationship was in nature, the greater the emergence of sex differences in ascribed functions. PMID- 24217953 TI - The effects of sexual partnership and relationship characteristics on three sexual risk variables in young men who have sex with men. AB - Young men who have sex with men (YMSM) in the United States are experiencing an alarming increase in HIV incidence. Recent evidence suggests that the majority of new HIV infections in YMSM occur in the context of serious relationships, which underscores the importance of examining predictors of sexual risk behavior in the context of sexual partnerships, including relationship type, sexual partner characteristics, and relationship dynamics. The current study aimed to evaluate relationship and sexual partnership influences on sexual risk behavior in YMSM, including differentiating between multiple sexual risk variables (i.e., any unprotected anal or vaginal intercourse, unprotected insertive anal or vaginal intercourse, and unprotected receptive anal intercourse). More serious/familiar partnerships were associated with more sexual risk across all three risk variables, while wanting a relationship to last was protective against risk across all three risk variables. Some variables were differentially linked to unprotected insertive sex (partner gender) or unprotected receptive sex (partner age, partner race, believing a partner was having sex with others, and partners repeated across waves). Sexual risk behavior in YMSM is inconsistent across sexual partnerships and appears to be determined in no small part by sexual partner characteristics, relationship dynamics, and sexual role (i.e., insertive or receptive partner). These influences are critical in understanding sexual risk in YMSM and provide important targets for intervention. PMID- 24217954 TI - Stress-induced cardiomyopathy and psychological wellbeing 1 year after an acute event. AB - Stress cardiomyopathy (SCM) typically presents similar symptoms to acute myocardial infarction (AMI). However, these symptoms differ when it comes to a transient and completely reversible myocardial dysfunction, which is frequently precipitated by acute stressful events, occurring in the absence of plaque rupture and coronary thrombosis. The purpose of this study was to investigate health-related quality of life (HRQL) and emotional burden subsequent to cardiac events in SCM patients. Thirty-seven SCM patients were compared with 37 matched AMI patients. All selected patients were assessed for HRQL and psychological distress at baseline and 1-year after the acute event. After controlling for covariates, scores on the Psychological General Well Being Index indicated that depressed mood had increased in both groups, but the increase for SCM patients was greater than for AMI patients. The AMI group displayed greater decreases than the SCM in physical quality of life and in total cardiac-related health quality of life. The percentage of patients with psychological distress increased significantly more in the SCM group than in the AMI group, and it made no difference whether the triggering event was emotional or physical. Our results suggest that, despite the more favorable medical prognosis of SCM patients, their cardiac condition being transient and resolving completely in few weeks, the psychological impact associated with their condition is more negative 1 year later than in the case of AMI patients whose medical prognosis is less favorable, and this difference is independent of type of trigger event. PMID- 24217955 TI - Adolescents' use of alcohol, tobacco and illicit drugs in relation to prenatal alcohol exposure: modifications by gender and ethnicity. AB - AIMS: The study aimed to investigate (a) the association between low to moderate prenatal alcohol exposure (PAE) and the use of alcohol, tobacco and illicit drugs in adolescence and (b) whether the associations are modified by gender and ethnicity. METHODS: The subjects of the study were 5922 children and adolescents, aged from 11 to 17 years, enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (the KiGGS study). Information on PAE is based on parental self-report questionnaires. Use of alcohol, tobacco and illicit drugs was assessed through self-report questionnaires for adolescents. RESULTS: Low to moderate PAE was associated with an increased risk of drinking alcohol (adjusted odds ratio (OR) 1.73, 95% confidence interval (CI) 1.34, 2.18) and also of illicit drug use (adjusted OR 1.62, 95% CI 1.23, 2.14). The associations between PAE and the use of alcohol, tobacco and illicit drugs differed according to gender and ethnicity. Gender stratified analyses resulted in adverse effects of PAE on drinking alcohol, smoking and illicit drug use in females; however, in German males, the associations disappeared. Stronger associations between PAE and the outcome measures were found in non-Germans. CONCLUSIONS: Our findings indicate that low to moderate levels of maternal alcohol intake during pregnancy are a risk factor for use of alcohol, tobacco and illicit drugs by the offspring, with stronger associations in females and non-Germans. PMID- 24217956 TI - Why adolescents are at risk of misusing alcohol and gambling. AB - AIMS: The aim of the study was to explore the reasons for alcohol misuse and other risk-taking behaviours in adolescence. METHODS: Narrative review. RESULTS: Vulnerable adolescents make suboptimal addictive-related choices in the period of initiation of alcohol use and gambling, which is also a period of cognitive and brain development, and in health behaviours. Hyperactive response to rewards as well as possibly hypoactive responses to punishments combined with weaknesses in the abilities to regulate strong impulses results in greater risk of alcohol and gambling misuse. CONCLUSION: Abnormal patterns of alcohol consumption (e.g. binge drinking) could dramatically reinforce this disequilibrium by enhancing salience for alcohol and associated information and compromising self-regulatory processes. There are some preventive and therapeutic cognitive training strategies that can strengthen willpower in adolescents. PMID- 24217957 TI - Notch1-nuclear factor kappaB involves in oxidative stress-induced alcoholic steatohepatitis. AB - AIMS: The Notch1 signaling pathway is implicated in multiple inflammatory diseases. However, the role of Notch1 signaling in alcoholic steatohepatitis (ASH) has not been fully investigated. We aimed to determine whether Notch1 Nuclear factor-kappaB (NF-kappaB) signaling mediates oxidative stress-induced ASH. METHODS: In vitro, three cell lines were used: the HepG2 cells, HepG2 cells transfected with a control vector (Neo cells) and HepG2 cells transfected with a cytochrome P4502E1-expression vector (2E1 cells), which allows the cells to undergo oxidative stress in response to ethanol. All three cell lines were incubated with ethanol with/without Notch1 inhibitor treatment, oxidative stress marker, steatohepatitis marker and Notch1-NF-kappaB signaling were assessed. To further test Notch1-NF-kappaB signaling in vivo, rats were fed with ethanol, ethanol plus Notch1 inhibitor or an isocaloric diet for 8 weeks. Hepatitis, oxidative stress and Notch1-NF-kappaB activity in the liver were assessed to further verify the in vitro results. RESULTS: Ethanol was shown to induce oxidative stress and steatohepatitis with remarkably elevated Notch1-NF-kappaB expression in 2E1 cells rather than HepG2 and Neo cells. Notch1 inhibitor was non toxic in the three cell lines and had a protective effect against markers of ASH. Similarly, chronic alcohol administration in vivo induced alcoholic hepatitis, oxidative stress and elevated Notch1-NF-kappaB expression in rats, while Notch1 inhibitor attenuated alcoholic liver injury. CONCLUSION: These findings provide direct in vitro and in vivo evidence that the oxidative stress-induced ASH is mediated by the Notch1-NF-kappaB signaling pathway, which can be effectively reversed by Notch1 inhibitor. PMID- 24217958 TI - Neuroimmune activation and myelin changes in adolescent rats exposed to high-dose alcohol and associated cognitive dysfunction: a review with reference to human adolescent drinking. AB - AIMS: The aim of the study was to assess whether intermittent ethanol administration to adolescent rats activates innate immune response and TLRs signalling causing myelin disruption and long-term cognitive and behavioural deficits. METHODS: We used a rat model of intermittent binge-like ethanol exposure during adolescence. RESULTS: Binge-like ethanol administration to adolescent rats increased the gene expression of TLR4 and TLR2 in the prefrontal cortex (PFC), as well as inflammatory cytokines TNFalpha and IL-1beta. Up regulation of TLRs and inflammatory mediators were linked with alterations in the levels of several myelin proteins in the PFC of adolescent rats. These events were associated with previously reported long-term cognitive dysfunctions. Conversely, the same ethanol treatment did not cause significant changes in either inflammatory mediators or myelin changes in the brain of adult rats. CONCLUSION: Activation of innate immune receptors TLRs in the PFC appears to be involved in the neuroinflammation and demyelination processes induced by ethanol exposure during adolescence. The findings support the vulnerability of the juvenile brain to the effects of ethanol and the long-term cognitive consequences of binge drinking. In addition, ethanol-induced PFC dysfunctions might underlie the propensity of adolescents for impulsivity and to ignore the negative consequences of their behaviour, both of which could increase the risk of substance abuse. PMID- 24217960 TI - Obituary Prof. Dr. Walter Marget. PMID- 24217959 TI - Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case control analysis. AB - PURPOSE: From mid-2010 to early 2013 there was a large single-center (Leipzig University Hospital, Germany) outbreak of Klebsiella pneumoniae carbapenemase (KPC) type 2 producing K. pneumoniae (KPC-2-KP) involving a total of 103 patients. The aim of this study was to compare KPC-positive liver transplant recipients (LTR) and KPC-negative controls to determine both the relative risk of infection following colonization with KPC-2-KP and the case fatality rate associated with KPC-2-KP. METHODS: The study cohort of this retrospective observational study comprised nine patients who had undergone orthotopic liver transplantation (LTx) (median age of 52 years, range 28-73 years) with confirmed evidence of colonization with KPC-2-KP. The data from these nine LTR were matched to 18 LTR (1:2) in whom carbapenem-resistant pathogens were not present and compared for clinical outcomes. RESULTS: Of these nine cases, eight (89 %) progressed to infection due to KPC-2-KP, and five (56 %) were confirmed to have bloodstream infection with KPC-2-KP. Matched-pair analysis of KPC-positive LTR and KPC-negative controls revealed a substantially increased relative risk of 7.0 (95 % confidence interval 1.8-27.1) for fatal infection with KPC-2-producing K. pneumoniae after transplantation with a mortality rate of 78 % (vs. 11 %, p = 0.001). CONCLUSIONS: Colonization with KPC-2-KP in LTR leads to high infection rates and excess mortality. Therefore, frequent screening for carbapenem resistant bacteria in patients on LTx waiting lists appears to be mandatory in an outbreak setting. Patients with evidence of persistent colonization with KPC producing pathogens should be evaluated with extreme caution for LTx. PMID- 24217961 TI - Successful isavuconazole salvage therapy in a patient with invasive mucormycosis. AB - A 45-year-old male with rhinocerebral mucormycosis (Rhizopus oryzae), refractory to liposomal amphotericin B and posaconazole, received isavuconazole salvage therapy. Initial isavuconazole plasma and tissue levels were 0.76-0.86 MUg/mL and 1.09-1.38 MUg/g. Plasma levels increased to 1.3-3.24 MUg/mL with reduced comedication. Isavuconazole was well tolerated, and the patient has remained disease-free 24 months post-antifungal therapy. PMID- 24217962 TI - Is adult atopic eczema more common than we think? - A population-based study in Danish adults. PMID- 24217963 TI - Schwannomas, benign tumors with a senescent phenotype. AB - BACKGROUND: Schwannomas are benign nerve sheath tumors that only very rarely undergo malignant changes. Oncogenic-induced senescence is a defense mechanism against such malignant transformation. Different molecular pathways are involved in this process, such as RAS-RAF-MAPK. Based on the fact that the RAS-RAF-MAPK pathway is known to be activated in peripheral nerve sheath tumors, this study analyzes senescence markers in Schwannomas to demonstrate the possible role of senescence in their genesis. METHODS: A retrospective immunohistochemical study was done in 39 schwannoma and 18 malignant peripheral nerve sheath tumors (MPNST). Staining for p16INK4a, Ki67, p53 and CyclinD1 was performed in all the cases. Additionally, beta-galactosidase staining was done in those cases in which frozen tissue was available (n=8). RESULTS: Higher levels of p16INK4a (p=0.0001) and lower levels of Ki67 (p=0.0001) were found in Schwannomas. Beta-galactosidase activity was positive in 5/5 Schwannomas and negative in 3/3 MPNST. CONCLUSIONS: Our results support the senescence nature of Schwannomas and the absence of a senescence phenotype in MPNST. PMID- 24217965 TI - A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma. AB - BACKGROUND: The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. METHODS: A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (<24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. RESULTS: A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. CONCLUSIONS: We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis. PMID- 24217964 TI - Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors. AB - BACKGROUND: Although mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, controversy remains regarding the engraftment, proliferation, and differentiation for repopulating MSCs in recipient tissues. Therefore, we investigated the paracrine and/or endocrine role of MSCs in experimental colitis. METHODS: We analyzed the therapeutic effects of MSC conditioned medium (MSC-CM) on dextran sulfate sodium (DSS)- or 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis. We investigated the effects of MSC-CM on the epithelial cell viability, mobility, cell cycle, and cytokine production in ex vivo lamina propria/mesenteric lymphocytes, a macrophage cell line, and the mixed lymphocyte reaction. An optimal regimen against colitis was explored. The contents of MSC-CM were analyzed using a WNT signaling pathway polymerase chain reaction array, an inflammatory cytokines antibody array, and liquid chromatography-tandem mass spectrometry analysis. RESULTS: Independent of the systemic administration route, MSC-CM concentrates were effective for the inductive phase of TNBS-induced colitis and for the recovery phase of DSS-induced colitis. Hypoxia appeared to be one of the optimal preconditioning factors assessed by cell motility and viability through activating the PI3K-Akt pathway in rat small intestine epithelial cells, IEC-6. Thus, Hypoxia had profound effects on the contents of MSC-CM, which comprised pleiotropic gut trophic factors involved in each wound healing process, including the anti-inflammatory, proliferative, and tissue remodeling phases. CONCLUSIONS: Identification and optimization of potential gut trophic factors in MSC-CM is urgently needed to form the basis for new drug discovery and for optimizing cell-based therapies for inflammatory bowel disease. PMID- 24217966 TI - Disparities in mental health outcomes among lung cancer survivors associated with ruralness of residence. AB - OBJECTIVE: Healthy People 2020 identifies elimination of health disparities as a key aim. Rural residence is associated with disparities in cancer screening, physical morbidity, and survival. The present study aimed to identify potential disparities in mental health (MH) outcomes (e.g., anxiety and depression symptoms, distress) in lung cancer (LC) survivors associated with ruralness of residence. METHODS: Lung cancer survivors (LC group; n = 193; mean age = 63.1 years; mean time since diagnosis = 15.6 months) were recruited from the population-based SEER Kentucky Cancer Registry. LC survivors completed a telephone interview and questionnaire assessing MH outcomes. U.S. Department of Agriculture Rural-Urban Continuum Codes were used to identify Rural (n = 117) and Urban (n = 76) LC survivors. A healthy comparison (HC) group was recruited (n = 152) and completed a questionnaire assessing MH outcomes. RESULTS: Across six MH indices, Rural LC survivors reported poorer MH relative to Urban LC survivors with a mean effect size (ES) of 0.43 SD in unadjusted analyses and 0.29 SD in analyses adjusted for education and physical comorbidity. Comparison of the LC and HC groups revealed significant Ruralness * Group interactions for five of six MH indices. The Rural LC group reported poorer MH than the Rural HC group with a mean ES of 0.51 SD. The MH of Urban LC and HC groups did not differ (mean ES = 0.00 SD). CONCLUSIONS: Rural residence is a risk factor for poorer MH outcomes for LC survivors. The MH of Rural LC survivors may be more negatively impacted by cancer diagnosis and treatment than the MH of Urban LC survivors. PMID- 24217967 TI - UV-visible light-activated Ag-decorated, monodisperse TiO2 aggregates for treatment of the pharmaceutical oxytetracycline. AB - Noble metal Ag-decorated, monodisperse TiO2 aggregates were successfully synthesized by an ionic strength-assisted, simple sol-gel method and were used for the photocatalytic degradation of the antibiotic oxytetracycline (OTC) under both UV and visible light (UV-visible light) irradiation. The synthesized samples were characterized by X-ray diffraction analysis (XRD); UV-vis diffuse reflectance spectroscopy; environmental scanning electron microscopy (ESEM); transmission electron microscopy (TEM); high-resolution TEM (HR-TEM); micro Raman, energy-dispersive X-ray spectroscopy (EDS); and inductively coupled plasma optical emission spectrometry (ICP-OES). The results showed that the uniformity of TiO2 aggregates was finely tuned by the sol-gel method, and Ag was well decorated on the monodisperse TiO2 aggregates. The absorption of the samples in the visible light region increased with increasing Ag loading that was proportional to the amount of Ag precursor added in the solution over the tested concentration range. The Brunauer, Emmett, and Teller (The BET) surface area slightly decreased with increasing Ag loading on the TiO2 aggregates. Ag decorated TiO2 samples demonstrated enhanced photocatalytic activity for the degradation of OTC under UV-visible light illumination compared to that of pure TiO2. The sample containing 1.9 wt% Ag showed the highest photocatalytic activity for the degradation of OTC under both UV-visible light and visible light illumination. During the experiments, the detected Ag leaching for the best TiO2 Ag photocatalyst was much lower than the National Secondary Drinking Water Regulation for Ag limit (0.1 mg L(-1)) issued by the US Environmental Protection Agency. PMID- 24217968 TI - Comparative tolerance of Pinus radiata and microbial activity to copper and zinc in a soil treated with metal-amended biosolids. AB - A study was conducted to evaluate the effects of elevated concentrations of copper (Cu) and zinc (Zn) in a soil treated with biosolids previously spiked with these metals on Pinus radiata during a 312-day glasshouse pot trial. The total soil metal concentrations in the treatments were 16, 48, 146 and 232 mg Cu/kg or 36, 141, 430 and 668 mg Zn/kg. Increased total soil Cu concentration increased the soil solution Cu concentration (0.03-0.54 mg/L) but had no effect on leaf and root dry matter production. Increased total soil Zn concentration also increased the soil solution Zn concentration (0.9-362 mg/L). Decreased leaf and root dry matter were recorded above the total soil Zn concentration of 141 mg/kg (soil solution Zn concentration, >4.4 mg/L). A lower percentage of Cu in the soil soluble + exchangeable fraction (5-12 %) and lower Cu(2+) concentration in soil solution (0.001-0.06 MUM) relative to Zn (soil soluble + exchangeable fraction, 12-66 %; soil solution Zn(2+) concentration, 4.5-4,419 MUM) indicated lower bioavailability of Cu. Soil dehydrogenase activity decreased with every successive level of Cu and Zn applied, but the reduction was higher for Zn than for Cu addition. Dehydrogenase activity was reduced by 40 % (EC40) at the total solution-phase and solid-phase soluble + exchangeable Cu concentrations of 0.5 mg/L and 14.5 mg/kg, respectively. For Zn the corresponding EC50 were 9 mg/L and 55 mg/kg, respectively. Based on our findings, we propose that current New Zealand soil guidelines values for Cu and Zn (100 mg/kg for Cu; 300 mg/kg for Zn) should be revised downwards based on apparent toxicity to soil biological activity (Cu and Zn) and radiata pine (Zn only) at the threshold concentration. PMID- 24217969 TI - Increased bioavailability of metals in two contrasting agricultural soils treated with waste wood-derived biochar and ash. AB - Recycled waste wood is being increasingly used for energy production; however, organic and metal contaminants in by-products produced from the combustion/pyrolysis residue may pose a significant environmental risk if they are disposed of to land. Here we conducted a study to evaluate if highly polluted biochar (from pyrolysis) and ash (from incineration) derived from Cu-based preservative-treated wood led to different metal (e.g., Cu, As, Ni, Cd, Pb, and Zn) bioavailability and accumulation in sunflower (Helianthus annuus L.). In a pot experiment, biochar at a common rate of 2 % w/w, corresponding to ~50 t ha( 1), and an equivalent pre-combustion dose of wood ash (0.2 % w/w) were added to a Eutric Cambisol (pH 6.02) and a Haplic Podzol (pH 4.95), respectively. Both amendments initially raised soil pH, although this effect was relatively short term, with pH returning close to the unamended control within about 7 weeks. The addition of both amendments resulted in an exceedance of soil Cu statutory limit, together with a significant increase of Cu and plant nutrient (e.g., K) bioavailability. The metal-sorbing capacity of the biochar, and the temporary increase in soil pH caused by adding the ash and biochar were insufficient to offset the amount of free metal released into solution. Sunflower plants were negatively affected by the addition of metal-treated wood-derived biochar and led to elevated concentration of metals in plant tissue, and reduced above- and below ground biomass, while sunflower did not grow at all in the Haplic Podzol. Biochar and ash derived from wood treated with Cu-based preservatives can lead to extremely high Cu concentrations in soil and negatively affect plant growth. Identifying sources of contaminated wood in waste stream feedstocks is crucial before large-scale application of biochar or wood ash to soil is considered. PMID- 24217970 TI - Bioaccumulation of butyltins and liver damage in the demersal fish Cathorops spixii (Siluriformes, Ariidae). AB - The toxicity of butyltin compounds (BTs), mainly tributyltin (TBT), has been reported in different organisms. However, such an analysis in fish after field exposure with reference to the related biomarkers has not been commonly observed in the literature. This study presents the uptake of BTs in the liver of a neotropical marine catfish Cathorops spixii in Paranagua Bay, an important estuarine system located in southern Brazil. Two different areas, close to and distant from the harbor, were used for chemical analysis evaluation of hepatotoxicity through genetic, enzymatic, and histopathological biomarkers. The presence of polycyclic aromatic hydrocarbons in bile was also considered as a biomarker. The results showed a significant relationship between TBT levels and the inhibition of biotransformation enzymes and high occurrence of melanomacrophages in fish collected close to the harbor site. These effects were linked to the absence of TBT metabolites in the liver. In the second site, the presence of DBT was associated with an increase in EROD and GST activity. The larger amount of DNA damage as well as the highest oxidative stress was noted in fish from the less TBT-polluted area, where DBT and bile PAHs occurred. These findings showed different impact levels due to or increased by the chronic exposure of biota to BTs. PMID- 24217971 TI - Optimization of struvite fertilizer formation from baker's yeast wastewater: growth and nutrition of maize and tomato plants. AB - Struvite precipitate obtained from yeast industry anaerobic effluent with high ammonium nitrogen (NH4-N) was investigated for fertilizer effect on plant growth and nutrition according to applications of N, nitrogen/phosphorus/potassium (NPK), and control. Optimum struvite formation conditions were determined via Box Behnken design. Optimum condition was obtained at pH 9.0 and Mg/N/P molar ratio of 1.5:1:1. Under these conditions, heavy metal concentrations in the obtained struvite precipitate (except Cu) were below the detection limits. In addition to high N, P, and Mg content, energy-dispersive X-ray (EDX) analysis showed that the struvite also included the nutritional elements Ca, K, Na, and Fe. X-ray diffraction (XRD) analysis revealed the complex structures of NaAl(SO4)2(H2O)12, NaMn(2+)Fe2(PO4)3, and (Na2,Ca)O2(Fe,Mn)O.P2O5 in the precipitate. High Na(+) and Ca(2+) concentrations in the anaerobic effluent reacted with phosphate during struvite precipitation. Different applications and struvite dosages significantly affected fresh and dry weights and nutrient element uptakes by plants (P < 0.05). N, P, and Mg uptakes of plants were significantly higher at struvite *2, *3, and *4 dosages compared with NPK application. For adequate nutrition and supply of optimum dry weight, struvite *2 dosage (5.71 g struvite/kg soil) was found appropriate for both maize and tomato plants. PMID- 24217972 TI - A short-term study to evaluate the uptake and accumulation of arsenic in Asian willow (Salix sp.) from arsenic-contaminated water. AB - Five Asian willow species (Salix jiangsuensis J172, Salix matsudana, Salix integra Yizhibi, Salix integra Weishanhu, and Salix mongolica) were evaluated for their potential for phytofiltration of arsenic (As) from synthetically contaminated waters. Arsenic accumulation, tolerance, uptake influx, and phytofiltration ability of the five willow species were examined under hydroponic conditions in a glasshouse. Short-term exposure (2 weeks) to solutions containing 80 MUmol L(-1) arsenate (As(V)), resulted in significant accumulation of As in all willow species. Arsenic concentration in plant roots ranged from 322 mg kg( 1) dry weight (DW) for S. matsudana to 604 mg kg(-1) (DW) for S. integra Yizhibi. S. integra Yizhibi decreased As(V) concentration in water from 3.87 to 1.89 MUmol L(-1) (290 to 142 MUg L(-1)) over 168 h, which is 50 % of the total As(V) in the solution. The results suggested that even though Asian willow was not a traditional aquatic species, it still had significant potential for phytofiltration of As from contaminated waters. Of the five willow species studied, S. integra Yizhibi had the greatest capacity to remove As from As contaminated waters. Thus, Asian willow has significant potential for the phytofiltration of As and may also be suitable for practical phytoremediation of As in highly water-logged areas. PMID- 24217973 TI - Biodegradation of low-ethoxylated nonylphenols in a bioreactor packed with a new ceramic support (Vukopor (r) S10). AB - This work was aimed at studying the possibility of biodegrading 4-nonylphenol and low ethoxylated nonylphenol mixtures, which are particularly recalcitrant to microbial degradation, by employing a biofilm reactor packed with a ceramic support (Vukopor(r) S10). A selected microbial consortium (Consortium A) was used to colonize the support. 4-Nonylphenol and ethoxylated nonylphenol degradation and mineralization capabilities were studied both in batch and continuous mode. The results showed that Vukopor(r) S10 was able to be colonized by an active biofilm for the degradation of the target pollutants with the reactor operating both in batch and continuous mode. On the other hand, pollutant adsorption on the support was negligible. FISH showed equal proportion of Alphaproteobacteria and Gammaproteobacteria in the Igepal CO-520 degrading reactor. A shift towards high proportion of Gammaproteobacteria was observed by supplying Igepal CO-210. PCR density gradient gel electrophoresis (DGGE) analyses also evidenced that the biofilm evolved with time by changing the mixture applied and that Proteobacteria were the most represented phylum in the biofilm. Taken together, the data obtained provide a strong indication that the biofilm reactor packed with Vukopor(r) S10 and inoculated with Consortium A could potentially be used to develop a technology for the decontamination of 4-nonylphenol and low ethoxylated nonylphenol polluted effluents. PMID- 24217974 TI - Proteomic analysis of differentially expressed proteins in 5-fluorouracil-treated human breast cancer MCF-7 cells. AB - BACKGROUND: 5-Fluorouracil (5-Fu) is a commonly used chemotherapeutic agent in clinical care of breast cancer patients. However, the mechanism of how the 5-Fu works is complex and still largely unknown. OBJECTIVE: The objective of this study was to understand the mechanism further and explore the new targets of 5 Fu. METHODS: The differentially expressed proteins induced by 5-Fu in human breast cancer MCF-7 cells were identified by proteomic analysis. Four differentially expressed proteins were validated using Western blot and quantitative real-time reverse-transcription polymerase chain reaction analysis for protein and mRNA levels. The effect of 5-Fu on MCF-7 cells was determined by cell viability assay, transmission electron microscopy and flow cytometry analysis. RESULTS: 5-Fu dose-dependently inhibited cell proliferation with the IC50 value of 98.2 MUM. 5-Fu also induced obviously morphological change and apoptosis in MCF-7 cells. Twelve differentially expressed proteins involved in energy metabolism, cytoskeleton, cellular signal transduction and tumor invasion and metastasis were identified. CONCLUSION: These results may provide a new insight into the molecular mechanism of 5-Fu in therapy of breast cancer. PMID- 24217975 TI - Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine. AB - PURPOSE: To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks. METHODS: We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system. RESULTS: Nine of the 37 patients (24 %) had >=2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5-8.3) for patients with CTC 0-1 as compared to 9.4 months (95 % CI 1.2-12.2) for those with CTC >=2 (p = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8-16.3) and 12.2 (95 % CI 1.4-12.2) months for patients with 0-1 CTCs and >=2 CTCs, respectively (p = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0-1 at baseline and CTC = 0-1 after second chemotherapy cycle (18 patients); group 2, CTC >=2 at baseline and CTC = 0-1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively (p = 0.4467). CONCLUSIONS: CTCs >=2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed. PMID- 24217976 TI - Voice-related modulation of mechanosensory detection thresholds in the human larynx. AB - Rapidly adapting mechanoreceptors within the laryngeal mucosa provide the central nervous system with perceptual and proprioceptive afference for a variety of essential yet diverse human functions including voice sound production and airway protection. It is unknown why mechanosensory information that yields a defensive response when an individual breathes may go largely unnoticed when the individual voices. Therefore, a central question is whether there is voice-related modulation of laryngeal mechanosensory detection. Such modulation would be consistent with current models of afferent laryngeal control, and may be important to maintain fluent voice in the presence of potentially distracting sensory input. Therefore, we employed endoscopic assessment of laryngeal mechanosensory detection thresholds in ten healthy adults during tidal breathing and a voice task. We tested the hypothesis that laryngeal mechanosensory detection thresholds would be higher during the voice task. We found that thresholds were significantly higher for all participants during the voice task and that these changes were significantly more modest in women. Our findings suggest that the laryngeal sensorium may modulate mechanosensory afference to attenuate the potentially distracting influence of sensory input during voice. The finding that women maintain a greater sensitivity during the voice task than men (lower thresholds) may have important implications for the higher prevalence of sensorimotor voice disturbances in women. Our results are consistent with the presence of mechanosensory modulation in other motor systems and with observed sensory differences between women and men. Such modulation has important implications for understanding the underlying neural mechanisms of laryngeal control and how these mechanisms may operate in individuals with laryngeal disturbances. PMID- 24217977 TI - Reciprocal interactions between the human thalamus and periaqueductal gray may be important for pain perception. AB - Pain perception can be altered by activity in the periaqueductal gray (PAG). The PAG can decrease the incoming nociceptive signals at the level of the spinal dorsal horn, but it is not clear whether the PAG can also affect the sensory thalamus, ventral posterolateral and ventral posteromedial thalamic nuclei, to modulate pain. However, the PAG and the thalamus have direct connections with each other; so we postulated that the PAG may also modulate pain by inhibiting the sensory nuclei in the thalamus, and that these may also reciprocally influence the PAG. Here, by analyzing the local field potentials recorded from the sensory thalamus and the PAG in chronic pain patients with deep brain stimulation electrodes, we show that PAG stimulation inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus stimulation excited the PAG with increasing PAG delta and theta power. We demonstrate that the PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation. PMID- 24217978 TI - YB-1 protein: functions and regulation. AB - The Y-box binding protein 1 (YB-1, YBX1) is a member of the family of DNA- and RNA-binding proteins with an evolutionarily ancient and conserved cold shock domain. It falls into a group of intrinsically disordered proteins that do not follow the classical rule 'one protein-one function' but introduce a novel principle stating that a disordered structure suggests many functions. YB-1 participates in a wide variety of DNA/RNA-dependent events, including DNA reparation, pre-mRNA transcription and splicing, mRNA packaging, and regulation of mRNA stability and translation. At the cell level, the multiple activities of YB-1 are manifested as its involvement in cell proliferation and differentiation, stress response, and malignant cell transformation. WIREs RNA 2014, 5:95-110. doi: 10.1002/wrna.1200 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. PMID- 24217979 TI - Does coronary CT angiography improve risk stratification over coronary artery calcium scoring in symptomatic patients with a low pre-test probability of coronary artery disease and a CAC of zero? PMID- 24217980 TI - Deformation patterns in genotyped patients with hypertrophic cardiomyopathy. AB - AIMS: Echocardiographic strain imaging with two-dimensional speckle tracking is an emerging tool for defining cardiac function and identifying preclinical hypertrophic cardiomyopathy (HCM). In HCM, a reverse septal contour is a strong predictor of mutation positive sarcomeric HCM. The objective of this study was to determine whether left ventricular (LV) deformation patterns can differentiate between genotype positive and negative patients within a large HCM cohort. METHODS AND RESULTS: One hundred and thirty one patients (89 males, age 55 +/- 15 years) with clinically diagnosed HCM underwent comprehensive transthoracic echocardiography inclusive of LV strain imaging, LV dimensions and ejection fraction, septal contour and thickness, and identification of obstructive physiology. Longitudinal peak systolic strain was assessed from 17 LV myocardial segments blinded to the patient's genetic test results derived from comprehensive genotyping of nine myofilament HCM-associated genes. Genotyping revealed that 51 of 131 patients (39%) were mutation positive for sarcomeric/myofilament-HCM (genotype positive). Regional strain was lower in genotype-positive patients in mid inferoseptal (P = 0.004), basal anteroseptal (P = 0.04), and basal inferoseptal segments (P = 0.002) compared with HCM patients lacking a mutation (genotype negative). Strain patterns in reverse-curve, genotype-positive HCM differed significantly from genotype negative, sigmoidal HCM in multiple segments. However, when comparing genotype-negative and genotype-positive patients with the same septal morphology, there were no significant regional strain differences. Septal thickness positively correlated with global and basal anteroseptal longitudinal strain (r = 0.34 and r = 0.54, respectively, P < 0.0001). CONCLUSION: Significant regional strain differences in genotyped HCM patients are dependent upon septal morphology or thickness, not genotype. Phenotypic expression of deformation patterns appears heterogeneous. PMID- 24217981 TI - 3-Nitrotoluene dioxygenase from Diaphorobacter sp. strains: cloning, sequencing and evolutionary studies. AB - The first step in the degradation of 3-nitrotoluene by Diaphorobacter sp. strain DS2 is the dihydroxylation of the benzene ring with the concomitant removal of nitro group. This is catalyzed by a dioxygenase enzyme system. We report here the cloning and sequencing of the complete dioxygenase gene with its putative regulatory sequence from the genomic DNA of Diaphorobacter sp. strains DS1, DS2 and DS3. Analysis of the 5 kb DNA stretch that was cloned, revealed five complete open reading frames (ORFs) encoding for a reductase, a ferredoxin and two dioxygenase subunits with predicted molecular weights (MW) of 35, 12, 50 and 23 kDa respectively. A regulatory protein was also divergently transcribed from the reductase subunit and has a predicated MW of 34 kDa. Presence of parts of two functional ORFs in between the reductase and the ferredoxin subunits reveals an evolutionary route from a naphthalene dioxygenase like system of Ralstonia sp. strain U2. Further a 100 % identity of its ferredoxin subunit reveals its evolution via dinitrotoluene dioxygenase like system present in Burkholderia cepacia strain R34. A modeled structure of oxygenase3NT from strain DS2 was generated using nitrobenzene dioxygenase as a template. The modeled structure only showed minor changes at its active site. Comparison of growth patterns of strains DS1, DS2 and DS3 revealed that Diaphorobacter sp. strain DS1 has been evolved to degrade 4-nitrotoluene better by an oxidative route amongst all three strains. PMID- 24217982 TI - Looking back and moving forward: an historical perspective from laboratory genetic counselors. AB - Despite a consistent increase in genetic counselors who report working in laboratory positions, there is a relative dearth of literature on laboratory genetic counseling. Semi-structured interviews were completed with nine laboratory genetic counselors to document how positions were created and have changed with time. Interview transcriptions were analyzed for emerging themes. Several common themes were identified, including that early positions were often part-time, laboratory-initiated and had a lack of job definition. Laboratory genetic counselors commented on their evolving roles and responsibilities, with their positions becoming more technical and specialized over time and many taking on managerial and supervisory roles. All genetic counselors surveyed reported using core genetic counseling skills in their positions. The expansion of diagnostic testing and quickly evolving technology were common themes in regards to the future of laboratory genetic counselors, and participants commented on laboratory genetic counselors having expanding roles with data management, result interpretation and reporting, and guidance of other healthcare providers. Other comments included the impact of competition among laboratories and how training programs can better prepare genetic counseling students for a career in the laboratory setting. This study describes the emergence, and subsequent evolution, of laboratory genetic counseling positions as a significant subspecialty of genetic counseling. PMID- 24217983 TI - Pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept in adult kidney transplant recipients. AB - BACKGROUND AND OBJECTIVES: Belatacept is a first-in-class, selective co stimulation blocker recently approved for the prophylaxis of organ rejection in adult kidney transplant recipients. The objective of this study was to report the pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept. METHODS: The pharmacokinetics, pharmacodynamics (CD86 receptor occupancy), and immunogenicity of belatacept were studied in de novo adult kidney transplant recipients in phase II and III clinical studies. RESULTS: Following multiple doses of 5 or 10 mg/kg, the geometric mean (percentage coefficient of variation) maximum serum concentration and area under the serum concentration-time curve over one dosing interval of belatacept were 136 (20%) and 238 (27%) MUg/mL, and 13,587 (27%) and 21,241 (35%) MUg.h/mL, respectively. The median belatacept elimination half-life was 8-9 days. Belatacept exhibited concentration-dependent binding to CD86 receptors. The pre-dose CD86 receptor occupancy by belatacept decreased from 94 to 65% between day 5 and 1 year post-transplant, with corresponding pre-dose trough serum concentrations of belatacept decreasing from ~35 to 4 MUg/mL during this period. The cumulative incidence of developing anti belatacept antibodies was 5.3% up to 3 years post-transplant and had no impact on belatacept exposure. CONCLUSIONS: Belatacept in adult kidney transplant demonstrated linear pharmacokinetics with low variability, concentration dependent pharmacodynamics, and a low incidence of anti-drug antibodies. PMID- 24217984 TI - Range of motion of thoracic spine in sagittal plane. AB - STUDY DESIGN: Imaging study of thoracic spine. OBJECTIVE: The purpose of this study was to investigate dynamic alignment and range of motion (ROM) at all segmental levels of thoracic spine. Thoracic spine is considered to have restricted ROM because of restriction by the rib cage. However, angular movements of thoracic spine can induce thoracic compressive myelopathy in some patients. Although few previous studies have reported segmental ROM with regard to sagittal plane, these were based on cadaver specimens. No study has reported normal functional ROM of thoracic spine. METHODS: Fifty patients with cervical or lumbar spinal disease but neither thoracic spinal disease nor compression fracture were enrolled prospectively in this study (34 males, 16 females; mean age 55.4 +/- 14.7 years; range 27-81 years). After preoperative myelography, multidetector-row computed tomography scanning was performed at passive maximum flexion and extension position. Total and segmental thoracic kyphotic angles were measured and ROM calculated. RESULTS: Total kyphotic angle (T1/L1) was 40.2 degrees +/- 11.4 degrees and 8.5 degrees +/- 12.8 degrees in flexion and extension, respectively (P < 0.0001). The apex of the kyphotic angle was at T6/7 in flexion. Total ROM (T1/L1) was 31.7 degrees +/- 11.3 degrees . Segmental ROM decreased from T1/2 to T4/5 but increased gradually from T4/5 to T12/L1. Maximum ROM was at T12/L1 (4.2 degrees +/- 2.1 degrees ) and minimum at T4/5 (0.9 degrees +/- 3.0 degrees ). CONCLUSIONS: Thoracic spine showed ROM in sagittal plane, despite being considered a stable region. These findings offer useful information in the diagnosis and selection of surgical intervention in thoracic spinal disease. PMID- 24217986 TI - Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. AB - BACKGROUND: Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009. OBJECTIVES: To provide an overview of the relative analgesic efficacy of antiepileptic drugs that have been compared with placebo in neuropathic pain and fibromyalgia, and to report on adverse events associated with their use. METHODS: We included reviews published in theCochrane Database of Systematic Reviews up to August 2013 (Issue 7). We extracted information from each review on measures of efficacy and harm, and methodological details concerning the number of participants, the duration of studies, and the imputation methods used, in order to judge potential biases in available data.We analysed efficacy data for each painful condition in three tiers, according to outcome and freedom from known sources of bias. The first tier met current best standards - at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) for dropouts, an intention-to-treat (ITT) analysis, in parallel group studies with at least 200 participants lasting eight weeks or more. The second tier used data from at least 200 participants where one or more of the above conditions were not met. The third tier of evidence related to data from fewer than 200 participants, or with several important methodological problems that limited interpretation. MAIN RESULTS: No studies reported top tier results.For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and postherpetic neuralgia. In addition, for pregabalin, we found evidence of efficacy in central neuropathic pain and fibromyalgia. Point estimates of numbers needed to treat for an additional beneficial effect (NNTs) were in the range of 4 to 10 for the important outcome of pain intensity reduction over baseline of 50% or more.For other antiepileptic drugs there was no evidence (clonazepam, phenytoin), so little evidence that no sensible judgement could be made about efficacy (valproic acid), low quality evidence likely to be subject to a number of biases overestimating efficacy (carbamazepine), or reasonable quality evidence indicating little or no effect (lamotrigine, oxcarbazepine, topiramate). Lacosamide recorded such a trivial statistical superiority over placebo that it was unreliable to conclude that it had any efficacy where there was possible substantial bias.Any benefits of treatment came with a high risk of adverse events and withdrawal because of adverse events, but serious adverse events were not significantly raised, except with oxcarbazepine. AUTHORS' CONCLUSIONS: Clinical trial evidence supported the use of only gabapentin and pregabalin in some neuropathic pain conditions (painful diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain) and fibromyalgia. Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. For other antiepileptic drugs there was no evidence, insufficient evidence, or evidence of a lack of effect; this included carbamazepine. Evidence from clinical practice and experience is that some patients can achieve good results with antiepileptics other than gabapentin or pregabalin.There is no firm evidence to answer the important pragmatic questions about which patients should have which drug, and in which order the drugs should be used. There is a clinical effectiveness research agenda to provide evidence about strategies rather than interventions, to produce the overall best results in a population, in the shortest time, and at the lowest cost to healthcare providers. PMID- 24217985 TI - Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. AB - Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers; canker sores) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. Up to now, the etiopathogenesis of this condition remains unclear; it is, however, considered to be multifactorial. The results of currently performed studies indicate that genetically mediated disturbances of the innate and acquired immunity play an important role in the disease development. Factors that modify the immunologic response in RAS include: food allergies, vitamin and microelement deficiencies, hormonal and gastrointestinal disorders (e.g., celiac disease, Crohn's disease, ulcerative colitis), some viral and bacterial infections, mechanical injuries and stress. In this paper, we presented the main etiopathogenetic factors of RAS with a special emphasis on the mechanisms of the immune response modification. Moreover, we discussed the crucial clinical symptoms and types of RAS together with epidemiologic data based on the current medical literature reports and our own observations. PMID- 24217987 TI - Dust is in the air. Part II: Effects of occupational exposure to welding fumes on lung function in a 9-year study. AB - PURPOSE: Adverse health effects of work-related contact with respirable hazardous substances are of great public interest. Because related prospective and long term follow-up studies are rare, the extent of acute and chronic pulmonary health risks of occupational exposure to welding fumes is discussed controversially in the scientific literature. The objective of the present longitudinal study during a 9-year period was to investigate the annual changes of lung function in welders. METHODS: Anthropometric measures and smoking behaviour, and spirometric tests (FVC, FEV1, and MEF50) obtained during routine occupational health checkups of female and male workers (n = 1,982) in Austria during the years 2002-2010 were analyzed. RESULTS: The study participants displayed average lung function values lower than the age- and sex-specific norm. Decrease in respiratory capacity was dependent on smoking habits and duration of occupational exposure. Specifically for welders (n = 1,326), decrease of pulmonary function was significantly associated with heavy smoking (FVC -70.7 ml, p = 0.07; FEV1 -167.4 ml, p < 0.001; MEF50 -356.2 ml/s, p < 0.001), but not with moderate smoking habits, and also with duration of occupational exposure to welding fumes per year (FVC -0.89 ml, p = 0.36; FEV1 -2.91 ml, p < 0.001; MEF50 -4.7 ml/s, p = 0.047). CONCLUSIONS: Individual smoking habits as well as duration of occupational exposure to welding fumes showed a negative impact on lung function parameters. To reduce the risk of work-associated respiratory morbidity, smoking cessation is highly recommended to personnel engaged in welding fumes- and dust-exposed occupations. PMID- 24217988 TI - Treating CTDs related fibrotic ILDs by immunosuppressants: "facts and faults". AB - Fibrotic interstitial lung diseases (ILDs) are commonly encountered in scleroderma where they significantly influence prognosis. The mainstay of treatment in idiopathic fibrotic ILDs for the past 30 years was based on the combined administration of prednisone and cyclophosphamide (CYC) or prednisone, azathioprine plus N-acetyl cysteine, recently proved ineffective and harmful. Rheumatologists also despite "facts" showing that CYC treatment has no beneficial impact on fibrotic ILDs in scleroderma continue to commit the same, in a manner of speaking, "faults" by "treating their fibrotic ILDs by immunosuppressants." In this issue of the journal, Panopoulos et al. (Lung, 191, 483-489, 2013) recognizing the minimal effect of CYC on fibrotic ILDs in scleroderma patients and the increased use in clinical practice of mycophenolate mofetil (MMF) as an alternative, report that MMF use to replace CYC in this setting is not supported, confirming that restoration of purely fibrotic damage in the lungs remains one of the most challenging fields in medicine. PMID- 24217989 TI - Cognitive ability is associated with altered medial frontal cortical circuits in the LgDel mouse model of 22q11.2DS. AB - We established a relationship between cognitive deficits and cortical circuits in the LgDel model of 22q11 Deletion Syndrome (22q11DS)-a genetic syndrome with one of the most significant risks for schizophrenia and autism. In the LgDel mouse, optimal acquisition, execution, and reversal of a visually guided discrimination task, comparable to executive function tasks in primates including humans, are compromised; however, there is significant individual variation in degree of impairment. The task relies critically on the integrity of circuits in medial anterior frontal cortical regions. Accordingly, we analyzed neuronal changes that reflect previously defined 22q11DS-related alterations of cortical development in the medial anterior frontal cortex of the behaviorally characterized LgDel mice. Interneuron placement, synapse distribution, and projection neuron frequency are altered in this region. The magnitude of one of these changes, layer 2/3 projection neuron frequency, is a robust predictor of behavioral performance: it is substantially and selectively lower in animals with the most significant behavioral deficits. These results parallel correlations of volume reduction and altered connectivity in comparable cortical regions with diminished executive function in 22q11DS patients. Apparently, 22q11 deletion alters behaviorally relevant circuits in a distinct cortical region that are essential for cognitive function. PMID- 24217990 TI - Postnatal down-regulation of the GABAA receptor gamma2 subunit in neocortical NG2 cells accompanies synaptic-to-extrasynaptic switch in the GABAergic transmission mode. AB - NG2 cells, a main pool of glial progenitors, express gamma-aminobutyric acid A (GABA(A)) receptors (GABA(A)Rs), the functional and molecular properties of which are largely unknown. We recently reported that transmission between GABAergic interneurons and NG2 cells drastically changes during development of the somatosensory cortex, switching from synaptic to extrasynaptic communication. Since synaptic and extrasynaptic GABA(A)Rs of neurons differ in their subunit composition, we hypothesize that GABA(A)Rs of NG2 cells undergo molecular changes during cortical development accompanying the switch of transmission modes. Single cell RT-PCR and the effects of zolpidem and alpha5IA on evoked GABAergic currents reveal the predominance of functional alpha1- and alpha5-containing GABA(A)Rs at interneuron-NG2 cell synapses in the second postnatal week, while the alpha5 expression declines later in development when responses are exclusively extrasynaptic. Importantly, pharmacological and molecular analyses demonstrate that gamma2, a subunit contributing to the clustering of GABA(A)Rs at postsynaptic sites in neurons, is down-regulated in NG2 cells in a cell type specific manner in concomitance with the decline of synaptic activity and the switch of transmission mode. In keeping with the synaptic nature of gamma2 in neurons, the down-regulation of this subunit is an important molecular hallmark of the change of transmission modes between interneurons and NG2 cells during development. PMID- 24217992 TI - Erratum to: A Cluster Randomized Trial of Adding Peer Specialists to Intensive Case Management Teams in the Veterans Health Administration. PMID- 24217991 TI - Neural mechanisms of object-based attention. AB - What neural mechanisms underlie the ability to attend to a complex object in the presence of competing overlapping stimuli? We evaluated whether object-based attention might involve pattern-specific feedback to early visual areas to selectively enhance the set of low-level features corresponding to the attended object. Using fMRI and multivariate pattern analysis, we found that activity patterns in early visual areas (V1-V4) are strongly biased in favor of the attended object. Activity patterns evoked by single faces and single houses reliably predicted which of the 2 overlapping stimulus types was being attended with high accuracy (80-90% correct). Superior knowledge of upright objects led to improved attentional selection in early areas. Across individual blocks, the strength of the attentional bias signal in early visual areas was highly predictive of the modulations found in high-level object areas, implying that pattern-specific attentional filtering at early sites can determine the quality of object-specific signals that reach higher level visual areas. Through computational modeling, we show how feedback of an average template to V1-like units can improve discrimination of exemplars belonging to the attended category. Our findings provide a mechanistic account of how feedback to early visual areas can contribute to the attentional selection of complex objects. PMID- 24217993 TI - Peer support: coming of age of and/or miles to go before we sleep? An introduction. PMID- 24217994 TI - A telephonic-based trial to reduce depressive symptoms among Latina breast cancer survivors. AB - OBJECTIVE: Greater mental health symptomatology of Latina breast cancer (LBC) patients along with the paucity of intervention trials to reduce distress underscores the scientific and practice gaps in comprehensive care. This trial investigated the effect of a paraprofessionally delivered, telephonic-based psycho-educational intervention on depressive symptoms among LBC patients. METHODS: Latina breast cancer patients were recruited from the California Cancer Registry, hospital registries, and support groups. Participants were randomly assigned to the intervention or control condition. The primary outcome was level of depressive symptoms as measured by the Center for Epidemiological Studies Depression scale. RESULTS: One hundred ninety-nine LBC patients (84 English language preferred and 115 Spanish language preferred) participated. The overall trial outcomes demonstrated a statistically significant decrease in depressive symptoms among LBC patients in the intervention condition compared with LBC patients in the control condition, after controlling for depressive symptoms at T1 and language (p < 0.05). At follow-up, 63% of intervention LBC patients reported at least a five-point decrease in symptoms compared with 26% of control LBC patients (p < 0.05). English language-preferred and Spanish language preferred LBC patients in the intervention condition showed approximately an eight-point mean decrease in depressive symptoms from baseline (M = 23.5 and M = 26.6, respectively) to follow-up (M = 15.7 and M = 18.4, respectively) (p < 0.001), whereas those in the control condition showed no significant change. CONCLUSIONS: Results demonstrate the effectiveness of a culturally responsive, paraprofessionally delivered intervention to reduce depressive symptoms among LBC patients. Therefore, community oncology practices can affiliate with trained paraprofessionals to implement mental health services to address distress among our growing and increasingly ethnically, linguistically, and economically diverse oncology patient population. PMID- 24217995 TI - Minimally invasive multiple lymphaticovenular anastomosis at the ankle for the prevention of lower leg lymphedema. AB - BACKGROUND: The patients with secondary unilateral lower limb lymphedema are likely to experience lymphedema of the contralateral leg in the future. Our policy is to perform preventive lymphaticovenular anastomosis (LVA) of the contralateral limb without symptoms in these patients. In this report, we describe a minimally invasive preventive LVA procedure and present the preliminary results. METHODS: Ten patients with unilateral lower leg lymphedema underwent multiple LVA procedures through a skin incision over the ankle of the contralateral limb without symptoms. The Campisi clinical stage of these limbs without symptoms was stage 0 in five cases and stage 1A in five cases. The number of anastomoses performed through the incision over the ankle was two LVAs in five cases, three LVAs in four cases, and four LVAs in one case. RESULTS: All the multiple LVAs were completed without complications. The onset of postoperative cellulitis and edematous aggravation of the limb that received the minimally invasive preventive LVA procedure was not noted in any patient during 6-month follow-up period. CONCLUSIONS: This minimally invasive preventive LVA procedure might prevent lymphedema and improve the physical appearance of the limb with minimal scarring. Long-term follow-up will be necessary to monitor the future progression of edema in these patients. PMID- 24217997 TI - Guest editorial: leukemia stem cell. PMID- 24217996 TI - Finding the target sites of RNA-binding proteins. AB - RNA-protein interactions differ from DNA-protein interactions because of the central role of RNA secondary structure. Some RNA-binding domains (RBDs) recognize their target sites mainly by their shape and geometry and others are sequence-specific but are sensitive to secondary structure context. A number of small- and large-scale experimental approaches have been developed to measure RNAs associated in vitro and in vivo with RNA-binding proteins (RBPs). Generalizing outside of the experimental conditions tested by these assays requires computational motif finding. Often RBP motif finding is done by adapting DNA motif finding methods; but modeling secondary structure context leads to better recovery of RBP-binding preferences. Genome-wide assessment of mRNA secondary structure has recently become possible, but these data must be combined with computational predictions of secondary structure before they add value in predicting in vivo binding. There are two main approaches to incorporating structural information into motif models: supplementing primary sequence motif models with preferred secondary structure contexts (e.g., MEMERIS and RNAcontext) and directly modeling secondary structure recognized by the RBP using stochastic context-free grammars (e.g., CMfinder and RNApromo). The former better reconstruct known binding preferences for sequence-specific RBPs but are not suitable for modeling RBPs that recognize shape and geometry of RNAs. Future work in RBP motif finding should incorporate interactions between multiple RBDs and multiple RBPs in binding to RNA. PMID- 24217999 TI - Acetyl-L-carnitine and prevention of chemotherapy-induced peripheral neuropathy: can anything work? PMID- 24217998 TI - Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin. AB - Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients. PMID- 24218000 TI - The global challenge of reducing breast cancer mortality. PMID- 24218001 TI - Are targeted therapies a consideration in poorly differentiated neuroendocrine tumors? PMID- 24218002 TI - In reply. PMID- 24218003 TI - Standardized approach to lymphedema screening. PMID- 24218004 TI - In reply. PMID- 24218006 TI - The basel cocktail for simultaneous phenotyping of human cytochrome P450 isoforms in plasma, saliva and dried blood spots. AB - BACKGROUND AND OBJECTIVE: Phenotyping cocktails use a combination of cytochrome P450 (CYP)-specific probe drugs to simultaneously assess the activity of different CYP isoforms. To improve the clinical applicability of CYP phenotyping, the main objectives of this study were to develop a new cocktail based on probe drugs that are widely used in clinical practice and to test whether alternative sampling methods such as collection of dried blood spots (DBS) or saliva could be used to simplify the sampling process. METHODS: In a randomized crossover study, a new combination of commercially available probe drugs (the Basel cocktail) was tested for simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Sixteen subjects received low doses of caffeine, efavirenz, losartan, omeprazole, metoprolol and midazolam in different combinations. All subjects were genotyped, and full pharmacokinetic profiles of the probe drugs and their main metabolites were determined in plasma, dried blood spots and saliva samples. RESULTS: The Basel cocktail was well tolerated, and bioequivalence tests showed no evidence of mutual interactions between the probe drugs. In plasma, single timepoint metabolic ratios at 2 h (for CYP2C19 and CYP3A4) or at 8 h (for the other isoforms) after dosing showed high correlations with corresponding area under the concentration-time curve (AUC) ratios (AUC0-24h parent/AUC0-24h metabolite) and are proposed as simple phenotyping metrics. Metabolic ratios in dried blood spots (for CYP1A2 and CYP2C19) or in saliva samples (for CYP1A2) were comparable to plasma ratios and offer the option of minimally invasive or non invasive phenotyping of these isoforms. CONCLUSIONS: This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms. PMID- 24218007 TI - Luteinizing hormone-releasing hormone agonist plus an aromatase inhibitor as second-line endocrine therapy in premenopausal females with hormone receptor positive metastatic breast cancer. AB - PURPOSE: The aim of the current study was to explore the efficacy and safety of combination therapy using a luteinizing hormone-releasing hormone (LHRH) agonist plus an aromatase inhibitor (AI) as second-line therapy in premenopausal females with hormone receptor (HR)-positive recurrent or metastatic breast cancer (MBC). METHODS: A retrospective analysis was conducted in patients registered in the breast cancer database of our institution between January 2001 and December 2012. The breast cancer database identified 14 premenopausal patients who had been treated with an LHRH agonist plus AI for HR-positive recurrent or MBC. RESULTS: Fourteen patients with recurrent breast cancer (N = 10) or metastatic disease at primary diagnosis (N = 4) were included in the present study. All patients had previously been treated with an LHRH agonist plus tamoxifen. The clinical benefit rate was 71.4% and the median TTP was 11 months (95% confidence interval 1.7-20.3 months). One patient discontinued treatment because of liver dysfunction (grade 3). CONCLUSIONS: The combination of an LHRH agonist plus an AI is a treatment option for premenopausal females with HR-positive MBC that can prolong the chemotherapy-free interval and yield effective disease stabilization. PMID- 24218008 TI - Adhesive strength of ethyl-2-cyanoacrylate tissue adhesive: how strong is it? AB - PURPOSE: We evaluated the adhesive strength of ethyl-2-cyanoacrylate and compared the findings with those of traditional monofilament synthetic sutures. We also investigated the factors that could affect the effectiveness of cyanoacrylate bonding by skin surface modifications at the adhesion site. METHODS: Using a porcine skin model, we measured the maximum load for ethyl-2-cyanoacrylate adhesive under various application conditions. RESULTS: When the application width was 5 mm, no differences were found in the maximum force load for one layer or two layers of ethyl-2-cyanoacrylate adhesive (3.3 +/- 1.7 and 4.8 +/- 1.5 N, p = 0.176). When the application width was extended to 10 mm, the maximum force load for one layer was 8.2 +/- 0.6 N, which was significantly higher than for 5 mm (p < 0.002). The force fell to within the loads generated by 6-0 to 5-0 ETHILONTM monofilament non-absorbable synthetic sutures. Roughening of the application surface had little effect on adhesion; however, smoothing resulted in a decrease in overall adhesive strength. CONCLUSIONS: The width of the application of ethyl-2-cyanoacrylate adhesive over the skin defect was important for achieving good and stable adhesive strength. Increasing the number of layers of adhesive through repeated applications of the cyanoacrylate did not increase overall adhesive strength. Skin surface modifications other than regular cleaning should be avoided. PMID- 24218009 TI - MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine. AB - MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine. PMID- 24218012 TI - Quality of life among free clinic patients associated with somatic symptoms, depression, and perceived neighborhood environment. AB - Free clinics provide free or reduced fee healthcare to individuals who lack access to primary care and are socio-economically disadvantaged. The purpose of this study is to examine health-related quality of life (HRQoL) among free clinic patients and its association with somatic symptoms, depression, and perceived neighborhood environment. Free clinic patients (n = 186) aged 18 years or older completed a self-administered survey. HRQoL, depression, somatic symptoms, and perceived neighborhood environment were measured using standardized instruments. Overall, the participants reported low level of HRQoL compared to the general healthy population. US born participants (n = 97) reported poorer psychological QoL and social relations, more somatic symptoms, and were more likely to be depressed than non-US born participants (n = 89). Higher numbers of somatic symptoms were associated with poorer environmental QoL. Depression was associated with all aspects of QoL; a higher level of depression was related to poorer QoL in all aspects. Our findings show that free clinic patients, especially US born patients, have poor HRQoL. Depression and perceived neighborhood satisfaction are key factors to determine HRQoL among free clinic patients. Mental health services and collaboration with other community organizations may help in improving HRQoL among free clinic patients. Finally, health promotion programs at the community level, not just at the clinic level, would be valuable to improve health of free clinic patients as perceived neighborhood environment is associated with their HRQoL. PMID- 24218011 TI - Transcriptional networks regulating the costamere, sarcomere, and other cytoskeletal structures in striated muscle. AB - Structural abnormalities in striated muscle have been observed in numerous transcription factor gain- and loss-of-function phenotypes in animal and cell culture model systems, indicating that transcription is important in regulating the cytoarchitecture. While most characterized cytoarchitectural defects are largely indistinguishable by histological and ultrastructural criteria, analysis of dysregulated gene expression in each mutant phenotype has yielded valuable information regarding specific structural gene programs that may be uniquely controlled by each of these transcription factors. Linking the formation and maintenance of each subcellular structure or subset of proteins within a cytoskeletal compartment to an overlapping but distinct transcription factor cohort may enable striated muscle to control cytoarchitectural function in an efficient and specific manner. Here we summarize the available evidence that connects transcription factors, those with established roles in striated muscle such as MEF2 and SRF, as well as other non-muscle transcription factors, to the regulation of a defined cytoskeletal structure. The notion that genes encoding proteins localized to the same subcellular compartment are coordinately transcriptionally regulated may prompt rationally designed approaches that target specific transcription factor pathways to correct structural defects in muscle disease. PMID- 24218013 TI - Prostaglandins before caesarean section for preventing neonatal respiratory distress. AB - BACKGROUND: Respiratory distress (RD) can occur in both preterm and term neonates born through normal vaginal delivery or caesarean section (CS). It accounts for about 30% of neonatal deaths and can occur at any time following birth. Respiratory distress syndrome (RDS), transient tachypnoea (rapid breathing) of the newborn and persistent pulmonary hypertension (increased blood pressure of pulmonary vessels) of the newborn are the most frequent clinical presentations of neonatal RD. Prostaglandins are used in routine obstetric practice to ripen the uterine cervix and to trigger labour, with those of the E series being preferred over others due to the fact that they are more uteroselective. Administration of prostaglandins to an expectant mother before delivery causes reabsorption of lung fluid from the fetal lung and promotes surfactant secretion by inducing a catecholamine surge. As a result, significant reduction in neonatal respiratory morbidity following a CS could be obtained, leading to reduced long-term complications such as bronchopulmonary dysplasia (chronic lung disease with lung tissue modification) and asthma. OBJECTIVES: The objective of this review was to determine if administration of prostaglandins before CS can improve respiratory outcomes of newborns. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We also searched three clinical trial registries; ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the WHO Clinical Trials Registry Platform (ICTRP), for ongoing studies (24 June 2013). SELECTION CRITERIA: We included all published and unpublished randomised controlled trials comparing the use of prostaglandins with other treatments (including placebo) to reduce neonatal respiratory morbidity. Participants were pregnant women with an indication for a CS, and we compared administration of prostaglandins prior to CS with no treatment, placebo or another treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and assessed trial quality, with the third review author referred to for settling any disagreements. Two review authors extracted data. Data were checked for accuracy. We used the Cochrane tool for assessing risk of bias in the included study and contacted the study authors to request additional information where appropriate. MAIN RESULTS: We found one randomised controlled trial with a low risk of bias which was carried out in a tertiary neonatal care centre in Australia. The study involved 36 women (18 received intravaginal prostaglandin E 2 gel and 18 received placebo).There was one case of neonatal respiratory distress in the control group, which the trialist reported as transient tachypnoea of the newborn (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.68, one study, n = 36).None of the neonates required mechanical ventilation and the trial authors reported median Apgar scores at one and five minutes as being similar in both groups.There were no treatment-related side effects in either group. Noradrenaline concentrations (median values (range)) were reported as being significantly higher in the cord blood samples of the intervention group compared to the control group. AUTHORS' CONCLUSIONS: Although the trial authors reported a significant increase in catecholamine levels in the intervention group, there was no significant difference in the respiratory outcomes between intervention and control groups. The quality of evidence was graded as low because the sample size was small and there were few events. No definite conclusions can thus be drawn on the effects of prostaglandins on neonatal respiratory outcomes from this review. PMID- 24218010 TI - Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration. AB - Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS. PMID- 24218014 TI - Multiple colonization of a cadaver by insects in an indoor environment: first record of Fannia trimaculata (Diptera: Fanniidae) and Peckia (Peckia) chrysostoma (Sarcophagidae) as colonizers of a human corpse. AB - We describe here a case of multiple colonization of a male cadaver found indoors in the municipality of Jaboatao dos Guararapes, Brazil. The body was colonized by six species of Diptera: Chrysomya albiceps, Chrysomya megacephala, Chrysomya putoria (Calliphoridae), Megaselia scalaris (Phoridae), Fannia trimaculata (Fanniidae), and Peckia (Peckia) chrysostoma (Sarcophagidae). The most abundant species were C. albiceps (65.0 % of all emerged adults) and C. megacephala (18.6 %). The case illustrates the ability of six insect species to simultaneously colonize a corpse in an indoor environment and represents the first collaboration between the forensic police and entomologists in Northeastern Brazil. We provide here the first record of two species, F. trimaculata and Peckia (P.) chrysostoma colonizing a human cadaver. We also report the first case of cadaver colonization by C. putoria and M. scalaris in Northeastern Brazil. Information on the development time of two species, C. albiceps and C. megacephala, were used to discuss the estimation of the post-mortem interval. Considering that the region harbors the highest rates of homicide in Brazil, implications of these findings for the consolidation of forensic entomology in the region are discussed. PMID- 24218016 TI - Perceived communication between physicians and breast cancer patients as a predicting factor of patients' health-related quality of life: a longitudinal analysis. AB - OBJECTIVE: Communication between cancer patients and healthcare providers is recognized as an important aspect of these patients' health-related quality of life (HRQOL). Nevertheless, no study has examined whether perceived communication between physicians and breast cancer patients is a determining factor in their HRQOL along the disease's trajectory. This longitudinal study aimed to ascertain whether such communication influenced the HRQOL of such women at three points in time. METHODS: The sample consisted of 120 French-speaking women with stage I or II breast cancer aged 18 years or over (mean = 55 years) who underwent a lumpectomy with adjuvant treatment. The women filled out questionnaires at three different times: around the time of diagnosis, halfway through radiotherapy and at follow-up. Either at the hospital or at home, they completed demographic and medical data questionnaires, the Medical Outcomes Study-Social Support Survey, an HRQOL questionnaire (EORTC QLQ-C30/BR23) and the Medical Communication Competence Scale. RESULTS: Generalized estimated equations analyses indicated that the women's perceptions of their own communication skills towards physicians had a greater impact on their HRQOL than the women's perception of physicians' communication skills. The women had better global health and better role, emotional, cognitive and sexual functioning as well as fewer side effects and symptoms during radiotherapy and at follow-up when they perceived themselves as competent communicators at diagnosis and during radiotherapy. CONCLUSIONS: The results underscore the importance for breast cancer patients of being proactive in information seeking and in the socio-emotional aspect of their relationship with physicians to enhance their HRQOL. PMID- 24218015 TI - Estimation of age at death based on aspartic acid racemization in elastic cartilage of the epiglottis. AB - Age estimation based on aspartic acid racemization (AAR) has been applied successfully to various tissues. For routine uses, AAR is analyzed in dentine. For cases in which teeth are unavailable, analyzing AAR in purified elastin has been shown to be an alternative method. The suitability of elastic cartilage from the epiglottis as an elastin source for age estimation based on AAR was tested. A total of 65 tissue samples (cartilage) of epiglottis and 45 samples of elastin purified from the elastic cartilage of epiglottis samples were analyzed. While the D-aspartic acid content of total tissue samples increased with age only slowly, its increase with age in purified elastin samples was similar to that in purified elastin from other tissues. The relationship between the D-aspartic acid content and age was shown to be close enough for age estimation based on AAR in purified elastin from the elastic cartilage of the epiglottis, provided a sufficient quality of elastin purification. Age estimation based on AAR in purified elastin from the epiglottis might serve as a valuable alternative in cases in which other tissues (e.g., teeth) are unavailable. PMID- 24218018 TI - Evidence-based tailoring of behavior-change campaigns: increasing fluoride-free water consumption in rural Ethiopia with persuasion. AB - Two hundred million people worldwide are at risk of developing dental and skeletal fluorosis due to excessive fluoride uptake from their water. Since medical treatment of the disease is difficult and mostly ineffective, preventing fluoride uptake is crucial. In the Ethiopian Rift Valley, a fluoride-removal community filter was installed. Despite having access to a fluoride filter, the community used the filter sparingly. During a baseline assessment, 173 face-to face interviews were conducted to identify psychological factors that influence fluoride-free water consumption. Based on the results, two behavior-change campaigns were implemented: a traditional information intervention targeting perceived vulnerability, and an evidence-based persuasion intervention regarding perceived costs. The interventions were tailored to household characteristics. The campaigns were evaluated with a survey and analyzed in terms of their effectiveness in changing behavior and targeted psychological factors. While the intervention targeting perceived vulnerability showed no desirable effects, cost persuasion decreased the perceived costs and increased the consumption of fluoride-free water. This showed that altering subjective perceptions can change behavior even without changing objective circumstances. Moreover, interventions are more effective if they are based on evidence and tailored to specific households. PMID- 24218017 TI - Epigenetics, drugs of abuse, and the retroviral promoter. AB - Drug abuse alone has been shown to cause epigenetic changes in brain tissue that have been shown to play roles in addictive behaviors. In conjunction with HIV-1 infection, it can cause epigenetic changes at the viral promoter that can result in altered gene expression, and exacerbate disease progression overall. This review entails an in-depth look at research conducted on the epigenetic effects of three of the most widely abused drugs (cannabinoids, opioids, and cocaine), with a particular focus on the mechanisms through which these drugs interact with HIV-1 infection at the viral promoter. Here we discuss the impact of this interplay on disease progression from the point of view of the nature of gene regulation at the level of chromatin accessibility, chromatin remodeling, and nucleosome repositioning. Given the importance of chromatin remodeling and DNA methylation in controlling the retroviral promoter, and the high susceptibility of the drug abusing population of individuals to HIV infection, it would be beneficial to understand the way in which the host genome is modified and regulated by drugs of abuse. PMID- 24218019 TI - Nutritional status and functional capacity of community-dwelling elderly in Southern Laos. AB - OBJECTIVES: The aim of this study was to assess the nutritional status and functional capacity of 144 community-dwelling elderly in three rural ethnic groups, namely, the Oy, the Brau and the Lao, of southern Laos. METHODS: The Mini nutritional assessment (MNA) questionnaire and Determine Your Nutritional Health checklist were used to assess nutritional status. The Barthel Activities of Daily Living questionnaire and Lawton and Brody's Instrumental Activities of Daily Living questionnaire were used to assess the functional capacity of the respondents. RESULTS: The MNA score results indicated that 92.5 % of Oy respondents, 85.4 % of Brau respondents and 60 % of Lao respondents were malnourished. Analysis of variance tests showed that the MNA scores of the Oy and Lao ethnic groups and of the Brau and Lao ethnic groups were significantly different ( both p < 0.01), but that there was no significant difference between the MNA scores of the Oy and Brau ethnic groups (p > 0.05). In terms of functional capacity, 47.2 % of Oy respondents, 43.9 % of Brau respondents and 20 % of Lao respondents had limitations in their activities of daily living, whereas 98.1 % of Oy respondents, 97.6 % of Brau respondents and 86 % of Lao respondents had limitations in their instrumental activities of daily living. Body mass index, reduced appetite, number of meals consumed daily and presence of common diseases predicted nutritional status in all three ethnic groups; the remaining factors differed by ethnicity. This result implies that ethnic differences and other factors, such as location of the village, services, resources within the village and respondents' lifestyles, can affect nutritional status. CONCLUSIONS: Because predictors of nutritional status varied by ethnicity, there is a need for area-specific interventions aimed at improving the quality of life of the elderly in these areas. PMID- 24218020 TI - Solution structure and interface-driven self-assembly of NC2, a new member of the Class II hydrophobin proteins. AB - Hydrophobins are fungal proteins that self-assemble spontaneously to form amphipathic monolayers at hydrophobic:hydrophilic interfaces. Hydrophobin assemblies facilitate fungal transitions between wet and dry environments and interactions with plant and animal hosts. NC2 is a previously uncharacterized hydrophobin from Neurospora crassa. It is a highly surface active protein and is able to form protein layers on a water:air interface that stabilize air bubbles. On a hydrophobic substrate, NC2 forms layers consisting of an ordered network of protein molecules, which dramatically decrease the water contact angle. The solution structure and dynamics of NC2 have been determined using nuclear magnetic resonance spectroscopy. The structure of this protein displays the same core fold as observed in other hydrophobin structures determined to date, including the Class II hydrophobins HFBI and HFBII from Trichoderma reesei, but certain features illuminate the structural differences between Classes I and II hydrophobins and also highlight the variations between structures of Class II hydrophobin family members. The unique properties of hydrophobins have attracted much attention for biotechnology applications. The insights obtained through determining the structure, biophysical properties and assembly characteristics of NC2 will facilitate the development of hydrophobin-based applications. PMID- 24218021 TI - Regenerative capacity of bulbar projection neurons during development: a quantitative neuronal analysis with functional correlation. AB - Critical periods and degrees of regeneration in injured olfactory bulbar projection neurons (mitral cells) were examined in adult rats whose lateral olfactory tracts (LOTs) were transected at different postnatal (P) days. After the LOTs were transected at P7, P10, and P14, a retrograde fluorescent tracer, Fluoro-Gold (FG), was injected into the posterior olfactory cortex (the olfactory tubercle and the piriform cortex), a target brain region of mitral cells, 5 weeks after the transection. FG (+) mitral cells were observed in P7 LOT-transected bulbs and some of P10 LOT-transected bulbs but not in P14 LOT-transected bulbs. Neuron numbers of regenerated FG (+) mitral cells in P2 LOT-transected adult rats decreased to approximately 70% of the normal values (actually counted number: 804+/-46; stereologically estimated number: 49 700+/-4300), and 100% of these rats were demonstrated to exhibit olfactory discriminative ability in our previous study. Meanwhile, the numbers in P7 LOT-transected adult rats further decreased to approximately 40% of the normal values, and 78% of these rats showed olfactory discriminative ability. We conclude that the critical periods of spontaneous regeneration of the LOT are between P0 and P10 and that the proportions of regenerated mitral cells decreased as rats became older. PMID- 24218022 TI - Effects of cannabinoids on tension induced by acetylcholine and choline in slow skeletal muscle fibers of the frog. AB - We investigated the effects of cannabinoids on acetylcholine (ACh) or choline contractures in slow skeletal muscle fibers from Rana pipiens. Bundles of cruralis muscle fibers were incubated with the cannabinoid receptor 1 (CB1) agonist, arachidonylcyclopropylamide (ACPA), which diminished the maximum isometric tension by 10 % and the total tension by 5 % of the ACh contracture, and 40 and 22 % of the choline contracture, respectively. Preincubation with the CB1 antagonist, AM281, or with pertussis toxin (PTX) completely blocked the effect of ACPA on the ACh contracture. On the other hand, the decrease in choline contracture by ACPA was only partially blocked by AM281 (~16 % decrease), PTX (20 %), or by dantrolene (~46 %). Our results show that ACPA modulates ACh and choline contractures, and suggest that this effect involves the participation of CB1, the ACh receptor, and -RyR in ACh contractures. For choline contractures, ACPA may also be acting through cannabinoid receptor-independent mechanisms. PMID- 24218023 TI - Alterations in the intrinsic burst activity of Purkinje neurons in offspring maternally exposed to the CB1 cannabinoid agonist WIN 55212-2. AB - Burst firing plays an important role in normal neuronal function and dysfunction. In Purkinje neurons, where the firing rate and discharge pattern encode the timing signals necessary for motor function, any alteration in firing properties, including burst activity, may affect the motor output. Therefore, we examined whether maternal exposure to the cannabinoid receptor agonist WIN 55212-2 (WIN) may affect the burst firing properties of cerebellar Purkinje cells in offspring. Whole-cell somatic patch-clamp recordings were made from cerebellar slices of adult male rats that were exposed to WIN prenatally. WIN exposure during pregnancy induced long-term alterations in the burst firing behavior of Purkinje neurons in rat offspring as evidenced by a significant increase in the mean number of spikes per burst (p < 0.05) and the prolongation of burst firing activity (p < 0.01). The postburst afterhyperpolarization potential (p < 0.001), the mean intraburst interspike intervals (p < 0.001) and the mean intraburst firing frequency (p < 0.001) were also significantly increased in the WIN-treated group. Prenatal exposure to WIN enhanced the firing irregularity as reflected by a significant decrease in the coefficient of variation of the intraburst interspike interval (p < 0.05). Furthermore, whole-cell voltage-clamp recordings revealed that prenatal WIN exposure significantly enhanced Ca(2+) channel current amplitude in offspring Purkinje neurons compared to control cells. Overall, the data presented here strongly suggest that maternal exposure to cannabinoids can induce long-term changes in complex spike burst activity, which in turn may lead to alterations in neuronal output. PMID- 24218024 TI - Fascin and cyclin D1 immunoreactivity in non-neoplastic vulvar squamous epithelium, vulvar intraepithelial neoplasia and invasive squamous carcinoma: correlation with Ki67 and p16 protein expression. AB - AIMS: To investigate cyclin D1 and fascin immunoreactivity in normal, reactive and neoplastic vulvar skin correlating the findings with p16 protein and Ki67 expression. METHODS: 66 vulvar biopsy or resection specimens demonstrating normal appearances, reactive epidermal changes, usual-type vulvar intraepithelial neoplasia (uVIN), differentiated-type VIN (dVIN), p16-positive squamous cell carcinoma (SCC) and p16-negative SCC were examined immunohistochemically for cyclin D1, fascin, Ki67 and p16 protein. Where applicable, expression patterns were compared in microanatomically distinct areas, particularly at the invasive front (deep tumour margin) of SCC. RESULTS: Normal epidermis showed parabasal Ki67 and cyclin D1 staining while fascin labelled cells in the lower one-third of the epithelium. Reactive and dVIN specimens demonstrated mildly increased Ki67 and cyclin D1 expression that maintained parabasal polarity, whereas uVIN and p16 positive SCC were characterised by loss of cyclin D1 staining. However, in 14 of 20 p16-positive SCC small infiltrative tumour groups and single infiltrating cells at the invasive front showed a cyclin D1-positive/ Ki67-negative phenotype. In contrast, p16-negative SCC generally showed diffuse and concordant cyclin D1 and Ki67 labelling, including at the invasive margin. Fascin expression was increased in all VIN and SCC lesions. CONCLUSIONS: Variations in cyclin D1 and Ki67 expression between p16-positive and p16-negative vulvar SCCs suggest different mechanisms of invasion in these tumour subgroups. Fascin is upregulated in vulvar squamous neoplasia but immunostaining does not discriminate in situ from invasive lesions nor putative human papilloma virus (HPV)-associated and HPV independent SCCs. PMID- 24218025 TI - Sentinel lymph nodes with isolated tumour cells and micrometastases in breast cancer: clinical relevance and prognostic significance. AB - AIM: We performed a retrospective review to determine the prognostic significance of isolated tumour cells (ITCs) and micrometastases to the sentinel lymph nodes of patients with breast cancer. METHODS: A total of 1044 patients with a diagnosis of invasive carcinoma of the breast who underwent surgical treatment including the sentinel lymph node biopsy procedure from July 2004 to October 2009 were included in the study. RESULTS: In 710 (68%) patients, no metastasis was seen to the sentinel lymph nodes. ITCs were detected in 22 (2.1%) patients, micrometastasis in 52 (5.0%) and macrometastases in 260 (24.9%). With a median follow-up of 28.8 months, disease recurrence was seen in 38 (3.6%) patients and 15 (1.5%) patients died of disease. No disease recurrence or deaths were recorded in women with ITCs in sentinel lymph nodes. In the micrometastasis group, 2 patients suffered disease recurrence and both died of disease. CONCLUSIONS: We conclude that ITCs in the sentinel lymph nodes did not adversely impact disease free and overall survivals. Although only 2 recurrences with subsequent death occurred in the micrometastasis group, it may suggest a propensity for presence of micrometastases to augur a worse outcome, and justifies continued segregation of ITCs from micrometastasis. PMID- 24218026 TI - Epstein-Barr virus is rarely associated with diffuse large B cell lymphoma in Taiwan and carries a trend for a shorter median survival time. AB - AIMS: Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is characterised by frequent extranodal involvement, a morphological spectrum from polymorphous to monomorphous and a poor prognosis. The frequency is higher in Japan and Korea but lower in the West, while the status in Taiwan has not been reported yet. METHODS: We conducted a retrospective study of DLBCL in a single institute in Taiwan by immunohistochemistry and in situ hybridisation for EBV. RESULTS: Of the 424 consecutive DLBCL cases, 332 cases were studied for EBV. 15 (4.5%) were EBV-positive and 13 (3.9%) fulfil WHO criteria of EBV-positive DLBCL of the elderly with a median age of 75. Of these 15 cases, extranodal presentation occurred in 11 (73%) patients with predominance in the gastrointestinal tract and 6 (40%) were of germinal centre B cell phenotype. There was no difference between EBV-positive and -negative patients in terms of age, gender, nodal versus extranodal presentation, and immunophenotypical profile. EBV-positive patients showed a trend for a shorter median survival time (5.0 vs 39.3 months; p=0.058). Of all DLBCL patients, multivariable analysis revealed a significantly worse overall survival for patients older than 50 (p=0.001) and for those with bcl-6-negative tumours (p=0.003) but not with other clinicopathological factors including EBV status. CONCLUSIONS: EBV-positive DLBCL of the elderly is relatively rare in Taiwan, with an incidence intermediate between Japan/Korea and the West. Further studies are warranted to clarify the association of EBV and the clinicopathological features and the prognostic significance in patients with DLBCL. PMID- 24218027 TI - Male hypercalciuric stone formers with low renal calcium reabsorption. AB - AIMS: Hypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors. METHODS: A retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium. RESULTS: 276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175-371 and 153-316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative. CONCLUSIONS: Hypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier. PMID- 24218028 TI - Association of HER1 amplification with poor prognosis in well differentiated gastric carcinomas. AB - AIMS: The pattern of E-cadherin expression and the HER1/HER2 status were studied in European patients with gastric carcinomas in relation with their differentiation and prognosis. METHODS: 82 gastric carcinomas (five papillary, 52 tubular, 19 poorly cohesive and six mixed according to WHO classification) were investigated for E-cadherin distribution (normal: restricted to the membrane; abnormal: absent or cytoplasmic expression), HER1 and HER2 expression using HercepTest and amplification using fluorescent in situ hybridisation. Statistical analysis assessed the association between the markers and their correlation with clinicopathological parameters and follow-up information. RESULTS: Abnormal E cadherin distribution was found in 34 of the 82 gastric carcinomas (41%) (18/25 poorly cohesive or mixed (72%); 16/57 papillary or tubular type (28%)). HER1 overexpression (3+) and equivocal expression (2+) were found in five carcinomas (6%; four tubular and one poorly cohesive) and eight carcinomas (10%; six tubular and two poorly cohesive), respectively. HER2 overexpression (3+) and equivocal expression (2+) were found in seven carcinomas (8%; five papillary and two tubular) and three carcinomas (4%; three tubular), respectively. Amplification of HER1 or HER2 was detected in 14 gastric carcinomas (five papillary and nine tubular). All of them showed a normal E-cadherin distribution. In the univariate analysis, only HER1 amplification had a prognostic impact, while HER2 amplification and E-cadherin expression/distribution were not per se prognostically relevant. CONCLUSIONS: E-cadherin immunostaining and HER1 in situ hybridisation define a group of well differentiated gastric carcinomas with poor prognosis eligible for an aggressive therapeutic approach. PMID- 24218029 TI - Association of systemic characteristics and histological variations in a case study of adult-onset asthma and periocular xanthogranuloma. PMID- 24218031 TI - Ambient fine particulate matter, nitrogen dioxide, and term birth weight in New York, New York. AB - Building on a unique exposure assessment project in New York, New York, we examined the relationship of particulate matter with aerodynamic diameter less than 2.5 MUm and nitrogen dioxide with birth weight, restricting the population to term births to nonsmokers, along with other restrictions, to isolate the potential impact of air pollution on growth. We included 252,967 births in 2008 2010 identified in vital records, and we assigned exposure at the residential location by using validated models that accounted for spatial and temporal factors. Estimates of association were adjusted for individual and contextual sociodemographic characteristics and season, using linear mixed models to quantify the predicted change in birth weight in grams related to increasing pollution levels. Adjusted estimates for particulate matter with aerodynamic diameter less than 2.5 MUm indicated that for each 10-ug/m(3) increase in exposure, birth weights declined by 18.4, 10.5, 29.7, and 48.4 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. Adjusted estimates for nitrogen dioxide indicated that for each 10 ppb increase in exposure, birth weights declined by 14.2, 15.9, 18.0, and 18.0 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. These results strongly support the association of urban air pollution exposure with reduced fetal growth. PMID- 24218032 TI - Deviance detection based on regularity encoding along the auditory hierarchy: electrophysiological evidence in humans. AB - Detection of changes in the acoustic environment is critical for survival, as it prevents missing potentially relevant events outside the focus of attention. In humans, deviance detection based on acoustic regularity encoding has been associated with a brain response derived from the human EEG, the mismatch negativity (MMN) auditory evoked potential, peaking at about 100-200 ms from deviance onset. By its long latency and cerebral generators, the cortical nature of both the processes of regularity encoding and deviance detection has been assumed. Yet, intracellular, extracellular, single-unit and local-field potential recordings in rats and cats have shown much earlier (circa 20-30 ms) and hierarchically lower (primary auditory cortex, medial geniculate body, inferior colliculus) deviance-related responses. Here, we review the recent evidence obtained with the complex auditory brainstem response (cABR), the middle latency response (MLR) and magnetoencephalography (MEG) demonstrating that human auditory deviance detection based on regularity encoding-rather than on refractoriness occurs at latencies and in neural networks comparable to those revealed in animals. Specifically, encoding of simple acoustic-feature regularities and detection of corresponding deviance, such as an infrequent change in frequency or location, occur in the latency range of the MLR, in separate auditory cortical regions from those generating the MMN, and even at the level of human auditory brainstem. In contrast, violations of more complex regularities, such as those defined by the alternation of two different tones or by feature conjunctions (i.e., frequency and location) fail to elicit MLR correlates but elicit sizable MMNs. Altogether, these findings support the emerging view that deviance detection is a basic principle of the functional organization of the auditory system, and that regularity encoding and deviance detection is organized in ascending levels of complexity along the auditory pathway expanding from the brainstem up to higher-order areas of the cerebral cortex. PMID- 24218030 TI - Replication of breast cancer susceptibility loci in whites and African Americans using a Bayesian approach. AB - Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993-2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer-related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations. PMID- 24218033 TI - Community-acquired respiratory viruses after lung transplantation: common, sometimes silent, potentially lethal. PMID- 24218034 TI - Trends in sickness certification of injured workers by general practitioners in Victoria, Australia. AB - BACKGROUND: General practitioners (GPs) play a critical role in facilitating injured workers return to work via their ability to certify capacity to return to employment. However, little is known about the sickness certification patterns of GPs in the context of workers' compensation claims. AIM: To determine if GPs' sickness certification behaviour has changed between 2003 and 2010 in Victoria, Australia. METHOD: Retrospective population-based cohort study of all injured workers with an accepted compensation claim. Sickness certification rates per 1,000 working population per annum were calculated. General regression models adjusted for workers' age and annual claim number were fitted to summarize changes in count and duration (expressed as incidence rate ratios or IRRs) of unfit for work (UFW) versus alternate duties (ALT) certificates within six categories of work-related injury and disease. RESULTS: 92,134 UFW and 28,293 ALT certificates were identified. A significant decrease in the unadjusted annual certification rates per 1,000 working population was observed. However, after adjusting for the annual number of claims and age, the IRRs of certificates increased over time. The rate of injuries and IRRs of certificates varied across affliction categories, IRRs being higher in mental health conditions in women than in men (IRR: 0.40, 95 % CI 0.38-0.41 vs. IRR: 0.17, 95 % CI 0.16-0.18). The duration of certificates remained stable, with the ALT being longer than UFW certificates in all claimants. CONCLUSION: Our findings indicate that GPs in Victoria issue an increasing number of UFW sickness certificates each year. Further research is required to investigate the reasons for such practises. PMID- 24218035 TI - Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial. AB - We have carried out a stratified phase II study of sorafenib (So) in patients with advanced angiosarcoma (n = 32) and epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic biomarkers. Using the ELISA method (R&D Systems), circulating biomarkers (VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter), stem cell factor (SCF, in picograms per milliliter), placental growth factor (PlGF, in picograms per milliliter), VEGF-C (in picograms per milliliter), and E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days. VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF, VEGF-C, and E-selectin. Only two biomarkers were associated with better outcome as follows: VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of VEGF-A and time to progression (TTP) (r = -0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and TTP. Low level of VEGF-A at baseline (<500) was significantly associated with better outcome. PMID- 24218037 TI - Association between left ventricular dysfunction, anemia, and chronic renal failure. Analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) cohort. AB - BACKGROUND: Anemia and chronic renal failure (CRF) are frequent comorbidities in patients with heart failure (HF), and they have been reported to be associated with increased mortality and hospitalization rates. HF, anemia, and CRF have been reported to interact with each other forming a vicious cycle termed cardio-renal anemia syndrome. The aim of the present study was to evaluate the association of HF, anemia, and CRF using data from the large-scale"Heart Failure Prevalence and Predictors in Turkey (HAPPY)" study. PATIENTS AND METHODS: Among the HAPPY cohort, 3,369 subjects who had either left ventricular dysfunction (LVD) or normal left ventricular function on echocardiography or normal serum NT-proBNP levels were included in this analysis. RESULTS: The prevalence of anemia and CRF was significantly higher in patients with LVD compared with subjects with normal ventricular function (20.7 % vs. 4.0 % and 19.0 % vs. 3.7 %, respectively; p < 0.001 for each). Binary logistic regression analyses for the presence of LVD, anemia, and CRF demonstrated that each one was an independent predictor for the presence of the others. CONCLUSION: These findings point to the presence of cardio-renal-anemia syndrome and the necessity of treating these comorbidities in patients with HF. PMID- 24218036 TI - Analysis of heat-labile sites generated by reactions of depleted uranium and ascorbate in plasmid DNA. AB - The goal of this study was to characterize how depleted uranium (DU) causes DNA damage. Procedures were developed to assess the ability of organic and inorganic DNA adducts to convert to single-strand breaks (SSB) in pBR322 plasmid DNA in the presence of heat or piperidine. DNA adducts formed by methyl methanesulfonate, cisplatin, and chromic chloride were compared with those formed by reaction of uranyl acetate and ascorbate. Uranyl ion in the presence of ascorbate produced U DNA adducts that converted to SSB on heating. Piperidine, which acted on DNA methylated by methyl methanesulfonate to convert methyl-DNA adducts to SSB, served in the opposite fashion as U-DNA adducts by decreasing the level of SSB. The observation that piperidine also decreased the gel shift for metal-DNA adducts formed by monofunctional cisplatin and chromic chloride was interpreted to suggest that piperidine served to remove U-DNA adducts. Radical scavengers did not affect the formation of uranium-induced SSB, suggesting that SSB arose from the presence of U-DNA adducts and not from the presence of free radicals. A model is proposed to predict how U-DNA adducts may serve as initial lesions that convert to SSB or AP sites. The results suggest that DU can act as a chemical genotoxin that does not require radiation for its mode of action. Characterizing the DNA lesions formed by DU is necessary to assess the relative importance of different DNA lesions in the formation of DU-induced mutations. Understanding the mechanisms of formation of DU-induced mutations may contribute to identification of biomarkers of DU exposure in humans. PMID- 24218038 TI - Futility rules in bioequivalence trials with sequential designs. AB - Health Canada, the US Food and Drug Administration, as well as the European Medicines Agency consider sequential designs acceptable for bioequivalence studies as long as the type I error is controlled at 5%. The EU guideline explicitly asks for specification of stopping rules, so the goal of this work is to investigate how stopping rules may affect type I errors and power for recently published sequential bioequivalence trial designs. Using extensive trial simulations, five different futility rules were evaluated for their effect on type I error rates and power in two-stage scenarios. Under some circumstances, notably low sample size in stage 1 and/or high variability power may be very severely affected by the stopping rules, whereas type I error rates appear less affected. Because applicants may initiate sequential studies when the variability is not known in advance, achieving sufficient power and thereby complying with certain guideline requirements may be challenging and application of optimistic futility rules could possibly be unethical. This is the first work to investigate how futility rules affect type I errors and power in sequential bioequivalence trials. PMID- 24218040 TI - Relative peripheral defocus and myopic progression in children. PMID- 24218039 TI - Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, post-LASIK or PRK, and keratoconic or keratoconus-suspect eyes. AB - BACKGROUND: The aim of this meta-analysis is to evaluate the central corneal thickness (CCT) measurement differences between Pentacam (Oculus Inc., Germany) and Ultrasound Pachymetry (USP) in normal (unoperated eyes , myopic and astigmatic eyes without corneal disease or topographic irregularity), after laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), and keratoconic or keratoconus suspected eyes. We assess whether Pentacam and USP have similar CCT differences in normal, thinner corneas after LASIK or PRK procedures, and kerotoconic or keratoconus suspected eyes. METHODS: Data sources, including PubMed, Medline, EMBASE, and Cochrane Central Registry of Controlled Trials on the Cochrane Library, were searched to find the relevant studies. Primary outcome measures were CCT measurement between Pentacam and USP. Three groups of eyes were analyzed: normal; LASIK or PRK eyes; and keratoconus suspected or keratoconic eyes. RESULTS: Nineteen studies describing 1,908 eyes were enrolled in the normal group. Pentacam results were 1.47 MUm ,95 % confidence interval (CI) -2.32 to 5.27, higher than USP without statistically significant difference (P = 0.45). Nine studies with total 539 eyes were included in the corneas after LASIK or PRK. The mean difference in the CCT measurement with Pentacam and ultrasound pachymetry was 1.03 MUm, with the 95 % CI -3.36 to 5.42, there was no statistically difference (P = 0.64). Four studies with a total of 185 eyes were included in the keratoconic eyes or keratoconus-suspect group, however,the mean difference was -6.33 MUm (95 % CI -9.17 to-3.49), which was statistically different between Pentacam and ultrasound pachymetry in the CCT measurement (P < 0.0001). CONCLUSIONS: Pentacam offers similar CCT results to ultrasound pachymetry in normal eyes, thinner corneas after LASIK or PRK procedures. However, in keratoconic or keratoconus-suspect eyes, Pentacam slightly underestimates the central corneal thickness than does ultrasound pachymetry, which may result from the difficulty in fixation of keratoconic eyes, misalignment of Pentacam and the variation of ultrasonic velocity due to the histological deformation. PMID- 24218041 TI - Increased intravitreal angiopoietin-2 levels associated with rhegmatogenous retinal detachment. AB - PURPOSE: To explore factors related to pathogenesis of rhegmatogenous retinal detachment (RRD) and development of proliferative vitreoretinopathy (PVR), vitreous levels of angiopoietin-1 and -2 (Ang-1 and -2), previously undefined in RRD, transforming growth factor-(TGF) beta1, vascular endothelial growth factor (VEGF), erythropoietin (EPO) and proteolytic mediators of extracellular matrix remodelling (MMP-2 and -9) were compared in eyes with RRD and eyes with idiopathic macular hole or pucker. METHODS: Vitreous samples were collected from 117 eyes with RRD (study group) and 40 eyes with macular hole or pucker (control group). Growth factors were measured by ELISA and matrix metalloproteinases (MMPs) by gelatin zymography. RESULTS: The mean vitreous concentrations of Ang-2, MMP-2, and MMP-9 were higher (all p < 0.01), whereas concentration of VEGF was lower (p = 0.01) in eyes with RRD relative to controls. Logistic regression analysis identified Ang-2 concentration as a novel marker of RRD (p = 0.0001, OR 48.7). Ang-1, EPO, and total TGF-beta1 levels were not significantly different between the groups. However, TGF-beta1 and MMP-2 were increased in eyes with total RRD compared to those with local RRD (p <= 0.05). In eyes with PVR, no differences were observed in any studied marker as compared with non-PVR eyes. CONCLUSIONS: Current results reveal Ang-2 as a key factor upregulated in RRD. It may co-operate with fibrosis-associated factors and contribute to vascular complications such as breakdown of blood-eye barrier and PVR development. PMID- 24218042 TI - Pars plana vitrectomy for treatment of advanced Coats' disease--presentation of a modified surgical technique and long-term follow-up. AB - BACKGROUND: To present a modified surgical technique in the treatment of retinal detachment secondary to advanced Coats' disease in children, and report on long term anatomical and functional outcome. METHODS: We analysed an interventional case series of 13 patients (13 eyes) with advanced Coats' disease characterised by retinal detachment in addition to massive subretinal exudates and vascular malformation. The presented patients underwent pars plana vitrectomy (PPV), including a modified technique of exocryotherapy applied after fluid-air exchange in order to achieve complete treatment of the vascular changes, to reduce associated side-effects, and to avoid retinectomy and silicone oil tamponade. RESULTS: Within a median follow-up period of 37 months (range: 18-66 months), no enucleation was necessary. Four eyes (31 %) did not need any further therapy, and in nine eyes (69 %) additional treatments were performed. Six patients (46 %) required revisional surgery with silicone oil tamponade. In ten eyes (77 %), the pathologic vessels and exudates finally regressed and the retina reattached. Visual acuity (VA) could be stabilized in the majority of patients: in three eyes (27 %) VA improved, in four eyes (36 %) VA remained stable, in four eyes (36 %) visual acuity (VA) deteriorated, and in two eyes VA could not be evaluated. CONCLUSIONS: The presented modified technique allows for sufficient cryotherapy of vascular malformations, even in the presence of massive exudation, in a subset of patients with advanced Coats' disease, and thus may reduce surgery-related complications and improve the rehabilitation process of these young patients. PMID- 24218043 TI - Role of interleukin-1beta in hypoxia-induced depression of glutamate uptake in retinal Muller cells. AB - BACKGROUND: It is suggested that hypoxic-ischemic retinal diseases induce loss of retinal ganglion cells. Excess glutamate release is involved in these conditions. A predominant function of Muller cells is to regulate glutamate levels, but in these diseases the function is compromised. The present study was performed to investigate the role of interleukin-1beta(IL-1beta)on the glutamate uptake in retinal Muller cells under hypoxia and to study the possible mechanism. METHODS: The levels of IL-1beta,Kir4.1, and GLAST in retinal Muller cells under hypoxia were analyzed by Western blotting and realtime-RT-PCR, and glutamate uptake assay was undertaken to investigate the activity of GLAST. After being treated with IL 1betaunder normoxia, these proteins (Kir4.1 and GLAST) and their mRNAs, and glutamate uptake activity in Muller cells were investigated. To confirm the effect of IL-1betaon glutamate uptake activity in Muller cells, addition of IL 1ra was used. RESULTS: Under hypoxia, Muller cells glutamate uptake, Kir4.1 and GLAST expressions were decreased significantly; however, IL-1betaexpression was increased. IL-1betatreatment induced depression of glutamate uptake, decrease of Kir4.1 and GLAST expressions in retinal Muller cells under normoxia. Moreover, addition of IL-1ra significantly ameliorated decreases in Kir4.1 and GLAST expressions, and compromise of glutamate uptake activity in retinal Muller cells under hypoxia. CONCLUSIONS: These findings indicated that decreases in Kir4.1 and GLAST expressions and depression of glutamate uptake in retinal Muller cells under hypoxia may be induced by the inflammatory cytokine IL-1beta. PMID- 24218044 TI - Piwi regulates Vasa accumulation during embryogenesis in the sea urchin. AB - BACKGROUND: Piwi proteins are essential for germ line development, stem cell maintenance, and more recently found to function in epigenetic and somatic gene regulation. In the sea urchin Strongylocentrotus purpuratus, two Piwi proteins, Seawi and Piwi-like1, have been identified, yet their functional contributions have not been reported. RESULTS: Here we found that Seawi protein was localized uniformly in the early embryo and then became enriched in the primordial germ cells (PGCs) (the small micromere lineage) from blastula stage and thereafter. Morpholino knockdown of Sp-seawi diminished PGC-specific localization of Seawi proteins, and altered expression of other germ line markers such as Vasa and Gustavus, but had no effect on Nanos. Furthermore, Seawi knockdown transiently resulted in Vasa positive cell proliferation in the right coelomic pouch that appear to be derived from the small micromere lineage, yet they quickly disappeared with an indication of apoptosis by larval stage. Severe Seawi knockdown resulted in an increased number of apoptotic cells in the entire gut area. CONCLUSION: Piwi proteins appear to regulate PGC proliferation perhaps through control of Vasa accumulation. In this organism, Piwi is likely regulating mRNAs, not just transposons, and is potentially functioning both inside and outside of the germ line during embryogenesis. PMID- 24218045 TI - Computerized advice on drug dosage to improve prescribing practice. AB - BACKGROUND: Maintaining therapeutic concentrations of drugs with a narrow therapeutic window is a complex task. Several computer systems have been designed to help doctors determine optimum drug dosage. Significant improvements in health care could be achieved if computer advice improved health outcomes and could be implemented in routine practice in a cost-effective fashion. This is an updated version of an earlier Cochrane systematic review, first published in 2001 and updated in 2008. OBJECTIVES: To assess whether computerized advice on drug dosage has beneficial effects on patient outcomes compared with routine care (empiric dosing without computer assistance). SEARCH METHODS: The following databases were searched from 1996 to January 2012: EPOC Group Specialized Register, Reference Manager; Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Ovid; EMBASE, Ovid; and CINAHL, EbscoHost. A "top up" search was conducted for the period January 2012 to January 2013; these results were screened by the authors and potentially relevant studies are listed in Studies Awaiting Classification. The review authors also searched reference lists of relevant studies and related reviews. SELECTION CRITERIA: We included randomized controlled trials, non randomized controlled trials, controlled before-and-after studies and interrupted time series analyses of computerized advice on drug dosage. The participants were healthcare professionals responsible for patient care. The outcomes were any objectively measured change in the health of patients resulting from computerized advice (such as therapeutic drug control, clinical improvement, adverse reactions). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality. We grouped the results from the included studies by drug used and the effect aimed at for aminoglycoside antibiotics, amitriptyline, anaesthetics, insulin, anticoagulants, ovarian stimulation, anti-rejection drugs and theophylline. We combined the effect sizes to give an overall effect for each subgroup of studies, using a random-effects model. We further grouped studies by type of outcome when appropriate (i.e. no evidence of heterogeneity). MAIN RESULTS: Forty-six comparisons (from 42 trials) were included (as compared with 26 comparisons in the last update) including a wide range of drugs in inpatient and outpatient settings. All were randomized controlled trials except two studies. Interventions usually targeted doctors, although some studies attempted to influence prescriptions by pharmacists and nurses. Drugs evaluated were anticoagulants, insulin, aminoglycoside antibiotics, theophylline, anti-rejection drugs, anaesthetic agents, antidepressants and gonadotropins. Although all studies used reliable outcome measures, their quality was generally low.This update found similar results to the previous update and managed to identify specific therapeutic areas where the computerized advice on drug dosage was beneficial compared with routine care:1. it increased target peak serum concentrations (standardized mean difference (SMD) 0.79, 95% CI 0.46 to 1.13) and the proportion of people with plasma drug concentrations within the therapeutic range after two days (pooled risk ratio (RR) 4.44, 95% CI 1.94 to 10.13) for aminoglycoside antibiotics;2. it led to a physiological parameter more often within the desired range for oral anticoagulants (SMD for percentage of time spent in target international normalized ratio +0.19, 95% CI 0.06 to 0.33) and insulin (SMD for percentage of time in target glucose range: +1.27, 95% CI 0.56 to 1.98);3. it decreased the time to achieve stabilization for oral anticoagulants (SMD -0.56, 95% CI -1.07 to -0.04);4. it decreased the thromboembolism events (rate ratio 0.68, 95% CI 0.49 to 0.94) and tended to decrease bleeding events for anticoagulants although the difference was not significant (rate ratio 0.81, 95% CI 0.60 to 1.08). It tended to decrease unwanted effects for aminoglycoside antibiotics (nephrotoxicity: RR 0.67, 95% CI 0.42 to 1.06) and anti-rejection drugs (cytomegalovirus infections: RR 0.90, 95% CI 0.58 to 1.40);5. it tended to reduce the length of time spent in the hospital although the difference was not significant (SMD -0.15, 95% CI -0.33 to 0.02) and to achieve comparable or better cost-effectiveness ratios than usual care;6. there was no evidence of differences in mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants.For all outcomes, statistical heterogeneity quantified by I(2) statistics was moderate to high. AUTHORS' CONCLUSIONS: This review update suggests that computerized advice for drug dosage has some benefits: it increases the serum concentrations for aminoglycoside antibiotics and improves the proportion of people for which the plasma drug is within the therapeutic range for aminoglycoside antibiotics.It leads to a physiological parameter more often within the desired range for oral anticoagulants and insulin. It decreases the time to achieve stabilization for oral anticoagulants. It tends to decrease unwanted effects for aminoglycoside antibiotics and anti-rejection drugs, and it significantly decreases thromboembolism events for anticoagulants. It tends to reduce the length of hospital stay compared with routine care while comparable or better cost-effectiveness ratios were achieved.However, there was no evidence that decision support had an effect on mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimize the effect of computerized advice.Taking into account the high risk of bias of, and high heterogeneity between, studies, these results must be interpreted with caution. PMID- 24218046 TI - Synthesis, characterization, and antimicrobial activity of silver(I) and copper(II) complexes of phosphate derivatives of pyridine and benzimidazole. AB - Two silver(I) complexes--[Ag(4-pmOpe)]NO3}(n) and [Ag(2-bimOpe)2]NO3--and three copper(II) complexes--[Cu4Cl6O(2-bimOpe)4], [CuCl2(4-pmOpe)2], and [CuCl2(2 bis(pm)Ope]--were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe), 1H-benzimidazol-2-ylmethyl diethyl phosphate (2-bimOpe), and ethyl bis(pyridin-2-ylmethyl)phosphate (2-bis(pm)Ope). These compounds were characterized by 1H, 13C, and 31P NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4-pmOpe)]NO3}n and [Cu4Cl6O(2-bimOpe)4] were determined by single-crystal X-ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ~19 MUM). [Ag(2-bimOpe)2]NO3 was particularly active against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus epidermidis, with MIC values of ~5 and ~10 MUM, respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500 MUg mL-1. PMID- 24218047 TI - Hierarchical spatio-temporal mapping of premature mortality due to alcoholic liver disease in Hungary, 2005-2010. AB - BACKGROUND: Excess alcohol consumption is a major public health issue in Hungary, with high mortality rates from alcohol disease. In addition, excess alcohol consumption has been found to differ by socioeconomic and environmental factors. METHODS: The spatial pattern of mortality from alcoholic liver disease across Hungary for the period 2005 and 2010, at municipality level, was investigated by sex using Bayesian modelling. The changes in mortality over this 6-year period were analysed using hierarchical spatio-temporal disease mapping. The association between the spatial distribution of mortality from alcoholic liver disease and cirrhosis and deprivation (by sex) was also assessed using a Hungarian-specific deprivation index. RESULTS: A statistically significant association was found between mortality and deprivation status in males. Areas of significantly highest age-adjusted relative risks were found, for males, in the south-western part, and at the eastern border of the country. A number of areas showed area-specific trends that were significantly steeper than the national average mortality trend. CONCLUSION: Using our findings, population groups with increasing mortality trends were identified, which may help decision makers fund effective health promotion programmes to reduce mortality rates in the working-age population. PMID- 24218048 TI - The effect of naltrexone on body fat mass in olanzapine-treated schizophrenic or schizoaffective patients: a randomized double-blind placebo-controlled pilot study. AB - Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effects of opioid blockade on OLZ-treated patients' metabolic status. Patients with schizophrenia or schizoaffective disorder (n=30) on a stable dose of OLZ were randomized in a double-blind fashion to receive an opioid receptor antagonist, naltrexone (NTX), (n=14) or placebo (n=16). The primary outcome measure was the change in body mass index (BMI) at 12 weeks. Secondary measures included body fat and fat-free mass, along with homeostasis model assessment-estimated insulin resistance (HOMA-IR), plasma lipids and liver function tests (LFTs). There was no significant change in BMI between the treatment arms. However, in comparison to the OLZ + placebo combination, the OLZ + NTX group displayed a significant decrease in the fat and increase in fat-free mass along with a trend towards improvement in HOMA-IR values. There were no significant differences in plasma lipids and LFTs. These findings suggest that addition of NTX to OLZ may attenuate OLZ-induced body fat mass gain. A larger study of longer duration will be needed to confirm these results. PMID- 24218049 TI - Solution NMR analysis of the interaction between the actinoporin sticholysin I and DHPC micelles--correlation with backbone dynamics. AB - Sticholysin I (StI), an actinoporin expressed as a water-soluble protein by the sea anemone Stichodactyla helianthus, binds to natural and model membranes, forming oligomeric pores. It is proposed that the first event of a multistep pore formation mechanism consists of the monomeric protein attachment to the lipid bilayer. To date there is no high-resolution structure of the actinoporin pore or other membrane-bound form available. Here we evaluated StI:micelle complexes of variable lipid composition to look for a suitable model for NMR studies. Micelles of pure or mixed lysophospholipids and of dihexanoyl phosphatidylcholine (DHPC) were examined. The StI:DHPC micelle was found to be the best system, yielding a stable sample and good quality spectra. A comprehensive chemical shift perturbation analysis was performed to map the StI membrane recognition site in the presence of DHPC micelles. The region mapped (residues F(51), R(52), S(53) in loop 3; F(107), D(108), Y(109), W(111), Y(112), W(115) in loop 7; Q(129), Y(132), D(134), M(135), Y(136), Y(137), G(138) in helix-alpha2) is in agreement with previously reported data, but additional residues were found to interact, especially residues V(81), A(82), T(83), G(84) in loop 5, and A(85), A(87) in strand-beta5. Backbone dynamics measurements of StI free in solution and bound to micelles highlighted the relevance of protein flexibility for membrane binding and suggested that a conformer selection process may take place during protein membrane interaction. We conclude that the StI:DHPC micelles system is a suitable model for further characterization of an actinoporin membrane-bound form by solution NMR. PMID- 24218050 TI - Use of the metastatic breast cancer progression (MBC-P) questionnaire to assess the value of progression-free survival for women with metastatic breast cancer. AB - While overall survival (OS) has historically been the primary endpoint for clinical trials in oncology, progression-free survival (PFS) has gained acceptance as a valuable surrogate endpoint. However, there are no known published reports about the value of PFS from the patient's perspective. We developed a questionnaire that included items regarding quality of life (QoL) and the importance of different treatment outcomes and presented hypothetical scenarios for which respondents were asked to indicate their preferences concerning treatments as they relate to PFS. 282 women with metastatic breast cancer (MBC), ranging in age from 21 to 80 years completed an online version of this questionnaire. The majority of women (66 %) had been diagnosed with MBC within the previous 3 years and 56 % had been told their MBC had progressed. When asked to rank five treatment characteristics from most important to least important, respondents ranked "extending PFS" as the second most important treatment outcome after OS. When presented with a hypothetical scenario of two women receiving different treatments, respondents preferred the treatment that resulted in longer PFS (16 vs. 12 months), even when OS and side effects were assumed to be equal. Specifically, when asked to consider which woman within the hypothetical scenario had better QoL, physical functioning, and emotional well being, respondents more often chose the woman who experienced longer PFS (QoL: 40 vs. 6 %; physical functioning: 32 vs. 8 %; emotional well-being: 58 vs. 6 %) compared to the woman within the hypothetical scenario who had a shorter time of progression. Respondents rated their own QoL highest after being told their MBC was responding to treatment (mean score 76.6) versus after the initial diagnosis of breast cancer and MBC (68.5 and 60.3). These findings suggest that extending PFS is an important treatment outcome and, from a patient perspective, improves overall QoL, physical functioning, and emotional well-being. PMID- 24218051 TI - Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer. AB - Obesity is associated with basal-like breast cancer (BBC), an aggressive breast cancer subtype. The objective of this study was to determine whether obesity promotes BBC onset in adulthood and to evaluate the role of stromal-epithelial interactions in obesity-associated tumorigenesis. We hypothesized that hepatocyte growth factor (HGF) plays a promoting role in BBC, which express the HGF receptor, c-Met. In C3(1)-T(Ag) mice, a murine model of BBC, we demonstrated that obesity leads to a significant increase in HGF secretion and an associated decrease in tumor latency. By immunohistochemical analysis, normal mammary gland exhibited obesity-induced HGF, c-Met and phospho-c-Met, indicating that the activation of the cascade was obesity-driven. HGF secretion was also increased from primary mammary fibroblasts isolated from normal mammary glands and tumors of obese mice compared to lean. These results demonstrate that obesity-induced elevation of HGF expression is a stable phenotype, maintained after several passages, and after removal of dietary stimulation. Conditioned media from primary tumor fibroblasts from obese mice drove tumor cell proliferation. In co culture, neutralization of secreted HGF blunted tumor cell migration, further linking obesity-mediated HGF-dependent effects to in vitro measures of tumor aggressiveness. In sum, these results demonstrate that HGF/c-Met plays an important role in obesity-associated carcinogenesis. Understanding the effects of obesity on risk and progression is important given that epidemiologic studies imply a portion of BBC could be eliminated by reducing obesity. PMID- 24218052 TI - Contralateral prophylactic mastectomy and survival: report from the National Cancer Data Base, 1998-2002. AB - The use of contralateral prophylactic mastectomy (CPM) has been increasing despite questionable survival benefit. We examined the effect of CPM on survival using the National Cancer Data Base. We examined overall survival on 219,983 mastectomy patients diagnosed with unilateral AJCC Stage 1-III invasive breast cancer between 1998 and 2002 of which 14,994 (7 %) underwent CPM at the time of their index mastectomy. Median follow up time was 5 years. Neoadjuvant and locally advanced breast cancers were excluded. Approximately 4 % underwent CPM in 1998 compared to 9.4 % in 2002, an ~125 % increase. CPM patients were significantly younger than non-CPM patients, on managed care plans, and were treated at high volume centers. The unadjusted hazard ratio (HR) of death was 0.55 (95 % CI 0.52-0.57) for CPM compared to unilateral mastectomy. In a multivariable Cox model adjusting for age, race, stage, grade, histology, insurance, facility characteristics, use of adjuvant hormonal, chemotherapy, and radiotherapy, and year of diagnosis, the adjusted HR was 0.88 (95 % CI 0.83-0.93; p < 0.001) which translated into an absolute 5-year benefit of 2 %. There was a differential effect of CPM by stage and age: HR = 0.88 (95 % CI 0.82-0.94; p < 0.001) in women younger than 70 with stage I/II, and HR = 0.95 (95 % CI 0.88 1.04; p = 0.28) in women with stage III or older than age 69 which translated into an absolute 5-year benefit of 1.3 %. Utilization of hormonal therapy or chemotherapy had no effect on the HR. After adjusting for confounding, the overall survival benefit for CPM is minimal at best. PMID- 24218053 TI - Riociguat: first global approval. AB - Riociguat (Adempas((r))), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). The drug directly stimulates sGC in a nitric oxide independent manner, thereby increasing the sensitivity of sGC to nitric oxide, leading to increased cyclic guanosine monophosphate generation (a key signalling molecule involved in regulating vascular tone, proliferation, fibrosis and inflammation). Riociguat is the world's first approved pharmacotherapy for CTEPH, with its first global approval in this indication occurring in Canada. It has subsequently been approved in the USA for the treatment of patients with CTEPH and also received its first global approval in patients with PAH in the USA. It is undergoing regulatory review for these indications in Europe and for use in patients with CTEPH in Japan. This article summarizes the milestones in the development of riociguat, leading to its first global approvals in patients with CTEPH and PAH. PMID- 24218054 TI - Morphological structure processing during word recognition and its relationship to character reading among third-grade Chinese children. AB - In the present study, we explored the characteristics of morphological structure processing during word recognition among third grade Chinese children and its possible relationship with Chinese character reading. By using the modified priming lexical decision paradigm, a significant morphological structure priming effect was found in the subject analysis when reaction time difference was considered as dependent variable. In the regression analyses, the children's implicit morphological structure processing demonstrated a significant effect on Chinese character reading, even though its effect became non-significant when morphological awareness was entered. We achieved this result after controlling for the children's age, non-verbal intelligence, and phonological awareness. These findings indicate that third grade Chinese children are sensitive to morphological structure information in the processing of compound words. Moreover, such sensitivity is, to some extent, a good predictor of Chinese children's word reading performance. PMID- 24218055 TI - The effect of alcohol on speech production. AB - The present study investigates the effect of acute alcohol consumption on speech in Hungarian subjects. The measures used to reveal these effects were tongue twisters, which were grouped according to their linguistic features. The number and type of speech errors while uttering the tongue-twisters were compared between intoxicated and sober conditions. The results showed that subjects made more speech errors in alcohol influenced than in sober states in all types of the tongue-twisters except for those using foreign words. Changes in the articulation rate, number of pauses and fundamental frequency were investigated as well. In the intoxicated state, no changes were observed in fundamental frequency and articulation rate, while the number of pauses increased. PMID- 24218057 TI - Cigarette graphic warning labels and smoking prevalence in Canada: a critical examination and reformulation of the FDA regulatory impact analysis. AB - BACKGROUND: The estimated effect of cigarette graphic warning labels (GWL) on smoking rates is a key input to the Food and Drug Administration's (FDA) regulatory impact analysis (RIA), required by law as part of its rule-making process. However, evidence on the impact of GWLs on smoking prevalence is scarce. OBJECTIVE: The goal of this paper is to critically analyse FDA's approach to estimating the impact of GWLs on smoking rates in its RIA, and to suggest a path forward to estimating the impact of the adoption of GWLs in Canada on Canadian national adult smoking prevalence. METHODS: A quasi-experimental methodology was employed to examine the impact of adoption of GWLs in Canada in 2000, using the USA as a control. FINDINGS: We found a statistically significant reduction in smoking rates after the adoption of GWLs in Canada in comparison with the USA. Our analyses show that implementation of GWLs in Canada reduced smoking rates by 2.87-4.68 percentage points, a relative reduction of 12.1-19.6%; 33-53 times larger than FDA's estimates of a 0.088 percentage point reduction. We also demonstrated that FDA's estimate of the impact was flawed because it is highly sensitive to the changes in variable selection, model specification, and the time period analysed. CONCLUSIONS: Adopting GWLs on cigarette packages reduces smoking prevalence. Applying our analysis of the Canadian GWLs, we estimate that if the USA had adopted GWLs in 2012, the number of adult smokers in the USA would have decreased by 5.3-8.6 million in 2013. Our analysis demonstrates that FDA's approach to estimating the impact of GWLs on smoking rates is flawed. Rectifying these problems before this approach becomes the norm is critical for FDA's effective regulation of tobacco products. PMID- 24218058 TI - Quality-by-design: are we there yet? AB - In 2012, the Quality-by-Design and Product Performance Focus Group of AAPS conducted a survey to assess the state of adoption and perception of Quality-by Design (QbD). Responses from 149 anonymous individuals from industry-including consultants-(88%), academia (7%), and regulatory body (4%), were collected. A majority of respondents (54% to 76%) reported high frequency of utilization of several tools and most QbD elements outlined by International Conference on Harmonization Q8, with design of experiments, risk assessment, and the quality target product profile ranked as the top three. Over two thirds of respondents agreed that the benefits of QbD included both the positive impact it can have on the patient (78%), as well as on internal processes such as knowledge management (85%), decision making (79%), and lean manufacture (71%). However, more than 50% from industry were neutral about or disagreed with QbD leading to a better return on investment. This suggests that, despite the recognized scientific, manufacture, and patient-related benefits, there is not yet a clearly articulated business case for QbD available. There was a difference of opinion between industry and regulatory agency respondents as to whether a QbD-based submission resulted in increased efficiency of review. These contrasting views reinforce the idea that QbD implementation can benefit from further dialog between industry and regulatory authorities. A majority of respondents from academia indicated that QbD has influenced their research. In total, the results indicate the broad adoption of QbD but also suggest we are yet in a journey and that the process of gathering all experience and metrics required for connecting and demonstrating QbD benefits to all stakeholders is still in progress. PMID- 24218060 TI - Evaluation of the effect of food and beverages on enamel and restorative materials by SEM and Fourier transform infrared spectroscopy. AB - OBJECTIVES: To examine different types of restorative materials used in children as well as primary and permanent teeth enamel when affected by erosive foods. MATERIALS AND METHOD: Buttermilk, fruit yoghurt, Coca-cola, fruit juice, Filtek Z 250, Dyract Extra, Fuji II LC, and Fuji IX and tooth enamel were used. Measurements were performed on 1-day, 1-week, 1-month, 3-month, 6-month time periods by using ATR-FTIR technique and surface of the specimens were examined with SEM. RESULTS: Permanent tooth showed the least change among human tooth samples when compared to restorative materials. Among filler materials, the most change was observed in Fuji IX. In terms of beverages the most changes on absorption peaks obtained from spectra were seen on the samples held in Coca-Cola and orange-juice. CONCLUSION: The exposure of human enamel and restorative materials to acidic drinks may accelerate the degradation process and so reduce the life time of filler materials at equivalent integral exposure times longer than three months. Clinical Relevance Erosive foods and drinks having acidic potential destroy not only tooth enamel but also restorative materials. PMID- 24218059 TI - Functional identification of multiple nucleocytoplasmic trafficking signals in the broad-spectrum resistance protein RPW8.2. AB - Nuclear localization signals (NLSs) and nuclear export signals (NESs) are important intramolecular regulatory elements for protein nucleocytoplasmic trafficking. This regulation confers spatial specificity to signal initiation and transduction in eukaryotic cells and thus is fundamental to the viability of all eukaryotic organisms. Here, we developed a simple and rapid method in which activity of putative NLSs or NESs was reported by subcellular localization of two tandem fluorescent proteins in fusion with the respective NLSs or NESs after agroinfiltration-mediated transient expression in leaves of Nicotiana benthamiana (Nb). We further demonstrated that the predicted NES from amino acid residue (aa) 9 to 22 and the NLS from aa91 to 101 in the broad-spectrum disease resistance protein RPW8.2 possess nuclear export and import activity, respectively. Additionally, by testing overlapping fragments covering the full length of RPW8.2, we identified another NLS from aa65 to 74 with strong nuclear import activity and two tandem non-canonical NESs in the C-terminus with strong nuclear export activity. Taken together, our results demonstrated the utility of a simple method to evaluate potential NLSs and NESs in plant cells and suggested that RPW8.2 may be subject to opposing nucleocytoplasmic trafficking forces for its subcellular localization and functional execution. PMID- 24218061 TI - Dipyrido[3,2-a:2',3'-c]phenazine-based donor-acceptor aromatic heterocyclic compounds with thienyl and triphenylamino chromophores at the 2,7- and/or 10,13 positions. AB - A series of T- and H-shaped donor-acceptor (D-A) types of dipyrido[3,2-a:2',3' c]phenazine (DPPZ)-based molecules, extended by thienyl and triphenylamino chromophores at the 2,7-(bottom) and/or 10,13-positions (top), have been designed and prepared successfully. Synthetic, structural, thermal, spectral, and computational comparisons have been carried out for related compounds because of their adjustable intramolecular charge-transfer properties. It is noted that a pair of structural isomers (5 and 6) has been obtained, respectively, where distinguishable UV/Vis and fluorescence spectra, electrochemical activity, thermal stability, and bandgaps are observed. Furthermore, compounds 6, 8, 10, 11, 13, and 15 exhibit excellent thermal stability, and the Td10 values for them are found to range from 524 to 646 degrees C, which can be regarded as one of the best groups of thermally stable compounds among organic small molecules. In addition, theoretical calculations were performed, and the structure-property relationships were examined to reveal the effects of the position and number of donor arms on the DPPZ acceptor core. PMID- 24218062 TI - Nurse-led versus doctor-led preoperative assessment for elective surgical patients requiring regional or general anaesthesia. AB - BACKGROUND: The organization of elective surgical services has changed in recent years, with increasing use of day surgery, reduced hospital stay and preoperative assessment (POA) performed in an outpatient clinic rather than by a doctor in a hospital ward after admission. Nurse specialists often lead these clinic-based POA services and have responsibility for assessing a patient's fitness for anaesthesia and surgery and organizing any necessary investigations or referrals. These changes offer many potential benefits for patients, but it is important to demonstrate that standards of patient care are maintained as nurses take on these responsibilities. OBJECTIVES: We wished to examine whether a nurse-led service rather than a doctor-led service affects the quality and outcome of preoperative assessment (POA) for elective surgical participants of all ages requiring regional or general anaesthesia. We considered the evidence that POA led by nurses is equivalent to that led by doctors for the following outcomes: cancellation of the operation for clinical reasons; cancellation of the operation by the participant; participant satisfaction with the POA; gain in participant knowledge or information; perioperative complications within 28 days of surgery, including mortality; and costs of POA. We planned to investigate whether there are differences in quality and outcome depending on the age of the participant, the training of staff or the type of surgery or anaesthesia provided. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and two trial registers on 13 February 2013, and performed reference checking and citation searching to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of participants (adults or children) scheduled for elective surgery requiring general, spinal or epidural anaesthesia that compared POA, including assessment of physical status and anaesthetic risk, undertaken or led by nursing staff with that undertaken or led by doctors. This assessment could have taken place in any setting, such as on a ward or in a clinic. We included studies in which the comparison assessment had taken place in a different setting. Because of the variation in service provision, we included two separate comparison groups: specialist doctors, such as anaesthetists; and non-specialist doctors, such as interns. DATA COLLECTION AND ANALYSIS: We used standard methodological approaches as expected by The Cochrane Collaboration, including independent review of titles, data extraction and risk of bias assessment by two review authors. MAIN RESULTS: We identified two eligible studies, both comparing nurse-led POA with POA led by non-specialist doctors, with a total of 2469 participants. One study was randomized and the other quasi-randomized. Blinding of staff and participants to allocation was not possible. In both studies, all participants were additionally assessed by a specialist doctor (anaesthetist in training), who acted as the reference standard. In neither study did participants proceed from assessment by nurse or junior doctor to surgery. Neither study reported on cancellations of surgery, gain in participant information or knowledge or perioperative complications. Reported outcomes focused on the accuracy of the assessment. One study undertook qualitative assessment of participant satisfaction with the two forms of POA in a small number of non-randomly selected participants (42 participant interviews), and both groups of participants expressed high levels of satisfaction with the care received. This study also examined economic modelling of costs of the POA as performed by the nurse and by the non-specialist doctor based on the completeness of the assessment as noted in the study and found no difference in cost. AUTHORS' CONCLUSIONS: Currently, no evidence is available from RCTs to allow assessment of whether nurse-led POA leads to an increase or a decrease in cancellations or perioperative complications or in knowledge or satisfaction among surgical participants. One study, which was set in the UK, reported equivalent costs from economic models. Nurse-led POA is now widespread, and it is not clear whether future RCTs of this POA strategy are feasible. A diagnostic test accuracy review may provide useful information. PMID- 24218063 TI - Multicenter study of Blount disease in Japan by the Japanese Pediatric Orthopaedic Association. AB - BACKGROUND: In order to investigate the epidemiology and features of Blount disease in Japan, the Japanese Pediatric Orthopaedic Association conducted a multicenter study on Blount disease in 2003. METHODS: Questionnaires were sent to 1,350 training hospitals of the Japanese Orthopaedic Association. This study included those with stage I or II diagnosed between 1990 and 2002 and those with stage III or higher diagnosed between 1980 and 2002 based on the Langenskiold classification. The questionnaire items included age at diagnosis, sex, presence or absence of a family history of bowlegs, past history of trauma, birthplace, age when starting to walk, height and weight at the initial presentation, laterality of the affected knee, disease types (infantile or adolescent), treatments, and plain radiographic findings. RESULTS: The results for 212 patients with 296 affected knees were obtained. The disease types were infantile in 190 patients with 270 affected knees and adolescent in 22 patients with 26 affected knees. There were more girls among cases with both types. Among the infantile-type cases, there were more patients with bilaterally affected knees; however, in the adolescent-type cases, there were more patients with unilaterally affected knees. Patients with either type tended to be obese at diagnosis. There was little difference in age at which patients with either type started to walk, compared with the mean age for the general population. Conservative treatment was applied to most infantile-type cases in stage I or II, whereas surgery was performed in all but one of those with stage III or IV of the disease. Most adolescent-type cases underwent surgery. CONCLUSIONS: This was the first multicenter study on Blount disease in Japan. Among 296 knees, the majority of these knees had stage I or II Blount disease. Very few cases had stage III or higher disease, and there were 35 knees with the infantile type and 19 with the adolescent type in the 23 years from 1980 through 2002. PMID- 24218064 TI - Overactive bladder in cervical spondylotic myelopathy. AB - BACKGROUND: Overactive bladder (OAB) is a new disease concept defined by the International Continence Society in 2002. There have been no reports of OAB among patients with cervical spondylotic myelopathy assessed on the basis of symptom questionnaires. METHODS: One-hundred-and-six patients diagnosed with cervical spondylotic myelopathy and treated by use of laminoplasty were examined. The patients were classified into two groups, those identified as having OAB (OAB group) and those identified as not having OAB (non-OAB group), by use of the Overactive Bladder Symptom Score collected before and 1 year after surgery. The clinical results for the two groups were assessed. OAB symptom prevalence and post-operative symptom improvement were investigated 1 year postoperatively. RESULTS: Of the 106 patients, 50 were identified as having OAB (symptom prevalence 47.2%). Of these 50 patients, symptom improvement was observed for only 14 (28%) 1 year after surgery. For both groups good improvement on the basis of the Japanese Orthopedic Association score was observed 1 year postoperatively, but there were no significant differences between them. CONCLUSIONS: Post operative improvement of OAB symptoms in cervical spondylotic myelopathy patients was low, which indicated that OAB was most frequently attributable to non neurogenic and idiopathic, but not neurogenic, causes. It is considered necessary to tell patients with cervical spondylotic myelopathy that the possibility of post-operative OAB symptom improvement is not high when the explanation for informed consent is given before the operation. PMID- 24218065 TI - Antiapoptotic Bcl-2 homolog CED-9 in Caenorhabditis elegans: dynamics of BH3 and CED-4 binding regions and comparison with mammalian antiapoptotic Bcl-2 proteins. AB - Proteins belonging to Bcl-2 family regulate intrinsic cell death pathway. Although mammalian antiapoptotic Bcl-2 members interact with multiple proapoptotic proteins, the Caenorhabditis elegans Bcl-2 homolog CED-9 is known to have only two proapoptotic partners. The BH3-motif of proapoptotic proteins bind to the hydrophobic groove of prosurvival proteins formed by the Bcl-2 helical fold. CED-9 is also known to interact with CED-4, a homolog of the human cell death activator Apaf1. We have performed molecular dynamics simulations of CED-9 in two forms and compared the results with those of mammalian counterparts Bcl XL, Bcl-w, and Bcl-2. Our studies demonstrate that the region forming the hydrophobic cleft is more flexible compared with the CED-4-binding region, and this is generally true for all antiapoptotic Bcl-2 proteins studied. CED-9 is the most stable protein during simulations and its hydrophobic pocket is relatively rigid explaining the absence of functional redundancy in CED-9. The BH3-binding region of Bcl-2 is less flexible among the mammalian proteins and this lends support to the studies that Bcl-2 binds to less number of BH3 peptides with high affinity. The C-terminal helix of CED-9 lost its helical character because of a large number of charged residues. We speculate that this region probably plays a role in intracellular localization of CED-9. The BH4-motif accessibility in CED-9 and Bcl-w is controlled by the loop connecting the first two helices. Although CED-9 adopts the same Bcl-2 fold, our studies highlight important differences in the dynamic behavior of CED-9 and mammalian antiapoptotic homologs. PMID- 24218066 TI - A statistical model for intervertebral disc degeneration: determination of the optimal T2 cut-off values. AB - PURPOSE: The aim of this study was to investigate the possibility of quantitative classification in intervertebral disc degeneration using spin-spin relaxation time (T2) cut-off values with regard to morphological classifications. METHODS: Lumbar magnetic resonance (MR) imaging was performed on 21 subjects (a total of 104 lumbar disks). The T2 relaxation time was measured in the nucleus pulposus using a sagittal multi-echo spin-echo sequence. The morphological classification of disc degeneration was assessed independently by three experienced neuroradiologists according to the Pfirrmann and Schneiderman classifications. Receiver operating characteristic analysis was performed among grades to determine T2 cut-off values in each classification. Intra- and interobserver differences were calculated using kappa statistics. RESULTS: Moderate overall interobserver agreement was found between observers in both the Pfirrmann and Schneiderman classification schemes (kappa 0.46 and 0.51), while intraobserver reliability was substantial to almost perfect. The interobserver reliability was only fair in Pfirrmann grades III and IV (kappa 0.33 and 0.36), but the T2 cut off values still indicated a significant difference between grades (p<0.05). CONCLUSIONS: Interobserver agreement of MR evaluation in patients with intervertebral disc degeneration was only fair to moderate on the classification of more severe disc degeneration in the Pfirrmann and Schneiderman schemes. Based on our results, quantitative T2 cut-off values seem to be a more reliable method to define the degree of disc degeneration, which may help staging intervertebral disc degeneration (IVDD) even if the interobserver reliability is low. PMID- 24218067 TI - Subjective social status, immigrant generation, and cannabis and alcohol use among adolescents. AB - Research indicates that subjective perceptions of socioeconomic status (SES) affect aspects of health and behavior. There has been little research attention to how objective (e.g., education) and subjective aspects of SES may differ in their influence on the substance use of adolescent immigrants. The present study examined whether the associations between subjective SES and substance use, and between parental education and substance use varied by immigrant generation. Data were derived from the 2011 Ontario Student Drug Use and Health Survey, a representative survey of students in the 7th to 12th grade. The sample for this study consisted of 9177 students 12-19 years of age; 48.4 % were female, 66.4 % were White/European, 5.2 % Black/Afro-Caribbean, 16.4 % Asian and 12 % other. Results indicated that subjective SES was more strongly associated with cannabis and alcohol use among first-generation immigrants than among adolescents of other immigrant generations even after adjusting for parental education. First generation immigrants with low subjective SES had a lower probability of cannabis and regular alcohol use, but there was no difference in use between immigrant generations at high subjective SES. The associations between parental education and cannabis and alcohol use did not significantly vary with immigrant generation. The findings highlight the importance of status beliefs among adolescents, particularly among first-generation immigrants, and suggest that further research attention to such beliefs would enhance our understanding of SES and its links to adolescent health risk behaviors. PMID- 24218068 TI - Throwing in the dark: improved prediction of action outcomes following motor training without vision of the action. AB - Traditional models of action understanding emphasise the idea that long-term exposure to a wide array of visual patterns of particular actions allows for effective action anticipation or prediction. More recently, a greater emphasis has been placed on the motor system's role in the perceptual understanding and prediction of action outcomes. There have been attempts to isolate the contributions of visual and motor experience in action prediction, but to date, these studies have relied on comparisons of motor-visual experience to visual only (observational) experience. We conducted a learning study, where visual experience was directly manipulated during practice. Novice participants practised throwing darts to 3 specific areas of a dartboard. A group trained without vision of their action, only feedback about the final landing position, significantly improved in their ability to predict the landing position of a thrown dart, from temporally occluded video clips. The performance of this 'no vision' group did not differ from a Full-vision group and was significantly more accurate than an observation-only and a no-practice control group (with the latter two groups not improving pre- to post-practice). These results suggest that motor experience specifically modulates the perceptual prediction of action outcomes. This is thought to occur through simulative mechanisms, whereby observed actions are mapped onto the observer's own motor representations. PMID- 24218070 TI - FIT testing: an overview. AB - Colorectal cancer (CRC) is a common, but preventable, disease and is the second most common cause of cancer-related deaths in the U.S. CRC screening has proven effective at reducing both the incidence and mortality of this disease, using any of a number of screening tests available. The test options range from the least invasive and least expensive to more invasive and costly options. Fecal occult blood testing is the oldest, least expensive, and least invasive of these options and has evolved from the poorly sensitive standard guaiac test to the newer and diagnostically superior fecal immunochemical test (FIT) for hemoglobin. This article explores the evolutionary history of fecal occult blood testing, examines test performance characteristics among different FOBTs, and evaluates the role of the FIT in programmatic CRC screening. PMID- 24218069 TI - Fas gene variants in childhood acute lymphoblastic leukemia and association with prognosis. AB - Fas molecule is one of the main important molecules involved in apoptotic cell death. Single nucleotide polymorphisms in the promoter of Fas gene at positions 1377G/A and -670 A/G may affect its expression and play an important role in the pathology of leukemia. In the present study the association between these polymorphisms and risk of the development of acute lymphoblastic leukemia (ALL) in children with ALL compared to cancer-free control subjects was examined by polymerase chain reaction- based restriction fragment length polymorphism. The relationship between the polymorphisms and clinical and laboratory features of the patients and response to therapy were determined. No significant differences in genotype and allele frequencies between the patients and the control subjects at positions -670 and -1377 were detected. Evaluation of the prognostic factors revealed an association between the GG genotype at position -670 and liver involvement in ALL patients (p < 0.04). Although patients with -1377 AA genotype showed shorter mean complete remission duration, the result of survival analysis did not reach to be significant. In conclusion, results of this study showed no contribution of Fas genotypes at positions -670 and -1377 to risk of ALL in children. The association of Fas GG genotype at position -670 with liver involvement in the patients may show its important role in prognosis of ALL. PMID- 24218071 TI - Academics and competing interests in H1N1 influenza media reporting. AB - BACKGROUND: Concerns have been raised over competing interests (CoI) among academics during the 2009 to 2010 A/H1N1 pandemic. Media reporting can influence public anxiety and demand for pharmaceutical products. We assessed CoI of academics providing media commentary during the early stages of the pandemic. METHODS: We performed a retrospective content analysis of UK newspaper articles on A/H1N1 influenza, examining quoted sources. We noted when academics made a risk assessment of the pandemic and compared this with official estimations. We also looked for promotion or rejection of the use of neuraminidase inhibitors or H1N1-specific vaccine. We independently searched for CoI for each academic. RESULTS: Academics were the second most frequently quoted source after Ministers of Health. Where both academics and official agencies estimated the risk of H1N1, one in two academics assessed the risk as higher than official predictions. For academics with CoI, the odds of a higher risk assessment were 5.8 times greater than those made by academics without CoI (Wald p value=0.009). One in two academics commenting on the use of neuraminidase inhibitors or vaccine had CoI. The odds of CoI in academics promoting the use of neuraminidase inhibitors were 8.4 times greater than for academics not commenting on their use (Fisher's exact p=0.005). CONCLUSIONS: There is evidence of CoI among academics providing media commentary during the early H1N1 pandemic. Heightened risk assessments, combined with advocacy for pharmaceutical products to counter this risk, may lead to increased public anxiety and demand. Academics should declare, and journalists report, relevant CoI for media interviews. PMID- 24218072 TI - Predictors of help-seeking behaviour among women exposed to violence in Nigeria: a multilevel analysis to evaluate the impact of contextual and individual factors. AB - OBJECTIVES: To simultaneously examine contextual and individual-level predictors of help-seeking behaviour among women exposed to physical and sexual violence in Nigeria. DESIGN: A multi-level cross-sectional study. We fit three 3-level random intercepts models to examine contextual and individual-level characteristics associated with help seeking, simultaneously. SETTING: Nigerian Demographic and Health Survey for 2008. PARTICIPANTS: 5553 women (15-49 years) who reported physical or sexual violence, drawn from 23 715 women in the Nigerian Demographic and Health Survey that responded to questions on violence exposure. MAIN OUTCOME MEASURES: Help seeking to prevent future victimisation was based on self-report. RESULTS: In our sample of women exposed to physical and sexual violence, 39.7% reported that they sought help to stop the perpetrator from hurting them again. Rates of help seeking were geographically patterned by state (range: 12% to 65%). State-level development, measured by the Human Development Index (z-score), was positively associated with help seeking (OR=1.30, 95% CI 1.05 to 1.61), after adjusting for individual-level characteristics. State-level prevalence of violence against women (z-score) was negatively associated with help-seeking (OR=0.68, 95% CI 0.55 to 0.84), suggesting that service providers who may target their programmes to areas with high prevalence of violence, may need to simultaneously address barriers to help seeking. Few individual-level characteristics were associated with help seeking, including wealth, marital status, employment status, ethnicity, history of witnessing domestic violence and relationship to perpetrator. CONCLUSIONS: Efforts to support female survivors of violence should consider broader social and contextual determinants that are associated with help-seeking behaviours. PMID- 24218073 TI - Prenatal exposure to alcohol, and gender differences on child mental health at age seven years. AB - BACKGROUND: It remains uncertain whether exposure to lower doses of alcohol is damaging to the developing fetus. The present study aimed to investigate associations for boys and girls between prenatal exposure to binge drinking and lower doses of alcohol in pregnancy, and parent-reported behavioural and emotional development at age seven. METHODS: This study used data from the Danish National Birth Cohort. Associations between cumulated alcohol exposure and binge drinking from full pregnancy and parent scores on the Strengths and Difficulties Questionnaire (SDQ) measured at age seven were investigated. The SDQ was used as continuous externalising/internalising scores, and as above/below cut-off for the specific scales of hyperactivity/inattention, conduct, emotional and peer problems. Inclusion criteria were information on alcohol exposure from three interviews, SDQ scores at age seven and being born full term (n=37 152). RESULTS: Controlling for relevant confounders, small positive associations were observed between binge drinking and internalising (relative change in mean: 1.04-1.06), externalising scores (relative change in mean: 1.01-1.07), and conduct scores (OR 1.12 to 1.23) for boys. No associations were observed with lower doses of alcohol. CONCLUSIONS: Exposure to binge drinking is weakly associated with impaired behavioural and emotional development measured at age seven. Large differences in background characteristics were observed between the groups defined by cumulated alcohol exposure, leaving the interpretations of findings uncertain. PMID- 24218074 TI - Trends in serum lipids among 5th grade CARDIAC participants, 2002-2012. AB - BACKGROUND: Studies have shown that serum low-density lipoprotein (LDL-C) and non high-density lipoprotein (non-HDL-C) have recently declined in the U.S.A. among adult and child populations despite high obesity prevalence rates. The purpose of this study was to assess whether there was a significant linear decrease in LDL-C and non-HDL-C, but not Body Mass Index (BMI) percentile among a cross-sectional, large, homogenous cohort with consistent methodology over the past decade. METHODS: A total of 47,198 children, mostly between 10 and 11 years old, participating between 2002 and 2012 were examined to assess trends in serum lipid concentration and BMI percentile. RESULTS: For LDL-C, year of screening was significant (p<0.0001) even with the inclusion of gender, age and BMI (all p<0.0001). For non-HDL-C, year of screening was also significant (p<0.0001), even with the inclusion of gender (p=0.0445), age (p<0.0001), BMI (p<0.0001) and systolic blood pressure (p=0.0021). Although some non-linear trends were also significant (e.g., a quartic trend, p<0.001), the linear trend provided the best fit for both cholesterol models. By comparison, we noted general maintenance of BMI percentile over time. CONCLUSIONS: Between 2002 and 2012, among 5th grade Appalachian children, there was a consistent linear decrease in LDL-C and non-HDL C despite continued high prevalence rates of obesity, diabetes and hypertension. The improvement in LDL-C and non-HDL-C could be due to multifactorial causes. PMID- 24218075 TI - Highlight: on the origin of the sexes. PMID- 24218076 TI - Axonal hyperexcitability after combined NGF sensitization and UV-B inflammation in humans. AB - BACKGROUND: Both nerve growth factor (NGF) and ultraviolet-B (UV-B) irradiation sensitize nociceptive nerve endings and increase axonal excitability of nociceptors. Combining NGF and UV-B treatment is supra-additive for sensory sensitization and even caused spontaneous pain in about 70% of the subjects. METHODS: UV-B irradiation was performed at day 21 after intradermal NGF injection in 13 volunteers. Pain thresholds, electrically induced axon reflex erythema and pain (1.5-fold pain threshold, 5-100 Hz) was analysed at days 22, 24, 28, 35, 49 and 70 and correlated to hyperalgesia and spontaneous pain. RESULTS: Electrical pain threshold after combined NGF/UVB was reduced below single treatment at 24 h but not at 72 h post-UV-B irradiation. At the NGF/UV-B site, electrical pain was enhanced at all frequencies compared with single NGF and UV-B sites at 24 and 72 h with pain ratings exceeding control values about twofold to threefold [65 +/- 7 vs. 25 +/- 8 visual analogue scale (VAS) (24 h) and 55 +/- 9 vs. 22 +/- 5 VAS (72 h)]. Hyperalgesia to electrical stimulation correlated with hyperalgesia to pinprick (Spearman r = 0.44; p < 0.001, Bonferroni corr.) and supra-threshold heat (Spearman r = 0.55; p < 0.001) stimulation at 24 h only. Electrical pain thresholds at the NGF/UV-B site weakly correlated to spontaneous pain levels (Spearman r = 0.3; p = 0.025, without Bonferroni correction). In contrast, electrically induced pain or axon reflex erythema did not correlate to spontaneous pain levels. CONCLUSIONS: The combination of NGF and UV-B increases axonal excitability that contributes to hyperalgesia and might also facilitate ongoing spontaneous pain. PMID- 24218077 TI - Laparoscopic repair for a previously unreported form of ventral hernia on the right iliac fossa in an elderly emaciated woman. AB - An 81-year-old emaciated woman was admitted to our hospital with a one-year history of recurrent bilateral inguinal swellings. Palpable lumps were observed not only in bilateral groin areas, but also on the right iliac fossa (RIF) of her abdomen. During a planned transabdominal preperitoneal laparoscopic herniorrhaphy, a previously unreported form of ventral hernia was observed at a position lateral and cranial to the right internal inguinal ring, which probably corresponded to the palpable lump on the RIF. The hernia orifice was 2 cm in diameter, and a vascular structure ran through the orifice. The contents of the hernia consisted of fatty tissue arising from the retroperitoneal tissue. Routine exploration revealed orifices of the following hernias: left indirect, right direct, bilateral femoral, bilateral obturator, and right Spigelian hernia. Her postoperative course was uneventful and a mass on the right lower quadrant disappeared after operation. PMID- 24218078 TI - Single-port laparoscopic extraperitoneal repair of pediatric inguinal hernias and hydroceles by using modified Kirschner pin: a novel technique. AB - BACKGROUND: The development of laparoscopic processus vaginalis repair has provided an alternative approach to the management of inguinal hernia and hydroceles in children. Here we describe our new technique for laparoscopic extraperitoneal ligation of processus vaginalis with subumbilical single-port using a modified Kirschner pin. METHODS: A 5-mm trocar for an operative laparoscope was placed through an infraumbilical incision. A Kirschner pin with a hole in one flat terminal was inserted at the point of the internal inguinal ring. The processus vaginalis was closed extracorporeally by a non-absorbable suture, which was introduced into the abdomen through the Kirschner pin performing dissection within the extraperitoneal space in a series of movements. When a contralateral patent processus vaginalis is present, laparoscopic-assisted extracorporeal ligation is performed during the same operation. RESULTS: Between September 2010 and September 2012, 211 children (130 cases of inguinal hernia and 81 cases of hydrocele) underwent processus vaginalis repair using this novel technique. A contralateral patent processus vaginalis was present and thus simultaneously closed in 20 patients with unilateral inguinal hernias and 12 patients with unilateral hydroceles. The mean operative time was 18 min (8-35 min). The mean follow-up period is 12 months (range 5-24 months), and no recurrence and complications has been observed to date. CONCLUSIONS: This article describes a unique technique of extracorporeal circuit ligation of processus vaginalis using a minimally invasive technique as afforded by a reused modified Kirschner pin. Single-port laparoscopic processus vaginalis repair using this instrument is feasible and seems to be safe. PMID- 24218079 TI - Activity and functions of the human gluteal muscles in walking, running, sprinting, and climbing. AB - It has been suggested that the uniquely large gluteus maximus (GMAX) muscles were an important adaptation during hominin evolution based on numerous anatomical differences between humans and extant apes. GMAX electromyographic (EMG) signals have been quantified for numerous individual movements, but not across the range of locomotor gaits and speeds for the same subjects. Thus, comparing relative EMG amplitudes between these activities has not been possible. We assessed the EMG activity of the gluteal muscles during walking, running, sprinting, and climbing. To gain further insight into the function of the gluteal muscles during locomotion, we measured muscle activity during walking and running with external devices that increased or decreased the need to control either forward or backward trunk pitch. We hypothesized that 1) GMAX EMG activity would be greatest during sprinting and climbing and 2) GMAX EMG activity would be modulated in response to altered forward trunk pitch demands during running. We found that GMAX activity in running was greater than walking and similar to climbing. However, the activity during sprinting was much greater than during running. Further, only the inferior portion of the GMAX had a significant change with altered trunk pitch demands, suggesting that the hip extensors have a limited contribution to the control of trunk pitch movements during running. Overall, our data suggest that the large size of the GMAX reflects its multifaceted role during rapid and powerful movements rather than as a specific adaptation for a single submaximal task such as endurance running. PMID- 24218080 TI - Ribosylation of bovine serum albumin induces ROS accumulation and cell death in cancer line (MCF-7). AB - Formation of advanced glycation end products (AGE) is crucially involved in the several pathophysiologies associated with ageing and diabetes, for example arthritis, atherosclerosis, chronic renal insufficiency, Alzheimer's disease, nephropathy, neuropathy, and cataracts. Because of devastating effects of AGE and the significance of bovine serum albumin (BSA) as a transport protein, this study was designed to investigate glycation-induced structural modifications in BSA and their functional consequences in breast cancer cell line (MCF-7). We incubated D ribose with BSA and monitored formation of D-ribose-glycated BSA by observing changes in the intensity of fluorescence at 410 nm. NBT (nitro blue tetrazolium) assay was performed to confirm formation of keto-amine during glycation. Absorbance at 540 nm (fructosamine) increased markedly with time. Furthermore, intrinsic protein and 8-anilino-1-naphthalenesulfonate (ANS) fluorescence revealed marked conformational changes in BSA upon ribosylation. In addition, a fluorescence assay with thioflavin T (ThT) revealed a remarkable increase in fluorescence at 485 nm in the presence of glycated BSA. This suggests that glycation with D-ribose induced aggregation of BSA into amyloid-like deposits. Circular dichroism (CD) study of native and ribosylated BSA revealed molten globule formation in the glycation pathway of BSA. Functional consequences of ribosylated BSA on cancer cell line, MCF-7 was studied by MTT assay and ROS estimation. The results revealed cytotoxicity of ribosylated BSA on MCF-7 cells. PMID- 24218081 TI - Selective production of methane from aqueous biocarbohydrate streams over a mixture of platinum and ruthenium catalysts. AB - A one-step process for the selective production of methane from low-value aqueous carbohydrate streams is proposed. Sorbitol, used herein as a model compound, is fully converted to methane, CO2 , and a minor amount of H2 by using a physical mixture of Pt and Ru (1:5 in mass basis) at 220 degrees C and 35 bar. This conversion is the result of hydrogenolysis of part of the sorbitol over Ru and the in situ production of H2 through the aqueous-phase reforming of the remaining carbohydrate over Pt. A synergistic effect of the combination of these two catalysts results in the rapid and highly selective conversion of the carbohydrate to methane. This process offers the possibility of upgrading a low value carbohydrate stream into a valuable fuel with no addition of H2. Exergy analysis reveals that nearly 80 % of the exergy of the reactant is recovered as methane. PMID- 24218082 TI - [Hybrid operation theatre from the perspective of neurosurgery]. AB - BACKGROUND: The integration of hybrid operation theatre into neurosurgical and neuroradiological routines is revolutionizing in particular the management of neurovascular emergencies, such as subarachnoid aneurysmal hemorrhage (SAH) or ruptured arteriovenous malformations. RESULTS: The direct interaction between neurosurgeons and neuroradiologists in a joint environment changes and accelerates all diagnostic and therapeutic steps because all relevant procedures, including treatment control can be performed in a single room. Interventions of the skull base or the spine are also a domain of such hybrid theatre. CONCLUSION: As this new concept requires organisational changes throughout the entire patient management, a change of mindset is also needed at the institutional level in order to attain maximum benefits from such a setting. PMID- 24218083 TI - [Minimally invasive video-assisted thyroidectomy: establishment in a thyroid center]. AB - BACKGROUND: This study retrospectively evaluated a series of patients who underwent minimally invasive video-assisted thyroidectomy (MIVAT) during the introduction stage of this surgical technique at the Martha-Maria Hospital in Nuremberg. PATIENTS AND METHODS: The eligibility criteria for MIVAT were a thyroid volume < 25 ml, nodules < 30 mm, no thyroiditis, no preoperative evidence of carcinoma and no previous neck surgery. A retrospective evaluation was performed together with a control group of patients who underwent conventional thyroid surgery during the same time period and included a follow-up for general patient satisfaction and cosmetic results. RESULTS: Between August 2008 and July 2009 a total of 55 patients underwent MIVAT including 8 conversions to open surgery and 45 patients who underwent conventional surgery served as matched controls. No significant differences in terms of perioperative complication rates were found (e.g. recurrent laryngeal nerve palsy, hypocalcemia or secondary hemorrhage). The mean operating time was significantly longer in the MIVAT group (96.8 +/- 3.7 min vs. 69.8 +/- 2.3 min, p = 0.001) whereas a significant decrease in the mean operating time for hemithyroidectomy after 5 months was observed (98.1 +/- 3.77 min vs. 76.0 +/- 4.98 min, p = 0.013). Patients in the MIVAT group were more satisfied with the cosmetic outcome (8.5 +/- 0.3 vs. 8.2 +/- 0.2, p = 0.05) as well as with the overall surgical procedure (9.0 +/- 0.3 vs. 8.6 +/- 0.2, p = 0.02). CONCLUSION: During introduction of the MIVAT procedure a learning effect can be observed which is hallmarked by a decrease in operating time and conversion rate to open surgery. Moreover, no significant differences in terms of main postoperative complications were found so that MIVAT can be considered a safe and feasible technique under the conditions of correct eligibility criteria. PMID- 24218084 TI - MicroRNA expression signature for Satb2-induced osteogenic differentiation in bone marrow stromal cells. AB - Satb2 acts as a potent transcription factor to promote osteoblast differentiation and bone regeneration. Recently, microRNAs (miRNA) have been identified as critical regulators of osteogenic differentiation. This study aimed to identify specific miRNAs and their regulatory roles in the process of Satb2-induced osteogenic differentiation. We studied the differentially expressed miRNAs by Satb2 overexpression in murine bone marrow stromal cells using miRNA microarray. Ten down-regulated miRNAs including miR-27a, miR-125a-5p, and miR-466f-3p, and 18 up-regulated miRNAs including miR-17, miR-20a and miR-210 were found to be differentially expressed and their expression were verified by quantitative real time PCR. The differentially expressed miRNAs were further subjected to gene ontology and KEGG analysis. The highly enriched GOs and KEGG pathway showed target genes of these miRNAs were significantly involved in multiple biological processes (mesenchymal cell differentiation, bone formation, and skeletal development), and several osteogenic pathways (TGF-beta/BMP, MAPK, and Wnt signaling pathway). Finally, miR-27a was selected for target verification and function analysis. BMP2, BMPR1A, and Smad9, members of the TGF-beta/BMP superfamily, which were predicted to be target genes of miR-27a, were confirmed to be significantly up-regulated in Satb2-overexpressing cells by quantitative real time PCR. Overexpression of miR-27a significantly inhibited osteogenesis and repressed BMP2, BMPR1A, and Smad9 expression. In this study, we identified that a number of differentially regulated miRNAs, whose target genes involved in the TGF beta/BMP signaling pathway, play an important role in the early stage of Satb2 induced osteogenic differentiation. PMID- 24218085 TI - Population shift of binding pocket size and dynamic correlation analysis shed new light on the anticooperative mechanism of PII protein. AB - PII protein is one of the largest families of signal transduction proteins in archaea, bacteria, and plants, controlling key processes of nitrogen assimilation. An intriguing characteristic for many PII proteins is that the three ligand binding sites exhibit anticooperative allosteric regulation. In this work, PII protein from Synechococcus elongatus, a model for cyanobacteria and plant PII proteins, is utilized to reveal the anticooperative mechanism upon binding of 2-oxoglutarate (2-OG). To this end, a method is proposed to define the binding pocket size by identifying residues that contribute greatly to the binding of 2-OG. It is found that the anticooperativity is realized through population shift of the binding pocket size in an asymmetric manner. Furthermore, a new algorithm based on the dynamic correlation analysis is developed and utilized to discover residues that mediate the anticooperative process with high probability. It is surprising to find that the T-loop, which is believed to be responsible for mediating the binding of PII with its target proteins, also takes part in the intersubunit signal transduction process. Experimental results of PII variants further confirmed the influence of T-loop on the anticooperative regulation, especially on binding of the third 2-OG. These discoveries extend our understanding of the PII T-loop from being essential in versatile binding of target protein to signal-mediating in the anticooperative allosteric regulation. PMID- 24218086 TI - AMP-activated protein kinase mediates activity-dependent axon branching by recruiting mitochondria to axon. AB - During development, axons are guided to their target areas and provide local branching. Spatiotemporal regulation of axon branching is crucial for the establishment of functional connections between appropriate pre- and postsynaptic neurons. Common understanding has been that neuronal activity contributes to the proper axon branching; however, intracellular mechanisms that underlie activity dependent axon branching remain elusive. Here, we show, using primary cultures of the dentate granule cells, that neuronal depolarization-induced rebalance of mitochondrial motility between anterograde versus retrograde transport underlies the proper formation of axonal branches. We found that the depolarization-induced branch formation was blocked by the uncoupler p-trifluoromethoxyphenylhydrazone, which suggests that mitochondria-derived ATP mediates the observed phenomena. Real-time analysis of mitochondrial movement defined the molecular mechanisms by showing that the pharmacological activation of AMP-activated protein kinase (AMPK) after depolarization increased anterograde transport of mitochondria into axons. Simultaneous imaging of axonal morphology and mitochondrial distribution revealed that mitochondrial localization preceded the emergence of axonal branches. Moreover, the higher probability of mitochondrial localization was correlated with the longer lifetime of axon branches. We qualitatively confirmed that neuronal ATP levels decreased immediately after depolarization and found that the phosphorylated form of AMPK was increased. Thus, this study identifies a novel role for AMPK in the transport of axonal mitochondria that underlie the neuronal activity-dependent formation of axon branches. PMID- 24218087 TI - Mutations in MAPT give rise to aneuploidy in animal models of tauopathy. AB - Tau is a major microtubule-associated protein in brain neurons. Its misfolding and accumulation cause neurodegenerative diseases characterized by brain atrophy and dementia, named tauopathies. Genetic forms are caused by mutations of microtubule-associated protein tau gene (MAPT). Tau is expressed also in nonneural tissues such as lymphocytes. Tau has been recently recognized as a multifunctional protein, and in particular, some findings supported a role in genome stability. In fact, peripheral cells of patients affected by frontotemporal dementia carrying different MAPT mutations showed structural and numerical chromosome aberrations. The aim of this study was to assess chromosome stability in peripheral cell from two animal models of genetic tauopathy, JNPL3 and PS19 mouse strains expressing the human tau carrying the P301L and P301S mutations, respectively, to confirm the previous data on humans. After demonstrating the presence of mutated tau in spleen, we performed standard cytogenetic analysis of splenic lymphocytes from homozygous and hemizygous JNPL3, hemizygous PS19, and relevant controls. Losses and gains of chromosomes (aneuploidy) were evaluated. We detected a significantly higher level of aneuploidy in JNPL3 and PS19 than in control mice. Moreover, in JNPL3, the aneuploidy was higher in homozygotes than in hemizygotes, demonstrating a gene dose effect, which appeared also to be age independent. Our results show that mutated tau is associated with chromosome instability. It is conceivable to hypothesize that in genetic tauopathies the aneuploidy may be present also in central nervous system, possibly contributing to neurodegeneration. PMID- 24218089 TI - Lead in Chinese coals: distribution, modes of occurrence, and environmental effects. AB - Lead (Pb) has gained much attention since the 1970s because of its potential and cumulative toxicity. As one of the most hazardous elements in coals, Pb can be released into the environment during coal mining, processing, and utilization. This study presents a synthesis on the abundance, distribution, modes of occurrence, and environmental impacts of Pb in Chinese coals. Using the expected coal reserves as the weighting factor and based on the previously published Pb content in 4,304 coal samples (including results obtained in our laboratory) from main coalfields or coal mines in China, the weighted mean Pb content in Chinese coals is 13.0 MUg/g, which is higher than that of the American coals (11 MUg/g) and average world coals (7.8 MUg/g). With respect to regional distribution of Pb in Chinese coals, Pb content can be arbitrarily divided into three groups (<20, 20-40, >40 MUg/g). Following this classification, coals from Tibet have the highest average Pb content (128.94 MUg/g). The abundance of Pb in coals varies with coal-forming periods and coal ranks, with the late Triassic and higher rank coals having the highest Pb content, which could be ascribed to regional geochemical differences and later geological evolution as well as magma hydrothermal activities. The enrichment of Pb in coals is influenced by several geological factors, including coal-forming plants, source rocks, hydrothermal fluid, and depositional environment. Pb, dominantly associates with sulfide minerals, especially galena in coals. During coal combustion or pyrolysis, Pb is partly emitted into the atmosphere and partly partitioned to solid residues. Accumulation of Pb from coal utilization in human body could lead to a range of health problems and increase the risk of cancer. PMID- 24218088 TI - New insights into combinational drug therapy to manage congestion in heart failure. AB - Congestion is the most important contributor to morbidity and mortality in heart failure. In patients without congestion, maintaining a neutral sodium balance is imperative to prevent evolving volume overload. Adequate use of neurohumoral blockers, in combination with dietary sodium restriction, is essential and may preclude the need for maintenance diuretic therapy. If volume overload still prevails, loop diuretics remain the mainstay treatment to reduce excessive extracellular volume. However, combinational drug therapy might offer a more attractive alternative to achieve a balanced natriuresis, instead of further uptitration of loop diuretics. Importantly, elevated cardiac filling pressures may be caused by volume misdistribution and impaired venous capacitance, rather than absolute volume overload. Vasodilator therapy to unload the heart, increase venous capacitance, and lower arterial impedance might be interesting in such cases. This review offers a practical approach into current and potential future pharmacologic therapies for managing congestion, focusing on combinational and targeted therapy. PMID- 24218090 TI - Intrinsic allosteric inhibition of signaling proteins by targeting rare interaction states detected by high-pressure NMR spectroscopy. PMID- 24218091 TI - [Surgery under immunosuppression, radiation therapy and chemotherapy]. PMID- 24218092 TI - [Multimodal oncological therapy concepts, chemotherapy and immunosuppressive drugs: effects on surgical morbidity and mortality]. AB - Systemic chemotherapy, targeted therapies and radiotherapy for patients with malignant tumors lead to unfavorable surgical conditions with increased risks of postoperative complications. For gastric cancer and cancer of the esophagogastric junction, surgery after neoadjuvant treatment is associated with a mortality of approximately 5 %. Given the increase in metastatic surgery for colorectal carcinoma, surgeons should be aware of the specific side effects of therapeutic drugs to ensure an optimal course of treatment. The impact of chemotherapy induced hepatic lesions on postoperative development is unclear. Bevacizumab treatment should be stopped at least 5 weeks before surgery to reduce the risk of thromboembolic events, bleeding and wound healing complications. Immunosuppressive and immunomodulating agents alter wound healing and preoperative alterations should be carefully evaluated. For patients with chronic corticosteroid therapy, perioperative supplementation should be considered when planning surgery as well as routine dosages. PMID- 24218093 TI - [Morbidity and mortality of hyperthermic intraperitoneal chemoperfusion]. AB - Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) is a treatment option for peritoneal surface malignancy. Despite the survival benefits, this treatment was previously associated with a high morbidity and mortality rates, and the perception of the poor perioperative outcomes associated with this regimen remains. Careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment.However, for this treatment to be accepted as standard of care, teams undertaking this treatment strategy must aim to minimize morbidity and mortality by learning from the experience of established centers and using the "global learning curve". The HIPEC Registry and accreditation of centers will improve the quality of the treatment. PMID- 24218095 TI - [Operative therapy of secondary ventral hernia: technical principles]. AB - Secondary ventral hernia or incisional hernia occurs in at least 20 % of cases after laparotomy and most patients are symptomatic. The pathogenesis of incisional hernia is believed to be based on a defect in collagen synthesis indicating the necessity of covering the whole original incision with a non resorbable, macroporous mesh. These meshes can be used on top of the fascia (onlay), in a retromuscular fashion (sublay) or intraperitoneally (IPOM). The IPOM technique is the preferred procedure during laparoscopic repair of ventral hernias. The clear advantage of the laparoscopic approach is the dramatically reduced rate of wound complications, especially infections. Major defects of the abdominal wall require plastic reconstruction with the component separation technique in both anterior and posterior approaches. The component separation technique must be combined with retromuscular mesh augmentation enabling a recurrence rate of less than 10 % and an acceptable morbidity to be achieved. PMID- 24218096 TI - Comparison of the effectiveness of cognitive behavioral therapy for depression among older versus younger veterans: results of a national evaluation. AB - OBJECTIVES: The effectiveness of cognitive behavioral therapy for depression (CBT D) among older adults in routine clinical settings has received limited attention. The current article examines and compares outcomes of older versus younger veterans receiving CBT-D nationally. METHOD: Patient outcomes were assessed using the Beck Depression Inventory-II and World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised. RESULTS: A total of 764 veterans aged 18-64 and 100 veterans aged 65+ received CBT-D; 68.0% of older and 68.3% of younger patients completed all sessions or finished early due to symptom relief, and mean depression scores declined from 27.0 (standard deviation [SD] = 10.7) to 16.2 (SD = 12.4) in the older group and from 29.1 (SD = 11.2) to 17.8 (SD = 13.5) in the younger group. Within-group effect sizes were d = 1.01 for both groups. Significant increases in quality of life and therapeutic alliance were observed for both groups. DISCUSSION: CBT-D resulted in significant improvements in depression and quality of life among older patients. Outcomes and rate of attrition were equivalent to younger patients. Findings indicate that CBT-D is an effective and acceptable treatment for older veterans in real-world settings with often high levels of depression. PMID- 24218097 TI - Evolution of structure and properties of granules containing microcrystalline cellulose and polyvinylpyrrolidone during high-shear wet granulation. AB - Granulation behavior of microcrystalline cellulose (MCC) in the presence of 2.5% polyvinylpyrrolidone (PVP) was systematically studied. Complex changes in flowability and tabletability of lubricated MCC granules are correlated to changes in intragranular porosity, morphology, surface smoothness, size distribution, and specific surface area (SSA). With 2.5% PVP, the use of 45% granulation water leads to 84% reduction in tablet tensile strength and 76% improvement in powder flow factor. The changes in powder performance are explained by granule densification and surface smoothing. The granulating water level corresponding to the onset of overgranulation, 45%, is significantly lower than the 70% water required for unlubricated MCC granules without PVP. At more than 45% water levels, MCC-PVP granules flow well but cannot be compressed into intact tablets. Such changes in powder performance correspond to the rapid growth into large and dense spheres with smooth surface. Compared with MCC alone, the onset of the phase of fast granule size enlargement occurs at a lower water level when 2.5% PVP is used. Although the use of 2.5% PVP hastens granule nucleation and growth rate, the mechanisms of overgranulation are the same, that is, size enlargement, granule densification, surface smoothing, and particle rounding in both systems. PMID- 24218098 TI - The origins of SPECT and SPECT/CT. AB - Single photon emission computed tomography (SPECT) has a long history of development since its initial demonstration by Kuhl and Edwards in 1963. Although clinical utility has been dominated by the rotating gamma camera, there have been many technological innovations with the recent popularity of organ-specific dedicated SPECT systems. The combination of SPECT and CT evolved from early transmission techniques used for attenuation correction with the initial commercial systems predating the release of PET/CT. The development and acceptance of SPECT/CT has been relatively slow with continuing debate as to what cost/performance ratio is justified. Increasingly, fully diagnostic CT is combined with SPECT so as to facilitate optimal clinical utility. PMID- 24218099 TI - Ischaemic memory imaging using metabolic radiopharmaceuticals: overview of clinical settings and ongoing investigations. AB - "Ischaemic memory" is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). beta-Methyl-p [(123)I]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of (123)I-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with (18)F-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations. PMID- 24218100 TI - Cerebral vasculopathy in a Chinese family with neurofibromatosis type I mutation. AB - Neurofibromatosis type I (NF1) is a hereditary, autosomal dominant, neurocutaneous syndrome that is attributed to NF1 gene mutation. NF1 has been associated with scoliosis, macrocephaly, pseudoarthrosis, short stature, mental retardation, and malignancies. NF1-associated vasculopathy is an uncommon and easily-overlooked presentation. Examination of a Chinese family affected by NF1 combined with cerebral vessel stenosis and/or abnormality suggested a possible relationship between NF1 and vessel stenosis. To determine which NF1 gene mutation is associated with vascular lesions, particularly cerebral vessel stenosis, we examined one rare family with combined cerebral vessel lesions or maldevelopment. Vascular lesions were detected using transcranial Doppler sonography and digital subtraction angiography in family members. Next, denaturing high-performance liquid chromatography and sequencing were used to screen for NF1 gene mutations. The results revealed a nonsense mutation, c.541C>T, in the NF1 gene. This mutation truncated the NF1 protein by 2659 amino acid residues at the C-terminus and co-segregated with all of the patients, but was not present in unaffected individuals in the family. Exceptionally, three novel mutations were identified in unaffected family members, but these did not affect the product of the NF1 gene. Thus the nonsense mutation, c.541C>T, located in the NF1 gene could constitute one genetic factor for cerebral vessel lesions. PMID- 24218101 TI - Developments in CD4 and viral load monitoring in resource-limited settings. AB - CD4 counts and human immunodeficiency virus (HIV) load testing are essential components of HIV care, and making these tests available in resource-limited settings is critical to the roll-out of HIV treatment globally. Until recently, the evidence supporting the importance of laboratory monitoring in resource limited settings was lacking, but there is now a consensus emerging that testing should become routine to ensure the longevity of treatment programs. Low-cost, point-of-care testing offers the potential to fill this role as it potentially improves all aspects of HIV care, ranging from the diagnosis and staging of HIV infection in both infants and adults to monitoring for treatment failure once antiretroviral therapy has been initiated. It is imperative for low-cost solutions to become a reality, but it is equally imperative that close scrutiny be given to each new device that hits the market to ensure they perform optimally in all settings. PMID- 24218102 TI - Elevated levels of IL-23 in a subset of patients with post-lyme disease symptoms following erythema migrans. AB - BACKGROUND: The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. METHODS: The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. RESULTS: At study entry, significant differences between groups were observed for the type 1 helper T cell (TH1)-associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (TH17)-associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P <= .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels >= 230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. CONCLUSIONS: High TH1-associated responses correlated with more effective immune mediated spirochetal killing, whereas high TH17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease. PMID- 24218103 TI - Accuracy of administrative code data for the surveillance of healthcare associated infections: a systematic review and meta-analysis. AB - Administrative code data (ACD), such as International Classifications of Diseases, Ninth Revision, Clinical Modification codes, are widely used in surveillance and public reporting programs that seek to identify healthcare associated infections (HAIs); however, little is known about their accuracy. This systematic review summarizes evidence for the accuracy of ACD for the detection of selected HAIs, including catheter-associated urinary tract infection, Clostridium difficile infection (CDI), central line-associated bloodstream infection, ventilator-associated pneumonia/events, postprocedure pneumonia, methicillin-resistant Staphylococcus aureus, and surgical site infections (SSIs). We conducted meta-analysis for SSIs and CDIs, where acceptable numbers of primary studies were available. For these 2 conditions, ACD have moderate sensitivity and high specificity, but evidence for detection of other HAIs is limited. With current low prevalence of HAIs, the positive predictive value of ACD algorithms would be low. ACD may be inaccurate for detection of many HAIs and should be used cautiously for surveillance and reporting purposes. PMID- 24218104 TI - Glia activation and its role in oxidative stress. AB - Glia activation and neuroinflamation are major factors implicated in the aetiology of most neurodegenerative diseases (NDDs). Several agents and toxins have been known to be capable of inducing glia activation an inflammatory response; most of which are active substances that can cause oxidative stress by inducing production of reactive oxygen species (ROS). Neurogenesis on the other hand involves metabolic and structural interaction between neurogenic and glia cells of the periventricular zone (PVZ); a region around the third ventricle. This study investigates glia activation (GFAP), cell proliferation (Ki-67) and neuronal metabolism (NSE) during neurogenesis and oxidative stress by comparing protein expression in the PVZ against that of the parietal cortex. Adult Wistar Rats were treated with normal saline and 20 mg/Kg KCN for 7 days. The tissue sections were processed for immunohistochemistry to demonstrate glia cells (anti Rat-GFAP), cell proliferation (anti Rat-Ki-67) and neuronal metabolism (anti Rat NSE) using the antigen retrieval method. The sections from Rats treated with cyanide showed evidence of neurodegeneration both in the PVZ and cortex. The distribution of glia cells (GFAP), Neuron specific Enolase (NSE) and Ki-67 increased with cyanide treatment, although the increases were more pronounced in the neurogenic cell area (PVZ) when compared to the cortex. This suggests the close link between neuronal metabolism and glia activation both in neurogenesis and oxidative stress. PMID- 24218105 TI - Effects of acute and chronic inhalation of paint thinner in mice: behavioral and immunohistochemical study. AB - Abuse of volatile inhalants has become a worldwide issue mainly among adolescents of low income social class. Acute and chronic exposure to these substances results in serious neurological and behavioral impairments. Although real exposure consists largely of simultaneous inhalation of multiple solvents, the vast majority of basic research studies have evaluated the actions of a single volatile component leaving the behavioral and neuronal effects of chemical mixture not fully understood. In this study, we investigated the acute behavioral effects of 300, 450 and 600 ppm of paint thinner inhalation on anxiety, locomotor activity and spatial memory. Additionally, the cognitive impairments related to chronic exposure of the same concentrations of thinner for 45 days were assessed. To understand the neuronal correlates of acute exposure to thinner, we used c-Fos immunohistochemistry as an endogenous marker of neuronal activation following 600 ppm of thinner. The results reveal that (i) chronically thinner exposed mice showed cognitive deficits in Morris water maze and object recognition tasks; (ii) acute inhalation of thinner induces a wide range of behavioral changes. These changes include an anxiolytic effect toward the aversive environmental bright light and a dose dependent effect on explorative locomotion. The wide range of behavioral alterations induced by acute thinner inhalation is consistent with the widespread distribution of thinner-induced c-Fos expression in multiple brain structures. PMID- 24218106 TI - MeCP2-mediated alterations of striatal features accompany psychomotor deficits in a mouse model of Rett syndrome. AB - Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Affected individuals develop motor deficits including stereotypic hand movements, impaired motor learning and difficulties with movement. To understand the neural mechanisms of motor deficits in RTT, we characterized the molecular and cellular phenotypes in the striatum, the major input nucleus of the basal ganglia that controls psychomotor function, in mice carrying a null allele of Mecp2. These mice showed significant hypoactivity associated with impaired motor coordination and motor skill learning. We found that dopamine content was significantly reduced in the striatum of Mecp2 null mice. Reduced dopamine was accompanied by down-regulation of tyrosine hydroxylase and up-regulation of dopamine D2 receptors, particularly in the rostral striatum. We also observed that loss of MeCP2 induced compartment specific alterations in the striatum, including reduced expression of MU-opioid receptors in the striosomes and increased number of calbindin-positive neurons in the striatal matrix. The total number of parvalbumin-positive interneurons and their dendritic arborization were also significantly increased in the striatum of Mecp2 null mice. Together, our findings support that MeCP2 regulates a unique set of genes critical for modulating motor output of the striatum, and that aberrant structure and function of the striatum due to MeCP2 deficiency may underlie the motor deficits in RTT. PMID- 24218107 TI - Packing interface energetics in different crystal forms of the lambda Cro dimer. AB - Variation among crystal structures of the lambda Cro dimer highlights conformational flexibility. The structures range from a wild type closed to a mutant fully open conformation, but it is unclear if each represents a stable solution state or if one may be the result of crystal packing. Here we use molecular dynamics (MD) simulation to investigate the energetics of crystal packing interfaces and the influence of site-directed mutagenesis on them in order to examine the effect of crystal packing on wild type and mutant Cro dimer conformation. Replica exchange MD of mutant Cro in solution shows that the observed conformational differences between the wild type and mutant protein are not the direct consequence of mutation. Instead, simulation of Cro in different crystal environments reveals that mutation affects the stability of crystal forms. Molecular Mechanics Poisson-Boltzmann Surface Area binding energy calculations reveal the detailed energetics of packing interfaces. Packing interfaces can have diverse properties in strength, energetic components, and some are stronger than the biological dimer interface. Further analysis shows that mutation can strengthen packing interfaces by as much as ~5 kcal/mol in either crystal environment. Thus, in the case of Cro, mutation provides an additional energetic contribution during crystal formation that may stabilize a fully open higher energy state. Moreover, the effect of mutation in the lattice can extend to packing interfaces not involving mutation sites. Our results provide insight into possible models for the effect of crystallization on Cro conformational dynamics and emphasize careful consideration of protein crystal structures. PMID- 24218108 TI - A blueprint for research on Shankopathies: a view from research on autism spectrum disorder. AB - Autism spectrum disorders (ASD) are associated with mutations in a host of genes including a number that function in synaptic transmission. Phelan McDermid syndrome involves mutations in SHANK3 which encodes a protein that forms a scaffold for glutamate receptors at the synapse. SHANK3 is one of the genes that underpins the synaptic hypothesis for ASD. We discuss this hypothesis with a view to the broader context of ASD and with special emphasis on highly penetrant genetic disorders including Shankopathies. We propose a blueprint for near and longer-term goals for fundamental and translational research on Shankopathies. PMID- 24218109 TI - Cholesterol-responsive metabolic proteins are required for larval development in Caenorhabditis elegans. AB - Caenorhabditis elegans, a cholesterol auxotroph, showed defects in larval development upon cholesterol starvation (CS) in a previous study. To identify cholesterol-responsive proteins likely responsible for the larval arrest upon CS, a comparative proteomic analysis was performed between C. elegans grown in normal medium supplemented with cholesterol (CN) and those grown in medium not supplemented with cholesterol (cholesterol starvation, CS). Our analysis revealed significant change (more than 2.2-fold, p < 0.05) in nine proteins upon CS. Six proteins were down-regulated [CE01270 (EEF-1A.1), CE08852 (SAMS-1), CE11068 (PMT 2), CE09015 (ACDH-1), CE12564 (R07H5.8), and CE09655 (RLA-0)], and three proteins were up-regulated [CE29645 (LEC-1), CE16576 (LEC-5), and CE01431 (NEX-1)]. RNAi phenotypes of two of the down-regulated genes, R07H5.8 (adenosine kinase) and rla 0 (ribosomal protein), in CN were similar to that of larval arrest in CS, and RNAi of a down-regulated gene, R07H5.8, in CS further enhanced the effects of CS, suggesting that down-regulation of these genes is likely responsible for the larval arrest in CS. All three up-regulated genes contain putative DAF-16 binding sites and mRNA levels of these three genes were all decreased in daf-16 mutants in CN, suggesting that DAF-16 activates expression of these genes. PMID- 24218110 TI - Highly efficient dye-sensitized solar cells based on panchromatic ruthenium sensitizers with quinolinylbipyridine anchors. AB - Panchromatic Ru(II) sensitizers TF-30-TF-33 bearing a new class of 6-quinolin-8 yl-2,2'-bipyridine anchor were synthesized and tested under AM1.5 G simulated solar irradiation. Their increased pi conjugation relative to that of the traditional 2,2':6',2''-terpyridine-based anchor led to a remarkable improvement in absorptivity across the whole UV-Vis-NIR spectral regime. Furthermore, the introduction of a bulky tert-butyl substituent on the quinolinyl fragment not only led to an increase in the JSC value owing to the suppression of dye aggregation, but remarkably also resulted in no loss in VOC in comparison with the reference sensitizer containing a tricarboxyterpyridine anchor. The champion sensitizer in DSC devices was found to be TF-32 with a performance of JSC =19.2 mA cm(-2) , VOC =740 mV, FF=0.72, and eta=10.19 %. This 6-quinolin-8-yl-2,2' bipyridine anchor thus serves as a prototype for the next generation of Ru(II) sensitizers with any tridentate ancillary. PMID- 24218111 TI - After the cure: management of HCV after achievement of SVR. AB - Co-infection with HIV and HCV is associated with accelerated progression of liver disease and increased complications compared with HCV infection alone. Treatment of HCV and achievement of a sustained virologic response (SVR) can improve outcomes in these patients. Even after clearance of the hepatitis C virus, however, patients remain at risk, albeit diminished, for the complications of chronic liver disease. As such, longitudinal monitoring of treated patients remains important for clinicians caring for this population. This article summarizes the benefits and persistent risks after attaining SVR. It reviews the natural history of fibrosis and addresses the monitoring and management of progressive liver disease. PMID- 24218113 TI - Aircraft mass budgeting to measure CO2 emissions of Rome, Italy. AB - Aircraft measurements were used to estimate the CO2 emission rates of the city of Rome, assessed against high-resolution inventorial data. Three experimental flights were made, composed of vertical soundings to measure Planetary Boundary Layer (PBL) properties, and circular horizontal transects at various altitudes around the city area. City level emissions and associated uncertainties were computed by means of mass budgeting techniques, obtaining a positive net CO2 flux of 14.7 +/- 4.5, 2.5 +/- 1.2, and 10.3 +/- 1.2 MUmol m(-2) s(-1) for the three flights. Inventorial CO2 fluxes at the time of flights were computed by means of spatial and temporal disaggregation of the gross emission inventory, at 10.9 +/- 2.5, 9.6 +/- 1.3, and 17.4 +/- 9.6 MUmol m(-2) s(-1). The largest differences between the two dataset are associated with a greater variability of wind speed and direction in the boundary layer during measurements. Uncertainty partitioned into components related to horizontal boundary flows and top surface flow, revealed that the latter dominates total uncertainty in the presence of a wide variability of CO2 concentration in the free troposphere (up to 7 ppm), while it is a minor term with uniform tropospheric concentrations in the study area (within 2 ppm). Overall, we demonstrate how small aircraft may provide city level emission measurements that may integrate and validate emission inventories. Optimal atmospheric conditions and measurement strategies for the deployment of aircraft experimental flights are finally discussed. PMID- 24218112 TI - Considerations in the pharmacologic treatment and prevention of neonatal sepsis. AB - The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis. PMID- 24218114 TI - Intravenous immunoglobulin and rituximab for cerebellar ataxia with glutamic acid decarboxylase autoantibodies. AB - Cerebellar ataxia associated with glutamic acid decarboxylase autoantibodies (GAD ab) is a rare and usually slow progressive disease with moderate to severe gait and limb ataxia, dysarthria, and nystagmus. The treatment for this condition is still being discussed. We report the cases of three patients with GAD-ab cerebellar ataxia treated successively with intravenous immunoglobulin (IVIg) and rituximab. Symptoms improved in one case after rituximab therapy and were stabilized in another after a combined therapy of IVIg and rituximab. The third patient continued to worsen despite these treatments. We conclude that IVIg and rituximab therapy could improve or stabilize GAD-ab cerebellar ataxia. Early treatment, the lack of cerebellar atrophy on magnetic resonance imaging, and a subacute onset of the symptoms could be decisive prognostic factors. PMID- 24218115 TI - Wear in total knee arthroplasty--just a question of polyethylene?: Metal ion release in total knee arthroplasty. AB - PURPOSE: Biological reactions against wear particles are a common cause for revision in total knee arthroplasty. To date, wear has mainly been attributed to polyethylene. However, the implants have large metallic surfaces that also could potentially lead to metal wear products (metal ions and debris). The aim of this study was to determine the local release of cobalt, chromium, molybdenum and titanium in total knee arthroplasty during a standard knee wear test. METHODS: Four moderately conforming fixed-bearing implants were subjected to physiological loadings and motions for 5*10(6) walking cycles in a knee wear simulator. Polyethylene wear was determined gravimetrically and the release of metallic wear products was measured using high resolution-inductively coupled plasma-mass spectrometry. RESULTS: A polyethylene wear rate of 7.28 +/- 0.27 mg/10(6) cycles was determined and the cumulative mass of released metals measured 1.63 +/- 0.28 mg for cobalt, 0.47 +/- 0.06 mg for chromium, 0.42 +/- 0.06 mg for molybdenum and 1.28 +/- 0.14 mg for titanium. CONCLUSION: For other metallic implants such as metal-on-metal total hip arthroplasty, the metal wear products can interact with the immune system, potentially leading to immunotoxic effects. In this study about 12 % by weight of the wear products were metallic, and these particles and ions may become clinically relevant for patients sensitive to these materials in particular. Non-metallic materials (e.g. ceramics or suitable coatings) may be considered for an alternative treatment for those patients. PMID- 24218116 TI - On the cellular uptake and membrane effect of the multifunctional peptide, TatLK15. AB - Recently, the multifunctional peptide TatLK15 resulting from the fusion of the cell penetrating peptide Tat and the amphipathic peptide LK15 was shown to be efficient at mediating siRNA and shRNA delivery in leukemia cells to silence the bcr-abl oncoprotein. The present study focused on TatLK15 peptide cellular uptake and defining conditions for its use within a range of doses exhibiting minimal toxicity. The initial part of the study carried out in solution confirmed that the insertion of a glycine bridge allowed retention of the LK15 alpha-helicity, and fluorescence correlation spectroscopy did not reveal preferential conformations at the studied concentrations. In the second part, TatLK15 uptake mechanisms appeared peptide dose- and cell line- dependent as well as requiring membrane potential. Below a critical dose, TatLK15 toxicity appeared limited for approximately three hours as demonstrated by the combined use of lactate dehydrogenase release, MTT assays, and time-dependent observation of membrane impermeant dye uptake using high content screening apparatus. Furthermore, toxicity was observed to occur rapidly at higher peptide doses. Finally, a comparison between TatLK15 and another Tat amphipathic peptide construct suggested that alpha-helix content should be viewed as a key element in the development of similar peptides. PMID- 24218117 TI - Utility of serodiagnostics designed for use in the United States for detection of Lyme borreliosis acquired in Europe and vice versa. AB - Although two-tier testing is standard practice in both the United States and Europe for the serologic diagnosis of Lyme borreliosis (LB), the test kits generally differ. The purpose of this study was to determine if the testing used in the United States will detect LB acquired in Europe and vice versa. Testing was performed on a convenience sample of archived sera from 40 LB patients from Austria and 39 from the United States, using first- and second-tier test kits from both the United States and Europe. The sensitivity of four first-tier tests from Europe and two first-tier tests from the United States was similar. Thus, two-tier testing was compared to the C6 ELISA as the first-tier test, since it is licensed in both the United States and Europe. The sensitivity of C6 two-tier testing with US assays was 9/40 (22.5 % [95 % CI 10.8-38.5 %]) for detection of LB acquired in Europe, and just 20.0 % (95 % CI 2.5-55.6 %) in the ten European patients with neurologic involvement. These results differed significantly from the sensitivity of European C6 two-tier testing that was 70.0 % (95 % CI 53.5 83.4 %) overall (p < 0.001) and 90.0 % (95 % CI 55.5-99.7 %) for the European patients with neurologic manifestations specifically (p = 0.016). In contrast, the sensitivity of European and US C6 two-tier testing was similar for detection of LB acquired in the United States. Two-tier serologic testing with the US test kits may be unsatisfactory for detection of LB acquired in Europe. First-tier testing with an assay such as the C6 ELISA should be considered as a stand-alone diagnostic strategy in such cases. PMID- 24218118 TI - Disconnection of a basal ganglia circuit in juvenile songbirds attenuates the spectral differentiation of song syllables. AB - Similar to language acquisition by human infants, juvenile male zebra finches (Taeniopygia guttata) imitate an adult (tutor) song by transitioning from repetitive production of one or two undifferentiated protosyllables to the sequential production of a larger and spectrally heterogeneous set of syllables. The primary motor region that controls learned song is driven by a confluence of input from two premotor pathways: a posterior pathway that encodes the adult song syllables and an anterior pathway that includes a basal ganglia (BG)-thalamo cortical circuit. Similar to mammalian motor-learning systems, the songbird BG circuit is thought to be necessary for shaping juvenile vocal behaviour (undifferentiated protosyllables) toward specific targets (the tutor's song syllables). Here, we tested the hypothesis that anterior pathway activity contributes to the process of protosyllable differentiation. Bilateral ablation of lateral magnocellular nucleus of the anterior nidopallium (LMAN) was used to disconnect BG circuitry at ages before protosyllable production and differentiation. Comparison to surgical controls revealed that protosyllables fail to differentiate in birds that received juvenile LMAN ablation--the adult songs of birds with >80% bilateral LMAN ablation consisted of only one or two syllables produced with the repetitive form and spectral structure that characterizes undifferentiated protosyllables in normal juveniles. Our findings support a role for BG circuitry in shaping juvenile vocal behaviour toward the acoustic structure of the tutor song and suggest that posterior pathway function remains in an immature "default" state when developmental interaction with the anterior pathway is reduced or eliminated. PMID- 24218119 TI - Echo-guided mitral repair. AB - BACKGROUND: Echocardiography is available in the most basic healthcare environments. Mitral repair is potentially curative and, when possible, recommended over replacement. The efficacy of echo-guided repair has not been established. METHODS AND RESULTS: We developed a succinct set of precisely defined images observed to be highly concordant with intraoperative findings. These images guided intervention on 237 consecutive patients. None were lost to follow-up, and serial echocardiography was obtained on all repairs. This analysis includes 2037 echocardiograms. The intent to repair or replace was documented preoperatively in 98.7%. Concordance was associated with successful repair (97.8% versus 57.1%; P=0.001). Three-dimensional concordance was higher than 2 dimensional (100% versus 94.4%; P=0.05). Echocardiography guided a graduated surgical approach for degenerative and myopathic repairs by quantifying segmental prolapse, anterior leaflet closing angles, and tenting for integration of secondary chord lysis (P<0.001) and commissural width (P<0.01). Repair rates increased from 46.5% to 77.6% (P<0.001). Concomitant Society of Thoracic Surgeons rates were 46.6% (versus unguided 46.5%; P=0.99) and 54.9% (versus echo guided 77.6%; P<0.001). Repair was successful in 91.5% of isolated echo-guided mitral operations (versus concomitant Society of Thoracic Surgeons 70.0%; P<0.001). Echo guided repair rates for degenerative, myopathic, and inflammatory diseases were 99.0%, 97.1%, and 84.2% with linearized annual recurrent regurgitation of 0.63%, 2.19%, and 4.37%, respectively. CONCLUSIONS: Echocardiography can reliably identify repairable mitral disease and guide intervention. Echo-guided repair is associated with a higher rate of initial success than unguided historical and concomitant national controls. Three-dimensional echo improves concordance. Secondary chord lysis is associated with durable repair and may prevent ventricular remodeling. PMID- 24218120 TI - Serial reversal learning in bumblebees (Bombus impatiens). AB - Bumblebees are capable of rapidly learning discriminations, but flexibility in bumblebee learning is less well understood. We tested bumblebees (Bombus impatiens) on a serial reversal learning task. A serial reversal task requires learning of an initial discrimination between two differentially rewarded stimuli, followed by multiple reversals of the reward contingency between stimuli. A reduction in errors with repeated reversals in a serial reversal task is an indicator of behavioural flexibility. Bees were housed in a large indoor environment and tested during foraging flights. Testing free-flying bees allowed for large numbers of trials and reversals. All bees were trained to perform a simultaneous discrimination between two colours for a nectar reward, followed by nine reversals of this discrimination. Results showed that bumblebees reduced errors and improved their performance across successive reversals. A reduction in perseverative errors was the major cause of the improvement in performance. Bees showed a slight increase in error rate in their final trials, perhaps as a consequence of increasing proactive interference, but proactive interference may also have contributed to the overall improvement in performance across reversals. Bumblebees are thus capable of behavioural flexibility comparable to that of other animals and may use proactive interference as a mechanism of behavioural flexibility in varying environments. PMID- 24218121 TI - Ring-tailed lemurs (Lemur catta) exploit information about what others can see but not what they can hear. AB - Studies suggest that haplorhine primates are sensitive to what others can see and hear. Using two experimental designs, we tested the hypothesis that ring-tailed lemurs (N = 16) are also sensitive to the visual and auditory perception of others. In the first task, we used a go/no-go design that required lemurs to exploit only auditory information. In the second task, we used a forced-choice design where lemurs competed against a human who would prevent them from obtaining food if their approaches were detected. Subjects were given the choice of obtaining food silently or noisily when the competitor's back was turned. They were also given the choice to obtain food when the competitor could either see them or not. Here, we replicate the findings of previous studies indicating that ring-tailed lemurs are sensitive to whether they can be seen; however, we found no evidence that subjects are sensitive to whether others can hear them. Our findings suggest that ring-tailed lemurs converge with haplorhine primates only in their sensitivity to the visual information of others. The results emphasize the importance of investigating social cognition across sensory domains in order to elucidate the cognitive mechanisms that underlie apparently complex social behavior. These findings also suggest that the social dynamics of haplorhine groups impose greater cognitive demands than lemur groups, despite similarities in total group size. PMID- 24218122 TI - Deregulation from CD4+ memory T cells to regulatory cells in patients with chronic renal failure: a pilot study. AB - BACKGROUND: The aim of this study was to elucidate whether the CD4+ memory T (Tm) cells differentiation to regulatory T cells (Tregs) play a role in the immunological defects in patients with chronic kidney disease (CKD), and if the oxidized low-density lipoprotein (oxLDL) had affect on on CD4+ Tm cells and Tregs apoptosis in these subjects. METHODS: CD4+ Tm cells and Tregs were detected by flow cytometry in each group of ten subjects. Apoptosis was measured by flow cytometry and confirmed by Western blotting. RESULTS: The oxLDL concentration was significantly higher in CKD stage 4 (CKD4) patients than in controls, particularly in hemodialysis (HD) subjects (P < 0.001, respectively). In total, 100 MUg/ml oxLDL significantly inhibited the CD4+ Tm cell proliferation. oxLDL induced Tm generated Tregs apoptosis in controls and CKD4 patients, especially in HD patients (P < 0.001, respectively). CONCLUSION: Dysregulation of CD4+ Tm cells converting into Tregs played a role in the immune defects of CKD patients, and oxLDL induced the apoptosis of Tm generating Tregs in these subjects. Larger size of sample should be investigated to confirm the findings in further studies. PMID- 24218124 TI - Stability of BUN and creatinine determinations on the Siemens Advia 1800 analyzer. AB - BACKGROUND: Serum creatinine values of patients tend to change as a result of the use of different blanks used for creatinine determinations on the Advia 1650. After upgrading the analyzer to the Advia 1800, creatinine values tended to be more reproducible. As part of a quality assurance investigation to test the reproducibilities of creatinine values, we determined serial creatinine values in the sera of 13 patients whose initial values were either in the reference range or elevated (range 0.58-7.8 mg/dl). These values were determined concurrently with serum blood urea nitrogen (BUN) determinations (range 6.0-84.4 mg/dl) as these two analytes are used together in evaluation of renal function. METHODS: We determined BUN and creatinine values, using the glutamate dehydrogenase lined enzyme assay system and the Jaffe method, respectively. RESULTS: We find that all values for creatinine on samples stored at 4 degrees C were reproducible as were the corresponding BUN values, which is revealed by low values for the coefficients of variation (CVs), that is, mean CV of 4.55% for creatinine and 2.52% for BUN. One sample with relatively high CV (10.6%) for creatinine was found to have an initial value of 1.1 mg/dl, in the reference range; but, on repeat determinations, the obtained levels were as high as 1.5 mg/dl, above the reference range. BUN values for this sample remained in the reference range, suggesting that no renal disease was present. CONCLUSION: We conclude that creatinine and BUN determinations are stable, but occasional spurious creatinine values can occur on the Advia 1800 analyzer. PMID- 24218123 TI - The association of MTHFR C677T gene variants and lipid profiles or body mass index in patients with diabetic and nondiabetic coronary heart disease. AB - BACKGROUND: The aim of this study is to investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T mutation is associated with the development of hyperlipoproteinemia and obesity in coronary heart disease (CHD). METHODS: This study was carried out in 82 diabetic and 112 nondiabetic patients with CHD and in 138 CHD-free healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis techniques were used to determine the MTHFR C677T. RESULTS: Distributions of MTHFR genotypes (C677T dbSNP: rs1801133) were similar in our study groups (P > 0.05). There was no statistical association between biochemical parameters and genotype distribution in nondiabetic CHD patients, while diabetic CC genotype carriers have elevated levels of body mass index (BMI) independently from lipid profiles (P = 0.002). In diabetic CHD patients, while evaluating the clinical parameters according to gender, it was found that gender had an impact on BMI (P = 0.013). Due to this gender effect, a multivariate analysis was conducted on the diabetic CHD patient group. The multivariate logistic regression analysis confirmed that the MTHFR-CC genotype was associated with elevated BMI levels in diabetic CHD patients (odds ratio [OR] = 5.42, P = 0.003). CONCLUSION: The results of the present study demonstrated that possessing T allele of MTHFR C677T mutation indicates a protective association on BMI independently from other risk factors. PMID- 24218125 TI - Biological variations of some analytes in renal posttransplant patients: a different way to assess routine parameters. AB - BACKGROUND: Biological variation (BV) data of analytes have been used to evaluate the significant changes in serial results (reference change value, RCV) of healthy individuals in clinical laboratories. However, BV data of healthy subjects may not be identical to the analytes of patients with ongoing clinical condition. The aim of this study was to calculate intra-(CVw) (coefficient of variation for intra-individual BV) and inter-individual (CVg) BV, index of individuality, and RCV of nine serum analytes of renal posttransplant patients. METHODS: Six serum specimens were obtained in an interval of two months in a one year period from 70 transplant patients who had been stable for three years. Each time creatinine, uric acid, urea, sodium, potassium, calcium, inorganic phosphate, total protein, and albumin of these patients were analyzed with an integrated clinical chemistry/immunoassay auto-analyzer. ANOVA tests were used to calculate the variations. Results were compared with the data of healthy subjects obtained from BV database. RESULTS: CVw of all nine analytes of the renal transplant patients were higher than the healthy subjects. RCVs of these analytes were calculated as 14.5% for creatinine, 16.5% for urea, 13.7% for urate, 12.57% for albumin, 8.26% for total protein, 3.25% for sodium, 12.81% for potassium, 5.88% for calcium, and 21.57% for inorganic phosphate. CONCLUSION: RCV concept for predicting the clinical status in posttransplant population represents an optimization of laboratory reporting and could be a valuable tool for clinical decision. PMID- 24218126 TI - Risk for early pregnancy loss by factor XIII Val34Leu: the impact of fibrinogen concentration. AB - BACKGROUND: We have already described a significantly elevated overall risk for recurrent pregnancy loss (RPL) in women carrying the coagulation factor XIII (FXIII) Val34Leu and/or the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism assuming that these polymorphisms contribute synergistically to RPL because of impaired hypofibrinolysis. Recent studies on FXIII indicate that the impact of the FXIII 34Leu genotype on fibrin structure and fibrinolysis is affected by fibrinogen concentration. Therefore, we reinvestigated the association between fibrinogen concentrations and FXIII Val34Leu with early RPL. MATERIALS AND METHODS: In this case-control study, we enrolled 49 women with a history of two consecutive or three to six nonconsecutive pregnancy losses between the 8th and 12th week of gestation and 48 healthy controls. The risk for RPL in carriers of FXIII 34Leu at fibrinogen levels above or below the median and first tertile of controls was evaluated. RESULTS: In carriers of the 34Leu allele, fibrinogen levels below the median (i.e., <= 300 mg/dl) and the first tertile (i.e., <= 284 mg/dl) of controls were associated with an increased risk for RPL [(2.9 (1.1-7.7), 3.9(1.0-15.0)]. CONCLUSIONS: The FXIII Val34Leu polymorphism may be associated with the development of early RPL in association with fibrinogen concentrations. At fibrinogen levels in the low normal range, FXIII 34Leu may modify fibrin structure toward an increased resistance to fibrinolysis. PMID- 24218127 TI - A one-step RT-PCR array for detection and differentiation of zoonotic influenza viruses H5N1, H9N2, and H1N1. AB - BACKGROUND: Rapid and comprehensive pathogen identification is crucial in zoonotic influenza diagnosis. METHODS: By optimizing the design of primers and probes and reverse-transcriptase polymerase chain reaction (RT-PCR) conditions, we achieved simultaneous detection of multiple influenza and zoonotic influenza viruses, including H1N1, H5N1, and H9N2 strains, in a one-step, quantitative real time RT-PCR array (rRT-PCR array) of RNA from multiple influenza strains utilizing a single set of conditions for RT-PCR amplification. The target sequences from all targeted zoonotic influenza viruses were cloned into recombinant RNA virus particles, which were used to evaluate sensitivity, specificity, and reproducibility of the zoonotic influenza viruses RT-PCR array. RESULTS: The detection limit of the array was shown to be between 10(0) and 10(1) copies per reaction, and the standard curve demonstrated a linear range from 10 to 10(6) copies. Thus, the analytical sensitivity of this zoonotic influenza viruses RT-PCR array is 10-100 times higher than conventional RT-PCR. Specificity of the one-step zoonotic influenza viruses RT-PCR array was verified by comparison of results obtained with retroviral-like particles (RVPs), which contained RNA from isolates of seasonal influenza viruses, zoonotic influenza viruses, and other pathogens known to cause acute respiratory disease. CONCLUSION: The high sensitivity, rapidity, reproducibility, and specificity of this zoonotic influenza viruses rRT-PCR array has been verified as being sufficient to detect the presence of multiple zoonotic influenza viruses in a single assay. The zoonotic influenza viruses RT-PCR array might provide rapid identification of emergent zoonotic influenza viruses strains during influenza outbreaks and disease surveillance initiatives. PMID- 24218128 TI - Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients? AB - BACKGROUND: The aim of the study was to determine the clinical usefulness of N terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor. PMID- 24218129 TI - An improved method on isolation and serial passage of Chlamydia pneumoniae from human peripheral blood mononuclear cells. AB - BACKGROUND: Conventional method for Chlamydia pneumoniae (Cpn) isolation and propagation is technically challenging and time-consuming. Here, we developed a method to improve the isolation and passage of Cpn collected from human peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs positive with Cpn antigen (Cpn-Ag) were isolated, then centrifuged and cultured with Hep-2 cells after being broken. Cells were broken again and put into new Hep-2 cells to finish totally four passages with isolated and imported Cpn. Microimmunofluorescence method was used to detect Cpn. Inclusion forming unit (IFU) number was counted for each passage. Polymerase chain reaction (PCR) method was used to detect Cpn DNA. Efficiency of different centrifugation modes was compared. RESULTS: Hep-2 cells of the first and second passages were strong positive with Cpn-Ag, the third passage was positive, and the fourth negative. Degeneration appeared in the fourth passage for isolated Cpn and third passage for imported strain. Centrifugation mode of 1,000 rpm for 2 h was the most efficient for Cpn propagation and passage. CONCLUSION: This simplified method achieved efficient isolation, propagation, and passage of Cpn from PBMCs, and isolated strain was superior to imported strain on propagating ability. PMID- 24218130 TI - Comparative evaluation of a new chemiluminiscent assay and an ELISA for the detection of IgM against measles. AB - BACKGROUND: The primary test for the laboratory confirmation of measles is immunoglobulin M (IgM) serology. It is therefore important to evaluate new commercial measles IgM immunoassays to ensure high-quality measles diagnostic testing. The purpose of this study was to evaluate the diagnostic performance of LIAISON IgM measles (DiaSorin, Saluggia, Italy), a new automated chemiluminescence immunoassay (CLIA), in comparison with enzyme immunoassay (EIA) Enzygnost (Siemens, Marburg, Germany). METHODS: Sensitivity was examined using a panel of measles laboratory confirmed sera; specificity was addressed by testing sera from healthy populations and subjects with infections that may interfere with measles IgM serology. RESULTS: The diagnostic performances of the two assays were very similar: both Enzygnost EIA and LIAISON CLIA performed with a sensitivity of 93.7% and 98.8%, whereas the specificity was 96.8% and 97.9%, respectively. CONCLUSION: We concluded that LIAISON IgM measles can be a good alternative to the other immunoassay for laboratory measles confirmation. PMID- 24218131 TI - Differential diagnostics of Thalassemia Minor by artificial neural networks model. AB - BACKGROUND: Current methods used to diagnose the thalassemia minor (TM) patients require high-cost assays, while broader screening based on routine blood count has limited specificity and sensitivity. This study developed a new screening technique for TM patients' diagnosis. METHODS: The study enrolled 526 patients database that included 185 verified alpha and beta TM cases, and control group consisted of iron-deficiency anemia (IDA), myelodysplastic syndrome (MDS), and healthy patients. More than 1,500 artificial neural networks (ANNs) models were created and the networks that gave high accuracy were selected for the study. TM patients were identified from the general database using the best-optimized ANNs. RESULTS: Comparison between three or six routine blood count parameters determined a slightly higher accuracy of the model with the three-parameter scheme, including mean corpuscular volume, red blood cell distribution width, and red blood cell. Based on these parameters, we were able to separate TM patients from the control group and MDS group, with specificity of 0.967 and sensitivity of 1. Including IDA patients into comparison gave lower but, still, very good values of specificity of 0.968 and sensitivity of 0.9. CONCLUSION: ANN-based TM diagnostics should be used for broad automatic screening of general population prior diagnosis with high-cost tests. PMID- 24218132 TI - Optimization of PCR conditions for amplification of GC-Rich EGFR promoter sequence. AB - BACKGROUND: Polymerase chain reaction (PCR) is an extremely sensitive method that often demands optimization, especially when difficult templates need to be amplified. The aim of the present study was to optimize the PCR conditions for amplification of the epidermal growth factor receptor (EGFR) promoter sequence featuring an extremely high guanine-cytosine (GC) content in order to detect single nucleotide polymorphisms -216G>T and -191C>A. METHODS: Genomic DNA used for amplification was extracted from formalin-fixed paraffin-embedded lung tumor tissue and PCR products were detected by agarose gel electrophoresis. RESULTS: Results showed that addition of 5% dimethyl sulfoxide (DMSO), as well as DNA concentration in PCR reaction of at least 2 MUg/ml, were necessary for successful amplification. Due to high GC content, optimal annealing temperature was 7 degrees C higher than calculated, while adequate MgCl2 concentration ranged from 1.5 to 2.0 mM. CONCLUSION: In conclusion, EGFR promoter region is a difficult PCR target, but it could be amplified after optimization of MgCl2 concentration and annealing temperature in the presence of DMSO and the DNA template of acceptable concentration. PMID- 24218133 TI - Oxidative stress-related enzyme polymorphisms associated with the immunological biomarkers levels in heavy drinkers in Taiwan. AB - BACKGROUND: Excessive alcohol intake can result in the oxidative stress in cells and the genetic variations of alcohol-metabolizing enzymes are responsible for the different degrees of toxicity of alcohol in several organs, such as the liver and immunological systems. We hypothesized that the alteration of oxidative stress due to some genetic variations of oxidative stress-related enzymes could result in changes of specific biomarkers, and heavy drinkers could be cautioned about the predictive likelihood to induce drinking-induced diseases. METHODS: A total of 108 heavy drinkers and 106 nonheavy drinkers were enrolled and the hematological, biochemical, and immunological tests were measured; the genotypes of oxidative stress-related enzymes, including manganese superoxide dismutase (MnSOD1183T>C), glutathione peroxidase 1 (GPX1Pro198Leu), catalase (CAT-262C>T), and myeloperoxidase (MPO-463G>A), were assayed by real-time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: For the males, the levels of carbohydrate-deficient transferrin (CDT), malondialdehyde (MDA), CD4(+), immunoglobulin G (IgG), immunoglobulin M (IgM), and IL-6 were significantly different between the two groups. Furthermore, there were higher proportions of CD19(+) cells and lower TNF-alpha levels in heavy drinkers with the MnSOD C carriers, and there were higher percentages of CD19(+) cells and IL-6 levels in heavy drinkers with the combined genotypes of MnSOD C carriers and MPO A carriers. CONCLUSIONS: Our findings indicate that heavy drinkers may be cautioned predictive likelihood for them to induce drinking induced diseases by analyzing their MnSOD genotypes and immunological biomarkers. PMID- 24218134 TI - Hepcidin-25 concentrations are markedly increased in patients with chronic kidney disease and are inversely correlated with estimated glomerular filtration rates. AB - BACKGROUND: Hepcidin-25 regulates iron homeostasis by binding the iron transporter ferroportin, causing its degradation. Increased hepcidin-25 causes decreased intestinal iron absorption and release from intracellular stores. Our objective in this study was to measure hepcidin-25 levels in patients with chronic kidney disease (CKD) to determine if they might contribute to the anemia of CKD. METHODS: We used a hepcidin-25-specific enzyme-linked immunosorbent assay to measure hepcidin-25 in 103 CKD patients and 100 healthy individuals. We assessed in CKD subjects the correlation of hepcidin-25 with creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, blood urea nitrogen, serum iron, transferrin, and ferritin. RESULTS: Hepcidin-25 concentrations in CKD patients were significantly increased compared to healthy subjects (60.4 +/- 6.1 MUg/l vs. 3.0 +/- 0.5 MUg/l, P < 0.001). Hepcidin-25 concentrations were directly correlated with creatinine (R = 0.28, P = 0.004) and inversely correlated with eGFR (R = -0.32, P = 0.001). Hepcidin-25 levels were also correlated with transferrin (R = -0.28, P = 0.004) and ferritin (R = 0.80, P < 0.001). CONCLUSION: The direct correlation of hepcidin-25 with creatinine and its inverse correlation with eGFR suggest that hepcidin-25 levels increase as renal function deteriorates, possibly due to decreased hepcidin-25 renal clearance. PMID- 24218135 TI - How to include informal care in economic evaluations. AB - Economic evaluations of health interventions aim to support decision making in healthcare. To effectively do so, evaluations need to include all relevant costs and effects of an intervention. Informal care provided by family or friends is an important element of care for many patients, but can have a profound impact on the health and well-being of carers. Therefore, informal care should be considered in economic evaluations of health interventions. Different methods to do so exist. This paper provides an overview of state-of-the-art methods available for this purpose, illustrated with practical examples. Since the choice of measurement and valuation technique depends on the type and perspective of the economic evaluation, this paper supports researchers in choosing the appropriate techniques to include informal care in their economic evaluation of a health intervention. We discuss the different approaches to measuring and valuing informal care, covering both partial and full valuation methods, allowing inclusion as costs or effects. PMID- 24218136 TI - Selective MAO-B inhibitors: a lesson from natural products. AB - Monoamine oxidases (MAOs) are mitochondrial bound enzymes, which catalyze the oxidative deamination of monoamine neurotransmitters. Inside the brain, MAOs are present in two isoforms: MAO-A and MAO-B. The activity of MAO-B is generally higher in patients affected by neurodegenerative diseases like Alzheimer's and Parkinson's. Therefore, the search for potent and selective MAO-B inhibitors is still a challenge for medicinal chemists. Nature has always been a source of inspiration for the discovery of new lead compounds. Moreover, natural medicine is a major component in all traditional medicine systems. In this review, we present the latest discoveries in the search for selective MAO-B inhibitors from natural sources. For clarity, compounds have been classified on the basis of structural analogy or source: flavonoids, xanthones, tannins, proanthocyanidins, iridoid glucosides, curcumin, alkaloids, cannabinoids, and natural sources extracts. MAO inhibition values reported in the text are not always consistent due to the high variability of MAO sources (bovine, pig, rat brain or liver, and human) and to the heterogeneity of the experimental protocols used. PMID- 24218137 TI - The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. AB - The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE(+) GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE(+) GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE(+) GC cells, whereas sequential switching gives rise to IgE(+) PCs. We propose a comprehensive model for the generation and memory of IgE responses. PMID- 24218138 TI - Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells. AB - Long-lived antibody memory is mediated by the combined effects of long-lived plasma cells (PCs) and memory B cells generated in response to T cell-dependent antigens (Ags). IL-10 and IL-21 can activate multiple signaling pathways, including STAT1, STAT3, and STAT5; ERK; PI3K/Akt, and potently promote human B cell differentiation. We previously showed that loss-of-function mutations in STAT3, but not STAT1, abrogate IL-10- and IL-21-mediated differentiation of human naive B cells into plasmablasts. We report here that, in contrast to naive B cells, STAT3-deficient memory B cells responded to these STAT3-activating cytokines, differentiating into plasmablasts and secreting high levels of IgM, IgG, and IgA, as well as Ag-specific IgG. This was associated with the induction of the molecular machinery necessary for PC formation. Mutations in IL21R, however, abolished IL-21-induced responses of both naive and memory human B cells and compromised memory B cell formation in vivo. These findings reveal a key role for IL-21R/STAT3 signaling in regulating human B cell function. Furthermore, our results indicate that the threshold of STAT3 activation required for differentiation is lower in memory compared with naive B cells, thereby identifying an intrinsic difference in the mechanism underlying differentiation of naive versus memory B cells. PMID- 24218139 TI - Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders. AB - Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcytosine dioxygenase 2 (TET2) mutations. Consistent with these findings, deletion of Ezh2 alone was enough to induce MDS/MPN-like diseases in mice. Furthermore, concurrent depletion of Ezh2 and Tet2 established more advanced myelodysplasia and markedly accelerated the development of myelodysplastic disorders including both MDS and MDS/MPN. Comprehensive genome wide analyses in hematopoietic progenitor cells revealed that upon deletion of Ezh2, key developmental regulator genes were kept transcriptionally repressed, suggesting compensation by Ezh1, whereas a cohort of oncogenic direct and indirect polycomb targets became derepressed. Our findings provide the first evidence of the tumor suppressor function of EZH2 in myeloid malignancies and highlight the cooperative effect of concurrent gene mutations in the pathogenesis of myelodysplastic disorders. PMID- 24218141 TI - Ethical considerations when employing fake identities in online social networks for research. AB - Online social networks (OSNs) have rapidly become a prominent and widely used service, offering a wealth of personal and sensitive information with significant security and privacy implications. Hence, OSNs are also an important--and popular -subject for research. To perform research based on real-life evidence, however, researchers may need to access OSN data, such as texts and files uploaded by users and connections among users. This raises significant ethical problems. Currently, there are no clear ethical guidelines, and researchers may end up (unintentionally) performing ethically questionable research, sometimes even when more ethical research alternatives exist. For example, several studies have employed "fake identities" to collect data from OSNs, but fake identities may be used for attacks and are considered a security issue. Is it legitimate to use fake identities for studying OSNs or for collecting OSN data for research? We present a taxonomy of the ethical challenges facing researchers of OSNs and compare different approaches. We demonstrate how ethical considerations have been taken into account in previous studies that used fake identities. In addition, several possible approaches are offered to reduce or avoid ethical misconducts. We hope this work will stimulate the development and use of ethical practices and methods in the research of online social networks. PMID- 24218140 TI - Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. AB - Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10-30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis. PMID- 24218142 TI - Explicit training in human values and social attitudes of future engineers in Spain : commentary on "preparing to understand and use science in the real world: interdisciplinary study concentrations at the technical University of Darmstadt". AB - In Spain before the 1990s there was no clear and explicit comprehensive training for future engineers with regard to social responsibility and social commitment. Following the Spanish university curricular reform, which began in the early 1990s, a number of optional subjects became available to students, concerning science, technology and society (STS), international cooperation, the environment and sustainability. The latest redefinition of the Spanish curriculum in line with the Bologna agreements has reduced the number of non-obligatory subjects, but could lead to improving preparation for social responsibility due to the requirement that the design of curricula and the assessment of students should be based on competencies, some of which include human values and attitudes. PMID- 24218143 TI - Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation. AB - Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant syndrome. Although thymic carcinoid tumor is recognized as a part of MEN1 syndrome but functioning thymic carcinoid tumor as the first presentation of the MEN1 seems to be very rare. In this report, we present a 29-year-old male who developed ectopic Cushing syndrome secondary to thymic carcinoid tumor and was diagnosed as MEN1 syndrome 2 years later. Further evaluation revealed the presence of carcinoid tumor and other MEN 1 manifestations in several other member of family. Genetic evaluation showed presence of a previously reported mutation in exon 10(R527X) of MEN1 gene in these patients. This presentation showed that thymic neuroendocrine tumor could be the first manifestation of the MEN1 syndrome and it might be diagnosed as a dominant manifestation of this syndrome in a family. We suggest biochemical or genetic screening for MEN-1 syndrome for patients with thymic carcinoid. PMID- 24218145 TI - Translating Falls Prevention Knowledge to Community-Dwelling Older PLWD: A Mixed Method Systematic Review. AB - PURPOSE OF THE STUDY: Falls prevention evidence is strong, but little is known about uptake of strategies for people living with dementia (PLWD). This mixed method systematic review aimed to integrate evidence of falls prevention efficacy with views/experiences of PLWD. DESIGN AND METHODS: Eight electronic databases were searched. Inclusion criteria included quantitative or qualitative studies examining knowledge translation of falls prevention strategies in community dwelling PLWD and/or their caregiver. Study quality was assessed, and findings are narratively described. RESULTS: Six quantitative and five qualitative studies were included. Study quality was mixed. Quantitative studies showed limited evidence of effectiveness on reduction in falls risk, falls and hospitalization rates, nursing home admission, decline in activities of daily living, and adherence to strategies. Qualitative themes showed inclusion of caregiver and health professionals as key to program success, but many factors influence participation. IMPLICATIONS: Synthesizing the findings generated a new understanding of falls prevention for this high-risk group. A focus upon health professional and caregiver involvement and accommodation of individual preferences may result in increased engagement with falls prevention strategies. PMID- 24218144 TI - A tandem isomerization/prins strategy: iridium(III)/Bronsted acid cooperative catalysis. AB - Working together: A mild and efficient isomerization/protonation sequence generates pyran-fused indoles by cooperative catalysis between cationic iridium(III) and Bi(OTf)3 . Three distinct cyclization manifolds lead to the corresponding bioactive scaffolds in good yields. In addition, N-substituted indoles can be synthesized enantioselectively in the presence of a chiral phosphate. PMID- 24218146 TI - The role of organizational culture in retaining nursing workforce. AB - PURPOSE OF THE STUDY: We examined how organizational culture in nursing homes affects staff turnover, because culture is a first step to creating satisfactory work environments. DESIGN AND METHODS: Nursing home administrators were asked in 2009 to report on facility culture and staff turnover. We received responses from 419 of 1,056 administrators contacted. Respondents reported the strength of cultural values using scales from a Competing Values Framework and percent of staff leaving annually for Registered Nurse (RN), Licensed Practice Nurse (LPN), and nursing aide (NA) staff. We estimated negative binomial models predicting turnover. RESULTS: Turnover rates are lower than found in past but remain significantly higher among NAs than among RNs or LPNs. Facilities with stronger market values had increased turnover among RNs and LPNs, and among NAs when turnover was adjusted for facilities with few staff. Facilities emphasizing hierarchical internal processes had lower RN turnover. Group and developmental values focusing on staff and innovation only lowered LPN turnover. Finally, effects on NA turnover become insignificant when turnover was adjusted if voluntary turnover was reported. IMPLICATIONS: Organizational culture had differential effects on the turnover of RN, LPN, and NA staff that should be addressed in developing culture-change strategies. More flexible organizational culture values were important for LPN staff only, whereas unexpectedly, greater emphasis on rigid internal rules helped facilities retain RNs. Facilities with a stronger focus on customer needs had higher turnover among all staff. PMID- 24218147 TI - Perinatal exposure to BDE-99 causes decreased protein levels of cyclin D1 via GSK3beta activation and increased ROS production in rat pup livers. AB - We here examined the potential liver toxicity in rat pups from dams exposed during the gestational and lactation periods to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Dams were exposed to 0, 1, and 2mg/kg/day of BDE-99 from gestation day 6 to postnatal day 21. When the pups were weaning, the liver from 1 pup of each litter was excised to evaluate oxidative stress markers and the messenger RNA (mRNA) expression of multiple cytochrome P450 (CYP) isoforms. To determine whether thyroid hormone (TH) was disrupted, the protein and mRNA expressions of several TH receptor (TR) isoforms, as well as the protein levels of cyclin D1 and the phosphorylated protein kinases Akt and glycogen synthase kinase 3 beta (GSK3beta), were evaluated. Perinatal exposure to BDE-99 produced decreased levels of cyclin D1 in rat pup livers. A decrease in the active form of Akt and an increase in the active form of GSK3beta were observed. The decreased Akt pathway may be due to a potential disruption of the nongenomic actions of TH by BDE-99 and its metabolites. This possible TH disruption was noted as a decrease in TR isoforms expression. By contrast, we observed an upregulation of CYP2B1 gene expression, which is correlated with an increase in reactive oxygen species production. This outcome indicates activation of the nuclear constitutive androstane receptor, which could induce the expression of other enzymes capable of metabolizing TH. The present findings support the hypothesis that perinatal exposure to PBDEs, at levels found in humans, may have serious implications for metabolic processes in rat pup livers. PMID- 24218148 TI - Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury. AB - Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia inducible factors (HIFs). Previous work revealed that though HIF1alpha contrib utes to cobalt toxicity in vitro, loss of HIF1alpha in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1alpha and HIF2alpha show unique tissue expression profiles, and HIF2alpha is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2alpha activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2alpha in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2alpha-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2alpha(Delta/Delta)) were exposed to cobalt (60 ug/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2alpha leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2alpha(Delta/Delta) mice, suggesting a role for epithelial HIF2alpha in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2alpha(Delta/Delta) and control mice were compared. In summary, our data suggest that although loss of HIF2alpha does not afford protection from cobalt induced lung inflammation, epithelial HIF2alpha signaling does play an important role in modulating the inflammatory and repair response in the lung. PMID- 24218149 TI - Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy. AB - Adverse intrauterine environments have been associated with increased risk of later cardiovascular disease and hypertension. In an animal model using diverse developmental toxicants, we measured blood pressure (BP), renal nephron endowment, renal glucocorticoid receptor (GR) gene expression, and serum aldosterone in offspring of pregnant Sprague Dawley rats exposed to dexamethasone (Dex), perfluorooctane sulfonate (PFOS), atrazine, perfluorononanoic acid (PFNA), arsenic, or nicotine. BP was assessed by tail cuff photoplethysmography, nephron endowment by confocal microscopy, and renal GR mRNA by qPCR. BP was also measured by telemetry, and corticosterone (CORT) was measured in resting or restrained Dex and atrazine offspring. Treated dams gained less weight during treatment in all groups except arsenic. There were chemical- and sex-specific effects on birth weight, but offspring body weights were similar by weaning. BP was higher in Dex, PFOS, atrazine, and PFNA male offspring by 7-10 weeks. Female offspring exhibited elevated BP at 10 weeks for PFNA and arsenic, and at 37 weeks for Dex, PFOS, and atrazine. Dex, PFOS, and atrazine offspring still exhibited elevated BP at 52-65 weeks of age; others did not. Elevated BP was associated with lower nephron counts. Dex, PFOS, and atrazine offspring had elevated renal GR gene expression. Elevations in BP were also observed in Dex and atrazine offspring by radiotelemetry. Atrazine offspring exhibited enhanced CORT response to restraint. Elevated offspring BP was induced by maternal exposure to toxicants. Because all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations. PMID- 24218151 TI - Sustained release of naltrexone from poly(n-isopropylacrylamide) microgels. AB - The release of the opioid antagonist naltrexone from neutral poly(N isopropylacrylamide) (PNIPAAM) microgels and negatively charged PNIPAAM microgels containing acrylic acid groups (PNIPAAM-co-PAA) has been studied at various microgel and drug concentrations. The release curves were found to be well represented by the Weibull equation. The release rates were observed to be dependent on the microgel concentration. At most conditions, the release from the charged microgels was slower than for the neutral microgels. In addition, the charged microgels exhibited a release lag time, which was dependent on the microgel concentration. No significant lag time could be observed for the neutral microgels. Increasing the naltrexone concentration did not significantly affect the release rates from the neutral microgels, but the release from the charged microgels became faster. The microgels did not exhibit any significant cytotoxic effect on HeLa cells at the tested concentrations. PMID- 24218150 TI - Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes. AB - Polybrominated diphenyl ether BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is a thyroid hormone disruptor in mice; hepatic induction of various metabolic enzymes and transporters has been suggested as the mechanism for this disruption. Utilizing Car (-/-) and Pxr (-/-) mice as well as human primary hepatocytes, here we have demonstrated that BDE-47 activated both mouse and human nuclear receptor constitutive activated/androstane receptor (CAR). In mouse livers, CAR, not PXR, was responsible for Cyp2b10 mRNA induction by BDE-47. In human primary hepatocytes, BDE-47 was able to induce translocation of YFP-tagged human CAR from the cytoplasm to the nucleus andCYP2B6 and CYP3A4 mRNAs expressions. BDE-47 activated human CAR in a manner akin to the human CAR ligand CITCO (6-(4 Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4 dichlorobenzyl)oxime) in luciferase-reporter assays using Huh-7 cells. In contrast, mouse CAR was not potently activated by BDE-47 in the same reporter assays. Furthermore, human pregnane X receptor (PXR) was effectively activated by BDE-47 while mouse PXR was weakly activated in luciferase-reporter assays. Our results indicate that BDE-47 induces CYP genes through activation of human CAR in addition to the previously identified pathway through human PXR. PMID- 24218152 TI - Orthopedic surgery in the developing world: workforce and operative volumes in Ghana compared to those in the United States. AB - BACKGROUND: Musculoskeletal disease is a growing burden in low- and middle-income countries (LMICs), yet little research exists to describe the problem. The purposes of this study were to characterize orthopedic surgery in an LMIC and compare the findings to those from a developed country. METHODS: The study location was the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. Orthopedic surgeon, resident, and postgraduate training program numbers were compared to analogous data from a developed nation, the United States. Annual surgical volumes were compared to those at a level I trauma center in the United States, the San Francisco General Hospital (SFGH). RESULTS: There were 24 surgeons in Ghana compared to 23,956 in the United States. There were 7 orthopedic residents and 1 residency program in Ghana versus 3,371 residents and 155 residencies in the United States. Annual case volume was 2,161 at KATH and 2,132 at SFGH. Trauma accounted for 95 % of operations at KATH compared to 65 % at SFGH. The proportion of surgeries devoted to severe fractures was 29 % at KATH compared to 12 % at SFGH. Infections comprised 15 % of procedures at KATH and 5 % at SFGH. CONCLUSIONS: Annual case volume at a referral hospital in an LMIC is equivalent to that of a level I trauma center in an industrialized country. Total case volume is similar, but the LMIC institution manages a disproportionately large number of trauma cases, severe fractures, and infections. There is a large burden of orthopedic disease in the developing nation, and there are too few providers and training programs to address these conditions. PMID- 24218153 TI - Shortage of doctors, shortage of data: a review of the global surgery, obstetrics, and anesthesia workforce literature. AB - INTRODUCTION: The global surgery workforce is in crisis in many low- and middle income countries (LMICs). The shortage of surgery, obstetrics, and anesthesia providers is an important cause of the unmet need for surgical care in LMICs. The goal of this paper is to summarize the available literature about surgical physicians in LMICs and to describe ongoing initiatives to supplement the existing surgical workforce data. METHODS: We performed a systematic search and literature review of the English-language literature regarding the number of surgeons, obstetrician-gynecologists, and anesthesiologists practicing in LMICs. RESULTS: Literature describing the number of surgeons, obstetricians, and anesthesiologists practicing in LMICs represents a small minority of LMICs, and indicates consistently low levels of surgical physicians. Our literature search yielded comprehensive data for only six countries. No national data were found for 23 of the 57 countries considered by the World Health Organization (WHO) to be in health workforce 'crisis.' Across LMICs, general surgeon density ranged from 0.13 to 1.57 per 100,000 population, obstetrician density ranged from 0.042 to 12.5 per 100,000, and anesthesiologist density ranged from 0 to 4.9 per 100,000. Total anesthesiologist, obstetrician, and surgeon density was significantly correlated with gross domestic product (GDP) per capita (r (2) = 0.097, p = 0.0002). CONCLUSION: The global surgery workforce is in crisis, yet is poorly characterized by the current English-language literature. There is a critical need for systematically collected, national-level data regarding surgery providers in LMICs to guide improvements in surgery access and care. The Harvard Global Surgery Workforce Initiative and the WHO global surgical workforce database are working to address this need by surveying Ministries of Health and surgical professional organizations around the world. PMID- 24218155 TI - A role for the polarity complex and PI3 kinase in branch formation within retinotectal arbors of zebrafish. AB - The developing zebrafish retinotectal arbors make many trial branches with synapses but most are retracted. With NMDA blockers, branches are withdrawn at a higher rate, and a synapse on a branch not only stabilizes that branch, but biases new branches to form nearby. Here, we tested whether new branch formation requires the polarity complex, which is essential for organizing the cytoskeleton in initial axon formation. The complex (PAR3, PAR6, and atypical protein kinase C [aPKC]) is downstream of phosphatidyl-inositol-3-kinase (PI3K), and its aPKC could be activated by retrograde arachidonic acid synaptic signaling. DiO-labeled arbors in zebrafish were imaged on day 3 (before treatment) and 1-2 days after treatment to suppress or inhibit PAR3, PAR6, or PI3K. Intraocular antisense (AS) oligos to PAR3 or PAR6 both severely limited branch addition, which was most evident in arbors with few branches before treatment. As a result of the inability to branch, arbor segments grew longer than in controls. Both PI3K inhibition (LY294002) and AS suppression of PI3Kalpha and PI3Kdelta isoforms likewise limited branch addition but also decreased growth, as the sum of segment lengths was below normal after 2 days. Both the results support the idea that the polarity complex and PI3K participate in arbor branch formation. The PKC inhibitor Go6983 also severely restricted branch addition and growth, as did bisindolyl-maleimide and calphostin C reported previously, consistent with PKCzeta, but not PKCu, participation. These experiments suggest a mechanism whereby activity signaling could affect the branching of retinotectal arbors. PMID- 24218156 TI - Normative data for measuring performance change on parallel forms of a 15-word list recall test. AB - Declarative memory evaluation is an essential step in the clinical and neuropsychological assessment of a variety of neurological disorders. It typically addresses the issue of normality/abnormality of an individual's performance. Another clinical application of the neuropsychological assessment of declarative memory is the longitudinal evaluation of an individual's performance change. In fact, in a variety of neurological conditions repeated assessments are needed to evaluate the modifications of a memory disorder as a function of time or in response to a pharmacological or rehabilitation treatment. This study was aimed at collecting data for measuring and interpreting performance change on a memory test for verbal material. For this purpose, we administered to 100 healthy subjects (age range 20-80 years; years of formal education range 8-17 years) three parallel forms of a test requiring the immediate and delayed recall of a 15 word list. The subjects performed the recall test three times (each time with a different list) at least 1 week apart. The order of the lists was randomized across subjects. Results revealed that performance on the three lists was highly correlated and did not vary as a function of the order of presentation. However, accuracy of recall was slightly better on a list compared to the others. Based on a method devised by Payne and Jones (J Clin Psychol 13:115-121, 1957), we provide normative data for establishing whether a discrepancy in recall accuracy on two versions of the test exceeds the discrepancy expected based on the performance of normal controls. PMID- 24218157 TI - Comment on "Mechanism of Pt(IV) sonochemical reduction in formic acid media and pure water". PMID- 24218158 TI - Impact of hypertension history on short and long-term prognosis in patients with acute myocardial infarction treated with percutaneous angioplasty: comparison between STEMI and NSTEMI. AB - Previous studies analyzing the impact of hypertension (HTN) on myocardial infarction (MI) outcome reached conflicting results and scarce data are available in patients treated with percutaneous coronary intervention (PCI). In this study the prognostic impact of HTN history in ST-elevation MI (STEMI) and Non-STEMI (NSTEMI) patients treated with PCI was analyzed. We compared characteristics of 1,031 STEMI and 437 NSTEMI patients, in relation to the presence of HTN. Median follow-up duration was 40.2 months. HTN was significantly higher in NSTEMI vs. STEMI patients (p < 0.001). NSTEMI patients were older, with higher values of left ventricular ejection fraction (LVEF) and more frequently with previous myocardial revascularization than STEMI patients either among hypertensives and non-hypertensives. At univariate analysis HTN resulted associated with long-term mortality in STEMI but not in NSTEMI patients. At multivariate analysis HTN was not associated with either in-hospital and long-term mortality in both NSTEMI and STEMI group. In conclusion, in the PCI era HTN does not influence MI patients prognosis; other factors, such as age, admission LVEF, coronary disease extension, previous MI and creatinine levels are independently associated with MI patients outcome even though this should not discourage from a strict control of HTN after the acute event. PMID- 24218159 TI - Intramolecular polar [4(?)+2] cycloadditions of aryl-1-aza-2-azoniaallene salts: unprecedented reactivity leading to polycyclic protonated azomethine imines. PMID- 24218161 TI - The patient protection and Affordable Care Act: better coverage, worse access. Will it really improve patient safety? PMID- 24218160 TI - Stability and trunnion wear potential in large-diameter metal-on-metal total hips: a finite element analysis. AB - BACKGROUND: Large-diameter femoral heads for metal-on-metal THA hold theoretical advantages of joint stability and low bearing surface wear. However, recent reports have indicated an unacceptably high rate of wear-associated failure with large-diameter bearings, possibly due in part to increased wear at the trunnion interface. Thus, the deleterious consequences of using large heads may outweigh their theoretical advantages. QUESTIONS/PURPOSES: We investigated (1) to what extent femoral head size influenced stability in THA for several dislocation prone motions; and the biomechanics of wear at the trunnion interface by considering the relationship between (2) wear potential and head size and (3) wear potential and other factors, including cup orientation, type of hip motion, and assembly/impaction load. METHODS: Computational simulations were executed using a previously validated nonlinear contact finite element model. Stability was determined at 36 cup orientations for five distinct dislocation challenges. Wear at the trunnion interface was calculated for three separate cup orientations subjected to gait, stooping, and sit-to-stand motions. Seven head diameters were investigated: 32 to 56 mm, in 4-mm increments. RESULTS: Stability improved with increased diameter, although diminishing benefit was seen for sizes of greater than 40 mm. By contrast, contact stress and computed wear at the trunnion interface all increased unabatedly with increasing head size. Increased impaction forces resulted in only small decreases in trunnion wear generation. CONCLUSIONS: These data suggest that the theoretical advantages of large-diameter femoral heads have a limit. Diameters of greater than 40 mm demonstrated only modest improvement in terms of joint stability yet incurred substantial increase in wear potential at the trunnion. CLINICAL RELEVANCE: Our model has potential to help investigators and designers of hip implants to better understand the optimization of trunnion design for long-term durability. PMID- 24218162 TI - Cochrane in CORR(r): Viscosupplementation for the treatment of osteoarthritis of the knee. PMID- 24218163 TI - Dual plating of humeral shaft fractures: orthogonal plates biomechanically outperform side-by-side plates. AB - BACKGROUND: Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated. QUESTIONS/PURPOSES: We used finite element analysis to compare the simulated mechanical performance of five different dual small-fragment locking plate construct configurations for humeral middiaphyseal fracture fixation in terms of (1) stiffness, (2) stress shielding of bone, (3) hardware stresses, and (4) interfragmentary strain. METHODS: Middiaphyseal humeral fracture fixation was simulated using the finite element method. Three 90 degrees and two side-by-side seven-hole and nine-hole small-fragment dual locking plate configurations were tested in compression, torsion, and combined loading. The configurations chosen are based on implantation using either a posterior or anterolateral approach. RESULTS: All three of the 90 degrees configurations were more effective in restoring the intact compressive and torsional stiffness as compared with the side-by-side configurations, resulted in less stress shielding and stressed hardware, and showed interfragmentary strains between 5% to 10% in torsion and combined loading. CONCLUSIONS: The nine-hole plate anterior and seven hole plate lateral (90 degrees apart) configuration provided the best fixation. Our findings show the mechanical importance of plate placement with relation to loading in dual-plate fracture-fixation constructs. CLINICAL RELEVANCE: The results presented provide novel biomechanical information for the orthopaedic surgeon considering different treatment options for middiaphyseal humeral fractures. PMID- 24218164 TI - Expression of recombinant antibody (single chain antibody fragment) in transgenic plant Nicotiana tabacum cv. Xanthi. AB - Plants offer an alternative inexpensive and convenient technology for large scale production of recombinant proteins especially recombinant antibodies (plantibodies). In this paper, we describe the expression of a model single chain antibody fragment (B6scFv) in transgenic tobacco. Four different gene constructs of B6scFv with different target signals for expression in different compartments of a tobacco plant cell with and without endoplasmic reticulum (ER) retention signal were used. Agrobacterium mediated plant transformation of B6scFv gene was performed with tobacco leaf explants and the gene in regenerated plants was detected using histochemical GUS assay and PCR. The expression of B6scFv gene was detected by western blotting and the recombinant protein was purified from putative transgenic tobacco plants using metal affinity chromatography. The expression level of recombinant protein was determined by indirect enzyme-linked immunosorbent assay. The highest accumulation of protein was found up to 3.28 % of the total soluble protein (TSP) in plants expressing B6scFv 1003 targeted to the ER, and subsequently expression of 2.9 % of TSP in plants expressing B6scFv 1004 (with target to apoplast with ER retention signal). In contrast, lower expression of 0.78 and 0.58 % of TSP was found in plants expressing antibody fragment in cytosol and apoplast, without ER retention signal. The described method/system could be used in the future for diverse applications including expression of other recombinant molecules in plants for immunomodulation, obtaining pathogen resistance against plant pathogens, altering metabolic pathways and also for the expression of different antibodies of therapeutic and diagnostic uses. PMID- 24218166 TI - Tentative identification of sex-specific antibodies and their application for screening bovine sperm proteins for sex-specificity. AB - Our previous studies indicated that a purified rabbit antiserum against X-sperm contained sex-specific antibodies (SSAbs) which preferentially bound to sex sorted X-sperm. The specificity of sex-specific antiserum was initially demonstrated using flow cytometry only, which resulted in uncertainty. In this study, the putative SSAbs against bovine X-sperm (XSSAb) were produced by a series of immunological approaches, and the effectiveness of separation of sperm using putative XSSAb was validated. Subsequently, the XSSAb was used to immunoprecipitate sex-specific proteins (SSPs) in bovine sperm, followed by two dimensional gel electrophoresis. The results showed 7.6, 15.2 and 52.1 % of sex sorted Y-sperm, sex-sorted X-sperm and unsorted sperm were recognized by the neutralized rabbit antisera against X-sperm, respectively. Also the purity of separation of sperm using putative XSSAb reached 74.3 % when the immunologically separated sperm were injected into oocytes. In addition, three candidate SSP sports about 30 kDa were captured by the XSSAb. Our results confirmed that the putative XSSAb contained SSAbs, and implied that these three protein sports might be SSPs in bovine X-sperm. This provides a potentially more efficient method for sorting sperm and lays a foundation for future search for SSPs. PMID- 24218165 TI - Cisplatin associated with LY294002 increases cytotoxicity and induces changes in transcript profiles of glioblastoma cells. AB - Glioblastoma, one of the deadliest forms of brain tumor, responds poorly to available therapies. This highlights the intense search for new treatment approaches, and an emerging strategy is based on molecular targets. In the present work, we aimed to study whether glioblastoma cells can be sensitized by cisplatin combined with LY294002 (LY), which is an inhibitor of PI3K-related family (ATM, ATR, DNA-PK). We observed that cisplatin caused a pronounced reduction in cell proliferation in U343 and U87 cells, and LY significantly increased the cytotoxic effects caused by cisplatin under these conditions. Differently of U343, U87 cells did not show a significant induction of apoptosis. The phosphorylation level of damage response proteins was analyzed after drug treatment either with/without LY. The presence of gammaH2AX foci and phosphorylation of TP53(ser15) and CHK1(ser317) were shown in U343 cells, compatible with cisplatin-induced DNA damage. Similarly, the level of ATR phosphorylation (ser428) was also increased (24 h). The transcript expression profiles of drug-treated compared with untreated U343 cells showed significant changes in the expression of 108 genes, while 274 genes were modulated by cisplatin+LY. The combined treatment caused a high proportion of down-regulated genes, which were mainly involved with DNA repair, cell death and cell cycle control/proliferation, metabolism, transcription regulation and cellular adhesion. Altogether, the present results indicate that most probably, PI3K related kinases may play an important role in the resistance of glioblastomas cells to cisplatin, and the combination with LY can, at least in part, sensitize these cells to drug treatment. PMID- 24218167 TI - [Managing concerns about falls in older people: evaluation of the implementation of an evidence-based program]. AB - INTRODUCTION: A cognitive behavioral program reduced concerns about falling and related avoidance behavior among older community-dwelling adults in a randomized controlled trial. In the current study we examined the effects and acceptability of the program after nation-wide implementation into home care organizations in The Netherlands. METHODS: In a one-group pretest-posttest study with data collection before the start of the program and at 2 and 4 months, the effects and acceptability of the program were assessed in 125 community-dwelling older people. The outcomes of the effect evaluation included concerns about falls, related avoidance behavior, falls, fall-related medical attention, feelings of anxiety, symptoms of depression, and loneliness. RESULTS: Pretest-posttest analyses with the Wilcoxon signed-rank test and the paired t-test showed significant improvements at 4 months for concerns about falls, activity avoidance, number of falls in the past 2 months, feelings of anxiety, and symptoms of depression. No significant differences were shown for the other outcomes. DISCUSSION: After implementation in home care organizations, the outcomes indicate positive program effects on concerns about falls, avoidance behavior, and falls in community-dwelling older people. Given the similarity in results, i.e. between those of the previously performed randomized controlled trial and those of the current pretest-posttest study, we conclude that the program can be successfully implemented in practice. This article is an adjusted, Dutch version of Zijlstra GA, van Haastregt JC, Du Moulin MF, de Jonge MC, van der Poel A, Kempen GI. Effects of the implementation of an evidenc-based program to manage concerns about falls in older adults. The Gerontologist 2013;53(5):839 849; doi: 10.1093/geront/gns142. PMID- 24218168 TI - Histopathological and estrogen effect of pentachlorophenol on the rare minnow (Gobiocypris rarus). AB - Pentachlorophenol (PCP), a typical organic pollutant and environmental endocrine disruptor, has been extensively used as a pesticide and biocide worldwide. In this study, the effects of PCP on the histological and hepatic system of the rare minnow (Gobiocypris rarus) were evaluated. Vitellogenin (VTG) was used as a biomarker to evaluate the estrogen effect of PCP. The results revealed that VTG was highly expressed and PCP exposure had histopathological effects on the rare minnow. Plasma and hepatic VTG concentrations increased when female rare minnows were exposed to >=80 MUg/L PCP and male rare minnows were exposed to 40 MUg/L PCP (p < 0.05), which suggested that the VTG expression was evoked by PCP exposure. The results indicated that both plasma and liver tissue were suitable for VTG quantification. A significant decrease in the mRNA level of hepatic estrogen receptor-alpha (ERalpha) in male or juvenile was observed after exposure to >=80 or >=8 MUg/L PCP, respectively; in contrast, increased mRNA levels of ERbeta1, ERbeta2, VTGI, and VTGII in male or juvenile were detected after exposure to >=80 or >=8 MUg/L PCP, respectively. These results suggested that PCP has an estrogen effect and exists within different endocrine-disrupting pathways from other environmental contaminants. As such, VTG mRNA expression in the rare minnow may require transcription of the ERbeta1 and ERbeta2 genes. PMID- 24218169 TI - Overexpression of the Na+/K+ ATPase alpha2 but not alpha1 isoform attenuates pathological cardiac hypertrophy and remodeling. AB - RATIONALE: The Na+ / K+ ATPase (NKA) directly regulates intracellular Na+ levels, which in turn indirectly regulates Ca2+ levels by proximally controlling flux through the Na+ / Ca2+ exchanger (NCX1). Elevated Na+ levels have been reported during heart failure, which permits some degree of reverse-mode Ca2+ entry through NCX1, as well as less efficient Ca2+ clearance. OBJECTIVE: To determine whether maintaining lower intracellular Na+ levels by NKA overexpression in the heart would enhance forward-mode Ca2+ clearance and prevent reverse-mode Ca2+ entry through NCX1 to protect the heart. METHODS AND RESULTS: Cardiac-specific transgenic mice overexpressing either NKA-alpha1 or NKA-alpha2 were generated and subjected to pressure overload hypertrophic stimulation. We found that although increased expression of NKA-alpha1 had no protective effect, overexpression of NKA-alpha2 significantly decreased cardiac hypertrophy after pressure overload in mice at 2, 10, and 16 weeks of stimulation. Remarkably, total NKA protein expression and activity were not altered in either of these 2 transgenic models because increased expression of one isoform led to a concomitant decrease in the other endogenous isoform. NKA-alpha2 overexpression but not NKA-alpha1 led to significantly faster removal of bulk Ca2+ from the cytosol in a manner requiring NCX1 activity. Mechanistically, overexpressed NKA-alpha2 showed greater affinity for Na+ compared with NKA-alpha1, leading to more efficient clearance of this ion. Furthermore, overexpression of NKA-alpha2 but not NKA-alpha1 was coupled to a decrease in phospholemman expression and phosphorylation, which would favor greater NKA activity, NCX1 activity, and Ca2+ removal. CONCLUSIONS: Our results suggest that the protective effect produced by increased expression of NKA-alpha2 on the heart after pressure overload is due to more efficient Ca2+ clearance because this isoform of NKA preferentially enhances NCX1 activity compared with NKA-alpha1. PMID- 24218170 TI - Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia. AB - RATIONALE: The impact of severe cardiovascular disease and critical limb ischemia (CLI) on the bone marrow (BM) is largely unknown. OBJECTIVE: To investigate microvascular and neuropathic changes in BM of patients with CLI. METHODS AND RESULTS: BM biopsies were obtained from patients with CLI (n=33) included in the Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial (NCT00371371) and controls (n=12). We performed immunohistochemistry and histomorphometry of the BM to assess microvascular density and to evaluate pan-neuronal and sympathetic innervation, which is involved in progenitor cell mobilization. Microvascular density was reduced significantly in CLI compared with controls (P=0.01), as was sympathetic (P=0.047) and pan-neuronal innervation (P=0.006). No differences in microvascular density and sympathetic or pan-neuronal innervation were observed between patients with CLI with and without diabetes mellitus. CONCLUSIONS: CLI is associated with BM microvascular and neuropathic changes, both in patients with and without diabetes mellitus. PMID- 24218171 TI - Reduced white matter microstructural integrity correlates with cognitive deficits in minimal hepatic encephalopathy. PMID- 24218172 TI - Cardiovascular and Interventional Radiological Society of Europe (CIRSE) position statement on renal denervation for resistant hypertension. PMID- 24218173 TI - Stent-assisted coil embolization for the treatment of ruptured aneurysms at the anterior circulation: comparison between HydroSoft coils and bare platinum coils. AB - PURPOSE: To evaluate the perioperative safety and mid-term prognosis (<=12 months) of HydroSoft coils in treating ruptured aneurysms at the anterior circulation compared with bare platinum coils. MATERIALS AND METHODS: Patients with aneurysmal subarachnoid hemorrhages admitted to our hospital between January 2009 and March 2012 were retrospectively analyzed. According to strict inclusion and exclusion criteria, cases were selected and classified into two groups: In group A, HydroSoft coils were used as the primary filling coils (>=40 % of total coil length); in group B, only bare platinum coils were used. Cases in both groups were all treated with stent-assistance. A comparison between the two groups was performed for periprocedural complications as well as immediate and mid-term outcomes. The stents used included Enterprise, Neuroform, and Solitaire. RESULTS: Fifty-six aneurysms were in group A patients, and 68 aneurysms were in group B patients. Compared with group B, group A did not have increased incidence of complications but had greater packing attenuation (44.5 +/- 8.8-29.8 +/- 9.1 %, t = 2.577, P = 0.014) and increased initial complete occlusion rates (63-44 %, chi (2) = 4.161, P = 0.041). Radiologic follow-up were performed in 46 patients from group A and 51 patients from group B. Complete occlusion rates at follow-up were significantly greater in group A than in group B (89.1-70.6 %, chi (2) = 5.08, P = 0.043); the difference in recanalization rates were statistically insignificant between the groups (6.5-5.9 %, P = 1.000). CONCLUSION: HydroSoft coils proved safe during the periprocedural period and provided greater initial complete occlusion rates, greater packing density, and better follow-up results compared with bare platinum coils. PMID- 24218174 TI - Centrally inserted external catheters and totally implantable ports for the delivery of chemotherapy: a systematic review and meta-analysis of device-related complications. AB - PURPOSE: This systematic review and meta-analysis aimed to evaluate the risks of complications (infectious and non-infectious) including the need for device removal associated with centrally inserted external catheters compared with totally implantable ports in patients undergoing chemotherapy. METHODS: Relevant major electronic databases were searched from inception to December 2012. All randomized controlled trials (RCT) and observational studies that compared centrally inserted external catheters with totally implantable ports in patients undergoing chemotherapy were included in the systematic review. Meta-analysis was carried out to estimate the odds ratios of device-associated complications, including infection, non-infectious complications and device removal associated with external catheters relative to implantable ports. RESULTS: Overall, five RCTs and 25 observational studies were included in the study. The studies were heterogeneous, and included adults and children, with different types of cancer, undergoing chemotherapy. Based on the pooled estimates from included studies, external catheters were associated with approximately a three to four-fold increase in the risks of infections, non-infectious complications and device removal compared implantable ports. CONCLUSION: The findings of this study showed that totally implantable ports are superior to external catheters in terms of catheter-associated complications. However, a formal health technology assessment on the clinical and cost-effectiveness of the use of implantable ports compared with external catheters is needed to inform policy makers of the relative value of investing in totally implantable devices compared with external catheters. PMID- 24218175 TI - Reply to letter re: general theory of predictive dosimetry for yttrium-90 radioembolization to sites other than the liver. PMID- 24218176 TI - Development of new shaped punch to predict scale-up issue in tableting process. AB - Scale-up issues in the tableting process, such as capping, sticking, or differences in tablet thickness, are often observed at the commercial production scale. A new shaped punch, named the size adjusted for scale-up (SAS) punch, was created to estimate scale-up issues seen between laboratory scale and commercial scale tableting processes. The SAS punch's head shape was designed to replicate the total compression time of a laboratory tableting machine to that of a commercial tableting machine. Three different lubricated blends were compressed into tablets using a laboratory tableting machine equipped with SAS punches, and any differences in tablet thickness or capping phenomenon were observed. It was found that the new shaped punch could be used to replicate scale-up issues observed in the commercial tableting machine. The SAS punch was shown to be a useful tool to estimate scale-up issues in the tableting process. PMID- 24218177 TI - Cathepsin L1 mimotopes with adjuvant Quil A induces a Th1/Th2 immune response and confers significant protection against Fasciola hepatica infection in goats. AB - Thirty goats were randomly allocated in five groups of six animals each, for immunization with 1 * 10(14) phage particles of clones 11, 13, and 13 with Quil A adjuvant and wild-type M13KE phage at the beginning and 4 weeks later. The control group received phosphate-buffered saline. All groups were challenged with 200 metacercariae at week 6 and slaughtered 14 weeks later. The mean worm burdens after challenge were reduced by 46.91% and 79.53% in goats vaccinated with clones 13 and 13 with Quil A (P < 0.05), respectively; no effect was observed in animals immunized with clone 11 and M13KE phage. Animals receiving clones 11, 13, and 13 with Quil A showed a significant reduction in eggs output. Vaccinated animals produced parasite-specific total IgG antibody which were boosted after challenge with metacercariae of F. hepatica. Furthermore, levels of anti-phage total IgG increased rapidly within 2 weeks of the first vaccination and were always significantly higher in all vaccinated goats than in the infected control group. The fluke burden of goats immunized with clones 13 and 13 with Quil A was significantly correlated with IgG2 and total IgG. Goats vaccinated with phage clones produced significantly high titres of IgG1 and IgG2 antibodies indicating a mixed Th1/Th2 response. These data indicate that cathepsin L1 mimotopes has a potential as a vaccine candidate against Fasciola hepatica, whose efficacy will be evaluated in other host species, including those of veterinary importance. PMID- 24218178 TI - Inhibiting and reversing amyloid-beta peptide (1-40) fibril formation with gramicidin S and engineered analogues. AB - In Alzheimer's disease, amyloid-beta (Abeta) peptides aggregate into extracellular fibrillar deposits. Although these deposits may not be the prime cause of the neurodegeneration that characterizes this disease, inhibition or dissolution of amyloid fibril formation by Abeta peptides is likely to affect its development. ThT fluorescence measurements and AFM images showed that the natural antibiotic gramicidin S significantly inhibited Abeta amyloid formation in vitro and could dissolve amyloids that had formed in the absence of the antibiotic. In silico docking suggested that gramicidin S, a cyclic decapeptide that adopts a beta-sheet conformation, binds to the Abeta peptide hairpin-stacked fibril through beta-sheet interactions. This may explain why gramicidin S reduces fibril formation. Analogues of gramicidin S were also tested. An analogue with a potency that was four-times higher than that of the natural product was identified. PMID- 24218179 TI - Pulsed dye laser versus Nd:YAG laser in the treatment of plantar warts: a comparative study. AB - Plantar warts are common viral infection that are usually challenging in treatment. Conventional treatment methods are usually invasive, have low efficacy, and need long recovery periods. In this study, we compared pulsed dye laser (PDL) and neodymium yttrium aluminum garnet (Nd:YAG) lasers in the treatment of recalcitrant plantar warts. The study included 46 patients with multiple plantar warts. In each patient, lesions were divided into two groups: one treated with Nd:YAG (spot size, 7 mm; energy, 100 J/cm(2); and pulse duration, 20 ms) and the other with PDL (spot size, 7 mm; energy, 8 J/cm(2); and pulse duration, 0.5 ms). Laser sessions were applied every 2 weeks with maximum of six sessions. The study included 63% males and 37% females with a mean age of 29.6 +/- 7.34 years. The cure rate was 73.9% with PDL with no significant difference (p = 0.87) from Nd:YAG (78.3%). The number of sessions required was more in PDL (mean, 5.05 +/- 0.2) compared with Nd:YAG (mean, 4.65 +/- 0.5) but without significant difference. Complications were significantly higher with Nd:YAG (43.5%) compared with PDL (8.7%). Hematoma was the most common complication recorded by Nd:YAG (28.3 %), and it was significantly higher (p = 0.002) than PDL (2.2%). Relapse was recorded in 8.7% with Nd:YAG compared with 13% in PDL with no significant difference (p = 0.74). Our results suggested that PDL and Nd:YAG lasers are effective in the treatment of resistant plantar warts. PDL is safer and less painful but needs more sessions, while Nd:YAG is more painful and shows more complications. PMID- 24218180 TI - RAFT-based tri-component fluorescent glycopolymers: synthesis, characterization and application in lectin-mediated bacterial binding study. AB - A group of fluorescent statistical glycopolymers, prepared via reversible addition-fragmentation chain-transfer (RAFT)-based polymerizations, were successfully employed in lectin-mediated bacterial binding studies. The resultant glycopolymers contained three different monomers: N-(2-hydroxyethyl) acrylamide (HEAA), N-(2-aminoethyl) methacrylamide (AEMA) and N-(2-glyconamidoethyl) methacrylamides possessing different pendant sugars. Low dispersities (<=1.32) and predictable degrees of polymerization were observed among the products. After the polymerization, the glycopolymers were further modified by different succinimidyl ester fluorophores targeting the primary amine groups on AEMA. With their binding specificities being confirmed by testing with lectin coated agarose beads, the glycopolymers were employed in bacterial binding studies, where polymers containing alpha-galactose or beta-galactose as the pendant sugar were specifically bound by two clinically important pathogens Pseudomonas aeruginosa and Staphylococcus aureus, respectively. This is the first report of using RAFT based glycopolymers in bacterial binding studies, and the ready access to tri component statistical glycopolymers also warrants further exploration of their utility in other glycobiological applications. PMID- 24218182 TI - Molecular and computational approaches to characterize thermostable laccase gene from two xerophytic plant species. AB - Laccases are blue multicopper oxidases that carry out single electron transfers in the oxidation of phenols to quinones. In plants, they confer structural stability to the cell wall. Thermostable laccases were identified in xerophytes Cereus pterogonus and Opuntia vulgaris that could be used in biotechnology and industrial processes. Polyclonal anti-laccase antibodies were generated against purified laccase enzyme isoforms capable of 98-99% inhibition of the catalytic activity. Antibodies raised against lower molecular weight isoforms inhibited 70% of the catalytic activity of higher molecular forms. Only 20% inhibition was noted when assayed in reverse. A partial gene sequence of thermostable xerophytic laccase comprising 712 and 880 bp was identified employing cDNA as template. The nucleotide sequence was submitted to GenBank. The gene sequence was in silico translated into protein sequence and a 3-D structure was predicted using I-Tasser and Genesilico online servers that justified the experimental observations. Anti laccase antibodies and nucleotide gene sequence of this thermostable plant laccase can be utilized for predicting laccase antigenic sequences and for cloning and expression of the thermostable eukaryotic laccase. PMID- 24218181 TI - Favorable survival and metabolic outcome for children with diencephalic syndrome using a radiation-sparing approach. AB - Diencephalic syndrome (DS) is a clinical disorder of metabolism associated with poor outcome in children with low-grade gliomas (LGGs). Since survival has been primarily reported with aggressive therapy, we report outcome data for these patients using a current, contrasting chemotherapy-driven approach. We performed a population-based review of DS patients treated with chemotherapy from 1997 2012. Metabolic rate was assessed in selected cases using open-circuit calorimetry to generate resting energy expenditure (REE) data. Tumor tissue was analyzed for BRAF alterations. Survival was compared with an age-related, radiotherapy naive cohort of non-DS children with location-matched LGGs. Nine children (1.7% of 520 LGG diagnoses) fulfilled DS criteria. The median diagnostic age was 1.49 years (0.55-2.69 years), although neurofibromatosis Type-I patients were older (p = 0.005). All tumors analyzed exhibited either NF1 mutation or BRAF fusion. Seven tumors were histologically confirmed as low grade astrocytomas, one demonstrated neurocytic features, and one NF1 case was diagnosed using imaging and clinical criteria. All patients received chemotherapy, with seven cases also receiving initial nutritional supplementation. All nine gained weight after only 6 months of treatment. Two DS patients had serial REE measurements, revealing a hypermetabolic state (over 200% of predicted REE) at diagnosis which reduced to normal range with therapy. First-line chemotherapy treatment resulted in one minor response, stable disease in four cases, with progression in the remaining four patients. Although DS patients demonstrated inferior initial progression free survival when compared to non-DS counterparts (5 years: 22 versus 60%, p = 0.015), all DS children remain alive at a median follow up of 5.3 years (1.2-14.9 years) with none requiring radiotherapy. Long-term sequelae included pituitary and visual dysfunction, learning difficulties and paradoxical, inappropriate weight gain. DS can be managed with non-aggressive chemotherapeutic, radiation sparing strategies supplemented by temporary nutritional support. Multiple lines of therapy may be required to overcome disease progression but excellent survival and metabolic outcomes can be achieved. Continued surveillance is mandatory to prevent significant weight gain and support affected children with clinical sequelae. PMID- 24218183 TI - Molecular cloning, characterization, and dye-decolorizing ability of a temperature- and pH-stable laccase from Bacillus subtilis X1. AB - Laccases from fungal origin are typically unstable at high temperatures and alkaline conditions. This characteristic limits their practical applications. In this study, a new bacterial strain exhibiting laccase activity was isolated from raw fennel honey samples and identified as Bacillus subtilis X1. The CotA-laccase gene was cloned from strain X1 and efficiently expressed in Escherichia coli in a biologically active form. The purified recombinant laccase demonstrated an extensive pH range for catalyzing substrates and high stability toward alkaline pH and high temperatures. No loss of laccase activity was observed at pH 9.0 after 10 days of incubation, and approximately 21 % of the initial activity was detected after 10 h at 80 degrees C. Two anthraquinonic dyes (reactive blue 4 and reactive yellow brown) and two azo dyes (reactive red 11 and reactive brilliant orange) could be partially decolorized by purified laccase in the absence of a mediator. The decolorization process was efficiently promoted when methylsyringate was present, with more than 90 % of color removal occurring in 3 h at pH 7.0 or 9.0. These unusual properties indicated a high potential of the novel CotA-laccase for industrial applications. PMID- 24218184 TI - Effect of plasmolysis on protocorm-like bodies of Dendrobium Bobby Messina orchid following cryopreservation with encapsulation-dehydration method. AB - Histological observation and scanning electron microscopy analyses in Dendrobium Bobby Messina indicates the cellular process of cryopreserved protocorm-like bodies (PLBs) was different comparative to non-cryopreserved PLBs. The cellular process was not only modified by the freezing and thawing effect but also due to the dehydration process itself during the cryopreservation procedure. Histological observation in Dendrobium Bobby Messina in encapsulation-dehydration method indicated that the degree of plasmolysis causes more cellular changes to the cryopreserved PLBs comparative to non-cryopreserved and stock culture PLBs. These results revealed higher amount of homogenous cell population and denser cytoplasm in cryopreserved PLBs. Histological analysis also revealed more voluminous nucleus in cryopreserved PLBs comparative to non-cryopreserved PLBs and PLBs stock culture. In contrast, scanning electron microscope analysis showed severe damages in cryopreserved PLBs and non-cryopreserved PLBs comparative to the PLBs stock culture which in return could be the possible reason of no regrowth in encapsulation-dehydration method. Damages incurred were on top part, side part, and at the stomata of the PLBs. Histological observation and scanning electron microscopy analyses in Dendrobium Bobby Messina indicates that the degree of plasmolysis causes changes in the cellular process of PLBs from cryopreserved PLBs was different comparative to non-cryopreserved PLBs. PMID- 24218185 TI - Partial purification and characterization of a novel extracellular tyrosinase from Auricularia auricula. AB - Extracellular tyrosinase from Auricularia auricula RF201 was purified in a three step procedure involving ammonium sulfate precipitation, Sephadex G-100, and DEAE Sepharose column chromatography. The partially purified enzyme showed a single protein band of 12.6 kDa on SDS-PAGE. The optimum pH for tyrosinase activity was 7, and the enzyme was stable between pH 6 and 9. Tyrosinase has optimal activity at 40 degrees C and retained most of its activity between 4 and 50 degrees C. A. auricula tyrosinase could oxidize L-tyrosine, L-DOPA, catechol, and caffeic acid and displayed dark brown or peach color. However, the enzyme was unable to catalyze L-phenylalanine and ferulic acid. In comparison with other substrates, L tyrosine displayed the highest affinity (K m of 0.11 mM) and the maximal reaction velocity (V max of 102.58 MUmol/min). Tyrosinase activity was reduced in the presence of numerous tested compounds. Particularly SDS, it significantly inhibited enzyme activity. CuSO4 and NaCl showed an activation effect on enzyme activity, with the maximum activation found in the presence of CuSO4. PMID- 24218187 TI - Highly effective visible-light-induced H(2) generation by single-layer 1T-MoS(2) and a nanocomposite of few-layer 2H-MoS(2) with heavily nitrogenated graphene. AB - Two sorts of MoS2 : A single-layer, metallic form of MoS2 (1T-MoS2 ) and a nanocomposite of a second form of MoS2 (few-layer 2H-MoS2 ) with heavily nitrogenated reduced graphene oxide (NRGO; N content ca. 15 %) show outstanding performance in the production of H2 under visible-light illumination. PMID- 24218186 TI - Analytical approaches for the determination of phytocannabinoids and endocannabinoids in human matrices. AB - Over the last two decades, the role played by phytocannabinoids and endocannabinoids in medicine has gained increasing interest in the scientific community. Upon identification of the plant compound Delta(9) tetrahydrocannabinol (THC) and of the endogenous substance anandamide (AEA), different methodological approaches and innovative techniques have been developed, in order to evaluate the content of these molecules in various human matrices. In this review, we discuss the analytical methods that are currently used for the identification of phytocannabinoids and endocannabinoids, and we summarize the benefits and limitations of these procedures. Moreover, we provide an overview of the main biological matrices that have been analyzed to date for qualitative detection and quantitative determination of these compounds. PMID- 24218189 TI - Differential humoral responses against heat-shock proteins after autologous stem cell transplantation in multiple myeloma. AB - Heat-shock proteins (HSP) are important molecules in the pathogenesis of multiple myeloma (MM). Their blockages by drugs or cellular immune response have been investigated, and a possible association with the presence of oligoclonal bands (OB) has been postulated in patients with MM after allogenic stem cell transplantation. The aim of the present study was to ascertain the serum antibody levels against three HSP (60, 70 and 90) by ELISA in patients with MM in complete remission after autologous stem cell transplantation (ASCT), with or without OB, and compare them with those patients with stable gammopathy of undetermined significance (MGUS) and healthy controls. Our results in samples after ASCT showed no differential levels of anti-HSP according to the presence or absence of the oligoclonal response. However, higher levels of anti-HSP90 were found in patients with stable MGUS in comparison with MM patients (p = 0.004). In the same line, a longer progression-free survival was observed in those patients who presented higher anti-HSP90 levels after ASCT (p = 0.042). These results suggest, for first time, the potential of anti-HSP90 humoral immune response for long-term control of malignant plasma cell disorders. PMID- 24218190 TI - The effect of gamma radiation on the lipid profile of irradiated red blood cells. AB - An investigation into the effects of irradiation and of the storage time on aging and quality are a relevant issue to ensure the safety and the efficiency of irradiation in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). In this work, the biochemical properties and alterations presented by erythrocyte membranes, up to 28-days post-irradiation, with a dose of 25 Gy, were studied as a function of storage and post-irradiation time. There was a considerable variation in the total of phospholipid content, when comparing the control and irradiated samples, mostly from the third day onwards; and at the same time, the effect occurred as a function on the storage time of blood bags. The levels of total cholesterol decreased 3-9 days after irradiation. TBARS levels were increased after irradiation and 7 days of storage, but no increment of catalase activity was observed after the irradiation. Furthermore, the protein profile was maintained throughout the irradiation and storage time, until the 21st day, with the presence of a protein fragmentation band of around 28 kDa on the 28th day. In conclusion, although gamma irradiation is the main agent for the prevention of TA-GVHD, a better understanding of the physical and biochemical properties of erythrocytes are necessary to better assess their viability, and to be able to issue more secure recommendations on the shelf life of blood bags, and the safe use of the irradiated red cells therein. PMID- 24218191 TI - Untreated preoperative depression is not associated with postoperative arrhythmias in CABG patients. AB - PURPOSE: The mechanism by which depression affects postoperative outcome may involve arrhythmias. The purpose of this study was to evaluate whether untreated depression is associated with an increased incidence of postoperative arrhythmias in patients undergoing coronary artery bypass graft surgery (CABG). METHODS: One hundred seven patients were assessed for signs of depression with the Prime-MD Patient Health Questionnaire (brief PHQ) one week before surgery and subsequently underwent Holter monitoring for 48-72 hr postoperatively. The incidences of atrial fibrillation (AF); supraventricular tachycardia (SVT); ventricular tachycardia (VT), defined as three or more consecutive beats at a cycle length less than 600 msec; ventricular fibrillation (VF); and average heart rate (HR) were recorded in patients with and without signs of depression. RESULTS: The incidence of preoperative untreated depression was 27% (29/107). Twenty patients had mild depression (brief PHQ score of 5-9), seven patients had moderate depression (a score of 10-14), and two patients had severe depression (a score of 20). The incidences of postoperative AF, SVT, and non-sustained VT in depressed and non-depressed patients were 37.9% vs 35.9%, respectively (P = 0.50), 34.4% vs 52.5%, respectively (P = 0.07), and 17.2% vs 37.1%, respectively (P = 0.04). The average (SD) postoperative HR was similar in both groups [95 (12) beats.min(-1) in depressed patients and 92 (10) beats.min(-1) in non-depressed patients, (P = 0.25)]. Multivariate regression analysis showed that older age, but not depression, was a risk factor for postoperative arrhythmia. CONCLUSIONS: Preoperative untreated depression is not related to postoperative arrhythmia in the early postoperative period in patients undergoing elective CABG. This trial was registered at clinicaltrials.gov (number: NCT00622024). PMID- 24218192 TI - Prevention of chronic pain after surgery: new insights for future research and patient care. PMID- 24218193 TI - Not small adults: the emerging role of pediatric pain services. AB - PURPOSE: This review article explores the need for specialized pain care for children and adolescents and provides some historical context for our current knowledge base and clinical practice. PRINCIPAL FINDINGS: Pediatric patients have specialized needs with respect to assessment and management of pain. Acute pain care is modified by developmental considerations in both these areas; chronic pain encompasses a wide range of complex developmental, social, and psychological factors requiring the skills of different health disciplines to provide the best care. CONCLUSIONS: Awareness of children's pain has increased dramatically over the past three decades, and Canadians have performed a leadership role in much of the research. Specific multidisciplinary teams are a more recent phenomenon, but they are shown to be more effective and probably more cost effective than traditional treatment models. Important gaps in availability of resources to manage these patients remain. PMID- 24218194 TI - Use of the King VisionTM video laryngoscope to facilitate fibreoptic intubation in critical tracheal stenosis proves superior to the GlideScope(r). PMID- 24218195 TI - Coumarinylmethyl caging groups with redshifted absorption. AB - The small and synthetically easily accessible coumarinylmethyl backbone has been modified to generate a family of photolabile protecting groups with redshifted absorption. We relied on introducing electron-donating groups in the 7 position and electron-withdrawing groups in the 2-, and 2- and 3 positions. In particular, we showed that the diethylamino-thiocoumarylmethyl and the diethylamino coumarylidenemalononitrilemethyl are relevant for uncaging with cyan light. They both exhibit a significant action cross section for uncaging in the 470-500 nm wavelength range and a low light absorption between 350 and 400 nm. These attractive features are favorable to perform chromatic orthogonal photoactivation with UV and blue-cyan light sources, respectively. PMID- 24218196 TI - Role of histamine in altering fluid recycling in normal and post-traumatic rabbit peritoneum. AB - This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation. PMID- 24218197 TI - Practice implications for preventing population vulnerability related to vitamin D status. AB - PURPOSE: To provide primary care clinicians with practice recommendations for the safe, individualized, effective, efficient evaluation, and treatment of vitamin D status for maximum health promotion and disease prevention. DATA SOURCES: A review and synthesis of current scientific literature on vitamin D was conducted related to the physiologic impact of vitamin D, topics of debate, research and recommendations, adequate serum levels, daily supplementation, and deficiency treatment. CONCLUSIONS: Inadequate vitamin D levels are not isolated to any one geographic, ethnic, or socioeconomic population, and exist without regard to gender, age, or health status. Conflicting vitamin D evidence and recommendations may leave patients vulnerable to vitamin D inadequacy, deficiency, or excess, and in turn, avoidable negative outcomes. IMPLICATIONS FOR NPS: Nurse practitioners (NPs) must actively assess patient vitamin D status and educate patients in order to prevent negative health outcomes. Maintaining adequate vitamin D levels is an easy and cost-efficient adjunct to other health promotion and disease prevention measures. NPs who neglect the physiologic roles of vitamin D and potential patient vulnerability miss an opportunity to make an impact in both patient health and the economic healthcare burden related to acute and chronic disease. PMID- 24218198 TI - ACNP intensivist: a new ICU care delivery model and its supporting educational programs. AB - The purposes of this article are to describe a physician (MD)/acute care nurse practitioner (ACNP) intensivist model for delivery of critical care services in a tertiary academic medical center and to describe an innovative nurse practitioner educational program developed to support the model. In an effort to address the current shortage of intensivists, Vanderbilt Medical Center has developed and refined a multidisciplinary intensivist MD/ACNP teams to provide expanded critical care services. The ACNPs, in collaboration with intensivist MDs, function as intensivist teams and are responsible for developing and executing the daily medical plan, bedside procedures, and emergency response. These teams provide 24-h a day coverage of tertiary level ICUs, and provide several unique benefits over traditional resident ICU staffing models. As the concept of the MD/ACNP intensivist team has developed, Vanderbilt University School of Nursing ACNP Program has expanded its curriculum to provide graduates with the knowledge, skills, and experiences to safely manage unstable critically ill patients. Multidisciplinary critical care teams of MD intensivists who work in collaboration with ACNP intensivists address the current shortfall of intensivists and represent a cost-effective means for expanding ICU coverage and increasing ICU bed availability while maintaining Leap Frog ICU staffing compliance. PMID- 24218199 TI - Advances in menopausal therapy: the tissue-selective estrogen complex. AB - PURPOSE: Most menopausal women experience vasomotor symptoms, vulvar-vaginal atrophy, and/or bone loss. Although available estrogen and progestin therapies are effective in treating menopausal symptoms and preventing bone loss, some women may seek a therapy that provides symptom relief and has an improved tolerability profile. One option is a tissue-selective estrogen complex (TSEC), or the pairing of estrogen(s) with a selective estrogen receptor modulator (SERM) to achieve the benefits of each component with fewer side effects. The first TSEC in clinical development combines the SERM bazedoxifene (BZA) with conjugated estrogens (CEs). The purpose of this article is to review published data for BZA/CE. DATA SOURCES: Data were obtained from phase 3 BZA/CE clinical trial study articles. CONCLUSIONS: Daily BZA 20 mg/CE 0.625 mg or 0.45 mg effectively relieved hot flushes, maintained or increased bone mineral density, treated vulvar-vaginal atrophy, and improved quality of life. Further, BZA prevented stimulation of the endometrium by CE, and resulted in rates of amenorrhea and breast pain similar to placebo. IMPLICATIONS FOR PRACTICE: These results support the use of a TSEC consisting of BZA/CE as a promising therapy for managing the signs and symptoms from reduced estrogen levels associated with menopause. PMID- 24218200 TI - Organizational climate in primary care settings: implications for nurse practitioner practice. AB - PURPOSE: The purpose of this review is to investigate literature related to organizational climate, define organizational climate, and identify its domains for nurse practitioner (NP) practice in primary care settings. DATA SOURCES: A search was conducted using MEDLINE, PubMed, HealthSTAR/Ovid, ISI Web of Science, and several other health policy and nursingy databases. CONCLUSIONS: In primary care settings, organizational climate for NPs is a set of organizational attributes, which are perceived by NPs about their practice setting, emerge from the way the organization interacts with NPs, and affect NP behaviors and outcomes. Autonomy, NP-physician relations, and professional visibility were identified as organizational climate domains. IMPLICATIONS FOR PRACTICE: NPs should be encouraged to assess organizational climate in their workplace and choose organizations that promote autonomy, collegiality between NPs and physicians, and encourage professional visibility. Organizational and NP awareness of qualities that foster NP practice will be a first step for developing strategies to creating an optimal organizational climate for NPs to deliver high-quality care. More research is needed to develop a comprehensive conceptual framework for organizational climate and develop new instruments to accurately measure organizational climate and link it to NP and patient outcomes. PMID- 24218201 TI - Caring for military spouses in primary care. AB - PURPOSE: To provide primary care providers with knowledge of unique challenges faced by military families. By understanding how military families cope with military lifestyle and deployment, providers can be more effective in their care of these patients and offer assistance in optimizing their health. DATA SOURCES: Research articles, World Wide Web search of resources for military families and Department of Defense documents. CONCLUSIONS: Military families are faced with many challenges and hardships such as frequent geographic relocations, social isolation, periodic deployments and separations, and risk of injury and death. Unique stressors associated with deployment include assumption of single parent role, altered finances, change in social support from family and friends, and concerns for the safety of the service member. Ineffective coping with stressors can manifest both physically and/or psychologically. IMPLICATIONS FOR PRACTICE: Healthcare providers should routinely inquire about a patient's possible military affiliation. Military spouses need to be assessed for current stress levels and coping behaviors used in order to provide the most appropriate recommendations and referrals. As healthcare providers, understanding the unique demands of the military lifestyle is necessary to provide effective quality care with optimal health outcomes in this population. PMID- 24218202 TI - Assessment of provider adherence to obesity treatment guidelines. AB - PURPOSE: Despite the presence of obesity treatment guidelines, healthcare providers often provide suboptimal weight management. The purpose of the quality improvement project was to systematically assess adherence with adult overweight/obesity guidelines in primary care to reduce patient risk. DATA SOURCES: Retrospective analysis of 420 encounter notes from overweight and obese adult patients in three primary care clinics. Data were collected before and after a continuing education session for providers on guidelines for optimal management of obesity. Measures of completeness of quality indicators were abstracted from records. CONCLUSIONS: Significant improvement in the completeness score and documentation of body mass index, height, diagnosis of overweight/obesity, and counseling for diet and physical activity were achieved. IMPLICATIONS FOR PRACTICE: The proposed measures for systematically assessing the integration of obesity guidelines in primary care are feasible quality indicators and useful for evidence-based decision making. PMID- 24218203 TI - "I got caught up in the game": generational influences on contraceptive decision making in African-American women. AB - PURPOSE: Reproductive health disparities are a significant issue for African American adolescents. This study was designed to explore the cross-generational influences on adolescent sexuality in a cohort of daughters/granddaughters of U.S. born African-American women. DATA SOURCES: Data were generated through interviews with triads of African-American women: grandmothers, and their daughters and granddaughters, to gain insight into the phenomena of early sexual debut, high rates of unintended pregnancies, HIV/AIDS, and other sexually transmitted infections from a cross-generational perspective. CONCLUSIONS: Six themes emerged from the data: southern influences; a worldview of relationships; communication-key to preparedness; seeking information from mom; "I got caught up in the game"; and contraceptive use and beliefs. In this sample, mothers' and grandmothers' culture, values, and beliefs significantly influenced the adolescents' sexual and reproductive decision making. IMPLICATIONS FOR PRACTICE: Clinicians' knowledge of African-American culture, beliefs, and family values is key when providing guidance about contraception to these young women. PMID- 24218205 TI - Label-free flow cytometry analysis of subvisible aggregates in liquid IgG1 antibody formulations. AB - The objective of this study was to characterize and quantify label-free subvisible antibody particles in different formulations based on their size and physical properties by flow cytometry. Protein subvisible particles were prepared under various stress conditions and analyzed by applying different analytical techniques [light obscuration (LO), microflow imaging (MFI), and flow cytometry (FACS)] for the detection of aggregates. The capability of the FACS method to detect and count subvisible particles was evaluated and benchmarked against conventional techniques. FACS can analyze particles down to 500 nm reducing the gap between size-exclusion chromatography and LO. The applied methods of FACS, LO, and MFI displayed a proportional correlation between the total particle counts, however, FACS can provide additional information on the structural characteristics of such aggregated particles. PMID- 24218206 TI - MeRy-B, a metabolomic database and knowledge base for exploring plant primary metabolism. AB - Plant primary metabolites are organic compounds that are common to all or most plant species and are essential for plant growth, development, and reproduction. They are intermediates and products of metabolism involved in photosynthesis and other biosynthetic processes. Primary metabolites belong to different compound families, mainly carbohydrates, organic acids, amino acids, nucleotides, fatty acids, steroids, or lipids. Until recently, unlike the Human Metabolome Database ( http://www.hmdb.ca ) dedicated to human metabolism, there was no centralized database or repository dedicated exclusively to the plant kingdom that contained information on metabolites and their concentrations in a detailed experimental context. MeRy-B is the first platform for plant (1)H-NMR metabolomic profiles (MeRy-B, http://bit.ly/meryb ), designed to provide a knowledge base of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata. MeRy-B contains lists of plant metabolites, mostly primary metabolites and unknown compounds, with information about experimental conditions, the factors studied, and metabolite concentrations for 19 different plant species (Arabidopsis, broccoli, daphne, grape, maize, barrel clover, melon, Ostreococcus tauri, palm date, palm tree, peach, pine tree, eucalyptus, plantain rice, strawberry, sugar beet, tomato, vanilla), compiled from more than 2,300 annotated NMR profiles for various organs or tissues deposited by 30 different private or public contributors in September 2013. Currently, about half of the data deposited in MeRy-B is publicly available. In this chapter, readers will be shown how to (1) navigate through and retrieve data of publicly available projects on MeRy-B website; (2) visualize lists of experimentally identified metabolites and their concentrations in all plant species present in MeRy-B; (3) get primary metabolite list for a particular plant species in MeRy-B; and for a particular tissue (4) find information on a primary metabolite regardless of the species. PMID- 24218204 TI - Co-regulation of polysaccharide production, motility, and expression of type III secretion genes by EnvZ/OmpR and GrrS/GrrA systems in Erwinia amylovora. AB - The EnvZ/OmpR and GrrS/GrrA systems, two widely distributed two-component systems in gamma-Proteobacteria, negatively control amylovoran biosynthesis in Erwinia amylovora, and the two systems regulate motility in an opposing manner. In this study, we examined the interplay of EnvZ/OmpR and GrrS/GrrA systems in controlling various virulence traits in E. amylovora. Results showed that amylovoran production was significantly higher when both systems were inactivated, indicating that the two systems act as negative regulators and their combined effect on amylovoran production appears to be enhanced. In contrast, reduced motility was observed when both systems were deleted as compared to that of grrA/grrS mutants and WT strain, indicating that the two systems antagonistically regulate motility in E. amylovora. In addition, glycogen accumulation was much higher in envZ/ompR and two triple mutants than that of grrS/grrA mutants and WT strain, suggesting that EnvZ/OmpR plays a dominant role in regulating glycogen accumulation, whereas levan production was significantly lower in the grrS/grrA and two triple mutants as compared with that of WT and envZ/ompR mutants, indicating that GrrS/GrrA system dominantly controls levan production. Furthermore, both systems negatively regulated expression of three type III secretion (T3SS) genes and their combined negative effect on hrp-T3SS gene expression increased when both systems were deleted. These results demonstrated that EnvZ/OmpR and GrrS/GrrA systems co-regulate various virulence factors in E. amylovora by still unknown mechanisms or through different target genes, sRNAs, or proteins, indicating that a complex regulatory network may be involved, which needs to be further explored. PMID- 24218207 TI - Targeted deuteration of polyphenolics for their qualitative and quantitative metabolomic analysis in plant-derived extracts. AB - Polyphenolics are a chemically diverse class of plant specialized metabolites with strong antioxidant properties, and their consumption has been associated with improved human health. Metabolomic analysis of these compounds in both plant and mammalian samples has relied predominantly on liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS). Due to variable matrix effects across samples during ionization, the accuracy of this approach for quantifying compounds is greatly improved by incorporating stable isotope-labeled standards into the sample prior to analysis. However, commercially available, stable isotope-labeled, polyphenolic standards are both limited and costly. Here we present a protocol for generating stable isotope-labeled polyphenolics based on their deuteration by mild acid-catalyzed, electrophilic aromatic substitution. Importantly, this protocol is effective for generating stable isotope-labeled standards of many biologically relevant polyphenolics, both aglycones and the various conjugated forms alike. PMID- 24218208 TI - Relative quantitation in single-cell metabolomics by laser ablation electrospray mass spectrometry. AB - Single-cell analysis of metabolites by mass spectrometry (MS) is challenging due to the very limited volume and inherent molecular complexity of the sample. Quantitative metabolomic analysis of individual cells provides information on the metabolic heterogeneity of cells unattainable by aggregate analysis of multiple cells. Depending on the ionization method, MS can offer quantitative analysis for a broad class of metabolites exhibiting both high sensitivity and selectivity. Laser ablation electrospray ionization (LAESI) has been successfully exploited to analyze metabolites from broad range of biological samples, including single cells and small cell populations. In this work, we describe a protocol for the relative quantitation of metabolites in single cells by LAESI-mass spectrometry. PMID- 24218209 TI - Quantification of plant volatiles. AB - Plant volatiles occupy diverse roles as signaling molecules, defensive compounds, hormones, and even waste products. Exponential growth in the related literature coupled with the availability of new analytical and computational technologies has inspired novel avenues of inquiry while giving researchers the tools to analyze the plant metabolome to an unprecedented level of detail. As availability of instrumentation and the need for qualitative and especially quantitative metabolic analysis grow within the scientific community so does the need for robust, adaptable, and widely disseminated protocols to enable rapid progression from experimental design to data analysis with minimal input toward method development. This protocol describes the collection and quantitative analysis of plant volatile headspace compounds. It is intended to guide those with little to no experience in analytical chemistry in the quantification of plant volatiles using gas chromatography coupled to mass spectrometry by describing procedures for calibrating and optimizing collection and analysis of these diverse compounds. PMID- 24218210 TI - Quantitative imaging approaches for small-molecule measurements using FRET sensors in plants. AB - Cellular metabolites and ions can exhibit very specific spatiotemporal dynamics that are very challenging to monitor using extraction-based methods. Genetically encoded Foster resonance energy transfer sensors afford a powerful method of measuring these dynamics in situ and hence are now widely used in order to decode information communicated through the dynamics of cellular metabolites and ions. This methodology involves (1) the development of a suitable sensor, (2) genetic engineering of the sensor for its expression in the tissue of interest, and (3) measurement and characterization of the cellular metabolites and ions using optical imaging. This chapter describes the measurement aspects. We describe the imaging setup, sample preparation from leaf discs and root cells, performance of a perfusion experiment, and quantification of metabolite and ion concentrations from the imaging data. We also describe post-experiment analysis including estimation of sensor efficiency and spectral bleedthrough. PMID- 24218211 TI - Isotopomer measurement techniques in metabolic flux analysis I: nuclear magnetic resonance. AB - Two-dimensional [(1)H, (13)C] heteronuclear single quantum correlation (HSQC) spectroscopy nuclear magnetic resonance (NMR) is a comprehensive tool in metabolic flux analysis using (13)C-labeling experiments. NMR is particularly relevant when extensive isotopomer measurements are required, such as for plant cells and tissues, which contain multiple cellular compartments. Several isotope isomers (isotopomers) can be detected and their distribution extracted quantitatively from a single 2-D HSQC NMR spectrum. For example, 2-D HSQC detects the labeling patterns of adjacent carbon atoms and provides the enrichment of individual carbon atoms of the amino acids and glucosyl and mannosyl units present in hydrolysates of glycosylated protein. The HSQC analysis can quantitatively distinguish differences between the glucosyl units in the starch hydrolysate and a protein hydrolysate of plant biomass: this specifies crucial information about compartmentalization in the plant system. The peak structures obtained from the HSQC experiment show multiplet patterns that are directly related to the isotopomer abundances. These abundances have a nonlinear relationship to the fluxes via isotopomer balancing. Fluxes are obtained from the numerical solution of these balances and a stoichiometric model that includes biomass composition data as well as consumption rates of carbohydrate and nitrogen sources. Herein, we describe the methods for the experimental measurements for flux analysis, i.e., determination of the biomass composition (lipid, protein, soluble sugar, and starch) as well as detailed procedures of acid hydrolysis of protein and starch samples and NMR sample preparation, using soybean embryo culture as the model plant system. Techniques to obtain the relative intensity of 16 amino acids and glucosyl units for protein hydrolysate and the glucosyl units of starch hydrolysate of soybean embryos in 2-D HSQC NMR spectra also are provided. PMID- 24218212 TI - Isotopomer measurement techniques in metabolic flux analysis II: mass spectrometry. AB - Mass spectrometry (MS) offers a sensitive, reliable, and highly accurate method for measurement of isotopic labeling, which is required for generating comprehensive flux maps using metabolic flux analysis (MFA). We present protocols for assessing isotope labeling in a wide range of biochemical species, including proteinogenic amino acids, free organic and amino acids, sugar phosphates, lipids, starch-glucose, and RNA-ribose. We describe the steps of sample preparation, MS analysis, and data handling required to obtain high-quality isotope labeling measurements that are applicable to MFA. By selecting target analytes that maximize identifiability of the key fluxes of interest, MS measurements of isotope labeling can provide a powerful platform for assessing metabolic fluxes in complex biochemical networks. PMID- 24218213 TI - Mathematical modeling of isotope labeling experiments for metabolic flux analysis. AB - Isotope labeling experiments (ILEs) offer a powerful methodology to perform metabolic flux analysis. However, the task of interpreting data from these experiments to evaluate flux values requires significant mathematical modeling skills. Toward this, this chapter provides background information and examples to enable the reader to (1) model metabolic networks, (2) simulate ILEs, and (3) understand the optimization and statistical methods commonly used for flux evaluation. A compartmentalized model of plant glycolysis and pentose phosphate pathway illustrates the reconstruction of a typical metabolic network, whereas a simpler example network illustrates the underlying metabolite and isotopomer balancing techniques. We also discuss the salient features of commonly used flux estimation software 13CFLUX2, Metran, NMR2Flux+, FiatFlux, and OpenFLUX. Furthermore, we briefly discuss methods to improve flux estimates. A graphical checklist at the end of the chapter provides a reader a quick reference to the mathematical modeling concepts and resources. PMID- 24218214 TI - Optimal design of isotope labeling experiments. AB - Stable isotope labeling experiments (ILE) constitute a powerful methodology for estimating metabolic fluxes. An optimal label design for such an experiment is necessary to maximize the precision with which fluxes can be determined. But often, precision gained in the determination of one flux comes at the expense of the precision of other fluxes, and an appropriate label design therefore foremost depends on the question the investigator wants to address. One could liken ILE to shadows that metabolism casts on products. Optimal label design is the placement of the lamp; creating clear shadows for some parts of metabolism and obscuring others.An optimal isotope label design is influenced by: (1) the network structure; (2) the true flux values; (3) the available label measurements; and, (4) commercially available substrates. The first two aspects are dictated by nature and constrain any optimal design. The second two aspects are suitable design parameters. To create an optimal label design, an explicit optimization criterion needs to be formulated. This usually is a property of the flux covariance matrix, which can be augmented by weighting label substrate cost. An optimal design is found by using such a criterion as an objective function for an optimizer. This chapter uses a simple elementary metabolite units (EMU) representation of the TCA cycle to illustrate the process of experimental design of isotope labeled substrates. PMID- 24218215 TI - Putting The Plant Metabolic Network pathway databases to work: going offline to gain new capabilities. AB - Metabolic databases such as The Plant Metabolic Network/MetaCyc and KEGG PATHWAY are publicly accessible resources providing organism-specific information on reactions and metabolites. KEGG PATHWAY depicts metabolic networks as wired, electronic circuit-like maps, whereas the MetaCyc family of databases uses a canonical textbook-like representation. The first MetaCyc-based database for a plant species was AraCyc, which describes metabolism in the model plant Arabidopsis. This database was created over 10 years ago and has since then undergone extensive manual curation to reflect updated information on enzymes and pathways in Arabidopsis. This chapter describes accessing and using AraCyc and its underlying Pathway Tools software. Specifically, methods for (1) navigating Pathway Tools, (2) visualizing omics data and superimposing the data on a metabolic pathway map, and (3) creating pathways and pathway components are discussed. PMID- 24218216 TI - Elucidation of metabolic pathways from enzyme classification data. AB - The IUBMB Enzyme List is widely used by other databases as a source for avoiding ambiguity in the recognition of enzymes as catalytic entities. However, it was not designed for metabolic pathway tracing, which has become increasingly important in systems biology. A Reactions Database has been created from the material in the Enzyme List to allow reactions to be searched by substrate/product, and pathways to be traced from any selected starting/seed substrate. An extensive synonym glossary allows searches by many of the alternative names, including accepted abbreviations, by which a chemical compound may be known. This database was necessary for the development of the application Reaction Explorer ( http://www.reaction-explorer.org ), which was written in Real Studio ( http://www.realsoftware.com/realstudio/ ) to search the Reactions Database and draw metabolic pathways from reactions selected by the user. Having input the name of the starting compound (the "seed"), the user is presented with a list of all reactions containing that compound and then selects the product of interest as the next point on the ensuing graph. The pathway diagram is then generated as the process iterates. A contextual menu is provided, which allows the user: (1) to remove a compound from the graph, along with all associated links; (2) to search the reactions database again for additional reactions involving the compound; (3) to search for the compound within the Enzyme List. PMID- 24218217 TI - Deducing intracellular distributions of metabolic pathways from genomic data. AB - In the recent years, a large number of genomes from a variety of different organisms have been sequenced. Most of the sequence data has been publicly released and can be assessed by interested users. However, this wealth of information is currently underexploited by scientists not directly involved in genome annotation. This is partially because sequencing, assembly, and automated annotation can be done much faster than the identification, classification, and prediction of the intracellular localization of the gene products. This part of the annotation process still largely relies on manual curation and addition of contextual information. Users of genome databases who are unfamiliar with the types of data available from (whole) genomes might therefore find themselves either overwhelmed by the vast amount and multiple layers of data or dissatisfied with less-than-meaningful analyses of the data.In this chapter we present procedures and approaches to identify and characterize gene models of enzymes involved in metabolic pathways based on their similarity to known sequences. Furthermore we describe how to predict the subcellular location of the proteins using publicly available prediction servers and how to interpret the obtained results. The strategies we describe are generally applicable to organisms with primary plastids such as land plants or green algae. Additionally, we describe strategies suitable for those groups of algae with secondary plastids (for instance diatoms), which are characterized by a different cellular topology and a larger number of intracellular compartments compared to plants. PMID- 24218218 TI - Genome-scale models of plant metabolism. AB - A genome-scale model (GSM) is an in silico metabolic model comprising hundreds or thousands of chemical reactions that constitute the metabolic inventory of a cell, tissue, or organism. A complete, accurate GSM, in conjunction with a simulation technique such as flux balance analysis (FBA), can be used to comprehensively predict cellular metabolic flux distributions for a given genotype and given environmental conditions. Apart from enabling a user to quantitatively visualize carbon flow through metabolic pathways, these flux predictions also facilitate the hypothesis of new network properties. By simulating the impacts of environmental stresses or genetic interventions on metabolism, GSMs can aid the formulation of nontrivial metabolic engineering strategies. GSMs for plants and other eukaryotes are significantly more complicated than those for prokaryotes due to their extensive compartmentalization and size. The reconstruction of a GSM involves creating an initial model, curating the model, and then rendering the model ready for FBA. Model reconstruction involves obtaining organism-specific reactions from the annotated genome sequence or organism-specific databases. Model curation involves determining metabolite protonation status or charge, ensuring that reactions are stoichiometrically balanced, assigning reactions to appropriate subcellular compartments, deleting generic reactions or creating specific versions of them, linking dead-end metabolites, and filling of pathway gaps to complete the model. Subsequently, the model requires the addition of transport, exchange, and biomass synthesis reactions to make it FBA-ready. This cycle of editing, refining, and curation has to be performed iteratively to obtain an accurate model. This chapter outlines the reconstruction and curation of GSMs with a focus on models of plant metabolism. PMID- 24218219 TI - Elementary flux modes, flux balance analysis, and their application to plant metabolism. AB - In recent years the number of sequenced and annotated plant genomes has increased significantly, and novel approaches are required to retrieve valuable information from these data sets. The field of systems biology has accelerated the simulation and prediction of phenotypes derived from specific genotypic modifications under defined growth conditions. The biochemical potential of a cell from a specific plant tissue (e.g., seed endosperm) can be derived from its genome in the form of a mathematical model by the method of metabolic network reconstruction. This model can be further analyzed by studying its network properties, analyzing feasible pathway routes through the network, or simulating possible flux distributions of the network . Here, we describe two approaches for identification of all feasible routes through the network (elementary mode analysis) and for simulation of flux distribution in the network based on plant physiological uptake and excretion rates (flux balance analysis). PMID- 24218220 TI - Systems approaches to unraveling plant metabolism: identifying biosynthetic genes of secondary metabolic pathways. AB - The diversity of useful compounds produced by plant secondary metabolism has stimulated broad systems biology approaches to identify the genes involved in their biosynthesis. Systems biology studies in non-model plants pose interesting but addressable challenges, and have been greatly facilitated by the ability to grow and maintain plants, develop laboratory culture systems, and profile key metabolites in order to identify critical genes involved their biosynthesis. In this chapter we describe a suite of approaches that have been useful in Actaea racemosa (L.; syn. Cimicifuga racemosa, Nutt., black coshosh), a non-model medicinal plant with no genome sequence and little horticultural information available, that have led to the development of initial gene-metabolite relationships for the production of several bioactive metabolites in this multicomponent botanical therapeutic, and that can be readily applied to a wide variety of under-characterized medicinal plants. PMID- 24218221 TI - Applications of kinetic modeling to plant metabolism. AB - The importance of kinetic modeling for understanding the control and regulation of complex metabolic networks is increasingly being recognized. Kinetic models encapsulate the available kinetic information of all the enzymes in a pathway, and then calculate the complex behavior that emerges from the interactions between these network components. Kinetic models are particularly useful because they can simulate untested scenarios and thus explore pathway behavior beyond the realm of what is experimentally available or currently feasible. Models can also suggest new experiments in a directed approach.This chapter provides a brief introduction to kinetic modeling and its application to plant metabolic pathways. A two-pronged strategy is followed: first, a method is presented for further analysis of existing published models, with references to the relevant databases housing such models and instructions on how to load the models into simulation software. Next, the requirements for and processes of constructing and validating a kinetic model from scratch are outlined. To conclude, potential applications of models are summarized. PMID- 24218222 TI - Kinetic modeling of plant metabolism and its predictive power: peppermint essential oil biosynthesis as an example. AB - The integration of mathematical modeling with analytical experimentation in an iterative fashion is a powerful approach to advance our understanding of the architecture and regulation of metabolic networks. Ultimately, such knowledge is highly valuable to support efforts aimed at modulating flux through target pathways by molecular breeding and/or metabolic engineering. In this article we describe a kinetic mathematical model of peppermint essential oil biosynthesis, a pathway that has been studied extensively for more than two decades. Modeling assumptions and approximations are described in detail. We provide step-by-step instructions on how to run simulations of dynamic changes in pathway metabolites concentrations. PMID- 24218223 TI - Bicontinuous cubic liquid crystalline nanoparticles for oral delivery of Doxorubicin: implications on bioavailability, therapeutic efficacy, and cardiotoxicity. AB - PURPOSE: The present study explores the potential of bicontinous cubic liquid crystalline nanoparticles (LCNPs) for improving therapeutic potential of doxorubicin. METHODS: Phytantriol based Dox-LCNPs were prepared using hydrotrope method, optimized for various formulation components, process variables and lyophilized. Structural elucidation of the reconstituted formulation was performed using HR-TEM and SAXS analysis. The developed formulation was subjected to exhaustive cell culture experiments for delivery potential (Caco-2 cells) and efficacy (MCF-7 cells). Finally, in vivo pharmacokinetics, pharmacodynamic studies in DMBA induced breast cancer model and cardiotoxicity were also evaluated. RESULTS: The reconstituted formulation exhibited Pn3m type cubic structure, evident by SAXS and posed stability in simulated gastrointestinal fluids and at accelerated stability conditions for 6 months. Dox-LCNPs revealed significantly higher cell cytotoxicity (16.23-fold) against MCF-7 cell lines as compared to free drug owing to its preferential localization in the vicinity of nucleus. Furthermore, Caco-2 cell experiments revealed formation of reversible "virtual pathways" in the cell membrane for Dox-LCNPs and hence posed significantly higher relative oral bioavailability (17.74-fold). Subsequently, Single dose of Dox-LCNPs (per oral) led to significant reduction in % tumor burden (~42%) as compared that of ~31% observed in case of Adriamycin(r) (i.v.) when evaluated in DMBA induced breast cancer model. Moreover, Dox induced cardiotoxicity was also found to be significantly lower in case of Dox-LCNPs as compared to clinical formulations (Adriamycin(r) and Lipodox(r)). CONCLUSION: Incorporation of Dox in the novel LCNPs demonstrated improved antitumor efficacy and safety profile and can be a viable option for oral chemotherapy. PMID- 24218224 TI - Targeting tamoxifen to breast cancer xenograft tumours: preclinical efficacy of folate-attached nanoparticles based on alginate-cysteine/disulphide-bond-reduced albumin. AB - PURPOSE: In vivo evaluation of tamoxifen (TMX)-loaded folate-targeted nanoparticles prepared from a mixture of disulphide bond reduced bovine serum albumin (BSA-SH) and alginate-cysteine (ALG-CYS) as targeted delivery systems of TMX to tumour tissues. METHODS: TMX in solution, TMX included into folate nanoparticles and their non-targeted analogues were intravenously administered to nude mice carrying xenograft MCF-7 tumours. The antitumor activity of these systems was characterized in terms of tumour growth rate, histological and immunohistochemical analysis of tumour tissues and TMX biodistribution. RESULTS: TMX-folate-attached nanoparticles caused tumour remission whereas free TMX or TMX non-targeted nanoparticles could only stop the tumour development. The histological evaluation of tumour tissues showed that those treated with folate conjugated systems presented the most quiescent and disorganized structures. Additionally, the lowest concentrations of TMX accumulated in non-targeted organs were also found after administration of the drug using this formulation. CONCLUSIONS: This study demonstrated that TMX-loaded folate-targeted systems were capable of reaching tumour sites, so enhancing the in vivo anticancer action of TMX, and allowing a new administration route to be applied and some of the current TMX therapy problems to be overcome. PMID- 24218225 TI - Physically and psychologically hazardous jobs and mental health in Thailand. AB - This paper investigates associations between hazardous jobs, mental health and wellbeing among Thai adults. In 2005, 87 134 distance-learning students from Sukhothai Thammathirat Open University completed a self-administered questionnaire; at the 2009 follow-up 60 569 again participated. Job characteristics were reported in 2005, psychological distress and life satisfaction were reported in both 2005 and 2009. We derived two composite variables grading psychologically and physically hazardous jobs and reported adjusted odds ratios (AOR) from multivariate logistic regressions. Analyses focused on cohort members in paid work: the total was 62 332 at 2005 baseline and 41 671 at 2009 follow-up. Cross-sectional AORs linking psychologically hazardous jobs to psychological distress ranged from 1.52 (one hazard) to 4.48 (four hazards) for males and a corresponding 1.34-3.76 for females. Similarly AORs for physically hazardous jobs were 1.75 (one hazard) to 2.76 (four or more hazards) for males and 1.70-3.19 for females. A similar magnitude of associations was found between psychologically adverse jobs and low life satisfaction (AORs of 1.34-4.34 among males and 1.18-3.63 among females). Longitudinal analyses confirm these cross-sectional relationships. Thus, significant dose-response associations were found linking hazardous job exposures in 2005 to mental health and wellbeing in 2009. The health impacts of psychologically and physically hazardous jobs in developed, Western countries are equally evident in transitioning Southeast Asian countries such as Thailand. Regulation and monitoring of work conditions will become increasingly important to the health and wellbeing of the Thai workforce. PMID- 24218226 TI - A guide to imaging in bariatric surgery. AB - There has been an increase in utilization of bariatric surgery and, as with any surgical procedure, the associated risk of complications. Many of the post bariatric surgical complications can be acute, necessitating an emergency room visit and imaging evaluation. Radiologists, especially in the emergency setting, need to be familiar with normal post-operative appearances and potential surgical complications. This review focuses on various bariatric surgical procedures that are performed, and illustrates normal and abnormal radiographic appearances seen on post-operative fluoroscopic upper GI studies and abdominal pelvis CT examinations. PMID- 24218227 TI - Evaluation of calcium and magnesium in scalp hair samples of population consuming different drinking water: risk of kidney stone. AB - The objective of this study was to examine the relationship between calcium (Ca) and magnesium (Mg) in underground water (UGW), bottled mineral water (BMW), and domestic treated water (DTW) with related to risk of kidney stones. The water samples were collected from different areas of Sindh, Pakistan. The scalp hair samples of both genders, age ranged 30-60 years, consuming different types of water, have or have not kidney disorders, were selected. The Ca and Mg concentrations were determined in scalp hair of study subjects and water by flame atomic absorption spectroscopy. The Ca and Mg contents in different types of drinking water, UGW, DTW, and BMW, were found in the range of 79.1-466, 23.7-140, and 45-270 mg/L and 4.43-125, 5.23-39.6, and 7.16-51.3 mg/L, respectively. It was observed that Ca concentration in the scalp hair samples of kidney stone patients consuming different types of drinking water was found to be higher (2,895-4721 MUg/g) while Mg level (84.3-101 MUg/g) was lower as compare to referents subjects (2,490-2,730 MUg/g for Ca, 107-128 MUg/g for Mg) in both genders. The positive correlation was found between Ca and Mg levels in water with related to kidney stone formations in population, especially who consumed underground water. A relative risk and odd ratio were calculated; the relative risk had a strong positive association with incidence of kidney stone which depends on types of drinking water. PMID- 24218228 TI - Relationship between dietary magnesium, manganese, and copper and metabolic syndrome risk in Korean adults: the Korea National Health and Nutrition Examination Survey (2007-2008). AB - Recent studies have reported correlations between mineral intake and metabolic syndrome (MS), but accurate relationships and consistency in the results are difficult to confirm. Accordingly, this study aims to assess the dietary intakes of magnesium (Mg), manganese (Mn), and copper (Cu) to determine their relationship with MS. Data from a total of 5,136 adults (2,084 men, 3,052 women) was collected from the 2007-2008 Korea National Health and Nutrition Examination Survey (KNHANES), and the intakes of Mg, Mn, and Cu of the MS patients were compared with those of healthy adults. The relationship between the intakes of these minerals and the MS risks was analyzed. Diagnosis of MS was evaluated by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) standards. Among all study subjects, 25.9 % (540 subjects) of the men and 24.5 % (748 subjects) of the women met diagnostic criteria for inclusion in the MS group. In the men, daily intakes of Mg and Cu in the MS group were significantly lower than those in control group, and in the women, daily intakes of energy, Mg, Mn, and Cu in the MS group were significantly lower than those of the control group. The women subjects with high blood pressure showed significantly lower intakes of Mg, Mn, and Cu than control subjects. In addition, in the women, the highest quartile of Mg and Cu was inversely associated with MS, but with adjustment were not maintained. However, in the postmenopausal women, MS was significant and inversely associated with the highest quartiles of Cu intake and the association remained significant after adjustments. Considering that MS incidence increases and dietary intake and nutrient density decrease with increasing age, and mineral intake is reduced accordingly, these results suggest that meal management with adequate mineral intake is advisable to control MS. PMID- 24218229 TI - Effect of selenomethionine supplementation in food on the excretion and toxicity of arsenic exposure in female mice. AB - Selenium (Se) is an essential component of several major metabolic pathways and controls immune function. Arsenic (As) is a human carcinogen with immunotoxic and genotoxic activities, functioning mainly by producing oxidative stress. Due to the ability of Se to interact with As and to possibly block its toxic effects, we investigated the impact of dietary Se-methionine (Se-Met) supplementation on the toxicity of As exposure in vivo in a mouse model. Sufficient and excess levels of Se-Met (0.2 and 2 ppm, respectively) were fed to C57BL/6N female mice exposed to sodium arsenite (3, 6 and 10 mg/kg) in tap water for 9 days. We observed that As exposure increased Se-Met excretion in the urine. Se-Met supplementation increased the relative liver weight and decreased the concentration of total liver proteins in animals exposed to 10 mg/kg of As. Se-Met supplementation maintained a normal pool of glutathione in the liver and increased glutathione peroxidase concentration, although the lipoperoxidation level was increased by Se Met even without As exposure. Se-Met supplementation helped to maintain the CD4/CD8 ratio of lymphocytes in the spleen, although it increased the proportion of B cells. Se-Met supplementation prior to As exposure increased the secretion of interleukin-4, IL-12 and interferon-gamma and the stimulation index of the spleen cells in in vitro assays. Se-Met intake improved the basal immunological parameters but did not reduce the damage caused by oxidative stress after low dose As exposure. PMID- 24218230 TI - Symmetry-guided synthesis of highly porous metal-organic frameworks with fluorite topology. AB - Two stable, non-interpenetrated MOFs, PCN-521 and PCN-523, were synthesized by a symmetry-guided strategy. Augmentation of the 4-connected nodes in the fluorite structure with a rigid tetrahedral ligand and substitution of the 8-connected nodes by the Zr/Hf clusters yielded MOFs with large octahedral interstitial cavities. They are the first examples of Zr/Hf MOFs with tetrahedral linkers. PCN 521 has the largest BET surface area (3411 m(2) g(-1)), pore size (20.5*20.5*37.4 A) and void volume (78.5%) of MOFs formed from tetrahedral ligands. This work not only demonstrates a successful implementation of rational design of MOFs with desired topology, but also provides a systematic way of constructing non interpenetrated MOFs with high porosity. PMID- 24218231 TI - A novel method of identifying Mycobacterium tuberculosis Beijing strains by detecting SNPs in Rv0444c and Rv2629. AB - A particular genotype of tuberculosis, named Beijing strain, is strongly associated with drug resistance and high virulence. Therefore, rapid prospective identification of Mycobacterium tuberculosis Beijing strains is very important for identifying and controlling tuberculosis of Beijing genotype. In the present study, we found that the co-mutation, A191C in Rv2629 and G243C in Rv0444c, is closely related to Beijing genotype. Gene Rv2629 and Rv0444c of 139 clinical isolates of M. tuberculosis were analyzed by PCR amplification and sequencing. Among 99 Beijing strains, 86 % (n = 85) isolates had the mutation G243C in Rv0444c and 92.93 % (n = 92) isolates had the mutation A191C in Rv2629. Among 40 non-Beijing isolates, only six isolates carried the mutation G243C in Rv0444c and eight isolates carried the mutation A191C in Rv2629. The co-mutation existed in 84.85 % (n = 84) of 99 clinical genome samples of W-Beijing strains and in only 12.5 % (n = 5) of the 40 non-Beijing strains, and the positive predictive value of 94.38 %, obtained in our experiment with a designed ratio of Beijing isolates, is similar to that in China at present. This result suggested that the detection method of the co-mutation, A191C in Rv2629 and G243C in Rv0444c, proposed in this study was a rapid, reliable, and sensitive one for identifying tuberculosis with Beijing genotype. PMID- 24218233 TI - Identifying and managing nonsuicidal self-injurious behavior in the primary care setting. AB - PURPOSE: To provide an overview of nonsuicidal self-injurious behavior (NSSIB) for nurse practitioners (NPs) who see patients with this complex phenomenon in primary care settings. DATA SOURCES: Selected research and clinical reviews. CONCLUSIONS: NSSIB is characterized as a low-lethality, repetitive act that can alter or cause damage to the body tissue. Among researchers and those who work directly with young people, there is a general consensus that NSSIB is increasing in prevalence. Unfortunately, NPs often view self-injuring patients negatively, likely because of a lack of knowledge as to how to help this special patient population. IMPLICATIONS FOR PRACTICE: Appropriate treatment can be initiated in the primary care setting; however, NPs must be aware of how and when to refer to specialty mental health services. Those with psychiatric comorbidities such as mood lability, anxiety, chronic emptiness or depersonalization, dysphoria, loneliness, anhedonia, or borderline personality disorder require management by mental health specialists. Patients experiencing NSSIB in response to command auditory hallucinations need immediate medical attention. PMID- 24218232 TI - Resveratrol protects DAergic PC12 cells from high glucose-induced oxidative stress and apoptosis: effect on p53 and GRP75 localization. AB - Resveratrol (RESV), a polyphenolic natural compound, has long been acknowledged to have cardioprotective and antiinflammatory actions. Evidence suggests that RESV has antioxidant properties that reduce the formation of reactive oxygen species leading to oxidative stress and apoptotic death of dopaminergic (DAergic) neurons in Parkinson's disease (PD). Recent literature has recognized hyperglycemia as a cause of oxidative stress reported to be harmful for the nervous system. In this context, our study aimed (a) to evaluate the effect of RESV against high glucose (HG)-induced oxidative stress in DAergic neurons, (b) to study the antiapoptotic properties of RESV in HG condition, and c) to analyze RESV's ability to modulate p53 and GRP75, a p53 inactivator found to be under expressed in postmortem PD brains. Our results suggest that RESV protects DAergic neurons against HG-induced oxidative stress by diminishing cellular levels of superoxide anion. Moreover, RESV significantly reduces HG-induced apoptosis in DAergic cells by modulating DNA fragmentation and the expression of several genes implicated in the apoptotic cascade, such as Bax, Bcl-2, cleaved caspase-3, and cleaved PARP-1. RESV also prevents the pro-apoptotic increase of p53 in the nucleus induced by HG. Such data strengthens the correlation between hyperglycemia and neurodegeneration, while providing new insight on the high occurrence of PD in patients with diabetes. This study enlightens potent neuroprotective roles for RESV that should be considered as a nutritional recommendation for preventive and/or complementary therapies in controlling neurodegenerative complications in diabetes. PMID- 24218234 TI - Moyamoya disease: a case of vanishing cerebral vessels. AB - PURPOSE: To provide an overview of moyamoya disease (MMD) including pathophysiology, epidemiology, clinical presentation, diagnosis, treatment, and prognosis. DATA SOURCES: Selected clinical and epidemiological studies, review articles, and diagnostic guidelines for MMD. CONCLUSIONS: MMD is a rare cerebrovascular disease characterized by progressive stenosis of the distal internal carotid arteries and their major branches. The dilated and fragile basal collateral circulations display a "puff of smoke" appearance and thus are called moyamoya vessels. Other unique features of MMD include 2:1 female preponderance and its peak incidence in two age groups: early childhood and adults in their mid 40s. The pathophysiology of MMD is unclear and possible causes include genetic linkage, angiogenesis, autoimmune disease, cranial radiation, and infection of the head and neck. Most patients are symptomatic and may present with ischemic or hemorrhagic strokes, seizure, or headache. The diagnosis depends on clinical presentation and radiographic imaging, and disease progression may be halted with direct or indirect cerebral revascularization. IMPLICATIONS FOR PRACTICE: It is important to make a correct diagnosis and provide appropriate treatment to reduce the morbidity and mortality associated with MMD. A prompt referral for possible surgical revascularization offers the best chance to reduce additional cerebral injuries and improve clinical outcomes. PMID- 24218235 TI - The consensus model for regulation of APRNs: implications for nurse practitioners. AB - PURPOSE: To examine the Consensus Model for APRN Regulation as a proposed solution to simplify and unify regulation of advanced nursing practice with respect to licensure, certification, accreditation, and educational standards. DATA SOURCES: Policy statements and reports issued by national organizations of nursing professionals and discussion within the scholarly literature provided an overview of regulatory differences among the 50 U.S. states, their impacts on advanced practice registered nurse (APRN) practice, and discussion of the Consensus Model as a potential solution. CONCLUSIONS: Major organizations of nursing professionals have endorsed the Consensus Model, indicating the importance of this significant step toward standards and consistent quality in APRN education and practice. Diverse regulatory criteria, such as variable accreditation standards, disparate certification and licensing requirements, inconsistent population foci, and scopes of practice, represent barriers to optimized APRN function within today's complex healthcare system and, ultimately, reduced access to safe, quality care for patients. IMPLICATIONS FOR PRACTICE: The Consensus Model for APRN Regulation promises to unify APRN education, practice, and licensure, promoting greater mobility among nursing professionals. Elimination of inconsistencies in APRN licensure, education, certification, and accreditation requirements will promote greater value and mobility for the APRN within the healthcare system. PMID- 24218236 TI - Patient comprehension of discharge instructions from the emergency department: a literature review. AB - PURPOSE: To examine research published from 1995 to 2010, evaluating patient comprehension of discharge instructions from emergency department (ED) or urgent care (UC) settings. Specifically, we examined: (a) the interventions utilized to provide discharge instructions, (b) the methods used to assess patient comprehension, and (c) the most effective strategies for assuring patient comprehension of ED discharge instructions. DATA SOURCES: A comprehensive literature review was conducted utilizing the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Reference Center Academic, Medline, Cochrane, and Ovid. English language peer-reviewed articles published between 1995 and 2010 were reviewed. Search terms included patient, comprehension, understanding, discharge instructions, health education, and emergency medicine. CONCLUSIONS: Increases in patient comprehension of ED discharge instructions are identified with alternative teaching interventions (multimedia) in comparison to traditional standardized written discharge instructions (usual care). Literature suggests clinicians seldom clarify patient comprehension in practice, though effective methods are noted in research. Future research is needed to explore innovative teaching interventions and their impact upon patient comprehension and patient outcomes. IMPLICATIONS FOR PRACTICE: To ensure patient comprehension of discharge instructions, the simplification of discharge material is paramount. Nurse practitioners working in ED or UC settings can improve upon "usual care" by exploring more innovative teaching interventions. PMID- 24218237 TI - Caring for military children in the 21st century. AB - PURPOSE: Civilian healthcare professionals provide approximately 2/3 of the healthcare for the 2 million U.S. military children. The President of the United States has made their care and support a top national security priority. The purpose of this article is to arm NPs with information necessary to care for the 21st century military child by providing current data on military family life, deployments, and the impact on children and their health-seeking behaviors. DATA SOURCES: Literature collected from sources identified through searches of PubMed, CINAHL, and PsycInfo covering the periods from 2003 to 2012. CONCLUSIONS: Military children are both resilient and vulnerable. While frequent moves build resilience, combat deployments increase the risk for abuse, neglect, attachment problems, and inadequate coping. The risk is highest right after the service member leaves for deployment and immediately upon return. Children's reactions to deployment differ by age, gender, and individual temperament. There is an 11% increase in outpatient visits for mental or behavioral health issues during deployment. IMPLICATIONS FOR PRACTICE: Healthcare professionals can support the physical and mental health of children by normalizing expectations and using the I CARE (Identify, Correlate, Ask, Ready Resources, Encourage) strategy to facilitate prevention and encourage early engagement with available resources. PMID- 24218238 TI - Centralized resources for nurse practitioners: common early experiences among leaders of six large health systems. AB - PURPOSE: This article describes common experiences of institutions that have pioneered the work of integrating nurse practitioners (NPs) into complex hospital environments and addresses effective strategies in achieving a centralized leadership model. DATA SOURCES: We conducted an informal, written survey and focus group discussions comparing experiences of leaders who were first in the position of centralizing resources and providing leadership for NPs in a hospital based setting. Experiences were compared and common practices summarized. CONCLUSIONS: The numbers of NPs required to provide patient care in an ever growing, complex hospital environment are increasing rapidly. To meet the professional needs of these hospital-based NPs, a strong centralized leadership approach should be utilized. An organized and centralized approach to credentialing, program development, orientation, and evaluation processes will become necessary as hospitals continue to hire increased numbers of NPs. IMPLICATIONS FOR PRACTICE: This article summarizes important considerations for formulating centralized leadership models for hospital-based NPs and provides a guide for administrators and NPs who are attempting to build similar models. PMID- 24218239 TI - Job satisfaction and perceived autonomy for nurse practitioners working in nurse managed health centers. AB - PURPOSE: More primary care providers are needed to deliver health care to Americans living in poverty and those soon to be insured under the Affordable Care Act. Nurse practitioners (NPs) in nurse-managed health centers (NMHCs) are poised to meet this need. This research study examined the characteristics of NPs working in NMHCs and measured job satisfaction and perceived level of autonomy. No studies about job satisfaction or autonomy for NPs working in NMHCs had been previously reported. DATA SOURCES: This descriptive, quantitative study surveyed primary care NPs working in NMHCs that are part of the National Nursing Centers Consortium (NNCC). NP e-mail addresses were obtained from NNCC center directors. Of 198 NPs invited to the electronic survey, 99 completed the Misener Nurse Practitioner Job Satisfaction Scale, demographic questionnaire, questions about perceived autonomy, and whether they would recommend working in an NMHC. Participants came from 16 states and 46 NMHCs. CONCLUSIONS: NPs working in NMHCs have job satisfaction, perceive their role as autonomous, and are satisfied with the autonomy they have. IMPLICATIONS FOR PRACTICE: NMHCs can provide access to primary health care for many Americans. More NPs may choose employment in NMHCs for job satisfaction and autonomy. PMID- 24218240 TI - Reading comprehension interventions for students with autism spectrum disorders: a synthesis of research. AB - The authors synthesized reading intervention studies conducted between 1980 and 2012 with K-12 students identified with autism spectrum disorders (ASD). Nine single-subject design studies, one quasi-experimental study, and two single-group design studies met the criteria for inclusion. Findings from the studies indicate that modifying instructional interventions associated with improved comprehension for students with reading difficulties may improve reading comprehension in students with ASD. Four studies implemented strategy instruction that included (a) question generation; (b) graphic organizers; and (c) making predictions. Two studies utilized anaphoric cueing instruction, three implemented explicit instruction, and three examined student grouping practices. Among the reviewed studies, the majority (n = 9) measured reading comprehension through researcher developed probes, and two studies reported results from standardized measures. PMID- 24218241 TI - Brief report: Arrested development of audiovisual speech perception in autism spectrum disorders. AB - Atypical communicative abilities are a core marker of Autism Spectrum Disorders (ASD). A number of studies have shown that, in addition to auditory comprehension differences, individuals with autism frequently show atypical responses to audiovisual speech, suggesting a multisensory contribution to these communicative differences from their typically developing peers. To shed light on possible differences in the maturation of audiovisual speech integration, we tested younger (ages 6-12) and older (ages 13-18) children with and without ASD on a task indexing such multisensory integration. To do this, we used the McGurk effect, in which the pairing of incongruent auditory and visual speech tokens typically results in the perception of a fused percept distinct from the auditory and visual signals, indicative of active integration of the two channels conveying speech information. Whereas little difference was seen in audiovisual speech processing (i.e., reports of McGurk fusion) between the younger ASD and TD groups, there was a significant difference at the older ages. While TD controls exhibited an increased rate of fusion (i.e., integration) with age, children with ASD failed to show this increase. These data suggest arrested development of audiovisual speech integration in ASD. The results are discussed in light of the extant literature and necessary next steps in research. PMID- 24218243 TI - Efficient electronic communication of two ruthenium centers through a rigid ditopic N-heterocyclic carbene linker. AB - A ditopic benzobis(carbene) ligand precursor was prepared that contained a chelating pyridyl moiety to ensure co-planarity of the carbene ligand and the coordination plane of a bound octahedral metal center. Bimetallic ruthenium complexes comprising this ditopic ligand [L4Ru-C,N-bbi-C,N-RuL4] were obtained by a transmetalation methodology (C,N-bbi-C,N=benzobis(N-pyridyl-N'-methyl imidazolylidene). The two metal centers are electronically decoupled when the ruthenium is in a pseudotetrahedral geometry imparted by a cymene spectator ligand (L4=[(cym)Cl]). Ligand exchange of the Cl(-)/cymene ligands for two bipyridine or four MeCN ligands induced a change of the coordination geometry to octahedral. As a consequence, the ruthenium centers, separated through space by more than 10 A, become electronically coupled, which is evidenced by two distinctly different metal-centered oxidation processes that are separated by 134 mV (L4=[(bpy)2]; bpy=2,2'-bipyridine) and 244 mV (L4=[(MeCN)4]), respectively. Hush analysis of the intervalence charge-transfer bands in the mixed-valent species indicates substantial valence delocalization in both complexes (delocalization parameter Gamma=0.41 and 0.37 in the bpy and MeCN complexes, respectively). Spectroelectrochemical measurements further indicated that the mixed-valent Ru(II)/Ru(III) species and the fully oxidized Ru(III)/Ru(III) complexes gradually decompose when bound to MeCN ligands, whereas the bpy spectators significantly enhance the stability. These results demonstrate the efficiency of carbenes and, in particular, of the bbi ligand scaffold for mediating electron transfer and for the fabrication of molecular redox switches. Moreover, the relevance of spectator ligands is emphasized for tailoring the degree of electronic communication through the benzobis(carbene) linker. PMID- 24218244 TI - Genetic strategies for dissecting complex traits in biomass willows (Salix spp.). AB - Willows are highly diverse catkin-bearing trees and shrubs of the genus Salix. They occur in many growth forms, from tall trees to creeping alpines, and successfully occupy a wide variety of ecological niches. Shrubby willows (sub genus Vetrix) have many characteristics that render them suited to cultivation in much faster growth cycles than conventional forestry. They respond well to coppicing, can be propagated vegetatively as cuttings and achieve rapid growth with low fertilizer inputs. As a result, willows grown as short rotation coppice are now among the leading commercially grown biomass crops in temperate regions. However, although willows have a long history of cultivation for traditional uses, their industrial use is relatively recent and, compared with major arable crops, they are largely undomesticated. Breeding programmes initiated to improve willow as a biomass crop achieved a doubling of yields within a period of <15 years. These advances were made by selecting for stem characteristics (height and diameter) and coppicing response (shoot number and shoot vigour), as well as resistance to pests, diseases and environmental stress, with little or no knowledge of the genetic basis of these traits. Genetics and genomics, combined with extensive phenotyping, have substantially improved our understanding of the basis of biomass traits in willow for more targeted breeding via marker-assisted selection. Here, we present the strategy we have adopted in which a genetic-based approach was used to dissect complex traits into more defined components for molecular breeding and gene discovery. PMID- 24218242 TI - Computational approaches to analyse and predict small molecule transport and distribution at cellular and subcellular levels. AB - Quantitative structure-activity relationship (QSAR) studies and mechanistic mathematical modeling approaches have been independently employed for analysing and predicting the transport and distribution of small molecule chemical agents in living organisms. Both of these computational approaches have been useful for interpreting experiments measuring the transport properties of small molecule chemical agents, in vitro and in vivo. Nevertheless, mechanistic cell-based pharmacokinetic models have been especially useful to guide the design of experiments probing the molecular pathways underlying small molecule transport phenomena. Unlike QSAR models, mechanistic models can be integrated from microscopic to macroscopic levels, to analyse the spatiotemporal dynamics of small molecule chemical agents from intracellular organelles to whole organs, well beyond the experiments and training data sets upon which the models are based. Based on differential equations, mechanistic models can also be integrated with other differential equations-based systems biology models of biochemical networks or signaling pathways. Although the origin and evolution of mathematical modeling approaches aimed at predicting drug transport and distribution has occurred independently from systems biology, we propose that the incorporation of mechanistic cell-based computational models of drug transport and distribution into a systems biology modeling framework is a logical next step for the advancement of systems pharmacology research. PMID- 24218246 TI - The complement system. Overview. PMID- 24218245 TI - The small RNA profile in latex from Hevea brasiliensis trees is affected by tapping panel dryness. AB - Natural rubber is harvested by tapping Hevea brasiliensis (Willd. ex A. Juss.) Mull. Arg. Harvesting stress can lead to tapping panel dryness (TPD). MicroRNAs (miRNAs) are induced by abiotic stress and regulate gene expression by targeting the cleavage or translational inhibition of target messenger RNAs. This study set out to sequence miRNAs expressed in latex cells and to identify TPD-related putative targets. Deep sequencing of small RNAs was carried out on latex from trees affected by TPD using Solexa technology. The most abundant small RNA class size was 21 nucleotides for TPD trees compared with 24 nucleotides in healthy trees. By combining the LeARN pipeline, data from the Plant MicroRNA database and Hevea EST sequences, we identified 19 additional conserved and four putative species-specific miRNA families not found in previous studies on rubber. The relative transcript abundance of the Hbpre-MIR159b gene increased with TPD. This study revealed a small RNA-specific signature of TPD-affected trees. Both RNA degradation and a shift in miRNA biogenesis are suggested to explain the general decline in small RNAs and, particularly, in miRNAs. PMID- 24218247 TI - Evaluation of complement function by ELISA. AB - Evaluation of total complement function in human serum is an essential component of laboratory diagnostics of the human complement system. During recent years, established hemolytic assays for classical pathway and alternative pathway function, CH50 and AP50 assays, respectively, have been replaced in many diagnostic laboratories by ELISA assays. Next to an improved standardization, this assay platform also allows for functional analysis of the lectin pathway of complement. The present chapter describes the methodology of ELISA assays for assessment of the classical pathway, the alternative pathway, the MBL-dependent lectin pathway, and the Ficolin-3-dependent lectin pathway of complement in clinical laboratory diagnostics. PMID- 24218248 TI - Classical complement pathway component C1q: purification of human C1q, isolation of C1q collagen-like and globular head fragments and production of recombinant C1q-derivatives. Functional characterization. AB - The classical complement pathway (CCP) activation is a multimolecular complex, composed of three subcomponents namely C1q, C1r, and C1s. C1q is the recognition subunit of this complex and its binding to the specific targets leads to the formation of active C1, which in turn activates the CCP in an immunoglobulin dependent or -independent manner. C1q is a hexameric glycoprotein composed of 18 polypeptide chains of three different types (A, B, and C), organized in two fragments-collagen-like (CLR) and globular head (gC1q) possessing different functional activity. The contemporary knowledge of the C1q structure allows the isolation and purification of a C1q molecule from serum by combination of different chromatography procedures including ion-exchange, size-exclusion, and affinity chromatography, as well as the isolation of CLR and gC1q by limited enzymatic hydrolysis of the native C1q molecule. In this chapter, we described methods for purification of human C1q and its CLR and gC1q fragments, as well as methods for their biochemical and functional characterization. The production and purification of recombinant C1q derivatives ghA, ghB, and ghC (globular fragments of the individual C1q chains) are also presented. PMID- 24218249 TI - Classical complement pathway components C1r and C1s: purification from human serum and in recombinant form and functional characterization. AB - C1r and C1s are the proteases responsible for the activation and proteolytic activity of the C1 complex of the classical complement pathway, respectively. They are assembled into a Ca(2+)-dependent C1s-C1r-C1r-C1s tetramer which in turn associates with the recognition protein C1q. The C1 complex circulates in serum as a zymogen and is activated upon binding of C1q to appropriate targets, such as antigen-antibody complexes. This property is used for the purification of C1r and C1s from human serum after binding of C1 to insoluble immune complexes. Disruption of the bound C1 complex by EDTA releases C1r and C1s which are further separated by ion-exchange chromatography; both proteins can be reassembled in the presence of calcium ions and the reconstituted tetramer isolated by gel filtration. In this chapter, we describe the purification of the activated and proenzyme forms of C1r and C1s and of the proenzyme C1s-C1r-C1r-C1s tetramer as well as methods for their biochemical and functional characterization. The production of recombinant C1s and of the proenzyme tetramer in a baculovirus insect cell system, and their purification by affinity chromatography is also presented. PMID- 24218250 TI - Expression and purification methods for the production of recombinant human complement component C2. AB - Human complement component C2 is a critical factor of the classical complement pathway. Here we provide a method for the production of recombinant human C2 (rhC2) protein for research purposes. The human complement component C2 (hC2) is cloned from a human cDNA library by polymerase chain reaction and inserted in a mammalian expression vector (Martini et al., BMC Immunol 11:43, 2010). Transient transfection is utilized to express hC2 in a mammalian cell line, and the expressed C2 is harvested from the conditioned media. rhC2 is purified from the conditioned media by sequential steps of cation exchange and affinity column chromatography. The purified hC2 is characterized for protein purity, stability, and enzymatic activity. The recombinant hC2 activity is tested in a complement activation ELISA assay that measures classical, alternative, and lectin complement pathway activity in C2-depleted serum. PMID- 24218251 TI - Purification and characterization of human and mouse complement C3. AB - Complement component C3 is the most abundant complement protein in plasma, central to all three complement activation pathways and essential to complement amplification. Thus, it is one of the most extensively studied complement proteins. This chapter describes the purification of C3 from human and mouse plasma using protein precipitation, followed by classical ion exchange chromatography and gel filtration. The biochemical and functional characteristics of the purified C3 are typically assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and hemolysis assays. The hemolysis assay is a standard technique to assess complement activity monitoring the lysis of red blood cells. PMID- 24218252 TI - Purification of human complement protein C5. AB - Complement C5 is cleaved by proteolysis in the terminal phase of complement activation generating the pro-inflammatory C5a and membrane attack complex nucleator C5b. Whereas purification of its paralogues C3 and C4 from plasma is relatively straightforward, C5 purification is more complicated due to the lower amounts present and overlaps with the much more abundant C3 during several chromatographic steps. Here we describe our procedure for purifying homogenous, monodisperse, and crystallizable C5. PMID- 24218253 TI - Quantification of complement C5b-9 binding to cells by flow cytometry. AB - Interaction of the complement system, directly or indirectly (e.g., via antibodies), with cells activates the early and late complement components and culminates in the deposition of a membrane-spanning C5b-9 complex on the cell surface. At a high copy number, this C5b-9 will activate cell death, whereas at a low copy number, it will transmit various signals into cells. Quantification of C5b-9 deposition is useful for assessments of the capacity of cells and antibodies to activate complement. By using an antibody that identifies a novel antigen of the C5b-9 complex, the amount of C5b-9 complexes on cells can be quantified by flow cytometry. The detailed protocol is described in this chapter. PMID- 24218254 TI - Challenges and opportunities in fractionation of recombinant human mannan-binding lectin. AB - Mannan-binding lectin is an oligomeric protein of the innate immune system. Both natural MBL as well as recombinant protein is a heterogeneous composition of oligomers containing from two up to at least eight structural units. Recombinant synthesis in mammalian cell lines often leads to a composition containing small oligomers not abundant in MBL from natural sources such as human plasma. Here, two procedures for fractionation of MBL oligomers are described. In one case, affinity chromatography is employed to enrich the abundance of large MBL oligomers to produce a composition of oligomers resembling natural MBL. In a second case, large-volume ion exchange chromatography is employed to separate these oligomers into fractions with an enhanced size homogeneity. Finally, a well established procedure for estimating the MBL protein concentration is detailed. PMID- 24218255 TI - Genotyping of FCN and MBL2 polymorphisms using pyrosequencing. AB - Pyrosequencing represents one of the most thorough methods used to analyze polymorphisms. One advantage of using pyrosequencing for genotyping is the ability to identify not only single-nucleotide polymorphisms (SNPs) but also tri allelic variations, insertions and deletions (InDels). In contrast to most other genotyping assays the sequence surrounding the polymorphism provides an internal control making this method highly reliable. PMID- 24218256 TI - Assay for estimation of the functional activity of the mannan-binding lectin pathway of the complement system. AB - Mannan-binding lectin (MBL) is a soluble pattern recognition molecule of the innate immune system. It is found in plasma in complex with MBL-associated serine proteases (MASPs). When MBL recognizes foreign, e.g., the surface of some microorganisms, or altered host surfaces the MASPs are activated and this will in turn lead to the initiation of the complement system, i.e., activation of complement by the MBL pathway. This will end up in increased phagocytosis of the microorganism and killing by insertion of pore structures in the membrane of the microorganisms. Lack of MBL seems significant in specific situations, e.g., in immunocompromised individuals were MBL is important in battling infections and, e.g., in ischemia/reperfusion injuries were MBL can have a negative inflammatory generating, and thus tissue destructive role, as it recognizes epitopes emerging in the ischemic tissue. It may thus be relevant in several situations to test for the presence of the MBL pathway in human sera. Here we describe a functional assay for estimation of MBL pathway activity by detection of complement factor deposition onto microtiter plate wells coated with a physiological relevant ligand for MBL. PMID- 24218257 TI - Purification, measurement of concentration, and functional complement assay of human ficolins. AB - Ficolins constitute a group of lectins involved in innate immunity. L-Ficolin, H ficolin, and M-ficolin are present in human serum. The human ficolins differ in carbohydrate-binding specificity, but they have in common the ability to recognize the acetyl group. L-Ficolin and H-ficolin are associated with serine proteases termed MASPs (MBL-associated serine proteases) and their truncated proteins, and the complexes (L/H-ficolin-MASP) activate the lectin pathway of complement upon binding to their ligands. Recombinant M-ficolin is also able to form a complex with MASP, resulting in complement activation. L-Ficolin and H ficolin can be purified as a complex with MASP from serum by utilizing their binding specificities. These ficolin-MASP complexes have an ability to activate C4. Human ficolins are quantified by ELISA using specific antibodies or ligands. PMID- 24218258 TI - Purification and functional analysis of human properdin. AB - Properdin is a member of the alternative pathway of complement. It is unique in that it is the only known positive regulator of the complement system. Properdin can stabilize and promote complement activation, but in addition is also capable of initiating the alternative pathway, making it a unique protein. This chapter focuses on the methods required for purifying human properdin and testing its functionality. PMID- 24218259 TI - Purification and functional characterization of C4b-binding protein (C4BP). AB - C4b-binding protein (C4BP) is a soluble, 570 kDa large glycoprotein, present in plasma at a concentration of approximately 200 mg/L. C4BP is the main inhibitor of the classical and lectin pathways of complement, where it controls C4b mediated reactions. Here, we describe a method for purification of C4BP from human plasma, which is based on barium chloride precipitation, anion exchange chromatography, and gel filtration. We also describe a functional assay, in which C4BP's cofactor activity to factor I, in the degradation of C4b, can be assessed. PMID- 24218260 TI - Purification and functional characterization of factor I. AB - Factor I (FI) is a soluble, 88 kDa glycoprotein present in plasma at a concentration of approximately 35 mg/L. FI inhibits all complement pathways as it degrades activated C4b and C3b when these are bound to a cofactor such as C4b binding protein or factor H. Here, we describe a method for purification of FI from human plasma, which is based on affinity chromatography followed by anion exchange chromatography. We also describe a functional assay, in which activity of FI can be assessed. PMID- 24218261 TI - C1 inhibitor: quantification and purification. AB - C1 inhibitor is a multipotent serpin capable of inhibiting the classical and the lectin pathways of complement, the fibrinolytic system, and contact/kinin system of coagulation. Deficiency of C1 inhibitor manifest as hereditary angioedema (HAE), an autosomal dominant hereditary disease. Measuring the C1 inhibitor level is of vital importance for the diagnosis of HAE and also for monitoring patients receiving C1 inhibitor for therapy. Determination of the antigenic C1 inhibitor level by the radial immunodiffusion (RID) technique is described in detail in this chapter. The presented purification method of plasma C1 inhibitor is primarily based on its high carbohydrate content and its affinity to the lectin jacalin. PMID- 24218262 TI - Purification, quantification, and functional analysis of Complement Factor H. AB - Complement Factor H (FH) is an abundant, non-enzymic plasma/serum glycoprotein, which has a major role in regulating activation of the complement system. It can be purified from human plasma/serum by affinity chromatography, using a monoclonal anti-FH antibody as ligand. Other affinity chromatography ligands, including cardiolipin and trinitrophenyl-bovine serum albumin (TNP-BSA), can be used to purify human FH and also FH from a wide range of vertebrates, including mammals, birds, bony fish. Human FH protein concentration can be quantified by sandwich ELISA. The activity of FH is generally measured by assays which detect the cleavage, by complement factor I, of the complement protein C3b to form iC3b. Cleavage occurs only in the presence of a cofactor, and FH is one of a small number of cofactors for this reaction. PMID- 24218263 TI - Factor H-related proteins. AB - Factor H-related proteins (CFHRs) are plasma glycoproteins related in structure and antigenicity to each other and to the complement inhibitory protein factor H. Such proteins are found in most mammals but their number and domain composition vary. This chapter summarizes our current knowledge on the human factor H-related proteins. In contrast to factor H, they have no strong complement inhibitory activity, although for some of them regulatory or complement modulatory activity has been reported. A common feature of CFHRs is that they bind to the C3b component of complement. Novel links between CFHRs and various diseases (C3 glomerulopathies, atypical hemolytic uremic syndrome and age-related macular degeneration) have been revealed in recent years, but we are still far from understanding their biological function. PMID- 24218264 TI - Functional evaluation of factor H genetic and acquired abnormalities: application for atypical hemolytic uremic syndrome (aHUS). AB - The atypical hemolytic uremic syndrome (aHUS) is a paradigm of a disease, caused by overactivation of the alternative complement pathway secondary to a not well understood trigger event. About 60 % of the patients present genetic or acquired abnormalities in the proteins of the alternative complement pathway. In 40 % of the cases the affected protein is the complement regulator Factor H (FH)-30 % due to mutations and 10 % because of anti-FH autoantibodies. Here we describe the detailed protocol for a rapid test to analyse the functional defect associated with genetic or acquired FH-related abnormalities. It can be applied for the characterization of the underlying complement defect in aHUS, based on spontaneous lysis of non-sensitized sheep erythrocytes in contact with patients' plasma or serum. PMID- 24218265 TI - Anti-factor H autoantibodies assay. AB - Non-Shiga-toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy which associates hemolytic anemia, thrombocytopenia, and acute renal failure. In 10 % of cases the disease is linked to presence of autoantibodies directed against Factor H (FH), the main plasmatic alternative complement pathway regulatory protein. Their presence induces an acquired functional FH deficiency. The anti-FH autoantibodies screening must be performed at the very onset of the disease in all cases of HUS, in order, first, to make the proper diagnosis as early as possible, and second to support an appropriate therapy including early plasma exchanges and immunosuppressive treatments. Thus, anti-CFH IgG represents a diagnostic marker and the titer determination is useful for assessing disease evolution, because changes precede clinical symptoms, and for monitoring of treatment. Presence of anti-FH IgG has been recently reported to be associated with other clinical context such as C3 glomerulopathies, but their pathogenicity in these conditions remains to be assessed. Here we describe the ELISA assay allowing the detection of these autoantibodies and report the analysis which can be performed concomitantly to improve the diagnosis. PMID- 24218266 TI - Purification of native surfactant protein SP-A from pooled amniotic fluid and bronchoalveolar lavage. AB - Surfactant protein SP-A is a hydrophilic glycoprotein, similar to SP-D, which plays an important role in pulmonary surfactant homeostasis and innate immunity. SP-A is actively expressed in the alveolar type II cells and Clara cells. Their basic structure consists of triple-helical collagen region and a C-terminal carbohydrate recognition domain (CRD). By binding to the infectious microbes, SP A (like SP-D) are involved in pathogen opsonization and agglutination and subsequent clearance of the microorganism, via recruitment of phagocytic cells via receptors for the collagen region. SP-A has also been localized at extra pulmonary sites such as salivary epithelium, amniotic fluid, prostate glands, and semen. The presence of SP-A in fetal and maternal tissue and amniotic fluid suggests it is involved in pregnancy and labor. Native SP-A can be purified from amniotic fluid and bronchiolar lavage fluid (BALF) via affinity chromatography. In addition, we also report here a procedure to express and purify a recombinant form of trimeric CRD in Escherichia coli. The availability of highly pure native SP-A and CRD region can be central to studies that examine the diverse roles that SP-A play in surfactant homeostasis, pulmonary infection and inflammation and pregnancy. PMID- 24218267 TI - Purification of surfactant protein D (SP-D) from pooled amniotic fluid and bronchoalveolar lavage. AB - Surfactant protein SP-D is a multimeric collagenous lectin, called collectin. SP D is a multifunctional, pattern recognition innate immune molecule, which binds in a calcium dependent manner to an array of carbohydrates and lipids, thus offering resistance to invading pathogens, allergen challenge, and pulmonary inflammation. SP-D is predominantly found in the endoplasmic reticulum of type 2 pneumocytes and in the secretory granules of Clara or non-ciliated bronchiolar cells. The highest expression of SP-D is observed in the distal airways and alveoli. There is also an extra pulmonary existence of SP-D. The common sources of native full-length human SP-D are bronchoalveolar lavage (BAL) washings from normal or preferably patients suffering from alveolar proteinosis who overproduce SP-D in the lungs. Amniotic fluid collected at the term during parturition is another reasonable source. Here, we describe a simple and rapid method of purifying native SP-D away from SP-A which is also present in the same source. We also describe procedures of expressing and purifying a recombinant fragment of human SP-D (rhSP-D) comprising trimeric neck and carbohydrate recognition domains that has been shown to have therapeutic effects in murine models of allergy and infection. PMID- 24218268 TI - Functional analysis of C5a effector responses in vitro and in vivo. AB - C5a is a powerful proinflammatory and immunomodulatory mediator as evidenced by its involvement in infectious, allergic, and autoimmune diseases as well as in cancer. C5a exerts most of its biologic functions through binding and activation of the G protein-coupled C5a receptor (C5aR). C5aR activation promotes complex signaling pathways eventually resulting in increased intracellular calcium (Ca(2+))i concentration. One of the prototypic effector functions associated with C5aR activation is the reconfiguration of the cell cytoskeleton resulting in increased cell motility and ligand-specific cell migration. Here, we describe three assays to assess C5a-mediated effector functions: (1) increase in (Ca(2+))i in bone marrow-derived neutrophils using the intracellular fluorescent Ca(2+) sensitive indicator Fluo-4 AM and flow cytometry-based methods; (2) in vitro migration of murine, bone marrow-derived neutrophils using a modified Boyden chamber; and (3) in vivo migration of neutrophils from the circulation into the peritoneal cavity. To control for the specificity of the C5a-mediated effects, C5aR-deficient mice, neutralizing C5aR-specific antibodies and potent pharmacologic C5aR inhibitors are available. PMID- 24218269 TI - Detection of complement receptors 1 and 2 on mouse splenic B cells using flow cytometry. AB - The complement receptor 2 (Cr2) gene is exclusively expressed in B cells and follicular dendritic cells (FDC) in mice and in humans. However, mice also express an alternative splice variant, CR1, of the Cr2 gene. CR2 and CR1 are receptors for the complement component 3 (C3) cleavage fragments C3d(g) and iC3b. Additionally, CR1 is a receptor for C3b and regulates complement convertase activity. CR1 and CR2 have various functions including antigen retention by FDC, regulation of surface complement convertases, and canonically as the B cell coreceptor in which CR2 acts to lower the threshold for B cell activation. Detection of CR1 and CR2 can be utilized to identify B cells and, depending on expression level, to delineate various B cell populations. This protocol describes methods for detecting CR1/2 expression on splenic B cell subsets via flow cytometry. PMID- 24218270 TI - Quantification of complement receptor 2 calcium signaling enhancement using flow cytometry. AB - The complement receptor 2 (Cr2) gene is exclusively expressed in B cells and follicular dendritic cells (FDC) in mice and in humans. CR2 is a receptor for the complement component 3 (C3) cleavage fragments C3d(g) and iC3b. On B cells CR2 acts as the B cell co-receptor in which ligand binding of CR2 effectively lowers the threshold for B cell activation. This protocol describes methods for the functional analysis of calcium signaling enhancement provided by CR2 co-receptor activity. PMID- 24218271 TI - Purification of C1q receptors and functional analysis. AB - The recognition subunit of C1, C1q, has emerged as an important player in various pathophysiologic conditions largely in part due to its ability to interact with pathogen-associated or cell surface expressed ligands and receptors. Identification and purification of these molecules is therefore of paramount importance if we are to procure valuable information with regards to the structure, function, and cell surface distribution. Since the interaction of C1q is better served when the receptors are purified from homologous species, we discuss here a simple guideline for the purification and characterization of the two C1q receptors, cC1qR (calreticulin) and gC1qR, from human cell lines. PMID- 24218272 TI - Detection of cell membrane-bound CD46 using flow cytometry. AB - CD46 is an important regulator of the complement system by preventing unwanted deposition of the complement activation products and opsonins C3b/C4b onto self tissue. Recently, intracellular signals mediated by CD46 activation on several distinct human cell types have demonstrated that CD46 also plays decisive roles in immuneregulation. The growing recognition of CD46 as key regulator in several vital biological processes, led to increased demand in sensitive methods for monitoring CD46 expression and changes thereof on cells and in tissues. Here we describe a method, which allows for studying CD46 expression on the surface of cells using specific antibodies in combination with fluorescence-activated cell sorting (FACS) analysis. PMID- 24218273 TI - Detection of CD59 using flow cytometry. AB - CD59 is the single regulator of the terminal complement pathway. It has been implicated in disease such as Paroxysmal nocturnal hemoglobinuria (PMH) and cancer. Expression of CD59 protects normal and malignant cells from the cytotoxic potential of the complement system. Here we describe a method, which allows for studying its expression on the surface of cells. PMID- 24218274 TI - Functional analysis of CD59 using complement-dependent cytotoxicity assay. AB - CD59 overexpression has been shown to confer the resistance of tumors to complement lysis. Complement lysis is one of the two major killing mechanisms of therapeutic anticancer antibodies. This chapter provides a method that allows studying the extent of complement protection of tumors by CD59. PMID- 24218275 TI - Detection of soluble CR3 (CD11b/CD18) by time-resolved immunofluorometry. AB - In the cell membrane complement receptor 3 (CR3) consists of one alpha chain (CD11b) and one beta chain (CD18). CR3 participates in many immunological processes, especially those involving cell migration, adhesion, and phagocytosis of complement-opsonized microbes. Recent findings of soluble CR3 in body fluids and in culture supernatant from experiments in vitro point to the involvement of ecto domain shedding as a part of the CR3 biology. To monitor such shedding on a quantitative basis, we have developed time-resolved immunofluorometric assays (TRIFMA) to detect soluble CD11b and CD18 in plasma or serum of either human or murine origin. Compared with most enzyme-linked immunosorbent assays methodologies, TRIFMA possesses prominent advantages, including better dynamic range and reproducibility. These assays may contribute to the understanding of the role of shedding of CR3 and other cell adhesion molecules in human disease and animal models involving inflammation. PMID- 24218276 TI - Analysis of the complement activation in mice. AB - Complement activation is an important immune mechanism in mice like in humans. Murine complement is also activated via three pathways, the classical, lectin, and alternative. Complement proteins are serine proteases; thus activation of complement is proteolytic cleavage of complement proteins, which are both soluble and deposited forms. Therefore, complement pathway activation can be assayed by measuring deposited cleaved complement proteins on materials that are known to activate each pathway. In this chapter, we describe how we assay activation of these three pathways in murine system. PMID- 24218277 TI - Opsonophagocytic assay. AB - The opsonophagocytic killing (OPK) assay is used as a correlate for protection to measure the functional capacities of vaccine-candidate-raised antibodies. This in vitro assay aids selecting promising vaccines by demonstrating whether the vaccine-induced antibodies drive efficient complement deposition and subsequent opsonophagocytic killing. Here, we describe two protocols for an OPK assay using either human-derived PMNs or cultured HL-60 cells. PMID- 24218278 TI - A cryogenically flexible covalent organic framework for efficient hydrogen isotope separation by quantum sieving. PMID- 24218279 TI - Efficacy of S-1 plus cisplatin combination chemotherapy in patients with HER2 positive advanced gastric cancer. AB - BACKGROUND: Combination chemotherapy with trastuzumab and cisplatin plus capecitabine or 5-fluorouracil has been used as a standard regimen for HER2 positive gastric cancer (GC) since the Trastuzumab for Gastric Cancer (ToGA) trial. Before the ToGA trial, HER2-positive GC in Japan was treated with S-1 plus cisplatin (SP). The primary objective of this retrospective study was to explore the efficacy of SP in HER2-positive GC. METHODS: We reviewed patients who had received SP as first-line chemotherapy at our institute between April 2007 and March 2011 and from whom we had enough samples to examine HER2 status. Seventy seven patients fulfilled the selection criteria and were tested for HER2 status with immunohistochemical staining (IHC) and fluorescence in situ hybridization. The patients' backgrounds were investigated to evaluate the clinicopathologic features of their HER2-positive GC, including survival. RESULTS: Seven (9.1 %) of 77 patients were judged to be IHC3+, and all of these had predominantly differentiated histology. HER2 positivity was associated with differentiated histology (P = 0.016) and liver metastasis (P = 0.025). Median overall survival was 23.6 months [95 % confidence interval (CI) 0.8-44.7] in HER2-positive GC and 12.9 months (95 % CI 8.3-17.5) in HER2-negative disease, but the difference was not statistically significant (P = 0.615). In multivariate analysis, HER2 status was not associated with survival outcomes. CONCLUSION: Because of the retrospective nature of this study, we cannot conclude whether HER2 status influences the survival of patients who receive SP as first-line chemotherapy. Our study provides important historical data for prospective phase II studies of SP plus trastuzumab. PMID- 24218280 TI - Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo embolization. AB - PURPOSE: The aim of the present study was to evaluate whether serum alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE). METHODS: We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE. RESULT: Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53 15.84, p < 0.0001), but not the AFP trend, as an independent prognostic factor for survival. While the AFP trend was correlated only with the overall response rate assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004). CONCLUSION: The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC. PMID- 24218281 TI - Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer. AB - BACKGROUND: The study populations of previous preoperative chemoradiotherapy (pre CRT) studies have consisted of mixed clinical stages, such as cT3-cT4 and/or cN positive. For this reason, it has not been possible to demonstrate whether pre CRT is of benefit for individual subgroups. METHODS: The medical records of 137 rectal cancer patients with clinical stage T3, N0 disease who received either pre CRT or postoperative chemoradiotherapy (post-CRT) between 2002 and 2011 were retrospectively analyzed. The regimen of pre-CRT consisted of slow fluorouracil (5FU) infusion and that of post-CRT consisted of bolus 5FU and leucovorin concurrent with radiation. RESULTS: Following pre-CRT, significant downstaging was achieved. However, administration of pre-CRT did not influence the type of surgical resection in tumours <=5 cm distant from the anal verge (p = 0.14). Pathological complete response was achieved in 16 % of the patients in the pre CRT group. The local recurrence rate (LRR) at 5 years was 5.7 % in the pre-CRT and 11.1 % in the post-CRT groups (p = 0.04). The distant recurrence rate (DRR) at 5 years was 76 % and 77 % in the pre-CRT and post-CRT groups, respectively (p = 0.1). Overall survival was similar in two groups (74.8 % vs. 75.3 %, p = 0.3). CONCLUSIONS: The treatment of stage T3, N0 rectal cancer patients with pre-CRT followed by surgery decreased LRR, but did not improve DRR or OS as compared with surgery followed by post-CRT in our patient cohort. PMID- 24218282 TI - Safety and effectiveness of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation. AB - BACKGROUND: Pathological diagnosis fails in some pulmonary tumors, although they may be highly suspected to be primary lung cancer. We studied the outcome of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation. METHODS: The current study included 37 patients (39 lesions) treated with stereotactic body radiotherapy who were clinically diagnosed with primary stage I lung cancer between August 1998 and April 2009 at our hospital. Pulmonary tumors were highly suspected to be malignant from physical and imaging examinations. Biopsies were performed for 62 % of patients, although malignancy was not pathologically confirmed. In the other 38 % of patients, a biopsy was not feasible. Median age of the patients was 77 years. Median tumor diameter was 20 mm. A total median dose of 48 Gy was prescribed to the isocenter in four fractions. Median follow-up period was 39 months. RESULTS: The 3-year overall survival, local control, and regional-distant control were 74.2, 94.0, and 68.6 %, respectively. In patients with tumors <=20 mm, overall survival and regional-distant control were significantly higher than in patients with tumors >20 mm (p <= 0.001), whereas no significant difference was observed regarding local control. No grade 3-5 adverse events possibly, probably, or definitely related to the treatment were observed. CONCLUSIONS: Stereotactic body radiotherapy is safe and effective for a clinically diagnosed primary stage I lung cancer when pathological diagnosis is difficult even with repeat biopsies, or a biopsy is not feasible for reasons of the patient's health condition or wishes. PMID- 24218283 TI - Tumor-suppressing effects of miR451 in human osteosarcoma. AB - Osteosarcoma is the 3rd most common human cancer in childhood and young adults, and is the leading cause of mortality. Recent studies suggest that miRNAs could regulate the growth and progression of osteosarcoma, indicating some novel targets for therapy. In our study, we demonstrated that miR-451 was down regulated in human osteosarcoma U2OS, SAOS, and MG63 cells lines as well as in tumor tissue surgically resected compared with the normal tissues. Overexpression of miR-451 inhibited cell proliferation and resulted in cell apoptosis in osteosarcoma cells. G1 cell cycle arrest was also induced by miR-451. Repressed by miR-451, PGE2 and CCND1 reversed the inhibitory effects of miR-451 on proliferation. In conclusion, miR-451 played a tumor-suppressing role through modulating the expression of PGE2 and CCND1, suggesting a novel target for the diagnosis and treatment of osteosarcoma. PMID- 24218284 TI - Endovascular recanalization of failed distal bypass in Buerger's disease. AB - In the treatment of Buerger's disease, bypass surgery with the use of an autologous vein has served as a treatment option in cases in which distal target vessel has been available. However, failed bypass occlusion can result in a devastating clinical scenario. Herein, we report a successful endovascular revascularization of failed distal bypass graft as a last resort for a patient with Burger's disease with ischemic rest pain and extensive tissue loss. PMID- 24218285 TI - Small needle puncture of a central venous occlusion in a hemodialysis patient that could not be traversed by a conventional technique. AB - A 75-year-old woman with hemodialysis-related right subclavian vein occlusion was referred to our hospital for retry of endovascular treatment. The occluded segment could not be crossed via either antegrade or retrograde approaches, including puncturing the obstruction with the stiff end of the guide wire. The obstruction was successfully punctured using a 75-cm long 21-G needle via the right median cubital vein and a metallic stent was placed to cover the occluded segment after balloon angioplasty. The recanalized segment was patent for 10 months until the patient's death from concomitant disease. PMID- 24218286 TI - Safety and efficacy of combined cyclophosphamide and rituximab treatment in recalcitrant childhood lupus. AB - To report the safety and efficacy of combined cyclophosphamide and rituximab treatment in Saudi children with systemic lupus erythematosus (SLE). Medical records of all children with SLE treated with cyclophosphamide and rituximab between June 2007 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh, were reviewed for demographic characteristics, age at diagnosis, concomitant treatments, indication of using rituximab and adverse events during the treatment period. Clinical and serologic response parameters included SLE Disease Activity Index (SLEDAI), complement, anti-ds DNA antibody and ANA levels, and mean daily corticosteroid dose assessed 3 months before combined cyclophosphamide and rituximab infusion course and at 6-month interval afterward. Sixteen patients (13 girls) with refractory SLE treated with cyclophosphamide and rituximab were included. The mean age at onset of SLE was 7.8 + 3.3 years, while the mean age at diagnosis was 8.1 + 3.4 years; the mean disease duration was 4.7 + 3.2 years. All patients were treated with corticosteroid and immunosuppressive drugs. Nephritis (8 patients) was the most frequent indication; other indications included refractory arthritis, thrombocytopenia, severe mucocutaneous lesions and central nervous system involvement. All patients received 2 doses, but 4 required 4-8 extra doses. All patients showed improvement in response parameters. There was significant reduction in SLEDAI (P < 0.0002) and corticosteroid dose (P < 0.005). A total of 4 adverse events were notified; 2 developed infusion-related reactions. One patient had severe soft tissue fungal infection, and other patient had pancreatitis. Our data showed beneficial therapeutic and steroid-sparing effects of rituximab as adjunctive treatment for children with refractory SLE including both renal and extrarenal manifestations. Although rituximab was well tolerated by the majority of patients, it may associated with various adverse events. PMID- 24218287 TI - A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer. AB - Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility. PMID- 24218288 TI - Minimal training is required to reliably perform quantitative ultrasound of muscle. AB - INTRODUCTION: Quantitative ultrasound can measure skeletal muscle pathology. We investigated whether inexperienced evaluators could accurately obtain and analyze ultrasound images. METHODS: Two examiners underwent a 20-minute training session before obtaining ultrasound images of several limb muscles in 21 healthy boys and 19 boys with Duchenne muscular dystrophy (DMD). Gray scale levels (GSLs) of muscle and subcutaneous fat were then measured by 2 analysts: a trained research assistant and a radiologist. We compared results between examiners and analysts. RESULTS: Interrater reliability of muscle GSLs was high between examiners (ICC >= 0.85) and analysts (ICC >= 0.84). As anticipated, GSLs were higher in dystrophic than in healthy muscles (P < 0.001). Fat GSLs were less reliable (ICC = 0.5-0.89) than muscle and increased with age and body size. CONCLUSIONS: GSLs from ultrasound images of healthy and dystrophic skeletal muscle, but not from subcutaneous fat, can be obtained reliably and can be analyzed by inexperienced evaluators with minimal training. PMID- 24218289 TI - Polycationic pillar[5]arene derivatives: interaction with DNA and biological applications. AB - Dendritic pillar[5]arene derivatives have been efficiently prepared by grafting dendrons with peripheral Boc-protected amine subunits onto a preconstructed pillar[5]arene scaffold. Upon cleavage of the Boc-protected groups, water-soluble pillar[5]arene derivatives with 20 (13) and 40 (14) peripheral ammonium groups have been obtained. The capability of these compounds to form stable nanoparticles with plasmid DNA has been demonstrated by gel electrophoresis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) investigations. Transfection efficiencies of the self-assembled 13/pCMV-Luc and 14/pCMV-Luc polyplexes have been evaluated in vitro with HeLa cells. The transfection efficiencies found for both compounds are good, and pillar[5]arenes 13 and 14 show very low toxicity if any. PMID- 24218290 TI - Binding of cyclic carboxylates to octa-acid deep-cavity cavitand. AB - As part of the fourth statistical assessment of modeling of proteins and ligands (sampl.eyesopen.com) prediction challenge, the strength of association of nine guests (1-9) binding to octa-acid host was determined by a combination of (1)H NMR and isothermal titration calorimetry. Association constants in sodium tetraborate buffered (pH 9.2) aqueous solution ranged from 5.39 * 10(2) M(-1) in the case of benzoate 1, up to 3.82 * 10(5) M(-1) for trans-4-methylcyclohexanoate 7. Overall, the free energy difference between the free energies of complexation of these weakest and strongest binding guests was DeltaDeltaG degrees = 3.88 kcal mol(-1). Based on a multitude of previous studies, the anticipated order of strength of binding was close to that which was actually obtained. However, the binding of guest 3 (4-ethylbenzoate) was considerably stronger than initially estimated. PMID- 24218292 TI - Sleep and adult neurogenesis: implications for cognition and mood. AB - The hippocampal dentate gyrus plays a critical role in learning and memory throughout life, in part by the integration of adult-born neurons into existing circuits. Neurogenesis in the adult hippocampus is regulated by numerous environmental, physiological, and behavioral factors known to affect learning and memory. Sleep is also important for learning and memory. Here we critically examine evidence from correlation, deprivation, and stimulation studies that sleep may be among those factors that regulate hippocampal neurogenesis. There is mixed evidence for correlations between sleep variables and rates of hippocampal cell proliferation across the day, the year, and the lifespan. There is modest evidence that periods of increased sleep are associated with increased cell proliferation or survival. There is strong evidence that disruptions of sleep exceeding 24 h, by total deprivation, selective REM sleep deprivation, and chronic restriction or fragmentation, significantly inhibit cell proliferation and in some cases neurogenesis. The mechanisms by which sleep disruption inhibits neurogenesis are not fully understood. Although sleep disruption procedures are typically at least mildly stressful, elevated adrenal corticosterone secretion is not necessary for this effect. However, procedures that prevent both elevated corticosterone and interleukin 1beta signaling have been found to block the effect of sleep deprivation on cell proliferation. This result suggests that sleep loss impairs hippocampal neurogenesis by the presence of wake-dependent factors, rather than by the absence of sleep-specific processes. This would weigh against a hypothesis that regulation of neurogenesis is a function of sleep. Nonetheless, impaired neurogenesis may underlie some of the memory and mood effects associated with acute and chronic sleep disruptions. PMID- 24218291 TI - Mutation effects of neuraminidases and their docking with ligands: a molecular dynamics and free energy calculation study. AB - A systematic study has been performed on neuraminidase (NA) mutations and NA inhibitor docked complexes, with the aim to understand protein-ligand interactions and design broad-spectrum antiviral drugs with minimal resistances. The catalytic D151 residue is likely to mutate while others are relatively conserved. The NA active-site conformations are altered by mutations, but more alterations do not necessarily result in larger deviations to the binding properties. The effects of all related mutations have been discussed; e.g., for the arginine triad (R118, R292 and R371), it is found that residue R118 plays the most significant role during ligand binding. Generally, the calculated binding free energies agree well with the experimental observations. Susceptibility of influenza virus to NA inhibitors can be reinforced by some mutations; e.g., the binding free energies of ligands with N2 subtype increase from -18.0 to -42.1 kcal mol(-1) by the E119D mutation. Mutations of the various NA subtypes often cause similar conformational and binding changes, explaining the occurrence of cross resistances; nonetheless, differences can be detected in some cases that correspond to subtype-specific resistances. For all NA subtypes, the electrostatic contributions are the major driving force for ligand binding and largely responsible for the binding differences between the wild-type and mutated NA proteins. PMID- 24218293 TI - A common origin for guanidinobutanoate starter units in antifungal natural products. AB - Keeping it basic: Arginine provides the exotic 4-guanidinobutanoate starter unit for two different types of zwitterionic polyketide (an example for one type is shown in the picture) produced by the same Streptomyces bacterium. The three-step precursor pathway is initiated by a remarkable decarboxylating monooxygenase with high specificity for arginine. PMID- 24218294 TI - Teaching primary care in pediatric outpatient department in developing countries: a feasibility study. AB - We studied the feasibility of teaching primary care to undergraduate medical students in an outpatient department (OPD) using a specially developed teaching package. Teaching was conducted in four 30 min sessions during a 4 week rotation term, and a test was offered at the end. We concluded, on the basis of grades achieved in the test, that it is feasible to impart primary care knowledge through OPD teaching using structured teaching goals for teachers. PMID- 24218295 TI - Immunoglobulin E-binding epitopes of mite allergens: from characterization to immunotherapy. AB - House dust mites and storage mites produce a number of allergens that can induce hypersensitivity reactions in humans and result in allergic diseases like asthma, rhinitis, and dermatitis. Recent advances in identifying and characterizing these allergens--and, in particular, their immunoglobulin E (IgE)-binding epitopes- have produced a wealth of knowledge. Here, methods for identifying IgE-binding epitopes, from immunoassays to in silico approaches, are summarized and placed in context with the identification of epitopes of mite allergens, particularly from the Dermatophagoides spp. major allergen groups 1 and 2. Finally, the transfer of this information to the clinical development and application of new diagnostic and immunotherapeutic approaches is discussed. While progress in recent years has built on the specific immunotherapies established decades ago, much work remains to be done to mitigate mite allergic disease. Future studies should seek to identify epitopes for mite species beyond Dermatophagoides and for minor allergens. Efforts in translational medicine should use the current epitope data to develop modified allergens for immunotherapy. PMID- 24218297 TI - Modulation of dual electronic circuits of [26]hexaphyrins using internal aromatic straps. AB - Internal bridges: [26]Hexaphyrins with an aromatic strap in 5,20 position have two potentially cyclic conjugated networks, that is, [18]porphyrin and [26]hexaphyrin, and show a formal analogy with [18]annuleno[18]annulens. 1,3 Phenylene-, 2,5-thienylene-, and 2,5-pyrrylene-bridged [26]hexaphyrins have been synthesized and characterized. PMID- 24218296 TI - Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes. AB - Despite almost universal implementation of renoprotective therapies over the past 25 years, the risk of end-stage renal disease (ESRD) in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of extensive studies that we have been conducting on the patients attending the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. The etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the loss of glomerular filtration rate, not reduction of albumin excretion rate, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better still, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD. PMID- 24218298 TI - Design of electrospayed non-spherical poly (L-lactide-co-glicolide) microdevices for sustained drug delivery. AB - Polymer chain entanglements in organic solvents can be considered a key parameter in the formation of non-spherical beads when electrospraying is employed. The shape of micro/nanometric drug delivery systems plays a major role since it can affect circulation, extravasation, distribution and in vivo clearance of the devices. In this frame, we investigated the influence of polymer processing parameters on the design of polylactic-co-glycolic acid non-spherical microdevices loaded with triamcinolone acetonide (TrA), a sparingly water soluble corticosteroid, prepared by electrospraying technique through a one-step process. In particular, we verified that the formation of non-spherical MDs is related to the presence of entanglements among polymer chains to select the optimal solution to be sprayed. The addition of TrA did not substantially affect the particle morphology in terms of size, size distribution and circularity at all the tested drug loadings. Furthermore, the drug could be released for a prolonged period, with controlled and reproducible kinetics for over 3 weeks. The mathematical modeling of release profiles highlighted that the release is mainly driven by degradation, at a higher extent in the case of low drug loading. PMID- 24218299 TI - (alpha'(H))-Dicalcium silicate bone cement doped with tricalcium phosphate: characterization, bioactivity and biocompatibility. AB - The influence of phosphorus doping on the properties of (alpha'(H))-dicalcium silicate (C(2)S) bone cement was analyzed, in addition to bioactivity and biocompatibility. All the cements were composed of a solid solution of TCP in C(2)S ([Formula: see text]-C(2)S(ss)) as the only phase present. The compressive strength ranged from 3.8-16.3 MPa. Final setting times ranged from 10 to 50 min and were lower for cements with lower L/P content. Calcium silicate hydrate was the principal phase formed during the hydration process of the cements. The cement exhibited a moderate degradation and could induce carbonated hydroxyapatite formation on its surface and into the pores. The cell attachment test showed that the (alpha'(H))-C(2)SiO(4) solid solution supported human adipose stem cells adhesion and spreading, and the cells established close contacts with the cement after 24 h of culture. The novel (alpha'(H))-C(2)S(ss) cements might be suitable for potential applications in the biomedical field, preferentially as materials for bone/dental repair. PMID- 24218300 TI - Influence of the chloride ion concentration on the corrosion of high-purity Mg, ZE41 and AZ91 in buffered Hank's solution. AB - This research studied the influence of the chloride ion concentration on the corrosion behaviour of high-purity magnesium (Mg) and two Mg alloys in Hank's solution, using hydrogen evolution and weight loss. A buffer based on CO2 and NaHCO3 was used to maintain the pH constant. The corrosion behaviour was governed by a partially protective surface film, and film breakdown by the chloride ions. The carbonated calcium phosphate layer that formed in Hank's solution was important in determining the protective properties of the surface film. PMID- 24218301 TI - Response to Comment on "Mechanism of Pt(IV) sonochemical reduction in formic acid media and pure water". PMID- 24218302 TI - Assessment of robustness against dissolved oxygen/substrate oscillations for C. glutamicum DM1933 in two-compartment bioreactor. AB - Corynebacterium glutamicum is an important organism for industrial biotechnology; particularly, in amino acid production (e.g. L-lysine). Production scales often reach reactor working volumes of several hundred cubic meters, which triggers inhomogeneous distribution of substrates and dissolved gasses due to increasing mixing times. Individual cells which follow the flow profile through the reactor are experiencing oscillating microenvironments. Oscillations can have an influence on the process performance, which is a subject of scale-down experiments. In this work, L-lysine-producing C. glutamicum DM1933 was assessed for its robustness against continuous dissolved oxygen and substrate supply oscillation in two-compartment scale-down bioreactors. Aerobic, substrate-limited stirred tank and non-aerated, substrate-excess plug flow compartments were applied for oscillation. Inhomogeneity of substrate and oxygen supply was observed to cause rapid side product turnover, redistribution of oxygen uptake from oxygen limited into fully aerobic zones, and intermediate medium acidification. However, process inhomogeneity did not impair productivity or growth at plug flow residence times of several minutes. In a focused analysis of proteome, metabolome, transcriptome, and other physiological parameters, no changes were identified in response to process inhomogeneity. In conclusion, fed batch processes with C. glutamicum DM1933 possess remarkable robustness against oxygen and substrate supply oscillation, which is a unique property in the field of published scale-down studies. Microbial physiology of C. glutamicum appears to be ideally adapted to both homogeneous and inhomogeneous conditions. This ensures exceptional suitability for cultivation at increased mixing times, which is suggested to constitute an important basis for the long-lasting success in large scale bioprocess application. PMID- 24218303 TI - Modeling hairy root tissue growth in in vitro environments using an agent-based, structured growth model. AB - An agent-based model for simulating the in vitro growth of Beta vulgaris hairy root cultures is described. The model fitting is based on experimental results and can be used as a virtual experimentator for root networks. It is implemented in the JAVA language and is designed to be easily modified to describe the growth of diverse biological root networks. The basic principles of the model are outlined, with descriptions of all of the relevant algorithms using the ODD protocol, and a case study is presented in which it is used to simulate the development of hairy root cultures of beetroot (Beta vulgaris) in a Petri dish. The model can predict various properties of the developing network, including the total root length, branching point distribution, segment distribution and secondary metabolite accumulation. It thus provides valuable information that can be used when optimizing cultivation parameters (e.g., medium composition) and the cultivation environment (e.g., the cultivation temperature) as well as how constructional parameters change the morphology of the root network. An image recognition solution was used to acquire experimental data that were used when fitting the model and to evaluate the agreement between the simulated results and practical experiments. Overall, the case study simulation closely reproduced experimental results for the cultures grown under equivalent conditions to those assumed in the simulation. A 3D-visualization solution was created to display the simulated results relating to the state of the root network and its environment (e.g., oxygen and nutrient levels). PMID- 24218304 TI - Hemospray treatment is effective for lower gastrointestinal bleeding. AB - Acute lower gastrointestinal bleeding (LGIB) is diverse in origin and can be substantial, requiring urgent hemostasis. Hemospray is a promising novel hemostatic agent for upper gastrointestinal bleeding (UGIB). It has been claimed in a small series that the use of Hemospray is also feasible in LGIB. We aimed to expand our knowledge of the application of Hemospray for the treatment of LGIB in a wider range of conditions to further define the optimal patient population for this new therapeutic modality. We analyzed the outcomes of nine unselected consecutive patients with active LGIB treated with Hemospray in two major hospitals in Europe. Initial hemostasis was achieved after Hemospray application in all patients. Rebleeding occurred in two patients (22%) who were on acetyl salicylic acid and presented with spurting bleeds. These preliminary data show that Hemospray can be effective in the management of LGIB, but suggest cautious use for patients on antithrombotic therapy and spurting bleeds. PMID- 24218305 TI - Commercially available biological mesh does not prevent stricture after esophageal mucosectomy. AB - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) offers a minimally invasive therapy for advanced esophageal dysplasia and early cancers but stricture formation limits its applicability. We aimed at assessing the efficacy of placement of a commercially available biological mesh for preventing stricture formation following esophageal EMR. METHODS: 25 swine were submitted to circumferential esophageal EMR with 10-cm extent and divided in five groups: one group with EMR only (control); one receiving an uncovered stent (stent-only group); and three groups receiving a stent covered with one of three extracellular matrices, namely small intestine submucosa (SIS group), acellular dermal matrix (ADM group), or urinary bladder matrix (UBM group). Stricture formation was evaluated with weekly esophagograms. RESULTS: The stent-only group had significantly less stricture formation and survival was extended compared with controls (4.8 vs. 2.4 weeks). Compared with stenting only, the addition of a biological mesh did not reduce stricture formation: percent reductions in esophageal diameter for the groups were SIS 86 %, ADM 94 %, and UBM 94 %, compared with 82 % in the stent-only group. CONCLUSIONS: Placement of commercially available biological meshes did not alter remodeling sufficiently to prevent stricture formation after esophageal EMR. PMID- 24218306 TI - Colonic diverticular hemorrhage: the hood method for detecting responsible diverticula and endoscopic band ligation for hemostasis. AB - BACKGROUND AND STUDY AIMS: Although colonic diverticular hemorrhage is a common cause of lower gastrointestinal bleeding, the low rate of detection of the diverticula responsible for bleeding, together with inadequate evaluation of endoscopic hemostasis, remain unsatisfactory. PATIENTS AND METHODS: Over 3 years, we employed the hood method to diagnose diverticular hemorrhage in 53 patients and applied endoscopic band ligation (EBL) for hemostasis in 27 patients with responsible diverticula. RESULTS: The hood method revealed active bleeding in 13 patients (24.5%), nonbleeding visible vessels in 14 patients (26.4%), and presumptive diverticular hemorrhage in 26 patients (49.1%). The nonbleeding visible vessels were located in the diverticular dome in 13 patients and at the diverticular orifice in one patient. EBL was performed in 27 patients, and a hemostasis rate of 96.3% was achieved. In 9 of 12 patients treated with EBL, follow-up colonoscopy revealed resolution of the responsible diverticula. CONCLUSIONS: The hood method improves the detection rate of diverticula responsible for bleeding by revealing potential nonbleeding visible vessels in the diverticular dome. EBL may become an effective procedure for hemostasis of colonic diverticular hemorrhage. PMID- 24218307 TI - A two-center randomized controlled trial of water-aided colonoscopy versus air insufflation colonoscopy. AB - BACKGROUND AND STUDY AIM: Water-aided colonoscopy includes water immersion and water exchange. Several small single-center studies have suggested that the use of water rather than air insufflation during colonoscopy reduces pain on insertion. The aim of this study was to investigate whether water-aided colonoscopy is less painful than air insufflation in a large cohort of patients. PATIENTS AND METHODS: This was a two-center, randomized controlled trial. Consecutive patients who agreed to start colonoscopy without premedication were included. Sedation was administered on demand. Water-aided colonoscopy was performed using water immersion in the early phase of the study, and subsequently water exchange was used. The primary endpoint was cecal intubation with pain scores of <= 2 and sedation with no or <= 2 mg midazolam. Secondary outcomes were pain score at discharge, cecal intubation rate and time, and adenoma detection rate (ADR). RESULTS: A total of 672 patients were randomized to water exchange (n = 338) or air insufflation (n = 334). The primary endpoint was achieved in more patients in the water exchange group (83.8 % vs. 62 %; P < 0.0005). On-demand sedation was also required less (11.5 % vs. 26.0 %; P < 0.0005) and mean pain score was lower (1.3 vs. 2.3; P < 0.0005) in the water exchange group. The cecal intubation rates were comparable. Water exchange had a significantly higher overall ADR (25.8 % vs. 19.1 %; P = 0.041), proximal ADR (10.1 % vs. 4.8 %; P = 0.014), and proximal < 10 mm ADR (7.7 % vs. 3.9 %; P = 0.046); proximal ADR was also higher in screening-only patients in the water exchange group (18.9 % vs. 7.4 %; P = 0.015). No detailed analysis was possible for the air insufflation vs. water immersion comparison. CONCLUSION: The current results confirmed that water exchange minimized the requirement for sedation and increased the ADR. PMID- 24218308 TI - Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified? AB - BACKGROUND AND STUDY AIMS: This study aimed to reassess whether the Forrest classification is still useful for the prediction of rebleeding and mortality in peptic ulcer bleedings and, based on this, whether the classification could be simplified. PATIENTS AND METHODS: Prospective registry data on peptic ulcer bleedings were collected and categorized according to the Forrest classification. The primary outcomes were 30-day rebleeding and all-cause mortality rates. Receiver operating characteristic curves were used to test whether simplification of the Forrest classification into high risk (Forrest Ia), increased risk (Forrest Ib-IIc), and low risk (Forrest III) classes could be an alternative to the original classification. RESULTS: In total, 397 patients were included, with 18 bleedings (4.5%) being classified as Forrest Ia, 73 (18.4%) as Forrest Ib, 86 (21.7%) as Forrest IIa, 32 (8.1%) as Forrest IIb, 59 (14.9%) as Forrest IIc, and 129 (32.5%) as Forrest III. Rebleeding occurred in 74 patients (18.6%). Rebleeding rates were highest in Forrest Ia peptic ulcers (59%). The odds ratios for rebleeding among Forrest Ib-IIc ulcers were similar. In subgroup analysis, predicting rebleeding using the Forrest classification was more reliable for gastric ulcers than for duodenal ulcers. The simplified Forrest classification had similar test characteristics to the original Forrest classification. CONCLUSION: The Forrest classification still has predictive value for rebleeding of peptic ulcers, especially for gastric ulcers; however, it does not predict mortality. Based on these results, a simplified Forrest classification is proposed. However, further studies are needed to validate these findings. PMID- 24218309 TI - Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors. AB - BACKGROUND AND STUDY AIM: Malignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS-FNA specimens, using resected specimens as the criterion standard. PATIENTS AND METHODS: A total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS-FNA specimens, and survival analysis based on EUS-FNA specimen grading. RESULTS: Intratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (P<0.001). Concordance rates for WHO classification between EUS-FNA and resected specimens were 74.0% using the mean Ki-67 index in EUS-FNA specimens and 77.8% using the highest Ki-67 index. The concordance rate rose to 90% when EUS-FNA samples with less than 2000 tumor cells were excluded (26% of EUS-FNA cases). The Kaplan-Meier survival curves were significantly stratified by the EUS-FNA grading of PNETs with 5-year survival rates of 100%, 58.3%, and 0%, for Grade 1, Grade 2, and neuroendocrine carcinoma (NEC) tumors, respectively. CONCLUSIONS: Grading of PNETs by the highest Ki-67 index in EUS-FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy. PMID- 24218310 TI - Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms. AB - BACKGROUND AND STUDY AIMS: Pancreatic ductal adenocarcinomas (PDAC) sometimes arise in patients with intraductal papillary mucinous neoplasms (IPMNs). This study examined the incidence of PDACs concomitant to or derived from branch duct IPMNs. The usefulness of endoscopic ultrasonography (EUS) relative to other imaging methods for detecting these tumors was also assessed. PATIENTS AND METHODS: This retrospective study used data from clinical records and imaging studies that were collected prospectively. During 2001-2009, 167 consecutive patients with IPMNs underwent EUS, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The 102 patients whose branch duct IPMNs lacked mural nodules/symptoms and thus did not qualify for resection were followed up by semiannual EUS and annual ultrasonography, CT, and MRI. The sensitivity and specificity with which the four modalities detected IPMN-derived and -concomitant PDACs at the first examination and throughout the study period were evaluated. The rate of PDAC development during follow-up was analyzed by the Kaplan-Meier method. RESULTS: A total of 17 IPMN-derived and 11 IPMN-concomitant PDACs were diagnosed at the first examination. Lesions that did not qualify for resection or chemotherapy were followed up for a median of 42 months. Seven IPMN-concomitant PDACs and no IPMN-derived PDACs were detected during follow-up. The 3- and 5-year rates of IPMN-concomitant PDAC development were 4.0% and 8.8%, respectively. At the first examination, EUS was superior to other imaging modalities in terms of IPMN-derived and -concomitant PDAC detection. Throughout the study period, including follow-up, EUS was significantly better at detecting IPMN-concomitant PDACs than the other modalities. CONCLUSIONS: IPMN-concomitant PDACs are quite often found at diagnosis and during follow-up. EUS examination of the whole pancreas plays an important role in the management of IPMNs as it allows the early detection of these small invasive carcinomas. PMID- 24218311 TI - Fine-needle tissue acquisition from subepithelial lesions using a forward-viewing linear echoendoscope. AB - BACKGROUND AND STUDY AIMS: The overall diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for subepithelial lesions (SELs) is suboptimal. The aim of this study was to evaluate the diagnostic accuracy, defined as the proportion of correct diagnoses, obtained using the EUS guided fine-needle tissue acquisition (FNTA) sampling technique performed with the newly developed forward-viewing EUS scope (FV-EUS). PATIENTS AND METHODS: This was a retrospective analysis of a prospectively collected database including all consecutive patients with SELs who underwent EUS-FNTA using the FV-EUS scope from 2007 to 2011 in a tertiary referral center. All procedures were performed by a single expert endoscopist. RESULTS: A total of 121 consecutive patients with SELs (13 in the esophagus, 96 in the stomach, 10 in the duodenum, 2 in the rectum) underwent sampling of the lesion using the FV-EUS scope. The procedure was technically feasible in all but one patient, and no complication related to EUS-FNTA occurred. Full histological assessment including immunostaining could be completed in 93.4% (113/121) of the patients. Considering neoplastic vs. non neoplastic diseases, the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 92.8% (95%CI 86.3-96.8), 100% (95%CI 69.0-100%), infinity, and 0.07 (95%CI 0.04-0.14), respectively. CONCLUSIONS: EUS-FNTA performed in conjunction with the FV-EUS scope for sampling SELs of the gastrointestinal tract was safe and provided a very high diagnostic accuracy. Studies comparing FV-EUS with standard curved linear echoendoscopes are needed to clarify whether these results are due to the sampling technique or the type of scope utilized. PMID- 24218312 TI - Entecavir-associated myopathy: a case report and literature review. AB - INTRODUCTION: Entecavir, a nucleoside analog (NA), is effective for treatment of chronic hepatitis B virus (HBV) infection. METHODS: We report the case of a patient we encountered with entecavir-associated myopathy. We also performed a literature review of myopathies associated with nucleoside analogs. RESULTS: A 44 year-old man presented with a 3-month history of myalgia and progressive weakness. He had HBV infection and had received entecavir antiviral treatment for 5 years. Laboratory tests showed that serum creatine kinase levels were significantly elevated. Muscle histopathology showed abundant T-lymphocyte infiltration of muscle fibers, and HBV surface antigen and HBV core antigen were not present in muscle fibers. Entecavir-associated myopathy was subsequently diagnosed. The patient's symptoms eventually resolved, and serum CK levels decreased rapidly after he stopped receiving entecavir treatments. CONCLUSIONS: Patients who receive NA therapy should be closely monitored for myopathic side effects. Muscle Nerve 49:610-614, 2014. PMID- 24218313 TI - Multiple Sclerosis International Federation: stimulating international cooperation in research. PMID- 24218314 TI - Unilateral leukonychia and hair depigmentation in multifocal motor neuropathy. AB - Neurophysiology studies in a 50-year-old man with slowly progressive weakness of the left upper limb revealed conduction block in the ulnar nerve above the elbow. His weakness remained stable with regular subcutaneous immunoglobulin, but he noted gradual hemibody hair depigmentation. Examination also revealed unilateral left hand leukonychia (figure). MRI of the brain and cervical spine was normal. PMID- 24218315 TI - Can outcomes in Duchenne muscular dystrophy be improved by public reporting of data? PMID- 24218316 TI - Carotid dissection following a generalized tonic-clonic seizure. PMID- 24218321 TI - Child Neurology: cognitive delay in a 7-year-old girl. AB - Organic acidurias are an important group of inherited metabolic disorders that affect the intermediary metabolic pathways of carbohydrate, amino acid, and fatty acid oxidation, leading to the accumulation of organic acids.(1) The 2 hydroxyglutaric acidurias are rare neurometabolic disorders characterized by developmental delay with or without other neurologic dysfunction. Three different subtypes have been described: d-2-hydroxyglutaric aciduria, l-2-hydroxyglutaric aciduria, and combined d-l-2-hydroxyglutaric aciduria. We describe the case of a child presenting with developmental delay who was found to have the classical biochemical, imaging, and genetic features of l-2-hydroxyglutaric aciduria. PMID- 24218322 TI - Teaching NeuroImages: neurodegeneration with brain iron accumulation in aceruloplasminemia. AB - A 55-year-old African Canadian man with insulin-dependent diabetes mellitus and alcohol abuse presented with diabetic ketoacidosis. Progressive cognitive decline over the previous 5 years resulted in long-term care placement. Aside from pigmentary retinopathy, general examination was unremarkable. MRI demonstrated iron accumulation in the brain (figure 1) and liver (figure 2A). Ceruloplasmin, a ferroxidase enzyme important in iron homeostasis, was undetectable and associated with low serum iron, low serum copper, and 10-fold increase in serum ferritin. Liver biopsy confirmed increased hepatocyte iron storage (figure 2B). Aceruloplasminemia was diagnosed.(1,2) Iron chelation was not administered given advanced dementia at presentation. PMID- 24218323 TI - Teaching NeuroImages: a neuroendocrine rarity: Wolfram syndrome. AB - Wolfram syndrome 1 (WS1) is an autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD syndrome). It is caused by a mutation in the WFS1 gene (chromosome 4p16.1, involved in regulation of intracellular calcium) that encodes wolframin, a transmembrane protein of pancreatic beta cells. WS1 is a rare disorder characterized by the development of insulin-dependent diabetes mellitus at an average age of 6 years, followed by optic atrophy (figure) at an average age of 11 and partial central diabetes insipidus and deafness in adolescence. Additional neurologic manifestations include truncal ataxia, myoclonus, epilepsy, nystagmus, and hyposmia.(1,2.) PMID- 24218325 TI - Interplay between cell growth and cell cycle in plants. AB - The growth of organs and whole plants depends on both cell growth and cell-cycle progression, but the interaction between both processes is poorly understood. In plants, the balance between growth and cell-cycle progression requires coordinated regulation of four different processes: macromolecular synthesis (cytoplasmic growth), turgor-driven cell-wall extension, mitotic cycle, and endocycle. Potential feedbacks between these processes include a cell-size checkpoint operating before DNA synthesis and a link between DNA contents and maximum cell size. In addition, key intercellular signals and growth regulatory genes appear to target at the same time cell-cycle and cell-growth functions. For example, auxin, gibberellin, and brassinosteroid all have parallel links to cell cycle progression (through S-phase Cyclin D-CDK and the anaphase-promoting complex) and cell-wall functions (through cell-wall extensibility or microtubule dynamics). Another intercellular signal mediated by microtubule dynamics is the mechanical stress caused by growth of interconnected cells. Superimposed on developmental controls, sugar signalling through the TOR pathway has recently emerged as a central control point linking cytoplasmic growth, cell-cycle and cell-wall functions. Recent progress in quantitative imaging and computational modelling will facilitate analysis of the multiple interconnections between plant cell growth and cell cycle and ultimately will be required for the predictive manipulation of plant growth. PMID- 24218324 TI - The role of reticulons in neurodegenerative diseases. AB - Reticulons (RTNs) are a group of membrane-associated proteins mainly responsible for shaping the tubular endoplasmic reticulum network, membrane trafficking, inhibition of axonal growth, and apoptosis. These proteins share a common sequence feature, the reticulon homology domain, which consists of paired hydrophobic stretches that are believed to induce membrane curvature by acting as a wedge in bilayer membranes. RTNs are ubiquitously expressed in all tissues, but each RTN member exhibits a unique expression pattern that prefers certain tissues or even cell types. Recently, accumulated evidence has suggested additional and unexpected roles for RTNs, including those on DNA binding, autophagy, and several inflammatory-related functions. These manifold actions of RTNs account for their ever-growing recognition of their involvement in neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia. This review summarizes the latest discoveries on RTNs in human pathophysiology, and the engagement of these in neurodegeneration, along with the implications of these findings for a better understanding of the molecular events triggered by RTNs and their potential exploitation as next-generation therapeutics. PMID- 24218326 TI - Arabidopsis thaliana mitogen-activated protein kinase 6 is involved in seed formation and modulation of primary and lateral root development. AB - Mitogen-activated protein kinase (MAPKs) cascades are signal transduction modules highly conserved in all eukaryotes regulating various aspects of plant biology, including stress responses and developmental programmes. In this study, we characterized the role of MAPK 6 (MPK6) in Arabidopsis embryo development and in post-embryonic root system architecture. We found that the mpk6 mutation caused altered embryo development giving rise to three seed phenotypes that, post germination, correlated with alterations in root architecture. In the smaller seed class, mutant seedlings failed to develop the primary root, possibly as a result of an earlier defect in the division of the hypophysis cell during embryo development, but they had the capacity to develop adventitious roots to complete their life cycle. In the larger class, the MPK6 loss of function did not cause any evident alteration in seed morphology, but the embryo and the mature seed were bigger than the wild type. Seedlings developed from these bigger seeds were characterized by a primary root longer than that of the wild type, accompanied by significantly increased lateral root initiation and more and longer root hairs. Apparently, the increment in primary root growth resulted from an enhanced cell production and cell elongation. Our data demonstrated that MPK6 plays an important role during embryo development and acts as a repressor of primary and lateral root development. PMID- 24218327 TI - Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield. AB - Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays AR GOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer's modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer's female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance. PMID- 24218329 TI - Polyamines and programmed cell death. AB - Polyamines (PAs) have been considered as important molecules for survival. However, evidence reinforces that PAs are also implicated, directly or indirectly, in pathways regulating programmed cell death (PCD). Direct correlation of PAs with cell death refers to their association with particular biological processes, and their physical contact with molecules or structures involved in cell death. Indirectly, PAs regulate PCD through their metabolic derivatives, such as catabolic and interconversion products. Cytotoxic products of PA metabolism are involved in PCD cascades, whereas it remains largely elusive how PAs directly control pathways leading to PCD. In this review, we present and compare advances in PA-dependent PCD in animals and plants. PMID- 24218328 TI - Perennially young: seed production and quality in controlled and natural populations of Cistus albidus reveal compensatory mechanisms that prevent senescence in terms of seed yield and viability. AB - The question of whether or not perennial plants senesce at the organism level remains unresolved. The aim of this study was to unravel whether or not plant age can influence the production and composition of seeds. Flower and seed production was examined in 3-, 8-, and 13-year-old Cistus albidus plants growing in experimental plots corresponding to the F2, F1, and F0 generations of the same population. Furthermore, the phytohormone, fatty acid, and vitamin E content of the seeds was evaluated, and their viability was examined. Whether or not age related differences in seed quality were observed in a natural population in the Montserrat Mountains (NE Spain) was also tested. The results indicate that under controlled conditions, the oldest plants not only produced fewer flowers, but also had higher rates of embryo abortion in mature seeds. However, germination capacity was not negatively affected by plant ageing. Seeds of the oldest plants contained significantly higher salicylic acid, jasmonic acid, and vitamin E levels compared with those from younger plants. Despite vigour (in terms of plant growth) being severely reduced due to harsh environmental conditions in the natural population, the oldest individuals produced seeds with no decline in viability. Seed biomass was instead positively correlated with seed viability. In conclusion, increased plant size may explain the loss of seed viability in the experimental field, but older smaller individuals in natural populations can escape senescence in terms of seed viability loss. PMID- 24218330 TI - TRV-GFP: a modified Tobacco rattle virus vector for efficient and visualizable analysis of gene function. AB - Virus-induced gene silencing (VIGS) is a useful tool for functional characterization of genes in plants. Unfortunately, the efficiency of infection by Tobacco rattle virus (TRV) is relatively low for some non-Solanaceae plants, which are economically important, such as rose (Rosa sp.). Here, to generate an easy traceable TRV vector, a green fluorescent protein (GFP) gene was tagged to the 3' terminus of the coat protein gene in the original TRV2 vector, and the silencing efficiency of the modified TRV-GFP vector was tested in several plants, including Nicotiana benthamiana, Arabidopsis thaliana, rose, strawberry (Fragaria ananassa), and chrysanthemum (Dendranthema grandiflorum). The results showed that the efficiency of infection by TRV-GFP was equal to that of the original TRV vector in each tested plant. Spread of the modified TRV virus was easy to monitor by using fluorescent microscopy and a hand-held UV lamp. When TRV-GFP was used to silence the endogenous phytoene desaturase (PDS) gene in rose cuttings and seedlings, the typical photobleached phenotype was observed in 75-80% plants which were identified as GFP positive by UV lamp. In addition, the abundance of GFP protein, which represented the concentration of TRV virus, was proved to correlate negatively with the level of the PDS gene, suggesting that GFP could be used as an indicator of the degree of silencing of a target gene. Taken together, this work provides a visualizable and efficient tool to predict positive gene silencing plants, which is valuable for research into gene function in plants, especially for non-Solanaceae plants. PMID- 24218331 TI - FLC-mediated flowering repression is positively regulated by sumoylation. AB - Flowering locus C (FLC), a floral repressor, is a critical factor for the transition from the vegetative to the reproductive phase. Here, the mechanisms regulating the activity and stability of the FLC protein were investigated. Bimolecular fluorescence complementation and in vitro pull-down analyses showed that FLC interacts with the E3 small ubiquitin-like modifier (SUMO) ligase AtSIZ1, suggesting that AtSIZ1 is an E3 SUMO ligase for FLC. In vitro sumoylation assays showed that FLC is modified by SUMO in the presence of SUMO-activating enzyme E1 and conjugating enzyme E2, but its sumoylation is inhibited by AtSIZ1. In transgenic plants, inducible AtSIZ1 overexpression led to an increase in the concentration of FLC and delayed the post-translational decay of FLC, indicating that AtSIZ1 stabilizes FLC through direct binding. Also, the flowering time in mutant FLC (K154R, a mutation of the sumoylation site)-overexpressing plants was comparable with that in the wild type, whereas flowering was considerably delayed in FLC-overexpressing plants, supporting the notion that sumoylation is an important mechanism for FLC function. The data indicate that the sumoylation of FLC is critical for its role in the control of flowering time and that AtSIZ1 positively regulates FLC-mediated floral suppression. PMID- 24218333 TI - Identification of new N-acylhomoserine lactone signalling compounds of Dinoroseobacter shibae DFL-12(T) by overexpression of luxI genes. AB - Bacteria of the Roseobacter clade are widespread in the ocean and occur in many different habitats. In the genome of Dinoroseobacter shibae DFL-12, luxI homologous genes that encode synthases responsible for the formation of N acylhomoserine lactones (AHLs) have been described. These compounds are known autoinducers that regulate several biological traits-namely, flagella formation and cell differentiation-in D. shibae through quorum sensing. The AHLs produced by D. shibae mainly consisted of N-octadecadienoylhomoserine lactone (C18:2-AHL) and N-octadecenoylhomoserine lactone (C18:1-HSL). In the wild type these AHLs are synthesized only in low abundance. The luxI genes were therefore expressed in Escherichia coli; this resulted in the formation of AHLs mostly different from those found in the D. shibae wild type. A luxI1 -deficient mutant of D. shibae was then reprovided with an overexpressed luxI1 gene. This strain produced large amounts of C18:2-AHL and C18:1-AHL, allowing full characterization of these compounds by mass spectrometric techniques and derivatization. Synthesis of the proposed structures confirmed that the major compound is (2E,11Z)-N-octadeca-2,11 dienoylhomoserine lactone (6, C18:2-HSL), accompanied by (Z)-N-octadec-11 enoylhomoserine lactone (5, C18:1-HSL). AHL 6 has not been reported before from other organisms and contains an unusual 2E double bond. PMID- 24218332 TI - Are interaural time and level differences represented by independent or integrated codes in the human auditory cortex? AB - Sound localization is important for orienting and focusing attention and for segregating sounds from different sources in the environment. In humans, horizontal sound localization mainly relies on interaural differences in sound arrival time and sound level. Despite their perceptual importance, the neural processing of interaural time and level differences (ITDs and ILDs) remains poorly understood. Animal studies suggest that, in the brainstem, ITDs and ILDs are processed independently by different specialized circuits. The aim of the current study was to investigate whether, at higher processing levels, they remain independent or are integrated into a common code of sound laterality. For that, we measured late auditory cortical potentials in response to changes in sound lateralization elicited by perceptually matched changes in ITD and/or ILD. The responses to the ITD and ILD changes exhibited significant morphological differences. At the same time, however, they originated from overlapping areas of the cortex and showed clear evidence for functional coupling. These results suggest that the auditory cortex contains an integrated code of sound laterality, but also retains independent information about ITD and ILD cues. This cue-related information might be used to assess how consistent the cues are, and thus, how likely they would have arisen from the same source. PMID- 24218334 TI - Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population. AB - We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case-control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR = 1.69, 95 % CI = 1.15-2.49) and rs3748067 TT (adjusted OR = 1.73, 95 % CI = 1.03-2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR = 2.48, 95 % CI = 1.49 4.12) and rs3748067 TT (adjusted OR = 2.54, 95 % CI = 1.34-5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR = 2.09, 95 % CI = 1.25-3.45) and rs3748067 TT (adjusted OR = 2.29, 95 % CI = 1.20-4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer. PMID- 24218335 TI - Bufalin exerts antitumor effects by inducing cell cycle arrest and triggering apoptosis in pancreatic cancer cells. AB - As one of the most aggressive human malignancies, pancreatic cancer is a leading cause of cancer-related deaths worldwide and only about 4% of patients will live 5 years after diagnosis. Eighty to approximately eighty-five percent of patients are diagnosed with an unresectable or metastatic disease, which is correlated with poor prognosis and low survival rate. Therefore, it is tremendously significant to exploit novel chemicals to prevent and treat pancreatic cancer. Previous research and clinical studies have demonstrated that many natural products derived from traditional Chinese medicine (TCM) such as camptothecin derivatives and vinca alkaloids could be effective antitumor compounds, hinting that TCM is a promising source for developing new antitumor drugs. In this report, we investigated the effects of bufalin, a primary active ingredient of the traditional Chinese medicine Chan-Su, on pancreatic cancer cell lines PANC-1 and CFPAC-1 and studied the underlying molecular mechanism. We found that exposure to bufalin could suppress the proliferation of pancreatic cancer cells time and dose dependently. We used flow cytometry to study the effects of bufalin on apoptosis and cell cycle distribution in PANC-1 and CFPAC-1 cells. The results indicated that bufalin could significantly induce both apoptosis and G2/M cell cycle arrest in pancreatic cancer cells. With western blotting, we found that the expression level of an antiapoptotic protein heat shock protein 27 (Hsp27) and its partner molecule p-Akt was decreased upon the treatment with bufalin. Besides, bufalin activated pro-caspase-3 and pro-caspase-9 and modulated the expression level of Bcl-2 and Bax. These data suggested that bufalin may trigger apoptosis by targeting Hsp27, which could inhibit apoptosis by interfering with key apoptotic proteins. The influence on the level of cylinB1, CDK1, and p21 was also observed after bufalin treatment, and the relationship between Hsp27 and the cell cycle-related proteins mentioned above deserves much more research. In addition, our data showed that bufalin could enhance the growth inhibition effect of gemcitabine in above pancreatic cancer cells. Taken together, bufalin might be worthy of further study for its potential as a therapeutic agent for pancreatic cancer treatment. PMID- 24218336 TI - Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis. AB - Increasing scientific evidences suggest that circulating tumor cells (CTC) in peripheral blood may be a powerful predictor of survival in patients with pancreatic cancer. However, many existing studies have yielded inconclusive results. This meta-analysis aims to assess the prognostic value of CTC in patients with pancreatic cancer. An extensive literary search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI, and CBM databases from their inception through July 1, 2013. The meta-analysis was then performed using the Stata 12.0 software. Crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated under a fixed or random effect model. Nine cohort studies were included in this meta-analysis with a total of 623 pancreatic cancer patients. This number included 268 CTC-positive patients and 355 CTC-negative patients. Our meta-analysis revealed that patients in the CTC-positive group were significantly associated with poor progression-free survival (PFS) (HR = 1.89, 95% CI = 1.25 4.00, P < 0.001). Furthermore, pancreatic cancer patients in the CTC-positive group also showed worse overall survival (OS) than those in the CTC-negative group (HR = 1.23, 95% CI = 0.88-2.08, P < 0.001). Subgroup analysis by ethnicity indicated that CTC-positive patients had poor OS among both Asian and Caucasian populations (all P < 0.05). Further subgroup analyses by detection and treatment methods also suggested that CTC-positive patients showed worser OS than CTC negative patients in the majority of subgroups (all P < 0.05). No publication bias was detected in this meta-analysis. In conclusion, our meta-analysis suggests that CTC-positive pancreatic cancer patients may have worser PFS and OS than CTC-negative patients. Detection of CTC in peripheral blood may be a promising biomarker for the detection and prognosis of pancreatic cancer. PMID- 24218337 TI - MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. AB - MicroRNAs (miRNAs) are small non-protein-coding RNAs that regulate expression of a wide variety of genes including those involved in cancer development. Here, we investigate the role of miR-143 in breast cancer. In this study, we showed that miR-143 was frequently downregulated in 80% of breast carcinoma tissues compared to their adjacent noncancerous tissues. Ectopic expression of miR-143 inhibited proliferation and soft agar colony formation of breast cancer cells and also downregulated DNA methyltransferase 3A (DNMT3A) expression on both mRNA and protein levels. Restoration of miR-143 expression in breast cancer cells reduces PTEN hypermethylation and increases TNFRSF10C methylation. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Furthermore, miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in breast cancer tissues. Our findings suggest that miR-143 regulates DNMT3A in breast cancer cells. These findings elucidated a tumor-suppressive role of miR-143 in epigenetic aberration of breast cancer, providing a potential development of miRNA-based treatment for breast cancer. PMID- 24218338 TI - Overexpression of stathmin 1 confers an independent prognostic indicator in nasopharyngeal carcinoma. AB - Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p = 0.027), higher T stage (p = 0.003), and overall clinical stage (p = 0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.001), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation. PMID- 24218339 TI - Association between IL-4 -589C>T polymorphism and colorectal cancer risk. AB - In order to make a comprehensive assessment of the potential association between interleukin-4 (IL-4) -589C>T and colorectal cancer (CRC) susceptibility, we conducted a meta-analysis of six epidemiological studies, which included 1,317 CRC patients and 1,659 controls. The data showed that IL-4 -589C>T was not associated with increased CRC risk in the overall population. In the subgroup analysis of IL-4 -589C>T, the results did not change when the analyses were restricted to race. Based on this meta-analysis, we conclude that IL-4 -589C>T may be not a risk factor for CRC development. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on CRC. PMID- 24218340 TI - Absent expression of FLNA is correlated with poor prognosis of nasopharyngeal cancer. AB - This study aimed to analyze the expression, clinical significance of filamin A (FLNA) in nasopharyngeal carcinoma, and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 63 cases of nasopharyngeal cancer and 21 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into nasopharyngeal cancer CNE2 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, migration, and invasion assays were also conducted as to the influence of the upregulated expression of FLNA that might be found on CNE2 cell biological effect. Immunohistochemistry: the level of FLNA protein expression was found to be significantly lower in nasopharyngeal cancer tissue than normal tissues (P < 0.05). Western blot: the relative amount of FLNA protein in nasopharyngeal cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was correlated with T stages, lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan Meier analysis (P < 0.05). The result of biological function has shown that CNE2 cell-transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with CNE2 cell-untransfected FLNA (P < 0.05). FLNA expression decreased in nasopharyngeal cancer and correlated significantly lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play important roles as a negative regulator to nasopharyngeal cancer CNE2 cell by promoting degradation of MMP-9. PMID- 24218341 TI - Full sensitivity and enhanced resolution in homodecoupled band-selective NMR experiments. PMID- 24218342 TI - Factor-Xa inhibitors protect against systemic oxidant damage induced by peripheral-ischemia reperfusion. AB - Factor-Xa inhibitors are often used for prophylaxis and for the treatment of thrombotic vascular disorders. However, it is not known whether they are beneficial during the recanalization of the thrombotic vascular segment and during tissue reperfusion. Herein, we describe an animal study that was designed to investigate the possible protective effects and antioxidant properties of factor-Xa inhibitors. Forty rats were included in the study and were randomly divided into five equal groups. The first group served as a control group from which we obtained basal oxidant and antioxidant parameters. Peripheral ischemia was induced in the second group (sham group) for 6 h, and plasma levels of nitrogen oxide (NOx), prolidase and malondialdehyde (MDA) were obtained after 30 min of reperfusion. The sham group did not receive any drugs. Oral rivaroxaban (3 mg/kg) was administrated to Group III, intraperitoneal enoxaparin sodium (250 U/kg) was administrated to Group IV, and intraperitoneal bemiparine sodium (250 U/kg) was administrated to Group V 1 week prior to the induction of peripheral ischemia (for 6 h)-reperfusion. After 30 min of reperfusion, blood samples were obtained and NOx, prolidase and MDA levels in these groups were detected, and the rats were sacrificed. NOx levels were statistically similar (p > 0.05) between Groups I, II, III, IV, and V (20.7 +/- 10.4, 17.4 +/- 9.7, 25.9 +/- 24.2, 27.0 +/ 11.9, 23.3 +/- 17.3 MUmol/L, respectively). MDA levels were significantly lower (p < 0.05) in Groups III (rivaroxaban), IV (enoxaparin sodium), and V (bemiparine sodium) (24.9 +/- 11.9, 25.9 +/- 4.4, 25.4 +/- 10.8 MUmol/L, respectively) when compared with the sham group (Group II) (75.6 +/- 24.3 MUmol/L). Prolidase levels were higher (p > 0.05) in the ischemia reperfusion groups (659.2 +/- 130.6 in II (sham), 1,741.0 +/- 1,530.6 in III (rivaroxaban), 2,453.8 +/- 1,590.4 in IV (enoxaparin sodium), and 889.2 +/- 574.7 U/g in V (bemiparine sodium) than in the control group (144.6 +/- 131.8 U/g). Ischemia-reperfusion events may occur in prothrombotic disorders. During these events, prophylactic or therapeutic factor Xa inhibitors can protect against thrombosis and oxidative reperfusion injury. The new oral factor-Xa inhibitor, rivaroxaban, appears to provide the same antioxidant support as injectable low molecular weight heparins (LMWHs). PMID- 24218343 TI - Epicardial fat: more than just an "epi" phenomenon? AB - Regional body-fat distribution is one of the key variables that explains the metabolic heterogeneity of obesity and its related cardiovascular risks. According to the ectopy concept, the inability of subcutaneous adipose tissue to store surplus triglycerides may lead to the development of fat in ectopic sites, such as the heart. Epicardial adipose tissue is a metabolically active endocrine organ that produces numerous factors that can modulate cardiac structure and function. The development of in vivo noninvasive imaging has made it possible to quantify its thickness and volume with increasing accuracy. In this review, we discuss the local interaction and cross-talk between epicardial fat and neighboring structures, such as coronary arteries and myocardium, and its relevance to cardiac diseases, such as coronary-artery disease or atrial fibrillation. Beneficial and harmful effects of epicardial adipose tissue are described and analyzed. What leads to an imbalance between protective and deleterious actions has to be further explored. We believe that epicardial fat, which has been neglected for years, plays a key role in cardiovascular disease pathophysiology and represents a "new world" exploration for therapeutic targets, which will be addressed in future clinical and research studies. Elucidating the mechanisms that drive the deposition or mobilization of cardiac adiposity between other ectopic-fat stores needs to be accomplished within the next few years. PMID- 24218344 TI - Acute and chronic effects of botulinum neurotoxin a on the mammalian neuromuscular junction. AB - INTRODUCTION: Botulinum neurotoxin A (BoNT/A) cleaves SNAP-25 and inhibits acetylcholine (ACh) release at the neuromuscular junctions (NMJ) to cause neuroparalysis. Previous reports indicate a dyssynchrony between the inhibitory effect of BoNT/A on ACh release and SNAP-25 cleavage. METHODS: We tested the in vitro (acute; 90 min) and in vivo (chronic; 12 h) effects of BoNT/A on stimulus evoked ACh release (SEAR), twitch tension, and SNAP-25 cleavage in isolated extensor digitorum longus (EDL) nerve-muscle preparations (NMP). RESULTS: In vitro or in vivo BoNT/A poisoning inhibited SEAR and twitch tension. Conversely, SNAP-25 cleavage and inhibition of spontaneous release frequency were observed only in NMP poisoned with BoNT/A in vivo. Moreover, chronic treatment of BoNT/A inhibited ionomycin stimulated Ca(2+) signals in Neuro 2a cells. CONCLUSIONS: These results demonstrate that the inhibition of SEAR precedes SNAP-25 cleavage and suggest involvement of a more complex mechanism for the inhibitory effect of BoNT/A at the NMJ. PMID- 24218345 TI - Audit of a state-wide store and forward teledermatology service in Australia. AB - In 2008, the Skin Emergency Telemedicine Service was established at the Princess Alexandra Hospital (PAH) in Brisbane. We conducted an audit by evaluating all email communication during 2012, and administering a clinician questionnaire. A total of 167 cases were discussed via 685 email communications (46 being in-house PAH referrals). The highest number of external referrals came from Mt Isa (27%), located 1200 km from the nearest dermatology clinic, with a further 25% sent from centres located 50-600 km from a clinic. The main referring condition was rash (65%), followed by skin lesions (13%). The most commonly provided telemedicine diagnoses were dermatitis/eczema (23%), infection (20%) and drug eruption (17%). Most external referrals received a reply within 3 hours of the enquiry. Junior doctors (2nd-4th postgraduate year) represented the majority of referring clinicians (62% of questionnaire respondents). There were 111 potential questionnaire recipients. Responses were received from 34 clinicians, a response rate of 31%. Overall 100% of respondents stated that the service was useful to them and 97% said they would use it again in the future with one respondent stating 'possibly'. It seems likely that teledermatology will serve an important role in the provision of healthcare to Queensland, and other remote Australian communities in the future. PMID- 24218346 TI - Internet video to support intravenous medication administration in the home: a cost minimisation study. AB - We compared the costs associated with three different methods of administering antibiotics to paediatric oncology patients. In scenario A, medicine was prepared in the home, checked in the home using a video link to a second nurse, and administered in the home. In scenario B, medicine was prepared by outsourcing the work to a commercial organisation, checked by pharmacists off-site and administered in the home. In scenario C, medicine was prepared in the hospital, checked by a second nurse and administered in the outpatient department. The staff time required for home administration was calculated from actual home visits. The cost of tablet computers and mobile Internet charges for double checks in the home was based on an assumed useful life of 3 years for the equipment. The cost of outsourcing the preparation of medications was calculated from the actual cost of doing so during a four month period. Patient outcome was assumed to be the same in all three scenarios. The mean costs of a medication episode (i.e. one occasion of medication administration) was $129.91 in scenario A, $312.00 in scenario B and $355.91 in scenario C. Nurse preparation and administration in the home would save the oncology health service $124,899 per annum compared to outsourcing medication preparation. Nurse preparation and administration in the home would save the oncology health service $155,329 per annum compared to nurse preparation and administration in the outpatient department. Use of Internet-based video appears to produce savings compared to other methods of administering antibiotics and the technique may have wider application in supporting complex interventions in the home. PMID- 24218347 TI - A qualitative case study of telehealth for in-home monitoring to support the management of type 2 diabetes. AB - The present study formed part of a randomised controlled trial of telehealth for in-home monitoring to support people with poorly controlled type 2 diabetes. We explored the experiences of patients and healthcare practitioners, and their perceptions of the telehealth model of care used in the trial. In addition to their usual diabetes care, participants receive diabetes care from a diabetes educator nurse via an in-home broadband communication device. On average, each patient participated in 14 videoconferences with a diabetes care coordinator during the 12-month trial period. Qualitative data was collected from two general practices and included semi-structured interviews and document review of patient clinical notes. A total of 12 people were interviewed: 8 health practitioners and 4 patients. Patients and health practitioners expressed a high level of satisfaction with the model of care provided. Patients also reported positive health and social outcomes as a result of being involved in the trial and indicated that in the main they had achieved their goals and were happy with their progress over the 12-month period. Analysis of interviews revealed three broad elements associated with the implementation of telehealth: interpersonal factors, operational problems and the wider health system context within which the general practices and trial team were operating. The findings suggest that adopting telehealth in the management of type 2 diabetes can lead to improved diabetes control, but more support is required to ensure sustainability and widespread implementation. PMID- 24218348 TI - A qualitative study of the use of Skype for psychotherapy consultations in the Ukraine. AB - There has been rather limited use of Skype for health and medical purposes. We investigated the use of Skype for delivering psychotherapy services in the Ukraine. A provider questionnaire was distributed to all delegates (n = 50) at the Annual Symposium of Psychotherapists. One copy of a client questionnaire was also given to each service provider and they were instructed to request their next client to complete the survey. In total, 29 providers and 23 clients responded to the questionnaire. The majority of clients (61%) and providers (72%) had used Skype for a range of services. The services they provided were related to a wide range of paradigms including psycho-analysis, psycho-drama, Gestalt therapy, cognitive behavioural therapy and existential therapy. A key reason for using Skype was to allow practitioners to contact clients who were not easily accessible, e.g. those who lived in other countries. Most practitioners (n = 24) thought their clients considered the services received on Skype were good or excellent. All 26 practitioners charged for Skype consultations. The majority of clients and providers showed high satisfaction with the use of Skype for psychotherapy services. PMID- 24218349 TI - Telemedicine for clinical management of diabetes - a process analysis of video consultations. AB - We analysed 56 video consultations provided in a 5-month period by two endocrinologists from the tele-endocrinology clinic of a tertiary teaching hospital in Brisbane. The patients were suffering from type 1 or type 2 diabetes, and 41% of them had at least one diabetic complication. Their mean age was 51 years and 45% were female. The consultations were provided to ten cities located 210-1800 km from Brisbane. A questionnaire was developed for analysing the video visits. It comprised 26 questions, arranged in six sections: (1) Patient characteristics, (2) Reason for referral, (3) Procedures and findings, (4) Recommendations, (5) Telehealth logistics, (6) Consultant's opinion. In 66% of consultations a nurse accompanied the patient. The specialist requested the nurse to perform a physical examination in 18% of these cases. No change in medications was made in 36% of the consultations. The most frequent recommendations were requesting laboratory tests (75%), insulin dose adjustments (39%) and referrals to an allied health professional (13%). Out of 56 consultations, the specialists indicated the need to perform a physical examination for 12 patients that was not possible remotely. However, they requested an in-person (face-to-face) visit for three patients. Nevertheless they believed that in 34% of the cases they could have made a better decision if the consultation had been in-person. Video consultation can substitute for a large proportion of in-person specialist consultations for people with diabetes who are referred to endocrinology specialists. PMID- 24218350 TI - The introduction of web-based video-consultation in a paediatric acute care setting. AB - The Royal Children's Hospital (RCH) in Melbourne has been providing web-based video-consultations for a range of paediatric sub-specialties since 2011. There were 346 video-consultations in the first 16 months, from a total of 65 clinicians. Most teleconsultations were with the family at home. Generally, video consultation was used for follow-up, after at least one face-to-face visit. A total of 132 users (specialist and regional clinicians, patients and families) responded to an online survey. The major reason for both clinicians and families participating in telehealth was the savings in families' travel time. Key factors for the successful implementation of telehealth at the RCH include: a clear organisational vision; simple web-based technology; clinician ownership; sustained support. The RCH experience suggests that telehealth is suitable for both simple and highly complex paediatric patients. PMID- 24218351 TI - Development and implementation of a web-based continuing professional development (CPD) programme on medical genetics. AB - We developed, implemented and evaluated a web-based continuing professional development (CPD) programme on medical genetics. Development of the CPD programme followed the ADDIE model, i.e. Analysis, Design, Develop, Implement and Evaluation. An invitation to participate in a needs analysis survey was sent to all doctors on the email list of the Sri Lanka Medical Association. A total of 129 completed surveys was received (57% of the 228 who accessed the online survey). The average age of respondents was 42 years (range 27-81). The male: female ratio was approximately 2 : 1. Almost all respondents (96%) selected web based CPD programmes, or web-based and conventional lectures, as their preferred method of learning. The programme was piloted on a group of 10 doctors. The average pre-knowledge score was 40.3 and the post-knowledge score was 62.1 marks out of 100 (P = 0.002). We conclude that a web-based CPD programme on medical genetics is feasible in Sri Lanka. PMID- 24218352 TI - A break-even analysis of delivering a memory clinic by videoconferencing. AB - We analysed the costs of two kinds of dementia clinic. In the conventional clinic, held in a rural area, the specialist travels to the clinic from the city. In the videoconferencing clinic, patients are also seen in a rural area, but the specialist conducts the assessment by video from the city. The fixed costs common to both modalities, such as clinic infrastructure, were ignored. The total fixed cost of a monthly conventional clinic was $522 and the total fixed cost of a monthly videoconferencing clinic was $881. The additional variable cost of the specialist travelling to the conventional clinic was $2.62 per minute of the specialist's travelling time. The break-even point at which the cost of the two modalities is the same was just over two hours (138 min round trip). A sensitivity analysis showed that the break-even point was not particularly sensitive to changes in staff wages, but slightly more sensitive to the non labour costs of videoconferencing. Air travel is not an efficient alternative to travel by car. Reducing the number of clinics to six per year results in a much higher cost of running the videoconferencing service compared to the conventional service. Videoconferencing for the purpose of diagnosing dementia is both a reliable and cost effective method of health service provision when a specialist is required to drive for more than about two hours (round trip) to provide a memory disorder clinic service. PMID- 24218353 TI - Changes in paediatric hospital ENT service utilisation following the implementation of a mobile, indigenous health screening service. AB - In 2009, we established a mobile ear-screening service for children in a remote community approximately 350 km north-west of Brisbane. We compared pre implementation health service utilisation data (2006-2008) with data for the following three years. The study included only children in schools that had participated in screening since the start of the screening programme and for which data for the 6-year study period were available. In the baseline period there were 329 ear, nose and throat (ENT) outpatient appointments at the Royal Children's Hospital (RCH) in Brisbane for children from the selected catchment area. Of these, 166 (51%) were failure-to-attends (FTAs). In the following three years, there were 105 appointments, of which 40 (38%) were FTAs. In the baseline period, 100 children received surgical procedures at the RCH; in the following three years there were 43. In the three years following implementation, 136 children were booked to receive surgical procedures locally at the Cherbourg hospital, and 117 (86%) were completed. Since no other major health service changes occurred in the region during the study period, we conclude that the telemedicine-enabled screening service improved access to specialist care in the community and resulted in fewer outpatient and surgical appointments at the tertiary centre in Brisbane. PMID- 24218354 TI - The relationship between telehealth and information technology ranges from that of uneasy bedfellows to creative partnerships. AB - The relationship between the clinical and technical aspects of a telehealth operation is frequently problematic, and technically-driven projects often fail to achieve sustainability. Qualitative data from a study of 37 Australian telehealth services were analysed to understand how the relationship between telehealth providers and information technology (IT) departments helps or hinders the development of telehealth. The most frequent difficulties reported were between telehealth services and the internal IT departments of health services, rather than with external vendors. The difficulties included barriers to installing telehealth over IT networks, a lack of priority given to telehealth services, and IT departments insisting on standardised approach. Alternatively, when IT staff were assigned to supporting clinical staff and had a close working relationship with them, they were major enablers of telehealth services. Authorising dedicated IT support and encouraging joint problem solving should provide a strong foundation for a healthy relationship which contributes to the growth and sustainability of telehealth. PMID- 24218355 TI - Teleconsultation from a secondary hospital for paediatric emergencies occurring at rural hospitals in Queensland. AB - We reviewed telehealth consultations for acute paediatric patients presenting at rural sites in the Mackay district in 2012. Patient data and outcomes were collected prospectively, and a survey of the referring clinicians was undertaken. Thirty four patient consultations were conducted via telehealth with 14 referring clinicians. Most of the referrals were for respiratory illnesses, including bronchiolitis. We received feedback surveys for 16 consultations (57% response rate). In 47% of the cases, the paediatric team felt that transfer was avoided by using teleconsultation. In 80% of consultations, the referring clinicians felt that video consultation was more effective than telephone alone. In 30% of cases, the referring clinicians felt that the patient would have been transferred to higher facility in the absence of the telehealth facility. Clinicians thought that almost all consultations had educational value and reduced their anxiety in dealing with acute paediatric problems. There were no adverse outcomes or delayed transfers of patients staying at their rural sites. We recommend that telehealth consultation occur for all enquiries about acute paediatric patients at rural sites, especially if transfer of the patient is being considered. PMID- 24218356 TI - Nucleating the development of telemedicine to support healthcare workers in resource-limited settings: a new approach. AB - Collegium Telemedicus (CT) offers a new approach to the problem of starting a store-and-forward telemedicine network for use in low resource settings. The CT organization provides a no-cost template to allow groups to start a network without delay, together with a peer-support environment for those operating the networks. A new group needs only to supply a Guarantor (who accepts responsibility for the work of the network) and a Coordinator (who operates the telemedicine network, allocating cases and ensuring that they are responded to). Communication takes place via secure messaging, which has several advantages over plain email, e.g. all the data are stored centrally, which means that they can be read from a hand-held device such as a smart phone, but do not need to be stored on that device. Users can access the system with a standard web browser. In the first three months, seven networks were established on the CT system by university groups in the US, the UK, Australia and New Zealand, and by a large, multinational humanitarian organisation. In the most active network, there were 86 telemedicine cases in the first three months, i.e. an average submission rate of 7 cases/week. The CT system appears to fulfil its aim of assisting doctors who wish to help colleagues in other countries by improving their access to specialist opinions, while allowing them to maintain control over the new network's use and development. The long term aim of the CT organization is to provide a means of improving the quality of health care at the point of delivery in low resource settings. PMID- 24218357 TI - Case study: the Interact Home Telehealth Project. AB - Two home telehealth technologies (the Intel Health Guide and the Apple iPad) were trialled by four clinical services of the Hunter New England Local Health District. The iPad was selected by the Paediatric Palliative Care Service, the Stroke Service and the Brain Injury Rehabilitation Service. The Intel Health Guide was selected by the Cardiac Coaching Service. The telehealth devices were loaned to a total of 102 patients for different lengths of time, depending on clinical needs, but typically for about 3 months. A total of 42 clinicians were involved. During the trial, 16 technical problems were recorded and resolved, most concerning problems with connectivity. Nonetheless, the use of home telehealth technologies was positively received by clinicians, management and patients alike. Telehealth is now being integrated into the standard practices of the health district. PMID- 24218358 TI - Long-term telerehabilitation of COPD patients in their homes: interim results from a pilot study in Northern Norway. AB - We investigated the feasibility of a long-term telerehabilitation service for COPD patients comprising exercise training at home, telemonitoring and education/self-management. The service was offered as a 2-year follow-up programme by a physiotherapist. Equipment included a treadmill, a pulse oximeter and a tablet computer. Participants had weekly videoconference sessions with the physiotherapist. A website was used to access a training programme and to fill in a daily diary and a training diary. Ten patients with moderate or severe COPD participated in a pilot study in Northern Norway. After more than one year, all participants were still participating actively and no drop-outs had occurred. On average, there were 2.0 training sessions/week, 3.3 measurements/week registered via the website and 0.5 videoconference contacts/week. There was a reduction of 27% in the COPD-related hospital costs. Feedback from the participants was very positive. Long-term telerehabilitation of COPD patients at home is feasible and interim results suggest that it reduces healthcare utilization. PMID- 24218359 TI - A pilot trial of emergency telemedicine in regional Western Australia. AB - An Emergency Telehealth Service (ETS) was established in August 2012 in Western Australia. High definition videoconferencing was used to deliver emergency telemedicine to rural emergency departments, mainly staffed by nurses. In the first 11 months, over 3000 episodes of care were provided. Telemedicine proved useful for many clinical problems and allowed clinicians to diagnose, treat and manage patients locally, reducing the need for transfer. In addition, ETS physicians assisted with clinical coordination and transfer of patients. Almost all teleconsultations (98%) were with nursing staff at sites without medical cover. Expansion of the ETS throughout Western Australia is currently being planned. PMID- 24218360 TI - Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L. AB - CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells. PMID- 24218362 TI - Synthesis and structure-activity relationship study of organometallic bioconjugates of the cyclic octapeptide octreotate. AB - The chemically stabilized somatostatin-derived cyclic octapeptide octreotate has a number of interesting applications in medicinal chemistry. Here, a number of different organometallic derivatives of octreotate were prepared, and their properties were investigated. Specifically, we report the synthesis and characterization of ruthenocene, ferrocene, and cobaltocenium octreotate derivatives and their fluorophore-labeled conjugates as well as a dicobalt hexacarbonyl alkyne functionalized octreotate. To provide further insights into their characteristics, the log P values and electrochemical properties of the novel metal conjugates were compared. For biological activity, we determined their toxicity in three different cell lines. Cellular uptake and colocalization of selected compounds were studied by fluorescence microscopy with particular focus on efficiency and specificity of their uptake through the somatostatin receptor SSTR to elucidate the value of the metallocene head group for its potential use as a nontoxic and universal peptide label. PMID- 24218363 TI - A new congenital disorder of glycosylation caused by a mutation in SSR4, the signal sequence receptor 4 protein of the TRAP complex. AB - Nearly 50 congenital disorders of glycosylation (CDG) are known, but many patients biochemically diagnosed with CDG do not have mutations in known genes. Here, we describe a 16-year-old male who was born with microcephaly, developed intellectual disability, gastroesophageal reflux and a seizure disorder. We identified a de novo variant in the X-linked SSR4 gene which encodes a protein of the heterotetrameric translocon-associated protein (TRAP) complex. The c.316delT causes a p.F106Sfs*53 in SSR4 and also reduces expression of other TRAP complex proteins. The glycosylation marker Glyc-ER-GFP was used to confirm the underglycosylation in fibroblasts from the patient. Overexpression of the wild type SSR4 allele partially restores glycosylation of the marker and of the other members of the TRAP complex. This is the first evidence that the TRAP complex, which binds to the oligosaccharyltransferase complex, is directly involved in N glycosylation. PMID- 24218361 TI - The immune system and head and neck squamous cell carcinoma: from carcinogenesis to new therapeutic opportunities. AB - Head and neck squamous cell carcinomas (HNSCCs) exhibit complex interactions with the host immune system that may simultaneously explain resistance to various therapeutic modalities and that may also provide opportunities for therapeutic intervention. Discoveries in immunologic research over the last decade have led to an increased understanding of these interactions as well as the development of a multitude of investigational immunotherapies. Here, we describe the interaction between HNSCC and the immune system, including a discussion of immune cells involved with tumor carcinogenesis and the role of immune-modulating factors derived from tumors. We also describe the current immunotherapeutic approaches being investigated for HNSCC, including a discussion of the successes and limitations. With this review, we hope to present HNSCC as a model to guide future research in cancer immunology. PMID- 24218365 TI - Correct developmental expression level of Rai1 in forebrain neurons is required for control of body weight, activity levels and learning and memory. AB - Potocki-Lupski syndrome (PTLS) is a genomic disorder associated with an ~3 Mb duplication in 17p11.2. Clinical features include leanness, intellectual disability, autistic features and developmental deficits. RAI1 gene dosage is associated with the PTLS phenotypes. To understand where and when Rai1 overexpression is detrimental, we generated a mouse that over-expresses Rai1 conditionally in forebrain neurons (I-Rai1). Phenotypic characterization of I Rai1 mice showed significant underweight, hyperactivity and impaired learning and memory ability compared with wild-type littermates. Doxycycline administration can turn off the transgene expression allowing the restoration of Rai1 normal expression levels. When the transgene was turned off from conception to 3 months of age, no phenotypic differences were observed between I-Rai1 and their wild type littermates. Surprisingly, we found that turning off the transgene expression before the onset of the phenotypes (1-3 months) or after the onset of the phenotypes (3-5 months) cannot prevent nor reverse the phenotypic outcomes. Our results indicate that Rai1 dosage in forebrain neurons is critical during the development and is related to body weight regulation, activity levels and learning and memory. PMID- 24218364 TI - DNAJC13 mutations in Parkinson disease. AB - A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case-control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch-German-Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology. PMID- 24218366 TI - SMN deficiency alters Nrxn2 expression and splicing in zebrafish and mouse models of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease affecting lower motor neurons. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, which result in reduced levels of functional SMN protein. Biochemical studies have linked the ubiquitously expressed SMN protein to the assembly of pre-mRNA processing U snRNPs, raising the possibility that aberrant splicing is a major defect in SMA. Accordingly, several transcripts affected upon SMN deficiency have been reported. A second function for SMN in axonal mRNA transport has also been proposed that may likewise contribute to the SMA phenotype. The underlying etiology of SMA, however, is still not fully understood. Here, we have used a combination of genomics and live Ca(2+) imaging to investigate the consequences of SMN deficiency in a zebrafish model of SMA. In a transcriptome analyses of SMN-deficient zebrafish, we identified neurexin2a (nrxn2a) as strongly down-regulated and displaying changes in alternative splicing patterns. Importantly, the knock-down of two distinct nrxn2a isoforms phenocopies SMN-deficient fish and results in a significant reduction of motor axon excitability. Interestingly, we observed altered expression and splicing of Nrxn2 also in motor neurons from the Smn(-/-);SMN2(+/+) mouse model of SMA, suggesting conservation of nrxn2 regulation by SMN in mammals. We propose that SMN deficiency affects splicing and abundance of nrxn2a. This may explain the pre synaptic defects at neuromuscular endplates in SMA pathophysiology. PMID- 24218367 TI - Comparative receptor tyrosine kinase profiling identifies a novel role for AXL in human stem cell pluripotency. AB - The extensive molecular characterization of human pluripotent stem cells (hPSCs), human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) is required before they can be applied in the future for personalized medicine and drug discovery. Despite the efforts that have been made with kinome analyses, we still lack in-depth insights into the molecular signatures of receptor tyrosine kinases (RTKs) that are related to pluripotency. Here, we present the first detailed and distinct repertoire of RTK characteristic for hPSC pluripotency by determining both the expression and phosphorylation profiles of RTKs in hESCs and hiPSCs using reverse transcriptase-polymerase chain reaction with degenerate primers that target conserved tyrosine kinase domains and phospho RTK array, respectively. Among the RTKs tested, the up-regulation of EPHA1, ERBB2, FGFR4 and VEGFR2 and the down-regulation of AXL, EPHA4, PDGFRB and TYRO3 in terms of both their expression and phosphorylation levels were predominantly related to the maintenance of hPSC pluripotency. Notably, the specific inhibition of AXL was significantly advantageous in maintaining undifferentiated hESCs and hiPSCs and for the overall efficiency and kinetics of hiPSC generation. Additionally, a global phosphoproteomic analysis showed that ~30% of the proteins (293 of 970 phosphoproteins) showed differential phosphorylation upon AXL inhibition in undifferentiated hPSCs, revealing the potential contribution of AXL mediated phosphorylation dynamics to pluripotency-related signaling networks. Our findings provide a novel molecular signature of AXL in pluripotency control that will complement existing pluripotency-kinome networks. PMID- 24218368 TI - Determination of outdoor tobacco smoke exposure by distance from a smoking source. AB - INTRODUCTION: An increasing number of cities and countries have implemented outdoor smoking restrictions at building entrances. The purpose of this study was to determine outdoor tobacco smoke (OTS) exposure as a function of distance from a smoking source. METHODS: Outdoor concentrations of ambient particulate matter smaller than 2.5 MUm in aerodynamic diameter (PM2.5) were measured at 4 different distances (1, 3, 6, and 9 m) from a simulated smoking source. Wind speed and direction were measured using a wind meter. In total, 98 experiments were conducted on an outdoor rooftop. The experiments were conducted in 5 days with average wind speed of 0.8+/-0.6 m/s. One smoking experiment consisted of 13min (5 nonsmoking min, 3 smoking min, and 5 more nonsmoking min). The difference between mean PM2.5 concentrations during smoking and nonsmoking conditions was determined as the OTS exposure. RESULTS: The OTS levels were 72.7, 11.3, 4.1, and 2.6 ug/m(3) at 1, 3, 6, and 9 m, respectively. Although the OTS levels decreased with increasing distance from the smoking source, the OTS levels were significantly higher than zero at all distances. The downwind OTS levels were significantly higher than upwind levels. The OTS levels were negatively associated with wind speed. CONCLUSIONS: The outdoor PM2.5 levels were significantly higher with smoking than without smoking. Because the OTS was detectable even at 9 m with only one cigarette smoking, the minimum distance from a smoking source to prevent OTS exposure should be at least 9 m. PMID- 24218369 TI - Hydridoborylene complexes and di-, tri-, and tetranuclear borido complexes with hydride ligands. AB - Mono- and dinuclear hydridoborylene complexes were prepared by intermetallic borylene transfer from Group VI borylene or metalloborylene reagents. The hydride and borylene ligands were found to interact with each other significantly, although the boron ligand retains much of its former borylene character. Zero valent platinum fragments were successively added to the dinuclear hydridoborylene complexes, resulting in tri- and tetranuclear borido complexes, in which the B-H interaction has been lost, and the hydride ligands now bridge two metal centers. The complexes were studied spectroscopically, crystallographically, and by DFT methods, and the unusual bonding situation in the M-B-H triangles of hydridoborylene complexes were evaluated. PMID- 24218370 TI - Plants: a source for new antimycobacterial drugs. AB - Tuberculosis, also called TB, is currently a major health hazard due to multidrug resistant forms of bacilli. Global efforts are underway to eradicate TB using new drugs with new modes of action, higher activity, and fewer side effects in combination with vaccines. For this reason, unexplored new sources and previously explored sources were examined and around 353 antimycobacterial compounds (Nat Prod Rep 2007; 24: 278-297) 7 have been previously reported. To develop drugs from these new sources, additional work is required for preclinical and clinical results. Since ancient times, different plant part extracts have been used as traditional medicines against diseases including tuberculosis. This knowledge may be useful in developing future powerful drugs. Plant natural products are again becoming important in this regard. In this review, we report 127 antimycobacterial compounds and their antimycobacterial activities. Of these, 27 compounds had a minimum inhibitory concentration of < 10 ug/mL. In some cases, the mechanism of activity has been determined. We hope that some of these compounds may eventually develop into effective new drugs against tuberculosis. PMID- 24218371 TI - Inhibition of G protein-activated inwardly rectifying K+ channels by extracts of Polygonum persicaria and isolation of new flavonoids from the chloroform extract of the herb. AB - The G protein-activated inwardly rectifying K+ channel-modulatory activities of Polygonum persicaria extracts were investigated by using an automated patch-clamp method, with the aim of identifying natural sources of promising ion channel blocking compounds. The chloroform extract of the whole plant at 0.1 mg/mL exhibited high G protein-activated inwardly rectifying K+ channel-inhibitory activity. Fractionation of this extract by vacuum liquid chromatography on RP silica gel resulted in 6 fractions, which were evaluated for G protein-activated inwardly rectifying K+ channel-modulatory activity. RP-HPLC of the most active fractions afforded the main compounds 1-4 in pure form and a mixture containing the minor constituents. The structures were identified by means of UV, HRMS, and advanced NMR methods as 3-O-senecioyl-isorhamnetin (1), 3-O-angeloyl-isorhamnetin (2), 5,3',4',5'-tetramethoxy-6,7-methylenedioxyflavone (3), and 3,5,3',4',5' pentamethoxy-6,7-methylenedioxyflavone (4). Compounds 1-4 are new natural products, though 4 was reported earlier as a synthetic compound. Neither the individual, nor the combined application of compounds 1-4 modified the G protein activated inwardly rectifying K+ channel activity. However, a marked G protein activated inwardly rectifying K+ current-inhibitory effect was detected on use of the HPLC eluates containing the minor compounds. These results indicate the presence of electrophysiologically active agents among the minor compounds. PMID- 24218372 TI - Inhibition of beta-catenin signaling involved in the biological activities of a lignan E2S isolated from Carya cathayensis fruits. AB - Carya cathayensis is a fruit-bearing plant that belongs to the Juglandaceae family and is widely distributed throughout the world. It possesses various important biological activities. We have previously isolated an antitumor compound from the shell of C. cathayensis fruits and named it E2S ((E)-3-[(2S,3R) 2,3-dihydro-2-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-1 benzo[b]furan-5-yl]-2-propenal). In this study, we investigated the antitumor activity of E2S against various human colorectal cancer cell lines (HCT116, HT29, SW480, LoVo). The results showed that E2S could significantly inhibit the growth of cancer cells in a dose-dependent manner, as well as disrupt the progression of the cell cycle. Mechanistic study revealed that E2S could decrease the protein levels of beta-catenin and its downstream targets (such as c-myc, a key transcriptional target of beta-catenin) in the cells. In addition, it also significantly suppressed beta-catenin/TCF transcriptional activity. Taken together, the results suggested that E2S might partially exert an antiproliferative effect on human colorectal cancer cells by targeting beta catenin signaling, a finding that might potentially translate into a chemotherapeutic strategy for the treatment of cancer. It might also have implications for cancer prevention strategies. PMID- 24218373 TI - Testing to prevent colon cancer: results from a rural community intervention. AB - PURPOSE: Colon cancer is the second leading cause of cancer death in the United States. Despite tests that can detect and enable removal of precancerous polyps, effectively preventing this disease, screening for colon cancer lags behind other cancer screening. The purpose of this study was to develop and test a community based participatory approach to increase colon cancer screening. METHODS: Using a community-based participatory research approach, the High Plains Research Network and their Community Advisory Council developed a multicomponent intervention Testing to Prevent Colon Cancer-to increase colon cancer screening. A controlled trial compared 9 intervention counties in northeast Colorado with 7 control counties in southeast Colorado. We performed a baseline and postintervention random digit-dial telephone survey and conducted both intent-to-treat and on treatment analyses. RESULTS: In all, 1,050 community members completed a preintervention questionnaire and 1,048 completed a postintervention questionnaire. During the study period, there was a 5% absolute increase in the proportion of respondents who reported ever having had any test in the intervention region (from 76% to 81%) compared with no increase in the control region (77% at both time points) (P = .22). No significant differences between these groups were found in terms of being up to date generally or on specific tests. The extent of exposure to intervention materials was associated with a significant and cumulative increase in screening. CONCLUSIONS: This community based multicomponent intervention engaged hundreds of community members in wide dissemination aimed at increasing colorectal cancer screening. Although we did not find any statistically significant differences, the findings are consistent with an intervention-related increase in screening and provide preliminary evidence on the effectiveness of such interventions to improve colon cancer screening. PMID- 24218374 TI - Effects of patient-centered medical home attributes on patients' perceptions of quality in federally supported health centers. AB - PURPOSE: We sought to assess patients' ratings of patient-centered medical home (PCMH) attributes and overall quality of care within federally supported health centers. METHODS: Data were collected through the 2009 Health Center Patient Survey (n = 4,562), which consisted of in-person interviews and included a nationally representative sample of patients seen in health centers. Quality measures included patients' perceptions of overall quality of services, perceptions of quality of clinician advice/treatment, and likelihood of referring friends and relatives to the health center. PCMH attributes included (1) access to care getting to health center, (2) access to care during visit, (3) patient centered communication with health care clinicians, (4) patient-centered communication with support staff, (5) self-management support for chronic conditions, (6) self-management support for behavioral risks, and (7) comprehensive preventive care. Bivariate analysis and logistic regressions were used to examine associations between patients' perceptions of PCMH attributes and patient-reported quality of care. RESULTS: Eighty-four percent of patients reported excellent/very good overall quality of services, 81% reported excellent/very good quality of clinician care, and 84% were very likely to refer friends and relatives. Higher patient ratings on the access to care and patient centered communication attributes were associated with higher odds of patient reported high quality of care on the 3 outcome measures. CONCLUSIONS: More than 80% of patients perceived high quality of care in health centers. PCMH attributes related to access to care and communication were associated with greater likelihood of patients reporting high-quality care. PMID- 24218375 TI - Patients' experiences in different models of community health centers in southern China. AB - PURPOSE: Current health care reforms in China have an overall goal of strengthening primary care through the establishment and expansion of primary care networks based on community health centers (CHCs). Implementation in urban areas has led to the emergence of different models of ownership and management. The objective of this study was to evaluate the primary care experiences of patients in the Pearl River Delta as measured by the Primary Care Assessment Tool (PCAT) and the relationships with ownership and management in the 3 different models we describe. METHODS: This cross-sectional study was conducted on-site at CHCs in 3 cities within the Pearl River Delta, China, using a multistage cluster sampling method. A validated Mandarin Chinese version of the PCAT-Adult Edition (short version) was adopted to collect information from adult patients regarding their experiences with primary care sources. PCAT scores for individual primary care attributes and total primary care assessment scores were assessed with respect to sociodemographic characteristics, health characteristics, and health care service utilization across 3 primary care models. RESULTS: One thousand four hundred forty (1,440) primary care patients responded to the survey, for an overall response rate of 86.1%. Respondents gave government-owned and -managed CHCs the highest overall PCAT scores when compared with CHCs either managed by hospitals (95.18 vs 90.81; P = .005) or owned by private and social entities (95.18 vs 90.69; P =.007) as a result of better first-contact care (better first contact utilization) and coordination of care (better service coordination and information system). Factors that were positively and significantly associated with higher overall assessment scores included the presence of a chronic condition (P <.001), having medical insurance (P = .006), and a self-reported good health status (P <.001). CONCLUSIONS: This study suggests that government owned and -managed CHCs may be able to provide better first-contact care in terms of utilization and coordination of care, and may be better at solving the problem of underutilization of the CHCs as the first-contact point of care, one key problem facing the reforms in China. PMID- 24218376 TI - The enduring impact of what clinicians say to people with low back pain. AB - PURPOSE: The purpose of this study was to explore the formation and impact of attitudes and beliefs among people experiencing acute and chronic low back pain. METHODS: Semistructured qualitative interviews were conducted with 12 participants with acute low back pain (less than 6 weeks' duration) and 11 participants with chronic low back pain (more than 3 months' duration) from 1 geographical region within New Zealand. Data were analyzed using an Interpretive Description framework. RESULTS: Participants' underlying beliefs about low back pain were influenced by a range of sources. Participants experiencing acute low back pain faced considerable uncertainty and consequently sought more information and understanding. Although participants searched the Internet and looked to family and friends, health care professionals had the strongest influence upon their attitudes and beliefs. Clinicians influenced their patients' understanding of the source and meaning of symptoms, as well as their prognostic expectations. Such information and advice could continue to influence the beliefs of patients for many years. Many messages from clinicians were interpreted as meaning the back needed to be protected. These messages could result in increased vigilance, worry, guilt when adherence was inadequate, or frustration when protection strategies failed. Clinicians could also provide reassurance, which increased confidence, and advice, which positively influenced the approach to movement and activity. CONCLUSIONS: Health care professionals have a considerable and enduring influence upon the attitudes and beliefs of people with low back pain. It is important that this opportunity is used to positively influence attitudes and beliefs. PMID- 24218377 TI - Multimorbidity in patients attending 2 Australian primary care practices. AB - PURPOSE: Multiple chronic conditions in a single patient can be a challenging health burden. We aimed to examine patterns and prevalence of multimorbidity among patients attending 2 large Australian primary care practices and to estimate disease severity burden using the Cumulative Illness Rating Scale (CIRS). METHODS: Using published CIRS guidelines and a disease severity index calculated for each individual, we extracted data from the medical records of all 7,247 patients (58.5% female) seen over 6 months in 2008 who were rated for chronic conditions across 14 anatomical domains. RESULTS: Fifty-two percent of patients had multimorbidity in 2 or more CIRS domains, ranging from 20.6% if younger than 25 years, 43.7% if aged 25 to 44 years, 75.5% if aged 45 to 64 years, 87.5% if aged 65 to 74 years, and 97.1% if aged 75 years and older. Using a cutoff of 3 or more CIRS domains, 34.5% had multimorbidity ranging from 4.8% if younger than 25 years, 22.3% if aged 25 to 44 years, 56.1% if aged 45 to 64 years, 74.6% if aged 65 to 74 years, and 92.0% if aged 75 years and older. Musculoskeletal, singularly or in combination with others, was the commonest morbidity domain. The moderate severity index category increased with increasing age. CONCLUSIONS: Multimorbidity is a significant problem in men and women across all age-groups, and the moderate severity index increases with age. The musculoskeletal domain was most commonly affected. Mild and moderate severity index categories may underrepresent disease burden. Severity burden assessment in the primary care setting needs to take into account the severity index, as well as levels of domain severity within the index categories. PMID- 24218378 TI - Relationship quality and patient-assessed quality of care in VA primary care clinics: development and validation of the work relationships scale. AB - PURPOSE: Efforts to better understand the impact of clinic member relationships on care quality in primary care clinics have been limited by the absence of a validated instrument to assess these relationships. The purpose of this study was to develop and validate a scale assessing relationships within primary care clinics. METHODS: The Work Relationships Scale (WRS) was developed and administered as part of a survey of learning and relationships among 17 Department of Veterans Affairs (VA) primary care clinics. A Rasch partial-credit model and principal components analysis were used to evaluate item performance, select the final items for inclusion, and establish unidimensionality for the WRS. The WRS was then validated against semistructured clinic member interviews and VA Survey of Healthcare Experiences of Patients (SHEP) data. RESULTS: Four hundred fifty-seven clinicians and staff completed the clinic survey, and 247 participated in semistructured interviews. WRS scores were significantly associated with clinic-level reporting for 2 SHEP variables: overall rating of personal doctor/nurse (r(2) =0.43, P <.01) and overall rating of health care (r(2)= 0.25, P <.05). Interview data describing relationship characteristics were consistent with variability in WRS scores across low-scoring and high-scoring clinics. CONCLUSIONS: The WRS shows promising validity as a measure assessing the quality of relationships in primary care settings; moreover, primary care clinics with lower WRS scores received poorer patient quality ratings for both individual clinicians and overall health care. Relationships play an important role in shaping care delivery and should be assessed as part of efforts to improve patient care within primary care settings. PMID- 24218379 TI - Cultivating a cycle of trust with diverse communities in practice-based research: a report from PRIME Net. AB - PURPOSE: Practice-based research networks (PBRNs) are increasingly seen as important vehicles to translate research into practice, although less is known about the process of engaging diverse communities in PBRN research. The objective of this study was to identify strategies for successfully recruiting and retaining diverse racial/ethnic communities into PBRN research studies. METHODS: This collaborative, multisite study engaged 5 of the 8 networks of the PRImary care MultiEthnic Network (PRIME Net) consortium that conducts research with traditionally underrepresented/underserved populations. We used a sequential, qualitative research design. We first conducted 1 key informant interview with each of 24 researchers experienced in recruiting research participants from 5 racial/ethnic communities (African American, Arab/Chaldean, Chinese, Hispanic, and Native American). Subsequently, we conducted 18 focus groups with 172 persons from these communities. RESULTS: Participants' comments indicated that successful recruitment and retention of underrepresented populations in PBRN studies is linked to the overall research process. This process, which we termed the cycle of trust, entailed developing and sustaining relationships of trust during 4 interrelated stages: before the study, during study recruitment, throughout study conduct, and after study completion. Participants identified a set of flexible strategies within each stage and called for close engagement with clinic and community partners. CONCLUSIONS: Our participants suggest that approaches to research that lay a foundation of trust, demonstrate respect for community members, and extend beyond the enrollment and data collection phases are essential to enhance the participation of diverse populations in PBRN research. These findings offer the PBRN community a guide toward achieving this important goal. PMID- 24218380 TI - Number needed to benefit from information (NNBI): proposal from a mixed methods research study with practicing family physicians. AB - PURPOSE: We wanted to describe family physicians' use of information from an electronic knowledge resource for answering clinical questions, and their perception of subsequent patient health outcomes; and to estimate the number needed to benefit from information (NNBI), defined as the number of patients for whom clinical information was retrieved for 1 to benefit. METHODS: We undertook a mixed methods research study, combining quantitative longitudinal and qualitative research studies. Participants were 41 family physicians from primary care clinics across Canada. Physicians were given access to 1 electronic knowledge resource on handheld computer in 2008-2009. For the outcome assessment, participants rated their searches using a validated method. Rated searches were examined during interviews guided by log reports that included ratings. Cases were defined as clearly described searches where clinical information was used for a specific patient. For each case, interviewees described information-related patient health outcomes. For the mixed methods data analysis, quantitative and qualitative data were merged into clinical vignettes (each vignette describing a case). We then estimated the NNBI. RESULTS: In 715 of 1,193 searches for information conducted during an average of 86 days, the search objective was directly linked to a patient. Of those searches, 188 were considered to be cases. In 53 cases, participants associated the use of information with at least 1 patient health benefit. This finding suggested an NNBI of 14 (715/53). CONCLUSION: The NNBI may be used in further experimental research to compare electronic knowledge resources. A low NNBI can encourage clinicians to search for information more frequently. If all searches had benefits, the NNBI would be 1. In addition to patient benefits, learning and knowledge reinforcement outcomes are frequently reported. PMID- 24218381 TI - Testing to prevent colon cancer: how rural community members took on a community based intervention. AB - Participatory research can elevate research relevance and effectiveness. The literature contains few first-hand descriptions of community members engaged in research. In 2003, the High Plains Research Network convened a Community Advisory Council (CAC) that quickly began providing input, feedback, innovation, and dissemination efforts. After receiving a participatory research grant from the Centers for Disease Control and Prevention aimed at increasing colorectal cancer screening, the CAC participated in an intensive training on colon cancer prevention and spent 6 months developing a locally relevant intervention-Testing to Prevent Colon Cancer. CAC members participated in all aspects of the research including intervention messaging, survey design, recruitment, implementation, analysis and interpretation of data, and dissemination of results including presentations at national venues and coauthoring manuscripts. Our experience attests to the power of participatory research in efforts to improve health outcomes. PMID- 24218383 TI - What do you expect from a doctor? Six habits for healthier patient encounters. AB - Expectations lie at the heart of America's health care crisis. Although doctors cannot control for the unrealistic demands of a consumer-centric society, we might ask what we would want in a physician. Someone who listens longer and lets us express ourselves in our own words? Someone who cares about the outcome-our personal outcome-and not just the "clinical course"? Most patients do not demand perfection. Not cure. Not even relief, no matter what the TV commercials promise or how badly they wish them to be true. What we all desire is a plan that connects us to another human being-our doctor-which is a kind of relief all its own. The author identifies 6 simple habits that will lead to healthier, happier encounters with patients and their illness. PMID- 24218382 TI - Rediscovering community--reflections after Hurricane Sandy. AB - Hoboken, New Jersey, is a town of 50,000 residents located across the Hudson River from New York City. Most of Hoboken's infrastructure was compromised during Hurricane Sandy as a result of flooding and power outages that rendered many businesses inoperable, including all of the pharmacies in town. Despite a focus on emergency preparedness since Hurricane Katrina and 9/11, there were no contingencies in place to facilitate and assess the medication needs of the community in the event of a natural disaster. This essay describes how the author rediscovered the meaning of community, and through working with colleagues in other health care disciplines and non-health care volunteers, provided care to patients in suboptimal circumstances. PMID- 24218384 TI - AAFP releases third list of tests, procedures patients, physicians should question. PMID- 24218385 TI - The ABFM begins to use differential item functioning. PMID- 24218386 TI - STFM funds development of a residency accreditation toolkit. PMID- 24218387 TI - Another century of "reform without change?". PMID- 24218388 TI - FM-RC requirements - less is more. PMID- 24218390 TI - AHRQ updates on primary care research: clinical-community relationships. PMID- 24218391 TI - In this issue: working in community and improving health care quality. PMID- 24218392 TI - Eccentric contractions of gastrocnemius muscle-induced nerve damage in rats. AB - INTRODUCTION: We examined the effects of gastrocnemius eccentric contractions (ECs) on the sciatic nerve in rats. METHODS: Rats were divided randomly into the following 3 groups: control, 180EC (ECs with 180 degrees /s angular velocity), and 30EC (ECs with 30 degrees /s angular velocity). Twenty ECs were induced by electrical stimulation of the gastrocnemius. On days 3, 7, and 10 after the ECs, nerve conduction velocity (NCV) was measured, and sciatic nerve branches were harvested for analysis. RESULTS: A significant decrease in NCV was observed between the control and day-7 180EC. Significant reduction in the levels of myelin sheath protein zero (p0) between day 7 and day 3 180EC and a significant increase of macrophage-related protein and tyrosine kinase receptor C were observed between day 7 180EC and day 7 30EC. CONCLUSIONS: ECs with fast angular velocities induce functional and structural damage in innervating nerve. PMID- 24218394 TI - Noninflammatory necrotizing vasculopathy in lupus nephritis: a single-center experience. AB - In this study, we assessed the clinicopathological features of lupus nephritis patients with renal noninflammatory necrotizing vasculopathy (NNV). A total of 142 renal biopsies with lupus nephritis were reviewed, including nine cases presented with NNV and 36 without renal vascular lesions. The comparisons of clinical, laboratory and pathological features, treatments, as well as renal outcome between the two groups were further performed. In comparison with the no renal vascular lesions group, patients with NNV changes had significantly higher proportions of noninfection leukocyturia (p = 0.013) and leukocytopenia (p = 0.042), significantly higher serum creatinine (p = 0.012), lower hemoglobin (p = 0.002) and serum C3 (p < 0.001) levels. Renal pathological activity indices and chronicity indices were significantly higher in the NNV group (p = 0.002 and p = 0.006, respectively) than those in the no vascular lesions group. Regarding renal prognosis, the presence of NNV was not a risk factor for renal outcome (p = 0.327). In conclusion, NNV was not infrequent in renal biopsies of lupus nephritis. It was commonly associated with active clinical status and proliferative glomerular lesions of lupus. PMID- 24218396 TI - The gating charge should not be estimated by fitting a two-state model to a Q-V curve. AB - The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in most cases, it underestimates the moving charge times the fraction of the field. PMID- 24218395 TI - Cross-sectional and longitudinal evaluation of bone mass and quality in children and young adults with juvenile onset systemic lupus erythematosus (JSLE): role of bone mass determinants analyzed by DXA, PQCT and QUS. AB - INTRODUCTION: There are few prospective data on bone mass and quality in patients with juvenile onset systemic lupus erythematosus (JSLE). There are also few studies analyzing bone mass and quality determinants by using at the same time dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS). OBJECTIVE: The objective of this paper is to evaluate cross-sectionally and longitudinally bone mass and quality determinants in adolescents and young adults with JSLE, and to identify the main predictors of reduced bone mineral density (BMD) and bone quality using these techniques. METHODS: Fifty-six patients with JSLE (mean age 18.5 +/- 5.7 years) entered the study. In all subjects DXA scan at the lumbar spine, radius pQCT and phalangeal QUS were performed the same day. Of these, 46 patients (mean age 23.1 +/- 6.2 years) were revaluated with a second DXA, pQCT and QUS. The data obtained were compared with 72 and 80 age- and sex- matched healthy controls. RESULTS: At the first evaluation, JSLE patients had a reduced spine BMAD SDS (p < 0.001), and significantly lower levels of TrabBMD (p < 0.0001), SSIp (p < 0.05), AD-SoS and QUS z-score (p < 0.005) but not reduced muscle CSA and CBA values. CortBMD and FatCSA were significantly increased (p < 0.0001). These data were confirmed at longitudinal evaluation regarding spine BMAD SDS (p < 0.001), TrabBMD (p < 0.0001), FatCSA (p < 0.005), AD-SoS (p < 0.001), and QUS z-score (p < 0.005) but not muscle CSA (p <= 0.05) and CBA (p < 0.0001). SSIp and CortBMD longitudinal evaluation showed that JSLE patients did not present significant differences in comparison to controls. CONCLUSIONS: Patients with JSLE have a low bone mass without catch-up growth over time, causing a reduction of peak bone mass with high risk of osteoporosis in early adulthood. To reduce the risk, close monitoring of BMD, better control of disease activity, physical activity and dietary intake of calcium and vitamin D are advocated to ameliorate the loss of bone mass. In patients with proved osteoporosis therapeutic approaches including bisphosphonates should be considered. PMID- 24218397 TI - Molecular interactions involved in proton-dependent gating in KcsA potassium channels. AB - The bacterial potassium channel KcsA is gated open by the binding of protons to amino acids on the intracellular side of the channel. We have identified, via channel mutagenesis and x-ray crystallography, two pH-sensing amino acids and a set of nearby residues involved in molecular interactions that influence gating. We found that the minimal mutation of one histidine (H25) and one glutamate (E118) near the cytoplasmic gate completely abolished pH-dependent gating. Mutation of nearby residues either alone or in pairs altered the channel's response to pH. In addition, mutations of certain pairs of residues dramatically increased the energy barriers between the closed and open states. We proposed a Monod-Wyman-Changeux model for proton binding and pH-dependent gating in KcsA, where H25 is a "strong" sensor displaying a large shift in pKa between closed and open states, and E118 is a "weak" pH sensor. Modifying model parameters that are involved in either the intrinsic gating equilibrium or the pKa values of the pH sensing residues was sufficient to capture the effects of all mutations. PMID- 24218398 TI - Peregrination of the selectivity filter delineates the pore of the human voltage gated proton channel hHV1. AB - Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hHV1), because the proton concentration is >10(6) times lower than that of other cations. Here we use "selectivity filter scanning" to elucidate the molecular requirements for proton specific conduction in hHV1. Asp(112), in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels. After neutralizing Asp(112) by mutating it to Ala (D112A), we introduced Asp at each position along S1 from 108 to 118, searching for "second site suppressor" activity. Surprisingly, most mutants lacked even the anion conduction exhibited by D112A. Proton-specific conduction was restored only with Asp or Glu at position 116. The D112V/V116D channel strikingly resembled WT in selectivity, kinetics, and DeltapH-dependent gating. The S4 segment of this mutant has similar accessibility to WT in open channels, because R211H/D112V/V116D was inhibited by internally applied Zn(2+). Asp at position 109 allowed anion permeation in combination with D112A but did not rescue function in the nonconducting D112V mutant, indicating that selectivity is established externally to the constriction at F150. The three positions that permitted conduction all line the pore in our homology model, clearly delineating the conduction pathway. Evidently, a carboxyl group must face the pore directly to enable conduction. Molecular dynamics simulations indicate reorganization of hydrogen bond networks in the external vestibule in D112V/V116D. At both positions where it produces proton selectivity, Asp frequently engages in salt linkage with one or more Arg residues from S4. Surprisingly, mean hydration profiles were similar in proton-selective, anion permeable, and nonconducting constructs. That the selectivity filter functions in a new location helps to define local environmental features required to produce proton-selective conduction. PMID- 24218399 TI - Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally. AB - OBJECTIVES: Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia. CdLS has also been associated with decreased PAPP-A and increased nuchal translucency (NT). We reviewed NIPBL sequence analysis results for 12 prenatal samples in our laboratory to determine the frequency of mutations in our cohort. METHODS: This retrospective study analyzed data from all 12 prenatal cases with suspected CdLS, which were received by The University of Chicago Genetic Services Laboratories. Diagnostic NIPBL sequencing was performed for all samples. Clinical information was collected from referring physicians. RESULTS: NIPBL mutations were identified in 9 out of the 12 cases prenatally (75%). Amongst the NIPBL mutation-positive cases with clinical information available, the most common findings were upper limb malformations and micrognathia. Five patients had NT measurements in the first trimester, of which four were noted to be increased. CONCLUSION: We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations. PMID- 24218400 TI - Plasma levels of stromal cell-derived factor-1 (CXCL12) and circulating endothelial progenitor cells in women with idiopathic heavy menstrual bleeding. AB - STUDY QUESTION: Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors? SUMMARY ANSWER: Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs. WHAT IS KNOWN ALREADY: Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs. STUDY DESIGN, SIZE, DURATION: A prospective cohort study in a university hospital setting. Between 2008 and 2009 10 HMB-E patients were recruited from Karolinska University Hospital. Ten healthy women were also included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ten healthy control women and 10 HMB-E patients, all with regular menstrual cycles, provided 4 blood samples during a single menstrual cycle: 2 in the proliferative phase, 1 at ovulation and 1 in the secretory phase. We assessed plasma levels of CXCL12, vascular endothelial growth factor A(165) (VEGFA), basic fibroblast growth factor (bFGF) and granulocyte and granulocyte-macrophage colony stimulating factors by ELISA. We counted circulating EPC-CFUs by culture, and ECs and EPCs by flow cytometry and immunostaining for cell surface markers. MAIN RESULTS AND THE ROLE OF CHANCE: Plasma levels of CXCL12 were significantly lower in HMB-E patients compared with control women (P < 0.0001), with a significant decrease (P = 0.013) between the proliferative phase and ovulation. VEGFA showed a trend towards the same decreasing pattern as CXCL12, although not statistically significant (P = 0.086), whereas systemic VEGFA levels in control women remained unchanged across the different phases of the menstrual cycle (P = 0.473). HMB-E patients had a lower number of EPC-CFUs compared with control women (P = 0.014), with a positive correlation between the level of CXCL12 and EPC-CFUs (r = 0.428; P = 0.047). Whilst the level of circulating endothelial cells in HMB-E patients was higher than in control women, this did not reach statistical significance. In contrast, the levels of the hematopoietic/EPC marker CD34 were significantly lower in HMB-E patients than control women (P < 0.020). LIMITATIONS, REASONS FOR CAUTION: Small sample, unknown source of CXCL12, unknown balance between influx and efflux of EPCs from bone marrow and to the endometrium. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that CXCL12 may play an important role in physiological angiogenesis in the endometrium, and that low and dysregulated levels of CXCL12 in women with HMB-E could affect vessel quality, integrity and repair. STUDY FUNDING/COMPETING INTEREST(S): Financial support was provided through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet (number 20110258). This study was also supported by grants from the Swedish Labor Market Insurance. The authors have no conflict of interest to declare. PMID- 24218401 TI - Dyadic dynamics of perceived social support in couples facing infertility. AB - STUDY QUESTION: Is perceived social support from partner, family, and friends associated with increased infertility-related stress? SUMMARY ANSWER: While men's perceived support did not seem to influence their partners' stress, women's perceptions of spousal and familial support can affect the way men deal with the challenge of infertility. WHAT IS KNOWN ALREADY: Previous studies showed that low levels of social support are associated with poor psychosocial adjustment and treatment termination in women and men. Studies examining the impact of social support using the couple as unit of analysis are lacking. STUDY DESIGN, SIZE, DURATION: A cross-sectional sample of 613 Portuguese patients participated in the research, online over a 3-month period, and in a public fertility clinic over 11 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: The final sample comprised 213 married or cohabiting couples (191 from the fertility clinic) who were actively attempting to have a child, were seeking infertility treatment and had not undergone previous preimplantation genetic diagnosis. Perceived social support was assessed through the Multidimensional Scale of Perceived Social Support and infertility-related stress was assessed with the fertility problem inventory. Hypotheses were tested by applying the actor-partner interdependence model using structural equation modeling. MAIN RESULTS AND THE ROLE OF CHANCE: Couples had been living together for an average (+/-SD) of 6 +/- 3.5 years, and attempting a pregnancy for 3.8 +/- 2.6 years. Nearly half of the couples had undergone infertility treatment (41.3%). Infertility stress was found to be associated with low family support for women (beta = -0.27, P = .003), and low partner support for both men (beta = -0.29, P = .001) and women (beta = -0.45, P = .006). Both women and men's perceived friend support were not significantly related to male or female infertility stress. Men infertility stress was also associated with their partners low levels of partner (beta = -0.24, P = .049) and family support (beta = -0.23, P < .001). No significant partner effects were observed for women. Despite being related to actor effects alone (female partner and family support), the explained variance of the model in women's fertility stress was greater (R(2) = 21%) than that (R(2) = 15.6%) for the combined actor and partner effects in men's fertility stress (male partner support, female partner and family support). LIMITATIONS, REASONS FOR CAUTION: The study data are cross-sectional and the generalizability of results is limited by self-selection. The characteristics of non-participants in both the clinical and online samples were not available, the perception of infertility-specific supportive behaviors was not assessed and differential analyses according to infertility diagnosis were not included in this study. WIDER IMPLICATIONS OF THE FINDINGS: Our data underline the importance of partner support in alleviating the burden of infertility. Men may experience infertility indirectly through the impact that it has on their partners. Our findings reinforce the need to involve the male partner throughout the whole treatment process and for couple-based interventions when providing infertility counseling. Further prospective research should be aimed at investigating the male experience of infertility. STUDY FUNDING/COMPETING INTEREST: This research was supported by a PhD scholarship from the Portuguese Foundation for Science and Technology granted to M.M. (FCT, SFRH/BD/44232/2008). The authors have no conflicts of interest to declare. PMID- 24218402 TI - Microsurgical vasoepididymostomy is an effective treatment for azoospermic patients with epididymal obstruction and prior failure to achieve pregnancy by sperm retrieval with intracytoplasmic sperm injection. AB - STUDY QUESTION: Can microsurgical vasoepididymostomy (MVE) be used to treat azoospermia in men with epididymal obstruction who have had a prior attempt at sperm retrieval with ICSI and failed to achieve a pregnancy? SUMMARY ANSWER: MVE is an effective treatment for epididymal obstruction. WHAT IS KNOWN ALREADY: MVE is an effective treatment for non-vasectomized patients with epididymal obstruction. However, ICSI is the preferred treatment for patients with obstructive azoospermia in some reproductive centers. The clinical pregnancy rate in per ICSI cycle is <40% and more than half of couples need repeated ICSI. Some couples cannot bear the high medical costs or the pain associated with repeated IVF/ICSI. Therefore, MVE may be an alternative treatment for such patients. STUDY DESIGN, SIZE AND DURATION: This retrospective study investigated whether MVE could be used to treat patients with epididymal obstruction and a previous failed ICSI attempt. From January 2009 to July 2012, 268 patients underwent MVE for epididymal obstruction in our center; we included 68 who had experienced failure of at least one cycle of ICSI in this study. MATERIALS, SETTING, METHODS: We studied 68 patients with obstructive azoospermia who were treated by MVE and had previously undergone surgical sperm recovery and ICSI. The patients were divided into two groups according to the sperm retrieval method used in their ICSI attempt: percutaneous epididymal sperm aspiration (PESA) (41.2%, 28/68) and testicular sperm extraction (TESE) (58.8%, 40/68). We evaluated the obstructive causes, patency, pregnancy and live birth rates and the effect of sperm retrieval methods on the outcome of MVE. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 62 patients (91.2%) showed epididymal obstruction, 2 (2.9%) intratesticular obstruction and 4 (5.9%) vasal obstruction. The mean age was 30.4 +/- 5.3 years (range 22-48 years). We followed up 53 (85.5%) at a mean follow-up of 19.8 +/- 9.1 months (range 6-43 months). The total patency and natural pregnancy rates were 79.2% (n = 42) and 35.8% (n = 19), respectively. The overall live birth rate was 28.3%. The results of MVE did not differ between the two groups: PESA and TESE. LIMITATIONS, REASONS FOR CAUTION: A randomized controlled trial comparing pregnancy rates, live birth rates, risks and medical costs of MVE and IVF/ICSI is needed. The size of our sample was limited, so we did not reveal significantly different patency, pregnancy and live birth rates between PESA and TESE. A larger sample size is needed to evaluate the effect of sperm retrieval on patency, pregnancy and live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: Epididymal obstruction is the most common obstructive cause in non-vasectomized patients. Data from this study have shown that MVE is an effective therapy for such azoospermic patients with epididymal obstruction and prior failed ICSI for pregnancy. Obstructive causes should be differentiated to select optimal therapy for patients with obstructive azoospermia in reproductive centers. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no competing interests to declare. PMID- 24218403 TI - Oocyte cryopreservation and in vitro culture affect calcium signalling during human fertilization. AB - STUDY QUESTION: What are the precise patterns of calcium oscillations during the fertilization of human oocytes matured either in vivo or in vitro or aged in vitro and what is the effect of cryopreservation? SUMMARY ANSWER: Human oocytes matured in vivo exhibit a specific pattern of calcium oscillations, which is affected by in vitro maturation, in vitro ageing and cryopreservation. WHAT IS KNOWN ALREADY: Oscillations in cytoplasmic calcium concentration are crucial for oocyte activation and further embryonic development. While several studies have described in detail the calcium oscillation pattern during fertilization in animal models, studies with human oocytes are scarce. STUDY DESIGN, SIZE, DURATION: This was a laboratory-based study using human MII oocytes matured in vivo or in vitro either fresh or after cryopreservation with slow freezing or vitrification. Altogether, 205 human oocytes were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: In vivo and in vitro matured human oocytes were used for this research either fresh or following vitrification/warming (V/W) and slow freezing/thawing (F/T). Human oocytes were obtained following written informed consent from patients undergoing ovarian hyperstimulation. For the calcium pattern analysis, oocytes were loaded with the ratiometric calcium indicator fluorescent dye Fura-2. Following ICSI using sperm from a single donor, intracellular calcium was measured for 16 h at 37 degrees C under 6% CO(2). The calcium oscillation parameters were calculated for all intact oocytes that showed calcium oscillations and were analyzed using the Mann-Whitney U-test. MAIN RESULTS AND THE ROLE OF CHANCE: Human in vivo MII oocytes display a specific pattern of calcium oscillations following ICSI. This pattern is significantly affected by in vitro ageing, with the calcium oscillations occurring over a longer period of time and with a lower frequency, shorter duration and higher amplitude (P < 0.05). In vitro matured oocytes from the GV and MI stage exhibit a different pattern of calcium oscillations with calcium transients being of lower frequency and shorter duration compared with in vivo matured MII. In MI oocytes that reached the MII stage within 3 h the calcium oscillations additionally appear over a longer period of time (P < 0.05). In vivo MII oocytes show a different calcium oscillation pattern following V/W with calcium oscillations occurring over a longer period of time, with a higher amplitude and a lower frequency (P < 0.05). In vitro matured oocytes, either from the GV or the MI stage, also display an altered pattern of calcium oscillations after V/W and the parameters that were similarly affected in all these oocyte groups are the frequency and the amplitude of the calcium transients. Slow freezing/thawing differentially affects the calcium oscillation pattern of in vitro matured and in vitro aged oocytes. LIMITATIONS, REASONS FOR CAUTION: The relationship between a specific pattern of calcium oscillations and subsequent human embryonic development could not be evaluated since the calcium indicator used and the high-intensity excitation light impair development. Furthermore, all oocytes were derived from stimulated cycles and immature oocytes were denuded prior to in vitro maturation. WIDER IMPLICATIONS OF THE FINDINGS: Our data show for the first time how calcium signalling during human fertilization is affected by oocyte in vitro maturation, in vitro ageing as well as V/W and slow freezing/thawing. The analysis of calcium oscillations could be used as an oocyte quality indicator to evaluate in vitro culture and cryopreservation techniques of human oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a clinical research mandate from the Flemish Foundation of Scientific Research (FWO Vlaanderen, FWO09/ASP/063) to F.V.M, a fundamental clinical research mandate from the FWO-Vlaanderen (FWO05/FKM/001) to P.D.S and a Ghent University grant (KAN-BOF E/01321/01) to B.H. The authors have no conflict of interest to declare. PMID- 24218404 TI - Response to: 'Impact of gender on outcomes in ankylosing spondylitis' by Feldtkeller et al. PMID- 24218405 TI - Visualisation of structural damage as a surrogate marker of radiographic progression in patients with rheumatoid arthritis. PMID- 24218406 TI - Clinical epidemiology, diagnosis and treatment of visceral leishmaniasis in the Pokot endemic area of Uganda and Kenya. AB - Between 2000 and 2010, Medecins Sans Frontieres diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa. PMID- 24218407 TI - Evaluation of the diagnostic accuracy of a typhoid IgM flow assay for the diagnosis of typhoid fever in Cambodian children using a Bayesian latent class model assuming an imperfect gold standard. AB - Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (>= 38 degrees C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41-76), and specificity was 97.8% (95% confidence interval = 96-99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54-99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26-55), with a specificity of 98.2% (95% credible interval = 97-99). The model estimate sensitivity for IgMFA (>= 2+) was 77.9% (95% credible interval = 58-90), with a specificity of 97.5% (95% credible interval = 95-100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis. PMID- 24218408 TI - A longitudinal analysis of the effect of mass drug administration on acute inflammatory episodes and disease progression in lymphedema patients in Leogane, Haiti. AB - We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis endemic area of Haiti during 1995-2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P <= 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P <= 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes. PMID- 24218409 TI - Hospitalizations and costs incurred at the facility level after scale-up of malaria control: pre-post comparisons from two hospitals in Zambia. AB - There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with < 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions. PMID- 24218410 TI - Disease severity and mortality caused by dengue in a Dominican pediatric population. AB - Millions are infected with dengue yearly. We evaluated the epidemiological and clinical characteristics of pediatric patients infected with dengue in the Dominican Republic. The applicability of World Health Organization (WHO) warning signs for predicting severe dengue and mortality was also studied. This study was a cross-sectional retrospective review of patients with a clinical diagnosis of dengue. Univariate and multivariate analyses were performed to evaluate characteristics associated with severity and mortality. The study included 796 subjects: 288 subjects were classified as dengue, 290 subjects had alarm signs, and 207 subjects were classified as severe dengue. Common findings included thrombocytopenia (96%), abdominal pain (71%), and vomiting (59%). The most important factors associated with severe dengue were rash (P < 0.01), severe thrombocytopenia (P < 0.01), and anemia (P < 0.01). These signs and symptoms were also associated with mortality. This study validates the current WHO warning signs of severity. Rash and severe thrombocytopenia may be early warning signs and need additional study. PMID- 24218411 TI - Assessing the microbial quality of improved drinking water sources: results from the Dominican Republic. AB - Millennium Development Goal Target 7c (to halve between 1990 and 2015 the proportion of the global population without sustainable access to safe drinking water), was celebrated as achieved in 2012. However, new studies show that we may be prematurely celebrating. Access to safe drinking water may be overestimated if microbial water quality is considered. The objective of this study was to examine the relationship between microbial drinking water quality and drinking water source in the Puerto Plata region of the Dominican Republic. This study analyzed microbial drinking water quality data from 409 households in 33 communities. Results showed that 47% of improved drinking water sources were of high to very high risk water quality, and therefore unsafe for drinking. This study provides evidence that the current estimate of safe water access may be overly optimistic, and microbial water quality data are needed to reliably assess the safety of drinking water. PMID- 24218412 TI - Lack of evidence of increased West Nile virus disease severity in the United States in 2012. AB - Abstract. In the United States, West Nile virus (WNV) causes annual seasonal outbreaks that fluctuate in size and scope. There was a large multistate outbreak of WNV in 2012, with more human disease cases reported nationally than any year since 2003. We evaluated national surveillance data to determine if the higher number of WNV cases reported in 2012 was associated with changes in the epidemiology or severity of disease compared with 2004-2011. Despite an increased incidence of neuroinvasive disease in 2012, national surveillance data showed no evidence of changes in epidemiology or increased disease severity compared with the previous 8 years. PMID- 24218413 TI - Community perception, misconception, and discord regarding prevention and treatment of infection with human immunodeficiency virus in Addis Ababa, Ethiopia. AB - Approximately one million persons infected with human immunodeficiency virus (HIV) live in Ethiopia. Socio-cultural factors influence prevention and treatment adherence. We applied a qualitative descriptive approach to evaluate community perception, knowledge, and the role of spiritual factors in regard to HIV. We conducted 14 focus groups with sampling of HIV+ and HIV- participants (n = 52) by using open-ended questions. We coded and analyzed data for major themes. There are misconceptions, including transmission via casual contact, and pervasive beliefs of holy water as a cure. Many HIV-participants believe treatment is ineffective or incompatible with holy water. Most HIV+ participants believe treatment and holy water can be taken together, but experienced either pressure to stop treatment or stigma when taking medications. Participants emphasized the role of spiritual leaders in directing and shaping community perspectives on HIV. Ongoing community education via local initiatives, nation-wide structural and environmental strategies, and efforts tailored toward Ethiopian society to reconcile treatment with faith are crucial. PMID- 24218414 TI - National profile and treatment outcomes of adult smear-negative pulmonary TB patients in Benin. AB - BACKGROUND: In Benin, patients with smear-negative pulmonary TB (SNPTB) are of low priority in the National Tuberculosis Programme (NTP) and little is known about their profile or treatment outcomes. METHODS: A retrospective cohort study was carried out to determine characteristics and treatment outcomes in all adults registered with SNPTB in 2009. Findings were compared with patients with new smear-positive pulmonary tuberculosis (PTB) diagnosed in the same period. RESULTS: Of 3140 patients with PTB, 273 (8.7%) had SNPTB, with higher rates in northern and southwestern regions. SNPTB was associated with female gender, older age and HIV-positive status (p<0.01). Patients with SNPTB had a higher proportion of unsuccessful treatment outcomes compared with smear-positive PTB owing to death and loss to follow-up (LFU) (p<0.01). The region with the capital city had the highest rate of LFU. Differences in unsuccessful outcomes between SNPTB and smear-positive PTB were more apparent in persons who were HIV-negative, and among HIV-positives not on antiretroviral treatment. CONCLUSION: In Benin, treatment outcomes of SNPTB patients were inferior to those with smear-positive PTB, with LFU being a major problem. The Benin NTP needs to better address the problem of patients with SNPTB in terms of monitoring and reporting, treatment management including that associated with HIV care, and reducing LFU. PMID- 24218416 TI - Propofol with ketamine following sedation with xylazine for routine induction of general anaesthesia in horses. AB - To document the suitability of intravenous propofol and ketamine following sedation with xylazine for routine anaesthetic induction in horses. Retrospective. 100 client-owned horses. Anaesthetic records were evaluated to determine: signalment, anaesthetic drug and dosages, need for additional induction agents, notation of any adverse events, duration of anaesthesia and recovery characteristics (rough or smooth, and rapid or prolonged). Horses were sedated with xylazine 0.99+/-(0.2) mg/kg intravenous and 23 horses were also administered butorphanol 0.02+/-(0.001) mg/kg intravenous. Horses were anaesthetised with a combination of propofol 0.40+/-(0.1) mg/kg intravenous and ketamine 2.8+/-(0.3) mg/kg intravenous. Six horses required additional ketamine. None became apnoeic and no adverse events were noted. Anaesthesia was maintained with isoflurane in 66 horses and a combination of guaifenesin, ketamine and xylazine (GKX) in 34 horses. Total anaesthesia time was 125.4+/-(46) minutes. Fifty-one horses were administered romifidine 0.016 (+/-0.008) mg/kg intravenous at recovery. Time from orotracheal extubation to standing was 27.6+/-(25) minutes. Of the 58 records with recovery characteristics, the number per category was: rapid n=6, prolonged n=3, smooth n=46, rough n=6. Intravenous propofol and ketamine following xylazine provided satisfactory anaesthetic inductions and recoveries in a varied population of horses without any clinically relevant adverse events. PMID- 24218415 TI - Risk factors for anemia in children under 6 years of age in Ethiopia: analysis of the data from the cross-sectional Malaria IndicatorSurvey, 2007. AB - BACKGROUND: Malaria is a leading cause of morbidity in Ethiopia. However, its transmission varies in both space and time, and large areas of the country are hypoendemic and epidemic-prone. The Ethiopia National Malaria Indicator Survey 2007 is a cross-sectional, nationally-representative household survey. The objective of the analyses presented here were to use the survey's data to identify factors associated with anemia presence in children under 6 years of age (U6); specifically, investigate the association between malaria and anemia; and discuss using anemia as a malaria proxy biomarker in the Ethiopian hypo-endemic transmission setting. METHODS: The survey sampled 4185 households in 347 enumeration areas <=2500 m above sea level. Primary outcome was increasing anemia severity in sampled children: no anemia (Hb: >=11g/dl); mild anemia (Hb: >=8g/dl and <11g/dl); and moderate-severe anemia (Hb: <8g/dl). Secondary outcomes were positive malaria rapid diagnostic test (RDT) or blood slide microscopy. RESULTS: The analysis included 6054 (92.0%) children U6 in 3962 households. The proportion of children with no anemia, mild anemia, and moderate-severe anemia was 63.6%, 31.3%, and 5.1%, respectively. The overall prevalence of anemia (Hb <11g/dl) was 36.4% (95% CI 34.4-38.4). Factors independently associated with reduced relative odds of anemia categories were age (OR=0.7, 95% CI 0.7-0.7) and female sex (OR=0.9, 95% CI 0.8-1.0); malaria RDT positivity was associated with increased relative odds of a more severe anemia category (OR=5.8, 95% CI 3.7-9.2). CONCLUSIONS: We conclude that at altitudes <=2500 m malaria appears to be a significant risk factor for anemia; potentially anemia could be used as a useful proxy biomarker for malaria and its control in Ethiopia. PMID- 24218417 TI - Predicting mortality in the critically ill: a tricky enterprise. PMID- 24218418 TI - Current concepts in the management of diabetic nephropathy. AB - Although much progress has been made in slowing the progression of diabetic nephropathy, renal dysfunction and development of end-stage renal disease (ESRD) remain major concerns in diabetes. In addition, diabetic patients with microalbuminuria have an increased cardiovascular mortality. Therefore, new treatment modalities or strategies are needed to prevent or slow the progression of diabetic nephropathy and prevent cardiovascular disease in diabetes. In this review we describe current concepts in pathophysiology, treatment goals and we discuss future developments in the treatment of diabetic nephropathy. Common risk factors for diabetic nephropathy and its progression are longer duration, poor glycaemic control, hypertension and the presence of albuminuria. Available treatment options, especially renin-angiotensin aldosterone system (RAAS) blockade, but also better blood pressure and blood glucose control, decrease the incidence of cardiovascular disease and renal disease in diabetes. It is important that treatment goals are tailored to the individual patient with individual treatment goals of glycaemic control and blood pressure, depending on age, type of diabetes and diabetes duration. Aggressive treatment of glucose control and blood pressure might not always be best practice for every patient. Since the proportion of ESRD due to diabetic nephropathy remains high, optimisation of RAAS blockade is advocated and can be achieved by adequate sodium restriction and/or diuretic treatment. Moreover, aldosterone blockade might be a valuable strategy, which has potency to slow the progression of diabetic renal disease. Other possible future interventions are under investigation, but large clinical trials have to be awaited to confirm the safety and efficacy of these drugs. PMID- 24218419 TI - Intestinal cholesterol secretion: future clinical implications. AB - Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues in the body to the faeces. In humans, faecal cholesterol elimination via the RCT pathway is considered to be restricted to excretion via the hepatobiliary route. Recently, however, direct trans-intestinal excretion of plasma-derived cholesterol (TICE) was shown to contribute substantially to faecal neutral sterol (FNS) excretion in mice. TICE was found to be amenable to stimulation by various pharmacological and dietary interventions in mice, offering new options to target the intestine as an inducible, cholesterol-excretory organ. The relevance of TICE for cholesterol elimination in humans remains to be established. There is, however, emerging evidence for the presence of TICE in human (patho) physiology. This review discusses our current understanding of TICE and its novel therapeutic potential for individuals at increased risk of cardiovascular disease. PMID- 24218420 TI - Monitoring of unfractionated heparin in critically ill patients. AB - BACKGROUND: In critically ill patients, dosing of unfractionated heparin (UFH) is difficult due to unpredictable pharmacokinetics, which has an impact on the time to reach therapeutic anticoagulation. We evaluated the quality of UFH therapy in critically ill patients in terms of activated partial thromboplastin time (APTT) test values and time to therapeutic range. METHODS: Patients admitted to the Intensive Care Unit (ICU) and Medium Care Unit (MCU) were screened for intravenous UFH administration. Time to therapeutic range was categorised into 0 12, 13-24 and >24 hours. APTT results were classified into categories of subtherapeutic, supratherapeutic and therapeutic tests. We identified to what extent the sub- and upratherapeutic values were aberrant of the limit of the therapeutic range (15%). RESULTS: In 101 patients admitted to the ICU and MCU, time to therapeutic range was 24 hours in 56% of the population, whereas in 10% of the patients no therapeutic APTT was achieved during UFH treatment. Among the APTT levels, 29% of all test results measured in 24 hours were within the therapeutic range. Subtherapeutic values were found in 53% of the test results, of which 160/203 were more than 15% under the lower limit, whereas 18% of the test results were supratherapeutic, of which 40/69 more than 15% above the upper limit. CONCLUSION: In this cohort of critically ill patients, therapeutic APTT values were reached within 24 hours in 56% of the patients. We conclude that intravenous UFH therapy can be improved in critically ill patients. PMID- 24218421 TI - Influenza vaccination coverage in patients treated with chemotherapy: current clinical practice. AB - BACKGROUND: Influenza virus vaccination is recommended for patients treated with chemotherapy. Little is known about vaccination coverage in these patients. METHODS: Vaccination coverage in the Netherlands was analysed by questionnaires completed by general practitioners, within a catchment area of 1.3 million people, in the period 2010-2011. RESULTS: Of 433 eligible adult patients treated with chemotherapy for breast or colorectal cancer, 144 patients gave permission for us to approach their general practitioner with a questionnaire. General practitioners were asked about vaccination coverage, awareness of recommendations and their opinion about the responsibility for vaccination. We received 114 (79%) completed questionnaires. Sixty-seven out of 114 patients (59%) were vaccinated against influenza. Forty-four (66%) of these patients also had an indication for vaccination based on age (age >=60 years). According to 48% of the general practitioners, the responsibility for vaccination belongs to the competence of the treating medical oncologist. CONCLUSION: Influenza vaccination coverage is limited to 59% of patients treated with chemotherapy. Guidelines for responsibility (general practitioner or medical oncologist) may increase the vaccination rate of cancer patients. PMID- 24218422 TI - Fasciola hepatica as a cause of jaundice after chewing khat: a case report. AB - Fasciola hepatica is a worldwide distributed zoonotic trematode incidentally infecting humans. Although often symptomatic, fascioliasis can cause a wide spectrum of disease. The diagnosis can be established by stool examination detecting ova of the parasite, although serological testing has a higher sensitivity and specificity in the acute phase of disease. This case presents a 24-year-old Somalian man admitted with jaundice and abdominal discomfort due to fascioliasis after chewing khat. The patient was treated successfully with a single dose of triclabendazole. PMID- 24218423 TI - A male with extensive renal vein thrombosis. PMID- 24218424 TI - Skin lesions in a patient with head and neck cancer. PMID- 24218425 TI - Bilateral abdominal mass. PMID- 24218426 TI - A diagnosis on the basis of a blood smear. PMID- 24218427 TI - Red cell distribution width as predictor for mortality in critically ill patients. AB - BACKGROUND: The objective of this study was to evaluate whether the red cell distribution width (RDW) is a significant risk factor for hospital mortality in critically ill patients and to investigate whether RDW is a parameter indicating inflammation, or a risk factor independent of inflammation. METHODS: We studied all patients admitted to a ten-bed mixed intensive care unit in the Netherlands between May 2005 and December 2011 for whom RDW was available, and who had not received a blood transfusion in the preceding three months. Inflammation was measured by C-reactive protein and leucocyte count. Analyses included correlation, logistic regression analysis, and receiveroperating characteristic (ROC) curves. RESULTS: We included 2915 patients, of whom 387 (13.3%) did not survive to hospital discharge. In univariate analysis higher RDW values were associated with increased hospital mortality. In multivariate analysis RDW remained an independent risk factor for mortality after correction for APACHE II score, age, admission type and mechanical ventilation (odds ratio 1.04, 95% confidence interval 1.02-1.06, for each femtolitre of RDW). Adding RDW to APACHE II, however, increased the area under the ROC curve marginally (from 0.845 to 0.849, p<0.001). RDW was not correlated with C-reactive protein and leucocyte count, refuting the hypothesis that the association between RDW and outcome is mediated through inflammation. CONCLUSION: In critically ill patients, the RDW on ICU admission was an independent predictor of mortality. Since RDW was not correlated with inflammation, the underlying mechanism of this association warrants further investigation. PMID- 24218428 TI - Cervical dysplasia associated with the use of natalizumab. PMID- 24218429 TI - Cyanide intoxication by apricot kernel ingestion as complimentary cancer therapy. PMID- 24218430 TI - Adrenal signaling in heart failure: something more than a distant ship's smoke on the horizon. PMID- 24218432 TI - Long-term antihypertensive treatment fails to improve E/e' despite regression of left ventricular mass: an Anglo-Scandinavian cardiac outcomes trial substudy. AB - Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the short term, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine+/-perindopril-based or an atenolol+/-bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (~1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5-116.8; atenolol: 122.9-117.5; P<0.001 for both). Conversely, tissue Doppler diastolic indices did not change in the amlodipine+/-perindopril-based regimen (E/e', 7.5 7.6 cm/s; P=not significant), but deteriorated in the atenolol+/ bendroflumethiazide-based regimen (E/e', 8.0-8.5 cm/s; P<0.01). Despite regression of left ventricular hypertrophy, there was no associated improvement in diastolic function. In fact, long-term treatment with atenolol+/ bendroflumethiazide resulted in a progressive deterioration in E/e'. This may be a factor contributing to the previously described worse clinical outcome in patients treated with atenolol+/-bendroflumethiazide compared with amlodipine+/ perindopril. PMID- 24218431 TI - Intermedin in paraventricular nucleus attenuates sympathetic activity and blood pressure via nitric oxide in hypertensive rats. AB - Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N(omega)-propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride. AM22-52 increased renal sympathetic nerve activity and mean arterial pressure in 2K1C rats but not in sham-operated rats, whereas calcitonin/calcitonin gene-related peptide receptor antagonist calcitonin/calcitonin gene-related peptide 8-37 had no significant effect. CRLR and RAMP3 mRNA, as well as CRLR, RAMP2, and RAMP3 protein expressions, in the PVN were increased in 2K1C rats. Microinjection of IMD into the PVN increased the NO metabolites (NOx) level in the PVN in 2K1C rats, which was prevented by AM22-52. Chronic PVN infusion of IMD reduced, but AM22-52 increased, blood pressure in conscious 2K1C rats. These results indicate that IMD in the PVN inhibits sympathetic activity and attenuates hypertension in 2K1C rats, which are mediated by adrenomedullin receptors (CRLR/RAMP2 or CRLR/RAMP3) and its downstream NO. PMID- 24218433 TI - Role of GRK4 in the regulation of arterial AT1 receptor in hypertension. AB - G-protein-coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin-angiotensin system functions, cause sodium retention and increase blood pressure. Whether GRK4 and the angiotensin type 1 receptor (AT(1)R) interact in the aorta is not known. We report that GRK4 is expressed in vascular smooth muscle cells of the aorta. Heterologous expression of the GRK4gamma variant 142V in A10 cells increased AT(1)R protein expression and AT(1)R-mediated increase in intracellular calcium concentration. The increase in AT(1)R expression was related to an increase in AT(1)R mRNA expression via the NF-kappaB pathway. As compared with control, cells expressing GRK4gamma 142V had greater NF-kappaB activity with more NF-kappaB bound to the AT(1)R promoter. The increased AT(1)R expression in cells expressing GRK4gamma 142V was also associated with decreased AT(1)R degradation, which may be ascribed to lower AT(1)R phosphorylation. There was a direct interaction between GRK4gamma and AT(1)R that was decreased by GRK4gamma 142V. The regulation of AT(1)R expression by GRK4gamma 142V in A10 cells was confirmed in GRK4gamma 142V transgenic mice; AT(1)R expression was higher in the aorta of GRK4gamma 142V transgenic mice than control GRK4gamma wild-type mice. Angiotensin II-mediated vasoconstriction of the aorta was also higher in GRK4gamma 142V than in wild-type transgenic mice. This study provides a mechanism by which GRK4, via regulation of arterial AT(1)R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension. PMID- 24218434 TI - Plasma soluble (pro)renin receptor is independent of plasma renin, prorenin, and aldosterone concentrations but is affected by ethnicity. AB - A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ~25% lower in black than in white subjects, whereas renin concentrations were ~40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ~12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ~10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity. PMID- 24218436 TI - An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. AB - Adrenal venous sampling is recommended by current guidelines to identify surgically curable causes of hyperaldosteronism but remains markedly underused. Key factors contributing to the poor use of adrenal venous sampling include the prevailing perceptions that it is a technically challenging procedure, difficult to interpret, and can be complicated by adrenal vein rupture. In addition, the lack of uniformly accepted standards for the performance of adrenal venous sampling contributes to its limited use. Hence, an international panel of experts working at major referral centers was assembled to provide updated advice on how to perform and interpret adrenal venous sampling. To this end, they were asked to use the PICO (Patient or Problem, Intervention, Control or comparison, Outcome) strategy to gather relevant information from the literature and to rely on their own experience. The level of evidence/recommendation was provided according to American Heart Association gradings whenever possible. A consensus was reached on several key issues, including the selection and preparation of the patients for adrenal venous sampling, the procedure for its optimal performance, and the interpretation of its results for diagnostic purposes even in the most challenging cases. PMID- 24218435 TI - Negative impact of beta-arrestin-1 on post-myocardial infarction heart failure via cardiac and adrenal-dependent neurohormonal mechanisms. AB - beta-Arrestin (betaarr)-1 and beta-arrestin-2 (betaarrs) are universal G-protein coupled receptor adapter proteins that negatively regulate cardiac beta adrenergic receptor (betaAR) function via betaAR desensitization and downregulation. In addition, they mediate G-protein-independent betaAR signaling, which might be beneficial, for example, antiapoptotic, for the heart. However, the specific role(s) of each betaarr isoform in cardiac betaAR dysfunction, the molecular hallmark of chronic heart failure (HF), remains unknown. Furthermore, adrenal betaarr1 exacerbates HF by chronically enhancing adrenal production and hence circulating levels of aldosterone and catecholamines. Herein, we sought to delineate specific roles of betaarr1 in post-myocardial infarction (MI) HF by testing the effects of betaarr1 genetic deletion on normal and post-MI cardiac function and morphology. We studied betaarr1 knockout (betaarr1KO) mice alongside wild-type controls under normal conditions and after surgical MI. Normal (sham operated) betaarr1KO mice display enhanced betaAR-dependent contractility and post-MI betaarr1KO mice enhanced overall cardiac function (and betaAR-dependent contractility) compared with wild type. Post-MI betaarr1KO mice also show increased survival and decreased cardiac infarct size, apoptosis, and adverse remodeling, as well as circulating catecholamines and aldosterone, compared with post-MI wild type. The underlying mechanisms, on one hand, improved cardiac betaAR signaling and function, as evidenced by increased betaAR density and procontractile signaling, via reduced cardiac betaAR desensitization because of cardiac betaarr1 absence, and, on the other hand, decreased production leading to lower circulating levels of catecholamines and aldosterone because of adrenal betaarr1 absence. Thus, betaarr1, via both cardiac and adrenal effects, is detrimental for cardiac structure and function and significantly exacerbates post MI HF. PMID- 24218437 TI - In utero diagnosis of long QT syndrome by magnetocardiography. AB - BACKGROUND: The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS. METHODS AND RESULTS: We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2 degrees atrioventricular block, ventricular tachycardia, heart rate < 3(rd) percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQ1, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT >= 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype. CONCLUSIONS: Corrected QT prolongation (>=490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (>=620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS. PMID- 24218438 TI - Novel role of silent information regulator 1 in myocardial ischemia. PMID- 24218439 TI - Approach to the patient with peripheral arterial disease. PMID- 24218440 TI - Renal denervation therapy for hypertension. PMID- 24218441 TI - ECG response: November 12, 2013. PMID- 24218442 TI - Bilateral giant coronary aneurysms in Kawasaki disease: how difficult can it be? PMID- 24218443 TI - Clear morphological depiction of cor triatriatum in a child by transthoracic 3 dimensional echocardiography. PMID- 24218445 TI - Letter by Singh Regarding Article, "Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children". PMID- 24218446 TI - Letter by Magalhaes et al regarding article, "Long-term survival and repeat coronary revascularization in dialysis patients after surgical and percutaneous coronary revascularization with drug-eluting and bare metal stents in the United States". PMID- 24218447 TI - Response to letter regarding article, "Long-term survival and repeat coronary revascularization in dialysis patients after surgical and percutaneous coronary revascularization with drug-eluting and bare metal stents in the United States". PMID- 24218449 TI - Enhanced endoplasmic reticulum entry of tumor antigen is crucial for cross presentation induced by dendritic cell-targeted vaccination. AB - Efficient cross-presentation of protein Ags to CTLs by dendritic cells (DCs) is essential for the success of prophylactic and therapeutic vaccines. In this study, we report a previously underappreciated pathway involving Ag entry into the endoplasmic reticulum (ER) critically needed for T cell cross-priming induced by a DC-targeted vaccine. Directing the clinically relevant, melanoma Ag gp100 to mouse-derived DCs by molecular adjuvant and chaperone Grp170 substantially facilitates Ag access to the ER. Grp170 also strengthens the interaction of internalized protein Ag with molecular components involved in ER-associated protein dislocation and/or degradation, which culminates in cytosolic translocation for proteasome-dependent degradation and processing. Targeted disruption of protein retrotranslocation causes exclusive ER retention of tumor Ag in mouse bone marrow-derived DCs and splenic CD8(+) DCs. This results in the blockade of Ag ubiquitination and processing, which abrogates the priming of Ag specific CD8(+) T cells in vitro and in vivo. Therefore, the improved ER entry of tumor Ag serves as a molecular basis for the superior cross-presenting capacity of Grp170-based vaccine platform. The ER access and retrotranslocation represents a distinct pathway that operates within DCs for cross-presentation and is required for the activation of Ag-specific CTLs by certain vaccines. These results also reinforce the importance of the ER-associated protein quality control machinery and the mode of the Ag delivery in regulating DC-elicited immune outcomes. PMID- 24218450 TI - CD2-associated protein regulates plasmacytoid dendritic cell migration, but is dispensable for their development and cytokine production. AB - Plasmacytoid dendritic cells (pDCs) are a dendritic cell subset that secrete type I IFNs in response to microbial stimuli. The scaffold protein, CD2-associated protein (CD2AP), is a marker of human pDCs as it is highly expressed in this cell type. Recently, in human pDCs, decreased CD2AP expression appeared to enhance the production of type I IFNs via an inhibitory receptor-induced signaling cascade. In this study, we sought to determine the role of CD2AP in murine pDCs using CD2AP knockout (KO) mice. CD2AP was dispensable for the development of pDCs and for the upregulation of activation markers following stimulation. Loss of CD2AP expression did not affect the production of type I IFNs stimulated by TLR ligation, and only slightly impaired type I IFN production when inhibitory pathways were engaged in vitro. This was also confirmed by showing that CD2AP deficiency did not influence type I IFN production by pDCs in vivo. Because CD2AP plays a role in regulating actin dynamics, we examined the actin cytoskeleton in pDCs and found that activated CD2AP KO pDCs had significantly higher levels of actin polymerization than wild-type pDCs. Using two different inflammation models, we found that CD2AP KO pDCs have a defect in lymph node migration, correlating with the defects in actin dynamics. Our work excludes a role for CD2AP in the regulation of type I IFNs in pDCs, and suggests that the major function of CD2AP is on the actin cytoskeleton, affecting migration to local lymph nodes under conditions of inflammation. PMID- 24218451 TI - The exonuclease Trex1 restrains macrophage proinflammatory activation. AB - The three-prime repair exonuclease 1 (TREX1) is the most abundant exonuclease in mammalian cells. Mutations in Trex1 gene are being linked to the development of Aicardi-Goutieres syndrome, an inflammatory disease of the brain, and systemic lupus erythematosus. In clinical cases and in a Trex1-deficient murine model, chronic production of type I IFN plays a pathogenic role. In this study, we demonstrate that Trex1(-/-) mice present inflammatory signatures in many different organs, including the brain. Trex1 is highly induced in macrophages in response to proinflammatory stimuli, including TLR7 and TLR9 ligands. Our findings show that, in the absence of Trex1, macrophages displayed an exacerbated proinflammatory response. More specifically, following proinflammatory stimulation, Trex1(-/-) macrophages exhibited an increased TNF-alpha and IFN alpha production, higher levels of CD86, and increased Ag presentation to CD4(+) T cells, as well as an impaired apoptotic T cell clearance. These results evidence an unrevealed function of the Trex1 as a negative regulator of macrophage inflammatory activation and demonstrate that macrophages play a major role in diseases associated with Trex1 mutations, which contributes to the understanding of inflammatory signature in these diseases. PMID- 24218452 TI - Adenylyl cyclase 6 activation negatively regulates TLR4 signaling through lipid raft-mediated endocytosis. AB - Proper intracellular localization of TLRs is essential for their signaling and biological function. Endocytosis constitutes a key step in protein turnover, as well as maintenance of TLR localization in plasma membrane and intracellular compartments, and thus provides important regulating points to their signaling. In this study, we demonstrate that adenylyl cyclase (AC) activation attenuates TLR4 signaling in a murine macrophage cell line (RAW 264.7) and bone marrow derived macrophages when stimulated with LPS. We further show that the AC6 isoform plays a key role in negative regulation of TLR4 signaling by promoting protein degradation. TLR4 is normally endocytosed through the clathrin-mediated pathway, but concomitant AC6 activation shifts it to lipid raft-mediated endocytosis, which accelerates degradation of TLR4 and suppresses downstream signaling. Our studies unveil a new mechanism of negative regulation of TLR4 signaling through AC6-mediated endocytosis, which might provide a novel therapeutic approach for limiting inflammatory and autoimmune diseases. PMID- 24218453 TI - Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. AB - Foxp3(+) T regulatory cells (Tregs) are critically important for the maintenance of immunological tolerance, immune homeostasis, and prevention of autoimmunity. Dendritic cells (DCs) are one of the major targets of Treg-mediated suppression. Some studies have suggested that Treg-mediated suppression of DC function is mediated by the interaction of CTLA-4 on Tregs with CD80/CD86 on the DCs resulting in downregulation of CD80/CD86 expression and a decrease in costimulation. We have re-examined the effects of Tregs on mouse DC function in a model in which Ag-specific, induced Tregs (iTregs) are cocultured with DCs in the absence of T effector cells. iTreg-treated DCs are markedly defective in their capacity to activate naive T cells. iTregs from CTLA-4-deficient mice failed to induce downregulation of CD80/CD86, but DCs treated with CTLA-4-deficient iTregs still exhibited impaired capacity to activate naive T cells. The iTreg-induced defect in DC function could be completely reversed by anti-IL-10, and IL-10 deficient iTregs failed to downregulate DC function. iTreg-treated DCs expressed high levels of MARCH1, an E3 ubiquitin ligase, recently found to degrade CD86 and MHC class II on the DCs and expressed lower levels of CD83, a molecule involved in neutralizing the function of MARCH1. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. Taken together, these studies demonstrate that a major suppressive mechanism of DC function by iTregs is secondary to the effects of IL-10 on MARCH1 and CD83 expression. PMID- 24218454 TI - Temporal requirements for B cells in the establishment of CD4 T cell memory. AB - CD4 T cell memory generation is shaped by a number of factors, including the strength and duration of TCR signaling, as well as the priming environment, all of which can be modified by B cells. Studies using B cell-deficient mice indicate B cells play a critical role in generating effector and memory CD4 T cells; however, when and how B cells are acting to promote these responses has not yet been ascertained. In this study, we use anti-CD20 Ab depletion of B cells at different times following Listeria monocytogenes infection to show that B cells are necessary for the induction of optimal CD4 T cell memory, but not for the transition and maintenance of this population. Importantly, the prerequisite of B cells early postinfection is partially dependent on their expression of MHC class II. B cells are not only required during the priming phase, but also necessary for the initiation of robust secondary responses by memory CD4 T cells. Interestingly, the requirement during the recall response is independent of B cell Ag presentation. Overall, these studies demonstrate the temporally and functionally distinct roles for B cells in regulating CD4 T cell responses. PMID- 24218455 TI - A role for IRF8 in B cell anergy. AB - B cell central tolerance is a process through which self-reactive B cells are removed from the B cell repertoire. Self-reactive B cells are generally removed by receptor editing in the bone marrow and by anergy induction in the periphery. IRF8 is a critical transcriptional regulator of immune system development and function. A recent study showed that marginal zone B cell and B1 B cell populations are dramatically increased in IRF8-deficient mice, indicating that there are B cell-developmental defects in the absence of IRF8. In this article, we report that mice deficient for IRF8 produced anti-dsDNA Abs. Using a hen egg lysozyme double-transgenic model, we further demonstrate that B cell anergy was breached in IRF8-deficient mice. Although anergic B cells in the IRF8-proficient background were blocked at the transitional stage of development, anergic B cells in the IRF8-deficient background were able to mature further, which allowed them to regain responses to Ag stimulation. Interestingly, our results show that IRF8 deficient B cells were more sensitive to Ag stimulation and were resistant to Ag induced cell death. Moreover, our results show that IRF8 was expressed at a high level in the anergic B cells, and an elevated level of IRF8 promoted apoptosis in the transitional B cells. Thus, our findings reveal a previously unrecognized function of IRF8 in B cell anergy induction. PMID- 24218457 TI - Calcineurin-Rcan1 interaction contributes to stem cell factor-mediated mast cell activation. AB - The receptor for stem cell factor (SCF) is expressed on mast cells and hematopoietic progenitors. SCF-induced signaling pathways remain incompletely defined. In this study, we identified calcineurin and regulator of calcineurin 1 (Rcan1) as novel components in SCF signaling. Calcineurin activity was induced in SCF-stimulated primary mouse and human mast cells. NFAT was activated by SCF in bone marrow-derived mast cells (BMMCs) and mouse bone marrow cells, which contain hematopoietic progenitors. SCF-mediated activation also induced expression of Rcan1 in BMMCs. Rcan1-deficient BMMCs showed increased calcineurin activity and enhanced transcriptional activity of NF-kappaB and NFAT, resulting in increased IL-6 and TNF production following SCF stimulation. These results suggest that Rcan1 suppresses SCF-induced activation of calcineurin and NF-kappaB. We further demonstrated that SCF-induced Rcan1 expression is dependent on the transcription factor early growth response 1 (Egr1). Interestingly, SCF-induced Egr1 was also suppressed by Rcan1, suggesting a negative regulatory loop between Egr1 and Rcan1. Together, our findings revealed that calcineurin contributes to SCF induced signaling, leading to NFAT activation, which, together with NF-kappaB and Egr1, is suppressed by Rcan1. Considering the wide range of biological functions of SCF, these novel regulatory mechanisms in SCF signaling may have broad implications. PMID- 24218456 TI - Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming. AB - Anaplastic lymphoma kinase (ALK), physiologically expressed only by nervous system cells, displays a remarkable capacity to transform CD4(+) T lymphocytes and other types of nonneural cells. In this study, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK expressed in T cell lymphomas (TCLs), closely resembles cell activation induced by IL-2, the key cytokine supporting growth and survival of normal CD4(+) T lymphocytes. Direct comparison of gene expression by ALK(+) TCL cells treated with an ALK inhibitor and IL-2-dependent ALK(-) TCL cells stimulated with the cytokine revealed a very similar, albeit inverse, gene-regulation pattern. Depending on the analysis method, up to 67% of the affected genes were modulated in common by NPM/ALK and IL-2. Based on the gene expression patterns, Jak/STAT- and IL-2-signaling pathways topped the list of pathways identified as affected by both IL-2 and NPM/ALK. The expression dependence on NPM/ALK and IL-2 of the five selected genes CD25 (IL-2Ralpha), Egr-1, Fosl-1, SOCS3, and Irf-4-was confirmed at the protein level. In both ALK(+) TCL and IL-2-stimulated ALK(-) TCL cells, CD25, SOCS3, and Irf-4 genes were activated predominantly by the STAT5 and STAT3 transcription factors, whereas transcription of Egr-1 and Fosl-1 was induced by the MEK-ERK pathway. Finally, we found that Egr-1, a protein not associated previously with either IL-2 or ALK, contributes to the cell proliferation. These findings indicate that NPM/ALK transforms the target CD4(+) T lymphocytes, at least in part, by using the pre-existing, IL-2-dependent signaling pathways. PMID- 24218458 TI - Sick sinus syndrome in HCN1-deficient mice. AB - BACKGROUND: Sinus node dysfunction (SND) is a major clinically relevant disease that is associated with sudden cardiac death and requires surgical implantation of electric pacemaker devices. Frequently, SND occurs in heart failure and hypertension, conditions that lead to electric instability of the heart. Although the pathologies of acquired SND have been studied extensively, little is known about the molecular and cellular mechanisms that cause congenital SND. METHODS AND RESULTS: Here, we show that the HCN1 protein is highly expressed in the sinoatrial node and is colocalized with HCN4, the main sinoatrial pacemaker channel isoform. To characterize the cardiac phenotype of HCN1-deficient mice, a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparation, telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology was performed. On the basis of these experiments we demonstrate that mice lacking the pacemaker channel HCN1 display congenital SND characterized by bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses. As a consequence of SND, HCN1 deficient mice display a severely reduced cardiac output. CONCLUSIONS: We propose that HCN1 stabilizes the leading pacemaker region within the sinoatrial node and hence is crucial for stable heart rate and regular beat-to-beat variation. Furthermore, we suggest that HCN1-deficient mice may be a valuable genetic disease model for human SND. PMID- 24218459 TI - SUPPORTing premature infants. PMID- 24218461 TI - Epidemiology of bacteremia in febrile infants in the United States. AB - BACKGROUND: Fever in infants is a common clinical dilemma. The objective of this study was to present data from hospital systems across the northeast, southeast, mid-west, and western United States to identify the pathogens causing bacteremia in febrile infants admitted to general care units. METHODS: This was a retrospective review of positive blood culture results in febrile infants aged <=90 days admitted to a general care unit across 6 hospital systems. Data were collected from January 1, 2006 through December 31, 2012 from emergency departments and general inpatient units. Cultures from ICUs, central lines, or infants who had complex comorbidities were excluded, as were repeat cultures positive for the same bacteria. Common contaminants were considered pathogens if they were treated as such. RESULTS: We identified 181 cases of bacteremia in 177 infants. The most common pathogen was Escherichia coli (42%), followed by group B Streptococcus (23%). Streptococcus pneumoniae was more likely in older infants (P = .01). Non-low-risk bacteremic infants were more likely to have E. coli or group B Streptococcus than low-risk bacteremic infants. We identified no cases of Listeria monocytogenes. Variation between sites was minimal. CONCLUSIONS: This is the largest and most geographically diverse study to date examining the epidemiology of bacteremia in infants. We suggest E. coli is the most common cause of bacteremia in previously healthy febrile infants admitted to a general inpatient unit. We identified no cases of L monocytogenes and question whether empirical therapy remains necessary for this pathogen. PMID- 24218460 TI - Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth. AB - OBJECTIVE: Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low alpha-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. METHODS: Ninety-three infants <27 weeks' gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-alpha-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. RESULTS: Eighty-eight infants received the study drug and were included in the analyses. The alpha-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in gamma-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had alpha-tocopherol levels <0.5 mg/dL. CONCLUSIONS: A 50-IU/kg dose of vitamin E raised serum alpha-tocopherol levels, but to consistently achieve alpha-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed. PMID- 24218462 TI - Cough and cold medication adverse events after market withdrawal and labeling revision. AB - BACKGROUND: In October 2007, manufacturers voluntarily withdrew over-the-counter (OTC) infant cough and cold medications (CCMs) from the US market. A year later, manufacturers announced OTC CCM labeling would be revised to warn against OTC CCM use by children aged <4 years. We determined whether emergency department (ED) visits for CCM adverse drug events (ADEs) declined after these interventions. METHODS: We used National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance data from 2004 to 2011 to estimate the number of ED visits for CCM ADEs before and after each intervention. RESULTS: Among children aged <2 years, ED visits for CCM ADEs decreased from 4.1% of all ADE ED visits before the market withdrawal to 2.4% of all ADE visits afterward (difference in proportion: -1.7%, 95% confidence interval [CI]: -2.7% to -0.6%). Among children aged 2 to 3 years, ED visits for CCM ADEs decreased from 9.5% of all ADE ED visits before the labeling revision announcement to 6.5% of all ADE visits afterward (difference in proportion: -3.0%, 95% CI: -5.4% to -0.6%). Unsupervised ingestions accounted for 64.3% (95% CI: 51.1% to 77.5%) of CCM ADE ED visits involving children aged <2 years after the withdrawal and 88.8% (95% CI: 83.8% to 93.8%) of visits involving children aged 2 to 3 years after the labeling revision announcement. CONCLUSIONS: After a voluntary market withdrawal and labeling revision, ED visits for CCM ADEs declined among children aged <2 years and 2 to 3 years relative to ADE ED visits for all drugs. Interventions addressing unsupervised ingestions are needed to reduce CCM ADEs. PMID- 24218463 TI - Vaccine-preventable disease among homeschooled children: two cases of tetanus in Oklahoma. AB - Homeschooled children represent an increasing proportion of school-aged children in the United States. Immunization rates among homeschooled children are largely unknown because they are usually not subject to state-based school-entry vaccination requirements. Geographic foci of underimmunized children can increase the risk for outbreaks of vaccine-preventable diseases. In 2012, 2 cases of tetanus were reported in Oklahoma; both cases involved homeschooled children without documentation of diphtheria-tetanus-acellular pertussis vaccination. We describe the characteristics of both patients and outline innovative outreach measures with the potential to increase vaccination access and coverage among homeschooled children. PMID- 24218464 TI - Development and evaluation of global child health educational modules. AB - OBJECTIVES: To determine if a standardized global child health (GCH) modular course for pediatric residents leads to satisfaction, learning, and behavior change. METHODS: Four 1-hour interactive GCH modules were developed addressing priority GCH topics. "Site champions" from 4 Canadian institutions delivered modules to pediatric residents from their respective programs during academic half-days. A pre-post, mixed methods evaluation incorporated satisfaction surveys, multiple-choice knowledge tests, and focus group discussions involving residents and satisfaction surveys from program directors. RESULTS: A total of 125 trainees participated in >=1 module. Satisfaction levels were high. Focus group participants reported high satisfaction with the concepts taught and the dynamic, participatory approach used, which incorporated multimedia resources. Mean scores on knowledge tests increased significantly postintervention for 3 of the 4 modules (P < .001), and residents cited increases in their practical knowledge, global health awareness, and motivation to learn about global health. Program directors unanimously agreed that the modules were relevant, interesting, and could be integrated within existing formal training time. CONCLUSIONS: A relatively short, participatory, foundational GCH modular curriculum facilitated knowledge acquisition and attitude change. It could be scaled up and serve as a model for other standardized North American curricula. PMID- 24218465 TI - Resuscitation of preterm neonates with limited versus high oxygen strategy. AB - OBJECTIVE: To determine whether a limited oxygen strategy (LOX) versus a high oxygen strategy (HOX) during delivery room resuscitation decreases oxidative stress in preterm neonates. METHODS: A randomized trial of neonates of 24 to 34 weeks' gestational age (GA) who received resuscitation was performed. LOX neonates received room air as the initial resuscitation gas, and fraction of inspired oxygen (Fio2) was adjusted by 10% every 30 seconds to achieve target preductal oxygen saturations (Spo2) as described by the 2010 Neonatal Resuscitation Program guidelines. HOX neonates received 100% O2 as initial resuscitation gas, and Fio2 was adjusted by 10% to keep preductal Spo2 at 85% to 94%. Total hydroperoxide (TH), biological antioxidant potential (BAP), and the oxidative balance ratio (BAP/TH) were analyzed in cord blood and the first hour of life. Secondary outcomes included delivery room interventions, respiratory support on NICU admission, and short-term morbidities. RESULTS: Forty-four LOX (GA: 30 +/- 3 weeks; birth weight: 1678 +/- 634 g) and 44 HOX (GA: 30 +/- 3 weeks; birth weight: 1463 +/- 606 g) neonates were included. LOX decreased integrated excess oxygen (?Fio2 * time [min]) in the delivery room compared with HOX (401 +/- 151 vs 662 +/- 249; P < .01). At 1 hour of life, BAP/TH was 60% higher for LOX versus HOX neonates (13 [9-16] vs 8 [6-9]) uM/U.CARR, P < .01). LOX decreased ventilator days (3 [0-64] vs 8 [0-96]; P < .05) and reduced the incidence of bronchopulmonary dysplasia (7% vs 25%; P < .05). CONCLUSIONS: LOX is feasible and results in less oxygen exposure, lower oxidative stress, and decreased respiratory morbidities and thus is a reasonable alternative for resuscitation of preterm neonates in the delivery room. PMID- 24218466 TI - A collaborative system to improve compartment syndrome recognition. AB - BACKGROUND AND OBJECTIVE: Acute compartment syndrome (ACS) is a rare but serious complication of extremity injury that can cause permanent damage or death. ACS development is variable and unpredictable, and delay in recognition or treatment of ACS can lead to significant morbidity. Our objective was to create a reliable system for recognition of patients at risk and monitoring for ACS that could withstand frequent provider turnover. METHODS: Using the Model for Improvement, we identified key drivers and failure modes for 2 processes: resident and nurse practitioner proper order entry and bedside nurse proper documentation of monitoring. Interventions were tested in frequent plan-do-study-act cycles. Effective interventions were used in combination to test for sustainability. RESULTS: Proper order entry increased from 23% at baseline to 90%. Proper documentation for patients with correct orders increased from 15% to 70%. Individual interventions, including pocket card distribution, electronic medical record order set, and direct discussion by team leaders, were associated with improvement among residents but were not sustained with team turnover. Incorporating all 4 individual interventions into the on-boarding process for residents produced consistent success. Nursing documentation improved with education and maintenance of proper order entry. CONCLUSIONS: We built a reliable, sustainable system to recognize and monitor patients at risk for ACS. Interventions designed to minimally disrupt existing workflows were individually associated with improvement. We achieved sustainability through staff turnover when we incorporated the interventions into routine orientation for new staff. Hospitals can use existing orders and protocols to sustain surveillance for ACS and other acute conditions. PMID- 24218467 TI - Sexual risk taking and bullying among adolescents. AB - BACKGROUND: Psychological and educational correlates of bullying have been explored extensively. However, little information is available about the link between bullying and sexual risk-taking behaviors among adolescents, though for some youth it may be that sexual risk taking emerges in response to bullying involvement. Associations for both heterosexual youth and those who identify as gay, lesbian, bisexual, transgender, or questioning (GLBTQ) should be considered, as should the influence of victimization exposures in other domains. Accordingly, associations among bullying, other victimization forms, and sexual risk-taking behaviors were examined among adolescents with particular consideration to sexual orientation. METHODS: A sample of 8687 high school students completed the Dane County Youth Survey, a countywide survey administered high school students from 24 schools. Participants were asked questions about their bullying involvement and sexual risk-taking behaviors (ie, engaging in casual sex and having sex while under the influence of alcohol or drugs). RESULTS: Results indicated that bullies and bully-victims were more likely to engage in casual sex and sex under the influence. In multivariate analyses, these findings held even after controlling for demographic characteristics and victimization exposures in other domains, but primarily for heterosexual youth. CONCLUSIONS: Bullies and bully-victims engaged in more sexual risk-taking behaviors, although patterns of association varied by sexual orientation. Bullying prevention programs and programs aimed at reducing unhealthy sexual practices should consider a broader stress and coping perspective and address the possible link between the stress of bullying involvement and maladaptive coping responses. PMID- 24218468 TI - Neonatal death suspected to be from sepsis was found to be kernicterus with G6PD deficiency. AB - We cared for a term male infant born to Burmese immigrants. At about 24 hours a total serum bilirubin (TSB) was 9.3 mg/dL, and phototherapy was begun. It was stopped 48 hours later, with a TSB of 10.9 mg/dL, and he was discharged from the hospital with an appointment for a repeat TSB check 48 hours later. A few hours before the appointment he became listless and apneic, and his parents took him to the emergency department of the regional children's hospital, where sepsis was suspected. The TSB was 41 mg/dL. He died 4 hours later, despite intensive care efforts, with opisthotonus and refractory hypotension. Blood drawn before the exchange transfusion had low glucose-6-phosphate dehydrogenase (G6PD) enzymatic activity, and sequencing of the G6PD gene revealed the G6PD Mahidol mutation (c.487G>A). Cultures and postmortem examination did not demonstrate an infectious process, but kernicterus was present. Acute kernicterus can mimic septic shock. PMID- 24218470 TI - QTc interval prolongation and severe apneas associated with a change in infant positioning. AB - For more than a decade there has been considerable interest in the role of QT interval prolongation in the pathogenesis of sudden infant death syndrome. It has been proposed that the QT interval is a surrogate marker for autonomic instability and can be used to identify infants at risk for significant morbidity and mortality, including sudden infant death syndrome. We present the case of an infant that experienced a significant increase in his QTc, as detected by continuous QTc monitoring in the NICU after repositioning from a supine to prone position. This increase from a 413 +/- 6 millisecond baseline average to 500 milliseconds was sustained for 2 hours and associated with clinically relevant apnea that ultimately required repositioning of the infant back to the supine position. Repositioning resulted in an immediate decrease of the QTc back to the previous baseline and termination of the apneic events. This case demonstrates an example of how the use of continuous QTc monitoring in the NICU setting may be used to detect QTc-accentuating factors in real time and identify situations that cause perturbations in an infant's autonomic nervous system. PMID- 24218469 TI - Longitudinal validation of a tool for asthma self-monitoring. AB - OBJECTIVES: To establish longitudinal validation of a new tool, the Asthma Symptom Tracker (AST). AST combines weekly use of the Asthma Control Test with a color-coded graph for visual trending. METHODS: Prospective cohort study of children age 2 to 18 years admitted for asthma. Parents or children (n = 210) completed baseline AST assessments during hospitalization, then over 6 months after discharge. Concurrent with the first 5 AST assessments, the Asthma Control Questionnaire (ACQ) was administered for comparison. RESULTS: Test-retest reliability (intraclass correlation) was moderate, with a small longitudinal variation of AST measurements within subjects during follow-ups. Internal consistency was strong at baseline (Cronbach's alpha 0.70) and during follow-ups (Cronbach's alpha 0.82-0.90). Criterion validity demonstrated a significant correlation between AST and ACQ scores at baseline (r = -0.80, P < .01) and during follow-ups (r = -0.64, -0.72, -0.63, and -0.69). The AST was responsive to change over time; an increased ACQ score by 1 point was associated with a decreased AST score by 2.65 points (P < .01) at baseline and 3.11 points (P < .01) during follow-ups. Discriminant validity demonstrated a strong association between decreased AST scores and increased oral corticosteroid use (odds ratio 1.13, 95% confidence interval, 1.10-1.16, P < .01) and increased unscheduled acute asthma visits (odds ratio 1.23, 95% confidence interval, 1.18-1.28, P < .01). CONCLUSIONS: The AST is reliable, valid, and responsive to change over time, and can facilitate ongoing monitoring of asthma control and proactive medical decision-making in children. PMID- 24218472 TI - Overweight adolescents and life events in childhood. AB - OBJECTIVES: To test the association of life events in childhood with overweight risk in adolescence; to examine the effects of chronicity, timing, intensity, valence, and type of life events; and to test potential moderators. METHODS: Mothers of children enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study of Early Child Care and Youth Development responded to the Life Experiences Survey at ages 4, 9, and 11 years. Using logistic regression analysis, we tested the association of experiencing many negative life events with being overweight at age 15 years, controlling for child gender, race/ethnicity, maternal education, and maternal obesity. Child gender, maternal education, maternal obesity, child's ability to delay gratification for food, and maternal sensitivity were tested as moderators. RESULTS: Among the 848 study children (82% non-Hispanic white), experiencing many negative life events was associated with a higher risk of overweight (odds ratio: 1.47 [95% confidence interval: 1.04-2.10]). Greater chronicity and negative valence of the event were associated with greater overweight risk; timing of exposure and maternal reported impact of the event were not. The association was more robust for events related to family physical or mental health and among children of obese mothers and children who waited longer for food. CONCLUSIONS: Children who experience many negative life events are at higher risk of being overweight by age 15 years. Future work should investigate mechanisms involved in this association, particularly those connected to appetitive drive and self regulation; these mechanisms may hold promise for obesity prevention strategies. PMID- 24218471 TI - Potential asphyxia and brainstem abnormalities in sudden and unexpected death in infants. AB - OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, gamma-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (e.g., supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS: We classified cases of sudden infant death into categories relative to a "potential asphyxia" schema in a cohort autopsied at the San Diego County Medical Examiner's Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS: Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P < .05) than those of controls dying of known causes. CONCLUSIONS: We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities. PMID- 24218473 TI - Age at menarche and age at first sexual intercourse: a prospective cohort study. AB - OBJECTIVE: Younger age at menarche (AAM) may put girls at risk for earlier first sexual intercourse (FSI). Young age at FSI has far-reaching negative outcomes. We describe the longitudinal relationship between AAM and FSI in a large prospective birth cohort. METHODS: AAM was collected from 554 girls from the Western Australia (Raine) Pregnancy Cohort Study, prospectively from age 10 or retrospectively at age 14. Age at FSI was collected at ages 17 and 20. Cox regression models describe likelihood of FSI by age and years since menarche for younger (<12 years) and older (>=14 years) AAM relative to average AAM (12-13 years). RESULTS: Girls with younger AAM and average AAM were equally likely to have FSI by age 16 (adjusted hazard ratio [aHR]: 0.90 [95% confidence interval (CI): 0.60-1.35]). FSI by age 16 was less likely among girls with older AAM than those with average AAM (aHR: 0.35 [95% CI: 0.17-0.72]). Girls with younger AAM had a longer median interval between menarche and FSI than girls with average AAM (5.0 years [interquartile range: 4.4-8.5 years] vs 3.7 years [interquartile range: 2.4-5.3 years]). Those with younger AAM were less likely to report FSI within 4 years of menarche than those with average AAM (0-2 years aHR: 0.04 [95% CI: 0.01-0.31]; 2-4 years aHR: 0.36 [95% CI: 0.23-0.55]). By age 20, 429 girls (77.4%) reported FSI. CONCLUSIONS: Younger AAM was not a risk factor for younger age at FSI in this cohort. PMID- 24218474 TI - Catheter dwell time and CLABSIs in neonates with PICCs: a multicenter cohort study. AB - OBJECTIVE: To determine whether the daily risk of central line-associated bloodstream infections (CLABSIs) increases over the dwell time of peripherally inserted central catheters (PICCs) in high-risk neonates. METHODS: Multicenter retrospective cohort including NICU patients with a PICC inserted between January 2005 and June 2010. We calculated incidence rates and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. RESULTS: A total of 4797 PICCs placed in 3967 neonates were included; 149 CLABSIs occurred over 89,946 catheter-days (incidence rate 1.66 per 1000 catheter-days). In unadjusted analysis, PICCs with a dwell time of 8 to 13 days, 14 to 22 days, and >=23 days each had an increased risk of infection compared with PICCs in place for <=7 days (P < .05). In adjusted analysis, the average predicted daily risk of CLABSIs after PICC insertion increased during the first 2 weeks after PICC insertion and remained elevated for the dwell time of the catheter. There was an increased risk of CLABSIs in neonates with concurrent PICCs (adjusted incidence rate ratio 2.04, 1.12-3.71). The incidence of Gram-negative CLABSIs was greater in PICCs with dwell times >50 days (incidence rate ratio 5.26, 2.40 10.66). CONCLUSIONS: The risk of CLABSIs increased during the 2 weeks after PICC insertion and then remained elevated until PICC removal. Clinicians should review PICC necessity daily, optimize catheter maintenance practices, and investigate novel CLABSI prevention strategies in PICCs with prolonged dwell times. PMID- 24218475 TI - Gun violence trends in movies. AB - BACKGROUND: Many scientific studies have shown that the mere presence of guns can increase aggression, an effect dubbed the "weapons effect." The current research examines a potential source of the weapons effect: guns depicted in top-selling films. METHODS: Trained coders identified the presence of violence in each 5 minute film segment for one-half of the top 30 films since 1950 and the presence of guns in violent segments since 1985, the first full year the PG-13 rating (age 13+) was used. PG-13-rated films are among the top-selling films and are especially attractive to youth. RESULTS: Results found that violence in films has more than doubled since 1950, and gun violence in PG-13-rated films has more than tripled since 1985. When the PG-13 rating was introduced, these films contained about as much gun violence as G (general audiences) and PG (parental guidance suggested for young children) films. Since 2009, PG-13-rated films have contained as much or more violence as R-rated films (age 17+) films. CONCLUSIONS: Even if youth do not use guns, these findings suggest that they are exposed to increasing gun violence in top-selling films. By including guns in violent scenes, film producers may be strengthening the weapons effect and providing youth with scripts for using guns. These findings are concerning because many scientific studies have shown that violent films can increase aggression. Violent films are also now easily accessible to youth (e.g., on the Internet and cable). This research suggests that the presence of weapons in films might amplify the effects of violent films on aggression. PMID- 24218477 TI - Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence. AB - Nontypeable Haemophilus influenzae (NTHI) is a leading cause of opportunistic infections of the respiratory tract in children and adults. Although considered an extracellular pathogen, NTHI has been observed repeatedly within and between cells of the human respiratory tract, and these observations have been correlated to symptomatic infection. These findings are intriguing in light of the knowledge that NTHI persists in the respiratory tract despite antibiotic therapy and the development of bactericidal antibodies. We hypothesized that intracellular NTHI avoids, escapes, or neutralizes the endolysosomal pathway and persists within human respiratory epithelial cells and that human IgA1 proteases are required for optimal internalization and persistence of NTHI. Virtually all strains encode a human IgA1 protease gene, igaA, and we previously characterized a novel human IgA1 protease gene, igaB, that is associated with disease-causing strains and is homologous to the IgA1 protease that is unique to pathogenic Neisseria spp. Here, we show that NTHI invades human bronchial epithelial cells in vitro in a lipid raft-independent manner, is subsequently trafficked via the endolysosomal pathway, and is killed in lysosomes after variable durations of persistence. IgaA is required for optimal invasion. IgaB appears to play little or no role in adherence or invasion but is required for optimal intracellular persistence of NTHI. IgaB cleaves lysosome-associated membrane protein 1 (LAMP1) at pHs characteristic of the plasma membrane, early endosome, late endosome, and lysosome. However, neither IgA1 protease inhibits acidification of intracellular vesicles containing NTHI. NTHI IgA1 proteases play important but different roles in NTHI invasion and trafficking in respiratory epithelial cells. PMID- 24218478 TI - Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. AB - As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals. PMID- 24218480 TI - Efficient B cell responses to Borrelia hermsii infection depend on BAFF and BAFFR but not TACI. AB - T cell-independent antibody responses develop rapidly, within 3 to 4 days, and are critical for preventing blood-borne pathogens from evolving into life threatening infections. The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and function. Using a synthetic polysaccharide antigen, it has previously been shown that TACI is critical for T cell-independent antibody responses. To examine the role of BAFFR and TACI in T cell-independent antibody responses to an active infection, we utilized the Borrelia hermsii infection system. In this infection system, T cell-independent responses mediated by the B1b cell subset are critical for controlling bacteremia. We found that B1b cells express BAFFR and TACI and that the surface expression of both receptors is upregulated on B1b cells following exposure to whole B. hermsii cells. Surprisingly, we found that TACI(-/ ) mice are not impaired either in specific antibody responses to B. hermsii or in controlling B. hermsii bacteremia. In contrast, TACI-deficient mice immunized with heat-killed type 3 serotype pneumococcus cells are impaired in generating pneumococcal polysaccharide-specific responses and succumb to challenge with live type 3 serotype pneumococcus, indicating that TACI is required for T cell independent antibody responses to bacterial-associated polysaccharides. Although we have found that TACI is dispensable for controlling B. hermsii infection, mice deficient in BAFFR or BAFF exhibit impairment in B. hermsii-specific IgM responses and clearance of bacteremia. Collectively, these data indicate a disparity in the roles for TACI and BAFFR in primary T cell-independent antibody responses to bacterial pathogens. PMID- 24218483 TI - NLRP1 is an inflammasome sensor for Toxoplasma gondii. AB - The obligate intracellular parasite Toxoplasma gondii is able to infect nearly all nucleated cell types of warm-blooded animals. This is achieved through the injection of hundreds of parasite effectors into the host cell cytosol, allowing the parasite to establish a vacuolar niche for growth, replication, and persistence. Here we show that Toxoplasma infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign components leading to inflammation and cell death. Oral infection with Toxoplasma triggers an inflammasome response that is protective to the host, limiting parasite load and dissemination. Toxoplasma infection is sufficient to generate an inflammasome response in germfree animals. Interleukin 1beta (IL-1beta) secretion by macrophage requires the effector caspases 1 and 11, the adapter ASC, and NLRP1, the sensor previously described to initiate the inflammasome response to Bacillus anthracis lethal factor. The allele of NLRP1b derived from 129 mice is sufficient to enhance the B6 bone marrow-derived macrophage (BMDM) inflammasome response to Toxoplasma independent of the lethal factor proteolysis site. Moreover, N-terminal processing of NLRP1b, the only mechanism of activation known to date, is not observed in response to Toxoplasma infection. Cumulatively, these data indicate that NLRP1 is an innate immune sensor for Toxoplasma infection, activated via a novel mechanism that corresponds to a host-protective innate immune response to the parasite. PMID- 24218485 TI - Alternative data sources for estimating multiple sclerosis prevalence. PMID- 24218484 TI - Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. AB - Plasmodium falciparum causes malaria disease during the asexual blood stages of infection when merozoites invade erythrocytes and replicate. Merozoite surface proteins (MSPs) are proposed to play a role in the initial binding of merozoites to erythrocytes, but precise roles remain undefined. Based on electron microscopy studies of invading Plasmodium merozoites, it is proposed that the majority of MSPs are cleaved and shed from the surface during invasion, perhaps to release receptor-ligand interactions. In this study, we demonstrate that there is not universal cleavage of MSPs during invasion. Instead, there is sequential and coordinated cleavage and shedding of proteins, indicating a diversity of roles for surface proteins during and after invasion. While MSP1 and peripheral surface proteins such as MSP3, MSP7, serine repeat antigen 4 (SERA4), and SERA5 are cleaved and shed at the tight junction between the invading merozoite and erythrocyte, the glycosylphosphatidylinositol (GPI)-anchored proteins MSP2 and MSP4 are carried into the erythrocyte without detectable processing. Following invasion, MSP2 rapidly degrades within 10 min, whereas MSP4 is maintained for hours. This suggests that while some proteins that are shed upon invasion may have roles in initial contact steps, others function during invasion and are then rapidly degraded, whereas others are internalized for roles during intraerythrocytic development. Interestingly, anti-MSP2 antibodies did not inhibit invasion and instead were carried into erythrocytes and maintained for approximately 20 h without inhibiting parasite development. These findings provide new insights into the mechanisms of invasion and knowledge to advance the development of new drugs and vaccines against malaria. PMID- 24218486 TI - Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: yes. PMID- 24218487 TI - Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: no. PMID- 24218488 TI - Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: commentary. PMID- 24218489 TI - Response to letter from Dr KL Munger, 'childhood obesity is a risk factor for multiple sclerosis'. PMID- 24218490 TI - Unequal redundancy in maize knotted1 homeobox genes. AB - The knotted1 (kn1) homeobox (knox) gene family was first identified through gain of-function dominant mutants in maize (Zea mays). Class I knox members are expressed in meristems but excluded from leaves. In maize, a loss-of-function phenotype has only been characterized for kn1. To assess the function of another knox member, we characterized a loss-of-function mutation of rough sheath1 (rs1). rs1-mum1 has no phenotype alone but exacerbates several aspects of the kn1 phenotype. In permissive backgrounds in which kn1 mutants grow to maturity, loss of a single copy of rs1 enhances the tassel branch reduction phenotype, while loss of both copies results in limited shoots. In less introgressed lines, double mutants can grow to maturity but are shorter. Using a KNOX antibody, we demonstrate that RS1 binds in vivo to some of the KN1 target genes, which could partially explain why KN1 binds many genes but modulates few. Our results demonstrate an unequal redundancy between knox genes, with a role for rs1 only revealed in the complete absence of kn1. PMID- 24218491 TI - Genome-wide association mapping combined with reverse genetics identifies new effectors of low water potential-induced proline accumulation in Arabidopsis. AB - Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID- 24218492 TI - Regulation of compound leaf development by PHANTASTICA in Medicago truncatula. AB - Plant leaves, simple or compound, initiate as peg-like structures from the peripheral zone of the shoot apical meristem, which requires class I KNOTTED-LIKE HOMEOBOXI (KNOXI) transcription factors to maintain its activity. The MYB domain protein encoded by the ASYMMETRIC LEAVES1/ROUGH SHEATH2/PHANTASTICA (ARP) gene, together with other factors, excludes KNOXI gene expression from incipient leaf primordia to initiate leaves and specify leaf adaxial identity. However, the regulatory relationship between ARP and KNOXI is more complex in compound-leafed species. Here, we investigated the role of ARP and KNOXI genes in compound leaf development in Medicago truncatula. We show that the M. truncatula phantastica mutant exhibited severe compound leaf defects, including curling and deep serration of leaf margins, shortened petioles, increased rachises, petioles acquiring motor organ characteristics, and ectopic development of petiolules. On the other hand, the M. truncatula brevipedicellus mutant did not exhibit visible compound leaf defects. Our analyses show that the altered petiole development requires ectopic expression of ELONGATED PETIOLULE1, which encodes a lateral organ boundary domain protein, and that the distal margin serration requires the auxin efflux protein M. truncatula PIN-FORMED10 in the M. truncatula phantastica mutant. PMID- 24218493 TI - Recovering root system traits using image analysis exemplified by two-dimensional neutron radiography images of lupine. AB - Root system traits are important in view of current challenges such as sustainable crop production with reduced fertilizer input or in resource-limited environments. We present a novel approach for recovering root architectural parameters based on image-analysis techniques. It is based on a graph representation of the segmented and skeletonized image of the root system, where individual roots are tracked in a fully automated way. Using a dynamic root architecture model for deciding whether a specific path in the graph is likely to represent a root helps to distinguish root overlaps from branches and favors the analysis of root development over a sequence of images. After the root tracking step, global traits such as topological characteristics as well as root architectural parameters are computed. Analysis of neutron radiographic root system images of lupine (Lupinus albus) grown in mesocosms filled with sandy soil results in a set of root architectural parameters. They are used to simulate the dynamic development of the root system and to compute the corresponding root length densities in the mesocosm. The graph representation of the root system provides global information about connectivity inside the graph. The underlying root growth model helps to determine which path inside the graph is most likely for a given root. This facilitates the systematic investigation of root architectural traits, in particular with respect to the parameterization of dynamic root architecture models. PMID- 24218494 TI - Is cryoanalgesia effective for post-thoracotomy pain? AB - A best evidence topic was written according to a structured protocol. The question addressed was whether cryoanalgesia improves post-thoracotomy pain and recovery. Twelve articles were identified that provided the best evidence to answer the question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were pain scores, additional opiate requirements, incidence of hypoesthesia and change in lung function. Half of the articles reviewed failed to demonstrate superiority of cryoanalgesia over other pain relief methods; however, additional opiate requirements were reduced in patients receiving cryoanalgesia. Change in lung function postoperatively was equivocal. Cryoanalgesia potentiated the incidence of postoperative neuropathic pain. Further analysis of the source of cryoanalgesia, duration, temperature obtained and extent of blockade revealed numerous discrepancies. Three studies utilized CO2 as the source of cryoanalgesia and four used nitrous oxide, but at differing temperatures and duration. Five studies did not reveal the source of cyroanalgesia. The number of intercostal nerves anaesthetized in each study varied. Seven articles anaesthetized three intercostal nerves, three articles used five intercostal nerves, one article used four intercostal nerves and one used one intercostal nerve at the thoracotomy site. Thoracotomy closure and site of area of chest drain insertion may have a role in postoperative pain; but only one article explained method of closure, and two articles mentioned placement of chest drain through blocked dermatomes. No causal inferences can be made by the above results as they are not directly comparable due to confounding variables between studies. Currently, the evidence does not support the use of cryoanalgesia alone as an effective method for relieving post-thoracotomy pain. PMID- 24218495 TI - Efficacy of contrast-enhanced ultrasonography in detecting graft rupture sites after abdominal aortic aneurysm repair. AB - Non-anastomotic graft rupture is a rare but critical complication after abdominal aortic aneurysm (AAA) repair. Therefore, identifying the rupture sites is important to perform endovascular stent grafting. A 78-year old man who had undergone Y-grafting for infrarenal AAA before 17 years was referred to our hospital with the complaints of abdominal pain. Computed tomography revealed acute pancreatitis and an enlargement around the grafted abdominal aorta. Contrast-enhanced ultrasonography revealed an extravazation from the graft body 1.5 cm distal to the proximal anastomosis, and endovascular stent grafting was successfully performed. Contrast-enhanced ultrasonography might be useful in detecting the graft rupture. PMID- 24218496 TI - Elastofibroma dorsi management and outcomes: review of 16 cases. AB - OBJECTIVES: Elastofibroma dorsi (ED) is a rare, benign lesion arising from connective tissue, usually found at the inferior pole of the scapula. To date, only a few small series have been reported in the English literature and there are few data about the long-term outcomes after surgery. Our goal is to contribute a better understanding of this tumour and to determine the long-term outcomes after surgery. METHODS: Sixteen patients with a diagnosis of ED were identified from the unit's database. The clinical presentation, diagnosis, pathological evidences and long-term outcomes were evaluated. RESULTS: There were 11 females and 5 males with a mean age of 61.1 years (range 38-78 years). The tumour was located on the right in 5 (31.2%) patients, on the left in 6 (37.5%) patients and bilaterally in 5 (31.2%). Six patients had painful scapular swelling resulting in restriction of movement of the shoulder whereas 10 reported only painful scapular mass. All 16 patients underwent complete resections. The tumour size ranged from 3 to 15 cm. The mean hospital stay was 3.1 +/- 1.4 days with a morbidity of 18.75% (seroma observed in 3 patients). The mean follow-up was 58.4 +/- 29.5 months (range 11-92 months). In 2 patients (12.5%) a new occurrence on the contralateral side was observed at the follow-up. CONCLUSIONS: Elastofibroma dorsi is a rare, ill-defined, pseudotumoural lesion of the soft tissues. Surgical treatment can be proposed if the lesion is symptomatic. Furthermore, at the follow-up, the possibility of new occurrences on the contralateral side should be kept in mind. PMID- 24218497 TI - Right massive haemothorax as the presentation of blunt cardiac rupture: the pitfall of coexisting pericardial laceration. AB - A 74-year old female was transferred to our institution because of blunt chest trauma. Chest X-ray and computed tomography (CT) revealed right haemothorax and little pericardial effusion. She was taken to the operating theatre for emergent operation because of hypotension and massive bleeding from the right-sided chest tube. Cardiopulmonary resuscitation was started during surgical exploration. There were three 1-cm lacerations actively bleeding from the right atrium and inferior vena cava junction, which were repaired successfully. Furthermore, we identified a 10 cm laceration in the right-side pleuropericardium and a communication existing between the pericardial space and the right pleural space. PMID- 24218498 TI - Effects of selective and nonselective nonsteroidal anti-inflammatory drugs on antibiotic efficacy of experimental group A streptococcal myonecrosis. AB - BACKGROUND: Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to more severe group A streptococcal (GAS) infections, yet a beneficial role for NSAIDs has been demonstrated in other experimental bacterial infections. METHODS: Nonselective (ketorolac tromethamine, ibuprofen, indomethacin), COX-1-selective (SC-560), or COX-2-selective (SC-236) NSAIDs +/- antibiotics (penicillin, clindamycin) were given to mice challenged intramuscularly with M-type 3 GAS and disease course was followed for 14 days. RESULTS. All nonselective NSAIDs significantly accelerated mortality and reduced antibiotic efficacy; COX-selective NSAIDs had no significant effects. CONCLUSIONS: Use of nonselective NSAIDs, either alone or as adjuncts to antibiotic therapy, for GAS soft tissue infection may contribute to worse outcomes. PMID- 24218499 TI - Serum procalcitonin level, viral polymerase chain reaction analysis, and lower respiratory tract infection. PMID- 24218500 TI - Whole-genome sequencing demonstrates that fidaxomicin is superior to vancomycin for preventing reinfection and relapse of infection with Clostridium difficile. AB - Whole-genome sequencing was used to determine whether the reductions in recurrence of Clostridium difficile infection observed with fidaxomicin in pivotal phase 3 trials occurred by preventing relapse of the same infection, by preventing reinfection with a new strain, or by preventing both outcomes. Paired isolates of C. difficile were available from 93 of 199 participants with recurrences (28 were treated with fidaxomicin, and 65 were treated with vancomycin). Given C. difficile evolutionary rates, paired samples <=2 single nucleotide variants (SNVs) apart were considered relapses, paired samples >10 SNVs apart were considered reinfection, and those 3-10 SNVs apart (or without whole-genome sequences) were considered indeterminate in a competing risks survival analysis. Fidaxomicin reduced the risk of both relapse (competing risks hazard ratio [HR], 0.40 [95% confidence interval {CI}, .25-.66]; P = .0003) and reinfection (competing risks HR, 0.33 [95% CI, 0.11-1.01]; P = .05). PMID- 24218501 TI - Trends in early initiation of antiretroviral therapy and characteristics of persons with HIV initiating therapy in San Francisco, 2007-2011. AB - In 2010, the San Francisco Department of Public Health offered antiretroviral therapy (ART) to all its patients with human immunodeficiency virus (HIV) regardless of CD4 count. We assessed trends in time from diagnosis to ART initiation and factors associated with ART initiation among San Francisco residents living with HIV between 2007 and 2011. Time to ART initiation decreased among those diagnosed with higher CD4 count. ART initiation rate was significantly higher in recent years and lower among African Americans, men who have sex with men who also inject drugs, and persons aged >=50 years. We found a trend toward early treatment. However, racial and social disparities persist. PMID- 24218476 TI - International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. AB - Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145-176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee. PMID- 24218502 TI - Latency-associated protein Acr1 impairs dendritic cell maturation and functionality: a possible mechanism of immune evasion by Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis (M. tuberculosis) in latently infected individuals survives and thwarts the attempts of eradication by the immune system. During latency, Acr1 is predominantly expressed by the bacterium. However, whether M. tuberculosis exploits its Acr1 in impairing the host immunity remains widely unexplored. Hence, currently we have investigated the role of Acr1 in influencing the differentiation and function of dendritic cells (DCs), which play a cardinal role in innate and adaptive immunity. Therefore, for the first time, we have revealed a novel mechanism of mycobacterial Acr1 in inhibiting the maturation and differentiation of DCs by inducing tolerogenic phenotype by modulating the expression of PD-L1; Tim-3; indoleamine 2, 3-dioxygenase (IDO); and interleukin 10. Furthermore, Acr1 interferes in the differentiation of DCs by targeting STAT 6 and STAT-3 pathways. Continuous activation of STAT-3 inhibited the translocation of NF-kappaB in Acr1-treated DCs. Furthermore, Acr1 also augmented the induction of regulatory T cells. These DCs displayed decline in their antigen uptake capacity and reduced ability to help T cells. Interestingly, M. tuberculosis exhibited better survival in Acr1-treated DCs. Thus, this study provides a crucial insight into a strategy adopted by M. tuberculosis to survive in the host by impairing the function of DCs. PMID- 24218503 TI - Reply to Musher et al. PMID- 24218504 TI - Investigation of anti-middle East respiratory syndrome antibodies in blood donors and slaughterhouse workers in Jeddah and Makkah, Saudi Arabia, fall 2012. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel, potentially zoonotic human coronavirus (HCoV). We investigated MERS-CoV antibodies using a staged approach involving an immunofluorescence assay (IFA), a differential recombinant IFA, and a plaque-reduction serum neutralization assay. In 130 blood donors sampled during 2012 in Jeddah and 226 slaughterhouse workers sampled in October 2012 in Jeddah and Makkah, Saudi Arabia, 8 reactive sera were seen in IFA but were resolved to be specific for established HCoVs by discriminative testing. There is no evidence that MERS-CoV circulated widely in the study region in fall 2012, matching an apparent absence of exported disease during the 2012 Hajj. PMID- 24218505 TI - Advancing priority research on the Middle East respiratory syndrome coronavirus. PMID- 24218506 TI - An animal model of MERS produced by infection of rhesus macaques with MERS coronavirus. AB - In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. To date, 114 human cases of MERS-CoV have been reported, with 54 fatalities. Animal models for MERS-CoV infection of humans are needed to elucidate MERS pathogenesis and to develop vaccines and antivirals. In this study, we developed rhesus macaques as a model for MERS-CoV using intratracheal inoculation. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection. PMID- 24218507 TI - L-type bovine spongiform encephalopathy in genetically susceptible and resistant sheep: changes in prion strain or phenotypic plasticity of the disease-associated prion protein? AB - BACKGROUND: Sheep with prion protein (PrP) gene polymorphisms QQ171 and RQ171 were shown to be susceptible to the prion causing L-type bovine spongiform encephalopathy (L-BSE), although RQ171 sheep specifically propagated a distinctive prion molecular phenotype in their brains, characterized by a high molecular mass protease-resistant PrP fragment (HMM PrPres), distinct from L-BSE in QQ171 sheep. METHODS: The resulting infectious and biological properties of QQ171 and RQ171 ovine L-BSE prions were investigated in transgenic mice expressing either bovine or ovine PrP. RESULTS: In both mouse lines, ovine L-BSE transmitted similarly to cattle-derived L-BSE, with respect to survival periods, histopathology, and biochemical features of PrPres in the brain, as well as splenotropism, clearly differing from ovine classic BSE or from scrapie strain CH1641. Nevertheless and unexpectedly, HMM PrPres was found in the spleen of ovine PrP transgenic mice infected with L-BSE from RQ171 sheep at first passage, reminiscent, in lymphoid tissues only, of the distinct PrPres features found in RQ171 sheep brains. CONCLUSIONS: The L-BSE agent differs from both ovine classic BSE or CH1641 scrapie maintaining its specific strain properties after passage in sheep, although striking PrPres molecular changes could be found in RQ171 sheep and in the spleen of ovine PrP transgenic mice. PMID- 24218509 TI - Haemophilus influenzae resides in tonsils and uses immunoglobulin D binding as an evasion strategy. AB - Haemophilus influenzae (Hi) causes respiratory tract infections and is also considered to be a commensal, particularly in preschool children. Tonsils from patients (n = 617) undergoing tonsillectomy due to chronic infection or hypertrophy were examined. We found that 51% of tonsils were positive for Hi, and in 95% of cases analyzed in detail (n = 39) Hi resided intracellularly in the core tonsillar tissue. Patients harbored several intracellular unique strains and the majority were nontypeable Hi (NTHi). Interestingly, the isolated NTHi bound soluble immunoglobulin (Ig) D at the constant heavy chain domain 1 as revealed by recombinant IgD/IgG chimeras. NTHi also interacted with B lymphocytes via the IgD B-cell receptor, resulting in internalization of bacteria, T-cell-independent activation via Toll-like receptor 9, and differentiation into non-NTHi-specific IgM-producing cells. Taken together, IgD-binding NTHi leads to an unspecific immune response and may support the bacteria to circumvent the host defense. PMID- 24218508 TI - Pharmacological inhibition of type I interferon signaling protects mice against lethal sepsis. AB - Current research on new therapeutic strategies for sepsis uses different animal models, such as the lipopolysaccharide-induced endotoxemia model and the cecal ligation and puncture (CLP) peritonitis model. By using genetic and pharmacologic inhibition of the type I interferon (IFN) receptor (IFNAR1), we show that type I IFN signaling plays a detrimental role in these sepsis models. Mortality after CLP was reduced even when type I IFN responses were blocked after the onset of sepsis. Our findings reveal that type I IFNs play an important detrimental role during sepsis by negatively regulating neutrophil recruitment. Reduced neutrophil influx likely occurs via the induction of the CXC motif chemokine 1. Moreover, human white blood cells exposed to heat-killed Pseudomonas aeruginosa secrete IFN beta and stimulate type I IFN signaling. We provide data that support pharmacologic inhibition of type I IFN signaling as a novel therapeutic treatment in severe sepsis. PMID- 24218510 TI - Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. AB - PURPOSE: Personalizing intravenous busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict i.v. busulfan doses over a wide age spectrum (0.1-66 years) that accounts for differences in age and body size. EXPERIMENTAL DESIGN: A population pharmacokinetic model based on normal fat mass and maturation based on postmenstrual age was built from 12,380 busulfan concentration time points obtained after i.v. busulfan administration in 1,610 HCT recipients. Subsequently, simulation results of the initial dose necessary to achieve a target Css with this model were compared with pediatric-only models. RESULTS: A two-compartment model with first-order elimination best fit the data. The population busulfan clearance was 12.4 L/h for an adult male with 62 kg normal fat mass (equivalent to 70 kg total body weight). Busulfan clearance, scaled to body size-specifically normal fat mass, is predicted to be 95% of the adult clearance at 2.5 years postnatal age. With a target Css of 770 ng/mL, a higher proportion of initial doses achieved the therapeutic window with this age- and size--dependent model (72%) compared with dosing recommended by the U.S. Food and Drug Administration (57%) or the European Medicines Agency (70%). CONCLUSION: This is the first population pharmacokinetic model developed to predict initial i.v. busulfan doses and personalize to a target Css over a wide age spectrum, ranging from infants to adults. PMID- 24218511 TI - A collagen-remodeling gene signature regulated by TGF-beta signaling is associated with metastasis and poor survival in serous ovarian cancer. AB - PURPOSE: To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer. EXPERIMENTAL DESIGN: Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using quantitative PCR and in situ hybridization. Alterations in gene expression by TGF-beta1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively. RESULTS: We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, and VCAN) that is associated with poor overall survival (OS) in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGF-beta1 signaling and is enriched in metastases in comparison with primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration, invasion, and tumor progression in mice. CONCLUSION: Our findings suggest that collagen-remodeling genes regulated by TGF-beta1 signaling promote metastasis and contribute to poor OS in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biologic relevance and thus may be useful as a therapeutic target. PMID- 24218512 TI - Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti CD99 antibody. AB - PURPOSE: Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patients with distant metastases have a poor prognosis. Noninvasive imaging is the standard approach to identifying sites of metastatic disease. We sought to develop a CD99-targeted imaging agent for staging Ewing sarcoma and other CD99-expressing tumors. EXPERIMENTAL DESIGN: We identified a CD99 antibody with highly specific binding in vitro and labeled this antibody with (64)Cu. Mice with either subcutaneous Ewing sarcoma xenograft tumors or micrometastases were imaged with the (64)Cu-labeled anti-CD99 antibody and these results were compared with conventional MRI and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) imaging. RESULTS: (64)Cu-labeled anti-CD99 antibody demonstrated high avidity for the CD99-positive subcutaneous tumors, with a high tumor-to-background ratio, greater than that demonstrated with FDG-PET. Micrometastases, measuring 1 to 2 mm on MRI, were not detected with FDG-PET but were readily visualized with the (64)Cu-labeled anti-CD99 antibody. Probe biodistribution studies demonstrated high specificity of the probe for CD99 positive tumors. CONCLUSIONS: (64)Cu-labeled anti-CD99 antibody can detect subcutaneous Ewing sarcoma tumors and metastatic sites with high sensitivity, outperforming FDG-PET in preclinical studies. This targeted radiotracer may have important implications for the diagnosis, surveillance, and treatment of Ewing sarcoma. Similarly, it may impact the management of other CD99 positive tumors. PMID- 24218513 TI - Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase. AB - PURPOSE: To investigate targeting of indoleamine 2,3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In a clinical phase I study, we treated 15 HLA-A2-positive patients with stage III-IV NSCLC in disease stabilization after standard chemotherapy. Patients were treated with imiquimod ointment and subcutaneous vaccinations (100 MUg IDO5 peptide, sequence ALLEIASCL, formulated in 900 MUL Montanide). Primary endpoint was toxicity. Clinical benefit and immunity were assessed as secondary endpoints. RESULTS: No severe toxicity was observed. One patient developed a partial response (PR) after one year of vaccine treatment, whereas long-lasting stable disease (SD) >= 8.5 months was demonstrated in another six patients. The median overall survival (OS) was 25.9 months. Patients demonstrated significant improved OS (P = 0.03) when compared with the group of patients excluded because of HLA-A2 negativity. IDO-specific CD8(+) T-cell immunity was demonstrated by IFN-gamma Elispot and Tetramer staining. Fluorescence-activated cell sorting analyses demonstrated a significant reduction of the Treg population (P = 0.03) after the sixth vaccine (2.5 months) compared with pretreatment levels. Furthermore, expression of IDO was detected in nine of ten tumor biopsies by immunohistochemistry. High-performance liquid chromatography analyses of kynurenine/tryptophan (Kyn/Trp) ratio in sera were performed. In long-term analyses of two clinical responding patients, the ratio of Kyn/Trp remained stable. CONCLUSIONS: The vaccine was well tolerated with no severe toxicity occurring. A median OS of 25.9 months was demonstrated and long lasting PR+SD was seen in 47% of the patients. PMID- 24218514 TI - Tumor-reactive CD8+ T cells in metastatic gastrointestinal cancer refractory to chemotherapy. AB - PURPOSE: To evaluate whether patients with metastatic gastrointestinal adenocarcinomas refractory to chemotherapy harbor tumor-reactive cytotoxic T cells. EXPERIMENTAL DESIGN: Expansion of CD8(+) tumor-infiltrating lymphocytes (TIL) and cancer cell lines was attempted from gastrointestinal cancer metastases in 16 consecutive patients for the study of antitumor immune recognition. Retroviral transduction of genes encoding T-cell receptors (TCR) was used to define HLA-restriction elements and specific reactivity. RESULTS: TIL were expanded from metastases in all patients, and new tumor cell lines were generated in 5 patients. Autologous tumor recognition without cross-reactivity against allogeneic HLA-matched gastrointestinal tumors was found in CD8(+) TIL from 3 of these 5 patients. In a patient with gastric cancer liver metastases, the repertoire of CD8(+) TIL was dominated by cytolytic sister clones reactive to 2 out of 4 autologous cancer cell lines restricted by HLA-C*0701. From the same patient, a rare CD8(+) TIL clone with a distinct TCR recognized all four cancer cell lines restricted by HLA-B*4901. In a patient with bile duct cancer, two distinct antitumor cytolytic clones were isolated from a highly polyclonal CD8(+) TIL repertoire. TCRs isolated from these clones recognized epitopes restricted by HLA-A*0201. In a third patient, CD8(+) TIL reactivity was progressively lost against an autologous colon cancer cell line that displayed loss of HLA haplotype. CONCLUSIONS: This study provides a basis for the development of immunotherapy for patients with advanced gastrointestinal malignancies by first establishing the presence of naturally occurring tumor-reactive CD8(+) TIL at the molecular level. PMID- 24218515 TI - The activation of the WNT signaling pathway is a Hallmark in neurofibromatosis type 1 tumorigenesis. AB - PURPOSE: The hallmark of neurofibromatosis type 1 (NF1) is the onset of dermal or plexiform neurofibromas, mainly composed of Schwann cells. Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors (MPNST) that are resistant to therapies. EXPERIMENTAL DESIGN: The aim of this study was to identify an additional pathway in the NF1 tumorigenesis. We focused our work on Wnt signaling that is highly implicated in cancer, mainly in regulating the proliferation of cancer stem cells. We quantified mRNAs of 89 Wnt pathway genes in 57 NF1-associated tumors including dermal and plexiform neurofibromas and MPNSTs. Expression of two major stem cell marker genes and five major epithelial mesenchymal transition marker genes was also assessed. The expression of significantly deregulated Wnt genes was then studied in normal human Schwann cells, fibroblasts, endothelial cells, and mast cells and in seven MPNST cell lines. RESULTS: The expression of nine Wnt genes was significantly deregulated in plexiform neurofibromas in comparison with dermal neurofibromas. Twenty Wnt genes showed altered expression in MPNST biopsies and cell lines. Immunohistochemical studies confirmed the Wnt pathway activation in NF1-associated MPNSTs. We then confirmed that the knockdown of NF1 in Schwann cells but not in epithelial cells provoked the activation of Wnt pathway by functional transfection assays. Furthermore, we showed that the protein expression of active beta-catenin was increased in NF1-silenced cell lines. Wnt pathway activation was strongly associated to both cancer stem cell reservoir and Schwann-mesenchymal transition. CONCLUSION: We highlighted the implication of Wnt pathway in NF1-associated tumorigenesis. PMID- 24218516 TI - Prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of patients with squamous cell carcinoma of the oral cavity. AB - PURPOSE: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC. EXPERIMENTAL DESIGN: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days). RESULTS: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001). CONCLUSIONS: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions. PMID- 24218518 TI - Religious prosociality and morality across cultures: how social enforcement of religion shapes the effects of personal religiosity on prosocial and moral attitudes and behaviors. AB - The question of whether religiosity is linked to prosocial behavior is currently hotly debated in psychology. This research contributes to this debate by showing that the nature of individuals' religious orientations and their relationships to prosociality depend on their country's social enforcement of religiosity. Our analyses of data from more than 70 countries indicate that in countries with no social pressure to follow a religion, religious individuals are more likely to endorse an intrinsic religious orientation (Study 1), engage in charity work (Study 2), disapprove of lying in their own interests (Study 3), and are less likely to engage in fraudulent behaviors (Study 4) compared with non-religious individuals. Ironically, in secular contexts, religious individuals are also more likely to condemn certain moral choices than non-religious individuals (Study 2). These effects of religiosity substantially weaken (and ultimately disappear) with increasing national levels of social enforcement of religiosity. PMID- 24218519 TI - Notice: PSPB articles by authors with retracted articles at PSPB or other journals: Stapel, Smeesters, and Sanna. AB - Numerous articles by the social psychologists Diederick Stapel, Dirk Smeesters, and Lawrence Sanna have been retracted in several different journals. The present notice reports the results of an investigation into papers authored or coauthored by these individuals, and published in Personality and Social Psychology Bulletin, that have not been retracted. The status of these papers range from data confirmed as legitimate by coauthors to, in many cases, being unknown as to their legitimacy. Given the lack of information in the latter cases, there is insufficient basis to recommend retraction at this time. Researchers using the results of these papers in their own work are advised to take the information reported in this notice into account. PMID- 24218517 TI - PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17. AB - PURPOSE: Cetuximab improves survival in patients with K-ras wild-type advanced colorectal cancer. We examined the predictive and prognostic significance of additional biomarkers in this setting, in particular BRAF, PIK3CA, and PTEN. EXPERIMENTAL DESIGN: Available colorectal tumor samples were analyzed from the CO.17 study. BRAF mutations were identified in tumor-derived DNA by direct sequencing and PIK3CA mutations were identified using a high-resolution melting screen with confirmation by sequencing. PTEN expression by immunohistochemistry (IHC) was performed on tissue microarrays. For each biomarker, prognostic and predictive effects were examined using a Cox model with tests for treatment biomarker interaction. RESULTS: A total of 572 patients with pretreated colorectal cancer were randomly assigned to receive cetuximab or best supportive care (BSC). Of 401 patients assessed for BRAF status, 13 (3.2%) had mutations. Of 407 patients assessed for PIK3CA status, 61 (15%) had mutations. Of 205 patients assessed for PTEN, 148 (72%) were negative for IHC expression. None of BRAF, PIK3CA, or PTEN was prognostic for overall or progression-free survival in the BSC arm. None was predictive of benefit from cetuximab, either in the whole study population or the K-ras wild-type subset. In the K-ras wild-type subgroup, the overall survival adjusted HR according to BRAF mutation status was 1.39 (interaction P = 0.69), PIK3CA mutation status HR = 0.79 (interaction P = 0.63), and PTEN expression HR = 0.75 (interaction P = 0.61). CONCLUSIONS: In chemotherapy-refractory colorectal cancer, neither PIK3CA mutation status nor PTEN expression were prognostic, nor were they predictive of benefit from cetuximab. Evaluation of predictive significance of BRAF mutations requires a larger sample size. PMID- 24218520 TI - Short-term projection of cancer incidence in Japan using an age-period interaction model with spline smoothing. AB - OBJECTIVE: In Japan, population-based cancer incidence data are reported several years behind the latest year of cancer mortality data. To bridge this gap, we aimed to determine a short-term projection method for cancer incidence. METHODS: Data between 1985 and 2007 were obtained from the population-based cancer registries in four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Three projection models were examined: generalized linear model with age and period (A + P linear); generalized linear model with age, period and their interactions (A*P linear); and generalized additive model with age, period and their interactions smoothed by spline (A*P spline). We performed a 5-year projection for the years 2000 and 2005, based on the data of 1985-95 and 1985-2000, respectively. Seven cancer sites (stomach, liver, colorectal, lung, female breast, cervix uteri and prostate) and all cancers combined were analyzed. The accuracy of projection was evaluated by whether each observed number fell within the 95% confidence interval of the projected number. RESULTS: The A*P spline model accurately projected 8 of 13 cancer site-sex combinations, whereas the number of site-sex combinations of accurate projection was 2 and 6 for A + P linear and A*P linear models, respectively. For liver and colorectal cancers, the A*P spline model alone performed accurate projections; the relative differences between projected and observed numbers of cancer incidence ranged between -0.4 and +10.9% for the A*P spline, and between +7.4 and +37.6% for the other two models. All three models failed to project sudden increases in prostate cancer between 2000 and 2005. CONCLUSIONS: The A*P spline model is a candidate method for the projection of cancer incidence in Japan. However, we need a continuous validation for prostate cancer. PMID- 24218521 TI - Family history and BRCA1/BRCA2 status among Japanese ovarian cancer patients and occult cancer in a BRCA1 mutant case. AB - BACKGROUND: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. METHODS: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. RESULTS: Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. CONCLUSIONS: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations. PMID- 24218522 TI - Re: time to adjuvant chemotherapy for breast cancer in national comprehensive cancer network institutions. PMID- 24218523 TI - Response. PMID- 24218524 TI - Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation. AB - BACKGROUND: The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). METHODS: We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. RESULTS: A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. CONCLUSION: This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism. PMID- 24218525 TI - Temporal macrodynamics and microdynamics of the postoperative impedance at the tissue-electrode interface in deep brain stimulation patients. AB - OBJECTIVE: To study the temporal dynamics of tissue impedance after deep brain stimulation (DBS). BACKGROUND: DBS therapy commonly employs a constant voltage approach, and current delivery to the tissue is a function of electrode-tissue impedance. It is presumed that impedance fluctuates early postimplantation, with implications for variations in current delivery and therapeutic efficacy. We hypothesised that the largest variation will be recorded early after surgery, followed by stabilisation. METHODS: Review of impedance checks of implanted DBS systems at standard parameters during the first five months postimplantation. All measurement time points were binned into 1-week periods, and we used repeated measures analysis of variance with Tukey pairwise multiple comparisons correction. The analysis was repeated after normalising impedance values for each subject to that patient's baseline value. RESULTS: There was an initial (non significant) drop in impedance at week 1, followed by significant increase at week 3 (p=0.0002). There were no further significant differences in impedance values at subsequent time points. Analysis of normalised data showed a significant difference between the initial measurement in postoperative week 1 (normalised value 1) and week 3 (normalised value 1.73, p<0.0001), with no further difference among the subsequent weekly points during the 5-month follow up. No significant hourly variations were found at any time points. CONCLUSIONS: We found major changes in impedance within the first month postimplantation, with no further variation. This is an important confirmation in patients of this temporal dynamics of the impedance of implanted DBS hardware, with potential therapeutic implications. PMID- 24218526 TI - Comparison of activities of daily living impairments in Parkinson's disease patients as defined by the Pill Questionnaire and assessments by neurologists. AB - OBJECTIVES: To compare the clinical judgment of experienced neurologists after interviewing Parkinson's disease (PD) patients and their caregivers with the use of the Pill Questionnaire to determine the presence of impairments on activities of daily living (ADL). BACKGROUND: ADL impairment is a criterion for the diagnosis of dementia associated with PD. The Pill Questionnaire has been recommended as a screening tool to assess ADL impairment in PD patients, but its usefulness and validity have not been fully investigated. METHODS: We recruited idiopathic PD patients from 12 hospitals in Taiwan, and the patients underwent clinical assessments, a neuropsychological test battery and the Unified Parkinson Disease Rating Scale evaluation. The Pill Questionnaire was administered by study assistants. Patient and caregiver interviews were performed by experienced neurologists who were blinded to the Pill Questionnaire results. RESULTS: In total, 284 PD patients (mean age 71.8+/-9 years, mean education 8.7+/-5.3 years, mean disease duration 5.4+/-5.3 years) were recruited. 63 patients showed ADL impairment by the Pill Questionnaire, and 108 patients showed ADL impairment by neurologists' clinical interviews. kappa Statistics showed moderate agreement between the two methods (kappa=0.521, p<0.001). Of the 108 patients who were diagnosed with ADL impairment by neurologists, only 56 patients (51.9%) showed impairment according to the Pill Questionnaire. Most of the missed patients had milder cognitive impairment and lower motor disability. CONCLUSIONS: A comprehensive interview is essential to determine the presence of ADL impairment in PD patients, especially in patients with early PD. PMID- 24218527 TI - Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT. AB - OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo controlled phase of BENEFIT, patients were randomised to IFNB1b 250 MUg or placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years. RESULTS: Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. CONCLUSIONS: These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS. PMID- 24218529 TI - EMRs for specialists: physicians take the helm. PMID- 24218528 TI - Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial. AB - BACKGROUND: Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. METHODS: We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. FINDING: 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 ( 25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. INTERPRETATION: Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. REGISTRATION: Clinicaltrials.gov reference: NCT00767091. PMID- 24218530 TI - Omega-6 polyunsaturated fatty acids: is a broad cholesterol-lowering health claim appropriate? PMID- 24218532 TI - Stigma a major barrier to treatment for pregnant women with addictions. PMID- 24218531 TI - Diagnostic accuracy of level 3 portable sleep tests versus level 1 polysomnography for sleep-disordered breathing: a systematic review and meta analysis. AB - BACKGROUND: Greater awareness of sleep-disordered breathing and rising obesity rates have fueled demand for sleep studies. Sleep testing using level 3 portable devices may expedite diagnosis and reduce the costs associated with level 1 in laboratory polysomnography. We sought to assess the diagnostic accuracy of level 3 testing compared with level 1 testing and to identify the appropriate patient population for each test. METHODS: We conducted a systematic review and meta analysis of comparative studies of level 3 versus level 1 sleep tests in adults with suspected sleep-disordered breathing. We searched 3 research databases and grey literature sources for studies that reported on diagnostic accuracy parameters or disease management after diagnosis. Two reviewers screened the search results, selected potentially relevant studies and extracted data. We used a bivariate mixed-effects binary regression model to estimate summary diagnostic accuracy parameters. RESULTS: We included 59 studies involving a total of 5026 evaluable patients (mostly patients suspected of having obstructive sleep apnea). Of these, 19 studies were included in the meta-analysis. The estimated area under the receiver operating characteristics curve was high, ranging between 0.85 and 0.99 across different levels of disease severity. Summary sensitivity ranged between 0.79 and 0.97, and summary specificity ranged between 0.60 and 0.93 across different apnea-hypopnea cut-offs. We saw no significant difference in the clinical management parameters between patients who underwent either test to receive their diagnosis. INTERPRETATION: Level 3 portable devices showed good diagnostic performance compared with level 1 sleep tests in adult patients with a high pretest probability of moderate to severe obstructive sleep apnea and no unstable comorbidities. For patients suspected of having other types of sleep disordered breathing or sleep disorders not related to breathing, level 1 testing remains the reference standard. PMID- 24218533 TI - With a disease for every day, who will care for the orphans? PMID- 24218534 TI - Raising awareness of breast reconstruction options. PMID- 24218537 TI - Sudden-onset anisocoria in a patient with upper respiratory tract infection. PMID- 24218538 TI - A conversation with 2013 Gairdner Wightman Award winner Dr. James Hogg. PMID- 24218539 TI - Cut-and-paste clinical notes confuse care, say US internists. PMID- 24218541 TI - Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis. AB - A critical piece in the translation of preclinical studies to clinical trials is the determination of dosing regimens that allow maximum therapeutic benefit with minimum toxicity. The preclinical pharmacokinetic (PK)/pharmacodynamic (PD) profile of tofacitinib, an oral Janus kinase (JAK) inhibitor, in a mouse collagen induced arthritis (mCIA) model was compared with clinical PK/PD data from patients with rheumatoid arthritis (RA). Preclinical evaluations included target modulation and PK/PD modeling based on continuous subcutaneous infusion or oral once- or twice-daily (BID) dosing paradigms in mice. The human PK/PD profile was obtained from pooled data from four phase 2 studies in patients with RA, and maximal effect models were used to evaluate efficacy after 12 weeks of tofacitinib treatment (1-15 mg BID). In mCIA, the main driver of efficacy was inhibition of cytokine receptor signaling mediated by JAK1 heterodimers, but not JAK2 homodimers, and continuous daily inhibition was not required to maintain efficacy. Projected efficacy could be predicted from total daily exposure irrespective of the oral dosing paradigm, with a total steady-state plasma concentration achieving 50% of the maximal response (Cave50) of ~100 nM. Tofacitinib potency (ED50) in clinical studies was ~3.5 mg BID (90% confidence interval: 2.3, 5.5) or total Cave50 of ~40 nM, derived using Disease Activity Scores from patients with RA. The collective clinical and preclinical data indicated the importance of Cave as a driver of efficacy, rather than maximum or minimum plasma concentration (Cmax or Cmin), where Cave50 values were within ~2 fold of each other. PMID- 24218540 TI - Chemopreventive effects of an HDAC2-selective inhibitor on rat colon carcinogenesis and APCmin/+ mouse intestinal tumorigenesis. AB - Epigenetic modulators, particularly histone deacetylases (HDACs), are valid targets for cancer prevention and therapy. Recent studies report that HDAC2 overexpression is associated with colon tumor progression and is a potential target for colon cancer prevention. This study tested chemopreventive and dose response effects of Ohio State University HDAC42 (OSU-HDAC42), a selective HDAC2 inhibitor, using a rat colon carcinogenesis model to assess aberrant crypt foci inhibition and a familial adenomatous polyposis model to assess intestinal tumor inhibition. Colonic aberrant crypt foci were induced by azoxymethane (AOM) (15 mg/kg body weight, once-weekly subcutaneous injections at 8 and 9 weeks age). One week after AOM treatment, groups of rats were fed an AIN-76A diet containing 0, 75, 150, and 300 ppm OSU-HDAC42 for 8 weeks, and colonic aberrant crypt foci were evaluated. To assess the inhibitory effect of OSU-HDAC42 on small-intestinal polyps and colon tumor growth, 6-week-old male C57Bl/6J-APC(min/+)mice were fed an AIN-76A diet containing 150 ppm OSU-HADC42 or 300 ppm pan-HDAC inhibitor suberoylanilide hydroxyamic acid (SAHA) for 80 days. Our results demonstrate that dietary OSU-HDAC42 produced dose-dependent inhibition of AOM-induced colonic aberrant crypt foci formation (13-50%; P < 0.01 to < 0.0001) and reduced multiple crypts with >= 4 crypts per focus (25-57%; P < 0.01 to < 0.0001) in F344 rats. Our findings show that 150 ppm OSU-HDAC42 significantly inhibited small intestinal polyps (>46%; P < 0.001), with polyp size measuring >1 mm (P < 0.001), and colon tumors (>26%) in APC(min/+)mice, whereas 300 ppm SAHA showed nonsignificant inhibition. Mice fed 150 ppm OSU-HDAC42 had significantly decreased HDAC2, proliferating cell nuclear antigen, B cell lymphoma 2, cyclin dependent kinase 2, and cell division cycle homolog 25C expression levels and increased p53 expression levels. These observations demonstrate the chemopreventive efficacy of OSU-HDAC42 against chemically induced and polyposis models of intestinal tumorigenesis. PMID- 24218542 TI - CoIN: a network analysis for document triage. AB - In recent years, there was a rapid increase in the number of medical articles. The number of articles in PubMed has increased exponentially. Thus, the workload for biocurators has also increased exponentially. Under these circumstances, a system that can automatically determine in advance which article has a higher priority for curation can effectively reduce the workload of biocurators. Determining how to effectively find the articles required by biocurators has become an important task. In the triage task of BioCreative 2012, we proposed the Co-occurrence Interaction Nexus (CoIN) for learning and exploring relations in articles. We constructed a co-occurrence analysis system, which is applicable to PubMed articles and suitable for gene, chemical and disease queries. CoIN uses co occurrence features and their network centralities to assess the influence of curatable articles from the Comparative Toxicogenomics Database. The experimental results show that our network-based approach combined with co-occurrence features can effectively classify curatable and non-curatable articles. CoIN also allows biocurators to survey the ranking lists for specific queries without reviewing meaningless information. At BioCreative 2012, CoIN achieved a 0.778 mean average precision in the triage task, thus finishing in second place out of all participants. Database URL: http://ikmbio.csie.ncku.edu.tw/coin/home.php. PMID- 24218543 TI - Velocity storage mechanism in zebrafish larvae. AB - The optokinetic reflex (OKR) and the angular vestibulo-ocular reflex (aVOR) complement each other to stabilize images on the retina despite self- or world motion, a joint mechanism that is critical for effective vision. It is currently hypothesized that signals from both systems integrate, in a mathematical sense, in a network of neurons operating as a velocity storage mechanism (VSM). When exposed to a rotating visual surround, subjects display the OKR, slow following eye movements frequently interrupted by fast resetting eye movements. Subsequent to light-off during optokinetic stimulation, eye movements do not stop abruptly, but decay slowly, a phenomenon referred to as the optokinetic after-response (OKAR). The OKAR is most likely generated by the VSM. In this study, we observed the OKAR in developing larval zebrafish before the horizontal aVOR emerged. Our results suggest that the VSM develops prior to and without the need for a functional aVOR. It may be critical to ocular motor control in early development as it increases the efficiency of the OKR. PMID- 24218545 TI - A catalytic independent function of the deubiquitinating enzyme USP14 regulates hippocampal synaptic short-term plasticity and vesicle number. AB - The ubiquitin proteasome system is required for the rapid and precise control of protein abundance that is essential for synaptic function. USP14 is a proteasome bound deubiquitinating enzyme that recycles ubiquitin and regulates synaptic short-term synaptic plasticity. We previously reported that loss of USP14 in ax(J) mice causes a deficit in paired pulse facilitation (PPF) at hippocampal synapses. Here we report that USP14 regulates synaptic function through a novel, deubiquitination-independent mechanism. Although PPF is usually inversely related to release probability, USP14 deficiency impairs PPF without altering basal release probability. Instead, the loss of USP14 causes a large reduction in the number of synaptic vesicles. Over-expression of a catalytically inactive form of USP14 rescues the PPF deficit and restores synaptic vesicle number, indicating that USP14 regulates presynaptic structure and function independently of its role in deubiquitination. Finally, the PPF deficit caused by loss of USP14 can be rescued by pharmacological inhibition of proteasome activity, suggesting that inappropriate protein degradation underlies the PPF impairment. Overall, we demonstrate a novel, deubiquitination-independent function for USP14 in influencing synaptic architecture and plasticity. PMID- 24218544 TI - Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells. AB - The cerebellum plays crucial roles in controlling sensorimotor functions. The neural output from the cerebellar cortex is transmitted solely by Purkinje cells (PCs), whose impairment causes cerebellar ataxia. Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominant disease, and SCA13 patients exhibit cerebellar atrophy and cerebellar symptoms. Recent studies have shown that missense mutations in the voltage-gated K(+) channel Kv3.3 are responsible for SCA13. In the rodent brain, Kv3.3 mRNAs are expressed most strongly in PCs, suggesting that the mutations severely affect PCs in SCA13 patients. Nevertheless, how these mutations affect the function of Kv3.3 in PCs and, consequently, the morphology and neuronal excitability of PCs remains unclear. To address these questions, we used lentiviral vectors to express mutant mouse Kv3.3 (mKv3.3) channels harbouring an R424H missense mutation, which corresponds to the R423H mutation in the Kv3.3 channels of SCA13 patients, in mouse cerebellar cultures. The R424H mutant-expressing PCs showed decreased outward current density, broadened action potentials and elevated basal [Ca(2+)]i compared with PCs expressing wild-type mKv3.3 subunits or those expressing green fluorescent protein alone. Moreover, expression of R424H mutant subunits induced impaired dendrite development and cell death selectively in PCs, both of which were rescued by blocking P/Q-type Ca(2+) channels in the culture conditions. We therefore concluded that expression of R424H mutant subunits in PCs markedly affects the function of endogenous Kv3 channels, neuronal excitability and, eventually, basal [Ca(2+)]i, leading to cell death. These results suggest that PCs in SCA13 patients also exhibit similar defects in PC excitability and induced cell death, which may explain the pathology of SCA13. PMID- 24218546 TI - Functional properties of extrasynaptic AMPA and NMDA receptors during postnatal hippocampal neurogenesis. AB - In the mammalian hippocampus, new granule cells are continuously generated throughout life. Although it is well known that they rapidly form several thousand new glutamatergic synapses, the underlying mechanisms are not well understood. As extrasynaptic NMDA receptors are believed to support the generation of new spines, we have studied the functional properties of extrasynaptic ionotropic glutamate receptors in newborn granule cells in juvenile rats during and after synaptic integration. Using the fast application of glutamate to outside-out membrane patches, we show that all immature granule cells express functional AMPA and NMDA receptors. The density of AMPA receptors was small in cells starting to receive excitatory synaptic input (~30 pS MUm(-2)) but substantially increased during synaptic integration to finally reach ~120 pS MUm(-2) in fully mature cells. Interestingly, AMPA receptors showed a biphasic change in desensitization time constant which was slowest during synaptic integration and substantially faster before and afterwards. This was paralleled by a change in the non-desensitizing current component which was maximal during synaptic integration and about 50% smaller afterwards. Surprisingly, the NMDA receptor kinetics and density in young cells was already comparable to mature cells (~10 pS MUm(-2)), leading to an enhanced NMDA/AMPA receptor density ratio. Similar to somatic outside-out patches, iontophoretic application of glutamate onto dendrites also revealed an enhanced dendritic NMDA/AMPA ratio in young cells. These data indicate that prolonged AMPA receptor currents in newly generated young granule cells might support the effective activation of extrasynaptic NMDA receptors and therefore constitute a competitive advantage over mature cells for new synapse formation. PMID- 24218547 TI - Image-based assessment of microvascular function and structure in collagen XV- and XVIII-deficient mice. AB - Collagen XV and XVIII are ubiquitous constituents of basement membranes. We aimed to study the physiological roles of these two components of the permeability barrier non-invasively in striated muscle in mice deficient in collagen XV or XVIII by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Structural information was obtained with transmission electron microscopy (TEM). MR data were analysed by two different analysis methods to quantify tissue perfusion and microcirculatory exchange parameters to rule out data analysis method-dependent results. Control mice (C57BL/6J Ola/Hsd strain) or mice lacking either collagen XV (Col15a1(-/-)) or XVIII (Col18a1(-/-)) were included in the study. MR images were acquired using a preclinical system using gadodiamide (Gd DTPA-BMA, molecular weight 0.58 kDa) as a tracer. Exchange capacity (permeability (P)-surface area (S) product relative to blood flow (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB was significantly increased in Col18a1(-/-), but slightly decreased in Col15a1(-/-). PS was significantly increased only in Col18a1(-/-) even though P was increased in both phenotypes suggesting S might also be reduced in Col15a1(-/-) mice. Immunohistochemistry and electron microscopy demonstrated alterations in capillary density and morphology in both knockout mouse strains in comparison to the control mice. Both collagen XV and XVIII are important for maintaining normal capillary permeability in the striated muscle. DCE-MRI and the perfusion analyses successfully determined microvascular haemodynamic parameters of genetically modified mice and gave results consistent with more invasive methods. PMID- 24218548 TI - Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition. AB - Targeted therapeutics that block signal transduction through the RAS-RAF-MEK and PI3K-AKT-mTOR pathways offer significant promise for the treatment of human malignancies. Dual inhibition of MAP/ERK kinase (MEK) and phosphatidylinositol 3 kinase (PI3K) with the potent and selective small-molecule inhibitors GDC-0973 and GDC-0941 has been shown to trigger tumor cell death in preclinical models. Here we have used phosphomotif antibodies and mass spectrometry (MS) to investigate the effects of MEK/PI3K dual inhibition during the period immediately preceding cell death. Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damage-response (DDR) motif, as defined by a phosphorylated serine or threonine residue adjacent to glutamine, [s/t]Q. In total, >2,000 [s/t]Q phosphorylation sites on >850 proteins were identified by LC-MS/MS, including an extensive network of DDR proteins. Linear mixed-effects modeling revealed 101 proteins in which [s/t]Q phosphorylation was altered significantly in response to GDC 0973/GDC-0941. Among the most dramatic changes, we observed rapid and sustained phosphorylation of sites within the ABCDE cluster of DNA-dependent protein kinase. Preincubation of cells with the inhibitors of the DDR kinases DNA dependent protein kinase or ataxia-telangiectasia mutated enhanced GDC-0973/GDC 0941-mediated cell death. Network analysis revealed specific enrichment of proteins involved in RNA metabolism along with canonical DDR proteins and suggested a prominent role for this pathway in the response to MEK/PI3K dual inhibition. PMID- 24218549 TI - A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions. AB - The E3 transcription unit of human adenoviruses (Ads) encodes immunomodulatory proteins. Interestingly, the size and composition of the E3 region differs considerably among Ad species, suggesting that distinct sets of immunomodulatory E3 proteins may influence their interaction with the human host and the disease pattern. However, to date, only common immune evasion functions of species C E3 proteins have been described. Here we report on the immunomodulatory activity of a species D-specific E3 protein, E3/49K. Unlike all other E3 proteins that act on infected cells, E3/49K seems to target uninfected cells. Initially synthesized as an 80- to 100-kDa type I transmembrane protein, E3/49K is subsequently cleaved, with the large ectodomain (sec49K) secreted. We found that purified sec49K exhibits specific binding to lymphoid cell lines and all primary leukocytes, but not to fibroblasts or epithelial cells. Consistent with this binding profile and the molecular mass, the sec49K receptor was identified as the cell surface protein tyrosine phosphatase CD45. Antibody-blocking studies suggested that sec49K binds to the membrane proximal domains present in all CD45 isoforms. Functional studies showed that sec49K can suppress the activation and cytotoxicity of natural killer cells as well as the activation, signaling, and cytokine production of T cells. Thus, we have discovered an adenovirus protein that is actively secreted and describe immunomodulatory activities of an E3 protein uniquely expressed by a single Ad species. PMID- 24218550 TI - Persistence of hippocampal multivoxel patterns into postencoding rest is related to memory. AB - The transformation of new experiences into lasting memories is thought to be mediated by postencoding reactivation or the reexpression of activity patterns that characterize prior encoding experiences during subsequent offline periods. Although hippocampal reactivation has been well-described in the rodent, evidence for postencoding persistence of hippocampal encoding patterns has yet to be described in humans. Using functional MRI, we examined the persistence of multivoxel hippocampal encoding patterns into postencoding rest periods. To characterize activity patterns, we computed the pairwise multivoxel correlation structure (MVCS) across hippocampal voxels during two distinct encoding tasks as well as during pre- and postencoding rest periods. We found that the hippocampal MVCS for each encoding task was more similar to the MVCS during immediate postencoding rest periods compared with a preencoding, baseline rest period. Additionally, using a principal component decomposition approach, we found that the strongest encoding patterns showed evidence of preferential persistence into immediate postencoding rest periods. Finally, the extent to which the strongest encoding patterns showed evidence of preferential persistence into immediate postencoding rest significantly correlated with later memory for stimuli seen during encoding. Taken together, these results provide strong evidence for hippocampal reactivation in humans, which was measured by the persistence of hippocampal encoding patterns into immediate postencoding rest periods, and importantly, provide a possible link between this persistence and memory consolidation. PMID- 24218551 TI - ErbB4 reduces synaptic GABAA currents independent of its receptor tyrosine kinase activity. AB - ErbB4 signaling in the central nervous system is implicated in neuropsychiatric disorders and epilepsy. In cortical tissue, ErbB4 associates with excitatory synapses located on inhibitory interneurons. However, biochemical and histological data described herein demonstrate that the vast majority of ErbB4 is extrasynaptic and detergent-soluble. To explore the function of this receptor population, we used unbiased proteomics, in combination with electrophysiological, biochemical, and cell biological techniques, to identify a clinically relevant ErbB4-interacting protein, the GABAA receptor alpha1 subunit (GABAR alpha1). We show that ErbB4 and GABAR alpha1 are robustly coexpressed in hippocampal interneurons, and that ErbB4-null mice have diminished cortical GABAR alpha1 expression. Moreover, we characterize a Neuregulin-mediated ErbB4 signaling modality, independent of receptor tyrosine kinase activity, that couples ErbB4 to decreased postsynaptic GABAR currents on inhibitory interneurons. Consistent with an evolving understanding of GABAR trafficking, this pathway requires both clathrin-mediated endocytosis and protein kinase C to reduce GABAR inhibitory currents, surface GABAR alpha1 expression, and colocalization with the inhibitory postsynaptic protein gephyrin. Our results reveal a function of ErbB4, independent of its tyrosine kinase activity, that modulates postsynaptic inhibitory control of hippocampal interneurons and may provide a novel pharmacological target in the treatment of neuropsychiatric disorders and epilepsy. PMID- 24218552 TI - Quantifying the dynamic interactions between a clathrin-coated pit and cargo molecules. AB - Clathrin-mediated endocytosis takes place through the recruitment of cargo molecules into a growing clathrin-coated pit (CCP). Despite the importance of this process to all mammalian cells, little is yet known about the interaction dynamics between cargo and CCPs. These interactions are difficult to study because CCPs display a large degree of lifetime heterogeneity and the interactions with cargo molecules are time dependent. We use single-molecule total internal reflection fluorescence microscopy, in combination with automatic detection and tracking algorithms, to directly visualize the recruitment of individual voltage-gated potassium channels into forming CCPs in living cells. We observe association and dissociation of individual channels with a CCP and, occasionally, their internalization. Contrary to widespread ideas, cargo often escapes from a pit before abortive CCP termination or endocytic vesicle production. Thus, the binding times of cargo molecules associating to CCPs are much shorter than the overall endocytic process. By measuring tens of thousands of capturing events, we build the distribution of capture times and the times that cargo remains confined to a CCP. An analytical stochastic model is developed and compared with the measured distributions. Due to the dynamic nature of the pit, the model is non-Markovian and it displays long-tail power law statistics. The measured distributions and model predictions are in excellent agreement over more than five orders of magnitude. Our findings identify one source of the large heterogeneities in CCP dynamics and provide a mechanism for the anomalous diffusion of proteins in the plasma membrane. PMID- 24218553 TI - Structure and assembly of an inner membrane platform for initiation of type IV pilus biogenesis. AB - Type IV pili are long fibers that are assembled by polymerization of a major pilin protein in the periplasm of a wide range of bacteria and archaea. They play crucial roles in pathogenesis, DNA transformation, and motility, and are capable of rapid retraction, generating powerful motor forces. PilN and PilO are integral inner membrane proteins that are essential for type IV pilus formation. Here, we show that PilN and PilO from Thermus thermophilus can be isolated as a complex with PilM, a cytoplasmic protein with structural similarities to the cytoskeletal protein MreB. The crystal structure of the periplasmic portion of PilN forms a homodimer with an extensive, conserved interaction interface. We conducted serial 3D reconstructions by electron microscopy of PilMN, PilMNO, and PilMNO bound to the major pilin protein PilA4, to chart the assembly of the inner membrane pilus biogenesis platform. PilN drives the dimerization of the PilMN complex with a stoichiometry of 2:2; binding of two PilO monomers then causes the PilN periplasmic domains to dissociate. Finally, two PilA4 monomers bind to the periplasmic domains of PilN and PilO, to generate a T-shaped complex that is primed for addition of the pilin to the nascent pilus fiber. Docking of structures for PilM, PilN, PilO, and PilA4 into the electron density maps of the transmembrane complexes was used to generate a sequence of molecular structures that chart the initial events in type IV pilus formation, and provide structural information on the early events in this important secretion process. PMID- 24218554 TI - Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species. AB - Mitochondrial DNA (mtDNA) in adult human heart is characterized by complex molecular forms held together by junctional molecules of unknown biological significance. These junctions are not present in mouse hearts and emerge in humans during postnatal development, concomitant with increased demand for oxidative metabolism. To analyze the role of mtDNA organization during oxidative stress in cardiomyocytes, we used a mouse model, which recapitulates the complex mtDNA organization of human hearts by overexpression of the mitochondrial helicase, TWINKLE. Overexpression of TWINKLE rescued the oxidative damage induced replication stalling of mtDNA, reduced mtDNA point mutation load, and modified mtDNA rearrangements in heterozygous mitochondrial superoxide dismutase knockout hearts, as well as ameliorated cardiomyopathy in mice superoxide dismutase knockout in a p21-dependent manner. We conclude that mtDNA integrity influences cell survival and reason that tissue specific modes of mtDNA maintenance represent an adaptation to oxidative stress. PMID- 24218555 TI - Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration. AB - The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo. PMID- 24218556 TI - Human health impacts of ecosystem alteration. AB - Human activity is rapidly transforming most of Earth's natural systems. How this transformation is impacting human health, whose health is at greatest risk, and the magnitude of the associated disease burden are relatively new subjects within the field of environmental health. We discuss what is known about the human health implications of changes in the structure and function of natural systems and propose that these changes are affecting human health in a variety of important ways. We identify several gaps and limitations in the research that has been done to date and propose a more systematic and comprehensive approach to applied research in this field. Such efforts could lead to a more robust understanding of the human health impacts of accelerating environmental change and inform decision making in the land-use planning, environmental conservation, and public health policy realms. PMID- 24218557 TI - Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain. AB - DEAD-box proteins are involved in all aspects of RNA processing. They bind RNA in an ATP-dependent manner and couple ATP hydrolysis to structural and compositional rearrangements of ribonucleoprotein particles. Conformational control is a major point of regulation for DEAD-box proteins to act on appropriate substrates and in a timely manner in vivo. Binding partners containing a middle domain of translation initiation factor 4G (MIF4G) are emerging as important regulators. Well-known examples are eIF4G and Gle1, which bind and activate the DEAD-box proteins eIF4A and Dbp5. Here, we report the mechanism of an inhibiting MIF4G domain. We determined the 2.0-A resolution structure of the complex of human eIF4AIII and the MIF4G domain of the splicing factor Complexed With Cef1 (CWC22), an essential prerequisite for exon junction complex assembly by the splicing machinery. The CWC22 MIF4G domain binds both RecA domains of eIF4AIII. The mode of RecA2 recognition is similar to that observed in the activating complexes, yet is specific for eIF4AIII. The way the CWC22 MIF4G domain latches on the eIF4AIII RecA1 domain is markedly different from activating complexes. In the CWC22 eIF4AIII complex, the RNA-binding and ATP-binding motifs of the two RecA domains do not face each other, as would be required in the active state, but are in diametrically opposite positions. The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins. PMID- 24218558 TI - Metabolically programmed quality control system for dolichol-linked oligosaccharides. AB - The glycolipid Glc3Man9GlcNAc2-pyrophosphate-dolichol serves as the precursor for asparagine (N)-linked protein glycosylation in mammals. The biosynthesis of dolichol-linked oligosaccharides (DLOs) is arrested in low-glucose environments via unknown mechanisms, resulting in abnormal N-glycosylation. Here, we show that under glucose deprivation, DLOs are prematurely degraded during the early stages of DLO biosynthesis by pyrophosphatase, leading to the release of singly phosphorylated oligosaccharides into the cytosol. We identified that the level of GDP-mannose (Man), which serves as a donor substrate for DLO biosynthesis, is substantially reduced under glucose deprivation. We provide evidence that the selective shutdown of the GDP-Man biosynthetic pathway is sufficient to induce the release of phosphorylated oligosaccharides. These results indicate that glucose-regulated metabolic changes in the GDP-Man biosynthetic pathway cause the biosynthetic arrest of DLOs and facilitate their premature degradation by pyrophosphatase. We propose that this degradation system may avoid abnormal N glycosylation with premature oligosaccharides under conditions that impair efficient DLO biosynthesis. PMID- 24218559 TI - QnAs with Daniel Schacter. PMID- 24218560 TI - Phage T7 Gp2 inhibition of Escherichia coli RNA polymerase involves misappropriation of sigma70 domain 1.1. AB - Bacteriophage T7 encodes an essential inhibitor of the Escherichia coli host RNA polymerase (RNAP), the product of gene 2 (Gp2). We determined a series of X-ray crystal structures of E. coli RNAP holoenzyme with or without Gp2. The results define the structure and location of the RNAP sigma(70) subunit domain 1.1(sigma(1.1)(70)) inside the RNAP active site channel, where it must be displaced by the DNA upon formation of the open promoter complex. The structures and associated data, combined with previous results, allow for a complete delineation of the mechanism for Gp2 inhibition of E. coli RNAP. In the primary inhibition mechanism, Gp2 forms a protein-protein interaction with sigma(1.1)(70), preventing the normal egress of sigma(1.1)(70) from the RNAP active site channel. Gp2 thus misappropriates a domain of the RNAP holoenzyme, sigma(1.1)(70), to inhibit the function of the enzyme. PMID- 24218561 TI - Identifying external influences on global precipitation. AB - Changes in global (ocean and land) precipitation are among the most important and least well-understood consequences of climate change. Increasing greenhouse gas concentrations are thought to affect the zonal-mean distribution of precipitation through two basic mechanisms. First, increasing temperatures will lead to an intensification of the hydrological cycle ("thermodynamic" changes). Second, changes in atmospheric circulation patterns will lead to poleward displacement of the storm tracks and subtropical dry zones and to a widening of the tropical belt ("dynamic" changes). We demonstrate that both these changes are occurring simultaneously in global precipitation, that this behavior cannot be explained by internal variability alone, and that external influences are responsible for the observed precipitation changes. Whereas existing model experiments are not of sufficient length to differentiate between natural and anthropogenic forcing terms at the 95% confidence level, we present evidence that the observed trends result from human activities. PMID- 24218562 TI - Structural insights into the histone H1-nucleosome complex. AB - Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its alpha3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1-nucleosome complex. Our results lead to a residue specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID- 24218563 TI - TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection. AB - Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2 deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2(-/-) Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2(-/-) mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer-hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite. PMID- 24218564 TI - Phosphorylation-dependent derepression by the response regulator HnoC in the Shewanella oneidensis nitric oxide signaling network. AB - Nitric oxide (NO) is an important signaling molecule that regulates diverse physiological processes in all domains of life. In many gammaproteobacteria, NO controls behavioral responses through a complex signaling network involving heme nitric oxide/oxygen binding (H-NOX) domains as selective NO sensors. In Shewanella oneidensis, H-NOX-mediated NO sensing increases biofilm formation, which is thought to serve as a protective mechanism against NO cytotoxicity. The H-NOX/NO-responsive (hno) signaling network involves H-NOX-dependent control of HnoK autophosphorylation and phosphotransfer from HnoK to three response regulators. Two of these response regulators, HnoB and HnoD, regulate cyclic-di GMP levels and influence biofilm formation. However, the role of the third response regulator in the signaling network, HnoC, has not been determined. Here we describe a role for HnoC as a transcriptional repressor for the signaling genes in the hno network. The genes controlled by HnoC were identified by microarray analysis, and its function as a repressor was confirmed in vivo. HnoC belongs to an uncharacterized family of DNA-binding response regulators. Binding of HnoC to its promoter targets was characterized in vitro, revealing an unprecedented regulation mechanism, which further extends the functional capabilities of DNA-binding response regulators. In the unphosphorylated state HnoC forms a tetramer, which tightly binds to an inverted-repeat target sequence overlapping with the promoter regions. Phosphorylation of HnoC induces dissociation of the response regulator tetramer and detachment of subunits from the promoter DNA, which subsequently leads to transcriptional derepression. PMID- 24218565 TI - Deep ocean communities impacted by changing climate over 24 y in the abyssal northeast Pacific Ocean. AB - The deep ocean, covering a vast expanse of the globe, relies almost exclusively on a food supply originating from primary production in surface waters. With well documented warming of oceanic surface waters and conflicting reports of increasing and decreasing primary production trends, questions persist about how such changes impact deep ocean communities. A 24-y time-series study of sinking particulate organic carbon (food) supply and its utilization by the benthic community was conducted in the abyssal northeast Pacific (~4,000-m depth). Here we show that previous findings of food deficits are now punctuated by large episodic surpluses of particulate organic carbon reaching the sea floor, which meet utilization. Changing surface ocean conditions are translated to the deep ocean, where decadal peaks in supply, remineralization, and sequestration of organic carbon have broad implications for global carbon budget projections. PMID- 24218566 TI - Emergence of spatial structure in the tumor microenvironment due to the Warburg effect. AB - Drastic metabolic alterations, such as the Warburg effect, are found in most if not all types of malignant tumors. Emerging evidence shows that cancer cells benefit from these alterations, but little is known about how they affect noncancerous stromal cells within the tumor microenvironment. Here we show that cancer cells are better adapted to metabolic changes in the microenvironment, leading to the emergence of spatial structure. A clear example of tumor spatial structure is the localization of tumor-associated macrophages (TAMs), one of the most common stromal cell types found in tumors. TAMs are enriched in well perfused areas, such as perivascular and cortical regions, where they are known to potentiate tumor growth and invasion. However, the mechanisms of TAM localization are not completely understood. Computational modeling predicts that gradients--of nutrients, gases, and metabolic by-products such as lactate--emerge due to altered cell metabolism within poorly perfused tumors, creating ischemic regions of the tumor microenvironment where TAMs struggle to survive. We tested our modeling prediction in a coculture system that mimics the tumor microenvironment. Using this experimental approach, we showed that a combination of metabolite gradients and differential sensitivity to lactic acid is sufficient for the emergence of macrophage localization patterns in vitro. This suggests that cancer metabolic changes create a microenvironment where tumor cells thrive over other cells. Understanding differences in tumor-stroma sensitivity to these alterations may open therapeutic avenues against cancer. PMID- 24218567 TI - Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation. AB - Liver kinase b1 (Lkb1) protein kinase activity regulates cell growth and cell polarity. Here, we show Lkb1 is essential for maintaining a balance between mitotic and postmitotic cell fates in development of the mammalian skeleton. In this process, Lkb1 activity controls the progression of mitotic chondrocytes to a mature, postmitotic hypertrophic fate. Loss of this Lkb1-dependent switch leads to a dramatic expansion of immature chondrocytes and formation of enchondroma like tumors. Pathway analysis points to a mammalian target of rapamycin complex 1 dependent mechanism that can be partially suppressed by rapamycin treatment. These findings highlight a critical requirement for integration of mammalian target of rapamycin activity into developmental decision-making during mammalian skeletogenesis. PMID- 24218568 TI - Genetic variants related to gap junctions and hormone secretion influence conception rates in cows. AB - The recent decline in fertility is a serious problem in the dairy industry. To overcome this problem, we performed a genome-wide association study using 384 Holsteins and identified four loci associated with conception rates. Two of them contained gap junction-related genes: PKP2 and CTTNBP2NL. Further analysis confirmed that PKP2 increased connexin 43, a gap junction protein, whereas CTTNBP2NL dephosphorylated connexin 43. Knockdown of PKP2 or overexpression of CTTNBP2NL inhibited embryo implantation in mice. The other two loci contained neuroendocrine-related genes: SETD6 and CACNB2. Additional experiments indicated that SETD6 is involved in the transcriptional regulation of gonadotropin releasing hormone, whereas CACNB2 controlled the secretion of follicle stimulating hormone in cattle. The total allele substitution effect of these genes on conception rate was 3.5%. Our findings reveal important roles for gap junction communication and the neuroendocrine system in conception and suggest unique selection methods to improve reproductive performance in the livestock industry. PMID- 24218569 TI - Microphysical effects determine macrophysical response for aerosol impacts on deep convective clouds. AB - Deep convective clouds (DCCs) play a crucial role in the general circulation, energy, and hydrological cycle of our climate system. Aerosol particles can influence DCCs by altering cloud properties, precipitation regimes, and radiation balance. Previous studies reported both invigoration and suppression of DCCs by aerosols, but few were concerned with the whole life cycle of DCC. By conducting multiple monthlong cloud-resolving simulations with spectral-bin cloud microphysics that capture the observed macrophysical and microphysical properties of summer convective clouds and precipitation in the tropics and midlatitudes, this study provides a comprehensive view of how aerosols affect cloud cover, cloud top height, and radiative forcing. We found that although the widely accepted theory of DCC invigoration due to aerosol's thermodynamic effect (additional latent heat release from freezing of greater amount of cloud water) may work during the growing stage, it is microphysical effect influenced by aerosols that drives the dramatic increase in cloud cover, cloud top height, and cloud thickness at the mature and dissipation stages by inducing larger amounts of smaller but longer-lasting ice particles in the stratiform/anvils of DCCs, even when thermodynamic invigoration of convection is absent. The thermodynamic invigoration effect contributes up to ~27% of total increase in cloud cover. The overall aerosol indirect effect is an atmospheric radiative warming (3-5 W m(-2)) and a surface cooling (-5 to -8 W m(-2)). The modeling findings are confirmed by the analyses of ample measurements made at three sites of distinctly different environments. PMID- 24218570 TI - Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate. AB - The assembly of the three neuronal soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins synaptobrevin 2, syntaxin-1A, and SNAP-25 is the key step that leads to exocytotic fusion of synaptic vesicles. In the fully assembled SNARE complex, these three proteins form a coiled-coil four-helix bundle structure by interaction of their respective SNARE motifs. Although biochemical and mutational analyses strongly suggest that the heptad repeat SNARE motifs zipper into the final structure, little is known about the prefusion state of individual membrane-bound SNAREs and how they change conformation from the unzippered prefusion to the zippered postfusion state in a membrane environment. We have solved the solution NMR structure of micelle-bound syntaxin-1A in its prefusion conformation. In addition to the transmembrane helix, the SNARE motif consists of two well-ordered, membrane-bound helices separated by the "0-layer" residue Gln226. This unexpected structural order of the N- and C-terminal halves of the uncomplexed SNARE motif suggests the formation of partially zippered SNARE complex intermediates, with the 0-layer serving as a proofreading site for correct SNARE assembly. Interferometric fluorescence measurements in lipid bilayers confirm that the open SNARE motif helices of syntaxin interact with lipid bilayers and that association with the other target-membrane SNARE SNAP-25 lifts the SNARE motif off the membrane as a critical prerequisite for SNARE complex assembly and membrane fusion. PMID- 24218571 TI - Serotonin regulates glucose-stimulated insulin secretion from pancreatic beta cells during pregnancy. AB - In preparation for the metabolic demands of pregnancy, beta cells in the maternal pancreatic islets increase both in number and in glucose-stimulated insulin secretion (GSIS) per cell. Mechanisms have been proposed for the increased beta cell mass, but not for the increased GSIS. Because serotonin production increases dramatically during pregnancy, we tested whether flux through the ionotropic 5 HT3 receptor (Htr3) affects GSIS during pregnancy. Pregnant Htr3a(-/-) mice exhibited impaired glucose tolerance despite normally increased beta cell mass, and their islets lacked the increase in GSIS seen in islets from pregnant wild type mice. Electrophysiological studies showed that activation of Htr3 decreased the resting membrane potential in beta cells, which increased Ca(2+) uptake and insulin exocytosis in response to glucose. Thus, our data indicate that serotonin, acting in a paracrine/autocrine manner through Htr3, lowers the beta cell threshold for glucose and plays an essential role in the increased GSIS of pregnancy. PMID- 24218572 TI - CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome. AB - Cyclin-dependent kinases (CDKs) regulate a variety of fundamental cellular processes. CDK10 stands out as one of the last orphan CDKs for which no activating cyclin has been identified and no kinase activity revealed. Previous work has shown that CDK10 silencing increases ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2)-driven activation of the MAPK pathway, which confers tamoxifen resistance to breast cancer cells. The precise mechanisms by which CDK10 modulates ETS2 activity, and more generally the functions of CDK10, remain elusive. Here we demonstrate that CDK10 is a cyclin-dependent kinase by identifying cyclin M as an activating cyclin. Cyclin M, an orphan cyclin, is the product of FAM58A, whose mutations cause STAR syndrome, a human developmental anomaly whose features include toe syndactyly, telecanthus, and anogenital and renal malformations. We show that STAR syndrome-associated cyclin M mutants are unable to interact with CDK10. Cyclin M silencing phenocopies CDK10 silencing in increasing c-Raf and in conferring tamoxifen resistance to breast cancer cells. CDK10/cyclin M phosphorylates ETS2 in vitro, and in cells it positively controls ETS2 degradation by the proteasome. ETS2 protein levels are increased in cells derived from a STAR patient, and this increase is attributable to decreased cyclin M levels. Altogether, our results reveal an additional regulatory mechanism for ETS2, which plays key roles in cancer and development. They also shed light on the molecular mechanisms underlying STAR syndrome. PMID- 24218573 TI - Exploring network scaling through variations on optimal channel networks. AB - Metabolic allometry, a common pattern in nature, is a close to 3/4-power scaling law between metabolic rate and body mass in organisms, across and within species. An analogous relationship between metabolic rate and water volume in river networks has also been observed. Optimal channel networks (OCNs), at local optima, accurately model many scaling properties of river systems, including metabolic allometry. OCNs are embedded in 2D space; this work extends the model to three dimensions. In this paper we compare characteristics of 3D OCNs with 2D OCNs and with organic metabolic networks, studying the scaling behaviors of area, length, volume, and energy. We find that the 3D OCN has predictable characteristics analogous to those of the 2D version, as well as scaling properties similar to metabolic networks in biological organisms. PMID- 24218574 TI - Dynamic faces speed up the onset of auditory cortical spiking responses during vocal detection. AB - How low-level sensory areas help mediate the detection and discrimination advantages of integrating faces and voices is the subject of intense debate. To gain insights, we investigated the role of the auditory cortex in face/voice integration in macaque monkeys performing a vocal-detection task. Behaviorally, subjects were slower to detect vocalizations as the signal-to-noise ratio decreased, but seeing mouth movements associated with vocalizations sped up detection. Paralleling this behavioral relationship, as the signal to noise ratio decreased, the onset of spiking responses were delayed and magnitudes were decreased. However, when mouth motion accompanied the vocalization, these responses were uniformly faster. Conversely, and at odds with previous assumptions regarding the neural basis of face/voice integration, changes in the magnitude of neural responses were not related consistently to audiovisual behavior. Taken together, our data reveal that facilitation of spike latency is a means by which the auditory cortex partially mediates the reaction time benefits of combining faces and voices. PMID- 24218575 TI - QnAs with John Clarke. PMID- 24218576 TI - Transmission of multiple system atrophy prions to transgenic mice. AB - Prions are proteins that adopt alternative conformations, which become self propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson's disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83(+/+) mice homozygous for a mutant A53T alpha-synuclein transgene begin developing CNS dysfunction spontaneously at ~10 mo of age, uninoculated TgM83(+/-) mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain alpha-synuclein prions, we inoculated the TgM83(+/-) mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83(+/-) mice developed progressive signs of neurologic disease with an incubation period of ~100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83(+/+) mice developed neurologic dysfunction in ~210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated alpha-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that alpha-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago. PMID- 24218577 TI - Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH. AB - Using a systematic, whole-genome analysis of enhancer activity of human-specific endogenous retroviral inserts (hsERVs), we identified an element, hsERVPRODH, that acts as a tissue-specific enhancer for the PRODH gene, which is required for proper CNS functioning. PRODH is one of the candidate genes for susceptibility to schizophrenia and other neurological disorders. It codes for a proline dehydrogenase enzyme, which catalyses the first step of proline catabolism and most likely is involved in neuromediator synthesis in the CNS. We investigated the mechanisms that regulate hsERVPRODH enhancer activity. We showed that the hsERVPRODH enhancer and the internal CpG island of PRODH synergistically activate its promoter. The enhancer activity of hsERVPRODH is regulated by methylation, and in an undermethylated state it can up-regulate PRODH expression in the hippocampus. The mechanism of hsERVPRODH enhancer activity involves the binding of the transcription factor SOX2, whch is preferentially expressed in hippocampus. We propose that the interaction of hsERVPRODH and PRODH may have contributed to human CNS evolution. PMID- 24218578 TI - Bioavailable copper modulates oxidative phosphorylation and growth of tumors. AB - Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. PMID- 24218579 TI - FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner. AB - In Escherichia coli, complete unlinking of newly replicated sister chromosomes is required to ensure their proper segregation at cell division. Whereas replication links are removed primarily by topoisomerase IV, XerC/XerD-dif site-specific recombination can mediate sister chromosome unlinking in Topoisomerase IV deficient cells. This reaction is activated at the division septum by the DNA translocase FtsK, which coordinates the last stages of chromosome segregation with cell division. It has been proposed that, after being activated by FtsK, XerC/XerD-dif recombination removes DNA links in a stepwise manner. Here, we provide a mathematically rigorous characterization of this topological mechanism of DNA unlinking. We show that stepwise unlinking is the only possible pathway that strictly reduces the complexity of the substrates at each step. Finally, we propose a topological mechanism for this unlinking reaction. PMID- 24218580 TI - Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses. AB - Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1, in mice protects them from an ordinarily lethal dose of rickettsiae. Inhibition of Epac1 suppresses bacterial adhesion and invasion. Most importantly, pharmacological inhibition of Epac1 in vivo using an Epac-specific small-molecule inhibitor, ESI-09, completely recapitulates the Epac1 knockout phenotype. ESI-09 treatment dramatically decreases the morbidity and mortality associated with fatal spotted fever rickettsiosis. Our results demonstrate that Epac1-mediated signaling represents a mechanism for host pathogen interactions and that Epac1 is a potential target for the prevention and treatment of fatal rickettsioses. PMID- 24218581 TI - Revised standards for statistical evidence. AB - Recent advances in Bayesian hypothesis testing have led to the development of uniformly most powerful Bayesian tests, which represent an objective, default class of Bayesian hypothesis tests that have the same rejection regions as classical significance tests. Based on the correspondence between these two classes of tests, it is possible to equate the size of classical hypothesis tests with evidence thresholds in Bayesian tests, and to equate P values with Bayes factors. An examination of these connections suggest that recent concerns over the lack of reproducibility of scientific studies can be attributed largely to the conduct of significance tests at unjustifiably high levels of significance. To correct this problem, evidence thresholds required for the declaration of a significant finding should be increased to 25-50:1, and to 100-200:1 for the declaration of a highly significant finding. In terms of classical hypothesis tests, these evidence standards mandate the conduct of tests at the 0.005 or 0.001 level of significance. PMID- 24218582 TI - Gene amplification and microsatellite polymorphism underlie a recent insect host shift. AB - Host plant shifts of herbivorous insects may be a first step toward sympatric speciation and can create new pests of agriculturally important crops; however, the molecular mechanisms that mediate this process are poorly understood. Certain races of the polyphagous aphid Myzus persicae have recently adapted to feed on tobacco (Myzus persicae nicotianae) and show a reduced sensitivity to the plant alkaloid nicotine and cross-resistance to neonicotinoids a class of synthetic insecticides widely used for control. Here we show constitutive overexpression of a cytochrome P450 (CYP6CY3) allows tobacco-adapted races of M. persicae to efficiently detoxify nicotine and has preadapted them to resist neonicotinoid insecticides. CYP6CY3, is highly overexpressed in M. persicae nicotianae clones from three continents compared with M. persicae s.s. and expression level is significantly correlated with tolerance to nicotine. CYP6CY3 is highly efficient (compared with the primary human nicotine-metabolizing P450) at metabolizing nicotine and neonicotinoids to less toxic metabolites in vitro and generation of transgenic Drosophila expressing CYP6CY3 demonstrate that it confers resistance to both compounds in vivo. Overexpression of CYP6CY3 results from the expansion of a dinucleotide microsatellite in the promoter region and a recent gene amplification, with some aphid clones carrying up to 100 copies. We conclude that the mutations leading to overexpression of CYP6CY3 were a prerequisite for the host shift of M. persicae to tobacco and that gene amplification and microsatellite polymorphism are evolutionary drivers in insect host adaptation. PMID- 24218583 TI - Keratin 16 regulates innate immunity in response to epidermal barrier breach. AB - Mutations in the type I keratin 16 (Krt16) and its partner type II keratin 6 (Krt6a, Krt6b) cause pachyonychia congenita (PC), a disorder typified by dystrophic nails, painful hyperkeratotic calluses in glabrous skin, and lesions involving other epithelial appendages. The pathophysiology of these symptoms and its relationship to settings in which Krt16 and Krt6 are induced in response to epidermal barrier stress are poorly understood. We report that hyperkeratotic calluses arising in the glabrous skin of individuals with PC and Krt16 null mice share a gene expression signature enriched in genes involved in inflammation and innate immunity, in particular damage-associated molecular patterns. Transcriptional hyper-activation of damage-associated molecular pattern genes occurs following de novo chemical or mechanical irritation to ear skin and in spontaneously arising skin lesions in Krt16 null mice. Genome-wide expression analysis of normal mouse tail skin and benign proliferative lesions reveals a tight, context-dependent coregulation of Krt16 and Krt6 with genes involved in skin barrier maintenance and innate immunity. Our results uncover a role for Krt16 in regulating epithelial inflammation that is relevant to genodermatoses, psoriasis, and cancer and suggest a avenue for the therapeutic management of PC and related disorders. PMID- 24218584 TI - Structural and genetic analyses reveal the protein SepF as a new membrane anchor for the Z ring. AB - A key step in bacterial cell division is the polymerization of the tubulin homolog FtsZ at midcell. FtsZ polymers are anchored to the cell membrane by FtsA and are required for the assembly of all other cell division proteins. In Gram positive and cyanobacteria, FtsZ filaments are aligned by the protein SepF, which in vitro polymerizes into large rings that bundle FtsZ filaments. Here we describe the crystal structure of the only globular domain of SepF, located within the C-terminal region. Two-hybrid data revealed that this domain comprises the FtsZ binding site, and EM analyses showed that it is sufficient for ring formation, which is explained by the filaments in the crystals of SepF. Site directed mutagenesis, gel filtration, and analytical ultracentrifugation indicated that dimers form the basic units of SepF filaments. High-resolution structured illumination microscopy suggested that SepF is membrane associated, and it turned out that purified SepF not only binds to lipid membranes, but also recruits FtsZ. Further genetic and biochemical analyses showed that an amphipathic helix at the N terminus functions as the membrane-binding domain, making SepF a unique membrane anchor for the FtsZ ring. This clarifies why Bacillus subtilis grows without FtsA or the putative membrane anchor EzrA and why bacteria lacking FtsA contain SepF homologs. Both FtsA and SepF use an amphipathic helix for membrane binding. These helices prefer positively curved membranes due to relaxed lipid density; therefore this type of membrane anchor may assist in keeping the Z ring positioned at the strongly curved leading edge of the developing septum. PMID- 24218585 TI - Serotonin selectively enhances perception and sensory neural responses to stimuli generated by same-sex conspecifics. AB - Centrifugal serotonergic fibers innervating sensory brain areas are seen ubiquitously across systems and species but their function remains unclear. Here we examined the functional role of serotonergic innervation onto electrosensory neurons in weakly electric fish by eliciting endogenous release through electrical stimulation as well as exogenous focal application of serotonin in the vicinity of the cell being recorded from. Both approaches showed that the function of serotonergic input onto electrosensory pyramidal neurons is to render them more excitable by reducing the spike afterhyperpolarization amplitude and thereby promoting burst firing. Further, serotonergic input selectively improved neuronal responses to stimuli that occur during interactions between same-sex conspecifics but not to stimuli associated with either prey or that occur during interactions between opposite-sex conspecifics. Finally, we tested whether serotonin-mediated enhanced pyramidal neuron responses to stimuli associated with same-sex conspecifics actually increase perception by the animal. Our behavioral experiments show that exogenous injection and endogenous release of serotonin both increase the magnitude of behavioral responses to stimuli associated with same-sex conspecifics as well as simultaneously decrease aggressive behaviors. Thus, our data indicate that the serotonergic system inhibits aggressive behavior toward same-sex conspecifics, while at the same time increasing perception of stimuli associated with these individuals. This function is likely to be conserved across systems and species. PMID- 24218586 TI - High-affinity olfactory receptor for the death-associated odor cadaverine. AB - Carrion smell is strongly repugnant to humans and triggers distinct innate behaviors in many other species. This smell is mainly carried by two small aliphatic diamines, putrescine and cadaverine, which are generated by bacterial decarboxylation of the basic amino acids ornithine and lysine. Depending on the species, these diamines may also serve as feeding attractants, oviposition attractants, or social cues. Behavioral responses to diamines have not been investigated in zebrafish, a powerful model system for studying vertebrate olfaction. Furthermore, olfactory receptors that detect cadaverine and putrescine have not been identified in any species so far. Here, we show robust olfactory mediated avoidance behavior of zebrafish to cadaverine and related diamines, and concomitant activation of sparse olfactory sensory neurons by these diamines. The large majority of neurons activated by low concentrations of cadaverine expresses a particular olfactory receptor, trace amine-associated receptor 13c (TAAR13c). Structure-activity analysis indicates TAAR13c to be a general diamine sensor, with pronounced selectivity for odd chains of medium length. This receptor can also be activated by decaying fish extracts, a physiologically relevant source of diamines. The identification of a sensitive zebrafish olfactory receptor for these diamines provides a molecular basis for studying neural circuits connecting sensation, perception, and innate behavior. PMID- 24218587 TI - Growth hormone prevents the development of autoimmune diabetes. AB - Evidence supports a relationship between the neuroendocrine and the immune systems. Data from mice that overexpress or are deficient in growth hormone (GH) indicate that GH stimulates T and B-cell proliferation and Ig synthesis, and enhances maturation of myeloid progenitor cells. The effect of GH on autoimmune pathologies has nonetheless been little studied. Using a murine model of type 1 diabetes, a T-cell-mediated autoimmune disease characterized by immune cell infiltration of pancreatic islets and destruction of insulin-producing beta cells, we observed that sustained GH expression reduced prodromal disease symptoms and eliminated progression to overt diabetes. The effect involves several GH-mediated mechanisms; GH altered the cytokine environment, triggered anti-inflammatory macrophage (M2) polarization, maintained activity of the suppressor T-cell population, and limited Th17 cell plasticity. In addition, GH reduced apoptosis and/or increased the proliferative rate of beta-cells. These results support a role for GH in immune response regulation and identify a unique target for therapeutic intervention in type 1 diabetes. PMID- 24218588 TI - Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway. AB - Matrix elasticity regulates proliferation, apoptosis, and differentiation of many cell types across various tissues. In particular, stiffened matrix in fibrotic lesions has been shown to promote pathogenic myofibroblast activation. To better understand the underlying pathways by which fibroblasts mechano-sense matrix elasticity, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves on poly(ethylene glycol)-based hydrogels with physiologically relevant and tunable elasticities. We show that soft hydrogels preserve the quiescent fibroblast phenotype of VICs much better than stiff plastic plates. We demonstrate that the PI3K/AKT pathway is significantly up regulated when VICs are cultured on stiff gels or tissue culture polystyrene compared with freshly isolated VICs. In contrast, myofibroblasts de-activate and pAKT/AKT decreases as early as 2 h after reducing the substrate modulus. When PI3K or AKT is inhibited on stiff substrates, myofibroblast activation is blocked. When constitutively active PI3K is overexpressed, the myofibroblast phenotype is promoted even on soft substrates. These data suggest that valvular fibroblasts are sensing the changes in matrix elasticity through the PI3K/AKT pathway. This mechanism may be used by other mechano-sensitive cells in response to substrate modulus, and this pathway may be a worthwhile target for treating matrix stiffness-associated diseases. Furthermore, hydrogels can be designed to recapitulate important mechanical cues in native tissues to preserve aspects of the native phenotype of primary cells for understanding basic cellular responses to biophysical and biochemical signals, and for tissue-engineering applications. PMID- 24218589 TI - Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins. AB - The rapidly growing recognition of the role of oncogenic ROS1 fusion proteins in the malignant transformation of multiple cancers, including lung adenocarcinoma, cholangiocarcinoma, and glioblastoma, is driving efforts to develop effective ROS1 inhibitors for use as molecularly targeted therapy. Using a multidisciplinary approach involving small molecule screening in combination with in vitro and in vivo tumor models, we show that foretinib (GSK1363089) is a more potent ROS1 inhibitor than crizotinib (PF-02341066), an ALK/ROS inhibitor currently in clinical evaluation for lung cancer patients harboring ROS1 rearrangements. Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non-small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention. We confirm that the ROS1(G2032R) mutant, recently reported in clinical resistance to crizotinib, retains foretinib sensitivity at concentrations below safe, clinically achievable levels. Furthermore, we use an accelerated mutagenesis screen to preemptively identify mutations in the ROS1 kinase domain that confer resistance to crizotinib and demonstrate that these mutants also remain foretinib sensitive. Taken together, our data strongly suggest that foretinib is a highly effective ROS1 inhibitor, and further clinical investigation to evaluate its potential therapeutic benefit for patients with ROS1-driven malignancies is warranted. PMID- 24218590 TI - BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease. AB - Bone morphogenetic protein 9 (BMP9) promotes the acquisition of the cholinergic phenotype in basal forebrain cholinergic neurons (BFCN) during development and protects these neurons from cholinergic dedifferentiation following axotomy when administered in vivo. A decline in BFCN function occurs in patients with Alzheimer's disease (AD) and contributes to the AD-associated memory deficits. We infused BMP9 intracerebroventricularly for 7 d in transgenic AD model mice expressing green fluorescent protein specifically in cholinergic neurons (APP.PS1/CHGFP) and in wild-type littermate controls (WT/CHGFP). We used 5-mo-old mice, an age when the AD transgenics display early amyloid deposition and few cholinergic defects, and 10-mo-old mice, by which time these mice exhibit established disease. BMP9 infusion reduced the number of Abeta42-positive amyloid plaques in the hippocampus and cerebral cortex of 5- and 10-mo-old APP.PS1/CHGFP mice and reversed the reductions in choline acetyltransferase protein levels in the hippocampus of 10-mo-old APP.PS1/CHGFP mice. The treatment increased cholinergic fiber density in the hippocampus of both WT/CHGFP and APP.PS1/CHGFP mice at both ages. BMP9 infusion also increased hippocampal levels of neurotrophin 3, insulin-like growth factor 1, and nerve growth factor and of the nerve growth factor receptors, tyrosine kinase receptor A and p75/NGFR, irrespective of the genotype of the mice. These data show that BMP9 administration is effective in reducing the Abeta42 amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for BFCN in a mouse model of AD and provide evidence that the BMP9-signaling pathway may constitute a therapeutic target for AD. PMID- 24218591 TI - Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration. AB - Parkinson disease (PD) is the most common movement disorder and, although the exact causes are unknown, recent epidemiological and experimental studies indicate that several environmental agents may be significant risk factors. To date, these suspected environmental risk factors have been man-made chemicals. In this report, we demonstrate via genetic, biochemical, and immunological studies that the common volatile fungal semiochemical 1-octen-3-ol reduces dopamine levels and causes dopamine neuron degeneration in Drosophila melanogaster. Overexpression of the vesicular monoamine transporter (VMAT) rescued the dopamine toxicity and neurodegeneration, whereas mutations decreasing VMAT and tyrosine hydroxylase exacerbated toxicity. Furthermore, 1-octen-3-ol also inhibited uptake of dopamine in human cell lines expressing the human plasma membrane dopamine transporter (DAT) and human VMAT ortholog, VMAT2. These data demonstrate that 1 octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism. PMID- 24218593 TI - Intrinsic karyotype stability and gene copy number variations may have laid the foundation for tetraploid wheat formation. AB - Polyploidy or whole-genome duplication is recurrent in plant evolution, yet only a small fraction of whole-genome duplications has led to successful speciation. A major challenge in the establishment of nascent polyploids is sustained karyotype instability, which compromises fitness. The three putative diploid progenitors of bread wheat, with AA, SS (S ~ B), and DD genomes occurred sympatrically, and their cross-fertilization in different combinations may have resulted in fertile allotetraploids with various genomic constitutions. However, only SSAA or closely related genome combinations have led to the speciation of tetraploid wheats like Triticum turgidum and Triticum timopheevii. We analyzed early generations of four newly synthesized allotetraploid wheats with genome compositions S(sh)S(sh)A(m)A(m), S(l)S(l)AA, S(b)S(b)DD, and AADD by combined fluorescence and genomic in situ hybridization-based karyotyping. Results of karyotype analyses showed that although S(sh)S(sh)A(m)A(m) and S(l)S(l)AA are characterized by immediate and persistent karyotype stability, massive aneuploidy and extensive chromosome restructuring are associated with S(b)S(b)DD and AADD in which parental subgenomes showed markedly different propensities for chromosome gain/loss and rearrangements. Although compensating aneuploidy and reciprocal translocation between homeologs prevailed, reproductive fitness was substantially compromised due to chromosome instability. Strikingly, localized genomic changes in repetitive DNA and copy-number variations in gene homologs occurred in both chromosome stable lines, S(sh)S(sh)A(m)A(m) and S(l)S(l)AA. Our data demonstrated that immediate and persistent karyotype stability is intrinsic to newly formed allotetraploid wheat with genome combinations analogous to natural tetraploid wheats. This property, coupled with rapid gene copy-number variations, may have laid the foundation of tetraploid wheat establishment. PMID- 24218594 TI - Site-2 protease substrate specificity and coupling in trans by a PDZ-substrate adapter protein. AB - Site-2 proteases (S2Ps) are intramembrane metalloproteases that cleave transmembrane substrates in all domains of life. Many S2Ps, including human S2P and Mycobacterium tuberculosis Rip1, have multiple substrates in vivo, which are often transcriptional regulators. However, S2Ps will also cleave transmembrane sequences of nonsubstrate proteins, suggesting additional specificity determinants. Many S2Ps also contain a PDZ domain, the function of which is poorly understood. Here, we identify an M. tuberculosis protein, PDZ-interacting protease regulator 1 (Ppr1), which bridges between the Rip1 PDZ domain and anti sigma factor M (Anti-SigM), a Rip1 substrate, but not Anti-SigK or Anti-SigL, also Rip1 substrates. In vivo analyses of Ppr1 function indicate that it prevents nonspecific activation of the Rip1 pathway while coupling Rip1 cleavage of Anti SigM, but not Anti-SigL, to site-1 proteolysis. Our results support a model of S2P substrate specificity in which a substrate-specific adapter protein tethers the S2P to its substrate while holding the protease inactive through its PDZ domain. PMID- 24218592 TI - Symbiotic bacteria appear to mediate hyena social odors. AB - All animals harbor beneficial microbes. One way these microbes can benefit their animal hosts is by increasing the diversity and efficacy of communication signals available to the hosts. The fermentation hypothesis for mammalian chemical communication posits that bacteria in the scent glands of mammals generate odorous metabolites used by their hosts for communication and that variation in host chemical signals is a product of underlying variation in the bacterial communities inhabiting the scent glands. An effective test of this hypothesis would require accurate surveys of the bacterial communities in mammals' scent glands and complementary data on the odorant profiles of scent secretions--both of which have been historically lacking. Here we use next-generation sequencing to survey deeply the bacterial communities in the scent glands of wild spotted and striped hyenas. We show that these communities are dominated by fermentative bacteria and that the structures of these communities covary with the volatile fatty acid profiles of scent secretions in both hyena species. The bacterial and volatile fatty acid profiles of secretions differ between spotted and striped hyenas, and both profiles vary with sex and reproductive state among spotted hyenas within a single social group. Our results strongly support the fermentation hypothesis for chemical communication, suggesting that symbiotic bacteria underlie species-specific odors in both spotted and striped hyenas and further underlie sex and reproductive state-specific odors among spotted hyenas. We anticipate that the fermentation hypothesis for chemical communication will prove broadly applicable among scent-marking mammals as others use the technical and analytical approaches used here. PMID- 24218595 TI - Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb. AB - To date, only the five most posterior groups of Hox genes, Hox9-Hox13, have demonstrated loss-of-function roles in limb patterning. Individual paralog groups control proximodistal patterning of the limb skeletal elements. Hox9 genes also initiate the onset of Hand2 expression in the posterior forelimb compartment, and collectively, the posterior HoxA/D genes maintain posterior Sonic Hedgehog (Shh) expression. Here we show that an anterior Hox paralog group, Hox5, is required for forelimb anterior patterning. Deletion of all three Hox5 genes (Hoxa5, Hoxb5, and Hoxc5) leads to anterior forelimb defects resulting from derepression of Shh expression. The phenotype requires the loss of all three Hox5 genes, demonstrating the high level of redundancy in this Hox paralogous group. Further analyses reveal that Hox5 interacts with promyelocytic leukemia zinc finger biochemically and genetically to restrict Shh expression. These findings, along with previous reports showing that point mutations in the Shh limb enhancer lead to similar anterior limb defects, highlight the importance of Shh repression for proper patterning of the vertebrate limb. PMID- 24218596 TI - Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons. AB - About 12% of human genetic disorders involve premature termination codons (PTCs). Aminoglycoside antibiotics have been proposed for restoring full-length proteins by readthrough of PTC. To assess the efficiency of readthrough, we selected homozygous and compound heterozygous skin fibroblasts from xeroderma pigmentosum (XP) patients with different PTCs in the XPC DNA repair gene. XP patients have a nucleotide excision repair defect and a 10,000-fold increased risk of UV-induced skin cancer. In six of eight PTC-containing XP-C cells, treatment with Geneticin and gentamicin resulted in (i) stabilized XPC-mRNA, which would have been degraded by nonsense-mediated decay; (ii) increased expression of XPC protein that localized to UV-damaged sites; (iii) recruitment of XPB and XPD proteins to UV DNA damage sites; and (iv) increased repair of 6-4 photoproducts and cyclobutane pyrimidine dimers. Expression of PTC in a transfected vector revealed that readthrough depends on the PTC sequence and its location within the gene. This sensitive DNA repair assay system demonstrates the complexity of response to PTC readthrough inducers. The efficiency of aminoglycoside-mediated readthrough depends on the type and copy number of PTC, the downstream 4+ nucleotide, and the location within the exon. Treatment with small-molecule nonaminoglycoside compounds (PTC124, BZ16, or RTC14) resulted in similarly increased XPC mRNA expression and photoproduct removal with less toxicity than with the aminoglycosides. Characterizing PTC structure and parameters governing effective PTC readthrough may provide a unique prophylactic therapy for skin cancer prevention in XP-C patients. PMID- 24218597 TI - Rewriting the rules for end joining via enzymatic splicing of DNA 3'-PO4 and 5' OH ends. AB - There are many biological contexts in which DNA damage generates "dirty" breaks with 3'-PO4 (or cyclic-PO4) and 5'-OH ends that cannot be sealed by DNA ligases. Here we show that the Escherichia coli RNA ligase RtcB can splice these dirty DNA ends via a unique chemical mechanism. RtcB transfers GMP from a covalent RtcB-GMP intermediate to a DNA 3'-PO4 to form a "capped" 3' end structure, DNA3'pp5'G. When a suitable DNA 5'-OH end is available, RtcB catalyzes attack of the 5'-OH on DNA3'pp5'G to form a 3'-5' phosphodiester splice junction. Our findings unveil an enzymatic capacity for DNA 3' capping and the sealing of DNA breaks with 3'-PO4 and 5'-OH termini, with implications for DNA repair and DNA rearrangements. PMID- 24218598 TI - Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans. AB - In many patients with major depressive disorder, sleep deprivation, or wake therapy, induces an immediate but often transient antidepressant response. It is known from brain imaging studies that changes in anterior cingulate and dorsolateral prefrontal cortex activity correlate with a relief of depression symptoms. Recently, resting-state functional magnetic resonance imaging revealed that brain network connectivity via the dorsal nexus (DN), a cortical area in the dorsomedial prefrontal cortex, is dramatically increased in depressed patients. To investigate whether an alteration in DN connectivity could provide a biomarker of therapy response and to determine brain mechanisms of action underlying sleep deprivations antidepressant effects, we examined its influence on resting state default mode network and DN connectivity in healthy humans. Our findings show that sleep deprivation reduced functional connectivity between posterior cingulate cortex and bilateral anterior cingulate cortex (Brodmann area 32), and enhanced connectivity between DN and distinct areas in right dorsolateral prefrontal cortex (Brodmann area 10). These findings are consistent with resolution of dysfunctional brain network connectivity changes observed in depression and suggest changes in prefrontal connectivity with the DN as a brain mechanism of antidepressant therapy action. PMID- 24218599 TI - Motionless phase stepping in X-ray phase contrast imaging with a compact source. AB - X-ray phase contrast imaging offers a way to visualize the internal structures of an object without the need to deposit significant radiation, and thereby alleviate the main concern in X-ray diagnostic imaging procedures today. Grating based differential phase contrast imaging techniques are compatible with compact X-ray sources, which is a key requirement for the majority of clinical X-ray modalities. However, these methods are substantially limited by the need for mechanical phase stepping. We describe an electromagnetic phase-stepping method that eliminates mechanical motion, thus removing the constraints in speed, accuracy, and flexibility. The method is broadly applicable to both projection and tomography imaging modes. The transition from mechanical to electromagnetic scanning should greatly facilitate the translation of X-ray phase contrast techniques into mainstream applications. PMID- 24218600 TI - Searching for efficient Markov chain Monte Carlo proposal kernels. AB - Markov chain Monte Carlo (MCMC) or the Metropolis-Hastings algorithm is a simulation algorithm that has made modern Bayesian statistical inference possible. Nevertheless, the efficiency of different Metropolis-Hastings proposal kernels has rarely been studied except for the Gaussian proposal. Here we propose a unique class of Bactrian kernels, which avoid proposing values that are very close to the current value, and compare their efficiency with a number of proposals for simulating different target distributions, with efficiency measured by the asymptotic variance of a parameter estimate. The uniform kernel is found to be more efficient than the Gaussian kernel, whereas the Bactrian kernel is even better. When optimal scales are used for both, the Bactrian kernel is at least 50% more efficient than the Gaussian. Implementation in a Bayesian program for molecular clock dating confirms the general applicability of our results to generic MCMC algorithms. Our results refute a previous claim that all proposals had nearly identical performance and will prompt further research into efficient MCMC proposals. PMID- 24218601 TI - Synthetic lethality between CCNE1 amplification and loss of BRCA1. AB - High-grade serous ovarian cancers (HGSCs) are characterized by a high frequency of TP53 mutations, BRCA1/2 inactivation, homologous recombination dysfunction, and widespread copy number changes. Cyclin E1 (CCNE1) gene amplification has been reported to occur independently of BRCA1/2 mutation, and it is associated with primary treatment failure and reduced patient survival. Insensitivity of CCNE1 amplified tumors to platinum cross-linking agents may be partly because of an intact BRCA1/2 pathway. Both BRCA1/2 dysfunction and CCNE1 amplification are known to promote genomic instability and tumor progression. These events may be mutually exclusive, because either change provides a path to tumor development, with no selective advantage to having both mutations. Using data from a genome wide shRNA synthetic lethal screen, we show that BRCA1 and members of the ubiquitin pathway are selectively required in cancers that harbor CCNE1 amplification. Furthermore, we show specific sensitivity of CCNE1-amplified tumor cells to the proteasome inhibitor bortezomib. These findings provide an explanation for the observed mutual exclusivity of CCNE1 amplification and BRCA1/2 loss in HGSC and suggest a unique therapeutic approach for treatment resistant CCNE1-amplified tumors. PMID- 24218602 TI - Three-dimensional textures and defects of soft material layering revealed by thermal sublimation. AB - Layering is found and exploited in a variety of soft material systems, ranging from complex macromolecular self-assemblies to block copolymer and small-molecule liquid crystals. Because the control of layer structure is required for applications and characterization, and because defects reveal key features of the symmetries of layered phases, a variety of techniques have been developed for the study of soft-layer structure and defects, including X-ray diffraction and visualization using optical transmission and fluorescence confocal polarizing microscopy, atomic force microscopy, and SEM and transmission electron microscopy, including freeze-fracture transmission electron microscopy. Here, it is shown that thermal sublimation can be usefully combined with such techniques to enable visualization of the 3D structure of soft materials. Sequential sublimation removes material in a stepwise fashion, leaving a remnant layer structure largely unchanged and viewable using SEM, as demonstrated here using a lamellar smectic liquid crystal. PMID- 24218603 TI - Differential effects of global versus local testosterone on singing behavior and its underlying neural substrate. AB - Steroid hormones regulate multiple but distinct aspects of social behaviors. Testosterone (T) has multiple effects on learned courtship song in that it regulates both the motivation to sing in a particular social context as well as the quality of song produced. The neural substrate(s) where T acts to regulate the motivation to sing as opposed to other aspects of song has not been definitively characterized. We show here that T implants in the medial preoptic nucleus (POM) of castrated male canaries (Serinus canaria) increase song rate but do not enhance acoustic features such as song stereotypy compared with birds receiving peripheral T that can act globally throughout the brain. Strikingly, T action in the POM increased song control nuclei volume, consistent with the hypothesis that singing activity induces neuroplasticity in the song control system independent of T acting in these nuclei. When presented with a female canary, POM-T birds copulated at a rate comparable to birds receiving systemic T but produced fewer calls and songs in her presence. Thus, POM is a key site where T acts to activate copulation and increase song rate, an appetitive sexual behavior in songbirds, but T action in other areas of the brain or periphery (e.g., HVC, dopaminergic cell groups, or the syrinx) is required to enhance the quality of song (i.e., stereotypy) as well as regulate context-specific vocalizations. These results have broad implications for research concerning how steroids act at multiple brain loci to regulate distinct sociosexual behaviors and the associated neuroplasticity. PMID- 24218604 TI - Frequency-specific mechanism links human brain networks for spatial attention. AB - Selective attention allows us to filter out irrelevant information in the environment and focus neural resources on information relevant to our current goals. Functional brain-imaging studies have identified networks of broadly distributed brain regions that are recruited during different attention processes; however, the dynamics by which these networks enable selection are not well understood. Here, we first used functional MRI to localize dorsal and ventral attention networks in human epileptic subjects undergoing seizure monitoring. We subsequently recorded cortical physiology using subdural electrocorticography during a spatial-attention task to study network dynamics. Attention networks become selectively phase-modulated at low frequencies (delta, theta) during the same task epochs in which they are recruited in functional MRI. This mechanism may alter the excitability of task-relevant regions or their effective connectivity. Furthermore, different attention processes (holding vs. shifting attention) are associated with synchrony at different frequencies, which may minimize unnecessary cross-talk between separate neuronal processes. PMID- 24218605 TI - Arabidopsis thaliana AHL family modulates hypocotyl growth redundantly by interacting with each other via the PPC/DUF296 domain. AB - The Arabidopsis thaliana genome encodes 29 AT-hook motif containing nuclear localized (AHL) genes, which evolved into two phylogenic clades. The AHL proteins contain one or two AT-hook motif(s) and one plant and prokaryote conserved (PPC)/domain of unknown function #296 (DUF296) domain. Seedlings lacking both SOB3/AHL29 and ESC/AHL27 confer a subtle long-hypocotyl phenotype compared with the WT or either single-null mutant. In contrast, the missense allele sob3-6 confers a dramatic long-hypocotyl phenotype in the light. In this study, we examined the dominant-negative feature of sob3-6 and found that it encodes a protein with a disrupted AT-hook motif that abolishes binding to AT-rich DNA. A loss-of-function approach demonstrated different, yet redundant, contributions of additional AHL genes in suppressing hypocotyl elongation in the light. We showed that AHL proteins interact with each other and themselves via the PPC/DUF296 domain. AHLs also share interactions with other nuclear proteins, such as transcription factors, suggesting that these interactions also contribute to the functional redundancy within this gene family. The coordinated action of AHLs requires an AT-hook motif capable of binding AT-rich DNA, as well as a PPC/DUF296 domain containing a conserved Gly-Arg-Phe-Glu-Ile-Leu region. Alteration of this region abolished SOB3/AHL29's physical interaction with transcription factors and resulted in a dominant-negative allele in planta that was phenotypically similar to sob3-6. We propose a molecular model where AHLs interact with each other and themselves, as well as other nuclear proteins, to form complexes which modulate plant growth and development. PMID- 24218606 TI - Antitumor activities of agonistic anti-TNFR antibodies require differential FcgammaRIIB coengagement in vivo. AB - Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fcgamma receptor FcgammaRIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally deleted for FcgammaRIIB on defined cellular populations or mutated in specific signaling components, we now demonstrate that different agonistic anti-TNFR antibodies have specific requirements for FcgammaRIIB expression on defined cellular populations and function in trans in the absence of FcgammaRIIB signaling components, thus supporting a general mechanism of FcgammaRIIB cross-linking in vivo for the activities of these antibodies. PMID- 24218608 TI - David Hubel retrospective. PMID- 24218607 TI - Islet amyloid polypeptide toxicity and membrane interactions. AB - Islet amyloid polypeptide (IAPP) is responsible for amyloid formation in type 2 diabetes and contributes to the failure of islet cell transplants, however the mechanisms of IAPP-induced cytotoxicity are not known. Interactions with model anionic membranes are known to catalyze IAPP amyloid formation in vitro. Human IAPP damages anionic membranes, promoting vesicle leakage, but the features that control IAPP-membrane interactions and the connection with cellular toxicity are not clear. Kinetic studies with wild-type IAPP and IAPP mutants demonstrate that membrane leakage is induced by prefibrillar IAPP species and continues over the course of amyloid formation, correlating additional membrane disruption with fibril growth. Analyses of a set of designed mutants reveal that membrane leakage does not require the formation of beta-sheet or alpha-helical structures. A His 18 to Arg substitution enhances leakage, whereas replacement of all of the aromatic residues via a triple leucine mutant has no effect. Biophysical measurements in conjunction with cytotoxicity studies show that nonamyloidogenic rat IAPP is as effective as human IAPP at disrupting standard anionic model membranes under conditions where rat IAPP does not induce cellular toxicity. Similar results are obtained with more complex model membranes, including ternary systems that contain cholesterol and are capable of forming lipid rafts. A designed point mutant, I26P-IAPP; a designed double mutant, G24P, I26P-IAPP; a double N-methylated variant; and pramlintide, a US Food and Drug Administration approved IAPP variant all induce membrane leakage, but are not cytotoxic, showing that there is no one-to-one relationship between disruption of model membranes and induction of cellular toxicity. PMID- 24218609 TI - Mechanism of IAPP amyloid fibril formation involves an intermediate with a transient beta-sheet. AB - Amyloid formation is implicated in more than 20 human diseases, yet the mechanism by which fibrils form is not well understood. We use 2D infrared spectroscopy and isotope labeling to monitor the kinetics of fibril formation by human islet amyloid polypeptide (hIAPP or amylin) that is associated with type 2 diabetes. We find that an oligomeric intermediate forms during the lag phase with parallel beta-sheet structure in a region that is ultimately a partially disordered loop in the fibril. We confirm the presence of this intermediate, using a set of homologous macrocyclic peptides designed to recognize beta-sheets. Mutations and molecular dynamics simulations indicate that the intermediate is on pathway. Disrupting the oligomeric beta-sheet to form the partially disordered loop of the fibrils creates a free energy barrier that is the origin of the lag phase during aggregation. These results help rationalize a wide range of previous fragment and mutation studies including mutations in other species that prevent the formation of amyloid plaques. PMID- 24218610 TI - Impact of reconstituted cytosol on protein stability. AB - Protein stability is usually studied in simple buffered solutions, but most proteins function inside cells, where the heterogeneous and crowded environment presents a complex, nonideal system. Proteins are expected to behave differently under cellular crowding owing to two types of contacts: hard-core repulsions and weak, chemical interactions. The effect of hard-core repulsions is purely entropic, resulting in volume exclusion owing to the mere presence of the crowders. The weak interactions can be repulsive or attractive, thus enhancing or diminishing the excluded volume, respectively. We used a reductionist approach to assess the effects of intracellular crowding. Escherichia coli cytoplasm was dialyzed, lyophilized, and resuspended at two concentrations. NMR-detected amide proton exchange was then used to quantify the stability of the globular protein chymotrypsin inhibitor 2 (CI2) in these crowded solutions. The cytosol destabilizes CI2, and the destabilization increases with increasing cytosol concentration. This observation shows that the cytoplasm interacts favorably, but nonspecifically, with CI2, and these interactions overcome the stabilizing hard core repulsions. The effects of the cytosol are even stronger than those of homogeneous protein crowders, reinforcing the biological significance of weak, nonspecific interactions. PMID- 24218611 TI - Similarity increases altruistic punishment in humans. AB - Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics--a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others' uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions. PMID- 24218612 TI - Gene product 0.4 increases bacteriophage T7 competitiveness by inhibiting host cell division. AB - Bacteriophages take over host resources primarily via the activity of proteins expressed early in infection. One of these proteins, produced by the Escherichia coli phage T7, is gene product (Gp) 0.4. Here, we show that Gp0.4 is a direct inhibitor of the E. coli filamenting temperature-sensitive mutant Z division protein. A chemically synthesized Gp0.4 binds to purified filamenting temperature sensitive mutant Z protein and directly inhibits its assembly in vitro. Consequently, expression of Gp0.4 in vivo is lethal to E. coli and results in bacteria that are morphologically elongated. We further show that this inhibition of cell division by Gp0.4 enhances the bacteriophage's competitive ability. This division inhibition is thus a fascinating example of a strategy in bacteriophages to maximize utilization of their hosts' cell resources. PMID- 24218613 TI - Host-induced gene silencing of cytochrome P450 lanosterol C14alpha-demethylase encoding genes confers strong resistance to Fusarium species. AB - Head blight, which is caused by mycotoxin-producing fungi of the genus Fusarium, is an economically important crop disease. We assessed the potential of host induced gene silencing targeting the fungal cytochrome P450 lanosterol C-14alpha demethylase (CYP51) genes, which are essential for ergosterol biosynthesis, to restrict fungal infection. In axenic cultures of Fusarium graminearum, in vitro feeding of CYP3RNA, a 791-nt double-stranded (ds)RNA complementary to CYP51A, CYP51B, and CYP51C, resulted in growth inhibition [half-maximum growth inhibition (IC50) = 1.2 nM] as well as altered fungal morphology, similar to that observed after treatment with the azole fungicide tebuconazole, for which the CYP51 enzyme is a target. Expression of the same dsRNA in Arabidopsis and barley rendered susceptible plants highly resistant to fungal infection. Microscopic analysis revealed that mycelium formation on CYP3RNA-expressing leaves was restricted to the inoculation sites, and that inoculated barley caryopses were virtually free of fungal hyphae. This inhibition of fungal growth correlated with in planta production of siRNAs corresponding to the targeted CYP51 sequences, as well as highly efficient silencing of the fungal CYP51 genes. The high efficiency of fungal inhibition suggests that host-induced gene-silencing targeting of the CYP51 genes is an alternative to chemical treatments for the control of devastating fungal diseases. PMID- 24218614 TI - Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer. AB - We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, we found that plectin cell surface localization was attributable to its presence in exosomes secreted from PDAC cells, which is dependent on the expression of integrin beta4, a protein known to interact with cytosolic plectin. Moreover, plectin expression was necessary for efficient exosome production and was required to sustain enhanced tumor growth in immunodeficient and in immunocompetent mice. It is now clear that this PDAC biomarker plays a role in PDAC, and further understanding of plectin's contribution to PDAC could enable improved therapies. PMID- 24218615 TI - Global methylation state at base-pair resolution of the Caulobacter genome throughout the cell cycle. AB - The Caulobacter DNA methyltransferase CcrM is one of five master cell-cycle regulators. CcrM is transiently present near the end of DNA replication when it rapidly methylates the adenine in hemimethylated GANTC sequences. The timing of transcription of two master regulator genes and two cell division genes is controlled by the methylation state of GANTC sites in their promoters. To explore the global extent of this regulatory mechanism, we determined the methylation state of the entire chromosome at every base pair at five time points in the cell cycle using single-molecule, real-time sequencing. The methylation state of 4,515 GANTC sites, preferentially positioned in intergenic regions, changed progressively from full to hemimethylation as the replication forks advanced. However, 27 GANTC sites remained unmethylated throughout the cell cycle, suggesting that these protected sites could participate in epigenetic regulatory functions. An analysis of the time of activation of every cell-cycle regulatory transcription start site, coupled to both the position of a GANTC site in their promoter regions and the time in the cell cycle when the GANTC site transitions from full to hemimethylation, allowed the identification of 59 genes as candidates for epigenetic regulation. In addition, we identified two previously unidentified N(6)-methyladenine motifs and showed that they maintained a constant methylation state throughout the cell cycle. The cognate methyltransferase was identified for one of these motifs as well as for one of two 5-methylcytosine motifs. PMID- 24218616 TI - Structural and functional insights into the regulation mechanism of CK2 by IP6 and the intrinsically disordered protein Nopp140. AB - Protein kinase CK2 is a ubiquitous kinase that can phosphorylate hundreds of cellular proteins and plays important roles in cell growth and development. Deregulation of CK2 is related to a variety of human cancers, and CK2 is regarded as a suppressor of apoptosis; therefore, it is a target of anticancer therapy. Nucleolar phosphoprotein 140 (Nopp140), which is an intrinsically disordered protein, interacts with CK2 and inhibits the latter's catalytic activity in vitro. Interestingly, the catalytic activity of CK2 is recovered in the presence of d-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). IP6 is widely distributed in animal cells, but the molecular mechanisms that govern its cellular functions in animal cells have not been completely elucidated. In this study, the crystal structure of CK2 in complex with IP6 showed that the lysine-rich cluster of CK2 plays an important role in binding to IP6. The biochemical experiments revealed that a Nopp140 fragment (residues 568-596) and IP6 competitively bind to the catalytic subunit of CK2 (CK2alpha), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2alpha. Substitutions of K74E, K76E, and K77E in CK2alpha significantly reduced the interactions of CK2alpha with both IP6 and the Nopp140-derived peptide. Our study gives an insight into the regulation of CK2. In particular, our work suggests that CK2 activity is inhibited by Nopp140 and reactivated by IP6 by competitive binding at the substrate recognition site of CK2. PMID- 24218617 TI - Phototropic growth control of nanoscale pattern formation in photoelectrodeposited Se-Te films. AB - Photoresponsive materials that adapt their morphologies, growth directions, and growth rates dynamically in response to the local incident electromagnetic field would provide a remarkable route to the synthesis of complex 3D mesostructures via feedback between illumination and the structure that develops under optical excitation. We report the spontaneous development of ordered, nanoscale lamellar patterns in electrodeposited selenium-tellurium (Se-Te) alloy films grown under noncoherent, uniform illumination on unpatterned substrates in an isotropic electrolyte solution. These inorganic nanostructures exhibited phototropic growth in which lamellar stripes grew toward the incident light source, adopted an orientation parallel to the light polarization direction with a period controlled by the illumination wavelength, and showed an increased growth rate with increasing light intensity. Furthermore, the patterns responded dynamically to changes during growth in the polarization, wavelength, and angle of the incident light, enabling the template-free and pattern-free synthesis, on a variety of substrates, of woodpile, spiral, branched, or zigzag structures, along with dynamically directed growth toward a noncoherent, uniform intensity light source. Full-wave electromagnetic simulations in combination with Monte Carlo growth simulations were used to model light-matter interactions in the Se-Te films and produced a model for the morphological evolution of the lamellar structures under phototropic growth conditions. The experiments and simulations are consistent with a phototropic growth mechanism in which the optical near-field intensity profile selects and reinforces the dominant morphological mode in the emergent nanoscale patterns. PMID- 24218619 TI - Comprehensive analysis of imprinted genes in maize reveals allelic variation for imprinting and limited conservation with other species. AB - In plants, a subset of genes exhibit imprinting in endosperm tissue such that expression is primarily from the maternal or paternal allele. Imprinting may arise as a consequence of mechanisms for silencing of transposons during reproduction, and in some cases imprinted expression of particular genes may provide a selective advantage such that it is conserved across species. Separate mechanisms for the origin of imprinted expression patterns and maintenance of these patterns may result in substantial variation in the targets of imprinting in different species. Here we present deep sequencing of RNAs isolated from reciprocal crosses of four diverse maize genotypes, providing a comprehensive analysis that allows evaluation of imprinting at more than 95% of endosperm expressed genes. We find that over 500 genes exhibit statistically significant parent-of-origin effects in maize endosperm tissue, but focused our analyses on a subset of these genes that had >90% expression from the maternal allele (69 genes) or from the paternal allele (108 genes) in at least one reciprocal cross. Over 10% of imprinted genes show evidence of allelic variation for imprinting. A comparison of imprinting in maize and rice reveals that 13% of genes with syntenic orthologs in both species exhibit conserved imprinting. Genes that exhibit conserved imprinting between maize and rice have elevated nonsynonymous to synonymous substitution ratios compared with other imprinted genes, suggesting a history of more rapid evolution. Together, these data suggest that imprinting only has functional relevance at a subset of loci that currently exhibit imprinting in maize. PMID- 24218620 TI - Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response. AB - L-type Ca(2+) currents conducted by CaV1.2 channels initiate excitation contraction coupling in the heart. Their activity is increased by beta adrenergic/cAMP signaling via phosphorylation by PKA in the fight-or-flight response, but the sites of regulation are unknown. We describe the functional role of phosphorylation of Ser1700 and Thr1704-sites of phosphorylation by PKA and casein kinase II at the interface between the proximal and distal C-terminal regulatory domains. Mutation of both residues to Ala in STAA mice reduced basal L type Ca(2+) currents, due to a small decrease in expression and a substantial decrease in functional activity. The increase in L-type Ca(2+) current caused by isoproterenol was markedly reduced at physiological levels of stimulation (3-10 nM). Maximal increases in calcium current at nearly saturating concentrations of isoproterenol (100 nM) were also significantly reduced, but the mutation effects were smaller, suggesting that alternative regulatory mechanisms are engaged at maximal levels of stimulation. The beta-adrenergic increase in cell contraction was also diminished. STAA ventricular myocytes exhibited arrhythmic contractions in response to isoproterenol, and up to 20% of STAA cells failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. We conclude that phosphorylation of Ser1700 and Thr1704 is essential for regulation of basal activity of CaV1.2 channels and for up-regulation by beta-adrenergic signaling at physiological levels of stimulation. Disruption of phosphorylation at those sites leads to impaired cardiac function in vivo, as indicated by reduced exercise capacity and cardiac hypertrophy. PMID- 24218621 TI - Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways. AB - In the trachea and bronchi of the mouse, airway smooth muscle (SM) and cartilage are localized to complementary domains surrounding the airway epithelium. Proper juxtaposition of these tissues ensures a balance of elasticity and rigidity that is critical for effective air passage. It is unknown how this tissue complementation is established during development. Here we dissect the developmental relationship between these tissues by genetically disrupting SM formation (through Srf inactivation) or cartilage formation (through Sox9 inactivation) and assessing the impact on the remaining lineage. We found that, in the trachea and main bronchi, loss of SM or cartilage resulted in an increase in cell number of the remaining lineage, namely the cartilage or SM, respectively. However, only in the main bronchi, but not in the trachea, did the loss of SM or cartilage lead to a circumferential expansion of the remaining cartilage or SM domain, respectively. In addition to SM defects, cartilage deficient tracheas displayed epithelial phenotypes, including decreased basal cell number, precocious club cell differentiation, and increased secretoglobin expression. These findings together delineate the mechanisms through which a cell autonomous disruption of one structural tissue can have widespread consequences on upper airway function. PMID- 24218624 TI - Comminution of solids caused by kinetic energy of high shear strain rate, with implications for impact, shock, and shale fracturing. AB - Although there exists a vast literature on the dynamic comminution or fragmentation of rocks, concrete, metals, and ceramics, none of the known models suffices for macroscopic dynamic finite element analysis. This paper outlines the basic idea of the macroscopic model. Unlike static fracture, in which the driving force is the release of strain energy, here the essential idea is that the driving force of comminution under high-rate compression is the release of the local kinetic energy of shear strain rate. The density of this energy at strain rates >1,000/s is found to exceed the maximum possible strain energy density by orders of magnitude, making the strain energy irrelevant. It is shown that particle size is proportional to the -2/3 power of the shear strain rate and the 2/3 power of the interface fracture energy or interface shear stress, and that the comminution process is macroscopically equivalent to an apparent shear viscosity that is proportional (at constant interface stress) to the -1/3 power of this rate. A dimensionless indicator of the comminution intensity is formulated. The theory was inspired by noting that the local kinetic energy of shear strain rate plays a role analogous to the local kinetic energy of eddies in turbulent flow. PMID- 24218622 TI - Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. AB - Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor beta (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4( )CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins. PMID- 24218625 TI - Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. AB - Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2+) elevations with rapid onset and short duration in a large proportion of cortical astrocytes in the adult mouse somatosensory cortex. Our improved detection of the fast Ca(2+) signals is due to a signal-enhancing analysis of the Ca(2+) activity. The rapid stimulation-evoked Ca(2+) increases identified in astrocyte somas, processes, and end-feet preceded local vasodilatation. Fast Ca(2+) responses in both neurons and astrocytes correlated with synaptic activity, but only the astrocytic responses correlated with the hemodynamic shifts. These data establish that a large proportion of cortical astrocytes have brief Ca(2+) responses with a rapid onset in vivo, fast enough to initiate hemodynamic responses or influence synaptic activity. PMID- 24218626 TI - The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway. AB - The transport protein particle (TRAPP) III complex, comprising the TRAPPI complex and additional subunit Trs85, is an autophagy-specific guanine nucleotide exchange factor for the Rab GTPase Ypt1 that is recruited to the phagophore assembly site when macroautophagy is induced. We present the single-particle electron microscopy structure of TRAPPIII, which reveals that the dome-shaped Trs85 subunit associates primarily with the Trs20 subunit of TRAPPI. We further demonstrate that TRAPPIII binds the coat protein complex (COP) II coat subunit Sec23. The COPII coat facilitates the budding and targeting of ER-derived vesicles with their acceptor compartment. We provide evidence that COPII-coated vesicles and the ER-Golgi fusion machinery are needed for macroautophagy. Our results imply that TRAPPIII binds to COPII vesicles at the phagophore assembly site and that COPII vesicles may provide one of the membrane sources used in autophagosome formation. These events are conserved in yeast to mammals. PMID- 24218627 TI - New insights into epididymal function in relation to sperm maturation. AB - Testicular spermatozoa acquire fertility only after 1 or 2 weeks of transit through the epididymis. At the end of this several meters long epididymal tubule, the male gamete is able to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte to result in a viable embryo. All these sperm properties are acquired after sequential modifications occurring either at the level of the spermatozoon or in the epididymal surroundings. Over the last few decades, significant increases in the understanding of the composition of the male gamete and its surroundings have resulted from the use of new techniques such as genome sequencing, proteomics combined with high sensitivity mass spectrometry, and gene-knockout approaches. This review reports and discusses the most relevant new results obtained in different species regarding the various cellular processes occurring at the sperm level, in particular, those related to the development of motility and egg binding during epididymal transit. PMID- 24218628 TI - No association between exposure to perfluorinated compounds and congenital cryptorchidism: a nested case-control study among 215 boys from Denmark and Finland. AB - Geographical differences in the occurrence of diseases in male reproductive organs, including malformation in reproductive tract, between Denmark and Finland have been reported. The reason for these differences is unknown, but differences in exposure to chemicals with endocrine-disrupting abilities have been suggested. Among these chemicals are perfluoro-alkylated substances (PFASs), a group of water- and grease-repellent chemicals used in outdoor clothes, cookware, food packaging, and textiles. In this study, we, therefore, investigated differences in PFAS exposure levels between Denmark and Finland and the association between cord blood PFAS levels and congenital cryptorchidism. Boys from a joint ongoing prospective birth cohort study were included. We analyzed PFAS levels in cord blood serum samples collected from 29 Danish boys with congenital cryptorchidism, 30 healthy Danish matched controls recruited from 1997 to 2001, 30 Finnish cases, and 78 Finnish healthy matched controls recruited from 1997 to 1999. Additionally, 48 Finnish cases recruited from 2000 to 2002 were included. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were detected in all the 215 Danish and Finnish cord blood samples with significantly higher levels being observed in the Danish samples (medians: PFOA, 2.6 ng/ml and PFOS, 9.1 ng/ml) than in the Finnish samples (medians: PFOA, 2.1 ng/ml and PFOS, 5.2 ng/ml). We found no associations between cord blood PFOA and PFOS levels and congenital cryptorchidism after adjustment for confounders. Our data indicate that women in Denmark and Finland are generally exposed to PFOA and PFOS but there are differences in exposure levels between countries. We found no statistically significant association between cord blood PFOA and PFOS levels and congenital cryptorchidism; however, our study was small and larger studies are warranted. PMID- 24218629 TI - Involvement of hyaluronan synthesis in ovarian follicle growth in rats. AB - Most of the previous studies on ovarian hyaluronan (HA) have focused on mature antral follicles or corpora lutea, but scarcely on small preantral follicles. Moreover, the origin of follicular HA is unknown. To clarify the localization of HA and its synthases in small growing follicles, involvement of HA in follicle growth, and gonadotropin regulation of HA synthase (Has) gene expression, in this study, perinatal, immature, and adult ovaries of Wistar-Imamichi rats were examined histologically and biochemically and by in vitro follicle culture. HA was detected in the extracellular matrix of granulosa and theca cell layers of primary follicles and more advanced follicles. Ovarian HA accumulation ontogenetically started in the sex cords of perinatal rats, and its primary site shifted to the intrafollicular region of primary follicles within 5 days of birth. The Has1-3 mRNAs were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels of Has1 and Has2 genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins in immature acyclic rats. The Has1 and Has2 mRNAs were predominantly localized in the theca and granulosa cell layers of growing follicles respectively. Treatments with chemicals known to reduce ovarian HA synthesis induced follicular atresia. More directly, the addition of Streptomyces hyaluronidase, which specifically degrades HA, induced the arrest of follicle growth in an in vitro culture system. These results indicate that gonadotropin regulated HA synthesis is involved in normal follicle growth. PMID- 24218630 TI - Evolution of transcriptional enhancers and animal diversity. AB - Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field. PMID- 24218631 TI - Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution. AB - In the era of functional genomics, the role of transcription factor (TF)-DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients. We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp, wingless and stripe, by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes. PMID- 24218632 TI - A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice. AB - The developmental brain gene NPAS3 stands out as a hot spot in human evolution because it contains the largest number of human-specific, fast-evolving, conserved, non-coding elements. In this paper we studied 2xHAR142, one of these elements that is located in the fifth intron of NPAS3. Using transgenic mice, we show that the mouse and chimp 2xHAR142 orthologues behave as transcriptional enhancers driving expression of the reporter gene lacZ to a similar NPAS3 expression subdomain in the mouse central nervous system. Interestingly, the human 2xHAR142 orthologue drives lacZ expression to an extended expression pattern in the nervous system. Thus, molecular evolution of 2xHAR142 provides the first documented example of human-specific heterotopy in the forebrain promoted by a transcriptional enhancer and suggests that it may have contributed to assemble the unique properties of the human brain. PMID- 24218633 TI - Deep conservation of cis-regulatory elements in metazoans. AB - Despite the vast morphological variation observed across phyla, animals share multiple basic developmental processes orchestrated by a common ancestral gene toolkit. These genes interact with each other building complex gene regulatory networks (GRNs), which are encoded in the genome by cis-regulatory elements (CREs) that serve as computational units of the network. Although GRN subcircuits involved in ancient developmental processes are expected to be at least partially conserved, identification of CREs that are conserved across phyla has remained elusive. Here, we review recent studies that revealed such deeply conserved CREs do exist, discuss the difficulties associated with their identification and describe new approaches that will facilitate this search. PMID- 24218635 TI - Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution. AB - The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis-regulatory elements) in entire genomes. Comparing protein-DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein-DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression. PMID- 24218634 TI - The mystery of extreme non-coding conservation. AB - Regions of several dozen to several hundred base pairs of extreme conservation have been found in non-coding regions in all metazoan genomes. The distribution of these elements within and across genomes has suggested that many have roles as transcriptional regulatory elements in multi-cellular organization, differentiation and development. Currently, there is no known mechanism or function that would account for this level of conservation at the observed evolutionary distances. Previous studies have found that, while these regions are under strong purifying selection, and not mutational coldspots, deletion of entire regions in mice does not necessarily lead to identifiable changes in phenotype during development. These opposing findings lead to several questions regarding their functional importance and why they are under strong selection in the first place. In this perspective, we discuss the methods and techniques used in identifying and dissecting these regions, their observed patterns of conservation, and review the current hypotheses on their functional significance. PMID- 24218636 TI - Adaptive divergence of a transcriptional enhancer between populations of Drosophila melanogaster. AB - As species colonize new habitats they must adapt to the local environment. Much of this adaptation is thought to occur at the regulatory level; however, the relationships among genetic polymorphism, expression variation and adaptation are poorly understood. Drosophila melanogaster, which expanded from an ancestral range in sub-Saharan Africa around 15 000 years ago, represents an excellent model system for studying regulatory evolution. Here, we focus on the gene CG9509, which differs in expression between an African and a European population of D. melanogaster. The expression difference is caused by variation within a transcriptional enhancer adjacent to the CG9509 coding sequence. Patterns of sequence variation indicate that this enhancer was the target of recent positive selection, suggesting that the expression difference is adaptive. Analysis of the CG9509 enhancer in new population samples from Europe, Asia, northern Africa and sub-Saharan Africa revealed that sequence polymorphism is greatly reduced outside the ancestral range. A derived haplotype absent in sub-Saharan Africa is at high frequency in all other populations. These observations are consistent with a selective sweep accompanying the range expansion of the species. The new data help identify the sequence changes responsible for the difference in enhancer activity. PMID- 24218637 TI - Many human accelerated regions are developmental enhancers. AB - The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology. PMID- 24218638 TI - Assessing constraints on the path of regulatory sequence evolution. AB - Structural and functional constraints are known to play a major role in restricting the path of evolution of protein activities. However, constraints acting on evolving transcriptional regulatory sequences, e.g. enhancers, are largely unknown. Recently, we elucidated how a novel expression pattern of the Neprilysin-1 (Nep1) gene in the optic lobe of Drosophila santomea evolved via co option of existing enhancer activities. Drosophila santomea, which has diverged from Drosophila yakuba by approximately 400 000 years has accumulated four fixed mutations that each contribute to the full activity of this enhancer. Recreating and testing the optic lobe enhancer of the ancestor of D. santomea and D. yakuba revealed that the strong D. santomea enhancer activity evolved from a weak ancestral activity. Because each mutation on the path from the D. yakuba/santomea ancestor to modern-day D. santomea contributes to the newly derived optic lobe enhancer activity, we sought here to use this system to study the path of evolution of enhancer sequences. We inferred likely paths of evolution of this enhancer by observing the transcriptional output of all possible intermediate steps between the ancestral D. yakuba/santomea enhancer and the modern D. santomea enhancer. Many possible paths had epistatic and cooperative effects. Furthermore, we found that several paths significantly increased ectopic transcriptional activity or affected existing enhancer activities from which the novel activity was co-opted. We suggest that these attributes highlight constraints that guide the path of evolution of enhancers. PMID- 24218639 TI - Enhancer turnover and conserved regulatory function in vertebrate evolution. AB - Mutations in regulatory regions including enhancers are an important source of variation and innovation during evolution. Enhancers can evolve by changes in the sequence, arrangement and repertoire of transcription factor binding sites, but whole enhancers can also be lost or gained in certain lineages in a process of turnover. The proopiomelanocortin gene (Pomc), which encodes a prohormone, is expressed in the pituitary and hypothalamus of all jawed vertebrates. We have previously described that hypothalamic Pomc expression in mammals is controlled by two enhancers-nPE1 and nPE2-that are derived from transposable elements and that presumably replaced the ancestral neuronal Pomc regulatory regions. Here, we show that nPE1 and nPE2, even though they are mammalian novelties with no homologous counterpart in other vertebrates, nevertheless can drive gene expression specifically to POMC neurons in the hypothalamus of larval and adult transgenic zebrafish. This indicates that when neuronal Pomc enhancers originated de novo during early mammalian evolution, the newly created cis- and trans-codes were similar to the ancestral ones. We also identify the neuronal regulatory region of zebrafish pomca and confirm that it is not homologous to the mammalian enhancers. Our work sheds light on the process of gene regulatory evolution by showing how a locus can undergo enhancer turnover and nevertheless maintain the ancestral transcriptional output. PMID- 24218642 TI - Low-level gamma and neutron monitoring based on use of proportional counter filled with 3He in polythene moderator: study of the responses to gamma and neutrons. AB - It has been shown that a proportional counter filled with (3)He placed centrally inside a polythene sphere opens a new possibility for measuring gamma photons and neutrons in the separate pulse-height windows. The responses to gamma and neutrons (in terms of ambient dose equivalent) of the detector assembly consisting of 203-mm polythene sphere with centrally positioned 40-mm diameter (3)He proportional counter have been studied. The response to secondary gammas from capture process in hydrogen has also been studied. The rather preliminary studies indicate that the proposed measuring system has very promising features as an ambient dose equivalent device for mixed gamma-neutron fields. PMID- 24218640 TI - The structure and evolution of cis-regulatory regions: the shavenbaby story. AB - In this paper, we provide a historical account of the contribution of a single line of research to our current understanding of the structure of cis-regulatory regions and the genetic basis for morphological evolution. We revisit the experiments that shed light on the evolution of larval cuticular patterns within the genus Drosophila and the evolution and structure of the shavenbaby gene. We describe the experiments that led to the discovery that multiple genetic changes in the cis-regulatory region of shavenbaby caused the loss of dorsal cuticular hairs (quaternary trichomes) in first instar larvae of Drosophila sechellia. We also discuss the experiments that showed that the convergent loss of quaternary trichomes in D. sechellia and Drosophila ezoana was generated by parallel genetic changes in orthologous enhancers of shavenbaby. We discuss the observation that multiple shavenbaby enhancers drive overlapping patterns of expression in the embryo and that these apparently redundant enhancers ensure robust shavenbaby expression and trichome morphogenesis under stressful conditions. All together, these data, collected over 13 years, provide a fundamental case study in the fields of gene regulation and morphological evolution, and highlight the importance of prolonged, detailed studies of single genes. PMID- 24218644 TI - Induced electric fields in the MAXWEL surface-based human model from exposure to external low frequency electric fields. AB - This work presents calculations of internal induced electric fields in the anatomically realistic surface-based model of the male human body, MAXWEL, from exposure to external low frequency electric fields under grounded and isolated conditions. The maximum 99th percentile induced electric fields calculated in the MAXWEL central nervous system were 3.49 (grounded) and 1.54 (isolated) mV m(-1) per kV m(-1) at 50 Hz. The application of 2, 1 and 0.5 mm resolution voxel models derived from the surface-based version to the calculations of induced electric fields is described. 2 mm and 1 mm resolution maximum 99th percentile induced electric field values calculated in selected tissues of the eye at 50 Hz were within 30 % of those calculated at 0.5 mm resolution. The calculated electric field values in MAXWEL were compared with values from the male model NORMAN and female model NAOMI. The maximum 99th percentile value for NAOMI, calculated by Dimbylow in bone, was 49.4 mV m(-1) per kV m(-1) at 50 Hz under grounded conditions. The corresponding value calculated in MAXWEL was 15.7 mV m(-1) per kV m(-1), considerably lower due to anatomical differences between the male and female models. PMID- 24218641 TI - Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements. AB - Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and 'through-DNA' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex. PMID- 24218643 TI - An attempt to decrease anisotropic emissions of neutrons from a cylindrical 241Am Be-encapsulation source. AB - An attempt to decrease the anisotropic emissions of neutrons from a cylindrical (241)Am-Be-encapsulated X3 source was conducted with Monte Carlo calculations and experiments. The influence of metal materials and shapes of the external casing to the anisotropy factor were focussed on. Results obtained by calculations using MCNP4C implied that a light and spherical-shaped external casing decreases the anisotropic emission of neutrons. Experimental results using the spherical-shaped aluminium protection case also revealed that the anisotropy factor was close to 1.0 with wide zenith angle ranges. PMID- 24218645 TI - Sindh, Pakistan: home to South-Asia's first HIV law. PMID- 24218646 TI - Reaudit of laboratory diagnostic methods for syphilis 2011. PMID- 24218647 TI - Commentary. PMID- 24218648 TI - Retraction notice to "Antitumor and immunomodulatory activity of a polysaccharide from fungus Coprinus comatus (Mull.:Fr.) Gray" [Int. J. Biol. Macromol 58 (2013) 349-353]. PMID- 24218649 TI - HIV-infected women in Europe: gender-specific needs and challenges. AB - In collaboration with the Strong, HIV positive, Empowered Women (SHE) programme, an industry-funded initiative aimed at improving the quality of life of HIV positive women, Antiviral Therapy has taken the excellent step to dedicate a Supplement Issue addressing the needs and challenges related to the care of women living in Europe. Included articles present the multiple facets of gender specific issues and research gaps, ranging from HIV testing strategies to antiretroviral combination therapy, including long-term challenges associated with chronic HIV infection. PMID- 24218650 TI - Response. PMID- 24218651 TI - Response. PMID- 24218652 TI - Response. PMID- 24218654 TI - Gastrointestinal quality of life following bariatric surgery in Asian patients. AB - BACKGROUND/AIMS: Bariatric surgery is the only proven method that produces sustained weight loss. We aimed to investigate the Gastrointestinal Quality of Life Index (GIQLI) differences between obese patients following laparoscopic mini gastric bypass (LMGB), laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in this study. METHODOLOGY: From December 2005 to December 2007, we enrolled 152 patients who received bariatric surgery, including 41 men and 111 women, mean age 32.6+/-9.4 years and mean BMI 37.4+/ 7.9kg/m2 (range 32.0-64.9). Clinical characteristics and quality of life were analyzed. RESULTS: One year after bariatric surgery, the mean general score of GIQLI improved significantly (p=0.000). All patients had improvement in three domains of the questionnaire (social function, physical status and emotional status) but not in gastrointestinal symptoms. The preoperative general score was 105.9+/-15.4 points in LMGB group, 110.9+/-14.8 points in LAGB group and 99.0+/ 19.8 points in LSG group, respectively. Despite a significant difference between three groups regarding preoperative GIQLI scores (p=0.001), the 1-year results failed to show any significant difference in a comparison of postoperative GIQLI scores (p=0.082). CONCLUSIONS: In conclusion, our study has demonstrated significant improvement in quality of life 1-year after laparoscopic bariatric surgery. The improvement of GIQLI scores in three domains of social function, physical status and emotional status can be offered to obese patients before surgery. PMID- 24218655 TI - Neuroscience: A head start for brain imaging. PMID- 24218656 TI - Head start. PMID- 24218657 TI - Historic work. PMID- 24218658 TI - Follow the crowd. PMID- 24218659 TI - Uncertain inheritance transgenerational effects of environmental exposures. PMID- 24218660 TI - Neuroscience: My life with Parkinson's. PMID- 24218661 TI - Diseases: Study neuron networks to tackle Alzheimer's. PMID- 24218663 TI - Retraction notice to "Bacterial lipopolysaccharide-induced oxidative stress in adult rat Sertoli cells in vitro" [Toxicol. Vitro 24 (2010) 1266-72]. PMID- 24218662 TI - A new breed of model: estimating the impact of climate change on malaria transmission. PMID- 24218664 TI - Prenatal protection: maternal diet may modify impact of PAHs. PMID- 24218665 TI - Arsenic handicap? Prenatal exposure worsens influenza infections in young mice. PMID- 24218666 TI - Molecular competition: flame retardants interact with key metabolism enzyme. PMID- 24218667 TI - Response. PMID- 24218668 TI - Response. PMID- 24218669 TI - Acute motor-sensory axonal neuropathy and Helicobacter pylori infections. PMID- 24218670 TI - Response. PMID- 24218671 TI - Shale gas extraction in North Carolina: research recommendations and public health implications. PMID- 24218672 TI - Childhood lead poisoning in China: challenges and opportunities. PMID- 24218673 TI - Urinary cadmium as a marker of exposure in epidemiological studies. PMID- 24218674 TI - Urinary cadmium as a marker of exposure in epidemiological studies: Bernard and Chaumont respond. PMID- 24218675 TI - The Minamata Convention on Mercury: a first step toward protecting future generations. PMID- 24218676 TI - Response. PMID- 24218677 TI - Response. PMID- 24218678 TI - [Reply]. PMID- 24218679 TI - NICHE solutions--fifth in a series: focus on communication. PMID- 24218680 TI - Resident satisfaction in assisted living. PMID- 24218681 TI - [Distal forearm fractures - ultrasonography for diagnosis in children is very helpful]. PMID- 24218682 TI - [Accurate localization and detection by dual source ct scan]. PMID- 24218683 TI - [Evidence of coronary heart disease: automatic or manual?]. PMID- 24218684 TI - [Discrimination in MRI]. PMID- 24218685 TI - [18F-Nsodiumfluorid/18F-FDG-PET/CT shows promising results]. PMID- 24218686 TI - [Neurovascular compression as a cause?]. PMID- 24218687 TI - Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Author reply. PMID- 24218688 TI - The brave new world of oncology research. PMID- 24218689 TI - Are you fit for duty? PMID- 24218690 TI - Population health: strategies that deliver value and results. PMID- 24218692 TI - Want more staff? It's all about the data. PMID- 24218691 TI - Are you tired, overworked? You must be a case manager. AB - Case managers are being asked to take on more and more tasks, but the caseloads haven't changed, resulting in tired case managers who aren't able to do the job adequately. Make sure the hospital administration understands what case managers do and the value they bring to the organization. Consider developing specialty positions or adding clerical staff to optimize skill sets for staff. Use hard data, not anecdotes, when you make your case to management. PMID- 24218693 TI - Productivity tool measures CM success. AB - Case management leadership at Northwestern-Lake Forest Hospital has developed a capacity and productivity tool that tracks the work and efficiency of the case management staff. The department tabulated the average time it takes case managers to complete each case management task and tracks the time each case manager spends on tasks each day. The tool can be used to show the productivity of an individual, a unit, or the entire department. Department leadership shares reports with management and uses it in employees'annual evaluations. PMID- 24218694 TI - Peer interviews, mentors = happy case managers. AB - New case managers at Carolinas HealthCare System are chosen by their peers and as part of orientation, work closely with a preceptor, then meet with a mentor for a year. Case managers who will be working with the new hire interview candidates and make the final selection. The preceptor follows them as they complete the case management training orientation program that includes hands-on training. When they start their new job, they are assigned a mentor who meets regularly with them for a year and is available for questions and concerns. PMID- 24218696 TI - Engage family members in crucial conversations. PMID- 24218695 TI - Tailor ED discharge plan to the individual. AB - A study by Penn Medicine that examined why low-income patients seek care in the emergency department concluded that the healthcare system drives patients away from primary care and to the emergency department. Low-income patients have to miss work and line up transportation to make a primary care visit. Often, their providers are in clinics with a limited number of appointments each day. Instead of merely lecturing patients about seeking care at the right level, case managers should develop strategies to meet each patient's individual needs. PMID- 24218697 TI - Robert P. Perry 1931-2013. PMID- 24218698 TI - Drs. Lim and Feldman reply. PMID- 24218699 TI - Special issue dedicated to Navin S. Scrimshaw. PMID- 24218701 TI - Editorial: From "information technology in biomedicine" to "biomedical and health informatics". PMID- 24218700 TI - Equipment location in hospitals using RFID-based positioning system. AB - Throughout various complex processes within hospitals, context-aware services and applications can help to improve the quality of care and reduce costs. For example, sensors and radio frequency identification (RFID) technologies for e health have been deployed to improve the flow of material, equipment, personal, and patient. Bed tracking, patient monitoring, real-time logistic analysis, and critical equipment tracking are famous applications of real-time location systems (RTLS) in hospitals. In fact, existing case studies show that RTLS can improve service quality and safety, and optimize emergency management and time critical processes. In this paper, we propose a robust system for position and orientation determination of equipment. Our system utilizes passive (RFID) technology mounted on flooring plates and several peripherals for sensor data interpretation. The system is implemented and tested through extensive experiments. The results show that our system's average positioning and orientation measurement outperforms existing systems in terms of accuracy. The details of the system as well as the experimental results are presented in this paper. PMID- 24218702 TI - Guest editorial: Multimedia services and technologies for e-health (MUST-EH). PMID- 24218703 TI - An intelligent scoring system and its application to cardiac arrest prediction. AB - Traditional risk score prediction is based on vital signs and clinical assessment. In this paper, we present an intelligent scoring system for the prediction of cardiac arrest within 72 h. The patient population is represented by a set of feature vectors, from which risk scores are derived based on geometric distance calculation and support vector machine. Each feature vector is a combination of heart rate variability (HRV) parameters and vital signs. Performance evaluation is conducted on the leave-one-out cross-validation framework, and receiver operating characteristic, sensitivity, specificity, positive predictive value, and negative predictive value are reported. Experimental results reveal that the proposed scoring system not only achieves satisfactory performance on determining the risk of cardiac arrest within 72 h but also has the ability to generate continuous risk scores rather than a simple binary decision by a traditional classifier. Furthermore, the proposed scoring system works well for both balanced and imbalanced datasets, and the combination of HRV parameters and vital signs shows superiority in prediction to using HRV parameters only or vital signs only. PMID- 24218704 TI - Response. PMID- 24218705 TI - Categorization and segmentation of intestinal content frames for wireless capsule endoscopy. AB - Wireless capsule endoscopy (WCE) is a device that allows the direct visualization of gastrointestinal tract with minimal discomfort for the patient, but at the price of a large amount of time for screening. In order to reduce this time, several works have proposed to automatically remove all the frames showing intestinal content. These methods label frames as {intestinal content- clear} without discriminating between types of content (with different physiological meaning) or the portion of image covered. In addition, since the presence of intestinal content has been identified as an indicator of intestinal motility, its accurate quantification can show a potential clinical relevance. In this paper, we present a method for the robust detection and segmentation of intestinal content in WCE images, together with its further discrimination between turbid liquid and bubbles. Our proposal is based on a twofold system. First, frames presenting intestinal content are detected by a support vector machine classifier using color and textural information. Second, intestinal content frames are segmented into {turbid, bubbles, and clear} regions. We show a detailed validation using a large dataset. Our system outperforms previous methods and, for the first time, discriminates between turbid from bubbles media. PMID- 24218706 TI - [New concept on old disease. Preface]. PMID- 24218707 TI - [Modeling of lateral amyotrophic sclerosis: a non-genetic method]. PMID- 24218708 TI - [Venous encephalopathy. Possibilities of diagnosis and treatment]. PMID- 24218709 TI - [Treatment of Parkinson's disease: original drugs and generics]. PMID- 24218710 TI - [The 11th weekend school for neurologists of St. Petersburg and the North-West Federal region <>]. PMID- 24218711 TI - [The XI Russian school for young psychiatrists]. PMID- 24218712 TI - Sounding the alarm. Nurses, organizations work to address alarm fatigue. PMID- 24218713 TI - At the push of a button. Patients, nurses use apps to augment health care. PMID- 24218714 TI - OpenNotes initiative aims to improve patient-clinician communication, care. PMID- 24218715 TI - Texas hospital approaches technology with eye toward patient safety, nursing practice. PMID- 24218716 TI - Profile: an adventurer at nursing's frontiers expands the profession's scope and efficacy. PMID- 24218717 TI - Ready to serve, ready to lead. PMID- 24218718 TI - The hidden crime: human trafficking. AB - As the primary contact in the health care system, nurses can play a role in combating this crime and assisting the victims. Assessment for abuse, neglect, trauma, recurrent sexually transmitted infections (STIs) and fear of a controlling partner is critical. Following up on "red flags" and understanding methods of safe questioning can make the difference between slavery and recovery for victims. Nurses must also know the professional referrals in their areas once a potential victim has been identified. This may be a very dangerous undertaking and must be handled by experienced personnel. Referrals to forensic nurses or physicians, domestic violence professionals or law enforcement may be indicated. Initially, a nurse may want to consult with the agency social worker for guidance. Human trafficking is a human rights crime. Unfortunately, it is more prevalent in all types of communities than most people suspect. Nurses can be heroes to the victims through understanding of this crime and vigilance in the assessment and care of all people they encounter in their practices. PMID- 24218720 TI - Knowing your neighbors. A brief overview of Fort Jackson, and its behavioral health services. PMID- 24218719 TI - Enduring echoes. An unlikely candidate: a southern belle at Johns Hopkins School of Nursing, 1893-1894. PMID- 24218721 TI - Children and backpack safety. PMID- 24218722 TI - Have we conquered lateral violence? PMID- 24218723 TI - Measuring communication competency. The next step in addressing disruptive behavior. PMID- 24218724 TI - [School refusal]. PMID- 24218725 TI - [School refusal and dropping out of school: positioning regarding a Swiss perspective]. AB - This article deals with refusal to attend school and dropping out of school from the point of view of child and adolescent psychiatry and psychology, in German speaking countries and from the perspective of Swiss schools and their administrative bodies. General epidemiological data on refusal to attend school show that approximately 5% of children and adolescents are likely to try to avoid attending school at some point. There is very little data available on the frequency of school drop-out. In the past two years (2011 and 2012), approximately 2% of all patients seen for the first time at the department of Child and Adolescent Psychiatry, University Zurich, were referred because of failure to attend school, making this phenomenon one of the most common reasons for referral in child and adolescent psychiatry. After a discussion of the epidemiology, symptomatology, causes and its risk factors, the article presents examples drawn from practice and guidelines for intervention in cases of refusal to attend school, and discusses ways of preventing school drop-out from the point of view of schools, hospitals and bodies such as educational psychology services in Switzerland. PMID- 24218726 TI - [School absenteeism in Germany: prevalence of excused and unexcused absenteeism and its correlation with emotional and behavioural problems]. AB - Data about the prevalence of school absenteeism and its correlation with emotional and behavioural problems in Germany is scarce, in particular regarding excused absenteeism. This study aims to close the gap by examining a sample of 2,679 pupils attending the different types of secondary school (Hauptschule, Realschule, Gymnasium), who participated in a clinical trial for the prevention of truancy (WE-STAY-Project). Pupils' mean age was 14 years (M = 13.94, SD = 0.85, Range = 11-19) and gender distribution was balanced (49.35% males, 50.65% females). Using a self-report questionnaire, pupils where asked on how many days they had missed school on average per month during the last school year (excused and unexcused). Emotional and behavioural problems were measured by using the "Strengths and Difficulties Questionnaire" (SDQ). 4.1% of the pupils reported to have missed school without a valid excuse on more than four days per month (unexcused absenteeism). 6.1% had missed school having an excuse on more than ten days per month (excused absenteeism). Both, unexcused and excused absenteeism, showed an increase of emotional and behavioural problems dependent on the intensity of absenteeism. In conclusion, these findings show the relevance of school absenteeism in Germany. In the future, more attention should be given to pupils with also excused absenteeism. PMID- 24218727 TI - [Long-term stability of inpatient cognitive-behavioral therapy of adolescents with anxious-depressed school absenteeism]. AB - 90 adolescents (aged 12-18 years) with chronic anxious-depressive school absenteeism with or without comorbid disruptive symptoms underwent an open inpatient treatment. The treatment was manual guided with a cognitive-behavioral focus. In case of long lasting school absence youth were integrated on a special school initially. The present analyses cover 2- and 9-months follow-ups. At discharge continuous school attendance was achieved by 83 (92.2%) adolescents, by 75 (83.3%) at 2-month and by 63 (70.0%) at 9-month follow-up. For youth with school absenteeism within the follow-up interval absence rates were only minor. The rate of adolescents visiting the special school decreased from 40 (44.4%) at discharge to 24 (26.7%) 9 month later. Associated mental health problems were assessed using standardized questionnaires in self and parent ratings. Small to medium statistically significant aggravations were found. Within the follow-up interval 2/3 of the samplhe underwent an outpatient, weekly cognitive-behavioral treatment. These results must be interpreted with caution because of the lack of a control condition and of concomitant interventions during inpatient treatment. PMID- 24218728 TI - [Effectiveness of early prevention programs in Germany: a systematic review and a meta-analysis]. AB - The number of scientific evaluations of early preventions programs has considerably increased since the foundation of the national center of early prevention in Germany. Early primary and secondary intervention programs are designed to address parents with little children (prenatal until three years) to improve the parent-child-relationship and parental educational competencies. This is thought to enhance child development and to avoid maltreatment in terms of neglect and abuse. During a systematic review, six data-bases were searched for publications on studies about the effectiveness of early prevention programs in Germany between 2003 and 2013. Eight studies were found to fulfill inclusion criteria and were included in a meta-analysis. In comparison to the control groups the early prevention programs had a small effect on maternal symptom burden (d = 0.28), however there was no effect on maternal competences (d = 0.10) and perceived social support (d = -0.06). In addition, there was no effect on psychic child development (d = 0.05) but no effect on the physical development of the children (d = 0.00). Results are discussed as preliminary due to a current lack of a sufficient amount of studies in Germany. PMID- 24218729 TI - [Systemic sclerosis]. AB - Systemic sclerosis (scleroderma) is a rare connective tissue disease characterized by vasculopathy and immune dysfunction, leading to fibrosis with damage of multiple organs. Two major clinical subtypes are the diffuse and limited forms. The combination of Raynaud's phenomenon, puffy fingers and positive antinuclear antibodies are red flag features that should alert the clinician to the presence of very early systemic sclerosis, which can be treated with vasodilator, antithrombotic, and immunosuppressive drugs. Progress has been made even in the management of the most severe manifestations, including interstitial lung disease, pulmonary artery hypertension and scleroderma renal crisis. PMID- 24218730 TI - [The changing spectrum of childhood fractures]. AB - Every third child sustains a fracture before adulthood. Forearm fractures comprise one third of all fractures and their incidence has significantly increased during the past decades. Hand and foot fractures are also common but their number has decreased. A small proportion of children sustain multiple long bone fractures or vertebral fractures. They should be referred to a pediatric evaluation to detect and treat potential underlying bone fragility. PMID- 24218731 TI - [Early diagnosis of Alzheimer's disease]. AB - As a progressive neuropathologic process, Alzheimer's disease is detectable already more than 20 years before the appearance of clinical symptoms. Magnetic resonance imaging is the tool for early diagnosis. Protein assays of the cerebrospinal fluid are available for differential diagnostic problem cases. While early diagnosis of patients suffering from mild cognitive impairment enables targeting of follow-up and medication to the patients in need thereof, the clinical use of biological markers for the recognition of the disease in symptomless patients is not considered allowed before effective registered drug therapy is available for the disease. PMID- 24218732 TI - [The expanding spectrum of LGMD--recently discovered disease genes are important also in Finnish patients]. AB - Limb-girdle muscular dystrophies (LGMD) are autosomal disorders with a range of manifestations varying from almost asymptomatic late-onset patients to severe childhood onset forms. Recently identified disease genes explain the majority of LGMD cases in Finland. Prognosis, potential cardiac and respiratory complications and symptomatic treatment options differ in different LGMD subtypes. This means that the gold standard of diagnosis is the molecular genetic definition of the disease in each patient. Despite evolving sequencing techniques, the clinical, pathological, neurophysiological and imaging characterisation of patients will not become obsolete, but rather, even more important during the next years to enable targeted genetic diagnostics. PMID- 24218733 TI - [Development of substance use disorders can be prevented]. AB - The first experiments with intoxicants take place in early adolescence, and the drug use habits become established during adolescence. In addition to an early start of substance abuse and adolescent drug problems, especially ADHD and behavior disorders predispose to subsequent substance use disorders. Prevention and effective treatment of these disturbances can decrease the risk of subsequent development of substance use disorders. Drug policy decisions are applied to influence the availability of alcohol. Early and adequate interventions in adolescent drug abuse may prevent the development of symptoms into a disorder among the young at risk. PMID- 24218734 TI - [Assessment of an addiction psychiatric patient within primary health care]. AB - Assessment of addiction psychiatric patients during the hectic work at a community health center is a challenging task. A more precise survey of the substance abuse and mental problem can be started by using various screening questionnaires. In devising the treatment plan, focus will initially be on the main problem, and upon prolonged cooperation a more precise survey of the drug and mental problem will be carried out. The patient's overall picture should be considered, avoiding a split treatment of the drug problem and the mental problem. Assessment of psychotic addiction patients belongs to a psychiatrist and the treatment in most cases to specialized care. PMID- 24218735 TI - [Motivating interview and its effectiveness in the treatment of dual diagnosis patients]. AB - Motivating interview is a talking therapeutic way to meet with the patient. The aim is to increase the patient's readiness for change by making her/him talk in favor of the change. In dual diagnosis patients, motivating interview has been found to improve commitment to treatment and to decrease drug abuse more than other equally brief interventions at least over a follow-up period of 3 to 6 months. When integrated with a more extensive therapy, motivating interview improved the treatment response to conventional therapy. The approach seems to be especially suitable for incoherent and reluctant patients PMID- 24218736 TI - [Pharmacological therapy of an addiction psychiatric patient]. AB - Properly conducted pharmacological therapy is expected to improve the prognosis of both the psychic disturbance and the substance abuse problem. Considering the extent of the problem there is, however, relatively little evidence-based knowledge of pharmacological therapy of an addiction psychiatric patient. Separation of psychiatric therapy from addiction therapy may hamper the realization of coherent pharmacological therapy. Psychosocial forms of therapy, especially motivating talking therapies, constitute the most pivotal part of treatment. In addition to the patient's own aims, the interactions of smoking, drugs and medicines must be considered in the planning of the pharmacological therapy. PMID- 24218737 TI - [Addiction psychiatry in specialized care--towards more precise differential diagnosis]. AB - A mental disorder and a substance abuse problem are often present simultaneously. Possible underlying substance abuse is surveyed in examining psychic symptoms. Screening of the substance abuse problem facilitates revealing the presence of previously unrecognized substance abuse problems. Screening of alcohol abuse with the AUDIT questionnaire is necessary for all patients in psychiatric specialized care. The DAST-20 questionnaire is utilized in the screening of drug abuse. The DSM-IV diagnosis system and the PRISM interview define more closely the differential diagnosis associated with dual diagnoses. Treatment of a substance abuse problem related to severe mental disorders should be conducted in an integrated manner by the same treatment unit. PMID- 24218738 TI - [Patient having personality disturbance with substance abuse in psychotherapy]. AB - Due to their destructive nature, substance abuse problems are challenging, their recognition, approach and treatment having all been problematic issues. Because of shame, confessing the problem is difficult also for the patients. Any approach based on confrontation has a negative effect on both commitment to treatment and treatment results. Through one of my patients I describe methods in the treatment of an addition psychiatry patient. PMID- 24218739 TI - The Heritage of Anesthesia by Patrick Sim. PMID- 24218740 TI - Primer on medical history for anesthesiologists: introduction. PMID- 24218741 TI - Mount Auburn Cemetery and its importance to the history of anesthesia. PMID- 24218742 TI - The role of simulation training in medicine. PMID- 24218743 TI - The Jade Goody legacy has undoubtedly saved lives, but what will be the Michael Douglas effect? PMID- 24218744 TI - Paediatric HIV: the experience in Ireland 2004-2011. AB - Despite effective prevention strategies paediatric HIV infection remains an important condition in Ireland. To characterise presentation and identify barriers to optimal management a retrospective chart review of HIV-infected children presenting in Ireland, 2004-2011 was undertaken. Forty-two HIV-infected children were identified; (25 male). Median age at presentation was 6 years (range 0-16 years). 38 children (90%) were born to African mothers. Eleven (26%) were born in Ireland. Twenty-five (59%) were late diagnoses; 11 were symptomatic. Ten of 12 foreign born HIV-infected children had antiretroviral exposure with frequent resistance associated mutations. Seven of 8 children with stage C disease had previously been admitted to hospital in Ireland before diagnosis. Maternal non-adherence to recommendations and seroconversion in pregnancy challenge the goal of paediatric HIV eradication. Targeted strategies for women at risk of infection in pregnancy are required. Late HIV diagnosis remains common, highlighting the need for a more proactive approach to HIV testing. PMID- 24218745 TI - Barriers to accepting and completing latent tuberculosis infection treatment. AB - Treatment of Latent Tuberculosis Infection (LTBI) is an important component of any TB control strategy. Acceptance and completion of treatment is poor. We undertook this study to identify barriers to acceptance & completion of treatment. Patients attending TB clinics completed a self-administered survey. Medical notes and electronic pharmacy records were reviewed. 143 surveys were completed. 70 (49%) completed treatment. Patients were less likely to accept treatment (p = 0.01, RR 0.781, CI 0.643-0.950) and less likely to complete treatment (p = 0.01, RR 0.640, CI 0.462-0.885) when concerned about the side effects of LTBI medication. Completion of LTBI treatment is sub-optimal. The major barrier identified was fear about side effects caused by LTBI medications. PMID- 24218746 TI - Long-term follow up for colon cancer in a minimally invasive, colorectal unit. AB - Our aim was to assess the long-term survival advantage associated with the laparoscopic approach for colon cancer resection in an Irish minimally invasive unit. Between January 2005 and December 2006, 154 patients underwent resection for colon cancer. 108 underwent a laparoscopic resection, with a conversion rate of 11%. The overall 5 year survival was 71.4%. The overall 5 year survival rate for laparoscopic resections was 80.6% where as the overall survival for open resection was 50%. Laparoscopic surgery had a significant 5 year overall survival advantage compared to open in both non metastatic disease (Stage I and II) (92.2% vs. 69.6%, p = 0.0288) and metastatic disease (Stage III and IV), (68.4% vs. 30.4%, p = 0.0026). Laparoscopic surgery in a dedicated minimally invasive unit with verifiable low conversion rates is feasible and in our experience associated with a long-term survival advantage for colon cancer. PMID- 24218747 TI - Chronic disease management in patients attending Irish General Practice training practices. AB - Complexity and workload for patients with chronic diseases in General Practice are poorly understood. Government policy envisages moving workload into primary care. Data was obtained from a GP delivered survey (58 GPs/33 practices) of 160 patients with one or more chronic diseases, and by concurrently extracting data from the patients electronic medical record. Care is physician intensive (average number GP visits 9.2 pa), with limited input from Practice Nurses (1.62 visits pa). Care co-ordination is significant, given complex co morbidity, polypharmacy (average number of medications per patient = 6.8), and numbers of OPDs attended (3.8). Over a quarter of patients (51/160 (27%)) required assistance attending their GP; 60 (31%) self rated their health as fair/poor. Patients are positively disposed towards transfer of care to General Practice. This study provides baseline data on complexity/workload in care delivered in GP Training practices, before implementation of change. PMID- 24218748 TI - Operative surgical yield from general surgical outpatient clinics; time to change the way we practice? AB - The aim of this study was to compare the number of patients attending surgical outpatient clinics in a general hospital to the number of resulting elective procedures scheduled in a single year. Patients initially assessed at private consulting rooms are not included in this study. The number of surgical outpatient appointments issued in 2011 totalled 6503 with non-attendances running at 1489 (22.9%). The number of elective surgical theatre cases performed in 2011 (i.e. the surgical yield from that period) came to 1078 with an additional 1470 patients referred for endoscopy and 475 patients referred for minor operations. Operative surgical yield from the currently structured outpatient clinic model is low, with the number of theatre cases coming to only 16.58% of the original number of outpatient appointments issued. Recommendations for the improvement of outpatient services are made. These findings are relevant in the context of streamlining access to surgical services. PMID- 24218749 TI - Seppuku: a modern approach to an ancient injury. AB - A 67 year-old man with paraplegia and depression presented with self-inflicted evisceration and small bowel injury. Damage control surgery was undertaken at emergency laparotomy with definitive anastomosis performed at second-look laparotomy following 24 hours resuscitation in ICU. He had an uncomplicated post operative course and was discharged to an inpatient psychiatric unit. PMID- 24218750 TI - Life threatening sepsis while on high dose steroids requiring extra-corporeal membrane oxygenation. AB - We present a case of life-threatening streptococcal sepsis in a young man with a history of Behcet's disease within two weeks of commencing high dose corticosteroid therapy for an exacerbation of Behcet's disease. PMID- 24218751 TI - The National Single Assessment Tool (SAT) a pilot study in older persons care survey results. AB - Following a consultation and review process, the interRAI suite of assessment tools was chosen as the most suitable instrument for assessment of the care needs of older people in Ireland. We used previously validated questionnaires to examine the usability, practicality and acceptability of these tools to professionals, carers and clients in rural and urban acute, long-term care and community settings. Of the 45 professionals, 42-44 (93-98%) agreed or strongly agreed with 14 of 15 positive statements regarding the acceptability, clinical value and ease of use of the interRAl tools; 39 (87%) felt the terminology was consistent and familiar, although 35 (78%) felt some areas would require further explanation. Responses from carers (n = 15) and clients (n = 68) were similarly overwhelmingly positive regarding the experience of being assessed using these tools. These results support the clinical utility and practicality of using this approach to assess older people in Irish clinical practice. PMID- 24218753 TI - Re: Preparing new doctors for clinical practice: an evaluation of pre-internship training. PMID- 24218752 TI - A dermatology outpatient waiting list initiative. AB - Skin disease is the most common reason for people to present to their general practitioner (GP) with a new episode of disease. In April 2010 there were estimated 23,000 patients on dermatology outpatient waiting lists in Ireland, including almost 11,000 patients waiting over 6 months. We analysed the data of 200 dermatology outpatient visits scheduled under an initiative to target patients waiting more than 120 days for a new dermatology outpatient appointment. There were 171 (85.5%) patients seen, 29 (14.5%) patients did not attend the appointment. The data from 161 patients seen under the initiative was included in the analysis. Skin lesions accounted for 81 (50%) referrals, of these 71 (44%) patients had benign skin lesions and 10 (6%) patients were considered to have suspicious skin lesions. There was no case of malignant melanoma. After the initial consultation, 66% (106) of the patients were discharged to their primary care physician. PMID- 24218754 TI - Use of oxygen blenders for neonatal resuscitation. PMID- 24218755 TI - Ocular chemical burns in a paediatric population. PMID- 24218756 TI - Smokers need not apply. PMID- 24218757 TI - Society of Psychiatric Advanced Practice Nurses honors Munoz, Kelly, Austin-Benn, and Drake. PMID- 24218758 TI - Nurses helping nurses. PMID- 24218759 TI - The Promise of Stardust. PMID- 24218760 TI - Helping to save lives: overdose prevention legislation signed into law in NJ. PMID- 24218761 TI - [Molecular epidemiology of Panton-Valentine leukocidin (PVL) -positive Staphylococcus aureus associated with skin and soft tissue infection]. AB - Panton-Valentine leukocidin (PVL) secreted by Staphylococcus aureus is known to cause severe skin, soft tissue and lung infections. To assess the prevalence and genetic characteristics of PVL-positive S. aureus in our hospital, we investigated 86 S. aureus isolates isolated from skin and soft tissue pus between September 2011 and May 2012 at Daisan Hospital, the Jikei University School of Medicine (Tokyo, Japan). All isolates were investigated for the mecA gene and PVL gene by PCR amplification. The MRSA isolates confirmed were genotyped using SCCmec typing. PVL-gene positive isolates confirmed by the PVL-RPLA (reverse passive latex agglutination) assay were characterized by agr typing and multilocus sequence typing (MLST). Overall 6 (3 MSSA isolates and 3 MRSA isolates) PVL-positive strains (7.0%) were detected. The PVL prevalence was 11.1% in MRSA and 5.1% in MSSA. PVL-positive strains were isolated from young adults (range: 8-47 years) outpatient. Patients infected with PVL-positive MRSA were significantly younger than those infected with PVL-negative MRSA(32 and 68 years, respectively; P = 0.009, t-test). The 6 PVL positive strains were assigned by the MLST to 6 STs that were prevalent among PVL-positive strains. The SCCmec type of the PVL-positive MRSA were classified into 2 types (type IV or V) that were generally characteristic of CA-MRSA. Our data are consistent with some previous reports showing that PVL gene is found in certain ST strains. The PVL-positive strain must be taken into account when S. aureus is isolated from young adult SSTI. PMID- 24218762 TI - [Usefulness of the standardized serum cystatin C reagent in evaluation of renal function]. AB - Serum cystatin C (sCysC) is valuable to evaluate the renal functions in various clinically studies. Since the reagents to detect sCysC are different among institutes or hospitals, the accidental error due to the difference of reagents is not negligible. That is why sCysC is sometimes difficult to use or interpret for patient as estimated Glomerular filtration rate (eGFR) that is one of the most popular factors to evaluate renal function. Recently, the international reference standard is gradually accepted as standardization of chemical measurement of sCysC in Japan. Japan Society of Clinical Chemistry has reported the utilities for sCysC measurement standardization in 2010. In this study, we examined the usefulness of the standardization of sCysC reagent in Chiba University Hospital. Our study indicated that the clinical usefulness of eGFR calculated by sCysC. As results, eGFR from serum creatinine (sCr) was relatively high in patients with reduced muscle mass, such as old-age patients with wheelchair and prolonged hospitalization. On the other hand, eGFR from sCysC was high in patients with hypothyroidism. Together, eGFR calculated by sCysC is clinically available for the patients with reduced muscle mass could be underestimated. Further studies are required to evaluate the validity of standardization of sCysC measurement and find the dissociation among eGFR, sCysC and sCr depending in the renal disease or pathogenesis. PMID- 24218763 TI - [Clinical and microbiological features of patients with pulmonary nontuberculous mycobacterial infection]. AB - BACKGROUNDS: The prevalence of pulmonary nontuberculous mycobacterial infection (pNTM) is currently increasing. Furthermore, its clinical feature is reported to be gradually changing. However, few reports to clarify the current features of pNTM have been published. The aim of this study is to investigate microbiological and clinical features of pNTM. PATIENTS AND METHODS: This study was a retrospective observational study. Patients with pNTM visited to Dokkyo Medical University Koshigaya Hospital between January 2009 and December 2010 were enrolled. All patients fulfilled the diagnostic criteria in Japanese guidelines for nontuberculous mycobacterial pulmonary disease published in 2008. Medical records were reviewed to obtain information about the enrolled patients. RESULTS: Total 143 patients (49 males and 94 females, age 67 +/- 10 yrs) were enrolled in this study. Only 11.9% of patients had malignant diseases and 5.6% had diabetes mellitus whereas 79% had no comorbidity. Nearly 60% of patients showed normal BMI. At the time of diagnosis, 52.0% of patients had no symptom whereas 22.3% had cough and/or sputum, and 7.1% had hemoptysis. The results of smear examination with acid-fast staining were negative in 80.4%, +/- in 9.8%, 1 + in 7.7% and 2 + in 2.1%. Causative pathogens detected with acid-fast bacillus culture were Mycobacterium avium (M. avium) (74.8%), M. intracellulare (14.0%), M. fortuitum (3.5%), M. abscessus (2.8%), M. kansasii (2.8%) and others. CONCLUSION: This study showed that majority of patients had no symptoms and/or negative results of smear examination with acid-fast staining. It is crucial to consider these facts when a diagnostic test of pNTM is performed. PMID- 24218764 TI - [An autopsy case of B lymphoblastic leukemia/lymphoma with hemophagocytic syndrome infiltrating in the central nervous systems]. AB - The hemophagocytic syndrome(HPS) after the hematopoietic stem cell transplantation(SHCT) may be triggered by the reactivation of virus such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV) under immunosuppressive state. The present case was a 17-year old man who was diagnosed as B lymphoblastic leukemia. Bone marrow aspiration showed 96.4% of lymphoblasts with positive for CD19 and CD20, negative for CD66 and POX, and dot staining for PAS. E2A/PBX1 chimeric mRNA was positive as assessed by RT-PCR method. He received three courses of induction chemotherapy followed by allo-bone marrow transplantation (BMT) from his sister, but had a relapse three months after allo-BMT. He received allo peripheral blood-SCT (PBSCT) from his mother. The hematopoietic cells successfully engrafted, but the mixed chimerism of 2 donors persisted. On day 149, he had a fever, and hemophagocytosis was found by bone marrow aspiration. EBV genomic DNA was detected for 1.62 x 10(3) copies. CMV and fungus were negative in blood. On day 165, the patient had been observed disturbance of consciousness, neck stiffness, and died on day 170 due to multiple organ failure. Autopsy examination showed infiltration of CD20+ leukemic cells into the perivascular space of cerebrum, brainstem and spinal cord, with hemophagocytosis by CD6+ macrophages. In situ hybridization of EB-virus encoded small RNA (EBER) confirmed EBV infection of B-lymphoblastic cells infiltrated in the cerebrum. HPS was considered to be triggered by the reactivation of EBV, due to hematopoietic dysfunction based on long-term immunosuppressive treatment and mixed chimerism derived from a HSCT from 2 donors. PMID- 24218765 TI - [Future roles of clinical laboratories and clinical laboratory technologists in university hospitals]. AB - Clinical laboratories in university hospitals should be operated with a good balance of medical practice, education, research, and management. The role of a clinical laboratory is to promptly provide highly reliable laboratory data to satisfy the needs of clinicians involved in medical practice and health maintenance of patients. Improvement and maintenance of the quality of the laboratory staff and environment are essential to achieve this goal. In order to implement these requirements efficiently, an appropriate quality management system should be introduced and established, and evaluated objectively by a third party (e.g. by obtaining ISO 15189 certification). ISO 15189 is an international standard regarding the quality and competence of clinical laboratories, and specifies a review of the efficient operational system and technical requirements such as competence in implementing practical tests and calibration. This means the results of laboratory tests reported by accredited laboratories withstand any international evaluation, which is very important to assure the future importance of the existence and management of clinical laboratories as well as internationalization of medical practice. "Education" and "research" have important implications in addition to "medical practice" and "management", as the roles that clinical laboratories should play in university hospitals. University hospital laboratories should be operated by keeping these four factors in good balance. Why are "education" and "research" required in addition to "medical practice" services? If individual clinical laboratory technologists can provide an appropriate response to this question, the importance of the existence of clinical laboratories would be reinforced, without being compromised. PMID- 24218766 TI - [Potential and perspective of genetic testing in Renaissance of laboratory medicine]. AB - Among molecular genetic tests, tests for genomic biomarkers are increasingly performed in order to decide the right drug for the right patient at the right time. These genetic tests, including pharmacogenomics (PGx) tests, are essential for personalized medicine. Companion diagnostics (CDx) will be co-developed from the early stage of drug development and used for patient stratification in Phases II/III of clinical trials. The strategic change in development from blockbuster drugs to molecularly targeted drugs will enhance the clinical application of genetic tests, including CDx and PGx. The genetic tests utilized for making treatment decisions have the potential to regenerate laboratory medicine. PMID- 24218767 TI - [Multi-drug resistant organisms are important issues in preventing healthcare associated infections. Introduction]. AB - Multi-drug-resistant organisms are important issues in preventing healthcare associated infections (HAIs); however, severe infection control in a hospital or healthcare facility cannot reduce HAIs. A surveillance system to detect multi drug-resistant organisms is necessary in a prefecture or broader area including many healthcare facilities. The Ministry of Health, Labor and Welfare of Japan proposed to survey HAIs and multi-drug-resistant organisms in a region, and supported this surveillance by newly adding insurance points for regional infection control; however, definite actions were not presented and various trials have been attempted. In this symposium, several trials to survey multi drug-resistant organisms in various regions were presented, and we searched for clues to prevent multi-drug-resistant organism infection. PMID- 24218768 TI - [Surveillance system for multidrug-resistant bacteria in Nagano Prefecture]. AB - Surveillance for vancomycin-resistant Enterococcus species and multidrug resistant Pseudomonas aeruginosa started in 2007 in Nagano prefecture. Moreover, we have been able to survey almost all multidrug-resistant bacteria using the Shinshu infection control surveillance system (SICSS) since 2011, and check for outbreaks of multidrug-resistant bacteria throughout Nagano prefecture in real time, as happened in a hospital. Using the SICSS, we can prevent pathogens from spreading from a hospital to neighboring hospitals, and support facilities without a specialist in infection control. A surveillance system such as the SICSS is fundamental for regional infection control. PMID- 24218769 TI - [Importance of and problems in sharing surveillance data of antimicrobial susceptibility among hospitals in Oita Prefecture]. AB - The treatment and prevention of antimicrobial resistant bacterial infections are critical in the management and maintenance of high-quality clinical health services. Surveillance of antimicrobial resistant bacteria is a useful tool for controlling resistant pathogens. In order to prevent the spread of antimicrobial resistant pathogens in a region, surveillance data should be shared among the hospitals in the same area. In Oita Prefecture, 17 hospitals share antimicrobial resistant bacteria surveillance data. The collected data of the 17 hospitals is valuable in determining the isolation rate of antimicrobial resistant bacteria, such as MRSA, MDRP, and MDRA which are important for hospital acquired infections. This information also provides beneficial knowledge for empiric therapy against infectious diseases. However, further efforts are necessary in sharing the surveillance data among hospitals and collecting more detailed data. It is very important for the hospitals to agree on purpose of sharing the antimicrobial resistant bacterial surveillance data. PMID- 24218770 TI - [Laboratory-based surveillance of antibacterial drug-resistant bacteria in the Kinki region]. AB - The study of bacterial resistance in the Kinki region of Japan (SBRK) was launched in 1997 for the purpose of monitoring antibacterial drug-resistant bacteria. In SBRK, laboratory-based surveillance, such as of Streptococcus pneumonia, Haemophillus influenzae, extended spectrum beta-lactamase-producing Enterobacteriaceae, carbapenemase producing Gram-negative rods, etc. has been carried out for over 10 years and the results have been reported through seminars and conference presentations. Technical seminars of detection methods for clinically important drug-resistant bacteria were also held in order to contribute to improving the quality of microbiology laboratories. To conduct appropriate infection control of drug-resistant bacteria, effective utilization of quality-assured microbiological data and information sharing of regional epidemiological data is very important. The construction of regional cooperation systems among microbiology laboratories and with public institutions is strongly required. PMID- 24218771 TI - [Role of university hospitals in regional infection control network]. AB - Activities and the understanding of infection control in healthcare facilities have improved in the past decade since a certification system for medical personnel, such as infection control nurse and infection control doctor, were introduced in Japan. These specialists are distributed among tertiary general hospitals, while many small and mid-scale hospitals have no infection control specialists. In 2012, the Japanese Ministry of Health, Labour and Welfare launched a new strategy for further improvement of infection control by supporting a regional network of infection control activities. Through the infection control network, small or mid-scaled hospitals can utilize infection control specialists in tertiary general hospitals, enter educational programs on infection control and consult in cases of nosocomial infection outbreaks. As part of the regional infection control network, we established an information network system, named ReNICS, to share the bacteriological test results of the hospitals in Akita prefecture. ReNICS offers epidemiological data on bacteria identified in the region. We can identify the spread of multi-drug resistant bacteria and can roughly estimate the quality of infection control activities in each facility. As a similar information network is being prepared in Hirosaki University Hospital Infection Control Center in Aomori, a prefecture neighboring Akita, we discussed the roles of university hospitals for a regional infection control network. PMID- 24218772 TI - [Can you detect organisms and diagnose bacterial infections from microscopic examinations?]. AB - The Gram stain is an important diagnostic examination for infectious disease. It classifies four patterns of morphology. In particular, a sputum Gram stain can identify infectious organisms and adequate antimicrobial therapy. We also observe fibrin and polynuclear leucocytes in specimens under a microscope to help diagnosis and therapy. PMID- 24218773 TI - [Countermeasures against patient misidentification in laboratory study- chairmen's introductory remarks]. AB - Since the launch of the "National Joint Action of Risk Management" back in May, 2008, as a participating organization, The Japanese Society of Laboratory Medicine has been running a Medical Safety Committee of our own. As part of our awareness education activities, our society has been holding symposia on medical safety at our annual meetings. In clinical practice, misidentification of patients is directly connected to serious medical mistakes. Although clinical practice itself must be safe for all, the actual clinical setting poses many hazards that could lead to medical professionals making errors. Since misidentification of patients regarding obtained specimens such as blood or physical function exams and misinterpretation of the exams itself can result in a serious outcome, every institute is using ingenious ways to keep close checks to prevent such misidentifications from happening. In this symposium, lectures were presented in the following subjects: A review on countermeasures against specimen misidentification in pathological exams in hospitals using electronic patient verification systems to prevent misidentification of patient blood samples, and hospitals where such systems are not employed; an introduction of countermeasures against specimen misidentification in pathological exams; and lastly, characteristics and limitations of human abilities, and process management, entitled "Human Factor Approaches to Medical Safety". PMID- 24218774 TI - [Counter-measures against patient misidentification and specimen mismanagement with blood collection]. AB - My theme for this symposium is counter-measures against patient misidentification and specimen mismanagement with blood collection due to the lack of using authentication systems. What is applicable to our laboratory is patient misidentification counter-measures for specimen management at the time of inpatient ward blood collection and specimen examination (mistakes in appending bar code labels and entering specimen numbers). During the period from January 2008 to July 2012 at our laboratory, there were 9 cases of patient misidentification for hospital ward blood collection and specimen management. There were 2 cases in 2008 (1 for blood collection, 1 for specimen management), no cases in 2009, 3 cases in 2010 involving blood collection, 1 case in 2011 involving specimen management, and 3 cases in 2012 (1 for blood collection, 2 for specimen management). All patient misidentifications involving hospital ward blood collection arose from bedside blood collection. As a counter-measure, training slides were created at a medical safety management review session, repeated training in attention and patient check procedures was conducted with staff members, and hands-on training in pointing and naming was carried out. With these training slides, the goal was the execution of verification duties by encouraging conversations that include the patient's name, such as "Mr./Ms. XXXX, today we'll be collecting 3 tubes of blood," as a link to patient verification duties. With specimen management, 3 of the 4 cases occurred during overtime for day-shift work. As counter measures: 1) adherence to 1 patient, 1 tray, and signing when matching; 2) as a counter-measure against mistaking specimens for blood gas hemolysis, confirmation as other specimens, separating approximately 3 drops of blood that cannot be used for sampling, confirming hemolysis, and preventing misidentification. PMID- 24218775 TI - [Measures to prevent patient identification errors in blood collection/physiological function testing utilizing a laboratory information system]. AB - We constructed an integrated personal identification workflow chart using both bar code reading and an all in-one laboratory information system. The information system not only handles test data but also the information needed for patient guidance in the laboratory department. The reception terminals at the entrance, displays for patient guidance and patient identification tools at blood-sampling booths are all controlled by the information system. The number of patient identification errors was greatly reduced by the system. However, identification errors have not been abolished in the ultrasound department. After re-evaluation of the patient identification process in this department, we recognized that the major reason for the errors came from excessive identification workflow. Ordinarily, an ultrasound test requires patient identification 3 times, because 3 different systems are required during the entire test process, i.e. ultrasound modality system, laboratory information system and a system for producing reports. We are trying to connect the 3 different systems to develop a one-time identification workflow, but it is not a simple task and has not been completed yet. Utilization of the laboratory information system is effective, but is not yet perfect for patient identification. The most fundamental procedure for patient identification is to ask a person's name even today. Everyday checks in the ordinary workflow and everyone's participation in safety-management activity are important for the prevention of patient identification errors. PMID- 24218776 TI - [Specimen misidentification in pathology laboratory: trends and measures]. AB - Specimen misidentification in pathology laboratories may have serious consequences. Reports on the frequency of errors in pathology laboratories in Japan are rare. We reviewed near-miss and incident reports over 7 years in our laboratory, extracted those associated with misidentification, analyzed annual changes in numbers and content, and discussed the problems faced and measures taken to prevent misidentification. Of 113,447 pathological cases, 88 (0.078%) reports were associated with misidentification. Of these 88 misidentification cases, 19% occurred before and during accessioning, 16% during dissecting and sectioning, 30% during embedding, 13% during tissue cutting and slide mounting, 19% during slide submitting, and 3% during diagnosis. Two cases (2.3%) of misidentification were detected after diagnosis; however, misidentification did not appear to cause adverse effects in any patient. The frequency of events is similar to that reported in the literature; specimen misidentification was noted in 0.1-0.2% of cases in a modern pathology laboratory. Two-thirds of misidentification events occurred associated with gross specimens, similar to findings in other studies. With the introduction of new technologies that minimize the possibility of human errors (e.g., barcode reading, digital imaging of every specimen, and installation of a glass slide printer), education on medical safety, and the use of multiple safety nets (e.g., diagnosis cancelling and slide checking), errors have decreased, but have not been eliminated completely. Recording errors and reporting them to the hospital and social community, and maintaining a sustainable quality improvement system is very important to reduce errors in pathology. PMID- 24218777 TI - Stillbirth and the law: options for law reform and issues for the coronial jurisdiction. AB - In spite of its relative frequency, stillbirth is a phenomenon that has been relatively little discussed and requires further research for comprehensive clinical understanding. It impacts upon the legal system by way of the need to determine whether a life has come into being such that legal consequences such as criminal law, probate law and the coronial jurisdiction can attach to it. This requires contemporary clinically informed interpretation and application of the ancient "born alive rule" in respect of the ramifications of matters such as pulseless electrical activity in the heart, brain activity and agonal gasping. In the coronial domain, arguments have been put in South Australia, Victoria and Northern Ireland in recent cases and discussion has taken place publicly about whether coroners should be permitted to investigate and make findings and recommendations about cases of stillbirth. The article identifies merit in principle in such a development but highlights the need for care about such reform to the law lest it engender inconsistency in respect of important threshold definitions of "life" and "death" lest it generate incoherent approaches of the law on the subject, and lest it have unforeseen counter therapeutic consequences for the grieving parents of infants who have been stillborn. It notes, too, that such a change to the ambit of coronial jurisdiction would have important resourcing ramifications. PMID- 24218778 TI - Opioid regulation: time to reconsider the nomenclature and approach. AB - In Australia, deaths due to the ingestion of opioid analgesics, though numerically small, have been increasing at a rapid rate. The reasons for this increase are multifactorial; the conceptually outdated legislation that controls prescription and administration of opioid analgesics might be one of them. The stated purposes of the governing statutory instruments include prevention of the improper use of drugs of dependence and protection of the public. However, in order to achieve these aims, the relevant legislation should utilise theories and definitions that are consistent with the medical understanding of the relevant physiology and behaviour, so as to provide a common linguistic and conceptual platform for regulatory and clinical decision-makers. Although Victoria, with its intricate statutory framework for Schedule 8 poisons, is used as an example of an obsolescent approach to the concept of drug dependency, conclusions reached are applicable to other jurisdictions, other scheduled drugs, and all health care practitioners who have the statutory authority to possess and prescribe them. PMID- 24218779 TI - Disorders, sublime menu: the DSM-5. AB - The release of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is the culmination of a long and remarkably public discussion which was accompanied by a great deal of controversy. Diagnostic criteria for many disorders have changed, the structure of the DSM is different, and there remain significant concerns about the forensic application of the DSM. This column briefly covers the primary changes and summarises the debate about various diagnoses, with a particular focus on diagnoses of relevance to medico-legal psychiatry and the legal system. Underlying concerns about the validity of diagnostic criteria and their applicability to forensic issues are discussed. Concerns about the DSM-5 are not only due to the specific diagnoses and their criteria, but the methodology of checklist criteria. This is amplified in medico legal settings, but is also in part necessary. Clinicians, lawyers, and judges will all need to think carefully about how they use the DSM and its ilk in forensic settings. PMID- 24218780 TI - Double standards in special medical research: questioning the discrepancy between requirements for medical research involving incompetent adults and medical research involving children. AB - Medical research represents a substantial departure from conventional medical care. Medical care is patient-orientated, with decisions based on the best interests and/or wishes of the person receiving the care. In contrast, medical research is future-directed. Primarily it aims to contribute new knowledge about illness or disease, or new knowledge about interventions, such as drugs, that impact upon some human condition. Current State and Territory laws and research ethics guidelines in Australia relating to the review of medical research appropriately acknowledge that the functions of medical care and medical research differ. Prior to a medical research project commencing, the study must be reviewed and approved by a Human Research Ethics Committee (HREC). For medical research involving incompetent adults, some jurisdictions require an additional, independent safeguard by way of tribunal or court approval of medical research protocols. This extra review process reflects the uncertainty of medical research involvement, and the difficulties surrogate decision-makers of incompetent adults face in making decisions about others, and deliberating about the risks and benefits of research involvement. Parents of children also face the same difficulties when making decisions about their child's research involvement. However, unlike the position concerning incompetent adults, there are no similar safeguards under Australian law in relation to the approval of medical research involving children. This column questions why this discrepancy exists with a view to generating further dialogue on the topic. PMID- 24218782 TI - Death scene evaluation in hoarding disorders--Diogenes syndrome. PMID- 24218781 TI - Disclosure of material risk as systems-error tragedy: Wallace v Kam (2013) 87 ALJR 648; [2013] HCA 19. AB - The law requiring a patient to be informed not just of the nature of a medical procedure but also its likely but subjectively significant risks, which blazed across the southerly firmament of patients' rights in 1992 with the decision of Rogers v Whitaker (1992) 175 CLR 479, appears to have now passed to the outer darkness of judicial deference. The decision of the Australian High Court in Wallace v Kam (2013) 87 ALJR 648; [2013] HCA 19 continues the judicial trend to go cool on patients' rights and restrict the capacity of medically injured people to claim redress which was evident in Rosenberg v Percival (2001) 205 CLR 434 and various Australian State civil claims statutes. This trend only heightens the analogy between the law of informed consent and classical literary tragedy. Indeed, heightening the analogy between the legislation and case law on disclosure of material risk and classical literary tragedy may provide necessary insights to bring greater justice to patients injured as a result of medical misadventure and incompetence. PMID- 24218783 TI - Determining the risk of recidivism in previously de-registered health practitioners. AB - Health practitioners who have been de-registered in the past due to serious professional misconduct pose significant challenges to registration boards and tribunals when applying for re-registration. These practitioners need to demonstrate to their professional regulatory body that they possess the necessary attributes expected of a member of a caring profession. Boards are obliged by legislation to decline to grant registration to any applicant if that person is deemed not fit and proper to be a member of the profession or who poses a risk to public safety. Studies have shown a significant incidence of repeated misconduct among previously de-registered practitioners and the exercise of re-registration requires an accurate assessment of this risk of recidivism. This article examines the incidence and risk of recidivism in previously de-registered health practitioners. It also discusses how boards may more accurately perform an assessment of the risk and thereby assist them to meet their statutory obligation of public protection. PMID- 24218784 TI - Is whistleblowing now mandatory? The impact of mandatory reporting law on trust relationships in health care. AB - Trust is vital for promoting positive health care relationships aimed at achieving positive patient outcomes. Patients, as well as the broader society, trust that health care practitioners who have been granted authority by the state to provide safe and beneficial health care are competent to do so. Recent instances where patients have been harmed as the result of treatment that fell below the accepted standard of competence have negatively impacted on trust. As the state has a responsibility to protect the public from this type of harm, legislation that mandates reporting of certain instances where the behaviour of health care professionals has fallen below the acceptable standard has been introduced. While this may have been designed to restore public trust, this article argues that it has the potential to diminish trust on the basis that mandatory reporting may be equivalent to mandatory whistleblowing. PMID- 24218785 TI - A curious exception: (no) legal remedies for negligent pre-birth genetic testing. AB - This article analyses the ability of parents and resulting children to claim compensation for negligent pre-birth genetic testing in New Zealand. It looks first at whether the parents and/or the child can claim compensation under New Zealand's statutory compensation scheme. It then assesses whether there are any remedies in tort, namely the torts of wrongful birth or wrongful life, that the parents or the child could use. It concludes that, at present, there is no legal ability for either the parents or the child to obtain compensation for negligent pre-birth genetic testing in New Zealand. PMID- 24218786 TI - Work-related musculoskeletal injury and suicide: opportunities for intervention and therapeutic jurisprudence. AB - This article presents evidence for the existence of a common trajectory from work related musculoskeletal injury to suicide. Specifically, it is argued that the pathway from injury to suicide is typically mediated by three critical events: unsuccessful return to work; the development of chronic pain or disability; and suicidal ideation in the context of chronic pain. The moderating influence of systemic factors is also examined, along with opportunities for intervention at the individual and systemic levels, the latter arising from a therapeutic jurisprudence perspective. PMID- 24218787 TI - Children and refusal of medical treatment: in urgent need of reform. AB - The ability of children to refuse medical treatment is far from certain. The New South Wales Law Reform Commission report on this topic, released in 2008, addressed a number of key concerns. As yet, no action on that report has been taken. Neither the present statutory nor common law regime provides sufficient guidance on this issue. The case of Gillick v West Norfolk and Wisbech Area Health Authority [1986] AC 112, while important, is not as far-reaching as it first appeared and has been subject to substantial limitations regarding refusals of treatment. Specifically, the position in relation to the assessment of competency, and the weight of a competent decision, remains outstanding. The ability of children to refuse medical treatment is in urgent need of attention and rectification. PMID- 24218788 TI - A minority report: homebirth in Australia before and after the 2009 Maternity Services Review. AB - In 2009 the Australian Federal Government released its Maternity Services Review. Since then, homebirth has been virtually outlawed for those women who are unable to obtain one of the limited places on a publicly funded program. However, homebirth is a valid choice for women and advocating for homebirth does not reflect a desire to "turn back the clock", as regard to the history of birth will show. At its core, the controversy over homebirth is about the control of pregnant women's bodies, particularly when they make a choice about their bodies and their babies which sits outside of the mainstream. While only a minority of Australian women presently plan a homebirth, the issues surrounding the status of homebirth have wider implications for women and illustrate a troubling trend towards restricting choice through legal and administrative back-roads, without proper consideration of the risks or benefits involved. PMID- 24218789 TI - Jabs and barbs: ways to address misleading vaccination and immunisation information using currently available strategies. AB - Misleading vaccination information undermines confidence in vaccination and may lead to reductions in the effectiveness of vaccination programs. A number of regulatory techniques can be employed to challenge the spread of false information, including health care complaints, therapeutic goods laws, consumer protection laws and professional discipline. This article examines three case studies involving the publication of anti-vaccination information by non professionally aligned organisations, by non-registered health professionals, and by registered health professionals under the National Law. The article examines the effectiveness of different regulatory responses and makes suggestions for future strategies to deal with the publication of demonstrably false information regarding vaccination. PMID- 24218790 TI - Medical malpractice and the professional legal responsibility of the sports physician. AB - As with other medical specialties, litigation in sports medicine appears to be on the increase. In most countries, the applicable legal standard is "good medical practice" as identified with reference to the physician's own field of specialisation: what is commonly done by physicians in the same specialty generally serves as the standard by which a physician's conduct is measured. To enhance the quality of sports medicine practice, medical societies have been issuing guidelines for use by sports physicians, and a number of courts have recognised guidelines as evidence of good medical practice. One potential field of malpractice in sports medicine relates to privacy issues: an athlete should be asked to fill in a consent form if the medical information needs to be shared with other parties. Another relevant field is doping: for any act of drug prescription to be legally sound, sports physicians have to be aware of the requirements of the World Anti-Doping Agency Code and its international standards. Ultimately, the best way for sports physicians to avoid sources of liability is for them to keep up to date with the latest research and to act in a careful and diligent manner. PMID- 24218791 TI - Rights and research: an examination of research under New Zealand's Code of Health and Disability Services Consumers' Rights. AB - New Zealand's Code of Health and Disability Services Consumers'Rights came into force in 1996 after Judge Silva Cartwright's Cervical Cancer Inquiry concluded that a research study into the course of cervical cancer had taken place at National Women's Hospital without the participants' knowledge or consent. The Code creates rights in respect of the provision of health and disability services which explicitly extend to research. However, in the absence of a statutory definition of "research", its meaning and the application of the Code to research in New Zealand are unclear. This article seeks to identify the gaps and find a solution. PMID- 24218792 TI - The international right to health: state obligations and private actors in the health care system. AB - Most health systems have historically used a mix of public and private actors for financing and delivering care. But the last 30 years have seen many rich and middle-income countries moving to privatise parts of their health care systems. This phenomenon has generated concerns, especially about equitable access to health care. This article examines what the international right to the highest attainable standard of health in Art 12 of the International Covenant on Economic, Social and Cultural Rights says about the obligations of states which use private actors in health care. The article involves a close study of the primary documents of the key institutions responsible for interpreting and promoting Art 12. From this study, the article concludes that in mixed public private health care systems, states not only retain primary responsibility for fulfilling the right to health but are subject to a range of additional specific responsibilities. PMID- 24218793 TI - Scoping the ethics of dementia research within an Australian human research context. AB - Research with people with dementia can be ethically challenging because of the effects of dementia on cognitive function. A narrative literature review of ethical human dementia research was conducted, highlighting ethical challenges that can be categorised under the following themes: substitute judgment; how capacity can vary due to risks; barriers to recruiting people with dementia; how to determine capacity to give consent; and gaining assent rather than consent from participants. The results of the review were further analysed in relation to the Australian National Statement on Ethical Conduct in Human Research (National Statement). Gaps in the National Statement include: how capacity should be determined; what defines best interests; how assent and dissent by someone with dementia should be determined and respected; and whether or not people with dementia should be included in high-risk research. PMID- 24218794 TI - Australian reforms enabling disclosure of genetic information to genetic relatives by health practitioners. AB - The familial nature of genetic information means that information about one family member may have relevance for the health of genetic relatives; however, patients are not always willing to share relevant information. This article outlines groundbreaking legislative developments in Australia which create a lawful pathway for health practitioners to make disclosure of genetic information to genetic relatives notwithstanding refusal by the patient to consent to such disclosure. The article traces the background to this reform, and its implementation through amendments to the Privacy Act 1988 (Cth) and the introduction of enabling guidelines. It examines the circumstances in which disclosure is permitted and the protocols established under guidelines and the strengths and limitations of these reforms. Pursuant to these changes, health practitioners are not legally obliged to make disclosure but are legally able to do so without breaching statutory privacy obligations. The aim is to encourage this as best practice in appropriate circumstances but questions remain regarding the interplay between ethics and law if disclosure is indicated but not made with adverse health consequences for the relatives. PMID- 24218795 TI - [A very special woman]. PMID- 24218796 TI - [On the 80th birthday of Sister Liliane Juchli. Impressive, touching and highly motivating]. PMID- 24218797 TI - [Work qualifications: family friendliness as an advantage in recruitment]. PMID- 24218798 TI - [Advanced nursing practice in England: bridge between medicine and nursing]. PMID- 24218799 TI - [Yvonne Ribi: "It is about more than benefits" (interview by Urs Luthi)]. PMID- 24218800 TI - [Swiss DRG: CHOP codes for complex nursing treatment. Nursing finds entry into DRG]. PMID- 24218801 TI - [Wound care: a collaboration as in an orchestra]. PMID- 24218802 TI - [Telephone counseling with simulated patients: "How can I support you?"]. PMID- 24218803 TI - [Annatina Jackle. "I have learned to be tolerant" (interview by Urs Luthi)]. PMID- 24218804 TI - [Everything on the table]. PMID- 24218805 TI - ["When the past no longer illuminates the future, the spirit walks in darkness"]. PMID- 24218806 TI - [Digital medicine and e-health: the future starts today]. PMID- 24218807 TI - [Needs of patients with fibromyalgia and needs of caregivers facing this disease: defining the nurse's role]. PMID- 24218808 TI - [Recognizing the efforts of positive treatment: the Sonate label]. PMID- 24218810 TI - [Return to the events of Providence: faithful to the ASI but outraged]. PMID- 24218809 TI - [The nursing instructor: a "guide for the pathway"]. PMID- 24218811 TI - [The Atlasprofilax method: giving back to the atlas its natural place]. PMID- 24218813 TI - Continuous live cell imaging of cellulose attachment by microbes under anaerobic and thermophilic conditions using confocal microscopy. AB - Live cell imaging methods provide important insights into the dynamics of cellular processes that cannot be derived easily from population-averaged datasets. In the bioenergy field, much research is focused on fermentation of cellulosic biomass by thermophilic microbes to produce biofuels; however, little effort is dedicated to the development of imaging tools to monitor this dynamic biological process. This is, in part, due to the experimental challenges of imaging cells under both anaerobic and thermophilic conditions. Here an imaging system is described that integrates confocal microscopy, a flow cell device, and a lipophilic dye to visualize cells. Solutions to technical obstacles regarding suitable fluorescent markers, photodamage during imaging, and maintenance of environmental conditions during imaging are presented. This system was utilized to observe cellulose colonization by Clostridium thermocellum under anaerobic conditions at 60 degrees C. This method enables live cell imaging of bacterial growth under anaerobic and thermophilic conditions and should be widely applicable to visualizing different cell types or processes in real time. PMID- 24218814 TI - Response of anaerobes to methyl fluoride, 2-bromoethanesulfonate and hydrogen during acetate degradation. AB - To use the selective inhibition method for quantitative analysis of acetate metabolism in methanogenic systems, the responses of microbial communities and metabolic activities, which were involved in anaerobic degradation of acetate, to the addition of methyl fluoride (CH3F), 2-bromoethanesulfonate (BES) and hydrogen were investigated in a thermophilic batch experiment. Both the methanogenic inhibitors, i.e., CH3F and BES, showed their effectiveness on inhibiting CH4 production, whereas acetate metabolism other than acetoclastic methanogenesis was stimulated by BES, as reflected by the fluctuated acetate concentration. Syntrophic acetate oxidation was thermodynamically blocked by hydrogen (H2), while H2-utilizing reactions as hydrogenotrophic methanogenesis and homoacetogenesis were correspondingly promoted. Results of PCR-DGGE fingerprinting showed that, CH3F did not influence the microbial populations significantly. However, the BES and hydrogen notably altered the bacterial community structures and increased the diversity. BES gradually changed the methanogenic community structure by affecting the existence of different populations to different levels, whilst H2 greatly changed the abundance of different methanogenic populations, and induced growth of new species. PMID- 24218815 TI - Effect of airflow on biodrying of gardening wastes in reactors. AB - Biodrying consists of reducing moisture by using the heat from aerobic bio degradation. The parameters that control the process are: aeration, temperature during the process, initial moisture of biowaste, and temperature and relative humidity of the input air. Lawn mowing and garden waste from the gardens of the University Jaume I, Castellon (Spain) were used as a substrate. Biodrying was performed in 10 reactors with known air volumes from 0.88 to 6.42 L/(min x kg dry weight). To promote aeration, 5 of the reactors had 15% of a bulking agent added. The experiment lasted 20 days. After the experiments it was found that the bulking agent led to greater weight loss. However, the increased airflow rate was not linearly proportional to the weight loss. PMID- 24218816 TI - The ex vivo and in vivo biological performances of graphene oxide and the impact of surfactant on graphene oxide's biocompatibility. AB - Graphene oxide (GO) displays promising properties for biomedical applications including drug delivery and cancer therapeutics. However, GO exposure also raises safety concerns such as potential side effects on health. Here, the biological effects of GO suspended in phosphate buffered saline (PBS) with or without 1% nonionic surfactant Tween 80 were investigated. Based on the ex vivo experiments, Tween 80 significantly affected the interaction between GO and peripheral blood from mice. GO suspension in PBS tended to provoke the aggregation of diluted blood cells, which could be prevented by the addition of Tween 80. After intravenous administration, GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system. Nevertheless, GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80. In contrast, less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension. Organs including hearts, livers, lungs, spleens, kidneys, brains, and testes did not reveal histological alterations. The indexes of peripheral blood showed no change upon GO exposure. Our results together demonstrated that Tween 80 could greatly alter GO's biological performance and determine the pattern of its biodistribution in mice. PMID- 24218817 TI - Determination of the mechanism of photoinduced toxicity of selected metal oxide nanoparticles (ZnO, CuO, Co3O4 and TiO2) to E. coli bacteria. AB - Cytotoxicity of selected metal oxide nanoparticles (MNPs) (ZnO, CuO, Co3O4 and TiO2) was investigated in Escherichia coli both under light and dark conditions. Cytotoxicity experiments were conducted with spread plate counting and the LC50 values were calculated. We determined the mechanism of toxicity via measurements of oxidative stress, reduced glutathione, lipid peroxidation, and metal ions. The overall ranking of the LC50 values was in the order of ZnO < CuO < Co3O4 < TiO2 under dark condition and ZnO < CuO < TiO2 < Co3O4 under light condition. ZnO MNPs were the most toxic among the tested nanoparticles. Our results indicate depletion of reduced glutathione level and elevation of malondialdehyde level correlated with the increase in oxidative stress. Released metal ions were found to have partial effect on the toxicity of MNPs to E. coli. In summary, the dynamic interactions of multiple mechanisms lead to the toxicity of the tested MNPs to E. coli. PMID- 24218818 TI - Joint effects of heavy metal binary mixtures on seed germination, root and shoot growth, bacterial bioluminescence, and gene mutation. AB - This investigation was to assess the joint effects of metal binary mixtures on seed germination, root and shoot growth, bacterial bioluminescence, and gene mutation based on the one toxic unit (1 TU) approach. Different sensitivities and orders of toxicity of metal mixtures were observed among the bioassays. In general, mostly additive or antagonistic effects were observed, while almost no synergistic effects by the binary metal mixtures in all bioassays. Therefore, the combined effects of heavy metals in the different bioassays were difficult to generalize since they were dependent on both chemical type and the organism used in each bioassay. However, these results indicate that a battery of bioassays with mixture chemicals as opposed to just a single assay with single metal is a better strategy for the bioassessment of environmental pollutants. PMID- 24218819 TI - An online monitoring system for atmospheric nitrous acid (HONO) based on stripping coil and ion chromatography. AB - A new instrument for measuring atmospheric nitrous acid (HONO) was developed, consisting of a double-wall glass stripping coil sampler coupled with ion chromatography (SC-IC). SC-IC is featured by small size (50 x 35 x 25 cm) and modular construction, including three independent parts: the sampling unit, the transfer and supporting unit, and the detection unit. High collection efficiency (> 99%) was achieved with 25 micromol/L Na2CO3 as absorption solution even in the presence of highly acidic compounds. This instrument has a detection limit of 8 pptv at 15 min time resolution, with a measurement uncertainty of 7%. Potential interferences from NO(x), NO2+SO2, NO2+VOCs, HONO+O3, HNO3, peroxyacetyl nitrite (PAN) and particle nitrite were quantified in laboratory studies and were found to be insignificant under typical atmospheric conditions. Within the framework of the 3C-STAR project, inter-comparison between the SC-IC and LOPAP (long path liquid absorption photometer) was conducted at a rural site in the Pearl River Delta. Good agreement was achieved between the two instruments over three weeks. Both instruments determined a clear diurnal profile of ambient HONO concentrations from 0.1 to 2.5 ppbv. However, deviations were found for low ambient HONO concentrations (i.e. < 0.3 ppbv), which cannot be explained by previous investigated interference species. To accurately determine the HONO budget under illuminated conditions, more intercomparison of HONO measurement techniques is still needed in future studies, especially at low HONO concentrations. PMID- 24218820 TI - Formaldehyde concentration and its influencing factors in residential homes after decoration at Hangzhou, China. AB - Air pollution surveys of formaldehyde (HCHO) were conducted in 2324 rooms decorated within one year in 2007-2009 in Hangzhou, China. The mean HCHO concentration (CHCHO) was 0.107 +/- 0.095 mg/m3, and 38.9% of samples exceeded the Chinese National Standard GB 50325-2010. Over the past 3 years, the C(HCHO) decreased with time (p < 0.05). Relationships of potential factors to indoor C(HCHO) were also evaluated. C(HCHO) was related to temperature (T), relative humidity (RH), time duration of the windows and doors being closed before sampling (DC), time duration from the end of decoration to sampling (DR) and source characteristics (d). A model to relate indoor C(HCHO) to these five factors (T, RH, DC, DR, d) was established based on 298 samples (R2 = 0.87). Various factors contributed to C(HCHO) in the following order: T, 43.7%; d, 31.0%; DC, 10.2%; DR, 8.0%; RH, 7.0%; specifically, meteorological conditions (i.e., RH plus T) accounted for 50.7%. The coefficient of T and RH, R(TH), was proposed to describe their combined influence on HCHO emission, which also had a linear relationship (R2 = 0.9387) with HCHO release in a simulation chamber test. In addition, experiments confirm that it is a synergistic action as T and RH accelerate the release of HCHO, and that is a significant factor influencing indoor HCHO pollution. These achievements could lead to reference values of measures for the efficient reduction of indoor HCHO pollution. PMID- 24218821 TI - Flocculating characteristic of activated sludge flocs: interaction between Al(3+)) and extracellular polymeric substances. AB - Aluminum flocculant can enhance the flocculating performance of activated sludge. However, the binding mechanism of aluminum ion (Al(3+)) and extracellular polymeric substances (EPS) in activated sludge is unclear due to the complexity of EPS. In this work, three-dimensional excitation emission matrix fluorescence spectroscopy (3DEEM), fluorescence quenching titration and Fourier transform infrared spectroscopy (FT-IR) were used to explore the binding behavior and mechanism between Al(3+) and EPS. The results showed that two fluorescence peaks of tyrosine- and tryptophan-like substances were identified in the loosely bound extracellular polymeric substances (LB-EPS), and three peaks of tyrosine-, tryptophan- and humic-like substances were identified in the tightly bound extracellular polymeric substances (TB-EPS). It was found that these fluorescence peaks could be quenched with Al(3+) at the dosage of 3.0 mg/L, which demonstrated that strong interactions took place between the EPS and Al(3+). The conditional stability constants for Al(3+) and EPS were determined by the Stern-Volmer equation. As to the binding mechanism, the -OH, N-H, C=O, C-N groups and the sulfur- and phosphorus-containing groups showed complexation action, although the groups in the LB-EPS and TB-EPS showed different behavior. The TB-EPS have stronger binding ability to Al(3+) than the LB-EPS, and TB-EPS play an important role in the interaction with Al(3+). PMID- 24218822 TI - Speciation of organic phosphorus in a sediment profile of Lake Taihu. II. Molecular species and their depth attenuation. AB - The understanding of organic phosphorus (P) dynamics in sediments requires information on their species at the molecular level, but such information in sediment profiles is scarce. A sediment profile was selected from a large eutrophic lake, Lake Taihu (China), and organic P species in the sediments were detected using solution phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) following extraction of the sediments with a mixture of 0.25 mol/L NaOH and 50 mmol/L EDTA (NaOH-EDTA) solution. The results showed that P in the NaOH EDTA extracts was mainly composed of orthophosphate, orthophosphate monoesters, phospholipids, DNA, and pyrophosphate. Concentrations of the major organic P compound groups and pyrophosphate showed a decreasing trend with the increase of depth. Their half-life times varied from 3 to 27 years, following the order of orthophosphate monoesters > phospholipids > or = DNA > pyrophosphate. Principal component analysis revealed that the detected organic P species had binding phases similar to those of humic acid-associated organic P (NaOH-NRP(HA)), a labile organic P pool that tends to transform to recalcitrant organic P pools as the early diagenetic processes proceed. This demonstrated that the depth attenuation of the organic P species could be partly attributed to their increasing immobilization by the sediment solids, while their degradation rates should be significantly lower than what were suggested in previous studies. PMID- 24218823 TI - Adsorption of heavy metal ions from aqueous solution by carboxylated cellulose nanocrystals. AB - A novel nanoadsorbent for the removal of heavy metal ions is reported. Cotton was first hydrolyzed to obtain cellulose nanocrystals (CNCs). CNCs were then chemically modified with succinic anhydride to obtain SCNCs. The sodic nanoadsorbent (NaSCNCs) was further prepared by treatment of SCNCs with saturated NaHCO3 aqueous solution. Batch experiments were carried out with SCNCs and NaSCNCs for the removal of Pb2+ and Cd2+. The effects of contact time, pH, initial adsorption concentration, coexisting ions and the regeneration performance were investigated. Kinetic studies showed that the adsorption equilibrium time of Pb2+ and Cd2+ was reached within 150 min on SCNCs and 5 min on NaSCNCs. The adsorption capacities of Pb2+ and Cd2+ on SCNCs and NaSCNCs increased with increasing pH. The adsorption isotherm was well fitted by the Langmuir model. The maximum adsorption capacities of SCNCs and NaSCNCs for Pb2+ and Cd2+ were 367.6 mg/g, 259.7 mg/g and 465.1 mg/g, 344.8 mg/g, respectively. SCNCs and NaSCNCs showed high selectivity and interference resistance from coexisting ions for the adsorption of Pb2+. NaSCNCs could be efficiently regenerated with a mild saturated NaCl solution with no loss of capacity after two recycles. The adsorption mechanisms of SCNCs and NaSCNCs were discussed. PMID- 24218824 TI - Synthesis of mesoporous Cu/Mg/Fe layered double hydroxide and its adsorption performance for arsenate in aqueous solutions. AB - The mesoporous Cu/Mg/Fe layered double hydroxide (Cu/Mg/Fe-LDH) with carbonate intercalation was synthesized and used for the removal of arsenate from aqueous solutions. The Cu/Mg/Fe-LDH was characterized by Fourier transform infrared spectrometry, X-ray diffraction crystallography, scanning electron microscopy, X ray photoelectron spectroscopy and Brunauer-Emmett-Teller. Effects of various physico-chemical parameters such as pH, adsorbent dosage, contact time and initial arsenate concentration on the adsorption of arsenate onto Cu/Mg/Fe-LDH were investigated. Results showed that it was efficient for the removal of arsenate, and the removal efficiency of arsenate increased with the increment of the adsorbent dosage, while the arsenate adsorption capacity decreased with increase of initial pH from 3 to 11. The adsorption isotherms can be well described by the Langmuir model with R2 > 0.99. Its adsorption kinetics followed the pseudo second-order kinetic model. Coexisting ions such as HPO4(2-), CO3(2-), SO4(2-) and NO3(-) could compete with arsenate for adsorption sites on the Cu/Mg/Fe-LDH. The adsorption of arsenate on the adsorbent can be mainly attributed to the ion exchange process. It was found that the synthesized Cu/Mg/Fe-LDH can reduce the arsenate concentration down to a final level of < 10 microg/L under the experimental conditions, and makes it a potential material for the decontamination of arsenate polluted water. PMID- 24218825 TI - Advanced regeneration and fixed-bed study of ammonium and potassium removal from anaerobic digested wastewater by natural zeolite. AB - Highly efficient regeneration of natural zeolite was developed in conjunction with the removal of high concentrations of ammonia and potassium from the reverse osmosis effluent of anaerobic-digested wastewater by fixed-bed ion exchange. The elution and uptake behavior of ammonium and potassium in the fixed bed were studied. Both batch desorption tests and on-column regeneration were conducted to develop an optimum regeneration condition compatible with the wastewater requirements. The effectiveness of ammonium elution increased with increasing alkaline concentration. The increase of salt dose significantly enhanced the ammonium maximum in the elution solution. Complete ammonium elution was achieved in 6 bed volumes (BV) when the alkaline and salt concentrations were respectively 0.1 mol/L and 18.6 g/L at a flow rate of 2.5-3.0 BV/hr. Due to the higher affinity of potassium with natural clinoptilolite, complete potassium elution was not achieved in all cases. PMID- 24218826 TI - Eutrophication development and its key regulating factors in a water-supply reservoir in North China. AB - Yanghe Reservoir is an important source of drinking water for Qinhuangdao City, North China; however, in recent decades this water source has been eutrophic with recurrent summer cyanobacterial blooms. The trophic grade of the system in summer was mesotrophic-eutrophic in 1990 and became hypertrophic in 2011. The nutrient availability is extremely high during the entire year, and the water temperature should be the primary driver of the summer blooms. In May-October of 2010 and 2011, abrupt variations were observed in the Secchi depth (SD) and chlorophyll a (Chl-a), and both the correlated analysis of Chl-a-SD and trophic status indices (TSI) deviation (TSI(Chl-a)-TSI(SD)) showed that algal cell density dominated light attenuation. During the algal bloom outbreak, the microcystin concentration was found to vary between 0.35-2.12 microg/L in 2010 and 0.11-1.86 microg/L in 2011. The maximum microcystin content was more than two times the safety limit required for drinking water. Inflow discharges were most concentrated in the summer, with periods of lower residence time and the largest water level fluctuation over the entire year. When a high availability of nutrients promoted a high Chl-a concentration in the whole system, it appeared that the instability caused by the decrease in residence time could not produce effective changes in the cyanobacterial abundance. The results indicated that nutrient enrichment in the aquatic systems of Yanghe Reservoir is the most serious problem and that the status would not been modified effectively by increasing hydrological fluctuations (e.g., decreasing the residence time). Therefore, decreasing the nutrient concentrations is the only route to improve the water quality of this reservoir. PMID- 24218827 TI - Laboratory-scale column study for remediation of TCE-contaminated aquifers using three-section controlled-release potassium permanganate barriers. AB - A laboratory-scale study with a sand column was designed to simulate trichloroethylene (TCE) pollution in the aquifer environment with three-section controlled-release potassium permanganate (CRP) barriers. The main objective of this study was to evaluate the feasibility of CRP barriers in remediation of TCE in aquifers in a long-term and controlled manner. CRP particles with a 1:3 molar ratio of KMnO4 to stearic acid showed the best controlled-release properties in pure water, and the theoretical release time was 138.5 days. The results of TCE removal in the test column indicated that complete removal efficiency of TCE in a sand column by three-section CRP barriers could be reached within 15 days. The molar ratio of KMnO4 to TCE in the three-section CRP barriers was 16:1, which was much lower than 82:1 as required when KMnO4 solution is used directly to achieve complete destruction of TCE. This result revealed that the efficiency of CRP for remediation of TCE was highly improved after encapsulation. PMID- 24218828 TI - Influence of chironomid larvae on oxygen and nitrogen fluxes across the sediment water interface (Lake Taihu, China). AB - The microscale distribution of oxygen, the nitrogen flux and the denitrification rates in sediment inhabited by chironomid larvae (Tanypus chinensis) were measured in eutrophic Lake Taihu, China. The presence of the chironomids in the sediment increased the oxygen diffusional flux from 10.4 +/- 1.4 to 12.7 +/- 2.5 mmol O2/(m2 x day). The burrows of the larvae represented "hot spots" and strongly influenced the nitrogen cycles and diagenetic activity in the sediment. The results indicate that the bioturbation effects of Tanypus chinensis chironomid larvae increased the capacity of the sediment as a sink for nitrate and a source for ammonium. Nitrate influx and ammonium outflux were increased 8.8 and 1.7 times, respectively. Under bioturbation, the amount of nitrate consumed was greater than the amount of ammonium released. The total denitrification rate was also enhanced from 0.76 +/- 0.34 to 5.50 +/- 1.30 mmol N/(m2 x day). The net effect was that the bioturbated sediments acted as a net sink for inorganic nitrogen under direct and indirect bioturbation effects compared to the control. PMID- 24218829 TI - Comparison of different phosphate species adsorption by ferric and alum water treatment residuals. AB - As safe byproducts of drinking water treatment processes, ferric and alum water treatment residuals (FARs) have the potential to be new phosphate (P) immobilization materials. In this study, batch experiments were conducted to investigate and compare the adsorption characteristics of three P species by FARs. The results showed that the kinetic processes of different P species' adsorption by FARs could be described by a pseudo second-order model. The ranking list of the initial adsorption rates with respect to different phosphates was pyrophosphate, phytate, orthophosphate, hexametaphosphate and glycerophosphate. Of the six models considered, the two-site Langmuir model most effectively described the adsorption characteristics of the various P species. Upon fitting the results, the maximum adsorption capacities were determined to be 40.24 mg/g for phytate, 18.04 mg/g for pyrophosphate, 17.14 mg/g for orthophosphate, 15.86 mg/g for hexametaphosphate and 10.81 mg/g for glycerophosphate. In addition, the adsorption processes of the different P species were spontaneous endothermic processes and were favored at lower pH values. The pH dependency was found to be especially true for orthophosphate, where the adsorption capacity decreased by 1.22 mg/g with an increase in pH from 5 to 9. Fractionation of the adsorbed P species from the FARs demonstrated that Al-P and Fe-P were the dominating forms, constituting approximately 80%-90% of the total P fractions, which indicated that the adsorbed P species had a low leaching risk and could stably exist in the FARs. Therefore, the FARs could be effective in controlling pollution in water caused by different P species. PMID- 24218830 TI - Removal efficiency of fluoride by novel Mg-Cr-Cl layered double hydroxide by batch process from water. AB - The fluoride ion removal from aqueous solution using synthesized Mg-Cr-Cl layered double hydroxide has been reported. Mg-Cr-Cl was characterized by X-ray powder diffraction, Fourier-transform infrared, thermo-gravimetric analysis, differential thermal analysis, and scanning electron microscope. Adsorption experiments were carried out in batch mode as a function of adsorption dosages, contact time, pH, and initial fluoride concentration to get optimum adsorption capacity. The adsorption kinetic study showed that the adsorption process followed first order kinetics. The fluoride removal was 88.5% and 77.4% at pH 7 with an adsorbent dose of 0.6 g/100 mL solution and initial fluoride concentration of 10 mg/L and 100 mg/L, respectively. The equilibrium was established at 40 min. Adsorption experiment data were fitted well with Langmuir isotherm with R2 = 0.9924. Thermodynamic constants were also measured and concluded that the adsorption process was spontaneous and endothermic in nature. The removal percentage decreased slowly with increasing pH. This process is suitable for industrial effluents. The regeneration of the material is not possible. PMID- 24218831 TI - Determining reference conditions for TN, TP, SD and Chl-a in eastern plain ecoregion lakes, China. AB - Establishing the nutrient reference condition (baseline environmental condition) of lakes in an ecoregion is a critical consideration in the development of scientifically defensible aquatic nutrient criteria. Three methods were applied to determine reference conditions in the Eastern plain ecoregion lakes with respect to total phosphorus (TP), total nitrogen (TN), planktonic chlorophyll a (Chl-a) and Secchi depth (SD). The reference condition value for the lakes in the Eastern plain ecoregion by the trisection method is TP of 0.029 mg/L, TN of 0.67 mg/L, Chl-a of 3.92 mg/m3, SD of 0.85 m, and the reference condition range by the lake population distribution approach is TP of 0.014-0.043 mg/L, TN of 0.360 0.785 mg/L, Chl-a of 1.78-4.73 mg/m3, SD of 0.68-1.21 m. Additionally, empirical models were developed for estimating the reference Chl-a concentration and SD successfully for lakes in the Eastern plain ecoregion. Overall, the data suggest that multiple methods can be used to determine reference conditions and that in Eastern plain ecoregion lakes the reference condition corresponds to a mesotrophic status. PMID- 24218832 TI - Nitrate in shallow groundwater in typical agricultural and forest ecosystems in China, 2004-2010. AB - The nitrate-nitrogen (NO3(-)-N) concentrations from shallow groundwater wells situated in 29 of the Chinese Ecosystem Research Network field stations, representing typical agro- and forest ecosystems, were assessed using monitoring data collected between 2004 and 2010. Results from this assessment permit a national scale assessment of nitrate concentrations in shallow groundwater, and allow linkages between nitrate concentrations in groundwater and broad land use categories to be made. Results indicated that most of the NO3(-)-N concentrations in groundwater from the agro- and forest ecosystems were below the Class 3 drinking water standard stated in the Chinese National Standard: Quality Standard for Ground Water (< or = 20 mg/L). Over the study period, the average NO3(-)-N concentrations were significantly higher in agro-ecosystems (4.1 +/- 0.33 mg/L) than in forest ecosystems (0.5 +/- 0.04 mg/L). NO3(-)-N concentrations were relatively higher (> 10 mg N /L) in 10 of the 43 wells sampled in the agricultural ecosystems. These elevated concentrations occurred mainly in the Ansai, Yucheng, Linze, Fukang, Akesu, and Cele field sites, which were located in arid and semi-arid areas where irrigation rates are high. We suggest that improvements in N fertilizer application and irrigation management practices in the arid and semi-arid agricultural ecosystems of China are the key to managing groundwater nitrate concentrations. PMID- 24218833 TI - Influential factors of formation kinetics of flocs produced by water treatment coagulants. AB - The growth rate and size of floc formation is of great importance in water treatment especially in coagulation process. The floc formation kinetics and the coagulation efficiency of synthetic water were investigated by using an on-line continuous optical photometric dispersion analyze and the analysis of water quality. Experimental conditions such as alum dosage, pH value for coagulation, stirring intensity and initial turbidity were extensively examined. The photometric dispersion analyze results showed that coagulation of kaolin suspensions with two coagulants (alum and polyaluminium chloride) could be taken as a two-phase process: slow and rapid growth periods. Operating conditions with higher coagulant doses, appropriate pH and average shear rate might be particularly advantageous. The rate of overall floc growth was mainly determined by a combination of hydraulic and water quality conditions such as pH and turbidity. The measurement of zeta potential indicates that polyaluminium chloride exhibited higher charge-neutralizing ability than alum and achieved lower turbidities than alum for equivalent Al dosages. Under the same operating conditions, the alum showed a higher grow rate, but with smaller floc size. PMID- 24218834 TI - Characterization and performance of Pt/SBA-15 for low-temperature SCR of NO by C3H6. AB - Pt supported on mesoporous silica SBA-15 was investigated as a catalyst for low temperature selective catalytic reduction (SCR) of NO by C3H6 in the presence of excess oxygen. The prepared catalysts were characterized by means of XRD, BET surface area, TEM, NO-TPD, NO/C3H6-TPO, NH3-TPD, XPS and 27Al MAS NMR. The effects of Pt loading amount, O2/C3H6 concentration, and incorporation of Al into SBA-15 have been studied. It was found that the removal efficiency increased significantly after Pt loading, but an optimal loading amount was observed. In particular, under an atmosphere of 150 ppm NO, 150 ppm C3H6, and 18 vol.% O2, 0.5% Pt/SBA-15 showed remarkably high catalytic performance giving 80.1% NOx reduction and 87.04% C3H6 conversion simultaneously at 140 degrees C. The enhanced SCR activity of Pt/SBA-15 is associated with its outstanding oxidation activities of NO to NO2 and C3H6 to CO2 in low temperature range. The research results also suggested that higher concentration of O2 and higher concentration of C3H6 favored NO removal. The incorporation of Al into SBA-15 improved catalytic performance, which could be ascribed to the enhancement of catalyst surface acidity caused by tetrahedrally coordinated AlO4. Moreover, the catalysts could be easily reused and possessed good stability. PMID- 24218835 TI - Photo-catalytic decolourisation of toxic dye with N-doped titania: a case study with Acid Blue 25. AB - Dyes are one of the hazardous water pollutants. Toxic Acid Blue 25, an anthraquinonic dye, has been decolourised by photo-catalysing it with nitrogen doped titania in aqueous medium. The photo catalyst was prepared from 15% TiCl3 and 25% aqueous NH3 solution as precursor. XRD and TEM revealed the formation of well crystalline anatase phase having particle size in the nano-range. BET surface area of the sample was higher than that of pure anatase TiO2. DRS showed higher absorption of radiation in visible range compared to pure anatase TiO2. XPS revealed the presence of nitrogen in N-Ti-O environment. The experimental parameters, namely, photocatalyst dose, initial dye concentration as well as solution pH influence the decolourisation process. At pH 3.0, the N-TiO2 could decolourise almost 100% Acid Blue 25 within one hour. The influence of N-TiO2 dose, initial concentration of Acid Blue 25 and solution pH on adsorption desorption equilibrium is also studied. The adsorption process follows Lagergren first order kinetics while the modified Langmuir-Hinselwood model is suitably fitted for photocatalytic decolourisation of Acid Blue 25. PMID- 24218836 TI - Pb(II) removal from water using Fe-coated bamboo charcoal with the assistance of microwaves. AB - Bamboo charcoal (BC) was used as starting material to prepare iron-modified bamboo charcoal (Fe-MBC) by its impregnation in FeCl3 and HNO3 solutions simultaneously, followed by microwave heating. The material can be used as an adsorbent for Pb(II) contaminants removal in water. The composites were prepared with Fe molar concentration of 0.5, 1.0 and 2.0 mol/L and characterized by means of N2 adsorption-desorption isotherms, X-ray diffraction spectroscopy (XRD), scanning electron microscopy coupled with energy dispersive X-ray spectrometry (SEM-EDS), Fourier transform infrared (FT-IR) and point of zero charge (pH(pzc)) measurements. Nitrogen adsorption analyses showed that the BET specific surface area and total pore volume increased with iron impregnation. The adsorbent with Fe molar concentration of 2 mol/L (2Fe-MBC) exhibited the highest surface area and produced the best pore structure. The Pb(II) adsorption process of 2Fe-MBC and BC were evaluated in batch experiments and 2Fe-MBC showed an excellent adsorption capability for removal Pb(II). The adsorption of Pb(II) strongly depended on solution pH, with maximum values at pH 5.0. The ionic strength had a significant effect on the adsorption at pH < 6.0. The adsorption isotherms followed the Langmuir isotherm model well, and the maximum adsorption capacity for Pb(II) was 200.38 mg/g for 2Fe-MBC. The adsorption processes were well fitted by a pseudo second-order kinetic model. Thermodynamic parameters showed that the adsorption of Pb(II) onto Fe-MBC was feasible, spontaneous, and exothermic under the studied conditions, and the ion exchange mechanism played an significant role. These results have important implications for the design of low-cost and effective adsorbents in the removal of Pb(II) from wastewater. PMID- 24218837 TI - Application potential of carbon nanotubes in water treatment: A review. AB - Water treatment is the key to coping with the conflict between people's increasing demand for water and the world-wide water shortage. Owing to their unique and tunable structural, physical, and chemical properties, carbon nanotubes (CNTs) have exhibited great potentials in water treatment. This review makes an attempt to provide an overview of potential solutions to various environmental challenges by using CNTs as adsorbents, catalysts or catalyst support, membranes, and electrodes. The merits of incorporating CNT to conventional water-treatment material are emphasized, and the remaining challenges are discussed. PMID- 24218838 TI - Characterization, treatment and releases of PBDEs and PAHs in a typical municipal sewage treatment plant situated beside an urban river, East China. AB - Characterization, treatment and releases of eight polybrominated diphenyl ethers (PBDEs) congeners and sixteen polycyclic aromatic hydrocarbons (PAHs) in wastewater were evaluated along the treatment processes of a typical secondary treatment municipal sewage treatment plant (STP) (in Hefei City) situated the beside Nanfei River, East China. The findings showed that the average concentrations of the total PBDEs in raw wastewater and treated effluent were 188.578 and 36.884 ng/L respectively. Brominated diphenyl ether (BDE) 209 congener, the predominant PBDE in the STP and Nanfei River, could be related to the discharge of car-industry-derived wastes. For PAHs, the average concentrations in raw wastewater and treated effluent were 5758.8 and 2240.4 ng/L respectively, with naphthalene, benzo[a]pyrene and indeno[1,2,3-c,d]pyrene being detected at the highest concentrations. PAHs mainly originate from the combustion of biomass/coal and petroleum. The STP reduced about 80% of the PBDEs and 61% of the PAHs, which were eliminated mainly by sedimentation processes. The removal rates of PBDEs/PAHs increased with the increase of their solid-water partitioning coefficients. Accordingly, the STP's effluent, containing some PBDE congeners (e.g., BDE 47, 99 and 209, etc.) and low-molecular-weight PAHs, could be an important contributor of these contaminants' input to Nanfei River. It resulted in a significant increase of PBDE/PAH concentrations and PAH toxicological risk in the river water downstream. About 4.040 kg/yr of PBDEs and 245.324 kg/yr of PAHs could be released into the Nanfei River. The current conventional wastewater treatment processes should be improved to remove the relatively low-molecular weight PBDEs/PAHs more effectively. PMID- 24218840 TI - Assessment of heavy metal enrichment and its human impact in lacustrine sediments from four lakes in the mid-low reaches of the Yangtze River, China. AB - Sediments from four lakes in the mid-low reaches of the Yangtze River, Taibai Lake, Longgan Lake, Chaohu Lake and Xijiu Lake, were chosen to evaluate their enrichment state and history. The state of heavy metal enrichment was at a low level in the sediment of Taibai Lake and Longgan Lake. The enrichment state of Co, Cr and Ni was also low in the sediment of Chaohu Lake and Xijiu Lake, while Cu, Pb and Zn enrichment reached a higher level. Mass accumulation fluxes were calculated to quantitatively evaluate the anthropogenic contribution to heavy metals in the sediment. The anthropogenic accumulation fluxes were lower in the sediment of Taibai Lake and Longgan Lake compared with the other two lakes, where heavy metals, especially Cu, Pb and Zn, were mainly from anthropogenic sources. Heavy metal accumulation did not vary greatly in the sediment of Taibai Lake and Longgan Lake, while that in Chaohu Lake and Xijiu Lake increased since the 1950s and substantially increased since the 1980s, although a decrease occurred since 2000 AD in Xijiu Lake. Heavy metal enrichment was strongly related to human activities in the catchment. The development of urbanization and industrialization was much more rapid in the catchments of Chaohu Lake and Xijiu Lake than of the other two lakes, and thus large amounts of anthropogenically sourced heavy metals were discharged into the lakes, which resulted in a higher contamination risk. However, human activities in the Longgan Lake and Taibai Lake catchments mainly involved agriculture, which contributed a relatively small portion of heavy metals to the lakes. PMID- 24218839 TI - Factors influencing antibiotics adsorption onto engineered adsorbents. AB - The study evaluated the adsorption of two antibiotics by four engineered adsorbents (hypercrosslinked resin MN-202, macroporous resin XAD-4, activated carbon F-400, and multi-walled carbon nanotubes (MWCNT)) from aqueous solutions. The dynamic results demonstrated the dominant influence of pore size in adsorption. The adsorption amounts of antibiotics on XAD-4 were attributed to the hydrophobic effect, whereas steric hindrance or micropore-filling played a main role in the adsorption of antibiotics by F-400 because of its high microporosity. Aside from F-400, similar patterns of pH-dependent adsorption were observed, implying the importance of antibiotic molecular forms to the adsorption process for adsorbents. Increasing the ionic concentration with CaC12 produced particular adsorption characteristics on MWCNT at pH 2.0 and F-400 at pH 8.0, which were attributed to the highly available contact surfaces and molecular sieving, respectively. Its hybrid characteristics incorporating a considerable portion of mesopores and micropores made hypercross linked MN-202 a superior antibiotic adsorbent with high adsorption capacity. Furthermore, the adsorption capacity of MWCNT on the basis of surface area was more advantageous than that of the other adsorbents because MWCNT has a much more compact molecular arrangement. PMID- 24218841 TI - Biodegradation of 2-methylquinoline by Enterobacter aerogenes TJ-D isolated from activated sludge. AB - Bacterial strain Enterobacter aerogenes TJ-D capable of utilizing 2 methylquinoline as the sole carbon and energy source was isolated from acclimated activated sludge under denitrifying conditions. The ability to degrade 2 methylquinoline by E. aerogenes TJ-D was investigated under denitrifying conditions. Under optimal conditions of temperature (35 degrees C) and initial pH 7, 2-methylquinoline of 100 mg/L was degraded within 176 hr. The degradation of 2 methylquinoline by E. aerogenes TJ-D could be well described by the Haldane model (R2 > 0.91). During the degradation period of 2-methylquinoline (initial concentration 100 mg/L), nitrate was almost completely consumed (the removal efficiency was 98.5%), while nitrite remained at low concentration (< 0.62 mg/L) during the whole denitrification period. 1,2,3,4-Tetrahydro-2-methylquinoline, 4 ethyl-benzenamine, N-butyl-benzenamine, N-ethyl-benzenamine and 2,6-diethyl benzenamine were metabolites produced during the degradation. The degradation pathway of 2-methylquinoline by E. aerogenes TJ-D was proposed. 2-Methylquinoline is initially hydroxylated at C-4 to form 2-methyl-4-hydroxy-quinoline, and then forms 2-methyl-4-quinolinol as a result of tautomerism. Hydrogenation of the heterocyclic ring at positions 2 and 3 produces 2,3-dihydro-2-methyl-4 quinolinol. The carbon-carbon bond at position 2 and 3 in the heterocyclic ring may cleave and form 2-ethyl-N-ethyl-benzenamine. Tautomerism may result in the formation of 2,6-diethyl-benzenamine and N-butyl-benzenamine. 4-Ethyl-benzenamine and N-ethyl-benzenamine were produced as a result of losing one ethyl group from the above molecules. PMID- 24218842 TI - Inactivation, reactivation and regrowth of indigenous bacteria in reclaimed water after chlorine disinfection of a municipal wastewater treatment plant. AB - Disinfection of reclaimed water prior to reuse is important to prevent the transmission of pathogens. Chlorine is a widely utilized disinfectant and as such is a leading contender for disinfection of reclaimed water. To understand the risks of chlorination resulting from the potential selection of pathogenic bacteria, the inactivation, reactivation and regrowth rates of indigenous bacteria were investigated in reclaimed water after chlorine disinfection. Inactivation of total coliforms, Enterococcus and Salmonella showed linear correlations, with constants of 0.1384, 0.1624 and 0.057 L/(mg.min) and R2 of 0.7617, 0.8316 and 0.845, respectively. However, inactivation of total viable cells by measurement of metabolic activity typically showed a linear correlation at lower chlorine dose (0-22 (mg-min)/L), and a trailing region with chlorine dose increasing from 22 to 69 (mg.min)/L. Reactivation and regrowth of bacteria were most likely to occur after exposure to lower chlorine doses, and extents of reactivation decreased gradually with increasing chlorine dose. In contrast to total coliforms and Enterococcus, Salmonella had a high level of regrowth and reactivation, and still had 2% regrowth even after chlorination of 69 (mg.min)/L and 24 hr storage. The bacterial compositions were also significantly altered by chlorination and storage of reclaimed water, and the ratio of Salmonella was significantly increased from 0.001% to 0.045% after chlorination of 69 (mg.min)/L and 24 hr storage. These trends indicated that chlorination contributes to the selection of chlorine-resistant pathogenic bacteria, and regrowth of pathogenic bacteria after chlorination in reclaimed water with a long retention time could threaten public health security during wastewater reuse. PMID- 24218843 TI - Photochemical degradation of nonylphenol in aqueous solution: the impact of pH and hydroxyl radical promoters. AB - The degradation of nonylphenol (NP) in aqueous solution with UV, H2O2/UV, and Fenton/photo-Fenton processes was studied. The efficacy of direct and hydrogen peroxide photolysis proved to be dependent on the pH value. The addition of H2O2 to UV treatment improved NP degradation. The application of UV photolysis and the H2O2/UV system at pH 7 resulted in low pseudo first-order rate constants at 10-4 sec-1. In the experiments at elevated pH values the pseudo-first order rate constants increased to 10-3 sec-1. The efficacy of the Fenton process was lower in comparison with UV and hydrogen peroxide photolysis. The addition of UV irradiation to the H2O2/Fe2+ system substantially improved NP degradation efficacy. In terms of performance, the photo-Fenton process was similar to the H2O2/UV process. The most favourable process for complete nonylphenol degradation considering both operational cost and treatment efficacy was H202/UV at pH 11 and 250 micromol/L H2O2. PMID- 24218844 TI - A pilot-scale study of cryolite precipitation from high fluoride-containing wastewater in a reaction-separation integrated reactor. AB - Fluoride removal by traditional precipitation generates huge amounts of a water rich sludge with low quality, which has no commercial or industrial value. The present study evaluated the feasibility of recovering fluoride as low water content cryolite from industrial fluoride-containing wastewater. A novel pilot scale reaction-separation integrated reactor was designed. The results showed that the seed retention time in the reactor was prolonged to strengthen the induced crystallization process. The particle size of cryolite increased with increasing seed retention time, which decreased the water content. The recovery rate of cryolite was above 75% under an influent fluoride concentration of 3500 mg/L, a reaction temperature of 500C, and an influent flow of 40 L/hr. The cryolite products that precipitated from the reactor were small in volume, large in particle size, low in water content, high in crystal purity, and recyclable. PMID- 24218845 TI - Effect of phosphogypsum and dicyandiamide as additives on NH3, N20 and CH4 emissions during composting. AB - A laboratory scale experiment of composting in a forced aeration system using pig manure with cornstalks was carried out to investigate the effects of both phosphogypsum and dicyandiamide (DCD, C2H4N4) as additives on gaseous emissions and compost quality. Besides a control, there were three amended treatments with different amounts of additives. The results indicated that the phosphogypsum addition at the rate of 10% of mixture dry weight decreased NH3 and CH4 emissions significantly during composting. The addition of DCD at the rate of 0.2% of mixture dry weight together with 10% of phosphogypsum further reduced the N2O emission by affecting the nitrification process. Reducing the phosphogypsum addition to 5% in the presence of 0.2% DCD moderately increased the NH3 emissions but not N2O emission. The additives increased the ammonium content and electrical conductivity significantly in the final compost. No adverse effect on organic matter degradation or the germination index of the compost was found in the amended treatments. It was recommended that phosphogypsum and DCD could be used in composting for the purpose of reducing NH3, CH4 and N2O emissions. Optimal conditions and dose of DCD additive during composting should be determined with different materials and composting systems in further study. PMID- 24218846 TI - Evaluation of heavy metal contamination hazards in nuisance dust particles, in Kurdistan Province, western Iran. AB - The effects of natural and geochemical factors depending on heavy metal contamination in nuisance dust particles were evaluated. The nuisance dust particles were sampled using passive deposit gauge method for one year from April 2010 to March 2011 and the obtained samples were measured for the total contents and the contamination levels of Fe, Mn, Cu and As using geo-accumulation index (l(geo)), enrichment factor (EF) and the integrated pollution index (IPI). The results showed that, the contamination levels of Fe and Mn based on I(geo) values, were uncontaminated (I(geo) < 0) (variations of the I(geo) index was from -3.11 to -1.751 for Fe, from -0.630 to -1.925 for Mn), while the values of Cu and As were demonstrated to have moderate contamination based on l(geo) values (variations of I(geo) index was from -1.125 to 0.848 for Cu, and from -2.002 to 1.249 for As). The analysis of EF also revealed minor to moderate enrichment for Mn (1.215-4.214), minor to moderately severe enrichment for Cu (2.791-6.484), and As (1.370-8.462), respectively. The variation of the IPI index also showed low to moderate level of heavy metal pollution in nuisance dust particulates (0.511 1.829). The analysis of the results also approved that the natural processes and geochemical variables (the changing meteorological parameters) can significantly affect the availability of heavy metals in nuisance dust particles in Western Iran. PMID- 24218847 TI - Utilizing surfactants to control the sorption, desorption, and biodegradation of phenanthrene in soil-water system. AB - An integrative technology including the surfactant enhanced sorption and subsequent desorption and biodegradation of phenanthrene in the soil-water system was introduced and tested. For slightly contaminated agricultural soils, cationic nonionic mixed surfactant-enhanced sorption of organic contaminants onto soils could reduce their transfer to plants, therefore safe-guarding agricultural production. After planting, residual surfactants combined with added nonionic surfactant could also promote the desorption and biodegradation of residual phenanthrene, thus providing a cost-effective pollution remediation technology. Our results showed that the cationic-nonionic mixed surfactants dodecylpyridinium bromide (DDPB) and Triton X-100 (TX100) significantly enhanced soil retention of phenanthrene. The maximum sorption coefficient Kd of phenanthrene for contaminated soils treated by mixed surfactants was about 24.5 times that of soils without surfactant (Kd) and higher than the combined effects of DDPB and TX100 individually, which was about 16.7 and 1.5 times Kd, respectively. On the other hand, TX100 could effectively remove phenanthrene from contaminated soils treated by mixed surfactants, improving the bioavailability of organic pollutants. The desorption rates of phenanthrene from these treated soils were greater than 85% with TX100 concentration above 2000 mg/L and approached 100% with increasing TX100 concentration. The biodegradation rates of phenanthrene in the presence of surfactants reached over 95% in 30 days. The mixed surfactants promoted the biodegradation of phenanthrene to some extent in 10-22 days, and had no obvious impact on phenanthrene biodegradation at the end of the experiment. Results obtained from this study provide some insight for the production of safe agricultural products and a remediation scheme for soils slightly contaminated with organic pollutants. PMID- 24218848 TI - Detoxifying PCDD/Fs and heavy metals in fly ash from medical waste incinerators with a DC double are plasma torch. AB - Medical waste incinerator (MWI) fly ash is regarded as a highly toxic waste because it contains high concentrations of heavy metals and dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Therefore fly ash from MWI must be appropriately treated before being discharged into the environment. A melting process based on a direct current thermal plasma torch has been developed to convert MWI fly ash into harmless slag. The leaching characteristics of heavy metals in fly ash and vitrified slag were investigated using the toxicity characteristic leaching procedure, while the content of PCDD/Fs in the fly ashes and slags was measured using method 1613 of the US EPA. The experimental results show that the decomposition rate of PCDD/Fs is over 99% in toxic equivalent quantity value and the leaching of heavy metals in the slag significantly decreases after the plasma melting process. The produced slag has a compact and homogeneous microstructure with density of up to 2.8 g/cm3. PMID- 24218849 TI - Role of sorbent surface functionalities and microporosity in 2,2',4,4' tetrabromodiphenyl ether sorption onto biochars. AB - The study provides insight into the combined effect of sorbent surface functionalities and microporosity on 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) sorption onto biochars. A series of biochars prepared under different conditions were used to test their sorption behaviors with BDE-47. The extents of sorption behaviors were parameterized in terms of the single-point adsorption equilibrium constant (Koc) at three equilibrium concentration (Ce) levels (0.001Sw (solubility), 0.005Sw, and 0.05Sw) which was determined using the Freundlich model. To elucidate the concentration-dependent dominant mechanisms for BDE-47 sorption onto biochars, Ko was correlated with four major parameters using multiple parameter linear analysis accompanied with significance testing. The results indicated that at low concentration (Ce = 0.001Sw), the surface microporosity term, which represented a pore-filling mechanism, contributed significantly to this relationship, while as concentration was increased to higher levels, surface functionality related to surface adsorption began to take the dominant role, which was further confirmed by the results of Polanyi-based modeling. Given the above results, a dual mode model based on Dubinin Radushkevich and de Boer-Zwikker equations was adopted to quantitatively assess the changes of significance of surface adsorption as well as that of pore filling with sorption process development. In addition, UV spectra of four typical aromatic compounds which represented the key structural fragments of biochars before and after interactions with BDE-47 were analyzed to determine the active functional groups and supply complementary evidence for the dominant interaction force for surface adsorption, based on which eta-eta electron-donor-acceptor interaction was proposed to contribute greatly to surface adsorption. PMID- 24218850 TI - Systematic analysis of microfauna indicator values for treatment performance in a full-scale municipal wastewater treatment plant. AB - The indicator values of microfauna functional groups and species for treatment performance were systematically evaluated based on the continuous monitoring of the entire microfauna communities including both protozoa and metazoa over a period of 14 months, in two parallel full-scale municipal wastewater treatment systems in a plant in Beijing, China. A total of 57 species of ciliates, 14 species (units) of amoebae, 14 species (units) of flagellates and 4 classes of small metazoa were identified, with Arcella hemisphaerica, Vorticella striata, Vorticella convallaria, Epistylis plicatilis and small flagellates (e.g. Bodo spp.) as the dominant protozoa, and rotifers as the dominant metazoa. The abundance of the sessile ciliates was correlated with the removals of BOD5 (Pearson's r = 0.410, p < 0.05) and CODcr (r = 0.397, p < 0.05) while the testate amoebae was significantly positively related to nitrification (r = 0.523, p < 0.01). At the same time, some other associations were also identified: the abundances of the large flagellates (r = 0.447, p < 0.01), the metazoa (r = 0.718, p < 0.01) and species Aspidisca sulcata (r = 0.337, p < 0.05) were positively related to nitrification; the abundance of Aspidisca costata was correlated to the TN (total nitrogen) removal (r = -0.374, p < 0.05 ); the abundances of the sessile species Carchesium polypinum (r = 0.458, p < 0.01) and E. plicatilis (r = 0.377, p < 0.05) were correlated with the removal of suspended solids. PMID- 24218851 TI - Function of arsATorf7orf8 of Bacillus sp. CDB3 in arsenic resistance. AB - Bacillus sp. CDB3 isolated from an arsenic contaminated cattle dip site possesses an uncommon arsenic resistance (ars) operon bearing eight genes in the order of arsRYCDATorf7orf8. We investigated the functions of arsA, arsT, orf7 and orf8 in arsenic resistance using a plasmid-based gene knockout approach in the ars gene deficient Escherichia coli strain AW3110. The CDB3 arsA gene was shown to play a significant role in resistance, suggesting that the encoded ArsA may couple with the arsenite transporter, forming an ArsAY complex that can enhance arsenite extrusion efficiency. The disruption of either arsTor orf7 was not observed to affect arsenic resistance in the heterologous E. coli host, but their involvement in arsenic resistance can not be excluded. The orf8 gene is predicted to encode a putative dual-specificity protein phosphatase which also shares certain homology to arsenate reductases. The function loss of orf8 resulted in a remarkable decrease in resistance to arsenate, though not arsenite. To examine if this effect was due to the reduction of arsenate by orf8, the arsC gene within the 8 gene operon was disrupted. The resulting abolishment of arsenate resistance suggests that the involvement of orf8 in arsenic resistance is not via reductase activity. PMID- 24218852 TI - Enrichment, isolation and identification of sulfur-oxidizing bacteria from sulfide removing bioreactor. AB - Sulfur-oxidizing bacteria (SOB) are the main microorganisms that participate in the natural sulfur cycle. To obtain SOB with high sulfur-oxidizing ability under aerobic or anaerobic conditions, aerobic and anaerobic enrichments were carried out. Denaturing gradient gel electrophoresis (DGGE) profiles showed that the microbial community changed according to the thiosulfate utilization during enrichments, and Rhodopseudomonas and Halothiobacillus were the predominant bacteria in anaerobic enrichment and aerobic enrichment, respectively, which mainly contributed to the thiosulfate oxidization in the enrichments. Based on the enriched cultures, six isolates were isolated from the aerobic enrichment and four isolates were obtained from the anaerobic enrichment. Phylogenetic analysis suggested the 16S rRNA gene of isolates belonged to the genus Acinetobacter, Rhodopseudomonas, Pseudomonas, Halothiobacillus, Ochrobactrum, Paracoccus, Thiobacillus, and Alcaligenes, respectively. The tests suggested isolates related to Halothiobacillus and Rhodopseudomonas had the highest thiosulfate oxidizing ability under aerobic or anaerobic conditions, respectively; Paracoccus and Alcaligenes could aerobically and anaerobically oxidize thiosulfate. Based on the DGGE and thiosulfate oxidizing ability analysis, Rhodopseudomonas and Halothiobacillus were found to be the main SOB in the sulfide-removing reactor, and were responsible for the sulfur-oxidizing in the treatment system. PMID- 24218853 TI - In vitro immunotoxicity of untreated and treated urban wastewaters using various treatment processes to rainbow trout leucocytes. AB - Municipal effluents are known to impede the immune system of aquatic organisms. The purpose of this study was to examine the immunotoxicity of urban wastewaters before and after 6 treatment processes from 12 cities toward trout leucocytes. Freshly prepared trout leucocytes were exposed to increasing concentrations of solid phase (C18) extracts of wastewaters for 24 hr at 150C. Immunocompetence was determined by following changes in leucocyte viability and the proportion of cells able to ingest at least one (immunoactivity) and at least three (immunoefficiency) fluorescent beads. The influents were treated by six different treatment strategies consisting of facultative aerated lagoons, activated sludge, biological aerated filter, biological nutrient removal, chemically-assisted physical treatment and trickling filter/solid contact. Water quality parameters of the wastewaters revealed that the plants effectively removed total suspended solids and reduced the chemical oxygen demand. The results revealed that the effluents' immunotoxic properties were generally more influenced by the properties of the untreated wastewaters than by the treatment processes. About half of the incoming influents decreased leucocyte viability while 4 treatment plants were able to reduce toxicity. The influents readily increased phagocytosis activity for 8/12 influents while it was decreased in 4/12 influents. This increase was abolished for 4/12 of the effluents using treatments involving biological and oxidative processes. In conclusion, municipal effluents have the potential to alter the immune system in fish and more research will be needed to improve the treatments of wastewaters to better protect the quality of the aquatic environment. PMID- 24218854 TI - Using lysosomal membrane stability of haemocytes in Ruditapes philippinarum as a biomarker of cellular stress to assess contamination by caffeine, ibuprofen, carbamazepine and novobiocin. AB - Although pharmaceuticals have been detected in the environment only in the range from ng/L to microg/L, it has been demonstrated that they can adversely affect the health status of aquatic organisms. Lysosomal membrane stability (LMS) has previously been applied as an indicator of cellular well-being to determine health status in bivalve mussels. The objective of this study is to evaluate LMS in Ruditapes philippinarum haemolymph using the neutral red retention assay (NRRA). Clams were exposed in laboratory conditions to caffeine (0.1, 5, 15, 50 microg/L), ibuprofen (0.1, 5, 10, 50 microg/L), carbamazepine and novobiocin (both at 0.1, 1, 10, 50 microg/L) for 35 days. Results show a dose-dependent effect of the pharmaceuticals. The neutral red retention time measured at the end of the bioassay was significantly reduced by 50% after exposure to environmental concentrations (p < 0.05) (caffeine = 15 microg/L; ibuprofen = 10 microg/L; carbamazepine = 1 microg/L and novobiocin = 1 microg/L), compared to controls. Clams exposed to these pharmaceuticals were considered to present a diminished health status (retention time < 45 min), significantly worse than controls (96 min) (p < 0.05). The predicted no environmental effect concentration (PNEC) results showed that these pharmaceuticals are very toxic at the environmental concentrations tested. Measurement of the alteration of LMS has been found to be a sensitive technique that enables evaluation of the health status of clams after exposure to pharmaceuticals under laboratory conditions, thus representing a robust Tier-1 screening biomarker. PMID- 24218855 TI - Effect of transition metal doping under reducing calcination atmosphere on photocatalytic property of TiO2 immobilized on SiO2 beads. AB - TiO2 immobilized on SiO2 (TiO2/SiO2) have been prepared by sol-gel method and various ions of transition metals (Cr3+, Co2+ Ni2+, CU2+, and Zn2+) were doped on the photocatalyst using wet impregnation method under reducing calcination atmosphere. The photocatalytic activity of metal doped TiO2/SiO2 towards phenol degradation under black light irradiation were investigated and compared with undoped TiO2/SiO2. The results showed that the photoresponse of Cu2+ and Zn2+ doped TiO2/SiO2 were larger than undoped TiO2/SiO2, indicating that the photogenerated carriers were separated more efficiently in Cu2+ and Zn2+ doped TiO2/SiO2. The reactivity was in the order of Cu2+ > Zn2+ > Ni2+ > Cr3+ > Co2+. The different photoreactivity was ascribed to combine effect of the different ionic radii and photocorrison tendency of the dopants. The sample was also characterized by surface analytical methods such as X-ray diffraction, scanning electron micrograph/electron dispersive X-ray analyzer and UV-Vis absorption spectrum. PMID- 24218856 TI - A high activity of Ti/SnO2-Sb electrode in the electrochemical degradation of 2,4 dichlorophenol in aqueous solution. AB - Electrochemical degradation of 2,4-dichlorophenol (2,4-DCP) in aqueous solution was investigated over Ti/SnO2-Sb anode. The factors influencing the degradation rate, such as applied current density (2-40 mA/cm2), pH (3-11) and initial concentration (5-200 mg/L) were evaluated. The degradation of 2,4-DCP followed apparent pseudo first-order kinetics. The degradation ratio on Ti/SnO2-Sb anode attained > 99.9% after 20 min of electrolysis at initial 5-200 mg/L concentrations at a constant current density of 30 mA/cm2 with a 10 mmol/L sodium sulphate (Na2SO4) supporting electrolyte solution. The results showed that 2,4 DCP (100 mg/L) degradation and total organic carbon (TOC) removal ratio achieved 99.9% and 92.8%, respectively, at the optimal conditions after 30 min electrolysis. Under this condition, the degradation rate constant (k) and the degradation half-life (t1/2) were 0.21 min- and (2.8 +/- 0.2) min, respectively. Mainly carboxylic acids (propanoic acid, maleic acid, propanedioic acid, acetic acid and oxalic acid) were detected as intermediates. The energy efficiencies for 2,4-DCP degradation (5-200 mg/L) with Ti/SnO2-Sb anode ranged from 0.672 to 1.602 g/kWh. The Ti/SnO2-Sb anode with a high activity to rapid organic oxidation could be employed to degrade chlorophenols, particularly 2,4-DCP in wastewater. PMID- 24218857 TI - Effects of rhamnolipid biosurfactant JBR425 and synthetic surfactant surfyno1465 on the peroxidase-catalyzed oxidation of 2-naphthol. AB - The kinetics of the recombinant Coprinus cinereus peroxidase-catalyzed 2-naphthol oxidation was investigated in the presence of rhamnolipid biosurfactant JBR425 and synthetic surfactant Surfynol465 at pH 5.5 and 250C, with concentrations of (bio)surfactants both less than critical micelle concentrations (CMC) and larger than CMC. It was shown that monomers of JBR425 as well as monomers of Surfynol465 had an enhancing effect on the conversion of 2-naphthol in dose response manner and did not influence the initial rate of 2-naphthol oxidation. The results were accounted by a scheme, which contains a stadium of enzyme inhibition by oligomeric 2-naphthol oxidation products. The action of the biosurfactant's (or synthetic surfactant's) monomers was explained by avoidance of the enzyme active center clothing with oligomers. Similar results have demonstrated the potential of rhamnolipid biosurfactant JBR425 due to its biodegradability. When biosurfactants' concentrations are larger than CMC, (bio)surfactants have an opposite effect on the oxidation of 2-naphthol by peroxidase. PMID- 24218858 TI - An novel identification method of the environmental risk sources for surface water pollution accidents in chemical industrial parks. AB - The chemical industry is a major source of various pollution accidents. Improving the management level of risk sources for pollution accidents has become an urgent demand for most industrialized countries. In pollution accidents, the released chemicals harm the receptors to some extent depending on their sensitivity or susceptibility. Therefore, identifying the potential risk sources from such a large number of chemical enterprises has become pressingly urgent. Based on the simulation of the whole accident process, a novel and expandable identification method for risk sources causing water pollution accidents is presented. The newly developed approach, by analyzing and stimulating the whole process of a pollution accident between sources and receptors, can be applied to identify risk sources, especially on the nationwide scale. Three major types of losses, such as social, economic and ecological losses, were normalized, analyzed and used for overall consequence modeling. A specific case study area, located in a chemical industry park (CIP) along the Yangtze River in Jiangsu Province, China, was selected to test the potential of the identification method. The results showed that there were four risk sources for pollution accidents in this CIP. Aniline leakage in the HS Chemical Plant would lead to the most serious impact on the surrounding water environment. This potential accident would severely damage the ecosystem up to 3.8 km downstream of Yangtze River, and lead to pollution over a distance stretching to 73.7 km downstream. The proposed method is easily extended to the nationwide identification of potential risk sources. PMID- 24218859 TI - Distribution and contamination status of chromium in surface sediments of northern Kaohsiung Harbor, Taiwan. AB - The distribution, enrichment, accumulation, and potential ecological risk of chromium (Cr) in the surface sediments of northern Kaohsiung Harbor, Taiwan, China were investigated. Sediment samples from ten locations located between the river mouths and harbor entrance of northern Kaohsiung Harbor were collected quarterly in 2011 and characterized for Cr, aluminum, water content, organic matter, total nitrogen, total phosphorous, total grease, and grain size. Results showed that the Cr concentrations varied from 27.0 to 361.9 mg/kg with an average of (113.5 +/- 87.0) mg/kg. High Cr concentration was observed near the Jen-Gen River mouth. The mean Cr concentration was high at 255.5 mg/kg, which was at least 2 to 7 times than that of other sites. This might imply significant Cr contribution from upstream receiving tanneries wastewater into the Jen-Gen River. The spatial distribution of Cr reveals relatively high in the river mouth region, especially in Jen-Gen River, and gradually diminishes toward the harbor entrance region. This indicates that the major sources of Cr pollution from upstream industrial and municipal wastewaters discharged along the river bank; and Cr may drift with sea current and be dispersed into open sea. Moreover, Cr concentrations correlated closely to the physical-chemical properties of the sediments, which suggested the influence of industrial and municipal wastewaters discharged from the neighboring industrial parks and river basins. Results from the enrichment factor and geo-accumulation index analyses imply that the Jen-Gen River sediments can be characterized as moderate enrichment and none to medium accumulation of Cr, respectively. However, results of potential ecological risk index indicate that the sediment has low ecological potential risk. The results can provide valuable information to developing future strategies for the management of river mouth and harbor. PMID- 24218860 TI - Historical trends in the anthropogenic heavy metal levels in the tidal flat sediments of Lianyungang, China. AB - The sedimentation of metals can preserve the historical record of contaminant input from local and regional sources and provide information on the historical changes in regional water and sediment quality. We report the 210Pb activities and the heavy metal (Cd, Cr, Cu, Mn, Pb and Zn) depth profiles from sediment cores retrieved in 2010. The mean sedimentation rates of 0.85-1.5 cm/yr are determined by 210Pb dating. The sediments in the tidal flat have recorded heavy metal deposition and thus allow the establishment of a connection between the temporal evolution of the heavy metal pollution and the historical changes in the economic development of Lianyungang. The enrichment factors (EF) are calculated to estimate the level of contamination stored in these sediments. The results show that in the studied sites, Cr and Cu display low EF values and are mainly from lithogenic origin. For the other studied trace metals, a great variability in the sedimentary record is observed. Significant anthropogenic enrichment over the last 50 years is revealed at the tidal flat that receives fluvial inputs. Zinc is the element with the highest EF values, followed by the order of Pb > Cd > Mn > Cu and Cr. The temporal variations of the heavy metals peak during the late 1980s to the early 2000s and show a decreasing trend afterward. The pollution intensity of the tidal flat is determined by using EF and the geo accumulation index (I(geo)), which show that, based on the l(geo) scale, the tidal flat of Haizhou Bay is unpolluted to moderately polluted. PMID- 24218861 TI - Heterogeneous fenton degradation of azo dyes catalyzed by modified polyacrylonitrile fiber fe complexes: QSPR (quantitative structure peorperty relationship) study. AB - The amidoximated polyacrylonitrile (PAN) fiber Fe complexes were prepared and used as the heterogeneous Fenton catalysts for the degradation of 28 anionic water soluble azo dyes in water under visible irradiation. The multiple linear regression (MLR) method was employed to develop the quantitative structure property relationship (QSPR) model equations for the decoloration and mineralization of azo dyes. Moreover, the predictive ability of the QSPR model equations was assessed using Leave-one-out (LOO) and cross-validation (CV) methods. Additionally, the effect of Fe content of catalyst and the sodium chloride in water on QSPR model equations were also investigated. The results indicated that the heterogeneous photo-Fenton degradation of the azo dyes with different structures was conducted in the presence of the amidoximated PAN fiber Fe complex. The QSPR model equations for the dye decoloration and mineralization were successfully developed using MLR technique. MW/S (molecular weight divided by the number of sulphonate groups) and NN=N (the number of azo linkage) are considered as the most important determining factor for the dye degradation and mineralization, and there is a significant negative correlation between MW/S or NN=N and degradation percentage or total organic carbon (TOC) removal. Moreover, LOO and CV analysis suggested that the obtained QSPR model equations have the better prediction ability. The variation in Fe content of catalyst and the addition of sodium chloride did not alter the nature of the QSPR model equations. PMID- 24218862 TI - Rehabilitation and improvement of Guilin urban water environment: function oriented management. AB - Economic development and population growth have deeply damaged the urban water environment of Guilin City, China. Main problems involved structural damage and functional deterioration of the urban waters. An integrated technical scheme was developed to rehabilitate the urban water environment and to enhance the waters' functions during 1998-2008. Improvement of waters' functions included water system reconstruction, water pollution control, water safety assurance, and aquatic ecological restoration. The water system was reconstructed to connect different waters and clean water supplies to the lakes. Moreover, water pollution was controlled to improve water quality by endogenous pollutant elimination and extraneous pollutant interception. In addition, ecological measures put in place serve to enhance water system functions and better benefit both nature and humans. The project has brought about sound ecological, economic and social benefits in Guilin City, which can potentially be extended to similar cities. PMID- 24218863 TI - Adsorption of Mn2+ from aqueous solution using Fe and Mn oxide-coated sand. AB - The adsorption of Mn2+ onto immobilized Mn-oxide and Fe-oxide adsorbent such as manganese oxide-coated sandl (MOCS1), manganese oxide-coated sand2 (MOCS2), iron oxide-coated sand2 (IOCS2), and manganese and iron oxide-coated sand (MIOCS) was investigated. The effects of pH (5.5 to 8.0) and temperature (25 to 45 degrees C) on the equilibrium capacity were examined. Equilibrium studies showed that there is a good fit with both Freundlich and Langmuir isotherm, which indicates surface heterogeneity and monolayer adsorption of the adsorbents. Kinetic data showed high correlation with the pseudo second-order model, which signifies a chemisorption-controlled mechanism. The activation energies, activation parameters (deltaG, deltaH, deltaS), and thermodynamic parameters (deltaG0, deltaH0, deltaS0) confirmed that adsorption with MIOCS was endothermic and more spontaneous at higher temperature while an opposite trend was observed for the other adsorbents. Thermodynamic studies showed that adsorption involved formation of activated complex, where MOCS 1 and MIOCS follow a physical-chemical mechanism, while MOCS2 and IOCS2 follows purely chemical mechanism. PMID- 24218864 TI - Degradation kinetics and mechanism of trace nitrobenzene by granular activated carbon enhanced microwave/hydrogen peroxide system. AB - The kinetics of the degradation of trace nitrobenzene (NB) by a granular activated carbon (GAC) enhanced microwave (MW)/hydrogen peroxide (H202) system was studied. Effects of pH, NB initial concentration and tert-butyl alcohol on the removal efficiency were examined. It was found that the reaction rate fits well to first-order reaction kinetics in the MW/GAC/H202 process. Moreover, GAC greatly enhanced the degradation rate of NB in water. Under a given condition (MW power 300 W, H202 dosage 10 mg/L, pH 6.85 and temperature (60 +/- 5)degrees C), the degradation rate of NB was 0.05214 min-1when 4 g/L GAC was added. In general, alkaline pH was better for NB degradation; however, the optimum pH was 8.0 in the tested pH value range of 4.0-12.0. At H202 dosage of 10 mg/L and GAC dosage of 4 g/L, the removal of NB was decreased with increasing initial concentrations of NB, indicating that a low initial concentration was beneficial for the degradation of NB. These results indicated that the MW/GAC/H202 process was effective for trace NB degradation in water. Gas chromatography-mass spectrometry analysis indicated that a hydroxyl radical addition reaction and dehydrogenation reaction enhanced NB degradation. PMID- 24218865 TI - Reflecting on our commitment to the future of nursing. PMID- 24218866 TI - Addressing the racial, ethnic and gender inequities in the childhood obesity crisis: a call to action. PMID- 24218867 TI - A cohort study evaluating the implications of biology, weight status and socioeconomic level on global self-esteem competence among female African American adolescents. AB - The link between obesity and self-esteem among minority youth has received minimal empirical evaluation. This study aims to describe the magnitude of risk that body mass index, household income, and transitional age have on global self esteem levels among African-American adolescents. These analyses were conducted on cross-sectional data obtained from 264 urban-dwelling African-American females between 14 and 18 years of age. Survey data on global self-esteem levels, transitory age, and socioeconomic levels were collected using self-administered questionnaires. Measured height and weight values were used to calculate and categorize weight status according to body mass index. Logistic regression models examined the probability of reporting less than average levels of global self esteem. Adolescent African-American females residing in low-income households were 10 times more likely to report lower global self-esteem scores than those individuals from more affluent households (95% CI: 1.94, 60.19, p < .001). Neither weight status (95% CI: 0.81, 2.55; p = .26) nor age (95% CI: 0.05, 1.87; p = .82) were significant risk indicators for lower than average levels of global self-esteem among participants in this study. Household income appears to be the greatest predictor of global self-esteem levels. Further research in this area is needed to fully elucidate precursors for psychological health vulnerability and facilitate intervention development. PMID- 24218868 TI - Decision-making about cervical cancer screening methods by homeless women. AB - To evaluate the perspectives and preferences of homeless women for traditional provider- and a novel low cost self-collected cytology screening technique, 17 interviews were conducted with women who participated in both phases of a comparative trial. Subjects were recruited from a comprehensive homeless service center and a residential program serving homeless women. Constructivist grounded theory guided data collection and analysis. Results showed self-collection was favored over provider-collected cytology, but that the women perceived that test accuracy trumped comfort. Although many women expressed inaccurate perceptions and beliefs about cervical cancer and screening, the women participated in and valued screening. Misconceptions about cervical malignancy and prevention strategies contributed to their complex appraisal of the two screening methods. Homeless women may partner with providers to develop and test effective interventions with high promise for improving their health and these insights may aid in developing effective interventions for diverse underserved communities. PMID- 24218869 TI - Reflections and perspectives of African-American community leaders regarding genetics and genomics research: sentiment and wisdom of Sankofa. AB - Advances in genetic and genomic research are shifting the typical disease timeline. For those afflicted by disease and for population groups known to experience excess disease-related morbidity and mortality, the ability to use genetics and genomics to predict an individuals' predisposition for developing a disease and/or to anticipate an individual's response to treatments holds tremendous promise. Over the past two decades several public and private institutions within the United States have been established for the purpose of collecting and storing biological specimens for the purpose of conducting genetic/genomic research. Multiple reports indicate that the involvement of racial/ethnic minority participants in these bio-repositories is limited. Little is known about the willingness of African-Americans, one of the largest and most vulnerable racial/ethnic population groups, to participate in genetic research, genomic research, and to contribute biological specimens to bio-repositories. An exploratory study was undertaken using principles of community engagement and community-based participatory research to examine the perspectives of leaders within the African-American community about participation in genetics research, genomics research, and bio-banking. Semi-structured focus groups with twenty-one African-American community leaders were the primary means of gathering the study data. Reflections and commentary of the community leaders were interspersed with sentiments of "Sankofa." The emergent themes, health-related disparities, historical injustices in medical research, the promise of genetic and genomic research, and genetics/genomic research engagement, implicated the importance of conducting genetics/genomics research in the context of the community interdependent with efforts to address determinants of health and health disparities. PMID- 24218870 TI - An evidence-based parenting intervention with inner-city teen mothers. AB - The consequences of teen pregnancy have a substantial negative impact on both the teen mother and her child. Recent evidence clearly supports parenting education as the most effective means for improving adolescent parenting skills. This study evaluated the effectiveness of a school-based program using an evidence-based educational intervention to improve parenting style in high school teen mothers. Teen mothers, from 15 to 18 years of age, in a Title 1 high school were recruited from the Early Head Start program. Two groups of teens (N = 10) completed a pre parenting style survey, enrolled in an 8- or 12-week group educational session, and completed a post-parenting style survey. While quantitative data did not yield a change in parenting style, qualitative findings highlighted a strong need for teens to "tell their story" and to share personal experiences related to parenting. These findings lend support for the role of parenting educational interventions in high schools with teens at high risk for pregnancy. PMID- 24218871 TI - Barriers to diagnosis and treatment of depression: voices from a rural African American faith community. AB - Mental health disparities exist for rural African-Americans regarding the early detection of depression and its effective treatment. Disparities that are evident in rural communities include limited mental health resources and the stigma of depression. The faith community has a long-standing history of being the initial source of help to those who experience depression. The purpose of this qualitative study was to examine how rural African-American faith communities view the barriers to diagnosis and treatment of depression. A convenience sample of 24 persons (N = 24) participated in focus groups and interviews. Four internal barriers were identified: personal business, "mindset," "denial," and "put on a front." Additionally,four external barriers were identified: "spiritual beliefs," "lack of medical resources," "lack of education about depression," and "stigma." The identified barriers supported the results from previous studies, but they also highlighted other less acknowledged barriers. In conclusion, interventions are needed to overcome these barriers in order to eliminate the depression disparities experienced by this population. PMID- 24218872 TI - Promoting breast health among urban African-American women: evidence supporting the need for a purposeful pursuit of the promise. AB - While several reports of studies undertaken to examine the influence of individual factors and access to quality care on the breast cancer outcomes of African-American women have been published, few studies have been reported that examined the interaction of these factors with variables associated with the social and physical environment. This report presents a summary of outcomes of a study undertaken to explore the impact of individual factors, social factors, environmental factors, and access to quality breast care on breast awareness and breast cancer screening practices among a targeted group of African-American urban women. The findings revealed that awareness and screening were significantly influenced by the participant's age, insurance status, characteristics of their social environment, and their breast awareness. The findings emphasize the need for targeted programming and services in low-income communities and inner-city neighborhoods where women may be less inclined to "venture out" and where clinicians, educators, researchers, and representatives of institutions dedicated to breast cancer control have been less inclined to "venture in." PMID- 24218873 TI - Increasing HIV/AIDS awareness among African-American women: an exploratory study. AB - This exploratory study was conducted to assess the effect of an HIV/AIDS prevention program on producing positive changing attitudes among African American women in Southeast Georgia. This study used a faith-based approach. Data were collected from 23 respondents recruited from a local African-American church. HIV training was conducted over four 1-hour sessions using web-based interactive videos and lectures on HIV/AIDS. Constructs from the Social Cognitive Theory comprised the framework upon which the women received HIV/AIDS prevention training. Participants completed a 25-item pre- and post-intervention questionnaire to measure any changes that occurred in their attitudes regarding HIV/AIDS. Results showed a statistically significant difference in mean scores of individual knowledge and attitudes about HIV. The difference in mean scores for the remaining items was found to be statistically insignificant. The overall change in attitudes was also statistically significant, t = 2.27, df = 22, p < 0.05, which provided further evidence that when peers educate their communities on HIV/AIDS, it makes a significant difference in changing their attitudes about this disease. Although findings were positive, further data is needed to substantiate and validate the use of community peers to increase knowledge and awareness about HIV/AIDS among the African-American population. PMID- 24218874 TI - [Effects of barley flake on metabolism of glucose and lipids in the patients with impaired fasting glucose]. AB - OBJECTIVE: To investigate the effects of barley flake (BF) on the glucose-lipid metabolism in patients with impaired fasting glucose (IFG). METHODS: 100 patients with IFG were divided into the oat meal (OM) control group and barley flake experimental group for three months intervention according to randomized controlled trail (RCT). Biochemical indicators, glucose-lipid metabolism related enzymes, the area under curve (AUC) of blood glucose and insulin after oral glucose tolerance test (OGTT) were assessed before and after intervention. In addition, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by FBG (mmol/L) x INS (microU/L)/ 22.5. RESULTS: At the end of the three month active intervention, the mean fasting blood glucose (FBG) and insulin (INS) in the patients with BF treatment decreased by 9.26% (P < 0.001) and 13.37% (P = 0.001) separately compared with that in patients with OM treatment; meanwhile, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in patients with BF treatment also decreased by 7.20% (P < 0.001) and 9.42% (P = 0. 002), respectively. Glycosylated hemoglobin (HbA1c), HOMA-IR, total glyceride (TG), Apo-B, the AUC of blood glucose and insulin after OGTT were also significantly decreased separately (P < 0.01 or < 0.05 ). However, statistically significant differences failed to be found in HDL-C, Apo-A, ALP and SOD between these two groups. CONCLUSION: BF had favorable effect on improvement of glucose lipid metabolism in the patients with impaired fasting glucose. PMID- 24218875 TI - [Prevalence of hyperlipidemia and possible risk factors in rural Chinese adults: cohort study of health population in Yuhuan rural]. AB - OBJECTIVE: To examine the prevalence of hyperlipidemia and its related factors in adults in rural Yuhuan, China. METHODS: A cross-sectional study was carried out as a baseline study of Rural Yuhuan Health Population Cohort in all communities in Yuhuan County, Zhejiang Province, China. A total of 118,571 subjects aged 35 years old or above participated in this study. The trained health/medical workers collected the general information, health conditions and so on by the face-to face interview. Totally, 5 ml blood samples were taken. Hyperlipidemia was defined as blood triglyceride > or = 1.70 mmol/L and/or total cholesterols > or = 5.18 mmol/L. SPSS 16.0 was used for statistical analysis. Data of the fifth China population census 2000 was used as the standard population. RESULTS: Among 118,571 eligible subjects, the averages of blood triglyceride and total cholesterols were (1.71 +/- 14.42) mmol/L and (5.48 +/- 40.25 ) mmol/L, respectively, and there was a statistical difference in gender on blood triglyceride (t = 4.163, P < 0.001) but not on blood total cholesterols. The crude prevalences of hyperchol-esterolemia, hypertriglyceridemia, both hypercholesterolemia and hypertriglyceridemia, and hyperlipidemia were 38.4%, 24.2%, 13.2% and 49.3% and the age-standardized prevalence were 36.6%, 23.8%, 12.7% and 47.7% based on 2000 China national population, respectively. These prevalences were higher in male than in female significantly and varied statistically over different age groups from the lowest group of 35-39 years old to highest group of 55-59 years old or 60-64 years old. A non-conditional binary logistic model showed that age, male, farmer, education levels, smoking, alcohol consumption and body mass index were significantly related to hyperlipidemia. CONCLUSION: Hyperlipidemia, especial hypercholesterolemia, was common in adults aged 35 years old or above living in rural China. PMID- 24218876 TI - [Non-linear canonical correlation analysis between anthropometric indicators and multiple metabolic abnormalities]. AB - OBJECTIVE: To define the general correlation between anthropometric indicators and multiple metabolic abnormalities, and to put forward some particular suggestions for the prevention of multiple metabolic abnormalities. METHODS: A random cluster sampling was carried out in one county of Henan Province. Questionnaire, physical examination and biochemical tests were admitted to the adult inhabitants. Non-linear canonical correlation analysis (NLCCA) was applied with OVERALS of SPSS 13.0. The coefficients of canonical correlation and multiple correlation were calculated. The plot of centroids labeled by variables showed the correlation among various indicators. RESULTS: In total, 2,914 objects were investigated. It included 1,134 (38.9%) males and 1,780 (61.1%) females (60.0%). The average age was (50.58 +/- 13.70) years old. The fitting result of NLCCA were as follows: the loss of 0.577 accounting for 28.8% of the total variation was relatively small, and indicated that the two sets of variables of this study, namely sets of biochemical indicators (including serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and fasting plasma glucose) and sets of others (including gender, BMI and waist circumference) were closely related and often changed synchronously. Multivariate correlation coefficient showed that internal indicators of the above two sets were closely related respectively and often showed the multiple anomalies of the same set. The diagram of the center of gravity of the association of various indicators showed that the symptoms of metabolic abnormalities increased with age. Women were more liable to have metabolic abnormalities. Overweight and obese people often suffer multiple metabolic disorders. Waist circumference was positively correlated with metabolic abnormalities. CONCLUSION: (1) Biochemical indicators and anthropometric often change in combination. (2) Much attention should be paid to older people especially middle-aged or older men and older women in primary prevention. (3) Overweight and abdominal obesity can be considered the sensitive predictive indicator of multiple metabolic abnormalities. (4) Nonlinear canonical correlation and center of gravity Figure had the advantage of analyze the correlation between multiple sets of variables. PMID- 24218877 TI - [Association between polymorphism of FOXA1 gene and type 2 diabetes]. AB - OBJECTIVE: To detect the relationship between FOXA1 gene polymorphism and type 2 diabetes mellitus (T2DM). METHODS: The techniques of mass chromatographic analysis were used to detect the polymorphism of FOXA1 gene in 190 patients with T2DM and 193 healthy control persons without T2DM. We used the software SPSS 13.0 for statistical analysis. RESULTS: There was no significant difference between the case and control group about sex and age distribution. The distribution of genotypic frequency in control group consistented with the Hardy-Weinberg law. The frequency of the TT, TC and CC genotype in case were 76.5%, 19.3% and 4.3%. The frequency of the TT, TC and CC genotype in control were 78.1%, 20.3% and 1.6%. There was no significant difference between the case and control group about genotype frequency (chi2 = 2.49, P = 0.287). There may be no significant difference between the TC, TG, HDL-C, LDL-C level and genotypes of rs7144658 in mutant. CONCLUSION: There may be no significant relationship between the polymorphism of FOXA1 gene and T2DM. Genic mutation on rs7144658 may not affect the lipid level in type 2 diabetics. PMID- 24218878 TI - [Removal of high-abundance proteins in plasma of the obese by improved TCA/acetone precipitation method]. AB - OBJECTIVE: To develop an improved trichloroacetic acid (TCA)/acetone precipitation method for removal of high-abundance proteins in plasma of the obese. METHODS: Volumes of TCA/acetone solution (1, 3, 4, 5, 6, 8, 10 and 20 times of the sample) and concentrations of TCA (10%, 30%, 50%, 60%, 70% TCA/acetone solution) have been investigated to optimize the conditions of sample preparation. SDS-PAGE were used to separate and tested proteins in the supernatant and sediment. The best concentration of the TCA/acetone solution was first determined by SDS-PAGE. The protein in precipitation from 10% TCA/acetone solution processing and the new determined concentration TCA/acetone solution processing were verified by 2-D-SDS-PAGE. And then the digested products of the protein in precipitation and supernatant by trypsin were analyzed by nano HPLC Chip-MS/MS to verify which is the best concentration to process the plasma. RESULTS: The best volume of TCA/acetone is four times to sample, which less or more TCA/acetone would reduce the removal efficiency of high-abundance proteins. The concentration of TCA in acetone solution should be 60%, which may remove more high-abundance proteins in plasma than 10%, 30%, 50% TCA in acetone solution. If the TCA concentration is more than 60%, the reproducibility will be much poorer due to fast precipitation of proteins. The results of mass identification showed that human plasma prepared with 60% TCA/acetone (4 times sample volume) could be verified more low-abundance proteins than 10%. CONCLUSION: The most desirable conditions for removal of high-abundance proteins in plasma is 60% TCA/acetone (4 times sample volume), especially for the plasma of obesity. PMID- 24218879 TI - [Effect of folate on the proliferation of human cervical cancer cell and relationship with HPV16]. AB - OBJECTIVE: To study the effect of different concentration of folate in vitro on the proliferation and apoptosis of C33A cell with HPV negative and CaSki cell with HPV16 positive, and intreaction of folate and HPV16. METHODS: C33A and Caski cells were intervened by different concentration of folate (0.1, 1.0, 10, 50, 100, 500, 1,000 and 2,000 microg/ml). The morphological changes of cells were examined by reverse discrepancy microscope. MTT and Flow Cytometry (FCM) were employed to measure the proliferation, inhibition ratio, cell cycle and apoptosis of cells. RT-PCR was used to detect the expression of HPV16 E2/E6 oncogene. RESULTS: The effects of folate on the C33A and CaSki cell growth suppression were increased gradually with the concentration of folate increasing and cultured duration prolonging, the inhibition ratio was increased (C33A: r = 0.948, P = 0.010; CaSki: r = 0.895, P = 0.006). Adding folate could induce cell apoptosis (C33A: r = 0.989, P < 0.001; CaSki: r =0.994, P < 0.001), and there was a linear relationship, but there was no significant difference on the proliferation and apoptosis of C33A and CaSki cells effected. In addition, concentration of folate did not affect the expression of HPV16 E2/E6. CONCLUSION: Different concentration of folate inhibited cervical cancer cell proliferation and enhanced cell apoptosis, but the results do not support an interaction between folate and HPV16 in cervical cancer cell. PMID- 24218880 TI - [Genetic damage in peripheral blood lymphocyte of 1,3-butadiene workers]. AB - OBJECTIVE: To investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to 1,3-butadiene (BD). METHODS: Personal information including occupational history, age, sex, smoking and drinking status was collected by the questionnaire. Gas chromatography was used to analyze the BD level. One hundred and eighty 1,3-butadiene workers and 58 controls without occupational BD exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. RESULTS: The concentration of BD in the working environment of BD-exposed workers was 1.80 (0.59-2.76) mg/m3. The rate of CBMN, NPB, NBUD and Olive TM of lymphocyte in BD exposed workers [(6.76 +/- 4.99) per thousand, 1.00 (0.00-4.00), 2.00 (0.00-7.00) and 4.64 (3.50-5.98), respectively] were higher than those in controls [(3.10 +/- 2.65) per thousdand, 0.00 (0.00-2.80), 1.00 (0.00- 5.00) and 2.34 (0.82-3.93), P < 0.01]. According to the length of work, 180 BD-exposed workers were classified into 3 groups: 1 yrs-, 14.0 yrs- and 20.0 yrs-group, respectively after adjusting the age,sex, smoking and drinking, the rate of CBMN was a rising tendency along with the increase in length of work. CONCLUSION: Under present BD exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect BD induced genotoxicity in BD-exposed workers, and are more suitable to assess the cumulative damage effect on DNA. PMID- 24218881 TI - [Effect of in utero and lactational exposure to a binary mixture of 3,3',4,4', 5 pentachlorobiphenyl (PCB126) and 2,3',4,4',5-pentachlorobiphenyl (PCB118) on reproductive function in male rat offsprings]. AB - OBJECTIVE: To examine the effects of in utero and lactational exposure to a binary mixture of 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3',4,4',5 pentachlorobiphenyl (PCB118) on reproductive function in male rat offsprings. METHODS: Pregnant Sprague-Dawley rats were given the mixture by gavage with 0.096, 0.96, 4.8 microg toxic equivalency (TEQ)/kg on gestational day (GD) 15. The effects of mixture on F1 rats were observed. RESULTS: The male offspring in the 0.96 and 4.8 microg TEQ/kg groups showed significant inhibition of body weight gain, anogenital distance (AGD) and sperm counts. Mixtures at 4.8 microg TEQ/kg significantly reduced weights of accessory sex organs, but only prostate weight reduced at 0.96 microg TEQ/kg. There were no significant differences on serum testosterone. CONCLUSION: The results demonstrated that in utero and lactational exposure to the mixtures of PCB126 and PCB118 affected development of male offspring and impaired adult male offspring reproductive organs. PMID- 24218882 TI - [Distribution of arsenic species and its DNA damage in subchronic arsenite exposed mice]. AB - OBJECTIVE: To study the arsenic distribution, speciation, its effects on the balance of other elements and the DNA damage by subchronic arsenite exposure in mice. METHODS: The 8-week-old C57BL/6N mice were matched by weight and divided into control group and supplementation group, which were given 0 or 10 microg/ml of sodium arsenite in the drinking water, and continuous exposed for 6 months. RESULTS: Arsenic was found in various tissues and organs. The highest ones were in the kidney, lung and liver, reached (563.9 +/- 222.5), (458.6 +/- 191.0) and (279.8 +/- 81.2) ng/g, respectively while the lowest in the blood and brain, reached (82.2 +/- 26.7) ng/ml and (101.8 +/- 30.1) ng/g, respectively. Arsenic exists mainly in the form of dimethylarsinous acid (DMA). Compared to the control group, there was a significant difference (P < 0.05) between arsenic and chromium, copper, zinc, selenium, lead in some organs of arsenic exposed group, but not cadmium. Furthermore, the 8-hydroxydeoxyguanosine (8-OHdG) level of the exposed group was (149.1 +/- 1.0) ng/ml, which was significantly higher than the control group of (76.4 +/- 27.9) ng/ml. CONCLUSION: Arsenic accumulated in various tissues and organs mainly in the form of DMA, which affected the balance of chromium, copper, zinc, selenium and lead in the body, and led to DNA damage after subchronic exposure. PMID- 24218883 TI - [Association research between polymorphism of IFN-gamma and IL-10, environmental risk factors, and susceptibility to esophageal cancer]. AB - OBJECTIVE: To explore the polymorphism of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) with susceptibility to esophageal cancer (EC), as well as the interaction between the environmental risk factors and the polymorphism of IFN-gamma or IL- 10. To explore the interaction between the polymorphism of IFN gamma and IL-10. METHODS: According to the case-control design, 120 EC cases and 122 controls were examined. PCR technology was used to determine the genotypes of IFN-gamma + A874T and IL-10 -A1082G. Indicators of quantitative analysis for interaction between IFN-gamma and IL-10, and parts of environmental factors were calculated by crossover analysis multiplicative mode. RESULTS: Allele frequencies of T of IFN-gamma + A874T was 37.92% in case group higher than 28.7% in control group (chi2 = 4.6414, P = 0.0312). Compared with IFN-gamma + 874AA genotype, OR of IFN-gamma + 874AT genotype was 1.729 (95% CI 1.015-2.947), OR of IFN-gamma + 874TT genotype was 2.923 (95% CI 1.227-5.214) and OR of IFN-gamma + 874AT + TT genotype was 1.821 (95% CI 1.081-3.069). There was synergistic action between IFN gamma + 874AT + TT and drink index, moldy food and regular diet habit, their S respectively were 1.909, 4.154 and 5.026. The interaction between IFN-gamma + 874AT + TT and IL-10 -1082AG + GG was not increased the risk of EC OR = 2.342 (95% CI 0.975-5.626). CONCLUSION: The IFN-gamma + 874AT genotype might be a risk factor to EC. T allele gene may be heredity predisposing gene of EC. IFN-gamma + 874 AT + TT genotype as the corresponding reduction of the environmental risk factors can reduce the incidence of esophageal cancer. PMID- 24218884 TI - [Profile of P66SHC expression and histone modifications in replicative cell senescence and oxidative-stress induced premature senescence]. AB - OBJECTIVE: To study the profile of P66SHc expression and histone modifications in replicatively senescenct cells and oxidative-stress inducing premature senescenct cells. METHODS: HPF cells were continuously cultured and subcultured in vitro to build replicative cellular model. HPF cells were treated with 200 pmol/L H2 O2 four times to build oxidative-stress inducing premature senescenct model. Comparative Q-PCR was utilized to investigate target gene (P66SHC, EP300, HDAC1) expressions respectively in H2O2 treated groups and normal cell groups. Then CHIP QPCR was conducted to analyze histone modifications of P66SHC between young cells and aging cells. RESULTS: P66SHC expression was positive correlation with H2O2 doses and population doubling level (PDL) (R = 0.909, P = 0.000; R = 0.743, P = 0.006), while EP300 was negative correlation with H2O2 (R = - 0.922, P = 0.000) and both EP300 and HDAC1 were negative with PDL (R = -0.709, P = 0.010, R = 0.599, P = 0.040). H3 histone modifications were declined in P66SHc gene regulating region. H3-Ac, H3K9-Ac and H3K4-tri-Me were dominant in the upstream region of transcriptional site (-3.0 kb) and alternative promotor (+3.8 kb). CONCLUSION: P66SHC, EP300 and HDAC1 probably play a role in cellular replicative senescence and oxidative-stress inducing premature senescence. Besides, histone modification could regulate P66SHC gene expression. PMID- 24218885 TI - [Depressive symptoms and its related factors among primary and middle school students in an urban-rural-integrated area of Chongqing]. AB - OBJECTIVE: To investigate the prevalence of depressive symptom and its influencing factors among primary and middle school students in urban-rural integrated area of Chongqing. METHODS: A total of 3 013 primary and middle school students from an urban-rural-integrated area of Chongqing were selected by using multistage stratified cluster sampling method in this study. The general information, physical activities and physical examination conditions were investigated. Meanwhile, the depress symptoms were assessed by using children's depression inventory (CDI) and the incidence of adolescence related events were evaluated by using pubertal development scale (PDS). Chi-square test was used to analyze the detection rate of depression symptoms among different population and Logistic regression was used to analyse the influencing factors of depressive symptoms among primary and middle school students. RESULTS: The detection rate of depressive symptoms was 20.1% (607/3013) totally, and it was gradually higher among the students with bad to good economic status (28.3%/18.4%/18.3%, chi2 = 28.415, P < 0.05). The students' detection rate of depression symptoms in different development level compared to companion by self image were 43.1%, 26.5%, 22.0% and 15.8% (chi2 = 79.621, P < 0.01). Among the senior school students, worse economic status, higher development level in self-evaluation, and no physical activities in a recent month (including physical training, aerobic exercise) were considered as the influencing factors of depressive symptoms. CONCLUSION: Focusing on the physical and mental health of growing children, establishing a good school environment and family environment, and strengthening physical activities will contribute to reducing the incidence of depressive symptoms. PMID- 24218886 TI - [Expert investigation on food safety standard system framework construction in China]. AB - OBJECTIVE: Through investigating food safety standard framework among food safety experts, to summarize the basic elements and principles of food safety standard system, and provide policy advices for food safety standards framework. METHODS: A survey was carried out among 415 experts from government, professional institutions and the food industry/enterprises using the National Food Safety Standard System Construction Consultation Questionnaire designed in the name of the Secretariat of National Food Safety Standard Committee. RESULTS: Experts have different advices in each group about the principles of food product standards, food additive product standards, food related product standards, hygienic practice, test methods. According to the results, the best solution not only may reflect experts awareness of the work of food safety standards situation, but also provide advices for setting and revision of food safety standards for the next. CONCLUSION: Through experts investigation, the framework and guiding principles of food safety standard had been built. PMID- 24218887 TI - [Prevalence survey of using characteristics of quality, quantity, origin and composition claims on food labels in China]. AB - OBJECTIVE: To understand the using characteristics of quality, quantity, origin and composition claims on food labels in China. METHODS: To get the label samples from different size of supermarket by taking photos in Beijing, and also samples were provided by provincial quality technical supervision, et al. Then extracted the claims from the label samples, classified the samples by determined food categories, and analyzed the using characteristics of these claims. RESULTS: The constituent ratio of quality, quantity, origin and composition claims were 29.48%, 2.24%, 29.21%, 31.81% among all the samples. The constituent ratio of snacks (16.11%) was maximum among all the samples using quality claims, and grain and its products (36.00%) for quantity claims, meat and meat products (22. 09%) for origin claims, snacks (27.04%) for composition claims. "Nature, Natural" (48.63%) was the most used claims among all the samples using quality claims, "Exaggerated capacity" (44.00%) was the most for quantity claims, "Product of , From, Manufactured in" (34.36%) was the most for origin claims, and "Pure, 100% , All" (38.03%) was the most for composition claims. CONCLUSION: The using of quality, quantity, origin, and composition claims is frequently on food labels in China, and a lot of studies should be taken on this field, government should also enact regulations to regulate the use of this claims. PMID- 24218888 TI - [Comparison and anylisis on national quality control examination results of pesticides residues in food in 2009 and 2011]. AB - OBJECTIVE: To find out and compare the professionals proficiency of monitoring and inspection agencies on pesticide residue in food, and identify the main factors affecting the quality of result to provide references for improving the quality of the monitoring and inspection results. METHODS: Compare the national quality control examination results of pesticides residues in food of 2009 with 2011. RESULTS: The submission rates of examination results in 2011 were much higher than in 2009. They were respectively 100% and 83.6%. With the exception of few pesticides, the qualitative qualification rate and quantitative satisfaction rate of other pesticides were also relatively higher, and the qualitative qualification rate and quantitative satisfaction rate in 2011 were all higher than the same examination pesticides in 2009. For instance, the qualitative qualification rate of chlorpyrifos were respectively 99.4% and 96.8% in 2011 and 2009. The qualitative qualification rate of triazophos were respectively 100% and 97.1% in 2011 and 2009. The quantitative satisfaction rate of chlorpyrifos were respectively 93.8% and 90.2% in 2011 and 2009. The quantitative satisfaction rate of triazophos were respectively 91.9% and 87.2% in 2011 and 2009. CONCLUSION: The general testing levels of monitoring and inspection agencies on pesticide residue in food were sufficient, and their testing proficiency increased year by year, but some institutions still need to improve the testing proficiency. PMID- 24218889 TI - [Study on predictive value of pulmonary ventilation function of healthy coal mine workers]. AB - OBJECTIVE: To establish the predictive value of pulmonary ventilation function for dust-exposed-workers in some coal mine. METHODS: From March to August in 2011, 2994 coal workers were involved in the research, their pulmonary ventilation function were examined by pulmonary function measuring instrument. 1389 worker's pulmonary ventilation function were normal, the data of 1139 workers established the predictive value equation, and those of 250 workers tested the equation. RESULTS: Age was negatively correlated with FVC, FEV1, FEV1%, MMF and PEFR (P < 0.05). Height was negatively correlated with FEV1%, however, it was positively correlated with others (P < 0.05). Weight was negatively correlated with MMF and positively correlated with FVC and PEFR (P < 0.05). The regression equation of the predictive value was established by age, height and weight as in dependent variables. It were above 90% that the accordance ratio to test the equation by original data and test data. Predictive value of pulmonary ventilatory function from predictive value equation were lower than that of lung fucntion machine (P < 0.05). CONCLUSION: Predictive value of pulmonary ventilatory function from predictive value equation was superior to that of lung fucntion machine. PMID- 24218890 TI - [Comparison of the effects between maize germ oil and lard oil loading on blood lipids and fatty acid profile of mice]. AB - OBJECTIVE: To investigate the changes in blood lipids and fatty acids profile of mice after different oil loading, and explore the effects of different dietary fatty acids on postprandial blood lipids and fatty acid profile. METHODS: Ninety six C57BL/6 mice were randomly divided into 2 groups by weight ,maize germ oil group and lard oil group. The mice were given maize germ oil or lard oil by gavage at a dose of 1 ml/100 mg BW, respectively, after over-night fasting. At 0, 30, 60, 120, 180 and 240 min after oil loading, 8 mice were selected randomly from both groups, respectively, and blood was collected via orbital bleeding for postprandial blood lipids and fatty acid profile analysis. RESULTS: The serum triglycerides and total free fatty acids levels in mice loaded with lard oil were significantly higher than those in mice loaded with maize germ oil, respectively, at 120, 180, 240 min. The serum saturated fatty acids and monounsaturated fatty acids in mice loaded with lard oil were significantly higher, whereas serum polyunsaturated fatty acids were significantly lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). Serum palmitic oil and oleic oil in mice loaded with lard oil were higher, whereas linoleic oil and arachidonic acid were lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). CONCLUSION: Compared with maize germ oil, lard oil leads to higher postprandial serum triglycerides and saturated fatty acids levels, that may increase the risk of cardiovascular diseases. PMID- 24218891 TI - [Multiple-locus variable number tandem repeat analysis of Staphylococcus aureus in one food poisoning case]. AB - OBJECTIVE: To type Staphylococcus aureus strains from a food poisoning case by MLVA method, detect staphylococcal enterotoxin, and provide lab evidence for molecular epidemiological study and analysis of evolution. METHODS: The genomic DNA of 10 stains in the food poisoning case were used as PCR template. Eight pairs of primers were selected from the MLVA database. The PCR method was carried out and the PCR products were analyzed by capillary electrophoresis. The results were analyzed by BioCalculator and compared with the MLVA database. The staphylococcal enterotoxin was detected with colloidal gold method. RESULTS: The 8 VNTR PCR products have no differernce in the 10 strains, the size of VNTR09_01, VNTR61_01, VNTR61_02, VNTR67_01, VNTR21_01, VNTR24_01, VNTR63_01 and VNTR81_01 are 373, 361, 328, 279, 845, 354, 394 and 658 bp, respectively. The 10 strains belong to the same MLVA type, which is a new MLVA type differnernt from other 3892 strains in MLVA database, the MLVA profile is 15-2-2-2-35-8-2-7. Meanwhile, the 10 strains have the same kind of staphylococcal enterotoxin, the are enterotoxin A and enterotoxin B. CONCLUSION: The 10 Staphylococcus aureus strains are of one MLVA type, and have the same characters of staphylococcal enterotoxin. They have high homology. PMID- 24218892 TI - [Observation on both Na(+)-K+ Atpase activity and expression of Na(+)-K+ AtPase alpha1 mRNA in lung tissues of rats acute poisoned with nickel carbonyl]. AB - OBJECTIVE: To examine the change of Na(+)-K+ ATPase activity and the expressions of Na(+)-K+ ATPase alpha1 mRNA in lung tissues of rats poisoned by nickel carbonyl and to discuss the mechanism of lung injury. METHODS: One hundred seventy healthy rats (85 male and 85 female) were exposed by inhalation of 20,135 and 250 mg/m3 nickel carbonyl for 30 min. Rats poisoned by chlorine gas with a concentration 250 mg/m3 served as positive group and healthy SD rats served as no treatment negative group. The rats were euthanized on 1, 2, 3 and 7 d after the administration of nickel carbonyl or chlorine gas. In various treatment groups, Na(+)-K+ ATPase activity was studied by colorimetric method and the expressions of Na(+)-K+ ATPase alpha1 mRNA were determined by RT-PCR. RESULTS: Na(+)-K+ ATPase activity and expressions of Na(+)-K+ ATPase alpha1 mRNA in lung tissues decreased in all treatment groups and chlorine gas-poisoned group, especially it was obvious decreased on the 2ed and 3rd day (P < 0.05). CONCLUSION: Nickel carbonyl could induce lung damage and decrease Na(+)-K+ ATPase activity and expressions of Na(+)-K+ ATPase alpha1 mRNA in lung. PMID- 24218893 TI - [Traffic-related PM2.5 regulates IL-2 releasing in Jurkat T cells by calcium signaling pathway]. AB - OBJECTIVE: To explore the effects of traffic-related PM2.5 on interleukin-2 (IL 2) in Jurkat T cells and the regulatory action of calcium signaling pathway. METHODS: The cells were exposed to 100 microg/ml of PM2.5 for 3, 6 and 24 h. Normal saline group, blank filter group, calcium chelating agent EGTA group and the calcineurin antagonist cyclosporine A (CSA) group were as parallel control. The level of IL-2 was detected by ELISA kits, the mRNA expression of CaN, NFAT were determined by QRT-PCR. The nuclear distribution of NFAT was observed by immunofluorescence microscopy. RESULTS: The level of IL-2 in Jurkat T cells exposed to 100 microg/ml PM2.5 was significantly lower than parallel groups, but higher than PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). With the increase of time, the releasing level of IL-2 appeared reducing trend in 100 microg/ml of PM2.5 group. The mRNA expression level of NFAT and CaN were higher than parallel groups, PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). PM2.5 can induce NFAT protein with dephosphorylation and be activated, and NFAT protein can shift into nuclear. The level of IL-2 was negatively associated with the expression level of NFAT and CaN gene (P < 0.05). CONCLUSION: Traffic-related PM2.5 may inhibit the releasing of IL-2, Ca(2+)-CaN-NFAT signal pathway may involve in the regulation of IL-2. PMID- 24218894 TI - [Determination of S-phenylmercapturic acid in urine by on-line enrichment liquid chromatography tandem mass spectrometry]. AB - OBJECTIVE: To develop on-line enrichment liquid chromatography tandem mass (LC MS/MS) method for determination of S-phenylmercapturic acid (S-PMA) in urine. METHODS: With d2-S-PMA added as internal standard, the urine samples were cleaned up and concentrated on Hypersil GOLD (20 mm x 2.1 mm x 12.0 microm) columns, and the targeted compounds were analyzed by HPLC-MS/MS under negative ion mode using Hypersil GOLD (50 mm x 2.1 mm x 3.0 microm) columns as analyzed columns. In the process of enrichment, the mobile phase is CH3OH: HCOOH (0.2%) = 5:95 (volume ratio), the flow rate is 1.50 ml/min. During the analysis, the mobile phase is CH3CN and HCOOH (0.2%) gradient elution, the flow rate is 350 microl/min. RESULTS: The linear range was 0-500 ng/ml. The related coefficient was 0.9986. The detection limit was 8.0 ng/ml. The recoveries were 78.2%-84.5%. The relative standard deviation was 1.49% (n = 5). CONCLUSION: The method uses internal standard method, it was used for determination of S-phenylmercapturic acid in the urine, sample don't need too much pretreatment, the sample volume to reduce, the organic solvent volume decrease. The method was simple, rapid, sensitive and accurate. It was for the detecting for S-phenylmercapturic acid in urine. PMID- 24218895 TI - [Discussion on barium sulfate turbidity as arbitration inspection method for sulfate in drinking water]. AB - OBJECTIVE: To evaluate the suitability of barium sulfate turbidity in Standard examination methods for drinking water (GB/T 5750.5-2006) as arbitration inspection method of sulfate in drinking water by evaluation of uncertainty. METHODS: The expanded uncertainty of determination result for the unknown water sample was given by evaluating all uncertainty components in process of determination of barium sulfate turbidity. RESULTS: The determination result of the unknown water sample is 250 mg/L , with the expanded uncertainty of 42 mg/L (kappa = 2). CONCLUSION: This method could not accurately determine the amount of sulfate which is close to health standard limited in drinking water, at the same time, it' s unsuitable as arbitration inspection method of sulfate in drinking water. Because the expanded uncertainty of determination results of the unknown water sample by barium sulfate turbidity is so big, with the confidence regions of sulfate of 208-292 mg/L. So, evaluating uncertainty of the determination results is helpful to choose the suitable arbitration inspection method. PMID- 24218896 TI - [Foodborne illness report systems in China]. AB - OBJECTIVE: To introduce the current foodborne illness report system in China. METHODS: Foodborne illness (food poisoning included) report system and food related unusual cases reported system were characterized by their report definitions, scopes and report procedures as well as their differences. RESULTS: From October, 2010 to June, 2012, there are 2961 centers of disease control and prevention and heath executive organizations at the different local levels registered in the foodborne illness (food poisoning included) report system and 1525 incidents were reported. There were 553 hospitals registered in the food related unusual cases reported system while only 38 cases reported. CONCLUSION: The foodborne illness report system has been set up in China and further efforts in capacities building are needed. PMID- 24218897 TI - [Suitability analysis of tolerance limit for aflatoxin M1 in foods and Chinese population dietary exposure to aflatoxin M1 from milk]. AB - OBJECTIVE: To assess the suitability of tolerance limit for aflatoxin M1 (AFM1) in foods and Chinese population dietary exposure to AFM1 from milk. METHODS: Milk and dairy products consumption data combined with the tolerance limit for AFM1 in foods as well as the concentration of AFM1 in milk were employed in assessment of both the intakes of AFM1 and the Chinese population long-time exposure to AFM1. AFM1 intake and the dietary exposure to projected risks for liver cancer attributable to either use of the maximum levels of AFM1 of 0.05 microg/kg milk or consumption of milk contaminated with AFM1 were assessed. RESULTS: Assuming that all milk and dairy products on sale contain AFM1 at the level equal to the tolerance limit of 0.5 microg/kg, the total average dietary exposure to AFM1 in Chinese population will be 0.20 ng per kilogram bodyweight per day, the increased risk of liver cancer in humans will be as 0.00062 cases per 100,000 individuals per year, if the incidence of HBs Ag carriers of 7.18% takes into account. As for the milk sample contaminated with AFM1 at the level of 1.2 microg/kg analyzed and issued by the General Adminstration of Quality Surpervision Inspection and Qarantine of China in 2011, the total average long-term exposure of the Chinese population to AFM1 from this milk sample will be 0.43 ng per kilogram bodyweight per day, the increased risk of liver cancer in humans might be 0.00133 cases per 100,000 individuals per year. CONCLUSION: The tolerance limit for AFM1 of 0.5 microg/kg implemented in China can effectively protect the whole population. In addition, although the health risk of short-term exposure to AFM1-contaminated milk is acceptable, the government still should take the effective measures to control the contamination of AFM1 in milk so as to reduce the Chinese long-time exposure to AFM1. PMID- 24218898 TI - [Acute risk assessment of cumulative dietary exposure to organophosphorus pesticide among people in Jiangsu province]. AB - OBJECTIVE: To understand the cumulative dietary exposure of Jiangsu residents to organophosphorus (OPs) pesticide and make acute risk assessment. METHODS: Integrated the data of the nutrition and health status of residents in Jiangsu and the data of monitoring of OPs pesticide in agricultural products. Chlorpyrifos was selected as index compound (index chemical, IC), then use relative potency factor (RPF) approach which commended by EPA and simple distribution evaluation. Caloulated the dietary cumulative exposure of OPs pesticide among Jiangsu residents and compared with acute reference dose (ARfD), then made risk assessment. RESULTS: The exposure of rural group of age 3-6 and 7 11 were 133.84 microg/kg BW and 154.32 microg/kg BW, exceeded ARfD. The exposure level of kids and elder was higher than adults. The exposure level of rural residents were higher than urban residents. The highest contribution to the food of each age group was greengrocery and leek. CONCLUSION: The average level of exposure was safety in Jiangsu, high exposure children were at acute poisoning risk. High contribution food such as greengrocery and leek should be strengthen monitoring. PMID- 24218899 TI - Improving the human-computer dialogue with increased temporal predictability. AB - OBJECTIVE: An experiment was conducted to investigate the impacts of length and variability of system response time (SRT) on user behavior and user experience (UX) in sequential computing tasks. BACKGROUND: Length is widely considered to be the most important aspect of SRTs in human-computer interaction. Research on temporal attention shows that humans adjust to temporal structures and that performance substantially improves with temporal predictability. METHOD: Participants performed a sequential task with simulated office software. Duration and variability, that is, the number of different SRTs, was manipulated. Lower variability came at the expense of on average higher durations. User response times, task execution times, and failure rates were measured to assess user performance. UX was measured with a questionnaire. RESULTS: A reduction in variability improved user performance significantly. Whereas task load and failure rates remained constant, responses were significantly faster. Although a reduction in variability came along with, on average, increased SRTs, no difference in UX was found. CONCLUSION: Considering SRT variability when designing software can yield considerable performance benefits for the users. Although reduced variability comes at the expense of overall longer SRTs, the interface is not subjectively evaluated to be less satisfactory or demanding. Time design should aim not only at reducing average SRT length but also at finding the optimum balance of length and variability. APPLICATION: Our findings can easily be applied in any user interface for sequential tasks. User performance can be improved without loss of satisfaction by selectively prolonging particular SRTs to reduce variability. PMID- 24218900 TI - Linear modeling of human hand-arm dynamics relevant to right-angle torque tool interaction. AB - OBJECTIVE: A new protocol was evaluated for identification of stiffness, mass, and damping parameters employing a linear model for human hand-arm dynamics relevant to right-angle torque tool use. BACKGROUND: Powered torque tools are widely used to tighten fasteners in manufacturing industries. While these tools increase accuracy and efficiency of tightening processes, operators are repetitively exposed to impulsive forces, posing risk of upper extremity musculoskeletal injury. METHODS: A novel testing apparatus was developed that closely mimics biomechanical exposure in torque tool operation. Forty experienced torque tool operators were tested with the apparatus to determine model parameters and validate the protocol for physical capacity assessment. RESULTS: A second-order hand-arm model with parameters extracted in the time domain met model accuracy criterion of 5% for time-to-peak displacement error in 93% of trials (vs. 75% for frequency domain). Average time-to-peak handle displacement and relative peak handle force errors were 0.69 ms and 0.21%, respectively. Model parameters were significantly affected by gender and working posture. CONCLUSION: Protocol and numerical calculation procedures provide an alternative method for assessing mechanical parameters relevant to right-angle torque tool use. The protocol more closely resembles tool use, and calculation procedures demonstrate better performance of parameter extraction using time domain system identification methods versus frequency domain. APPLICATION: Potential future applications include parameter identification for in situ torque tool operation and equipment development for human hand-arm dynamics simulation under impulsive forces that could be used for assessing torque tools based on factors relevant to operator health (handle dynamics and hand-arm reaction force). PMID- 24218901 TI - Variation in muscle activity among office workers when using different information technologies at work and away from work. AB - OBJECTIVE: To determine differences in muscle activity amplitudes and variation of amplitudes when using different information and communication technologies (ICT). BACKGROUND: Office workers use different ICT to perform tasks. Upper body musculoskeletal complaints are frequently reported by this occupational group. Increased muscle activity and insufficient variation are potential risk factors for musculoskeletal complaints. METHOD: Muscle activity of right and left upper trapezius and right wrist extensor muscle bundle (extensor carpi radialis longus and brevis) of 24 office workers (performing their usual tasks requiring different ICT at work and away from work) were measured continuously over 10 to 12 hours. Muscle activity variation was quantified using two indices, amplitude probability distribution function and exposure variation analysis. RESULTS: There was a trend for electronics-based New ICT tasks to involve less electromyography (EMG) variation than paper-based Old ICT tasks. Performing Combined ICT tasks (i.e., using paper- and electronics-based ICT simultaneously) resulted in the highest muscle activity levels and least variation; however, these Combined ICT tasks were rarely performed. Tasks involving no ICT (Non-ICT) had the greatest muscle activity variation. CONCLUSION: Office workers in this study used various ICT during tasks at work and away from work. The high EMG amplitudes and low variation observed when using Combined ICT may present the greatest risk for musculoskeletal complaints, and use of Combined ICT by workers should be kept low in office work. Breaking up combined, New, and Old ICT tasks, for example, by interspersing highly variable Non-ICT tasks into office workers' daily tasks, could increase overall muscle activity variation and reduce risk for musculoskeletal complaints. PMID- 24218902 TI - Energetic arousal and language: predictions from the computational theory of quantifiers processing. AB - OBJECTIVE: The author examines the relationship between energetic arousal (EA) and the processing of sentences containing natural-language quantifiers. BACKGROUND: Previous studies and theories have shown that energy may differentially affect various cognitive functions. Recent investigations devoted to quantifiers strongly support the theory that various types of quantifiers involve different cognitive functions in the sentence-picture verification task. METHOD: In the present study, 201 students were presented with a sentence-picture verification task consisting of simple propositions containing a quantifier that referred to the color of a car on display. Color pictures of cars accompanied the propositions. In addition, the level of participants' EA was measured before and after the verification task. RESULTS: It was found that EA and performance on proportional quantifiers (e.g., "More than half of the cars are red") are in an inverted U-shaped relationship. CONCLUSION: This result may be explained by the fact that proportional sentences engage working memory to a high degree, and previous models of EA-cognition associations have been based on the assumption that tasks that require parallel attentional and memory processes are best performed when energy is moderate. APPLICATION: The research described in the present article has several applications, as it shows the optimal human conditions for verbal comprehension. For instance, it may be important in workplace design to control the level of arousal experienced by office staff when work is mostly related to the processing of complex texts. Energy level may be influenced by many factors, such as noise, time of day, or thermal conditions. PMID- 24218903 TI - Dual-coded advisory turn indicators for GPS navigational guidance of surface vehicles: effects of map orientation. AB - OBJECTIVE: The aim of the study was to compare the decision times for left-right decisions for a dual-coded advisory turn indicator and a typical spatial-only turn indicator in a GPS navigational map display. BACKGROUND: Track-up maps are useful for turn decision making but do not facilitate configural knowledge acquisition of an area. North-up maps present a stable orientation for this type of learning, but typical implementations of north-up map displays lead to misaligned and confusing turn information. We compared a typical spatial-only indicator with a dual-coded spatial-plus-verbal indicator, systematically manipulating vehicle heading and measuring reaction time. The new display, the Dual-Coded Advisory Turn Indicator for Maps (DATIM), was based on an assumption of the advantages of concurrent verbal and spatial processing of advisory turn indicators in map displays. METHOD: The experimental design was a 2 x 2 x 24 mixed design with indicator type as a between-subjects factor and turn direction (left, right) and 24 heading angles (15 degrees intervals) as repeated-measures factors. Participants made turn decisions while viewing static displays of intersections at variably rotated headings. RESULTS: Reaction time for the DATIM display was consistently faster than the typical spatial-only indicator at all heading angles but especially at heading angles beyond +/- 45 degrees (520-ms difference at 180 degrees). CONCLUSION: The DATIM display produced faster turn decisions at all heading angles. APPLICATION: DATIM displays could allow north-up maps to be used for turn-by-turn decision making in GPS navigational systems. Drivers could have the advantages of both the stable orientation to facilitate planning and the easy turn-by-turn guidance. Limitations are discussed. PMID- 24218904 TI - Relative position vectors: an alternative approach to conflict detection in air traffic control. AB - OBJECTIVE: We explore whether the visual presentation of relative position vectors (RPVs) improves conflict detection in conditions representing some aspects of future airspace concepts. BACKGROUND: To help air traffic controllers manage increasing traffic, new tools and systems can automate more cognitively demanding processes, such as conflict detection. However, some studies reveal adverse effects of such tools, such as reduced situation awareness and increased workload. New displays are needed that help air traffic controllers handle increasing traffic loads. METHOD: A new display tool based on the display of RPVs, the Multi-Conflict Display (MCD), is evaluated in a series of simulated conflict detection tasks. The conflict detection performance of air traffic controllers with the MCD plus a conventional plan-view radar display is compared with their performance with a conventional plan-view radar display alone. RESULTS: Performance with the MCD plus radar was better than with radar alone in complex scenarios requiring controllers to find all actual or potential conflicts, especially when the number of aircraft on the screen was large. However performance with radar alone was better for static scenarios in which conflicts for a target aircraft, or target pair of aircraft, were the focus. CONCLUSION: Complementing the conventional plan-view display with an RPV display may help controllers detect conflicts more accurately with extremely high aircraft counts. APPLICATIONS: We provide an initial proof of concept that RPVs may be useful for supporting conflict detection in situations that are partially representative of conditions in which controllers will be working in the future. PMID- 24218905 TI - Coadaptive aiding and automation enhance operator performance. AB - OBJECTIVE: In this work, we expand on the theory of adaptive aiding by measuring the effectiveness of coadaptive aiding, wherein we explicitly allow for both system and user to adapt to each other. BACKGROUND: Adaptive aiding driven by psychophysiological monitoring has been demonstrated to be a highly effective means of controlling task allocation and system functioning. Psychophysiological monitoring is uniquely well suited for coadaptation, as malleable brain activity may be used as a continuous input to the adaptive system. METHOD: To establish the efficacy of the coadaptive system, physiological activation of adaptation was directly compared with manual activation or no activation of the same automation and cuing systems. We used interface adaptations and automation that are plausible for real-world operations, presented in the context of a multi-remotely piloted aircraft control simulation. Each participant completed 3 days of testing during 1 week. Performance was assessed via proportion of targets successfully engaged. RESULTS: In the first 2 days of testing, there were no significant differences in performance between the conditions. However, in the third session, physiological adaptation produced the highest performance. CONCLUSION: By extending the data collection across multiple days, we offered enough time and repeated experience for user adaptation as well as online system adaptation, hence demonstrating coadaptive aiding. APPLICATION: The results of this work may be employed to implement more effective adaptive workstations in a variety of work domains. PMID- 24218906 TI - Does elastic resistance affect finger pinch discrimination? AB - OBJECTIVE: The sensitivity of pinch movement discrimination between the thumb and index finger was assessed with and without elastic resistance. BACKGROUND: Researchers have examined the effect of elastic resistance on control of single upper-limb movements; however, no one has explored how elastic resistance affects proprioceptive acuity when using two digits simultaneously in a coordinated movement. METHOD: For this study, 16 right-handed, healthy young adults undertook an active finger pinch movement discrimination test for the right and left hands, with and without elastic resistance. We manipulated pinch movement distance by varying the size of the object that created the physical stop to end the pinch action. RESULTS: Adding elastic resistance from a spring to the thumb-index finger pinch task did not affect accuracy of pinch discrimination measured as either the just noticeable difference, F(1, 15) = 1.78, p = .20, or area under the curve, F(1, 15) = 0.07, p = .80. CONCLUSION: Having elastic resistance to generate lever return in pincers, tweezers, and surgical equipment or in virtual instruments is unlikely to affect pinch movement discrimination. APPLICATION: Elastic resistance did not affect finger pinch discrimination in the present study, suggesting that return tension on equipment lever arms has a practical but not perceptual function. An active finger pinch movement discrimination task, with or without elastic resistance, could be used for hand proprioceptive training and as a screening tool to identify those with aptitude or decrements in fine finger movement control. PMID- 24218907 TI - A three-component model of the control error in manual tracking of continuous random signals. AB - OBJECTIVE: The performance of human operators acting within closed-loop control systems is investigated in a classic tracking task. The dependence of the control error (tracking error) on the parameters display gain, k(display), and input signal frequency bandwidth, f(g), which alter task difficulty and presumably the control delay, is studied with the aim of functionally specifying it via a model. BACKGROUND: The human operator as an element of a cascaded human-machine control system (e.g., car driving or piloting an airplane) codetermines the overall system performance. Control performance of humans in continuous tracking has been described in earlier studies. METHOD: Using a handheld joystick, 10 participants tracked continuous random input signals. The parameters f(g) and k(display) were altered between experiments. RESULTS: Increased task difficulty promoted lengthened control delay and, consequently, increased control error.Tracking performance degraded profoundly with target deflection components above 1 Hz, confirming earlier reports. CONCLUSION: The control error is composed of a delay induced component, a demand-based component, and a novel component: a human tracking limit. Accordingly, a new model that allows concepts of the observed control error to be split into these three components is suggested. APPLICATION: To achieve optimal performance in control systems that include a human operator (e.g., vehicles, remote controlled rovers, crane control), (a) tasks should be kept as simple as possible to achieve shortest control delays, and (b) task components requiring higher-frequency (> 1 Hz) tracking actions should be avoided or automated by technical systems. PMID- 24218909 TI - [Medical research and the status of the embryo]. PMID- 24218908 TI - The impact of eye movements and cognitive workload on lateral position variability in driving. AB - OBJECTIVE: The objective of this work was to understand the relationship between eye movements and cognitive workload in maintaining lane position while driving. BACKGROUND: Recent findings in driving research have found that, paradoxically, increases in cognitive workload decrease lateral position variability. If people drive where they look and drivers look more centrally with increased cognitive workload, then one could explain the decreases in lateral position variability as a result of changes in lateral eye movements. In contrast, it is also possible that cognitive workload brings about these patterns regardless of changes in eye movements. METHOD: We conducted three experiments involving a fixed-base driving simulator to independently manipulate eye movements and cognitive workload. RESULTS: Results indicated that eye movements played a modest role in lateral position variability, whereas cognitive workload played a much more substantial role. CONCLUSIONS: Increases in cognitive workload decrease lane position variability independently from eye movements. These findings are discussed in terms of hierarchical control theory. APPLICATIONS: These findings could potentially be used to identify periods of high cognitive workload during driving. PMID- 24218910 TI - [Equity and access to care]. PMID- 24218911 TI - [Autonomy of the patient at the end of life and wish to die]. PMID- 24218912 TI - [Causes of pain in obstetrics]. AB - For women, the childbearing period is a source of pain related to dysmenorrhoea, childbirth, abortion, gynaecological diseases, etc. Physiologically, female sex hormones influence pain modulation. Whatever its cause, appropriate evaluation and treatment should be offered to relieve these women. PMID- 24218913 TI - [Evaluation and treatment of wound odour]. AB - Some wounds are foul-smelling; this may be temporary or continuous. Since the ability to perceive odour varies from one individual to another, it is complicated to evaluate and use this symptom for diagnostic purposes. Various conventional and alternative treatments can be offered but there is no single, universal solution. PMID- 24218914 TI - [Diabetes training in Mayotte]. AB - In 2012, the paramedical Francophone Diabetes Society (SFD) visited Mayotte in the context of a training programme for health professionals. The training addressed diabetes prevention, self-monitoring of blood glucose and treatment management while respecting the population's cultural habits. PMID- 24218915 TI - [Multidisciplinary and coordinated patient management]. PMID- 24218916 TI - [Epidemiology of multiple trauma]. AB - Whereas the number of serious accidents is decreasing in France, 50% of all people involved in traffic accidents are severely injured. They suffer from multiple injuries that require multi-disciplinary care. This real public health problem carries non-negligible human and financial costs for society. PMID- 24218917 TI - [Physiopathology of multiple trauma]. AB - Multiple trauma is a complex entity that can be life-threatening. It is essential to understand the links between injuries and intervene as quickly as possible to provide the cells with a constant and appropriate supply of oxygen in order to prevent irreversible damage. PMID- 24218918 TI - [Pre-hospital care for multi-trauma patients]. AB - To provide care for multi-trauma patients, prehospital teams need to act immediately, jointly and efficiently. Their objectives are to stabilise the patient's vital functions and identify injuries responsible for hemodynamic and/or respiratory failure. PMID- 24218919 TI - [Multi-trauma patients undergoing shock management]. AB - Multi-trauma patients need specific care provided by medical teams and hospitals with a technical platform that optimises emergency care.They also require a special 'shock management' unit with staff members available to welcome these patients and maintain their vital functions. PMID- 24218920 TI - [Care for multi-trauma patients, from the transfer to the operating theatre to intensive care]. AB - Nurses caring for multi-trauma patients returning from the operating theatre need to have extensive knowledge. Their role is to prevent and detect any complications, and namely respiratory and neurological complications, and act efficiently to keep the patient's condition from deteriorating. PMID- 24218921 TI - [Support for the families of multi-trauma patients in intensive care]. AB - Families are often in a state of shock when they learn that a loved one has been in an accident and been hospitalised in intensive care. The multi-disciplinary team works in synergy to welcome, inform, support and direct these families. PMID- 24218922 TI - [Facial trauma and multiple trauma]. AB - The human face contains the sense organs and is responsible for essential functions: swallowing, chewing, speech, breathing and communication. It is also and most importantly the seat of a person's identity. Multiple trauma adds a life threatening dimension to the physical and psychological impact of a facial trauma. PMID- 24218923 TI - [An interdisciplinary approach to benefit multi-trauma patients with psychiatric disorders]. AB - Care for multi-trauma patients with psychiatric disorders is specific and interdisciplinary. Reflection is required to offer care tailored to each patient's personality. Communication between caregivers is essential. PMID- 24218924 TI - [Work after brain damage: unpredictability of outcomes]. AB - The Unit for Evaluation, Re-Education and Socio-Professional Orientation (UEROS) is a bridge between the hospital environment and professional life. It assists brain-damaged patients with their social and professional reintegration while taking into account their specific needs. PMID- 24218925 TI - [Ethics and therapeutic advances in the field of prosthetics]. PMID- 24218926 TI - [Patients with multiple trauma. Bibliography]. PMID- 24218927 TI - [A tool for the management of patients with pulmonary embolism]. AB - In order to develop materials for the validation of skills in the pulmonology intensive care unit, a steering committee on 'Learning situations' was created in the University Hospitals Paris-West (Hupo-AP-HP). A tool was developed based on knowledge and skills to be validated by students in the event of pulmonary embolism. PMID- 24218928 TI - [Applying knowledge according to type of nursing care plan and clinical pathway]. PMID- 24218929 TI - Distribution and conservation of endangered Temoleh, Probarbus jullieni (Sauvage, 1880). AB - The freshwater fish, Probarbus jullieni (Sauvage), locally referred to as "Temoleh", is a high-valued freshwater fish in Malaysia and has both cultural and conservational significance. It is widely distributed in the North-east Asian countries such as Thailand, Cambodia, Vietnam and Malaysia. During the recent past, the natural stocks of P. jullieni have been decreased severely due to habitat degradation and man-induced hazards in aquatic ecosystem. Despite the vast research that has been conducted on various carp species, little attention has been given to P. jullieni. This study reviewed the published information on the status, distribution, reproduction and biodiversity of this commercially important fish species. The findings would greatly be helpful towards the species conservation and aquaculture development of the highly endangered P. jullieni. PMID- 24218930 TI - Horseshoe crab, Tachypleus gigas (Muller, 1785) spawning population at Balok Beach, Kuantan, Pahang, Malaysia. AB - Local and regional decline of Asian horseshoe crabs has spurred a study on its spawning population at Balok Beach, Kuantan, Pahang, Malaysia. This location was identified as spawning site due to the occurrence of horseshoe crab spawning pairs and nests. Size-frequency, length-weight relationships, sex ratio and epibiont infestation of Tachypleus gigas were studied. Instar stage was estimated based on prosomal width. Condition of the horseshoe crab carapace was reported. Visual search technique of horseshoe crab was conducted during high tide of new and full moons. Prosomal, opisthosomal and telson length and weight of each horseshoe crab were measured. Largest female was recorded with mean prosomal length and width of 154.4 and 246.9 mm, respectively. About 69.8% of the males belonged to size group of 151-200 mm and 53.3% of females were grouped into 201 250 mm. All individuals were of fourteenth to sixteenth instar stages. Sex ratio varied from 0.313 to 2.5 and attributed to commercial harvest and monsoon season. Sand sediment of study site showed 93% of fine sands with grain size ranged from 120 to 250 microm. Acorn and pedunculate barnacle, conical and flat slipper shells were found on the carapace of the specimens. Most males had damaged eyes and carapaces while females with broken telsons. Body damages of about 19.9% on the specimens were likely due to nearby fishing activities. Lack of satellite male indicated low spawning population. The finding of this study showed that the species is extremely threatened by human activities and coastal development. PMID- 24218931 TI - Azolla pinnata growth performance in different water sources. AB - Azolla pinnata R.Br. growth performance experiments in different water sources were conducted from May until July 2011 at Aquaculture Research Station, Puchong, Malaysia. Four types of water sources (waste water, drain water, paddy field water and distilled water) each with different nutrient contents were used to grow and evaluate the growth performance of A. pinnata. Four water sources with different nutrient contents; waste, drain, paddy and distilled water as control were used to evaluate the growth performance of A. pinnata. Generally, irrespective of the types of water sources there were increased in plant biomass from the initial biomass (e.g., after the first week; lowest 25.2% in distilled water to highest 133.3% in drain water) and the corresponding daily growth rate (3.61% in distilled water to 19.04% in drain water). The increased in biomass although fluctuated with time was consistently higher in drain water compared to increased in biomass for other water sources. Of the four water sources, drain water with relatively higher nitrate concentration (0.035 +/- 0.003 mg L(-l)) and nitrite (0.044 +/- 0.005 mg L(-1)) and with the available phosphate (0.032 +/- 0.006 mg L(-1)) initially provided the most favourable conditions for Azolla growth and propagation. Based on BVSTEP analysis (PRIMER v5), the results indicated that a combination of more than one nutrient or multiple nutrient contents explained the observed increased in biomass of A. pinnata grown in the different water sources. PMID- 24218932 TI - Analysis of Condition Index in Polymesoda expansa (Mousson 1849). AB - The Condition Index (CI) is a method to measure overall health of fish and that has been applied to estimate the effect that different environmental factors have on clam meat quality. The CI of local mangrove clam Polymesoda expansa in Kelulit, Miri Sarawak was determined from October 2010 to November 2011. Condition index that is generally used to characterize the physiological activity of organisms, varied from 1.8% in December 2010 to 3.4% in October 2011, with low values observed during the spawning period. The clam attained their best condition in quality of flesh weight during July-October. In present study, the CI showed a clear relationship with the reproductive cycle of P. expansa. However, no significant correlation (p > 0.05) was found between CI and the different physicochemical parameter of seawater. The data presented is necessary for developing sustainable management strategies and broodstock selection for the species which is crucial in aquaculture development. PMID- 24218933 TI - Large-scale culture of a tropical marine microalga Chaetoceros calcitrans (Paulsen) Takano 1968 at different temperatures using annular photobioreactors. AB - Outdoor mass culture of microalgae in the tropical area is important to minimize its production cost. This study evaluates the growth of Chaetoceros calcitrans in 120 L annular photobioreactors at indoor temperature (Treatment I, 25 +/- 2 degrees C) and outdoor tropical ambient temperature, (Treatment II, 30 +/- 6 degrees C). Each treatment was done in duplicates. For both treatments, C. calcitrans was first grown in starter columns of 10 L capacity for a period of 7 days at 25 +/- 2 degrees C. After 7 days, the 9 L culture was transferred to the annular photobioreactors and subsequently brought to a final volume of 100 L by adding 20 L fresh medium every 5 days. There was no significant difference (p > 0.05) in the dry weight of microalgae grown in natural light and those grown indoor. The results suggest that C. calcitrans can be grown in outdoor conditions, hence, saving time and microalgae production cost for the larviculture industry. PMID- 24218934 TI - Composition of macrobenthos in the Bakkhali channel system, Cox's Bazar with notes on soil parameter. AB - Macrobenthos in coastal environment that play a significant role in the food web. It could also use as a good indicator of aquatic ecosystem health. The abundance and composition of macrobenthos in Bakkhali channel system, Cox's Bazar were conducted in relation to the soil parameters. Samples were collected using Ekman Berge bottom grab from five different stations of Bakkhali channel. Macrobenthos were comprised of five major groups namely Polychaeta (9.96-30.31%), Oligochaeta (3.68-59.707%), Crustacea (0.02-58.40%), Bivalvia (1.40-82.09%) and Gastropoda (0.08-4.25%). Total number of macrobenthos was higher at station I (9000 individuals m(-2)) and station II (8517 individuals m(-2)) compared to other stations. Shannon diversity index among the stations ranged from 0.65-1.04. Soil pH and soil moisture ranged from 6.1-6.4 and 23.44-31.29%, respectively. The highest organic carbon concentration was observed at station I (2.11%) and lowest at station III (1.40%). Maximum fraction of sand by weight was found at stations II (81.88%) and III (87.88) while the highest fraction of clay (21.52%) and silt (8.0%) were recorded in station I. It was observed that benthic bivalves were positively correlated (r = 0.891, p > 0.05) with silt fraction of the sediments. PMID- 24218935 TI - Spatial distribution of copepods along the salinity gradient of Perai river estuary, Penang, Malaysia. AB - Investigation on copepod communities in Perai river estuary was conducted from November 2005 to May 2006. Five stations were established for monthly sampling and were located from the river mouth to the upper reaches of the river. Copepod samples were collected from vertical tows using a standard zooplankton net. The Perai river estuary was slightly stratified and salinity decreases significantly from the mouth of the river towards the upper reaches of the river. A total of 28 species of copepods were recorded and comprised of 14 families, Paracalanidae, Oithonidae, Corycaeidae, Acartiidae, Calanidae, Centropagidae, Eucalanidae, Pontellidae, Pseudodiaptomidae, Tortanidae, Ectinosomatidae, Euterpinidae, Clausidiidae and Cyclopidae. A total of 10 species showed high positive affiliation towards salinity (R > 0.60), Acartia spinicauda, Euterpina acutifrons, Microsetella norvegica, Oithona nana, Oithona simplex, Paracalanus crassirostris, Paracalanus elegans, Paracalanus parvus, Pseudodiaptomus sp. and Hemicyclops sp. The copepod species Pseudodiaptomus dauglishi were negatively affiliated towards salinity (R = -0.71). The copepod assemblages classified into two distinct groups according to salinity regimes, euryhaline-polyhaline group (25 marine affiliated species) and oligohaline-mesohaline group (3 freshwater affiliated species). PMID- 24218936 TI - Germination and seedling development of Trapa bispinosa Roxb. AB - Trapa bispinosa is a freshwater macrophyte occurring in stagnant or slow moving water streams. Information on assessment of seeds storage and germination of Trapa bispinosa is less available in literature. Dependence on fresh seeds abundance only from natural environment for plant propagation or cultivation may lead to insufficient supply of seeds due to various biotic and abiotic factors. This study evaluated the viability and germination of Trapa bispinosa seeds stored in zip-lock plastic bag at low temperature of 7 degrees C for six months and fresh seeds. In addition germinating seeds progressive development to juvenile plants was recorded and described. Experiments were conducted where stored and fresh seeds were soaked in 62 x 45 x 54 cm glass tanks filled with aged tap water to the level of 15 cm depth. Stored seeds showed low percentage germination of 2.82% compared to fresh seeds which was 71.19%. Eight distinct developmental stages were identified from germinating seeds to juvenile plants. Both stored and fresh seeds produced plants of similar morphology but stored seeds progressive development from germination, seedling to juvenile plants needed longer duration to achieve. The storage of seed at low temperature at 7 degrees C for six months showed reduced viability and also vigorousity. Improved methods should be developed for Trapa seeds storage taking into account of the seeds' endurance to dryness and moisture levels in order to maintained seeds viability for future uses either for production, research purposes or even conservation and restoration programs. PMID- 24218937 TI - [Androgen/androgen receptor directly regulates the expression of Caveolin-1 in mouse epididymides]. AB - OBJECTIVE: To investigate the mechanisms of androgen/androgen receptor (AR) regulating the expression of Caveolin-1 in the mouse epididymis. METHODS: The AR binding sites associated with the Caveolin-1 gene were identified by searching the database of genomewide AR binding sites in mouse epididymides obtained from chromatin immunoprecipitation-sequencing (ChIP-seq). Total RNA was extracted from the epididymal tissues of normal and castrated mice and those castrated but supplemented with testosterone propionate, and the expression of Caveolin-1 mRNA was detected by RT-PCR and RT-qPCR. ChIP was performed with AR antibodies, and ChIP-PCR and ChIP-qPCR were used to determine the in vivo AR occupancies on the two sites associated with Caveolin-1. RESULTS: Two AR binding sites associated with Caveolin-1 were found in the database, both located in the second intron region. After castration, the expression of Caveolin-1 was significantly increased, 1.8 +/- 0.17 times that of the control group (P < 0.05), and the fold enrichments of the two AR binding sites were dramatically reduced from 13.5 +/- 1.47 and 10.5 +/- 1.03 to 1.05 +/- 0.17 and 1.4 +/- 0.14, respectively (P < 0.01). After androgen supplement, however, the expression of Caveolin-1 was decreased to normal (P < 0.05), and the fold enrichments of the two AR binding sites significantly increased to 16.4 +/- 2.6 and 10 +/- 0.92, respectively (P < 0.01). CONCLUSION: Caveolin-1 is a bona fide AR direct target gene in the mouse epididymis, and its expression is negatively regulated by androgen. These findings have provided a new insight into the androgen/AR regulatory network in mouse epididymides. PMID- 24218938 TI - [Protective effect of pAdxsi-ERbeta adenovirus transfection on penile vascular endothelium in ERbetaKO mice]. AB - OBJECTIVE: To investigate the effect of the overexpression of the ERbeta gene on the penile vascular endothelium of ERbeta knockout (ERbetaKO) mice and its molecular mechanisms. METHODS: We randomly divided 12 ERbetaKO male mice into groups A (ERbetaKO + TNFalpha + pAdxsi-ERbeta) and B (ERbetaKO + TNFalpha + empty virus), the former treated by pAdxsi-ERbeta adenovirus transfection, the latter with empty virus, and meanwhile both injected intraperitoneally with TNFalpha at 6 microg per kg body weight per d for 14 days. Then we observed the erectile function of the mice by APO, determined the changes of the endothelial markers CD34 and vWF by immunohistochemical staining, and detected the expressions of the relevant molecules in the eNOS-NO pathway by RT-PCR, Western blot and immunohistochemistry. RESULTS: Compared with group B, group A showed a significantly increased number of penile erections (0.50 +/- 0.55 vs 2.17 +/- 0.41, P < 0.05), shortened erectile latency ([28.83 +/- 1.33] min vs [24.00 +/- 1.27] min, P < 0.05), enriched CD34 and vWF markers (0.67 +/- 0.52 vs 1.50 +/- 0.55 and 0.50 +/- 0.55 vs 1.33 +/- 0.52, both P < 0.05), elevated expressions of eNOS and Cam (RT-PCR: 1.38 +/- 0.03 vs 1.62 +/- 0.05 and 1.02 +/- 0.09 vs 1.42 +/ 0.05, both P < 0.05; Western blot: 1.27 +/- 0.04 vs 1.55 +/- 0.07 and 0.76 +/- 0.05 vs 0.95 +/- 0.08, both P < 0.05), and reduced expression of caveolin-1 (RT PCR: 2.13 +/- 0.13 vs 1.72 +/- 0.08, P < 0.05; Western blot: 3.99 +/- 0.16 vs 3.40 +/- 0.14, P < 0.05). The results of RT-PCR were consistent with those of Western blot. CONCLUSION: The ERbeta gene protects the penile vascular endothelium via the eNOS-NO pathway. PMID- 24218939 TI - [Progesterone induction keeps a balanced mitochondrial activity and a low ROS productivity in human sperm]. AB - OBJECTIVE: To observe the relative activity of sperm mitochondria and the proportion of ROS-positive sperm before and after capacitation and progesterone (Pg)-induced hyperactivation, and investigate the functional characteristics of sperm mitochondria. METHODS: We collected 20 samples of normal human spermatozoa that met the criteria of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th ed) and cultured them with the swim-up method in a CO2 incubator at 37 degrees C for 1 hour. We divided the sperm into a pre capacitation and a capacitated group, and further incubated the capacitated sperm in an upright tube with (Pg-induced group) or without (control group) slow releasing Pg at 37 degrees C for another hour. Then we determined the relative activity of mitochondria and the percentage of ROS-positive cells in the sperm samples using JC-1 and DCF staining. RESULTS: The relative activities of mitochondria were significantly increased in the capacitated, control and Pg induced groups (6.23, 14.36 and 12.33) as compared with the pre-capacitation group (1.42) (P < 0.05), while the percentages of balanced mitochondria (mitochondria with equal amount of high and low electric potentials) remarkably reduced (4.27%, 5.03% and 8.57% vs 21.64%, P < 0.05). The percentages of ROS positive sperm in the pre-capacitation, capacitated, control and Pg-induced groups were 2.89%, 0.70%, 4.25% and 1.90%, respectively, significantly lower in the capacitated than in the pre-capacitation group (P < 0.01), but dramatically increased in the control group after another hour of swim-up incubation and markedly higher than in the Pg-induced group (P < 0.01). CONCLUSION: Progesterone induction can hyperactive human sperm motility, inhibit the relative activity of mitochondria, keep mitochondria potential at a more balanced level, and reduce the production of ROS, which may help to raise the rate of in vitro fertilization and improve the quality of embryos. PMID- 24218940 TI - [Pre-freezing equilibration improves post-thaw human semen parameters]. AB - OBJECTIVE: To investigate the effect of pre-freezing equilibration on the cryo survival of human sperm and to optimize the protocol of direct fumigation for the freeze-thawing of human sperm. METHODS: We collected 50 semen samples from healthy donors, each subjected to cryopreservation with 3 different methods: non equilibration freezing (Group A), 10-min equilibration at room temperature before freezing (Group B), and 10-min equilibration at 4 degrees C before freezing (Group C). We examined all the post-thaw semen samples by computer-assisted semen analysis for the sperm motility parameters, and detected the sperm vitality and deformity index (SDI). RESULTS: The recovery rate of progressive sperm motility was (61.88 +/- 16.94)% in Group C, remarkably higher than in A ([48.61 +/- 16.44]%) and B ([49.41 +/- 13.77]%) (P < 0.05), but with no significant difference between the latter two. And there were no significant differences in sperm vitality and SDI among the three groups. CONCLUSION: Ten-minute equilibration at 4 degrees C before freezing can evidently improve the progressive motility of sperm in addition to its advantages of easy operation and controllable experimental condition. PMID- 24218941 TI - [Y chromosome microdeletions, chromosome karyotypes and reproductive hormones in patients with azoospermia and severe oligozoospermia]. AB - OBJECTIVE: To study the correlation of azoospermia and severe oligozoospermia with Y chromosome microdeletions, chromosome karyotype and reproductive hormones in male infertility patients. METHODS: We collected semen samples from 63 patients with azoospermia, 49 with severe oligozoospermia and 60 men with normal semen parameters, and determined the incidence of Y chromosome microdeletions, chromosome karyotypes and the levels of reproductive hormones. RESULTS: The incidence rate of Y chromosome microdeletions was 11.11% in the azoospermia and 8.16% in the severe oligozoospermia patients, as compared with 0 in the normal controls (P<0.05). The rate of chromosome abnormalities was 9.52% in the azoospermia group, with statistically significant differences from the severe oligozoospermia and normal control men (both 0) (P<0.05). The levels of FSH and LH were significantly higher in the azoospermia ([20.41 +/- 19.34] IU/L and [11.44 +/- 9.48] IU/L) and the severe oligozoospermia patients ([8.88 +/- 7.04] IU/L and [6.78 +/- 3.85] IU/L) than in the normal males ([3.88 +/- 2.21] IU/L and [4.63 +/- 1.51] IU/L) (P<0.05). CONCLUSION: Examinations of genetics and reproductive hormones are necessary for infertile males with azoospermia and severe oligozoospermia, which may contribute to early diagnosis and treatment. PMID- 24218942 TI - [Effects of hepatitis B virus on human semen parameters and sperm DNA integrity]. AB - OBJECTIVE: To investigate the effects of hepatitis B virus (HBV) in semen on human semen parameters and sperm DNA integrity. METHODS: We detected HBV DNA in the semen samples of 153 HBsAg-seropositive patients by real-time fluorescence quantitative PCR and calculated the sperm nuclear DNA fragmentation index (DFI) by sperm chromatin dispersion (SCD) assay. We compared the semen parameters between the HBV DNA-positive group (A, n = 43) and HBV DNA-negative group (B, n = 110) and analyzed the correlation of sperm DFI with the number of HBV DNA copies in the semen. RESULTS: HBV DNA was detected in 43 (28.1%) of the 153 semen samples. No statistically significant differences were observed in age, semen volume and sperm concentration between groups A and B (P >0.05). Compared with group B, group A showed significantly decreased sperm viability ([58.0 +/- 18.8]% vs [51.4 +/-17.1]%, P<0.05), progressively motile sperm ([29.6 +/- 13.3]% vs [24.5 +/- 10.1]%, P<0.05), average straight-line velocity ([23.7 +/- 4.0] microm/s vs [19.9 +/- 4.5 ] microm/s, P<0.01) and average path velocity ([26.5 +/ 7.0] microm/s vs [23.4 +/- 5.3] microm/s, P<0.01), but remarkably decreased sperm DFI ([19.3 +/- 8.0]% vs [24.2 +/- 9.4]%, P<0.01). The number of HBV DNA copies in semen exhibited a significant positive correlation with sperm DFI (r = 0.819, P < 0.01). CONCLUSION: HBV DNA in semen is not significantly associated with the number of sperm, but may affect sperm viability, velocity and DFI. There is a load-effect relationship between the number of HBV DNA copies in semen and sperm nuclear DNA integrity. PMID- 24218943 TI - [The value of histopathologic examination of testis tissue from testicular sperm aspiration]. AB - OBJECTIVE: To evaluate histopathologic examination of the testis tissue from testicular sperm aspiration (TESA). METHODS: We analyzed the results of inverted microscopy and histopathologic examination of 96 samples of testis tissue from TESA, and compared the accuracy of the two methods in detecting sperm in the testis tissue. RESULTS: Among the 11 cases in which sperm was found by inverted microscopy, 9 were confirmed by histopathologic examination, and among the 57 cases in which sperm was not detected by inverted microscopy, 11 (19.3%) were found with sperm by histopathologic examination. Histopathologically, the cases in which sperm was not found by inverted microscopy included Sertoli-cell-only syndrome (n = 34), maturation arrest (n = 12) and hypospermatogenesis (n = 11). CONCLUSION: Histopathologic examination may reveal sperm in the TESA testis tissue proved to be sperm-absent by microscopy, and thus offer valuable information for a second testicular sperm retrieval. PMID- 24218944 TI - [Bulky DNA adducts in human sperm correlate with semen parameters and sperm apoptosis]. AB - OBJECTIVE: To explore the correlation of sperm polycyclic aromatic hydrocarbons (PAH)-DNA adducts with semen quality and sperm apoptosis. METHODS: We collected semen samples from 433 infertile Chinese men, detected sperm PAH-DNA adducts using immunofluorescence staining and flow cytometry, and determined the rate of sperm apoptosis by TUNEL. RESULTS: Multiple linear regression analysis showed that the level of sperm PAH-DNA adducts was correlated negatively with sperm concentration (beta = -0.632), total sperm count (beta = -0.830) and sperm motility (beta = -9.647), but positively with the rate of sperm apoptosis (beta = 0.130). CONCLUSION: Sperm PAH-DNA adducts are evidently correlated with semen quality and sperm apoptosis, and play an important role in the evaluation of male productivity. PMID- 24218945 TI - [Impact of chronic prostatitis/chronic pelvic pain syndrome on sperm DNA fragmentation and nucleoprotein transition]. AB - OBJECTIVE: To investigate the impact of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on sperm DNA fragmentation and nucleoprotein transition. METHODS: Based on the recommended methods in the WHO Laboratory Manual for the Examination and Processing of Human Semen (5th ed), we conducted routine semen analysis for 65 CP/CPPS patients and 30 healthy men. We also analyzed the results of papanicolaou staining, sperm DNA fragmentation and sperm nucleoprotein transition. RESULTS: Compared with the healthy control males, the CP/CPPS patients showed significant decreases in sperm concentration ([134.05 +/- 99.80] vs [94.75 +/- 92.07]) x 10(6)/ml, P <0.05), the percentage of morphologically normal sperm ([7.26 +/- 2.28] vs [5.61 +/- 3.40]%, P <0.05) and sperm progressive motility ([59.18 +/- 16.06] vs [47.68 +/- 17.62]%, P<0.05), but dramatic increases in sperm DNA fragmentation ([22.92 +/- 11.51] vs [43.58 +/- 17.07%, P<0.01) and sperm nucleoprotein transition ([23.26 +/- 5.97] vs [32.14 +/- 8.79]%, P<0.01). CONCLUSION: CP/CPPS significantly reduces sperm quality and male fertility. PMID- 24218946 TI - [Pathogens of prostatitis and their drug resistance: an epidemiological survey]. AB - OBJECTIVE: To investigate the epidemiological features of the pathogens responsible for prostatitis in the Changshu area, and offer some evidence for the clinical treatment of prostatitis. METHODS: This study included 2 306 cases of prostatitis that were all clinically confirmed and subjected to pathogenic examinations in 3 hospitals of Changshu area from 2008 to 2012. Neisseria gonorrhoeae, mycoplasma urealyticum and chlamydia trachomatis were detected by nucleic acid amplification ABI 7500, the bacterial data analyzed by VITEK-2 Compact, the drug-resistance to antibacterial agents determined using the WHONET 5.6 software, and the enumeration data processed by chi-square test and curvilinear regression analysis using SPSS 19.0. RESULTS: The main pathogens responsible for prostatitis were found to be Staphylococcus haemolyticus (30%), Staphylococcus epidermidis (12%), Enterococcus faecalis (9%), Escherichia coli (6%), Staphylococcus warneri and Staphylococcus aureus (3%), Mycoplasma urealyticum (8%), chlamydia trachomatis (5%) and Neisseria gonorrhoeae (6%). Statistically significant increases were observed in the detection rates of Escherichia coli (chi2 = 17.56, P<0.05), Mycoplasma urealyticum (chi2 = 8.73, P<0.05), Chlamydia trachomatis (chi2 = 8.73, P<0.05) and Enterococcus (chi2 = 8.22, P<0.05), but not in other pathogens. The resistance rates of Gram-positive bacteria to erythromycin and benzylpenicillin G were both above 45%, but with no significant difference between the two, those of Oxacillin (chi2 = 10.06, P<0.05) and Cefoxitin (chi2 = 9.89, P<0.05) were markedly increased, but those of quinolones, gentamycin and clindamycin remained low, except rifampicin (chi2 = 11.09, P<0.05). The resistance rates of Gram-negative bacteria to cefazolin and ampicillin were relatively high (mean 57.3%), and those to ceftriaxone (chi2 = 11.26, P<0.05) and trimethoprim sulfamethoxazole (chi2 =11.00, P< 0.05) significantly high; those to amikacin, cefepime, piperacillin/tazobactam and imipenem remained at low levels with no significant changes. However, the resistance rates of mycoplasma urealyticum to ciprofloxacin (chi2 = 11.18, P<0.05) and azithromycin (chi2 = 9.89, P<0.05) were remarkably increased. CONCLUSION: Gram-positive bacteria are the major pathogens responsible for prostatitis, but Escherichia coli, enterococcus and sexually transmitted disease pathogens are found to be involved in recent years. Quinolones and aminoglycosides are generally accepted as the main agents for the treatment of Gram-positive bacterial infection. However, rational medication for prostatitis should be based on the results of pathogen isolation and drug sensitivity tests in a specific area. PMID- 24218947 TI - [Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia]. AB - OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP. PMID- 24218948 TI - [Modified Mathieu urethroplasty for failed hypospadias repair]. AB - OBJECTIVE: To review the indications, techniques and complications of reoperation for failed hypospadias repair using modified Mathieu urethroplasty. METHODS: Using modified Mathieu urethroplasty, we treated 24 hypospadias patients aged 3 12 (mean 4.5) years for whom the first (n = 20) or the second hypospadias repair (n = 4) had failed, including 13 cases of large coronary sulcus urethrocutaneous fistula, 5 cases of urethral meatus retraction and 6 cases of anterior urethra dehiscence. The modified procedure involved median longitudinal incision of the urethral posterior wall, dorsal tunica albuginea plication under the vascular and nerve bundle, and double dartos flap protection of the neourethra. RESULTS: Of the 24 patients, 19 (79.2%) were successfully treated by the first operation, which achieved desirable straightness, good cosmetic appearance and normal urethral meatus of the penis, without postoperative complications. Small urethrocutaneous fistula developed in 4 cases, of which 3 were cured by fistula repair and 1 self-healed. Urethral meatus stenosis occurred in 1 case, which was restored by meatal dilation. Urethrocele and urethrostenosis were not found in any of the cases. Two cases received urethroscopy postoperatively, which revealed no hypertrophic cicatrix at the site of median longitudinal incision in the urethral posterior wall. CONCLUSION: Modified Mathieu urethroplasty can be applied to hypospadias reoperation, particularly in such cases as large coronary sulcus urethrocutaneous fistula, urethral meatus retraction and anterior urethra dehiscence. The modified procedure includes median longitudinal incision of the urethral posterior wall, dorsal tunica albuginea plication under the vascular and nerve bundle, and double dartos flap protection of the neourethra. PMID- 24218949 TI - [Application of tunica dartos flap coverage to tubularized incised plate urethroplasty]. AB - OBJECTIVE: To investigate the application of tunica dartos flap coverage to the prevention of urinary fistula in tubularized incised plate (TIP) urethroplasty. METHODS: This study included 140 cases of hypospadias following TIP urethroplasty, aged 1.9-22 (mean 5.6) years. Of the total number, 85 cases of the distal type were treated by coverage of the neourethra with the longitudinal ventrolateral pedicled-dartos penile skin flap, while the other 55 cases of the proximal type with the pedicled-dartos flap of arteriae scrotales anteriories. RESULTS: Urethrocutaneous fistula occurred in 12 of the patients, including 7 cases of distal and 6 cases of proximal hypospadias. CONCLUSION: For distal hypospadias, the longitudinal ventrolateral pedicled-dartos penile skin flap can be used, while for proximal urethroplasty, the pedicled-dartos flap of arteriae scrotales anteriories can be applied in coverage of the neourethra, which can effectively reduce the incidence of fistula. PMID- 24218950 TI - [Comparison of 3 microsurgical approaches to the treatment of varicocele: report of 120 cases]. AB - OBJECTIVE: To compare the outcomes of the three microsurgical strategies, inguinal high ligation (IHL), retroperitoneal high ligation (RHL) and low ligation (LL) of internal spermatic veins, in the treatment of varicocele. METHODS: We retrospectively analyzed 120 cases of varicocele, which were equally divided into groups I , II and III to be treated by IHL, RHL and LL of internal spermatic veins, respectively. We compared the operation times, post-operative complications, recurrence rates and results of pre- and post-operation semen analysis among the three groups. RESULTS: The mean operation time was significantly longer in group III ( [55 +/- 6 ] min) than in I ([35 +/- 10] min) and II ([42 +/- 12] min) (P<0.05), while the rate of post-operative complications remarkably higher in group I (4 cases of hydrocele [10% ] and 3 cases of epididymitis [7.5%]) than in II (2 cases of hydrocele [5%] and 2 cases of epididymitis [5%]) and III (1 case of hydrocele [2.5%] and 1 case of epididymitis [2.5%]) (P<0.05). Six to 12 (mean 9) months of follow-up visit found 2 cases (5% ) of recurrence in group I, 1 case (2.5%) in group II and none in group III, with no statistically significant difference among the three groups (P>0.05). At 12 months after surgery, group III showed significantly higher sperm concentration, grade a +b sperm and the sperm motility than the other two (P<0.05), but no significant differences were observed in these parameters among the three groups preoperatively. CONCLUSION: As a microsurgical approach to the treatment of varicocele, LL is better than IHL and RHL of internal spermatic veins in improving the seminal parameters of the patients. PMID- 24218951 TI - [Shang Ring circumcision versus conventional circumcision for redundant prepuce or phimosis: a meta analysis]. AB - OBJECTIVE: To compare the effect and safety of Shang Ring circumcision with those of conventional circumcision in the treatment of redundant prepuce or phimosis. METHODS: We retrieved the randomized controlled trials on Shang Ring circumcision and conventional circumcision for the treatment of redundant prepuce or phimosis published at home and abroad. Relevant data were selected according to the Cochrane Handbook for Systematic Reviews by two reviewers after quality evaluation of the included trials, and the statistical software RevMan 5.0 was used for meta analysis. RESULTS: Totally 8 randomized controlled trials with 2277 cases were included in this study. Compared with conventional circumcision, Shang Ring circumcision showed a shorter operation time (SMD = -5.82, 95% CI [ -7.39, 4.24], P<0.00001), less intraoperative blood loss (SMD = -3.28, 95% CI [ -3.47, 3.09], P<0.00001), lower rate of infection (OR = 0.44, 95% CI [0.26, 0.72], P=0.001), lower rate of postoperative bleeding (OR =0.05, 95% CI [0.02, 0.12], P<0.00001), higher rate of satisfaction with the postoperative penile appearance (OR=12.72, 95% CI [1.30, 124.56], P=0.03), lower intraoperative pain score (SMD = -3.32, 95% CI [ -3.50, -3.14], P<0.00001), and lower 24-hour-postoperative pain score (SMD = -3.28, 95% CI [ - 3.47, - 3.00], P<0.00001), but longer wound healing time (OR=1.46, 95% CI [1.03, 1.90], P<0.00001). CONCLUSION: In comparison with conventional circumcision, Shang Ring circumcision has the advantages of shorter operation time, fewer complications, mild pain, and higher rate of satisfaction with the postoperative penile appearance. However, more high-quality randomized controlled trials with large samples are required to lend further support to our findings. PMID- 24218952 TI - [Qilin pills combined with bromocriptine for idiopathic hyperprolactinemic oligoasthenozoospermia]. AB - OBJECTIVE: To observe the therapeutic effect of Qilin Pills combined with bromocriptine on idiopathic hyperprolactinemic (HPRL) oligoasthenospermia. METHODS: We conducted a randomized controlled study on 40 cases of idiopathic HPRL oligoasthenospermia, who were equally assigned to a trial group and a control group to be treated with Qilin Pills (6 g tid) combined with bromocriptine and bromocriptine alone, respectively, both for a course of 12 weeks. Then we observed the changes in the semen volume, sperm concentration, sperm motility and the levels of serum prolactin and testosterone, and compared the therapeutic results between the two groups before and after medication. RESULTS: Compared with the parameters before medication, both the trial and the control group showed significant improvement after treatment in sperm concentration ([11.60 +/- 3.90] x 10(6)/ml vs [28.10 +/- 13.50] x 10(6)/ml and [12.03 +/- 4.10] x 10(6)/ml vs [18.85 +/- 8.50] x 10(6)/ml), the percentage of grade a sperm ([8.75 +/- 6.65]% vs [24.35 +/- 13.25 ]% and [8.70 +/- 6.70] % vs [19.65 +/- 10.05]%), the percentage of grade a + b sperm ( [28.45 +/- 11.35]% vs [45.80 +/- 16.55]% and [27.65 +/- 10.65]% vs [35.66 +/-13.25]%), and sperm motility ([38.22 +/- 16.35]% vs [60.05 +/- 20.65]% and [37.25 +/- 15.75 ]% vs [52.65 +/- 18.25 ]%) (all P<0.01). No significant differences were found in semen volume (P>0.05). The serum prolactin levels were significantly decreased in the trial and control groups ([152.00 +/- 22.32] and [160.45 +/- 26.65] mIU/L), as compared with premedication ([482.25 +/- 65.32] and [477.32 +/- 60.25] mIU/L) (P<0.01), while the serum testosterone levels were remarkably higher ([16.35 +/- 5.52] and [11.15 +/- 4.65] nmol/L) than before treatment ([3.75 +/- 1.10] and [4.05 +/- 1.30] nmol/L) (P<0.01). There were no statistically significant differences in the serum prolactin and testosterone levels between the two groups after treatment (P>0.05). CONCLUSION: Qilin Pills combined with bromocriptine have a significantly better efficacy than bromocriptine alone in the treatment of idiopathic HPRL oligoasthenospermia. PMID- 24218953 TI - [Endothelial microparticles and erectile dysfunction: an update]. AB - Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury and/or apoptosis. Microparticles of various cellular origins, such as platelets, leukocytes, and endothelial cells, are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Recent studies show that endothelial microparticles, a kind of envelope particles derived from endothelial cells, not only constitute a marker of endothelial dysfunction, but also play a major biological role in the diagnostic and therapeutic approaches to erectile dysfunction. PMID- 24218954 TI - [Biological characteristics and application prospect of mesenchymal stem cells in male infertility]. AB - Mesenchymal stem cells (MSCs) are somatic stem cells capable of self-renewing and multipotent differentiation. They are also referred to as " seed cells" in tissue engineering. Recent years have witnessed great advances in the studies of the differentiative potential and paracrine function of MSCs, as well as in their clinical applications in several fields. As for their application in male infertility, researches are still in the stage of animal experiments. However, with deeper insights into their huge potential, novel and effective MSC-based therapies for male infertility will come into being in the near future. PMID- 24218955 TI - [Effect of continuous cropping of Rehmannia on its morphological and physiological characteristics]. AB - OBJECTIVE: In contrast to the newly-planted plants, through measuring and analyzing the chlorophyll content, photosynthetic characteristics, root activity and enzyme activity of Rehmannia glutinosa in growth stages, the differentiation manifestation of R. glutinosa physiological activity mediated by continuous cropping was studied. METHODS: SPAD-502 chlorophyll meter was used to measure chlorophyll content and LI-6400 portable photosynthetic apparatus to determine plant photosynthetic characteristics. Plant root vigor and enzyme system were measured following reference literature. RESULTS: The problems of Rehmannia caused by continuous cropping had happened since the early stage of its growth period, and lasted throughout the whole growth period. Under the condition of continuous cropping, the chlorophyll content, photosynthetic characteristics and root activity remained at a lower level compared with the newly-planted plants, among which, the chlorophyll content and the root activity (100 days after planting) had significant differences. CONCLUSION: The insufficient photosynthesis source and the reducing of the storage capacity (root tuber) under the condition of continuous cropping might be the main reasons for these problems of R. glutinosa. PMID- 24218956 TI - [Study on inducing embryogenic callus of Dioscorea zingiberensis by orthogonal design]. AB - OBJECTIVE: To select the suitable medium to induce embryogenic callus of Dioscorea zingiberensis. METHODS: Plantlet of Dioscorea zingiberesis in vitro was obtained by using apical meristem as explant. The different parts of the plantlets were cultured to select the best explant used for inducing callus and embryoids. Growing rate and diosgenin content were calculated in orthogonal test to optimize combination of phytohormones for inducing embryogenic callus. RESULTS: The leaves were suitable explants to induce callus and embryoid. The inducing rate of callus and embryoids reached 92.5% and 42.5%, respectively. The optimal medium for inducing embryogenic callus was MS + 6-BA 2.0 mg/L + NAA 0.5 mg/L + 2,4-D 1.0 mg/L. CONCLUSION: The results of this study can be used for effective induction of embryogenic callus of Dioscorea zingiberensis, and lay the foundation for the subsequent research of artificial seeds. PMID- 24218957 TI - [Anti-hepatic fibrosis effects research on serum containing extracts of Periplaneta americana in vitro]. AB - OBJECTIVE: To study the anti-hepatic fibrosis effect of serum containing extracts of Periplaneta americana. METHODS: The serum contained extracts of Periplaneta americana was prepared with serologic pharmacological method. MTT method was used to observe the effect of serum containing extracts from periplaneta americana on hepatic stellate cells (HSC), and Elisa method was used to detect the contents of TGF-beta1 and collagen I in supernatant. RESULTS: Serum containing extracts I and II (15%) of Periplaneta americana had inhibitory effect on HCS (P < 0.05) after HSC were cultured with serum containing extracts of different concentration of Periolaneta americana for 24, 48 and 72 h. At 24 and 48 h, serum containing extracts I and II of Periplaneta americana decreased the content of collagen I in supernatant without significant difference (P < 0.05). Serum containing extracts I (15%, 9%, 5.4%) of Periplaneta americana could reduce generation of TGF-beta1 in supernatant for 24 h (P < 0.05). As for 48 h, only high concentration serum containing extracts I (15%) deceased the content of TGF-beta1 in supernatant. For 24 and 48 h,serum containing extracts II couldn't reduce the content of TGF-beta1 in supernatant (P < 0.05). CONCLUSION: It has definite effect on anti-hepatic fibrosis with serum containing extracts of Periplaneta americana in vitro. The mechanism may be related to inhibiting HSC propagation and reducing the production of TGF-beta1. PMID- 24218958 TI - [Sequencing and analysis of the complete mitochondrial DNA of Chinese moccasin for medicinal use]. AB - OBJECTIVE: To sequence and analyze the complete mitochondrial DNA of Chinese moccasin. METHODS: The circular 17 541 bp sequence of mitochondrial DNA (mtDNA) of Chinese moccasin was determined by Ex-Taq PCR, TA-cloning and primer-walking methods. RESULTS: This mitogenome contained 37 coding genes (including 22 tRNA, 2 rRNA and 13 protein-coding genes) and two control regions (CR and psiCR). The gene content and arrangement of Chinese moccasin mtDNA was similar to those of other vipers reported so far. CONCLUSION: The characteristics of the replication origin and the tRNA arrangement of snake mitochondrial genomes can be used for identification of medicinal snakes. PMID- 24218959 TI - [Determination of trace elements in mylabris before and after being processed]. AB - OBJECTIVE: To discuss the processing principle of Mylabris by comparing the differences between the contents of 11 trace elements in Mylabris before and after being processed. METHODS: Used Flame AAS, Graphite Furnace AAS and Hydride generation AAS to determine the content of Cu, Mn, Zn, Fe, Mg, Ca, K, Pb, Cd, As and Hg elements in Mylabris samples. RESULTS: The sequence of 11 trace elements contents in the Mylabris samples from high to low was: K > Mg > Fe > Ca > Zn > Mn > Cu > Pb > As > Hg > Cd. In Mylabris after being processed, the contents of Pb, As, Hg, Cd and Fe elements decreased, Cu, Mg and Ca increased; In the head, legs and wings of Mylabris, the contents of Hg and Pb elements were higher than those of the other parts. The content of As in the inner wings was the highest. CONCLUSION: The traditional processing method, stir-frying with rice and removing head, legs and wings is scientific. PMID- 24218960 TI - [Development of full-quantified HPLC fingerprint for quality evaluation of ophiopogonis radix of sichuan]. AB - OBJECTIVE: To establish HPLC fingerprint of Ophiopogonis Radix of Sichuan and simultaneously determine two homoisoflavonoids (methylophiopogonanones A and B). METHODS: Full-quantified HPLC fingerprint was used to establish the HPLC fingerprint and determine the active ingredients of the daodi medicinal material Ophiopogonis Radix of Sichuan in Shengmai injection. Chromatographic condition was as follows: The analytical column was Waters symmetry shield RP 18 (4.6 mm x 250 mm, 5 microm) with a pre-column of symmetry shield RP 18. The mobile phase was acetonitrile-water (containing 0.1% phosphoric acid) with gradient elution. The flow rate was 1.0 mL/min, the detection wavelength was set at 280 nm and the column temperature was maintained at 30 degrees C. RESULTS: The HPLC fingerprint of Ophiopogonis Radix of Sichuan was established with good separation and repeatability. 24 common peaks were defined in the HPLC fingerprint. The similarity among batches was more than 0.98. Compared with standard reference substances, No. 14 peak was methylophiopogonanone A and No. 15 peak was methylophiopogonanone B. Similarity determine system was applied to evaluate them. CONCLUSION: This analytical method is highly sensitive with strong specificity, which can be used efficiently in the quality control of Ophiopogonis Radix of Sichuan in Shengmai injection. PMID- 24218961 TI - [UPLC fingerprint of rhei radix et rhizoma from different habitats]. AB - OBJECTIVE: To establish the UPLC fingerprint of Rhei Radix et Rhizoma and reference crude drugs, analyze the characteristics among fingerprints of three species of reference crude drugs and the common components of Rhei Radix et Rhizoma, and compare the application of different analysis methods. METHODS: UPLC procedure was performed on ACQUITY BEH C18 chromatographic column with mobile phase consisted of water (contained 0.1% phosphoric acid)-acetonitrile (gradient elution) at a flow rate of 0.21 mL/min. Detection wavelength was set at 260 nm and the column temperature was set at 30 degrees C. Fingerprints were analyzed by similarity evaluation, cluster analysis and principal component analysis. RESULTS: There were obvious characteristics among fingerprints of three species of reference crude drugs, 19 common chromatographic peaks were obtained from Rhei Radix et Rhizoma and 14 peaks were identified according to standard reference substances and by HPLC-MS. The cluster analysis and similarity evaluation showed the same result that 21 batches of sample were grouped into 5 categories and the result had no direct correlation with the botanical species. Both the contents of4 important ingredients suggested by principal component analysis and the whole fingerprint analysis were necessary in quality evaluation of Rhei Radix et Rhizoma. There was certain limitation in quality evaluation of multiple sources drug which analysis by similarity evaluation and cluster analysis. CONCLUSION: The method with good reproducibility and separation saves time and solvent, it can be used in identification of three species of reference crude drugs but can not be used in species identification of commercial Rhei Radix et Rhizoma. PMID- 24218962 TI - [Quality standard of zhuang medicine jasmini sambacis flos]. AB - OBJECTIVE: To study the qualitative and quantitative determination of Zhuang medicine Jasmini Sambacis Flos and establish its quality control standard. METHODS: Macroscopic, microscopic and TLC identification were adopted to carry out the qualitative identification, the mensuration of inspection items and extractum were according to the Chinese Pharmacopoeia. The contents of quercetin and kaempferide in Jasmini Sambacis Flos were determined by HPLC. RESULTS: The qualitative identification methods had strong specificity. In HPLC quantitative determination, the linear range of quercetin and kaempferide was in the range of 0.4008 - 3.2064 microg and 0.0403 - 3.2256 microg, respectively. CONCLUSION: These methods are simple, accurate and reproducible, and can be used to control the quality of Jasmini Sambacis Flos effectively. PMID- 24218963 TI - [Pharmacognostical study of Cyperus rotundus growing in Wen-River area]. AB - OBJECTIVE: To study the macroscopic, microscopic identification and chemical components of Cyperus rotundus growing in Wen-River area. METHODS: The features of different parts of Cyperus rotundus were described by material morphology and microscopic identification, the chemical components of aerial part and rhizome of Cyperus rotundus were studied by chemical experiment and GC-MS analysis. RESULTS: Summarized the transverse section structure of rhizome, stem and leaf of Cyperus rotundus, the chemical components of aerial part and the components and relative content of volatile oil in rhizome were determined. CONCLUSION: This study provides reference for the drug identification and the daodi medicinal material exploitation of Cyperus rotundus. PMID- 24218964 TI - [Chemical constituents from the aerial part of Echinacea purpurea]. AB - OBJECTIVE: To study the chemical constituents of the aerial part of Echinacea purpurea. METHODS: The compounds were separated and purified by repeatedly silica gel, ODS, D101 macroporous resin, MCI, Sephadex LH-20 column chromatography and recrystallization. Their structures were elucidated on the basis of physiochemical properties and spectral analysis. RESULTS: Sixteen compounds were isolated and identified as (2S)-1-O-octacosanoyl glycerol (1), (5R,6S)-6-hydroxy 6-((E)-3-hydroxybut-1-enyl)-1,1, 5-trimethylcyclohexanone (2), (3S, 6E, 10R)-3, 10, 11-trihydroxy-3, 7, 11-trimethyl-dodeca-1, 6-diene (3), negunfurol (4), schensianol A (5), ent-4 (15) -eudesmene-1beta, 6alpha-diol (6), (E) -5-hydroxy-N isobutylpentadec-2-enamide (7), syringaresinol (8), quercetin (9), ethyl laurate (10), ethyl caffeate (11), ferulic acid (12), alpha-spinasterol (13), stigmasterol (14), beta-daucosterol (15), octacosanoic acid (16). CONCLUSION: Compound 1 - 5 are isolated from the Asteraceae for the first time, compound 6 ,7, 9, 10, 12 are isolated from genus of Echinacea for the first time, compound 15, 16 are isolated from this plant for the first time. PMID- 24218965 TI - [Study on the chemical constituents from ethyl acetate extract of Micromelum falcatum]. AB - OBJECTIVE: To study the chemical constituents from ethyl acetate extract of Micromelum falcatum. METHODS: The constituents were separated and purified by silica gel, Sephadex LH-20 and HPLC. Their structures were elucidated by spectral analysis (NMR, MS). RESULTS: Ten compounds were isolated and identified as micropubescin (1), phebalosin (2), scopoletin (3), citrubuntin (4), thamnosmonin (5), hopeyhopin (6), arnottinin (7), casegravol (8), 2-methoxy-5-hydroxy cinnamate (9), threo-syringoylglycerol (10). CONCLUSION: Compounds 1 - 10 are obtained from this plant for the first time. PMID- 24218966 TI - [Study on chemical components of Aconitum flavum and their inflammatory and analgesic effects]. AB - OBJECTIVE: To study the chemical compositions of active site of Aconitum flavum and their pharmacological effects on anti-inflammatory andantalgic. METHODS: Xylene-induced mice ear swollen and egg white-induce toe swollen test were used to assess the anti-inflammatory effect of Aconitum flavum. Acetic acid-induce mice writhing and hot-plate test were used to assess the antalgic effect of Aconitum flavum. Silica gel, ODS and Sephadex LH-20 techniques were employed for isolation and purification the constituents of Aconitum flavum. The chemical compounds were identified by 1H-NMR, 13C-NMR, DEPT, HMBC, HMQC and COSY. RESULTS: When compared with model group, there was significant difference in 30% alcohol active extract group (P < 0.05) in xylene-induce mice ear-swollen test. In the experiment of egg white-induce toe swollen test, 30% alcohol active extract group had great significant difference when compared with the model group (P < 0.01). In acetic acid writhing test, 30% alcohol active extract group had significant analgesic action when compared with model group. In hot plate test, when compared with model group, the analgesic effect of 30% alcohol active extract group (P < 0.05) at 30 and 45 minutes after administration was significanty increased. Fourteen compounds were isolated from the active extract,while seven compounds were identified as: sucrose (I), linarin (Ii), beta-sitosterol (III), beta daucosterol (IV), beta-sitosterol-3, 5, 6-triol (VII), aconitine (V ) and hypaconitine (IV). CONCLUSION: 30% alcohol active extract of Aconitum flavum has anti-inflammatory and antalgic effects. Compounds I, II, IV, VI and VII are isolated for the first time. PMID- 24218967 TI - [Chemical constituents from flowers of Gardenia jasminoides]. AB - OBJECTIVE: To study the chemical constituents from flowers of Gardenia jasminoides. METHODS: The compounds were isolated and purified by column chromatography and their structures were elucidated through spectroscopic techniques (NMR) and physicochemical properties. RESULTS: 15 compounds were isolated from flowers of G. jasminoides, and identified as 5, 7, 3'-trihydroxy-6, 4', 5'-trimethoxyflavone (1), 5, 7, 3', 5'- tetrahydroxy-6, 4'-dymethoxyflavone (2), kaempferol (3), quercetin (4), 3beta,23- dihydroxyurs-12-en-28-oic acid (5), 3beta,19alpha-dihydroxy-urs-12-en-28-oic acid (6), 3beta,19alpha,23-trihydroxy urs-12-en-28-oic acid (7), emodin (8), physcion (9), crocin-I (10), beta daucosterol (11), beta-sitosterol (12), stearic acid (13), palmitic acid (14), oleic acid (15). CONCLUSION: Compounds 1 - 15 are isolated from flowers of G. jasminoides and compounds 5 and 6 are isolated from genus Gardenia for the first time. PMID- 24218968 TI - [Chemical composition of essential oil from Thymus citriodorus and its toxic effect on liver cancer cells]. AB - OBJECTIVE: To analyze the chemical composition of essential oil from Thymus citriodorus and its toxic effect on liver cancer cells. METHODS: The essential oil from Thymus citriodorus leaves was extracted by steam distillation, and GC-MS was used for analyzing chemical composition. 35 components were identified which accounted for 95.44% of the total peak area. The main components were borneol (28.82%), thymol (14.43%), 3, 7-dimethyl-1, 6-octadiene-3-ol (8.26%), 1-methyl-4 [alpha-hydroxy-isopropyl] cyclohexene (8.23%) and terpenes camphor (5.1%), et. al. The toxic effects on HepG2 cells and expression of NF-kappabeta65 were measured by MTT assay and confocal laser scanning microscopy, respectively. RESULTS: The IC50 of HepG2 cells inhibition was 0.34%. The mean fluorescence intensity of NF-kappabeta65 expression was as follows: control group 323.25, 2( 10) concentration group 84.18, 2(-11) concentration group 197.93 and 2(-12) concentration group 261.43. CONCLUSION: The essential oil from Thymus citriodorus leaves has strong toxic effects. The induced apoptosis mechanism may be associated with the expression of NF-kappabeta65. PMID- 24218969 TI - [Study on the diterpenoids of Tripterygium wilfordii by electrospray ionization tandem and electron impact mass spectrometry]. AB - OBJECTIVE: To study the diterpenoids of Tripterygium wilfordii by electrospray ionization tandem (ESI) and electron impact (EI) mass spectrometry and establish the methods for quickly and on line identification of these diterpenoids. METHODS: The diterpenoids were analyzed by ESI-MS and EI-MS under positive ion model. RESULTS: In ESI-Trap-MS (+) model, the quasi-molecular ions [M + H] + of the diterpenoids took place bond cleavage and generally lost neutral molecules such as H2O, CH2CHCH3, CO and CH2CO, then generated characteristic fragment ion series (m/z 197, 183, 169). In ESI-TOF-MS (+) model, the quasi-molecular ions [M + H] + of the diterpenoids took place bond cleavage and generally lost neutral molecules such as H2O, CO, then generated characteristic fragment ion series (m/z 277, 185, 93). In EI-MS model, the molecular ions of the diterpenoids took place bond cleavage and generally lost neutral molecules such as H2O, CO, CH4, and isopropyl radical, then generated characteristic fragment ion series (m/z 149, 105, 91, 71, 55, 43). CONCLUSION: The ESI-MS and EI-MS characteristics of diterpenoids of Tripterygium wilfordii are reported for the first time. Based on these characteristics, the methods for quickly and on line identification of diterpenoids are established. PMID- 24218970 TI - [Effect of meliae toosendan fructus on nerves system and its mechanism]. AB - OBJECTIVE: To study the effect of the ethanol extract of stir-bake to yellowish Meliae Toosendan Fructus on nerve system and its mechanism. METHODS: The effect of the ethanol extract on sensory nerve was carried out through ache models induced by hot board method and radiant heat stimulation method in mice. The thermalgesia liminal value was investigated. The effect of the ethanol extract on the A-delta fiber and C fiber was measured by electrical stimulation procedure. Motor nerve conduction velocity (NCV) was measured by indirect detection method in vivo. The pathology changes of the motor nerve were observed by transmission electron microscope and the silver stain test. RESULTS: The ethanol extract of Meliae Toosendan Fructus could increase the thermalgesia liminal value of mice and reduce the conduction velocity of motor nerves. Meanwhile, pathology results showed the changes of the fiber of motor nerve, including demyelination and the number of Schwann cells dropping. CONCLUSION: The ethanol extract of stir-bake to yellowish Meliae Toosendan Fructus can reduce the pain sensitivity of mice and slow down NCV, which may be related to decreasing of the number of Schwann cells. PMID- 24218971 TI - [Effect of flavonoids from hedysari radix on pulmonary functions of pulmonary fibrosis rat]. AB - OBJECTIVE: To study the effect of flavonoids from Hedysari Radix on pulmonary functions of pulmonary fibrosis rat and its mechanism. METHODS: 72 Wistar rats were randomly divided into 6 groups: blank control group, model group, prednisone group, Hedysari Radix flavonoids low, medium and high dosage group. The rat model was established by propelling bleomycin into bronchial tree through endotracheal intubation with laryngoscope. The pulmonary fanctions were measured. RESULTS: Hedysari Radix flavonoids could normalize the pulmonary functions of rats with bleomycin-induced pulmonary fibrosis. CONCLUSION: Hedysari Radix flavonoids can inhibit the process of pulmonary fibrosis. PMID- 24218972 TI - [Effect of shuganjianpifang on the expression of BCL-2 and BAX in rats livers with hepatic fibrosis]. AB - OBJECTIVE: To observe the effect of shuganjianpifang on BCL-2, BAX expressions in livers of hepatic fibrosis rats and its mechanism. METHODS: Sixty SD rats were randomly divided into six groups. Rat liver fibrosis was induced by CCl4 twice a week for 12 weeks. Shuganjianpifang was used daily via lavage at 7th week for 6 weeks. The contents of ALT, AST, T-BiL and Alb in serum were measured. Liver samples were taken to examine the degree of liver fibrosis by HE staining. The experessions of BCL-2 and BAX were detected by immunohisto chemistry. The expression of BCL-2, BAX mRNA was detected by RT-PCR technology. RESULTS: As compared with the fibrotic model group, shuganjianpifang significantly reduced histopathological change, such as steatosis, deposition, decreased the contents of ALT, AST and T-BiL, up-regulated the expression of Alb. Meanwhile shuganjianpifang could effectively inhibit the expression of BAX, significantly enhanced the expression BCL-2 in liver fibrosis rats. CONCLUSION: Shuganjianpifang can resist hepatic fibrosis possibly by up-regulating BCL-2 expression and down-regulating BAX expression. PMID- 24218973 TI - [Study on the regulation role of semen persicae to cAMP-PKA signal pathway in the rats with cold and heat blood stasis syndrome]. AB - OBJECTIVE: To study the regulation role of with neutral property to cAMP-PKA pathway in the rats with cold and heat blood stasis syndromes and it's mechanism. METHODS: 60 rats were randomly divided into normal control group, model control group, Semen Persicae group, radix salvia miltiorrhiza group, rhizoma chuanxiong group, 12 rats per group. The three herb groups were orally given relative herbs decoction, whose dosages were equal to 10 times the human clinical dose, normal and model control groups were orally given water, 2 times/day, 20 mL/kg, for 7 days. Experiments in rats with cold and heat blood stasis syndromes were carried on respectiverly. In heat blood stasis syndromes, except normal control group, the other groups were intraperitoneally injected 10% carrageenan, 5 mL/kg, 1 times/day, for 3 days;24 hours after the last injection, subcutaneously injected 20% dry yeast suspension, 10 mL/kg. In cold blood stasis syndromes, except normal control group, the other groups were put into fridge, temperature--(18 +/- 2) degrees C, 2 hours/ times, 2 times/day, for 7 days. Separately draw 5 ml abdominal aortic blood and taken abdominal aorta, 6 hours and 12 hours after finishing the model in the two syndromes. Tested the cAMP content by elisa, tested the PKA protein expression by Western blot. RESULTS: Semen Persicae with neutral property, could decrease the content of cAMP in plasma (P < 0.01), inhibit the expression of protein PKA (P < 0.05) in rats with heat stagnation and blood stasis syndrome, increase the plasma content of cAMP (P < 0.01) and increase the expression of protein PKA (P < 0.01) in rats with cold stagnation and blood stasis syndrome. Semen Persicae had two-way adjustment action on CAMP PKA signal pathway. CONCLUSION: In different internal environment of heat stagnation and blood stasis syndrome, cold stagnation and blood stasis syndrome, Semen Persicae with neutral property has two-way adjustment to cAMP-PKA signaling channel, which may be one of the mechanism of it's two-way application. PMID- 24218974 TI - [Comparative study on pharmacokinetics of gentiopicroside and gentianae radix extract in rats]. AB - OBJECTIVE: To compare the pharmacokinetics of gentiopicroside and Gentianae Radix extract in rats and assess the effect of other components in Gentianae Radix on the pharmacokinetics of gentiopicroside. METHODS: The rats were oral administrated with gentiopicroside and Gentianae Radix extract, the content of geritiopicroside was chosen as index and determined by HPLC. The pharmacokinetic parameters were calculated with DAS 2.1.1 program. RESULTS: The concentration time curve of gentiopicroside and Gentianae Radix extract was described by two compartment model. The main pharmacokinetic parameters of gentiopicroside and Gentianae Radix extract were: C(max) (16.53 +/- 0.37) g/mL and (16.61 +/- 0.49) g/mL, T(max) 0.25 h and 1.5 h, t1/2(alpha) (0.20 +/- 0.04) h and (0.69 +/- 0. 14) h, t /2 (beta) (0.64 +/- 0.08) hand (0.80 +/- 0.11) h, AUC(0-infinity) (18.20 +/- 1.97) g x h/mL and (39.20 +/- 1.18) g x h/mL, CL( 2.75 +/- 0.32) L/(h x kg) and (1.22 +/- 0.04) L (h x kg), respectively. CONCLUSION: There are significantly differences in pharmacokinetic parameters between gentiopicroside and Gentianae Radix extract in rats. PMID- 24218975 TI - [Solanum lyratum Thunberg alkaloid induces human lung adenoearcinoma A549 cells apoptosis by inhibiting NF-kappaB signaling pathway]. AB - OBJECTIVE: To investigate the effects of solanum lyratum Thunberg alkaloid (STA) on induction of apoptosis and the expression of NF-kappaB signaling pathway related genes in A549 cells. METHODS: A549 cells was treated with STA in vitro. The proliferation inhibitory effect was evaluated by MTT assay. Induction of cell apoptotic rate was determined by flow cytometry method (FCM) after Annexin V FITC/PI double staining. The expression of NF-kappaB/p65 in nuclei, Survivin, IkappaBalpha and p-1kaapaBalpha in cytosol were detected by western blot. RESULTS: STA exhibited strong proliferation inhibitory effect in a dose-and -time dependent manner against A549 cells. After treated with STA for 24 h, the apoptotic rate was increased significantly. The expression of IkappaBalpha protein was increased markedly,while those of NF-kappaB/p65, Survivin and p IkappaBalpha proteins were decreased markedly. CONCLUSION: STA can induce apoptosis of lung adenocarcinoma A549 cells, its mechanisms may be related to inhibition of NF-kappaB signaling pathway. PMID- 24218976 TI - [Study on extraction and purification technology of Hubei ophiopogon saponins]. AB - OBJECTIVE: To explore the extraction and purification technology of total saponins from the effective parts of Liriope spicata. METHODS: Orthogonal design was used. Macroporous resin was selected to separate and purify total saponin from the effective parts of Liriope spicata. The process validation was conducted. The total saponins was determined by Ultraviolet Spectrophotometry. RESULTS: The optimal extraction conditions were as follows: 10 times the amount of ethanol (70%) for each occasion and hot reflux (3 x 2 h). Total saponins was purified by D101 macroporous resin. The concentration of eluting ethanol was 50% 70%. Ethanol (70%) was selected as the best eluent. The result of process validation was consistent with the study. CONCLUSION: The process is simple and stable enough to significantly improve the extraction rate of the effective parts. The study can provide reference for the research and production of effective parts of traditional Chinese medicine such as Liriope spicata. PMID- 24218977 TI - [Extraction and purification of isocorydine from Dicranostigma leptopodum]. AB - OBJECTIVE: To optimize the conditions of extraction and purification of isocorydine from Dicranostigma leptopodum. METHODS: Extraction conditions of isocorydine were selected on the basis of orthogonal experimental design, the static adsorption/desorption experiments were used to evaluate the optimum resin. RESULTS: The optimum extraction parameters were as follows: the ratio of raw materials to solvent 1:15 (g/mL), extraction solvent 1% vitriol, the extraction three times and 1 h each time. LX28 resin exhibited higher adsorption efficiency. CONCLUSION: Under the above optimum conditions, the extraction yield of isocorydine is 0.88%. The purity of isocorydine can reach 85.34% with a yield rate of 68.64%. PMID- 24218978 TI - [Optimization for preparation technology of shangke jiefu lotion by orthogonal test]. AB - OBJECTIVE: To optimize the preparation technology of Shangke Jiefu lotion. METHODS: The extraction process was optimized by orthogonal test, with water addition, extraction times and time used for extraction as factors of investigation. In refined process test, alcohol precipitation concentration, time, and the relative density of extract were studied. Each factor had three levels. The content of sophorcarpidine and the yield of dry extract were used as the evaluation indexes. The content of sophorcarpidine was determined by HPLC, and dry extract rates were determined by drying method. RESULTS: The best extraction condition was as follows: the amount of water was 10 times of the medicinal materials, the decoction duration was 2 h and for 3 times. The optimum purification process was: alcohol precipitation concentration was 50%, time was 15 hours, relative density of extract was 1.05 g/mL. CONCLUSION: The optimized preparation technology of Shangke Jiefu lotion is stable, feasible and convenient. It provides a theoretical basis for standardized production. PMID- 24218979 TI - [Optimization of the extraction process of the effective components in fructus phyllanthi]. AB - OBJECTIVE: To optimize the extraction process of the effective components in Fructus Phyllanthi. METHODS: Using Fructus Phyllanthi from Puning, Guangdong as the raw materials, its extraction process was screened by the orthogonal design. The extraction rates of polyphenol from Fructus Phyllanthi under different extraction conditions were compared to determine the optimum extraction technology. The effects of the ratio of raw materials to liquid, extraction time, extraction temperature and extraction number on extraction rates of polysaccharose in Fructus Phyllanthi were also investigated. RESULTS: The optimum extraction conditions for polyphenol were as follows: 50% methanol as solvent, ratio of raw materials to liquid 1:10, extraction times 1, extraction time 90 min. The optimum extracting conditions for polysaccharose were as follows: ratio of raw materials to liquid 1:20, extraction time 3.0 h, extraction times 3, and extraction temperature 90 degrees C. CONCLUSION: The optimization of the extraction process for polyphenol and polysaccharide in Fructus Phyllanthi has a good reference guide for further developing a seris of health care products of Fructus Phyllanthi. PMID- 24218980 TI - [Discussion on the quality marker of rehmanniae radix praeparata in the Chinese Pharmacopoeia]. AB - OBJECTIVE: In the Chinese Pharmacopoeia (2010 edition), the minimum limit of verbascoside (acteoside) in Rehmanniae Radix Praeparata (RRP) was set at 0.20%, the rationality of the standard was evaluated in this paper. METHODS: 10 samples of Rehmanniae Radix (RR) and RRP were collected or prepared. According to the traditional method, different samples of RRP were prepared from the same batch of RR, and the content of verbascoside was determined by HPLC. RESULTS: The average content of verbascoside in RR and RRP was 0.0226% and 0.0097%, respectively, and their difference was up to the level of P < 0.01. The content of verbascoside was found decreased with processing time increasing. Long-time storage also results in substantial loss of verbascoside. CONCLUSION: Processing results in verbascoside decreasing significantly. It is unreasonable that RR and RRP have the same standard in the content of verbascoside. It is suggested that the maximum limit of verboscoside should be set in the new version of Chinese pharmacopoeia. PMID- 24218981 TI - Excellent electromagnetic absorption properties of poly(3,4 ethylenedioxythiophene)-reduced graphene oxide-Co3O4 composites prepared by a hydrothermal method. AB - The ternary composites of poly(3,4-ethylenedioxythiophene)-reduced graphene oxide Co3O4 (PEDOT-RGO-Co3O4) were synthesized and the electromagnetic absorption property of the composites was investigated. The structure of the composites was characterized with Fourier-transform infrared spectra, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscope. The electromagnetic parameters indicate the enhanced electromagnetic absorption property of the composites was attributed to the better impedance matching. On the basis of the above characterization, an electromagnetic complementary theory was proposed to explain the impedance matching. It can be found that the maximum reflection loss of PEDOT-RGO-Co3O4 can reach -51.1 dB at 10.7 GHz, and the bandwidth exceeding -10 dB is 3.1 GHz with absorber thickness of 2.0 mm. Therefore, the PEDOT-RGO-Co3O4 composites, with such excellent electromagnetic absorption properties and wide absorption bandwidth, can be used as a new kind of candidate for microwave absorbing materials. PMID- 24218982 TI - Viscosity-dependent Janus particle chain dynamics. AB - Iron oxide (Fe3O4) Janus particles assemble into staggered chains parallel to the field lines in an ac electric field. Subsequent application of an external magnetic field leads to contraction of the staggered chains into double chains. The relation between the viscosity of the surrounding solution and the contraction rate of the iron oxide Janus particle chains is studied. Further, the influence of particle size and chain length (i.e., number of particles in chain) on the contraction rate is investigated. The base material for the Janus structure is silica (SiO2) with particle sizes of 1, 2, and 4 MUm, and the cap material is Fe3O4. Addition of increasing amounts of glycerol to the aqueous system reveals that the contraction dynamics strongly correlate with the viscosity of the solution. The average chain contraction rate for each particle size can be fitted in the low viscosity range from 1 to 30 mPa.s with a power function of the form A/MU(0.9) - B/MU, in which the coefficients A and B are particle size, electric field, and magnetic-field-dependent constants. Using this function, the viscosity of an unknown solution can be determined, thereby pointing to the potential application of these Janus particle chain assemblies as in situ microviscometers. PMID- 24218983 TI - Extraction and analysis of silver and gold nanoparticles from biological tissues using single particle inductively coupled plasma mass spectrometry. AB - Expanded use of engineered nanoparticles (ENPs) in consumer products increases the potential for environmental release and unintended biological exposures. As a result, measurement techniques are needed to accurately quantify ENP size, mass, and particle number distributions in biological matrices. This work combines single particle inductively coupled plasma mass spectrometry (spICPMS) with tissue extraction to quantify and characterize metallic ENPs in environmentally relevant biological tissues for the first time. ENPs were extracted from tissues via alkaline digestion using tetramethylammonium hydroxide (TMAH). Method development was performed using ground beef and was verified in Daphnia magna and Lumbriculus variegatus . ENPs investigated include 100 and 60 nm Au and Ag stabilized by polyvynylpyrrolidone (PVP). Mass- and number-based recovery of spiked Au and Ag ENPs was high (83-121%) from all tissues tested. Additional experiments suggested ENP mixtures (60 and 100 nm Ag ENPs) could be extracted and quantitatively analyzed. Biological exposures were also conducted to verify the applicability of the method for aquatic organisms. Size distributions and particle number concentrations were determined for ENPs extracted from D. magna exposed to 98 MUg/L 100 nm Au and 4.8 MUg/L 100 nm Ag ENPs. The D. magna nanoparticulate body burden for Au ENP uptake was 613 +/- 230 MUg/kgww, while the measured nanoparticulate body burden for D. magna exposed to Ag ENPs was 59 +/- 52 MUg/kgww. Notably, the particle size distributions determined from D. magna tissues suggested minimal shifts in the size distributions of ENPs accumulated, as compared to the exposure media. PMID- 24218984 TI - Measurement and evaluation of the alar base in unilateral secondary lip nasal deformities by three-dimensional computed tomography. AB - Objective : This study aimed to analyze the asymmetry of the pyriform aperture and alar base in patients with unilateral secondary nasal deformities by three dimensional computed tomography (3D-CT). Methods : 3D-CT images of the subject group of 101 adult patients and of a control group of 65 normal adults were examined. Sixty-nine patients without alveolar bone grafting (ABG) were classified as Group A, and 32 patients with ABG were classified as Group B. Seven landmarks (INM, LPA, IPA, Gbase, Gsup, Glat, and Sbal) were measured for both the subject and control groups, and comparative analyses were done to assess the degree of asymmetry in the subject group. Results : For over 95% of Group A and 80% to 85% of Group B, the index of LPA and IPA showed asymmetry or marked asymmetry. The index of Gbase, Glat, Gsup, and Sbal showed symmetry for around 50% of Group A and about 60% of Group B. In Group A, dorsal, lateral, and caudal translocation was found on the cleft side in LPA and IPA, while all soft landmarks showed dorsal translocation. In Group B, caudal translocation was found in both LPA and IPA, but only LPA appeared dorsal on the cleft side, while Glat showed dorsal and caudal translocation. Conclusion : The results indicated that the degree of asymmetry of hard tissue landmarks far exceeded that of the soft tissue landmarks, and the degree of asymmetry of pyriform aperture was higher than expected for patients after ABG. PMID- 24218985 TI - Early mother-child interaction and later quality of attachment in infants with an orofacial cleft compared to infants without cleft. AB - Objective : The main objective of this study was to assess mother-child patterns of interaction in relation to later quality of attachment in a group of children with an orofacial cleft compared with children without cleft. Design : Families were contacted when the child was 2 months old for a direct assessment of mother child interaction and then at 12 months for a direct assessment of the child's attachment. Data concerning socioeconomical information and posttraumatic stress symptoms in mothers were collected at the first appointment. Participants : Forty families of children with a cleft and 45 families of children without cleft were included in the study. Families were recruited at birth in the University Hospital of Lausanne. Results : Results showed that children with a cleft were more difficult and less cooperative during interaction at 2 months of age with their mother compared with children without a cleft. No significant differences were found in mothers or in dyadic interactive styles. Concerning the child's attachment at 12 months old, no differences were found in attachment security. However, secure children with a cleft were significantly more avoidant with their mother during the reunion episodes than secure children without cleft. Conclusion : Despite the facial disfigurement and the stress engendered by treatment during the first months of the infant's life, children with cleft and their mothers are doing as well as families without cleft with regard to the mothers' mental health, mother-child relationships, and later quality of attachment. A potential contribution for this absence of difference may be the pluridisciplinary support that families of children with cleft benefit from in Lausanne. PMID- 24218986 TI - Multiresidue detection of fluoroquinolones: specificity engineering of a recombinant antibody with oligonucleotide-directed mutagenesis. AB - Screening of a group of antibiotics from foodstuffs has traditionally relied on sophisticated chemical or physical analysis methods, such as liquid chromatography and mass spectrometric applications. The equipment for these techniques is expensive and not always applicable for high throughput screening. There is a need for an easy and cost efficient detection method for simultaneous screening of structurally similar compounds. Here we describe the engineering of a recombinant antibody which was subjected to oligonucleotide targeted random mutagenesis to emphasize the generic specificity of fluoroquinolone binding. Phage display together with small sized fluoroquinolone derivatives was used to find antibodies of high affinity and generic specificity. The most improved antibody was used to develop a time-resolved fluorescence immunoassay which was further optimized and applied for the detection of fluoroquinolone residues from spiked whole milk samples. The assay can be used to efficiently screen all European Agency for the Evaluation of Medicinal Products (EMEA) controlled fluoroquinolones from whole milk samples with detection levels ranging from 0.2 to 68 MUg L(-1). PMID- 24218987 TI - Theoretical study of nascent solvation in Ni+ (benzene)m, m = 3 and 4, clusters. AB - The ligand versus solvent behavior of Ni(+)(C6H6)3,4 complexes was studied using density functional theory all-electron calculations. Dispersion corrections were included with the BPW91-D2 method using the 6-311++G(2d,2p) basis set. The ground state (GS) for Ni(+)(C6H6)3 has three benzene rings 3d-pi bonded to the metal. A two-layer isomer with two moieties coordinated eta(3)-eta(2) with Ni(+), and the other one adsorbed by van der Waals interactions to the Ni(+)(C6H6)2 subcluster, i.e., a 2 + 1 structure, is within about 8.4 kJ/mol of the GS. Structures with 3 + 1 and 2 + 2 ligand coordination were found for Ni(+)(C6H6)4. The binding energies (D0) of 28.9 and 26.0 kJ/mol for the external moieties of Ni(+)(C6H6)3,4 are much smaller than that for Ni(+)(C6H6)2, 193.0 kJ/mol, obtained also with BPW91-D2. This last D0 overestimates somehow the experimental value, of 146.7 +/- 11.6 kJ/mol, for Ni(+)(C6H6)2. The abrupt fall for D0(Ni(+)(C6H6)3,4) shows that such molecules are bound externally as solvent species. These results agree with the D0(Ni(+)(C6H6)3) < 37.1 kJ/mol limit found experimentally for this kind of two-layer clusters. The ionization energies also decrease for m = 2, 3, and 4 (580.8, 573.1, and 558.6 kJ/mol). For Ni(+)(C6H6)3,4, each solvent moiety bridges the benzenes of Ni(+)(C6H6)2; their position and that of one internal ring mimics the tilted T-shape geometry of the benzene dimer (Bz2). The distances from the center of the external to the center of the internal rings for m = 3 (4.686 A) and m = 4 (4.523 A) are shorter than that for Bz2 (4.850 A). This and charge transfer effects promote the (C(delta-)-H(delta+))(int) dipole-pi(ext) interactions in Ni(+)(C6H6)3,4; pi-pi interactions also occur. The predicted IR spectra, having multiplet structure in the C-H region, provide insight into the experimental spectra of these ions. PMID- 24218988 TI - Cutaneous metastases as an initial manifestation of visceral well-differentiated neuroendocrine tumor: a report of four cases and a review of literature. AB - Well-differentiated neuroendocrine tumors metastasize to the skin uncommonly, and only 35 cases are reported in the literature. In only five of these patients, cutaneous metastases were the presenting symptom of malignancy; herein, we report four such cases. Two patients were female and two male, aged 50-74 years (mean: 64.5 years), each with a solitary painless, slowly enlarging, non-ulcerated cutaneous nodule of 3-12 months duration (mean: 9 months). The lesions were on the scalp (n = 3) and trunk (n = 1), and ranged in greatest dimension from 0.5 to 2.5 cm. The distinction from other microscopically similar entities, and the interpretation of origination from gastrointestinal, pancreatic or respiratory system primaries, was made clinically, or was based on the morphological features and the immunohistochemical profile. One patient died of the disease progression after 36 months whereas two patients are alive with significant disease progression after 24 and 60 months. Metastatic neuroendocrine tumor should be considered in the differential diagnosis of cutaneous tumors with neuroendocrine morphology even in patients with no known history of visceral malignancy. PMID- 24218989 TI - Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu. AB - The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co solvent- and cyclodextrin-based approaches. Different combinations of co solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-beta-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague-Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar. PMID- 24218990 TI - Investigational drugs targeting cardiac fibrosis. AB - Fibrosis is an accumulation of proteins including collagen in the extracellular space, which has previously been considered as irreversible damage in various cardiovascular diseases including heart failure and hypertension. The pathophysiology of fibrosis is currently better understood and can be evaluated by non-invasive methods. Here, the authors present briefly the impact and molecular mechanisms of fibrosis in the myocardium and the promising therapeutic candidates including anti-hypertensive therapies, heart-rate lowering drugs, anti inflammatory agents, as well as other innovative approaches such as inhibitors of growth factors, miRNA or cell therapy. Surrogate end points allow for larger clinical trials than previously possible with endomyocardial biopsies, and magnetic resonance and molecular imaging should open new fields of research on cardiac fibrosis. Several pre-clinical findings are very promising, and some clinical data support the proofs of concept, mainly those with inhibitors of the renin-angiotensin system. These approaches open the field for regression of fibrosis and include the following: first, some of these drugs are widely used like renin-angiotensin system inhibitors; second, inflammation modulators; third, in near future entirely new approaches targeting the TGF-beta pathways, or others like cell therapies or genetic interventions. PMID- 24218992 TI - An integrative review of nurse-led community-based case management effectiveness. AB - BACKGROUND: Accountable, continuous and patient-centred care in community-based settings is increasingly needed to reduce fragmented care, especially to reduce patient readmission rates. Case management has been proven effective in reducing healthcare costs and in increasing continuity of care, but its effectiveness in community-based settings is not clear. AIM: The aim of this integrative review is to examine the effectiveness of community-based case management programmes in improving patient outcomes. METHODS: An integrative review of articles from PubMed, CINAHL and PsycInfo databases was undertaken to synthesize and analyse research about community-based case management and its outcomes. Studies looking for patient outcomes and empirical studies published since 2000 were included. A total 18 articles were retrieved from 2000 to 2013. RESULTS: Most of the included studies were conducted in the USA, but international studies with quantitative approaches were reviewed (n = 6). The review revealed that community-based case management significantly reduced hospital access outcomes, especially readmissions and increased cost effectiveness, patient clinical outcomes and patient satisfaction. LIMITATIONS: This study did not isolate studies of patients with diseases or demographic characteristics in common, resulting in large variations in disease and demographic factors. CONCLUSION: There is a base of evidence that community-based case management is effective. Because it provides quality, patient-centred care, case management should be used for major care coordination. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The benefits of community-based case management need to be announced to healthcare leaders and policymakers. PMID- 24218991 TI - Efficiency and safety of O6-methylguanine DNA methyltransferase (MGMT(P140K)) mediated in vivo selection in a humanized mouse model. AB - Efficient O6-methylguanine DNA methyltransferase (MGMT(P140K))-mediated myeloprotection and in vivo selection have been demonstrated in numerous animal models and most recently in a phase I clinical study in glioblastoma patients. However, this strategy may augment the genotoxic risk of integrating vectors because of chemotherapy-induced DNA damage and the proliferative stress exerted during the in vivo selection. Thus, to improve the safety of the procedure, we evaluated a self-inactivating lentiviral MGMT(P140K) vector for transduction of human cord blood-derived CD34+ cells followed by transplantation of the cells into NOD/LtSz-scid/Il2rgamma-/- mice. These experiments demonstrated significant and stable enrichment of MGMT(P140K) transgenic human cells in the murine peripheral blood and bone marrow. Clonal inventory analysis utilizing linear amplification-mediated polymerase chain reaction and high-throughput sequencing revealed a characteristic lentiviral integration profile. Among the bone marrow insertions retrieved, we observed considerable overlap to previous MGMT(P140K) preclinical models or the clinical study. However, no significant differences between our chemotherapy-treated and nontreated cohorts were observed. This also hold true when specific cancer gene databases and a functional annotation of hit genes by the Panther Database with respect to molecular function, biological process, or cellular component were assessed. Thus, in summary, our data demonstrate efficient and long-term in vivo selection without overt hematological abnormalities using the lentiviral MGMT(P140K) vector. Furthermore, the study introduces humanized mouse models as a novel tool for the pre-clinical assessment of human gene therapy related toxicity. PMID- 24218993 TI - Bupropion-SR for smoking reduction and cessation in alcohol-dependent outpatients: a naturalistic, open-label study. AB - BACKGROUND: We sought to determine whether sustained-release bupropion (bupropion SR) reduces smoking and promotes smoking cessation among alcohol-dependent (AD) smokers while they are in early recovery from alcohol. METHODS: We conducted an open-label, naturalistic study among AD smokers enrolled in an outpatient treatment program. The treatment group (n=58) was offered bupropion-SR and brief smoking cessation counseling. A control group (n=57) was matched to the treatment group by age, sex, ethnicity, cigarette use, and years of alcohol dependence. The controls received no smoking cessation intervention. We collected tobacco and alcohol abstinence data for 6 months after enrollment. RESULTS: Participants in the treatment group were more likely to abstain from smoking than controls, at any of the followup time points. The treatment group smoked less cigarettes per day (CPD) at baseline, 30 days and 180 days post-baseline, compared to controls. These findings persisted after adjusting for possible covariates. CONCLUSION: Bupropion-SR may be helpful to quit or reduce smoking for recently abstinent AD individuals. PMID- 24218994 TI - Critical review of the evidence on 5-aminosalicilate for chemoprevention of colorectal cancer in ulcerative colitis: a methodological question. AB - Even though the exact amount of the increased risk is not known, patients with Ulcerative Colitis (UC) are more likely to develop colonic malignancy compared with the general population. 5-aminosalicilic acid (5-ASA) compounds are the mainstay therapy for mild-moderate UC, and their use for chemoprevention of colorectal cancer has been proposed, but the evidences are not univocal. Aim of the present work is to critically revise the available data on 5- ASA utilization for cancer chemoprevention, as well as the possible impact in the management of UC patients. In clinical practice, in fact, the best means to measure the dimension of a therapeutic effect is the number needed to treat (NNT). In our study, we show how different basal risk of colorectal cancer reported in studies coming from Europe and USA can affect the NNT, making the strategy "cost effective" or not. Since prospective randomized controlled trials to address the chemopreventive effect of 5-ASA are not feasible, evidence relays upon observational studies that may imply several biases. Therefore, the heterogeneity of the data is mainly consequent to the different methodological approach of the published studies, in terms of study design, data collection, definitions of regular use of medication and measures of therapeutic efficacy. In addition, two meta-analyses are available with apparently conflicting results. Nonetheless, 5 ASA represents an ideal chemopreventive agent for its anti-inflammatory property, safety, acceptability and inexpensiveness, and even ECCO guidelines recommend 5 ASA long term use, as these compounds may decrease the incidence of CRC. PMID- 24218996 TI - Clinical relevance of the interaction when switching non-nucleoside reverse transcriptase inhibitors in patients infected with HIV. AB - Substitution of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with another drug of the same class combined with nucleoside reverse transcriptase inhibitors is a therapeutic strategy that can improve the tolerability of antiretroviral treatment. According to the pharmacokinetic properties of NNRTIs, this substitution generates pharmacokinetic drug interactions between NNRTIs, which could decrease NNRTI exposure and virological efficacy during the introductory phase of the new NNRTI. Pharmacokinetics and clinical data are reviewed to estimate the risk for switching from efavirenz to nevirapine, efavirenz to etravirine, efavirenz to rilpivirine and nevirapine to rilpivirine. PMID- 24218995 TI - Bridging differences in outcomes of pharmacoepidemiological studies: design and first results of the PROTECT project. AB - BACKGROUND: Observational pharmacoepidemiological (PE) studies on drug safety have produced discrepant results that may be due to differences in design, conduct and analysis. PURPOSE: The pharmacoepidemiology work-package (WP2) of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) project aims at developing, testing and disseminating methodological standards for design, conduct and analysis of pharmacoepidemiological studies applicable to different safety issues using different databases across European countries. This article describes the selection of the safety issues and the description of the databases to be systematically studied. METHODS: Based on two consensus meetings and a literature search, we selected five drug-adverse event (AE) pairs to be evaluated in different databases. This selection was done according to pre-defined criteria such as regulatory and public health impact, and the potential to investigate a broad range of methodological issues. RESULTS: The selected drug-AE pairs are: 1) inhaled long-acting beta-2 agonists and acute myocardial infarction; 2) antimicrobials and acute liver injury; 3) antidepressants and/or benzodiazepines and hip fracture; 4) anticonvulsants and suicide/suicide attempts; and 5) calcium channel blockers and malignancies. Six European databases, that will be used to evaluate the drug-AE pairs retrospectively, are also described. CONCLUSION: The selected drug-AE pairs will be evaluated in PE studies using common protocols. Based on consistencies and discrepancies of these studies, a framework for guiding methodological choices will be developed. This will increase the usefulness and reliability of PE studies for benefit-risk assessment and decision making. PMID- 24218997 TI - Ginger for prevention or treatment of drug-induced nausea and vomiting. AB - PURPOSE: In this review, potential benefits of oral ginger for prevention or management of drug- induced nausea and vomiting were evaluated based on the available evidences. METHOD: By searching medical resources including Scopus, PubMed, Medline, Cochrane central register of controlled trials and Cochrane database systematic reviews, available evidences were collected. Ginger, zingiber, nausea and vomiting were considered as keywords. RESULTS AND CONCLUSION: Various studies have evaluated effects of ginger in prevention and management of nausea and vomiting in different conditions such as pregnancy, chemotherapy, and post-operation. Evidences regarding anti-emetic effect of ginger in prevention and treatment of chemotherapy induced nausea and vomiting are limited and results are conflicting. More randomized clinical trials should be conducted to confirm efficacy of ginger in this regards. Ginger showed promising and attractive effects in preventing post-operative nausea and vomiting at least as add-on therapy. The exact role of ginger as anti-emetic in prevention of post- operative nausea and vomiting can be elucidated by future randomized clinical trials. PMID- 24218998 TI - Sources of information used when prescribing for children, a survey of hospital based pediatricians. AB - BACKGROUND: Due to the lack of properly tested medicines for children, there is little available information with regards to indications and dosing of medications in children. AIM: To collect data on sources where hospital based pediatricians obtain prescribing information when treating children and the extent of collaboration with the hospital pharmacist. METHOD: Two hundred and fifty pediatricians in different hospitals within different cities in Jordan were asked to fill in a structured questionnaire regarding information sources used when prescribing for children. RESULTS: Questionnaires were collected from 162 (64.8%) hospital based pediatricians, who have completed the questionnaire by the designated date. Most (75.5%) reported that the Lexi Comp's Drug Information Handbook was the source that they most frequently used for drug information when prescribing for in children. The BNF and the BNFc (British National Formulary for children) were found to be the most sources that contain sufficient information that aids pediatricians when prescribing for children. A minority (22%) claimed to consult with the hospital pharmacist when they face difficulties when prescribing for children. CONCLUSIONS: Pediatricians rely on different information sources when they prescribe for children. Those sources vary in their reliability in aiding pediatrician when prescribing. Further work should be done in the provision of useful information on pediatric drug therapy to pediatricians. More steps should be taking place to activate collaboration and interaction between pediatricians and pharmacists as well. PMID- 24218999 TI - Pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor. AB - Anticoagulants have a key role in the management of venous and arterial thromboembolic disorders. Traditional anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are effective but have limitations that make the management of thromboembolic disorders difficult. There is a clear need for new anticoagulants that are at least as effective as traditional agents but without their drawbacks. This review discusses the mechanism of action, pharmacokinetics, and pharmacodynamics of one of these newer agents - the direct Factor Xa inhibitor rivaroxaban - and provides an overview of the results of phase III clinical studies. Based on these results, rivaroxaban has gained approval for the prevention and treatment of several thromboembolic disorders in adult patients. Rivaroxaban, which has a rapid onset of action, targets free and clot-bound Factor Xa and Factor Xa in the prothrombinase complex. It reaches maximal plasma concentration 2-4 hours after administration and has a high bioavailability (80-100%). Rivaroxaban has several advantages over traditional anticoagulants. It does not require dose adjustment for age, sex, body weight, or ethnicity, and there is no requirement for routine coagulation monitoring because it has been shown to have predictable pharmacokinetics and pharmacodynamics. Furthermore, rivaroxaban has minimal food and drug interactions. The introduction of newer oral anticoagulants, such as rivaroxaban, that are convenient to administer and have predictable pharmacokinetic and pharmacodynamic profiles, could ultimately simplify patient management in clinical practice and may improve clinical outcomes across a broad range of thromboembolic disorders. PMID- 24219000 TI - K-Ras, intestinal homeostasis and colon cancer. AB - Activating Ras mutations, present in about 20% of human cancers, compromise the GTPase activity of Ras and therefore trigger accumulation of Ras in the GTP-bound state. Among the three family members, K-Ras, H-Ras and N-Ras, K-Ras is the most frequently mutated gene, with 30-50% of colon cancer patients harboring activating K-Ras mutations. Oncogenic mutations of K-Ras have been found at codons 12, 13, 61 and 146. Activation of Ras triggers constitutive activation of signaling pathways, including the MAPK and AKT pathways, which allows tumor cells to proliferate in the absence of growth factors and increases their survival. In addition, activated Ras triggers inflammation and thus promotes tumor progression in a cell non-autonomous manner. The presence of K-Ras mutations not only has prognostic value, but it also predicts the responsiveness of colon cancer patients to inhibitors of EGFR signaling. PMID- 24219001 TI - Cardiotonic steroids in adaptation to dietary salt intake. AB - For many years the concept relating salt to blood pressure (BP) changes has been debated and the concept of natriuretic hormone eliminating excessive sodium by direct inhibition of Na/K-ATPase has raised controversy. However, a recently discovered Na/K-ATPase signaling function has been widely confirmed and provided a novel mechanism to explain the relationship between sodium and blood pressure. Recently, we have demonstrated that activation of this Na/KATPase signaling function regulates sodium reabsorption in renal proximal tubules (RPTs) to correct sodium retention related volume expansion and BP increase. This mechanism demonstrates that rather than contributing to development and maintenance of hypertension, a properly regulated RPT Na/K-ATPase signaling has a protective effect by stimulating renal sodium excretion. A clear understanding of molecular mechanisms whereby the Na/K-ATPase signaling axis counterbalance volume expansion would have major pathophysiological and therapeutic implications for volume expansion mediated hypertension. In this review, we will focus on the effect of the newly appreciated cardiotonic steroids (CTS)-Na/K-ATPase signaling on RPT mediated sodium handling by coordinated regulation of the Na/K-ATPase and sodium/proton exchanger isoform 3 (NHE3). PMID- 24219002 TI - Drug-induced impulse control disorders: a review. AB - The essential characteristic of impulse disorders is the failure to resist an impulse, drive or temptation to perform an act that is harmful to the person or to others. Clearly, impulse control disorders can occur without an induction of any drugs, and they may lead to very problematic situations that affect the adjustment of the patient and need to be treated immediately. However, the subject of the present review is impulsivity induced by a variety of drugs. In this context, the most frequently established agents are dopaminergic agonists that may affect the mesolimbic dopaminergic pathway, such as cocaine and methamphetamine. In Parkinson's disease, the triggering effect of levodopa on pounding has been known since the first description of the condition by Friedman. In this paper, we reviewed the role of a variety of psychopharmacological agents, including dopaminergic ones on the occurrence of impulse control disorders, by searching the PubMed database for relevant articles published in the period between 1980 and 2012 August in detail. PMID- 24219003 TI - CD26: a multi-purpose pharmacological target. AB - CD26 is a widely expressed transmembrane glycoprotein with peptidase activity in its extracellular domain and which regulates multiple biological processes. It acts mainly as catabolic enzyme for a number of circulating proteins involved in common pathological conditions such as diabetes and cardiovascular disease and may represent a target to modulate bioavailability of crucial substrates. The aim of the present review is to summarize data regarding CD26-based pharmacological interventions. Four main subtopics were identified:1) CD26 as the target of pharmacological inhibitors to increase bioavailability of glucagon-like petide-1 (GLP-1) and hence to enhance GLP-1 glucose-lowering activity in diabetic patients; 2) role of CD26 in the physiology and pathology of the cardiovascular system; 3) the adverse prognostic value of CD26 expression on cancer cells; 4) CD26 down-regulation on lymphocytes as a mechanism of TGF-beta immunomodulation. PMID- 24219004 TI - Utilization of optimal study design for maternal and fetal sheep propofol pharmacokinetics study: a preliminary study. AB - Multiple blood samples are generally required for measurement of pharmacokinetic (PK) parameters. D-optimal design is a popular and frequently used approach for determination of sampling time points in order to minimize the number of samples, while optimizing the estimation of PK parameters. Optimal design utilizing ADAPT (v5, BSR, University of Southern California, Los Angeles) developed a sparse sampling strategy to determine measurement of propofol in pregnant sheep. Propofal was administered as supplemental anesthetic agent to inhalation anesthesia to mimic anesthesia for open fetal surgery. In our preliminary study, propofol 3 mg/kg was given as a bolus to the ewe, followed by propofol infusion at rate 450 mcg/kg/min for 60 minutes, then decreased to 75 mcg/kg/min for 90 more minutes and then ceased. A three compartment model described the PK parameters with the fetus assumed as the third compartment. Initially, sampling times were chosen from thirteen time points as previously stated in the literature. Using priori propofol PK estimates, the final 9 sample time points were proposed in an optimal design with a change in infusion rate occurring between 65 and 75 minutes and sampling proposed at 5, 15, 25, 65, 75, 100, 110, 150, and 180 minutes. D-optimal design optimized the number and timing of samplings, which led to a reduction of cost and man power in the study protocol while preserving the ability to estimate propofol PK parameters in the maternal and fetal sheep model. Initial evaluation of samples collected from three sheep using the optimal design strategy confirmed the performance of the design in obtaining effective PK parameter estimates. PMID- 24219005 TI - Phase II and pharmacological study of oral docetaxel plus cyclosporin A in anthracycline pre-treated metastatic breast cancer. AB - INTRODUCTION: Previously, we demonstrated that oral docetaxel plus the P glycoprotein (Pgp; ABCB1) inhibitor cyclosporin A (CsA) is safe and results in adequate exposure to docetaxel. This phase II study evaluates the anti-tumor activity, safety and pharmacokinetics of oral docetaxel in combination with CsA in women with advanced breast cancer. MATERIALS AND METHODS: Patients with measurable advanced breast cancer were given one flat dose of 100 mg oral docetaxel, preceded by one single dose of 15 mg/kg CsA, weekly for 6 weeks in a cycle of 8 weeks. Pharmacokinetic monitoring of docetaxel and CsA was performed in week 1 and 9. RESULTS: Thirty-three patients with a median age of 50 years were recruited. Thirty patients were evaluable for toxicity and twenty-six for response. All had received prior anthracycline treatment. The treatment was generally well tolerated with manageable toxicity although many patients needed a dose reduction, most commonly because of fatigue and uncomplicated neutropenia. The median treatment duration was 16 weeks (range 6 - 32). The overall response rate in evaluable patients was 42% (95% CI: 23 - 63) and the median overall survival was 12.2 months (8.4 - 23.1). The interpatient variability in the area under the curve of 100 mg orally administered docetaxel was moderate, respectively 49 and 30% in week 1 and 9. CONCLUSION: Weekly oral docetaxel, combined with the booster drug CsA, is an active and safe treatment in anthracycline pre-treated patients with advanced breast cancer. PMID- 24219006 TI - Comprehensive approach to sarcopenia treatment. AB - Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and death. Primary sarcopenia is considered to be age-related when no other cause is evident, other than ageing itself. Secondary sarcopenia should be considered when one or more other causes are evident, such as activity-, disease-, or nutrition-related sarcopenia. In this narrative review that focused on human studies, we summarize the pharmaceutical therapies (testosterone, dehydroepiandrosterone, estrogen, growth hormone, ghrelin, vitamin D, angiotensin converting enzyme inhibitor, and eicosapentaenoic acid) and nonpharmaceutical therapies (resistance training, protein and amino acid supplementation, and non-smoking) for counteracting primary sarcopenia. Testosterone and growth hormone improve muscle mass and muscle strength, but have several side effects. Although there are some intriguing pharmaceutical therapies to combat sarcopenia, resistance training combined with supplements containing amino acids are the most effective for preventing and treating age-related muscle wasting and weakness. The etiology of sarcopenia in the elderly is multi factorial. Patients with disuse syndrome and deconditioning often complicate the diagnosis, of not only activity-related sarcopenia, but also age-, disease-, and nutrition-related sarcopenia. In these cases a comprehensive approach to sarcopenia treatment should include pharmaceutical therapies for age-related sarcopenia and comorbid chronic diseases, resistance training, early ambulation, nutrition management, protein and amino acid supplementation, and non-smoking. The effect of pharmaceutical therapies for sarcopenia can be enhanced by this comprehensive approach. Future research on pharmaceutical therapies for counteracting sarcopenia should consider non-pharmaceutical therapies and also the causes of sarcopenia. PMID- 24219007 TI - The interaction potential of retigabine (ezogabine) with other antiepileptic drugs. AB - BACKGROUND: Retigabine is an antiepileptic drug (AED) that reduces neuronal excitability by enhancing neuronal KCNQ (Kv7) potassium channel activity. METHODS: This manuscript provides an overview of the drug-drug interaction potential of retigabine with other AEDs, using data collated from both in vitro work and clinical studies, either previously published or from relevant information collated during the development of retigabine. RESULTS: Retigabine is not a substrate for the major CYP enzymes and at clinically relevant concentrations there is little or no potential for retigabine to inhibit or induce the CYP enzymes or to inhibit the major renal drug transporters. The addition of retigabine to a range of existing AEDs showed little or no effect on the AED trough concentrations apart from a 20% decrease in lamotrigine concentrations. Results from a small phase II study showed that co-administration of valproic acid and topiramate had no impact on the PK of retigabine whereas carbamazepine and phenytoin increased the clearance of retigabine by approximately 27% and 36%, respectively. Conversely, a population PK analysis of combined data from phase I, II and III studies showed that none of the coadministered AEDs affected retigabine clearance apart from lamotrigine which lowered retigabine clearance by 6.7%. CONCLUSION: Retigabine is not metabolized by CYP isozymes and does not induce or inhibit these isozymes at clinically relevant concentrations. Therefore, retigabine is associated with a low potential for PK interactions with other drugs via CYP450. Overall, there was little or no potential for retigabine to interact with other available AEDs. Although some PK interactions were observed with lamotrigine, these are unlikely to be clinically relevant. PMID- 24219008 TI - Dynamically regulated miRNA-mRNA networks revealed by exercise. AB - BACKGROUND: MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period. RESULTS: Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR 21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation. CONCLUSIONS: We have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation. PMID- 24219009 TI - Evaluation of enrofloxacin use in koalas (Phascolarctos cinereus) via population pharmacokinetics and Monte Carlo simulation. AB - Clinically normal koalas (n = 6) received a single dose of intravenous enrofloxacin (10 mg/kg). Serial plasma samples were collected over 24 h, and enrofloxacin concentrations were determined via high-performance liquid chromatography. Population pharmacokinetic modeling was performed in S-ADAPT. The probability of target attainment (PTA) was predicted via Monte Carlo simulations (MCS) using relevant target values (30-300) based on the unbound area under the curve over 24 h divided by the minimum inhibitory concentration (MIC) (fAUC0-24 /MIC), and published subcutaneous data were incorporated (Griffith et al., 2010). A two-compartment disposition model with allometrically scaled clearances (exponent: 0.75) and volumes of distribution (exponent: 1.0) adequately described the disposition of enrofloxacin. For 5.4 kg koalas (average weight), point estimates for total clearance (SE%) were 2.58 L/h (15%), central volume of distribution 0.249 L (14%), and peripheral volume 2.77 L (20%). MCS using a target fAUC0-24 /MIC of 40 predicted highest treatable MICs of 0.0625 mg/L for intravenous dosing and 0.0313 mg/L for subcutaneous dosing of 10 mg/kg enrofloxacin every 24 h. Thus, the frequently used dosage of 10 mg/kg enrofloxacin every 24 h subcutaneously may be appropriate against gram-positive bacteria with MICs <= 0.03 mg/L (PTA > 90%), but appears inadequate against gram negative bacteria and Chlamydiae in koalas. PMID- 24219010 TI - Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta analysis of published studies. AB - BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is becoming an increasingly important health issue. However, there are no data on the change in prevalence of NAFLD within a population over time, especially in the mainland of China. The goal of this study was to estimate the pooled prevalence of NAFLD in the mainland of China. METHODS: Systematic literature searches were conducted in PubMed, Web of Knowledge, Chinese Web of Knowledge, Wangfang, Weipu, and SinoMed databases, as well as relevant articles published from 1997 to 2013, reporting prevalence estimates of NAFLD in the mainland of China. Summary estimates of prevalence were calculated with a random effects model. The effects of research methodology on the prevalence estimates were assessed using a meta-regression model. RESULTS: Forty-eight studies were identified with of a total of 356 367 subjects. The overall pooled prevalence of NAFLD was 20.09% (17.95-22.31%). Subgroup analyses showed the following results: male: 24.81% (21.88-27.87%), female: 13.16% (11.33-15.11%), for 18-30: 9.22% (6.93-11.81%), for 40: 16.77% (13.22-20.66%), for 50: 23.50% (19.57-27.66%), for 60: 26.89% (21.11-33.09%), for urban: 21.83% (18.00-25.92%), for rural: 20.43% (8.01-36.74%); study years in 2000-2006: 18.22% (14.32-22.48%), 20.00% (16.84-23.36%) for 2007-2009, and 18.93% (15.41-22.72%) for 2010-2013. CONCLUSIONS: The prevalence of NAFLD is lower than the estimates from developed countries. But it still reaches the epidemic proportions, and its prevalence is increasing. Meanwhile, a nationwide prevalence investigation should be conducted to confirm the estimates and determine more accurate rates for specific populations. PMID- 24219011 TI - Oxidation of survival factor MEF2D in neuronal death and Parkinson's disease. AB - AIMS: Dysfunction of myocyte enhancer factor 2D (MEF2D), a key survival protein and transcription factor, underlies the pathogenic loss of dopaminergic (DA) neurons in Parkinson's disease (PD). Both genetic factors and neurotoxins associated with PD impair MEF2D function in vitro and in animal models of PD. We investigated whether distinct stress conditions target MEF2D via converging mechanisms. RESULTS: We showed that exposure of a DA neuronal cell line to 6 hyroxydopamine (6-OHDA), which causes PD in animals models, led to direct oxidative modifications of MEF2D. Oxidized MEF2D bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity. Oxidative stress also increased the level of lysosomal associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate flux, and stimulated CMA activity. These changes resulted in accelerated degradation of MEF2D. Importantly, 6-OHDA induced MEF2D oxidation and increased LAMP2A in the substantia nigra pars compacta region of the mouse brain. Consistently, the levels of oxidized MEF2D were much higher in postmortem PD brains compared with the controls. Functionally, reducing the levels of either MEF2D or LAMP2A exacerbated 6-OHDA-induced death of the DA neuronal cell line. Expression of an MEF2D mutant that is resistant to oxidative modification protected cells from 6-OHDA-induced death. INNOVATION: This study showed that oxidization of survival protein MEF2D is one of the pathogenic mechanisms involved in oxidative stress-induced DA neuronal death. CONCLUSION: Oxidation of survival factor MEF2D inhibits its function, underlies oxidative stress-induced neurotoxicity, and may be a part of the PD pathogenic process. PMID- 24219012 TI - Cardiometabolic biomarkers in chronic plaque psoriasis before and after etanercept treatment. AB - OBJECTIVE: To assess cardiometabolic biomarkers in patients with psoriasis before and after etanercept treatment. METHODS: Patients with moderate-to-severe plaque psoriasis were randomized to etanercept 50 mg once or twice weekly, double blinded. Cardiometabolic biomarkers were assessed at baseline and after 12 weeks of treatment (n = 273). RESULTS: At baseline, 42% of patients had metabolic syndrome. Etanercept was not associated with any clinically relevant adverse effects on cardiometabolic biomarkers. In the once-weekly subgroup, significant mean percentage changes from baseline (p < 0.05) were observed for the quantitative insulin-sensitivity check index (QUICKI; -2.2%), apolipoprotein (Apo) A1 (3.2%), Apo B:Apo A1 ratio (-3.5%), leptin (8.6%) and high-sensitivity C reactive protein (hsCRP) (-65.5%); and in the twice-weekly subgroup for plasma insulin (15.9%), QUICKI (-2.7%), high-density lipoprotein cholesterol (HDL-C; 2.9%), apolipoprotein (Apo) A1 (2.8%), Apo B:Apo A1 (-4.6%) and hsCRP (-74.4%). CONCLUSION: Metabolic syndrome was common in these patients with moderate-to severe psoriasis. Etanercept treatment may provide some potentially favorable modulation of insulin sensitivity, HDL-C, Apo A1 and Apo B:Apo A1 ratio. PMID- 24219013 TI - Cross-hetero-dehydrogenative coupling reaction of phosphites: a catalytic metal free phosphorylation of amines and alcohols. AB - Phosphorylation of amines, alcohols, and sulfoximines are accomplished using molecular iodine as a catalyst and H2O2 as the sole oxidant under mild reaction conditions. This method provides an easy route for synthesizing a variety of phosphoramidates, phosphorus triesters and sulfoximine-derived phosphoramidates which are of biological importance. PMID- 24219014 TI - The accuracy of surrogate decision makers: informed consent in hypothetical acute stroke scenarios. AB - BACKGROUND: Over one third of stroke patients have cognitive or language deficits such that they require surrogate consent for acute stroke treatment or enrollment into acute stroke trials. Little is known about the agreement of stroke patients and surrogates in this time-sensitive decision-making process. We sought to determine patient and surrogate agreement in 4 hypothetical acute stroke scenarios. METHODS: We performed face to face interviews with ED patients at an academic teaching hospital from June to August 2011. Patients and the surrogates they designated were asked to make decisions regarding 4 hypothetical stroke scenarios: 2 were treatment decisions; 2 involved enrollment into a clinical trial. Percent agreement was calculated as measures of surrogate predictive ability. RESULTS: A total of 200 patient/surrogate pairs were interviewed. Overall patient/surrogate percent agreement was 76.5%. Agreement for clinical scenarios ranged from 87% to 96% but dropped to 49%-74% for research scenarios. CONCLUSIONS: Surrogates accurately predict patient preferences for standard acute stroke treatments. However, the accuracy decreases when predicting research participation suggesting that the degree of surrogate agreement is dependent on the type of decision being made. Further research is needed to more thoroughly characterize surrogate decision-making in acute stroke situations. PMID- 24219016 TI - Studying motivations to avoid pregnancy. PMID- 24219015 TI - Environmental factors selectively impact co-occurrence of problem/pathological gambling with specific drug-use disorders in male twins. AB - AIMS: Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence. DESIGN: Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence. SETTING: Computer-assisted telephone interviews in the community. PARTICIPANTS: Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry. MEASUREMENTS: Life-time DSM III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule. FINDINGS: All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA = 0.22; 95% confidence interval (CI) = 0.10-0.34] and non-shared environmental components (environmental correlation rE = 0.24; 95% CI = 0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA = 0.32; 95% CI = 0.05-1.0; rE = 0.36; 95% CI = 0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co occurrence with problem/pathological gambling (rA = 0.58; 95% CI = 0.45-0.73). CONCLUSIONS: Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders. PMID- 24219017 TI - Incorporating a service improvement project into an undergraduate nursing programme: a pilot study. AB - Although service improvement projects have been incorporated into some postregistration nurse education modules in the UK, they have not been generally available to pre-registration students. This paper reports on the implementation and evaluation of a pilot project in pre-registration nurse education at one university in eastern England. It concludes that the nursing students found the project to be a useful addition to their course. Supportive reactions were obtained from nurse managers, mentors and academics. A need to improve communication with clinical areas through the use of web-based materials was highlighted. PMID- 24219018 TI - Differential effects of head-mounted displays on visual performance. AB - Head-mounted displays (HMDs) virtually augment the visual world to aid visual task completion. Three types of HMDs were compared [look around (LA); optical see through with organic light emitting diodes and virtual retinal display] to determine whether LA, leaving the observer functionally monocular, is inferior. Response times and error rates were determined for a combined visual search and Go-NoGo task. The costs of switching between displays were assessed separately. Finally, HMD effects on basic visual functions were quantified. Effects of HMDs on visual search and Go-NoGo task were small, but for LA display-switching costs for the Go-NoGo-task the effects were pronounced. Basic visual functions were most affected for LA (reduced visual acuity and visual field sensitivity, inaccurate vergence movements and absent stereo-vision). LA involved comparatively high switching costs for the Go-NoGo task, which might indicate reduced processing of external control cues. Reduced basic visual functions are a likely cause of this effect. PMID- 24219019 TI - A case of cyclic esotropia with menstrual cycle. PMID- 24219020 TI - The preliminary study of individual cognitive behavior therapy for Japanese patients with social anxiety disorder. AB - Research has demonstrated the effectiveness of both individual and group cognitive behavior therapy (CBT) programs for social anxiety disorder (SAD) with patients in many countries. The present preliminary study reports the effectiveness of individual CBT for Japanese patients with SAD. Fifteen outpatients diagnosed with SAD completed an individual CBT program of six 50-min sessions with several components, including cognitive restructuring to modify cost and probability bias, repeated speech exposure, and homework about idiosyncratic anxiety-provoking situations. The results show that SAD symptoms improved after completion of the program. Large effect sizes were found for cognitive factors of SAD. In addition, repeated speech exposure was highly effective for improving the self-perception of subjective anxiety. The present findings suggest that an individual CBT program can be effective for reducing SAD symptoms with Japanese patients. PMID- 24219022 TI - Does evaluative pressure make you less or more distractible? Role of top-down attentional control over response selection. AB - People's ability to resist cognitive distraction is crucial in many situations. The present research examines individuals' resistance to attentional distraction under conditions of evaluative pressure. In a series of 4 studies, participants had to complete various attentional tasks while believing their intelligence was or was not under the scrutiny of an experimenter. Using a spatial cuing paradigm, Studies 1 through 3 demonstrated that feeling evaluated led participants to implement stronger feature-based attentional control, which resulted in more (or less) distraction when irrelevant information matched (did not match) the searched-for target. Study 4 ruled out the possibility that the above effects were due to voluntary shifts of attention and demonstrated that the control settings implemented under evaluative pressure resulted in stronger goal contingent response priming. Thus, the way individuals relate to the task-the performance context in which they are-induces strong attentional selection biases. Altogether, the present findings highlight an overlooked form of top-down modulation of attention based on performance self-relevance. Implications for both the current models of attentional control and the current hypotheses on the impact of evaluative pressure on cognition, as well as the consequences for more complex performances, are discussed. PMID- 24219023 TI - Transforming the mirror: power fundamentally changes facial responding to emotional expressions. AB - Major theories propose that spontaneous responding to others' actions involves mirroring, or direct matching. Responding to facial expressions is assumed to follow this matching principle: People smile to smiles and frown to frowns. We demonstrate here that social power fundamentally changes spontaneous facial mimicry of emotional expressions, thereby challenging the direct-matching principle. Participants induced into a high-power (HP), low-power (LP), or neutral state watched dynamic happy and angry expressions from HP and LP targets while we measured facial electromyography (fEMG) over the zygomaticus major ("smiling muscle") and corrugator supercilii ("frowning muscle"). For smiling, LP participants smiled to all targets, regardless of their expression. In contrast, HP participants exhibited standard smile mimicry toward LP targets but did not mimic the smiles of HP targets. Instead, HP participants smiled more when those HP targets expressed anger. For frowning, all participants showed a more intense mimicry pattern to HP targets. These results demonstrate that spontaneous facial responding-detected by sensitive, physiological measures of muscle activation dynamically adapts to contextual cues of social hierarchy. PMID- 24219021 TI - Correlates of cognitive change. AB - Although there has been considerable interest in identifying potential correlates of cognitive change, results of past studies have been inconsistent. The present study incorporated a number of methodological features intended to maximize sensitivity to detect characteristics of individuals with different amounts of cognitive change. Cognitive change in 5 cognitive abilities was analyzed with 2nd order latent growth curve models applied to data from a moderately large sample of healthy adults ranging from 18 to 99 years of age (Ns of 4,802 with 1 occasion, 2,265 with 2 occasions, and 1,128 with 3 occasions). There was significant individual difference variance in the longitudinal changes in several cognitive abilities, even in separate analyses of individuals between 18 years of age and 39, between 40 and 64, and 65 and over. Potential correlates of change included measures of self-rated health, vision, mood, personality, and lifestyle. Most of the potential correlates of change had high reliability, and several analyses were based on even more reliable factors determined by the variance common to multiple measures. Despite favorable conditions for detecting correlates of change, there was little evidence that cognitive change was moderated by any of the variables examined. Possible reasons for the inconsistent results regarding correlates of cognitive change are discussed. PMID- 24219024 TI - What drives the spatial agency bias? An Italian-Malagasy-Arabic comparison study. AB - In Western cultures, human interactions are generally envisaged such that the agent appears on the left, the recipient on the right, with action flowing from left to right. Here we explore the joint influence of 2 mechanisms driving such spatial asymmetries: the embodiment of script direction and the order in which subject and object are mentioned. A comparison of 3 language communities (Italian, Malagasy, Arabic) differing in script direction (left-right for Italian and Malagasy and right-left for Arabic) and in subject-object order (subject-verb object in Italian and Arabic and verb-object-subject in Malagasy) provides evidence for the assumption that both mechanisms contribute to the spatial asymmetry. PMID- 24219025 TI - Short-term intratumoral interleukin-12 expressed from an alphaviral vector is sufficient to induce an efficient antitumoral response against spontaneous hepatocellular carcinomas. AB - Interleukin-12 (IL-12) is an immunostimulatory cytokine that has shown strong antitumor effects in animal models of liver cancer. In order to overcome the severe toxicity associated with its systemic administration, we had previously tested different strategies based on IL-12 gene transfer to tumor cells or to the surrounding liver tissue. We obtained promising results both with a recombinant Semliki Forest virus (SFV) vector expressing high levels of IL-12 (SFV-IL-12) after intratumoral injection and with a plasmid vector [pTonL2(T)-mIL12] that allows liver-specific and inducible IL-12 expression. The aim of the present study was to compare the antitumor responses induced by both systems in a clinically relevant animal model of hepatocellular carcinoma (HCC) developed in L PK/c-myc transgenic mice. These animals overexpress the c-myc oncogene in their livers, giving rise to spontaneous hepatic tumors with latency, histopathology, and genetic characteristics similar to human HCCs. We observed that intratumoral inoculation of SFV-IL-12 induced growth arrest in most tumors, providing 100% survival rate, in contrast to no survival in control animals. Similar results were obtained with hydrodynamic injection of pTonL2(T)-mIL12 after long-term induction of IL-12 expression in the liver. However, tumor arrest was less evident in plasmid-treated mice and the survival rate was slightly lower, despite higher and more sustained levels of IL-12 and IFN-gamma in serum. The fact that SFV-IL-12 was able to induce both apoptosis and a type-I IFN response specifically in the tumor could explain why short-term IL-12 expression from this vector was sufficient to mediate an antitumoral response comparable with long term IL-12 expression driven by pTonL2(T)-mIL12. Since SFV-IL-12 could reduce the possible toxicity associated with long-term IL-12 expression, we believe that this vector could have a potential application for HCC gene therapy. PMID- 24219026 TI - Influence of bovine serum albumin and alginate on silver nanoparticle dissolution and toxicity to Nitrosomonas europaea. AB - Bovine serum albumin (BSA), a model protein, reduced the toxicity of 20 nm citrate silver nanoparticles (AgNP) toward Nitrosomonas europaea, a model ammonia oxidizing bacteria, through a dual-mode protection mechanism. BSA reduced AgNP toxicity by chelating the silver ions (Ag(+)) released from the AgNPs. BSA further reduced AgNP toxicity by binding to the AgNP surface thus preventing NH3 dependent dissolution from occurring. Due to BSA's affinity toward Ag(+) chemisorbed on the AgNP surface, increased concentrations of BSA lead to increased AgNP dissolution rates. This, however, did not increase AgNP toxicity as the dissolved Ag(+) were adsorbed onto the BSA molecules. Alginate, a model extracellular polysaccharide (EPS), lacks strong Ag(+) ligands and was unable to protect N. europaea from Ag(+) toxicity. However, at high concentrations, alginate reduced AgNP toxicity by binding to the AgNP surface and reducing AgNP dissolution rates. Unlike BSA, alginate only weakly interacted with the AgNP surface and was unable to completely prevent NH3-dependent AgNP dissolution from occurring. Based on these results, AgNP toxicity in high protein environments (e.g., wastewater) is expected to be muted while the EPS layers of wastewater biofilms may provide additional protection from AgNPs, but not from Ag(+) that have already been released. PMID- 24219027 TI - Interspecific scaling patterns of talar articular surfaces within primates and their closest living relatives. AB - The articular facets of interosseous joints must transmit forces while maintaining relatively low stresses. To prevent overloading, joints that transmit higher forces should therefore have larger facet areas. The relative contributions of body mass and muscle-induced forces to joint stress are unclear, but generate opposing hypotheses. If mass-induced forces dominate, facet area should scale with positive allometry to body mass. Alternatively, muscle-induced forces should cause facets to scale isometrically with body mass. Within primates, both scaling patterns have been reported for articular surfaces of the femoral and humeral heads, but more distal elements are less well studied. Additionally, examination of complex articular surfaces has largely been limited to linear measurements, so that 'true area' remains poorly assessed. To re-assess these scaling relationships, we examine the relationship between body size and articular surface areas of the talus. Area measurements were taken from microCT scan-generated surfaces of all talar facets from a comprehensive sample of extant euarchontan taxa (primates, treeshrews, and colugos). Log-transformed data were regressed on literature-derived log-body mass using reduced major axis and phylogenetic least squares regressions. We examine the scaling patterns of muscle mass and physiological cross-sectional area (PCSA) to body mass, as these relationships may complicate each model. Finally, we examine the scaling pattern of hindlimb muscle PCSA to talar articular surface area, a direct test of the effect of mass-induced forces on joint surfaces. Among most groups, there is an overall trend toward positive allometry for articular surfaces. The ectal (= posterior calcaneal) facet scales with positive allometry among all groups except 'sundatherians', strepsirrhines, galagids, and lorisids. The medial tibial facet scales isometrically among all groups except lemuroids. Scaling coefficients are not correlated with sample size, clade inclusivity or behavioral diversity of the sample. Muscle mass scales with slight positive allometry to body mass, and PCSA scales at isometry to body mass. PCSA generally scales with negative allometry to articular surface area, which indicates joint surfaces increase faster than muscles' ability to generate force. We suggest a synthetic model to explain the complex patterns observed for talar articular surface area scaling: whether 'muscles or mass' drive articular facet scaling is probably dependent on the body size range of the sample and the biological role of the facet. The relationship between 'muscle vs. mass' dominance is likely bone- and facet-specific, meaning that some facets should respond primarily to stresses induced by larger body mass, whereas others primarily reflect muscle forces. PMID- 24219028 TI - Measuring the nature and duration of symptoms of cervical cancer in young women: developing an interview-based approach. AB - BACKGROUND: Some young women experience delays in diagnosis of cervical cancer, but little research about ways of studying these delays has been published. A major challenge is that gynaecological symptoms are common in young women, but cervical cancer is rare. This study describes the development and testing of a measure for studying delays in diagnosis in young women with cervical cancer. METHODS: Prospective development of an interview measure and testing of its ability to reliably and systematically collect relevant data in two large hospitals in London, UK using 27 women aged 18-40 diagnosed with cervical cancer in the previous two years. We developed a semi-structured interview schedule and data extraction form to systematically collect data on symptoms (including nature and duration) and risk factors for delayed diagnosis from young women with cervical cancer. We piloted the measure among young women with cervical cancer (audiorecording it with their permission), refining it iteratively. To complete the measure, we developed a database for managing the data and a manual for using the schedule. Two researchers extracted data from the recorded interviews to assess inter-rater reliability. RESULTS: The final interview schedule yielded quantitative data on the nature and duration of symptoms and risk factors for delayed diagnosis. Inter-rater reliability was high. In the pilot, 12 of the 27 women were diagnosed via symptomatic presentation. Median time from the symptom triggering presentation to presentation was one month (interquartile range 0-4 months). Median time from presentation to diagnosis was three months (interquartile range 1-8.5 months). CONCLUSIONS: We have developed a reliable tool for measuring the nature and duration of symptoms in young women with cervical cancer. Pilot data suggest that a substantial proportion of women experience delay between first presentation and diagnosis. PMID- 24219029 TI - A nomogram including baseline prognostic factors to estimate the activity of second-line therapy for advanced urothelial carcinoma. AB - OBJECTIVE: To study the impact of the prognostic factors liver metastasis (LM), anaemia (haemoglobin [Hb] <10 g/dL), Eastern Cooperative Oncology Group performance status (ECOG-PS) >=1 and time from previous chemotherapy (TFPC) on the activity of second-line therapy for advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Twelve phase II trials evaluating second-line chemotherapy and/or biological characteristics (n = 748) in patients with progressive disease were pooled. Progression-free survival (PFS) was defined as tumour progression or death from any cause. The PFS rate at 6 months (PFS6) was defined from the date of registration and calculated using the Kaplan-Meier method. Response rate (RR) was defined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.0. A nomogram predicting PFS6 was constructed using the rms software package in R (http://www.r-project.org). RESULTS: Data regarding progression, anaemia, LM, ECOG-PS and TFPC were available from 570 patients in nine phase II trials. The overall median PFS was 2.7 months, PFS6 was 22.2% (95% confidence interval 18.8 25.9) and the RR was 17.5% (95% CI: 14.5-20.9%). For every unit increase in risk group, the hazard of progression in 6 months increased by 41% and the odds of response decreased by 48%. A nomogram was constructed to predict PFS6 on an individual patient level. The model was internally validated and was shown to have acceptable calibration performance. CONCLUSIONS: The RR and PFS6 vary as a function of baseline prognostic factors in patients receiving second-line therapy for advanced UC. A nomogram incorporating prognostic factors facilitates the evaluation of outcomes across phase II trials enrolling heterogeneous populations and helps select suitable agents for phase III testing. PMID- 24219031 TI - Measurement error in time-series analysis: a simulation study comparing modelled and monitored data. AB - BACKGROUND: Assessing health effects from background exposure to air pollution is often hampered by the sparseness of pollution monitoring networks. However, regional atmospheric chemistry-transport models (CTMs) can provide pollution data with national coverage at fine geographical and temporal resolution. We used statistical simulation to compare the impact on epidemiological time-series analysis of additive measurement error in sparse monitor data as opposed to geographically and temporally complete model data. METHODS: Statistical simulations were based on a theoretical area of 4 regions each consisting of twenty-five 5 km * 5 km grid-squares. In the context of a 3-year Poisson regression time-series analysis of the association between mortality and a single pollutant, we compared the error impact of using daily grid-specific model data as opposed to daily regional average monitor data. We investigated how this comparison was affected if we changed the number of grids per region containing a monitor. To inform simulations, estimates (e.g. of pollutant means) were obtained from observed monitor data for 2003-2006 for national network sites across the UK and corresponding model data that were generated by the EMEP-WRF CTM. Average within-site correlations between observed monitor and model data were 0.73 and 0.76 for rural and urban daily maximum 8-hour ozone respectively, and 0.67 and 0.61 for rural and urban loge(daily 1-hour maximum NO2). RESULTS: When regional averages were based on 5 or 10 monitors per region, health effect estimates exhibited little bias. However, with only 1 monitor per region, the regression coefficient in our time-series analysis was attenuated by an estimated 6% for urban background ozone, 13% for rural ozone, 29% for urban background loge(NO2) and 38% for rural loge(NO2). For grid-specific model data the corresponding figures were 19%, 22%, 54% and 44% respectively, i.e. similar for rural loge(NO2) but more marked for urban loge(NO2). CONCLUSION: Even if correlations between model and monitor data appear reasonably strong, additive classical measurement error in model data may lead to appreciable bias in health effect estimates. As process-based air pollution models become more widely used in epidemiological time-series analysis, assessments of error impact that include statistical simulation may be useful. PMID- 24219030 TI - Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke. AB - Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension. PMID- 24219033 TI - Layer-by-layer assembly of graphene oxide nanosheets on polyamide membranes for durable reverse-osmosis applications. AB - Improving membrane durability associated with fouling and chlorine resistance remains one of the major challenges in desalination membrane technology. Here, we demonstrate that attractive features of graphene oxide (GO) nanosheets such as high hydrophilicity, chemical robustness, and ultrafast water permeation can be harnessed for a dual-action barrier coating layer that enhances resistance to both fouling and chlorine-induced degradation of polyamide (PA) thin-film composite (TFC) membranes while preserving their separation performance. GO multilayers were coated on the PA-TFC membrane surfaces via layer-by-layer (LbL) deposition of oppositely charged GO nanosheets. Consequently, it was shown that the conformal GO coating layer can increase the surface hydrophilicity and reduce the surface roughness, leading to the significantly improved antifouling performance against a protein foulant. It was also demonstrated that the chemically inert nature of GO nanosheets enables the GO coating layer to act as a chlorine barrier for the underlying PA membrane, resulting in a profound suppression of the membrane degradation in salt rejection upon chlorine exposure. PMID- 24219032 TI - miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma. AB - BACKGROUND AND AIM: MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells. METHODS: A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC). RESULTS: (i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10. CONCLUSION: Our findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment. PMID- 24219034 TI - A survey sampling approach for pesticide monitoring of community water systems using groundwater as a drinking water source. AB - The ability to infer human exposure to substances from drinking water using monitoring data helps determine and/or refine potential risks associated with drinking water consumption. We describe a survey sampling approach and its application to an atrazine groundwater monitoring study to adequately characterize upper exposure centiles and associated confidence intervals with predetermined precision. Study design and data analysis included sampling frame definition, sample stratification, sample size determination, allocation to strata, analysis weights, and weighted population estimates. Sampling frame encompassed 15 840 groundwater community water systems (CWS) in 21 states throughout the U. S. Median, and 95th percentile atrazine concentrations were 0.0022 and 0.024 ppb, respectively, for all CWS. Statistical estimates agreed with historical monitoring results, suggesting that the study design was adequate and robust. This methodology makes no assumptions regarding the occurrence distribution (e.g., lognormality); thus analyses based on the design-induced distribution provide the most robust basis for making inferences from the sample to target population. PMID- 24219035 TI - Mechanisms of action of methotrexate. AB - As one of the most utilized disease-modifying anti-rheumatic drugs, methotrexate (MTX) has revolutionized the treatment of rheumatoid arthritis as well as many other non-rheumatic chronic inflammatory diseases. Far from a simple anti- proliferative agent as was once thought, our understanding of how it exerts its anti-inflammatory effects has grown over the years. The mechanisms of action of MTX are reviewed here, and we look at how this knowledge helps to explain some of its most common side effects. PMID- 24219036 TI - Update on methotrexate as the anchor drug for rheumatoid arthritis. AB - Methotrexate has become the "anchor drug" for rheumatoid arthritis (RA), taken by many more patients than any other disease modifying anti-rheumatic drug (DMARD) or biological agent. Methotrexate has greater efficacy and effectiveness than any other non-biologic DMARD, and greater tolerability and safety than other DMARDs. The efficacy of methotrexate is comparable to biologic agents in parallel clinical trials of DMARD-naive patients. Adequate responses to methotrexate monotherapy or combinations with other non-biologic DMARDs are seen in about two- thirds of patients with RA in usual care. The most efficacious treatments for RA reported in the rheumatology literature are seen in strategy trials with methotrexate as the anchor drug, without any biologic agent. Interpretation of significantly lower radiographic progression between methotrexate and biologic agents in clinical trials is over- stated regarding clinic consequences. The admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary. Accurate information concerning methotrexate as the anchor drug for RA should lead to better understanding of optimal use and better to patient outcomes in usual clinical care. PMID- 24219037 TI - Efficacy and safety of methotrexate in combination with other non-biologic disease-modifying antirheumatic drugs (DMARDs) in treatment of rheumatoid arthritis. AB - Methotrexate (MTX) is well-established as the "anchor drug" for patients with rheumatoid arthritis (RA), to be used early and aggressively, with higher long term effectiveness, tolerability, and safety than any other disease-modifying antirheumatic drug (DMARD). However, about 20% to 40% of patients experience incomplete responses to MTX and require further therapy, with options including other non- biologic DMARDs, low dose glucocorticoids, and biologic agents. Non biologic DMARDs in combination with MTX may provide similar efficacy to a biologic agent in clinical trials, with fewer adverse events and lower costs. This re- view presents a summary of 21 clinical trials documenting the efficacy and safety of MTX in combination with other non-biologic DMARDs. PMID- 24219038 TI - The role of concomitant methotrexate in biologic therapy for rheumatoid arthritis. AB - From the first use of biologic therapy for the management of rheumatoid arthritis, methotrexate (MTX) has been commonly used as co-therapy. There are a number of mechanistic reasons why MTX may improve the efficacy of biologics, including reduced antigenicity as well as reduced clearance of the biologic agent. Clinical trial data for tumor necrosis factor inhibitors and for other biologic agents does suggest added efficacy when these agents are used in combination with MTX. One exception may be the interleukin-6 receptor antibody tocilizumab, for which there is some data to suggest that monotherapy may be as effective as combined therapy with MTX. Post-marketing registry data also supports the concomitant use of MTX with biologics, with evidence for greater efficacy and longer persistence on treatment when compared with monotherapy. PMID- 24219039 TI - Evidence that the strategy is more important than the agent to treat rheumatoid arthritis. Data from clinical trials of combinations of non-biologic DMARDs, with protocol-driven intensification of therapy for tight control or treat-to-target. AB - Eight major "strategy trials" in rheumatoid arthritis (RA) are reviewed, with protocol-driven escalation of combinations of methotrexate and other small molecule non-biological disease modifying antirheumatic drugs (DMARDs). All documented the value of intensive treatment adjusted according to quantitative data, generally a disease activity score (DAS) or its 28 joint count version (DAS28). Three of the 8 trials, TICORA, Dutch DAS-driven care, and CAMERA, may be termed "pure strategy trials," to com- pare a protocol-driven "intensive" strategy to usual care. Five other trials, BeSt, CIMESTRA, TICORA 2, Step-down versus step-up, and TEAR, may be termed "hybrid trials," in which an initial parallel design was supplemented with incremental protocol-driven intensification of treatment. A strategy of aiming for low disease activity or remission appears more important than the specific agent used. In group data, the proportion of good responses seen in these trials with combinations of non-biologic, small molecule DMARDs are comparable to data from clinical trials of biological agents although responses appear more rapid with biological agents, and certain individual patients may require a biologic agent for adequate control. These trials also illustrate the value of a quantitative index, monitored frequently for rational intensification of therapy. The data make a compelling case for both routine monitoring with a quantitative index and consideration of routine adjustment of therapy at each visit. Combinations of methotrexate with other non biologic DMARDs and glucocorticoids, toward a target of low disease activity or remission, may improve outcomes for patients with RA at levels similar to biologic agents in many patients. PMID- 24219040 TI - Methotrexate in psoriatic arthritis. AB - Psoriatic arthritis (PsA) is a form of inflammatory arthritis that occurs in patients with psoriasis and is distinct from rheumatoid arthritis (RA). Methotrexate (MTX) is one of the most commonly used drugs for the treatment of PsA, yet there is scant controlled trial data to document its efficacy. Controlled trials have not demonstrated significant separation from placebo, but the studies have significant limitations which inhibit our ability to draw firm conclusions about the efficacy of MTX. A number of observational studies have described benefit for joint and skin disease. As yet unstudied, are the effects on enthesitis, dactylitis, and spondylitis of PsA. Psoriasis studies have shown modest benefit for psoriatic skin lesions. It is not yet known if MTX contributes an additive or synergistic benefit when used in combination with TNF inhibitors in PsA. The potential value of low dose MTX to suppress antibody formation against biologic therapies should be considered in a patient fail- ing benefit from such therapy. Although adverse effects are similar to those seen in RA treatment with MTX, awareness of the tendency for PsA and psoriasis patients to be obese and have non-alcoholic steatohepatosis, which may amplify transaminitis potential, should be borne in mind. PMID- 24219041 TI - Parenteral methotrexate for the treatment of rheumatoid arthritis. AB - Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available. It has a well-established safety and efficacy profile and is the preferred first line agent for RA treatment. Historically, oral (PO) preparations of MTX have been used in the USA with minimal parenteral (subcutaneous, SC, and intramuscular, IM) administration. Several shortages of drug availability in a parenteral form have been possibly one of the reasons for this low level of use. Several studies have looked at the role of parenteral MTX in RA treatment, and these overall demonstrate better tolerability, bioavailability, and possible efficacy of MTX compared with PO preparation. PMID- 24219042 TI - Development and testing of a patient-centred care competency scale for hospital nurses. AB - This study aimed to develop and test the psychometric soundness of a patient centred care competency (PCC) scale for hospital nurses. A cross-sectional questionnaire survey was conducted among 594 nurses in two teaching hospitals (response rate 99.5%). Reliability and validity analyses were performed. The PCC scale consisted of 17 items divided into four subscales: respecting patients' perspectives (6 items), promoting patient involvement in care processes (5 items), providing for patient comfort (3 items) and advocating for patients (3 items). The Cronbach's alpha coefficient of the entire scale was 0.92, and those for the subscales were 0.85, 0.81, 0.84 and 0.80, respectively. Multitrait scaling analysis indicated that the four subscales had satisfactory convergent and discriminant validity. Significant correlations were found between total PCC scores and overall self-ratings of patient-centred care performance (r = 0.60, P < 0.001). The PCC scale was therefore determined to be a highly valid and reliable tool. PMID- 24219043 TI - Does perverse economic incentive lead to the irrational uses of medicines? PMID- 24219045 TI - The clinical and economic impact of bivalirudin for percutaneous coronary intervention. AB - Bivalirudin (BVR) is a direct thrombin inhibitor used as an adjunctive antithrombotic agent in combination with aspirin and an ADP-receptor blocker in patients with acute coronary syndrome undergoing percutaneous coronary intervention. When compared to a strategy of heparin plus a glycoprotein IIb/IIIa inhibitor, BVR has been shown in a number of randomized clinical trials to be at least as effective at reducing ischemic endpoints and to have a consistently lower rate of bleeding complications. In addition, various economic analyses have shown it to be cost-effective compared to heparin plus a glycoprotein IIb/IIIa inhibitor and this, coupled with its proven clinical efficacy, has led to the incorporation of BVR into both EU and US clinical guidelines. Previous studies with BVR have mostly assessed its use in patients treated with aspirin and clopidogrel and further studies are ongoing to determine its role in combination with newer, more potent oral antiplatelet agents. PMID- 24219046 TI - Using the probability-probability plot and index to augment interpretation of treatment effect for patient-reported outcome measures. AB - The interpretation of treatment effect can pose challenges, especially for patient-reported outcomes. As subjective assessments, patient-reported outcomes frequently lack a historical record to support what their scores mean, making their interpretation of treatment differences challenging. We show how the probability-probability (p-p) plot a graph of the test-treatment distribution percentiles versus the control-treatment distribution percentiles, can complement and supplement interpretation of treatment effect. From this plot, we introduce the p-p index as a new measure of treatment effect, illustrating the method with two examples. The p-p index represents, across all percentiles, the average difference in percentile rank for any pair of subjects on two different treatments with the same outcome score. This measure, which complements other metrics of treatment effect, captures full information by integrating across all percentiles and thus accurately summarizes and augments the interpretation of treatment effect. PMID- 24219047 TI - Cost-effectiveness analysis of rheumatic heart disease prevention strategies. AB - Rheumatic heart disease (RHD), secondary to group A streptococcal infection is endemic in the developing as well as parts of the developed world with significant costs to the patient, and to the healthcare system. We briefly review the prevalence and cost of RHD in developed and developing nations. We subsequently develop a Markov model to evaluate the cost-effectiveness of three strategies (vs standard no prevention) for preventing RHD in a developing world country: primary prophylaxis (throat swab to detect and subsequently treat group A streptococci as needed); primary prophylaxis (antibiotic prophylaxis for all) with benzathine penicillin G once monthly to all patients (ages 5-21 years) regardless of evidence of infection; and secondary prophylaxis with monthly only to those with echocardiographic evidence of early RHD. Our model suggests that echocardiographic screening and secondary prophylaxis is the best strategy although the strategies change depending on parameters used. PMID- 24219048 TI - Economic implications of potential drug-drug interactions in chronic pain patients. AB - Chronic pain patients may be subject to polypharmacy because of long-term pharmacological pain treatment and additional comorbidities. Many chronic pain patients expose themselves to potential drug-drug interactions (DDIs) and these interactions can have unintended and severe consequences. Prevalence and costs associated with DDIs are inconsistent and has led to an inadequate level of awareness among the medical community; therefore, it has become necessary to re evaluate the rates of DDIs in chronic pain patients. Utilizing medical and prescription claims databases, five studies were conducted to assess the health care utilization of and associated financial payments for patients >18 years with chronic noncancer pain. The studies evaluated drug-drug exposures with the potential to cause DDIs specifically occurring through the CYP450 enzyme system. The studies reported that drug-drug exposures are prevalent, costly and can occur in any age group and that physicians should consider ways to limit their patients' exposure to potential DDIs. PMID- 24219049 TI - Differential pricing of new pharmaceuticals in lower income European countries. AB - Pharmaceutical companies adjust the pricing strategy of innovative medicines to the imperatives of their major markets. The ability of payers to influence the ex factory price of new drugs depends on country population size and income per capita, among other factors. Differential pricing based on Ramsey principles is a 'second-best' solution to correct the imperfections of the global market for innovative pharmaceuticals, and it is also consistent with standard norms of equity. This analysis summarizes the boundaries of differential pharmaceutical pricing for policymakers, payers and other stakeholders in lower-income countries, with special focus on Central-Eastern Europe, and describes the feasibility and implications of potential solutions to ensure lower pharmaceutical prices as compared to higher-income countries. European stakeholders, especially in Central-Eastern Europe and at the EU level, should understand the implications of increased transparency of pricing and should develop solutions to prevent the limited accessibility of new medicines in lower income countries. PMID- 24219050 TI - Risk selection in a regulated health insurance market: a review of the concept, possibilities and effects. AB - The Dutch basic health insurance is based on the principles of regulated competition. This implies that insurers and providers compete on price and quality while the regulator sets certain rules to achieve public objectives such as solidarity. Two regulatory aspects of this scheme are that insurers are not allowed to risk rate their premiums and are compensated for predictable variation in individual medical expenses (i.e., risk equalization). Research, however, indicates that the current risk equalization is imperfect, which confronts insurers and consumers with incentives for risk selection. The goal of this paper is to review the concept, possibilities and potential effects of risk selection in the Dutch basic health insurance. We conclude that the possibilities for risk selection are numerous and a potential threat to solidarity, efficiency and quality of care. Regulators should be aware that measurement of risk selection is a methodological and data-demanding challenge. PMID- 24219051 TI - Mapping utilities from cancer-specific health-related quality of life instruments: a review of the literature. AB - Cancer-specific health-related quality of life instruments are often used to evaluate the patients' quality of life in clinical trials. However, these instruments cannot be used in economic evaluation to guide resource allocation decisions. Mapping is an approach that enables utilities to be predicted for use in cost-utility analysis. The purpose of this study was to review the literature on the mapping methods used to determine utilities from two cancer-specific instruments. Thirteen studies were identified and a total of 53 models were reported. Most of the studies employed an ordinary least squares method and did not conduct an out-of-sample validation. There is a need for more rigorous and robust mapping studies to be conducted to ensure appropriate funding recommendations are being made. PMID- 24219052 TI - Attention-deficit/hyperactivity disorder: an update on medication adherence and persistence in children, adolescents and adults. AB - Suboptimal adherence to treatment regimens is a major obstacle to treatment efficacy and positive outcomes for patients. While poor adherence is common across a variety of chronic conditions, an area which presents unique challenges to clinicians and researchers is non-adherence among pediatric populations. These challenges are well illustrated by the management of attention deficit/hyperactivity disorder (ADHD), a pervasive pediatric psychiatric condition. The average rates of non-adherence in children and adults ranged between 15 and 87%. Factors predicting increased adherence/persistence included the use of long-acting formulations, younger age, Caucasian background, family structure and the presence and treatment of comorbidities. Decreased adherence/persistence were predicted by multiple daily dosing, family history of ADHD, experiences of adverse effects, stigma and treatment inefficacy. The broad range of non-adherence rates identified reflects the complexities of adherence research in ADHD, and highlights the need for better standardization of adherence/persistence definitions and measurement approaches. PMID- 24219053 TI - HRQoL of European children and adolescents with short stature as assessed with generic (KIDSCREEN) and chronic-generic (DISABKIDS) instruments. AB - Short stature may be associated with impairments in health-related quality of life (HRQoL). This study compared the HRQoL of children/adolescents diagnosed with short stature to population norms and examined the effects of height deviation and treatment status on HRQoL. METHOD: We cross-sectionally assessed 110 children/adolescents aged 8-18, with current short stature (height deviation <=-2 standard-deviation (SD)) or normal height achieved since diagnosis, and 98 parents, using the generic KIDSCREEN and the chronic-generic DISABKIDS instruments. RESULTS: Generic HRQoL of patients was similar to population norms. Patients with achieved normal height reported better chronic-generic HRQoL when untreated, while patients with current short stature reported better HRQoL upon receiving treatment. Parents reported better HRQoL for treated patients, especially for girls. CONCLUSION: Although their HRQoL is not significantly compromised, patients diagnosed with short stature may profit from growth-hormone treatment. Specific instruments are needed to adequately assess the effectiveness of treatment. PMID- 24219054 TI - Influence of explanatory and confounding variables on HRQoL after controlling for measurement bias and response shift in measurement. AB - The purpose of this study was to examine the influence of explanatory and confounding variables on health-related quality of life after accounting for response shift, measurement bias and response shift in measurement using structural equation modeling. Hypertensive patients with coronary artery disease randomized to anti-hypertensive treatment, completed the ShortForm-36 questionnaire at both baseline and 1 year (n = 788). Three measurement biases were found and all three were considered as response shift in measurement. Older patients reported worse scores for both physical functioning (PF) and role physical at baseline and 1 year later compared to younger patients; and males reported better PF than females after conditioning on the latent trait of general physical health. Before controlling for response shift, patients' PF scores were not statistically different over time; however, PF scores significantly improved (p < 0.01) after controlling for recalibration response shift. Assessment of how patients perceive their change in health-related quality of life over time is warranted. PMID- 24219055 TI - Burden of smoking on quality of life in patients with chronic obstructive pulmonary disease. AB - The objective of this study was to assess the impact of smoking on health-related quality of life, Work Productivity and Activity Impairment (WPAI) in chronic obstructive pulmonary disease (COPD) patients. Respondents of the 2009/2010 US National Health and Wellness Survey (NHWS), aged >= 40 years, with COPD, chronic bronchitis or emphysema, were included in the study. Current and former (had not smoked for >= 11 years) smokers were compared. Physical component summary (PCS) and mental component summary (MCS) scores from the Short Form-12 version 2 (SF 12v2), health utilities (SF-6D) and WPAI were evaluated. Differences between current (n = 1685) and former (n = 1932) smokers were revealed: MCS (44.80, 46.73; p < 0.01); PCS (35.12, 35.79; p < 0.1); SF-6D (0.63, 0.65; p < 0.05). WPAI: presenteeism (23%, 18%; p < 0.05); work impairment (25%, 21%; p < 0.05); activity impairment (52%, 49%; p < 0.01). In conclusion, COPD patients who smoke have poorer health-related quality of life, impaired productivity and higher healthcare costs than former smokers. PMID- 24219056 TI - Self-assembly of squalene-based nucleolipids: relating the chemical structure of the bioconjugates to the architecture of the nanoparticles. AB - Squalene-based nucleolipids, including anticancer or antiviral prodrugs, gave rise to nanoparticles displaying a diversity of structures upon nanoprecipitation in water. Synchrotron small-angle X-ray scattering and cryo-TEM imaging revealed that both the nature of the nucleoside and the position of the squalene moiety relative to the nucleobase determined the self-assembly of the corresponding bioconjugates. It was found that small chemical differences resulted in major differences in the self-organization of nucleolipids when squalene was grafted onto the nucleobase whereas only lamellar phases were observed when squalene was linked to the sugar moiety. The key role of hydrogen bonds between nucleobases in the formation of the lamellar phases was suggested, in agreement with molecular simulations. These findings provide a way to fine tune the supramolecular organization of squalene-based prodrugs, with the aim of improving their pharmacological activity. PMID- 24219057 TI - Transferable mixing of atomistic and coarse-grained water models. AB - Dual-resolution approaches for molecular simulations combine the best of two worlds, providing atomic details in regions of interest and coarser but much faster descriptions of less-relevant parts of molecular systems. Given the abundance of water in biomolecular systems, reducing the computational cost of simulating bulk water without perturbing the solute's properties is a very attractive strategy. Here we show that the coarse-grained model for water called WatFour (WT4) can be combined with any of the three most used water models for atomistic simulations (SPC, TIP3P, and SPC/E) without modifying the characteristics of the atomistic solvent and solutes. The equivalence of fully atomistic and hybrid solvation approaches is assessed by comparative simulations of pure water, electrolyte solutions, and the beta1 domain of streptococcal protein G, for which comparisons between experimental and calculated chemical shifts at (13)Calpha are equivalent. PMID- 24219058 TI - Steric parameters in the Ir-catalyzed regio- and diastereoselective isomerization of primary allylic alcohols. AB - The iridium-catalyzed diastereo- and regioselective isomerization of primary allylic alcohols using Crabtree's catalyst or sterically modified analogs is reported. The importance of the size of the substituents on either the substrates or the catalysts has been rationalized by linear free energy relationships. PMID- 24219060 TI - Effect of hyaluronan tetrasaccharides on epidermal differentiation in normal human epidermal keratinocytes. AB - OBJECTIVE: Hyaluronan (HA) plays a role in keratinocyte proliferation and differentiation. In addition, HA has been shown to have different biological activities depending on its molecular weight. It has been reported that HA mediated CD44 activation regulates keratinocyte differentiation. Therefore, the aim of this study was to investigate the influence of HA tetrasaccharides (HA4) on the regulation of keratinocyte differentiation, CD44 gene expression and CD44 phosphorylated protein in human keratinocytes, and compare HA4 with high molecular weight HA. METHODS: Normal human epidermal keratinocytes (NHEKs) were treated at doses of 1 MUg mL(-1) HA or HA oligosaccharides (HA4). After treatment, cell viability was checked using an MTT (3-(4,5-di-methylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) assay. Each differentiation marker and CD44 mRNA expression was detected by real-time PCR. Each differentiation marker and CD44 phosphorylated protein was assessed by Western blotting. RESULTS: Hyaluronan and HA4 showed no cytotoxicity up to a dose of 1 MUg mL(-1) . On day 3 after HA4 treatment, each differentiation marker mRNA and K10 protein level was higher than that of the control. On day 9, late differentiation marker mRNA and protein levels were increased with HA and HA4 treatment. In addition, HA4 treatment increased the expression of CD44 mRNA, CD44-phosphorylated protein and intracellular calcium concentrations. HA4 enhanced keratinocyte differentiation and increased CD44-phosphorylated protein levels. CONCLUSION: HA4 may induce epidermal differentiation through phosphorylation of CD44. PMID- 24219059 TI - Urinary kidney biomarkers for early detection of nephrotoxicity in clinical drug development. AB - Early detection of drug-induced kidney injury is vital in drug development. Generally accepted biomarkers such as creatinine and blood urea nitrogen (BUN) lack sensitivity and early injury responses are missed. Many new biomarkers to detect nephrotoxicity for pre-clinical utilization have been described and their use is adopted in regulatory guidelines. However, guidance on appropriate biomarkers for clinical trials is minimal. We provide an overview of potentially useful kidney biomarkers that can be used in clinical trials. This includes guidance to select biomarkers suitable to capture specific characteristics of the (expected) kidney injury. We conclude that measurement of urinary kidney injury marker-1 (KIM-1) serves many purposes and is often an appropriate choice. Cystatin C captures effects on glomerular filtration rate (GFR), but this marker should preferably be combined with more specific markers to localize the origin of the observed effect. Untoward effects on tubules can be captured relatively well with several markers. Direct detection of glomerular injury is currently impossible since specific biomarkers are lacking. Indirect assessment of toxic effects on glomeruli is possible by using carefully selected panels of other injury markers. We conclude that it is possible to obtain appropriate information on nephrotoxicity in clinical drug development by using carefully selected panels of injury markers and suggest that identification and validation of specific glomerular biomarkers could be of great value. PMID- 24219061 TI - Bioavailability and stability of intravenous iron sucrose originator versus generic iron sucrose AZAD. AB - CONTEXT: Severe iron deficiency requires intravenous iron supplementation to replenish iron stores. Intravenous iron sucrose has been used for decades for the treatment of anemia. New generic iron sucrose products are now marketed for the use in several countries and there is an ongoing discussion about the safety and efficacy of iron sucrose similars. OBJECTIVE: In this study, we compared the iron sucrose originator Venofer(r) and the generic iron sucrose AZAD (ISA) regarding bioavailability, toxicity and stability in human THP-1 cells and HepG2 cells. METHODS: The bioavailability of Venofer(r) and ISA was investigated in both cell types by a ferrozin-based assay. The release of incorporated iron was assayed by atomic absorption spectroscopy. Ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to investigate the intracellular labile iron pool (LIP), which was measured by the fluorescent calcein assay. The amount of redox-active iron within the iron formulations was assayed using fluorescent dichlorofluorescein. RESULTS: We found no significant differences in all parameters between Venofer(r) and ISA in regard of bioavailability, toxicity and stability in vitro. DISCUSSION: ISA shows identical physico-chemical features and identical bioavailability in vitro. This study is a profound basis for future clinical tests with generic iron sucrose compounds. PMID- 24219062 TI - Synthesis, antibacterial activity, antibacterial mechanism and food applications of ZnO nanoparticles: a review. AB - Bacterial contamination reduces the shelf-life of foods and presents serious risks to human health. Nanotechnology provides the opportunity for the development of new antibacterial agents. Nano-inorganic metal oxides have shown the potential to reduce bacterial contamination of foods. When the particle size of materials decreases from the micrometre to the nanometre range, nano functional properties such as diffusivity, mechanical strength, chemical reactivity and biological properties are improved. Significantly, ZnO has been used in many applications with particular success. Many studies have shown that ZnO nanoparticles have enhanced antibacterial activity. This review discusses the main synthetic methods, antibacterial activity, antibacterial mechanisms and food applications of ZnO nanoparticles. PMID- 24219063 TI - The association between serum vitamin D Level and disease activity in Thai rheumatoid arthritis patients. AB - BACKGROUND: Serum vitamin D level was inversely associated with the risk of developing new onset rheumatoid arthritis (RA) and disease activity, but some conflicting results have been reported. OBJECTIVE: To examine the serum vitamin D status in Thai RA patients and possible independent factors affecting serum 25 hydroxyvitamin vitamin D (25(OH)D) and the associations of serum 25(OH)D level and the disease activity and functional status in Thai RA patients. METHODS: A cross-sectional study was performed in 239 Thai RA patients. The blood levels of 25(OH)D2 and D3 were measured by chemiluminescent immunoassay. Disease activity was assessed according to tender and swollen joint counts, erythrocyte sedimentation rate (ESR), visual analog scale for global patient assessment, Disease Activity Score-28 (DAS-28) and Thai Health Assessment Questionnaire (Thai HAQ). RESULT: The mean vitamin D level was 28.79 ng/mL. There were no associations between 25(OH)D levels and number of tender and swollen joint counts, DAS-28 score, HAQ score or rheumatoid factor (RF) and/or anti-cyclic citrulinated peptide (CCP) positivity. After multivariated analysis, Bangkok residents, non-farmer, obesity and non-vitamin D supplementation were the predictors for vitamin D insufficiency in Thai patients with RA. CONCLUSION: There are no associations of serum 25(OH)D levels with disease activity or functional status in Thai RA patients. The factors associated with vitamin D insufficiency are Bangkok resident, non-farmer, obesity and not taking vitamin D supplementation. PMID- 24219065 TI - The sales and marketing practices of English-language internet alcohol vendors. AB - AIMS: This study aimed to fill information gaps about the sales and marketing practices of internet alcohol vendors and their implications for addressing youth access and other legal violations. Further, it aimed to expand the limited scientific literature on internet alcohol sales using systematic survey methods to inform future efforts to regulate this industry and prevent sales to minors. DESIGN: The design was a cross-sectional website content analysis survey. SETTING: [Not applicable]. PARTICIPANTS: A total of 105 internet alcohol vendor websites. MEASUREMENTS: Six key content analysis topics were explored: products offered, average prices and proportions of vendors using different promotions, policy statements and methods for age verification, payment and delivery. FINDINGS: Websites sell and promote a variety of alcohol products, offered as cheaply as $1.93 for a 750-ml bottle. Vendors rely heavily upon age verification methods that are unlikely to prevent sales to minors. Many vendors advertise shipping of products via methods through which it is illegal or against delivery company policies to transport alcohol, and 99% of vendors accept credit cards. Limiting and enforcing delivery and payment options are types of policy interventions that have been used successfully with internet cigarette vendors that may be applicable to internet alcohol vendors as well. CONCLUSIONS: Internet alcohol vendor practices are insufficient to prevent sales to minors, and need further regulation and enforcement of existing policies. Their sales practices are similar to those of internet cigarette vendors prior to regulation, and similar regulatory approaches may be effective in reducing internet alcohol sales to minors. PMID- 24219066 TI - Words, words, words. PMID- 24219067 TI - Origin of Swedish hemophilia B mutations. AB - BACKGROUND: More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations. OBJECTIVES: To describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)). PATIENTS/METHODS: The registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE. RESULTS: Out of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs. CONCLUSIONS: The association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites. PMID- 24219064 TI - Phosphoinositide 3-kinases upregulate system xc(-) via eukaryotic initiation factor 2alpha and activating transcription factor 4 - A pathway active in glioblastomas and epilepsy. AB - AIMS: Phosphoinositide 3-kinases (PI3Ks) relay growth factor signaling and mediate cytoprotection and cell growth. The cystine/glutamate antiporter system xc(-) imports cystine while exporting glutamate, thereby promoting glutathione synthesis while increasing extracellular cerebral glutamate. The aim of this study was to analyze the pathway through which growth factor and PI3K signaling induce the cystine/glutamate antiporter system xc(-) and to demonstrate its biological significance for neuroprotection, cell growth, and epilepsy. RESULTS: PI3Ks induce system xc(-) through glycogen synthase kinase 3beta (GSK-3beta) inhibition, general control non-derepressible-2-mediated eukaryotic initiation factor 2alpha phosphorylation, and the subsequent translational up-regulation of activating transcription factor 4. This pathway is essential for PI3Ks to modulate oxidative stress resistance of nerve cells and insulin-induced growth in fibroblasts. Moreover, the pathway is active in human glioblastoma cells. In addition, it is induced in primary cortical neurons in response to robust neuronal activity and in hippocampi from patients with temporal lobe epilepsy. INNOVATION: Our findings further extend the concepts of how growth factors and PI3Ks induce neuroprotection and cell growth by adding a new branch to the signaling network downstream of GSK-3beta, which, ultimately, leads to the induction of the cystine/glutamate antiporter system xc(-). Importantly, the induction of this pathway by neuronal activity and in epileptic hippocampi points to a potential role in epilepsy. CONCLUSION: PI3K-regulated system xc(-) activity is not only involved in the stress resistance of neuronal cells and in cell growth by increasing the cysteine supply and glutathione synthesis, but also plays a role in the pathophysiology of tumor- and non-tumor-associated epilepsy by up-regulating extracellular cerebral glutamate. PMID- 24219068 TI - An optimized protocol for overproduction of recombinant protein expression in Escherichia coli. AB - The gram-negative bacterium Escherichia coli (E. coli) offers a means for rapid, high-yield, and economical production of recombinant proteins. Here, a protocol for optimization of parameters involved in bacterial expression conditions is described. L-Asparaginase (ASNase II) was chosen as a model protein for our experiments. ASNase II gene (ansB) was cloned into the pAED4 plasmid and transformed into E. coli BL21pLysS (DE3)-competent cells. It was assumed that high cell density and high copy number of recombinant plasmid in the bacteria host could result in very high production of the recombinant protein. Circumstances for the overproduction of recombinant ASNase II including cell growth conditions, isopropyl beta-D-1-thiogalactopyranoside (IPTG) level, ampicillin (Amp) concentration before and during IPTG induction, and cell density were optimized. Regarding the final optimization, overexpression of ASNase II was assessed on a large scale in LB medium. Periplasmic ASNase II was extracted using an alkaline lysis method. The extracted protein was purified by one-step DEAE Sepharose fast-flow chromatography. ASNase II activity was considered an index for the protein expression. Applying the optimized practical protocol, protein production was significantly enhanced in comparison to the traditional IPTG induction method in the absence of a fermentor and can be applied for overexpression of other recombinant proteins. PMID- 24219069 TI - "At last i've found you". PMID- 24219071 TI - Promoting person-centeredness in long-term care: an exploratory study. AB - This study explored how nursing staff promote person-centeredness in long-term care settings. The study used an anthropological free-listing approach to data collection and qualitative content analysis to analyze written self-report descriptions from a convenience sample of Swedish long-term care staff (N = 436). The analyses resulted in four themes that illuminate how nursing staff promote person-centeredness: Promoting Decision Making, Promoting a Meaningful Living, Promoting a Pleasurable Living, and Promoting Personhood. The study contributes to the literature by providing concrete descriptions of how person-centeredness was facilitated by staff in their everyday practice and contributes to move person-centeredness from the philosophical, policy, and conceptual domains toward clinical implementation. The study also suggests that promoting pleasure for residents is a dimension central to person-centeredness and to health-promoting gerontological nursing, and that "small talk" is an emerging nursing phenomenon that deserves more research attention. PMID- 24219072 TI - Prevalence of pressure ulcers by race and ethnicity for older adults admitted to nursing homes. AB - Little is known about the prevalence of pressure ulcers (PUs) among racial and ethnic groups of older individuals admitted to nursing homes (NHs). NHs admitting higher percentages of minority individuals may face resource challenges for groups with more PUs or ones of greater severity. This study examined the prevalence of PUs (Stages 2 to 4) among older adults admitted to NHs by race and ethnicity at the individual, NH, and regional levels. Results show that the prevalence of PUs in Black older adults admitted to NHs was greater than that in Hispanic older adults, which were both greater than in White older adults. The PU rate among admissions of Black individuals was 1.7 times higher than White individuals. A higher prevalence of PUs was observed among NHs with a lower percentage of admissions of White individuals. [Journal of Gerontological Nursing, 40(3), 20-26.]. PMID- 24219073 TI - Psychiatric illness and resident assaults among veterans in long-term care facilities. AB - This article describes a quality improvement program to reduce the prevalence of physical assaults in a university-affiliated, 234-bed Veterans Affairs (VA) long term care (LTC) facility, which experienced a rise in the number of physical assaults to >4 per 1,000 bed days of care in four LTC units. Analysis of 55 events (29 patients) at this VA LTC site during 2007 revealed 19 resident assailants (8% total population), 10 victims, and 30% repeat events. Of the residents who exhibited assaultive behavior, 44% had dementia and 32% had schizophrenia as a major diagnosis. Following a process improvement plan, new occurrence assaultive behaviors declined from >4 to <1 per 1,000 bed days and remained low during 5-year follow up. PMID- 24219074 TI - Being a cancer caregiver for an older, active, and able woman. PMID- 24219075 TI - The application of Belmont Report principles to policy development. AB - Attention to ethical issues is a routine part of medical research. In this article, we propose that health policy development, like research, include a formal review of these issues. Ethical knowledge is a critical component of epistemology and inherent in development of laws and principles of justice. However, we cannot assume that new policies are subject to a formal ethics review. The Belmont Report of 1978 provides a platform for this process. Prior to the Belmont Report, there was no foundation defining this process in medical research. Based on this history, we propose that health care payment policy development include a formal assessment of risks and benefits using an approach that is familiar to all researchers. PMID- 24219076 TI - Feasibility and effects of TAI CHI for the promotion of sleep quality and quality of life: a single-group study in a sample of older Chinese individuals in Hong Kong. AB - Poor sleep in later life is a global issue that reduces many individuals' quality of life (QOL). The purpose of this pilot study was to test the feasibility and effects of a simplified tai chi exercise intervention on sleep quality and QOL among Chinese community-dwelling older adults with poor sleep quality. This single-group, descriptive feasibility study included 34 individuals with poor sleep quality who agreed to participate in a 12-week tai chi intervention. Twenty six individuals completed the program (23.5% dropout rate). Older adults with poor sleep quality who completed the intervention showed significant improvement in the Medical Outcomes Study Short Form-36 mental component and the Pittsburgh Sleep Quality Index global and component scores. The low recruitment and attendance and high dropout rates might be associated with participants' age, gender, and sleep quality. Further long-term studies are required to examine the potential effects of the tai chi intervention. [Journal of Gerontological Nursing, 40(3), 46-52.]. PMID- 24219077 TI - Sleep disorders in older adults. AB - Sleep pattern changes are considered normal as individuals age. However, changes in sleep patterns can ultimately affect the quality of life of many older adults. In addition, many sleep conditions are associated with an increase in morbidity and mortality. It is essential for clinicians to recognize sleep changes to lead to appropriate treatment. This article will focus on the assessment and interventions of sleep disorders in older adults. PMID- 24219078 TI - Mixing medication into foodstuffs: identifying the issues for paediatric nurses. AB - Medication is often mixed into soft foods to aid swallowing in children. However, this can alter the physical/chemical properties of the active drug. This study reports on the prevalence of the modification procedure, the nature of foodstuffs routinely used and factors which influence how the procedure is performed by nurses working in the National Health Service in Scotland. Mixed methods were employed encompassing an online self-administered questionnaire and semi structured interviews. One hundred and eleven nurses participated, of whom 87% had modified medication prior to administration. Fruit juice (diluted and concentrated) and yoghurts were most commonly used. The interviews (i) identified the limitations of the procedure; (ii) explored the decision-making process; and (iii) confirmed the procedure was a last resort. This study intends to address some of the uncertainty surrounding the medicine modification procedure within the paediatric population. PMID- 24219079 TI - Consumption of purple sweet potato affects post-translational modification of plasma proteins in hamsters. AB - A high level of intake of vegetables is strongly associated with the prevention of chronic diseases. Because post-translational modifications (PTMs) have been shown to be the important biomarkers of the change in physiological functions, this study aimed to explore the changes in PTMs of plasma proteins when purple sweet potato (PSP), a root vegetable, was incorporated into the daily diet. Male Syrian hamsters were maintained on a rice diet (50% rice) or PSP diet (25% rice and 25% PSP) for 12 weeks. Plasma proteins were fractionated by electrophoresis, digested by trypsin, and then separated by nano-liquid chromatography and tandem mass spectrometry. The TurboSequest algorithm was used to identify peptide sequence against the hamster database in Universal Proteins Resource Knowledgebase, and in-house PTM finder programs were used for identification and quantification of PTMs. The results indicated that 95 plasma proteins were identified and 28 PTM sites on 26 of these 95 proteins were affected by consumption of PSP (p < 0.05). Methylation accounted for the largest percentage of affected modifications (35.71%). This study also showed that incorporation of purple sweet potato into the diet significantly lowered blood and liver lipids (p < 0.05). The results of this study provide a basis for prospective studies evaluating the effects of dietary intervention on modifications of proteins. PMID- 24219080 TI - Outcomes of surgical treatment of Peyronie's disease. AB - The aims of the present review were to assess the literature on published outcomes and complications associated with surgical treatments for Peyronie's disease (PD) and to assist clinicians in the effective management of PD by increasing understanding and awareness of the outcomes associated with current surgical treatment options. A PubMed literature search was conducted to identify relevant, peer-reviewed clinical and review articles published between January 1980 and October 2013 related to outcomes of surgical correction of PD. Search terms for this non-systematic review included 'Peyronie's disease', 'outcomes', 'complications', 'erectile dysfunction or ED', 'patient expectation', and 'patient satisfaction'; search terms were searched separately and in combination. Case studies and editorials were excluded, primary manuscripts and reviews were included, and bibliographies of articles of interest were reviewed and key references were obtained. Assessment of the study design, methodology, clinical relevance and impact on the surgical outcomes of PD was performed on the sixty one articles that were selected and analysed. Currently, there are several investigational minimally invasive and non-surgical treatment options for PD; however, surgical treatment remains the standard of care for patients with stable disease and disabling deformity or drug-resistant erectile dysfunction. Each of the different surgical procedures that are used for treatment of PD, including tunical shortening, tunical lengthening (plaque incisions or partial excision and grafting), and use of inflatable penile prostheses, carries its own advantages and disadvantages in terms of potential complications and postoperative satisfaction. Because of the variety of ways that PD may present in affected patients, no single, standard, surgical treatment for this disorder has prevailed and multiple variations of each type of procedure may exist. Surgical outcomes of the most commonly used procedures are not substantially different; therefore, the appropriateness of each treatment option may often depend on disease and patient characteristics (e.g. deformity and erectile function). Surgical algorithms have been published to guide surgeons and patients through the selection of surgical procedures in the absence of conclusive, long-term outcome data. Accumulating data on outcomes associated with established procedures, modifications to these procedures, and new surgical techniques and materials may serve to further guide practice and refine evidence-based selection of the surgical approach. PMID- 24219081 TI - Giant cell arteritis and disseminated tuberculosis: presentation of two cases. PMID- 24219083 TI - Apolipoprotein A-I and adenosine triphosphate-binding cassette transporter A1 expression alleviates lipid accumulation in hepatocytes. AB - BACKGROUND AND AIM: Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to high density lipoprotein apolipoproteins. The lipidation of apolipoprotein A-I (apoA I) by ABCA1 is the rate-limiting step in reverse cholesterol transport and the generation of plasma high density lipoprotein. Here, we examined the effect of apoA-I or ABCA1 overexpression on hepatic lipid levels in BEL-7402 cells. METHODS: Human ABCA1 or apoA-I was overexpressed in BEL-7402 hepatocytes by transfection and human apoA-I was overexpressed via adenoviral vector in C57BL/6J mice with MCD diet. RESULTS: Overexpression of either apoA-I or ABCA1 resulted in an increase in cholesterol efflux and a decrease in cellular fatty acids and triglycerides. However, after repression of ABCA1 by its siRNA, overexpression of apoA-I failed to decrease both cellular fatty acids and triglycerides. ApoA-I or ABCA1 overexpression also resulted in a decrease in the expression of the endoplasmic reticulum stress-related proteins GRP78 and SREBP-1. Overexpression of apoA-I in mice also reduced hepatic lipid levels. CONCLUSIONS: Expression of apoA-I or ABCA1 can reduce steatosis by decreasing lipid storage in hepatocytes through lipid transport and may also reduce endoplasmic reticulum stress, further lessening hepatic steatosis. PMID- 24219084 TI - The effects of spatial contextual familiarity on remembered scenes, episodic memories, and imagined future events. AB - Several recent studies have explored the effect of contextual familiarity on remembered and imagined events. The aim of this study was to examine the extent of this effect by comparing the effect of cuing spatial memories, episodic memories, and imagined future events with spatial contextual cues of varying levels of familiarity. We used real-world landmark cues that had all been previously visited by the participants, and we measured the retrieval time, detail-richness, and vividness of remembered scenes, events, and imagined future events based on these cues. Participants consistently rated scenes and events based on more familiar cues as more detailed and more vivid, and they took less time to retrieve them. When the types of details were examined, it was revealed that the effects of increased contextual familiarity carry over to non-spatial details in the case of remembered events but possibly not in imagined events. This study provides evidence regarding how episodic memory and imagination are reliant on spatial context and possibly the process of scene construction. PMID- 24219085 TI - Embodiment during reading: Simulating a story character's linguistic actions. AB - According to theories of embodied cognition, a critical element in language comprehension is the formation of sensorimotor simulations of the actions and events described in a text. Although much of the embodied cognition research has focused on simulations of motor actions, we ask whether readers form simulations of story characters' linguistic actions. For example, when a character is described as speaking, do readers form an auditory image of the character's words? Furthermore, if a character is described as reading, do readers form a visual image of the words on the page? In 4 experiments, a character was described as either reading or speaking, quickly or slowly. Critically, participants either read silently or read aloud so that their action matched or mismatched the character's action. Consistent with the action-sentence compatibility effect (Glenberg & Kaschak, 2002), only when the participant's and the character's actions matched--when both were reading or both were speaking- was a rate effect found, with participants reading/speaking more slowly when the character was described as reading/speaking slowly. We conclude that comprehension of a character's linguistic action involves the same types of sensorimotor simulations as have been shown across a vast array of other types of actions. PMID- 24219082 TI - Association between funding source, methodological quality and research outcomes in randomized controlled trials of synbiotics, probiotics and prebiotics added to infant formula: a systematic review. AB - BACKGROUND: There is little or no information available on the impact of funding by the food industry on trial outcomes and methodological quality of synbiotics, probiotics and prebiotics research in infants. The objective of this study was to compare the methodological quality, outcomes of food industry sponsored trials versus non industry sponsored trials, with regards to supplementation of synbiotics, probiotics and prebiotics in infant formula. METHODS: A comprehensive search was conducted to identify published and unpublished randomized clinical trials (RCTs). Cochrane methodology was used to assess the risk of bias of included RCTs in the following domains: 1) sequence generation; 2) allocation concealment; 3) blinding; 4) incomplete outcome data; 5) selective outcome reporting; and 6) other bias. Clinical outcomes and authors' conclusions were reported in frequencies and percentages. The association between source of funding, risk of bias, clinical outcomes and conclusions were assessed using Pearson's Chi-square test and the Fisher's exact test. A p-value < 0.05 was statistically significant. RESULTS: Sixty seven completed and 3 on-going RCTs were included. Forty (59.7%) were funded by food industry, 11 (16.4%) by non industry entities and 16 (23.9%) did not specify source of funding. Several risk of bias domains, especially sequence generation, allocation concealment and blinding, were not adequately reported. There was no significant association between the source of funding and sequence generation, allocation concealment, blinding and selective reporting, majority of reported clinical outcomes or authors' conclusions. On the other hand, source of funding was significantly associated with the domains of incomplete outcome data, free of other bias domains as well as reported antibiotic use and conclusions on weight gain. CONCLUSION: In RCTs on infants fed infant formula containing probiotics, prebiotics or synbiotics, the source of funding did not influence the majority of outcomes in favour of the sponsors' products. More non-industry funded research is needed to further assess the impact of funding on methodological quality, reported clinical outcomes and authors' conclusions. PMID- 24219086 TI - Base rates: both neglected and intuitive. AB - Base-rate neglect refers to the tendency for people to underweight base-rate probabilities in favor of diagnostic information. It is commonly held that base rate neglect occurs because effortful (Type 2) reasoning is required to process base-rate information, whereas diagnostic information is accessible to fast, intuitive (Type 1) processing (e.g., Kahneman & Frederick, 2002). To test this account, we instructed participants to respond to base-rate problems on the basis of "beliefs" or "statistics," both in free time (Experiments 1 and 3) and under a time limit (Experiment 2). Participants were given problems with salient stereotypes (e.g., "Jake lives in a beautiful home in a posh suburb") that either conflicted or coincided with base-rate probabilities (e.g., "Jake was randomly selected from a sample of 5 doctors and 995 nurses for conflict; 995 doctors and 5 nurses for nonconflict"). If utilizing base-rates requires Type 2 processing, they should not interfere with the processing of the presumably faster belief based judgments, whereas belief-based judgments should always interfere with statistics judgments. However, base-rates interfered with belief judgments to the same extent as the stereotypes interfered with statistical judgments, as indexed by increased response time and decreased confidence for conflict problems relative to nonconflict. These data suggest that base-rates, while typically underweighted or neglected, do not require Type 2 processing and may, in fact, be accessible to Type 1 processing. PMID- 24219087 TI - Testing the item-order account of design effects using the production effect. AB - A number of memory phenomena evident in recall in within-subject, mixed-lists designs are reduced or eliminated in between-subject, pure-list designs. The item order account (McDaniel & Bugg, 2008) proposes that differential retention of order information might underlie this pattern. According to this account, order information may be encoded when a common form of processing is used alone in a list (e.g., reading), but not when an unusual form of processing is used (e.g., generation) or when a common form and an unusual form are mixed within a list. The production effect--better memory for words said aloud than for words read silently--shows this same design-contingent pattern. In 2 experiments, we investigated whether differential order retention might underlie the production effect. Consistent with the item-order account, we found that retention of order information was better in pure silent lists than in either pure aloud lists or mixed lists, as measured using an order reconstruction test. Moreover, in Experiment 2, order was better preserved in free recall of pure silent lists than of either pure aloud or mixed lists. Thus, production joins the set of tasks identified by McDaniel and Bugg (2008), and our findings suggest a role for order processing in explaining the production effect. PMID- 24219089 TI - Does the acceptable noise level (ANL) predict hearing-aid use? AB - OBJECTIVE: It has been suggested that individuals have an inherent acceptance of noise in the presence of speech, and that different acceptance of noise results in different hearing-aid (HA) use. The acceptable noise level (ANL) has been proposed for measurement of this property. It has been claimed that the ANL magnitude can predict hearing-aid use patterns. Many papers have been published reporting on different aspects of ANL, but none have challenged the predictive power of ANL. The purpose of this study was to discuss whether ANL can predict HA use and how more reliable ANL results can be obtained. DESIGN: Relevant literature regarding the ANL was found on Medline, Embase, and Google Scholar. Additional information was found as references in the included papers and through personal contacts, for instance when attending audiology conferences. STUDY SAMPLE: Forty-five papers published in peer reviewed journals as well as a number of papers from trade journals, posters and oral presentations from audiology conventions. CONCLUSIONS: An inherent acceptance of noise in the presence of speech may exist, but no method for precise measurement of ANL is available. The ANL model for prediction of HA use has yet to be proven valid. PMID- 24219090 TI - The ANL: does it, or does it not? PMID- 24219091 TI - Feasibility of haloperidol-anchored albumin nanoparticles loaded with doxorubicin as dry powder inhaler for pulmonary delivery. AB - Haloperidol (Hal) is a ligand that can target sigma 2 receptors over-expressed in non-small cell lung cancer. Hal targeted nanoparticles of bovine serum albumin (BSA) were prepared for pulmonary delivery of doxorubicin (DOX). The conjugation was confirmed by Fourier transform infrared spectroscopy (FTIR) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic methods. Nanoparticles were prepared by desolvation method from BSA-Hal and were loaded with DOX. They were characterized for their morphology, particle size, zeta potential, drug loading and release efficiency. The optimized nanoparticles were spray-dried using trehalose, l-leucin and mannitol as dry powder inhaler (DPI) in different inlet temperatures between 80 and 120 degrees C. The obtained nanocomposites were characterized for their aerodynamic diameter, specific surface area (cm(2)/g) and fine particle fraction (FPF) by a Cascade Impactor device. The optimized nanoparticles showed particle size of 218 nm, zeta potential of -25.4 mV, drug entrapment efficiency of 89% and release efficiency of 56% until 2 h. After spray drying of these nanoparticles, the best results were obtained from mannitol with an inlet temperature of 80 degrees C which produced a mean aerodynamic diameter of 4.58 MUm, FPF of 66% and specific surface area of 6302.99 cm(2)/g. The obtained results suggest that the designed DPI could be a suitable inhaler for targeted delivery of DOX in pulmonary delivery. PMID- 24219093 TI - Rapid degradation of Deepwater Horizon spilled oil by indigenous microbial communities in Louisiana saltmarsh sediments. AB - The Deepwater Horizon oil spill led to the severe contamination of coastal environments in the Gulf of Mexico. A previous study detailed coastal saltmarsh erosion and recovery in a number of oil-impacted and nonimpacted reference sites in Barataria Bay, Louisiana over the first 18 months after the spill. Concentrations of alkanes and polyaromatic hydrocarbons (PAHs) at oil-impacted sites significantly decreased over this time period. Here, a combination of DNA, lipid, and isotopic approaches confirm that microbial biodegradation was contributing to the observed petroleum mass loss. Natural abundance (14)C analysis of microbial phospholipid fatty acids (PLFA) reveals that petroleum derived carbon was a primary carbon source for microbial communities at impacted sites several months following oil intrusion when the highest concentrations of oil were present. Also at this time, microbial community analysis suggests that community structure of all three domains has shifted with the intrusion of oil. These results suggest that Gulf of Mexico marsh sediments have considerable biodegradation potential and that natural attenuation is playing a role in impacted sites. PMID- 24219094 TI - Stick-Slip to Sliding Transition of Dynamic Contact Lines under AC Electrowetting. AB - We show that at low velocities the dynamics of a contact line of a water drop moving over a Teflon-like surface under ac electrowetting must be described as stick-slip motion, rather than one continuous movement. At high velocities we observe a transition to a slipping regime. In the slipping regime the observed dependence of the contact angle is well described by a linearization of both the hydrodynamic and the molecular-kinetic model for the dynamic contact line behavior. The overall geometry of the drop also has a strong influence on the contact angle: if the drop is confined to a disk-like shape with radius R, much larger than the capillary length, and height h, smaller than the capillary length, the advancing angle increases steeper with velocity as the aspect ratio h/R is smaller. Although influence of the flow field near a contact line on the contact angle behavior has also been observed in other experiments, these observations do not fit either model. Finally, in our ac experiments no sudden increase of the hysteresis beyond a certain voltage and velocity was observed, as reported by other authors for a dc voltage, but instead we find with increasing voltage a steady decrease of the hysteresis. PMID- 24219092 TI - Bioreducible polycations as shuttles for therapeutic nucleic acid and protein transfection. AB - SIGNIFICANCE: Nucleic acids such as gene-encoding DNAs, gene-silencing small interfering RNAs, or recombinant proteins addressing intracellular molecular targets present a major new therapeutic modality, provided efficient solutions for intracellular delivery can be found. The different physiological redox environments inside and outside the cell can be utilized for optimizing the involved transport processes. RECENT ADVANCES: Intracellular delivery of nucleic acids or proteins requires dynamic carriers that discriminate between different cellular locations. Bioreducible cationic polymers can package their therapeutic cargo stably in the extracellular environment, but sense the reducing intracellular cytosolic environment. Based on disulfide cleavage, carriers are degraded into biocompatible fragments and release the cargo in functional form. Disulfide linkages between oligocations, between the carrier and the cargo, or spatial caging of complexed cargo by disulfides have been pursued, with polymers or precise sequence-defined peptides and oligomers. CRITICAL ISSUES: A quantitative knowledge of the bioreductive capacities within different biological compartments and the involved cellular reduction processes would be greatly helpful for improved carriers with disulfides cleaved within the right compartment at the right time. FUTURE DIRECTIONS: Novel designs of multifunctional nanocarriers will incorporate macromolecular disulfide entry mechanisms previously optimized by natural evolution of toxins and viruses. In addition to extracellular stabilization and intracellular disassembly, tuned disulfides will contribute to deshielding at the cell surface, or translocation from intracellular compartments to the cytosol. PMID- 24219095 TI - Non-peptide-based fluorogenic small-molecule probe for elastase. AB - Human neutrophil elastase (HNE) has been identified as a potential therapeutic target for the discovery of anti-inflammatory drugs for decades. However, little progress has been made on assays measuring the activity of HNE, especially on synthetic substrates which play essential role in determination of HNE activity. Herein, a small-molecule compound, 2,2,3,3,3-pentafluoro-N-(2-oxo-4 (trifluoromethyl)-2H-chromen-7-yl)-propanamide (compound 4), has been successfully designed as the first ever non-peptide-based fluorogenic substrate for HNE. A "turn-on" fluorometric assay based on 4 has been successfully developed for rapid determination of HNE activity and the inhibitory kinetic study. Most importantly, the probe 4 shows highly specific response for HNE among seven tested hydrolases or proteins and can be directly used to detect the elevated HNE activity in the serum of chronic obstructive pulmonary disease (COPD) patients compared to that of healthy controls. This specific and cost effective probe will facilitate future high-throughput discovery of HNE inhibitors and clinical diagnosis of elastase-related diseases. PMID- 24219097 TI - Inkjet-printing-based soft-etching technique for high-speed polymer ambipolar integrated circuits. AB - Here, we report the so-called soft-etching process based on an inkjet-printing technique for realizing high-performance printed and flexible organic electronic circuits with conjugated polymer semiconductors. The soft-etching process consists of selective etching of the gate made of a dielectric polymer and deposition of another gate dielectric layer. The method enables the use of a more desirable polymer dielectric layer for the p-channel and n-channel organic field effect transistors (OFETs) in complementary integrated circuits. We fabricated high-performance ambipolar complementary inverters and ring oscillators (ROs) using poly([N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6 diyl]-alt-5,5'-(2,2'-bithiophene)) (P(NDI2OD-T2)) as the active layer as well as poly(vinylidenefluoride-trifluoroethylene) (P(VDF-TrFE)) and polystyrene ((PS)/P(VDF-TrFE)) as dielectric materials for the p-channel (pull-up transistor) and n-channel (pull-down transistor) OFETs, respectively. The PS dielectric polymer was selectively etched by inkjetting of n-butyl acetate as an orthogonal solvent for P(NDI2OD-T2). Employing this methodology, the five-stage ambipolar ROs with P(NDI2OD-T2) exhibited an oscillation frequency of ~16.7 kHz, which was much higher than that of non-soft-etched ROs with a single dielectric layer (P(VDF-TrFE); ~3 kHz). PMID- 24219096 TI - Tumor lysate-loaded biodegradable microparticles as cancer vaccines. AB - Cancer vaccines that use tumor lysate (TL) as a source of tumor-associated antigens (TAAs) have significant potential for generating therapeutic anti-tumor immune responses. Vaccines encompassing TL bypass the limitations of single antigen vaccines by simultaneously stimulating immunity against multiple TAAs, thereby broadening the repertoire of TAA-specific T-cell clones available for activation. Administration of TL in particulate form, such as when encapsulated in biodegradable microparticles, increases its immunostimulatory capacity and produces more robust immune responses than when TL is given in soluble form. These effects can be further enhanced by co-administering TL with adjuvants. A number of recent studies using polymeric microparticle delivery of TL, with or without adjuvants, have produced promising results in preclinical studies. In this review, we will discuss current experimental approaches involving TL being pursued in the oncoimmunology field, and comment on strategies such as combining specific chemotherapeutic agents with TL microparticle delivery that may eventually lead to improved survival outcomes for cancer patients. PMID- 24219098 TI - A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia. AB - BACKGROUND: Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. METHODS: 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants' predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. RESULTS: Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants' affect. CONCLUSIONS: Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202). PMID- 24219099 TI - Zinc(II)-regulation of hydrazone switch isomerization kinetics. AB - The extra H-bond in a bipyridyl-functionalized hydrazone rotary switch slows down its Z->E isomerization rate by 2 orders of magnitude (k = (3.5 +/- 0.2) * 10(-6) s(-1)). The coordination of Zn(2+) with the bipyridyl subgroup simultaneously 'unlocks' this H-bond and accelerates the isomerization rate by at least 6 orders of magnitude (k > 6.9 s(-1)). This coordination-regulated kinetic control could open the way to molecular timers that can be used in guiding temporal events. PMID- 24219100 TI - High prevalence of oqxAB in Escherichia coli isolates from domestic and wild lagomorphs in Italy. AB - This study aimed to identify and characterize class 1 and 2 integrons and plasmid mediated quinolones resistance (PMQR) genes in a collection of 113 multidrug resistance (MDR) Escherichia coli isolated from farm and wild lagomorphs between 2006 and 2008 in Northern Italy. Strains were examined for antimicrobial susceptibility by agar disk diffusion method and E-test for colistin (COL); integrons and gene cassettes content by real-time polymerase chain reaction (PCR) and DNA sequencing; PMQR genes by PCR and DNA sequencing; clonal relatedness by multilocus sequence typing; and plasmids by PCR-based replicon typing. Class 1 integrons were detected in 69 isolates (47 farm rabbits, 14 wild rabbits, and 8 wild hares). No class 2 integrons were found. Five different gene cassettes arrays were identified (aadA1, dfrA1-aadA1, orf in682-dhfrA5, orf in682-dfrA5 orfD ins21, and dfrA17-aadA5). Fifteen percent (17/113) of isolates carried oqxAB, no other PMQR determinants. All but one oqxAB-positive E. coli strains were recovered from farm rabbits. Seven out of 17 strains were associated with the predominant ST238 and carried from three to six different plasmid types, such as IncF, IncHI1, IncI1, IncN, IncP, IncX1, IncY, and ColE. COL resistance was identified in 6/113 strains (5.3%). This study provides new insights on the resistance phenotypes and the prevalence and dissemination of oqxAB in E. coli from farm and wild lagomorphs, suggesting that these animals may be reservoir of these genetic determinants in Italy and thus a potential source of PMQR E. coli for humans. PMQR mediated by oqxAB has not been detected in farm and wild lagomorphs before. PMID- 24219101 TI - The evidentiary value of challenge trials for three pre-harvest food safety topics: a systematic assessment. AB - Reducing zoonotic pathogens in food animals prior to harvest will reduce the pathogen burden that enters the food chain and the environment. Consequently, the burden of enteric illness in humans may be reduced. Evaluating interventions to reduce a pathogen in animals often begins with challenge trials, in which animals are deliberately exposed to the pathogen under controlled conditions. Challenge trials are subsequently followed by field trials, also known as randomized controlled trials, in which the animals are naturally exposed to the pathogen. Challenge trials can most effectively inform field trials only if they precede field trials, are robust, internally valid and transparently reported. Using systematic review and meta-analysis methodology, we examined the pre-harvest food safety literature for three intervention-pathogen-species combinations: probiotics/competitive exclusion products in ruminants to reduce Escherichia coli O157 shedding, vaccines in ruminants to reduce E. coli O157 shedding and vaccines in swine to reduce Salmonella shedding. We examined two outcomes, prevalence of faecal shedding at the end of the trial and prevalence of faecal shedding throughout the trial period, to compare challenge trials and field trials. We found that challenge trials occurred concurrently with field trials, challenge trials suffered from reporting deficiencies of methodological features, challenge trials tended to report a more favourable outcome than field trials, and there was some evidence of publication bias among all three intervention-pathogen species combinations. Challenge trials would better serve to inform field trials if they precede field trials, are methodologically sound, include transparent reporting and are published regardless of their results. In addition, due to our findings of greater efficacy reported among challenge trials compared with field trials, risk models predicting the public health benefits of pre-harvest interventions to reduce zoonotic pathogens in livestock might be best served by field trial results alone. PMID- 24219102 TI - Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. AB - AIMS: The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature. METHODS: The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate <=21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium <=3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate. CONCLUSIONS: Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia. PMID- 24219104 TI - A test for community saturation along the Himalayan bird diversity gradient, based on within-species geographical variation. AB - The idea that ecological communities are unsaturated is central to many explanations for regional gradients in species diversity. We describe a test for differing degrees of saturation across a regional diversity gradient, based on within-species geographical variation in ecological attributes. If communities in species-poor regions are less saturated than communities in species-rich regions, species that straddle both regions should have broader niches in species-poor regions, exploiting resources that are consumed by other species in species-rich regions. We studied 10 species of Old World leaf warblers that range across the Himalayas. Elevational range and feeding method showed niche contractions in the species-poor north-west Himalayas with respect to the species-rich south-east Himalayas, whereas prey size did not vary geographically. Niche contractions are contrary to the expectation of character release in depauperate environments, as has been shown, for example in mainland-island comparisons. We show that arthropod abundances are likely a limiting resource, and that niche contractions are consistent with measurements of a narrowing of resource availability. Results suggest that north-western warbler communities are at least as saturated as the south-east and that lower resource diversity drives reduced species numbers. PMID- 24219105 TI - Abstracts of the Third International Conference on Reproductive Immunology. September 28-30, 2013. Shanghai, China. PMID- 24219103 TI - Four-and-a-half LIM domains proteins are novel regulators of the protein kinase D pathway in cardiac myocytes. AB - PKD (protein kinase D) is a serine/threonine kinase implicated in multiple cardiac roles, including the phosphorylation of the class II HDAC5 (histone deacetylase isoform 5) and thereby de-repression of MEF2 (myocyte enhancer factor 2) transcription factor activity. In the present study we identify FHL1 (four-and a-half LIM domains protein 1) and FHL2 as novel binding partners for PKD in cardiac myocytes. This was confirmed by pull-down assays using recombinant GST fused proteins and heterologously or endogenously expressed PKD in adult rat ventricular myocytes or NRVMs (neonatal rat ventricular myocytes) respectively, and by co-immunoprecipitation of FHL1 and FHL2 with GFP-PKD1 fusion protein expressed in NRVMs. In vitro kinase assays showed that neither FHL1 nor FHL2 is a PKD1 substrate. Selective knockdown of FHL1 expression in NRVMs significantly inhibited PKD activation and HDAC5 phosphorylation in response to endothelin 1, but not to the alpha1-adrenoceptor agonist phenylephrine. In contrast, selective knockdown of FHL2 expression caused a significant reduction in PKD activation and HDAC5 phosphorylation in response to both stimuli. Interestingly, neither intervention affected MEF2 activation by endothelin 1 or phenylephrine. We conclude that FHL1 and FHL2 are novel cardiac PKD partners, which differentially facilitate PKD activation and HDAC5 phosphorylation by distinct neurohormonal stimuli, but are unlikely to regulate MEF2-driven transcriptional reprogramming. PMID- 24219106 TI - When is research clinical advice? Interpreting an exploratory study of paracetamol overdose. PMID- 24219108 TI - Room-temperature synthesis of trisubstituted allenylsilanes via regioselective C H functionalization. AB - A Rh(III)-catalyzed o-C-H bond functionalization-based allenylation reaction of allenylsilanes 2 with N-methoxybenzamides 1 affords poly-substituted allenylsilanes with a wide range of attractive functional groups in moderate to excellent yields under very mild conditions (20 degrees C, compatible with ambient air and moisture). Those products may be transformed to different products with attractive structural features. Careful mechanistic studies suggest the reaction proceeds via o-rhodation, regioselective insertion, and beta-H elimination. PMID- 24219107 TI - Letter in response to Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. PMID- 24219109 TI - Thai nurses' perspectives on the use of complementary and alternative medicine among Thai breast cancer survivors in northern Thailand. AB - Breast cancer survivors are more likely to seek complementary and alternative medicine (CAM) for their health and well-being than other cancer patients. The purpose of the study was to describe how Thai nurses perceive the use of CAM in Thai breast cancer survivors. An ethno-nursing research method was used. Fifteen Thai nurses who had experience in taking care of Thai breast cancer survivors who used CAM from a tertiary care referral and resource centre in the lower northern part of Thailand were interviewed. Two major themes emerged from this study: Meaning of care practices in CAM was seen as: (i) an additional beneficial choice for health; and (ii) emotional and psychological healing. Nurses should be concerned about CAM use in Thai breast cancer survivors. Open communication about CAM helps ensure that safe and holistic care is provided. Further research to enhance integration of CAM into health care is needed. PMID- 24219110 TI - Association of hospital volume with conditional 90-day mortality after cystectomy: an analysis of the National Cancer Data Base. AB - OBJECTIVE: To examine the association of hospital volume and 90-day mortality after cystectomy, conditional on survival for 30 days. PATIENTS AND METHODS: The National Cancer Data Base was used to evaluate 30- and 90-day mortality for 35,055 patients who underwent cystectomy for bladder cancer at one of 1118 hospitals. Patient data were aggregated into hospital volume categories based on the mean annual number of procedures (low-volume hospital: <10 procedures; intermediate-volume hospital: 10-19 procedures; high-volume hospital: >=20 procedures). Associations between mortality and clinical, demographic and hospital characteristics were analysed using hierarchical logistic regression models. To assess the association between hospital volume and 90-day mortality independently of shorter-term mortality, 90-day mortality conditional on 30-day survival was assessed in the multivariate modelling. RESULTS: Unadjusted 30- and 90-day mortality rates were 2.7 and 7.2% overall, 1.9 and 5.7% among high-volume hospitals, and 3.2 and 8.0% among low-volume hospitals, respectively. Compared with high-volume hospitals, the adjusted risks among low-volume hospitals (odds ratio [95% CI]) of 30- and 90-day mortality, conditional on having survived for 30 days, from the hierarchical models were 1.5 (1.3-1.9), and 1.2 (1.0-1.4), respectively. CONCLUSIONS: A low hospital volume was associated with greater 30- and 90-day mortality. These data support the need for further research to better understand the relatively high mortality rates seen between 30 and 90 days, which are high and less variable across hospital volume strata. The stronger association between volume and 30-day mortality suggests that quality-reporting efforts should focus on shorter-term outcomes. PMID- 24219111 TI - Angiotensin-converting enzyme inhibitory effects by plant phenolic compounds: a study of structure activity relationships. AB - In this study, 22 phenolic compounds were investigated to inhibit the angiotensin converting enzyme (ACE). Tannic acid showed the highest activity (IC50 = 230 MUM). The IC50 values obtained for phenolic acids and flavonoids ranged between 0.41 and 9.3 mM. QSAR analysis confirmed that the numbers of hydroxyl groups on the benzene ring play an important role for activity of phenolic compounds and that substitution of hydroxyl groups by methoxy groups decreased activity. Docking studies indicated that phenolic acids and flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. Other compounds, such as resveratrol and pyrogallol, may inhibit ACE via interactions with amino acids at the active site, thereby blocking the catalytic activity of ACE. These structure function relationships are useful for designing new ACE inhibitors and potential blood-pressure-lowering compounds based on phenolic compounds. PMID- 24219113 TI - The chlamydia knowledge, awareness and testing practices of Australian general practitioners and practice nurses: survey findings from the Australian chlamydia control effectiveness pilot (ACCEPt). AB - BACKGROUND: ACCEPt, a large cluster randomized control trial, aims to determine if annual testing for 16 to 29 year olds in general practice can reduce chlamydia prevalence. ACCEPt is the first trial investigating the potential role of practice nurses (PN) in chlamydia testing. To inform the design of the ACCEPt intervention, we aimed to determine the chlamydia knowledge, attitudes, and testing practices of participating general practitioners (GPs) and PNs. METHODS: GPs and PNs from 143 clinics recruited from 52 areas in 4 Australian states were asked to complete a survey at time of recruitment. Responses of PNs and GPs were compared using conditional logistic regression to account for possible intra cluster correlation within clinics. RESULTS: Of the PNs and GPs enrolled in ACCEPt, 81% and 72% completed the questionnaire respectively. Less than a third of PNs (23%) and GPs (32%) correctly identified the two age groups with highest infection rates in women and only 16% vs 17% the correct age groups in men. More PNs than GPs would offer testing opportunistically to asymptomatic patients aged <=25 years; women having a pap smear (84% vs 55%, P<0.01); antenatal checkup (83% vs 44%, P<0.01) and Aboriginal men with a sore throat (79% vs 33%, P<0.01), but also to patients outside of the guideline age group at the time of the survey; 26 year old males presenting for a medical check (78% vs 30%, P = <0.01) and 33 year old females presenting for a pill prescription (83% vs 55%, P<0.01). More PNs than GPs knew that retesting was recommended after chlamydia treatment (93% vs 87%, P=0.027); and the recommended timeframe was 3 months (66% vs 26%, P<0.01). A high proportion of PNs (90%) agreed that they could conduct chlamydia testing in general practice, with 79% wanting greater involvement and 89% further training. CONCLUSIONS: Our survey reveals gaps in chlamydia knowledge and management among GPs and PNs that may be contributing to low testing rates in general practice. The ACCEPt intervention is well targeted to address these and support clinicians in increasing testing rates. PNs could have a role in increasing chlamydia testing. PMID- 24219115 TI - Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers. AB - BACKGROUND AND AIM: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological, and metabolic factors. METHODS: Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (>= F2) was defined as stiffness > 7.5 kPa, and probable cirrhosis as > 11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses. RESULTS: Ninety-six CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2 +/- 2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, P < 0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8 27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced high density lipoprotein cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, hepatitis B virus DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis. CONCLUSION: Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population. PMID- 24219116 TI - Evaluation of handling and reuse approaches for the waste generated from MEA based CO2 capture with the consideration of regulations in the UAE. AB - A waste slip-stream is generated from the reclaiming process of monoethanolamine (MEA) based Post-Combustion Capture (PCC). It mainly consists of MEA itself, ammonium, heat-stable salts (HSS), carbamate polymers, and water. In this study, the waste quantity and nature are characterized for Fluor's Econamine FGSM coal fired CO2 capture base case. Waste management options, including reuse, recycling, treatment, and disposal, are investigated due to the need for a more environmentally sound handling. Regulations, economic potential, and associated costs are also evaluated. The technical, economic, and regulation assessment suggests waste reuse for NOx scrubbing. Moreover, a high thermal condition is deemed as an effective technique for waste destruction, leading to considerations of waste recycling into a coal burner or incineration. As a means of treatment, three secondary-biological processes covering Complete-Mix Activated Sludge (CMAS), oxidation ditch, and trickling filter are designed to meet the wastewater standards in the United Arab Emirates (UAE). From the economic point of view, the value of waste as a NOx scrubbing agent is 6,561,600-7,348,992 USD/year. The secondary-biological treatment cost is 0.017-0.02 USD/ton of CO2, while the cost of an on-site incinerator is 0.031 USD/ton of CO2 captured. In conclusion, secondary biological treatment is found to be the most economical option. PMID- 24219117 TI - Decisional balance among potential implantable cardioverter defibrillator recipients: development of the ICD-decision analysis scale (ICD-DAS). AB - INTRODUCTION: Sudden cardiac death is a well-documented public health problem and the implantable cardioverter defibrillator (ICD) has demonstrated benefit in reducing mortality. Prospective patients must identify and evaluate the ICD's pros and cons and produce a personal decision. The purpose of this study was to create and evaluate a measure of patient-evaluated pros and cons of the ICD, and its relationship to patient decision regarding ICD implantation. METHODS AND RESULTS: The ICD-decision analysis scale (ICD-DAS) was created and tested in prospective ICD recipients (N = 104). Factor analysis was performed to evaluate interitem relationships, and subsequently, identified subscales; additional psychosocial measures were used to predict the ICD decision. A two-factor measure for ICD decision making was established with two subscales: ICD Pros and ICD Cons. The subscales have high internal consistency and were strong predictors of intent to choose an ICD. Other psychosocial measures were not significantly predictive of ICD Choice, yet simultaneous entry of ICD Pros and Cons subscales resulted in a significant increase in R(2) , F(2, 59) = 19.36, P < 0.001. The full model was significantly greater than zero, F(11, 70) = 5.017, P < 0.001, R(2) = 0.48. CONCLUSION: The ICD-DAS provides the first empirically tested and clinically useful approach to understanding the specific pros and cons for prospective ICD patients. The measure can assist clinicians with patient-centered discussions regarding sudden cardiac arrest treatments. The ICD-DAS will allow for the provision of tailored education or counseling and may be used to predict postdecision outcomes. PMID- 24219114 TI - Extracellular matrix and liver disease. AB - SIGNIFICANCE: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. CRITICAL ISSUES: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. RECENT ADVANCES: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF' apoptosis, senescence, and reversal to quiescence. FUTURE DIRECTIONS: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new "omics" tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. PMID- 24219118 TI - Ordered honeycomb structural interfaces for anticancer cells growth. AB - The patterned honeycomb structure film with the aggregation-induced emission property was prepared successfully by the breath figure method and photopolymerization method. Characterization of the HeLa and HepG2 cell culture on this surface indicates the porous honeycomb structures show anticancer cells growth function. So this kind of honeycomb structure will be promising for the control of cancer cell growth behaviors and achieving the application of anticancer. PMID- 24219119 TI - Modification of an amplification reaction in recursively dynamic compartments driven by stirring. AB - In living systems, biochemical reactions are confined to cellular or subcellular compartments, such as the plasma membrane and the organelles within a cell. These biological compartments are usually subjected to recursive changes, such as combinations of growth, fusion, and division, to constitute repeating cell cycles. In such recursively dynamic compartments, the encapsulated biochemical reaction may exhibit dynamics that differ from those of the static compartment (i.e., test tubes) used in conventional biochemistry experiments. To test this hypothesis in a simplified model, we mechanically stirred femtoliter-sized water in-oil emulsion droplets so that individual droplets were subjected to repeated coalescence and breakage. We show that recursive dynamics appeared in the emulsion, which were measured by the exponential propagation of a water-soluble dye. The rate of the propagation, MU, was controlled by modulating the pulse width of stirring in an electromagnetic stirrer. Within this system, we studied the dynamics of an RNA-amplification reaction in recursively increasing reaction compartments at various values of MU. We showed that there was an optimal value of MU that maximized RNA amplification. This effect was explained by the balance between the opposing effects of supply of substrate and the dilution of amplified RNA both resulting from coalescence. Moreover, when we mixed two RNA species with different kinetic properties, we found a preferential amplification for one of the species only in the recursively dynamic emulsion. This effect was partly explained by a separation effect which preferentially amplifies the number of compartments for the molecular specie that can better follow the breakage dynamics of the compartments. The present work demonstrated how the recursive dynamics of compartments modifies the internal biochemical reaction. PMID- 24219120 TI - Nd:YAG laser irradiation of the tooth root surface inhibits demineralization and root surface softening caused by minocycline application. AB - OBJECTIVE: The aim of this study was to investigate the effect of laser irradiation on root surface demineralization caused by local drug delivery systems (DDS), and to evaluate the effect of sealing on drug retention. BACKGROUND DATA: The duration of supportive periodontal treatment (SPT) has increased with increasing life expectancy. Repeated root planing and DDS application during SPT should be reconsidered with regard to their effects on the root surface. METHODS: Extracted human teeth were collected, cut into 3 * 3 * 2 mm root dentin specimens, and divided randomly into eight groups with various combinations of Nd:YAG laser power (0, 0.5, 1, and 2 W), with and without DDS (minocycline HCl). Specimen microhardness and calcium (Ca) solubility were measured after treatment. The specimens (control and laser and DDS groups) were examined by scanning electron microscopy. Forty SPT patients were recruited, to assess the effect of periodontal pocket sealing on drug retention. RESULTS: Laser irradiation increased the microhardness of root specimens in an energy-dependent manner. Calcium solubilities decreased from the 0 W+DDS group to the 2.0 W+DDS group. The mean Ca solubilities in the 1.0 W+DDS and 2.0 W+DDS groups were significantly lower than in the 0 W+DDS group (p<0.01, p<0.001, respectively). Laser irradiation counteracted the softening effect of DDS. Morphologic change was observed in the 2 W+DDS group; however, no morphologic changes were observed in the control and the 1 W+DDS groups. The mean concentration of minocycline in the periodontal pocket 24 h after application was 252.79 +/- 67.50 MUg/mL. CONCLUSIONS: Laser irradiation of the root surface inhibited the softening and decalcification caused by minocycline HCl. Sealing the periodontal pockets effectively improved drug retention. These results suggest that the combination of laser irradiation and DDS could benefit patients receiving repeated SPT. PMID- 24219121 TI - Automated auditory response detection: Improvement of the statistical test strategy. AB - OBJECTIVE: Automated auditory response detection is always performed by applying an appropriate statistical test to a sample of stimulus-related epochs of the raw EEG. The often-used sequential test strategy saves time, but the multiple testing increases the probability of falsely detected responses. Therefore, the critical test value must guarantee the specified error probability for the maximum test step number. However, response detection at all lower test step numbers is disadvantaged. We propose calculating the critical test values for each test step number, which correspond exactly to the given error probability. DESIGN: The critical test values for each test step were calculated by the method described by Sturzebecher et al (2005) . A table with the test values was implemented with customized software of the Eclipse ASSR system((r)) (Interacoustics, Denmark). STUDY SAMPLE: Table-related testing was performed on a sample of raw EEG data collected during the routine clinical measurement of frequency-specific auditory steady-state responses (ASSR) for hearing threshold assessment. RESULTS: The new test strategy leads to a significantly increased detection rate and a significantly shorter detection time. CONCLUSIONS: The new test strategy can improve the performance of the objective hearing threshold assessment and of the newborn hearing screening. PMID- 24219122 TI - Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: long-term patient survival and mechanism of function. AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Surgery remains the primary curative treatment but nearly 50% of patients relapse as consequence of micrometastatic or minimal residual disease (MRD) at the time of surgery. Spontaneous T-cell-mediated immune responses to CRC tumor-associated antigens (TAAs) in tumor-draining lymph nodes and in the bone marrow (BM) lead to infiltration of the tumors by lymphocytes. Certain types of such tumor-infiltrating lymphocytes (TILs) have a positive and others a negative impact on the patients' prognosis. This review focuses on advances in CRC active specific immunotherapy (ASI), in particular on results from randomized controlled clinical studies employing therapeutic autologous tumor cell vaccines. The observed improvement of long-term survival is explained by activation and mobilization of a pre-existing repertoire of tumor-reactive memory T cells which, according to recent discoveries, reside in distinct niches of patients' bone marrow in neighborhood with hematopoietic (HSC) and mesenchymal (MSC) stem cells. Interestingly, memory T cells also contain a subset of stem memory T cells (SMTs) in addition to effector (EMTs) and central memory T cells (CMTs). The mechanism of function of a therapeutic vaccine in a chronic disease is distinct from that of prophylactic vaccines which have to generate de novo protective immune responses. The advantage of autologous vaccines for mobilization of a broad and highly individual repertoire of memory T cells will be discussed. PMID- 24219123 TI - Prescribing patterns of glucosamine in an older population: a national cohort study. AB - BACKGROUND: Glucosamine is commonly prescribed as a disease modulating agent in osteoarthritis. However, the evidence to date suggests that it has a limited impact on the clinical symptoms of the disease including joint pain, radiological progression, function and quality of life. The aim of this study was to examine the prescribing patterns of glucosamine from 2002-2011 in an elderly Irish national population cohort using data from the Health Service Executive Primary Care Reimbursement (HSE-PCRS) General medical services (GMS) Scheme. METHODS: Patients aged >= 70 years on the HSE-PCRS pharmacy claims database between January 2002 and December 2011 were included. ATC code M01AX05 (glucosamine) was extracted. Prevalence rates per 1000 eligible population with 95% confidence intervals were calculated for all years and age groups (70-74 years, >=75 years). A negative binomial regression analysis was used to determine longitudinal usage trends and compare prevalence rates across years, sex and age groups. RESULTS: The annual patient rate of glucosamine prescribing increased significantly from 13.0/1000 eligible population (95% CI 12.6-13.4) in 2002 to 68.7/1000 population (95% CI 67.8-69.5) in 2009 before decreasing to 62.4/1000 population (95% CI 61.6 63.2) in 2011. The rate of prescribing of glucosamine varied with sex, with women receiving significantly more prescriptions than men. The cost of glucosamine also increased from 2002-2008. In 2008 total expenditure reached a high of ?4.6 million before decreasing to ?2.6 million in 2011. CONCLUSION: The national trend in prescribing of glucosamine increased significantly from 2002 to 2009 before decreasing in 2010 and 2011, in keeping with current international guidelines. There is a need for awareness among healthcare professionals and patients alike of the best available evidence to inform decision making relating to the prescription and consumption of such supplements. PMID- 24219124 TI - A Report on Bovine Ephemeral Fever Virus in Turkey: Antigenic Variations of Different Strains of EFV in the 1985 and 2012 Outbreaks Using Partial Glycoprotein Gene Sequences. AB - We described the aetiological agents of outbreaks of bovine ephemeral fever (BEF) that occurred in 1985 and 2012 in Turkey, and identify mutations in the viruses from both outbreaks. Outbreaks have emerged periodically every 4-5 years in the same regions in Turkey. Because these regions are located in a subtropical climatic zone, good conditions for vector populations exist. The results of this study show that the BEFVs from outbreaks in Turkey vary significantly. Effective prevention will require a vaccine that contains BEFVs from different genetic clusters. PMID- 24219125 TI - Juvenile-like (inflammatory/hyperplastic) mucosal polyps of the gastrointestinal tract in neurofibromatosis type 1. AB - AIMS: Diffuse neurofibromatosis/ganglioneuromatosis, solitary/plexiform neurofibroma, periampullary carcinoids and gastrointestinal stromal tumour (GIST) are the main gastrointestinal manifestations of neurofibromatosis type 1 (NF-1, von Recklinghausen disease). Inflammatory (juvenile-like) polyps have not been recognised to date as specific gastrointestinal (GI) manifestations of NF-1. METHODS AND RESULTS: We describe four males aged 23-65 years with NF-1 and inflammatory (juvenile-like) gastrointestinal polyps, and review the literature for similar cases. Two patients had single polyps (sigmoid colon and antrum, respectively), one had two polyps (left colon), and one had three polyps (distal oesophagus and colon). Histological appearances were variable, ranging from juvenile-like to granulation tissue-rich, predominantly inflammatory and hyperplastic. Three lesions showed obliterative vasculopathic changes. None had neurofibromatous or ganglioneuromatous polyps. A review of the literature disclosed 11 similar cases. Most patients presented with severe gastrointestinal symptoms and/or anaemia. CONCLUSIONS: NF-1-associated inflammatory polyps probably represent specific GI manifestations of this disorder, and should be considered, particularly in patients with GI symptoms. They should be distinguished from inflammatory fibroid polyps and from juvenile-like changes associated with ganglioneuroma/ganglioneuromatosis and neurofibroma/neurofibromatosis. Their aetiology remains obscure, but different mechanisms, including NF-1 inactivation, NF-1-associated vasculopathy, and localised mucosal prolapse/damage caused by motility disorders, might be involved. PMID- 24219126 TI - Is it better to be average? High and low performance as predictors of employee victimization. AB - Given increased interest in whether targets' behaviors at work are related to their victimization, we investigated employees' job performance level as a precipitating factor for being victimized by peers in one's work group. Drawing on rational choice theory and the victim precipitation model, we argue that perpetrators take into consideration the risks of aggressing against particular targets, such that high performers tend to experience covert forms of victimization from peers, whereas low performers tend to experience overt forms of victimization. We further contend that the motivation to punish performance deviants will be higher when performance differentials are salient, such that the effects of job performance on covert and overt victimization will be exacerbated by group performance polarization, yet mitigated when the target has high equity sensitivity (benevolence). Finally, we investigate whether victimization is associated with future performance impairments. Results from data collected at 3 time points from 576 individuals in 62 work groups largely support the proposed model. The findings suggest that job performance is a precipitating factor to covert victimization for high performers and overt victimization for low performers in the workplace with implications for subsequent performance. PMID- 24219128 TI - Mediating the contradiction of d33 and TC in potassium-sodium niobate lead-free piezoceramics. AB - For potassium-sodium niobate, the piezoelectric constant (d33) was usually improved by sacrificing the Curie temperature (TC). In this work, a material system of 0.992(K0.46Na0.54)0.965Li0.035Nb(1-x)Sb(x)O3-0.008BiScO3 has been designed and prepared with the aim of achieving both a large d33 and a high TC at the same time. The chemical compositions are found to be homogeneously distributed in the ceramics. The introduction of Sc is found to be responsible for different grain sizes. The rhombohedral-tetragonal phase coexistence zone lies in the composition range of 0.02= 1.8) enhanced the extent of bioreduction compared to pure Fh. The coprecipitated HA also altered the secondary Fe mineralization pathway by inhibiting goethite formation, reducing the amount of magnetite formation, and increasing the formation of a green rust-like phase. This study indicates that coprecipitated OM may influence the rates, pathway, and mineralogy of biogeochemical Fe cycling and anaerobic Fe respiration within soils. PMID- 24219168 TI - Centrifugal blood pump for temporary ventricular assist devices with low priming and ceramic bearings. AB - A new model of centrifugal blood pump for temporary ventricular assist devices has been developed and evaluated. The design of the device is based on centrifugal pumping principles and the usage of ceramic bearings, resulting in a pump with reduced priming (35 +/- 2 mL) that can be applied for up to 30 days. Computational fluid dynamic (CFD) analysis is an efficient tool to optimize flow path geometry, maximize hydraulic performance, and minimize shear stress, consequently decreasing hemolysis. Initial studies were conducted by analyzing flow behavior with different impellers, aiming to determine the best impeller design. After CFD studies, rapid prototyping technology was used for production of pump prototypes with three different impellers. In vitro experiments were performed with those prototypes, using a mock loop system composed of Tygon tubes, oxygenator, digital flow meter, pressure monitor, electronic driver, and adjustable clamp for flow control, filled with a solution (1/3 water, 1/3 glycerin, 1/3 alcohol) simulating blood viscosity and density. Flow-versus pressure curves were obtained for rotational speeds of 1000, 1500, 2000, 2500, and 3000 rpm. As the next step, the CFD analysis and hydrodynamic performance results will be compared with the results of flow visualization studies and hemolysis tests. PMID- 24219169 TI - Iron isotope characteristics of Hot Springs at Chocolate Pots, Yellowstone National Park. AB - Chocolate Pots Hot Springs in Yellowstone National Park is a hydrothermal system that contains high aqueous ferrous iron [~0.1 mM Fe(II)] at circumneutral pH conditions. This site provides an ideal field environment in which to test our understanding of Fe isotope fractionations derived from laboratory experiments. The Fe(III) oxides, mainly produced through Fe(II) oxidation by oxygen in the atmosphere, have high 56Fe/54Fe ratios compared with the aqueous Fe(II). However, the degree of fractionation is less than that expected in a closed system at isotopic equilibrium. We suggest two explanations for the observed Fe isotope compositions. One is that light Fe isotopes partition into a sorbed component and precipitate out on the Fe(III) oxide surfaces in the presence of silica. The other explanation is internal regeneration of isotopically heavy Fe(II) via dissimilatory Fe(III) reduction farther down the flow path as well as deeper within the mat materials. These findings provide evidence that silica plays an important role in governing Fe isotope fractionation factors between reduced and oxidized Fe. Under conditions of low ambient oxygen, such as may be found on early Earth or Mars, significantly larger Fe isotope variations are predicted, reflecting the more likely attainment of Fe isotope equilibrium associated with slower oxidation rates under low-O2 conditions. PMID- 24219171 TI - Rapid spread of Schmallenberg virus-infected biting midges (Culicoides spp.) across Denmark in 2012. AB - Detection of Schmallenberg virus RNA, using real-time RT-PCR, in biting midges (Culicoides spp.) caught at 48 locations in 2011 and four well-separated farms during 2012 in Denmark, revealed a remarkably rapid spread of virus-infected midges across the country. During 2012, some 213 pools of obsoletus group midges (10 specimens per pool) were examined, and of these, 35 of the 174 parous pools were Schmallenberg virus RNA positive and 11 of them were positive in the heads. Culicoides species-specific PCRs identified both C. obsoletus and C. dewulfi as vectors of Schmallenberg virus. PMID- 24219170 TI - Efficacy of robot-assisted radical cystectomy (RARC) in advanced bladder cancer: results from the International Radical Cystectomy Consortium (IRCC). AB - OBJECTIVE: To characterise the surgical feasibility and outcomes of robot assisted radical cystectomy (RARC) for pathological T4 bladder cancer. PATIENTS AND METHODS: Retrospective evaluation of a prospectively maintained International Radical Cystectomy Consortium database was conducted for 1118 patients who underwent RARC between 2003 and 2012. We dichotomised patients based on pathological stage (<=pT3 vs pT4) and evaluated demographic, operative and pathological variables in relation to morbidity and mortality. RESULTS: In all, 1000 <=pT3 and 118 pT4 patients were evaluated. The pT4 patients were older than the <=pT3 patients (P = 0.001). The median operating time and blood loss were 386 min and 350 mL vs 396 min and 350 mL for p T4 and <=pT3, respectively. The complication rate was similar (54% vs 58%; P = 0.64) among <=pT3 and pT4 patients, respectively. The overall 30- and 90-day mortality rate was 0.4% and 1.8% vs 4.2% and 8.5% for <=pT3 vs pT4 patients (P < 0.001), respectively. The body mass index (BMI), American Society of Anesthesiology score, length of hospital stay (LOS) >10 days, and 90-day readmission were significantly associated with complications in pT4 patients. Meanwhile, BMI, LOS >10 days, grade 3-5 complications, 90-day readmission, smoking, previous abdominal surgery and neoadjuvant chemotherapy were significantly associated with mortality in pT4 patients. On multivariate analysis, BMI was an independent predictor of complications in pT4 patients, but not for mortality. CONCLUSIONS: RARC for pT4 bladder cancer is surgically feasible but entails significant morbidity and mortality. BMI was independent predictor of complications in pT4 patients. PMID- 24219172 TI - Intention, emotion, and action: a neural theory based on semantic pointers. AB - We propose a unified theory of intentions as neural processes that integrate representations of states of affairs, actions, and emotional evaluation. We show how this theory provides answers to philosophical questions about the concept of intention, psychological questions about human behavior, computational questions about the relations between belief and action, and neuroscientific questions about how the brain produces actions. Our theory of intention ties together biologically plausible mechanisms for belief, planning, and motor control. The computational feasibility of these mechanisms is shown by a model that simulates psychologically important cases of intention. PMID- 24219173 TI - Molecular epidemiology of Campylobacter jejuni human and chicken isolates from two health units. AB - A study was conducted over a 2-year period in the Perth District and Wellington Dufferin-Guelph health units in Ontario, with an objective of using comparative genomic fingerprinting (CGF) with a 40-gene assay (CGF40) to investigate the association between human cases of campylobacteriosis and spatially and temporally related Campylobacter isolates from retail chicken. CGF results were available for isolates from 115 human cases and 718 retail chicken samples. These data were combined with CGF results from a large reference database of Campylobacter isolates. Isolates were categorized into types based on >90% CGF40 fingerprint similarity (CGF-90%). CGF-90% types were categorized as chicken associated (CA90) when the proportion of animal isolates in the given type that originated from chicken was at least 80% and was statistically significant. Risk factor data were collected from cases by questionnaire. Urban cases were significantly more likely than rural cases to be CA90 and there were significantly fewer CA90 cases in the second year of the study. Due to the population distribution in Canada and most industrialized countries, the majority of campylobacteriosis cases are urban dwellers. Therefore, the association between urban cases and chicken-associated types of Campylobacter emphasizes the importance of educational and food safety efforts to reduce the impact of Campylobacter from retail chicken on public health. Sources other than chicken may be more important for rural dwellers. PMID- 24219174 TI - Clozapine, a fast-off-D2 antipsychotic. AB - Ever since clozapine was first synthesized and tested, it showed the unique property of having antipsychotic action but no Parkinson-like motor side effects. The antipsychotic basis of clozapine is to transiently occupy dopamine D2 receptors in the human striatum, in contrast to haloperidol and chlorpromazine, which have a prolonged occupation of D2 receptors. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine's transient occupation of D2 receptors permits patients to move easily and comfortably. PMID- 24219175 TI - Temperature-dependent toxicities of nano zinc oxide to marine diatom, amphipod and fish in relation to its aggregation size and ion dissolution. AB - This study, for the first time, concurrently investigated the influence of seawater temperature, exposure concentration and time on the aggregation size and ion dissolution of nano zinc oxides (nZnO) in seawater, and the interacting effect of temperature and waterborne exposure of nZnO to the marine diatom Skeletonema costatum, amphipod Melita longidactyla and fish Oryzias melastigma, respectively. Our results showed that aggregate size was jointly affected by seawater temperature, nZnO concentration and exposure time. Among the three factors, the concentration of nZnO was the most important and followed by exposure time, whereas temperature was less important as reflected by their F values in the three-way analysis of variance (concentration: F3, 300 = 247.305; time: F2, 300 = 20.923 and temperature: F4, 300 = 4.107; All p values <0.001). The aggregate size generally increased with increasing nZnO concentration and exposure time. The release of Zn ions from nZnO was significantly influenced by seawater temperature and exposure time; the ion dissolution rate generally increased with decreasing temperature and increasing exposure time. Growth inhibition of diatoms increased with increasing temperature, while temperature and nZnO had an interactional effect on their photosynthesis. For the amphipod, mortality was positively correlated with temperature. Fish larvae growth rate was only affected by temperature but not nZnO, while the two factors interactively modulated the expression of heat shock and metallothionein proteins. Evidently, temperature can influence aggregate size and ion dissolution and thus toxicity of nZnO to the marine organisms in a species-specific manner. PMID- 24219176 TI - Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity. AB - Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 +/- 5.8 mg (1.2 +/- 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 +/- 0.2 mg/ml (29.0 +/- 3.0 MUg CE/ml), whereas IC50 for serum ACE was 0.6 +/- 0.1 mg/ml (11.0 +/- 1.2 MUg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. PMID- 24219177 TI - How is organ transplantation depicted in internal medicine and transplantation journals. AB - BACKGROUND: In their book Spare Parts, published in 1992, Fox and Swazey criticized various aspects of organ transplantation, including the routinization of the procedure, ignorance regarding its inherent uncertainties, and the ethos of transplant professionals. Using this work as a frame of reference, we analyzed articles on organ transplantation published in internal medicine and transplantation journals between 1995 and 2008 to see whether Fox and Swazey's critiques of organ transplantation were still relevant. METHODS: Using the PubMed database, we retrieved 1,120 articles from the top ten internal medicine journals and 4,644 articles from the two main transplantation journals (Transplantation and American Journal of Transplantation). Out of the internal medicine journal articles, we analyzed those in which organ transplantation was the main topic (349 articles). A total of 349 articles were randomly selected from the transplantation journals for content analysis. RESULTS: In our sample, organ transplantation was described in positive terms and was presented as a routine treatment. Few articles addressed ethical issues, patients' experiences and uncertainties related to organ transplantation. The internal medicine journals reported on more ethical issues than the transplantation journals. The most important ethical issues discussed were related to the justice principle: organ allocation, differential access to transplantation, and the organ shortage. CONCLUSION: Our study provides insight into representations of organ transplantation in the transplant and general medical communities, as reflected in medical journals. The various portrayals of organ transplantation in our sample of articles suggest that Fox and Swazey's critiques of the procedure are still relevant. PMID- 24219178 TI - Evaluation of glycodendron and synthetically modified dextran clearing agents for multistep targeting of radioisotopes for molecular imaging and radioimmunotherapy. AB - A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific antitumor antibody streptavidin fusion protein (scFv4-SA) in vivo, to improve tumor-to-normal tissue concentration ratios for multistep targeted (MST) radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with an average molecular weight of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogues (e.g., CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of (124)I-labeled-scFv4-SA clearance and dual-label biodistribution studies following MST directed at subcutaneous (s.c.) human colon adenocarcinoma xenografts in mice. The MST protocol consists of three injections: first, a scFv4 SA specific for an antitumor-associated glycoprotein (TAG-72); second, CA16 or other clearing agent; and third, radiolabeled biotin. We observed using PET imaging of the (124)I-labeled-scFv4-SA clearance that the spatial arrangement of ligands conjugated to NAG (i.e., biotin linked with an extended spacer, referred to herein as long-chain (LC)) can impact the binding to the antibody in circulation and subsequent liver uptake of the NAG-antibody complex. Also, NAGB CA32-LC or CA16-LC can be utilized during MST to achieve comparable tumor-to blood ratios and absolute tumor uptake seen previously with CA16. Finally, DEXB was equally effective as NAGB CA32-LC at lowering scFv4-SA in circulation, but at the expense of reducing absolute tumor uptake of radiolabeled biotin. PMID- 24219179 TI - Psychotherapy credibility ratings: patient predictors of credibility and the relation of credibility to therapy outcome. AB - OBJECTIVE: The current investigation examined the relation between credibility ratings for adult psychotherapies and a variety of patient factors as well as the relation between credibility ratings and subsequent symptom change. METHOD: A pooled study database that included studies evaluating the efficacy of cognitive and psychodynamic therapies for a variety of disorders was used. For all studies, a three-item credibility scale was administered at session 2. Patient variables at baseline were used to predict early treatment credibility. RESULTS: Early symptom improvement, age, education, and expectation of improvement were all significantly predictive of credibility scores at session 2. In one combined multiple regression model controlling for treatment, study, and early symptom change, age, education, and expectation of improvement remained significantly predictive of credibility scores. Credibility was predictive of subsequent symptom change even when controlling for age, education, expectation of improvement, and early symptom improvement. CONCLUSIONS: These findings suggest that age and education, in addition to expectations of improvement and the amount of early symptom improvement, may influence the patient's perceptions of the credibility of a treatment rationale early in the treatment process and that credibility ratings predict subsequent symptom change. PMID- 24219180 TI - Warmer temperatures increase disease transmission and outbreak intensity in a host-pathogen system. AB - While rising global temperatures are increasingly affecting both species and their biotic interactions, the debate about whether global warming will increase or decrease disease transmission between individuals remains far from resolved. This may stem from the lack of empirical data. Using a tractable and easily manipulated insect host-pathogen system, we conducted a series of field and laboratory experiments to examine how increased temperatures affect disease transmission using the crop-defoliating pest, the fall armyworm (Spodoptera frugiperda) and its species-specific baculovirus, which causes a fatal infection. To examine the effects of temperature on disease transmission in the field, we manipulated baculovirus density and temperature. As infection occurs when a host consumes leaf tissue on which the pathogen resides, baculovirus density was controlled by placing varying numbers of infected neonate larvae on experimental plants. Temperature was manipulated by using open-top chambers (OTCs). The laboratory experiments examined how increased temperatures affect fall armyworm feeding and development rates, which provide insight into how host feeding behaviour and physiology may affect transmission. Disease transmission and outbreak intensity, measured as the cumulative fraction infected during an epizootic, increased at higher temperatures. However, there was no appreciable change in the mean transmission rate of the disease, which is often the focus of empirical and theoretical research. Instead, the coefficient of variation (CV) associated with the transmission rate shrunk. As the CV decreased, heterogeneity in disease risk across individuals declined, which resulted in an increase in outbreak intensity. In the laboratory, increased temperatures increased feeding rates and decreased developmental times. As the host consumes the virus along with the leaf tissue on which it resides, increased feeding rate is likely to increase the probability of an individual consuming virus-infected leaf tissue. On the other hand, decreased developmental time increases the sloughing of midgut cells, which is predicted to hinder viral infection. Increases in outbreak intensity or epizootic severity, as the climate warms, may lead to changes in the long-term dynamics of pests whose populations are strongly affected by host pathogen interactions. Overall, this work demonstrates that the usual assumptions governing these effects, via changes in the mean transmission rate alone, may not be correct. PMID- 24219181 TI - Structural characterization of native autoinducing peptides and abiotic analogues reveals key features essential for activation and inhibition of an AgrC quorum sensing receptor in Staphylococcus aureus. AB - Staphylococcus aureus is a major human pathogen that uses quorum sensing (QS) to control virulence. Its QS system is regulated by macrocyclic peptide signals (or autoinducing peptides (AIPs)) and their cognate transmembrane receptors (AgrCs). Four different specificity groups of S. aureus have been identified to date (groups I-IV), each of which uses a different AIP:AgrC pair. Non-native ligands capable of intercepting AIP:AgrC binding, and thereby QS, in S. aureus have attracted considerable interest as chemical tools to study QS pathways and as possible antivirulence strategies for the treatment of infection. We recently reported a set of analogues of the group-III AIP that are capable of strongly modulating the activity of all four AgrC receptors. Critical to the further development of such ligands is a detailed understanding of the structural features of both native AIPs and non-native analogues that are essential for activity. Herein, we report the first three-dimensional structural analysis of the known native AIP signals (AIPs-I-IV) and several AIP-III analogues with varied biological activities using NMR spectroscopy. Integration of these NMR studies with the known agonism and antagonism profiles of these peptides in AgrC III revealed two key structural elements that control AIP-III (and non-native peptide) activity: (1) a tri-residue hydrophobic "knob" essential for both activation and inhibition and (2) a fourth anchor point on the exocyclic tail needed for receptor activation. These results provide strong structural support for a mechanism of AIP-mediated AgrC activation and inhibition in S. aureus , and should facilitate the design of new AgrC ligands with enhanced activities (as agonists or antagonists) and simplified chemical structures. PMID- 24219182 TI - Ecological momentary assessment of stressful events and negative affect in bulimia nervosa. AB - OBJECTIVE: Negative affect precedes binge eating and purging in bulimia nervosa (BN), but little is known about factors that precipitate negative affect in relation to these behaviors. We aimed to assess the temporal relation among stressful events, negative affect, and bulimic events in the natural environment using ecological momentary assessment. METHOD: A total of 133 women with current BN recorded their mood, eating behavior, and the occurrence of stressful events every day for 2 weeks. Multilevel structural equation mediation models evaluated the relations among Time 1 stress measures (i.e., interpersonal stressors, work/environment stressors, general daily hassles, and stress appraisal), Time 2 negative affect, and Time 2 binge eating and purging, controlling for Time 1 negative affect. RESULTS: Increases in negative affect from Time 1 to Time 2 significantly mediated the relations between Time 1 interpersonal stressors, work/environment stressors, general daily hassles, and stress appraisal and Time 2 binge eating and purging. When modeled simultaneously, confidence intervals for interpersonal stressors, general daily hassles, and stress appraisal did not overlap, suggesting that each had a distinct impact on negative affect in relation to binge eating and purging. CONCLUSIONS: Our findings indicate that stress precedes the occurrence of bulimic behaviors and that increases in negative affect following stressful events mediate this relation. Results suggest that stress and subsequent negative affect may function as maintenance factors for bulimic behaviors and should be targeted in treatment. PMID- 24219184 TI - Metabolism of nonesterified and esterified hydroxycinnamic acids in red wines by Brettanomyces bruxellensis. AB - While Brettanomyces can metabolize nonesterified hydroxycinnamic acids found in grape musts/wines (caffeic, p-coumaric, and ferulic acids), it was not known whether this yeast could utilize the corresponding tartaric acid esters (caftaric, p-coutaric, and fertaric acids, respectively). Red wines from Washington and Oregon were inoculated with B. bruxellensis, while hydroxycinnamic acids were monitored by HPLC. Besides consuming p-coumaric and ferulic acids, strains I1a, B1b, and E1 isolated from Washington wines metabolized 40-50% of caffeic acid, a finding in contrast to strains obtained from California wines. Higher molar recoveries of 4-ethylphenol and 4-ethylguaiacol synthesized from p coumaric and ferulic acids, respectively, were observed in Washington Cabernet Sauvignon and Syrah but not Merlot. This finding suggested that Brettanomyces either (a) utilized vinylphenols formed during processing of some wines or (b) metabolized other unidentified phenolic precursors. None of the strains of Brettanomyces studied metabolized caftaric or p-coutaric acids present in wines from Washington or Oregon. PMID- 24219183 TI - Anhedonia, depressed mood, and smoking cessation outcome. AB - OBJECTIVE: Although the relation between lifetime depression and smoking cessation outcome has been well studied, the proposition that different symptomatic expressions of depression exert disparate predictive effects on risk of smoking cessation failure has largely gone uninvestigated. This study analyzed the individual contributions of depression's 2 hallmark affective symptoms, anhedonia (i.e., diminished interest in normally enjoyable activities) and depressed mood (i.e., elevated sadness), to the prediction of smoking cessation outcome. METHOD: Participants were adult daily smokers (N = 1,469; mean age = 45 years, 58% female, 84% White) enrolled in a smoking cessation treatment study. Lifetime history of anhedonia and depressed mood were classified via structured interview prior to quit day. Seven-day point prevalence smoking abstinence was assessed at 8 weeks and 6 months postquit. RESULTS: When examined separately, both lifetime anhedonia, OR (95% CI) = 1.42 (1.16, 1.73), p = .004, and depressed mood, OR (95% CI) = 1.35 (1.11, 1.63), p = .002, predicted increased odds of relapse. These relations remained after adjusting for covariates, including lifetime depressive disorder, which did not predict outcome. After controlling for the covariation between lifetime anhedonia and depressed mood, anhedonia predicted cessation outcome, OR (95% CI) = 1.31 (1.05, 1.62), p = .02, while depressed mood did not (p = .19). Symptom duration (>2 weeks), treatment, and substance use disorder did not modify relations of lifetime anhedonia and depressed mood with cessation outcome. CONCLUSIONS: Results suggest that (1) symptoms of affective disturbance capture depression-relevant risk of cessation failure, which is not adequately demarcated by the lifetime depressive disorder diagnosis, and (2) anhedonia is a more sensitive index of this affective disturbance than depressed mood per se. Clinical attention to anhedonia may facilitate smoking cessation. PMID- 24219185 TI - Delayed diagnosis and associated factors among new pulmonary tuberculosis patients diagnosed at the emergency department of a tertiary care hospital in Porto Alegre, South Brazil: a prospective patient recruitment study. AB - BACKGROUND: Control of tuberculosis (TB) depends on early diagnosis and treatment at the primary health care level. However, many patients are still diagnosed late with TB at hospitals. The present study aimed to investigate the delay in diagnosis of TB patients at the emergency department. METHODS: This was a prospective study in a general, tertiary care, university-affiliated hospital of a city with a high prevalence of TB in Brazil. New TB patients >= 14 years diagnosed with pulmonary TB at the emergency department of Hospital de Clinicas de Porto Alegre were prospectively recruited between February 2010 and January 2012. The consenting patients meeting our inclusion criteria were interviewed using a pre-tested questionnaire. We evaluated the delay in time until diagnosis and identified factors associated with delayed diagnosis (patient and health care system delays). RESULTS: We included 153 patients. The median total time of delay, patient delay, and health care system delay were 60 (interquartile range [IQR]: 30-90.5 days), 30 (lQR: 7-60 days), and 18 (IQR: 9-39.5 days) days, respectively. The factors that were independently associated with patient delay (time >= 30 days) were crack (odds ratio [OR] = 4.88, p = 0.043) and cocaine (OR = 6.68, p = 0.011) use. The factors that were independently associated with health care system delay (time >= 18 days) were weight loss (OR = 2.76, p = 0.025), miliary pattern (OR = 5.33, p = 0.032), and fibrotic changes (OR = 0.12, p = 0.013) on chest X-ray. CONCLUSIONS: Patient delay appears to be the main problem in this city with a high prevalence of TB in Brazil. The main factor associated with patient delay is drug abuse (crack and cocaine). Our study shows substance abuse programs need to be aware of control of TB, with health interventions focusing on TB education programs. PMID- 24219186 TI - Quality of osteoporosis care of older Medicare recipients with fragility fractures: 2006 to 2010. AB - OBJECTIVES: To assess uptake of postfracture care guidelines in community dwelling Medicare recipients with fractures. DESIGN: Retrospective observational cohort study. SETTING: Claims-based study using U.S. Medicare administrative inpatient, outpatient (2003-2010), and prescription (2006-2010) data. PARTICIPANTS: Individuals aged 68 and older who survived at least 12 months after a fracture of the hip, radius, or humerus. MEASUREMENTS: Poisson regression modeled factors, including participant characteristics, comorbidities and hospital referral region (HRR), associated with bone density testing or osteoporosis pharmacotherapy in the 6 months after fracture. Models were repeated for participants with no osteoporosis care observed before fracture (attention naive). RESULTS: In 61,832 individuals with fractures, mean age was 80.6, 87.0% were female, 88.5% were white, 2.6% were black, and 62.1% were attention naive at the time of fracture; 21.8% received testing, pharmacotherapy, or both in the 6 months after fracture. In adjusted models, factors associated with significantly lower likelihood of receiving this care were black race, male sex, and an upper extremity fracture (vs hip). In models restricted to attention-naive participants, the same factors were associated with lower relative risk of receiving care. Adjusted HRR-level care rates ranged from 14.7% to 22.9% (10th to 90th percentile). The proportion receiving care increased from 2006 to 2009. CONCLUSION: Postfracture osteoporosis care was uncommon, particularly in black and male participants. Care increased over time, but for most, a fracture was insufficient to trigger effective secondary prevention, especially for participants who were not receiving prefracture osteoporosis attention. Clinicians and policy-makers must consider effective remedies to this persistent care gap. PMID- 24219187 TI - Biomarker-calibrated protein intake and physical function in the Women's Health Initiative. AB - OBJECTIVES: To determine whether preservation of physical function with aging may be partially met through modification in dietary protein intake. DESIGN: Prospective cohort study. SETTING: Women's Health Initiative (WHI) Clinical Trials (CT) and Observational Study (OS) conducted at 40 clinical centers. PARTICIPANTS: Women aged 50 to 79 (N = 134,961) with dietary data and one or more physical function measures. MEASUREMENTS: Physical function was assessed using the short-form RAND-36 at baseline and annually beginning in 2005 for all WHI participants and at closeout for CT participants (average ~7 years after baseline). In a subset of 5,346 participants, physical performance measures (grip strength, number of chair stands in 15 seconds, and timed 6-m walk) were assessed at baseline and Years 1, 3, and 6. Calibrated energy and protein intake were derived from regression equations using baseline food frequency questionnaire data collected on the entire cohort and doubly labeled water and 24-hour urinary nitrogen collected from a representative sample as reference measures. Associations between calibrated protein intake and each of the physical function measures were assessed using generalized estimating equations. RESULTS: Calibrated protein intake ranged from 6.6% to 22.3% energy. Higher calibrated protein intake at baseline was associated with higher self-reported physical function (quintile (Q)5, 85.6, 95% confidence interval (CI) = 81.9-87.5; Q1, 75.4, 95% CI = 73.2-78.5, P trend = .002) and a slower rate of functional decline (annualized change: Q5, -0.47, 95% CI = -0.63 to -0.39; Q1, -0.98, 95% CI = -1.18 to -0.75, P trend = .02). Women with higher calibrated protein intake also had greater grip strength at baseline (Q5, 24.7 kg, 95% CI = 24.3-25.2 kg; Q1, 24.1 kg, 95% CI = 23.6-24.5 kg, P trend = .04) and slower declines in grip strength (annualized change: Q5, -0.45 kg, 95% CI = -0.39 to -0.63 kg; Q1, -0.59 kg, 95% CI = -0.50 to -0.66 kg, P trend = .03). Women with higher calibrated protein intake also completed more chair stands at baseline (Q5, 7.11, 95% CI = 6.91 7.26; Q1, 6.61, 95% CI = 6.46-6.76, P trend = .002). CONCLUSION: Higher calibrated protein intake is associated with better physical function and performance and slower rates of decline in postmenopausal women. PMID- 24219188 TI - Changes in physical performance in older women according to presence and treatment of diabetes mellitus. AB - OBJECTIVES: To determine whether older women with diabetes mellitus have a greater longitudinal decline in physical performance than those without and whether any decline differs according to insulin sensitizer use. DESIGN: Prospective cohort study. SETTING: Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela, Pennsylvania. PARTICIPANTS: Community dwelling women (mean age 78.5 +/- 3.6) enrolled in the Study of Osteoporotic Fractures in 1997-98 and restudied 4.9 +/- 0.6 years later (N = 2,864). MEASUREMENTS: Women were categorized as having no diabetes mellitus (n = 2,680) or having diabetes mellitus (n = 184). A prescription medication inventory was used to determine use of insulin sensitizers (metformin and thiazolidinedione). The outcomes were longitudinal changes in physical performance measures, including grip strength, usual walk speed, and rapid walk speed. RESULTS: Estimates from fully adjusted models showed that women with diabetes mellitus had greater declines in usual walk speed (-0.16 m/s, 95% confidence interval (CI) = 0.19 to -0.14) and rapid walk speed (-0.21 m/s, 95% CI = -0.24 to -0.17) than those without (usual walk speed -0.11 m/s, 95% CI = -0.12 to -0.11, P < .001; rapid walk speed -0.15 m/s, 95% CI = -0.16 to -0.14; P = .005). Women with diabetes mellitus taking insulin sensitizers had less decline in usual walk speed than those not taking insulin sensitizers (P < .001). Declines in grip strength did not differ significantly by diabetes mellitus status or insulin sensitizer use. CONCLUSION: Older women with diabetes mellitus have a greater decline in walk speed, but not grip strength, than older women without diabetes mellitus. Clinical studies in older adults to determine whether diabetes mellitus treatments such as insulin sensitizers can prevent loss in walk speed and mobility are needed. PMID- 24219190 TI - Objectively measured physical activity and progressive loss of lean tissue in older Japanese adults: longitudinal data from the Nakanojo study. AB - OBJECTIVES: To relate 5-year lean tissue loss to habitual physical activity of elderly adults. DESIGN: Longitudinal. SETTING: Community of Nakanojo. PARTICIPANTS: Community-living Japanese aged 65 to 84 (200 men, 268 women). MEASUREMENTS: Daily 24-hour pedometer/accelerometer data, collected continuously for 5 years, were categorized into activity quartiles. Bioelectrical impedance measurements of lean body mass were taken annually. A sarcopenia threshold was defined arbitrarily as an appendicular lean mass/height(2) of more than 1 standard deviation below the mean for healthy young Japanese. RESULTS: Subjects with greater habitual physical activity retained a greater lean mass over the 5 years of observation. Controlling for baseline lean mass and age, final lean mass was greater for the third activity quartile (men and women with respective mean counts of 7,800 and 7,700 steps per day or mean duration of exercise at >3 metabolic equivalents (METs) of 20 and 17 minutes per day) than for the first and second quartiles. A multivariate-adjusted proportional hazards model predicted that, over the 5 years, men and women in the two lowest activity quartiles (<6,700 and <6,800 steps per day) were 2.3 (95% confidence interval (CI) = 1.4 4.5) and 3.0 (95% CI = 1.9-3.4) times as likely, respectively, to be sarcopenic as those in the highest activity quartile (>9,000 and >8,400 steps per day). Likewise, men and women with less than 16 and less than 14 minutes per day, respectively, of activity of more than 3 METs were 3.0 (95% CI = 2.0-6.0) and 3.5 (95% CI = 2.1-6.3) times as likely to develop sarcopenia as those with more than 28 and more than 22 minutes per day. CONCLUSION: After adjustment for potential confounders, the risk of developing sarcopenia was substantially lower in elderly people taking at least 7,000 to 8,000 steps per day or exercising for at least 15 to 20 minutes per day at an intensity greater than 3 METs. Clinicians should encourage seniors to get at least this volume of regular daily exercise. PMID- 24219189 TI - Motor learning versus standard walking exercise in older adults with subclinical gait dysfunction: a randomized clinical trial. AB - OBJECTIVES: To compare the effect of motor learning with that of standard exercise on measures of mobility and perceived function and disability. DESIGN: Single-blind randomized trial. SETTING: University research center. PARTICIPANTS: Older adults (n = 40) with a mean age of 77.1 +/- 6.0, normal walking speed (>= 1.0 m/s), and impaired motor skills (Figure of 8 walk time >8 seconds). INTERVENTIONS: The motor learning program incorporated goal-oriented stepping and walking to promote timing and coordination within the phases of the gait cycle. The standard program employed endurance training by treadmill walking. Both included strength training and were offered twice weekly for 1 hour for 12 weeks. MEASUREMENTS: Primary outcomes were mobility performance (gait efficiency, motor skill in walking, gait speed, walking endurance); secondary outcomes were perceived function and disability (Late-Life Function and Disability Instrument). RESULTS: Thirty-eight of 40 participants completed the trial (motor learning, n = 18; standard, n = 20). The motor learning group improved more than the standard group in gait speed (0.13 vs 0.05 m/s, P = .008) and motor skill (-2.2 vs -0.89 seconds, P < .001). Both groups improved in walking endurance (28.3 and 22.9 m, P = .14). Changes in gait efficiency and perceived function and disability were not different between the groups (P > .10). CONCLUSION: In older adults with subclinical gait dysfunction, motor learning exercise improved some parameters of mobility performance more than standard exercise. PMID- 24219191 TI - Hospitalizations of nursing home residents in the last year of life: nursing home characteristics and variation in potentially avoidable hospitalizations. AB - OBJECTIVES: To examine the incidence of, variations in, and costs of potentially avoidable hospitalizations (PAHs) of nursing home (NH) residents at the end of life and to identify the association between NH characteristics and a facility level quality measure (QM) for PAH. DESIGN: Retrospective. SETTING: Hospitalizations originating from NHs. PARTICIPANTS: Long-term care NH residents who died in 2007. MEASUREMENTS: A risk-adjusted QM was constructed for PAH. A Poisson regression model was used to predict the count of PAH given residents' risk factors. For each facility, the QM was defined as the difference between the observed facility-specific rate (per 1,000 person-years) of PAH (O) and the expected risk-adjusted rate (E). A logistic regression model with state fixed effects was then fit to examine the association between facility characteristics and the likelihood of having higher-than-expected rates of PAH (O-E > 0). QM values greater than 0 indicate worse-than-average quality. RESULTS: Almost 50% of hospital admissions for NH residents in their last year of life were for potentially avoidable conditions, costing Medicare $1 billion. Five conditions were responsible for more than 80% of PAHs. PAH QM across facilities showed significant variation (mean 12.0 +/- 142.3 per 1,000 person-years, range -399.48 to 398.09 per 1,000 person-years). Chain and hospital-based facilities were more likely to exhibit better performance (O-E < 0). Facilities with higher nursing staffing were more likely to have better performance, as were facilities with higher skilled staff ratio, those with nurse practitioners or physician assistants, and those with on-site X-ray services. CONCLUSION: Variations in facility-level PAHs suggest that a potential for reducing hospital admissions for these conditions may exist. Presence of modifiable facility characteristics associated with PAH performance could help us formulate interventions and policies for reducing PAHs at the end of life. PMID- 24219192 TI - Activity of daily living trajectories surrounding acute hospitalization of long stay nursing home residents. AB - OBJECTIVES: To explore patterns of change in nursing home (NH) residents' activities of daily living (ADLs), particularly surrounding acute hospital stays. DESIGN: Longitudinal study using Medicare and Minimum Data Set (MDS) assessments. SETTING: National sample of long-stay NH residents. PARTICIPANTS: NH residents who were hospitalized for the seven most-common inpatient diagnoses (N = 40,128). Each hospital admission was at least 90 days after any prior hospitalization and had at least two preceding MDS assessments. MEASUREMENTS: The MDS ADL long-form score, a simple sum of seven self-care variables coded from 0 (independent) to 4 (totally dependent) was used to indicate resident ADL function. Scores ranged from 0 to 28, with higher scores indicating greater impairment. A linear mixed model describing ADL trajectories was jointly estimated with time-to-event models for mortality and hospital readmission. RESULTS: Before hospitalization, the most common trajectory was stable (53.7%), with 27.5% of residents worsening and 18.8% improving. ADL function after hospital discharge was most often characterized as stable (43.1%) or worsening (39.2%). Mortality (20.3%) was higher for those with worsening prehospital ADL function (28.9%) than for those with stable (19.1%) or improving (11.3%) trajectories. Hospital diagnosis was associated with amount of ADL worsening and rate of subsequent ADL change. Most residents with the best initial function continued to worsen after hospital discharge. Cognitive impairment was associated with poorer ADL function and accelerated worsening of ADLs. CONCLUSION: For many long-stay NH residents, substantial and sustained ADL worsening accompanies acute hospitalization, so acute hospitalization presents an opportunity to revisit care goals; the results of the current study can help inform decision-making. PMID- 24219193 TI - Benefits of multimodal exercise intervention for postural control and frontal cognitive functions in individuals with Alzheimer's disease: a controlled trial. AB - OBJECTIVE: To verify the effects of a systematized multimodal exercise intervention program on frontal cognitive function, postural control, and functional capacity components of individuals with Alzheimer's disease (AD). DESIGN: Nonrandomized controlled trial with pre- and posttraining tests in a training group and a control group. SETTING: Kinesiotherapy program for seniors with AD, Sao Paulo State University. PARTICIPANTS: Convenience sample of older adults with AD (n = 30) were assigned to a training (n = 14; aged 78.6 +/- 7.1) and a control (n = 16; aged 77.0 +/- 6.3) group. INTERVENTION: The intervention program was structured with the aim of simultaneously promoting better balance and frontal cognitive capacity. The participants attended a 1-hour session three times a week for 16 weeks, whereas the control group did not participate in any activity during the same period. MEASUREMENTS: Frontal cognitive function was evaluated using the Montreal Cognitive Assessment, the Clock Drawing Test, the Frontal Assessment Battery, and the Symbol Search Subtest. Postural control (center of pressure area) was analyzed under four dual-task conditions. Functional capacity components were analyzed using the Timed Up and Go Test, the 30-second sit-to-stand test, the sit-and-reach test, and the Berg Functional Balance Scale. RESULTS: Intervention group participants showed a significant increase in frontal cognitive function (P < .001, partial eta(2) = 0.838), with less body sway (P = .04, partial eta(2) = 0.04) during the dual tasks, and greater functional capacity (P = .001, partial eta(2) = 0.676) after the 16-week period. CONCLUSION: Intervention participants performed better on dual-task activities and had better postural balance and greater functional capacity than controls. PMID- 24219194 TI - Objectively measured physical activity is related to cognitive function in older adults. AB - OBJECTIVES: To explore the relationship between cognitive functioning and time spent at different intensities of physical activity (PA) in free-living older adults. DESIGN: Cross sectional analyses. SETTING: Continuing care retirement communities. PARTICIPANTS: Older adults residing in seven continuing care retirement communities in San Diego County with an average age of 83; 70% were female, and 35% had a graduate-level education (N = 217). MEASUREMENTS: PA was measured objectively using hip worn accelerometers with data aggregated to the minute level. Three cut points were used to assess low light-intensity PA (LLPA), high light-intensity PA (HLPA), and moderate- to vigorous-intensity PA (MVPA). The Trail Making Test (TMT) Parts A and B were completed, and time for each test (seconds) and time for Part B minus time for Part A (seconds) were used as measures of cognitive function. Variables were log-transformed and entered into linear regression models adjusting for demographic factors (age, education, sex) and other PA intensity variables. RESULTS: LLPA was not related to any TMT test score. HLPA was significantly related to TMT A, B, and B minus A but only in unadjusted models. MVPA was related to TMT B and B minus A after adjusting for demographic variables. CONCLUSION: There may be a dose response between PA intensity and cognitive functioning in older adults. The stronger findings supporting a relationship between MVPA and cognitive functioning are consistent with previous observational and intervention studies. PMID- 24219195 TI - In-hospital mortality and coronary procedure use for individuals with dementia with acute myocardial infarction in the United States. AB - OBJECTIVES: To determine in-hospital mortality differences in individuals with dementia and acute myocardial infarction (AMI) when using invasive coronary procedures. DESIGN: Retrospective cohort study. SETTING: 2009 Nationwide Inpatient Sample. PARTICIPANTS: Individuals admitted with a primary diagnosis of AMI (N = 631,734) to 1,045 hospitals in 44 states during 2009. MEASUREMENTS: Dementia status and procedural use of diagnostic catheterization, percutaneous intervention (PCI), and coronary artery bypass grafts (CABG) as indicated by International Classification of Diseases, Ninth Revision, codes. The primary outcome was in-hospital mortality. Using multivariable analysis adjusted for covariates, associations were made between coronary procedural use in individuals with dementia and in-hospital mortality. Additional multivariable analysis identified the association between utilization of coronary procedures and in hospital mortality in AMI patients with dementia. RESULTS: Dementia diagnosis (n = 15,335) was associated with greater likelihood of in-hospital mortality (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.15-1.29, P < .001) and less use of diagnostic catheterization (OR = 0.37, 95% CI = 0.35-0.40, P < .001), PCI (OR = 0.37, 95% CI = 0.35-0.40, P < .001), and CABG (OR = 0.19, 95% CI = 0.16 0.22, P < .001). There was less likelihood of in-hospital mortality in participants with dementia who received diagnostic catheterization (OR = 0.36, 95% CI = 0.16-0.78, P < .001), PCI (OR = 0.57, 95% CI = 0.47-0.70, P < .001), or CABG (OR = 0.22, 95% CI = 0.08-0.56, P < .001) than in those not receiving respective interventions. CONCLUSION: Dementia is a significant predictor of in hospital mortality for hospitalized individuals with AMI and is associated with less use of invasive coronary procedures. Beyond differing care patterns for individuals with AMI and dementia, these results indicate that individuals with dementia are at substantially greater risk for in-hospital mortality when they do not receive procedural interventions. PMID- 24219196 TI - Interaction between cognitive impairment and discharge destination and its effect on rehospitalization. AB - OBJECTIVES: To evaluate the effect of cognitive impairment on rehospitalization in older adults. DESIGN: One-year longitudinal study. SETTING: Medical service of an urban, 340-bed public hospital in Indianapolis between July 2006 and March 2008. PARTICIPANTS: Individuals aged 65 and older admitted to the medical service (N = 976). MEASUREMENTS: Rehospitalization was defined as any hospital admission after the index admission. Participant demographics, discharge destination, Charlson Comorbidity Index, Acute Physiology Score, and prior hospitalizations were measured as the confounders. Participants were considered to have cognitive impairment if they had two or more errors on the Short Portable Mental Status Questionnaire. RESULTS: After adjusting for confounders, a significant interaction between cognitive impairment and discharge location was found to predict rehospitalization rate (P = .008) and time to 1-year rehospitalization (P = .03). Participants with cognitive impairment discharged to a facility had a longer time to rehospitalization (median 142 days) than participants with no cognitive impairment (median 98 days) (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.58-1.02, P = .07), whereas participants with cognitive impairment discharged to home had a slightly shorter time to rehospitalization (median 182 days) than those without cognitive impairment (median 224 days) (HR = 1.15, 95% CI = 0.92-1.43, P = .23). These two nonsignificant HRs in opposite directions were significantly different from each other (P = .03). CONCLUSION: Discharge destination modifies the association between cognitive impairment and rehospitalization. Of participants discharged to a facility, those without cognitive impairment had higher rehospitalization rates, whereas the rates were similar between cognitively impaired and intact participants discharged to the community. PMID- 24219197 TI - High-intensity progressive resistance training improves flat-ground walking in older adults with symptomatic peripheral arterial disease. AB - OBJECTIVES: To assess the efficacy of whole-body progressive resistance training (PRT) as a treatment for the symptoms of peripheral arterial disease (PAD) in older adults. DESIGN: Randomized controlled pilot trial. SETTING: University clinical weight training facility in Sydney, Australia. PARTICIPANTS: Twenty-two older adults with symptomatic PAD. INTERVENTIONS: The efficacy of supervised whole-body high-intensity PRT (H-PRT) with low-intensity nonprogressive resistance training (L-RT) and a usual care control group that performed unsupervised walking for 6 months was compared. MEASUREMENTS: Pilot outcome measures included 6-minute walk (6 MW) outcomes, body composition, dynamic muscle strength and endurance, and performance-based tests of function. RESULTS: Mean age was 71.1 +/- 7.2. Mean ankle brachial index was 0.55 +/- 0.13. Exercise adherence was similar in all groups (P = .29). H-PRT (n = 8) improved total 6MW distance (mean difference (MD) 62.6 +/- 58.0 m, P = .02) significantly more than L-RT (n = 7; MD=-48.2 +/- 67.6 m) and controls (n = 7; MD=-9.9 +/- 52.9 m). Change in 6MW onset of claudication was significantly and independently related to change in bilateral calf endurance (correlation coefficient (r) = 0.65, P = .03), and change in 6MW distance was significantly and independently related to change in bilateral hip extensor endurance (r = 0.71, P = .02) in all groups. CONCLUSION: H-PRT significantly improved 6MW ability in older adults with intermittent claudication from PAD, whereas L-RT and unsupervised walking did not. Improvement in walking ability was significantly related to improvements in bilateral calf and hip extensor endurance, supporting further investigations targeted at musculoskeletal impairment in this cohort. PMID- 24219198 TI - Innovative care delivery model to address obesity in older African-American women: Senior Wellness Initiative and Take Off Pounds Sensibly collaboration for health (SWITCH). AB - OBJECTIVES: To determine the feasibility and acceptability of integrating Take Off Pounds Sensibly (TOPS), a national nonprofit weight-loss program through which people have lost a clinically significant amount of weight, into a community program that serves African Americans (AAs) and to determine weight change. DESIGN: Single-group pilot design. SETTING: Denver, Colorado. PARTICIPANTS: Community-dwelling participants aged 51 to 85. INTERVENTION: Participants were recruited through a program that serves AAs, and new TOPS chapters were started at a church, senior center, and senior residence for independent living. MEASUREMENTS: Feasibility was measured by determining the ease of recruitment and acceptability was measured according to retention. The secondary outcome was weight change. RESULTS: Sixty-four percent of people who were referred to the program or attended an information session participated in the study. The retention rate at 52 weeks was 79%. At 52 weeks, 16 of 48 participants had lost 5% or more of their initial weight, and 23 had lost 0% to 4.9% of their initial weight. CONCLUSIONS: Recruiting AA women through the Center for African American Health was feasible, and the program was acceptable. One third of participants lost a clinically significant amount of weight. TOPS may be one way to combat the health disparity of obesity in AA women. PMID- 24219199 TI - "You're being paged!" outcomes of a nursing home on-call role-playing and longitudinal curriculum. AB - Effectively handling telephone calls about nursing home (NH) residents is an important skill for healthcare professionals, but little formal training is typically provided. The objective of the current study was to describe and evaluate the effectiveness of a novel structured role-playing didactic session followed by an on-call NH longitudinal clinical experience. The effectiveness of the structured role-playing didactic session was compared in different learners, including geriatric medicine fellows (n = 10), family medicine residents and faculty (n = 14), nurse practitioner students (n = 31), and other learners (n = 7). The curriculum focused on common problems encountered while caring for NH residents during on-call periods. Learners rated themselves using an 18-item pre/post questionnaire including five attitude and 13 skills questions, using a 1 to-5 Likert scale. T-tests were used to compare means before and after sessions. Significant improvements were found in overall mean attitudes and skills scores. For all learners, the greatest improvements were seen in "comfort in managing residents at the NH," "managing feeding or gastrostomy tube dislodgement," "identifying different availability of medications, laboratory studies, and procedures in NH," and "describing steps to send NH residents to the emergency department." Geriatric medicine fellows' attitudes and skills improved significantly after the longitudinal clinical experience. The faculty survey demonstrated improved documentation, communication, and fellows' management of on call problems after curriculum implementation. This novel curriculum used role playing to provide training for on-call management of NH residents. This curriculum has been successfully disseminated on a national geriatrics educational resource website (POGOe) and is applicable to geriatric medicine fellowships, internal medicine and family medicine residency programs, and other training programs. PMID- 24219200 TI - Educational interventions to improve recognition of delirium: a systematic review. AB - Delirium is a common and serious condition that is underrecognized in older adults in a variety of healthcare settings. It is poorly recognized because of deficiencies in provider knowledge and its atypical presentation. Early recognition of delirium is warranted to better manage the disease and prevent the adverse outcomes associated with it. The purpose of this article is to review the literature concerning educational interventions focusing on recognition of delirium. The Medline and Cumulative Index to Nursing and Allied Health Literature (CINHAL) databases were searched for studies with specific educational focus in the recognition of delirium, and 26 studies with various designs were identified. The types of interventions used were classified according to the Predisposing, Reinforcing and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model, and outcomes were sorted according to Kirkpatrick's hierarchy. Educational strategies combining predisposing, enabling, and reinforcing factors achieved better results than strategies that included one or two of these components. Studies using predisposing, enabling, and reinforcing strategies together were more often effective in producing changes in staff behavior and participant outcomes. Based on this review, improvements in knowledge and skill alone seem insufficient to favorably influence recognition of delirium. Educational interventions to recognize delirium are most effective when formal teaching is interactive and is combined with strategies including engaging leadership and using clinical pathways and assessment tools. The goal of the current study was to systematically review the published literature to determine the effect of educational interventions on recognition of delirium. PMID- 24219201 TI - Potentially inappropriate medication use in veterans residing in community living centers: have we gotten better? AB - OBJECTIVES: To evaluate the use of medications classified as inappropriate according to the Health Plan Employer Data and Information Set (HEDIS) in elderly veterans residing in Department of Veterans Affairs (VA) nursing homes from 2004 to 2009 and to identify participant-specific correlates of use. DESIGN: Retrospective, cross-sectional study using VA administrative data merged with participant-specific data from the Minimum Data Set. SETTING: VA nursing homes (community living centers (CLCs)). PARTICIPANTS: Veterans aged 65 and older residing in CLCs at the time of the prescribed medication use (N = 176,168). MEASUREMENTS: The number of exposed veterans aged 65 and older per facility receiving at least one HEDIS high-risk medication was determined. RESULTS: Between 2004 and 2009, 28,970 of 176,168 (mean 16.4 +/- 9.5%) veterans received at least one HEDIS high-risk medication. Over the period, the number of veterans receiving high-risk medications decreased steadily from 23.9 +/- 10.0% in 2004 to 10.0 +/- 6.6% in 2009. Nevertheless, large facility variations remained in 2009, with rates from 0% to 44.4%. Certain characteristics were also associated with HEDIS high-risk medication use, including female sex (odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.25-2.04), cancer (OR = 1.19, 95% CI = 1.08-1.32), renal disease (OR = 1.16, 95% CI = 1.01-1.33), chronic obstructive pulmonary disease (OR = 1.16, 95% CI = 1.05-1.28), and diabetes mellitus (OR = 1.11, 95% CI = 1.02-1.22). Protective characteristics included age 75 and older (OR = 0.81, 95% CI = 0.73-0.90) and having a diagnosis of moderate (OR = 0.72, 95% CI = 0.64 0.82) or severe (OR = 0.72, 95% CI = 0.61-0.85) cognitive impairment. CONCLUSION: The use of HEDIS medications among elderly veterans residing in VA nursing homes has markedly improved. Nevertheless, significant variations between facilities and certain subpopulations remain. A low percentage of women at VA CLCs make comparisons with community nursing homes difficult. PMID- 24219202 TI - Preliminary data from an advanced dementia consult service: integrating research, education, and clinical expertise. AB - Hospitalized individuals with advanced dementia often receive care that is of limited clinical benefit and inconsistent with preferences. An advanced dementia consultation service was designed, and a pre and post pilot study was conducted in a Boston hospital to evaluate it. Geriatricians and a palliative care nurse practitioner conducted consultations, which consisted of structured consultation, counseling and provision of an information booklet to the family, and postdischarge follow-up with the family and primary care providers. Individuals aged 65 and older with advanced dementia who were admitted were identified, and consultations were solicited using pop-ups programmed into the computerized provider order entry (POE) system. In the initial 3-month period, 24 subjects received usual care. In the subsequent 3-month period, consultations were provided to five subjects for whom they were requested. Data were obtained from the electronic medical record and proxy interviews (admission, 1 month after discharge). Mean age of the combined sample (N = 29) was 85.4, 58.6% were from nursing homes, and 86.2% of their proxies stated that comfort was the goal of care. Nonetheless, their hospitalizations were characterized by high rates of intravenous antibiotics (86.2%), more than five venipunctures (44.8%), and radiological examinations (96.6%). Acknowledging the small sample size, there were trends toward better outcomes in the intervention group, including greater proxy knowledge of the disease, better communication between proxies and providers, more advance care planning, lower rehospitalization rates, and fewer feeding tube insertions after discharge. Targeted consultation for advanced dementia is feasible and may promote greater engagement of proxies and goal directed care after discharge. PMID- 24219203 TI - Paying the price: the pressing need for quality, cost, and outcomes data to improve correctional health care for older prisoners. AB - Despite a recent decline in the U.S. prison population, the older prisoner population is growing rapidly. U.S. prisons are constitutionally required to provide health care to prisoners. As the population ages, healthcare costs rise, states are forced to cut spending, and many correctional agencies struggle to meet this legal standard of care. Failure to meet the healthcare needs of older prisoners, who now account for nearly 10% of the prison population, can cause avoidable suffering in a medically vulnerable population and violation of the constitutional mandate for timely access to an appropriate level of care while incarcerated. Older prisoners who cannot access adequate health care in prison also affect community healthcare systems because more than 95% of prisoners are eventually released, many to urban communities where healthcare disparities are common and acute healthcare resources are overused. A lack of uniform quality and cost data has significantly hampered innovations in policy and practice to improve value in correctional health care (achieving desired health outcomes at sustainable costs). With their unique knowledge of complex chronic disease management, experts in geriatrics are positioned to help address the aging crisis in correctional health care. This article delineates the basic health, cost, and outcomes data that geriatricians and gerontologists need to respond to this crisis, identifies gaps in the available data, and anticipates barriers to data collection that, if addressed, could enable clinicians and policy-makers to evaluate and improve the value of geriatric prison health care. PMID- 24219206 TI - Therapeutic effects of exercise on cognitive function. PMID- 24219204 TI - Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of Older Adults with Diabetes Mellitus: 2013 update. PMID- 24219205 TI - Management of cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: 2002-2012 literature review. AB - Type 2 diabetes mellitus (DM) is one of the most common chronic conditions in older adults and is often accompanied by comorbidities and geriatric syndromes. The management of cardiovascular disease risk factors in older adults with DM is important to clinicians. The literature was reviewed from 2002 to 2012 to provide an American Geriatrics Society expert panel with an evidence base for updating and making new recommendations for improving the care of older adults with type 2 DM. This review includes only the domains of the management of blood pressure, lipid control, glycemic control, and use of aspirin. Over the last 10 years, new randomized controlled trials (RCT) designed to study different blood pressure treatment targets did not find evidence that intensive systolic blood pressure control (<130 mmHg) resulted in lower rates of myocardial infarction and mortality than less-intensive control. There are risks of side effects with achieving systolic blood pressure of less than 120 mmHg. Lipid-lowering statins are effective in reducing cardiovascular events in middle-aged and older adults, but data on niacin and fibrates is limited. Trials of statins and other lipid lowering agents do not evaluate the cardiovascular effects on outcomes from treating lipids to different low-density lipoprotein cholesterol targets. No RCTs of lipid-lowering drugs enrolled significant numbers of adults aged 80 and older with or without DM. Three major RCTs that investigated intensive glycemic control did not find reductions in primary cardiovascular endpoints, and one study reported greater mortality with glycosylated hemoglobin of less than 6%. Two recently published RCTs were designed to study the cardiovascular benefits of aspirin use by individuals with DM. Neither trial found significantly fewer primary cardiovascular endpoints with aspirin than in control groups. Overall, RCTs enrolled few adults aged 80 and older or with significant comorbidities. More research is needed for clinicians to effectively customize care to older adults with DM because of heterogeneity in health status, comorbidities, duration of disease, frailty and functional status, and differences in life expectancy. PMID- 24219207 TI - It's time for a talk about measuring cost and corrections. PMID- 24219208 TI - The Vulnerable Elders Survey-13 predicts mortality in older adults with later stage colorectal cancer receiving chemotherapy: a prospective pilot study. PMID- 24219209 TI - Antinuclear antibodies and rheumatoid factor positivity in healthy elderly adults: a cross-sectional study in 336 individuals. PMID- 24219210 TI - Evaluation of primary nonadherence to oral bisphosphonate therapy. PMID- 24219211 TI - Vertebral fractures in elderly adults: atypical presentation rather than asymptomatic. PMID- 24219212 TI - All-cause mortality in elderly adults diagnosed with cardiorenal syndrome after an internal medicine unit admission. PMID- 24219213 TI - Severe sensory neuropathy increases risk of heel pressure ulcer in older adults. PMID- 24219214 TI - Risk of proton pump inhibitor-induced mild hyponatremia in older adults. PMID- 24219215 TI - Ageism in interventional stroke studies. PMID- 24219216 TI - Sundowning syndrome and hypothalamic-pituitary-adrenal axis dysregulation in individuals with Alzheimer's disease: is there an association? PMID- 24219217 TI - Acquired hemophilia in a nonagenarian: a case report. PMID- 24219218 TI - A diagnosis of idiopathic basal ganglia calcification in an 82-year-old man. PMID- 24219219 TI - Mortals who are reconciled to being mortal. PMID- 24219220 TI - Response letter to Thomas Finucane, MD. PMID- 24219221 TI - Response to Thomas Finucane. PMID- 24219222 TI - Periodontitis, edentulism, and dementia. PMID- 24219223 TI - Sustainable energy recovery in wastewater treatment by microbial fuel cells: stable power generation with nitrogen-doped graphene cathode. AB - Microbial fuel cells (MFCs) recover energy sustainably in wastewater treatment. Performance of non-noble cathode catalysts with low cost in neutral medium is vital for stable power generation. Nitrogen-doped graphene (NG) as cathode catalyst was observed to exhibit high and durable activity at buffered pH 7.0 during electrochemical measurements and in MFCs with respect to Pt/C counterpart. Electrochemical measurements showed that the oxygen reduction reaction (ORR) on NG possessed sustained activity close to the state-of-art Pt/C in terms of onset potential and electron transfer number. NG-MFCs displayed maximum voltage output of 650 mV and maximum power density of 776 +/- 12 mW m(-2), larger than 610 mV and 750 +/- 19 mW m(-2) of Pt/C-MFCs, respectively. Furthermore, long-time test lasted over 90 days, during which the maximum power density of NG-MFCs declined by 7.6%, with stability comparable to Pt/C-MFCs. Structure characterization of NG implied that the relatively concentrated acidic oxygen-containing groups improved such long-time stability by repelling the protons due to the same electrostatic force, and thus the C-N active centers for ORR were left undestroyed. These findings demonstrated the competitive advantage of NG to advance the application of MFCs for recovering biomass energy in treatment of wastewater with neutral pH. PMID- 24219224 TI - Behavior of lyophilized biological valves in a chronic animal model. AB - Glutaraldehyde is used in order to improve the mechanical and immunogenic properties of biological tissues, such as bovine pericardium membranes, used to manufacture heart valve bioprostheses. Lyophilization, also known as freeze drying, preserves biological material without damage by freezing the water content and removing ice by sublimation. Through this process, dehydrated products of high quality may be obtained; also, the material may be easily handled. The lyophilization process reduces aldehyde residues in biological tissue previously treated with glutaraldehyde, thus promoting reduction of cytotoxicity, increasing resistance to inflammation, and possibly decreasing the potential for tissue calcification. The objective of this study was to chronically evaluate the calcification of bovine pericardium heart valve prostheses, previously lyophilized or not, in an animal model. Six-month-old sheep received implants of lyophilized and unlyophilized heart valve prostheses in the pulmonary position with right bypass. The study followed 16 animals for a period of 90 days. Right ventricle-pulmonary artery (RV/PA) transvalvular pressure gradient was evaluated before and immediately after implantation and before explantation, as were tissue calcium, inflammation intensity, and thrombosis and pannus formation. The t-test was used for statistical analysis. Twelve animals survived to the end of the experiment, but one of the animals in the control group had endocarditis and was excluded from the data. Four animals died early. The mean RV/PA gradient on implantation was 2.0 +/- 1.6 mm Hg in the control group and 6.2 +/- 4.1 mm Hg in the lyophilized group (P = 0.064). This mean gradient increased at explantation to 7.7 +/- 3.9 mm Hg and 8.6 +/- 5.8 mm Hg, respectively (P = 0.777). The average calcium content in the tissue leaflets after 3 months was 21.6 +/- 39.1 mg Ca(2+)/g dry weight in the control group, compared with an average content of 41.2 +/- 46.9 mg Ca(2+)/g dry weight in the lyophilized group (P = 0.478). In this experimental study there was no reduction of calcification after lyophilization. However, histological analysis showed less inflammation over the lyophilized tissue when compared with the control. PMID- 24219225 TI - Association of OSMR gene polymorphisms with rheumatoid arthritis and systemic lupus erythematosus patients. AB - Cytokines are involved in the pathogenesis of autoimmune diseases. Oncostatin M receptor (OSMR) activates JAK/STAT and MAPK pathways leading to the stimulation of a variety of cytokines and inflammatory substances. Many pro-inflammatory cytokines are involved in the inflammatory process of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we carried out experiments to examine the relationship of OSMR promoter polymorphisms with RA and SLE patients. 241 patients of RA, 143 patients of SLE and 203 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphism was genotyped by TaqMan real-time polymerase chain reaction. The OMSR promoter region -100 G/T (rs22922016) genotype was in no relation to the susceptibility of RA, but -100 T/T (rs22922016) genotype could prevent the patients with sicca syndrome and the existence of anti-Ro antibodies. In contrast, the -100 G/T+T/T (rs22922016) genotypes were significantly associated with an increased risk of SLE (odds ratio, OR=1.62, 95% confidence interval (CI), 1.01-2.62). 94.38% of SLE patients with arthritis were belonged to the -1687C/C (rs540558) genotype. The T allele of promoter region -100 T/T (rs22922016) has protective effect and could ameliorate the disease condition in RA patients, whereas the same T allele was a risk allele in the susceptibility of SLE. The disease severity of rheumatoid arthritis and systemic lupus erythematosus can be partially affected by the OSMR promoter polymorphisms. PMID- 24219227 TI - A multicentre matched-pair analysis comparing robot-assisted versus open partial nephrectomy. AB - OBJECTIVE: To compare the perioperative, pathological and functional outcomes in two contemporary, large series of patients in different institutions and who underwent open partial nephrectomy (OPN) or robot-assisted PN (RAPN) for suspected renal tumours. PATIENTS AND METHODS: This was a retrospective, multicentre, international, matched-pair analysis comparing patients who underwent RAPN or OPN for suspected renal cell carcinoma. Data on patients who underwent OPN were extracted by an Italian observational registry collecting data from 19 different centres. Data on patients who received RAPN were extracted from a multicentre, international database collecting cases treated in four high volume referral centres of robotic surgery. The matching was in a 1:1 ratio for the surgical approach and included 200 patients in each arm. RESULTS: The mean warm ischaemia time was shorter in the OPN group than in the RAPN group, at a mean (SD) of 15.4 (5.9) vs 19.2 (7.3) min (P < 0.001). Conversely, the median (interquartile range) estimated blood loss was 150 (100-300) mL in the OPN group and 100 (50-150) mL in the RAPN group (P < 0.001). There were no differences in operating time (P = 0.18) and the intraoperative complication rate (P = 0.31) between the approaches. Postoperative complications were recorded in 43 (21.5%) patients who underwent OPN and in 28 (14%) who received RAPN (P = 0.02). Moreover, major complications (grade 3-4) were reported in nine (4.5%) patients after OPN and in nine (4.5%) after RAPN. Positive margins were detected in nine (5.5%) patients after OPN and in nine (5.7%) after RAPN (P = 0.98). The mean (SD) 3-month estimated glomerular filtration rate declined by 16.6 (18.1) mL/min from the preoperative value in the OPN group and by 16.4 (22.9) mL/min in the RAPN group (P = 0.28). CONCLUSION: RAPN can achieve equivalent perioperative, early oncological and functional outcomes as OPN. Moreover, RAPN is a less invasive approach, offering a lower risk of bleeding and postoperative complications than OPN. PMID- 24219228 TI - Chemical composition, nutritional and antioxidant properties of the red edible seaweed Porphyra columbina. AB - Proximate composition, fatty acids and amino acid profiles and nutritional (chemical score, protein digestibility, PDCAAS and mineral dialyzability) and antioxidant properties (TEAC, DPPH and power reduction) from Porphyra columbina were evaluated. Total dietary fiber (48.02 +/- 1.13 g/100 g dry weight) and protein (24.61 +/- 0.21 g/100 g dry weight) were the two most abundant components in this seaweed. The main saturated and unsaturated fatty acids were C16:0 and C20:5 (n-3), respectively. The limiting amino acid was tryptophan with a chemical score of 57%. Protein digestibility was 74.33 +/- 3.0%. Porphyra columbina has high mineral content with good Na/K relationship and medium value of potential mineral accessibility (P, Ca and Zn dializability: 18.75 +/- 0.01, 17.62 +/- 0.16 and 16.70 +/- 0.44, respectively). The highest antioxidant properties were obtained with an acetone/water extraction system. This work provides important information about chemical composition and nutraceutical new properties of P. columbina. PMID- 24219229 TI - Quantifying the temperature dependence of glycine-betaine RNA duplex destabilization. AB - Glycine-betaine (GB) stabilizes folded protein structure because of its unfavorable thermodynamic interactions with amide oxygen and aliphatic carbon surface area exposed during protein unfolding. However, GB can attenuate nucleic acid secondary structure stability, although its mechanism of destabilization is not currently understood. Here we quantify GB interactions with the surface area exposed during thermal denaturation of nine RNA dodecamer duplexes with guanine cytosine (GC) contents of 17-100%. Hyperchromicity values indicate increasing GB molality attenuates stacking. GB destabilizes higher-GC-content RNA duplexes to a greater extent than it does low-GC-content duplexes due to greater accumulation at the surface area exposed during unfolding. The accumulation is very sensitive to temperature and displays characteristic entropy-enthalpy compensation. Since the entropic contribution to the m-value (used to quantify GB interaction with the RNA solvent-accessible surface area exposed during denaturation) is more dependent on temperature than is the enthalpic contribution, higher-GC-content duplexes with their larger transition temperatures are destabilized to a greater extent than low-GC-content duplexes. The concentration of GB at the RNA surface area exposed during unfolding relative to bulk was quantified using the solute partitioning model. Temperature correction predicts a GB concentration at 25 degrees C to be nearly independent of GC content, indicating that GB destabilizes all sequences equally at this temperature. PMID- 24219230 TI - Exploring the aggregation propensity of gammaS-crystallin protein variants using two-dimensional spectroscopic tools. AB - The formation of amyloid fibrils is associated with many serious diseases as well as diverse biological functions. Despite the importance of these aggregates, predicting the aggregation propensity of a particular sequence is a major challenge. We report a joint 2D nuclear magnetic resonance (NMR) and ultraviolet (2DUV) study of fibrillization in the wild-type and two aggregation-prone mutants of the eye lens protein gammaS-crystallin. Simulations show that the complexity of 2DUV signals as measured by their "approximate entropy" is a good indicator for the conformational entropy and in turn is strongly correlated with its aggregation propensity. These findings are in agreement with high-resolution NMR experiments and are corroborated for amyloid fibrils. The 2DUV technique is complementary to high-resolution structural methods and has the potential to make the evaluation of the aggregation propensity for protein variant propensity of protein structure more accessible to both theory and experiment. The approximate entropy of experimental 2DUV signals can be used for fast screening, enabling identification of variants with high fibrillization propensity for the much more time-consuming NMR structural studies, potentially expediting the characterization of protein variants associated with cataract and other protein aggregation diseases. PMID- 24219234 TI - Spatial-memory deficit in schizophrenia spectrum disorders under viewpoint independent demands in the virtual courtyard task. AB - This study builds upon our previous work indicating that impaired hippocampal dependent forms of memory are core to schizophrenia. Using a virtual-reality courtyard task, we presented participants with schizophrenia spectrum disorders (SSD; n = 20) and a healthy community comparison group (n = 20) with objects to remember within a town square, followed by a recognition test of the location of objects from either the same viewpoint or a shifted viewpoint relative to initial presentation. The SSD group demonstrated a relative deficit under shifted- compared to same-view conditions. These findings provide further support for deficient hippocampal-dependent cognition in SSD. PMID- 24219231 TI - Latent class analysis of substance use among adolescents presenting to urban primary care clinics. AB - BACKGROUND: Polysubstance use during adolescence is a significant public health concern. However, few studies have investigated patterns of substance use during this developmental window within the primary care setting. OBJECTIVES: This study used an empirical method to classify adolescents into substance use groups, and examines correlates of the empirically defined groups. METHODS: Data came from patients, ages 12-18 years, presenting to an urban, primary care community health clinics (Federally Qualified Health Centers) in two cities in the Midwestern United States (n = 1664). Latent class analysis (LCA) was used to identify classes of substance users. Multinomial logistic regression was used to examine variables associated with class membership. RESULTS: LCA identified three classes: class 1 (64.5%) exhibited low probabilities of all types of substance use; class 2 (24.6%) was characterized by high probabilities of cannabis use and consequences; and class 3 (10.9%) had the highest probabilities of substance use, including heavy episodic drinking and misuse of prescription drugs. Those in class 2 and class 3 were more likely to be older and have poorer grades, poorer health, higher levels of psychological distress and more sexual partners than those in class 1. Individuals in class 3 were also less likely to be African American than those in class 1. CONCLUSION: Findings provide novel insight into the patterns of substance use among adolescents presenting to low-income urban primary care clinics. Future research should examine the efficacy of interventions that address the complex patterns of substance use and concomitant health concerns among adolescents. PMID- 24219235 TI - Structural and functional changes relevant to maxillary arterial flow observed during computed tomography and nonselective digital subtraction angiography in cats with the mouth closed and opened. AB - Some cats develop blindness during procedures with mouth gags, which possibly relates to maxillary arterial occlusion by opening the mouth. Our first aim was to use computed tomography (CT) to describe how vascular compression is possible based on morphologic differences between mouth positions. Our second aim was to use nonselective digital subtraction angiography to assess whether opening the mouth induces collateral circulation. Six healthy cats were examined. During CT, the maxillary artery coursed between the angular process of the mandible and the rostrolateral wall of the tympanic bulla. The median distance between these structures was shorter when the mouth was opened (left, 4.3 mm; right, 3.6 mm) vs. closed (left, 6.9 mm; right, 7.1 mm). Additionally, the distance was shorter on the side ipsilateral to the gag (P = 0.03). During nonselective angiography, with the mouth closed, there was strong sequential opacification of the external carotid arteries, maxillary arteries, maxillary retia mirabilia, cerebral arterial circle, and basilar artery. Additionally, there was uniform opacification of the cerebrum and cerebellum. With the mouth opened, opacification of the maxillary arteries (rostral to the angular processes) was reduced in all cats, the cerebral arterial circle and basilar artery had simultaneous opacification in four of six (67%) cats, and the cerebrum had reduced opacification compared to the cerebellum in four of six (67%). In conclusion, the maxillary arteries are situated such that they can be compressed when opening the mouth. Opening the mouth did not consistently induce collateral circulation sufficient to produce comparable cerebral opacification as when the mouth was closed. PMID- 24219237 TI - Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. AB - Psychiatric phenotypes are multifactorial and polygenic, resulting from the complex interplay of genes and environmental factors that act cumulatively throughout an organism's lifetime. Adverse life events are strong predictors of risk for a number of psychiatric disorders and a number of studies have focused on gene-environment interactions (GxEs) occurring at genetic loci involved in the stress response. Such a locus that has received increasing attention is the gene encoding FK506 binding protein 51 (FKBP5), a heat shock protein 90 cochaperone of the steroid receptor complex that among other functions regulates sensitivity of the glucocorticoid receptor. Interactions between FKBP5 gene variants and life stressors alter the risk not only for mood and anxiety disorders, but also for a number of other disease phenotypes. In this review, we will focus on molecular and system-wide mechanisms of this GxE with the aim of establishing a framework that explains GxE interactions. We will also discuss how an understanding of the biological effects of this GxE may lead to novel therapeutic approaches. PMID- 24219236 TI - Mitigation of ROS insults by Streptomyces secondary metabolites in primary cortical neurons. AB - Oxidative stress is a common point in neurodegenerative diseases, widely connected with mitochondrial dysfunction. In this study, we screened seven natural products from Streptomyces sources against hydrogen peroxide insult in primary cortical neurons, an oxidative stress in vitro model. We showed the ability of these compounds to inhibit neuronal cytotoxicity and to reduce ROS release after 12 h treatment. Among the tested compounds, the quinone anhydroexfoliamycin and the red pyrrole-type pigment undecylprodigiosin stand out. These two compounds displayed the most complete protection against oxidative stress with mitochondrial function improvement, ROS production inhibition, and increase of antioxidant enzyme levels, glutathione and catalase. Further investigations confirmed that anhydroexfoliamycin acts over the Nrf2-ARE pathway, as a Nrf2 nuclear translocation inductor, and is able to strongly inhibit the effect of the mitochondrial uncoupler FCCP over cytosolic Ca(2+), pointing to mitochondria as a cellular target for this molecule. In addition, both compounds were able to reduce caspase-3 activity induced by the apoptotic enhancer staurosporine, but undecylprodigiosin failed to inhibit FCCP effects and it did not act over the Nrf2 pathway as was the case for anhydroexfoliamycin. These results show that Streptomyces metabolites could be useful for the development of new drugs for prevention of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases and cerebral ischemia. PMID- 24219238 TI - Perspectives on the ethical concerns and justifications of the 2006 Centers for Disease Control and Prevention HIV testing: HIV screening policy changes. AB - BACKGROUND: The 2006 Centers for Disease Control and Prevention (CDC) revised recommendations for HIV testing in clinical settings contained seven specific changes to how health care facilities should provide HIV testing. These seven elements have been both supported and challenged in the lay and medical literature. Our first paper in BMC Medical Ethics presented an analysis of the three HIV testing procedural changes included in the recommendations. In this paper, we address the four remaining elements that concern HIV screening policy changes: (1) nontargeted HIV screening, (2) making HIV screening similar to screening for other treatable conditions, (3) increasing HIV screening without assured additional funding for linkage to care, and (4) making patients bear the costs of increased HIV screening in health care settings. METHODS: We interviewed 25 members from the fields of US HIV advocacy, care, policy, and research about the ethical merits and demerits of the four changes to HIV screening policies. We performed a qualitative analysis of the participant responses in the interviews and summarized the major themes. RESULTS: Participants commented that nontargeted HIV screening and making HIV screening similar to screening for other treatable medical conditions was ethical when it broadened the scope of people being tested for HIV. However, they believed it was unethical when it did not respect the exceptional nature of HIV and HIV testing. Some participants favored more testing regardless if there was assured additional funding for linkage to care or if patients might bear the costs of testing because they believed that merely alerting patients of their status was beneficial and would lead to positive consequences. Other participants found ethical flaws with testing without assured linkage to care and patients bearing the costs of testing, as this could discriminate against those who could not pay. CONCLUSIONS: Our findings suggest that there are fundamental ethical disagreements that shape views on CDC's recommended HIV testing policies. Differences remain on whether or not HIV remains an exceptional condition that requires it to be treated differently than other treatable conditions. Disagreement also exists on the responsibilities of health care providers and rights of patients in regards to screening in (1) the absence of assured linkage to care after an HIV diagnosis and (2) paying for the costs of HIV screening. Resolution of these disagreements is needed to serve the common goal of using testing to facilitate medical care for those who are HIV infected and for reducing HIV transmission. PMID- 24219239 TI - Anxiety reactivity and anxiety perseveration represent independent dimensions of anxiety vulnerability: an in vivo study. AB - Trait anxiety is a relatively stable disposition reflecting an individual's tendency to experience anxious symptomatology, typically measured using questionnaires such as the Spielberger Trait Anxiety Inventory (STAI-T). While trait anxiety commonly is considered a unitary construct, recent questionnaire research suggests that two different dimensions of anxiety vulnerability account for independent variance in trait anxiety scores. These dimensions are anxiety reactivity (AR), reflecting the intensity of anxiety reactions to stressors, and anxiety perseveration (AP), reflecting the persistence of anxiety symptoms. This study investigated whether in vivo measures of these two facets independently contribute to anxiety vulnerability. Seventy-two participants were exposed to a novel stress task designed to yield measures of AR and AP. Regression analysis determined that these in vivo measures were unrelated to each other, and each accounted for independent variance in trait anxiety scores. The implications of these findings for the assessment and understanding of anxiety vulnerability are discussed. PMID- 24219240 TI - Evaluation of left ventricular diastolic function by global strain rate imaging in patients with obstructive hypertrophic cardiomyopathy: a simultaneous speckle tracking echocardiography and cardiac catheterization study. AB - BACKGROUND: Impaired left ventricular (LV) diastolic function is a common pathophysiological feature of patients with hypertrophic cardiomyopathy (HCM). The noninvasive evaluation of diastolic function in these patients remains a challenge. Speckle tracking echocardiography (STE) provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in HCM patients. METHODS AND RESULTS: We retrospectively analyzed 51 patients with obstructive HCM (HOCM). Strain rate (SR) curves were obtained for 18 different segments of the LV myocardium. The peak SR during the isovolumic relaxation period (SRIVR ) and the peak early diastolic strain rate (SRE ) were measured for each segment. Cardiac catheterization was performed within 24 hours after echocardiographic analysis. LV end-diastolic pressure (LVEDP) was measured and time constant of myocardial relaxation (tau) was calculated. We therefore correlated STE-derived with invasive indices and compared it with flow and tissue Doppler measurements. SRIVR and SRE were significantly reduced in all 51 HOCM patients (0.16 +/- 0.09%/sec and 0.71 +/- 0.25%/sec).The ratio of peak early mitral inflow velocities to SRIVR and SRE (E/SRIVR and E/SRE ) correlated well with LVEDP (r = 0.760, P < 0.001; r = 0.401, P = 0.004). Receiver operating characteristic analysis shown E/SRE ratio had the largest under curve area in predicting HOCM patients with seriously elevated LVEDP. In addition, SRIVR and SRE significantly related with tau (r = -0.611, P < 0.001; r = -0.369, P = 0.008). CONCLUSIONS: Diastolic function was seriously impaired in HOCM patients. The E/SRE ratio can be used to predict LVEDP with acceptable accurate in HOCM patients. In addition, SRIVR is a reliable parameter to assess LV relaxation in patients with HOCM. PMID- 24219241 TI - Diversity-oriented approaches to unusual alpha-amino acids and peptides: step economy, atom economy, redox economy, and beyond. AB - Here we describe several useful strategies to a variety of unusual alpha-amino acid derivatives and peptides based on "building block" approach. These building blocks are suitable for modification at an amino acid as well as at a peptide level. Moreover, these methods have embedded several points for diversification and are capable of producing a library of modified amino acids and peptides. We have employed highly atom-economic processes such as the Diels-Alder reaction, [2 + 2 + 2] cycloaddition, Suzuki-Miyaura cross-coupling, and olefin metathesis as key steps to assemble various unnatural amino acid derivatives and peptides. In some instances, we have used rongalite to generate Diels-Alder precursors. PMID- 24219242 TI - The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells. AB - Recently, the involvement of PIN1, a peptidyl-prolyl cis/trans isomerase, has been reported in age-related bone homeostasis and adipogenesis. However, the role of PIN1 during odontogenic and adipogenic differentiation remains to be fully understood, particularly regarding human dental pulp stem cells (HDPSCs). Thus, in the present study, we have investigated the role of PIN1 in odontogenic and adipogenic differentiation of HDPSCs and signaling pathways possibly involved. PIN1 mRNA and protein level were upregulated in a time-dependent manner during adipogenic differentiation, increasing until 1 day of odontogenic induction and then steadily declined during odontogenic differentiation. Treatment of a known PIN1 inhibitor, juglone, significantly increased odontogenic differentiation as confirmed by alkaline phosphatase (ALP) activity, calcium deposition, and mRNAs induction of odontogenic markers [ALP, osteopontin (OPN), osteocalcin (OCN), dentin sialophosphoprotein (DSPP), and dentin matrix protein 1 (DMP-1)]. On the contrary, adipogenic differentiation was dramatically reduced upon juglone treatment, with concomitant downregulation of lipid droplet accumulation and adipogenic marker genes [peroxisome proliferation-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (AP2)]. In contrast to PIN1 inhibition, the overexpression of PIN1 via adenoviral infection (Ad-PIN1) in HDPSCs inhibited odontogenic differentiation but increased adipogenic differentiation, in which stem cell property markers such as stage specific embryonic antigen-4 (SSEA-4) and STRO-1 were upregulated during odontogenic differentiation but downregulated in adiopogenic differentiation. Consistently, juglone-mediated inhibition of PIN1 augmented the osteogenic medium (OM)-induced activation of bone morphogenetic protein (BMP), Wnt/beta-catenin, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-kappaB) pathway, which response was reversed by Ad PIN1. Moreover, juglone blocked the adipogenic induction medium-induced activation of PPARgamma, C/EBPalpha, C/EBPbeta, ERK, and NF-kappaB pathways, which was rescued by Ad-PIN1 infection. In summary, the present study shows for the first time that PIN1 acts as an important modulator of odontogenic and adipogenic differentiation of HDPSCs and may have clinical implications for regenerative dentistry. PMID- 24219243 TI - Combined delivery of BCNU and VEGF siRNA using amphiphilic peptides for glioblastoma. AB - Combined delivery of chemical drug and therapeutic gene has been introduced as an efficient method for the treatment of cancers such as glioblastoma. In this study, bis-chloroethylnitrosourea (BCNU) and vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA) were co-delivered into C6 glioblastoma cells using a non-toxic peptide-based carrier. The R3V6 peptides, which are composed of 3-arginine and 6-valine, formed self-assembled micelles in aqueous solution. BCNU, a hydrophobic anti-cancer drug, was loaded into the hydrophobic core of the micelles, forming BCNU-loaded R3V6 micelles (R3V6-BCNU). In gel retardation assay, R3V6-BCNU formed a stable complex with siRNA. In vitro transfection assay showed that the VEGF-siRNA/R3V6-BCNU complex had the highest transfection efficiency into C6 cells at a 1:20 weight ratio (VEGF-siRNA:R3V6 BCNU). In addition, the VEGF-siRNA/R3V6-BCNU complexes had higher delivery efficiency than lipofectamine or naked siRNA. VEGF expressions were remarkably decreased by transfection of the VEGF-siRNA/R3V6 or VEGF-siRNA/R3V6-BCNU complexes. Furthermore, R3V6-BCNU delivered BCNU more efficiently into the cells than BCNU only. Therefore, R3V6 delivered both VEGF-siRNA and BCNU efficiently into the glioblastoma cells. The results suggest that R3V6-BCNU may be useful for combined delivery of siRNA and chemical drug into cancer cells. PMID- 24219244 TI - The use of high-frequency ultrasound imaging and biofluorescence for in vivo evaluation of gene therapy vectors. AB - BACKGROUND: Non-invasive imaging of the biodistribution of novel therapeutics including gene therapy vectors in animal models is essential. METHODS: This study assessed the utility of high-frequency ultrasound (HF-US) combined with biofluoresence imaging (BFI) to determine the longitudinal impact of a Herpesvirus saimiri amplicon on human colorectal cancer xenograft growth. RESULTS: HF-US imaging of xenografts resulted in an accurate and informative xenograft volume in a longitudinal study. The volumes correlated better with final ex vivo volume than mechanical callipers (R2 = 0.7993, p = 0.0002 vs. R2 = 0.7867, p = 0.0014). HF-US showed that the amplicon caused lobe formation. BFI demonstrated retention and expression of the amplicon in the xenografts and quantitation of the fluorescence levels also correlated with tumour volumes. CONCLUSIONS: The use of multi-modal imaging provided useful and enhanced insights into the behaviour of gene therapy vectors in vivo in real-time. These relatively inexpensive technologies are easy to incorporate into pre-clinical studies. PMID- 24219246 TI - Top-down and bottom-up aspects of active search in a real-world environment. AB - Visual search has been studied intensively in the labouratory, but lab search often differs from search in the real world in many respects. Here, we used a mobile eye tracker to record the gaze of participants engaged in a realistic, active search task. Participants were asked to walk into a mailroom and locate a target mailbox among many similar mailboxes. This procedure allowed control of bottom-up cues (by making the target mailbox more salient; Experiment 1) and top down instructions (by informing participants about the cue; Experiment 2). The bottom-up salience of the target had no effect on the overall time taken to search for the target, although the salient target was more likely to be fixated and found once it was within the central visual field. Top-down knowledge of target appearance had a larger effect, reducing the need for multiple head and body movements, and meaning that the target was fixated earlier and from further away. Although there remains much to be discovered in complex real-world search, this study demonstrates that principles from visual search in the labouratory influence gaze in natural behaviour, and provides a bridge between these labouratory studies and research examining vision in natural tasks. PMID- 24219245 TI - Differentiating amino acid residues and side chain orientations in peptides using scanning tunneling microscopy. AB - Single-molecule measurements of complex biological structures such as proteins are an attractive route for determining structures of the large number of important biomolecules that have proved refractory to analysis through standard techniques such as X-ray crystallography and nuclear magnetic resonance. We use a custom-built low-current scanning tunneling microscope to image peptide structures at the single-molecule scale in a model peptide that forms beta sheets, a structural motif common in protein misfolding diseases. We successfully differentiate between histidine and alanine amino acid residues, and further differentiate side chain orientations in individual histidine residues, by correlating features in scanning tunneling microscope images with those in energy optimized models. Beta sheets containing histidine residues are used as a model system due to the role histidine plays in transition metal binding associated with amyloid oligomerization in Alzheimer's and other diseases. Such measurements are a first step toward analyzing peptide and protein structures at the single molecule level. PMID- 24219247 TI - Initial investigations into preschoolers' mirror-style versus transposed bodily imitation. AB - In typical development, imitation plays a key role in sociocognitive competence. The current study investigated a hypothesised developmental trajectory in face-to face full body imitation style in 91 preschoolers, as well as a relation between imitation style and theory of mind (ToM). Children's response style to 8 lateralized action prompts was recorded as either "mirror" or "transposed." Overall, mirror-style response increased with age, and was predominant for children and an adult comparison group. Imitation style varied depending on the prompt given, with certain actions showing a side bias regardless of prompt viewed. Mirror-style response was correlated with ToM performance after controlling for language ability, but not after controlling for age. Findings are discussed regarding the hypothesised relation between postural synchrony and larger perspective-taking competence. PMID- 24219248 TI - The alpha1,3GalT knockout/alpha1,2FucT transgenic pig does not appear to have an advantage over the alpha1,3GalT knockout pig with respect to glycolipid reactivity with human serum antibodies. AB - BACKGROUND: The human H-transferase (alpha2FucT) was introduced in Gal-negative pigs to produce pig organs not only free from Gal-antigens, but also in which the uncapped N-acetyllactosamine precursor had been transformed into non-xenogenic blood group H type 2 compounds. This work is the first descriptive analysis of glycolipids from the GalT-KO/FucT-TG pig. The aim was to investigate the cell membrane antigens in GalT-KO/FucT-TG tissues to explore its efficacy as an organ donor. Also, detailed knowledge on the correlation between the cellular glycosyltransferase configuration and the resulting carbohydrate phenotype expression is valuable from a basic glycobiological perspective. METHODS: Neutral and acidic glycolipids from GalT-KO/FucT-TG small intestine were compared with glycolipids from two wildtype and two GalT-KO pig intestines. Glycolipid reactivity was tested on thin layer chromatography plates using chemical reagents, antibodies, lectins, and human serum. Structural characterization of neutral glycolipids was performed by LC-ESI/MS and proton NMR spectroscopy. RESULTS: Characterization of the glycolipid expression in GalT-KO/FucT-TG intestine showed absence of Gal antigens and decreased/unchanged levels of the N acetyllactosamine precursor and the blood group H type 2 expression, when compared with the wildtype. The reactivity of human serum antibodies to GalT KO/FucT-TG derived glycolipids was similar or slightly elevated when compared with GalT-KO glycolipids. Results from LC-ESI/MS and proton NMR spectroscopy revealed no established neutral xenogenic antigens in the GalT-KO/FucT-TG pig, and could thus not explain the immunologic reactivity to human serum antibodies. The antibody binding to acidic glycolipids is most likely to be explained by the abundance of N-glycolylneuraminic acid epitopes in pig tissues. Six neutral complex biantennary glycolipids with blood group H type 1, 2, Lewis(x) and Lewis(y) determinants were found, of which three were identified in this work for the first time. One of these was a nonaglycosylceramide with blood group H type 2 and lactosyl determinants linked to a lactotetraosyl core, and the other two were decaglycosylceramides with blood group H type 1 and H type 2 determinants linked to a neolactotetraosyl core, and Lewis(x) and blood group H type 1 determinants on a lactotetraosyl core, respectively. CONCLUSIONS: Lipid-linked carbohydrate antigens in the GalT-KO/FucT-TG pig intestine showed no or minor qualitative difference when compared with GalT-KO pigs. The GalT-KO/FucT-TG pig did not appear to have an advantage over the GalT-KO pig with respect to reactivity with human antibodies from a xenotransplantation perspective. PMID- 24219249 TI - Pain policy and abuse of prescription opioids in the USA: a cautionary tale for Europe. PMID- 24219250 TI - Lost in translation? Learning from the opioid epidemic in the USA. PMID- 24219251 TI - A randomised controlled trial comparing the GlideScope((r)) and the Macintosh laryngoscope for double-lumen endobronchial intubation. AB - Double-lumen endobronchial tubes are the most common method of achieving lung isolation and one-lung ventilation during thoracic anaesthesia and surgery. We compared the clinical performance of the Macintosh laryngoscope and the GlideScope((r)) during endobronchial intubation with a double-lumen tube. Seventy patients with no predictors for difficult laryngoscopy were allocated randomly to the Macintosh laryngoscope or GlideScope. The time taken for endobronchial intubation with the Macintosh laryngoscope was significantly shorter compared with that taken for the GlideScope, median (IQR [range]) 33 (22-52 [11-438]) s vs 70 (39-129 [21-242]) s, respectively, p = 0.0013. There was no statistical difference in the rate of success at the first attempt (91% vs 83%, respectively). On a numerical rating scale (scored from 0 to 10), the 30 anaesthetists who took part in the study rated endobronchial intubation overall as easier using the Macintosh compared with the GlideScope, 2 (1-3 [0-8]) vs 3 (2 6 [0-10]), respectively, p = 0.003. Postoperative voice changes were also less common in the Macintosh group (8 (22%) vs 17 (58%), p = 0.045). Anaesthetists found the GlideScope more difficult to use than the Macintosh laryngoscope and endobronchial intubation took longer; therefore, we cannot recommend its routine use with double-lumen tubes in patients who are predicted to have a normal airway. PMID- 24219252 TI - A laboratory study of the effects of processing blood through a cell salvage device and leucocyte depletion filter on levels of pro-inflammatory cytokines and bradykinin. AB - We investigated changes in concentrations of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and bradykinin in blood during passage through a cell salvage device and a leucocyte depletion filter, with or without application of subatmospheric pressure across the filter. Blood samples from 19 healthy women undergoing scheduled caesarean section showed concentrations of cytokines and bradykinin in blood filtered under gravity flow that were equal to or significantly lower than those of pre-operative venous blood samples. They were also significantly lower than that in postoperative orthopaedic shed blood, which is commonly reinfused after orthopaedic surgery. A minority of samples taken from blood that had been filtered using subatmospheric pressure showed raised interleukin-6 concentrations. We suggest that use of a leucocyte depletion filter for cell-salvaged blood with gravity flow is likely to be safe with regard to concentrations of cytokines and bradykinin. However, this may not hold true for the filter used with subatmospheric pressure. If transfusion of salvaged blood using a leucocyte depletion filter seems to induce hypotension, elevation of interleukin-6 should be suspected. PMID- 24219254 TI - Pre-operative nerve blocks for hip fracture - 1. PMID- 24219255 TI - Pre-operative nerve blocks for hip fracture - 3. PMID- 24219256 TI - Pre-operative nerve blocks for hip fracture - 2. PMID- 24219257 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 4. PMID- 24219258 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 6. PMID- 24219259 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 5. PMID- 24219260 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 7. PMID- 24219261 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 9. PMID- 24219262 TI - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck fracture - 8. PMID- 24219263 TI - Peri-operative fitness: a question of stamina? PMID- 24219264 TI - A reply. PMID- 24219265 TI - Entrapment of power cable. PMID- 24219266 TI - Brain oxygenation - does raised intracranial pressure play a role? PMID- 24219267 TI - Two stuck epidural catheters. PMID- 24219268 TI - Transient paralysis after cyclizine administration. PMID- 24219269 TI - A response from the manufacturers. PMID- 24219270 TI - Transient paralysis after cyclizine administration. PMID- 24219271 TI - Guidelines and use of dexamethasone for postoperative nausea and vomiting. PMID- 24219272 TI - A reply. PMID- 24219273 TI - Regional anaesthesia and patients with abnormalities of coagulation. PMID- 24219274 TI - A reply. PMID- 24219275 TI - Understanding processes of change: how some patients reveal more than others-and some groups of therapists less-about what matters in psychotherapy. AB - OBJECTIVE: We identify difficulties researchers encounter in psychotherapy process-outcome investigations, and we describe several limitations of the popular "variance accounted for" approach to understanding the effects of psychotherapy. METHODS & RESULTS: Using data simulations, we show how the expected correlation between an excellent measure of therapy quality and outcome would be surprisingly small (approximately .25) under conditions likely to be common in psychotherapy research. Even when we modeled conditions designed to increase the likelihood that strong process-outcome relationships would be observed, we found that the expected correlations were still only in the modest range (.38-.51). CONCLUSIONS: We discuss the implications of our analysis for the interpretation of process-outcome findings as well as for design considerations in future investigations. PMID- 24219277 TI - The epigenetic potentials of dietary polyphenols in prostate cancer management. AB - Prostate cancer is a disease that is greatly affected by lifestyle, particularly diet, and is more prevalent in US and European countries compared with South and East Asia. Among several known causes and risk factors, nutrition plays an important role in prostate cancer pathogenesis. Various dietary components including polyphenols have been shown to possess anticancer properties. Dietary polyphenols have been the subject of extensive studies for the last decade because of their anticancer and chemopreventive potentials. Besides possessing various antitumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Various polyphenols have been shown to affect DNA methylation, histone posttranslational modifications, and microRNA expression patterns in prostate cancer. In this review, we discuss the contribution of dietary polyphenols to various epigenetic modifications in prostate cancer. Since prostate cancer and diet are intimately associated, polyphenol-rich diets that epigenetically modify tumor biology have great significance in the prevention and management of prostate cancer. PMID- 24219276 TI - Pathological pigmentation in cardiac tissues of Atlantic salmon (Salmo salar L.) with cardiomyopathy syndrome. AB - It is widely accepted that melanin formation may play an immunologic role in invertebrates and ectothermic vertebrates. In farmed Atlantic salmon, cardiomyopathy syndrome (CMS) is a common viral disease associated with severe cardiac inflammation that may be accompanied by heavy melanisation of the heart. By the use of histology, laser capture microdissection and transcription analysis of tyrosinase genes, we here show that this melanisation is linked to de novo melanogenesis by melanomacrophages, suggesting an active part in the inflammatory reaction. No general systemic activation of the extracutaneous pigmentary system in response to viral infections with affinity to the heart was observed. PMID- 24219278 TI - The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression. AB - The Jumonji D2 proteins (JMJD2/KDM4) function to demethylate di- and trimethylated (me2/3) histone 3 lysine 9 (H3K9me2/3) and H3K36me3. Knockout mouse models for Kdm4b and Kdm4d have not resulted in gross abnormalities, while mouse models for Kdm4a and Kdm4c have not been reported. However, the KDM4 subfamily of demethylases are overexpressed in several tumor types. Overexpression of KDM4 proteins alters transcription and chromatin remodeling, driving cellular proliferation, anchorage-independent growth, invasion, and migration. Increased proliferation occurs through KDM4-mediated modification of cell cycle timing, as well as through increased numbers of replication forks. Recent evidence also suggests that KDM4C overexpression contributes to the maintenance of a pluripotent state. Together these data suggest that overexpression of KDM4 proteins induces numerous oncogenic effects. PMID- 24219279 TI - Hitchhiker antigens: inconsistent ChIP results, questionable immunohistology data, and poor antibody performance may have a common factor. AB - Questionable data and poor antibody performance may have a common factor: antigens "hitchhiking" on the very antibodies designed to target them. Here I focus on histone hitchhikers and their antibodies, given the impact of chromatin immunoprecipitation on our understanding of DNA regulation. Caused by a lack of stringency during antibody purification, hitchhikers will impede important advances in chromatin research and therapeutics derived from that research, if similar circumstances in the study of lupus decades ago are any guide. Evidence of this phenomenon is reviewed, purification modifications for antibody manufacturing are suggested, and a histone hitchhiker detection procedure is provided. PMID- 24219281 TI - Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer. AB - This study investigated the therapeutic effect of crocetin, a carotenoid derived from saffron, on gastric adenocarcinoma (AGS) cells and 1-methyl-3-nitro-1 nitrosoguanidine (MNNG)-induced gastric cancer in rats. An MTT assay showed a significant dose- and time-dependent inhibition of AGS cell proliferation as a result of crocetin administration. Flow cytometry and caspases activity assays revealed apoptosis had been induced in these cells; RT-PCR and Western blot analyses revealed the suppression of Bcl-2 and up-regulation of Bax expression in AGS cells treated with crocetin. These changes were not observed in normal human fibroblast (HFSF-PI3) cells. Pathological study of the tumor tissue in MNNG induced gastric cancer in rats indicated the dose-dependent inhibition of tumor progression. In addition, crocetin reversed some changed biochemical parameters, including serum antioxidant activity and lactate dehydrogenase in rat serum. The present study demonstrates the antioxidant, anti-proliferative, and apoptotic activities of crocetin against gastric cancer that may benefit human stomach cancer treatment. PMID- 24219283 TI - Comparative in vitro evaluation of transportability and toxicity of capecitabine and its metabolites in cells derived from normal human kidney and renal cancers. AB - The goal of this study was to understand roles of nucleoside and nucleobase transport processes in capecitabine pharmacology in cells derived from human renal proximal tubule cells (hRPTCs) and three human renal cell carcinoma (RCC) cell lines, A498, A704, and Caki-1. Human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) mediated activities and a sodium-independent nucleobase activity were present in hRPTCs. In hRPTCs, uptake of 5'-deoxy-5-fluorouridine (DFUR), a nucleoside metabolite of capecitabine, was pH dependent with highest uptake seen at pH 6.0. In RCC cell lines, hENT1 was the major nucleoside transporter. Nucleobase transport activity was variable among the three RCC cell lines, with Caki-1 showing the highest and A498 showing the lowest activities. Treatment of RCC cell lines with interferon alpha (IFN-alpha) increased thymidine phosphorylase levels and prior treatment of RCC cell lines with IFN-alpha followed by 5-FU or DFUR resulted in enhanced sensitivity of all cell lines to 5 FU and two of three cell lines to DFUR. We report for the first time a nucleobase transport activity in hRPTCs and RCC cell lines. In addition, our in vitro cytotoxicity results showed that RCC cell lines differed in their response to 5 FU and DFUR and prior treatment with IFN-alpha potentiated cytotoxic response to metabolites of capecitabine. PMID- 24219282 TI - p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion. AB - Arachidonic acid stimulates cell adhesion by activating alpha2beta1 integrins in a process that depends on protein kinases, including p38 mitogen activated protein kinase. Here, we describe the interaction of cytoskeletal components with key signaling molecules that contribute to the spreading of, and morphological changes in, arachidonic acid-treated MDA-MB-435 human breast carcinoma cells. Arachidonic acid-treated cells showed increased attachment and spreading on collagen type IV, as measured by electric cell-substrate impedance sensing. Fatty acid-treated cells displayed short cortical actin filaments associated with an increased number of beta1 integrin-containing pseudopodia, whereas untreated cells displayed elongated stress fibers and fewer clusters of beta1 integrins. Confocal microscopy of arachidonic acid-treated cells showed that vinculin and phospho-p38 both appeared enriched in pseudopodia and at the tips of actin filaments, and fluorescence ratio imaging indicated the increase was specific for the phospho-(active) form of p38. Immunoprecipitates of phospho-p38 from extracts of arachidonic acid-treated cells contained vinculin, and GST-vinculin fusion proteins carrying the central region of vinculin bound phospho-p38, whereas fusion proteins expressing the terminal portions of vinculin did not. These data suggest that phospho-p38 associates with particular domains on critical focal adhesion proteins that are involved in tumor cell adhesion and spreading, and that this association can be regulated by factors in the tumor microenvironment. PMID- 24219284 TI - Activation of nucleotide oligomerization domain containing protein 1 induces lipolysis through NF-kappaB and the lipolytic PKA activation in 3T3-L1 adipocytes. AB - Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like receptors (NLR) are two families of pattern recognition receptors that play important roles in the immune response and inflammation in adipocytes. Activation of TLR4 has been shown to stimulate lipolysis from adipose tissue or adipocytes. However, effects of activation of nucleotide-oligomerization domain containing protein 1 (NOD1), one of the prominent members of NLRs, on adipocyte lipolysis have not been studied. Here we report that NOD1 activation by the synthetic ligands (Tri-DAP and C12-iEDAP) stimulated lipolysis in 3T3-L1 adipocytes in a time- and dose-dependent manner. C12-iEDAP-induced lipolysis was attenuated with NOD1 siRNA knockdown, demonstrating the specificity of the effects. Moreover, inhibition of the protein kinase A (PKA)/hormone sensitive lipase (HSL) and NF-kappaB pathways by the pharmacological inhibitors attenuated the lipolytic effects of C12-iEDAP. Furthermore, we show NOD1 activation induced PKA activation independent of cAMP production and inhibition of NF-kappaB pathways attenuated phosphorylation of selected PKA lipolytic targets (phosphorylation of Perilipin Ser 517 and HSL Ser 563). Taken together, our results demonstrate a novel role of NOD1 activation, via NF-kappaB/PKA lipolytic activation, in inducing lipolysis in adipocytes and suggest that NOD1 activation may contribute to dyslipidemia in obesity. PMID- 24219285 TI - Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts. AB - Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease. PMID- 24219286 TI - Elevation of protein kinase Calpha stimulates osteogenic differentiation of mesenchymal stem cells through the TAT-mediated protein transduction system. AB - Mesenchymal stem cells (MSCs) can differentiate toward various lineages, including the osteogenic lineage, and thus hold great potential for clinic purposes. By using pharmacological inhibitors, protein kinase C (PKC) signaling has been shown to either negatively or positively regulate differentiation of bone, however, due to the low transfection efficiency in MSCs, the role of individual PKC isoforms is still not fully understood. In this study, we established a TAT peptide-mediated transduction system that efficiently delivered PKCalpha proteins into MSCs in a non-invasive fashion. The increased PKCalpha protein levels significantly promoted osteogenic differentiation in the murine mesenchymal C3H10T1/2 cells and in primary MSCs from both human and mouse, as demonstrated by the enhanced activity of the osteoblast marker, alkaline phosphatase, and the enhanced expression of the key transcription factor runx2. Mineralization is an important functional indication for bone differentiation. Our results further showed that PKCalpha promoted expression of the important osteocalcin gene and the accumulation of calcium minerals. Taken together, this study provides direct evidence showing that PKCalpha positively regulates osteogenic differentiation and demonstrates that the TAT peptide-mediated method enables functional study of specific PKC isoforms in MSCs without using viral infection. This may promote the application of PKCs in therapeutic treatment. PMID- 24219287 TI - Proteolytic antigens interfere with endosome/lysosome fusion in epithelial cells. AB - The airway epithelial barrier function is important in maintaining the homeostasis in the body. A number of airway disorders are associated with the epithelial barrier dysfunction. The present study aims to elucidate a possible mechanism by which the proteolytic allergens compromise the epithelial barrier function. The airway epithelial cell line, RPMI 2650 cells (Rp cells) and kidney epithelial cell line, MDCK cells, were cultured to be monolayers and used as an in vitro epithelial barrier model. House dust mite antigen, Der P1 (Der) was used as an antigen that has the proteolytic property. The epithelial barrier permeability and transepithelial resistance (TER) were used as the indicators of epithelial barrier function. Both epithelial cell lines could endocytose Der in the culture. Some of the Der was transported across the epithelial barrier to the basal chambers of the Transwells without affecting the TER. The endocytic Der could suppress the expression of ubiquitin E3 lases A20 and further interfered with the fusion of endosome/lysosome in the epithelial cells. Mite antigen, Der, can interfere with the fusion of endosome/lysosome in epithelial cells to induce the epithelial barrier dysfunction. PMID- 24219288 TI - Vps1, a recycling factor for the traffic from early endosome to the late Golgi. AB - Recycling of cellular membranes and their constituents plays a role for cell survival and growth. In the budding yeast, there are recycling traffics from early and late endosomal compartments to the late Golgi. Here, we examined a possible role for Vps1, a large GTPase, in the recycling traffic of GFP-Snc1 from early endosomes to the late Golgi. In the absence of Vps1 we observed an aberrant accumulation of GFP-Snc1 puncta in the cytoplasm that we identified as early endosomes. The N-terminal GTPase and the C-terminal GED domains of Vps1 are essential for Vps1's function in Snc1 recycling. Our finding of genetic interactions of VPS1 with genes involved in early endosome-to-Golgi traffic further suggests Vps1 functions as a recycling factor in the membrane traffic. Finally, we provide evidence that the severe accumulation of GFP-Snc1 cytoplasmic puncta in vps1Delta cells is attributed to a mild defect in the retention of the GARP component Vps51 at the late Golgi, as well as a severe disruption of actin cables. PMID- 24219289 TI - Interaction, mobility, and phosphorylation of human orthologues of WD repeat containing components of the yeast SSU processome t-UTP sub-complex. AB - We previously proposed a dynamic scaffold model for inner nuclear structure formation. In this model, structures in inter-chromatin regions are maintained through dynamic interaction of protein complex modules, and WD repeat- and disordered region-rich proteins and others act as scaffolds for these protein complexes. In this study, three WD-repeat proteins, i.e., CIRH1A, UTP15, and WDR43, were found in the nuclear matrix fraction and speculated to be present in the human t-UTP sub-complex of SSU processomes. The results obtained as to their subnuclear localization, binding with each other, mobilities, and phosphorylation were: (i) the majority of these proteins fused with GFP are localized to the fibrillar center region in nucleoli. (ii) these 3 proteins bind directly with each other in vitro. (iii) the movement of these proteins is very slow in living cells and independent of rDNA transcription. (iv) His-CIRH1A is phosphorylated at Thr(131) by a mitotic Xenopus egg extract, and binding with GST-UTP15 and GST WDR43 is suppressed. These findings and others suggest that these 3 WD proteins found in the matrix fraction bind directly with each other, bind tightly to fibrillar center regions, and comprise a part of the nucleolar structure. These results are also consistent with our dynamic scaffold model. PMID- 24219290 TI - Role of the apical and basolateral domains of the enterocyte in the regulation of cholesterol transport by a high glucose concentration. AB - We have recently shown that a high glucose (HG) concentration raised intestinal cholesterol (CHOL) transport and metabolism in intestinal epithelial cells. The objective of the present work is to determine whether the stimulus for increased CHOL absorption by glucose originates from the apical site (corresponding to the intestinal lumen) or from the basolateral site (related to blood circulation). We tackled this issue by using differentiated Caco-2/15 cells. Only basolateral medium, supplemented with 25 mmol/L glucose, stimulated [(14)C]-CHOL uptake via the up-regulation of the critical CHOL transporter NPC1L1 protein, as confirmed by its specific ezetimibe inhibitor that abolished the rise in glucose-mediated CHOL capture. No significant changes were noted in SR-BI and CD36. Elevated CHOL uptake was associated with an increase in the transcription factors SREBP-2, LXR beta, and ChREBP, along with a fall in RXR-alpha. Interestingly, although the HG concentration in the apical medium caused modest changes in CHOL processing, its impact was synergetic with that of the basolateral medium. Our results suggest that HG concentration influences positively intestinal CHOL uptake when present in the basolateral medium. In addition, excessive consumption of diets containing high levels of carbohydrates may strengthen intestinal CHOL uptake in metabolic syndrome, thereby contributing to elevated levels of circulating CHOL and, consequently, the risk of developing type 2 diabetes and cardiovascular disease. PMID- 24219291 TI - Implantation serine proteinase 2 is a monomeric enzyme with mixed serine proteolytic activity and can silence signalling via proteinase activated receptors. AB - Implantation serine proteinase 2 (ISP2), a S1 family serine proteinase, is known for its role in the critical processes of embryo hatching and implantation in the mouse uterus. Native implantation serine proteinases (ISPs) are co-expressed and co-exist as heterodimers in uterine and blastocyst tissues. The ISP1-ISP2 enzyme complex shows trypsin-like substrate specificity. In contrast, we found that ISP2, isolated as a 34 kDa monomer from a Pichia pastoris expression system, exhibited a mixed serine proteolytic substrate specificity, as determined by a phage display peptide cleavage approach and verified by the in vitro cleavage of synthetic peptides. Based upon the peptide sequence substrate selectivity, a database search identified many potential ISP2 targets of physiological relevance, including the proteinase activated receptor 2 (PAR2). The in vitro cleavage studies with PAR2-derived peptides confirmed the mixed substrate specificity of ISP2. Treatment of cell lines expressing proteinase-activated receptors (PARs) 1, 2, and 4 with ISP2 prevented receptor activation by either thrombin (PARs 1 and 4) or trypsin (PAR2). The disarming and silencing of PARs by ISP2 may play a role in successful embryo implantation. PMID- 24219292 TI - 15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway. AB - Chronic low-grade inflammation underlies obesity and associated metabolic dysfunctions. Lipoxygenase pathways are activated in adipose tissue during obese conditions. Since adipogenesis is associated with angiogenesis, the present study was designed to examine the role of 15-lipoxygenase metabolite, 15(S) hydroxyeicosatetraenoic acid [15(S)-HETE] on angiogenesis in adipose tissue. Results showed that 15(S)-HETE induced sprouting in fat pad stromovascular tissues, induced morphological changes relevant to angiogenesis in endothelial cells derived from adipose tissue, upregulated the production of CD31, upregulated the gene level expression and production of vascular endothelial growth factor (VEGF), indicating the pro-angiogenic effect of 15(S)-HETE. LY294002, an inhibitor of PI3K-Akt pathway, and rapamycin, inhibitor of mammalian target of rapamycin (mTOR), significantly reversed the effect of 15(S)-HETE. 15(S)-HETE also induced activation of Akt and mTOR. These observations suggest that 15(S)-HETE stimulates angiogenesis in adipose tissue through activation of PI3K/Akt/mTOR signaling. PMID- 24219293 TI - Intron retention: a human DKC1 gene common splicing event. AB - Identification of alternatively spliced transcripts produced by a gene is a crucial step in deciphering the bulk of its biological roles and the overall processes that regulate its activity. By using a combination of bioinformatic and molecular approaches we identified, cloned, and characterized 3 novel alternative splice isoforms derived from human dyskeratosis congenita 1 (hDKC1), an essential human gene causative of the X-linked dyskeratosis congenita disease and involved in multiple functions related to cell growth, proliferation, and telomere maintenance. Expression of the new isoforms, all characterized by intron retention, was confirmed by RT-PCR in a panel of diverse cell lines and normal human tissues, and despite the presence of premature termination codons, was not down-regulated by the mechanism of nonsense-mediated decay. Accumulation of these transcripts fluctuated distinctly in the diverse tissues and during in vitro differentiation of Caco2 cells, suggesting that their ratio may contribute to the gene functional diversity across different cell types. Intriguingly, the structure of one isoform leads to exonize an intronically encoded small nucleolar RNA (snoRNA), highlighting an additional layer of complexity that can contribute to overall gene regulation. PMID- 24219294 TI - A combination of insulin and ubiquitin A20 promotes osteocalcin expression in adipose-derived stem cells. AB - Osteocyte generation can be used in bone defect repair; the generation efficiency needs to be further improved. This study aims to evaluate the role of ubiquitin A20 (A20) in facilitating the expression of osteocalcin in adipose-derived stem cells (ADSCs). In this study, adipose tissue was obtained from 10 healthy human subjects; ADSCs were isolated from the adipose samples. The ADSCs were transfected with core binding factor alpha 1 (Cbfa1) and/or insulin-like growth factor-1 receptor (IGF-1R). Expression of osteocalcin, A20 in ADSCs was assessed by quantitative RT-PCR (qRT-PCR) and Western blotting. Apoptosis of ADSCs was analyzed by flow cytometry. The results showed that after the gene transfection and stimulation of insulin, the ADSCs expressed high levels of osteocalcin. However, apoptotic ADSCs were induced by the activation of IGF-1R. Exposure to insulin down-regulated the expression of Bcl-xL and A20, and increased Bax, in ADSCs. The addition of exogenous A20 prevented the ADSC apoptosis. We conclude that activation of IGF-1R can induce apoptosis in ADSCs, which can be prevented by addition of exogenous A20. PMID- 24219295 TI - Dramatic differences in activity of purines metabolizing ecto-enzymes between mesenchymal stem cells isolated from human umbilical cord blood and umbilical cord tissue. AB - The high quality human mesenchymal stem cells (MSCs) with remarkable expansion potential in culture are demonstrated to possess multifold clinical applications. However, their isolation and characterization are difficult and sometimes ambiguous. We exploited nucleotide metabolizing ecto-enzymes for more complete characterization of MSCs. Using standard methods of cell culturing and analyses, we detected significant differences in the activity of ecto-nucleotidases on the surface of MSCs isolated from umbilical cord tissue and MSC-like cells derived from umbilical cord blood. Interestingly, the proliferation rate and the immunophenotypic characteristics of mesenchymal stem cells also correspond to the activities of these enzymes. Compared with the CD90-, CD105-, and CD73-deficient and slowly proliferating UCB-MSC-like cells that had relatively higher ecto NTPDases activity, the CD90-, CD105-, and CD73-positive and rapidly proliferating UC-MSCs rather had ecto-5'-nucleotidase activity and presented neither ecto nucleotidases nor adenylate kinase activities. In summary, our results demonstrate for the first time that activity of purine nucleotide metabolizing ecto-enzymes differs significantly between mesenchymal stem cells drawn from different neonatal sources, corresponding with a distinct proliferative potential. PMID- 24219296 TI - Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo. AB - Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells. PMID- 24219298 TI - Characterization of the T-dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) in the Gottingen minipig. AB - Recently, there has been a renewed interest in the use of the minipig as an alternative to dogs and non-human primates for conducting toxicological assessments in non-rodent species. Since the T-dependent antibody response (TDAR) is one of the most widely-accepted assays used in the assessment of immunocompetence, the present study was undertaken to characterize the primary and secondary TDAR to keyhole limpet hemocyanin (KLH) in the Gottingen Minipig((r)). Following primary immunization with either 2 or 10 mg KLH, anti swine IgM and IgG ELISAs were optimized and individual animal responses were evaluated over time. Immunization with 10 mg KLH on Day 0 promoted primary IgM responses that peaked 6-9 days after antigen administration, while primary IgG levels peaked on Day 13 or 14. Secondary IgG antibody levels (following secondary injection with 2 mg KLH on Day 14) plateaued on Days 20-22. Anti-KLH antibody levels were decreased in minipigs treated with cyclophosphamide (CPS), a known immunosuppressant, at doses ranging from 12.5-50 mg/kg/day, while antibody levels in animals treated with 2.5 mg CPS/kg/day were similar to levels in saline treated swine. These results demonstrate that the Gottingen Minipig((r)) can be a useful alternative non-rodent species to the dog and the non-human primate for evaluating the TDAR to KLH in regulatory assessments of immunotoxicity. PMID- 24219299 TI - Characterization of two passive air samplers for per- and polyfluoroalkyl substances. AB - Two passive air sampler (PAS) media were characterized under field conditions for the measurement of per- and polyfluoroalkyl substances (PFASs) in the atmosphere. The PASs, consisting of polyurethane foam (PUF) and sorbent-impregnated PUF (SIP) disks, were deployed for over one year in parallel with high volume active air samplers (HV-AAS) and low volume active air samplers (LV-AAS). Samples were analyzed for perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkane sulfonic acids (PFSAs), fluorotelomer alcohols (FTOHs), fluorotelomer methacrylates (FTMACs), fluorotelomer acrylates (FTACs), perfluorooctane sulfonamides (FOSAs), and perfluorooctane sulfonamidoethanols (FOSEs). Sampling rates and the passive sampler medium (PSM)-air partition coefficient (KPSM-A) were calculated for individual PFASs. Sampling rates were similar for PFASs present in the gas phase and particle phase, and the linear sampling rate of 4 m(-3) d(-1) is recommended for calculating effective air sample volumes in the SIP-PAS and PUF-PAS for PFASs except for the FOSAs and FOSEs in the PUF-PAS. SIP disks showed very good performance for all tested PFASs while PUF disks were suitable only for the PFSAs and their precursors. Experiments evaluating the suitability of different isotopically labeled fluorinated depuration compounds (DCs) revealed that (13)C8 perfluorooctanoic acid (PFOA) was suitable for the calculation of site-specific sampling rates. Ambient temperature was the dominant factor influencing the seasonal trend of PFASs. PMID- 24219301 TI - A system to help physicians with fracture detection in stents. AB - Fractures in stents are usually detected by visual analysis, which may be affected by the presence of noise and image deformations. The lack of research into automating stent fracture detection has motivated this work, in which techniques are developed to facilitate diagnosis by observation (Image Delineation Algorithm) and, when possible, to point out areas of possible fractures (Fracture Detection Algorithm). The use of classical elements and the development of additional computational techniques contributed to the process of image analysis, providing a possible way to aid medical diagnosis. The developed algorithms are applied to image samples from femoropopliteal arteries, and the results are compared to those of medical diagnosis. As a result, aside from the improvement of image display, a kappa concordance index of 0.878 for the detection of fractures confirms the method as satisfactory, with very good agreement with medical diagnosis. PMID- 24219300 TI - ALSUntangled no. 23: the Rife machine and retroviruses. PMID- 24219302 TI - Reduced comparison speed during visual search in late life depression. AB - Slowed information processing is a prominent deficit in late-life depression (LLD). To better differentiate processing speed components in LLD, we examined characteristics of visual search performance in 32 LLD and 32 control participants. Data showed specific slowing in the comparison stage of visual search in LLD, rather than in encoding/response stages, but also greater overall slowing in LLD during inefficient versus efficient search. We found no group differences on traditional neuropsychological measures of processing speed. Slowed processing speed in LLD may be specific rather than general, which underscores the need to link components of processing speed to underlying neural circuitry. PMID- 24219303 TI - Evaluating adverse drug event reporting in administrative data from emergency departments: a validation study. AB - BACKGROUND: Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data. METHODS: We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data. RESULTS: Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0-11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%). CONCLUSIONS: Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care. PMID- 24219304 TI - Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice. AB - Drinking in the dark (DID) is a limited access ethanol-drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h(2) = 0.09) but the lines have shown 4-5 fold increases in BEC since S0; 80% of HDID-1 and 60% of HDID-2 mice reach BECs greater than 1.0 mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID-1 and 60% in HDID-2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2 h of the 4 h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol. PMID- 24219305 TI - Density functional theory calculations in stereochemical determination of terpecurcumins J-W, cytotoxic terpene-conjugated curcuminoids from Curcuma longa L. AB - Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J-W (1-14), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J Q and V represent four unprecedented skeletons featuring an unusual core of hydrobenzannulated[6,6]-spiroketal (1 and 2), bicyclo[2.2.2]octene (3-7), bicyclo[3.1.3]octene (8), and spiroepoxide (13), respectively. The structures of compounds 1-14 were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and (13)C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of 1 was further confirmed by single-crystal X-ray diffraction (Cu Kalpha). The biogenetic pathways of 1-14 were proposed, involving Michael addition, condensation, Diels-Alder cycloaddition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/beta-turmerone. Among them, terpecurcumin Q (8) exhibited IC50 of 3.9 MUM against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level. PMID- 24219306 TI - Academic self-concept of ability and cortisol reactivity. AB - The present study aimed to clarify the relationship between a school-specific trait (academic self-concept of ability [ASCA]) and hormonal stress response by using a trait-compatible stressor (test). First, we determined 52 students' ASCA scores for biology and measured their salivary cortisol concentration before and after a biology test (experimental group, n=28) or a free writing task (control group, n=24). For participants who took the test, statistical analysis indicated a significant negative correlation between ASCA score and cortisol response. In contrast, the control group showed a decrease in cortisol concentrations between test times and no correlation between cortisol concentration and ASCA scores were found. These findings indicated an interaction between ASCA scores and hormonal stress response when an academic-related stressor is present. Furthermore, these variables might influence each other adversely: high cortisol concentrations during a test situation may lead to greater feelings of insecurity, resulting in low ASCA scores and awareness of these low scores may lead to a further increase in cortisol, creating a vicious cycle. PMID- 24219307 TI - Accessory mitral valve--an unexpected intra-operative TEE finding causing left ventricular outflow tract obstruction in an adult. AB - There is a long-standing debate between proponents of routine intra-operative echo and those who want it restricted to selected groups of patients (such as those undergoing valve repair or correction of congenital abnormalities). We present a case where routine transesophageal echocardiography (TEE) identified completely unexpected pathology, with implications for the postoperative follow up and for patient outcomes. A 64-year-old male, with a history of surgical repair of coarctation of the aorta in childhood, was admitted for elective valve replacement for severe aortic stenosis (AS). Previous transthoracic echocardiography had not identified any other pathology apart from AS, but routine intra-operative TEE picked up severe turbulence in the left ventricular outflow tract (LVOT). On further analysis this was due to 2 mechanisms: a localized subaortic membrane and a "cystic" mass attached to the anterior mitral leaflet, protruding into the LVOT in systole. Multiplane imaging of the mass disclosed an accessory mitral valve (MV), a rare congenital abnormality. The patient had excision of the stenosed aortic valve and of the subaortic membrane, while the accessory MV was spared, as the surgeon judged its removal might distort the mitral apparatus. Postoperative recovery was unremarkable and the patient went home with symptomatic improvement. This case illustrates the fact that even "standard" cardiac procedures can benefit from intra-operative TEE which, in our view, should be available for all patients who undergo heart surgery. PMID- 24219309 TI - Duodenal metastasis from subcutaneous angiosarcoma of the head: rare cause of obscure gastrointestinal bleeding. PMID- 24219308 TI - Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue. AB - Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium. PMID- 24219311 TI - Potential use of the complex of doxorubicin with folate-conjugated methyl-beta cyclodextrin for tumor-selective cancer chemotherapy. AB - Abstract In a recent study, we attempted to confer a tumor-selective cytotoxic activity to methyl-beta-cyclodextrin (M-beta-CyD), we synthesized folate conjugated M-beta-CyD (FA-M-beta-CyD), and demonstrated the potential of FA-M beta-CyD as a novel anticancer agent at a high dose. In the present study, to expand the application of FA-M-beta-CyD for cancer chemotherapy, we evaluated the potential of FA-M-beta-CyD as a tumor-targeting anticancer drug carrier at a low dose. FA-M-beta-CyD formed an inclusion complex with doxorubicin (DOX) with a high-stability constant (3.0 * 105 M-1). Antitumor activity of DOX was increased by the complexation with FA-M-beta-CyD, but not with folate-conjugated beta-CyD (FA-beta-CyD) or M-beta-CyD in KB cells, a folate receptor-alpha (FR-alpha) expressing cell line. Also, FA-M-beta-CyD increased antitumor activity of paclitaxel, a class IV compound in the biopharmaceutical classification system (BCS), but not 5-fluorouracil, a class III compound in the BCS. Furthermore, FA-M beta-CyD enhanced cellular uptake of DOX through a complexation in KB cells (FR alpha (+)), compared to FA-beta-CyD and M-beta-CyD. The DOX/FA-M-beta-CyD complex showed markedly high antitumor activity, compared to DOX alone and DOX/M-beta-CyD complex, after an intravenous administration to FR-alpha-expressing tumor cell bearing mice. These findings suggest that FA-M-beta-CyD could be useful as a tumor-selective carrier for anticancer drugs. PMID- 24219310 TI - Comparison between ultrasonographic and clinical findings in 43 dogs with gallbladder mucoceles. AB - Cholecystectomy is the current standard recommended treatment for dogs with gallbladder mucoceles. However, medical management with monitoring has also been recommended for asymptomatic dogs. The purpose of this retrospective study was to compare ultrasonographic patterns of gallbladder mucoceles with clinical disease status in a group of dogs. For each included dog, the ultrasonographic pattern of the mucocele was classified into one of six types: type 1, immobile echogenic bile; type 2, incomplete stellate pattern; type 3, typical stellate pattern; type 4, kiwi like pattern and stellate combination; type 5, kiwi like pattern with residual central echogenic bile; and type 6, kiwi like pattern. A total of 43 dogs were included. Twenty-four dogs, including 11 dogs with gallbladder rupture, were symptomatic. Nineteen dogs were asymptomatic. Cholecystectomy (n = 19), medical therapy (n = 17), or monitoring (n = 6) treatments were applied according to clinical signs and owners' requests. One dog suspected of having gallbladder rupture was euthanized. Frequencies of gallbladder mucocele patterns were as follows: type 1 = 10 (23%), type 2 = 13 (30%), type 3 = 5 (12%), type 4 = 11 (26%), type 5 = 4 (9%), and type 6 = 0. In dogs with gallbladder rupture, type 2 (8/13) was the most common. No significant correlations were found between ultrasonographic patterns of gallbladder mucoceles and clinical disease status or gallbladder rupture. Findings indicated that ultrasonographic patterns of gallbladder mucoceles may not be valid bases for treatment recommendations in dogs. PMID- 24219312 TI - Diagnostic performance and inter-observer concordance in lesion detection with the automated breast volume scanner (ABVS). AB - BACKGROUND: Automated whole breast ultrasound scanners of the latest generation have reached a level of comfortable application and high quality volume acquisition. Nevertheless, there is a lack of data concerning this technology. We investigated the diagnostic performance and inter-observer concordance of the Automated Breast Volume Scanner (ABVS) ACUSON S2000TM and questioned its implications in breast cancer diagnostics. METHODS: We collected 100 volume data sets and created a database containing 52 scans with no detectable lesions in conventional ultrasound (BI-RADS(r)-US 1), 30 scans with benign lesions (BI RADS(r)-US 2) and 18 scans with breast cancer (BI-RADS(r)-US 5).Two independent examiners evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. RESULTS: The inter-rater reliability reached fair agreement (kappa=0.36; 95% confidence interval (CI): 0.19-0.53). With respect to the true category, the conditional inter-rater validity coefficient was kappa=0.18 (95% CI: 0.00-0.26) for the benign cases and kappa=0.80 (95% CI: 0.61-1.00) for the malignant cases.Combining the assessments of examiner 1 and examiner 2, the diagnostic accuracy (AC), sensitivity (SE) and specificity (SP) for the experimental ABVS were AC = 79.0% (95% CI: 67.3-86.1), SE = 83.3% (95% CI: 57.7-95.6) and SP = 78.1% (% CI: 67.3-86.1), respectively.However, after the ABVS examination, there were a high number of requests for second-look ultrasounds in up to 48.8% of the healthy women due to assumed suspicious findings in the volume data.In an exploratory analysis, we estimated that an ABVS examination in addition to mammography alone could detect a relevant number of previously occult breast cancers (about 1 cancer in 300 screened and otherwise healthy women). CONCLUSIONS: The ABVS is a reliable imaging method for the evaluation of the breast with high sensitivity and a fair inter-observer concordance. However, we have to overcome the problem of the high number of false-positive results. Therefore, further prospective studies in larger collectives are necessary to define standard procedures in image acquisition and interpretation. Nevertheless, we consider the ABVS as being suitable for integration into breast diagnostics as a beneficial and reliable imaging method. PMID- 24219314 TI - The malleability of working memory and visuospatial skills: a randomized controlled study in older adults. AB - There is accumulating evidence that training on working memory (WM) generalizes to other nontrained domains, and there are reports of transfer effects extending as far as to measures of fluid intelligence. Although there have been several demonstrations of such transfer effects in young adults and children, they have been difficult to demonstrate in older adults. In this study, we investigated the generalizing effects of an adaptive WM intervention on nontrained measures of WM and visuospatial skills. We randomly assigned healthy older adults to train on a verbal n-back task over the course of a month for either 10 or 20 sessions. Their performance change was compared with that of a control group. Our results revealed reliable group effects in nontrained standard clinical measures of WM and visuospatial skills in that both training groups outperformed the control group. We also observed a dose-response effect, that is, a positive relationship between training frequency and the gain in visuospatial skills; this finding was further confirmed by a positive correlation between training improvement and transfer. The improvements in visuospatial skills emerged even though the intervention was restricted to the verbal domain. Our work has important implications in that our data provide further evidence for plasticity of cognitive functions in old age. PMID- 24219313 TI - beta-Lactamase inhibition by 7-alkylidenecephalosporin sulfones: allylic transposition and formation of an unprecedented stabilized acyl-enzyme. AB - The inhibition of the class A SHV-1 beta-lactamase by 7-(tert butoxycarbonyl)methylidenecephalosporin sulfone was examined kinetically, spectroscopically, and crystallographically. An 1.14 A X-ray crystal structure shows that the stable acyl-enzyme, which incorporates an eight-membered ring, is a covalent derivative of Ser70 linked to the 7-carboxy group of 2-H-5,8-dihydro 1,1-dioxo-1,5-thiazocine-4,7-dicarboxylic acid. A cephalosporin-derived enzyme complex of this type is unprecedented, and the rearrangement leading to its formation may offer new possibilities for inhibitor design. The observed acyl enzyme derives its stability from the resonance stabilization conveyed by the beta-aminoacrylate (i.e., vinylogous urethane) functionality as there is relatively little interaction of the eight-membered ring with active site residues. Two mechanistic schemes are proposed, differing in whether, subsequent to acylation of the active site serine and opening of the beta-lactam, the resultant dihydrothiazine fragments on its own or is assisted by an adjacent nucleophilic atom, in the form of the carbonyl oxygen of the C7 tert butyloxycarbonyl group. This compound was also found to be a submicromolar inhibitor of the class C ADC-7 and PDC-3 beta-lactamases. PMID- 24219315 TI - The longitudinal interplay of affective and cognitive empathy within and between adolescents and mothers. AB - This 4-year study examined longitudinal interplays between adolescents' and mothers' self-reported empathic concern (EC) and perspective taking (PT). We investigated (a) whether adolescents' EC predicted rank-order change in their PT over time, or vice versa; (b) whether mothers' empathy predicted relative increases in adolescents' empathy; (c) whether adolescent gender moderated the over-time links from mothers' to adolescents' empathy; and (d) whether the rank order stability of EC and PT over time differed within and between respondents. Adolescents' EC positively predicted their PT over time, but not vice versa. Mothers' PT positively predicted adolescent PT over time for girls, but not for boys. The rank-order stability of adolescents' EC was greater than their PT. Maternal PT and EC were equally stable and were more stable than in adolescents. This study contributes the first empirical evidence that the developmental order of adolescents' empathy runs from affective to cognitive empathy, in contrast to prior theoretical and experimental literature that has emphasized the reverse direction. It further provides the 1st longitudinal evidence of intergenerational empathy transmission. These findings support the notion that adolescence is a developmentally sensitive period for PT. PMID- 24219316 TI - Mother-child reminiscing and autobiographical memory specificity among preschool age children. AB - Overgeneral memory (OGM) refers to difficulty in retrieving specific autobiographical memories. The tendency to be overgeneral in autobiographical memory recall is more commonly observed among individuals with emotional disorders compared with those without. Despite significant advances in theory and identification of mechanisms that underlie the etiology of OGM, there has been little integration between normative research on the development of autobiographical memory and research on OGM. Informed by a developmental psychopathology perspective and drawing on normative developmental research on the social construction of autobiographical memory, the current investigation examined whether the elaborative quantity and elaborative quality of maternal reminiscing are predictive of preschool-age children's autobiographical memory specificity. Additionally, this investigation tested whether children's positive self-representations may explain these hypothesized associations. Participants consisted of 95 mother-child dyads. Children's ages ranged between 3.5 and 6 years, and the sample was predominantly low income and of minority race/ethnicity. Dyads participated in a joint reminiscing task about 4 past events, and children participated in assessments of autobiographical memory specificity and self-representations. Results indicated that the elaborative quality, defined by maternal-sensitive guidance and emotional narrative coherence, but not the elaborative quantity, of maternal reminiscing style was significantly associated with children's autobiographical memory specificity. Additionally, there was support for an indirect pathway between maternal reminiscing quality and child memory specificity through children's positive self representations. Directions for future research are discussed, and potential clinical implications are addressed. PMID- 24219317 TI - Preference for high status predicts implicit outgroup bias among children from low-status groups. AB - Whereas members of high-status racial groups show ingroup preference when attitudes are measured implicitly, members of low-status racial groups--both adults and children--typically show no bias, potentially reflecting awareness of the ingroup's low status. We hypothesized that when status differences are especially pronounced, children from low-status groups would show an implicit outgroup bias, the strength of which might relate to attitudes toward status. We tested these predictions among 6- to 11-year-old Black and Coloured (i.e., multiracial) children from South Africa, a country marked by extreme status differentials among racial groups. As a measure of implicit intergroup bias, children (N = 78) completed an Implicit Association Test (IAT), a speeded categorization task that assesses the relative strength of association between 2 target groups (in the present study, either Whites vs. Blacks or Whites vs. Coloureds) and positive vs. negative evaluation. Children also completed explicit (i.e., self-report) measures of attitudes toward racial groups as well as toward rich and poor people (a measure of attitudes toward status). Both groups of children showed an implicit outgroup-favoring (i.e., pro-White) bias, suggesting that children were sensitive to the extent of status differences. The only instance in which implicit pro-White bias did not emerge involved Black children's evaluations of Whites vs. Coloureds, both higher-status outgroups. Explicit preference for high status predicted implicit pro-White bias, particularly when the IAT contrasted 2 outgroups. The impact of status on the development of implicit and explicit intergroup bias is discussed. PMID- 24219318 TI - Maternal immunization with vaccines containing recombinant NetB toxin partially protects progeny chickens from necrotic enteritis. AB - Avian necrotic enteritis is a major economic and welfare issue throughout the global poultry industry and is caused by isolates of Clostridium perfringens that produce NetB toxin. Previously we have shown that birds directly vaccinated with inactivated C. perfringens type A culture supernatant (toxoid) combined with recombinant NetB (rNetB) protein were significantly protected from homologous and heterologous challenge. In the present study the protective effect of maternal immunization was examined. Broiler breeder hens were injected subcutaneously with genetically toxoided rNetB(S254L) alone, C. perfringens type A toxoid and toxoid combined with rNetB(S254L). Vaccination resulted in a strong serum immunoglobulin Y response to NetB in hens immunized with rNetB(S254L) formulations. Anti-NetB antibodies were transferred to the eggs and on into the hatched progeny. Subclinical necrotic enteritis was induced experimentally in the progeny and the occurrence of specific necrotic enteritis lesions evaluated. Birds derived from hens immunized with rNetB(S254L) combined with toxoid and challenged with a homologous strain (EHE-NE18) at either 14 or 21 days post-hatch had significantly lower levels of disease compared to birds from adjuvant only vaccinated hens. In addition, birds from hens immunized with rNetB(S254L) alone were significantly protected when challenged at 14 days post-hatch. These results demonstrate that maternal immunization with a NetB-enhanced toxoid vaccine is a promising method for the control of necrotic enteritis in young broiler chickens. PMID- 24219319 TI - An intensive time-series evaluation of the effectiveness of cognitive behaviour therapy for hoarding disorder: a 2-year prospective study. AB - OBJECTIVE: To intensively evaluate the effectiveness of cognitive-behavioural therapy (CBT) for Hoarding Disorder. METHOD: An ABC with extended follow-up N=1 single-case experimental design (SCED) measured discard incidence/frequency/volume and associated cognitions, behaviours and emotions in a 644-day time series. Following a 4-week baseline (A), CBT was initially delivered via out-patient sessions (B) and then out-patient sessions plus domiciliary visits (C). Total treatment duration was 45 sessions (65 weeks) and follow-up was 4 sessions over 23 weeks. RESULTS: There was a significant increase in frequency and volume of discard, with a reliable and clinically significant reduction in hoarding. The addition of domiciliary visits did not significantly improve discard ability. DISCUSSION: The clinical utility of domiciliary visits whilst treating of hoarding is discussed and study limitations noted. PMID- 24219320 TI - The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross talk, and therapies. AB - Head and neck squamous cell carcinoma (HNSCC) is one of the most morbid, mortal, and genetically diverse malignancies. Although HNSCC is heterogeneous in nature, alterations in major components of the PI3K/Akt/mTOR pathway are consistently observed throughout the majority of HNSCC cases. These alterations include genetic aberrations, such as mutations or DNA copy number variations, and dysregulation of mRNA or protein expression. In normal physiology, the PI3K/Akt/mTOR axis regulates cell survival, growth, and metabolism. However, alterations in this pathway lead to the malignant phenotype which characterizes HNSCC, among many other cancers. For this reason, both pharmaceutical companies and academic institutions are actively developing and investigating inhibitors of PI3K, Akt, and mTOR in preclinical and clinical studies of HNSCC. Many of these inhibitors have shown promise, while the effects of others are tempered by the mechanisms through which HNSCC can evade therapy. As such, current research aimed at elucidating the interactions between PI3K/Akt/mTOR and other important signaling pathways which may drive resistance in HNSCC, such as p53, NF-kappaB, and MAPK, has become a prominent focus toward better understanding how to most effectively treat HNSCC. PMID- 24219322 TI - Construction of targeting-clickable and tumor-cleavable polyurethane nanomicelles for multifunctional intracellular drug delivery. AB - New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a novel targeting-clickable and tumor cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(epsilon caprolactone) (PCL) and L-lysine ethyl ester diisocyanate (LDI), further extended by a new designed L-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery. PMID- 24219321 TI - Fibroblasts from long-lived species of mammals and birds show delayed, but prolonged, phosphorylation of ERK. AB - Fibroblasts from long-lived mutant mice show diminished phosphorylation of the stress-activated protein kinases ERK1/2 after exposure to peroxide, cadmium, or paraquat. We have now evaluated the kinetics of ERK phosphorylation in fibroblasts from long-lived and short-lived species of mammals and birds in response to stress by cadmium or hydrogen peroxide. Fibroblasts from the shorter lived species of rodents and birds showed rapid induction of ERK phosphorylation, with a decline to basal level within 60 min. In contrast, cells from longer-lived species showed slower and more prolonged activation of ERK phosphorylation. These results suggest that fibroblasts from long-lived species may be less susceptible to the early phases of damage from cadmium or peroxide and suggest that altered kinetics of ERK activity may contribute to their stress resistance properties. PMID- 24219323 TI - Impact of Diet Composition on Blood Glucose Regulation. AB - Nutritional management of blood glucose levels is a strategic target in the prevention and management of type 2 diabetes mellitus (T2DM). To implement such an approach, it is essential to understand the effect of food on glycemic regulation and on the underlying metabolic derangements. This comprehensive review summarizes the results from human dietary interventions exploring the impact of dietary components on blood glucose levels. Included are the major macronutrients; carbohydrate, protein and fat, micronutrient vitamins and minerals, nonnutrient phytochemicals and additional foods including low-calorie sweeteners, vinegar, and alcohol. Based on the evidence presented in this review, it is clear that dietary components have significant and clinically relevant effects on blood glucose modulation. An integrated approach that includes reducing excess body weight, increased physical activity along with a dietary regime to regulate blood glucose levels will not only be advantages in T2DM management, but will benefit the health of the population and limit the increasing worldwide incidence of T2DM. PMID- 24219325 TI - Combined analysis of gamma-H2AX/53BP1 foci and caspase activation in lymphocyte subsets detects recent and more remote radiation exposures. AB - Analysis of gamma-H2AX foci in blood lymphocytes is a promising approach for rapid dose estimation to support patient triage after a radiation accident but has one major drawback: the rapid decline of foci levels post-exposure cause major uncertainties in situations where the exact timing between exposure and blood sampling is unknown. To address this issue, radiation-induced apoptosis (RIA) in lymphocytes was investigated using fluorogenic inhibitors of caspases (FLICA) as an independent biomarker for radiation exposure, which may complement the gamma-H2AX assay. Ex vivo X-irradiated peripheral blood lymphocytes from 17 volunteers showed dose- and time-dependent increases in radiation-induced apoptosis over the first 3 days after exposure, albeit with considerable interindividual variation. Comparison with gamma-H2AX and 53BP1 foci counts suggested an inverse correlation between numbers of residual foci and radiation induced apoptosis in lymphocytes at 24 h postirradiation (P = 0.007). In T-helper (CD4), T-cytotoxic (CD8) and B-cells (CD19), some significant differences in radiation induced DSBs or apoptosis were observed, however no correlation between foci and apoptosis in lymphocyte subsets was observed at 24 h postirradiation. While gamma-H2AX and 53BP1 foci were rapidly induced and then repaired after exposure, radiation-induced apoptosis did not become apparent until 24 h after exposure. Data from six volunteers with different ex vivo doses and post-exposure times were used to test the capability of the combined assay. Results show that simultaneous analysis of gamma-H2AX and radiation-induced apoptosis may provide a rapid and more accurate triage tool in situations where the delay between exposure and blood sampling is unknown compared to gamma-H2AX alone. This combined approach may improve the accuracy of dose estimations in cases where blood sampling is performed days after the radiation exposure. PMID- 24219324 TI - Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model. AB - Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure. PMID- 24219326 TI - Chronic bronchitis in the cohort of Mayak workers first employed 1948-1958. AB - Incidence of chronic bronchitis has been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2005. Information on external gamma doses is available for virtually all of these workers; in contrast, plutonium body burden was measured only for 30% of workers. During the follow-up period in the study cohort 1,175 incident cases of chronic bronchitis were verified. The analyses of nonradiation factors revealed that the underlying risk of chronic bronchitis incidence increased with increasing attained age and was higher among smokers compared with never-smokers as would be expected. The most interesting finding in relationship to nonradiation factors was a sharp increase in the baseline chronic bronchitis risk before 1960. The cause of this is not clear but a number of factors may play a role. Based on the follow-up data after 1960, the analysis showed a statistically significant linear dose response relationship with cumulative external gamma-ray dose (ERR/Gy = 0.14, 95% CI 0.01, 0.32). Based on the same subset but with an additional restriction to members with cumulative internal lung dose below 1 Gy, a statistically significant linear dose response relationship with internal alpha-radiation lung dose from incorporated plutonium was found (ERR/Gy = 2.70, 95% CI 1.20, 4.87). In both cases, adjustment was made for nonradiation factors, including smoking and either internal or external dose as appropriate. At present there are no similar incidence studies with which to compare results. However, the most recent data from the atomic bomb survivor cohort (the Life Span Study) showed statistically significant excess mortality risk for respiratory diseases of 22% per Gy and this value is within the confidence bounds of the point estimate of the risk from this study in relation to external dose. PMID- 24219327 TI - Co-inoculating ruminal content neither provides active hydrolytic microbes nor improves methanization of 13C-cellulose in batch digesters. AB - Cellulose hydrolysis often limits the kinetics and efficiency of anaerobic degradation in industrial digesters. In animal digestive systems, specialized microorganisms enable cellulose biodegradation at significantly higher rates. This study aims to assess the potential of ruminal microbial communities to settle and to express their cellulolytic properties in anaerobic digesters. Cellulose-degrading batch incubations were co-inoculated with municipal solid waste digester sludge and ruminal content. 13C-labeled cellulose degradation was described over time with Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry. Results were linked to the identification of the microorganisms assimilating 13C and to the monitoring of their relative dynamics. Cellulose degradation in co-inoculated incubations was efficient but not significantly improved. Transient disturbances in degradation pathways occurred, as revealed by propionate accumulation. Automated Ribosomal Intergenic Spacer Analysis dynamics and pyrosequencing revealed that expected classes of Bacteria and Archaea were active and degraded cellulose. However, despite the favorable co-inoculation conditions, molecular tools also revealed that no ruminal species settled in the bioreactors. Other specific parameters were probably needed for this to happen. This study shows that exploiting the rumen's cellulolytic properties in anaerobic digesters is not straightforward. Co-inoculation can only be successful if ruminal microorganisms manage to thrive in the anaerobic digester and outcompete native microorganisms, which requires specific nutritional and environmental parameters, and a meticulous reproduction of the selection pressure encountered in the rumen. PMID- 24219328 TI - Sorghum seed maturity affects the weight and feeding duration of immature corn earworm, Helicoverpa zea, and fall armyworm, Spodoptera frugiperda, in the laboratory. AB - Corn earworm, Helicoverpa zea Boddie (Lepidoptera: Noctuidae), and fall armyworm, Spodoptera frugiperda J.E. Smith, are occasional pests in sorghum, Sorghum bicolor L. Moench (Poales: Poaceae), and can be economically damaging when conditions are favorable. Despite the frequent occurrence of mixed-species infestations, the quantitative data necessary for developing yield loss relationships for S. frugiperda are not available. Although these species share similar biological characteristics, it is unknown whether their damage potentials in developing grain sorghum panicles are the same. Using no-choice feeding assays in the laboratory, this study examined larval growth and feeding duration for H. zea and S. frugiperda in the absence of competition. Each species responded positively when exposed to sorghum seed in the soft-dough stage, supporting evidence for the interactions between host-quality and larval growth and development. The results of this study also confirmed the suitability of using laboratory-reared H. zea to develop sorghum yield loss estimates in the field, and provided insights into the biological responses of S. frugiperda feeding on developing sorghum seed. PMID- 24219329 TI - Sublethal exposure to crude oil enhances positive phototaxis in the calanoid copepod Calanus finmarchicus. AB - We investigated the effects of exposure to sublethal concentrations of the water accommodated fraction (WAF) of fresh crude oil on phototactic behavior of the calanoid copepod Calanus finmarchicus (Gunnerus) copepodite stage 5 (C5). Exposure was conducted in closed bottle systems, and behavior was tested in a tailored setup. Exposure times were 24, 48, 72, and 96 h, and the chosen exposure concentration was 25% of the recorded LC50 value for the WAF (309 +/- 32 MUg/L total hydrocarbon, including 20.37 +/- 0.51 MUg/L total PAH). The exposure significantly increased the positive phototactic behavior of the copepods after 24 h exposure and a similar significant effect was observed for all exposure durations. Additionally, experiments were conducted with nonexposed copepods with low lipid reserves. The main effect of the exposure was a shift in the response to light toward a more positive phototaxis, similar to that observed in nonexposed C. finmarchicus with low lipid reserves. The observed change in phototactic behavior observed in these studies suggests that the depth distribution of this species could be altered following an oil spill. Thus, further research is warranted to determine the possible interactive effects of light and oil spill exposures on Calanus population dynamics under field conditions. PMID- 24219330 TI - Guideline: the laboratory diagnosis of malaria. General Haematology Task Force of the British Committee for Standards in Haematology. AB - UK National External Quality Assessment Service surveys indicate continuing problems in malaria diagnosis: inaccurate calculation of parasitaemia or failure to estimate it altogether, difficulty distinguishing Plasmodium vivax from P. ovale, reporting malaria parasites when none were present and misidentification of P. falciparum as another species still occur. Therefore, the British Committee for Standards in Haematology Guidelines for the Laboratory Diagnosis of Malaria have been revised. They are intended for use in the UK but may also prove useful in other non-endemic areas. Routine use of thick and thin films is advised for malaria diagnosis. Thick films should be stained using Giemsa or Field stain. Thin films should be stained with Giemsa stain or Leishman stain. Thick films should be examined by two observers, each viewing a minimum of 200 high power fields. If thick films are positive, the species should be determined by examination of a thin film. In the case of P. falciparum or P. knowlesi infection, the percentage of parasitized cells or the number of parasites per microlitre (/MUl) should be estimated and reported. Rapid diagnostic tests (RDTs) for malarial antigen cannot replace microscopy but are indicated as a supplementary test when malaria diagnosis is performed by relatively inexperienced staff. Malaria RDTs are negative in babesiosis. PMID- 24219331 TI - Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-kappaB signalling. AB - Chronic lymphocytic leukaemia (CLL) is a disease with a highly variable prognosis. The clinical course can however be predicted thanks to prognostic markers. Poor prognosis is associated with expression of a B cell receptor (BCR) from unmutated immunoglobulin variable heavy-chain genes (IGHV) and expression of zeta-associated protein of 70 kDa (ZAP70). The reason why ZAP70 expression is associated with poor prognosis and whether the protein has a direct pathogenic function is at present unknown. By transfer of ZAP70 to CLL cells, we show here that expression of ZAP70 in CLL cells leads to increased expression of the nuclear factor (NF)-kappaB target genes interleukin-1beta (IL1B), IL6 and IL8 upon BCR triggering. This could be blocked by inhibition of NF-kappaB signalling through inhibition of IkappaB kinases (IKK). Transcriptome analysis identified a NF-kappaB RELA signature imposed by ZAP70 expression in BCR-stimulated CLL cells. We conclude that ZAP70 acts directly as an amplifier of NF-kappaB signalling in CLL cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target. PMID- 24219332 TI - Prevalence of thrombophilia according to age at the first manifestation of venous thromboembolism: results from the MAISTHRO registry. AB - Thrombophilia is a well-established risk factor for a venous thromboembolic event (VTE), and it has been proposed that hereditary thrombophilia may substantially contribute to the development of VTE in young patients. We aimed to analyse the prevalence of thrombophilia with special regard to the age of VTE manifestation. The study cohort consisted of 1490 patients (58% females) with a median age 43 years at the time of their first VTE. At least one thrombophilic disorder was identified in 50.1% of patients. The probability of detecting a hereditary thrombophilia declined significantly with advancing age (from 49.3% in patients aged 20 years and younger to 21.9% in patients over the age of 70 years; P < 0.001). This may be primarily attributed to the decreasing frequencies of the F5 R506Q (factor V Leiden) mutation and deficiencies of protein C or protein S with older age at the time of the initial VTE event. Moreover, thrombophilia was more prevalent in unprovoked compared with risk-associated VTE (57.7% vs. 47.7%; P = 0.001). The decline in the prevalence of hereditary thrombophilia with older ages supports the use of a selected thrombophilia screening strategy dependent on age and the presence or absence of additional VTE risk factors. PMID- 24219333 TI - Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis. AB - There is increasing recognition that thrombotic complications may occur in patients with cirrhosis, and literature on antithrombotic treatment in these patients is rapidly emerging. Due to extensive haemostatic changes in patients with cirrhosis, careful monitoring of anticoagulant therapy may be required. Recent data suggest that plasma levels of low molecular weight heparin (LMWH) are substantially underestimated by the anti-activated factor X (anti-Xa) assay in patients with cirrhosis. We studied the in vitro recovery of antithrombin (AT) dependent and -independent anticoagulant drugs in plasma from 26 patients with cirrhosis and 30 healthy controls and found substantially reduced anti-Xa levels when AT-dependent anticoagulant drugs were added to the plasma of patients with cirrhosis. LMWH (0.2 U/ml) had the poorest recovery in plasma from patients with cirrhosis (0.13 +/- 0.06 U/ml, compared to 0.23 +/- 0.03 U/ml in controls, P < 0.0001), followed by unfractionated heparin and fondaparinux. In contrast, the recovery of rivaroxaban and dabigatran was identical between patients and controls. These data suggest that the anti-Xa assay cannot be used to monitor AT dependent anticoagulant drugs in patients with cirrhosis, as it substantially underestimates drug levels. The direct factor Xa and IIa inhibitors, however, may be monitored through the respective anti-Xa and anti-IIa assays in patients with cirrhosis. PMID- 24219334 TI - Correlating prothrombin time with plasma rivaroxaban level. PMID- 24219335 TI - Community perceptions of health insurance and their preferred design features: implications for the design of universal health coverage reforms in Kenya. AB - BACKGROUND: Health insurance is currently being considered as a mechanism for promoting progress to universal health coverage (UHC) in many African countries. The concept of health insurance is relatively new in Africa, it is hardly well understood and remains unclear how it will function in countries where the majority of the population work outside the formal sector. Kenya has been considering introducing a national health insurance scheme (NHIS) since 2004. Progress has been slow, but commitment to achieve UHC through a NHIS remains. This study contributes to this process by exploring communities' understanding and perceptions of health insurance and their preferred designs features. Communities are the major beneficiaries of UHC reforms. Kenyans should understand the implications of health financing reforms and their preferred design features considered to ensure acceptability and sustainability. METHODS: Data presented in this paper are part of a study that explored feasibility of health insurance in Kenya. Data collection methods included a cross-sectional household survey (n = 594 households) and focus group discussions (n = 16). RESULTS: About half of the household survey respondents had at least one member in a health insurance scheme. There was high awareness of health insurance schemes but limited knowledge of how health insurance functions as well as understanding of key concepts related to income and risk cross-subsidization. Wide dissatisfaction with the public health system was reported. However, the government was the most preferred and trusted agency for collecting revenue as part of a NHIS. People preferred a comprehensive benefit package that included inpatient and outpatient care with no co-payments. Affordability of premiums, timing of contributions and the extent to which population needs would be met under a contributory scheme were major issues of concern for a NHIS design. Possibilities of funding health care through tax instead of NHIS were raised and preferred by the majority. CONCLUSION: This study provides important information on community understanding and perceptions of health insurance. As Kenya continues to prepare for UHC, it is important that communities are educated and engaged to ensure that the NHIS is acceptable to the population it serves. PMID- 24219336 TI - Experimental assessment of oral hygiene achieved by children wearing rapid palatal expanders, comparing manual and electric toothbrushes. AB - OBJECTIVES: The aim was to compare the efficacy of the electric versus the manual toothbrush in terms of the oral hygiene achieved by patients wearing rapid palatal expanders (RPEs). METHODS: Forty patients were randomly divided into two groups; one equipped with a manual toothbrush (Group A), the other with an electric toothbrush (Group B). Each child's plaque index (PI) and gingival index (GI) were calculated at banded molar level at times T0 (before banding), T1 (a month later), T2 (3 months later) and T3 (when the expander was removed). At each appointment, the PI and GI were recorded and the patient was remotivated. RESULTS: The level of oral hygiene achieved by the group using an electric toothbrush produced a greater improvement in the two indexes than in the group using the manual toothbrush that showed no statistically significant improvement (PI T0-T3: P = 0.309; GI T0-T3: P = 0.141). Both indexes dropped considerably in both groups from T0 to T2, but more so in the group B. From T2 to T3, although the electric toothbrush continued to be substantially more effective, Group B showed a statistically significant deterioration in the oral hygiene (PI +20%; GI +33%). Other assessments conducted on particular areas of the tooth showed improvements in the PI (-33%) for the vestibular region, and for the GI (-57%) in the palatal region among the patients in Group B, while there were no significant changes in these indexes in Group A. CONCLUSIONS: Our findings show that the electric toothbrush is statistically more efficient in performing an adequate level of oral hygiene in children wearing RPE. PMID- 24219337 TI - Supramolecular assistance for the selective monofunctionalization of a calix[6]arene tris-carboxylic acid-based receptor. AB - The selective functionalization of macrocyclic receptors remains extremely challenging because it generally requires the transformation of one and only one functional group among several identical groups. Recently, some of us described that the host-guest properties of a calix[6]arene-based Zn complex could be exploited for its selective monofunctionalization. Herein, we report on the extension of this synthetic strategy to a calix[6]arene-based receptor displaying a different recognition pattern with its guest. More precisely, a calix[6]arene tris-carboxylic acid-based receptor bearing three azido groups at the large rim was selectively monofunctionalized through an intramolecular thermal Huisgen reaction with a hexynNH3(+) ion accommodated into the cavity. This work shows that the monofunctionalization methodology can also be performed efficiently with host-guest systems involving ionic/H-bonding interactions, and it is thus not limited only to the use of metal-ligand interactions. In other words, this supramolecular methodology can be used as a general tool for the selective functionalization of molecular receptors. PMID- 24219338 TI - Role of endoscopic ultrasonography in pancreatic cystic neoplasms: where do we stand and where will we go? AB - We increasingly encounter pancreatic cystic neoplasms (PCN) in clinical practice and the differential diagnoses vary widely from benign to malignant. There is no 'one and only' diagnostic procedure for PCN. Multiple modalities including computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS) are widely used, but EUS has the advantage of anatomical proximity to the pancreas and upper gastrointestinal tract. In addition, EUS-guided fine-needle aspiration (EUS-FNA) provides both cytological evaluation and cyst fluid analysis. Although the role of EUS-FNA for PCN is established, the sensitivity of cytology is low and cyst fluid analysis is only useful for differentiation between mucinous and non mucinous cysts. Recently, novel through-the-needle imaging under EUS-FNA, such as confocal laserendomicroscopy, is expected to attribute to a better diagnostic yield. Moreover, feasibility of cyst ablation has been reported and the role of EUS has expanded from diagnosis to treatment. However, clinical impact of cyst ablation in terms of safety, efficacy and cost-effectiveness should be validated further. In summary, EUS and EUS-guided intervention does and will play a central role in the management of PCN from surveillance to treatment, but many clinical questions remain unanswered, which warrants well-designed prospective clinical trials. PMID- 24219339 TI - The impact of the width of the tracking area on speckle tracking parameters methodological aspects of deformation imaging. AB - AIMS: The aim of this study was to analyze the impact of the tracking area width on myocardial wall motion and deformation parameters in 2D speckle tracking. METHODS AND RESULTS: Standardized apical views were acquired in 30 healthy subjects and 15 patients with left ventricular systolic dysfunction using 2D echocardiography. Longitudinal peak systolic strain (PSS), longitudinal peak systolic strain rate (PSSR), postsystolic index (PSI), peak longitudinal (PLD), and peak transverse displacement (PTD) were determined by 2D speckle tracking to analyze the impact of the tracking area width on global and regional myocardial wall motion and deformation parameters. The dimension of the tracking area has a significant impact on all parameters. With increasing width of the tracking area higher values of PSS, PSSR, PSI, and lower values of PLD and PTD were determined. With increasing width of the tracking area a significant number of segments were not tracked. In summary, especially global PSS is significantly influenced by the width of the tracking area. CONCLUSIONS: The strain values determined by 2D speckle tracking are significantly influenced by the tracking area width. The tracking of the subendocardial layers only results in lower global strain values than tracking the complete ventricular wall using the medium or wide tracking area widths. The tracking quality in the far field is worse if the tracking area is too wide. The present data show that standard and reference values of deformation imaging should include detailed information about the position and the width of the tracking area. PMID- 24219340 TI - Characterization of oleanolic acid derivative for colon cancer targeting with positron emission tomography. AB - Abstract Oleanolic acid (OA) is a pentacyclic triterpenoid found in various plant species. Triterpenoid compounds have been shown to inhibit tumor proliferation and to induce apoptosis in cancer cells. We synthesized an OA derivative and evaluated its inhibitory effects on cell proliferation in human colon cancer. Radioisotope-labeled OA was prepared for noninvasive monitoring of tumor progression in vitro and in vivo. The OA derivative decreased cell survival in a concentration-dependent manner and increased apoptosis in HT-29 cells. Furthermore, it induced downregulation of cyclin D1, Cox-2, Bcl-2 and Bcl-xL mRNA expression and upregulation of the mRNA expression of the anti-apoptotic Bax protein in HT29 cells. NF-kappaB p65 and IkappaB expression also decreased, whereas expression of the apoptosis marker, the cleaved form of PARP-1, significantly increased in OA derivative-treated HT-29 cells. Radioisotope labeled OA (68Ga-NOTA-OA) showed significantly high tumor uptake, as assessed by biodistribution and positron emission tomography imaging analyses, at 1 h post injection in the human colon cancer xenograft model. Our results demonstrate that the OA derivative has promising properties as an anticancer drug and as an imaging tool for tumor targeting. PMID- 24219341 TI - EurOOHnet-the European research network for out-of-hours primary health care. AB - BACKGROUND AND RATIONALE: European countries face similar challenges in the provision of health care. Demographic factors like ageing, population growth, changing patient behaviour, and lack of work force lead to increasing demands, costs, and overcrowding of out-of-hours (OOH) care (i.e. primary care services, emergency departments (EDs), and ambulance services). These developments strain services and imply safety risks. In the last few decades, countries have been re organizing their OOH primary health care services. AIM AND SCOPE OF THE NETWORK: We established a European research network for out-of-hours primary health care (EurOOHnet), which aims to transfer knowledge, share experiences, and conduct research. Combining research competencies and integrating results can generate a profound information flow to European researchers and decision makers in health policy, contributing towards feasible and high-quality OOH care. It also contributes to a more comparable performance level within European regions. CONDUCTED RESEARCH PROJECTS: The European research network aims to conduct mutual research projects. At present, three projects have been accomplished, among others concerning the diagnostic scope in OOH primary care services and guideline adherence for diagnosis and treatment of cystitis in OOH primary care. THE FUTURE: Future areas of research will be organizational models for OOH care; appropriate use of the OOH services; quality of telephone triage; quality of medical care; patient safety issues; use of auxiliary personnel; collaboration with EDs and ambulance care; and the role of GPs in OOH care. PMID- 24219342 TI - EFPC: European Forum for Primary Care. EC Integrated Care Collaborative needs good practices to extend healthy life years of EU citizens. PMID- 24219343 TI - Effects of writing down the request for help: a randomized controlled trial. AB - BACKGROUND: Studies investigating interventions, aimed at improving patient satisfaction by exploring the patient's request for help, show conflicting results. OBJECTIVES: To investigate whether writing down the request for help on a request card, prior to the consultation improves patient satisfaction. METHODS: This study was a single-blind randomized controlled trial, in which the patients were blinded to the intervention. Patients were recruited in two rural practices (five GPs) and one urban practice (four GPs) in The Netherlands. Consecutive patients with a new request for help were asked to participate. All patients received general information about patient satisfaction. After randomization, patients in the intervention group were asked to fill in a card with their request(s) for help; the general practitioners started the consultations with these questions. We used the 'Professional Care' subscale of the Consultation Satisfaction Questionnaire (CSQ) to examine the effect of the intervention on patient satisfaction. Secondary outcomes were patient satisfaction measured with the patient's VAS score, the GP's VAS score on satisfaction, consultation time, the other subscales of the CSQ, and the number of consultations during follow-up. RESULTS: There was no difference in patient satisfaction (CSQ, VAS) between both groups. We also did not find any differences between the other subscales of the CSQ. CONCLUSION: A beneficial effect of the use of a 'request card' by the patient on patient satisfaction of the consultation could not be demonstrated. PMID- 24219344 TI - Would GPs advise patients with respiratory tract infections to refrain from exercise, stay indoors or stay in bed? Survey of GPs in Poland and Norway. AB - BACKGROUND: For patients with respiratory tract infections evidence regarding bed rest, staying indoors and refraining from exercise is sparse. OBJECTIVES: To explore how general practitioners (GPs) in Poland and Norway would advise such patients. METHODS: Convenience samples of GPs in Poland (n = 216) and Norway (n = 171) read four vignettes in which patients presented symptoms consistent with pneumonia, sinusitis, common cold and exacerbation of chronic obstructive pulmonary disease (COPD), respectively. For each vignette, GPs were asked whether they would recommend staying indoors, staying in bed and refraining from exercise, and if so, for how many days. RESULTS: For each vignette, the proportions of GPs recommending the patient to stay indoors in Poland versus Norway were 98% versus 72% (pneumonia), 92% versus 26% (sinusitis), 87% versus 9% (common cold) and 92% versus 39% (exacerbation of COPD). In regression analysis adjusted relative risks (95% CI) for recommending the patient to stay indoors in Poland versus Norway was 1.4 (1.2-1.5), 3.7 (2.8-4.8), 10.6 (6.3-17.7) and 2.5 (2.0-3.1), respectively. Among those who would recommend the patient to stay indoors, mean durations were 8.1, 6.6, 5.1 and 6.7 days in Poland versus 3.2, 2.8, 2.6 and 4.1 days in Norway, respectively. Polish GPs were also more likely to recommend staying in bed and refraining from exercise, and for a longer time, than their Norwegian colleagues. CONCLUSION: GPs in Poland were more likely to recommend bed rest, staying indoors and refraining from exercise. This suggests that they perceived the cases as more serious than their Norwegian colleagues. PMID- 24219345 TI - Why do GPs continue inappropriate hospital prescriptions of proton pump inhibitors? A qualitative study. AB - BACKGROUND: Inappropriate prescriptions of Proton pump inhibitors (PPIs) initiated in hospitals are frequently continued in primary care. No research has explored why general practitioners (GPs) continue or discontinue inappropriate drug therapy. OBJECTIVES: This study aims to describe factors and motives associated with the continuation of inappropriate prescriptions of PPIs in primary care. METHODS: Semi-structured qualitative interviews on basis of a purposive sampling of five GPs who often continued inappropriate prescriptions and five GPs who frequently discontinued inappropriate drug therapy with PPIs (10 GPs total, of which four were female and six male). RESULTS: Although all GPs enrolled in the study were enthusiastic about the effectiveness of PPIs, differences between the continuing and discontinuing GPs exists in three areas: The two groups varied ( 1 ) in awareness of indications and general attitudes towards prescribing ( 2 ) in perception of the hospital physicians' competence in prescribing and ( 3 ) appreciation of general prescribing conditions in hospitals. CONCLUSION: Differences between the continuing and discontinuing GPs were found in their level of knowledge and their perceptions of the hospital physicians' competence and the threshold to prescribing in hospitals. Financial pressure and possible adverse effects demand a more balanced and evidence-based prescribing of PPIs. Attempts to change behaviour should focus on the GPs' awareness of indications for PPIs, NSAID risks, and prescribing approaches in hospitals. Default prescribing in hospital demands critical examination. PMID- 24219346 TI - Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries. AB - A family of self-replicating macrocycles was developed using dynamic combinatorial chemistry. Replication is driven by self-assembly of the replicators into fibrils and relies critically on mechanically induced fibril fragmentation. Analysis of separate dynamic combinatorial libraries made from one of six peptide-functionalized building blocks of different hydrophobicity revealed two selection criteria that govern the emergence of replicators from these systems. First, the replicators need to have a critical macrocycle size that endows them with sufficient multivalency to enable their self-assembly into fibrils. Second, efficient replication occurs only for library members that are of low abundance in the absence of a replication pathway. This work has led to spontaneous emergence of replicators with unrivalled structural complexity, being built from up to eight identical subunits and reaching a MW of up to 5.6 kDa. The insights obtained in this work provide valuable guidance that should facilitate future discovery of new complex self-replicating molecules. They may also assist in the development of new self-synthesizing materials, where self-assembly drives the synthesis of the very molecules that self-assemble. To illustrate the potential of this concept, the present system enables access to self-assembling materials made from self-synthesizing macrocycles with tunable ring size ranging from trimers to octamers. PMID- 24219347 TI - Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis. AB - Our objective was to investigate spinal cord (SC) atrophy in amyotrophic lateral sclerosis (ALS) patients, and to determine whether it correlates with clinical parameters. Forty-three patients with ALS (25 males) and 43 age- and gender matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images covering the whole brain and the cervical SC to estimate cervical SC area and eccentricity at C2/C3 level using validated software (SpineSeg). Disease severity was quantified with the ALSFRS-R and ALS Severity scores. SC areas of patients and controls were compared with a Mann-Whitney test. We used linear regression to investigate association between SC area and clinical parameters. Results showed that mean age of patients and disease duration were 53.1 +/- 12.2 years and 34.0 +/- 29.8 months, respectively. The two groups were significantly different regarding SC areas (67.8 +/- 6.8 mm2 vs. 59.5 +/- 8.4 mm2, p < 0.001). Eccentricity values were similar in both groups (p = 0.394). SC areas correlated with disease duration (r = - 0.585, p < 0.001), ALSFRS-R score (r = 0.309, p = 0.044) and ALS Severity scale (r = 0.347, p = 0.022). In conclusion, patients with ALS have SC atrophy, but no flattening. In addition, SC areas correlated with disease duration and functional status. These data suggest that quantitative MRI of the SC may be a useful biomarker in the disease. PMID- 24219349 TI - miR-203 inhibits the proliferation and self-renewal of esophageal cancer stem like cells by suppressing stem renewal factor Bmi-1. AB - Cancer stem-like cells exist in many malignancies and several stem cell-related genes and microRNAs, such as Bmi-1 and miR-203, have been identified as cancer stem-like cell regulators using gene microarray or sequencing analysis. Previously, we used side population (SP) sorting to enrich cancer stem-like cells from esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results demonstrated that EC9706 SP cells shared common features of cancer stem-like cells. In this study, we examined the expression of Bmi-1 and miR-203 in ESCC SP and non-SP (NSP) cells. Our results showed that, when compared with NSP cells, Bmi-1 was up-regulated and miR-203 was down-regulated in SP cells. During the differentiation from SP to NSP cells, the expression levels of Bmi-1 were gradually decreased. Overexpression of miR-203 resulted in a significant reduction of endogenous Bmi-1 protein level in EC9706 cells. SP and NSP analyses revealed that the SP cell fraction was markedly decreased in miR-203 overexpressed cells. miR-203 overexpressed cells also showed a significant reduction in colony formation, which was resistant to chemotherapeutic drug treatment and tumorigenicity in nude mice. Rescue experiments demonstrated that ectopic expression of Bmi-1 in miR-203 overexpressed cells increased the SP fraction and restored cell proliferation. Taken together, these results indicated that stem renewal factor Bmi-1 was a direct target of miR-203. The regulation of Bmi-1 by miR-203 may play an important role in controlling cell proliferation and self-renewal of esophageal cancer stem-like cells. It may also promote the development of new therapeutic strategies and efficient drugs that target ESCC stem-like cells. PMID- 24219348 TI - Patterns in blood pressure medication use in US incident dialysis patients over the first 6 months. AB - BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered. PMID- 24219351 TI - Negative, not positive symptoms predict the early therapeutic alliance in cognitive behavioral therapy for psychosis. AB - OBJECTIVE: The strength of therapeutic alliance is consistently associated with therapy outcome. The aim of this study was to identify relevant predictors for early therapeutic alliance in cognitive behavioral therapy for psychosis. METHOD: Fifty-six patients with schizophrenia spectrum disorders were included in the analysis. Possible predictors (positive and negative symptoms, depression, insight, social functioning, theory of mind, and medication adherence) were assessed at baseline. Alliance was assessed after each therapy session. RESULTS: Lower negative symptoms significantly predicted higher patient and therapist rated alliance. CONCLUSIONS: The findings indicate that negative symptoms might be a barrier to the development of therapeutic alliance. Assumed underlying processes and practical implications are discussed. PMID- 24219350 TI - Characterization of NCR1+ cells residing in lymphoid tissues in the gut of lambs indicates that the majority are NK cells. AB - Natural killer (NK) cells are important for immune protection of the gut mucosa. Previous studies have shown that under pathologic conditions NK cells, T cells and dendritic cells are found co-localised in secondary lymphoid organs where their interaction coordinates immune responses. However, in the gut-associated lymphoid tissues (GALTs), there are few detailed reports on the distribution of NK cells. Sheep harbour several types of organised lymphoid tissues in the gut that have different functions. The ileal Peyer's patch (IPP) functions as a primary lymphoid tissue for B cell generation, while the jejunal Peyer's patches (JPPs) and colon patches (CPs) are considered secondary lymphoid tissues. In the present study, we analysed tissues from healthy lambs by flow cytometry and in situ multicolour immunofluorescence, using recently described NCR1 antibodies to identify ovine NK cells. Most NCR1+ cells isolated from all tissues were negative for the pan T cell marker CD3, and thus comply with the general definition of NK cells. The majority of NCR1+ cells in blood as well as secondary lymphoid organs expressed CD16, but in the GALT around half of the NCR1+ cells were negative for CD16. A semi-quantitative morphometric study on tissue sections was used to compare the density of NK cells in four compartments of the IPPs, JPP and CPs. NCR1+ cells were found in all gut segments. Statistical analysis revealed significant differences between compartments of the primary lymphoid organ IPP and the secondary lymphoid organs of the JPPs and CP. NK cells co-localised and made close contact with T cells, dendritic cells and other NK cells, but did not show signs of proliferation. We conclude that NK cells are present in all investigated segments of the sheep gut, but that presence of other innate lymphoid cells expressing NCR1 cannot be excluded. PMID- 24219352 TI - 3 tesla magnetic resonance imaging of the occipitoatlantoaxial region in the normal horse. AB - The aim of this study was to describe the appearance of the ligamentous structures of the occipitoatlantoaxial (OAA) region in the normal horse by 3 tesla (3T) magnetic resonance imaging (MRI). The MRI images of the longitudinal odontoid ligament, tectorial membrane, dorsal and ventral atlantoaxial ligaments, dorsal atlantooccipital membrane with its reinforcing ligaments, and the lateral atlantooccipital ligaments of 10 horse cadavers were evaluated. All ligaments and membranes were identified in all planes, except for the lateral atlantooccipital ligament in the sagittal plane due to its cranioventrolateral course. All were iso to mildly hypointense to musculature of the neck in T1W with the exception of the tectorial membrane that was moderately hypointense; moderately hypointense in PD-SPIR, and markedly hypointense (isointense to cortical bone) in T2W. The PD SPIR was the best sequence to identify all ligaments and membranes from their cranial and caudal attachments. The longitudinal odontoid ligament, ventral atlantoaxial ligament, and reinforcing bands of the dorsal atlantooccipital membrane presented a characteristic striped heterogeneous signal behavior thought to be due to fibrocartilaginous content. The remaining ligaments and membranes showed homogeneous signal intensity. Special anatomical features in this species such as the fan-shaped longitudinal odontoid ligament, absence of the transverse ligament and presence of the ventral atlantoaxial ligament were documented. Ligamentous structures that stabilize the equine OAA region were described with MRI in this study and these findings could serve as an anatomic reference for those cases where instability of this region is suspected. PMID- 24219353 TI - Simultaneous quantification of nucleoproteins and comparison of methyl green pyronin Y and Feulgen staining in sections of oral squamous cell carcinoma, dysplastic lesions and normal mucosa. AB - A fundamental difference between normal cells and tumor cells is the proliferative activity of the nucleus and nucleolus, which increases progressively from normal to oral dysplastic mucosa to oral squamous cell carcinoma (OSCC). This activity is evaluated routinely using hematoxylin and eosin (H & E) staining, but in some cases, inter-observer variability occurs among pathologists. We evaluated cellular proliferation by staining sections with the methyl green-pyronin Y procedure and the Feulgen reaction. We also compared the efficacy of methyl green-pyronin Y and Feulgen staining for studying nuclear and nucleolar features in oral dysplastic mucosa and in different grades of OSCC. Sections cut from formalin fixed, paraffin embedded blocks of five normal mucosa, 15 dysplastic mucosa, 10 well-differentiated OSCC, 10 moderately differentiated OSCC and five poorly differentiated OSCC cases were stained with Hematoxylin and Eosin, methyl green-pyronin Y and the Feulgen reaction. The mean diameters of the nuclei and number of nucleoli showed significant differences. A progressive increase in diameter of the nucleus and number of nucleoli was observed from normal mucosa through poorly differentiated OSCC. We observed that methyl green pyronin Y stain is more useful than Feulgen and hematoxylin and eosin for simultaneous quantitative assessment of both RNA and DNA. The simplicity of this technique makes it a valuable tool even for daily routine examination. PMID- 24219354 TI - Effect of antimicrobial agents incorporated into resilient denture relines on the Candida albicans biofilm. AB - OBJECTIVE: The antimicrobial action of five drugs incorporated in temporary denture relines on the fungal biofilm was evaluated. MATERIALS AND METHODS: A Candida albicans biofilm (SC5314) was formed on specimens (10 * 1 mm) of materials (Trusoft and Softone) modified or not (control) by the drugs (nystatin, miconazole, ketoconazole, itraconazole, and chlorhexidine diacetate). Cell viability was determined spectrophotometrically by the tetrazolium salt reduction assay (XTT) after 24 h, 48 h, and 7 and 14 days of incubation. The minimum inhibitory concentrations (MICs) were those which inhibited 90% or more of fungal growth. Fungal susceptibility was confirmed by confocal laser scanning microscopy analysis. RESULTS: The MICs of drugs incorporated in the materials were 0.032, 0.256, 0.128, 0.256, and 0.064 g ml(-1) for nystatin, miconazole, ketoconazole, itraconazole, and chlorhexidine, respectively. Images from nystatin, chlorhexidine, and ketoconazole demonstrated no viable cells. CONCLUSIONS: The antimicrobials incorporated in the resilient materials inhibited fungal growth during 14 days, with lower MICs for nystatin and chlorhexidine. PMID- 24219355 TI - Synthesis and pH-responsive "schizophrenic" aggregation of a linear-dendron-like polyampholyte based on oppositely charged polypeptides. AB - A novel linear-dendron-like polyampholyte, poly(L-lysine)-b-D2-poly(L-glutamic acid) [PLL-b-D2-(PLGA)4], where D2 is the second generation of poly(amido amine), was prepared by hydrolyzing poly(epsilon-benzyloxycarbonyl-L-lysine)-b-D2 poly(gamma-benzyl-L-glutamate) copolymer which was synthesized via a combination of ring-opening polymerization and click chemistry. The pH-responsive self assembly behaviors of PLL-b-D2-(PLGA)4 were investigated in detail. It is found that PLL-b-D2-(PLGA)4 can self-assemble into PLGA-core aggregates at acidic pH and PLL-core aggregates at alkaline pH, which was accompanied with the coil-to helix conformational transition of PLGA and PLL segments, respectively. The self assembled aggregates with various morphologies, such as large compound micelles, worm-like micelles, large compound vesicles, simple vesicles, and rigid tubular structures have been obtained in "schizophrenic" aggregation process with simply increasing the solution pH. The hierarchical assembled fractal structures of PLL b-D2-(PLGA)4 were observed during the solvent evaporation at high pH value. PMID- 24219356 TI - Nutraceutical properties of extra-virgin olive oil: a natural remedy for age related disease? AB - The health benefits of the Mediterranean diet can be largely ascribed to the nutraceutical properties of extra-virgin olive oil (EVOO). Mono-unsaturated fatty acids and various phenolic compounds, such as oleocanthal, oleuropein, hydroxytyrosol, and tyrosol, are the main nutraceutical substances of EVOO. These substances have been suggested to have the ability to modulate aging-associated processes. In experimental models, it has been shown that EVOO with high concentrations of polyphenols has anti-inflammatory and anti-oxidant properties. Indeed, it was observed that hydroxytyrosol and oleocanthal inhibit the cyclooxygenases (COX-1 and -2) responsible for prostaglandin production; oleuropein is a radical scavenger that blocks the oxidation of low-density lipoproteins. Due to the relevance of olive oil in the economy of Sicily, our group has been funded to assess the nutraceutical properties of different kinds of olive oil. Indeed, the aim of the study is to evaluate effects of EVOOs, with low and high polyphenols content, on immuno-inflammatory and oxidative stress responses in young and old people. A further objective of our group is to evaluate effects of EVOO, with low and high polyphenol content, on the expression of genes encoding proteins that take part in the insulin/insulin-like growth factor-1 signaling pathway involved in longevity. The results of the study will be useful for producing olive oil enriched in nutraceutical properties that may be likely helpful in the prevention of age-related diseases. PMID- 24219357 TI - Niche partitioning in three sympatric congeneric species of dragonfly, Orthetrum chrysostigma, O. coerulescens anceps, and O. nitidinerve: the importance of microhabitat. AB - Habitat heterogeneity has been shown to promote co-existence of closely related species. Based on this concept, a field study was conducted on the niche partitioning of three territorial congeneric species of skimmers (Anisoptera: Libellulidae) in Northeast Algeria during the breeding season of 2011. According to their size, there is a descending hierarchy between Orthetrum nitidinerve Selys, O. chrysostigma (Burmeister), and O. coerulescens anceps (Schneider). After being marked and surveyed, the two latter species had the same breeding behavior sequence. Knowing that they had almost the same size, such species could not co-occur in the same habitat according to the competitive exclusion principle. The spatial distribution of the three species was investigated at two different microhabitats, and it was found that these two species were actually isolated at this scale. O. chrysostigma and O. nitidinerve preferred open areas, while O. c. anceps occurred in highly vegetated waters. This study highlights the role of microhabitat in community structure as an important niche axis that maintains closely related species in the same habitat. PMID- 24219361 TI - Sequestration of selenium on calcite surfaces revealed by nanoscale imaging. AB - Calcite, a widespread natural mineral at the Earth's surface, is well-known for its capacity to sequester various elements within its structure. Among these elements, selenium is important because of its high toxicity in natural systems and for human health. In the form of selenite (Se((IV))), selenium can be incorporated into calcite during growth. Our in situ atomic force microscopy observations of calcite surfaces during contact with selenium-bearing solutions demonstrate that another process of selenium trapping can occur under conditions in which calcite dissolves. Upon the injection of solutions containing selenium in two states of oxidation (either Se((IV)) or Se((VI))), precipitates were observed forming while calcite was still dissolving. In the presence of selenate (Se((VI))), the precipitates formed remained small during the observation period. When injecting selenite (Se((IV))), the precipitates grew significantly and were identified as CaSeO3.H2O, based on SEM observations, Raman spectroscopy, and thermodynamic calculations. An interpretation is proposed where the dissolution of calcite increases the calcium concentration in a thin boundary layer in contact with the surface, allowing the precipitation of a selenium phase. This process of dissolution-precipitation provides a new mechanism for selenium sequestration and extends the range of thermodynamic conditions under which such a process is efficient. PMID- 24219359 TI - Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma. AB - Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33.3% and 42.9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation. PMID- 24219360 TI - Serum liver enzymes are associated with all-cause mortality in an elderly population. AB - BACKGROUND & AIMS: Little is known about the association of serum liver enzymes with long-term outcome in the elderly. We sought to clarify the association of serum gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause and cause-specific mortality in an elderly population. METHODS: This study was embedded in the Rotterdam Study, a large population-based cohort of persons aged 55 years or older. Cox-regression analyses were performed to examine the association of baseline serum GGT, ALP, and aminotransferase levels with mortality, adjusted for age, sex, education, smoking status, alcohol intake, hypertension, diabetes mellitus, body mass index and total cholesterol levels. Liver enzyme levels were categorized according to sample percentiles; levels <25th percentile were taken as a reference. RESULTS: During a follow-up of up to 19.5 years, 2997 of 5186(57.8%) participants died: 672 participants died of causes related to cardiovascular diseases (CVD) and 703 participants died of cancer. All serum liver enzymes were associated with all-cause mortality (all P < 0.001). Moreover, GGT was associated with increased CVD mortality (P < 0.001), and ALP and AST with increased cancer-related mortality (P = 0.03 and P = 0.005 respectively). Participants with GGT and ALP in the top 5% had the highest risk for all-cause mortality (HR1.55; 95%CI 1.30-1.85 and HR1.49; 95%CI 1.25-1.78 respectively). AST and ALT <25th percentile were also associated with a higher risk of all-cause mortality. CONCLUSIONS: All serum liver enzymes were positively associated with long-term mortality in this elderly population. Why participants with low ALT and AST levels have higher risk of mortality remains to be elucidated. PMID- 24219358 TI - Gut microbiota-based translational biomarkers to prevent metabolic syndrome via nutritional modulation. AB - In the face of the global epidemic of metabolic syndrome (MetS) and its strong association with the increasing rate of cardiovascular morbidity and mortality, it is critical to detect MetS at an early stage in the clinical setting to implement preventive intervention long before the complications arise. Lipopolysaccharide, the cell wall component of Gram-negative bacteria produced from diet-disrupted gut microbiota, has been shown to induce metabolic endotoxemia, chronic low-grade inflammation, and ultimately insulin resistance. Therefore, ameliorating the inflammation and insulin resistance underlying MetS by gut microbiota-targeted, dietary intervention has gained increasing attention. In this review, we propose using dynamic monitoring of a set of translational biomarkers related with the etiological role of gut microbiota, including lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR), for early detection and prevention of MetS via nutritional modulation. LBP initiates the recognition and monomerization of lipopolysaccharide and amplifies host immune responses, linking the gut-derived antigen load and inflammation indicated by the plasma levels of CRP. Fasting plasma insulin and HOMA-IR are measured to evaluate insulin sensitivity that is damaged by pro-inflammatory cytokines. The dynamic monitoring of these biomarkers in high-risk populations may provide translational methods for the quantitative and dynamic evaluation of dysbiosis induced insulin resistance and the effectiveness of dietary treatment for MetS. PMID- 24219362 TI - Hospital process orientation from an operations management perspective: development of a measurement tool and practical testing in three ophthalmic practices. AB - BACKGROUND: Although research interest in hospital process orientation (HPO) is growing, the development of a measurement tool to assess process orientation (PO) has not been very successful yet. To view a hospital as a series of processes organized around patients with a similar demand seems to be an attractive proposition, but it is hard to operationalize this idea in a measurement tool that can actually measure the level of PO. This research contributes to HPO from an operations management (OM) perspective by addressing the alignment, integration and coordination of activities within patient care processes. The objective of this study was to develop and practically test a new measurement tool for assessing the degree of PO within hospitals using existing tools. METHODS: Through a literature search we identified a number of constructs to measure PO in hospital settings. These constructs were further operationalized, using an OM perspective. Based on five dimensions of an existing questionnaire a new HPO-measurement tool was developed to measure the degree of PO within hospitals on the basis of respondents' perception. The HPO-measurement tool was pre-tested in a non-participating hospital and discussed with experts in a focus group. The multicentre exploratory case study was conducted in the ophthalmic practices of three different types of Dutch hospitals. In total 26 employees from three disciplines participated. After filling in the questionnaire an interview was held with each participant to check the validity and the reliability of the measurement tool. RESULTS: The application of the HPO-measurement tool, analysis of the scores and interviews with the participants resulted in the possibility to identify differences of PO performance and the areas of improvement--from a PO point of view--within each hospital. The result of refinement of the items of the measurement tool after practical testing is a set of 41 items to assess the degree of PO from an OM perspective within hospitals. CONCLUSIONS: The development and practically testing of a new HPO-measurement tool improves the understanding and application of PO in hospitals and the reliability of the measurement tool. The study shows that PO is a complex concept and appears still hard to objectify. PMID- 24219363 TI - Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. AB - Natural antimicrobial peptides represent a primordial mechanism of immunity in both vertebrate and nonvertebrate organisms. Among them, histatins belong to a family of human salivary metal-binding peptides displaying potent antibacterial, antifungal and wound-healing activities. These properties, along with the ability of histatins to inhibit collagenases and cysteine proteases, have attracted much attention for their potential use in the treatment of several oral diseases. This review critically assesses the studies carried out to date in order to provide a comprehensive and systematic vision of the information accumulated so far. In particular, the relationship between metal-binding and peptide activity is extensively analysed. The review provides important clues for developing possible therapeutic applications of histatins and their synthetic peptide analogues by creating a set of necessary resource materials to support investigators and industries interested in exploiting their unique properties. PMID- 24219364 TI - FAst MEtabolizer (FAME): A rapid and accurate predictor of sites of metabolism in multiple species by endogenous enzymes. AB - FAst MEtabolizer (FAME) is a fast and accurate predictor of sites of metabolism (SoMs). It is based on a collection of random forest models trained on diverse chemical data sets of more than 20 000 molecules annotated with their experimentally determined SoMs. Using a comprehensive set of available data, FAME aims to assess metabolic processes from a holistic point of view. It is not limited to a specific enzyme family or species. Besides a global model, dedicated models are available for human, rat, and dog metabolism; specific prediction of phase I and II metabolism is also supported. FAME is able to identify at least one known SoM among the top-1, top-2, and top-3 highest ranked atom positions in up to 71%, 81%, and 87% of all cases tested, respectively. These prediction rates are comparable to or better than SoM predictors focused on specific enzyme families (such as cytochrome P450s), despite the fact that FAME uses only seven chemical descriptors. FAME covers a very broad chemical space, which together with its inter- and extrapolation power makes it applicable to a wide range of chemicals. Predictions take less than 2.5 s per molecule in batch mode on an Ultrabook. Results are visualized using Jmol, with the most likely SoMs highlighted. PMID- 24219365 TI - Estimate of production of gaseous nitrogen in the human body based on (15)N analysis of breath N2 after administration of [(15)N2]urea. AB - After oral administration of [(15)N2]urea (1.5 mmol, 95 atom% (15)N), we found that breath N2 was significantly (15)N-labelled. The result suggests that molecular nitrogen in breath must be partly produced endogenously. Based on a metabolic model, the endogenous N2 production was estimated to be 0.40+/-0.25 mmol kg(-1) d(-1) or 2.9+/-1.8 % of the total (urinary and faecal) N excretion in fasted healthy subjects (n=4). In patients infected with Helicobacter pylori (n=5), the endogenous N2 production was increased to 1.24+/-0.59 mmol kg(-1) d( 1) or 9.0+/-4.3 % of the total N excretion compared to the healthy controls (p<0.05). We conclude that N balance and gas exchange measurements may be affected by endogenously produced nitrogen, especially in metabolic situations with elevated nitrosation, for instance in oxidative and nitrosative stress related diseases such as H. pylori infections. PMID- 24219366 TI - Side chain dynamics of carboxyl and carbonyl groups in the catalytic function of Escherichia coli ribonuclease H. AB - Many proteins use Asx and Glx (x = n, p, or u) side chains as key functional groups in enzymatic catalysis and molecular recognition. In this study, NMR spin relaxation experiments and molecular dynamics simulations are used to measure the dynamics of the side chain amide and carboxyl groups, (13)C(gamma/delta), in Escherichia coli ribonuclease HI (RNase H). Model-free analysis shows that the catalytic residues in RNase H are preorganized on ps-ns time scales via a network of electrostatic interactions. However, chemical exchange line broadening shows that these residues display significant conformational dynamics on MUs-ms time scales upon binding of Mg(2+) ions. Two groups of catalytic residues exhibit differential line broadening, implicating distinct reorganizational processes upon binding of metal ions. These results support the "mobile metal ion" hypothesis, which was inferred from structural studies of RNase H. PMID- 24219367 TI - Effectiveness and safety of erythropoiesis-stimulating agent use in the perioperative period. AB - INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) are widely used in treating anemia associated with renal failure. They are also now used perioperatively to reduce the use of allogeneic blood transfusions (ABTs) in patients undergoing surgery with anticipated high blood loss. Although they can reduce the risks associated with ABT and improve quality of life, the use of ESAs is still associated with adverse effects. AREAS COVERED: A narrative review is provided on ESAs and a systematic review has been conducted to examine the current evidence for the efficacy and safety of perioperative ESAs use. A search of PubMed and Medline databases has been performed using a combination of search terms including erythropoietin, perioperative, surgical, safety and efficacy. EXPERT OPINION: Current evidence supports the use of perioperative ESAs to reduce the need for ABT. However, large studies assessing safety in anemic patients with chronic renal disease have found adverse effects including cardiovascular, stroke and thromboembolic events. However, whether these concerns can be conferred onto the surgical population remains to be seen as the perioperative dosing strategies have been more variable in timing, dose and duration in comparison with those used for chronic diseases. Future research needs to address the questions of optimal dosing strategies in order to maximize the positive effects and minimize adverse events. PMID- 24219368 TI - MAPK activation in mature cataract associated with Noonan syndrome. AB - BACKGROUND: Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched palate, and cardiovascular malformation. Its pathological condition is thought to be due to a gain-of-function mutation in the Ras-mitogen activated protein kinase (MAPK) signal transduction pathway. Eyelid abnormalities such as ocular hypertelorism and blepharoptosis are the most commonly observed eye complications. CASE PRESENTATION: We report a case of Noonan syndrome associated with mature cataract that required operation. A 42-year-old man was diagnosed with Noonan syndrome at the age of 1 year. He underwent an eye examination after complaining of decreased visual acuity in the right eye and was diagnosed with mature cataract, which was treated by cataract surgery. There were no intraoperative complications, and the postoperative course was uneventful. Protein analysis of lens capsule and epithelium at capsulorhexis showed MAPK cascade proteins such as ERK and p38MAPK were upregulated. An abnormality in the PTPN11 gene was also observed; a potential mechanism of cataract onset may be that opacity of the lens rapidly progressed due to abnormal activation of the Ras MAPK signal transduction pathway. CONCLUSION: This case highlights the possible association of cataract formation with MAPK cascade protein upregulation in Noonan syndrome. PMID- 24219369 TI - Mouse embryonic stem cells have underdeveloped antiviral mechanisms that can be exploited for the development of mRNA-mediated gene expression strategy. AB - We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type I interferons (IFN) when exposed to viral infection and double stranded RNA. In this study, we extended our investigation and demonstrated that single-stranded RNA and protein-encoding mRNA can induce strong IFN expression and cytotoxicity in fibroblasts and epithelial cells, but none of the effects associated with these antiviral responses were observed in mESCs. Our results provided additional data to support the conclusion that mESCs are intrinsically deficient in antiviral responses. While our findings represent a novel feature of mESCs that in itself is important for understanding innate immunity development, we exploited this property to develop a novel mRNA-mediated gene expression cell model. Direct introduction of synthetic mRNA to express desired genes has been shown as an effective alternative to DNA/viral vector-based gene expression. However, a major biological challenge is that a synthetic mRNA is detected as a viral RNA analog by the host cell, resulting in a series of adverse effects associated with antiviral responses. We demonstrate that the lack of antiviral responses in mESCs effectively avoids this problem. mESCs can tolerate repeated transfection and effectively express proteins from their synthetic mRNA with expected biological functions, as demonstrated by the expression of green fluorescent protein and the transcription factor Etv2. Therefore, mRNA-based gene expression could be developed into a novel ESC differentiation strategy that avoids safety concerns associated with viral/DNA-based vectors in regenerative medicine. PMID- 24219371 TI - Healthier dietary pattern and lower risk of metabolic syndrome in physically active postmenopausal women. AB - OBJECTIVES: To investigate the relationship between habitual physical activity and dietary intake, body composition, metabolic and hormonal variables, and cardiovascular risk factors in postmenopausal women with no evidence of cardiovascular disease. METHODS: In this cross-sectional study, 105 women (mean age: 55.2 +/- 4.9 years) consulting for climacteric symptoms underwent anthropometric and hormonal assessment. Usual dietary intake was assessed with a food frequency questionnaire and habitual physical activity was assessed with a digital pedometer. Participants were classified as physically inactive (<6000 steps daily) or physically active (>=6000 steps daily). RESULTS: Compared to the inactive group, active women had higher protein, total fat, cholesterol, iron, calcium, and the antioxidant micronutrients zinc and selenium intake as well as differences on food groups: higher meat, egg, and whole-dairy intake and lower intake of chips. Active participants also presented lower diastolic blood pressure (p = 0.012), ultrasensitive C-reactive protein (us-CRP; p = 0.011), fasting glucose (p = 0.003), fasting insulin (p = 0.019), and homeostasis model assessment index (p = 0.017). After adjustment for age and time since menopause, the risk for metabolic syndrome increased with physical inactivity (odds ratio [OR] = 3.55, 95% confidence interval [CI], 1.08-11.66), us-CRP (OR = 6.57, 95% CI, 2.20-19.56), and percentage body fat (OR = 5.65, 95% CI, 1.19-28.89). CONCLUSION: Both physical activity and dietary choices may have contributed toward a more favorable cardiovascular profile and lower risk of metabolic syndrome in postmenopausal women. PMID- 24219370 TI - Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial. AB - BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028. PMID- 24219372 TI - Plasma 25-hydroxyvitamin D, hormonal contraceptive use, and cardiometabolic disease risk in an ethnically diverse population of young adults. AB - OBJECTIVES: The relationship between vitamin D and cardiometabolic disease risk across ethnic groups is unclear, and it is not known whether the use of hormonal contraceptives (HCs), which affect vitamin D metabolism and are also associated with cardiometabolic disease risk, modifies this relationship. Our objectives were to determine the prevalence of vitamin D deficiency (plasma 25 hydroxyvitamin D [25(OH)D] < 30 nmol/L) to assess seasonal variation in concentrations of 25(OH)D, and to examine whether 25(OH)D is associated with cardiometabolic biomarkers across ethnic groups and across men, female HC nonusers, and female HC users in an ethnically diverse population of young adults living in Canada. METHODS: The study population consisted of Caucasian, East Asian, and South Asian individuals (n = 1384, 69% female) aged 20-29 years. Participants provided overnight fasting blood samples, from which plasma 25(OH)D and cardiometabolic biomarkers were measured. Vitamin D status distributions were compared using chi(2) tests, and analysis of covariance (ANCOVA) was used to examine seasonal variations in 25(OH)D, as well as the association between 25(OH)D and cardiometabolic biomarkers, across groups. RESULTS: Plasma 25(OH)D concentrations fluctuated seasonally among Caucasians and East Asians and across men, female HC nonusers, and female HC users, but they remained low year-round in South Asians, half of whom were vitamin D deficient. Vitamin D deficiency was associated with higher insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), and homeostasis model assessment (HOMA)-beta among Caucasians and East Asians and among men and female HC nonusers and with higher triglycerides among men only. No biomarkers were associated with 25(OH)D among South Asians and female HC users, although nonsignificant trends were observed for higher markers of glycemic dysregulation in those who were vitamin D deficient in both groups. CONCLUSIONS: Vitamin D deficiency varies between ethnic groups and is particularly high among South Asians, and it is associated with biomarkers of glycemic dysregulation; however, HC use among women may attenuate this association. Given the widespread use of HCs by women throughout the world, a better understanding of the extent to which these medications may modify the relationship between vitamin D and processes related to disease is warranted. PMID- 24219373 TI - Full mini nutritional assessment and prognosis in elderly patients with pulmonary tuberculosis. AB - OBJECTIVE: Malnutrition is observed frequently in elderly patients with pulmonary tuberculosis (TB). Full Mini Nutritional Assessment (full MNA) is a useful method of measuring nutrition status for elderly person. The objective of this study is to examine the relationship between full MNA and the mortality of elderly patients with pulmonary TB. METHODS: We evaluated 53 elderly patients with pulmonary TB. The nutrition risk assessment was carried out using full MNA. RESULTS: A receiver operating characteristic (ROC) curve was generated for further analysis of the prognostic value of full MNA score. The area under the curve was 0.856 (95% confidence interval [CI], 0.751-0.961). We used the maximum Youden index to obtain optimal cutoff values for full MNA score for prognostic assessment in elderly patients with pulmonary TB. For predicting the risk of mortality, the optimal cutoff value for full MNA score was 13.75. Based on this cutoff value, the Cox proportional hazard model was applied to assess the ability of full MNA score < 14 to predict the prognosis of elderly patients with pulmonary TB. Multivariate analysis identified age (hazard ratio [HR] = 1.114, 95% CI, 1.018-1.219, p = 0.019) and full MNA score < 14 (HR = 9.038, 95% CI, 1.064-76.768, p = 0.044) to be significant independent prognostic factors for survival. CONCLUSION: Severe malnutrition, as defined by full MNA score < 14, was a predictor of high mortality. PMID- 24219374 TI - Effects of an iron or iron and vitamin D-fortified flavored skim milk on iron metabolism: a randomized controlled double-blind trial in iron-deficient women. AB - OBJECTIVES: Iron deficiency anemia and vitamin D deficiency are considered global pandemics. The aim of this study was to determine whether the consumption of a dairy product fortified with iron and vitamin D, compared to the equivalent with only added iron, exerts an additional effect on iron metabolism in iron-deficient menstruating women. METHODS: The design was a randomized, placebo-controlled, double-blind, parallel-group trial of 16 weeks' duration. Subjects were randomized into 2 groups that consumed, as part of their usual diet, 500 mL/day of an iron (n = 54) or iron- and vitamin D-fortified (n = 55) flavored skim milk. At baseline and monthly, dietary intake, body weight, and hematological and iron metabolism biomarkers were determined. Serum 25-hydroxyvitamin D was analyzed at baseline and weeks 8 and 16. Data were analyzed by analysis of variance (ANOVA) of repeated measures for time and Time * Group interaction effects. RESULTS: A total of 109 volunteers completed the study. Calcium and iron intakes increased during the intervention (p < 0.001 for both groups). Serum 25-hydroxyvitamin D significantly increased in Fe + D group during the assay (p < 0.001) and at week 16 it was higher compared to the Fe group (p < 0.05). Serum ferritin, serum transferrin, mean corpuscular volume, mean corpuscular hemoglobin, and red blood cell distribution width showed significant time effects but no Time * Group interaction. Higher values of erythrocytes (p = 0.01), hematocrit (p = 0.05), and hemoglobin (p = 0.03) at week 8 were observed in the Fe + D group compared to the Fe group. CONCLUSION: Iron-fortified flavored skim milk does not improve iron status in iron-deficient menstruating women. However, vitamin D fortification slightly enhances erythropoiesis and iron status. PMID- 24219375 TI - Calcium and vitamin D disparities are related to gender, age, race, household income level, and weight classification but not vegetarian status in the United States: Analysis of the NHANES 2001-2008 data set. AB - OBJECTIVE: Adequate calcium and vitamin D intakes are critical during all life cycle stages. This study aimed to characterize usual intakes of calcium and vitamin D from food and dietary supplements in specific subpopulations of Americans so that fortification/enrichment and supplementation efforts may be targeted toward populations who are truly in need. METHODS: The National Cancer Institute method was used to estimate usual intakes of calcium and vitamin D by source and compared usual intakes to the established Dietary Reference Intakes for U.S. residents aged >=4 years using National Health and Nutrition Examination Survey 2001-2002, 2003-2004, 2005-2006, and 2007-2008 data sets. RESULTS: These results showed for the first time that low-income, overweight, and/or obese minority populations may be at greater risk of calcium and vitamin D insufficiency. Children aged 4-8 years were more likely to obtain recommended dairy intakes compared with older children and adults of all ages. Food intakes of calcium decreased with age in adults. Adults who used supplemental calcium showed a lower prevalence of insufficiency. Calcium and vitamin D intakes from food and dietary supplements were not related to vegetarian status. Excessive intakes of calcium and vitamin D above the tolerable upper intake level were low among all studied populations and "overnutrification" was not widely present across these analyses. CONCLUSIONS: Age- and gender-specific supplementation and modest use of fortification with calcium and vitamin D may be warranted for targeting certain subpopulations, particularly older adults, teenagers, minorities, and those who are low income and overweight and/or obese. PRACTICAL APPLICATION: This study aimed to characterize usual intakes of calcium and vitamin D from food and dietary supplements in specific subpopulations of Americans so that fortification/enrichment and supplementation efforts may be better targeted. Low-income, overweight, and/or obese minority populations may be at a greater risk of calcium and vitamin D insufficiency. PMID- 24219376 TI - Immunomodulatory effects of ResistAidTM: A randomized, double-blind, placebo controlled, multidose study. AB - OBJECTIVE: To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. METHODS: This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18 61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. RESULTS: As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. CONCLUSIONS: ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine). PMID- 24219377 TI - A systematic review of multivitamin-multimineral use and cardiovascular disease and cancer incidence and total mortality. AB - Multivitamin-multimineral (MVM) supplements are the most frequently used dietary supplements in the United States, with one third or more of the population using at least one daily. However, the health-related implications of MVM use are unclear. Thus, we systematically reviewed and summarized the prospective studies of MVM supplementation and all-cause and cause-specific mortality, as well as cardiovascular disease (CVD) and cancer incidence, to critically evaluate the current evidence on this topic. We included studies of generally healthy adult populations that evaluated multivitamin (the most commonly used dietary supplement) and/or multimineral supplement use or simultaneous use of 3 or more vitamins and minerals. We did not evaluate individual supplements. A total of 12 cohort studies and 3 primary prevention randomized controlled trials met our inclusion criteria. The majority of the studies were conducted in the United States (n = 11), and the remaining were conducted in European countries (n = 3) and Japan (n = 1). Although between-study methodological variation was present, most relative risks hovered closely around or slightly below the null value. No clear patterns of associations by study country, gender, smoking status, or frequency of use were observed. Based upon the available scientific evidence to date, supplementation with MVMs does not appear to increase all-cause mortality, cancer incidence or mortality, or CVD incidence or mortality and may provide a modest protective benefit. PMID- 24219378 TI - New directions in the prevention of pediatric atherogenesis and obesity. PMID- 24219381 TI - Dual-functionalized PAMAM dendrimers with improved P-glycoprotein inhibition and tight junction modulating effect. AB - This study aims to surface modify poly(amido amine) or PAMAM dendrimers by sequentially grafting poly(ethylene glycol) or PEG and 4-thiobutylamidine (TBA) so as to reduce PAMAM cytotoxicity while improving the ability of PAMAM to modulate P-glycoprotein (P-gp) efflux and tight junction integrity. Conjugation of functional groups was determined by NMR spectroscopy, FT-IR, thiol group quantification and molecular weight estimation. The yield of the dual functionalized dendrimers was >80%. The dual-functionalized dendrimer could significantly reduce PAMAM cytotoxicity to <15% as reflected by LDH release in Caco-2 and MDCK/MDR1 cells after 72 h of exposure. Thiolated dendrimers could increase cellular accumulation and permeation of the P-gp substrate R-123, and such effect could be affected by the extent of PEGylation of the dendrimer. Surface-modified PAMAM dendrimers, either by single or dual functionalization, could better modulate tight junction integrity in comparison with unmodified PAMAM, as demonstrated through immunostaining of the tight junction marker ZO-1, permeation of the model compound Lucifer Yellow (LY) and transepithelial electrical resistance (TEER). Of importance, reversible tight junction modulating effect was only observed in the dual-functionalized dendrimers. Collectively, dual functionalization with PEG and TBA represented a promising approach in altering PAMAM dendrimer surface for potential application in oral drug delivery. PMID- 24219382 TI - Cinderella story: PI4P goes from precursor to key signaling molecule. AB - Phosphatidylinositol lipids are signaling molecules involved in nearly all aspects of cellular regulation. Production of phosphatidylinositol 4-phosphate (PI4P) has long been recognized as one of the first steps in generating poly phosphatidylinositol phosphates involved in actin organization, cell migration, and signal transduction. In addition, progress over the last decade has brought to light independent roles for PI4P in membrane trafficking and lipid homeostasis. Here, we describe recent advances that reveal the breadth of processes regulated by PI4P, the spectrum of PI4P effectors, and the mechanisms of spatiotemporal control that coordinate crosstalk between PI4P and cellular signaling pathways. PMID- 24219383 TI - Silencing of the cell cycle checkpoint gene 14-3-3sigma in basal cell carcinomas correlates with reduced expression of IKK-alpha. AB - BACKGROUND: 14-3-3sigma is down-regulated in a large proportion of basal cell carcinomas (BCC). IkappaB kinase alpha (IKK-alpha), one of the two catalytic subunits of the IKK complex involved in NF-kappaB-activation, also functions as a modulator of epidermal development and differentiation. Down-regulation of IKK alpha causes hyperplasia and promotes skin cancer. IKK-alpha has been found to regulate the expression of 14-3-3sigma by shielding its promoter from hypermethylation and thereby preventing its silencing in mouse keratinocytes. OBJECTIVES: To evaluate the potential role of IKK-alpha in the silencing of 14-3 3sigma in basal cell carcinoma. MATERIALS AND METHODS: Expression of 14-3-3sigma and IKK-alpha was studied by immunohistochemistry in 33 sporadic BCCs and 26 BCCs from patients with basal cell nevus syndrome (BCNS). RESULTS: Marked reduction or absence of 14-3-3sigma was found in 24 (92%) BCCs from BCNS patients, and in 29 (88%) sporadic BCCs. Marked reduction or absence of IKK-alpha was found in 22 (85%) BCCs from patients with BCNS, and in 27 (82%) sporadic BCCs. Expression levels for 14-3-3sigma and IKK-alpha correlated positively in 92% of BCCs from BCNS patients, and in 85% of sporadic BCCs. CONCLUSIONS: Our findings suggest that down-regulation of IKK-alpha is required for 14-3-3sigma promoter methylation and silencing in the pathogenesis of BCC. Besides, our observation that 14-3-3sigma silencing is also frequently found in BCC from patients with BCNS suggests a possible link between the sonic hedgehog/patched and 14-3 3sigma/IKK-alpha pathways. PMID- 24219384 TI - Sexual dysfunction in male patients with multiple sclerosis: a need for counseling! AB - Sexuality and sexual health are significant factors in determining the quality of life (QoL). Multiple sclerosis (MS) is one of the most serious causes of neurological disability in young adults, therefore it can considerably reduce sexuality. Physical and cognitive symptoms of MS as well as mental and psycho social issues can directly affect sexual life and body representation, causing reduced libido and self-esteem. Male patients with MS frequently develop sexual dysfunction (SD) as a result of their neurological impairment: in fact physical, psychological and neuropsychological changes indirectly interfere in the sexual response. Thus, MS physicians' greater concern on SD has led to the enhancement of diagnostic and therapeutic diagnoses on neurogenic SD. Given the increasing number of people coping with MS, a more effective focus on MS-related problems, including SD, is absolutely essential to provide the patients and their partner with the necessary information to achieve a better sexual health and consequently improve their QoL. This review aims to investigate the epidemiology and pathophysiology of SD in male patients, provide an insight into multidisciplinary diagnostic and therapeutic approaches, and focus on the need of proper counseling. PMID- 24219385 TI - Abeta-induced microglial cell activation is inhibited by baicalin through the JAK2/STAT3 signaling pathway. AB - Baicalin has shown multiple neuroprotective biological activities, including antiapoptotic and anti-inflammatory functions in neurodegeneration diseases. However, whether baicalin can regulate Abeta-induced microglial activation or inhibit inflammatory cytokine secretion has not been confirmed. We demonstrated that baicalin can inhibit beta amyloid peptides (Abeta42)-induced BV2 microglial cell proliferation, reduce the expression of CD11b, decrease chemotactic ability of BV2 cells and significantly inhibit the secretion of IL-6, TNF-alpha and NO. Moreover, baicalin pretreatment can effectively inhibit Abeta-induced phosphorylation of JAK2 and STAT3. Baicalin can inhibit Abeta-induced microglial cell activation by regulating the JAK2/STAT3 signaling pathway in AD transgenic mice. The modulation of microglial proliferation, activation and secretion by baicalin could be a promising therapeutic option for the treatment of Alzheimer's disease. PMID- 24219386 TI - Change of Nrf2 expression in rat hippocampus in a model of chronic cerebral hypoperfusion. AB - Chronic cerebral hypoperfusion (CCH) is common in vascular dementia and Alzheimer's disease. CCH-related oxidative damage plays a significant role in the development of cognitive impairment. Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediates activation of the antioxidant responsive element (ARE)-related gene expression, which is crucial to the endogenous antioxidative system. In this case, we used permanent bilateral occlusion of common carotid arteries (2VO) to mimic CCH. The expression of Nrf2 in different regions of the hippocampus as well as the ability of nuclear Nrf2 and ARE binding have been examined. A phenomenon has been observed that the DNA binding activities were down-regulated. Interestingly, the expression of Nrf2 rose significantly in most regions of rat hippocampus within three weeks after the 2VO surgery. The mismatch might attribute to Nrf2 dysfunction and compensatory synthesis. A conclusion can be drawn that Nrf2 dysfunction is an important factor as a cause of CCH-induced oxidative damage and Nrf2 can be treated as a promising target to alleviate oxidative damage, even cognitive impairment caused by CCH. PMID- 24219387 TI - The ADA examines student debt. PMID- 24219388 TI - These pretzels are going to make me thirsty tomorrow: differential development of hot and cool episodic foresight in early childhood? AB - The current study examined 3- and 7-year-olds' performance on two types of episodic foresight tasks: A task that required 'cool' reasoning processes about the use of objects in future situations and a task that required 'hot' processes to inhibit a salient current physiological state in order to reason accurately about a future state. Results revealed that 7-year-olds outperformed 3-year-olds on the episodic foresight task that involved cool processes, but did not show age differences in performance on the task that involved hot processes. In fact, both 3- and 7-year-olds performed equally poorly on the task that required predicting a future physiological state that was in conflict with their current state. Further, performance on the two tasks was unrelated. We discuss the results in terms of differing developmental trajectories for episodic foresight tasks that differentially rely on hot and cool processes and the universal difficulties humans have with predicting later outcomes that conflict with current motivational states. PMID- 24219389 TI - Evaluation of carotid intima-media thickness and aortic elasticity in patients with nondipper hypertension. AB - BACKGROUND: The relationship between cardiovascular diseases and the diurnal blood pressure (BP) rhythm was researched in many studies. It has been demonstrated that the nondipping pattern has been associated with target organ damage and worsened cardiovascular outcomes. The aim of our study was to assess the relationship between aortic elasticity parameters and carotid intima-media thickness (CIMT) and diastolic dysfunction in terms of "dipper" and "nondipper" hypertension subtypes. METHODS: A total of 60 hypertensive patients without known coronary heart disease were recruited to our study. All patients were classified as "dipper" or "nondipper" after ambulatory BP follow-up. Patients' left ventricular (LV) systolic and diastolic functions were assessed with transthoracic echocardiography. Ascending aorta diameters and CIMT were measured by ultrasonography and the elasticity parameters of aorta were calculated by using relevant formula. RESULTS: There were no significant differences between the groups with respect to demographic, biochemical data, and cardiovascular risk factors. Aortic stiffness was significantly increased in nondippers, whereas aortic strain and distensibility were significantly decreased (P = 0.005, P = 0.005, and P = 0.024, respectively). Carotid artery IMT was significantly increased in nondippers compared to dippers (P = 0.013). A significant correlation was noted between CIMT and mean BP. No significant difference was detected between 2 groups in terms of LV hypertrophy and diastolic dysfunction. CONCLUSION: In our study, we showed that impairment of aortic elasticity parameters and increase in CIMT as a predictor of end organ damage were more often in the nondipper hypertensive patients. PMID- 24219390 TI - Distribution patterns of Ohio stoneflies, with an emphasis on rare and uncommon species. AB - Presently, 102 stonefly species (Plecoptera) have been reported from Ohio. All 9 Nearctic families are represented. Over 90% of the fauna exhibit a combination of broad Nearctic-widespread, eastern Nearctic-widespread, Appalachian, and eastern Nearctic-unglaciated distributions. In contrast, only 2 species display a central Nearctic-Prairie distribution. Seven species of Perlidae are likely no longer present (Acroneuria evoluta Klapalek, A. perplexa Frison, Attaneuria ruralis (Hagen), and Neoperla mainensis Banks) or have experienced marked range reductions (Acroneuria abnormis (Newman), A. frisoni Stark and Brown, and A. filicis Frison). Another nearly 31% of the fauna (32 species) are rare, uncommon, or have highly-limited distributions within the state. Twelve of these species have Appalachian distributions, and an additional 8 have eastern Nearctic unglaciated distributions. The distributional status for each of the 32 rare/uncommon species is discussed. PMID- 24219391 TI - In the ear of the beholder: how age shapes emotion processing in nonverbal vocalizations. AB - It is well established that emotion recognition of facial expressions declines with age, but evidence for age-related differences in vocal emotions is more limited. This is especially true for nonverbal vocalizations such as laughter, sobs, or sighs. In this study, 43 younger adults (M = 22 years) and 43 older ones (M = 61.4 years) provided multiple emotion ratings of nonverbal emotional vocalizations. Contrasting with previous research, which often includes only one positive emotion (happiness) versus several negative ones, we examined 4 positive and 4 negative emotions: achievement/triumph, amusement, pleasure, relief, anger, disgust, fear, and sadness. We controlled for hearing loss and assessed general cognitive decline, cognitive control, verbal intelligence, working memory, current affect, emotion regulation, and personality. Older adults were less sensitive than younger ones to the intended vocal emotions, as indicated by decrements in ratings on the intended emotion scales and accuracy. These effects were similar for positive and negative emotions, and they were independent of age related differences in cognitive, affective, and personality measures. Regression analyses revealed that younger and older participants' responses could be predicted from the acoustic properties of the temporal, intensity, fundamental frequency, and spectral profile of the vocalizations. The two groups were similarly efficient in using the acoustic cues, but there were differences in the patterns of emotion-specific predictors. This study suggests that ageing produces specific changes on the processing of nonverbal vocalizations. That decrements were not attenuated for positive emotions indicates that they cannot be explained by a positivity effect in older adults. PMID- 24219392 TI - Sequential unfolding of appraisals: EEG evidence for the interaction of novelty and pleasantness. AB - An important question in emotion research is what elicits emotions and causes variations in their quality and intensity. Appraisal theories propose a cognitive process through which stimuli are evaluated on a number of different criteria. The combination of results on these criteria determines which specific emotion is elicited. In the present study, we addressed several questions regarding the mechanisms underlying this process, specifically whether appraisal criteria are processed (a) in a fixed sequence, (b) independently of each other, and (c) by different neural structures or circuits. Two appraisal criteria, stimulus novelty and pleasantness, were manipulated with a 3-stimulus oddball paradigm with affective pictures. Electroencephalographic (EEG) markers for the appraisal processes were distinguished using a spatiotemporal clustering analysis. Consistent with theories that assume a fixed sequence of the appraisal process, the analyses revealed early effects of novelty on global field power and the topographical pattern of EEG activity, followed in time by effects involving pleasantness. Moreover, both measures showed significant interactions of novelty and pleasantness in late processing stages (650 ms-800 ms), indicating that the processing of pleasantness depends on the preceding appraisal of novelty. The results of spatiotemporal clustering suggest that the late processing of highly relevant stimuli is not based on a single mechanism, but consists of the initial activation of distinct neural processes to evaluate novel stimuli, followed by activation of different neural mechanisms for the combined evaluation of both novel and highly valenced (i.e., unpleasant or pleasant) stimuli (a distinction that is not apparent in conventional event-related potential measures). PMID- 24219393 TI - Emotional intelligence predicts success in medical school. AB - Accumulating evidence suggests that effective communication and interpersonal sensitivity during interactions between doctors and patients impact therapeutic outcomes. There is an important need to identify predictors of these behaviors, because traditional tests used in medical admissions offer limited predictions of "bedside manners" in medical practice. This study examined whether emotional intelligence would predict the performance of 367 medical students in medical school courses on communication and interpersonal sensitivity. One of the dimensions of emotional intelligence, the ability to regulate emotions, predicted performance in courses on communication and interpersonal sensitivity over the next 3 years of medical school, over and above cognitive ability and conscientiousness. Emotional intelligence did not predict performance on courses on medical subject domains. The results suggest that medical schools may better predict who will communicate effectively and show interpersonal sensitivity if they include measures of emotional intelligence in their admission systems. PMID- 24219394 TI - The power of emotion versus the power of suggestion: memory for emotional events in the misinformation paradigm. AB - Research has shown that emotional events are remembered better than neutral events, but might also elicit an increase in false memories. The present study was designed to disentangle the influences of valence and arousal on event memory in the misinformation paradigm. Participants were shown six types of photographs (positive with high/low arousal, negative with high/low arousal, ambiguous, neutral), after which half of them were exposed to misleading information. A recognition test assessed memory for both correct and false central and peripheral details. Negative and ambiguous events elicited fewer correct and more false memories for peripheral details than positive and neutral events, regardless of previous exposure to misinformation. Arousal improved memory for correct central details, and both negative valence and arousal inhibited control participants' tendency to endorse false central details. The power of emotion was overruled by the power of suggestion, however, as the latter effect disappeared with previous exposure to misinformation. Results are discussed in the light of earlier research on emotion and cognition, recent motivational theories, and implications for forensic practice. PMID- 24219395 TI - The influence of social comparison on cognitive bias modification and emotional vulnerability. AB - The Cognitive Bias Modification (CBM) paradigm was devised to test predictions that cognitive biases have a causal influence on emotional status. Increasingly, however, researchers are testing the potential clinical applications of CBM. Although generally successful in reducing emotional vulnerability in clinical populations, the impact of CBM interventions has been somewhat variable. The aim of the current experiment was to investigate whether social comparison processing might be an important moderator of CBM. Healthy participants were presented with 80 valenced scenarios devised to induce a positive or negative interpretative bias. Critically, participants answered a series of questions designed to establish whether they assimilated or contrasted themselves with the valenced descriptions. The induction of an interpretation bias that was congruent with the valence of the training scenarios was successful only for participants who tended to assimilate the valenced scenarios, and not for those participants who tended to evaluate themselves against the scenarios. Furthermore, the predicted influence of CBM on emotional outcomes occurred only for those who had an assimilative rather than evaluative orientation toward CBM training material. Of key importance, results indicated that "evaluators" showed increased emotional vulnerability following positive CBM training. This result has both theoretical and clinical implications in suggesting that the success of CBM is dependent upon the way in which participants socially compare themselves with CBM training material. PMID- 24219396 TI - Fight fire with fire: the effect of perceived anger on punitive intuitions. AB - The human ability to "mind-read" is fundamental in social interaction (e.g., contributing to the experience of empathy). The present research tests the hypothesis that perceiving anger in others on the basis of facial cues is sufficient to elicit very rapid punitive responses toward crime. The results suggest that individuals are faster to harshly punish criminals who appear to be angry, and that this effect emerges early in the decision-making process. Black criminals receive quicker punitive responses, but the effect of ethnicity is weakened at high levels of perceived anger. The results are discussed in terms of associative processes linking anger to punishment, the human ability to simulate and experience others' emotional responses, and the role of anger in eliciting hostile aggression. The findings also have important policy implications, as they suggest that drumming up anger toward crime could engender punitive intuitions. PMID- 24219397 TI - Human amygdala response to dynamic facial expressions of positive and negative surprise. AB - Although brain imaging evidence accumulates to suggest that the amygdala plays a key role in the processing of novel stimuli, only little is known about its role in processing expressed novelty conveyed by surprised faces, and even less about possible interactive encoding of novelty and valence. Those investigations that have already probed human amygdala involvement in the processing of surprised facial expressions either used static pictures displaying negative surprise (as contained in fear) or "neutral" surprise, and manipulated valence by contextually priming or subjectively associating static surprise with either negative or positive information. Therefore, it still remains unresolved how the human amygdala differentially processes dynamic surprised facial expressions displaying either positive or negative surprise. Here, we created new artificial dynamic 3 dimensional facial expressions conveying surprise with an intrinsic positive (wonderment) or negative (fear) connotation, but also intrinsic positive (joy) or negative (anxiety) emotions not containing any surprise, in addition to neutral facial displays either containing ("typical surprise" expression) or not containing ("neutral") surprise. Results showed heightened amygdala activity to faces containing positive (vs. negative) surprise, which may either correspond to a specific wonderment effect as such, or to the computation of a negative expected value prediction error. Findings are discussed in the light of data obtained from a closely matched nonsocial lottery task, which revealed overlapping activity within the left amygdala to unexpected positive outcomes. PMID- 24219398 TI - Are narcissists hardy or vulnerable? The role of narcissism in the production of stress-related biomarkers in response to emotional distress. AB - Does narcissism provide a source of hardiness or vulnerability in the face of adversity? The present research addressed this question by testing whether narcissism is associated with increased physiological reactivity to emotional distress, among women. Drawing on the "fragile-ego" account, we predicted that narcissists would show a heightened physiological stress profile in response to everyday frustrations. Results supported this prediction; across a 3-day period, highly narcissistic individuals showed elevated output of 2 biomarkers of stress- cortisol and alpha--amylase-to the extent that they experienced negative emotions. In contrast, among those low in narcissism there was no association between these biomarkers and emotions. These findings suggest that narcissists' stress-response systems are particularly sensitive to everyday negative emotions, consistent with the notion that narcissism comes with physiological costs. PMID- 24219399 TI - Aiming for the stomach and hitting the heart: dissociable triggers and sources for disgust reactions. AB - Disgust reactions can be elicited using stimuli that engender orogastric rejection (e.g., pus and vomit; core disgust stimuli) but also using images of bloody injuries or medical procedures (e.g., surgeries; blood [body] boundary violation [B-BV] disgust stimuli). These two types of disgust reaction are presumed to be connected by a common evolutionary function of avoiding either food- or blood-borne contaminants. However, reactions to bloody injuries are typically conflated with reactions to the potential pain being experienced by the victim. This may explain why the two forms of "disgust", although similarly communicated (through self-report and facial expressions), evince different patterns of physiological reactivity. Therefore, we tested whether the communicative similarities and physiological dissimilarities would hold when markers of potential contamination in the latter category are removed, leaving only painful injuries that lack blood or explicit body-envelope violations. Participants viewed films that depicted imagery associated with (a) core disgust, (b) painful injuries, or (c) neutral scenes while we measured facial, cardiovascular, and gastric reactivity. Whereas communicative measures (self report and facial muscles) suggested that participants experienced increased disgust for core disgust and painful injuries, peripheral physiology dissociated the two: core disgust decreased normal gastric activity and painful-injury disgust decelerated heart rate and increased heart rate variability. These findings suggest that expressions of disgust toward bodily injuries may reflect a fundamentally different affective response than those evoked by core disgust and that this (cardiovascularly mediated) response may in fact be more closely tied to pain perceptions (or empathy) rather than contaminant-laden stimuli. PMID- 24219400 TI - Excellent outcome after repeated changes of tyrosine kinase inhibitor therapy for chronic myeloid leukaemia in complete cytogenetic response due to minor side effects. PMID- 24219401 TI - Accumulated lipids rather than the rigid cell walls impede the extraction of genetic materials for effective colony PCRs in Chlorella vulgaris. AB - BACKGROUND: Failure of colony PCRs in green microalga Chlorella vulgaris is typically attributed to the difficulty in disrupting its notoriously rigid cell walls for releasing the genetic materials and therefore the development of an effective colony PCR procedure in C. vulgaris presents a challenge. RESULTS: Here we identified that colony PCR results were significantly affected by the accumulated lipids rather than the rigid cell walls of C. vulgaris. The higher lipids accumulated in C. vulgaris negatively affects the effective amplification by DNA polymerase. Based on these findings, we established a simple and extremely effective colony PCR procedure in C. vulgaris. By simply pipetting/votexing the pellets of C. vulgaris in 10 ul of either TE (10 mM Tris/1 mM EDTA) or 0.2% SDS buffer at room temperature, followed by the addition of 10 ul of either hexane or Phenol:Chloroform:Isoamyl Alcohol in the same PCR tube for extraction. The resulting aqueous phase was readily PCR-amplified as genomic DNA templates as demonstrated by successful amplification of the nuclear 18S rRNA and the chloroplast rbcL gene. This colony PCR protocol is effective and robust in C. vulgaris and also demonstrates its effectiveness in other Chlorella species. CONCLUSIONS: The accumulated lipids rather than the rigid cell walls of C. vulgaris significantly impede the extraction of genetic materials and subsequently the effective colony PCRs. The finding has the potential to aid the isolation of high-quality total RNAs and mRNAs for transcriptomic studies in addition to the genomic DNA isolation in Chlorella. PMID- 24219402 TI - Spectroscopic identification of binary and ternary surface complexes of Np(V) on gibbsite. AB - For the first time, detailed molecular information on the Np(V) sorption species on amorphous Al(OH)3 and crystalline gibbsite was obtained by in situ time resolved Attenuated Total Reflection Fourier-Transform Infrared (ATR FT-IR) and Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. The results consistently demonstrate the formation of mononuclear inner sphere complexes of the NpO2(+) ion irrespective of the prevailing atmospheric condition. The impact of the presence of atmospheric equivalent added carbonate on the speciation in solution and on the surfaces becomes evident from vibrational data. While the 1:1 aqueous carbonato species (NpO2CO3(-)) was found to become predominant in the circumneutral pH range, it is most likely that this species is sorbed onto the gibbsite surface as a ternary inner sphere surface complex where the NpO2(+) moiety is directly coordinated to the functional groups of the gibbsite's surface. These findings are corroborated by results obtained from EXAFS spectroscopy providing further evidence for a bidentate coordination of the Np(V) ion on amorphous Al(OH)3. The identification of the Np(V) surface species on gibbsite constitutes a basic finding for a comprehensive description of the dissemination of neptunium in groundwater systems. PMID- 24219403 TI - Computational modeling of an epidermal growth factor receptor single-mutation resistance to cetuximab in colorectal cancer treatment. AB - Extracellular S468R mutation of the epidermal growth factor receptor (EGFR) was recently identified as the cause of resistance to cetuximab, a widely used drug in colorectal cancer treatment. Here, we have determined the binding free energies of cetuximab's Fab V(H)-V(L) domains and endogenous EGF ligand to wild type and S468R EGFR by high-throughput molecular dynamics. This work provides a possible mechanism of resistance in terms of increased competition, an hypothesis that can be further validated experimentally. PMID- 24219404 TI - Global estimates of the burden of injury and illness at work in 2012. AB - This article reviews the present indicators, trends, and recent solutions and strategies to tackle major global and country problems in safety and health at work. The article is based on the Yant Award Lecture of the American Industrial Hygiene Association (AIHA) at its 2013 Congress. We reviewed employment figures, mortality rates, occupational burden of disease and injuries, reported accidents, surveys on self-reported occupational illnesses and injuries, attributable fractions, national economic cost estimates of work-related injuries and ill health, and the most recent information on the problems from published papers, documents, and electronic data sources of international and regional organizations, in particular the International Labor Organization (ILO), World Health Organization (WHO), and European Union (EU), institutions, agencies, and public websites. We identified and analyzed successful solutions, programs, and strategies to reduce the work-related negative outcomes at various levels. Work related illnesses that have a long latency period and are linked to ageing are clearly on the increase, while the number of occupational injuries has gone down in industrialized countries thanks to both better prevention and structural changes. We have estimated that globally there are 2.3 million deaths annually for reasons attributed to work. The biggest component is linked to work-related diseases, 2.0 million, and 0.3 million linked to occupational injuries. However, the division of these two factors varies depending on the level of development. In industrialized countries the share of deaths caused by occupational injuries and work-related communicable diseases is very low while non-communicable diseases are the overwhelming causes in those countries. Economic costs of work related injury and illness vary between 1.8 and 6.0% of GDP in country estimates, the average being 4% according to the ILO. Singapore's economic costs were estimated to be equivalent to 3.2% of GDP based on a preliminary study. If economic losses would take into account involuntary early retirement then costs may be considerably higher, for example, in Finland up to 15% of GDP, while this estimate covers various disorders where work and working conditions may be just one factor of many or where work may aggravate the disease, injury, or disorders, such as traffic injuries, mental disorders, alcoholism, and genetically induced problems. Workplace health promotion, services, and safety and health management, however, may have a major preventive impact on those as well. Leadership and management at all levels, and engagement of workers are key issues in changing the workplace culture. Vision Zero is a useful concept and philosophy in gradually eliminating any harm at work. Legal and enforcement measures that themselves support companies and organizations need to be supplemented with economic justification and convincing arguments to reduce corner-cutting in risk management, and to avoid short- and long-term disabilities, premature retirement, and corporate closures due to mismanagement and poor and unsustainable work life. We consider that a new paradigm is needed where good work is not just considered a daily activity. We need to foster stable conditions and circumstances and sustainable work life where the objective is to maintain your health and work ability beyond the legal retirement age. We need safe and healthy work, for life. PMID- 24219405 TI - Children, Hunger, and Poverty. PMID- 24219406 TI - Antimicrobial activity and chemical analysis of Microlicia hatschbachii Wurdack (Melastomataceae) extract. AB - Aerial parts of Microlicia hatschbachii were extracted with hexane, and the extract was evaluated for antimicrobial activity by a broth dilution method. After phytochemical procedures: GC-MS identified aliphatic alkanes, carboxylic acids and methyl esters of long-chain fatty acids; and two diterpenoids [labd 8(17)-en-15-oic acid and labd-8(17),13-dien-15-oic acid] were identified by (1)H and (13)C NMR. The antimicrobial activity of the hexane extract could be attributed to the presence of labdanes. This identification is the first reported occurrence of labdane diterpenes in the Melastomataceae family. PMID- 24219407 TI - Drug delivery techniques for treating age-related macular degeneration. AB - INTRODUCTION: Currently, the standard therapy for neovascular age-related macular degeneration involves the use of anti-vascular endothelial growth factor (VEGF) drugs, which are delivered by repeated office-based intravitreal injections. This treatment is generally very effective in stabilizing or improving vision, although repeated injections create a burden for patients, family members and physicians. In addition, the cumulative risks of endophthalmitis and other complications increase with the number of injections. AREAS COVERED: In the clinic, much attention is focused on the relative efficacies of the three major anti-VEGF medications (bevacizumab, ranibizumab and aflibercept) as well as the most popular re-injection regimens (monthly, as-needed and treat-and-extend). In theory, intravitreal anti-VEGF drug delivery with sustained-release devices would offer similar visual results with fewer required re-injections. Various approaches have been studied, including noninvasive techniques, intraocular implants and colloidal carriers, such as liposomes, microparticles and nanoparticles. EXPERT OPINION: Despite its theoretical appeal, sustained-release drug delivery will not replace current techniques unless it offers one or more advantages in efficacy, safety, convenience or cost. Currently, many patients maintain stable vision with intravitreal injections at intervals of 2 months or longer, so sustained-release techniques will have to lengthen these intervals substantially to become widely accepted. As we continue to collect data from clinical trials, the role of sustained-release techniques will become better defined. PMID- 24219409 TI - Statin use and peripheral sensory perception: a pilot study. AB - OBJECTIVES: Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins. METHODS: Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer. RESULTS: There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183). CONCLUSION: This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations. PMID- 24219412 TI - Risk factors and comorbidities in the preclinical stages of chronic obstructive pulmonary disease. AB - RATIONALE: There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD). OBJECTIVES: This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening. METHODS: Sixty subjects with preclinical COPD (63 +/- 6 yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 +/- 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 +/- 6 yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively. MEASUREMENTS AND MAIN RESULTS: The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities. CONCLUSIONS: Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT 01314807). PMID- 24219410 TI - Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression. AB - BACKGROUND: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions. METHODS/DESIGN: To improve understanding of the combined roles of 5 HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression. STUDY ELIGIBILITY CRITERIA: Our goal is to invite all datasets, published or unpublished, with 5 HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias. DATA SOURCES: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results. DISCUSSION: Variation in 5 HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion. PMID- 24219413 TI - Use of eggs derived from the interspecific charr hybrids to induce androgenetic development of the brook charr (Salvelinus fontinalis Mitchill 1814). AB - Although, brook charr (Salvelinus fontinalis Mitchill 1814) and Arctic charr (Salvelinus alpinus Linnaeus 1758) are able to cross and give fertile offspring, their androgenetic nucleocytoplasmic hybrids are not viable. To overcome incompatibility between the egg cytoplasm of one charr species and the sperm nucleus of another charr species, application of F1 interspecific hybrids as egg donors for the purpose of androgenesis has been proposed. Here, androgenetic development of the brook charr was successfully induced in the brook charr eggs and the eggs derived from the reciprocal brook charr * Arctic charr F1 hybrids. A working androgenesis protocol included inactivation of the maternal nuclear DNA achieved by irradiation of the eggs with 420 Gy of X-rays, insemination of such treated eggs with the haploid sperm cells and exposition of the haploid androgenetic zygotes to the high hydrostatic pressure shock (51.711 MPa for 4 min) applied 420 min after insemination. Androgenetic larvae that hatched from the brook charr and the hybrid eggs were shown to be homozygous brook charr individuals. Androgenetic individuals exhibited 84 chromosomes and 100 chromosome arms (FN), values characteristic for the brook charr diploid cells. Strategy hybridize first than induce androgenesis should be tested in order to provide androgenetic offspring in other salmonids that are able to cross and produce fertile offspring. PMID- 24219411 TI - Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein. AB - Human P-glycoprotein (P-gp) controls drugs bioavailability by pumping structurally unrelated drugs out of cells. The X-ray structure of the mouse P-gp ortholog has been solved, with two SSS enantiomers or one RRR enantiomer of the selenohexapeptide inhibitor QZ59, found within the putative drug-binding pocket (Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL et al. (2009). Science 323, 1718-1722). This offered the first opportunity to localize the well-known H and R drug-binding sites with respect to the QZ59 inhibition mechanisms of Hoechst 33342 and daunorubicin transports, characterized here in cellulo. We found that QZ59-SSS competes efficiently with both substrates, with K(I,app) values of 0.15 and 0.3 MUM, which are 13 and 2 times lower, respectively, than the corresponding K(m,app) values. In contrast, QZ59-RRR non-competitively inhibited daunorubicin transport with moderate efficacy (K(I,app) = 1.9 MUM); it also displayed a mixed-type inhibition of the Hoechst 33342 transport, resulting from a main non-competitive tendency (K(i2,app) = 1.6 MUM) and a limited competitive tendency (K(i1,app) = 5 MUM). These results suggest a positional overlap of QZ59 and drugs binding sites: full for the SSS enantiomer and partial for the RRR enantiomer. Crystal structure analysis suggests that the H site overlaps both QZ59-SSS locations while the R site overlaps the most embedded location. PMID- 24219414 TI - Accuracy of Quantitative Computed Tomography Bone Mineral Density Measurements in Mandibles: A Cadaveric Study. AB - PURPOSE: The aim was to investigate the accuracy of quantitative computed tomography bone mineral density (BMD) measurements in mandibles, comparing measured BMD with calibrated BMD. MATERIALS AND METHODS: Seventy mandibles from adult cadavers were used. Twenty tomographic cuts were made in each mandible. In each tomographic cut, a region of interest was located, and the bone density was measured in Hounsfield unit (HU). A polymethyl methacrylate phantom containing four inserts of different predetermined densities (hydroxyapatite 100, 200, 500, and 700 mg/cm(3) ) was used to calculate calibrated bone density. Correlation between measured and calibrated bone densities was calculated. RESULTS: Mean total correlation between measured and calibrated BMD in the 20 sagittal tomography cuts showed almost perfect positive correlation (r = 0.998, p < .001). However, when average BMD measurements in HU were compared, the measured total BMD (in the 20 sagittal tomography cuts studied) was 54.99 +/- 421.59, whereas the total calibrated BMD was 49.28 +/- 364.95, with statistically significant difference (p = .001). CONCLUSIONS: There are discrepancies between measured and calibrated BMD; in this sense, a calibrated bone phantom with a predetermined mineral density should be used to determine the exact BMD before dental implants surgery. PMID- 24219415 TI - Health psychology special section on disparities in pain. AB - In recognition of the importance of addressing health disparities and to encourage research, Health Psychology has called for manuscripts that reflect the breadth of issues related to health disparities. The section on Pain and Disparities in this present issue is part of a series that has included sections on infectious disease and cancer and will continue with a section in 2014 on disparities in genomic medicine. Because disparities in pain and pain care are the result of multiple and dynamic influences, explaining how racial group differences are manifested and perpetuated remains challenging. In this section, two studies focus on patient characteristics that might explain pain disparities. These two studies can be used to underscore the point that knowledge about, and sensitivity to, cultural issues should be an integral part of the pain curriculum of health professionals. PMID- 24219417 TI - Exploring pain processing differences in Native Americans. AB - OBJECTIVE: Several chronic pain conditions are more prevalent in Native Americans than in any other group in the United States; however, little has been done to identify factors contributing to this disparity. The study presented here was designed to examine whether there were pain processing differences in Native Americans relative to non-Hispanic White controls. METHODS: Participants were healthy, pain-free Native Americans (n = 22, 8 females) and non-Hispanic Whites (n = 20, 7 females). Pain processing was assessed from electric pain threshold/tolerance, ischemia pain threshold/tolerance, nociceptive flexion reflex threshold (NFR; an electrophysiological measure of spinal nociception), pain ratings of suprathreshold electric stimuli, and temporal summation of pain and NFR (an electrophysiological measure of spinal cord sensitization). The institutional review board approved all procedures. RESULTS: Compared to non Hispanic Whites, Native Americans had dampened pain perception (higher ischemia pain tolerance, higher electric pain threshold, lower ratings of electric stimuli). Additionally, temporal summation of NFR was reduced in Native Americans, suggesting sensitization was reduced at the spinal level. CONCLUSIONS: Findings suggest Native Americans have dampened pain and pain signaling, perhaps due to overactivation of descending pain inhibition mechanisms. Given research indicating that other ethnic groups at risk for chronic pain (e.g., African Americans) show enhanced pain and enhanced central sensitization on experimental pain measures, chronic pain risk could be different for Native Americans, thus emphasizing the need for different treatment interventions. PMID- 24219416 TI - Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis. AB - OBJECTIVE: Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic Whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. METHOD: One-hundred and 30 (52% African American, 48% non-Hispanic White) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. RESULTS: African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared with non-Hispanic Whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic Whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group. CONCLUSION: These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli. PMID- 24219419 TI - Experimental investigations into astrophysically relevant ionic reactions. PMID- 24219418 TI - Study of the complexation of oxacillin in 1-(4-carbomethoxypyrrolidone) terminated PAMAM dendrimers. AB - The complexation of oxacillin to three generations of 1-(4 carbomethoxypyrrolidone)-terminated PAMAM dendrimers was studied with NMR in CD3OD and CDCl3. The stochiometries, which were determined from Job plots, were found to be both solvent- and generation-dependent. The dissociation constants (K(d)) and Gibbs energies for complexation of oxacillin into the 1-(4 carbomethoxypyrrolidone)-terminated PAMAM dendrimer hosts were determined by (1)H NMR titrations and showed weaker binding of oxacillin upon increasing the size (generation) of the dendrimer. PMID- 24219420 TI - The role of emotion in global warming policy support and opposition. AB - Prior research has found that affect and affective imagery strongly influence public support for global warming. This article extends this literature by exploring the separate influence of discrete emotions. Utilizing a nationally representative survey in the United States, this study found that discrete emotions were stronger predictors of global warming policy support than cultural worldviews, negative affect, image associations, or sociodemographic variables. In particular, worry, interest, and hope were strongly associated with increased policy support. The results contribute to experiential theories of risk information processing and suggest that discrete emotions play a significant role in public support for climate change policy. Implications for climate change communication are also discussed. PMID- 24219421 TI - Secondhand smoke exposure and urine cotinine concentrations by occupation among Korean workers: results from the 2008 Korea National Survey for Environmental Pollutants in the Human Body. AB - This study aimed to estimate the status of secondhand smoke (SHS) exposure through urine cotinine analysis among nonsmoking workers in Korea and to analyze factors affecting urine cotinine concentrations. Data were based on "The 2008 Korea National Survey for Environmental Pollutants in the Human Body," a cross sectional study of the National Institute of Environmental Research of Korea. We selected 1448 nonsmoking adult workers from 200 localities to participate in this survey. Urine cotinine concentrations were analyzed using a gas chromatograph mass selective detector. We calculated separate covariate-adjusted geometric means for socio-demographic variables for males, females, and total subjects by analysis of covariance (ANCOVA). Statistical analyses were performed using SPSS version 18.0 (SPSS Inc., Chicago, Ill.). The prevalence of self-reported exposure to SHS was 36.9%. The geometric mean (95% confidence interval) of urine cotinine concentrations among all participants was 16.50 (14.48-18.80) MUg/L. Gender, living area, education, and SHS exposure showed significant differences in urine cotinine concentrations. The urine cotinine concentrations of farmworkers and blue-collar workers such as skilled agricultural, forestry, and fishery workers, and elementary occupations were higher than those of white-collar workers such as clerical support workers, technicians, and associate professionals. Such a high proportion of the population having high urine cotinine levels indicates widespread exposure to SHS among nonsmoking workers in Korea. Furthermore, the urine cotinine levels among nonsmoking workers exposed to SHS varied by occupation. The measured urine cotinine concentration is suggested to be a valuable indication of SHS exposure in Korea. PMID- 24219423 TI - P2X7 receptor-Pannexin1 interaction mediates stress-induced interleukin-1 beta expression in human periodontal ligament cells. AB - BACKGROUND AND OBJECTIVE: Pannexin 1 (Panx1) has been found to form nonjunctional hemichannels. It is also proposed to combine with the P2X7 receptor, forming a complex involved in adenosine triphosphate (ATP)-induced interleukin-1beta (IL 1beta) release in macrophages. Previously, we reported that mechanical stress induced IL-1beta expression via the ATP/P2X7 receptor-dependent pathway in human periodontal ligament (HPDL) cells and that ATP was released through the connexin 43 (Cx43) hemichannel. In the present work, we examined the role of Panx1 in stress-induced IL-1beta induction in HPDL cells. MATERIAL AND METHODS: Cultured HPDL cells were treated with compressive loading or ATP to stimulate IL-1beta expression. Inhibitors, antagonists and the small interfering RNA technique were used to investigate the involvement of Panx1 in IL-1beta induction. Co immunoprecipitation (Co-IP) and immunostaining were used to determine the association of Panx1 with the P2X7 receptor. The IL-1beta release mechanism was analyzed using inhibitors. RESULTS: Blocking Panx1 significantly decreased ATP release, as well as IL-1beta up-regulation, upon stimulation with stress or ATP. Co-IP revealed the association of Panx1 and the P2X7 receptor in HPDL cells, which was increased in response to mechanical loading. Pretreatment with vesicular trafficking inhibitors significantly reduced the amount of IL-1beta released from stimulated cells, suggesting that IL-1beta might be released through vesicles. CONCLUSION: We clearly illustrated the contribution of Panx1 in ATP release, as well as in IL-1beta induction in HPDL cells. The association of Panx1 and the P2X7 receptor might be required for IL-1beta induction, and their possible novel role in IL-1beta vesicular release was indicated. PMID- 24219424 TI - Diagnostic lumbar puncture in suspected acute bacterial meningitis: avoiding catastrophe. PMID- 24219422 TI - Budesonide and formoterol effects on rhinovirus replication and epithelial cell cytokine responses. AB - BACKGROUND: Combination therapy with budesonide and formoterol reduces exacerbations of asthma, which are closely associated with human rhinovirus (RV) infections in both children and adults. These data suggest that budesonide and formoterol inhibit virus-induced inflammatory responses of airway epithelial cells. METHODS: To test this hypothesis, bronchial epithelial (BE) cells were obtained from airway brushings of 8 subjects with moderate-to-severe allergic asthma and 9 with neither asthma nor respiratory allergies. Cultured BE cells were incubated for 24 hours with budesonide (1.77 uM), formoterol (0.1 uM), both, or neither, and then inoculated with RV-16 (5*10(6) plaque forming units [PFU]/mL). After 24 hours, viral replication (RV RNA), cytokine secretion (CXCL8, CXCL10, TNFa, IFN-beta, IL-28) and mRNA expression (CXCL8, CXCL10, TNF, IFNB1, IL 28) were analyzed. RESULTS: RV infection induced CXCL10 protein secretion and IFNB1 and IL28 mRNA expression. Drug treatments significantly inhibited secretion of CXCL10 in mock-infected, but not RV-infected, BE cells, and inhibited secretion of TNFa under both conditions. Neither budesonide nor formoterol, alone or in combination, significantly affected viral replication, nor did they inhibit RV-induced upregulation of IFNB1 and IL28 mRNA. Overall, RV replication was positively related to CXCL10 secretion and induction of IFNB1 and IL28 mRNA, but the positive relationship between RV RNA and CXCL10 secretion was stronger in normal subjects than in subjects with asthma. CONCLUSIONS: Budesonide and formoterol can inhibit BE cell inflammatory responses in vitro without interfering with viral replication or production of interferons. These effects could potentially contribute to beneficial effects of budesonide/formoterol combination therapy in preventing RV-induced asthma exacerbations. PMID- 24219425 TI - Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks. AB - RATIONALE, AIMS, AND OBJECTIVES: Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. METHODS: A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. RESULTS: Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross network coordinating centre, and creating common budget and payment mechanisms. CONCLUSIONS: The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. PMID- 24219427 TI - Alien insects in Italy: comparing patterns from the regional to European level. AB - The introduction of species outside their native range contributes to the loss of biodiversity, alters the structure and functioning of ecosystems, and damages economy and human health. Insects are one of the taxa with the highest frequency of introduction due to their high diversity, biological properties, and close association with human activities. Here, the allodiversity of Italian entomofauna was analyzed, with a focus on Tuscany (Central Italy). A list of alien insects in Tuscany is included. The status of the alien entomofauna in Italy was updated. The number of alien insects amounts to 122 in Tuscany and 923 in Italy. An introduction rate of 98 species per decade was estimated in Italy. In Tuscany, alien insects belong to 10 orders, mostly Coleoptera (38%), Hemiptera (Sternorrhyncha and Auchenorrhyncha) (23%), and Hymenoptera (13%). They have been most often introduced through vegetable items (ornamental plants or crops). Most species come from the Nearctic region (26%) and are both phytophagous (63%) and amphigonic (80%). Differences and similarities in introduction patterns and in insect abundances across orders among regional, national, and European scales, also considering worldwide abundances, are discussed. Finally, a paucity of information regarding the negative impacts of many species, except for economic pests, phytosanitary threats, and vectors of disease, is underlined. A deeper understanding of the alien insects' ecological impact might help designate policies aimed at preventing further introductions and control the invasive populations of already established species. PMID- 24219426 TI - Photochemical oxidation of a manganese(III) complex with oxygen and toluene derivatives to form a manganese(V)-oxo complex. AB - Visible light photoirradiation of an oxygen-saturated benzonitrile solution of a manganese(III) corrolazine complex [(TBP8Cz)Mn(III)] (1): [TBP8Cz = octakis(p tert-butylphenyl)corrolazinato(3-)] in the presence of toluene derivatives resulted in formation of the manganese(V)-oxo complex [(TBP8Cz)Mn(V)(O)]. The photochemical oxidation of (TBP8Cz)Mn(III) with O2 and hexamethylbenzene (HMB) led to the isosbestic conversion of 1 to (TBP8Cz)Mn(V)(O), accompanied by the selective oxidation of HMB to pentamethylbenzyl alcohol (87%). The formation rate of (TBP8Cz)Mn(V)(O) increased with methyl group substitution, from toluene, p xylene, mesitylene, durene, pentamethylbenzene, up to hexamethylbenzene. Deuterium kinetic isotope effects (KIEs) were observed for toluene (KIE = 5.4) and mesitylene (KIE = 5.3). Femtosecond laser flash photolysis of (TBP8Cz)Mn(III) revealed the formation of a tripquintet excited state, which was rapidly converted to a tripseptet excited state. The tripseptet excited state was shown to be the key, activated state that reacts with O2 via a diffusion-limited rate constant. The data allow for a mechanism to be proposed in which the tripseptet excited state reacts with O2 to give the putative (TBP8Cz)Mn(IV)(O2(*-)), which then abstracts a hydrogen atom from the toluene derivatives in the rate determining step. The mechanism of hydrogen abstraction is discussed by comparison of the reactivity with the hydrogen abstraction from the same toluene derivatives by cumylperoxyl radical. Taken together, the data suggest a new catalytic method is accessible for the selective oxidation of C-H bonds with O2 and light, and the first evidence for catalytic oxidation of C-H bonds was obtained with 10-methyl-9,10-dihydroacridine as a substrate. PMID- 24219428 TI - Safety of anti-tumor necrosis factor agents in psoriatic arthritis - an update. AB - INTRODUCTION: Tumor necrosis factor (TNF) blockers have represented a real revolution in the treatment of rheumatoid arthritis and spondyloarthritides (SpAs). In the case of psoriatic arthritis (PsA), anti-TNF agents are much more effective than conventional disease modifying antirheumatic drugs on all manifestations of the disease, that is, axial involvement, peripheral arthritis, peripheral enthesitis, dactylitis and skin lesions. A complete understanding of their safety is fundamental in clinical practice. AREAS COVERED: This article addresses the safety of anti-TNF therapy in PsA. A systematic literature review was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE). The reported data were derived from randomized controlled trials, open observational studies and meta-analyses. Useful information derived from the experiences in rheumatoid arthritis has also been reported. EXPERT OPINION: Anti TNF therapies are as safe as conventional disease-modifying antirheumatic drugs in the management of psoriatic arthritis when the candidate patients are accurately selected. An adverse event could still occur when the patient is managed according to current national and/or international recommendations; therefore, tight controls aimed to detect adverse events early is mandatory. PMID- 24219429 TI - Development of a broad-host synthetic biology toolbox for Ralstonia eutropha and its application to engineering hydrocarbon biofuel production. AB - BACKGROUND: The chemoautotrophic bacterium Ralstonia eutropha can utilize H2/CO2 for growth under aerobic conditions. While this microbial host has great potential to be engineered to produce desired compounds (beyond polyhydroxybutyrate) directly from CO2, little work has been done to develop genetic part libraries to enable such endeavors. RESULTS: We report the development of a toolbox for the metabolic engineering of Ralstonia eutropha H16. We have constructed a set of broad-host-range plasmids bearing a variety of origins of replication, promoters, 5' mRNA stem-loop structures, and ribosomal binding sites. Specifically, we analyzed the origins of replication pCM62 (IncP), pBBR1, pKT (IncQ), and their variants. We tested the promoters P(BAD), T7, P(xyls/PM), P(lacUV5), and variants thereof for inducible expression. We also evaluated a T7 mRNA stem-loop structure sequence and compared a set of ribosomal binding site (RBS) sequences derived from Escherichia coli, R. eutropha, and a computational RBS design tool. Finally, we employed the toolbox to optimize hydrocarbon production in R. eutropha and demonstrated a 6-fold titer improvement using the appropriate combination of parts. CONCLUSION: We constructed and evaluated a versatile synthetic biology toolbox for Ralstonia eutropha metabolic engineering that could apply to other microbial hosts as well. PMID- 24219430 TI - HPTLC determination of chemical composition variability in raw materials used in botanicals. AB - Besides the chemotaxonomic value, nowadays determination of biodiversity and chemical variability has a commercial impact. The exact identity of raw material and constituents of botanical products, such as food supplements or herbal remedies, is a very important argument, being the real prerequisite for quality control and traceability, followed by the determination of active components. However, the analytical approach must consider the natural great variability in secondary metabolites and product form, such as in extracts. Against the reductive approach, on the basis of single chemical standards, so far dominant in Pharmacopoeias monographs, we report applications and utility of the high performance thin-layer chromatography fingerprint in determination of species of the same genus, of populations of the same species and of different drugs of the same plant. PMID- 24219431 TI - Lipid resuscitation in pediatric patients - need for caution? AB - A 3-year-old child was successfully resuscitated following bupivacaine cardiotoxicity with 20% intravenous lipid emulsion (ILE). Large volume of ILE was used targeting clinically adequate perfusion. Subsequently, there were features of ventilation/perfusion (V/P) mismatch. PMID- 24219432 TI - Pay-freeze proposal will cost government dear. PMID- 24219433 TI - Nurses make ends meet through extra shifts and payday loans. PMID- 24219434 TI - Carter criticises 'divisive' flu jab funding restriction. PMID- 24219438 TI - Unfilled and deleted posts combine to create staffing crisis, says college. PMID- 24219439 TI - NICE to develop long-awaited guidance on safe staffing levels. PMID- 24219447 TI - NMC in bid to overturn 'lenient' ruling against ex-Mid Staffs nurse. PMID- 24219449 TI - Living hand to mouth - how nurses deal with the reality of pay restraint. PMID- 24219455 TI - Kidney cancer. PMID- 24219456 TI - Centre of excellence. AB - In August, the refurbished RCN Library and Heritage Centre opened at the college's London headquarters. As well as a comprehensive collection of nursing literature, it offers a relaxing 'club' environment where nurses can meet , study socialise . Exhibitions, drawing on the college's unrivalled archive of nursing materials, showcase nursing's achievements and stimulate discussion. PMID- 24219457 TI - The high achiever. AB - Julie Lamb, joint winner of the Nursing Standard nurse of the year award in 1996, lobbied her local health authority to establish a cancer unit at the Essex hospital where she worked. This saved sick patients from having to travel to London for chemotherapy. Her career flourished after winning and she moved into management. PMID- 24219458 TI - Paper-free future. AB - Nurses are increasingly recording patient information electronically. But getting this right requires the right IT support. Staff at one trust describe how they are moving towards electronic nursing risk assessments, while a nurse at another discusses the advantages of doing so. PMID- 24219459 TI - Meditate to medicate. AB - Emeritus professor of medicine John Kabat-Zinn was invited to advise Downing Street earlier this year. He is the founding director of the Stress Reduction Clinic and the center for mindfulness in medicine, health care and society at the University of Massachusetts Medical School. PMID- 24219482 TI - Genetics: advocating for the rights of all individuals to informed decision making and voluntary action. AB - This is the fourth article in a series describing how nurses can develop their confidence and competence in genetics and genomics health care. The focus of this article is the right of the individual to make an informed choice, to be supported to make that choice and to do so in a voluntary manner. Nurses are well placed to support patients who may be considering genetic testing and are often responsible for gaining their consent for such investigations. It is essential that they provide balanced information in a way that the patient can understand and are able to explain the different options and possible outcomes of genetic tests, while considering the wider implications this may have on the patient's family. PMID- 24219483 TI - Risk of suicide in patients with dementia: a case study. AB - Evidence indicates that the risk of attempted suicide is a significant issue among people with dementia, however there is a lack of information to guide professional practice. This article uses a case study to reflect on the risk management strategies and ethics of suicide and assisted suicide in relation to a specific patient with dementia. It analyses recommendations aimed at improving the lived experience of people with dementia and those involved in their care, including providing patients with a formal diagnosis as early as possible. PMID- 24219484 TI - Whooping cough: identification, assessment and management. AB - Although there is a high uptake of vaccinations providing protection against Bordetella pertussis, the main cause of whooping cough, there has been an increase in the incidence of notifications of the disease in the UK and other developed countries in recent years. The increase in cases of whooping cough is mainly evident in older children and adults. While these individuals may experience persistent and unpleasant symptoms, most notably prolonged cough, symptoms may be mild, in part, because most older children and adults have been vaccinated against the disease. The most significant public health concern relating to whooping cough is that infected older children and adults may transmit the disease to unvaccinated infants who are most vulnerable to the symptoms. This article aims to develop the reader's understanding of whooping cough, including its prevention and management. PMID- 24219485 TI - Constructive feedback. AB - The CPD article on providing constructive feedback to nursing students was particularly relevant since I recently completed a student mentoring course and am now mentoring a nursing student. PMID- 24219486 TI - The valued workforce. AB - Students on the pre-registration nursing course at Edinburgh Napier University are taught with a particular emphasis on compassion in care. Compassion is woven through the course, starting with the way students are recruited based on these values. PMID- 24219487 TI - Signposts to job satisfaction. AB - A report by recruitment and human resources services provider Randstad Care claimed recently that 40 per cent of UK nurses it surveyed were happy with their career progression. PMID- 24219489 TI - Abuse is a healthcare issue. AB - With one in four women in the UK affected by domestic abuse, and those who experience it more likely to use health services, nurses can play a pivotal role in tackling its impact. Yet nurses often lack knowledge about how to help. PMID- 24219490 TI - Student life - From Africa to the Americas. AB - The most memorable year of my nurse training at King's College London was in 2011, when I took a four-week nursing elective in Tanzania followed by a nursing exchange between King's and the University of Pennsylvania (UPenn). PMID- 24219491 TI - Onset of bonding plasmon hybridization preceded by gap modes in dielectric splitting of metal disks. AB - Dielectric splitting of nanoscale disks was studied experimentally and via finite difference time-domain (FDTD) simulations through systematic introduction of multiple ultrathin dielectric layers. Tunable, hybridized dark bonding modes were seen with first-order gap modes preceding the appearance of bonding dipole-dipole disk modes. The observed bright dipolar mode did not show the energy shift expected from plasmon hybridization but activated dark higher order gap modes. Introducing lateral asymmetry was shown to remodel the field distribution resulting in 3D asymmetry that reoriented the dipole orientation away from the dipole of the elementary disk modes. PMID- 24219492 TI - Type A personality, hostility, time urgency and unintentional injuries among Chinese undergraduates: a matched case-control study. AB - BACKGROUND: Associations between type A behaviour pattern (TABP) and injuries are inconsistent. These inconsistencies may be due to different effects of various components of TABP, namely time urgency/impatience, hostility and competitive drive. It is important to examine the relationship between the global TABP, its two components, and unintentional injuries, among undergraduates in China. METHODS: On the basis of a previous cross-sectional study, we conducted a matched case-control study. 253 cases and an equal number of age-, gender-, and major matched controls were included. The questionnaire solicited socio-demographic information, the experience of injuries, the scale of TABP, and other potential confounding factors. Besides the correlation between the global TABP and injuries, the influences of the two components of TABP on injuries were also evaluated. Conditional logistic regression was used to determine the crude odds ratios (ORs) and adjusted ORs of injury events. RESULTS: A dose-response relationship was apparent among students who rated themselves higher on the TABP scale (P-value for trend, 0.002), with a crude OR of 2.93 (95% CI: 0.93-9.19) for injuries comparing those with TABP to those with type B behaviour pattern (TBBP). After adjustment for potential confounding factors, TABP remained statistically significant, and the adjusted OR was 5.52 (95% CI: 1.43-21.27); from a comparison of students with TABP to those with TBBP. A dose-response relationship was also apparent between the hostility component and nonfatal injuries, both in crude analysis and after adjusting for other confounders. The relationship between time hurry and injuries was not statistically significant, based on univariate and multivariate analyses. CONCLUSIONS: Both the global TABP and the hostility component were associated with a dose response increase in the risk of non-fatal unintentional injuries among Chinese undergraduates. Further studies need to be conducted to confirm or reject this correlation. PMID- 24219493 TI - Botulinum toxin field assays evaluated using cosmetic botox preparations. AB - Several quick tests for identifying botulinum toxins (BoNTs) are commercially available, but generally these tests have not been evaluated by independent laboratories. This study presents data on the evaluation of a number of commercial tests and demonstrates the use of cosmetic preparations of BoNT A and B as positive controls. For reference we used an in-house ELISA procedure. The cosmetic toxins, Botox((r)) and Neurobloc((r)), were found to be useful-that is, they had a sufficiently high toxin content to be used in test evaluation studies. Some commercial kits based on columns (ABICAP((r))) or lateral flow technology were tested for their detection limits. The ABICAP column system was found to be a useful alternative to an in-house ELISA method. In general, the lateral flow based test systems evaluated here were not able to detect BoNT, and a large proportion of the tests showed construction failures. In conclusion, this study showed that cosmetic BoNT products have enough toxin content to be used as convenient and accessible means of testing commercially available quick tests. The lateral flow tests used in this study were not satisfactory, while the ABICAP system was found to be a good alternative to an ELISA. PMID- 24219494 TI - Public health emergencies and responses: what are they, how long do they last, and how many staff does your agency need? AB - Responding to outbreaks is one of the most routine yet most important functions of a public health agency. However, some outbreaks are bigger, more visible, or more complex than others, prompting discussion about when an "outbreak" becomes a "public health emergency." When a public health emergency is identified, resources (eg, funding, staff, space) may need to be redirected from core public health programs to contribute to the public health emergency response. The need to sustain critical public health functions while preparing for public health emergency responses raises a series of operational and resource management questions, including when a public health emergency begins and ends, why additional resources are needed, how long an organization should expect staff to be redirected, and how many staff (or what proportion of the agency's staff ) an organization should anticipate will be needed to conduct a public health emergency response. This article addresses these questions from a national perspective by reviewing events for which the Centers for Disease Control and Prevention redirected staff from core public health functions to respond to a series of public health emergencies. We defined "public health emergency" in both operational and public health terms and found that on average each emergency response lasted approximately 4 months and used approximately 9.5% of our workforce. We also provide reasons why public health agencies should consider the impact of redirecting resources when preparing for public health emergencies. PMID- 24219495 TI - Beyond sports nutrition: the diverse role of dietitians at the Delhi 2010 Commonwealth Games. AB - BACKGROUND: Although registered sports dietitians commonly assist athletes with training and competition nutrition advice, an emerging area of practice is focused around food provision and nutrition support provided at major competition events. The present study aimed, first, to identify the dietetic skills and scope of practice that dietitians may require to work in this environment as determined by the occasions of service provided by dietitians at a nutrition kiosk located in the dining hall at a major competition event and, second, to investigate athletes' opinion and usage of the nutrition services and the association with their type of sport and previous source of nutrition information. METHODS: Dietitians based at a nutrition kiosk recorded all enquiries (n = 383) and consultations (n = 60) from 23 September to 14 October 2010. A questionnaire was also distributed to athletes in the main dining hall over this period to investigate their opinion and use of nutrition support, as well as their previous source of nutrition information. RESULTS: Although athletes from Western regions made up the majority of the enquiries regarding food provision and special/therapeutic dietary requirements (predominately food allergy and intolerance), athletes from non-Western regions, and those in weight category sports, had more sports nutrition enquiries and were more likely to request a consultation. A number of athletes (32%) reported no previous or one source of nutrition information, whereas only eight of 52 athletes who requested a consultation had prior nutrition assistance. CONCLUSIONS: In addition to sport nutrition knowledge and experience, dietitians working in this environment are likely to require an understanding of cultural eating styles, food beliefs and customs, large-scale food service operation, and local food availability. PMID- 24219496 TI - RNA polymerase structure, function, regulation, dynamics, fidelity, and roles in gene expression. PMID- 24219497 TI - Plasma Rich in Growth Factors Improves Patients' Postoperative Quality of Life in Maxillary Sinus Floor Augmentation: Preliminary Results of a Randomized Clinical Study. AB - PURPOSE: The control of postoperative discomfort may improve the patient's quality of life as well as treatment acceptance. The aim of the present preliminary report was to assess if the use of autologous platelet concentrate during maxillary sinus augmentation may have a favorable impact on pain and other factors related to patient's quality of life in the first week after surgery. MATERIALS AND METHODS: This is an interim report of a randomized single-blind study. Fifteen patients with atrophic edentulous posterior maxilla underwent maxillary sinus augmentation using deproteinized bovine bone matrix (DBBM) as the grafting material (control group). In other 15 patients (test group), autologous plasma rich in growth factors (P-PRP) was added to DBBM, then a P-PRP clot was applied to covering the graft before suturing and finally P-PRP was placed over the suture in liquid form. During the first week postsurgery, all patients filled in a questionnaire for evaluation of main symptoms and daily activities. The outcomes of the questionnaires of the two groups were statistically compared. RESULTS: In the first days postsurgery, the group using P-PRP reported significantly less pain, swelling, and hematoma, and improved functional activities with respect to the control group. CONCLUSIONS: The adjunct of P-PRP to the maxillary sinus augmentation procedure produced a beneficial effect to patients' quality of life in the early postsurgical phase. PMID- 24219498 TI - Incretin-mimetics associated pancreatitis: evidence from the spontaneous adverse drug reactions reporting in Italy. AB - OBJECTIVE: New incretin-mimetics increased the treatment options for type 2 diabetes mellitus. Studies on the safety of incretin-based therapy showed a risk of hypersensitivity reactions, acute pancreatitis, renal failure, infection, thyroid and pancreas cancer. We contributed to safety assessment of these new drugs by evaluating the spontaneous adverse drug reactions (ADRs) reporting in Italy. RESEARCH AND METHODS: Reports of suspected ADRs associated with incretin mimetics were selected from the Italian Spontaneous ADR Reporting Database. For a subgroup of cases belonging to the Hospital of Cento (Ferrara), levels of pancreatic enzymes, amylase and lipase, before and after the therapy with the incretin-mimetics were available. RESULTS: As of December 2012, the reports of ADR associated with hypoglycemic drugs (excluding insulin) were 2443, 1169 (47.85%) concerned the incretin-mimetics. A total of 90 reports described pancreatitis (44) and elevated pancreatic enzymes (46). Out of 90 cases, 34 were serious (37%). Data on amylase/lipase values for 10 patients were provided and an analysis of the published literature was performed. CONCLUSIONS: Our data from the daily clinical practice add up and confirm the information available on the association between incretin-mimetics and pancreatic damage and suggest caution in the prescribing of these new drugs and a close monitoring of exposed patients. PMID- 24219499 TI - Crystal structures and photoluminescence across the La2Si2O7-Ho2Si2O7 system. AB - It is well-known that when an RE2Si2O7 matrix is doped with active lanthanide ions, it displays promising luminescent responses for optical applications. The crystalline structure adopted by the silicate matrix as well as the distribution of the dopants among the available RE crystallographic sites have important effects on the luminescent yields of these compounds. The present study is aimed at analyzing the structural behavior as well as the luminescent properties of Ho(3+)-substituted La2Si2O7. Several compositions across the La2Si2O7-Ho2Si2O7 system were synthesized using the sol-gel method followed by calcination at 1600 degrees C. The resulting powders were analyzed by means of X-ray and neutron diffraction to determine the phase stabilities across the system. The results indicated a solid solubility region of G-(La,Ho)2Si2O7 which extends to the La0.6Ho1.4Si2O7 composition. Compositions richer in Ho(3+) show a two-phase domain (G+delta), while delta-(La,Ho)2Si2O7 is the stable phase for Ho(3+) contents higher than 90% (La0.2Ho1.8Si2O7). Anomalous diffraction data interestingly indicated that the La(3+) for Ho(3+) substitution mechanism in the G-(La,Ho)2Si2O7 polymorph is not homogeneous, but a preferential occupation of Ho(3+) for the RE2 site is observed. The Ho(3+)-doped G-La2Si2O7 phosphors exhibited a strong green luminescence after excitation at 446 nm. Lifetime measurements indicated that the optimum phosphor was that with a Ho(3+) content of 10%. PMID- 24219500 TI - B cell-mediated antigen transport to splenic follicles. PMID- 24219501 TI - The association between children's contact with people with disabilities and their attitudes towards disability: a systematic review. AB - AIM: The aim of this review was to systematically review and synthesize observational evidence of associations between children's naturally varying contact with people with disabilities and their attitudes towards disability. METHOD: A comprehensive search was conducted across multiple databases. Studies were included if they measured children's contact with people with disabilities and their attitudes towards disability. Qualitative research and studies that experimentally varied the amount of contact children had were excluded. Data were synthesized in a narrative review. RESULTS: There were 35 studies that met the inclusion criteria: 22 of these reported a statistically significant association between contact with people with disabilities and more positive attitudes towards disability; two studies reported a negative association between contact and attitudes; and 11 studies reported no association. Incomplete reporting of the methods and results across studies limited the conclusions that could be drawn. INTERPRETATION: Studies identified in this review generally indicate that children's contact with people with disabilities is associated with more positive attitudes towards disability. There is a need for more rigorous research to examine the effect of children's contact with people with disabilities on their attitudes towards disability. PMID- 24219502 TI - Inter- and intraspecific identification of the screwworm, Cochliomyia hominivorax, using random amplified polymorphic DNA-polymerase chain reaction. AB - The screwworm, Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), is one of the most devastating arthropod pests of livestock in the Western Hemisphere. Early instars are very difficult to distinguish morphologically from several closely related blow fly species. Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) markers were developed for identifying C. hominivorax from other wound inhabiting species. Forty decameric primers were screened; nine showed clear reproducible RAPD profiles suitable for distinguishing all life stages of C. hominivorax from 7 other species, including C. macellaria (Fabricius). The results from RAPD-PCR with field-collected samples of unknown first instars agreed with morphological identification that the samples were not C. hominivorax. Three different primers showed DNA polymorphisms (intraspecific) for samples originating from Mexico, Costa Rica, Panama, Jamaica, and Brazil. Therefore, RAPD-PCR may be useful for determining the geographic origin of C. hominivorax samples. Comparing products from these primers, used with known and unknown screwworm samples from an outbreak in Mexico, clearly showed that the outbreak did not originate from the mass rearing facility. Accurate identification of suspected C. hominivorax samples is possible using RAPD-PCR. Further development to identify the geographic origin of samples would benefit the ongoing surveillance programs against C. hominivorax and the decision process during suspected outbreaks of this important pest. PMID- 24219503 TI - Influence of gold nanoparticles on the kinetics of alpha-synuclein aggregation. AB - alpha-synuclein (AS) is a small (140 amino acids), abundant presynaptic protein, which lacks a unique secondary structure in aqueous solution. Amyloid aggregates of AS in dopaminergic neurons of the midbrain are the hallmark of Parkinson's disease (PD). The process of aggregation involves a series of complex structural transitions from innocuous monomeric AS to oligomeric, presumably neurotoxic, forms and finally to fibril formation. Despite its potential importance for understanding PD pathobiology and devising rational, targeted therapeutic strategies, the details of the aggregation process remain largely unknown. Methodologies and reagents capable of controlling the aggregation kinetics are essential tools for the investigation of the molecular mechanisms of amyloid diseases. In this work, we investigated the influence of citrate-capped gold nanoparticles on the aggregation kinetics of AS using a fluorescent probe (MFC) sensitive to the polarity of the molecular microenvironment via excited state intramolecular proton transfer (ESIPT). The particular effects on the half time, nucleation time, and growth rate were ascertained. Gold nanoparticles produced a strong acceleration of protein aggregation with an influence on both the nucleation and growth phases of the overall mechanism. The effects were dependent on the size and concentration of the nanoparticles, being strongest for nanoparticles 10 nm in diameter, which produced a 3-fold increase in the overall aggregation rate at concentrations as low as 20 nM. PMID- 24219504 TI - National health insurance scheme enrolment and antenatal care among women in Ghana: is there any relationship? AB - OBJECTIVES: The objective of this study was to examine whether enrolment in the National Health Insurance Scheme (NHIS) affects the likelihood and timing of utilising antenatal care among women in Ghana. METHODS: Data were drawn from the Ghana Demographic and Health Survey, a nationally representative survey collected in 2008. The study used a cross-sectional design to examine the independent effects of NHIS enrolment on two dependent variables (frequency and timing of antenatal visits) among 1610 Ghanaian women. Negative binomial and logit models were fitted given that count and categorical variables were employed as outcome measures, respectively. RESULTS: Regardless of socio-economic and demographic factors, women enrolled in the NHIS make more antenatal visits compared with those not enrolled; however, there was no statistical association with the timing of the crucial first visit. Women who are educated, living in urban areas and are wealthy were more likely to attend antenatal care than those living in rural areas, uneducated and from poorer households. CONCLUSION: The NHIS should be strengthened and resourced as it may act as an important tool for increasing antenatal care attendance among women in Ghana. PMID- 24219505 TI - PlantTFcat: an online plant transcription factor and transcriptional regulator categorization and analysis tool. AB - BACKGROUND: Plants regulate intrinsic gene expression through transcription factors (TFs), transcriptional regulators (TRs), chromatin regulators (CRs), and the basal transcription machinery. An understanding of plant gene regulatory mechanisms at a systems level requires the identification of these regulatory elements on a genomic scale. RESULTS: Here, we present PlantTFcat, a high performance web-based analysis tool that is designed to identify and categorize plant TF/TR/CR genes from genome-scale protein and nucleic acid sequences by systematically analyzing InterProScan domain patterns in protein sequences. The comprehensive prediction logics that are included in PlantTFcat are based on relationships between gene families and conserved domains from 108 published plant TF/TR/CR families. These prediction logics effectively distinguish TF/TR/CR families with common conserved domains. Our systematic performance evaluations indicate that PlantTFcat annotates known TF/TR/CR families with high coverage and sensitivity. CONCLUSIONS: PlantTFcat provides an analysis tool to identify and categorize plant TF/TR/CR genes on a genomic scale. PlantTFcat is freely available to the public at http://plantgrn.noble.org/PlantTFcat/. PMID- 24219507 TI - Climate change effects on Chikungunya transmission in Europe: geospatial analysis of vector's climatic suitability and virus' temperature requirements. AB - BACKGROUND: Chikungunya was, from the European perspective, considered to be a travel-related tropical mosquito-borne disease prior to the first European outbreak in Northern Italy in 2007. This was followed by cases of autochthonous transmission reported in South-eastern France in 2010. Both events occurred after the introduction, establishment and expansion of the Chikungunya-competent and highly invasive disease vector Aedes albopictus (Asian tiger mosquito) in Europe. In order to assess whether these outbreaks are indicative of the beginning of a trend or one-off events, there is a need to further examine the factors driving the potential transmission of Chikungunya in Europe. The climatic suitability, both now and in the future, is an essential starting point for such an analysis. METHODS: The climatic suitability for Chikungunya outbreaks was determined by using bioclimatic factors that influence, both vector and, pathogen. Climatic suitability for the European distribution of the vector Aedes albopictus was based upon previous correlative environmental niche models. Climatic risk classes were derived by combining climatic suitability for the vector with known temperature requirements for pathogen transmission, obtained from outbreak regions. In addition, the longest potential intra-annual season for Chikungunya transmission was estimated for regions with expected vector occurrences.In order to analyse spatio-temporal trends for risk exposure and season of transmission in Europe, climate change impacts are projected for three time-frames (2011-2040, 2041-2070 and 2071-2100) and two climate scenarios (A1B and B1) from the Intergovernmental Panel on Climate Change (IPCC). These climatic projections are based on regional climate model COSMO-CLM, which builds on the global model ECHAM5. RESULTS: European areas with current and future climatic suitability of Chikungunya transmission are identified. An increase in risk is projected for Western Europe (e.g. France and Benelux-States) in the first half of the 21st century and from mid-century onwards for central parts of Europe (e.g. Germany). Interestingly, the southernmost parts of Europe do not generally provide suitable conditions in these projections. Nevertheless, many Mediterranean regions will persist to be climatically suitable for transmission. Overall, the highest risk of transmission by the end of the 21st century was projected for France, Northern Italy and the Pannonian Basin (East-Central Europe). This general tendency is depicted in both, the A1B and B1 climate change scenarios. CONCLUSION: In order to guide preparedness for further outbreaks, it is crucial to anticipate risk as to identify areas where specific public health measures, such as surveillance and vector control, can be implemented. However, public health practitioners need to be aware that climate is only one factor driving the transmission of vector-borne disease. PMID- 24219508 TI - Efficacy and safety of mirodenafil for patients with erectile dysfunction: a meta analysis of three multicenter, randomized, double-blind, placebo-controlled clinical trials. AB - AIM: To systematically review evidence on the efficacy and safety of mirodenafil treatment in erectile dysfunction (ED) from randomised controlled trials. METHODS: We searched PubMed, Embase and the Cochrane Library database up to March 2013. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary). RESULTS: A total of 374 participants from three randomized controlled trials were identified in this meta-analysis. After 12 weeks treatment, mirodenafil was found to be more effective than placebo, and tolerability was good. The pooled results showed that the IIEF EFD score for 100 mg mirodenafil group was higher than placebo group (MD = 8.13, 95%CI: 6.64-9.61, p < 0.00001) and the mirodenafil group was also higher than placebo group in the changes from baseline for the IIEF EFD score (MD = 7.32, 95%CI: 5.56-9.07, p < 0.00001), respectively. The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15.8% versus 3.2%, 3.1% versus 0%; respectively). CONCLUSION: This meta analysis suggested that mirodenafil is effective and well-tolerated therapy for ED. PMID- 24219509 TI - Molecular simulation of water extraction into a tri-n-butylphosphate/n-dodecane solution. AB - Molecular dynamics simulations were performed to investigate water extraction into a solution of 30 vol % tri-n-butylphosphate (TBP) in n-dodecane. Our computational results indicate that the TBP electric dipole moment has a significant effect on the predicted water solubility. A larger TBP dipole moment decreases the aqueous-organic interfacial tension, leading to increased roughness of the aqueous-organic interface. Interfacial roughness disrupts the interfacial water hydrogen bonding structure, resulting in a presence of dangling water molecules at the interface. The increased interfacial roughness enhances the probability of water molecules breaking away from the aqueous phase and migrating into the organic bulk phase. By varying the atomic partial charges of the TBP molecules to reproduce a dipole moment close to the experimentally measured value, we were able to predict water solubility in close agreement with experimental measurements. In addition, our simulation results reveal the detailed molecular mechanism of the water extraction process, and the various structural forms of water molecules both at the interface and in the bulk organic phase. PMID- 24219510 TI - Trajectories of self-efficacy in persons with chronic illness: an explorative longitudinal study. AB - BACKGROUND: Self-efficacy is important for changing health behaviour in persons with chronic illness. Longer term trajectories have not been previously explored. OBJECTIVE: This study's objective was to explore the trajectories of self efficacy in two different groups with chronic illnesses attending a patient education course. DESIGN: The study design was a longitudinal, comparative cohort study with five time points during a one-year follow-up, using repeated measures analysis of variance. SETTING AND PARTICIPANTS: Persons with morbid obesity (n = 55) and persons with chronic obstructive pulmonary disease (COPD; n = 56) were recruited at the start of patient education courses in Norway and followed-up four times the following year. MAIN OUTCOME MEASURE: The General Self-Efficacy Scale was the main outcome. RESULTS: Obese persons showed a linear pattern of increasing self-efficacy during the follow-up period, whereas persons with COPD had an initial increase followed by a decrease in self-efficacy. Having paid work was associated with a more positive self-efficacy trajectory. CONCLUSION: The results provide support for the currently employed patient education course for morbidly obese persons. In contrast, persons with COPD may need more extensive and/or more frequent support in order to increase and maintain self-efficacy across time. PMID- 24219512 TI - Implicit memory formation using the word stem completion task during anesthesia in children. AB - AIMS: To determine whether there is evidence of implicit memory formation during pediatric anesthesia using the word stem completion task. BACKGROUND: In adults, there is mixed evidence for implicit memory formation during anesthesia; however, there is no evidence in children. Implicit memory in adults has been detected using the word stem completion task. This test has not been used in a pediatric anesthetic setting. METHODS: A total of 200 patients aged 7-12 were randomized to hear one of the two lists of 10 words played continuously while anesthetized. Group 1 heard List A and Group 2 heard List B. Postoperatively, 194 completed a word stem completion task where they were required to complete the stems (the first part of words) corresponding to the words on the two word lists combined, with the first word that came to mind. RESULTS: Group 1 completed a mean of 2.78 words correctly from List A and a mean of 2.70 words correctly from List B. Group 2 completed a mean of 3.29 words correctly from List A and a mean of 3.66 words correctly from List B. For List A, there was no evidence (P = 0.70) for an association between intraoperative exposure to this list and the odds of successfully completing a stem from this list with the corresponding target word. There was little evidence (P = 0.09) for an association with List B. CONCLUSION: This study found no strong evidence that children form implicit memories for auditory words during anesthesia. Given the difference between lists, future research is warranted using carefully chosen word stems. PMID- 24219514 TI - Multiple excitation of confined graphene plasmons by single free electrons. AB - We show that free electrons can efficiently excite plasmons in doped graphene with probabilities in the order of one per electron. More precisely, we predict multiple excitations of a single confined plasmon mode in graphene nanostructures. These unprecedentedly large electron-plasmon couplings are explained using a simple scaling law and further investigated through a general quantum description of the electron-plasmon interaction. From a fundamental viewpoint, multiple plasmon excitations by a single electron provide a unique platform for exploring the bosonic quantum nature of these collective modes. Not only does our study open a viable path toward multiple excitation of a single plasmon mode by a single electron, but it also reveals electron probes as ideal tools for producing, detecting, and manipulating plasmons in graphene nanostructures. PMID- 24219511 TI - Targeting insulin-like growth factor-I and insulin-like growth factor-binding protein-3 signaling pathways. A novel therapeutic approach for asthma. AB - Insulin-like growth factor (IGF)-I has been recognized to play critical roles in the pathogenesis of asthma, whereas IGF-binding protein (IGFBP)-3 blocks crucial physiologic manifestations of asthma. IGF-I enhances subepithelial fibrosis, airway inflammation, airway hyperresponsiveness, and airway smooth muscle hyperplasia by interacting with various inflammatory mediators and complex signaling pathways, such as intercellular adhesion molecule-1, and the hypoxia inducible factor/vascular endothelial growth factor axis. On the other hand, IGFBP-3 decreases airway inflammation and airway hyperresponsiveness through IGFBP-3 receptor-mediated activation of caspases, which subsequently inhibits NF kappaB signaling pathway. It also inhibits the IGF-I/hypoxia-inducible factor/vascular endothelial growth factor axis via IGF-I-dependent and/or IGF-I independent mechanisms. This Translational Review summarizes the role of IGF-I and IGFBP-3 in the context of allergic airway disease, and discusses the therapeutic potential of various strategies targeting the IGF-I and IGFBP-3 signaling pathways for the management of asthma. PMID- 24219513 TI - What practices do parents perceive as effective or ineffective in promoting a healthy diet, physical activity, and less sitting in children: parent focus groups. AB - BACKGROUND: To support parents in improving the health of their young children, examples of effective parenting practices for a healthy diet, physical activity (PA) and sedentary behavior (SB) are needed. This study explores perceived effective and ineffective parenting practices in difficult situations concerning raising healthy children and investigates their relationship with Self Determination Theory (SDT) and Social Cognitive Theory (SCT). The current study is formative work to inform the content of a randomized controlled trial. METHODS: Four focus groups were conducted between June and October 2012 at worksites during lunch break. A total of 21 unrelated parents of primary schoolchildren (6 fathers, 15 mothers) participated. A short written questionnaire introduced typical difficult situations derived from parental anecdotal reports, concerning healthy diet, PA and SB. These situations formed the backbone for the subsequent focus group discussion. In October 2012, discussions were audio-recorded and analyzed in Nvivo to identify key response items using thematic analysis. RESULTS: Parents experienced explaining why the child should behave healthily, monitoring, being consistent, offering alternatives, reacting empathetically, modeling, motivating, increasing intrinsic value and availability, and using time-out as effective practices, whereas anger was considered ineffective. Opinions were mixed about the effectiveness of giving as much freedom as possible, obliging, rewarding and punishing, and setting rules and agreements. Parenting practices were consistent with principles from both SDT and SCT. CONCLUSIONS: Parents identified numerous perceived effective practices to respond to their child's health-related behavior. Since many of them coincide with the evidence base and the success of a parenting program depends upon the degree to which parents' concerns and motivations are integrated into the program design, important opportunities are created for future intervention programs. PMID- 24219506 TI - Sucralose, a synthetic organochlorine sweetener: overview of biological issues. AB - Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound. PMID- 24219516 TI - Evidence-guided education. PMID- 24219515 TI - Effects of direct-fed microbial supplementation on broiler performance, intestinal nutrient transport and integrity under experimental conditions with increased microbial challenge. AB - 1. The effects of Aspergillus oryzae- and Bacillus subtilis-based direct-fed microbials (DFM) were investigated on the performance, ileal nutrient transport and intestinal integrity of broiler chickens, raised under experimental conditions, with increased intestinal microbial challenge. 2. The first study was a 3 * 2 factorial experiment, with 3 dietary treatments (control (CON), CON + DFM and CON + antibiotic growth promoter) with and without challenge. Chicks were fed experimental diets from 1 to 28 d, while the challenge was provided by vaccinating with 10 times the normal dose of commercial coccidial vaccine on d 9. In a second experiment, two groups of 1 d-old broilers, housed on built-up litter (uncleaned from two previous flocks), were fed the same CON and CON + DFM diets from 1 to 21 d. 3. The challenge in the first experiment reduced performance, but no differences were observed among dietary treatments from 8 to 28 d. The challenge reduced the ileal epithelial flux for D-glucose, L-lysine, DL methionine and phosphorus on d 21. Epithelial flux for D-glucose, L-lysine and DL methionine were increased by DFM. Ileal trans-epithelial electrical resistance (TER) was increased in challenged broilers fed DFM, although this was not observed in unchallenged birds as indicated by a significant interaction. 4. Ileal mucin mRNA expression and colon TER were increased, and colon endotoxin permeability was reduced by DFM on d 21 in the second experiment. 5. It was concluded that the addition of DFM in the diet improved the intestinal integrity of broiler chickens raised under experimental conditions designed to provide increased intestinal microbial challenge. PMID- 24219517 TI - Tandem clerking: maximising workplace learning. AB - BACKGROUND: Medical assessment units (MAUs) are a valuable source of educational opportunities, but these are often not realised because of service pressures. We trialled a method of collaborative working, where junior and senior trainees work in 'tandem' to see new admissions. The roles are alternated throughout the shift with the aim of encouraging shared decisions, learning and feedback. METHODS: A 4 month trial of tandem clerking was implemented. An anonymous questionnaire of junior doctors collected quantitative and qualitative data to assess educational aspects of tandem clerking in the MAU of a busy district general hospital. RESULTS: Junior doctors (n = 14) report seeing a larger number and wider variety of patients using tandem clerking, with more useful feedback and a greater chance of meeting learning objectives and completing assessments. Some respondents expressed concern over a lack of autonomy. Respondents stated they were less likely to spend time completing mundane and non-educational tasks. Eight respondents preferred the new system, four favoured the traditional system and two had no preference. DISCUSSION: Tandem clerking is an innovative method to increase the educational aspects of the assessment unit, both in terms of feedback opportunities and exposure to a wider variety of patients. The technique is partly dependent on the enthusiasm and interest of both parties. PMID- 24219518 TI - Encouraging new doctors to do medical education research. AB - BACKGROUND: An academic foundation programme in medical education may allow junior medical trainees to gain experience in teaching and medical education research. After 2 years, three trainees will have completed the programme, and three more will be halfway through it. The authors explore problems encountered and how trainees maximised their experience, helping to inform future planning. SUMMARY OF WORK: Semi-structured group discussions covering trainees' experiences were conducted in the summer of 2011. All six trainees in the programme participated. SUMMARY OF RESULTS: Both site-specific and general issues were raised, most of which were dealt with in a pragmatic fashion. The trainees' goals and subsequent achievements varied. Important factors for trainees and those supervising them, and the organisation of the programme, are discussed. CONCLUSIONS: Our experience is that an academic foundation programme in medical education can be successful. This requires collaboration between trainees and supervisors. TAKE-HOME MESSAGE: The role of the academic supervisor in medical education research is key, but those involved in the practicalities of helping trainees maintain their protected research time is just as important. PMID- 24219519 TI - Maximising the value from the elective experience: post-elective workshops. AB - BACKGROUND: Medical electives are important facets of Global Health education of UK medical students, preparing them for work in an increasingly globalised world. However, their explicit educational value is unclear, and is often lost because of inadequate preparation and review procedures. METHOD: Aiming to capitalise on this unique personal and professional development opportunity, which Newcastle University students undertake in their fourth year, a pilot feedback workshop was designed in which 42 final-year students gave 10-15-minute reflective presentations to subgroups of between six and eight peers, followed by an opportunity for questions, discussion and feedback. Feedback was sought from individual questionnaires and then there was open discussion with the whole group. RESULTS: Despite the participants' variable satisfaction with the pre elective procedures, all felt that the elective itself was valuable and enjoyable, and, moreover, all enjoyed and benefited from debriefing in this workshop format. DISCUSSION: This pilot was successful. Simple, inexpensive workshops are to be recommended for overcoming perceived staffing and timetabling barriers to Global Health education, and affording students the maximum personal and professional benefit from their own, and each others' medical electives. PMID- 24219520 TI - An advanced quality improvement and patient safety elective. AB - BACKGROUND: Practising doctors must be competent in quality improvement (QI) and patient safety (PS). Despite this need, QI and PS have yet to be fully integrated into the undergraduate medical curriculum. Furthermore, there are few resources available for motivated senior medical students to receive advanced training prior to starting residency. To address these needs, we piloted an elective in QI/PS for senior medical students. METHODS: We measured changes in knowledge, attitude and QI/PS skills with before and after surveys and skill assessments. Post-elective measures included an assessment of reaction to the curriculum and an assessment of a QI project proposal. RESULTS: Six students participated in two 2-week electives. Mean knowledge test scores improved after the elective [mean score (SD)]: before, 7.3 (1.4), versus after, 8.2 (0.4); p = 0.19. There were improvements in confidence in all aspects queried, and this was significant in six of the seven confidence questions. Students had high motivation for future QI/PS involvement both before and after the elective. Validated measures assessing QI/PS skills showed high levels of performance both before and after the elective. Experiential components of the elective were most highly valued. DISCUSSION: Motivated students may not have the confidence needed to effectively actuate their desire to incorporate QI/PS in their continuing training and careers. This 2-week elective significantly improved students' confidence and maintained their motivation for QI/PS work. Experiential activities may be particularly beneficial for students to learn QI/PS throughout medical school. PMID- 24219521 TI - Providing a specialty trainee teaching programme over long distances. AB - BACKGROUND: Today's teaching programmes must be interesting, relevant to the surgical curriculum, as defined in the UK by the Intercollegiate Surgical Curriculum Programme (ISCP), and attractive enough to the trainee so that they encourage attendance without compromising operative experience. METHODS: Our aim was to achieve the objectives of the ISCP and to provide high-quality teaching to the trainees. We devised a 2-year rolling programme of events to cover the knowledge and skills required for general surgical training for both the Membership of the Royal College of Surgeons (MRCS) and Fellowship of the Royal College of Surgeons (FRCS) examinations. For the trainees unable to attend because of on-call commitments, we developed online course material, creating our own virtual learning environment (VLE). Attendance at training days, website use and exam pass rates were monitored. We surveyed trainees annually to identify whether the teaching was meeting their needs. RESULTS: There were 100 per cent pass rates for FRCS clinical and viva examinations, with 16 out of the 16 candidates passing on their first attempt and one gold medal awarded. DISCUSSION: Our attendance rates show that it is possible to provide well-attended sessions despite modern working patterns. The production of a yearly teaching plan with identified topics and dates allowed trainees to maximise their attendance. PMID- 24219522 TI - Learning trajectories in longitudinal rural medical school placements. AB - BACKGROUND: Rural longitudinal placements are now a key part of clinical medical education, and are part of workforce strategies to enhance the rural medical workforce. Learning trajectories (a map to guide student learning) have been recommended as a means of maximising student learning on placements, and have the potential to assist long-term rural students and supervisors in adapting to a longitudinal clerkship. CONTEXT: This study focuses on year-3 medical students in rural longitudinal clinical placements at an Australian graduate-entry medical school. INNOVATION: This article reports the outcomes of working with current rural supervisors and students to develop a learning trajectory across the rural stream year, for implementation in future years. IMPLICATIONS: Students and supervisors identified incremental learning goals in keeping with Dreyfus's model of progressive skill development. Students offered tips to future students to adjust to variations in learning experiences across rural sites. Some supervisors were reluctant to have a learning trajectory, fearing it would be seen as proscriptive and reduce student ambition for varied rich experiences. Future research will focus on the impact of the rural learning trajectory. PMID- 24219523 TI - Mental health care training for practitioners in remote and rural areas. AB - BACKGROUND: Rural and island health care staff in Scotland are required to manage patients experiencing mental health crises. To ensure practitioners in remote and rural areas have the necessary skills, the Remote and Rural Healthcare Educational Alliance (RRHEAL) were asked to develop a pre-hospital mental health care course. METHODS: Several mental health care experts were asked to express an opinion on the essential content of such a course. Stakeholder review informed the development of a survey to identify the priority areas for training. The first round of the survey process involved an expert group of 16; the second round used a survey of over 300 remote and rural practitioners involved with the British Association for Immediate Care, Scotland (BASICS). RESULTS: The stakeholder review identified key content, summarised under the following topics: risk assessment; patient assessment; crisis management; handling difficult situations; engagement skills; mental health law; management of retrieval; pharmacology; theory and classification of mental illness; and understanding your network. DISCUSSION: This article shares how the needs within a national pre hospital mental health care programme were identified, and demonstrates how consensus over the content of a national course was achieved through the use of a modified Delphi approach. The Clinical Skills Managed Educational Network (CSMEN), Self-Harm Mitigation Training (STORM(r)) and BASICS, alongside RRHEAL, contributed to this development. Using blended learning techniques the resulting course encourages a contextual approach to user needs, specifically teaching generic mental health care skills to staff who are often working single-handed, and are required to respond appropriately, locally and safely as they work towards achieving National Mental Health crisis standards. PMID- 24219524 TI - Teaching wilderness and outdoor medicine in a city. AB - BACKGROUND: Teaching medical students wilderness medicine helps students learn how to apply skills such as leadership, teamwork and managing medical emergencies. The literature contains papers that describe methods for delivering this type of teaching, but they use specialised centres and a significant number of tutors. This paper describes a course delivered within the university and a nearby outdoor centre. METHODS: A course that covered outdoor emergency skills, and expedition and leadership skills, was delivered to third-year medical students. The usefulness of the course was assessed using student and tutor evaluations and the end-of-course assessment results. Practical scenarios were used to stimulate learning and the course finished with a camping trip, during which the students had to manage injuries in the field. RESULTS: The course was successfully delivered using only two tutors. The results of the evaluations indicated that the students had gained a good knowledge of the areas covered; they enjoyed the course and were able to apply first-aid skills to the outdoor situation. The students especially liked the approach of using practical scenarios to help them apply the principles that they had learned in the course. DISCUSSION: The course was successful because of the use of scenarios that encouraged the students to actively manage casualties and work as a team. We were able to deliver the course at a reasonable cost by using the facilities of a local outdoor camping centre. PMID- 24219525 TI - Annual review of competence: trainees' perspective. AB - BACKGROUND: An annual review of competence progression (ARCP) is compulsory for all UK specialty trainees. AIM: We explore specialty trainees' views on ARCPs, including the usefulness of annual review, and how well prepared they felt for it. METHODS: A 15-item questionnaire was completed anonymously by 63 paediatric specialty trainees following their ARCPs in the West Midlands Deanery. After further trainee and trainer education on ARCPs, 21 trainees participated in telephone semi-structured interviews. RESULTS: Seventy-six per cent of paediatric specialty trainees found having an ARCP helpful, although 70 per cent did not feel well informed about the process: this did not vary by training year or gender. Apart from trainees valuing a regional review of progress, the other key themes from the semi-structured interviews were negative around ePortfolio, IT, lack of consultant training and willingness to undertake assessments, being unaware of the evidence needed for ARCP and electronic ARCP feedback. CONCLUSION: Although three-quarters of paediatric trainees found having an ARCP helpful, they did not feel prepared for the ARCP. Educating both trainees and trainers about ARCPs and the required portfolio evidence is continuing; however, we believe trainees will only truly feel prepared for their ARCPs after successfully addressing the more challenging issues of good IT infrastructure in each trust, with consultants readily undertaking workplace-based assessments (WBAs) and with educational supervision being of a consistently high standard. PMID- 24219527 TI - The olfactory examination: a waft of disease. PMID- 24219528 TI - The hidden value of a mock OSCE. PMID- 24219526 TI - Student perception of workplace-based assessment. AB - BACKGROUND: Workplace-based assessment (WPBA) is key to medical education, providing a framework through which the trainee can be assessed and receive feedback in the clinical setting. WPBA was introduced in 2008-2009 to students in year 4 at University College London Medical School (UCLMS). Students raised concerns about the lack of standardisation in grading. As a result, white-space areas were introduced on WPBA forms. The aim of this was to permit assessors to expand their feedback, thereby enhancing its developmental potential. The aim of the project was to assess student perception of WPBA at UCLMS, and to determine whether re-designing the form had altered this perception. METHOD: An online survey was circulated to students in year 4 at the end of the academic year 2009 2010, and was repeated with the next cohort of year-4 students at the end of the academic year 2010-2011. Students were asked to express a level of agreement with 12 statements and for free-text comments on their experience with WPBA. Survey responses were analysed using an unpaired two-tailed Student's t-test, and QSR NVivo was used to manage the thematic analysis of the free-text comments. RESULTS: Although there was no significant difference in student perception between cohorts, the analysis of free-text comments highlighted several themes for discussion. CONCLUSION: Students at UCLMS find WPBA valuable in highlighting areas for improvement and obtaining personalised feedback. They find the grading of WPBA too subjective, and that the attitudes of the assessors sometimes reduce its educational value. Suggestions are made to improve the value of WPBA in undergraduate medical education. PMID- 24219529 TI - Dealing with the unpredictable. PMID- 24219530 TI - Medical student research in Iran. PMID- 24219531 TI - Blueprinting. PMID- 24219537 TI - The utility of teaching ultrasonography. PMID- 24219538 TI - Utilising junior doctors in medical education. PMID- 24219539 TI - Role of arterial hypertension as a predictive marker for bevacizumab efficacy in recurrent glioblastoma - a prospective analysis. PMID- 24219540 TI - Grb2 and its influence on tumor growth and progression in systemic malignancies. PMID- 24219541 TI - Excess mortality in postmenopausal high-risk women who only receive adjuvant endocrine therapy for estrogen receptor positive breast cancer. AB - BACKGROUND: Omission of chemotherapy may affect mortality in postmenopausal high risk women despite appropriate adjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer. The aim of this study was to determine how all-cause mortality rate in these patients compares to that of the general female population. Furthermore, to identify a subset without excess mortality using clinical and pathological characteristics. PATIENTS AND METHODS: From the population-based database of the Danish Breast Cancer Cooperative Group we included 6529 postmenopausal patients with ER positive high-risk breast cancer who in 1996 through 2004 by nationwide guidelines were allocated to five years of tamoxifen, an aromatase inhibitor (AI) or both in sequence. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics. RESULTS: In a multivariate model excess mortality was inversely (p < 0.0001) associated with increasing age at surgery while recurrence-free survival (RFS) was not. Non adherence to endocrine therapy was associated with excess mortality (p = 0.0008) while treatment with an AI was associated with a less pronounced mortality excess (p = 0.03). A prognostic standard mortality rate (SMR) index (PSI) was built using the regression coefficients obtained in the MFP model, and the same risk factors were used to construct a flowchart algorithm. Both allocated 75% to a group with increased all-cause mortality as compared to the general female population, but the SMR was significantly increased (SMR 1.38; 95% CI 1.16-1.65) in 462 patients who were allocated to low-risk group by the Flowchart algorithm and to a high-risk group by PSI. CONCLUSION: Only one quarter of postmenopausal ER positive breast cancer patients are free of excess mortality when omitting adjuvant chemotherapy. Patients should be informed about importance of adherence to adjuvant endocrine therapy and inclusion of an AI. A PSI may better guide recommendations regarding adjuvant chemotherapy. PMID- 24219542 TI - Modeling continuous self-report measures of perceived emotion using generalized additive mixed models. AB - Emotion research has long been dominated by the "standard method" of displaying posed or acted static images of facial expressions of emotion. While this method has been useful, it is unable to investigate the dynamic nature of emotion expression. Although continuous self-report traces have enabled the measurement of dynamic expressions of emotion, a consensus has not been reached on the correct statistical techniques that permit inferences to be made with such measures. We propose generalized additive models and generalized additive mixed models as techniques that can account for the dynamic nature of such continuous measures. These models allow us to hold constant shared components of responses that are due to perceived emotion across time, while enabling inference concerning linear differences between groups. The generalized additive mixed model approach is preferred, as it can account for autocorrelation in time series data and allows emotion decoding participants to be modeled as random effects. To increase confidence in linear differences, we assess the methods that address interactions between categorical variables and dynamic changes over time. In addition, we provide comments on the use of generalized additive models to assess the effect size of shared perceived emotion and discuss sample sizes. Finally, we address additional uses, the inference of feature detection, continuous variable interactions, and measurement of ambiguity. PMID- 24219543 TI - Model comparisons using tournaments: likes, "dislikes," and challenges. AB - We examine the value added of tournaments that compare the predictive power of behavioral models. The advantages and disadvantages of this particular method have not been systematically discussed in the literature; here we aspire to do so. We conclude that tournaments are a useful addition to our arsenal of methods and a significant step forward in the study of the predictive power of behavioral models. Such tournaments are not without limitations, however, and we identify and illustrate current limitations, propose solutions to overcome some of them, and identify a research agenda to address the remaining. PMID- 24219544 TI - Longitudinal design considerations to optimize power to detect variances and covariances among rates of change: simulation results based on actual longitudinal studies. AB - We investigated the power to detect variances and covariances in rates of change in the context of existing longitudinal studies using linear bivariate growth curve models. Power was estimated by means of Monte Carlo simulations. Our findings show that typical longitudinal study designs have substantial power to detect both variances and covariances among rates of change in a variety of cognitive, physical functioning, and mental health outcomes. We performed simulations to investigate the interplay among number and spacing of occasions, total duration of the study, effect size, and error variance on power and required sample size. The relation between growth rate reliability (GRR) and effect size to the sample size required to detect power greater than or equal to .80 was nonlinear, with rapidly decreasing sample sizes needed as GRR increases. The results presented here stand in contrast to previous simulation results and recommendations (Hertzog, Lindenberger, Ghisletta, & von Oertzen, 2006; Hertzog, von Oertzen, Ghisletta, & Lindenberger, 2008; von Oertzen, Ghisletta, & Lindenberger, 2010), which are limited due to confounds between study length and number of waves, error variance with growth curve reliability, and parameter values that are largely out of bounds of actual study values. Power to detect change is generally low in the early phases (i.e., first years) of longitudinal studies but can substantially increase if the design is optimized. We recommend additional assessments, including embedded intensive measurement designs, to improve power in the early phases of long-term longitudinal studies. PMID- 24219546 TI - Using induced human pluripotent stem cells to study Diamond-Blackfan anemia: an outlook on the clinical possibilities. PMID- 24219547 TI - 1:1:1 - Warranted or wasteful? Even where appropriate, high ratio transfusion protocols are costly: early transition to individualized care benefits patients and transfusion services. PMID- 24219545 TI - Regulation of Na(+)/K(+)-ATPase by neuron-specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons. AB - A major source of energy demand in neurons is the Na(+)/K(+)-ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase (COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron-specific Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na(+)/K(+)-ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over-expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na(+)/K(+)-ATPase in neurons. Transcripts of all three genes were up-regulated by depolarizing KCl stimulation and down regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity-dependent. Silencing of Sp4 blocked the up-regulation of these genes induced by KCl, whereas over-expression of Sp4 rescued them from TTX induced suppression. The effect of silencing or over-expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons. PMID- 24219549 TI - Special features of total knee replacement in hemophilia. AB - Total knee replacement is an operation frequently needed by hemophilia patients, which greatly improves their quality of life. This operation, however, carries a higher risk of bleeding and infection for hemophiliacs than it does for osteoarthritis sufferers. It is advisable to implant prosthetic components using antibiotic-loaded cement. It is essential to maintain a level of 100% of the replacement clotting factor for 2 weeks. Hematological treatment must be established, depending on the patient's factor levels and other pharmacokinetic parameters such as recovery and half-life, optimal doses and treatment time. It is preferable to use general anesthesia due to the risk of spinal bleeding. The lifespan of total knee replacement in hemophilic patients is shorter than in patients with osteoarthritis because of the increased risk of infection. PMID- 24219551 TI - Treatment approaches to asymptomatic follicular lymphoma. AB - Follicular lymphoma is a heterogeneous disease in which some patients present an indolent evolution for decades and others, a rather aggressive form of the disease requiring immediate therapy. While immunochemotherapy has emerged as a standard of care for symptomatic patients, treatment of the asymptomatic population remains controversial. Since the disease is still considered incurable, delayed initiation of therapy is an acceptable option. However, four single injections of rituximab can result in an acceptable clinical response and can improve the duration of the interval without cytotoxic therapy. With recent therapeutic approaches that enable substantial improvements in life expectancy for follicular lymphoma patients, limiting short- or long-term treatment toxicities appears as a new concern in the asymptomatic population. Based on these options, the challenge is to preserve patient quality of life and prolong survival: from the patient's perspective, his/her opinion is therefore of significant importance. PMID- 24219552 TI - Is there a role for allogeneic transplantation in chronic myeloid leukemia? AB - Allogeneic hemopoietic cell transplantation has moved away from being the standard of care for patients with chronic myeloid leukemia (CML). Its role is currently limited to an unsatisfactory response to therapy with tyrosine kinase inhibitors as well as advanced stages of the disease. The advent of tyrosine kinase inhibitors has been one of the most remarkable advances in any form of cancer. Never-the-less, as a definitive procedure, allogeneic transplantation remains the only curative modality and its use in carefully selected patients, who have an inadequate response, has been increasingly recognized. It remains a standard of care for patients who present with blast crisis CML and is often used also in accelerated phase. The future for patients with CML has become so much brighter over the past decade but new issues and considerations continually emerge. PMID- 24219550 TI - The use of novel oral anticoagulants for thromboprophylaxis after elective major orthopedic surgery. AB - Venous thromboembolism is a common cause of morbidity and mortality among patients undergoing elective orthopedic surgery. Due to the high incidence of venous thromboembolism in this setting, perioperative anticoagulation is the recommended approach for thromboprophylaxis. Low molecular weight heparin (LMWH), fondaparinux and warfarin are the agents commonly used for thromboprophylaxis. The well-recognized limitations of warfarin and the inconvenience and discomfort associated with the subcutaneous administration of low molecular weight heparin and fondaparinux inspired intense investigation to develop novel oral anticoagulants (NOACs) with more predictable pharmacokinetics, fewer drug interactions and no need for regular laboratory monitoring. Three NOACs have been demonstrated to be effective for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in large randomized controlled trials. Here we review the pharmacology of rivaroxaban, dabigatran, and apixaban, summarize the major clinical trials of these agents in thromboprophylaxis after THA and TKA, and discuss the clinical factors to be considered by providers when selecting a NOAC for their patients. PMID- 24219553 TI - Alternative novel therapies for the treatment of elderly acute myeloid leukemia patients. AB - With a median age at diagnosis of approximately 65-70 years, acute myeloid leukemia (AML) represents a major therapeutic challenge in the elderly. Only 30 35% of elderly patients with AML are considered eligible for intensive chemotherapy and do actually receive it. However, the long-term benefit associated with intensive chemotherapy remains marginal, and the overall outcome for this population remains poor. The remaining 60-65% of elderly AML patients receives supportive care only. Nevertheless, several studies have indicated that patients who receive any therapy had a better outcome if compared with patients who receive supportive care only. Thus, the development of novel, less toxic, targeted agents is offering new options to older AML patients who are unfit for intensive approaches. In the present review, we will report on the results achieved using intensive chemotherapy and novel agents, and will describe some of the new strategies under development for treating older AML patients. PMID- 24219554 TI - Rejection sensitivity and vulnerability to self-directed hostile cognitions following rejection. AB - We examined the hypothesis that rejection increases self-directed hostile cognitions in individuals who are high in rejection sensitivity (RS). In four studies employing primarily undergraduate samples (Ns = 83-121), rejection was primed subliminally or through a recall task, and self-directed hostile cognitions were assessed using explicit or implicit measures. Negative or neutral control conditions were used in three of the studies. Measures of RS were obtained in pretesting. High RS participants were more likely than low RS participants to report or show greater self-directed hostile cognitions in rejection conditions, compared to control conditions. Results held when controlling for depressive symptoms, history of self-directed hostile cognitions, and general hostility. RS may represent a unique vulnerability for self-directed hostile cognitions, a predictor of self-harmful behavior. PMID- 24219555 TI - Adherence to pharmacological pain therapy in patients with nonmalignant pain: the role of patients' knowledge of pain medication. AB - BACKGROUND: Nonadherence to pharmacological therapy is a common and underexposed problem in patients with chronic nonmalignant pain. It may lead to treatment failure and increased healthcare costs. METHODS: In this prospective observational study we analyzed the association between knowledge and adherence in the chronic nonmalignant pain population. We included 96 patients treated with a new pharmacological prescription. During the initial visit (T0), demographic variables, pain intensity, knowledge of the prescription (name, dose, and frequency), self-reported adherence to the prescription, and general knowledge of pharmacological pain therapy (according to the Pain Knowledge Questionnaire, Dutch Language Version (PKQ-DLV) were recorded. During two follow-up visits (T1, T2), apart from demographics, these parameters were measured again. RESULTS: Adherence rates were 42%, 42%, and 46% at T0, T1 and T2, respectively. 53%, 59%, and 48% of patients had knowledge of their current prescription, and mean scores on the PKQ-DLV were 56, 55, and 52 percent of the maximum scores, respectively, at T0, T1 and T2. A multivariate binary logistic regression analysis resulted in a significant contribution of knowledge of the prescription and of age to the prediction of adherence. CONCLUSIONS: Knowledge of the analgesic prescription is associated with adherence and significantly contributes to the prediction of adherence to analgesic therapy. An interventional study is needed to determine whether increasing knowledge will improve medication adherence and therapy outcome in patients with chronic nonmalignant pain. PMID- 24219556 TI - Activation of peroxisome proliferator-activated receptor gamma leads to upregulation of ESE-3 expression in human monocyte-derived dendritic cells. AB - The transcription factor ESE-3 has been suggested to be involved in regulating the immunogenicity of human monocyte-derived dendritic cells (moDCs). While ESE-3 is not expressed in monocytes, it is upregulated during the differentiation of monocytes into dendritic cells (DCs) and highly expressed in immunogenic DCs while downregulated in tolerogenic DCs. Activation of peroxisome proliferator activated receptor gamma (PPAR-gamma) during DC development has been shown to result in a rather tolerogenic cell population. In this study, we identified eight PPAR-gamma binding sites upstream of the ESE-3 gene. Activation of the PPAR gamma pathway with synthetic PPAR-gamma ligands during moDC generation resulted in upregulation of ESE-3b expression on mRNA and protein level, phenotypic alterations and reduced capacity of the cells to stimulate allogeneic T cells. This could be inhibited by blocking the PPAR-gamma pathway with specific antagonists. Our results suggest PPAR-gamma to be involved in the regulation of ESE-3b expression during moDC development and that ESE-3 expression is not correlated with the immunogenicity of DCs. PMID- 24219557 TI - Prolonged postdiapause: influence on some indicators of carbohydrate and lipid metabolism of the red mason bee, Osmia rufa. AB - Bees of the genus Osmia are being used in crop pollination at an increasing rate. However, a short life expectancy of adult individuals limits the feasibility of their use. Cocoons of the red mason bee, Osmia rufa L. (Hymenoptera: Megachilidae), can be stored at 4 degrees C in a postdiapause state, and adult bees can be used for pollination outside their natural flight period. The period of storage in this form has an unfavorable influence on the survival rate, life expectancy, and fertility of the bee. It was suggested that the negative results are connected with exhaustion of energy reserves. To test this hypothesis, the present study examined the contents of protein, carbohydrates, lipids, and the activities of some enzymes, and their degradation in red mason bees that emerged in spring according to their biological clock and in summer after elongated diapause. It was found that postdiapause artificially elongated by 3 months caused significant decreases in body weight, total sugar, glycogen, lipids, and protein content in O. rufa. Glucose level was highest in bees that emerged in the summer, which was coincident with increased activities of maltase and trehalase. The activities of sucrase and cellobiase were not changed, while amylase activity was considerably decreased. The activities of triacylglycerols lipase and C2, C4, C10 carboxylesterases were highest in bees that emerged in July. Low temperatures restrict O. rufa emergence, and during prolonged postdiapause, metabolic processes lead to significant reductions of structural and energetic compounds. PMID- 24219558 TI - Understanding the mechanism of polymerization of epsilon-caprolactone catalyzed by aluminum salen complexes. AB - Studies of the kinetics of polymerization of epsilon-caprolactone (CL) by salen aluminum catalysts comprising ligands with similar steric profiles but different electron donating characteristics (R = OMe, Br, or NO2) were performed using high initial monomer concentrations (2 M < [CL]0 < 2.6 M) in toluene-d8 at temperatures ranging from 20 to 90 degrees C. Saturation behavior was observed, enabling determination of monomer equilibrium constants (Keq) and catalytic rate constants (k2) as a function of R and temperature. While Keq varied only slightly with the electron donating properties of R (Hammett rho = +0.16(8)), k2 showed a more significant dependence reflected by rho = +1.4(1). Thermodynamic parameters DeltaG degrees (associated with Keq) and DeltaG(?) (associated with k2) were determined, with the former being ~0 kcal/mol for all catalysts and the latter exhibiting the trend R = OMe > Br > NO2. Density functional theory (DFT) calculations were performed to characterize mechanistic pathways at a microscopic level of detail. Lowest energy transition-state structures feature incipient bonding of the nucleophile to the lactone carbonyl that is approaching the metal ion, but a distinct CL adduct is not an energy minimum on the reaction pathway, arguing against Keq being associated with coordination of monomer according to the typical coordination-insertion mechanism. An alternative hypothesis is presented associating Keq with "nonproductive" coordination of substrate in a manner that inhibits the polymerization reaction at high substrate concentrations. PMID- 24219559 TI - Cerebral dysfunction in children: should this be the central tenet for a new system of classification? PMID- 24219560 TI - Interpreting chiral nanophotonic spectra: the plasmonic Born-Kuhn model. AB - One of the most intuitive ways to classically understand the generation of natural optical activity in chiral media is provided by the coupled oscillator model of Born and Kuhn consisting of two identical, vertically displaced, coupled oscillators. We experimentally realize and discuss its exact plasmonic analog in a system of corner-stacked gold nanorods. In particular, we analyze the arising circular dichroism and optical rotatory spectra in terms of hybridized electromagnetic modes and retardation. Specifically, we demonstrate how tuning the vertical distance between the nanorods can lead to a selective excitation of the occurring bonding and antibonding chiral plasmonic modes. PMID- 24219561 TI - Optimisation and standardisation of an immunoagglutination assay for the diagnosis of Trypanosoma cruzi infection based on latex-(recombinant antigen) complexes. AB - OBJECTIVE: To determine the conditions under which the immunoagglutination assay to detect Chagas disease, obtained from a novel latex-(chimeric recombinant antigen) complex, shows greater discrimination between the responses of a positive control serum and a negative control serum. METHODS: The following variables were determined: (i) the sensitisation mechanism, (ii) the emulsifier employed for protein desorption, (iii) the reaction time, (iv) the ionic strength of the reaction medium, (v) the particle concentration, (vi) the presence of blocking agents, (vii) the presence of polyethyleneglycol as potentiator of reaction and (viii) the antigen and antibody concentrations. The search of optimal conditions was investigated by varying one variable at a time. To this effect, monodisperse latex particles sensitised with a recombinant chimeric protein (CP1) were subjected to different conditions. The agglutination reaction was followed by measuring the changes in the optical absorbance by turbidimetry. RESULTS: The maximum discrimination between negative and positive sera was obtained at a reaction time of 5 min, when latex complexes with a concentration of covalently coupled protein of 2.90 mg/m(2) were put in contact with undiluted sera in buffer borate pH 8-20 mm containing glycine (0.1 m) and polyethyleneglycol 8000 (3% w/v). Finally, the latex-protein complex was tested under the obtained optimal conditions, with a panel of Trypanosoma cruzi-positive sera, leishmaniasis-positive sera and -negative sera for both parasites. CONCLUSION: The immunoagglutination test based on the latex-CP1 complex could be used as a screening method for detecting Chagas disease. This test is rapid, easy to implement and could be used under field conditions; but its results should be confirmed by reference techniques like ELISA, HAI, and IFI. PMID- 24219563 TI - Optical spectra and band structure of Ag(x)Ga(x)Ge(1-x)Se2 (x = 0.333, 0.250, 0.200, 0.167) single crystals: experiment and theory. AB - Theoretical and experimental studies of the Ag(x)Ga(x)Ge(1-x)Se2 (x = 0.333, 0.250, 0.200, 0.167) single crystals are performed. These crystals possess a lot of intrinsic defects which are responsible for their optoelectronic features. The theoretical investigations were performed by means of DFT calculations using different exchange-correlation potentials. The experimental studies were carried out using the modulated VUV ellipsometry for dielectric constants and birefringence studies. The comparison of the structure obtained from X-ray with the theoretically optimized structure is presented. The crucial role of the intrinsic defect states is manifested in the choice of the exchange correlation potential used. The data may be applicable for a large number of the ternary chalcogenides which are sensitive to the presence of the local disordered states near the band edges. PMID- 24219562 TI - Comparative genomics reveals candidate carotenoid pathway regulators of ripening watermelon fruit. AB - BACKGROUND: Many fruits, including watermelon, are proficient in carotenoid accumulation during ripening. While most genes encoding steps in the carotenoid biosynthetic pathway have been cloned, few transcriptional regulators of these genes have been defined to date. Here we describe the identification of a set of putative carotenoid-related transcription factors resulting from fresh watermelon carotenoid and transcriptome analysis during fruit development and ripening. Our goal is to both clarify the expression profiles of carotenoid pathway genes and to identify candidate regulators and molecular targets for crop improvement. RESULTS: Total carotenoids progressively increased during fruit ripening up to ~55 MUg g(-1) fw in red-ripe fruits. Trans-lycopene was the carotenoid that contributed most to this increase. Many of the genes related to carotenoid metabolism displayed changing expression levels during fruit ripening generating a metabolic flux toward carotenoid synthesis. Constitutive low expression of lycopene cyclase genes resulted in lycopene accumulation. RNA-seq expression profiling of watermelon fruit development yielded a set of transcription factors whose expression was correlated with ripening and carotenoid accumulation. Nineteen putative transcription factor genes from watermelon and homologous to tomato carotenoid-associated genes were identified. Among these, six were differentially expressed in the flesh of both species during fruit development and ripening. CONCLUSIONS: Taken together the data suggest that, while the regulation of a common set of metabolic genes likely influences carotenoid synthesis and accumulation in watermelon and tomato fruits during development and ripening, specific and limiting regulators may differ between climacteric and non climacteric fruits, possibly related to their differential susceptibility to and use of ethylene during ripening. PMID- 24219564 TI - Incidence of soft tissue sarcomas in an Italian area affected by illegal waste dumping sites. AB - The aim of the present study was to investigate the possible association between occurrence of soft tissue sarcomas (STS) and residence in an Italian area affected by illegal practices of dumping and setting fire to both hazardous and solid urban wastes. Standardized incidence ratios (SIRs) were computed separately for STS and some specific STS subtypes. The analysis was performed for the total population and for specific age groups, namely, children, adolescents, and adults. In adults, no significant increase in STS was found other than for gastrointestinal stromal tumors in males. A nonsignificant increase in incidence of STS was observed for male children and female adolescents. The results of the present study do not allow conclusions for a causal association. In the absence of previous epidemiological studies on this issue, further investigations are needed. PMID- 24219565 TI - Evaluation of p21 promoter for interleukin 12 radiation induced transcriptional targeting in a mouse tumor model. AB - BACKGROUND: Radiation induced transcriptional targeting is a gene therapy approach that takes advantage of the targeting abilities of radiotherapy by using radio inducible promoters to spatially and temporally limit the transgene expression. Cyclin dependent kinase inhibitor 1 (CDKN1A), also known as p21, is a crucial regulator of the cell cycle, mediating G1 phase arrest in response to a variety of stress stimuli, including DNA damaging agents like irradiation. The aim of the study was to evaluate the suitability of the p21 promoter for radiation induced transcriptional targeting with the objective to test the therapeutic effectiveness of the combined radio-gene therapy with p21 promoter driven therapeutic gene interleukin 12. METHODS: To test the inducibility of the p21 promoter, three reporter gene experimental models with green fluorescent protein (GFP) under the control of p21 promoter were established by gene electrotransfer of plasmid DNA: stably transfected cells, stably transfected tumors, and transiently transfected muscles. Induction of reporter gene expression after irradiation was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging using fluorescence stereomicroscope in vivo. The antitumor effect of the plasmid encoding the p21 promoter driven interleukin 12 after radio-gene therapy was determined by tumor growth delay assay and by quantification of intratumoral and serum levels of interleukin 12 protein and intratumoral concentrations of interleukin 12 mRNA. RESULTS: Using the reporter gene experimental models, p21 promoter was proven to be inducible with radiation, the induction was not dose dependent, and it could be re-induced. Furthermore radio-gene therapy with interleukin 12 under control of the p21 promoter had a good antitumor therapeutic effect with the statistically relevant tumor growth delay, which was comparable to that of the same therapy using a constitutive promoter. CONCLUSIONS: In this study p21 promoter was proven to be a suitable candidate for radiation induced transcriptional targeting. As a proof of principle the therapeutic value was demonstrated with the radio-inducible interleukin 12 plasmid providing a synergistic antitumor effect to radiotherapy alone, which makes this approach feasible for the combined treatment with radiotherapy. PMID- 24219566 TI - Role of N-vinyl-2-pyrrolidinone on the thermoresponsive behavior of PNIPAm hydrogel and its release kinetics using dye and vitamin-B12 as model drug. AB - Temperature-sensitive hydrogels hold great promise in biological applications as they can respond to changes in physiological temperature to produce a desired effect like controlled drug delivery. In this study, a series of poly(N isopropylacrylamide-co-N-vinyl-2-pyrrolidinone) thermosensitive hydrogels were synthesized by radical copolymerization of NIPAm with 1-vinyl-2-pyrrolidinone (NVP). By altering the initial NIPAm/NVP mole ratios, copolymers were synthesized to have their own distinctive lower critical solution temperature which was established using differential scanning calorimetry. The swelling behavior of the hydrogel was analyzed gravimetrically and it was observed that reswelling rate increases with increasing NVP mole ratio. Further characterizations of the hydrogels were performed using Fourier transform infrared spectroscopy and scanning electron microscopy. Release kinetics with respect to temperature was studied using methylene blue dye solution and vitamin B12. Kinetic modeling of the release profile revealed that the release mechanism is a non-Fickian diffusion mechanism. These results suggested that this material has potential application as intelligent drug carriers. The quantities of residual monomers in the PIV4 hydrogel were determined by HPLC method, and the results show almost complete conversion. PMID- 24219567 TI - Water and beverage consumption among adults in the United States: cross-sectional study using data from NHANES 2005-2010. AB - BACKGROUND: Few studies have examined plain water consumption among US adults. This study evaluated the consumption of plain water (tap and bottled) and total water among US adults by age group (20-50y, 51-70y, and >=71y), gender, income-to poverty ratio, and race/ethnicity. METHODS: Data from up to two non-consecutive 24-hour recalls from the 2005-2006, 2007-2008 and 2009-2010 National Health and Nutrition Examination Survey (NHANES) was used to evaluate usual intake of water and water as a beverage among 15,702 US adults. The contribution of different beverage types (e.g., water as a beverage [tap or bottled], milk [including flavored], 100% fruit juice, soda/soft drinks [regular and diet], fruit drinks, sports/energy drinks, coffee, tea, and alcoholic beverages) to total water and energy intakes was examined. Total water intakes from plain water, beverages, and food were compared to the Adequate Intake (AI) values from the US Dietary Reference Intakes (DRI). Total water volume per 1,000 kcal was also examined. RESULTS: Water and other beverages contributed 75-84% of dietary water, with 17 25% provided by water in foods, depending on age. Plain water, from tap or bottled sources, contributed 30-37% of total dietary water. Overall, 56% of drinking water volume was from tap water while bottled water provided 44%. Older adults (>=71y) consumed much less bottled water than younger adults. Non-Hispanic whites consumed the most tap water, whereas Mexican-Americans consumed the most bottled water. Plain water consumption (bottled and tap) tended to be associated with higher incomes. On average, younger adults exceeded or came close to satisfying the DRIs for water. Older men and women failed to meet the Institute of Medicine (IOM) AI values, with a shortfall in daily water intakes of 1218 mL and 603 mL respectively. Eighty-three percent of women and 95% of men >=71y failed to meet the IOM AI values for water. However, average water volume per 1,000 kcal was 1.2-1.4 L/1,000 kcal for most population sub-groups, higher than suggested levels of 1.0 L/1.000 kcal. CONCLUSIONS: Water intakes below IOM recommended levels may be a cause for concern, especially for older adults. PMID- 24219568 TI - Management of mediastinal syndromes in pediatrics: a new challenge of ultrasound guidance to avoid high-risk general anesthesia. AB - Adverse events associated with anesthetic management of anterior mediastinal masses in pediatrics are common. To avoid an extremely hazardous general anesthesia, the use of real-time ultrasonography offers an effective alternative in high-risk cases. We report the anesthetic management including a light sedation and ultrasound guidance for regional anesthesia, surgical node biopsy, and placement of a central venous line in two children with an anterior symptomatic mediastinal mass. For pediatric patients with clinical and/or radiologic signs of airway compression, ultrasound guidance provides safety technical assistance to avoid general anesthesia and should be performed for the initial diagnostic and therapeutic procedures. PMID- 24219571 TI - Characterization of the key aroma compounds in two bavarian wheat beers by means of the sensomics approach. AB - Application of aroma extract dilution analysis (AEDA) on the volatiles isolated from a commercial Bavarian wheat beer (WB A) eliciting its typical aroma profile, best described by a clove-like, phenolic odor quality, revealed 36 odorants in the flavor dilution (FD) factor range from 16 to 4096. Among them, 2-methoxy-4 vinylphenol (clove-like) and 2-phenylethanol (flowery) showed the highest FD factors. AEDA of a second wheat beer (WB B), somewhat lacking the typical wheat beer odor note, revealed 32 odor-active components in the FD factor range from 32 to 8192. Among them, 2-phenylethanol, (E)-beta-damascenone (cooked apple-like) and 3-methylbutanol (malty) were detected with the highest FD factors. Next, all odorants evaluated with an FD factor >=32 were quantitated by stable isotope dilution assays in both beers, and the odor activity values (OAVs; ratio of concentration to odor threshold) were calculated. Thereby, ethanol, (E)-beta damascenone, 3-methylbutyl acetate, ethyl methylpropanoate, and ethyl butanoate showed the highest OAVs in WB A, followed by acetaldehyde, 3-methylbutanol, and dimethyl sulfide. In WB B, ethanol, (E)-beta-damascenone, ethyl methylpropanoate, ethyl butanoate, and 3-methylbutyl acetate showed the highest OAVs. Whereas most aroma compounds were present in the same order of magnitude in both beer samples, in particular, 2-methoxy-4-vinylphenol and 4-vinylphenol (smoky, leather-like) were by factors of 13 and 15, respectively, higher in WB A. For the first time, the overall aroma of wheat beer (WB A) was successfully simulated on the basis of 27 reference compounds in their natural concentrations using water/ethanol (95:5; v/v) as the matrix. PMID- 24219572 TI - Explaining the sociobiology of pyoverdin producing Pseudomonas: a comment on Zhang and Rainey (2013). AB - Over the past decade, there has been enormous interest in understanding the great diversity of microbial cooperative behaviors, including communication, group based swarming, fruiting-body formation, and the secretion of group-beneficial enzymes and food-scavenging molecules. Zhang and Rainey, henceforth Z&R, recently contended that sociomicrobiologists have been overzealous in their casting of microbes as inherently social organisms, and too hasty in interpreting microbial behaviors in a social evolutionary framework. This challenge accompanied a set of experiments in which they revisited one of the best-studied social behaviors in bacteria-the production of diffusible, sharable iron-scavenging siderophore molecules. Z&R posit that their findings challenge the view that siderophore production is a cooperative trait. Here, we demonstrate that their arguments are flawed, and stem from both technical mistakes and misunderstandings of social evolution theory. PMID- 24219574 TI - Individual differences in social dominance orientation predict support for the use of cognitive ability tests. AB - This study investigates the personality processes involved in the debate surrounding the use of cognitive ability tests in college admissions. In Study 1, 108 undergraduates (Mage = 18.88 years, 60 women, 80 Whites) completed measures of social dominance orientation (SDO), testing self-efficacy, and attitudes regarding the use of cognitive ability tests in college admissions; SAT/ACT scores were collected from the registrar. Sixty-seven undergraduates (Mage = 19.06 years, 39 women, 49 Whites) completed the same measures in Study 2, along with measures of endorsement of commonly presented arguments about test use. In Study 3, 321 American adults (Mage = 35.58 years, 180 women, 251 Whites) completed the same measures used in Study 2; half were provided with facts about race and validity issues surrounding cognitive ability tests. Individual differences in SDO significantly predicted support for the use of cognitive ability tests in all samples, after controlling for SAT/ACT scores and test self efficacy and also among participants who read facts about cognitive ability tests. Moreover, arguments for and against test use mediated this effect. The present study sheds new light on an old debate by demonstrating that individual differences in beliefs about hierarchy play a key role in attitudes toward cognitive ability test use. PMID- 24219573 TI - Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells. AB - Bitter taste receptors (TAS2Rs) have recently been found to be expressed on human airway smooth muscle (HASM), and their activation results in marked relaxation. These agents have been proposed as a new class of bronchodilators in the treatment of obstructive lung diseases because they act via a different mechanism than beta-agonists. The TAS2R signal transduction pathway in HASM has multiple elements that are potentially subject to regulation by inflammatory, genetic, and epigenetic mechanisms associated with asthma. To address this, expression, signaling, and physiologic functions of the three major TAS2Rs (subtypes 10, 14, and 31) on HASM were studied. Transcript expression of these TAS2Rs was not decreased in HASM cells derived from donors with asthma compared with those without asthma (n = 6 from each group). In addition, intracellular calcium ([Ca(2+)]i) signaling using TAS2R subtype-specific agonists (diphenhydramine, chloroquine, saccharin, and flufenamic acid) was not impaired in the cells derived from donors with asthma, nor was the response to quinine, which activates all three subtypes. HASM cell mechanics measured by magnetic twisting cytometry revealed equivalent TAS2R-mediated relaxation of methacholine-treated cells between the two groups. Human precision-cut lung slices treated with IL-13 caused a decrease in beta-agonist (formoterol)-mediated relaxation of carbachol contracted airways compared with control slices. In contrast, TAS2R-mediated relaxation was unaffected by IL-13. We conclude that TAS2R expression or function is unaffected in HASM cells derived from patients with asthma or the IL-13 inflammatory environment. PMID- 24219575 TI - A protocol for adult somatic cell nuclear transfer in medaka fish (Oryzias latipes) with a high rate of viable clone formation. AB - Previously, we successfully generated fully grown, cloned medaka (the Japanese rice fish, Oryzias latipes) using donor nuclei from primary culture cells of adult caudal fin tissue and nonenucleated recipient eggs that were heat shock treated to induce diploidization of the nuclei. However, the mechanism of clone formation using this method is unknown, and the rate of adult clone formation is not high enough for studies in basic and applied sciences. To gain insight into the mechanism and increase the success rate of this method of clone formation, we tested two distinct nuclear transfer protocols. In one protocol, the timing of transfer of donor nuclei was changed, and in the other, the size of the donor cells was changed; each protocol was based on our original methodology. Ultimately, we obtained an unexpectedly high rate of adult clone formation using the protocol that differed with respect to the timing of donor nuclei transfer. Specifically, 17% of the transplants that developed to the blastula stage ultimately developed into adult clones. The success rate with this method was 13 times higher than that obtained using the original method. Analyses focusing on the reasons for this high success rate of clone formation will help to elucidate the mechanism of clone formation that occurs with this method. PMID- 24219576 TI - A simplified approach for oocyte enucleation in mammalian cloning. AB - Despite its success in almost all farm and laboratory animals, somatic cell nuclear transfer (SCNT) is still a low-efficiency technique. In this investigation, we determined the impact of each enucleation step on oocyte viability (assessed by parthenogenetic activation): Hoechst (HO) staining, cytochalasin B, ultraviolet (UV) exposure, and demecolcine. Our data showed that of all the factors analyzed, UV exposure impaired oocyte development (cleavage, 59% for untreated oocytes vs. 8% UV exposed; blastocyst stage, 32% untreated vs. 0% UV exposed). A minor toxicity was detected following demecolcine treatment (cleavage, 62%; blastocyst stage, 13%). Next, we compared HO/UV (canonical) and demecolcine-assisted enucleation (DAE), with a straight removal of metaphase chromosomes without any chemical or physical aid (straight enucleation). DAE improved the preimplantation development of sheep cloned embryos compared to HO/UV enucleation (cleavage, 38% vs. 19%; blastocysts, 17% vs. 4%), yet straight enucleation resulted in the highest cleavage and blastocysts rates (61% and 30%, respectively). We concluded that: (1) UV exposure harms sheep oocyte and embryo development; (2) DAE may represent an alternative approach, especially for unskilled operators; and (3) straight enucleation remains, in our estimation, the most reliable and least harmful protocol for SCNT. PMID- 24219577 TI - Reprogramming of mouse cochlear cells by transcription factors to generate induced pluripotent stem cells. AB - As an initial step for using technology derived from induced pluripotent stem cells (iPSCs) in the field of inner ear therapeutics, we examined the potential of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, which are employed in the generation of iPSCs, for dedifferentiating cochlear epithelial cells. Otospheres, which are sphere-forming cells derived from dissociated cochlear epithelial cells of neonatal mice, were used as a cell source. The four transcription factors were introduced into otospheres using retroviral vectors. Virally transduced otospheres formed embryonic stem cell-like colonies that expressed markers for pluripotent stem cells and were capable of differentiating into the three germ layers in vivo and in vitro. These findings illustrate that viral transduction of four transcription factors can lead to reprogramming of cochlear epithelial cells, which may contribute to future studies of dedifferentiation of cochlear epithelial cells in tissue and identification of key molecules for otic induction. PMID- 24219578 TI - Induced pluripotent stem cell reprogramming by integration-free Sendai virus vectors from peripheral blood of patients with craniometaphyseal dysplasia. AB - Studies of rare genetic bone disorders are often limited due to unavailability of tissue specimens and the lack of animal models fully replicating phenotypic features. Craniometaphyseal dysplasia (CMD) is a rare monogenic disorder characterized by hyperostosis of craniofacial bones concurrent with abnormal shape of long bones. Mutations for autosomal dominant CMD have been identified in the ANK gene (ANKH). Here we describe a simple and efficient method to reprogram adherent cells cultured from peripheral blood to human induced pluripotent stem cells (hiPSCs) from eight CMD patients and five healthy controls. Peripheral blood mononuclear cells (PBMCs) were separated from 5-7 mL of whole blood by Ficoll gradient, expanded in the presence of cytokines and transduced with Sendai virus (SeV) vectors encoding OCT3/4, SOX2, KLF4, and c-MYC. SeV vector, a cytoplasmic RNA vector, is lost from host cells after propagation for 10-13 passages. These hiPSCs express stem cell markers, have normal karyotypes, and are capable of forming embryoid bodies in vitro as well as teratomas in vivo. Further differentiation of these patient-specific iPSCs into osteoblasts and osteoclasts can provide a useful tool to study the effects CMD mutations on bone, and this approach can be applied for disease modeling of other rare genetic musculoskeletal disorders. PMID- 24219579 TI - Does decreasing serum uric acid level prevent hypertension? - a nested RCT in cohort study: rationale, methods, and baseline characteristics of study cohort. AB - BACKGROUND: Previous epidemiologic studies have demonstrated an association between uric acid and hypertension. Our objective was to conduct a prospective cohort study with a nested randomised controlled trial (RCT in cohort) that aims to identify the association of hyperuricemia with the development of hypertension and to examine the efficacy of dietary intervention in lowering uric acid level and prevention of hypertension. METHODS/DESIGN: Participants were considered eligible to enrol for this cohort study if they were not diagnosed with hypertension until their last routine health examination. The characteristics of the eligible participants were analyzed. After enrolment, participants with prehypertension and hyperuricemia simultaneously were randomly distributed to either the intervention group or the control group. An education package of dietary intervention for lowering uric acid was delivered to the intervention group. The primary evaluation criterion was the first manifestation of hypertension. DISCUSSION: Based on the results of their health examination in 2010, 19, 724 subjects met the inclusion criteria and this source population guaranteed the required minimum sample size for this study. The baseline characteristics of the study cohort showed that hyperuricemia was associated with prehypertension, and was independent of age, body mass index (BMI), and abdominal obesity in females; however, in males it was contrary.The impact of lowering uric acid on the prevention of hypertension is still inconclusive. This RCT in cohort study provides important data on the prevention of hypertension, especially in patients with a high risk for hypertension development. Results are expected to be available in 2015. TRIAL REGISTRATION: The study is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-12002925). PMID- 24219580 TI - Serum vitamin D levels and VDR polymorphisms (BsmI and FokI) in patients and their household contacts susceptible to tuberculosis. AB - Vitamin D, an immunomodulator of macrophage function, can activate human antimycobacterial activity. Vitamin D deficiency (VDD) is associated with an impaired mycobacterial immunity and susceptibility to tuberculosis. It has been found that vitamin D and its receptor may be essential for immune function. In this study, we examined the serum 25(OH) vitamin D levels and its receptor (VDR) polymorphisms with susceptibility to tuberculosis in patients, household contacts and healthy controls. Serum 25(OH) vitamin D levels were measured in 75 cases (25 patients, 25 household contacts and 25 healthy controls), and polymorphisms (BsmI and FokI) were carried out in 335 cases (110 patients, 110 household contacts and 115 healthy controls). The proportion of serum 25(OH) vitamin D deficiency and insufficiency was high in patients (44, 58%) and household contacts (40, 48%) compared to controls (48%). The BB and Bb genotypes of BsmI were significantly associated in patients (P < 0.014; OR: 0.509; CI: 0.265-0.876) (P < 0.001; OR: 2.351; CI: 1.368-4.041) and household contacts (P < 0.04; OR: 0.575; CI: 0.336 0.985); (P < 0.002; OR: -2.267; CI: 1.32-3.895) when compared to healthy controls. The diplotype and MDR analysis showed the high-risk genotypes of BsmI and FokI polymorphisms. Vitamin D deficiency and its association with VDR gene polymorphisms may be useful to identify the high-risk group individuals. PMID- 24219581 TI - Trans and cis effects of axial fluoroalkyl ligands in vitamin B12 analogues: relationship between alkyl- and fluoroalkyl-cobalamins. AB - CF2HCbl, CF3Cbl , and CF3CH2Cbl have been synthesized and characterized in solution by (1)H NMR and UV-vis spectroscopy, and their X-ray crystal structures have been determined using synchrotron radiation. The structure of CF3CH2Cbl is reported for the first time, whereas those of CF2HCbl and CF3Cbl are re-examined to obtain more precise structural data. Comparison of the structural data obtained with the alkylcobalamin analogues, MeCbl and EtCbl, indicates that the Co-C and Co-NB3 bond lengths are shorter in the fluoroalkylcobalamins. The structural data of the fluoroalkylcobalamins previously reported in the literature had been conflicting in this regard. Thus, a much less dramatic shortening of the two axial bonds was found for CF3Cbl, whereas in the case of CF2HCbl, the Co-NB3 bond length is shorter than in MeCbl. Direct comparison of the structures of CF3CH2Cbl and EtCbl indicates a large distortion of the axial fragment in the former case that can be attributed to steric effects. A number of previously reported correlations of the effect of the beta-ligand on the structure and properties of cobalamins are re-examined in light of the present results. Particular emphasis is placed on the axial fragment. This analysis substantially confirms and, with the new data reported here, adjusts and expands the data set for correlations between trans and cis influences of the beta-ligand of cobalamins and their structure (Co-X and Co-NB3 distances and corrin fold angle) and properties (UV-vis spectra, NMR spectra, and pK(base-off)). PMID- 24219582 TI - Dynamics of Neotyphodium uncinatum and N-formylloline in Italian ryegrass, and their relation to insect resistance in the field. AB - AIMS: A fungal endophyte, Neotyphodium uncinatum, accumulates N-formylloline, which is toxic to Hemipteran insects, in Italian ryegrass. This study aimed to clarify the dynamics of N. uncinatum and N-formylloline in Italian ryegrass, and their relationship to insect resistance. METHODS AND RESULTS: Changes in the density and localization of N. uncinatum and N-formylloline in N. uncinatum infected Italian ryegrass were examined by real-time PCR and gas chromatography, respectively. Neotyphodium uncinatum multiplied on pseudostems at the flowering stage, and then increased on inflorescences at the ripening stage. On the other hand, N-formylloline accumulated heavily in inflorescences and leaf blades, but lightly in pseudostems at the ripening stage. In field experiments, N. uncinatum infected Italian ryegrass suppressed the occurrence of Stenotus rubrovittatus, which fed on the inflorescences, but was not effective to Laodelphax striatellus, which do not necessarily prefer a particular plant tissue. CONCLUSION: Localization of N. uncinatum and N-formylloline were discordant in Italian ryegrass. The N. uncinatum-infected Italian ryegrass was effective to only insects that prefer to feed on particular plant tissues containing N formylloline. SIGNIFICANCE AND IMPACT OF STUDY: Our data implies that the relationship between insect habits and the dynamics of alkaloids in plants is important for the effective use of endophyte-infected crops. PMID- 24219583 TI - Forensic entomologists: an evaluation of their status. AB - The National Academy of Sciences ( 2009 ) published a review charting several key recommendations on strengthening the forensic sciences as an entity as part of an initiative put forth by the USA Congress to streamline and improve the quality of the forensic sciences and their impact on the judiciary process. Although the review was not totally inclusive, many of its sentiments have permeated into all the forensic sciences. The following paper is designed to determine who is practicing the science of forensic entomology, and in what capacity, by questioning practicing forensic entomologists about the type of education obtained, their countries' standards and accreditation processes, as well as general demographic information such as age and gender. A 28-question survey was sent out to 300 forensic entomologists worldwide in 2009. Of the 70 respondents, 80% had a formal education (either Masters or PhD), and 66% published their research. Approximately 50% of respondents were involved in the delivery of expert evidence and writing up case reports, and countries were actively involved with accrediting personnel, facilities, and entomology kits. Many discrepancies within the reported practices and accreditation processes highlight the need for the adoption of a standard code of practice among forensic entomologists. PMID- 24219587 TI - When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis. AB - Supraspinal processes in humans can have a top-down enhancing effect on nociceptive processing in the brain and spinal cord. Studies have begun to suggest that such influences occur in conditions such as fibromyalgia (FM), but it is not clear whether this is unique to FM pain or common to other forms of chronic pain, such as that associated with osteoarthritis (OA). We assessed top down processes by measuring anticipation-evoked potentials and their estimated sources, just prior (< 500 ms) to laser heat pain stimulation, in 16 patients with FM, 16 patients with OA and 15 healthy participants, by using whole-brain statistical parametric mapping. Clinical pain and psychological coping factors (pain catastrophizing, anxiety, and depression) were well matched between the patient groups, such that these did not confound our comparisons between FM and OA patients. For the same level of heat pain, insula activity was significantly higher in FM patients than in the other two groups during anticipation, and correlated with the intensity and extent of reported clinical pain. However, the same anticipatory insula activity also correlated with OA pain, and with the number of tender points across the two patient groups, suggesting common central mechanisms of tenderness. Activation in the dorsolateral prefrontal cortex was reduced during anticipation in both patient groups, and was related to less effective psychological coping. Our findings suggest common neural correlates of pain and tenderness in FM and OA that are enhanced in FM but not unique to this condition. PMID- 24219588 TI - A long-life, high-rate lithium/sulfur cell: a multifaceted approach to enhancing cell performance. AB - Lithium/sulfur (Li/S) cells are receiving significant attention as an alternative power source for zero-emission vehicles and advanced electronic devices due to the very high theoretical specific capacity (1675 mA.h/g) of the sulfur cathode. However, the poor cycle life and rate capability have remained a grand challenge, preventing the practical application of this attractive technology. Here, we report that a Li/S cell employing a cetyltrimethyl ammonium bromide (CTAB) modified sulfur-graphene oxide (S-GO) nanocomposite cathode can be discharged at rates as high as 6C (1C = 1.675 A/g of sulfur) and charged at rates as high as 3C while still maintaining high specific capacity (~ 800 mA.h/g of sulfur at 6C), with a long cycle life exceeding 1500 cycles and an extremely low decay rate (0.039% per cycle), perhaps the best performance demonstrated so far for a Li/S cell. The initial estimated cell-level specific energy of our cell was ~ 500 W.h/kg, which is much higher than that of current Li-ion cells (~ 200 W.h/kg). Even after 1500 cycles, we demonstrate a very high specific capacity (~ 740 mA.h/g of sulfur), which corresponds to ~ 414 mA.h/g of electrode: still higher than state-of-the-art Li-ion cells. Moreover, these Li/S cells with lithium metal electrodes can be cycled with an excellent Coulombic efficiency of 96.3% after 1500 cycles, which was enabled by our new formulation of the ionic liquid-based electrolyte. The performance we demonstrate herein suggests that Li/S cells may already be suitable for high-power applications such as power tools. Li/S cells may now provide a substantial opportunity for the development of zero-emission vehicles with a driving range similar to that of gasoline vehicles. PMID- 24219589 TI - High presence/absence gene variability in defense-related gene clusters of Cucumis melo. AB - BACKGROUND: Changes in the copy number of DNA sequences are one of the main mechanisms generating genome variability in eukaryotes. These changes are often related to phenotypic effects such as genetic disorders or novel pathogen resistance. The increasing availability of genome sequences through the application of next-generation massive sequencing technologies has allowed the study of genomic polymorphisms at both the interspecific and intraspecific levels, thus helping to understand how species adapt to changing environments through genome variability. RESULTS: Data on gene presence/absence variation (PAV) in melon was obtained by resequencing a cultivated accession and an old relative melon variety, and using previously obtained resequencing data from three other melon cultivars, among them DHL92, on which the current draft melon genome sequence is based. A total of 1,697 PAV events were detected, involving 4.4% of the predicted melon gene complement. In all, an average 1.5% of genes were absent from each analyzed cultivar as compared to the DHL92 reference genome. The most populated functional category among the 304 PAV genes of known function was that of stress response proteins (30% of all classified PAVs). Our results suggest that genes from multi-copy families are five times more likely to be affected by PAV than singleton genes. Also, the chance of genes present in the genome in tandem arrays being affected by PAV is double that of isolated genes, with PAV genes tending to be in longer clusters. The highest concentration of PAV events detected in the melon genome was found in a 1.1 Mb region of linkage group V, which also shows the highest density of melon stress-response genes. In particular, this region contains the longest continuous gene-containing PAV sequence so far identified in melon. CONCLUSIONS: The first genome-wide report of PAV variation among several melon cultivars is presented here. Multi-copy and clustered genes, especially those with putative stress-response functions, were found to be particularly affected by PAV polymorphisms. As cucurbits are known to possess a significantly lower number of defense-related genes compared to other plant species, PAV variation may play an important role in generating new pathogen resistances at the subspecies level. In addition, these results show the limitations of single reference genome sequences as the only basis for characterization and cloning of resistance genes. PMID- 24219590 TI - The role of pain catastrophizing in experimental pain perception. AB - BACKGROUND: Pain is a subjective experience influenced by multiple factors, and tremendous variety within individuals is present. To evaluate emotional state of pain, catastrophizing score can be used. This study investigated pain catastrophizing ratings in association with experimental pain perception. METHOD: Experimental pain was induced using thermal heat and cold stimulation of skin, mechanical stimulation of muscle and bone, and thermal, mechanical, and electrical stimulation of the gastrointestinal tract in healthy participants (N = 41). Prior to experimental sessions, a pain catastrophizing questionnaire was filled out by each participant. RESULTS: Based on the median catastophizing score, participants were divided into two groups: noncatastrophizers and low catastrophizers. No significant difference was found between low-catastrophizers and noncatastrophizers in thermal heat stimulation of skin, mechanical stimulation of muscle and bone, and rectal electrical stimulation (All P > 0.05). Low-catastrophizers were more sensitive to visceral thermal stimulation (4.7%, P = 0.02) and visceral mechanical stimulation (29.7%, P = 0.03). For participants that completed the 120 seconds ice water stimulation, noncatastrophizers reported 13.8% less pain than low-catastrophizers (P = 0.02). A positive correlation between PCS score and pain perception on cold pressor test was found (r = 0.4, P = 0.02). By extrapolating data, further analysis of the total group was performed and no differences (both P > 0.05) were observed. CONCLUSION: Even small increments in pain catastrophizing score can influence pain perception to deep and tonic stimulations. Catatrophizing may partly explain the variability found in experimental pain studies. PMID- 24219591 TI - Ultrasmooth, highly spherical monocrystalline gold particles for precision plasmonics. AB - Ultrasmooth, highly spherical monocrystalline gold particles were prepared by a cyclic process of slow growth followed by slow chemical etching, which selectively removes edges and vertices. The etching process effectively makes the surface tension isotropic, so that spheres are favored under quasi-static conditions. It is scalable up to particle sizes of 200 nm or more. The resulting spherical crystals display uniform scattering spectra and consistent optical coupling at small separations, even showing Fano-like resonances in small clusters. The high monodispersity of the particles we demonstrate should facilitate the self-assembly of nanoparticle clusters with uniform optical resonances, which could in turn be used to fabricate optical metafluids. Narrow size distributions are required to control not only the spectral features but also the morphology and yield of clusters in certain assembly schemes. PMID- 24219592 TI - Theoretical study of binding and permeation of ether-based polymers through interfaces. AB - We present a molecular dynamics simulation study on the interactions of poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and their ABA-type block copolymer, poloxamers, at water/n-heptane and 1,2-dimyristoyl-sn-glycero-3 phospatidycholine (DMPC) lipid bilayer/water interfaces. The partition coefficients in water/1-octanol of the linear polyethers up to three monomers were calculated. The partition coefficients evidenced a higher hydrophobicity of the PPO in comparison to PEO. At the water/n-heptane interface, the polymers tend to adopt elongated conformations in agreement with similar experimental ellipsometry studies of different poloxamers. In the case of the poloxamers at the n-heptane/water interface, the stronger preference of the PPO block for the hydrophobic phase resulted in bottle-brush-type polymer conformations. At lipid bilayer/water interface, the PEO polymers, as expected from their hydrophilic nature, are weakly adsorbed on the surface of the lipid bilayer and locate in the water phase close to the headgroups. The free energy barriers of permeation calculated for short polymer chains suggest a thermodynamics propensity for the water phase that increase with the chain length. The lower affinity of PEO for the hydrophobic interior of the lipid bilayer resulted in the spontaneous expulsion within the simulation time. On the contrary, PPO chains and poloxamers have a longer residence time inside the bilayer, and they tend to concentrate in the tail region of the bilayer near the polar headgroups. In addition, polymers with PPO unit length comparable to the thickness of the hydrophobic region of the bilayer tend to span across the bilayer. PMID- 24219593 TI - Allometric constraints and the evolution of allometry. AB - Morphological traits often covary within and among species according to simple power laws referred to as allometry. Such allometric relationships may result from common growth regulation, and this has given rise to the hypothesis that allometric exponents may have low evolvability and constrain trait evolution. We formalize hypotheses for how allometry may constrain morphological trait evolution across taxa, and test these using more than 300 empirical estimates of static (within-species) allometric relations of animal morphological traits. Although we find evidence for evolutionary changes in allometric parameters on million-year, cross-species time scales, there is limited evidence for microevolutionary changes in allometric slopes. Accordingly, we find that static allometries often predict evolutionary allometries on the subspecies level, but less so across species. Although there is a large body of work on allometry in a broad sense that includes all kinds of morphological trait-size relationships, we found relatively little information about the evolution of allometry in the narrow sense of a power relationship. Despite the many claims of microevolutionary changes of static allometries in the literature, hardly any of these apply to narrow-sense allometry, and we argue that the hypothesis of strongly constrained static allometric slopes remains viable. PMID- 24219594 TI - An untimely death: Dr Anne Szarewski (1 September 1959-24 August 2013). PMID- 24219595 TI - Contraceptive use and method among immigrant women in France: relationship with socioeconomic status. AB - OBJECTIVES: We investigated the relationship between socioeconomic status and the use and method of contraception among immigrant, second-generation immigrant, and non-immigrant women in France. METHODS: We analysed data from the 2008-2009 survey 'Trajectories and origins: Survey on the diversity of populations in France'. A total of 7070 women aged 18 to 45 years were identified, and information concerning contraceptive use and choice was obtained by self-report. Polytomous logistic regression models were used to assess association estimates. RESULTS: Recent contraceptive use among immigrant and second-generation immigrant women was significantly lower than that of non-immigrant women. Lower educational attainment and unemployment were associated with an estimated 31~59% reduction in odds of contraceptive use for immigrant and second-generation immigrant women; however, this was not the case for non-immigrant women. Among the latter, lower educational attainment appeared to be associated with increased use of oral contraceptives. CONCLUSIONS: Our findings suggest the need to advance our understanding of potential barriers to contraceptives created by socioeconomic forces across different societal/cultural contexts. PMID- 24219596 TI - Scientific research of senior Italian academics of occupational medicine: a citation analysis of products published during the decade 2001-2010. AB - This article analyzes 10 years of scientific publications among senior Italian academics in occupational medicine by means of citation analysis. Articles published during the decade 2001-2010 were analyzed by means of Elsevier's Scopus. Scientific performance was assessed by means of 9 different indices (including total number of papers, total citations, h-index). Most papers were submitted to journals of allergy and respiratory medicine, biochemistry, and toxicology. Only 11.9% of the 1,689 papers were published in journals of occupational medicine. The authors' h-index was 10.1 (mean) and 9.5 (median) for the overall production. Productivity was associated with number of contributing authors. Most papers cover topics in the mainstream of other disciplines, evidencing that journals of occupational medicine do not play a primary role in the scientific panorama of medical sciences. This could imply consequences for the discipline. PMID- 24219598 TI - Cytokeratin-19 as a biomarker in urine and in serum for the diagnosis of endometriosis--a prospective study. AB - Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability. Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis. A noninvasive, rapid diagnostic test is urgently needed. In this prospective study, we evaluated the usefulness of Cytokeratin-19 (CK19) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA. 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence (n = 44) or absence (n = 32) of endometriosis. There was no statistically significant correlation between the concentration of CK19 in urine (p = 0.51) or in serum (p = 0.77) and the diagnosis of endometriosis. Assigning the samples to the proliferative or secretory cycle stage did not sufficiently lower the p values. In this study, the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size. Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis. PMID- 24219599 TI - The immune system and aging: a review. AB - Abstract The concept of immunosenescence reflects age-related changes in immune responses, both cellular and serological, affecting the process of generating specific responses to foreign and self-antigens. The decline of the immune system with age is reflected in the increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, autoimmune and other chronic diseases. Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be more affected by the age-related changes in the immune system. Additionally, aged individuals tend to present a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis and diabetes). However, some individuals arrive to advanced ages without any major health problems, referred to as healthy aging. The immune system dysfunction seems to be somehow mitigated in this population, probably due to genetic and environmental factors yet to be described. In this review, an attempt is made to summarize the current knowledge on how the immune system is affected by the aging process. PMID- 24219600 TI - The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms. AB - BACKGROUND: Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. RESULTS: In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33-36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. CONCLUSIONS: The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles are broken down and cleared. This is an important finding, as it shows that the nanoparticles can be safely used as a vaccine platform without the risk of prolonged side effects. Furthermore, it demonstrates that technetium carbonyl radiolabeling of our protein-based nanoparticles can be used to evaluate their pharmacokinetic properties in vivo. PMID- 24219601 TI - Effects of rootstock/scion combinations on the flavor of citrus fruit. AB - We examined sensory quality, total soluble solids (TSS) and acidity levels, and aroma volatiles compositions of 'Or' and 'Odem' mandarins grafted on sour orange (SO), Volkamer lemon (Volka), and US-812 rootstocks; 'Valencia' oranges grafted on SO, Volka, and *639 rootstocks; and a new pummelo * grapefruit hybrid cv. 'Redson' grafted on SO, Volka, and macrophylla rootstocks. TSS and acidity levels of all species were lower in juice of fruits on Volka than on SO. Sensory quality evaluations revealed that 'Odem' mandarins and 'Redson' fruits grown on SO were preferred to those on Volka but the rootstocks had no notable effects on flavor perception of 'Or' mandarins and 'Valencia' oranges. Chromatographic analysis revealed that contents of aroma volatiles, especially terpenes, in homogenized segments of 'Odem' and 'Redson' but not of 'Or' and 'Valencia' were significantly lower on Volka than on SO. Overall, the effects of rootstocks on citrus fruit flavor depended on specific rootstock/scion interactions. Furthermore, the flavor of some varieties grown on Volka was inferior to that on SO because of lower TSS and acidity levels and lower aroma volatiles contents. PMID- 24219602 TI - Within-person distributions of neuropsychological test scores as a function of dementia severity. AB - OBJECTIVE: The distribution of a person's scores on a battery of neuropsychological tests reflects the nature and extent of intraindividual variability and may provide clinically useful information not captured by examining test scores in isolation. We sought to test the hypothesis that systematic alterations of within-person test-score distributions characterize worsening cognitive impairment. METHOD: We analyzed cross-sectional data from 2 datasets that included 395 clinical patients and 135 neurologically normal older adults (>=60 years old). We computed each person's mean, standard deviation, skewness, and kurtosis for a battery of 13 neuropsychological measures and compared these distributional properties across groups. RESULTS: Most healthy older adults produced normal (Gaussian) test-score distributions. Among patients, test-score distributions increasingly shifted away from normal with worsening cognitive impairment. Worsening dementia was accompanied by progressively lower mean scores and increasingly positive skew. Within-person standard deviations initially grew at mild levels of impairment, but then shrank with worsening dementia, resulting in positive kurtosis. CONCLUSIONS: Within-person distributional properties vary as a function of dementia severity. Despite the limitations associated with using a clinical rather than a research sample, the analyses reported here serve as a "proof of concept" and suggest that similar investigations with more rigorously characterized patient samples may be fruitful. PMID- 24219603 TI - Enhanced decision making and risk avoidance in high-functioning autism spectrum disorder. AB - OBJECTIVE: Everyday decision making requires integration of a broad range of information from a variety of sources, including cognitive and emotional processes. For individuals with autism spectrum disorder (ASD), everyday decision making can be difficult. The mechanisms that underlie decision making in young people diagnosed with ASD have not been fully explored. METHOD: We studied children and young adolescents with autism spectrum disorder (ASD; n = 48) compared with an age- and ability-matched typical control group (CON; n = 54). We evaluated performance and psycho-physiological responsivity during the Iowa Gambling Task (IGT), an affective decision-making task. RESULTS: ASD participants were superior to control participants on overall performance (p < .05), especially because of significantly better learning in later stages of the task. While both groups showed robust and equal psycho-physiological arousal to disadvantageous decks, the groups differed in their choice of card type, with the CON group choosing more often from the frequent-gain disadvantageous deck, despite occasional large losses; while the ASD group chose prominently from the advantageous decks. CONCLUSIONS: A decision-making style characterized by a drive to avoid potential loss rather than to seek possible reward may help decision making for ASD in some situations, but ultimately hinder functioning in relation to prosocial engagement and other complex situations where gain rather than punishment is the most effective motivating factor. PMID- 24219604 TI - The genesis of closing-in in Alzheimer disease and vascular dementia: a comparative clinical and experimental study. AB - OBJECTIVE: Closing-in (CI) in visuo-constructional tasks occurs when a drawing is reproduced close to or superimposed on the original model. CI has been often observed in Alzheimer disease (AD) patients and only rarely investigated in patients with vascular dementia (VD). Recent studies suggested that CI in AD patients represents a default behavior released by frontal-executive impairments, but the cognitive mechanisms behind this phenomenon in VD patients have not been clarified. We aimed to ascertain whether the same mechanisms could determine CI in VD and in AD patients. For this purpose we explored whether CI is related to frontal-executive or visuospatial impairments in a prospective sample of AD and VD patients, and investigated whether CI can be induced by a secondary task in patients with either disease. METHOD: Sixty-three VD patients and 70 AD patients underwent a neuropsychological assessment of frontal-executive and visuospatial skills, and a copying drawings task for CI. Moreover, VD and AD patients without CI also performed a drawing copying task combined with a simple or a demanding verbal task. RESULTS: In both VD and AD patients CI was related to frontal executive impairments, with more severe forms of CI related to greater frontal executive defects. In AD patients the tendency to deviate toward a salient model was significantly enhanced by reduction of cognitive resources, whereas VD could compensate for this tendency. CONCLUSIONS: CI is related to the tendency to deviate toward a salient model and can be released by frontal-executive impairments in demented patients, independently from clinical diagnosis. PMID- 24219605 TI - I find my way in a maze but not in my own territory! Navigational processing in developmental topographical disorientation. AB - OBJECTIVE: Developmental Topographical Disorientation (DTD) is a selective difficulty in way-finding showed by individuals with normal intellectual ability. We aimed to clarify whether getting lost even in familiar contexts could be because of a variety of developmental deficits that may affect the acquisition of one or more navigational competencies. METHOD: Two DTD individuals were submitted to neuropsychological assessment and MRI exam, to verify the absence of further cognitive deficits and brain abnormalities; navigational and visuospatial tasks, and Radial Arm Maze (RAM) paradigms to assess spatial competencies; and switching paradigms to assess backward inhibition processes in spatial- and no-spatial contexts. DTD performances were compared with those of controls matched for gender, age, and education. RESULTS: DTD participants were not able to retrace a previously showed route, but they could recognize previously seen landmarks. They performed RAM paradigms without significant differences from controls and adopted complex navigational strategies as the cognitive mapping. It is interesting that DTD participants exhibited a peculiar alteration of Backward Inhibition, a mechanism that allows flexibly adapting to continuously changing environments. CONCLUSIONS: These findings demonstrate that getting lost for DTD participants did not imply the lack of basic navigational strategies and was not related to visuospatial or spatial memory deficits. We discuss the hypothesis that Backward Inhibition might play a role in updating environment representation during navigation. PMID- 24219606 TI - Clinical and psychological characteristics of the initial cohort of the Dominantly Inherited Alzheimer Network (DIAN). AB - OBJECTIVE: The purpose was to describe clinical, cognitive, and personality characteristics at baseline assessment of 249 participants, 19 to 60 years of age, in a multinational longitudinal study of autosomal dominant Alzheimer's disease (ADAD). METHOD: Participants (74% cognitively normal) were from ADAD families with mutations in 1 of 3 genes (APP, PSEN1, or PSEN2). Mixed model analyses, including family as a random variable and controlling for years from expected time of symptomatic onset of ADAD based on parental age at onset, compared 3 groups (cognitively normal mutation noncarriers, cognitively normal mutation carriers, very mildly impaired mutation carriers). RESULTS: Global cognitive deficits similar to those observed in late-life sporadic Alzheimer's disease (AD) existed in very mild ADAD compared with cognitively normal carriers and noncarriers on all but 2 measures (Digit Span Backward, Letter Fluency for FAS) of episodic memory, semantic memory, working memory, attention, and speeded visuospatial abilities. Demented individuals were less extraverted, open, and conscientious than cognitively normal participants on the International Personality Item Pool. Differences in the relation between 3 measures (Logical Memory, Digit Symbol, attention switching) and time to expected age at symptomatic onset indicate that cognitive deficits on some measures can be detected in mutation carriers prior to symptomatic AD, and hence should be useful markers in subsequent longitudinal follow-up. CONCLUSIONS: Overall cognitive and personality deficits in very mild ADAD are similar to those seen in sporadic AD. Cognitive deficits also occur in asymptomatic mutation carriers who are closer to the expected time of dementia onset. PMID- 24219607 TI - Plugging the attention deficit: perceptual load counters increased distraction in ADHD. AB - OBJECTIVE: Increased vulnerability to extraneous distraction is a key symptom of Attention-Deficit Hyperactivity Disorder (ADHD), which may have particularly disruptive consequences. Here we apply Load Theory of attention to increase understanding of this symptom, and to explore a potential method for ameliorating it. Previous research in nonclinical populations has highlighted increased perceptual load as a means of improving the ability to focus attention and avoid distraction. The present study examines whether adults with ADHD can also benefit from conditions of high perceptual load to improve their focused attention abilities. METHOD: We tested adults with ADHD and age- and IQ-matched controls on a novel measure of irrelevant distraction under load, designed to parallel the form of distraction that is symptomatic of ADHD. During a letter search task, in which perceptual load was varied through search set size, participants were required to ignore salient yet entirely irrelevant distractors (colorful images of cartoon characters) presented infrequently (10% of trials). RESULTS: The presence of these distractors produced a significantly greater interference effect on the search RTs for the adults with ADHD compared with controls, p = .005, etap2 = .231. Perceptual load, however, significantly reduced distractor interference for the ADHD group and was as effective in reducing the elevated distractor interference in ADHD as it was for controls. CONCLUSIONS: These findings clarify the nature of the attention deficit underlying increased distraction in ADHD, and demonstrate a tangible method for overcoming it. PMID- 24219608 TI - The NIH Toolbox Cognition Battery: results from a large normative developmental sample (PING). AB - OBJECTIVE: The NIH Toolbox Cognition Battery (NTCB) was designed to provide a brief, efficient computerized test of key neuropsychological functions appropriate for use in children as young as 3 years of age. This report describes the performance of a large group of typically developing children and adolescents and examines the impact of age and sociocultural variables on test performance. METHOD: The NTCB was administered to a sample of 1,020 typically developing males and females ranging in age from 3 to 20 years, diverse in terms of socioeconomic status (SES) and race/ethnicity, as part of the new publicly accessible Pediatric Imaging, Neurocognition, and Genetics (PING) data resource, at 9 sites across the United States. RESULTS: General additive models of nonlinear age-functions were estimated from age-differences in test performance on the 8 NTCB subtests while controlling for family SES and genetic ancestry factors (GAFs). Age accounted for the majority of the variance across all NTCB scores, with additional significant contributions of gender on some measures, and of SES and race/ethnicity (GAFs) on all. After adjusting for age and gender, SES and GAFs explained a substantial proportion of the remaining unexplained variance in Picture Vocabulary scores. CONCLUSIONS: The results highlight the sensitivity to developmental effects and efficiency of this new computerized assessment battery for neurodevelopmental research. Limitations are observed in the form of some ceiling effects in older children, some floor effects, particularly on executive function tests in the youngest participants, and evidence for variable measurement sensitivity to cultural/socioeconomic factors. PMID- 24219609 TI - The lost ability to find the way: topographical disorientation after a left brain lesion. AB - OBJECTIVE: We report the case of a patient (M.S.) who, after a left brain damage in posteromedial areas, showed a deficit in determining the direction of any destination with respect to his current position or to external frames (heading disorientation). Given that spatial cognition includes a wide range of cooperating abilities, we deemed that M.S.'s spatial disorientation could be ascribed to specific alterations within this multicomponent system where landmarks and spatial frames of reference contribute to organize information for different purposes. METHOD: M.S. and 12 healthy elderly people (NCs) were submitted to an extensive neuropsychological assessment and to 2 ad hoc spatial tasks: (a) Object-Location Memory Task (what, where, and their binding); and (b) spatial memory task combining categorical (nonmetric)/coordinate (metric) relations with egocentric/allocentric frames of reference (in verbal and visuomotor conditions). RESULTS: M.S.'s performance was compared with that of NCs by means of a modified t test to small control sample size. M.S. met difficulty in positional processing and binding but not in object recognition. M.S. showed a selective deficit in the coordinate component in verbal (combined with both egocentric and allocentric frames) and visuomotor (only with the egocentric frame) spatial judgment tasks. In contrast, the categorical component looked always preserved in both frames of reference. CONCLUSIONS: The left posteromedial brain areas contribute in combining and translating metric relations according to frames of reference and in using these representations to guide actions according to an egocentric perspective. PMID- 24219611 TI - The neuropsychological outcomes of concussion: a systematic review of meta analyses on the cognitive sequelae of mild traumatic brain injury. AB - Mild Traumatic Brain Injury (mTBI), also known as concussion, has become a growing public health concern, prevalent in both athletic and military settings. Many researchers have examined post-mTBI neuropsychological outcomes, leading to multiple meta-analyses amalgamating individual study results. OBJECTIVE: Considering the plethora of meta-analytic findings, the next logical step stands as a systematic review of meta-analyses, effectively reporting key moderators that predict post-mTBI neuropsychological outcomes. METHOD: A systematic review of reviews yielded 11 meta-analyses meeting inclusion criteria (i.e., English language systematic reviews/meta-analyses covering post-mTBI observational cognitive research on late adolescents/adults), with their findings qualitatively synthesized based on moderator variables (i.e., cognitive domain, time since injury, past head injury, participant characteristics, comparison group, assessment technique, and persistent symptoms). RESULTS: The overall effect sizes ranged for both general (range: .07-.61) and sports-related mTBI (range: .40-.81) and differed both between and within cognitive domains, with executive functions appearing most sensitive to multiple mTBI. Cognitive domains varied in recovery rates, but overall recovery occurred by 90 days postinjury for most individuals and by 7 days postinjury for athletes. Greater age/education and male gender produced smaller effects sizes, and high school athletes suffered the largest deficits post-mTBI. Control-group comparisons yielded larger effects than within person designs, and assessment techniques had limited moderating effects. CONCLUSIONS: Overall, meta-analytic review quality remained low with few studies assessing publication or study quality bias. Meta-analyses consistently identified adverse acute mTBI-related effects and fairly rapid symptom resolution. Future meta-analyses should better operationally define cognitive constructs to produce more consistent effect estimates across domains. PMID- 24219610 TI - Memory consolidation in aging and MCI after 1 week. AB - OBJECTIVE: To assess consolidation in amnestic mild cognitive impairment (aMCI), controlling for differences in initial learning and using a protracted delay period for recall. METHOD: 15 individuals with aMCI were compared with 15 healthy older adult controls on a story learning task. Subjects were trained to criteria to equalize initial learning across subjects. Recall was tested at both the 30 min typically used delay and a 1-week delay used to target consolidation. RESULTS: Using repeated measures ANOVAs adjusted for age, we found group * time point interactions across the entire task between the final trial and 30-min delay, and again between the 30-min and 1-week delay periods, with aMCI having greater declines in recall as compared with controls. Significant group main effects were also found, with aMCI recalling less than controls. CONCLUSION: Consolidation was impaired in aMCI as compared with controls. Our findings indicate that aMCI-related performance typically measured at 30 min underestimates aMCI-associated memory deficits. This is the first study to isolate consolidation by controlling for initial learning differences and using a protracted delay period to target consolidation in an aMCI sample. PMID- 24219612 TI - Executive functions in cocaine-dependent patients with Cluster B and Cluster C personality disorders. AB - OBJECTIVE: Cocaine dependence often co-occurs with personality disorders from Clusters B and C, which are inherently associated with some of the executive dysfunctions found in addiction. We address the question of whether the comorbidity between cocaine dependence and different types of personality disorders is associated with differential profiles of executive deficits compatible with their personality dysfunction. We predicted that the comorbidity with Cluster B disorders would be associated with inhibition and shifting deficits, whereas the comorbidity with Cluster C disorders would be associated with working memory deficits. METHOD: We tested 107 participants (22 cocaine users with Cluster B disorders, 15 cocaine users with Cluster C disorders, 36 cocaine users without comorbidities, and 34 controls) using tests of working memory, attention, inhibition, and shifting. Groups were statistically matched on IQ and had no Axis I comorbidities (other than substance-related). Based on the performance of the control group, we obtained z-score composite measures of working memory, attention/inhibition, shifting, and global executive impairment. We tested group differences in these composite measures using univariate analyses of variance and Sidak tests corrected for multiple comparisons. RESULTS: Cocaine users with Cluster B disorders had poorer attention/inhibition, whereas cocaine users with comorbid Cluster C disorders had poorer working memory. Cluster B and noncomorbid cocaine users (but not Cluster C users) differed from controls on the global executive impairment measure. CONCLUSION: The comorbidity between cocaine dependence and personality disorders from Clusters B and C is associated with executive function deficits that are compatible with their respective personality dysfunctions. PMID- 24219613 TI - Verbal prompting to improve everyday cognition in MCI and unimpaired older adults. AB - OBJECTIVE: This study investigated the effect of verbal prompting on elders' 10 year longitudinal change in everyday cognition. Differential effects of prompting associated with impaired cognitive status were also examined. METHOD: At baseline, 2,802 participants (mean age = 73.6 years, mean education = 13.5 years) from the Advanced Cognitive Training for Independent and Vital Elderly trial were classified as unimpaired, having amnestic mild cognitive impairment (MCI) or nonamnestic MCI, based on psychometric algorithm. Participants were given the Observed Tasks of Daily Living (OTDL; a behavioral measure with tasks involving medication management/finances/telephone use) at baseline and at 1-, 2-, 3-, 5-, and 10-year follow-ups. When participants said "I don't know" or did not respond to an item, they received a standardized verbal prompt. At each occasion, unprompted (sum of items correct without prompting) and prompted (sum of items correct including both prompted and unprompted) scores were derived for each participant. Multilevel modeling, adjusting for demographics/health/training group, was used to determine the trajectories of OTDL performance. RESULTS: Persons with MCI performed at lower levels than those who were unimpaired (amnestic < nonamnestic < unimpaired), and for all groups, prompted performance exceeded unprompted in all years. There was differential performance of the prompting conditions over time; prompted performance, unlike unprompted, was relatively protected from age-related decline, and persons with MCI experienced greater improvement due to prompting. CONCLUSIONS: Very simple prompting appears to enhance and maintain performance on a task of everyday cognition over 10 years for both unimpaired and mildly impaired older adults. PMID- 24219614 TI - Neural correlates of prospective memory in individuals with schizotypal personality features. AB - OBJECTIVE: Prospective memory (PM) refers to the ability to remember to perform actions in the future. Schizophrenia spectrum disorders show impairments in PM but neural correlates of these impairments remain unclear. The present study aimed to examine brain activation during PM to identify impairments in individuals with schizotypal personality features. METHOD: Nineteen participants with schizotypal features and 22 healthy controls participated in a functional MRI experiment while performing a PM task. RESULTS: Results showed that the prefrontal cortex (including Brodmann Area [BA] 10), middle temporal gyrus, and precuneus were activated when performing the PM task compared with baseline. The schizotypal and control groups did not differ in behavioral PM performance. However, participants with schizotypal features showed decreased activations in the inferior and medial frontal lobes (BA 45, and 8). CONCLUSIONS: These results confirmed that the PM network involves prefrontal cortex, including BA 10. The lower activation in prefrontal cortex of individuals with schizotypal features when performing a PM task indicates brain activation abnormality. Notably, this abnormality may occur in the absence of any behavioral manifestation. Our findings support the hypothesis of frontal lobe involvement in PM deficits observed in individuals with schizotypal features. PMID- 24219615 TI - Functional implications of regulatory B cells in human IgA nephropathy. AB - IgA nephropathy (IgAN) diagnosis remains largely based upon immunohistologic detection of IgA- and IgG-containing glomerular deposits in renal mesangial cells, and little is known about the underlying pathogenic mechanisms. This study examines the putative contribution of B cell types, including the Breg type, to IgAN pathogenesis. Twenty-four patients with IgAN and proteinuria (Group A: <3.5 g/24 h, n = 13; Group B: >3.5 g/24 h, n = 11) and 10 healthy controls were enrolled. The frequencies of B cell subtypes in venous blood were measured by flow cytometry. Galactose-deficient IgA1 was measurement by ELISA. Needle biopsies were analysed by histology and immunofluorescence microscopy. Correlation between clinical features and B cell subtypes, including the regulatory B (Breg) cells, and Breg cell-derived immunomodulatory cytokine IL-10 was assessed by Spearman's rank correlation test. IgAN patients had significantly higher frequencies of CD27(+) CD19(+) , CD38(+) CD19(+) , CD86(+) CD19(+) and CD5(+) CD19(+) B cells than the healthy controls, but significantly lower levels of Breg cells and intracellular expression of IL-10 protein in the Breg subtype. Serum IgA concentration positively correlated with CD27(+) CD19(+) B cell frequency and negatively correlated with IL-10(+) Breg cell frequency in IgAN patients, and the percentage of CD19(+) CD5(+) CD1d(+) in CD19(+) cells was negatively correlated with the level of serum Gd-IgA1. Furthermore, the frequencies of CD19(+) CD38(+) and CD19(+) CD86(+) in the CD19(+) subpopulation negatively correlated with the estimated glomerular filtration rate of IgAN patients. Several of the CD19(+) B cell subtypes and the IL-10(+) Breg cells are differentially expressed in IgAN patients and may contribute to the disease pathogenesis. PMID- 24219616 TI - Conditional Dicer substrate formation via shape and sequence transduction with small conditional RNAs. AB - RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) enables knockdown of a gene of choice, executing the logical operation: silence gene Y. The fact that the siRNA is constitutively active is a significant limitation, making it difficult to confine knockdown to a specific locus and time. To achieve spatiotemporal control over silencing, we seek to engineer small conditional RNAs (scRNAs) that mediate 'conditional RNAi' corresponding to the logical operation: if gene X is transcribed, silence independent gene Y. By appropriately selecting gene X, knockdown of gene Y could then be restricted in a tissue- and time specific manner. To implement the logic of conditional RNAi, our approach is to engineer scRNAs that, upon binding to mRNA 'detection target' X, perform shape and sequence transduction to form a Dicer substrate targeting independent mRNA 'silencing target' Y, with subsequent Dicer processing yielding an siRNA targeting mRNA Y for destruction. Toward this end, here we design and experimentally validate diverse scRNA mechanisms for conditional Dicer substrate formation. Test tube studies demonstrate strong OFF/ON conditional response, with at least an order of magnitude increase in Dicer substrate production in the presence of the cognate mRNA detection target. By appropriately dimensioning and/or chemically modifying the scRNAs, only the product of signal transduction, and not the reactants or intermediates, is efficiently processed by Dicer, yielding siRNAs. These mechanism studies explore diverse design principles for engineering scRNA signal transduction cascades including reactant stability vs metastability, catalytic vs noncatalytic transduction, pre- vs post transcriptional transduction, reactant and product molecularity, and modes of molecular self-assembly and disassembly. PMID- 24219617 TI - In vitro metabolic profile and in vivo antischistosomal activity studies of (eta(6)-praziquantel)Cr(CO)3 derivatives. AB - In vitro metabolic behavior was investigated for two chromium tricarbonyl derivatives of the antischistosomal drug praziquantel (PZQ) with the formula (eta(6)-PZQ)Cr(CO)3 (1 and 2), by use of human liver microsomes. The metabolic profiles of the derivatives differ significantly. The optically pure (eta(6) PZQ)Cr(CO)3 derivatives (S, Sp)-1, (R, Rp)-1, (S, Rp)-2, and (R, Sp)-2 were also prepared to assess the eudysmic ratios of 1 and 2 against Schistosoma mansoni in vitro. A strong enantioselective antischistosomal activity was observed. The R enantiomers are highly active against adult schistosomes in vitro (IC50 0.08-0.13 MUM), whereas both S-enantiomers lack activity. The in vivo activity of 1 and 2 was then studied in mice harboring a chronic S. mansoni infection. A single dose of 1 and 2 (400 mg/kg) resulted in low worm burden reductions of 24% and 29% (p > 0.05). PMID- 24219618 TI - Effect of high-dose paracetamol on needle procedures in children with cancer--an RCT. AB - AIM: The aim was to investigate whether children experience less pain, fear and/or distress when they receive high-dose paracetamol compared with placebo, using a needle insertion in a subcutaneously implanted intravenous port as a model. METHODS: Fifty-one children ranging from 1 to 18 years of age being treated in a paediatric oncology setting were included consecutively when undergoing routine needle insertion into a subcutaneously implanted intravenous port. All children were subjected to one needle insertion following topical anaesthetic (EMLA) application in this double-blind, placebo-controlled RCT, comparing orally administered paracetamol (n = 24) 40 mg/kg body weight (max 2000 mg) with placebo (n = 27). The patients' pain, fear and distress were reported by parents, nurses and children (>=7 years of age) using 0- to 100-mm visual analogue scales (VAS). In addition, pain observation, procedure time and cortisol reduction were assessed. RESULTS: No differences between the paracetamol and the placebo group were found with respect to demographic characteristics. According to VAS reports, paracetamol did not reduce pain, fear and distress compared with placebo. Pain observation, cortisol reduction and procedure time did not differ between the study groups. CONCLUSION: Paracetamol provides no additive effect in reducing pain, fear and distress when combined with topical anaesthesia in children undergoing port needle insertion. PMID- 24219619 TI - They aren't all first cousins: Bedouin marriage and health policies in Lebanon. AB - OBJECTIVE: Fertility and consanguineous marriages among the Bedouin tribes of the Middle East have long generated interest particularly around health outcomes and social relations. In particular, Bedouin in Lebanon have increasingly embraced the Lebanese national bio-medical health system in the past two decades, while Lebanese policy-makers' responses continue to be minimal and ill-informed. This paper investigates the mismatch between policy-makers' formulations of Bedouin consanguineous marriages and the Bedouins's actual reproductive practices and discusses the implications of these formulations on the Bedouins's access to health services. DESIGN: The findings are drawn from the data collected as part of the Bedouin Health Project, an EU-funded five-year study (2005-2010), aiming at assessing access to reproductive and child health care among the Bedouin in Lebanon. The data was collected from 6 clusters representing the main Bedouin informal and unrecognized settlements in the Bekaa Valley of Lebanon. The data consists of 111 socioeconomic questionnaires with Bedouin women users of local public, private, and nongovernmental reproductive and child health-focused clinics, in addition to 40 in-depth interviews with Bedouin women across the clusters and 17 semi-structured interviews with policy-makers. RESULTS: The findings suggest a gap between the perceptions of policy-makers and the incidence of consanguineous marriages and reproductive practices among the Bedouin. While there was no national data available for the Bedouin populations, policy-makers relied on a constructed 'Bedouin reproductive profile' that portrayed them as 'a problematic health group'. The national policy formulation of the Bedouin reproductive profile has an exclusionary impact on the Bedouin population as they are ignored from any targeted health policies or provided with politically motivated palliative care provision. CONCLUSION: These findings highlight the importance of addressing stereotyping and discrimination among health practitioners and policy-makers, as a crucial part of improving the overall marriage and reproductive health practices of the Bedouin. PMID- 24219620 TI - A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study. AB - BACKGROUND: Recent studies suggest that lactation has long-term effects on risk for cardiovascular disease in women, but the effects on cardiovascular mortality are less well known. METHOD: In a Norwegian population-based prospective cohort study, we studied the association of lifetime duration of lactation with cardiovascular mortality in 21,889 women aged 30 to 85 years who attended the second Nord-Trondelag Health Survey (HUNT2) in 1995-1997. The cohort was followed for mortality through 2010 by a linkage with the Cause of Death Registry. Adjusted hazard ratios (HR) for death from all causes and cardiovascular disease were calculated using Cox regression. RESULTS: During follow-up, 1,246 women died from cardiovascular disease. Parous women younger than 65 years who had never lactated had a higher cardiovascular mortality than the reference group of women who had lactated 24 months or more (HR 2.77, 95% confidence interval [CI]: 1.28, 5.99). There was some evidence of a U-shaped association, where women who reported lactating 7-12 months had a HR of 0.55 (95% CI: 0.27, 1.09). No clear associations were observed among women 65 years or older. CONCLUSIONS: Excess cardiovascular mortality rates were observed among parous women younger than 65 years who had never lactated. These findings support the hypothesis that lactation may have long-term influences on maternal cardiovascular health. PMID- 24219622 TI - Design of biomimetic and bioactive cold plasma-modified nanostructured scaffolds for enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells. AB - The objective of this study was to design a biomimetic and bioactive tissue engineered bone construct via a cold atmospheric plasma (CAP) treatment for directed osteogenic differentiation of human bone morrow mesenchymal stem cells (MSCs). Porous nanocrystalline hydroxyapatite/chitosan scaffolds were fabricated via a lyophilization procedure. The nanostructured bone scaffolds were then treated with CAP to create a more favorable surface for cell attachment, proliferation, and differentiation. The CAP-modified scaffolds were characterized via scanning electron microscope, Raman spectrometer, contact angle analyzer, and white light interferometer. In addition, optimal CAP treatment conditions were determined. Our in vitro study shows that MSC adhesion and infiltration were significantly enhanced on CAP modified scaffolds. More importantly, it was demonstrated that CAP-modified nanostructured bone constructs can greatly promote total protein, collagen synthesis, and calcium deposition after 3 weeks of culture, thus making them a promising implantable scaffold for bone regeneration. Moreover, the fibronectin and vitronection adsorption experiments by enzyme linked immunosorbent assay demonstrated that more adhesion-mediated protein adsorption on the CAP-treated scaffolds. Since the initial specific protein absorption on scaffold surfaces can lead to further recruitment as well as activation of favorable cell functions, it is suggested that our enhanced stem cell growth and osteogenic function may be related to more protein adsorption resulting from surface roughness and wettability modification. The CAP modification method used in this study provides a quick one-step process for cell favorable tissue-engineered scaffold architecture remodeling and surface property alteration. PMID- 24219623 TI - Diphenyl diselenide differently modulates cardiovascular redox responses in young adult and middle-aged low-density lipoprotein receptor knockout hypercholesterolemic mice. AB - OBJECTIVES: The present work aimed to investigate the effect of (PhSe)2 on cardiovascular age-related oxidative stress in hypercholesterolemic mice. METHODS: To this end, LDL receptor knockout (LDLr(-/-) ) mice, 3 months (young adult) and 12 months (middle-aged) old, were orally treated with (PhSe)2 . KEY FINDINGS: Hypercholesterolemia, regardless of age, impaired the mitochondrial antioxidant defence in the cardiac tissue, which was characterized by a decline in mitochondrial aortic glutathione (GSH) levels and increased reactive oxygen species production in the heart. (PhSe)2 treatment improved GSH levels, thioredoxin reductase (TRxR) and GSH reductase (GR) activity, and decreased malondialdehyde levels in the heart of young adult LDLr(-/-) mice. Moreover, (PhSe)2 increased GPx activity in both age groups, and GR activity in the aorta of middle-aged LDLr(-/-) mice. CONCLUSIONS: Therefore, (PhSe)2 enhances the antioxidant defences in the cardiovascular system of LDLr(-/-) mice, which could explain its success as an anti-atherogenic compound. PMID- 24219624 TI - Butterfly species richness and diversity in the Trishna Wildlife Sanctuary in South Asia. AB - Several wildlife sanctuaries in the world are home to the surviving populations of many endemic species. Trishna wildlife sanctuary in northeast India is protected by law, and is home to the last surviving populations of Asian bison (Bos gorus Smith), spectacle monkey (Trachypithecus phayrie Blyth), capped langur (Trachypithecus pileatus Blyth), slow loris (Nycticebus coucang Boddaert), wild cat (Felis chaus Schreber), and wild boars (Sus scrofa L.), among many other animals and plants. The sanctuary was explored for species richness and diversity of butterflies. A six-month-long study revealed the occurrence of 59 butterfly species that included 21 unique species and 9 species listed in the threatened category. The mixed moist deciduous mature forest of the sanctuary harbored greater species richness and species diversity (39 species under 31 genera) than other parts of the sanctuary, which is comprised of regenerated secondary mixed deciduous forest (37 species under 32 genera), degraded forests (32 species under 28 genera), and open grassland with patches of plantations and artificial lakes (24 species under 17 genera). The majority of these species showed a distribution range throughout the Indo-Malayan region and Australasia tropics, and eight species were distributed in the eastern parts of South Asia, including one species, Labadea martha (F.), which is distributed in the eastern Himalayas alone. Estimator Chao 2 provided the best-predicted value of species richness. The steep slope of the species accumulation curve suggested the occurrence of a large number of rare species, and a prolonged gentle slope suggested a higher species richness at a higher sample abundance. The species composition of vegetation-rich habitats showed high similarity in comparison to vegetation-poor habitats. PMID- 24219625 TI - Dr M Digby Leigh: his early studies of capnography and their practical application in pediatric cardiac anesthesia. PMID- 24219626 TI - In vitro antidermatophytic activity of Otacanthus azureus (Linden) Ronse essential oil alone and in combination with azoles. AB - AIMS: We determined the chemical composition and investigated the antifungal activity of Otacanthus azureus (Linden) Ronse essential oil (EO) against a range of dermatophytes alone or in combination with azole antifungals. METHODS AND RESULTS: Aerial parts of the plant were steam-distilled and the obtained oil was analysed by gas chromatography/mass spectrometry and (1) H-NMR. It was shown to be largely composed of sesquiterpenes, with the main component being beta-copaen 4-alpha-ol. Using broth microdilution techniques, this oil was found to have remarkable in vitro antifungal activities. Minimum inhibitory concentrations as low as 4 MUg ml(-1) were recorded. The analysis of the combined effect of the O. azureus EO with azoles using chequerboard assays revealed a synergism between the EO and ketoconazole, fluconazole or itraconazole against Trichophyton mentagrophytes. Notably, the O. azureus essential oil showed low cytotoxicity to VERO cells. CONCLUSIONS: The O. azureus essential oil alone or in combination with azoles is a promising antifungal agent in the treatment for human dermatomycoses caused by filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: There is much interest in the study of essential oils for the discovery of new antimicrobial drugs. This study has highlighted the antidermatophytic activity of the O. azureus EO. PMID- 24219627 TI - The oxytocin-bone axis. AB - We recently demonstrated a direct action of oxytocin (OT) on skeletal homeostasis, mainly mediated through stimulation of osteoblasts (OBs) formation and through the reciprocal modulation of osteoclast (OCs) formation and function. Thus, mice lacking the hormone or its receptor develop a low turnover osteoporosis that worsens with age in both sexes. The skeletons of OT (Ot) and OT receptor (Oxtr) null mice display a pronounced decrease in vertebral and femoral trabecular volume. At the cellular level, OBs from Ot KO and Oxtr KO mice exhibit lower mineralization activity and, at the mRNA level, all master genes for osteoblast differentiation are down-regulated. Moreover, OT has dual effects on OCs: it increases osteoclast formation both directly, by activating nuclear factor kB (NFkB) and mitogen-activated protein kinase (MAPK) signalling and, indirectly, through the up-regulation of receptor activator nuclear factor-kappaB ligand synthesis by OBs. On the other hand, it inhibits bone resorption by triggering cytosolic Ca(2+) release and nitric oxide synthesis in mature OCs. OT is locally produced by osteoblasts acting as paracrine-autocrine regulators of bone formation modulated by oestrogens. The oestrogen signal involved in this feedforward circuit is nongenomic because it requires an intact MAPK kinase signal transduction pathway, instead of the classical nuclear translocation of oestrogen receptor. The ability of oestrogen to increase bone mass in vivo is to some extent OXTR-dependent. Thus, Oxtr KO mice injected 17beta-oestradiol did not show any effects on bone formation parameters, whereas the same treatment increases trabecular and cortical bone in wild-type mice. An intact OT autocrine paracrine circuit appears to be essential for optimal skeletal remodelling. PMID- 24219628 TI - Differential satellite cell density of type I and II fibres with lifelong endurance running in old men. AB - AIM: To investigate the influence of lifelong endurance running on the satellite cell pool of type I and type II fibres in healthy human skeletal muscle. METHODS: Muscle biopsies were collected from 15 healthy old trained men (O-Tr) who had been running 43 +/- 16 (mean +/- SD) kilometres a week for 28 +/- 9 years. Twelve age-matched untrained men (O-Un) and a group of young trained and young untrained men were recruited for comparison. Frozen sections were immunohistochemically stained for Pax7, type I myosin and laminin, from which fibre area, the number of satellite cells, and the relationship between these variables were determined. RESULTS: In O-Un and O-Tr, type II fibres were smaller and contained fewer satellite cells than type I fibres. However, when expressed relative to fibre area, the difference in satellite cell content between fibre types was eliminated in O-Tr, but not O-Un. A strong positive relationship between fibre size and satellite cell content was detected in trained individuals. In line with a history of myofibre repair, a greater number of fibres with centrally located myonuclei were detected in O-Tr. CONCLUSION: Lifelong endurance training (i) does not deplete the satellite cell pool and (ii) is associated with a similar density of satellite cells in type I and II fibres despite a failure to preserve the equal fibre type distribution of satellite cells observed in young individuals. Taken together, these data reveal a differential regulation of satellite cell content between fibre types, in young and old healthy men with dramatically different training histories. PMID- 24219630 TI - Three-dimensional graphene foam supported Fe3O4 lithium battery anodes with long cycle life and high rate capability. AB - Fe3O4 has long been regarded as a promising anode material for lithium ion battery due to its high theoretical capacity, earth abundance, low cost, and nontoxic properties. However, up to now no effective and scalable method has been realized to overcome the bottleneck of poor cyclability and low rate capability. In this article, we report a bottom-up strategy assisted by atomic layer deposition to graft bicontinuous mesoporous nanostructure Fe3O4 onto three dimensional graphene foams and directly use the composite as the lithium ion battery anode. This electrode exhibits high reversible capacity and fast charging and discharging capability. A high capacity of 785 mAh/g is achieved at 1C rate and is maintained without decay up to 500 cycles. Moreover, the rate of up to 60C is also demonstrated, rendering a fast discharge potential. To our knowledge, this is the best reported rate performance for Fe3O4 in lithium ion battery to date. PMID- 24219629 TI - CRISPR-MVLST subtyping of Salmonella enterica subsp. enterica serovars Typhimurium and Heidelberg and application in identifying outbreak isolates. AB - BACKGROUND: Salmonella enterica subsp. enterica serovars Typhimurium (S. Typhimurium) and Heidelberg (S. Heidelberg) are major causes of foodborne salmonellosis, accounting for a fifth of all annual salmonellosis cases in the United States. Rapid, efficient and accurate methods for identification are required for routine surveillance and to track specific strains during outbreaks. We used Pulsed-field Gel Electrophoresis (PFGE) and a recently developed molecular subtyping approach termed CRISPR-MVLST that exploits the hypervariable nature of virulence genes and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) to subtype clinical S. Typhimurium and S. Heidelberg isolates. RESULTS: We analyzed a broad set of 175 S. Heidelberg and S. Typhimurium isolates collected over a five-year period. We identified 21 Heidelberg Sequence Types (HSTs) and 37 Typhimurium STs (TSTs) that were represented by 27 and 45 PFGE pulsotypes, respectively, and determined the discriminatory power of each method. CONCLUSIONS: For S. Heidelberg, our data shows that combined typing by both CRISPR-MVLST and PFGE provided a discriminatory power of 0.9213. Importantly, CRISPR-MVLST was able to separate common PFGE patterns such as JF6X01.0022 into distinct STs, thus providing significantly greater discriminatory power. Conversely, we show that subtyping by either CRISPR-MVLST or PFGE independently provides a sufficient discriminatory power (0.9345 and 0.9456, respectively) for S. Typhimurium. Additionally, using isolates from two S. Typhimurium outbreaks, we demonstrate that CRISPR-MVLST provides excellent epidemiologic concordance. PMID- 24219632 TI - Metal contacts on physical vapor deposited monolayer MoS2. AB - The understanding of the metal and transition metal dichalcogenide (TMD) interface is critical for future electronic device technologies based on this new class of two-dimensional semiconductors. Here, we investigate the initial growth of nanometer-thick Pd, Au, and Ag films on monolayer MoS2. Distinct growth morphologies are identified by atomic force microscopy: Pd forms a uniform contact, Au clusters into nanostructures, and Ag forms randomly distributed islands on MoS2. The formation of these different interfaces is elucidated by large-scale spin-polarized density functional theory calculations. Using Raman spectroscopy, we find that the interface homogeneity shows characteristic Raman shifts in E2g(1) and A1g modes. Interestingly, we show that insertion of graphene between metal and MoS2 can effectively decouple MoS2 from the perturbations imparted by metal contacts (e.g., strain), while maintaining an effective electronic coupling between metal contact and MoS2, suggesting that graphene can act as a conductive buffer layer in TMD electronics. PMID- 24219633 TI - Does baseline radiography of the kidneys, ureters, and bladder help facilitate stone management in patients presenting to the emergency department with renal colic? AB - BACKGROUND AND PURPOSE: A baseline kidneys, ureters, and bladder (KUB) radiograph, at the time of computed tomography (CT) for ureteral stones, might aid interpretation of future KUBs. The CT scout radiograph might render the baseline KUB redundant, however. We sought to assess the diagnostic utility of baseline KUB for patients with ureteral stones. PATIENTS AND METHODS: Patients with ureteral stones were retrospectively identified. All had a baseline KUB in addition to CT and were reassessed after 4 to 60 days with KUB. Each patient's imaging was randomized 1:1 into either "KUB&CT" or "CT" groups. Three urologists independently assessed the imaging: CT (with scout film) and baseline KUB in the KUB&CT group, but only the CT (not KUB) in the CT group. Definitive stone assessment on follow-up KUB was defined as all three reviewers answering either Yes or No (not Indeterminate) to the question of stone passage or migration. RESULTS: Of 154 stones, the mean diameter was 4.8 +/- 2.1 mm, density was 914 +/- 300 Hounsfield units (HU), with 54.4% in the distal ureter. Stone visibility was 60.4% on KUB vs 43.5% on scout film (P<0.001). Scout film visibility favored the CT group (52.7 vs 35.0%, P = 0.027). After adjusting for body mass index, skin-to stone distance, size, density, and location, definitive assessment rates were higher in the KUB&CT group (P = 0.047). When reviewers reassessed the CT group using the baseline KUB, they were able to do so definitively in an additional 16 (21.6%, P<0.001). Definitive assessments were associated with higher rates of stone visibility on scout film (86.1 vs 21.1%, P<0.001), KUB (86.1 vs 50.0%, P<0.001), and larger (6.0 vs 3.7 mm, P<0.001), denser stones (1046 vs 802 HU, P<0.001). CONCLUSIONS: The addition of a baseline KUB to the CT scout film improves the ability of urologists to determine stone outcome when following patients with KUB imaging and might reduce the subsequent need for additional imaging. PMID- 24219634 TI - Dietary hydroxyproline induced calcium oxalate lithiasis and associated renal injury in the porcine model. AB - BACKGROUND AND PURPOSE: We previously reported hyperoxaluria and calcium oxalate calculi in adult pigs (sows) fed hydroxyproline (HP). The purpose of this study was to grossly and histopathologically characterize intrarenal effects in this model. METHODS: In the swine facility at our campus, we maintained 21 gestating sows, of which 15 received daily treatment (5% HP mixed with dry feed) and 6 received no treatment (controls). Nine were sacrificed at 21 d (three control, six HP). All kidneys were extracted and examined grossly and for radiographic evidence of stones (GE CT scanner, 80kV, 400MA, 1 sec rotation, 0.625 mm slices). Papillary and cortical samples were processed for histologic analysis. RESULTS: Kidneys from treated sows showed significant calculi distributed within the renal papilla on CT, appeared mottled in the renal cortex and papillary areas, and had less distinct corticomedullary borders. Tiny crystals and mucinous debris lined the papillary tips, calices, and pelvis in kidneys from four of six treated sows, and multiple stones were noted at the papillary tips. Hematoxylin and eosin stain revealed crystals in collecting tubules and papillary tips in treated kidneys and none in controls. Yasue staining confirmed crystals in proximal periglomerular tubules of treated but not control animals. Tubular dilation and inflammatory/fibrotic changes were identified in kidneys from treated animals; none of these changes were evident in control kidneys. CONCLUSIONS: We report renal damage as a result of dietary-induced hyperoxaluria in adult sows. Specifically, we found crystalluria in proximal periglomerular tubules and collecting ducts, with tubular damage at all segments. PMID- 24219635 TI - Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance. AB - Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions. We find that network interactions result in different patterns of mutational (co)variance at the phenotypic level (the M-matrix), not only across network motifs but also across phenotypic space within single motifs. This effect is due almost entirely to mutational input of additive genetic (co)variance. Variation in M has the effect of stretching and bending phenotypic space with respect to evolvability, analogous to the curvature of space-time under general relativity, and similar mathematical tools may apply in each case. We explored the consequences of curvature in mutational variation by simulating adaptation under divergent selection with gene flow. Both standing genetic variation (the G-matrix) and rate of adaptation are constrained by M, so that G and adaptive trajectories are curved across phenotypic space. Under weak selection the phenotypic mean at migration-selection balance also depends on M. PMID- 24219636 TI - Risk factors for musculoskeletal symptoms among Korean radiation workers. AB - The first aim of this study was to determine the prevalence of musculoskeletal symptoms. The second aim was to study the association between musculoskeletal symptoms and factors in radiation workers from the active lists of clinics and hospitals and then to provide basic data for a systematic and effective resource management of radiation workers' musculoskeletal problems in the future. A questionnaire survey was conducted on radiation workers in clinics, general hospitals, and Dong-A university hospitals around the Korean city Buscan from July 10 to 31, 2011. The results showed that the rate of musculoskeletal symptoms was higher in the shoulder, waist, neck, leg/foot, hand/wrist/finger than arm/elbow. The probability of neck pain was 2 times higher in patients with a disease. PMID- 24219637 TI - Obstetric and neonatal outcome in patients with anxiety disorders. AB - OBJECTIVE: To investigate whether a diagnosis of anxiety disorder is a risk factor for adverse obstetric and neonatal outcome. METHODS: A retrospective population-based study was conducted comparing obstetric and neonatal complications in patients with and without a diagnosis of anxiety. Multivariable analysis was performed to control for confounders. RESULTS: During the study period 256,312 singleton deliveries have occurred, out of which 224 (0.09%) were in patients with a diagnosis of an anxiety disorder. Patients with anxiety disorders were older (32.17 +/- 5.1 versus 28.56 +/- 5.9), were more likely to be smokers (7.1% versus 1.1%) and had a higher rate of preterm deliveries (PTD; 15.2% versus 7.9%), as compared with the comparison group. Using a multiple logistic regression model, anxiety disorders were independently associated with advanced maternal age (OR 1.087; 95% CI 1.06-1.11; p = 0.001), smoking (OR 4.51; 95% CI 2.6-7.29; p = 0.001) and preterm labor (OR 1.92; 95% CI 1.32--2.8; p = 0.001). In addition, having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted OR 2.5; 95% CI 1.82-3.46; p < 0.001), using another multivariable model. No association was noted between anxiety disorders and adverse neonatal outcomes including small for gestational age, low Apgar scores and perinatal mortality. CONCLUSION: Anxiety disorders are independent risk factors for spontaneous preterm delivery and cesarean section, but in our population it is not associated with adverse perinatal outcome. PMID- 24219638 TI - Promoting colorectal cancer awareness in undergraduate community health nursing education: a community-academic collaboration. AB - An innovative collaborative partnership between bachelor of science nursing (BSN) students and local public schools was developed in response to a call for increasing awareness of colorectal cancer (CRC) screening in Michigan's underserved populations; through this partnership, community health nursing students provide health education for middle- and high-school aged students who became colon health ambassadors and delivered important messages about the importance of colorectal cancer screenings for their significant others age 50 and older. At the completion, the program reached approximately 1,800 school-age students and their family members. The program provides nursing students with unique service-learning experience while improving their theoretical knowledge and clinical skills in health disparities and community health nursing. The purpose of this article is to describe the development and implementation of this community-academic collaboration and discuss the evaluation of educational outcomes as community health nursing experience. PMID- 24219639 TI - Correlates of lifestyle: physical activity among South Asian Indian immigrants. AB - South Asian immigrants are at increased risk for cardiovascular disease and diabetes, but little is known about their physical activity patterns. In this cross-sectional study, 110 participants were recruited to describe lifestyle physical activity behavior of this at-risk population. Education (p = .042), global health (p = .045), and self-efficacy (p = .000) had significant positive independent effects on leisure-time physical activity. Depression (p = .035) and waist circumference (p = .012) had significant negative independent effects, and frequency of experiencing discrimination a significant positive independent effect (p = .007) on daily step counts. Culture-sensitive physical activity interventions need to target South Asian Indian immigrants who are less educated, in poor health, concerned about racial discrimination, and have low self efficacy. PMID- 24219640 TI - Patient perceptions of empowerment processes, health outcomes and related factors in patients living with diabetes in Taiwan: a cross-sectional survey. AB - BACKGROUND: The aim was to examine the associations among empowerment processes, health outcomes, and related factors in patients living with diabetes. METHODS: This cross-sectional study analyzed a convenience sample of 144 patients with diabetes in Taiwan. Data were collected with questionnaires, HbA1C, blood pressure, and total cholesterol. FINDINGS: Empowerment processes were significantly associated with health outcomes, including self-care behaviors, quality of life, and HbA1C. Diabetes-related complications and treatment variables were associated with empowerment processes and health outcomes. CONCLUSIONS: To optimize the empowerment processes needed to promote the health of patients with diabetes, healthcare professionals should consider patient perceptions of empowerment processes and related factors. PMID- 24219641 TI - Indigenous traditional medicine and intercultural healthcare in Bolivia: a case study from the Potosi region. AB - Indigenous peoples have the worst socio-demographic indicators and the largest inequalities in terms of access to social services and health in the Latin American region, Bolivia included. In the last few years, attempts to implement policies that support indigenous people's health rights led to the development of intercultural health approaches. Yet, acceptance and integration of indigenous medicine into the biomedical health system presents a major challenge to intercultural health in Latin America. The objective of this article is to analyze the case of a health center in Tinguipaya, one of the first and few examples of intercultural health initiatives in Bolivia. This intercultural health project, which represents a pioneer experience with regard to the creation of intercultural health services in Bolivia, aims to create a network between local communities, traditional healers, and biomedical staff and offer a more culturally sensitive and holistic health service for indigenous people living in the area. The aim of this article is to critically assess this initiative and to analyze the main challenges met in the creation of a more effective intercultural health policy. The extent to which this initiative succeeded in promoting the integration between indigenous health practitioners and biomedical staff as well as in improving access to health care for local indigenous patients will also be examined. PMID- 24219642 TI - Current evidence on the attitudes, knowledge and perceptions of nurses regarding evidence-based practice implementation in European community settings: a systematic review. AB - Evidence-based practice (EBP) is an approach that influences healthcare worldwide. Systematic research in the relevant biomedical literature was conducted using the Medline-Pubmed interface until August 2012. Six studies were included in the review. All of these studies had a cross-sectional study design, and 4 of them conducted a postal survey, using different questionnaires for data collection purposes. This review supports previous literature suggesting that community nurses have a positive attitude toward EBP. However, although EBP implementation is considered to be a professional imperative, the integration of recent evidence into clinical practice seems to be a cumbersome process. PMID- 24219644 TI - Use of laser ablation-inductively coupled plasma-time of flight-mass spectrometry to identify the elemental composition of vanilla and determine the geographic origin by discriminant function analysis. AB - A total of 11 elements found in 25 vanilla samples from Uganda, Madagascar, Indonesia, and Papua New Guinea were measured by laser ablation-inductively coupled plasma-time-of-flight-mass spectrometry (LA-ICP-TOF-MS) for the purpose of collecting data that could be used to discriminate among the origins. Pellets were prepared of the samples, and elemental concentrations were obtained on the basis of external calibration curves created using five National Institute of Standards and Technology (NIST) standards and one Chinese standard with (13)C internal standardization. These curves were validated using NIST 1573a (tomato leaves) as a check standard. Discriminant analysis was used to successfully classify the vanilla samples by their origin. Our method illustrates the feasibility of using LA-ICP-TOF-MS with an external calibration curve for high throughput screening of spice screening analysis. PMID- 24219646 TI - Clinical characteristics and prognosis of primary leiomyosarcoma of the pancreas: a systematic review. AB - BACKGROUND: Primary pancreatic leiomyosarcoma (PLMS) is rare. The clinical characteristics and prognosis is still not completely understood. The aim of the present study is to identify the clinical characteristics and long-term outcomes of PLMS from the existing reported cases in different scientific literature. METHODS: PLMS cases reported in Chinese and English journals were collected and reviewed. Clinical features and long-term outcomes of these cases were summarized and analyzed statistically. RESULTS: A total of 69 cases reported from both Chinese and English journals were included in the present study. An equal incidence in gender was observed. The mean age was 53.9 +/- 14.7 years. The most common symptoms were abdominal mass, abdominal pain, and weight loss. The mean size of the tumor was 11.4 +/- 7.1 cm. The incidence of PLMS between the head and body-tail of the pancreas had a similar pattern. Twenty-five percent of patients had distant metastasis and 19% of patients had adjacent organs/vessels invasion at the time of diagnosis. But lymph node metastasis was documented in only one (1.5%) patient. The median survival time was 48 months. The overall 1-, 3-, 5-, and 10-year survival rates were 66.6%, 51.2%, 43.9%, and 29.3%, respectively. Results from the multivariate analysis showed that non-radical resection (P = 0.000; hazard ratio (HR) 5.128; 95% confidence interval (CI) 2.041-12.987) was the independent adverse prognostic factor. Adjacent organs/vessels invasion (yes) may be considered as an another potential independent adverse prognostic factor (P = 0.071; HR 2.708; 95% CI 0.981-7.474). CONCLUSIONS: PLMS is rare without specific clinical features. PLMS is an aggressive tumor and has a poor prognosis. Radical resection can prolong survival time of the patients. PMID- 24219647 TI - Specific IgG4: possible role in the pathogenesis and a new marker in the diagnosis of Anisakis-associated allergic disease. AB - IgG4 and IgE are immunoglobulin isotypes which are mediated by the same Th2 mediated mechanism. The postulated pathogenic and protective function of IgE or IgG4, respectively, in allergic disease is opposite in parasitic infection. The possible role of IgG4 against recombinant major allergens on the appearance of different forms of Anisakis simplex-associated allergic disease was studied. Gastro-allergic anisakiasis (GAA) and Anisakis-sensitization-associated chronic urticaria (CU+) were compared for specific IgE, IgG4 and the respective recognition of Ani s 1 and Ani s 7. Gastro-allergic anisakiasis showed higher IgE and IgG4 levels against crude extract and both recombinant allergens. Whereas IgE recognition of Ani s 7 did not differ and supports both clinical entities to be associated with previous acute parasitism, the IgE recognition rates of Ani s 1 and IgG4 recognition of both Ani s 1 and Ani s 7 were higher in GAA. IgG4 levels were associated with IgE, but also with age, time to last parasitic episode and frequency of fish intake. Logistic regression analysis showed that the presence of specific IgG4 against Ani s 7 was an independent marker associated with GAA. In the diagnosis of Anisakis-associated allergic disease phenotypes (GAA versus CU+), measurement of specific IgG4 against recombinant allergens could be useful. Further, evaluation of specific IgE and IgG4 facilitates more insight into the protective versus pathogenic potential of IgE and IgG4. PMID- 24219648 TI - Clinicopathological significance of the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid in hepatocellular carcinoma. AB - BACKGROUND AND AIM: A faint hypointensity in the noncancerous tissue around hepatocellular carcinoma (HCC) in the hepatobiliary phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) is encountered. The goal is to elucidate the significance of this type of pseudolesion designated as the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd EOB-DTPA) (PDUAE). METHODS: This study group consisted of 61 patients with 61 surgically resected HCCs who underwent preoperative Gd-EOB-DTPA-enhanced MRI. The presence of a faint and hypointense area around the tumor in the hepatobiliary phase was defined as PDUAE. The frequency with which PDUAE was seen was compared between pairs of groups determined by clinical and pathological parameters using a Fisher's exact probability test. The parameters showing significant differences in this test were further tested by multiple logistic regression analysis. RESULTS: PDUAE was observed in 25 cases. In univariate analysis, the values of alpha-fetoprotein and protein-induced by vitamin K absence or antagonist-II, maximal diameter, the presence of a capsule, and vascular invasion were significantly correlated with the frequency with which PDUAE was seen. In multivariate analysis, only maximal diameter and vascular invasion were significantly correlated. When the presence of PDUAE was used as an indicator of vascular invasion, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 72%, 80.6%, 77%, 72%, and 80.6%, respectively. CONCLUSIONS: By using this indicator, "microscopic" vascular invasion of HCC can be easily predicted with Gd-EOB-DTPA-enhanced MRI. PMID- 24219649 TI - Gallic acid improves glucose tolerance and triglyceride concentration in diet induced obesity mice. AB - Gallic acid, a phenolic phytochemical, has been shown to exert a variety of effects, including anti-oxidative, anti- carcinogenic, anti-allergic, and anti inflammatory effects. In this study, we attempted to determine whether gallic acid affects metabolic syndrome such as obesity and diabetes. Diet-induced obesity mice were treated intraperitoneally once per day with gallic acid (10 mg/kg/day). After 2 weeks of treatment, the mice were sacrificed to collect the blood for metabolic parameter assessments, and the adipose tissues and liver to weigh and analyze. The triglyceride concentrations were significantly improved in the gallic acid group relative to those measured in the control group. And most importantly, the blood glucose concentrations in the gallic acid group were significantly improved. In the epididymal white adipose tissue of the gallic acid group, adipocyte size was reduced, PPARgamma expression was induced, and the Akt signaling pathway was activated. Our results demonstrate that gallic acid improves glucose tolerance and lipid metabolism in the obesity mice, thereby showing evidence of anti-hyperglycemic activity. The findings of an upregulation of PPARgamma expression and Akt activation also contribute to our current understanding of the mechanisms underlying the effects of gallic acid on glucose metabolism. PMID- 24219650 TI - Long-term effects of whole body cryostimulation on uric acid concentration in plasma of secondary progressive multiple sclerosis patients. AB - BACKGROUND: Uric acid (UA) has been suggested to be a marker of multiple sclerosis (MS) activity. Whole body cryostimulation (WBCT) is a new form of additional treatment and becoming popular in medicine. OBJECTIVES: The aims of this study were to determine the long-term effects of WBCT on the level of plasma UA in selected group of MS patients only with secondary progressive (SPMS) clinical form and verify results with functional state of patients assessed by expanded disability status scale (EDSS). MATERIALS AND METHODS: SPMS patients (n = 22) and healthy controls (n = 22) participated in 10 3-min-long exposures of WBCT (one exposure per day). Results were collected before the WBCT treatment and after completion the WBCT series as well as one and three months later. RESULTS: WBCT increased UA concentration in plasma of SPMS patients not only directly after 10 exposures (p < 0.0001) but also one (p < 0.0001) and three (p < 0.005) months later. Furthermore, WBCT causes positive changes in EDSS scale both directly after WBCT (7% lower) and maintain this level 1 month later as well as 3 month later (5% lower). CONCLUSIONS: WBCT may be used as adjuvant therapy via increase UA blood level; it improves functional status of SPMS patients. PMID- 24219652 TI - Improvement in smile esthetics following orthodontic treatment: a retrospective study utilizing standardized smile analysis. AB - OBJECTIVE: To quantify smile esthetics following orthodontic treatment and determine whether these changes are correlated to the severity of the initial malocclusion. MATERIALS AND METHODS: A standardized smile mesh analysis that evaluated nine lip-tooth characteristics was applied to two groups of successfully treated patients: group 1 (initial American Board of Orthodontics Discrepancy Index [DI] score<20) and group 2 (initial DI score>20). T-tests were used to detect significant differences between the low-DI and high-DI groups for baseline pretreatment measurements, baseline posttreatment measurements, and changes from pre- to posttreatment. A Spearman correlation test compared the initial DI values with the changes in the nine smile measurements. RESULTS: Five of the smile measurements were improved in both groups following orthodontic treatment. Both groups demonstrated improved incisor exposure, an improved gingival smile line, an increase in smile width, a decreased buccal corridor space, and an improvement in smile consonance. Spearman correlation tests showed that initial DI value was not correlated to changes in any of the individual smile measurements. CONCLUSIONS: Smile esthetics is improved by orthodontic treatment regardless of the initial severity of the malocclusion. In other words, patients with more complex orthodontic issues and their counterparts with minor malocclusions benefitted equally from treatment in terms of their smile esthetics. PMID- 24219654 TI - Controls on methane emissions from Alnus glutinosa saplings. AB - Recent studies have confirmed significant tree-mediated methane emissions in wetlands; however, conditions and processes controlling such emissions are unclear. Here we identify factors that control the emission of methane from Alnus glutinosa. Methane fluxes from the soil surface, tree stem surfaces, leaf surfaces and whole mesocosms, pore water methane concentrations and physiological factors (assimilation rate, stomatal conductance and transpiration) were measured from 4-yr old A. glutinosa trees grown under two artificially controlled water table positions. Up to 64% of methane emitted from the high water-table mesocosms was transported to the atmosphere through A. glutinosa. Stem emissions from 2 to 22 cm above the soil surface accounted for up to 42% of total tree-mediated methane emissions. Methane emissions were not detected from leaves and no relationship existed between leaf surface area and rates of tree-mediated methane emissions. Tree stem methane flux strength was controlled by the amount of methane dissolved in pore water and the density of stem lenticels. Our data show that stem surfaces dominate methane egress from A. glutinosa, suggesting that leaf area index is not a suitable approach for scaling tree-mediated methane emissions from all types of forested wetland. PMID- 24219653 TI - The second study of infectious intestinal disease (IID2): increased rates of recurrent diarrhoea in individuals aged 65 years and above. AB - BACKGROUND: Infectious intestinal disease (IID) is a major health and economic burden in high-income countries. In the UK, there are an estimated 17 million IID cases annually, of which 6 million are caused by the 12 most common pathogens. Host factors that influence risk of IID are not well understood. METHODS: We analyzed data from the IID2 Study, a UK cohort that measured IID incidence, to investigate factors associated with recurrent IID. We calculated rates of IID by age group, sex, previous episodes experienced, and socioecomic indicators. We used Cox models to investigate factors associated with recurrent illness. RESULTS: The rate of IID was five times higher among infants than those aged 65 years and above (hazard ratio, HR = 5.0, 95% CI: 3.1 - 8.0). However, the association between previous IID and a subsequent IID episode was stronger in the elderly. Among those aged 65 years and above, each additional IID episode increased the rate of subsequent IID three-fold (HR = 3.1, 95% CI: 2.5 - 3.7). Among infants, the corresponding increase was 1.7-fold (HR = 1.7, 95% CI: 1.3 - 2.3). CONCLUSIONS: Elderly populations have a high propensity for recurrent IID. More detailed studies are needed to identify vulnerable subgroups and susceptibility factors, and inform adequate control policies among the elderly. PMID- 24219655 TI - Quality of life and well-being of people receiving haemodialysis treatment in Scotland: a cross-sectional survey. AB - End-stage renal disease is a complex, progressive and debilitating illness that affects patients' quality of life, physical and mental health, well-being, social functioning and emotional health. A cross-sectional survey was carried out in renal dialysis centres in Scotland to assess patients' health status and the impact of haemodialysis treatment on quality of life and well-being. Participants scored considerably lower than the UK general population in all domains of health related quality of life, although mental health components were nearer to general population norms than physical health components. However, nearly half of the participants achieved a score on a general well-being questionnaire that was indicative of stress and anxiety. Increasing age was associated with better overall mental health but worse physical functioning. Increasing levels of hope and support were associated with improved general well-being. PMID- 24219656 TI - Interaction of the koinobiont parasitoid Microplitis rufiventris of the cotton leafworm, Spodoptera littoralis, with two entomopathogenic rhabditids, Heterorhabditis bacteriophora and Steinernema carpocapsae. AB - Entomopathogenic nematodes are generally considered beneficial organisms. However, they can affect beneficial insects such as parasitoids. The interaction between the entomopathogenic nematodes Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae) and Steinernema carpocapsae Weiser, and the parasitoid Microplitis rufiventris Kokujev (Hymenoptera: Braconidae) was investigated in the laboratory. In non-parasitized hosts, Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae) larvae exposed to H. bacteriophora showed a higher percent mortality than those exposed to S. carpocapsae. Both nematodes were able to invade and propagate in non-parasitized S. littoralis larvae and those parasitized by M. rufiventris. Both nematode species reproduced in Microplitis-parasitized hosts, but there was a higher number of nematodes in non parasitized larvae. S. carpocapsae yielded higher numbers of infective juveniles than H. bacteriophora. Generally, the number of nematodes harvested increased as their host's size increased. The interaction between the nematodes and parasitoid favored the nematodes when the nematodes were inoculated during the parasitoid egg stage or the young parasitoid larvae, thus giving the nematodes a better chance to grow and reproduce, resulting in the death of the parasitoid larvae. Conversely, when the nematodes were inoculated during the late larval instar of the parasitoid, the competition partially favored the wasp, thus giving approximately 50% of the wasps a better chance to develop, emerge, and reproduce, providing evidence that both nematodes and wasps could reproduce in the same host. Egg maturation of female wasps derived from nematode-infected hosts was not significantly different than those from control hosts. The combined application of nematodes and parasitoids may be beneficial if the detrimental effects of the nematodes on the parasitoid could be avoided by precisely timing the application strategies. It is clear that Microplitis larvae and the nematodes share the host larva and engage in a trophic interaction with each other. Intraguild predation is briefly discussed. PMID- 24219657 TI - Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder. AB - OBJECTIVES: Although several studies have reported on predictors of employment in individuals with bipolar disorder (BD), the magnitude of the impact of these variables is unclear as no previous studies have estimated the collective effect sizes (ESs). The present meta-analysis estimated ESs and explored which of these variables are associated with positive employment outcomes. METHODS: We searched for articles published between 2000 and 2011 that reported associations between sociodemographic, clinical, psychosocial, and/or cognitive variables with employment outcomes in BD. Of the 781 articles identified, 22 met the inclusion criteria and were included in the final analysis (n = 6,301). Weighted correlation coefficients (r-index) were computed as ESs for each of the predictor variables, which were grouped into six categories: cognitive performance, symptomatology, sociodemographic factors, course of illness, clinical variables, and other personal factors. The overall ES (Rw) was estimated by assuming random effect models. Sensitivity analyses were also performed to determine the robustness of the findings. RESULTS: Significant predictors of favorable employment outcomes included: cognitive performance (e.g., verbal memory, Rw = 0.33; executive function, Rw = 0.26), sociodemographic factors (e.g., years of education, Rw = 0.23), course of illness (e.g., number of lifetime psychiatric hospitalizations, Rw = -0.35), symptomatology (e.g., depression, Rw = -0.25), and other personal factors (e.g., personality disorder, Rw = -0.49). CONCLUSIONS: Overall, the cognitive performance and course of illness had larger average ESs than symptomatology or sociodemographic factors on favorable employment outcomes. These findings may help to guide the design of more effective work interventions for people with BD. PMID- 24219658 TI - What became of New Zealand's golden opportunity for liquor law reform? PMID- 24219659 TI - Methamphetamine use in a nationwide online sample of older Australian HIV positive and HIV-negative gay men. AB - INTRODUCTION AND AIMS: Use of methamphetamine appears to be greater among gay men than in the general population, yet little data are available on factors associated with use, especially among older men. This study identifies factors associated with reported methamphetamine use among older Australian gay men. DESIGN AND METHODS: Data were collected from an online survey involving 1135 HIV positive and HIV-negative gay-identified men aged 40 years and older. RESULTS: One in eight men in the sample, or 13%, reported using methamphetamine in the past 12 months. Patterns of reported use were similar across the country, with no significant differences between major states and territories. Reported methamphetamine use was considerably more prevalent among HIV-positive (24%) than HIV-negative men (11%). In a multivariable logistic regression, reported use was significantly greater among men in their 40s compared with those in their 50s and older (P = 0.002), who were single as opposed to being in an ongoing relationship (P = 0.03), who were HIV-positive (P = 0.003), and who reported using other drugs for non-medical purposes in the past 12 months (P < 0.001). Socioeconomic status and psychosocial variables, such as experiences of discrimination and psychological distress, were not significant factors for reported methamphetamine use. DISCUSSION AND CONCLUSIONS: Relatively high rates of reported use of methamphetamine were found across the country in this online sample of older Australian gay men. National approaches to health education strategies may be needed, with a focus on high prevalence populations, such as those infected with HIV. PMID- 24219660 TI - Probing the structural, bonding, and magnetic properties of cobalt coordination complexes: co-benzene, co-pyridine, and co-pyrimidine. AB - Neutral and anionic Co1,2(benzene)1,2, Co1,2(pyridine)1,2, and Co1,2(pyrimidine)1,2 complexes have been investigated within the framework of an all-electron gradient-corrected density functional theory. The ground-state structures for each size clusters were identified based on the geometry optimization. Meanwhile, their electron affinities and vertical detachment energies were predicted and compared with the experimental values. By analyzing the pattern of highest occupied molecular orbitals (HOMOs), we found that the bond formation of these Co-organic complexes mainly arises from the 3d/4s electrons of the cobalt atoms and the pi-cloud of the organic molecules. More importantly, we presented an approach to map and analyze the Co-organic interactions from another perspective. The scatter plots of the reduced density gradient (RDG) versus rho allow us to identify the different types of interactions, and the maps of the gradient isosurfaces show a rich visualization of chemical bond and steric effects. Their magnetic properties were studied by determining the spin magnetic moments and visualizing the spin density distributions. Finally, the natural population analysis (NPA) charge was calculated to achieve a deep insight into the distribution of electron density and the reliable charge-transfer information. PMID- 24219661 TI - Programming effects of FTO in the development of obesity. AB - It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to 'non- or epi-genetic' causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues. PMID- 24219662 TI - Lipopolysaccharide (LPS)-induced autophagy is involved in the restriction of Escherichia coli in peritoneal mesothelial cells. AB - BACKGROUND: Host cell autophagy is implicated in the control of intracellular pathogen. Escherichia coli (E.coli) is the most common organism caused single germ enterobacterial peritonitis during peritoneal dialysis. In this study, we investigated autophagy of peritoneal mesothelial cells and its role in defense against E.coli. RESULTS: Autophagy in human peritoneal mesothelial cell line (HMrSV5) was induced by lipopolysaccharide (LPS) in a dose-dependent and time dependent way, which was demonstrated by increased expression of Beclin-1 and light chain 3 (LC3)-II, the accumulation of punctate green fluorescent protein LC3, and a higher number of monodansylcadaverine-labeled autophagic vacuoles. After incubation of HMrSV5 cells with E.coli following LPS stimulation, both the intracellular bactericidal activity and the co-localization of E.coli (K12 strain) with autophagosomes were enhanced. Conversely, blockade of autophagy with 3-methyladenine, wortmannin or Beclin-1 small-interfering RNA (siRNA) led to a significant reduction in autophagy-associated protein expression, attenuation of intracellular bactericidal activity, and reduced co-localization of E.coli with monodansylcadaverine-labeled autophagosomes. In addition, treatment of HMrSV5 cells with LPS caused a dose-dependent and time-dependent increase in Toll-like receptor 4 (TLR4) expression. Both knockdown of TLR4 with siRNA and pharmacological inhibition of TLR4 with Polymyxin B significantly decreased LPS induced autophagy. Furthermore, TLR4 siRNA attenuated remarkably LPS-induced intracellular bactericidal activity. CONCLUSIONS: Our findings demonstrated for the first time that LPS-induced autophagy in peritoneal mesothelial cells could enhance the intracellular bactericidal activity and the co-localization of E.coli with autophagosomes. The activation of TLR4 signaling was involved in this process. These results indicate that LPS-induced autophagy may be a cell autonomous defense mechanism triggered in peritoneal mesothelial cells in response to E.coli infection. PMID- 24219665 TI - Rights and responsibilities. PMID- 24219673 TI - Emergency consultants claim workload is unsustainable. PMID- 24219674 TI - Community nurses can reduce strain on urgent care staff. PMID- 24219664 TI - Epidermal growth factor receptor targeted nuclear delivery and high-resolution whole cell X-ray imaging of Fe3O4@TiO2 nanoparticles in cancer cells. AB - Sequestration within the cytoplasm often limits the efficacy of therapeutic nanoparticles that have specific subcellular targets. To allow for both cellular and subcellular nanoparticle delivery, we have created epidermal growth factor receptor (EGFR)-targeted Fe3O4@TiO2 nanoparticles that use the native intracellular trafficking of EGFR to improve internalization and nuclear translocation in EGFR-expressing HeLa cells. While bound to EGFR, these nanoparticles do not interfere with the interaction between EGFR and karyopherin beta, a protein that is critical for the translocation of ligand-bound EGFR to the nucleus. Thus, a portion of the EGFR-targeted nanoparticles taken up by the cells also reaches cell nuclei. We were able to track nanoparticle accumulation in cells by flow cytometry and nanoparticle subcellular distribution by confocal fluorescent microscopy indirectly, using fluorescently labeled nanoparticles. More importantly, we imaged and quantified intracellular nanoparticles directly, by their elemental signatures, using X-ray fluorescence microscopy at the Bionanoprobe, the first instrument of its kind in the world. The Bionanoprobe can focus hard X-rays down to a 30 nm spot size to map the positions of chemical elements tomographically within whole frozen-hydrated cells. Finally, we show that photoactivation of targeted nanoparticles in cell nuclei, dependent on successful EGFR nuclear accumulation, induces significantly more double-stranded DNA breaks than photoactivation of nanoparticles that remain exclusively in the cytoplasm. PMID- 24219675 TI - Departments need right skill mix to cope with demand during winter. PMID- 24219680 TI - In pursuit of excellence. PMID- 24219684 TI - Caring for patients at high speed. AB - AIM: The aim of this article is to explore whether ambulance clinicians in Sweden perceive their working environment to be safe. METHOD: Twenty four ambulance nurses and nine paramedics at five ambulance stations in urban and rural areas of Sweden were interviewed. FINDINGS: After transcripts of the interviews had been analysed, nine issues that affect how participants perceive the safety of patient care in ambulances emerged: planning before departure; use of safety belts; driving at high speeds; patient first, safety second; equipment design and placement; noise; driving styles; presence of relatives; documentation. CONCLUSION: Ambulance personnel should have greater involvement in the design of ambulance care spaces and drivers should be given more regular training. PMID- 24219685 TI - Haemorrhage control: lessons from the military. AB - Traumatic injuries with haemorrhage are among the leading causes of death in military and civilian settings. Following recent combat in Afghanistan and Iraq, the UK military has made advances in, for example, first-responder haemorrhage control, massive transfusion protocols and equipment, and it is important that staff in ED settings study the results. With reference to a case study concerning a patient who received a fatal stab wound to his femoral artery, this article examines the haemorrhage-control methods adopted by military and civilian emergency medical services to determine if any lessons can be learned and applied to similar cases. PMID- 24219686 TI - Recognising and managing decompression illness. AB - Seen primarily in scuba divers who have breathed compressed air, decompression illness is a rare but potentially fatal condition. Prompt recognition and treatment of the illness, and urgent referral of patients to hyperbaric chambers, can mean the difference between full recovery and paralysis or death. This article describes decompression illness and how to recognise it, and discusses the treatment that patients require for the best chance of recovery with no adverse effects. It also includes a case study of a patient who developed this condition after a dive. PMID- 24219687 TI - Ingestion or aspiration of foreign bodies by children. AB - Ingestion and aspiration of foreign bodies are common reasons for children presenting to emergency departments. A significant proportion of such events are often unnoticed by the children's parents or carers. Emergency nurses should become suspicious of foreign body ingestion or aspiration if they see symptoms such as stridor, gagging, wheeze and difference in air entry on auscultation ( Hilliard et al 2003 , Paul et al 2010 ). If they suspect airway compromise, or bowel problems such as perforation or obstruction, the children concerned should be dealt with immediately. Definitive management for foreign body removal is generally available at tertiary centres and children should be transferred to specialist services as soon as possible after stabilisation ( McConnell 2013 ). Before discharge, their parents should be educated about possible signs of deterioration and advised about home-safety measures ( Paul and Wilkinson 2012 ). PMID- 24219688 TI - Raising standards. PMID- 24219689 TI - Low- and high-grade bladder cancer determination via human serum-based metabolomics approach. AB - To address the shortcomings of urine cytology and cystoscopy for probing and grading urinary bladder cancer (BC), we applied (1)H nuclear magnetic resonance (NMR) spectroscopy as a surrogate method for the identification of BC. This study includes 99 serum samples comprising low-grade (LG; n = 36) and high-grade (HG; n = 31) BC as well as healthy controls (HC; n = 32). (1)H NMR-derived serum data were analyzed using orthogonal partial least-squares discriminant analysis (OPLS DA). OPLS-DA-derived model validity was confirmed using an internal and external cross-validation. Internal validation was performed using the initial samples (n = 99) data set. External validation was performed on a new batch of suspected BC patients (n = 106) through a double-blind study. Receiver operating characteristic (ROC) curve analysis was also performed. OPLS-DA-derived serum metabolomics (six biomarkers, ROC; 0.99) were able to discriminate 95% of BC cases with 96% sensitivity and 94% specificity when compared to HC. Likewise (three biomarkers, ROC; 0.99), 98% of cases of LG were able to differentiate from HG with 97% sensitivity and 99% specificity. External validation reveals comparable results to the internal validation. (1)H NMR-based serum metabolic screening appears to be a promising and less invasive approach for probing and grading BC in contrast to the highly invasive and painful cystoscopic approach for BC detection. PMID- 24219690 TI - Genetic variants on 17q21 are associated with ankylosing spondylitis susceptibility and severity in a Chinese Han population. AB - OBJECTIVES: The aim of this study was to test whether orosomucoid like 3 (ORMDL3) and 17q21 variants are associated with susceptibility to ankylosing spondylitis (AS) in a Chinese population. METHOD: A total of 753 unrelated AS patients and 1120 ethnically matched healthy controls were recruited. Seven single nucleotide polymorphisms (SNPs: rs7216389, rs12603332, rs12936231, rs9303277, rs11557467, rs1007654, and rs17608925), which were selected from chromosome 17q21 containing the genes ORMDL3, GSDMB, ZPBP2, and IKZF3, were genotyped by the Taqman SNP genotyping assay. RESULTS: Five of the SNPs (rs7216389, rs12603332, rs12936231, rs9303277, and rs11557467) were associated with AS (all p <= 0.01), especially in males (all p < 0.001). Of these, rs7216389, rs12603332, rs12936231, and rs11557467 were strongly associated with severity of the disease based on radiographic findings (p < 0.05). CONCLUSIONS: Our study confirmed that variants in chromosome 17q21 are significantly associated with AS in a Chinese Han population. PMID- 24219691 TI - Prevalence and Risk Factors for Low Back Pain Among Professional Drivers in Kano, Nigeria. AB - This study investigated the prevalence, risk factors, and impact of low back pain (LBP) among professional drivers in Nigeria. Two hundred male drivers aged 19-64 years were recruited in the study. Data regarding prevalence, individual risk factors, and impact of LBP were obtained. The prevalence rate of LBP was 73.5%, and LBP have affected the driving performance of up to 74% drivers. After adjustment for age, LBP prevalence was associated with driving for >15 hours/day (odds ratio [OR]; 95% confidence interval [CI]): (0.04; 0.01, 0.20), driving car (5.52; 1.55, 19.64), and driving bus (10.49; 2.63, 41.82). No association was found between LBP prevalence and years spent driving. The study found that high prevalence of LBP affected the performance of a substantial percentage of the participants. PMID- 24219692 TI - Introduction to the special issue on brain event-related potentials as biomarkers of language and literacy development, feedback, and intervention. PMID- 24219693 TI - Normative topographic ERP analyses of speed of speech processing and grammar before and after grammatical treatment. AB - Typically developing (TD) preschoolers and age-matched preschoolers with specific language impairment (SLI) received event-related potentials (ERPs) to four monosyllabic speech sounds prior to treatment and, in the SLI group, after 6 months of grammatical treatment. Before treatment, the TD group processed speech sounds faster than the SLI group. The SLI group increased the speed of their speech processing after treatment. Posttreatment speed of speech processing predicted later impairment in comprehending phrase elaboration in the SLI group. During the treatment phase, change in speed of speech processing predicted growth rate of grammar in the SLI group. PMID- 24219694 TI - Adequate versus inadequate response to reading intervention: an event-related potentials assessment. AB - Three visual event-related potential components to the second of two sequentially presented words that rhymed or not discriminated children who improved (AR) from those who failed following (IR) reading intervention. Right hemisphere P100 amplitudes discriminated Typically Developing (TD) children from AR children but IR from AR children over left hemisphere sites. N200 amplitudes across hemispheres discriminated TD from IR children and AR from IR children. P300 hemisphere differences differentiated TD from AR and IR children. P300 amplitudes discriminated rhyming from non-rhyming words across children. Results extend prior work asserting that normalization and compensatory mechanisms are active during successful interventions. PMID- 24219695 TI - Auditory event-related potentials measured in kindergarten predict later reading problems at school age. AB - Identifying children at risk for reading problems or dyslexia at kindergarten age could improve support for beginning readers. Brain event-related potentials (ERPs) were measured for temporally complex pseudowords and corresponding non speech stimuli from 6.5-year-old children who participated in behavioral literacy tests again at 9 years in the second grade. Children who had reading problems at school age had larger N250 responses to speech and non-speech stimuli particularly at the left hemisphere. The brain responses also correlated with reading skills. The results suggest that atypical auditory and speech processing are a neural-level risk factor for future reading problems. [Supplementary material is available for this article. Go to the publisher's online edition of Developmental Neuropsychology for the following free supplemental resources: Sound files used in the experiments. Three speech sounds and corresponding non speech sounds with short, intermediate, and long gaps]. PMID- 24219696 TI - An electrophysiological study of print processing in kindergarten: the contribution of the visual n1 as a predictor of reading outcome. AB - Sensitivity to print is characterized by a left occipito-temporal negativity to words in the event-related potential N1. This sensitivity is modulated by reading skills and may thus represent a neural marker of reading competence. Here we studied the development of the N1 in regular and poor readers from preschool age to school age to test whether the amplitude of the N1 predicts children's reading outcomes. Our results suggest a predictive value of the print-sensitive negativity over the right hemisphere. Whether this N1 may serve as a biomarker to improve prognosis in preliterate children should be clarified in future studies. PMID- 24219697 TI - A developmental study of the feedback-related negativity from 10-17 years: age and sex effects for reward versus non-reward. AB - We employed event-related potentials to examine the feedback-related negativity (FRN), during a non-learning reward versus non-reward task. We compared 10-12 year-old, 13-14-year-old, and 15-17-year-old youth (n = 91). Age effects included a larger FRN for younger age groups, regardless of feedback type, and a decrease in peak latency for feedback, across age groups as a linear trend. Males showed larger responses irrespective of feedback type and longer latency for rewarded feedback. Source modeling revealed reward/non-reward differences in the anterior cingulate cortex (ACC) and orbitofrontal cortex, most strongly in the subgenual ACC. Males showed more subgenual ACC activity for feedback overall. PMID- 24219699 TI - Queen signaling in social wasps. AB - Social Hymenoptera are characterized by a reproductive division of labor, whereby queens perform most of the reproduction and workers help to raise her offspring. A long-lasting debate is whether queens maintain this reproductive dominance by manipulating their daughter workers into remaining sterile (queen control), or if instead queens honestly signal their fertility and workers reproduce according to their own evolutionary incentives (queen signaling). Here, we test these competing hypotheses using data from Vespine wasps. We show that in natural colonies of the Saxon wasp, Dolichovespula saxonica, queens emit reliable chemical cues of their true fertility and that these putative queen signals decrease as the colony develops and worker reproduction increases. Moreover, these putative pheromones of D. saxonica show significant conservation with those of Vespula vulgaris and other Vespinae, thereby arguing against fast evolution of signals as a result of a queen-worker arms race ensuing from queen control. Lastly, levels of worker reproduction in these species correspond well with their average colony kin structures, as predicted by the queen signaling hypothesis but not the queen control hypothesis. Altogether, this correlative yet comprehensive analysis provides compelling evidence that honest signaling explains levels of reproductive division of labor in social wasps. PMID- 24219698 TI - Genetic mapping of brain plasticity across development in Williams syndrome: ERP markers of face and language processing. AB - In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, event related potentials (ERPs) from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that, in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing. PMID- 24219700 TI - Development and validation of the eating loss of control scale. AB - Recurrent objective bulimic episodes (OBE) are a defining diagnostic characteristic of binge eating disorder (BED) and bulimia nervosa (BN). OBEs are characterized by experiencing loss of control (LOC) while eating an unusually large quantity of food. Despite nosological importance and complex heterogeneity across patients, measurement of LOC has been assessed dichotomously (present/absent). This study describes the development and initial validation of the Eating Loss of Control Scale (ELOCS), a self-report questionnaire that examines the complexity of the LOC construct. Participants were 168 obese treatment-seeking individuals with BED who completed the Eating Disorder Examination interview and self-report measures. Participants rated their LOC related feelings or behaviors on continuous Likert-type scales and reported the number of LOC episodes in the past 28 days. Principal component analysis identified a single-factor, 18-item scale, which demonstrated good internal reliability (alpha = .90). Frequency of LOC episodes was significantly correlated with frequency of OBEs and subjective bulimic episodes. The ELOCS demonstrated good convergent validity and was significantly correlated with greater eating pathology, greater emotion dysregulation, greater depression, and lower self control but not with body mass index. The findings suggest that the ELOCS is a valid self-report questionnaire that may provide important clinical information regarding experiences of LOC in obese persons with BED. Future research should examine the ELOCS in other eating disorders and nonclinical samples. PMID- 24219702 TI - Invalid survey response patterns among middle school students. AB - Student surveys are widely used to assess student risk behavior, bullying, and school climate in middle schools; however, because such surveys are usually conducted on an anonymous basis, little is known about the validity of student reports using external, independent criteria. This longitudinal study examined the response patterns of 382 middle school students who completed confidential (not anonymous) self-report surveys each fall and spring for 3 years of middle school (Grades 6-8). Approximately 10% of students in each wave indicated on validity screening questions that they were either not telling the truth or not paying attention (termed invalid responders). A repeated measures latent class analysis found that students could be classified into a large group (64%) that was never flagged by the validity questions and a smaller group (36%) that occasionally reported not telling the truth or not paying attention. Hierarchical linear modeling analyses found that invalid responding to validity questions was associated with higher self-reported rates of risk behavior and more negative perceptions of school climate. Based on independent criteria from school records, invalid responding students were more likely to be referred for disciplinary infractions than other students. This study provides new information about student survey validity and appears to be the first to identify characteristics of students who generate invalid response patterns. PMID- 24219701 TI - Measuring parent perceptions of school climate. AB - Parents' attitudes about their children's schools matter. Their views can shape their children's attitudes about school, affect their levels of family-school engagement, and influence their residential and school enrollment decisions. In this article, we describe the development of a survey scale to assess parent perceptions of the climate of their child's school. Our comprehensive scale development process incorporated feedback from academics and potential respondents from the outset of the design process to enhance scale quality. We conducted 3 studies with national samples of parents (n = 385; n = 253; n = 266) to gather evidence of scale score reliability and valid score inferences based on convergent and discriminant validity. Through confirmatory factor analysis, we identified a theoretically grounded factor structure that fit the data well but found no evidence that parental response patterns distinguish between academic and social elements of school climate. Furthermore, we found that parents of younger children, on average, had a more positive perception of the school's climate than did parents of older children. We conclude by discussing how researchers and Pre-K-12 schools and districts can use the scale to aid school improvement efforts. PMID- 24219703 TI - Sadism in sexual offenders: evidence for dimensionality. AB - Recurrent and intense sexual fantasies and urges that circle around the infliction of pain or humiliation on another human being may predispose individuals toward acts of sexual aggression against nonconsenting victims. Consequently, sexual sadism is a paraphilia with particular relevance for forensic psychology and psychiatry. Using behavioral indicators derived from crime scene actions as well as clinical data, we sought in the present study to identify the latent structure of the disorder. We analyzed data from a national sample of male sexual offenders from Austria (N = 1,020). In addition to latent profile analysis, 3 conceptually different taxometric methods were applied. The results of the analyses were more in accordance with a dimensional interpretation than with a categorical distinction. That is, sadistic conduct in sexual offenses is likely an extreme form of coercion, but not a qualitatively different entity. The implications with respect to the current debate on the diagnostic criteria for sadism are discussed. PMID- 24219704 TI - Impact of micromeritic properties of an active pharmaceutical ingredient on its compaction behavior. AB - Physical characteristics of an active pharmaceutical ingredient (API) can have a significant impact on the processability of a high drug loading formulation. This paper provides an example where different micromeritic properties of an API were obtained by crystallization under different conditions, resulting in different tableting behavior. While the API form purity was maintained during the crystallization process change, significant changes were incurred in the surface geometry, porosity and surface area of the API. The batches consisting of particles with greater surface irregularity and porosity gave tablets of higher mechanical strength. PMID- 24219705 TI - VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets. AB - Platelets were activated under the infection with H. pylori in human and mice. We investigated the role of VacA, an exotoxin released by H. pylori in this context. Acid-activated VacA, but not heated VacA, induced platelet CD62P expression. However, VacA reacted with none of the alleged VacA receptors present on platelet membranes. We therefore analyzed VacA associated proteins obtained through VacA affinity chromatography, using MALDI-TOF-MS. Multimerin1 was detected in two consecutive experiments, as the binding protein for VacA. Plasmon resonance confirmed their binding, and dot blot analysis revealed that the peptide sequence AA 321-340 of multimerin 1 is the binding site for VacA. In conclusion, we propose a new interaction between multimerin1 and VacA , which may give another insight into H. pylori-induced platelet activations under H. pylori infection. PMID- 24219706 TI - An extended study of seroprevalence of anti-Anisakis simplex IgE antibodies in Norwegian blood donors. AB - During the last decade, cases of the fish parasite Anisakis simplex infection and allergy in human have increased in countries with high fish consumption. Our aim was to perform an extended seroprevalence study of anti-IgE antibodies against this parasite in Norway, one of the high fish-consuming countries. At the Department of Immunology and Transfusion Medicine and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, two main groups of anonymized serum samples were collected; the first (n = 993) from recently recruited blood donors (designated 'BDO') and the second (n = 414) from patient with total IgE levels >=1000 kU/l (designated 'IGE+'). The sera were analysed by the ImmunoCAP((r)) method for total IgE and IgE antibodies against A. simplex, house dust mite (HDM), shrimp, cod, crab, brine shrimp and shrimp tropomyosin. The A. simplex positive sera were further tested by an enzyme-linked immunosorbent assay (ELISA) method, which uses 2 recombinant (r) major allergens, rAni s 1 and rAni s 7 as target antigens. SDS-PAGE and Western immunoblotting analyses were also performed. Whereas the prevalences by ImmunoCAP((r)) were 0.4% and 16.2% in the BDO and IGE+ groups, respectively, analyses with recombinant allergens showed only 0.0% and 0.2%. Cross-reactivity and immunoblotting analyses suggested that most of the ImmunoCAP((r)) positive sera were probably false positive due to cross-sensitization to shrimp and HDM. However, positivity due to other A. simplex antigens should also be considered. Compared with other high fish-consuming countries, we observed a very low seroprevalence of anti-Anisakis IgE antibodies in a Norwegian population. PMID- 24219708 TI - Our last issue. PMID- 24219709 TI - The definition, aetiology, presentation, diagnosis and management of previous caesarean scar defects. AB - Caesarean sections are the most commonly performed surgical procedures involving the uterus in fertile women. Typically, this surgery involves a transverse incision in the anterior lower uterine segment. The incidence of caesarean sections is on the increase worldwide, and consequently, the complications associated with them are becoming more common. One such complication that is gaining more attention is previous lower uterine segment caesarean scar defect (PCSD). In this review, we sought to explore the definition, aetiology, presentation, diagnosis and management of PCSD. PMID- 24219707 TI - Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies. AB - BACKGROUND AND AIMS: The aim of this study was to examine the distribution of interferon lambda-3 (IFN-lambda3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-lambda3 genotype frequency among the different ethnic populations. METHODS: This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-lambda3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. RESULTS: Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-lambda3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN lambda3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-lambda3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). CONCLUSIONS: The distribution of IFN-lambda3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans. PMID- 24219710 TI - Amnioreduction in a singleton pregnancy: a systematic review. AB - The aim of this study was to investigate the risk of adverse events following amnioreduction in a singleton pregnancy. A systematic review was conducted. Literature was identified by searching two bibliographical databases between 1991 and 2011, without language restrictions. The data extracted and overall rates and confidence intervals for each adverse event were calculated. Four studies met the selection criteria for systematic review. The rate of symptom relief in one study was 100%. Because of the small numbers and wide confidence intervals, an exact quantification of risk of adverse events cannot be determined. PMID- 24219711 TI - Infection and antibiotics in the aetiology, prediction and prevention of preterm birth. AB - Spontaneous preterm labour and delivery is a syndrome comprising diverse pathological pathways that result in labour and delivery before term. It is recognised that multiple pathological processes are involved, and infection has been well studied and firmly established as a cause. Although the molecular mechanisms responsible for this process have been identified, there is a lack of consensus about effective antibiotic intervention. Systematic reviews of the few well conducted studies suggest that antibiotics active against bacterial vaginosis or related organisms (clindamycin) given to appropriate women (those with objective evidence of abnormal genital tract flora), and used early in pregnancy (< 22 completed weeks of gestation) before irreversible inflammatory damage occurs, can reduce the rate of preterm birth. There is a need for well constructed trials to understand the vaginal microbiome and how the different types of maternal immune response influences outcome. PMID- 24219712 TI - Myoinositol: a new marker of intrauterine growth restriction? AB - Inositol is a cyclic sugar alcohol which occurs naturally in a variety of stereoisomers, the most common of which is myo-inositol. Inositol phosphoglycan molecules have been isolated from mammalian tissues and are a major component of the intracellular mediators of insulin action. The fetus with intrauterine growth retardation (IUGR) activates a series of adaptive mechanisms to increase the chances for survival, such as a saving of glucose to ensure nutrition of the vital organs, with a consequent reduction in insulin secretion. It can be hypothesized that the reduced production of fetal insulin leads to an excretion of inositol from the intracellular to the extracellular compartment, with a consequent increase of the metabolite in plasma and urine and a decrease inside the cells. Recently, reports suggesting that the increase in extracellular myo inositol may be a valid marker of an altered glucose metabolism during fetal development in IUGR have been published. PMID- 24219713 TI - Instrumental vaginal delivery--back to basics. AB - Assisted vaginal delivery using forceps or a vacuum extractor is an essential part of obstetric practice. Operative vaginal delivery rates in the UK have remained stable between 10% and 15%, yielding safe and satisfactory outcomes for the majority of mothers and their babies. However, there has been an increase in medico-legal cases due to an increasing awareness of the potential morbidity for both the mother and the baby. There are many factors that can play a part in both the maternal and fetal complications resulting from instrumental deliveries. The aim of this educational review is to address these factors and identify measures to reduce them by adherence to the basics and relevant evidence. PMID- 24219714 TI - Fetal airway management on placental support: limitations and ethical considerations in seven cases. AB - The aim of this study was to evaluate the paediatric and maternal outcome after ex utero intrapartum treatment (EXIT). A retrospective review was carried out of the medical charts (gestational age, circumstances of diagnosis, multidisciplinary prenatal decision, date of surgery, paediatric and maternal outcome) of all the fetuses eligible for/delivered via the EXIT procedure in our paediatrics and obstetrics tertiary care and teaching centre, between October 2004 and May 2011. Seven fetuses with cervical teratoma, epignathus tumour or congenital high airway obstruction syndrome (CHAOS) were included in our study. Two pregnancies were terminated and five fetuses were delivered alive. The airway was secured in all five cases (two endotracheal intubations and three tracheostomies). No maternal complications were observed. On average, babies were delivered at 32 gestational weeks, and spent 31 days in the intensive care unit. All but one baby were ventilated for 18 days. Long-term paediatric outcome was favourable. It is concluded that airway management by the EXIT procedure has become an efficient technique. A multidisciplinary prenatal assessment is essential in order to select appropriate cases. PMID- 24219715 TI - Trends in obstetric research. AB - Never before have opportunities for research in reproductive sciences been so great and never before have relative resources been so limited. The challenge is to increase research studies as they form an integral part of good medicine. It has been suggested that the amount of obstetric medical research in the UK is declining, a major cause for concern, given the scale of morbidity caused by obstetrics disorders. The British Maternal and Fetal Medicine Society hold an annual congress with publication of all abstracts in the Journal of Obstetrics and Gynaecology. This study reviewed abstracts from 1997 to 2007 and categorised the research methodology, serving as a reasonable proxy for the volume of clinical investigation in UK obstetrics. Research studies requiring ethical approval dropped from 30% to 15% of the total in a decade. These figures prognosticate the future of research upon which many advances in medical care depend. PMID- 24219716 TI - Targeted obstetric haemorrhage programme improves incoming resident confidence and knowledge. AB - Postpartum haemorrhage is an infrequent but potentially life-threatening obstetrical emergency amenable to simulation. An educational programme consisting of a lecture and high-fidelity simulation exercise was given to incoming obstetrics and gynaecology (OB) and family medicine (FM) residents. Residents reported pre- and post-intervention confidence scores on a 1-5 Likert scale and a subset completed a postpartum haemorrhage knowledge assessment. Residents reported significant improvements in confidence in parameters involved in diagnosis and management of postpartum haemorrhage. The postpartum haemorrhage test mean scores significantly increased (57.4 +/- 9.6% vs 77.1 +/- 7.9%, p < 0.01) and were significantly correlated to confidence scores (Spearman's coefficient of 0.651, p < 0.001). In conclusion, an education programme that incorporates high-fidelity simulation of postpartum haemorrhage improves the confidence and knowledge of incoming residents and appears to be an effective educational approach. PMID- 24219717 TI - Obstetric consultant weekend on-call shift patterns have no effect on the management of spontaneous labour in a large maternity hospital. AB - Recent reports observe poorer healthcare outcomes during the weekend. Many attribute this weekend effect to a reduced consultant presence. This study evaluates differences in labour management on weekends vs weekdays. A total of 20,187 deliveries, all resulting from spontaneous labour, in the same large U.K. maternity hospital were examined. Labour management was analysed both for the department as a whole, and separately for each consultant, for differences in weekend and weekday practice. Results showed no statistically significant results of a difference in any of the measures analysed. On a weekend, deliveries were no more likely to be vaginal, p = 0.485, assisted, p = 0.771 or by caesarean section, p = 0.526. There was also no difference between individual consultants. It was concluded that for spontaneous labour, there is no difference in patient management on weekends vs weekdays, either in the department as a whole, or between individual consultants in our study. PMID- 24219718 TI - Increased incidence of placenta praevia and accreta with previous caesareans--a hypothesis for causation. AB - With the increasing numbers of caesareans, long-term complications, such as anterior placenta praevia-accreta are becoming important. Two case reports are presented here, leading to a hypothesis that the increasing incidence of anterior placenta praevia after prior caesareans may be a result of excessive differential development of the lower uterine segment. This could result from marked stretching of a poorly-healed myometrial area by the developing placenta. This would explain the lower incidence of 'apparent' migration of low placenta, as well as the higher likelihood of morbid adhesion. Although different operative techniques do not have a significant effect on short-term outcomes of caesareans, they are likely to impact the long-term complications. In the absence of long term studies and good quality evidence, theoretical and logical analysis suggests that adherence to good surgical techniques, such as gentle tissue handling, haemostasis, good myometrial approximation without compromising blood supply and restoration of normal anatomy, may reduce long-term complications. PMID- 24219719 TI - Comparison of scar thickness measurements using trans-vaginal sonography and MRI in cases of pregnancy with previous caesarean section. Do they correlate with actual scar thickness? AB - The aim of this study was to evaluate scar thickness in cases of pregnancy with previous caesarean section, by trans-vaginal sonography (TVS) and magnetic resonance imaging (MRI), and to correlate precision of radiologically-measured scar thickness with actual measurement of scar thickness. A total of 35 pregnant patients with previous caesarean section planned for elective caesarean section, were evaluated prospectively. Their scar thickness was measured by TVS and MRI on the day of elective repeat caesarean section. These measurements were correlated with each other and with scar thickness measured during elective repeat caesarean section by using a caliper. The correlation coefficients between scar thickness measured by TVS and MRI with peroperative evaluation with a caliper, were +0.72 and +0.59, respectively. The study concluded that as MRI is a costlier modality and TVS has better correlation coefficient with actual scar thickness, TVS can be considered to be the better modality for antenatal scar thickness measurement. PMID- 24219720 TI - Listeria awareness among recently delivered mothers. AB - The level of knowledge of Listeria among mothers in Ireland is unknown. This prospective questionnaire study aims to evaluate the level of knowledge of recently delivered mothers regarding Listeria infection and its potential prevention. A response rate of 98% was achieved. A total of 271 (43.9%) mothers had heard about Listeria infection but only 187 (30.3%) knew that it was a food borne pathogen. In total, 83 (13.5%) mothers recalled being told about Listeria infection by a midwife or doctor and 33 (5.3%) recalled receiving written information. A total of 224 (36.3%) of mothers were aware of the increased risk of listeriosis during pregnancy, while 250 (40.5%) knew the potential complications to the unborn fetus. A grand total of 505 (81.8%) mothers knew that they should avoid certain high-risk foods during pregnancy but 342 (55.4%) admitted to having consumed high-risk foods during their pregnancy. In conclusion, mothers' knowledge about listeriosis and its prevention was limited. Many mothers ate high-risk food during pregnancy. Antenatal advice regarding Listeria prevention needs to be improved. PMID- 24219721 TI - Hepatic portal vein flow and three dimensional indices of hepatic perfusion in pre-eclampsia compared with normal pregnancy. AB - It has been suggested that the origins of pre-eclampsia arise from the maternal venous system dysfunction. This study aimed to test this hypothesis by assessing hepatic perfusion in pre-eclampsia using three-dimensional (3D) ultrasound. The hepatic portal vein flow in 12 women with normal pregnancy and 11 women with pre eclampsia was measured using standard Doppler ultrasound. The 3D indices of hepatic perfusion: flow index (FI), vascular index (VI) and vascularisation flow index (VFI), which are believed to reflect vascularity and flow intensity were also measured. Because of small numbers, a non-parametric test was used to test differences between groups. Hepatic portal vein flow was no different between women with normal pregnancy compared with women with pre-eclampsia (228.1 (215.5 270.6) vs. 283.0 (145.9-344.6); p = 0.90). The 3D indices of hepatic perfusion were as follows (FI: 36.3(30.7-42.5) vs. 39.7 (27.7-44.2), p = 1.00; VI: 11.7 (3.6-21.2) vs. 3.0 (0.5-7.6), p = 0.04; VFI: 4.7 (1.2-8.3) vs. 1.2 (0.1-3.2), p = 0.06, respectively). This study was not able to support or refute the suggestion that the genesis of pre-eclampsia arises from the maternal venous circulation. There may be biological differences in the 3D indices of hepatic perfusion in women with pre-eclampsia compared with normal pregnant women. PMID- 24219722 TI - Robotic-assisted prophylactic transabdominal cervical cerclage in singleton pregnancies. PMID- 24219723 TI - Twin's sex and risk of pre-term birth. AB - Male sex is a risk factor for pre-term birth (PTB) among singleton pregnancies; however, in twin pregnancies, the effect of sex on PTB is not yet clear. The aim of this study was to evaluate the effect of twin's sex on risk of PTB. During this analytical cross-sectional study, we evaluated the effect of twin's sex, chorionicity and other factors on risk of PTB in 676 pregnant women in a university hospital in Tehran, Iran. Existence of male gender in pregnancy was a risk factor for PTB. Comparing same sex twins together, male-male gender was a risk factor for PTB (OR = 1.67 (1.19-2.34), p = 0.002), early PTB (OR = 1.18 (1.04-1.34), p = 0.01) and very early PTB (OR = 1.06 (1-1.13), p = 0.04). Monoamnion twins were at higher risk for early PTB (OR = 1.44 (1.08-1.92), p = 0.02), and very early PTB (OR = 1.95 (1.1-3.44), p = 0.03) but the risk did not increase in monochorion twins. History of abortion was also shown to be a risk factor (p < 0.05). Maternal age, multiparity, body mass index (BMI) and assisted reproductive techniques (ART) did not reach the significance levels to be considered as risk factors. PMID- 24219724 TI - Prenatal diagnosis of sex chromosome aneuploidies: experience at a mainland Chinese hospital. AB - The aim of this study is to assess the initial indications, frequency and termination rates of pregnancies with sex chromosome aneuploidies (SCAs), at a mainland Chinese hospital. A total of 56 cases (0.9%) with SCAs were identified in 6,515 pregnancies referred for fetal karyotyping. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (48.2%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. The main reasons for fetal karyotyping in other types of SCAs were a positive prenatal screening test and advanced maternal age. A total of 47 (84%) of the pregnancies with SCAs were terminated and nine (16%) continued. This study first reported the rate of SCAs detected at prenatal diagnosis and the outcomes of these pregnancies in mainland China, and showed a very high termination rate for pregnancies with SCAs. PMID- 24219725 TI - The effect of a Foley catheter balloon on cervical ripening. AB - The Foley catheter balloon may affect cervical ripening through changes in biochemical mediators by immunoassay and immunohistochemistry, when it is used for pre-induction cervical ripening. The aim of the study was to evaluate the changes in the biochemical mediators from the extra-amniotic space and immunohistochemistry in ripened cervical tissue after the insertion of a Foley catheter balloon (FCB) for pre-induction cervical ripening. A total of 18 pregnant women with a Bishop's score < 6, who were undergoing labour induction, were evaluated in this prospective study. The FCB was irrigated with 10 ml of phosphate buffered saline and the irrigant was collected 0, 2, 4 and 8 h after placement of the FCB or until spontaneous expulsion of the FCB occurred. Irrigant specimens were also collected from 10 spontaneous labouring (SL) women in the active phase of labour. The levels of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-8 and NO were measured. Cervical specimens were obtained from 12 women, including four undergoing induction; four SL and four non-pregnant (NP) women. Immunohistochemical staining was performed to localise hyaluronic acid synthase (HAS)-1, IL-6, IL-8, MMP-8, endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS). Results showed that the levels of IL-6, IL-8, and MMP-8 significantly increased over time in FCB group (p < 0.01). In the immunohistochemical analysis of cervical tissues, immunoreactivity of HAS-1 in the after FCB group was stronger than any of the other groups. The protein expressions of IL-6, IL-8, MMP-8, eNOS and iNOS were more prominent in the after FCB and SL groups than in the NP and the before FCB groups. iNOS was only observed in the after FCB and SL groups. It was concluded that FCB may affect cervical ripening through changes in biochemical mediators by immunoassay and immunohistochemistry, when it is used for pre-induction cervical ripening. PMID- 24219726 TI - Patient awareness and acceptability of antenatal perineal massage. AB - Antenatal perineal massage is recommended to reduce perineal trauma at the time of delivery. The practice has been shown to be acceptable to pregnant women taking part in research studies. The aim of this study was to establish its acceptability to pregnant women in day-to-day clinical practice, as well as their awareness of its technique. An anonymous self-construct questionnaire was given to mothers after their first delivery. A total of 113 questionnaires were returned over a 4-month period. With regard to acceptability, 61.4% of respondents indicated that the practice was acceptable, only 25.7% felt the practice was embarrassing and 56.7% were happy for their husband/partner to perform it for them. With respect to awareness, 37.2% of the respondents had heard about the practice, 9.7% knew it should be practised from 34 weeks onwards, 11.5% knew it should be maintained for 5-10 min and 30.1% knew it ought to be performed daily. This showed first time mothers' awareness of antenatal perineal massage to be low, despite the idea being acceptable to them, which calls for action to improve awareness and provide more instruction and encouragement to take up the practice. PMID- 24219727 TI - Trends in obstetric anal sphincter injuries over 10 years. AB - Obstetric anal sphincter injuries (OASIS) is a known complication of vaginal delivery and has significant public health issues, as it can cause both short- and long-term morbidity in women. The most commonly reported complications include different grades of faecal/flatus incontinence, pain and sexual dysfunction. In our study, we found a rising trend in OASIS rates in vaginal deliveries, with the rising rate of forceps and the falling rate of SVD, which is at least partly due to increased awareness and training in OASIS. However, there is an actual increase in the number of such tears at vaginal deliveries. Midwifery and obstetric practices have certainly changed over the last decade and we discuss the possible factors, which might be contributing to such a rise. PMID- 24219728 TI - Candida vaginitis during contraceptive use: the influence of methods, antifungal susceptibility and virulence patterns. AB - No consensus exists about whether contraceptives cause an increased risk of vaginitis, including vulvovaginal candidosis (VVC). We investigated 495 women (252 who used contraceptives; 243 who did not) for the presence of VVC. Antifungal susceptibility testing was performed for five antifungal agents and for boric acid, and three virulence factors were also examined. We recovered 129 (26.1%) monofungal populations from vaginal samples of women with acute VVC (AVVC, n = 18), symptomatic recurrent VVC (RVVC, n = 22) and asymptomatic RVVC (n = 28), as well as of other contraceptive users who carried Candida in their vaginas (n = 61). It is important to note that the women who had VVC used the same contraceptive methods (p > 0.05). Candida albicans was the most common species isolated (45%), followed by C. glabrata (40.3%). Most of the vaginal yeast isolates exhibited low minimum inhibitory concentration levels for the five antifungals tested. However, this was not the case for boric acid. In addition, the yeast fungi that was derived from the AVVC and RVVC patients showed higher amounts of haemolytic activity than the yeast fungi found among the controls (p < 0.05). The use of contraception does not predispose women to VVC (p > 0.05). Also, both host- and organism-related factors were required to achieve optimal clinical treatment for VVC. PMID- 24219729 TI - Can anti-Mullerian hormone be predictive of spontaneous onset of pregnancy in women with unexplained infertility? AB - The objective of the study was to assess anti-Mullerian hormone's (AMH) role in predicting spontaneous onset of pregnancy. This observational cohort study included 83 women with unexplained infertility and normal or low ovarian reserve. Serum AMH, FSH, LH, 17beta-oestradiol, inhibin B levels were measured and the number of early antral follicles (2-9 mm) was evaluated on days 2-5 of the cycle. Spearman's correlation was used for comparison of strength of correlation. The diagnostic power of AMH in predicting spontaneous pregnancy was evaluated by receiver operating characteristic (ROC) curves. Markers of ovarian reserve in pregnant women and women without pregnancy were similar. In the entire study population, any markers (AMH, FSH, AFC, age), correlated with each other, but no marker was correlated with pregnancy. The area under the ROC curve for AMH reached a value of 0.385 +/- 0.07 (0.25-0.52, 95% confidence interval, CI); for FSH 0.415 +/- 0.08 (0.25-0.58, 95% CI); for AFC 0.418 +/- 0.08 (0.26-0.57, 95% CI), for age 0.496 +/- 0.08 (0.34-0.65, 95% CI). The study did not find a predictive role for AMH in predicting spontaneous onset of pregnancy. Even when AMH levels are very low, a spontaneous pregnancy may still occur. PMID- 24219730 TI - Relationship of thyroid hormone levels and thyroid autoantibodies with early pregnancy loss and infertility. AB - Prevalence of abnormalities in thyroid hormones and thyroid autoantibodies in patients with a history of early pregnancy loss (EPL) (n = 17) and unexplained infertility (UI) (n = 25), were compared with that of 45 control patients. TSH, antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) antibody levels in UI and EPL groups were similar to that of the control group. TSH was normal in 39, 22 and 13 of control, UI and EPL patients, respectively. Among patients with a normal TSH, fT4 was higher (p < 0.001) and fT3 was lower (p < 0.001) in infertile patients when compared with the control group. Thyroid function tests seem to be associated with infertility but their association with EPL is weaker. Infertility seems to be associated with a high fT4 and low fT3 status. Thyroid autoantibodies do not seem to be associated with either infertility or EPL. PMID- 24219731 TI - Risk factors for rape re-victimisation: a retrospective analysis. AB - Sexual re-victimisation refers to a pattern in which the sexual assault victim has an increased risk of subsequent victimisation relative to an individual who was never victimised. The purpose of our study was to identify risks factors for a second rape, the severest form of sexual re-victimisation. All rape victims treated at the First Regional Israeli Center for Sexual Assault Victims between October 2000 and July 2010 were included in this retrospective analysis. We compared characteristics of 53 rape victims who were victimised twice to those of 1,939 rape victims who were victimised once. We identified several risk factors for a second rape, which can be used in prevention programmes. These are: psychiatric background, history of social services involvement, adulthood, non virginity and minority ethnicity. PMID- 24219732 TI - NT-proBNP levels in premenopausal women with polycystic ovarian syndrome and/or obesity. AB - According to some studies, polycystic ovarian syndrome (PCOS) patients have an increased risk for diabetes mellitus and often show an adverse cardiovascular risk profile. NT-proBNP was shown to have a high predictive value regarding cardiovascular events, especially in those without overt cardiovascular disease. The aim of this study was to investigate the levels of NT-proBNP in 70 women with PCOS and/or obesity in relation to other classical cardiovascular risk factors. There was no statistical difference between NT-proBNP levels between obese, lean PCOS and obese PCOS patients; between patients with or without metabolic syndrome; or between patients with different cardiovascular risk, according to The Androgen Excess and PCOS Society consensus. NT-proBNP does not show significant correlation to age, weight, BMI, WHR, WSR, systolic or diastolic blood pressure and results from oral glucose tolerance test (OGTT), except for immunoreactive insulin (IRI) at 120 min. NT-proBNP correlates weakly with HDL, but not with other indices of lipid metabolism. PMID- 24219733 TI - The effect of age on pressure flow parameters in women with lower urinary tract symptoms. AB - This study aimed to evaluate changes in voiding with age in women with different urodynamic diagnoses. Correlation was used to analyse the association between age and voiding parameters (maximum flow rate, voided volume, flow rate centile and maximum detrusor pressure - PdetMax) in 896 datasets. Multivariate analysis was used to analyse the data further by age group and diagnosis - urodynamic stress incontinence (USI); detrusor overactivity (DO); mixed USI and DO; no urodynamic abnormality. Results showed that diagnosis accounts for a significant amount of variation in all four of the dependent variables Age group shows a significant effect on voiding volume but does not show significant effects on any other variable studied. There is no significant interaction term in any of the analyses, meaning that age and diagnosis do not appear to function together, e.g. age does not relate to flow rate centile, maximum flow rate or PdetQMax. It was concluded that the data suggest that there is no significant change in voiding function related to age. In the elderly, the main alteration in voiding is due to a higher prevalence of DO. PMID- 24219734 TI - Ets-1 regulates its target genes mainly by DNA methylation in human ovarian cancer. AB - Ovarian cancer is the second most common gynaecological cancer worldwide, and its molecular mechanism has not been completely understood. Ets-1 is a member of the Ets transcription family and can play important roles in the regulation of extracellular matrix remodelling, invasion, angiogenesis and drug resistance in several malignancies, including ovarian cancer. In the current study, we downloaded two datasets from Gene Expression Omnibus database and sought to explore the regulation mechanism of Ets-1 in ovarian cancer by computational analysis of gene expression profiles. Microarray analysis identified a total of 548 genes that were regulated by Ets-1 in ovarian cancer. Functional annotation of these genes revealed that Ets-1 may be involved in several biological processes, both physiological and pathological, such as system development, response to stimulus, vascular endothelial growth factor (VEGF) production, morphogenesis, cell proliferation, cell adhesion and signal transduction. Further, DNA methylation analysis of the DEGs found that 26.5% (145) of them were differentially methylated genes in ovarian cancer. Our results provide insight into the mechanism of Ets-1 regulating the transcription of its target genes in the complex and multistep process of ovarian cancer progression. PMID- 24219735 TI - Early-stage cervical carcinoma: the role of multidetector CT in correlation with histopathological findings. AB - The objective of this retrospective study was to assess the diagnostic performance of multidetector CT (MDCT) in staging patients with surgical pathological proven early-stage cervical carcinoma. A total of 22 women were referred for preoperative staging by MDCT, on a 16-row CT scanner. The protocol included scanning of the abdomen during the portal phase using a detector collimation of 16 * 0.75 mm and a pitch of 1.2. The evaluated parameters were: tumour detection, tumour maximal diameter, tumour extension to the uterine body and/or the vagina, parametrial invasion and presence of pelvic lymph node metastases. CT stage was assigned for each cervical carcinoma. The surgical pathological stage was assigned on the basis of the operative findings and the histology report. The overall accuracy of MDCT in detecting and staging primary cervical carcinoma was 86% and 86%, respectively. Our results showed good diagnostic performance of MDCT in the detection and local staging of early-stage cervical carcinoma. PMID- 24219736 TI - Simplified staging laparotomy in FIGO stage 1 epithelial ovarian cancer: follow up and outcomes in south Wales, U.K. AB - We have conducted a retrospective analysis of FIGO stage 1 ovarian cancer patients in south Wales, who underwent a simplified staging laparotomy without routine nodal sampling and peritoneal biopsies. Patient records from January 2004 to December 2010 were analysed. A total of 116 patients were included in the final analysis. Adjuvant chemotherapy was offered to patients with risk factors for relapse (grade > 1, clear cell histology, or stage > Ia); overall, 89 patients (76.7%) received adjuvant single agent carboplatin (n = 54, 46.5%) or combination chemotherapy (n = 35, 30.2%). After a median follow up of 41 months (range 12-95), 18 patients have relapsed (15.5%), of these 17 had risk factors and 16 had received adjuvant chemotherapy. Eighteen patients have died, of whom 6 of non-cancer related causes without prior relapse. 5-year overall and relapse free survival were 80%. In conclusion, in situations where there are limited resources and operating time constraints, our data suggest that a simplified staging laparotomy approach may be a reasonable compromise in apparently early stage ovarian cancer: this may result in a more aggressive use of chemotherapy, but survival outcomes seem comparable to other series. PMID- 24219737 TI - The use of sentinel node sampling in vulval cancer. AB - Between March 2007 and December 2009, 38 patients underwent sentinel lymph node biopsy (SLNB) sampling, along with vulvectomy, in their management of vulval cancer. A review has been conducted to establish the reliability and accuracy of the new procedure compared with the traditional total inguinofemoral lymphadenectomy. We also aimed to establish both the short- and long-term morbidities of both total inguinofemoral lymphadenectomy and SLNB and to assess the duration of hospital stay in both groups. Our data have shown a reduced short and long-term morbidity and reduced length of hospital stay for the SLNB procedure. We conclude that it is a reliable and safe procedure, however it should only be conducted in cancer centres. PMID- 24219738 TI - VIA screening for cervical cancer in developing countries: potential role of the light source. AB - A total of 385 symptomatic patients presenting to the gynaecology and obstetrics outpatient department were screened by two sources of light: the yellow light of the tungsten bulb and the white light of the halogen bulb (100 Watt, 12 Volt), fitted with KODAK 80B filter and diffuser in an instrument called a 'Magnivisualizer' (developed by our Institute). Colposcopic examination was the gold standard for visualisation of the cervix. This study clearly brings out the significance of visual examination of the cervix using white light; as, in addition to having perfect correlation with colposcopy (0.86 for white vs 0.53 for yellow light), white light enables us to select the correct site of biopsy. Most of the rural clinics use torch or ordinary tungsten bulb, thus missing many significant lesions. In the light of our research findings, we strongly recommend the use of white light (complete spectrum of light) for screening purposes. PMID- 24219739 TI - Pseudohypoparathyroidism type 1a in pregnancy. PMID- 24219740 TI - Congenital anomalies presenting in utero as TTTS: a case series report and review of literature. PMID- 24219741 TI - Impaired DNA methylation leading to heterotrisomy. PMID- 24219742 TI - Management of vasa praevia: a potential role for cervical length and quantitative fetal fibronectin measurement. PMID- 24219743 TI - Uterocutaneous fistula following classical caesarean delivery for placenta percreta with intentional retention of the placenta. PMID- 24219744 TI - Vulval haematoma after TVT-obturator insertion requiring arterial embolisation. PMID- 24219745 TI - Laparoscopic oophorectomy: a novel means of treatment for virilisation. PMID- 24219746 TI - Extrapulmonary lymphangioleiomyomatosis complicated by vesicovaginal fistula. PMID- 24219747 TI - Gestational choriocarcinoma in the fallopian tube. PMID- 24219748 TI - Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus. PMID- 24219751 TI - UV-laser-based microscopic dissection of tree rings - a novel sampling tool for delta(13) C and delta(18) O studies. AB - UV-laser-based microscopic systems were utilized to dissect and sample organic tissue for stable isotope measurements from thin wood cross-sections. We tested UV-laser-based microscopic tissue dissection in practice for high-resolution isotopic analyses (delta(13) C/delta(18) O) on thin cross-sections from different tree species. The method allows serial isolation of tissue of any shape and from millimetre down to micrometre scales. On-screen pre-defined areas of interest were automatically dissected and collected for mass spectrometric analysis. Three examples of high-resolution isotopic analyses revealed that: in comparison to delta(13) C of xylem cells, woody ray parenchyma of deciduous trees have the same year-to-year variability, but reveal offsets that are opposite in sign depending on whether wholewood or cellulose is considered; high-resolution tree-ring delta(18) O profiles of Indonesian teak reflect monsoonal rainfall patterns and are sensitive to rainfall extremes caused by ENSO; and seasonal moisture signals in intra-tree-ring delta(18) O of white pine are weighted by nonlinear intra annual growth dynamics. The applications demonstrate that the use of UV-laser based microscopic dissection allows for sampling plant tissue at ultrahigh resolution and unprecedented precision. This new technique facilitates sampling for stable isotope analysis of anatomical plant traits like combined tree eco physiological, wood anatomical and dendroclimatological studies. PMID- 24219750 TI - Characterization of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes. AB - The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline in both Australia and globally. Hence, the cellular and molecular pathways that are associated with UVR-induced photocarcinogenesis need to be urgently elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular, the highly mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which, to some extent, have limited their relevance to the in vivo situation. To address this, we characterized a three-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53, and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration after photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage. PMID- 24219752 TI - Improving the odds of success in drug discovery: choosing the best compounds for in vivo toxicology studies. AB - A set of molecules that advanced into exploratory animal toxicology studies (two species) was examined to determine what properties contributed to success in these safety studies. Compounds were rigorously evaluated across numerous safety end points and classified as "pass" if a suitable in vivo therapeutic index (TI) was achieved for advancement into regulatory toxicology studies. The most predictive end point contributing to compound survival was a predicted human efficacious concentration (Ceff) of <=250 nM (total drug) and <=40 nM (free drug). This trend held across a wide range of CNS modes of action, encompassing targets such as enzymes, G-protein-coupled receptors, ion channels, and transporters. PMID- 24219753 TI - The effects of a catheter clamping protocol on bladder function in neurosurgical patients: a controlled trial. AB - There is scant evidence-based literature on the best strategies for short-term urinary catheter removal. This clinical trial explored the effects of an early urinary catheter clamping protocol on bladder function in neurosurgical patients. Eligible patients were divided into observation and control groups. Those in the observation group had their catheter clamped postoperatively on return to the ward and unclamped at dedicated intervals. The control group received standard care; the catheter was on free drainage during the entire time in situ. The mean catheter indwelling time was 2.6 days. Compared with the control group, the observation group experienced shorter time to first postoperative urination, less residual urine volume and better subjective perception during their first postoperative urination. For patients undergoing neurosurgery and associated short-term indwelling urinary catheterization, an early catheter clamping protocol is effective in facilitating bladder function, reducing the rate of dysuria and making patients feel more comfortable after catheter removal. PMID- 24219754 TI - Dull plots, pale colors early in the morning. AB - Resetting of the circadian clocks involves the heat shock pathway. Cryptochromes as the actual repressors take care of circadian alignment, and in addition they link the circadian clocks to temperature responses, metabolic homeostasis, and sleep homeostasis. In contrast, circadian misalignment redistributes rapid-eye movement sleep and has ramifications for the insulin pathway, inflammation, weight control, and mood. Here, the second half of the night and the actions of cryptochromes are suggested to be a critical period and a key mechanism, respectively. PMID- 24219755 TI - Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. AB - Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory. PMID- 24219756 TI - Early peak height velocity and cardiovascular disease mortality among Icelandic women. AB - INTRODUCTION: Early pubertal onset among girls has been associated with cardiovascular disease (CVD) risk factors. We examined whether timing of peak height velocity (PHV), an early marker of maturity, was associated with CVD mortality. MATERIALS AND METHODS: We analysed 973 Icelandic women, born 1921 1935, with annual childhood growth measures from ages 8-13 years, recruited into the longitudinal Reykjavik study 1968-1991. CVD deaths from recruitment to December 2009 were recorded. RESULTS: Eighty-six women died from CVD, 42 deaths from coronary heart disease (CHD). Compared to girls with PHV after age 12, girls with PHV < 11 years and between 11 and 12 years had greater risk of CVD mortality, hazard ratio 1.87 (95% confidence interval 1.07-3.26, P = 0.028) and 2.56 (1.52-4.31, P < 0.001), respectively. Comparable associations were observed with CHD cases 2.27 (1.17-4.44, P = 0.016) as well as non-CHD CVD cases 2.21 (1.17-4.19, P = 0.015) when comparing girls with PHV after versus prior to age 12. Timing of PHV was not associated with traditional CVD risk factors in mid life including body mass index and adverse lipid profiles or with all-cause mortality. DISCUSSION: Earlier timing of PHV in girls may increase the lifetime risk of CVD mortality and may be an important determinant for later cardiovascular health. PMID- 24219757 TI - The roles of some scorpions, Hemiscorpius lepturus and Androctonus crassicauda, in a scorpionism focus in Ramhormorz, southwestern Iran. AB - Scorpion stings are a common and important health problem in Iran, particularly in south and southwestern Iran, including the province of Khuzestan. In the area of Khuzestan near the city of Ramhormoz, Hemiscorpius lepturus (Scorpionida: Hemiscorpioiidae) and Androctonus crassicauda (Buthidae) are present. Ramhormoz is in southwestern Iran and is one of the most important foci of the scorpion sting problem. The current study was carried out to gain both epidemiological and medical information about scorpion stings in and around the city of Ramhormoz. In total, 179 people who were admitted to the Emergency Department of Ramhormoz Imam Khomeini Hospital during 2008 and 2009 after being stung by scorpions were monitored. Epidemiological and medical parameters including sex of the victim; the part of the body stung; the month when stung; the biochemical parameters comprising blood sugar (BS), blood urea nitrogen (BUN), and creatinine (CR); hematological parameters including white blood cells (WBC), count blood cells (CBC), red blood cells (RBC), hemoglobin (Hb), hematocrit (HCT), platelet (PLT); and urine analysis including hemoglobinuria were recorded. The current study showed that most of the victims were stung by H. lepturus, while very few were stung by A. crassicaud, but in over half of the cases the species was not known. Stings were most common from May to Aguust. 73% of the victims were female. The limbs were the part of the body most likely to be stung. Hemogobinuria was very common in H. lepturus victims. PMID- 24219759 TI - An ecogenomic analysis of herbivore-induced plant volatiles in Brassica juncea. AB - Upon herbivore feeding, plants emit complex bouquets of induced volatiles that may repel insect herbivores as well as attract parasitoids or predators. Due to differences in the temporal dynamics of individual components, the composition of the herbivore-induced plant volatile (HIPV) blend changes with time. Consequently, the response of insects associated with plants is not constant either. Using Brassica juncea as the model plant and generalist Spodoptera spp. larvae as the inducing herbivore, we investigated herbivore and parasitoid preference as well as the molecular mechanisms behind the temporal dynamics in HIPV emissions at 24, 48 and 72 h after damage. In choice tests, Spodoptera litura moth preferred undamaged plants, whereas its parasitoid Cotesia marginiventris favoured plants induced for 48 h. In contrast, the specialist Plutella xylostella and its parasitoid C. vestalis preferred plants induced for 72 h. These preferences matched the dynamic changes in HIPV blends over time. Gene expression analysis suggested that the induced response after Spodoptera feeding is mainly controlled by the jasmonic acid pathway in both damaged and systemic leaves. Several genes involved in sulphide and green leaf volatile synthesis were clearly up-regulated. This study thus shows that HIPV blends vary considerably over a short period of time, and these changes are actively regulated at the gene expression level. Moreover, temporal changes in HIPVs elicit differential preferences of herbivores and their natural enemies. We argue that the temporal dynamics of HIPVs may play a key role in shaping the response of insects associated with plants. PMID- 24219758 TI - The PICO project: aquatic exercise for knee osteoarthritis in overweight and obese individuals. AB - BACKGROUND: Aquatic exercise is recommended by the Osteoarthritis Research Society (OARSI), by the American College of Rheumatology (ACR) and by the European League Against Rheumatism (EULAR) as a nonpharmacological method of controlling the knee osteoarthritis (KOA) symptoms. Moreover, given that weight loss results in a reduction of the load that is exerted upon the knee during daily activities, obesity is also considered to be a modifiable risk factor for the development and or exacerbation of KOA. The implementation of an exercise based weight loss program may, however, itself be limited by the symptoms of KOA. The aquatic program against osteoarthritis (termed "PICO" in Portuguese) prioritizes the control of symptoms and the recovery of functionality, with an attendant increase in the patient's physical activity level and, consequently, metabolic rate. Our laboratory is assessing the effectiveness of 3 months of PICO on the symptoms of KOA, on physical function, on quality of life and on gait. In addition, PICO shall examine the effects of said exercise intervention on inflammatory biomarkers, psychological health, life style and body composition. METHODS/DESIGN: The trial is a prospective, single-blinded, randomized controlled trial, and involves 50 overweight and obese adults (BMI = 28-43.5 kg/m2; age 40 65 yrs) with radiographic KOA. The participants are randomly allocated into either an educational attention (control) group or an aquatic (exercise program) group. This paper describes the experimental protocol that is used in the PICO project. DISCUSSION: The PICO program shall provide insight into the effectiveness of an aquatic exercise program in the control of KOA symptoms and in the improvement of the quality of life. As such, they are likely to prove a useful reference to health professionals who intend to implement any kind of therapeutic intervention based around aquatic exercise. TRIAL REGISTRATION: NCT01832545. PMID- 24219761 TI - Thermodynamic basis for engineering high-affinity, high-specificity binding induced DNA clamp nanoswitches. AB - Naturally occurring chemoreceptors almost invariably employ structure-switching mechanisms, an observation that has inspired the use of biomolecular switches in a wide range of artificial technologies in the areas of diagnostics, imaging, and synthetic biology. In one mechanism for generating such behavior, clamp-based switching, binding occurs via the clamplike embrace of two recognition elements onto a single target molecule. In addition to coupling recognition with a large conformational change, this mechanism offers a second advantage: it improves both affinity and specificity simultaneously. To explore the physics of such switches we have dissected here the thermodynamics of a clamp-switch that recognizes a target DNA sequence through both Watson-Crick base pairing and triplex-forming Hoogsteen interactions. When compared to the equivalent linear DNA probe (which relies solely on Watson-Crick interactions), the extra Hoogsteen interactions in the DNA clamp-switch increase the probe's affinity for its target by ~0.29 +/- 0.02 kcal/mol/base. The Hoogsteen interactions of the clamp-switch likewise provide an additional specificity check that increases the discrimination efficiency toward a single-base mismatch by 1.2 +/- 0.2 kcal/mol. This, in turn, leads to a 10-fold improvement in the width of the "specificity window" of this probe relative to that of the equivalent linear probe. Given these attributes, clamp-switches should be of utility not only for sensing applications but also, in the specific field of DNA nanotechnology, for applications calling for a better control over the building of nanostructures and nanomachines. PMID- 24219762 TI - Thalidomide-induced angiopoietin 2, Notch1 and Dll4 downregulation under hypoxic condition in tissues with gastrointestinal vascular malformation and human umbilical vein endothelial cells. AB - OBJECTIVE: To determine the pathogenesis of gastrointestinal vascular malformation (GIVM) and the mechanism of thalidomide in treating GIVM by evaluating the expression of angiopoietin 2 (Ang2), Notch1, delta-like ligand 4 (Dll4) and hypoxia inducible factor 1alpha (Hif-1alpha). METHODS: Data of 10 patients with histology-confirmed GIVM were reviewed. Immunohistochemistry of surgically resected GIVM tissues and the adjacent mucosa of the patients and normal tissues from those who had undergone colonoscopy for health examination was performed to examine the expressions of Ang2, Notch1, Dll4 and Hif-1alpha. In addition, in vitro effect of thalidomide on Ang2, Notch1 and Dll4 in human umbilical vein endothelial cells (HUVEC) and on HUVEC proliferation was also investigated during normoxic and hypoxic conditions. RESULTS: GIVM lesions presented as tortuous, dilated arterioles, venules and capillaries. Ang2, Notch1 and Dll4 showed strong immunoreactivity in the cytoplasm and nuclei of GIVM lesions but negative or weak positivity in the intestinal mucosa of the adjacent tissues and normal mucosa. Under hypoxic condition the expressions of Hif-1alpha, Ang2, Notch1 and Dll4 were upregulated and the tube formation was more abundant with a greater diameter of tubes. Moreover, thalidomide downregulated their expression in HUVEC and HUVEC proliferation decreased in a concentration dependent manner under both hypoxic and normoxic conditions. CONCLUSION: Ang2, Notch1, Dll4 and Hif-1alpha may play an important role in the pathogenesis of GIVM and may be potential targets of thalidomide in the treatment of the disease. PMID- 24219763 TI - Novel extended release budesonide formulation for treatment of ulcerative colitis. AB - INTRODUCTION: Budesonide , a synthetic, non-halogenated corticosteroid, has been introduced in the topical treatment of ulcerative colitis (UC). Budesonide MMX, a novel, once-daily oral formulation of budesonide that uses a multi-matrix system (MMX) technology to extend the release of budesonide throughout the colon proved to be effective for the treatment of active UC. The focus of this review is the current status of budesonide MMX in extensive and left-sided UC. AREAS COVERED: This paper covers the recent studies of budesonide MMX to describe its efficacy and safety in the treatment of mild-to-moderately active left-sided UC. A literature search and review of budesonide MMX were carried out using the PubMed database up to August 2013. EXPERT OPINION: Clinical studies of budesonide MMX in adults with mild-to-moderately active UC demonstrated its efficacy and tolerability in achieving clinical and endoscopic remission. Although one trial is still ongoing, budesonide MMX 9 mg tablets represented the first orally administered topical corticosteroid formulation targeting the entire colon for the management of patients with active, mild-to-moderate UC. PMID- 24219765 TI - Adsorption of Pd, Pt, Cu, Ag, and Au monomers on NiAl(110) surface: a comparative study from DFT calculations. AB - First principles calculations based on periodic density functional theory (DFT) have been used to investigate the structural, energetic and electronic properties of different transition metal atoms (Pd, Pt, Cu, Ag, and Au) on the NiAl(110) surface at low coverages (0.08 and 0.25 monolayer). All adatoms prefer to adsorb on 4-fold coordinated sites interacting with two Al and two Ni atoms and forming polar and covalent bonds, respectively. The calculated negative work function changes are explained by the effect of positive surface image created after adsorption, which induces the polarization of the negatively charged adsorbates. Consequently, for metals with similar electronegativity as Ni (Ag and Cu), this polarization effect becomes more significant and leads to larger negative work function changes, but the charge transferred is small. PMID- 24219764 TI - Rituximab-induced interleukin-15 reduction associated with clinical improvement in rheumatoid arthritis. AB - Rituximab therapy alters all aspects of B-cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin-15 (IL-15) along with the frequency of IL-15-related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin-15 trans presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin-15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL-15 (138 +/- 21 pg/ml at baseline, 48 +/- 18 pg/ml after third cycle, P = 0.03) along with IL-17 (1197 +/- 203 pg/ml at baseline, 623 +/- 213 pg/ml after third cycle, P = 0.03) and tended to increase the frequency of circulating regulatory T cells (3.1 +/- 1 cells/MUl at baseline, 7.7 +/- 2 cells/MUl after third cycle). Rituximab also significantly decreased IL-15 trans-presentation on surface monocytes of patients negative for IL-15 serum (mean fluorescence intensity: 4.82 +/- 1.30 at baseline, 1.42 +/- 0.69 after third cycle P = 0.05). Reduction of serum IL-15 was associated with decrease in CD8(+) CD45RO(+) /RA(+) ratio (1.17 +/- 0.21 at baseline, 0.36 +/- 0.06 at third cycle, P = 0.02). DAS28, erythrocyte sedimentation rate and C-reactive protein correlated significantly with CD8(+) CD45RO(+) /RA(+) ratio (R = 0.323, R = 0.357, R = 0.369 respectively, P < 0.001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL-15/memory T cell-related mechanisms beyond circulating B cells. PMID- 24219766 TI - Novel chemistry for the selective oxidation of benzyl alcohol by graphene oxide and N-doped graphene. AB - A novel mechanism for the selective activation of benzyl alcohol by graphene oxide and N-doped graphene has been proposed using density functional theory based calculations. Interestingly, the proposed mechanism opens new avenues for graphene and its derivative-based catalysis. PMID- 24219768 TI - Comparative impact of professional mental health background on ratings of consumer outcome and fidelity in an Illness Management and Recovery program. AB - OBJECTIVE: Illness Management and Recovery (IMR) is a widely used evidence-based standardized psychosocial intervention. Little is known, however, about the impact of practitioner professional background on the consumer outcome. The current study aims to examine the delivery impact of practitioners who were mental health professionals, peer providers, or paraprofessionals on fidelity and consumer outcome in IMR. METHOD: Study participants were 252 persons with serious mental illness receiving psychiatric rehabilitation services in the community who received IMR (n = 210) or treatment as usual (TAU; n = 42). Study participants completed IMR groups that were delivered by either mental health professionals (n = 126), peer providers (n = 43), or paraprofessionals (n = 41). Study participants in the treatment group completed the Illness Management and Recovery scale before starting and after completing the IMR program; participants in the control group completed the same scale twice in similar time intervals. Fidelity ratings were made. RESULTS: Regardless of practitioner background, consumers who received the IMR intervention demonstrated significant improvement compared to the control group. Post hoc analyses showed no statistically significant difference on consumer outcome regardless of whether the practitioner was a professional, paraprofessional, or a peer provider. All three IMR groups had good fidelity scores. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The results demonstrate that IMR can be implemented with good fidelity and generate positive outcomes when delivered by practitioners who receive sufficient training and supervision regardless of their professional background. PMID- 24219767 TI - Mediation analysis of critical time intervention for persons living with serious mental illnesses: assessing the role of family relations in reducing psychiatric rehospitalization. AB - OBJECTIVE: Critical Time Intervention (CTI) is a time-limited care coordination intervention designed to reduce homelessness and other adverse outcomes for persons living with serious mental illness during the transition period between institutions and community living. This study assesses whether CTI improves the quality of family relationships between family members and individuals living with serious mental illness, and examines whether changes in quality of family relationship mediated the association between the intervention and psychiatric rehospitalization outcomes. METHOD: This study utilizes data from a randomized controlled trial that assessed the effect of CTI in preventing homelessness. Following discharge from inpatient psychiatric treatment in New York City, 150 previously homeless persons living with serious mental illness were randomly assigned to receive usual services only or 9 months of CTI in addition to usual services. RESULTS: Findings from mixed-effects regression models indicated that those assigned to the CTI group reported greater frequency of family contact and greater improvement in satisfaction with family relations than the comparison group during the 18-month follow-up period. Mediation analysis revealed that greater improvement in satisfaction with family relations mediated the effect of CTI on psychiatric rehospitalization outcome, but only at a modest level. CONCLUSION AND IMPLICATIONS FOR PRACTICE: These findings suggest that a relatively brief but targeted intervention delivered at the point of hospital discharge may contribute to strengthening family relations and that improvement in perceived family relationship quality can contribute to a reduction in psychiatric rehospitalization. PMID- 24219769 TI - Activating older adults with serious mental illness for collaborative primary care visits. AB - OBJECTIVE: Persons with serious mental illness frequently receive inadequate medical care and are more likely to experience difficulty navigating the health care system compared with the general population. To address this gap in quality, we developed a program of peer co-led collaborative activation training for primary care (CAT-PC) designed to improve "patient activation" and person centered care in primary care visits for middle-aged and older adults with serious mental illness and cardiovascular risk. This report presents pilot study feasibility and participant outcomes for CAT-PC. METHOD: A pre-post pilot evaluation of CAT-PC included N = 17 adults (age >= 50) with serious mental illness and cardiovascular health risk conditions, and N = 6 primary care providers. CAT-PC consists of 9 weekly peer co-led patient education and skills training sessions and a 45-min video-based training for primary care providers. Pre-post measures included the Patient Activation Measure (PAM), Perceived Efficacy in Patient-Physician Interactions (PEPPI), Autonomy Preference Index (API) for preferred role in primary care encounters, and Social Skills Performance Assessment (SSPA) role-play test for medical visits. RESULTS: All 17 participants attended 5 or more sessions. Post-intervention improvement was found for patient activation and simulated performance of medical visit communication skills. Trends were observed for improved self-efficacy in provider interactions and greater preference for a more collaborative role in decision-making. CONCLUSIONS AND IMPLICATIONS: CAT-PC is a brief, peer co-led education and skills training intervention potentially improving patient activation in primary care encounters and providing an important missing component in emerging models of "patient-centered behavioral health homes" for this high-risk group. PMID- 24219770 TI - The acceptability and outcomes of a peer- and health-professional-led Stanford self-management program for Vietnam veterans with alcohol misuse and their partners. AB - OBJECTIVE: The purpose of this study was to determine the acceptability of peer- and health-professional-led self-management education using the Stanford Program with Australian veterans and their partners. METHODS: The 6-week program taught problem-solving and decision-making skills to activate healthful behaviors, including action-planning and goal-setting. The evaluation included a participant and facilitator postprogram questionnaire; group interview; and alcohol, posttraumatic stress disorder, anxiety, depression, anger, relationship, and quality-of-life measures as part of a randomized controlled study. RESULTS: Participants included 25 male veterans with comorbid alcohol dependency, psychiatric and medical conditions, and 18 female partners (n = 43), 61.5% of who reported a chronic condition. The primary outcome was a self-reported improvement in self-management of their conditions in 69% of participants, with another 22.2% reporting that their confidence to self-manage had improved. There was an improvement in all measures at 9 months. CONCLUSIONS: The program resulted in improvements in lifestyle and confidence in self-management for Vietnam veterans, a cohort difficult to engage in healthy behaviors. Most participants were also accompanied by their partners. The program is a valuable resource for providing self-management education to veterans with alcohol dependency and various chronic conditions and needs to be considered in the suite of rehabilitation programs available to Defense Force personnel, veterans, and their partners. PMID- 24219773 TI - Redox properties of structural Fe in clay minerals: 3. Relationships between smectite redox and structural properties. AB - Structural Fe in clay minerals is an important redox-active species in many pristine and contaminated environments as well as in engineered systems. Understanding the extent and kinetics of redox reactions involving Fe-bearing clay minerals has been challenging due to the inability to relate structural Fe(2+)/Fe(total) fractions to fundamental redox properties, such as reduction potentials (EH). Here, we overcame this challenge by using mediated electrochemical reduction (MER) and oxidation (MEO) to characterize the fraction of redox-active structural Fe (Fe(2+)/Fe(total)) in smectites over a wide range of applied EH-values (-0.6 V to +0.6 V). We examined Fe(2+)/Fe(total )- EH relationships of four natural Fe-bearing smectites (SWy-2, SWa-1, NAu-1, NAu-2) in their native, reduced, and reoxidized states and compared our measurements with spectroscopic observations and a suite of mineralogical properties. All smectites exhibited unique Fe(2+)/Fe(total) - EH relationships, were redox active over wide EH ranges, and underwent irreversible electron transfer induced structural changes that were observable with X-ray absorption spectroscopy. Variations among the smectite Fe(2+)/Fe(total) - EH relationships correlated well with both bulk and molecular-scale properties, including Fe(total) content, layer charge, and quadrupole splitting values, suggesting that multiple structural parameters determined the redox properties of smectites. The Fe(2+)/Fe(total) - EH relationships developed for these four commonly studied clay minerals may be applied to future studies interested in relating the extent of structural Fe reduction or oxidation to EH-values. PMID- 24219772 TI - Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers. AB - This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H: quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Logistic regression was used to analyze data from a multicenter case-control study and estimate adjusted odds ratio (OR) and 95% confidence interval (CI). Exposure to pesticides was associated with increased bladder cancer risk (odds ratio (95% confidence interval): 1.68 (1.23-2.29)) in a dose dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism. PMID- 24219774 TI - Axial strength test for round flat faced versus capsule shaped bilayer tablets. AB - There has been increasing interest in fixed dose combination (FDC) therapy. Multi layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage. PMID- 24219775 TI - Thrombin generation as marker to estimate thrombosis risk in patients with abnormal test results in lupus anticoagulant routine diagnostics. AB - BACKGROUND: Lupus anticoagulant (LA) is known to inhibit thrombin generation although patients have an increased risk to develop thrombosis. We tried to determine whether thrombin generation is altered in plasma samples of patients with abnormal test results in LA routine diagnostics and whether its measurement may improve the risk assessment of thrombosis. METHODS: Samples from 63 patients (39 with abnormal test results; 24 controls) were included in the study. Measurement of diluted Russel's viper venom time (dRVVT) was part of the initial guideline conform diagnostic procedure for detection of LA. In addition, measurement of anticardiolipin-IgM, -IgG and beta2-glycoprotein-I-IgM, -IgG were performed. Thrombin generation was measured using two different phospholipid concentrations in the starting reagent. RESULTS: Analyzing all samples by logistic regression, thrombin generation after induction with high phospholipid concentrations was the best predictor of thrombosis. After preselection of samples with alterations in dRVVT, specificity of selected thrombin generation derived parameters for the detection of previous thrombosis increased in this subgroup. CONCLUSIONS: In patients with phospholipid-dependent prolongation of dRVVT, thrombin generation is variably inhibited and the degree of inhibition corresponds to the occurrence of previous thrombosis. Measuring thrombin generation in patients with phospholipid-dependent dRVVT prolongation may improve risk assessment of thrombosis. PMID- 24219776 TI - Automatic amygdala response to facial expression in schizophrenia: initial hyperresponsivity followed by hyporesponsivity. AB - BACKGROUND: It is well established that the amygdala is crucially involved in the processing of facial emotions. In schizophrenia patients, a number of neuroimaging findings suggest hypoactivation of the amygdala in response to facial emotion, while others indicate normal or enhanced recruitment of this region. Some of this variability may be related to the baseline condition used and the length of the experiment. There is evidence that schizophrenia patients display increased activation of the amygdala to neutral faces and that this is predominantly observed during early parts of the experiment. Recent research examining the automatic processing of facial emotion has also reported amygdala hyperactivation in schizophrenia. In the present study, we focused on the time course of amygdala activation during the automatic processing of emotional facial expression. We hypothesized that in comparison to healthy subjects, patients would initially show hyperresponsivity of the amygdala to masked emotional and neutral faces. In addition, we expected amygdala deactivation in response to masked facial emotions from the first to the second phase to be more pronounced in patients than in controls. RESULTS: Amygdala activation in response to angry, happy, neutral, and no facial expression (presented for 33 ms) was measured by functional magnetic resonance imaging in 30 schizophrenia patients and 35 healthy controls. Across all subjects, the bilateral amygdala response to faces (relative to the no facial expression condition) was larger in the initial phase (first half of trials) than in the second phase (second half of trials). During the initial phase, schizophrenia patients exhibited an increased right amygdala response to all faces and an increased left amygdala response to neutral faces compared with controls. During the second phase, controls manifested a higher right amygdala response for all faces and a higher left amygdala response to angry faces than patients. CONCLUSIONS: Schizophrenia patients are characterized by high initial amygdala responsivity to facial expressions at an automatic processing level, which substantially decreases with time. Amygdala deactivation over time might reflect an automatic mechanism by which schizophrenia patients suppress the processing of facial stimuli. This blocking mechanism could help patients avoid overstimulation during social interactions. PMID- 24219777 TI - A critical review of glove and hand research with regard to medical glove design. AB - Research from a number of areas was surveyed, including hand function; skin friction; manual performance testing; glove comfort, fit and durability; and user perception. The relevance of the research to medical glove design was discussed. It was concluded that, while an understanding has been gained of the factors that affect glove performance in general, specific application to thin rubber gloves has not been well explored. The focus in glove performance testing has also been on simple tasks such as pegboards, which do not necessarily assess the fine dexterity required in many surgical tasks. Recommendations were made for the development of a new battery of tests specific to medical gloves that would simulate real medical tasks and could produce repeatable results and have sufficient resolution to differentiate between glove types. PMID- 24219778 TI - Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis. AB - The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug design and a pseudo ring replacement strategy. The cocrystal structure of Mer with two compounds (7 and 22) possessing distinct activity have been determined. Subsequent SAR studies identified compound 23 (UNC2881) as a lead compound for in vivo evaluation. When applied to live cells, 23 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with 23 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, 23 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis. PMID- 24219779 TI - Phenotypical and molecular responses of Arabidopsis thaliana roots as a result of inoculation with the auxin-producing bacterium Azospirillum brasilense. AB - The auxin-producing bacterium Azospirillum brasilense Sp245 can promote the growth of several plant species. The model plant Arabidopsis thaliana was chosen as host plant to gain an insight into the molecular mechanisms that govern this interaction. The determination of differential gene expression in Arabidopsis roots after inoculation with either A. brasilense wild-type or an auxin biosynthesis mutant was achieved by microarray analysis. Arabidopsis thaliana inoculation with A. brasilense wild-type increases the number of lateral roots and root hairs, and elevates the internal auxin concentration in the plant. The A. thaliana root transcriptome undergoes extensive changes on A. brasilense inoculation, and the effects are more pronounced at later time points. The wild type bacterial strain induces changes in hormone- and defense-related genes, as well as in plant cell wall-related genes. The A. brasilense mutant, however, does not elicit these transcriptional changes to the same extent. There are qualitative and quantitative differences between A. thaliana responses to the wild-type A. brasilense strain and the auxin biosynthesis mutant strain, based on both phenotypic and transcriptomic data. This illustrates the major role played by auxin in the Azospirillum-Arabidopsis interaction, and possibly also in other bacterium-plant interactions. PMID- 24219780 TI - Tasks and strategies of self-management of living with antiretroviral therapy in Uganda. AB - There is increasing interest in promoting and supporting self-management of HIV and antiretroviral treatment (ART), including in resource-limited settings. Although the impact of HIV and ART on people in Uganda has been explored, little attention has been paid to how people self-manage. This qualitative study collected data from 20 participants on ART in Wakiso district, Uganda, using in depth interviews, life histories, and observations to explore the tasks and strategies of living with ART. The identified strategies were compared to two existing self-management frameworks. Results highlighted a range of tasks including obtaining, taking, and adhering to ART medication, monitoring their condition, living with stigma and managing disclosure, maintaining general health, and adjusting to new roles. Participants described a range of strategies or behaviors to manage, which they actively created and used, tailored to their needs and environment. Comparison with existing frameworks revealed many similarities, with some local differences in enactment, and greater emphasis in our sample on obtaining the medication. Interventions to support people with self management in Uganda, and possibly other resource-limited settings, require careful adaptation to local settings. The degree to which each of these strategies may improve health and quality of life requires further investigation. PMID- 24219781 TI - Inhibition of alpha-glucosidase and glucose intestinal absorption by Thymelaea hirsuta fractions. AB - BACKGROUND: Thymelaea hirsuta (L.) Endl. (Thymelaeaceae) is a medicinal plant used in Morocco to treat diabetes. In previous studies T. hirsuta has shown a potent antihyperglycemic effect. Our aim was to study the effect of the plant on alpha-glucosidase inhibition and intestinal glucose absorption. METHODS: Five fractions of T. hirsuta were tested, in vitro, in vivo and, in situ, to elucidate the inhibition of alpha-glucosidase and intestinal glucose uptake. RESULTS: The fractions induced, in vitro, a significant inhibition of alpha-glucosidase. The ethyl acetate fraction (EATh) had high activity and its inhibition mode was non competitive. The EATh at 50 and 100 mg/kg doses, decreased significantly, in vivo, the postprandial hyperglycemia after sucrose loading in normal and diabetic mice. Moreover, 50 mg/kg of EATh significantly decreased intestinal glucose uptake, in situ, in rats. CONCLUSION: The antihyperglycemic effect of T. hirsuta can be explained, in part, by the inhibition of intestinal alpha-glucosidase and intestinal glucose absorption. PMID- 24219782 TI - Association of cardiopulmonary resuscitation psychomotor skills with knowledge and self-efficacy in nursing students. AB - Effective cardiopulmonary resuscitation (CPR) skills are essential for better patient survival, but whether these skills are associated with knowledge of and self-efficacy in CPR is not well known. The purpose of this study was to assess the quality of CPR skills and identify the association of the psychomotor skills with knowledge and self-efficacy at the time of CPR skills training. A convenience sample of 124 nursing students participated in a one-group posttest only study. The quality of CPR psychomotor skills, as assessed by structured observation using a manikin, was suboptimal. Nursing students who performed correct chest compression skills reported higher self-efficacy, but there was no association between CPR psychomotor skills and total knowledge. Rigorous skills training sessions with more objective feedback on performance and individual coaching are warranted to enable mastery learning and self-efficacy. PMID- 24219783 TI - Value stability and change during self-chosen life transitions: self-selection versus socialization effects. AB - Three longitudinal studies examine a fundamental question regarding adjustment of personal values to self-chosen life transitions: Do values fit the new life setting already at its onset, implying value-based self-selection? Or do values change to better fit the appropriate and desirable values in the setting, implying value socialization? As people are likely to choose a life transition partly based on their values, their values may fit the new life situation already at its onset, leaving little need for value socialization. However, we propose that this may vary as a function of the extent of change the life transition entails, with greater change requiring more value socialization. To enable generalization, we used 3 longitudinal studies spanning 3 different life transitions and different extents of life changes: vocational training (of new police recruits), education (psychology vs. business students), and migration (from Poland to Britain). Although each life transition involved different key values and different populations, across all 3 studies we found value fit to the life situation already early in the transition. Value socialization became more evident the more aspects of life changed as part of the transition, that is, in the migration transition. The discussion focuses on the implications of these findings for research on values and personality change, as well as limitations and future directions for research. PMID- 24219784 TI - Unconscious processes improve lie detection. AB - The capacity to identify cheaters is essential for maintaining balanced social relationships, yet humans have been shown to be generally poor deception detectors. In fact, a plethora of empirical findings holds that individuals are only slightly better than chance when discerning lies from truths. Here, we report 5 experiments showing that judges' ability to detect deception greatly increases after periods of unconscious processing. Specifically, judges who were kept from consciously deliberating outperformed judges who were encouraged to do so or who made a decision immediately; moreover, unconscious thinkers' detection accuracy was significantly above chance level. The reported experiments further show that this improvement comes about because unconscious thinking processes allow for integrating the particularly rich information basis necessary for accurate lie detection. These findings suggest that the human mind is not unfit to distinguish between truth and deception but that this ability resides in previously overlooked processes. PMID- 24219785 TI - The impact bias is alive and well. AB - A substantial body of research on affective forecasting has found that people often overestimate the affective impact of future events. Levine, Lench, Kaplan, and Safer (2012) argued that whereas people may overestimate the duration of their emotional responses, they do not overestimate the initial intensity of these responses as much as previous research has suggested. We suggest that Levine et al. (a) failed to review or include in their meta-analysis many studies that directly contradict their claim, (b) used a faulty classification scheme, (c) collapsed across conditions that were meant to (and did) produce opposing effects, and (d) miscoded some of the studies they did include. When these errors are corrected, their claim is clearly not supported. Levine et al. also reported the results of 4 studies, which are open to alternative explanations. The impact bias is alive and well. PMID- 24219786 TI - Like Schrodinger's cat, the impact bias is both dead and alive: reply to Wilson and Gilbert (2013). AB - In their comment on our article on affective forecasting (Levine, Lench, Kaplan, & Safer, 2012), Wilson and Gilbert (2013) criticized the meta-analysis, proposed alternative explanations for the empirical studies, and concluded that the impact bias is alive and well. Our reply demonstrates that, irrespective of the exclusion of effects and selective recoding of effects recommended for the meta analysis, the pattern of results remains the same: Study participants' forecasts are more accurate when they report their feelings about a focal event, or immediately after a focal event, than when they report their feelings in general after a delay. New analyses rule out individual differences and focalism as alternative explanations for the results of our empirical studies. These studies show that people can accurately predict the intensity of their feelings about events. People overestimate in predicting the impact of events on their emotional state in general, but clarifying the meaning of the forecasting question reduces the magnitude of this bias. We conclude that the impact bias, which encompasses overestimating the intensity of feelings about events and overestimating the intensity of feelings in general, is both dead and alive. The importance of predicting feelings about events for decision making and the reasons people predict some features of emotion more accurately than others are discussed. PMID- 24219788 TI - Effects of five metals on the evolution of hydrogen sulfide, methanethiol, and dimethyl sulfide during anaerobic storage of Chardonnay and Shiraz wines. AB - The synergistic effects of Cu, Fe, Mn, Zn, and Al on the evolution of different volatile sulfur compounds (VSCs) in a Chardonnay and a Shiraz wine have been investigated. The evolution of H2S, MeSH, and DMS were influenced by metal addition, and in some instances, a combination of metals was responsible for the largest variation in the concentration of VSCs. The metals and metal combinations associated with significant changes in VSC concentrations in both Chardonnay and Shiraz samples after anaerobic storage were Cu, Fe, Zn, Al, Cu*Fe, Cu*Mn*Al, and Cu*Zn*Al for H2S; Cu, Zn, Fe*Mn, and Cu*Fe*Mn for MeSH; and Al and Zn*Al for DMS. The effect of Cu addition on the evolution of VSCs has previously been shown; however, this investigation has demonstrated that metals other than Cu could also be involved in the catalytic release of VSCs and that the interactions and combinations of metals are important. In some instances, the metal effect was reversed, associated with significant decreases during high oxygen conditions and with significant increases during low oxygen conditions. PMID- 24219789 TI - Nanostructures and electronic properties of a high-efficiency electron-donating polymer. AB - The development of organic photovoltaic (OPV) solar cells has seeded a bright hope of achieving low-cost solar energy harvesting. Practical realization and successful commercialization require enhancing the efficiency of solar energy harvesting, which, in turn, relies on the core understanding of structure property relationships in OPV materials. Here, we report the first large-scale density functional calculations of the nanoconformational and electronic properties of the thieno[3,4-b]thiophene-alt-benzodithiophene copolymer (PTB7), a high-efficiency OPV material. These first-principles results include the chain length dependence of the torsional potential, the nearest-neighbor torsional coupling, the band gap, and the electronic conjugation length. Importantly, PTB7 was found to have a torsional potential almost independent of chain length, very weak nearest-neighbor torsional coupling, a low band gap (~1.8 eV), and a very long conjugation length (~147 A) compared to the other conjugated polymers like polythiophene and poly(3-alkylthiophene). These results suggest that PTB7 can be an efficient electron donor for OPV devices. PMID- 24219790 TI - Sustained frictional instabilities on nanodomed surfaces: stick-slip amplitude coefficient. AB - Understanding the frictional properties of nanostructured surfaces is important because of their increasing application in modern miniaturized devices. In this work, lateral force microscopy was used to study the frictional properties between an AFM nanotip and surfaces bearing well-defined nanodomes comprising densely packed prolate spheroids, of diameters ranging from tens to hundreds of nanometers. Our results show that the average lateral force varied linearly with applied load, as described by Amontons' first law of friction, although no direct correlation between the sample topographic properties and their measured friction coefficients was identified. Furthermore, all the nanodomed textures exhibited pronounced oscillations in the shear traces, similar to the classic stick-slip behavior, under all the shear velocities and load regimes studied. That is, the nanotextured topography led to sustained frictional instabilities, effectively with no contact frictional sliding. The amplitude of the stick-slip oscillations, sigmaf, was found to correlate with the topographic properties of the surfaces and scale linearly with the applied load. In line with the friction coefficient, we define the slope of this linear plot as the stick-slip amplitude coefficient (SSAC). We suggest that such stick-slip behaviors are characteristics of surfaces with nanotextures and that such local frictional instabilities have important implications to surface damage and wear. We thus propose that the shear characteristics of the nanodomed surfaces cannot be fully described by the framework of Amontons' laws of friction and that additional parameters (e.g., sigmaf and SSAC) are required, when their friction, lubrication, and wear properties are important considerations in related nanodevices. PMID- 24219791 TI - Schisandrin B attenuates acetaminophen-induced hepatic injury through heat-shock protein 27 and 70 in mice. AB - BACKGROUND AND AIM: Schisandrin B is an active component isolated from Schisandra chinensis (TurcZ.) Baill. that is widely used as an antihepatotoxic agent. Schisandrin B has significant hepatoprotective effect against chemical and immunological liver injury. This study aimed to investigate the effect of Schisandrin B on the expression of 27- and 70-kDa heat-shock protein (HSP) and its role in protection against acetaminophen-induced liver injury in mice. METHODS: After the mice were pretreated, Western blot and real-time quantitative polymerase chain reaction were used to detect the protein and gene expression of HSP27 and HSP70, respectively; the liver tissues were subjected to histological evaluation, and alanine aminotransferase and aspartate aminotransferase activities in the serum were measured. RESULTS: Oral administration of Schisandrin B increased the expression of HSP27 and HSP70 in a time- and dose dependent manner. The inducing effect of Schisandrin B on HSP27 and HSP70 was also confirmed by real-time quantitative polymerase chain reaction. In the acetaminophen-induced liver injury mouse model, the prior oral administration of Schisandrin B (200 mg/kg) three times in 24 h markedly alleviated liver injury as indicated by the amelioration of histopathological hepatic necrosis and the reduction of alanine aminotransferase and aspartate aminotransferase activities in the serum. However, the earlier actions of Schisandrin B were all suppressed significantly by Quercetin, a known HSP inhibitor. CONCLUSION: The hepatic cytoprotective action of Schisandrin B against acetaminophen-induced liver injury is mediated, at least in part, by the induction of HSP27 and HSP70 in mice. PMID- 24219792 TI - The endotoxin/toll-like receptor-4 axis mediates gut microvascular dysfunction associated with post-prandial lipidemia. AB - BACKGROUND: Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting. RESULTS: Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil. CONCLUSIONS: Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress. PMID- 24219793 TI - Pharmacotherapy of allergic rhinitis: current options and future perspectives. AB - INTRODUCTION: Allergic rhinitis (AR) is a very common disease, caused by environmental aeroallergen, and clinically expressed by sneezing, nasal itching, rhinorrhea and obstruction. It is often considered a mild illness, but actually it has a significant individual and social burden. The management of AR is based on allergen avoidance, pharmacological treatment and allergen specific immunotherapy. AREAS COVERED: In this article, the authors summarize the current status of pharmacotherapy of AR, its possible options and the future perspective. EXPERT OPINION: In most cases of AR, pharmacotherapy must be considered the cornerstone intervention. Particularly, antihistamines and intranasal corticosteroids should be the first-line agents. Other agents to be considered, depending on clinical features in single patients, are systemic corticosteroids, antileukotrienes, anticholinergics, nasal decongestants and mast cell stabilizers. Specific immunotherapy is able to reduce the drugs consumption and was shown to be effective in severe rhinitis uncontrolled with drugs. The future perspective include combination therapy with intranasal antihistamines and corticosteroids, the anti-IgE antibody omalizumab, histamine H3 and H4 receptor antagonists, cytokine inhibitors and toll-like receptors targeted treatment. PMID- 24219794 TI - Modular, gold-catalyzed approach to the synthesis of lead-like piperazine scaffolds. AB - Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Manipulation of the tetrahydropyrazines, by reduction or using multicomponent reactions, yielded piperazine scaffolds in which substitution of the carbon atoms was varied. Such scaffolds may have value in the synthesis of novel screening compounds with lead-like molecular properties. PMID- 24219796 TI - Cell-to-cell signaling through light: just a ghost of chance? AB - Despite the large number of reports attributing the signaling between detached cell cultures to the electromagnetic phenomena, almost no report so far included a rigorous analysis of the possibility of such signaling.In this paper, we examine the physical feasibility of the electromagnetic communication between cells, especially through light, with regard to the ambient noise illumination. We compare theoretically attainable parameters of communication with experimentally obtained data of the photon emission from cells without a specially pronounced ability of bioluminescence.We show that the weak intensity of the emission together with an unfavorable signal-to-noise ratio, which is typical for natural conditions, represent an important obstacle to the signal detection by cells. PMID- 24219797 TI - Solid-state stability and compatibility studies of clavulanate potassium. AB - The kinetic and thermodynamic parameters of degradation of clavulanate potassium in the solid state were studied by using a reversed phase high performance liquid chromatography (RP-HPLC) method. The degradation of clavulanate potassium was a first-order reaction depending on the substrate concentration at an increased relative air humidity (RH) and in dry air. The dependence ln k = f(1/T) became the ln k = (0.026 +/- 166.35)-(2702.82 +/- 1779.43)(1/T) in dry air and ln k = (1.65 +/- 100.40) * 10(3)-(5748.81 +/- 3659.67)(1/T) at 76.4% RH. The thermodynamic parameters Ea, DeltaH(?a), DeltaS(?a) of the degradation of clavulanate potassium in the solid state were calculated. The dependence ln k = f (RH%) assumed the form ln k = (8.78 +/- 5.75) 10 (-2) (RH%) + (2.64 * 10(-8 )+/- 40.41). The compatibility of clavulanate potassium with commonly used excipients was studied at an increased temperature and in dry air. The geometric structure of molecule, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were also determined in order to predict the structural changes and reactive sites in clavulanate potassium during degradation and compatibility studies in the solid state. The ultraviolet (UV), Fourier transform infrared spectroscopy (FT-IR) and Raman spectra of degraded samples of the compound were analyzed. PMID- 24219798 TI - Magnetic nanoparticle hyperthermia: a new frontier in biology and medicine? PMID- 24219799 TI - Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model. AB - PURPOSE: The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in a mouse mammary adenocarcinoma model. MATERIALS AND METHODS: A thermal dose equivalent to 60 min at 43 degrees C (CEM60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumour (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch-coated magnetic nanoparticles. Following mNP delivery, the mouse/tumour was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumour to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. RESULTS: Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p = 0.09) when prescribed to the same thermal dose. Tumours treated with mNPH also demonstrated reduced peritumoral normal tissue damage. CONCLUSIONS: Our results demonstrate similar tumour treatment efficacy when tumour heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumour hyperthermia. These results further indicate that this improvement is due to improved heat localisation in the tumour. PMID- 24219800 TI - In vivo applications of magnetic nanoparticle hyperthermia. AB - Hyperthermia is considered to be a promising tool for the treatment of tumours. Intensive research activities reveal a distinct impact not only on the cellular level but also on tumour physiology which favours the combination with the classical oncologic modalities radio- and chemotherapy. Different techniques have been established so far. Among them, magnetic hyperthermia exploits the intrinsic magnetic properties of iron oxide nanoparticles (magnetite and maghemite) which induce heating during the exposure to an alternating magnetic field. Beyond the advantage that heating is generated within the tumour and not from outside the body, the amounts of magnetic material and their intratumoral distribution patterns are key factors determining the therapeutic outcome. They can be influenced by the use of different application routes, which will be discussed in this paper. PMID- 24219802 TI - Which factors influence the appropriateness of testosterone-lowering medications for sex offenders? A survey among clinicians from German forensic-psychiatric institutions. AB - OBJECTIVES: Although testosterone-lowering medications (TLM) are a frequently used addition to psychotherapy in sex offender treatment, discord still seems to exist amongst clinicians as to in which cases administering TLM is justified. The depo-Provera scale (DPS), which was published by Maletzky and Field (Aggress Violent Behav 2003;8:391), assesses the appropriateness of TLM administration in sex offender treatment. METHODS: The DPS was sent to all forensic psychiatric institutions in Germany. The clinical directors of these institutions were asked to rate the importance of each item of the DPS on a six-point Likert scale. RESULTS: Twenty-nine clinicians participated. The most important reason selected for the prescription of TLM for sex offender treatment was a "history of sexual offender treatment failure". The least important item was "deviant sexual interest, by plethysmograph or Abel Screen" (neither plethysmograph nor Abel Screen is used in Germany). CONCLUSIONS: Clinicians' attitudes towards the DPS correspond to the suggestions made in the current WSFBF-guidelines for the pharmacological treatment of sex offenders (Thibaut et al. 2010 ; World J Biol Psychiatry 11:604-655). Use of the DPS could therefore contribute to a more structured approach towards helping clinicians come to a decision about whether or not to treat a sex offender with TLM. PMID- 24219803 TI - Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression. AB - OBJECTIVES. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). METHODS: DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. RESULTS: The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. CONCLUSIONS: We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system. PMID- 24219804 TI - Low serum BDNF levels in depressed patients cannot be attributed to individual depressive symptoms or symptom cluster. AB - OBJECTIVES: Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. METHODS: All 1070 patients with a past 6-month diagnosis of major depressive disorder from the Netherlands Study of Depression and Anxiety (NESDA) were included. Composite International Diagnostic Interview (CIDI) and Inventory of Depressive Symptoms (IDS) items were tested individually in separate multiple regression analyses with serum BDNF level as the dependent and the CIDI or IDS item as independent variable. Subsequently, we compared BDNF levels between patients with seasonal affective disorder (based on the Seasonal Pattern Assessment Questionnaire) and melancholic depression, atypical depression and moderate depression (based on a latent class analysis). All analyses were adjusted for confounders. RESULTS: Only one item was significantly associated with serum BDNF levels, namely the CIDI item "loss of interest" (beta = 0.14; P < 0.01). Counterintuitively the presence of this symptom was associated with higher BDNF levels. Other items and the comparison between different types of depression did not reveal significant differences. CONCLUSIONS: Decreased serum BDNF levels in depression cannot be attributed to a specific symptom or symptom cluster. PMID- 24219801 TI - Discovery of protective B-cell epitopes for development of antimicrobial vaccines and antibody therapeutics. AB - Protective antibodies play an essential role in immunity to infection by neutralizing microbes or their toxins and recruiting microbicidal effector functions. Identification of the protective B-cell epitopes, those parts of microbial antigens that contact the variable regions of the protective antibodies, can lead to development of antibody therapeutics, guide vaccine design, enable assessment of protective antibody responses in infected or vaccinated individuals, and uncover or localize pathogenic microbial functions that could be targeted by novel antimicrobials. Monoclonal antibodies are required to link in vivo or in vitro protective effects to specific epitopes and may be obtained from experimental animals or from humans, and their binding can be localized to specific regions of antigens by immunochemical assays. The epitopes are then identified with mapping methods such as X-ray crystallography of antigen-antibody complexes, antibody inhibition of hydrogen-deuterium exchange in the antigen, antibody-induced alteration of the nuclear magnetic resonance spectrum of the antigen, and experimentally validated computational docking of antigen-antibody complexes. The diversity in shape, size and structure of protective B-cell epitopes, and the increasing importance of protective B-cell epitope discovery to development of vaccines and antibody therapeutics are illustrated through examples from different microbe categories, with emphasis on epitopes targeted by broadly neutralizing antibodies to pathogens of high antigenic variation. Examples include the V-shaped Ab52 glycan epitope in the O antigen of Francisella tularensis, the concave CR6261 peptidic epitope in the haemagglutinin stem of influenza virus H1N1, and the convex/concave PG16 glycopeptidic epitope in the gp120 V1/V2 loop of HIV type 1. PMID- 24219805 TI - Schwann cell-free adult canine olfactory ensheathing cell preparations from olfactory bulb and mucosa display differential migratory and neurite growth promoting properties in vitro. AB - BACKGROUND: Transplantation of olfactory ensheathing cells (OEC) and Schwann cells (SC) is a promising therapeutic strategy to promote axonal growth and remyelination after spinal cord injury. Previous studies mainly focused on the rat model though results from primate and porcine models differed from those in the rat model. Interestingly, canine OECs show primate-like in vitro characteristics, such as absence of early senescence and abundance of stable p75NTR expression indicating that this species represents a valuable translational species for further studies. So far, few investigations have tested different glial cell types within the same study under identical conditions. This makes it very difficult to evaluate contradictory or confirmatory findings reported in various studies. Moreover, potential contamination of OEC preparations with Schwann cells was difficult to exclude. Thus, it remains rather controversial whether the different glial types display distinct cellular properties. RESULTS: Here, we established cultures of Schwann cell-free OECs from olfactory bulb (OB-OECs) and mucosa (OM-OECs) and compared them in assays to Schwann cells. These glial cultures were obtained from a canine large animal model and used for monitoring migration, phagocytosis and the effects on in vitro neurite growth. OB-OECs and Schwann cells migrated faster than OM-OECs in a scratch wound assay. Glial cell migration was not modulated by cGMP and cAMP signaling, but activating protein kinase C enhanced motility. All three glial cell types displayed phagocytic activity in a microbead assay. In co-cultures with of human model (NT2) neurons neurite growth was maximal on OB-OECs. CONCLUSIONS: These data provide evidence that OB- and OM-OECs display distinct migratory behavior and interaction with neurites. OB-OECs migrate faster and enhance neurite growth of human model neurons better than Schwann cells, suggesting distinct and inherent properties of these closely-related cell types. Future studies will have to address whether, and how, these cellular properties correlate with the in vivo behavior after transplantation. PMID- 24219806 TI - Aortic arch shape is not associated with hypertensive response to exercise in patients with repaired congenital heart diseases. AB - BACKGROUND: Aortic arch geometry is linked to abnormal blood pressure (BP) response to maximum exercise. This study aims to quantitatively assess whether aortic arch geometry plays a role in blood pressure (BP) response to exercise. METHODS: 60 age- and BSA-matched subjects--20 post-aortic coarctation (CoA) repair, 20 transposition of great arteries post arterial switch operation (ASO) and 20 healthy controls--had a three-dimensional (3D), whole heart magnetic resonance angiography (MRA) at 1.5 Tesla, 3D geometric reconstructions created from the MRA. All subjects underwent cardiopulmonary exercise test on the same day as MRA using an ergometer cycle with manual BP measurements. Geometric analysis and their correlation with BP at peak exercise were assessed. RESULTS: Arch curvature was similarly acute in both the post-CoA and ASO cases [0.05 +/- 0.01 vs. 0.05 +/- 0.01 (1/mm/m2); p = 1.0] and significantly different to that of normal healthy controls [0.05 +/- 0.01 vs. 0.03 +/- 0.01 (1/mm/m2), p < 0.001]. Indexed transverse arch cross sectional area were significantly abnormal in the post-CoA cases compared to the ASO cases (117.8 +/- 47.7 vs. 221.3 +/- 44.6; p < 0.001) and controls (117.8 +/- 47.7 vs. 157.5 +/- 27.2 mm2; p = 0.003). BP response to peak exercise did not correlate with arch curvature (r = 0.203, p = 0.120), but showed inverse correlation with indexed minimum cross sectional area of transverse arch and isthmus (r = -0.364, p = 0.004), and ratios of minimum arch area/ descending diameter (r = -0.491, p < 0.001). CONCLUSION: Transverse arch and isthmus hypoplasia, rather than acute arch angulation plays a role in the pathophysiology of BP response to peak exercise following CoA repair. PMID- 24219807 TI - Measurement of air-sea exchange of dimethyl sulfide and acetone by PTR-MS coupled with gradient flux technique. AB - We developed a new method for in situ measurement of air-sea fluxes of multiple volatile organic compounds (VOCs) by combining proton transfer reaction-mass spectrometry (PTR-MS) and gradient flux (GF) technique. The PTR-MS/GF system was first deployed to determine the air-sea flux of VOCs in the open ocean of the western Pacific, in addition to carbon dioxide and water vapor. Each profiling at seven heights from the ocean surface up to 14 m took 7 min. In total, 34 vertical profiles of VOCs in the marine atmosphere just above the ocean surface were obtained. The vertical gradient observed was significant for dimethyl sulfide (DMS) and acetone with the best-fit curves on quasi-logarithmic relationship. The mean fluxes of DMS and acetone were 5.5 +/- 1.5 and 2.7 +/- 1.3 MUmol/m(2)/day, respectively. These fluxes are in general in accordance with those reported by previous expeditions. PMID- 24219808 TI - Electrodeposited cobalt-sulfide catalyst for electrochemical and photoelectrochemical hydrogen generation from water. AB - A cobalt-sulfide (Co-S) film prepared via electrochemical deposition on conductive substrates is shown to behave as an efficient and robust catalyst for electrochemical and photoelectrochemical hydrogen generation from neutral pH water. Electrochemical experiments demonstrate that the film exhibits a low catalytic onset overpotential (eta) of 43 mV, a Tafel slope of 93 mV/dec, and near 100% Faradaic efficiency in pH 7 phosphate buffer. Catalytic current densities can approach 50 mA/cm(2) and activity is maintained for at least 40 h. The catalyst can also be electrochemically coated on silicon, rendering a water compatible photoelectrochemical system for hydrogen production under simulated 1 sun illumination. The facile preparation of this Co-S film, along with its low overpotential, high activity, and long-term aqueous stability, offer promising features for potential use in solar energy applications. PMID- 24219809 TI - Enmein-type 6,7-seco-ent-kauranoids from Isodon sculponeatus. AB - Fourteen enmein-type 6,7-seco-ent-kaurane diterpenoids, seven new ones (sculponins M-S, 1-7) and seven known compounds (8-14), were isolated from the aerial parts of Isodon sculponeatus . Compound 1 is the first example of an ent kauranoid, possessing a 11,12-epoxy group, and compounds 6 and 7 have a rare 3,6 epoxy group. The structures were established primarily by NMR and MS methods, and the absolute configurations of 1, 3, and 6 were determined by single-crystal X ray diffraction. Compound 14 showed significant cytotoxic activity against five human tumor lines, with IC50 values ranging from 1.0 to 3.5 MUM, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 2.2 MUM. PMID- 24219811 TI - Species and hybrid identification of sturgeon caviar: a new molecular approach to detect illegal trade. AB - Overexploitation of wild populations due to the high economic value of caviar has driven sturgeons to near extinction. The high prices commanded by caviar on world markets have made it a magnet for illegal and fraudulent caviar trade, often involving low-value farmed caviar being sold as top-quality caviar. We present a new molecular approach for the identification of pure sturgeon species and hybrids that are among the most commercialized species in Europe and North America. Our test is based on the discovery of species-specific single nucleotide polymorphisms (SNPs) in the ribosomal protein S7, supplemented with the Vimentin gene and the mitochondrial D-loop. Test validations performed in 702 specimens of target and nontarget sturgeon species demonstrated a 100% identification success for Acipenser naccarii, A. fulvescens, A. stellatus, A. sinensis and A. transmontanus. In addition to species identification, our approach allows the identification of Bester and AL hybrids, two of the most economically important hybrids in the world, with 80% and 100% success, respectively. Moreover, the approach has the potential to identify many other existing sturgeon hybrids. The development of a standardized sturgeon identification tool will directly benefit trade law enforcement, providing the tools to monitor and regulate the legal trade of caviar and protect sturgeon stocks from illicit producers and traders, hence contributing to safeguarding this group of heavily threatened species. PMID- 24219812 TI - Loss of melanocytes in hypopigmented mycosis fungoides: a study of 18 patients. AB - BACKGROUND: Hypopigmentation in hypopigmented mycosis fungoides (MF) is thought to result from the action of CD8+ cells on melanocytes. Here, we investigated the immunophenotype and melanocytic markers in hypopigmented MF lesions. METHODS: Specimens of hypopigmented lesions and normal skin from 18 patients with hypopigmented MF and specimens of non-hypopigmented lesions from 8 patients with classic/conventional MF were subjected to neoplastic immunophenotyping and melanocyte immunostaining with Melan-A, tyrosinase, stem cell factor receptor (CD117) and microphthalmia-associated transcription factor (MiTF). RESULTS: The CD8+ immunophenotype was more common in hypopigmented MF lesions (14/18) than in conventional MF lesions (1/8, p = 0.0033). There was a main effect of specimen type (hypopigmented MF lesion, hypopigmented MF normal skin, conventional MF lesion) on the number of melanocytes stained with Melan-A (median number/mm basal membrane, 1.97 vs. 4.77 vs. 5.42, respectively, p = 0.0046), tyrosinase (2.19 vs. 4.02 vs. 5.26, p = 0.0114), CD117 (4.29 vs. 7.81 vs. 5.45, p = 0.0064), and MiTF (2.75 vs. 4.43 vs. 4.98, p = 0.005). CONCLUSIONS: These results confirm previous findings of fewer melanocytes and CD117-positive melanocytes in hypopigmented MF and showed reduced MiTF identification, which is crucial for the function and survival of melanocytes. Thus cytotoxic CD8+ cell action may determine CD117/MiTF dysfunction, causing hypopigmentation. PMID- 24219813 TI - Person-centred care in the Indonesian health-care system. AB - Person-centred care (PCC) is defined as the health-care providers selecting and delivering interventions or treatments that are respectful of and responsive to the characteristics, needs, preferences and values of the individual person. This model of care puts the person at the centre of care delivery. The World Health Organization suggests that PCC is one of the essential dimensions of health care and as such is an important indicator of health-care quality. However, how PCC is implemented differs between countries in response to local cultures, resources and consumer expectations of health care. This article discusses person-centred care in the Indonesian health-care system. PMID- 24219815 TI - Effect of facial material softness and applied force on face mask dead volume, face mask seal, and inhaled corticosteroid delivery through an idealized infant replica. AB - BACKGROUND: During the aerosol delivery device design and optimization process, in vitro lung dose (LD) measurements are often performed using soft face models, which may provide a more clinically relevant representation of face mask dead volume (MDV) and face mask seal (FMS) than hard face models. However, a comparison of MDV, FMS, and LD for hard and soft face models is lacking. METHODS: Metal, silicone, and polyurethane represented hard, soft, and very soft facial materials, respectively. MDV was measured using a water displacement technique. FMS was measured using a valved holding chamber (VHC) flow rate technique. The LD of beclomethasone dipropionate (BDP) delivered via a 100-MUg Qvar(r) pressurized metered dose inhaler with AeroChamber Plus(r) Flow-Vu(r) VHC and Small Mask, defined as that which passes through the nasal airways of the idealized infant geometry, was measured using a bias tidal flow system with a filter. MDV, FMS, and LD were measured at 1.5 lb and 3.5 lb of applied force. A mathematical model was used to predict LD based on experimental measurements of MDV and FMS. RESULTS: Experimental BDP LD measurements for ABS, silicone, and polyurethane at 1.5 lb were 0.9 (0.6) MUg, 2.4 (1.9) MUg, and 19.3 (0.9) MUg, respectively. At 3.5 lb, the respective LD was 10.0 (1.5) MUg, 13.8 (1.4) MUg, and 14.2 (0.9) MUg. Parametric analysis with the mathematical model showed that differences in FMS between face models had a greater impact on LD than differences in MDV. CONCLUSIONS: The use of soft face models resulted in higher LD than hard face models, with a greater difference at 1.5 lb than at 3.5 lb. A lack of a FMS led to decreased dose consistency; therefore, a sealant should be used when measuring LD with a hard ABS or soft silicone face model at 1.5 lb of applied force or less. PMID- 24219814 TI - Nebulized tobramycin in the treatment of adult CF pulmonary exacerbations. AB - BACKGROUND: Repeated courses of intravenous (IV) aminoglycosides in cystic fibrosis (CF) patients are associated with cumulative nephrotoxicity. Targeting their delivery through the inhaled route during acute pulmonary exacerbations may also be effective, but without systemic side effects. METHODS: Using a randomized crossover trial design, in a pilot study we compared 14 days of IV tobramycin with nebulized tobramycin 300 mg twice a day (TNS) in acute respiratory exacerbations in 20 CF adults chronically infected with Pseudomonas aeruginosa (Psa). Patients also received IV colistin in both arms. RESULTS: Improvement in spirometry was similar between the two groups [mean change in FEV1 % predicted: IV group 16.4 (standard deviation 8.5) versus TNS group 19.9 (11.3), p=0.26], but there was more suppression of sputum Psa in the TNS group [mean difference between treatments 0.85 log10 colony-forming units/mL (CI 0.03 to 1.67), p=0.05]. IV tobramycin was associated with a greater urinary protein leak [mean difference between treatments 0.59 mg/24 hr (0.30 to 0.87), p=0.0005] and higher urinary levels of markers of acute renal tubular injury: N-acetylglucosaminidase [0.72 IU/mmol (0.37 to 1.07), p=0.0004], alanine aminopeptidase [1.19 IU/mmol (0.70 to 1.68), p=0.0001], and beta2-microglobulin [0.44 MUg/mmol (0.16 to 0.72), p=0.0046] than TNS. Compared with IV tobramycin, TNS treatment prolonged the time to next exacerbation requiring hospitalization (p<0.001). Patient satisfaction was similar with both treatments, and no serious adverse effects were recorded. CONCLUSIONS: TNS is effective in treating acute exacerbations of Psa in CF patients, but with a renal sparing potential compared with the IV preparation. PMID- 24219816 TI - Methodology for the in vitro evaluation of the delivery efficiency from valved holding chambers with facemasks. AB - BACKGROUND: In vitro performance studies of valved holding chamber (VHC)-facemask systems are a cost-effective means of circumventing potentially confounding clinical variables. This article reports results of an in vitro investigation into VHC-facemask performance, using three age-specific soft anatomical model (SAM) faces, under clinically relevant conditions. METHODS: A potentially standardized method was developed to assess VHC-facemask seal leakage, and evaluate the in vitro delivery efficiency of conventional and antistatic VHC facemask systems. A custom-built test rig and VHC cradles were used to position the VHC-facemask systems against the SAM faces, with a constant, reproducible force. A standardized simulated pediatric breathing pattern (tidal volume = 155 mL; inhalation:exhalation ratio = 40:60; 25 breaths/min) was utilized. Percent facemask seal leakage, percent delivered dose, and the effect of different numbers of simulated breaths (2 to 8) were investigated. RESULTS: Of the VHC facemask systems tested, the OptiChamber Diamond VHC with LiteTouch facemask (Diamond) system had the lowest percent seal leakage with each SAM face. Percent seal leakage from the other VHC-facemask systems was similar with SAM0 and SAM2 faces; the AeroChamber Plus Z-Stat VHC with ComfortSeal facemask (AC Z-Stat) system had a substantially greater percent seal leakage with the SAM1 face. Regardless of the number of simulated breaths, the Diamond system delivered the greatest mean percent delivered dose, with the lowest coefficient of variation, with each SAM face. Percent delivered dose did not correlate well with seal leakage, particularly for VHC-facemask systems with high seal leakage. The electrostatic properties of the VHCs appeared to influence drug delivery. CONCLUSIONS: This study describes a potentially standardized method for the evaluation of VHC-facemask systems. Use of this method enabled a comprehensive investigation into the influence of clinically relevant variables, including age specific facial anatomy, number of simulated breaths, and seal leakage, on the delivery efficiency of several commercially available VHC-facemask systems. PMID- 24219817 TI - Hand hygiene monitoring technology: protocol for a systematic review. AB - BACKGROUND: Healthcare worker hand hygiene is thought to be one of the most important strategies to prevent healthcare-associated infections, but compliance is generally poor. Hand hygiene improvement interventions must include audits of compliance (almost always with feedback), which are most often done by direct observation - a method that is expensive, subjective, and prone to bias. New technologies, including electronic and video hand hygiene monitoring systems, have the potential to provide continuous and objective monitoring of hand hygiene, regular feedback, and for some systems, real-time reminders. We propose a systematic review of the evidence supporting the effectiveness of these systems. The primary objective is to determine whether hand hygiene monitoring systems yield sustainable improvements in hand hygiene compliance when compared to usual care. METHODS/DESIGN: MEDLINE, EMBASE, CINAHL, and other relevant databases will be searched for randomized control studies and quasi-experimental studies evaluating a video or electronic hand hygiene monitoring system. A standard data collection form will be used to abstract relevant information from included studies. Bias will be assessed using the Cochrane Effective Practice and Organization of Care Group Risk of Bias Assessment Tool. Studies will be reviewed independently by two reviewers, with disputes resolved by a third reviewer. The primary outcome is directly observed hand hygiene compliance. Secondary outcomes include healthcare-associated infection incidence and improvements in hand hygiene compliance as measured by alternative metrics. Results will be qualitatively summarized with comparisons made between study quality, the measured outcome, and study-specific factors that may be expected to affect outcome (for example, study duration, frequency of feedback, use of real-time reminders). Meta-analysis will be performed if there is more than one study of similar systems with comparable outcome definitions. DISCUSSION: Electronic and video monitoring systems have the potential to improve hand hygiene compliance and prevent healthcare-associated infection, but are expensive, difficult to install and maintain, and may not be accepted by all healthcare workers. This review will assess the current evidence of effectiveness of these systems before their widespread adoption. STUDY REGISTRATION: PROSPERO registration number: CRD42013004519. PMID- 24219819 TI - Theoretical modeling of deuteration-induced shifts of the 0-0 bands in absorption spectra of selected aromatic amines: the role of the double-well potential. AB - The harmonic approximation fails for inversion of the NH2 group in the ground state of aromatic amines as this vibration is characterized by a symmetric double well potential with relatively small energy barrier. In such cases, the standard harmonic vibrational analysis is inapplicable: the inversion frequency calculated for the bottom of the potential well is strongly overestimated, while it attains imaginary values for the planar conformation of the molecule. The model calculations are discussed taking explicitly into account the presence of the double-well potential. The study is initially focused on reproduction of the deuteration-induced shifts of the 0-0 absorption band for anthranilic acid. The (incorrect) harmonic frequency of the NH2 inversion is replaced by a better one, obtained from numerical calculations employing a simple, quartic-quadratic model for the double-well potential, which is parametrized using just the harmonic frequency of the inversion and the height of the energy barrier. This operation brings theoretical results to qualitative agreement with experiment. A still better match is achieved with a modified version of the model that accounts for mixing of the NH2 inversion mode with other normal modes while retaining the initial simplicity of one-dimensional approach. The corrected results show surprisingly good accuracy, with deviations of the calculated shifts from the experimental values reduced to less than 5 cm(-1). In order to test the performance of the model for systems with higher energy barrier for the NH2 inversion, we have measured the LIF excitation spectra of three different amminobenzonitriles. Partial assignment of the 0-0 bands has been achieved based on their relative intensities for samples with different isotopic exchange ratios. Calculated shifts are in excellent agreement with experimental values for the identified bands. Theoretical predictions are used to complete the assignment of the 0-0 bands in the spectra of the studied amminobenzonitriles. PMID- 24219818 TI - Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients. AB - BACKGROUND: N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). METHODS: From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT) + CCRT to 82 patients and CCRT + adjuvant chemotherapy (AC) to 11 patients. RESULTS: The 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (p = 0.004), 49.2% and 68.5% (p = 0.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACT + CCRT and CCRT + AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (p = 0.107) when compared with RT alone group, and NACT + CCRT could significantly improve distant metastasis-free survival (p = 0.017). CONCLUSIONS: For advanced N stage NPC patients, NACT + CCRT might be a reasonable treatment strategy. PMID- 24219821 TI - Can a validated sleep apnea scoring system predict cardiopulmonary events using propofol sedation for routine EGD or colonoscopy? A prospective cohort study. AB - BACKGROUND: Obstructive sleep apnea (OSA), which is linked to the prevalence of obesity, continues to rise in the United States. There are limited data on the risk for sedation-related adverse events (SRAE) in patients with undiagnosed OSA receiving propofol for routine EGD and colonoscopy. OBJECTIVE: To identify the prevalence of OSA by using the STOP-BANG questionnaire (SB) and subsequent risk factors for airway interventions (AI) and SRAE in patients undergoing elective EGD and colonoscopy. DESIGN: Prospective cohort study. SETTING: Tertiary-care teaching hospital. PATIENTS: A total of 243 patients undergoing routine EGD or colonoscopy at Cleveland Clinic. INTERVENTION: Chin lift, mask ventilation, placement of nasopharyngeal airway, bag mask ventilation, unplanned endotracheal intubation, hypoxia, hypotension, or early procedure termination. MAIN OUTCOME MEASUREMENTS: Rates of AI and SRAE. RESULTS: Mean age of the cohort was 50 +/- 16.2 years, and 41% were male. The prevalence of SB+ was 48.1%. The rates of hypoxia (11.2% vs 16.9%; P = .20) and hypotension (10.4% vs 5.9%; P = .21) were similar between SB- and SB+ patients. An SB score >=3 was found not to be associated with occurrence of AI (relative risk [RR] 1.07, 95% confidence interval [CI] 0.79-1.5) or SRAE (RR 0.81, 95% CI, 0.53-1.2) after we adjusted for total and loading dose of propofol, body mass index (BMI), smoking, and age. Higher BMI was associated with an increased risk for AI (RR 1.02; 95% CI, 1.01 1.04) and SRAE (RR 1.03; 95% CI, 1.01-1.05). Increased patient age (RR 1.09; 95% CI, 1.02-1.2), higher loading propofol doses (RR 1.4; 95% CI, 1.1-1.8), and smoking (RR 1.9; 95% CI, 1.3-2.9) were associated with higher rates of SRAE. LIMITATIONS: Non-randomized study. CONCLUSION: A significant number of patients undergoing routine EGD and colonoscopy are at risk for OSA. SB+ patients are not at higher risk for AI or SRAE. However, other risk factors for AI and SRAE have been identified and must be taken into account to optimize patient safety. PMID- 24219820 TI - Predicting mortality in patients with in-hospital nonvariceal upper GI bleeding: a prospective, multicenter database study. AB - BACKGROUND: Nonvariceal upper GI bleeding (NVUGIB) that occurs in patients already hospitalized for another condition is associated with increased mortality, but outcome predictors have not been consistently identified. OBJECTIVE: To assess clinical outcomes of NVUGIB and identify predictors of mortality from NVUGIB in patients with in-hospital bleeding compared with outpatients. DESIGN: Secondary analysis of prospectively collected data from 2 nationwide multicenter databases. Descriptive, inferential, and multivariate logistic regression models were carried out in 338 inpatients (68.6 +/- 16.4 years of age, 68% male patients) and 1979 outpatients (67.8 +/- 17 years of age, 66% male patients). A predictive model was constructed using the risk factors identified at multivariate analysis, weighted according to the contribution of each factor. SETTINGS: A total of 23 Italian community and tertiary care centers. PATIENTS: Consecutive patients admitted for acute NVUGIB. INTERVENTIONS: Early endoscopy, medical and endoscopic treatment as appropriate. MAIN OUTCOME MEASUREMENTS: Recurrent bleeding, surgery, and 30-day mortality. RESULTS: The mortality rate in patients with in-hospital bleeding was significantly higher than that in outpatients (8.9% vs 3.8%; odds ratio [OR] 2.44; 95% confidence interval [CI], 1.57-3.79; P < .0001). Hemodynamic instability on presentation (OR 7.31; 95% CI, 2.71-19.65) and the presence of severe comorbidity (OR 6.72; 95% CI, 1.87-24.0) were the strongest predictors of death for in-hospital bleeders. Other independent predictors of mortality were a history of peptic ulcer disease and failed endoscopic treatment. Rebleeding was a strong predictor of death only for outpatients (OR 5.22; 95% CI, 2.45-11.10). Risk factors had a different prognostic impact on the 2 populations, resulting in a significantly different prognostic accuracy of the model (area under the receiver-operating characteristic curve = 0.83; 95% CI, 0.77-0-93 vs 0.74; 95% CI, 0.68-0.80; P < .02). LIMITATIONS: Study design not experimental, no data on ward specialty, potential referral bias. CONCLUSIONS: In-hospital bleeders have a significantly higher risk of death because they are sicker and more often hemodynamically unstable than outpatients. Predictors of death have a different impact in the 2 populations. PMID- 24219823 TI - Balloon dilatation for symptomatic gastric sleeve stricture. PMID- 24219822 TI - In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). AB - BACKGROUND: Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope based CLE (eCLE) for imaging Barrett's esophagus (BE). OBJECTIVE: To compare high definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. DESIGN: Multicenter, randomized, controlled trial. SETTING: Academic medical centers. PATIENTS: Adult patients with BE undergoing routine surveillance or referred for early neoplasia. INTERVENTION: Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. MAIN OUTCOME MEASUREMENTS: Diagnostic yield, performance characteristics, clinical impact. RESULTS: A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. LIMITATIONS: Tertiary-care referral centers and expert endoscopists limit generalizability. CONCLUSION: Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01124214.). PMID- 24219824 TI - Is level of neighbourhood green space associated with physical activity in green space? AB - BACKGROUND: There is accumulating evidence that greater availability of green space in a neighbourhood is associated with health benefits for the local population. One mechanism proposed for this association is that green space provides a venue for, and therefore encourages, physical activity. It has also been suggested that socio-economic health inequalities may be narrower in greener areas because of the equalised opportunity for physical activity green spaces provide. However, research exploring associations between the availability of green space and physical activity has produced mixed results. Limits to the assessment of the type and amount of physical activity which occurs specifically in green space may account for these mixed findings. This observational study was therefore concerned with the extent to which green space is a venue for physical activity and whether this could account for narrower socio-economic health inequalities in greener neighbourhoods. METHOD: Secondary analysis of cross sectional data on 3679 adults (16+) living in urban areas across Scotland matched with a neighbourhood level measure of green space availability. Associations between green space availability and both total physical activity, and activity specifically within green space, were explored using logistic regression models. Interactions between socio-economic position and physical activity were assessed. All models adjusted for age, sex and household income. RESULTS: The availability of green space in a neighbourhood was not associated with total physical activity or that specifically in green space. There was no evidence that income-related inequalities in physical activity within green space were narrower in greener areas of Scotland. CONCLUSION: Physical activity may not be the main mechanism explaining the association between green space and health in Scotland. The direct effect of perceiving a natural environment on physiological and psychological health may offer an alternative explanation. PMID- 24219826 TI - Formulation and characterization study of itraconazole-loaded microparticles. AB - The aim of the work was to realize itraconazole-loaded formulations in form of microparticles using a fast, simple and solvent free production procedure. The selected excipients were able to enhance wettability of the final product, to increase drug dissolution rate and to maintain drug in solution thanks to the formation of an emulsified system after contact with the gastrointestinal fluids. Itraconazole formulations contained a structuring lipid, a solubilizing agent and a surface active substance and were prepared by a hot melt method (MMS, melting milling-sieving). The characterization included drug content determination, granulometric distribution, differential scanning calorimetry (DSC) and in vitro drug release test, physical and technological stability after 12 months of ambient condition storage. The formulations were composed of particles with diameter lower than 355 MUm. DSC analysis evidenced that itraconazole was almost completely in the amorphous form; the results of the in vitro drug release tests showed that these formulations were able to increase the rate of the drug release compared to that of the free drug. Stability data showed no significant changes in the thermal and release profiles, confirming that the selected excipients protected the drug avoiding its conversion from amorphous state into crystalline form and maintaining unchanged the delivery behavior. PMID- 24219827 TI - Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis. AB - BACKGROUND AND AIM: The aims of this study were to investigate whether acid suppressive therapy increases the risk of spontaneous bacterial peritonitis (SBP) and to define factors associated with mortality in cirrhotic patients with SBP. METHODS: Cirrhotic patients who had undergone paracentesis after hospitalization were included. Those patients were divided into two groups according to the presence or absence of SBP. Factors associated with the development of SBP were analyzed. Mortality rates during hospitalization or within 30 days after SBP and the factors associated with mortality were also analyzed. RESULTS: A total of 1140 patients (median age, 62; men, 75%; model for end-stage liver disease [MELD] score, 17) were included. Five hundred thirty-three patients were identified as having SBP. In the logistic regression, the use of histamine-2 receptor antagonists, the use of proton pump inhibitors (PPIs), a high admission MELD score, and old age were associated with the development of SBP. The use of PPIs within 30 days (adjusted odds ratio [aOR] 1.960; 95% confidence interval [CI] 1.190-3.227; P = 0.008), a higher admission MELD score (aOR 1.054; 95% CI 1.032 1.076; P < 0.001), and hepatocellular carcinoma (aOR 1.852; 95% CI 1.256-2.730; P = 0.002) were associated with mortality after SBP. CONCLUSIONS: Acid suppressive therapy is associated with the development of SBP in cirrhotic patients with ascites. The use of PPIs is associated with mortality after SBP independent of the severity of the underlying liver disease in our retrospective cohort study. PMID- 24219825 TI - Nanoscale drug delivery platforms overcome platinum-based resistance in cancer cells due to abnormal membrane protein trafficking. AB - The development of cellular resistance to platinum-based chemotherapies is often associated with reduced intracellular platinum concentrations. In some models, this reduction is due to abnormal membrane protein trafficking, resulting in reduced uptake by transporters at the cell surface. Given the central role of platinum drugs in the clinic, it is critical to overcome cisplatin resistance by bypassing the plasma membrane barrier to significantly increase the intracellular cisplatin concentration enough to inhibit the proliferation of cisplatin resistant cells. Therefore, rational design of appropriate nanoscale drug delivery platforms (nDDPs) loaded with cisplatin or other platinum analogues as payloads is a possible strategy to solve this problem. This review will focus on the known mechanism of membrane trafficking in cisplatin-resistant cells and the development and employment of nDDPs to improve cell uptake of cisplatin. PMID- 24219828 TI - Pharmacokinetic evaluation of oral dantrolene in the dog. AB - The pharmacokinetics of dantrolene and its active metabolite, 5 hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5-hydroxydantrolene on activated whole-blood gene expression of the cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (Cmax ) was 0.43 MUg/mL, terminal half-life (t1/2 ) was 1.26 h, and area under the time concentration curve (AUC) was 3.87 MUg.h/mL. For the 10 mg/kg dose, Cmax was 0.65 MUg/mL, t1/2 was 1.21 h, and AUC was 5.94 MUg.h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t1/2 , for example, ranged from 0.43 to 6.93 h, Cmax ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole-blood expression of IL-2 and IFN gamma as measured by qRT-PCR was markedly suppressed following exposure to very high concentrations (30 and 50 MUg/mL, respectively) of both dantrolene and 5 hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing. PMID- 24219829 TI - Synthesis of the tetracyclic core of exiguaquinol. AB - A Diels-Alder reaction, a desymmetrizing aldol reaction, and a reductive Heck cyclization are employed in a short synthesis of a tetracycle relevant to exiguaquinol, a potential antibiotic. Ground-state energies of this advanced model system and the natural product rationalize the incorrect hemiaminal configuration experimentally obtained and point to the importance of the sulfonate in dictating the relative configuration of the natural product. PMID- 24219830 TI - Statin use in asthmatics on inhaled corticosteroids is associated with decreased risk of emergency department visits. AB - OBJECTIVE: Statins are hypothesized to have beneficial effects in asthma management through their pleiotropic anti-inflammatory effects. Several studies have examined this relationship, but have yielded conflicting results. This study investigates the effect of statin use on asthma-related hospitalizations and/or emergency department (ED) visits, and whether this relationship varies by concomitant inhaled corticosteroid (ICS) in a large cohort of asthma patients. METHODS: Subjects with asthma, a recent history of asthma exacerbation, and who were 18 years or older were selected from the population-based Medco Health Solutions administrative database over a 1 year period. Prescription claims for statins and asthma medications, and asthma-related hospitalizations and/or ED visits were ascertained over a 12 month follow-up period. Subjects were stratified into two groups based on their ICS use. RESULTS: A total of 3747 ICS users and 2905 non-ICS users were included in this study. Statin users represented 21% of ICS users and 11% of non-users. Among ICS users, statin use was significantly associated with decreased odds of asthma-related ED visits (OR = 0.77, 95% CI 0.64-0.94, p = 0.008), but not with asthma-related hospitalizations (OR = 1.09, 95% CI 0.92-1.30, p = 0.31). No significant associations were found among non-ICS users (for asthma-related ED visits: OR = 0.92, 95% CI 0.57-1.49, p = 0.73; asthma-related hospitalizations: OR = 1.10, 95% CI 0.85-1.41, p = 0.48). The statistical interactions between ICS and statin use on asthma-related hospitalizations and/or ED visits were not significant. CONCLUSION: Statin use is associated with fewer ED visits in asthma patients who are using ICS. PMID- 24219832 TI - Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs. AB - VSV-IFNbeta-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFNbeta-NIS administration in dogs with naturally occurring cancer. In support of this, we executed a dose-escalation study in purpose-bred dogs to determine the maximum tolerated dose (MTD) of systemic VSV-hIFNbeta-NIS, characterize the adverse event profile, and describe routes and duration of viral shedding in healthy, immune competent dogs. The data indicate that an intravenous dose of 10(10) TCID50 is well tolerated in dogs. Expected adverse events were mild to moderate fever, self limiting nausea and vomiting, lymphopenia, and oral mucosal lesions. Unexpected adverse events included prolongation of partial thromboplastin time, development of bacterial urinary tract infection, and scrotal dermatitis, and in one dog receiving 10(11) TCID50 (10 * the MTD), the development of severe hepatotoxicity and symptoms of shock leading to euthanasia. Viral shedding data indicate that detectable viral genome in blood diminishes rapidly with anti-VSV neutralizing antibodies detectable in blood as early as day 5 postintravenous virus administration. While low levels of viral genome copies were detectable in plasma, urine, and buccal swabs of dogs treated at the MTD, no infectious virus was detectable in plasma, urine, or buccal swabs at any of the doses tested. These studies confirm that VSV can be safely administered systemically in dogs, justifying the use of oncolytic VSV as a novel therapy for the treatment of canine cancer. PMID- 24219831 TI - Comparative analysis of phenolic content and profile, antioxidant capacity, and anti-inflammatory bioactivity in wild Alaskan and commercial Vaccinium berries. AB - Wild Alaskan Vaccinium berries, V. vitis-idaea (lowbush cranberry) and V. uliginosum (bog blueberry), were investigated in parallel with their commercial berry counterparts, V. macrocarpon (cranberry) and V. angustifolium (lowbush blueberry). Lowbush cranberry accumulated about twice the total phenolics (624.4 mg/100 g FW) and proanthocyanidins (278.8 mg/100 g) content as commercial cranberries, but A-type proanthocyanidins were more prevalent in the latter. Bog blueberry anthocyanin and total phenolic contents of 220 and 504.5 mg/100 g, respectively, significantly exceeded those of the lowbush blueberry. Chlorogenic acid, however, was quite high in lowbush blueberry (83.1 mg/100 g), but undetected in bog blueberry, and the proanthocyanidins of lowbush blueberry had significantly higher levels of polymerization. Antioxidant capacity (DPPH, APTS, and FRAP) correlated with phenolic content for each berry. A polyphenol-rich fraction from lowbush cranberry exhibited dose-dependent inhibition of LPS elicited induction of IL-1beta in RAW 264.7 cells, indicative of strong anti inflammatory activity. These results corroborate the historic use of wild Alaskan berries as medicinally important foods in Alaska Native communities. PMID- 24219834 TI - An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study. AB - An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization. PMID- 24219835 TI - Factors associated with the treatment of osteoporosis in Korean postmenopausal women. AB - This retrospective study was designed to investigate the treatment rate of osteopenia and osteoporosis after diagnosis and determine factors related to osteoporosis treatment in Korea. This analysis included postmenopausal women who had visited the health promotion center from March 2010 to May 2011 (n = 375) and been diagnosed with osteoporosis (19.5%) or osteopenia (45.9%). Telephone surveys were performed one year after diagnosis. We employed multiple logistic regression to determine factors associated with treatment using clinical risk factors as covariates in a FRAX model. Receipt of osteoporosis treatment (nutrition, exercise, and medications) to prevent osteoporotic fracture was reported by 108 of 172 (63.4%) women with osteopenia and 66 of 73 (90.4%) with osteoporosis. Only consultation with a doctor for osteopenia or osteoporosis was significantly related to receiving osteoporosis treatment for osteopenia (odds ratio [OR], 5.01; 95% confidence interval [CI], 2.01-12.00) and osteoporosis (OR, 4.91; 95% CI, 1.16-20.75). In the osteopenic group, increased age, being a current smoker, having a history of parental fracture or previous fracture, and secondary osteoporosis were related to consultation with a doctor. Of women with osteopenia 36.6% and 64.4% with osteoporosis received consultation with a doctor. Consultation with a doctor for osteopenia or osteoporosis after being diagnosed could be an effective strategy to increase osteoporosis treatment. PMID- 24219836 TI - Periostin expression is upregulated and associated with myocardial fibrosis in human failing hearts. AB - BACKGROUND AND PURPOSE: Periostin, a matricellular protein, plays an important role in cardiac development and remodeling. Its expression profile and the association with myocardial fibrosis have not been investigated in human failing hearts. This work aimed to explore the behavior and pathologic significance of periostin in signifying collagen fibrogenesis in human hearts from patients with end-stage heart failure. METHODS AND SUBJECTS: Tissues were collected from heart transplant recipients and the control hearts were from unmatched donors. Periostin mRNA and protein were detected using quantitative real-time polymerase chain reaction and Western blotting. Immunohistochemistry staining was employed to directly detect the protein level and distribution of periostin in heart tissues. The extent of myocardial fibrosis was expressed by the percentage of Masson's trichrome staining. Gelatin zymography was used to detect the activities of matrix metalloproteinase (MMP)2 and MMP9. RESULTS: A low level of periostin mRNA expression was found in control hearts while not detectable at the protein level. Periostin mRNA was increased significantly in failing myocardium compared to that of controls. Periostin was distributed extensively in left ventricle and interventricular septum of the failing hearts. Correlation analysis showed periostin protein expression was positively associated with myocardial fibrosis as well as left ventricular diastolic dimension. The distribution and extent of periostin was consistent with that of myocardial fibrosis. MMP2 activity has an obvious increase about fourfold in heart tissues from HF patients. But there is no quantitative association with the expression of periostin. CONCLUSIONS: Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients. PMID- 24219837 TI - Clonal diversity and estimation of relative clone age: application to agrobiodiversity of yam (Dioscorea rotundata). AB - BACKGROUND: Clonal propagation is a particular reproductive system found in both the plant and animal kingdoms, from human parasites to clonally propagated crops. Clonal diversity provides information about plant and animal evolutionary history, i.e. how clones spread, or the age of a particular clone. In plants, this could provide valuable information about agrobiodiversity dynamics and more broadly about the evolutionary history of a particular crop. We studied the evolutionary history of yam, Dioscorea rotundata. In Africa, Yam is cultivated by tuber clonal propagation. RESULTS: We used 12 microsatellite markers to identify intra-clonal diversity in yam varieties. We then used this diversity to assess the relative ages of clones. Using simulations, we assessed how Approximate Bayesian Computation could use clonal diversity to estimate the age of a clone depending on the size of the sample, the number of independent samples and the number of markers. We then applied this approach to our particular dataset and showed that the relative ages of varieties could be estimated, and that each variety could be ranked by age. CONCLUSIONS: We give a first estimation of clone age in an approximate Bayesian framework. However the precise estimation of clone age depends on the precision of the mutation rate. We provide useful information on agrobiodiversity dynamics and suggest recurrent creation of varietal diversity in a clonally propagated crop. PMID- 24219838 TI - pGALS - paediatric Gait Arms Legs and Spine: a simple examination of the musculoskeletal system. AB - We describe pGALS (paediatric Gait, Arms, Legs and Spine) - a simple quick musculoskeletal assessment to distinguish abnormal from normal joints in children and young people. The use of pGALS is aimed at the non-specialist in paediatric musculoskeletal medicine as a basic clinical skill to be used in conjunction with essential knowledge about red flags, normal development and awareness of patterns of musculoskeletal pathologies. pGALS has been validated in school-aged children and also in the context of acute general paediatrics to detect abnormal joints. We propose that pGALS is an important part of basic clinical skills to be acquired by all doctors who may be involved in the care of children. The learning of pGALS along with basic knowledge is a useful way to increase awareness of joint disease, facilitate early recognition of joint problems and prompt referral to specialist teams to optimise clinical outcomes. We have compiled this article as a resource that can be used by the paediatric rheumatology community to facilitate teaching. PMID- 24219839 TI - Homo-Roche ester derivatives by asymmetric hydrogenation and organocatalysis. AB - Asymmetric hydrogenation routes to homologues of The Roche ester tend to be restricted to hydrogenations of itaconic acid derivatives, that is, substrates that contain a relatively unhindered, 1,1-disubstituted alkene. This is because in hydrogenations mediated by RhP2 complexes, the typical catalysts, it is difficult to obtain high conversions using the alternative substrate for the same product, the isomeric trisubstituted alkenes (D in the text). However, chemoselective modification of the identical functional groups in itaconic acid derivatives are difficult; hence, it would be favorable to use the trisubstituted alkene. Trisubstituted alkene substrates can be hydrogenated with high conversions using chiral analogs of Crabtree's catalyst of the type IrN(carbene). This paper demonstrates that such reactions are scalable (tens of grams) and can be manipulated to give optically pure homo-Roche ester chirons. Organocatalytic fluorination, chlorination, and amination of the homo-Roche building blocks was performed to demonstrate that they could easily be transformed into functionalized materials with two chiral centers and alpha,omega-groups that provide extensive scope for modifications. A synthesis of (S,S)- and (R,S)-gamma hydroxyvaline was performed to illustrate one application of the amination product. PMID- 24219840 TI - Knowledge, attitudes and competence in nursing practice of typhoon disaster relief work among Chinese nurses: a questionnaire survey. AB - The aim of this paper is to examine the relationships among nurses' knowledge of, attitudes towards and level of competence in nursing practice, as well as factors influencing nurses' competence in nursing practice, in typhoon disaster relief work. A cross-sectional descriptive study was conducted using a self-developed questionnaire to obtain data from 607 nurses working in four tertiary hospitals and two secondary hospitals in Fujian, China, in November 2011. Our findings show that the nurses' average percentage scores on their responses to questions in the domains of knowledge, attitudes and practice were 66.33%, 68.87% and 67.60%, respectively. The findings demonstrated a significant positive relationship between nurses' attitudes and their practice. Nurses' working unit, prior training in typhoon disaster relief, current position of employment and attitudes were significant predictors of nurses' competence in practice. The results indicate that strategies need to be developed for nurses to improve their knowledge, attitudes and practice. PMID- 24219841 TI - Specific immunotherapy in asthma: a comprehensive review. AB - BACKGROUND: The prescription of allergen immunotherapy (SIT) in asthma remains a matter of debate and official guidelines often do not provide clear recommendations in this regard. METHODS: An extensive review of the literature was untaken. RESULTS: There are many robust studies with SCIT and SLIT showing positive results related to improving asthma symptoms, in particular when asthma was associated with rhinitis. In addition, there are several favourable meta analyses, although their validity is limited by the heterogeneity of the trials included. The disease modifying effect of SIT (prevention of asthma onset and long-lasting effects) should be considered when prescribing this treatment. Regarding safety, fatalities seem to be rare: in Europe no fatality has been reported over the last two decades, and the same has been observed in USA in the last 4 years. Uncontrolled asthma is universally recognized as the most important risk factor for severe adverse events, but there is no clear demonstration that SIT can worsen or induce asthma. In contrast, of the few studies specifically designed to evaluate asthma, none had a formal sample size calculation, and pulmonary function was assessed as primary outcome only sporadically. CONCLUSIONS: According to the presently available evidence, SLIT and SCIT can be used in asthma associated with rhinitis (the most common condition), provided that asthma is adequately controlled by pharmacotherapy. In such cases, a measurable clinical benefit on asthma symptoms can be expected. SIT cannot be presently recommended as single therapy when asthma is the unique manifestation of respiratory allergy. PMID- 24219842 TI - The Pediatric Asthma Control and Communication Instrument for the Emergency Department (PACCI-ED) improves physician assessment of asthma morbidity in pediatric emergency department patients. AB - OBJECTIVES: To determine whether the Pediatric Asthma Control and Communication Instrument for the Emergency Department (PACCI-ED), a 12-item questionnaire, can help ED attendings accurately assess a patient's asthma control and morbidity. METHODS: This was a randomized-controlled trial performed at an urban pediatric ED of children aged 1-17 years presenting with an asthma exacerbation. Parents answered PACCI-ED questions about their children's asthma. Attendings were randomized to view responses to the PACCI-ED (intervention group) or to be blinded to the completed PACCI-ED (control group). The two groups were compared on their empirical clinical assessment of: (1) chronic asthma control categories, (2) asthma trajectory (stable, worsening or improving), (3) patient adherence to controller medications, and (4) burden of disease for the patient's family. The validated PACCI algorithm was used as the criterion standard for these four outcomes. Accuracy of clinical assessment was compared between intervention and control groups using chi-squared tests and an intention-to-treat approach. RESULTS: Seventeen ED attendings were enrolled in the study and 77 children visits were included in the analysis. There were no significant differences between the intervention and the control groups for child's gender, age, race, and asthma characteristics. Intervention group attendings were more accurate than control group attendings in assessing the category of chronic asthma control (43% versus 19%; p = 0.03), disease trajectory (72% versus 45%; p = 0.02), and the disease burden for families (74% versus 35%; p = 0.001) over the past 12 months. There was a trend towards more accuracy of intervention versus control attendings for estimating patient adherence to controller medications (72% versus 48%; p = 0.06). CONCLUSIONS: The PACCI-ED improves the assessment of asthma control, trajectory, and burden by ED attendings, and may help assessment of asthma medication adherence and prior asthma exacerbations. The PACCI-ED can be used to improve provider assessment of asthma morbidity during pediatric ED visits for asthma exacerbations, and to identify children who may benefit from interventions to reduce asthma morbidity. PMID- 24219843 TI - Defining traumatic brain injury in children and youth using international classification of diseases version 10 codes: a systematic review protocol. AB - BACKGROUND: Although healthcare administrative data are commonly used for traumatic brain injury research, there is currently no consensus or consistency on using the International Classification of Diseases version 10 codes to define traumatic brain injury among children and youth. This protocol is for a systematic review of the literature to explore the range of International Classification of Diseases version 10 codes that are used to define traumatic brain injury in this population. METHODS/DESIGN: The databases MEDLINE, MEDLINE In-Process, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Database of Systematic Reviews will be systematically searched. Grey literature will be searched using Grey Matters and Google. Reference lists of included articles will also be searched. Articles will be screened using predefined inclusion and exclusion criteria and all full-text articles that meet the predefined inclusion criteria will be included for analysis. The study selection process and reasons for exclusion at the full-text level will be presented using a PRISMA study flow diagram. Information on the data source of included studies, year and location of study, age of study population, range of incidence, and study purpose will be abstracted into a separate table and synthesized for analysis. All International Classification of Diseases version 10 codes will be listed in tables and the codes that are used to define concussion, acquired traumatic brain injury, head injury, or head trauma will be identified. DISCUSSION: The identification of the optimal International Classification of Diseases version 10 codes to define this population in administrative data is crucial, as it has implications for policy, resource allocation, planning of healthcare services, and prevention strategies. It also allows for comparisons across countries and studies. This protocol is for a review that identifies the range and most common diagnoses used to conduct surveillance for traumatic brain injury in children and youth. This is an important first step in reaching an appropriate definition using International Classification of Diseases version 10 codes and can inform future work on reaching consensus on the codes to define traumatic brain injury for this vulnerable population. PMID- 24219844 TI - A new type of aortic valved stent with good stability and no influence on coronary artery. AB - BACKGROUND: To evaluated the feasibility and safety of new aortic valved stents in transcatheter aortic valve implantation (TAVI) using retrograde approach by in vitro testing and animal implantation. MATERIALS AND METHODS: The fluid passing test, expanding and releasing tests, static and releasing tests in tube were performed for new valved stents. Transvalvular pressure gradient, effective orifice area, pre-implantation and post-implantation regurgitant volume for the new stents were detected. Then, the new stents were implanted in six pigs using retrograde approach. These pigs were euthanized 12 h after the implantation for anatomic evaluation. RESULTS: In vitro tests showed that the closure of the new stents leaflets were effective, and stents could be released through catheter, then expanded completely and fixed fast in the tube. The coronary artery flow rates did not changed significantly after implantation (P > 0.05), while aortic regurgitant volumes were obviously reduced (P < 0.05). No significant difference in the transvalvular pressure gradient and effective orifice area of the new stents implanted within or above the valve leaflets was found (P > 0.05). In vivo experiments indicated that TAVI was successfully performed in six pigs using retrograde approach. However, one pig was died 10 h after the implantation since the stent was not expanded completely. The leaflets in stents were opening well and no valvular regurgitation was observed in the other five pigs. And thrombosis was not found. DISCUSSION AND CONCLUSION: The new type of aortic valved stent designed in this study was characterized with good stability and could avoid the impact caused by valve leaflets on the coronary artery. PMID- 24219845 TI - Combining ECMO with IABP for the treatment of critically Ill adult heart failure patients. AB - OBJECTIVE: To discuss the experience of combining extra-corporeal membrane oxygenation (ECMO) with intra-aortic balloon pump (IABP) for the treatment of acute heart failure in critically ill adults. METHODS: The clinical data of 54 patients who received ECMO combined with IABP due to acute heart failure between January 2008 and July 2012 were retrospectively analysed. Thirty-eight of the patients were male, and 16 were female; the mean age was 57+/-11. Thirty-nine of the patients received IABP first but were still unable to maintain adequate circulation, and were then given ECMO; the other 15 underwent ECMO first, but due to increased left ventricular load, the opening of the aortic valve was restricted and IABP was then introduced. RESULTS: Thirty-four patients (63%) were successfully weaned from ECMO; 21 patients (38.9%) survived to discharge. Major complications that occurred were renal failure (27 cases), infection (20 cases), blood plasma leakage in the oxygenator (13 cases), bleeding (18 cases), limb ischaemia (eight cases), and neurological complications (seven cases); in the group of patients who did not survive, the rates of bleeding occurrence, infection and renal failure were markedly higher than in the survived patients group. In both groups, the longer the patients were on support, the more improvement they showed in terms of MAP, CVP, Lac, SvO2 and IS. CONCLUSION: ECMO and IABP may have synergistic effects and play complementary roles in the treatment of acute cardiac failure; with timely administration, active prevention and treatment of complications, they can improve treatment outcome. PMID- 24219846 TI - Information needs of family carers of people with diabetes at the end of life: a literature review. AB - BACKGROUND: Recent research identified the issue that family carers of people with diabetes at the end of life (EOL) did not receive sufficient information to enable them to help their relative manage their diabetes at the EOL. AIM: The aim of the current study was to undertake a literature review to identify the information needs of family carers of people with diabetes at the EOL. METHOD: A comprehensive review of the literature was conducted by searching the following databases: CINAHL, PubMed, PsychInfo, Scopus, and SocINDEX. The grey literature was also searched for papers relevant to the aim. All study designs were included. A content analysis of relevant papers was undertaken to identify themes. RESULTS: Sixteen of the more than 300 papers identified addressed the information needs of family carers of people with diabetes at the EOL and were included in the review. Five key themes were identified from the papers reviewed: (1) performing diabetes care tasks, (2) focus of care, (3) blood glucose management, (4) EOL stages, and (5) involving patients and family carers in decisions about diabetes care. Most of the 16 papers represented the views of health professionals and focused on the need to provide information about the medical aspects of diabetes management. CONCLUSIONS: The review suggests further research is needed to identify the information needs of family carers of people with diabetes at the EOL to enable interventions to be developed to support the family carers and meet their unique information needs. PMID- 24219847 TI - A quantitative evolutionary theory of adaptive behavior dynamics. AB - The idea that behavior is selected by its consequences in a process analogous to organic evolution has been discussed for over 100 years. A recently proposed theory instantiates this idea by means of a genetic algorithm that operates on a population of potential behaviors. Behaviors in the population are represented by numbers in decimal integer (phenotypic) and binary bit string (genotypic) forms. One behavior from the population is emitted at random each time tick, after which a new population of potential behaviors is constructed by recombining parent behavior bit strings. If the emitted behavior produced a benefit to the organism, then parents are chosen on the basis of their phenotypic similarity to the emitted behavior; otherwise, they are chosen at random. After parent behavior recombination, the population is subjected to a small amount of mutation by flipping random bits in the population's bit strings. The behavior generated by this process of selection, reproduction, and mutation reaches equilibrium states that conform to every empirically valid equation of matching theory, exactly and without systematic error. These equations are known to describe the behavior of many vertebrate species, including humans, in a variety of experimental, naturalistic, natural, and social environments. The evolutionary theory also generates instantaneous dynamics and patterns of preference change in constantly changing environments that are consistent with the dynamics of live-organism behavior. These findings support the assertion that the world of behavior we observe and measure is generated by evolutionary dynamics. PMID- 24219848 TI - A role for the developing lexicon in phonetic category acquisition. AB - Infants segment words from fluent speech during the same period when they are learning phonetic categories, yet accounts of phonetic category acquisition typically ignore information about the words in which sounds appear. We use a Bayesian model to illustrate how feedback from segmented words might constrain phonetic category learning by providing information about which sounds occur together in words. Simulations demonstrate that word-level information can successfully disambiguate overlapping English vowel categories. Learning patterns in the model are shown to parallel human behavior from artificial language learning tasks. These findings point to a central role for the developing lexicon in phonetic category acquisition and provide a framework for incorporating top down constraints into models of category learning. PMID- 24219850 TI - A nonparametric Bayesian framework for constructing flexible feature representations. AB - Representations are a key explanatory device used by cognitive psychologists to account for human behavior. Understanding the effects of context and experience on the representations people use is essential, because if two people encode the same stimulus using different representations, their response to that stimulus may be different. We present a computational framework that can be used to define models that flexibly construct feature representations (where by a feature we mean a part of the image of an object) for a set of observed objects, based on nonparametric Bayesian statistics. Austerweil and Griffiths (2011) presented an initial model constructed in this framework that captures how the distribution of parts affects the features people use to represent a set of objects. We build on this work in three ways. First, although people use features that can be transformed on each observation (e.g., translate on the retinal image), many existing feature learning models can only recognize features that are not transformed (occur identically each time). Consequently, we extend the initial model to infer features that are invariant over a set of transformations, and learn different structures of dependence between feature transformations. Second, we compare two possible methods for capturing the manner that categorization affects feature representations. Finally, we present a model that learns features incrementally, capturing an effect of the order of object presentation on the features people learn. We conclude by considering the implications and limitations of our empirical and theoretical results. PMID- 24219849 TI - Sensory optimization by stochastic tuning. AB - Individually, visual neurons are each selective for several aspects of stimulation, such as stimulus location, frequency content, and speed. Collectively, the neurons implement the visual system's preferential sensitivity to some stimuli over others, manifested in behavioral sensitivity functions. We ask how the individual neurons are coordinated to optimize visual sensitivity. We model synaptic plasticity in a generic neural circuit and find that stochastic changes in strengths of synaptic connections entail fluctuations in parameters of neural receptive fields. The fluctuations correlate with uncertainty of sensory measurement in individual neurons: The higher the uncertainty the larger the amplitude of fluctuation. We show that this simple relationship is sufficient for the stochastic fluctuations to steer sensitivities of neurons toward a characteristic distribution, from which follows a sensitivity function observed in human psychophysics and which is predicted by a theory of optimal allocation of receptive fields. The optimal allocation arises in our simulations without supervision or feedback about system performance and independently of coupling between neurons, making the system highly adaptive and sensitive to prevailing stimulation. PMID- 24219851 TI - Putting retrieval-induced forgetting in context: an inhibition-free, context based account. AB - We present a new theoretical account of retrieval-induced forgetting (RIF) together with new experimental evidence that fits this account and challenges the dominant inhibition account. RIF occurs when the retrieval of some material from memory produces later forgetting of related material. The inhibition account asserts that RIF is the result of an inhibition mechanism that acts during retrieval to suppress the representations of interfering competitors. This inhibition is enduring, such that the suppressed material is difficult to access on a later test and is, therefore, recalled more poorly than baseline material. Although the inhibition account is widely accepted, a growing body of research challenges its fundamental assumptions. Our alternative account of RIF instead emphasizes the role of context in remembering. According to this context account, both of 2 tenets must be met for RIF to occur: (a) A context change must occur between study and subsequent retrieval practice, and (b) the retrieval practice context must be the active context during the final test when testing practiced categories. The results of 3 experiments, which directly test the divergent predictions of the 2 accounts, support the context account but cannot be explained by the inhibition account. In an extensive discussion, we survey the literature on RIF and apply our context account to the key findings, demonstrating the explanatory power of context. PMID- 24219852 TI - Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial. AB - BACKGROUND AND AIM: Despite the benefits of endoscopic nasobiliary drainage (NBD) in endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) and nose/throat discomfort can result. We aimed to determine whether the use of a smaller catheter alleviates these complications. METHOD: A randomized, controlled trial at a tertiary care center compared 4 Fr and 6 Fr NBD catheters; 165 ERCP patients with naive papillae were randomly assigned to a catheter-size group. RESULTS: The prevalence of PEP was significantly lower in the 4 Fr group (3.7%; 3/82) than in the 6 Fr group (15.7%; 13/83; P = 0.019). No spontaneous catheter displacement occurred within 24 h. Discomfort visual analog scores were 2.6 and 4.3 in the 4 Fr and 6 Fr groups, respectively (P = 0.0048) on procedure day; on the following day, the scores were 2.3 and 3.6 (P = 0.028). Bile output was 16.3 mL/h and 21.4 mL/h in the 4 Fr and 6 Fr groups (P = 0.051). On obstructive jaundice subgroup analysis, bile drainage was 19.2 mL/h and 22.1 mL/h in the 4 Fr and 6 Fr groups (P = 0.40). The 4 Fr group required 5.6 days to reduce bilirubin levels versus 6.1 days in the 6 Fr group (P = 0.51). CONCLUSIONS: In patients with naive papillae, lower rates of PEP and less nose/throat discomfort are associated with the use of 4 Fr NBD catheters. In patients with obstructive jaundice, 4 Fr and 6 Fr catheters are comparable with regard to bile output and bilirubin level reduction. PMID- 24219853 TI - Chiral phosphoric acid catalyzed enantioselective desymmetrization of meso epoxides by thiols. AB - The first chiral Bronsted acid catalyzed asymmetric nucleophilic ring-opening reaction of meso-epoxides is described. In the presence of TRIP, a range of meso epoxides could undergo smooth ring-opening reactions by aryl thiols with good efficiency and enantioselectivity. PMID- 24219854 TI - Fourier self-deconvolution of the IR spectra as a tool for investigation of distinct functional groups in porous materials: Bronsted acid sites in zeolites. AB - For many decades, IR and FT-IR spectroscopy has generated valuable information about different functional groups in zeolites, metal-organic frameworks (MOFs), and other porous materials. However, this technique cannot distinguish between functional groups in different local environments. Our study demonstrates that this limitation could be overcome by using Fourier self-deconvolution of infrared spectra (FSD-IR). We apply this method to study three acidic mordenite zeolites and show (i) that these zeolites contain six distinct Bronsted acid sites (BAS) as opposed to 2-4 different BAS previously considered in literature and (ii) that the relative amounts of these BAS are different in the three zeolites examined. We then analyze possible locations of six BAS in the mordenite structure and explain a number of conflicting results in literature. On this basis, we conclude that the FSD-IR method allows direct visualization and examination of distributions of distinct BAS in zeolites, thus providing a unique research opportunity, which no other method can provide. Given the similarities in the IR analysis of different functional groups in solids, we expect that the FSD-IR method will be also instrumental in the research into other porous materials, such as solid oxides and MOFs. The latter point is illustrated by FSD of the IR spectrum of hydroxyl groups in a sample of alpha-alumina. PMID- 24219855 TI - Novel self-assembly graft copolymers as carriers for anti-inflammatory drug delivery. AB - Indomethacin (IMC) and quercetin (QUE) as typical models of anti-inflammatory drugs were loaded into the micelles of new amphiphilic graft copolymers, comprising caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) units in the main chain and poly(meth)acrylic acid side chains (PAA/PMAA), which were studied as the carriers of drugs. The macromolecules were self-assembled by solvent evaporation or dialysis. The critical micelle concentration (CMC) ranged from 0.015 to 0.199 mg/ml. The copolymer composition, grafting degree and length of side chains, nature and content of hydrophobic/hydrophilic part, were investigated as the main parameters responsible for the properties of nanoparticles including their stability, core-drug interactions, improved drug solubility, and in consequence the efficiency of drug-loading and drug release profiles. The hydrodynamic diameters of particles measured by dynamic light scattering (DLS) ranged from 50 to 275 nm, and increased after loading with drug. In vitro release experiments performed at various pH (5.0 and 7.4) indicated faster release behavior from nanoparticles in acidic conditions (55-95% vs. 25 45% within 75 h). PMID- 24219856 TI - Targeted local simultaneous iontophoresis of chemotherapeutics for topical therapy of head and neck cancers. AB - The objective was to investigate the feasibility of using buccal iontophoresis for the simultaneous delivery of chemotherapeutic agents with a view to developing a new approach to treat head and neck cancers. Short duration cathodal iontophoresis of 5-fluorouracil (5-FU; 20mM) and leucovorin (LV; 10 mM) at 1 mA/cm(2) for 10 or 20 min from aqueous solution and a 2% hydroxyethyl cellulose gel at pH 7.6 was evaluated using bovine mucosa in vitro. Iontophoresis resulted in a statistically significant increase in the mucosal deposition of both drugs as compared to passive diffusion (Student's t-test, alpha=0.05); in each case, drug delivery was selective for deposition with no permeation being observed. After 20 min of iontophoresis, there was an ~ 8-fold enhancement for 5-FU (1.46 +/- 0.86 and 11.93 +/- 3.81 MUg/cm(2), respectively) and a 3-fold increase for LV (8.31 +/- 2.44 and 25.08 +/- 6.89 MUg/cm(2), respectively) when using aqueous solutions. The same trend was observed when the gel was applied for 10 min; passive delivery of 5-FU from the gel resulted in non-detectable levels in the mucosa, while 4.62 +/- 1.76 MUg/cm(2) were deposited in the mucosa following iontophoresis. Similarly, iontophoretic delivery of LV from the gel resulted in ~ 3-fold higher deposition as compared to passive diffusion (6.71 +/- 1.36 and 21.12 +/- 9.94 MUg/cm(2), respectively). No drug permeation was observed in either case. In conclusion, iontophoresis can be used for targeted topical delivery of chemotherapeutics to the buccal mucosa and may enable less invasive local therapy of head and neck cancers. PMID- 24219857 TI - Absorption and elimination of imatinib through the rat intestine in vitro. AB - Imatinib is a potent selective inhibitor of tyrosine kinases and is used primarily in the treatment of chronic myeloid leukemia and the gastrointestinal stromal tumour. Although, it is well established that imatinib is a substrate of several transport proteins which are also active in the intestinal mucosa, the mechanisms of imatinib intestinal absorption and elimination were not systematically investigated yet. To do that, we used a Sweetana-Grass type of diffusion chambers with segments of rat intestine as a model of the intestinal mucosa, measured the permeability coefficients of imatinib and its major metabolite (N-desmethyl imatinib) in both directions with and without specific and general inhibition of active transport, and calculated the efflux ratios. The results show that the good bioavailability of imatinib is highly likely achieved by its active absorption from the intestine and that its active elimination through the intestinal mucosa is mediated by a synergistic activity of organic cation transporter 1 in the basolateral membrane and the added activity of two efflux proteins (P-glycoprotein and breast cancer resistant protein) in the apical membrane of enterocytes of the rat ileum. Interestingly, it was found that N-desmethyl imatinib is only transported by P-glycoprotein. PMID- 24219859 TI - Changes in choroidal thickness after photodynamic therapy in patients with central serous chorioretinopathy. PMID- 24219858 TI - Activation of lateral hypothalamic mGlu1 and mGlu5 receptors elicits feeding in rats. AB - Metabotropic glutamate receptors (mGluRs) have been popular drug targets for a variety of central nervous system (CNS) disease models, ranging from seizures to schizophrenia. The current study aimed to determine whether mGluRs participate in lateral hypothalamic (LH) stimulation of feeding. To this end, we used satiated adult male Sprague-Dawley rats stereotaxically implanted with indwelling bilateral LH guide cannulas to determine if injection of (1S,3R)-1 aminocyclopentane-1,3-dicarboxylic acid (ACPD), a broad mGluR group I and II agonist, would elicit feeding. Administration of 100 nmol ACPD induced feeding with a short latency. Similarly, unilateral LH injection of the selective mGluR group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) elicited significant feeding beginning 60 min postinjection and continuing until 4 h postinjection. Administration of the mGluR5 agonist, (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) produced a smaller delayed feeding response. These delayed but prolonged eating responses suggest that activation of LH mGluR1 and/or mGluR5 might be sufficient to elicit feeding. To determine which subtypes were involved, LH DHPG injections were preceded by LH injection of either the group I antagonist n-phenyl-7 (hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), the mGluR1 antagonist 6-amino-n-cyclohexyl-n,3-dimethylthiazolo[3,2-a]benzimi dazole-2-carboxamide hydrochloride (YM-298198) or the mGluR5 antagonist 3-((2-methyl-4 thiazolyl)ethynyl)pyridine (MTEP), and food intake was measured. PHCCC blocked DHPG-elicited feeding, and each of the other antagonists produced significant feeding suppression. These findings suggest roles for mGluR1 and/or mGluR5 in lateral hypothalamic circuits capable of stimulating feeding behavior. PMID- 24219860 TI - The effects of rituximab on serum IgE and BAFF. AB - BACKGROUND: There are few treatment options for patients with severe atopic asthma. Antagonism of IgE is an effective strategy. We investigated, by utilizing serum samples from a clinical trial of Rituximab in patients with Idiopathic Thrombocytopenic Purpura, if B cell depletion would decrease serum IgE and therefore be a potential therapeutic option. FINDINGS: In a placebo-controlled randomized clinical trial of Rituximab, an anti-CD20 molecule, there were no significant differences in serum levels of IgE or BAFF levels between the two treatment groups at 3 or 6 months irrespective of the baseline serum IgE levels. CONCLUSIONS: Since Rituximab did not significantly decrease serum IgE levels, this proof of concept study suggests that Rituximab may not be a useful treatment strategy for patients with severe IgE mediated disease. PMID- 24219861 TI - Quantitative wear and wear damage analysis of composite resins in vitro. AB - The aim of this study was to investigate volume loss and worn surfaces' morphologies of eight composite resins: Durafill VS (DUR), Clearfil AP-X (APX), Filtek Z250 (Z250), Filtek Supreme XT (FIL), Kalore (KAL), MI Flow (MFL), Venus Diamond (VED) and Venus Pearl (VEP). Disc-shaped specimens were fabricated and mounted in a ball-on-disc wear testing machine and abraded in water or with the third-body media, poppy seed slurry and polymethyl methacrylate (PMMA) slurry. Volume loss (n=5) was determined after 50k sliding cycles, and analyzed using two way ANOVA (alpha=0.05). The worn surfaces were examined with SEM. Two-way ANOVA suggested significant interaction between composite and wear condition. DUR, KAL and MFL showed low wear in water. DUR, Z250 and FIL showed moderate wear with PMMA slurry, whereas APX, KAL and MFL were deeper abraded. Under the action of poppy seed slurry DUR proved high volume loss. SEM showed that Z250, FIL and MFL were uniformly abraded in water. KAL and MFL with poppy seed were heavily destructed, whereas VED and VEP appeared very smooth. KAL and MFL abraded with PMMA slurry showed many cracks, but VEP remained crack-free and smooth. Volume loss and worn surfaces' morphologies varied with type of composite and third-body media used. PMID- 24219862 TI - Modification and unexpected reactivity of 2-borylbenzaldimines: acylated and silylated derivatives as well as dimeric compounds. AB - Various novel N-alkyl and N-benzyl 2-borylbenzaldimines 3 were prepared by condensation of 2-(dimesitylboryl)benzaldehyde (1) with amines. Further functionalization of compound 3e was possible by deprotonation and subsequent regioselective reaction with electrophiles to give compounds 4. Applying similar conditions to 3a led to the unexpected formation of hitherto unknown dimeric compounds (5 and 6). All structural types were fully characterized, including by X-ray diffraction (XRD). Furthermore, quantum chemical calculations on the SCS MP2 and DFT levels gave insights into the reaction mechanisms and the stereoselectivity. The B/N bonding situation in these molecules was analyzed using Wiberg bond indices. Preliminary UV-vis and fluorescence measurements indicate that the substitution reaction leading to compounds 4 can be utilized to tune the photophysical properties of these compounds. PMID- 24219863 TI - A hierarchical frailty model for familial testicular germ-cell tumors. AB - Using a 2-level hierarchical frailty model, we analyzed population-wide data on testicular germ-cell tumor (TGCT) status in 1,135,320 two-generational Norwegian families to examine the risk of TGCT in family members of patients. Follow-up extended from 1954 (cases) or 1960 (unaffected persons) to 2008. The first-level frailty variable was compound Poisson-distributed. The underlying Poisson parameter was randomized to model the frailty variation between families and was decomposed additively to characterize the correlation structure within a family. The frailty relative risk (FRR) for a son, given a diseased father, was 4.03 (95% confidence interval (CI): 3.12, 5.19), with a borderline significantly higher FRR for nonseminoma than for seminoma (P = 0.06). Given 1 affected brother, the lifetime FRR was 5.88 (95% CI: 4.70, 7.36), with no difference between subtypes. Given 2 affected brothers, the FRR was 21.71 (95% CI: 8.93, 52.76). These estimates decreased with the number of additional healthy brothers. The estimated FRRs support previous findings. However, the present hierarchical frailty approach allows for a very precise definition of familial risk. These FRRs, estimated according to numbers of affected/nonaffected family members, provide new insight into familial TGCT. Furthermore, new light is shed on the different familial risks of seminoma and nonseminoma. PMID- 24219864 TI - A study on the effect of different rifle calibres in euthanisation of grey seals (Halichoerus grypus) in seal traps in the Baltic Sea. AB - BACKGROUND: In recent years, the euthanasia of seals has been discussed internationally and concern has been raised regarding the use of rifles, the effect of different calibres, and which calibres are sufficient for humane euthanasia. This study therefore investigated the effect of different firearm calibres on euthanasia of grey seals (Halichoerus grypus) in traps, and provides information for the development and refinement of regulations for hunting seals in the wild. FINDINGS: The effect of different calibres was studied in 19 seals shot in the head and neck at close range. All seals were necropsied and radiographed to characterize the injuries caused by the bullets. All tested calibres, 5.6 mm bullet diameter or larger, and .12 shotgun, were sufficiently effective to cause severe skull fractures, meningeal haemorrhages and instant death. CONCLUSIONS: Rifles with 5.6 mm bullet diameter or larger, and a .12 shotgun loaded with a slug fired at close range to the head and neck of grey seals all caused instant death and can therefore be recommended for hunting seals in the wild. PMID- 24219865 TI - siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa. AB - To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P<0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections. PMID- 24219866 TI - Demethylation of CpG islands in the 5' upstream regions mediates the expression of the human testis-specific gene MAGEB16 and its mouse homolog Mageb16. AB - Tissue-specific gene expression is regulated by epigenetic modification involving trans-acting factors. Here, we identified that the human MAGEB16 gene and its mouse homolog, Mageb16, are only expressed in the testis. To investigate the mechanism governing their expression, the promoter methylation status of these genes was examined in different samples. Two CpG islands (CGIs) in the 5' upstream region of MAGEB16 were highly demethylated in human testes, whereas they were methylated in cells without MAGEB16 expression. Similarly, the CGI in Mageb16 was hypomethylated in mouse testes but hypermethylated in other tissues and cells without Mageb16 expression. Additionally, the expression of these genes could be activated by treatment with the demethylation agent 5'-aza-2' deoxycytidine (5'-aza-CdR). Luciferase assays revealed that both gene promoter activities were inhibited by methylation of the CGI regions. Therefore, we propose that the testis-specific expression of MAGEB16 and Mageb16 is regulated by the methylation status of their promoter regions. PMID- 24219867 TI - Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway. AB - Orostachys japonicus shows various biological activities. However, the molecular mechanisms remain unknown in LPS-stimulated macrophages. Here, we investigated the anti-oxidizing effect of the dichloromethane (DCM) and hexane fractions from O. japonicus (OJD and OJH) against oxidative stress in RAW 264.7 cells stimulated by LPS. OJD and OJH significantly increased the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Additionally, it was found that the expression of HO-1 was stimulated by Nrf2 activated via degradation of Keap1. ERK and p38 inhibitors repressed HO-1 induced by OJD and OJH in LPS-stimulated cells, respectively. In conclusion, these results suggest that OJD and OJH may block oxidative damage stimulated by LPS, via increasing the expression of HO-1 and Nrf2, and MAPK signaling pathway. PMID- 24219868 TI - Alteration in cellular acetylcholine influences dauer formation in Caenorhabditis elegans. AB - Altered acetylcholine (Ach) homeostasis is associated with loss of viability in flies, developmental defects in mice, and cognitive deficits in human. Here, we assessed the importance of Ach in Caenorhabditis elegans development, focusing on the role of Ach during dauer formation. We found that dauer formation was disturbed in choline acetyltransferase (cha-1) and acetylcholinesterase (ace) mutants defective in Ach biosynthesis and degradation, respectively. When examined the potential role of G-proteins in dauer formation, goa-1 and egl-30 mutant worms, expressing mutated versions of mammalian G(o) and G(q) homolog, respectively, showed some abnormalities in dauer formation. Using quantitative mass spectrometry, we also found that dauer larvae had lower Ach content than did reproductively grown larvae. In addition, a proteomic analysis of acetylcholinesterase mutant worms, which have excessive levels of Ach, showed differential expression of metabolic genes. Collectively, these results indicate that alterations in Ach release may influence dauer formation in C. elegans. PMID- 24219869 TI - Sequence-specific interaction between ABD-B homeodomain and castor gene in Drosophila. AB - We have examined the effect of bithorax complex genes on the expression of castor gene. During the embryonic stages 12-15, both Ultrabithorax and abdominal-A regulated the castor gene expression negatively, whereas Abdominal-B showed a positive correlation with the castor gene expression according to real-time PCR. To investigate whether ABD-B protein directly interacts with the castor gene, electrophoretic mobility shift assays were performed using the recombinant ABD-B homeodomain and oligonucleotides, which are located within the region 10 kb upstream of the castor gene. The results show that ABD-B protein directly binds to the castor gene specifically. ABD-B binds more strongly to oligonucleotides containing two 5'-TTAT-3' canonical core motifs than the probe containing the 5' TTAC-3' motif. In addition, the sequences flanking the core motif are also involved in the protein-DNA interaction. The results demonstrate the importance of HD for direct binding to target sequences to regulate the expression level of the target genes. PMID- 24219871 TI - The public health value of doctors encouraging patients to exercise. PMID- 24219870 TI - Family caregivers of adults with acquired physical disability: Thai case-control study. AB - This case-control study compares the health of Thai family caregivers of adults with acquired physical disabilities with others without similar responsibilities. To ascertain health perceptions, face-to-face structured interviews using the Short Form (36) were conducted with participants randomly selected from primary care units in eastern Thailand (150 in each group). Despite similar sociodemographic profiles, caregivers reported more health problems and harmful health behaviours. Mean scores for physical and mental health were significantly lower. Factors contributing to poorer health among both caregivers and controls were older age, low educational level, insufficient income and existing health problems. Additional factors for caregivers were gender, spousal or in-law relationship, high dependency, long caregiving time, lack of previous experience and other caregiving responsibilities. This study identifies an urgent need for support to promote caregivers' health to enable them to maintain their vital role. PMID- 24219872 TI - Fabrication of liquid and vapor protective cotton fabrics. AB - Through microwave-assisted techniques, cotton textiles treated with heptadecafluoro-1,1,2,2-tetrahydrodecyltrimethoxysilane in the presence of high surface area silica nanoparticles create a material capable of repelling bulk liquid challenges while simultaneously adsorbing organic vapors from bulk liquid droplets. Characterizing the contradictory behavior of adsorption of vapors and repellency of liquids is the primary focus of this article. These procedures reveal a quick and simple method for a one-step deposition of a vapor-sorptive, liquid-repellent, Cassie-Baxter surface onto textiles. Packed column breakthrough and single swatch permeation experiments showed that treated materials possess a high affinity for 3-hepten-2-one vapor, while goniometry revealed contact angles in excess of 120 degrees for surface-deposited, 5 MUL droplets of several test liquids. Scanning electron micrograph images confirm a lotus-like, nanorough surface, while ATR-FTIR spectra confirm surface fluorocarbon moieties. The performance of so-treated materials lends itself to the application of chemical protective apparel, while the simplicity of the treatment bodes well for potential commercialization. PMID- 24219873 TI - Pulmonary function testing and chest tomography in patients with acromegaly. AB - BACKGROUND: Despite the gradual improvement in treatment procedures and cure rates of acromegaly, a steady increase in the mortality rate due to respiratory disease has been documented in recent decades. In this study, our objectives were to describe the abnormalities in lung structure and function that occur in acromegalic patients and to correlate these changes with hormonal levels. METHODS: This cross-sectional study included 20 acromegalic patients and 20 age and height-matched control subjects, all non-smokers. All subjects underwent spirometry, whole body plethysmography, carbon monoxide diffusing capacity, and respiratory muscle strength. Acromegalic patients also performed high-resolution computed tomography (HRCT). RESULTS: Most patients were female (65%), with a mean age of 52.5 +/- 13 years. Acromegalic patients showed lower values of maximum expiratory pressure (55.9 +/- 17.1 vs. 103.7 +/- 19.2%; p < 0.001) and maximum inspiratory pressure (71.4 +/- 27.8 vs. 85.3 +/- 24.1%; p = 0.005) compared to control subjects. The values of forced vital capacity (107.1 +/- 15.9 vs. 98.9 +/ 21.4%; p = 0.028), total lung capacity - TLC (107.3 +/- 12.9 vs. 93.7 +/- 7.60%; p = 0.002), residual volume (114.1 +/- 22.7 vs. 90.0 +/- 14.6%; p < 0.001), and airways' resistance (3.82 vs. 2.31 cmH2O/L/s; p = 0.039) were greater in acromegalic patients than in control subjects. The difference between the TLC measured by plethysmography and the VA (alveolar volume) measured during the DLCO maneuver was higher in acromegalic patients than in control subjects (0.69 +/- 0.46 vs. 0.19 +/- 0.61 L; p = 0.021). The main findings in HRCT in acromegalic patients were air trapping, airway calcification and bronchiectasis, which were observed in 60%, 40% and 35% of cases, respectively. There was no significant correlation between the levels of growth hormone and insulin-like growth factor I, the lung function and the air trapping. CONCLUSIONS: Acromegalic patients show changes consistent with the involvement of the small airways and ventilation inhomogeneity, both in terms of lung function and structure. However, air trapping cannot be explained either by hormone levels or changes in lung function. PMID- 24219874 TI - Relationship between poor physical function, inflammatory markers, and comorbidities in HIV-infected women on antiretroviral therapy. AB - BACKGROUND: HIV-infected individuals may be at increased risk of poor physical function. Chronic inflammation has been associated with decreased physical function in the elderly and may also influence physical function in HIV-infected individuals. METHODS: This cross-sectional study assessed physical function in 65 HIV-infected women aged 40 and older on stable antiretroviral treatment using the Short Physical Performance Battery (SPPB): a standardized test of balance, walking speed, and lower- extremity strength developed for elderly populations. The relationship between low SPPB score, selected demographic and medical characteristics, and high inflammatory biomarker profile was analyzed using Fisher's exact test and Wilcoxon rank sum test. RESULTS: The median age of subjects was 49 years (interquartile range [IQR] 45-55), and the median CD4 T cell count was 675 cells/mm(3) (IQR 436-828). Thirteen subjects (20%) had a low SPPB score. Subjects with a low SPPB score were more likely to be cigarette smokers (p=0.03), had more medical comorbidities (p=0.01), and had higher levels of interleukin-6 (IL-6) (p<0.05). They also tended to be older (median age 55 vs. 48, p=0.06), more likely to have diabetes (p=0.07), and have higher levels of soluble tumor necrosis factor-1 (p=0.09). CONCLUSIONS: Twenty percent of women aged 40 and older with well-treated HIV had poor physical-function performance, which was associated with the high burden of comorbidities in this population and with increased IL-6. However, it is unclear from this cross-sectional study whether increased inflammation was related to poor physical function or to other factors, such as age and medical comorbidities. PMID- 24219875 TI - Oxygen-driven anisotropic transport in ultra-thin manganite films. AB - Transition metal oxides have a range of unique properties due to coupling of charge, spin, orbital and lattice degrees of freedom and nearly degenerate multiple ground states. These properties make them interesting for applications and for fundamental investigations. Here we report a new phase with abnormal transport anisotropy in La(0.7)Sr(0.3)MnO3 ultra-thin films under large tensile strain. This anisotropy is absent in films under smaller tensile strain or compressive strain. Furthermore, thickness and magnetic-field-dependent experiments suggest that the tensile-strain-induced two-dimensional character is crucial for the observed phenomena. X-ray absorption spectroscopy results indicate that this anisotropy is likely driven by O 2p orbital, which hybridizes with Mn 3d. Ab initio calculations confirm this result. Our results may help to understand the anisotropic transport behaviour observed in other systems. PMID- 24219876 TI - Equivalence of quenched and annealed averaging in models of disordered polymers. AB - The equivalence of the influence of quenched and annealed disorder on the scaling properties of long flexible polymer chains is proved by analyzing the O(m) symmetric field theory in the polymer (de Gennes) limit m -> 0. Additional symmetry properties of the model in this limit are discussed. PMID- 24219877 TI - Improving care for the deteriorating child. PMID- 24219879 TI - Hypoactive sexual desire in women. AB - OBJECTIVE: This review aims to describe low sexual desire (1) as a construct within theoretical models of female sexual response, (2) as a sexual disorder with evolving or competing nosology between the DSM-IV-TR and the DSM 5, and (3) as a clinical condition that healthcare providers need to manage, and the current status of treatment options. METHODS: We conducted a literature review of the epidemiology, diagnosis, and treatment of low sexual desire/hypoactive sexual desire disorder (HSDD). RESULTS: The prevalence rate of low sexual desire is high, reaching 43%, whereas that of HSDD comes close to 10%. The DSM 5 categories of female sexual disorders include female sexual interest/arousal disorder, which is a combination of the DSM-IV-TR disorders HSDD and female sexual arousal disorder. Treatment paradigms vary and are individualized based on the biopsychosocial components of desire that are compromised in a woman. The two primary approaches to treating HSDD are psychotherapy/sex therapy (individual or couples) and pharmacotherapy. To date, there are no Food and Drug Administration approved pharmacologic treatments. However, four investigational drugs are in mid to late-stage clinical trial development. CONCLUSIONS: Low sexual desire is the most prevalent sexual problem in women and should be assessed and treated by healthcare professionals. Currently, there are only modest evidence-based nonpharmacologic treatment options and no approved pharmacologic options. Despite these treatment limitations, healthcare providers can address many of the sexual health concerns of women. PMID- 24219880 TI - Time is of the essence: personalized prediction of reproductive time span to optimize life goals. AB - CLINICAL SCENARIO: Regina is a 38-year-old woman who has been trying to conceive for about a year. She married late in life and started trying to conceive shortly thereafter. She is in good health, with no medical problems, and has had fairly regular menstrual cycles; however, she notes that the length of her cycle has gotten shorter over the past 2 to 3 months and is now occurring every 25 days. She has used an over-the-counter "fertility" test that assesses ovarian reserve by urinary follicle-stimulating hormone levels, which indicated that she has low fertility. She decided to seek medical help. PMID- 24219881 TI - Patient handout: What you should know about your reproductive time span. PMID- 24219882 TI - Health-related quality of life in women with or without hot flashes: a randomized placebo-controlled trial with hormone therapy. AB - OBJECTIVE: We assessed the impact of hot flashes and various forms of hormone therapy on health-related quality of life and sexual well-being in recently postmenopausal women. METHODS: We prospectively interviewed 150 healthy women about hot flashes and health-related quality of life (using the Women's Health Questionnaire and the McCoy Female Sexuality Questionnaire), menopause-related symptoms, and general health. The women were classified into those with (n = 72) and without (n = 78) hot flashes and treated for 6 months with transdermal estradiol (1 mg/d), oral estradiol (2 mg/d) with or without medroxyprogesterone acetate (5 mg/d), or placebo. RESULTS: At baseline, hot flashes contributed most strongly to poor sleep (correlation coefficient r = -0.525, P < 0.0001), somatic symptoms such as muscle pains (r = -0.348, P < 0.0001), menstrual cycle resembling complaints (r = -0.304, P < 0.0001), anxiety and fears (r = -0.283, P < 0.0001), decreased memory and concentration (r = -0.279, P = 0.001), and sexual behavior (r = -0.174, P = 0.035). The different hormone therapy regimens alleviated hot flashes equally effectively and were therefore combined into a single group for further analysis. In women with baseline flashes, hormone therapy use significantly improved the scores for sleep (0.787 [0.243] vs 0.557 [0.249], hormone therapy vs placebo, P = 0.001, at 6 mo), memory and concentration capacity (0.849 [0.228] vs 0.454 [0.301], P < 0.0001, at 6 mo), and anxiety and fears (0.942 [0.133] vs 0.826 [0.193], P = 0.005, at 6 mo). Hormone therapy use showed no significant impact on these variables in women without baseline flashes. CONCLUSIONS: Hot flashes contribute differently to various variables affecting health-related quality of life shortly after menopause. Estradiol or an estradiol-medroxyprogesterone acetate combination similarly alleviates hot flashes and improves health-related quality of life in relation to elimination of hot flashes. Hormone therapy use does not confer any detectable quality-of-life benefit over placebo in women without disturbing baseline flashes. PMID- 24219883 TI - Increased interleukin-17 in the cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease: a case-control study of rapidly progressive dementia. AB - BACKGROUND: Inflammatory responses in the cerebrospinal fluid (CSF) of patients with sporadic Creutzfeldt-Jakob disease (sCJD) remain elusive. METHODS: We conducted a case-control study, in which 14 patients with sCJD, 14 with noninflammatory neurological disorders, and 14 with autoimmune encephalitis were enrolled. We used the suspension array system to measure the concentrations of 27 cytokines in CSF. The cytokine titers of the three groups were compared, and the correlation between the relevant cytokine titers and clinical parameters was investigated in the patients with sCJD. RESULTS: Levels of the two cytokines interleukin (IL)-1 receptor antagonist and IL-17 were significantly elevated in the patients with sCJD compared with those in the patients with noninflammatory neurological disorders: IL-17 levels in sCJD were approximately ten times higher than in the noninflammatory neurological disorders (mean, 35.46 vs. 3.45 pg/ml; P < 0.001) but comparable to that in encephalitis (mean, 32.16 pg/ml). In contrast, levels of classical proinflammatory cytokines such as IL-12(p70) and tumor necrosis factor-alpha were increased only in encephalitis. Although not significant, IL-17 titers tended to be higher in the patients with shorter disease duration before CSF sampling (r = -0.452; P = 0.104) and in those with lower CSF total protein concentrations (r = -0.473; P = 0.086). CONCLUSIONS: IL 17 is significantly increased in CSF in sCJD, which can be an early event in the pathogenesis of sCJD. PMID- 24219884 TI - Natural products as starting points for the synthesis of complex and diverse compounds. AB - Covering: up to 2013. Natural products and their derivatives are used as treatments for numerous diseases. Many of these compounds are structurally complex, possessing a high percentage of sp(3) hybridized carbons and multiple stereogenic centers. Due to the difficulties associated with the isolation of large numbers of novel natural products, lead discovery efforts over the last two decades have shifted toward the screening of less structurally complex synthetic compounds. While there have been many success stories from these campaigns, the modulation of certain biological targets (e.g. protein-protein interactions) and disease areas (e.g. antibacterials) often require complex molecules. Thus, there is considerable interest in the development of strategies to construct large collections of compounds that mimic the complexity of natural products. Several of these strategies focus on the conversion of simple starting materials to value added products and have been reviewed elsewhere. Herein we review the use of natural products as starting points for the generation of complex compounds, discussing both early ad hoc efforts and a more recent systematization of this approach. PMID- 24219885 TI - Comparison of hospice use by European Americans, African Americans, and Latinos: a follow-up study. AB - This study investigated the rate of hospice use by Latinos and African Americans relative to their prevalence in the general population between 2004 and 2010 as a follow-up to a previous investigation. Archival data (N = 2625) were collected on patients' race/ethnicity, gender, marital status, length of stay in hospice, and reason for discharge. In contrast to previous findings, African Americans were more likely to utilize hospice services, but Latinos were less likely to use hospice services compared to the other groups. There were no differences among the racial/ethnic groups in terms of length of stay or disposition at termination. Strengthening efforts to reach a larger racial/ethnic representation in hospice programs may increase the rate of hospice use by some racial/ethnic groups but not others. PMID- 24219886 TI - Self-assembly of a set of hydrophilic-solvophobic-hydrophobic coil-rod-coil molecules based on perylene diimide. AB - The self-assembly and the resulting morphology of a set of asymmetrically substituted perylene diimide is discussed. We synthesized perylene diimides with hydrophilic Jeffamine(r) (PEO/PPO co-oligomer) attached to the imide nitrogen on one side and (hydrophobic) alkyl chains of different lengths on the other. Although studies on asymmetrically substituted perylene diimides have been reported by various authors, both side chains in this work are linear and we discuss the effect of the length of the hydrophobic alkyl side chain on the self assembly in water and aqueous mixtures and the resulting morphology. We find that self-assembly occurs in water in a range of concentrations (from 10(-7) to 10(-4) M), and the mode of packing of the H-stacked molecules changes with concentration for the propyl substitution. Although self-assembly does not occur in non-aqueous solvents such as acetone, it does upon addition of water. While other authors observed nano-belts and nano-fibers with asymmetrically substituted perylene diimides, the morphology of drop-cast films in our work consists of folded sheets and hollow tubes, of a few microns in diameter. Such folding in a non-chiral system such as the present case is attributed to predominant asymmetry of interactions between the molecules in the three directions, as we discussed in our previous work on an hydrogen bonded system (S. Khanna, M. K. Khan and P. Sundararajan, Langmuir, 2009, 25, 13183-13193). PMID- 24219887 TI - Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation. AB - BACKGROUND: Network inference from gene expression data is a typical approach to reconstruct gene regulatory networks. During chondrogenic differentiation of human mesenchymal stem cells (hMSCs), a complex transcriptional network is active and regulates the temporal differentiation progress. As modulators of transcriptional regulation, microRNAs (miRNAs) play a critical role in stem cell differentiation. Integrated network inference aimes at determining interrelations between miRNAs and mRNAs on the basis of expression data as well as miRNA target predictions. We applied the NetGenerator tool in order to infer an integrated gene regulatory network. RESULTS: Time series experiments were performed to measure mRNA and miRNA abundances of TGF-beta1+BMP2 stimulated hMSCs. Network nodes were identified by analysing temporal expression changes, miRNA target gene predictions, time series correlation and literature knowledge. Network inference was performed using NetGenerator to reconstruct a dynamical regulatory model based on the measured data and prior knowledge. The resulting model is robust against noise and shows an optimal trade-off between fitting precision and inclusion of prior knowledge. It predicts the influence of miRNAs on the expression of chondrogenic marker genes and therefore proposes novel regulatory relations in differentiation control. By analysing the inferred network, we identified a previously unknown regulatory effect of miR-524-5p on the expression of the transcription factor SOX9 and the chondrogenic marker genes COL2A1, ACAN and COL10A1. CONCLUSIONS: Genome-wide exploration of miRNA-mRNA regulatory relationships is a reasonable approach to identify miRNAs which have so far not been associated with the investigated differentiation process. The NetGenerator tool is able to identify valid gene regulatory networks on the basis of miRNA and mRNA time series data. PMID- 24219888 TI - Suppression of eukaryotic initiation factor 4E prevents chemotherapy-induced alopecia. AB - BACKGROUND: Chemotherapy-induced hair loss (alopecia) (CIA) is one of the most feared side effects of chemotherapy among cancer patients. There is currently no pharmacological approach to minimize CIA, although one strategy that has been proposed involves protecting normal cells from chemotherapy by transiently inducing cell cycle arrest. Proof-of-concept for this approach, known as cyclotherapy, has been demonstrated in cell culture settings. METHODS: The eukaryotic initiation factor (eIF) 4E is a cap binding protein that stimulates ribosome recruitment to mRNA templates during the initiation phase of translation. Suppression of eIF4E is known to induce cell cycle arrest. Using a novel inducible and reversible transgenic mouse model that enables RNAi-mediated suppression of eIF4E in vivo, we assessed the consequences of temporal eIF4E suppression on CIA. RESULTS: Our results demonstrate that transient inhibition of eIF4E protects against cyclophosphamide-induced alopecia at the organismal level. At the cellular level, this protection is associated with an accumulation of cells in G1, reduced apoptotic indices, and was phenocopied using small molecule inhibitors targeting the process of translation initiation. CONCLUSIONS: Our data provide a rationale for exploring suppression of translation initiation as an approach to prevent or minimize cyclophosphamide-induced alopecia. PMID- 24219890 TI - Mastication effects on the glycaemic index: impact on variability and practical implications. AB - Glycaemic variability challenges the accuracy and use of the glycaemic index (GI). The purpose of the current study was to determine the role of mastication on GI. Using a randomized, controlled, crossover, non-blind design, 15 healthy young subjects returned on 5 separate days for three glucose and two rice test sessions. At the rice sessions, subjects chewed each mouthful either 15 or 30 times. Rice chewed 15 times produced a total glycaemic response (GR; 155 mmol min/l), peak GR (2.4 mmol/l) and GI (68) significantly lower than when chewed for longer (30 times) (184 mmol min/l, 2.8 mmol/l and 88, respectively). The study shows that the GI of rice is affected by the degree of mastication. Chewing 15 times compared with 30 times significantly attenuates the GI, suggesting that mastication may potentially contribute to the glycaemic variability of rice. While future work must establish the extent and limits to which mastication affects glycaemia, it could also explore the potential of using mastication to reduce the glycaemic load of rice. PMID- 24219889 TI - Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy. AB - Previous microarray analyses indicated that a portion of the transcriptome in the macaque corpus luteum (CL) of the menstrual cycle was regulated indirectly by luteinizing hormone via the local actions of steroid hormones, notably progesterone (P). The current study was designed to investigate this concept in the CL of early pregnancy by analyzing chorionic gonadotrophin (CG)-regulated genes that are dependent versus independent of local steroid action. Exogenous human chorionic gonadotropin treatment simulating early pregnancy (SEP) began on Day 9 of the luteal phase in female rhesus monkeys with and without concurrent administration of the 3-beta-hydroxysteroid dehydrogenase inhibitor trilostane (TRL) with or without the synthetic progestin R5020. Compared with SEP treatment alone, TRL altered 50 mRNA transcripts on Day 10, rising to 95 on Day 15 (P<0.05, >=2-fold change in gene expression). Steroid-sensitive genes were validated; notably effects of steroid ablation and P replacement varied by day. Expression of some genes previously identified as P-regulated in the macaque CL during the menstrual cycle were not significantly altered by steroid ablation and P replacement during CG exposure in SEP. These data indicate that the majority of CG-regulated luteal transcripts are differentially expressed independently of local steroid actions. However, the steroid-regulated genes in the macaque CL may be essential during early pregnancy, based on previous reports that TRL treatment initiates premature structural regression of the CL during SEP. These data reinforce the concept that the structure, function and regulation of the rescued CL in early pregnancy differs from the CL of the menstrual cycle in primates. PMID- 24219891 TI - Plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, e-selectin and C-reactive protein levels in response to 4-week very-high-fructose or glucose diets. AB - BACKGROUND/OBJECTIVES: High intake of added sweeteners is considered to have a causal role in the pathogenesis of cardiometabolic disorders. Especially, high fructose intake is regarded as potentially harmful to cardiometabolic health. It may cause not only weight gain but also low-grade inflammation, which represents an independent risk factor for developing type 2 diabetes and cardiovascular disease. In particular, fructose has been suggested to induce plasminogen activator inhibitor-1 (PAI-1) expression in the liver and to increase circulating inflammatory cytokines. We therefore aimed to investigate, whether high-fructose diet has an impact on PAI-1, monocyte chemoattractant protein-1 (MCP-1), e selectin and C-reactive protein (CRP) concentrations in healthy humans. SUBJECTS/METHODS: We studied 20 participants (12 males and 8 females) of the TUebingen FRuctose Or Glucose study. This is an exploratory, parallel, prospective, randomized, single-blinded, outpatient, hypercaloric, intervention study. The participants had a mean age of 30.9 +/- 2.1 years and a mean body mass index of 26.0 +/- 0.5 kg/m(2) and they received 150 g of either fructose or glucose per day for 4 weeks. RESULTS: There were neither significant changes of PAI-1, MCP-1, e-selectin and CRP after fructose (n=10) and glucose (n=10) intervention nor treatment effects (all P>0.2). Moreover, we did not observe longitudinal associations of the inflammatory parameters with triglycerides, liver fat, visceral fat and body weight in the fructose group. CONCLUSIONS: Temporary high-fructose intake does not seem to cause inflammation in apparently healthy people in this secondary analysis of a small feeding trial. PMID- 24219892 TI - Maternal overweight impacts infant feeding patterns--the STEPS Study. AB - OBJECTIVES: We examined how maternal overweight impacts full breastfeeding (BF), total duration of BF and the age of introduction of complementary foods (CFs) and whether these have effect on children's growth from 0 to 2 years. SUBJECTS/METHODS: From 1797 families participating in the STEPS Study, 848 children had data on BF and anthropometric data at 13 months and 2 years of age and were included in this study. Data on BF and CFs were collected using a self administered follow-up diary. Information regarding maternal weight, height, pregnancy and delivery were received from maternity clinics and the National Longitudinal Census Files. The children's weight and length/height were recorded during the study visits at 13 months and 2 years. RESULTS: Overweight women breastfed fully (2.2 vs 2.8 months, P<0.0001) and totally (7.4 vs 9.0 months, P<0.0001) for a shorter time and introduced CFs earlier (4.1 vs 4.3 months, P=0.02) than normal weight women. Children of overweight women were heavier and had a higher body mass index at 2 years than children of normal weight women. At 2 years of age 30% of boys and 17% of girls were overweight or obese. However, children's obesity risk was not increased by maternal overweight (odds ratio (OR) 1.04, P=0.12). Longer duration of full BF (OR 0.86, P=0.04) and partial BF (OR 0.91, P=0.02) and delayed introduction of CFs (OR 0.69, P=0.03) were protective against obesity. CONCLUSIONS: Our study suggests that women who were overweight or obese before pregnancy breastfed for a shorter time and introduced CFs earlier than normal weight women, which may further impact children's growth. PMID- 24219893 TI - Isotopic estimates of sugar intake are related to chronic disease risk factors but not obesity in an Alaska native (Yup'ik) study population. AB - BACKGROUND/OBJECTIVES: Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup'ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model. This study tested associations of isotopic estimates of sugar intake with body mass index (BMI), waist circumference (WC) and a broad array of other physiological and biochemical measures of chronic disease risk in Yup'ik people. SUBJECTS/METHODS: In a cross-sectional sample of 1076 Yup'ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors. RESULTS: Isotopic estimates of sugar intake were not associated with BMI (P=0.50) or WC (P=0.85). They were positively associated with blood pressure, triglycerides (TG) and leptin, and are inversely associated with total-, high-density lipoprotein- and low-density lipoprotein-cholesterol and adiponectin. CONCLUSIONS: Isotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup'ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup'ik people; however, longitudinal studies are required to understand associations with chronic disease incidence. PMID- 24219894 TI - Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach. AB - BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. SUBJECTS/METHODS: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994. RESULTS: In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, P<0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was -1.51, 95% CI: -5.80, 2.98, P=0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: 3.67, 95.20, P=0.080). CONCLUSIONS: The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm a causal relationship. PMID- 24219895 TI - Dietary intake of patients with angiographically defined coronary artery disease and that of healthy controls in Iran. AB - OBJECTIVE: The aim of this study was to investigate the relationship between dietary intake and biomarkers of cardiovascular risk in individuals with and without angiographically defined coronary artery disease. SUBJECTS/METHODS: Coronary angiography was undertaken in 445 individuals who were divided into those with significant disease (>50% occlusion) (Angio+ (n=273)) and those with <50% coronary artery occlusion (Angio- (n=172)). Apparently healthy, non symptomatic individuals (n=443) were considered as the control group. Dietary intake was assessed using a 24-h dietary recall method and dietary analysis was performed using Diet Plan 6 software. RESULTS: Concentrations of starch, saturated fatty acids, polyunsaturated fatty acids, magnesium, iron and copper in the control group were less than those in the other groups (P<0.05), but after adjusting for total energy intake these differences were no longer apparent. The mean intake of protein, cholesterol, phosphorus, zinc, zinc/copper ratio, selenium, iodine, carotene, vitamin E, niacin, pantothene and pyridoxine was less in the control group compared with the other two groups (P<0.05), and the mean of sugar, fiber, transfatty acids, manganese, folate and vitamin C was higher in the control group than in other groups (P<0.05). Lipid profile values between the three groups did not differ significantly. CONCLUSIONS: These results indicate that the amount of intake of various nutrients can be considered as an independent risk factor for CAD. Further research on the relationship between CAD and nutrient intake, especially intake of essential micronutrients, is needed. PMID- 24219897 TI - Janus cyclic peptide-polymer nanotubes. AB - Self-assembled nanotubular structures have numerous potential applications but these are limited by a lack of control over size and functionality. Controlling these features at the molecular level may allow realization of the potential of such structures. Here we report a new generation of self-assembled cyclic peptide polymer nanotubes with dual functionality in the form of either a Janus or mixed polymeric corona. A 'relay' synthetic strategy is used to prepare nanotubes with a demixing or mixing polymeric corona. Nanotube structure is assessed in solution using (1)H-(1)H nuclear Overhauser effect spectroscopy NMR, and in bulk using differential scanning calorimetry. The Janus nanotubes form artificial pores in model phospholipid bilayers. These molecules provide a viable pathway for the development of intriguing nanotubular structures with dual functionality via a demixing or a mixing polymeric corona and may provide new avenues for the creation of synthetic transmembrane protein channel mimics. PMID- 24219896 TI - Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease. AB - This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception. PMID- 24219898 TI - Decentralised paediatric HIV care in Ethiopia: a comparison between outcomes of patients managed in health centres and in a hospital clinic. AB - BACKGROUND: In order to increase access to antiretroviral therapy (ART) in HIV infected children, paediatric HIV care has been introduced in health centres in Ethiopia, where patients are managed by health professionals with limited training. OBJECTIVE: To compare outcomes of paediatric HIV care in hospital and health centre clinics and to determine risk factors for death and loss to follow up (LTFU). DESIGN: Retrospective comparison of patient characteristics and outcomes among children managed in a public hospital and all five public health centres in the uptake area. RESULTS: Among 1,960 patients (health centres 572, hospital clinic 1,388), 34% were lost to follow-up, 2% died, 14% were transferred out, and 46% remained in care. Children initiating ART in the hospital clinic had lower median CD4 cell counts (age <1 year: 575 vs. 1,183 cells/mm3, p=0.024; age 1-5 years: 370 vs. 598 cells/mm3, p<0.001; age >5 years: 186 vs. 259 cells/mm3, p<0.001), and a higher proportion were <1 year of age (22% vs. 15%, p=0.025). ART initiation rates and retention in care were similar between children managed in health centres and in the hospital clinic (36% vs. 37% and 47% vs. 46%, respectively). Among patients starting ART, mortality was associated with age <1 year [hazard ratio (HR) 12.0; 95% confidence interval (CI): 3.5, 41]. LTFU was associated with CD4 cell counts <350 cells/mm3 (HR 1.8; 95% CI: 1.2, 3.0), weight for-age z-scores below -4 (HR 2.8; 95% CI: 1.4, 5.6), and age <5 years (1-5 years: HR 1.6; 95% CI: 1.0, 2.5; <1 year: HR 3.3; 95% CI: 1.6, 6.6). CONCLUSIONS: Outcomes of HIV care were similar for Ethiopian children managed in a hospital clinic or in health centres. However, patients treated at the hospital clinic had characteristics of more advanced disease. Rates of LTFU were high in both types of health facility. PMID- 24219899 TI - Primary stability of an intramedullary calcaneal nail and an angular stable calcaneal plate in a biomechanical testing model of intraarticular calcaneal fracture. AB - BACKGROUND: Nowadays, open anatomic reduction and internal fixation can be considered as a valuable treatment for displaced intra-articular fractures of the calcaneus. However, the application of a calcaneal plate via an extensile lateral approach is at risk for a substantial rate of complications including delayed healing, skin necrosis, or infection. There is some evidence that a limited exposure might contribute to a decreased soft tissue complication rate bearing in mind that most minimally invasive techniques have to accept a reduced primary stability compared with the open application of an angular stable plate. Recently, an intrafocal minimal invasive reduction technique has been established employing an intramedullary nail for fracture stabilisation and support of the subtalar joint. The aim of this study was to compare the primary biomechanical performance of the new device versus lateral angular stable plating. MATERIAL AND METHODS: Biomechanical testings were performed on 14 human cadaveric feet (7 pairs). Dry calcaneal bones were fractured resulting in a Sanders type IIB fracture pattern and fixed by either a calcaneal locking plate or an intramedullary calcaneal nail. Compressive testing via the corresponding talus was employed at a constant loading velocity until failure with an universal testing machine and a specific mounting device to avoid any shear forces. Apart from the data of the load deformation diagram the relative motion of the fracture elements during loading was recorded by 8 extensometric transducers. After failure the specimens were carefully examined to check the failure patterns. RESULTS: The displacement of the subtalar joint fragment was substantially lower in specimens fixed with the nail. Stiffness and load to failure were significantly higher after fixation with the intramedullary nail than after application of the angular stable plate. Failure with both fixation modes generally occurred at the anterior calcaneal process fragment. CONCLUSIONS: The primary stability of an intramedullary nail appeared to be superior to an angular stable plate representing the present standard technique in open reconstruction of the fractured calcaneus. The results from the experimental model speak in favour of the clinical use of the intramedullary calcaneal nail. PMID- 24219900 TI - A survey of trauma database utilisation in England. AB - Trauma registries are used worldwide to coordinate patient care as well as provide data for audit and research purposes. National registries collect this data, producing research opportunities, outcome standards and a means by which to benchmark trauma centre performance. The Trauma Audit and Research Network (TARN) is the UK national registry, with data upload being mandatory from all major trauma centres (MTCs), a process which is manual and time and resource intensive. A telephone survey was carried out to collect data from all 26 MTCs in England. A questionnaire was designed to identify how data was collected at a local level, what software and methods were used and what resources were allocated to collect and upload trauma data to the TARN. Further information on hospital size and number of beds was collected from internet searches. Twenty-three MTCs were contacted in total. The majority used Microsoft Excel, with the next most common programme being Bluespier. Other commercially available registries used included Collector, VTOMS and McKesson. One trust created its own software and three used no electronic database at all. Electronic patient record integration was variable and limited to some commercially available registries. The mean number of TARN data collectors was two per centre, with a mean duration of data collection of 4.5 years. The wide range of software options and their lack of integration with the hospital electronic patient records results in the duplication of data as well as requiring time and resources. This may also be due to the difference in data required for coordinating on-going patient care and that required for upload to the TARN. Whilst some of these programmes do have the capabilities for automatic data upload, further efforts must be made to provide a cohesive system that provides the required integration and customisability in order to improve efficiency and ultimately trauma care. PMID- 24219901 TI - Determinants of limitations in unpaid work after major trauma: a prospective cohort study with 15 months follow-up. AB - OBJECTIVE: To identify determinants of limitations in unpaid work (household work, shopping, caring for children and odd jobs around the house) in patients who had suffered major trauma (ISS>=16) and who were in full-time employment (>=80%) at the time of injury. DESIGN: Prospective cohort study. SETTING: University Medical Centre Utrecht, a level 1 trauma centre in the Netherlands. METHOD: All severely injured (ISS>=16) adult (age>=16) trauma survivors admitted from January 1999 to December 2000 who were full-time employed at time of the injury were invited for follow-up (n=214). Outcome was assessed with the 'Health and Labour Questionnaire' (HLQ) at a mean of 15 months (SD=1.5) after injury. The HLQ was completed by 211 patients. RESULTS: Response rate was 93%. Logistic regression analyses identified the percentage of permanent impairment (% PI), level of participation (RtW), co-morbidity, lower extremity injury (LEI) and female gender as determinants of limitations in unpaid work. Patients with a post injury status of part-time or no return to work experienced more limitations in unpaid work than those who returned to full-time employment. CONCLUSIONS: Resuming paid work after major trauma is not associated with reductions in unpaid activities. To assess the long-term outcome of rehabilitation programmes, we recommend a measure that combines patient's satisfaction in their post-injury jobs with a satisfactory level of activities in their private lives. PMID- 24219902 TI - Interrupting my shift: disaster preparedness and response. PMID- 24219903 TI - Clinical utility of screening laboratory tests in pediatric psychiatric patients presenting to the emergency department for medical clearance. AB - STUDY OBJECTIVE: We assess whether screening laboratory tests obtained to medically clear pediatric psychiatric patients altered management or disposition. METHODS: This was a retrospective chart review of consecutive patients younger than 18 years and presenting to an academic pediatric emergency department for medical clearance of an acute psychiatric emergency potentially requiring an involuntary hold (danger to self, danger to others, grave disability) from July 2009 to December 2010. Patients were identified by discharge diagnosis codes. History and physical examination and screening laboratory tests were reviewed for changes in management or disposition. Further analysis compared length of stay according to type of laboratory test performed. To avoid missing patients presenting with or for evaluation of an involuntary hold for whom an organic cause was diagnosed, charts with psychiatric chief complaints were reviewed for the same period. RESULTS: One thousand eighty-two visits resulting in 13,725 individual laboratory tests were analyzed. Of 871 visits with laboratory tests performed, abnormal laboratory tests were associated with 7 disposition changes (0.8%) and 50 management changes (5.7%) not associated with a disposition change. Twenty-five patients with noncontributory history and physical examination results had management changes, all non-urgent. One patient with a noncontributory history and physical examination result had a disposition changing laboratory result, a positive urine pregnancy test. Patients who had any screening test performed had a longer length of stay than patients without testing (117 minutes longer; 95% confidence interval 109.7 to 124.4 minutes). In charts reviewed according to chief complaint, no patient was found to have an organic cause of their symptoms according to only screening tests. CONCLUSION: Screening laboratory tests resulted in few management and disposition changes in patients with noncontributory history and physical examination results but were associated with increased length of stay. PMID- 24219904 TI - Short range order in liquid pnictides. AB - Liquid pnictides have anomalous physical properties and complex radial distribution functions. The quasi-crystalline model of liquid structure is applied to interpret the three-dimensional structure of liquid pnictides. It is shown that all the column V elements can be characterized by a short range order lattice symmetry similar to that of the underlying solid, the A7 structure, which originates from a Peierls distorted simple cubic lattice. The evolution of the liquid structure down the column as well as its temperature and pressure dependence is interpreted by means of the effect of thermodynamic parameters on the Peierls distortion. Surprisingly, it is found that the Peierls effect increases with temperature and the nearest neighbour distances exhibit negative thermal expansion. PMID- 24219905 TI - Pre-conditioning mesenchymal stromal cell spheroids for immunomodulatory paracrine factor secretion. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) exhibit the inherent potential to regulate multiple signaling pathways and cell types that contribute to the pathogenesis of inflammatory and immune diseases. However, more recent studies have suggested that the secretion of immunomodulatory factors by MSCs can be enhanced by three-dimensional aggregation or pro-inflammatory cytokine treatment. METHODS: Human MSC spheroids were formed by forced aggregation into agarose micro wells and subsequently cultured in either minimal essential medium alpha supplemented with fetal bovine serum or serum-free, defined MesenCult-XF medium (STEMCELL Technologies, Vancouver, Canada). A subset of the spheroids were treated with pro-inflammatory cytokines interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha or both for 4 days. Immunomodulatory factor (prostaglandin E2, indoleamine 2,3-dioxygenase, transforming growth factor-beta1 and interleukin-6) secretion was quantified after 4 days of culture, and the immunomodulatory activity of MSCs was assessed by quantifying activated macrophage expression of TNF-alpha after trans-well co-culture. RESULTS: Culturing human MSCs as three dimensional aggregates increased secretion of immunomodulatory paracrine factors, which was enhanced further by treatment with IFN-gamma and TNF-alpha, demonstrating that these parameters can synergistically enhance endogenous human MSC immunomodulatory properties. However, immunomodulatory factor secretion was found to be highly dependent on the composition of cell culture medium. Human MSCs cultured in MesenCult-XF medium displayed significantly less expression of prostaglandin E2, indoleamine 2,3-dioxygenase, transforming growth factor-beta1 and interleukin-6 compared with human MSCs cultured in medium supplemented with fetal bovine serum. Finally, pre-conditioning of human MSC spheroids with IFN gamma and TNF-alpha resulted in greater immunomodulatory activity in a macrophage co-culture assay. CONCLUSIONS: Altogether, engineering the environment of human MSCs to develop pre-conditioning strategies for enhancing human MSC immunomodulation may be a simple approach for improving MSC-based therapies for the treatment of inflammatory and immune diseases. PMID- 24219906 TI - Magnetic resonance and near-infrared imaging using a novel dual-modality nano probe for dendritic cell tracking in vivo. AB - BACKGROUND AIMS: The effect of cellular-based immunotherapy is highly correlated with the success of dendritic cells (DCs) homing to the draining lymph nodes (LNs) and interacting with antigen-specific CD4(+) T cells. In this study, a novel magneto-fluorescent nano-probe was used to track the in vivo migration of DCs to the draining LNs. METHODS: A dual-modality nano-probe composed of superparamagnetic iron oxide (SPIO) and near-infrared fluorescent (NIRF) dye (NIR797) was developed, and its magnetic and optical contrasting properties were characterized. DCs generated from mouse bone marrow were co-cultured with the probe at a lower concentration of 10 MUg/mL. The cell phenotype and function of DCs were also investigated by fluorescence-activated cell sorting analysis and mixed leukocyte reactivity assay. Labeled DCs were injected into the footpad of C57BL/6 mice. Afterward, magnetic resonance imaging, NIRF imaging, Perls staining and CD11c immunofluorescence were used to observe the migration of the labeled DCs into draining LNs. RESULTS: The synthetic SPIO-NIR797 nano-probe had a desirable superparamagnetic and near-infrared behavior. Perls staining showed perfect labeling efficiency. The cell phenotypes, including CD11c, CD80, CD86 and major histocompatibility complex class II, as well as the T-cell activation potential of the mature DCs were insignificantly affected after incubation (P > 0.05). Labeled DCs migrating into LNs could be detected by both magnetic resonance imaging and NIRF imaging simultaneously, which was further confirmed by Perls staining and immunofluorescence. CONCLUSIONS: The novel dual-modality SPIO NIR797 nano-probe has highly biocompatible characteristics for labeling and tracking DCs, which can be used to evaluate cancer immunotherapy in clinical applications. PMID- 24219907 TI - Oxidative stress, metalloproteinase and LDH in children with intractable and non intractable epilepsy as reflected in salivary analysis. AB - Oxidative stress and metalloproteinase (MMPs) may have a pivotal role in the pathogenesis of epilepsy. This study examined the underlying mechanism of epilepsy in children and especially in its intractable form, with respect to the roles of MMP's and free radicals in general and in saliva in particular. We also explored the possible diagnostic role of a compositional salivary analysis in these children, as salivary collection is simple, non-invasive (and thus 'children-friendly') and requires almost no expertise. We analyzed saliva parameters of 33 epileptic children: 22 with non-intractable (E's) and 11 with intractable epilepsy (IE's), and compared them with 16 healthy controls. Mean salivary LDH concentration in controls was 213.1+/-34.0IU/L, dropping by 38% (p=0.014) in E's and by 76% (p=0.0003) in IE's. Mean salivary values of peroxidase activity, SOD activity and carbonyls level were 480+/-14mU/mL, 1.30+/ 0.15U/mL and 0.34+/-0.04nmol/mg, respectively, in controls, increasing by 6% (p=0.03), by 37% (p=0.04) and by 59% (p=0.003) in E's, and by 10% (p=0.02), by 29% (p=0.03) and by 56% (p=0.004) in IE's. Mean salivary MMP 9 concentration was 0.062+/-0.003 (OD) in controls, decreased by 12% (p=0.048) in E's, and by 23%, (p=0.009) in IE's. Our results enhance our understanding of epilepsy's biological underlying mechanism as reflected in the saliva of children with both intractable and non intractable disease. SIGNIFICANCE: The currently reported salivary analysis and the demonstrated salivary alterations in children suffering from epilepsy represent a novel direction. We found various salivary alterations demonstrated in the general composition as well as the oxidative and metalloproteinase analyses and more so in the intractable epilepsy group than in the non intractable epilepsy group. Hence, salivary oxidative components and MMP levels were found useful in the detection and follow-up of children with epilepsy. As such, we recommend using this non-invasive salivary analysis for diagnosis and monitoring of epileptic activity in children. PMID- 24219908 TI - Contribution of oligomerization to the anti-HIV-1 properties of SAMHD1. AB - BACKGROUND: SAMHD1 is a restriction factor that potently blocks infection by HIV 1 and other retroviruses. We have previously demonstrated that SAMHD1 oligomerizes in mammalian cells by immunoprecipitation. Here we investigated the contribution of SAMHD1 oligomerization to retroviral restriction. RESULTS: Structural analysis of SAMHD1 and homologous HD domain proteins revealed that key hydrophobic residues Y146, Y154, L428 and Y432 stabilize the extensive dimer interface observed in the SAMHD1 crystal structure. Full-length SAMHD1 variants Y146S/Y154S and L428S/Y432S lost their ability to oligomerize tested by immunoprecipitation in mammalian cells. In agreement with these observations, the Y146S/Y154S variant of a bacterial construct expressing the HD domain of human SAMHD1 (residues 109-626) disrupted the dGTP-dependent tetramerization of SAMHD1 in vitro. Tetramerization-defective variants of the full-length SAMHD1 immunoprecipitated from mammalian cells and of the bacterially-expressed HD domain construct lost their dNTPase activity. The nuclease activity of the HD domain construct was not perturbed by the Y146S/Y154S mutations. Remarkably, oligomerization-deficient SAMHD1 variants potently restricted HIV-1 infection. CONCLUSIONS: These results suggested that SAMHD1 oligomerization is not required for the ability of the protein to block HIV-1 infection. PMID- 24219909 TI - Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. AB - Monocytes/macrophages are heterogeneous and versatile cells that could undergo their phenotypically/functionally dynamic switch in response to the microenvironment signals. Two major macrophage subpopulations with different functions which represent extreme of a continuum in a universe of activation states, including classically activated/inflammatory (M1) and alternatively activated/regenerative (M2) macrophages, have long been recognized. Emerging evidence through genetic or pharmacologic approaches has now been made in defining the actual fate in vivo and in vitro underlying M1 or M2-like polarized activation under physiological and pathological conditions. These cells are characterized by their expression of cell surface markers, secreted cytokines and chemokines, and transcription and epigenetic pathways. Here in this review, we shed new light on the contribution of several major signaling pathways and their modulators/targets involved in directing the macrophage plasticity and polarized function, assess the mechanisms of macrophage polarization by interacting endogenous cellular mechanisms and molecules associated with reciprocal skewing of macrophage polarization between the M1 and M2 states. The identification of mechanisms underlying functional polarization of macrophages into M1 or M2 cells might provide new insights into a basis for macrophage-centered diagnostic and therapeutic strategies for multiple diseases. PMID- 24219911 TI - Life expectancy at birth and at age 65 for local areas in England and Wales. PMID- 24219910 TI - Evidence for a regulatory role of Cullin-RING E3 ubiquitin ligase 7 in insulin signaling. AB - Dysfunctional regulation of signaling pathways downstream of the insulin receptor plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. In this study we report both in vitro and in vivo experimental evidence for a role of Cullin-RING E3 ubiquitin ligase 7 (CRL7) in the regulation of insulin signaling and glucose homeostasis. We show that Cul7(-/-) mouse embryonic fibroblasts displayed enhanced AKT and Erk MAP kinase phosphorylation upon insulin stimulation. Depletion of CUL7 by RNA interference in C2C12 myotubes led to increased activation of insulin signaling pathways and cellular glucose uptake, as well as a reduced capacity of these cells to execute insulin-induced degradation of insulin receptor substrate 1 (IRS1). In vivo, heterozygosity of either Cul7 or Fbxw8, both key components of CRL7, resulted in elevated PI3 kinase/AKT activation in skeletal muscle tissue upon insulin stimulation when compared to wild-type controls. Finally, Cul7(+/-) or Fbxw8(+/-) mice exhibited enhanced insulin sensitivity and plasma glucose clearance. Collectively, our findings point to a yet unrecognized role of CRL7 in insulin-mediated control of glucose homeostasis by restraining PI3 kinase/AKT activities in skeletal muscle cells. PMID- 24219912 TI - Risk factors for acute decompensation of chronic kidney disease in hospitalized patients in the nephrology department: a case-control study. AB - OBJECTIVE: To investigate risk factors for acute kidney injury (AKI) in hospitalized patients with chronic kidney disease (CKD) a case-control study was conducted in the Nephrology Department of Hedi Chaker University Hospital in Sfax, Tunisia, for a 1-year period. METHODS: All patients with baseline renal insufficiency hospitalized for AKI were considered as cases. They were compared with control patients with CKD. A conditional logistic regression model was used to identify independent risk factors for AKI in patients with CKD. RESULTS: A total of 58 cases were compared with 114 control subjects. In multivariable models, baseline diabetes, cardiopathy disease, and exposure to non-steroidal anti-inflammatory drugs were independent risk factors for AKI in patients with CKD. However, exposure to calcium channel blockers (CCBs) was associated with decreased risk for AKI on CKD (OR = 0.4; CI 95%: 0.2 - 0.8, p = 0.007). CONCLUSIONS: Patients with CKD may benefit from more aggressive cardiovascular screening to prevent episodes of acute kidney injury. More efforts should be made to prevent prescription drug abuse and to demonstrate the role of CCBs in renal protection in these patients. PMID- 24219913 TI - Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study. AB - BACKGROUND: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. METHODS: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 - 74 years with mild-to moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score <= 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. RESULTS: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m2); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p <= 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 - 2.03) and lower eGFR (beta -2.47, p = 0.03). CONCLUSION: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD. PMID- 24219915 TI - Morphological awareness and reading difficulties in adolescent Spanish-speaking language minority learners and their classmates. AB - This study investigated the role of morphological awareness weaknesses in the reading difficulties encountered by Spanish-speaking language minority learners and their native English-speaking peers in sixth grade. One hundred and thirty eight students (82 language minority learners; 56 native English speakers) were assessed on English measures of reading comprehension, silent word reading fluency, and derivational morphological awareness. Students with specific reading comprehension difficulties, specific word reading difficulties, and combined difficulties were identified using categorical cut-scores. Findings indicated that morphological awareness differentiated skilled readers from students with reading difficulties. Substantial proportions of students with reading difficulties (38%-63%, depending on reading difficulty subtype) demonstrated weaknesses in morphological awareness. Language minority learners with reading difficulties were particularly likely to demonstrate weaknesses in morphological awareness (55%-64%), compared to native English speakers with similar reading difficulties (13%-50%). Findings suggest the diagnostic potential of morphological awareness for adolescent learners with reading difficulties, especially those from language minority backgrounds. PMID- 24219914 TI - Multisyllabic word reading as a moderator of morphological awareness and reading comprehension. AB - The purpose of this study was to investigate whether the relation between morphological awareness on reading comprehension is moderated by multisyllabic word reading ability in fifth-grade students (N = 169, 53.7% female, 65.2% minority status, 69.2% free/reduced lunch status), oversampled for poor reading skill, when controlling for general knowledge and vocabulary. Based on the lexical quality hypothesis, it was expected that morphological awareness would have a stronger effect on comprehension for children with poor word reading skills, suggesting possible use of morphological awareness for word identification support. Results indicated that neither morphological awareness nor word reading was uniquely associated with reading comprehension when both were included in the model along with vocabulary and general knowledge. Instead, the interaction between word reading and morphological awareness explained significant additional variance in reading comprehension. By probing this interaction, it was determined that the effect of morphological awareness on reading comprehension was significant for the 39% of the sample that had more difficulty reading multisyllabic words but not for students at the higher end of the multisyllabic word reading continuum. We conclude from these results that the relation between morphological awareness and reading comprehension is moderated by multisyllabic word reading ability, providing support for the lexical quality hypothesis. Although we have only correlational data, we suggest tentative instructional practices for improving the reading skill of upper elementary struggling readers. PMID- 24219916 TI - The representation of roots in the spelling of children with specific language impairment. AB - Children with Specific Language Impairment (SLI) have demonstrated general spelling and writing difficulties. We investigated the sensitivity of children with SLI to the consistent spelling of root morphemes, a feature to which young typically developing children demonstrate sensitivity. We asked children with SLI and two groups of typically developing children (n = 17 in each group) to spell the same letter-sound sequence (e.g., win) as a root, and as a component of inflected, derived, and control words (e.g., win, wins, winner, wink). Children with SLI and spelling-age-matched children (mean age of 9 and 7 years, respectively) were more accurate and more consistent in spelling the initial sections of the inflected and derived words than of the control words, a pattern that suggests sensitivity to the representation of roots in spelling. The absence of a group-level interaction suggests comparable sensitivity in the two groups. Our results suggest that elementary-school-aged children with SLI are sensitive to the consistent spelling of roots, at least to the extent predicted by their general spelling abilities. PMID- 24219917 TI - Morphological knowledge and literacy acquisition. AB - The purpose of this special issue of the Journal of Learning Disabilities is to bring to the attention of researchers and educators studies on morphology and literacy that either involve students with learning difficulties or have educational implications for teaching such students. In our introduction, we first provide background information about morphological knowledge and consider the role of morphology in literacy, focusing on findings that are relevant for instruction of students who struggle with reading and writing. Next we present an overview of the studies included in this issue, organized by current issues concerning the role of morphological knowledge in literacy. Collectively, the articles in this issue suggest that students with weaker literacy skills tend to lag behind their peers in morphological knowledge but that all students are likely to benefit from morphological instruction. Morphological interventions hold promise, especially for students who face challenges in language learning and literacy, but additional research is needed to provide a basis for informed decisions about the design of effective morphological interventions. PMID- 24219918 TI - Shape constancy measured by a canonical-shape method. AB - Shape constancy is the ability to perceive that a shape remains the same when seen in different orientations. It has usually been measured by asking subjects to match a shape in the frontal plane with an inclined shape. But this method is subject to ambiguity. In Experiment 1 we used a canonical-shape method, which is not subject to ambiguity. Observers selected from a set of inclined trapezoids the one that most resembled a rectangle (the canonical shape). This task requires subjects to register the linear perspective of the image, and the distance and inclination of the stimulus. For inclinations of 30 degrees and 60 degrees and distances up to 1m, subjects were able to distinguish between a rectangle and a trapezoid tapered 0.4 degrees . As the distance of the stimulus increased to 3m, linear perspective became increasingly perceived as taper. In Experiment 2 subjects matched the perceived inclination of an inclined rectangle, in which the only cue to inclination was disparity, to the perceived inclination of a rectangle with all depth cues present. As the distance of the stimulus increased, subjects increasingly underestimated the inclination of the rectangle. We show that this pattern of inclination underestimation explains the distance-dependent bias in taper judgments found in Experiment 1. PMID- 24219919 TI - Differential up-regulation of Vesl-1/Homer 1 protein isoforms associated with decline in visual performance in a preclinical glaucoma model. AB - Glaucoma is a multifactorial progressive ocular pathology, clinically presenting with damage to the retina and optic nerve, ultimately leading to blindness. Retinal ganglion cell loss in glaucoma ultimately results in vision loss. Vesl/Homer proteins are scaffolding proteins that are critical for maintaining synaptic integrity by clustering, organizing and functionally regulating synaptic proteins. Current anti-glaucoma therapies target IOP as the sole modifiable clinical parameters. Long-term pharmacotherapy and surgical treatment do not prevent gradual visual field loss as the disease progresses, highlighting the need for new complementary, alternative and comprehensive treatment approaches. Vesl/Homer expression was measured in the retinae of DBA/2J mice, a preclinical genetic glaucoma model with spontaneous mutations resulting in a phenotype reminiscent of chronic human pigmentary glaucoma. Vesl/Homer proteins were differentially expressed in the aged, glaucomatous DBA/2J retina, both at the transcriptional and translational level. Immunoreactivity for the long Vesl 1L/Homer 1c isoform, but not of the immediate early gene product Vesl-1S/Homer 1a was increased in the synaptic layers of the retina. This increased protein level of Vesl-1L/Homer 1c was correlated with phenotypes of increased disease severity and a decrease in visual performance. The increased expression of Vesl-1L/Homer 1c in the glaucomatous retina likely results in increased intracellular Ca(2+) release through enhancement of synaptic coupling. The ensuing Ca(2+) toxicity may thus activate neurodegenerative pathways and lead to the progressive loss of synaptic function in glaucoma. Our data suggest that higher levels of Vesl 1L/Homer 1c generate a more severe disease phenotype and may represent a viable target for therapy development. PMID- 24219920 TI - ABC transporter activity linked to radiation resistance and molecular subtype in pediatric medulloblastoma. AB - BACKGROUND: Resistance to radiation treatment remains a major clinical problem for patients with brain cancer. Medulloblastoma is the most common malignant brain tumor of childhood, and occurs in the cerebellum. Though radiation treatment has been critical in increasing survival rates in recent decades, the presence of resistant cells in a substantial number of medulloblastoma patients leads to relapse and death. METHODS: Using the established medulloblastoma cell lines UW228 and Daoy, we developed a novel model system to enrich for and study radiation tolerant cells early after radiation exposure. Using fluorescence activated cell sorting, dead cells and cells that had initiated apoptosis were removed, allowing surviving cells to be investigated before extensive proliferation took place. RESULTS: Isolated surviving cells were tumorigenic in vivo and displayed elevated levels of ABCG2, an ABC transporter linked to stem cell behavior and drug resistance. Further investigation showed another family member, ABCA1, was also elevated in surviving cells in these lines, as well as in early passage cultures from pediatric medulloblastoma patients. We discovered that the multi-ABC transporter inhibitors verapamil and reserpine sensitized cells from particular patients to radiation, suggesting that ABC transporters have a functional role in cellular radiation protection. Additionally, verapamil had an intrinsic anti-proliferative effect, with transient exposure in vitro slowing subsequent in vivo tumor formation. When expression of key ABC transporter genes was assessed in medulloblastoma tissue from 34 patients, levels were frequently elevated compared with normal cerebellum. Analysis of microarray data from independent cohorts (n = 428 patients) showed expression of a number of ABC transporters to be strongly correlated with certain medulloblastoma subtypes, which in turn are associated with clinical outcome. CONCLUSIONS: ABC transporter inhibitors are already being trialed clinically, with the aim of decreasing chemotherapy resistance. Our findings suggest that the inhibition of ABC transporters could also increase the efficacy of radiation treatment for medulloblastoma patients. Additionally, the finding that certain family members are associated with particular molecular subtypes (most notably high ABCA8 and ABCB4 expression in Sonic Hedgehog pathway driven tumors), along with cell membrane location, suggests ABC transporters are worthy of consideration for the diagnostic classification of medulloblastoma. PMID- 24219921 TI - A multi-disciplinary approach to medication safety and the implication for nursing education and practice. AB - BACKGROUND: Medication management is a complex multi-stage and multi-disciplinary process, involving doctors, pharmacists, nurses and patients. Errors can occur at any stage from prescribing, dispensing and administering, to recording and reporting. There are a number of safety mechanisms built into the medication management system and it is recognised that nurses are the final stage of defence. However, medication error still remains a major challenge to patient safety globally. OBJECTIVES: This paper aims to illustrate two main aspects of medication safety practices that have been elicited from an action research study in a Scottish Health Board and three local Higher Education Institutions: firstly current medication safety practices in two clinical settings; and secondly pre and post-registration nursing education and teaching on medication safety. METHOD: This paper is based on Phase One and Two of an Action Research project. An ethnography-style observational method, influenced by an Appreciative Inquiry (AI) approach was adapted to study the everyday medication management systems and practices of two hospital wards. This was supplemented by seven in-depth interviews with nursing staff, numerous informal discussions with healthcare professionals, two focus-groups, one peer-interview and two in-depth individual interviews with final year nursing students from three Higher Education Institutions in Scotland. RESULT: This paper highlights the current positive practical efforts in medication safety practices in the chosen clinical areas. Nursing staff do employ the traditional 'five right' principles - right patient, right medication, right dose, right route and right time - for safe administration. Nursing students are taught these principles in their pre registration nursing education. However, there are some other challenges remaining: these include the establishment of a complete medication history (reconciliation) when patients come to hospital, the provision of an in-depth training in pharmacological knowledge to junior nursing staff and pre registration nursing students. CONCLUSION: This paper argues that the 'five rights' principle during medication administration is not enough for holistic medication safety and explains two reasons why there is a need for strengthened multi-disciplinary team-work to achieve greater patient safety. To accomplish this, nurses need to have sufficient knowledge of pharmacology and medication safety issues. These findings have important educational implications and point to the requirement for the incorporation of medication management and pharmacology in to the teaching curriculum for nursing students. There is also a call for continuing professional development opportunities for nurses working in clinical settings. PMID- 24219925 TI - Houses at Murnau: Wassily Kandinsky. PMID- 24219922 TI - Continuing professional development and changed re-registration requirements: midwives' reflections. AB - BACKGROUND: In 2010 new legislation in Australia led to the establishment of the Australian Health Practitioner Regulatory Authority standards, now used to manage nursing and midwifery registration and the annual re-registration requirements for midwives and nurses. These clearly articulate the continuing professional development (CPD) requirements together with a guiding framework. Individuals need to engage in adult pedagogy which makes explicit the need for self examination to identify and prioritise their learning needs. OBJECTIVES: This study aimed to investigate how existing registered midwives approach and are challenged by these changed statutory requirements in Australia, particularly completion of CPD activity. DESIGN: This paper reports the findings from phase one of a two phase, longitudinal, case study in which midwives describe their experience during in-depth qualitative interviews. SETTING: Australia PARTICIPANTS: A sample of 20 female participants was recruited nationally from four states using a purposive sampling approach to provide maximum variation to explore the issue. METHODS: Each participant took part in an in-depth interview. In order to facilitate reflection on experiences each participant was asked to discuss an object that held professional value or meaning to them. RESULTS: A key theme in the findings is the relationship between motivation which influences the decisions that midwives are making about CPD, their ongoing registration and practice context. The findings reveal implicit values and beliefs about practice relationships and how these function as motivational factors that influence midwives' decisions about CPD and practice options. CONCLUSIONS: The findings provide insight into the need for system wide dialogue to devise ways to support midwives to maintain as well as to continue to develop their practice, through CPD and to acknowledge the challenges faced by those midwives who currently hold dual registration as a registered nurse in the context of the changed requirements. PMID- 24219926 TI - Shutdown underscored vulnerability of US public health and biomedical research to political wrangling. PMID- 24219927 TI - APA targets unnecessary antipsychotic use. PMID- 24219928 TI - Greater nurse staffing may lower hospital readmissions. PMID- 24219938 TI - The toxic politics of health care. PMID- 24219939 TI - Toward a new social compact for health research. PMID- 24219940 TI - Going to the moon in health care: medicine's Big Hairy Audacious Goal (BHAG). PMID- 24219942 TI - Academic health centers and the evolution of the health care system. PMID- 24219941 TI - The disruptive innovation of price transparency in health care. PMID- 24219943 TI - Unraveling the physician supply dilemma. PMID- 24219944 TI - Resolving the tension between population health and individual health care. PMID- 24219945 TI - Reliable and sustainable comprehensive care for frail elderly people. PMID- 24219946 TI - A health care encounter of the 21st century. PMID- 24219947 TI - Consumers gaining ground in health care. PMID- 24219948 TI - The media and health care reform. PMID- 24219949 TI - A piece of my mind. Removing the "Me" from "MD". PMID- 24219950 TI - Critical issues in US health care: health care on the edge. PMID- 24219951 TI - The anatomy of health care in the United States. AB - Health care in the United States includes a vast array of complex interrelationships among those who receive, provide, and finance care. In this article, publicly available data were used to identify trends in health care, principally from 1980 to 2011, in the source and use of funds ("economic anatomy"), the people receiving and organizations providing care, and the resulting value created and health outcomes. In 2011, US health care employed 15.7% of the workforce, with expenditures of $2.7 trillion, doubling since 1980 as a percentage of US gross domestic product (GDP) to 17.9%. Yearly growth has decreased since 1970, especially since 2002, but, at 3% per year, exceeds any other industry and GDP overall. Government funding increased from 31.1% in 1980 to 42.3% in 2011. Despite the increases in resources devoted to health care, multiple health metrics, including life expectancy at birth and survival with many diseases, shows the United States trailing peer nations. The findings from this analysis contradict several common assumptions. Since 2000, (1) price (especially of hospital charges [+4.2%/y], professional services [3.6%/y], drugs and devices [+4.0%/y], and administrative costs [+5.6%/y]), not demand for services or aging of the population, produced 91% of cost increases; (2) personal out-of-pocket spending on insurance premiums and co-payments have declined from 23% to 11%; and (3) chronic illnesses account for 84% of costs overall among the entire population, not only of the elderly. Three factors have produced the most change: (1) consolidation, with fewer general hospitals and more single-specialty hospitals and physician groups, producing financial concentration in health systems, insurers, pharmacies, and benefit managers; (2) information technology, in which investment has occurred but value is elusive; and (3) the patient as consumer, whereby influence is sought outside traditional channels, using social media, informal networks, new public sources of information, and self-management software. These forces create tension among patient aims for choice, personal care, and attention; physician aims for professionalism and autonomy; and public and private payer aims for aggregate economic value across large populations. Measurements of cost and outcome (applied to groups) are supplanting individuals' preferences. Clinicians increasingly are expected to substitute social and economic goals for the needs of a single patient. These contradictory forces are difficult to reconcile, creating risk of growing instability and political tensions. A national conversation, guided by the best data and information, aimed at explicit understanding of choices, tradeoffs, and expectations, using broader definitions of health and value, is needed. PMID- 24219952 TI - Hospitals, market share, and consolidation. AB - A large reduction in use of inpatient care combined with the incentives in the Affordable Care Act is leading to significant consolidation in the hospital industry. What was once a set of independent hospitals having arms-length relationships with physicians and clinicians who provide ambulatory care is becoming a small number of locally integrated health systems, generally built around large, prestigious academic medical centers. The typical region in the United States has 3 to 5 consolidated health systems, spanning a wide range of care settings, and a smaller fringe of health care centers outside those systems. Consolidated health systems have advantages and drawbacks. The advantages include the ability to coordinate care across different practitioners and sites of care. Offsetting this is the potential for higher prices resulting from greater market power. Market power increases because it is difficult for insurers to bargain successfully with one of only a few health systems. Antitrust authorities are examining these consolidated systems as they form, but broad conclusions are difficult to draw because typically the creation of a system will generate both benefit and harm and each set of facts will be different. Moreover, the remedies traditionally used (eg, blocking the transaction or requiring that the parties divest assets) by antitrust authorities in cases of net harm are limited. For this reason, local governments may want to introduce new policies that help ensure consumers gain protection in the event of consolidation, such as insurance products that charge consumers more for high-priced clinicians and health care centers, bundling payments to clinicians and health care organizations to eliminate the incentives of big institutions to simply provide more care, and establishing area-specific price or spending targets. PMID- 24219953 TI - Increasing demands for quality measurement. AB - Measurement of health care quality and patient safety is rapidly evolving, in response to long-term needs and more recent efforts to reform the US health system around "value." Development and choice of quality measures is now guided by a national quality strategy and priorities, with a public-private partnership, the National Quality Forum, helping determine the most worthwhile measures for evaluating and rewarding quality and safety of patient care. Yet there remain a number of challenges, including diverse purposes for quality measurement, limited availability of true clinical measures leading to frequent reliance on claims data with its flaws in determining quality, fragmentation of measurement systems with redundancy and conflicting conclusions, few high-quality comprehensive measurement systems and registries, and rapid expansion of required measures with hundreds of measures straining resources. The proliferation of quality measures at the clinician, hospital, and insurer level has created challenges and logistical problems. Recommendations include raising the bar for qualtiy measurements to achieve transformational rather than incremental change in the US quality measurement system, promoting a logical set of measures for the various levels of the health system, leaving room for internal organizational improvement, harmonizing the various national and local quality measurement systems, anchoring on National Quality Forum additions and subtractions of measures to be applied, reducing reliance on and retiring claims-based measures as quickly as possible, promoting comprehensive measurement such as through registries with deep understanding of patient risk factors and outcomes, reducing attention to proprietary report cards, prompt but careful transition to measures from electronic health records, and allocation of sufficient resources to accomplish the goals of an efficient, properly focused measurement system. PMID- 24219954 TI - State repayment programs for health care education loans. PMID- 24219955 TI - Preventable acute care spending for medicare patients. PMID- 24219956 TI - Preventable acute care spending for medicare patients. PMID- 24219957 TI - New definition of term pregnancy. PMID- 24219958 TI - Preventable acute care spending for medicare patients-reply. PMID- 24219959 TI - Term pregnancy-reply. PMID- 24219963 TI - The passing of the family doctor: George W. Guthrie, M.D., Wilkes-Barre, PA. PMID- 24219964 TI - JAMA Patient Page. US Health compared with like countries. PMID- 24219965 TI - Substrate-induced effects on the optical properties of individual ZnO nanorods with different diameters. AB - We present the influence of a substrate on the properties of well-dispersed individual ZnO nanorods (NRs) with different diameters, especially on the photoluminescence (PL) properties. The studied ZnO NRs were partially supported by the quartz substrate and partially suspended in air. Continuous redshift and intensity decrease of the near band-edge emission (NBE) were observed along the suspended segment of the ZnO NRs due to the increasing temperature under UV laser excitation, suggesting that the presence of the substrate can effectively enhance the heat-sinking capability of ZnO NRs. Based on the PL measurements on individual suspended ZnO NRs with diameters from 86 nm to 2.35 MUm, the redshift of NBE along the suspended segment was more obvious for ZnO NRs with a smaller diameter, indicating that the thermal conductive ability increases as diameter increases. Additionally, by combining the experimental and simulation results, we found that the presence of the substrate also quenched the whispering gallery modes (WGMs) of the ZnO NRs with a diameter above about 350 nm due to the symmetry breaking induced by the quartz substrate which has a larger refractive index compared with air. Our studies confirm that the substrate significantly influences the properties of ZnO NRs. To fully utilize the potential properties of nanomaterials for applications in nanodevices, the substrate-induced effects should be considered thoughtfully. PMID- 24219966 TI - Osthole inhibits proliferation and induces apoptosis in human osteosarcoma cells. AB - OBJECTIVE: The purpose of this study was to investigate the effect of osthole on osteosarcoma cell proliferation and apoptosis. METHOD: Cell counting Kit-8 assay was performed to establish the effects of osthole on osteosarcoma MG-63 cell proliferation. Annexin V-FITC/PI was performed to analyze the apoptotic rate of the cells. RESULT: The inhibitory effects of osthole on the expression of BCL-2, BAX, and caspase-3 were detected by Western blotting. Osthole inhibited the growth of human osteosarcoma MG-63 cells by inhibiting cell proliferation and induced cell apoptosis. Western blotting demonstrated that osthole downregulated the expressions of BCL-2 and caspase-3 and upregulated the expression of BAX in human osteosarcoma cells. CONCLUSION: Osthole can inhibit osteosarcoma cell proliferation and induced apoptosis effectively in a dose-dependent manner through downregulating the expression of BCL-2 and caspase-3 proteins levels and upregulating the expression of BAX proteins levels. PMID- 24219967 TI - Population pharmacokinetics of adefovir dipivoxil tablets in healthy Chinese volunteers. AB - AIM: To develop a population pharmacokinetic model of adefovir dipivoxil in healthy volunteers and evaluate the effect of individual factors on the pharmacokinetics of adefovir dipivoxil. METHODS: Plasma concentration data collected from 32 healthy Chinese subjects in a Phase I clinical study was pooled. Subjects received a single oral dose of 10 mg, 20 mg, or 30 mg adefovir dipivoxil, or multiple doses of 10 mg once a day for 9 days. Plasma concentrations of adefovir dipivoxil were measured using a validated liquid chromatography-mass spectrometric method. A nonlinear mixed-effect model was used to analyze the plasma concentration data of adefovir dipivoxil in healthy volunteers and to calculate the relevant parameters as well as inter- and intra individual variability. RESULTS: The time course of adefovir dipivoxil concentration is best described by a first-order absorption and first-order elimination two-compartment model with lag time. The final estimate of total body clearance (CL) is 56.9 L/h and 78.7 L/h for single and multiple dosing regimen, respectively; the volume distribution of the central compartment (V2) is 106 L; inter-compartmental clearance (Q) is 220 L/h; volume distribution of the peripheral compartment (V3) is 498 L and 800 L for single and multiple dosing regimen, respectively; absorption rate is 0.509 h-1; and lag time is 0.315 hours. The inter-individual variabilities of CL and V2 were 22.4% and 58.9%, respectively. The proportional error of residual variability is 14.1% and the additive error is 0.30 ng/L. The final pharmacokinetic model was evaluated using a bootstrap method. CONCLUSIONS: A nonlinear mixed effect model for oral adefovir dipivoxil formulations was developed in healthy Chinese subjects. A multiple dosing regimen may significantly increase the body clearance and volume distribution of the peripheral compartment compared to a single dosing regimen. *These authors contribute equally to this work. PMID- 24219968 TI - Exosomal microRNA transfer varies with specific microRNAs functional in colorectal cancer and cellular differentiation. PMID- 24219969 TI - NSCLC cells adapted to EGFR inhibition accumulate EGFR interacting proteins and down-regulate microRNA related to epithelial-mesenchymal transition. PMID- 24219970 TI - Common genetic variants do not associate with CAD in familial hypercholesterolemia. AB - In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49 0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD. PMID- 24219971 TI - Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription. AB - BACKGROUND: Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription. FINDINGS: Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes. CONCLUSIONS: Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types. PMID- 24219973 TI - Fed-batch SSCF using steam-exploded wheat straw at high dry matter consistencies and a xylose-fermenting Saccharomyces cerevisiae strain: effect of laccase supplementation. AB - BACKGROUND: Lignocellulosic bioethanol is expected to play an important role in fossil fuel replacement in the short term. Process integration, improvements in water economy, and increased ethanol titers are key considerations for cost effective large-scale production. The use of whole steam-pretreated slurries under high dry matter (DM) conditions and conversion of all fermentable sugars offer promising alternatives to achieve these goals. RESULTS: Wheat straw slurry obtained from steam explosion showed high concentrations of degradation compounds, hindering the fermentation performance of the evolved xylose recombinant Saccharomyces cerevisiae KE6-12 strain. Fermentability tests using the liquid fraction showed a higher number of colony-forming units (CFU) and higher xylose consumption rates when treating the medium with laccase. During batch simultaneous saccharification and co-fermentation (SSCF) processes, cell growth was totally inhibited at 12% DM (w/v) in untreated slurries. However, under these conditions laccase treatment prior to addition of yeast reduced the total phenolic content of the slurry and enabled the fermentation. During this process, an ethanol concentration of 19 g/L was obtained, corresponding to an ethanol yield of 39% of the theoretical yield. By changing the operation from batch mode to fed-batch mode, the concentration of inhibitors at the start of the process was reduced and 8 g/L of ethanol were obtained in untreated slurries with a final consistency of 16% DM (w/v). When fed-batch SSCF medium was supplemented with laccase 33 hours after yeast inoculation, no effect on ethanol yield or cell viability was found compared to untreated fermentations. However, if the laccase supplementation (21 hours after yeast inoculation) took place before the first addition of substrate (at 25 hours), improved cell viability and an increased ethanol titer of up to 32 g/L (51% of the theoretical) were found. CONCLUSIONS: Laccase treatment in SSCF processes reduces the inhibitory effect that degradation compounds have on the fermenting microorganism. Furthermore, in combination with fed-batch operational mode, laccase supplementation allows the fermentation of wheat straw slurry at high DM consistencies, improving final ethanol concentrations and yields. PMID- 24219974 TI - Staging classification for cancer of the ovary, fallopian tube, and peritoneum. PMID- 24219975 TI - The influence of ionized impurity scattering on the thermopower of Si nanowires. AB - The thermopower of Si nanowires was investigated on the basis of electronic transport theory, taking into account ionized impurity scattering as well as electron-phonon scattering. It was found that the enhancement of the Seebeck coefficient in nanowires arising from quantum confinement is unimportant due to the ionized impurity scattering associated with donor deactivation. Furthermore, because the electrical conductivity is degraded significantly as the nanowire size becomes smaller, despite the accompanying slightly enhanced Seebeck coefficient, the reduction of the nanowire size is not beneficial, at least for the thermopower of devices. PMID- 24219976 TI - Intraoperative radiotherapy for breast cancer deserves a mention. PMID- 24219977 TI - Free radical routes for prebiotic formation of DNA nucleobases from formamide. AB - Modeling the complicated chemical reactions in the interstellar medium and surface materials of Titan is nontrivial. Since both the atmosphere and the surface are rich in organic molecules, the chemistry may have important implications for the origin of biomolecules. Prebiotic synthesis of DNA nucleobases from simple molecules such as formamide has been known for more than half a century. In this study, new free radical pathways leading to the synthesis of guanine, hypoxanthine, purine, and adenine have been studied using density functional theory (B3LYP with the 6-311G(d,p) basis set). The pathways of the selected nucleobases demonstrate the importance of free radicals in the production of useful biomolecules under conditions appropriate for the interstellar medium or on Titan. The pathways may be universal in nature and proceed without solvent requirements. Calculations indicate that radical pathways yield lower reaction barriers as compared to previously reported pathways. Overall, these results suggest that the chemistry on Titan's surface and/or the growth of organic particulates in the haze layers in Titan's atmosphere likely involve free radicals. The mechanisms demonstrate that important prebiotic precursors can be predicted. The reaction sequences reported here may lead to the production and build-up of molecules with prebiotic relevance. PMID- 24219978 TI - Reactivity to accelerometer measurement of children and adolescents. AB - PURPOSE: Awareness of being monitored can influence participants' habitual physical activity (PA) behavior. This reactivity effect may threaten the validity of PA assessment. Reports on reactivity when measuring the PA of children and adolescents have been inconsistent. The aim of this study was to investigate whether PA outcomes measured by accelerometer devices differ from measurement day to measurement day and whether the day of the week and the day on which measurement started influence these differences. METHODS: Accelerometer data (counts per minute [cpm]) of children and adolescents (n = 2081) pooled from eight studies in Switzerland with at least 10 h of daily valid recording were investigated for effects of measurement day, day of the week, and start day using mixed linear regression. RESULTS: The first measurement day was the most active day. Counts per minute were significantly higher than on the second to the sixth day, but not on the seventh day. Differences in the age-adjusted means between the first and consecutive days ranged from 23 to 45 cpm (3.6%-7.1%). In preschoolchildren, the differences almost reached 10%. The start day significantly influenced PA outcome measures. CONCLUSIONS: Reactivity to accelerometer measurement of PA is likely to be present to an extent of approximately 5% on the first day and may introduce a relevant bias to accelerometer-based studies. In preschoolchildren, the effects are larger than those in elementary and secondary schoolchildren. As the day of the week and the start day significantly influence PA estimates, researchers should plan for at least one familiarization day in school-age children and randomly assign start days. PMID- 24219980 TI - Adjuvant platinum-based chemotherapy for borderline serous ovarian tumors with invasive implants. AB - BACKGROUND: Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20-40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. METHODS: Retrospective study of serous BOT+invasive implants treated with adjuvant CT. RESULTS: 36 patients were referred with serous BOTs+invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N=4). The majority (72%) received a combination of platinum+taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3 months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5 year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. CONCLUSION: This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants. PMID- 24219979 TI - The ETS transcription factor Etv1 mediates FGF signaling to initiate proneural gene expression during Xenopus laevis retinal development. AB - Fibroblast growth factor signaling plays a significant role in the developing eye, regulating both patterning and neurogenesis. Members of the Pea3/Etv4 subfamily of ETS-domain transcription factors (Etv1, Etv4, and Etv5) are transcriptional activators that are downstream targets of FGF/MAPK signaling, but whether they are required for eye development is unknown. We show that in the developing Xenopus laevis retina, etv1 is transiently expressed at the onset of retinal neurogenesis. We found that etv1 is not required for eye specification, but is required for the expression of atonal-related proneural bHLH transcription factors, and is also required for retinal neuron differentiation. Using transgenic reporters we show that the distal atoh7 enhancer, which is required for the initiation of atoh7 expression in the Xenopus retina, is responsive to both FGF signaling and etv1 expression. Thus, we conclude that Etv1 acts downstream of FGF signaling to regulate the initiation of neurogenesis in the Xenopus retina. PMID- 24219981 TI - Tumor-stroma ratio is an independent predictor for survival in early cervical carcinoma. AB - OBJECTIVE: Tumor-stroma ratio (TSR) has recently been identified as an independent prognostic parameter for several solid tumors. The aim of the present study was to evaluate the prognostic role of TSR in early cervical cancer. METHODS: A cohort of 184 patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stages IA2-IIA) were enrolled in this study. TSR was estimated on hematoxylin-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients with less than 50% stroma were classified as stroma-poor and patients with >= 50% stroma were classified as stroma-rich. The relationship between TSR and survival time was statistically analyzed. RESULTS: The disease-free survival and overall survival rates were 88.44% and 92.52%, respectively, in the stroma-poor group, and 62.16% and 70.27%, respectively, in the stroma-rich group. Both the disease free and overall survival rates in the stroma-poor group were significantly better than those in the stroma-rich group (p=0.001). In a multivariate analysis, TSR was further confirmed as a significant prognostic factor for disease-free survival (hazard ratio 3.125; p=0.005) and overall survival (hazard ratio 3.464; p=0.003), independent of tumor size, FIGO stage and lymph node metastasis. CONCLUSION: Our study identified that TSR was an independent prognostic factor of early cervical cancer. Patients with stroma-rich tumors had worse prognosis and higher risk of relapse compared with those with stroma-poor tumors. Considering its simplicity and availability for conventional clinical pathology, TSR may serve as a new prognostic histological characteristic in early cervical cancer. PMID- 24219982 TI - Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors. AB - OBJECTIVE: To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel. METHODS: Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m(2)). The primary endpoint was PFS at 2 years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment. RESULTS: All patients completed VCB and 19/23 (83%) completed both VCB and 3 cycles of chemotherapy. Mean time to complete VCB was 14.5 days with minimal acute toxicity noted. At 6 months, all toxicity related to VCB had resolved. In total 60 cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5 months, 91% of patients remained progression free at 2 years. Four patients experienced a recurrence; they recurred both locally and distant. CONCLUSIONS: Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population. PMID- 24219983 TI - Population-based treatment and outcomes of Stage I uterine serous carcinoma. AB - OBJECTIVE: Uterine serous carcinoma (USC) is a rare type of endometrial cancer that often recurs in patients with Stage I disease. Our objective was to evaluate treatment and outcomes in Stage I USC in the context of a population-based study. METHODS: This was a population-based retrospective cohort study of all patients with Stage I USC in British Columbia, Canada from 2004 to 2012. The British Columbia Cancer Agency (BCCA) recommends three cycles of paclitaxel and carboplatin chemotherapy followed by pelvic radiotherapy for all women with Stage I USC and any myometrial invasion (Stage IA MI-). If no myometrial invasion (Stage IA MI-), no postoperative treatment is given. Patient and disease characteristics, surgery, adjuvant therapy, recurrence rates and sites, and 5 year disease-free survival rates were evaluated. RESULTS: Of the 127 patients with Stage I USC, 41 were Stage IA MI-, 56 Stage IA MI+, and 30 Stage IB. Median follow-up was 25 months (2-98 months). Five year disease-free survival rates were 80.7%, 74.4%, and 48.5% for Stages IA MI-, IA MI+, and IB, respectively, and recurrence rates according to BCCA guidelines were 10%, 2.9% and 30%, respectively. Of the 18 with recurrences, 13 had a distant component (72.2%). There were no pelvic recurrences among those receiving adjuvant radiotherapy. CONCLUSION: Our current protocol of observation alone postoperatively for Stage IA MI- and chemoradiotherapy for Stage IA MI+ is associated with a low recurrence rate. In contrast, those with Stage IB USC have a higher recurrence rate despite chemoradiotherapy, and likely require alternate treatment strategies. PMID- 24219984 TI - How distressing is referral to colposcopy in cervical cancer screening?: a prospective quality of life study. AB - OBJECTIVE: Referral for colposcopy because of abnormal Pap test results is likely to be distressing, but the extent and duration of these effects are unknown. We aimed to fill this gap. METHODS: We conducted a prospective observational study at two departments of Obstetrics and Gynecology (an academic and a non-academic setting). Women referred for colposcopy completed questionnaires before colposcopy, and at 1, 3, and 6 months afterwards. A reference group of 706 screen participants, aged 29-60 years old, was included and completed questionnaires once. Main outcome measures were generic health-related quality of life (HRQoL), assessed through the EQ-5D and the SF-12 physical and mental scores (PCS-12 and MCS-12); anxiety as assessed by STAI-6, and screen-specific anxiety as assessed by the psychological consequences questionnaire (PCQ). RESULTS: 154 women responded to the questionnaire, of whom 132 were included in the analyses. Histological results were CIN 1 in 17/115 women (15%) and CIN 2+ in 62 (54%). In 36 women (31%) there was no histologically confirmed neoplasia. Before colposcopy physical HRQoL scores were similar or slightly better than in the reference group, while mental HRQoL (MSC-12) and (screen-specific) anxiety were worse (p<0.001). Irrespective of CIN-grades, anxiety washed out during follow-up (p<0.001), with changes being clinically relevant. CONCLUSIONS: Referral for gynecological evaluation because of abnormal PAP-test results was distressing. Anxiety--and not the physical burden of management--seemed to be the most bothersome to women. For all CIN-grades, distress disappeared over six months following colposcopy, suggesting a reassuring effect of gynecological management. PMID- 24219985 TI - Mental health pre-registration nursing students' experiences of group clinical supervision: a UK longitudinal qualitative study. AB - There is widespread international interest in the use of clinical supervision in nursing as well as recognition of the need to introduce nursing students to its concepts and value. This article reports on a three-year longitudinal qualitative focus group study which explored students' views and experiences of a group clinical supervision initiative. Students attended supervision groups facilitated by teaching staff over their three year pre-registration mental health nursing course, with a main aim of developing skills, knowledge and attitudes as supervisees. The findings showed that students derived benefit from the experience, gained greater awareness of the nature of supervision and became active supervisees within their groups. These benefits took time to emerge and were not universal however. While the findings support the value of exposing students to the experience of group clinical supervision educators wishing to implement such a programme need to address a host of issues. These include; the preparation of students, structural and resource concerns, and issues relating to group dynamics. PMID- 24219986 TI - Physical activity helps patients with cancer too. PMID- 24219987 TI - Radiosensitization of noradrenaline transporter-expressing tumour cells by proteasome inhibitors and the role of reactive oxygen species. AB - BACKGROUND: The radiopharmaceutical 131I-metaiodobenzylguanidine (131I-MIBG) is used for the targeted radiotherapy of noradrenaline transporter (NAT)-expressing neuroblastoma. Enhancement of 131I-MIBG's efficacy is achieved by combination with the topoisomerase I inhibitor topotecan - currently being evaluated clinically. Proteasome activity affords resistance of tumour cells to radiation and topoisomerase inhibitors. Therefore, the proteasome inhibitor bortezomib was evaluated with respect to its cytotoxic potency as a single agent and in combination with 131I-MIBG and topotecan. Since elevated levels of reactive oxygen species (ROS) are induced by bortezomib, the role of ROS in tumour cell kill was determined following treatment with bortezomib or the alternative proteasome inhibitor, MG132. METHODS: Clonogenic assay and growth of tumour xenografts were used to investigate the effects of proteasome inhibitors alone or in combination with radiation treatment. Synergistic interactions in vitro were evaluated by combination index analysis. The dependency of proteasome inhibitor induced clonogenic kill on ROS generation was assessed using antioxidants. RESULTS: Bortezomib, in the dose range 1 to 30 nM, decreased clonogenic survival of both SK-N-BE(2c) and UVW/NAT cells, and this was prevented by antioxidants. It also acted as a sensitizer in vitro when administered with X-radiation, with 131I MIBG, or with 131I-MIBG and topotecan. Moreover, bortezomib enhanced the delay of the growth of human tumour xenografts in athymic mice when administered in combination with 131I-MIBG and topotecan. MG132 and bortezomib had similar radiosensitizing potency, but only bortezomib-induced cytotoxicity was ROS dependent. CONCLUSIONS: Proteasome inhibition shows promise for the treatment of neuroblastoma in combination with 131I-MIBG and topotecan. Since the cytotoxicity of MG132, unlike that of bortezomib, was not ROS-dependent, the latter proteasome inhibitor may have a favourable toxicity profile in normal tissues. PMID- 24219988 TI - Amphisomes: out of the autophagosome shadow? AB - Amphisomes are intermediate organelles, formed during autophagy through the fusion between autophagosomes and endosomes. Complex multivesicular vacuoles that resemble amphisomes have been observed in various cell types, but whether they have cellular roles other than being a precursor structure is still enigmatic. While autophagy-related (ATG) proteins interact with the endocytic pathways in other processes different from autophagy, Patel and colleagues now report that these factors come together to generate amphisome-like compartments that regulate mucin secretion in goblet cells. PMID- 24219989 TI - Acetylation of p53 stimulates miRNA processing and determines cell survival following genotoxic stress. AB - It is widely accepted that different forms of stress activate a common target, p53, yet different outcomes are triggered in a stress-specific manner. For example, activation of p53 by genotoxic agents, such as camptothecin (CPT), triggers apoptosis, while non-genotoxic activation of p53 by Nutlin-3 (Nut3) leads to cell-cycle arrest without significant apoptosis. Such stimulus-specific responses are attributed to differential transcriptional activation of various promoters by p53. In this study, we demonstrate that CPT, but not Nut3, induces miR-203, which downregulates anti-apoptotic bcl-w and promotes cell death in a p53-dependent manner. We find that acetylation of K120 in the DNA-binding domain of p53 augments its association with the Drosha microprocessor and promotes nuclear primary miRNA processing. Knockdown of human orthologue of Males absent On the First (hMOF), the acetyltransferase that targets K120 in p53, abolishes induction of miR-203 and cell death mediated by CPT. Thus, this study reveals that p53 acetylation at K120 plays a critical role in the regulation of the Drosha microprocessor and that post-transcriptional regulation of gene expression by p53 via miRNAs plays a role in determining stress-specific cellular outcomes. PMID- 24219990 TI - Feeling both victim and perpetrator: investigating duality within the needs-based model. AB - Victimized versus perpetrating individuals or groups are known to experience enhanced needs for empowerment or acceptance, respectively. The present research examined the emotional needs and consequent anti- and prosocial behaviors (e.g., vengefulness vs. helpfulness) of individuals or groups serving both as victims and perpetrators simultaneously ("duals"). Focusing on interpersonal transgressions, Study 1 used variations of the dictator game to induce participants with victimization, perpetration, duality, or none (control). Duals showed heightened needs for both empowerment and acceptance and equal willingness to reconcile following either empowering or accepting messages from their adversaries. However, duals' need for empowerment overrode their need for acceptance in determining behavior. Similar to victims, and unlike perpetrators, duals showed greater antisocial (rather than prosocial) behavior. Study 2 replicated this pattern on the intergroup level, inducing Israeli Jews with victimization, perpetration, or duality using a recall task referring to the Israeli-Palestinian conflict. Theoretical and practical implications are discussed. PMID- 24219991 TI - Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs. AB - A series of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 were designed as new heterocyclic analogs of combretastatin A-4 (CA-4). Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)-thiazole thione. The general synthetic strategy to prepare compounds 5 was based on the cyclocondensation reaction between triethylammonium N-(trimethoxyphenyl)dithiocarbamate and appropriate phenacyl halide. The cytotoxic activity evaluation of 3 (trimethoxyphenyl)-2(3H)-thiazole thiones 5 against human cancer cell lines T47D, MCF-7 and MDA-MB-231 demonstrated that 4-methyl analog 5f showed the highest activity against all cell lines. Compound 5f had no significant toxicity towards non-tumoral cells MRC-5 and its cytotoxicity was apparently selective for cancer cells. The results of bioassays showed that the representative compound 5f depolymerized tubulin, inhibited cell proliferation, and induced apoptosis in cancer cells. PMID- 24219992 TI - The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker. AB - The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2 azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2 hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50 = 17 MUM) and feline herpes virus (EC50 = 24 MUM) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC50 in the 2.8-12 MUM range. PMID- 24219994 TI - Universal behavior of magnetoresistance in quantum dot arrays with different degrees of disorder. AB - The magnetoresistance in a two-dimensional array of Ge/Si quantum dots was studied in a wide range of zero magnetic field conductances, where the transport regime changes from a hopping to a diffusive one. The behavior of the magnetoresistance is found to be similar for all samples--it is negative in weak fields and becomes positive with increasing magnetic field. The result apparently contradicts existing theories. To explain experimental data we suggest that clusters of overlapping quantum dots are formed. These clusters are assumed to have metal-like conductance, the charge transfer taking place via hopping between the clusters. Relatively strong magnetic field shrinks electron wavefunctions, decreasing inter-cluster hopping and, therefore, leading to a positive magnetoresistance. Weak magnetic field acts on 'metallic' clusters, destroying the interference of the electron wavefunctions corresponding to different paths (weak localization) inside clusters. The interference may be restricted either by inelastic processes, or by the cluster size. Taking into account weak localization inside clusters and hopping between them within the effective medium approximation, we extract effective parameters characterizing charge (magneto-) transport. PMID- 24219996 TI - Co-expression network analysis and genetic algorithms for gene prioritization in preeclampsia. AB - BACKGROUND: In this study, we explored the gene prioritization in preeclampsia, combining co-expression network analysis and genetic algorithms optimization approaches. We analysed five public projects obtaining 1,146 significant genes after cross-platform and processing of 81 and 149 microarrays in preeclamptic and normal conditions, respectively. METHODS: After co-expression network construction, modular and node analysis were performed using several approaches. Moreover, genetic algorithms were also applied in combination with the nearest neighbour and discriminant analysis classification methods. RESULTS: Significant differences were found in the genes connectivity distribution, both in normal and preeclampsia conditions pointing to the need and importance of examining connectivity alongside expression for prioritization. We discuss the global as well as intra-modular connectivity for hubs detection and also the utility of genetic algorithms in combination with the network information. FLT1, LEP, INHA and ENG genes were identified according to the literature, however, we also found other genes as FLNB, INHBA, NDRG1 and LYN highly significant but underexplored during normal pregnancy or preeclampsia. CONCLUSIONS: Weighted genes co expression network analysis reveals a similar distribution along the modules detected both in normal and preeclampsia conditions. However, major differences were obtained by analysing the nodes connectivity. All models obtained by genetic algorithm procedures were consistent with a correct classification, higher than 90%, restricting to 30 variables in both classification methods applied.Combining the two methods we identified well known genes related to preeclampsia, but also lead us to propose new candidates poorly explored or completely unknown in the pathogenesis of preeclampsia, which may have to be validated experimentally. PMID- 24219995 TI - Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. AB - BACKGROUND: HIV and SIV generally require CD4 binding prior to coreceptor engagement, but Env can acquire the ability to use CCR5 independently of CD4 under various circumstances. The ability to use CCR5 coupled with low-to-absent CD4 levels is associated with enhanced macrophage infection and increased neutralization sensitivity, but the additional features of these Envs that may affect cell targeting is not known. RESULTS: Here we report that CD4-independent SIV variants that emerged in vivo in a CD4+ T cell-depleted rhesus macaque model display markedly decreased plasticity of co-receptor use. While CD4-dependent Envs can use low levels of macaque CCR5 for efficient entry, CD4-independent variants required high levels of CCR5 even in the presence of CD4. CD4 independent Envs were also more sensitive to the CCR5 antagonist Maraviroc. CD4 dependent variants mediated efficient entry using human CCR5, whereas CD4 independent variants had impaired use of human CCR5. Similarly, CD4-independent Envs used the alternative coreceptors GPR15 and CXCR6 less efficiently than CD4 dependent variants. Env amino acids D470N and E84K that confer the CD4 independent phenotype also regulated entry through low CCR5 levels and GPR15, indicating a common structural basis. Treatment of CD4-dependent Envs with soluble CD4 enhanced entry through CCR5 but reduced entry through GPR15, suggesting that induction of CD4-induced conformational changes by non-cell surface-associated CD4 impairs use of this alternative co-receptor. CONCLUSIONS: CD4 independence is associated with more restricted coreceptor interactions. While the ability to enter target cells through CCR5 independently of CD4 may enable infection of CD4 low-to-negative cells such as macrophages, this phenotype may conversely reduce the potential range of targets such as cells expressing low levels of CCR5, conformational variants of CCR5, or possibly even alternative coreceptors. PMID- 24219997 TI - Size effect of lithium peroxide on charging performance of Li-O2 batteries. AB - We report herein that the particle size of Li2O2, which is the discharged product of a Li-O2 battery, remarkably influences the charging performance. As the particle size decreases, the average voltage of charge plateaus is lowered due to reduced electrode polarization and enhanced kinetics of the oxidation reaction of Li2O2. PMID- 24219998 TI - Function-related morphological characteristics and specialized structures of the avian tongue. AB - As a reflection of different life styles and environment, the tongue of vertebrates, which plays a major role in the intake and swallowing of food, displays significant morphological differences. The gross form and microscopic structure of the avian tongue differ greatly according to lifestyle. The avian tongue plays a fundamental role in many functions such as capturing, filtering, sucking and manipulating food in order to compensate absence of subsidiary organs like teeth in the oropharyngeal cavity. Variations in lingual papillae play an important role in feeding of birds, as they represent a structure similar to teeth in the upper and lower beaks and can be used to hold and direct food in the oropharyngeal cavity. Tongues of birds exhibit common as well as varying anatomical characteristics in terms of surface morphology, structure and topographical distribution of lingual papillae as well as distinct specialized structures, epithelial layers, taste buds and lingual glands. This review evaluates the important morphological peculiarities of the tongue in birds, focusing on the relationship between anatomical features and feeding functions. PMID- 24219999 TI - Students as teachers in an anatomy dissection course. AB - One way to improve students' learning outcomes and well-being is to change teaching practices to allow students to become more active participants. We used an anatomy dissection course to test a cooperative group work method in which first-year veterinary students took turns leading their peer group and were each responsible for teaching the anatomy of a particular topographic region. The important blood vessels, lymphatic system, and nerves of each region of the body were covered. Students felt that exploration of the entire topographic region helped them to acquire a comprehensive understanding of the respiratory apparatus and the cardiovascular and nervous systems. Assigning individual tasks to each group member resulted in sharing the workload equally. Open-ended comments revealed that support from other group members was important for the students' learning experience, but the results also offered insight into a lack of constructive criticism. While teaching was considered challenging, and even a stress factor that hindered learning for some students, group work was generally held to be supportive of learning. The results suggest that more thorough instruction of students in their group work and in their individual tasks is required. Some students experienced difficulty in expressing their concerns openly and in seeking guidance from teachers, demonstrating the need for further investigation regarding students' self-regulation skills. Comments from the open ended responses suggest that use of a cooperative learning method in anatomy dissection courses not only deepens student understanding of a subject but also offers first-year students an opportunity to practice the generic skills that will be needed in their future profession. PMID- 24220000 TI - Uncertainty in end-of-life care. AB - PURPOSE OF REVIEW: Uncertainty surrounding medical decision-making is particularly important during end-of-life decision-making. Doubts about the patient's best interests and prognostic accuracy may lead to conflict. RECENT FINDINGS: Many authors have suggested recently that medical attitudes to uncertainty need review. It is inappropriate to avoid discussion of uncertainty during end-of-life care and American literature suggests that patients and families accept uncertainty in end-of-life discussions. Recently, authors have advocated the concept of 'Practical Certainty' accepting that absolute certainty is rarely possible in end-of-life decision-making and openly acknowledging that the physicians are as certain as they can be in the circumstances. Allowing time to provide acceptance of a palliative care pathway and using the collective wisdom of colleagues improves the accuracy of prediction and reduces conflict at the end of life. SUMMARY: The implications of this review are that doctors should not avoid discussing uncertainty in end-of-life conversations and the article provides some recommendations for minimizing conflict arising from end-of-life discussion. PMID- 24220002 TI - Significant variation of surface spin polarization through group IV atom (C, Si, Ge, Sn) adsorption on Fe3O4(100). AB - The adsorption of group IV atoms (C, Si, Ge, Sn) on the magnetite Fe3O4(100) surface is investigated by density functional theory calculations. All these atoms prefer to bond to the surface oxygen atom which has no tetrahedral Fe(A) neighbor. The spin-up surface states of clean Fe3O4(100) are completely removed and half-metallicity is recovered by C adsorption. The spin-up band gap of the C adsorbed Fe3O4(100) surface is wider than that of the H-adsorbed one and closer to the value of bulk Fe3O4. For the adsorption of other group IV atoms, the adsorbate-substrate interaction decreases and the adsorbate-adsorbate interaction increases with the increase of atomic number Z. As a consequence, the spin polarization varies from -99.4% (C adsorption) to +44.2% (Sn adsorption) for the electronic states of the adsorbed atom integrated from -0.5 eV to the Fermi level. The ability to tune the surface spin polarization by the choice of adsorbate is of significance for magnetite-based spintronic devices. PMID- 24220001 TI - Application of TREECS Modeling System to Strontium-90 for Borschi Watershed near Chernobyl, Ukraine. AB - The Training Range Environmental Evaluation and Characterization System (TREECSTM) (http://el.erdc.usace.army.mil/treecs/) is being developed by the U.S. Army Engineer Research and Development Center (ERDC) for the U.S. Army to forecast the fate of munitions constituents (MC) (such as high explosives (HE) and metals) found on firing/training ranges, as well as those subsequently transported to surface water and groundwater. The overall purpose of TREECSTM is to provide environmental specialists with tools to assess the potential for MC migration into surface water and groundwater systems and to assess range management strategies to ensure protection of human health and the environment. The multimedia fate/transport models within TREECSTM are mathematical models of reduced form (e.g., reduced dimensionality) that allow rapid application with less input data requirements compared with more complicated models. Although TREECSTM was developed for the fate of MC from military ranges, it has general applicability to many other situations requiring prediction of contaminant (including radionuclide) fate in multi-media environmental systems. TREECSTM was applied to the Borschi watershed near the Chernobyl Nuclear Power Plant, Ukraine. At this site, TREECSTM demonstrated its use as a modeling tool to predict the fate of strontium 90 ((90)Sr). The most sensitive and uncertain input for this application was the soil-water partitioning distribution coefficient (Kd) for (90)Sr. The TREECSTM soil model provided reasonable estimates of the surface water export flux of (90)Sr from the Borschi watershed when using a Kd for (90)Sr of 200 L/kg. The computed export for the year 2000 was 0.18% of the watershed inventory of (90)Sr compared to the estimated export flux of 0.14% based on field data collected during 1999-2001. The model indicated that assumptions regarding the form of the inventory, whether dissolved or in solid phase form, did not appreciably affect export rates. Also, the percentage of non-exchangeable adsorbed (90)Sr, which is uncertain and affects the amount of (90)Sr available for export, was fixed at 20% based on field data measurements. A Monte Carlo uncertainty analysis was conducted treating Kd as an uncertain input variable with a range of 100-300 L/kg. This analysis resulted in a range of 0.13-0.27% of inventory exported to surface water compared to 0.14% based on measured field data. Based on this model application, it was concluded that the export of (90)Sr from the Borschi watershed to surface water is predominantly a result of soil pore water containing dissolved (90)Sr being diverted to surface waters that eventually flow out of the watershed. The percentage of non-exchangeable adsorbed (90)Sr and the soil-water Kd are the two most sensitive and uncertain factors affecting the amount of export. The 200-year projections of the model showed an exponential decline in (90)Sr export fluxes from the watershed that should drop by a factor of 10 by the year 2100. This presentation will focus on TREECS capabilities and the case study done for the Borschi Watershed. PMID- 24220003 TI - Application of monoclonal antibody against granulocytes of scallop Chlamys farreri on granulocytes occurrence at different developmental stages and antigenic cross-reactivity of granulocytes in five other bivalve species. AB - A monoclonal antibody (MAb) 6H7 raised specifically against granulocytes of scallop (Chlamys farreri) was employed to observe granulocyte occurrence successively in blastulae, gastrulae, trochophore larvae, D-shape larvae, umbo veliger larvae and creeping larvae of C. farreri by immunohistochemistry assay contrasted with H&E stain using semi-thin sections. Moreover, the reactivity of the MAb with granulocytes of C. farreri, Bay scallop Argopecten irradians, Japanese scallop Patinopecten yessoensis, Blue mussel Mytilus edulis, Pacific oyster Crassostrea gigas and Manila clam Ruditapes philippinarum, was detected by immunofluorescence assay (IFA) with differential interference contrast and fluorescent microscopy and flow cytometric immunofluorescence assay (FCIFA). The results showed that positive signals were first observed at D-shape larval stage, about 28 h post fertilization, after that, umbo-veliger larvae exhibited the positive cells with a diameter of 3-5 MUm distributed in velum, digestive gland and esophagus. Then in creeping larvae, the number of positive cells increased with average diameter of 5-7 MUm, and widely distributed in foot, digestive gland, gills and adductor muscles. No positive signal was found in blastulae, gastrulae and trochophore larvae. The results of IFA and FCIFA showed MAb 6H7 reacted to granulocytes of C. farreri, A. irradians, P. yessoensis and C. gigas, and the positive percentage reactivity were 53 +/- 2.5%, 15 +/- 2.5%, 12 +/- 2.1% and 19 +/- 2.1%, respectively, however, no cross-reaction was detected in hemocytes of R. philippinarum and M. edulis. PMID- 24220004 TI - Identification of a novel N4BP1-like gene from grass carp (Ctenopharyngodon idella) in response to GCRV infection. AB - Nedd4 binding protein 1 (N4BP1) has been identified as an interacting protein and a substrate of Nedd4 E3 ligase. However, the report about N4BP1's function is limit. In this study, a novel N4BP1 gene (CiN4BP1) was cloned from grass carp (Ctenopharyngodon idella). The full-length cDNA sequence of CiN4BP1 (3022 bp) included an open reading frame (ORF) of 2565 bp, which encoded a putative peptides of 854 amino acids containing one KH domain and one NYN domain. It was close homology (47% identify) to Oryzias latipes N4BP1. And mRNA expression of CiN4BP1 gene showed relatively high level in skin, gill, head kidney and spleen. After grass carp reovirus (GCRV) infection, CiN4BP1 was up-regulated in vivo and in vitro. Furthermore, overexpression of CiN4BP1 in CIK cells inhibited viral gene transcription. These data indicated that CiN4BP1 might play an important role in immune response to viral invasion. PMID- 24220005 TI - Measuring surgical outcomes in subaxial degenerative cervical spine disease patients: minimum clinically important difference as a tool for determining meaningful clinical improvement. AB - BACKGROUND: Although the concept of minimum clinically important difference (MCID) as a measurement of surgical outcome has been extensively studied, there is lack of consensus on the most valid or clinically relevant MCID calculation approach. OBJECTIVE: To compare the range of MCID threshold values obtained by different anchor-based and distribution-based approaches to determine the best clinically meaningful and statistically significant MCID for our studied group. METHODS: Eighty-eight consecutive patients undergoing surgery for subaxial degenerative cervical spine disease were analyzed from a prospective blinded database. Preoperative, 3-, and 6-month postoperative patient reported outcome (PRO) scores and blinded surgeon ratings were collected. Four calculation methods were used to calculate MCID threshold values: average change, change difference, minimum detectable change, and receiver operating characteristic (ROC) curve. Three anchors were used to evaluate meaningful improvement postsurgery: health transition item, patient overall status, and surgeon ratings. RESULTS: On average, all patients had a statistically significant improvement (P < .001) postoperatively for neck disability index (score 27.42 preoperatively to 19.42 postoperatively), physical component of the Short Form of the Medical Outcomes Study (SF-36) (33.02-42.23), mental component of the SF-36 (44-50.74), and visual analog scale (2.85-1.93). The 4 MCID approaches yielded a range of values for each PRO: 2.23 to 16.59 for physical component of the SF-36, 0.11 to 16.27 for mental component of the SF-36, and 2.72 to 12.08 for neck disability index. In comparison with health transition item and patient overall status anchors, the area under the ROC curve was consistently greater for surgeon ratings for all 4 PROs. CONCLUSION: Minimum detectable change together with surgeon ratings anchor appears to be the most appropriate MCID method. Based on our findings, this combination offers the greatest area under the ROC curve (threshold above the 95% confidence interval). The choice of the anchor did not significantly affect this result. PMID- 24220006 TI - Neck tumor dissection improved with 3-dimensional ultrasound image guidance: technical case report. AB - BACKGROUND AND IMPORTANCE: Three-dimensional ultrasound navigation has been performed to assist in resection of cranial and spinal tumors, but to the best of our knowledge, no one has described the use of real-time 3-dimensional ultrasound navigation in the resection of neck tumors beyond biopsy. CLINICAL PRESENTATION: This case report describes the use of 3-dimensional ultrasonic navigation in assisting with resection of a large neck paraganglioma. The 3-dimensional ultrasonic navigation improved real-time visualization of the carotid arteries, the trachea, and other vital structures. CONCLUSION: The use of 3-dimensional ultrasound navigation should be considered in aiding resection of large neck tumors because it can allow more efficient and safer tumor resection. PMID- 24220007 TI - Comparative effectiveness of 3-dimensional vs 2-dimensional and high-definition vs standard-definition neuroendoscopy: a preclinical randomized crossover study. AB - BACKGROUND: Although the potential benefits of 3-dimensional (3-D) vs 2 dimensional (2-D) and high-definition (HD) vs standard-definition (SD) endoscopic visualization have long been recognized in other surgical fields, such endoscopes are generally considered too large and bulky for use within the brain. The recent development of 3-D and HD neuroendoscopes may therefore herald improved depth perception, better appreciation of anatomic details, and improved overall surgical performance. OBJECTIVE: To compare simultaneously the effectiveness of 3 D vs 2-D and HD vs SD neuroendoscopy. METHODS: Ten novice neuroendoscopic surgeons were recruited from a university hospital. A preclinical randomized crossover study design was adopted to compare 3-D vs 2-D and HD vs SD neuroendoscopy. The primary outcomes were time to task completion and accuracy. The secondary outcomes were perceived task workload using the NASA (National Aeronautics and Space Administration) Task Load Index and subjective impressions of the endoscopes using a 5-point Likert scale. RESULTS: Time to task completion was significantly shorter when using the 3-D vs the 2-D neuroendoscopy (P = .001), and accuracy of probe placement was significantly greater when using the HD vs the SD neuroendoscopy (P = .009). We found that 3-D endoscopy significantly improved perceived depth perception (P < .001), HD endoscopy significantly improved perceived image quality (P < .001), and both improved participants' overall impression (P < .001). CONCLUSION: Three-dimensional neuroendoscopy and HD neuroendoscopy have differing but complementary effects on surgical performance, suggesting that neither alone can completely compensate for the lack of the other. There is therefore strong preclinical evidence to justify 3-D HD neuroendoscopy. PMID- 24220008 TI - Polyarteritis nodosa complicating multiple myeloma - a case report and review of the literature. AB - INTRODUCTION: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of small to medium-sized vessels, rarely associated with hematologic neoplasms. CASE REPORT: We report a 44-year-old man with a history of monoclonal gammopathy of undetermined significance (MGUS) who presented with rapidly progressing sensorimotor peripheral neuropathy. Two weeks after onset the patient developed severe acute acral and retinal ischemia. MR-angiography and nerve biopsy revealed a systemic necrotizing vasculitis (PAN type). At this time, bone marrow biopsy identified a smoldering multiple myeloma. Immediate immunosuppressive and anti neoplastic treatment (steroids, immunoglobulins, bortezomib combined with cyclophosphamide followed by lenalidomide maintenance) resulted in a favorable clinical outcome. After 4 years, the patient is in good clinical condition with sustained partial remission from myeloma and without evidence of relapse of PAN. CONCLUSION: This is a remarkable case of a histologically confirmed peripheral neuropathy due to polyarteritis nodosa associated with progression of MGUS to multiple myeloma. Immediate diagnosis and combined immunosuppressive and anti neoplastic treatment may improve the outcome of this potentially life-threatening clinical condition. PMID- 24220009 TI - Evaluation of PhTX-74 as subtype-selective inhibitor of GluA2-containing AMPA receptors. AB - The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are glutamate-gated cation channels that mediate fast excitatory synaptic transmission in the central nervous system. AMPARs are tetramers formed by homo- or heteromeric assembly of GluA1-4 subunits to produce multiple subtypes with varying biophysical properties. Polyamine toxins such as joro spider toxins, philanthotoxins (PhTXs), and argiotoxins are use-dependent ion channel blockers of AMPARs widely employed as highly potent antagonists of GluA2-lacking receptor subtypes. In addition to this use, recent findings have indicated that a philanthotoxin analog, PhTX-74, can distinguish among GluA2-containing AMPAR subtypes in the presence of the prototypical transmembrane AMPAR regulatory protein gamma-2 (or stargazin). Thus, PhTX-74 may be of potential use in studies of the neurobiological role of GluA2-containing subtypes. We have evaluated the pharmacological profile of PhTX-74 and related polyamine toxins at homo- and heteromeric AMPARs in the presence and absence of gamma-2. Determination of IC(50) values for inhibition of glutamate-evoked currents from Xenopus oocytes expressing recombinant homo- or heteromeric combinations of GluA1, GluA2, and GluA3 in the presence of gamma-2 shows that PhTX-74 inhibits homomeric GluA1 and GluA3 receptors nonselectively, with IC(50) values in the nanomolar range (252 356 nM), and heteromeric GluA1/A2 and GluA2/A3 receptors nonselectively, with IC(50) values in the micromolar range (22 MUM). Thus, in contrast to earlier findings, we find that PhTX-74 cannot pharmacologically discriminate between GluA2-containing AMPAR subtypes. PMID- 24220010 TI - Structural and functional analysis of g protein-coupled receptor kinase inhibition by paroxetine and a rationally designed analog. AB - Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity is important for the development of even more selective and potent small molecule therapeutics and chemical genetic probes. We first sought to understand the molecular mechanisms underlying paroxetine selectivity among GRKs. We directly measured the K(D) for paroxetine and assessed its mechanism of inhibition for each of the GRK subfamilies and then determined the atomic structure of its complex with GRK1, the most weakly inhibited GRK tested. Our results suggest that the selectivity of paroxetine for GRK2 largely reflects its lower affinity for adenine nucleotides. Thus, stabilization of off-pathway conformational states unique to GRK2 will likely be key for the development of even more selective inhibitors. Next, we designed a benzolactam derivative of paroxetine that has optimized interactions with the hinge of the GRK2 kinase domain. The crystal structure of this compound in complex with GRK2 confirmed the predicted interactions. Although the benzolactam derivative did not significantly alter potency of inhibition among GRKs, it exhibited 20-fold lower inhibition of serotonin reuptake. However, there was an associated increase in the potency for inhibition of other AGC kinases, suggesting that the unconventional hydrogen bond formed by the benzodioxole ring of paroxetine is better accommodated by GRKs. PMID- 24220011 TI - Salicylate, a catalytic inhibitor of topoisomerase II, inhibits DNA cleavage and is selective for the alpha isoform. AB - Topoisomerase II (topo II) is a ubiquitous enzyme that is essential for cell survival through its role in regulating DNA topology and chromatid separation. Topo II can be poisoned by common chemotherapeutics (such as doxorubicin and etoposide), leading to the accumulation of cytotoxic enzyme-linked DNA double stranded breaks. In contrast, nonbreak-inducing topo II catalytic inhibitors have also been described and have more limited use in clinical chemotherapy. These agents, however, may alter the efficacy of regimens incorporating topo II poisons. We previously identified salicylate, the primary metabolite of aspirin, as a novel catalytic inhibitor of topo II. We have now determined the mechanism by which salicylate inhibits topo II. As catalytic inhibitors can act at a number of steps in the topo II catalytic cycle, we used multiple independent, biochemical approaches to interrogate the catalytic cycle. Furthermore, as mammalian cells express two isoforms of topo II (alpha and beta), we examined whether salicylate was isoform selective. Our results demonstrate that salicylate is unable to intercalate DNA, and does not prevent enzyme-DNA interaction, nor does it promote stabilization of topo IIalpha in closed clamps on DNA. Although salicylate decreased topo IIalpha ATPase activity in a dose-dependent noncompetitive manner, this was secondary to salicylate-mediated inhibition of DNA cleavage. Surprisingly, comparison of salicylate's effects using purified human topo IIalpha and topo IIbeta revealed that salicylate selectively inhibits the alpha isoform. These findings provide a definitive mechanism for salicylate mediated inhibition of topo IIalpha and provide support for further studies determining the basis for its isoform selectivity. PMID- 24220012 TI - Reduced expression of claudin-2 is associated with high histological grade and metastasis of feline mammary carcinomas. AB - Claudins (CLDNs) are a family of tight junction (TJ) proteins that play an important role in maintaining cell polarity, in controlling paracellular ion flux and in regulating cell proliferation and differentiation. There is a growing body of evidence that associates changes in CLDN expression with the development of human breast cancer. In the present study CLDN-2 expression was examined immunohistochemically in samples of normal feline mammary tissue (n = 5) and mammary carcinomas (n = 52), including metastatic lesions (n = 29). Seventy-seven percent of carcinomas showed reduced CLDN-2 expression compared with that observed in normal mammary gland. Reduced expression of CLDN-2 was significantly associated with a high histological grade of carcinoma (P = 0.011), with 88.6% of grade II/III carcinomas showing decreased expression. Furthermore, CLDN-2 down regulation was significantly associated with metastatic disease (P = 0.0027), with 93.1% of cases with signs of metastasis showing decreased expression of this protein. CLDN-2 may constitute a molecular marker for identification of a subgroup of feline mammary carcinomas characterized by high histological grade and the development of metastasis. PMID- 24220013 TI - Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark. AB - OBJECTIVES: Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers on occupation and cryptorchidism. METHODS: The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other occupations. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression adjusting for parental age, birth years, parity, and geographical region. RESULTS: Sons of maternal farmers were at increased risk of cryptorchidism (157 cases; HR 1.31, 95% CI 1.12-1.53) compared to boys of mothers in other occupations (15 511 cases). Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk (72 cases; HR 1.20, 95% CI 0.95-1.52). A similar association was found for paternal horticultural workers. Sons of maternal farmers or horticultural workers who likely worked in the first trimester were not at increased risk of cryptorchidism. CONCLUSIONS: This nationwide cohort study found a slightly increased risk of cryptorchidism in sons of maternal horticultural workers and farmers. However, subgroup analyses indicated similar findings for paternal horticultural workers, and no association for women likely working in the first trimester. The main findings should therefore be interpreted with caution. PMID- 24220014 TI - A systematic review of ulnar collateral ligament reconstruction techniques. AB - BACKGROUND: Ulnar collateral ligament (UCL) reconstruction of the elbow has become increasingly more frequent among elite overhead athletes. The purpose of this study was to conduct a systematic review comparing the clinical outcomes and biomechanical results of the Jobe, modified Jobe, docking, modified docking, Endobutton, and interference screw techniques for UCL reconstruction. HYPOTHESIS: The docking technique will have significantly fewer complications and improved return-to-play rate. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Using the Medline PubMed, Cochrane, and EMBASE databases, a search was performed of all published articles, including randomized controlled trials, cohort studies, and case series, examining UCL reconstructions performed using one of the above noted techniques and excluding case reports and hybrid techniques. Statistical analysis was performed using a chi(2) test of independence and 2-proportion Z test. RESULTS: A total of 21 studies, 7 biomechanical and 14 clinical, met the inclusion criteria. There were 1368 patients. The overall complication rate was 18.6% (255/1368), further subdivided into 21 for the Jobe technique (29.2%), 203 for the modified Jobe technique (19.1%), 2 for the interference screw technique (10.0%), 2 (4.3%) for the modified docking technique, and 10 for the docking technique (6.0%). The most common complication across all studies was ulnar nerve neurapraxia in 176 patients (12.9%). The overall rate of return to play was 78.9%. CONCLUSION: Ulnar collateral ligament reconstruction utilizing the docking technique results in a significantly higher rate of return to play and a lower complication rate when compared with the Jobe and modified Jobe techniques. CLINICAL RELEVANCE: A lower complication rate can lead to increased rates of return to play and better outcomes postoperatively. PMID- 24220015 TI - Clinical outcomes of revision meniscal repair: a case series. AB - BACKGROUND: Meniscal preservation results in better clinical outcomes than meniscectomy; however, no studies have evaluated the results of revision meniscal repair. HYPOTHESIS: Revision meniscal repair can achieve good clinical outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study participants were 16 patients with symptomatic meniscal retears of a total of 96 patients who underwent primary arthroscopic meniscal repair. Fifteen of these 16 patients underwent revision meniscal repair. The mean age at revision was 27 years, and the mean duration between the primary operation and revision was 27 months. Eight patients had degenerative changes of the meniscus at revision. Clinical outcomes were assessed using the Lysholm score and the Tegner sports activity score, and image assessment was performed using magnetic resonance imaging. RESULTS: Five patients had re-retears of a resutured meniscus, and the mean duration between revision and the re-retear was 25 months (range, 8-68 months). The mean follow-up of patients without re-retears was 41 months (range, 24-74 months), and the mean Lysholm score in those without re-retears significantly improved from 81.4 points (range, 73-89 points) at pre-revision to 97.4 points (range, 90-100 points) at the final survey (P = .0001). Degenerative changes of the meniscus at the revision site were observed in all 5 patients with re-retears but in only 3 of the 10 patients without re-retears. CONCLUSION: Revision meniscal repair should be considered in the setting of a retorn meniscus without degenerative changes. PMID- 24220017 TI - Management of Combined Anterior Cruciate Ligament-Posterolateral Corner Tears: A Systematic Review. AB - BACKGROUND: A consensus on the treatment of combined anterior cruciate ligament (ACL) and posterolateral corner (PLC) injuries is still lacking. PURPOSE: To review the available literature on the management of these combined lesions to investigate the influence that injuries of knee posterolateral structures play in the outcome of an ACL lesion. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A comprehensive search was performed on PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases using various combinations of the following keywords: "posterolateral corner," "plc," "posterolateral instability," "posterolateral injury," "anterior cruciate ligament," and "acl." RESULTS: A total of 6 studies involving 95 patients were included. For those with PLC lesions, 14 patients were treated nonoperatively, 9 underwent an early anatomic repair, while the remaining 72 underwent a reconstruction. In all 95 patients, an ACL reconstruction was performed. Sixty-seven of the 72 patients who underwent a PLC reconstruction were assessed for anteroposterior laxity, with a mean side-to side difference of 1.5 +/- 1.1 mm. Evaluated by the objective International Knee Documentation Committee (IKDC) Knee Form, 88% of the patients who underwent a PLC reconstruction were graded as good/excellent (A/B). The 9 patients who underwent an early surgical repair of the PLC lesion were evaluated by means of the objective IKDC score, with 3 patients (33%) graded as good/excellent (A/B), and by means of a clinical evaluation, with 5 of 9 patients (56%) graded as 1+ for varus laxity. For the 14 patients who were managed nonoperatively for PLC injuries, the only clinical score available was the subjective IKDC score, with a mean value of 80.5 (87.8 for the 6 patients with type A PLC injuries and 75.0 for type B PLC injuries). CONCLUSION: There is a paucity of literature focused on the management of combined ACL and PLC injuries. Combined ACL and PLC reconstruction seems to be the most effective approach to these combined lesions. However, future work is needed to explore the long-term outcome of the different treatment options. PMID- 24220018 TI - Osteoblasts proliferation and differentiation stimulating activities of the main components of Fructus Psoraleae corylifoliae. AB - Osteoporosis is a disease of bones that leads to an increased risk of fracture. Fructus of Psoralea corylifolia L. (scurfpea fruit) is commonly utilized for treating bone fractures and joint diseases for thousands of years in China. This study was aimed to screen active principles, which might have the potency to stimulate osteoblasts proliferation and differentiation from scurfpea fruit. A HPLC method was established to analyze the main components in scurfpea fruit. Totally 11 compounds have been identified by comparing their retention time with correspondent standard substances. The MTT and ALP methods were utilized for the assay of osteoblasts proliferation and differentiation activity. Icariin, a prenylated flavonoid glycoside was treated as the positive control. Bavachin and isobavachin significantly stimulated cell proliferation, while bakuchiol exhibited stronger effect to enhance osteoblasts differentiation. All these compounds were found with a characterized structure that in each of their molecule backbones, a prenylated side chain was attached. These results lead to a hypothesis that prenyl group might be crucial to exhibit the activity. The structure-effect relationship of these compounds with prenyl group in mouse primary calvarial osteoblasts needs to be explored in further research. PMID- 24220016 TI - Stem cell therapies for knee cartilage repair: the current status of preclinical and clinical studies. AB - BACKGROUND: Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future. PURPOSE: The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects. STUDY DESIGN: Literature review. METHODS: A PubMed search was undertaken. The key phrase "stem cells and knee" was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and "stem cells and knee" was used as the search phrase. RESULTS: Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials. CONCLUSION: The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee's cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair. PMID- 24220020 TI - Thermochromic effects in a Jahn-Teller active CuCl(4-)6 layered hybrid system. AB - The hybrid material copper (II) tetrachloro-bis(phenyl ethyl ammonium) (C6H5CH2CH2NH3)2CuCl4, or PEACuCl, has been investigated by temperature-dependent spectroscopic absorption experiments. The absorption bands observed in the near infrared region (1.3-1.9 eV) generally exhibit redshifts with increasing temperature. The temperature-induced energy shifts of the spectral components are shown to be consistently related to temperature-induced Cu-Cl bond length changes. Additionally, the thermochromic color change is caused by a charge transfer band edge redshifting (in the visible region 2.0-2.8 eV) with increasing temperature. By comparison with similar Cu-based systems, it is suggested that this shift is caused by broadening and strengthening of the band. PMID- 24220019 TI - Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism. AB - Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID- 24220021 TI - Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus. AB - BACKGROUND: An animal model for HBV that more closely approximates the disease in humans is needed. The tree shrew (Tupaia belangeri) is closely related to primates and susceptible to HBV. We previously established that neonatal tree shrews can be persistently infected with HBV in vivo, and here present a six year follow-up histopathological study of these animals. METHODS: Group A consists of six tree shrews with persistent HBV infection, group B consists of three tree shrews with suspected persistent HBV infection, while group C consists of four tree shrews free of HBV infection. Serum and liver tissues samples were collected periodically from all animals. HBV antigen and HBV antibodies were detected by ELISA and/or TRFIA. HBV DNA in serum and in liver biopsies was measured by FQ PCR. Liver biopsies were applied for general histopathologic observation and scoring, immunohistochemical detections of HBsAg and HBcAg, and ultrastructural observation with electron microscope technique. RESULTS: Hydropic, fatty and eosinophilic degeneration of hepatocytes, lymphocytic infiltration and hyperplasia of small bile ducts in the portal area were observed in group A. One animal infected with HBV for over six years showed multiple necrotic areas which had fused to form bridging necrosis and fibrosis, and megalocytosis. The hepatic histopathological scores of group A were higher than those of group B and C. The histopathological score correlated positively with the duration of infection. CONCLUSIONS: Hepatic histopathological changes observed in chronically HBV infected tree shrews are similar to those observed in HBV-infected humans. The tree shrew may represent a novel animal model for HBV infection. PMID- 24220022 TI - Comprehensive probabilistic modelling of environmental emissions of engineered nanomaterials. AB - Concerns about the environmental risks of engineered nanomaterials (ENM) are growing, however, currently very little is known about their concentrations in the environment. Here, we calculate the concentrations of five ENM (nano-TiO2, nano-ZnO, nano-Ag, CNT and fullerenes) in environmental and technical compartments using probabilistic material-flow modelling. We apply the newest data on ENM production volumes, their allocation to and subsequent release from different product categories, and their flows into and within those compartments. Further, we compare newly predicted ENM concentrations to estimates from 2009 and to corresponding measured concentrations of their conventional materials, e.g. TiO2, Zn and Ag. We show that the production volume and the compounds' inertness are crucial factors determining final concentrations. ENM production estimates are generally higher than a few years ago. In most cases, the environmental concentrations of corresponding conventional materials are between one and seven orders of magnitude higher than those for ENM. PMID- 24220023 TI - Ingestion and transfer of microplastics in the planktonic food web. AB - Experiments were carried out with different Baltic Sea zooplankton taxa to scan their potential to ingest plastics. Mysid shrimps, copepods, cladocerans, rotifers, polychaete larvae and ciliates were exposed to 10 MUm fluorescent polystyrene microspheres. These experiments showed ingestion of microspheres in all taxa studied. The highest percentage of individuals with ingested spheres was found in pelagic polychaete larvae, Marenzelleria spp. Experiments with the copepod Eurytemora affinis and the mysid shrimp Neomysis integer showed egestion of microspheres within 12 h. Food web transfer experiments were done by offering zooplankton labelled with ingested microspheres to mysid shrimps. Microscopy observations of mysid intestine showed the presence of zooplankton prey and microspheres after 3 h incubation. This study shows for the first time the potential of plastic microparticle transfer via planktonic organisms from one trophic level (mesozooplankton) to a higher level (macrozooplankton). The impacts of plastic transfer and possible accumulation in the food web need further investigations. PMID- 24220024 TI - Systemic vascular phenotypes of Loeys-Dietz syndrome in a child carrying a de novo R381P mutation in TGFBR2: a case report. AB - BACKGROUND: Loeys-Dietz syndrome, also known as Marfan syndrome type II, is a rare connective tissue disorder caused by dominant mutations in transforming growth factor-beta receptors (TGFBR1 and 2). CASE PRESENTATION: We report a 7 year-old Japanese boy with Loeys-Dietz syndrome who carried a novel, de novo missense mutation in TGFBR2 (c.1142g > c, R381P). He showed dysmorphic faces and skeletal malformations that were typical in previous cases with Loeys-Dietz syndrome. The cardiac studies disclosed the presence of markedly dilated aortic root and patent ductus aorteriosus. The cranial magnetic resonance imaging (MRI) and angiography (MRA) detected the tortuous appearances of the bilateral middle cerebral and carotid arteries. CONCLUSION: This study depicts the systemic vascular phenotypes of a child with Loeys-Dietz syndrome that were caused by a novel heterozygous mutation of TGFR2. A large cohort with serial imaging studies for vascular phenotypes will be useful for delineating the genotype-phenotype correlations of Loeys-Dietz syndrome. PMID- 24220025 TI - Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET. AB - The radiotracer [(11)C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [(11)C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [(11)C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [(11)C]PHNO and [(11)C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [(11)C]PHNO or [(11)C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7 +/- 8%), the nucleus accumbens (10 +/- 7%), and in the globus pallidus (13 +/- 15%) measured with [(11)C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [(11)C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [(11)C]PHNO compared with [(11)C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [(11)C]PHNO is more sensitive than [(11)C]raclopride to nicotine- and amphetamine-induced DA release. [(11)C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers. PMID- 24220027 TI - Structure stability and high-temperature distortion resistance of trilayer complexes formed from graphenes and boron nitride nanosheets. AB - The molecular dynamics was employed to study the structure stability and high temperature distortion resistance of a trilayer complex formed by a monolayer graphene sandwiched in bilayer boron nitride nanosheets (BN-G-BN) and graphenes (G-G-G). The investigation shows that the optimal interlayer distances are about 0.347 nm for BN-G-BN and 0.341 nm for G-G-G. Analysis and comparison of the binding energy, van der Waals interactions between layers and radial distribution function (RDF) revealed that the BN-G-BN achieves a more stable combined structure than G-G-G. The interlayer graphene in the trilayer complex nanosheets, especially the graphene in BN-G-BN, is more integrated than monolayer graphenes in a crystal structure. The structures at high temperature of 1500 K show that the BN-G-BN exhibits less distortion than G-G-G; especially, fixing the atomic positions on up-down layers can obviously further reduce structural deformation of interlayer graphene. The result further indicates that the high-temperature distortion resistance of interlayer graphene in the trilayer complex is related to both material type and conditions of constraints at the up-down layers. PMID- 24220026 TI - Association of depressive symptoms with hippocampal volume in 1936 adults. AB - Hippocampal atrophy is reported in major depressive disorder (MDD). However, sample sizes were generally modest, and participant characteristics, including age, differed between studies. This study used a community sample to examine relationships between current depressive symptom severity and hippocampal volume across the adult lifespan. A total of 1936 adults with magnetic resonance images of the brain and Quick Inventory of Depressive Symptomatology Self-Report (QIDS SR) scores were included. Brain volumes were quantified using the FSL program. Multiple linear regressions were performed using left, right, and total hippocampal volume as criterion variables, and predictor variables of QIDS-SR total, total brain volume, age, gender, education, psychotropic medications, alcohol use, and race/ethnicity. Post hoc analyses were conducted in participants with QIDS-SR scores ?11 (moderate or greater depressive symptom severity) and <11, and older and younger adults. In the primary analysis (sample as a whole) QIDS-SR was inversely associated with total hippocampal volume (b=-0.044, p=0.032, (CI-0.019 to -0.001)) but not with left or right hippocampal volume evaluated individually. In participants with QIDS-SR scores of <11, hippocampal volumes were not associated with QIDS-SR scores. In those with QIDS-SR scores ?11 total, right, and left hippocampal volumes were modestly, but significantly, associated with QIDS-SR scores. The association between QIDS-SR scores and the hippocampal volume was much stronger in older persons. Findings suggest smaller hippocampal volumes among those with greater reported depressive symptom severity an association that is strongest in people with at least moderate depressive symptom levels. PMID- 24220028 TI - The p38-interacting protein (p38IP) regulates G2/M progression by promoting alpha tubulin acetylation via inhibiting ubiquitination-induced degradation of the acetyltransferase GCN5. AB - p38-interacting protein (p38IP) is a component of the GCN5 histone acetyltransferase-containing coactivator complex (GCN5-SAGA complex). It remains unclear whether p38IP or GCN5-SAGA is involved in cell cycle regulation. Using RNA interference to knock down p38IP, we observed that cells were arrested at the G2/M phase, exhibiting accumulation of cyclins, shrunken spindles, and hypoacetylation of alpha-tubulin. Further analysis revealed that knockdown of p38IP led to proteasome-dependent degradation of GCN5. GCN5 associated with and acetylated alpha-tubulin, and recovering GCN5 protein levels in p38IP knockdown cells by ectopic expression of GCN5 efficiently reversed alpha-tubulin hypoacetylation and G2/M arrest. During the G2/M transition, the association of alpha-tubulin with GCN5 increased, and the acetylation of alpha-tubulin reached a peak. Biochemical analyses demonstrated that the interaction between p38IP and GCN5 depended on the p38IP N terminus (1-381 amino acids) and GCN5 histone acetyltransferase domain and bromodomain. The p38IP N terminus could effectively reverse p38IP depletion-induced GCN5 degradation, thus recovering alpha-tubulin acetylation and G2/M progression. p38IP-mediated suppression of GCN5 ubiquitination most likely occurs via nuclear sequestration of GCN5. Our data indicate that the GCN5-SAGA complex is required for G2/M progression, mainly because p38IP promotes the acetylation of alpha-tubulin by preventing the degradation of GCN5, in turn facilitating the formation of the mitotic spindle. PMID- 24220029 TI - Sphingomyelin depletion impairs anionic phospholipid inward translocation and induces cholesterol efflux. AB - The phosphatidylserine (PS) floppase activity (outward translocation) of ABCA1 leads to plasma membrane remodeling that plays a role in lipid efflux to apolipoprotein A-I (apoAI) generating nascent high density lipoprotein. The Tangier disease W590S ABCA1 mutation has defective PS floppase activity and diminished cholesterol efflux activity. Here, we report that depletion of sphingomyelin by inhibitors or sphingomyelinase caused plasma membrane remodeling, leading to defective flip (inward translocation) of PS, higher PS exposure, and higher cholesterol efflux from cells by both ABCA1-dependent and ABCA1-independent mechanisms. Mechanistically, sphingomyelin was connected to PS translocation in cell-free liposome studies that showed that sphingomyelin increased the rate of spontaneous PS flipping. Depletion of sphingomyelin in stably transfected HEK293 cells expressing the Tangier disease W590S mutant ABCA1 isoform rescued the defect in PS exposure and restored cholesterol efflux to apoAI. Liposome studies showed that PS directly increased cholesterol accessibility to extraction by cyclodextrin, providing the mechanistic link between cell surface PS and cholesterol efflux. We conclude that altered plasma membrane environment conferred by depleting sphingomyelin impairs PS flip and promotes cholesterol efflux in ABCA1-dependent and -independent manners. PMID- 24220030 TI - Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile. AB - Very long-chain fatty acids (VLCFAs, chain length >C20) exist in tissues throughout the body and are synthesized by repetition of the fatty acid (FA) elongation cycle composed of four successive enzymatic reactions. In mammals, the TER gene is the only gene encoding trans-2-enoyl-CoA reductase, which catalyzes the fourth reaction in the FA elongation cycle. The TER P182L mutation is the pathogenic mutation for nonsyndromic mental retardation. This mutation substitutes a leucine for a proline residue at amino acid 182 in the TER enzyme. Currently, the mechanism by which the TER P182L mutation causes nonsyndromic mental retardation is unknown. To understand the effect of this mutation on the TER enzyme and VLCFA synthesis, we have biochemically characterized the TER P182L mutant enzyme using yeast and mammalian cells transfected with the TER P182L mutant gene and analyzed the FA elongation cycle in the B-lymphoblastoid cell line with the homozygous TER P182L mutation (TER(P182L/P182L) B-lymphoblastoid cell line). We have found that TER P182L mutant enzyme exhibits reduced trans-2 enoyl-CoA reductase activity and protein stability, thereby impairing VLCFA synthesis and, in turn, altering the sphingolipid profile (i.e. decreased level of C24 sphingomyelin and C24 ceramide) in the TER(P182L/P182L) B-lymphoblastoid cell line. We have also found that in addition to the TER enzyme-catalyzed fourth reaction, the third reaction in the FA elongation cycle is affected by the TER P182L mutation. These findings provide new insight into the biochemical defects associated with this genetic mutation. PMID- 24220032 TI - Mutant p53 regulates Dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. AB - The control and processing of microRNAs (miRs) is critical in the regulation of all cellular responses. Previous studies have suggested that a reduction in the expression of certain miRs, or an overall decrease in miR processing through the partial depletion of Dicer, can promote enhanced metastatic potential. We show here that Dicer depletion can promote the invasive behavior of cells that is reflected in enhanced recycling and activation of the growth factor receptors Met and EGF receptor. These responses are also seen in response to the expression of tumor-derived mutant p53s, and we show that mutant p53 can down-regulate Dicer expression through both direct inhibition of the TAp63-mediated transcriptional activation of Dicer and a TAp63-independent control of Dicer protein expression. Our results delineate a clear relationship between mutant p53, TAp63, and Dicer that might contribute to the metastatic function of mutant p53 but, interestingly, also reveal TAp63-independent functions of mutant p53 in controlling Dicer activity. PMID- 24220031 TI - Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies. AB - Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases. PMID- 24220033 TI - Structural model for covalent adhesion of the Streptococcus pyogenes pilus through a thioester bond. AB - The human pathogen Streptococcus pyogenes produces pili that are essential for adhesion to host surface receptors. Cpa, the adhesin at the pilus tip, was recently shown to have a thioester-containing domain. The thioester bond is believed to be important in adhesion, implying a mechanism of covalent attachment analogous to that used by human complement factors. Here, we have characterized a second active thioester-containing domain on Cpa, the N-terminal domain of Cpa (CpaN). Expression of CpaN in Escherichia coli gave covalently linked dimers. These were shown by x-ray crystallography and mass spectrometry to comprise two CpaN molecules cross-linked by the polyamine spermidine following reaction with the thioester bonds. This cross-linked CpaN dimer provides a model for the covalent attachment of Cpa to target receptors and thus the streptococcal pilus to host cells. Similar thioester domains were identified in cell wall proteins of other Gram-positive pathogens, suggesting that thioester domains are more widely used and provide a mechanism of adhesion by covalent bonding to target molecules on host cells that mimics that used by the human complement system to eliminate pathogens. PMID- 24220034 TI - Nitric oxide activation of guanylate cyclase pushes the alpha1 signaling helix and the beta1 heme-binding domain closer to the substrate-binding site. AB - The complete structure of the assembled domains of nitric oxide-sensitive guanylate cyclase (NOsGC) remains to be determined. It is also unknown how binding of NO to heme in guanylate cyclase is communicated to the catalytic domain. In the current study the conformational change of guanylate cyclase on activation by NO was studied using FRET. Endogenous tryptophan residues were used as donors, the substrate analog 2'-Mant-3'-dGTP as acceptor. The enzyme contains five tryptophan residues distributed evenly over all four functional domains. This provides a unique opportunity to detect the movement of the functional domains relative to the substrate-binding catalytic region. FRET measurements indicate that NO brings tryptophan 22 in the alphaB helix of the beta1 heme NO binding domain and tryptophan 466 in the second short helix of the alpha1 coiled coil domain closer to the catalytic domain. We propose that the respective domains act as a pair of tongs forcing the catalytic domain into the nitric oxide activated conformation. PMID- 24220036 TI - Philosophy and practice of advance care planning in Scotland. PMID- 24220035 TI - Biosynthesis and expression of a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats-15: a novel versican-cleaving proteoglycanase. AB - The proteoglycanase clade of the ADAMTS superfamily shows preferred proteolytic activity toward the hyalectan/lectican proteoglycans as follows: aggrecan, brevican, neurocan, and versican. ADAMTS15, a member of this clade, was recently identified as a putative tumor suppressor gene in colorectal and breast cancer. However, its biosynthesis, substrate specificity, and tissue expression are poorly described. Therefore, we undertook a detailed study of this proteinase and its expression. We report propeptide processing of the ADAMTS15 zymogen by furin activity, identifying RAKR(212)? as a major furin cleavage site within the prodomain. ADAMTS15 was localized on the cell surface, activated extracellularly, and required propeptide processing before cleaving V1 versican at position (441)E?A(442). In the mouse embryo, Adamts15 was expressed in the developing heart at E10.5 and E11.5 days post-coitum and in the musculoskeletal system from E13.5 to E15.5 days post-coitum, where it was co-localized with hyaluronan. Adamts15 was also highly expressed in several structures within the adult mouse colon. Our findings show overlapping sites of Adamts15 expression with other members of ADAMTS proteoglycanases during embryonic development, suggesting possible cooperative roles during embryogenesis, consistent with other ADAMTS proteoglycanase combinatorial knock-out mouse models. Collectively, these data suggest a role for ADAMTS15 in a wide range of biological processes that are potentially mediated through the processing of versican. PMID- 24220037 TI - Formation of octapod MnO nanoparticles with enhanced magnetic properties through kinetically-controlled thermal decomposition of polynuclear manganese complexes. AB - Polynuclear manganese complexes are used as precursors for the synthesis of manganese oxide nanoparticles (MnO NPs). Altering the thermal decomposition conditions can shift the nanoparticle product from spherical, thermodynamically driven NPs to unusual, kinetically-controlled octapod structures. The resulting increased surface area profoundly alters the NP's surface-dependent magnetism and may have applications in nanomedicine. PMID- 24220038 TI - White matter microstructure changes induced by motor skill learning utilizing a body machine interface. AB - The purpose of this study is to identify white matter microstructure changes following bilateral upper extremity motor skill training to increase our understanding of learning-induced structural plasticity and enhance clinical strategies in physical rehabilitation. Eleven healthy subjects performed two visuo-spatial motor training tasks over 9 sessions (2-3 sessions per week). Subjects controlled a cursor with bilateral simultaneous movements of the shoulders and upper arms using a body machine interface. Before the start and within 2days of the completion of training, whole brain diffusion tensor MR imaging data were acquired. Motor training increased fractional anisotropy (FA) values in the posterior and anterior limbs of the internal capsule, the corona radiata, and the body of the corpus callosum by 4.19% on average indicating white matter microstructure changes induced by activity-dependent modulation of axon number, axon diameter, or myelin thickness. These changes may underlie the functional reorganization associated with motor skill learning. PMID- 24220039 TI - Early attentional processes distinguish selective from global motor inhibitory control: an electrical neuroimaging study. AB - The rapid stopping of specific parts of movements is frequently required in daily life. Yet, whether selective inhibitory control of movements is mediated by a specific neural pathway or by the combination between a global stopping of all ongoing motor activity followed by the re-initiation of task-relevant movements remains unclear. To address this question, we applied time-wise statistical analyses of the topography, global field power and electrical sources of the event-related potentials to the global vs selective inhibition stimuli presented during a Go/NoGo task. Participants (n=18) had to respond as fast as possible with their two hands to Go stimuli and to withhold the response from the two hands (global inhibition condition, GNG) or from only one hand (selective inhibition condition, SNG) when specific NoGo stimuli were presented. Behaviorally, we replicated previous evidence for slower response times in the SNG than in the Go condition. Electrophysiologically, there were two distinct phases of event-related potentials modulations between the GNG and the SNG conditions. At 110-150 ms post-stimulus onset, there was a difference in the strength of the electric field without concomitant topographic modulation, indicating the differential engagement of statistically indistinguishable configurations of neural generators for selective and global inhibitory control. At 150-200 ms, there was topographic modulation, indicating the engagement of distinct brain networks. Source estimations localized these effects within bilateral temporo-parieto-occipital and within parieto-central networks, respectively. Our results suggest that while both types of motor inhibitory control depend on global stopping mechanisms, selective and global inhibition still differ quantitatively at early attention-related processing phases. PMID- 24220040 TI - Detection of optical neuronal signals in the visual cortex using continuous wave near-infrared spectroscopy. AB - Near-infrared spectroscopy (NIRS) measures slow hemodynamic signals noninvasively to indirectly infer the neuronal activity in the brain. However, it remains a controversy on whether this optical measurement technique can detect the optical neuronal signal, which reflects the optical changes directly associated with neuronal activity, within the visual cortex of human and non-human primates. By carefully reviewing the important factors in the detection of optical neuronal signals, we aim to investigate the feasibility of performing NIRS measurements of optical neuronal signals within the visual cortex in humans. To ensure a strong optical neuronal response, a full-field circular black and white reversing checkerboard stimulus was presented, and the reversal frequency was carefully chosen. We used a homemade continuous wave (CW) NIRS system with high detection sensitivity (of the order of 0.1 pW) to record a large area of the visual cortex (approximately 6 * 14 cm(2)). EEG was simultaneously acquired with the optical signal. Based on the mathematical morphology, we adapted the filter proposed by Gratton et al. to remove the influence of arterial pulsation and facilitate the detection and elimination of unknown artifacts from the data. We obtained reliable optical neuronal signals in 77% of the participants (10 out of 13). The amplitudes (latencies) of the obtained optical neuronal signals corresponding to the 785 and 850 nm wavelengths were 0.017 +/- 0.003% (94.7 +/- 8.4 ms) and 0.025 +/- 0.006% (99.0 +/- 7.7 ms), respectively. There were no significant differences between the latencies of the N75 component of the visual evoked potential (VEP) and optical neuronal signals at either wavelength. This is the first study to report optical neuronal signals within the visual cortex in the intact human brain using a CW NIRS system. These results indicate the feasibility of measuring noninvasive optical neuronal signals using a CW NIRS system with high detection sensitivity. PMID- 24220042 TI - Geometric and architectural contributions to hamstring musculotendinous stiffness. AB - BACKGROUND: Greater hamstring musculotendinous stiffness is associated with lesser anterior cruciate ligament loading mechanisms during both controlled joint perturbations and dynamic tasks, suggesting a potential protective mechanism. Additionally, lesser hamstring stiffness has been reported in females, potentially contributing to their greater risk of anterior cruciate ligament injury. However, the factors which contribute to high vs. low stiffness are unclear. Muscle geometry and architecture influence force production and may, therefore, influence stiffness. The purpose of this investigation was to evaluate the contributions of geometric and architectural muscle characteristics to hamstring stiffness. METHODS: Thirty healthy individuals (15 males, 15 females) volunteered for participation. Biceps femoris long head cross-sectional area, pennation angle, fiber length, tendon stiffness, and posterior thigh fat thickness were assessed via ultrasound imaging, and strength was measured via isometric contraction. Stiffness was assessed via the damped oscillatory technique. FINDINGS: Following normalization to anthropometric factors, only strength (r=0.535) and posterior thigh fat thickness (Spearman rho=-0.305) were correlated with stiffness. Normalized tendon stiffness (0.06 vs. 0.10N/m.kg(-1)) and strength (7.1 vs. 10.0N.kg(-1)) were greater in males, while posterior thigh fat thickness (10.4 vs. 5.0mm) was greater in females. INTERPRETATION: Greater posterior thigh fat thickness may influence stiffness by contributing to greater intramuscular fat and shank segment mass, and lesser muscle per unit mass in the thigh segment. These findings suggest that training designed to increase hamstring strength and decrease fat mass may be beneficial for anterior cruciate ligament injury prevention. PMID- 24220041 TI - Neural network of cognitive emotion regulation--an ALE meta-analysis and MACM analysis. AB - Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders. PMID- 24220043 TI - Social media and nutrition education: the food hero experience. AB - Social media can be a quick, low-cost, direct way for nutrition educators to broaden the scope of their targeted programs. The authors' viewpoint is that for social media to be effective, strategies for its use should follow "best practices" guidelines. This viewpoint suggests social media best practices based on experience gained from the Food Hero social marketing campaign. Understanding of how nutrition educators can take advantage of social media as a new mechanism for reaching their target audience is needed, including best practices for implementation, management, and evaluation. PMID- 24220044 TI - Training in methods of preventing childhood obesity increases self-efficacy in nurses in child health services: a randomized, controlled trial. AB - OBJECTIVE: To evaluate the effects of training in methods of preventing childhood obesity on self-efficacy (SE) in nurses. METHODS: In a randomized, controlled trial conducted in child health services in Sweden, nurses in the intervention and control groups of the PRIMROSE prevention trial of childhood obesity were offered a 5-day workshop on dietary and physical activity interventions, and motivational interviewing. Self-efficacy for influencing parents to promote healthy dietary and physical activity behaviors in their children was measured using an 18-item instrument. Difference in SE between groups at post-assessment was analyzed using multiple linear regression analysis. RESULTS: Compared to control nurses (n = 38), intervention nurses (n = 22) demonstrated higher SE (beta = 14.70, P < .001). CONCLUSIONS AND IMPLICATIONS: Training in methods of preventing childhood obesity increased SE in nurses. Self-efficacy should be included as a construct in evaluations of clinical training. PMID- 24220046 TI - Vascularized composite allotransplantation. PMID- 24220045 TI - Parent perspectives on nutrition and physical activity during out-of-school time. AB - OBJECTIVE: Out-of-school time (OST) programs serve a large, diverse population of children, including those at increased obesity risk. In this study, parents' perspectives about nutrition and physical activity (PA) during OST were assessed. DESIGN: Survey. SETTING: Online. PARTICIPANTS: Six hundred parents with a school aged child participating in programs from selected OST organizations. MAIN OUTCOME MEASURES: Parent perspectives about the importance and availability of different foods, beverages, and PA opportunities during OST, and OST program and parent involvement in promoting healthful environments. ANALYSIS: Frequencies were used to describe parents' perspectives. Wilcoxon tests and logistic regression analyses were conducted to test for significant differences. RESULTS: Most parents reported that it was important that their children have water (96.2%), fresh fruits and vegetables (79.0%), and PA (97.2%) during OST; fewer parents reported that these were regularly available. About two thirds of parents agreed that OST programs should promote healthy environments for children, whereas one third agreed that parents alone should be responsible for children's nutrition and PA. CONCLUSIONS AND IMPLICATIONS: Results suggest that many parents would support efforts to improve OST nutrition and PA. Yet, there is a need to further understand the perceptions and motivations of different subgroups to enact successful obesity prevention efforts during OST. PMID- 24220047 TI - Monitoring and long-term outcomes in vascularized composite allotransplantation. AB - PURPOSE OF REVIEW: The field of vascularized composite allotransplantation (VCA) is young, with less than 150 transplants worldwide. However, we now possess as much as 14 years of clinical follow-up. There are similarities and distinct differences between solid-organ transplantation (SOT) and VCA. This review will summarize how VCA recipients are monitored, outcomes observed, and what aspects are unique to VCA. RECENT FINDINGS: Of about 90 documented cases, 10% of VCA recipients are out more than 10 years and 14% are out 5 or more years. There have been both graft losses and patient mortality. In most cases, these losses have been acute, most within the first year, and all within 3 years. Unlike SOT, VCA grafts function well during severe rejection. Chronic rejection-like sequelae are less frequent than in SOT, but do appear. Immunosuppression ranges from standard protocols to novel trials aimed at immunosuppression minimization. Patient selection greatly affects the outcome. Graft loss after year 1 is associated with compliance issues. SUMMARY: Functional outcomes have exceeded expectations. VCA recipients enjoy a quality of life not achievable with conventional reconstruction. Outstanding long-term results of more than a decade have been achieved. Monitoring of VCA patients will require new strategies to incorporate external visualization and effects of environment on rejection. Graft loss has occurred early, suggesting we focus improvement on this time period. More follow up is needed to determine the rates and targets of chronic rejection, and the characteristics of VCA unique to face vs. hand transplantation. PMID- 24220048 TI - Update on infections in composite tissue allotransplantation. AB - PURPOSE OF REVIEW: Several excellent recent reviews have summarized the infectious complications of all composite tissue allograft recipients previously reported. The current review will highlight key management principles derived from these reports. RECENT FINDINGS: Severe Gram-negative infections may occur in the early posttransplant period, particularly Pseudomonas spp. Cytomegalovirus continues to be a major pathogen and is closely linked to allograft rejection; however, some patients have had uncomplicated cytomegalovirus (CMV) episodes. Candida has emerged as a cause of early infections, but the incidence of invasive mold infections has been low. More descriptions of infection risk in the late posttransplant period will be helpful, as more composite tissue allotransplantation recipients survive longer. Newer immunosuppressive regimens may reduce infection risks, but more information will be helpful. SUMMARY: Recent reports have provided expanded information on infections in composite tissue allograft recipients. Centers may choose to broaden the Gram-negative prophylaxis, and to include antifungal prophylaxis directed at Candida spp. CMV prevention protocols should take into account recent reports of CMV outcomes. Future reports should contain infection outcomes in sufficient detail to allow for constructive modifications of antimicrobial management in an era of novel immunosuppression and increasing antimicrobial resistance. PMID- 24220049 TI - Donor and procurement related issues in vascularized composite allograft transplantation. AB - PURPOSE OF REVIEW: To understand the unique requirements of vascularized composite allograft (VCA) donation and procurement practices and the integral role of the established nationwide organ procurement organizations in organ procurement. RECENT FINDINGS: The recent issuance of a Final Rule (July 2013) by the United States Secretary of Health that redefines VCAs as organs rather than tissues, opens up the potential to formalize policies and procedures, under the auspices of the Organ Procurement and Transplantation Network, that can improve VCA donation, procurement practices, develop allocation algorithms and provide transparent oversight. SUMMARY: Improved VCA donation rates, procurement procedures and broader sharing nationwide of VCA donors will have important implications in advancing the emerging field of VCA transplantation. PMID- 24220051 TI - Clinical translation of autologous Schwann cell transplantation for the treatment of spinal cord injury. AB - PURPOSE OF REVIEW: To describe the current status of testing Schwann cell transplantation as a therapy for human spinal cord injury (SCI). RECENT FINDINGS: Transplanted Schwann cells have reparative effects in the damaged spinal cord. A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require immune suppression, but the workload of cell manufacturing is greater. Preclinical Schwann cell transplant studies conducted at the University of Miami in 2009-2012 supported an investigational new drug approved by the Food and Drug Administration. A Phase 1 safety study has been initiated. SUMMARY: Spinal cord repair after severe SCI requires that axonal regeneration and myelination occur in a context of reduced inhibition, enhanced plasticity, and new circuit formation. Evolving clinical experience with Schwann cell transplantation may provide a basis upon which additionally combined therapeutics can be tested to increase the extent of repair after SCI. Safety is the primary consideration when ex-vivo manipulated cells are introduced into the damaged nervous system. Preclinical studies across several species have not indicated safety concerns regarding Schwann cells. Initial clinical reports from studies in Iran and China are suggestive of clinical safety, although more rigorous characterization of the implanted cells is needed. PMID- 24220052 TI - Liver natural killer cell inoculum for liver transplantation with hepatocellular carcinoma. AB - PURPOSE OF REVIEW: Natural killer (NK) cells are innate immune lymphocytes. NK cells contribute to host antimicrobial and antitumor immunity. Liver transplantation in patients with hepatocellular carcinoma (HCC) has increased recently. The possibility of NK cell immunotherapy for liver cancer has been studied. RECENT FINDINGS: Adoptive transfer of interleukin-2 (IL-2)-stimulated NK cells extracted from donor liver perfusate could increase an antitumor response without causing toxicity against 1-haplotype identical recipient intact tissues in patients with live donor liver transplant. Donor liver NK cells showed the most vigorous cytotoxicity against an HCC after in-vitro IL-2 stimulation, compared with donor and recipient peripheral blood NK cells and recipient liver NK cells. IL-2 stimulation led to an increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on liver NK cells. T-cell contamination and risk of graft-versus-host disease can be minimized with a T cell depleting agent such as anti-CD3 antibody. SUMMARY: Allogeneic NK cells might have an advantage for adoptive immunotherapy. Liver NK cells from a deceased donor liver can be used safely as adoptive immunotherapy under current good manufacturing practice conditions for the treatment of liver transplantation with HCC. IL-2-stimulated liver NK cells have strong cytotoxicity, express TRAIL and secret interferon-gamma. PMID- 24220050 TI - Mesenchymal stromal (stem) cells to improve solid organ transplant outcome: lessons from the initial clinical trials. AB - PURPOSE OF REVIEW: Discuss the recent progress on the clinical use of mesenchymal stromal (stem) cells (MSC) in solid organ transplantation (SOT). RECENT FINDINGS: Tissue repair and immunomodulatory properties have been recognized for MSC obtained from different human tissues. MSC-based therapy has been proposed to reduce ischemia-reperfusion injury and to promote immune tolerance. The results of recent clinical trial support the safety and promising effects of autologous and allogeneic MSC in SOT. Collectively, the use of MSC in recipients of living donor kidney transplantation was associated with improved graft function, reduced rejection, ability to omit induction and/or lower maintenance immunosuppression regimen, as well as to treat rejection episodes. SUMMARY: We are living in very exciting times with the implementation of novel clinical trials aimed at establishing safety, feasibility and efficacy of cellular therapies including MSC to improve SOT outcomes. The results of the initial clinical trials support the safety of MSC-based therapy and justifying cautious optimism for the immediate future. PMID- 24220054 TI - 18F-fluorodeoxyglucose PET/computed tomography and risk stratification after neoadjuvant treatment in esophageal cancer patients. AB - OBJECTIVES: The aim of the study was to evaluate the prognostic value of F fluorodeoxyglucose PET/computed tomography (CT) after neoadjuvant therapy (NAT) in locally advanced esophageal cancer (EC) patients. MATERIALS AND METHODS: We recruited 79 EC patients from a sample of 210 who underwent F-fluorodeoxyglucose PET/CT after NAT and who did not have evidence or suspicion of distant metastases. All patients were followed up for a median period of 18 months (range: 2-53 months) from nuclear imaging. PET/CT findings were correlated with surgical management and long-term prognosis. The chi-test was used for categorical variables and the Student t-test for continuous data. Survival curves were computed using the Kaplan-Meier method. A P value less than 0.05 was considered statistically significant. RESULTS: Twenty patients (25.3%) had negative PET/CT and 59 (74.7%) had positive PET/CT results after NAT. Of the 20 patients with negative PET/CT results, eight underwent radical-intent surgery and 12 did not, whereas of the 59 patients with positive PET/CT 44 were scheduled for surgery and 15 were not (P<0.05). On follow-up, 38 patients were seen to be disease free, whereas 23 had relapsed and 15 had died. The overall survival was different between patients with negative PET/CT and those with positive PET/CT scans (98 vs. 40%; P=0.019). Event-free survival was higher in patients with negative PET/CT than in those with positive PET/CT after NAT (78 vs. 0%; P=0.003). Considering patients with positive PET/CT, in the nonsurgical group only three patients were alive without evidence of disease, whereas in the surgical group 19 patients were disease free (20 vs. 46%; P<0.001). CONCLUSION: PET/CT is able to stratify the recurrence risk of EC patients. After a median follow-up period of 18 months, 91% of patients with negative PET/CT scans who did not undergo surgery were seen to be disease free. A positive PET/CT after NAT should be followed by surgery for improving event-free survival. PMID- 24220055 TI - Comparison between anatomical cross-sectional imaging and 18F-FDG PET/CT in the staging, restaging, treatment response, and long-term surveillance of squamous cell head and neck cancer: a systematic literature overview. AB - The outcome of head and neck squamous cell cancer depends primarily on its prompt diagnosis and treatment. Unfortunately, in many cases ominous prognostic factors such as lymph node metastases or osteomandibular extension are present at the time of diagnosis. We review the relative efficacy of contrast-enhanced computed tomography (ceCT), MRI, and F-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in the early detection of head and neck squamous cell cancer, as well as its impact on treatment management and outcomes. Medline and Web of Knowledge databases, from 2000 to January 2013, were evaluated. Ninety-seven reports were selected, but only 11 studies comparing PET or PET/CT with CT and 11 comparing PET or PET/CT with MRI were found appropriate for analysis. ceCT and MRI continue to be the reference imaging modalities for the study of primary tumors, especially in the evaluation of the extension of disease and its relationship with nearby anatomical structures. There is increasing evidence that F-FDG PET/ceCT can provide accurate anatomical details similar to ceCT alone, as well as accurate information on osteomandibular tumor invasion similar to MRI. The major advantage of PET/CT over other imaging methods is its ability to detect relatively small lymph node metastases located in difficult-to-interpret positions. PET/CT is also highly sensitive for the detection of distant metastases and in assessing the response to chemotherapy or chemoradiation treatment and in predicting outcome. ceCT and MRI are the gold standards for evaluating primary and osteomandibular tumoral infiltration. F-FDG PET/CT plays a major role in the detection of lymph node and distant metastases, in assessing the response to neoadjuvant/adjuvant chemotherapy or chemoradiation therapy, and in predicting outcome. PMID- 24220056 TI - Occupational chronic obstructive pulmonary disease: a systematic literature review. AB - OBJECTIVE: Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population wide and industry-specific exposures. METHODS: We used PubMed and Embase to identify relevant original epidemiological peer-reviewed articles, supplemented with citations identified from references in key review articles. This yielded 4528 citations. Articles were excluded for lack of lung function measurement, insufficient occupational exposure classification, lack of either external or internal referents, non-accounting of age or smoking effect, or major analytic inadequacies preventing interpretation of findings. A structured data extraction sheet was used for the remaining 147 articles. Final inclusion was based on a positive qualitative Scottish Intercollegiate Guidelines Network (SIGN) score (>=2+) for study quality, yielding 25 population-wide and 34 industry/occupation specific studies, 15 on inorganic and 19 on organic dust exposure, respectively. RESULTS: There was a consistent and predominantly significant association between occupational exposures and COPD in 22 of 25 population-based studies, 12 of 15 studies with an inorganic/mineral dust exposure, and 17 of 19 studies on organic exposure, even though the studies varied in design, populations, and the use of measures of exposure and outcome. A nearly uniform pattern of a dose-response relationship between various exposures and COPD was found, adding to the evidence that occupational exposures from vapors, gas, dust, and fumes are risk factors for COPD. CONCLUSION: There is strong and consistent evidence to support a causal association between multiple categories of occupational exposure and COPD, both within and across industry groups. PMID- 24220057 TI - Intraluminal thrombus thickness is not related to lower concentrations of trace elements in the wall of infrarenal abdominal aortic aneurysms. AB - BACKGROUND: Intraluminal thrombus (ILT) formation plays a significant role in the progression of infrarenal abdominal aortic aneurysms (AAA). Potentially, as ILT thickness increases the availability of trace elements in the aneurysm wall could decrease thereby leading to oxidative stress and intensifying pro-inflammatory cytokine generation. AIM: To determine if thrombus thickness is related to the concentration of trace elements in the wall of infrarenal AAA. PATIENTS AND METHODS: The concentrations of trace elements in the wall of the aneurysm sack and ILT obtained from 19 consecutive patients during surgery for infrarenal AAA were determined using emission spectrometry. RESULTS: The concentrations of magnesium, zinc, manganese, and lead in the wall of AAA were significantly greater than in the ILT. Only the concentration of copper was lower in the AAA wall compared with the thrombus. The concentration of calcium, phosphorus, zinc, lead, copper, and magnesium increased with ILT thickness. The concentrations of no other trace elements in the wall of AAA were found to be related to the ILT thickness. CONCLUSIONS: Intraluminal thrombus thickness is not associated with a lower concentration of trace elements in the wall of the infrarenal AAA. Thus, the intraluminal thrombus participates in the progression of AAA by mechanisms independent of trace element supply to the wall of the aneurysm sack. PMID- 24220058 TI - [Violent injuries: a oppressive feeling expressed in numbers]. PMID- 24220059 TI - [Primary hyperparathyroidism]. PMID- 24220061 TI - [Violence-related injuries in an urban environment-view from an accident and emergency department]. AB - Violence is a growing problem worldwide. In Switzerland, interpersonal violence seems to be an increasing problem as well. The aim of the current study was to describe a comprehensive picture of violence in a swiss city with regard to medical and social aspects. A total of 1740 patients injured by violent crimes between April 2004 and January 2011 were enrolled into this study. Most of them were male. There were no relevant changes regarding the number of within the observation period. However, the proportion of affected females increased. Especially at the weekend, there is a need for preventive measures to reduce the high number of affected patients and the associated costs. PMID- 24220062 TI - [The educational website Dermaguard to prevent the incidence of skin cancer after transplantation]. AB - Solid organ transplant recipients are highly susceptible to skin cancer. The major driving factors are immunosuppressive medication and ultraviolet light. Appropriate sun protection markedly reduces the development of skin cancer. Skin cancer recognized at an early stage can reliably be cured, and fatal outcomes can be prevented. The aim of this work is to educate organ transplant recipients and health care professionals involved in their care, to increase awareness of skin cancer in this high-risk population and thus to optimize the long-term outcome of patients with skin cancer. Our newly developed website provides free access to various educational materials, including leaflets, presentations and interactive elements using edutainment. PMID- 24220063 TI - [Crooked legs- just an aesthetic problem]. AB - Because the lower extremities are weight bearing, malalignment plays a key role in the development of degenerative disease of the joints. This is particularly true as degenerative arthropathy is of mechanical and not inflammatory cause. Deviation of the axis has been shown to alter the load and force distribution in the joint and thereby causing excessive wear. Whether or not a deformity is clinically relevant or not depends on the symptoms, the amount of the deformity and the location of the deformity. Relevant deformities can be treated with orthotics or corrective osteotomies in early stages. In late stages fusions or joint replacement is the mainstay of treatment. PMID- 24220065 TI - [Not Available]. PMID- 24220066 TI - [Not Available]. PMID- 24220068 TI - [CME dermatology 3. Chronic anorectal pain. Lymphogranuloma venereum]. PMID- 24220073 TI - Drug targets for lymphatic filariasis: a bioinformatics approach. AB - This review article discusses the current scenario of the national and international burden due to lymphatic filariasis (LF) and describes the active elimination programmes for LF and their achievements to eradicate this most debilitating disease from the earth. Since, bioinformatics is a rapidly growing field of biological study, and it has an increasingly significant role in various fields of biology. We have reviewed its leading involvement in the filarial research using different approaches of bioinformatics and have summarized available existing drugs and their targets to re-examine and to keep away from the resisting conditions. Moreover, some of the novel drug targets have been assembled for further study to design fresh and better pharmacological therapeutics. Various bioinformatics-based web resources, and databases have been discussed, which may enrich the filarial research. PMID- 24220074 TI - Dispersal of Aedes aegypti: field study in temperate areas using a novel method. AB - BACKGROUND & OBJECTIVES: Since Aedes aegypti was identified as vector of yellow fever and dengue, its dispersal is relevant for disease control. We studied the dispersal of Ae. aegypti in temperate areas of Argentina during egglaying, using the existing population and egg traps. METHODS: Two independent replicas of a unique experimental design involving mosquitoes dispersing from an urbanized area to adjacent non-urbanized locations were carried out and analyzed in statistical terms. RESULTS: We found relationship between stochastic variables related to the egg-laying mosquito activity (ELMA), useful to assess dispersal probabilities, despite the lack of knowledge of the total number of ovipositions in the zone. We propose to evaluate the egg-laying activity as minus the logarithm of the fraction of negative ovitraps at different distances from the buildings. INTERPRETATION & CONCLUSION: Three zones with different oviposition activity were determined, a corridor surrounding the urbanization, a second region between 10 and 25 m and the third region extending from 30 to 45 m from the urbanization. The landscape (plant cover) and the human activity in the area appear to have an influence in the dispersal of Ae. aegypti. The proposed method worked consistently in two different replicas. PMID- 24220075 TI - Larvicidal activity and GC-MS analysis of flavonoids of Vitex negundo and Andrographis paniculata against two vector mosquitoes Anopheles stephensi and Aedes aegypti. AB - BACKGROUND & OBJECTIVES: Development of insect resistance to synthetic pesticides, high operational cost and environmental pollution have created the need for developing alternative approaches to control vector-borne diseases. In the present study, larvicidal activity of flavonoid extracts of different parts of Vitex negundo (Linnaeus) and Andrographis paniculata (Nees) have been studied against the late III or early IV instar larvae of Aedes aegypti and Anopheles stephensi (Liston). METHODS: Flavonoids were extracted from different parts of the selected plants using standard method. Bioassay test was carried out by WHO method for determination of larvicidal activity against mosquitoes. Different compounds of the most active extract were identified by the gas chromatography mass spectrometry (GC-MS) analysis. RESULTS: Flavonoid extract of whole aerial part of A. paniculata was found to be inactive against the selected larvae of Ae. aegypti even at the concentration of 600 ppm, whereas it caused 70% mortality in An. stephensi at the concentration of 200 ppm. Flavonoid extract of flower-buds produced highest mortality (100%) at the concentration of 600 ppm for the late III or early IV instar larvae of Ae. aegypti and at the concentration of 200 ppm for the larvae of An. stephensi. GC-MS analysis of the most active flavonoid extract from flower-buds of Vitex showed 81 peaks. Phenol (26.83% area), naphthalene (4.95% area), 2,3-dihydrobenzofuran (6.79% area), Phenol-2,4-Bis (1,1 dimethyl) (4.49% area), flavones 4'-OH,5-OH,7-di-O-glucoside (0.25% area) and 5 hydroxy- 3,6,7,3',4'-pentamethoxy flavones (0.80% area) were present in major amount. CONCLUSION: Flavonoid extracts from different parts of two selected plants possess larvicidal activity against two selected mosquito species, hence, could be utilized for developing flavonoid-based, eco-friendly insecticide as an alternative to synthetic insecticides. PMID- 24220071 TI - The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis. AB - INTRODUCTION: Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis. METHODS: We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (<= 35.5 degrees C, 35.6-36.5 degrees C, 36.6-37.5 degrees C, 37.6-38.5 degrees C, 38.6-39.5 degrees C, >= 39.6 degrees C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups. RESULTS: Patients with Tb of <= 36.5 degrees C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5 degrees C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb <= 35.5 degrees C when compared with patients with Tb >36.5 degrees C. The 28-day and hospital mortality was significantly higher in patients with Tb <= 36.5 degrees C. The difference in mortality rate was especially noticeable when patients with Tb <= 35.5 degrees C were compared with patients who had Tb of >36.5 degrees C. Although mortality did not relate to Tb ranges of >= 37.6 degrees C as compared to reference range of 36.6-37.5 degrees C, relative risk for 28-day mortality was significantly greater in patients with 35.6-36.5 degrees C and <= 35.5 degrees C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (<= 36.5 degrees C, n = 160) or absence (>36.5 degrees C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock. CONCLUSIONS: In patients with severe sepsis, hypothermia (Tb <= 36.5 degrees C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock. TRIAL REGISTRATION: UMIN-CTR ID UMIN000008195. PMID- 24220072 TI - Evidence of the causal role of human papillomavirus type 58 in an oropharyngeal carcinoma. AB - Persistent human papillomavirus infection (HPV) is recognized as an important etiologic factor for a subset of head and neck squamous cell carcinomas (SCC), especially those arising from the oropharynx. Whereas HPV16 accounts for the majority of HPV DNA-positive oropharyngeal SCC, infections with other mucosal high-risk HPV types are quite rare and biological data demonstrating their causal involvement are insufficient. Here we present the first case of an oropharyngeal SCC driven by HPV type 58. A 69-year-old Caucasian woman presented with an enlarged and firm left tonsil. A computed tomography scan showed a left tonsillar mass, extending to the soft palate and the glossotonsillar sulcus. The patient underwent extended radical tonsillectomy and ipsilateral selective neck dissection. Pathology confirmed an infiltrating, poorly differentiated SCC of the left tonsil with node metastasis (pT2N1). Adjuvant external beam radiation therapy (60 Grays (Gy)) was administered. After 1 year of follow-up, the patient is well with no evidence of cancer recurrence. HPV analyses of the tumor tissue by BSGP5+/6+ -PCR/MPG, targeting 51 mucosal HPV types, showed single positivity for HPV type 58. Presence of HPV58 E6*I RNA demonstrated biological activity of the virus in the tumor tissue, and presence of serum antibodies to HPV58 oncoproteins E6 and E7 indicated presence of an HPV58-driven cancer. Overexpression of cellular protein p16INK4a and reduced expression of pRb, two cellular markers for HPV-induced cell transformation, were observed. Exons 4-10 of TP53 showed no mutations or polymorphisms. The presence of HPV58 as single HPV infection in combination with a broad variety of direct and indirect markers of HPV transformation provides comprehensive evidence that this oropharyngeal SCC was driven by HPV58. PMID- 24220076 TI - Spatial correlations of population and ecological factors with distribution of visceral leishmaniasis cases in southwestern Iran. AB - BACKGROUND & OBJECTIVES: Leishmaniasis as a dynamic disease may be markedly influenced by demographic and ecological factors. A geospatial information system study was developed to determine the distribution of visceral leishmaniasis (VL) cases in relation to population, climatic and environmental factors in Fars province, southwest of Iran. METHODS: The dwelling addresses of 217 VL patients were obtained from hospital files. A hazard map produced by unifying buffers (5 km) around nomads travel routes (NTR) was developed to survey the effect of close proximity to NTR on the distribution of VL. Mean annual rainfall (MAR), mean annual temperature (MAT), four months temperature mean (T4), elevation, slope and landcover were climatic and environmental factors that have been analysed. Finally, data of dwelling foci were extracted from maps and analysed using logistic regression models. RESULTS: Close proximity to NTR was the most important factor influenced on the disease distribution. Climatic factors were in second rank. Among them, temperature especially T4 is the most effective variable and rainfall was also shown to be another effective climatic agent. Most cases of VL were reported from temperate and semiarid areas in western and central regions while arid condition was a confined factor. The environmental factor of landcovers including urban, dry farm and thin forest regions was revealed as the third rank effective factor. Altitude importance was only shown when its effect was studied independently from other factors. INTERPRETATION & CONCLUSION: These findings present the distribution of VL in Fars province is influenced by combination of ecological and nomads demographical variables although closeness to NTR and nomads role in distribution and continuance of kala-azar are the most important factors. PMID- 24220077 TI - Positive selection and evolution of dengue type-3 virus in the Indian subcontinent. AB - BACKGROUND: Dengue virus infection has recently taken endemic proportions in India with dengu type-3 (DEN-3) as a predominant serotype. In this study, we carried out the selection pressure analysis of three critical immunogenic regions of DEN-3. Phylogenetic analysis was then carried out on the positively selected genomic region in the DEN-3 virus strains isolated in the Indian subcontinent over a time span of 25 yr (1984-2008). Bayesian Markov chain Monte Carlo (MCMC) calculation of the substitution rate was carried out for the DEN-3 genotype-III sequences. METHODS: Sequences corresponding to the C-prM, E-NS1 and NS1 sequence regions of DEN-3 strains were taken for the positive selection analysis. The C prM junction sequences were then used to construct a maximum likelihood (ML) phylogenetic tree. Substitution rates were also calculated under various models of population growth. RESULTS: It was found that codon 86, corresponding to a conserved arginine residue in a crucial T-cell epitope of the C-protein was under significant positive selection. The K86R substitution was found to exist in almost all the Indian strains isolated after 2004. The ML tree constructed from the C-prM junction sequences indicated that strains from the 2006 dengue incidences in Delhi, namely: 04/03/del2006, 05/03/del2006, and 06/03/del2006 were the most rapidly evolving. Substitution rates of a DEN-3 genotype-III sequences from the Indian subcontinent were found to be ~3.0 times higher than those reported from other parts of the world. CONCLUSION: Positive selection in the codon corresponding to R86 of the highly conserved surface C-protein is important in view of its occurrence in a T-cell epitope as well as its strict conservation in all the DEN strains. Phylogenetic analysis of the C-prM junction sequences showed that three strains of 2006 are rapidly evolving. These results were also supported by calculations of the substitution rates. Their significance in the expansion of viral epidemics requires to be investigated. PMID- 24220078 TI - Genotyping of MSP3beta gene in Indian Plasmodium vivax. AB - BACKGROUND & OBJECTIVES: The search for effective polymorphic markers in Plasmodium vivax is highly demanding to understand its transmission in a population. Due to the limited knowledge existing for P. vivax, the search for polymorphic markers for population studies is ongoing. The MSP gene family of Plasmodia has been linked with immune evasion. To study the circulating parasite population P. vivax merozoite surface protein 3beta (PvMSP3beta) polymorphic marker was used to investigate the genetic diversity of P. vivax in natural infections. METHODS: Polymorphism of PvMSP3beta gene was determined in 46 P. vivax blood samples from six different regions of India by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) with PstI. RESULTS: Two different parasite genotypes, viz. type-A and type-B were detected among 46 samples that were positive for PCR, based on the size of the amplification. RFLP analysis with PstI showed 22 allelic groups and 15.2% samples revealed mixed infections on analysis. CONCLUSION: PvMSP3beta was found to be an effective molecular marker for P. vivax as it shows high diversity in India and multiple genotypes easily distinguishable without the need for sequencing. PMID- 24220079 TI - Aedes albopictus in northeast Mexico: an update on adult distribution and first report of parasitism by Ascogregarina taiwanensis. AB - BACKGROUND & OBJECTIVES: Aedes albopictus has been known as efficient vector of dengue in Asian countries and its wide displacement of Ae. aegypti has been documented in many parts of the world. The present survey was carried out to update the distribution of Ae. albopictus in northeast Mexico and to report the first record of parasitism of mosquitoes by Ascogregarina taiwanensis in Mexico. METHODS: Human landing collections were conducted in the month of May every year between 2007 and 2009 across the three states, Nuevo Leon (NL), Tamaulipas and Coahuila in northeast Mexico. Six human bait collections were also organized at the cemetery of Gomez Farias (GF), a village in southern Tamaulipas during the rainy and dry seasons in 2010. Aedes albopictus caught in 2010 were dissected for parasitic protozoan gregarines. RESULTS: The results of human landing collections carried out during 2007-10 across the three states of northeast zone of Mexico revealed that Ae. albopictus is invading along the route between Monterrey City in NL and Tampico, Tamaulipas, but not into the arid state of Coahuila. Aedes albopictus was recorded in nine new municipalities in addition to the 15 municipalities reported before 2005. Furthermore, six human-bait collections performed during the dry and rainy seasons in 2010 at the cemetery of GF suggest the exclusion of Ae. aegypti on that site. Dominance was shared by Ae. quadrivittatus, another container-inhabitant but indigenous species, and Ae. albopictus during the dry and rainy seasons, respectively. The results of dissection of the mosquitoes for gregarines revealed the parasitism of Ae. albopictus by A. taiwanensis. INTERPRETATION & CONCLUSION: The results of this study showed that Ae. albopictus has spread to all the municipalities in the northeastern Mexico except the arid area and reported the first record of parasitic protozoan A. taiwanensis in Mexico. We recommend further studies on larval and adult populations of natural container-occupant mosquitoes in northeastern Mexico in order to have a better documentation of the impact of Ae. albopictus upon the indigenous species community, and its epidemiological role in dengue transmission. PMID- 24220080 TI - Field efficacy and acceptability of PermaNet(r) 3.0 and OlysetNet(r) in Kinshasa, Democratic Republic of the Congo. AB - BACKGROUND & OBJECTIVES: Insecticide resistance in mosquitoes at Kinshasa may jeopardize the efficacy and usage of long-lasting insecticidal nets (LLINs). Entomological impact, user acceptance and bioefficacy of a combination LLIN (PermaNet(r) 3.0) and a standard LLIN (OlysetNet(r)) were evaluated at two sites in Kinshasa characterized by high densities of either Anopheles gambiae s.s. (Kindele) or Culex spp (Kimbangu). METHODS: Insecticide susceptibility (permethrin, deltamethrin, bendiocarb, propoxur and DDT) was determined via tube tests and bottle assays. Entomological impact of unwashed and washed LLINs and untreated nets was assessed via Latin square, based on rotation of nets and their users through selected houses at each site. User acceptability was evaluated through interviews using a questionnaire and net bioefficacy was measured via cone bioassays with field-derived An. gambiae s.s. RESULTS: The An. gambiae s.s. population from Kindele was resistant to DDT and permethrin with mortality rate of 27.3 and 75.8%, respectively, and kdr mutations (L1014F) plus suspected metabolic resistance. The Culex spp population was resistant to all five insecticides tested. No differences in entomological indices were observed for the five net treatments, but bioefficacy against An. gambiae was significantly higher for unwashed and washed PermaNet 3.0 (100 and 71% mortality) than for OlysetNet (56 and 36%). Householders reported a good sleep most often when using unwashed and washed PermaNet (94 and 88%) and least often with unwashed OlysetNet (46%). INTERPRETATION & CONCLUSION: High bioefficacy via cone bioassays against an An. gambiae s.s. population with kdr and suspected metabolic resistance was observed with PermaNet 3.0. Lower biting rates and a higher chance of a good night of sleep were reported when using PermaNet 3.0 compared to OlysetNet. PMID- 24220081 TI - Physicochemical characteristics of habitats in relation to the density of container-breeding mosquitoes in Asom, India. AB - BACKGROUND & OBJECTIVES: Container-breeding mosquitoes, especially Aedes spp are vectors of diseases such as dengue and chikungunya. The abundance of these disease vectors in an area depends on the availability of container habitats and their physicochemical characteristics. The species composition of container breeding mosquitoes in Asom, India was studied and the larval density was correlated with the habitat characteristics. METHODS: Natural and man-made water holding containers in Sonitpur district of Asom were surveyed for the presence of mosquito larvae. The percent composition of container-breeding mosquitoes and container index were calculated. The physicochemical characteristics of breeding water such as pH, conductivity, salinity, total dissolved solids, turbidity and dissolved oxygen were measured. RESULTS: Aedes albopictus (93.7%) was the predominant species in the container-breeding habitats whereas Culex quinquefasciatus (2.77%), Armigeres subalbatus (2.26%), Ae. aegypti (0.76%), Toxorhynchites sp (0.4%) and Lutzia sp (0.11%) were recorded in relatively low numbers. The larval density (mean +/- SEmean) of the container breeding mosquitoes ranged from 4.4 +/- 1.8 to 15.4 +/- 8.2, while the container index ranged from 1.58 to 5.68%. The mean (+/- SEmean) pH, conductivity, salinity, total dissolved solids, turbidity, and dissolved oxygen of water in the container habitats were 7.15 +/- 0.11; 396.1 +/- 58.5 MUS/cm; 0.24 +/- 0.04 ppt; 207.1 +/- 30.4 mg/l; 32.3 +/- 5.1 NTU; and 1.42 +/- 0.12% respectively. The mosquito larval density in the container habitats was having significant negative correlation with the conductivity of breeding water (r = - 0.89; p = 0.003). Salinity, total dissolved solids and turbidity of water in the habitats were negatively correlated, whereas pH and dissolved oxygen were positively correlated with the larval density. INTERPRETATION & CONCLUSION: The studies indicated the predominance of Ae. albopictus in the container-breeding habitats and reiterated its importance as a potential vector of dengue and chikungunya in the region. The spread of Ae. aegypti, the principal vector of dengue, in the semi-urban areas probably through road transport is a matter of public health concern. The use of conductivity of breeding water as an index for the proliferation of container breeding mosquitoes in the region could be explored further. PMID- 24220082 TI - Altitude, temperature, and malaria vectors in Nainital and Udham Singh Nagar districts of Uttarakhand, India: an evidence-based study. AB - BACKGROUND & OBJECTIVES: The relationship between altitude, temperature and malaria are poorly understood. Hence, a study was undertaken at three sites of Udham Singh Nagar (erstwhile Nainital district) and Nainital district (Uttarakhand) during 2010- 11 for the generation of evidences in the context of potential threat of climate change. METHODS: Data on temperature and relative humidity (RH) were recorded through data-logger device in study villages at the altitudes of 166, 226 and 609 m were selected for detailed work. Mosquito collections were made fortnightly during 0600- 0800 hrs. Malaria incidence data were procured from concerned Primary Health Centres. RESULTS: The study provides evidences of decrease in temperature with increase in altitude, even within a district resulting in variation in temporal distribution of malaria vector. With the increase of 67 m altitude between plains and foothill village, there was a reduction in temperature to the tune of 1.1 degrees C and with further increase in altitude of 416 m between foothill and hilly villages, the temperature decreased by 0.27 degrees C. The difference in temperature at three altitudes affects the Transmission windows (TWs) of both Plasmodium vivax (Pv) and P. falciparum (Pf), and opening of TWs are inversely proportional to altitude. In the plains, the TW for Pv and Pf were open for 11 and 10 months respectively, while 10 and 9 months in the foothills and 9 and 8 months, respectively for both the parasites at hilly altitude. Comparison of malaria vectors in plains, foothills, and hilly villages showed that the availability of Anopheles culicifacies and An. fluviatilis decreased with an increase in altitude from foothills to hilly areas. INTERPRETATION & CONCLUSION: This study may be extrapolated to know the suitability of occurrence of malaria vectors and transmission of parasites at different altitudes from the viewpoint of temperature as limiting factor in unknown areas. PMID- 24220083 TI - Synthesis, characterization and evaluation of nanoparticles of public health larvicides for mosquito control. PMID- 24220084 TI - Japanese encephalitis virus isolation from mosquitoes during an outbreak in 2011 in Alappuzha district, Kerala. PMID- 24220085 TI - Cardiac involvement in malaria: an overlooked important complication. PMID- 24220086 TI - Reversible myelopathy in Plasmodium vivax malaria: report of a case and review of literature. PMID- 24220087 TI - Introgressive hybridization as a promoter of genome reshuffling in natural homoploid fish hybrids (Cyprinidae, Leuciscinae). AB - Understanding the mechanisms underlying diversification and speciation by introgressive hybridization is currently one of the major challenges in evolutionary biology. Here, the analysis of hybridization between two pairs of Iberian Leuciscinae provided new data on independent hybrid zones involving Achondrostoma oligolepis (AOL) and Pseudochondrostoma duriense (PDU), and confirmed the occurrence of hybrids between AOL and Pseudochondrostoma polylepis (PPO). A multilevel survey combining morphological, genetic and cytogenomic markers on a vast population screening successfully sorted the selected fishes as admixed. Results were similar in both AOL * PDU and AOL * PPO systems. Overall, hybrid morphotypes, cytogenomic data and genetic profiling indicated preferential backcrossing and suggested AOL as a major genomic contributor. Moreover, results implied AOL as more permissive to introgression than PDU or PPO. Although PDU- and PPO-like individuals appeared more resilient to genome modifications, AOL appeared to be more involved and affected by the ongoing hybridization events, as chromosomal translocations were only found in AOL-like individuals. All hybrids analysed evidenced extensive ribosomal DNA (rDNA) polymorphism that was not found in parental species, but usually seen falling within the range of possible parental combinations. Yet, transgressive phenotypes that cannot be explained by normal recombination, including more rDNA clusters than expected or the occurrence of syntenic rDNAs, were also detected. Present results proved rapid genomic evolution providing the genetic novelty for species to persist. In addition, although the ultimate consequences of such apparently extensive and recurrent events remain unknown, modern genome-wide methodologies are of great promise towards answering questions concerning the causes, dynamics and impacts of hybridization. PMID- 24220088 TI - Genetic differentiation and species cohesion in two widespread Central American Begonia species. AB - Begonia is one of the ten largest plant genera, with over 1500 species. This high species richness may in part be explained by weak species cohesion, which has allowed speciation by divergence in allopatry. In this study, we investigate species cohesion in the widespread Central American Begonia heracleifolia and Begonia nelumbiifolia, by genotyping populations at microsatellite loci. We then test for post-zygotic reproductive barriers using experimental crosses, and assess whether sterility barriers are related to intraspecific changes in genome size, indicating major genome restructuring between isolated populations. Strong population substructure was found for B. heracleifolia (FST=0.364, F'ST=0.506) and B. nelumbiifolia (FST=0.277, F'ST=0.439), and Bayesian admixture analysis supports the division of most populations into discrete genetic clusters. Moderate levels of inferred selfing (B. heracleifolia s=0.40, B. nelumbiifolia s=0.62) and dispersal limitation are likely to have contributed to significant genetic differentiation (B. heracleifolia Jost's D=0.274; B. nelumbiifolia D=0.294). Interpopulation crosses involving a divergent B. heracleifolia population with a genome size ~10% larger than the species mean had a ~20% reduction in pollen viability compared with other outcrosses, supporting reproductive isolation being polymorphic within the species. The population genetic data suggest that Begonia populations are only weakly connected by gene flow, allowing reproductive barriers to accumulate between the most isolated populations. This supports allopatric divergence in situ being the precursor of speciation in Begonia, and may also be a common speciation mechanism in other tropical herbaceous plant groups. PMID- 24220089 TI - Genetic mapping of two components of reproductive isolation between two sibling species of moths, Ostrinia nubilalis and O. scapulalis. AB - We report the quantitative trait loci (QTL) mapping of reproductive isolation traits between Ostrinia nubilalis (the European corn borer) and its sibling species O. scapulalis (the Adzuki bean borer), focusing on two traits: mating isolation (mi) and pheromone production (Pher). Four genetic maps were generated from two backcross families, with two maps (one chromosomal map and one linkage map) per backcross. We located 165-323 AFLP markers on these four maps, resulting in the identification of 27-31 linkage groups, depending on the map considered. No-choice mating experiments with the offspring of each backcross led to the detection of at least two QTLs for mi in different linkage groups. QTLs underlying Pher were located in a third linkage group. The Z heterochromosome was identified by a specific marker (Tpi) and did not carry any of these QTLs. Finally, we considered the global divergence between the two sibling species, distortions of segregation throughout the genome, and the location and effect of mi and Pher QTLs in light of the known candidate genes for reproductive isolation within the genus Ostrinia and, more broadly, in phytophagous insects. PMID- 24220091 TI - RNA Bricks--a database of RNA 3D motifs and their interactions. AB - The RNA Bricks database (http://iimcb.genesilico.pl/rnabricks), stores information about recurrent RNA 3D motifs and their interactions, found in experimentally determined RNA structures and in RNA-protein complexes. In contrast to other similar tools (RNA 3D Motif Atlas, RNA Frabase, Rloom) RNA motifs, i.e. 'RNA bricks' are presented in the molecular environment, in which they were determined, including RNA, protein, metal ions, water molecules and ligands. All nucleotide residues in RNA bricks are annotated with structural quality scores that describe real-space correlation coefficients with the electron density data (if available), backbone geometry and possible steric conflicts, which can be used to identify poorly modeled residues. The database is also equipped with an algorithm for 3D motif search and comparison. The algorithm compares spatial positions of backbone atoms of the user-provided query structure and of stored RNA motifs, without relying on sequence or secondary structure information. This enables the identification of local structural similarities among evolutionarily related and unrelated RNA molecules. Besides, the search utility enables searching 'RNA bricks' according to sequence similarity, and makes it possible to identify motifs with modified ribonucleotide residues at specific positions. PMID- 24220090 TI - Intertwined pathways for Argonaute-mediated microRNA biogenesis in Drosophila. AB - Although Dicer is essential for general microRNA (miRNA) biogenesis, vertebrate mir-451 is Dicer independent. Instead, its short pre-miRNA hairpin is 'sliced' by Ago2, then 3'-resected into mature miRNAs. Here, we show that Drosophila cells and animals generate functional small RNAs from mir-451-type precursors. However, their bulk maturation arrests as Ago-cleaved pre-miRNAs, which mostly associate with the RNAi effector AGO2. Routing of pre-mir-451 hairpins to the miRNA effector AGO1 was inhibited by Dicer-1 and its partner Loqs. Loss of these miRNA factors promoted association of pre-mir-451 with AGO1, which sliced them and permitted maturation into ~ 23-26 nt products. The difference was due to the 3' modification of single-stranded species in AGO2 by Hen1 methyltransferase, whose depletion permitted 3' trimming of Ago-cleaved pre-miRNAs in AGO2. Surprisingly, Nibbler, a 3'-5' exoribonuclease that trims 'long' mature miRNAs in AGO1, antagonized miR-451 processing. We used an in vitro reconstitution assay to identify a soluble, EDTA-sensitive activity that resects sliced pre-miRNAs in AGO1 complexes. Finally, we use deep sequencing to show that depletion of dicer-1 increases the diversity of small RNAs in AGO1, including some candidate mir-451 like loci. Altogether, we document unexpected aspects of miRNA biogenesis and Ago sorting, and provide insights into maturation of Argonaute-cleaved miRNA substrates. PMID- 24220092 TI - Regional and genotypic differences in intrinsic electrophysiological properties of cerebellar Purkinje neurons from wild-type and dystrophin-deficient mdx mice. AB - Cerebellar subregions are recognized as having specialized roles, with lateral cerebellum considered crucial for cognitive processing, whereas vermal cerebellum is more strongly associated with motor control. In human Duchenne muscular dystrophy, loss of the cytoskeletal protein dystrophin is thought to cause impairments in cognition, including learning and memory. Previous studies demonstrate that loss of dystrophin causes dysfunctional signaling at gamma aminobutyric acid (GABA) synapses on Purkinje neurons, presumably by destabilization of GABAA receptors. However, potential differences in the intrinsic electrophysiological properties of Purkinje neurons, including membrane potential and action potential firing rates, have not been investigated. Here, using a 2*2 analysis of variance (ANOVA) experimental design, we employed patch clamp analysis to compare membrane properties and action potentials generated by acutely dissociated Purkinje neurons from vermal and lateral cerebellum in wild type (WT) mice and mdx dystrophin-deficient mice. Compared to Purkinje neurons from WT mice, neurons from mdx mice exhibited more irregular action potential firing and a hyperpolarization of the membrane potential. Firing frequency was also lower in Purkinje neurons from the lateral cerebellum of mdx mice relative to those from WT mice. Several action potential waveform parameters differed between vermal and lateral Purkinje neurons, irrespective of dystrophin status, including action potential amplitude, slope (both larger in the vermal region), and duration (shorter in the vermal region). Moreover, the membrane potential of Purkinje neurons from the vermal region of WT mice exhibited a significant hyperpolarization and concurrent reduction in the frequency of spontaneous action potentials compared to Purkinje neurons from the lateral region. This regional hyperpolarization and reduction in spontaneous action potential frequency was abolished in mdx mice. These results from mice demonstrate the presence of differential electrophysiological properties between Purkinje neurons from different regions of the WT mouse cerebellum and altered intrinsic membrane properties in the absence of dystrophin. These findings provide a possible mechanism for the observations that absence of cerebellar dystrophin contributes to deficits in mental function observed in humans and mouse models of muscular dystrophy. Moreover, these results highlight the importance of distinguishing functional zones of the cerebellum in future work characterizing Purkinje neuron electrophysiology and studies using the model of dissociated Purkinje neurons from mice. PMID- 24220093 TI - Ageing: a little bit of stress does you good. PMID- 24220095 TI - Adolescent anxiety and aggression can be differentially predicted by electrocortical phase reset variables. AB - Increasing evidence supports the notion that both internalizing (e.g., anxiety) and externalizing (e.g., aggression) behavioral dysregulation are associated with abnormal communication between brain regions. Electroencephalographic (EEG) signals across two electrode sites are said to be coherent with one another when they show consistent phase relations. However, periods of desynchrony with shifting of phase relations are a necessary aspect of information processing. The components of EEG phase reset ('locking' when two regions remain in synchrony, and 'shifting' when the two regions desynchronize momentarily) show dramatic changes across development. We collected resting EEG data from typically developing 12 to 15-year-olds and calculated phase shift and lock values in the alpha frequency band across 14 pairs of electrodes varying in inter-electrode distance. A composite measure of participants' aggression levels was positively associated with phase shifting, particularly in the low alpha frequency range, most strongly over the left hemisphere, consistent with the relatively greater left-prefrontal activity reported in aggressive adults. A composite measure of anxiety levels was positively associated with alpha phase locking at sites over both hemispheres, consistent with changes in connectivity reported during anxious thinking in adults. Associations with anxiety could not be explained by traditional EEG coherence measures and suggest that phase shifting and locking might provide an important non-invasive associate of clinically problematic behavior. PMID- 24220096 TI - Novel association between CD74 polymorphisms and hematologic toxicity in patients with NSCLC after platinum-based chemotherapy. AB - BACKGROUND: Platinum-based chemotherapy regimens can cause DNA damage. Macrophage migration inhibitory factor (MIF) plays an important role in the regulation of the cell cycle by either controlling the activity of the SKP1-Cullin/Cdc53-F-box protein ubiquitin ligase (SCF) complex or activating its receptor, CD74. PATIENTS AND METHODS: We used a pathway-based approach to investigate the association between genetic polymorphisms in MIF-pathway genes and the outcomes of platinum based chemotherapy in advanced non-small-cell lung cancer (NSCLC). We used iSelect 24*1 HD BeadChip (Illumina, Inc, San Diego, CA) to genotype 32 tag and potentially functional single nucleotide polymorphisms (SNPs) of 8 selected genes and evaluated their associations with different outcomes for 1004 patients with advanced NSCLC treated with platinum-based chemotherapy. In particular, gastrointestinal toxicity and hematologic toxicity were analyzed for associations with specific genotypes, alleles, and haplotypes. RESULTS: Two polymorphisms of CD74, rs2748249 (C/A) and rs1560661 (A/G), were significantly associated with hematologic toxicity. Carrying an A allele in rs2748249 was associated with higher hematologic toxicity (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.24-2.39; P = .001) and carrying a G allele in rs1560661 was associated with lower hematologic toxicity (OR, 0.42; 95% CI, 0.25-0.70; P = .00099) compared with the wild type. Haplotype analysis revealed that the patients with the CG haplotype (consisting of rs2748249 and rs1560661) had reduced hematologic toxicity compared with patients with other haplotypes (OR, 0.70; 95% CI, 0.56 0.87; P = .0013). The binding domain shared by 3 transcription factors (activator protein-2alpha [AP-2alpha], progesterone response A/B, and TFII-I) comprised the 2 SNPs that may be involved in the regulation of CD74-related B-cell survival. CONCLUSION: Our study is the first to suggest, to our knowledge, that polymorphisms in CD74 might be a marker of lower hematologic toxicity for patients with advanced NSCLC receiving platinum-based chemotherapy. PMID- 24220097 TI - Metastatic melanoma in an esophagus demonstrating Barrett esophagus with high grade dysplasia. AB - BACKGROUND: Metastatic melanoma involving the esophagus is rare; the occurrence of metastatic melanoma in a background of Barrett esophagus is rarer still. We report a case of an 80 year-old male who presented to our institution for workup of Barrett esophagus with high-grade dysplasia and who proved to have metastatic melanoma occurring in the background of Barrett esophagus, the first report of this kind, to our knowledge, in the English literature. CASE PRESENTATION: An 80 year-old Caucasian male was diagnosed at an outside institution with Barrett's esophagus with high grade dysplasia and presented to our institution for therapy. The patient underwent endoscopic mucosal resection using a band ligation technique of an area of nodularity within the Barrett esophagus. Microscopic examination demonstrated extensive Barrett esophagus with high-grade dysplasia as well as a second tumor which was morphologically different from the surrounding high-grade dysplasia and which was positive for S-100, HMB 45 and Melan-A on immunohistochemistry, consistent with melanoma. Further workup of the patient demonstrated multiple radiologic lesions consistent with metastases. Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene. The overall features of the tumor were most consistent with metastatic melanoma occurring in a background of Barrett esophagus with high grade dysplasia. CONCLUSION: This case demonstrates a unique intersection between a premalignant condition (Barrett esophagus with high grade dysplasia) and a separate malignancy (melanoma). This report also shows the utility of molecular testing to support the hypothesis of primary versus metastatic disease in melanoma. PMID- 24220094 TI - The biophysics and cell biology of lipid droplets. AB - Lipid droplets are intracellular organelles that are found in most cells, where they have fundamental roles in metabolism. They function prominently in storing oil-based reserves of metabolic energy and components of membrane lipids. Lipid droplets are the dispersed phase of an oil-in-water emulsion in the aqueous cytosol of cells, and the importance of basic biophysical principles of emulsions for lipid droplet biology is now being appreciated. Because of their unique architecture, with an interface between the dispersed oil phase and the aqueous cytosol, specific mechanisms underlie their formation, growth and shrinkage. Such mechanisms enable cells to use emulsified oil when the demands for metabolic energy or membrane synthesis change. The regulation of the composition of the phospholipid surfactants at the surface of lipid droplets is crucial for lipid droplet homeostasis and protein targeting to their surfaces. PMID- 24220098 TI - Ocular adnexal lymphoma: monitoring response to therapy with diffusion-weighted imaging. AB - PURPOSE: Outcome evaluation in ocular adnexal lymphoma (OAL) is based on clinical assessment and conventional volumetric changes in tumor size. The purpose of this retrospective study was to compare if changes in apparent diffusion coefficient (ADC) tumor values obtained by diffusion-weighted MRI corresponded to changes in enhancing tumor volume in the evaluation of early treatment response or failure in patients with OAL. METHODS: A retrospective case series analysis of conventional contrast-enhanced orbital MRI and diffusion-weighted sequences was performed on 8 pathologically confirmed OAL tumors before and after therapy. Mean ADC values and normalized ADC ratios were obtained using a region-of-interest analysis method on enhancing OAL lesions; tumor volumes were calculated using a manual segmentation method. Changes in tumor volume, mean ADC tumor values, and normalized ADC ratios were compared before and after therapy using a Wilcoxon rank-sum test. RESULTS: Overall, a significant difference was found in mean ADC values and normalized ADC ratios within OAL tumors before and after therapy (p < 0.05), irrespective of the type of therapy administered. There was a trend toward decreased mean enhancing tumor volume after therapy (p = 0.161). An increase in ADC values and a decrease in enhancing tumor volume after therapy correlated with a positive treatment response in 7 of 8 tumors; a decrease in ADC values and an increase in enhancing tumor volume after therapy correlated with a negative treatment response in 1 of 8 tumors. CONCLUSIONS: Tracking changes in tumor ADC values after various treatment regimens for OAL may be useful in predicting early treatment response or failure and can provide complementary information that corresponds to conventional volume changes in tumor size. Further validation of these preliminary results in larger prospective randomized trials is needed. PMID- 24220099 TI - Results of a randomized controlled trial to promote physical activity behaviours in mothers with young children. AB - OBJECTIVE: Increasing levels of physical activity in mothers have long-term health benefits for the mother and family. The study aimed to evaluate the effect of a six-month, physical activity RCT for mothers of young children. METHODS: Women were recruited via playgroups and randomly assigned to intervention (n=394) or control group (n=322). The intervention group received a six-month multi strategy programme delivered via playgroups in Perth, Australia. measures were mean minutes per week of moderate (M) and vigorous (V) intensity physical activity (PA), and number of days/week of muscle strength exercises. RESULTS: The intervention had a significant effect on mean time for vigorous (p=0.008), moderate (p=0.023) and total physical activity (p=0.001) when compared to the control group. The intervention group increased their vigorous activity by a mean of 24min/week, moderate activity by 23min/week and total physical activity by 72min/week. CONCLUSIONS: A relatively minimum home based intervention was able to demonstrate modest but statistically significant improvements in physical activity in a hard to reach group. These changes if maintained over a longer period are likely to improve the health of mothers and have a positive impact on their partners and children. Australian and New Zealand Clinical Trials Registry ACTRN12609000735257. PMID- 24220100 TI - Personal, social and environmental correlates of physical activity in adults from Curitiba, Brazil. AB - BACKGROUND: Leisure-time physical activity is a complex behavior influenced by factors at multiple levels. OBJECTIVE: To examine the associations between intrapersonal, interpersonal, environmental factors and leisure-time walking (LTW) and leisure-time physical activities (LTPA), excluding walking. We also examined the moderating effect of sociodemographic characteristics on these associations. METHODS: A cross-sectional study was conducted with 1461 adults from Curitiba, Brazil (63.7% women). LTW and LTPA were assessed through the International Physical Activity Questionnaire (IPAQ), and a cutoff point of >= 150 min/week was used. Associations were examined through multilevel logistic regressions. RESULTS: LTW was positively associated with self-efficacy, enjoyment, social support from family and friends, presence of public places for leisure and neighborhood esthetics. LTPA was associated with self-efficacy, enjoyment, social support from family and friends, safety from crime and neighborhood esthetics. Safety from crime was a predictor of LTPA among older adults only. CONCLUSIONS: Factors at multiple levels were associated with LTW and LTPA. Interventions to promote LTPA would likely benefit from considering personal, social and environmental factors and different levels of influence. PMID- 24220101 TI - DNA-dependent protein kinase regulates DNA end resection in concert with Mre11 Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM). AB - The resection of DNA double strand breaks initiates homologous recombination (HR) and is critical for genomic stability. Using direct measurement of resection in human cells and reconstituted assays of resection with purified proteins in vitro, we show that DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a classic nonhomologous end joining factor, antagonizes double strand break resection by blocking the recruitment of resection enzymes such as exonuclease 1 (Exo1). Autophosphorylation of DNA-PKcs promotes DNA-PKcs dissociation and consequently Exo1 binding. Ataxia telangiectasia-mutated kinase activity can compensate for DNA-PKcs autophosphorylation and promote resection under conditions where DNA-PKcs catalytic activity is inhibited. The Mre11-Rad50-Nbs1 (MRN) complex further stimulates resection in the presence of Ku and DNA-PKcs by recruiting Exo1 and enhancing DNA-PKcs autophosphorylation, and it also inhibits DNA ligase IV/XRCC4-mediated end rejoining. This work suggests that, in addition to its key role in nonhomologous end joining, DNA-PKcs also acts in concert with MRN and ataxia telangiectasia-mutated to regulate resection and thus DNA repair pathway choice. PMID- 24220102 TI - Integration of molecular and physiological models to explain time of anthesis in wheat. AB - BACKGROUND AND AIMS: A model to predict anthesis time of a wheat plant from environmental and genetic information requires integration of current concepts in physiological and molecular biology. This paper describes the structure of an integrated model and quantifies its response mechanisms. METHODS: Literature was reviewed to formulate the components of the model. Detailed re-analysis of physiological observations are utilized from a previous publication by the second two authors. In this approach measurements of leaf number and leaf and primordia appearance of near isogenic lines of spring and winter wheat grown for different durations in different temperature and photoperiod conditions are used to quantify mechanisms and parameters to predict time of anthesis. KEY RESULTS: The model predicts the time of anthesis from the length of sequential phases: 1, embryo development; 2, dormant; 3, imbibed/emerging; 4, vegetative; 5, early reproductive; 6, pseudo-stem extension; and 7, ear development. Phase 4 ends with vernalization saturation (VS), Phase 5 with terminal spikelet (TS) and Phase 6 with flag leaf ligule appearance (FL). The durations of Phases 4 and 5 are linked to the expression of Vrn genes and are calculated in relation to change in Haun stage (HS) to account for the effects of temperature per se. Vrn1 must be expressed to sufficient levels for VS to occur. Vrn1 expression occurs at a base rate of 0.08/HS in winter 'Batten' and 0.17/HS in spring 'Batten' during Phases 1, 3 and 4. Low temperatures promote expression of Vrn1 and accelerate progress toward VS. Our hypothesis is that a repressor, Vrn4, must first be downregulated for this to occur. Rates of Vrn4 downregulation and Vrn1 upregulation have the same exponential response to temperature, but Vrn4 is quickly upregulated again at high temperatures, meaning short exposure to low temperature has no impact on the time of VS. VS occurs when Vrn1 reaches a relative expression of 0.76 and Vrn3 expression begins. However, Vrn2 represses Vrn3 expression so Vrn1 must be further upregulated to repress Vrn2 and enable Vrn3 expression. As a result, the target for Vrn1 to trigger VS was 0.76 in 8-h photoperiods (Pp) and increased at 0.026/HS under 16-h Pp as levels of Vrn2 increased. This provides a mechanism to model short-day vernalization. Vrn3 is expressed in Phase 5 (following VS), and apparent rates of Vrn3 expression increased from 0.15/HS at 8-h Pp to 0.33/HS at 16-h Pp. The final number of leaves is calculated as a function of the HS at which TS occurred (TS(HS)): 2.86 + 1.1 * TS(HS). The duration of Phase 6 is then dependent on the number of leaves left to emerge and how quickly they emerge. CONCLUSIONS: The analysis integrates molecular biology and crop physiology concepts into a model framework that links different developmental genes to quantitative predictions of wheat anthesis time in different field situations. PMID- 24220104 TI - Post-synthesis reshaping of gold nanorods using a femtosecond laser. AB - This work describes the interaction between femtosecond laser pulses (~130 fs, 800 nm) and gold nanorods (NRs) leading to reshaping of the NRs. We focus on the investigation of structural changes of the NRs and the parameters influencing the reshaping, like surface modification using sodium sulphide, laser power and the position of the longitudinal surface plasmon resonance band (l-SPR) with respect to the laser wavelength. A thermogravimetric analysis experiment is performed to examine changes in the composition of NRs upon heating. A new type of banana shaped NPs is described and the conditions of their appearance are discussed. PMID- 24220103 TI - Population genetic evidence for speciation pattern and gene flow between Picea wilsonii, P. morrisonicola and P. neoveitchii. AB - BACKGROUND AND AIMS: Genetic drift due to geographical isolation, gene flow and mutation rates together make it difficult to determine the evolutionary relationships of present-day species. In this study, population genetic data were used to model and decipher interspecific relationships, speciation patterns and gene flow between three species of spruce with similar morphology, Picea wilsonii, P. neoveitchii and P. morrisonicola. Picea wilsonii and P. neoveitchii occur from central to north-west China, where they have overlapping distributions. Picea morrisonicola, however, is restricted solely to the island of Taiwan and is isolated from the other two species by a long distance. METHODS: Sequence variations were examined in 18 DNA fragments for 22 populations, including three fragments from the chloroplast (cp) genome, two from the mitochondrial (mt) genome and 13 from the nuclear genome. KEY RESULTS: In both the cpDNA and the mtDNA, P. morrisonicola accumulated more species-specific mutations than the other two species. However, most nuclear haplotypes of P. morrisonicola were shared by P. wilsonii, or derived from the dominant haplotypes found in that species. Modelling of population genetic data supported the hypothesis that P. morrisonicola derived from P. wilsonii within the more recent past, most probably indicating progenitor-derivative speciation with a distinct bottleneck, although further gene flow from the progenitor to the derivative continued. In addition, the occurrence was detected of an obvious mtDNA introgression from P. neoveitchii to P. wilsonii despite their early divergence. CONCLUSIONS: The extent of mutation, introgression and lineage sorting taking place during interspecific divergence and demographic changes in the three species had varied greatly between the three genomes. The findings highlight the complex evolutionary histories of these three Asian spruce species. PMID- 24220105 TI - The effects of total sleep deprivation on semantic priming: event-related potential evidence for automatic and controlled processing strategies. AB - There is general consensus that performance on a number of cognitive tasks deteriorates following total sleep deprivation. At times, however, subjects manage to maintain performance. This may be because of an ability to switch cognitive strategies including the exertion of compensatory effort. The present study examines the effects of total sleep deprivation on a semantic word priming task. Word priming is unique because it can be carried out using different strategies involving either automatic, effortless or controlled, effortful processing. Twelve subjects were presented with word pairs, a prime and a target, that were either highly semantically associated (cat...dog), weakly associated (cow...barn) or unassociated (apple...road). In order to increase the probability of the use of controlled processing following normal sleep, the subject's task was to determine if the target word was semantically related to the prime. Furthermore, the time between the offset of the prime and the onset of the target was relatively long, permitting the use of an effortful, expectancy-predictive strategy. Event-related potentials (ERPs) were recorded from 64 electrode sites. After normal sleep, RTs were faster and accuracy higher to highly associated targets; this performance advantage was also maintained following sleep deprivation. A large negative deflection, the N400, was larger to weakly associated and unassociated targets in both sleep-deprived and normal conditions. The overall N400 was however larger in the normal sleep condition. Moreover, a long-lasting negative slow wave developed between the offset of the prime and the onset of the target. These physiological measures are consistent with the use of an effortful, predictive strategy following normal sleep but an automatic, effortless strategy following total sleep deprivation. A picture priming task was also run. This task benefits less from the use of a predictive strategy. Accordingly, in this task, ERPs following the target did not differ as a function of the amount of sleep. PMID- 24220106 TI - Buccal partial pressure of carbon dioxide outweighs traditional vital signs in predicting the severity of hemorrhagic shock in a rat model. AB - BACKGROUND: Hemorrhagic shock (HS) is a leading cause of death in both military and civilian settings. Researchers have investigated different parameters as predictors of HS, but reached inconsistent conclusions. We hypothesized that buccal partial pressure of carbon dioxide (PCO2) was a better predictor of HS than traditional vital signs. MATERIALS AND METHODS: Twenty-four anesthetized Wistar rats were randomly divided into four groups: one control group (no bleeding) and three surgical groups (25%, 35%, and 45% blood loss). Hemorrhage was induced by withdrawing blood from the left femoral artery over a period of 30 min. After that, resuscitation was performed on animals in surgical groups using the Ringer lactate solution. Buccal PCO2 was continuously measured by a newly designed sensor holder during the experiments. Traditional vital signs, cardiac output, base excess, and microvascular perfusion (MPF) were also measured or calculated. RESULTS: Buccal PCO2 differed significantly among four groups beginning at 20 min, approximately 10 min earlier than the shock index and more earlier than the heart rate, systolic blood pressure, and mean arterial pressure. Buccal PCO2 correlated well with cardiac index and the changes in MPF. The correlation coefficients with cardiac index, chest MPF, and upper-limb MPF for buccal PCO2 were 0.781, -0.879, and -0.946, respectively. Besides, buccal PCO2 showed a good value for predicting mortality. Furthermore, an approximate critical threshold of buccal PCO2 was also identified for predicting the severity of HS. CONCLUSIONS: Buccal PCO2 was a noninvasive, sensitive indicator of HS than traditional vital signs and may help on-scene rescuers administer early treatment of injured patients. PMID- 24220107 TI - A novel ribonuclease with antiproliferative activity toward leukemia and lymphoma cells and HIV-1 reverse transcriptase inhibitory activity from the mushroom, Hohenbuehelia serotina. AB - In this study, a 27-kDa ribonuclease (RNase) was purified from the dried fruiting bodies of the mushroom, Hohenbuehelia serotina. The isolation protocol involved anion exchange chromatography, affinity chromatography, cation exchange chromatography and gel filtration in succession. The RNase was unadsorbed on DEAE cellulose, but was adsorbed on Affi-gel blue gel and CM-cellulose. The N-terminal amino acid sequence was TVGGSLAEKGN which showed homology to other fungal RNases to a certain degree. The RNase exhibited maximal RNase activity at pH 5 and 80C. It demonstrated the highest ribonucleolytic activity toward poly(C), a relatively high activity toward poly(U), and a considerably weaker activity toward poly(A) and (G). The RNase inhibited human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with an IC50 of 50 uM and reduced [3H-methyl]-thymidine uptake by L1210 leukemia cells and MBL2 lymphoma cells with an IC50 of 25 uM and 40 uM, respectively. PMID- 24220108 TI - Glycopeptide antibiotic biosynthesis. AB - Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics. PMID- 24220109 TI - Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonization in stambomycin biosynthesis. AB - Many polyketide antibiotics contain macrolactones that arise from polyketide synthase chain release via thioesterase (TE) domain-catalyzed macrolactonization. The hydroxyl groups utilized in such macrolactonization reactions typically derive from reduction of beta-ketothioester intermediates in polyketide chain assembly. The stambomycins are a group of novel macrolide antibiotics with promising anticancer activity that we recently discovered via rational activation of a silent polyketide biosynthetic gene cluster in Streptomyces ambofaciens. Here we report that the hydroxyl group utilized for formation of the macrolactone in the stambomycins is derived from cytochrome P450-catalyzed hydroxylation of the polyketide chain rather than keto reduction during chain assembly. This is a novel mechanism for macrolactone formation in polyketide antibiotic biosynthesis. PMID- 24220110 TI - Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp. AB - A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1-5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis, Bacillus subtilis, Pseudomonas aeruginosa and Burkholderia cepacia. Compounds 2-5 showed varying degrees of activity against human cells, M. tuberculosis and B. subtilis in the low MUM to mid nM range but were inactive against the other strains, while 1 lacking digitoxose was inactive. Very slight structural changes in 2-5 led to varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives. PMID- 24220111 TI - Isolation, structural elucidation and biosynthesis of 3-hydroxy-6 dimethylallylindolin-2-one, a novel prenylated indole derivative from Actinoplanes missouriensis. AB - Many prenylated indole derivatives are widely distributed in nature. Recently, two Streptomyces prenyltransferases, IptA and its homolog SCO7467, were identified in the biosynthetic pathways for 6-dimethylallylindole (DMAI)-3 carbaldehyde and 5-DMAI-3-acetonitrile, respectively. Here, we isolated a novel prenylated indole derivative, 3-hydroxy-6-dimethylallylindolin (DMAIN)-2-one, based on systematic purification of metabolites from a rare actinomycete, Actinoplanes missouriensis NBRC 102363. The structure of 3-hydroxy-6-DMAIN-2-one was determined by HR-MS and NMR analyses. We found that A. missouriensis produced not only 3-hydroxy-6-DMAIN-2-one but also 6-dimethylallyltryptophan (DMAT) and 6 DMAI when grown in PYM (peptone-yeast extract-MgSO4) medium. We searched the complete genome of A. missouriensis for biosynthesis genes of these compounds and found a gene cluster composed of an iptA homolog (AMIS_22580, named iptA-Am) and a putative tryptophanase gene (AMIS_22590, named tnaA-Am). We constructed a tnaA Am-deleted (DeltatnaA-Am) strain and found that it produced 6-DMAT but did not produce 6-DMAI or 3-hydroxy-6-DMAIN-2-one. Exogenous addition of 6-DMAI to mutant DeltatnaA-Am resulted in the production of 3-hydroxy-6-DMAIN-2-one. Furthermore, in vitro enzyme assays using recombinant proteins produced by Escherichia coli demonstrated that 6-DMAI was synthesized from tryptophan and dimethylallyl pyrophosphate in the presence of both IptA-Am and TnaA-Am, and that IptA-Am preferred tryptophan to indole as the substrate. From these results, we concluded that the iptA-Am-tnaA-Am gene cluster is responsible for the biosynthesis of 3 hydroxy-6-DMAIN-2-one. Presumably, tryptophan is converted into 6-DMAT by IptA-Am and 6-DMAT is then converted into 6-DMAI by TnaA-Am. 6-DMAI appears to be converted into 3-hydroxy-6-DMAIN-2-one by the function of some unknown oxidases in A. missouriensis. PMID- 24220112 TI - FeCl3-catalyzed synthesis of functionally diverse dibenzo[b,f]oxepines and benzo[b]oxepines via alkyne-aldehyde metathesis. AB - An efficient synthesis of dibenzo[b,f]oxepines and benzo[b]oxepines via FeCl3 catalyzed alkyne-aldehyde metathesis reaction is described. Structurally diverse dibenzo[b,f]oxepines and benzo[b]oxepines have been achieved in good yields with high regio- and chemoselectivity under mild conditions. Notably, among the various catalysts such as Fe(III), Au(III), In(III), Zn(II), Ag(I) and triflic acid, the alkyne-aldehyde metathesis reaction of 2-(2'-phenylethynyl-phenyloxy) benzaldehyde is only catalyzed by environmentally friendly and sustainable iron(III) chloride. PMID- 24220113 TI - A combination of anatomical and functional evaluations improves the prediction of cardiac event in patients with coronary artery bypass. AB - OBJECTIVE: To study the usefulness of combined risk stratification of coronary CT angiography (CTA) and myocardial perfusion imaging (MPI) in patients with previous coronary-artery-bypass grafting (CABG). DESIGN: A retrospective, observational, single centre study. SETTING AND PATIENTS: 204 patients (84.3% men, mean age 68.7+/-7.6) undergoing CTA and MPI. MAIN OUTCOME MEASURES: CTA defined unprotected coronary territories (UCT; 0, 1, 2 or 3) by evaluating the number of significant stenoses which were defined as the left main trunk >=50% diameter stenosis, other native vessel stenosis >=70% or graft stenosis >=70%. Using a cut-off value with receiver-operating characteristics analysis, all patients were divided into four groups: group A (UCT=0, summed stress score (SSS)<4), group B (UCT>=1, SSS<4), group C (UCT=0, SSS>=4) and group D (UCT>=1, SSS>=4). RESULTS: Cardiac events, as a composite end point including cardiac death, non-fatal myocardial infarction, unstable angina requiring revascularisation and heart-failure hospitalisation, were observed in 27 patients for a median follow-up of 27.5 months. The annual event rates were 1.1%, 2%, 5.7% and 12.9% of patients in groups A, B, C and D, respectively (log rank p value <0.0001). Adding UCT or SSS to a model with significant clinical factors including left ventricular ejection fraction, time since CABG and Euro SCORE II improved the prediction of events, while adding UCT and SSS to the model improved it greatly with increasing C-index, net reclassification improvement and integrated discrimination improvement. CONCLUSIONS: The combination of anatomical and functional evaluations non-invasively enhances the predictive accuracy of cardiac events in patients with CABG. PMID- 24220114 TI - Mortality following a brain tumour diagnosis in patients with multiple sclerosis. AB - OBJECTIVES: As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. SETTING: Hospital inpatients in Sweden with assessment of mortality in hospital or following discharge. PARTICIPANTS: Swedish national registers identified 20 543 patients with an MS diagnosis (1969-2005) and they were matched individually to produce a comparison cohort of 204 163 members of the general population without MS. Everyone with a primary brain tumour diagnosis was selected for this study: 111 with MS and 907 without MS. PRIMARY AND SECONDARY OUTCOME MEASURES: 5-year mortality risk following brain tumour diagnosis and age at brain tumour diagnosis. RESULTS: A non-statistically significant lower mortality risk among patients with MS (lower for those with tumours of high-grade and uncertain-grade malignancy and no notable difference for low-grade tumours) produced an unadjusted HR (and 95% CI) of 0.75 (0.56 to 1.02). After adjustment for age at diagnosis, grade of malignancy, sex, region of residence and socioeconomic index, the HR is 0.91 (0.67-1.24). The change in estimate was largely due to adjustment for age at brain tumour diagnosis, as patients with MS were on average 4.7 years younger at brain tumour diagnosis than those in the comparison cohort (p<0.001). CONCLUSIONS: Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account. PMID- 24220115 TI - Percutaneous endovascular aneurysm repair (PEVAR) - superior to traditional EVAR? PMID- 24220116 TI - State-of-the-art aortic imaging: part I - fundamentals and perspectives of CT and MRI. AB - Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information. PMID- 24220117 TI - Restenosis after infrapopliteal angioplasty - clinical importance, study update and further directions. AB - Patients with critical limb ischemia (CLI) represent the most severe form of peripheral arterial disease (PAD) and exhibit high mortality rates. Frequently, PAD in CLI patients involves the infrapopliteal arterial segment challenging endovascular revascularization strategies. Restenosis remains the major drawback of tibial angioplasty encountered in more than two thirds of CLI patients undergoing tibial revascularization. In contrast to earlier observations, tibial patency was recently shown to be essential to attain an optimal clinical outcome in CLI patients subsequent to tibial angioplasty. The exact pathopyhsiological mechanisms of tibial restenosis remains unclear. To date, most of our knowledge on tibial restenosis and its pathophysiology is derived from coronary arteries, based on the similarity of coronary arteries to tibial artery morphology. Nervertheless, multiple antirestenosis concepts are investigated within clinical trials to reduce tibial restenosis.Purpose of the present manuscript is to provide a current update on the pathophysiology of tibial restenosis and potential antirestenosis strategies. PMID- 24220118 TI - Alpha-linolenic acid intake prevents endothelial dysfunction in high-fat diet-fed streptozotocin rats and underlying mechanisms. AB - BACKGROUND: Endothelial dysfunction is an important factor in the pathogenesis of diabetes related vascular complications, and acute alpha-linolenic acid (ALA) intake can increase flow-mediated dilation of the diabetic artery at 4 h postprandially. However, whether chronic ALA supplementation may prevent endothelial dysfunction in the process of diabetes and underlying mechanisms remains largely unknown. MATERIALS AND METHODS: The high-fat diet-fed streptozotocin (HFD-STZ) rats provided an animal model for T2DM. Age-matched normal and HFD-STZ rats randomly received normal diet or ALA (500 mg/kg per day). After 5 weeks of feeding, endothelial function was determined. RESULTS: Diabetes caused significant endothelial dysfunction (maximal vasorelaxation responses to ACh) in aortic segments, and ALA intake alleviated endothelial dysfunction. Superoxide production and peroxynitrite (ONOO-) formation were reduced with ALA supplement in diabetic vascular segments. Interestingly, ALA intake enhanced eNOS but inhibited iNOS activity in diabetic vessels. Moreover, ALA intake significantly increased eNOS phosphorylation. On the other hand, gp91phox and iNOS overexpression were reduced moderately with ALA intake in diabetic vessels. CONCLUSIONS: We concluded that ALA prevents diabetes-induced endothelial dysfunction by enhancing eNOS activity and attenuates oxidative/nitrative stress by inhibiting iNOS and NADPH oxidase expression and ONOO- production. PMID- 24220119 TI - Breast artery calcium noted on screening mammography is predictive of high risk coronary calcium in asymptomatic women: a case control study. AB - BACKGROUND: The relationship between breast artery calcification (BAC) noted on mammography and both coronary artery disease and cardiovascular risk remains controversial. Few studies have examined the clinical significance of BAC in asymptomatic women. In the present study we evaluated the relationship between BAC and coronary artery calcium (CAC) as identified by multi-slice CT scanning (MSCT). PATIENTS AND METHODS: Consecutive women (n = 98) with BAC noted on routine mammography but without known coronary artery disease (CAD) were assessed for CAD risk factors and had assessment of coronary calcium by MSCT. A control cohort of consecutive women who were BAC(-) (n = 104) underwent an identical assessment. RESULTS: Women who were BAC(+) were older than those who were BAC(-); otherwise, there were no differences between the 2 groups with regard to traditional cardiac risk factors. Significantly more BAC(+) vs. BAC(-) women were found to have ?high risk? CAC scores, defined as CAC > 400 (11.2 % vs. 1.0 %, p = 0.006). However, the rates of CAC scores of 0 were not different between the two groups (50.0 % vs. 54.8 % for BAC(+) and BAC(-) , respectively, p = 0.586). When examined in a multivariate model including the traditional risk factors of diabetes, increasing age, smoking, hyperlipidemia, and family history of CAD, the presence of BAC remained significantly associated with CAC > 400 (OR = 22.6, 95 % CI = 2.1 - 237.1). CONCLUSIONS: The presence of breast artery calcium on screening mammography was a strong independent predictor (odds ratio > 22) of high risk coronary artery calcium scores (defined as CAC > 400). The presence of BAC in those with significant CAD risk factors may warrant further evaluation. PMID- 24220120 TI - Percutaneous transluminal angioplasty of infrainguinal vein graft stenosis is not a negative predictor for long-term patency. AB - BACKGROUND: To investigate whether maintenance percutaneous transluminal angioplasty (PTA) for significant stenosis after infrainguinal bypass grafting affects long-term patency of the bypass grafts in comparison to those not needing intervention. PATIENTS AND METHODS: The cohort includes 141 consecutive patients with 157 infrainguinal vein grafts performed from January 1996 to December 2005. Grafts occluded within three months after operation were excluded. Revascularisations needing maintenance PTA for significant stenoses of graft or adjacent in- or outflow vessels (intervention group, n = 39) were compared to those not needing intervention during follow up (non-intervention group, n = 118). Primary end point was bypass occlusion. Secondary end points were major amputation or death. Long-term patency in the intervention and non-intervention groups was estimated using Kaplan-Meier curves and compared using the Tarone-Ware test. RESULTS: In the intervention group, primary assisted patency rate after 36 and 60 months was 94.1 % and 89.4 %, respectively, whereas in the non intervention group patency rate was 92.5 % and 91.0 %, respectively (p = 0.644). Comparing the intervention group to the non-intervention group, 1 versus 2 major amputations (p = 0.642) and 14 versus 40 deaths (p = 0.233) occurred. CONCLUSIONS: Occurrence of graft stenosis did not decrease long-term patency rate when treated by PTA in comparison to grafts not needing maintenance PTA. PMID- 24220121 TI - Outcome after open surgery repair in endovascular-suitable patients with ruptured abdominal aortic aneurysms. AB - BACKGROUND: Endovascular aneurysm repair (EVAR) has been suggested in several studies to be superior to open surgery repair (OSR) for the treatment of ruptured abdominal aortic aneurysms (rAAAs), but this finding might be affected by selection bias based on aneurysm morphology and patient characteristics. We tested rAAA anatomy according to EVAR suitability in patients undergoing OSR to assess the impact on mortality. PATIENTS AND METHODS: This retrospective analysis reports on 83 patients with rAAAs treated between November 2002 and July 2013. Pre-operative computed tomography (CT) scans were evaluated based on EVAR suitability and were determined by blinded independent reviewers. CT scans were lacking due to acquisition in an external institution with no availability (n = 9) or solely ultrasound evaluations (n = 8). In addition patient characteristics and outcomes were assessed. RESULTS: All patients who underwent OSR and who had available preoperative CT scans were included in the study (n = 66). In summary, 42 % of the patients (28/66; 95 % confidence interval [CI], 30.5 - 54.4) were considered eligible for EVAR according to pre-operative CT scans and 58 % of the patients (38/66; 95 % CI, 45.6 - 69.5) were categorized as unsuitable for endovascular repair. Patients suitable for EVAR had a significantly lower prevalence of in-hospital deaths (25 % [7/28]; 95 % CI, 9 - 41) in contrast to patients unsuitable for EVAR (53 % [20/38]; 95 % CI, 36.8 - 68.5; p = 0.02). CONCLUSIONS: EVAR-suitable patients had a highly significant mortality reduction undergoing OSR. Thus, the present study proposes that EVAR suitability is a positive predictor for survival after open repair of rAAA. PMID- 24220122 TI - Lumbar artery aneurysms as a rare cause of life threatening retroperitoneal bleeding. PMID- 24220123 TI - Blood will find its way. Retrograde perfusion of a transplant- kidney via a femoro- femoral crossover bypass. PMID- 24220124 TI - Marfan syndrome and cervical internal carotid artery aneurysm. PMID- 24220125 TI - Venous occlusion due to cystic adventitial degeneration of the common femoral vein. PMID- 24220131 TI - Frontal meningioma mimicking relapse of schizophrenia. PMID- 24220130 TI - Episodes of horizontal gene-transfer and gene-fusion led to co-existence of different metal-ion specific glyoxalase I. AB - Glyoxalase pathway plays an important role in stress adaptation and many clinical disorders. The first enzyme of this pathway, glyoxalase I (GlxI), uses methylglyoxal as a substrate and requires either Ni(II)/Co(II) or Zn(II) for activity. Here we have investigated the origin of different metal ion specificities of GlxI and subsequent pattern of inheritance during evolution. Our results suggest a primitive origin of single-domain Ni dependent GlxI [Ni-GlxI]. This subsequently evolved into Zn activated GlxI [Zn-GlxI] in deltaproteobacteria. However, origin of eukaryotic Zn-GlxI is different and can be traced to GlxI from Candidatus pelagibacter and Sphingomonas. In eukaryotes GlxI has evolved as two-domain protein but the corresponding Zn form is lost in plants/higher eukaryotes. In plants gene expansion has given rise to multiple two domain Ni-GlxI which are differentially regulated under abiotic stress conditions. Our results suggest that different forms of GlxI have evolved to help plants adapt to stress. PMID- 24220132 TI - Comparing profiles of mental disorder across birth cohorts: results from the 2007 Australian National Survey of Mental Health and Wellbeing. AB - OBJECTIVE: To describe and compare individuals with any DSM-IV mental disorder from three different birth cohorts - young (16-34 years), middle age (35-59 years) and older age (60-85 years) - on a range of clinically relevant factors. METHOD: Data were derived from the 2007 Australian National Survey of Mental Health and Wellbeing. Individuals from three birth cohorts with a range of mental health and substance use disorders were identified using DSM-IV criteria and compared using regression analysis. The specific factors that were compared include: (1) type of disorder/disorders present; (2) suicidality; (3) number of co-occurring disorders; (4) levels of distress and impairment; (5) self-assessed physical and mental health; (6) presence of physical conditions; (7) size and quality of social support/network; and (8) treatment-seeking behaviour. RESULTS: The birth cohorts differed dramatically in terms of the specific disorders that were present. The older cohort were significantly more likely to experience internalising disorders and significantly less likely to experience externalising disorders in comparison to the young cohort. The older cohort were significantly more likely to experience co-morbid physical conditions as well as lower life satisfaction, poorer self-rated physical health, increased functional impairment, and more days out of role. The younger cohort had a significantly larger peer group that they could confide in and rely on in comparison to the older cohort. CONCLUSIONS: Clinicians and researchers need to be cognisant that mental disorders manifest as highly heterogeneous constructs. The presentation of a disorder in a younger individual could be vastly different from the presentation of the same disorder in an older individual. The additional burden associated with these factors and how they apply to different birth cohorts must be taken into consideration when planning mental health services and effective treatment for the general population. PMID- 24220133 TI - Do mindfulness-based therapies have a role in the treatment of psychosis? PMID- 24220134 TI - Synaesthesia, reflex hallucinations and Mitempfindung - one of the same or different entities? PMID- 24220135 TI - Is food addiction a valid phenomenon through the lens of the DSM-5? PMID- 24220136 TI - What difference a decade? The costs of psychosis in Australia in 2000 and 2010: comparative results from the first and second Australian national surveys of psychosis. AB - OBJECTIVES: To assess differences in costs of psychosis between the first and second Australian national surveys of psychosis and examine them in light of policy developments. METHOD: Cost differences due to changes in resource use and/or real price rises were assessed by minimizing differences in recruitment and costing methodologies between the two surveys. For each survey, average annual societal costs of persons recruited through public specialized mental health services in the census month were assessed through prevalence-based, bottom-up cost-of-illness analyses. The first survey costing methodology was employed as the reference approach. Unit costs were specific to each time period (2000, 2010) and expressed in 2010 Australian dollars. RESULTS: There was minimal change in the average annual costs of psychosis between the surveys, although newly included resources in the second survey's analysis cost AUD$3183 per person. Among resources common to each analysis were significant increases in the average annual cost per person for ambulatory care of AUD$7380, non-government services AUD$2488 and pharmaceuticals AUD$1892, and an upward trend in supported accommodation costs. These increases were offset by over a halving of mental health inpatient costs of AUD$11,790 per person and a 84.6% (AUD$604) decrease in crisis accommodation costs. Productivity losses, the greatest component cost, changed minimally, reflecting the magnitude and constancy of reduced employment levels of individuals with psychosis across the surveys. CONCLUSIONS: Between 2000 and 2010 there was little change in total average annual costs of psychosis for individuals receiving treatment at public specialized mental health services. However, there was a significant redistribution of costs within and away from the health sector in line with government initiatives arising from the Second and Third National Mental Health Plans. Non-health sector costs are now a critical component of cost-of-illness analyses of mental illnesses reflecting, at least in part, a whole-of-government approach to care. PMID- 24220137 TI - MAT gene idiomorphs suggest a heterothallic sexual cycle in a predominantly asexual and important pine pathogen. AB - Diplodia pinea (=Sphaeropsis sapinea) is a well-known and economically important latent pathogen of Pinus spp. in many parts of the world. Despite intensive scrutiny, its sexual state has never been observed and the fungus has thus been considered exclusively asexual. It was, therefore, surprising that a recent population genetics study showed high genotypic diversity and random association of alleles in a number of populations, suggesting that the pathogen has a cryptic sexual stage. Using the genome sequence of two individual D. pinea isolates, we interrogated the structure of the MAT locus in this fungus. The results suggested that D. pinea is heterothallic (self-sterile) with complete and apparently functional copies of the MAT genes containing the alpha-1 and HMG domains present in different isolates. In addition to the MAT1-2-1 and MAT1-1-1 genes, we found a MAT1-1-4 gene in the MAT1-1 idiomorph and a novel MAT1-2-5 gene in the MAT1-2 idiomorph. Importantly, the frequencies of occurrence of both idiomorphs in populations examined were not significantly different from a 1:1 ratio, which would be expected in sexually reproducing populations. Although the sexual state has never been observed, the results strongly suggest that D. pinea has a cryptic, heterothallic sexual cycle. PMID- 24220138 TI - Impaired standing balance in elderly: a new engineering method helps to unravel causes and effects. AB - Deteriorated balance control is the most frequent cause of falls and injuries in the elderly. Balance control comprises a complex interplay of several underlying systems (ie, the sensory systems, the motor system, and the nervous system). Available clinical balance tests determine the patient's ability to maintain standing balance under defined test conditions and aim to describe the current state of this ability. However, these tests do not reveal which of the underlying systems is deteriorated and to what extent, so that the relation between cause and effect often remains unclear. Especially detection of early-stage balance control deterioration is difficult, because the balance control system is redundant and elderly may use compensation strategies. This article describes a new method that is able to identify causal relationships in deteriorated balance control, called CLSIT (Closed Loop System Identification Technique). Identification of impaired balance with CLSIT is a base for development of tailored interventions and compensation strategies to reduce the often serious consequences of deteriorated balance control in the elderly. PMID- 24220139 TI - Quality of life and quality of care for people with dementia receiving long term institutional care or professional home care: the European RightTimePlaceCare study. AB - OBJECTIVES: To explore how quality of life (QoL) and quality of care (QoC) for people with dementia (PwD) vary across 8 European countries; to explore how QoL and QoC for PwD vary across living arrangements; and to assess the association between QoL and QoC. DESIGN: Cross-sectional survey. SETTING: Institutional long term care and home care in 8 European countries (England, Estonia, Finland, France, Germany, the Netherlands, Spain, and Sweden). PARTICIPANTS: PwD receiving formal home care but at risk for admission to an institutional setting, and PwD who were recently admitted. MEASUREMENTS: QoL was assessed by the PwD and by their best informed proxies using the Quality of Life-Alzheimer's Disease scale (QoL-AD) (range 13-52). QoC was measured using quality of care indicators (eg, the presence of depressive symptoms, the presence of pressure ulcers). RESULTS: A total of 1123 PwD living at home (mean age 82.2, 63%women) and 791 PwD living in institutional care (mean age 84.1, 74% women) participated. QoL of PwD was most often rated highest in Sweden and England and lowest in Estonia and Spain. No differences in QoL were detected among the settings. For the QoC indicators, no consistent patterns were visible in such a way that certain countries or settings scored "higher" or "lower." The presence of depressive symptoms was most consistently associated with lower QoL (P <= .001). CONCLUSION: There is great variation in QoL and QoC scores among European countries and settings. To gain insight into the underlying causes of these differences, more knowledge is needed about the effect of different national health care systems and dementia strategies on QoL and QoC indicators. Depressive symptoms were associated with QoL, and executing longitudinal studies investigating which factors are associated with change in QoL is highly recommended. PMID- 24220140 TI - Acute complications and outcomes of acute head injury in adult patients with haemophilia. AB - The aim of the present study is to describe the clinical and epidemiological characteristics, complications and outcome of patients with haemophilia and acute head injury (AHI) at the emergency department (ED), and develop a protocol to prevent early and late complications. This is a retrospective cohort study including all patients with haemophilia and AHI admitted to the ED. We identified 26 patients with AHI. A computed tomography scan was carried out on all patients at admission, and again on two patients (with neurosurgical complications) 48 h later. The discharge diagnosis was as follows: 3.8% subdural haematoma, 3.8% cerebellar epidural haematoma and 92.3% uncomplicated AHI. We propose the following protocol: a computed tomography scan upon arrival and another within 48 h post-AHI, unless there is an absence of clinical symptoms. In addition, all patients must self-administer a clotting factor as soon as possible and be observed in the ED for at least 48 h. PMID- 24220142 TI - Homogenous mixing of ionic liquids: molecular dynamics simulations. AB - Binary mixtures of room temperature ionic liquids (IL) with a common cation were investigated using atomistic molecular dynamics (MD) simulations. Two different binary ILs, viz., [C4mim][PF6]-[C4mim][Cl] and [C4mim][PF6]-[C4mim][BF4], were studied with varying fractions of either anion. The coordination environment of an anion around the cation is altered in the presence of another type of anion. The extent of change is larger for anions with much different radii. Atomistic MD and coarse grain MD simulations do not show any evidence for the clustering of like anions at any concentration. The binary liquids are well mixed at the molecular level. PMID- 24220141 TI - Impact of MACC1 on human malignant glioma progression and patients' unfavorable prognosis. AB - BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been established as an independent prognostic indicator of metastasis formation and metastasis free survival for patients with colon cancer and other solid tumors. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor of adulthood, and due to its invasive and rapid growth, patients have unfavorable prognoses. Although these tumors rarely metastasize, their invasive and migratory behavior is similar to those of metastatic cells of tumors of different origin. Thus, we hypothesized that MACC1 may be involved in progression of human gliomas. METHODS: We performed real-time measurements of proliferation and migration in MACC1-transfected GBM cell lines (U138, U251) and evaluated tumor formation in organotypic hippocampal slice cultures of mice. Semiquantitative and quantitative real-time reverse transcription PCR analyses were performed for MACC1 and for its transcriptional target c-Met in human astrocytoma of World Health Organization grade II (low-grade astrocytoma) and GBM biopsies. Data were validated by MACC1 immunohistochemistry in independent matched samples of low-grade astrocytoma and GBM. RESULTS: MACC1 increases the proliferative, migratory, and tumor-formation abilities of GBM cells. The c-Met inhibitor crizotinib reduced MACC1-induced migration and tumor formation in organotypic hippocampal slice cultures of mice. Analyzing patients' biopsies, MACC1 expression increased concomitantly with increasing World Health Organization grade. Moreover, MACC1 expression levels allowed discrimination of dormant and recurrent low-grade astrocytomas and of primary and secondary GBM. Strong MACC1 expression correlated with reduced patient survival. CONCLUSIONS: MACC1 may represent a promising biomarker for prognostication and a new target for treatment of human gliomas. PMID- 24220143 TI - Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. AB - OBJECTIVE: The normal cut-off values for hyperandrogenaemia differ between populations. Although there are various ways to determine the normal range of hormones in a population, use of a gold standard and the 95th percentile approach are not appropriate to diagnose hyperandrogenism. This study aimed to determine normative cut-off androgen levels for Iranian women of reproductive age using k means cluster analysis. STUDY DESIGN: The subjects were 1126 women, aged 18-45 years, initially selected at random from women of reproductive age from different geographic regions of Iran. Serum levels of hormones were measured, and complete data were available for 923 women following the implementation of exclusion criteria. The reference group comprised 423 eumenorrhoeic non-hirsute women selected from the total population. Normative cut-off levels were computed using k-means cluster analysis (k=3). Analyses were also conducted based on age and body mass index (BMI) groups for the 923 subjects. RESULTS: Cluster cut-off values for the total study population were similar to the 95th percentile values, whereas the percentiles for the free androgen index, total testosterone, dehydroepiandrostenedione sulphate and androstenedione were 79.3%, 74.1%, 96.7% and 71%, respectively, in the reference group. CONCLUSIONS: Determination of cut off values for hyperandrogenism based on age and BMI categories provides the most objective way of determining normal upper limits of androgen levels among Iranian women of reproductive age. PMID- 24220144 TI - SeqReporter: automating next-generation sequencing result interpretation and reporting workflow in a clinical laboratory. AB - A wide repertoire of bioinformatics applications exist for next-generation sequencing data analysis; however, certain requirements of the clinical molecular laboratory limit their use: i) comprehensive report generation, ii) compatibility with existing laboratory information systems and computer operating system, iii) knowledgebase development, iv) quality management, and v) data security. SeqReporter is a web-based application developed using ASP.NET framework version 4.0. The client-side was designed using HTML5, CSS3, and Javascript. The server side processing (VB.NET) relied on interaction with a customized SQL server 2008 R2 database. Overall, 104 cases (1062 variant calls) were analyzed by SeqReporter. Each variant call was classified into one of five report levels: i) known clinical significance, ii) uncertain clinical significance, iii) pending pathologists' review, iv) synonymous and deep intronic, and v) platform and panel specific sequence errors. SeqReporter correctly annotated and classified 99.9% (859 of 860) of sequence variants, including 68.7% synonymous single-nucleotide variants, 28.3% nonsynonymous single-nucleotide variants, 1.7% insertions, and 1.3% deletions. One variant of potential clinical significance was re-classified after pathologist review. Laboratory information system-compatible clinical reports were generated automatically. SeqReporter also facilitated quality management activities. SeqReporter is an example of a customized and well designed informatics solution to optimize and automate the downstream analysis of clinical next-generation sequencing data. We propose it as a model that may envisage the development of a comprehensive clinical informatics solution. PMID- 24220145 TI - Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts. AB - BACKGROUND: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing. RESULTS: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1) Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis. CONCLUSIONS: This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used. PMID- 24220146 TI - Whole genome sequencing and de novo assembly identifies Sydney-like variant noroviruses and recombinants during the winter 2012/2013 outbreak in England. AB - BACKGROUND: Norovirus is the commonest cause of epidemic gastroenteritis among people of all ages. Outbreaks frequently occur in hospitals and the community, costing the UK an estimated L110 m per annum. An evolutionary explanation for periodic increases in norovirus cases, despite some host-specific post immunity is currently limited to the identification of obvious recombinants. Our understanding could be significantly enhanced by full length genome sequences for large numbers of intensively sampled viruses, which would also assist control and vaccine design. Our objective is to develop rapid, high-throughput, end-to-end methods yielding complete norovirus genome sequences. We apply these methods to recent English outbreaks, placing them in the wider context of the international norovirus epidemic of winter 2012. METHOD: Norovirus sequences were generated from 28 unique clinical samples by Illumina RNA sequencing (RNA-Seq) of total faecal RNA. A range of de novo sequence assemblers were attempted. The best assembler was identified by validation against three replicate samples and two norovirus qPCR negative samples, together with an additional 20 sequences determined by PCR and fractional capillary sequencing. Phylogenetic methods were used to reconstruct evolutionary relationships from the whole genome sequences. RESULTS: Full length norovirus genomes were generated from 23/28 samples. 5/28 partial norovirus genomes were associated with low viral copy numbers. The de novo assembled sequences differed from sequences determined by capillary sequencing by <0.003%. Intra-host nucleotide sequence diversity was rare, but detectable by mapping short sequence reads onto its de novo assembled consensus. Genomes similar to the Sydney 2012 strain caused 78% (18/23) of cases, consistent with its previously documented association with the winter 2012 global outbreak. Interestingly, phylogenetic analysis and recombination detection analysis of the consensus sequences identified two related viruses as recombinants, containing sequences in prior circulation to Sydney 2012 in open reading frame (ORF) 2. CONCLUSION: Our approach facilitates the rapid determination of complete norovirus genomes. This method provides high resolution of full norovirus genomes which, when coupled with detailed epidemiology, may improve the understanding of evolution and control of this important healthcare-associated pathogen. PMID- 24220148 TI - Influence of aeration modes on leachate characteristic of landfills that adopt the aerobic-anaerobic landfill method. AB - As far as the optimal design, operation, and field application of the Aerobic Anaerobic Landfill Method (AALM) are concerned, it is very important to understand how aeration modes (different combinations of aeration depth and air injection rate) affect the biodegradation of organic carbon and the transformation of nitrogen in landfill solid waste. Pilot-scale lysimeter experiments were carried out under different aeration modes to obtain detailed information regarding the influence of aeration modes on leachate characteristics. Results from these lysimeter experiments revealed that aeration at the bottom layer was the most effective for decomposition of organic carbon when compared with aeration at the surface or middle layers. Moreover, the air injection rate led to different nitrogen transformation patterns, unlike the lesser influence it has on organic carbon decomposition. Effective simultaneous nitrification and denitrification were observed for the aeration mode with a higher air injection rate (=1.0 L/min). On the other hand, the phenomenon of sequenced nitrification and denitrification could be observed when a low air injection rate (=0.5L/min.) was employed. Finally, it is concluded that, for AALM, air injection with a higher air injection rate at the deepest layer near the leachate collection pipe tends to accelerate the stabilization of landfill waste as defined in terms of the enhancement of denitrification as well as organic carbon decomposition. PMID- 24220149 TI - Utilization of sepiolite materials as a bottom liner material in solid waste landfills. AB - Landfill bottom liners are generally constructed with natural clay soils due to their high strength and low hydraulic conductivity characteristics. However, in recent years it is increasingly difficult to find locally available clay soils that satisfy the required engineering properties. Fine grained soils such as sepiolite and zeolite may be used as alternative materials in the constructions of landfill bottom liners. A study was conducted to investigate the feasibility of using natural clay rich in kaolinite, sepiolite, zeolite, and their mixtures as a bottom liner material. Unconfined compression tests, swell tests, hydraulic conductivity tests, batch and column adsorption tests were performed on each type of soil and sepiolite-zeolite mixtures. The results of the current study indicate that sepiolite is the dominant material that affects both the geomechanical and geoenvironmental properties of these alternative liners. An increase in sepiolite content in the sepiolite-zeolite mixtures increased the strength, swelling potential and metal adsorption capacities of the soil mixtures. Moreover, hydraulic conductivity of the mixtures decreased significantly with the addition of sepiolite. The utilization of sepiolite-zeolite materials as a bottom liner material allowed for thinner liners with some reduction in construction costs compared to use of a kaolinite-rich clay. PMID- 24220150 TI - Tar-free fuel gas production from high temperature pyrolysis of sewage sludge. AB - Pyrolysis of sewage sludge was studied in a free-fall reactor at 1000-1400 degrees C. The results showed that the volatile matter in the sludge could be completely released to gaseous product at 1300 degrees C. The high temperature was in favor of H2 and CO in the produced gas. However, the low heating value (LHV) of the gas decreased from 15.68 MJ/Nm(3) to 9.10 MJ/Nm(3) with temperature increasing from 1000 degrees C to 1400 degrees C. The obtained residual solid was characterized by high ash content. The energy balance indicated that the most heating value in the sludge was in the gaseous product. PMID- 24220151 TI - The residual life of bendiocarb on different substrates under laboratory and field conditions in Benin, Western Africa. AB - BACKGROUND: The efficacy of bendiocarb against pyrethroid resistant An. gambiae and the residual life of this insecticide on different substrates were evaluated under laboratory and field conditions. METHODS: Bioassays according to the WHO (World Health Organization) standard protocol were carried out on different substrates impregnated with bendiocarb. Data were analyzed using a binomial regression model with R software. RESULTS: A good efficacy of the bendiocarb against pyrethroid resistant An. gambiae and a high variation of its residual life according to the surfaces treated was observed. The probability that a female mosquito died after exposure to a treated substrate was below 80% after 13 weeks for the teak wood; 7 weeks for the wall made with a mixture of sand and cement and 6 weeks for walls made with red clay and those made with a mixture of the red clay and cement. CONCLUSIONS: Considering the residual life of bendiocarb on walls made with red clay, the main substrates treated during IRS campaigns in rural areas in Benin, more than 2 treatments rounds per year would be necessary to achieve a long term efficacy of IRS using bendiocarb in these areas. Financial and logistical resources required to achieve such levels of coverage need more political will from leaders of African endemic countries. While waiting for innovative malaria control tool, alternative insecticides or combinations of insecticides have to be used for insecticide resistance management in Benin. PMID- 24220152 TI - Glycoprotein import: a common feature of complex plastids? AB - Complex plastids evolved by secondary endosymbiosis and are, in contrast to primary plastids, surrounded by 3 or 4 envelope membranes. Recently, we provided evidence that in diatoms proteins exist that get N-glycosylated during transport across the outermost membrane of the complex plastid. This gives rise to unique questions on the transport mechanisms of these bulky proteins, which get transported across up to 3 further membranes into the plastid stroma. Here we discuss our results in an evolutionary context and speculate about the existence of plastidal glycoproteins in other organisms with complex plastids. PMID- 24220153 TI - Discussion. PMID- 24220154 TI - Endovascular coil embolization of segmental arteries prevents paraplegia after subsequent thoracoabdominal aneurysm repair: an experimental model. AB - OBJECTIVES: To test a strategy for minimizing ischemic spinal cord injury after extensive thoracoabdominal aneurysm (TAAA) repair, we occluded a small number of segmental arteries (SAs) endovascularly 1 week before simulated aneurysm repair in an experimental model. METHODS: Thirty juvenile Yorkshire pigs (25.2 +/- 1.7 kg) were randomized into 3 groups. All SAs, both intercostal and lumbar, were killed by a combination of surgical ligation of the lumbar SAs and occlusion of intercostal SAs with thoracic endovascular stent grafting. Seven to 10 days before this simulated TAAA replacement, SAs in the lower thoracic/upper lumbar region were occluded using embolization coils: 1.5 +/- 0.5 SAs in group 1 (T13/L1), and 4.5 +/- 0.5 SAs in group 2 (T11-L3). No SAs were coiled in the controls. Hind limb function was evaluated blindly from daily videotapes using a modified Tarlov score (0 = paraplegia, 9 = full recovery). After death, each segment of spinal cord was graded histologically using the 9-point Kleinman score (0 = normal, 8 = complete necrosis). RESULTS: Hind limb function remained normal after coil embolization. After simulated TAAA repair, paraplegia occurred in 6 of 10 control pigs, but in only 2 of 10 pigs in group 1; no pigs in group 2 had a spinal cord injury. Tarlov scores were significantly better in group 2 (control vs group 1, P = .06; control vs group 2, P = .0002; group 1 vs group 2, P = .05). A dramatic reduction in histologic damage, most prominently in the coiled region, was seen when SAs were embolized before simulated TAAA repair. CONCLUSIONS: Endovascular coiling of 2 to 4 SAs prevented paraplegia in an experimental model of extensive hybrid TAAA repair, and helped protect the spinal cord from ischemic histopathologic injury. A clinical trial in a selected patient population at high risk for postoperative spinal cord injury may be appropriate. PMID- 24220155 TI - Variant vicilins from a resistant Vigna unguiculata lineage (IT81D-1053) accumulate inside Callosobruchus maculatus larval midgut epithelium. AB - It has been demonstrated that variant vicilins are the main resistance factor of cowpea seeds (Vigna unguiculata) against attack by the cowpea beetle Callosobruchus maculatus. There is evidence that the toxic properties of these storage proteins may be related to their interaction with glycoproteins and other microvillar membrane constituents along the digestive tract of the larvae. New findings have shown that following interaction with the microvilli, the vicilins are absorbed across the intestinal epithelium and thus reach the internal environment of the larvae. In the present paper we studied the insecticidal activity of the variant vicilins purified from a resistant cowpea variety (IT81D 1053). Bioassays showed that the seeds of this genotype affected larval growth, causing developmental retardation and 100% mortality. By feeding C. maculatus larvae on susceptible and IT81D-1053 derived vicilins (FITC labelled or unlabelled), followed by fluorescence and immunogold cytolocalization, we were able to demonstrate that both susceptible and variant forms are internalized in the midgut cells and migrate inside vesicular structures from the apex to the basal portion of the enterocytes. However, when larvae were fed with the labelled vicilins for 24h and then returned to a control diet, the concentration of the variant form remained relatively high, suggesting that variant vicilins are not removed from the cells at the same rate as the non-variant vicilins. We suggest that the toxic effects of variant vicilins on midgut cells involve the binding of these proteins to the cell surface followed by internalization and interference with the normal physiology of the enterocytes, thereby affecting larval development in vivo. PMID- 24220156 TI - Should bowel preparation, antifoaming agents, or prokinetics be used before video capsule endoscopy? A systematic review and meta-analysis. AB - OBJECTIVES: The ideal bowel preparation regime before small bowel video capsule endoscopy (VCE) is not known. We carried out a systematic review and meta analysis to study the effect of purgatives, antifoaming agents, and prokinetics on the outcomes associated with VCE. MATERIALS AND METHODS: We performed literature searches in MEDLINE and Cochrane Library and included randomized controlled trials studying the effect of purgatives, antifoaming agents, and prokinetics in patients undergoing VCE. Our outcomes of interest were visualization quality, diagnostic yield, and completion rate. Meta-analyses were carried out using the RevMan software and heterogeneity was assessed using the I statistic. RESULTS: Fifteen studies fulfilled the inclusion criteria. As compared with no bowel preparation, bowel preparation with polyethylene glycol (PEG) led to adequate visualization in a significantly higher number of patients undergoing VCE [odds ratio (OR) 3.13; 95% confidence interval (CI) 1.70-5.75]. Both PEG and sodium phosphate significantly improved the diagnostic yield (OR 1.68; 95% CI 1.16-2.42 and OR 1.77; 95% CI 1.18-2.64, respectively) but did not affect the completion rate. All studies with simethicone showed significantly improved visualization quality with its use as compared with overnight fasting or purgatives alone. Prokinetics did not significantly improve the completion rate of VCE. CONCLUSION: On the basis of the data available, a combination of PEG and simethicone appears to be the best approach for small bowel preparation before VCE. However, large multicenter randomized-controlled trials are needed to validate this recommendation and to evaluate the ideal dose of PEG and timing of bowel preparation before VCE. Prokinetics administered before VCE do not improve the completion rate and should not be used. PMID- 24220157 TI - Spondyloarthritis: may the force be with you? PMID- 24220158 TI - Contemporary systemic therapy for male breast cancer. AB - BACKGROUND: The use, effectiveness, and tolerability of tamoxifen, aromatase inhibitors, and trastuzumab in early and advanced male breast cancer were examined at a population level. PATIENTS AND METHODS: A total of 158 consecutively referred men with invasive breast cancer diagnosed between 2000 and 2010 were identified. Stage and prognostic factors were compared with a random sample of contemporary female patients. Survival outcomes were compared with a separate female cohort matched 2:1 by prognostic and treatment factors. RESULTS: Men were older (median 69.5 years) than women (median 60 years) and presented with more advanced stage disease. Estrogen receptor was positive in 96% (n = 152) of cases. Tamoxifen was more commonly used than aromatase inhibitors in the curative and metastatic settings. Adherence to adjuvant tamoxifen therapy was generally adequate with estimated actuarial rates of persistence at 1 year and 3.5 years of 89% and 70%, respectively. For the 146 men treated with curative intent, 5-year overall survival, breast cancer-specific survival and progression free survival were 72%, 86%, and 62%, respectively. Outcomes were similar to matched female patients in univariate and multivariate analyses. CONCLUSIONS: In this large population-based study, outcomes appear similar between male and risk matched female patients with breast cancer. Side effect profiles, tolerance, adherence, and outcomes after tamoxifen, aromatase inhibitors, and trastuzumab in men appear comparable with those described in the literature for women. PMID- 24220159 TI - An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. AB - HMGB1 (High-Mobility Group Box-1) is a nuclear protein that acts as an architectural chromatin-binding factor involved in the maintenance of nucleosome structure and regulation of gene transcription. It can be released into the extracellular milieu from immune and non-immune cells in response to various stimuli. Extracellular HMGB1 contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases, including sepsis, rheumatoid arthritis, atherosclerosis, chronic kidney disease, systemic lupus erythematosus (SLE), as well as cancer pathogenesis. Interaction of released HMGB1 with the cell-surface receptor for advanced glycation end products (RAGE) is one of the main signaling pathways triggering these diseases. It has been also demonstrated that the inhibition of the HMGB1-RAGE interaction represents a promising approach for the modulation of the inflammatory and tumor-facilitating activity of HMGB1. In this review we describe various approaches recently proposed in the literature to inhibit HMGB1 and the related inflammatory processes, especially focusing on the block of RAGE-HMGB1 signaling. Several strategies are based on molecules which mainly interact with RAGE as competitive antagonists of HMGB1. As an alternative, encouraging results have been obtained with HMGB1-targeting, leading to the identification of compounds that directly bind to HMGB1, ranging from small natural or synthetic molecules, such as glycyrrhizin and gabexate mesilate, to HMGB1-specific antibodies, peptides, proteins as well as bent DNA-based duplexes. Future perspectives are discussed in the light of the overall body of knowledge acquired by a large number of research groups operating in different but related fields. PMID- 24220160 TI - Activity of xenobiotic-metabolizing enzymes in the liver of rats with multi vitamin deficiency. AB - The purpose of the study was to determine how multi-vitamin deficiency affects xenobiotic-metabolizing enzyme (XME) activities in the rat liver. Vitamin levels and XME activities were studied in the livers of male Wistar rats who were fed for 4 weeks with semi-synthetic diets containing either adequate (100 % of recommended vitamin intake) levels of vitamins (control), or decreased vitamin levels (50 % or 20 % of recommended vitamin intake). The study results have shown that moderate vitamin deficiency (50 %) leads to a decrease of vitamin A levels only, and to a slight increase, as compared with the control, in the following enzyme activities: methoxyresorufin O-dealkylase (MROD) activity of CYP1 A2 - by 34 % (p < 0.05), UDP-glucuronosyl transferase - by 26 % (p < 0.05), and quinone reductase - by 55 % (p < 0.05). Profound vitamin deficiency (20 %) led to a decrease of vitamins A, E, B1, B2, and C, and enzyme activities in the liver: MROD - to 78 % of the control level (p < 0.05), 4-nitrophenol hydroxylase - to 74 % (p < 0.05), heme oxygenase-1 - to 83 % (p < 0.05), and quinone reductase - to 60 % (p < 0.05). At the same time, the UDP-glucuronosyl transferase activity and ethoxyresorufin O-dealkylase activity of CYP1A1, pentoxyresorufin O-dealkylase activity of CYP2B1/2 and 6beta-testosterone hydroxylase, as well as the total activity of glutathione transferase did not differ from the control levels. The study has demonstrated that profound multi-vitamin deficiency is associated with a decrease in the expression of CYP1A2 and CYP3A1 mRNAs to 62 % and 79 %, respectively. These data indicated that a short-term but profound multi-vitamin deficiency in rats leads to a decrease in the activities and expression of the some XME that play an important role in detoxification of xenobiotics and metabolism of drugs and antioxidant protection. PMID- 24220161 TI - The impact of prenatal vitamin A and zinc supplementation on birth size and neonatal survival - a double-blind, randomized controlled trial in a rural area of Indonesia. AB - BACKGROUND: Prenatal supplementation with micronutrients may increase birth weight and thus improve infant health and survival in settings where infants and children are at risk of micronutrient deficiencies. OBJECTIVE: To assess whether vitamin A and/or zinc supplementation given during pregnancy can improve birth weight, birth length, neonatal morbidity, or infant mortality. METHODS: A double blind, randomized controlled trial supplementing women (n = 2173) in Central Java, Indonesia throughout pregnancy with vitamin A, zinc, combined vitamin A+zinc, or placebo. RESULTS: Out of 2173 supplemented pregnant women, 1956 neonates could be evaluated. Overall, zinc supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.8 vs. 48.5 cm, p = 0.04); vitamin A supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.7 vs. 48.2 cm, p = 0.04). These effects remained after adjusting for maternal height, pre-pregnancy weight, and parity. There was no effect of supplementation on birth weight, the proportion of low birth weight, neonatal morbidity, or mortality. CONCLUSIONS: Prenatal zinc or vitamin A supplementation demonstrates a small but significant effect on birth length, but supplementation with zinc, vitamin A or a combination of zinc and vitamin A, have no effect on birth weight, neonatal morbidity, or mortality. PMID- 24220162 TI - The Effects of Yerba Mate (Ilex Paraguariensis) consumption on IL-1, IL-6, TNF alpha and IL-10 production by bone marrow cells in wistar rats fed a high-fat diet. AB - An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba mate (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL 1alpha, IL-6, TNF-alpha, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1alpha, IL-6, and TNF-alpha, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1alpha, IL-6, and TNF-alpha production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1alpha, IL-6, and TNF-alpha production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1alpha, IL-6, and TNF alpha by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS. PMID- 24220163 TI - Omega 3 and omega 6 fatty acids intake and dietary sources in a representative sample of Spanish adults. AB - The present study analyzes the intake of omega 3 (n-3 PUFAs) and omega 6 (n-6 PUFAs) and dietary sources in a representative sample of Spanish adults. For this purpose 418 adults (18 - 60 y), from 15 Spanish provinces were studied. The intake of energy and nutrients [specifically, the n-3 polyunsaturated fatty acids (PUFAs,) alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA); and the n-6 PUFA, linoleic acid (LA)] was determined using a 24-hour recall questionnaire for two days. The Multiple Source Method (MSM) was used to estimate participants? usual fatty acid intake. The total n-3 PUFAs intake was 1.8 +/- 0.60 g/day (ALA: 1.3 +/- 0.32, EPA: 0.16 +/- 0.14, and DHA: 0.33 +/- 0.21 g/day) and n-6 PUFA intake was 11.0 +/- 2.7 g/day (LA: 10.8 +/- 2.7 g/day). A high proportion of participants did not meet their nutrient intake goals for total n-3 PUFAs (84.7 %), ALA (45.0 %), and EPA plus DHA (62.9 %). The main food sources for ALA were oil, dairy products, and meat; for EPA fish; for DHA, fish, eggs, and meat; and for LA, oils, meat, and cereals. Therefore, an increase in the intake of foods rich in n-3 PUFAs or the use of supplements with n-3 PUFAs might help to improve the n-3 PUFA intake. PMID- 24220164 TI - Nutritional supplements usage by Portuguese athletes. AB - In this study, we determined the prevalence of nutritional supplements (NS) usage, the type of supplements used, the reasons for usage, and the source of nutritional advice among Portuguese athletes. Two hundred ninety-two athletes (68 % male, 12 - 37 years old) from 13 national sports federations completed a questionnaire that sought information on socio-demographics, sports data, and NS usage. Most athletes (66 %) consumed NS, with a median consumption of 4 supplements per athlete. The most popular supplements included multivitamins/minerals (67 %), sport drinks (62 %), and magnesium (53 %). Significant differences for the type of NS consumed were found between gender and age groups and the number of weekly training hours. Most athletes used NS to accelerate recovery (63 %), improve sports performance (62 %), and have more energy/reduce fatigue (60 %). Athletes sought advice on supplementation mainly from physicians (56 %) and coaches (46 %). Age and gender were found to influence reasons for use and the source of information. Reasons for NS usage were supported scientifically in some cases (e. g., muscle gain upon protein supplementation), but others did not have a scientific basis (e. g., use of glutamine and magnesium). Given the high percentage of NS users, there is an urgent need to provide athletes with education and access to scientific and unbiased information, so that athletes can make assertive and rational choices about the utilization of these products. PMID- 24220165 TI - Rice fortified with iron given weekly increases hemoglobin levels and reduces anemia in infants: a community intervention trial. AB - More than two billion people suffer from anemia worldwide, and it is estimated that more than 50 % of cases are caused by iron deficiency. In this community intervention trial, we evaluated infants aged 10 to 23 months of age (n = 171) from two public child day-care centers. Intervention lasted 18 weeks. The 50-g individual portion (uncooked) of fortified rice provided 56.4 mg of elemental iron as ferric pyrophosphate. Capillary blood samples to test for anemia were taken at baseline and at endpoint. The objective of this study was to evaluate the impact of rice fortified with iron (Ultrarice(r)) on hemoglobin and anemia prevalence compared with standard household rice. For the fortified rice center, baseline mean hemoglobin was 113.7 +/- 9.2 g/L, and at endpoint 119.5 +/- 7.7 g/L, p < 0.0001; for the standard rice center, baseline mean hemoglobin value was 113.5 +/- 40.7 g/L, and at endpoint 113.6 +/- 21.0, p = 0.99. Anemia prevalence for the fortified rice center was 27.8 % (20/72) at baseline, and 11.1 % (8/72) at endpoint, p = 0.012; for the control center, 47.1 % (33/70) were anemic at baseline, and 37.1 % (26/70) at the end of the study, p = 0.23. The Number Needed to Treat (NNT) was 4. In this intervention, rice fortified with iron given weekly was effective in increasing hemoglobin levels and reducing anemia in infants. PMID- 24220166 TI - Rapid determination of coenzyme Q10 in food supplements using 1H NMR spectroscopy. AB - A methodology utilizing 1H NMR spectroscopy has been developed to measure the concentration of coenzyme Q10 (CoQ10) in dietary supplements. For sample preparation, a very simple dilution with deuterated chloroform and addition of internal standard is sufficient. CoQ10 produces a distinct peak of the CH groups in the isoprene side chain of the molecule in the delta 5.15 - 5.05 ppm range, where it can be distinguished from other matrix compounds. The method was shown to be of adequate sensitivity with a limit of detection (LOD) of 7.8 mg/L, to control the CoQ10 content in the majority of the products. The precision expressed as relative standard deviation was around 5 %; linearity was observed from 14 to 2000 mg/L (R = 0.99). The developed methodology was applied for the analysis of 21 food supplements (capsules, tablets, and liquid products). On the basis of the labeled amounts, only two products contained substantially lower concentrations of CoQ10 (57 % and 51 %). All other concentrations varied between 83 % and 190 % with respect to labeling. The developed NMR method may be used by quality assurance laboratories for routine control of CoQ10 products. PMID- 24220168 TI - Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study. AB - Alzheimer's disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer's disease to be associated with disturbances in glucose metabolism and the subsequent tricarboxylic acid (TCA) cycle-related metabolites like glutamate (Glu), glutamine (Gln), and N-acetylaspartate (NAA). These metabolites have been viewed as biomarkers by (a) assisting early diagnosis of Alzheimer's disease and (b) evaluating the efficacy of a treatment regimen. In this study, 13-month-old triple transgenic mice (a mouse model of Alzheimer's disease (3xTg-AD)) were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C NMR to determine the concentrations of (13)C-labeled isotopomers of Glu, Gln, aspartate (Asp), GABA, myo-inositol, and NAA. Total ((12)C+(13)C) Glu, Gln, and Asp were quantified by high-performance liquid chromatography to calculate enrichment. Furthermore, we examined the effects of lipoic acid in modulating these metabolites, based on its previously established insulin mimetic effects. Total (13)C labeling and percent enrichment decreased by ~50% in the 3xTg-AD mice. This hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer's disease. PMID- 24220169 TI - Sterile inflammation after permanent distal MCA occlusion in hypertensive rats. AB - The pathophysiology of stroke is governed by immune reactions within and remote from the injured brain. Hypertension, a major cause and comorbidity of stroke, entails systemic vascular inflammation and may influence poststroke immune responses. This aspect is, however, underestimated in previous studies. Here we aimed to delineate the sequence of cellular inflammation after stroke in spontaneously hypertensive (SH) rats. Spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion and killed after 1 or 4 days. Immune cells of the peripheral blood and those which have infiltrated the injured brain were identified and quantified by flow cytometry. The spatial distribution of myeloid cells and T lymphocytes, and the infarct volume were assessed by histology. We observed a concerted infiltration of immune cells into the ischemic brain of SH rats. At day 1, primarily neutrophils, monocytes, macrophages, and myeloid dendritic cells entered the brain, whereas the situation at day 4 was dominated by microglia, macrophages, lymphatic dendritic cells, and T cells. Postischemic inflammation did not cause secondary tissue damage during the subacute stage of experimental stroke in SH rats. Considering the intrinsic vascular pathology of SH rats, our study validates this strain for further translational research in poststroke inflammation. PMID- 24220170 TI - In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers. AB - The growth inhibition of human cancer cells via T-type Ca(2+) channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca(2+) channel (Cav3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G1 phase in the cell cycle progression of A2780 and A2780 T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca(2+) channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G1 phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca(2+) channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. PMID- 24220171 TI - Novel glycosylated endomorphin-2 analog produces potent centrally-mediated antinociception in mice after peripheral administration. AB - We report the synthesis and pharmacological characterization of a novel glycosylated analog of a potent and selective endogenous MU-opioid receptor (MOP) agonist, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2), obtained by the introduction in position 3 of the tyrosine residue possessing the glucose moiety attached to the phenolic function via a beta-glycosidic bond. The improved blood-brain barrier permeability and enhanced antinociceptive effect of the novel glycosylated analog suggest that it may be a promising template for design of potent analgesics. Furthermore, the described methodology may be useful for increasing the bioavailability and delivery of opioid peptides to the CNS. PMID- 24220172 TI - Novel tacrine-ebselen hybrids with improved cholinesterase inhibitory, hydrogen peroxide and peroxynitrite scavenging activity. AB - A series of tacrine-ebselen hybrids were synthesised and evaluated as possible multifunctional anti-Alzheimer's disease (AD) agents. Compound 6i, which is tacrine linked with 5,6-dimethoxybenzo[d][1,2]selenazol-3(2H)-one by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitor, with IC50 values of 2.55 and 2.80 nM, respectively. Furthermore, this compound demonstrated similar hydrogen peroxide and peroxynitrite scavenging activity as ebselen by horseradish peroxidase assay and peroxynitrite scavenging activity assay, indicating that this hybrid is a good multifunctional drug candidate for the treatment of AD. PMID- 24220173 TI - Preparation, in vitro evaluation and molecular modelling of pyridinium quinolinium/isoquinolinium non-symmetrical bisquaternary cholinesterase inhibitors. AB - Two series of non-symmetrical bisquaternary pyridinium-quinolinium and pyridinium isoquinolinium compounds were prepared as molecules potentially applicable in myasthenia gravis treatment. Their inhibitory ability towards human recombinant acetylcholinesterase and human plasmatic butyrylcholinesterase was determined and the results were compared to the known effective inhibitors such as ambenonium dichloride, edrophonium bromide and experimental compound BW284C51. Two compounds, 1-(10-(pyridinium-1-yl)decyl)quinolinium dibromide and 1-(12 (pyridinium-1-yl)dodecyl)quinolinium dibromide, showed very promising affinity for acetylcholinesterase with their IC50 values reaching nM inhibition of acetylcholinesterase. These most active compounds also showed satisfactory selectivity towards acetylcholinesterase and they seem to be very promising as leading structures for further modifications and optimization. Two of the most promising compounds were examined in the molecular modelling study in order to find the possible interactions between the ligand and tested enzyme. PMID- 24220174 TI - Deep cognitive imaging systems enable estimation of continental-scale fire incidence from climate data. AB - Unplanned fire is a major control on the nature of terrestrial ecosystems and causes substantial losses of life and property. Given the substantial influence of climatic conditions on fire incidence, climate change is expected to substantially change fire regimes in many parts of the world. We wished to determine whether it was possible to develop a deep neural network process for accurately estimating continental fire incidence from publicly available climate data. We show that deep recurrent Elman neural network was the best performed out of ten artificial neural networks (ANN) based cognitive imaging systems for determining the relationship between fire incidence and climate. In a decennium data experiment using this ANN we show that it is possible to develop highly accurate estimations of fire incidence from monthly climatic data surfaces. Our estimations for the continent of Australia had over 90% global accuracy and a very low level of false negatives. The technique is thus appropriate for use in estimating the spatial consequences of climate scenarios on the monthly incidence of wildfire at the landscape scale. PMID- 24220175 TI - New promising hybrid materials for electromagnetic interference shielding with improved stability and mechanical properties. AB - A novel transparent Co0.2Fe2.8O4@SiO2-polyetheretherketone hybrid material is prepared for electromagnetic interference shielding via in situ sol-gel process. 20% amino-functionalized polyetheretherketone (AFPEEK), containing trifluoromethyl units with excellent solubility is designed and synthesized to improve the stability and mechanical properties of Co0.2Fe2.8O4@SiO2 nanoparticles. The hydrophilic nanoparticles and hydrophobic polymer matrix are covalently connected after the effective interface modification with 3 isocyanatopropyltriethoxysilane. SEM and TEM images demonstrate that the strong interaction between inorganic-organic phases results in great improvement of dispersion and compatibility at even 40 wt% nanoparticles contents. The functional integration of organic polymer and inorganic nanoparticles leads to excellent comprehensive performances such as high transparency, thermal stability and mechanical properties of the hybrid material, as well as the high adhesion with substrate, which benefits its application as coating materials. This high performance material exhibits good superparamagnetic behaviour and microwave electromagnetic properties (RLmax ~ -13 dB), which can be utilized as a promising electromagnetic interference shielding material. PMID- 24220176 TI - [Plasma urea along with every plasma creatinine test?]. AB - The concentration of plasma creatinine and the estimated glomerular filtration rate, calculated from plasma creatinine, age, weight, and gender, are used to assess kidney function. In routine clinical practice the concentration of plasma urea is often determined at the same time as the creatinine concentration. Urea is a waste product of the breakdown of amino acids and is excreted by the kidneys. Thus reduced kidney function results in a rise of blood urea. In addition, the urea concentration is determined by protein supply and catabolism. The sensitivity and specificity of urea in the diagnosis of kidney dysfunction are therefore low. In only a limited number of cases might measuring urea be helpful in determining the cause of reduced kidney function. PMID- 24220177 TI - [IgG4-related disease]. AB - The diagnosis IgG4-related disease (IgG4-RD) is often difficult to make. The clinical spectrum is diverse, with a variety of organ systems that may be affected simultaneously or sequentially. Patients often present with symptoms that mimic a malignant disease, for example, symptoms compatible with a pancreatic tumour. The lack of reliable tests often prolongs the diagnostic process. Limited insight into the causative disease mechanisms has confined the therapeutic options to the empirical use of immunosuppression. During the past year, the first papers on the fundamental aspects of the disease have resulted in the emergence of a new disease model for IgG4-RD. Recently published clinical and experimental findings support the hypothesis that antigenic stimulation plays a pivotal role in the aetiology of IgG4-RD. These new insights may pave the way for more sensitive diagnostic tests and more evidence-based strategies to cope with the many manifestations of IgG4-related disease. PMID- 24220178 TI - [Societal costs of asthma, COPD and respiratory allergy]. AB - OBJECTIVE: To estimate the societal costs of asthma, COPD and respiratory allergy for the year 2007 and future healthcare costs for the period 2007-2032. DESIGN: Descriptive study. METHODS: Representative registries were used to estimate the healthcare costs of asthma, COPD and respiratory allergy for the year 2007. A simulation model for asthma and COPD and a demographic projection for respiratory allergy were used to determine future healthcare costs. Production losses due to sick leave and work incapacity were calculated using the friction-cost method. RESULTS: Total healthcare costs for asthma, COPD and respiratory allergy in 2007 were estimated at 287, 415 and 103 million euros respectively; on average 530, 1400 and 170 euros per patient with asthma, COPD and respiratory allergy. Average costs of sick leave for asthma were on average 1200 euros and for COPD 1900 euros per employee per year. The costs of work incapacity of an employee with COPD were 1200 euros. There is expected to be an increase in the number of patients from 443,000 in 2007 to 567,000 in 2032 for asthma and from 335,000 to 600,000 for COPD. The number of patients with a respiratory allergy are expected to remain approximately stable at 625,000 patients. The healthcare costs for respiratory allergy are expected to rise by 73%, those for asthma to double, and those for COPD to triple. CONCLUSION: Patients with asthma and COPD have high healthcare costs. Sick leave makes up a large part of the costs of asthma and COPD. In addition, the costs of work incapacity for employees with COPD are high. The number of patients with asthma and COPD will rise in the coming decades, as well as the healthcare costs for these diseases. PMID- 24220179 TI - [Hypoglycaemia with low insulin levels: what insulin tests do not measure]. AB - Insulin can be measured by immunochemical methods using polyclonal or monoclonal antibodies. Monoclonal antibodies are specific in the detection of pure human insulin, and may show little to no cross reactivity with pro-insulin or recombinant insulin. Polyclonal antibodies, however, do show such cross reactivity. Most medical laboratories use commercial (monoclonal) methods to measure insulin 75% of which are not capable of detecting pro-insulin or exogenous insulin. This pitfall in diagnostics may lead to prolonged uncertainty for both patient and physician, which we illustrate with two patients. The first patient was a 45-year-old woman with DM type 1 who for years suffered from hypoglycaemic attacks. Factitious hypoglycaemia went undiagnosed because our monoclonal assay did not detect the overdose insulin analogues. The second patient was a 47-year-old woman with recurrent hypoglycaemic attacks. An insulinoma, which produced pro-insulin, was only detected after using polyclonal insulin and specific pro-insulin assays. PMID- 24220180 TI - [Illness, health and sunlight]. AB - New scientific insights show that the influence of sunlight on health is profound. Recent data suggest that our skin is well adapted to the Dutch climate, but changes in the exposure pattern cause a steady increase in skin cancer. These changes mainly consist of a decrease in daily exposure and a shift from a regular to an intermittent exposure. In the Netherlands, probably the best advice is for moderate, frequent exposure to the sun. Evidence is accumulating that frequent exposure to sunlight is a protective factor against colorectal, prostate, and breast cancer and non-Hodgkin lymphoma, multiple sclerosis and metabolic syndrome. The circadian rhythm is affected by light. Too low levels of exposure to light in daytime and too high levels of exposure to light in the evening and at night can weaken and disrupt the circadian rhythm. This disruption most probably is a risk factor for some types of cancer and metabolic syndrome. PMID- 24220181 TI - [A woman with a wound on her hand]. AB - A 37-year-old woman came to the Emergency Room. Since 7 days she had a growing wound of the left hand with a necrotic centre. She had increasing erythema and edema of the left arm, and a fever. PCR-investigation revealed the cow pox virus. Cow pox are rare but self-limiting. PMID- 24220182 TI - [Dynamic compression brace for pectus carinatum]. AB - Pectus carinatum occurs in one of 1500-1700 people and may lead to physical, cosmetic and psychosocial problems. Surgical treatment of pectus carinatum is performed using the 'Ravitch procedure'. An alternative and less invasive treatment consists of external compression with a brace. Results are often disappointing because of skin complications, a low level of comfort of the brace and low compliance. Nowadays a new brace (dynamic compression brace) exists with which the comfort and thus the compliance can be increased by measuring and regulating the pressure of correction during the treatment. This leads to better results and fewer complications. In 80-90% of patients the results are good to excellent and an operation can be avoided. This new brace is therefore a less invasive, cheap and safe alternative to the Ravitch procedure in the treatment of pectus carinatum in children. PMID- 24220183 TI - [Pain during labour: sterile water injections?]. AB - In the spring of 2013, the association of Dutch midwifes announced that midwifes would be offering sterile water injections for women in pain during labour. Shortly afterwards, the Dutch associations of gynaecologists and anaesthesiologists criticized this step, as the evidence for this intervention was considered insufficient. We reviewed the literature by critically appraising two recent systematic reviews. Although the overlap of included randomized trials was considerable, the reviews came to different conclusions regarding the primary outcome of one of the reviews, i.e. the proportion of unplanned caesarean sections. The order of magnitude of the effect estimated was similar, but in only one of the reviews the confidence interval encompassed 'no difference'. This discrepancy between the reviews was caused by a small difference in included trials. The results of planned and ongoing trials may reveal whether sterile water injections deserve a place in guidelines. PMID- 24220184 TI - [Screening for lung cancer using CT: time for implementation?]. AB - Screening for lung cancer with computed tomography (CT) appears to be highly effective. A large randomized trial in the United States reported a 7% reduction in all-cause mortality in patients screened by CT in comparison with those screened by chest radiography. The problem of dealing with the large number of pulmonary nodules and false positive test results could be solved by a protocol from the Dutch-Belgian lung cancer screening trial which proposes a strategy based on nodule volume and volumetry. Additional findings related to chronic obstructive pulmonary disease and cardiovascular disease are common in lung cancer screening and may provide an opportunity to increase screening benefits at minimal cost in the future. As CT is superior to radiography in lung cancer detection, CT seems the preferred imaging modality for case finding. As more trial results have to be awaited and cost-effectiveness and optimal screening strategy remain uncertain, CT lung cancer screening is not yet ready for implementation. PMID- 24220185 TI - Human milk feeding supports adequate growth in infants <= 1250 grams birth weight. AB - BACKGROUND: Despite current nutritional strategies, premature infants remain at high risk for extrauterine growth restriction. The use of an exclusive human milk based diet is associated with decreased incidence of necrotizing enterocolitis (NEC), but concerns exist about infants achieving adequate growth. The objective of this study was to evaluate growth velocities and incidence of extrauterine growth restriction in infants <= 1250 grams (g) birth weight (BW) receiving an exclusive human milk-based diet with early and rapid advancement of fortification using a donor human milk derived fortifier. METHODS: In a single center, prospective observational cohort study, preterm infants weighing <= 1250 g BW were fed an exclusive human milk-based diet until 34 weeks postmenstrual age. Human milk fortification with donor human milk derived fortifier was started at 60 mL/kg/d and advanced to provide 6 to 8 additional kilocalories per ounce (or 0.21 to 0.28 kilocalories per gram). Data for growth were compared to historical growth standards and previous human milk-fed cohorts. RESULTS: We consecutively evaluated 104 infants with mean gestational age of 27.6 +/- 2.0 weeks and BW of 913 +/- 181 g (mean +/- standard deviation). Weight gain was 24.8 +/- 5.4 g/kg/day with length 0.99 +/- 0.23 cm/week and head circumference 0.72 +/- 0.14 cm/week. There were 3 medical NEC cases and 1 surgical NEC case. 22 infants (21%) were small for gestational age at birth. Overall, 45 infants (43%) had extrauterine growth restriction. Weight velocity was affected by day of fortification (p = 0.005) and day of full feeds (p = 0.02). Our cohort had significantly greater growth in weight and length compared to previous entirely human milk-fed cohorts. CONCLUSIONS: A feeding protocol for infants <= 1250 g BW providing an exclusive human milk-based diet with early and rapid advancement of fortification leads to growth meeting targeted standards with a low rate of extrauterine growth restriction. Consistent nutritional policies using this approach may be considered for this population. PMID- 24220186 TI - The UK National Ligament Registry. PMID- 24220187 TI - Fractography and oxidative analysis of gamma inert sterilized posterior stabilized tibial insert post fractures: report of two cases. AB - BACKGROUND: Highly crosslinked ultra-high molecular weight polyethylene (UHMWPE) has shown success in reducing wear in hip arthroplasty but there remains skepticism about its use in Total Knee Replacement (TKR) inserts that are known to experience fatigue loading and higher local cyclic contact stresses. METHODS: Two Legacy Posterior-Stabilized (LPS) Zimmer NexGen tibial implants sterilized by gamma irradiation in an inert environment with posts that fractured in vivo were analyzed. Failure mechanisms were determined using optical and scanning electron microscopy along with oxidative analysis via Fourier Transform Infra-Red (FTIR) spectroscopy. RESULTS: Micrographs of one retrieval revealed fatigue crack initiation on opposite sides of the post and quasi-brittle micromechanisms of crack propagation. FTIR of this retrieval revealed no oxidation. The fracture surface image of the second retrieval indicated a brittle fracture process and FTIR revealed oxidation in the explant. CONCLUSIONS: These two cases suggest that crosslinking of UHMWPE as a manufacturing process or sterilization method in conjunction with designs that incorporate high stress concentrations, such as the tibial post, may reduce material strength. Moreover, free radicals generated from ionizing radiation can render the polymer susceptible to oxidative embrittlement. CLINICAL RELEVANCE: Our findings suggest that tibial post fractures may be the results of in vivo oxidation and low level crosslinking. These and previous reports of fractured crosslinked UHMWPE devices implores caution when used with high stress concentrations, particularly when considering the potential for in vivo oxidation in TKR. PMID- 24220188 TI - Integrated profiling of microRNA expression in membranous nephropathy using high throughput sequencing technology. AB - The present study analyzed microRNA (miRNA) expression profiles in peripheral blood lymphocyte cells (PBLCs) from patients with membranous nephropathy (MN) and normal controls (NC), in an effort to improve the understanding of the pathogenesis of MN. High-throughput sequencing was performed on 30 MN patients and 30 healthy individuals (NC group). Known and novel miRNAs were analyzed and the results were confirmed by quantitative reverse transcription PCR (qRT-PCR). In total, 326 miRNAs showed a significant difference in expression between the MN and NC groups. This included 286 downregulated miRNAs and 40 upregulated miRNAs. In addition, there were 6 novel miRNAs that presented differential levels of expression between the MN and NC groups. The miRNAs were mapped to the genome, using a short oligonucleotide alignment program (SOAP), to analyze their expression and distribution. Twenty-five percent of the unique miRNAs in the MN group and 52.1% in the NC group were mapped to the genome. One hundred and eight mismatches were identified. Seventy-seven mismatches were detected in a higher proportion of the MN samples, compared with the NC samples. Twenty-five mismatches were detected in a higher proportion of the NC samples than the MN samples. Differential miRNA expression was also detected between 10 randomly selected pair groups, as depicted in a cluster analysis diagram. These data indicate that differential miRNA expression may be involved in the pathogenesis of MN. In addition, the discrepancies between the MN and NC groups, in the mismatched miRNAs that were mapped to the genome, strongly suggest that miRNAs play an important role in the pathogenesis of human disorders. miRNAs may provide a potential breakthrough in the research of MN and may provide a novel biomarker for the diagnosis and treatment of the disease. PMID- 24220189 TI - Near full-length genome analysis of HCV genotype 5 strains from South Africa. AB - Hepatitis C virus (HCV) genotype 5 is the predominant genotype in South Africa. However, to date, only 2 full-length genotype 5 genomes have been sequenced and only one is from South Africa. This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support. Bayesian analysis of the E1 region was used to estimate the time of the most recent common ancestor (tMRCA). The tMRCA for HCV genotype 5a was estimated at 114-134 years before the last sampling date. In conclusion, this study provides six near full-length genotype 5 nucleotide sequences for use as references to design efficient vaccines and for the development of new antiviral agents, and provides further insight into the diversity of HCV genotypes circulating in South Africa. PMID- 24220192 TI - Microwave synthesis and adsorption performance of a novel crosslinked starch microsphere. AB - A new crosslinked starch microsphere (CSM) was synthesized in a microwave assisted inversed emulsion system with soluble starch (ST) as a raw material, MBAA as a crosslinker, and K2S2O8-NaHSO3 as an initiator. The synthesized starch microsphere was characterized and examined by scanning electron microscope (SEM), FTIR spectroscopy and adsorption isotherms of N2 at 77K. Adsorption performance was investigated in methyl violet solution. The results showed that the maximum adsorption capacity for MV was 99.3mg/g at 298 K, and the adsorption fitted pseudo-second-order kinetic model well with correlation coefficients greater than 0.99. The isothermal data obeyed the Langmuir model better compared to Freundlich model and Tempkin model, and the adsorption was exothermic and spontaneous. pH variations (2.0-10.0) did not significantly affect the adsorption of MV onto CSM. PMID- 24220190 TI - Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma. AB - Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel hypoxia-activated prodrug, Q6, exhibits potent antiproliferative efficacy under hypoxic conditions and induces caspase-dependent apoptosis in 2 hepatocellular carcinoma (HCC) cell lines, with no obvious toxicity being detected in 2 normal liver cell lines. Treatment with Q6 markedly downregulated HIF1A [hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)] expression and transcription of the downstream target gene, VEGFA (vascular endothelial growth factor A). This dual hypoxia-targeted modulation mechanism leads to high potency in suppressing tumor growth and vascularization in 2 in vivo models. Intriguingly, it is the autophagy-dependent degradation pathway that plays a crucial role in Q6-induced attenuation of HIF1A expression, rather than the proteasome-dependent pathway, which is normally regarded as the predominant mechanism underlying posttranslational regulation of HIF1A. Inhibition of autophagy, either by short interfering RNA (siRNA) or by chemical inhibitors, blocked Q6-induced HIF1A degradation. Autophagic degradation of HIF1A was further confirmed by the observation that HIF1A coimmunoprecipitated with the ubiquitin-binding adaptor protein, SQSTM1, which is degraded through autophagy. Additionally, silencing of SQSTM1 inhibited Q6-induced HIF1A degradation. These findings suggest that the novel hypoxia-targeted agent, Q6, has potential clinical value in the therapy of HCC. Furthermore, the identification of autophagy as a crucial regulator of HIF1A provides new insights into hypoxia-related treatments. PMID- 24220191 TI - Estimating personal exposures from ambient air pollution measures: using meta analysis to assess measurement error. AB - BACKGROUND: Although ambient concentrations of particulate matter <=10 MUm (PM10) are often used as proxies for total personal exposure, correlation (r) between ambient and personal PM10 concentrations varies. Factors underlying this variation and its effect on health outcome-PM exposure relationships remain poorly understood. METHODS: We conducted a random-effects meta-analysis to estimate effects of study, participant, and environmental factors on r; used the estimates to impute personal exposure from ambient PM10 concentrations among 4,012 nonsmoking, participants with diabetes in the Women's Health Initiative clinical trial; and then estimated the associations of ambient and imputed personal PM10 concentrations with electrocardiographic measures, such as heart rate variability. RESULTS: We identified 15 studies (in years 1990-2009) of 342 participants in five countries. The median r was 0.46 (range = 0.13 to 0.72). There was little evidence of funnel plot asymmetry but substantial heterogeneity of r, which increased 0.05 (95% confidence interval = 0.01 to 0.09) per 10 ug/m increase in mean ambient PM10 concentration. Substituting imputed personal exposure for ambient PM10 concentrations shifted mean percent changes in electrocardiographic measures per 10 ug/m increase in exposure away from the null and decreased their precision, for example, -2.0% (-4.6% to 0.7%) versus -7.9% ( 15.9% to 0.9%), for the standard deviation of normal-to-normal RR interval duration. CONCLUSIONS: Analogous distributions and heterogeneity of r in extant meta-analyses of ambient and personal PM2.5 concentrations suggest that observed shifts in mean percent change and decreases in precision may be generalizable across particle size. PMID- 24220193 TI - High photocatalytic activity of immobilized TiO2 nanorods on carbonized cotton fibers. AB - In this study, TiO2 nanorods were successfully immobilized on carbon fibers by a facile pyrolysis of natural cotton in nitrogen atmosphere followed by a one-pot hydrothermal method. Carbonized cotton fibers (CCFs) and TiO2-CCFs composites were characterized using field-emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffractometer (XRD), diffuse reflectance UV-vis spectroscopy (DRS) and photoluminescence (PL) spectroscopy. Results implied that the band gap narrowing of TiO2 was achieved after integration of CCFs. Dye adsorption isotherm indicated that the maximum dye adsorption capacity (qm) of CCFs-1000 (13.4 mg/g) was 2 times higher than that of cotton fibers and qm of TiO2-CCFs-1000 (9.0mg/g) was 6-7 times higher than that of TiO2 nanorods. Photocatalytic activity of TiO2 nanorods prepared with 3 mL Ti(OBu)4 showed the highest photocatalytic activity. TiO2-CCFs-1000 exhibited higher activity than TiO2 immobilized on CCFs-400, CCFs-600 and CCFs-800. Good photostability of TiO2 CCFs-1000 was found for dye degradation under visible light irradiation. The enhancement of photocatalytic dye degradation was due to the high adsorptivity of dye molecules, enhanced light adsorption and effective separation of electron hole pairs. This work provides a low-cost and sustainable approach to immobilize nanostructured TiO2 on carbon fibers for environmental remediation. PMID- 24220194 TI - Ferrous-activated persulfate oxidation of arsenic(III) and diuron in aquatic system. AB - In situ chemical oxidation (ISCO) can be an effective technology for the remediation of soil and groundwater polluted by organic and inorganic contaminants. This study investigated the oxidation of arsenic(III) (As(III)) and diuron using ferrous activated persulfate-based ISCO. The results indicated that Fe(II)/persulfate oxidation could be an effective method to oxidize As(III) and diuron. Effects of pH, S2O8(2-) and Fe(II) amounts on the destruction of As(III) and diuron were examined in batch experiments. Acidic conditions favored the removal of As(III) and diuron. Four chelating agents, citric acid (CA), Na2S2O3, diethylene triamine pentaacetic acid (DTPA) and ethylene diamine tetraacetic acid disodium (EDTA-Na2) were used in attempt to maintain the quantity of ferrous ion in solution. In our experiments, CA and Na2S2O3 were found to be more effective than DTPA and EDTA-Na2. Our results also revealed a widely practical prospect of inorganic chelating agent Na2S2O3. Hydroxyl and sulfate radical were determined to play key roles in the oxidation process by using ethanol and tertiary butanol as molecular probes. Oxidation of As(III) yielded As(V) via the electron-transfer reaction. In the oxidation process of diuron, a stepwise nucleophilic substitution of chlorine by hydroxyl and a stepwise oxidation process of the methyl on the dimethylurea group by hydroxyl and sulfate radical were proposed. PMID- 24220195 TI - Hybrid BiOBr-TiO2 nanocomposites with high visible light photocatalytic activity for water treatment. AB - Novel highly active visible light photocatalysts BiOBr-TiO2 nanocomposites were prepared by a facile one-pot solvothermal approach. Series of characterizations verified that the BiOBr nanoscale crystals are highly dispersed in amorphous TiO2 to form the hybrid mesoporous structure. The material shows excellent photocatalytic performance towards photodegradation of Rhodamine B under visible light irradiation. The content ratio between TiO2 and BiOBr plays a key role in the microstructure of the nanocomposites, so as to result in distinguished photocatalytic activity. The sample with a molar ratio of 10 between TiO2 and BiOBr shows the optimum performance. The high photocatalytic activity of BiOBr TiO2 nanocomposites under visible light could be ascribed to the large surface area, opened mesoporous structure, appropriate band-gap, as well as synergistic effect between TiO2 and BiOBr. Besides, the BiOBr-TiO2 composites render a facile separation due to the three-dimensional superstructure. The BiOBr-TiO2 photocatalyst is very promising for water purification as well as other environmental applications. PMID- 24220196 TI - Understanding effects of water characteristics on natural organic matter treatability by PACl and a novel PACl-chitosan coagulants. AB - In this study, we investigated the relationship between water characteristics and removal of natural organic matter (NOM) using polyaluminium chloride (PACl) and a newly developed coagulant obtained by hybridising PACl with chitosan (PACl chitosan) for two different types of water. Using UV-visible spectroscopy analysis, we showed that PACl-chitosan is more effective than PACl for treating water samples that contain higher levels of activated polyhydroxyaromatic moieties. As a result, a lower level of total trihalomethanes formation potential (THMFP) was detected for synthetic water treated with PACl-chitosan coagulant compared to water treated with PACl only. In contrast, no difference was observed for the total THMFP that were formed following coagulation with either coagulant, for water sample containing the same level of organic carbon concentration, but lower levels of polyhydroxyaromatic moieties. Our work shows how the complex characteristics and interactions of organic matter with coagulant component can affect the outcome of the treatment process, and in this case, enhance the treatment. The use of PACl-chitosan was also shown to produce larger floc for both water samples; this again, can lead to better removal. PMID- 24220197 TI - Effective sulfur and energy recovery from hydrogen sulfide through incorporating an air-cathode fuel cell into chelated-iron process. AB - The chelated-iron process is among the most promising techniques for the hydrogen sulfide (H2S) removal due to its double advantage of waste minimization and resource recovery. However, this technology has encountered the problem of chelate degradation which made it difficult to ensure reliable and economical operation. This work aims to develop a novel fuel-cell-assisted chelated-iron process which employs an air-cathode fuel cell for the catalyst regeneration. By using such a process, sulfur and electricity were effectively recovered from H2S and the problem of chelate degradation was well controlled. Experiment on a synthetic sulfide solution showed the fuel-cell-assisted chelated-iron process could maintain high sulfur recovery efficiencies generally above 90.0%. The EDTA was preferable to NTA as the chelating agent for electricity generation, given the Coulombic efficiencies (CEs) of 17.8 +/- 0.5% to 75.1 +/- 0.5% for the EDTA chelated process versus 9.6 +/- 0.8% to 51.1 +/- 2.7% for the NTA-chelated process in the pH range of 4.0-10.0. The Fe (III)/S(2-) ratio exhibited notable influence on the electricity generation, with the CEs improved by more than 25% as the Fe (III)/S(2-) molar ratio increased from 2.5:1 to 3.5:1. Application of this novel process in treating a H2S-containing biogas stream achieved 99% of H2S removal efficiency, 78% of sulfur recovery efficiency, and 78.6% of energy recovery efficiency, suggesting the fuel-cell-assisted chelated-iron process was effective to remove the H2S from gas streams with favorable sulfur and energy recovery efficiencies. PMID- 24220198 TI - Estrogenic chemical effects are independent from the degree of sex role reversal in pipefish. AB - Endocrine disrupting chemicals (EDCs) have been reported to disturb several ecological relevant endpoints. Surprisingly, EDC-induced effects on fish sexual behaviour have been poorly studied despite the fact that even subtle alterations might contribute to a disruption of sexual interactions, thus negatively impacting reproduction. As the few assessments on sexual behaviour have been conducted in species with orthodox sex roles, it might be argued that sex-role reversed species might provide a potentially complementary system to further explore the effects of EDCs on reproduction. In the present study, two pipefish species with distinct degrees of sex-role reversal were selected to further elucidate the impact of chronic EE2 exposure on sexual behaviour and reproduction related endpoints. The obtained results indicate that, independently of the degree of sex role reversal, courtship behaviour seems to resist oestrogenic chemical exposure. However, exposure to environmentally relevant EE2 levels did induce a complete absence of pregnancies at 18 ng/L. Even though pregnancies were observed at intermediate concentrations, the percentage of non-transferred or misplaced oocytes increased and a dose-dependent decrease of oocyte volume was observed. Imbalances in the oogenesis process, induction of vitellogenin in males and the absence of pregnancies highlight that environmental relevant concentrations of EE2 have the potential to negatively affect pipefish populations, most of them inhabiting coastal areas where oestrogenic contamination is more prevalent. PMID- 24220199 TI - Could microwave induced catalytic oxidation (MICO) process over CoFe2O4 effectively eliminate brilliant green in aqueous solution? AB - In this study, we adopted the chemical co-precipitation (CP) method and sol-gel method followed by calcination at temperatures of 100-900 degrees C for 12h to synthesize CoFe2O4 materials, which were further characterized by TEM, XRD and XPS techniques. The properties of CoFe2O4 materials were evaluated in a microwave (MW) induced catalytic oxidation (MICO) process for the elimination of brilliant green (BG). The results showed that: (1) the removal rates of BG gradually decreased over a series of CoFe2O4 materials prepared by CP method and calcinated with 100-700 degrees C (except 900 degrees C) for 12h within three reuse cycles; for comparison, no removal of BG was obtained over CoFe2O4 synthesized by sol-gel method and CoFe2O4-900 (CP); (2) no hydroxyl radicals were captured with salicylic acid used as molecular probe in the MICO process; (3) MW irradiation enhanced the release of residual NaOH within the microstructure of CoFe2O4 and further discolored BG, because BG is sensitive to pH; (4) granular activated carbon (GAC), an excellent MW-absorbing material possessing higher dielectric loss tangent compared to that of a series of CoFe2O4 materials, could not remove BG in suspensions at a higher efficiency, even if the loading amount was 20 g L( 1). Accordingly, MICO process over CoFe2O4 materials and GAC could not effectively eliminate BG in suspensions. PMID- 24220200 TI - Electrocatalytic degradation of methylene blue on PbO2-ZrO2 nanocomposite electrodes prepared by pulse electrodeposition. AB - PbO2-ZrO2 nanocomposite electrodes (P) were prepared by pulse electrodeposition and used for the electrocatalytic degradation of methylene blue (MB). The SEM and XRD tests show that PbO2-ZrO2 nanocomposite electrodes (P) possess more compact structure and finer grain size than PbO2-ZrO2 nanocomposite electrodes (D) prepared by direct electrodeposition. The electrochemical measurements show that PbO2-ZrO2 nanocomposite electrodes (P) have higher oxygen evolution overpotential and the oxidation regions of MB and water are significantly separated. The experimental parameters on electrocatalytic degradation of MB by PbO2-ZrO2 nanocomposite electrodes (P) were evaluated, such as initial MB concentration, current density, pH value and supporting electrolyte concentration. The results indicate that MB and COD removal efficiency of PbO2-ZrO2 nanocomposite electrodes (P) reach 100% and 72.7%, respectively, after 120 min electrolysis at initial 30 mg L(-1) MB concentration at current density of 50 mA cm(-2) in 0.2 mol L(-1) Na2SO4 supporting electrolyte solution, and the degradation of MB follows pseudo first-order kinetics. Compared with PbO2-ZrO2 nanocomposite electrodes (D), PbO2 ZrO2 nanocomposite electrodes (P) show higher COD removal efficiency and instantaneous current efficiency with MB degradation. The experimental results demonstrate that PbO2-ZrO2 nanocomposite electrodes (P) possesses the excellent electrocatalytic properties and show great potential applications in refractory pollutants. PMID- 24220201 TI - Effect of cadmium ion on biodegradation of decabromodiphenyl ether (BDE-209) by Pseudomonas aeruginosa. AB - The influence of Cd(II) ions on the degradation of decabromodiphenyl ether (BDE 209) by an aerobic degrading strain, Pseudomonas aeruginosa, was investigated. The results demonstrated that the strain P. aeruginosa exhibited a high level of resistance against cadmium toxicity, and Cd(II) ions of different concentrations possessed mixed reactions on BDE-209 bioremoval. The degradation efficiency was stimulated at low concentrations of Cd(II) ions (<= 1 mg L(-1)) but inhibited at higher levels (>= 5 mg L(-1)). Subsequent analyses revealed that the increase of cell hydrophobicity and membrane permeability were two main factors for Cd(II) ions of low concentrations to accelerate BDE-209 degradation. However, inhibition effect by high concentrations of Cd(II) ions was mainly attributed to the negative impact of metals on growth and metabolism of the strain. It was also showed through cellular distribution of BDE-209 that different concentration of Cd(II) ions affected the amount of BDE-209 inside or outside the cell at different incubation time. PMID- 24220202 TI - Combination of two-dimensional correlation spectroscopy and parallel factor analysis to characterize the binding of heavy metals with DOM in lake sediments. AB - Enhanced knowledge on the binding of heavy metal (HM) with dissolved organic matter (DOM) is essential for understanding the toxicity and migration of HMs. In this study, two-dimensional correlation spectroscopy (2D-COS) and parallel factor (PARAFAC) analysis were combined to characterize the metal binding properties of DOMs, which were respectively extracted from macrophyte- and algal-dominant sediments (named MDOM and ADOM) in a eutrophic shallow lake. 2D absorption COS revealed that MDOM exhibited more HM binding sites (193, 195, 196, 199, 201, 203, 205, 207, 208, 212, 217 nm) than ADOM (201, 205 nm). PARAFAC analysis identified one protein- and two humic-like components from all titrated samples, with each component exhibiting different binding behaviors. The modified Stern-Volmer model showed that PARAFAC-derived components in MDOM had higher conditional stability constants (logKM) than in ADOM, suggesting that macrophyte-dominant sediments might play a more important role in the detoxification of HMs. Meanwhile, low binding abilities of Zn(II)-DOM complexes indicated that the toxicity of zinc in eutrophic lakes should not be overlooked. More aromatic functional groups and binding sites were suggested to be responsible for the high binding ability. 2D COS was a better approach than PARAFAC analysis for exploring HM-DOM interaction. PMID- 24220203 TI - Will the revised NICE guidelines fuel population caesarean rates in Britain? PMID- 24220204 TI - Quantification of pelvic soft tissue artifact in multiple static positions. AB - Soft tissue artifact (STA) has been identified as the most critical source of error in clinical gait analysis. Multiple calibration is a technique to reduce the impact of STA on kinematic data, which involves several static calibrations through the range of motion of the joint of interest. This study investigated how skin markers at the pelvis were displaced in relation to anatomical body landmarks in multiple static calibration positions. The magnitude and direction of the pelvic marker displacement was assessed in nine different body positions including 90 degrees and 45 degrees hip flexion, maximum hip extension, and pelvic tilt in 20 healthy young adults. ASIS markers were found to be more susceptible to relative displacement than PSIS markers, with displacement particularly evident in positions where the hip was flexed (up to 17 mm). A strong correlation was found between the hip flexion angle and marker displacement (r(2) = 0.70). While the estimated impact of pelvic STA on gait kinematics was relatively small, the findings suggest that activities with large hip flexion would cause larger STA with a greater impact on pelvic kinematics. The skin surface located over the ASIS differed by a mean of 17 mm between standing and supine positions, which could affect the inter-ASIS distance and the location of hip joint center (HJC) by up to 20mm and 10mm, respectively. PMID- 24220205 TI - Comparison of plantar pressures and contact area between normal and cavus foot. AB - BACKGROUND: In pes cavus, the medial longitudinal arch elevation reduces the contact surface area and consequently increases the corresponding plantar pressure measurements. This poor distribution of loads may produce associated pathology and pain in this or other areas of the body. Normal reference values need to be established in order to determine which patterns are prone to pathology. OBJECTIVES: To compare the plantar pressures and weight-bearing surface in a population with pes cavus to a population with neutral feet. METHOD: The sample comprised 68 adults, 34 with pes cavus and 34 with neutral feet. The Footscan USB Gait Clinical System((r)) was used as a platform to measure the total contact area and plantar pressure under the forefoot, midfoot, hindfoot, each metatarsal head, and the overall metatarsal area. A statistical analysis of the data was performed using Student's t-test for independent samples. RESULTS: The pes cavus subjects showed a significant reduction in their weight-bearing area [neutral feet: 165.04 ( +/- 20.68) cm(2); pes cavus: 118.26 ( +/- 30.31) cm(2); p < 0.001] and significantly increased pressures under all zones of the forefoot except the fifth metatarsal [metatarsal pressure: in neutral feet 503,797 ( +/- 9.32) kPa; in pes cavus 656.12 ( +/- 22.39) kPa; p < 0.001]. CONCLUSIONS: Compared to neutral feet, pes cavus feet show a reduction in total contact surface and the load under the first toe. A significant increase is present in the load under the metatarsal areas, but the relative distribution of this load is similar in both groups. PMID- 24220206 TI - Morphologic and hemodynamic analysis of paraclinoid aneurysms: ruptured versus unruptured. AB - BACKGROUND: In order to determine the risk factors related to aneurysm rupture, we studied the aneurysms at the paraclinoid segment of the internal carotid artery by applying morphologic and hemodynamic numerical analyzes. METHODS: 107 patients with 110 paraclinoid aneurysms (26 ruptured, 84 unruptured) were analyzed using computational fluid dynamics based on patient-specific three dimensional geometrical models. A series of morphologic and hemodynamic parameters were evaluated to find the potential indicators of aneurysm rupture. RESULTS: Aneurysms with an irregular shape accounted for 23.1% of the ruptured group and only 8.3% of the unruptured group. The difference was statistically significant (p=0.042, chi(2) test). Ruptured paraclinoid aneurysms were found to be significantly smaller than unruptured aneurysms (p=0.041), which is different from the results of most previous studies. Energy loss (EL) and inflow concentration showed a level of statistical significance to assess the risk of rupture in paraclinoid aneurysms. By multivariate logistic regression analysis, aneurysm shape (regular or irregular), EL and inflow concentration were retained as independently significant parameters. The odds of rupture were increased by 1.65 times for a 10% increase in EL, by 4.88 times for an aneurysm with an irregular shape and by 2.91 times for an aneurysm with concentrated inflow jet. CONCLUSIONS: Irregular shape, larger EL and concentrated inflow jet were independently associated with the rupture status of paraclinoid aneurysms. These findings need to be further confirmed based on large multicenter and multipopulation data. PMID- 24220207 TI - PharmGKB summary: mycophenolic acid pathway. PMID- 24220208 TI - T cell-depleted splenocytes from mice pre-immunized with neuroantigen in incomplete Freund's adjuvant involved in protection from experimental autoimmune encephalomyelitis. AB - Mice immunized with neuroantigens in incomplete Freund's adjuvant (IFA) are resistant to subsequent induction of experimental autoimmune encephalomyelitis (EAE). The mechanisms involved in this protection are complex. Studies on relevant CD4(+) or CD8(+) T cells, including effective and regulatory T cells, have been performed by others. In this work, the effects of CD4(-)-, CD8(-)- splenocytes on protection from EAE in C57BL/6 mice which were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG)35-55 in IFA were evaluated. We observed that MOG-reactive CD4(+) T cells failed to be activated and proliferate when CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice were regarded as antigen-presenting cells (APC). It was shown that these APC expressed lower levels of major histocompatibility complex class II (MHC-II), CD80, and CD86 than naive cells. In addition, CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice showed significantly higher levels of IL-10 mRNA expression. When the immunized-mice were induced to develop EAE, these cells secreted significantly higher levels of IL-10 and produced lower levels of IL-6, leading to decreased secretion of IL-17 and IFN-gamma from MOG-specific CD4(+) T cells. The transfer of CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice was able to ameliorate the subsequent induction of EAE in recipient mice. Thus, MOG/IFA immunization can modulate CD4(-)-, CD8(-)- splenocytes by reducing the expression of antigen-presenting molecules and altering the levels of secreted cytokines. Our study reveals an additional mechanism involved in the protective effects of MOG/IFA pre-immunization in an EAE model. PMID- 24220209 TI - Electrofluorescence switching from a multilayer thin film by spin-assisted layer by-layer assembly of an anionic fluorescent conjugated polyelectrolyte with poly(diallyldimethylammonium chloride). AB - An electrofluorochromic conjugated polyelectrolyte, PFTSO3Na as a polyanion, was synthesized and used in the fabrication of layer-by-layer (LbL) assembled multilayer film with poly(diallyldimethylammonium chloride) (PDDA) as a polycation. The electrofluorescent device (EFD) fabricated from the multilayer thin film of PFTSO3Na /PDDA emits blue light under UV excitation. The fluorescence intensity can be switched off upon electrochemical oxidation. The electrofluorescent behavior of the EFD is reversible and can be switched between the non-fluorescent (oxidized) state and the fluorescent (neutral) state with a maximum contrast ratio (If/If0) of 5.20. PMID- 24220210 TI - The virtual skeleton database: an open access repository for biomedical research and collaboration. AB - BACKGROUND: Statistical shape models are widely used in biomedical research. They are routinely implemented for automatic image segmentation or object identification in medical images. In these fields, however, the acquisition of the large training datasets, required to develop these models, is usually a time consuming process. Even after this effort, the collections of datasets are often lost or mishandled resulting in replication of work. OBJECTIVE: To solve these problems, the Virtual Skeleton Database (VSD) is proposed as a centralized storage system where the data necessary to build statistical shape models can be stored and shared. METHODS: The VSD provides an online repository system tailored to the needs of the medical research community. The processing of the most common image file types, a statistical shape model framework, and an ontology-based search provide the generic tools to store, exchange, and retrieve digital medical datasets. The hosted data are accessible to the community, and collaborative research catalyzes their productivity. RESULTS: To illustrate the need for an online repository for medical research, three exemplary projects of the VSD are presented: (1) an international collaboration to achieve improvement in cochlear surgery and implant optimization, (2) a population-based analysis of femoral fracture risk between genders, and (3) an online application developed for the evaluation and comparison of the segmentation of brain tumors. CONCLUSIONS: The VSD is a novel system for scientific collaboration for the medical image community with a data-centric concept and semantically driven search option for anatomical structures. The repository has been proven to be a useful tool for collaborative model building, as a resource for biomechanical population studies, or to enhance segmentation algorithms. PMID- 24220212 TI - Assessing DSM-5 section III personality traits and disorders with the MMPI-2-RF. AB - An alternative model for diagnosing personality disorders (PDs) appears in DSM-5 Section III. This model includes a set of dimensional personality traits, which along with impairment in personality functioning can be configured to represent one of six PDs. Although specific assessment instruments for these personality traits have already been developed (e.g., the Personality Inventory for DSM-5 [PID-5]), clinicians will likely continue to use omnibus measures of psychopathology that are familiar to them to inform diagnostic decision making. One such measure, the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF), will likely remain in the test armamentarium of many practitioners and be employed to assess the DSM-5 dimensional traits. In the current investigation, we examined the associations between MMPI-2-RF scale scores and the PID-5 trait scores and DSM-5 Section III PDs in a combined sample of university students (n = 668) from the United States and Canada. Our results indicated that the MMPI-2-RF scale scores mostly converge with PID-5 dimensional traits as well as the Section III PDs in a conceptually expected manner. As such, we conclude that the MMPI-2-RF is a potentially useful instrument in assessing personality psychopathology as conceptualized in DSM-5 Section III. PMID- 24220211 TI - Mutational analysis of the rotavirus NSP4 enterotoxic domain that binds to caveolin-1. AB - BACKGROUND: Rotavirus (RV) nonstructural protein 4 (NSP4) is the first described viral enterotoxin, which induces early secretory diarrhea in neonatal rodents. Our previous data show a direct interaction between RV NSP4 and the structural protein of caveolae, caveolin-1 (cav-1), in yeast and mammalian cells. The binding site of cav-1 mapped to the NSP4 amphipathic helix, and led us to examine which helical face was responsible for the interaction. METHODS: A panel of NSP4 mutants were prepared and tested for binding to cav-1 by yeast two hybrid and direct binding assays. The charged residues of the NSP4 amphipathic helix were changed to alanine (NSP446-175-ala6); and three residues in the hydrophobic face were altered to charged amino acids (NSP4(46-175)-HydroMut). In total, twelve mutants of NSP4 were generated to define the cav-1 binding site. Synthetic peptides corresponding to the hydrophobic and charged faces of NSP4 were examined for structural changes by circular dichroism (CD) and diarrhea induction by a neonatal mouse study. RESULTS: Mutations of the hydrophilic face (NSP4(46-175) Ala6) bound cav-1 akin to wild type NSP4. In contrast, disruption of the hydrophobic face (NSP4(46-175)-HydroMut) failed to bind cav-1. These data suggest NSP4 and cav-1 associate via a hydrophobic interaction. Analyses of mutant synthetic peptides in which the hydrophobic residues in the enterotoxic domain of NSP4 were altered suggested a critical hydrophobic residue. Both NSP4HydroMut112 140, that contains three charged amino acids (aa113, 124, 131) changed from the original hydrophobic residues and NSP4AlaAcidic112-140 that contained three alanine residues substituted for negatively charged (aa114, 125, 132) amino acids failed to induce diarrhea. Whereas peptides NSP4wild type 112-140 and NSP4AlaBasic112-140 that contained three alanine substituted for positively charged (aa115, 119, 133) amino acids, induced diarrhea. CONCLUSIONS: These data show that the cav-1 binding domain is within the hydrophobic face of the NSP4 amphipathic helix. The integrity of the helical structure is important for both cav-1 binding and diarrhea induction implying a connection between NSP4 functional and binding activities. PMID- 24220213 TI - Practice sensitive quality indicators in RAI-MDS 2.0 nursing home data. AB - BACKGROUND: In recent years, improving the quality of care for nursing home residents has generated a considerable amount of attention. In response, quality indicators (QIs), based on available evidence and expert consensus, have been identified within the Resident Assessment Instrument-Minimum Data Set 2.0 (RAI MDS 2.0), and validated as proxy measures for quality of nursing home care. We sought to identify practice sensitive QIs; that is, those QIs believed to be the most sensitive to clinical practice. METHOD: We enlisted two experts to review a list of 35 validated QIs and to select those that they believed to be the most sensitive to practice. We then asked separate groups of practicing physicians, nurses, and policy makers to (1) rank the items on the list for overall "practice sensitivity" and then, (2) to identify the domain to which the QI was most sensitive (nursing care, physician care, or policy maker). RESULTS: After combining results of all three groups, pressure ulcers were identified as the most practice sensitive QI followed by worsening pain, physical restraint use, the use of antipsychotic medications without a diagnosis of psychosis, and indwelling catheters. When stratified by informant group, although the top five QIs stayed the same, the ranking of the 13 QIs differed by group. CONCLUSIONS: In addition to identifying a reduced and manageable set of QIs for regular reporting, we believe that focusing on these 13 practice sensitive QIs provides both the greatest potential for improving resident function and slowing the trajectory of decline that most residents experience. PMID- 24220214 TI - Urinary iodine concentrations of pregnant women in rural Bangladesh: a longitudinal study. AB - Iodine is an essential dietary element required for normal fetal growth and development. We aimed to explore intraindividual and interindividual variations in iodine intake in pregnant women and whether non-dietary factors might influence the intake. Iodine intake was assessed in 271 women, residing in Matlab, rural Bangladesh, by measuring their urinary iodine concentration (UIC) at gestational week (GW) 8, 14, 19, and 30 with inductively coupled plasma mass spectrometry. The women's UIC increased significantly during pregnancy (median 241 (GW8) and 300 MUg/l (GW30)). About 6% of the women had insufficient iodine intake (UIC<150 MUg/l) and 10% had excessive iodine intake (UIC>=500 MUg/l) at all of their four sampling occasions. The women's UIC were dependent on their education, socio-economic status, and BMI, as well as the season of sampling and iodine concentrations in drinking water. Supplementation with a multi micronutrient capsule, including 150 MUg potassium iodine, increased the UIC in women with the lowest UIC (10th percentile) at GW30 but decreased the UIC in women with the highest UIC (90th percentile) at GW30. In conclusion, median UIC throughout pregnancy indicated adequate intake of iodine among pregnant women in Matlab, but, notably, consistently insufficient and excessive intake was also prevalent. PMID- 24220215 TI - Geospatial relationships of air pollution and acute asthma events across the Detroit-Windsor international border: study design and preliminary results. AB - The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study investigated ambient air quality across the international border between Detroit, Michigan, USA and Windsor, Ontario, Canada and its association with acute asthma events in 5- to 89-year-old residents of these cities. NO2, SO2, and volatile organic compounds (VOCs) were measured at 100 sites, and particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) at 50 sites during two 2-week sampling periods in 2008 and 2009. Acute asthma event rates across neighborhoods in each city were calculated using emergency room visits and hospitalizations and standardized to the overall age and gender distribution of the population in the two cities combined. Results demonstrate that intra-urban air quality variations are related to adverse respiratory events in both cities. Annual 2008 asthma rates exhibited statistically significant positive correlations with total VOCs and total benzene, toluene, ethylbenzene and xylene (BTEX) at 5-digit zip code scale spatial resolution in Detroit. In Windsor, NO2, VOCs, and PM10 concentrations correlated positively with 2008 asthma rates at a similar 3-digit postal forward sortation area scale. The study is limited by its coarse temporal resolution (comparing relatively short term air quality measurements to annual asthma health data) and interpretation of findings is complicated by contrasts in population demographics and health-care delivery systems in Detroit and Windsor. PMID- 24220217 TI - Recoil effects of a motional scatterer on single-photon scattering in one dimension. AB - The scattering of a single photon with sufficiently high energy can cause a recoil of a motional scatterer. We study its backaction on the photon's coherent transport in one dimension by modeling the motional scatterer as a two-level system, which is trapped in a harmonic potential. While the reflection spectrum is of a single peak in the Lamb-Dicke limit, multi-peaks due to phonon excitations can be observed in the reflection spectrum as the trap becomes looser or the mass of the two-level system becomes smaller. PMID- 24220219 TI - Fabrication of dense two-dimensional assemblies over vast areas comprising gold(core)-silver(shell) nanoparticles and their surface-enhanced Raman scattering properties. AB - Fabrication of dense two-dimensional assemblies consisting of gold(core) silver(shell) nanoparticles and the resulting peculiar surface-enhanced Raman scattering (SERS) activity are reported. The assemblies were prepared via assembly at air-toluene interfaces by drop-casting toluene solutions containing the nanoparticles protected with octadecylamine molecules onto glass plates. This simple process, which does not require special apparatus or significant fabrication time, leads to uniform assemblies over vast areas (~34 cm(2)). In the SERS measurements, the high spatial reproducibility of the SERS signals from p aminothiophenol adsorbed on the assemblies over vast areas demonstrates that this method is useful for the quantitative investigation of SERS mechanisms. Under 532 nm laser excitation, the difference in the enhancement factors of the SERS signals at the a1 mode between assemblies consisting of gold, silver, and core shell nanoparticles can be explained by the degree of overlap of the excitation wavelength with their plasmon coupling modes. In contrast, under 785 nm excitation, even though the plasmon band of the core-shell nanoparticle assemblies does not significantly overlap with the excitation wavelength as compared with that of gold nanoparticle assemblies, the enhancement factor from the core-shell nanoparticle assemblies was stronger than those from the gold nanoparticle assemblies. Therefore, we have demonstrated that the gold(core) silver(shell) nanoparticle assemblies are excellent SERS active materials, which have strong electromagnetic mechanism (EM) as well as chemical mechanism (CM) effects due to the silver shells. PMID- 24220216 TI - A novel system to generate WTC dust particles for inhalation exposures. AB - First responders (FRs) present at Ground Zero within the critical first 72 h after the World Trade Center (WTC) collapse have progressively exhibited significant respiratory injury. The majority (>96%) of WTC dusts were >10 MUm and no studies have examined potential health effects of this size fraction. This study sought to develop a system to generate and deliver supercoarse (10-53 MUm) WTC particles to a rat model in a manner that mimicked FR exposure scenarios. A modified Fishing Line generator was integrated onto an intratracheal inhalation (ITIH) system that allowed for a bypassing of the nasal passages so as to mimic FR exposures. Dust concentrations were measured gravimetrically; particle size distribution was measured via elutriation. Results indicate that the system could produce dusts with 23 MUm mass median aerodynamic diameter (MMAD) at levels up to >=1200 mg/m(3). To validate system utility, F344 rats were exposed for 2 h to ~100 mg WTC dust/m(3). Exposed rats had significantly increased lung weight and levels of select tracer metals 1 h after exposure. Using this system, it is now possible to conduct relevant inhalation exposures to determine adverse WTC dusts impacts on the respiratory system. Furthermore, this novel integrated Fishing Line-ITIH system could potentially be used in the analyses of a wide spectrum of other dusts/pollutants of sizes previously untested or delivered to the lungs in ways that did not reflect realistic exposure scenarios. PMID- 24220221 TI - Considerations for the design of future clinical trials in metastatic renal cell carcinoma. AB - Metastatic renal cell carcinoma (mRCC) remains incurable in most cases, and there is a need to improve outcomes through clinical research, which will include development of novel molecularly targeted or immunotherapeutic agents. There are also many remaining questions regarding the optimization of currently available regimens, including the utility of dose escalation, the benefit of combination therapy, and the optimal sequences of therapies. Addressing these clinical questions will require careful planning and the inclusion of novel elements in trial designs. Future trials should include molecular phenotyping and selection of patients most likely to benefit from targeted therapies. In this article, we consider lessons learned from previous trials in mRCC and discuss how these lessons might be implemented in the design of future trials that focus on clinically useful questions and provide results that can be readily interpreted. The ultimate aim of the next generation of mRCC trials will be rapid cost effective identification, testing, and approval of agents that can improve prognosis in this challenging disease. PMID- 24220220 TI - Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma. AB - OBJECTIVE: Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. METHODS: Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. RESULTS: In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R(2) = 0.55, Pearson correlation = 0.66) and individual levels (82%, ? = 0.45). Response correlated with OS12 at the individual level less robustly (78%, ? = 0.36), and the trial level association was not statistically significant (R(2) = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, ? = 0.44) appeared stronger than the correlation of response (76%, ? = 0.17) with OS12 in the external validation dataset. CONCLUSIONS: PFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC. PMID- 24220222 TI - A short review on the implications of base excision repair pathway for neurons: relevance to neurodegenerative diseases. AB - Oxidative DNA damage results from the attack by reactive oxygen and nitrogen species (ROS/RNS) on human genome. This includes base modifications such as oxidized bases, abasic (AP) sites, and single-strand breaks (SSBs), all of which are repaired by the base excision repair (BER) pathway, one among the six known repair pathways. BER-pathway in mammalian cells involves several evolutionarily conserved proteins and is also linked to genome replication and transcription. The BER-pathway enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease (APE1), form complexes with downstream repair enzymes via protein-protein and DNA-protein interactions. An emerging concept for BER proteins is their involvement in non-canonical functions associated to RNA metabolism, which is opening new interesting perspectives. Various mechanisms that are underlined in maintaining neuronal cell genome integrity are identified, but are inconclusive in providing protection against oxidative damage in neurodegenerative disorders, main emphasis is given towards the role played by the proteins of BER-pathway that is discussed. In addition, mechanisms of action of BER-pathway in nuclear vs. mitochondria as well as the non-canonical functions are discussed in connection to human neurodegenerative diseases. PMID- 24220223 TI - Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses. AB - The polarization into M1 and M2 macrophages (MPhi) is essential to understand MPhi function. Consequently, the aim of this study was to determine the impact of IFN-gamma (M1), IL-4 (M2) and IFN-beta activation of MPhi on the susceptibility to genotype 1 and 2 porcine reproductive respiratory syndrome (PRRS) virus (PRRSV) strains varying in virulence. To this end, monocyte-derived MPhi were generated by culture during 72h and polarization was induced for another 24h by addition of IFN-gamma, IL-4 or IFN-beta. MPhi were infected with a collection of PRRSV isolates belonging to genotype 1 and genotype 2. Undifferentiated and M2 MPhi were highly susceptible to all PRRSV isolates. In contrast, M1 and IFN-beta activated MPhi were resistant to low pathogenic genotype 1 PRRSV but not or only partially to genotype 2 PRRSV strains. Interestingly, highly virulent PRRSV isolates of both genotypes showed particularly high levels of infection compared with the prototype viruses in both M1 and IFN-beta-treated MPhi (P<0.05). This was seen at the level of nucleocapsid expression, viral titres and virus-induced cell death. In conclusion, by using IFN-gamma and IFN-beta stimulated MPhi it is possible to discriminate between PRRSV varying in genotype and virulence. Genotype 2 PRRSV strains are more efficient at escaping the intrinsic antiviral effects induced by type I and II IFNs. Our in vitro model will help to identify viral genetic elements responsible for virulence, an information important not only to understand PRRS pathogenesis but also for a rational vaccine design. Our results also suggest that monocyte-derived MPhi can be used as a PRRSV infection model instead of alveolar MPhi, avoiding the killing of pigs. PMID- 24220224 TI - Effect of treadmill training on fatigue in multiple sclerosis: a pilot study. AB - People with multiple sclerosis (PwMS) tend to be less physically active than the general population. Limited physical activity increases fatigue, possibly affecting other functions such as balance. Treadmill training is a promising method to ameliorate these symptoms. The aim of this study was to assess the effect of treadmill training on fatigue and balance. Thirty PwMS were recruited; the mean age was 47.6 (SD 9.2). The median EDSS score was 5.5 (range 3-6.5). Individuals were randomized into a control group receiving 12 sessions of conventional therapy and an experimental group receiving conventional therapy including 15 min of treadmill training. Rate of perceived exertion (RPE), heart rate (HR), the Fatigue Severity Scale, and the Berg Balance Scale were assessed before and after rehabilitation. Despite a low HR (107 beats/min), the RPE score was high (15.8) at baseline assessment. In the experimental group, RPE decreased significantly to 12.8 (P=0.04) after training. Treadmill training also had a positive effect on HR, but no changes in the Fatigue Severity Scale and balance were observed. In conclusion, PwMS showed a high level of exertion before treatment. Treadmill training was effective in reducing the level of perceived fatigue, with no impact on balance. PMID- 24220225 TI - Evaluation of the effects of different culture media on the myogenic differentiation potential of adipose tissue- or bone marrow-derived human mesenchymal stem cells. AB - The creation of functional muscles/muscle tissue from human stem cells is a major goal of skeletal muscle tissue engineering. Mesenchymal stem cells (MSCs) from fat/adipose tissue (AT-MSCs), as well as bone marrow (BM-MSCs) have been shown to bear myogenic potential, which makes them candidate stem cells for skeletal muscle tissue engineering applications. The aim of this study was to analyse the myogenic differentiation potential of human AT-MSCs and BM-MSCs cultured in six different cell culture media containing different mixtures of growth factors. The following cell culture media were used in our experiments: mesenchymal stem cell growth medium (MSCGM)TM as growth medium, MSCGM + 5-azacytidine (5-Aza), skeletal muscle myoblast cell growth medium (SkGM)-2 BulletKitTM, and 5, 30 and 50% conditioned cell culture media, i.e., supernatant of human satellite cell cultures after three days in cell culture mixed with MSCGM. Following the incubation of human AT-MSCs or BM-MSCs for 0, 4, 8, 11, 16 or 21 days with each of the cell culture media, cell proliferation was measured using the alamarBlue(r) assay. Myogenic differentiation was evaluated by quantitative gene expression analyses, using quantitative RT-PCR (qRT-PCR) and immunocytochemical staining (ICC), using well-defined skeletal markers, such as desmin (DES), myogenic factor 5 (MYF5), myosin, heavy chain 8, skeletal muscle, perinatal (MYH8), myosin, heavy chain 1, skeletal muscle, adult (MYH1) and skeletal muscle actin-alpha1 (ACTA1). The highest proliferation rates were observed in the AT MSCs and BM-MSCs cultured with SkGM-2 BulletKit medium. The average proliferation rate was higher in the AT-MSCs than in the BM-MSCs, taking all six culture media into account. qRT-PCR revealed the expression levels of the myogenic markers, ACTA1, MYH1 and MYH8, in the AT-MSC cell cultures, but not in the BM-MSC cultures. The muscle-specific intermediate filament, DES, was only detected (by ICC) in the AT-MSCs, but not in the BM-MSCs. The strongest DES expression was observed using the 30% conditioned cell culture medium. The detection of myogenic markers using different cell culture media as stimuli was only achieved in the AT MSCs, but not in the BM-MSCs. The strongest myogenic differentiation, in terms of the markers examined, was induced by the 30% conditioned cell culture medium. PMID- 24220226 TI - Coffee polyphenols exert hypocholesterolemic effects in zebrafish fed a high cholesterol diet. AB - BACKGROUND: Hypercholesterolemia is an important risk factor for the development of coronary artery disease. Some dietary polyphenols, such as coffee polyphenols (CPPs), reduce cholesterol levels. The mechanism of this cholesterol-lowering effect is not fully understood, although 5-CQA, a major component of CPPs, reportedly inhibits cholesterol biosynthesis. Here, we investigated the mechanism of the cholesterol-lowering effect of CPPs on the basis of cholesterol metabolism related gene expression in the liver. We also examined the effects of CPPs on vascular lipid accumulation in zebrafish with high cholesterol diet-induced hypercholesterolemia. METHODS: Over 14 weeks, adult zebrafish were fed a control diet, a high-cholesterol diet, or the latter diet supplemented with CPPs. To measure the extent of vascular lipid accumulation, for 10 days larval zebrafish (which are optically transparent) were fed these same diets with the addition of a fluorescent cholesteryl ester. RESULTS: In adult zebrafish, addition of CPPs to a high-cholesterol diet significantly suppressed the increase in plasma and liver cholesterol levels seen when fish ingested the same diet lacking CPPs. Transcription levels of the liver genes hmgcra (encoding 3-hydroxy-3 methylglutaryl-coenzyme A reductase A, a rate-limiting enzyme in cholesterol biosynthesis) and mtp (encoding microsomal triglyceride transfer protein, a lipid transfer protein required for assembly and secretion of lipoproteins) were significantly lower in fish fed the CPP-containing diet than in fish fed the unsupplemented high-cholesterol diet. In contrast, the expression level of the liver gene cyp7a1a (encoding the cytochrome P450 polypeptide 1a of subfamily A of family 7, a rate-limiting enzyme for bile acid biosynthesis) increased significantly upon consumption of the CPP-containing diet. In larval fish, accumulation of fluorescently labeled cholesterol in the caudal artery was greatly reduced on the CPP-containing diet. CONCLUSIONS: CPP ingestion suppressed cholesterol accumulation in the plasma, liver, and vascular system of zebrafish. Downregulation of cholesterol and lipoprotein synthesis and upregulation of bile acid synthesis in the liver may be the fundamental underlying mechanisms by which CPPs exert their hypocholesterolemic effects. CPP intake may help prevent and manage hypercholesterolemia in humans, and further investigations along these lines using a variety of CPP dose rates are warranted. PMID- 24220227 TI - Autophagy and phagocytosis converge for better vision. AB - The retinal pigment epithelium (RPE) is a single layer of nonregenerating cells essential to homeostasis in the retina and the preservation of vision. While the RPE perform a number of important functions, 2 essential processes are phagocytosis, which removes the most distal tips of the photoreceptors to support disk renewal, and the visual cycle, which maintains the supply of chromophore for regeneration of photo-bleached visual pigments. We recently reported that these processes are linked by a noncanonical form of autophagy termed LC3-associated phagocytosis (LAP) in which components of the autophagy pathway are co-opted by phagocytosis to recover vitamin A in support of optimal vision. Here we summarize these findings. PMID- 24220228 TI - Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated in serial cultures from the respiratory tract of children with cystic fibrosis. AB - BACKGROUND: Little is known about strain relatedness of methicillin-resistant Staphyloccocus aureus (MRSA) isolated at serial time points from the respiratory tract of patients with cystic fibrosis (CF). The objectives are to interrogate the genetic diversity of MRSA recovered in serial cultures from children with CF and to correlate strain relatedness with clinical characteristics. METHODS: We performed a retrospective analysis of children with CF from whom MRSA was isolated from serial respiratory cultures from 2005 to 2011. Within individual patients, relatedness of isolated strains was determined by repetitive-sequence polymerase chain reaction, and the staphylococcal cassette chromosome mec type of each isolate was characterized. Medical records corresponding to the MRSA cultures were reviewed. RESULTS: We identified 54 CF patients with serial MRSA cultures (145 distinct cultures). Over time, 45 (83%) patients maintained the same strain type and 9 (17%) possessed at least 2 distinct strain types. A total of 91 pairs of isolates were analyzed for strain relatedness. Of these, 81 (89%) were identical and 10 (11%) were distinct strain types. About 117 (83%) isolates were staphylococcal cassette chromosome mec type II, 24 (17%) were staphylococcal cassette chromosome mec type IV and 4 were other types not resolvable with our assay. Clinical factors, including time interval and prescription of antibiotics effective against MRSA between positive cultures, did not correlate with acquisition of a distinct MRSA strain by individual patients. CONCLUSIONS: Our data suggest that sustained presence of MRSA in CF patients is most commonly attributable to identical strain types. Acquisition of distinct MRSA strains in the airway is infrequent. PMID- 24220230 TI - Clostridium septicum brain abscesses in a premature neonate. AB - Brain abscesses in neonates are typically caused by Gram-negative organisms. There are no previously described cases caused by Clostridium septicum. We present a case of a premature male infant who developed recurrent episodes of suspected necrotizing enterocolitis followed by brain abscesses, cerebritis and ventriculitis caused by C. septicum. PMID- 24220229 TI - Epidemiology of Bordetella pertussis in San Luis Potosi, Mexico. AB - We analyzed data from 147 patients with suspected pertussis in San Luis Potosi, Mexico. Bordetella pertussis was detected by real-time polymerase chain reaction in 59 (40.1%) cases. The incidence of B. pertussis infection was 2.3 per 100,000 population. There were 6 deaths among the study patients. We conclude that the impact of pertussis in our state is significantly higher than previously estimated. PMID- 24220231 TI - No evidence for replication of a field strain of bluetongue virus serotype 1 in the blood of domestic dogs. AB - The potential role of domestic dogs in the long-distance transmission of bluetongue virus (BTV) is currently unproven. This study set out, through an experimental infection study, to investigate whether domestic dogs mount a viraemia post-infection with a field strain of BTV serotype 1. All six experimentally infected dogs seroconverted within 14 days and viral RNA was detected in the blood of the dogs, albeit at significantly lower levels than that seen in domestic ruminants. There was no clear evidence for viral replication in the dogs as no increase in viral RNA was observed in, and it was not possible isolate virus from, the blood of the dogs. There was however evidence for a persistence of viral RNA in the blood of the dogs, which may be evidence for a low level of replication or could be indicative of persistence of the viral inoculum. PMID- 24220232 TI - Temperature dependence of photoluminescence dynamics of self-assembled monolayers of CdSe quantum dots: the influence of the bound-exciton state. AB - We have investigated the temperature dependence of photoluminescence (PL) dynamics of self-assembled monolayers (SAMs) of CdSe quantum dots (QDs). The PL decay profiles become slower with an increase in temperature up to 160 K, contrary to an ordinary behavior due to thermal quenching. Such anomalous temperature dependence of the PL-decay profile is explained using a four-state model which introduces a bound-exciton state into a conventional three-state model consisting of a ground state and two excited states: a lower-lying dark exciton state and a higher-lying bright-exciton state. Furthermore, it is proposed that the radiative decay time of QDs is strongly influenced by the presence or absence of the bound-exciton state. PMID- 24220233 TI - Patients' reported reasons for non-use of an internet-based patient-provider communication service: qualitative interview study. AB - BACKGROUND: The adoption of Internet-based patient-provider communication services (IPPC) in health care has been slow. Patients want electronic communication, and the quality of health care can be improved by offering such IPPCs. However, the rate of enrollment in such services remains low, and the reasons for this are unclear. Knowledge about the barriers to use is valuable during implementation of IPPCs in the health care services, and it can help timing, targeting, and tailoring IPPCs to different groups of patients. OBJECTIVE: The goal of our study was to investigate patients' views of an IPPC that they could use from home to pose questions to nurses and physicians at their treatment facility, and their reported reasons for non-use of the service. METHODS: This qualitative study was based on individual interviews with 22 patients who signed up for, but did not use, the IPPC. RESULTS: Patients appreciated the availability and the possibility of using the IPPC as needed, even if they did not use it. Their reported reasons for not using the IPPC fell into three main categories: (1) they felt that they did not need the IPPC and had sufficient access to information elsewhere, (2) they preferred other types of communication such as telephone or face-to-face contact, or (3) they were hindered by IPPC attributes such as login problems. CONCLUSIONS: Patients were satisfied with having the opportunity to send messages to health care providers through an IPPC, even if they did not use the service. IPPCs should be offered to the patients at an appropriate time in the illness trajectory, both when they need the service and when they are receptive to information about the service. A live demonstration of the IPPC at the point of enrollment might have increased its use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00971139; http://clinicaltrial.gov/ct2/show/NCT00971139 (Archived by WebCite at http://www.webcitation.org/6KlOiYJrW). PMID- 24220234 TI - High-power broadband organic THz generator. AB - The high-power broadband terahertz (THz) generator is an essential tool for a wide range of THz applications. Here, we present a novel highly efficient electro optic quinolinium single crystal for THz wave generation. For obtaining intense and broadband THz waves by optical-to-THz frequency conversion, a quinolinium crystal was developed to fulfill all the requirements, which are in general extremely difficult to maintain simultaneously in a single medium, such as a large macroscopic electro-optic response and excellent crystal characteristics including a large crystal size with desired facets, good environmental stability, high optical quality, wide transparency range, and controllable crystal thickness. Compared to the benchmark inorganic and organic crystals, the new quinolinium crystal possesses excellent crystal properties and THz generation characteristics with broader THz spectral coverage and higher THz conversion efficiency at the technologically important pump wavelength of 800 nm. Therefore, the quinolinium crystal offers great potential for efficient and gap-free broadband THz wave generation. PMID- 24220235 TI - Cervicogenic pain in Eagle's syndrome. PMID- 24220236 TI - New cyclometallated Ru(II) complex for potential application in photochemotherapy? AB - In an effort to create a molecule that absorbs further into the optimum window for photochemotherapy (PCT), the new cyclometallated complex [Ru(biq)2(phpy)](PF6) (1, biq = 2,2'-biquinoline, phpy(-) = deprotonated 2 phenylpyridine) was synthesized, characterized and compared to the known photoactive complexes [Ru(biq)2(bpy)](PF6)2 (2, bpy = 2,2'-bipyridine) and [Ru(biq)2(phen)](PF6)2 (3, phen = 1,10-phenanthroline), both of which undergo exchange of one biq ligand when irradiated with red light in coordinating solvents. Excited state ligand dissociation in 2 and 3 is believed to be related to the steric hindrance afforded by the presence of two coordinated biq ligands. The ligand exchange quantum yield of 2 is ~2-fold greater than that of 3, which was shown to be cytotoxic when irradiated with visible light. Cyclometallation results in a red shift of the MLCT absorption maximum of ' by ~100 nm relative to those of 2 and 3, but, although 1 exhibits a distorted octahedral geometry, photoinduced ligand exchange does not occur. DFT calculations were used to aid in our understanding of the lack of photochemistry of 1 which is explained by the destabilization of the eg(sigma*) orbitals upon cyclometallation. PMID- 24220237 TI - Symptomatic pericardial cyst in the presence of partial congenital absence of the pericardium. PMID- 24220239 TI - Effects of electrical stimulation of autonomic nerves to the ovary on the ovarian testosterone secretion rate in rats. AB - Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct precursor of estradiol. Here, we examined the effects of electrical stimulation of the SON and the ONP on ovarian testosterone secretion in rats. On the day of estrous, ovarian venous blood samples were collected intermittently from the ovarian vein. The secretion rate of testosterone from the ovary was calculated from the difference in the testosterone concentration between ovarian venous plasma and systemic arterial blood plasma, and the rate of ovarian venous plasma flow. Stimulation of either the SON or ONP reduced the secretion rate of testosterone from the ovary. The reduction of the testosterone secretion rate by SON stimulation was not influenced by an alpha 2-adrenoceptor antagonist (yohimbine), but it was abolished by an alpha 1-adrenoceptor antagonist (prazosin). Our results show that ovarian nerves have an inhibitory role in ovarian testosterone secretion, via activation of alpha 1-adrenoceptors, but not alpha 2-adrenoceptors. This, therefore, indicates that the reduction of estradiol secretion by SON stimulation is independent of the reduction of testosterone secretion. PMID- 24220238 TI - Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction. AB - Myocardial infarction (MI) is associated with remodeling of the heart and neurohumoral control systems. The objective of this study was to define time dependent changes in intrinsic cardiac (IC) neuronal excitability, synaptic efficacy, and neurochemical modulation following MI. MI was produced in guinea pigs by ligation of the coronary artery and associated vein on the dorsal surface of the heart. Animals were recovered for 4, 7, 14, or 50 days. Intracellular voltage recordings were obtained in whole mounts of the cardiac neuronal plexus to determine passive and active neuronal properties of IC neurons. Immunohistochemical analysis demonstrated an immediate and persistent increase in the percentage of IC neurons immunoreactive for neuronal nitric oxide synthase. Examination of individual neuronal properties demonstrated that after hyperpolarizing potentials were significantly decreased in both amplitude and time course of recovery at 7 days post-MI. These parameters returned to control values by 50 days post-MI. Synaptic efficacy, as determined by the stimulation of axonal inputs, was enhanced at 7 days post-MI only. Neuronal excitability in absence of agonist challenge was unchanged following MI. Norepinephrine increased IC excitability to intracellular current injections, a response that was augmented post-MI. Angiotensin II potentiation of norepinephrine and bethanechol induced excitability, evident in controls, was abolished post-MI. This study demonstrates that MI induces both persistent and transient changes in IC neuronal functions immediately following injury. Alterations in the IC neuronal network, which persist for weeks after the initial insult, may lead to alterations in autonomic signaling and cardiac control. PMID- 24220240 TI - 6-C-(E-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1. AB - Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development and also clarify the underlying mechanisms. Data clearly showed that COX-1 was required for maintenance of malignant characteristics of colon cancer cells or tumor promoter-induced transformation of preneoplastic cells. We also successfully applied a ligand-docking computational method to identify a novel selective COX-1 inhibitor, 6-C-(E-phenylethenyl)-naringenin (designated herein as 6CEPN). 6CEPN could bind to COX-1 and specifically inhibited its activity both in vitro and ex vivo. In colorectal cancer cells, it potently suppressed anchorage independent growth by inhibiting COX-1 activity. 6CEPN also effectively suppressed tumor growth in a 28-day colon cancer xenograft model without any obvious systemic toxicity. Taken together, COX-1 plays a critical role in human colorectal carcinogenesis, and this specific COX-1 inhibitor merits further investigation as a potential preventive agent against colorectal cancer. PMID- 24220241 TI - Effects of notch signaling on regulation of myeloid cell differentiation in cancer. AB - Functionally altered myeloid cells play an important role in immune suppression in cancer, in angiogenesis, and in tumor cells' invasion and metastases. Here, we report that inhibition of Notch signaling in hematopoietic progenitor cells (HPC), myeloid-derived suppressor cells (MDSC), and dendritic cells is directly involved in abnormal myeloid cell differentiation in cancer. Inhibition of Notch signaling was caused by the disruption of the interaction between Notch receptor and transcriptional repressor CSL, which is normally required for efficient transcription of target genes. This disruption was the result of serine phosphorylation of Notch. We demonstrated that increased activity of casein kinase 2 (CK2) observed in HPC and in MDSC could be responsible for the phosphorylation of Notch and downregulation of Notch signaling. Inhibition of CK2 by siRNA or by pharmacological inhibitor restored Notch signaling in myeloid cells and substantially improved their differentiation, both in vitro and in vivo. This study demonstrates a novel mechanism regulation of Notch signaling in cancer. This may suggest a new perspective for pharmacological regulation of differentiation of myeloid cells in cancer. PMID- 24220242 TI - Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. AB - Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin binding integrins alpha3beta1 and alpha6beta1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151(free)) correlates clinically with tumor progression and metastasis. Clustering CD151(free) through its integrin-binding domain promotes accumulation in areas of cell-cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151(free) clustering is a strong regulator of motility even in the absence of alpha3 expression but requires PKCalpha, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151(free) in prostate cancer correlates with poor patient outcome. When CD151(free) is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151(free) as an independent predictor of survival. Moreover, the detection of CD151(free) can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151(free) with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression. PMID- 24220244 TI - Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. AB - Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by an imbalance in oxygen supply and demand because of a poorly organized vasculature, is often a prominent feature in solid tumors. However, to what extent tumor hypoxia regulates the TAM phenotype in vivo is unknown. Here, we show that the myeloid infiltrate in mouse lung carcinoma tumors encompasses two morphologically distinct CD11b(hi)F4/80(hi)Ly6C(lo) TAM subsets, designated as MHC-II(lo) and MHC-II(hi) TAM, both of which were derived from tumor-infiltrating Ly6C(hi) monocytes. MHC-II(lo) TAM express higher levels of prototypical M2 markers and reside in more hypoxic regions. Consequently, MHC II(lo) TAM contain higher mRNA levels for hypoxia-regulated genes than their MHC II(hi) counterparts. To assess the in vivo role of hypoxia on these TAM features, cancer cells were inoculated in prolyl hydroxylase domain 2 (PHD2)-haplodeficient mice, resulting in better-oxygenated tumors. Interestingly, reduced tumor hypoxia did not alter the relative abundance of TAM subsets nor their M2 marker expression, but specifically lowered hypoxia-sensitive gene expression and angiogenic activity in the MHC-II(lo) TAM subset. The same observation in PHD2(+/+) -> PHD2(+/-) bone marrow chimeras also suggests organization of a better-oxygenized microenvironment. Together, our results show that hypoxia is not a major driver of TAM subset differentiation, but rather specifically fine tunes the phenotype of M2-like MHC-II(lo) TAM. PMID- 24220243 TI - Blocking eIF5A modification in cervical cancer cells alters the expression of cancer-related genes and suppresses cell proliferation. AB - Cancer etiology is influenced by alterations in protein synthesis that are not fully understood. In this study, we took a novel approach to investigate the role of the eukaryotic translation initiation factor eIF5A in human cervical cancers, where it is widely overexpressed. eIF5A contains the distinctive amino acid hypusine, which is formed by a posttranslational modification event requiring deoxyhypusine hydroxylase (DOHH), an enzyme that can be inhibited by the drugs ciclopirox and deferiprone. We found that proliferation of cervical cancer cells can be blocked by DOHH inhibition with either of these pharmacologic agents, as well as by RNA interference-mediated silencing of eIF5A, DOHH, or another enzyme in the hypusine pathway. Proteomic and RNA analyses in HeLa cervical cancer cells identified two groups of proteins in addition to eIF5A that were coordinately affected by ciclopirox and deferiprone. Group 1 proteins (Hsp27, NM23, and DJ-1) were downregulated at the translational level, whereas group 2 proteins (TrpRS and PRDX2) were upregulated at the mRNA level. Further investigations confirmed that eIF5A and DOHH are required for Hsp27 expression in cervical cancer cells and for regulation of its key target IkappaB and hence NF-kappaB. Our results argue that mature eIF5A controls a translational network of cancer-driving genes, termed the eIF5A regulon, at the levels of mRNA abundance and translation. In coordinating cell proliferation, the eIF5A regulon can be modulated by drugs such as ciclopirox or deferiprone, which might be repositioned to control cancer cell growth. PMID- 24220247 TI - Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain. AB - The role of serine/threonine protein phosphatase 5 (PP5) in the development of obesity and insulin resistance associated with high-fat diet-feeding (HFD) was examined using PP5-deficient mice (Ppp5c(-/-)). Despite similar caloric intake, Ppp5c(-/-) mice on HFD gained markedly less weight and did not accumulate visceral fat compared to wild-type littermates (Ppp5c(+/+)). On a control diet, Ppp5c(-/-) mice had markedly improved glucose control compared to Ppp5c(+/+) mice, an effect diminished by HFD. However, even after 10 weeks of HFD glucose control in Ppp5c(-/-) mice was similar to that observed in Ppp5c(+/+) mice on the control diet. Thus, PP5 deficiency confers protection against HFD-induced weight gain in mice. PMID- 24220249 TI - Calculation of the performance of magnetic lenses with limited machining precision. AB - To meet a required STEM resolution, the mechanical precision of the pole pieces of a magnetic lens needs to be determined. A tolerancing plugin in the EOD software is used to determine a configuration which both meets the optical specifications and is cost effective under the constraints of current manufacturing technologies together with a suitable combination of correction elements. PMID- 24220248 TI - I think I can't: drink refusal self-efficacy as a mediator of the relationship between self-reported drinking identity and alcohol use. AB - This study examined the relationship between self-reported drinking identity (SRDI), defined as how closely individuals believe drinking is a crucial aspect of their identity (Conner, Warren, Close, & Sparks, 1999), and alcohol use by considering drink-refusal self-efficacy (DRSE) as a potential mediator. Based on previous findings, we expected that SRDI would be negatively associated with DRSE and positively associated with drinking, and that DRSE would be negatively linked with drinking. Further, we expected that DRSE would mediate the association between SRDI and drinking. Participants included 1069 undergraduate students (M age=22.93years, SD=6.29, 76.25% female) from a large southern university who completed computer-based study materials. Gender was associated with SRDI, each of the DRSE subscales, and drinking, indicating that males report greater SRDI, lower DRSE, and increased alcohol consumption. Consistent with expectations, SRDI was negatively linked with DRSE and positively linked with drinking. DRSE subscales were negatively associated with drinking. Further, four measurement models for latent variables were tested for SRDI and each of the three DRSE subscales. Results showed that the emotional relief and social subscales of DRSE mediated the association between SRDI and drinking, however this mediating relationship did not emerge for the opportunistic subscale. Implications of these results are discussed. PMID- 24220251 TI - Quantifying vascular heterogeneity using microbubble disruption-replenishment kinetics in patients with renal cell cancer. AB - PURPOSE: The purposes of this study were to establish the physiological interpretation of the shape parameter of the dynamic contrast-enhanced ultrasound (DCE-US) lognormal perfusion model and to evaluate the clinical significance of the parameter in a sample of patients undergoing antiangiogenic therapy for metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: The physiological interpretation of the lognormal shape parameter was explored using computer simulations of disruption-replenishment in fractal models of the microcirculation generated by a piecewise iterative algorithm in MATLAB. Architectural variety was accomplished by introducing random perturbations to the diameter, length, and branching angles to the growing vascular tree. The shape parameter was extracted from the time-intensity curves and compared with the transit time distributions calculated directly from the simulations. Dynamic contrast-enhanced ultrasound data were obtained from 31 consenting patients with mRCC being treated with antiangiogenic therapy. Lognormal parameters related to the blood volume, mean flow speed, and vascular morphology/heterogeneity extracted before, during, and after therapy were correlated with progression-free survival (PFS). Cox proportional hazard ratios were calculated alongside receiver operator characteristics for different combinations of the vascular parameters to determine their ability to distinguish patients who would progress early (less than the median PFS) versus late (greater than the median PFS). RESULTS: The lognormal shape parameter correlated strongly to the width of the transit time distribution calculated directly from the simulations, and by extension, to the morphology/heterogeneity of the microvascular network (Spearman r = 0.80, P < 0.001, n = 28). Shorter time to progression was predicted by higher baseline heterogeneity (P = 0.003) and a reduction in tumor blood volume less than 43% (P = 0.002) after 2 weeks of treatment. Combining baseline parameters with changes that occur shortly after starting treatment increased the sensitivity and specificity of DCE-US to identify which patients would progress/resist therapy early versus late compared with when the vascular parameters were considered in isolation. CONCLUSIONS: The DCE-US shape parameter from the lognormal perfusion model is representative of microvascular morphology/heterogeneity and may be used to noninvasively characterize the vascular architecture of cancer lesions. A more abnormal flow distribution at baseline predicts for poorer outcome for patients treated with antiangiogenic therapy for metastatic renal cell cancer. Combining pretreatment and on-treatment measurements of vascularity can improve the performance of DCE-US to predict which patients will progress earlier versus later when on antiangiogenic therapy for mRCC. PMID- 24220250 TI - Internet search patterns of human immunodeficiency virus and the digital divide in the Russian Federation: infoveillance study. AB - BACKGROUND: Human immunodeficiency virus (HIV) is a serious health problem in the Russian Federation. However, the true scale of HIV in Russia has long been the subject of considerable debate. Using digital surveillance to monitor diseases has become increasingly popular in high income countries. But Internet users may not be representative of overall populations, and the characteristics of the Internet-using population cannot be directly ascertained from search pattern data. This exploratory infoveillance study examined if Internet search patterns can be used for disease surveillance in a large middle-income country with a dispersed population. OBJECTIVE: This study had two main objectives: (1) to validate Internet search patterns against national HIV prevalence data, and (2) to investigate the relationship between search patterns and the determinants of Internet access. METHODS: We first assessed whether online surveillance is a valid and reliable method for monitoring HIV in the Russian Federation. Yandex and Google both provided tools to study search patterns in the Russian Federation. We evaluated the relationship between both Yandex and Google aggregated search patterns and HIV prevalence in 2011 at national and regional tiers. Second, we analyzed the determinants of Internet access to determine the extent to which they explained regional variations in searches for the Russian terms for "HIV" and "AIDS". We sought to extend understanding of the characteristics of Internet searching populations by data matching the determinants of Internet access (age, education, income, broadband access price, and urbanization ratios) and searches for the term "HIV" using principal component analysis (PCA). RESULTS: We found generally strong correlations between HIV prevalence and searches for the terms "HIV" and "AIDS". National correlations for Yandex searches for "HIV" were very strongly correlated with HIV prevalence (Spearman rank-order coefficient [rs]=.881, P <= .001) and strongly correlated for "AIDS" (rs = .714, P <= .001). The strength of correlations varied across Russian regions. National correlations in Google for the term "HIV" (rs = .672, P = .004) and "AIDS" (rs = .584, P <= .001) were weaker than for Yandex. Second, we examined the relationship between the determinants of Internet access and search patterns for the term "HIV" across Russia using PCA. At the national level, we found Principal Component 1 loadings, including age (-0.56), HIV search (-0.533), and education (-0.479) contributed 32% of the variance. Principal Component 2 contributed 22% of national variance (income, -0.652 and broadband price, 0.460). CONCLUSIONS: This study contributes to the methodological literature on search patterns in public health. Based on our preliminary research, we suggest that PCA may be used to evaluate the relationship between the determinants of Internet access and searches for health problems beyond high-income countries. We believe it is in middle-income countries that search methods can make the greatest contribution to public health. PMID- 24220252 TI - Seven-tesla magnetic resonance imaging in Wilson disease using quantitative susceptibility mapping for measurement of copper accumulation. AB - OBJECTIVES: In Wilson disease (WD), the copper content of cerebral tissue is increased, particularly in the basal ganglia. This study investigated whether a change in magnetic susceptibility can be detected using quantitative susceptibility mapping of the brain in patients with WD compared with healthy controls. MATERIALS AND METHODS: Eleven patients with WD (6 with the neurological form, 5 with the hepatic form) and 10 age-matched healthy controls who gave informed consent were examined at 7 T in a whole-body scanner (MAGNETOM; Siemens Medical Solutions, Erlangen, Germany) using a 24-channel phased array coil (Nova Medical). For imaging, a 3-dimensional spoiled gradient multiecho sequence (repetition time, 40 milliseconds; echo time, 9.76/19.19/28.62 milliseconds; bandwidth, 150 hertz per pixel; voxel size, 0.6 * 0.6 * 0.8 mm) was used. The susceptibility of selected regions (substantia nigra, red nucleus, pallidum, putamen, caudate nucleus) was analyzed in susceptibility maps. RESULTS: The patients with WD showed significantly increased susceptibility (P value, 0.001 0.05) in all analyzed regions compared with healthy controls. This was evident not only in patients with a neurological syndrome but also, with lower values, in patients with isolated hepatic manifestations. The distribution patterns of copper accumulation were different between the patients with neurological and non neurological manifestations of the disease. CONCLUSIONS: In neurologically symptomatic and asymptomatic patients with WD, we found increased magnetic susceptibility in the brain tissue using quantitative susceptibility mapping. PMID- 24220253 TI - Value of 3-T multiparametric magnetic resonance imaging and magnetic resonance guided biopsy for early risk restratification in active surveillance of low-risk prostate cancer: a prospective multicenter cohort study. AB - OBJECTIVES: The objective of this study was to evaluate the role of 3-T multiparametric magnetic resonance imaging (MP-MRI) and magnetic resonance-guided biopsy (MRGB) in early risk restratification of patients on active surveillance at 3 and 12 months of follow-up. MATERIALS AND METHODS: Within 4 hospitals participating in a large active surveillance trial, a side study was initiated. Pelvic magnetic resonance imaging, prostate MP-MRI, and MRGB were performed at 3 and 12 months (latter prostate MP-MRI and MRGB only) after prostate cancer diagnosis in 1 of the 4 participating hospitals. Cancer-suspicious regions (CSRs) were defined on prostate MP-MRI using Prostate Imaging Reporting And Data System (PI-RADS) scores.Risk restratification criteria for active surveillance discontinuance were (1) histopathologically proven magnetic resonance imaging suspicion of node/bone metastases and/or (2) a Gleason growth pattern (GGP) 4 and/or 5 and/or cancer multifocality (>=3 foci) in MRGB specimens of a CSR on MP MRI. RESULTS: From 2009 to 2012, a total of 64 of 82 patients were consecutively and prospectively included and underwent MP-MRI and a subsequent MRGB. At 3 and 12 months of follow-up, 14% (9/64) and 10% (3/30) of the patients were risk restratified on the basis of MP-MRI and MRGB. An overall CSR PI-RADS score of 1 or 2 had a negative predictive value of 84% (38/45) for detection of any prostate cancer and 100% (45/45) for detection of a GGP 4 or 5 containing cancer upon MRGB, respectively. A CSR PI-RADS score of 4 or higher had a sensitivity of 92% (11/12) for detection of a GGP 4 or 5 containing cancer upon MRGB. CONCLUSIONS: Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance. PMID- 24220254 TI - Bone marrow edema pattern identification in patients with lytic bone lesions using digital subtraction angiography-like bone subtraction on large-area detector computed tomography. AB - OBJECTIVE: The objective of this study was to evaluate the performance of digital subtraction angiography (DSA)-like bone subtraction with 2 different registration methods for the identification of bone marrow edema pattern (BMEP) in patients with lytic bone lesions, using magnetic resonance imaging as the criterion standard. MATERIALS AND METHODS: Fifty-five patients with a lytic bone lesion were included in this prospective study with approval from the ethics committee. All patients underwent magnetic resonance imaging and low-dose computed tomographic (CT) perfusion after signing an informed consent. Two CT volumes were used for bone subtraction, which was performed with 2 different algorithms (rigid and nonrigid). Enhancement at the nonlytic bone marrow was considered as a sign of BMEP. Two readers evaluated the images blindly. The presence of BMEP on bone subtracted CT images was evaluated subjectively and quantitatively. Image quality was assessed. Magnetic resonance imaging was used as the criterion standard. RESULTS: Using a rigid registration method, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT with DSA like bone subtraction BMEP was 77%, 100%, 100%, 68%, and 85%, respectively. The interobserver agreement was good (kappa, 0.782). Image quality was better using a nonrigid registration. With this algorithm, artifacts interfered with image interpretation in only 5% of cases. However, there was a noticeable drop in sensitivity and negative predictive value when a nonrigid algorithm was used: 56% and 52%, respectively. The interobserver agreement was average with a nonrigid subtraction algorithm. CONCLUSIONS: Computed tomography with DSA-like bone subtraction is sensitive and highly specific for the identification of BMEP associated with lytic bone lesions. Rigid registering should be preferred, but nonrigid algorithms can be used as a second option when artifacts interfere with image interpretation. PMID- 24220255 TI - Three milieux for interstellar chemistry: gas, dust, and ice. AB - The interdisciplinary science of astrochemistry is 45 years of age, if we pinpoint its origin to have occurred when the first polyatomic molecules were detected in the interstellar gas. Since that time, the field has grown remarkably from an esoteric area of research to one that unites scientists around the globe. Almost 200 different molecules have been detected in the gas-phase of interstellar clouds, mainly by rotational spectroscopy, while dust particles and their icy mantles in colder regions can be probed by vibrational spectroscopy. Astrochemistry is exciting to scientists in a number of different fields. Astronomers are interested in molecular spectra from the heavens because such spectra are excellent probes of the physical conditions where molecules exist, while chemists are interested in the exotic molecules, their spectra, and the unusual chemical processes that produce and destroy them under conditions often very different from those on our home planet. Chemical simulations involving thousands of reactions are now used to calculate concentrations and spectra of interstellar molecules as functions of time. Even biologists share an interest in the subject, because the interstellar clouds of gas and dust, portions of which collapse to form stars and planetary systems, contain organic molecules that may become part of the initial inventory of new planets and may indeed be the precursors of life. An irresistible subject to its practitioners, astrochemistry is proving to be exciting to a much wider audience. In this perspective article, the field is first introduced, and the emphasis is then placed on the three environments in which chemistry occurs in the interstellar medium: the gas phase, the surfaces of bare dust particles, and the ice mantles that cover bare grains in cold dense interstellar clouds. What we do know and what we do not know is distinguished. The status of chemical simulations for a variety of interstellar sources having to do with stellar and planetary evolution is surveyed. An optimistic view of the future of astrochemistry ends the article. PMID- 24220256 TI - Fluorescein fundus angiography with smartphone. PMID- 24220257 TI - Choroidal thickness in age-related macular degeneration. AB - PURPOSE: To examine choroidal thickness in age-related macular degeneration (AMD). METHODS: The hospital-based case series study included patients with nonexudative or exudative AMD as study group, and the control group consisted of subjects with a normal fundus. Choroidal thickness was measured by enhanced depth imaging of spectral domain optical coherence tomography. RESULTS: The study group (126 patients; 204 eyes) included a nonexudative subgroup (n = 50 eyes) and an exudative subgroup (n = 154 eyes), differentiated into eyes with mostly retinal pigment epithelium detachment (n = 35), mostly retinal edema (n = 36), and a subretinal fibrotic scar (n = 83). For 29 patients with unilateral AMD, contralateral normal eyes were compared with affected eyes. The control group consisted of 189 patients (228 eyes). Comparing choroidal thickness between the affected eyes and contralateral unaffected eyes in patients with unilateral AMD revealed no statistically significant differences (all P > 0.20). After adjusting for age and refractive error, subfoveal choroidal thickness was not significantly (all P > 0.10) related with AMD neither as a whole nor with the nonexudative or exudative AMD subgroup nor with the single exudative AMD subtypes (except for the subretinal fibrotic scar subgroup; P = 0.03). Correspondingly, choroidal thickness at a horizontal distance of 1000 MUm from the fovea was not significantly (all P >= 0.30) associated with any subgroup of AMD. In binary regression analysis, the presence of AMD or of its subtypes (except for subretinal fibrotic scar type) was not significantly (all P >= 0.20) associated with subfoveal or parafoveal choroidal thickness after adjustment for age and refractive error. After matching for age, refractive error, and axial length, study group and control group did not differ significantly (all P >= 0.25) in foveal or parafoveal choroidal thickness measurements. CONCLUSION: After adjusting for age and refractive error, AMD, neither in its nonexudative form nor exudative form, was significantly associated with a marked thinning or thickening of the choroid in the foveal and parafoveal region. PMID- 24220258 TI - Diagnostic and therapeutic challenges. PMID- 24220259 TI - Less strained and more efficient GaN light-emitting diodes with embedded silica hollow nanospheres. AB - Light-emitting diodes (LEDs) become an attractive alternative to conventional light sources due to high efficiency and long lifetime. However, different material properties between GaN and sapphire cause several problems such as high defect density in GaN, serious wafer bowing, particularly in large-area wafers, and poor light extraction of GaN-based LEDs. Here, we suggest a new growth strategy for high efficiency LEDs by incorporating silica hollow nanospheres (S HNS). In this strategy, S-HNSs were introduced as a monolayer on a sapphire substrate and the subsequent growth of GaN by metalorganic chemical vapor deposition results in improved crystal quality due to nano-scale lateral epitaxial overgrowth. Moreover, well-defined voids embedded at the GaN/sapphire interface help scatter lights effectively for improved light extraction, and reduce wafer bowing due to partial alleviation of compressive stress in GaN. The incorporation of S-HNS into LEDs is thus quite advantageous in achieving high efficiency LEDs for solid-state lighting. PMID- 24220260 TI - PCDD/F and dioxin-like PCB concentrations during municipal solid waste biomethanation and subsequent composting. AB - PCDD/F and dioxin-like PCB concentrations were compared in different samples of a municipal solid waste (MSW) treatment plant: the initial MSW fraction that enters the biomethanation from the digester, the semi-solid digestate obtained after biomethanation of MSW, and the solids after composting the digestate since the final product is destined for land application and special attention must be paid to these compounds for environmental considerations. The initial MSW sample showed low concentrations of PCDD/Fs, although in the biomethanation output sample the concentration was more than ten times higher. The difference was even more significant for PCBs. In compost samples concentrations for both PCDD/Fs and PCBs were in the same range as in biomethanation or lower. Nevertheless, concentrations found for all samples were low and these treatments do not pose a major problem for the environment in the working conditions used. PMID- 24220261 TI - Removal of steroid estrogens from waste activated sludge using Fenton oxidation: influencing factors and degradation intermediates. AB - The presence of endocrine disrupting compounds (EDCs) in waste activated sludge (WAS) is raising concerns about their influence on animals and the overall food cycle. Traditional sludge stabilization processes cannot remove EDCs effectively. The main objective of this work was to study the removal of four estrogens (estrone (E1), 17beta-estradiol (E2), estriol (E3), and 17alpha-ethinylestradiol (EE2)) in waste activated sludge treated with Fenton oxidation. The effects of H2O2 dosage, initial pH, reaction time, and Fe(II) to H2O2 molar ratio were investigated. Base on both the removal of estrogens and the solubilization of WAS, the proper reaction conditions were recommended as follows: H2O2 dosage=15.62 mmol g(-1), initial pH=3, reaction time=60 min, Fe(II) to H2O2 molar ratio=0.167. Under these conditions, the removal efficiencies of E1, E2, EE2, and E3 were 70%, 90%, 84% and 98%, respectively; compared with non-Fenton treatment, a 24-fold increase in STOC was achieved, and the extent of solubilization of TSS and VSS was close to 13 and 20%, respectively. The degradation intermediates were detected using GC/MS. Results showed that the phenol structures of targets were mostly oxidized to cyclohexenone moieties and quinone-like structures, which indicated that estrogenic activity was weakened. Pregn-4-ene-3,20-dione and pregn 4-en-20-yn-3-one were observed for the first time. Fenton oxidation was shown to offer a promising alternative method of removing EDCs from sludge in pretreatment applications. PMID- 24220262 TI - Target and screening analysis of 940 micro-pollutants in sediments in Tokyo Bay, Japan. AB - Urban societies are using an increasingly diverse array of chemicals, many of which ultimately end up accumulating in urban harbors, where they can act as contaminants alone or as part of a mixture. In attempt to grasp a more complete picture of anthropogenic chemicals in an urban harbor, we analyzed 940 organic chemicals in sediments in Tokyo Bay, one of the most densely populated and modernized areas in the world. For the chemical analysis, we used targeted analytical methods using a GC-MS-MS and a GC-MS-SIM, and a screening analysis using an automated identification and quantification system with a GC-MS database. We detected 195 organic chemicals in the sediments; the sum of concentrations of compounds detected varied from 6095 to 39140MUgkg(-1)dry wt. Since their concentrations increased with proximity to the innermost part of the bay, their sources seem to be mainly sewage treatment plants (STPs) and rivers flowing to this area. Additional confirmation comes from the nature of the identified pollutants, which are characteristic of chemicals used in households as well as fecal matter, business activities and urban run-off. From these results, it was confirmed that sediments in Tokyo Bay are still polluted with a wide range of chemicals, particularly domestic chemicals, despite nearly 100% of wastewater from household and business activities being treated by STPs. PMID- 24220263 TI - The ER-Golgi intermediate compartment feeds the phagophore membrane. AB - A long-standing quest in the autophagy field is to define the membrane origin of the autophagosome. We have established a cell-free assay based on LC3 lipidation that recapitulates multiple regulatory hallmarks of early autophagosome biogenesis. Using a systematic membrane fractionation approach, we have identified the ER-Golgi intermediate compartment (ERGIC) as the most efficient membrane substrate for LC3 lipidation. Further studies indicate that the ERGIC plays an essential role to trigger LC3 lipidation and autophagosome biogenesis by recruiting the key early autophagic factor ATG14. PMID- 24220264 TI - Factors that affect substance users' suicidal behavior: a view from the Addiction Severity Index in Korea. AB - BACKGROUND: In South Korea, it has not been easy to negotiate studies that target drug users who are being punished by law, and accordingly, no study on suicidal ideation among substance users has been accomplished yet. In this study, the factors that affect substance users' suicidal ideation were confirmed. METHODS: It was based on the data collected from 'The 2009 Study on Substance-Dependent Individuals in Korea' , which was conducted by The Catholic University of Korea in 2010 as a project sponsored by the Ministry of Health and Welfare of Korea. This study targeted 523 former hospital inpatients, prison inmates, and persons under protective supervision who had used substances such as psychotropic drugs, marijuana, and narcotic agents, and were in the recovery stage at various treatment/rehabilitation centers. Student's t and chi-square tests were used, and multivariate analysis was performed to examine the strength of the relationships between suicide ideation and various factors. RESULTS: According to this study, 41% of these substance users planned suicide with suicidal ideation. Suicidal ideation was confirmed as associated with an unsatisfactory domestic environment, insufficient and unsatisfactory spare time experiences with others, emotional abuse, severe depression, and trouble with controlling violent behavior. Of the substance users who had planned to commit suicide, 56% attempted suicide. Their suicide attempts were shown to have been associated with insufficient protective supervision and the experiences of physical abuse, trouble with controlling violent behavior, and doctors' prescriptions due to psychological or emotional problems. CONCLUSION: Based on this analysis of the factors that affect suicidal behavior, preventive measures and strategies for substance user were suggested in this study. PMID- 24220265 TI - Knockdown of Livin inhibits growth and invasion of gastric cancer cells through blockade of the MAPK pathway in vitro and in vivo. AB - Livin, a novel member of the human inhibitors of apoptosis protein family, has been shown to be critical for tumor progression and poor prognosis for several types of malignancies. However, limited reports exist regarding the biological functions of Livin in human gastric cancer (GC). The present study investigated the clinical significance of Livin and caspase-3 (CAS-3) in human GC using immunohistochemistry assay, and explore the potential using RNA interference to knockdown Livin expression, including the subsequent effects on tumor growth and invasion in GC cells in vitro and in vivo. Our results showed that the rate of positive expression of Livin was significantly higher in GC tissues compared to that in adjacent non-cancer tissues (ANCT) (64.1 vs. 30.8%, P<0.001), while CAS-3 was lower in GC tissues than in ANCT (33.3 vs. 66.7%, P=0.001). Livin expression was positively correlated with tumor differentiation and lymph node metastases (P=0.009; P=0.007), while CAS-3 was negatively correlated with them (P=0.036; P=0.002) in patients with GC. Furthermore, knockdown of Livin inhibited cell proliferative activities and invasive potential, and induced cell in situ apoptosis in GC cells, accompanied with decreased expression of p38 MAPK, VEGF and MMP-2 and increased expression of CAS-3. In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with Lv-shLivin was significantly smaller compared to those of the PBS group (P<0.01). Taken together, our findings indicate that the expression of Livin is increased in human GC and correlates with tumor differentiation and lymph node metastases, while knockdown of Livin inhibits cell growth and invasion through blockade of the MAPK pathway in GC cells, suggesting that Livin may be a potential therapeutic target for the treatment of GC. PMID- 24220266 TI - The value of tear osmolarity as a metric in evaluating the response to dry eye therapy in the clinic and in clinical trials. PMID- 24220267 TI - Serum biomarker signature identifies patients with B-cell non-Hodgkin lymphoma associated with cryoglobulinemia vasculitis in chronic HCV infection. AB - BACKGROUND: Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). We hypothesized that combination of serum biomarkers could be used to identify B-NHL in HCV patients. METHODS: We measured in 155 HCV infected patients, with and without MC and/or B-NHL, serum levels of eight markers previously described to be increased in patients with B-NHL, i.e. sCD22, sCD27, sIL-2Ralpha, sCD137, free light chains of Ig (ratio kappa/lambda), heavy chains of Ig (ratio IgMkappa/IgMlambda), gammaglobulins and C4. We used a multiparametric analysis to determine a signature that identifies patients with overt B-NHL. RESULTS: Serum levels were significantly different between patients without MC, patients with asymptomatic MC, patients with MC vasculitis and those with MC vasculitis and B NHL for all biomarkers except for sCD137. Using multiparametric analysis, we identified a signature involving sCD27, sIL-2Ralpha, gammaglobulins and C4 levels associated with the presence of overt B-NHL in HCV-infected patients. This signature had a sensitivity of 100%, a specificity of 90%, and positive and negative predictive values of 97 and 100%, respectively for discriminating patients with overt B-NHL and those without B-NHL. CONCLUSION: Our data indicate that serum biomarker signature allows identifying HCV-infected patients presenting with overt B-NHL. PMID- 24220268 TI - Automated antinuclear immunofluorescence antibody screening: a comparative study of six computer-aided diagnostic systems. AB - BACKGROUND: Indirect immunofluorescence (IIF) plays an important role in immunological assays for detecting and measuring autoantibodies. However, the method is burdened by some unfavorable features: the need for expert morphologists, the subjectivity of interpretation, and a low degree of standardization and automation. Following the recent statement by the American College of Rheumatology that the IIF technique should be considered as the standard screening method for the detection of anti-nuclear antibodies (ANA), the biomedical industry has developed technological solutions which might significantly improve automation of the procedure, not only in the preparation of substrates and slides, but also in microscope reading. METHODS: We collected 104 ANA-positive sera from patients with a confirmed clinical diagnosis of autoimmune disease and 40 ANA-negative sera from healthy blood donors. One aliquot of each serum, without information about pattern and titer, was sent to six laboratories of our group, where the sera were tested with the IIF manual method provided by each of the six manufacturers of automatic systems. Assignment of result (pos/neg), of pattern and titer was made by consensus at a meeting attended by all members of the research team. Result was assigned if consensus for pos/neg was reached by at least four of six certifiers, while for the pattern and for the titer, the value observed with higher frequency (mode) was adopted. Seventeen ANA positive sera and six ANA-negative sera were excluded. Therefore, the study with the following automatic instrumentation was conducted on 92 ANA-positive sera and on 34 ANA-negative sera: Aklides, EUROPattern, G-Sight (I-Sight-IFA), Helios, Image Navigator, and Nova View. Analytical imprecision was measured in five aliquots of the same serum, randomly added to the sample series. RESULTS: Overall sensitivity of the six automated systems was 96.7% and overall specificity was 89.2%. Most false negatives were recorded for cytoplasmic patterns, whereas among nuclear patterns those with a low level of fluorescence (i.e., multiple nuclear dots, midbody, nuclear rim) were sometimes missed. The intensity values of the light signal of various instruments showed a good correlation with the titer obtained by manual reading (Spearman's rho between 0.672 and 0.839; P<0.0001 for all the systems). Imprecision ranged from 1.99% to 25.2% and, for all the systems, it was lower than that obtained by the manual IIF test (39.1%). The accuracy of pattern recognition, which is for now restricted to the most typical patterns (homogeneous, speckled, nucleolar, centromere, multiple nuclear dots and cytoplasmic) was limited, ranging from 52% to 79%. CONCLUSIONS: This study, which is the first to compare the diagnostic accuracy of six systems for automated ANA IIF reading on the same series of sera, showed that all systems are able to perform very well the task for which they were created. Indeed, cumulative automatic discrimination between positive and negative samples had 95% accuracy. All the manufacturers are actively continuing the development of new and more sophisticated software for a better definition in automatic recognition of patterns and light signal conversion in end-point titer. In the future, this may avert the need for serum dilution for titration, which will be a great advantage in economic terms and time-saving. PMID- 24220269 TI - Rule-based exposure assessment versus case-by-case expert assessment using the same information in a community-based study. AB - BACKGROUND: Retrospective exposure assessment in community-based studies is largely reliant on questionnaire information. Expert assessment is often used to assess lifetime occupational exposures, but these assessments generally lack transparency and are very time-consuming. We explored the agreement between a rule-based assessment approach and case-by-case expert assessment of occupational exposures in a community-based study. METHODS: We used data from a case-control study of childhood acute lymphoblastic leukaemia in which parental occupational exposures were originally assigned by expert assessment. Key questions were identified from the completed parent questionnaires and, on the basis of these, rules were written to assign exposure levels to diesel exhaust, pesticides and solvents. We estimated exposure prevalence separately for fathers and mothers, and used kappa statistics to assess the agreement between the two exposure assessment methods. RESULTS: Exposures were assigned to 5829 jobs among 1079 men and 6189 jobs among 1234 women. For both sexes, agreement was good for the two assessment methods of exposure to diesel exhaust at a job level (kappa=0.70 for men and kappa=0.71 for women) and at a person level (kappa=0.74 and kappa=0.75). The agreement was good to excellent for pesticide exposure among men (kappa=0.74 for jobs and kappa=0.84 at a person level) and women (kappa=0.68 and kappa=0.71 at a job and person level, respectively). Moderate to good agreement was observed for assessment of solvent exposure, which was better for women than men. CONCLUSIONS: The rule-based assessment approach appeared to be an efficient alternative for assigning occupational exposures in a community-based study for a selection of occupational exposures. PMID- 24220270 TI - Pesticides and respiratory health: where do we go from here? PMID- 24220271 TI - Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia. AB - Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML. PMID- 24220272 TI - Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. AB - High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0-12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P<0.05). The status of 14 genes combined with conventional factors revealed a novel prognostic model ('Model-1') separating patients into four risk groups ('low', 'intermediate', 'high', 'very high risk') with 3-year survival of 95.2, 69.3, 32.8, and 5.3% (P<0.001). Subsequently, a 'gene-only model' ('Model-2') was constructed based on 14 genes also yielding four significant risk groups (P<0.001). Both models were reproducible in the validation cohort (n=175 patients; P<0.001 each). Thus, large-scale genetic and molecular profiling of multiple target genes is invaluable for subclassification and prognostication in MDS patients. PMID- 24220273 TI - The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. AB - Ten-Eleven Translocation-2 (TET2) inactivation through loss-of-function mutation, deletion and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutation is a common event in myeloid and lymphoid malignancies. TET2 gene mutations similar to those observed in myeloid and lymphoid malignancies also accumulate with age in otherwise healthy subjects with clonal hematopoiesis. TET2 is one of the three proteins of the TET (Ten-Eleven Translocation) family, which are evolutionarily conserved dioxygenases that catalyze the conversion of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC) and promote DNA demethylation. TET dioxygenases require 2-oxoglutarate, oxygen and Fe(II) for their activity, which is enhanced in the presence of ascorbic acid. TET2 is the most expressed TET gene in the hematopoietic tissue, especially in hematopoietic stem cells. In addition to their hydroxylase activity, TET proteins recruit the O-linked beta-D-N acetylglucosamine (O-GlcNAc) transferase (OGT) enzyme to chromatin, which promotes post-transcriptional modifications of histones and facilitates gene expression. The TET2 level is regulated by interaction with IDAX, originating from TET2 gene fission during evolution, and by the microRNA miR-22. TET2 has pleiotropic roles during hematopoiesis, including stem-cell self-renewal, lineage commitment and terminal differentiation of monocytes. Analysis of Tet2 knockout mice, which are viable and fertile, demonstrated that Tet2 functions as a tumor suppressor whose haploinsufficiency initiates myeloid and lymphoid transformations. This review summarizes the recently identified TET2 physiological and pathological functions and discusses how this knowledge influences our therapeutic approaches in hematological malignancies and possibly other tumor types. PMID- 24220275 TI - Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. AB - Prior studies have shown that myeloma patients exhibiting either genetically defined high-risk disease or plasma cell leukemia have a poor outcome with a median overall survival (OS) of <=3 years. Results of IFM 2005-01 and 02 suggest that relatively limited bortezomib-containing induction regimens did not produce a major survival benefit among these patients. However, results of recent studies suggest that combination therapy may benefit these patients when given early and again later in the treatment. We evaluated a combination maintenance/consolidation regimen (RVD) following autologous stem cell transplant (ASCT) for high-risk patients to evaluate the impact of this approach on outcome. Following initiation of RVD maintenance, 51% of patients achieved stringent complete response (sCR), with 96% achieving at least VGPR as best response. Median progression free survival (PFS) for all patients is 32 months with a 3 year OS of 93%. The regimen was well tolerated with no grade 3/4 neuropathy. Early ASCT followed by RVD maintenance is a promising strategy for high-risk myeloma patients and delivered excellent response rates, and promising PFS and OS. PMID- 24220276 TI - [Long-term outcome in context of intra uterine growth restriction and/or small for gestational age newborns]. AB - OBJECTIVE: To evaluate long-term outcome after history of intra-uterine growth restriction (IUGR) and/or birth small for gestational age (SGA). METHODS: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations. RESULTS: Neurodevelopmental evaluation at 2 years is lower in those infants, born premature or not. SGA is associated with a high risk of minor cognitive deficiencies, hyperactivity or attention deficit disorders at 5 years or scholar difficulties at 8 years. Those infants are at high risk of metabolic syndrome in adulthood. Most of them will catch up at 6 months for weight and 12 months for height. Even if IUGR is associated with high risk of bronchodysplasia, up to this day, the review of literature did not permit to evaluate respiratory outcome. Adults born SGA have good quality of live and normal professional insertion. One cohort study and more and more animal studies suggest potential trans generational effects. CONCLUSION: Infants born SGA and/or with history of IUGR are at high risk of minor cognitive deficiencies and scholar difficulties. They are also at high risk of metabolic syndrome in adulthood. However, prematurity seems to have a higher effect than IUGR and/or SGA on long term outcomes. PMID- 24220274 TI - Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. AB - We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade >=3 neutropenia was observed in 61.7% of patients; however, grade >=3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features. PMID- 24220277 TI - Internet-based cognitive behavior therapy for procrastination: study protocol for a randomized controlled trial. AB - BACKGROUND: Procrastination, to voluntarily delay an intended course of action despite expecting to be worse-off for the delay, is a persistent behavior pattern that can cause major psychological suffering. Approximately half of the student population and 15%-20% of the adult population are presumed having substantial difficulties due to chronic and recurrent procrastination in their everyday life. However, preconceptions and a lack of knowledge restrict the availability of adequate care. Cognitive behavior therapy (CBT) is often considered treatment of choice, although no clinical trials have previously been carried out. OBJECTIVE: The aim of this study will be to test the effects of CBT for procrastination, and to investigate whether it can be delivered via the Internet. METHODS: Participants will be recruited through advertisements in newspapers, other media, and the Internet. Only people residing in Sweden with access to the Internet and suffering from procrastination will be included in the study. A randomized controlled trial with a sample size of 150 participants divided into three groups will be utilized. The treatment group will consist of 50 participants receiving a 10-week CBT intervention with weekly therapist contact. A second treatment group with 50 participants receiving the same treatment, but without therapist contact, will also be employed. The intervention being used for the current study is derived from a self-help book for procrastination written by one of the authors (AR). It includes several CBT techniques commonly used for the treatment of procrastination (eg, behavioral activation, behavioral experiments, stimulus control, and psychoeducation on motivation and different work methods). A control group consisting of 50 participants on a wait-list control will be used to evaluate the effects of the CBT intervention. For ethical reasons, the participants in the control group will gain access to the same intervention following the 10-week treatment period, albeit without therapist contact. RESULTS: The current study is believed to result in three important findings. First, a CBT intervention is assumed to be beneficial for people suffering from problems caused by procrastination. Second, the degree of therapist contact will have a positive effect on treatment outcome as procrastination can be partially explained as a self-regulatory failure. Third, an Internet based CBT intervention is presumed to be an effective way to administer treatment for procrastination, which is considered highly important, as the availability of adequate care is limited. The current study is therefore believed to render significant knowledge on the treatment of procrastination, as well as providing support for the use of Internet based CBT for difficulties due to delayed tasks and commitments. CONCLUSIONS: To our knowledge, the current study is the first clinical trial to examine the effects of CBT for procrastination, and is assumed to render significant knowledge on the treatment of procrastination, as well as investigating whether it can be delivered via the Internet. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01842945; http://clinicaltrials.gov/show/NCT01842945 (Archived by WebCite at http://www.webcitation.org/6KSmaXewC). PMID- 24220278 TI - Sulfur-doped graphene as a potential alternative metal-free electrocatalyst and Pt-catalyst supporting material for oxygen reduction reaction. AB - In this study, sulfur-doped graphene (S-graphene) was synthesized by thermal treatment of exfoliated graphene under CS2 gas flow. Its electrocatalytic activity as a metal-free catalyst was evaluated and compared with other doped graphenes and commercial platinum nanoparticles loaded on carbon black (Pt/C) catalysts for oxygen reduction reaction (ORR) in fuel cell cathodes. The resultant S-graphene was shown to act as a viable catalyst for ORR and its limiting current density and durability were improved compared to those of the commercial Pt/C catalyst. The current density at -1.0 V for the commercial Pt/C catalyst, pristine graphene, nitrogen-doped graphene (N-graphene) and S-graphene was 4.7, 0.15, 6.26 and 6.99 mA cm(-2), respectively. The durability of S graphene (70.3%) was much better compared to commercial Pt/C (37.2%) and N graphene (67.9%). When S-graphene was used as a supporting material for Pt nanoparticles, its catalytic performance was significantly higher than other Pt catalysts supported on different doped graphenes. Here, we demonstrate that S graphene can be used as a novel graphene-based efficient metal-free ORR catalyst in fuel cells. PMID- 24220279 TI - Carbon nanotubes in medicine & biology - therapy and diagnostics. PMID- 24220280 TI - Frequency of aortic dilation in Noonan syndrome. AB - Noonan syndrome (NS) is a genetic disorder caused by mutations altering proteins relevant to RAS/mitogen-activated protein kinase signal transduction. Cardiac involvement is common, most prevalently pulmonary valve stenosis and hypertrophic cardiomyopathy. Because abnormal mitogen-activated protein kinase signaling contributes to the aortopathy in Marfan syndrome and with rare reports of aortic aneurysm in NS, we undertook a retrospective study of ascending aortic anatomy in 37 patients with NS and without confounding medical conditions. Age ranged from 0.6 to 32 years. Based on the most recent echocardiogram, the aortic annulus and root were dilated in the cohort (mean z scores of 1.14 and 0.98, respectively, p <0.005) but the sinotubular junction and ascending aorta were not (mean z scores of 0.05 and 0.19, respectively). The aortic root was aneurysmal (>2 z scores) in 8 subjects (21.6%). PTPN11 mutations were present in 14 subjects, whose aortic status was similar to the cohort overall. Comparison of age and z scores revealed a modest tendency for the aortic annulus and root to dilate over time. Among 13 subjects with multiple imaging studies over an average of 6.8 years, the average z score increased to 0.78 and 0.39 for the aortic annulus and root, respectively. Multivariate analysis revealed that age accounted for 7.0% and 11.0% of the variance in the aortic annular and root diameters, respectively. In conclusion, we found that aortic annular dilation and aortic root aneurysm are prevalent in NS, often presenting during childhood and progressing over time. Further study is needed to identify potential risks associated with these abnormalities. PMID- 24220281 TI - Commercial versus PARTNER study experience with the transfemoral Edwards SAPIEN valve for inoperable patients with severe aortic stenosis. AB - In patients with aortic stenosis who cannot have surgery, transcatheter aortic valve replacement using the Edwards SAPIEN valve has been shown to improve survival rate and is approved for commercial use in the United States. This study aims to assess the clinical profile, procedural characteristics, and in-hospital complications in patients treated with a commercial SAPIEN valve outside the clinical trial context. We retrospectively analyzed 69 consecutive patients who underwent transcatheter aortic valve replacement with a commercial SAPIEN valve compared with 55 Placement of AoRTic traNscathetER valves (PARTNER) trial patients from cohort B enrolled in the same institution by the same Heart Team. Compared with the commercial group, patients in the PARTNER cohort B had higher mean Society of Thoracic Surgeons score (10 +/- 5 vs 9 +/- 4, p = 0.04) and a lower rate of peripheral arterial disease (19% vs 44%, p = 0.004). Most patients in the commercial group had the procedure under conscious sedation (83% vs 66%, p = 0.03). Planned surgical cut down for vascular access was rare in the commercial group (1.4% vs 46%, p <0.001). The overall rates of major vascular complications, life-threatening or major bleeding, and blood transfusions were lower in commercial group (7.2% vs 27%, p = 0.003; 2.9% vs 16%, p = 0.01; and 28% vs 60%, p <0.001, respectively). In-hospital all-cause mortality (5.8% vs 9.1%, p = 0.51) and stroke rates (7.2% vs 14.5%, p = 0.19) were not statistically different between groups. The median length of hospitalization (p <0.001) and postprocedural length of stay (p = 0.01) was shorter in the commercial group. In conclusion, transfemoral commercial use of the Edwards SAPIEN valve for inoperable patients shows similar in-hospital mortality and stroke rates compared with PARTNER cohort B. The refinements in the procedure such as more conscious sedation, experience of the operators, and careful vascular planning in the commercial group led to lesser vascular and bleeding complications and shorter length of stay. PMID- 24220282 TI - Acute effects of estradiol on lung inflammation due to intestinal ischemic insult in male rats. AB - Intestinal ischemia and reperfusion (intestinal I/R) causes acute lung inflammation that is characterized by leukocyte migration, increased lung microvascular permeability, and, in severe forms, noncardiogenic pulmonary edema and acute respiratory distress syndrome. Female sex hormones interfere with immune response, and experimental and clinical evidence shows that females are more resistant than males to organ injury caused by gut trauma. To reduce the lung inflammation caused by intestinal I/R, we have acutely treated male rats with estradiol. Intestinal I/R was performed by the clamping (45 min) of the superior mesenteric artery (SMA), followed by 2 h of intestinal reperfusion (unclamping SMA). Groups of rats received 17beta estradiol (E2, 280 ug/kg, i.v., single dose) 30 min after the SMA occlusion (ischemia period) or 1 h after the unclamping of SMA (reperfusion period). Leukocytes influx into the lung and microvascular leakage were assessed by lung myeloperoxidase activity and Evans blue dye extravasation, respectively. The lung expression of adhesion molecules (intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and vascular cell adhesion molecule [VCAM]) was evaluated by immunohistochemistry. Interleukin 1beta (IL-1beta), IL-10, and NOx concentrations were quantified in supernatants of cultured lung tissue. We have found that intestinal I/R increased the lung myeloperoxidase activity and Evans blue dye extravasation, which were reduced by treatment of rats with E2. Intestinal I/R increased ICAM-1 expression only, and it was decreased by E2 treatment. However, E2 treatment reduced the basal expression of platelet endothelial cell adhesion molecule 1. E2 treatment during intestinal ischemia was effective to reduce the levels of IL-10 and IL-1beta in explant supernatant, but only IL-10 levels were reduced by E2 at reperfusion phase. The treatment with E2 did not affect NOx concentration. Taken together, our data suggest that estradiol modulates the lung inflammatory response induced by lung injury, likely by acute effects. Thus, acute estradiol treatment could be considered as a potential therapeutic agent in ischemic events. PMID- 24220283 TI - Expression of carbonic anhydrase, cystic fibrosis transmembrane regulator (CFTR) and V-H(+)-ATPase in the lancelet Branchiostoma lanceolatum (Pallas, 1774). AB - Sequencing of the amphioxus genome revealed that it contains a basic set of chordate genes involved in development and cell signaling. Despite the availability of genomic data, up till now no studies have been addressed on the comprehension of the amphioxus osmoregulation. Using primers designed on Branchiostoma floridae carbonic anhydrase (CA) II, cystic fibrosis transmembrane regulator (CFTR) and V-H(+)-ATPase, a 100bp long region, containing the protein region recognized by the respective antibodies, has been amplified and sequenced in B. lanceolatum indicating the presence of hortologous V-ATPase, CFTR and carbonic anhydrase II genes in Branchiostoma lanceolatum. Immunohistochemical results showed that all three transporting proteins are expressed in almost 90% of epithelial cells of the skin in B. lanceolatum adults with a different degree of positivity in different regions of body wall and with a different localization in the cells. The comparison of results between young and adult lancelets showed that the distribution of these transporters is quite different. Indeed, in the young specimens the expression pattern of all tested molecules appears concentrated at the gut level, whereas in adult the gut loses its key role that is mostly supported by skin. PMID- 24220284 TI - Impedance matched thin metamaterials make metals absorbing. AB - Metals are generally considered good reflectors over the entire electromagnetic spectrum up to their plasma frequency. Here we demonstrate an approach to tailor their absorbing characteristics based on the effective metamaterial properties of thin, periodic metallo-dielectric multilayers by exploiting a broadband, inherently non-resonant, surface impedance matching mechanism. Based on this mechanism, we design, fabricate and test omnidirectional, thin (<1 micron), polarization independent, extremely efficient absorbers (in principle being capable to reach A > 99%) over a frequency range spanning from the UV to the IR. Our approach opens new venues to design cost effective materials for many applications such as thermo-photovoltaic energy conversion devices, light harvesting for solar cells, flat panel display, infrared detectors, stray light reduction, stealth and others. PMID- 24220285 TI - Reduction of intermetatarsal angle after first metatarsophalangeal joint arthrodesis in patients with hallux valgus. AB - We present a radiographic review of 94 patients who underwent first metatarsophalangeal joint arthrodesis. The main focus of our review was to assess the change in the intermetatarsal angle (IMA). The change in the IMA was measured for the entire group and for 2 subgroups (IMA 11 degrees to 15 degrees and IMA >15 degrees ). The results of the angular measurements for the total data set were as follows: mean preoperative first IMA, 15.32 degrees (range 11 degrees to 24 degrees ), mean postoperative IMA, 9.88 degrees (range 3 degrees to 18 degrees ), and mean change in IMA of 5.44 degrees (range -2 degrees to 13 degrees ; p < .001). Group 1, with an IMA of 11 degrees to 15 degrees , included 52 patients, with a mean change in the IMA of 4.21 degrees (range -2 degrees to 9 degrees ; p < .001). Group 2, with an IMA greater than 15 degrees (range 16 degrees to 24 degrees ), included 42 patients, with a mean change in the IMA of 6.83 degrees (range 2 degrees to 13 degrees ; p < .001). The change in the preoperative to postoperative IMA in group 1 compared with that in group 2 was statistically significant (p < .001). The results of the present study have confirmed the observations of previous investigators that arthrodesis of the first metatarsophalangeal joint for hallux abducto valgus deformity results in a reduction of the IMA and that a proportionately larger reduction can be expected when the IMA is larger. PMID- 24220286 TI - Highly homologous eEF1A1 and eEF1A2 exhibit differential post-translational modification with significant enrichment around localised sites of sequence variation. AB - REVIEWERS: This article was reviewed by Frank Eisenhaber and Ramanathan Sowdhamini.Translation elongation factors eEF1A1 and eEF1A2 are 92% identical but exhibit non-overlapping expression patterns. While the two proteins are predicted to have similar tertiary structures, it is notable that the minor variations between their sequences are highly localised within their modelled structures. We used recently available high-throughput "omics" data to assess the spatial location of post-translational modifications and discovered that they are highly enriched on those surface regions of the protein that correspond to the clusters of sequence variation. This observation suggests how these two isoforms could be differentially regulated allowing them to perform distinct functions. PMID- 24220287 TI - Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials. AB - BACKGROUND: Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women. METHODS: We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia. RESULTS: At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found. CONCLUSIONS: CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX. PMID- 24220288 TI - C-reactive protein predicts 96-week carotid intima media thickness progression in HIV-infected adults naive to antiretroviral therapy. AB - : This is a 96-week prospective cohort study of antiretroviral therapy (ART) naive HIV-infected adults and matched healthy controls to assess progression of carotid intima media thickness (CIMT) and its relationship to inflammation. Median common carotid artery (CCA) CIMT increased significantly but similarly in both groups [CCA: 0.02 (interquartile range: 0-0.05); P < 0.01 within HIV infected adults vs. 0.01 (0-0.05) mm; P < 0.01 within controls; and P = 0.83 between groups]. Change in bulb CIMT yielded similar results. Independent predictors of CCA CIMT progression in HIV-infected adults were higher systolic blood pressure, total cholesterol, and high sensitivity C-reactive protein. Independent predictors of bulb CIMT progression were higher non-high-density lipoprotein cholesterol and high sensitivity C-reactive protein. Other inflammation markers were not associated with CIMT progression. PMID- 24220289 TI - Reversal of the Kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected Ugandans. AB - BACKGROUND: Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3-dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting. METHOD: We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIV-infected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity. RESULTS: Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets. CONCLUSIONS: Indoleamine 2,3 dioxygenase-1-mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting. PMID- 24220290 TI - TGFbeta-Mediated Downregulation of Thrombopoietin Is Associated With Platelet Decline in Asymptomatic SIV Infection. AB - BACKGROUND: Thrombocytopenia is a known consequence of HIV infection, and decreased production of platelets has been previously implicated in the pathogenesis of platelet decline during asymptomatic infection. Thrombopoietin (THPO) drives platelet production by stimulating the maturation of bone marrow megakaryocytes and can be transcriptionally downregulated by cytokines that are increased during infection such as transforming growth factor beta (TGFbeta) and platelet factor 4 (pf4). DESIGN: To determine whether transcriptional downregulation of THPO contributed to decreased platelet production during asymptomatic infection in the simian immunodeficiency virus (SIV)/macaque model of HIV, we compared hepatic THPO mRNA levels to platelet number and megakaryocyte density. To identify potential inhibitory factors that decrease THPO transcription during asymptomatic infection, we measured TGFbeta and pf4 plasma levels. To determine whether combined antiretroviral therapy (cART) could correct platelet decline by altering cytokine levels, we measured TGFbeta and pf4 in cART treated SIV-infected macaques and compared these values to cART-untreated SIV infected macaques. RESULTS: Hepatic THPO transcription was downregulated during asymptomatic SIV infection concurrent with platelet decline. Hepatic THPO mRNA levels correlated with bone marrow megakaryocyte density. In contrast, plasma TGFbeta levels were inversely correlated with hepatic THPO transcription and bone marrow megakaryocyte density. With cART treatment, plasma TGFbeta levels and platelet count returned to values similar to those in uninfected macaques. CONCLUSIONS: TGFbeta-mediated downregulation of hepatic THPO may lead to decline in platelet number during asymptomatic SIV infection, and cART may prevent platelet decline by normalizing plasma TGFbeta levels. PMID- 24220291 TI - Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer. AB - Kruppel-like factor 17 (KLF17), a member of the KLF transcription factor family, has been shown to inhibit the epithelial-mesenchymal transition (EMT) and tumor growth. However, the expression, the cellular function and the mechanism of KLF17 in endometrioid endometrial cancer (EEC; a dominant type of endometrial cancer) remain elusive. Here, we report that among the KLF family members, KLF17 was consistently upregulated in EEC cell lines compared with immortalized endometrial epithelial cells. Overexpression of KLF17 in EEC cell lines induced EMT and promoted cell invasion and drug resistance, resulting in increased expression of TWIST1. In contrast, KLF17 suppression reversed EMT, diminished cell invasion, restored drug sensitivity and suppressed TWIST1 expression. Luciferase assays, site-directed mutagenesis and transcription factor DNA-binding analysis demonstrated that KLF17 transactivates TWIST1 expression by directly binding to the TWIST1 promoter. Knockdown of TWIST1 prevented KLF17-induced EMT. Consistent with these results, both KLF17 and TWIST1 levels were found to be elevated in EECs compared with normal tissues. KLF17 expression positively correlated with tumor grade but inversely correlated with estrogen and progesterone receptor expression. Thus, KLF17 may have an oncogenic role during EEC progression via initiating EMT through the regulation of TWIST1. PMID- 24220293 TI - Detection of a charge-separated catalyst precursor state in a linked photosensitizer-catalyst assembly. AB - We have designed two new supramolecular assemblies based on Co(ii)-templated coordination of Ru(bpy)3(2+) (bpy = 2,2'-bipyridyl) analogues as photosensitizers and electron donors to a cobaloxime macrocycle, which are of interest as proton reduction catalysts. The self-assembled photocatalyst precursors were structurally characterized by Co K-edge X-ray absorption spectroscopy and solution-phase X-ray scattering. Visible light excitation of one of the assemblies has yielded instantaneous electron transfer and charge separation to form a transient Co(i) state which persists for 26 ps. The development of a linked photosensitizer-cobaloxime architecture supporting efficient Co(i) charge transfer is significant since it is mechanistically critical as the first photo induced electron transfer step for hydrogen production, and has not been detected in previous photosensitizer-cobaloxime linked dyad assemblies. X-band EPR spectroscopy has revealed that the Co(ii) centres of both assemblies are high spin, in contrast to most previously described cobaloximes, and likely plays an important role in facilitating photoinduced charge separation. Based on the results obtained from ultrafast and nanosecond transient absorption optical spectroscopies, we propose that charge recombination occurs through multiple ligand states present within the photosensitizer modules. The studies presented here will enhance our understanding of supramolecular photocatalyst assembly and direct new designs for artificial photosynthesis. PMID- 24220292 TI - Surface plasmon resonance for monitoring the interaction of Potato virus Y with monoclonal antibodies. AB - Surface plasmon resonance (SPR)-based biosensors have been widely utilized for measuring interactions of a variety of molecules. Fewer examples include higher biological entities such as bacteria and viruses, and even fewer deal with plant viruses. Here, we describe the optimization of an SPR sensor chip for evaluation of the interaction of the economically relevant filamentous Potato virus Y (PVY) with monoclonal antibodies. Different virus isolates were efficiently and stably bound to a previously immobilized polyclonal antibody surface, which remained stable over subsequent injection regeneration steps. The ability of the biosensor to detect and quantify PVY particles was compared with ELISA and RT-qPCR. Stably captured virus surfaces were successfully used to explore kinetic parameters of the interaction of a panel of monoclonal antibodies with two PVY isolates representing the main viral serotypes N and O. In addition, the optimized biosensor proved to be suitable for evaluating whether two given monoclonal antibodies compete for the same epitope within the viral particle surface. The strategy proposed in this work can help to improve existing serologic diagnostic tools that target PVY and will allow investigation of the inherent serological variability of the virus and exploration for new interactions of PVY particles with other proteins. PMID- 24220294 TI - P2Y12-receptor-inhibiting antiplatelet strategies in acute coronary syndromes. AB - Antiplatelet therapy in acute coronary syndromes is essential for preventing stent thrombosis and for reducing major adverse cardiovascular events. Treatment strategy has changed over the last years by frequent use of more active agents inhibiting the ADP mediated activation of platelets instead of clopidogrel, such as prasugrel and ticagrelor. Compared to clopidogrel these modern antiplatelet drugs showed a significant reduction of efficacy endpoints as well as an acceptable safety profile in large multicenter randomized trials (TRITON TIMI 38, PLATO). Going in with higher efficacy a generally higher bleeding risk of prasugrel could be reduced by optimizing the maintenance dose in elderly and underweight patients (TRILOGY-ACS). However even prasugrel and ticagrelor have shown a delayed onset of action in special patient populations (e.g. STEMI) suggesting that the optimal ADP inhibitor has not been found yet. Results of the CHAMPION PHOENIX trial indicate that cangrelor, an intravenous agent, might fulfill these high expectations of an ideal platelet inhibitor in the first hours of an ACS in special patient cohorts. This review summarizes the results of most important clinical studies investigating the novel P2Y12 receptor inhibiting antiplatelet drugs. PMID- 24220295 TI - Development of a primary mouse intestinal epithelial cell monolayer culture system to evaluate factors that modulate IgA transcytosis. AB - There is significant interest in the use of primary intestinal epithelial cells in monolayer culture to model intestinal biology. However, it has proven to be challenging to create functional, differentiated monolayers using current culture methods, likely due to the difficulty in expanding these cells. Here, we adapted our recently developed method for the culture of intestinal epithelial spheroids to establish primary epithelial cell monolayers from the colon of multiple genetic mouse strains. These monolayers contained differentiated epithelial cells that displayed robust transepithelial electrical resistance. We then functionally tested them by examining immunoglobulin A (IgA) transcytosis across Transwells. IgA transcytosis required induction of polymeric Ig receptor (pIgR) expression, which could be stimulated by a combination of lipopolysaccharide and inhibition of gamma-secretase. In agreement with previous studies using immortalized cell lines, we found that tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-17, and heat-killed microbes also stimulated pIgR expression and IgA transcytosis. We used wild-type and knockout cells to establish that among these cytokines, IL-17 was the most potent inducer of pIgR expression/IgA transcytosis. Interferon gamma, however, did not induce pIgR expression, and instead led to cell death. This new method will allow the use of primary cells for studies of intestinal physiology. PMID- 24220296 TI - Activation of memory Th17 cells by domain 4 pneumolysin in human nasopharynx associated lymphoid tissue and its association with pneumococcal carriage. AB - Pneumococcal carriage is common in children that may account for the high incidence of disease in this age group. Recent studies in animals suggest an important role for CD4+ T cells, T helper type 17 (Th17) cells in particular, in pneumococcal clearance. Whether this Th17-mediated mechanism operates in humans and what pneumococcal components activate Th17 are unknown. We investigated the ability of domain 4 pneumolysin (D4Ply) to activate CD4+ T cells including Th17 in human nasopharynx-associated lymphoid tissue (NALT) and peripheral blood. We show that D4Ply elicited a prominent CD4+ T-cell proliferative response. More importantly, D4Ply elicited a significant memory Th17 response in NALT, and a moderate response in peripheral blood mononuclear cells (PBMCs). This D4Ply elicited memory Th17 response was more marked in carriage- than in carriage+ children in both NALT and PBMCs. In contrast, no difference was shown in D4Ply induced Th1 response between the two groups. We also show D4Ply activated human monocytes and murine macrophages that was in part dependent on Toll-like receptor 4 (TLR-4). Our results support a protective role of Th17 against pneumococcal carriage in human nasopharynx, and identify a novel property of D4Ply to activate Th17 in NALT that may offer an attractive vaccine candidate in intranasal immunization against pneumococcal infection. PMID- 24220298 TI - TNF superfamily member TL1A elicits type 2 innate lymphoid cells at mucosal barriers. AB - Immune responses at mucosal barriers are regulated by innate type 2 lymphoid cells (ILC2s) that elaborate effector cytokines interleukins 5 and 13 (IL5 and IL13). IL25 and IL33 are key cytokines that support ILC2s; however, mice deficient in these pathways retain some functional ILC2s. Analysis of human and murine cells revealed that ILC2s highly express tumor necrosis factor (TNF) receptor superfamily member DR3 (TNFRSF25). Engagement of DR3 with cognate ligand TL1A promoted ILC2 expansion, survival, and function. Exogenous protein or genetic overexpression of TL1A activated ILC2s independent of IL25 or IL33. Dr3( /-) mice failed to control gut helminthic infections, and failed to mount ILC2 responses in the lung after nasal challenge with papain. Our data demonstrate a key role for TL1A in promoting ILC2s at mucosal barriers. PMID- 24220297 TI - Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. AB - The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein 3. Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin (POSTN), a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as POSTN. PMID- 24220299 TI - Contrasting immune responses mediate Campylobacter jejuni-induced colitis and autoimmunity. AB - Campylobacter jejuni is a leading cause of foodborne enteritis that has been linked to the autoimmune neuropathy, Guillain Barre syndrome (GBS). C57BL/6 interleukin (IL)-10(+/+) and congenic IL-10(-/-) mice serve as C. jejuni colonization and colitis models, respectively, but a mouse model for GBS is lacking. We demonstrate that IL-10(-/-) mice infected with a C. jejuni colitogenic human isolate had significantly upregulated type 1 and 17 but not type 2 cytokines in the colon coincident with infiltration of phagocytes, T cells and innate lymphoid cells (ILCs). Both ILC and T cells participated in interferon gamma (IFN-gamma), IL-17, and IL-22 upregulation but in a time- and organ specific manner. T cells were, however, necessary for colitis as mice depleted of Thy-1(+) cells were protected while neither Rag1(-/-) nor IL-10R blocked Rag1(-/ ) mice developed colitis after infection. Depleting IFN-gamma, IL-17, or both significantly ameliorated colitis and drove colonic responses toward type 2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted type 1/17 but enhanced type 2 responses. Moreover, the type 2 but not type 1/17 antibodies cross-reacted with peripheral nerve gangliosides demonstrating autoimmunity. PMID- 24220300 TI - Severe viral respiratory infections: are bugs bugging? AB - Viral respiratory tract infections (RTI) pose a high burden on the youngest members of our society. Several risk factors are known for severe viral respiratory disease. However, a large proportion of the severe RTI cannot be explained by these risk factors. A growing body of evidence shows that the composition of the microbiota has a major influence on the training of both the mucosal and the systemic immune response and can thus potentially determine susceptibility for severe viral infections. In this review, we discuss the current evidence regarding the influence of bacterial colonization on the severity of viral respiratory infections. PMID- 24220303 TI - Proteome changes induced by c-myb silencing in human chronic myeloid leukemia cells suggest molecular mechanisms and putative biomarkers of hematopoietic malignancies. AB - To shed light on the molecular mechanisms associated with aberrant accumulation of c-Myb in chronic myeloid leukemia, comparative proteomic analysis was performed on c-myb RNAi-specifically silenced K562 cells, sampled on a time course basis. 2D-DIGE technology highlighted 37 differentially-represented proteins that were further characterized by nLC-ESI-LIT-MS/MS and validated by western blotting and qRT-PCR analysis. Most of the deregulated proteins were related to protein folding, energy/primary metabolism, transcription/translation regulation and oxidative stress response. Protein network analysis suggested that glycolysis, gluconeogenesis and protein ubiquitination biosynthesis pathways were highly represented, confirming also the pivotal role of c-Myc. A specific reduced representation was observed for glyceraldehyde-3-phosphate-dehydrogenase and alpha-enolase, suggesting a possible role of c-Myb in the activation of aerobic glycolysis. A reduced amount was also observed for stress responsive heat shock 70kDa protein and 78kDa glucose-regulated protein, previously identified as direct targets of c-Myb. Among over-represented proteins, worth mentioning is the chromatin modifier chromobox protein homolog 3 that contributes to silencing of E2F- and Myc-responsive genes in quiescent G0 cells. Data here presented, while providing novel insights onto the molecular mechanisms underlying c-Myb activity, indicate potential protein biomarkers for monitoring the progression of chronic myeloid leukemia. BIOLOGICAL SIGNIFICANCE: Myeloid leukemia is a malignant disease of the hematopoietic system in which cells of myeloid lineages accumulate to an undifferentiated state. In particular, it was shown that an aberrant accumulation of the c-Myb transcriptional factor is associated with the suppression of normal differentiation processes promoting the development of the hematopoietic malignancies. Many efforts have been recently made to identify novel genes directly targeted by c-Myb at a transcriptome level. In this work, we originally describe a differential proteomic approach to facilitate the comprehension of the regulation of the protein networks exerted by c-Myb. Our study reveals a complex network of proteins regulated by c-Myb. The functional heterogeneity of these proteins emphasizes the pleiotropic role of c-Myb as a regulator of genes that are crucial for energy production and stress response in leukemia. In fact, variations in glyceraldehyde-3-phosphate-dehydrogenase and alpha-enolase suggest a possible role of c-Myb in the activation of aerobic glycolysis. Moreover, significant differences were found for heat shock 70kDa protein and 78kDa glucose-regulated protein known as direct c-Myb targets. This work highlights potential protein biomarkers to look into disease progression and to develop translational medicine approaches in myeloid leukemia. PMID- 24220302 TI - Proteome of the porosome complex in human airway epithelia: interaction with the cystic fibrosis transmembrane conductance regulator (CFTR). AB - The surface of the airways is coated with a thin film of mucus composed primarily of mucin, which is under continuous motion via ciliary action. Mucin not only serves to lubricate the airways epithelia, but also functions as a trap for foreign particles and pathogens, thereby assisting in keeping the airways clean and free of particulate matter and infections. Altered mucin secretion especially increased mucin viscosity, results in mucin stagnation due to the inability of the cilia to propel them, leading to infections and diseases such as cystic fibrosis (CF). Since porosomes have been demonstrated to be the secretory portals at the cell plasma membrane in cells, their presence, structure, and composition in the mucin-secreting human airway epithelial cell line Calu-3 expressing CF transmembrane receptor (CFTR), were investigated. Atomic force microscopy (AFM) of Calu-3 cells demonstrates the presence of approximately 100nm in diameter porosome openings at the plasma membrane surface. Electron microscopy confirms the AFM results, and tandem mass spectrometry and immunoanalysis performed on isolated Calu-3 porosomes, reveal the association of CFTR with the porosome complex. These new findings will facilitate understanding of CFTR-porosome interactions influencing mucous secretion, and provide critical insights into the etiology of CF disease. BIOLOGICAL SIGNIFICANCE: In the present study, the porosome proteome in human airway epithelia has been determined. The interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) and the porosome complex in the human airway epithelia is further demonstrated. The possible regulation by CFTR on the quality of mucus secretion via the porosome complex at the cell plasma membrane is hypothesized. These new findings will facilitate understanding of CFTR-porosome interactions influencing mucous secretion, and provide critical insights into the etiology of CF disease. PMID- 24220301 TI - Retinoic acid prevents mesenteric lymph node dendritic cells from inducing IL-13 producing inflammatory Th2 cells. AB - The vitamin A (VA) metabolite retinoic acid (RA) affects the properties of T cells and dendritic cells (DCs). In VA-deficient mice, we observed that mesenteric lymph node (MLN)-DCs induce a distinct inflammatory T helper type 2 (Th2)-cell subset that particularly produces high levels of interleukin (IL)-13 and tumor necrosis factor-alpha (TNF-alpha). This subset expressed homing receptors for skin and inflammatory sites, and was mainly induced by B220( )CD8alpha(-)CD11b(+)CD103(-) MLN-DCs in an IL-6- and OX40 ligand-dependent manner, whereas RA inhibited this induction. The corresponding MLN-DC subset of VA-sufficient mice induced a similar T-cell subset in the presence of RA receptor antagonists. IL-6 induced this subset differentiation from naive CD4(+) T cells upon activation with antibodies against CD3 and CD28. Transforming growth factor beta inhibited this induction, and reciprocally enhanced Th17 induction. Treatment with an agonistic anti-OX40 antibody and normal MLN-DCs enhanced the induction of general inflammatory Th2 cells. In VA-deficient mice, proximal colon epithelial cells produced TNF-alpha that may have enhanced OX40 ligand expression in MLN-DCs. The repeated oral administrations of a T cell-dependent antigen primed VA-deficient mice for IL-13-dependent strong immunoglobulin G1 (IgG1) responses and IgE responses that caused skin allergy. These results suggest that RA inhibits allergic responses to oral antigens by preventing MLN-DCs from inducing IL-13-producing inflammatory Th2 cells. PMID- 24220304 TI - Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease. AB - Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P<0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline. PMID- 24220305 TI - Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement. AB - BACKGROUND: Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients. METHODS: We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients. RESULTS: Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 16.5% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, = 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis. CONCLUSIONS: We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients. PMID- 24220306 TI - Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. AB - The activation of Wnt signaling has been reported in many types of squamous cell carcinoma. In this study, using human oral squamous cell carcinoma (OSCC) cells with different metastatic potential, we investigated the involvement of Wnt signaling in metastasis. Further, we aimed to elucidate the characteristic biological features related to high metastatic potential and to identify new target molecules for the suppression of OSCC lymph node metastasis. We compared SAS-Venus (SAS OSCC cells expressing green fluorescent protein) and SAS-LM8, which is a highly metastatic cell line derived from SAS-Venus by in vivo selection. The SAS-LM8 cell line had greater ability of migration and invasion compared to SAS-Venus. Furthermore, a higher number of filopodia-like protrusive structures were produced in SAS-LM8 cells compared to SAS-Venus cells, and the levels of active Cdc42 and active RhoA protein were higher in SAS-LM8 cells compared to SAS-Venus cells. We did not observe any differences in the expression of Wnt/beta-catenin target genes between the two cell lines; however, the mRNA levels of Wnt5b were higher in SAS-LM8 cells compared to SAS-Venus cells. To confirm the involvement of Wnt5b in migration in OSCC cells, we examined the effects of the siRNA-mediated knockdown of Wnt5b in SAS-Venus cells and SAS-LM8 cells. The siRNA treatment significantly inhibited migration and the formation of filopodia-like protrusive structures. Conversely, when stimulated with Wnt5b, the migration and formation of filopodia-like protrusions were significantly enhanced and the levels of active Cdc42 and active RhoA proteins were also increased. These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA. PMID- 24220307 TI - Fifteen years of the cochrane back review group. PMID- 24220308 TI - An innovative fulcrum-bending radiographical technique to assess curve flexibility in patients with adolescent idiopathic scoliosis. AB - STUDY DESIGN: A prospective clinical and radiographical study. OBJECTIVE: To introduce a redesigned fulcrum-bending radiographical (FBR) method, and to validate the effectiveness of this method in assessing patients with (AIS). SUMMARY OF BACKGROUND DATA: Several radiographical methods exist to evaluate curve flexibility in patients with AIS. The technique of FBR has been demonstrated to better predict coronal plane correction of main thoracic curves. However, the amount of weight applied may affect the results of flexibility evaluation and have not been well studied to date. METHODS: Seventeen patients with AIS with 19 curves were involved in this study. The assessment of radiographs included preoperative standing posterior-anterior, supine side bending, traditional FBR, new FBR (CH-FBR), and postoperative standing posterior anterior radiographs. CH-FBR was performed at variable device heights while measuring the applied weight at the apex. RESULTS: Preoperatively, the mean Cobb angle was 47.5 degrees +/- 8.8 degrees on the posterior-anterior radiographs, 14.3 degrees +/- 7.0 degrees on supine side-bending radiographs, 13.3 degrees +/- 5.7 degrees on traditional FBR, 11.3 degrees +/- 4.5 degrees at the lowest height using CH-FBR (lowest weight), and 7.8 degrees +/- 4.1 degrees at the optimized height using CH-FBR (maximal weight). Postoperatively, the mean Cobb angle was 9.1 degrees +/- 5.2 degrees . There was a significant difference found between supine side-bending radiograph and postoperative Cobb angle (P = 0.001), traditional FBR, and postoperative Cobb angle (P = 0.002). There was no significant difference found between optimized height CH-FBR and postoperative Cobb angle (P = 0.16). Correlation analysis indicated that the maximum height of CH-FBR positively correlated with maximum weight applied (r = 0.68, r= 0.46, P = 0.001). CONCLUSION: CH-FBR is a more reliable and effective method than traditional FBR and supine side-bending radiographs to measure curve flexibility in patients with AIS. Moreover, the flexibility suggested by the CH-FBRs more closely approximated the postoperative results from posterior pedicle screw instrumentation. LEVEL OF EVIDENCE: 3. PMID- 24220310 TI - Energy dissipation and error probability in fault-tolerant binary switching. AB - The potential energy profile of an ideal binary switch is a symmetric double well. Switching between the wells without energy dissipation requires time modulating the height of the potential barrier separating the wells and tilting the profile towards the desired well at the precise juncture when the barrier disappears. This, however, demands perfect timing synchronization and is therefore fault-intolerant even in the absence of noise. A fault-tolerant strategy that requires no time modulation of the barrier (and hence no timing synchronization) switches by tilting the profile by an amount at least equal to the barrier height and dissipates at least that amount of energy in abrupt switching. Here, we present a third strategy that requires a time modulated barrier but no timing synchronization. It is therefore fault-tolerant, error-free in the absence of thermal noise, and yet it dissipates arbitrarily small energy in a noise-free environment since an arbitrarily small tilt is required for slow switching. This case is exemplified with stress induced switching of a shape anisotropic single-domain soft nanomagnet dipole-coupled to a hard magnet. When thermal noise is present, we show analytically that the minimum energy dissipated to switch in this scheme is ~2kTln(1/p) [p = switching error probability]. PMID- 24220311 TI - Establishing the origin of metastatic deposits in the setting of multiple primary malignancies: the role of massively parallel sequencing. AB - In this proof-of-principle study, we sought to define whether targeted capture massively parallel sequencing can be employed to determine the origin of metastatic deposits in cases of synchronous primary malignancies and metastases in distinct anatomical sites. DNA samples extracted from synchronous tumor masses in the breast, adnexal, and pelvic-peritoneal regions from a 62-year-old BRCA1 germline mutation carrier were subjected to targeted massively parallel sequencing using a platform comprising 300 cancer genes known to harbor actionable mutations. In addition to BRCA1 germline mutations, all lesions harbored somatic loss of the BRCA1 wild-type allele and TP53 somatic mutations. The primary breast cancer displayed a TP53 frameshift (p.Q317fs) mutation, whereas and the adnexal lesion harbored a TP53 nonsense (p.R213*) mutation, consistent with a diagnosis of two independent primary tumors (i.e. breast and ovarian cancer). The adnexal tumor and all pelvic-peritoneal implants harbored identical TP53 (p.R213*) and NCOA2 (p.G952R) somatic mutations. Evidence of genetic heterogeneity within and between lesions was observed, both in terms of somatic mutations and copy number aberrations. The repertoires of somatic genetic aberrations found in the breast, ovarian, and pelvic-peritoneal lesions provided direct evidence in support of the distinct origin of the breast and ovarian cancers, and established that the pelvic-peritoneal implants were clonally related to the ovarian lesion. These observations were consistent with those obtained with immunohistochemical analyses employing markers to differentiate between carcinomas of the breast and ovary, including WT1 and PAX8. Our results on this case of a patient with BRCA1-mutant breast and ovarian cancer demonstrate that massively parallel sequencing may constitute a useful tool to define the relationship, clonality and intra-tumor genetic heterogeneity between primary tumor masses and their metastatic deposits in patients with multiple primary malignancies and synchronous metastases. PMID- 24220312 TI - High fat diet causes renal fibrosis in LDLr-null mice through MAPK-NF-kappaB pathway mediated by Ox-LDL. AB - BACKGROUND: Dyslipidemia, particularly increased LDL-cholesterol level in serum, is associated with atherosclerosis and fibrosis in different organs. This study was designed to investigate the effects of increase in LDL-cholesterol on renal fibrosis. METHODS: Wild-type (WT) and LDLr knockout (KO) mice were fed standard or high fat diet (HFD), and their kidneys were collected after 26 weeks of dietary intervention for identification of fibrosis and study of potential mechanisms. Additional studies were performed in cultured renal fibroblasts. RESULTS: We observed extensive and diffuse fibrosis in the kidneys of mice given HFD (P < 0.05 vs. standard chow). Fibrosis was associated with enhanced expression of fibronectin, nicotinamide adenine dinucleotide phosphate oxidases and activated p38 and p44/42 mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). There was evidence for accumulation of 4-hydroxynonenal, a lipid peroxidation product, in the kidneys and of ox-LDL in the arteries of LDLr KO mice given HFD. The expression of ox-LDL receptor LOX-1 and of transforming growth factor beta 1 (TGFbeta1) was increased in these kidneys. All these changes were more pronounced in LDLr KO mice than in the WT mice. In in vitro studies, treatment of fibroblasts from kidneys of LDLr KO mice with ox-LDL showed intense proliferation and collagen formation (all P < 0.05, fibroblasts from WT mice kidneys). Blockade of p38 MAPK, p44/42 MAPK, or NF-kappaB significantly attenuated expression of profibrotic signals, collagen formation, and proliferation of fibroblasts. CONCLUSIONS: HFD induces renal fibrosis in LDLr-null mice primarily through activation of the nicotinamide adenine dinucleotide phosphate oxidase MAPK-NF kappaB pathway by ox-LDL. PMID- 24220313 TI - Tongxinluo decreases apoptosis of mesenchymal stem cells concentration dependently under hypoxia and serum deprivation conditions through the AMPK/eNOS pathway. AB - Tongxinluo (TXL), a traditional Chinese medicine, is widely used to treat cardiovascular diseases in China. Our previous study has demonstrated the pro survival role of TXL on mesenchymal stem cells (MSCs) in vivo. But whether TXL could decrease apoptosis of MSCs in vitro, and the underlying mechanism are still unknown. Moreover, AMPK/eNOS pathway is crucial in regulating cell apoptosis. Therefore, we designed the study to investigate whether TXL could decrease MSCs apoptosis under hypoxia and serum deprivation (H/SD) conditions and to determine the role of AMPK/eNOS pathway. To test the hypothesis, MSCs were treated with TXL (50-400 MUg/mL) under H/SD for 6 hours. For inhibitor studies, the cells were preincubated with AMPK inhibitor compound C. Results indicated that TXL decreased MSCs apoptosis concentration-dependently evidenced by reduced Annexin V+/PI- cells and increased red/green ratio of JC-1. Further, TXL enhanced the phosphorylation of AMPK and eNOS. Whereas, treatment with compound C decreased the phosphorylation of AMPK and eNOS and was accompanied by attenuated anti apoptotic effect of TXL. In conclusion, TXL protected MSCs against H/SD-induced injury at least in part through the AMPK/eNOS pathway, which provides a novel explanation for the multi-effect of TXL on cardiovascular system. PMID- 24220314 TI - Effects of Na+ channel blockers on extrasystolic stimulation-evoked changes in ventricular conduction and repolarization. AB - Antiarrhythmic agents which belong to class Ia (quinidine) and Ic (flecainide) reportedly increase propensity to ventricular tachyarrhythmia, whereas class Ib agents (lidocaine and mexiletine) are recognized as safe antiarrhythmics. Clinically, tachyarrhythmia is often initiated by a premature ectopic beat, which increases spatial nonuniformities in ventricular conduction and repolarization thus facilitating reentry. This study examined if electrical derangements evoked by premature excitation may be accentuated by flecainide and quinidine, but unchanged by lidocaine and mexiletine, which would explain the difference in their safety profile. In perfused guinea pig hearts, a premature excitation evoked over late repolarization phase was associated with prolonged epicardial activation time, reduced monophasic action potential duration (APD), and increased transepicardial dispersion of the activation time and APD. Flecainide and quinidine increased conduction slowing evoked by extrasystolic stimulation, prolonged APD, and accentuated spatial heterogeneities in ventricular conduction and repolarization associated with premature excitation. Spontaneous episodes of nonsustained monomorphic ventricular tachycardia were observed in 50% of heart preparations exposed to drug infusion. In contrast, lidocaine and mexiletine had no effect on extrasystolic stimulation-evoked changes in ventricular conduction and repolarization or arrhythmic susceptibility. These findings suggest that flecainide and quinidine may promote arrhythmia by exaggerating electrophysiological abnormalities evoked by ectopic beats. PMID- 24220315 TI - Cardioprotective effect of VEGF and venom VEGF-like protein in acute myocardial ischemia in mice: effect on mitochondrial function. AB - Coronary endothelial dysfunction is involved in cardiac ischemia-reperfusion (IR) injury. Vascular endothelial growth factor (VEGF) activates endothelial cells and exerts cardioprotective effects in isolated hearts. The recently discovered viper venom protein called increasing capillary permeability protein (ICPP) exerts VEGF like effects in endothelial cells. We examined whether VEGF or ICPP can influence IR outcome in vivo in mice. Dosages of VEGF and ICPP were determined by preliminary blood pressure study. In IR, both the proteins administered intravenously at reperfusion reduced infarct size (IS) by 57% for VEGF and 52% for ICPP (P < 0.01). Pretreatment with a selective VEGFR2 receptor antagonist abolished the reduction in IS. VEGF and ICPP induced ERK phosphorylation in the myocardium. IR triggered mitochondrial pore opening and impaired mitochondrial respiratory function. These effects of IR were prevented by VEGF or ICPP, which increased mitochondrial calcium retention capacity by 37% compared with saline (P < 0.05) and improved mitochondrial respiratory function (by 71% and 65%, respectively for state 3, and 51% and 38% for state 4, P < 0.01 for VEGF). Thus, intravenous administration of VEGF or ICPP at reperfusion largely reduces IS in IR, through stimulation of VEGFR2 receptors. This effect is mediated, at least in part, by improvement of IR-induced mitochondrial dysfunction. PMID- 24220316 TI - Does modifying the thick texture and creamy flavour of a drink change portion size selection and intake? AB - Previous research indicates that a drink's sensory characteristics can influence appetite regulation. Enhancing the thick and creamy sensory characteristics of a drink generated expectations of satiety and improved its actual satiating effects. Expectations about food also play an important role in decisions about intake, in which case enhancing the thick and creamy characteristics of a drink might also result in smaller portion size selection. In the current study forty eight participants (24 female) completed four test days where they came into the laboratory for a fixed-portion breakfast, returning two hours later for a mid morning drink, which they could serve themselves and consume as much as they liked. Over the test days, participants consumed an iso-energetic drink in four sensory contexts: thin and low-creamy; thin and high-creamy; thick and low creamy; thick and high-creamy. Results indicated that participants consumed less of the thick drinks, but that this was only true of the female participants; male participants consumed the same amount of the four drinks regardless of sensory context. The addition of creamy flavour did not affect intake but the thicker drinks were associated with an increase in perceived creaminess. Despite differences in intake, hunger and fullness ratings did not differ across male and female participants and were not affected by the drinks sensory characteristics. The vast majority of participants consumed all of the drink they served themselves indicating that differences in intake reflected portion size decisions. These findings suggest women will select smaller portions of a drink when its sensory characteristics indicate that it will be satiating. PMID- 24220318 TI - A novel mutation in IFN-gamma receptor 1 presenting as multisystem Mycobacterium intracellulare infection. PMID- 24220317 TI - Increased density of intraepithelial mast cells in patients with exercise-induced bronchoconstriction regulated through epithelially derived thymic stromal lymphopoietin and IL-33. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is a prototypical feature of indirect airway hyperresponsiveness. Mast cells are implicated in EIB, but the characteristics, regulation, and function of mast cells in patients with EIB are poorly understood. OBJECTIVES: We sought to examine mast cell infiltration of the airway epithelium in patients with EIB and the regulation of mast cell phenotype and function by epithelially derived cytokines. METHODS: Endobronchial biopsy specimens, epithelial brushings, and induced sputum were obtained from asthmatic patients with and without EIB and healthy control subjects. Mast cell proteases were quantified by using quantitative PCR, and mast cell density was quantified by using design-based stereology. Airway epithelial responses to wounding and osmotic stress were assessed in primary airway epithelial cells and ex vivo murine lung tissue. Mast cell granule development and function were examined in cord blood-derived mast cells. RESULTS: Tryptase and carboxypeptidase A3 expression in epithelial brushings and epithelial mast cell density were selectively increased in the asthma group with EIB. An in vitro scratch wound initiated the release of thymic stromal lymphopoietin, which was greater in epithelial cells derived from asthmatic patients. Osmotic stress induced the release of IL-33 from explanted murine lungs, which was increased in allergen treated mice. Thymic stromal lymphopoietin combined with IL-33 increased tryptase and carboxypeptidase A3 immunostaining in mast cell precursors and selectively increased cysteinyl leukotriene formation by mast cells in a manner that was independent of in vitro sensitization. CONCLUSIONS: Mast cell infiltration of the epithelium is a critical determinant of indirect airway hyperresponsiveness, and the airway epithelium might serve as an important regulator of the development and function of this mast cell population. PMID- 24220319 TI - Flow diversion: exciting new technology in its infancy. PMID- 24220321 TI - Neurosurgical recruitment: the gold rush. PMID- 24220320 TI - Rhabdoid sarcoma of the brain in adults: which treatment? PMID- 24220322 TI - Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. AB - As prepared nanomaterials of metals, semiconductors, polymers and carbon often need surface modifications such as ligand exchange, and chemical and bioconjugate reactions for various biosensor, bioanalytical, bioimaging, drug delivery and therapeutic applications. Such surface modifications help us to control the physico-chemical, toxicological and pharmacological properties of nanomaterials. Furthermore, introduction of various reactive functional groups on the surface of nanomaterials allows us to conjugate a spectrum of contrast agents, antibodies, peptides, ligands, drugs and genes, and construct multifunctional and hybrid nanomaterials for the targeted imaging and treatment of cancers. This tutorial review is intended to provide an introduction to newcomers about how chemical and bioconjugate reactions transform the surface of nanomaterials such as silica nanoparticles, gold nanoparticles, gold quantum clusters, semiconductor quantum dots, carbon nanotubes, fullerene and graphene, and accordingly formulate them for applications such as biosensing, bioimaging, drug and gene delivery, chemotherapy, photodynamic therapy and photothermal therapy. Nonetheless, controversial reports and our growing concerns about toxicity and pharmacokinetics of nanomaterials suggest the need for not only rigorous in vivo experiments in animal models but also novel nanomaterials for practical applications in the clinical settings. Further reading of original and review articles cited herein is necessary to buildup in-depth knowledge about the chemistry, bioconjugate chemistry and biological applications of individual nanomaterials. PMID- 24220324 TI - Diagnostic performance of 18F-FDG PET/CT, ultrasonography and MRI. Detection of axillary lymph node metastasis in breast cancer patients. AB - The aim of this study was to evaluate the diagnostic abilities of 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography(PET/CT) compared with those of ultrasonography and magnetic resonance imaging (MRI) for axillary lymph node staging in breast cancer patients. PATIENTS, METHODS: Preoperative 18F-FDG PET/non-contrast CT, ultrasonography and MRI were performed in 215 women with breast cancer. Axillary lymph node dissection was performed in all patients and the diagnostic performance of each modality was evaluated using histopathologic assessments as the reference standard. ROC curves were compared to evaluate the diagnostic ability of several imaging modalities (i. e., ultrasonography, MRI and 18F-FDG PET/CT). RESULTS: In total, 132 patients (61.4%) had axillary lymph node metastasis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the detection of axillary lymph node metastasis were 72.3%, 77.3%, 66.7%, 81.6%, 75.3% for ultrasonography, 67.5%, 78.0%, 65.9%, 79.2%, 74.0% for MRI, and 62.7%, 88.6%, 77.6%, 79.1%, 78.6% for 18F-FDG PET/CT, respectively. There was no significant difference in diagnostic ability among the imaging modalities (i.e., ultrasonography, MRI and 18F-FDG PET/CT). The diagnostic ability of 18F-FDG PET/CT was significantly improved by combination with MRI (p = 0.0002) or ultrasonography (p < 0.0001). The combination of 18F-FDG PET/CT with ultrasonography had a similar diagnostic ability to that of all three modalities combined (18F-FDG PET/CT+ultrasonography+MRI, p = 0.05). CONCLUSION: The diagnostic performance of 18F-FDG PET/CT for detection of axillary node metastasis was not significantly different from that of ultrasonography or MRI in breast cancer patients. Combining 18F-FDG PET/CT with ultrasonography or MRI could improve the diagnostic performance compared to 18F-FDG PET/CT alone. PMID- 24220323 TI - Genetically modified hematopoietic stem cell transplantation for HIV-1-infected patients: can we achieve a cure? AB - The cure of a human immunodeficiency virus (HIV)-1-infected patient following allogeneic transplantation from a CCR5-null donor and potential cure of two patients transplanted with CCR5 wild-type hematopoietic stem cells (HSC) have provided renewed optimism that a potential alternative to conventional antiretroviral therapy (ART) is forthcoming. While allogeneic grafts have thus far suggested complete eradication of viral reservoirs, it has yet to be observed following autologous HSC transplantation. Development of curative autologous transplantation strategies would significantly increase the number of treatable patients, eliminating the need for matched donors and reducing the risks of adverse events. Recent studies suggest gene therapy may provide a mechanism for developing curative therapies. Expression of cellular/artificial restriction factors or disruption of CCR5 has been shown to limit viral replication and provide protection of genetically modified cells. However, significant obstacles remain with regards to the depletion of established viral reservoirs in an autologous transplantation setting devoid of the "allo-effect". Here, we discuss results from early-stage clinical trials and recent findings in animal models of gene modified HSC transplantation. Finally, we propose innovative combination therapies that may aid in the reduction and/or elimination of viral reservoirs in HIV-1-infected patients and promote the artificial development of a natural controller phenotype. PMID- 24220325 TI - A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells. AB - BACKGROUND: Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II) complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells. METHODS: P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model. RESULTS: The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier. CONCLUSIONS: Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth. PMID- 24220327 TI - Application of a new technique, spiral tissue microarrays constructed using needle biopsy specimens, to prostate cancer research. AB - Tissue microarrays were constructed using prostate needle biopsy specimens obtained from 58 patients who underwent radical prostatectomy for localized or locally advanced prostate cancer (PC). We used the spiral array (SA) technique, a novel approach for tissue array construction in a spiral form, which has advantages over small needle biopsy specimens. Roll-shaped tissue pieces produced by slicing a prostate biopsy tissue block and trimming the cancer segment were used to obtain a tissue array block. Cancer segments measuring >3 mm were incorporated into the tissue arrays. Cancer fragments (n=253) were obtained from formalin-fixed, paraffin-embedded needle biopsy specimens. The median number of cancer fragments per patient was four (1-8, min-max). On SA, the median number of confirmed cancer fragments per patient was four (1-7) and 224 cancer fragments (88.5%) were confirmed histologically. Each core of reeled tissue contained at least one cancer fragment. The expressions of multiple prognostic molecular markers for PC (Ki-67, p53 and bcl-2) were immunohistochemically measured using the SA. The Ki-67 and bcl-2 expressions were significantly associated with the Gleason score (GS). A univariate analysis identified Ki-67, bcl-2 and GS as significant predictors of cancer-specific survival, p53 and bcl-2 as significant predictors of overall survival and Ki-67, adjuvant androgen deprivation and GS as significant predictors of biochemical progression. In a multivariate analysis, p53 was independently associated with overall survival, while adjuvant androgen deprivation and GS were associated with biochemical progression. These results indicate that SA has potential as a new tool for translational research on PC. PMID- 24220326 TI - Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age. AB - BACKGROUND: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). RESULTS: Four doses of MenACWY-CRM induced hSBA titers >=8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers >=8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. CONCLUSION: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. METHODS: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID- 24220328 TI - Energy and lipid metabolism gene expression of D18 embryos in dairy cows is related to dam physiological status. AB - We analyzed the change in gene expression related to dam physiological status in day (D)18 embryos from growing heifers (GH), early lactating cows (ELC), and late lactating cows (LLC). Dam energy metabolism was characterized by measurement of circulating concentrations of insulin, glucose, IGF-1, nonesterified fatty acids, beta-hydroxybutyrate, and urea before embryo flush. The metabolic parameters were related to differential gene expression in the extraembryonic tissues by correlation analysis. Embryo development estimated by measuring the length of the conceptuses and the proportion of expected D18 gastrulating stages was not different between the three groups of females. However, embryo metabolism was greatly affected by dam physiological status when we compared GH with ELC and GH with LLC but to a lesser extent when ELC was compared with LLC. Genes involved in glucose, pyruvate, and acetate utilization were upregulated in GH vs. ELC conceptuses (e.g., SLC2A1, PC, ACSS2, ACSS3). This was also true for the pentose pathway ( PGD, TKT), which is involved in synthesis of ribose precursors of RNA and DNA. The pathways involved in lipid synthesis were also upregulated in GH vs. ELC. Despite similar morphological development, the molecular characteristics of the heifers' embryos were consistently different from those of the cows. Most of these differences were strongly related to metabolic/hormone patterns before insemination and during conceptus free-life. Many biosynthetic pathways appeared to be more active in heifer embryos than in cow embryos, and consequently they seemed to be healthier, and this may be more conducive to continue development. PMID- 24220329 TI - Bovine beta-defensin gene family: opportunities to improve animal health? AB - Recent analysis of the bovine genome revealed an expanded suite of beta-defensin genes that encode what are referred to as antimicrobial or host defense peptides (HDPs). Whereas primate genomes also encode alpha- and theta-defensins, the bovine genome contains only the beta-defensin subfamily of HDPs. beta-Defensins perform diverse functions that are critical to protection against pathogens but also in regulation of the immune response and reproduction. As the most comprehensively studied subclass of HDPs, beta-defensins possess the widest taxonomic distribution, found in invertebrates as well as plants, indicating an ancient point of origin. Cross-species comparison of the genomic arrangement of beta-defensin gene repertoire revealed them to vary in number among species presumably due to differences in pathogenic selective pressures but also genetic drift. beta-Defensin genes exist in a single cluster in birds, but four gene clusters exist in dog, rat, mouse, and cow. In humans and chimpanzees, one of these clusters is split in two as a result of a primate-specific pericentric inversion producing five gene clusters. A cluster of beta-defensin genes on bovine chromosome 13 has been recently characterized, and full genome sequencing has identified extensive gene copy number variation on chromosome 27. As a result, cattle have the most diverse repertoire of beta-defensin genes so far identified, where four clusters contain at least 57 genes. This expansion of beta defensin HDPs may hold significant potential for combating infectious diseases and provides opportunities to harness their immunological and reproductive functions in commercial cattle populations. PMID- 24220330 TI - Lipid composition of membrane rafts, isolated with and without detergent, from the spleen of a mouse model of Gaucher disease. AB - Biological membranes are composed of functionally relevant liquid-ordered and liquid-disordered domains that coexist. Within the liquid-ordered domains are low density microdomains known as rafts with a unique lipid composition that is crucial for their structure and function. Lipid raft composition is altered in sphingolipid storage disorders, and here we determined the lipid composition using a detergent and detergent-free method in spleen tissue, the primary site of pathology, in a mouse model of the sphingolipid storage disorder, Gaucher disease. The accumulating lipid, glucosylceramide, was 30- and 50-fold elevated in the rafts with the detergent and detergent-free method, respectively. Secondary accumulation of di- and trihexosylceramide resided primarily in the rafts with both methods. The phospholipids distributed differently with more than half residing in the rafts with the detergent-free method and less than 10% with the detergent method, with the exception of the fully saturated species that were primarily in the rafts. Individual isoforms of sphingomyelin correlated with detergent-free extraction and more than half resided in the raft fractions. However, this correlation was not seen with the detergent extraction method as sphingomyelin species were spread across both the raft and non-raft domains. Therefore caution must be exercised when interpreting phospholipid distribution in raft domains as it differs considerably depending on the method of isolation. Importantly, both methods revealed the same lipid alterations in the raft domains in the spleen of the Gaucher disease mouse model highlighting that either method is appropriate to determine membrane lipid changes in the diseased state. PMID- 24220331 TI - Early postnatal maternal separation causes alterations in the expression of beta3 adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity. AB - The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague-Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3h each day during the 10-15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), beta3-adrenergic receptor (beta3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through beta3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the beta3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life. PMID- 24220332 TI - Disease-associated single amino acid mutation in the calf-1 domain of integrin alpha3 leads to defects in its processing and cell surface expression. AB - Integrin alpha3beta1, a receptor for laminins, is involved in the structural and functional organization of epithelial organs, including the lung, kidney, and skin. Recently, a missense mutation that causes substitution of Arg628 with Pro (R628P) in the calf-1 domain of human alpha3 was shown to be associated with disorders of the lung, kidney, and skin. Here, we found that the R628P mutation leads to aberrations in the posttranslational processing of alpha3. Specifically, alpha3 with the R628P mutation showed hardly any cleavage at the calf-2 domain, which usually occurs in the Golgi apparatus during the delivery of de novo synthesized alpha3. The mutant alpha3 retained the ability to associate with integrin beta1, but not with the tetraspanin CD151, and the bound beta1 was a partially glycosylated immature form, the maturation of which also takes place in the Golgi apparatus. Furthermore, the cell surface expression of the mutant protein was markedly reduced. These results suggest that the R628P mutation leads to a deficit in the transport of alpha3beta1 from the ER to the Golgi apparatus. When Arg628 was mutated to Gln or Glu, instead of Pro, the resulting mutants did not display aberrations in processing or CD151 binding, indicating that the presence of Pro, rather than the absence of Arg, at amino acid residue 628 of alpha3 is important for the abnormalities in the R628P mutant. In support of this notion, a homology modeling analysis of the calf-1 domain of alpha3 showed that replacement with Pro, but not with Gln or Glu, caused partial disruption of the beta-sheet structures. Furthermore, the ER-associated degradation of the R628P mutant was not enhanced compared with that of the wild-type protein, suggesting that the deficits in the posttranslational processing and cell surface expression of the R628P mutant are independent of the ER-associated degradation, but arise from the defect in its export from the ER. We conclude that the calf-1 domain is required for the transport of alpha3 from the ER to the Golgi apparatus to maintain the integrity of epithelial tissues, and hence the impairment of the calf-1 domain by the R628P mutation leads to severe diseases of the kidneys, lungs, and skin. PMID- 24220334 TI - Dynamic expression pattern of Pde4d and its relationship with CpG methylation in the promoter during mouse embryo development. AB - Mouse Pde4d is located on chromosome 13 and serves many functions in important physiological processes involving cyclic adenosine monophosphate. In this study, imprinting analysis indicated that Pde4d exhibits a dynamic and specific allelic expression pattern during embryo development. This showed paternal-origin sex bias in embryonic day 9.5 (E9.5) whole embryos and placenta, and biallelic expression in the major embryonic organs and placenta at E15.5. In situ hybridization determined the spatiotemporal expression pattern of Pde4d in mouse embryos from the mid- to late-embryonic stages. This demonstrated that Pde4d was widely expressed in the neural tissues, including the forebrain, midbrain, hindbrain, and neural tube, at the mid-embryonic stage. By the late-embryonic stage, Pde4d was extensively detected throughout the developing organism, including in the liver, brain, lung, kidney, and tongue. In addition, methylation analyses indicated that tissue-specific CpG methylation of the Pde4d promoter was correlated with Pde4d mRNA expression in major E15.5 tissues. Furthermore, stage specific CpG methylation of the Pde4d promoter was associated with gene expression in the liver at three developmental stages. Our results suggest that Pde4d might serve specific biological functions in regulating the development process of the mouse embryo, and that CpG methylation of the Pde4d promoter may play an important role in regulating Pde4d at a transcriptional level. PMID- 24220333 TI - Identification of an enhancer region for immune activation in the human GTP cyclohydrolase I gene. AB - GTP cyclohydrolase I (GCH) catalyzes the first and rate limiting step reaction for the de novo synthesis of 5,6,7,8-tetrahydrobiopterin (BH4). The expression of GCH is dramatically elevated by immune activation, while the mechanism remains to be elucidated. In this study, we investigated the transcription mechanism of the GCH gene using lipopolysaccharide (LPS) to stimulate mouse macrophage RAW264.7 cells. With luciferase assay, we found a highly conserved enhancer region spanning approximately 300 bp in intron 1 of GCH gene as a response element to LPS stimulation. The same enhancer region was also responsible for the induction of the GCH gene by IFN-gamma and TNF-alpha in HUVECs. With electrophoresis mobility shift assay (EMSA) and site directed mutation analysis, we identified two key fragments containing C/EBP and Ets binding motifs within the enhancer. Furthermore, C/EBP-beta was involved in LPS activated GCH transcription through direct binding to the enhancer shown by supershift, chromatin immunoprecipitation, and RNA interference experiments. In conclusion, our findings uncovered a novel mechanism of GCH transcriptional regulation by immune activation. PMID- 24220335 TI - LC3B-II deacetylation by histone deacetylase 6 is involved in serum-starvation induced autophagic degradation. AB - Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation. PMID- 24220336 TI - NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL. AB - The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1 BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1 BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1 BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated. PMID- 24220337 TI - Identification of mitogen-activated protein kinase kinase gene family and MKK MAPK interaction network in maize. AB - Plant mitogen-activated protein kinases (MAPK) are involved in important processes, including stress signaling and development. MAPK kinases (MAPKK, MKK) have been investigated in several plant species including Arabidopsis thaliana, Oryza sativa, Populus trichocarpa, and Brachypodium distachyon. In the present study, nine putative maize MKK genes have been identified. Analysis of the conserved protein motifs, exon-intron junctions and intron phase has revealed high levels of conservation within the phylogenetic groups. Next, we defined four new ZmMKK-ZmMPK interactions using yeast two-hybrid. Finally, we examined the biological functions of the ZmMKK4 gene. Overexpression of ZmMKK4 in Arabidopsis conferred tolerance to oxidative stress by increased germination rate and early seedling growth compared with WT plants. Taken together, we provide a comprehensive bioinformatics analysis of the MKK gene family in maize genome and our data provide an important foundation for further functional study of MAPK and MKK families in maize. PMID- 24220338 TI - Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement. AB - Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM. PMID- 24220339 TI - MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos. AB - MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR 490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell lines with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos. PMID- 24220340 TI - Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface. AB - Lipoprotein lipase (LPL) and angiopoietin-like protein 4 (Angptl4) were studied in 3T3-L1 adipocytes. Transfections of the adipocytes with Angptl4 esiRNA caused reduction of the expression of Angptl4 to about one fourth of that in cells treated with vehicle only. This resulted in higher levels of LPL activity both on cell surfaces (heparin-releasable) and in the medium, while LPL activity within the cells remained unaffected. This demonstrated that even though both proteins are made in the same cell, Angptl4 does not inactivate LPL during intracellular transport. Most of the Angptl4 protein was present as covalent dimers and tetramers on cell surfaces, while within the cells there were only monomers. LPL gradually lost activity when incubated in medium, but there was no marked difference between conditioned medium from normal cells (rich in Angptl4) and medium after knockdown of Angptl4. Hence Angptl4 did not markedly accelerate inactivation of LPL in the medium. Experiments with combinations of different cells and media indicated that inactivation of LPL occurred on the surfaces of cells producing Angptl4. PMID- 24220341 TI - MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway. AB - MicroRNAs (miRNAs) are fundamental regulators of cell proliferation, differentiation, and apoptosis, and are implicated in tumorigenesis of many cancers. MiR-34a is best known as a tumor suppressor through repression of growth factors and oncogenes. Growth arrest specific1 (GAS1) protein is a tumor suppressor that inhibits cancer cell proliferation and induces apoptosis through inhibition of RET receptor tyrosine kinase. Both miR-34a and GAS1 are frequently down-regulated in various tumors. However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date. A computational search revealed that miR-34a putatively binds to the 3'-UTR of GAS1 gene. In the present study, we confirmed previous findings that miR-34a is up-regulated and GAS1 down regulated in PTC tissues. Further studies indicated that GAS1 is directly targeted by miR-34a. Overexpression of miR-34a promoted PTC cell proliferation and colony formation and inhibited apoptosis, whereas knockdown of miR-34a showed the opposite effects. Silencing of GAS1 had similar growth-promoting effects as overexpression of miR-34a. Furthermore, miR-34a overexpression led to activation of PI3K/Akt/Bad signaling pathway in PTC cells, and depletion of Akt reversed the pro-growth, anti-apoptotic effects of miR-34a. Taken together, our results demonstrate that miR-34a regulates GAS1 expression to promote proliferation and suppress apoptosis in PTC cells via PI3K/Akt/Bad pathway. MiR-34a functions as an oncogene in PTC. PMID- 24220342 TI - A new model of integrated primary-secondary care for complex diabetes in the community: study protocol for a randomised controlled trial. AB - BACKGROUND: A new model of complex diabetes care is provided by a multidisciplinary team which incorporates general practitioner (GP) Clinical Fellows supported by an Endocrinologist and diabetes educator within a community based general practice setting. This study evaluates the health and clinical benefits of the new model of care, assesses the acceptability of the model to patients, GPs and other health professionals, and examines the cost-effectiveness of the model. METHODS/DESIGN: The study is an open, non-inferiority randomised controlled trial with data collected at baseline, 6 and 12 months. Participants are identified from new patients on hospital-based diabetes outpatient clinic waiting lists and new GP referrals. Eligible consenting patients are randomised to either a community practice site (intervention) or a hospital site (usual care). In the intervention model, medical care is led by a GP Clinical Fellow in partnership with an Endocrinologist. Quantitative measures include clinical indicators with HbA1c as the primary outcome; patient-reported outcomes include health-related quality of life, mental health and satisfaction with care. Qualitative methods will be used to explore the perspectives and experiences of patients and providers regarding the new model of care. An economic evaluation will also be undertaken. DISCUSSION: This model of care seeks to improve the quality and safety of healthcare at the interface between the hospital and primary care sectors for patients with complex diabetes. The study will provide empirical evidence about the impact of the model of care on health outcomes, patient and clinician satisfaction, as well as any economic impacts. TRIAL REGISTRATION: Clinical Trials Registry Number: ACTRN12612000380897. PMID- 24220343 TI - Permanent contact with females increases testosterone and improves fresh semen traits in pampas deer (Ozotoceros bezoarticus) males. AB - Socio-sexual signals can stimulate neuroendocrinal control of reproduction. The aim of this work was to test the hypothesis that permanent and close contact with females stimulates testosterone production and enhances fresh seminal characteristics of pampas deer males. Five adult males (group CF) were established in a paddock in five breeding groups each comprising one stag and between five and ten hinds. Six adult males (group IS) were held in another paddock without any direct contact with females. Fecal testosterone concentrations were determined for each male, weekly, from October to May. Semen was collected by electro-ejaculation and evaluated before and after the addition of diluents [November: Fructose-Tris-Glycine with 20% egg yolk (FTG); April: Andromed]. Males in contact with females from mid-December to February exhibited significantly (P=0.04) greater concentrations of testosterone than those without. In November, CF males ejaculated semen of significantly (P=0.03) higher quality, with a significantly (P=0.02) greater proportion of progressive motile spermatozoa than IS males. After dilution with FTG, semen from the CF males had greater quality (P=0.04), a greater percentage of motile spermatozoa (P=0.04), spermatozoa with progressive motility (P=0.01), and spermatozoa with intact acrosomes (P=0.03). Semen from CF males also had lower fractions of spermatozoa with damaged acrosomes (P=0.04). In April, there were no significant differences in semen properties between the two groups. After the addition of extender, semen from CF males had a greater percentage of spermatozoa with damaged acrosomes (P=0.04). It is concluded that contact with females stimulates reproductive patterns of male pampas deer, resulting in better fresh semen characteristics before rutting and higher testosterone concentrations during the rut. PMID- 24220344 TI - Integration of TiO2 into the diatom Thalassiosira weissflogii during frustule synthesis. AB - Nature has inspired the design of complex hierarchical structures in the field of material science. Diatoms, unicellular algae with a hallmark intricate siliceous cell wall, have provided such a stimulus. Altering the chemistry of the diatom frustule has been explored to expand on the potential application of diatoms. The ability to modify the diatom in vivo opens the possibility to tailor the diatom to the end application. Herein, we report the chemical modification of the living diatom T. weissflogii using a titania precursor, titanium (IV) bis-(ammonium lactato)-dihydroxide (TiBALDH). Incorporation of Ti into the diatom is achieved via repeated treatment of cultures with non-toxic concentrations of TiBALDH. The characteristic architectural features of the diatom are unaltered following chemical modification. Transformation of the living diatom provides opportunity to confer novel structural, chemical or functional properties upon the diatom. We report on a photocatalytic ability imparted upon the TiBALDH-modified diatom. PMID- 24220345 TI - Au nanoparticle-modified DNA sensor based on simultaneous electrochemical impedance spectroscopy and localized surface plasmon resonance. AB - Electrochemical impedance spectroscopy (EIS) and localized surface plasmon resonance (LSPR) were performed on the same Au nanoparticle (AuNP)-modified indium tin oxide (ITO) coated glass surfaces. Cyclic voltammetry was applied to electrodeposit AuNPs on ITO surface directly. The surface plasmon band characterization of AuNPs was initially studied by controlling the electrodeposition conditions. It was found that the size of AuNP clusters was significantly affected by the applied potential and KCl concentration in solution. The dual-detection platform was applied to detect DNA hybridization related to a specific point mutation in apolipoprotein E gene (ApoE), which was related to the progression of Alzheimer's disease. The preliminary results facilitate the development of a versatile biosensor that can be easily miniaturized and integrated into a high-throughput diagnostic device. PMID- 24220346 TI - A filter-like AuNPs@MS SERS substrate for Staphylococcus aureus detection. AB - An accurate, highly sensitive and rapid identification assay of cells is extremely important in areas such as medical diagnosis, biological research, and environmental monitoring. Laboratory examinations of clinical isolates require time-consuming and complex processes to identify the colony count, with approximately 10(6)-10(8) cells needed for the characterization of strains. In the present study, a highly sensitive SERS filter-like substrate is prepared with AuNPs embedded in mesoporous silica (denoted as AuNPs@MS) synthesized by a simple one-spot method, and an example of its use for the filtration and concentration of analytes from aqueous samples is reported. In an application for Staphylococcus aureus SERS discrimination, the results show that the target cells can be concentrated on the filter-like AuNPs@MS substrates within a few seconds, with much better reproducibility with regard to the SERS spectra that are obtained. The experimental findings suggest that the AuNPs@MS substrate supports much higher intensity with more distinguishable peaks compared to Au/Cr-coated substrate, and the reproducibility is also significantly improved. The substrates investigated in this study generated 900 times more SERS signals at a concentration of 10(6)CFU/mL in the detection of S. aureus on mesoporous silica (Au wt%=0) when using AuNPs@MS with 16 wt% AuNPs. The limitation of this filter like SERS substrate can be applicable for small volume samples (few to hundred microliter). PMID- 24220347 TI - Finite element analysis of equine incisor teeth. Part 1: determination of the material parameters of the periodontal ligament. AB - In equine dentistry, periodontal diseases are frequently found in aged horses. Excessive strains and stresses within the periodontal ligament (PDL) occurring during the masticatory cycle may be predisposing factors especially in old horses with short, worn teeth. The finite element (FE) analysis is a valuable tool to investigate such strains and stresses in biological materials but a precondition for a realistic and reliable FE analysis is accurate knowledge of material parameters. As no data exist concerning the PDL of equine incisor teeth, this study was undertaken to determine the equine specific, age related and load dependent Young's modulus of equine incisors. To determine the biomechanical behaviour of the PDL, the incisor jaw-regions of horses of different ages were sectioned into 5mm thick slice samples and the incisors experimentally intruded (i.e. axially displaced into the alveolus) while recording the load-displacement relationship. Based on high resolution micro-computer tomography (MUCT)-datasets, reliable and detailed 3-dimensional models of the slice samples were constructed focusing on precisely modelling the anatomy of the PDL. FE calculations were then performed and set-actual comparisons of the FE results with the experimentally measured displacements enabled the Young's modulus of the PDL to be determined. The results of this study reflect the typical non-linear behaviour of the collagen fibres of the PDL and present a high load dependency of the PDL's Young's modulus. Further investigations calculating the strains and stresses within the periodontal ligament, teeth and surrounding bone of the entire rostral aspect of the jaw are warranted. PMID- 24220348 TI - The legacy of sexually transmitted disease research: lessons from Guatemala and Dr. Thomas Parran: the American STD Association Distinguished Career Award Lecture. PMID- 24220349 TI - Scale-up and case-finding effectiveness of an HIV partner services program in Cameroon: an innovative HIV prevention intervention for developing countries. AB - BACKGROUND: Partner services (PSs) are a long-standing component of HIV control programs in the United States and some parts of Europe. Small randomized trials suggest that HIV PS can be effective in identifying persons with undiagnosed HIV infection. However, the scalability and effectiveness of HIV PS in low-income countries are unknown. METHODS: We used data collected from 2009 to 2010 through a large HIV PS program in Cameroon to evaluate HIV PS in a developing country. HIV-positive index cases diagnosed in antenatal care, voluntary counseling and testing, and inpatient facilities were interviewed to collect information on their sexual partners. Partners were contacted via telephone or home visit to notify, test, and enroll those found to be HIV positive in medical care. RESULTS: Health advisors interviewed 1462 persons with HIV infection during the evaluation period; these persons provided information about 1607 sexual partners. Health advisors notified 1347 (83.8%) of these partners, of whom 900 (66.8%) were HIV tested. Of partners tested, 451 (50.1%) were HIV positive, of whom 386 (85.6%) enrolled into HIV medical care. An average 3.2 index cases needed to be interviewed to identify 1 HIV case. CONCLUSIONS: HIV PS can be successfully implemented in a developing country and is highly effective in identifying persons with HIV infection and linking them to care. PMID- 24220351 TI - Criteria for the diagnosis of neurosyphilis in cerebrospinal fluid: relationships with intrathecal immunoglobulin synthesis and blood-cerebrospinal fluid barrier dysfunction. AB - BACKGROUND: The origin of cerebrospinal fluid (CSF) syphilis antibodies (intrathecal or blood-derived) is in doubt. Little is known about CSF test behavior under the condition of physiological or disturbed functioning of blood CSF barrier (BCB) and intrathecal immunoglobulin (Ig) production. METHODS: We collected 126 serum/CSF pairs from patients with serological evidence of syphilis. We explored the relationships between the established facts of intrathecal Ig synthesis and/or BCB dysfunction and the results of CSF diagnostic tests: the Treponema pallidum hemagglutination (TPHA) test, the fluorescent treponemal antibody absorption (FTA-Abs) test, the Venereal Disease Research Laboratory (VDRL) test, and white blood cell counts. We checked the criteria used either to support or refute the diagnosis of neurosyphilis. RESULTS: Reactive CSF VDRL tests, elevated CSF-white blood cell counts, and elevated CSF-TPHA titers/indices were associated with the signs of intrathecal Ig synthesis, whereas nonreactive CSF-fluorescent treponemal antibody absorption, nonreactive CSF-TPHA tests, and CSF-TPHA titers from 1:4 to 1:160 were associated with cases where the intrathecal synthesis was not detected. There were some peculiarities of the tests toward BCB dysfunction.Most of reactive CSF-VDRL test samples and CSF samples with pleocytosis were also meeting at least 1 of the CSF-TPHA titer/indices-based criteria. T. pallidum hemagglutination indices were in no better conformity with the facts of intrathecal immune response than CSF-TPHA titers. CONCLUSIONS: Our findings have shown that all the examined criteria for the diagnosis of neurosyphilis in CSF are different assessment tools of intrathecal humoral immune activity and support the hypothesis that high CSF treponemal-specific antibody titers are a consequence of inflammatory pathology of the central nervous system. PMID- 24220350 TI - HIV partner notification: possible and essential. PMID- 24220352 TI - Etiology of genital ulcer disease and association with HIV infection in Malawi. AB - BACKGROUND: The World Health Organization recommends the use of syndromic management for patients presenting with genital ulcer disease (GUD) in developing countries. However, effective treatment guidelines depend on a current country specific GUD etiological profile, which may change over time. METHODS: From 2004 to 2006, we conducted a cross-sectional analysis of baseline data from patients presenting with GUD at a reference STI clinic in Lilongwe, Malawi. Participants were enrolled in a randomized clinical trial of acyclovir added to syndromic management and followed up for up to 28 days. Serologies for HIV (using parallel rapid tests), herpes simplex virus type 2 (HSV-2; using Focus HerpeSelect IgG2 ELISA [Focus Technologies, Cypress Hill, CA]), and syphilis (rapid plasma reagin confirmed by Treponema pallidum hemagglutination) were determined, with plasma HIV-1 RNA and CD4 count in HIV-positive patients. Genital ulcer disease etiology was determined by real-time multiplex polymerase chain reaction from lesional swabs. RESULTS: A total of 422 patients with GUD (313 men; 74%) were enrolled. Overall seroprevalence of HIV-1, HSV-2, and syphilis were 61%, 72%, and 5%, respectively. Ulcer etiology was available for 398 patients and showed the following: HSV-2, 67%; Haemophilus ducreyi, 15%; T. pallidum, 6%; lymphogranuloma venereum, 6%; mixed infections, 14%, and no etiology, 20%. Most HSV-2 ulcers were recurrent (75%). Among all patients with HSV-2, HIV prevalence was high (67%) and HIV seroprevalence was higher among patients with recurrent HSV-2 compared with patients with first-episode HSV-2 (78% vs. 39%, P < 0.001). CONCLUSIONS: Herpes simplex virus type 2 ulcers are highly prevalent in this symptomatic population and strongly associated with HIV. Unlike most locations in sub-Saharan Africa, H. ducreyi remains prevalent in this population and requires periodic monitoring and an appropriate treatment regimen. PMID- 24220353 TI - Fast-track services for all? The preferences of Chinese-, Korean-, and Thai speaking women attending a sexual health service. AB - BACKGROUND: Sydney Sexual Health Centre (SSHC) Xpress clinic has significantly reduced the length of stay and waiting time for clients at SSHC but is currently only available to clients who can read and understand a high level of English. This reduces access for culturally and linguistically diverse (CALD) clients. This study sought to determine the acceptability of 4 proposed components of an express clinic model among CALD clients: computer-assisted self-interview (CASI), self-collection of swabs/urine specimens, not having a physical examination, and consultation with a health promotion officer rather than with a clinician. Differences in acceptability based on language group, new or return client status, sex worker status, clinic visited status, and age were analyzed. METHODS: A cross-sectional, anonymous questionnaire was offered to all female Chinese, Thai, and Korean clients attending SSHC between March and November 2012. Multivariate regression and Pearson chi statistical analyses were conducted using STATA 12 software. RESULTS: A total of 366 questionnaires were returned from 149 Thai, 145 Chinese, and 72 Korean participants. After multivariate analysis, the only predictor of willingness to use an express model of service provision was language group: overall, 67% Thai (odds ratio, 3.74: confidence interval [CI], 2.03-6.89; P < 0.01) and 64% Korean (odds ratio, 3.58; CI, 1.77-7.25, P < 0.01) said that they would use it compared with 35% Chinese. Age, history of sex work, new or returning clients, and general or language clinic attendance did not impact on choices. Within the preference for individual components of the model, more Thai women were happy with using a health promotion officer (43.2%) than Chinese (14.1%) or Korean (8.5%) (P < 0.001); no groups were happy with forfeiting a physical examination; Thai (48.6%) and Korean (40.9%) were happier with self-swabbing than Chinese women (23.9%, P < 0.001); and more Thai were happy to use a CASI (44.2%) than Chinese (12%) or Korean (11.1%; P < 0.001). CONCLUSIONS: This research shows that the components of an express model used at SSHC are not favorable to our CALD client base. Despite a CALD express clinic having the potential to reduce waiting times, most clients did not favor reduced waiting time over being physically examined or using a CASI. PMID- 24220354 TI - Sex networking of young men who have sex with men in densely connected saunas in Hong Kong. AB - BACKGROUND: Some men who have sex with men (MSM) meet and have sex with male partners at gay saunas, the connections between which are little explored for designing HIV prevention measures. This study aims to describe the network configuration of gay saunas and explore its relationship with risk behavior of MSM in the respective sauna communities, in the city of Hong Kong. METHODS: Using venue-based sampling, 205 MSM were recruited in 8 saunas in July 2011 for a cross sectional anonymous questionnaire survey. A network of saunas was constructed based on the proportion of clients shared between them. Core saunas with higher intensity of linkages were delineated from core-periphery analysis. Men who have sex with men in core saunas were compared with those in peripheral ones in terms of their demographics and risk behavioral profiles. RESULTS: Eight core saunas were differentiated from a highly connected sauna network, consisting of 13 saunas with a diameter of 2. Men who have sex with men visiting core saunas were more likely to be younger and users of the Internet for sex networking (odds ratio, 5.43; 95% confidence interval, 1.84-16.01). On average, they visited 1.7 saunas and had 2.6 sauna partners over a 1-month period, which were both significantly higher than those for MSM in peripheral saunas. However, there was no association between having unprotected anal sex and visiting core saunas. Sauna affiliation patterns were age dependent and geographically related. CONCLUSIONS: Saunas were not homogeneously connected with each other. Prioritization may be considered so that public health interventions can be targeted at saunas in denser networks. An assortative mixing in age among MSM in sauna community informs planning for client-specific venue-based prevention programs. PMID- 24220355 TI - Use of the dye stain assay and ultraviolet light test for assessing vaginal insertion of placebo-filled applicators before and after sex. AB - BACKGROUND: Applicator dye staining and ultraviolet (UV) light have been used in trials to measure adherence, but not in the setting of before and after sex gel dosing (BAT-24). This study was designed to determine if semen or presex gel dosing impacts the sensitivity and specificity of a dye stain assay (DSA) for measuring vaginal insertion of placebo-filled applicators with BAT-24 dosing. METHODS: Healthy monogamous couples received Microlax-type applicators (Tectubes, Astorp, Sweden) filled with hydroxyethylcelluose placebo gel. Women were instructed to vaginally insert 1 dose of gel before and a second dose after sex and to return applicators within 48 hours after sex. Applicators were stained to detect semen, followed by UV then DSA, and scored by 2 readers. Positive and negative controls were randomly included in applicator batches. RESULTS: Fifteen couples completed the study. Each woman returned at least 6 applicators over a 30 day period. The sensitivity for insertion of postsex applicators was higher for UV (97%) compared with DSA (90%), and the specificity was similar (>=96%). For presex applicators, the sensitivity and specificity were higher for DSA (100%) compared with UV testing (87% sensitivity, 96% specificity). Among returned postsex applicators, 95% tested positive by UV compared with 87% by DSA. Agreement between readers was significantly better on the presex applicators for DSA than for UV, and for postsex readings, agreement was less than half that for UV, although the results were not statistically significant. CONCLUSIONS: Applicator tests are feasible for measuring adherence in trials with gel dosing before and after sex. PMID- 24220356 TI - Bacterial vaginosis-associated bacteria in men: association of Leptotrichia/Sneathia spp. with nongonococcal urethritis. AB - BACKGROUND: Approximately 45% of nongonococcal urethritis cases have no identified etiology. Novel bacteria recently associated with bacterial vaginosis (BV) in women may be involved. We evaluated the association of idiopathic nongonococcal urethritis and 5 newly described BV-associated bacteria (BVAB). METHODS: Heterosexual men 16 years or older attending a sexually transmitted disease clinic in Seattle, Washington, from May 2007 to July 2011 and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum-biovar2 were eligible. Cases had urethral discharge or 5 or more polymorphonuclear leukocytes per high-power field in urethral exudates. Controls had no urethral discharge and less than 5 polymorphonuclear leukocytes per high-power field. Urine was tested for Atopobium spp., BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed polymerase chain reaction. RESULTS: Cases (n = 157) and controls (n = 102) were of similar age, education, and income, and most were white. Leptotrichia/Sneathia spp. was significantly associated with urethritis (24/157 [15.3%] vs. 6/102 [5.9%], P = 0.03). BVAB-2 was more common in cases than in controls (7/157 [4.5%] vs. 1/102 [1.0%], P = 0.15), and BVAB-3 (n = 2) and Megasphaera spp. (n = 1) were only detected in men with urethritis, but these bacteria were found only in men who also had Leptotrichia/Sneathia spp. Atopobium spp. was not associated with urethritis. The quantity of bacteria did not differ between cases and controls. Among treated cases, doxycycline was more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia spp. (9/10 vs. 7/12, P = 0.16) and BVAB-2 (3/3 vs. 0/3, P = 0.10). CONCLUSIONS: Leptotrichia/Sneathia spp. may be urethral pathogens or contribute to a pathogenic microbiota that can also include BVAB-2, BVAB-3, and Megasphaera spp. Doxycycline may be more effective than azithromycin against these newly identified bacteria. PMID- 24220357 TI - Evaluation of 3 approaches for assessing adherence to vaginal gel application in clinical trials. AB - BACKGROUND: Accurate measurement of adherence to product use is an ongoing challenge in microbicide trials. METHODS: We compared adherence estimates using 2 applicator tests (a dye stain assay [DSA] and an ultraviolet light assay [UVA]), the Wisebag (an applicator container that electronically tracks container openings), and self-reported adherence (ability, frequency, and percent missed doses). Healthy, HIV-negative, nonpregnant US women aged 23 to 45 years received a Wisebag and 32 applicators filled with placebo gel were instructed to insert 1 applicator daily for 30 days, returned the Wisebag and all applicators, and completed an exit interview. Emptied applicators were tested by UVA and then DSA, and scored by 2 blinded readers. Positive and negative controls were randomly included in applicator batches. RESULTS: Among 42 women enrolled, 39 completed the study. Both DSA and UVA yielded similar sensitivity (97% and 95%) and specificity (79% and 79%). Two participants had fully inoperable Wisebags, and 9 had partially inoperable Wisebags. The proportion of participants considered to have high adherence (>=80%) varied: 43% (Wisebag), 46% (UVA), 49% (DSA), and 62% to 82% (self-reports). For estimating high adherence, Wisebag had a sensitivity of 76% (95% confidence interval, 50%-93%) and a specificity of 85% (95% confidence interval, 62%-97%) compared with DSA. Although 28% of participants reported forgetting to open the Wisebag daily, 59% said that it helped them remember gel use. CONCLUSIONS: Dye stain assay and UVA performed similarly. Compared with these tests, self-reports overestimated and Wisebag underestimated adherence. Although Wisebag may encourage gel use, the applicator tests currently seem more useful for measuring use in clinical trials. PMID- 24220358 TI - Characteristics and risk of syphilis diagnosis among HIV-infected male cohort: a population-based study in Houston, Texas. AB - BACKGROUND: This population-based study assessed the characteristics, timing, and risk of syphilis diagnoses among HIV-infected males in Houston, Texas. METHODS: A retrospective cohort of males newly diagnosed as having HIV between January 2000 and December 2002 was constructed using HIV surveillance data. These individuals were cross-referenced to sexually transmitted disease surveillance data to ascertain early syphilis diagnoses for the subsequent 10 years. Multivariable Cox regression was used to identify risk factors for syphilis diagnosis while controlling for the effects of covariates. RESULTS: Approximately 6% of the HIV infected male cohort received early syphilis diagnoses during a 10-year period. Of these comorbid individuals, 40.8% received an incident syphilis diagnosis 5 years or more after their HIV diagnosis. Men who have sex with men (MSM) transmission risk was associated with significantly increased hazard of having a syphilis diagnosis in multivariable analysis (adjusted hazard ratio [HR] of a syphilis diagnosis, 5.24; 95% confidence interval, 3.41-8.05). Compared with men who were older than 40 years at HIV diagnosis, those 13 to 19 years old were 4.06 (2.18-7.55) times more likely to obtain a syphilis diagnosis. The HRs of having an HIV-syphilis comorbidity decreased as age increased. Compared with whites, non Hispanic African Americans had 1.59 (1.11-2.26) times increased risk of having a subsequent syphilis diagnosis. Risk-stratified HRs showed that MSM had an increased risk of contracting syphilis in all race/ethnicity and age groups. CONCLUSIONS: This study suggests that HIV-positive African Americans, youth, and MSM had increased risk of having a subsequent syphilis diagnosis. Targeting these groups with STI prevention messaging may be beneficial to reducing comorbidity. PMID- 24220359 TI - Are wives of gay men becoming the next target of HIV infection in China? PMID- 24220360 TI - Evidence of higher levels of testosterone during the velvet period in muntjac than in other cervids. AB - Previous studies have shown that despite having a clear seasonal fluctuation in fecal testosterone concentration, the significantly lower testosterone levels found in velvet stags of the nonseasonal breeder muntjac (Muntiacus sp.) apparently did not stop their spermatogenesis as in other deer species. In the present study, in vitro cultivated Leydig cells isolated from adult stags of three native deer species of Taiwan were treated with androstenedione, with or without adding human chorionic gonadotropin. Results showed that, unlike the two seasonal breeders, sika deer (Cervus nippon) and sambar deer (Rusa unicolor), Leydig cells of velvet muntjac had no dramatic reduction in or even maintained the full capability of their testosterone productivity compared with the hard antlered stage. The decrease in fecal testosterone level observed earlier in muntjac during the velvet period was probably due to a reduction of number of Leydig cells. These results support the hypothesis that testosterone production in muntjac during its velvet period might never be low enough to trigger the quiescent phase of the reproduction cycle. PMID- 24220361 TI - The new system of shorter porcine oocyte in vitro maturation (18 hours) using >=8 mm follicles derived from cumulus-oocyte complexes. AB - Despite recent efforts to improve in vitro maturation (IVM) systems for porcine oocytes, developmental competence of in vitro-matured oocytes is still suboptimal compared with those matured in vivo. In this study, we compared oocytes obtained from large (>=8 mm; LF) and medium (3-7 mm; MF) sized follicles in terms of nuclear maturation, intracellular glutathione and reactive oxygen species levels, gene expression, and embryo developmental competence after IVM. In the control group, cumulus-oocyte complexes (COCs) were aspirated from MF and matured for 22 hours with hormones and subsequently matured for 18 to 20 hours without hormones at 39 degrees C, 5% CO2 in vitro. In the LF group, COCs were obtained from follicles larger than 8 mm and were subjected to IVM for only 18 hours. The ovaries have LF were averagely obtained with 1.7% per day during 2012 and it was significantly higher in the winter season. The results of the nuclear stage assessment of the COCs from the LFs are as follows: before IVM (0 hours); germinal vesicle stage (15.2%), metaphase I (MI) stage (55.4%), anaphase and telophase I stages (15.8%), and metaphase II (MII) stage (13.6%). After 6 hours IVM; germinal vesicle (4.2%), MI (43.6%), anaphase and telophase I (9.4%), and MII (42.8%). After 18-hour IVM; MI (9.7%) and MII (90.3%). Oocytes from LF showed a significant (P < 0.001) increase in intracellular glutathione (1.41 vs. 1.00) and decrease in reactive oxygen species (0.8 vs. 1.0) levels compared with the control. The cumulus cells derived from LFs showed lower (P < 0.1) mRNA expression of COX-2 and TNFAIP6, and higher (P < 0.1) mRNA expression of PCNA and Nrf2 compared with the control group-derived cumulus cells. After parthenogenetic activation, in vitro fertilization and somatic cell nuclear transfer (SCNT) using matured oocytes from LFs, the embryo development was significantly improved (greater blastocyst formation rates and total cell numbers in blastocysts) compared with the control group. In conclusion, oocytes from LFs require only 18 hours to complete oocyte maturation in vitro and their developmental competence is significantly greater than those obtained from MFs. Although their numbers are limited, oocytes from LFs might offer an alternative source for the efficient production of transgenic pigs using SCNT. PMID- 24220362 TI - Characterization of follicle and CL development in beef heifers using high resolution three-dimensional ultrasonography. AB - The aim was to characterize dominant follicle (DF) and CL development through the estrous cycle of cattle using three-dimensional (3D) ultrasonography while making a comparison with conventional two-dimensional (2D) B-mode ultrasound (US) and to relate the measures taken to systemic concentrations of steroid hormones and gonadotropins. After synchronization of estrus, the ovaries of crossbred beef heifers (N = 5) were assessed using daily US with a GE Voluson i US scanner until the end of the first follicle wave, then every other day until emergence of the final (ovulatory) wave, when daily US resumed until ovulation. Follicle and CL growth were recorded and mapped. Measures of diameter (2D) and volume (3D) of the DF from the first and ovulatory waves of the cycles; and CL development were captured and stored for further analysis. Blood flow to the DF and CL were assessed using 3D power Doppler US measuring vascularization index (VI; %), vascularization flow index (0/100) and flow index (0/100). Jugular blood samples were collected every 24 hours for progesterone from the first estrus until the second ovulation. Concentrations of estradiol (E2) and follicle stimulating hormone (FSH) were measured every 8 hours from estrus to second follicle wave emergence; then, E2 only was measured from final follicle wave emergence until ovulation. Data were analyzed using PROC MIXED and PROC REG in SAS. Dominant follicle blood flow tended to decrease during follicle wave emergence and DF VI increased (P < 0.05) 24 hours before ovulation after peak E2. Measures of the DF and CL volume (3D) were highly predictive of 2D diameter measures throughout the cycle (P < 0.0001). Predictive values (r(2)) for day of wave emergence and day from ovulation were similar for 2D and 3D measures; however, 2D measures had higher repeatability when compared with 3D measures. There was no relationship between CL VI and progesterone early in the cycle (r(2) = 0.12; P = 0.1); however, there was a strong positive relationship approaching ovulation (r(2) = 0.77; P < 0.0001). In conclusion, 3D power Doppler measures of blood flow appears to be representative of vascular changes in the DF and CL throughout the estrous cycle. However, the extra time required to acquire and analyze a 3D image and the relatively little additional information obtained over that achievable with 2D imaging in terms of follicle and CL development might preclude its widespread use other than for detailed research purposes. PMID- 24220363 TI - Progesterone exposure of seasonally anoestrous ewes alters the expression of angiogenic growth factors in preovulatory follicles. AB - Small-dose, multiple injections of GnRH given to seasonally anoestrous ewes induce final stages of the preovulatory follicle development, but result in an high incidence of defective CL unless animals are primed with progesterone, which completely eliminates luteal dysfunction. Progesterone priming upregulates luteal vascularization; however, its effect on follicular angiogenesis is poorly understood. This study tested the hypothesis that progesterone priming of seasonally anoestrous ewes treated with dose multiple injections of GnRH eliminates defective luteal function by altering the expression of vascular endothelial growth factor (VEGF), VEGF receptor-2, angiopoietin (ANG)-1, ANG-2, and TIE-2 during early and late preovulatory follicle development. Ten seasonally anoestrous ewes were given 20 mg of progesterone im 3 days before the start of GnRH treatment; 10 other animals served as controls. Intravenous injections of 500 ng GnRH were given to all animals every 2 hours for 28 hours, followed at 30 hours with a 300-MUg GnRH bolus injection to synchronize the preovulatory LH surge. Ovaries were collected at 24 and 46 hours after the start of GnRH treatment. Small (2-2.5 mm) and large (>2.5 mm) follicles were analyzed for protein and mRNA expression of the angiogenic factors using immunohistochemistry and in situ hybridization assays. Progesterone priming did not have an influence on angiogenic factor levels in small follicles. However, progesterone-primed animals showed significantly (P <= 0.05) higher levels of VEGF, VEGFR-2, ANG-1, and ANG-2 in large follicles compared with nonprimed ones. These data suggest that progesterone priming alters the expression of angiogenic factors in large preovulatory follicles, ensuring adequate luteal development and function. PMID- 24220364 TI - The new era of scientific information systems change; or just a natural evolution in the works. PMID- 24220365 TI - Accuracy of upper jaw positioning with intermediate splint fabrication after virtual planning in bimaxillary orthognathic surgery. AB - The purpose of the study is to present and discuss a workflow regarding computer assisted surgical planning for bimaxillary surgery and intermediate splint fabrication. This study describes a protocol starting from wax bite registration to fabrication of the necessary intermediate splint. The procedure is a proof of concept to replace not only the model surgery but also facebow registration and transfer from facebow to articulator. Three different modalities were utilized to obtain this goal: cone beam computed tomography (CBCT), optical dental scanning, and 3-dimensional printing. A universal registration block was designed to register the optical scan of the wax bite to the CBCT data set. Integration of the wax bite avoided problems related to artifacts caused by dental fillings in the occlusal plane of the CBCT scan. Fifteen patients underwent bimaxillary orthognathic surgery. The printed intermediate splint was used during the operation for each patient. A postoperative CBCT scan was taken and registered to the preoperative CBCT scan. The difference between the planned and the actual bony surgical movement at the edge of the upper central incisor was 0.50 +/- 0.22 mm in sagittal, 0.57 +/- 0.35 mm in vertical, and 0.38 +/- 0.35 mm in horizontal direction (midlines). There was no significant difference between the planned and the actual surgical movement in 3 dimensions: sagittal (P = 0.10), vertical (P = 0.69), and horizontal (P = 0.83). In conclusion, under clinical circumstances, the accuracy of the designed intermediate splint satisfied the requirements for bimaxillary surgery. PMID- 24220366 TI - Comparison of orbital volume obtained by tomography and rapid prototyping. AB - PURPOSE: This study aims to compare orbital volume obtained by helical tomography and rapid prototyping. METHODS: The study sample was composed of 6 helical tomography scans. Eleven healthy orbits were identified to have their volumes measured. The volumetric analysis with the helical tomography utilized the same protocol developed by the Plastic Surgery Unit of the Federal University of Parana. From the CT images, 11 prototypes were created, and their respective volumes were analyzed in 2 ways: using software by SolidWorks and by direct analysis, when the prototype was filled with saline solution. For statistical analysis, the results of the volumes of the 11 orbits were considered independent. RESULTS: The average orbital volume measurements obtained by the method of Ono et al was 20.51 cm, the average obtained by the SolidWorks program was 20.64 cm, and the average measured using the prototype method was 21.81 cm. The 3 methods demonstrated a strong correlation between the measurements. The right and left orbits of each patient had similar volumes. CONCLUSIONS: The tomographic method for the analysis of orbital volume using the Ono protocol yielded consistent values, and by combining this method with rapid prototyping, both reliability validations of results were enhanced. PMID- 24220367 TI - Rainbow graft: a technique for the replacement of the lower lateral cartilages, improvement of tip projection, and correction of external nasal valve dysfunction. AB - Revision rhinoplasties are extremely difficult to perform even for the surgeons mastering nasal surgery. In fact, they must be skilled at adapting surgical strategies to the anatomical changes induced by primary rhinoplasty.We herein describe an original technique using an auricular cartilage graft after 6 revision rhinoplasties.The aforementioned graft succeeded in improving tip support, correct external nasal valve dysfunction and alar pinch, and providing tip definition, projection, and ptosis.In our opinion, rainbow graft is a safe approach in case of severe nasal structural deficiencies, improving both the functional and esthetic results in revision rhinoplasties. PMID- 24220368 TI - Augmented corticotomy-assisted presurgical orthodontics of class III malocclusions: a cephalometric and cone-beam computed tomography study. AB - OBJECTIVE: The purpose of this study was to evaluate mandibular incisor decompensation and the surrounding periodontal status with augmented corticotomy assisted presurgical orthodontics of class III patients. METHODS: Fifty-six surgical class III patients were enrolled in this study, 26 of whom chose augmented corticotomy-assisted presurgical orthodontics (G1), and 30 chose conventional procedures (G2). Cone-beam computed tomography images and lateral cephalograms were obtained from each patient before and after presurgical orthodontics. Measurements of variables were compared using Student t tests and separate variance estimation t tests. RESULTS: The amount of mandibular incisor decompensation and the increase in labial alveolar bone thickness in G1 were greater than those in G2 during presurgical orthodontics (P < 0.001), however, root resorption (P < 0.001), the decrease in lingual alveolar bone thickness (P < 0.001), and vertical alveolar bone loss on both labial (P < 0.05) and lingual sides (P < 0.001) were less in G1 than in G2. CONCLUSIONS: Sufficient mandibular incisor decompensation and better periodontal preservation were achieved with augmented corticotomy-assisted presurgical orthodontics for class III patients compared with traditional procedures. PMID- 24220369 TI - Fractures of the pediatric zygoma: a review of the clinical trends, management strategies, and outcomes associated with zygomatic fractures in children. AB - Fractures of the pediatric zygoma are uncommon and are often associated with high impact trauma, as evidenced by the relatively increased prevalence of concomitant injuries observed in these patients. Despite advances in the prevention, diagnosis, and management of pediatric craniofacial injuries, data regarding zygomatic fractures in children remain poorly established. The diagnosis of zygomatic disruption is more difficult in children and requires the maintenance of a high index of suspicion on behalf of the surgeon. Early recognition and implementation of appropriate therapy are critical and depend on the acquisition of a thorough history and physical examination as well as the accurate interpretation of computed tomographic imaging. Options for management depend on fracture severity and can range from observation or closed reduction in nondisplaced or only minimally displaced fractures, to open reduction and internal fixation in fractures that are comminuted or severely displaced. Currently, there is a lack of level I evidence evaluating the long-term consequences associated with pediatric zygomatic fractures and their management. A review of the epidemiology, clinical characteristics, diagnosis, and management of pediatric zygomatic fractures is essential for optimizing function and aesthetic outcomes in children who sustain these injuries. PMID- 24220370 TI - The impact of a parent liaison at a major craniofacial center. AB - The psychosocial impact of craniofacial disfigurement affects both the developing child and his/her family. The Facial Reconstruction Center at the Children's Hospital of Philadelphia has employed a Parent Liaison (PL) to provide psychosocial support to families and has been an invaluable resource in this regard. We hypothesize that a PL impacts the overall outcome of the surgery by building trust between the parents and medical institution, and increasing satisfaction. An anonymous satisfaction survey was sent to families of craniofacial patients treated between January 1976 and June 2012. All patients who had undergone at least 1 craniofacial procedure had addresses on file and were included in this study. Statistical analyses were performed using the Mann Whitney U test.During the study, 441 surveys were mailed to families meeting the inclusion criteria. A total of 151 families returned completed surveys (34.2%), and 121 surveys were included for analysis (27.4%). In rating overall satisfaction, families who met with the PL had statistically higher scores than those who had not (P = 0.0011). Parents who met with the PL preoperatively reported greater satisfaction in time spent answering questions (P = 0.0029) and the perception that questions were adequately answered (P = 0.0039). No statistical difference was observed in postoperative preparedness between families that did and did not meet the PL. The results demonstrate that the PL is beneficial in the education, experience, and satisfaction of families treated at a large Craniofacial Center. The PL complements the surgeon's treatment of the physical by adding psychosocial support. PMID- 24220371 TI - Scintigraphic and histopathologic evaluation of combined bone grafts. AB - OBJECTIVES: We aimed to assess various bone grafts on bone formation using bone scintigraphy and histology, especially the first study that evaluated the demineralized bone matrix (DBM) + tricalcium phosphate (TCP) + hyaluronic acid (HA) combination. MATERIALS AND METHODS: A total of 44 pieces in groups of autogenous bone graft, TCP, DBM, DBM + TCP combination, and DBM + TCP + HA combination were applied to parietal bones of 24 New Zealand rabbits. Bone scintigraphies of the rabbits were performed at 2, 6, and 12 weeks. The uptake ratios were compared for the different types of grafts. In addition, in 2, 6, and 12 weeks, the graft areas were taken from the sacrificed rabbits and examined histologically. RESULTS: In the 2-week evaluation, DBM + TCP combination and DBM + TCP + HA combination had more osteoblastic activity accumulation than the TCP and DBM groups. These findings supported that the DBM + TCP combination group showed new bone formation earlier in the histopathological evaluation. The DBM + TCP + HA combination had more uptake than the TCP and DBM groups on bone scintigraphy at 2 weeks, and this uptake ratio decreased in the following weeks. It was thought that the increased uptake in DBM + TCP + HA combination at 2 weeks was due to severe inflammation seen in the histopathological evaluation. CONCLUSION: The DBM + TCP + HA combination should not be used for graft repair, although it was thought to be a good combination in the early weeks. PMID- 24220372 TI - Is there an effect of obstructive sleep apnea syndrome on oxidative stress and inflammatory parameters in patients with craniofacial anomalies? AB - The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exhibits oxidative stress and inflammation in patients who have a congenital, craniofacial anomaly.This prospective, cross-sectional cohort study included ambulant sleep study data to asses OSAS in patients with syndromic craniosynostosis and Treacher Collins syndrome. Laboratory analyses were performed including malondialdehyde, tumor necrosis factor alpha (TNF-alpha), interleukin 6, and high-sensitivity C-reactive protein.Forty-eight patients were included; 11 were adults; 37 were children. The patients' body mass indexes were normal, with a median (SD) of 0.7 (-1.82 to 2.48) in children and 20.5 (15.2 29.4) in adults. Obstructive sleep apnea syndrome was diagnosed in 23 of 48 patients. It was mild (median obstructive apnea-hypopnea index [oAHI], 2.3; oxygenation-desaturation index [ODI], 0.9) in 16 patients and moderate/severe in 7 patients (median oAHI, 10.8; ODI, 5.0). Neither oxidative stress nor inflammation had a correlation with the oAHI and ODI. Only TNF-alpha was found significantly higher in both the OSAS and non-OSAS groups compared with the reference values (median, 15.1 pg/mL and 12.3 pg/mL versus 4.05 [0.0-8.1 pg/mL], P < 0.001 and P < 0.001, respectively).Based on our findings we conclude that (mainly mild) OSAS, oxidative stress, as well as high-sensitivity C-reactive protein and interleukin 6 levels are not abnormal in the day time in a population of nonobese patients with a craniofacial anomaly. The increased level of TNF alpha cannot be explained by OSAS. Future research should focus on mapping chronobiologic changes for further interpretation of the results. PMID- 24220373 TI - Prefabricated bone flap: an experimental study comparing deep-frozen and lyophilized-demineralized allogenic bones and tissue expression of transforming growth factor beta. AB - BACKGROUND: Extensive bone defects are still a challenge for reconstructive surgery. Allogenic bones can be an alternative with no donor area morbidity and unlimited amount of tissue. Better results can be achieved after allogenic bone preparation and adding a vascular supply, which can be done along with flap prefabrication. The purpose of this study was to evaluate demineralized/lyophilized and deep-frozen allogenic bones used for flap prefabrication and the tissue expression of transforming growth factor beta (TGF beta) in these bone fragments. METHODS: Fifty-six Wistar rat bone diaphyses were prepared and distributed in 4 groups: demineralized/lyophilized (experimental group 1 and control group 2) and deep freezing (experimental group 3 and control group 4). Two bone segments (one of each group) were implanted in rats to prefabricate flaps using superficial epigastric vessels (experimental groups) or only transferred as grafts (control groups). These fragments remained in their respective inguinal regions until the death that occurred at 2, 4, and 6 weeks after the operation. Semiquantitative histologic (tetracycline marking, cortical resorption, number of giant cells, and vascularization) and histomorphometrical quantitative (osteoid thickness, cortical thickness, and fibrosis thickness) analyses were performed. Transforming growth factor beta immunohistochemistry staining was also performed. RESULTS: Group 1 fragments presented an osteoid matrix on their external surface in all periods. Cartilage formation and mineralization areas were also noticed. These findings were not observed in group 3 fragments. Group 1 had more mineralization and double tetracycline marks, which were almost not seen in group 3. Cortical resorption and the number of giant cells were greater in group 3 in all periods. Vascularization and fibrosis thickness were similar in both experimental groups. Group 1 had more intense TGF beta staining within 2 weeks of study. Nevertheless, from 4 weeks onward, group 3 presented statistically significant stronger staining. CONCLUSIONS: Although there are some differences between the preparation methods of allogenic bone, it is possible to prefabricate flaps with demineralized/lyophilized and deep-frozen bones. PMID- 24220374 TI - Facial fractures of the upper craniofacial skeleton predict mortality and occult intracranial injury after blunt trauma: an analysis. AB - PURPOSE: The aim of this article was to assess how regional facial fracture patterns predict mortality and occult intracranial injury after blunt trauma. METHODS: Retrospective chart review was performed for blunt-mechanism craniofacial fracture patients who presented to an urban trauma center from 1998 to 2010. Fractures were confirmed by author review of computed tomographic imaging and then grouped into 1 of 5 patterns of regional involvement representing all possible permutations of facial-third injury. Mortality and the presence of occult intracranial injury, defined as those occurring in patients at low risk at presentation for head injury by Canadian CT Head Rule criteria, were evaluated. Relative risk estimates were obtained using multivariable regression. RESULTS: Of 4540 patients identified, 338 (7.4%) died, and 171 (8.1%) had intracranial injury despite normal Glasgow Coma Scale at presentation. Cumulative mortality reached 18.8% for isolated upper face fractures, compared with 6.9% and 4.0% for middle and lower face fractures (P < 0.001), respectively. Upper face fractures were independently associated with 4.06-, 3.46-, and 3.59-fold increased risk of death for the following fracture patterns: isolated upper, combined upper, panfacial, respectively (P < 0.001). Patients who were at low risk for head injury remained 4 to 6 times more likely to suffer an occult intracranial injury if they had involvement of the upper face. CONCLUSIONS: The association between facial fractures, intracranial injury, and death varies by regional involvement, with increasing insult in those with upper face fractures. Cognizance of the increased risk for intracranial injury in patients with upper face fractures may supplement existing triage tools and should increase suspicion for underlying or impending neuropathology, regardless of clinical picture at presentation. PMID- 24220375 TI - Silk fibroin and 4-hexylresorcinol incorporation membrane for guided bone regeneration. AB - The objective of this study was to demonstrate that a silk fibroin (SF) and 4 hexylresorcinol (4-HR) incorporation membrane could be used for a guided bone regeneration technique. Fourier transform infrared measurements were obtained to determine change of physical property of SF membrane by 4-HR incorporation. Two peri-implant defects, 3.0 * 5.0 mm (width * length), were prepared on the lateral side of the implant hole in the tibia of New Zealand white rabbits (n = 8). The peri-implant defect was left unfilled in the control group. Silk fibroin + 4-HR membrane was applied to the peri-implant defect in the experimental group. The 8 animals were killed at 8 weeks after implantation. Subsequently, removal torque test and histomorphometric evaluation were done. Fourier transform infrared spectroscopy showed no specific chemical interaction between 4-HR and SF. In the histomorphometric analysis, the mean bone regeneration was 18.3 +/- 1.9 mm(2) in the experimental group and 9.3 +/- 0.9 mm(2) in the control group (P = 0.004). In conclusion, the SF and 4-HR incorporation membrane successfully regenerated bone in the rabbit tibia peri-implant bone defect model. PMID- 24220376 TI - The effect of duration of merocel in glove finger with tetracaine solution on septoplasty morbidity. AB - OBJECTIVE: We aimed to decrease the postseptoplasty morbidities depending on nasal packing by using Merocel within glove finger moistened with tetracaine 0.25% solution. STUDY DESIGN: The study was designed as a randomized prospective study. SETTING: A university hospital in Turkey. SUBJECTS AND METHODS: Our study consisted of 80 patients who underwent septoplasty. The Merocel nasal tampon within glove finger was inserted after surgery in the study group and removed after 24 or 48 hours. Merocel was moistened with tetracaine 0.25% solution after insertion into the nasal cavity and just before removal. The morbidities and normal breathing time were recorded and compared with those of the control group. RESULTS: The postseptoplasty morbidities were significantly decreased in the study group compared with those in the control group. The morbidities were also improved after removal of tampons after 24 hours compared with 48 hours. However, the normal breathing time was prolonged when the nasal tampons were removed after 24 hours. CONCLUSIONS: The glove finger provides comfortable removal of nasal packing. The Merocel tampons might be safely removed just after 24 hours postoperatively without any complication. PMID- 24220377 TI - Glass particle injury to the maxillofacial region. AB - A retrospective study was carried out wherein 10 patients with glass particle injury reporting to the Department of Oral and Maxillofacial Surgery between January 2011 and March 2012 were included. Preoperative photographs and radiographs were done, and detailed surgical planning followed. Ninety percent of the patients were males with involvement of the right side of the face in 70% of the cases. The most common presenting symptom was patient sensation, which was the reason for availing delayed treatment in 70% of cases, followed by delayed or fibrotic healing (20%) and pain (10%). The diagnosis and planning were done based on computed tomographic scan (50% cases), plain radiographs (30%), needle as tactile aid (10%), and palpation (10%). Eighty percent of cases were diagnosed/presented late. The timely diagnosis of glass particle injuries requires a high degree of suspicion for the same. A systematic diagnosis and treatment planning for such injuries can minimize the morbidity and prevent such injuries from being overlooked at time of primary injury. PMID- 24220378 TI - Juvenile idiopathic/rheumatoid arthritis and orthognatic surgery without mandibular osteotomies in the remittent phase. AB - BACKGROUND: Orthognathic treatment of patients with juvenile idiopathic/rheumatoid arthritis is still controversial. Mandibular procedures may result in relapse and further condylar resorption and pain. Maxillary osteotomies and genioplasty may be effective for the correction of malocclusion and for aesthetics. PATIENTS AND METHODS: Five patients with juvenile idiopathic/rheumatoid arthritis with severe temporomandibular joint (TMJ) involvement underwent orthognathic surgery with a simultaneous Le Fort I osteotomy and advancement genioplasty. The age of the patients at the time of surgery ranged between 17 and 29 years (mean, 21.75 years). The patients were under follow-up for a minimum of 8 months after surgery, and measurements were performed using Dolphin 3D imaging. RESULTS: All 5 patients have an improved occlusion and improved facial aesthetics. The mean mandible rotation advancement was 5.6 mm (range, 4 to 7 mm). The mean posteroanterior face height ratio (S-Go/N Me) after surgery was 63.9 (range, 62.9 to 65.8). No exacerbation of the juvenile rheumatoid arthritis was encountered as a result of the surgical procedure. CONCLUSIONS: Le Fort I osteotomy with impaction and advancement genioplasty are effective procedures for occlusal and aesthetic correction of juvenile idiopathic/rheumatoid patients. Mandibular procedures may evoke further condylar resorption with pain and functional impairment of the TMJ. PMID- 24220379 TI - Effect of changes in divine proportion on esthetic perception of smile in frontal view. AB - OBJECTIVES: In orthognathic surgery, the surgeon is capable of creating new dimensions to the patient's face. Because a beautiful smile could be related to the divine proportion, the purpose of the current study was to evaluate the changes in the perception of smile after approximating some components of smile to the divine proportion orthodontically or surgically. MATERIAL AND METHODS: Ten 20- to 25-year-old women with pleasant smiles and no obvious malocclusions participated in this study. Five standard photographs were taken from each participant in a posed smile, and the most natural one was selected and scanned into black and white pictures. Ten anthropometric landmarks were detected on each image and 10 ratios including Labial inferioris (Li)/right chelion (RCh)-right antegonion (RAgo), subnasale (Sn)-Li/left chelion (LCh)-left antegonion (LAgo), RCh-RAgo/labial superioris (Ls)-Li, LCh-LAgo/Ls-Li, Ch-Ch/Ls-Li,stomion (St) Sn/St-Li, the maxillary central incisor width/maxillary centralincisor height, Ls right cuspid (RCus)/RCh-RCus, Ls-left cuspid (LCus)/LCh-LCus, and LCus-RCus/Ch-Ch were measured on each picture. The numerators or denominators of the mentioned ratios were then changed in a way that mentioned the divine proportion (1/1.618) was approximated. All the 110 pictures were evaluated by 40 judges in 2 sessions using a visual analog scale. Intraclass correlation coefficient was also calculated (single measure, 0.644; F = 26.27; P < 0.001). The level of significance for this study was P = 0.05. The tests used to analyze the data were general linear model, the Friedman, and Wilcoxon tests. RESULTS: This study showed that LCus-RCus/Ch-Ch, Ls-Lcus/LCh-Lcus, and Ls-RCus/RCh-RCus (with mean scores of 64.2, 57.2, and 56.1, respectively) had the most positive effects on the esthetic perception of smile. However, RCh-RAgo/Ls-Li with a mean score of 29.1 and LCh-LAgo/Ls-Li with a mean score of 24.5 had the mostnegative effects. There were significant differences among the variables with each other except for A0 to J0 and A6 to J6 (F = 450.6; P = 0.001). CONCLUSIONS: Approximating the ratio RCus-LCus/Ch-Ch to the divine proportion may definitely help in achieving a more pleasant smile. On the next level, altering the ratios Ls-LCus/LCh-LCus and Ls-RCus/RCh-RCus could also play a role in making a beautiful smile. PMID- 24220380 TI - Investigation of middle ear pressure changes during prone position under general anesthesia without using nitrous oxide. AB - PURPOSE: The effects of different body positions on the middle ear were reported in several studies, but there are no data about the effects on patients under general anesthesia. The aim of this study is to determine the effect of prone position on middle ear pressure (MEP) during general anesthesia without using nitrous oxide. METHODS: Twenty patients under general anesthesia during prone position were included in the study. The performed anesthesia method was the same for all patients. Remifentanil was used for analgesia instead of nitrous oxide. MEPs were measured 5 times with a middle ear analyzer: before induction (BI), after intubation (AI), after turned to the prone position (PP1), at the end of the prone position (PP2), and after returned to the supine position (SP). Duration of prone position was also recorded. RESULTS: Of the 20 patients were 11 women and 9 men with a 49 +/- 13 mean age. BI-AI, AI-PP1, PP1-PP2, and PP2-SP comparisons of both MEPs were statistically significant (P < 0.0001). Right mean MEPs were BI, -1 +/- 23 daPa; AI, 41 +/- 51 daPa; PP1, 124 +/- 76 daPa; PP2, 152 +/- 59 daPa; and SP, 63 +/- 29 daPa; whereas left mean MEPs were BI, -24 +/- 55 daPa; AI, 28 +/- 34 daPa; PP1, 132 +/- 67 daPa; PP2, 162 +/- 48 daPa; and SP, 70 +/- 89 daPa. Significant increases were detected at the start and continuation of the prone position. The mean duration of prone position was 98 +/- 51 per minute. CONCLUSIONS: The significant MEP increases during the prone position under general anesthesia depend on a number of reasons. Among them are inhaler agents, pressure changes in mucosal blood vessels due to venous congestion, and the mastoid bone volume. Further researches are required to determine and explain the mechanisms of increase in MEP during prone position. PMID- 24220381 TI - Facial paralysis and mediastinitis due to odontogenic infection and poor prognosis. AB - Cervical necrotizing fasciitis (CNF) is a rare, rapidly advancing infection that involves the skin, the subcutaneous fibrofatty tissue, as well as the superficial and deep fascia and can cause life-threatening complications. The most frequent initiating factors in the head and neck region are a primary odontogenic infection, a peritonsillar infection, as well as posttraumatic or iatrogenic skin and mucosal injuries. Necrotizing fasciitis (NF) can expand within hours, and the reported mortality rate is up to 75% with delay interference. If the patients have any risk factors, poor prognosis can be seen. In this study, 1 patient with CNF with a history of peritonsillar infection and 2 patients with CNF who had a history of odontogenic infection with spreading to the temporal region and the mediastinum were described, with information of the literature and a clinical experience that was gained from 5 patients with NF who were seen at our clinic in the recent year, despite the fact that CNF was not seen up to last year. None of the patients had any risk factors. One of them had a worse clinical state with ascending infection to the temporal region, cranial nerve paralysis, and descending necrotizing mediastinitis, but he recovered from NF. After the oral intake began, dyspnea due to aspiration was seen and he died because of sepsis and multiorgan dysfunction. We aimed to attract attention to the importance of dental pathologies and increased mortality in a healthy patient. PMID- 24220382 TI - Camel bite injury to the maxillofacial region: unusual cause and uncommon location. AB - Animal bite injuries are prevalent worldwide, but the causative animal and the spectrum of injuries are dependent on the kind of animals cohabitating with the human population. Camel bites as a cause are relatively rare. Camels are particularly aggressive, especially during the mating season, when conflicts between the males occasionally lead to dangerous fights resulting in the death of one or both of the combatants. We present a case of camel bite injury to the maxillofacial region inducing an uncommon fracture and the management of both soft and hard tissue injuries, especially addressing the literature for this uncommon bite injury. Because of the unique mode of injury, the ramus was horizontally fractured and displaced. The fracture was also compound because of the deep intraoral bite wounds. The ramal fracture itself is a rare entity. The issue of primary or delayed closure in such cases is addressed. PMID- 24220383 TI - Functional and histologic changes in the lacrimal gland after botulinum toxin injection. AB - PURPOSE: The purpose of this study was to evaluate changes in tear volume, epidermal growth factor (EGF), and histology of the rabbit lacrimal gland after intraglandular application of botulinum toxin. METHODS: Ten New Zealand rabbits were separated into 3 groups. Eight rabbits received botulinum toxin injection (2.5 U per 0.1 mL) into the right lacrimal gland and saline injection (0.1 mL) into the left lacrimal gland as a sham control. Two rabbits were untreated to serve as normal controls. Tear volume was measured using cotton thread every 2 weeks, and 4 rabbits were killed after 2 and 4 weeks. The lacrimal glands were surgically excised and sectioned or lysed for gene expression analysis. Epidermal growth factor expression and concentration were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay; morphometric and histologic analyses were performed. RESULTS: The rabbits that were killed 2 weeks after the injection showed decreased tear volume and increased EGF expression and concentration, but differences were not statistically significant. The rabbits that were killed 4 weeks after the injection exhibited similar results. When all 8 rabbits were considered, we detected a significant decrease in tear volume and increased EGF expression and concentration (P = 0.012, P = 0.011, and P = 0.012, respectively). The EGF level was not significantly correlated with the tear volume. There were no prominent histologic changes between the glands, and the lumen versus fibrosis ratio in the interlobular ducts showed no statistically significant difference. CONCLUSIONS: The use of botulinum toxin in patients with epiphora is effective, safe, and repeatable because it reduces tear volume and increases the EGF level to prevent corneal damage while causing no histologic changes. PMID- 24220384 TI - Basicranial venous anomalies associated with complex nonsyndromic craniosynostosis in a child. AB - We report the radiological findings of severe bilateral jugular foraminal stenosis along with anomalous basicranial venous drainage in a child with a history of complex nonsyndromic craniosynostosis. CT with 3D reconstructions and MR venography revealed that the lateral sinuses were draining transosseously through several markedly enlarged emissary veins. The main route of transverse and sigmoid sinus drainage was through large mastoid emissaries to the deep cervical veins. There was additional drainage of these mastoid emissaries into the vertebral and paravertebral plexuses as well as into venous collaterals which subsequently reconstituted the internal jugular veins. Basicranial venous anomalies are common among children with complex craniosynostosis, and although they may not resemble intracranial vascular outflow deficiencies, they can pose significant surgical risks. This case emphasizes the need for proper clinical assessment and documentation of anomalous basicranial venous anatomy to facilitate management of complex craniosynostosis patients. PMID- 24220385 TI - Treatment effects of distal movement of lower arch with miniscrews in the retromolar area compared with miniscrews in the posterior area of the maxillary. AB - OBJECTIVE: The aim of this study was to compare the effects of group distal movement of lower teeth obtained with the aid of direct usage of miniscrews in the retromolar area and indirect usage of miniscrews in the posterior area of the maxillary. METHODS: Nineteen patients with mild-to-moderate class III malocclusion (4 males and 15 females) were divided into 2 groups. Ten patients (2 males and 8 females; mean age, 20.7 +/- 2.5 years) in group 1 were treated by miniscrews in the retromolar area. Nine patients (2 males and 7 females; mean age, 21.5 +/- 3.7 years) in group 2 were treated by miniscrews in the posterior area of the maxillary. Lateral cephalometric headfilms were taken at the beginning of treatment and after distal movement of mandibular dentition for the evaluation of the treatment changes. RESULTS: In group 1, the crown and root apex of lower first molars were moved distally by 3.4 mm and 1.2 mm with distal tipping of 8.7 degrees and intruded by 0.7 mm. In group 2, the crown and root apex of lower first molars were moved distally by 3.3 mm (P = 0.8976, P > 0.05) and 0.2 mm (P = 0.0124, P < 0.05) with distal tipping of 10.7 degrees (P = 0.0467, P < 0.05) and extruded by 0.2 mm (P = 0.0124, P < 0.05). Retraction of the mandibular arch lasted 6.31 +/- 1.45 months for group 1 and 7.61 +/- 1.46 months for group 2. CONCLUSIONS: Direct usage of miniscrews in the retromolar area took less time and more bodily movement to retract the lower arch without cooperation of the patients and was a better choice for the patients with potential temporomandibular joint disorders problems. PMID- 24220386 TI - Systematic analysis of clinical outcomes of anterior maxillary and mandibular subapical osteotomy with preoperative modeling in the treatment of bimaxillary protrusion. AB - The purpose of this study was to determine the changes in teeth and hard tissues after preoperative modeling and bimaxillary anterior subapical osteotomy for the treatment of bimaxillary protrusion. Cephalometric analysis was used to evaluate the aesthetic effects and occlusal relationships obtained. The subjects included 19 women and 1 man (aged 19-41 years; average, 29 years) with bimaxillary protrusion who underwent anterior subapical osteotomy of both the maxilla and mandible, with simultaneous genioplasty, if required. Based on a preoperative computer-aided manufacturing/design-assisted and model surgical design and an occlusal guide plate, new occlusal relationships were established for the patients. In addition, the preoperative and postoperative cephalometric radiographs were systematically analyzed. In all patients, the surgical incisions underwent primary healing, with no infection or osteonecrosis. Significant differences were observed in the preoperative and postoperative values of all hard tissue and teeth parameters, except for SGn-FH degrees and Co-MP. The most obvious significant differences were seen in L1-OP degrees , Id-Pog-Go degrees , IIA degrees , U1E-Apog, L1E-Apog, U1E-NA, and L1-NA degrees (P < 0.001). Postoperative follow-up lasted for 12 to 36 months. All patients eventually achieved normal jaw relationships, tooth arch forms, and Spee curves. No evident irregularities of teeth arrangement or abnormal occlusal relationships were observed. All patients were satisfied with their postoperative facial appearance, except for 1 patient, who underwent repeat surgery because of relapse. With the use of a precise preoperative model surgical design, orthognathic surgery, a simple and time-saving technique, can be used to correct bimaxillary protrusion with satisfactory postoperative occlusal relationship and facial aesthetic appearance and minimal postoperative complications. PMID- 24220387 TI - Depressor muscle division through a subbrow excision for the improvement of brow ptosis. AB - The aim of this study was to introduce a technique of dividing forehead depressor muscles with a subbrow excision for improvement of brow ptosis or redundant upper eyelid skin and glabella wrinkles. Upper incisions were designed at the lower limit of the eyebrow with a lateral extension along the eyebrow curvature. After measuring the redundant upper eyelid skin, the excess skin was excised. The orbital part of the orbicularis oculi muscle was identified and split longitudinally. The forehead depressor muscles (depressor supercilii, oblique and transverse head of corrugator, and medial part of orbicularis oculi) in the brow fat pad were identified and avulsed. In the patients who have a lowered brow, the brow was elevated and fixed to the underlying periosteum about 1 cm above the superior orbital rim after subgaleal dissection. During the dissection, the supraorbital nerve was preserved. Preaponeurotic fat was transferred and sutured between the cut stumps of the corrugator and procerus. The 78 patients (19 men, 60 women; age range, 41-72 years [mean, 52.0 +/- 7.1 years]) were operated on. The follow-up periods ranged from 3 to 48 months. Preoperative and postoperative photographs were taken, and the following evaluations were conducted by 1 surgeon via a Likert scale (1 = not improved, 2 = slightly improved, 3 = somewhat improved, 4 = much improved, 5 = markedly improved). The mean score for improvement of the glabella frowns in contraction was 3.7 +/- 1.6. The mean score for the improvement of the glabella frowns in relaxation was 4.1 +/- 1.3. The mean score for improvement of drooping eyelids was 4.7 +/- 0.5. The mean score for the improvement of forehead wrinkles was 4.8 +/- 0.7. We improved brow ptosis, redundant upper eyelid skin, and glabella wrinkles simultaneously using a subbrow excision and depressor muscle division while preserving the superficial branch of the supraorbital nerve. PMID- 24220388 TI - The transconjunctival approach a minimally invasive approach to various kinds of retrobulbar tumors. AB - PURPOSE: Orbital tumors, particularly those within the retrobulbar space, were approached by maxillofacial, ophthalmic, and neurological surgeons. Less traumatic approaches in this functionally and cosmetically important region are desirable. We describe another method to remove orbital tumor in the retrobulbar space by a transconjunctival approach with lateral canthotomy and transient extraocular muscle severing without lateral orbitotomy. METHODS: We report 5 retrobulbar tumors operated with a transconjunctival approach, 2 of which were intraconal. Contrast-enhanced computed tomography and magnetic resonance imaging scans were used to determine precise location of the retrobulbar tumor. RESULTS: Retrobulbar tumors could be removed successfully through a transconjunctival approach. Three pleomorphic adenomas, 1 carvenous hemangioma, and 1 pseudotumor were the pathologic findings encountered. These patients were free from visible scars, proptosis, and any other noticeable complications at last follow-up, 6 months after surgery. CONCLUSIONS: The transconjunctival approach, which involves lateral canthotomy and transient extraocular muscle severing without lateral orbitotomy, is an unconventional procedure for retrobulbar tumor and results in a successful outcome. The indications for this approach depend on the size, location, and nature of the tumor. In this regard, contrast-enhanced computed tomography and magnetic resonance imaging scans give useful information for planning operative strategy. PMID- 24220389 TI - Transoral robotic surgery for atypical carcinoid tumor of the larynx. AB - In recent years, transoral robotic surgery has been introduced as an efficient and a reliable method for excision of selected oral cavity, tongue base, and supraglottic tumors in otolaryngology. In this case report, a 39-year-old woman with a history of hoarseness and dysphagia for approximately 6 months is presented. The patient was diagnosed with atypical carcinoid tumor on the laryngeal aspect of the epiglottis, and excision of the tumor was performed through transoral robotic surgery using the robotic da Vinci surgical system, a 0 degree three-dimensional endoscope, 5-mm microinstruments compatible with the da Vinci robot, and a Feyh-Kastenbauer/Weinstein-O'Malley retractor. The mass was removed completely, and no complications occurred. The patient recovered without a need for tracheotomy. Findings of the 1-year clinical follow-up revealed no locoregional recurrence or distant metastasis. This case shows, once again, that transoral robotic surgery could be used safely and effectively regardless of pathologic diagnosis in the supraglottic region tumors. PMID- 24220390 TI - Maxillary mucocele with proptosis and visual impairment: a late complication of Le Fort III distraction. AB - Maxillary mucoceles are a relatively rare entity especially following surgical procedures involving osteotomies of the maxilla. The etiology of maxillary mucoceles has been ascribed to facial trauma (fractures), sinus surgery, and chronic inflammatory diseases or infections. Mucoceles can follow injury to the sinus mucosa and/or sinus outflow tract with a resulting expansile cystic mass. The clinical presentation ranges from swelling, pain, a palpable mass, proptosis, enophthalmos, and diplopia. The treatment involves either open or endoscopic incision and drainage of the cyst, mucosal resection, and an antrostomy for drainage.We report the case of a patient with Pfeiffer syndrome who underwent Le Fort III distraction osteogenesis and developed a symptomatic mucocele 15 years postoperatively. PMID- 24220391 TI - Laser-assisted indocyanine green imaging to assess perfusion of scalp closure in an infant. AB - The current treatment of craniosynostosis is open surgical excision of the prematurely fused suture and cranial vault remodeling. Due to the change in skull morphology and the increase in volume, some tension on the skin flaps is noted with closure. Although complete wound breakdown is rare, it can be a devastating complication. We present our experience with the use of the SPY imaging system (Lifecell Corporation, Branchburg, NJ, USA) to visualize and record blood flow within the flaps of a 1-year-old patient with anterior plagiocephaly. Intraoperative indocyanine green angiography has the potential to be a significant advantage in such cases, providing a safe and objective method to assess intraoperative scalp perfusion, allowing the surgeon to take additional measures to ameliorate any ischemic problems. PMID- 24220392 TI - Efficacy of hyaluronic acid injections in patients with osteoarthritis of the temporomandibular joint. A comparative study. AB - The aim of the present study was to report the 1-year therapeutic outcome of intra-articular injections of high-molecular-weight hyaluronic acid (HA) without arthrocentesis in a group of 25 patients with osteoarthritis (OA) of the temporomandibular joint (TMJ). The results were compared with those of a group of 10 patients with OA of the TMJ, treated with nonsteroidal anti-inflammatory drugs.Twenty-five patients (group A) underwent a cycle of 5 injections of HA into the TMJ. Ten patients (group B) underwent a therapy with nonsteroidal anti inflammatory drugs for 1 month. The follow-up assessments after the end of treatment were at 1, 3, 6, and 12 months.Regarding the first follow-up (1 month), statistical analysis for all clinical parameters showed no significant differences (ie, beneficial effect for 2 groups) between groups A and B (P > 0.001). Significant statistical differences (ie, encouraging effect for group A) for all clinical parameters were recorded 1 year after the end of treatment between groups A and B (P < 0.001).A cycle of 5 intra-articular injections of HA without arthrocentesis for patients with OA of the TMJ is considered successful at 1-year follow-up period. PMID- 24220393 TI - Free fibula flap: assessment of quality of life of patients with head and neck cancer who have had defects reconstructed. AB - This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers. PMID- 24220394 TI - A novel method to determine the potential rotational axis of the mandible during virtual three-dimensional orthognathic surgery. AB - During virtual three-dimensional orthognathic surgery in cases where an overlap or penetrability occurs between the 2 jaws due to the repositioning of the maxillary segment, it is necessary to establish a vertical opening of the mandible to obtain a relatively good relationship with the maxillary segment for the fabrication of an intermediate occlusal splint. However, there are few reports that address the precise definition of the rotational axis of the mandible during virtual surgery. Here, we present the idea that the mandible's movement during virtual three-dimensional orthognathic surgery is similar to hinge movement in vivo and developed a method for locating the geometric center of the three-dimensional condyle using Hypermesh software combined with Mimics software. Subsequently, we defined the rotational axis of the mandible based on the located geometric centers of the bilateral condyles, and the mandible was then rotated around the defined axis from the retruded contact position to mimic the hinge movement. Preliminary results indicated that the presented method could approximately mimic the hinge movement of the mandible with a relatively high accuracy in a three-dimensional environment, which may improve the accuracy of virtual intermediate occlusal splint. PMID- 24220395 TI - Management of extensive frontal cranioplasty defects. AB - Cranioplasty is a medical technique to correct cranial bone defects. Depending on the size and location of the defect, a bone substitute can be used to replace the missing bone. Frontal bone defects are important to patients in terms of cosmetics because they are visible. Advances in computer design allow the production of customized implants with improved cosmetic and functional results. This report describes hybrid optimization of three-dimensional technological methods along with traditional methods toward the manufacture of deep-buried titanium implants, restoring frontal skull defects for 4 patients. A three dimensional model was produced from the computed tomographic scan data of 3 patients using an in-house three-dimensional printer. A new approach was followed in treating the fourth patient. The defect was restored using preoperative scan before cranioplasty. These data were transported digitally into the defect skull to recreate the bone contour required, and a three-dimensional model was produced from the "new" digital model using the three-dimensional printer. Defect areas of the patients were large and measured 101.21 * 123.35 (vertical * horizontal) in average (mm). Conventional wax-up of the defect was carried to restore normal conformity. A titanium sheet (0.5 mm) was swaged into the desired shape; however, convexity of the defect area makes titanium swaging challenging, especially at the deep lateral undercuts. Making side flanges at reasonable lengths made it easy to swage without creasing. Three-dimensional models aided to produce accurately fitting plates. Finally, the sequential method of using both digital and manual procedures is a low-cost, reliable, accurate, and reproducible method. PMID- 24220396 TI - Video analysis of the biomechanics of a bicycle accident resulting in significant facial fractures. AB - INTRODUCTION: This study aimed to use video analysis techniques to determine the velocity, impact force, angle of impact, and impulse to fracture involved in a video-recorded bicycle accident resulting in facial fractures. Computed tomographic images of the resulting facial injury are presented for correlation with data and calculations. To our knowledge, such an analysis of an actual recorded trauma has not been reported in the literature. MATERIALS AND METHODS: A video recording of the accident was split into frames and analyzed using an image editing program. Measurements of velocity and angle of impact were obtained from this analysis, and the force of impact and impulse were calculated using the inverse dynamic method with connected rigid body segments. These results were then correlated with the actual fracture pattern found on computed tomographic imaging of the subject's face. RESULTS: There was an impact velocity of 6.25 m/s, impact angles of 14 and 6.3 degrees of neck extension and axial rotation, respectively, an impact force of 1910.4 N, and an impulse to fracture of 47.8 Ns. These physical parameters resulted in clinically significant bilateral mid-facial Le Fort II and III pattern fractures. DISCUSSION: These data confer further understanding of the biomechanics of bicycle-related accidents by correlating an actual clinical outcome with the kinematic and dynamic parameters involved in the accident itself and yielding a concrete evidence of the velocity, force, and impulse necessary to cause clinically significant facial trauma. These findings can aid in the design of protective equipment for bicycle riders to help avoid this type of injury. PMID- 24220397 TI - Superior sagittal sinus thrombosis as a treatment complication of nonsyndromic Kleeblattschadel. AB - A patient with nonsyndromic Kleeblattschadel, who underwent a craniotomy involving a constricting calvarial ring and frontal calvarial remodeling, developed a superior sagittal sinus thrombosis. The superior sagittal sinus venous outflow was obstructed as a consequence of the rapid brain expansion, along with a conflict of a remaining posterior bone crest. A successful second operation was performed to remove the posterior bone crest and facilitate the venous outflow. Meticulous preoperative planning should be carried out before addressing this complex craniofacial deformity. PMID- 24220398 TI - Delayed reduction of a displaced zygomatic arch fracture by external traction. AB - An easy and useful method designed for the reduction of delayed and displaced zygomatic arch fractures used by the treatment of a 33-year-old female patient is presented. PMID- 24220399 TI - Use of high-frequency ultrasound guidance for intraoperative zygomatic arch fracture reduction. AB - Zygomatic arch fractures are common facial fractures; the management depends on the extent of the injury, the displacement of the bone, and coronoid impingement. For fractures without a need for fixation, an intraoral approach, known as Keen, or a temporal hairline approach, known as Gillies, can be used. However, without direct visualization of the fracture line, there is a risk for inadequate reduction. We have therefore begun to use ultrasound assistance to confirm proper reduction. We believe that intraoperative ultrasound guidance can be used to guide the surgeon toward the most precise fracture reduction and present 3 examples from our practice. We recommend the use of ultrasound in the reduction of zygomatic arch fractures. PMID- 24220400 TI - Indirect cerebral revascularization with a temporoparietal fascial flap in pediatric moyamoya patients: a novel technique and review of current surgical options. AB - Moyamoya syndrome is a progressive occlusive disease of the cerebral vessels. There are a variety of surgical treatments directed at revascularizing the ischemic brain in pediatric moyamoya disease. Many reports of varying success with both direct and indirect type of procedures can be found in medical literature. We present a novel technique, encephalo-TPF-synangiosis (ETS) with a pedicled bone flap, for indirect moyamoya revascularization in pediatric patients. A three-quarters osteoplastic temporal craniotomy was created. A pedicled temporoparietal fascial flap was passed intracranially through the temporalis muscle and placed into contact with the pial surface. The bone flap was the reaffixed to the skull. We performed 8 ETS in 6 patients. This is a well vascularized, highly reliable method that offers broad-based surface area for revascularization. We also offer a composite overview of current surgical indirect revascularization techniques. PMID- 24220401 TI - Infraorbital nerve posttraumatic deficit and displaced zygomatic fractures: a double-center study. AB - Typical associated signs and symptoms of displaced zygomatic fractures include lack of zygoma projection, diplopia, and sensory disturbances of the infraorbital nerve (ION). The aim of this article was to assess eventual associations between ION sensory disturbances and zygomatic fractures patterns. This study is based on 2 databases that have continuously recorded patients hospitalized with maxillofacial fractures in 2 Departments of Maxillofacial Surgery in Amsterdam, The Netherlands, and Turin, Italy between 2001 and 2010. The following data for patients surgically treated for displaced zygomatic fractures were considered: gender, age, site and severity of facial fractures, etiology, and presenting symptoms. Statistically significant associations were found between ION sensory disturbances and assaults (P = 0.007) and sport accidents (P = 0.00003), as well as between ION sensory disturbances and isolated zygomatic fractures (P = 0.000002) and between ION sensory disturbances and diplopia (P = 0.00009).The severity of injury and the absorption of middle-energy and high-energy forces by the zygomatic complex only were associated with ION sensory disturbances. The etiology and severity of the injury as well as the presence of associated symptoms should be thoroughly investigated when a zygomatic fracture is suspected. PMID- 24220402 TI - Horner syndrome due to vertebral artery stenosis. AB - The author reports a rare case of Horner syndrome in a patient who resulted from stenosis of the vertebral artery after blunt trauma. A 31-year-old man was transferred to our department for evaluation of left medial orbital wall and nasal bone fractures. Five days ago, he was hospitalized due to multiple second to fourth rib fractures of the right chest following blunt trauma of the face, neck, and chest. Surgery was performed. Ten days later, he complained of drooping of the right eyelid. Physical examination revealed a discrete miosis and ptosis with normal levator function in the right eye. A workup for Horner syndrome was performed. Magnetic resonance angiography of the head and neck revealed a stenosis of the distal part of the right vertebral artery without the abnormality of carotid artery. He wore a cervical collar and underwent anticoagulation. However, Horner syndrome was not resolved over the next 12 months. Acute traumatic Horner syndrome may be associated with vertebral artery dissection in which the possibility of life-threatening injury can be masked. PMID- 24220403 TI - Transosseous fixation of pediatric displaced mandibular fractures with polyglactin resorbable suture--a simplified technique. AB - Management of pediatric mandibular fractures presents a unique challenge to surgeons in terms of its numerous variations compared to adults. Both conservative and open methods have been advocated with their obvious limitations and complications. However, conservative modalities may not be possible in grossly displaced fractures, which necessitate the open method of fixation. We present a novel and simplified technique of transosseous fixation of displaced pediatric mandibular fractures with polyglactin resorbable suture, which provides adequate stability without any interference with tooth buds and which is easy to master. PMID- 24220404 TI - A new facial artery free-style perforator flap and conchal cartilage graft for one-step reconstruction of the alar defects. AB - The nose is the most commonly affected area by basal and squamous skin carcinomas of the head and neck area (D'Arpa et al. J Plast Reconstr Aesthet Surg. 2009, 62:36-42). The nasolabial flap is a very well known local flap that provides excellent color and texture matches. However, its major drawback is that it requires a 2-stage procedure to restore an adequate nasal cheek groove (Karsidag et al. J Craniofac Surg. 2010;21:1887-1889). In the perforator flaps, there are numerous studies that describe flaps whose vascular supply depend on perforators from the fascial artery.We planned to harvest a perforator flap around the medial cheek area, which included one cutaneous perforator from the facial artery. Free style facial artery perforator flaps and auricular conchal cartilage framework were performed in 9 patients who have alar defect due to malignancies.From September 2010 to December 2011, the free-style facial perforator artery flap was performed in 9 patients at the Plastic and Reconstructive Surgery Department of the Ankara Numune Training and Research Hospital, Turkey. The whole flap was used to reconstruct the whole alar unit, which includes cartilaginous tissues.Our aim is to define a one-stage reconstruction technique with a perforator-based flap. Our flap is supplied by a perforating branch of the facial artery. We develop this method because of its reliable vascularization, that is, the possibility of performing one-stage technique with sensation preservation.In conclusion, we strongly recommend one-stage reconstruction in any kind of alar region defect with this versatile facial perforator flap. PMID- 24220405 TI - Microscope-assisted reconstruction of canalicular laceration using Mini-Monoka. AB - A canalicular laceration is the most common injury of the lacrimal drainage system and can result from direct or indirect injury to the canalicular system. If the wounds are not managed properly, they can lead to scarring, stenosis, and inflammation, which may lead to symptomatic epiphora. We successfully reconstructed canalicular lacerations using Mini-Monoka tubes (FCI Ophthalmics, Marshfield Hills, MA) under microscopic magnification.We treated 14 patients for canalicular lacerations at the Soonchunhyang University Bucheon Hospital between August 2009 and October 2012. All patients underwent placement of a Mini-Monoka tube and a mucosal canalicular anastomosis microscopically to reconstruct monocanalicular lacerations. The tubes were removed at 6 to 8 months postoperatively, and follow-up was 8 to 12 months. No complications related to the Mini-Monoka tube, such as punctual plug migration, eye irritation, inflammation, granuloma formation, or erosion, occurred during the follow-up period.The goal of reconstructing a lacerated canaliculus is accurate approximation of the injured end of the canaliculus to facilitate mucosal healing and to prevent a canalicular obstruction. We believe that microscopic canalicular reconstruction with a Mini-Monoka tube is a safe, reliable, and straightforward method with fewer complications and is more effective for preventing iatrogenic injury in the unaffected canaliculus and minimizing patient discomfort. PMID- 24220406 TI - The double scalpel flap: a new technique for the closure of circular skin defects. AB - Reconstruction needs to be designed attentively to obtain a functional and a good aesthetic consequence for closing skin defects. Numerous local flaps have been defined to conceal skin defects. However, new techniques are still required, especially for circular type of skin defects.This study describes a new technique that has been well defined to repair the circular type of skin defects. The technique basically uses extra skin relaxation provided with 2 opposing flaps' rotation maneuver in favor of the defect closure. The objective of this technique is for the flaps to start from one border of the defect and extend just to the other border, not invading beyond the defect borders. This enables us to apply the procedure on defects that are close to important anatomical structures because it is sufficient to use only the opposing 2 sides of the defect for its closure.With this method, 2 opposing flaps that resemble the tip of a scalpel were rotated to the existing circular defect; and by suturing these 2 flaps at the midline, the defect was closed. This technique was applied to 17 patients between the ages of 48 and 83 years. Defect sizes were between 2.5 * 2.5 and 5 * 5 cm.With the use of opposing flaps designed narrower than half-width of the defect, a tension-free closure could be achieved on both the donor and the recipient site. No flap necrosis was detected on any patients. After a mean follow-up of 11 months (3-26 months), it was realized that a good aesthetic appearance could be achieved in all the patients about 2 to 3 months postoperatively. PMID- 24220407 TI - A learning curve of endoscopic transsphenoidal surgery for pituitary adenoma. AB - Experience is an important point in the effectiveness of the surgical procedure and in the reduction of complications in pituitary surgery. Endoscopic pituitary surgery differs from microscopic surgery because it requires a steep learning curve for endoscopic skills. In this study, we investigated the learning curve of endoscopic transsphenoidal pituitary surgery in our department. Endoscopic transsphenoidal operations were performed on 80 patients, who were retrospectively examined and grouped as the early and late experience groups to evaluate the learning curve. The patients' characteristics, gross total resection, endocrinological cure, visual field improvement, duration of surgery, postoperative hospital stay, and complications were noted. After examining our patients of the 2 groups of period, our experience showed that as the effectiveness of endoscopic surgery increases, the duration of surgery and postoperative hospital stay decrease. In this study, we identified a learning curve in endoscopic pituitary surgery. PMID- 24220408 TI - A patient with severe maxillary gingival exposure treated with combined compression osteogenesis of the anterior alveolar bone and conventional Le Fort I osteotomy. AB - Excessive gingival exposure at the maxillary anterior region during not only smiling (a gummy face) but also at rest creates both functional and aesthetic problems for patients. We herein introduce a unique treatment procedure for mandibular retrognathia with a gummy face. This procedure combines conventional Le Fort I osteotomy and following corticotomy at the anterior region of the maxilla. Subsequently, the anterior segment is continuously compressed (compression osteogenesis) in a posterior-superior direction until it reaches an ideal position. This procedure appears to safely and adequately resolve both the aesthetic and functional complaints associated with patients with a gummy face. PMID- 24220409 TI - Distal transsylvian-traninsular approach for the putaminal hypertensive hemorrhages: surgical experience and technical note. AB - BACKGROUND: Up to now, no systemic studies about the surgical approaches and microsurgical techniques of distal transsylvian-transinsular approach to putaminal hypertensive intracranial hemorrhages (PHHs) were reported. METHODS: A retrospective analysis was performed on 68 consecutive patients with PHH who underwent surgical treatment at the Department of the affiliated Bayi Brain Hospital, the Military General Hospital of Beijing PLA, from May 2009 to December 2011. RESULTS: By using transsylvian-transinsular approach, near-complete (>90%) evacuation was achieved in 51 cases (75%). Glasgow Coma Scale scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 6 months was 95.6% (65/68), including 60.3% (41/68) with good function (Glasgow Outcome Scale [GOS] score, 4-5), 19.1% (13/68) with disability (GOS score, 3), and 16.2% (11/68) in a vegetative state (GOS score, 2). The mortality rate (GOS score, 1) was 4.4% (3/68). CONCLUSIONS: Transsylvian transinsular approach is effective and minimally invasive for PHH. The opening of sylvian fissure toward the pars opercularis behind the level of anterior ascending rami could provide a more suitable angle to hematoma and the ability to treat the responsible vessels. PMID- 24220410 TI - Reverse facial artery flap to reconstruct the medium-sized defects in the middle facial region following cancer ablation. AB - This retrospective clinical study assessed the reliability of the reverse facial artery flap to reconstruct the medium-sized defects in the middle facial region following cancer ablation.Fifteen medium-sized defects were repaired with reversed facial artery flap following cancer surgery. The ages of the patients ranged from 2 to 69 years; 9 were male and 6 were female. The primary lesions included palate (5 cases), maxillary gingival (6 cases), cheek or buccal mucosa (3 case), and upper lip (1 case). The size of the skin paddle varied from 4.0 cm * 6.0 cm to 5.0 cm * 10.0 cm. Direct closure was achieved at all donor sites. Fourteen of the 15 flaps survived. No donor-site problems occurred. Two patients appeared to have temporary injury of facial nerve after operation. The follow-up period ranged from 8 to 36 months; 1 patient died as a result of local recurrence and 1 patient developed cervical recurrence.Consequently, it has been demonstrated that the reversed facial artery flap had reliable blood supply and can reliably and conveniently be used for reconstruction of the medium-sized defects, especially in the middle third of oral and maxillofacial region. PMID- 24220411 TI - "Roller coaster maneuver via lateral orbital approach" for reduction of isolated zygomatic arch fractures. AB - Numerous techniques have been reported for the reduction of zygomatic arch fractures. In this article, we aimed to describe a technique we named as "roller coaster maneuver via lateral orbital approach" to closed reduction of the isolated-type zygomatic arch fractures. Surgical outcomes of 14 patients treated with this method were outlined. PMID- 24220413 TI - Lower lateral crural reverse plasty. AB - The lateral crus plays a significant role in the aesthetic appearance of the nose. Excessive concavities of the lower lateral crura can lead to heavy aesthetic disfigurement of the nasal tip and to insufficiencies of the external nasal valve. The lateral crus of the alar cartilage may also cause a concavity of the alar rim and even collapse of the alar rim in severe cases. Surgical techniques performed on the lateral crus help to treat both functional and aesthetic deformities of the lateral nasal tip. We present a reverse plasty technique for the lateral crus, and we evaluated the advantages and disadvantages of the technique. PMID- 24220412 TI - Comparison between routine and improved decompressive craniectomy on patients with malignant cerebral artery infarction without traumatic brain injury. AB - BACKGROUND: Malignant cerebral artery infarction is one kind of ischemic stroke with high mortality. The aim of this study was to analyze comparatively the preoperative and postoperative clinical data as well as the prognostic factors in these patients who underwent improved decompressive craniectomy or routine decompressive craniectomy. METHODS: A total of 131 patients with malignant cerebral artery infarction were included during the period from January 2000 to December 2012. The patients were divided into 2 groups: the improved decompressive craniectomy group (n = 85) and the routine decompressive craniectomy group (control group) (n = 46). We reviewed the detailed information of the patients; moreover, a comparative analysis of the 2 groups based on age (<= 60 or >60 y) was performed. RESULTS: The improved decompressive craniectomy group had a significant decrease (P < 0.05) in mortality without clinical functional improvement. The patients who were treated through routine decompressive craniectomy had a higher incidence of hydrocephalus and pulmonary infection (P = 0.011 and 0.003). Moreover, younger patients usually took less resident time in the hospital than did the patients in the elderly group (P = 0.047 vs P < 0.05). Statistical results indicated that the younger patients took a better recovery than did the elderly patients. There was a significant difference between the groups A and B both in the Barthel index and the modified Rankine scale for 3 or 6 months after discharge (P < 0.05). CONCLUSIONS: In comparison with the routine decompressive craniectomy, the improved decompressive craniectomy can reduce the mortality rate and improve the neurologic outcome. However, it increases the incidence of encephalocele and pulmonary infection, which may cause secondary vital injury to patients after surgery. In addition, younger patients can gain a better further functional recovery by undergoing improved decompressive craniectomy. PMID- 24220414 TI - The application of multilobed flap designs for anatomic and functional oropharyngeal reconstructions. AB - The oropharynx has a variety of functions, such as mastication, deglutition, articulation, taste, and airway protection. Because of its many roles, recent goals in head and neck reconstruction have focused on anatomic and functional reconstructions to minimize functional deficits. Since chemoradiation has earned a good reputation in the management of head and neck cancer, the manifestation of oropharyngeal defects has changed. Although we could not control the anatomic defects that were known to be related to the oropharyngeal functions, we hypothesized that optimizing the flap designs would be helpful for minimizing the functional deficits.Two hundred fifty cases of the head and neck reconstruction using free flaps were carried out between March 2006 and December 2010, where modified flap designs were applied. Among these, 37 tongue and 15 tonsillar reconstructions were analyzed for functional outcomes. The patients were of Asian ethnic background, and the average age was 52 years, including 38 males and 17 females. The average follow-up period was 20.5 months. Based on previous studies, the flap designs were categorized into type I, unilobe; type II, bilobe; type III, trilobe; type IV, quadrilobe; type V, additional lobe for lateral and posterior pharyngeal wall; and type VI, additional lobe for tongue base. The functional outcomes of both tongue and tonsillar reconstructions were investigated.To quantify the outcome in terms of swallowing and pronunciation, we analyzed the patients' function based on the 7-scale parameter. In terms of swallowing, the tongue reconstruction group scored 5.70 on average, whereas the tonsillar reconstruction group showed an average score of 4.53. With regard to speech intelligibility, the tongue reconstruction group revealed an average score of 5.67, whereas the tonsillar reconstruction group scored 5.46 on average.Our findings indicate that specification of the flap designs is helpful for minimizing the functional deficits in head and neck reconstructions. PMID- 24220415 TI - Anterior clinoid process and the surrounding structures. AB - BACKGROUND: The anterior clinoid process (ACP) is located close to the optic nerve, internal carotid artery, ophthalmic artery, and can be easily injured in an ACP-related surgery. An anatomical study clearly defining the ACP is of great importance. In addition, computed tomographic (CT) images may be a new tool for the anatomical analysis of ACP compared with the use of a cadaver and skull study, and more data related to ACP can be measured by CT images. PURPOSE: We studied the anatomical structure of ACP and the structures surrounding it to provide information to surgeons for ACP-related surgery. METHODS: Computed tomography angiographic images of 102 individuals were reviewed. The measurement was performed on coronal, sagittal, and axis planes after multiplanar reformation. The length of ACP and the distance between apex of ACP and sagittal midline were measured in the axial plane; the classification of ACP and the occurrence rate of bone bridge were also viewed in axial plane. The thickness of ACP was measured in sagittal plane. RESULT: In Chinese population, 12.3% of the ACP is gasified, and the pneumatization of ACP has a relationship with the pneumatization of sphenoid sinus. The length and thickness of ACP are similar to that in previous studies in cadaver. The apex of ACP is relatively stationary to the C3 and C4 segments of the internal carotid artery. The occurrence rate of anterior and middle clinoid bone bridge was 7.8%; the occurrence rate of anterior and posterior clinoid bone bridge was 9.3%. CONCLUSIONS: The anatomical structure of ACP can be studied effectively in CT images. Recognizing the anatomical characteristics of the ACP and optic strut is important in decreasing the incidence of surgical complications of an anterior clinoidectomy and in the proper intraoperative management to prevent these complications. PMID- 24220416 TI - The safe zone of posterior semicircular canal resection in suboccipital retrosigmoid sinus approach for acoustic neuroma surgery. AB - The aim of the study was to find the safe zone of posterior semicircular canal resection that can avoid structure damage in suboccipital retrosigmoid sinus approach for acoustic neuroma. One hundred twenty subjects (72 male and 48 female subjects) were involved in this study anonymously. Five parameters are measured in computed tomography: L1 is the line that goes through the common bony crus and parallel to the plane that contains posterior semicircular canal at axial plane. L2 is the middle sagittal line at axial plane. A is the point of posterior wall of the internal auditory canal at the level of the common bony crus. B is the intersection point of L1 and posterior wall of auditory canal. L3 is the line that goes through the plane that contains posterior semicircular canal at coronary plane. L4 is the middle sagittal line at coronary plane. C is the common bony crus. D is the ampulla. E is the most posterior point of posterior wall of auditory canal at the plane that goes through the posterior semicircular canal. The angle between L1 and L2 was 41.76 (SD, 5.64) degrees on the right and 43.40 (SD, 5.25) degrees on the left (P = 0.003). The distance between A and B was 0.59 (SD, 0.13) cm. The angle between L3 and L4 was 16.57 (SD, 6.51) degrees on the right and 17.57 (SD, 6.98) degrees on the left (P = 0.017). The distance between C and D was 0.60 (SD, 0.05) cm. The distance between E and line CD was 0.48 (SD, 0.09). PMID- 24220417 TI - Locating of the pituitary stalk for craniopharyngioma surgery of transfrontobasal interhemispheric approach. AB - The aim of this study was to provide a relatively safe operation range for the protection of the pituitary stalk in transfrontobasal interhemispheric approach for craniopharyngioma surgery by measuring the related parameters of the pituitary stalk. Based on the whole-head magnetic resonance imaging scans of 119 healthy subjects (57 men and 62 women) anonymously, three-dimensional reconstructions were rebuilt. The results of the study are as follows: M is the common midpoint of anterior and inferior border of anterior commissure. O and P are the midpoint of the anterior border of the pituitary stalk's superior and inferior extremity, respectively. The distance between M and O (D1) was 12.42 (SD, 2.35) mm. The distance between M and P (D2) was 22.47 (SD, 2.57) mm. The length of the pituitary stalk (D3) was 10.68 (SD, 2.34) mm. The widest diameter of the pituitary stalk (D4) was 2.78 (SD, 0.50) mm. The inclination of the pituitary stalk at the coronal plane (A1) was 2.73 (SD, 2.60) degrees. Of the 119 pituitary stalks involved in this study, 14.29% were centered, 47.06% inclined to the left with the value (A1L) of 3.41 (SD, 2.58) degrees and 38.66% inclined to the right with the value (A1R) of 2.93 (SD, 2.49) degrees. The angle between MO and MP(A2) was 11.81 (SD, 4.76) degrees. No statistical difference was found between male and female subjects for all the measurements (P > 0.05). With the parameters measured in this study, we can locate the pituitary stalk by anterior commissure; thus, it is relatively safe to do the craniopharyngioma surgery through frontobasal interhemispheric approach when the pituitary stalk cannot be seen clearly because of the shelter of tumor, which will reduce both the unnecessary damage to the pituitary stalk and the probability of postoperative complications. PMID- 24220418 TI - Anthropometric comparison of painting portraits of beautiful women, femme fatales, and artists' mothers. AB - The aim of this study was to compare the painting portraits of beautiful women, femme fatales, and artists' mothers using anthropometry.Portraits of each theme were selected in modern novels, essays and picture books, and categorized portraits. A total of 52 samples were collected, including 20 beautiful women, 20 femme fatales, and 12 artists' mothers. In 5 persons, 17 anthropometric ratios including the alae-alae/zygion-zygion ratio were compared in a 15-degree oblique view and in anteroposterior view photographs, and they were proved to not differ significantly. To distinguish oblique portraits less than 15 degrees, we measured the exocanthion-stomion-exocanthion (ESE) angle in photographs of 5 volunteers. The mean +/- SD of the ESE angle was 64.52 +/- 4.87 in the 15-degree angle view and 57.68 +/- 54.09 in the 30-degree angle view. Thereafter, if the ESE angle was greater than 65 degrees, we considered the portrait to have less than a 15-degree angle and included it in the samples.The ratio did not differ significantly in 11 anthropometric proportions. However, the remaining 5 proportions were statistically significant. Beautiful women had wider noses (85% of the endocanthion-endocanthion width) than those of the femme fatale group (77%). Lips in the beautiful woman group are nicer and thicker (36% of lip's width) compared with the artists' mother group (27%). Femme fatales were relatively similar to beautiful women such as those women with nice and thick lips. However, the femme fatale group had an attractive midface ratio (36% of the total face height) that has been mentioned in the older literature, and the noses of the femme fatale group were narrower and sharper (77% of the endocanthion-endocanthion width) than those of the beautiful women (85%). The artists' mother group has a relatively narrower upper face (29% of the total face height) and thinner lips (27% of the lip width) compared with the other 2 groups (36%).Proportions from works of art are more ideal and attractive than clinically measured proportions. The ideal ratios measured from historical portraits might be useful in planning facial surgeries. PMID- 24220419 TI - The magnetic resonance imaging measurement of the hippocampal formation volume of normal Chinese adults. AB - The objective of this study was to measure the normal hippocampal formation of the adults in China and to provide data for the prevention and diagnoses of the related diseases. 3D-fSPGR sequence scanning was used in 68 cases of healthy adult brain to gain the image between lateral border of bilateral fourth ventricle and vitreous body. The image then was divided into 10 equal parts in the sagittal plane. We can trace the area of the hippocampal formation in each part and the data gained was analyzed by SPSS to calculate the volume. The calibrated normal adult average hippocampal formation volume on the right was 2649.92-2903.17 mm(3) while on the left was 2579.42-2803.27 mm(3). The male right average hippocampal formation volume was 2601.84-2986.44 mm(3) and the left was 2526.32-2886.94 mm(3). The female right average hippocampal formation volume was 2531.88-2819.06 mm(3) and the left was 2579.42-2803.27 mm(3). There was no obvious difference in various gender and age groups (P > 0.05), but there was a significant difference between bilateral hippocampal formation volume in middle aged and elderly male group whether calibrated (t = 2.892, P< 0.05) or not (t = 2.924, P < 0.05). We can conclude that the hippocampal formation volume of normal Han adults has no relation to gender and age except that the bilateral fourth ventricle volume of middle-aged and elderly men were evidently different from each other. PMID- 24220420 TI - Location and tension of the medial palpebral ligament. AB - The aim of this study was to elucidate the precise anatomic location and tension of the medial palpebral ligament (MPL). Eleven hemifaces of 10 fresh Korean adult cadavers were used in this study. Nine specimens were used for measurement of dissection and tension, and 2 were used for histologic study. Measurements of tensile strength of each part of the MPL and Horner muscle were performed using a force gauge.The MPL consisted of 2 layers in all specimens dissected. The superficial layer of the palpebral ligament (SMPL) was observed from the anterior lacrimal crest to the upper and lower tarsal plates. The deep layer of the palpebral ligament (DMPL) lay from the anterior lacrimal crest to the posterior lacrimal crest, covering the lacrimal sac. The Horner muscle was observed at the posterior lacrimal crest just lateral to the attachment of the DMPL and ran laterally to the tarsal plate deep to the SMPL. The SMPL began at 4.5 +/- 2.3 mm lateral to the nasomaxillary suture line to the upper and lower tarsal plates. Its transverse length was 9.6 +/- 1.5 mm, and vertical width was 2.4 +/- 0.7 mm, and its thickness was 4.5 +/- 2.3 mm. The transverse length of the DMPL was 3.7 +/- 0.4 mm, and its vertical width was 2.9 +/- 1.3 mm, with a thickness of 0.3 +/ 0.1 mm. The transverse length of the Horner muscle was 7.6 +/- 1.9 mm, and its vertical width was 4.06 +/- 1.5 mm, with a thickness of 0.4 +/- 0.1 mm. The tensile strength of the SMPL was 13.4 +/- 3.2 N, that of the DMPL was 4.1 +/- 1.7 N, and that for Horner muscle was 9.0 +/- 3.1 N. The tensile strength of the SMPL was significantly higher than that of the DMPL (P = 0.003).We reconfirmed that the MPL consisted of 2 layers: superficial layer and deep layer. Our results might be of use in surgeries of the medial canthi. PMID- 24220421 TI - Anatomical and morphometric analysis of accessory infraorbital foramen. AB - The aim of the present study was to analyze the anatomical and morphometric variation in shape, frequency of occurrence, direction, and position of accessory infraorbital foramen (AIOF) in relation to infraorbital foramen (IOF) in cadaveric dry skulls to minimize clinical complications and aid in surgical maneuvering in the maxillofacial region and implementing the regional block anesthesia. The IOF is an important anatomical landmark in these surgical manipulations. Because there is limited literature available on AIOF, which transmits accessory branch of the infraorbital nerve, the present study was designed. In the current study, 45 human dry skulls and 20 disarticulated maxillae have been used irrespective of sex. The other parameters included measuring the distance of AIOF from anterior nasal spine, frontomaxillary suture, infraorbital margin, IOF, and zygomaticomaxillary suture. The transverse and vertical diameter of foramen was also noted. All these measurements were taken using a digital caliper. The result of our study reveals that the presence of AIOF is more on the right side compared with the left side. Because the presence of accessory infraorbital nerve needs to be taken care of during maxillofacial surgical interventions, knowledge regarding the presence of AIOF should be taken into consideration for preoperative evaluation. PMID- 24220422 TI - The effects of pulsed electromagnetic field (PEMF) on osteoblast-like cells cultured on titanium and titanium-zirconium surfaces. AB - BACKGROUND: Commercially pure Ti, together with Ti Ni, Ti-6Al-4V, and Ti-6Al-7Nb alloys, are among the materials currently being used for this purpose. Titanium zirconium (TiZr) has been developed that allows SLActive surface modification and that has comparable or better mechanical strength and improved biocompatibility compared with existing Ti alloys. Furthermore, approaches have targeted making the implant surface more hydrophilic, as with the Straumann SLActive surface, a modification of the SLA surface. PURPOSE: The aim of this study is to evaluate the effects of pulsed electromagnetic field (PEMF) to the behavior of neonatal rat calvarial osteoblast-like cells cultured on commercially pure titanium (cpTi) and titanium-zirconium alloy (TiZr) discs with hydrophilic surface properties. MATERIALS AND METHODS: Osteoblast cells were cultured on titanium and TiZr discs, and PEMF was applied. Cell proliferation rates, cell numbers, cell viability rates, alkaline phosphatase, and midkine (MK) levels were measured at 24 and 72 hours. RESULTS: At 24 hours, the number of cells was significantly higher in the TiZr group. At 72 hours, TiZr had a significantly higher number of cells when compared to SLActive, SLActive + PEMF, and machine surface + PEMF groups. At 24 hours, cell proliferation was significantly higher in the TiZr group than SLActive and TiZr + PEMF group. At 72 hours, TiZr group had higher proliferation rate than machine surface and TiZr + PEMF. Cell proliferation in the machine surface group was lower than both SLActive + PEMF and machine surface + PEMF. MK levels of PEMF-treated groups were lower than untreated groups for 72 hours. CONCLUSIONS: Our findings conclude that TiZr surfaces are similar to cpTi surfaces in terms of biocompatibility. However, PEMF application has a higher stimulative effect on cells cultured on cpTi surfaces when compared to TiZr. PMID- 24220423 TI - The effect of carrier type on bone regeneration of demineralized bone matrix in vivo. AB - Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC. PMID- 24220424 TI - Effects of laser and ozone therapies on bone healing in the calvarial defects. AB - This study aims to analyze the effect of the low-level laser therapy (LLLT) and ozone therapy on the bone healing of critical size defect (CSD) in rat calvaria. A total of 30 Wistar male rats were used. A 5-mm-diameter trephine bur was used to create CSD on the right side of the parietal bone of each rat calvarium. Once the bone was excised, a synthetic biphasic calcium phosphate graft material was implanted to all the bone defect sites. The animals were randomly divided into 3 groups as follows: the control group (n = 10), which received no LLLT or ozone therapy; the LLLT group (n = 10), which received only LLLT (120 seconds, 3 times a week for 2 weeks); and the ozone therapy group (n = 10) (120 seconds, 3 times a week for 2 weeks). After 1 month, all the rats were killed, and the sections were examined to evaluate the presence of inflammatory infiltrate, connective tissue, and new bone formation areas. Histomorphometric analyses showed that in the LLLT and ozone groups, the new bone areas were significantly higher than in the control group (P < 0.05). In the LLLT group, higher new bone areas were found than in the ozone group (P < 0.05). This study demonstrated that both ozone and laser therapies had a positive effect on bone formation in rat calvarial defect, compared with the control group; however, ozone therapy was more effective than LLLT (808 nm; 0.1 W; 4 J/cm(2); 0.028 cm(2), continuous wave mode). PMID- 24220425 TI - Analysis of microRNA expression detected by microarray of the cerebral cortex after hypoxic-ischemic brain injury. AB - Small and noncoding microRNAs (miRNAs) are known as key regulators of biological processes such as cell differentiation and tumor generation. They are also the important mediators of posttranscriptional gene silencing in both pathogenic and pathologic aspects of hypoxic-ischemic brain injury. miRNA microarray has been considered to be a high-throughput and precise analysis tool for detecting miRNA expression profiling, and it does greatly facilitate the research of the biological function of miRNAs. To investigate the changes of miRNA expression in cortex of neonatal rats with hypoxic-ischemic brain injury (HIBI) and the possible roles of miRNA in the pathogenesis of HIBI, we constructed the model of rat with HIBI and the cortex tissues were obtained 14 days after the HIBI operation. The large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs of HIBI rats compared with controls. Expression of 3 miRNAs (mir-429, mir-200b, and mir-182) was determined by quantitative real-time polymerase chain reaction. The results of miRNA expression profiles indicated that 5 miRNAs were up-regulated more than twice and 29 miRNAs were down-regulated more than twice compared with the normal control group. The results of the 3 miRNAs detected by quantitative real-time polymerase chain reaction were consistent with those detected by miRNA microarray. Hypoxic ischemic brain injury rats have significant changes in miRNA expression, which demonstrated that miRNAs may play important roles in the pathogenesis of HIBI. PMID- 24220426 TI - Combination of chondroitinase ABC, glial cell line-derived neurotrophic factor and Nogo A antibody delayed-release microspheres promotes the functional recovery of spinal cord injury. AB - Spinal cord injury (SCI) is one of the most devastating injuries for patients. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor for the regeneration of the spinal neuraxial bundle, but GDNF would degrade rapidly if the protein was injected into the site of injury; thus, it cannot exert its fullest effects. Therefore, we introduced a delivery system of GDNF, poly(lactide-co-glycolic acid) (PLGA) delayed-release microspheres, in the current study and observed the effect of PLGA-GDNF and the combination of PLGA GDNF and another 2 agents PLGA-chondroitinase ABC (ChABC) and PLGA-Nogo A antibody in the treatment of SCI rats. Our results showed that PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres could elevate the locomotor scores of SCI rats. The effect of PLGA-GDNF was much better than that of GDNF. The cortical somatosensory evoked potential was also improved by PLGA GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres. Our results suggest that PLGA delayed-release microsphere may be a useful and effective tool in delivering protein agents into the injury sites of patients with SCI. This novel combination therapy may provide a new idea in promoting the functional recovery of the damaged spinal cord. PMID- 24220427 TI - Oral foregut cyst in a neonate. AB - Oral foregut cysts are congenital choristomas that arise in the oral cavity during embryonic development from remnants of foregut-derived epithelium. This is an unusual report of a neonate with a large congenital sublingual cystic lesion, extending superficially from the left ventral tongue to the anterior floor of the mouth, impeding breast-feeding. The differential diagnosis included dermoid cyst, epidermoid cyst, mucous retention cyst, and oral lymphangioma. The treatment of choice was enucleation under general anesthesia. Histology showed a cystic lesion with a ciliated pseudostratified columnar epithelium with numerous goblet cells. Immunohistochemistry was positive for cytokeratin 7 and thyroid transcription factor 1 and negative for cytokeratin 20, resulting in a final diagnosis of an oral foregut cyst. Three weeks after surgery, the tongue had healed with good mobility, and breast-feeding could be established. No recurrence was present at 6 months of follow-up. PMID- 24220428 TI - Postradiation sarcoma from a free flap. AB - INTRODUCTION: Postradiation sarcomas constitute approximately 0.5% to 5.5% of all sarcomas. They develop locally approximately 3 to 20 years after the administration of radiotherapy (RT). They are generally high-grade tumors. Osteosarcomas, fibrosarcomas, malignant fibrous histiocytoma, angiosarcomas, and leiomyosarcomas are the most frequently observed. It is rare for these tumors to originate from free flaps, and this patient report is one of the first in the literature. PATIENT: A 59-year-old man was operated on because of ethmoid sinus cancer in 2004, and the reconstruction was performed with a rectus abdominis free muscle flap. He received postoperative RT and subsequently presented to our clinic with a medially protruding mass on his upper jaw. A biopsy was performed. Its pathologic diagnosis was reported as malignant mesenchymal tumor. Computed tomography and magnetic resonance imaging were performed, demonstrating that the mass originated from the free muscle flap (m. rectus abdominis) at the front wall of the sphenoid sinus. A total excision of the free muscle flap and near-total maxillectomy were performed. The pathologic finding was reported as leiomyosarcoma with bone invasion. DISCUSSION: With the advancement of medical and pharmaceutical technologies, our patient's life expectancy is increasing. In long-living patients who have received RT, tumors can develop 20 years after the RT. The close follow-up of patients receiving RT is of utmost importance because treatment survival is linked to early diagnosis and resection with negative surgical margins. We must not forget that, even if years have passed since receiving RT, these patients may present with such tumors. PMID- 24220429 TI - Modification of mandibular advancement osteotomy in a patient with Hanhart syndrome. AB - The oromandibular limb hypogenesis syndrome is a group of anomalies affecting the mandible, tongue, and maxilla with or without reductive limb anomalies. It was first described by Hanhart in 1950. In severe syndromic cases of mandibular hypoplasia, a number of techniques have been described for mandibular advancement including sagittal split osteotomies, segmental osteotomies, or distraction osteogenesis just to name a few. A 25-year-old male patient presented to our clinic with symptoms including difficulty in speech and eating, disability in opening the mouth, together with hand and foot abnormalities; we want to describe a modification in the technique of mandibular advancement and the patient's late postoperative results. The design of the step osteotomy is modified by softening the angles of the steps and elongating the horizontal segment of the step to approximately 25 mm to allow for a more efficient advancement of the mandible. The postoperative period was uneventful, with no signs of inferior alveolar nerve disturbance. The patient showed an increase of the mouth opening distance immediately after surgery. We believe that this tongue-in-groove-like modified mandibular step osteotomy technique is a good alternative in patients where advancement greater than 15 mm is required, preserving the nerve and achieving solid bony intact surfaces. PMID- 24220430 TI - Arthroscopic surgery for removal of 112 loose bodies of synovial chondromatosis of the temporomandibular joint. AB - We present a new case of unilateral synovial chondromatosis of the temporomandibular joint, including diagnostic images, the treatment performed, and histologic analysis. In this report, we describe a case of temporomandibular joint synovial chondromatosis treated only through arthroscopy to remove 112 loose bodies completely. PMID- 24220431 TI - Giant intradiploic epidermoid cyst presenting as solitary skull mass with intracranial extension. AB - Epidermoid cysts are rare benign tumors that constitute 0.3% to 1.8% of all intracranial tumors. They are inclusion tumors that include epidermoid elements and are most commonly located in the cerebellopontine angle cistern and the parasellar region, and their location in the diploic space is very rare. These lesions slowly grow and usually do not involve the intracranial compartment. In this article, a case of giant epidermoid cyst located in the left frontal intradiploic space is presented with clinical, radiologic features and surgical treatment. PMID- 24220432 TI - Endoscopically assisted removal of a lingually displaced third molar adjacent to the inferior alveolar nerve. AB - BACKGROUND: Osteotomy of impacted lower third molars still represents a major trauma because of periosteal flap preparation and buccal bone loss. We present a new occlusal flapless approach for the removal of lingually impacted lower third molars adjacent to the inferior alveolar nerve without lateral or lingual osteotomy. METHOD: After occlusal exposure under local anesthesia, visualization of the third molar region is obtained from a posterior perspective using support endoscopy. Under magnifying endoscopic visualization, the crown is removed using an inward fragmentation technique. After exposure of the furcation area, the roots are separated and removed via the occlusal cavity. CONCLUSIONS: Endoscopically assisted removal of mandibular third molars allows the maintenance of the adjacent bone structures and the integrity of the mandibular canal. It is valuable in complex anatomic sites in particular. PMID- 24220433 TI - Bilateral parotid swelling with blindness. AB - We report a case of a 32-year-old woman who presented with bilateral parotid gland enlargement. She had no systemic symptoms such as fever, cough, and weight loss. She had bilateral blindness for a long time. The results of a physical examination revealed a bilateral firm, painless mass in the parotid region. A computed tomographic scan showed no clear lymphadenopathy in the neck but showed localized infiltrates and multiple pulmonary nodules with enlargement of the mediastinal and axillary lymph nodes in the chest. The patient underwent a superficial parotidectomy. A histopathologic finding revealed an epithelioid noncaseating granuloma, which is consistent with sarcoidosis. In summary, this current study shows that sarcoidosis should be considered in the differential diagnosis of all painless swelling of the parotid gland, especially in women, which could be an earlier complaint. PMID- 24220434 TI - Long-term complication after rhinoplasty using porous polyethylene implant: cutaneous fistula of the forehead. AB - Nasal dorsum augmentation is one of the most frequently performed procedures during rhinoplasty, especially in Asians and reconstructive cases. One can use autogenous cartilage grafts or alloplastic implants for this purpose. However, the potential for permanent damage to the skin and soft tissues as well as complications such as infection and extrusion of the implant make autogenous tissue augmentation preferable to alloplastic implantation. Furthermore, there is scant literature information about long-term outcomes and complications related to these implants. This brief report aimed to describe a unique case of migration of an alloplastic implant from the nose to the forehead, simulating a frontal sinus fistula. LEVEL OF EVIDENCE: IV. PMID- 24220435 TI - An unforeseen complication arising from inferior alveolar nerve block: is anemia possible? AB - Complications after administration of local anesthesia for dental procedures are well recognized. We present here 2 cases of patients with anemic areas on their faces resulting from inferior alveolar nerve block (IANB). The precise cause of this complication is unknown; however, it may be derived from anastomosis of the maxillary artery, rapid injection of local anesthetic solution, misdirection of the needle, and spread of the solution to the upper region of the mandible. Although neurologic occurrences resulting from IANB are rare, dentists should keep in mind that certain dental procedures such as administering IANB could cause anemic areas on the face. Henceforth, dentists should consider the possibility of anemia after administration of IANB and pay attention to avoid complications during the procedure. PMID- 24220436 TI - Multidisciplinary approach to lethal bleeding from an arteriovenous malformation in the external auditory canal. AB - Arteriovenous malformations (AVMs) are composed of abnormally connecting feeding arteries as well as draining veins and lack a regulatory system. Frequent recurrences and unpredictable behavior are their main problems. Potential mortality and morbidity associated with therapeutic procedures must be considered with these patients. Improper treatment often aggravates the condition, potentially rendering therapy more complex. A multidisciplinary approach, including an endovascular approach, surgical excision, and flap reconstruction, is considered to completely eradicate an AVM. This study introduces a complicated case of AVM with massive bleeding through the external auditory canal that was treated with a multidisciplinary approach. PMID- 24220437 TI - Keratoameloblastoma, a very rare variant of ameloblastoma. AB - The keratoameloblastoma is a rare histologic variant of ameloblastoma. Fewer than 15 cases of keratoameloblastoma have been documented in the literature. We report a new case of keratoameloblastoma in a 21-year-old female patient with a unilocular radiolucent lesion between the roots of the right mandibular incisors. We describe the clinical, radiographic, and histopathologic features of this lesion along with a review on the characteristics of previous cases. We also discuss about classification and management of this lesion. PMID- 24220438 TI - A novel approach to immediate restoration of the cosmetic deformity after regional temporalis flap reconstruction of a maxillary defect: a case report. AB - Restoration of large maxillary defects can be achieved by using various muscle and bone flap transfers. Free muscle and bone transfer has become the reconstruction standard because it offers a combination of bone and soft tissues, which allows primary closure of the defect and secondary placement of dental implants for a full rehabilitation approach. If free tissue transfer is not a viable option, regional flaps such as temporalis muscle offer a viable alternative. This report presents a novel approach to immediate reconstruction of temporalis defects after muscle transfer to repair a maxillary defect. A custom made titanium onlay was constructed preoperatively using a three-dimensional model of the patient to restore the absent muscle contour. The implant was placed at the same time as the muscle transfer. A good cosmetic outcome was achieved, and no postoperative complications were reported. PMID- 24220439 TI - Syndrome of inappropriate antidiuretic hormone secretion associated with olfactory neuroblastoma. AB - This study reports a patient having olfactory neuroblastoma complicated by syndrome of inappropriate antidiuretic hormone secretion. Olfactory neuroblastoma is a rare tumor that begins in the olfactory membrane. Only 10 cases have been reported previously. Because of having nonspecific symptoms, most patients manifest at an advanced stage at the time of diagnosis. Olfactory neuroblastoma may show local invasion and/or distant metastasis. We demonstrated preoperatively clinical and biochemical parameters consistent with antidiuretic hormone syndrome turned to normal ranges after the treatment. Surgery, chemotherapy, and radiotherapy are the choices of treatment; among these, surgery is an indispensible treatment. PMID- 24220440 TI - Ulcerated anterior maxillary swelling showing radiopaque bodies on cone beam computed tomography. AB - The calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare benign tumor of epithelial origin of locally aggressive behavior, which represents less than 1% of all odontogenic tumors affecting the oral cavity. The lesion usually presents as a nonulcerated painless mass of slow growth, commonly affecting the posterior region of the mandible. Depending on the stages of development, CEOTs may present variable radiographic appearances. To date, a few number of cases affecting the anterior maxillary region have been published in the English-language literature. This article describes an interesting and rare case of an anterior ulcerated maxillary swelling diagnosed as a CEOT based on clinical, cone beam computed tomography and pathologic findings. Functional results were obtained with the surgical approach, and no recurrence of the lesion during a 2-year follow-up period was observed. PMID- 24220441 TI - Pleomorphic adenoma of the whole parotid gland: a rare clinical finding. AB - Pleomorphic adenoma is the most common tumor arising from the parotid salivary gland. In most instances, it involves the superficial part of the gland rarely affecting the deep part, which often presents as a swelling on the lateral pharyngeal wall. The neoplastic process involving the superficial and the deep part of the same gland is extremely unusual. We had a patient who presented to our clinic with a recurrent swelling of his left parotid gland with a diagnosis of pleomorphic adenoma. On a computed tomographic scan, it was found to involve both the superficial and deep parts of the gland. The gland was excised completely, preserving the facial nerve and all its branches. A histopathologic study of the specimen confirmed the diagnosis and extent of the disease. PMID- 24220442 TI - Diffuse large B-cell lymphoma of the nasal cavity presenting as abducens nerve palsy. AB - An 87-year-old man presented with a 1-week history of transient facial numbness, followed by the onset of left diplopia 1 month later. In the neurological examination, he was found to have left abducens nerve palsy. A brain MRI showed an infiltrative lesion invading the left posterior nasal cavity and pterygopalatine fossa, and extending into the left paracavernous region. The histological diagnosis was diffuse large B-cell lymphoma. We report an unusual case of diffuse large B-cell lymphoma occurring in the sinonasal tract with unilateral abducens nerve palsy presenting as an early feature. PMID- 24220443 TI - Diagnostic challenge in papillary thyroid carcinoma with cervical lymphadenopathy, metastasis, or tuberculous lymphadenitis. AB - Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancer. Total thyroidectomy with neck dissection is recommended for treatment. Tuberculous adenitis is a common cause of lymphadenopathy in endemic areas. Therefore, tuberculous lymphadenitis should be considered in the etiology of enlarged lymph nodes when PTC patients with risk factors such as tuberculosis present with cervical lymph node enlargement. Detailed evaluation of the neck metastasis of patients with PTC is necessary to avoid postoperative complications due to neck dissection. We present a 55-year-old female patient with tuberculous lymphadenitis mimicking metastatic lymph nodes from PTC. PMID- 24220447 TI - Review of peripheral giant cell granulomas. PMID- 24220448 TI - Solitary osteoma in the zygomatic arch. PMID- 24220449 TI - Sutureless technique in third molar surgery: an overview. AB - Sutureless technique following mandibular third molar surgery is an endearing concept in modern oral and maxillofacial surgery: regardless, few articles appear in literature with different methods, results, and flaps. A modern state of the art of this technique does not exist.In this article, an overview of studies regarding sutureless technique in mandibular third molar surgery is presented: relation to postoperative infection, recovery, and proper flap are discussed. PMID- 24220450 TI - Adult sporadic parotid hemangioma with COX2 expression. PMID- 24220451 TI - Pigmented dentigerous cyst. PMID- 24220452 TI - Clinical observation of single-tooth implant in the deficient anterior maxilla with intraoral bone grafts of thin periodontal biotype patients. PMID- 24220453 TI - Propranolol as diagnostic tool for infantile hemangiomas. PMID- 24220454 TI - Bisphosphonate-associated osteonecrosis of the external auditory canal. PMID- 24220455 TI - Bilateral accessory alar lobule: report of a hidden anomaly. PMID- 24220456 TI - Dentofacial deformity is not an appropriate term. PMID- 24220457 TI - The neuronal feedback (NF) technique in third molar surgery. PMID- 24220458 TI - A useful device for the improvement of maximal interincisor opening after operations of temporomandibular region: the clothes PEG. PMID- 24220459 TI - Lung adenocarcinoma metastasis to frontal sinus mimicking Pott's puffy tumor. AB - Metastasis of the lung adenocarcinoma to the paranasal sinuses is a rare clinical entity. We present a 75-year-old male patient who presented with swelling of the forehead and left upper eyelid with proptosis in left eye due to metastasis from lung adenocarcinoma. It appears as a puffy swelling of the forehead like a Pott's puffy tumor. Pott's puffy tumor is a subperiostal abscess of the frontal bone associated with osteomyelitis and usually occurs as a complication of sinusitis or trauma. PMID- 24220460 TI - Congenital aplasia of the external ear canal and total dehiscence of mastoid tympanic segment of the facial nerve as a cause of recurrent facial paralysis. AB - Facial nerve (FN) macrodehiscence, in contrast to microdehiscence, generally occurs as a result of chronic otitis media and is rarely seen congenitally. A patient with normal hearing who had no history of ear disease or ear operation came to the clinic with recurrent facial paralysis (FP) and frequent blockage of the external ear canal with epithelial debris complaints. In the explorative ear surgery, we observed that the posterior wall of the external ear canal or tympanic ring was absent, a large external ear cavity was covered with a thin skin, the FN was under the skin, and the tympanic-mastoid segment of the FN and chorda tympani extending to the stylomastoid foramen was completely open. FP episodes were associated with the unprotected FN.To prevent an attack of FP, and to self-clean the external ears, mastoid obliteration surgery was performed, and the mastoid segment of the FN was covered with a conchal cartilage graft. This case was diagnosed as congenital aplasia of the external ear canal due to the tympanic bone aplasia-mastoid bone hypoplasia, and the dehiscence of the mastoid tympanic segment of the FN, and as a cause of recurrent FP, has never to date been identified. PMID- 24220461 TI - Intracerebral schwannoma mimicking parasagittal meningioma. AB - A 24-year-old female patient presented to the neurological department after a seizure that lasted for 10 minutes. Magnetic resonance imaging revealed a cystic and heterogeneously enhanced giant mass in the right frontal lobe mimicking parasagittal meningioma. Surgery via a single frontal craniotomy confirmed the tumor was attached to the falx cerebri and sagittal sinus. The histological diagnosis was schwannoma. Since total resection of the tumor, the patient was seizure free. Twelve months of follow-up revealed good outcome. PMID- 24220462 TI - Carcinoma ex pleomorphic adenoma in the oral cavity: a huge oral cavity mass with neck metastasis. AB - Carcinoma ex pleomorphic adenoma (CEPA) is a rare, aggressive, poorly understood malignancy. In CEPA, an epithelial malignancy develops in association with a primary or recurrent benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma is very difficult to identify before surgery because the clinical presentation of many cases is similar to that of pleomorphic adenomas. The risk for malignancy increases with the duration of a mixed tumor. Treatment of CEPA must be individualized on the basis of the tumor location, involvement of adjacent structures, histologic subtype, and grade. The authors recently experienced a case of CEPA arising in the oral cavity with neck metastasis. The patient was a 70-year-old man presenting a huge mass that was present for 20 years and that slowly grew on the left side of the neck. We treated it with a total excision with wide margins and neck dissection. There was no recurrence during the follow up period of 5 years up until now. We present a case of an unusually huge CEPA in the oral cavity. PMID- 24220463 TI - Microstrain around dental implants supporting fixed partial prostheses under axial and non-axial loading conditions, in vitro strain gauge analysis. AB - The current study used strain gauge analysis to perform an in vitro evaluation of the effect of axial and non-axial loading on implant-supported fixed partial prostheses, varying the implant placement configurations and the loading points. Three internal hexagon implants were embedded in the center of each polyurethane block with in-line and offset placements. Microunit abutments were connected to the implants using a torque of 20 N . cm, and plastic prosthetic cylinders were screwed onto the abutments, which received standard patterns cast in Co-Cr alloy (n = 10). Four strain gauges (SGs) were bonded onto the surfaces of the blocks, tangentially to the implants: SG 01 mesially to implant 1, SG 02 and SG 03 mesially and distally to implant 2, respectively, and SG 04 distally to implant 3. Each metallic structure was screwed onto the abutments using a 10-N.cm torque, and axial and non-axial loads of 30 kg were applied at 5 predetermined points. The data obtained from the strain gauge analyses were analyzed statistically through the repeated measures analysis of variance and the Tukey test, with a conventional level of significance of P < 0.05. The results showed a statistically significant difference for the loading point (P = 0.0001), with point E (nonaxial) generating the highest microstrain (327.67 MU[Latin Small Letter Open E]) and point A (axial) generating the smallest microstrain (208.93 MU[Latin Small Letter Open E]). No statistically significant difference was found for implant placement configuration (P = 0.856). It was concluded that the offset implant placement did not reduce the magnitude of microstrain around the implants under axial and non-axial loading conditions, although loading location did influence this magnitude. PMID- 24220464 TI - The use of computer-guided flapless dental implant surgery (NobelGuide) and immediate function to support a fixed full-arch prosthesis in fresh-frozen homologous patients with bone grafts. AB - The behavior of fresh-frozen homologous bone (FFB) when used in combination with computer-guided implant surgery has not been investigated yet, and there is a lack of clinical evidence in the literature. The purpose of this retrospective study is to evaluate the implant survival and related fixed full-arch prostheses at the 1- to 5-year follow-up when performed with immediate function using a flapless surgical procedure and computer-aided technology (NobelGuide; Nobel Biocare AB, Goteborg, Sweden) in patients previously treated with FFB grafts. Furthermore, the related values of torque and complications observed were analyzed and discussed. Clinical charts of patients with edentulous arches treated with FFB grafts and NobelGuide system with at least 1 year follow-up were reviewed retrospectively.A total of 65 patients met the criteria of inclusion, receiving a total of 342 implants and 77 full-arch prostheses, with a mean follow up of 32.87 months (range, 1-5 years). Survival of implants and prostheses was high, reaching 96.5% and 95%, respectively. Factors significantly related to failure of the implants were smoking, position of the implant as last distal abutment, and fracture of basal maxillary bone. Prostheses survival was influenced by bruxism, failure of multiple implants, and torque level of implant equal to 0 at implant insertion. All implants and prostheses failures occurred in the first year. A higher torque level at implant insertion did not correspond to a lower risk of implant failure.Within the limitations of our retrospective study, this treatment modality was predictable with high survival rates and high insertion torque. However, a few implant and prosthetic failures were found, together with several complications. PMID- 24220465 TI - Quality of life in patients younger than 40 years treated for anterior tongue squamous cell carcinoma. AB - This study investigated the quality of life in patients younger than 40 years with tongue squamous cell carcinoma. We used the University of Washington Head and Neck Quality of Life scale to compare the quality of life outcomes between young and old patients. Cases were patients younger than 40 years who were treated for anterior tongue squamous cell carcinoma. Controls were patients older than 40 years who were matched to the cases regarding diagnosis, sex, and TNM classification. Two controls were matched for each case; thus, 21 cases and 42 controls were selected. Twenty-one of 33 questionnaires (63.6%) were returned. The median follow-up duration was 3.7 years (range, 1-12 y). In the group of young patients, the best-scoring domains were pain, chewing, and swallowing, whereas the lowest scores were for appearance, mood, and anxiety. Young patients (40 years or younger) reported better function, notably regarding activity, recreation, shoulder, taste, and saliva compared with the old patients with anterior tongue squamous cell carcinoma. The patients younger than 40 years tend to have a good quality of life. Most of them were not significantly affected by pain. Quality of life should be used as part of our treatment of anterior tongue squamous cell carcinoma. PMID- 24220466 TI - Tonsillar leiomyosarcoma. AB - Leiomyosarcomas of the head and neck is an extremely rare entity that because of its infrequency has been associated with both delayed diagnosis and misdiagnosis. Sinonasal tract is the most common site in this region. The overall prognosis is poor. It is necessary for appropriate immunohistochemical investigation for accurate diagnosis. Tonsillar leiomyosarcoma presented only 1 case in the English language literature (PubMed, Ovid, and Proquest databases). We report a second case of leiomyosarcoma arising in the tonsil in a 38-year-old woman. LEVEL OF EVIDENCE: Level IV therapeutic study. PMID- 24220467 TI - Outcome of bone availability after secondary alveolar bone graft in two age groups. AB - The aim of this study is to evaluate outcome of bone availability after the secondary alveolar bone graft in 2 age groups: group 1 patients were between 9 and 13 years old and group 2 patients were above 14 years old. Acceptance success criteria (ASC) consisted of sufficient bone height (more than 10 mm), bone width (more than 4 mm), and adequate continuity between maxillary segments. The height and width of alveolar grafted bone were measured by using the cone-beam CT scans. We studied 45 patients who underwent a bone graft in their alveolar cleft in 2 groups (25 patients in group 1 and 20 in group 2). The results showed that as the patients' ages increased, the incidence of ASC significantly decreased. In group 1, 23 patients had ACS (92%), and in group 2, only 4 patients (20%) had ASC. Cleft type did not affect the ASC. The critical age for decreasing ASC was 14.5 years. Our study showed successful outcomes of grafted bone were good when done in the mixed dentition period. Additionally, bone availability was more predictable at the mixed dentition stage. PMID- 24220468 TI - Complete resection and immediate reconstruction with costochondral graft for recurrent aneurysmal bone cyst of the mandibular condyle. AB - Aneurysmal bone cyst is a non-neoplastic expansile lesion characterized by replacement with fibro-osseous tissue and blood-filled cavernous spaces. Involvement of the condyle is rare, and only 11 cases have been reported in English-language literature to date. Its common treatment modalities are lesion excision or condylar resection, but recurrence is high in patients treated with the former. The authors reported a 19-year-old female patient with swelling of the right preauricular region, who had a surgical curettage history in another hospital. The lesion was completely resected and the jaw was immediately reconstructed with costochondral graft with the help of SurgiCase software. The patient has been symptom-free for 6 months postoperatively. PMID- 24220469 TI - Image-guided endoscopic navigation for the precise resection of a mandibular condylar osteochondroma. AB - PURPOSE: The authors describe an intraoral approach to accessing the mandibular condyle using endoscopy combined with a navigation system and explore the feasibility of this technique for the precise excision of a benign tumor in the condyle. METHODS: The junction between the osteochondroma and the condyle was recognized and defined as the osteotomy line in a CT-based surgery planning software, and the surgical plan was then exported to a navigation system. A 4-mm diameter 30-degree endoscope was placed in the wound with direct access to the entire condyle. Based on constant feedback from the navigation system in multiplanar and 3D views, the landmarks of the osteotomy line were identified, and precise tumor resection was achieved. RESULTS: The magnified endoscopic view allowed the condylar head and neck to be easily dissected with good illumination and clear visualization. The landmarks of the osteotomy line were transferred from the virtual surgical plan to the surgical field, and precise resection of the condylar tumor was achieved. CONCLUSION: The combined technique reported in this paper could represent a valid minimally invasive approach to the ramus condyle unit for direct visualization of the medial aspect of the condyle and precise resection of benign tumor located here. PMID- 24220470 TI - Synchronous ossifying fibromas of maxilla and mandible. AB - Ossifying fibroma is a benign neoplasm composed of fibrocellular tissue and mineralized material of varying appearance, which is most commonly seen in the posterior region of the mandible as a solitary lesion. We report an unusual case of synchronous ossifying fibroma of maxilla and mandible. To the best of our knowledge, only 13 similar cases have been previously reported. PMID- 24220471 TI - Arch coordination does not affect the stability in class III orthognathic surgery patients. AB - The purpose of this study was to evaluate if the arch coordination manifested by preorthodontics had an effect on the short-term stability after orthognathic surgery by evaluating the B point, menton, overjet, and overbite. The subjects were 10 healthy adult female and male Koreans (mean age, 24.9 years) with insufficient arch coordination and 10 healthy adult female and male Koreans (mean age, 22 years) with sufficient arch coordination. All subjects had sagittal split ramus osteotomy with 1-piece maxillary Le Fort I surgery with/without genioplasty done from the same practitioner at Kyung Hee University Hospital at Gangdong from 2009 to 2011. All arch widths of the maxilla and mandible were measured. Cephalometric tracings of the subjects were made of the presurgical and postsurgical period with a follow-up at 3 months. Relapse was measured according to cephalometric tracing changes using the V-ceph Cephalometric Analysis Software version 5.5(Osstem, Seoul, South Korea). Insufficient arch coordination did not definitively affect the overall treatment outcome. There was significant difference in the horizontal dimensions of the mandible (vertical plane to point B, overjet) in the study group. The study group showed instability in orthodontic factors, whereas skeletal factors were stable. Vertical dimensions (horizontal plane to point B, horizontal plane to menton, overbite) were not statistically significant. PMID- 24220472 TI - Minimal invasive and cost-effective method in reduction of maxillofacial fracture by using a Foley catheter ballooning technique. AB - The purpose of this study was to introduce 2 successful cases of orbital inferior wall fracture and maxillary sinus anterior wall fracture using the Foley catheter ballooning technique. One patient is a 43-year-old man with left orbital inferior wall fracture. A window on the sinus was made for visualization, and a Foley catheter was accessed through the natural ostium. The ballooned catheter was inflated to lift the inferior orbital wall rim and stationed for 2 weeks. The window was closed using metal plates and screws. Another patient is a 64-year-old woman with right maxillary sinus anterior wall fracture, nasal fracture, and orbital blow-out fracture. A Foley catheter was accessed through the fractured maxillary sinus and reduced into place and fixed with absorbable plates screws. The technique of stabilization of reduced maxillofacial fractures using a Foley balloon catheter with restorable plates and titanium plates showed stable results. This technique is relatively easy to undergo with minimal or no complications because of reduced operation time. Also, it is cost-effective compared with other materials providing similar results and heightens patient satisfaction. PMID- 24220473 TI - Combined bilateral hatchet and nasolabial advancement flaps for a large defect of the lower lip. AB - A large full-thickness defect of the lower lip is difficult to reconstruct. Preservation of eating and speaking functions based on maintenance of oral sphincter and muscle function, sensation, and the oral aperture are the basic aims. It is also important to achieve a good aesthetic appearance. Here, we describe a new procedure using combined bilateral hatchet and nasolabial advancement flaps for a large full-thickness defect of the lower lip. The aim of use of the hatchet flap is to make a natural curve from the mentolabial fold to the mental protuberance using the "dog ear" resulting from suturing medially advanced bilateral hatchet flaps and to preserve a more certain blood supply to the medial edge of the flap. Our results indicate that the procedure using combined bilateral hatchet flaps and nasolabial flaps is useful for a U-shaped large full-thickness defect, with good functional and aesthetic outcomes. PMID- 24220474 TI - Traumatic lysis of the inferior rectus muscle. AB - BACKGROUND: The study aims to report a rare case of traumatic lysis of inferior rectus muscle after a traffic accident. METHODS: This is a case report wherein the clinical features, computed tomographic findings, and surgical treatment were presented. RESULTS: A 42-year-old woman complained of double vision and upward deviation of the left eye for 13 months after being involved in a traffic accident. The alternate prism and cover test both at distance and near testing showed an exotropia of 18 prism diopters (PD) and hypertropia of 50 PD of the left eye. The left eye had complete restriction of downward movement, and the forced duction test was negative. Computed tomography disclosed that the middle portion of the left inferior rectus muscle was absent. Diagnosis was traumatic lysis of left inferior rectus muscle. The deviation of the left eye was corrected by left superior rectus muscle recession and partial transposition of the medial and lateral rectus muscles. Six months after surgery, no deviation at the primary position both at distance and near testing was present; however, the left eye remained at a -3 restriction of downward movement. CONCLUSIONS: Paralysis of the inferior rectus muscle may have resulted from the traumatic lysis, a rare clinical feature that can be confirmed by computed tomography. PMID- 24220475 TI - Unusual presentation of monostatic fibrous dysplasia in zygoma. AB - Fibrous dysplasia is a nonneoplastic, developmental disease of the bone that begins in childhood with obscure etiology. Clinically, it is presented as a continuously growing, painless mass at late childhood. Maxilla and mandible are mostly involved in facial skeleton. Involvement of the zygomatic bone is rare. Fibrous dysplasia of the zygomatic bone may cause orbital dystopia, diplopia, proptosis, loss of visual acuity, swelling, mass formation, or facial asymmetry. We present 1 case of fibrous dysplasia with isolated zygomatic bone involvement. PMID- 24220476 TI - Extensive cervical necrotizing fasciitis of odontogenic origin. AB - Necrotizing fasciitis (NF) is an uncommon infection, but potentially lethal, especially when associated with systemic disorders such as diabetes. The authors report a case of necrotizing fasciitis from odontogenic origin in a patient with uncontrolled diabetes mellitus. The initial diagnosis was based on clinical information, in which multiple necrosis areas in cervical and thoracic regions were observed. Wide antibiotic therapy was applied, followed by surgical drain age and debridement. Culture was positive for methicillin-resistant Staphylococcus aureus. Although the treatment is established, the patient dies after sepsis and failure of vital organs. Clearly, the morbidity associated to this infection, even in diabetic patients, can be minimized if an early diagnosis and effective debridement are done. PMID- 24220477 TI - Wide excision and anterolateral thigh perforator flap reconstruction for dermatofibrosarcoma protuberans of the face. AB - Dermatofibrosarcoma protuberans is a rare cutaneous malignant tumor associated with a high cure rate but with a high incidence of local recurrence. Because of its tentacle-like subcutaneous infiltrating pattern that extends far beyond the clinically visible skin lesion, a wide resection margin is recommended. Hence, its localization to the head-and-neck regions, although rare, represents a real challenge for both the oncologic surgeon and the reconstructive surgeon, who aim to achieve a radical resection of the tumor with the best possible aesthetic outcome.A case of a 21-year-old Mediterranean man who presented with a 7-month history of a slowly growing subcutaneous lesion of the left preauricular region is reported. A diagnosis of dermatofibrosarcoma protuberans CD34+ was confirmed through surgical biopsy, and the patient subsequently underwent a wide en bloc local surgical resection, followed by anterolateral thigh perforator free flap reconstruction. Healing was uneventful. Initially, there was some facial nerve neurapraxia; however, this completely subsided within 3 months after the surgery. At the 13-month follow-up, the patient was completely well and free from the disease. PMID- 24220478 TI - Occupational safety threats among dental personnel and related risk factors. AB - Occupational diseases are primarily considered to be important health problems for individuals with occupations in heavy industry fields. Although dentists work in very clean and elegant offices, they are frequently exposed to various chemicals and high-intensity, sound-producing instruments, such as compressors and aerators. In our study, we aimed to investigate the risk for occupational hearing loss of dental personnel, by performing pure-tone audiometry in 40 dentists and comparing the results with those of healthy individuals. We also sampled the nasal mucosa to investigate the effects of occupational chemicals on the nasal mucosa of the dentists. The pure-tone audiometric thresholds at 5 different frequencies (1000, 2000, 4000, 6000, and 8000 Hz) and working time were evaluated as potential risk factors. The pure-tone audiometric results (as decibels) at each frequency and the median values for each side (right and left ears) were significantly higher for dentists than for the control group (P < 0.05). The pure-tone audiometric results did not significantly differ between the women and men in the study group (P > 0.05). The findings in the nasal mucosa (goblet cell hyperplasia, neutrophil/eosinophil/basophil distribution, metaplasia, dysplasia, premalignant or malignant cells) were similar in the study and control groups (P > 0.05). In conclusion, our study indicated that high intensity, sound-producing equipment is an important occupational threat for dentists, whereas chemical agents have minimal hazardous effects. PMID- 24220479 TI - Primary diffuse large B-cell lymphoma of the ethmoido-orbital region. AB - Primary paranasal sinus lymphoma is a rare presentation of extranodal non-Hodgkin lymphoma. It is less aggressive and carries a relatively better prognosis. We describe a patient with diffuse large B-cell lymphoma of the left ethmoido orbital region. PMID- 24220480 TI - A novel technique for preventing skin pressure sores using a rubber tube during surgical treatment of mandibular condyle fractures. AB - Craniofacial surgery occasionally results in sores and necrosis of the facial skin because of pressure from surgical instruments. During surgical treatment of mandibular condylar process fractures, the main mandibular fragment is routinely retracted downward using a wire to achieve a satisfactory anatomic reduction. This procedure may injure the facial skin. This potential complication is easily overlooked by medical staff, but it is easily preventable. We herein describe a method of using a rubber tube to avoid causing pressure sores of the facial skin during surgical treatment of mandibular condylar process fractures. PMID- 24220481 TI - Evaluation of preoperative model surgery and the use of a maxillary sinus surgical template in sinus floor augmentation surgery. AB - Maxillary sinus augmentation is an accepted technique for dental implant placement in presence of insufficient maxillary bone. There are various techniques in the literature, either by crestal or lateral approach in maxillary sinus augmentation that have high percentage of success, while all have complications. Schneiderian membrane perforation is the most common complication encountered during surgery. The aim of this study was to evaluate the benefits of preoperative model surgery and the ease of use of a maxillary sinus surgical template (MSST) during maxillary sinus augmentation surgery with a lateral approach. Ten patients included in the study needed rehabilitation of a partially or totally edentulous maxilla with an implant-supported fixed prosthesis and requiring sinus augmentation. A questionnaire was asked to performing surgeons, and study results showed the use of an MSST was found to be effective in terms of adaptation (62.5%), window preparation (87.5%), ease of elevation (95.9%), ease of grafting (95.9%), reduction of perforation risk (91.7%), and achieving immobility during the procedure (62.5%); however, the use of an MSST was also found to prolong the surgical procedure (100%) and restrict the view of the surgical area (79.2%). Maxillary sinus augmentation appears to be a useful tool for locating an appropriate entrance to the sinus cavity, allowing for safe elevation of the sinus membrane and effectively grafting the sinus floor. PMID- 24220482 TI - Clinical and pathological features of the giant, invasive basal cell carcinoma of the scalp. AB - BACKGROUND: The giant, invasive basal cell carcinoma of the scalp is a rare clinical form of this tumor that appears on the skin, but may spread to some of the following structures: soft tissues of the scalp, bones, meninges, and the brain. In literature, so far, it is known as the GBCC. It is caused by aggressive BCC subtypes. METHODS: We will present here a research of clinical and pathological features of 47 pathological specimens in 31 patients where the following features were examined: the dimension of the tumor, the dimension of the tissue segment, tumor area, segmentation area, resection margin width, microscopic resection margin status, tumor invasion level, and the outcome. RESULTS AND CONCLUSIONS: We have concluded that microscopic resection margin dimensions from 1 to 10 mm are safe and that relapse occurrences in giant, invasive BCCs of the scalp depend on microscopic resection margin dimensions, resection margin status, tumor invasion levels, risky occupation, and risky behavior of the patient. PMID- 24220483 TI - Nodular fasciitis in the buccal region with rapid growth after incisional biopsy mimicking sarcoma. AB - Nodular fasciitis (NF) is a reactive and proliferative fibroblastic lesion that occurs predominantly in the upper limbs but rarely develops in the oral cavity. This lesion can be misdiagnosed as malignant owing to its frequent display of rapid growth, rich cellularity, and high mitotic activity. Unlike a sarcoma, NF can resolve spontaneously or after an incisional biopsy. We describe a challenging case involving a lesion in the buccal region that rapidly enlarged after incisional biopsy. This variation of clinical behavior illustrates the difficulty in predicting whether NF will continue to grow or regress. Clinicians dealing with cases of an enlarging fibrous lesion of short duration should remain aware of this disease entity and its potential diagnostic dilemma. PMID- 24220484 TI - A basosquamous cell carcinoma of the periorbital region arising from a chronic wound created by laser ablation of a basal cell carcinoma. AB - Basosquamous cell carcinomas (BSCs) are very rare and behave aggressively, with features of both basal cell carcinoma and squamous cell carcinoma. The diagnosis of BSC includes a spectrum of histologic definitions, ranging from coexistence of basal cell carcinoma and squamous cell carcinoma with or without a transition zone, to any basal cell carcinoma with evidence of keratinization.A 63-year-old man presented with a BSC within a chronic periorbital wound, which was confirmed through a postoperative histologic examination. The wound was created from a previous laser ablation of a diagnosed basal cell carcinoma. The BSC was excised without causing any deformity, and coverage of the defect was obtained using a local perforator-based flap. No recurrence was observed during a 5-month follow up. PMID- 24220485 TI - A rare benign parotid gland tumor: angiomyolipoma. AB - Angiomyolipomas are benign neoplasms composed of smooth muscle, vasculature, and mature adipose tissue, which most commonly occur in the kidney and located in the head and neck region. A very rare neoplasm, there are only 3 cases of angiomyolipoma in the parotid gland that have been reported to date. Here, we report a case of a 38-year-old man who had a slow-growing mass in the parotid gland for the past 7 years. The results of a physical examination revealed a rubbery mass that was 2.5 cm in diameter in the below superficial lobe of the left parotid gland. A computed tomographic scan showed a heterogeneous and lobulated nodule with a well-defined margin, which was resected through partial parotidectomy with preservation of the facial nerve. A histologic finding revealed an angiomyolipoma of the parotid gland. In conclusion, angiomyolipoma should be considered in the differential diagnosis of rubbery parotid gland masses. PMID- 24220486 TI - Cavernous hemangioma with large phlebolith of the parotid gland. AB - Hemangiomas are vascular anomalies characterized by increased proliferation and turnover of endothelial cells. Hemangiomas of the parotid region are relatively uncommon in adult population, and there are a few reports of hemangioma with large phlebolith within the parotid gland. We herein report a case of it. Sialography may be a useful investigation method in the evaluation of radiopaque lesions localized intraglandularly in the parotid area to rule out the sialolith. Cavernous hemangioma with phleboliths should be included in the differential diagnosis of a swelling in the mandibular area. PMID- 24220487 TI - A randomized double-blinded placebo controlled study of four interventions for the prevention of postoperative nausea and vomiting in maxillofacial trauma surgery. AB - PURPOSE: This study aimed to determine if preoperative oral administration of metoclopramide, chlorpromazine, gabapentin, or dexamethasone would effectively reduce postoperative nausea and vomiting (PONV) in the first 24 hours after surgery in patients undergoing maxillofacial trauma surgery. METHODS: One hundred fifty patients with maxillofacial skeletal trauma that need open reduction and internal fixation were randomly assigned to receive one of the following drugs orally, 1 hour preoperative: 10 mg metoclopramide (group A), 300 mg gabapentin (group B), 100 mg chlorpromazine (group C), 5 mg dexamethasone (group D), and placebo (group E). All patients were observed in the first 24 hours for PONV. Data analysis was done with the SPSS software (version 19), using chi-square test, Fisher exact test, and multiple logistic regression methods. RESULTS: The incidence of vomiting was significantly lower in groups A (2/30), B (3/30), and C (2/30) compared with the placebo group (9/30) (P < 0.05). Also, the incidence of postoperative nausea was significantly high in the placebo group (11/30) as compared to treatment groups A (2/30), B (3/30), and C (3/30) (P < 0.05). No significant differences in the incidence of PONV were found between groups D (7/30) and E (P > 0.05). Of all demographic variables, anesthesia time (P = 0.034) and surgery time (P = 0.047) were predictors of PONV. CONCLUSION: Our results demonstrated that premedication with oral metoclopramide, gabapentin, or chlorpromazine can significantly decrease the incidence of PONV in patients undergoing maxillofacial trauma surgery. PMID- 24220488 TI - Surgical management of synchronous central giant cell granuloma and ossifying fibroma of the mandible. AB - We describe the surgical management of an uncommon case of synchronous presentation of central giant cell granuloma and ossifying fibroma in the mandible. A mandibular resection was performed and a fibula-free flap was harvested to reconstruct the defect. PMID- 24220489 TI - Reconstruction of congenital vomeral bone defect using the outer table of the skull. AB - A congenital nasal septal defect involving vomeral bone is a rare nasal anomaly, and few reconstructed cases have been reported. Reconstruction of the nasal septum using the outer table of skull to allow the use of glasses was performed. The patient's postoperative course was uneventful, and the patient was discharged on the tenth postoperative day. A transferred bone remains and shows no deviation to the right or left in the ninth postoperative month. The tubercle of the nasal part remains, and the patient is satisfied with the cosmetic result 9 months postoperatively. The timing of the operation and the surgical procedure are discussed. PMID- 24220490 TI - Brachiocephalic artery anomaly at the neck: importance during minimally invasive video-assisted parathyroidectomy. AB - A 76-year-old woman was referred to our hospital for evaluation of a parathyroid adenoma, detected on sonography. It had been located posteroinferiorly to the right thyroid lobe. Parathyroid scintigraphy confirmed the right inferior parathyroid adenoma. During physical examination of the neck, a pulsatile mass in the anterior inferior right was determined, and because of suspicion for a vascular anomaly, a computed tomography angiography was performed. The computed tomography showed that the right brachiocephalic artery ascended vertically to the level of the inferior border of right thyroid lobe and dividing into the right common carotid artery and subclavian artery at this level. Right subclavian artery after its origin brought about a curve by means of turning first posteromedially and then anterolaterally. Parathyroid adenoma remained between the right thyroid lobe, right common carotid artery, and right brachiocephalic artery. Minimally invasive video-assisted parathyroidectomy was performed and no complication appeared. PMID- 24220491 TI - Nuclease activity and protein-binding properties of a novel tetranuclear thiosemicarbazide Pt(II) complex. AB - A novel tetranuclear [Pt4(Am4M)4].16.25H2O (1), where H2Am4M is the thiosemicarbazone ligand (Z)-2-(amino(pyridin-2-yl)methylene)-N methylhydrazinecarbothioamide, has been synthesized and characterized by using various physico-chemical techniques. X-ray analysis revealed that the Pt(II) complex consists of a neutral tetranuclear [Pt4(Am4M)4] unit and abundant water molecules. The tetranuclear unit is stabilized by strong intramolecular pi-pi stacking and thus presents a ship-like eight-membered ring [Pt4S4] with four tridentate ligands peripherally coordinated to four Pt(II) ions, constituting a novel type of "well" structure. DNA and protein binding properties of complex 1 have been studied by UV and fluorescence spectroscopic methods. The binding constant (Kb = 3.05 * 10(6) M(-1)) and the apparent binding constant (Kapp = 7.732 * 10(6) M(-1)) to calf thymus DNA (CT-DNA) were accurately fitted by two respective non-linear equations, suggesting an efficient DNA intercalative binding mode which was confirmed by viscometric experiments. Furthermore, following agarose gel electrophoresis experiments, we observed that the plasmid DNA pUC19 could be completely digested by complex 1, depending on incubation time and concentration, indicating that complex 1 may possess an effective nuclease activity on DNA. Singlet oxygen ((1)O2) inhibitors showed an inhibitory effect on the cleavage. Fluorescence spectrometry also detected a medium affinity of complex 1 to bovine serum albumin (BSA) at different temperatures, which was tentatively assigned to a static binding mode. All these results suggested that this poly-Pt(II) complex might exhibit biological action as a potential chemotherapy agent. PMID- 24220492 TI - Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. AB - Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration--an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes. PMID- 24220493 TI - Lean mass as a predictor of bone density and microarchitecture in adult obese individuals with metabolic syndrome. AB - The effects of obesity and metabolic syndrome (MS) on bone health are controversial. Furthermore, the relationship between body composition and bone quality has not yet been determined in this context. The aim of this study was to investigate the correlations between body composition and bone mineral density (BMD) and bone microstructure in obese individuals with MS. This cross-sectional study assessed 50 obese individuals with MS with respect to their body composition and BMD, both assessed using dual X-ray absorptiometry, and bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia and radius. Several HR-pQCT measurements exhibited statistically significant correlations with lean mass. Lean mass was positively correlated with parameters of better bone quality (r: 0.316-0.470) and negatively correlated with parameters of greater bone fragility (r: -0.460 to 0.310). Positive correlations were also observed between lean mass and BMD of the total femur and radius 33%. Fat mass was not significantly correlated with BMD or any HR-pQCT measurements. Our data suggest that lean mass might be a predictor of bone health in obese individuals with MS. PMID- 24220494 TI - Epigallocatechin-3-gallate prevents tumor cell implantation/growth in an experimental rat bladder tumor model. AB - The aim of this study was to determine the efficacy of epigallocatechin-3-gallate (EGCG) (Polyphenon E(r)) in comparison with mitomycin C (MMC) to prevent tumor cell implantation/growth in an animal model of superficial bladder cancer and search for possible mechanism(s) of action. Female Fisher 344 rats were used to study the effects of EGCG and mitomycin C for the prevention of transitional cell tumor implantation (AY-27). Twenty rats served as a control, tumor implantation and saline wash only. Sixty rats were treated with EGCG (100, 200 and 400 uM) intravesically for 60 or 120 min after tumor implantation. Thirty other rats were divided equally and pretreated with 400 uM EGCG or saline for 120 min before tumor initiation. In a separate series of experiments, 30 rats were treated 2 weeks after tumor initiation with saline or EGCG (400 uM). In a different experiment 39 rats were treated with: saline (n=10) EGCG (n=9) 400 uM, MMC (n=10) 0.5 uM, MMC (n=10) 400 uM. Rats were sacrificed 3 weeks following treatment. Gross and histological analyses were performed on the bladders. EGCG and mitomycin C prevented intravesical tumor growth in a concentration- and time dependent manner. EGCG pretreatment or treatment 2 weeks post tumor implantation did not have therapeutic effects. Molecular modeling suggests that EGCG inhibits urokinase and matrix metalloproteinase-9. EGCG prevents intravesical tumor implantation/growth with a slightly better efficacy than mitomycin C in this experimental model. The data suggest that EGCG lowers proteolytic activity and lowers probability of cancer cell implantation rather than direct cancer cell killing. PMID- 24220495 TI - Ultrafast biexciton spectroscopy in semiconductor quantum dots: evidence for early emergence of multiple-exciton generation. AB - Understanding multiple-exciton generation (MEG) in quantum dots (QDs) requires in depth measurements of transient exciton dynamics. Because MEG typically faces competing ultrafast energy-loss intra-band relaxation, it is of central importance to investigate the emerging time-scale of the MEG kinetics. Here, we present ultrafast spectroscopic measurements of the MEG in PbS QDs via probing the ground-state biexciton transients. Specifically, we directly compare the biexciton spectra with the single-exciton ones before and after the intra-band relaxation. Early emergence of MEG is evidenced by observing transient Stark shift and quasi-instantaneous linewidth broadening, both of which take place before the intra-band relaxation. Photon-density-dependent study shows that the broadened biexciton linewidth strongly depends on the MEG-induced extra-exciton generation. Long after the intra-band relaxation, the biexciton broadening is small and the single-exciton state filling is dominant. PMID- 24220496 TI - Cardiolipin-dependent formation of mitochondrial respiratory supercomplexes. AB - The organization of individual respiratory Complexes I, III, and IV (mammalian cells) or III and IV (yeast) of the mitochondria into higher order supercomplexes (SCs) is generally accepted. However, the factors that regulate SC formation and the functional significance of SCs are not well understood. The mitochondrial signature phospholipid cardiolipin (CL) plays a central role in formation and stability of respiratory SCs from yeast to man. Studies in yeast mutants in which the CL level can be regulated displayed a direct correlation between CL levels and SC formation. Disease states in which CL levels are reduced also show defects in SC formation. Three-dimensional density maps of yeast and bovine SCs by electron cryo-microscopy show gaps between the transmembrane-localized interfaces of individual complexes consistent with the large excess of CL in SCs over that integrated into the structure of individual respiratory complexes. Finally, the yeast SC composed of Complex III and two Complexes IV was reconstituted in liposomes from purified individual complexes containing integrated CLs. Reconstitution was wholly dependent on inclusion of additional CL in the liposomes. Therefore, non-integral CL molecules play an important role in SC formation and may be involved in regulation of SC stability under metabolic conditions where CL levels fluctuate. PMID- 24220497 TI - Novel methods for liposome preparation. AB - Liposomes are bilayer vesicles which have found use, among other applications, as drug delivery vehicles. Conventional techniques for liposome preparation and size reduction remain popular as these are simple to implement and do not require sophisticated equipment. However, issues related to scale-up for industrial production and scale-down for point-of-care applications have motivated improvements to conventional processes and have also led to the development of novel routes to liposome formation. In this article, these modified and new methods for liposome preparation have been reviewed and classified with the objective of updating the reader to recent developments in liposome production technology. PMID- 24220498 TI - Membranes and mammalian glycolipid transferring proteins. AB - Glycolipids are synthesized in and on various organelles throughout the cell. Their trafficking inside the cell is complex and involves both vesicular and protein-mediated machineries. Most important for the bulk lipid transport is the vesicular system, however, lipids moved by transfer proteins are also becoming more characterized. Here we review the latest advances in the glycolipid transfer protein (GLTP) and the phosphoinositol 4-phosphate adaptor protein-2 (FAPP2) field, from a membrane point of view. PMID- 24220499 TI - Global approaches for the elucidation of phosphoinositide-binding proteins. AB - Phosphoinositide lipids (PIPns) control numerous critical biological pathways, typically through the regulation of protein function driven by non-covalent protein-lipid binding interactions. Despite the importance of these systems, the unraveling of the full scope of protein-PIPn interactions has represented a significant challenge due to the massive complexity associated with these events, including the large number of diverse proteins that bind to these lipids, variations in the mechanisms by which proteins bind to lipids, and the presence of multiple distinct PIPn isomers. As a result of this complexity, global methods in which numerous proteins that bind PIPns can be identified and characterized simultaneously from complex samples, which have been enabled by key technological advancements, have become popular as an efficient means for tackling this challenge. This review article provides an overview of advancements in large scale methods for profiling protein-PIPn binding, including experimental methods, such as affinity enrichment, microarray analysis and activity-based protein profiling, as well as computational methods, and combined computational/experimental efforts. PMID- 24220503 TI - Reprint: 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. PMID- 24220502 TI - Human BRS-3 receptor: functions/role in cell signaling pathways and glucose metabolism in obese or diabetic myocytes. AB - Several studies showed that the orphan Bombesin Receptor Subtype-3 (BRS-3) - member of the bombesin receptor family - has an important role in glucose homeostasis (v.g.: BRS-3-KO mice developed mild obesity, and decreased levels of BRS-3 mRNA/protein have been described in muscle from obese (OB) and type 2 diabetic (T2D) patients). In this work, to gain insight into BRS-3 receptor cell signaling pathways, and its implication on glucose metabolism, primary cultured myocytes from normal subjects, OB or T2D patients were tested using high affinity ligand - [d-Tyr(6),beta-Ala(11),Phe(13),Nle(14)]bombesin6-14. In muscle cells from all metabolic conditions, the compound significantly increased not only MAPKs, p90RSK1, PKB and p70s6K phosphorylation levels, but also PI3K activity; moreover, it produced a dose-response stimulation of glycogen synthase a activity and glycogen synthesis. Myocytes from OB and T2D patients were more sensitive to the ligand than normal, and T2D cells even more than obese myocytes. These results widen the knowledge of human BRS-3 cell signaling pathways induced by a BRS-3 agonist, described its insulin-mimetic effects on glucose metabolism, showed the role of BRS-3 receptor in glucose homeostasis, and also propose the employing of BRS-3/ligand system, as participant in the obese and diabetic therapies. PMID- 24220501 TI - Role of autophagy, SQSTM1, SH3GLB1, and TRIM63 in the turnover of nicotinic acetylcholine receptors. AB - Removal of ubiquitinated targets by autophagosomes can be mediated by receptor molecules, like SQSTM1, in a mechanism referred to as selective autophagy. While cytoplasmic protein aggregates, mitochondria, and bacteria are the best-known targets of selective autophagy, their role in the turnover of membrane receptors is scarce. We here showed that fasting-induced wasting of skeletal muscle involves remodeling of the neuromuscular junction (NMJ) by increasing the turnover of muscle-type CHRN (cholinergic receptor, nicotinic/nicotinic acetylcholine receptor) in a TRIM63-dependent manner. Notably, this process implied enhanced production of endo/lysosomal carriers of CHRN, which also contained the membrane remodeler SH3GLB1, the E3 ubiquitin ligase, TRIM63, and the selective autophagy receptor SQSTM1. Furthermore, these vesicles were surrounded by the autophagic marker MAP1LC3A in an ATG7-dependent fashion, and some of them were also positive for the lysosomal marker, LAMP1. While the amount of vesicles containing endocytosed CHRN strongly augmented in the absence of ATG7 as well as upon denervation as a model for long-term atrophy, denervation-induced increase in autophagic CHRN vesicles was completely blunted in the absence of TRIM63. On a similar note, in trim63(-/-) mice denervation-induced upregulation of SQSTM1 and LC3-II was abolished and endogenous SQSTM1 did not colocalize with CHRN vesicles as it did in the wild type. SQSTM1 and LC3-II coprecipitated with surface-labeled/endocytosed CHRN and SQSTM1 overexpression significantly induced CHRN vesicle formation. Taken together, our data suggested that selective autophagy regulates the basal and atrophy-induced turnover of the pentameric transmembrane protein, CHRN, and that TRIM63, together with SH3GLB1 and SQSTM1 regulate this process. PMID- 24220500 TI - The yeast sphingolipid signaling landscape. AB - Sphingolipids are recognized as signaling mediators in a growing number of pathways, and represent potential targets to address many diseases. The study of sphingolipid signaling in yeast has created a number of breakthroughs in the field, and has the potential to lead future advances. The aim of this article is to provide an inclusive view of two major frontiers in yeast sphingolipid signaling. In the first section, several key studies in the field of sphingolipidomics are consolidated to create a yeast sphingolipidome that ranks nearly all known sphingolipid species by their level in a resting yeast cell. The second section presents an overview of most known phenotypes identified for sphingolipid gene mutants, presented with the intention of illuminating not yet discovered connections outside and inside of the field. PMID- 24220504 TI - Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. METHODS/DESIGN: This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. DISCUSSION: This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-13003418. PMID- 24220505 TI - Disruption of Aspm causes microcephaly with abnormal neuronal differentiation. AB - AIMS: A number of ASPM mutations have been detected in primary microcephaly patients. In order to evaluate the function of ASPM in brain development, we generated model animals of human autosomal recessive primary microcephaly-5 (MCPH5). METHODS: In the Aspm knock-out mice, the exon 2-3 of the Aspm gene was encompassed by a pair of loxP signals so that cre-recombinase activity switched the allele from wild-type to null zygotes as frequently, as expected from the Mendelian inheritance. We precisely analyzed the brains of adults and fetuses using immunohistochemistry and morphometry. RESULTS: The adult brains of the Aspm(-/-) mice were smaller, especially in the cerebrum. In the barrel field of the somatosensory cortex, layer I was significantly thicker, whereas layer VI was significantly thinner in Aspm(-/-) mice, compared with Aspm(+/+) mice. The total number of cells and the thickness of the cortical plate at embryonic day 16.5 was significantly decreased in Aspm(-/-) mice, compared with Aspm(+/+) mice. Furthermore, the expression of transcription factors, such as Tbr1 and Satb2, was significantly increased in the subplate of the Aspm(-/-) mice. CONCLUSIONS: The results suggested that Aspm is essential to the proliferation and differentiation of neural stem/progenitor cells. The Aspm gene loss model provided a novel pathogenetic insight into acquired microcephaly, which can be caused by in utero exposure to both known and unknown teratogens. PMID- 24220506 TI - Spatial self-organization favors heterotypic cooperation over cheating. AB - Heterotypic cooperation-two populations exchanging distinct benefits that are costly to produce-is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In 'partner choice', cooperators recognize and choose cooperating over cheating partners; in 'partner fidelity feedback', fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001. PMID- 24220507 TI - Essential yet limited role for CCR2+ inflammatory monocytes during Mycobacterium tuberculosis-specific T cell priming. AB - Defense against infection by Mycobacterium tuberculosis (Mtb) is mediated by CD4 T cells. CCR2(+) inflammatory monocytes (IMs) have been implicated in Mtb specific CD4 T cell responses but their in vivo contribution remains unresolved. Herein, we show that transient ablation of IMs during infection prevents Mtb delivery to pulmonary lymph nodes, reducing CD4 T cell responses. Transfer of MHC class II-expressing IMs to MHC class II-deficient, monocyte-depleted recipients, while restoring Mtb transport to mLNs, does not enable Mtb-specific CD4 T cell priming. On the other hand, transfer of MHC class II-deficient IMs corrects CD4 T cell priming in monocyte-depleted, MHC class II-expressing mice. Specific depletion of classical DCs does not reduce Mtb delivery to pulmonary lymph nodes but markedly reduces CD4 T cell priming. Thus, although IMs acquire characteristics of DCs while delivering Mtb to lymph nodes, cDCs but not moDCs induce proliferation of Mtb-specific CD4 T cells. DOI: http://dx.doi.org/10.7554/eLife.01086.001. PMID- 24220508 TI - Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics. AB - The presynaptic active zone proteins UNC-13/Munc13s are essential for synaptic vesicle (SV) exocytosis by directly interacting with SV fusion apparatus. An open question is how their association with active zones, hence their position to Ca(2+) entry sites, regulates SV release. The N-termini of major UNC-13/Munc13 isoforms contain a non-calcium binding C2A domain that mediates protein homo- or hetero-meric interactions. Here, we show that the C2A domain of Caenorhabditis elegans UNC-13 regulates release probability of evoked release and its precise active zone localization. Kinetics analysis of SV release supports that the proximity of UNC-13 to Ca(2+) entry sites, mediated by the C2A-domain containing N-terminus, is critical for accelerating neurotransmitter release. Additionally, the C2A domain is specifically required for spontaneous release. These data reveal multiple roles of UNC-13 C2A domain, and suggest that spontaneous release and the fast phase of evoked release may involve a common pool of SVs at the active zone. DOI: http://dx.doi.org/10.7554/eLife.01180.001. PMID- 24220509 TI - CO2directly modulates connexin 26 by formation of carbamate bridges between subunits. AB - Homeostatic regulation of the partial pressure of CO2 (PCO2) is vital for life. Sensing of pH has been proposed as a sufficient proxy for determination of PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A 'carbamylation motif', present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from a CO2-insensitive connexin (Cx31), comprises Lys125 and four further amino acids that orient Lys125 towards Arg104 of the adjacent subunit of the connexin hexamer. Introducing the carbamylation motif into Cx31 created a mutant hemichannel (mCx31) that was opened by increases in PCO2. Mutation of the carbamylation motif in Cx26 and mCx31 destroyed CO2 sensitivity. Course-grained computational modelling of Cx26 demonstrated that the proposed carbamate bridge between Lys125 and Arg104 biases the hemichannel to the open state. Carbamylation of Cx26 introduces a new transduction principle for physiological sensing of CO2. DOI: http://dx.doi.org/10.7554/eLife.01213.001. PMID- 24220510 TI - Deprivation-related and use-dependent plasticity go hand in hand. AB - Arm-amputation involves two powerful drivers for brain plasticity-sensory deprivation and altered use. However, research has largely focused on sensory deprivation and maladaptive change. Here we show that adaptive patterns of limb usage after amputation drive cortical plasticity. We report that individuals with congenital or acquired limb-absence vary in whether they preferentially use their intact hand or residual arm in daily activities. Using fMRI, we show that the deprived sensorimotor cortex is employed by whichever limb individuals are over using. Individuals from either group that rely more on their intact hands (and report less frequent residual arm usage) showed increased intact hand representation in the deprived cortex, and increased white matter fractional anisotropy underlying the deprived cortex, irrespective of the age at which deprivation occurred. Our results demonstrate how experience-driven plasticity in the human brain can transcend boundaries that have been thought to limit reorganisation after sensory deprivation in adults. DOI: http://dx.doi.org/10.7554/eLife.01273.001. PMID- 24220511 TI - Dissecting apoptosis the omics way. AB - A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells. PMID- 24220513 TI - Analysis of c.801-2A>G mutation in the DNAJC6 gene in Parkinson's disease in southern Spain. PMID- 24220512 TI - Gold nanoparticle based Tuberculosis immunochromatographic assay: the quantitative ESE Quanti analysis of the intensity of test and control lines. AB - A rapid dual channel lateral flow assay for the detection of Mycobacterium Tuberculosis antibodies (MTB 38 kDa monoclonal antibody) in human blood was developed. The MTB 6-14-38 kDa fusion antigen and anti-Protein A were used as the capture proteins for test and control lines respectively. Protein A labeled 40 nm gold nanoparticles were used as the detection conjugate. Whole blood and serum were spiked with MTB 38 kDa monoclonal antibody to make a positive sample model. The developed lateral flow was used to test MTB 38 kDa monoclonal antibody, and a detection limit of 5 ng/ml was used as a cut-off concentration of the analytes. The effect of the analyte concentration on the MTB lateral flow assay was studied using the variation of the intensity obtained from a ESE Quanti reader. There was a direct correlation between the analyte (MTB 38 kDa monoclonal antibody) concentration and the intensity of the test line. The intensity increased with an increase in the concentration of MTB 38 kDa monoclonal antibody, while in contrast, an increase in analyte concentration decreased the intensity of the control line. PMID- 24220514 TI - Mobilization patterns of patients after an acute myocardial infarction: a pilot study. AB - This study was aimed to identify the mobilization patterns of acute myocardial infarction (AMI) patients during their first three days in the coronary care unit (CCU) by performing a prospective observational pilot study design. The study included 31 diagnosed AMI patients admitted to three CCUs. Mobilization patterns classified as bed rest, semi-fowler, transfer to chair, and standing/walking were documented by CCU nurses for 72 consecutive hours after patient admission to the CCU. Of 2,232 possible mobilization periods (72 hr * 31 patients), 1,385 recorded observations of mobilization (62%) were obtained. Bed rest and semi-fowler positions were the most common mobilization patterns; together they accounted for 70% of the documented positions over the first 72 hr in the CCU. Patients who experience an uncomplicated AMI spend the majority of their first 72 hr in CCU in bed. PMID- 24220516 TI - Review: the transcriptional and signalling networks of mouse trophoblast stem cells. AB - Trophoblast stem cells (TSCs) are a self-renewing stem cell population derived from the early trophoblast lineage, analogous to embryonic stem cells (ESCs) that can be generated from the inner cell mass (ICM) of the mouse blastocyst. In that sense TSCs and ESCs reflect the earliest lineage differentiation event after fertilization. TSCs are characterized by an indefinite proliferation potential and by multipotency, i.e. the ability to differentiate into all the various trophoblast cell types of the placenta. These properties are driven by specific signalling pathways orchestrating characteristic transcriptional outputs. Here we review the recent advances in studying the signalling cascades and the transcriptional regulatory networks that define specification and maintenance of TSCs, and provide a future outlook of TSC research. PMID- 24220515 TI - Risk-taking behavior among adolescents with prenatal drug exposure and extrauterine environmental adversity. AB - OBJECTIVE: High-risk environments characterized by familial substance use, poverty, inadequate parental monitoring, and violence exposure are associated with an increased propensity for adolescents to engage in risk-taking behaviors (e.g., substance use, sexual behavior, and delinquency). However, additional factors such as drug exposure in utero and deficits in inhibitory control among drug-exposed youth may further influence the likelihood that adolescents in high risk environments will engage in risk-taking behavior. This study examined the influence of prenatal substance exposure, inhibitory control, and sociodemographic/environmental risk factors on risk-taking behaviors in a large cohort of adolescents with and without prenatal cocaine exposure (PCE). METHOD: Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age. RESULTS: Prenatal cocaine exposure predicted later arrests and early onset of sexual behavior in controlled analyses. Associations were partially mediated, however, by adolescent inhibitory control problems. PCE was not associated with substance use at this age. In addition, male gender, low parental involvement, and violence exposure were associated with greater odds of engaging in risk taking behavior across the observed domains. CONCLUSIONS: Study findings substantiate concern regarding the association between prenatal substance exposure and related risk factors and the long-term outcomes of exposed youth. Access to the appropriate social, educational, and medical services is essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes and incarceration), especially among high-risk adolescent youth and their families. PMID- 24220517 TI - Strongly emissive long-lived 3IL excited state of coumarins in cyclometalated Ir(III) complexes used as triplet photosensitizers and application in triplet triplet annihilation upconversion. AB - Three different coumarin chromophores were used to prepare the Ir(III) complexes, i.e. coumarin 6 (Ir-1), 7-diethylamino coumarin (Ir-2) and x-phenyl-y diethylamino coumarin (Ir-3). Ir(ppy)2(bpy)[PF6] was used as the reference complex (Ir-0). The coumarin units were connected to the coordination center of the complexes by using a C=C pi-conjugation bond. The photophysical properties of the complexes were studied with steady state and time-resolved absorption and luminescence spectroscopy, low-temperature luminescence (77 K), as well as DFT calculations. All the three new complexes show strong absorption of visible light (molar absorption coefficient epsilon is up to 42,000 M(-1) cm(-1) at 487 nm) and a long-lived triplet excited state (tauT = 65.9 MUs), compared to the reference complex Ir(ppy)2(bpy)[PF6], which shows the typical weak visible light-absorption (epsilon < 5000 M(-1) cm(-1) in the region beyond 400 nm) and a short triplet excited state (tauT = 0.3 MUs). Interestingly the long-lived triplet excited states are strongly phosphorescent (quantum yield is up to 18.2%, with emission maxima at 607 nm), which is rare for phosphorescent transition metal complexes. With nanosecond time-resolved transient difference absorption spectroscopy we proved that a coumarin-localized triplet excited state ((3)IL) was produced upon photoexcitation. The complexes were used as triplet photosensitizers for triplet triplet annihilation upconversion and upconversion quantum yields up to 22.8% were observed. Our results are useful for the preparation of visible light harvesting transition metal complexes, the study of the triplet excited state of organic chromophores, as well as the application of these visible light harvesting transition metal complexes as efficient triplet photosensitizers. PMID- 24220519 TI - The future of electronic health records. PMID- 24220518 TI - Prevalence of psbA-containing cyanobacterial podoviruses in the ocean. AB - Podoviruses that infect marine picocyanobacteria are abundant and could play a significant role on regulating host populations due to their specific phage-host relationship. Genome sequencing of cyanophages has unveiled that many marine cyanophages encode certain photosynthetic genes like psbA. It appears that psbA is only present in certain groups of cyanopodovirus isolates. In order to better understand the prevalence of psbA in cyanobacterial podoviruses, we searched the marine metagenomic database (GOS, BATS, HOT and MarineVirome). Our study suggests that 89% of recruited cyanopodovirus scaffolds from the GOS database contained the psbA gene, supporting the ecological relevance of the photosynthesis gene for surface oceanic cyanophages. Diversification between Clade A and B are consistent with recent finding of two major groups of cyanopodoviruses. All the data also shows that Clade B cyanopodoviruses dominate the surface ocean water, while Clade A cyanopodoviruses become more important in the coastal and estuarine environments. PMID- 24220520 TI - What has replaced foundation programme work-based assessments? PMID- 24220522 TI - Classical Hodgkin's lymphoma: past, present and future perspectives. PMID- 24220523 TI - Computed tomography urography 2: clinical applications. PMID- 24220524 TI - Colorectal disorders during pregnancy: a review. PMID- 24220525 TI - Nasal obstruction in children. PMID- 24220526 TI - Pre-excitation on the electrocardiogram: what next? PMID- 24220527 TI - Edwin Klebs: discoverer of the bacillus of diphtheria. PMID- 24220528 TI - A cry for help: time to re-think the patient call bell in an ageing population. AB - Historically, the patient call bell has been the mechanism by which patients can alert a health-care worker to provide help. The authors were concerned that, in an increasingly comorbid population, this method of raising help was not fit for purpose. They therefore reviewed every level 3 bed space (n = 283) in a district general hospital over a 2-week period and assessed the usability of the call bell at each occupied bed. The call bells were on average 82 cm away from the bed. More worryingly, over one third (38.1%) of all inpatients were unable to understand independently the role of the call bell and how to use it. The authors conclude that, in times of immense inpatient bed pressures, it is critical that there are robust strategies to highlight the significant number of patients who cannot use the call bell and ensure they are given an appropriate ward location. PMID- 24220529 TI - The Best Practice Tariff helps improve management of neck of femur fractures: a completed audit loop. AB - BACKGROUND: The Best Practice Tariff incentivizes hospitals in the UK to improve the care they deliver, and includes a requirement to deliver multiprofessional care to patients with neck of femur fractures. The Best Practice Tariff for 2010 11 included six targets: (1) surgery within 36 hours, (2) admission under consultant-led joint orthopaedic-geriatric care, (3) admission using a multidisciplinary assessment protocol, (4) review by a geriatrician within 72 hours, (5) geriatrician-directed multi-professional rehabilitation, and (6) assessment for falls and bone protection. The authors chose to audit their Trust's compliance with these targets. METHODS: A retrospective audit was conducted in 2011 at the authors' university-affiliated tertiary care hospital, which is a regional major trauma centre. Only patients 65 years or older, with fragility-type neck of femur fractures who were treated surgically at the authors' unit and were eligible for geriatric review and multiprofessional rehabilitation, were included. The results of this audit (2010-11 Best Practice Tariff targets) were analysed and a series of procedural and logistical measures were introduced. A re-audit was performed in April 2012 for 2011-12, and the results for the 2 years were compared using appropriate statistics (Chi square tests and analysis of variance). Thirty-day mortality was compared using the summary hospital-level mortality indicator. RESULTS: A total of 410 patients were eligible for Best Practice Tariff in 2010-11, which increased to 463 in 2011-12. The changes from the first year's audit helped increase the rates for 36-hour surgery from 48.3% to 73.4% and for 72-hour geriatric review from 68.8% to 81.8% (P<0.05). The annual Best Practice Tariff achievement increased from 31.7% to 61.3% (P<0.05). The summary hospital-level mortality indicator declined from 96.5 to 61.3. CONCLUSIONS: Focusing on poorly satisfied Best Practice Tariff indicators can produce a significant improvement in the per capita Best Practice Tariff achievement. Further studies are needed to assess the health and financial gain in detail. PMID- 24220530 TI - Adenoma with rectal villous diarrhoea and severe hypokalaemia (McKittrick Wheelock syndrome). PMID- 24220531 TI - Fever, rash and neutrophilia: not always an infectious cause. PMID- 24220532 TI - Painful nodule at the laparoscopic port site. PMID- 24220534 TI - Protecting you and your family's income. PMID- 24220533 TI - Spontaneous rupture of the spleen resulting from infectious mononucleosis. PMID- 24220535 TI - Use of CT-PET imaging investigation of pyrexia of unknown origin. PMID- 24220537 TI - Gelatin solutions for critically unwell septic adults. PMID- 24220538 TI - Mindfulness and acceptance-based group therapy versus traditional cognitive behavioral group therapy for social anxiety disorder: a randomized controlled trial. AB - Recent research has supported the use of mindfulness and acceptance-based interventions for Social Anxiety Disorder (SAD). OBJECTIVE: The purpose of the present study was to compare mindfulness and acceptance-based group therapy (MAGT) with cognitive behavioral group therapy (CBGT) with respect to outcome. It was hypothesized that MAGT and CBGT would both be superior to a control group but not significantly different from one another. METHOD: Individuals (N = 137, mean age = 34 years, 54% female, 62% White, 20% Asian) diagnosed with SAD were randomly assigned to MAGT (n = 53), CBGT (n = 53) or a waitlist control group (n = 31). The primary outcome was social anxiety symptom severity assessed at baseline, treatment midpoint, treatment completion, and 3-month follow-up. Secondary outcomes were cognitive reappraisal, mindfulness, acceptance, and rumination. Depression, valued living, and group cohesion were also assessed. RESULTS: As hypothesized, MAGT and CBGT were both more effective than the control group but not significantly different from one another on social anxiety reduction and most other variables assessed. CONCLUSIONS: The present research provides additional support for the use of mindfulness and acceptance-based treatments for SAD, and future research should examine the processes by which these treatments lead to change. PMID- 24220539 TI - Predictive codes of familiarity and context during the perceptual learning of facial identities. AB - Face recognition is a key component of successful social behaviour. However, the computational processes that underpin perceptual learning and recognition as faces transition from unfamiliar to familiar are poorly understood. In predictive coding, learning occurs through prediction errors that update stimulus familiarity, but recognition is a function of both stimulus and contextual familiarity. Here we show that behavioural responses on a two-option face recognition task can be predicted by the level of contextual and facial familiarity in a computational model derived from predictive-coding principles. Using fMRI, we show that activity in the superior temporal sulcus varies with the contextual familiarity in the model, whereas activity in the fusiform face area covaries with the prediction error parameter that updated facial familiarity. Our results characterize the key computations underpinning the perceptual learning of faces, highlighting that the functional properties of face-processing areas conform to the principles of predictive coding. PMID- 24220541 TI - Involvement of autophagy in tri-ortho-cresyl phosphate- induced delayed neuropathy in hens. AB - Autophagy is a highly conserved cellular self-degradative process that plays a housekeeping role in removing aggregated proteins and damaged organelles. Our recent work has found that tri-ortho-cresyl phosphate (TOCP), a neuropathic organophosphate (OP), decreased the level of beclin 1 (a key molecule in the process of autophagy) in hen nerve tissues (Song et al., 2012). However, the role of autophagy in the pathogenesis of organophosphorus ester-induced delayed neuropathy (OPIDN) remains unclear. Here, we investigated whether dysfunctional autophagy was associated with the initiation and development of TOCP-induced delayed neuropathy. Adult hens were given a single dose of 750mg/kg TOCP (p.o.) and sacrificed on days 1, 5, 10, and 21 after dosing, respectively. The formation of autophagosomes in spinal cord motor neurons was observed by transmission electron microscopy, the level of autophagy-related proteins in hen spinal cords and tibial nerves was determined by Western blot analysis. The results demonstrated that the number of autophagosomes was markedly increased in the myelinated and unmyelinated axons of hen spinal cords after TOCP exposure. In the meantime, the level of two molecular markers for autophagy, microtubule associated protein light chain-3 (LC3) and p62/SQSTM1 in hen nerve tissues was significantly decreased and increased, respectively. Furthermore, a marked reduction in autophagy-regulated proteins including ULK 1, AMBRA 1, ATG 5, ATG 7, ATG 12 and VPS34 expression was also observed. Our results suggested that the administration of TOCP resulted in a significant inhibition of autophagy activity in neurons, which might be associated with the pathogenesis of OPIDN. PMID- 24220540 TI - Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6 hydroxydopamine-induced cytotoxicity. AB - Oxidative stress-induced neuronal death plays a pivotal role in pathogenesis of neurodegenerative disorders. Recently, 7,8-dihydroxyflavone (7,8-DHF) has been shown to exert neuroprotective effects by acting as a selective tyrosine kinase receptor B (TrkB) agonist. In addition, the antioxidant action of 7,8-DHF may protect neuronal cells against oxidative injury. In the present study, we used PC12 cells, a cell line generally thought to lack TrkB, to investigate the effect of 7,8-DHF on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and the underlying mechanism. We found that 7,8-DHF effectively prevented cell death, apoptosis and mitochondrial dysfunction induced by 6-OHDA. In a cell free system, 7,8-DHF did not slow down extracellular auto-oxidation of 6-OHDA which may generate H2O2. However, We found that 7,8-DHF dramatically reduced cellular malondialdehyde content and phospho-histone H2A.X protein level. 7,8-DHF also elevated total superoxide dismutase activity in 6-OHDA-treated cells. These results indicate that 7,8-DHF might protect PC12 cells against 6-OHDA-induced cytotoxicity through its powerful antioxidant activity. By acting as a potent TrkB agonist and an antioxidant together with its easiness to pass across blood-brain barrier, 7,8 DHF may be developed into a promising candidate in treatment of neurodegenerative diseases. PMID- 24220543 TI - Enzymatic membrane reactor for full saccharification of ionic liquid-pretreated microcrystalline cellulose. AB - Ultrafiltration reactors based on polymeric or ceramic membranes were shown to be suitable catalytic systems for fast enzymatic saccharification of cellulose, allowing the full recovery and reuse of enzymes. By pre-treating cellulose with the IL 1-butyl-3-methylimidazolium chloride, the suitability of this substrate for enzymatic saccharification in a reactor based on polymeric ultrafiltration membranes was demonstrated, leading to 95% cellulose hydrolysis in 4h at 50 degrees C. The filtration process gave a clear glucose solution (up to 113 mM) at constant permeate flow (24.7 L h(-1) m(-2)), allowing the enzyme to be reused for 9 operation cycles under semi-continuous operation, without any loss of enzyme activity. Under continuous operation mode and using ceramic ultrafiltration membranes at different residence times, the enzymatic reactor showed constant profiles in both the permeate flow rate and the glucose concentration, demonstrating the excellent suitability of the proposed approach for the saccharification of cellulose. PMID- 24220542 TI - Astrocytic p-connexin 43 regulates neuronal autophagy in the hippocampus following traumatic brain injury in rats. AB - Gap junctions are conductive channels formed by membrane proteins termed connexins, which permit the intercellular exchange of metabolites, ions and small molecules. Previous data demonstrated that traumatic brain injury (TBI) activates autophagy and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining predominantly in neurons. Although previous studies have identified several extracellular factors that modulate LC3 expression, knowledge of the regulatory network controlling LC3 in health and disease remains incomplete. The aim of the present study was to assess whether gap junctions control the in vivo expression of LC3 in TBI. Using a modified weight-drop device, adult male Sprague-Dawley rats (weight, 350-375 g) were subjected to TBI. Phosphorylated gap junction protein levels and LC3-II levels were quantified using western blot analysis. The spatial distribution of immunoreactivity for phosphorylated connexin 43 (p-CX43) and LC3-II was analyzed by immunofluorescence. The results showed that p-CX43 expression in the hippocampus reached a maximum level 6 h following injury. In addition, the immunoreactivity of p-CX43 was localized in the astrocytes surrounding pyramidal neurons. The LC3 II protein content remained at high levels 24 h following injury. Double immunolabeling demonstrated that LC3-II dots colocalized with the hippocampus pyramidal neurons. Furthermore, inhibition of p-CX43 reduced TBI-induced autophagy, according to western blot analysis. As astrocytic gap junction coupling is affected in various forms of brain injury, the results suggest that point gap junctions/connexins are important regulators of autophagy in the hippocampal neurons following TBI. PMID- 24220544 TI - The future viability of algae-derived biodiesel under economic and technical uncertainties. AB - This study presents a techno-economic assessment of algae-derived biodiesel under economic and technical uncertainties associated with the development of algal biorefineries. A global sensitivity analysis was performed using a High Dimensional Model Representation (HDMR) method. It was found that, considering reasonable ranges over which each parameter can vary, the sensitivity of the biodiesel production cost to the key input parameters decreases in the following order: algae oil content>algae annual productivity per unit area>plant production capacity>carbon price increase rate. It was also found that the Return on Investment (ROI) is highly sensitive to the algae oil content, and to a lesser extent to the algae annual productivity, crude oil price and price increase rate, plant production capacity, and carbon price increase rate. For a large scale plant (100,000 tonnes of biodiesel per year) the production cost of biodiesel is likely to be L0.8-1.6 per kg. PMID- 24220545 TI - Greenhouse gas emissions from home composting in practice. AB - In Sweden, 16% of all biologically treated food waste is home composted. Emissions of the greenhouse gases CH4 and N2O and emissions of NH3 from home composts were measured and factors affecting these emissions were examined. Gas and substrate in the compost bins were sampled and the composting conditions assessed 13 times during a 1-year period in 18 home composts managed by the home owners. The influence of process parameters and management factors was evaluated by regression analysis. The mean CH4 and N2O concentration was 28.1 and 5.46 ppm (v/v), respectively, above the ambient level and the CH4:CO2 and N2O:CO2 ratio was 0.38% and 0.15%, respectively (median values 0.04% and 0.07%, respectively). The home composts emitted less CH4 than large-scale composts, but similar amounts of N2O. Overall NH3 concentrations were low. Increasing the temperature, moisture content, mixing frequency and amount of added waste all increased CH4 emissions. PMID- 24220546 TI - Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy. AB - AIM: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). METHODS: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). RESULTS: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p<0.001), negative preoperative lymph node status (p=0.011), comparable tumor diameter at mammography and at ultrasound (p=0.001), negative HER2 status (p=0.044), and absence of invasive lobular cancer (p=0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. CONCLUSIONS: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted. PMID- 24220547 TI - Adolescent depressive disorders and family based interventions in the Family Options multicenter evaluation: study protocol for a randomized controlled trial. AB - BACKGROUND: There is increasing community and government recognition of the magnitude and impact of adolescent depression. Family based interventions have significant potential to address known risk factors for adolescent depression and could be an effective way of engaging adolescents in treatment. The evidence for family based treatments of adolescent depression is not well developed. The objective of this clinical trial is to determine whether a family based intervention can reduce rates of unipolar depressive disorders in adolescents, improve family functioning and engage adolescents who are reluctant to access mental health services. METHODS/DESIGN: The Family Options study will determine whether a manualized family based intervention designed to target both individual and family based factors in adolescent depression (BEST MOOD) will be more effective in reducing unipolar depressive disorders than an active (standard practice) control condition consisting of a parenting group using supportive techniques (PAST). The study is a multicenter effectiveness randomized controlled trial. Both interventions are delivered in group format over eight weekly sessions, of two hours per session. We will recruit 160 adolescents (12 to 18 years old) and their families, randomized equally to each treatment condition. Participants will be assessed at baseline, eight weeks and 20 weeks. Assessment of eligibility and primary outcome will be conducted using the KID-SCID structured clinical interview via adolescent and parent self-report. Assessments of family mental health, functioning and therapeutic processes will also be conducted. Data will be analyzed using Multilevel Mixed Modeling accounting for time x treatment effects and random effects for group and family characteristics. This trial is currently recruiting. Challenges in design and implementation to date are discussed. These include diagnosis and differential diagnosis of mental disorders in the context of adolescent development, non-compliance of adolescents with requirements of assessment, questionnaire completion and treatment attendance, breaking randomization, and measuring the complexity of change in the context of a family-based intervention. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry Title: engaging youth with high prevalence mental health problems using family based interventions; number 12612000398808. Prospectively registered on 10 April 2012. PMID- 24220548 TI - Angiotensin (1-7) increases the potassium current and the resting potential of arterial myocytes from vascular resistance vessels of normal adult rats: Pathophysiological implications. AB - The influence of angiotensin (Ang) (1-7) on potassium current (Kv) and resting potential of smooth muscle cells isolated from mesenteric artery of Sprague Dawley rats was investigated. Measurements of potassium current were performed using the whole cell configuration of pCLAMP. The results indicated that Ang (1 7) (10(-9) M) increased the potassium current by 120% +/- 2.6% (P < .05) and the resting potential of smooth muscle cells by 8 +/- 2.8 mV (n = 23; P < .05). Ang II (10(-9) M) administered to the bath reduced the potassium current by 35% +/- 3.6% (n = 23; P < .05) and depolarized the arterial myocytes by 7.8 +/- 2.1 mV (n = 25; P < .05). The effect of the heptapeptide on potassium current was inhibited by a Mas receptor inhibitor (A779; 10(-8) M) as well as by a protein kinase A (PKA) inhibitor (10(-9) M) dialyzed into the cell. Intracellular dialysis of the catalytic subunit of PKA (5 * 10(-8) M) enhanced the potassium current by 38% +/- 3.4% (n = 14; P < .05) but did not abolish the effect of Ang (1-7). On the other hand, Bis-1 (10(-9) M), which is a specific inhibitor of PKC, suppressed the effect of Ang (1-7) on potassium current. In conclusion, Ang (1-7) counteracts the effect of Ang II on potassium current and membrane potential of smooth muscle cells from mesenteric arteries, which are resistance vessels involved in the regulation of peripheral resistance and blood pressure. The activation of the cAMP/PKA cascade is essential for the effect of the heptapeptide. Pathophysiological implications are discussed. PMID- 24220549 TI - Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives. AB - Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID- 24220550 TI - Effect of maintaining neck flexion on anti-saccade reaction time: an investigation using transcranial magnetic stimulation to the frontal oculomotor field. AB - BACKGROUND: Reaction time for anti-saccade, in which the gaze is directed to the position opposite to an illuminated target, shortens during maintenance of neck flexion. The present study applied transcranial magnetic stimulation (TMS) to the frontal oculomotor field, and investigated the effect of maintaining neck flexion on information processing time in the anti-saccade neural pathway before the frontal oculomotor field. METHODS: The reaction time was measured with the chin resting on a stand ('chin-on' condition) and with voluntary maintenance of neck flexion ('chin-off' condition) at 80% maximal neck flexion angle, with and without TMS. The TMS timing producing the longest prolongation of the reaction time was first roughly identified for 10 ms intervals from 0 to 180 ms after the target presentation. Thereafter, TMS timing was set finely at 2 ms intervals from -20 to +20 ms of the 10 ms step that produced the longest prolongation. RESULTS: The reaction time without TMS was significantly shorter (21.9 ms) for the chin off (235.9 +/- 14.9 ms) than for the chin-on (257.5 +/- 17.1 ms) condition. Furthermore, TMS timing producing maximal prolongation of the reaction time was significantly earlier (18.6 ms) for the chin-off than the chin-on condition. The ratio of the forward shift in TMS timing relative to the reduction in reaction time was 87.8%. CONCLUSIONS: We confirmed that information processing time in the anti-saccade neural pathway before the frontal oculomotor field shortened while neck flexion was maintained, and that this reduction time accounted for approximately 88% of the shortening of reaction time. PMID- 24220551 TI - Enzymatic creatinine assays allow estimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation. AB - The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m2 should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m2, both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m2. Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m2 with MDRD and 120 mL/min/1.73 m2 with CKD-EPI equation. PMID- 24220552 TI - Evaluation of ultrasensitive cardiac Troponin I levels in patients with breast cancer during chemotherapy. PMID- 24220553 TI - Reprint: 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk. PMID- 24220554 TI - Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. AB - PURPOSE: The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations. METHODS: The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement. RESULTS: The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements. CONCLUSION: Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist. PMID- 24220555 TI - Randomized, multicenter, phase II study of CO-101 versus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma: including a prospective evaluation of the role of hENT1 in gemcitabine or CO-101 sensitivity. AB - PURPOSE: Gemcitabine requires transporter proteins to cross cell membranes. Low expression of human equilibrative nucleoside transporter-1 (hENT1) may result in gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). CO-101, a lipid-drug conjugate of gemcitabine, was rationally designed to enter cells independently of hENT1. We conducted a randomized controlled trial to determine whether CO-101 improved survival versus gemcitabine in patients with metastatic PDAC (mPDAC) with low hENT1. The study also tested the hypothesis that gemcitabine is more active in patients with mPDAC tumors with high versus low hENT1 expression. PATIENTS AND METHODS: Patients were randomly assigned to CO-101 or gemcitabine, after providing a metastasis sample for blinded hENT1 assessment. An immunohistochemistry test measuring tumor hENT1 was developed. To dichotomize the population, an hENT1 cutoff value was defined using primary PDAC samples from an adjuvant trial, and a high/low cutoff was applied. The primary end point was overall survival (OS) in the low hENT1 subgroup. RESULTS: Of 367 patients enrolled, hENT1 status was measured in 358 patients (97.5%). Two hundred thirty two (64.8%) of 358 patients were hENT1 low. There was no difference in OS between treatments in the low hENT1 subgroup or overall, with hazard ratios (HRs) of 0.994 (95% CI, 0.746 to 1.326) and 1.072 (95% CI, 0.856 to 1.344), respectively. The toxicity profiles in both arms were similar. Within the gemcitabine arm, there was no difference in survival between the high and low hENT1 subgroups (HR, 1.147; 95% CI, 0.809 to 1.626). CONCLUSION: CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome. PMID- 24220556 TI - Transcription factor STAT3 as a prognostic marker and therapeutic target in cancer. PMID- 24220557 TI - Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. AB - PURPOSE: Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. METHODS: Recurrence Score was assessed in 892 fixed, paraffin embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. RESULTS: Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. CONCLUSION: The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer. PMID- 24220558 TI - Response to A.A.M. van der Veldt et al. PMID- 24220559 TI - De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. AB - PURPOSE: The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity. PATIENTS AND METHODS: Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of <= 50%, and 35 (56.5%) had an ejection fraction of > 50% and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension [Corrected]. Primary end point was overall response rate at the end of treatment. RESULTS: Thirty-eight patients (61.3%; 95% CI, 49.2 to 73.4) achieved disease response (complete response [CR], n = 18; undocumented/unconfirmed CR, n = 6; partial response, n = 14). Two-year progression-free survival for all patients was 49.8% (95% CI, 37.3 to 62.3), and 2-year overall survival was 55.8% (95% CI, 43.3 to 68.4). Thirty-four patients experienced grade >= 3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population. CONCLUSION: Our phase II multicenter trial showed that the R-GCVP regimen is an active, reasonably well tolerated treatment for patients with DLBCL for whom anthracycline-containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease. PMID- 24220560 TI - Reply to R.J. Chan. PMID- 24220561 TI - Is antiviral prophylaxis necessary to prevent hepatitis B virus (HBV) reactivation in patients with HBV-resolved infection receiving rituximab containing chemotherapy? PMID- 24220562 TI - Reply to S. Kusumoto et al. PMID- 24220564 TI - Do nursing interventions targeting concurrent symptoms hold promise for managing fatigue in patients with advanced cancer? PMID- 24220565 TI - Pituitary gland: do anticancer drugs sit in the Turkish saddle? PMID- 24220563 TI - Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP. AB - PURPOSE: We previously reported that constitutive STAT3 activation is a prominent feature of the activated B-cell subtype of diffuse large B-cell lymphomas (ABC DLBCL). In this study, we investigated whether STAT3 activation can risk stratify patients with DLBCL. PATIENTS AND METHODS: By an immunohistochemical method, we investigated phosphotyrosine STAT3 (PY-STAT3) expression from 185 patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Cell line-based siRNA experiments were also performed to generate an 11-gene, PY-STAT3 activation signature, which was used to study a previously published cohort of 222 patients with DLBCL. The STAT3 activation status determined by these two methods and by STAT3 mRNA levels were then correlated with survival. RESULTS: PY-STAT3 was detected in 37% of DLBCL and enriched in ABC-DLBCL cases (P = .03). PY-STAT3 positivity significantly correlated with poor overall survival (OS; P = .01) and event-free survival (EFS; P = .006). Similar observations were made for high levels of STAT3 mRNA. In multivariable analysis, PY-STAT3 status (P = .02), International Prognostic Index (P = .02), and BCL2 expression (P = .046) were independent prognosticators of OS in this cohort. Among the cell-of-origin subgroups, PY-STAT3 was associated with poor EFS among non-germinal center B-cell DLBCL cases only (P = .027). Similarly, the 11-gene STAT3 activation signature correlated with poor survival in the entire DLBCL cohort (OS, P < .001; EFS, P < .001) as well as the ABC-DLBCL subgroup (OS, P = .029; EFS, P = .025). CONCLUSION: STAT3 activation correlated with poor survival in patients with DLBCL treated with R-CHOP, especially those with tumors of the ABC-DLBCL subtype. PMID- 24220566 TI - Menstrual phase as predictor of outcome after mild traumatic brain injury in women. AB - OBJECTIVE: To determine whether menstrual cycle phase in women at the time of mild traumatic brain injury (mTBI) predicts 1-month outcomes. SETTING: Six emergency departments; 5 in Upstate New York, and 1 in Pennsylvania. PARTICIPANTS: One hundred forty-four female participants (age, 16-60) who presented to participating emergency departments within 4 hours of mTBI. DESIGN: Nested cohort study with neurologic and quality-of-life outcome assessment, 1 month after enrollment. Female subjects aged 16 to 60 enrolled in the parent cohort study, with 1-month neurological determination data available, were classified into menstrual cycle groups by serum progesterone concentration and self-reported contraceptive use. MAIN MEASURES: Rivermead Post Concussion Questionnaire and EuroQoL/EQ5D. RESULTS: Women injured during the luteal phase of their menstrual cycle, when progesterone concentration is high, had significantly lower EuroQoL General Health Ratings and Index Scores than women injured during the follicular phase of their cycle or women taking oral contraceptives. Multivariate analysis confirmed a significant independent effect of menstrual cycle phase on EuroQoL Index Score and the Rivermead Post Concussion Questionnaire Somatic Subscore. CONCLUSION: Menstrual cycle phase and progesterone concentration at the time of mTBI affect 1-month quality-of-life and neurologic outcomes. This association has important implications for treatment and prognosis after mTBI. PMID- 24220567 TI - PACAP and PAC1 receptor in brain development and behavior. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) act through three class B G-protein coupled receptors, PAC1, VPAC1 and VPAC2, initiating multiple signaling pathways. In addition to natural peptides ligands, a number of synthetic peptides and a small molecular antagonist have been generated. Genetically modified animals have been produced for the neuropeptides and receptors. Neuroanatomical, electrophysiological, behavioral and pharmacological characterization of the mutants and transgenic mice uncovered diverse roles of PACAP-PAC1-VAPC2 signaling in peripheral tissues and in the central nervous system. Human genetic studies suggest that the PACAP PAC1-VPAC2 signaling can be associated with psychiatric illness via mechanisms of not only loss-of-function, but also gain-of-function. For example, a duplication of chromosome 7q36.3 (encoding the VPAC2 receptor) was shown to be associated with schizophrenia, and high levels of PACAP-PAC1 signaling are associated with posttraumatic stress disorder. Whereas knockout animals are appropriate to address loss-of-function of human genetics, transgenic mice overexpressing human transgenes in native environment using artificial chromosomes are particularly valuable and essential to address the consequences of gain-of-function. This review focuses on role of PACAP and PAC1 receptor in brain development, behavior of animals and potential implication in human neurodevelopmental disorders. It also encourages keeping an open mind that alterations of VIP/PACAP signaling may associate with psychiatric illness without overt neuroanatomic changes, and that tuning of VIP/PACAP signaling may represent a novel avenue for the treatment of the psychiatric illness. PMID- 24220568 TI - Cortical spreading depression and calcitonin gene-related peptide: a brief review of current progress. AB - Although detailed disease mechanisms of migraine remain poorly understood, migraine is known to have a complex pathophysiology with both vascular and neuronal mechanisms. The neuronal mechanisms of migraine may be attributed to cortical spreading depression (CSD); consequently, CSD has been widely studied for understanding the pathophysiology of migraine. Well validated CSD models have been developed for evaluating anti-migraine drugs. Neuropeptides, mainly, calcitonin gene-related peptide (CGRP), have been proposed as an emerging class of effective drugs against migraine headache. The central role of this neuropeptide has led to research into CSD for understanding disease mechanisms of migraine. This review briefly summarizes our current understanding of CSD and CGRP involvement in CSD. Although CSD can also worsen strokes, this brief paper has excluded the possible connection between the neuropeptide and CSD associated with them. Instead it has focused solely on CGRP in CSD associated with migraine. PMID- 24220569 TI - Biomarkers in the management of breast cancer: great expectations, hard times. AB - Progress in biomarkers research has resulted in increasing awareness of the heterogeneity of breast cancer. The identification of subtypes with different clinical behavior and the possibility of using targeted therapy in specific subgroup of patients (eg, those with tumors overexpressing HER2) raise expectations for increasing personalization of treatment. However, there is a widening gap between scientific discoveries and practical application in everyday practice: too many patients are still being managed based only on traditional clinical and pathologic parameters, because of lack of access to up to date technology-such as gene profiling, or cell proliferation assays-in many cancer centers in the United Kingdom. In this article, we provide some examples of this contrast, drawn from the literature and from our own clinical experience in South West Wales, and discuss possible solutions. PMID- 24220570 TI - Activated boron nitride as an effective adsorbent for metal ions and organic pollutants. AB - Novel activated boron nitride (BN) as an effective adsorbent for pollutants in water and air has been reported in the present work. The activated BN was synthesized by a simple structure-directed method that enabled us to control the surface area, pore volume, crystal defects and surface groups. The obtained BN exhibits an super high surface area of 2078 m(2)/g, a large pore volume of 1.66 cm(3)/g and a special multimodal microporous/mesoporous structure located at ~ 1.3, ~ 2.7, and ~ 3.9 nm, respectively. More importantly, the novel activated BN exhibits an excellent adsorption performance for various metal ions (Cr(3+), Co(2+), Ni(2+), Ce(3+), Pb(2+)) and organic pollutants (tetracycline, methyl orange and congo red) in water, as well as volatile organic compounds (benzene) in air. The excellent reusability of the activated BN has also been confirmed. All the features render the activated BN a promising material suitable for environmental remediation. PMID- 24220571 TI - Allospecific CD8 T suppressor cells induced by multiple MLC stimulation or priming in the presence of ILT3.Fc have similar gene expression profiles. AB - Alloantigen specific CD8 T suppressor cells can be generated in vitro either by multiple stimulations of CD3 T cells with allogeneic APC or by single stimulation in primary MLC containing recombinant ILT3.Fc protein. The aim of the present study was to determine whether multiple MLC stimulation induced in CD8(+) CD28(-) T suppressor cells molecular changes that are similar to those observed in CD8 T suppressor cells from primary MLC containing ILT3.Fc protein. Our study demonstrates that the characteristic signatures of CD8 T suppressor cells, generated by either of these methods are the same consisting of up-regulation of the BCL6 transcriptional repressor and down-regulation of inflammatory microRNAs, miR-21, miR-30b, miR-146a, and miR-155 expression. In conclusion microRNAs which are increased under inflammatory conditions in activated CD4 and CD8 T cells with helper or cytotoxic function show low levels of expression in CD8 T cells which have acquired antigen-specific suppressor activity. PMID- 24220572 TI - Functional characterization of a plastid-specific ribosomal protein PSRP2 in Arabidopsis thaliana under abiotic stress conditions. AB - Plastids possess a small set of proteins unique to plastid ribosome, named plastid-specific ribosomal proteins (PSRPs). Among the six PSRPs found in Arabidopsis thaliana, PSRP2 is unique in that it harbors two RNA-recognition motifs found in diverse RNA-binding proteins. A recent report demonstrated that PSRP2 is not essential for ribosome function and plant growth under standard greenhouse conditions. Here, we investigated the functional role of PSRP2 during Arabidopsis seed germination and seedling growth under different light environments and various stress conditions, including high salinity, dehydration, and low temperature. The transgenic Arabidopsis plants overexpressing PSRP2 showed delayed germination compared with that of the wild-type plants under salt, dehydration, or low temperature stress conditions. The T-DNA insertion psrp2 mutant displayed better seedling growth but PSRP2-overexpressing transgenic plants showed poorer seedling growth than that of the wild-type plants under salt stress conditions. No noticeable differences in seedling growth were observed between the genotypes when grown under different light environments including dark, red, far-red, and blue light. Interestingly, the PSRP2 protein possessed RNA chaperone activity. Taken together, these results suggest that PSRP2 harboring RNA chaperone activity plays a role as a negative regulator in seed germination under all three abiotic stress conditions tested and in seedling growth of Arabidopsis under salt stress but not under cold or dehydration stress conditions. PMID- 24220573 TI - Excellent prognosis of node negative patients after sentinel node procedure in colon carcinoma: a 5-year follow-up study. AB - AIM: Investigate the prognostic impact and clinical relevance of the sentinel node (SN)-procedure in colon carcinoma. PATIENTS AND METHODS: Between May 2002 and January 2004, the SN-procedure was performed in 55 patients that underwent elective resection for clinically non-advanced colon carcinoma. A control group of 110 patients was identified from a cohort between January 2000 and April 2002. All lymph nodes were analysed by conventional haematoxylin-eosin staining. All negative SNs underwent in-depth analysis using immunohistochemical-staining and automated microscopy with the Ariol-system. Patients with positive lymph nodes were offered adjuvant chemotherapy. All patients were routinely monitored at 6 month intervals and follow-up was more than 5 years. RESULTS: The SN was successfully identified in 98% of the patients, with 94% sensitivity. In-depth analysis with immunohistochemistry and automated microscopy (Ariol-system) upstaged 3 and 4 patients respectively. When only node-negative patients were analysed, overall 5-year-survival was significantly better in the SN group (91% vs. 76%, p = 0.04). Cancer-specific-mortality was even 0% (vs. 8%, p = 0.08). Disease-free-survival was significantly improved to 96% (vs. 77%, p < 0.01). CONCLUSIONS: This study describes the prognostic impact of the SN-procedure in colon carcinoma after 5-year-follow-up. Only one patient had recurrent disease after a negative SN procedure (disease-free-survival 96%). These results indicate that the SN-procedure is of prognostic relevance and might be useful to select patients for adjuvant chemotherapy. Patients that are lymph node negative after an SN-procedure have an excellent prognosis and do not need adjuvant treatment. PMID- 24220574 TI - Have rates of behavioral health assessment and treatment increased for Massachusetts children since the Rosie D. decision? A report from two primary care practices. AB - Following a court decision (Rosie D. v. Romney), the Medicaid program in Massachusetts launched the statewide Children's Behavioral Health Initiative in 2008 to increase the recognition and treatment of behavioral health problems in pediatrics. We reviewed billing data (n = 64,194) and electronic medical records (n = 600) for well child visits in pediatrics in 2 practices to examine rates of behavioral health screening, problem identification, and treatment among children seen during the year before and 2 years after the program's implementation. According to electronic medical records, the percentage of well child visits that included any form of behavioral health assessment increased significantly during the first 2 years of the program, and pediatricians significantly increased their use of standardized screens. According to billing data, behavioral health treatment increased significantly. These findings suggest that behavioral health screening and treatment have increased following the Rosie D. decision. PMID- 24220576 TI - Fluoroquinolones and peripheral neuropathy. PMID- 24220575 TI - Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif. AB - MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA 'superfamily' consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFbeta and p53 pathways by the miR-17-19-130 superfamily members. PMID- 24220577 TI - Electronic cigarettes. PMID- 24220578 TI - An OTC corticosteroid nasal spray for allergic rhinitis. PMID- 24220579 TI - A prostatic urethral lift for benign prostatic hyperplasia. PMID- 24220580 TI - A meningococcal vaccine for infants. PMID- 24220581 TI - Asthma and the socio-economic reality in Brazil. AB - BACKGROUND: Asthma is a prevalent disease that is considered a health problem worldwide. The aim of this study was to analyze the clinical and socioeconomic characteristics of a cohort of asthmatics receiving specialized outpatient treatment in a tertiary/teaching public hospital in Brazil. METHODS: Persistent asthmatics older than 5 years old were consecutively included. They received clinical treatment at 3- to 4-month intervals and were interviewed 2 times at 6 month intervals over a 12-month observation period. The data were collected directly from the patients or their parents by 2 researchers who did not participate in their clinical care. The primary variables were age, gender, education level, monthly family income, place of residence, number of lost days of school or work, BMI, the severity and control level of asthma, the number of scheduled and non-scheduled visits and hospitalization days and the best peak flow measurement. RESULTS: Of the 117 participants, 108 completed the study. Of the participants, 73.8% were women, and 25.0% lived outside the county. Of those who lived within the county, 60.1% lived in areas far from the health care unit. The majority (83.3%) had associated rhinitis, and more than 50.0% were overweight or obese, in whom the prevalence of severe asthma was greater (p = 0.001). The median monthly income was US$ 536.58 and was greater among the patients with controlled asthma (p = 0.005 and p = 0.01 at the start and the end of the study, respectively). In the initial evaluation, 16 participants had severe asthma, and in the final evaluation, 8 out of 21 patients with uncontrolled asthma had improved. Three-quarters of the students and half of the workers had missed days of school or work, respectively. The asthmatic population in this study had medium to low socioeconomic status in Brazil and socioeconomic status was associated with overweigth/obesity and with poor control of asthma. CONCLUSION: Asthma has a great impact on absenteeism in Brazil. Lower monthly family income and body weight above the ideal level were associated with greater severity and worse control of asthma. PMID- 24220582 TI - Prenatal detection of TAR syndrome in a fetus with compound inheritance of an RBM8A SNP and a 334-kb deletion: a case report. AB - Thrombocytopenia-absent radius syndrome (TAR) is a rare genetic disorder that is characterized by the absence of the radius bone in each forearm and a markedly reduced platelet count that results in life-threatening bleeding episodes (thrombocytopenia). Tar syndrome has been associated with a deletion of a segment of 1q21.1 cytoband. The 1q21.1 deletion syndrome phenotype includes Tar and other features such as mental retardation, autism and microcephaly. This study describes a case of a prenatally diagnosed fetus with compound inheritance of a small (334 kb) deletion, as detected by array-comparative genomic hybridization, and a 5' untranslated region (UTR) low-frequency allele (rs139428292) in gene RBM8A as detected by Sanger sequencing. The study describes the first case of prenatal analysis of TAR syndrome in a fetus with compound inheritance of a 334 kb deletion in the 1q21.1 region and a low-frequency 5' UTR single nucleotide polymorphism, and provides confirmation of the causal nature of the RBM8A gene in the diagnosis of TAR syndrome. PMID- 24220583 TI - The aryl hydrocarbon receptor nuclear translocator (ARNT) modulates the antioxidant response in AML cells. AB - We observed AML cell lines vary in their sensitivity to induction of apoptosis by troglitazone (TG), which induces apoptosis through the generation of intracellular reactive oxygen species (ROS). TG-resistant cell lines had increased abundance of ARNT transcripts and protein. Expression of ARNT in TG sensitive cells made these cells resistant to both TG and daunorubicin. ARNT expressing cells had increased expression of SOD2 and Nrf2 transcripts and elevated intracellular GSH concentration. Our results indicate that ARNT expression in AML cells augments antioxidant response and confers resistance to ROS inducers. This suggests ARNT may modulate ROS signaling and drug response in AML. PMID- 24220584 TI - Current pathology practices in and barriers to MDS diagnosis. AB - Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell malignancies that represent a diagnostic challenge for pathologists. Accurate classification and prognostic scoring are essential to treating MDS. To understand factors that affect MDS management, a case-based survey was distributed to hematopathologists (n=53) and general pathologists (n=72) to identify perceived barriers, attitudes, and practices in MDS diagnosis. Results demonstrated confidence and practice gaps. Only 33% of general pathologists are confident in diagnosing MDS. Neither general pathologists nor hematopathologists are comfortable using the International Prognostic Scoring System to characterize risk. Thirty percent of general pathologists and 22% of hematopathologists would not include bone marrow aspirate and cytogenetics in initial testing of a neutropenic patient. Most practitioners tested appropriately for disease classification and prognosis; discrepancies were identified in testing to differentiate MDS from acute myeloid leukemia and testing in post treatment specimens. These results have implications in the management of MDS. PMID- 24220585 TI - Investigation clues for prognosis, diagnosis and therapeutic strategies. PMID- 24220586 TI - Genetics of diastolic heart failure. AB - Heart failure explains a large portion of heart diseases. Molecular mechanisms determining cardiac function, by inference dysfunction in heart failure, are incompletely understood, especially in the common (or congestive) systolic (SHF) and diastolic heart failure (DHF). Limited genome-wide association studies (GWASs) in humans are reported on SHF and no GWAS has been performed on DHF. Genetic analyses in a rodent model of true DHF, Dahl salt-sensitive (DSS) rats, have begun to unravel the genetic components determining diastolic function. Diastolic dysfunction of DSS rats can be ameliorated or even normalized by distinct quantitative trait loci (QTLs), designated as diastolic function/blood pressure QTLs (DF/BP QTLs), which also affect blood pressure (BP). However, an improvement in diastolic dysfunction is merely transitory from a single DF/BP QTL, despite a permanent lowering of BP. A long-term protection against diastolic dysfunction can be realized only through combining specific DF/BP QTLs. Moreover, the worsening diastolic dysfunction with age can also be reversed in a different combination of DF/BP QTLs. Thus, distinct genes in combinations must be involved in the physiological mechanisms ameliorating or reversing diastolic dysfunction. As not all the QTLs that influence BP can affect diastolic function, it is not BP reduction itself that restores diastolic function, but rather specific genes that are uniquely integrated into the pathways of blood pressure homeostasis as well as diastolic function. Thus, the elucidation of pathophysiological mechanisms causal to hypertensive diastolic dysfunction will not only provide new diagnostic tools, but also novel therapeutic targets and strategies in reducing, curing, and even reversing DHF. PMID- 24220587 TI - Aortic stiffening, cerebral resistance vessel function and structure, and cerebral perfusion. PMID- 24220588 TI - Night-time blood pressure and new onset kidney disease. PMID- 24220589 TI - Cardiovascular risk in Mozambique: who should be treated for hypertension? AB - AIM: To estimate the proportion of Mozambicans eligible for pharmacological treatment for hypertension, according to single risk factor and total cardiovascular risk approaches. METHODS: A representative sample of Mozambicans aged 40-64 years (n=1116) was evaluated according to the WHO STEPwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). We measured blood pressure (BP) and 12-h fasting blood glucose levels and collected data on sociodemographic characteristics, smoking, and use of antidiabetic and antihypertensive drugs. We estimated the 10-year risk of a fatal or nonfatal major cardiovascular event (WHO/International Society of Hypertension risk prediction charts), and computed the proportion of untreated participants eligible for pharmacological treatment for hypertension, according to BP values alone and accounting also for the total cardiovascular risk (WHO guidelines for assessment and management of cardiovascular diseases). RESULTS: Among the Mozambicans aged 40-64 years and not taking antihypertensive drugs, less than 4% were classified as having cardiovascular risk at least 20% whereas the prevalence of SBP/DBP at least 140/90 mmHg was nearly 40%. A total of 19.8% of 40-64-year-olds would be eligible for pharmacological treatment of hypertension according to the WHO guidelines, all of whom had SBP/DBP at least 160/100 mmHg. CONCLUSION: Among the Mozambicans aged 40-64 years not taking antihypertensive drugs and having SBP/DBP at least 140/90 mmHg, only half were eligible for pharmacological treatment according to the WHO guidelines. Taking the latter into account, when defining strategies to control hypertension at a population level, may allow a more efficient use of the scarce resources available in developing settings. PMID- 24220590 TI - P2X7 receptor polymorphisms do not influence endothelial function and vascular tone in neo-diagnosed, treatment-naive essential hypertensive patients. AB - OBJECTIVE: Endothelial dysfunction and arterial stiffness are early vascular alterations, linked to oxidative stress and inflammation, with prognostic significance in essential hypertensive patients. P2X7 receptors (P2X7R), responding to extracellular ATP, are encoded by a highly polymorphic gene and modulate inflammatory responses and cell growth, potentially playing a role in the control of vascular tone. This study evaluated the effects of P2X7R gene polymorphisms (single nucleotide polymorphisms, SNPs) on a detailed vascular hypertensive phenotype. METHODS: We determined by real-time PCR two SNPs of the P2X7R gene (489C>T and 1513A>C) in 134 newly diagnosed, treatment-naive essential hypertensive patients and 131 normotensive controls (CTL). Endothelium-dependent response was assessed as flow-mediated dilatation (FMD) of the brachial artery, arterial stiffness as aortic pulse wave velocity (PWV) and augmentation index (AIx) by tonometry. Markers of oxidative stress were also measured. RESULTS: FMD was lower (P < 0.05), whereas aortic PWV and AIx were higher (P < 0.01) in essential hypertensive patients than in CTL. The allelic distribution of the two P2X7R SNPs was similar in essential hypertensive patients and CTL, either concerning homozygosis or presence of the mutant alleles. No difference was observed for FMD, aortic PWV, AIx or markers of oxidative stress between carriers and noncarriers of the mutant alleles, either in essential hypertensive patients and in CTL. In the whole group, logistic regression showed that the mutant allele of 1513A>C was a main determinant of AIx (odds ratio 1.90; P = 0.03). CONCLUSION: P2X7R 489C>T and 1513A>C SNPs are not associated with altered endothelial function or arterial stiffness in untreated newly diagnosed essential hypertensive patients; a possible role in influencing peripheral wave reflection should be further addressed. PMID- 24220591 TI - Central artery stiffness, neuropsychological function, and cerebral perfusion in sedentary and endurance-trained middle-aged adults. AB - BACKGROUND: Midlife vascular disease risk is a strong risk factor for late-life dementia. Central arterial stiffness, a hallmark of vascular aging, is associated with accelerated brain aging and cognitive decline. Habitual aerobic exercise is an effective lifestyle strategy to reduce central arterial stiffness and is related to lower risk of cognitive impairment. OBJECTIVE: To determine the associations among cardiopulmonary fitness, neuropsychological function, central arterial stiffness, and cerebral perfusion in the sedentary and endurance-trained middle-aged adults. METHODS: Twenty-six sedentary and 32 endurance-trained middle aged adults were measured for maximal oxygen consumption, central arterial stiffness determined by aortic pulse wave velocity and carotid ultrasound, neuropsychological function, and regional cerebral blood flow assessed by MRI. RESULTS: There were no group differences in age, sex, ethnicity, education, blood pressure, and carotid intima-media wall thickness (all P>0.05). Neuropsychological performance and occipitoparietal perfusion were greater, and central arterial stiffness was lower in endurance-trained individuals than in sedentary individuals (all P<0.05). Greater cardiopulmonary fitness was related to better cognitive composite scores, including memory and attention-executive function (r=0.28-0.40, P<0.05). Lower carotid arterial stiffness was associated with better neuropsychological outcome independent of age, sex, and education (r= 0.32 to -0.35, P<0.05), and correlated with greater occipitoparietal blood flow (r= -0.37 to -0.51, P<0.05). CONCLUSION: Lower carotid artery stiffness in endurance-trained adults is associated with better neuropsychological outcome and greater occipitoparietal perfusion. PMID- 24220592 TI - Impact of hypertension on infarct size in ST elevation myocardial infarction patients undergoing primary angioplasty. AB - BACKGROUND: Hypertension is a well known risk factor for atherosclerosis. However, data on the impact of hypertension in patients with ST-segment elevation myocardial infarction (STEMI) are inconsistent, and mainly related to studies performed in the thrombolytic era, with very few data on patients undergoing primary angioplasty. The aim of the current study was to evaluate the impact of hypertension on scintigraphic infarct size in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHOD: Our population is represented by 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi. RESULTS: Hypertension was associated with more advanced age (P<0.001), a larger prevalence of diabetes (P=0.001), female sex (P<0.001), but lower prevalence of smoking (P<0.001) and anterior infarction (P=0.042). No difference was observed in ischemia time, cardiogenic shock at presentation, in preprocedural thrombolysis in myocardial infarction (TIMI) flow, and collateral circulation. Hypertension did not affect the rate of postprocedural TIMI 3 flow. Hypertension did not affect infarct size [12.5% (4.1 23.8%) vs. 12.8% (4.3-24.7%), P=0.38]. Similar results were observed in subanalyses in major high-risk subgroups. No impact of hypertension on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median [adjusted odds ratio (95% CI)=0.97 (0.72-1.33), P=0.92]. CONCLUSION: This study shows that among STEMI patients, undergoing primary PCI hypertension does not affect scintigraphic infarct size. PMID- 24220593 TI - Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis. AB - BACKGROUND: The aim of our study was to assess the prevalence of pseudo resistance caused by noncompliance with treatment among patients with severe resistant hypertension and to analyze the contributing factors. METHOD: Three hundred and thirty-nine patients (195 men) with resistant essential hypertension were studied. The first group consisted of 176 patients admitted for hospitalization for exclusion of a secondary cause to our hypertension centre (103 men); the second one consisted of 163 out-patients (92 men) investigated for the first time in an out-patient hypertension clinic. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by means of liquid chromatography-mass spectrometry was performed in all patients. RESULTS: Our main finding is a surprisingly low compliance with drug treatment in out-patients with resistant hypertension (23% partially noncompliant and 24% totally noncompliant - in total, 47% prevalence of noncompliance). Eighty-one percent of hospitalized patients were positive, in 10% the results were partially positive and in 9% of the patients, the drugs were all negative. The compliance among hospitalized patients was probably better due to lower numbers of prescribed drugs and expected thorough investigation. More frequently, noncompliance was found in nonworking (potential purpose-built behaviour), younger and less well educated patients. The most frequent noncompliance was to doxazosine, spironolactone and hydrochlorothiazide. We have observed a surprisingly low compliance with treatment among out-patients with severe hypertension. CONCLUSION: We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation. PMID- 24220594 TI - New blood pressure control goals, more rational but facilitating therapeutic inertia? PMID- 24220595 TI - New blood pressure control goals, more rational but facilitating therapeutic inertia? : reply. PMID- 24220596 TI - Guidelines for the management of hypertension and target organ damage. PMID- 24220597 TI - Guidelines for the management of hypertension and target organ damage: reply. PMID- 24220598 TI - Reprint: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. PMID- 24220600 TI - Laparoscopic Heller myotomy versus endoscopic balloon dilatation for the treatment of achalasia: a network meta-analysis. AB - OBJECTIVE: Comparison of short- and long-term effects after laparoscopic Heller myotomy (LHM) and endoscopic balloon dilation (EBD) considering the need for retreatment. BACKGROUND: Previously published studies have indicated that LHM is the most effective treatment for Achalasia. In contrast to that a recent randomized trial found EBD equivalent to LHM 2 years after initial treatment. METHODS: A search in Medline, PubMed, and Cochrane Central Register of Controlled Trials was conducted for prospective studies on interventional achalasia therapy with predefined exclusion criteria. Data on success rates after the initial and repeated treatment were extracted. An adjusted network meta-analysis and meta regression analysis was used, combined with a head-to-head comparison, for follow up at 12, 24, and 60 months. RESULTS: Sixteen studies including results of 590 LHM and EBD patients were identified. Odds ratio (OR) was 2.20 at 12 months (95% confidence interval: 1.18-4.09; P = 0.01); 5.06 at 24 months (2.61-9.80; P < 0.00001) and 29.83 at 60 months (3.96-224.68; P = 0.001). LHM was also significantly superior for all time points when therapy included re-treatments [OR = 4.83 (1.87-12.50), 19.61 (5.34-71.95), and 17.90 (2.17-147.98); P <= 0.01 for all comparisons) Complication rates were not significantly different. Meta regression analysis showed that amount of dilations had a significant impact on treatment effects (P = 0.009). Every dilation (up to 3) improved treatment effect by 11.9% (2.8%-21.8%). CONCLUSIONS: In this network meta-analysis, LHM demonstrated superior short- and long-term efficacy and should be considered first-line treatment of esophageal achalasia. PMID- 24220601 TI - Estimating fatty alcohol contributions to the environment from laundry and personal care products using a market forensics approach. AB - Fatty alcohol-based surfactants are widely used in detergents and personal care products; they are typically disposed of down-the-drain and are degraded or removed during wastewater treatment. Analytical data had shown concentration and profile differences between regions of the United States. Market sales data were purchased relevant to the sampling dates. In combination with analysis of the fatty alcohol profiles in the top selling products, the influent profiles were reconstructed and compared to the whole U.S. sales data. The per capita usage rate for fatty alcohols through these 4000+ top selling products was 4.9 g per day, with 88% arising from liquid laundry detergents and hand dish detergents. This extrapolates to a national usage of 185,000 tonnes per year. There were significant differences in the purchasing habits of the inhabitants across the four regions sampled, although this had minimal impact on the fatty alcohol profile which was dominated by the C12 moiety. The U.S. market was also dominated by petrochemically-sourced chemicals. This market forensics approach using purchased sales data was able to extend our knowledge of the fate of these chemicals without a major (expensive) sampling and analytical campaign. PMID- 24220599 TI - Targeting of white matter tracts with transcranial magnetic stimulation. AB - BACKGROUND: TMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting. OBJECTIVE/METHODS: Here, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM). RESULTS: As expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle. CONCLUSIONS: Diffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS. PMID- 24220602 TI - Automated Risk Assessment for Stroke in Atrial Fibrillation (AURAS-AF)--an automated software system to promote anticoagulation and reduce stroke risk: study protocol for a cluster randomised controlled trial. AB - BACKGROUND: Patients with atrial fibrillation (AF) are at significantly increased risk of stroke. Oral anticoagulants (OACs) substantially reduce this risk, with gains seen across the spectrum of baseline risk. Despite the benefit to patients, OAC prescribing remains suboptimal in the United Kingdom (UK). We will investigate whether an automated software system, operating within primary care electronic medical records, can improve the management of AF by identifying patients eligible for OAC therapy and increasing uptake of this treatment. METHODS/DESIGN: We will conduct a cluster randomised controlled trial, involving general practices using the Egton Medical Information Systems (EMIS) Web clinical system. We will randomise practices to use an electronic software tool or to continue with usual care. The tool will a) produce (and continually refresh) a list of patients with AF who are eligible for OAC therapy--practices will invite these patients to discuss therapy at the start of the trial--and b) generate electronic screen reminders in the medical records of those eligible, appearing throughout the trial. The software will run for 6 months in 23 intervention practices. A total of 23 control practices will manage their AF register in line with the usual care offered. The primary outcome is change in proportion of eligible patients with AF who have been prescribed OAC therapy after six months. Secondary outcomes are incidence of stroke, transient ischaemic attack, other major thromboembolism, major haemorrhage and reports of inappropriate OAC prescribing in the data collection sample--those deemed eligible for OACs. We will conduct a process evaluation in parallel with the randomised trial. We will use qualitative methods to examine patient and practitioner views of the intervention and its impact on primary care practice, including its time implications. DISCUSSION: AURAS-AF will investigate whether a simple intervention, using electronic primary care records, can improve OAC uptake in a high risk group for stroke. Given previous concerns about safety, especially surrounding inappropriate prescribing, we will also examine whether electronic reminders safely impact care in this clinical area. TRIAL REGISTRATION: http://ISRCTN 55722437. PMID- 24220603 TI - Conjugated organic framework with three-dimensionally ordered stable structure and delocalized pi clouds. AB - Covalent organic frameworks are a class of crystalline organic porous materials that can utilize pi-pi-stacking interactions as a driving force for the crystallization of polygonal sheets to form layered frameworks and ordered pores. However, typical examples are chemically unstable and lack intrasheet pi conjugation, thereby significantly limiting their applications. Here we report a chemically stable, electronically conjugated organic framework with topologically designed wire frameworks and open nanochannels, in which the pi conjugation-spans the two-dimensional sheets. Our framework permits inborn periodic ordering of conjugated chains in all three dimensions and exhibits a striking combination of properties: chemical stability, extended pi-delocalization, ability to host guest molecules and hole mobility. We show that the pi-conjugated organic framework is useful for high on-off ratio photoswitches and photovoltaic cells. Therefore, this strategy may constitute a step towards realizing ordered semiconducting porous materials for innovations based on two-dimensionally extended pi systems. PMID- 24220605 TI - T cell responses in dengue viral infections. AB - Dengue viral infections are the commonest mosquito borne viral infection in the world, affecting more than 100 countries and 390 million individuals annually. Currently, there are no effective antiviral drugs or an effective vaccine to prevent infection. A main hurdle in developing a safe and effective vaccine has been our poor understanding of the complex nature of the protective immune response in acute dengue infection and the presence of four dengue virus (DV) serotypes that are highly homologous. The role of DV specific T cells in the pathogenesis of severe clinical disease in not clear. It has been speculated that highly cross reactive T cells for the previous infecting heterologous DV serotype, which produce pro-inflammatory cytokines, contribute to disease pathogenesis. These cross reactive T cells are believed to be suboptimal in clearing the infection with the current DV-serotype. However, other studies have shown that cross-reactive DV-specific T cells are absent or present in very low frequency during acute infection, appearing only during the convalescent period in the majority of patients. Furthermore, significant apoptosis of T cells occurs in severe acute clinical disease. Overall therefore, it is unclear what role T cells play in contributing to disease pathogenesis during acute dengue infection. Existing data have been complicated by cross-reactivity in T cells assays. These findings can now be re-evaluated in the light of novel technologies to identify serotype-specific T cell responses. PMID- 24220604 TI - Exploring autistic traits in anorexia: a clinical study. AB - BACKGROUND: The objectives of this study were to explore associations between autistic traits and self-reported clinical symptoms in a population with anorexia nervosa (AN). Experimental and self-report evidence reveals similarities between AN and autism spectrum condition (ASC) populations in socio-emotional and cognitive domains; this includes difficulties with empathy, set-shifting and global processing. Focusing on these similarities may lead to better tailored interventions for both conditions. METHODS: A cross-sectional independent-groups design was employed. Participants with AN (n = 66) and typical controls (n = 66) completed self-report questionnaires including the Short (10-Item) Version Autism Spectrum Quotient (AQ-10) questionnaire (the first time this has been implemented in this population), the Eating Disorder Examination Questionnaire, the Hospital Anxiety and Depression Scale and the Work and Social Adjustment Scale. Group differences and the relationship between autistic traits and other questionnaire measures were investigated. RESULTS: The AN group had a significantly higher AQ 10 total score and a greater proportion scored above the clinical cut-off than the control group. Seven out of ten AQ-10 items significantly discriminated between groups. In the AN group, levels of autistic traits correlated with a greater self-reported anxiety and depression and a lower ability to maintain close relationships; however, eating disorder symptoms were not associated with autistic traits. CONCLUSIONS: Women with anorexia possess a greater number of autistic traits than typical women. AQ-10 items that discriminated between groups related to 'bigger picture' (global) thinking, inflexibility of thinking and problems with social interactions, suggesting that autistic traits may exacerbate factors that maintain the eating disorder rather than cause the eating disorder directly. Using screening instruments may improve understanding of patients' problems, leading to better tailoring of intervention. We conclude that further investigation of autistic traits in AN could inform new intervention approaches based on joint working between ASC and eating disorder services. PMID- 24220606 TI - In-vivo dark-field and phase-contrast x-ray imaging. AB - Novel radiography approaches based on the wave nature of x-rays when propagating through matter have a great potential for improved future x-ray diagnostics in the clinics. Here, we present a significant milestone in this imaging method: in vivo multi-contrast x-ray imaging of a mouse using a compact scanner. Of particular interest is the enhanced contrast in regions related to the respiratory system, indicating a possible application in diagnosis of lung diseases (e.g. emphysema). PMID- 24220608 TI - Morphology, differentiation and adhesion molecule expression changes of bone marrow mesenchymal stem cells from acute myeloid leukemia patients. AB - Bone marrow mesenchymal stem cells (BMSCs) have been identified as an important component of the hematopoietic stem cell (HSC) niche, which is essential for the maintenance of HSCs. HSC niche alternation has been considered to be the main cause of acute myeloid leukemia (AML). However, little is known with regard to BMSC alteration in AML patients. BMSCs were collected from 10 AML patients and 13 controls in order to examine the morphology, differentiation and adhesion molecule expression changes. It was observed that primary BMSCs from AML patients exhibited aberrant morphologies compared with those from the controls. Prior to adipogenic differentiation, the mRNA and protein levels of the lipid marker gene lipoprotein lipase, from the BMSCs of AML patients, were significantly higher. lipid drops were present early during differentiation in the BMSCs of AML patients and exhibited greater numbers later. Following adipogenic differentiation, the mRNA level of E-cadherin in the BMSCs of AML patients was significantly lower than that identified in the BMSCs of the control groups. Following osteogenic induction, the mRNA level of E-cadherin in the BMSCs of AML patients was significantly higher than in the controls. Therefore BMSCs from the AML patients exhibited irregular morphology, tendency to pre-differentiate to adipocytes and different adhesion molecule expression following differentiation. These differences may further our understanding of the HSC niche in the pathological condition. PMID- 24220607 TI - Nonselective inhibition of prostaglandin-endoperoxide synthases by naproxen ameliorates acute or chronic liver injury in animals. AB - The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation is directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of physiological cytoprotective factors in nonparenchymal liver cells. Such drug-induced release of endogenous cytoprotectants will advance therapeutic development for hepatic injury. PMID- 24220609 TI - Influence of the immunogenetic KIR and HLA systems on long-term renal transplant outcome. AB - BACKGROUND: Numerous studies have established the importance of innate immunity, particularly natural killer (NK) cells, in transplantation tolerance. NK cells express killer cell immunoglobulin-like receptors (KIRs) on their surface. By recognizing and binding major histocompatibility complex class I antigens, KIRs prevent autologous cell killing and promote lysis of non-self antigen-presenting cells. This study investigated the role of 16 KIR genes and donor-recipient KIR/HLA combinations on 5-year outcomes in a population of deceased donor kidney transplant recipients. MATERIAL/METHODS: We genotyped 126 renal transplant patients and their donors for HLA A, B, C, DR, and KIR genes. Patients underwent standardized transplantation and immunosuppressive protocols and were followed-up for 5 years. Graft function was evaluated by serum creatinine level and glomerular filtration rate calculated using the 4-variable modification of diet in renal disease (MDRD) equation. RESULTS: The presence of KIR2DS3 in the recipients was associated with better graft function indexes over time (p<0.05), but this effect was not confirmed by multivariate analysis. Conversely, the presence KIR2DS3 in the recipients combined with the presence of its HLA ligand in the donor had a detrimental effect on the trends of serum creatinine levels and eGFR trends, also confirmed by multivariate analysis. Kidney transplant recipients negative for the KIR2DL1 gene displayed higher creatinine levels after 5 years. Lastly, transplantation of HLA-A3/A11-negative donor kidneys into KIR3DL2-positive patients exerted a protective effect in terms of 5-years outcome (p<0.05). CONCLUSIONS: The present study demonstrates an important role of the KIR immunogenetic system in the long-term immune response to kidney transplantation. PMID- 24220611 TI - Reprint: 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. PMID- 24220610 TI - Identification and management of toxicological hazards of street foods in developing countries. AB - Street food vending represents an important food security strategy for low-income communities worldwide. However, no comprehensive risk analysis framework yet exists as regards specific aspects of chemical/toxicological hazards in street foods. Indeed, all steps of street food production and vending can be vulnerable, from the selection of raw materials, through to the storage and preparation of meals and even the vending site, often exposed to urban pollutants. Relevant examples are cheap ingredients with illegal or undesirable residues, substances arising in poorly stored commodities (e.g., mycotoxins, histamine in scombroid fish), metals leaching from cookware, and process contaminants such as PAHs and acrylamide. As a consequence, greater awareness and preventive measures need to be implemented for coping with chemical/toxicological risk factors in a systematic and effective way. This review proposes specific points of attention for street foods preparation and vending with related hazard-tailored actions. The proposed measures in street food vending could integrate the prevention of biological risk factors, in order to promote comprehensive and up-to-date consumer safety. PMID- 24220612 TI - Gait analysis in orthopedic foot and ankle surgery--topical review, part 1: principles and uses of gait analysis. AB - Gait analysis, the systematic study of human walking, is a field that has been studied for well over 100 years. With the technological and scientific advancements of the last several decades, there has been substantial improvement in our understanding of the mechanics of human walking. Particularly important has been the advancement in understanding of the differences between normal and pathological gait. The purpose of this paper is to review the principles of gait analysis, with a particular focus on the underlying methods and science. This will assist orthopedic foot and ankle surgeons in better understanding the methods and meaning of gait research and the publications that commonly appear in the orthopedic foot and ankle surgery literature. LEVEL OF EVIDENCE: Level V, expert opinion. PMID- 24220613 TI - Adiabatic Rotor-Echo-Short-Pulse-Irradiation mediated cross-polarization. AB - We present a new dipolar recoupling method for efficient and robust heteronuclear polarization transfer in solid-state NMR under magic-angle-spinning (MAS) conditions. The method combines the recent (RESPIRATION)CP method with a modulation of the amplitude of the rotor-synchronized pulses at one of the involved rf channels through the recoupling condition. In this manner, it is possible to achieve high transfer efficiencies while maintaining robustness towards rf-field inhomogeneities and resonance offsets. The performance of the so called adiabatic-(RESPIRATION)CP experiment is demonstrated numerically and experimentally using uniformly (13)C,(15)N-labeled samples of alanine and ubiquitin. In particular for cases with relatively high rf inhomogeneity, the scheme offers advantages over the commonly used dipolar recoupling pulse sequences. PMID- 24220614 TI - Constant gradient PFG sequence and automated cumulant analysis for quantifying dispersion in flow through porous media. AB - This paper describes a new variant of established stimulated echo pulse sequences, and an analytical method for determining diffusion or dispersion coefficients for Gaussian or non-Gaussian displacement distributions. The unipolar displacement encoding PFGSTE sequence uses trapezoidal gradient pulses of equal amplitude g and equal ramp rates throughout while sampling positive and negative halves of q-space. Usefully, the equal gradient amplitudes and gradient ramp rates help to reduce the impact of experimental artefacts caused by residual amplifier transients, eddy currents, or ferromagnetic hysteresis in components of the NMR magnet. The pulse sequence was validated with measurements of diffusion in water and of dispersion in flow through a packing of spheres. The analytical method introduced here permits the robust determination of the variance of non Gaussian, dispersive displacement distributions. The noise sensitivity of the analytical method is shown to be negligible, using a demonstration experiment with a non-Gaussian longitudinal displacement distribution, measured on flow through a packing of mono-sized spheres. PMID- 24220615 TI - Patterns of infection in patients with myelodysplastic syndromes and acute myeloid leukemia receiving azacitidine as salvage therapy. Implications for primary antifungal prophylaxis. AB - Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens. PMID- 24220616 TI - A post hoc sensitivity analysis of survival probabilities in a multinational phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia. AB - BACKGROUND: In a multicenter, randomized, open-label phase III study, patients >= 65 years with newly diagnosed AML received decitabine 20 mg/m(2) once daily for 5 days every 4 weeks (n = 242) or treatment choice (supportive care or cytarabine 20 mg/m(2) once daily for 10 days every 4 weeks; n = 243). Decitabine use demonstrated greater response rates (P = .001) and OS data favored decitabine. PATIENTS AND METHODS: In a post hoc sensitivity analysis of mature data of patients in the intent-to-treat population (N = 485), OS at 3, 6, 12, 18, and 24 months after randomization was estimated for each arm using Kaplan-Meier methods. Age, cytogenetic risk, and Eastern Cooperative Oncology Group performance status were used as stratification factors in the Cox regression model to estimate the hazard ratio. RESULTS: A survival advantage was seen with decitabine at each cutoff time point; hazard ratios for OS for decitabine vs. treatment choice were 0.83, 0.71, 0.83, 0.80, and 0.79 at 3, 6, 12, 18, and 24 months, respectively. A trend toward improved OS with decitabine was observed at fixed time points over 2 years. CONCLUSION: Decitabine should be considered as a treatment option for older patients with AML and poor prognostic risk factors. PMID- 24220617 TI - A case of primary cardiac lymphoma showing isolated central nervous system relapse. PMID- 24220618 TI - Large-cell transformation of mycosis fungoides occurring at the site of previously treated cutaneous B-cell lymphoma. PMID- 24220619 TI - Pure erythroid leukemia presenting in a HIV-positive patient. PMID- 24220620 TI - Coexistence of myeloproliferative neoplasm and plasma-cell dyscrasia. AB - INTRODUCTION: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and are characterized by clonal proliferation of hematopoietic cells in the bone marrow. There are numerous case reports and reviews reporting patients with coexisting MPN and plasma-cell disease such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). METHODS: We report 15 patients treated at our institution over a 5-year period (January 2008 to December 2012) with a diagnosis of both an MPN and MGUS or MM. We also reviewed and summarized published case reports and studies describing the coexistence of these two disease entities. RESULTS: Most patients (12/15) had an MPN diagnosis made before or at the same time as the MGUS/MM diagnosis. Eventually, 2 patients developed a lymphoid leukemia, 1 patient developed lymphoma, and 1 patient developed acute myeloid leukemia, raising the question of whether patients with coexistence of myeloid- and lymphoid-derived neoplasms are more prone to leukemic or lymphomatous transformation. We did not find any treatment-related effect that could have contributed to the development of coexisting MGUS or MM and MPN. Of the 7 patients with an abnormal karyotype, 3 patients had trisomy 8. CONCLUSION: At present, management strategies are aimed at treating the MPN and regularly monitoring the MGUS for transformation to an overt plasma-cell malignancy. However, for patients who develop overt MM, management is focused more on treating the myeloma and monitoring the MPN. It has not yet been definitively shown that these 2 entities arise from a common ancestor hematopoietic stem cell. PMID- 24220621 TI - Chemopreventative effects of tetrahydrocurcumin on human diseases. AB - Chemoprevention is a relatively new and promising strategy to prevent human degenerative diseases, including cancer, and is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the progress of human diseases. Tetrahydrocurcumin (THC) is a major metabolite of curcumin (extracted from the roots of the Curcuma longa Linn). THC has been demonstrated to prevent oxidative stress and inflammation, to act against neurodegeneration, and to possess anti-cancer activity. In this review, we summarize the current knowledge and underlying molecular mechanisms of the chemopreventative activities of THC and its potential effects on the development of various human diseases. PMID- 24220622 TI - Tumor necrosis factor alpha induces epithelial-mesenchymal transition and promotes metastasis via NF-kappaB signaling pathway-mediated TWIST expression in hypopharyngeal cancer. AB - Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer metastasis. Tumor necrosis factor alpha (TNFalpha) can induce cancer invasion and metastasis associated with EMT. However, the underlying mechanisms are not entirely clear. Therefore, we investigated whether TNFalpha has an effect on EMT and invasion and metastasis in human hypopharyngeal cancer FaDu cells, and further explored the potential mechanisms. In the present study, we demonstrated that TNFalpha induced EMT in FaDu cells and promoted FaDu cell migration and invasion. TNFalpha-induced EMT was characterized by a change from well organized cell-cell adhesion and cell polarity to loss of cell-cell contacts, cell scattering and increased expression of vimentin and N-cadherin accompanied by a decrease in E-cadherin. Furthermore, we found that p65 translocated to the nucleus after TNFalpha stimulation and increased the nuclear expression of TWIST. We demonstrated that TNFalpha treatment also increased the expression of TWIST by activating the NF-kappaB signaling pathway. While p65 was inhibited by siRNA-65 or BAY11-7082 (inhibitor of NF-kappaB), TWIST expression was also decreased. Therefore, we conclude that TNFalpha induces EMT and promotes metastasis via NF kappaB signaling pathway-mediated TWIST expression in hypopharyngeal cancer. PMID- 24220623 TI - Human infants' learning of social structures: the case of dominance hierarchy. AB - We tested 15-month-olds' capacity to represent social-dominance hierarchies with more than two agents. Our results showed that infants found it harder to memorize dominance relations that were presented in an order that hindered the incremental formation of a single structure (Study 1). These results suggest that infants attempt to build structures incrementally, relation by relation, thereby simplifying the complex problem of recognizing a social structure. Infants also found circular dominance structures harder to process than linear dominance structures (Study 2). These expectations about the shape of structures may facilitate learning. Our results suggest that infants attempt to represent social structures composed of social relations. They indicate that human infants go beyond learning about individual social partners and their respective relations and form hypotheses about how social groups are organized. PMID- 24220624 TI - Symmetry in cold-to-hot and hot-to-cold valuation gaps. AB - Individuals commonly mispredict their future preferences when they make decisions in a visceral state different from their anticipated state at consumption. In the research reported here, we asked subjects to bid on different foods while exogenously varying their hunger levels at the time of decision and at the time of consumption. This procedure allowed us to test whether cold-to-hot and hot-to cold gaps are symmetric in size and driven by similar mechanisms. We found that the effect size was symmetric: Hungry subjects overbid 20c for a snack they would eat later when they were satiated, and satiated subjects underbid 19c for a snack they would eat later when they were hungry. Furthermore, we found evidence that these gaps were driven by symmetric mechanisms that operate on the evaluation of visceral features of food, such as taste, as opposed to more cognitive features, such as healthiness. PMID- 24220625 TI - Parents are slightly happier than nonparents, but causality still cannot be inferred: a reply to Bhargava, Kassam, and Loewenstein (2014). PMID- 24220626 TI - War's enduring effects on the development of egalitarian motivations and in-group biases. AB - In suggesting that new nations often coalesce in the decades following war, historians have posed an important psychological question: Does the experience of war generate an enduring elevation in people's egalitarian motivations toward their in-group? We administered social-choice tasks to more than 1,000 children and adults differentially affected by wars in the Republic of Georgia and Sierra Leone. We found that greater exposure to war created a lasting increase in people's egalitarian motivations toward their in-group, but not their out-groups, during a developmental window starting in middle childhood (around 7 years of age) and ending in early adulthood (around 20 years of age). Outside this window, war had no measurable impact on social motivations in young children and had only muted effects on the motivations of older adults. These "war effects" are broadly consistent with predictions from evolutionary approaches that emphasize the importance of group cooperation in defending against external threats, though they also highlight key areas in need of greater theoretical development. PMID- 24220627 TI - The ground side of an object: perceived as shapeless yet processed for semantics. AB - Traditional theories of perception posit that only objects access semantics; abutting, patently shapeless grounds do not. Surprisingly, this assumption has been untested until now. In two experiments, participants classified silhouettes as depicting meaningful real-world or meaningless novel objects while event related potentials (ERPs) were recorded. The borders of half of the novel objects suggested portions of meaningful objects on the ground side. Participants were unaware of these meaningful objects because grounds are perceived as shapeless. In Experiment 1, in which silhouettes were presented twice, N400 ERP repetition effects indicated that semantics were accessed for novel silhouettes that suggested meaningful objects in the ground and for silhouettes that depicted real world objects, but not for novel silhouettes that did not suggest meaningful objects in the ground. In Experiment 2, repetition was manipulated via matching prime words. This experiment replicated the effect observed in Experiment 1. These experiments provide the first neurophysiological evidence that semantic access can occur for the apparently shapeless ground side of a border. PMID- 24220628 TI - A reassessment of the defense of parenthood. PMID- 24220629 TI - The new statistics: why and how. AB - We need to make substantial changes to how we conduct research. First, in response to heightened concern that our published research literature is incomplete and untrustworthy, we need new requirements to ensure research integrity. These include prespecification of studies whenever possible, avoidance of selection and other inappropriate data-analytic practices, complete reporting, and encouragement of replication. Second, in response to renewed recognition of the severe flaws of null-hypothesis significance testing (NHST), we need to shift from reliance on NHST to estimation and other preferred techniques. The new statistics refers to recommended practices, including estimation based on effect sizes, confidence intervals, and meta-analysis. The techniques are not new, but adopting them widely would be new for many researchers, as well as highly beneficial. This article explains why the new statistics are important and offers guidance for their use. It describes an eight-step new-statistics strategy for research with integrity, which starts with formulation of research questions in estimation terms, has no place for NHST, and is aimed at building a cumulative quantitative discipline. PMID- 24220630 TI - Regulation of Cu-Zn superoxide dismutase on SCN2A in SH-SY5Y cells as a potential therapy for temporal lobe epilepsy. AB - In order to evaluate SCN2A as a candidate gene for epileptic susceptibility and the use of a Cu-Zn superoxide dismutase (SOD) supplement as a potential therapy for epilepsy, SCN2A expression in the cortex and the correlation between SCN2A and Cu-Zn SOD in SH-SY5Y cells were examined. SCN2A expression and the concentration of Cu-Zn SOD in the cerebral cortexes of patients with primary and secondary temporal lobe epilepsy and normal brain cortex tissues were detected. By transfecting SH-SY5Y cells, the expression of SCN2A and the concentration of Cu-Zn SOD was analyzed and the single-cell patch clamp technique was employed in order to investigate the changes in sodium ion levels following SCN2A knockdown. SCN2A level restoration was also investigated with a Cu-Zn SOD supplement using an expression study and evaluated the changes in sodium ion levels following SCN2A knockdown. SCN2A expression and Cu-Zn SOD concentration decreased in the epileptic cerebral cortex. Following SCN2A knockdown, the concentration of Cu-Zn SOD declined and the si-SCN2A vector group showed a repeated discharge. Furthermore, the Cu-Zn SOD concentration was capable of restoring the expression of SCN2A following SCN2A knockdown in SH-SY5Y cells and the overexpression of Cu Zn SOD prevented the repeated discharge caused by si-SCN2A. The results indicated that there is a low expression of SCN2A and Cu-Zn SOD in the epileptic cerebral cortex and provided novel insights into potential therapies for temporal lobe epilepsy. PMID- 24220631 TI - Two herbivore-induced cytochrome P450 enzymes CYP79D6 and CYP79D7 catalyze the formation of volatile aldoximes involved in poplar defense. AB - Aldoximes are known as floral and vegetative plant volatiles but also as biosynthetic intermediates for other plant defense compounds. While the cytochrome P450 monooxygenases (CYP) from the CYP79 family forming aldoximes as biosynthetic intermediates have been intensively studied, little is known about the enzymology of volatile aldoxime formation. We characterized two P450 enzymes, CYP79D6v3 and CYP79D7v2, which are involved in herbivore-induced aldoxime formation in western balsam poplar (Populus trichocarpa). Heterologous expression in Saccharomyces cerevisiae revealed that both enzymes produce a mixture of different aldoximes. Knockdown lines of CYP79D6/7 in gray poplar (Populus * canescens) exhibited a decreased emission of aldoximes, nitriles, and alcohols, emphasizing that the CYP79s catalyze the first step in the formation of a complex volatile blend. Aldoxime emission was found to be restricted to herbivore-damaged leaves and is closely correlated with CYP79D6 and CYP79D7 gene expression. The semi-volatile phenylacetaldoxime decreased survival and weight gain of gypsy moth (Lymantria dispar) caterpillars, suggesting that aldoximes may be involved in direct defense. The wide distribution of volatile aldoximes throughout the plant kingdom and the presence of CYP79 genes in all sequenced genomes of angiosperms suggest that volatile formation mediated by CYP79s is a general phenomenon in the plant kingdom. PMID- 24220632 TI - The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 activates FLOWERING LOCUS C transcription via chromatin remodeling under short term cold stress in Arabidopsis. AB - Exposure to short-term cold stress delays flowering by activating the floral repressor FLOWERING LOCUS C (FLC) in Arabidopsis thaliana. The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1) negatively regulates cold responses. Notably, HOS1-deficient mutants exhibit early flowering, and FLC expression is suppressed in the mutants. However, it remains unknown how HOS1 regulates FLC expression. Here, we show that HOS1 induces FLC expression by antagonizing the actions of FVE and its interacting partner histone deacetylase 6 (HDA6) under short-term cold stress. HOS1 binds to FLC chromatin in an FVE-dependent manner, and FVE is essential for the HOS1-mediated activation of FLC transcription. HOS1 also interacts with HDA6 and inhibits the binding of HDA6 to FLC chromatin. Intermittent cold treatments induce FLC expression by activating HOS1, which attenuates the activity of HDA6 in silencing FLC chromatin, and the effects of intermittent cold are diminished in hos1 and fve mutants. These observations indicate that HOS1 acts as a chromatin remodeling factor for FLC regulation under short-term cold stress. PMID- 24220633 TI - Towards breeding strong but fine cotton fibers with a little help from WLIM1a. PMID- 24220635 TI - Biologically enhanced cathode design for improved capacity and cycle life for lithium-oxygen batteries. AB - Lithium-oxygen batteries have a great potential to enhance the gravimetric energy density of fully packaged batteries by two to three times that of lithium ion cells. Recent studies have focused on finding stable electrolytes to address poor cycling capability and improve practical limitations of current lithium-oxygen batteries. In this study, the catalyst electrode, where discharge products are deposited and decomposed, was investigated as it has a critical role in the operation of rechargeable lithium-oxygen batteries. Here we report the electrode design principle to improve specific capacity and cycling performance of lithium oxygen batteries by utilizing high-efficiency nanocatalysts assembled by M13 virus with earth-abundant elements such as manganese oxides. By incorporating only 3-5 wt% of palladium nanoparticles in the electrode, this hybrid nanocatalyst achieves 13,350 mAh g(-1)(c) (7,340 mAh g(-1)(c+catalyst)) of specific capacity at 0.4 A g(-1)(c) and a stable cycle life up to 50 cycles (4,000 mAh g(-1)(c), 400 mAh g(-1)(c+catalyst)) at 1 A g(-1)(c). PMID- 24220634 TI - The dual functions of WLIM1a in cell elongation and secondary wall formation in developing cotton fibers. AB - LIN-11, Isl1 and MEC-3 (LIM)-domain proteins play pivotal roles in a variety of cellular processes in animals, but plant LIM functions remain largely unexplored. Here, we demonstrate dual roles of the WLIM1a gene in fiber development in upland cotton (Gossypium hirsutum). WLIM1a is preferentially expressed during the elongation and secondary wall synthesis stages in developing fibers. Overexpression of WLIM1a in cotton led to significant changes in fiber length and secondary wall structure. Compared with the wild type, fibers of WLIM1a overexpressing plants grew longer and formed a thinner and more compact secondary cell wall, which contributed to improved fiber strength and fineness. Functional studies demonstrated that (1) WLIM1a acts as an actin bundler to facilitate elongation of fiber cells and (2) WLIM1a also functions as a transcription factor to activate expression of Phe ammonia lyase-box genes involved in phenylpropanoid biosynthesis to build up the secondary cell wall. WLIM1a localizes in the cytosol and nucleus and moves into the nucleus in response to hydrogen peroxide. Taken together, these results demonstrate that WLIM1a has dual roles in cotton fiber development, elongation, and secondary wall formation. Moreover, our study shows that lignin/lignin-like phenolics may substantially affect cotton fiber quality; this finding may guide cotton breeding for improved fiber traits. PMID- 24220636 TI - Metabolic inflammation exacerbates dopaminergic neuronal degeneration in response to acute MPTP challenge in type 2 diabetes mice. AB - Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra. Increasing epidemiological evidence has indicated that type 2 diabetes (T2D) may be implicated in the pathogenesis of PD. However, the exact association and the underlying mechanism remain unclear. In the present study, ob/ob and db/db mice, the well accepted T2D models, were acutely treated with MPTP (1-methyl-4-phenyl 1, 2, 3, 6-tetrahydropyridine) to mimic PD-like neural injury. We found that insulin signaling impairment occurred not only in pancreas and livers, but also in the midbrain of ob/ob and db/db mice. Notably, the expressions of monomeric and oligomeric alpha-synuclein as well as endoplasmic reticulum stress markers (CHOP and GRP78) were significantly upregulated in both pancreas and midbrain of T2D mice, accompanied by the increased activation of NLRP3 inflammasomes to produce excess IL-1beta. Furthermore, we found that acute MPTP administration aggravated the loss of dopaminergic neurons and increased the activation of glial cells in the substantia nigra of db/db mice. Collectively, these findings demonstrate that alpha-synuclein accumulation and neuroinflammation are aggravated in the midbrain of T2D mice and T2D mice are more susceptible to the neurotoxicity induced by MPTP. Our study indicates that metabolic inflammation exacerbates DA neuronal degeneration in the progress of PD, which will provide a novel insight into the etiology of PD. PMID- 24220637 TI - Validation of doubled haploid plants by enzymatic mismatch cleavage. AB - BACKGROUND: Doubled haploidy is a fundamental tool in plant breeding as it provides the fastest way to generate populations of meiotic recombinants in a genetically fixed state. A wide range of methods has been developed to produce doubled haploid (DH) plants and recent advances promise efficient DH production in otherwise recalcitrant species. Since the cellular origin of the plants produced is not always certain, rapid screening techniques are needed to validate that the produced individuals are indeed homozygous and genetically distinct from each other. Ideal methods are easily implemented across species and in crops where whole genome sequence and marker resources are limited. RESULTS: We have adapted enzymatic mismatch cleavage techniques commonly used for TILLING (Targeting Induced Local Lesions IN Genomes) for the evaluation of heterozygosity in parental, F1 and putative DH plants. We used barley as a model crop and tested 26 amplicons previously developed for TILLING. Experiments were performed using self-extracted single-strand-specific nuclease and standard native agarose gels. Eleven of the twenty-six tested primers allowed unambiguous assignment of heterozygosity in material from F1 crosses and loss of heterozygosity in the DH plants. Through parallel testing of previously developed Simple Sequence Repeat (SSR) markers, we show that 3/32 SSR markers were suitable for screening. This suggests that enzymatic mismatch cleavage approaches can be more efficient than SSR based screening, even in species with well-developed markers. CONCLUSIONS: Enzymatic mismatch cleavage has been applied for mutation discovery in many plant species, including those with little or no available genomic DNA sequence information. Here, we show that the same methods provide an efficient system to screen for the production of DH material without the need of specialized equipment. This gene target based approach further allows discovery of novel nucleotide polymorphisms in candidate genes in the parental lines. PMID- 24220638 TI - Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice. AB - AIM: To characterize the phenotype of Akt2/low-density-lipoprotein receptor double knockout (dKO) (Akt2/LDLr dKO) mice with respect to insulin resistance and features of atherosclerotic plaque progression. METHODS AND RESULTS: Metabolic profile and atherosclerotic plaque progression were compared between LDLr KO mice and Akt2/LDLr dKO mice. Total cholesterol, glucose, and insulin levels were significantly higher and oral glucose tolerance test (GTT) was more impaired in Akt2/LDLr dKO mice than in LDLr KO mice. Although atherosclerotic plaques at both the carotid artery and the aortic root of Akt2/LDLr dKO mice were significantly smaller (P < 0.05) compared with LDLr KO controls, plaque composition in these mice was more complex, showing 34-50% reduced collagen content (P < 0.01), 1.4 fold larger necrotic cores (P < 0.05) and six-fold more TUNEL-positive cells (P < 0.01). In situ zymography revealed a more than two-fold higher gelatinolytic activity in Akt2/LDLr dKO mice (P < 0.05). In vitro analyses showed that deletion of Akt2 caused decreased migration, proliferation, and collagen content of vascular smooth muscle cells (VSMCs) and disturbed the balance of metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) mRNA expression in macrophages and VSMCs. CONCLUSION: Akt2/LDLr dKO mice develop insulin resistance and complex atherosclerotic lesions. These phenotypic characteristics make Akt2/LDLr dKO mice an interesting mouse model to study the effects of insulin resistance on the development and progression of atherosclerosis. PMID- 24220639 TI - Hypoxic mesenchymal stem cells engraft and ameliorate limb ischaemia in allogeneic recipients. AB - AIMS: Local injection of stem cells or endothelial progenitors directly into the ischaemic tissue remains an option for the management of arterial occlusion. Bone marrow-derived mesenchymal stem cells (MSCs) represent a promising alternative autologous cell source for ischaemic limb cell therapy. However, methods for applying MSCs in allogeneic transplantation remain to be developed. The purpose of this study was to evaluate the therapeutic potential of MSCs cultured under a different environment in ameliorating limb ischaemia in allogeneic recipients. METHODS AND RESULTS: Here, we demonstrated that hypoxic MSCs from B6 mice ameliorate limb ischaemia of Balb/c mice compared with normoxic MSCs. We also demonstrated that hypoxic MSCs have an increased ability to engraft in allogeneic recipients by reducing natural killer (NK) cytotoxicity and decrease the accumulation of host-derived NK cells when transplanted in vivo. These allogeneic hypoxic MSCs gave rise to CD31+ endothelial cells and alpha-smooth muscle actin (SMA)+ and desmin+ muscle cells, thereby enhancing angiogenesis and restoring muscle structure. Moreover, application of anti-NK antibodies together with normoxic MSCs enhanced angiogenesis and prevented limb amputation in allogeneic recipients with limb ischaemia. CONCLUSION: These results strongly suggest that hypoxic MSCs are intrinsically immunoprivileged and can serve as a 'universal donor cell' for treating cardiovascular diseases. PMID- 24220640 TI - NFAT signalling and the differentiation of coronary smooth muscle cells. PMID- 24220641 TI - Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine. AB - There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI-FI agents. PMID- 24220642 TI - Leptin increases mitotic index and regeneration ratio in hepatectomized rats. AB - BACKGROUND: The aim of this study was to evaluate the potential effect of intraperitoneal administration of leptin on the hepatic regeneration and the mitotic index. MATERIAL AND METHODS: 56 Sprague-Dawley rats were divided into 7 groups each containing 8 rats. Group 1 was evaluated as the sham group and no surgical procedure was performed on animals. The rats in groups 2, 3, and 4 (named C24, C48, C72, respectively) were given intraperitoneal injection of 2 ml/kg normal saline 60 minutes before the surgical procedure consisting of laparotomy and 70% hepatectomy. These groups were used as controls at 24, 48, and 72 hours. The rats in groups 5, 6, and 7 (named L24, L48, and L72, respectively) were given intraperitoneal injection of 20 ug/kg doses of recombinant mouse leptin 60 minutes before the same surgical procedure. These groups were evaluated as the experiment groups at 24, 48, and 72 hours. Blood samples were collected for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the remaining tissue samples were obtained for liver histopathology, regeneration rate, and mitotic index (MI). The weights of the remaining livers were also noted. RESULTS: The values of AST and ALT were higher in the groups that were administered leptin and they had significantly higher mitotic index than the other groups. Leptin also significantly increased the regeneration ratio as compared to the control group. The weights of the remaining livers were also higher in the leptin groups. CONCLUSIONS: Intraperitoneal administration of leptin was observed to increase liver regeneration and mitotic rate in 70% hepatectomized rats. PMID- 24220643 TI - Salmonella osteomyelitis of the calcaneum bone in an immunocompetent child. AB - Salmonella osteomyelitis occurs infrequently in healthy children and can manifest in the subacute form. This condition has only been reported in few cases previously. We report the first case of primary subacute haematogenous osteomyelitis of the calcaneum in a healthy 12-year-old child. The patient made uneventful recovery following surgical drainage and antibiotic therapy. Histology of the tissue biopsy confirmed a diagnosis of Salmonella livingstone infection. Although the diagnosis of Salmonella osteomyelitis of the calcaneum can be difficult to establish, it should be considered as an aetiological factor even in healthy children. PMID- 24220644 TI - Association of violence with emergence of persecutory delusions in untreated schizophrenia. AB - OBJECTIVE: Psychosis is considered an important risk factor for violence, but studies show inconsistent results. The mechanism through which psychotic disorders influence violence also remains uncertain. The authors investigated whether psychosis increased the risk of violent behavior among released prisoners and whether treatment reduced this risk. They also explored whether active symptoms of psychosis at the time of violent behavior explained associations between untreated psychosis and violence. METHOD: The U.K. Prisoner Cohort Study is a prospective longitudinal study of prisoners followed up in the community after release. Adult male and female offenders serving sentences of 2 or more years for a sexual or violent offense were classified into four groups: no psychosis (N=742), schizophrenia (N=94), delusional disorder (N=29), and drug induced psychosis (N=102). Symptoms of psychosis, including hallucinations, thought insertion, strange experiences, and delusions of persecution, were measured before and after release. Information on violence between release and follow-up was collected through self-report and police records. RESULTS: Schizophrenia was associated with violence but only in the absence of treatment (odds ratio=3.76, 95% CI=1.39-10.19). Untreated schizophrenia was associated with the emergence of persecutory delusions at follow-up (odds ratio=3.52, 95% CI=1.18 10.52), which were associated with violence (odds ratio=3.68, 95% CI=2.44-5.55). The mediating effects of persecutory delusions were confirmed in mediation analyses (beta=0.02, 95% CI=0.01-0.04). CONCLUSIONS: The results indicate that the emergence of persecutory delusions in untreated schizophrenia explains violent behavior. Maintaining psychiatric treatment after release can substantially reduce violent recidivism among prisoners with schizophrenia. Better screening and treatment of prisoners is therefore essential to prevent violence. PMID- 24220645 TI - Socioeconomic patterns in use of private and public health services in Spain and Britain: implications for equity in health care. AB - This paper estimates the pattern of private and public physician visits and hospitalisation by socioeconomic position in two countries in which private healthcare expenditure constitutes a different proportion of the total amount spent on health care: Britain and Spain. Private physician visits and private hospitalisations were quantitatively more important in Spain than in Britain. In both countries, the use of private services showed a direct socioeconomic gradient. In Spain, the use of public GPs and public specialists tends to favour the worst-off, but no significant differences were observed in public hospitalisation. In Britain, with some exceptions, no significant socioeconomic differences were observed in the use of public health care services. The different pattern observed in the use of public specialist services may be due to the high frequency of visits to private specialists in Spain. PMID- 24220646 TI - Selective responses of enzymes in the two parallel pathways of rosmarinic acid biosynthetic pathway to elicitors in Salvia miltiorrhiza hairy root cultures. AB - Rosmarinic acid and salvianolic acid B are two important phenolic compounds with therapeutic properties in Salvia miltiorrhiza Bunge. The biosynthesis of rosmarinic acid is initiated by two parallel pathways, namely the phenylpropanoid pathway and the tyrosine-derived pathway. Salvianolic acid B is a structural dimer of rosmarinic acid and is believed to be derived from rosmarinic acid. In the current study, methyl jasmonate (MeJA) and hyphal extracts from fungi were used as elicitors to examine the relationship between enzymes in the two parallel pathways and accumulation of phenolic compounds in S. miltiorrhiza hairy root cultures. The results showed that accumulations of rosmarinic acid, salvianolic acid B and total phenolics were enhanced by MeJA while suppressed by fugal extracts. Responses of enzymes in the tyrosine-derived pathway, at both the gene transcript and enzyme activity levels, showed a better consistency with alterations of phenolic compounds content after the two elicitors treated. Our study implied that compared with enzymes in the phenylpropanoid pathway, enzymes in the tyrosine-derived pathway are more correlated to rosmarinic acid and salvianolic acid B biosynthesis in S. miltiorrhiza hairy roots. PMID- 24220647 TI - DeCon: a tool to detect emotional concordance in multivariate time series data of emotional responding. AB - The occurrence of concordance among different response components during an emotional episode is a key feature of several contemporary accounts and definitions of emotion. Yet, capturing such response concordance in empirical data has proven to be elusive, in large part because of a lack of appropriate statistical tools that are tailored to measure the intricacies of response concordance in the context of data on emotional responding. In this article, we present a tool we developed to detect two different forms of response concordance response patterning and synchronization-in multivariate time series data of emotional responding, and apply this tool to data concerning physiological responding to emotional stimuli. While the findings provide partial evidence for both response patterning and synchronization, they also show that the presence and nature of such patterning and synchronization is strongly person-dependent. PMID- 24220648 TI - Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip. AB - Circulating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this "liquid biopsy" holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50-50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients' blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer diagnosis and treatment monitoring. PMID- 24220649 TI - There is no benefit to universal carotid artery duplex screening before a major cardiac surgical procedure. AB - BACKGROUND: Perioperative stroke is a devastating complication after cardiac surgery. In an attempt to minimize this complication, many cardiac surgeons routinely preoperatively order carotid artery duplex scans to assess for significant carotid stenosis. We hypothesize that the routine screening of preoperative cardiac surgery patients with carotid artery duplex scans detects few patients who would benefit from carotid intervention or that a significant carotid stenosis reliably predicts stroke risk after cardiac surgery. METHODS: A retrospective review identified 1,499 patients who underwent cardiac surgical procedures between July 1999 and September 2010. Data collected included patient demographics, comorbidities, history of previous stroke, preoperative carotid artery duplex scan results, location of postoperative stroke, and details of carotid endarterectomy (CEA) procedures before, in conjunction with, or after cardiac surgery. Statistical methods included univariate analysis and Fisher's exact test. RESULTS: Twenty-six perioperative strokes were identified (1.7%). In the 21 postoperative stroke patients for whom there is complete carotid artery duplex scan data, 3 patients had a hemodynamically significant lesion (>70%) and 1 patient underwent unilateral carotid CEA for bilateral disease. Postoperative strokes occurred in the anterior cerebral circulation (69.2%), posterior cerebral circulation (15.4%), or both (15.4%). Patient comorbidities, preoperative carotid artery duplex scan screening velocities, or types of cardiac surgical procedure were not predictive for stroke. Thirteen patients (0.86%) underwent CEA before, in conjunction with, or after cardiac surgery. Two of these patients had symptomatic disease, 1 of whom underwent CEA before and the other after his cardiac surgery. Of the 11 asymptomatic patients, 2 underwent CEA before, 3 concurrently, and 6 after cardiac surgery. Left main disease (>=50% stenosis), previous stroke, and peripheral vascular disease were found to be statistically significant predictors of carotid revascularization. A cost analysis of universal screening resulted in an estimated net cost of $378,918 during the study period. CONCLUSIONS: The majority of postoperative strokes after cardiac surgery are not related to extracranial carotid artery disease and they are not predicted by preoperative carotid artery duplex scan screening. Consequently, universal carotid artery duplex scan screening cannot be recommended and a selective approach should be adopted. PMID- 24220650 TI - Effects of clustered comorbid conditions on walking capacity in patients with peripheral artery disease. AB - BACKGROUND: Comorbid conditions are known to increase cardiovascular risk in patients with peripheral artery disease (PAD). However, whether comorbid conditions affect walking capacity remains controversial. Previous studies have analyzed comorbidities separately, but they are known to occur in a clustered fashion in PAD patients. Therefore, the aim of this study was to analyze the influence of clustered comorbid conditions on walking capacity in PAD patients. METHODS: This cross-sectional study included 415 PAD patients (155 women and 260 men with an average age of 63 years). Claudication distance and total walking distance were assessed with the graded maximal treadmill test. Medical histories of hypertension, diabetes, cerebrovascular disease (CVD), coronary artery disease (CAD), and chronic obstructive pulmonary disease (COPD) were obtained. Binary logistic regression was carried out to analyze whether clustered comorbid conditions were associated with walking capacity. RESULTS: CVD was associated with lower total walking distance (odds ratio [OR] = 2.45; 95% confidence interval [CI]: 1.11-5.39). The cluster hypertension, diabetes, CVD, CAD, and COPD were associated with a lower claudication distance (OR = 7.63; 95% CI: 1.42 40.96). In addition, the clusters of CVD and hypertension (OR = 3.16; 95% CI: 1.38-7.23), CVD and CAD (OR = 3.46; 95% CI: 1.25-9.57), CVD, hypertension, and diabetes (OR = 11.38; 95% CI: 2.27-57.00) were associated with a lower total walking distance. CONCLUSIONS: CVD was associated with walking impairment of IC patients and in particular when CVD is clustered with other comorbid conditions. PMID- 24220651 TI - Protective effect of ocotillol against doxorubicin-induced acute and chronic cardiac injury. AB - Doxorubicin (Dox) has been clinically observed to exert marked anticancer activity. However, it is severely restricted by its associated dose-dependent cardiotoxicity, which may be attenuated by decreasing the cumulative dosage via combining with a non-toxic 'sensitizer'. We previously reported that ocotillol is capable of enhancing the antitumor activity of Dox; however, the effects of ocotillol on its cardiotoxicity remain unclear. In the current study, the effects of ocotillol on the toxicity of Dox were investigated, particularly its role in cardiotoxicity. In the acute injury model, pre-administration of ocotillol prolonged the survival time. In the chronic animal model, pre-administration of ocotillol decreased the elevated levels of plasma creatine kinase (CK) and CK-MB, as well as attenuated the pathological changes that occurred. Pre-treatment with ocotillol ameliorated the decreased glutathione level and reduced the cumulated malondialdehyde in the heart tissue. In addition, pre-treatment with ocotillol restored the lowered white blood cell count. The results indicate that Dox co treatment with ocotillol may effectively alleviate its associated toxic injury, particularly cardiotoxicity. Thus, co-administration of Dox with ocotillol may be a potential therapeutic strategy. PMID- 24220652 TI - Endoreduplication is not involved in bundle-sheath formation in the C4 species Cleome gynandra. AB - There is currently significant interest in engineering the two-celled C4 photosynthesis pathway into crops such as rice in order to increase yield. This will require alterations to the biochemistry of photosynthesis in both mesophyll (M) and bundle-sheath (BS) cells, but also alterations to leaf anatomy. For example, the BS of C4 species is enlarged compared with that in C3 species. Because cell and nucleus size are often correlated, this study investigated whether nuclear endoreduplication is associated with increased differentiation and expansion of BS cells. Nuclei in the BS of C4 Cleome gynandra were tagged with green fluorescent protein. Confocal laser-scanning microscopy and flow cytometry of isolated nuclei were used to quantify size and DNA content in BS cells. The results showed a significant endoreduplication in BS cells of C. gynandra but not in additional C4 lineages from both the monocotyledonous and dicotyledenous plants. Furthermore, in the C3 species Arabidopsis thaliana, BS cells undergo endoreduplication. Due to this significant endoreduplication in the small BS cells of C3 A. thaliana, it was concluded that endoreduplication of BS nuclei in C4 plants is not linked to expansion and differentiation of BS cells, and therefore that alternative strategies to increase this compartment need to be sought in order to engineer C4 traits into C3 crops such as rice. PMID- 24220654 TI - Calcium partitioning and allocation and blossom-end rot development in tomato plants in response to whole-plant and fruit-specific abscisic acid treatments. AB - The mechanisms regulating Ca(2+) partitioning and allocation in plants and fruit remain poorly understood. The objectives of this study were to determine Ca(2+) partitioning and allocation in tomato plants and fruit in response to whole-plant and fruit-specific abscisic acid (ABA) treatments, as well as to analyse the effect of changes in Ca(2+) partitioning and allocation on fruit susceptibility to the Ca(2+) deficiency disorder blossom-end rot (BER) under water stress conditions. Tomato plants of the cultivar Ace 55 (Vf) were grown in a greenhouse and exposed to low Ca(2+) conditions during fruit growth and development. Starting 1 day after pollination (DAP), the following treatments were initiated: (i) whole plants were sprayed weekly with deionized water (control) or (ii) with 500mg l(-1) ABA; or fruit on each plant were dipped weekly (iii) in deionized water (control) or (iv) in 500mg l(-1) ABA. At 15 DAP, BER was completely prevented by whole-plant or fruit-specific ABA treatments, whereas plants or fruit treated with water had 16-19% BER incidence. At 30 DAP, BER was prevented by the whole-plant ABA treatment, whereas fruit dipped in ABA had a 16% and water treated plants or fruit had a 36-40% incidence of BER. The results showed that spraying the whole plant with ABA increases xylem sap flow and Ca(2+) movement into the fruit, resulting in higher fruit tissue and water-soluble apoplastic Ca(2+) concentrations that prevent BER development. Although fruit-specific ABA treatment had no effect on xylem sap flow rates or Ca(2+) movement into the fruit, it increased fruit tissue water-soluble apoplastic Ca(2+) concentrations and reduced fruit susceptibility to BER to a lesser extent. PMID- 24220653 TI - NO homeostasis is a key regulator of early nitrate perception and root elongation in maize. AB - Crop plant development is strongly dependent on nitrogen availability in the soil and on the efficiency of its recruitment by roots. For this reason, the understanding of the molecular events underlying root adaptation to nitrogen fluctuations is a primary goal to develop biotechnological tools for sustainable agriculture. However, knowledge about molecular responses to nitrogen availability is derived mainly from the study of model species. Nitric oxide (NO) has been recently proposed to be implicated in plant responses to environmental stresses, but its exact role in the response of plants to nutritional stress is still under evaluation. In this work, the role of NO production by maize roots after nitrate perception was investigated by focusing on the regulation of transcription of genes involved in NO homeostasis and by measuring NO production in roots. Moreover, its involvement in the root growth response to nitrate was also investigated. The results provide evidence that NO is produced by nitrate reductase as an early response to nitrate supply and that the coordinated induction of non-symbiotic haemoglobins (nsHbs) could finely regulate the NO steady state. This mechanism seems to be implicated on the modulation of the root elongation in response to nitrate perception. Moreover, an improved agar-plate system for growing maize seedlings was developed. This system, which allows localized treatments to be performed on specific root portions, gave the opportunity to discern between localized and systemic effects of nitrate supply to roots. PMID- 24220655 TI - Impacts of predicted climate change on recruitment at the geographical limits of Scots pine. AB - Ongoing changes in global climate are having a significant impact on the distribution of plant species, with effects particularly evident at range limits. We assessed the capacity of Pinus sylvestris L. populations at northernmost and southernmost limits of the distribution to cope with projected changes in climate. We investigated responses including seed germination and early seedling growth and survival, using seeds from northernmost (Kevo, Finland) and southernmost (Granada, Spain) populations. Seeds were grown under current climate conditions in each area and under temperatures increased by 5 degrees C, with changes in precipitation of +30% or -30% with reference to current values at northern and southern limits, respectively, in a fully factorial controlled conditions experimental design. Increased temperatures reduced germination time and enhanced biomass gain at both range edges but reduced survival at the southern range edge. Higher precipitation also increased survival and biomass but only under a southern climate. Seeds from the southern origin emerged faster, produced bigger seedlings, allocated higher biomass to roots, and survived better than northern ones. These results indicate that recruitment will be reduced at the southernmost range of the species, whereas it will be enhanced at the northern limit, and that the southern seed sources are better adapted to survive under drier conditions. However, future climate will impose a trade-off between seedling growth and survival probabilities. At the southern range edge, higher growth may render individuals more susceptible to mortality where greater aboveground biomass results in greater water loss through evapotranspiration. PMID- 24220656 TI - Light perception and signalling by phytochrome A. AB - In etiolated seedlings, phytochrome A (phyA) mediates very-low-fluence responses (VLFRs), which initiate de-etiolation at the interphase between the soil and above-ground environments, and high-irradiance responses (HIR), which complete de etiolation under dense canopies and require more sustained activation with far red light. Light-activated phyA is transported to the nucleus by FAR-RED ELONGATED HYPOCOTYL1 (FHY1). The nuclear pool of active phyA increases under prolonged far-red light of relatively high fluence rates. This condition maximizes the rate of FHY1-phyA complex assembly and disassembly, allowing FHY1 to return to the cytoplasm to translocate further phyA to the nucleus, to replace phyA degraded in the proteasome. The core signalling pathways downstream of nuclear phyA involve the negative regulation of CONSTITUTIVE PHOTOMORPHOGENIC 1, which targets for degradation transcription factors required for photomorphogenesis, and PHYTOCHROME-INTERACTING FACTORs, which are transcription factors that repress photomorphogenesis. Under sustained far-red light activation, released FHY1 can also be recruited with active phyA to target gene promoters as a transcriptional activator, and nuclear phyA signalling activates a positive regulatory loop involving BELL-LIKE HOMEODOMAIN 1 that reinforces the HIR. PMID- 24220658 TI - Polymyxin B agonist capture therapy for intrauterine inflammation: proof-of principle in a fetal ovine model. AB - Intrauterine infection is a leading cause of preterm birth (PTB), most notably in deliveries occurring before 32 weeks gestation. Preterm infants exposed to intrauterine inflammation are more likely to have a host of neurological, respiratory, gastrointestinal, and visual pathologies. Preventing preterm delivery and protecting the fetus from injury is thus likely to require treatment of both intrauterine infection and inflammation. Polymyxin B (PMXB) is a cationic peptide antibiotic that binds Escherichia coli lipopolysaccharides (LPS) and prevents inflammatory activation. We hypothesized that intraamniotic administration of PMXB would selectively inhibit LPS-driven inflammation, serving as a proof-of-principle for targeted agonist capture therapy as a treatment for PTB and fetal injury. In vitro studies with primary fetal ovine keratinocytes demonstrated a significant and sustained reduction in tumor necrosis factor alpha and interleukin 8 messenger RNA expression after treatment with PMXB and LPS, relative to cells treated with LPS alone. In vivo studies with fetal sheep demonstrated a significant reduction in proinflammatory cytokines in the amniotic fluid and fetal lung (but not fetal skin or chorioamnion) in LPS + PMXB-treated animals, relative to those treated with LPS alone. These data are consistent with a partial resolution of LPS-driven intrauterine inflammation. They suggest the potential for agonist capture as a conceptual means of resolving the proparturition inflammation caused by infection of the amniotic cavity. PMID- 24220657 TI - The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis. AB - NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PMID- 24220659 TI - An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis. AB - Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An 'aggregation-prone' heptapeptide ((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptide self assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF). PMID- 24220661 TI - Zerumbone inhibits tumor angiogenesis via NF-kappaB in gastric cancer. AB - Zerumbone derived from a subtropical ginger, Zingiber zerumbet Smith, was previously reported to have antitumor growth and anti-inflammatory properties in some types of cancer. However, the effects of zerumbone against cancer angiogenesis have not been fully elucidated. In this study, we clarified the role of zerumbone in gastric cancer angiogenesis. We examined the expression of vascular endothelial growth factor (VEGF) in gastric cancer cell lines both in the basal state and following zerumbone treatment by real-time RT-PCR and enzyme linked immunosorbent assay (ELISA). Changes in gastric cancer cell proliferation in response to zerumbone treatment were measured by WST-1 assay. Additionally, the effects of zerumbone on NF-kappaB activity were examined in AGS cells. Finally, the effects of zerumbone on angiogenesis in AGS cells were measured by in vitro angiogenesis assay in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were cocultured with AGS cells. Among the 6 gastric cancer cell lines tested, AGS cells exhibited the highest expression of VEGF. Cell proliferation, VEGF expression and NF-kappaB activity in AGS cells were all significantly inhibited by zerumbone. Moreover, the tube formation area of HUVECs was increased by coculture with AGS cells, and this effect was inhibited by zerumbone. Both VEGF expression and NF-kappaB activity in AGS cells were reduced by treatment with zerumbone, thereby inhibiting angiogenesis. Thus, zerumbone may become a new anti-angiogenic and antitumor drug in the treatment of gastric cancer. PMID- 24220660 TI - A KT intervention including the evidence alert system to improve clinician's evidence-based practice behavior--a cluster randomized controlled trial. AB - BACKGROUND: It is difficult to foster research utilization among allied health professionals (AHPs). Tailored, multifaceted knowledge translation (KT) strategies are now recommended but are resource intensive to implement. Employers need effective KT solutions but little is known about; the impact and viability of multifaceted KT strategies using an online KT tool, their effectiveness with AHPs and their effect on evidence-based practice (EBP) decision-making behavior. The study aim was to measure the effectiveness of a multifaceted KT intervention including a customized KT tool, to change EBP behavior, knowledge, and attitudes of AHPs. METHODS: This is an evaluator-blinded, cluster randomized controlled trial conducted in an Australian community-based cerebral palsy service. 135 AHPs (physiotherapists, occupational therapists, speech pathologists, psychologists and social workers) from four regions were cluster randomized (n = 4), to either the KT intervention group (n = 73 AHPs) or the control group (n = 62 AHPs), using computer-generated random numbers, concealed in opaque envelopes, by an independent officer. The KT intervention included three-day skills training workshop and multifaceted workplace supports to redress barriers (paid EBP time, mentoring, system changes and access to an online research synthesis tool). Primary outcome (self- and peer-rated EBP behavior) was measured using the Goal Attainment Scale (individual level). Secondary outcomes (knowledge and attitudes) were measured using exams and the Evidence Based Practice Attitude Scale. RESULTS: The intervention group's primary outcome scores improved relative to the control group, however when clustering was taken into account, the findings were non-significant: self-rated EBP behavior [effect size 4.97 (95% CI -10.47, 20.41) (p = 0.52)]; peer-rated EBP behavior [effect size 5.86 (95% CI -17.77, 29.50) (p = 0.62)]. Statistically significant improvements in EBP knowledge were detected [effect size 2.97 (95% CI 1.97, 3.97 (p < 0.0001)]. Change in EBP attitudes was not statistically significant. CONCLUSIONS: Improvement in EBP behavior was not statistically significant after adjusting for cluster effect, however similar improvements from peer-ratings suggest behaviorally meaningful gains. The large variability in behavior observed between clusters suggests barrier assessments and subsequent KT interventions may need to target subgroups within an organization. TRIAL REGISTRATION: Registered on the Australian New Zealand Clinical Trials Registry (ACTRN12611000529943). PMID- 24220662 TI - Comparative evaluation of two different volumes of lidocaine in intravenous regional anesthesia. AB - BACKGROUND: This study was conducted to compare low concentration-high volume intravenous regional anesthesia (IVRA) method with local anesthetic method in upper extremity surgery in terms of efficiency and adverse effects. MATERIAL AND METHODS: Thirty-nine patients were divided into 2 groups; the first group received a 2% concentration of 12-15 mL lidocaine (Group 1) and the second group received a 0.5% concentration of 30-50 mL lidocaine (Group 2). Intraoperative hemodynamic data of patients (systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and peripheral oxygen saturation- SpO2) was recorded before and after anesthesia at 1, 5, 10, 15, 20, and 40 minutes. RESULTS: The intergroup and intragroup comparisons did not reveal any significant differences in hemodynamic data. The onset time of sensorial block was shorter and the regression time of sensorial block was longer in Group 1 than Group 2. Group 1 had shorter onset time of motor block and longer regression time of motor block than Group 2. There were no significant differences between the study groups in terms of the time of tourniquet and postoperative analgesia time. CONCLUSIONS: IVRA technique applied with 2% concentration and volume of 12-15 mL lidocaine may be suggested as a safe option. PMID- 24220663 TI - Impact of phytopathogen infection and extreme weather stress on internalization of Salmonella Typhimurium in lettuce. AB - Internalization of human pathogens, common in many types of fresh produce, is a threat to human health since the internalized pathogens cannot be fully inactivated/removed by washing with water or sanitizers. Given that pathogen internalization can be affected by many environmental factors, this study was conducted to investigate the influence of two types of plant stress on the internalization of Salmonella Typhimurium in iceberg lettuce during pre-harvest. The stresses were: abiotic (water stress induced by extreme weather events) and biotic (phytopathogen infection by lettuce mosaic virus [LMV]). Lettuce with and without LMV infection were purposefully contaminated with green fluorescence protein-labeled S. Typhimurium on the leaf surfaces. Lettuce was also subjected to water stress conditions (drought and storm) which were simulated by irrigating with different amounts of water. The internalized S. Typhimurium in the different parts of the lettuce were quantified by plate count and real-time quantitative PCR and confirmed with a laser scanning confocal microscope. Salmonella internalization occurred under the conditions outlined above; however internalization levels were not significantly affected by water stress alone. In contrast, the extent of culturable S. Typhimurium internalized in the leafy part of the lettuce decreased when infected with LMV under water stress conditions and contaminated with high levels of S. Typhimurium. On the other hand, LMV-infected lettuce showed a significant increase in the levels of culturable bacteria in the roots. In conclusion, internalization was observed under all experimental conditions when the lettuce surface was contaminated with S. Typhimurium. However, the extent of internalization was only affected by water stress when lettuce was infected with LMV. PMID- 24220664 TI - Genetic environment of the multi-resistance gene cfr in methicillin-resistant coagulase-negative staphylococci from chickens, ducks, and pigs in China. AB - The present study focussed on the analysis of the genetic environment of the multi-resistance gene cfr detected among 21, mostly methicillin-resistant, coagulase-negative Staphylococcus (CoNS) isolates obtained from chickens, ducks and pigs in China. It included sequencing of the regions up- and downstream of the cfr gene on various plasmid types in 13 isolates, such as pSS-02 and pSS-02 like (n=7), pSS-03-like (n=1), pJP1-like (n=3), pSS-04 (n=1) and pJP2 (n=1). This analysis revealed that insertion sequences (IS21-558, IS256, IS257, or IS1216E) and other resistance genes (aacA-aphD and aadD for aminoglycoside resistance, ble for bleomycin resistance, fosD for fosfomycin resistance, erm(B) and erm(C) for macrolide-lincosamide-streptogramin B resistance, or fexA for phenicol resistance) coexisted on the respective plasmids. In the chromosomal copies of cfr identified in eight S. lentus isolates, the cfr gene was found to be bracketed by insertion sequences, such as IS256 or ISEnfa5. Stability tests confirmed that all chromosomal cfr-containing regions could be looped out via IS mediated recombination. The observations made in this study extend the rather rudimentary knowledge about the genetic environment of cfr in staphylococci from chickens and ducks and confirmed that insertion sequences play an important role in the dissemination of cfr, not only among different types of plasmids, but also for the integration in the chromosomal DNA. PMID- 24220665 TI - Viridans and bovis group streptococci that cause infective endocarditis in two regions with contrasting epidemiology. AB - Viridans group (VGS) or bovis group streptococci (BGS) are the major causes for streptococcal infective endocarditis (IE). However, the causative isolates are not sufficiently characterized. Using multilocus sequence analysis we have examined VGS and BGS (VGS/BGS) isolates that caused IE in southern India and Germany, two distant geographic regions with a contrasting IE epidemiology. Other than in Germany, the majority of patients (68%) in Chennai, southern India had an underlying rheumatic heart disease (RHD). In accord with the high prevalence of RHD in the younger population and with the expansive age structure of India, the median age (24 years) of the VGS/BGS endocarditis patients was lower than in Germany (63 years), where RHD is rare and the age structure is contractive. Both in Germany and in southern India, the majority of cases were caused by mitis group streptococci, however, with considerable differences in the spectra of causative (sub)species. BGS endocarditis was more frequent in Germany. The spectrum of VGS/BGS that cause IE differs considerably between distant geographic regions in which different predisposing conditions prevail. Therefore, improved microbiological diagnosis in IE may facilitate determination of the optimal therapy. PMID- 24220666 TI - Indications and outcomes for 100 patients managed with a pectoralis major flap within a UK maxillofacial unit. AB - There are few studies reporting the role of the pedicled pectoralis major (PPM) flap in modern maxillofacial practice. The outcomes of 100 patients (102 flaps) managed between 1996 and 2012 in a UK maxillofacial unit that preferentially practices free tissue reconstruction are reported. The majority (88.2%) of PPM flaps were for oral squamous cell carcinoma (SCC), stage IV (75.6%) disease, and there was substantial co-morbidity (47.0% American Society of Anesthesiologists 3 or 4). The PPM flap was the preferred reconstruction on 80.4% of occasions; 19.6% followed free flap failure. Over half of the patients (57%) had previously undergone major surgery and/or chemoradiotherapy. Ischaemic heart disease (P=0.028), diabetes mellitus (P=0.040), and methicillin-resistant Staphylococcus aureus (MRSA) infection (P=0.013) were independently associated with flap loss (any degree). Free flap failure was independently associated with total (2.0%) and major (6.9%) partial flap loss (P=0.044). Cancer-specific 5-year survival for stage IV primary SCC and salvage surgery improved in the second half (2005-2012) of the study period (22.2% vs. 79.8%, P=0.002, and 0% vs. 55.7%, P=0.064, respectively). There were also declines in recurrent disease (P=0.008), MRSA (P<0.001), and duration of admission (P=0.014). The PPM flap retains a valuable role in the management of advanced disease combined with substantial co morbidity, and following free flap failure. PMID- 24220667 TI - Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive-compulsive disorder. AB - OBJECTIVE: Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. METHOD: A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. RESULTS: Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). CONCLUSIONS: These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction. PMID- 24220668 TI - 1-Pentamethylbenzyl-3-(n)buthylbenzimidazolesilver(I)bromide complex: synthesis, characterization and DFT calculations. AB - A novel NHC complex of silver(I) ion, 1-pentamethylbenzyl-3 (n)buthylbenzimidazolesilver(I)bromide, was prepared and fully characterized by single crystal X-ray structure determination. FT-IR, NMR and UV-vis spectroscopies were employed to investigate the electronic transition behaviors of the complex. Additionally, the molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift and electronic transition values of silver(I) complex were calculated by using density functional theory levels (B3LYP and PBE1PBE) with LANL2DZ basis set. Also, the vibrational frequencies were supported on the basis of the potential energy distribution (PED) analysis calculated for PBE1PBE level. We were also investigated total static dipole moment (MU), the mean polarizability (), the anisotropy of the polarizability (Deltaalpha), the mean first-order hyperpolarizability () of the title complex. Natural bond orbital (NBO) analysis was performed to determine the presence of hyperconjugative interactions, and charge distributions. PMID- 24220669 TI - MgO:Eu3+ red nanophosphor: low temperature synthesis and photoluminescence properties. AB - Nanoparticles of Eu(3+) doped (0-9 mol%) MgO were prepared using low temperature (400 degrees C) solution combustion technique with metal nitrate as precursor and glycine as fuel. The powder X-ray diffraction (PXRD) patterns of the as-formed products show single cubic phase and no further calcination was required. The crystallite size was obtained using Scherer's formula and was found to be 5-6 nm. The effect of Eu(3+) ions on luminescence characteristics of MgO was studied and the results were discussed in detail. These phosphors exhibit bright red emission upon 395 nm excitation. The characteristic photoluminescence (PL) emission peaks at ~580, 596, 616, 653, 696 and 706 nm ((5)D0->(7)Fj=0, 1, 2, 3, 4) were recorded due to Eu(3+) ions. The electronic transition corresponding to (5)D0->(7)F2 of Eu(3+) ions (616 nm) was stronger than the magnetic dipole transition corresponding to (5)D0->(7)F1 of Eu(3+) ions (596 nm). The international commission on illumination (CIE) chromaticity co-ordinates were calculated from emission spectra, the values (x, y) were very close to national television system committee (NTSC) standard value of red emission. Therefore the present phosphor was highly useful for display applications. PMID- 24220670 TI - Experimental and theoretical studies of 2,5-dichloroanilinium picrate. AB - Organic 2,5-dichloroanilinium picrate crystal was grown by using slow evaporation solution technique. The lattice parameter was estimated by powder X-ray diffraction. The absence of absorption at around Nd:YAG fundamental wavelength was confirmed by ultraviolet-visible absorption study. The vibrational analyses confirm the various functional groups present in the grown crystal. The NMR study confirms the presence of chemical environment of hydrogen in the title crystal. The thermogravimetric (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) traces reveals the thermal stability of the compound. The second harmonic generation (SHG) of the crystal was confirmed by Kurtz Perry powder technique. The theoretical studies such as first-order hyperpolarizability (beta), molecular orbitals, electronic excitation and electrostatic potential (ESP) were performed using Gaussian 03W software at HF/6-31G (d) level. PMID- 24220671 TI - Synthesis of silver nanocubes as a SERS substrate for the determination of pesticide paraoxon and thiram. AB - The silver cube-like nanostructure with uniform size and high yield have been synthesized through the rapid sulfide-mediated polyol method. The morphology, structure and optical properties of the as-prepared silver nanocubes were characterized by UV-Visible spectroscopy, field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD). The Surface-Enhanced Raman Scattering (SERS) performance of the as-prepared Ag nanocubes was characterized by crystal violet (CV) as the probe molecules. Furthermore, the low levels of thiram and pesticide paraoxon can be detected by the SERS technique, which shows that the silver nanocubes as a SERS substrate have excellent sensitivity and reproducibility. PMID- 24220672 TI - Synthesis, interaction with DNA and antiproliferative activities of two novel Cu(II) complexes with Schiff base of benzimidazole. AB - Two novel copper(II) complexes with Schiff base of benzimidazole [Cu(L)Cl]2.CH3OH have been synthesized. HL(1) (N-(benzimidazol-2-ymethyl)-5 chlorosalicylideneimine, C15H11ClN3O) and HL(2) (N-(benzimidazol-2-ymethyl) salicylideneimine, C15H12N3O) are ligands of complex (1) and complex (2), respectively. The complexes were characterized by elemental analysis, IR, UV-Vis, TGA and X-ray diffraction. Within the complexes, Cu(II) ions were four coordinated by two nitrogen atom of azomethine and imine, one phenolic oxygen atom from HL and one chloride atom. A distorted quadrilateral structure was formed. Complex (1) crystallized in the triclinic crystal system. Results showed that pi-pi stacking effect occurred due to the existence of aromatic ring from Schiff base and hydrogen bonding between methanol and adjacent atoms. The DNA binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra and viscosity measurements. Results indicated that complexes bound to DNA via partial intercalation mode. The DNA binding constants Kb/(L mol(-1)) were 1.81*10(4) (1), 1.37*10(4) (2), 6.27*10(3) (HL(1)) and 3.14*10(3) (HL(2)) at 298 K. The title complexes could quench the emission intensities of EB-DNA system significantly. The results of agarose gel electrophoresis indicated complex (1) could cleave supercoiled DNA through the oxidative mechanism. The inhibition ratios revealed that complex (1) and HL(1) had strong antiproliferative activities against human breast cancer cells (MCF-7) lines and human colorectal cancer cells (COLO205) lines in vitro. The antiproliferative activities of complex (1) against MCF-7 lines (IC50=16.9+/-1.5 MUmol L(-1)) and against COLO205 lines (IC50=16.5+/-3.4 MUmol L(-1)) is much stronger than that of HL(1), which had the potential to develop anti-cancer drug. PMID- 24220674 TI - Coronary endothelial function in patients with obstructive sleep apnea. AB - OBJECTIVE: Obstructive sleep apnea (OSA) has been associated with increased risk for cardiovascular events, possibly mediated by endothelial dysfunction. The current study evaluates the association between invasive coronary endothelial dysfunction and OSA in patients with nonobstructive coronary atherosclerosis. METHODS: All patients who had undergone both polysomnography and an invasive coronary vasomotor study at the Mayo Clinic, Rochester, Minnesota, from January 1997 to August 2011 were identified (n=143). OSA was defined as an apnea-hypopnea index of 5 or higher. Three endpoints of coronary endothelial function - percentage change in coronary artery diameter at the mid and distal left anterior descending artery to intracoronary acetylcholine and percentage change in coronary blood flow to intracoronary acetylcholine - were assessed. Differences between patients with OSA (n=102) and those without OSA (n=41) were evaluated using multivariate analysis of variance. Follow-up mortality data were collected and Kaplan-Meier curves were plotted to evaluate differences in mortality between patients with and without OSA. RESULTS: Patients with OSA were more likely to have hypertension compared with patients without OSA. OSA was not significantly associated with coronary endothelial dysfunction on univariate analysis (P=0.23) and after adjustment for hypertension (P=0.19). Similarly, there was no significant difference in coronary endothelial function in patients who had oxygen desaturation of less than 90% during polysomnography (P=0.42). There was a trend toward higher mortality in patients with OSA compared with those without OSA, but this did not reach statistical significance (5 vs. 0% at 10 years, P=0.25). CONCLUSION: The current study suggests that OSA is not an independent risk factor for coronary endothelial dysfunction in patients with early coronary atherosclerosis. Adverse coronary outcomes in patients with OSA may be independent of coronary endothelial dysfunction. PMID- 24220673 TI - Genetics and epigenetics of adrenocortical tumors. AB - Adrenocortical tumors are common neoplasms. Most are benign, nonfunctional and clinically irrelevant. However, adrenocortical carcinoma is a rare disease with a dismal prognosis and no effective treatment apart from surgical resection. The molecular genetics of adrenocortical tumors remain poorly understood. For decades, molecular studies relied on a small number of samples and were directed to candidate-genes. This approach, based on the elucidation of the genetics of rare genetic syndromes in which adrenocortical tumors are a manifestation, has led to the discovery of major dysfunctional molecular pathways in adrenocortical tumors, such as the IGF pathway, the Wnt pathway and TP53. However, with the advent of high-throughput methodologies and the organization of international consortiums to obtain a larger number of samples and high-quality clinical data, this paradigm is rapidly changing. In the last decade, genome-wide expression profile studies, microRNA profiling and methylation profiling allowed the identification of subgroups of tumors with distinct genetic markers, molecular pathways activation patterns and clinical behavior. As a consequence, molecular classification of tumors has proven to be superior to traditional histological and clinical methods in prognosis prediction. In addition, this knowledge has also allowed the proposal of molecular-targeted approaches to provide better treatment options for advanced disease. This review aims to summarize the most relevant data on the rapidly evolving field of genetics of adrenal disorders. PMID- 24220676 TI - A comparison of cell salvage strategies in posterior spinal fusion for adolescent idiopathic scoliosis. AB - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare the efficacy of 3 blood management strategies in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) in reducing donor blood transfusion. SUMMARY OF BACKGROUND DATA: Although intraoperative cell salvage and predonated banked blood may be effective in reducing donor blood transfusion in the perioperative period, the optimal blood management strategy is unclear. A combined cell salvage strategy holds several potential advantages but has not yet been investigated. METHODS: Patients who underwent isolated PSF for AIS (n=167) were subdivided into 3 groups by perioperative blood management strategy: (1) intraoperative retransfusion of shed blood (cell saver) and predonated autologous banked blood (n=51); (2) cell saver alone (n=33); and (3) combined cell saver and postoperative collection and retransfusion of drained blood (Retransfusion drain) (n=83). Data collected included age, sex, diagnosis, body weight, number of levels fused, operative time, intraoperative and postoperative blood loss and retransfusion, preoperative and postoperative (72 h) hemoglobin and hematocrit (Hct), and amount of autologous and donor blood transfused in the perioperative period. RESULTS: Fewer patients in the cell saver and predonated blood (3.9%) and cell saver and retransfusion drain (1.2%) groups received donor transfusions than did those managed with cell saver alone (33%). There was no significant difference in the donor transfusion rate between cell saver/predonated blood and retransfusion groups. Mean postoperative Hct (72 h) was higher in the retransfusion group 3 than in the other 2 (group 3: 29.3%, group 1: 25.4%, group 2: 26.1%). There was no significant difference in the mean change in hemoglobin and Hct after surgery between the 3 groups. CONCLUSIONS: The present study demonstrates the efficacy of a combined intraoperative and postoperative cell salvage strategy in PSF for AIS, significantly reducing perioperative donor blood transfusions, maintaining physiological Hct, and conserving blood bank resources. PMID- 24220675 TI - A differential dielectric affinity glucose sensor. AB - A continuous glucose monitor with a differential dielectric sensor implanted within the subcutaneous tissue that determines the glucose concentration in the interstitial fluid is presented. The device, created using microelectromechanical systems (MEMS) technology, consists of sensing and reference modules that are identical in design and placed in close proximity. Each module contains a microchamber housing a pair of capacitive electrodes residing on the device substrate and embedded in a suspended, perforated polymer diaphragm. The microchambers, enclosed in semi-permeable membranes, are filled with either a polymer solution that has specific affinity to glucose or a glucose-insensitive reference solution. To accurately determine the glucose concentration, changes in the permittivity of the sensing and the reference solutions induced by changes in glucose concentration are measured differentially. In vitro characterization demonstrated the sensor was capable of measuring glucose concentrations from 0 to 500 mg dL(-1) with resolution and accuracy of ~1.7 MUg dL(-1) and ~1.74 mg dL( 1), respectively. In addition, device drift was reduced to 1.4% (uncontrolled environment) and 11% (5 degrees C of temperature variation) of that from non differential measurements, indicating significant stability improvements. Preliminary animal testing demonstrated that the differential sensor accurately tracks glucose concentration in blood. This sensor can potentially be used clinically as a subcutaneously implanted continuous monitoring device in diabetic patients. PMID- 24220677 TI - alpha-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush. AB - AIMS: Activation of retinal microglial cells (RMCs) is known to contribute to retinal ganglion cell (RGC) death after optic nerve injury. The purpose of this study was to investigate the effects of intravenous injection of alpha-crystallin on RGC survival and RMC activation in a rat model of optic nerve crush. MAIN METHODS: RGCs were retrogradely labeled with fluorogold. Rats were intravenously injected with normal saline or alpha-crystallin (0.05g/kg, 0.5g/kg, and 5 g/kg) at 2, 4, 6, 8, 10, and 12 days after the optic nerve crush. Activated RMCs were characterized using immunofluorescence labeling with CD11b, and TNF-alpha and iNOS expression was detected using immunoblot analyses. We analyzed the morphology and numbers of RGC and RMC 2 and 4 weeks after injury using fluorescence and confocal microscopy. KEY FINDINGS: The number of RGCs decreased after optic nerve injury, accompanied by significantly increased numbers of activated RMCs. Intravenous injection of alpha-crystallin decreased the number of RMCs, and enhanced the number of RGCs compared to saline injection. alpha Crystallin administration inhibited TNF-alpha and iNOS protein expression induced by optic nerve injury. SIGNIFICANCE: Our results suggest that alpha-crystallin promotes RGC survival and inhibits RMC activation. Intravenous injection of alpha crystallin could be a possible strategy for the treatment of optic nerve injury. PMID- 24220678 TI - Blockage of TRPM7 channel induces hepatic stellate cell death through endoplasmic reticulum stress-mediated apoptosis. AB - AIMS: Proliferation is a 'multiplier' for extracellular matrix production and contraction of activated hepatic stellate cells (HSC) in fibrotic liver. Transient receptor potential melastatin-like 7 channels (TRPM7) are implicated in the survival and proliferation of several kinds of cells. This study was aimed to investigate the effect of TRPM7 blocker 2-APB on survival and proliferation of HSC and the underlying mechanisms. MAIN METHODS: Rat HSC were stimulated by 2-APB for 24 h and then collected for further use. Cell viability was detected by MTT, and apoptosis was determined by AnnexinV/PI staining and TUNEL assay. Gene expressions of TRPM7, alpha-SMA, bcl-2, bax, and endoplasmic reticulum (ER) stress key members CHOP, caspase-12, ATF4, ATF6, Xbp1, GRP78 and calnexin were evaluated with quantitative RT-PCR. Quantifications of alpha-SMA, TRPM7, CHOP and GRP78 proteins were carried out by Western blot. Transmission electron microscopy and Xbp1 mRNA splicing analysis were also used for detection of ER stress. KEY FINDINGS: 2-APB decreased TRPM7 and alpha-SMA expressions in primary HSC, and inhibited proliferation of activated HSC in a dose-dependent manner. 2-APB also decreased total count of activated HSC and increased the number of apoptotic cells. 2-APB increased expressions of bax and ER stress key factors CHOP, caspase 12, ATF4, ATF6, Xbp1, GRP78 and calnexin. Meanwhile, ultra-structural ER changes and spliced Xbp1 mRNA were also observed in 2-APB treated HSC. SIGNIFICANCE: Blockage of TRPM7 could inhibit activation and proliferation of primary HSC and induce apoptotic death of activated cells, in which ER stress was identified as one of possible underlying molecular bases. PMID- 24220679 TI - Heat-shock protein dysregulation is associated with functional and pathological TDP-43 aggregation. AB - Conformational disorders are involved in various neurodegenerative diseases. Reactive oxygen species (ROS) are the major contributors to neurodegenerative disease; however, ROS that affect the structural changes in misfolded disease proteins have yet to be well characterized. Here we demonstrate that the intrinsic propensity of TDP-43 to aggregate drives the assembly of TDP-43 positive stress granules and soluble toxic TDP-43 oligomers in response to a ROS insult via a disulfide crosslinking-independent mechanism. Notably, ROS-induced TDP-43 protein assembly correlates with the dynamics of certain TDP-43-associated chaperones. The heat-shock protein (HSP)-90 inhibitor 17-AAG prevents ROS-induced TDP-43 aggregation, alters the type of TDP-43 multimers and reduces the severity of pathological TDP-43 inclusions. In summary, our study suggests that a common mechanism could be involved in the pathogenesis of conformational diseases that result from HSP dysregulation. PMID- 24220681 TI - Protection of mesenchymal stem cells on acute kidney injury. AB - The aim of the present study was to determine the protection of allogeneic bone marrow mesenchymal stem cells (BMSCs) on an ischaemia/reperfusion (I/R)-induced acute kidney injury (AKI) rat model and to investigate the underlying mechanisms. The BMSCs were isolated and cultured from adult Sprague-Dawley (SD) rats and the I/R-induced AKI model was established by bilateral clamping of renal pedicles for 60 min. Following successfully establishing the AKI model, 1x106 BMSCs were administered by intrarenal injection. All animals were randomly divided into four groups (n=10 in each): 1 (sham control), 2 (I/R), 3 (I/R+culture medium) and 4 (I/R+BMSCs). Serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured in all four groups at 24 and 72 h. Three days post-surgery, the level of inflammatory factors, including interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the kidney was analysed by quantitative polymerase chain reaction. Three days following surgery, mRNA expression levels of IL-6 and TNF-alpha were significantly lower, however, the expression level of VEGF was significantly higher in group 4 compared with groups 2 and 3 (P<0.05). By contrast, the immunofluorescence results showed that the injected BMSCs differentiated into vascular endothelial cells. In conclusion, the present study identified that intrarenal administration of BMSCs improved I/R induced AKI through the anti-inflammatory effect and a paracrine mechanism and therefore, may be hypothesised for the use in clinical trials. PMID- 24220682 TI - How much do preexisting chronic conditions contribute to age differences in health care expenditures after a work-related musculoskeletal injury? AB - OBJECTIVES: To estimate the contribution of preexisting chronic conditions on age differences in health care expenditures for the management of work-related musculoskeletal injuries in British Columbia. METHODS: A secondary analysis of workers' compensation claims submitted over the 5-year period between January 1, 2002 and December 31, 2006 (N = 55,827 claims among men and 32,141 claims among women). Path models examined the relationships between age and health care expenditures, and the extent to which age differences in health care expenditures were mediated by preexisting chronic conditions. Models were adjusted for individual, injury, occupational, and industrial covariates. RESULTS: The relationship between age and health care expenditures differed for men and women, with a stronger age gradient observed among men. Preexisting osteoarthritis and coronary heart disease were associated with elevated health care expenditures among men and women. Diabetes was associated with elevated health care expenditures among men only, and depression was associated with elevated health care expenditures among women only. The percentage of the age effect on health care expenditures that was mediated through preexisting chronic conditions increased from 12.4% among 25-34-year-old men (compared with 15-24 y) to 26.6% among 55+-year-old men; and 14.6% among 25-34-year-old women to 35.9% among women 55 and older. CONCLUSIONS: The results of this study demonstrate that differences in preexisting chronic conditions have an impact on the relationship between older age and greater health care expenditures after a work-related musculoskeletal injury. The differing prevalence of preexisting osteoarthritis, coronary heart disease, and to a lesser extent diabetes (among men) and depression (among women) across age groups explain a nontrivial proportion of the age effect in health care expenditures after injury. However, approximately two thirds or more of the age effect in health care expenditures remains unexplained. PMID- 24220680 TI - Sensitivity to Flg22 is modulated by ligand-induced degradation and de novo synthesis of the endogenous flagellin-receptor FLAGELLIN-SENSING2. AB - FLAGELLIN-SENSING2 (FLS2) is the plant cell surface receptor that perceives bacterial flagellin or flg22 peptide, initiates flg22-signaling responses, and contributes to bacterial growth restriction. Flg22 elicitation also leads to ligand-induced endocytosis and degradation of FLS2 within 1 h. Why plant cells remove this receptor precisely at the time during which its function is required remains mainly unknown. Here, we assessed in planta flg22-signaling competency in the context of ligand-induced degradation of endogenous FLS2 and chemical interference known to impede flg22-dependent internalization of FLS2 into endocytic vesicles. Within 1 h after an initial flg22 treatment, Arabidopsis (Arabidopsis thaliana) leaf tissue was unable to reelicit flg22 signaling in a ligand-, time-, and dose-dependent manner. These results indicate that flg22 induced degradation of endogenous FLS2 may serve to desensitize cells to the same stimulus (homologous desensitization), likely to prevent continuous signal output upon repetitive flg22 stimulation. In addition to impeding ligand-induced FLS2 degradation, pretreatment with the vesicular trafficking inhibitors Wortmannin or Tyrphostin A23 impaired flg22-elicited reactive oxygen species production that was partially independent of BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1. Interestingly, these inhibitors did not affect flg22-induced mitogen-activated protein kinase phosphorylation, indicating the ability to utilize vesicular trafficking inhibitors to target different flg22-signaling responses. For Tyrphostin A23, reduced flg22-induced reactive oxygen species could be separated from the defect in FLS2 degradation. At later times (>2 h) after the initial flg22 elicitation, recovery of FLS2 protein levels positively correlated with resensitization to flg22, indicating that flg22-induced new synthesis of FLS2 may prepare cells for a new round of monitoring the environment for flg22. PMID- 24220683 TI - Rethinking health services research. PMID- 24220685 TI - Explaining variation in hospice visit intensity for routine home care. AB - BACKGROUND: Medicare pays a flat per diem rate by level of hospice service without case-mix adjustment, although previous research shows that visit intensity varies considerably over the course of hospice episodes. Concerns pertain to the inherent financial incentives for routine home care, the most frequently used level, and whether payment efficiency can be improved using case mix adjustment. OBJECTIVES: The aim of this study was to assess variation in hospice visit intensity during hospice episodes by patient, hospice, and episode characteristics to inform policy discussions regarding hospice payment methods. RESEARCH DESIGN: This observational study used Medicare claims for hospice episodes in 2010. Multiple observations were constructed per episode phase (eg, days 1-14, 15-30, etc.). Episode phase and observed characteristics were regressed on average routine home care visit intensity per day; patient and hospice fixed effects controlled for unobserved characteristics. MEASURES: Visit intensity was constructed using national wages to weight visits by provider type. Observed patient characteristics included age, sex, race, diagnoses, venue of care, use of other hospice levels of care, and discharge status; hospice characteristics included ownership, affiliation, size, and urban/state location. RESULTS: Visit intensity varied substantially by episode phase. This pattern was largely invariant to observed patient and hospice characteristics, which explained <4% of variation in visit intensity per day after adjusting for episode phase. Unobserved patient characteristics explained approximately 85% of remaining variation. CONCLUSIONS: These results show that case-mix adjustment based on commonly observed factors would only minimally improve hospice payment methodology. PMID- 24220684 TI - Do HIV-infected non-small cell lung cancer patients receive guidance-concordant care? AB - BACKGROUND: The incidence of lung cancer cases among HIV-infected individuals is increasing with time. It is unclear whether HIV-infected individuals receive the same care for lung cancer as immunocompetent patients because of comorbidities, the potential for interaction between antiretroviral agents and cancer chemotherapy, and concerns regarding complications related to treatment or infection. OBJECTIVES: The objective of this study was to assess the effect of HIV infection on receipt of guidance-concordant care, and its impact on overall survival among non-small cell lung cancer Medicare beneficiaries. DESIGN: The study design was a matched case-control design where each HIV patient was matched by age group, sex, race, and lung cancer stage at diagnosis with 20 controls randomly selected among those who were not HIV infected. SUBJECTS: The patients included in this study were Medicare beneficiaries diagnosed with non-small cell lung cancer between 1998 and 2007, who qualified for Medicare on the basis of age and were 65 years of age or older at the time of lung cancer diagnosis. HIV infection status was based on Medicare claims data. A total of 174 HIV cases and 3480 controls were included in the analysis. MEASURES: Odds ratios for receiving guidance-concordant care and hazard ratios for overall survival were estimated. RESULTS: HIV infection was not independently associated with the receipt of guidance-concordant care. Among stage I/II patients, median survival times were 26 and 43 months, respectively, for those with and without HIV infection (odds ratio=1.48, P=0.021). CONCLUSIONS: HIV infection was not associated with receipt of guidance-concordant care but reduced survival in early-stage patients. PMID- 24220686 TI - Conditions causing disability and current pregnancy among US women with chronic physical disabilities. AB - BACKGROUND: Growing numbers of reproductive-age US women with chronic physical disabilities (CPD) are becoming pregnant. Little is known about the health conditions causing their CPD. OBJECTIVES: To identify health conditions causing CPD among reproductive-age women and specifically among currently pregnant women. RESEARCH DESIGN: Cross-sectional, nationally representative National Health Interview Survey data from 2006 to 2011. SUBJECTS: A total of 6043 civilian, noninstitutionalized women aged 18-49 with CPD. MEASURES: National Health Interview Survey asks about various movement difficulties and their underlying causes and about current pregnancy. We used responses from 8 movement difficulty and other questions to identify women with mobility difficulties caused by chronic physical health conditions. RESULTS: Among women with CPD, 2.0% report current pregnancy, with pregnancy rates falling monotonically as CPD severity rises. Regardless of pregnancy, 20.8% report 2 causes for their CPD, and 12.7% report 3+ causes; the most common causes are arthritis, back or neck problems, and other musculoskeletal conditions. Compared with nonpregnant women, currently pregnant women report fewer causal conditions: 15.8% report 2 causes and 8.0% 3+ causes; back or neck problems are reported most frequently, followed by musculoskeletal problems and arthritis. Multivariable logistic regression analyses predicting current pregnancy controlling for age category and individual common causes of CPD found that no cause was significantly associated with higher or lower adjusted odds of pregnancy. CONCLUSION: Almost one quarter of currently pregnant women with CPD report more than one cause for their disability. Further research will needed to examine how obstetrical needs vary for depending on the cause of a pregnant woman's disability. PMID- 24220687 TI - Sanguinarine inhibits invasiveness and the MMP-9 and COX-2 expression in TPA induced breast cancer cells by inducing HO-1 expression. AB - Most complications of breast cancer are attributed to metastasis to distant organs, including lymph nodes, bone, lung and liver. Metastasis is considered the leading cause of mortality in patients with breast cancer. The emergence of anti metastatic properties in breast cancer is an important clinical phenomenon affecting long-term survival. In the present study, we investigated the anti invasive mechanism of sanguinarine by focusing on its role in inducing HO-1 in breast cancer cells. The results showed that sanguinarine inhibited TPA-induced MMP-9 and COX-2 mRNA and protein expression in a dose-dependent manner at non cytotoxic concentrations. Similarly, the MMP-9 enzymatic activity and the PGE2 levels significantly decreased in MCF-7 breast cancer cells. TIMP-1 and TIMP-2, specific endogenous inhibitors of MMP-9, were slightly induced by sanguinarine. Subsequent studies revealed that sanguinarine suppressed TPA-induced NF-kappaB and AP-1 activation, as well as the phosphorylation of Akt and ERK. Furthermore, sanguinarine significantly inhibited TPA-induced invasion and migration in breast cancer cells. We also demonstrated that sanguinarine induced HO-1 expression, and that the inhibition of MMP-9 and COX-2 expression and the enzymatic activity of sanguinarine were abrogated by siRNA-mediated knockdown of HO-1 expression. Thus, knockdown of endogenous HO-1 decreased TPA-induced cell invasion. Overall, the results of the present study demonstrate that HO-1 plays a pivotal role in the anti-invasive response of sanguinarine in TPA-stimulated breast cancer cells. PMID- 24220688 TI - Self administration of oxycodone by adolescent and adult mice affects striatal neurotransmitter receptor gene expression. AB - Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n=12) and of adult mice (11 weeks old, n=11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug * Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice. PMID- 24220689 TI - Dopaminergic enhancement of excitatory synaptic transmission in layer II entorhinal neurons is dependent on D1-like receptor-mediated signaling. AB - The modulatory neurotransmitter dopamine induces concentration-dependent changes in synaptic transmission in the entorhinal cortex, in which high concentrations of dopamine suppress evoked excitatory postsynaptic potentials (EPSPs) and lower concentrations induce an acute synaptic facilitation. Whole-cell current-clamp recordings were used to investigate the dopaminergic facilitation of synaptic responses in layer II neurons of the rat lateral entorhinal cortex. A constant bath application of 1 MUM dopamine resulted in a consistent facilitation of EPSPs evoked in layer II fan cells by layer I stimulation; the size of the facilitation was more variable in pyramidal neurons, and synaptic responses in a small group of multiform neurons were not modulated by dopamine. Isolated inhibitory synaptic responses were not affected by dopamine, and the facilitation of EPSPs was not associated with a change in paired-pulse facilitation ratio. Voltage-clamp recordings of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor-mediated excitatory postsynaptic currents (EPSCs) were facilitated by dopamine, but N-methyl-D-aspartate receptor-mediated currents were not. Bath application of the dopamine D1-like receptor blocker SCH23390 (50 MUM), but not the D2-like receptor blocker sulpiride (50 MUM), prevented the facilitation, indicating that it is dependent upon D1-like receptor activation. Dopamine D1 receptors lead to activation of protein kinase A (PKA), and including the PKA inhibitor H-89 or KT 5720 in the recording pipette solution prevented the facilitation of EPSCs. PKA-dependent phosphorylation of inhibitor 1 or the dopamine- and cAMP-regulated protein phosphatase (DARPP-32) can lead to a facilitation of AMPA receptor responses by inhibiting the activity of protein phosphatase 1 (PP1) that reduces dephosphorylation of AMPA receptors, and we found here that inhibition of PP1 occluded the facilitatory effect of dopamine. The dopamine-induced facilitation of AMPA receptor-mediated synaptic responses in layer II neurons of the lateral entorhinal cortex is therefore likely mediated via a D1 receptor-dependent increase in PKA activity and a resulting inhibition in PP1-dependent dephosphorylation of AMPA receptors. PMID- 24220690 TI - Fetal sulcation and gyrification in common marmosets (Callithrix jacchus) obtained by ex vivo magnetic resonance imaging. AB - The present study characterized fetal sulcation patterns and gyrification in the cerebrum of the New World monkey group, common marmosets, using a 3D T2-weighted high-resolution anatomical magnetic resonance imaging (MRI) sequence from the fixed brain at 7-tesla ex vivo. Fetal sulcation in the marmoset cerebrum began to indent the lateral fissure and hippocampal sulcus in gestational week (GW) 12, and then the following sulci emerged: the callosal and calcarine sulci on GW 15; the superior temporal sulcus on GW 17; and the circular and occipitotemporal sulci on GW 18. The degree of cortical convolution was evaluated quantitatively based on 2D MRI slices by the gyrification index (GI) and based on 3D MRI data by sulcation index (SI). Both the mean GI and SI increased from GW 16, and were closely correlated with the cortical volume and the cortical surface area during fetal periods (their correlation coefficients marked more than 0.95). After birth, both the mean GI and SI decreased slightly by 2years of age, whereas the cortical volume and surface area continuously increased. Notably, histological analysis showed that the outer subventricular zone (oSVZ) in non-sulcal regions was thicker than that in the presumptive calcarine sulcal region on GW 13, preceding the infolding of the calcarine sulcus. The present results showed definite sulcal infolding on the cerebral cortical surface of the marmosets, with similar pattern and sequence of their emergences to other higher-order primates such as macaques and humans. Differential expansion of the oSVZ may be involved in gyral convolution and sulcal infolding in the developing cerebrum. PMID- 24220691 TI - Advanced airway management simulation training in medical education: a systematic review and meta-analysis. AB - OBJECTIVE: To perform a systematic review and meta-analysis of the literature on teaching airway management using technology-enhanced simulation. DATA SOURCES: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Web of Science, and Scopus for eligible articles through May 11, 2011. STUDY SELECTION: Observational or controlled trials instructing medical professionals in direct or fiberoptic intubation, surgical airway, and/or supraglottic airway using technology-enhanced simulation were included. Two reviewers determined eligibility. DATA EXTRACTION: Study quality, instructional design, and outcome data were abstracted independently and in duplicate. DATA SYNTHESIS: Of 10,904 articles screened, 76 studies were included (n = 5,226 participants). We used random effects meta analysis to pool results. In comparison with no intervention, simulation training was associated with improved outcomes for knowledge (standardized mean difference, 0.77 [95% CI, 0.19-1.35]; n = 7 studies) and skill (1.01 [0.68-1.34]; n = 28) but not for behavior (0.52 [-0.30 to 1.34]; n = 4) or patient outcomes ( 0.12 [-0.41 to 0.16]; n = 4). In comparison with nonsimulation interventions, simulation training was associated with increased learner satisfaction (0.54 [0.37-0.71]; n = 2), improved skills (0.64 [0.12-1.16]; n = 5), and patient outcomes (0.86 [0.12-1.59]; n = 3) but not knowledge (0.29 [-0.28 to 0.86]; n = 4). We found few comparative effectiveness studies exploring how to optimize the use of simulation-based training, and these revealed inconsistent results. For example, animal models were found superior to manikins in one study (p = 0.004) using outcome of task speed but inferior in another study in terms of skill ratings (p = 0.02). Five studies comparing simulators of high versus low technical sophistication found no significant difference in skill outcomes (p > 0.31). Limitations of this review include heterogeneity (I2 > 50% for most analysis) and variation in quality among primary studies. CONCLUSIONS: Simulation based airway management curriculum is superior to no intervention and nonsimulation intervention for important education outcomes. Further research is required to fine-tune optimal curricular design. PMID- 24220692 TI - Prospective randomized trial comparing shock wave lithotripsy and flexible ureterorenoscopy for lower pole stones smaller than 1 cm. AB - In this study, we aimed to compare the success and complications of flexible ureterorenoscopy (F-URS) with its advanced technology and the accomplished method of shock wave lithotripsy (SWL) in the treatment of lower pole stones smaller than 1 cm. One hundred and forty patients were randomized as 70 undergoing SWL (Group 1) and 70 undergoing F-URS (Group 2). Patients were evaluated by plain X ray and urinary ultrasound 1 week and after 3 months following SWL. The same procedure was done for F-URS patients 1 week after surgery and after 3 months. Success rates were established the day following the procedure and after 3 months. Fragmentation less than 3 mm was considered success. Mean operative time was 44 +/- 7.4 min for Group 2 and mean fluoroscopy duration was 51 +/- 12 s. In F-URS group, all the patients were stone free after 3 months (100 %). Group 1 had 2.7 +/- 0.4 sessions of SWL. Sixty-four patients were stone free in that group after 3 months (91.5 %). The procedure yielded significant success in FURS group, even though patients underwent SWL for 2.7 +/- 0.4 sessions and F-URS for 1 session (p < 0.05). With higher success and similar complication rates, fewer sessions per treatment, and advances in technology and experience, we believe F URS has a potential to be the first treatment option over SWL in the future. PMID- 24220693 TI - HDAC inhibitor confers radiosensitivity to prostate stem-like cells. AB - BACKGROUND: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation resistant fraction. METHODS: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, alpha2beta1integrin(hi)/CD133(+)), transit-amplifying (TA, alpha2beta1integrin(hi)/CD133(-)) and committed basal (CB, alpha2beta1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. RESULTS: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. INTERPRETATION: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction. PMID- 24220694 TI - Epigenetic status of LINE-1 predicts clinical outcome in early-stage rectal cancer. AB - BACKGROUND: We evaluated the clinical prognostic value of methylation of two non coding repeat sequences, long interspersed element 1 (LINE-1) and Alu, in rectal tumour tissues. In addition to DNA methylation, expression of histone modifications H3K27me3 and H3K9Ac was studied in this patient cohort. METHODS: LINE-1 and Alu methylation were assessed in DNA extracted from formalin-fixed paraffin-embedded tissues. A pilot (30 tumour and 25 normal tissues) and validation study (189 tumour and 53 normal tissues) were performed. Histone modifications H3K27me3 and H3K9Ac were immunohistochemically stained on tissue microarrays of the study cohort. RESULTS: In early-stage rectal cancer (stage I II), hypomethylation of LINE-1 was an independent clinical prognostic factor, showing shorter patient survival (P=0.014; HR: 4.6) and a higher chance of tumour recurrence (P=0.001; HR: 9.6). Alu methylation did not show any significant correlation with clinical parameters, suggesting an active role of LINE-1 in tumour development. Expression of H3K27me3 (silencing gene expression) and H3K9Ac (activating gene expression) in relation to methylation status of LINE-1 and Alu supported this specific role of LINE-1 methylation. CONCLUSION: The epigenetic status of LINE-1, but not of Alu, is prognostic in rectal cancer, indicating an active role for LINE-1 in determining clinical outcome. PMID- 24220696 TI - Long-term use of multivitamins and risk of colorectal adenoma in women. AB - BACKGROUND: Use of multivitamins may reduce the risk of colorectal adenoma, but the duration of use needed is unclear. METHODS: We prospectively examined years of multivitamin use and risk of colorectal adenoma among 43,641 women who had a first endoscopy between 1991 and 2007 in the Nurses' Health Study II. Use of multivitamins was assessed through biennial questionnaires since 1989. RESULTS: We documented 2277 colorectal adenoma cases. Reporting multivitamin use at any time during the study period compared with never reporting its use was associated with a reduced risk of adenoma (multivariable relative risk (RR)=0.86, 95% confidence interval (CI): 0.76-0.97). There was no clear trend with duration of multivitamin use: years of use compared with never use, <= 4 years (RR=0.84, 95% CI: 0.74-0.96), 5-9 years (RR=0.89, 95% CI: 0.77, 1.02), 10-14 years (RR=0.86, 95% CI: 0.74, 1.01), 15-19 years (RR=0.85, 95% CI: 0.70, 1.02), and 20-26 years (RR=0.80, 95% CI: 0.64, 1.01); (P trend=0.87). The strongest associations (years of use vs never user) were for size of adenoma: large (>= 1 cm) <4 years (RR=0.75, 95% CI: 0.58-0.96) and in alcohol users (>= 1.4 g per day) 20-26 years (RR=0.67, 95% CI: 0.49-0.91). CONCLUSION: Our findings suggest that use of multivitamins is associated with lower risk of colorectal adenoma, even with relatively short duration of use. PMID- 24220695 TI - Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer. AB - BACKGROUND: Ovarian cancer remains a major cause of cancer mortality in women, with only limited understanding of disease aetiology at the molecular level. Granulocyte colony-stimulating factor (G-CSF) is a key regulator of both normal and emergency haematopoiesis, and is used clinically to aid haematopoietic recovery following ablative therapies for a variety of solid tumours including ovarian cancer. METHODS: The expression of G-CSF and its receptor, G-CSFR, was examined in primary ovarian cancer samples and a panel of ovarian cancer cell lines, and the effects of G-CSF treatment on proliferation, migration and survival were determined. RESULTS: G-CSFR was predominantly expressed in high grade serous ovarian epithelial tumour samples and a subset of ovarian cancer cell lines. Stimulation of G-CSFR-expressing ovarian epithelial cancer cells with G-CSF led to increased migration and survival, including against chemotherapy induced apoptosis. The effects of G-CSF were mediated by signalling via the downstream JAK2/STAT3 pathway. CONCLUSION: This study suggests that G-CSF has the potential to impact on ovarian cancer pathogenesis, and that G-CSFR expression status should be considered in determining appropriate therapy. PMID- 24220697 TI - Excision Repair Cross-Complementation group 1 (ERCC1) C118T SNP does not affect cellular response to oxaliplatin. AB - AIMS: ERCC1 is involved in the repair of oxaliplatin-induced DNA damage. Studies for the association of the C118T SNP with clinical response to treatment with platinum drugs have rendered inconsistent results. We investigated the ERCC1 C118T SNP with respect to overall and progression-free survival in patients with advanced colorectal cancer (ACC) treated with oxaliplatin and in vitro DNA repair capacity after oxaliplatin exposure. In addition we discuss discrepancies from other studies concerning ERCC1 C118T. MATERIALS AND METHODS: Progression-free survival was determined in 145 ACC patients treated with oxaliplatin-based chemotherapy in a phase 3 trial. For the in vitro studies regarding ERCC1 functionality, we transfected an ERCC1 negative cell line with 118C or 118T ERCC1. Cellular sensitivity and DNA repair capacity after exposure to oxaliplatin was examined by Sulphorodamine B growth inhibition assay, COMET assay and Rad51 foci staining. RESULTS: We found no association between ERCC1 C118T and progression-free or overall survival. In addition, transfection of either 118C or 118T restores DNA-repair capacity of UV20 cells to the same level and chemosensitivity to oxaliplatin was similar in ERCC1 118C and 118T transfected cells. CONCLUSION: This study shows that the ERCC1 C118T variants are not associated with survival in ACC patients treated with oxaliplatin or the in vitro sensitivity and DNA-repair capacity in 118C and 118T transfected cell lines. Therefore, ERCC1 C118T genotyping seems of no value in individualizing oxaliplatin based chemotherapy in ACC. PMID- 24220698 TI - Closed head injury-induced changes in brain pathophysiology assessed with near infrared structured illumination in a mouse model. AB - Use of near-infrared (NIR) structured illumination technique has recently received great interest in biomedical research and clinical studies because of its ability to perform wide-field imaging and quantitatively map changes in tissue hemodynamic properties and morphological features in a noncontact and scan free fashion. We report on the feasibility of using the same to quantitatively monitor and map changes in brain optical properties and physiological parameters pre- and post-closed head injury in a mouse model. Five anesthetized male mice underwent head injury by weight-drop model using a ~50-g cylindrical metal object falling from a height of 90 cm onto the intact scalp. During experiments, NIR structured illumination was projected on the mouse head at two spatial frequencies and six different NIR wavelengths. A CCD camera positioned perpendicular to the head recorded the diffuse-reflected light. Computer analysis performed off-line on the captured data reveals spatiotemporal changes in the distribution of brain tissue absorption and reduced scattering coefficients. Using Beer's law and Mie theory, hemodynamic (hemoglobin, oxygen saturation, and lipids) and morphological (scattering amplitude and power) changes up to 1-h post trauma were observed in comparison with baseline measurements. Functional maps of different brain properties were also generated. Following injury, we found difference in both brain hemodynamic and morphologic properties with respect to baseline levels, where in some properties, this difference was considered statistically significant. Specifically, a t-test indicates a substantial decrease in oxyhemoglobin (HbO(2)) concentration and tissue oxygen saturation (StO(2)) post-injury (p < 0.01 and p < 0.001, respectively). Overall, our preliminary results demonstrate the potential application of NIR structured illumination technique to track and spatially map changes in intact mouse brain pathophysiological parameters following head injury. PMID- 24220699 TI - A common variant at 8q24.21 is associated with renal cell cancer. AB - Renal cell carcinoma (RCC) represents between 80 and 90% of kidney cancers. Previous genome-wide association studies of RCC have identified five variants conferring risk of the disease. Here we report the results from a discovery RCC genome-wide association study and replication analysis, including a total of 2,411 patients and 71,497 controls. One variant, rs35252396[CG] located at 8q24.21, is significantly associated with RCC after combining discovery and replication results (OR=1.27, P(combined)=5.4 * 10(-11)) and has an average risk allele frequency in controls of 46%. rs35252396[CG] does not have any strongly correlated variants in the genome and is located within a region predicted to have regulatory functions in several cell lines, including six originating from the kidney. This is the first RCC variant reported at 8q24.21 and it is largely independent (r(2)<=0.02) of the numerous previously reported cancer risk variants at this locus. PMID- 24220700 TI - An evaluation of Sherwood-Gilland models for NAPL dissolution and their relationship to soil properties. AB - Predicting the longevity of non-aqueous phase liquid (NAPL) source zones has proven to be a difficult modeling problem that has yet to be resolved. Research efforts towards understanding NAPL depletion have focused on developing empirical models that relate lumped mass transfer rates to velocities and organic saturations. These empirical models are often unable to predict NAPL dissolution for systems different from those used to calibrate them, indicating that system specific factors important for dissolution are not considered. This introduces the need for a calibration step before these models can be reliably used to predict NAPL dissolution for systems of arbitrary characteristics. In this paper, five published Sherwood-Gilland models are evaluated using experimental observations from the dissolution of two laboratory-scale complex three dimensional NAPL source zones. It is shown that the relative behavior of the five models depends on the system and source zone characteristics. Through a theoretical analysis, comparing Sherwood-Gilland type models to a process-based, thermodynamic dissolution model, it is shown that the coefficients of the Sherwood-Gilland models can be related to measurable soil properties. The derived dissolution model with soil-dependent coefficients predicts concentrations identical to those predicted by the thermodynamic dissolution model for cases with negligible hysteresis. This correspondence breaks down when hysteresis has a significant impact on interfacial areas. In such cases, the derived dissolution model will slightly underestimate dissolved concentrations at later times, but is more likely to capture system-specific dissolution rates than Sherwood-Gilland models. PMID- 24220701 TI - The impact of examining the meiotic spindle by polarization microscopy on assisted reproduction outcomes. AB - OBJECTIVE: To examine the effect of submitting oocytes to polarization microscopy (PM) before intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective observational study. SETTING: University hospital in Brazil. PATIENT(S): Couples undergoing ICSI. INTERVENTION(S): PM before ICSI (PM group) compared with no PM before ICSI (No-PM group) MAIN OUTCOMES MEASURE(S): Fertilization and cleavage rates, formation of top-quality embryos (TQEs), and implantation, clinical pregnancy, miscarriage, and live-birth rates. RESULT(S): The PM group consisted of 1,000 consecutive oocytes from 201 couples submitted to PM during the year of 2008. The No-PM group consisted of 1,400 oocytes from 249 couples: 700 consecutive oocytes were retrieved before we started using PM and 700 consecutive oocytes were retrieved after we stopped using PM. In the PM group, we observed an increased fertilization rate (79.7% vs. 72.5%, PM group vs. No-PM group, respectively) but reduced cleavage rate (86.2% vs. 92.5%) and TQE formation (33.1% vs. 49.9%). Implantation (18.7% vs. 20.6%), clinical pregnancy (31.8% vs. 33.3%), miscarriage (21.9% vs. 15.7%), and live-birth (24.9% vs. 28.1%) rates were not significantly different between groups. CONCLUSION(S): Use of PM was associated with increased fertilization rate but reduced cleavage rate and TQE formation; no significant difference was observed for implantation, clinical pregnancy, or live-birth rates. PMID- 24220702 TI - Sex-related growth differences are present but not enhanced in in vitro fertilization pregnancies. AB - OBJECTIVE: To determine whether IVF modifies the effect of fetal sex on growth. DESIGN: Retrospective cohort study. SETTING: Tertiary care center and related facilities. PATIENT(S): Singleton live births without fetal/maternal comorbidities from fertile women who conceived without the use of assisted reproductive technologies and infertile women who conceived with IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was birth weight (BW). Secondary outcomes were fetal crown-rump length (CRL) in the first trimester, biparietal diameter (BPD), and estimated fetal weight (EFW) in the second trimester. RESULT(S): There were no differences in baseline characteristics between women carrying male fetuses and those carrying female fetuses in either mode of conception. In unadjusted analyses, the male-female differentials in fetal BPD and BW were more pronounced in the IVF cohort than in the unassisted cohort. In multivariable regression analysis, male BPD exceeded female BPD by 0.12 cm, male EFW exceeded female EFW by 12 g, and male BW exceeded female BW by 172 g. IVF did not have a significant effect on BPD but was associated with a 52 g increase in EFW in the midgestation. IVF was associated with an 81-g reduction in BW. IVF did not modify the magnitude of size differences between the sexes in the midgestation or at birth. CONCLUSION(S): Comparable sex-dependent differential growth occurs in unassisted and IVF pregnancies. PMID- 24220703 TI - Vaginal mifepristone for the treatment of symptomatic uterine leiomyomata: an open-label study. AB - OBJECTIVE: To evaluate the efficacy and safety of 3 months of vaginal mifepristone treatment on leiomyoma volume and related symptoms. DESIGN: Prospective, open-label, two tertiary centers, phase II clinical trial. SETTING: Two tertiary medical centers in Israel. PATIENT(S): Thirty-three enrolled women, ages 30-53 years, diagnosed with symptomatic uterine fibroids. INTERVENTION(S): Patients received 10 mg mifepristone vaginally daily for 3 months. MAIN OUTCOME MEASURE(S): Reduction in uterine leiomyoma volume. Improvement in symptoms related to uterine fibroids was assessed with the use of the "Uterine Fibroid Symptoms Quality of Life Questionnaire" (UFS-QoL). The number of bleeding days, safety, and tolerability were secondary measures. RESULT(S): Mifepristone treatment significantly reduced leiomyoma volume from 135.3 +/- 22.9 cc at enrollment to 101.2 +/- 22.4 cc after 3 months of treatment. The UFS-QoL Score significantly decreased from 20.7 +/- 0.7 at enrollment to 14.0 +/- 0.8 after 3 months of treatment. The number of bleeding days significantly decreased by 3.5 days. Endometrial biopsies showed no evidence of endometrial hyperplasia or cellular atypia. There were no major side effects during the course of the study, and treatment was well tolerated. CONCLUSION(S): Vaginal mifepristone may offer an effective treatment option for women with symptomatic uterine leiomyoma and can improve the patients' quality of life. CLINICAL TRIAL REGISTRATION NUMBER: NCT00881140. PMID- 24220705 TI - Interspecific somatic hybridization between lettuce (Lactuca sativa) and wild species L. virosa. AB - Somatic hybrids between cultivated lettuce (Lactuca sativa) and a wild species L. virosa were produced by protoplast electrofusion. Hybrid selection was based on inactivation of L. sativa with 20mM iodoacetamide for 15 min, and the inability of L. virosa protoplasts to divide in the culture conditions used. Protoplasts were cultured in agarose beads in a revised MS media. In all 71 calli were formed and 21 of them differentiated shoots on LS medium containing 0.1mg/l NAA and 0.2mg/l BA. Most regenerated plants exhibited intermediate morphology. These plants were confirmed as hybrids by isoenzyme analysis. The majority of somatic hybrids had 2n=4x=36 chromosomes, and had more vigorous growth than either parent. Hybrids had normal flower morphology, but all were sterile. PMID- 24220704 TI - Reference range for the antimullerian hormone Generation II assay: a population study of 10,984 women, with comparison to the established Diagnostics Systems Laboratory nomogram. AB - OBJECTIVE: To develop an optimal model and age-specific centiles for the decline in antimullerian hormone (AMH) as measured by the new Beckman Coulter AMH Generation II (Gen II) assay and compare this to the previous nomogram derived for the Diagnostics Systems Laboratory (DSL) assay. DESIGN: Multicenter retrospective population study, with validation of linear, biphasic linear, differential, power, and quadratic equations. SETTING: Two clinical pathology laboratories. PATIENT(S): A new cohort of 10,984 women aged 25 to 45 years old attending infertility clinics, randomly divided into a training cohort of 5,492 women and a validation cohort of 5,492 women, and an existing cohort of 9,601 women, who had contributed to the development and validation of a nomogram for AMH measured by the DSL assay. INTERVENTION(S): Serum measurement of AMH as determined by the Beckman Coulter AMH Generation II assay in 10,984 women. MAIN OUTCOME MEASURE(S): Optimal model for the decline in AMH as measured by the AMH Gen II assay with age, with age-specific 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles. RESULT(S): A quadratic model defined as (2.431 + 0.089 * Age + 0.003 * Age(2)) fitted the decline in AMH with age. The anticipated 40% increase in age-specific population values relative to the previously validated DSL assay nomogram was not observed. CONCLUSION(S): Age-specific reference ranges for the AMH gen II assay suggest a systematic shift in assay calibration since initial evaluation and commercial release of the AMH Gen II assay. PMID- 24220706 TI - Transformation of Vicia narbonensis via Agrobacterium-mediated gene transfer. AB - Shoot tips and epicotyl-segments of Vicia narbonensis were co-cultivated with Agrobacterium tumefaciens strain C58C1 pGV 3850 HPT, carrying a plasmid coding for hygromycin-phosphotransferase. On callus-induction medium containing 60 mg/l hygromycin for selection, approximately 18% of the explants produced hygromycin resistant callus. After transfer to regeneration-medium these calluses produced hygromycin-resistant and nopaline-positive somatic embryos which could be regenerated to plantlets. The integration of the T-DNA into the plant genome was confirmed by Southern analysis. PMID- 24220707 TI - Improvement of regeneration of Lycopersicon pennellii protoplasts by decreasing ethylene production. AB - Lycopersicon pennellii shoots, cultured in vitro for more than a year (type I plants) produced few viable protoplasts in contrast to shoots cultured in vitro for less than five months (type II plants). Ethylene production of both plant types was compared. The low viability of plant type I protoplasts could be correlated with high ethylene production and an increased cell sap osmolality. The ethylene action inhibitor silver thiosulphate improved protoplast yield and viability, especially when using donor tissue, germinated and cultured on medium containing silver thiosulphate (type III plants). Moreover, the choice of cell wall degrading enzymes influenced protoplast viability, since ethylene release was significantly lower using Cellulase R 10 than Cellulysin. All improvements together resulted in an efficient protocol for the isolation and regeneration of Lycopersicon pennellii protoplasts. PMID- 24220708 TI - Characterization of a maize endosperm culture expressing zein genes and its use in transient transformation assays. AB - An endosperm derived tissue culture of maize (Zea mays L.) variety A636 has been characterised for its ability to synthesize zein protein and respond to a zein gene regulatory element. Western analysis with zein specific antibodies revealed the distinct presence of zein proteins of the 15, 19 and 21 kDa classes in this tissue, in contrast to an embryo-derived Black Mexican Sweet variety tissue culture which exhibited no zein proteins. Transient transformation studies with a cauliflower mosaic virus 35S promoter and luciferase reporter gene construct demonstrate that protoplasts from this tissue culture, but not from the embryo derived culture, respond positively to the potential enhancer which is located approximately 300 base pairs upstream of the coding region in most zein genes of maize, thus establishing the usefulness of this culture for studies of tissue specific gene regulation. PMID- 24220709 TI - Efficient shoot regeneration of Brassica campestris using cotyledon explants cultured in vitro. AB - A system has been developed for efficient regeneration of shoots from Brassica campestris in vitro. Using 4-day old cotyledons with petioles as expiants and a combination of BA and NAA in the regeneration media, up to 70% of expiants produced shoots after 2 weeks in culture. The optimal conditions for regeneration were found to include a BA concentration of 2mgL(-1) and NAA concentration of 1mgL(-1). Light intensity had a profound effect on regeneration potential. The use of silver ions as an inhibitor of ethylene action reduced regeneration rates in this system. Rooting occured simultaneously with shoot formation on these media and the resultant shoots could be rooted readily on minimal medium. The genotype dependency was investigated and indicated that this method would be widely applicable to B. campestris cultivars. Regeneration of one cultivar, a high erucic acid type (R-500), was inefficient in the system described here. Histological studies indicated the development of multiple shoot primordia from the petiolar cut ends of the expiants after the initiation of meristematic activity in the cells about 100MUm from the cut site within 2 days of culture initiation. The system described is compatible with previously reported Agrobacterium - mediated transformation protocols involving cotyledonary petioles. PMID- 24220710 TI - Stable endosperm cell suspension cultures from wild-type and opaque-2 maize. AB - Stable cell suspension cultures have been established from immature endosperms of A69Y wild-type and opaque-2 maize (Zea mays L.). Cultured cells are capable of storage protein (zein) synthesis and accumulation throughout the growth period. Electrophoretic patterns of zeins show, for opaque-2 cells, the preferential inhibition of the accumulation of 22 kDa peptides typical of the mutation. Viable protoplasts, able to regenerate cell walls, as well as to divide and to express foreign DNA in transient expression experiments, can be obtained with high yields from cultures of both genotypes. PMID- 24220711 TI - High efficiency plant regeneration from cotyledons of watermelon (Citrullus vulgaris Schrad). AB - Cotyledons of various ages from seedlings of eight watermelon (Citrullus vulgaris) cultivars were cultured on MS medium supplemented with different combinations of phytohormones. High frequency shoot regeneration (60.0-92.0%) was induced from 5-day-old cotyledons of cultivars cultured on MS medium containing 5.0 mg/l 6-benzylaminopurine (BA) and 0.5 mg/l indole-3-acetic acid (IAA). Multiple shoot buds elongated on MS medium containing 0.2 mg/l kinetin (KT) and 5 10 shoots per expiant could be recovered depending on the cultivars. Elongated shoots rooted on MS medium with 0.1 mg/l alpha-naphthalene acetic acid (NAA). Zeatin riboside (ZT) had a similar efficiency as BA in shoot induction, and it was significantly more functional than 2-isopentenyladenine (2iP) or kinetin (KT). Cotyledons from 5-day-old seedlings were the most responsive to shoot induction. PMID- 24220712 TI - Regeneration of multiple shoots and plants from Mesembryanthemum crystallinum. AB - Mesembryanthemum crystallinum plants have been regenerated via organogenesis from hypocotyl, cotyledonary node, and leaf expiants with varying frequencies. The highest regeneration frequencies were obtained from either hypocotyls (23-34%) or cotyledonary nodes (21-41%). Leaf expiants yielded very poor regeneration frequencies (0-11%). Expiants were placed on Murashige and Skoog (MS) media supplemented with 3% sucrose, 0.8% bacto-agar and either, 10.8*10(-6)M NAA and 8.8*10(-6)M BA (MSmsh), 1*10(-5)M BA and 1*10(-6)M IAA, (MS4) or 1*10(-6)M BA and 1*10(-6)M IAA (MS5). Shoot formation frequencies were greater on MS4 and MS5 and lower on MSmsh, however, overall differences of regeneration frequency among media tested were not statistically significant. Regenerated plantlets were rooted on MS medium without growth regulators. Mature, regenerated plants were fertile and exhibited DNA content and ploidy profiles that were identical to wild type plants. PMID- 24220713 TI - Efficient shoot formation on internodal segments and alkaloid formation in the regenerates of Cephaelis ipecacuanha A. Richard. AB - Rapid shoot proliferation was established by adventitious shoot formation on internodal segments. Cross sections of the shoot initiation area were observed microscopically and adventitious shoots were studied under the scanning electron microscope. Shoots were directly formed on the epidermis of internodal segments in vitro without callusing, but not on that of nodal segments with axillary buds. The use of media containing 0.01 - 0.1 mg/l 6-benzyladenine or 0.1 mg /l kinetin and culture under 16 h light increased the number of shoots per segment. The shoots thus obtained were rooted on phytohormone-free Woody Plant or Gamborg B5 solid medium, and were then transferred to soil. When potted, these grew well in a greenhouse. The emetic alkaloid content of adventitious shoots and regenerated plants was determined by HPLC. In vitro shoots cultured in Woody Plant liquid medium supplemented with 0.01 - 0.1 mg/l 6-benzyladenine contained 0.04 - 0.07 % dry wt. emetine and 0.4 - 0.5 % dry wt. cephaeline. One-year old regenerated plants cultivated in a greenhouse demonstrated the same alkaloid content (roots contained 0.82 % dry wt. emetine and 2.16 % dry wt. cephaeline) as the parental plant. PMID- 24220714 TI - Direct gene transfer to protoplasts of Arabidopsis thaliana. AB - We performed a series of direct gene transfer experiments with protoplasts of Arabidopsis thaliana ecotype Zurich. An average of more than 100 transformants were selected per 10(6)6 treated protoplasts. Stable transformation was confirmed by integration of the marker gene into high molecular weight DNA and by its genetic transmission to subsequent offspring generations. PMID- 24220715 TI - Arabidopsis thaliana: protocol for plant regeneration from protoplasts. AB - We report a protocol for plant regeneration from leaf protoplasts of Arabidopsis thaliana ecotype Zurich. The protocol has been established in 1988 and has since been in routine use in our laboratory. Whereas recovery of proliferating protoplast-derived clones is routine, the success in plant regeneration from protoplast-derived clones is highly variable. In the hands of one of us (H.K.) average shoot regeneration frequency (% of calli regenerating at least one shoot) was ca. 60% and average plant regeneration frequency (% of calli yielding fertile plants in soil) was ca. 40%. PMID- 24220716 TI - Hernandulcin in hairy root cultures of Lippia dulcis. AB - The hairy root culture of Lippia dulcis Trev., Verbenaceae, was established by transformation with Agrobacterium rhizogenes A4. The transformed roots grew well in Murashige and Skoog medium containing 2% sucrose. The roots turned light green when they were cultured under 16 h/day light. The green hairy roots produced the sweet sesquiterpene hernandulcin (ca. 0.25 mg/g dry wt) together with 20 other mono- and sesquiterpenes, while no terpenes were detected in the nontransformed root cultures. The growth and hernandulcin production in the hairy root cultures were influenced by the addition of auxins to the medium. The addition of a low concentration of chitosan (0.2 - 10.0 mg / l) enhanced the production of hernandulcin 5-fold. PMID- 24220717 TI - Formation of plantlets through somatic embryogeny in the Himalayan blue poppy, Meconopsis simplicifolia (Papaveraceae). AB - Exuberant and subculturable calli could be induced from only hypocotyl and leaf segments of ca 4-month-old seedlings of Meconopsis simplicifolia cultured on Murashige & Skoog's medium supplemented with 10(-6)M kinetin + 10(-5)M alpha naphthalene acetic acid. Suspension cultures were initiated from the calli in a similar medium but with 10(-5)M 2,4-dichlorophenoxy acetic acid in place of alpha -naphthalene acetic acid. In ca 80% of the suspension cultures somatic embryos differentiated freely (80-85%) as well as on the surface of small clumps of tissue (15-20%). Somatic embryos that developed beyond heart-shaped stage were transferred to agar-solidified Murashige & Skoog's medium free of growth substances. When maintained in 10 h light and 14 h dark the somatic embryos developed into plantlets bearing cauline leaves. From seed sowing to raising normal plantlets via callus required 28 weeks; on average 80 plantlets were obtained from one explant in three passages. PMID- 24220718 TI - Nodule culture and regeneration of Eucalyptus grandis hybrids. AB - Callus of three superior Eucalyptus grandis hybrids was induced from immature inflorescences, floral parts, shoot tips, zygotic embryos, and hypocotyl explants on various auxin (2,4-D or NAA) and cytokinin (kinetin) supplemented media. Hypocotyl callus initiated on 4 mg/l NAA and 1 mg/l kinetin formed massive nodular structures, and shoots and roots after four weeks on hormone free-medium. Callus from all other expiants turned brown and died upon transfer to hormone free or reduced hormone media. The nodular structures originating from hypocotyl callus were maintained by subculture for over three years and retained the ability to form thousands of shoots. Shoots were successfully rooted (98% rooting) and plantlets developed were transferred to mist-greenhouse and then to greenhouse conditions with 95% survival. Plantlets were grown for six months in the greenhouse without sign of abnormal growth. PMID- 24220719 TI - Stable transformation of Populus and incorporation of pest resistance by electric discharge particle acceleration. AB - Three different target tissues (protoplast-derived cells, nodules, and stems) and two unrelated hybrid genotypes of Populus (P. alba x P. grandidentata 'Crandon' and P. nigra 'Betulifolia' x P. trichocarpa) have been stably transformed by electric discharge particle acceleration using a 18.7 kb plasmid containing NOS NPT, CaMV 35S-GUS, and CaMV 35S-BT. Four transformed plants of one hybrid genotype, NC5339, containing all 3 genes were recovered and analyzed. Two expressed GUS and one was highly resistant to feeding by 2 lepidopteran pests (the forest tent caterpillar, Malacosoma disstria, and the gypsy moth, Lymantria dispar.) Pretreatment of the target tissues, fine-tuning of the bombardment parameters, and the use of a selection technique employing flooding of the target tissues were important for reliable recovery of transformed plants. PMID- 24220720 TI - Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux. AB - The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by <=50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions. PMID- 24220721 TI - Evolution of viral sensing RIG-I-like receptor genes in Leporidae genera Oryctolagus, Sylvilagus, and Lepus. AB - One of the most severe European rabbit (Oryctolagus cuniculus) pathogens is myxoma virus (MYXV), a rabbit-specific leporipoxvirus that causes the highly lethal disease myxomatosis. Other leporid genera, Sylvilagus and Lepus, encompass species with variable susceptibilities to MYXV, but these do not develop the lethal form of the disease. The protective role of the retinoic acid-inducible gene-I (RIG-I/DDX58) in sensing MYXV in nonpermissive human myeloid cells prompted the study of the RIG-I-like receptor (RLR) family evolution in the three leporid genera. This viral-sensor family also includes the melanoma differentiation-associated factor 5 (MDA5/IFIH1), and the laboratory of genetics and physiology 2 (LGP2/DHX58). Considering specifically the MYXV susceptible host (European rabbit) and one of the virus natural long-term hosts (Sylvilagus bachmani, brush rabbit), the amino acid differences of positively selected sites in RIG-I between the two species were located in the protein region responsible for viral RNA recognition and binding, the repressor domain. Such differences might play a determinant role in how MYXV is sensed. When looking for episodic selection on MDA5 and LGP2 of the eastern cottontail (Sylvilagus floridanus), we also uncovered evidence of selective pressures that might be exerted by a species specific leporipoxvirus, the Shope fibroma virus. Finally, a putative alternative splicing case was identified in Oryctolagus and Lepus MDA5 isoforms, corresponding to the deletion of one specific exon. This study provided the first insights into the evolution of the leporid RLR gene family that helps illuminate the origins of the species-specific innate responses to pathogens and more specifically to MYXV. PMID- 24220722 TI - Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to topical preservatives. AB - BACKGROUND: Patients with atopic dermatitis (AD) have chronic dry skin to which they frequently apply skin care products containing preservatives, and they are predisposed to developing cutaneous delayed-type hypersensitivity. OBJECTIVE: We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD and to assess whether atopic patients in our database were more likely to patch test positive to preservatives. METHODS: A total of 2453 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reaction among patients with AD (n = 342) and without AD (n = 2111) was assessed. Statistical analysis was done using a chi(2) test. RESULTS: Compared with nonatopic patients, patients with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to quaternium-15, imidazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane 1,3-diol but not to parabens, formaldehyde, or diazolidinyl urea. LIMITATIONS: Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. CONCLUSIONS: Patients with AD should avoid the use of skin care products preserved with formaldehyde releasers. PMID- 24220724 TI - From the Medical Board of the National Psoriasis Foundation: Recommendations for screening for hepatitis B infection prior to initiating anti-tumor necrosis factor-alfa inhibitors or other immunosuppressive agents in patients with psoriasis. AB - BACKGROUND: No consensus exists regarding the optimal laboratory screening for hepatitis B infection that should be performed before initiating therapy with tumor necrosis factor-alfa inhibitors or other immunosuppressive agents. OBJECTIVE: We sought to give guidelines on which tests to order for hepatitis B screening. METHODS: We review the pathophysiology and serology of hepatitis B infection and provide recommendations for screening for hepatitis B infection in patients with psoriasis before beginning anti-tumor necrosis factor-alfa therapy or other immunosuppressive agents. RESULTS: We propose the standardized use of triple serology testing: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody in combination with liver function tests as screening. LIMITATIONS: Conclusions based on review of available literature is a limitation. CONCLUSIONS: All patients with psoriasis who are candidates for tumor necrosis factor-alfa inhibitor should undergo screening for hepatitis B virus infection using the triple serology: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody. It is advisable that patients, who are candidates for ustekinumab, cyclosporine, or methotrexate undergo the same screening. PMID- 24220723 TI - The Integrated Skin Exam film: an educational intervention to promote early detection of melanoma by medical students. AB - BACKGROUND: Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students. OBJECTIVE: We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tool's effect on knowledge, attitudes, and perceptions related to the SCE. METHODS: Second-year students among 8 randomized schools viewed the film and completed pre post questionnaires. RESULTS: After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination. LIMITATIONS: Longitudinal impact of the film was not assessed. CONCLUSION: The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE. PMID- 24220725 TI - Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-kappaB. AB - Since multidrug resistance (MDR) is one of the main reasons for failure in cancer treatment, its suppression may increase the efficacy of cancer therapy. In the present study we attempted to identify a new and effective anticancer drug against MDR cancer cells. We first found that lung cancer A549 cells resistant to etoposide (A549RT-eto) exhibit upregulation of NF-kappaB and SIRT1 in comparison to A549 parental cells. During a search for anticancer drug candidates from medicinal plant sources, we found that an extract fraction (F14) of Bryophyllum laetivirens leaves downregulated expression of NF-kappaB and SIRT1, sensitizing the levels of A549RT-eto cells to apoptosis through downregulation of P glycoprotein (P-gp), which is encoded by the MDR1 gene. To address whether NF kappaB is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with Bay11-7802, an inhibitor of NF-kappaB. We then observed that Bay11 7802 treatment reduced P-gp expression levels, and furthermore combined treatment with the F14 extract and Bay11-7802 accelerated apoptosis through a decrease in P gp levels, suggesting that NF-kappaB is involved in MDR. To address whether upregulation of SIRT1 is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with SIRT1 siRNA or nicotinamide (NAM), an inhibitor of SIRT1. we found that suppression of SIRT1 did not reduce P-gp levels. furthermore, the combined treatment with the F14 extract, and SIRT1 siRNA or NAM did not accelerate apoptosis, indicating that SIRT1 is not involved in the regulation of P-gp levels in A549RT-eto cells. Taken together, we suggest that upregulation of NF-kappaB determines etoposide resistance through P-gp expression in human A549 lung cancer cells. We herein demonstrated that B. laetivirens extract reverses etoposide resistance in human A549 lung cancer cells through downregulation of NF-kappaB. PMID- 24220726 TI - Simultaneous determination of the second-harmonic generation emission directionality and reduced scattering coefficient from three-dimensional imaging of thick tissues. AB - Second-harmonic generation (SHG) microscopy has intrinsic contrast for imaging fibrillar collagen and has shown great promise for disease characterization and diagnostics. In addition to morphology, additional information is achievable as the initially emitted SHG radiation directionality is related to subresolution fibril size and distribution. We show that by two parameter fittings, both the emission pattern (FSHG/BSHG)creation and the reduced scattering coefficient MUs', can be obtained from the best fits between three-dimensional experimental data and Monte Carlo simulations. The improved simulation framework accounts for collection apertures for the detected forward and backward components. We apply the new simulation framework to mouse tail tendon for validation and show that the spectral slope of MUs' obtained is similar to that from bulk optical measurements and that the (FSHG/BSHG)creation values are also similar to previous results. Additionally, we find that the SHG emission becomes increasingly forward directed at longer wavelengths, which is consistent with decreased dispersion in refractive index between the laser and SHG wavelengths. As both the spectral slope of MUs' and (FSHG/BSHG)creation have been linked to the underlying tissue structure, simultaneously obtaining these parameters on a microscope platform from the same tissue provides a powerful method for tissue characterization. PMID- 24220727 TI - Improving permeability and oral absorption of mangiferin by phospholipid complexation. AB - Mangiferin is an active ingredient of medicinal plant with poor hydrophilicity and lipophilicity. Many reports focused on improving aqueous solubility, but oral bioavailability of mangiferin was still limited. In this study, we intended to increase not only solubility, but also membrane permeability of mangiferin by a phospholipid complexation technique. The new complex's physicochemical properties were characterized in terms of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), aqueous solubility, oil-water partition coefficient and in vitro dissolution. The intestinal absorption of the complex was studied by the rat in situ intestinal perfusion model. After oral administration of mangiferin-phospholipid complex and crude mangiferin in rats, the concentrations of mangiferin were determined by a validated RP-HPLC method. Results showed that the solubility of the complex in water and in n-octanol was enhanced and the oil-water partition coefficient was improved by 6.2 times and the intestinal permeability in rats was enhanced significantly. Peak plasma concentration and AUC of mangiferin from the complex (Cmax: 377.66 MUg/L, AUC: 1039.94 MUg/L*h) were higher than crude mangiferin (Cmax: 180 MUg/L, AUC: 2355.63 MUg/L*h). In view of improved solubility and enhanced permeability, phospholipid complexation technique can increase bioavailability of mangiferin by 2.3 times in comparison to the crude mangiferin. PMID- 24220728 TI - In-vivo observations of a spherical aggregate of endoplasmic reticulum and of Golgi vesicles in the tip of fast-growing Chara rhizoids. AB - In-vivo differential interference contrast microscopy was used to detect individual Golgi vesicles and a new structure in the tip of fast-growing rhizoids of Chara fragilis Desvaux. This structure is a spherical clear zone which is free of Golgi vesicles, has a diameter of 5 MUm and is positioned in the center of the apical Golgi-vesicle accumulation ("Spitzenkorper"). After glutaraldehyde fixation and osmium tetroxide-potassium ferricyanide staining of the rhizoid, followed by serial sectioning and three-dimensional reconstruction, the spherical zone shows a tight accumulation of anastomosing endoplasmic reticulum (ER) membranes. The ER membranes radiate from this aggregate towards the apical plasmalemma and to the membranes of the statolith compartments. Upon gravistimulation the ER aggregate changes its position according to the new growth direction, indicating its participation in growth determination. After treatment of the rhizoid with cytochalasin B or phalloidin the ER aggregate disappears and the statoliths sediment. It is concluded that the integrity of the ER aggregate is actin-dependent and that it is related to the polar organisation of the gravitropically growing cell tip. PMID- 24220729 TI - Detection of lectins in nodulated peanut and soybean plants. AB - The direct double-antibody enzymelinked immunosorbent assay system was used in the detection and measurement of seed lectins from peanut (Arachis hypogaea L.) and soybean (Glycine max L.) plants (PSL and SBL, respectively) that had been inoculated with their respective rhizobia. Concentrations of PSL dropped to undetectable levels in peanut roots at 9 d and stems and leaves at 27 d after planting; SBL could no longer be detected in soybean roots at 9 d and in stems and leaves at 12 d. A lectin antigenically similar to PSL was first detected in root nodules of peanuts at 21 d reaching a maximum of 8 MUg/g at 29 d then decreasing to 2.5 MUg/g at 60 d. There was no evidence of a corresponding lectin in soybean nodules.Sugar haemagglutination inhibition tests with neuraminidase treated human blood cells established that PSL and the peanut nodule lectin were both galactose/lactose-specific. Further tests with rabbit blood cells demonstrated a second mannosespecific lectin in peanut nodule extracts that was not detected in root extracts of four-week-old inoculated plants or six-week-old uninoculated plants, although six-week-old root extracts from inoculated plants showed weak lectin activity. The root extracts from both nodulated and uninoculated plants contained another peanut lectin that agglutinated rabbit but not human blood cells. Haemagglutination by this lectin was, however, not inhibited by simple sugars but a glycoprotein, asialothyroglobulin, was effective in this respect. PMID- 24220730 TI - Differences in properties of peanut seed lectin and purified galactose- and mannose-binding lectins from nodules of peanut. AB - Two lectins were purified by affinity chromatography from mature peanut (Arachis hypogaea L.) nodules, and compared with the previously characterised seed lectin of this plant. One of the nodule lectins was similar to the seed lectin in its molecular weight and amino-acid composition and ability to bind derivatives of galactose. However, unlike the seed lectin, this nodule lectin appeared to be a glycoprotein and the two lectins were only partially identical in their reaction with antibodies prepared against the seed lectin. The other nodule lectin also appeared to be a glycoprotein but bound mannose/glucose-like sugar derivatives, and differed from the seed lectin in molecular weight, antigenic properties and amino-acid composition. PMID- 24220731 TI - Regulation of assimilatory nitrate reduction at the level of nitrite in Chlorella fusca. AB - Batch cultures of Chlorella fusca excreted nitrite into the medium if gassed with air (0.03% CO2), but they did not if supplied with air containing 5% CO2. After a change from high to low CO2 concentration in the gas stream, nitrite excretion started immediately. After an increase in CO2 concentration to 5%, nitrite uptake started within only 30 min. Changes of in-vitro activities of nitrate reductase, nitrite reductase and glutamine synthetase did not correspond to changes of nitrite concentration in the medium and therefore could not explain these observations. A nitrite-binding site, whose activity corresponded with both nitrite excretion and uptake, was detected at the chloroplast envelope. From these data an additional regulatory step in the assimilatory nitrate-reduction sequence is suggested. This includes an envelopeprotein fraction probably regulating the availability of nitrite within the chloroplast. PMID- 24220732 TI - Purification of tobacco O-methyltransferases by affinity chromatography and estimation of the rate of synthesis of the enzymes during hypersensitive reaction to virus infection. AB - The three tobacco (Nicotiana tabacum L.) S-adenosyl-L-methionine: o-diphenol-O methyltransferases (OMTs; EC 2.1.1.6) were purified to homogeneity by affinity chromatography on adenosine-agarose. Amounts and catalytic actities of the enzymes were measured in tobacco leaves during the hypersensitive reaction to tobacco mosaic virus. The drastic increase in activity of each enzyme upon infection was shown to arise from the accumulation of enzymatic protein with constant specific enzymatic activity. Rates of OMT synthesis were determined from pulse-labeling experiments with L-[(14)C]leucine injected into the leaves. The specific radioactivities of the homogenous enzymes were compared in healthy and tobacco mosaic virus-infected tobacco. The results demonstrated that increase in OMT amounts is a consequence of de novo synthesis of the enzymes. PMID- 24220733 TI - Kinetics of L-valine uptake in tobacco leaf discs. Comparison of wild-type, the digenic mutant Val(r)-2, and its monogenic derivatives. AB - Uptake rates of L-valine in epidermis-free leaf discs of tobacco (Nicotiana tabacum L. cv. Xanthi) were measured over the concentration range 0.1 MUM to 50 mM. Wild-type tobacco was compared with the digenic mutant Val(r)-2 (genotype vr2/vr2; vr3/vr3), and with the monogenic mutant strains h9 and h10 (genotype +/+; vr3/vr3) and h17 and h23 (genotype vr2/vr2; +/+). Rate equations consisting of one to three Michaelis-Menten terms, possibly in combination with a linear term were fitted to the kinetic data. These rate equations are equivalent to rational polynomials which may be regarded as the general type of mathematical function describing the kinetics of enzymes and carriers. Kinetic data of the four genotypes conformed to the sum of three Michaelis-Menten terms. Accordingly, three kinetic components could be distinguished. In the wild-type the approximate Kms were 40 MUM, 1mM, and 40 mM, respectively. In Val(r)-2 a component with a very low Km (about 4 MUM) was found which may represent either the modified low Km component of the wild-type or a fourth component which is undetectable in the wild-type by kinetic analysis. The Vmax of the low-Km component in Val(r)-2 was at least a 100-fold lower than in the wild-type. In the presence of one of the mutant genes the calculated Vmax of the low-Km component was 48% (strains h9 and h10) or 40% (strains h17 and h23) of the corresponding Vmax in the wild-type. It is reasoned that the mutations have no effect on the activity of the other two kinetic components, though the evidence for this is circumstantial. Autoradiographs of leaf discs showed that in Val(r)-2 the uptake of (14)C labelled valine in both mesophyll and minor veins was strongly reduced as compared with the wild-type. PMID- 24220734 TI - Compartmentation of uridine 5'-triphosphate occurs during synthesis of cytoplasmic and mitochondrial ribosomal RNAs of cultured tomato cells but not during synthesis of cytoplasmic ribosomal and transfer RNAs. AB - Compartmentation of uridine 5'-triphosphate (UTP) was studied during the nucleolar synthesis of cytoplasmic ribosomal RNA (cyt-rRNA) and the synthesis of cytoplasmic transfer RNA (cyt-tRNA) in the nuclear matrix as well as the synthesis of mitochondrial ribosomal RNA (mt-rRNA) in tomato (Lycopersicon esculentum Mill. cv. Lukullus) cell-suspension culture using the approach of Wiegers et al. (Eur. J. Biochem. 64, 535-540, 1976). Before measurements were made, it was ensured that: (i) there was steady-state labeling of all RNAs studied as well as UTP; (ii) there was stability of cyt-tRNA and cyt-rRNA; (iii) there was no label randomization through degradation of [(3)H]uridine; (iv) there were significant differences in the specific radioactivity of UTP, the final immediate precursor of RNA, after supplying the cells with two different exogenous [(3)H]uridine concentrations.By comparing the steady-state specific radioactivity of UTP with that of cyt-tRNA and cyt-18S rRNA during constant [(3)H]uridine supply, we found that the three molecules had equal specific radioactivities which, however, differed significantly from that of the mt-rRNA. With a 20-fold higher uridine concentration, i.e. a 20-fold lower specific radioactivity of exogenous [(3)H]uridine, the specific radioactivity of cyt-rRNA, cyt-tRNA and UTP decreased proportionally whereas that of mt-RNA increased. These results argue against different UTP pools during synthesis of cyt-rRNA and cyt tRNA, but indicate compartmentation of UTP during rRNA synthesis in the nucleus and the mitochondria of tomato cells. PMID- 24220735 TI - Calcium and the mechanical properties of soybean hypocotyl cell walls: Possible role of calcium and protons in cell-wall loosening. AB - The role of calcium in the mechanical strength of isolated cell walls of soybean (Glycine max (L.) Merr. cv. Wayne) hypocotyls has been investigated, using the Instron technique to measure the plastic extensibility (PEx) of methanol-boiled, bisected hypocotyl sections and epidermal strips, and atomic absorption spectroscopy to measure wall calcium. Plastic extensibility was closely correlated with the growth rate of intact soybean hypocotyls. Removal of calcium from isolated cell walls by ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N' tetraacetic acid (EGTA) or low pH increased PEx, while addition of calcium decreased PEx; both effects were reversible. The amount of calcium removed and the increase in PEx at pH 4.5 were strongly dependent upon the chelating ability of the buffer anion. There was a direct correlation between the amount of calcium removed from the wall by EGTA or acid and the increase in PEx. Removal of up to 60% of the calcium increased PEx of half-section up to two fold, but further loss of calcium caused a much greater increase in PEx. With epidermal strips, PEx increased only when calcium was reduced below a threshold. At pH 3.5, there was an additional increase in PEx after a lag of about 2 h; this additional increase may be the result of acid-induced cleavage of a different set of load-bearing bonds. We conclude that calcium bridges are part of the load-bearing bonds in soybean hypocotyl cell walls, and that breakage of these crosslinks by apoplastic acid participates in wall loosening. Acid-induced solubilization of wall calcium may be one mechanism involved in wall loosening of dicotyledonous stems. PMID- 24220736 TI - Interaction of sulfate and glutathione transport in cultured tobacco cells. AB - Photoheterotrophic and heterotrophic suspension cultures of tobacco (Nicotiana tabacum L.) were grown with 1 mM glutathione (reduced; GSH) as sole source of sulfur. Addition of sulfate to both cultures did not alter the rate of exponential growth, but affected the removal of GSH and sulfate in different ways. In photoheterotrophic suspensions, addition of sulfate caused a decline in the net uptake of GSH, whereas sulfate was taken up by the green cells immediately. In heterotrophic suspensions, however, addition of sulfate did not affect the net uptake of GSH and sulfate was only taken up by the cells after the GSH supply in the medium had been exhausted. Apparently, GSH uptake in photoheterotrophic cells is inhibited by sulfate, whereas sulfate uptake is inhibited by GSH in heterotrophic cells. The differences in the effect of GSH on sulfate uptake in photoheterotrophic and heterotrophic tobacco suspensions cannot be attributed to differences in the kinetic properties of sulfate carriers. In short-time transport experiments, both cultures took up sulfate almost entirely by an active-transport system as shown by experiments with metabolic inhibitors; sulfate transport of both cultures obeyed monophasic Michaelis-Menten kinetics with similar app. Km (photoheterotrophic cells: 16.0+/-2.0 MUM; heterotrophic cells: 11.8+/-1.8 MUM) and Vmax (photoheterotrophic cells: 323+/-50 nmol.min( 1).g(-1) dry weight; heterotrophic cells: 233+/-3 nmol.min(-1).g(-1) dry weight). Temperature- and pH-dependence of sulfate transport showed almost identical patterns. However, the cultures exhibited remarkable differences in the inhibition of sulfur influx by GSH in short-time transport experiments. Whereas 1 mM GSH inhibited sulfate transport into heterotrophic tobacco cells completely, sulfate transport into photoheterotrophic cells proceeded at more than two-thirds of its maximum velocity at this GSH concentration. The mode of action of GSH on sulfate transport in chloroplast-free tobacco cell does not appear to be direct: a 14-h exposure to 1 mM GSH was found to be necessary to completely block sulfate transport; a 4-h time of exposure did not affect this process. Consequently, glutathione does not seem to be a product of sulfur metabolism acting on sulfate carrier entities by negative feedback control. When transferred to the whole plant, the observed differences in sulfate and glutathione influx into green and chloroplast-free cells may be interpreted as a regulatory device to prevent the uptake of excess sulfate by plants. PMID- 24220737 TI - Different cell-wall components from Phytophthora megasperma f. sp. glycinea elicit phytoalexin production in soybean and parsley. AB - Different components of a crude cell-wall preparation from the phytopathogenic fungus, Phytophthora megasperma f. sp. glycinea, act as elicitors of phytoalexin accumulation in parsley (Petroselinum crispum) and soybean (Glycine max). Treatments of cultured parsley cells and protoplasts or soybean cells and cotyledons with proteinase-digested or deglycosylated elicitor preparations identify proteinaceous constituents as active eliciting compounds in parsley, which are inactive in soybean. The proteinase-treated elicitor as well as a defined heptaglucan are active in soybean but do not stimulate phytoalexin synthesis in parsley. Soybean and parsley cells therefore not only perceive different signals from cell walls of Phytophthora megasperma f. sp. glycinea, but are unable to respond to the fungal compounds primarily recognized by the other plant. PMID- 24220738 TI - Alkaloid N-oxides as transport and vacuolar storage compounds of pyrrolizidine alkaloids in Senecio vulgaris L. AB - Cell-suspension cultures of pyrrolizidinealkaloid-producing species selectively take up and accumulate senecionine (sen) and its N-oxide (sen-Nox). Cultures established from non-alkaloid-producing species are unable to accumulate the alkaloids. The uptake and accumulation of (14)C-labelled alkaloids was studied using a Senecio vulgaris cell-suspension culture as well as protoplasts and vacuoles derived from it. The alkaloid uptake exhibits all characteristics of a carrier-mediated transport. The uptake of sen-Nox follows a multiphasic saturation kinetics. The Km-values for sen Nox of 53 MUM and 310 MUM are evaluated. Senecionine competitively inhibits sen-Nox uptake, indicating that the tertiary alkaloid and its N-oxide share the same membrane carrier. The N-oxide of sen shows a pH optimum below 5.5, whereas sen is taken up over a range from pH 4 to 8. Activation energies of 90 and 53 kJ.mol(-1) are calculated for sen-Nox and sen transport, respectively. At concentrations of 10 to 100 MUM, sen-Nox is rapidly taken up by cells and protoplasts; within 2 h >90% of total N-oxide is within the cells. By contrast the uptake of sen is less efficient. Vacuoles isolated from protoplasts preloaded with sen-Nox totally retained the alkaloid N oxide, whereas sen is rapidly lost during the procedure of vacuole preparation. N oxidation converts the weak lipophilic tertiary base into a charged polar molecule which is excellently adapted to serve as the cellular transport and storage form of pyrrolizidine alkaloids. PMID- 24220739 TI - Calcium-dependent protein kinase from apple fruit membranes is calmodulin independent but has calmodulin-like properties. AB - Crude Ca(2+)-activated protein kinase from membranes of apple (Malus domestica L. Borkh., Cox's Orange Pippin) fruit can be partially purified to yield a Ca(2+) dependent protein kinase whose activity is apparently not regulated by calmodulin. The autophosphorylating catalytic subunit of this protein kinase shows a Ca(2+)-dependent mobility shift of approx. 10 kilodaltons (kDa) on sodium dodecyl sulphate-polyacrylamide gel electrophoresis; in the absence of added Ca(2+) or ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) its apparent molecular mass is approx. 50 kDa. The Ca(2+)-dependent protein kinase is inhibited by the calmodulin antagonists N-(6-aminohexyl)-5 chloro-1-naphthalenesulphonamide and trifluoperazine with IC50 values of approx. 45 MUM and 15 MUM, respectively. These similarities between the protein kinase and calmodulin indicate that the kinase may be a calmodulin-like protein. PMID- 24220740 TI - Calcium influx at the plasmalemma of Chara corallina. AB - Influx of (45)Ca into internodal cells of Chara corallina has been measured, using short uptake times, and a wash in ice-cold La(3+)-containing pondwater after the labelling period to overcome the difficulty of distinguishing extracellular tracer from that in the cell. Over 5-15 min the uptake was linear with time, through the origin. The basal influx from 0.1 mM Ca(2+) externally was 0.25-0.5 pmol.cm(-2).s(-1), but some batches of cells showed higher fluxes. The influx was markedly stimulated by depolarisation in pondwater containing 20 mM K(+). In cells in which the control flux was less than about 0.5 pmol.cm(-2).s( 1) there was no effect of 50 MUM nifedipine. In cells in which the control flux was greater than about 0.5 pmol.cm(-2).s(-1) (whether by natural variability, pretreatment, or by depolarisation in 20 mM K(+)), the flux was reduced by 50 MUM nifedipine to a value in the range 0.25-0.59 pmol.cm(-2).s(-1). It is suggested that two types of Ca-channel are probably involved, both opening on depolarisation, but only one sensitive to nifedipine. The flux was inhibited by 10 MUM BAY K 8644, which in animal cells more commonly opens Ca-channels. The apparent influx measured over long uptake times was much reduced, and the kinetics indicated filling a pool of apparent size about 1.45 nmol.cm(-2) with a halftime of about 38 min, probably representing cytoplasmic stores. It is argued that in spite of the very small pool of (free+bound) cytoplasmic Ca(2+) the measured influx is a reasonable estimate of the influx at the plasmalemma. PMID- 24220741 TI - Mechanism of rapid suppression of cell expansion in cucumber hypocotyls after blue-light irradiation. AB - Rapid suppression of hypocotyl elongation by blue light in cucumber (Cucumis sativus L.) was studied to examine possible hydraulic and wall changes responsible for diminished growth. Cell-sap osmotic pressure, measured by vaporpressure osmometry, was not decreased by blue light; turgor pressure, measured by the pressureprobe technique, remained constant during the growth inhibition; and stem hydraulic conductance, measured by dynamic and static methods, was likewise unaffected by blue light. Wall yielding properties were assessed by the pressure-block technique for in-vivo stress relaxation. Blue light reduced the initial rate of relaxation by 77%, but had little effect on the final amount of relaxation. The results demonstrate that blue irradiation acts to decrease the wall yielding coefficient, but not the yield threshold. Stress strain (Instron) analysis showed that irradiation of the seedlings had little effect on the mechanical extensibilities of the isolated wall. The results indicate that blue light can reduce cell-wall loosening without affecting bulk viscoelastic properties, and indicate a chemorheological mechanism of cell-wall expansion. PMID- 24220742 TI - Phosphate sequestration by glycerol and its effects on photosynthetic carbon assimilation by leaves. AB - Glycerol induced a limitation on photosynthetic carbon assimilation by phosphate when supplied to leaves of barley (Hordeum vulgare L.) and spinach (Spinacia oleracea L.). This limitation by phosphate was evidenced by (i) reversibility of the inhibition of photosynthesis by glycerol by feeding orthophosphate (ii) a decrease in light-saturated rates of photosynthesis and saturation at a lower irradiance, (iii) the promotion of oscillations in photosynthetic CO2 assimilation and in chlorophyll fluorescence, (iv) decreases in the pools of hexose monophosphates and triose phosphates and increases in the ratio of glycerate-3-phosphate to triose phosphate, (v) decreased photochemical quenching of chlorophyll fluorescence, and increased non-photochemical quenching, specifically of the component which relaxed rapidly, indicating that thylakoid energisation had increased. In barley there was a massive accumulation of glycerol-3-phosphate and an increase in the period of the oscillations, but in spinach the accumulation of glycerol-3-phosphate was comparatively slight. The mechanism(s) by which glycerol feeding affects photosynthetic carbon assimilation are discussed in the light of these results. PMID- 24220743 TI - Multiple molecular forms of beta-amylase in seeds and vegetative tissues of barley. AB - The molecular forms of beta-amylase present in developing, mature, germinating and malted grains of barley (Hordeum vulgare L.), and in vegetative tissues, have been studied using Western-blot analyses and isoelectric focusing of isoenzymes. Five isoforms with different relative molecular masses (Mrs) could be recognised. The major isoform present in the mature grain, called isoform B, had an Mr of about 60 000. This was converted on malting or germination to two lower-Mr forms called C and D. Previous work (R. Lundgard and B. Svensson, 1986, Carlsberg Res. Commun. 51, 487-491) has shown that these result from partial proteolysis of isoform B. Isoenzyme analyses showed complex patterns of bands, with pIs between about 5.0 and 6.0. Two allelic types were present in the eight lines. A number of new bands with a range of pIs appeared during germination and malting.An isoform with the same Mr as D and a minor low-Mr isoform (E) were present in young developing whole caryopses (8-12 d after anthesis), but not in older developing endosperms (14-21 d after anthesis). Isoenzyme analyses also showed different patterns of bands in these two tissues, while hybrid-dot analyses indicated the presence of separate populations of mRNAs. It is suggested that the early endosperm isoforms (D and E) are "green" beta-amylases present in the pericarp and-or testa of the young caryopses.Roots but not shoots or leaves also contained an isoform with the same Mr as D, although the pattern of isoenzymes differed from that present in the seed tissues.The fifth isoform, A, was a diffuse high-Mr form present in small amounts in all seed and vegetative tissues, and may correspond to a constitutively expressed form.These multiple molecular forms of beta-amylase are discussed in relation to the recent report that beta-amylase is encoded by two structural loci, with a total copy number of two to three per haploid genome (Kreis et al, 1988, Genet. Res. Camb. 51, 13-16). PMID- 24220744 TI - Biosynthesis of gallotannins. Enzymatic conversion of 1,6-digalloylglucose to 1,2,6-trigalloylglucose. AB - Cell-free extracts from Rhus typhina L. (staghorn sumach) leaves were found to catalyze the transfer of the galloyl moiety of beta-glucogallin (1-O-galloyl-beta D-glucose) to 1,6-di-O-galloyl-beta-D-glucose, resulting in the specific formation of 1,2,6-tri-O-galloyl-beta-D-glucose, an intermediate of gallotannin biosynthesis. The reaction product was unequivocally identified by co chromatography with authentic references using reversed-phase high-performance liquid chromatography and by (1)H-nuclear-magnetic-resonance spectroscopy. PMID- 24220745 TI - Tourniquet used in anterior cruciate ligament reconstruction: a system review. AB - PURPOSE: To identify whether routine use of a tourniquet is a better choice for anterior cruciate ligament reconstruction. METHOD: We searched Amed, British Nursing Index, Embase, Pubmed, Scopus, Cochrane Library and Google Scholar. We used revised Jadad score to evaluate the trial quality. Each reference list was viewed for any ignored studies. Two reviews independently extracted data from all eligible trials, including study design, patients' characteristics, interventions and outcomes. The available data were using random effects models with mean differences for continuous variables. RESULTS: The only meta-analysis indicated there was no significant difference in operative time between the tourniquet and non-tourniquet groups (mean differences -5.71, 95 % CI -12.40, 0.99). The remaining outcomes had variations in the outcome measures, so it was not possible to perform meta-analysis. CONCLUSIONS: There was insufficient evidence to support the hypothesis that patients would benefit from routinely applying a tourniquet. More high-quality randomized controlled trials were needed to test the result. PMID- 24220746 TI - Surgical treatment of chronic acromioclavicular joint dislocation using the Weaver-Dunn procedure augmented by the TightRope(r) system. AB - BACKGROUND: Variable outcomes resulting from the availability of multiple techniques for the treatment of chronic acromioclavicular joint (ACJ) dislocation have led to difficulty in choosing the optimal therapeutic strategy. Accordingly, the authors describe a technique for the treatment of chronic ACJ dislocation and its benefits. SUBJECTS AND METHODS: The authors present a technique for surgically treating chronic ACJ dislocation using the Weaver-Dunn procedure in combination with a commercially available system (TightRope; Arthrex, Naples, FL, USA). Nine patients with chronic ACJ dislocation were surgically treated and postoperative results were evaluated. RESULTS: The patients were followed up for a mean of 20 months. Shoulder function was evaluated using the Constant score, with a mean score of 97%. Compared with the uninjured side, radiography showed anatomical repositioning in the vertical plane in seven cases and slight loss of reduction in two cases. The procedure provided good functional and subjective results. All patients returned to their pre-injury activity levels. CONCLUSION: The Weaver-Dunn procedure augmented by the TightRope system appeared to be an effective for treating chronic ACJ dislocation and led to excellent outcomes in terms of return to pre-injury level of function. PMID- 24220747 TI - Distraction-free ankle arthroscopy for anterolateral impingement. AB - The origin of chronic pain after external ankle sprain is better known with arthroscopy's contribution. Chronic hypertrophic synovitis of the anterolateral ankle region is seemingly the cause, resulting in "anterolateral ankle impingement." But is partial synovectomy with fibrosis resection under arthroscopy always possible without any distraction? Are results affected? This retrospective study concerned only patients with soft tissue ankle impingement. All cases with bone and joint diseases were excluded. The final sample of 24 patients had a mean age of 35 years (21-54 years) and presented anterolateral mechanical pain associated with oedema following external ankle sprain. Medical and rehabilitative treatment was undertaken for more than 6 months before arthroscopy. Average time between trauma and arthroscopy was 21 months (5-60 months). Clinical examination revealed no ankle instability or laxity. Debridement with joint lavage was systematically performed under arthroscopy without any distraction. Average patient follow-up was 22 months (12-92 months). All patients had a good Kitaoka score, with 22 patients registering excellent results. There were no septic complications or algodystrophy. Two transient hypoesthesias were observed in the dorsal surface and lateral border of the foot with full postoperative recovery at 6 months. Distraction was never used and simple dorsiflexion was sufficient to perform arthroscopic debridement. In this study, anterolateral ankle impingement diagnosis was primarily clinical. Arthroscopic treatment yielded significant benefits on pain, oedema and resumption of sport activities. Arthroscopic treatment of anterolateral ankle impingements is thus possible with simple dorsiflexion and no distraction, resulting in a possible decrease in complication rates. Level of evidence Retrospective cohort study, Level IV. PMID- 24220748 TI - Does timing of surgery affect the outcome of open articular distal humerus fractures. AB - BACKGROUND: Open intraarticular distal humerus fractures classified as Orthopaedic Trauma Association (OTA) 13 C may have devastating consequences for patient's quality of life, especially if leading arm in younger active patient is involved. We conducted a study to determine whether the timing of open reduction and internal fixation of open intraarticular distal humerus fractures affects the outcomes. PATIENTS AND METHODS: Multicentric prospective study: In the first group, there were 15 patients, 10 men and 5 women, mean age 38.7 years, operated in <6 h of injury. In the second group 17 patients, 11 men and 6 women, mean age 42.3 years operatively treated in delayed settings, mean delay to operation 4.6 days of injury. In both groups, patients had open distal humerus articular metaphyseal multifragmentary fractures classified as OTA 13.C2 or 13.C3. Functional outcome was assessed with Mayo elbow performance score and Disabilities of Arm and Shoulder and Hand (DASH). Mean Mayo elbow performance (MEP) score in the first group was 71 (range 30-100); in the second, mean MEP was 64.3 (range 25-100). The mean DASH in the first group was 27.89 (range from 1.7 to 75.8), and in the second, mean DASH score was 32.6 (range 5.8-77.5). There were no statistically significant differences between two groups, MEP t(28)=0.935, p<0.358; DASH t(28)=-0.636, p<0.530. CONCLUSION: Our study shows that early open reduction and internal fixation of open distal articular humerus fractures reduces the hospital stay, but does not significantly affect the overall outcomes and complications. PMID- 24220749 TI - Efficacy of celecoxib for pain management after arthroscopic surgery of hip: a prospective randomized placebo-controlled study. AB - The present work was conducted to examine whether celecoxib, a selective COX-2 inhibitor, 200 mg administered 1 h preoperatively to patients undergoing arthroscopic hip surgery reduces postoperative pain. Fifty-three patients undergoing arthroscopic hip surgery under spinal anesthesia were randomized to receive either 200 mg of celecoxib (Group I) or 200 mg of placebo (Group II) 1 h preoperatively. Narcotic use was monitored for 24 h, and time in recovery room was determined. Visual analog scale (VAS) scores and Short-Form 12 (SF-12), including a physical composite score (PCS) and a mental composite score (MCS), documented pain in recovery, 12 h postoperatively, and 24 h postoperatively. Moreover, time in recovery room was also investigated. We enrolled 27 patients in Group I and 26 patients in Group II. Groups were comparable for patient characteristics. No significant difference was detected in terms of VAS scores and SF-12 in recovery room. Statistically, patients in Group I showed significantly lower pain VAS scores at 12 and 24 h postoperatively. Patients taking celecoxib had significantly higher PCS at 12 and 24 h postoperatively. No difference occurred between groups for the MCS. Patients taking celecoxib also showed a significant reduction in postoperative narcotic consumption. The obtained results from the current study indicate that patients who took celecoxib 200 mg 1 h before arthroscopic hip surgery had a less painful and more rapid recovery. Celecoxib 200 mg as a single preoperative dose could be considered as part of a perioperative analgesic plan in arthroscopic hip surgery. PMID- 24220750 TI - Expression of IGFBP-6 in proliferative vitreoretinopathy rat models and its effects on retinal pigment epithelial-J cells. AB - Proliferative vitreoretinopathy (PVR) is one of the most common causes for failed retinal detachment surgeries. The aim of the present study was to investigate the role of insulin-like growth factor-binding protein-6 (IGFBP-6) in PVR using rat models and its effects on retinal pigment epithelial-J (RPE-J) cells. PVR Wistar rat models were administered intravitreal injection of RPE-J cells (1x106/5 ul) combined with platelet-rich plasma (1x107/5 ul). The concentration of IGFBP-6 in the vitreous and serum of rats was tested by an enzyme-linked immunosorbent assay and the expression of IGFBP-6 mRNA in the liver and retina of rats was determined by quantitative polymerase chain reaction (qPCR). The expression of IGFBP-6 mRNA in the RPE-J cells stimulated by vitreous or serum from PVR patients or normal volunteers was also determined by qPCR. The proliferation of RPE-J cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 sulfophenyl)-2H-tetrazolium, inner salt (MTS) method. The success rate of PVR rat model induction at the 8th week was 89.5% (34/38). The concentration of IGFBP-6 in the vitreous and serum of PVR rats was significantly higher than that of the control group (P<0.05). The expression of IGFBP-6 mRNA in the retina of PVR rats was also significantly higher compared with the control group (P<0.05). The vitreous from PVR patients and donors significantly stimulated the expression of IGFBP-6 mRNA in the RPE-J cells (P<0.05). IGFBP-6 only inhibited IGF-II stimulated proliferation but not the basal level of proliferation or the PDGF/VEGF-stimulated RPE-J cell proliferation. Thus, the trends and effects of IGFBP-6 provide the possibility of PVR therapeutic targets, with the vitreous representing a significant environmental factor in the progression of PVR. PMID- 24220751 TI - Microbicide dosage forms. AB - Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers. PMID- 24220752 TI - Incidence of contrast-induced nephropathy in hospitalised patients with cancer. AB - OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. KEY POINTS: * Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. * CIN occurs more often when CT is performed <45 days after chemotherapy. * Hypertension and treatment with bevacizumab appear to be additional risk factors. PMID- 24220753 TI - Median nerve stiffness measurement by shear wave elastography: a potential sonographic method in the diagnosis of carpal tunnel syndrome. AB - OBJECTIVES: To measure the median nerve (MN) stiffness by quantitative shear wave elastography (SWE) at the carpal tunnel inlet and to determine whether SWE can be used in the diagnosis of carpal tunnel syndrome (CTS). METHODS: The study included 37 consecutive patients (60 wrists) with a definitive diagnosis of CTS and 18 healthy volunteers (36 wrists). The MN cross-sectional area (CSA) by ultrasound and stiffness by SWE were studied. The difference between CTS patients and controls, and the difference among subgroups based on electrodiagnostic tests were studied by the Student's t test. Interobserver variability and ROC analysis were performed. RESULTS: The MN stiffness was significantly higher in the CTS group (66.7 kPa) when compared to controls (32.0 kPa) (P < 0.001), and higher in the severe or extreme severity group (101.4 kPa) than the mild or moderate severity group (55.1 kPa) (P < 0.001). A 40.4-kPa cut-off value on SWE revealed sensitivity, specificity, PPV, NPV and accuracy of 93.3%, 88.9%, 93.3%, 88.9% and 91.7%, respectively. Interobserver agreement was excellent for SWE measurements. CONCLUSIONS: Median nerve stiffness at the carpal tunnel inlet is significantly higher in patients with carpal tunnel syndrome, for whom shear wave elastography appears to be a highly reproducible diagnostic technique. KEY POINTS: * Clinical examination is important for diagnosis of carpal tunnel syndrome * Shear wave elastography (SWE) offers new clinical opportunities within diagnostic ultrasound * SWE is highly reproducible in evaluation of median nerve stiffness * Median nerve stiffness is significantly increased in carpal tunnel syndrome * Elastography could become useful in diagnosis of carpal tunnel syndrome. PMID- 24220754 TI - Free-breathing contrast-enhanced T1-weighted gradient-echo imaging with radial k space sampling for paediatric abdominopelvic MRI. AB - OBJECTIVE: To compare the image quality of contrast-enhanced abdominopelvic 3D fat-suppressed T1-weighted gradient-echo imaging with radial and conventional Cartesian k-space acquisition schemes in paediatric patients. METHODS: Seventy three consecutive paediatric patients were imaged at 1.5 T with sequential contrast-enhanced T1-weighted Cartesian (VIBE) and radial gradient echo (GRE) acquisition schemes with matching parameters when possible. Cartesian VIBE was acquired as a breath-hold or as free breathing in patients who could not suspend respiration, followed by free-breathing radial GRE in all patients. Two paediatric radiologists blinded to the acquisition schemes evaluated multiple parameters of image quality on a five-point scale, with higher score indicating a more optimal examination. Lesion presence or absence, conspicuity and edge sharpness were also evaluated. Mixed-model analysis of variance was performed to compare radial GRE and Cartesian VIBE. RESULTS: Radial GRE had significantly (all P < 0.001) higher scores for overall image quality, hepatic edge sharpness, hepatic vessel clarity and respiratory motion robustness than Cartesian VIBE. More lesions were detected on radial GRE by both readers than on Cartesian VIBE, with significantly higher scores for lesion conspicuity and edge sharpness (all P < 0.001). CONCLUSION: Radial GRE has better image quality and lesion conspicuity than conventional Cartesian VIBE in paediatric patients undergoing contrast enhanced abdominopelvic MRI. KEY POINTS: * Numerous techniques are required to provide optimal MR images in paediatric patients. * Radial free-breathing contrast-enhanced acquisition demonstrated excellent image quality. * Image quality and lesion conspicuity were better with radial than Cartesian acquisition. * More lesions were detected on contrast-enhanced radial than on Cartesian acquisition. * Radial GRE can be used for performing abdominopelvic MRI in paediatric patients. PMID- 24220755 TI - Accuracy and efficacy of percutaneous biopsy and ablation using robotic assistance under computed tomography guidance: a phantom study. AB - OBJECTIVE: To compare the accuracy of a robotic interventional radiologist (IR) assistance platform with a standard freehand technique for computed-tomography (CT)-guided biopsy and simulated radiofrequency ablation (RFA). METHODS: The accuracy of freehand single-pass needle insertions into abdominal phantoms was compared with insertions facilitated with the use of a robotic assistance platform (n = 20 each). Post-procedural CTs were analysed for needle placement error. Percutaneous RFA was simulated by sequentially placing five 17-gauge needle introducers into 5-cm diameter masses (n = 5) embedded within an abdominal phantom. Simulated ablations were planned based on pre-procedural CT, before multi-probe placement was executed freehand. Multi-probe placement was then performed on the same 5-cm mass using the ablation planning software and robotic assistance. Post-procedural CTs were analysed to determine the percentage of untreated residual target. RESULTS: Mean needle tip-to-target errors were reduced with use of the IR assistance platform (both P < 0.0001). Reduced percentage residual tumour was observed with treatment planning (P = 0.02). CONCLUSION: Improved needle accuracy and optimised probe geometry are observed during simulated CT-guided biopsy and percutaneous ablation with use of a robotic IR assistance platform. This technology may be useful for clinical CT-guided biopsy and RFA, when accuracy may have an impact on outcome. KEY POINTS: * A recently developed robotic intervention radiology assistance platform facilitates CT guided interventions. * Improved accuracy of complex needle insertions is achievable. * IR assistance platform use can improve target ablation coverage. PMID- 24220756 TI - Characterization of hyperbranched glycopolymers produced in vitro using enzymes. AB - Asymmetrical flow field flow fractionation (AF4) has proven to be a very powerful and quantitative method for the determination of the macromolecular structure of high molar mass branched biopolymers, when coupled with multi-angle laser light scattering (MALLS). This work describes a detailed investigation of the macromolecular structure of native glycogens and hyperbranched alpha-glucans (HBPs), with average molar mass ranging from 2 * 10(6) to 4.3 * 10(7) g mol(-1), which are not well fractionated by means of classical size-exclusion chromatography. HBPs were enzymatically produced from sucrose by the tandem action of an amylosucrase and a branching enzyme mimicking in vitro the elongation and branching steps involved in glycogen biosynthesis. Size and molar mass distributions were studied by AF4, coupled with online quasi-elastic light scattering (QELS) and transmission electron microscopy. AF4-MALLS-QELS has shown a remarkable agreement between hydrodynamic radii obtained by online QELS and by AF4 theory in normal mode with constant cross flow. Molar mass, size, and dispersity were shown to significantly increase with initial sucrose concentration, and to decrease when the branching enzyme activity increases. Several populations with different size range were observed: the amount of small size molecules decreasing with increasing sucrose concentration. The spherical and dense global conformation thus highlighted was partly similar to native glycogens. A more detailed study of HBPs synthesized from low and high initial sucrose concentrations was performed using complementary enzymatic hydrolysis of external chains and chromatography. It emphasized a more homogeneous branching pattern than native glycogens with a denser core and shorter external chains. PMID- 24220757 TI - N-glycosidase treatment with 18O labeling and de novo sequencing argues for flagellin FliC glycopolymorphism in Pseudomonas aeruginosa. AB - In prokaryote organisms, N-glycosylation of proteins is often correlated to cell cell recognition and extracellular events. Those glycoproteins are potential targets for infection control. To date, many surface-glycosylated proteins from bacterial pathogens have been described. However, N-linked Pseudomonas surface associated glycoproteins remain underexplored. We report a combined enrichment and labeling strategy to identify major glycoproteins on the outside of microorganisms. More precisely, bacteria were exposed to a mix of biotinylated lectins able to bind with glycoproteins. The latter were then recovered by avidin beads, digested with trypsin, and submitted to mass spectrometry. The targeted mixture of glycoproteins was additionally deglycosylated in the presence of H2(18)O to incorporate (18)O during PNGase F treatment and were also analyzed using mass spectrometry. This approach allowed us to identify a few tens of potential N-glycoproteins, among which flagellin FliC was the most abundant. To detect the possible sites of FliC modifications, a de novo sequencing step was also performed to discriminate between spontaneous deamidation and N-glycan loss. This approach led to the proposal of three potential N-glycosylated sites on the primary sequence of FliC: N26, N69, and N439, with two of these three asparagines belonging to an N-X-(S/T) consensus sequence. These observations suggest that flagellin FliC is a heterogeneous protein mixture containing both O- and N glycoforms. PMID- 24220758 TI - Evidence-based reform of teaching and learning. AB - Over the years a great deal of time and attention has been devoted to reform of teaching and learning in chemistry. However, many of these efforts have focused on individual faculty's experiences and intuition, rather than our understanding of how people learn or evidence about the effects of such reforms. For example, while it is widely known that students emerge from our courses with non scientific ideas about core concepts, the reasons why this happens are often ascribed to the students' lack of ability or work ethic. However, there is emerging evidence that both the traditional pedagogical approach and the structure of the curriculum contribute to this problem. Students must be provided both with a strong foundation on which to build and link new knowledge, and an understanding of what that knowledge will be used for. In order to achieve this we need to rely on the research base and evidence emerging from discipline-based education research (DBER)-a field that combines deep disciplinary expertise with knowledge and understanding of the science of teaching and learning. This paper presents a short overview of these ideas. PMID- 24220759 TI - Amperometric bienzyme screen-printed biosensor for the determination of leucine. AB - Leucine plays an important role in protein synthesis, brain functions, building muscle mass, and helping the body when it undergoes stress. Here, we report a new amperometric bienzyme screen-printed biosensor for the determination of leucine, by coimmobilizing p-hydroxybenzoate hydroxylase (HBH) and leucine dehydrogenase (LDH) on a screen-printed electrode with NADP(+) and p-hydroxybenzoate as the cofactors. The detection principle of the sensor is that LDH catalyzes the specific dehydrogenation of leucine by using NADP(+) as a cofactor. The product, NADPH, triggers the hydroxylation of p-hydroxybenzoate by HBH in the presence of oxygen to produce 3,4-dihydroxybenzoate, which results in a change in electron concentration at the working carbon electrode, which is detected by the potentiostat. The sensor shows a linear detection range between 10 and 600 MUM with a detection limit of 2 MUM. The response is reproducible and has a fast measuring time of 5-10 s after the addition of a given concentration of leucine. PMID- 24220760 TI - Chemical imaging of trichome specialized metabolites using contact printing and laser desorption/ionization mass spectrometry. AB - Cell transfer by contact printing coupled with carbon-substrate-assisted laser desorption/ionization was used to directly profile and image secondary metabolites in trichomes on leaves of the wild tomato Solanum habrochaites. Major specialized metabolites, including acyl sugars, alkaloids, flavonoids, and terpenoid acids, were successfully detected in positive ion mode or negative ion mode, and in some cases in both modes. This simple solvent-free and matrix-free sample preparation for mass spectrometry imaging avoids tedious sample preparation steps, and high-spatial-resolution images were obtained. Metabolite profiles were generated for individual glandular trichomes from a single Solanum habrochaites leaf at a spatial resolution of around 50 MUm. Relative quantitative data from imaging experiments were validated by independent liquid chromatography mass spectrometry analysis of subsamples from fresh plant material. The spatially resolved metabolite profiles of individual glands provided new information about the complexity of biosynthesis of specialized metabolites at the cellular resolution scale. In addition, this technique offers a scheme capable of high throughput profiling of metabolites in trichomes and irregularly shaped tissues and spatially discontinuous cells of a given cell type. PMID- 24220761 TI - Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM). AB - Targeted absolute protein quantification yields valuable information about physiological adaptation of organisms and is thereby of high interest. Especially for this purpose, two proteomic mass spectrometry-based techniques namely selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) are commonly applied. The objective of this study was to establish an optimal quantification assay for proteins with the focus on those involved in housekeeping functions and putative reductive dehalogenase proteins from the strictly anaerobic bacterium Dehalococcoides mccartyi strain CBDB1. This microbe is small and slow-growing; hence, it provides little biomass for comprehensive proteomic analysis. We therefore compared SRM and PRM techniques. Eleven peptides were successfully quantified by both methods. In addition, six peptides were solely quantified by SRM and four by PRM, respectively. Peptides were spiked into a background of Escherichia coli lysate and the majority of peptides were quantifiable down to 500 amol absolute on column by both methods. Peptide quantification in CBDB1 lysate resulted in the detection of 15 peptides using SRM and 14 peptides with the PRM assay. Resulting quantification of five dehalogenases revealed copy numbers of <10 to 115 protein molecules per cell indicating clear differences in abundance of RdhA proteins during growth on hexachlorobenzene. Our results indicated that both methods show comparable sensitivity and that the combination of the mass spectrometry assays resulted in higher peptide coverage and thus more reliable protein quantification. PMID- 24220762 TI - Analysis of mechanical contrast in optical coherence elastography. AB - Optical coherence elastography (OCE) maps the mechanical properties of tissue microstructure and has potential applications in both fundamental investigations of biomechanics and clinical medicine. We report the first analysis of contrast in OCE, including evaluation of the accuracy with which OCE images (elastograms) represent mechanical properties and the sensitivity of OCE to mechanical contrast within a sample. Using phase-sensitive compression OCE, we generate elastograms of tissue-mimicking phantoms with known mechanical properties and identify limitations on contrast imposed by sample mechanics and the imaging system, including signal-processing parameters. We also generate simulated elastograms using finite element models to perform mechanical analysis in the absence of imaging system noise. In both experiments and simulations, we illustrate artifacts that degrade elastogram accuracy, depending on sample geometry, elasticity contrast between features, and surface conditions. We experimentally demonstrate sensitivity to features with elasticity contrast as small as 1.1?1 and calculate, based on our imaging system parameters, a theoretical maximum sensitivity to elasticity contrast of 1.002?1. The results highlight the microstrain sensitivity of compression OCE, at a spatial resolution of tens of micrometers, suggesting its potential for the detection of minute changes in elasticity within heterogeneous tissue. PMID- 24220763 TI - Comparison of transcatheter arterial chemoembolization and transcatheter arterial chemotherapy infusion for patients with intermediate-stage hepatocellular carcinoma. AB - The aim of the present study was to compare clinical outcomes in patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent the following treatments: transcatheter arterial chemoembolization (TACE) using an epirubicin mitomycin-lipiodol (EML) emulsion at initial therapy (TACE group; n=145), and transcatheter chemotherapy infusion (TACI) using an EML emulsion at initial therapy (TACI group; n=81). Overall survival (OS) and treatment efficacy in the TACE and TACI groups were retrospectively compared. Prognostic factors associated with OS were examined using univariate and multivariate analyses. Treatment related mortality was also calculated. The median observation periods were 1.8 years (range, 0.2-9.0 years) in the TACE group and 2.0 years (range, 0.2-8.7 years) in the TACI group. The median survival time and the 1-, 2-, 3- and 5-year cumulative OS rates were 2.68 years and 81.5, 63.4, 43.9 and 32.7%, respectively, in the TACE group, and 2.64 years and 85.0, 60.0, 43.2 and 26.0%, respectively, in the TACI group (P=0.691). The objective response rate was significantly higher in the TACE group compared to the TACI group (80.0 vs. 66.7%; P=0.009). Using multivariate analysis, the Child-Pugh classification (P=0.017), tumor number <=5 (P=0.045) and des-gamma-carboxy prothrombin level >100 mAU/ml (P=0.002) were found to be significant predictors linked to OS. In all subgroup analyses involving Child-Pugh classification, maximum tumor size and tumor distribution, the differences in the two groups did not reach statistical significance in terms of OS. Treatment mortality was 0% in the two groups. In conclusion, patients with intermediate-stage HCC had a comparable prognosis when treated with TACI or TACE. PMID- 24220764 TI - Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease. AB - Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease. PMID- 24220765 TI - Understanding the chronic impacts of oil refinery wastewater requires consideration of sediment contributions to toxicity. AB - Previous studies at an oil refinery in Saint John, New Brunswick, Canada, found a diminished fish community downstream of the effluent outfall that appeared to be associated with periodic low dissolved oxygen concentrations due to episodic discharges of contaminated transport vessel ballast water. This study was initiated after the ballast water was removed from the effluent to further investigate the potential causes of residual effects in the study stream, Little River. We used field caging of fish, laboratory bioassays, and chemical analysis of effluents and sediments from the field site to determine if the effluent or contaminated sediments were affecting the recovery of the fish community in Little River. The field studies suggested that exposed, caged fish were affected, displaying >40 % increases in liver sizes and increased liver detoxification enzyme activity (cytochrome P450 1A, CYP1A); however, similar responses were absent in laboratory exposures that used effluent only. Adding sediments collected from the vicinity of the refinery's outfall to the laboratory bioassays reproduced some of the field responses. Chemical analyses showed high concentrations of PAHs in sediments but low concentrations in the effluent, suggesting that the PAHs in the sediment were contributing more to the impacts than the effluent. Application of effects-based monitoring is suggested as beneficial to identify impacts to fisheries where refinery effluents of this type are involved. PMID- 24220767 TI - In-situ seed production after pollination with in-vitro-matured, isolated pollen. AB - Immature tobacco (Nicotiana tabacum L.) pollen has been isolated from anthers in three distinct stages of development, including the microspore stage. In in-vitro cultures, fully functional, mature pollen was obtained. In a germination medium, this pollen produced pollen tubes. After application to stigmas in situ, the in vitro-matured pollen fertilized ovules, and seeds were produced. Genetic tests with seedlings obtained from pollinations with in-vitro-matured pollen from a transgenic plant revealed normal Mendelian segregation of two marker genes, the neomycin-phosphotransferase II gene and the nopaline-synthase gene. These results are of interest with respect to the control of self-incompatibility, cytoplasmic male sterility and pollen-allergen formation, and it offers an alternative route for gene transfer in those plants which cannot be regenerated in vitro. PMID- 24220766 TI - Are clindamycin and ciprofloxacin appropriate for the empirical treatment of diabetic foot infections? AB - The objective of this study was to determine if specific species of microorganisms are associated with severe infection and amputation in patients with a diabetic foot infection and to evaluate the effectiveness of clindamycin and ciprofloxacin in this population. A retrospective cohort study was performed at the University Medical Center Utrecht, The Netherlands, for the period January 1st 2005 to January 1st 2010. Patients with ICD-9 codes 'diabetic foot' were selected from the hospital database. We evaluated the association of Staphylococcus aureus and Gram-negative species (GNS) with severity of infection, number of amputations, and healing rates. No significant association was found between the different microorganisms and infection severity. Coinfections of GNS and S. aureus were significantly associated with amputation compared to infections with only S. aureus [p = 0.016, odds ratio (OR) 4.9, confidence interval (CI) 1.4-16.9]. The empiric antibiotic regimen of clindamycin and ciprofloxacin covered only 85 % of S. aureus and 78 % of GNS diabetic foot infections. In mild diabetic foot infection in the studied population, where methicillin-sensitive S. aureus and streptococci are the most likely pathogens, a beta-lactam antibiotic such as flucloxacillin would likely be more effective than clindamycin. In moderate and severe infections, where GNS as a causative organism cannot be safely excluded, broad-spectrum antibiotic therapy may be more adequate. PMID- 24220768 TI - Import of peroxisomal hydroxypyruvate reductase into glyoxysomes. AB - A new procedure was used to purify the peroxisomal matrix enzyme hydroxypyruvate reductase (HPR) from green leaves of pumpkin (Cucurbita pepo L.) and spinach (Spinacia oleracea L.). Monospecific antibodies were prepared against this enzyme in rabbits. Immunoprecipitation of HPR from watermelon (Citrullus vulgaris Schrad.) yielded a single protein with a subunit molecular weight of 45 kDa. Immunohistochemical labeling of HPR was found exclusively in watermelon microbodies. Isolated polyadenylated mRNA from light-grown watermelon cotyledons was injected into Xenopus laevis oocytes. The heterologous in-vivo translation product of HPR exhibited the same molecular weight as the immunoprecipitate from watermelon cotyledons, indicating the lack of a cleavable extra sequence. The watermelon HPR translated in oocytes was imported into isolated glyoxysomes from castor bean (Ricinus communis L.) endosperm and remained resistant to proteolysis after the addition of proteinase K. The HPR did not change its apparent molecular weight during sequestration; however, it may have changed its conformation. PMID- 24220769 TI - Ultrastructural indications for coexistence of symplastic and apoplastic phloem loading in Commelina benghalensis leaves : Differences in ontogenic development, spatial arrangement and symplastic connections of the two sieve tubes in the minor vein. AB - The ultrastructural ontogeny of Commelina benghalensis minor-vein elements was followed. The mature minor vein has a restricted number of elements: a sheath of six to eight mestome cells encloses one xylem vessel, three to five vascular parenchyma cells, a companion cell, a thin-walled protophloem sieve-tube member and a thick-walled metaphloem sieve-tube member. The protophloem sieve-tube member (diameter 4-5 MUm; wall thickness 0.12 MUm) and the companion cell originated from a common mother cell. The metaphloem sieve-tube member (diameter 3 MUm; wall thickness 0.2 MUm) developed from the same precursor cell as the phloem parenchyma cells. Counting the plasmodesmatal frequencies demonstrated a symplastic continuum from mesophyll to the minor-vein phloem. The metaphloem sievetube member and the phloem parenchyma cells are the termini of this symplast. The protophloem sieve-tube member and companion cell constitute an insulated symplastic domain. The symplastic route, mesophyll to metaphloem sieve tube, appears to offer a path for symplastic loading; the protophloem sieve tube may be capable of accumulation from the apoplast. A similar two-way system of loading may exist in a number of plant families. Plasmodesmograms (a novel way to depict cell elements, plasmodesmatal frequencies and vein architecture) of some other species also displayed the anatomical requirements for two routes from mesophyll to sieve tube and indicate the potential coexistence of symplastic and apoplastic loading. PMID- 24220770 TI - Formation of wheat protein bodies: Involvement of the Golgi apparatus in gliadin transport. AB - Developing wheat (Triticum aestivum L.) endosperm was examined using ultrathin sections prepared from tissues harvested at 5, 9, 16 and 25 d after flowering. Protein bodies were evident by 9 d and displayed a variety of membranous structures and inclusions. The Golgi apparatus was a prominent organelle at all stages, and by 9 d was associated with small electron-dense inclusions. By immunocytochemical techniques, gliadin (wheat prolamine) was localized within these vesicles and in homogeneous regions of protein bodies, but not in the lumen of the rough endoplasmic reticulum. The protein bodies appear to enlarge by fusion of smaller protein bodies resulting in larger, irregular-shaped organelles. The affinity of the Golgi-derived vesicles for gliadin-specific probes during the period of maximal storage-protein synthesis and deposition indicates that this organelle includes the bulk, if not all, of the gliadin produced. The involvement of the Golgi apparatus in the packaging of gliadins into protein bodies indicates a pathway which differs from the mode of prolamine deposition in other cereals such as maize, rice and sorghum, and resembles the mechanism employed for the storage of rice glutelin and legume globulins. PMID- 24220771 TI - Desensitization by red and blue light of phototropism in maize coleoptiles. AB - The effects of pretreatments with red and blue light (RL, BL) on the fluence response curve for the phototropism induced by a BL pulse (first positive curvature) were investigated with darkadapted maize (Zea mays L.) coleoptiles. A pulse of RL, giving a fluence sufficient to saturate phytochrome-mediated responses in this material, shifted the bell-shaped phototropic fluence-response curve to higher fluences and increased its peak height. A pulse of high-fluence BL given immediately prior to this RL treatment temporarily suppressed the phototropic fluence-response curve, and shifted the curve to higher fluences than induced by RL alone. The shift by BL progressed rapidly compared to that by RL. The results indicate (1) that first positive curvature is desensitized by both phytochrome and a BL system, (2) that desensitization by BL occurs with respect to both the maximal response and the quantum efficiency, and (3) that the desensitization responses mediated by phytochrome and the BL system can be induced simultaneously but develop following different kinetics. It is suggested that theses desensitization responses contribute to the induction of second positive curvature, a response induced by prolonged irradiation. PMID- 24220772 TI - Phototropic fluence-response relations for Avena coleoptiles on a clinostat. AB - Phototropism of Avena sativa L. has been characterized using a clinostat to negate the gravitropic response. The kinetics for development of curvature was measured following induction by a single pulse of blue light (BL), five pulses of BL at 20-min intervals, and this same pulsed-light regime following a 2-h red light (RL) pre-irradiation. A final curvature of about 14 degrees is expressed within 180 min following the single pulse; a final curvature of about 62 degrees in about 240 min following five pulses without pre-irradiation; and a curvature of over 125 degrees in 360 min following five pulses after the RL pre irradiation. For seedlings not pre-irradiated, the final curvature to five pulses of BL at a total fluence of 9.4 pmol.cm(-2) increases with time of darkness between pulses up to 15 min; with seedlings pre-irradiated with RL, curvature increased more slowly with time of darkness between pulses to a maximum at 35 min. The final curvature induced by a constant fluence of 9.4 pmol.cm(-2) increases linearly with time between the first pulse and last pulse of a five pulse sequence. The curvature induced by a single BL pulse with a 5-min RL co irradiation increases with fluence to a maximum of about 60 degrees at about 10 pmol.cm(-2), and then decreases to 0 degrees at about 200 pmol.cm(-2). Curvature induced by five BL pulses following a 2-h RL pre-irradiation increased with fluence from a threshold of about 0.05 pmol.cm(-2) to a maximum of 90 degrees at about 10 pmol.cm(-2), and then gradually decreased with fluence to 50 degrees at 1 000 pmol.cm(-2). Based on these data, it is concluded that the initial photoproduct formed by a BL pulse has a limited lifetime, that there is a kinetic limitation "downstream" of the photoreceptor pigment for phototropism, and that the additivive effect of pulsed BL is distinct from the potentiating effect of RL on phototropism. Thus, any degree of curvature from 0 degrees to over 90 degrees may be induced by a fluence in the ascending arm of what is traditionally called the "first positive" phototropic response. PMID- 24220773 TI - Acquisition of embryogenic potential in carrot cell-suspension cultures. AB - Embryogenic suspension cultures of domesticated carrot (Daucus carota L.) are characterized by the presence of proembryogenic masses (PEMs) from which somatic embryos develop under conditions of low cell density in the absence of phytohormones. A culture system, referred to as starting cultures, was developed that allowed analysis of the emergence of PEMs in newly initiated hypocotyl derived suspension cultures. Embryogenic potential, reflected by the number of FEMs present, slowly increased in starting cultures over a period of six weeks. Addition of excreted, high-molecular-weight, heat-labile cell factors from an established embryogenic culture considerably accelerated the acquisition of embryogenic potential in starting cultures. Analysis of [(35)S]methionine-labeled proteins excreted into the medium revealed distinct changes concomitant with the acquisition of embryogenic potential in these cultures. Analysis of the pattern of gene expression by in-vitro translation of total cellular mRNA from starting cultures with different embryogenic potential and subsequent separation of the [(35)S]methionine-labeled products by two-dimensional polyacrylamide gel electrophoresis demonstrated a small number of abundant in-vitro-translation products to be present in somatic embryos and in embryogenic cells but absent in nonembryogenic cells. Several other in-vitro-translation products were present in explants, non-embryogenic and embryogenic cells but were absent in somatic embryos. Hybridization of an embryoregulated complementary-DNA sequence, Dc3, to RNA extracted from starting cultures showed that the corresponding gene is expressed in somatic embryos and PEMs but not in non-embryogenic cells. PMID- 24220774 TI - Gene-expression programs in embryogenic and non-embryogenic carrot cultures. AB - Somatic embryogenesis can be synchronized by enriching carrot (Daucus carota L.) suspension cultures for small, dense clusters of cells termed proembryogenic masses (PEMs). Gene-expression programs of PEMs were compared with those of embryonic and mature tissues by in-vitro translation of representative mRNA populations and by nucleic-acid hybridization. Analysis of invitro-translated polypeptides by two-dimensional polyacrylamide gel electrophoresis revealed striking similarities between the mRNA populations of PEM and torpedo-stage embryos; substantial differences, however, were observed when in-vitro translation products of PEMs and torpedo embryos were compared with those of hypocotyls and leaves. Northern blots of RNA isolated from PEMs, staged embryos, and mature carrot tissues were hybridized with cDNA probes for Dc3, Dc5 and Dc13; these cDNA recombinants represent mRNAs that are regulated during carrot somatic embryogenesis. The pattern of expression of these embryo-regulated transcripts was similar in PEMs and somatic embryos but differed in other carrot tissues. These results indicate that many of the molecular processes of embryogenesis are already established in PEMs in the presence of auxin. Additional experiments indicate the utility of Dc3 as a molecular marker for the acquisition of embryogenic potential. PMID- 24220775 TI - Phototropism of maize coleoptiles Influences of light gradients. AB - The lateral fluence-rate gradients in unilaterally irradiated maize (Zea mays L.) coleoptiles were calculated on the basis of the proportions of P fr (far-red absorbing form of phytochrome) measured spectroscopically in transverse slices of the coleoptiles (top 1 cm). The results showed the occurrence of significant gradients that are wavelength-dependent. The gradient at 449 nm was steeper than those measured at 516, 534 and 551 nm, which were steeper than that measured at 665 nm. The ratios between the sides proximal and distal to the light source were, for example, 1:0.12 (449 nm), 1:0.23 (534 nm), and 1:0.28 (665 nm). Fluence response curves for coleoptile phototropism (first positive curvature produced by less than 100 s unilateral irradiation) were measured at 449, 516, 534 and 551 nm. Comparison of the threshold fluences indicated that the responsiveness to 551 nm is about 10(4.8) less than that to 449 nm. Increasing wavelengths led to a decrease in maximal curvature, which correlated with the decrease of the fluence rate ratios between the proximal and distal sides. Phototropic fluence-response curves were also measured using bilateral irradiation (449 nm). In one set of experiments, the fluence ratio was kept constant (either 1:1/2, 1:1/4 or 1:1/16) and the total fluence was varied, and in the other set the fluence applied to one side was kept constant and the fluence ratio was varied. A simple model based on the assumption that only one photoreaction occurs, and that the response is a function of the difference between the proximal and distal sides in the local photoreceptor action was tested. A fluence-response curve for this local photoreceptor action was calculated based on the fluence-rate ratio and the phototropic fluence-response curve measured for 449 nm. This curve was used, in conjunction with the measured fluence-rate ratios, as a basis for calculating phototropic fluence-response curves for other wavelengths and those for 449 nm obtained with bilateral irradiation. The calculated fluence-response curves showed excellent agreement with the experimental data. It is concluded that the threshold for maize coleoptile phototropism reflects the apparent photoconversion cross-section of the blue-light receptor whereas the maximal curvature depends on the steepness of the light gradient across the coleoptile. PMID- 24220776 TI - Isolation and characterization of thirteen new salt-soluble proteins from barley by reversed-phase high-performance liquid chromatography. AB - Thirteen new proteins from barley (Hordeum vulgare L.) have been isolated and characterized. These proteins and seven other previously known components were isolated from a 0.5-M NaCl extract of endosperm by single-step, reversed-phase, high-performance liquid chromatography, using a Vydac C4 semi-preparative column. The purity of the isolated proteins was analyzed by polyacrylamide gel electrophoresis at pH 3.2 or in sodium dodecyl sulfate, by two-dimensional gel electrophoresis and was further confirmed by partial NH2-terminal sequencing. The NH2-terminal amino-acid sequences of fourteen of the components were determined, from 5 to 27 cycles, by automated liquid-phase sequencing. According to the sequence data and predictions of secondary structure, different groups of homologous proteins were established. Based on the presented results, two thionins, one trypsin inhibitor and one alpha-amylase/subtilisin inhibitor are included among the purified proteins. PMID- 24220777 TI - Mass-spectrometric quantitation of cytokinins in tobacco crown-gall tumours induced by mutated octopine Ti plasmids of Agrobacterium tumefaciens. AB - The levels of the major cytokinins, zeatin, zeatin riboside, zeatin riboside-5' monophosphate and zeatin-7-glucoside were measured in tobacco (Nicotiana tabacum L.) crown-gall tissues carrying insertion and deletion mutations in the T-DNA. Measurements were made by combined gas chromatography-mass spectrometry using selected ion monitoring with (15)N- and (2)H-labelled internal standards. The results demonstrate that, relative to wild-type tumour tissue, cytokinin levels are considerably elevated in tissues lacking functional T-DNA auxin-biosynthetic genes. From a detailed analysis of the major cytokinin metabolites it is concluded that a reduction in the extent of cytokinin degradation via N(6)-side chain cleavage is an important factor leading to increased cytokinin levels in these tissues. PMID- 24220778 TI - Induction of a high-capacity nitrate-uptake mechanism in barley roots prompted by nitrate uptake through a constitutive low-capacity mechanism. AB - Roots of nitrate-starved and nitrate-pretreated seedlings of Hordeum vulgare were used to investigate the induction of a high-capacity uptake mechanism for nitrate. When exposed to 0.2 mmol.l(-1)KNO3, nitrate-starved roots took up nitrate at a rate of approx. 1 MUmol.(g FW)(-1).h(-1); K(+) was absorbed at a rate ten-times higher. Nitrate uptake accelerated after a lag of about 1 h, until it matched the rate of K(+) uptake about 4 h later. p-Fluorophenylalanine (FPA), which prevents the synthesis of functioning proteins, suppressed the development of the high-capacity mechanism. Pretreatment of the roots with 0.2 mmol.l(-1) Ca(NO3)2 for 24 h established the high-capacity mechanism. Pretreated roots were able to absorb nitrate at high rates immediately upon exposure to 0.2 mmol.l( 1)KNO3, in the absence or presence of FPA. The high-capacity mechanism, once established, appeared to have a protein turnover as slow as that of the low capacity mechanism or that of the mechanism involved in the uptake of K(+). In contrast, the mechanisms for the transport of nitrate and K(+) into the xylem vessels were completely blocked by FPA within 1 h of application, confirming earlier evidence for a rapid turnover of the transport proteins in the xylem parenchyma.Nitrate reduction proceeded at rates which were roughly one-tenth as large as the rates of the respective nitrate-uptake processes, indicating that nitrate-reductase activity was determined by the rate of nitrate uptake and not vice versa.We conclude that the formation of a high-capacity nitrate-uptake mechanism in barley roots occurs in response to nitrate uptake through a constitutive mechanism of low capacity which appears to function as a sensing mechanism for nitrate in the environment of the roots. PMID- 24220779 TI - Jasmonate-induced alteration of gene expression in barley leaf segments analyzed by in-vivo and in-vitro protein synthesis. AB - Jasmonic-acid methylester promotes barley leaf senescence without changing the average synthesizing capacity for bulk leaf proteins in the treated tissues. This protein balance is the result of a massive formation of jasmonate-induced proteins (JIPs), which cannot be detected in controls (water-treated leaf segments). Jasmonate-induced proteins synthesized in vivo are virtually identical to the respective polypeptides translated in a wheat-germ system if programmed with the RNA of jasmonate-treated leaf segments. Both in-vivo-and in-vitro-formed JIPs correspond with molecular sizes of Mr 110, 66, 30, 23 and 10/12 kilodaltons. This observation indicates little if any post-translational modification. Specific mRNAs for JIPs and the JIPs labeled in vivo can be detected 3-5 h after jasmonate addition. Synthesis of JIPs increases up to 24 h whereas, at the same time, the translatable mRNAs for normal leaf proteins decrease drastically. This massive alteration of gene expression is reminiscent of heat-shock or other stress responses, but the proteins induced by jasmonate differ from those induced by elevated temperature with respect to molecular size, immunological relatedness, and kinetics of synthesis. It is suggested that JIP synthesis is rather a cause than a consequence of the common senescence symptoms and thus could represent some kind of early "stress" response in senescence induced by jasmonic-acid methylester. The action of jasmonic-acid methylester in gene expression points to a control at the transcript level. PMID- 24220780 TI - Cytoplasmic free calcium in Riccia fluitans L. and Zea mays L.: Interaction of Ca(2+) and pH? AB - In cells of Zea mays (root hairs, coleoptiles) and Riccia fluitans (rhizoids, thalli) intracellular Ca(2+) and pH have been measured with double-barrelled microelectrodes. Free Ca(2+) activities of 109-187 nM (Riccia rhizoids), 94-160 nM (Riccia thalli), 145-231 nM (Zea root hairs), 84-143 nM (Zea coleoptiles) were found, and therefore identified as cytoplasmic. In a few cases (Riccia rhizoids), free Ca(2+) was in the lower millimolar range (2.3+/-0.8 mM). A change in external Ca(2+) from 0.1 to 10 mM caused an initial and short transient increase in cytoplasmic free Ca(2+) which finally levelled off at about 0.2 pCa unit below the control, whereas in the presence of cyanide the Ca(2+) activity returned to the control level. It is suggested that this behaviour is indicative of active cellular Ca(2+) regulation, and since it is energy-dependent, may involve a Ca(2+)-ATPase. Acidification of the cytoplasmic pH and alkalinization of the vacuolar pH lead to a simultaneous increase in cytoplasmic free Ca(2+), while alkalinization of pHc decreased the Ca(2+) activity. Since this is true for such remote organisms as Riccia and Zea, it may be concluded that regulation of cytoplasmic pH and free Ca(2+) are interrelated. It is further concluded that double-barrelled microelectrodes are useful tools for investigations of intracellular ion activities in plant cells. PMID- 24220781 TI - Photosynthesis and apparent affinity for dissolved inorganic carbon by cells and chloroplasts of Chlamydomonas reinhardtii grown at high and low CO2 concentrations. AB - Chloroplasts with high rates of photosynthetic O2 evolution (up to 120 MUmol O2. (mg Chl)(-1).h(-1) compared with 130 MUmol O2. (mg Chl)(-1).h(-1) of whole cells) were isolated from Chlamydomonas reinhardtii cells grown in high and low CO2 concentrations using autolysine-digitonin treatment. At 25 degrees C and pH=7.8, no O2 uptake could be observed in the dark by high- and low-CO2 adapted chloroplasts. Light saturation of photosynthetic net oxygen evolution was reached at 800 MUmol photons.m(-2).s(-1) for high- and low-CO2 adapted chloroplasts, a value which was almost identical to that observed for whole cells. Dissolved inorganic carbon (DIC) saturation of photosynthesis was reached between 200-300 MUM for low-CO2 adapted chloroplasts, whereas high-CO2 adapted chloroplasts were not saturated even at 700 MUM DIC. The concentrations of DIC required to reach half-saturated rates of net O2 evolution (Km(DIC)) was 31.1 and 156 MUM DIC for low- and high-CO2 adapted chloroplasts, respectively. These results demonstrate that the CO2 concentration provided during growth influenced the photosynthetic characteristics at the whole cell as well as at the chloroplast level. PMID- 24220782 TI - The oxidation of exogenous NADH by mitochondria of Euglena gracilis. AB - A novel oxidase activity of external NADH was found in mitochondria of a streptomycin-bleached mutant and the wild strain of Euglena gracilis. In contrast to higher plants the oxidation of external NADH in mitochondria of E. gracilis is sensitive to rotenone and yields the same phosphorylation efficiency as the matrix pool of NADH. Simulation of this activity by the classic complex I of the matrix side of the mitochondrial membrane, as a result of preparation-generated artefacts, is excluded. The external NADH-dehydrogenase activity is bound to the inner mitochondrial membrane with its active side facing the cytosol. State-4 enzyme activity is only slightly influenced by pH in the physiological range, whereas state-3 oxidation indicates an optimum in the physiological pH, as expected from a limitation by the ATPase. The external redox potential of NADH does not control enzyme activity. The results are discussed with respect to the metabolic status of the cells at the time of harvesting. PMID- 24220783 TI - Light-dependent, but phytochrome-independent, translational control of the accumulation of the P700 chlorophyll-a protein of photosystem I in barley (Hordeum vulgare L.). AB - This work reports on the regulation of synthesis of the P700 chlorophyll-a apoprotein of photosystem I in barley. The mRNA for the P700 apoprotein is almost exclusively confined to the plastid membrane-bound polysomes. However, the mRNA for the 32-kDa herbicide-binding protein of photosystem II is found in both the soluble and membrane-bound polysomes.The mRNA for the P700 apoprotein is found in similar amounts in dark-grown and light-grown wild-type as well as mutant xantha l(81) barley. The latter mutant is deficient in chlorophyll biosynthesis. However, while wild-type leaves accumulate the P700 chlorophyll-a protein only in the light, mutant leaves never accumulate the P700 apoprotein.A more sensitive approach was taken using isolated plastids to study P700 apoprotein synthesis. Etioplasts did not synthesize detectable P700 apoprotein even when the etioplasts were exposed to light. However, only a 1-min exposure of leaves to light was necessary to induce P700 apoprotein synthesis by isolated plastids.Phytochrome involvement in controlling P700 apoprotein synthesis was tested by using red/farred light treatment of leaves. These treatments showed no far-red reversibility of red-induced P700-apoprotein synthesis in isolated plastids even after 3 h of darkness after the light treatments. From these data we conclude that the accumulation of P700 apopootein is not under the control of phytochrome and that the light induction of P700 apoprotein is most likely mediated through the protochlorophyllide/chlorophyllide system. This control, however, may also involve cytoplasmic signals as the synthesis of the P700 apoprotein is not turned on in illuminated etioplasts. PMID- 24220784 TI - The loci of perception for phytochrome control of internode growth in light-grown mustard: Promotion by low phytochrome photoequilibria in the internode is enhanced by blue light perceived by the leaves. AB - Under continuous white light (WL), extension growth of the first internode in Sinapis alba L. was promoted by low red (R): far-red (FR) ratios reaching the stem and-or the leaves. Conversely, the growth promotion by end-of-day light treatments was only triggered by FR perceived by the leaves and cotyledons, while FR given to the growning internode alone was tatally ineffective. Continuous WL+FR given to the internode was also in-effective if the rest of the shoot remained in darkness. Both the background stem growth, and the growth promotion caused by either an end-of-day FR pulse or continuous WL+FR given to the internode, increased with increasing fluence rates of WL given to the rest of the shoot. The increase by WL of the growth-stimulatory effect of low phytochrome photoequilibria in the internode appears to be mediated by a specific blue-light absorbing photoreceptor, as blue-deficient light from sodium-discharge lamps, or from filtered fluorescent tubes, promoted background stem growth similarly to WL but did not amplify the response to the R:FR ratio in the internode. Supplementing the blue-deficient light (94 MUmol.m(-2).s(-1)) with low fluence rates of blue (<9 MUmol.m(-2).s(-1)) restored the promotive effect of low R:FR reaching the internode. PMID- 24220785 TI - The calmodulin-stimulated ATPase of maize coleoptiles is a 140000-Mr polypeptide. AB - The calmodulin-stimulated ATPase of maize (Zea mays L.) coleoptiles has been purified by calcium-dependent binding to a calmodulin affinity column. In the presence of protease inhibitors (phenylmethylsulfonylfluoride and chymostatin) a polypeptide of relative molecular mass (Mr) 140000 (+/-10000) is obtained on sodium-dodecylsulphate polyacrylamide gels. This polypeptide is recognised specifically by an affinity-purified polyclonal antibody to mammalian calmodulin stimulated calcium-pumping ATPases and is of similar Mr to the erythrocyte membrane calcium pump (138000 Mr). PMID- 24220786 TI - Pubic ramus convexity or ballooning: a sentinel sign for severe periacetabular osteolysis in total hip arthroplasty. AB - Osteolysis is a significant long-term problem in hip arthroplasty. Plain radiographs are the routine investigation of choice for monitoring hip arthroplasty patients; however, the recognition of clinically significant osteolysis can be challenging. We present two case reports of arthroplasty patients with ballooning and expansion of the superior pubic ramus with loss of the normal concavity of the ilio-pectineal line. Both patients subsequently displayed massive pubic osteolysis at the time of revision surgery. We suggest that the presence of convexity of the ilio-pectineal line/superior pubic ramus indicates established pelvic osteolysis. PMID- 24220787 TI - An editor's journey: 6 years with European Radiology. AB - Recent changes in the journal European Radiology and the development of our sister journal Insights into Imaging are discussed. So too are problems related to redundant publications and assessments of quality. In particular, it must be realised that the Impact Factor of a journal is not the only parameter of success. PMID- 24220788 TI - [Precipitation of piritramide and cefazolin. Study of the dependence on concentration and pH]. AB - BACKGROUND: Drug incompatibility might lead to precipitation with subsequent serious complications, such as transient pulmonary embolism. Recently, incompatibility of the opioid piritramide with cephalosporin antibiotics was described. As both drugs are frequently administered in a perioperative setting, the present study addressed the question whether the precipitation effect depends on the piritramide concentration or on the pH of the solution. Moreover, it was tested whether the precipitate reversibly dissolves in a physiological saline solution. METHODS: Piritramide was diluted to the final test concentrations in 0.9 % sodium chloride solution. Precipitation tests were performed by combining 1 ml of the respective piritramide dilution with 1 ml of cefazolin (20 mg/ml) in a syringe. Precipitation was detected by visual inspection as an opaque whitish appearance of the mixture. Each concentration was tested 5 times. The pH values of the tested piritramide concentrations were determined using a 3-point calibrated pH meter. The precipitate formed in 1 ml of cefazolin (20 mg/ml) and 1 ml of piritramide (5 mg/ml) was diluted in 3 ml physiological saline. RESULTS: The piritramide concentrations 5 mg/ml, 3.75 mg/ml and 3 mg/ml precipitated in the presence of cefazolin (20 mg/ml), while the concentrations 1.875 mg/ml, 1 mg/ml and 0.5 mg/ml did not produce a precipitate. To exclude the possibility that changes in pH of the tested dilutions might be responsible for these findings, the pH values of the piritramide dilutions were measured. The mean pH values of the concentrations 5 mg/ml, 3.75 mg/ml, 3 mg/ml, 1.875 mg/ml and 1 mg/ml did not differ significantly (pH 3.89 +/- 0.004, n = 26, tested by ANOVA). However, the mean pH of 0.5 mg/ml was significantly different from the other tested dilutions (pH 3.98 +/- 0.02, n = 6; p < 0.01 by ANOVA). After diluting the precipitate of piritramide and cefazolin in physiological saline the whitish precipitate completely dissolved and the resulting solution became clear (n = 5). CONCLUSION: The results imply a concentration dependence of the precipitation with cefazolin, while a correlation with pH changes could not be detected. In cases of co-administration of cephalosporins and piritramide, a piritramide concentration of 1 mg/ml seems to be safe and does not form a precipitate. As the precipitate could be reversed by diluting in saline solution it is most likely that a proton switch between the carboxylic acid moiety of cefazolin and the amino group of piritramide causes the precipitation. PMID- 24220789 TI - [Hydroxyethyl starch]. PMID- 24220791 TI - Function of aspartic acid residues in optimum pH control of L-arabinose isomerase from Lactobacillus fermentum. AB - L-Arabinose isomerase (L-AI) catalyzes the isomerization of L-arabinose to L ribulose and D-galactose to D-tagatose. Most reported L-AIs exhibit neutral or alkaline optimum pH, which is less beneficial than acidophilic ones in industrial D-tagatose production. Lactobacillus fermentum L-AI (LFAI) is a thermostable enzyme that can achieve a high conversion rate for D-galactose isomerization. However, its biocatalytic activity at acidic conditions can still be further improved. In this study, we report the single- and multiple-site mutagenesis on LFAI targeting three aspartic acid residues (D268, D269, and D299). Some of the lysine mutants, especially D268K/D269K/D299K, exhibited significant optimum pH shifts (from 6.5 to 5.0) and enhancement of pH stability (half-life time increased from 30 to 62 h at pH 6.0), which are more favorable for industrial applications. With the addition of borate, D-galactose was isomerized into D tagatose by D268K/D269K/D299K at pH 5.0, resulting in a high conversion rate of 62 %. Based on the obtained 3.2-A crystal structure of LFAI, the three aspartic acid residues were found to be distant from the active site and possibly did not participate in substrate catalysis. However, they were proven to possess similar optimum pH control ability in other L-AI, such as that derived from Escherichia coli. This study sheds light on the essential residues of L-AIs that can be modified for desired optimum pH and better pH stability, which are useful in D tagatose bioproduction. PMID- 24220793 TI - Humus-reducing microorganisms and their valuable contribution in environmental processes. AB - Humus constitutes a very abundant class of organic compounds that are chemically heterogeneous and widely distributed in terrestrial and aquatic environments. Evidence accumulated during the last decades indicating that humic substances play relevant roles on the transport, fate, and redox conversion of organic and inorganic compounds both in chemically and microbially driven reactions. The present review underlines the contribution of humus-reducing microorganisms in relevant environmental processes such as biodegradation of recalcitrant pollutants and mitigation of greenhouse gases emission in anoxic ecosystems, redox conversion of industrial contaminants in anaerobic wastewater treatment systems, and on the microbial production of nanocatalysts and alternative energy sources. PMID- 24220792 TI - Engineering of the TetR family transcriptional regulator SAV151 and its target genes increases avermectin production in Streptomyces avermitilis. AB - Avermectins produced by Streptomyces avermitilis are used commercially for broad spectrum parasite control in medical, veterinary, and agricultural fields. Our previous comparative transcriptome analysis of wild-type strain ATCC31267 vs. avermectin-overproducing strain 76-02-e revealed that the gene SAV151, which encodes a TetR family transcriptional regulator, was downregulated in 76-02-e. In the present study, we investigated the role of SAV151 in avermectin production. Deletion of SAV151 increased avermectin yield ~1-fold in ATCC31267, and this phenotype was complemented by a single copy of SAV151. Overexpression of SAV151 in ATCC31267 reduced avermectin yield by ~70%. RT-PCR analysis showed that the promoting effect of SAV151 deletion on avermectin production was not due to alteration of ave genes at the transcriptional level. SAV151 negatively regulated the transcription of itself and of the adjacent transcriptional unit SAV152 SAV153-SAV154. In chromatin immunoprecipitation and gel shift assays, purified His6-tagged SAV151 protein bound to the bidirectional SAV151-SAV152 promoter region. SAV151 bound to two palindromic sequences in this region and thereby repressed transcription from both directions. Two of the SAV151 target genes, SAV152 (which encodes a putative dehydrogenase) and SAV154 (which encodes a putative hydrolase), had promoting effects on avermectin production. Our findings provide the basis for a strategy to increase avermectin production by controlling SAV151 and its target genes. PMID- 24220794 TI - Movement initiation in groups of feral horses. AB - Herds of ungulates, flocks of birds, swarms of insects and schools of fish move in coordinated groups. Computer models show that only one or very few animals are needed to initiate and direct movement. To investigate initiation mechanisms further, we studied two ways in which movement can be initiated in feral horses: herding, and departure from the group. We examined traits affecting the likelihood of a horse initiating movement i.e. social rank, affiliative relationships, spatial position, and social network. We also investigated whether group members join a movement in dominance rank order. Our results show that whereas herding is exclusive to alpha males, any group member may initiate movement by departure. Social bonds, the number of animals interacted with, and the spatial position were not significantly associated with movement initiation. We did not find movement initiation by departure to be exclusive to any type of individual. Instead we find evidence for a limited form of distributed leadership, with higher ranking animals being followed more often. PMID- 24220795 TI - The energy-maintenance strategy of goitered gazelles Gazella subgutturosa during rut. AB - In many polygynous ruminant species, males decrease their food intake considerably during the rut. To explain this phenomenon of rut-reduced hypophagia, two main hypotheses, the Foraging-Constraint Hypothesis and Energy Saving Hypothesis, have been proposed. In our research, we assessed the behavioral strategy of goitered gazelles (Gazella subgutturosa) through the rutting period. According to our findings, male goitered gazelles spent less time feeding during the rut compared to pre- and post-rut feeding times, but then maximized their energy intake during the rutting season when they were not engaged in rut-related behaviors. Females, in contrast, did not change their time budgets across the different stages of the rut. Therefore, rut-induced hypophagia is mainly arising from the constraints of rut-related behaviors for male goitered gazelles, so that the Foraging-Constraint Hypothesis better explains their strategy during rut. PMID- 24220790 TI - Linking seasonal inorganic nitrogen shift to the dynamics of microbial communities in the Chesapeake Bay. AB - Seasonal shifts of dissolved inorganic nitrogen (DIN) and the dynamics of microbial communities for nitrogen transformation were investigated in the water column of Chesapeake Bay. The relative abundance of nitrogen over phosphorus (N) showed a strong seasonal and spatial pattern: gradually decreased from upstream to downstream; high in winter and low in summer. Because the phosphorus concentration remained relatively stable, the spatiotemporal pattern of N implied that a substantial fraction of DIN was removed in the bay, especially in summer. Correlation analyses indicated the functional microbial communities and environmental variables, such as temperature, dissolved oxygen, salinity, played important roles for connecting the seasonal variation of N. Among them, temperature was the trigger factor. High temperature in the summer induced the growth of functional microbes, which subsequently consumed a large portion of DIN inputted from the tributaries and reduced the N. The current study provided the relative importance of microbial communities and environmental variables in driving the DIN loss in the bay. PMID- 24220796 TI - Development of observational learning during school formation in jack mackerel Trachurus japonicus juveniles. AB - We assessed whether the development of observational learning in jack mackerel Trachurus japonicus juveniles corresponds with that of their schooling behaviour. Schooling behaviour was quantitatively analyzed by nearest neighbour distance and separation angle in two size classes of fish, 20-mm and 40-mm in body length. Observer and non-observer fish with matching sizes were conditioned to pellets by temporarily stopping aeration. Observer fish were provided with five observation trials of other individuals feeding near an air stone when aeration was stopped. After the observation trial, fish were conditioned to pellets with the stop of aeration, and then the learning process was evaluated by the increase in the association with the feeding area when aeration was stopped. In 20-mm fish, which were at an immature stage of schooling behaviour, there was no difference in the learning process between observer and non-observer fish. In contrast, 40-mm fish were confirmed to have a well-developed schooling behaviour, and the observer learnt the feeding area more efficiently than the non-observer. This study provides evidence that observational learning develops along with the development of the social interaction. PMID- 24220797 TI - Why do cervids feed on aquatic vegetation? AB - Consumption of aquatic plants is rare among cervids, despite the common occurrence of this form of vegetation. However, the paucity of literature reporting on this feeding behaviour suggests that Na (but also other minerals), protein, and the ubiquitous availability of aquatic vegetation may play a role in its consumption. We present results quantifying those factors that regulate the consumption of aquatic plants in the Iberian red deer. We focussed our study primarily on two questions: (i) what nutritional values are red deer seeking in the aquatic plants?; and (ii) why do red deer primarily use aquatic plants during the summer? A comparison of the seasonal variations in Na content between terrestrial vs. aquatic vegetation did not fully support the hypothesis that aquatic plants are being consumed more in summer because of any seasonal variation in Na availability. The Na content in the aquatic vegetation was adequate all the year-round; whereas, the Na content in the terrestrial vegetation was consistently deficient. However, a greater summer content of essential minerals and protein in the aquatic vegetation may be the cause for their consumption exclusively during the summer. We suggest that seasonal variations in the consumption of aquatic vegetation by cervids is primarily driven by temporal variations in the nutrient content, combined with seasonal variations in the physiological demands for these nutrients. PMID- 24220798 TI - Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis. AB - The aim of the present study was to determine whether BCL6 is expressed during malignant transformation of the large bowel and to assess whether, and to what extent, immunoreactivity is related to the different stages of neoplastic progression. Samples of normal colorectal mucosa (n=22), microadenomas (n=22) and colorectal cancer (n=22), were analyzed by immunohistochemistry, immunofluorescence coupled with confocal microscopy and western blotting. Our results clearly outlined the marked increase occurring in both intensity and density of BCL6 protein expression in the normal mucosa-microadenoma-carcinoma sequence. Immunohistochemistry and immunofluorescence analyses showed that BCL6 is expressed at low levels in normal mucosa and increases in microadenoma and in cancer with statistical significance. These results were confirmed by western blotting data. The increasing expression of BCL6 in human colorectal cancer development suggests the involvement of BCL6 in tumor progression, from the earliest stages of carcinogenesis with significant increase in cancer. The enhanced understanding of the biological role of BCL6, previously shown to exert a key role in lymphomagenesis, may lead to a re-evaluation of this protein and may highlight the importance of performing further studies in order to identify novel therapeutic targets for colorectal cancer. PMID- 24220799 TI - Caspase inhibition via A3 adenosine receptors: a new cardioprotective mechanism against myocardial infarction. AB - PURPOSE: 2-CL-IB-MECA, (A3 adenosine receptor agonist)(A3AR) mediated cardioprotection is well documented although the associated intracellular signalling pathways remain unclear. Here we demonstrate a role of the pro survival signalling pathways MEK1/2-ERK1/2 and PI3K/AKT and their effect on modifying Caspase-3 activity in A3AR mediated cardioprotection. METHODS: Isolated perfused rat hearts or primary adult rat cardiac myocytes were subjected to ischaemia/hypoxia and reperfusion/reoxygenation, respectively. 2-CL-IB-MECA (1 nM) was administered at the onset of reperfusion/reoxygenation in the presence and absence of either the PI3K inhibitor Wortmannin (5 nM) or MEK1/2 inhibitor UO126 (10 MUM). Heart tissues were harvested for assessment of p ERK1/2(Thr202/Tyr204) or p-AKT (Ser-473) status or underwent infarct size assessment. Cardiac myocytes underwent flow-cytometric analysis for apoptosis, necrosis, cleaved-caspase 3/p-BAD (Ser-112 and Ser-136) activity post reoxygenation. RESULTS: 2-CL-IB-MECA significantly reduced infarct size compared to non-treated controls, where co-administration with either of the kinase inhibitors abolished the infarct sparing effects. Administration of 2-CL-IB-MECA at reperfusion significantly upregulated the status of p-ERK1/2 and p-AKT compared to time matched controls in a UO126 and Wortmannin sensitive manner respectively. 2-CL-IB-MECA when administered throughout reoxygenation significantly reduced apoptosis, necrosis, cleaved-caspase 3 activity and increased p-BAD (Ser-112) and p-BAD (Ser-136) activity in myocytes subjected to hypoxia/reoxygenation injury. The cytoprotective effect was abolished by co administration with the kinase inhibitors Wortmannin and/or UO126. CONCLUSIONS: We have described the molecular mechanisms associated with A3AR mediated cardioprotection indicating a role for the pro-survival signalling pathways that decrease caspase-3 activity. These observations provide novel insight into the pharmacological effects of A3ARs in ameliorating myocardial ischaemia/reperfusion injury. PMID- 24220800 TI - The NLRP3 inflammasome and diabetic cardiomyopathy : editorial to: "Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model" by Beibei Luo et al. PMID- 24220801 TI - Longitudinal assessments of quality of life and late toxicities before and after definitive chemoradiation for esophageal cancer. AB - OBJECTIVE: Definitive chemoradiotherapy is often considered for locally advanced esophageal cancer. We studied the effect of chemoradiotherapy treatment on patients' quality of life and late toxicities. METHODS: Patients undergoing definitive 5-fluorouracil and cis-diammine-glycolatoplatinum (nedaplatin) therapy concurrent with radiotherapy for esophageal cancer without operation adaptation completed standardized quality-of-life questionnaires before and after chemoradiotherapy and at regular times up to ~5 years. We analyzed differences in a generic quality-of-life score questionnaire (Functional Assessment of Cancer Therapy-Esophageal scoring) over time by using a linear mixed-effects model. RESULTS: Longitudinal changes before the start of treatment were able to be evaluated in a total of 80 patients. The quality-of-life score before treatment was worse in patients with advanced stages than those with early stages. The quality-of-life score deteriorated once at the time of 2 or 3 months after starting chemoradiotherapy compared with pre-chemoradiotherapy and recovered and rose higher at 4 or 5 months than before starting chemoradiotherapy. After that, the recovery of quality of life was maintained up to the observation end. The score of physical functioning such as fatigue, nausea/vomiting, pain and dyspnea deteriorated at the time of 2 or 3 months after starting chemoradiotherapy compared with before chemoradiotherapy (80, 86, 94 and 89%). CONCLUSIONS: The quality-of-life score deteriorates once from before treatment due to acute complications by chemoradiotherapy, but recovers at 4 or 5 months and becomes better than before treatment. PMID- 24220802 TI - Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction. AB - OBJECTIVE: Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. METHODS: The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. RESULTS: Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non Barrett's adenocarcinoma with gastritis patients 'and younger age in non Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. CONCLUSIONS: This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including Barrett's esophagus-related, positive gastritis-related, and Barrett's esophagus and gastritis-unrelated adenocarcinoma of the esophagogastric junction. PMID- 24220803 TI - Denaturing gradient gel electrophoresis identifies genomic DNA polymorphism with high frequency in maize. AB - We have used denaturing gradient gel electrophoresis (DGGE) to identify genomic DNA polymorphism in maize (Zea mays L.). DGGE probes detect polymorphism in maize at a frequency comparable to the incidence of restriction fragment length polymorphism (RFLP). Probes identifying polymorphism were mapped to maize chromosome arms by utilizing DGGE and maize lines carrying B-A chromosomal translocations. The methods for library construction, probe screening, and genome analysis, described here for maize, can also be applied to the genomic analysis of other organisms. PMID- 24220804 TI - Relationships between genotype x environment interaction and genetic correlation of the same trait measured in different environments. AB - Relationships between genotype x environment interaction and genetic correlation of the same trait measured in different fixed environments are derived by comparing the variance-covariance structures of observations between a one-way multiple-trait linear model and a two-way single-trait mixed linear model. In the latter model, heterogeneity of interaction variances among environments and non zero covariances among interactions are assumed, in addition to the heterogeneity of error variances and non-zero covariances between genetic-group effects and interactions that were accommodated in earlier work. The results are applicable to more than two environments and to unbalanced data. This paper is a generalization and a correction of earlier works. PMID- 24220805 TI - Fertile progeny of a hybridization between soybean [Glycine max (L.) Merr.] and G. tomentella Hayata. AB - A colchicine-doubled F1 hybrid (2n=118) of a cross between PI 360841 (Glycine max) (2n=40) x PI 378708 (G. tomentella) (2n=78), propagated by shoot cuttings since January 1984, produced approximately 100 F2 seed during October 1988. One fourth of the F2 plants or their F3 progeny have been analyzed for chromosome number, pollen viability, pubescence tip morphology, seed coat color, and isoenzyme variation. Without exception, all plants evaluated possessed the chromosome number of the G. max parent (2n=40). Most F2 plants demonstrated a high level of fertility, although 2 of 24 plants had low pollen viability and had large numbers of fleshy pods. One F2 plant possessed sharp pubescence tip morphology, whereas all others were blunt-tipped. All evaluated F2 and F3 plants expressed the malate dehydrogenase and diaphorase isoenzyme patterns of the G. max parent and the endopeptidase isoenzyme pattern of the G. tomentella parent. Mobility variants were observed among progeny for the isoenzymes phosphoglucomutase, aconitase, and phosphoglucoisomerase. This study suggests that the G. Tomentella chromosome complement has been eliminated after genetic exchange and/or modification has taken place between the genomes. PMID- 24220806 TI - Hordeum chilense repetitive sequences. Genome characterization using biotinylated probes. AB - A library of random DNA fragment clones of wild barley Hordeum chilense was screened for clones of repeated nucleotide sequences. Five clones were isolated that gave a stronger hybridization signal in colony and dot blot hybridization with total H. chilense DNA in comparison to Triticum aestivum DNA. Clones labelled with biotinylated nucleotides were used as probes to investigate the repeated sequences organization in the H. chilense genome. Tandemly arranged and interspersed sequences have been found, together with homology differences with related sequences present in T. Aestivum, which could allow the differentiation of H. chilense DNA when it is present in wheat. We show that biotin can replace the use of (32)P in preparing repeated sequence probes for Southern and DNA dot blot analyses. PMID- 24220807 TI - The Rj4 allele in soybean represses nodulation by chlorosis-inducing bradyrhizobia classified as DNA homology group II by antibiotic resistance profiles. AB - To determine the relationship between nodulation restriction by the Rj4 allele of soybean, rhizobitoxine-induced chlorosis, and taxonomic grouping of bradyrhizobia, 119 bradyrhizobial isolates were tested in Leonard jar culture for nodulation response and chlorosis induction. In addition to strain USDA 61, the strain originally reported as defining the Rj4 response, eight other isolates (i.e., USDA 62, 83, 94, 238, 252, 259, 260, and 340) were discovered to elicit the nodulation interdiction of the Rj4 allele. Only 16% of all the bradyrhizobial strains tested induced chlorosis, but seven of the nine strains (78%) interdicted by the Rj4 allele were chlorosis-inducing strains. Furthermore, in tests for antibiotic resistance profile, eight of the nine interdicted strains (89%) were classed in DNA homology group II. This evidence suggests that the Rj4 allele has a positive value to the host plant in shielding it from nodulation by certain chlorosis-inducing bradyrhizobia of a DNA homology group with impaired efficiency of nitrogen fixation with soybean. PMID- 24220808 TI - Intergeneric (intersubtribe) hybridization between Moricandia arvensis and Brassica A and B genome species by ovary culture. AB - Intergeneric hybrids between Moricandia arvensis (C3-C4 intermediate species) and Brassica A and B genome species (B. campestris and B. nigra) were produced via ovary culture. When M. arvensis was used as a female parent, the hybrid embryo yield (0.25-0.45 embryo per pollination) was similar between two genomes, regardless of the male parent. The reciprocal hybrid using B. campestris as a female was also obtained, although yield of embryo was lower (0.02 embryo per pollination). On the other hand, no hybrids were obtained without the in vitro technique. As most hybrid embryos could not develop normal shoots, plants were regenerated by inducing shoots on the cultured hypocotyl. The hybrid nature of the regenerated plant was confirmed morphologically and cytogenetically. A certain amount of bivalents (2.52-2.71) in the hybrids indicated the existence of partial chromosome homology between two genera. The present results indicate that ovary culture is an effective technique for overcoming the crossing barrier between M. arvensis and Brassica cultivated species. PMID- 24220809 TI - Molecular cloning and chromosomal location of genes encoding the "Early methionine-labelled" (Em) polypeptide of Triticum aestivum L. var. Chinese Spring. AB - The "Early-methionine-labelled" (Em) polypeptide is the most abundant cytosolic polypeptide found in mature wheat embryos. Using a near full-length cDNA clone as a hybridisation probe to detect genomic sequences by Southern blotting of electrophoretic separations of genomic DNA derived from Triticum aestivum L. var. Chinese Spring and a series of its aneuploid derivatives, we demonstrate that the Em polypeptide is the product of a small multigene family in which the copies are located on each of the long arms of the homoeologous group 1 chromosomes. Screening of a variety of genotypes additionally reveals a number of restriction fragment length polymorphisms associated with these loci. Screening of a library of genomic DNA cloned in the vector lambdaEMBL 4 has resulted in the isolation of a genomic fragment containing two closely linked Em genes. These are separated by ca. 2.5 kb. Analysis of restriction enzyme digests of this clones fragment has identified it as originating from chromosome 1A. PMID- 24220810 TI - Genetic relatedness in open-pollinated families of two leguminous tree species, Robinia pseudoacacia L. and Gleditsia triacanthos L. AB - When conducting tree breeding experiments, geneticists often assume that individuals from open-pollinated families are halfsibs. The reliability of this assumption was tested using data from enzyme electrophoresis to estimate the genetic relatedness among progeny within 22 open-pollinated families of Robinia pseudoacacia L. (black locust) and 34 open-pollinated families of Gleditsia triacanthos L. (honey locust) from natural stands. An algorithm employing population estimates of fixation indices, pollen allele frequencies, and selfing rates was used to calculate the mean expected number of alleles in common across loci under assumptions of either full-sib (i.e., a single pollen parent) or half sib (i.e., random mating) relationships. For each open-pollinated family, the average coefficient of relationship among progeny was calculated by linear interpolation from the observed number of alleles in common. For most families of both species, coefficients were significantly higher than 0.25 (half-sib relation), but were significantly lower than 0.50 (full-sib relation). These results suggest that the assumption of a half-sib relationship among progeny of open-pollinated families is violated for these tree species. More critical to the estimation of heritabilities and the prediction of genetic gains was the observation that estimates of the coefficient of relationship varied widely among open-pollinated families (for R. pseudoacacia r 0=0.20-0.43, mean=0.34; for G. triacanthos r 0=0.29-0.55, mean=0.36). PMID- 24220811 TI - Linkage arrangement of restriction fragment length polymorphism loci in Brassica oleracea. AB - A detailed genetic linkage map of Brassica oleracea was constructed based on the segregation of 258 restriction fragment length polymorphism loci in a broccoli * cabbage F2 population. The genetic markers defined nine linkage groups, covering 820 recombination units. A majority of the informative genomic DNA probes hybridized to more than two restriction fragments in the F2 population. "Duplicate" sequences having restriction fragment length polymorphism were generally found to be unlinked for any given probe. Many of these duplicated loci were clustered non-randomly on certain pairs of linkage groups, and conservation of the relative linkage arrangement of the loci between linkage groups was observed. While these data support previous cytological evidence for the existence of duplicated regions and the evolution of B. oleracea from a lower chromosome number progenitor, no evidence was provided for the current existence of blocks of homoeology spanning entire pairs of linkage groups. The arrangement of the analyzed duplicated loci suggests that a fairly high degree of genetic rearrangement has occurred in the evolution of B. oleracea. Several probes used in this study were useful in detecting rearrangements between the B. oleracea accessions used as parents, indicating that genetic rearrangements have occurred in the relatively recent evolution of this species. PMID- 24220812 TI - Two-step one-dimensional SDS-PAGE analysis of LMW subunits of glutelin : 1. Variation and genetic control of the subunits in hexaploid wheats. AB - A collection of 222 hexaploid wheat cultivars (including the 207 cultivars studied by Gupta and Shepherd in 1988) from 32 countries was analyzed for variation in the banding patterns of LMW subunits of glutenin using a modified two-step 1-D SDS-PAGE. Seventy percent ethanol at high temperature (>=50 degrees C) was used to selectively dissolve the native glutenins containing A, B, and C subunits and not the albumins and globulins (non-prolamins). This procedure allowed the glutenin subunits A, B and C to be separated in a background free of albumins and globulins, which normally overlap the B and C subunits (LMW subunits of glutenin). Although 40 different B and C subunits were detected, except where the cultivars carried a 1BL-1RS translocation or 1B/1R substitution, each cultivar exhibited from 7 to 16 subunits. These subunits could be divided into 20 band patterns which fell into three groups on the basis of their mutual exclusiveness, with 6, 9, and 5 patterns. Analysis of substitution lines revealed that the different patterns in these groups are controlled by genes on chromosomes 1A, 1B, and 1D, respectively. The least number of subunits was controlled by chromosome 1A and approximately 40% of the cultivars did not contain any band controlled by this chromosome. Thirteen of the cultivars were found to consist of two biotypes with respect to LMW subunits of glutenin. The genetic, evolutionary, and technological implications of these findings are discussed. PMID- 24220813 TI - Genetic evaluation with autosomal and X-chromosomal inheritance. AB - At present, genetic evaluation in livestock using best linear unbiased prediction (BLUP) assumes autosomal inheritance. There is evidence, however, of X chromosomal inheritance for some traits of economic importance. BLUP can accommodate models that include X-chromosomal in addition to autosomal inheritance. To obtain BLUP with autosomal and X-chromosomal additive inheritance for a population in which allelic frequency is equal in the sexes, and that is in gametic equilibrium, we write y i = x'ibeta + ai + si + ei, where y i is the phenotypic value for individual i, x'i, is a vector of constants relating y i to fixed effects, beta is a vector of fixed effects, a i is the additive genetic effect for autosomal loci, S i is the additive genetic effect for X-chromosomal loci, and e i is random error. The covariance matrix of a i's is Asigma A (2) , where A is the matrix of twice the co-ancestries between relatives for autosomal loci, and sigma A (2) is the variance of additive genetic effects for autosomal loci. The covariance matrix of s i's is Ssigma F (2) , where S is a matrix of functions of co-ancestries between relatives for X-chromosomal loci and sigma F (2) is the variance of additive genetic effects for X-chromosomal loci for noninbred females. Given the covariance matrices of random effects a i, si, and e i, BLUPs of autosomal and of X-chromosomal additive effects can be obtained using mixed model equations. Recursive rules to construct S and an efficient algorithm to compute its inverse are given. PMID- 24220814 TI - Mitochondrial DNA variation in long-term tissue cultured rice lines. AB - The effects of long-term tissue culture on mitochondrial DNAs were examined using rice (Oryza sativa) cell suspension cultures. Mitochondrial DNAs were isolated from P. I. 353705 (an indica subspecies of rice similar to 'Asam 5'), its anther culture-derived line BL2 (an 8-year-old cell suspension culture), and five other cell lines (A1, A7, A11, A13, and A23), also derived from BL2 and independently selected for resistance to the lysine analog, S-(2-amino)-ethyl-L-cysteine. Mitochondrial DNAs of the rice lines were digested with ten restriction endonucleases (BamHI, BglII, EcoRI, EcoRV, HindIII, PstI, PvuII, SalI, SmaI, and XhoI), electrophoresed, and transferred to nylon membranes. Southern blots were hybridized with one rice and five maize probes containing mitochondrial genes. The restriction patterns of ten Southern blots and hybridization patterns of 60 endonuclease/probe combinations were analyzed. DNAs from all sources produced unique restriction patterns when digested with HindIII or BglII; with the other endonucleases an array of similarities and differences was observed. Lines BL2 and A11 showed unique patterns with all restriction endonucleases tested. No hybridization pattern differences were observed among the lines when probes containing apt9 and atpA were used. However, extensive hybridization pattern differences were observed with coxI, coxII, rrn18-rrn5, and atp6 probes. Both restriction and hybridization patterns revealed variation due to tissue culture effect. Coxll was most efficient in revealing the uniqueness of BL2. Among the analog selected lines A11 was most divergent, and probes rrn18-rrn5 and atp6 were most efficient in revealing its distinctiveness. Unique mitochondrial genomic organizations were found to be associated with long-term tissue culture. PMID- 24220815 TI - Genetic mapping of isozyme loci in Secale cereale L. AB - The genetics and linkage relationships of several isozymatic and morphological markers have been investigated in different cultivars of rye (Secale cereale L.). The inheritance and the variability among cultivars of three new isozymatic zones are described: GOT2 and LAP, each of them under the control of a two-allele single locus, namely Got2 and Lap, respectively; and 6PGD1 controlled by two loci, 6Pgd1a and 6Pgd1b, which have alleles in common. Four linkage groups have been found: Acp2-Acp3, Got3-Mdh2-Lper4, Mdh1-6Pgd2-Pgi2, and Pgm-Eper2-[Eper1 Eper3]. The assignment of these four groups to the chromosomes 7R, 3R, 1R, and 4R is discussed. PMID- 24220816 TI - Insect-resistant plants with improved horticultural traits from interspecific potato hybrids grown in vitro. AB - Plants were regenerated from petiole calli of interspecific hybrids of Solanum tuberosum x S. berthaultii, an insect-resistant wild species. Callus culture was used to generate genetic changes to overcome the restricted recombination between the two genomes. Two plants out of 58 (3.5%) from calli of hybrid J114-1 showed stable and heritable differences from the hybrid over two cycles of evaluations in the field. Replicated trials were conducted in 1987 and 1988, using two populations of plants propagated by nodal cuttings from the original regenerates maintained in vitro. One regenerate showed insect resistance and increased marketable yield (approximately two fold) in the field. The other had higher levels of phenolic exudate in one of the two types of foliar trichomes associated with the insect resistance mechanism. Some desirable changes were discernible only in sexual progeny of regenerates, not in the regenerates themselves. In a backcross to S. tuberosum, 7 of 14 (50%) regenerates from hybrid F743-4 showed more progeny (up to 15-fold) with improved trichome traits and horticultural characteristics than the original hybrid. The variations were not associated with changes in ploidy. Fifteen plants obtained from these crosses are currently being incorporated into breeding lines. These results suggest that a period of callus culture followed by plant regeneration may aid in the introgression of desirable traits from wild species into crop plants. PMID- 24220817 TI - An alternative statistic for identifying lines useful for improving parents of an elite single cross. AB - Theory and methods for identifying inbred lines (I w) with favorable dominant alleles not present in an elite single cross (I 1*I 2) have been developed recently. Selected I w lines can be crossed to I 1 or to I 2 to transfer new favorable alleles to the single cross. However, favorable alleles already present in the single cross may be lost during selection. It is important to consider both potential gain of favorable alleles from I w and loss of favorable alleles already present in I 1*I 2. The "net improvement" statistic (NI)=maximum [(I 1*I w-I 1xI 2)/2, (I 2*I w-I 1*I 2)/2] estimates the number of loci where favorable alleles can be gained minus the number of loci where favorable alleles can be lost in the single cross. Because I 1*I 2 is constant in an experiment, the method reduces to choosing I w lines with the best mean performance in combination with either I 1 or I 1. NI was compared to estimators previously proposed for identifying lines, namely: (1) minimally biased estimates (MUG') of favorable dominant alleles present in I w but not in I 1 and I 2; (2) minimum estimate of an upper bound (UBND) on MUG; and (3) predicted three-way cross (PTC) performance. Based on a set of maize (Zea mays L.) grain yield data, correlations among the four estimators were relatively high, but indicated that rankings of I w lines vary with the particular estimator used. Rankings of three I w lines based on the frequency of F2 test crosses superior to B73*Mo17 were identical to rankings based on NI, but differed from rankings based on MUG', PTC, and UBND. NI also was the best predictor of the mean of the upper 10% ({ovx}0.1) of (I 2*I w) F2*I 1 or (I 1*I w) F2*I 2 test crosses based on simulated data. Being a simple statistic highly correlated to {ovx}0.1, NI may be useful in applied breeding programs. PMID- 24220818 TI - The use of ecogeographical data in the exploitation of variation from gene banks. AB - As the variation of species is known to be influenced both by ecological and geographical factors, data on the origin of a sample from a given species could be used to infer some of its genetic characteristics. This concept was examined in the context of gene banks, where the assembled diversity usually represents a large range of environments and geographic locations. Results suggest that, although ecological variables in the site of origin can be useful in predicting genetic characteristics in the samples, the use of such data is neither simple nor precise. On the other hand simple geographic data, irrespective of their ecological content, were found to offer an effective method of stratifying and sampling variation in germ plasm collections. PMID- 24220819 TI - Antigenic relationships between petunia peroxidase a and specific peroxidase isoenzymes in other Solanaceae. AB - A highly specific rabbit antiserum raised against peroxidase (PRXa) from petunia (Petunia hybrida) was used to investigate the antigenic relatedness of peroxidases in the Solanaceae. After SDS-PAGE of crude leaf extracts from a large number of species of this family, immunoblotting revealed that cross-reacting protein bands were present in all species tested. In order to determine whether these protein bands represent peroxidases, the peroxidase isoenzymes in thorn apple (Datura stramonium L.), tobacco (Nicotiana tabacum L.), sweet pepper (Capsicum annuum L.), potato (Solanum tuberosum L.), and tomato (Lycopersicon esculentum Mill.) were further analyzed. Immunoblots obtained after native PAGE revealed that the antiserum only recognized fast-moving peroxidase isoenzymes that are localized in the apoplast. Despite their serological relatedness, these peroxidases differed with respect to heat stability and apparent molecular weight. Differences in avidity for the petunia PRXa antiserum were suggested by immunoprecipitation with antibodies bound to protein A-Sepharose. The antiserum did not react with peroxidases from horseradish (Armoracea rusticana Gaertn., Mey and Scherb), turnip (Brassica napus L.), African marigold (Tagetes cresta L.), maize (Zea mays L.), and oats (Avena sativa L.). Apparently, the Solanaceae contain orthologous genes encoding the fast-moving anionic peroxidases homologous to petunia PRXa. PMID- 24220820 TI - Worldwide pattern of multilocus structure in barley determined by discrete log linear multivariate analyses. AB - Data from the electrophoretic assay for seven enzyme loci of 1,032 accessions of cultivated barley, Hordeum vulgare L., from the USDA world barley collection were analyzed for multilocus structure using discrete log-linear multivariate techniques. Three major steps were involved in the analysis: (i) identification and elimination of terms that have inconsequential effects in multilocus association; (ii) construction of a log-linear model that best describes the complete multilocus structure of the genetic system; and (iii) evaluation of each of the association terms included in the model. The results of analyses of two subsets of loci show that the multilocus genetic system of cultivated barley, including loci located on different chromosomes, is organized into hierarchically structured complexes of loci. Multilocus structure differs in various geographical regions of the world. The structure of barleys from Southwest Asia, the putative center of origin for cultivated barley, is intermediate for both subsets of loci. Differences increased progressively across the Eurasian-African landmasses in each direction with increasing distance from Southwest Asia, with the consequence that the barleys from West Europe, East Asia, and Ethiopia are maximally different from those of Southwest Asia and Middle South Asia. PMID- 24220821 TI - Phylogenetic relationships among species of Prunus as inferred by isozyme markers. AB - An isozyme survey of 34 species of Prunus representing subgenera Prunus, Amygdalus, Cerasus, and Lithocerasus detected 110 presumptive alleles at 11 isozyme loci. Principal component analysis was conducted on the covariance matrix derived from allelic frequencies calculated for each species. Cluster analysis was performed on the first 30 principal components. Results generally support traditional classification of Prunus at the subgeneric level, except for members of subgenus Lithocerasus and two members of subgenus Amygdalus. Prunus glandulosa Thunb., P. japonica Thunb., and P. tomentosa Thunb. of subgenus Lithocerasus and P. triloba Lindl. of subgenus Amygdalus appear to represent primitive species. P. besseyi Bailey and P. pumila L. of subgenus Lithocerasus and P. andersonii of subgenus Amygdalus should be assigned to subgenus Prunus. Placement of its members indicates that subgenus Lithocerasus is an artificial grouping of species that are very different genetically although similar phenotypically. PMID- 24220822 TI - In vitro protein synthesis in isolated microspores of Zea mays at several stages of development. AB - A new procedure has been used providing large and homogenous populations of pollen from maize at different stages of their development. In order to label proteins synthesized during the course of microsporogenesis, a method has been developed that allows an efficient uptake of amino acids in the microspores. Results are presented showing that during pollen development three specific steps are involved: an early period active in protein synthesis, followed by a rest period when starch is accumulated, and a third period preceding the sorting out of mature pollen grains and during which protein synthesis starts again at a relatively low level. New polypeptides, some of which are very basic, appear at the time of starch deposition and accumulate up to the mature stage. PMID- 24220823 TI - Pollen germination in vitro at low temperature in European and Andean tetraploid potatoes. AB - Confined design combined with use of tolerance ratio was used to compare pollen germination capacity at low and high temperature in Andean and European potato material. Four clones of Solanum tuberosum from the European gene pool were compared with four Andean potato clones derived from the breeding program for frost resistance at the International Potato Center (CIP), Lima, Peru. For each clone, the same pollen lot was used throughout each replication. Pollen were germinated at 9 degrees C and 21 degrees C. Fortification of media with potato starch and 14 min preincubation at 25 degrees C were used as variables. The Andean material maintained its germination capacity better than the European material when temperature was decreased. It was possible significantly to distinguish potato clones with low temperature requirement for pollen germination if incubation proceeded germination at 21 degrees C, but not at 9 degrees C. Fortification with starch had no significant effect. PMID- 24220824 TI - Editorial. PMID- 24220825 TI - The good, the bad and the ugly of monitoring programs: Defining questions and establishing objectives. PMID- 24220826 TI - Design elements of monitoring programs: The necessary ingredients for success. AB - Natural resource managers must know the condition of resources entrusted to their steward-ship so that they can maintain unimpaired resources and know when to restore impaired ecosystems. Resource monitoring programs should be designed to provide indications of ecosystem health, define limits of normal variation, identify abnormal conditions, and suggest potential agents of abnormal changes. Development of a conceptual model that identifies all ecosystem components and their relationships is the first step in the design of such a diagnostic monitoring program. Design studies, with field testing on each selected system component, are required to determine the parameters to be measured and to establish monitoring protocols. The best approach to diagnostic monitoring appears to be based on the population dynamics of selected species relative to physical and chemical environmental factors. Both management and monitoring of natural ecosystems need to be recognized as experimental endeavors, and thus approached in an iterative fashion with the scientific method to reduce uncertainty and cost. PMID- 24220827 TI - Statistical approaches to environmental monitoring: Did we teach the wrong things? AB - Two statistical topics that are frequently 'missed' at the level of an applied statistics course or workshop are presented here, along with examples of their use in natural resource monitoring. The first topic deals with use of correlated observations in calculations of variance estimates for a regional mean, required sample size determination, and confidence intervals. Even if correlation values are known only approximately, one can still obtain information on the effect of correlation on the aforementioned computations. The second topic concerns the use of Bayesian techniques in hypothesis testing. Although many authors have advocated its use, Bayesian analysis can be quite complex. Some Bayesian techniques are translated into graphical form that can be readily used by the reader. Both topics represent areas of statistical expertise that can be explored at a very theoretical level; however, there is enough applied material that merits translation for use by those in natural resource monitoring. PMID- 24220828 TI - Data, data everywhere but not a byte to read: Managing monitoring information. AB - The problem of managing scientific information for widespread availability and use can be overwhelming. At Oregon State University, the Quantitative Sciences Group has found a workable solution. The group has developed a Forest Science Data Bank (FSDB) to house data generated by scientists and collaborating researchers in the Andrews Long-Term Ecological Research program. Today the FSDB houses some 2400 data sets from over 350 existing ecological studies and adds about 20 new studies yearly. This paper describes what we have learned in setting up the FSDB as a facility that can be used by researchers who both deposit information in and retrieve information from the FSDB. PMID- 24220829 TI - Quality assurance and quality control in monitoring programs. AB - There are three general characteristics of the data to be collected in a monitoring program that should be met in order to maximize the use and value of the data: the data quality should be known, the data type and quality should be consistent and comparable, and the data should be available and accessible. Potential problems with each of these characteristics are addressed effectively by quality assurance and quality control. One of the most important aspects of quality assurance in a monitoring program is the development of a quality assurance plan, which should identify clearly the quality of the data needed and describe in detail the planned actions to provide confidence that the program will meet its stated objectives.Quality control data, which allow for the quality and suitability of the environmental data to be evaluated and ascertained, should be collected and utilized as an integral part of the QA effort associated with a monitoring program. PMID- 24220830 TI - Monitoring the urban forest: Case studies and evaluations. AB - Urban forestry is a new science, with monitoring techniques that are still evolving. Tree inventory is most commonly practiced, but we are learning to better monitor the benefits and liabilities provided by urban trees. These results are often for political, social, and biological purposes. Although most monitoring is done at the project or local level, examples of state and national projects are given. Quality control procedures are infrequently used, but could substantially improve the accuracy of data collected. PMID- 24220832 TI - Monitoring urban forest canopy cover using satellite imagery. PMID- 24220831 TI - Monitoring urban forest health. AB - Renewed interest in urban forestry has resulted in significant public investment in trees during the past few years, yet comprehensive urban forest monitoring programs are uncommon. Monitoring is an integral component of a program to sustain healthy community forests and long term flows of net benefits. Volunteer based monitoring will promote continued public involvement and support in community forestry. To overcome constraints to monitoring in urban environments, programs must be personally relevant, socially desirable, scientifically credible, and economically feasible. A three-tiered monitoring approach is presented. Canopy cover analysis documents net gains and losses in regional urban forest cover. Simplified detection monitoring uses trained volunteers to better understand tree population dynamics, while intensive monitoring characterizes urban forest functions and stressors. Implementation of an urban forest health initiative to develop, place, and evaluate monitoring programs is advocated. PMID- 24220833 TI - Planning for implementation of long-term resource monitoring programs. AB - Guidelines for the early stages of developing a monitoring program are presented. Jumping right into a monitoring program based on standard protocols and a number of commonly monitored parameters is an attractive idea, but it is unlikely to lead to an intelligent allocation of time and money. Rather, a number of well defined planning steps must be followed before monitoring is begun: 1. Objectives for the program should be well defined. 2. The attributes to be monitored in order to meet objectives should be listed. 3. Methods of monitoring these attributes should be developed. 4. A pilot study should be conducted to determine spatial and temporal variability of the attributes being monitored and the cost of sampling. 5. The results of the pilot study should be carefully evaluated to determine whether program objectives can be met for an acceptable cost. 6. Objectives, attributes to be monitored, and methods should be revised in accordance with the results of the pilot study. PMID- 24220834 TI - Monitoring new forestry. AB - Techniques to monitor growth and mortality of live trees, and longevity of snags were developed and tested on 8 units in the Oregon and Washington Cascades where new forestry (structural retention) cuttings were utilized. Time and costs were quantified. The total area of three aggregated units and five dispersed units was 27.8 ha, with 2407 trees and snags measured on 25.1 ha of sample area. Cost of field work was approximately $4590 (4 person crew at 6 weeks) while costs of data entry, analysis and report writing were approximately $2000 (250 person hours). Monitoring is an important component of adaptive management and is essential if we are to understand the ramifications of new silvicultural systems. PMID- 24220835 TI - Monitoring of growth and yield and response to silvicultural treatments. AB - The objectives for monitoring the growth and yield of forests can range from collecting data to validate current management on an ownership to collecting data at a regional level to develop models, measure treatment response, or observe long-term growth trends. Traditional inventory and research data each have drawbacks for observing growth and yield and treatment response. The actual design of a monitoring system should try to minimize these problems, but will depend on the specific objectives. Monitoring of operations may take an inventory type approach, while gathering regional information to build models requires a design more like research. Each organization must be responsible for monitoring its own operations, however, cooperatives offer a viable and cost effective alternative to gathering regional growth and response data. Monitoring programs will lead to confidence and credibility in management practices and in the use of tested models. PMID- 24220836 TI - Beyond the Guidelines: Practical lessons for monitoring. AB - A series of workshops have provided extensive feedback on a recently published manual, Monitoring Guidelines to Evaluate Effects of Forestry Activities on Streams in the Pacific Northwest and Alaska (Guidelines) (MacDonald et al., 1991). These workshops and other discussions have led to the identification of fourteen additional 'lessons' for monitoring. These lessons are concepts which either were not incorporated into the Guidelines, were not sufficiently emphasized, or which are needed to put the Guidelines in context. The topics include: monitoring as a continuum; defining objectives and hypotheses; peer review; uncertainty and risk; upslope vs. instream monitoring; photo sequences; scale considerations; data storage, data interpretation, and data base management; 'activities monitoring'; and personal commitment as a critical component in monitoring projects. Many of these lessons might appear self evident, but our experience indicates that they are often ignored. Like the Guidelines, these lessons are widely applicable and should be explicitly recognized when formulating and conducting monitoring projects. PMID- 24220837 TI - The need for long-term stream monitoring programs in forest ecosystems of the Pacific Northwest. AB - Concepts, planning and design procedures are examined that are needed in the development of long-term stream monitoring programs in forested regions. A long term stream monitoring program is viewed as the key component for bringing together management organizations, researchers and decision-makers to improve the management of natural resources. The keystones of such ecosystem monitoring are long-term data records that provide the basis for analysis of environmental assessment objectives, predictions and analysis of outcomes which in-turn can be used to modify and improve future projects. Management organizations that initiate long-term monitoring programs are urged to use monitoring actions and information to facilitate decision-making processes that pertain to conserving and allocating resources for future beneficial uses. Recommendations are provided for careful planning and definition of interactive activities of monitoring programs and that should provide information feedbacks that can be used to evaluate issues pertaining to beneficial uses of resources. Procedural requirements and literature sources are suggested for developing long-term stream monitoring programs. They include reviews of background and historical information to provide precise definitions of long-term objectives, planning considerations and monitoring methods. Examples are given of specific procedures that need to be identified during the planning process. They include the application of management standards to variable conditions encountered within natural ecosystems and the detection of the timing of recovery phases of stream ecosystem development following a disturbance. These procedures are viewed as being essential for improving applications of management standards and perceived thresholds to stream and watershed ecosystems monitoring programs. PMID- 24220838 TI - Monitoring in the Tualatin River Basin to assess the effectiveness of the Oregon Forest Practicers Program: Preliminary results of phosphorus monitoring. AB - The Oregon Department of Forestry is a designated management agency to provide a forestry program to assist in bringing the Tualatin River into complicance with pH and dissolved oxygen water quality standards. The Oregon Environmental Quality Commission set a total maximum daily load (TMDL) of 70 ug/l total phosphorus to control algae growth and meet these standards. The Department of Forestry has a basin effectiveness monitoring plan to determine that the Oregon Forest Practice Rules' BMPs are maintaining adequate control of phosphorus loadings from forest operations. Three sites monitored during May to October of 1990 were augmented by eight more sites in 1991. As laboratory methods were refined, the results became more accurate. The 1991 monitoring showed lower phosphorus levels that were consistent for each tributary. Mean total phosphorus levels ranged from 17 to 65 ug/l. Preliminary field reconnaissance suggests a correlation between phosphorus levels and underlying geology. Concentrations were lowest at sites underlain by tertiary intrusive basalts, next higher for sites with terrestrial basalt, next higher for one site with a basalt-sandstone bedrock mix, and highest for sites underlain predominately by sandstone. These results may be modified by 1992 monitoring and further analysis. PMID- 24220839 TI - Water quality monitoring in Washington's Timber/Fish/Wildlife program. AB - The Timber, Fish, and Wildlife program (TFW) in Washington is a consensus approach to implementing reforms in forest practice regulations involving industrial timberland owners, state agencies, environmental groups, Indian tribes, and non-industrial forest landowners. A cooperative monitoring and research effort (CMER) has been included as a part of this program. Technical projects undertaken by CMER are overseen by a series of steering committees, one of which is the Water Quality Steering Committee. Projects currently being addressed by the Water Quality Steering Committee include: forestry impacts on water temperature, water quality impacts from forestry derived sediment, use of bio-indicators to assess the water quality impacts of forest practices, and the effect of forest chemical applications on water quality. A close link between the research efforts in TFW and the procedure for implementing regulatory change has greatly improved the responsiveness of the rule making process to new information. Results from the water temperature and forest chemical work is currently being incorporated into the forest practice regulations. PMID- 24220840 TI - Multimedia environmental monitoring: 50 years at Hanford. AB - Environmental monitoring has been an ongoing activity on the U.S. Department of Energy's Hanford Site in southeastern Washington for almost 50 years. Objectives are to detect and assess potential impacts of Site operations on air, surface and ground waters, foodstuffs, fish, wildlife, soil and vegetation. Data from monitoring effects are used to calculate the overall radiological dose to humans working onsite or residing in nearby communities. In 1989, measured Hanford Site perimeter concentrations of airborne radionuclides were below applicable guidelines. Concentrations of radionuclides and nonradiological water quality in the Columbia River were in compliance with applicable standards. Foodstuffs irrigated with river water taken downstream of the Site showed radionuclide levels that were similar to those found in foodstuffs from control areas. Low levels of (137)Cs and (90)Sr in most onsite wildlife samples and concentrations of radionuclides in soils and vegetation from on- and offsite locations were typical of those attributable to worldwide fallout. The calculated dose potentially received by a maximally exposed individual (i.e., based on hypothetical, worst-case assumptions for all routes of exposure) in 1989 (0.05 mrem/yr) was similar to those calculated for 1985 through 1988.In addition to monitoring radioactivity in fish and wildlife, population numbers of key species are determined. Chinook salmon (Oncorhynchus tshawytscha) spawning in the Columbia River at Hanford has increased in recent years with a concomitant increase in winter roosting activity of bald eagles (Haliaeetus leucocephalus). An elk (Cervus elaphus) herd, established by immigration in 1972, is also increasing. The Hanford Site currently serves as a refuge for Canada goose (Branta canadensis), great blue heron (Ardea herodias), and various plants and other animals, e.g., mule deer (Odocoileus hemionus), and coyotes (Canis latrans). PMID- 24220841 TI - Potential biases in site and species selection for ecological monitoring. AB - A number of the contributions to this workshop (particularly in the session on biodiversity and population monitoring) have stressed the importance of choosing appropriate species and locations for ecological monitoring. This is of pragmatic necessity: it is impossible to monitor all species at all locations. The purpose of this note is to caution against some possible pitfalls in the selection of species and sites. These pitfalls are a result of the statistical concept of regression. PMID- 24220842 TI - Regional monitoring with plot networks. AB - The national Forest Health Detection Monitoring Program, was initiated first in the eastern United States, in partial response to findings from the National Acid Precipitation Assessment Program. This paper presents an overview of that program as it is extended from its focus in the eastern United States to a national program. The paper describes the basic concerns driving the program; presents a summary of the sampling design; emphasizes the importance of proper planning, beginning with an information needs assessment with the various data and information users; and discusses the process of selecting data elements and indicators of change to monitor. PMID- 24220843 TI - Monitoring global change: Comparison of forest cover estimates using remote sensing and inventory approaches. AB - Satellite-based remote sensing offers great potential for frequent assessment of forest cover over broad spatial scales, however, calibration and validation using ground-based surveys are needed. In this study, forest cover estimates for the United States from a recently developed land surface cover map generated from satellite remote sensing data were compared to state-level inventory data from the U.S. National Resources Planning Act Timber Database. The land cover map was produced at the U.S. Geological Survey EROS Data Center and is based on imagery from the AVHRR sensor (spatial resolution ~1.1 km). Vegetation type was classified using the temporal signal in the Normalized Difference Vegetation Index derived from AVHRR data. Comparisons revealed close agreement in the estimate of forest cover for extensively forested states with large polygons of relatively similar vegetation such as Oregon. Larger forest cover differences were observed in other states with some regional patterns in the level of agreement apparent.Comparisons in inventory- and remote sensing-based estimates of current forested area with potential vegetation maps indicated the magnitude of past land use change and the potential for future changes. The remote sensing approach appears to hold promise for conducting surveys of forest cover where inventory data are limited or where rates of vegetation change, due to human or climatic factors, are rapid. PMID- 24220844 TI - What does it all mean? AB - Now that the concerns, issues, ideas and constraints have been discussed, how does all of this come together? There are three basic questions we should ask.* Can we improve natural resource management through monitoring?* Will those that make the decisions listen?* Will they use the generated data in their decision?I am going to relate to you what has happened in California over the last fifteen years. I believe it will point out that the answer to the three questions are a resounding yes, with some qualifications and some bumpy roads along the way. PMID- 24220845 TI - The concept of the certification system of the German Cancer Society and its impact on gynecological cancer care. AB - PURPOSE: This article describes the status of gynecological cancer care in Germany and gives an overview of the certification of gynecological cancer care by the German Cancer Society (Deutsche Krebsgesellschaft DKG). The DKG certifies cancer centers to promote a high-quality level in the treatment of oncological patients. METHODS: Searches were conducted in PubMed and ScienceDirect to identify the relevant literature. Catalog of requirements for centers certification as well as benchmark reports were used to characterize cancer care in centers certified by DKG. RESULTS AND CONCLUSIONS: The certification system of the DKG has been developed to ensure comprehensive care for cancer patients in Germany. The criteria for certification are based on interdisciplinary and inter professional care conforming to guidelines and specialist expertise. These requirements have been shown to improve structural and process quality, and thus satisfaction and health outcomes in patients. PMID- 24220846 TI - Spontaneous bilateral tubal pregnancy following hysterosalpingography. PMID- 24220847 TI - CO2 laser debonding of a ceramic bracket bonded with orthodontic adhesive containing thermal expansion microcapsules. AB - We have been studying an easy bracket debonding method using heating of an orthodontic adhesive containing thermal expansion microcapsules. However, heating with a high-temperature heater brings obvious risks of burns around the oral cavity. Thus, we examined safer and more effective bracket debonding methods. The purpose of this in vitro study was to examine the reduction in debonding strength and the time taken using a bracket bonded with an orthodontic adhesive containing thermal expansion microcapsules and a CO2 laser as the heating method while maintaining safety. Ceramic brackets were bonded to bovine permanent mandibular incisors using bonding materials containing various microcapsule contents (0, 30, and 40 wt%), and the bond strengths were measured after laser irradiation for 4, 5, and 6 s and compared with nonlaser-treated groups. Subsequently, the temperature in the pulp chamber during laser irradiation was measured. After laser irradiation for 5 or 6 s, the bond strengths of the adhesive containing 40 wt% microcapsules were significantly decreased to ~0.40 - 0.48-fold (4.6-5.5 MPa) compared with the nonlaser groups. The mean temperature rise of the pulp chamber was 4.3 degrees C with laser irradiation for 6 s, which was less than that required to induce pulp damage. Based on these results, we conclude that the combined use of a CO2 laser and an orthodontic adhesive containing thermal expansion microcapsules can be effective and safe for debonding ceramic brackets with less enamel damage or tooth pain. PMID- 24220849 TI - Ranging behavior of eastern hoolock gibbon (Hoolock leuconedys) in a northern montane forest in Gaoligongshan, Yunnan, China. AB - Generally, food abundance and distribution exert important influence on primate ranging behavior. Hoolock gibbons (genus Hoolock) live in lowland and montane forests in India, Bangladesh, Myanmar and China. All information about hoolock gibbons comes from studies on western hoolock gibbons (Hoolock hoolock) living in lowland forest. Between August 2010 and September 2011, we studied the ranging behavior of one habituated group of eastern hoolock gibbon (H. leuconedys) living in a seasonal montane forest in Gaoligongshan, Yunnan, China. Results show that the study group did not increase foraging effort, calculated in this study as the daily path length, when fruit was less available. Instead, the gibbons fed more on leaves and decreased traveling to conserve energy. They relied heavily on a single food species in most study months which was patchily distributed within their total (14-month) home range, and during most months they used only a small portion of their total home range. In order to find enough food, the group shifted its monthly home range according to the seasonal availability of food species. To satisfy their annual food requirements, they occupied a total home range of 93 ha. The absence of neighboring groups of gibbons and the presence of tsaoko cardamom (Amomum tsaoko) plantations may also have influenced the ranging behavior of the group. Further long-term studies of neighboring groups living in intact forests are required to assess these effects. PMID- 24220850 TI - Activation of early phase of adipogenesis through Kruppel-like factor KLF9 mediated, enhanced expression of CCAAT/enhancer-binding protein beta in 3T3-L1 cells. AB - In this study, we found that Kruppel-like factor (KLF) 9 activate the progression of the early phase of adipocyte differentiation in mouse adipocytic 3T3-L1 cells. KLF9 mRNA was detected in preadipocytes; and its level increased after the initiation of adipocyte differentiation, reached its maximum at 1h, and gradually decreased thereafter. Functional suppression of KLF9 mRNA by its siRNAs repressed the accumulation of the intracellular lipids with a reduction in the expression of CCAAT/enhancer-binding protein (C/EBP) beta, but not in that of C/EBPdelta. In contrast, C/EBPbeta and C/EBPdelta did not affect the expression of KLF9 in 3T3 L1 cells. A chromatin immunoprecipitation assay revealed that KLF9 bound the KLF binding element at position -874 of the mouse C/EBPbeta promoter. Moreover, the ability of KLF9 to bind to this element was enhanced, with a peak at 1-2h after the initiation of adipogenesis, whose profile well resembled that of the expression of the C/EBPbeta gene in 3T3-L1 cells. These results indicate that KLF9 activated the early phase of adipogenesis by enhancing the expression of the C/EBPbeta gene in 3T3-L1 cells. PMID- 24220848 TI - Transcutaneous laser treatment of leg veins. AB - Leg telangiectasias and reticular veins are a common complaint affecting more than 80% of the population to some extent. To date, the gold standard remains sclerotherapy for most patients. However, there may be some specific situations, where sclerotherapy is contraindicated such as needle phobia, allergy to certain sclerosing agents, and the presence of vessels smaller than the diameter of a 30 gauge needle (including telangiectatic matting). In these cases, transcutaneous laser therapy is a valuable alternative. Currently, different laser modalities have been proposed for the management of leg veins. The aim of this article is to present an overview of the basic principles of transcutaneous laser therapy of leg veins and to review the existing literature on this subject, including the most recent developments. The 532-nm potassium titanyl phosphate (KTP) laser, the 585-600-nm pulsed dye laser, the 755-nm alexandrite laser, various 800-983-nm diode lasers, and the 1,064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser and various intense pulsed light sources have been investigated for this indication. The KTP and pulsed dye laser are an effective treatment option for small vessels (<1 mm). The side effect profile is usually favorable to that of longer wavelength modalities. For larger veins, the use of a longer wavelength is required. According to the scarce evidence available, the Nd:YAG laser produces better clinical results than the alexandrite and diode laser. Penetration depth is high, whereas absorption by melanin is low, making the Nd:YAG laser suitable for the treatment of larger and deeply located veins and for the treatment of patients with dark skin types. Clinical outcome of Nd:YAG laser therapy approximates that of sclerotherapy, although the latter is associated with less pain. New developments include (1) the use of a nonuniform pulse sequence or a dual-wavelength modality, inducing methemoglobin formation and enhancing the optical absorption properties of the target structure, (2) pulse stacking and multiple pass laser treatment, (3) combination of laser therapy with sclerotherapy or radiofrequency, and (4) indocyanin green enhanced laser therapy. Future studies will have to confirm the role of these developments in the treatment of leg veins. The literature still lacks double-blind controlled clinical trials comparing the different laser modalities with each other and with sclerotherapy. Such trials should be the focus of future research. PMID- 24220851 TI - Enhancement of expression of survivin promoter-driven CD/TK double suicide genes by the nuclear matrix attachment region in transgenic gastric cancer cells. AB - This work aimed to study a novel transgenic expression system of the CD/TK double suicide genes enhanced by the nuclear matrix attachment region (MAR) for gene therapy. The recombinant vector pMS-CD/TK containing the MAR-survivin promoter CD/TK cassette was developed and transfected into human gastric cancer SGC-7901 cells. Expression of the CD/TK genes was detected by quantitative real-time PCR (qPCR) and Western blot. Cell viability and apoptosis were measured using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. When the MAR fragment was inserted into the upstream of the survivin promoter, the qPCR result showed that the expression of the CD/TK genes significantly increased 7.7-fold in the transgenic SGC-7901 cells with plasmid pMS-CD/TK compared with that without MAR. MTT and flow cytometry analyses indicated that treatment with the prodrugs (5-FC+GCV) significantly decreased the cellular survival rate and enhanced the cellular apoptosis in the SGC-7901 cells. The expression of the CD/TK double suicide genes driven by the survivin promoter can be enhanced by the MAR fragment in human gastric cancer cells. PMID- 24220852 TI - Pheno-Pub: a total support system for the publication of mouse phenotypic data on the web. AB - We have developed an open-source database system named "Pheno-Pub" to support a series of data-handling and publication tasks, including statistical analyses, data review, and web site construction, for mouse phenotyping experiments. This system is composed of three applications. "Mou-Stat" provides semiautomatic statistical analyses for a batch of phenotypic data, including a variety of conditions for group comparisons (e.g., different scales of measurement parameters). "Genotype Viewer" and "Strain Viewer" provide representation of genotype-driven and measurement parameter-driven views of phenotypic data; they highlight significant differences in genotypes and between strains, respectively. Direct links from the Strain Viewer web site to the Genotype Viewer web site provide flexible navigation in the exploration of phenotypic data. With these publication tools, phenotypic data can be made available on the Internet by simple operations. This system is expandable for a wide range of uses in phenotypic comparative analyses, including comparisons among different genotypes and strains and comparisons among groups exposed to different environmental conditions. Finally, Pheno-Pub provides advanced usability for both producers of experimental data and consumers of phenotypic information. Therefore, Pheno-Pub contributes significantly to the publication of data in various fields of phenotyping research and to broad data sharing, thereby promoting the understanding of the functions of the entire mouse genome. PMID- 24220853 TI - A high-throughput image-based screen for the identification of Bax/Bak independent caspase activators against drug-resistant cancer cells. AB - Despite the use of new generation target specific drugs or combination treatments, drug-resistance caused by defective apoptosis signaling remains a major challenge in cancer treatment. A common apoptotic defect in drug-resistant tumor is the failure of cancer cells to undergo Bax/Bak-dependent mitochondrial permeabilization due to impaired signaling of Bcl-2 family proteins. Therefore, Bax and Bak-independent caspase-activating compounds appear to be effective in killing such tumor cells. An image-based cellular platform of caspase sensors in Bax and Bak deficient background allowed us to identify several potential Bax/Bak independent caspase-activating compounds from a limited high-throughput compound screening. FRET-based caspase sensor probe targeted at the nucleus enabled accurate and automated segmentation, yielding a Z-value of 0.72. Some of the positive hits showed promising activity against drug-resistant human cancer cells expressing high levels of Bcl-2 or Bcl-xL. Using this approach, we describe thiolutin, CD437 and TPEN as the most potentially valuable drug candidates for addressing drug-resistance caused by aberrant expression of Bcl-2 family proteins in tumor cells. The screen also enables the quantification of multiparameter apoptotic events along with caspase activation in HTS manner in live mode, allowing characterization of non-classical apoptosis signaling. PMID- 24220854 TI - The DAPK family: a structure-function analysis. AB - DAP-kinase (DAPK) is the founding member of a family of highly related, death associated Ser/Thr kinases that belongs to the calmodulin (CaM)-regulated kinase superfamily. The family includes DRP-1 and ZIP-kinase (ZIPK), both of which share significant homology within the common N-terminal kinase domain, but differ in their extra-catalytic domains. Both DAPK and DRP-1 possess a conserved CaM autoregulatory domain, and are regulated by calcium-activated CaM and by an inhibitory auto-phosphorylation within the domain. ZIPK's activity is independent of CaM but can be activated by DAPK. The three kinases share some common functions and substrates, such as induction of autophagy and phosphorylation of myosin regulatory light chain leading to membrane blebbing. Furthermore, all can function as tumor suppressors. However, they also each possess unique functions and intracellular localizations, which may arise from the divergence in structure in their respective C-termini. In this review we will introduce the DAPK family, and present a structure/function analysis for each individual member, and for the family as a whole. Emphasis will be placed on the various domains, and how they mediate interactions with additional proteins and/or regulation of kinase function. PMID- 24220855 TI - The DAP-kinase interactome. AB - DAP-kinase (DAPK) is a Ca(2+)/calmodulin regulated Ser/Thr kinase that activates a diverse range of cellular activities. It is subject to multiple layers of regulation involving both intramolecular signaling, and interactions with additional proteins, including other kinases and phosphatases. Its protein stability is modulated by at least three distinct ubiquitin-dependent systems. Like many kinases, DAPK participates in several signaling cascades, by phosphorylating additional kinases such as ZIP-kinase and protein kinase D (PKD), or Pin1, a phospho-directed peptidyl-prolyl isomerase that regulates the function of many phosphorylated proteins. Other substrate targets have more direct cellular effects; for example, phosphorylation of the myosin II regulatory chain and tropomyosin mediate some of DAPK's cytoskeletal functions, including membrane blebbing during cell death and cell motility. DAPK induces distinct death pathways of apoptosis, autophagy and programmed necrosis. Among the substrates implicated in these processes, phosphorylation of PKD, Beclin 1, and the NMDA receptor has been reported. Interestingly, not all cellular effects are mediated by DAPK's catalytic activity. For example, by virtue of protein-protein interactions alone, DAPK activates pyruvate kinase isoform M2, the microtubule affinity regulating kinases and inflammasome protein NLRP3, to promote glycolysis, influence microtubule dynamics, and enhance interleukin-1beta production, respectively. In addition, a number of other substrates and interacting proteins have been identified, the physiological significance of which has not yet been established. All of these substrates, effectors and regulators together comprise the DAPK interactome. By presenting the components of the interactome network, this review will clarify both the mechanisms by which DAPK function is regulated, and by which it mediates its various cellular effects. PMID- 24220857 TI - Microtubules and epithem-cell morphogenesis in hydathodes of Pilea cadierei. AB - When cell divisions have ceased, the epithem of the hydathodes of Pilea cadierei Gagnep. et Guill. consists of small polyhedral cells exhibiting a meristematic appearance, and completely lacks intercellular spaces. The cortical microtubules in epithem cells exhibit a unique organization: they are not scattered along the whole wall surface but form groups lying at some distance from each other. In sections, from two to eight groups of microtubules can be observed, each lining a wall region averaging between 0.5 and 1.5 MUm in length. These groups represent sections of microtubule bundles girdling a major part or the whole of the cell periphery. They are connected to one another by anastomoses, forming a microtubular reticulum. The assembly of microtubule bundles is followed by the appearance of distinct local thickenings in the adjacent wall areas. The cellulose microfibrils in the thickenings are deposited in parallel to the underlying microtubules. Gradually, the vacuolating epithem cells undergo swelling, except for the areas bounded by the wall thickenings. Since the latter, and actually their constituent bundles of cellulose microfibrils, cannot extend in length the differential cell growth results in schizogenous formation of intercellular spaces between contiguous cell walls at their thickened regions. The spaces then broaden and merge to become an extensive intercellular space system. As a result of the above processes, the epithem cells become constricted and finally deeply lobed. The observations show that (i) the cortical microtubules are intimately involved in the morphogenesis of the epithem cells and (ii) the initiation and development of the epithem intercellular spaces is a phenomenon directly related to cell morphogenesis and therefore to the cortical microtubule cytoskeleton. The sites of initiation of these spaces are highly predictable. PMID- 24220858 TI - Monoclonal antibodies to sperm surface antigens of the brown alga Fucus serratus exhibit region-, gamete-, species- and genus-preferential binding. AB - A panel of twelve monoclonal antibodies (MAbs), designated FS1 to FS12, have been raised against surface antigens of Fucus serratus sperm. The antibodies were selected on the basis that they show region-, gamete-, species- or genus preferential binding. Indirect immunofluorescence shows that the antigens bound by the MAbs are distributed non-randomly over the cell surface. Seven MAbs (FS1, FS3, FS4, FS6, FS8, FS9, FS10) bind antigens located primarily on the cell body, while the others (FS2, FS5, FS7, FS11, FS12) bind antigens located primarily on the anterior flagellum. Of the MAbs that label the anterior flagellum, FS2, FS5, FS7 and FS12 form a 'halo' at the perimeter of the flagellum. Electron microscopic-immunogold studies indicate that the 'halo' results from labelling of the mastigonemes, as opposed to the flagellar plasmamembrane. Gamete-preferential binding of antibodies was detected using an enzyme-linked immunosorbent assay with egg membrane vesicles. Eight of the MAbs bind sperm antigens not common to eggs, though FS2, FS4, FS5 and FS9 bind antigens present on both sperm and eggs. In studies of species- and genus-specificity FS2, FS3, FS5, FS6, FS7, FS8, FS10, FS11 and FS12 exhibit genus-preferential binding, labelling sperm of F. serratus and F. vesiculosus more intensely than that of Ascophyllum nodosum. Only FS10 showed marked species-preferential binding, labelling sperm of F. serratus much more intensely than that of F. vesiculosus. PMID- 24220856 TI - Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel. AB - Paclitaxel is a mainstay of treatment for many solid tumors, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miRNAs associated with cancer cell line response to paclitaxel and to evaluate these miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the expression of 335 unique miRNAs in 40 human cancer cell lines selected from the NCI panel. We then integrated miRNA expression data with publicly available paclitaxel-sensitivity (GI50) data for each of the 40 cell lines to identify miRNAs associated with paclitaxel sensitivity. Ovarian cancer cell lines with differential miRNA expression and paclitaxel sensitivity were transiently transfected with miRNA precursors and inhibitors, and the effects on in vitro cell paclitaxel sensitivity were evaluated. Pearson's correlation identified 2 miRNAs (miR-367 and miR-30a-5p) associated with the NCI40 cell line in vitro paclitaxel response (P<0.0003). Ovarian cancer cells were selected based on the association between paclitaxel sensitivity and miR-367/miR-30a-5p expression. Overexpression of miR 367 in the paclitaxel-sensitive cells [PA1; IC50, 1.69 nM, high miR-367 (2.997), low miR-30a-5p (-0.323)] further increased paclitaxel sensitivity, whereas miR 367 depletion decreased paclitaxel sensitivity. In contrast, overexpression and depletion of miR-30a-5p in the paclitaxel-resistant cells [OVCAR4; IC50, 17.8 nM, low miR-367 (-0.640), high miR-30a-5p (3.270)] decreased and increased paclitaxel sensitivity, respectively. We identified and successfully targeted miRNAs associated with human cancer cell line response to paclitaxel. Our strategy of integrating in vitro miRNA expression and drug sensitivity data may not only aid in the characterization of determinants of drug response but also in the identification of novel therapeutic targets to increase activity of existing therapeutics. PMID- 24220859 TI - A morphometric analysis of the phloem-unloading pathway in developing tobacco leaves. AB - A morphometric analysis of developing leaves of Nicotiana tabacum L. was conducted to determine whether imported photoassimilates could be unloaded by symplastic transport and whether interruption of symplastic transport could account for termination of import. Five classes of veins were recognized, based on numbers of cells in transverse section. Photoassimilate is unloaded primarily from Class III veins in tissue nearing the end of the sink phase of development. Smaller veins (Class IV and V) do not transport or unload photoassimilate in sink tissue because the sieve elements of these veins are immature until after the tissue stops importing. In Class III veins the sieve element-companion cell (SE CC) complexes are surrounded by phloem parenchyma which abuts the bundle sheath. Along the most obvious unloading route, from SE-CC complex to phloem parenchyma to bundle sheath to mesophyll cells, the frequency of plasmodesmata at each interface increases. To determine whether this pattern of plasmodesmatal contact is consistent with symplastic unloading we first demonstrated, by derivation from Fick's law that the rate of diffusion from a compartment is proportional to a number N which is equal to the ratio of surface area to volume of the compartment multiplied by the frequency of pores (plasmodesmata) which connect it to the next compartment. N was calculated for each compartment within the vein which has the SE-CC complex as its center, and was shown to be statistically the same in all cases except one. These observations are consistent with a symplastic unloading route. As the leaf tissue matures and stops importing, plasmodesmatal frequency along the unloading route decreases and contact area between cells also decreases as intercellular spaces enlarge. As a result, the number of plasmodesmata between the SE-CC complex and the first layer of mesophyll cells declines in nonimporting tissue to 34% of the number found in importing tissue, indicating that loss of symplastic continuity between the phloem and surrounding cells plays a role in termination of photoassimilate unloading. PMID- 24220860 TI - Dinitrogenase reductase (Fe-protein) of nitrogenase in the cyanobacterial symbionts of three Azolla species: Localization and sequence of appearance during heterocyst differentiation. AB - Transmission electron microscopy and immunocytological labeling were used to study the distribution and ontological occurrence of dinitrogenase reductase (Fe protein) of nitrogenase in cyanobacterial symbionts within young leaves of the water-ferns Azolla filiculoides Lamarck, A. caroliniana Willdenow, and A. pinnata R. Brown. Rabbit anti-dinitrogenase reductase antisera and goat anti-rabbit immunoglobulin G antibody conjugated to colloidal gold were used as probes. Western blot analyses showed that a polypeptide of approx. 36 kDa (kdalton) was recognized in the symbionts of all three Azolla species and that the polyclonal sera used were monospecific. In all symbionts, nitrogenase was immunologically recognizable within heterocysts. It was absent from vegetative cells, and also from the akinetes of the A. caroliniana and A. pinnata symbionts. The differentiation of vegetative cells into heterocysts in all three symbionts was initiated by formation of additional external cell-wall layers and narrowing of the neck followed by loss of glycogen, mild vesiculation of thylakoid membranes, and the appearance of polar nodules. No nitrogenase was detected at these early stages, but it appeared in the intermediate proheterocyst stage concomitantly with the formation of contorted membranes, and reached the strongest labeling in mature heterocysts, containing extensive tightly packed membranes. Nitrogenase was evenly distributed throughout heterocysts except at the polar regions, which contained honey-comb configurations and large polar nodules. With increased age of the A. caroliniana and A. pinnata symbionts, heterocysts became highly vesiculated, with a concomitant decrease in the amount of nitrogenase detected. PMID- 24220861 TI - An alternative explanation for plant growth promotion by bacteria of the genus Azospirillum. AB - Experiments were performed to identify the substances that are excreted by the soil bacterium Azospirillum brasilense Sp7 and that were reported to stimulate the formation of lateral roots and of root hairs of grasses. Azospirillum forms indole-3 acetic acid (IAA) but only in the late stationary growth phase or when tryptophan is present in the medium, but not in continuous cultures or in the logarithmic growth phase of batch cultures. Formation of IAA by Azospirillum requires aerobic conditions. Nitrite can replace IAA in several phytohormone assay, and is even more active than IAA in a test with wheat root segments in which the increase of wet weight is determined. Higher amounts of nitrite are necessary for activity in other classical auxin assays. Nitrite shows 40-60% of the activity of IAA in the straight-growth test of Avena coleoptiles and in the formation of C2H4 by pea epicotyl segments. Like IAA, nitrite is inactive in promoting C2H4 formation by ripe apple tissues. Since nitrite alone can hardly exert phytohormonal effects, it is postulated that nitrite reacts with a substance in the cells and that a product formed by this reaction functions as auxin. Such a substance could be ascorbate. Exogenously added ascorbate enhances the rate of nitrite-dependent C2H4 formation by pea epicotyl sections and the nitrite-dependent increase in the wet weight of wheat root segments. Nitrite is formed by nitrate respiration of Azospirillum. The findings that nitrite can have phytohormonal effects offers an alternative explanation of the promotion of the growth of roots and the enhancement of mineral uptake of grasses by Azospirillum. Indole-acetic acid completely and nitrite partly substitute for an inoculation with Azospirillum in an assay where the increase of the dry weight of intact wheat roots is determined after an incubation for 10 d. Nitrite and IAA are, therefore, possibly the only factors causing an enhancement of the growth of roots of grasses. PMID- 24220862 TI - Bisulfite interacts with binding sites of the auxin-transport inhibitor N-1 naphthylphthalamic acid. AB - The affinity of the auxin-transport inhibitor N-1-naphthylphthalamic acid (NPA) for membrane particles as well as for solubilized binding sites from Cucurbita pepo L. hypocotyls was reduced by low concentrations of bisulfite (half-maximal inhibition at 2.10(-3)-3.10(-3) M). Two membrane fractions obtained by sedimentation aided with polyethylene glycol showed differential sensitivity to bisulfite. Other oxidizing or reducing substances tested at 1 mM had no effect, except for N-ethylmaleimide (80% inhibition) and iodine (complete inhibition), both of which reduced the number of binding sites but not their affinity. Addition of bisulfite to either the isoalloxane ring of flavoproteins or to pyridoxal phosphate or quinones is proposed as a possible mechanism of action. Sulfur dioxide, at concentrations measured in polluted air, can lead to bisulfite concentrations in plant tissue sufficient to interfere with NPA-binding sites and hence with auxin transport. PMID- 24220863 TI - Indication of transthylakoid proton-fluxes in Aegopodium podagraria L. by light induced changes of plasmalemma potential, chlorophyll fluorescence and light scattering. AB - The time course of the responses of chlorophyll fluorescence in leaves of Aegopodium podagraria to changes in irradiance does not necessarily show the time constant of thylakoid energization at energy fluence rates below 10-25 W.m(-2). In addition, other measures of thylakoid energization, such as lightscattering at 532 nm and the responses to saturating flashes, show that the related component disappears from these signals at low fluence rates, but not necessarily all together at the same fluence rate. However, this time constant still appears in the light-induced responses of the plasmalemma potential. This implies that the effect on the electrogenic proton pump in the plasmalemma is the most sensitive indicator of proton fluxes into the inner thylakoid space. These results are a further indication that energy-quenching is coupled ther indication that energy quenching is coupled to transthylakoid proton fluxes via an intermediate, which is not active in Aegopodium podagraria at low irradiances. PMID- 24220864 TI - Characterization of vacuolar polypeptides of barley mesophyll cells by two dimensional gel electrophoresis and by their affinity to lectins. AB - Vacuoles were isolated from primary leaves of barley (Hordeum vulgare L.) by mechanical breakage of protoplasts, and their polypeptide composition analyzed by two-dimensional gel electrophoresis. Vacuoplasts which consist of the vacuole, a portion of the plasmalemma and of the cytoplasma were prepared from protoplasts by ultracentrifugation. By comparing the vacuolar polypeptide pattern with polypeptide patterns of isolated chloroplasts and of vacuoplasts, vacuolar polypeptides could clearly be distinguished from polypeptides derived from cross contaminating cell compartments. At least 14 polypeptides of apparent molecular mass between 12 and 76 kilodaltons and an isoelectric point between 4.5 and 7.6 could be attributed to the tonoplast fraction of the vacuole, and 35 polypeptides to the soluble fraction of the vacuole. Several lectins with different specificity were employed to characterize the degree and nature of glycosylation of vacuolar polypeptides. Concanavalin A bound to a large number of polypeptides. Three out of the 14 tonoplast polypeptides exhibited detectable carbohydrate moieties and almost two-thirds of the surveyed soluble polypeptides were glycosylated. PMID- 24220865 TI - Channel-mediated K(+) flux in barley aleurone protoplasts. AB - Gibberellic acid (GA3) stimulates K(+) efflux from the barley (Hordeum vulgare L. cv. Himalaya) aleurone. We investigated the mechanism of K(+) flux across the plasma membrane of aleurone protoplasts using patch-clamp techniques. Potassium ion currents, measured over the entire surface of the protoplast plasma membrane, were induced when the electrochemical gradient for K(+) was inward (into the cytoplasm). The magnitude and voltage-dependence of this inward current were the same in protoplasts treated with GA3 and in control protoplasts (no GA3). Inward currents activated by negative shifts in the membrane potential (EM) from the Nernst potential for K(+) (EK) showed membrane conductance to be a function of the electrochemical gradient (i.e. EM-EK). Single-channel influx currents of K(+) were recorded in small patches of the plasma membrane. These channels had a single-channel conductance of 5-10 pS with 100 mM K(+) on the inside and 10 mM K(+) on the outside of the plasma membrane. Single-channel currents, like whole cell currents, were the same in protoplasts treated with GA3 and control protoplasts. Voltage-gated efflux currents were found only in protoplasts tha thad been incubated without GA3. We conclude that K(+) influx in the aleurone is mediated by channels and these membrane proteins are not greatly effected by GA3. PMID- 24220866 TI - Transport of phenylalanine into vacuoles isolated from barley mesophyll protoplasts. AB - The energy-dependent transport of phenylalanine into isolated vacuoles of barley (Hordeum vulgare L.) mesophyll protoplasts has been studied by silicone-layer floatation filtering. The uptake of this aromatic amino acid into the vacuolar compartment is markedly increased by MgATP, showing saturation kinetics; the K m values were 0.5 mM for MgATP and 1.2 mM for phenylalanine. V max for phenylalanine transport was estimated to 140 nmol phenylalanine.(mg.Chl)(-1).h( 1). The transport shows a distinct pH optimum at 7.3 and is markedly inhibited by 40 mM nitrate. Azide (1 mM) and vanadate (400 MUM) had no or little effect on rates of transport while p-fluorophenylalanine seemed to be an effective inhibitor, indicating a possible competition at an amino-acid carrier. Ionophores such as valinomycin, nigericin or gramicidin were strong inhibitors of phenylalanine transport, indicating that this process is coupled to both the transmembrane pH gradient (DeltapH) and the transmembrane potential (DeltaPsi). PMID- 24220867 TI - Time courses for phytochrome-induced enzyme levels in phenylpropanoid metabolism (phenylalanine ammonia-lyase, naringenin-chalcone synthase) compared with time courses for phytochrome-mediated end-product accumulation (anthocyanin, quercetin). AB - Time course for changes in the levels of enzymes characteristic of general phenylpropanoid metabolism (phenylalanine ammonia-lyase, PAL; EC 4.3.1.5) and of the flavonoid-glycoside branch pathway (naringenin-chalcone synthase, CHS; EC 2.3.1.74) were measured in the cotyledons of mustard (Sinapis alba L.) seedlings and compared with the rates of accumulation of related end products (anthocyanin and quercetin). Induction of enzyme levels and of end-product accumulation was carried out with red and far-red (FR) light, operating via phytochrome. The data are compatible with the concept that the phytochrome-mediated appearance of enzymes such as PAL and CHS is indeed a prerequisite for the appearance of anthocyanins and flavonols. However, there is no close correlation between enzyme levels and the rates of synthesis of end products which could justify the identification of specific rate-limiting enzymes. Rather, the data indicate that there is a second phytochrome-dependent step, beyond enzyme induction, where the actual rate of flavonoid accumulation is determined. Anthocyanin and quercetin accumulation respond differently to light. However, the relative action of continuous FR, red light pulses and 'stored phytochrome signal' is the same in both cases. This indicates that the mode of operation of phytochrome is the same in both cases. The two syntheses differ only in the degree of responsiveness towards phytochrome. The time course for changes in CHS levels in continuous FR, i.e. under conditions of phytochrome photosteady state, is similar to the time course for PAL levels whereas the time courses in darkness, following transfer from FR to darkness, are totally different. In the case of CHS, a transient rise is observed whereas, with PAL, an instantaneous drop in enzyme level occurs after transfer from FR to darkness. It is concluded that the 'stored phytochrome signal' operates in darkness in the case of CHS but not in the case of PAL. PMID- 24220868 TI - Polyclonal antibodies raised to phycocyanins contain components specific for the red-absorbing form of phytochrome. AB - Polyclonal antibodies raised in rabbits to a mixture of sodium-dodecyl-sulphate denatured C- and allo-phycocyanin, isolated from Anabaena cylindrica, cross-react with 124-kilodalton (kDa) phytochrome from etiolated oats, in enzyme-linked immunosorbent assays and on Western blots. The component(s) of the anti phycocyanin serum that cross-reacts with phytochrome appears to be specific for the red-absorbing form of phytochrome (Pr). These antibodies can be detached from Pr by irradiation with red light, and thus show photoreversible binding. This property has been used to immunopurify the anti-phytochrome component from the antiserum using red light as the eluting agent. Competition assays and epitope mapping studies indicate that the anti-phytochrome component may bind to a site located between 6 and 10 kDa from the amino-terminus of etiolated oat phytochrome. PMID- 24220869 TI - Control of wheat root growth. The effects of excision on growth, wall rheology and root anatomy. AB - Excision and subsequent incubation of the apices (1 cm) of wheat (Triticum aestivum L.) seedling roots in simple media severely reduced elongation from 28 mm.(24 h)(-1) in intact roots to a maximum of 2 mm.(24 h)(-1) in excised roots. The reduction in growth was accompanied by a loss of cell turgor in the growing zone but was correlated with a hardening of the cell walls in this region. Rheological properties were measured as percent extensibility (both plastic and elastic) using a tensiometer, and as instantaneous volumetric elastic modulus (epsilon i) using the pressure probe. Excision decreased plastic and elastic properties with a half-time of some 60 min. Plastic extension was reduced from 2.5% to 0.9% and elastic from 4.8% to 2.6% for an 8-g load. By contrast, epsilon i was increased by excision. The observed reduction in root elongation rate was accompained by a reduction in mature cell length from 240 MUm to 40 MUm and a shortening of the zone of cell expansion. PMID- 24220870 TI - Cell-type-specific expression of a wheat-germ agglutinin gene in embryos and young seedlings of Triticum aestivum. AB - We have investigated the levels of cell-specific expression of wheat-germ agglutinin (WGA) during the development of embryos and in 3-d-old seedlings. Southern blot analysis of genomic DNA derived from hexaploid and diploid wheat (Triticum) species indicates that the isolated cDNA (complementary DNA) clone is specific for isolectin B (WGA-B). Specific accumulation of transcript for WGA-B was determined by RNA blot analysis and in-situ hybridization. The WGA-B mRNA increased tenfold during embryogenesis between 10 and 40 d post-anthesis and then declined again as the seed reached maturity. The root tips of 3-d-old seedlings contained approximately threefold more WGA-B mRNA than mature seeds. In-situ hybridization experiments showed that during embryogenesis, WGA-B mRNA was present only in the epidermal layers of the radicle and the coleorhiza, while in 3-d-old seedlings it was found in the root-cap cells. To analyze de-novo transcription of WGA-B mRNA a new variation of in-situ hybridization was developed. RNAs from developing embryos and seedlings were labeled with [(3)H]uridine and then hybridized in-situ with unlabeled antisense and sense transcripts. These experiments demonstrated that accumulation of WGA-B mRNA in embryos and 3-d-old seedlings resulted, at least partially, from de-novo transcription. All cells containing WGA-B mRNA also contained WGA, as shown by immunocytochemistry. PMID- 24220871 TI - Regulation of photosynthetic electron-transport in Phaseolus vulgaris L., as determined by room-temperature chlorophyll a fluorescence. AB - The regulation of photosystem II (PSII) by light-, CO2-, and O2-dependent changes in the capacity for carbon metabolism was studied. Estimates of the rate of electron transport through PSII were made from gas-exchange data and from measurements of chlorophyll fluorescence. At subsaturating photon-flux density (PFD), the rate of electron transport was independent of O2 and CO2. Feedback on electron transport was observed under two conditions. At saturating PFD and low partial pressure of CO2, p(CO2), the rate of electron transport increased with p(CO2). However, at high p(CO2), switching from normal to low p(O2) did not affect the net rate of photosynthetic CO2 assimilation but the rate of electron transport decreased by an amount related to the change in the rate of photorespiration. We interpret these effects as 1) regulation of ribulose-1,5 bisphosphatecarboxylase (RuBPCase, EC 4.1.1.39) activity to match the rate of electron transport at limiting PFD, 2) regulation of electron-transport rate to match the rate of RuBPCase at low p(CO2), and 3) regulation of the electron transport rate to match the capacity for starch and sucrose synthesis at high p(CO2) and PFD. These studies provide evidence that PSII is regulated so that the capacity for electron transport is matched to the capacity for other processes required by photosynthesis, such as ribulose-bisphosphate carboxylation and starch and sucrose synthesis. We show that at least two mechanisms contribute to the regulation of PSII activity and that the relative engagement of these mechanisms varies with time following a step change in the capacity for ribulose bisphosphate carboxylation and starch and sucrose synthesis. Finally, we take advantage of the relatively slow activation of deactivated RuBPCase in vivo to show that the activation level of this enzyme can limit the rate of electron transport as evidenced by increased feedback on PSII following a step change in p(CO2). As RuBPCase as activated, the feedback on PSII declined. PMID- 24220872 TI - Attenuation of gamma-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to beta-cypermethrin. AB - The current study investigated the gamma-aminobutyric acid (GABA) levels and GABA metabolic enzymes (GABA transaminase (GABA(T)) and glutamate decarboxylase (GAD)) activities at 2 and 4 h after treatment, using a high-performance liquid chromatography with ultraviolet detectors and colorimetric assay, in the cerebral cortex of mice treated with 20, 40 or 80 mg/kg beta-cypermethrin by a single oral gavage, with corn oil as vehicle control. In addition, GABA protein (4 h after treatment), GABA(T) protein (2 h after treatment) and GABA receptors messenger RNA (mRNA) expression were detected by immunohistochemistry, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction, respectively. beta-Cypermethrin (80 mg/kg) significantly increased GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. Also, GABA immunohistochemistry results suggested that the number of positive granules was increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg beta-cypermethrin when compared with the control. Furthermore, the results also showed that GABA(T) activity detected was significantly decreased in the cerebral cortex of mice 2 h after beta-cypermethrin administration (40 or 80 mg/kg). No significant changes were found in GAD activity, or the expression of GABA(T) protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg beta-cypermethrin caused a significant decrease, compared with the vehicle control, in GABAA receptors mRNA expression 4 h after administration. These results suggested that attenuated GABA(T) activity induced by beta cypermethrin contributed to increased GABA levels in the mouse brain. The downregulated GABAA receptors mRNA expression is most likely a downstream event. PMID- 24220873 TI - Effects of 900 MHz electromagnetic field emitted by cellular phones on electrocardiograms of guinea pigs. AB - This study was carried out to determine the effects of electromagnetic field (EMF) emitted by cellular phones (CPs) on electrocardiograms (ECGs) of guinea pigs. A total of 30 healthy guinea pigs weighing 500-800 g were used. After 1 week of adaptation period, animals were randomly divided into two groups: control group (n = 10) and EMF-exposed group (n = 20). Control guinea pigs were housed in a separate room without exposing them to EMFs of CPs. Animals in second group were exposed to 890-915 MHz EMF (217 Hz of pulse rate, 2 W of maximum peak power and 0.95 wt kg(-1) of specific absorption rate) for 12 h day(-1) (11 h 45 min stand-by and 15 min speaking mode) for 30 days. ECGs of guinea pigs in both the groups were recorded by a direct writing electrocardiograph at the beginning and 10th, 20th and 30th days of the experiment. All ECGs were standardized at 1 mV = 10 mm and with a chart speed of 50 mm sec(-1). Leads I, II, III, lead augmented vector right (aVR), lead augmented vector left (aVL) and lead augmented vector foot (aVF) were recorded. The durations and amplitudes of waves on the trace were measured in lead II. The data were expressed as mean with SEM. It was found that 12 h day(-1) EMF exposure for 30 days did not have any significant effects on ECG findings of guinea pigs. However, this issue needed to be further investigated in a variety of perspectives, such as longer duration of exposure to be able to elucidate the effects of mobile phone-induced EMFs on cardiovascular functions. PMID- 24220874 TI - Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity. AB - The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg(-1)), while groups II-VII rats were pretreated with normal saline (10 ml kg(-1)), ascorbic acid (10 mg kg(-1)), nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg( 1)), and prednisolone (0.57 mg kg(-1)), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg(-1)) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg( 1)). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity. PMID- 24220875 TI - The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health. AB - The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection from telomere attrition associated with smoking. It is demonstrated in this work that both non-hydrolyzed carnosine and carcinine are characterized by greater bioavailability than pure l-carnosine subjected to enzymatic hydrolysis with carnosinase, and perform the detoxification of the alpha,beta-unsaturated carbonyl compounds present in tobacco smoke. We argue that while an array of factors has shaped the history of the 'safer' cigarette, it is the current understanding of the industry's past deceptions and continuing avoidance of the moral implications of the sale of products that cause the enormous suffering and death of millions that makes reconsideration of 'safer' cigarettes challenging. In contrast to this, the data presented in the article show that recommended oral forms of non-hydrolyzed carnosine and carcinine protect against CS-induced disease and inflammation, and synergistic agents with the actions of imidazole-containing dipeptide compounds in developed formulations may have therapeutic utility in inflammatory lung diseases where CS plays a role. PMID- 24220876 TI - The association between serum Dickkopf-1 levels and esophageal squamous cell carcinoma. AB - Serum Dickkopf-1(DKK-1) is elevated in many malignancies and is an important indicator of malignant potential. However, its significance in esophageal squamous cell cancer (ESCC) has not yet been clarified. We hypothesized a role for DKK-1 in patients with ESCC. The study consisted of 90 ESCC patients and 85 healthy controls. After diagnosis, the level of DKK-1 was measured in the serum samples by enzyme-linked immunosorbent assay and the levels of DKK-1 were much higher in the ESCC patients than in the healthy control group (p < 0.0001). For serum DKK-1, the sensitivity and specificity of the assay were 70 and 80%, respectively. The preoperative serum DKK-1 level was elevated in the ESCC patients. Although serum DKK-1 is not a specific biomarker for ESCC, it might be a useful marker for the diagnosis and treatment of ESCC. PMID- 24220877 TI - In vitro study on cytotoxicity and intracellular formaldehyde concentration changes after exposure to formaldehyde and its derivatives. AB - HeLa cells were exposed to formaldehyde and its metabolic derivatives, methanol, formic acid, and acetaldehyde, to investigate that the toxicity of formaldehyde is not caused by the chemical group. After 1 h of treatment with formaldehyde, mitochondrial assays showed that low concentrations (e.g. 10 MUmol/L) of formaldehyde promoted growth of the HeLa cells, while higher concentrations (e.g. >=62.5 MUmol/L) inhibited cell growth; while all four chemicals at a concentration of 125 MUmol/L affected cell growth, formaldehyde affected the largest. Reactive oxygen species concentration increased with the concentration of the exposure chemical. The endogenous formaldehyde content increased the most in the formaldehyde group, but in other three groups, it did not increase as the exposure concentration increased. Expression of dehydrogenase (formaldehyde dehydrogenase (FDH)) in the formaldehyde (10.40) and methanol (10.60) groups increased significantly compared with the control (1), while it was similar to the control in formic acid (0.90) and acetaldehyde (1.10) groups. Our results suggest that formaldehyde could affect cell activity and even enter cells. Exposure to formaldehyde changes the endogenous formaldehyde concentration in cells within 24 h, and this induces expression of FDH for formaldehyde degradation to maintain the formaldehyde balance. The toxicity of formaldehyde is not caused by the carbon atoms in the aldehyde, hydroxyl, or carboxyl groups. Formaldehyde is hypothesized to be an important signaling molecule in the regulation of cell growth and maintenance of the endogenous formaldehyde level. PMID- 24220878 TI - Rhabdomyolysis induced by excessive coffee drinking. AB - Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine containing products. PMID- 24220879 TI - Atypical outer retinal fluid accumulation in choroidal neovascularization: a novel OCT finding. AB - BACKGROUND AND OBJECTIVE: To report a novel optical coherence tomography (OCT) finding in choroidal neovascularization (CNV). PATIENTS AND METHODS: The authors identified seven eyes with CNV demonstrating the atypical pattern of fluid accumulation within the outer retina on OCT. Patient demographics, best corrected visual acuity and spectral-domain OCT (SD-OCT) images were collected for all available follow-up visits. Volume and area of the fluid were measured on SD-OCT. Microperimetry was performed in one case. RESULTS: The outer retinal fluid was located between the external limiting membrane (ELM) and the outer photoreceptor band on SD-OCT. Within this area, the outer segments of the photoreceptors were visualized as a continuous band, which appeared to split from the retina, dropping down toward the retinal pigment epithelium (mean area: 2.53 +/- 1.23 mm(2); mean volume: 0.19 +/- 0.20 mm(3)). All cases demonstrated the finding only at one time point during follow-up. Recovery of the outer retina and retinal function could be detected. CONCLUSION: Atypical intraretinal fluid accumulation externally to the ELM may be detected on SD-OCT in eyes with CNV. This finding may be transient and may not preclude subsequent improvement in visual function. The frequency of the presumed photoreceptor delamination and its full clinical significance remain to be defined. PMID- 24220880 TI - Optical coherence tomography in pediatric ophthalmology: current roles and future directions. AB - The application of existing optical coherence tomography (OCT) technology to the pediatric population is limited in both the design specification of the device and its hardware. However, the potential of OCT in the pediatric population has not been fully realized. The authors review the literature, highlighting the currently available spectral-domain OCT technology and summarizing the reported normal pediatric OCT parameters for retinal nerve fiber layer and macular thickness. They also review the pediatric ophthalmological conditions in which OCT has been used and discuss advancements in OCT design and their potential applications to the pediatric population. The use of OCT in pediatric populations is likely to increase greatly in the coming years, aiding clinical decision making and providing new insights into pediatric disease pathophysiology. PMID- 24220881 TI - Paracentral acute middle maculopathy and acute macular neuroretinopathy. AB - Type 1 acute macular neuroretinopathy (AMN), also known as paracentral acute middle maculopathy (PAMM), is a novel form of AMN in which spectral-domain optical coherence tomography (SD-OCT) demonstrates a characteristic hyper reflective band-like lesion at the level of the inner nuclear layer. This form of AMN has only recently been described in five patients who were predominantly older men with vasculopathy. Herein, we describe a young, healthy female patient with classic features of type 1 AMN or PAMM with SD-OCT. PMID- 24220882 TI - Enhanced depth imaging OCT and indocyanine green angiography changes in acute macular neuroretinopathy. AB - The authors describe indocyanine green angiography (ICGA) and enhanced depth imaging optical coherence tomography (EDI-OCT) in a 46-year-old male patient with acute macular neuroretinopathy (AMN). The chief complaint was decreasing visual acuity and metamorphopsia in both eyes of 1-month duration. Visual field assessment, fluorescein angiography, OCT, ICGA, and EDI-OCT were performed initially and at 3 months. ICGA showed choroidal vascular hyperpermeability and punctuate choroidal hyperfluorescent spots, especially in the left eye. EDI-OCT showed increased choroidal macular thickness, with inner and outer retinal layers affected. EDI-OCT and ICGA reveal that both the choroid and retina can be affected in AMN; however, the primary pathology and localization of depth of involvement in AMN remains unclear. PMID- 24220883 TI - Optical coherence tomography 2014. PMID- 24220884 TI - Enhanced visualization of the choroido-scleral interface using swept-source OCT. AB - An accurate analysis of the thickness and volume of choroid using optical coherence tomography (OCT) requires precise visualization of the choroido-scleral interface. Results of studies that use spectral-domain OCT (SD-OCT) to look at the percent visualization of the choroido-scleral interface for accurate analysis of choroidal thickness show varying success rates. This study assessed the visualization of choroido-scleral interface in 19 healthy participants (19 eyes) prospectively recruited for consecutive high-definition raster scanning with an SD-OCT system with and without enhanced depth imaging (EDI) and a prototype long wavelength swept-source OCT (SS-OCT) system. Choroido-scleral interface was visualized in all eyes imaged on SS-OCT, compared with 13 of 19 (68.4%) and 14 of 19 (73.6%) eyes imaged on SD-OCT without EDI (P = .009) and with EDI (P = .02), respectively. The prototype long-wavelength SS-OCT system, with its higher acquisition speed and deeper tissue penetration, may have better clinical utility in determining the involvement of choroid in various chorioretinal diseases. PMID- 24220885 TI - Comparison of retinal layer intensity profiles from different OCT devices. AB - BACKGROUND AND OBJECTIVE: The purpose of this study is to use automated multiple retinal layer segmentation to compare retinal layer intensity profiles between different spectral-domain optical coherence tomography (SD-OCT) devices with and without normalization. PATIENTS AND METHODS: A graph-based multistage segmentation approach was used to identify 11 boundaries in horizontal SD-OCT B scans passing through the foveal center. Four acquisition protocols from two different SD-OCT devices were applied on 34 eyes from 17 healthy participants. The mean intensity of the 11 layers was compared within each device and between the two devices. In addition, the intensity of the various layers was normalized against the vitreous and retinal pigment epithelium band, and the normalized intensity profiles were also compared. RESULTS: Within each OCT device, the mean intensity of the 11 retinal layers did not show significant difference (P values of paired t test ranging between 0.15 and 0.30). For the two different devices, before normalization, the mean intensity of the 11 retinal layers differed significantly (P = .02 to .03). After normalization, the mean intensity no longer differed significantly (P = .26 to .51). Linear regression demonstrated an average R(2) of 0.94 (P < .001) before normalization and 0.98 (P < .001) after normalization between the two devices. CONCLUSION: The morphology of the intensity profiles was found to be similar within each SD-OCT device. Comparing intensity profiles from the two different devices, significant differences in unnormalized layer intensity were observed. Following normalization, the differences between OCT devices were no longer significant. PMID- 24220887 TI - Cytogenetics of four telotrisomics in barley (Hordeum vulgare L.). AB - Four barley telotrisomics (Triplo 3S, 5S, 6S, and 7S) were studied. No major qualitative differences in morphology between the telotrisomics and their diploid sibs were found. The pollen and seed fertility of these telotrisomics was comparable to their diploid sibs. The meiotic study showed that the average frequency of 6II + 1III at diakinesis and metaphase I was 84.2% and 71.7%, respectively. The normal chromosome separation ranged from 77.2% to 89.4% at anaphase I through telophase II. The transmission rate of the extra telocentric chromosomes averaged 28.4% upon selfing and 28.7% through the female. All four telotrisomics showed various degrees of pollen transmission, the average being 3.6%. Ditelotetrasomic plants (2n = 14 + 2 homologous telocentrics) were obtained in the progenies of selfed monotelotrisomic plants of all four types. These ditelotetrasomic plants were viable and showed various degrees of seed fertility. PMID- 24220886 TI - High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina. AB - Alterations of cholesterol metabolism are responsible for vasospastic angina and atherosclerosis. To comprehensively evaluate cholesterol metabolism, 18 sterols, including cholesterol, 6 cholesteryl esters (CEs), 3 cholesterol precursors, and 8 hydroxycholesterols (OHCs), were simultaneously analyzed using hybrid solid phase extraction (SPE) purification coupled to high-temperature gas chromatography-mass spectrometry (HTGC-MS). Methanol-based hybrid SPE increased the selective extraction, and HTGC resulted in a good chromatographic resolution for the separation of lipophilic compounds. The limits of quantification of cholesterol and CEs ranged from 0.2 to 10.0 MUg/ml, while OHCs and cholesterol precursors ranged from 0.01 to 0.10 MUg/ml. Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r2 > 0.98). The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively. The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%. The cholesterol signatures showed sex differences in patients with vasospastic angina and may associate with 24-reductases. This technique can be useful for making clinical diagnoses and for an increased understanding of the pathophysiology of vasospastic angina. PMID- 24220888 TI - Full and reduced models for yield trials. AB - Empirical results routinely demonstrate that the reduced Additive Main effects and Multiplicative Interaction (AMMI) model achieves better predictive accuracy for yield trials than does the full treatment means model. It may seem mysterious that treatment means are not the most accurate estimates, but rather that the AMMI model is often more accurate than its data. The statistical explanation involves the Stein effect, whereby a small sacrifice in bias can produce a large gain in accuracy. The corresponding agricultural explanation is somewhat complex, beginning with a yield trial's design and ending with its research purposes and applications. In essence, AMMI selectively recovers pattern related to the treatment design in its model, while selectively relegating noise related to the experimental design in its discarded residual. For estimating the yield of a particular genotype in a particular environment, the AMMI model uses the entire yield trial, rather than only the several replications of this particular trial, as in the treatment means model. This use of more information is the source of AMMI's gain in accuracy. PMID- 24220889 TI - Allelism of Endosperm Balance Number (EBN) in Mexican tuber-bearing Solanum species. AB - Endosperm Balance Number (EBN) is a genetic, dose-dependent crossability system functioning in tuber-bearing Solanum species. Each species has been assigned 1EBN, 2EBN, or 4EBN. Species thus designated cross only within their EBN group. Doubling of chromosome number also doubles the EBN. The ploidy: EBN ratio is not consistent among Solanum species. Some diploids are 2EBN while others are 1EBN. Some tetraploids are 4EBN while others are 2EBN. Species from Mexico typically have EBNs that are one-half of their ploidy [e.g. 2x(1EBN), 4x(2EBN)]. Hybrids of Mexican species and a South American species, 2x(1EBN) S. Commersonii, and its 4x(2EBN) colchicine derivative were made and crossed to 1, 2, and 4EBN standard testers to determine the relationship of the genetic organization of EBN among and within these species. Diploid hybrids crossed only to 1EBN standard testers. Hybrids of 4x(2EBN) S. commersonii and 4x(2EBN) Mexican species crossed almost exclusively to 2EBN standard testers. Complex tetraploid hybrids involving S. commersonii, S. stenophyllidium (a Mexican diploid), and Mexican tetraploids of series Longipedicellata also crossed only to 2EBN testers. The apparent lack of recombination and segregation for EBN in these hybrids indicates that the genomes of the Mexican diploid and tetraploid species carry EBN in a way genetically similar to that of the South American species S. Commersonii. PMID- 24220890 TI - Genetic characterization of a double-flowered tobacco plant obtained in a transformation experiment. AB - A leaf-disk transformation experiment was performed with tobacco (Nicotiana tabacum L.) using a binary vector and a strain of Agrobacterium tumefaciens that carried a wild-type Ti-plasmid, pTiBo542. Although the majority of kanamycin resistant, transgenic plants was morphologically normal, one of the plants was double-flowered and had a slightly wavy stem and leaves whose edges were bent slightly upwards. The abnormal morphology was controlled by a single, dominant Mendelian gene. Young plants that carried this gene were distinguishable from normal plants at the stage of cotyledons. The homozygotes, with respect to this gene, were more seriously deformed than the heterozygotes. DNA segments derived from the binary vector and from the TL-and TR-DNA of pTiBo542 were detected in the double-flowered plant, but the T-DNA genes involved in biosynthesis of phytohormones were absent from the plant. The abnormal morphology, the resistance to kanamycin, and the segments of foreign DNA were genetically linked, and the linkage was very tight, at least between the abnormal morphology and the resistance to kanamycin; the meiotic recombination frequency was less than 0.02%, if recombination occurred at all. PMID- 24220891 TI - The ms1 mutation in soybean: involvement of gametes in crosses with tetraploid soybean. AB - Previous studies indicated that ms1ms1 malesterile female-fertile soybean (Glycine max [L.] Merr.) plants can produce seeds with different ploidy levels. The codominant chlorophyll-deficient mutant y11 was used in attempts to understand the embryo-endosperm relationship in seed production in ms1ms1 plants and to determine the mechanism of gamete formation in the ms1 mutation. Crosses were conducted between yellow-green male-sterile plants (ms1ms1Y11y11) and green fertile tetraploid cultivars (Ms1Ms1Ms1Ms1Y11Y11Y11Y11) in the greenhouse in the summers of 1987 and 1988. A total of 2,007 cross-pollinations were made. Thirty hybrid seeds were obtained, and plants were analyzed for chromosome number, fertility, and color. All the hybrid seedlings were tetraploid and fertile. No triploids were found. Among the 30 F1 plants, 7 were green (Y11Y11Y11Y11), 17 were green-yellow (Y11Y11Y11y11), and 6 were yellow-green (Y11Y11y11y11). The segregation ratio was close to the expected 1 green: 2 green-yellow: 1 yellow green (X(2) = 0.38; 0.90>p>0.75). From the results of this experiment, we conclude that: (1) triploids were not produced by crossing diploid ms1ms1 soybean plants with tetraploid plants; (2) tetraploid progeny can be produced from these crosses by the fusion of 2n ms1 eggs, or fusion of other 2n gametophyte cells in the embryo sac with a 2x sperm from tetraploid plants; (3) the megaspore mother cell of male-sterile plants undergoes meiotic division without cytokinesis after telophase II and forms more than the normal number of gametes, which can fuse with each other to generate tetraploid gametophyte cells. PMID- 24220892 TI - Cytogenetic analysis of three genetic sexing strains of Ceratitits capitata. AB - Polytene chromosomes of three genetic sexing strains of Ceratitis capitata were analyzed. The genetic sexing mechanism is based on a pupal color dimorphism (white-brown) and is the result of a reciprocal translocation between the Y chromosome and the autosome bearing the w locus (white pupal case). The analyzed polytene chromosomes were derived from two different pupal tissues, the orbital bristle and fat body cells. The Y chromosome is visible in both tissues, while the autosomes present a different banding pattern. Based on these features, the autosome breakpoints in the three Y; autosome translocations were mapped, and the homology of the translocated autosome in both tissues was established. In addition, the location of the break-points was compared to the stability of these three strains. PMID- 24220893 TI - Two-step one-dimensional SDS-PAGE analysis of LMW subunits of glutelin : 2. Genetic control of the subunits in species related to wheat. AB - Analysis of intergeneric substitution lines in hexaploid wheats by a two-step electrophoretic method of protein separation revealed that low-molecular-weight (LMW) subunits of glutelin in Triticum longissimum, T. Umbelullatum, Elytrigia elongata (2 x) were controlled by chromosomes/chromosome arms 1S (l) , 1U, and 1ES, respectively. A LMW glutelin band in Secale montanum was detected but its chromosomal location could not be determined. Genes controlling gliadins and HMW subunits of glutelin were also located on chromosome 1S (l) in T. longissimum. PMID- 24220894 TI - Evidence of simple genetic control in potato of ability to restrict potato leaf roll virus concentration in leaves. AB - The concentration of potato leaf roll virus (PLRV), measured by quantitative enzyme-linked immunosorbent assay, in foliage of plants of cv Maris Piper and clone G7445(1) with secondary infection was 2,700 ng/g leaf and 120 ng/g leaf, respectively. In experiments to examine the genetic control of their ability to restrict the multiplication of PLRV, reciprocal crosses were made between these two clones. Among 40 genotypes from the progeny of the crosses, about half had a low PLRV concentration in plants with secondary infection and the other half had a high concentration. The possibility of monogenic control of the character that restricts PLRV multiplication in such clones of Solanum tuberosum is discussed. PMID- 24220895 TI - Characterization of responses to temperature and photoperiod for time to flowering in a world lentil collection. AB - The times from sowing to first flowering (f) of 231 accessions of lentil (Lens culinaris Medik.), comprising germ plasm from eight countries and breeding lines from ICARDA in Syria, were recorded in four glasshouse environments; two photoperiods (16 and 13 h/day) combined with warmer (24 degrees /13 degrees C) and cooler (18 degrees /9 degrees C) day/night temperatures. The linear model 1/f=a+bT + cP (where T is mean diurnal temperature and P is photoperiod) provided an average fit over the 231 accessions of r (2)=0.852. Since there is no interaction term in this linear model, the flowering responses of an accession to temperature and photoperiod are independent. The values of the constants b and c indicate relative responsiveness of rate of progress towards flowering (1/f) to temperature and photoperiod, respectively. Comparison among the 231 accessions showed a weak, but significant, negative correlation between the values of b and c (r=-0.291, P<0.01). Since the proportion of the variance of b not attributed to its linear regression on c was >0.91, we conclude that these phenological responses are under separate control and that there is considerable scope for selection of any combination of sensitivities to temperature and photoperiod in lentil. Just as a large proportion of the variation among accessions in mean time to first flowering was attributed to country of origin, so also was variability in the values of the constants a, b, and c. In particular, sensitivity to photoperiod (i.e., the value of constant c) was dependent upon latitude of origin. Breeding lines from ICARDA were equally variable in a, b, and c as were germ plasm accessions from elsewhere, while the mean values were similar to those of accessions from neighboring Jordan. A single accession of wild lentil (L. culinaris subsp. orientalis) from Turkey showed flowering responses to T and P similar to the mean value of accessions of cultivated lentil from that country. Results from diverse environments for the Argentinian cv Precoz show that the use of this linear model facilitates predictions of time to flowering in any environment (within wide limits) of known mean temperature and photoperiod. The model, then, minimizes the need for multisite evaluations of phenology, since predictions of pre-flowering duration in any environment, and characterization of flowering responses to photoperiod and temperature, can now be achieved by screening germ plasm in a few, carefully selected locations. PMID- 24220896 TI - Transfer of germ plasm from the secondary to the primary gene pool in pennisetum. AB - Germ plasm from the A'-genome of Pennisetum purpureum Schum. (A'A'BB) of the secondary gene pool was transferred to cultivated pearl millet (AA) [P. glaucum (L.) R. Br.] by pollinating cytoplasmicnuclear male-sterile (cms) pearl millet with fertile allohexaploid pearl millet x P. purpureum hybrids (AAA'A'BB). Certain allohexaploids used as pollinators on cms pearl millet resulted in 14 chromosome diploid pearl millet progenies. Three types of diploid pearl millet plants were produced in addition to the expected 28-chromosome AAA'B-genome plants: (1) cms plants with only the A-genome, (2) cms plants with the A- and A' genomes, and (3) fertile plants with the A- and A'-genomes. The latter group has allowed the utilization of genes for fertility restoration, stiff stalk, maturity, height, and morphological characteristics from the A'-genome of P. purpureum in the pearl millet breeding program. Production of monoploid gametes by the allohexaploids appeared to be genetically controlled. PMID- 24220897 TI - Marker-based mapping of quantitative trait loci using replicated progenies. AB - When heritability of the trait under investigation is low, replicated progenies can bring about a major reduction in the number of individuals that need to be scored for marker genotype in determining linkage between marker loci and quantitative trait loci (QTL). Savings are greatest when heritability of the trait is low, but are much reduced when heritability of the quantitative trait is moderate to high. Required numbers for recombinant inbred lines will be greater than those required for a simple F2 population when heritabilities are moderate to high and the proportion of recombination between marker locus and quantitative trait locus is substantial. PMID- 24220898 TI - Chloroplast DNA diversity in wild and cultivated species of rice (Genus Oryza, section Oryza). Cladistic-mutation and genetic-distance analysis. AB - Using a novel nonaqueous procedure, chloroplast DNA was isolated from 318 individual adult rice plants, representing 247 accessions and the breadth of the diversity in section Oryza of genus Oryza. Among them, 32 different cpDNA restriction patterns were distinguished using the restriction endonucleases EcoRI and AvaI, and they were further characterized by restriction with BamHI, HindIII, SmaI, PstI, and BstEII enzymes. The differences in the electrophoretic band patterns were parsimoniously interpreted as being the result of 110 mutations, including 47 restriction site mutations. The relationships between band patterns were studied by a cladistic analysis based on shared mutations and by the computation of genetic distances based on shared bands. The deduced relationships were compared with earlier taxonomical studies. The maternal parents for BC genome allotetraploids were deduced. Within species, cpDNA diversity was found larger in those species with an evolutionary history of recent introgression and/or allotetraploidization. Occasional paternal inheritance and recombination of cpDNA in rice was suggested. PMID- 24220899 TI - Nonparametric approach to multitrait selection for yield in groundnut (Arachis hypogaea L.). AB - Eight characters related to nitrogen fixation and pod development measured 30 days after flowering were evaluated for their correct grading of the relative yield performance of 17 genetically diverse lines of groundnut (Arachis hypogaea L.). Each line was assigned a high or low yield status based on its pod yield, shelling percentage, and 100-kernel weight. Seventeen character combinations were examined for their relative merit in correct identification of the yield status of lines. The character sets, nitrogenase activity alone or in combination with nitrogen percent or shoot weight identified the status of 77% of lines correctly. The extent to which various characters accounted for the variation in pod yield was also checked by multiple regression analysis. While the character combination, nitrogen percent plus leaf area explained 75% of variation in pod yield, nodule mass, nitrogenase activity, and leaf area occurred in some other combinations that explained yield variation to a lesser extent. These analyses point to the profitability of involving crop physiological traits such as leaf area and nitrogen percent in selecting for relative yield performance in groundnut. PMID- 24220900 TI - The improbability of irradiated spermatozoa as gene transfer vectors in chickens. AB - It is concluded that chromatin fragments derived from irradiated chicken spermatozoa are not viable vectors for gene transfer. In three experiments conducted at sequential intervals over a period of 1 1/2 years, no marker traits were found in 1,065 G0 progeny from irradiated spermatozoa of Minnesota Dominant Marker males inseminated into recessive Rhode Island Red and White Leghorn females. The inability to secure transformants is ascribed to the following factors: a maximum of five and probably fewer potential vector fragments for each G0 progeny because of irradiation effect on spermatozoan ability to enter the germinal disc; uncertainty of DNA integrity from highly irradiated chromatin; no known mechanism for release of chromatin fragments from irradiated spermatozoa supernumerary pronuclei; and the uncertainty of selective integration into the zygotic nucleus. PMID- 24220901 TI - Mutants of Arabidopsis with alterations in seed lipid fatty acid composition. AB - A diverse collection of mutants of Arabidopsis with altered seed lipid compositions was isolated by determining the fatty acid composition of samples of seed from 3,000 mutagenized lines. A series of mutations was identified that caused deficiencies in the elongation of 18?1 to 20?1, desaturation of 18?1 to 18?2, and desaturation of 18?2 to 18?3. In each of these cases the wild type exhibited incomplete dominance over the mutant allele. These results, along with results from earlier studies, point to a major influence of gene dosage in determining the fatty acid composition of seed lipids. A mutation was also isolated that resulted in increased accumulation of 18?3. On the basis of the effects on fatty acid composition, the nature of the biochemical lesion in three of the mutants could be tentatively attributed to deficiencies in activities of specific enzymes. The other mutant classes had relatively less pronounced changes in fatty acid composition. These mutants may represent alterations in genes that regulate lipid metabolism or seed development. The availability of the mutants should provide new opportunities to investigate the mechanisms that control seed lipid fatty acid composition. PMID- 24220902 TI - Isolation of EMS-induced mutants in Arabidopsis altered in seed fatty acid composition. AB - Mutants of Arabidopsis thaliana were identified by screening pedigreed M3 seed collections from EMS-treated plants for changes in fatty acid (FA) composition. The FA phenotypes of the most dramatic mutants are as follows: G30 and 1E5 (allelic) lack linolenic acid (18?3) and are elevated in linoleic acid (18?2); 4A5 is deficient in 18?2 and 18?3 and fourfold increased in oleic acid (18?1); 9A1 lacks all FAs > C18 and is twofold increased in 18?1; 1A9 is twofold increased in palmitic acid (16?0) and decreased by one-half in 18?1; 2A11 is two to threefold increased in stearic acid (18?0) and decreased by one-half in 18?1. Based on segregation of F2 selfed plants derived from crosses to wild type, all of these phenotypes are the result of single gene mutations. PMID- 24220903 TI - Production of transgenic pea (Pisum sativum L.) plants by Agrobacterium tumefaciens - mediated gene transfer. AB - A transformation system that allows regeneration of transgenic pea plants from calli selected for antibiotic resistance was developed. Explants from axenic shoot cultures and seedling epicotyls were cocultivated with nononcogenic Agrobacterium tumefaciens strains, and transformed callus could be selected on callus-inducing media containing either 15 mg/l hygromycin or 75 mg/l kanamycin. After several passages on regeneration medium, shoot organogenesis could be reproducibly induced on hygromycin-resistant calli, but not on the calli selected for kanamycin resistance. Regenerated shoots could subsequently be rooted and transferred into the greenhouse. In addition, the effects of different callus inducing and growth media on organogenesis were investigated. The transformation of the calli and regenerated plants was confirmed by DNA analysis. PMID- 24220904 TI - Intraspecific diversity of sugar beet (Beta vulgaris) mitochondrial DNA. AB - Mitochondrial (mt) DNA, isolated from different sugar beet populations, was analyzed using BamHI and EcoRI restriction enzymes. It was shown that plants possessing the new mtDNA types are revealed among O-type fertilizers quite frequently. Among cytoplasmic male sterile (cms) plants, which evolved during cultivation of O-type fertilizers, plants with altered mt genome were found. PMID- 24220905 TI - Additive inheritance of resistance to pod rot caused by Phytophthora palmivora in cocoa. AB - Quantitative inheritance of resistance to Phytophthora pod rot (Ppr) was studied in cocoa hybrid progeny from 12 Trinitario x Amazonian crosses and their reciprocal crosses. The crossing scheme was similar to a factorial design. Disease was assessed by the number and percentage of infected pods on each tree. Highly significant differences due to general combining abilities (GCA) were obtained for all characters, except for the GCA of Trinitario on total pod production. Differences for specific combining ability (SCA) were not significant for all characters. There were no significant differences between reciprocal crosses. The Trinitario clone K82 provided the only source for the hybrid progenies of strong Ppr resistance to the hybrid progenies, while K20 provided moderate resistance. Other parental clones - KA2-101, KA5-201, KEE 2, KEE 5, and KEE 52 - produced progenies which were susceptible to Ppr. It is evident that resistance to Ppr in cocoa is inherited additively. Maternal and cytoplasmic effects were assumed to have no influence on inheritance of resistance. It is also concluded that resistance to Ppr of the kind shown by K82 is likely to be horizontal resistance. Breeding for high-yielding cultivars combined with Ppr resistance is the most effective way of controlling Ppr of cocoa on the crops of growers with small holdings in Papua New Guinea. PMID- 24220906 TI - High resolution bands in maize chromosomes by G-banding methods. AB - It was demonstrated that G-bands are unequivocally present in plant chromosomes, in contrast to what had been formerly believed by plant cytologists. Maize chromosomes prepared by an enzymatic maceration method and treated with trypsin or SDS showed clear G-bands spreading along the chromosomes. The most critical point during the G-banding procedures was the post-fixation with glutaraldehyde solution. Banding patterns were processed by using the chromosome image analyzing system and a clearer image was obtained. Gbanding technique and the image manipulation method described here can be applied to many plant species, and would contribute new information in the field of plant cytology and genetics. PMID- 24220907 TI - Relationship of restriction fragment length polymorphisms to single-cross hybrid performance of maize. AB - Isozymes and restriction fragment length polymorphisms (RFLPs) have been proposed for use in varietal identification and selection for agronomic traits. Although the use of isozymes for these purposes has been well documented, evaluation of the efficacy of RFLP technology as applied to crop improvement is far from complete. This investigation was conducted to study the relationship between RFLP derived genotypes and heterotic patterns of a group of maize (Zea mays L.) inbred lines. A total of 22 inbreds was crossed to four testers (B73, B76, Mo17, and Va26) in combinations that minimized crossing within heterotic groups. Forty seven single-cross progeny were subsequently evaluated for several agronomic traits (including grain yield and moisture, ear height, and root lodging) over 2 4 consecutive years at two to four Iowa locations in a randomized complete-block design. The inbred lines were subjected to RFLP analysis, which involved 47 genomic clones and the restriction enzymes EcoRI and HindIII. Hybrid RFLP patterns were predicted from their inbred parents. Modified Roger's distances were computed to estimate genetic distance among the inbred lines. Principal component analysis facilitated ascertainment of relative dispersion of the inbreds based on the frequency of variants at specific RFLP loci. Evident associations of variants with genes affecting agronomic traits were identified by principal component regression analysis, in which adjusted hybrid means were regressed on the matrix of hybrid variants frequencies. The hybrid means were adjusted by removing environmental effects, using residuals as dependent variables in the regression analysis. Results from this study suggest that RFLP analysis may be of value in allocating maize inbreds to heterotic groups, but no relationship between RFLP-based genetic distance and hybrid performance was apparent. Principal component regression identified variants potentially linked to genes that control specific agronomic traits. PMID- 24220908 TI - Dosage effects of chromosomes of homoeologous groups 1 and 6 upon bread-making quality in hexaploid wheat. AB - The endosperm storage proteins, glutenin and gliadin, are major determinants of bread-making quality in hexaploid wheat. Genes encoding them are located on chromosomes of homoeologous groups 1 and 6. Aneuploid lines of these groups in spring wheat cultivar 'Chinese Spring' have been used to investigate the effect of varying the dosage of chromosomes and chromosome arms upon bread-making quality, where quality has been assessed using the SDS-sedimentation test. Differences between the group 1 chromosomes for quality were greater than those between the group 6 chromosomes. The chromosomes were ranked within homoeologous groups for their effect on quality as follows (>=better quality): 1D>1B>1A and 6A>6B=6D. The relationship of chromosome dosage with quality was principally linear for four of the chromosomes, but not for 6B and 6D. Increases in the dosage of 1B, 6A and, especially, 1D, were associated with significant improvements in quality, whereas increases in the dosage of 1A were associated with reductions in quality. The effects of 1A and 1D were such that the best genotype for quality was nullisomic 1A-tetrasomic 1D. For group 1, effects of the long arm appeared in general to be more important than effects of the short arm. For group 6, effects were found associated with the long arms as well as with the short arms, a surprising result in view of the absence of genes encoding storage proteins on the long arms. Significant interactions were found between chromosomes and genetic backgrounds, and between individual chromosomes. Analysis of trials grown over two years demonstrated that, although additive environmental differences over years and genotype x years interaction were present, they were relatively small in magnitude compared with purely genetic differences. PMID- 24220909 TI - Plasma alkylresorcinol metabolites as biomarkers for whole-grain intake and their association with prostate cancer: a Swedish nested case-control study. AB - BACKGROUND: Observational studies have mostly found no association between self reported whole-grain intake and prostate cancer. Plasma alkylresorcinol metabolites have been suggested as biomarkers for whole-grain intake in free living populations. METHODS: We investigated the major dietary and lifestyle determinants of plasma alkylresorcinol metabolites in a nested case-control study (1,016 cases and 1,817 controls) in the Malmo Diet and Cancer Study. Multivariate adjusted ORs and 95% confidence intervals (95% CI) were estimated to assess the association between plasma alkylresorcinol metabolites and prostate cancer using logistic regression. RESULTS: Whole-grain intake, waist circumference, educational level, and smoking status were the main determinants of alkylresorcinol metabolites. We observed significant correlations between alkylresorcinol metabolites and whole-grain (r = 0.31) and fiber (r = 0.27) intake. Metabolite concentration was positively associated with prostate cancer risk (Poverall effect = 0.0004) but the association was not linear (P = 0.04). The lowest risk was seen among men with moderate plasma concentrations. The OR for high compared with moderate plasma alkylresorcinol metabolites was 1.41 (95% CI, 1.10-1.80) for prostate cancer. CONCLUSIONS: Results suggest that plasma alkylresorcinol metabolites are mainly determined by whole-grain intake in this nested case-control study of Swedish men. The increased risk of prostate cancer seen among men with high plasma alkylresorcinol metabolites requires further study, but residual confounding, detection bias, or competing risks of nonprostate cancer-related deaths are plausible explanations that could not be ruled out. IMPACT: We found no evidence of a protective effect of whole grains on incident prostate cancer. Further validation of alkylresorcinol metabolites as a biomarker for whole-grain intake is needed. PMID- 24220910 TI - A genome-wide association study of renal cell carcinoma among African Americans. AB - Genome-wide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AA), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNP) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases and 543 controls). The 12p11.23 variant rs10771279, located 77 kb from the European ancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P = 1.2 * 10(-7)) but did not replicate (P = 0.99). Consistent with European-ancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [OR, 0.76, 95% confidence interval (CI), 0.64-0.91; P = 0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07, respectively, among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR, 0.56; P = 7.4 * 10(-7)) and absent for cases of other or unknown histology (OR, 1.02; P = 0.86). Analyses of rs7105934 by subtype among European-ancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92, respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to clear-cell RCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed. PMID- 24220911 TI - The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. AB - BACKGROUND: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers. METHODS: A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses. RESULTS: The final model involving gender, age, AFP-L3, alpha fetoprotein (AFP), and des carboxy-prothrombin ("GALAD") was developed in a "discovery" data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage. CONCLUSIONS: The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches. IMPACT: Our data provide evidence that an entirely objective serum biomarker-based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches. PMID- 24220912 TI - Serum levels of cytokines and biomarkers for inflammation and immune activation, and HIV-associated non-Hodgkin B-cell lymphoma risk. AB - BACKGROUND: HIV infection is associated with a marked increase in risk for non Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. METHODS: In this study, serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1 to 5 years preceding AIDS NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV(+) controls from the Multicenter AIDS Cohort Study (MACS). RESULTS: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), interleukin (IL)-6, IL-10, IP 10/CXCL10, neopterin, and TNF-alpha were elevated in those HIV(+) individuals who went on to develop AIDS-NHL. In addition, the fraction of specimens with detectable IL-2 was increased and the fraction with detectable IL-4 was decreased in these subjects. CONCLUSIONS: These results suggest that long-term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV(+) individuals. IMPACT: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF-alpha may serve as biomarkers for AIDS-NHL. . PMID- 24220913 TI - Postdiagnosis C-reactive protein and breast cancer survivorship: findings from the WHEL study. AB - BACKGROUND: Serum C-reactive protein (CRP) is a marker of acute inflammatory response and has been associated with health outcomes in some studies. Inflammation and immune response may have potential prognostic implications for breast cancer survivors. METHODS: The Women's Healthy Eating and Living Study includes 2,919 early-stage breast cancer survivors with serum collected 2 years postdiagnosis and follow-up for clinical outcomes over approximately 7 years. CRP concentrations were measured using high-sensitivity electrochemiluminescence assay. Outcomes, including all-cause mortality, breast cancer-specific mortality, and additional breast cancer events were oncologist verified from medical records and death certificates. Cox proportional hazards models were conducted with adjustment for potential confounding factors to generate HRs and 95% confidence intervals (CI). RESULTS: CRP concentrations in women diagnosed with breast cancer were associated with death due to any cause, death due to breast cancer, and additional breast cancer events, after adjustment for sociodemographic and cancer characteristics (lnCRP: P < 0.05 for all three outcomes). The HR for women with (vs. without) acute inflammation suggests a threshold effect on overall survival, rather than a dose-response relationship (>= 10.0 mg/L vs. <1 mg/L: HR, 1.96; 95% CI, 1.22-3.13). Associations were similar for breast cancer-specific mortality (HR, 1.91; 95% CI, 1.13-3.23) and any additional breast cancer-related event (HR, 1.69; 95% CI, 1.17-2.43). CONCLUSIONS: Acute inflammation status (CRP >= 10 mg/L) may be an important independent biomarker for long-term survival in breast cancer survivors. IMPACT: Interventions to decrease circulating CRP concentrations in breast cancer survivors with acute inflammation may improve prognosis. PMID- 24220914 TI - Psychological distress after a positive fecal occult blood test result among members of an integrated healthcare delivery system. AB - BACKGROUND: Colorectal cancer screening (CRCS) reduces morbidity and mortality; however, the positive benefits might be partially offset by long-term distress following positive screening results. We examined relationships among colorectal cancer-specific worry and situational anxiety after positive fecal occult blood tests [FOBT (+)] compared with receipt of negative results. METHODS: Of note, 2,260 eligible members of Group Health, an integrated healthcare delivery system, completed baseline surveys and received FOBT screening kits, with 1,467 members returning the kits. We matched FOBT (+) patients (n = 55) 1:2 on age and sex with FOBT (-) respondents (n = 110). Both groups completed follow-up surveys at 7 to 14 days and 4 months after screening. We assessed situational anxiety (State Trait Anxiety Inventory, STAI), colorectal cancer worry frequency, and mood disturbance. RESULTS: Mean age was 59 years, and majority were women (62%) and White (89%). After adjusting for age, sex, and baseline worry, at 7 to 14 days after screening, the FOBT (+) group was 3.82 [95% confidence interval (CI), 1.09 13.43] times more likely to report colorectal cancer-related mood disturbances and significantly higher mean STAI scores than the FOBT (-) group (mean = 38.8 vs. 30.9; P = 0.007). At 4-month posttest, mood disturbances and situational anxiety seemed to drop to baseline levels for FOBT (+). No colon cancer worry frequency was observed. CONCLUSIONS: FOBT (+) results are associated with short term situational anxiety and colorectal cancer-specific mood disturbances. IMPACT: Distress from FOBT (+) results declined to near-baseline levels by 4 months. Additional studies are needed to clarify the relationship between long term distress and follow-up colonoscopy. PMID- 24220916 TI - Enhanced hypoosmoregulatory response to growth hormone after cortisol treatment in immature rainbow trout, Salmo gairdneri. AB - The growth-independent effect of ovine growth hormone (oGH) and oGH + cortisol treatment on seawater (SW) adaptation in immature rainbow trout, Salmo gairdneri was investigated. Fish were injected every second day with saline, 2.0 MUg oGH/g or 2.0 MUg oGH + 8.0 MUg cortisol/g for a maximum of 8 injections in freshwater (FW). Subgroups were transferred to 280/00 SW after 4 or 8 injections, and changes in plasma Na(+) and Cl(-), muscle water content and gill Na(+)/K(+) ATPase activity were measured. In both of the hormone-treated groups retained in FW, gill Na(+)/K(+)-ATPase activity and interlamellar chloride cell density increased. The effects were most pronounced in the oGH + cortisol group after 2 weeks of treatment. After transfer to SW most of the control fish died due to the osmotic stress, whereas in the hormone-treated groups, mortality was low and there was a positive correlation between pretransfer gill Na(+)/K(+)-ATPase and the ability to maintain ionic-osmotic homeostasis after SW transfer. After two weeks of oGH + cortisol treatment, gill Na(+)/K(+)-ATPase activity was maximal. In contrast, after SW transfer, Na(+)/K(+)-ATPase activity increased further in the oGH-treated group. This group regulated ionic-osmotic parameters less effectively than the oGH + cortisol-treated group. The data indicate that GH and cortisol are important hormones in the regulation of hypoosmoregulatory mechanisms in S. gairdneri. PMID- 24220917 TI - Determination of 3,5,3'-triiodo-L-thyronine (T3) levels in tissues of rainbow trout (Salmo gairdneri) and the effect of low ambient pH and aluminum. AB - Tissue T3 (3,5,3'-triiodo-L-thyronine) concentrations were measured in rainbow trout, Salmo gairdneri, after digestion by Pronase or collagenase and extraction with ethanolic ammonia (99:1, v/v) followed by 2N NH4OH and chloroform. Recoveries of [(125)I]T3 administered in vivo or in vitro were high and consistent and there was close parallelism between sample dilutions and the radioimmunoassay curve, but recoveries of unlabeled T3 administered in vitro were low and variable. Alternatively, trout were brought to isotopic equilibrium by [(125)I]T3 infusion for 96 h, the extracted [(125)I]T3 determined by gel filtration and the tissue T3 content calculated from the specific activity of plasma [(125)I]T3. By the latter method, tissue T3 concentrations were: intestine (4.2 ng/g), kidney (2.5), liver (2.8), stomach (1.5), heart (1.0), muscle (0.7), gill (0.6) and skin (0.3). Muscle (67% of body weight) comprised the largest tissue T3 pool (82% of all tissues examined). Seven days exposure of trout to water acidified with H2SO4 (pH 4.8) or acidified water containing aluminum (21.6 mM), decreased tissue T3 content generally and particularly in muscle (14% of controls). In conclusion, skeletal muscle is the largest T3 tissue pool and seems highly responsive to altered physiologic state. PMID- 24220915 TI - Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies. AB - BACKGROUND: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. METHODS: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNP). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable adjusted logistic regression models. RESULTS: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk. CONCLUSION: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. IMPACT: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. PMID- 24220918 TI - Differential effects of photoperiod and temperature on hypothalamic monoaminergic activity in the teleost Channa punctatus (Bloch). AB - In Channa punctatus maintained under ambient photothermal conditions (10.5L:13.5D; 13 +/- 2 degrees C) in the postspawning season, hypothalamic dopamine (DA) and norepinephrine (NE) content varied diurnally, but serotonin (5 HT) and monoamine oxidase (MAO) did not. Exposure of the fish to high temperature (25 +/- 2 degrees C), with or without altering the photopheriod, increased the NE and DA content, and NE turnover but decreased DA turnover. Increasing the photoperiod (16L:8D) alone had no significant effect on catecholaminergic (CA) content or activity. When the fish were exposed to long photoperiod, with or without altering the temperature, a day-night variation in 5-HT content and activity was induced in the postspawning season. An increase in temperature alone had no significant effect on 5-HT content or activity. Hypothalamic MAO activity was elevated in fish exposed to high temperature alone, or in combination with long photoperiod, but was not affected significantly by long photoperiod treatment. These results indicate that CA activity is influenced largely by ambient high temperature, whereas serotonergic activity is controlled primarily by photoperiod, with high temperature having an additive effect. MAO activity seems to be influenced by both temperature and photoperiod in this species. PMID- 24220919 TI - The role of glycogen phosphorylase in the regulation of glycogenolysis by insulin and glucagon in isolated eel (Anguilla rostrata) hepatocytes. AB - The effects of porcine, scombroid, and salmon insulins, and bovine and anglerfish glucagons on glycogen depletion and glycogen phosphorylase (GPase) activities were examined in freshly isolated American eel (Anguilla rostrata) hepatocytes. Eel liver GPase in crude homogenates was activated (increase in % GPase a) by phosphorylating conditions and was rapidly inactivated (less than 1 h) when a phosphatase inhibitor (fluoride) was absent. Caffeine inhibits, and AMP activates, the b form of GPase consistent with their effects on rat liver GPase. Both mammalian and fish glucagons increased glucose production in eel hepatocytes, but had more ambiguous effects on glycogen levels and GPase activities. The magnitude of bovine glucagon effects were dependent on the initial glycogen content of the cells; only at glycogen concentrations less than approximately 70 MUmoles.g(-1) did glucagon significantly increase % GPase a. Anglerfish glucagon significantly increased cyclic AMP (cAMP) concentrations by 90% at 10(-7) M, but had no effects at 10(-9) M and 10(-8) M. Scombroid and salmon insulins maintained hepatocyte glycogen concentrations and decreased glucose production, with these effects more pronounced at low (10(-9) to 10(-8) M) rather than high (10(-7) M) hormone concentrations. Porcine and salmon insulins decreased total GPase and % GPase a activities, and salmon insulin decreased CAMP levels, but only at 10(-8) M (by 44%).Glycogen is, therefore, depleted by glucagon and maintained by insulin in freshly isolated American eel hepatocytes, and these changes are accomplished, at least in part, by changes in the activities of GPase. Changes in cAMP do not explain all of the observed hormone effects. PMID- 24220920 TI - Polyunsaturated fatty acid metabolism in cultured fish cells: Incorporation and metabolism of (n-3) and (n-6) series acids by Atlantic salmon (Salmo salar) cells. AB - The incorporation and metabolism of (n-3) and (n-6) polyunsaturated fatty acids (PUFA) supplemented to growing cultures were studied in Atlantic salmon (AS) cells. A fatty acid concentration of 25 MUM considerably altered the fatty acid composition of AS cells without increasing the neutral lipid content of the cells or inducing the production of cytoplasmic lipid droplets. Whereas Delta6 and Delta5 desaturase activities were significantly expressed in AS cells, Delta4 desaturase activity was very low. Both the Delta6 desaturase activity and the Delta5 desaturase activity showed some preference for (n-3) PUFA. PMID- 24220921 TI - Circulatory and ionoregulatory effects of atrial natriuretic peptide on rainbow trout (Salmo gairdneri Richardson) fed normal or high levels of dietary salt. AB - Rainbow trout fed a normal salt diet (1.3% NaCl) or a high salt diet (12% NaCl for at least 6 months) were chronically cannulated in the dorsal aorta and received 10 MUg kg(-1) ANP (1-28 human, UBC-Bioproducts) infused over a 10 min period. This had an insignificant influence on sodium balance, blood electrolytes and branchial sodium fluxes. In fish given a normal diet, the blood pressure and heart rate were uninfluenced by ANP, but pulse pressure was reduced by on average 60% and in some cases was not evident at all. Blood pressure in the fish fed a high salt diet was significantly higher than in the control fish; this together with heart rate and pulse pressure was not affected by ANP administration. PMID- 24220922 TI - Diurnal rhythm of serum steroid hormone levels in the Japanese whiting, Sillago japonica, a daily-spawning teleost. AB - Ovarian developmental stages and serum steroid hormone levels were examined at six different times of day (0100, 0600, 1000, 1300, 1600, 2000 h) in a marine teleost, the Japanese whiting Sillago japonica, which has an asynchronous-type ovary containing oocytes at various stages of development and spawns every day during a period ranging up to three months. The largest oocytes in the ovaries at the active vitellogenic or post-vitellogenic stages were found between 0100 and 1300 h. Oocyte maturation indicated by germinal vesicle breakdown (GVBD) occurred at 1600 h, and ovulated oocytes were observed in the ovaries collected at 2000 h. These processes were accompanied by a significant daily change in serum steroid hormone levels. The serum level of estradiol-17beta showed a peak in fish with mature oocytes sampled at 1600 h. In these fish, the second-largest oocytes in the ovaries were at the initial stage of vigorous vitellogenesis, the secondary yolk stage. Therefore the highest level of serum estradiol-17beta was considered to be due to the second-largest oocytes. Testosterone levels remained low and constant throughout the experimental period. The serum levels of 17alpha,20beta dihydroxy-4-pregnen-3-one (17alpha,20beta-diOHprog) peaked at 1600 h at which time all fish had mature oocytes. These results indicate that the Japanese whiting possesses a diurnal rhythm of oocyte development including vitellogenesis, oocyte maturation and ovulation, and further suggest that daily cycles in oocyte growth and maturation which simultaneously take place in an ovary are regulated by diurnal secretions of estradiol-17beta and the maturation inducing steroid, 17alpha,20beta-diOHprog. PMID- 24220923 TI - Studies on the mode of action of neuropeptide Y (NPY) on maturational gonadotropin (GtH) secretion from perifused rainbow trout pituitary glands. AB - The action of neuropeptide Y (NPY) and gonadotropin releasing hormone (s-GnRH) have been compared on the release of gonadotropin (GtH) by perifused rainbow trout pituitary glands sampled from freshly ovulated female rainbow trout. We have already demonstrated that NPY stimulated the secretion of GtH in vitro.The pituitary responses to s-GnRH and NPY were similar either after repeated 10 min infusions or a one hour prolonged application. In both cases, after the first application, the pituitary did not responded to subsequent secretagogues stimulations, and appeared to be desensitized. The stimulatory action of s-GnRH was partly inhibited (60%) by LH-RH antagonist (DpGlu(1), DPhe(2), DTrp(3-6)) LH RH, which completely inhibited the response to NPY in perifused pituitary glands sampled from freshly ovulated females, but did not modify the response of pituitaries taken from vitellogenic animals in which NPY induced a transient inhibition of the GtH secretion. These results may indicate that the mode of action of NPY would differ between vitellogenic and matured animals. NPY also stimulated the GtH secretion from perifused pituitary dispersed cells prepared from pituitaries taken from freshly ovulated rainbow trout, indicating that NPY may act directly on the pituitary gonadotropic cells to stimulate GtH secretion. PMID- 24220924 TI - Isolation of peroxisomal enoyl-CoA hydratase in rainbow trout and immunochemical identification with the bifunctional enzyme. AB - Peroxisomes are the sites for beta-oxidation of long-chain fatty acids. The peroxisomal bifunctional enzyme (PBE) enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase catalyzes the second and third reactions of the beta-oxidation system. Originally termed PPA-80 for peroxisome-proliferation associated 80,000 MW polypeptide, PBE levels are monitored to measure peroxisome proliferation in rodents and other species. The quantity of a 79,000 MW polypeptide in the light mitochondrial fraction of the liver, as analyzed by SDS-PAGE, increases when rainbow trout are exposed to peroxisome proliferating agents. This correlates with increases in acyl-CoA oxidase activity and peroxisome volume density. In the present study, peroxisomal enoyl-CoA hydratase was purified from trout liver and analyzed by immunoblotting with anti-PBE. A positive reaction with the 79,000 MW polypeptide band was observed providing strong evidence that this is the bifunctional enzyme. PMID- 24220925 TI - A refined parameterization of the analytical Cd-Zn-Te bond-order potential. AB - This paper reports an updated parameterization for a CdTe bond order potential. The original potential is a rigorously parameterized analytical bond order potential for ternary the Cd-Zn-Te systems. This potential effectively captures property trends of multiple Cd, Zn, Te, CdZn, CdTe, ZnTe, and Cd(1-x)Zn(x)Te phases including clusters, lattices, defects, and surfaces. It also enables crystalline growth simulations of stoichiometric compounds/alloys from non stoichiometric vapors. However, the potential over predicts the zinc-blende CdTe lattice constant compared to experimental data. Here, we report a refined analytical Cd-Zn-Te bond order potential parameterization that predicts a better CdTe lattice constant. Characteristics of the second potential are given based on comparisons with both literature potentials and the quantum mechanical calculations. PMID- 24220927 TI - Modifications of the transition flow reactor theory for the more accurate measurement of nitric acid and nitrate and ammonium ions. AB - Sixty five samples were taken with a Transition Flow Reactor (TFR) for the measurement of nitric acid (HNO3) and nitrate particulates (NO 3 (-) ), in a central Athens street having a heavy traffic density, between February 1989 and February 1990. It was established that the TFR theory overestimated HNO3 and underestimated NO 3 (-) . This is caused by the retention of a fraction of the NO2 and a fraction of the HNO2 as NO 2 (-) on the sampler's nylon linear. NO 2 ( ) is in turn oxidized to NO 3 (-) and this is determined as HNO3. Two modifications of the TFR theory are proposed for a better estimation of the HNO3 and NO 3 (-) . With the first modification HNO3 is estimated as being equal to the smaller of two values: HNO3 TFR and the value calculated if it is considered that 91% of HNO3 is retained by the nylon filter. The second modification was based on the quantification of the effect of NO2 on the concentrations of HNO3 and NO 3 (-) . This modification is an improvement on the first one and enables the calculation of a lower limit for the concentration of HNO2. Both modifications improve the accuracy of the TFR sampler in measuring HNO3 and NO 3 (-) , without altering it structurally. It was also found that the nylon filter partially retains some NH3, causing a negative error in the measurement of NH 4 (+) with the TFR. The extent of NH3 retention on the nylon filter is proportional to the HNO3 concentration. This error must be taken into account whenever NH 4 (+) is being determined. PMID- 24220926 TI - Evaluation of density functional methods on the geometric and energetic descriptions of species involved in Cu+-promoted catalysis. AB - We have evaluated the performance of 15 density functionals of diverse complexity on the geometry optimization and energetic evaluation of model reaction steps present in the proposed reaction mechanisms of Cu(I)-catalyzed indole synthesis and click chemistry of iodoalkynes and azides. The relative effect of the Cu(+) ligand on the relative strength of Cu(+)-alkyne interactions, and the strong preference for a pi-bonding mode is captured by all functionals. The best energetic correlations with MP2 are obtained with PBE0, M06-L, and PBE1PW91, which also provide good quality geometries. Furthermore, PBE0 and PBE1PW91 afford the best agreement with the high-level CCSD(T) computations of the deprotonation energies of Cu(+)-coordinated eneamines, where MP2 strongly disagrees with CCSD(T) and the examined DFT functionals. PBE0 also emerged as the most suitable functional for the study of the energetics and geometries of Cu(+) hydrides, while at the same time correctly capturing the influence of the Cu(+) ligands on the metal reactivity. PMID- 24220928 TI - The use of X-ray fluorescence to detect lead contamination of carpeted surfaces. AB - The recognition of the hazards to young children of low-level lead intoxication and the widespread distribution of lead in the urban environment have resulted in massive federal, state, and local lead awareness and abatement programs. Two of the most significant exposure routes of lead to young children are the soils and dusts found within the child's home. Most state and federal lead abatement programs deal with lead-based paint contamination but often do not address the issue of soft-surface contamination, such as that of carpets, furniture, and draperies. Carpets can be a reservoir of contaminated soils and dusts; currently, there exists no standard method to test carpeted surfaces for lead contamination.This paper describes a study that uses X-ray fluorescence (XRF) to test carpeted surfaces for lead contamination. XRF technology is the standard technology used in lead-based paint testing and is known to be an accurate technique to test for lead in soils. This study uses a controlled laboratory atmosphere to evaluate this technology; the objectives are to determine: (1) a lower limit of detection for the instrument; and (2) whether soil loading levels can be differentiated by XRF using trace elements also present in the soil. Results indicate that XRF can easily differentiate soil loading levels (g soil/m(2) carpet). The lower limit of detection of soil lead concentration on the carpet is a function of both soil lead concentration and soil loading; therefore, lead loading (mg Pb/m(2)) is a better indicator of detection limit than soil lead concentration. Lead loading detection levels from 108-258 mg Pb/m(2) were obtained, as compared to a level of 10 000 mg/m(2) (1 mg/cm(2)) for lead on painted surfaces as required by theLead-Based Paint Poisoning Prevention Act.XRF technology has the potential to be a fast, inexpensive screening technique for the evaluation of lead contamination on carpeted surfaces. PMID- 24220929 TI - Appraisal of work hazards and safety in the industrial estate of Jeddah. AB - An environmental study for the appraisal of work hazards and safety in Jeddah Industrial Estate (JIE), Saudi Arabia has been conducted. The study is based upon a representative (stratified random) sample of 44 enterprises, including 52 plants and employing 5830 workers.Nearly 2/3 of the workers have heat exposure, orginating from climatic heat and heat dissipated from industrial operations, while exposure to noise is slightly less, and is attributed to noisy operations and machinery and to lack of meticulous maintenance; both exposures are mild in most of the plants and moderate in some. Mild exposures to nonionizing radiations (UV and IR) and to deficient illumination occur in 25% and 19.2% of the plants studied. Respiratory exposure to chemical agents (organic and inorganic dusts, metal fumes, gases and vapours - including asphyxiants, irritants, liver and nervous system offenders and acid and alkali mists) occurs in 75% of the plants, particularly in the medium-size enterprises plants; however, is mainly mild with a few moderate and severe exposures. Skin absorption contributes to absorption of chemical agents in 29% of the plants, and direct skin contact to chemicals (particularly to lubricating oils) occurs in 81% of the plants.Meanwhile, only eight plants, out of the 32 plants where controls for physical hazards are required (51.2%), apply engineering controls, and even in a few of these plants the efficiency of the control measures has been rated 'bad'. A few of them provide personal protective equipment, and even no maintenance to this equipment is provided.The level of safety is better in the large plants than in the small and medium-size plants; the safety score is the best in the recently established plants, while is the worst in the plastic industry, which is relatively old. The appraisal of fire protection is better than that of the safety, due to efficient supervision of the General Directorate of Civil Defense (GDCD). However, most of the safety problems are managerial and are preventable.First aid is present in all enterprises, as required by the Saudi Labor Laws; however, an in-plant medical service is present in 75% of the large enterprises, in 31.6% of the medium-size and in only 17.6% of the small enterprises. Also, satisfactory medical, accidents and absenteeism records exist in only 15.9% of the enterprises; safety supervision exists in 27.3, and safety education exists in 91% of them, while no environmental monitoring is carried out in any enterprise. Sanitation facilities exist in satisfactory numbers in most of the enterprises; however, their maintenance is poor in most of them, due to lack of hygienic supervision. All enterprises dispose of their liquid wastes into the JIE sewerage system without any treatment, while the solid wastes are collected by the city authorities in 56.8% of them; both wastes are anticipated to cause environmental pollution problems. PMID- 24220930 TI - A bench-scale rock-plant filter investigation. AB - Three bench-scale rock filters containing 0.6 m of gravel were used in this investigation. Two of the filters were planted withSagittaria Iancifolia andScirpus validus, while the third filter was an unvegetated control filter. The wastewater directed through these systems was a synthetic mixture containing nutrient broth as the carbon source. An 80-day experiment was run on the filters using eight combinations of two flow rates and four influent biochemical oxygen demand (BOD5) concentrations, each combination remaining constant for ten days. These combinations resulted in BOD5 surface loadings from 4.63-30.96 g/day/m(2). From other studies of batch and continuous flow rock-plant filter systems, the first-order BOD5 reaction rate constant was found to decrease exponentially with detention time. In this study, however, little correlation was found between BOD5 loading rate and removal percentages, which averaged 69%, 57%, and 47% for theScirpus, Sagittaria, and control systems, respectively. This is probably due to the relatively small change in detention times studied and the short time period of each loading rate. Oxidation/reduction potential (ORP) and dissolved oxygen (DO) measurements within these systems indicated that no free oxygen was available at any depth. Total Kjeldahl nitrogen (TKN) removal was higher in the plant systems relative to the control, with theScirpus system achieving a higher overall removal than theSagittaria system. PMID- 24220931 TI - A study on cadmium phytoremediation potential of water lettuce, Pistia stratiotes L. AB - Aquatic macrophytes have tremendous potential for remediation of the heavy metal cadmium. The objective of this study was to investigate Cd phytoremediation ability of water lettuce, Pistia stratiotes L. The study was conducted with 5, 10, 15 and 20 mg L(-1) CdCl2 in hydroponic system for 21 days and the Cd concentrations in the root and shoot tissues were estimated by atomic absorption spectroscopy. The values obtained were used to evaluate the bioconcentration factor (BCF), translocation factor (TF) and translocation efficiency of this plant. The plant showed high Cd tolerance of up to 20 mg L(-1) but there was a general trend of decline in the root and shoot biomass. The maximum BCF values for root and shoot tissues were 2,294 and 870 respectively, obtained for 5 mg L( 1) Cd, which indicated that the plant was a Cd hyperaccumulator. The TF maxima was found to be 0.6 and as much as 60 % root to shoot translocation efficiency was observed for 15 mg L(-1) Cd which points towards the suitability of water lettuce for removing Cd from surface waters. PMID- 24220932 TI - Antitumor effects of recombinant antivascular protein ABRaA-VEGF121 combined with IL-12 gene therapy. AB - Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the tumor. Anticancer therapeutic strategy bringing together antiangiogenic and immunostimulating agents has emerged as a promising approach. We here investigated whether therapy directed against preexisting vessels, combined with an immunomodulatory factor would be equally effective in arresting tumor growth. To this goal, we investigated the effectiveness of ABRaA-vascular endothelial growth factor isoform 121 (VEGF121), an antivascular drug constructed by us. It is a fusion protein composed of VEGF121, and abrin A chain (translation-inhibiting toxin). We used it in combination with interleukin (IL-12) gene therapy and tried to inhibit B16-F10 melanoma tumor growth. ABRaA-VEGF121 is a chimeric recombinant protein capable of destroying tumor vasculature and triggering necrosis in the vicinity of damaged vessels. IL-12 cytokine, in turn, activates both specific and non specific immune responses. Our results demonstrate that combination of ABRaA VEGF121 antivascular agent with immunostimulatory cytokine IL-12 indeed inhibits tumor growth more effectively than either agent alone, leading to complete cure of ca. 20 % mice. Post-therapeutic analysis of tumors excised from mice treated with combination therapy showed decreased numbers of blood microvessels in the tumor microenvironment, lowered numbers of regulatory T lymphocytes, as well as showed higher levels of CD4(+) and CD8(+) as compared to control mice. It seems that bringing together antivascular strategy and the action of immunostimulating agents indeed inhibits growth of tumors. PMID- 24220933 TI - Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. AB - INTRODUCTION: Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during chemotherapy. MATERIALS AND METHODS: TUBB3 expression was investigated by immunohistochemistry performed on diagnostic biopsies and on available subsequent resection specimens in 65 NSCLC patients stage T1-3N0-2 who received neoadjuvant carboplatin and paclitaxel (NAC-group). Another group of 53 NSCLC patients stage T1-4N0-1 was treated with surgery alone without preceding chemotherapy (OP-group). Paired repeated samples were compared in order to evaluate for changes in TUBB3 expression. RESULTS: No statistically significant change in TUBB3 expression was observed between initial diagnostic biopsies and subsequent surgical resections of primary tumors in either the OP-group (p = 0.124) or the NAC-group (p = 0.414). When dichotomized into high and low TUBB3 expression, discordance between diagnostic biopsies and resection specimens of the primary tumors occurred in 22 % and 40 % in the OP group and NAC-group, respectively (p = 0.169). Significantly more patients having low TUBB3 expression experienced down-staging during neoadjuvant chemotherapy compared to patients having high TUBB3 expression (p = 0.022). CONCLUSION: A high degree of discordance of TUBB3 expression between paired repeated tumor samples was observed, which likely reflects intratumoral heterogeneity. This emphasizes a need for optimal tumor tissue samples in order to stratify patients based on TUBB3 expression. No significant changes in TUBB3 expression after neoadjuvant carboplatin and paclitaxel chemotherapy occurred, suggesting no need for rebiopsy in case second-line chemotherapy with microtubule interfering cytotoxic treatments is necessary. PMID- 24220934 TI - Assessing physico-chemical compatibility of concomitantly diluted antiemetics including palonosetron-HCl and fosaprepitant dimeglumine. PMID- 24220935 TI - Circulating proteins as potential biomarkers of sunitinib and interferon-alpha efficacy in treatment-naive patients with metastatic renal cell carcinoma. AB - PURPOSE: We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-alpha), first-line in metastatic renal cell carcinoma (mRCC), by analyzing plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGF receptor-3 (sVEGFR-3) and interleukin (IL) 8. METHODS: Seven hundred and fifty mRCC patients were randomized to oral sunitinib 50 mg/day in repeated cycles of a 4-week on/2-week off schedule or IFN alpha 9 million units subcutaneously thrice weekly. Plasma samples collected from a subset of 63 patients on days 1 and 28 of cycles 1-4 and at end of treatment were analyzed by ELISA. RESULTS: Baseline characteristics of biomarker-evaluated patients in sunitinib (N = 33) and IFN-alpha (N = 30) arms were comparable to their respective intent-to-treat populations. By univariate Cox regression analysis, low baseline soluble protein levels were associated with lower risk of progression/death (all P < 0.05): in both treatment arms, baseline VEGF-A and IL 8 were associated with overall survival (OS) and baseline VEGF-C with progression free survival (PFS); in the sunitinib arm, baseline VEGF-A was associated with PFS and baseline sVEGFR-3 with PFS and OS; in the IFN-alpha arm, baseline IL-8 was associated with PFS. In multivariate analysis, baseline sVEGFR-3 and IL-8 remained independent predictors of OS in the sunitinib arm, while no independent predictors of outcome remained in the IFN-alpha arm. Pharmacodynamic changes were not associated with PFS or OS for any plasma protein investigated. CONCLUSIONS: Our findings suggest that, in mRCC, baseline VEGF-A and IL-8 may have prognostic value, while baseline sVEGFR-3 may predict sunitinib efficacy. PMID- 24220936 TI - Phase I dose-escalation study of oral vinflunine in combination with erlotinib in pre-treated and unselected EGFR patients with locally advanced or metastatic non small-cell lung cancer. AB - BACKGROUND: Erlotinib, the epidermal growth factor receptor tyrosine kinase inhibitor, and the intra-venous vinflunine vinca alkaloid microtubule inhibitor have been shown to be effective in the setting of non-small-cell lung cancer (NSCLC) palliative patients with acceptable toxicities. This phase I study was conducted to determine the maximal tolerated dose (MTD) and the safety of an all oral combination. A potential pharmacokinetic drug-drug interaction was also investigated. PATIENTS AND METHODS: Patients with unresectable stage IIIB or stage IV NSCLC who failed one or two previous chemotherapy regimens were treated with flat doses of oral vinflunine from day 1 to day 5 and from day 8 to day 12 every 3 weeks and erlotinib daily on a continuous basis. The dose levels of vinflunine/erlotinib were 95/100, 115/100, 115/150 and 135/100 mg. RESULTS: Thirty patients were enroled. The recommended dose was 115/150 mg and the MTD 135/100 mg. Dose-limiting toxicities included grade 3 febrile neutropenia (1 patient) and related death (1 patient). Non-haematologic grade 3/4 toxicities included fatigue, condition aggravated, hypokalaemia, tumour pain, acneiform dermatitis, diarrhoea, hyperbilirubinaemia and pulmonary haemorrhage, in one patient each. Of 25 patients evaluable for tumour response, 2 patients had partial response and 20 patients had stable disease. CONCLUSION: The recommended doses for oral vinflunine and erlotinib combination were, respectively, 115 mg/day from day 1 to day 5 and from day 8 to day 12 every 3 weeks and 150 mg/day. There was no mutual impact on pharmacokinetics. The combination was safe but evaluation in phase II is needed to further refine the activity and toxicity that can be expected with prolonged administration of this dose schedule. PMID- 24220937 TI - Changes of cytokines in patients with liver cirrhosis and advanced hepatocellular carcinoma treated by sorafenib. AB - PURPOSE: Recently, the oral multikinase inhibitor sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). Tumor necrosis factor (TNF) induces apoptosis of tumor cells by binding to TNF-related apoptosis-inducing ligand, while binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes also causes apoptosis. The aim of this study was to retrospectively evaluate changes of cytokines in patients with liver cirrhosis (LC) and aHCC receiving sorafenib therapy. METHODS: Fifty-seven adult Japanese LC patients received sorafenib for aHCC (200-800 mg/day for 4 weeks) between 2009 and 2012 at our hospital. Blood samples were collected in the early morning before and after treatment, and the serum levels of soluble TNF-alpha (sTNF alpha), soluble TNF receptor (sTNF-R), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. RESULTS: Ten patients were treated with sorafenib at 200 mg/day (200 mg group), 37 patients were given 400 mg/day (400 mg group), and 10 patients received 800 mg/day (800 mg group). The serum level of sTNF-alpha was significantly increased after treatment compared with before treatment in the 400 and 800 mg groups. The serum level of sTNF-R also showed a significant increase after treatment in the 400 mg group, although there was no significant difference of sTNF-R between before and after treatment in the 200 and 800 mg groups. sFas showed a significant decrease after treatment compared with before treatment in the 400 and 800 mg groups, although the serum level of sFas L never exceeded 0.15 ng/ml. CONCLUSIONS: These findings suggest that treatment with sorafenib at doses >=400 mg/day might promote TNF-related or Fas-related apoptosis by increasing the circulating level of TNF-alpha or decreasing that of sFas. PMID- 24220938 TI - Convergence of the endocytic and lysosomal pathways in soybean protoplasts. AB - Ultrastructural analysis of endocytosis of cationized ferritin (CF) has been combined with ultrastructural localization of acid phosphatases (AcPase) in soybean (Glycine max (L.) Merr.) protoplasts. While CF is an electron-dense marker of organelles of the endocytic pathway, ultrastructural histochemistry of AcPase identifies the organelles involved in the synthesis, transport, and storage of lytic-compartment enzymes, i.e. the lysosomal pathway. Acid phosphatases have been localized using both lead- and cerium-precipitation techniques. Protoplasts have been exposed to CF for 5 min, 30 min, or 3 h and processed for AcPase localization. At 5 min, smooth vesicles contain both CF and AcPase. By 30 min, Golgi cisternae and multivesicular bodies contain both labels. By 3 h, vacuoles become labelled with both CF and AcPase. The large central vacuoles contain intraluminal membranes which are associated with both AcPase and CF. These observations extend the analogy between plant vacuoles and animal lysosomes and demonstrate the points at which the endocytic pathway of plants converges with the lysosomal pathway. PMID- 24220939 TI - Regulation of electron transport in maize mesophyll chloroplasts: The relationship between chlorophyll a fluorescence quenching and O2 evolution. AB - The relationship between the redox state of the primary electron acceptor of photosystem II (QA) and the rate of O2 evolution in isolated mesophyll chloroplasts from Zea mays L. is examined using pulse-modulated chlorophyll a fluorescence techniques. A linear relationship between photochemical quenching of chlorophyll fluorescence (qQ) and the rate of O2 evolution is evident under most conditions with either glycerate 3-phosphate or oxaloacetate as substrates. There appears to be no effect of the transthylakoid pH gradient on the rate of electron transfer from photosystem II into QA in these chloroplasts. However, the proportion of electron transport occurring through cyclic-pseudocyclic pathways relative to the non-cyclic pathway appears to be regulated by metabolic demand for ATP. The majority of non-photochemical quenching in these chloroplasts at moderate irradiances appeared to be "energy"-dependent quenching. PMID- 24220940 TI - The cell wall of Chlamydomonas reinhardtii gametes: Composition, structure and autolysin-mediated shedding and dissolution. AB - The cell walls of Chlamydomonas gametes are multilayered structures supported on frameworks of polypeptides extending from the plasma membrane. The wall polypeptide catalogue reported by Monk et al. (1983, Planta 158, 517-533) and extended by U.W. Goodenough et al. (1986, J. Cell Biol. 103, 405-417) was re evaluated by comparative analysis of mechanically isolated cell walls purified from several strains. The extracellular locus of wall polypeptides was verified by in vivo iodogen-catalysed iodination and by autolysin-mediated elimination of the bulk of these polypeptides from the cell surface. Three (w15, w16, w17) and possibly four (w14) polypeptides were located to the most exterior aspect of the wall because of their susceptibility to Enzymobeadcatalysed iodination and their retention by a cell-wall-less mutant. The composition of shed walls stabilised with ethylenediaminetetraacetic acid during natural mating and kinetic analysis of the dissolution of walls purified from a bald-2 mutant demonstrated the rapid and specific destruction of polypeptide w3. Differential solubilisation of wall polypeptides occurred after loss of w3. Wall dissolution, characterised by the generation of fishbone structures from the W2 layer, gave as many as four additional polypeptides. Charged detergents and sodium perchlorate extracted a comparable range of polypeptides at room temperature from mechanically isolated walls, i.e. components of the W4-W6 layers, hot sodium dodecyl sulphate solubilised framework polypeptides, while reducing agent was required to solubilise the W2 layer. A model of wall structure is presented. PMID- 24220941 TI - The use of a chloride-sensitive fluorescent probe to measure chloride transport in isolated tonoplast vesicles. AB - A fluorescence method for the direct measurement of Cl(-) transport in isolated tonoplast vesicles is described. This technique utilises the Cl(-)-sensitive fluorescent compound, 6-methoxy-1-(3-sulfonatopropyl)quinolinium (SPQ). This is a water-soluble compound with excitation and emission wavelengths of 350 and 440 nm, respectively. Its fluorescence is quenched by Cl(-), Br(-), I(-), SCN(-), NO 2 (-) and tetraphenylborate but not by NO 3 (-) , SO 4 (2-) , iminodiacetate or malate. These effects are independent of pH. This compound was loaded into tonoplast vesicles from red beet (Beta vulgaris L.) storage roots or from barley (Hordeum vulgare L.) roots by incubation at 37 degrees C and the external probe was then removed by repeated centrifugation of the vesicles in SPQ-free medium. In this way a large proportion of the observed fluorescence signal was from the interior of the vesicles, and its quenching could be used to monitor, quantitatively, and in real time, the intravesicular Cl(-) concentration. In this paper we describe some of the problems encountered in using this probe to measure Cl(-) transport in tonoplast vesicles, how these were overcome and some characteristics of Cl(-) transport at the tonoplast as measured by the probe. PMID- 24220942 TI - Pathways of assimilation and transfer of fixed nitrogen in coralloid roots of cycad-Nostoc symbioses. AB - Freshly detached coralloid roots of several cycad species were found to bleed spontaneously from xylem, permitting identification of products of nitrogen transfer from symbiotic organ to host. Structural features relevant to the export of fixed N were described for Macrozamia riedlei (Fisch. ex Gaud.) Gardn. the principal species studied. Citrulline (Cit), glutamine (Gln) and glutamic acid (Glu), the latter usually in a lesser amount, were the principal translocated solutes in Macrozamia (5 spp.), Encephalartos (4 spp.) and Lepidozamia (1 sp.), while Gln and a smaller amount of Glu, but no Cit were present in xylem sap of Bowenia (1 sp.),and Cycas (2 spp.). Time-course studies of (15)N enrichment of the different tissue zones and the xylem sap of (15)N2-pulse-fed coralloid roots of M. riedlei showed earlier (15)N incorporation into Gln than into Cit, and a subsequent net decline in the (15)N of Gln of the coralloid-root tissues, whereas Cit labeling continued to increase in inner cortex and stele and in the xylem sap. Hydrolysis of the (15)N-labeled Cit and Gln consistently demonstrated much more intense labeling of the respective carbamyl and amide groups than of the other N-atoms. Coralloid roots of M. riedlei pulse-fed (14)CO2 in darkness showed (14)C labeling of aspartic acid (Asp) and Cit in all tissue zones and of Cit of xylem bleeding sap. Lateral roots and uninfected apogeotropic roots of M. riedlei and M. moorei also incorporated (14)CO2 into Cit. The (14)C of Cit was restricted to the carbamyl-C. Comparable (15)N2 and CO2-feeding studies on corallid roots of Cycas revoluta showed Gln to be the dominant product of N2 fixation, with Asp and alanine as other major (14)C-labeled amino compounds, but a total absence of Cit in labeled or unlabeled form. PMID- 24220943 TI - Monoclonal antibodies identify common and differentiation-specific antigens on the plasma membrane of guard cells of Vicia faba L. AB - Monoclonal antibodies were raised against the plasma membrane of Vicia faba L. guard cells by immunizing either with total membranes from purified guard-cell protoplasts or with sealed, predominantly right-side-out plasma-membrane vesicles prepared from abaxial epidermes of V. faba by aqueous two-phase partitioning. Hybridoma screening was performed by enzyme-linked immunosorbent assay using polystyrene-adsorbed plasma-membrane vesicles as solid phase and by indirect immunofluorescence analysis using unfixed, immobilized protoplasts in a microvolume Terasaki assay. A range of monoclonal antibodies was characterized and is reported here. One monoclonal antibody, G26-6-B2, is guard-cell-specific and does not react with mesophyll-cell protoplasts of the same species. It binds to a periodate-resistant but trypsin-labile epitope, probably a differentiation specific plasma-membrane protein. PMID- 24220944 TI - Antibodies to pollen exines. AB - A polyclonal antiserum and monoclonal antibodies have been prepared to purified pollen exines of Calocedrus decurrens Florin. The location of the antigen is in the exine, as shown by light-and electron-microscopic immunocytochemistry. The greatest reduction in antibody binding follows treatment of the exine with chemicals known to alter sporopollenin. These results provide evidence that sporopollenin is antigenic. Exines of ten species of gymnosperms and angiosperms also bound the polyclonal antiserum, indicating similarity of sporopollenin structure. PMID- 24220945 TI - A guanosine 5'-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts. AB - A guanosine 5'-triphosphate (GTP)-dependent protein kinase was detected in preparations of outer chloroplast envelope membranes of pea (Pisum sativum L.) chloroplasts. The protein-kinase activity was capable of phosphorylating several envelope-membrane proteins. The major phosphorylated products were 23- and 32.5 kilo-dalton proteins of the outer envelope membrane. Several other envelope proteins were labeled to a lesser extent. Following acid hydrolysis of the labeled proteins, most of the label was detected as phosphoserine with only minor amounts detected as phosphothreonine. Several criteria were used to distinguish the GTP-dependent protein kinase from an ATP-dependent kinase also present in the outer envelope membrane. The ATP-dependent kinase phosphorylated a very different set of envelope-membrane proteins. Heparin inhibited the GTP-dependent kinase but had little effect upon the ATP-dependent enzyme. The GTP-dependent enzyme accepted phosvitin as an external protein substrate whereas the ATP-dependent enzyme did not. The outer membrane of the chloroplast envelope also contained a phosphotransferase capable of transferring labeled phosphate from [gamma (32)P]GTP to ADP to yield (gamma-(32)P]ATP. Consequently, addition of ADP to a GTP-dependent protein-kinase assay resulted in a switch in the pattern of labeled products from that seen with GTP to that typically seen with ATP. PMID- 24220946 TI - Patterns of protein synthesis in dormant and growing vegetative buds of pea. AB - Lateral buds on intact pea plants (Pisum sativum L. cv. Alaska) remain dormant until they are stimulated to develop by decapitating the terminal bud. Using two dimensional gel electrophoresis, we have examined the protein content of terminal and lateral buds from intact plants and from plants at various times after decapitation. Silver-staining and in-vivo-labeling demonstrated very different sets of proteins. The level of expression of 18 stained and 25 labeled proteins was altered when growth was stimulated; this represents 3.4% and 9.1% of the total proteins detected by each method, respectively. Within 24 h of being stimulated, lateral buds doubled in length and their protein content was qualitatively nearly the same as that of terminal buds. Six hours after decapitation, before the onset of detectable growth, the overall pattern of protein synthesis in lateral buds was more like that of growing lateral buds or of terminal buds than that of dormant lateral buds. Direct application of N(6) furfurylaminopurine (kinetin) to buds on intact plants stimulated their growth and resulted in the same pattern of protein synthesis as did decapitation. Inhibition of bud growth by addition of indole-3-acetic acid to the stumps of decapitated plants resulted in the synthesis of dormancy-related proteins. Lateral buds at all stages of development incorporated labeled amino acids at similar rates, indicating that metabolic activity is not a component of dormancy in these buds. PMID- 24220947 TI - Role of plastidial acyl-acyl carrier protein: Glycerol 3-phosphate acyltransferase and acyl-acyl carrier protein hydrolase in channelling the acyl flux through the prokaryotic and eukaryotic pathway. AB - In order to investigate whether the relative activities of the plastidial acyl acyl carrier protein (ACP):glycerol 3-phosphate acyltransferase (EC 2.3.1.15) and acyl-ACP hydrolase play a role in controlling the acyl flux through the prokaryotic and eukaryotic pathway, we determined these enzymic activities in stroma fractions from 16:3- and 18:3-plants using glycerol 3-phosphate and labelled acyl-ACP as substrates. Several factors were examined which might influence the activities within plastids, such as leaf development, salts at physiological concentrations, stroma pH and substrates available to the enzymes. An appreciable alteration of the two enzymic activities was only observed with changes in the pH and substrate concentration, especially the concentration of glycerol 3-phosphate. An increase in pH from 7 to 8 resulted in a decreased ratio of acyltransferase versus hydrolase activity in stroma fractions from both pea (Pisum sativum L.) and spinach (Spinacia oleracea L.), whereas exogenously added glycerol 3-phosphate, which only influenced the acyltransferase, raised this ratio. On the other hand, the relative activities of the two enzymes stayed rather constant at oleoyl-ACP concentrations between 1 and 2 MUM not only when it was offered alone but also in a mixture with palmitoyl-ACP. At pH 8, the stroma pH of illuminated chloroplasts, and at physiologically relevant substrate concentrations we observed clear differences between the 16:3-plants spinach and mustard (Sinapis alba ssp. alba L.) and the 18:3-plants pea and maize (Zea mays L.). In accordance with the different proportions of prokaryotic glycerolipids in the two groups of plants, pea and maize showed distinctly lower ratios of acyltransferase versus hydrolase activity than spinach and mustard. Consequently the relative activities of the plastidial glycerol 3-phosphate acyltransferase and acyl-ACP hydrolase can play a decisive role in controlling the acyl flux through the different pathways at least in these plants. PMID- 24220948 TI - Preparation and characterisation of monoclonal and polyclonal antibodies to maize membrane auxin-binding protein. AB - Binding proteins, thought to be auxin receptors, can be solubilised from maize (Zea mays L.) membranes after acetone treatment. From these crude extracts, receptor preparations of over 50% purity can be obtained by a reliable, straight forward procedure involving three chromatographic steps - anion exchange, gel filtration and high-resolution anion exchange. Such preparations have been used to immunise rats for subsequent production of monoclonal antibodies. By the further step of native polyacrylamide gel electrophoresis the semi-purified preparations yield homogeneous, dimeric (22-kilodalton, kDa) auxin-binding protein, which has been used to produce a polyclonal rabbit antiserum. The preliminary characterisation of this antiserum and of the five monoclonal antibodies is presented. Two of the monoclonal antibodies specifically recognise the major 22-kDa-binding protein polypeptide whilst the other three recognise, in addition, a minor 21-kDa species. All the monoclonal antibodies recognise the polypeptide rather than the glycan side chain and the polyclonal antiserum also recognises deglycosylated binding protein. The antibodies have been used to quantify the abundance of auxinbinding protein in a number of tissues of etiolated maize seedlings. Root membranes contain 20-fold less binding protein than coleoptile membranes. PMID- 24220949 TI - Distribution of photorespiratory enzymes between bundle-sheath and mesophyll cells in leaves of the C3-C 4 intermediate species Moricandia arvensis (L.) DC. AB - In order to study the location of enzymes of photorespiration in leaves of the C3 C4 intermediate species Moricandia arvensis (L.). DC, protoplast fractions enriched in mesophyll or bundlesheath cells have been prepared by a combination of mechanical and enzymic techniques. The activities of the mitochondrial enzymes fumarase (EC 4.2.1.2) and glycine decarboxylase (EC 2.1.2.10) were enriched by 3.0- and 7.5-fold, respectively, in the bundle-sheath relative to the mesophyll fraction. Enrichment of fumarase is consistent with the larger number of mitochondria in bundle-sheath cells relative to mesophyll cells. The greater enrichment of glycine decarboxylase indicates that the activity is considerably higher on a mitochondrial basis in bundle-sheath than in mesophyll cells. Serine hydroxymethyltransferase (EC 2.1.2.1) activity was enriched by 5.3-fold and glutamate-dependent glyoxylate-aminotransferase (EC 2.6.1.4) activity by 2.6-fold in the bundle-sheath relative to the mesophyll fraction. Activities of serine- and alanine-dependent glyoxylate aminotransferase (EC 2.6.1.45 and EC 2.6.1.4), glycollate oxidase (EC 1.1.3.1), hydroxypyruvate reductase (EC 1.1.1.81), glutamine synthetase (EC 6.3.1.2) and phosphoribulokinase (EC 2.7.1.19) were not significantly different in the two fractions. These data provide further independent evidence to complement earlier immunocytochemical studies of the distribution of photorespiratory enzymes in the leaves of this species, and indicate that while mesophyll cells of M. arvensis have the capacity to synthesize glycine during photorespiration, they have only a low capacity to metabolize it. We suggest that glycine produced by photorespiratory metabolism in the mesophyll is decarboxylated predominantly by the mitochondria in the bundle sheath. PMID- 24220950 TI - Movement of Lucifer Yellow CH in potato tuber storage tissues: A comparison of symplastic and apoplastic transport. AB - The fluorescent dye Lucifer Yellow CH (LYCH) was introduced directly into the symplast of potato (Solanum tuberosum L.) tuber storage parenchyma by microinjection and also into the apoplast through cuts made in the stolon cortex. Microinjected LYCH moved away rapidly from a single storage cell and spread radially via the symplast. When the microinjected tissue was subsequently fixed in glutaraldehyde and sectioned the dye was seen clearly to be localised in the cytoplasm but not in the vacuole. In comparison, when LYCH was introduced into cuts made in the stolon cortex the dye entered the tuber by the xylem and subsequently spread apoplastically. No movement of dye was observed in the phloem. In glutaraldehyde-fixed tissues, in which LYCH was introduced to the apoplast, the dye was found within xylem vessels, in the cell walls and in intercellular spaces. Wall regions, possibly associated with plasmodesmata, became stained by the dye as it moved through the apoplast. Three hours after introduction of the dye to the stolon, intense deposits of LYCH were found in the vacuoles of all cells in the tuber, many aligned along the tonoplast. Differentiating vascular parenchyma elements contained large amounts of dye within enlarging vacuoles. However, with the exception of plasmolysed and-or damaged cells, LYCH was absent from the cytoplasm following its introduction to the plasmalemma it is suggested that the most likely pathway from the cell wall to the vacuole was by endocytosis, the dye being transported across the cytoplasm in membrane-bound vesicles. Clathrin-coated vesicles were abundant in the storage cells, providing a possible endocytotic pathway for dye movement. The significance of these observations is discussed in relation to the movement of LYCH in plant tissues and to the movement of solutes within and between storage cells of the tuber. PMID- 24220951 TI - Uptake of Lucifer Yellow CH into intact barley roots: Evidence for fluid-phase endocytosis. AB - Intact barley (Hordeum vulgare L.) roots have been shown to take up the highly fluorescent dye Lucifer Yellow CH (LYCH) into their cell vacuoles. In the apical 1 cm of root tip, differentiating and dividing cells showed a prolific uptake of LYCH into their provacuoles. The LYCH was retained during fixation, apparently becoming bound to electron-dense material in the vacuoles. The dye freely entered the apoplast of roots in which the Casparian band was not developed, being taken up into the vacuoles of cells in both the cortex and stele. However, when LYCH was applied to a 1-cm zone approx. 6 cm behind the root tip the Casparian band on the radial walls of the endodermis completely prevented the dye from entering the cells of the stele, only the cell walls and vacuoles of the cortical cells taking up the dye. The inability of LYCH to cross the plasmalemma of the endodermal cells and enter the stele via the symplast substantiates previous claims that the dye is unable to cross the plasmalemma of plant cells. The results are discussed in the light of recent demonstrations that LYCH is a particularly effective marker for fluid-phase endocytosis in animal and yeast cells. A calculation of the energetic requirements for LYCH uptake into barley roots supports the contention that LYCH is taken up into the vacuoles of plant cells by fluid-phase endocytosis. PMID- 24220952 TI - Apparent induction of key enzymes of the glyoxylic acid cycle in senescent barley leaves. AB - The activities of two key enzymes of the glyoxylic-acid cycle, isocitrate lyase and malate synthase, can barely be detected in mature, presenescent primary leaves of barley (Hordeum vulgare L.) but are apparently induced in senescent leaf tissue. Upon incubation of leaf segments in permanent darkness, the activities appear and increase dramatically up to the sixth day and thereafter decline. The glyoxylic-acid cycle may thus be functional during foliar senescence. The main period of galactolipid loss is characterized by RQ values as low as 0.63, indicating that long-chain fatty acids produced from thylakoidal acyl-lipids may be utilized for gluconeogenesis involving corresponding glyoxisomal metabolic pathways. Foliar senescence may be characterized by a peroxisomeglyoxysome transition analogous to the glyoxisome-peroxisome transition in greening cotyledons of fat-storing seeds. PMID- 24220953 TI - [Hybrid operation theatre]. PMID- 24220955 TI - [Laparoscopic versus open total mesorectal excision for rectal cancer. Results from the actual medical care situation]. PMID- 24220954 TI - [The interdisciplinary hybrid operation theatre. Current experience and future]. AB - Since June 2013 a hybrid operation theatre is used interdisciplinary in the department for surgery of Ulm University. In this operation theatre a floor-based flat panel c-arm, which is mounted on a robotic arm that can be controlled by the surgeon in a sterile environment, is linked to the operating table. Furthermore for the first time it was possible to integrate a navigation system in this setting. The interdisciplinary utilization (trauma, neurosurgery, cardiac and vascular surgery) makes this hybrid operation theatre very time and cost effective. In the orthopedic trauma department this system is mainly used for traumatic and oncologic pelvic and spinal injuries. In these anatomical regions the excellent image quality and large field of view of the robotic flat panel detector based 3D imaging combined with an intraoperative navigation system is a huge advantage. The system can also be used for complex fractures of the extremities. In the future there will be an integration of further imaging modalities and referenced holding devices in this setting. PMID- 24220956 TI - [Surgical management of disappearing colorectal liver metastases]. PMID- 24220957 TI - [Laparoscopic anterior hemi-fundoplication versus Nissen fundoplication. Long term results]. PMID- 24220958 TI - [Antibiotic prophylaxis in thyroid gland surgery]. PMID- 24220959 TI - Comparison of the response to aluminum toxicity in gametophyte and sporophyte of four tomato (Lycopersicon esculentum Mill.) cultivars. AB - We tested pollen from four tomato cultivars differing in sensitivity to aluminum in the sporophyte to determine if Al sensitivity was also expressed in pollen. Pollen sensitivity to Al was measured by the ability to germinate and grow in a control solution after a short period in a high concentration of Al. The response was ranked and compared to the Al sensitivity ranking of the four cultivars based on top growth in Al toxic soil. In addition, seedlings from the most and least sensitive cultivars, based on pollen germination, were compared for Al sensitivity in nutrient solutions. Treatment with Al significantly reduced pollen germination in the two more sensitive cultivars, but not in the two more resistant cultivars. However, the ranking was not the same as that based on the shoot growth of the sporophyte. Root growth as a criterion of sporophytic Al sensitivity produced results similar to pollen germination. The study suggests that although the correspondence is better for some phenotypic responses of the sporophyte than others, Al tolerance appears to be another character expressed in both pollen and sporophyte. PMID- 24220960 TI - Allozyme variation among the spontaneous species of Sorghum section Sorghum (Poaceae). AB - A survey of allozyme variation among the spontaneous taxa of Sorghum section Sorghum was undertaken. Eight plants each of 90 accessions representing the diploid S. bicolor (ssp. arundinaceum and drummondii) and the tetraploids S. almum and S. halepense were analyzed for 17 enzyme systems encoded by 30 loci. Low levels of variation were found within and among accessions, although there was more variation than is typical of inbreeding species. We found an average of 3.2 alleles per locus in ssp. arundinaceum, with a mean expected heterozygosity for the accessions of 0.034 and total panmictic heterozygosity of 0.154. An analysis of the apportionment of genetic variation among accessions of ssp. arundinaceum indicated that 26% of the variation occurs within accessions and 74% among accessions. Cultivated sorghum contains far less allozymic variation than ssp. arundinaceum, its presumed progenitor. This is consistent with the prediction that cultivated sorghum experienced a loss of genetic variation during domestication. For the most part, cultivated sorghum contains a subset of the allozymes found in ssp. arundinaceum. Principal component analysis revealed continuous variation among the accessions and geographic regions, with accessions failing to segregate into discrete clusters. However, accessions of race virgatum of ssp. arundinaceum occupied one end of the continuum and were, in that sense, distinguished from the other accessions. Similarly, most accessions of S. halepense and S. almum occupied the central portion of the continuum. The allozymic data presented here are consistent with the hypothesized origin of S. halepense via autopolyploidy or segmental allopolyploidy. PMID- 24220961 TI - Asymmetric somatic hybrids between Lycopersicon esculentum and irradiated Lycopersicon peruvianum : 1. Cytogenetics and morphology. AB - Asymmetric somatic hybrids of Lycopersicon esculentum and Lycopersicon peruvianum were obtained by fusion of leaf protoplasts from both species after irradiation of protoplasts or leaf tissue of L. peruvianum with 50, 300, or 1,000 Gy of gamma rays. These radiation doses were sufficient to abolish the growth of the L. peruvianum protoplasts. The hybrids were selected for their ability to regenerate plants; this regeneration capacity derived from L. peruvianum. All asymmetric hybrid plants were aneuploid. The ploidy level, the morphology, and the regeneration rate were analyzed in relation to the radiation dose applied to L. peruvianum. After a low dose (50 Gy), most hybrids had near-triploid chromosome numbers, whereas after a high dose (300 or 1,000 Gy), most hybrids had near pentaploid numbers. The morphology of the asymmetric hybrids was intermediate between that of L. esculentum and symmetric somatic hybrids of both species (obtained without irradiation treatment), and approached the morphology of L. esculentum to a greater extent after a high dose of irradiation. The asymmetric hybrids regenerated more slowly than the symmetric hybrids and regeneration proceeded more slowly after a high dose than after a low dose of irradiation. The high-dose hybrids also grew more slowly, flowered less, and set fruits less than the low-dose hybrids. No seeds could be obtained from any asymmetric hybrid. PMID- 24220962 TI - Mixing ability analysis of wheat cultivar mixtures under diseased and nondiseased conditions. AB - Mixing ability analyses, adapted from combining ability analyses used in plant breeding, were performed on yield and stripe rust (Puccinia striiformis) severity data for two-way mixtures among either four or five club wheat (Triticum aesitivum) cultivars grown in five environments. Initially, two statistics were calculated for each trait: general mixing ability (GMA), the average performance of a cultivar over all of the mixtures, and specific mixing ability (SMA), the deviation of a mixture from the estimated performance of the pair based on its average performance in mixtures. General mixing ability was further divided into two components: genotype performing ability (GPA), the innate ability of a cultivar to yield and resist disease in pure stand, and true general mixing ability (TGMA), the average ability of a cultivar to influence yield and disease when mixed with other cultivars. Significant mean squares for genotypes, GMA, SMA, and TGMA were found for all of the traits in most environments. Examination of TGMA and SMA revealed cultivars and cultivar combinations that were statistically better "mixers" than the others. Some of the significant effects were probably due to the use of cultivars that differed in height and stripe rust resistance, but for other combinations there was no apparent explanation for enhanced mixing ability. PMID- 24220963 TI - Prediction of heterosis in crosses between inbred lines of Drosophila melanogaster. AB - The aim of the experiment was to determine if the estimated genetic distance between two populations could be used to predict the amount of heterosis that would occur when they were crossed. Eight lines of known relatedness to each other were produced by eight generations of sib mating and sub-lining. This produced lines that varied in coefficient of coancestry from zero to 0.78. Fourteen reciprocal crosses of these lines were used to measure heterosis for larval viability and adult fecundity. Gene frequencies at six polymorphic enzyme loci were used to estimate the genetic distances between lines, which were then compared with the known degrees of coancestry. The estimated genetic differences were poorly correlated with the known coancestry coefficients (r=0.4), possibly due to the small number of loci typed. Also genetic distances were only about 1/3 of what was expected. Selection acting on blocks of genes linked to the enzyme loci probably prevented the expected increase in homozygosity. Coancestry coefficient was correlated with heterosis (r=0.44-0.71). This level of correlation implied differences in heterosis among parent lines with the same level of coancestry. This variability is expected if a small number of loci explain most of the heterosis. The average level of heterosis was less than expected after eight generations of sib mating. This is most likely due to selection opposing the increase in homozygosity caused by inbreeding. The combination of these two imperfect correlations resulted in no significant correlation between genetic distance estimated from markers and heterosis. PMID- 24220964 TI - Chloroplast DNA variation in diploid and polyploid species of Bromus (Poaceae) subgenera Festucaria and Ceratochloa. AB - Chloroplast DNA (cpDNA) restriction endonuclease patterns are used to examine phylogenetic relationships between Bromus subgenera Festucaria and Ceratochloa. Festucaria is considered monophyletic based on the L genome, while Ceratochloa encompasses two species complexes: the B. catharticus complex, which evolved by combining three different genomes, and the B. carinatus complex, which is thought to have originated from hybridization between polyploid species of B. catharticus and diploid members of Festucaria. All species of subgenus Ceratochloa (hexaploids and octoploids) were identical in chloroplast DNA sequences. Similarly, polyploid species of subgenus Festucaria, except for B. auleticus, were identical in cpDNA sequences. In contrast, diploid species of subgenus Festucaria showed various degrees of nucleotide sequence divergence. Species of subgenus Ceratochloa appeared monophyletic and phylogenetically closely related to the diploid B. anomalus and B. auleticus of subgenus Festucaria. The remaining diploid and polyploid species of subgenus Festucaria appeared in a distinct grouping. The study suggests that the B. catharticus complex must have been the maternal parent in the proposed hybrid origin of B. carinatus complex. Although there is no direct evidence for the paternal parent of the latter complex, the cpDNA study shows the complex to be phylogenetically very related to the diploid B. anomalus of subgenus Festucaria. PMID- 24220965 TI - 5S-RNA genes of barley are located on the second chromosome. AB - The genes coding for 5S RNA in barley were cloned, sequenced, and their cluster was assigned to chromosome 2 using wheat-barley chromosome addition lines. High resolution gel-electrophoresis of DNA and subsequent hybridization revealed new details of the organization of 5S DNA both in wheat and barley. The in situ hybridization of the cloned 5S gene with triploid endosperm nuclei also suggests that these genes are located in a single locus. PMID- 24220966 TI - Metabolic complementation for a single gene function associated with partial and total loss of donor DNA in interspecific somatic hybrids. AB - We report here on the obtainment of interspecific somatic, asymmetric, and highly asymmetric nuclear hybrids via protoplast fusion. Asymmetric nuclear hybrids were obtained after fusion of mesophyll protoplasts from a nitrate reductase-deficient cofactor mutant of N. plumbaginifolia with irradiated (100 krad) kanamycin resistant leaf protoplasts of a haploid N. tabacum. Selection for nitrate reductase (NR) and/or kanamycin (Km) resistance resulted in the production of three groups of plants (NR(+), NR(+), Km(R), and NR(-)Km(R)). Cytological analysis of some hybrid regenerants showed the presence of numerous tobacco chromosomes and chromosome fragments, besides a polyploid N. plumbaginifolia genome (tetra or hexaploid). All the regenerants tested were male sterile but some of them could be backcrossed to the recipient partner. In a second experiment, somatic and highly asymmetric nuclear hybrids were obtained after fusion of mesophyll protoplasts from the universal hybridizer of N. plumbaginifolia with suspension protoplasts of a tumor line of N. tabacum. Selection resulted in two types of colonies: nonregenerating hybrid calli turned out to be true somatic hybrids, while cytological analysis of regenerants obtained on morphogenic calli did not show any presence of donor-specific chromosomes. Forty percent of the hybrid regenerants were completely fertile, while the others could only be backcrossed to the recipient N. plumbaginifolia. Since the gene we selected for is not yet cloned, we were not able to demonstrate the transfer of genetic material at the molecular level. However, since no reversion frequency for the nitrate reductase mutant is known, and due to a detailed cytological knowledge of both fusion partners, we feel confident in speculating that intergenomic recombination between N. plumbaginifolia and N. tabacum has occurred. PMID- 24220967 TI - Relative efficiency of selection methods to improve a ratio of two traits in Tribolium. AB - Three generations of upward selection for the egg mass/adult weight ratio were carried out in Tribolium castaneum. The experiment involved five lines: E - selected for increased egg mass; W - selected for decreased adult weight; R - selected for egg mass/adult weight directly; L - linear index selected with economic weights of m 2: -m 1 egg mass to adult weight (m 1 and m 2 are the means for adult weight and egg mass, respectively); NL - nonlinear index selected. Adult weight (7 days after adult emergence) and egg mass (between 7 and 11 days) were measured. The NL, E, and L lines had the greatest observed responses for the ratio; the R and W lines were not effective in improving the egg mass/adult weight ratio. It was expected that the NL line would be superior to the E, L, and R lines, and that the W line would respond the least. Observed response was significant for egg mass in the NL line, and for adult weight in the E, W, and R lines. Strong selection to increase egg mass seems to represent the optimal criterion for the ratio to be improved. The usefulness of nonlinear indices as selection criteria to improve a nonlinear trait, previously found to be optimal for a trait defined as the product of two component traits, appears to hold also for the selective improvement of the ratio of two traits. Serious limitations expected for direct selection of the ratio have been confirmed in this experiment. PMID- 24220968 TI - Identifying populations useful for improving parents of a single cross based on net transfer of alleles. AB - Theory and methods for identifying populations (P y ) with the highest frequency of favorable dominant alleles not present in an elite single cross (I 1* I 2) have been developed recently. During selection, new favorable alleles can be transferred from P y to either I 1 or I 2 only at the risk of losing favorable alleles already present in the single cross. A "net improvement" (NI) statistic, which estimates the relative number of favorable alleles that can be gained from P y minus the relative number of favorable alleles that can be lost from I 1 or I 2, is presented. NI is calculated as maximum [(I 1*P y -I 1*I 2)/2,(I 2*P y -I 1*I 2)/2]. Because I 1 * I 2 is constant in an experiment, the method reduces to choosing P y populations with the best mean performance in combination with either I 1 or I 2. For a set of maize (Zea mays L.) grain yield data, NI was highly correlated to three other statistics proposed for choosing populations, namely: (1) minimally biased estimate (l [Formula: see text]MU') of the relative number of favorable dominant alleles present in P y but not in I 1 and I 2; (2) minimum upper bound on l [Formula: see text]MU; and (3) predicted performance of the three-way cross [P y (I 1* I 2)]. While l [Formula: see text]MU' estimates potential improvement likely to be achieved only through long-term recurrent selection, NI is probably a better predictor of short-term improvement in single cross performance. PMID- 24220969 TI - Genetic and biochemical characterization of corn inbred lines tolerant to the sulfonylurea herbicide primisulfuron. AB - Inbred lines of corn (Zea mays L.) have been characterized, which exhibit differential sensitivity to the sulfonylurea herbicide primisulfuron (2-[3-(4,6 bis(di-fluoromethoxy) pyrimidin-2-yl)-ureidosulfonyl]-benzoic acid methylester). When treated postemergence with 160 g a.i. per hectare, inbred 4CO exhibited complete tolerance while inbred 4N5 was killed. The F1 hybrid 4C0 x 4N5 was uniformly tolerant indicating dominance of the tolerance trait. The field observations correlated with laboratory tests in which seedling root growth was measured. Based on IC50, inbred 4CO was more than ten times more tolerant than inbred 4N5. In the F2 and F3 generations, a 3?1 segregation of tolerant and sensitive individuals was observed, consistent with tolerance being inherited as a single dominant trait. Backcrosses of heterozygous F1 plants with the sensitive parent (4N5) yielded progeny that segreated at the expected 1?1 ratio. Backcrosses with 4C0 yielded tolerant offspring only. Inhibition characteristics of acetohydroxyacid synthase (AHAS; E.C. 4.1.3.18) were determined. The enzymes from both inbreds and their F1 hybrid were equally sensitive and strongly inhibited by primisulfuron (IC50: 7 nM). The fate of (14)C-labeled primisulfuron in seedling tissues of inbred 4C0 and the hybrid, 4C0 x 4N5, indicated rapid metabolism with a half-life (t 1/2) of approximately 3 h. On the other hand, the herbicide-sensitive inbred 4N5 was considerably slower to metabolize primisulfuron (t 1/2 >24 h). These data indicate that differential metabolism is the mechanism of tolerance to the sulfonylurea herbicide primisulfuron in tolerant corn. PMID- 24220970 TI - Progeny tests of barley, wheat, and potato regenerated from cell cultures after in vitro selection for disease resistance. AB - Because plant cells cultured in vitro express genetic variability and since they can be regenerated into functional plants, procedures have been designed to use this system for the production of plants with new important agronomic characteristics, particularly for disease resistance. For barley, wheat, and potato somaclones have been found that were less susceptible to a toxin of Helminthosporium, fusaric acid, Fusarium coeruleum, F. sulphureum, or Phytophthora infestans, when screened in the first in-vitro-derived generation. Here the progeny of such somaclones is evaluated after natural and artificial infection, using greenhouse-grown or field material. The progenies of the same somaclones did not express detectable differences, which indicated that no heterozygous mutations occurred. Most lines and clones differed in their level of susceptibility to the pathogen compared to the level of the starting material, but these data were in no instance significant. It is discussed here whether this lack of significance is due to a lack of genetic differences or whether the test procedures are in adequate for detecting and securing the slight, probably quantitative, alterations. PMID- 24220971 TI - The molecular basis of genetic diversity among cytoplasms of Triticum and Aegilops : 7. Restriction endonuclease analysis of mitochondrial DNAs from polyploid wheats and their ancestral species. AB - Many related species and strains of common wheat were compared by matching differences among their mitochondrial genomes with their "parent" nuclear genomes. We examined three species of Aegilops, section Sitopsis (Ae. bicornis, Ae. sharonensis, and Ae. speltoides), emmer wheat (Triticum dicoccoides, T. dicoccum, and T. durum), common wheat (T. spelta, T. aestivum, and T. compaction), and timopheevi wheat (T. araraticum, T. timopheevi, and T. zhukovskyi). A single source of the cytoplasm was used in all the species, except Ae. speltoides (two sources), T. araraticum (two), and T. aestivum (three). Following restriction endonuclease analyses, the mitochondrial genomes were found to comprise seven types, and a dendrogram showing their genetic relatedness was constructed, based upon the percentage of common restriction fragments. MtDNAs from T. dicoccum, T. durum, T. aestivum, and T. compactum yielded identical restriction fragment patterns; these differed from T. dicoccoides and T. spelta mtDNAs in only 2.3% of their fragments. The fragment patterns of T. timopheevi and T. zhukovskyi were identical, and these differed from T. araraticum mtDNA by only one fragment. In both the emmer-dinkel and timopheevi groups, mitochondrial genome differentiation is evident, suggesting a diphyletic origin of each group. MtDNAs from four accessions of the Sitopsis species of Aegilops differ greatly from one another, but those of Ae. bicornis, Ae. sharonensis, and Ae. searsii, belonging to the same subsection Emarginata, are relatively similar. MtDNAs of timopheevi species are identical, or nearly so, to those of Ae. speltoides accession (09), suggesting that the latter was the cytoplasm donor to the former, polyploid group. The origin of this polyploid group seems to be rather recent in that the diploid and polyploid species possess nearly identical mitochondrial genomes. We cannot determine, with precision, the cytoplasm donor to the emmer dinkel group. However, our results do suggest that mitochondrial DNAs show larger evolutionary divergence than do the ctDNAs from these same strains. PMID- 24220972 TI - Characterization of relic DNA from barley genome. AB - High-molecular-weight "relic" DNA fraction can be electrophoretically separated from the bulk of barley DNA digested with different restriction enzymes. We have cloned and analyzed a population of relic DNA fragments. The majority of AluI relic DNA clones contained barley simple sequence satellite DNA and other families of repetitive DNA. One of these families, designated HvRT, has been analyzed in detail. This family is composed of tandemly arranged 118-bp monomers and is present in 7 * 10(5) copies in the barley genome. Clones representing the HvRT family were sequenced. HvRT repeats were found to contain high levels of methylated cytosine. The HvRT family was found in the genomes of H. vulgare, H. leporinum, H. murinum, H. jubatum, but not in H. marinum, H. geniculatum, and wheat. Different barley species and cultivars show restriction fragment length polymorphism with the HvRT probe. Chromosome-specific subfamilies of HvRT were found to be present on different barley chromosomes, providing the possibility of using the HvRT probe as a chromosome specific marker. HvRT fragments up to 810 kbp in length were resolved by pulsed field gel electrophoresis. PMID- 24220973 TI - The value of gametoclonal variation in breeding for quantitative traits in flue cured tobacco (Nicotiana tabacum L.). AB - In tobacco (Nicotiana tabacum L.), anther-derived doubled haploid populations have been shown to exhibit large amounts of unexpected genetic variation and a severe depression in cured leaf yield when compared to conventionally inbred genotypes from comparable sources. A previous study had predicted that the yield depression observed in a doubled haploid population-derived from a near homozygous cultivar, NC95, might be overcome through a recurrent selection program. In the current study, progress from three cycles of full-sib family selection for improved yield in an anther-culture derived population of NC95 was measured, as well as the remaining genetic variation within the population. A design II experiment was conducted in the population following three cycles of selection. Results indicate that the NC95 yield level has been recovered in the third selection cycle population. Although most of the genetic variation in the population appears to be exhausted, the additive genetic variance among maternal half-sib families for yield is significant, and it appears that continued yield improvement can be made through recurrent selection. Significant additive-genetic variance for yield was found among maternal half-sib families but was essentially zero among the paternal half-sib families, suggesting that remaining genetic variation is not being transmitted through pollen. One possible explanation results from the phenomenon of DNA amplification that can occur during the anther culture process, and that may enable extraordinary recombinational events and reduce the viability of male gametes. PMID- 24220974 TI - Effect of different restriction enzymes, probe source, and probe length on detecting restriction fragment length polymorphism in tomato. AB - Since the construction and use of RFLP genetic maps depends on the ability of cloned sequences to detect polymorphism, we have attempted to determine conditions under which maximum levels of polymorphism can be detected. Forty cloned nuclear sequences from three different libraries (cDNA, EcoRI genomic, and Pstl genomic) were hybridized to total DNA from 149 plants representing eight species of the tomato genus Lycopersicon. Five different restriction enzymes were employed in this study. We examined the relationship between polymorphism (number of restriction patterns) and clone size, restriction enzyme, size of hybridizing restriction fragments, and clone source (library). We found no relationship between clone size (ranging from 0.4 to 5.3 kb) and polymorphism. There was a strong positive relationship (r (2) = 0.79) between polymorphism and the average size of the fragments produced by each restriction enzyme. cDNA clones hybridized to larger fragments compared to genomic clones. cDNAs also detected significantly more polymorphism (approximately 25% more) than genomic clones - possibly indicating high levels of sequence variability in introns and/or areas flanking coding regions. PMID- 24220975 TI - Somaclonal variant UC-T3: the expression of Fusarium wilt resistance in progeny arrays of celery, Apium graveolens L. AB - First generation (S1) progeny, second generation (S2) progeny, and backcross (BC) progeny of a celery (Apium graveolens L. var. dulce) somaclonal variant, UC-T3, were evaluated for resistance to the fungus Fusarium oxysporum f. sp. apii, race 2 (FOA2). Chisquare analysis of S1 progeny showed that the expression of resistance did not fit a single-locus model. S2 progeny means were similar among families, except in a heavily infested field. The lowest ranking S2 family in both the lightly infested and heavily infested fields was significantly more resistant to FOA2 than individuals of the susceptible progenitor line 'Tall-Utah 527OR'; therefore; it was concluded that the trait was heritable. The phenotypic distribution of the backcross progeny was broad, suggesting that the new resistance was conferred by at least two genes whose expression was dominant to susceptibility. The mean scores for disease resistance of the progeny of crosses between UC-T3 and the moderately resistant line, 'Tall-Utah 527OHK', generally equaled the resistance found among the progeny of the most resistant parent. PMID- 24220976 TI - Genomic DNA can be used with cationic methods for highly efficient transformation of maize protoplasts. AB - Efficient delivery of genomic DNA fragments to maize protoplasts was obtained by new methods using the polycation Polybrene or Lipofectin cationic liposomes. Stable kanamycin-resistant secondary transformants were recovered after transfection with genomic DNA from a maize cell line that had previously been tagged with the bacterial gene neomycin phosphotransferase (nptII) in a first round transformation. The frequency of secondary transformants with nptII homologous DNA sequences was 3% or 6% of all randomly picked microcalli after Polybrene or Lipofectin-mediated transfection, respectively. Transformation with genomic DNA by these methods may allow easy transfer of uncloned genes encoding desirable characteristics to crop species that can be regenerated from protoplasts. PMID- 24220977 TI - Predominance and tissue specificity of adenine methylation in rice. AB - Using 'A' and 'C' methylation-specific restriction enzymes, namely, MboI, Sau3AI, DpnI, MspI, and HpaII, total rice cv Basmati 370 DNA, repetitive DNAs, and a specific repeat sequence indicated an abundance of adenine methylation. Although cytosine methylation in 5'-CCGG-3' sequences suggested more CpC methylation than CpG, the 'C' methylation in sequence 5'-GATC-3' was comparatively less than 'A' methylation. Furthermore, the presence of adenine methylation was tissue specific; it was predominant in rice shoot DNA as compared to embryo DNA. This pattern was also observed in two other cultivars of rice, i.e., R-24 and Sona, and was again confirmed using a cloned probe of a specific repeat sequence. Besides the changes in adenine methylation, there was also a qualitative change in 5mC from CpG to CpC dinucleotides in these two tissue systems. PMID- 24220978 TI - The expression and perpetuation of inherent somatic variation in regenerants from embryogenic cultures of Pennisetum glaucum (L.) R. Br. (pearl millet). AB - Genetic analysis was conducted on the qualitative and quantitative traits of sexual progeny derived from embryogenic cultures of two inbred lines of Pennisetum glaucum (L.) R. Br. (pearl millet). These lines included a genetically stable inbred of Tift 23 BE and a genetic marker line, derived from Tift 23BE, which bore qualitative genetic markers for a dominant purple plant trait (P) and two recessive traits, early flowering (e1) and yellow stripe (ys). Tissue culture regenerant populations (R0) and progeny populations (R1) produced from these plants by selfing showed no qualitative genetic variation when derived from the genetically stable inbred Tift 23BE. In contrast, stably inherited qualitative variation for a number of genetic markers was observed in R0, R1, and R2 progeny of the genetic marker line. In a population of 1,911 plants regenerated over a 12 month period, 0.02% of the population lost or showed reduced expression of the purple plant trait and 92% of plants were chlorophyll deficient. Plants showing reduction or loss of anthocyanin synthesis also flowered later. None of the purple plants showed any significant variation in flowering time. The incidence of chlorophyll deficiency increased with time in culture, 51 % of the progeny regenerated after 1 month were chlorophyll deficient, while 100% of the plants regnerated after 12 months were chlorophyll deficient. Qualitative variation was also observed in control populations of the genetic marker line where 1 plant in a total of 1,010 lacked purple pigmentation and a total of 6% showed chlorophyll variation in the first generation (S0). The presence of qualitative variation in controls suggests that the inherent variation present in the original explant was expressed and perpetuated in vitro. Quantitative variation was observed for a number of traits in the first sexual cycle (R1) of the marker line but did not occur in a subsequent generation, suggesting that this variation was epigenetic. PMID- 24220979 TI - Iron-deficiency chlorosis evaluation of soybean with tissue culture. AB - The objectives of this study were: (i) to develop a tissue culture technique for the evaluation of Fe efficiency in soybean, and (ii) to compare the laboratory technique with field Fe chlorosis scores. Nineteen genotypes that had low and high levels of Fe efficiency were evaluated in the laboratory and at five field locations. Friable callus was induced from epicotyl sections, weighed, and placed on two different modified Murashige and Skoog media; one low in alpha naphthaleneacetic acid and the other low in Fe. Callus growth was rated as lack of growth compared to respective controls. As an example, Fe-inefficient cultivars ('Asgrow A3205' and 'Pride B216') had significantly reduced growth compared to Fe-efficient germ plasm lines ('All' and 'A14'). Correlation between the laboratory and field chlorosis rating was highest for the low auxin medium (r (2) = 0.78), although correlation for the low Fe medium was also significant (r (2) = 0.72). These results show that in vitro evaluation for Fe efficiency can be a useful tool for plant breeders. PMID- 24220980 TI - Intergeneric transfer of cytoplasmic male sterility between Raphanus sativus (cms line) and Brassica napus through cytoplast-protoplast fusion. AB - Cytoplasts isolated from hypocotyl protoplasts of Raphanus sativus cv Kosena (cms line) by ultracentrifugation through Percoll/mannitol discontinuous gradient were fused with iodoacetamide(IOA)-treated protoplasts of Brassica napus cv Westar. Seventeen randomly selected regenerated plants were characterized for morphology and chromosome numbers. All of the regenerated plants had morphology identical to B. napus and 10 of them possessed the diploid chromosome number of B. napus. The remaining plants had chimeric or aneuploid chromosome numbers. The mitochondrial genomes in the 10 fusion products possessing the diploid chromosome numbers of B. napus were examined by Southern hybridization analysis. Four of the 10 plants contained mitochondrial DNA showing novel hybridization patterns. Of these 4 plants, 1 was male sterile, and 3 were male fertile. The remaining plants showed mitochondrial DNA patterns identical to B. napus and were male fertile. PMID- 24220981 TI - Long-term strategy for the statistical design of a forest health monitoring system. AB - A conceptual framework is given for a broad-scale survey of forest health that accomplishes three objectives: generate descriptive statistics; detect changes in such statistics; and simplify analytical inferences that identify, and possibly establish cause-effect relationships. Our paper discusses the development of sampling schemes to satisfy these three objectives, but without any design restrictions implied by existing sample surveys. A general vision of a desirable future system will increase chances that short-term decisions will lead to better environmental monitoring systems in the long term. PMID- 24220982 TI - Patchy distributions: Optimising sample size. AB - A method for estimating sample size which does not require an a priori definition of desired precision, or the assumption that the population is normally distributed with constant variance, has recently been proposed. This paper discusses this method and presents five modifications which make the method easier to use and reduce the probability of estimating a larger sample size than is actually required. The method is extended and used to estimate the mean abundance of patchily distributed benthic organisms. The technique can be used to guide the design of any environmental sampling programme, be it physical, chemical or biological, where comparisons between times and/or locations are required. Trade-offs between numbers of replicates and numbers of levels/sites are discussed. PMID- 24220983 TI - Air quality monitoring for multiple pollutants: Optimization of a network around a hypothetical potash plant and two thermal power stations in open countryside. AB - A method is presented for the design of multi-pollutant air quality monitoring networks (AQMN). This technique leads to an optimal network, i.e. a network providing a maximum of information with a minimum of measurement devices. The spatial correlation analysis technique is used to compare the information given by the potential sites that may form the network. The concept of potential of violation is defined to take into account the number of times that the maximum emission values tolerated by law are exceeded. Both objectives are weighted automatically through an adjustable parameter, b, for which an estimation procedure has been developed in this study, depending on the purpose of the network. Several methods are described, allowing simultaneous consideration of different pollutants. As an illustration of these methods, a number of air quality monitoring networks is designed to perform an analysis of the environmental impact due to a hypothetical potash processing plant and two thermal power stations. PMID- 24220984 TI - Organochlorine contaminant concentrations in caddisfly adults (Trichoptera) collected from great lakes connecting channels. AB - Pennsylvania-style light traps were used to capture adult Trichoptera from the St. Marys, St. Clair, Detroit and Niagara rivers, Canada. Adequate biomass was acquired in single, 2-h collections to permit triplicate gas chromatographic analyses of 1-4 g samples for 36 organochlorine contaminants. Contaminant levels varied unpredictably but relatively little among samples taken at monthly intervals over the summer. Samples collected simultaneously from the two sides of the Detroit R. reflected local sediment contaminant patterns, suggesting limited dispersal by adults. Genus-specific differences in contaminant concentrations within the Hydropsychidae and Leptoceridae probably reflect differences in larval habitats and manner of feeding. Contaminant concentrations and relative composition paralleled published reports of contaminants in sediments from collection locations. St. Marys R. caddisflies contained contaminant levels indistinguishable from samples collected at reference sites. St. Clair R. samples contained high levels of compounds associated with petrochemical industries located in the river's upstream reaches. High levels of polychlorinated biphenyls (PCBs) and most other contaminants in Detroit R. samples reflected industrial loadings near Detroit, Michigan. Niagara R. samples contained elevated concentrations of PCBs and pesticides. Cluster analysis grouped samples into five clusters each with unique contaminant composition. These also corresponded to geographic origin: St. Marys, St. Clair, Detroit and upper and lower Niagara rivers. The relative ease of collection and consistent results obtained render adult Trichoptera potentially valuable candidates for surveys of aquatic contamination over a broad range of geographical and ecological conditions. PMID- 24220985 TI - Development of the hypophysis of the arctic lamprey, Lampetra japonica. AB - The hypophysis of early larval stages, from the moment of hatching on the 18th day after fertilization to the 101st day of larval life, of the arctic lamprey Lampetra japonica was studied with scanning and transmission electron microscopes. A solid cord of cells of the distal part of the nasopharyngeal duct represents the early adenohypophysis. On the 20th day after fertilization, several of the epithelial cells of this structure showed first indications of secretory activity with an extensive Golgi apparatus and small electron-dense secretory granules. On the 26th day, non-secretory, stellate (=supporting) cells and secretary cells can be distinguished. Already on the 39th day, two different parts can be distinguished in the adenohypophysis: the pars distalis with cells containing small dense granules, and the pars intermedia with cells containing larger granules of medium density. The number of granulated cells increases steadily; on the 101st day two pars distalis cell types can be distinguished. The neurohypophysis consists of a thin anterior and a thick posterior part. Already on the 20th day single nerve terminals in the ependymal layer of the diencephalic (=infundibular) floor contain dense elementary granules. The number of granule containing terminals increases steadily; on the 101st day almost all terminals contain granules. The present observations suggest an early secretory function of the lamprey hypophysis. PMID- 24220986 TI - Neuroendocrine control of reproduction in lampreys. AB - In most vertebrate classes, the hypothalamus and pituitary have well-defined roles in the control of reproduction. Until recently, there was little evidence for neuroendocrine control of reproduction in lampreys, one of the only two living representative groups of the oldest lineage of vertebrates, the Agnathans. The question whether there is hypothalamic control over reproduction has special significance since these fishes, with the hagfishes, are modern descendants of the most primitive vertebrates available for study. This paper summarizes the studies on the structure and function of lamprey GnRH which provide evidence for the regulatory influence of the hypothalamus on the pituitary-gonadal axis. These data imply that evolution of this mechanism most likely antedated the origin of all known vertebrates. PMID- 24220987 TI - The role of external and internal factors during the phase of reproduction in lampreys, with special regard to the interplay between gonadal and extragonadal (interrenal) steroids. PMID- 24220988 TI - Morphogenesis of somatostatin- and insulin-secreting cells in the lamprey endocrine pancreas. AB - The development of the endocrine pancreatic tissue during the entire life cycle of lampreys was provided through a review of previous literature and through a description of new, preliminary immunohistochemical data on a number of species. There seems to be no firm conclusions on the method of development of the endocrine pancreas during embyrogenesis, but observations of 79-day old larvae suggest that somatostatin-positive cells are confined to the epithelium of the alimentary canal, which is also the site at which insulin-immunoreactive islets form. This type of cellular distribution and morphogenesis at the oesophago intestinal junction continues throughout the larval period. In northern hemisphere species, a caudal pancreatic mass forms at metamorphosis from the transformed epithelium of the bile duct. Evidence is presented to suggest that the process of bile duct degeneration and transformation is highly synchronized and that interference with the morphogenetic event will alter the normal distribution of pancreatic islets in the adult. The position of the bile duct in larvae of southern hemisphere species results in no caudal pancreas in adults. The adult cranial pancreas of all lamprey species, forms from remnants of the larval islets and through proliferation of new islets from the epithelium of the developing intestinal diverticulum. In holarctic lampreys, the cranial and caudal masses are connected by a discontinuous intermediate cord of islets and all three regions contain equal numbers of somatostatin- and insulin-immunoreactive cells. Following metamorphosis, growth of the caudal pancreas occurs through cellular proliferation from within but the cranial pancreas continues to recruit islets from the diverticular epithelium through the upstream-migrant (prespawning) period. PMID- 24220989 TI - Gut hormones in cyclostomes. AB - The current state of knowledge about regulatory peptides in endocrine cells and nerves of the alimentary canal of lampreys and hagfishes is reviewed. Cyclostomes have a wide range of peptides similar immunochemically to those of higher vertebrates. They include, in the endocrine cells of the intestine, peptides resembling glucagon, gastrin/cholecystokinin, peptide YY (pancreatic polypeptide/neuropeptide Y), substance P, vasoactive intestinal peptide, somatostatin and, in the larval stages at least, insulin. The enteric nerves of some lamprey species contain peptides resembling bombesin (gastrin-releasing peptide) and calcitonin gene-related peptide, as well as serotonin. The occurrence of other peptides is less well documented.Little is known of the molecular structure or the biological roles of the enteric peptides in cyclostomes. Extraction, purification, sequencing and physiological experiments are greatly needed. PMID- 24220990 TI - Seasonal and estradiol-17beta-stimulated changes in thyroid function of adult Geotria australis, a southern hemisphere lamprey. AB - Measurable in vitro hepatic monodeiodinase activity of the southern hemisphere lamprey, Geotria australis, was present only during the first 5 of the 16 month upstream spawning migration of this species. The production of T3 from T4 in vitro was pH-sensitive, and exhibited typical Michaelis-Menton kinetics. No consistent differences in the serum T4 concentrations were found in animals sampled at different times during the period of their residence in fresh water. However, serum T3 concentrations underwent a progressive decline during this period. Estradiol-17beta (E2), administered as a suspension in hydrogenated coconut oil, induced a lowering of serum T4 concentrations and a rise in serum T3:T4 ratios, but had no measureable effect on liver size and serum concentrations of total calcium and protein. In the males, E2 induced the production of a small amount of a serum protein assumed to be vitellogenin, but there was no conspicuous increase in the amount of the same protein in females. This response to E2-challenge parallels more closely that of cyprinids than that of salmonids. PMID- 24220991 TI - Xanthine derivatives quantification in serum by capillary zone electrophoresis. AB - A capillary electrophoresis method was developed to quantify caffeine and theophylline, xanthine derivatives with bronchodilator activity. Buffer concentration, pH and applied voltage were optimized using a central composite design-face centred. Separation conditions were: silica capillary tube, 75 MUm (i.d.) and 61 cm (total length); absorbance detection, 280 nm; borate buffer, 20 mM, pH 9.0; applied voltage, 25 kV and 1 psi injection/8 s. Validation was performed in blank serum following the International Conference Harmonization guidelines: resolution (peaks without overlapping), linear range (0.125-50 ug/mL; r(2) > 0.9999), limits of detection and quantification (10; 20 and 33; 66 ppb for caffeine and theophylline, respectively), intra- and inter-day precision (Relative standard deviation lower than 1.9%) and accuracy (98-101%). Migration times were <8 min. This method is simple, specific and suitable and reaches high label claims (98.7-100.4%) in pharmaceutical formulations analysis. Moreover, the method was applied to the monitoring of the analytes in serum of patients. PMID- 24220992 TI - Purification of two triterpenoids from Schisandra chinensis by macroporous resin combined with high-speed counter-current chromatography. AB - A method for preparative purification of corosolic acid and nigranoic acid from Schisandra chinensis (SC) was established using a combination of macroporous absorption resin column separation and high-speed counter-current chromatography (HSCCC). The crude extracts obtained from SC using 70% ethanol were separated on a macroporous resin column and then eluted with a graded ethanol series. The 70% ethanol fraction was used as the sample for separation of the two triterpenoids by HSCCC. The two-phase solvent system used for HSCCC separation was chloroform-n butanol-methanol-water (10:0.5:7:4, v/v/v/v). The upper phase was used as the stationary phase of HSCCC. Corosolic acid (16.4 mg) of 96.3% purity and nigranoic acid (9.5 mg) of 98.9% purity were obtained in a one-step HSCCC separation from 100 mg of the sample. The structures of corosolic acid and nigranoic acid were identified by (1)H-nuclear magnetic resonance (NMR) and (13)C-NMR. PMID- 24220993 TI - Monte carlo studies of electronic processes in dye-sensitized solar cells. AB - This topic reviews random walk Monte Carlo simulation models of charge transport in DSSC. The main electron transport approaches used are covered. Monte Carlo methods and results are explained, addressing the continuous time random walk model developed for transport in disordered materials in the context of the large number of trap states present in the electron transporting material. Multiple timescale MC models developed to look at the morphology dependence of electron transport are described. The concluding section looks at future applications of these methods and the related MC models for polymer blend cells. PMID- 24220994 TI - Dispersion corrected hartree-fock and density functional theory for organic crystal structure prediction. AB - We present and evaluate dispersion corrected Hartree-Fock (HF) and Density Functional Theory (DFT) based quantum chemical methods for organic crystal structure prediction. The necessity of correcting for missing long-range electron correlation, also known as van der Waals (vdW) interaction, is pointed out and some methodological issues such as inclusion of three-body dispersion terms are discussed. One of the most efficient and widely used methods is the semi classical dispersion correction D3. Its applicability for the calculation of sublimation energies is investigated for the benchmark set X23 consisting of 23 small organic crystals. For PBE-D3 the mean absolute deviation (MAD) is below the estimated experimental uncertainty of 1.3 kcal/mol. For two larger pi-systems, the equilibrium crystal geometry is investigated and very good agreement with experimental data is found. Since these calculations are carried out with huge plane-wave basis sets they are rather time consuming and routinely applicable only to systems with less than about 200 atoms in the unit cell. Aiming at crystal structure prediction, which involves screening of many structures, a pre sorting with faster methods is mandatory. Small, atom-centered basis sets can speed up the computation significantly but they suffer greatly from basis set errors. We present the recently developed geometrical counterpoise correction gCP. It is a fast semi-empirical method which corrects for most of the inter- and intramolecular basis set superposition error. For HF calculations with nearly minimal basis sets, we additionally correct for short-range basis incompleteness. We combine all three terms in the HF-3c denoted scheme which performs very well for the X23 sublimation energies with an MAD of only 1.5 kcal/mol, which is close to the huge basis set DFT-D3 result. PMID- 24220996 TI - Nodal combined blue nevus and benign nevus cells in multiple axillary sentinel nodes in a patient with breast carcinoma: report of a case. AB - Combined blue nevus and benign nevus cells were identified in the same sentinel lymph node. Blue nevus alone was also present in an additional sentinel lymph node in the same axilla in a patient who underwent needle localization, wide local excision, and sentinel lymph node biopsy for her pT1cN1mi(sn)M(na) invasive duct carcinoma of the breast. Of the 4 sentinel lymph nodes, 1 showed micrometastasis and 2 other lymph nodes showed blue nevus involving the capsule and trabeculae of the nodes. The patient had no significant previous clinical history of any skin tumors and had a negative clinical examination for malignant melanoma or pigmented skin lesions after the diagnosis of nodal blue nevus. To our knowledge, this is the first case report of combined blue nevi involving multiple sentinel lymph nodes in the same axilla. An equally interesting finding is the presence of benign nonpigmented nevus cells in continuation with the blue nevus in the same node. PMID- 24220995 TI - Neurological damage in MSUD: the role of oxidative stress. AB - Maple syrup urine disease (MSUD) is a metabolic disease caused by a deficiency in the branched-chain alpha-keto acid dehydrogenase complex, leading to the accumulation of branched-chain keto acids and their corresponding branched-chain amino acids (BCAA) in patients. Treatment involves protein-restricted diet and the supplementation with a specific formula containing essential amino acids (except BCAA) and micronutrients, in order to avoid the appearance of neurological symptoms. Although the accumulation of toxic metabolites is associated to appearance of symptoms, the mechanisms underlying the brain damage in MSUD remain unclear, and new evidence has emerged indicating that oxidative stress contributes to this damage. In this context, this review addresses some of the recent findings obtained from cells lines, animal studies, and from patients indicating that oxidative stress is an important determinant of the pathophysiology of MSUD. Recent works have shown that the metabolites accumulated in the disease induce morphological alterations in C6 glioma cells through nitrogen reactive species generation. In addition, several works demonstrated that the levels of important antioxidants decrease in animal models and also in MSUD patients (what have been attributed to protein-restricted diets). Also, markers of lipid, protein, and DNA oxidative damage have been reported in MSUD, probably secondary to the high production of free radicals. Considering these findings, it is well-established that oxidative stress contributes to brain damage in MSUD, and this review offers new perspectives for the prevention of the neurological damage in MSUD, which may include the use of appropriate antioxidants as a novel adjuvant therapy for patients. PMID- 24220997 TI - Combined mesothelial cyst and lymphangioma of the small bowel: a distinct hybrid intra-abdominal cyst. AB - Intra-abdominal cysts have a variety of origins, of which lymphatic and mesothelial types are the most commonly encountered. Here we describe a combined mesothelial cyst and lymphangioma arising within the small bowel subserosa of an 80-year-old woman. This was found incidentally at laparotomy performed for an unrelated condition. To date, such a hybrid lesion has not been previously reported. The ways by which this lesion might have arisen are discussed. PMID- 24220998 TI - Fibroblastic Reticulum Cell Tumor of Spleen: A Case Report. AB - Fibroblastic reticulum cells (FBRCs) belong to a major subtype of stromal support cells in the lymphoid system and rarely give rise to tumors. We report a case of fibroblastic reticulum cell tumor arising in the spleen. The tumor was clinically and radiologically mistaken for a metastatic deposit in the spleen. Microscopically the tumor was composed of spindle cells arranged in fascicles and storiform pattern. The cells had oval to elongated vesicular nuclei and pale eosinophilic cytoplasm with indistinct cell borders. There were admixed inflammatory cells, including large numbers of plasma cells. The tumor cells were positive for smooth muscle actin, desmin, AE1/AE3, and MNF116. They were negative for S100, CD1a, CD21, CD23, CD34, CD31, and CD35 among other markers. The morphological features and immunoprofile of this rare tumor in comparison to the few cases reported in the literature are discussed along with the positive reaction with cytokeratins and their relationship to the smaller subset of FBRCs, the cytokeratin-positive interstitial reticulum cells in the spleen. PMID- 24220999 TI - Genetic variability for esterase enzyme in Onobrychis species. AB - Understanding polymorphism at the enzyme level is basic to its use in population and genetic studies. However, no such information is available on the variability among different sainfoin (Onobrychis) species. Therefore, our objective was to study the existence of genetic polymorphism for esterase in 17 Onobrychis species and three cultivars of O. viciifolia Scop. Three regions of banding were observed in all the materials tested, with the number of bands varying from 0 to 3, 3 to 14, and 1 to 2 bands in each of these zones, which have been designated EST1, EST2, and EST3 respectively. All the materials studied had unique banding patterns, the only common feature being that all of them, except one species, had isozyme 1. Identification was possible only for four species (O. iberica, O. kachetica, O. transcaucasica, and O. bieberstenii) and one cultivar ('Nova') based on the banding patterns. Large diversity was evident from the wide range of percent similarity values (0%-79%). Subsequent studies should be directed in using these isozyme banding patterns as markers to the desirable agronomic and quality traits of different germplasm lines. PMID- 24221000 TI - RFLP analysis of phylogenetic relationships and genetic variation in the genus Lycopersicon. AB - Forty single-copy, nuclear probes of known chromosomal position were used to examine restriction fragment length polymorphism in the tomato genus Lycopersion. The probes were from three libraries: one cDNA, and two genomic libraries [Symbol: see text]ne genomic made with EcoRI and the other with PstI. Total DNA from 156 plants representing eight species was cut with five different restriction enzymes and scored in 198 probe-enzyme combinations. Genetic distances between accessions (populations) and species were calculated from the resultant restriction patterns and proportion of shared bands. Accessions belonging to the same species largely clustered together, confirming their current classification. However, one mountain accession, classified as L. peruvianum var. humifusum (LA2150), was sufficiently distinct from the other accessions of L. peruvianum that it may qualify as a separate species L. esculentum and L. pimpinellifolium were the least clearly differentiated, possibly reflecting introgressive hybridization, known to have been promoted by man in recent history. Dendrograms constructed from cDNA versus genomic clones were nearly identical in their general grouping of species. The dendrograms revealed two major dichotomies in the genus: one corresponding to mating behavior [self-compatible (SC) versus self-incompatible (SI) species] and the other corresponding to fruit color (red versus green-fruited species). The ratio of withinversus between-accession diversity was much lower for SC species, indicating that most of the diversity within these species exists between populations, rather than within populations. Overall, the amount of genetic variation in the SI species far exceeded that found in SC species. This result is exemplified by the fact that more genetic variation could be found within a single accession of one of the SI species (e.g., L. peruvianum) than among all accessions tested of any one of the SC species (e.g., L. esculentum or L. pimpinellifolium). Results from this study are discussed in relationship to germ plasm collection/utilization and with regard to the use of RFLPs in tomato breeding and genetics. PMID- 24221001 TI - Transformation of Brassica napus canola cultivars with Arabidopsis thaliana acetohydroxyacid synthase genes and analysis of herbicide resistance. AB - A survey of selected crop species and weeds was conducted to evaluate the inhibition of the enzyme acetohydroxyacid synthase (AHAS) and seedling growth in vitro by the sulfonylurea herbicides chlorsulfuron, DPX A7881, DPX L5300, DPX M6316 and the imidazolinone herbicides AC243,997, AC263,499, AC252,214. Particular attention was given to the Brassica species including canola cultivars and cruciferous weeds such as B. kaber (wild mustard) and Thlaspi arvense (stinkweed). Transgenic lines of B. napus cultivars Westar and Profit, which express the Arabidopsis thaliana wild-type AHAS gene or the mutant gene csr1-1 at levels similar to the resident AHAS genes, were generated and compared. The mutant gene was essential for resistance to the sulfonylurea chlorsulfuron but not to DPX A7881, which appeared to be tolerated by certain Brassica species. Cross-resistance to the imidazolinones did not occur. The level of resistance to chlorsulfuron in transgenic canola greatly exceeded the levels that were toxic to the Brassica species or cruciferous weeds. Direct selection of transgenic lines with chlorsulfuron sprayed at field levels under greenhouse conditions was achieved. PMID- 24221002 TI - Genetic studies of corn (Zea mays L.) anther culture response. AB - Anthers of two maize (Zea mays L.) inbred lines, DBTS (P1) and B73 (P2), their F1, F2 and first backcross generations - F1 x DBTS (B1), and F1 x B73 (B2) - were float cultured in YP medium to study the inheritance of corn anther culturability using generation mean analysis. Significant effects of generation were observed for the three traits measured: anther response (%), frequency of embryos (%) and anther productivity. Variation among the generations was similar for anther response and frequency of embryos: no significant differences were found among the P1, F1, F2 and B1 means, but the means of P2 and B2 were significantly lower than those of the other generations. For anther productivity, the F2 generation tended to have a slightly higher tendency for multiple embryo formation. A simple additive-dominance model was adequate in explaining the inheritance of anther response and frequency of embryos, but digenic epistasis (additive x dominance) was involved in the inheritance of anther productivity. Additive genetic variance was higher than non-additive genetic variance for all the traits; however, only environmental variance was significant. Narrow-sense heritability estimates were 65% and 75% for anther response and frequency of embryos, respectively. Significant inter-plant variation was observed within generations, even for the inbred line DBTS, but isozymic analysis involving five enzyme loci did not reveal any genotypic variability within the inbred lines DBTS and B73. PMID- 24221003 TI - Fatty acid inheritance in microspore-derived Populations of spring rapeseed (Brassica napus L.). AB - The inheritance of major fatty acids in seed triglycerides was studied in three homozygous microspore-derived populations of spring rapeseed (Brassica napus L.). Crosses were made among parents with contrasting amounts of erucic, oleic, linoleic and linolenic acids. Microspores from F1 plants were cultured, and haploid plants were colchicine-doubled to provide homozygous populations reflecting F1 gametic arrays for fatty acid genotypes. Segregation ratios of the gametic arrays for specific fatty acid contents were compared to hypothetical models by the Chi-square test. Segregation pattern confirmed that erucic acid levels were controlled by two major loci, each having two alleles with additive effects. Oleic acid segregation indicated control of accumulation by at least two segregating genetic systems, one acting on chain elongation and the other involving desaturation. Accumulations of erucic acid and oleic acid were influenced by the same two loci, which control the chain elongation steps leading from oleic acid to erucic acid. Oleic acid was further influenced by at least two additional segregating loci involved in control of desaturation of oleic acid to form linoleic acid. Segregating alleles at loci involved in desaturation had a much smaller influence on oleic acid content than alleles segregating at loci controlling, the elongation of oleic acid to erucic acid. In a population free of erucic acid, the segregation pattern of linoleic acid levels fit a model involving segregating alleles at two loci. In contrast, segregation for linolenic acid content fits a three-locus additive model. In this study, microspore culture technology provided a rapid method of defining F1 gametic segregation for inheritance analyses. PMID- 24221004 TI - Genetic evaluation of haploid clonal lines of a single donor plant of Populus maximowiczii. AB - Haploid clonal lines derived from anthers of a single donor plant of Populus maximowiczii were evaluated for several quantitative traits. In a nursery test, variances due to clonal lines ranged from 8% to 12% of the phenotypic variance in growth cessation and flushing date, respectively. No variance in relative shoot growth rate was associated with clonal lines. In a greenhouse study, gametoclonal variance in several leaf morphology traits ranged from 9% to 37% of the total variance. In relative wood density, variation due to haploid lines accounted for 25% of the total variance. In an isozyme analysis of 20 haploid and dihaploid plants, significant non-Mendelian segregation in isocitrate dehydrogenase was detected. The implications of these results for tree breeding are discussed. PMID- 24221005 TI - Efficient gene introduction into rice by electroporation and analysis of transgenic plants: use of electroporation buffer lacking chloride ions. AB - We have developed a method for reproducibly obtaining transgenic rice at a high frequency (10(-4)): electroporation with a buffer in which chloride ions are replaced with organic acids. Co-transformation frequencies of the beta glucuronidase (GUS) and hygromycin phosphotransferase (HPT) genes located on two separate plasmids were higher than 50%. Transgenic rice plants contained multiple copies of introduced genes integrated into their genomes in a complex manner. GUS enzyme activity was not proportional to gene copy number. Introduced HPT genes were detected and expressed in the progeny of transformants. PMID- 24221006 TI - Asymmetric hybridization between Nicotiana tabacum and N. repanda by donor recipient protoplast fusion: transfer of TMV resistance. AB - Genetically asymmetric hybrids were recovered by fusion of Nicotiana tabacum protoplasts with irradiated protoplasts of kanamycin-resistant, nopalineproducing plants of N. repanda. Hybrid calli were selected by culture on media containing kanamycin and were regenerated. These plants were morphologically similar to N. tabacum but produced nopaline, indicating they retained genes from N. repanda. Esterase isozyme profiles also indicated that the plants are somatic hybrids, but are more similar to N. tabacum than N. repanda. Chromosome counts showed most of the hybrids had 55-62 chromosomes, which is consistent with extensive, although incomplete elimination of N. repanda chromosomes. The hybrids were largely male sterile, but about half of them set seed when crossed with N. tabacum. Chromosome numbers of the progeny and the pattern of inheritance of kanamycin resistance indicated the continued elimination of N. repanda genetic material in these backcrosses. The N. repanda parent used in these fusions gave a hypersensitive response to TMV, whereas the N. tabacum parent was TMV sensitive. When inoculated with TMV, plants from two hybrid clones gave a hypersensitive response. Plants from the other clones became systemically infected with the virus. PMID- 24221007 TI - Genetic diversity for restriction fragment length polymorphisms and heterosis for two diallel sets of maize inbreds. AB - Changes that may have occurred over the past 50 years of hybrid breeding in maize (Zea maize L.) with respect to heterosis for yield and heterozygosity at the molecular level are of interest to both maize breeders and quantitative geneticists. The objectives of this study were twofold: The first, to compare two diallels produced from six older maize inbreds released in the 1950's and earlier and six newer inbreds released during the 1970's with respect to (a) genetic variation for restriction fragment length polymorphisms (RFLPs) and (b) the size of heterosis and epistatic effects, and the second, to evaluate the usefulness of RFLP-based genetic distance measures in predicting heterosis and performance of single-cross hybrids. Five generations (parents, F1; F2, and backcrosses) from the 15 crosses in each diallel were evaluated for grain yield and yield components in four Iowa environments. Genetic effects were estimated from generation means by ordinary diallel analyses and by the Eberhart-Gardner model. Newer lines showed significantly greater yield for inbred generations than did older lines but smaller heterosis estimates. In most cases, estimates of additive x additive epistatic effects for yield and yield components were significantly positive for both groups of lines. RFLP analyses of inbred lines included two restriction enzymes and 82 genomic DNA clones distributed over the maize genome. Eighty-one clones revealed polymorphisms with at least one enzyme. In each set, about three different RFLP variants were typically found per RFLP locus. Genetic distances between inbred lines were estimated from RFLP data as Rogers' distance (RD), which was subdivided into general (GRD) and specific (SRD) Rogers' distances within each diallel. The mean and range of RDs were similar for the older and newer lines, suggesting that the level of heterozygosity at the molecular level had not changed. GRD explained about 50% of the variation among RD values in both sets. Cluster analyses, based on modified Rogers' distances, revealed associations among lines that were generally consistent with expectations based on known pedigree and on previous research. Correlations of RD and SRD with f1 performance, specific combining ability, and heterosis for yield and yield components, were generally positive, but too small to be of predictive value. In agreement with previous studies, our results suggest that RFLPs can be used to investigate relationships among maize inbreds, but that they are of limited usefulness for predicting the heterotic performance of single crosses between unrelated lines. PMID- 24221008 TI - Multivariate analysis of polypeptide synthesis in field-grown maize inbreds and hybrids. AB - A leaf disc method is described to permit the localized incorporation of (35)S-L methionine into polypeptides synthesized in individual leaves of maize plants grown in the field. The method of incorporation employs minimal external manipulation of the intact leaf, is simple, repeatable, and may be used at any plant age after leaf emergence. Incorporation (cpm/MUg protein) in 12 leaves per plant was compared among three inbred (Oh43, W23, M14) and three F1 hybrid (Oh43/M14, W23/M14, Oh43/W23) genotypes. The incorporation was 40% higher (hybrid versus inbred) in 9 of the 12 leaves studied. Samples from leaf 07 (7th leaf numbered from base of plant) for four inbreds (Oh43, M14, B73, Mol 7) and two pairs of reciprocal F1 hybrids (Oh43/M14, M14/Oh43; B73/Mo17, Mo17/B73) were labelled in situ using the leaf disc method. Each cultivar was sampled at three different ages in each of 1985, 1986, and 1987. High-resolution, two-dimensional isoelectric focusing sodium-dodecyl-sulfate polyacrylamide gel electrophoresis and fluorography were used to display the polypeptides synthesized in the samples. Multivariate methods - Principal Coordinate Analysis, Cluster Analysis, and Standard Deviation Distance - were used to analyze variation and to identify trends in the variation for year, genotype, and age sampled. Our analyses disclose a hierarchy to polypeptide synthesis variation in maize leaves: differences in polypeptide synthesis are greater for year-to-year comparisons than differences due to sample age, which in turn are greater than differences for inbred versus hybrid comparisons. PMID- 24221009 TI - Methods for predicting rates of inbreeding in selected populations. AB - In selected populations, families superior for the selected trait are likely to contribute more offspring to the next generation than inferior families and, as a consequence, the rate of inbreeding is likely to be higher in selected populations than in randomly mated populations of the same structure. Methods to predict rates of inbreeding in selected populations are discussed. The method of Burrows based on probabilities of coselection is reappraised in conjunction with the transition matrix method of Woolliams. The method of Latter based on variances and covariances of family size is also examined. These methods are one generation approaches in the sense that they only account for selective advantage over a single generation, from parents to offspring. Two-generation methods are developed that account for selective advantage over two generations, from grandparent to grandoffspring as well as from parent to offspring. Predictions are compared to results from simulation. The best one-generation method was found to underpredict rates of inbreeding by 10-25%, and the two-generation methods were found to underpredict rates of inbreeding by 9-18%. PMID- 24221010 TI - Inheritance of tolerance to rice tungro bacilliform virus (RTBV) in rice (Oryza sativa L.). AB - From a large number of rice varieties tested, no variety was identified as resistant to tungro bacilliform virus (RTBV). Only in Utri Merah was the RTBV multiplication restrictive, whereas other varieties such as Kataribhog and Pankhari 203 were identified as tolerant. These varieties were crossed with a susceptible variety. TN1, to study the inheritance of restrictive multiplication and tolerance to RTBV. After 3 weeks of inoculation with RTBV, F1; F2, and F3 progenies were assessed by enzyme-linked immunosorbent assay (ELISA). The RTBV concentration in all F1 populations was intermediate between parents. The frequency distribution of F2 seedlings with various levels of RTBV concentration indicated that the RTBV tolerance is controlled by multiple genes. The RTBV concentrations in F1 and F2 progenies from the Utri Merah x TN1 cross revealed that restrictive multiplication of RTBV in Utri Merah is a polygenic character. The continuous variation observed in F2 populations from crosses between tolerant varieties and Utri merah indicated no allelic relationships between tolerant and restrictive multiplication traits. PMID- 24221011 TI - Allozyme marker loci associated with favorable alleles for grain yield in maize. AB - The evaluation of germplasm to identify its potential as a source of new favorable alleles is a time-consuming phase of maize hybrid breeding programs. The objective of this paper was to study the relationship between allozyme diversity and quantitative estimators of the relative number of new favorable alleles for grain yield, present in donor lines but not present in the elite hybrid. Twenty-two maize inbred lines representing heterotic groups from the United States (US) and Yugoslavia (YU) were used as donors to estimate the presence of new favorable alleles for grain yield improvement for the hybrid B73 x Mo17. In a second experiment, a 15-line diallel was grown, and 13 single crosses differing in allozyme relatedness measure (ARM) and heterotic grouping were considered as targets to be improved by the remaining 13 lines. Minimally biased estimates of new favorable alleles for grain yield (MUG) and ARM values were made for all donor lines within each target hybrid. Donor lines were grouped in four allozyme-pedigree classes for each target hybrid to compare the effect of allozyme diversity with pedigree diversity. Pedigree dissimilarities had significant effects on MUG estimates. Dissimilar pedigree classes had higher MUG estimates than similar pedigree classes. Allozyme differences between donor inbred lines and target hybrids had inconsistent effects on MUG estimates. Significant differences in MUG estimates among allozyme classes were found for 31% of the target hybrids. Classes with similar allozymes had higher MUG estimates more frequently than classes with disimilar allozymes. Correlation coefficients between MUG estimates and ARM values were low and not significant for 12 of the 14 target hybrids. PMID- 24221012 TI - Multidisciplinary approach to genome analysis in the diploid species, Thinopyrum bessarabicum and Th. elongatum (Lophopyrum elongatum), of the Triticeae. AB - The J and E genome species of the Triticeae are invaluable sources of salt tolerance. The evidence concerning the phyletic relatedness of the J genome of diploid Thinopyrum bessarabicum and the E genome of diploid Th. elongatum (=Lophopyrum elongatum) is discussed. Low level of chromosome pairing between J and E at different ploidy levels, suppression of J-E pairing by the Ph1 pairing regulator that inhibits homoeologous pairing, complete sterility of the diploid hybrids (JE), karyotypic divergence of the two genomes, differences in total content and distribution of heterochromatin along their chromosomes, and marked differences in gliadin proteins, isozymes, 5S DNA, and rDNA indicate that J and E are distinct genomes. Well-defined biochemical markers have been identified in the two genomes and may be useful in plant breeding. The level of distinction between J and E is comparable to that among the universally accepted homoeologous genomes A, B, and D of wheat. Therefore, the J and E genomes are homoeologous and not homologous, although some workers continue to call them homologous. The previous workers' data on chromosome pairing in diploid hybrids and/ or karyotypic differences in the conventionally stained chromosomes do not provide sufficient evidence for the proposed merger of J and E genomes (and, hence, of the genera Thinopyrum and Lophopyrum) specifically and for establishing genome relationships generally. Extra precautions should be exercised before changing the designation of an established genome and before merging two genera. A uniform, standardized system of genomic nomenclature for the entire Triticeae is proposed, which should benefit cytogeneticists, plant breeders, taxonomists, and evolutionists. PMID- 24221013 TI - Intergeneric hybridization between Diplotaxis siifolia, a wild species and crop brassicas. AB - Attempts were made to obtain intergeneric hybrids between Diplotaxis siifolia, a wild species, and cultivars of Brassica (B. campestris, B. juncea, and B. napus). The crosses showed unilateral incompatibility. When the wild species was used as female parent, pollen germination and pollen tube growth were normal, but hybrid seeds aborted due to post-fertilization barriers. Reciprocal crosses (cultivars as female parent) showed strong pre-fertilization barriers; although pollen grains showed germination, pollen tubes failed to enter the stigma. Hybrids were realized in two of the crosses, D. siifolia x B. juncea and D. siifolia x B. napus, through ovary culture. The hybrids were multiplied in vitro by multiplication of axillary shoots, or somatic embryogenesis. Detailed studies were carried out on the hybrid D. siifolia x B. juncea. F1 hybrids had shrivelled anthers and were pollen sterile. Amphiploids of this hybrid showed 60% pollen fertility and produced seeds upon self-pollination as well as backcross pollination with the pollen of B. juncea. PMID- 24221014 TI - Durable resistance to two leaf blights in two maize inbred lines. AB - It has been determined that the occurrence of 'durable resistance' as defined by Johnson and Kranz operates in maize inbred lines CM104 and CM105 against the leaf blight pathogens Setosphaeria turcica (= Exserohilum turcicum) and Drechslera maydis (=Cochliobolus heterostrophus), by analyzing data for 16 and 14 years, respectively. Essentially the methodology estimated the longevity of cultivar resistance by determining whether the regression coefficient of linear regression with years of testing and mean disease intensity is zero or not significantly different from zero. The values for both Turcicum Leaf Blight and Maydis Leaf Blight were not significantly different from zero. The resistant inbred lines have been used in hybrid combinations and have the potential to transmit this resistance to progenies in hybrid combinations that are governed by additive gene action. PMID- 24221015 TI - Fertile somatic hybrids of Solanum species: RFLP analysis of a hybrid and its sexual progeny from crosses with potato. AB - Restriction fragment length polymorphism (RFLP) markers were used to distinguish the chromosomes of Solanum brevidens from those of potato (S. tuberosum) in a fertile somatic hybrid. The hybrid had markers that account for all 24 chromosome arms from each parent, indicating that the hybrid contained at least one copy of each chromosome from each parent. The markers were then used to follow segregation of chromosomes in sexual progeny that resulted from a cross of the somatic hybrid with the potato cultivar 'Katahdin'. Approximately 10% of the sexual progeny lacked one or more of the markers specific to S. brevidens. No one chromosome or marker appeared to be lost preferentially. This infrequent absence of a chromosome marker derived from the wild parent could be explained by intergenomic pairing and recombination. The loss of a marker band for chromosome 8, coupled with the retention of two flanking markers, suggested that a small region of DNA was deleted during regeneration of the somatic hybrid. These results show the value of RFLP analysis when applied to somatic hybrids and their progeny. Clearly, RFLPs will be useful for following the DNA from wild species during its introgression into potato cultivars. PMID- 24221016 TI - Quantitative analysis of correlations among flower traits in Gerbera hybrida Compositae : 1. Genetic and environmental correlations. AB - Phenotypic (r p ), genetic (r g ), and environmental, (r e ) correlations were estimated for 38 flower traits in the Davis population of gerbera (Gerbera hybrida, Compositae). Fifty-two percent of r p and 38% of r g were statistically significant at P < 0.05. Significant negative r p were infrequent, but significant negative r g occurred in 10% of cases. There was a negative correlation between estimates of r g and r e , resulting in cases where r g was significant, but r p was not. Individual traits varied in their tendency to correlate phenotypically or genetically, and positively or negatively, with other traits. Traits within the same morphological category, such as disk florets or transitional florets, were more highly intercorrelated than were traits from different categories. PMID- 24221017 TI - Quantitative analysis of correlations among flower traits in Gerbera hybrida, Compositae : 2. Direct and mean correlated response to selection. AB - A Mean Correlation Response (MCR) model was developed to estimate the relative effectiveness of direct selection when other traits also respond to the selection. A measure of the relative effects of mean correlated response and direct response (R) and a measure of the relative efficiency of direct selection (IE) were applied to a genetic correlation matrix of 38 traits. These were measurements of inflorescence, receptacle and involucre, scape, disk florets, ray florets, and trans florets in the Davis population of Gerbera hybrida, Compositae. Generally, traits with high heritability had high direct and mean correlated response; these were often traits measuring disk and trans florets. Traits with low heritability had low direct and mean correlated response; these were often traits measuring the inflorescence. Traits of the inflorescence had the lowest efficiency of direct to mean correlated response. PMID- 24221018 TI - Recurrent selection alternating with haploid steps - a rapid breeding procedure for combining agronomic traits in inbreeders. AB - Doubled haploid lines are increasingly used in practical breeding programs. Depending on the nature of the starting material as well as on the breeding aims, one or more haploid steps are recommended, and F1 hybrids or selfed progenies in later generations serve as starting material for the haploidization. It is demonstrated that one haploid step followed by selection in the greenhouse and in the field during the first androgenetic (A1) and two subsequent selfed generations (A2; A3) is the most efficient procedure, if characters from related varieties are to be combined. For breeding programs that include wild types or unrelated genotypes, recurrent selection alternating with several haploid steps is the most efficient. A prerequisite for successful application of this combination of repeated haploidization and selection steps alternating with backcrosses is an effective selection system. The different approaches are demonstrated on a winter barley breeding program, with the central aim of combining the qualitatively inherited character resistance to barley yellow mosaic virus with quantitatively inherited complexes, particularly yield. PMID- 24221019 TI - Heterosis in crosses between geographically separated populations of Drosophila melanogaster. AB - An experiment was performed to test the hypothesis that the genetic distance between populations estimated from enzyme loci could be used to predict the amount of heterosis that would occur in crosses between these populations. A partial diallel cross using 11 populations of Drosophila melanogaster from the AustralianPacific region and from England was carried out. Heterosis for larval viability, fecundity, cold shock mortality, and an index of these three traits was recorded. When two populations originating from the same location were crossed, no heterosis occurred, but otherwise heterosis was significant for all traits. For larval viability, a similar low level of heterosis occurred in all crosses. For cold shock mortality, the level of heterosis varied widely and fecundity showed a pattern intermediate between these two. The geographic distance between the sites from which populations originated was not correlated with the amount of heterosis in their crosses. There was a tendency for populations from ecologically different environments to show heterosis in crosses. Genetic distance based on ten enzyme loci was correlated with heterosis for cold shock mortality and the combined trait index. These results can be explained by the hypothesis that genes affecting larval viability are subject to strong, uniform selection in all populations, which limits the extent to which gene frequencies can drift apart. However, genes affecting cold shock mortality and the enzyme loci are subject to different selection pressures in different environments. This divergent selection combined with genetic drift causes divergence in gene frequency and heterosis. PMID- 24221020 TI - The spectrum of facial fractures in motor vehicle accidents: an MDCT study of 374 patients. AB - Road traffic accidents are a major health problem worldwide resulting frequently in maxillofacial injuries. The purpose of the study was to assess the incidence and spectrum of facial fractures in patients involved in a motor vehicle accident (MVA). Using picture archiving and communication system, all requests for suspected facial trauma were retrieved during a 62-month period; 374 met the inclusion criteria. Two researchers interpreted the multidetector computed tomography images by consensus. The motor vehicles involved were divided into two groups: those involving a passenger car or a larger vehicle and those involving a motorized two-wheeler. Furthermore, the motor vehicle accidents were divided into collisions and run-off-road accidents. Of the 374 patients (aged 15-80, mean 34), 271 (72 %) were male and 103 (28 %) female. Of all patients, 262 (70 %) had a facial or skull base fracture; of these, multiple separate fractures were present in 56 %. Nasal fractures were the most common fractures followed by orbital, skull base, and maxillary fractures. Frontal bone, LeFort, and zygomatic arch fractures were always accompanied by other fractures. Fractures were more frequent in the group of collisions compared with run-off-road accidents. In the two-wheeled group, only 15 % did not have facial or skull base fractures. Fractures often occur in multitudes as 39 % of all patients have multiple facial or skull bone fractures, and thus, emergency radiologists should be familiar with the complexity of the injuries. Negative clear sinus sign and low-energy sentinel injuries should be trusted as indications of undetected injuries in MVA victims. PMID- 24221022 TI - Multi-element geochemical analysis of snow samples: Use of discriminant analysis in interpreting the results. AB - This paper records the concentrations of major and trace elements determined from snow samples collected during a comprehensive survey undertaken in the Scottish Highlands during the winter and spring period of 1987. The configuration of calculated back-trajectories allowed the samples to be categorized into one of five geographical sectors. Discriminant analysis was used to check the validity of these calculations, to isolate potentially deviant samples, and to predict the possible source of one sample whose back-trajectory could not be computed with confidence. Limitations of the statistical method are discussed, but we conclude that the technique justifies more use by environmental scientists involved in the evaluation of data. PMID- 24221021 TI - Two tobacco AP1-like gene promoters drive highly specific, tightly regulated and unique expression patterns during floral transition, initiation and development. AB - The genetic engineering of agronomic traits requires an array of highly specific and tightly regulated promoters that drive expression in floral tissues. In this study, we isolated and characterized two tobacco APETALA1-like (AP1-like) promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using the GUS reporter system, along with tissue-specific ablation analyses. Our results demonstrated that the two promoters are active in floral inflorescences but not in vegetative apical meristems or other vegetative tissues, as reflected by strong GUS staining and DT-A-mediated ablation of apical shoot tips during reproductive but not vegetative growth. We also showed that the NtAP1Lb1 promoter was more active than NtAP1La in inflorescences, as the former yielded higher frequencies and greater phenotypic evidence of tissue ablation compared to the latter. We further revealed that both promoters were uniformly expressed in the meristems of stage 1 and 2 floral buds, but were differentially expressed in floral organs later during development. While NtAP1La was found to be active in stage 4-5 carpels, later becoming confined to ovary tissue from stage 9 onwards, NtAP1Lb1 activity was apparent in all floral organs from stages 3 to 7, becoming completely absent in all floral organs from stage 11 onward. Therefore, it seems that the two tobacco promoters have acquired similar but distinct inflorescence-, floral meristem- and floral organ-specific and development-dependent regulatory features without any leaky activity in vegetative tissues. These features are novel and have rarely been observed in other flower-specific promoters characterized to date. The potential application of these promoters for engineering sterility, increasing biomass production and modifying flower architecture, as well as their putative use in flower-specific transgene excision, will be discussed. PMID- 24221023 TI - Seasonal ecology of hydrocarbon-utilizing microbes in the surface Waters of a river. AB - Seasonal changes in the microbial communities of the New Calabar Riverwater have been investigated. Analyses of the BOD, pH, salinity, oil and grease levels of effluents of industries sited along the river were also conducted. High hydrocarbon-utilizing microbial populations were found. The percentage of hydrocarbon-utilizing heterotrophic bacteria ranged between 0-98% and 0-68% in the rainy and dry months, respectively. Counts of hydrocarbon-utilizing actinomycetes in the rainy months ranged between 0-95% and 2-55% in the dry months. The hydrocarbon-utilizing yeast population ranged between 1-95% and 2-85% for the rainy and dry months, respectively. Rainy month values for hydrocarbon utilizing mould population ranged from 0-17% while dry month values ranged from 0 47%. The hydrocarbon-utilizing cyanobacterial population ranged between 0-95% and 0-33% in the rainy and dry months, respectively. Our results suggest that the heterotrophic bacterial and cyanobacterial populations are higher in the rainy months than in the dry months. However, the hydrocarbon-utilizing yeast, mould and actinomycete populations did not show seasonal variation. PMID- 24221024 TI - Importance of eating habits and sample size in the estimation of environmental mercury contamination using biological indicators. AB - The importance of eating habits and the number of fish sampled in the estimation of mercury environmental contamination through biological indicators was studied. The species used were one with piscivorous habits (Anguilla anguilla) and another with omnivorous habits (Ciprinus carpio). From one original sample for each species, randomized samples were generated using the subroutine GGSRS from the mathematics library IMSL, and later the statistical significance of Pearson's correlation coefficient for the relationship between fish weight and mercury concentrations in muscle was obtained for each random sample. The results show that the use of omnivorous species such as Ciprinus carpio as a biological indicator of contamination enables us to carry out estimations with a greater degree of confidence than when piscivorous species such as Anguilla anguilla are used. PMID- 24221025 TI - Statistical trends in ground-water monitoring data at a landfill Superfund site: A case study. AB - This paper describes the use of statistical regression models to characterize temporal trends in groundwater monitoring data collected between 1980 and 1990 on 15 wells and 13 parameters (195 cases in all) at the KL Avenue landfill site in Kalamazoo County, Michigan. This site was used as a municipal landfill prior to 1980, then was placed on the Superfund site list in 1982 after ground-water contamination was found.Six temporal regression trend models were defined using linear and quadratic regression models. These trends were used to classify each of the 195 cases as: improving, deteriorating, or stable over the 1980-1990 time period. Using these classifications it was determined that there were more than twice as many improving cases as deteriorating conditions at the KL site during this time period. These models provide a method for visualizing and interpreting trends in ground-water quality at individual well locations within the contaminant plume and for assessing the chemical trend behavior of the overall plume. The improving, deteriorating, and stable trend categories were developed for two purposes. The first purpose is to facilitate comprehension of information contained in large amounts of water quality data. The second is to assist communication among the many different groups of people who recommend actions, including remediation responsibilities at Superfund sites, like the KL site.A normal probability model was used in the trend classifications. This model contained provisions to accommodate nondetect data and other 'abnormal' laboratory determinations which can influence the trend selection process. The robustness of this classification procedure was examined using a lognormal probability model. The overall conclusions about the KL site using the lognormal model were similar to those obtained using the normal model. However, some individual trend indications were different using the lognormal model. The Shapiro-Wilk test was used to check the adequacy of both the normal and lognormal models. The lognormal model was found to be a somewhat more adequate model for fitting the KL site data, but was not found to be superior to the normal model for each case.The normal and lognormal models were both found to be suitable for determining overall trend conditions at this site. Both models are recommended for these purposes assuming an understanding of the statistical constraints and hydrochemical context. However, it is recommended that the search for more adequate trend models continues. PMID- 24221026 TI - Biological monitoring of particulate pollutants during exploration work at a niobium mineralization in Greenland. AB - The purpose of this investigation was to monitor airborne dipersion of particulates in connection with exploration activities at a niobium mineralization in the Sarfartoq area, SW Greenland, during the summer of 1989, and to provide a basis for monitoring strategies in later phases of the development of the mining site. During three periods moss bags were exposed at 9 stations close to the outcrop and at 3 background stations, and indigenous lichens and mosses were sampled before and after the exploration work.Analyses of element concentrations showed that the natural enrichment of elements in the indigenous vegetation is restricted to areas immediately at or on the outcrop. The elements found in elevated concentrations were Nb, La, Ce, Th and U.The moss bags and the indigenous monitor organisms showed rises in concentrations of the elements Nb, Ce, Cd, Pb and Zn after the exploration activities during the summer. This shows that some dispersion of dust has occurred in the area. PMID- 24221027 TI - Phylogeography-based delimitation of subspecies boundaries in the common pheasant (Phasianus colchicus). AB - To test the validity of subspecies status within the common pheasant (Phasianus colchicus), we used genetic data to assess differences among five subspecies distributed across the Loess Plateau in central China. Samples were collected from 191 individuals representing subspecies P. c. strauchi, P. c. satscheuensis, P. c. kiangsuensis, P. c. suehschanensis, and P. c. edzinensis. Analysis of mitochondrial genetic variation suggested that there were no phylogenetically distinct subspecies clades, and we could not exclude that hybridization has occurred among subspecies. A potential explanation of the observed pattern is that an increase in common pheasant rearing farms may have led to enforcement of hybridization between different subspecies. Consistent with phenotypic data, our analysis suggests that a previously identified common pheasant subspecies (P. c. strauchi) represents an intermediate form between the subspecies P. c. satscheuensis and P. c. suehschanensis. PMID- 24221028 TI - Ascorbate-2-sulfate as a dietary vitamin C source for atlantic salmon (Salmo salar): 1. Growth, bioactivity, haematology and humoral immune response. AB - The present experiment shows that ascorbate-2-sulfate (AS) is not equivalent to ascorbic acid (AA) as a dietary vitamin C source for Atlantic salmon (Salmo salar). Within reasonable feed supplemental levels AS does not provide the tissues with adequate supplies of vitamin C to secure optimal physiological functions as demonstrated by biochemical and haematological analyses.AS could not be detected in the liver of fish fed either AA or AS, nor in vitamin C - deprived salmon, suggesting that AS is not the natural storage form of vitamin C in this species.There were no significant differences in antibody production against a soluble artificial antigen (NIP11-LPH) in fish fed 500 and 5000 mg AA/Kg dry diet or equivalent amounts of AS during a period of six weeks at a water temperature of 7.2 degrees C. PMID- 24221029 TI - Ascorbate-2-sulfate as a dietary vitamin C source for Atlantic salmon (Salmo salar): 2. Effects of dietary levels and immunization on the metabolism of trace elements. AB - Atlantic salmon fingerlings were fed a vitamin C deficient diet for four months. The fish were then provided a dry, practical fishmeal based diet supplemented with 0, 500 or 5000 mg vitamin C/kg as L-ascorbic acid or equivalent amounts of ascorbate-2-sulfate. After six weeks on these diets ten fish in each group were injected with a soluble antigen (NIP11-LPH). Six weeks thereafter blood, liver, kidney, spleen and vertebrae were examined for trace elements. The livers were also analysed for metallothionein.The vitamin C deficient fish were anemic despite the significantly elevated iron concentrations in the liver. Vitamin C had no positive effect in lowering tissue levels of cadmium. The highest level of dietary vitamin C given as ascorbic acid reduced the liver selenium concentrations. In response to antigen injection, the fish in all groups showed increased levels of hepatic metallothionein, copper, zinc and cadmium, while hepatic selenium and iron levels were less affected. The elemental composition in other organs was affected by the antigen injection to a minor extent. PMID- 24221030 TI - Isolation, properties and induction of plaice liver cytosolic glutathione-S transferases. AB - Three cytosolic glutathione S-transferases [E.C. 2.5.1.18] were identified in liver of a marine flatfish, the plaice (Pleuronectes platessa) and the two major isoforms were purified to homogeneity. There was no evidence for the presence of basic transferases. The plaice GST's exhibited comparable hematin binding to rat ligandin, however, bilirubin was only bound weakly and the enzymes did not display the inhibition characteristics of ligandin. They were extremely sensitive to inhibition by organotin compounds.Plaice transferase A was a homodimer of Mr 27 kDa subunits; it displayed strongest activity with CDNB and some activity with DCNB as substrates. Specific antibodies to it did not show any relationship with other plaice GST's or rat GST subunits 1,2,3,4,7,8 or 10. Plaice transferase B was a homodimer of Mr 25 kDa subunits, it displayed similar activities with CDNB and DCNB as substrates to transferase A and a low activity with ethacrynic acid or p-nitrobenzylchloride. It was immunologically related to the rat alpha class transferase subunits 1,2 and 8. A minor form, transferase AM, which was not separated from transferase A, appeared to be a heterodimer of Mr 25.5 and 27 kDa subunits. It displayed a greater activity with DCNB than the other plaice GST's and some activity with bromosulphalein indicative of a possible relationship with the Mu class transferases. PMID- 24221031 TI - An increase in the concentration of hepatic iron during the metamorphosis of the lamprey Geotria australis is accompanied by increased superoxide dismutase activity. AB - The concentration of total non-haem iron and its ferritin iron component, and the activity of the enzyme superoxide dismutase (SOD), were measured in the livers of ammocoetes, metamorphosing animals (stages 1-7) and recently metamorphosed downstream migrants of the lamprey Geotria australis. Total non-haem iron in the liver rose significantly from 0.15-0.55 MUg.mg wet weight(-1) in ammocoetes and metamorphosing stages 1-3 to 2.2-2.9 MUg.mg(-1) in stages 5-7 and to 8.8 MUg.mg( 1) in downstream migrants. The comparable values for ferritin iron were 0.06 0.26, 1.4-2.0, and 5.3 MUg.mg(-1). Superoxide dismutase activity fell sharply from 0.39 MUg.mg(-1) in large ammocoetes to between 0.07 MUg.mg(-1) in stage 1 and 0.15 MUg.mg(-1) in stage 6, before rising significantly to 0.26 MUg.mg(-1) in stage 7 and 0.35 MUg.mg(-1) in downstream migrants. The sharp fall in SOD activity at the beginning of metamorphosis is assumed to be related to the marked decline in plasma iron which occurs at the onset of this non-trophic phase in the life cycle. It is proposed that the subsequent increase in SOD activity in the liver of G. australis with increasing iron represents a mechanism aimed at reducing the potentially toxic effects of iron accumulation. This view is consistent with the significant and positive correlation found between both total non-haem and ferritin iron and SOD activity in the liver of non-trophic animals. PMID- 24221032 TI - Interrelationships between red cell nucleoside triphosphate content, and blood pH, O2-tension and haemoglobin concentration in the carp, Cyprinus carpio. AB - As a starting point for investigations of possible control factors for the nucleoside triphosphate content in carp red cells, we utilized the natural variability in blood physico-chemical parameters to test for interrelationships. By application of two-variable regression analysis, the red cell NTP content was found to be significantly correlated with arterial PO 2 and pH as well as with the blood haemoglobin (Hb) concentration. These correlations show a rise in red cell NTP content with falling pH as well as with falling Hb concentration, whereas a decrease in PO 2 was associated with a decrease in the content of NTP, particularly at low PO 2 values. Evaluation based on multiple regression analysis suggested that only PO 2 and pH significantly affected the red cell NTP content, and that the influence of changes in Hb concentration could be accounted for by naturally occurring simultaneous changes in PO 2 and pH. The multifactorial control of red cell nucleoside triphosphates is discussed in relation to the role of still unknown factors. PMID- 24221033 TI - Anatomic and metabolic responses to thermal acclimation in the ninespine stickleback, Pungitius pungitius. AB - Male ninespine sticklebacks, Pungitius pungitius, acclimated to 3 degrees C have higher activities of mitochondrial enzymes in their axial muscles than males acclimated to 20 degrees C. Phosphofructokinase and pyruvate kinase activities tended to be higher in cold than warm acclimated males. For females, warm acclimation tended to decrease only mitochondrial enzyme activities. As thermal acclimation did not change the physical condition and most anatomic parameters of the sticklebacks, the enzymatic changes do not seem due to mobilization of somatic reserves. Field acclimatization to warm temperatures led to a marked decrease in physical condition in both males and females. This decrease in physical condition could largely be attributed to atrophy of the carcass mass. Spring males had higher activities of phosphofructokinase, citrate synthase and cytochrome oxidase in the axial muscle than summer males. Again, females showed a less marked response. These data suggest that environmental temperature is a major determinant of muscle aerobic capacity, at least for male ninespine sticklebacks. Thus, these northern temperate zone fish retain the capacity for thermal compensation, much like their temperate zone counterparts. PMID- 24221034 TI - Mitochondrial NAD(P)-dependent malic enzyme from herring testicular tissue: Purification, kinetic behaviour and regulatory properties. AB - Mitochondrial NAD(P)-dependent malic enzyme [EC 1.1.1.39, L-malate: NAD(+) oxidoreductase (decarboxylating)] was purified from herring testicular tissue to a specific activity of 26.4 MUmol NADH/min/mg protein. Herring testicular tissue is one of the most abundant sources of this enzyme. The purification procedure involved differential centrifugation of mitochondria and then chromatography on DEAE-Sephacel, Red Agarose and Sephacryl S-300. This enzyme catalyzes the oxidative decarboxylation of malate in the presence of Mn(2+) and either NAD or NADP. Under Vmax conditions the ratios for the rate of NAD/NADP reduction was 1.8. A study of the reductive carboxulation reaction indicated that this enzyme reaction is reversible; at pH 7.0 the reverse reaction exhibited 22% of the activity of forward reaction. Some kinetic characteristics of the enzyme were determined. ATP was found to be a competitive inhibitor with respect to malate. Fumarate reversed ATP inhibition. Regulation of NAD(P)-dependent malic enzyme from herring testicular tissue mitochondria could respond to changing levels of mitochondrial ATP and fumarate in vivo. PMID- 24221035 TI - Proteins of seminal fluid and spermatozoa in the trout (Oncorhynchus mykiss): Partial characterization and variations. AB - The protein composition of seminal fluid, blood serum, sperm plasma membrane and flagellum of rainbow trout were analysed by SDS-polyacrylamide gel electrophoresis. Immunological identity between proteins of the 2 fluids and sperm components was studied using crossed immunoelectrophoresis, rocket immunoelectrophoresis and immunoblotting. Results indicate that many seminal proteins are antigenically-related to serum proteins, proteins of sperm origin are present in seminal fluid in varying amounts, depending on the animals and sampling time, and several serum-like seminal proteins are bound to spermatozoa.Lipoproteins were isolated from seminal fluid (mean level: 33 MUg/ml) and characterized. They were identified as being HDL-like lipoproteins. A possible physiological role is proposed for these seminal lipoproteins. PMID- 24221036 TI - Short communication: Induced ovulation of sablefish (Anoplopoma fimbria) following oral administration of des Gly(10)-(D-Ala (6))LH-RH ethylamide. PMID- 24221038 TI - Salinity and temperature effects on whole-animal thyroid hormone levels in larval and juvenile striped bass, Morone saxatilis. AB - Whole-animal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels were measured in larval and juvenile striped bass, Morone saxatilis, reared for 10 days at one of three levels of salinity (equivalent to fresh water (FW), one-third seawater (1/3 SW), and seawater (SW) and two temperatures (15 degrees C and 20 degrees C). The striped bass were pre-metamorphic larvae, metamorphic larvae or juveniles. The short-term effects of seawater on plasma T4 levels of juvenile striped bass were also measured. Higher salinities increased T4 levels in premetamorphic larvae. In metamorphic larvae, SW and 1/3 SW increased T4 levels and SW increased T3 levels at 20 degrees C. This response was eliminated in those at 15 degrees C. Whole-animal thyroid hormone content was unaffected by salinity or temperature in juvenile striped bass, although significant fluctuations in plasma T4 levels occurred in those transferred to 1/3 SW and SW. The thyroid axis of striped bass responds to salinity and temperature as early as in the pre-metamorphic stage. Thyroid hormones may mediate the beneficial effects of salinity on larval striped bass growth and survival. PMID- 24221037 TI - Distribution of 5-hydroxytryptamine and related compounds in various brain regions of rainbow trout (Oncorhynchus mykiss). AB - The levels of tryptophan (Try), 5-hydroxytryptamine (serotonin, 5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) were determined in the brain regions of rainbow trout (Oncorhynchus mykiss) by high performance liquid chromatography with electrochemical detection (HPLC-EC). Brain tryptophan concentrations varied from 3.972 +/- 357 ng/g cerebellum) to 8.841 +/- 772 ng/g (hypothalamus). The 5-HT concentrations varied from 69 +/- 7 ng/g (optic tectum) to 573 +/- 34 ng/g (hypothalamus). The concentrations of 5-HIAA varied from 29 +/- 3 ng/g (medulla oblongata) to 68 +/- 7 ng/g (hypothalamus). Total and free serum tryptophan levels were also determined; in adult rainbow trout 92% of the serum tryptophan was observed to be free i.e., not protein-bound. PMID- 24221039 TI - Thyroid hormones in eggs of various freshwater, marine and diadromous teleosts and their changes during egg development. AB - Thyroid hormone concentrations in unfertilized eggs of 26 species of various freshwater, marine and diadromous teleosts were examined, together with changes in their concentrations during egg development in some species. Significant quantities of both thyroxine (T4) and triiodothyronine (T3) were found in eggs of all species examined. Mean T4 and T3 concentrations in eggs varied from 0.04 (marbled sole) to 15.00 ng/g (chum salmon), and from 0.07 (goldfish) to 9.95 ng/g (Pacific herring), respectively. T4 concentrations were significantly greater than T3 concentrations in eggs of most freshwater fishes, whereas T3 concentrations were greater in seawater fishes. During the course of development, thyroid hormones in eggs decreased markedly before hatching. These findings suggest that thyroid hormones are consistently present in teleost eggs, and thus may play an important role in the egg development. PMID- 24221040 TI - Effects of calcium channel blockers on pharmacologically induced contractions of rainbow trout (Oncorhynchus mykiss) intestine. AB - Calcium depletion/replacement studies were carried out to examine the role of calcium in contraction of trout intestinal smoot muscle in vitro. Three chemically distinct calcium channel blockers were used to determine whether voltage operated calcium channels (VOCs) were involved in calcium entry with either agonist or depolarization-induced contractions. Contractions induced by depolarizing intestinal smooth muscle with potassium were totally dependent on extracellular calcium, whereas receptor-mediated responses to 5-hydroxytryptamine (5-HT) and carbachol also relied on calcium derived from intracellular stores. The calcium channel blockers, verapamil, nitrendipine, and diltiazem, all shifted the calcium-response curve for potassium to the right, supporting the existence of VOCs in trout intestinal smooth muscle. The calcium-response curve for 5-HT was also shifted to the right, suggesting that 5-HT can induce calcium uptake into the smooth muscle via VOCs, in addition to mobilizing intracellular calcium. Verapamil also appeared to block 5-HT receptors directly. Carbachol-induced contractions were only reduced by diltiazem at low concentrations of calcium (0.1 1 mM), suggesting that diltiazem has some other mechanisms of action than the other calcium channel blockers. Activation of muscarinic receptors may induce calcium entry through channels other than the VOCs, in addition to mobilizing intracellular calcium. PMID- 24221041 TI - Purification and physicochemical properties of deoxyribonuclease from pyloric caeca of Atlantic cod (Gadus morhuaL.). AB - A deoxyribonuclease (DNase) of pancreatic origin has been purified from extracts of the pyloric caeca from Atlantic cod (Gadus morhua L.). The crude extract was prepared by mincing frozen caeca tissue in equal volumes of buffer. The enzyme was isolated from the supernatant after streptomycin sulfate precipitation and centrifugation. The purification scheme further included chromatography on Q Sepharose Fast Flow and hydroxyapatite columns. Affinity adsorption chromatography of the hydroxyapatite fraction on 8-(6-aminohexyl)-amino-5'-AMP Sepharose, revealed an apparently homogeneous protein with molecular weight of 35,000 Da as judged by NaDodSO4-PAGE. In sum a 644-fold enzymatic enrichment and 3.5% total enzyme recovery was achieved. The cod enzyme resembles DNase I-type enzymes with an alkaline pH activity optimum and shows dependency for Mg(2+). The pI of the enzyme is 6.5 as determined by isoelectric focusing and DNase zymography. Our findings suggest that the nuclease is a member of the cod's digestive enzymes secreted from the connective tissue surrounding the caeca. PMID- 24221042 TI - Optical properties of the pineal window of Atlantic salmon (Salmo salar L.). AB - The spectral composition and intensity of light penetrating different parts of fresh preparations of the upper part of the skull of Atlantic salmon (Salmo salar) (fork length 25-30 cm) was investigated. All measurements were made in an aqueous medium, by moving the tip of an optical fibre in a three dimensional lattice below preparations that were illuminated by a parallel light source from above. The intensity of the transmitted light showed a well-defined maximum just below the pineal groove. Light that penetrated the skull from a source vertically above was refracted to produce a focusing point in the approximate position of the pineal body. Light projected from angles of 45 degrees relative to the vertical position was only slightly (25%) attenuated, thus indicating a wide acceptance angle.There was an almost uniform transmission of light (of 3%) between 500 and 700 nm. The transmittance of UV light (350 nm) was about 10% of that of green light. These differences are small when compared with the intensity range reported for the pineal light receptors. The transmission properties are discussed in relation to the known diurnal changes in the spectral composition of natural light. PMID- 24221044 TI - Contents, vol. 8, nos. 1-6, 1990. PMID- 24221045 TI - Transfer and stability of drug resistance plasmids inEscherichia coli K12. AB - Mating experiments between pairs of strains ofEscherichia coli containing either the compatible plasmids TP120 (Inc N) and R1 (Inc FII) or the incompatible plasmids TP125 (Inc B) and TP113 (Inc B) were undertaken in mixed continuous-flow cultures and in dialysis sacs suspended in pond water. Plasmid transfer was readily demonstrated between strains carrying compatible plasmids TP120 and R1 in both continuous-flow culture and pond water. In mixed cultures of strains carrying plasmids TP125 and TP113, transfer was only observed in continuous-flow culture systems. Strains ofE. coli containing aggregates of plasmids TP120 and R1 were shown to be stable over 5 months continuous cultivation under carbon limited conditions at a growth rate of 0.1 hours(-1) in the presence of drugs which select for the maintenance of both plasmids. In the strains containing plasmid aggregates, a gene dosage effect was observed with respect to the levels of resistance to drugs whose resistance was encoded by both plasmids. Chemostat experiments showed that no cointegrate plasmids were found from the strains ofE. coli initially containing both plasmid TP120 and plasmid R1. PMID- 24221046 TI - Characteristics of some fermentative bacteria from a thermophilic methane producing fermenter. AB - Anaerobic bacteria from a 55?C methane-producing beef waste fermenter were enumerated, isolated, and characterized. Direct microscopic bacterial counts were 5.2-6.8*10(10) per g fermenter effluent. Using a nonselective roll-tube medium which contained 40% fermenter effluent, 8.5-14.1% of the microscopic count was culturable. Deletion of fermenter effluent significantly reduced the viable count. Sixty-four randomly picked strains were characterized. All were pleomorphic, gram-negative, anaerobic rods, many of which were difficult to grow in liquid media. The strains were divided into 5 major groups based on glucose fermentation, hydrogen sulfide production, starch hydrolysis, fermentation products, and morphology. Glucose was fermented by 75% of the isolates, 76% utilized starch, 25% produced hydrogen sulfide, 76% produced hydrogen, 37% produced indole, 21% hydrolyzed gelatin, and 13% were sporeformers. Ethanol, lactate, formate, acetate, and hydrogen were common fermentation products. Twenty four representative strains had 1-12 flagella. Growth was observed between 35 and 73?C. These studies indicate that species diversity among the isolated organisms was low. PMID- 24221047 TI - Measurement of nitrification rates in lake sediments: Comparison of the nitrification inhibitors nitrapyrin and allylthiourea. AB - A method for measuring rates of nitrification in intact marine sediment cores has been modified and adapted for use in freshwater sediments. The technique involves subsampling a sediment core into minicores. Half of these cores are treated with an inhibitor of chemolithotrophic nitrification and, after incubation, differences in ammonia and nitrate concentration between inhibited and uninhibited systems are calculated. The within-treatment variability of ammonia and nitrate concentrations could be reduced by storing the cores overnight prior to subsampling. Estimates of the nitrification rate using the difference in ammonia concentrations between the inhibited and uninhibited mini-cores were always greater than the rate estimate using the difference in nitrate concentrations. Comparison between the results using the nitrification inhibitors allylthiourea (ATU) and nitrapyrin (N-Serve) indicated that the former appeared to give larger values for the nitrification rate than did the latter. Differences in the efficiency of these inhibitors in the control of nitrification under the conditions used partly explain these results. Data are also presented on the effect of N-Serve and ATU on some other nitrogen transformations affecting ammonia and nitrate concentrations. PMID- 24221048 TI - The contribution of nitrification in the water column and profundal sediments to the total oxygen deficit of the hypolimnion of a mesotrophic lake (Grasmere, English Lake District). AB - Estimates ofin situ nitrifying activity have been made in the hypolimnetic water column and surface 1.0 cm of profundal sediments at 2 sites in Grasmere, a mesotrophic lake in the English Lake District. Increases of nitrate concentrations were used to estimate nitrification in the water column whereas a mini-core technique, involving the use of a nitrification inhibitor (allylthiourea), was used to estimate the rate in surface sediments. The pattern of oxygen depletion in the water column was used to estimate the maximum depth to which sediments affect the overlying water. Nitrification in the sediment and in the water column made approximately equal contributions to the total areal oxygen deficit and, as a whole, nitrification accounted for 15-20% of the total oxygen depletion. There was no significant difference in oxygen depletion due to nitrification between the 2 sites. Attempts were made, using the nitrification potential technique, to determine the depth distribution of nitrifying activity in the surface 1.0 cm of sediment. PMID- 24221049 TI - Survival of ciliate protozoa under starvation conditions and at low bacterial levels. AB - Under starvation conditions, 50% survivorship times displayed no significant relationship with cell size in 2 ciliate species in this study and 5 protozoan species from the literature. Differences in survival ability were attributed to differences in weight-specific respiratory rate and relative motility among these 7 species. At low bacterial levels, 4 ciliate species in this study displayed significant differences in survivorship. High survivorship ofEuplotes patella relative to that ofParamecium caudatum andParaurostyla sp. at low ciliate densities was attributed to the lower individual energy requirements of this smaller species. High survivorship ofStentor coeruleus was interpreted as an effect of its large quantity of reserves and low respiratory rate. The survivorship ofE. patella was reduced at a higher population density. Four ciliate species survived longer at 15?C than at 22?C. Q10 values based on 50% survivorship times at these 2 temperatures were much lower than Q10 values based on respiratory rates and growth rates of well-fed ciliates over a similar temperature range. PMID- 24221050 TI - Competition of two suspension-feeding protozoan populations for a growing bacterial population in continuous culture. AB - Mathematical studies for ecosystems involving 2 predators competing for a growing prey population have shown that the 2 competitors can coexist in a state of sustained oscillations for a range of values of the system parameters. For the case of 1 suspension-feeding protozoan population, recent experimental observations suggest that the predator-prey interaction is complicated by the ability of the bacteria to grow on products produced by the lysis of protozoan cells. This situation is studied here for the case where 2 suspension-feeding protozoan populations compete for a growing bacterial population in a chemostat. Computer simulations show that the 2 protozoan populations can coexist over a range of the operating parameters. Some necessary conditions for coexistence are presented as are some speculations regarding the possible physical explanations of results. PMID- 24221051 TI - Contribution by symbiotically luminous fishes to the occurrence and bioluminescence of luminous bacteria in seawater. AB - Seawater samples from a variety of locations contained viable luminous bacteria, but luminescence was not detectable although the system used to measure light was sensitive enough to measure light from a single, fully induced luminous bacterial cell. When the symbiotically luminous fishCleidopus gloriamaris was placed in a sterile aquarium, plate counts of water samples showed an increase in luminous colony-forming units. Luminescence also increased, decreasing when the fish was removed. Light measurements of water samples from a sterile aquarium containingPhotoblepharon palpebratus, another symbiotically luminous fish, whose bacterial symbionts have not been cultured, showed a similar pattern of increasing light which rapidly decreased upon removal of the fish. These experiments suggest that symbiotically luminous fishes release brightly luminous bacteria from light organs into their environment and may be a source of planktonic luminous bacteria. Although planktonic luminous bacteria are generally not bright when found in seawater, water samples from environments with populations of symbiotically luminous fish may show detectable levels of light. PMID- 24221052 TI - Microbial colonization of rat colonic mucosa following intestinal perturbation. AB - An allochthonous population of spiral-shaped bacteria was found colonizing the surfaces of the colonic mucosa of rats after they had been given magnesium sulphate (MgSO4)-induced diarrhea. These organisms were rarely seen in normal control rats and were not displaced when the treatment was ceased, remaining associated with the tissue for periods of up to 180 days. Similar bacteria were also found when specific pathogen-free rats, lacking mucosa-associated populations, were inoculated with homogenized rat intestine from conventional animals. Light and electron microscopic observations showed that the organisms were attached to the surface of the colon, orientated at right angles to the tissue, with one end inserted into the microvillus border. This is the first report of long-term colonization, following perturbation of the gut ecosystem, of a site on the gastrointestinal mucosa not normally associated with bacteria. The ultrastructure and mode of attachment of these organisms were very similar to that of spiral-shaped bacteria known to associate with the colonic mucosa in monkeys and man. PMID- 24221053 TI - Triple-negative breast cancer possibly transforming into malignant melanoma due to targeted therapy? A case report and review of literature. AB - BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by lacking expression of estrogen receptor and progesterone receptor as well as absence of human epidermal growth factor receptor 2 overexpression and is an aggressive clinical phenotype. PATIENTS AND METHODS: We report the case of a 33-year-old woman who has been treated using a targeted approach for TNBC and developed a malignant melanoma metastasis without any primary. RESULTS AND CONCLUSION: Using targeted therapies, tumors can be treated much more effectively, but up to now, we do not know much about potential adverse reactions. Due to the targeted therapy, tumors may be pressurized for transformation. We call for further investigations to rule out the potential risks of targeted therapy in TNBC. This is the first report of a potential transforming of one tumor entity to another by a targeted therapy. PMID- 24221054 TI - Anorectal malignant melanoma in a hemorrhoidal nodule: a diagnostic and therapeutic problem. AB - Anorectal malignant melanoma (ARMM) is an extremely rare condition, often misdiagnosed and mistreated until development of metastatic disease. Clinical presentation mimicking hemorrhoids is a well-known pitfall. We present a male patient with hemorrhoidal nodules who was referred to the policlinic of dermatology for management of anal pruritus. A dark macule was detected over one of the hemorrhoidal nodules histologically verified as melanoma. Subsequent CT and PET/CT showed lymph nodes involvement and the patient underwent wide local excision (WSE) followed by abdominoperineal resection (APR). The rarity of ARMM does not allow for establishment of a validated staging system, placebo controlled treatment trials and management guidelines adoption. The current treatment for the condition is surgical excision, using different techniques according to the stage of the disease and depth of invasion. The prognosis and overall survival are poor, but recent genetic studies give promising results for molecular targeting. Awareness for this disease is indispensable, as early recognition could result in improved survival and quality of life. PMID- 24221056 TI - Fuzzy clustering analysis in environmental impact assessment - A complement tool to environmental quality index. AB - In spite of rapid progress achieved in the methodological research underlying environmental impact assessment (EIA), the problem of weighting various parameters has not yet been solved. This paper presents a new approach, fuzzy clustering analysis, which is illustrated with an EIA case study on Baoshan Wusong District in Shanghai, China. Fuzzy clustering analysis may be used whenever a composite classification of environmental quality/impact incorporates multiple parameters. In such cases the technique may be used as a complement or an alternative to comprehensive assessment. In fuzzy clustering analysis, the classification is determined by a fuzzy relation. After a fuzzy similarity matrix has been established and the fuzzy relation stabilized, a dynamic clustering chart can be developed. Given a suitable threshold, the appropriate classification can be accomplished. The methodology is relatively simple and the results can be interpreted to provide valuable information to support decision making and improve management of the environment. PMID- 24221055 TI - Surgical treatment of craniofacial fibrous dysplasia in adults. AB - Craniofacial fibrous dysplasia (FD) is a rare disorder that may require neurosurgical expertise for definitive management; however, surgical management of FD in adult patients is uncommon. Although other therapies have been shown to slow progression, the only definitive cure for adult craniofacial FD is complete resection with subsequent reconstruction. The authors review the biological, epidemiologic, clinical, genetic, and radiographic characteristics of adult FD, with an emphasis on surgical management of FD. They present a small series of three adult patients with complex FD that highlights the surgical complexity required in some adult patients with FD. Because of the complex nature of these adult polyostotic craniofacial cases, the authors used neurosurgical techniques specific to the different surgical indications, including a transsphenoidal approach for resection of sphenoidal sinus FD, a transmaxillary approach to decompress the maxillary branch of the trigeminal nerve with widening of the foramen rotundum, and complete calvarial craniectomy with cranioplasty reconstruction. These cases exemplify the diverse range of skull base techniques required in the spectrum of surgical management of adult FD and demonstrate that novel variations on standard neurosurgical approaches to the skull base can provide successful outcomes with minimal complications in adults with complex craniofacial FD. PMID- 24221057 TI - Monitoring of methoxychlor residues in the Athabasca River system in northern Alberta after treatment for control of black fly larval populations. AB - Methoxychlor (2,2-bis(p-methoxyphenyl)-1,1,1-trichloroethane) was used in the Athabasca River in northern Alberta for the control of black fly larvae, Simulium arcticum, during May to July of 1981 to 1987. Samples of river water and sediment were analyzed for methoxychlor residues each year as part of Alberta Environment's program to assess environmental impact and monitor compliance with issued permits. During 1985 fish samples were also collected at various sites downstream and upstream of the point of application of methoxychlor. This paper summarizes the residue data obtained by analysing these fish, sediment and water samples collected from the Athabasca River system during the years 1981 to 1987. PMID- 24221058 TI - Estimating oil spill characteristics from oil heads in scattered monitoring wells. AB - The results are presented of a comparison of four different methods of interpolating observed hydrocarbon depths in monitoring wells, as well as a comparison of different methods of selecting sampling points for interpolation. The results provide criteria for selecting one interpolation method over another, under different scenarios. The methods analyzed are: (1) inverse-distance weighting; (2) punctual kriging; (3) minimum surface curvature; and (4) Akima's quintic polynomial. PMID- 24221059 TI - Optimizing environmental monitoring networks with direction-dependent distance thresholds. AB - In the direction-dependent approach to location modeling developed herein, the distance within which a point of demand can find service from a facility depends on direction of measurement. The approach is effective for environmental location problems in which an underlying process with a prevailing gradient (e.g., wind or water flow) influences the interaction between sites in a modeled field. The utility of the approach is illustrated through an application to groundwater remediation. PMID- 24221060 TI - Chemical composition of the NH3-HNO 3-H 2SO 4-NaCl system in the atmosphere of Athens, Greece. AB - This paper presents a procedure for estimating the distribution of ionic material in the NH3-HNO3-H2SO4-NaCl system and applies this procedure in a particular case. The data used were measurements of HNO3, NH3, NO 3 (-) , SO 4 (-) , NH 4 (+) Cl(-) and Na(+) performed during February 1989 - February 1990 in a central Athens street with high traffic density. According to the procedure, ions combine in the following manner: Na(+) combines preferentially with SO 4 (-) , then with NO 3 (-) , followed by NH 4 (+) with the remaining SO 4 (-) and then with the remaining NO 3 (-) to form bisulphates, sulphates and nitrates. The combination procedure showed that the main constituents of the NH3-HNO3-H2SO4-NaCl system are primarily (NH4)2SO4 and, to a lesser extent, NH4NO3 and NH4HSO4, with mean and maximum concentrations, during morning hours, (NH4)2SO4: 14.5 (max 46.8), NH4NO3: 2.97 (max 23) and NH4HSO4: 1.78 (max 40.6) ug m(-3). Lower concentations of Na2SO4, NaHSO4, NaNO3 and NH4Cl and very low concentrations of H2SO4 are also present, depending on the availability of NaCl. It became apparent from the ionic distribution that there is sufficient NH3 to neutralize the H2SO4 and HNO3. It was also shown that a significant fraction of the HNO3, especially on days with high pollution, occurs as aqueous NO 3 (-) . A number of empirical equations have been proposed, which enable the approximate estimation of the constituents of the NH3-HNO3-H2SO4-NaCl system from air pollution monitoring data and meteorological parameters. PMID- 24221061 TI - Guidelines for evaluating selenium data from aquatic monitoring and assessment studies. AB - It is now possible to formulate diagnostic selenium concentrations in four distinct ecosystem-level components; water, food-chain, predatory fish (consuming fish or invertebrate prey), and aquatic birds. Waterborne selenium concentrations of 2 ug/l or greater (parts per billion; total recoverable basis in 0.45 MU filtered samples) should be considered hazardous to the health and long-term survival of fish and wildlife populations due to the high potential for food chain bioaccumulation, dietary toxicity, and reproductive effects. In some cases, ultra-trace amounts of dissolved and particulate organic selenium may lead to bioaccumulation and toxicity even when total waterborne concentrations are less than 1 ug/l.Food-chain organisms such as zooplankton, benthic invertebrates, and certain forage fishes can accumulate up to 30 ug/g dry weight selenium (some taxa up to 370 ug/g) with no apparent effect on survival or reproduction. However, the dietary toxicity threshold for fish and wildlife is only 3 ug/g; these food organisms would supply a toxic dose of selenium while being unaffected themselves. Because of this, food-chain organisms containing 3 ug/g (parts per million) dry weight or more should be viewed as potentially lethal to fish and aquatic birds that consume them.Biological effects thresholds (dry weight) for the health and reproductive success of freshwater and anadromous fish are: whole body=4 ug/g; skeletal muscle=8 ug/g; liver=12 ug/g; ovaries and eggs=10 ug/g. Effects thresholds for aquatic birds are: liver=10 ug/g; eggs=3 ug/g. The most precise way to evaluate potential reproductive impacts to adult fish and aquatic bird populations is to measure selenium concentrations in gravid ovaries and eggs. This single measure integrates waterborne and dietary exposure, and allows an evaluation based on the most sensitive biological endpoint. Resource managers and aquatic biologists should obtain measurements of selenium concentrations present in water, food-chain organisms, and fish and wildlife tissues in order to formulate a comprehensive and conclusive assessment of the overall selenium status and health of aquatic ecosystems. PMID- 24221063 TI - Production of a triple mutant, chlorophyll-deficient, streptomycin-, and kanamycin-resistant Nicotiana tabacum, and its use in intergeneric somatic hybrid formation with Solanum melongena. AB - In order to produce a triple mutant, sexual crosses between a chlorophyll deficient, streptomycin-resistant mutant of Nicotiana tabacum (SA) and a kanamycin-resistant transformant of N. tabacum (KR.) were carried out. From the offspring of this cross, a triple mutant (KR-SA) was selected. In N. tabacum KR SA, chlorophyll deficiency is due to recessive mutation in the nuclear genome, streptomycin resistance is due to a dominant mutation in the chloroplast genome, and kanamycin resistance is shown to be a dominant nuclear marker. Cell suspension protoplasts of N. tabacum KRSA were fused with callus protoplasts of Solanum melongena by dextran treatment. Somatic hybrid plants were selected for streptomycin resistance and the ability to produce clorophyll in regenerated plants. By using this selection system, green plants were recovered from two colonies. When these green plants were then tested for kanamycin resistance, all analyzed plants carried this trait. In addition, the hybrid nature of these plants was confirmed by investigation of the peroxidase isozyme. The present results show that the use of N. tabacum KR-SA in studies of somatic hybridization makes it possible to select somatic hybrid plants easily and provides information of the N. tabacum genome. PMID- 24221062 TI - Somatic hybridization by microfusion of defined protoplast pairs in Nicotiana: morphological, genetic, and molecular characterization. AB - Somatic hybrid/cybrid plants were obtained by microfusion of defined protoplast pairs from malefertile, streptomycin-resistant Nicotiana tabacum and cytoplasmic male-sterile (cms), streptomycin-sensitive N. tabacum cms (N. bigelovii) after microculture of recovered fusants. Genetic and molecular characterization of the organelle composition of 30 somatic hybrid/cybrid plants was performed. The fate of chloroplasts was assessed by an in vivo assay for streptomycin resistance/ sensitivity using leaf explants (R0 generation and R1 seedlings). For the analysis of the mitochondrial (mt) DNA, species-specific patterns were generated by Southern hybridization of restriction endonuclease digests of total DNA and mtDNA, with three DNA probes of N. sylvestris mitochondrial origin. In addition, detailed histological and scanning electron microscopy studies on flower ontogeny were performed for representative somatic hybrids/cybrids showing interesting flower morphology. The present study demonstrates that electrofusion of individually selected pairs of protoplasts (microfusion) can be used for the controlled somatic hybridization of higher plants. PMID- 24221064 TI - Genetical control and linkage relationships of Isozyme markers in sugar beet (B. vulgaris L.). 2. NADP- and NAD-specific malate dehydrogenases, 6-P-gluconate dehydrogenase, shikimate dehydrogenase, diaphorase and aconitase. AB - The NADP-specific malate dehydrogenase isozymes were controlled by multiple gene systems. Three genes coding for dimeric enzymes segregated in a dependent fashion (NADP-Mdh 1, NADP-Mdh 2, NADP-Mdh 3). A fourth gene (NADP-Mdh 4), also coded for dimers, but was not polymorphic in B. vulgaris. A fifth gene (NADP-Me 1) coded for enzymes active as monomers. Two genes were found to control the main zone of NAD-specific malate dehydrogenase: one coded for dimers (Mdh 1), while a second (Mdh 2) was not polymorphic in the assessions studied. 6-P-Gluconate dehydrogenase was not polymorphic in B. vulgaris; the two types detected on SGE1 electrophoresis were due to developmental expression of the different systems. No genetical segregations could be detected in progeny of crosses of the distinct phenotypes. A shikimate dehydrogenase gene (Skdh 1) that coded for monomers was identified. The diaphorase system was rather complex, but one gene (Dia 1) coding for monomeric enzymes could be identified. Aconitase was found to be controlled by two independent genes (Aco 1, Aco 2), both polymorphic and coding for proteins active as monomers. Tight linkage was found between the genes NADP-Mdh 1, NADP Mdh 2 and NADP-Mdh 3. Linkage was also found between a pollen fertility restorer (Z) and the Mdh 1 gene. The identification of linkage with Aco 1 needs further investigation. R segregated independently from Mdh 1, Aco 1 and Dia 1. Independent segregations were scored for isozyme genes Pgm 2, Icd 1, Ak 1, Gpi 1, Aco 1 and Dia 1. PMID- 24221065 TI - Identification of a short rDNA spacer sequence highly specific of a tomato line containing Tm-1 gene introgressed from Lycopersicon hirsutum. AB - We studied rDNA restriction fragment length polymorphism between two tomato lines used for F1 hybrid seed production: line A, containing the Tm-1 gene responsible for tobacco mosaic virus tolerance introgressed from the wild species Lycopersicon hirsutum, and line B, a tobacco mosaic virus sensitive line. Hybridization patterns led to distinct rDNA maps with two size classes, 10.4 and 10.7 kb, in line A and a single, 8.9-kb class in line B. Size differences were located in the intergenie sequence (IGS). A highly specific 54-bp TaqI fragment was cloned from the line A IGS and used in dot blot experiments to probe total DNA from line A, line B, and their F1 hybrid. It proved capable of discriminating B from A and the hybrid. This probe could thus serve to screen inbreds in commercial seed lots where line A is used as male. This fragment showed 80-90% sequence homology with the 53-bp subrepeats previously characterized in a region of the tomato IGS close to the 25S rRNA gene. Preliminary comparison of rDNA in line A and several wild related species indicated that the L. hirsutum H2 genotype was the closest to line A. rDNA variations between line A and this wild genotype could be explained by recombination during the introgression process involving numerous backcrosses or by an important intraspecific polymorphism. Our results strongly suggest that Tm-1 and the rDNA were introgressed together into tomato from L. hirsutum through linkage drag. PMID- 24221066 TI - Linkage mapping of genes for resistance to leaf, stem and stripe rusts and omega secalins on the short arm of rye chromosome 1R. AB - The genes controlling resistance to three wheat rusts, viz., leaf rust (Lr26), stem rust (Sr31) and stripe or yellow rust (Yr9), and omega-secalins (Sec1), located on the short arm of rye chromosome 1R, were mapped with respect to each other and the centromere. Analysis of 214 seeds (or families derived from them) from testcrosses between a 1BL.1RS/1R heterozygote and 'Chinese Spring' ditelocentric 1BL showed no recombination between the genes for resistance to the three rusts, suggesting very tight linkage or perhaps a single complex locus conferring resistance to the three rusts. The rust resistance genes were located 5.4 +/- 1.7 cM from the Sec1 locus, which in turn was located 26.1 +/- 4.3 cM from the centromere; the gene order being centromere - Sec1 - Lr26/Sr31/Yr9 - telomere. In a second test-cross, using a different 1BL.1RS translocation which had only stem rust resistance (SrR), the above gene order was confirmed despite a very large proportion of aneuploids (45.8%) among the progeny. Furthermore, a map distance of 16.0 +/- 4.8 cM was estimated for SrR and the telomeric heterochromatin (C-band) on 1RS. These results suggest that a very small segment of 1RS chromatin is required to maintain resistance to all three wheat rusts. It should be possible but difficult to separate the rust resistance genes from the secalin gene(s), which are thought to contribute to dough stickiness of wheat-rye translocation lines carrying 1RS. PMID- 24221067 TI - Cytological analysis of tetraploid hybrids between sweet potato and diploid Ipomoea trifida (H. B. K.) Don. AB - Tetraploid F1 hybrids between Ipomoea batatas, sweet potato (2n = 6x = ca. 90), and diploid (2n = 2x = 30) I. trifida (H. B. K.) Don. showed various degrees of fertility reduction. The present study aimed to clarify its causes by cytological analysis of meiotic chromosome behavior in the diploid and sweet potato parents and their tetraploid hybrids. The diploid parents showed exclusively 15 bivalents, and the sweet potato parents exhibited almost perfect chromosome pairing along with predominant multivalent formation. Their hybrids (2n = 4x= 57 63) formed 2.6-5.0 quadrivalents per cell, supporting the autotetraploid nature. The meiotic aberratios of the hybrids were characterized by the formation of univalents, micronuclei, and abnormal sporads (monad, dyad, triad, and polyad). The causes underlying these aberrations were attributed in part to the multivalent formation, and in part to a disturbance in the spindle function. Three hybrids showing serious meiotic aberrations were very low in fertility. The utilization of the sweet potato-diploid I. trifida hybrids for sweet potato improvement is described and, further, the role of interploidy hybridization in the study of the sweet potato evolution is discussed. PMID- 24221068 TI - Selection response for litter size at birth and litter weight at weaning in the first parity in mice. AB - Five 60-pair lines of mice were selected for seven generations for the following criteria: number born alive (LSO), random selection of litters (LC), number born alive divided by the weight of the dam at 9 weeks (LSO/DWT), total litter weight weaned divided by the weight of the dam at 9 weeks (LWT/DWT), and weight of litter weaned (LWT). All traits were measured in the first parity only and litters were not standardized. Realized heritabilities for LSO, LWT, LSO/DWT, and LWT/ DWT were 0.10+/- 0.06, 0.11+/-0.07, 0.22 +/- 0.04, and 0.22 +/- 0.08, respectively. Selection response for the two ratio lines was due to correlated responses in the respective numerators, LSO and LWT, as DWT did not decrease. In terms of improving LWT, selection for LWT/ DWT was three times as effective as selection for LSO/ DWT. PMID- 24221069 TI - The identification of the kappa-casein genotype in Holstein dairy cattle using the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to amplify a 99-bp region from the kappa-casein gene of Holstein dairy cattle which contains nucleotide substitutions that are diagnostic of the two major protein variants of kappa casein. Identity of the amplified product was confirmed by direct sequencing. Digestion of the PCR product with MboII (A-variant specific) or TaqI (B-variant specific) allowed direct determination of the genotype of the animal (homozygous or heterozygous). A total of 58 lactating cows with known kappa-casein phenotype were tested using PCR. In all cases, the measured genotype confirmed the phenotype. We have also tested the genotype of 42 sires that were top ranked for milk yield by the CIAQ (Centre d'insemination artificielle du Quebec). The B allele of kappa-casein which occurred at a frequency of 0.13 among the proven bulls is associated with superior milk for industrial applications. Identification of the kappa-casein genotype by PCR in bulls and calves would provide a means for rapidly changing the frequency of the B-allele in the breeding population by selection. PMID- 24221070 TI - Evolutionary analysis of Pinus densata Masters, a putative Tertiary hybrid : 1. Allozyme variation. AB - Allozyme differentiation at 13 loci was studied in populations of Pinus tabulaeformis, P. densata, and P. yunnanensis from China. It was previously suggested that P. densata represents a Tertiary hybrid between P. tabulaeformis and P. yunnanensis. The observed levels of allozyme variation within and among the investigated species were comparable to those of other conifers. P. tabulaeformis differed markedly from P. yunnanensis with respect to allozyme frequencies, while P. densata was intermediate between the two putative parents. There was evidence of homozygote excess in embryos from all investigated species, as compared to Hardy-Weinberg expectations. The observed allozyme composition of P. densata conformed to earlier morphological and molecular evidence indicating hybrid origin of this taxon. It was proposed that fusion of gene pools from P. tabulaeformis and P. yunnanensis has led to adaptive evolution of a new species, P. densata. PMID- 24221071 TI - Evolutionary analysis of Pinus densata (Masters), a putative Tertiary hybrid. : 2. A study using species-specific chloroplast DNA markers. AB - Restriction fragment analysis and heterologous hybridization of chloroplast (cp) DNA was used to develop species-specific markers for P. tabulaeformis, P. yunnanensis and P. massoniana. Fragment patterns created by the BclI and DraI restriction enzymes and hybridization patterns to the psbC and psbD probes were distinctive among the three species. No intraspecific variation was detected with respect to any of the cpDNA markers developed in this study. The cpDNA markers obtained were subsequently used to examine the parentage of P. densata, a putative Tertiary hybrid between P. tabulaeformis and P. yunnanensis. The analysis demonstrated for the first time that P. densata populations accommodate chloroplast genomes of P. tabulaeformis and P. yunnanensis, which strongly supports earlier suggestions of the hybrid origin of this species. It appears that P. densata represents a stabilized natural hybrid that has become adapted to high mountain environments where neither of the parental species can normally grow. PMID- 24221072 TI - Genetic control and linkage relations of additional isozyme markers in chick-pea. AB - Allozyme polymorphisms of nine enzymes - aspartate aminotransferase (AAT), diaphorase (DIA), esterase (EST), formate dehydrogenase (FDH), beta-galactosidase (GAL), beta-glucosidase (GLU), malate dehydrogenase (MDH), malic enzyme (ME), and peroxidase (PRX) - were described in chick-pea (Cicer L.). Thirteen isozyme loci, Aat-c, Dia-4, Est-2, Est-4, Est-10, Fdh, Gal-2, Gal-3, Gal-4, Glu-3, Mdh-2, Me-2, and Prx-2, were genetically defined. Alleles of each of these isozyme loci expressed codominantly in heterozygotes and exhibited a codominant, single-locus segregation ratio in F2. The loci Est-2, Mdh-2, and Me-1 were expressed only in flower. Linkage relations were determined for these 13 and several previously defined isozyme loci. The following new genetic linkages were identified: Pgm-p (locus for plastid phosphoglucomutase) - Est-10; Ald-p1 (one of the duplicate loci for plastid aldolase) - Glu-3 - Gal-2 - Est-2,3; Gal-3 - Aco-m (locus for mitochondrial aconitase) - Prx-2,3; Gpi-c (locus for cytosolic glucosephosphate isomerase) - Fdh; and Est-4 - Me-1. This study provides further confirmation on the existence of several conserved linkage groups among Cicer, Pisum, and Lens. PMID- 24221073 TI - Pollination in vitro: effects on the growth of pollen tubes, seed set and gametophytic self-incompatibility in Trifolium pratense L. and T. repens L. AB - Growth of pollen tubes and seed set were compared after hand pollination in situ and in vitro in two self-incompatible species, Trifolium pratense and Trifolium repens. Adhesion of pollen grains to the stigma was greater in vitro for both species. After cross-pollination, in vitro culture gave a significant increase in the cumulative growth of pollen tubes in pistils of T. pratense compared to in situ conditions. After selfing in T. repens, pollen tube growth was significantly increased by in vitro culture of florets. Seed set after crossing in situ and in vitro was similar for both species. Seed set after selfing in vitro was not increased in T. pratense. Several genotypes of T. repens were classified as very good, good and poor selfers based on their capacity for seed set following selfing in situ. In vitro pollination increased self seed formation by 1.7-, 18.0 and 31.0-fold for each class, respectively. Ovules located nearest to the style were fertilized more often after selfing than after crossing. PMID- 24221074 TI - Asymmetric somatic hybrids between Lycopersicon esculentum and irradiated Lycopersicon peruvianum : 2. Analysis with marker genes. AB - Asymmetric somatic hybrids of Lycopersicon esculentum and Lycopersicon peruvianum were analysed for the retention of genes and alleles specific for L. peruvianum. The hybrids were obtained by fusion of protoplasts from L. esculentum with those of L. peruvianum (the donor), the latter having been irradiated before fusion with 50, 300 or 1,000 Gy of gamma-rays. The retention of three different types of genes or alleles was analysed. (1) The gene coding for kanamycin resistance, which is dominant and had been introduced in most of the L. peruvianum donor plants by transformation. It was present at one locus in 16 L. peruvianum donor plants and at two loci in one donor plant. (2) The genes coding for acid phosphatase, locus Aps-1, and glutamate oxaloacetate transaminase (GOT); different alleles of these genes are co-dominant and were detected by isozyme analysis. (3) Eighteen single gene morphological markers for which most of the L. esculentum genotypes used were homozygous recessive. Kanamycin resistance from donor plants with one locus was retained in about 50% of the asymmetric 30H hybrids (the donor was irradiated with 300 Gy). L. peruvianum specific alleles of Aps-1 and GOT were present in at least 70% of the hybrids; the retention of donor alleles was lower in 30H- than in 5H-hybrids (donor irradiated with 50 Gy). On average, 73% of the L. peruvianum-specific alleles (one or both) of the morphological markers were detected in the 30H-hybrids. Several of the L. esculentum genotypes used were homozygous recessive for two morphological markers on the same chromosome; in 43% of the 30H-hybrids derived from them, only one of these markers was complemented by the L. peruvianum allele. This is an indication of frequent breakage of the L. peruvianum chromosomes. Several hybrid calli regenerated genotypically different shoots. On the whole, this analyses confirms the conclusion drawn from the cytogenetic and morphological analysis of these asymmetric hybrids, namely that irradiation prior to fusion eliminates the L. peruvianum genome to only a limited extent. PMID- 24221075 TI - DNA variation in tissue-culture-derived rice plants. AB - Regenerants of rice were examined by RFLP analysis to determine the occurrence and extent of somaclonal variation. DNA polymorphisms were observed both among plants regenerated from different callus cultures as well as among sibling plants derived from a single callus. Regardless of the basal medium, a higher degree of genetic instability was found among plants regenerated from callus cultures maintained for longer incubation periods (67 days) than among those from shorter incubation periods (28 days). Detailed analysis showed that in several regenerants, there was a close correlation among those plants exhibiting DNA rearrangements and those with apparent methylation changes. Such alterations were observed with both structural and housekeeping genes. PMID- 24221076 TI - Distribution of Bs1 retrotransposons in Zea and related genera. AB - Thirty-eight accessions from Zea and 20 accessions from related genera were probed for the presence of Bs1, a retrotransposon originally found in maize. All maize and teosinte plants tested show the presence of Bs1 in one to five densely hybridizing bands. The mean copy numbers of Bs1 elements among the maize and teosinte accessions were similar: 2.92 and 3.25, respectively, with no large differences between any subgroups. Most exotic maize samples exhibited two common bands of 7.8 kb and 4.7 kb. Section Zea teosintes (but not teosintes of section Luxuriantes) also show the presence of a common band of the same size as the smaller common band in maize. At reduced stringency, Tripsacum dactyloides exhibited a single hybridizing band at 6.9 kb. Results argue for the evolution of maize from a mexicana or parviglumis teosinte, and the evolution of the Bs1 element within the tribe Andropogoneae. Additionally, recombinant inbred lines were probed for the presence of Bs1, in order to map the chromosomal locations of Bs1 elements in four different maize lines. Two of the recombinant inbred parental lines had an element (Bs1-F) on chromosome 5, while the other two lines had an element (Bs1-S) on chromosome 8. Restriction site polymorphisms have apparently arisen in the vicinity of Bs1-S since its insertion. Segregation analysis of other lines was also performed; the data indicate that Bs1 has the distribution expected of a transposable element, different locations in different lines, and not that of a fixed gene locus. However, the common bands in the Zea mays lines and the recombinant inbred data imply that Bs1 is not highly mobile. PMID- 24221077 TI - Inheritance of some Mendelian factors in intra- and interspecific crosses between Setaria italica and Setaria viridis. AB - The inheritance of seed coat color, pericarp color, polyphenoloxidase activity and bristle, glume, collar, and leaf-base anthocyanic colorations was investigated using intra- and interspecific crosses between Setaria italica and S. viridis. The results were compared to inheritance results obtained by previous authors. In most cases, the inheritance is simple (one or two loci) and data from different crosses (intra- and interspecific) and from different authors can be compared. Two sets of two characters were found to share common loci: the polyphenoloxidase locus is one of the loci responsible for seed coat color, and bristle and glume color are determined by the same two loci. The evolutionary significance of these results is discussed. PMID- 24221078 TI - Species-specific sequences in the genus Solanum: identification, characterization, and application to study somatic hybrids of S. brevidens and S. tuberosum. AB - To aid in the identification and analysis of somatic hybrids between potato (Solanum tuberosum, dihaploid line PDH 40) and the non tuber-bearing wild species S. brevidens, a series of species-specific repetitive DNA sequences have been isolated. This was accomplished by making libraries of HaeIII-digested total DNA of S. tuberosum and S. brevidens, by cloning fragments into the SmaI site of plasmid pUC18 and transforming them into E. coli (JM83). The S. brevidens library consisted of 1,000 recombinant clones, and that of S. tuberosum, 700. Nitrocellulose filters with recombinant clones were hybridised to nick-translated total DNA of S. brevidens and also S. tuberosum, and, following autoradiography, clones that hybridised strongly to the DNA of only one of the species were chosen. Two highly repeated S. brevidens clones (pSB1, 400 bp and pSB7,210 bp), one highcopy-number s. tuberosum clone (pST10, 200 bp) and one low-copy-number sequence of S. tuberosum (pST3, 1.5 kbp) were selected for further analysis by Southern hybridisation to digested total DNA. Clone pSB7 gave a ladder pattern on hybridisation to EcoR1-digested total DNA of S. brevidens, with signals at multiples of 200 bp DNA. Using these probes it was possible to verify the hybridity of putative hybrids of dihaploid S. tuberosum and S.brevidens, and to confirm by Southern analysis and by slot blots the parental genome dosage of hexaploid hybrids (two s. brevidens: one S. tuberosum, and vice-versa). The S. tuberosum-specific probe, pSTIO, hybridised with DNA of three other tuber-bearing wild species (S. hjertingii, S. capsicibaccatum and S. berthaultii). A squash blot procedure was developed using the probes that would allow early identification of somatic hybrid callus. There are a number of useful applications of such species-specific probes in the identification and analysis of somatic hybrids. PMID- 24221079 TI - An En (Spm) -system insertion partly reduces the color-suppressing potency of the dominant C-I allele in maize. AB - Two mutable C-I alleles, C-Im857059 and C-Im857062 of the Enhancer-Inhibitor (En I) or Suppressormutator (Spm) transposable-element system, were shown to express a sectored phenotype (colorless sectors on a colored background). This sectoring is a consequence of an I receptor element at the C-I allele responding to an independently segregating, transactive En element. The I element insertion results in the partial reduction of the suppressive potency of the normal C-I alleles. A wide range of suppressive potencies of these two C-Im(r) alleles was found when tested against other C alleles, including C-S and C. Though each of the C-Im(r) alleles has a standard I element, there is a significant difference in the suppressive potencies of the two C-Im(r) alleles, which possibly indicates a different position of the I insert in the coding region affecting the C-I transcript. PMID- 24221080 TI - Expression of the catalase and superoxide dismutase genes in mature pollen in maize. AB - The expression of the Cat and Sod genes encoding the multiple catalases and superoxide dismutases in maize has been studied in maize pollen at anther dehiscence. Pollen from three catalase activity variant inbred lines was examined. Zymorgram analysis, immunoassays, and RNA blots show that, in the lines used, only the CAT-1 catalase isozyme is expressed in mature pollen; the CAT-2 and CAT-3 isozymes are not. The data presented further demonstrate that the Cat1 gene is transcribed and translated after tetrad formation. The relative protein levels of the various superoxide dismutase (SOD) isozymes appear to be similar in pollen and scutella, and correspond to the relatively low levels observed for the different Sod transcripts in these tissues. The presence of "double" transcripts for Sod3 and Sod4A is discussed. PMID- 24221081 TI - Inheritance of height and maturity in crosses between pearl millet landraces and inbred Tift 85DB. AB - Over 300 landraces of pearl millet were collected in Burkina Faso and grown at the Coastal Plain Experiment Station in Tifton/GA. At Tifton, these landraces are predominantly tall and late-maturing. The photoperiod requirements of these landraces hinder evaluation of their performance in the field and their use in breeding programs. A conversion program has been initiated to transfer genes for dwarf stature and early flowering into the tall, late-maturing landraces. The inbred Tift 85DB is being used as a donor of genes for the dwarf and early characteristics, and was crossed to nine randomly selected landraces from Burkina Faso. The parents, F1, F2, and backcrosses to each parent were grown in the field and evaluated for plant height at anthesis and time in days from planting to anthesis. In general, plant height of F1s was taller than the tallest parent, and in all crosses the maturity of F1s was intermediate between the parents. Numbers of loci conferring height varied among crosses, ranging from 0 to 9.6, and averaged 1.6. Estimated numbers of loci conferring maturity ranged from 0 to 12.8 and averaged 3.4. Broad-sense heritability estimates for height and maturity averaged 60.2 and 65.7%, respectively. Corresponding narrow-sense estimates averaged 23.8 and 48.2%. Joint scaling tests revealed that additive-genetic effects were highly significant for both traits, but dominance and epistatic genetic effects contributed to the inheritance of each trait in some crosses. The low gene numbers, high heritability estimates, and preponderance of additive genetic effects suggest that selection for these traits should be effective. PMID- 24221082 TI - Nitrogen storage dynamics are affected by masting events in Fagus crenata. AB - It is generally assumed that the production of a large crop of seeds depletes stores of resources and that these take more than 1 year to replenish; this is accepted, theoretically, as the proximate mechanism of mast seeding (resource budget model). However, direct evidence of resource depletion in masting trees is very rare. Here, we trace seasonal and inter-annual variations in nitrogen (N) concentration and estimate the N storage pool of individuals after full masting of Fagus crenata in two stands. In 2005, a full masting year, the amount of N in fruit litter represented half of the N present in mature leaves in an old stand (age 190-260 years), and was about equivalent to the amount of N in mature leaves in a younger stand (age 83-84 years). Due to this additional burden, both tissue N concentration and individual N storage decreased in 2006; this was followed by significant replenishment in 2007, although a substantial N store remained even after full masting. These results indicate that internal storage may be important and that N may be the limiting factor for fruiting. In the 4 years following full masting, the old stand experienced two moderate masting events separated by 2 years, whilst trees in the younger stand did not fruit. This different fruiting behavior may be related to different "costs of reproduction" in the full masting year 2005, thus providing more evidence that N may limit fruiting. Compared to the non-fruiting stand, individuals in the fruiting stand exhibited an additional increase in N concentrations in roots early in the 2007 growing season, suggesting additional N uptake from the soil to supply resource demand. The enhanced uptake may alleviate the N storage depletion observed in the full masting year. This study suggests that masting affects N cycle dynamics in mature Fagus crenata and N may be one factor limiting fruiting. PMID- 24221083 TI - Do climate and soil influence phenotypic variability in leaf litter, microbial decomposition and shredder consumption? AB - We tested the hypothesis that water stress and soil nutrient availability drive leaf-litter quality for decomposers and detritivores by relating chemical and physical leaf-litter properties and decomposability of Alnus glutinosa and Quercus robur, sampled together with edaphic parameters, across wide European climatic gradients. By regressing principal components analysis of leaf traits [N, P, condensed tannins, lignin, specific leaf area (SLA)] against environmental and soil parameters, we found that: (1) In Q. robur the condensed tannin and lignin contents increased and SLA decreased with precipitation, annual range of temperature, and soil N content, whereas leaf P increased with soil P and temperature; (2) In A. glutinosa leaves N, P, and SLA decreased and condensed tannins increased with temperature, annual range of temperature, and decreasing soil P. On the other hand, leaf P and condensed tannins increased and SLA decreased with minimum annual precipitation and towards sites with low temperature. We selected contrasting leaves in terms of quality to test decomposition and invertebrate consumption. There were intraspecific differences in microbial decomposition rates (field, Q. robur) and consumption by shredders (laboratory, A. glutinosa). We conclude that decomposition rates across ecosystems could be partially governed by climate and soil properties, affecting litter quality and therefore decomposers and detritivores. Under scenarios of global warming and increased nutrients, these results suggest we can expect species-specific changes in leaf-litter properties most likely resulting in slow decomposition with increased variance in temperatures and accelerated decomposition with P increase. PMID- 24221084 TI - TDAG8 activation inhibits osteoclastic bone resorption. AB - Although the roles of acids in bone metabolism are well characterized, the function of proton-sensing receptors in bone metabolism remains to be explored. In this study, we evaluated the role of proton-sensing receptor T-cell death associated gene 8 (TDAG8) in osteoclastic activity during bone loss after ovariectomy. Through observations of bone mineral content, we found that pathological bone resorption was significantly exacerbated in mice homozygous for a gene trap mutation in the Tdag8 gene. Furthermore, osteoclasts from the homozygous mutant mice resorbed calcium in vitro more than the osteoclasts from the heterozygous mice did. Impaired osteoclast formation under acidic conditions was ameliorated in cultures of bone marrow cells by Tdag8 gene mutation. Extracellular acidification changed the cell morphology of osteoclasts via the TDAG8-Rho signaling pathway. These results suggest that the enhancement of TDAG8 function represents a new strategy for preventing bone resorption diseases, such as osteoporosis. PMID- 24221085 TI - Ethanol contributes to neurogenic pancreatitis by activation of TRPV1. AB - Alcohol abuse is a major cause of pancreatitis in people, but the mechanism is unknown. It has been recently demonstrated that transient receptor potential vanilloid 1 (TRPV1) activation causes neurogenic inflammation and plays an important role in acute pancreatitis. Moreover, TRPV1 is activated by ethanol. We examined the direct effects of ethanol on acute pancreatitis. Acute inflammation of the pancreas was produced by injection of ethanol and palmitoleic acid (POA), a nonoxidative metabolite of ethanol, in wild-type C57BL/6J mice and Trpv1 knockout C57BL/6J mice. Inflammatory indexes were analyzed 24 h later. Injection of ethanol + POA produced acute pancreatitis indicated by significant increases in histopathological damage, serum amylase levels, and pancreatic MPO concentrations (P<0.05-0.001). All parameters of pancreatitis were blocked by pretreatment with the TRPV1 antagonist drug AMG9810. In addition, ethanol + POA administration to Trpv1knockout mice did not produce pancreatic inflammation. Treatment with vehicle, ethanol alone, or POA alone had no inflammatory effects. TRPV1 partially mediates inflammation induced by ethanol + POA in the mouse pancreas, consistent with the ability of ethanol to activate TRPV1. We propose that ethanol may contribute to alcohol-induced pancreatitis by a neurogenic mechanism. PMID- 24221086 TI - An NT4/TrkB-dependent increase in innervation links early-life allergen exposure to persistent airway hyperreactivity. AB - Children who are exposed to environmental respiratory insults often develop asthma that persists into adulthood. In this study, we used a neonatal mouse model of ovalbumin (OVA)-induced allergic airway inflammation to understand the long-term effects of early childhood insults on airway structure and function. We showed that OVA sensitization and challenge in early life led to a 2-fold increase in airway smooth muscle (ASM) innervation (P<0.05) and persistent airway hyperreactivity (AHR). In contrast, OVA exposure in adult life elicited short term AHR without affecting innervation levels. We found that postnatal ASM innervation required neurotrophin (NT)-4 signaling through the TrkB receptor and that early-life OVA exposure significantly elevated NT4 levels and TrkB signaling by 5- and 2-fold, respectively, to increase innervation. Notably, blockade of NT4/TrkB signaling in OVA-exposed pups prevented both acute and persistent AHR without affecting baseline airway function or inflammation. Furthermore, biophysical assays using lung slices and isolated cells demonstrated that NT4 was necessary for hyperreactivity of ASM induced by early-life OVA exposure. Together, our findings show that the NT4/TrkB-dependent increase in innervation plays a critical role in the alteration of the ASM phenotype during postnatal growth, thereby linking early-life allergen exposure to persistent airway dysfunction. PMID- 24221088 TI - The effect of temperature on the growth ofCandida sake isolated from the leaves of a subantarctic grass. AB - During a survey of microfungi on the subantarctic island of South Georgia, large numbers of phylloplane yeasts were isolated in late spring from leaves of a tussock grass. The dominant yeast was identified asCandida sake, this being the first record for the Antarctic region. Isolates in liquid culture had a temperature optimum for growth of 20-25 degrees C. It was capable of assimilation of a range of simple carbohydrates, similar to those found in leachates from new leaves of the tussock grass. The seasonal decline of yeasts on the phylloplane is discussed in terms of the availability of leachate and the growth of filamentous microfungi on new leaves. PMID- 24221089 TI - The maintenance ofBdellovibrio at low prey density. AB - A mathematical model for the interaction ofBdellovibrio and its prey predicted that a relatively high prey density (7*10(5) cells ml(-1)) would be required for the establishment of an equilibrium in a mixed population [8]. The present report shows thatBdellovibrio can be maintained in a continuous culture when the prey cell density is much lower (2-5*10(4) cells ml(-1)), and closer to that of naturally occurring bacterial populations in sea waters. PMID- 24221087 TI - Sustained delivery of proangiogenic microRNA-132 by nanoparticle transfection improves endothelial cell transplantation. AB - Transplantation of endothelial cells (ECs) for therapeutic vascularization or tissue engineering is a promising method for increasing tissue perfusion. Here, we report on a new approach for enhanced EC transplantation using targeted nanoparticle transfection to deliver proangiogenic microRNA-132 (miR-132) to cultured ECs before their transplantation, thereby sensitizing cells to the effects of endogenous growth factors. We synthesized biodegradable PLGA polymer nanoparticles (NPs) that were loaded with miR-132 and coated with cyclic RGD (cRGD) peptides that target integrin alphavbeta3 expressed on cultured human umbilical vein ECs (HUVECs), increasing NP uptake through clathrin-coated pits. Unlike previously reported NPs for miR delivery, these NPs slowly release RNA for several weeks. The endocytosed NPs remain in clathrin-coated vesicles from which they mediate intracellular delivery of siRNA or miRNA. Transfection of HUVECs with miR-132 enhances growth factor-induced proliferation and migration in 2D culture, producing a 1.8- and 5-fold increase, respectively. However, while the effects of conventional transfection were short-lived, NP transfection produced protein knockdown and biological effects that were significantly longer in duration (>= 6 d). Transfection of HUVECs with miR-132 NP resulted in a 2-fold increase in the number of microvessels per square millimeter compared to lipid after transplantation into immunodeficient mice and led to a higher number of mural cell-invested vessels than control transfection. These data suggest that sustained delivery of miR-132 encapsulated in a targeted biodegradable polymer NP is a safe and efficient strategy to improve EC transplantation and vascularization. PMID- 24221090 TI - Comparative study of the growth of two strains ofNitrobacter in batch and continuous culture. AB - Growth kinetics of 2Nitrobacter strains (N.w. and L) coexisting in the same soil are studied in batch and continuous culture. Monod's parameters are estimated numerically from experimental data in the case of the batch experiment, and from steady-state equations in the case of the chemostat. In both cases, the 2 strains show different values for their growth parameters. N.w. may be characterized by its highMU max-Ks values, relative to strain L. But for each strain,MU max is significantly lowered between batch and continuous culture. In this latter case, at N-NO2 (-) concentrations less than 1.5MUg.ml(-1), the 2 strains exhibit similar growth rates showing that for concentrations of the limiting substrate prevailing in the soil, they may compete for this substrate. PMID- 24221091 TI - Nitrous oxide production by nitrogen-fixing, fast-growing Rhizobia. AB - Rhizobium trifolii, R. leguminosarum, andR. "hedysarum", grownex planta under anoxic conditions in a chemically defined medium, evolve N2O from NO3 (-), NO2 ( ), and (NH4)2NO3. The amount of nitrous oxide formed after 96 hours is about 0.2MUM*mg(-1) cells d.w. Large availability of organic matter enhances the production of N2O from nitrate by free-livingR. trifolii in peat/sand mixtures. Denitrification of the above species andR. meliloti was detected also in planta. Nitrous oxide production increases almost linearly from 10-45MUM*mg(-1) nodules d.w. when nitrogen-fixing plants are exposed to increasing concentrations of nitrate (1-12MUM). PMID- 24221092 TI - Catalase and sulfur in the rice rhizosphere: An ultrastructural histochemical demonstration of a symbiotic relationship. AB - An ultrastructural study has been made of a symbiotic association between a sulfur bacterium and the roots of the rice plant (Oryza saliva L.). This association is proposed to have useful economic consequences in ameliorating hydrogen sulfide toxicity and associated Akiochi or Straighthead disease in lowland rice cultivation. The presence of catalase (E.C. 1.11.1.6) in rice roots and in some rhizosphere bacteria has been demonstrated in ultrathin sections of field-grown rice using a catalasespecific medium. Catalase was detected in capsules surrounding the catalase-negative S-bacteria. These capsules were of a novel fibrillar structure. Two sizes of inclusion bodies were present in these large bacteria. The disappearance of the smaller inclusions during carbon disulfide treatment suggests that they are the sulfur granules. The name "thiosome" is proposed for these membrane-bound structures. PMID- 24221093 TI - Studies on the ecology of West Australian actinomycetes: Factors which influence the diversity and types of actionomycetes in Australian soils. AB - A statistical technique has been employed to study the effects of various environmental factors in altering the actinomycete populations of soils located in the western part of Australia. Over 12,000 actinomycetes obtained at 28 different locations were included in the evaluation. Among factors that had a significant influence were the geographic area at which the sample was taken, the nature of plant rhizosphere, and a rainstorm. Seasonal changes in population did occur, but there was considerable stability of population with time. Although marked differences occurred in types of actinomycetes present among different geographic locations, multiple samples taken within a location at distances of 30 cm or greater showed marked similarity in populations. There were varied degrees of diversity among the populations studied. The population that developed after a rainstorm was low in diversity, whereas the populations of root rhizospheres were as diverse as those of plant-free soil-litter areas. In assessing the ecology of soil actinomycetes, it is important to consider the degree of change in population induced by an environmental factor and also its effect on diversity, since the effects may be complementary or may be opposite in nature. PMID- 24221094 TI - Measuring microzooplankton grazing on planktonic marine bacteria by its impact on bacterial production. AB - Grazing on planktonic bacteria by microzooplankton was estimated by separating bacteria from the larger plankton with 1MUm pore Nuclepore filtration and measuring changes in bacteria in filtered and unfiltered samples over 24 hours. In the absence of grazers, bacteria increased linearly. The regression coefficient of linear increase was used to estimatein situ bacterial production. When grazers were present, the changes in bacteria concentration usually took the form of a linear decline, and grazing was estimated by subtracting the regression coefficient of the unfiltered sample from that of the 1MUm filtrate. Results from the Essex estuary-coastal system of northern Massachusetts show grazing and production at rates that indicate a daily turnover of the standing crop of bacteria, with highest values in mid-estuarine waters. Experiments on the size distribution of grazing showed that microzooplankton from 1-3MUm were responsible for most of the observed decrease in bacteria. It was suggested that the basic pattern of linear increase of the bacteria in the absence of grazing reflects density-dependent limitation by substrate present at the outset of the incubation and is indicative of a population that has been maintained around the mid-point of the logistic growth curve by grazing. PMID- 24221095 TI - Observations on microbial percent respiration values in arctic and subarctic marine waters and sediments. AB - Percent respiration was measured in over 1,100 arctic and subarctic marine water and sediment samples using(14)C-labeled glucose and glutamate. These measurements were made at different times of the year in 4 regions. Percent respiration values were typically lower in regions where the waters of large rivers mixed with seawater. They were also lower in sediments and in waters collected near the bottom than in surface waters. They were higher in winter arctic waters than water samples collected in the summer; however, a similar seasonal trend was not observed in subarctic waters. There were a number of studies in which there were significant positive rank correlations between percent respiration and salinity and between percent respiration and temperature. From what is known about the range of temperature and salinity encountered in samples collected during these studies and the results of temperature and salinity effects experiments, it was concluded that changes in these 2 variables did not explain the variation observed in percent respiration. Correlations between percent respiration and the inorganic nutrients PO4 (-3), NH4 (+) and NO3 (-) showed that of the 3 variables, only NO3 (-) showed relatively high correlations with all the same sign. From this it was concluded that there may be situations in which NO3 (-) levels may influence percent respiration in nearshore marine waters. It is also likely that qualitative characteristics of the available organic nutrients may also influence percent respiration levels. Although no organic nutrient data is available for statistical analysis, the patterns of percent respiration near river plumes and the relatively strong negative correlation often observed between uptake rates (heterotrophic activity) and percent respiration suggests that organic nutrients may be a factor in controlling percent respiration. It is suggested that there are situations in which percent respiration measurements may be used to document stress in natural microbial populations due to nutrient deficiencies. PMID- 24221096 TI - Simultaneous estimation ofV max, K m, and the rate of endogenous substrate production (R) from substrate depletion data. AB - The nonlinear and 3 linearized forms of the integrated Michaelis-Menten equation were evaluated for their ability to provide reliable estimates of uptake kinetic parameters, when the initial substrate concentration (S0) is not error-free. Of the 3 linearized forms, the one where t/(S0-S) is regressed against ln(S0/S)/(S0 S) gave estimates ofV max and Km closest to the true population means of these parameters. Further, this linearization was the least sensitive of the 3 to errors (+/-1%) in S0. Our results illustrate the danger of relying on r(2) values for choosing among the 3 linearized forms of the integrated Michaelis-Menten equation. Nonlinear regression analysis of progress curve data, when S0 is not free of error, was superior to even the best of the 3 linearized forms. The integrated Michaelis-Menten equation should not be used to estimateV max and Km when substrate production occurs concomitant with consumption of added substrate. We propose the use of a new equation for estimation of these parameters along with a parameter describing endogenous substrate production (R) for kinetic studies done with samples from natural habitats, in which the substrate of interest is an intermediate. The application of this new equation was illustrated for both simulated data and previously obtained H2 depletion data. The only means by whichV max, Km, and R may be evaluated from progress curve data using this new equation is via nonlinear regression, since a linearized form of this equation could not be derived. Mathematical components of computer programs written for fitting data to either of the above nonlinear models using nonlinear least squares analysis are presented. PMID- 24221097 TI - Applicability of the fluorescein diacetate method of detecting active bacteria in freshwater. AB - Fluorescein diacetate (FDA) hydrolysis was evaluated as a means to detect actively metabolizing bacteria in freshwater. Fluorescein diacetate, a nonfluorescent derivative of fluorescein, can be transported across cell membranes and deacetylated by nonspecific esterases. Resultant fluorescein accumulates within cells and allows direct visualization by epifluorescent microscopy. Application of FDA to a variety of freshwater habitats yielded estimates of active cells ranging from 6-24% of the total population. These estimates were 49-61% lower than estimates of active cells obtained from measures of electron transport activity. The difference was attributed to low permeability of the fluorogen through the outer membrane of heterotrophic gram-negative cells. Data suggest that FDA hydrolysis as a means of detecting active bacteria may be limited to environments rich in eucaryotes and gram-positive cells. PMID- 24221098 TI - Effects of interferential care: a community-based care program for persons with severe problems on several life areas. AB - BACKGROUND AND AIMS: Interferential care differs from the current community-based care programs in that it targets a larger, heterogeneous group and combines brokerage and full service elements in a multi-organizational care team. The team provides all the services itself, but with the aim to prepare clients within a few months for referral to regular (ambulant) healthcare services. The aim of this study was to assess the effectiveness of interferential care. METHODS: In a multisite, pretest-posttest design, 523 patients of three interferential care teams were followed. Quality of life, problem severity, problems with referral and engagement were assessed at baseline, at referral and again after 6 months. Analyses were performed using linear mixed modeling. RESULTS: Interferential care showed moderate to strong effects on quality of life and problem severity. These effects persisted (quality of life) or further improved (problem severity) until follow-up 6 months after referral to regular services. There were also small effects on both engagement and problems with referral. CONCLUSION: Interferential care offers significant improvements in quality of life and problem severity in persons who have severe problems on several life areas and who are currently not reached by healthcare services. It is a promising community-based care program for healthcare systems in which regular care already contains many elements of home-based practice. PMID- 24221099 TI - Recommendations of the Sardinian public for the treatment of depression. AB - BACKGROUND: Public beliefs about appropriate treatment impact, help-seeking and treatment adherence. AIM: To determine the recommendations of the Sardinian public for the treatment of depression. METHODS: In 2012, a population-based survey was conducted by phone in Sardinia (N = 1,200). In the context of a fully structured interview, respondents were presented with a vignette depicting a case of depression. Subsequently, they were asked about their treatment recommendations. The results are contrasted with findings from a similar survey which had been conducted in Vienna 3 years before. RESULTS: In Sardinia as in Vienna, psychotherapy was the uncontested favorite, while antidepressant medication was recommended by relatively few respondents. In Sardinia, there were also no marked differences between urban and rural areas with regard to these two treatments. However, between Sardinia and Vienna, as well as within Sardinia, great differences were found with regard to autogenic training and 'alternative' methods like homeopathic medicines and acupuncture. CONCLUSION: Cross-cultural comparisons may help better understand treatment preferences of the public. In Sardinia, as in Vienna, there seems to be a need for improving the public's knowledge about the appropriate treatment of depression. PMID- 24221100 TI - An improved system to obtain fertile regenerants via maize protoplasts isolated from a highly embryogenic suspension culture. AB - Regenerants from a 30-month-old haploid and a 10-month-old diploid tissue culture were cross-pollinated to generate a synthetic genotype (HE/89) with improved competence for maintenance of totipotency in various cultured expiants. The HE/89 zygotic embryos developed friable, embryogenic cultures in the commonly used MS and N6-based media without the addition of L-proline. By optimalization and changing the culture conditions, we were able to regulate the maintenance of the earlier, more synchronous (Type II) and the later, asynchronous (Type I) in vitro embryogenesis, as well as the shift between different ontogenic stages. Within 70 days after the inoculation of immature embryos a relatively homogeneous, early embryogenic suspension culture usable for protoplast isolation was established from the initially surface-grown cultures. Using modified solutions for protoplast isolation and culture, viable protoplasts were reproducibly obtained from which plants were regenerated via defined ontogenic steps. Despite the long in vitro history of the parental genotypes, 60-70% of the more than 500 plants derived from the HE/89 protoplasts set seeds following self or sib-pollination. PMID- 24221101 TI - Chloroplast DNA polymorphism in fertile and male-sterile cytoplasms of sorghum (Sorghum bicolor (L.) Moench). AB - Restriction endonuclease patterns of chloroplast DNA (cpDNA) were consistently distinguishable between fertile and male-sterile cytoplasms of sorghum [Sorghum bicolor (L.) Moench], whereas no differences in restriction patterns of cpDNA among male-sterile (A1) lines, including six isocytoplasmic strains, were revealed in this study. It is suggested that chloroplast DNA may contribute to the male sterility of A1 lines used currently in hybrid sorghum production. PMID- 24221102 TI - Variation in a single protoplast- and seed-derived population of Lotus corniculatus L. AB - Lotus comiculatus L. is a widely cultivated, outbreeding, leguminous forage crop. Seventy-one plants, most of which were tetraploid, were regenerated from calli derived from a single protoplast. Their morphological and agronomic traits were evaluated and compared with those of the seed-produced population. The variances of most of the traits in the protoplast-derived (protoclonal) population were smaller than those of the seed-produced population. Mean values of all the traits of the protoclonal population shifted significantly towards lower values. However, new phenotypic variants with higher values than those of the plant initially used for protoplast isolation were also observed. Plants with less hydrocyanic acid (which has a toxic effect on cattle) than the initial plant were obtained in the protoclones. Generally, the pollen fertility of protoclones was significantly low compared with the seed-produced plants. This seems to be partly due to the occurrence of abnormalities in chromosome structure during protoplast and/or callus culture, as suggested by the formation of univalents, lagging, and fragment chromosomes and bridges at metaphase I and anaphase I and II of the regenerants. The changes in chromosome structure, however, did not induce any malformed morphologies. PMID- 24221103 TI - Introgression of genes from Oryza officinalis Well ex Watt to cultivated rice, O. sativa L. AB - Sterile AC hybrids between cultivated Oryza sativa (AA) and a distant wild species, O. officinalis (CC), were backcross to O. sativa. Most of the BC1 progenies were allotriploid (AAC), a few were hypotriploid. AAC progenies were again backcrossed to O. sativa. BC2 progenies consisting of disomic or aneuploid individuals were examined for the presence of O. officinalis traits. Eleven different traits from O. officinalis were identified in these progenies. Segregation data in the subsequent generations suggest that these traits are monogenic in nature. Two of these genes - for resistance to BPH and WBPH - are of value in rice improvement. The extremely low recovery of recombinant progenies is in agreement with the very low amount of pairing between A and C genomes. Because of this restricted recombination, the genotype of the recurrent parent was reconstituted after two backcrosses only. Thus, the BC2 progenies look remarkably similar to O. sativa. Most of them are stable and fertile and also interfertile with other O. sativa breeding lines. Some of the BPH-and WBPH-resistant progenies are comparable in yield to the best O. sativa parents and are being evaluated as varietal possibilities. PMID- 24221104 TI - Effect of selection on genetic parameters of correlated traits. AB - Changes in genetic parameters of correlated traits due to the buildup of linkage (gametic phase) disequilibrium from repeated truncation selection on a single trait are studied. After several generations of selection, an equilibrium is approached where there are no further changes in genetic parameters and limiting values are reached. Formulae are derived under an infinitesimal model for these limiting values of genetic variances and covariances, heritabilities, and genetic correlations between traits directly and indirectly selected. Changes from generation zero to the limit in all these parameters become greater as heritability of the trait under direct selection increases and, to a lesser extent, as intensity of selection increases. Change in heritability of a trait under indirect selection also increases as the absolute value of the correlation between the trait under indirect and the trait under direct selection increases. The change is maximum when the initial value of heritability is close to 0.5 and insignificant when the initital value is close to zero or one. Change in the genetic correlation between the trait under direct selection and the trait under indirect selection is maximum when its initial value is close to +/-0.6 and insignificant when its initial value is close to zero or +/-1. Heritability of the trait indirectly selected and genetic correlation between that trait and the trait directly selected always decrease in absolute value, whereas genetic correlation between two traits indirectly selected can either decrease or increase in absolute value. It is suggested that use be made of formulae at selection equilibrium in the prediction of correlated responses after several generations of selection. PMID- 24221105 TI - Mitochondrial DNA polymorphisms of Malawian bean lines: further evidence for two major gene pools. AB - Intraspecific mitochondrial DNA (mtDNA) diversity was determined in 23 Phaseolus vulgaris genotypes, and compared to previously observed variability of morphoagronomic characters and isozyme loci. Twenty of the lines were collected from Malawian landraces; the other three were pure-bred cultivars. The mtDNAs were digested with eight restriction endonucleases, revealing complex banding patterns. Southern hybridization using cosmid clones covering about 200-kb of the genome showed a considerable amount of uniformity of the mtDNA banding patterns. However, five restriction fragment length polymorphisms (RFLPs) were detected, dividing the bean lines into two groups corresponding to the previously known Mesoamerican and Andean gene pools of P. vulgaris. The cultivar "Mecosta" was separated from the rest of the lines by an additional RFLP. At least two out of the six RFLPs are believed to be due to base-pair mutation events. Our results provide the first evidence that the cytoplasms of the two major germ plasm pools of beans are distinct. PMID- 24221106 TI - Quantitative phenotypical expression of three mutant genes in barley and the basis for defining an ideotype for Mediterranean environments. AB - Three mutants induced in the two-rowed barley variety Beka and their three binary recombinants have been used in an attempt to define an ideotype suitable for Mediterranean agroclimatic conditions. Physiological methods (classical plant growth analysis) together with the study of genotype x environment interaction for grain yield were used to characterize the genotypes. That characterization brought out the huge phenotypical variation produced by only three mutant genes, suggesting that single Mendelian genes may alone explain the quantitative variation, including grain yield, without the necessity of using the polygenic concept. The genotype best adapted to the environments studied is later in heading and has shorter straw and denser spikes than Beka; it also has higher inverse of leaf area rate and grain: leaf area ratio, a lower rate of leaf senescence, and a shorter grain filling period than the original variety. PMID- 24221107 TI - Relationship between gene expression and hybrid vigor in primary root tips of young maize (Zea mays L.) plantlets. AB - To provide an insight into the molecular basis of heterosis, we investigated gene expression in primary root tips of a heterotic maize hybrid (B73 * Mo17) and its parental lines (B73 and Mo17). This analysis was carried out (i) by differential plaque hybridization of a recombinant cDNA library made to poly(A) RNA isolated from B73 * Mo17 primary root tips, and (ii) by comparing with two-dimensional gel electrophoresis proteins synthesized in vitro in the rabbit reticulocyte system by poly(A) RNA isolated, at different stages of development, from the three genotypes. The results showed that there are sets of proteins and mRNAs that are differentially synthesized and expressed in the F1 primary root tips in comparison to the parental lines. Moreover, results from the survey of 21 major in-vitrosynthesized polypeptide variants, from mRNAs of primary root tips of the parental lines and their F1 hybrid, indicated that in seven instances hybrid proteins translated in vitro were more abundant or possibly new. In most of the remaining cases, hybrid spots were similar in intensity to the same protein produced by one of the two parental lines. PMID- 24221108 TI - Analysis of chloroplast and mitochondrial segregation in three different combinations of somatic hybrids produced within Brassicaceae. AB - Mitochondrial and chloroplast DNA were characterized in three different combinations of somatic hybrids produced between different species within Brassicaceae. The fusions were made between B. campestris and B. oleracea, B. napus and B. nigra and between B. napus and Eruca sativa. The combinations represent interspecific hybridizations, but the phylogenetic distance between the species used in each instance is different. Whereas the B. campestris (+) B. oleracea and the B. napus (+)B. nigra hybrids are both examples of intrageneric hybrids, B. campestris is more closely related to B. oleracea than B. napus is to B. nigra. The fusion of B. napus and E. sativa represents an intergeneric hybridization. Since hybrids were produced with reproducible and uniform fusion and culture methods, a comparison of chloroplast and mitochondrial segregation and mitochondrial DNA (mt-DNA) rearrangements could be made between the combinations. The segregation of both chloroplasts and mitochondria was biased in the B. napus (+)B. nigra and the B. napus (+)E. sativa combination. The nonrandom segregation of chloroplasts and mitochondria could be due to the different ploidy levels of the fusion partners and/or reflect differences in organelle replication rate. Furthermore, segregation of mitochondria was correlated to the differences in phylogenetic distance between the species used in the fusions. However, mitochondrial segregation, in contrast to chloroplast segregation, could in all combinations also have been affected by the cell type used as protoplast source in the fusions. All different chloroplast types could be established within each combination. Hybrids containing chloroplast from one parent together with mitochondria from the other parent were found in two of the combinations, although the majority of the hybrids had mt-DNA that was altered compared to the parental species. The rearranged mt-DNA found in most hybrids was an effect of the heteroplasmic state following protoplast fusion rather than of the tissue culture methods, since no mt-DNA rearrangements were found in B. napus plants regenerated from protoplast culture. The mtDNA restriction patterns of the hybrids with rearranged mt-DNA indicated that specific regions of the mt-DNA were involved in the rearrangements following protoplast fusion. PMID- 24221109 TI - Induction of triploid Citrus plants from endosperm calli in vitro. AB - Triploid hybrid Citrus plants were regenerated by somatic embryogenesis in vitro from endosperm derived calli. A sequence of media formulations was used to induce and support proliferation of primary callus from endosperm, to induce embryogenesis from primary callus, and to allow embryo development leading to viable plantlets. Calli were induced from cellular endosperm of Citrus sinensis (sweet orange), C. Xparadisi (grapefruit), and C. grandis (pummelo) excised 12-14 weeks post-anthesis. Induction of embryogenesis from sweet orange and pummelo primary calli required gibberellic acid and double mineral nutrient concentrations. Embryogenesis was not induced from grapefruit calli in these experiments. Only sweet orange embryos developed sufficiently to allow plant regeneration. Triploid axillary buds were minigrafted onto etiolated diploid rootstock seedlings in vitro in order to transfer triploid regenerants to soil and the external environment. Triploidy (2n = 3x = 27) was observed consistently in all phases of regeneration and in recovered plants. These results demonstrate that triploid hybrid plant recovery from Citrus endosperm can overcome barriers to sexual hybridization resulting from apomixis. PMID- 24221110 TI - Genetic mapping between Gli-B1 locus and a telomeric C-heterochromatin band in wheat. AB - Using C-banding it has been possible to prove that the bread wheat varieties 'Holdfast' and 'CapelleDesprez' shows an intense band of telomeric heterochromatin on the short arm of chromosome 1B, while the variety 'Pane-247' presents a very thin band. Gliadin study using pH-acid electrophoresis revealed the existence of differences in the Gli-B1 locus in the three varieties. Analysis of the progeny of the (P x H) x CD hybrid revealed recombination between the heterochromatin C-band and locus Gli-B1, and allowed the genetic distance between the two markers to be calculated as 6.55+/-3.16 cMorgan. This is the first time the genetic distance from a locus to the chromosome telomere has been directly obtained in wheat. The heterochromatin C-band studied here gives us a cytological marker on chromosome 1B that can be used as a reference point in the localization of other genes. PMID- 24221111 TI - Enhanced N2-fixing ability of a deletion mutant of arctic rhizobia with sainfoin (Onobrychis viciifolia). AB - Mutagenesis provoked by exposure at elevated temperature of the cold-adapted, arctic Rhizobium strain N31 resulted in the generation of five deletion mutants, which exhibited loss of their smaller plasmid (200 kb), whereas the larger plasmid (> 500 kb) was still present in all mutants. Deletion mutants did not show differences from the wild type in the antibiotic resistance pattern, the carbohydrates and organic acids utilization, and the growth rate at low temperature. However, deletion mutants differed from the wild type and among themselves in the ex planta nitrogenase activity, the nodulation index, and the symbiotic effectiveness. The deletion mutant N31.6rif (r) showed higher nodulation index and exhibited higher nitrogenase activity and symbiotic efficiency than the other deletion mutants and the wild type. The process of deletion mutation resulted in the improvement of an arctic Rhizobium strain having an earlier and higher symbiotic nitrogen fixation efficiency than the wild type. PMID- 24221112 TI - The use of constrained selection indexes in breeding for economic merit. AB - Various methods exist for the derivation of restricted and/or desired gains selection indexes, and their use in applied breeding has been advocated. It is shown that there exists a set of implied linear economic weights for all constrained indexes and their derivation is given. Where economic weights are linear and known, a standard selection index is, by definition, optimal and thus a constrained index will usually be suboptimal. It is argued that economic weights can always be estimated and that the effects of uncertain weights can be examined by sensitivity analysis. If economic weights are nonlinear, use of the first order (linear) economic weights or a derived linear index, using previously described methods, will give very close to optimum economic selection responses. Examples from the literature indicate that severe losses of potential economic gain can possibly occur through use of a constrained index. It is concluded that constrained indexes should be avoided for economic genetic selection. PMID- 24221113 TI - Milling energy requirement of the aneuploid stocks of common wheat, including alien addition lines. AB - Aneuploid stocks, which included Triticum aestivum/alien, disomic, chromosome addition lines, wheat/alien, ditelosomic, chromosome addition lines, and the available aneuploids of "Chinese Spring" wheat, were used to locate genes that influence milling energy requirement (ME). Genes that affected ME were found on all seven homoeologous chromosome groups. The addition of complete wheat chromosomes 1B, 1D, 2A, 2D, 5B, 6B, 7B and 7D increased ME. Positive effects were also found in specific chromosome arms: 1BS, 2DS, 5AS, 5BS and 6BL. Wheat chromosome 3B conditioned low ME and the gene(s) responsible was located on the short arm. Other negative effects were attributed to wheat chromosome arms 4BL, 4DL, 5DS and 6DS. Alien chromosome additions that conferred high ME included 2H, 5H, 6H and 7H of barley, Hordeum vulgare and 2R, 2Ralpha, 4R, 4RL, 6R, 6RL and 7RL of rye, Secale cereale. Those that conferred a low ME included 1H (ch) of H. chilense, and 6u and 7u of Aegilops umbellulata, 5R and 5RS of S. cereale and 5R (m) and 5R (m)S of S. montanum. Although the control of ME is polygenic, there is a major effect of genes located on the short arms of homoeologous group 5 chromosomes. PMID- 24221114 TI - Resistance of maize to Meloidogyne arenaria and Meloidogyne javanica. AB - A diallel cross of eight maize, Zea mays L., inbred lines was analyzed for reaction to two species of root-knot nematodes, Meloidogyne arenaria (Neal) Chitwood and M. javanica (Treub) Chitwood. Egg production following inoculation of F1 hybrid seedlings with nematode eggs was determined in a greenhouse experiment. Data were analyzed using Griffing's Method 4, Model I. General combining ability was a significant source of variation in egg production of both M. arenaria and M. javanica; specific combining ability was not a significant source of variation for either. The correlation between egg production of the two nematode species on the 28 F1 hybrids was highly significant. Hybrids with Mp313 or SC213 as one parent were the most resistant to both species. This indicates that germ plasm is available for developing inbred lines and hybrids with resistance to both M. arenaria race 2 and M. javanica. PMID- 24221115 TI - Gene delivery into cultured plant cells by DNA-coated gold particles accelerated by a pneumatic particle gun. AB - Transient expression of the beta-glucuronidase (GUS) gene in suspension-cultured cells of tobacco was obtained after gene delivery with a pneumatic particle gun device driven by compressed air. Both the pneumatic pressure used to accelerate the particles as well as the distance between the point of release of the particles from the device and the location of the target cells could be varied. Efficiency of gene delivery was tested by accelerating pressure from 63 to 200 kg/cm(2) and distances from 5 to 15 cm. At 150 kg/cm(2) and 10cm, 618+/-49 blue spots of GUS-expressing cells were evenly distributed over the surface of the cell layer (3.5 cm diameter). The frequency of transient gene expression was estimated to be more than 1.2*10(-3), which is comparable to, or even higher than, that obtained by the gunpowder-driven device. PMID- 24221116 TI - Somaclonal variation in tomato: effect of explant source and a comparison with chemical mutagenesis. AB - Plants were regenerated from leaf, cotyledon, and hypocotyl explants of tomato cv Moneymaker. Various phenotypic alterations were observed among regenerated plants (R1), but were not transmitted to the progenies, except for ploidy variation. Variation in ploidy level, mainly tetraploidy, occurred in R1 plants and their R2 progenies, and the frequency of polyploid plants depended on the explant source. More than 50% of the regenerants derived from hypocotyl explants were found to be polyploid. A correlation was observed between the percentage of polyploid cells present in the explant material in vivo and the frequency of polyploid plants. Several monogenic mutations were recovered in the R2, four of which were shown to be allelic to known, recessive, single-gene mutants. No significant effect of explant source or duration of tissue culture period on mutant frequency or spectrum was found. For several mutant types that could be scored unambiguously, somaclonal variation was compared to variation induced by treatment of seeds with ethyl methane sulphonate (EMS). The results showed that the mutant frequencies were higher after EMS treatment than those generated through tissue culture. With respect to the mutant spectrum, no clear differences were observed between the spectra obtained after EMS treatment and those after tissue culture. However, tissue culture gave rise to polyploid plants, whereas no ploidy variants occurred after EMS treatment. PMID- 24221117 TI - Assessment of the degree and the type of restriction fragment length polymorphism in barley (Hordeum vulgare). AB - In order to determine the extent of polymorphism in barley (Hordeum vulgare), DNA from 48 varieties was analyzed with 23 genomic, single-copy probes, distributed across all seven chromosomes. Upon hybridization to wheat-barley addition lines, the probes showed different degrees of homology compared to the wheat genome. Polymorphisms were detected in the barley genome at a frequency of 43% after digestion with EcoRI, BamHI, and HindIII. Subgroups of spring and winter barley and of two- and six-rowed types showed less diversity which, in most cases, was due to shifts in allelic frequencies. One probe (MWG1H504) hybridized to an EcoRI restriction fragment exclusively observed in winter barley. A comparison of six different restriction enzymes revealed clear differences with regard to their efficiency in detecting polymorphisms. The respective frequencies were between 13% (HindIII) and 37% (EcoRV). A significant correlation between the efficiency of a restriction enzyme and the mean fragment size detected by the different probes identified insertion/deletion events as the major factor causing polymorphism in barley. PMID- 24221118 TI - Similarities among a group of elite maize inbreds as measured by pedigree, F1 grain yield, grain yield, heterosis, and RFLPs. AB - Genetic distances were calculated among 37 inbred lines representing a wide range of related and unrelated elite Corn Belt germ plasm of maize (Zea Mays L.), using 257 probe restriction enzyme combinations. Genetic distances based on RFLP data were highly correlated with coefficients of parentage among pairs of lines. The RFLP-based distance had a higher correlation with single-cross grain yield performance and grain yield heterosis than any of the other measures of similarity we calculated using these same lines. The coefficients of determination (r (2)) from regressing the coefficient of parentage, grain yield, and grain yield heterosis on Nei's measure of genetic similarity based on RFLP data were 0.81, 0.87 and 0.77, respectively. A cluster diagram based upon the RFLP data grouped the lines into families consistent with the breeding history and heterotic response of these lines. We believe that measures of similarity calculated from RFLP data, coupled with pedigree knowledge and using molecular markers to locate quantitative trait loci (QTL), could allow maize breeders to predict combinations of lines that result in high-yielding, single-cross hybrids. PMID- 24221119 TI - Modification of amino acid composition of endosperm proteins from in-vitro selected high lysine mutants in rice. AB - Endosperm protein mutants in rice may be recovered by biochemical selections with inhibitory levels of lysine and threonine. Among the phenotypes recovered from in vitro selections are lines with increased protein and percent lysine in the protein. This work was designed to identify changes in proteins of rice mutants and to further our understanding of the mechanisms of lysine plus threonine selections in rice. Among the most obvious amino acid changes in mutants was a higher lysine level in all protein solubility fractions and a decrease in tyrosine. Methionine and glutamate are reduced in some protein fractions. However, methionine is significantly higher in the mutant than the control in the glutelin fraction. Several other aspartate pathway amino acids are higher in the mutant than the unselected controls. Separation of proteins in SDS-PAGE gels showed shifts in the protein profiles in the mutants, including a decrease in the major 30 kDa low lysine globulin component, and an increase in several high molecular-weight components, approximately 60-100 kDa. Increases in the lysine content of proteins of different solubility classes and different proteins within classes are detailed. PMID- 24221120 TI - Genetic and environmental factors in the resistance of Drosophila subobscura adults to high temperature shock : 2. Modification of heat resistance by indirect selection. AB - We have carried out two equivalent selection experiments to increase and decrease heat shock resistance of Drosophila subobscura adults, using an indirect selection method that avoids excessive consanguinity. Heat shock was 33+/-0.5 degrees C at saturation humidity. Control lines showed a rapid change of the physiological trait as a consequence of laboratory culture conditions, expressed as a decrease both in heat shock resistance and in the initial population variability for heat shock resistance. Thus, this reduction of variability seems to consist in the loss of those combinations of genes that confer high resistance to heat shock. After eight generations of selection, the selected lines were differentiated from their respective control lines, and the selection response obtained was similar in "resistant" and "sensitive" lines. Differences in survival of progeny of reciprocal crosses between selected lines suggest that inheritance of heat resistance may depend in part on the origin of egg cytoplasm. PMID- 24221121 TI - The isolation and characterization of gibberellin-deficient mutants in tomato. AB - In tomato, nine independent EMS-induced mutants representing recessive mutations at three different loci (gib-1, gib-2, and gib-3) were isolated. Six of these have an almost absolute gibberellin requirement for seed germination and elongation growth. In addition, the leaves are darker green, smaller, and changed in structure as compared to wild type. The three other mutants, which germinate without GA, are allelic to specific, nongerminating mutants and have less severe mutant characteristics. The respective loci are situated on three different chromosomes. The genes identified by these mutants control steps in gibberellin biosynthesis, as endogenous gibberellins are strongly reduced. PMID- 24221122 TI - Prognostic value of arterial blood gas disturbances for in-hospital mortality in pediatric patients with severe traumatic brain injury. AB - BACKGROUND: The aim of this study was to evaluate the changes of arterial blood gas as a secondary insult in children and young adults suffering from severe traumatic brain injury, and to assess the correlation, if any, with their in hospital mortality. METHOD: In this cross-sectional study, the medical data of all children and adolescents with severe head trauma admitted to the Rasht Poursina Hospital were reviewed between April 2006 and September 2011. Data including age, gender, GCS upon admission, arrival and daily ABG values for the first 3 days, results of brain CT scan, as well as in-hospital mortality rate were collected. A logistic regression model was used to determine the association between acid-base disturbance and in-hospital mortality after adjustment for potential confounding factors. RESULT: Of the 108 patients, 75% were male and 25% were female; and 31.5% of them died in the hospital. Univariate analysis showed a significantly higher risk of mortality in patients who developed mixed metabolic acidosis plus respiratory acidosis on their admission day (OR = 3.94, p = 0.012). Multiple logistic regression analysis demonstrated that mixed metabolic acidosis plus respiratory acidosis (OR = 3.81, 95% CI = 1.18-12.27, p-value = 0.025) and GCS (OR = 0.457, 95 % CI = 0.31-0.65, p-value < 0.001) were two significant predictors of mortality, regardless of other confounding variables. CONCLUSION: The results of present study show that, in pediatric patients with severe head injuries, initial mixed metabolic acidosis plus respiratory acidosis and GCS are significant predictors of mortality, but other factors after adjustment for potential confounding factors had no prognostic effect. PMID- 24221123 TI - Concentrations of heavy metals in oysters from the coastline of Northern Territory, Australia. AB - The concentrations of five metals in oysters from ten locations along the Northern Territory coastline were determined during the dry season of 1989. The measured concentrations of iron, cadmium, zinc, manganese and copper in oysers were 11.6-274, 0.17-9.1, 4.79-735, 0.25-69.85 and nd-70.2 ug g(-1) wet weight. The level of cadmium exceeded the National Health and Medical Research Council (NHMRC) recommended limit at five sites. The largest fluctuation occurred in zinc and cadmium while the other metals displayed much less variation. PMID- 24221124 TI - Comparison of a matrix solid phase dispersion and a classical extraction method for the determination of chlorinated pesticides in fish muscle. AB - A new multiresidue extraction technique was used to determine incurred chlorinated hydrocarbon pesticide residues in various fish species sampled at 2 locations along the Tensas River in Louisiana. Residue levels of total DDT (combined DDT, DDE, and DDD levels) in fish muscle fillets from paired samples ranged from 0.2 to 3.9 ppm on a wet weight basis. These findings were compared to those of another laboratory that used a different protocol to isolate the residues from the fish muscle fillets. This latter protocol typifies the more complicated, time-consuming protocols used by governmental agencies for screening purposes. Results demonstrated that the new extraction technique reduced analysis time, solvent waste, and cost per sample without affecting the quality of residue detection and measurement. PMID- 24221125 TI - Lake Ontario sediments in monitoring pollution. AB - An investigation was carried out to select locations for long-term monitoring of inputs of contaminants into Lake Ontario using fine-grained bottom sediments as an historical record of pollution. The sediment sampling program was designed to determine sediment heterogeneity in the western, central and eastern depositional basins of the lake. Surficial sediments and sediment cores were collected in each basin to obtain information on horizontal distribution and concentration profiles of major and trace elements in the sediments (Si, Al, Ca, Mg, Fe, Na, K, Ti, Mn, P, As, Co, Cu, Cr, Ni, Pb and Zn). The results of the investigation indicated that fine-grained sediments in three Lake Ontario depositional basins are homogeneous to a high degree, and that only a few sediment cores need to be collected within each basin for the long-term monitoring of inputs of contaminants to the lake. PMID- 24221126 TI - In vivo effects of trivalent and hexavalent chromium on renal and hepatic atpases of a freshwater teleost Anabas scandens. AB - The in vivo toxic effect of trivalent and hexavalent chromium (25 mg/L) on the renal and hepatic tissue ATPases of an edible teleost Anabas scandens was studied. In an exposure span of 30 days Na(+)-K(+) ATPase activity exhibited a progressive inhibition in the kidney, but marked inhibition in Na(+)-K(+) ATPase activity was observed in the liver. Mg(2+) ATPase activity, however, exhibited an elevation on early exposures, with a later inhibition. PMID- 24221127 TI - Biological monitoring of atmospheric trace metal deposition in North-Eastern Nigeria. AB - The epiphytic moss Polytrichum juniperinum and the tree bark of Azardirachta indica were used to determine the atmospheric Cd, Cu, Pb, Mn, Fe, Ni and Zn levels in the North-East region of Nigeria. A good correlation exists between levels in the moss and the tree barks. The Pb, Zn and Fe levels in both sample types were higher than other metals in most sites. There was no significant difference in the levels of Cd, Cu, Ni and Mn recorded for inhabited and forest sites. The area derives its atmospheric metal contamination from vehicular, urban, industrial and agricultural sources. PMID- 24221128 TI - Depositional profiles and relationships between organotin compounds in freshwater and estuarine sediment cores. AB - A range of organotin compounds including tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) were measured in sediment cores collected from contaminated freshwater and estuarine sites in Essex and Suffolk, U.K. Butyltin compounds were found in significant quantities at depths of up to 60 cm within the sediments of marina and boatyard complexes with TBT concentrations ranging from <3 ng g(-1) (the detection limit) to >3000 ng g(-1). In general sediment TBT concentrations decreased with depth, but maximum enrichment tended to occur just below the surface. It was evident from these core profiles that the accumulation of organotins in surface deposits was on the decline and coincided approximately, with the implementation in 1987 of the UK retail ban on the sale of TBT based antifouling paints for application on vessels <25 m in length. The degradation rate for TBT in sediments was found to exhibit first order kinetics with half lives ranging from 0.9-5.2 years between different sites. Estimated degradation rates have also been determined for DBT and MBT. These ranged from 1.5-3.0 years for DBT and 1.8-3.7 years for MBT. PMID- 24221129 TI - Evolutionary consequences for ecological risk assessment and management. AB - The human health risk assessment (HRA) paradigm is being used as a basis for developing ecological risk assessment (ERA). The modification of the HRA paradigm to ERA will be most useful in an ecotoxicological sense, to assess the effect of hazards to single indicator species and populations, rather than to ecosystems. However, even for single species and population assessments, there are major differences in HRA and ERA. One such difference derives from the HRA tenet that human impairment at any age is important, and that each individual is important. For ERA, individuals are less important, and it is the population and its survival and interactions that are of concern. One exception is in the case of endangered species where every individual is critical because of its potential impact on survival and genetic diversity of the species. We suggest that ERA must take into account the relative reproductive value of the potentially impacted individuals in assessing hazards. This will involve adding additional steps to evaluate the value of the individual to current population levels, assessing reproductive value, and assessing recovery potential. Although ecologists recognize the importance of these factors, we suggest that they should be integral parts of ecological risk assessment. PMID- 24221131 TI - Forest damage assessments in Austria. AB - Different types of assessments of forest damage are conducted in Austria. Faced with forest dieback reports, a needle and leaf sampling programme and a terrestrial crown assessment have been started after 1983, in addition to the forest inventory. In order to obtain more comprehensive and detailed information for the analysis of cause-effect relationships, as many investigations concerning forest health status as possible were concentrated on permanent plots out of the grid of the Austrian National Forest Inventory. This new, long-term project, started in 1987, was called the Forest Damage Monitoring System. An overview of the investigations and assessments, as they have been conducted by the end of 1991, is given in this paper. PMID- 24221130 TI - Effective monitoring of pollution by toxic trace elements in waters, sediment and biota of the Derwent River Estuary, Tasmania, through long-term retention of analytical facilities. AB - This study considers the effectiveness of the monitoring of toxic trace elements in various media from a polluted river estuary over a period of 15 years, using the same analytical techniques, facilities and, in some cases, the same operators. It shows that reliable comparisons can be made for monitoring waters, sediment and biota from the Derwent River Estuary between 1975 data and that from 1990. Rigorous studies were undertaken before and during 1975 to ensure that reliable data was achieved at that time. Such studies are reviewed and included the evaluation of digestion techniques for a range of heavy metals, specific attention to the reliability of mercury determination in sediments between laboratories, a comparison of direct calibration and standard addition techniques for metals in seawater, recoveries of an organomercury compound from fish, and sources of error arising from sample preparation of biota for subsequent metal analysis. Comparative results for standard reference materials in both 1975 and 1990 show good agreement and are considered reliable except for lead at low concentrations. The long-term retention of the analytical facilities permits a direct comparison of data from 2 monitoring programmes over the space of 15 years. PMID- 24221132 TI - Heavy metals and selenium in feathers of three shorebird species from Delaware bay. AB - Concentrations of lead, cadmium, mercury, selenium, chromium and manganese were examined in breast feathers of shorebirds migrating north through Cape May, New Jersey in 1991 and 1992. Although we predicted that metal levels would be positively correlated with weight, this was only true for mercury in red knots (Calidris canutus). Selenium was negatively correlated with weight in red knots. No other significant correlation of metal concentrations with weight were found. Lead and mercury were highest in sanderlings (C. alba). Selenium and manganese were highest in red knots, while chromium and cadmium levels were highest in semipalmated sandpipers (C. pusilus). For 1991, interspecific metals differences were significant for all metals except lead. For semipalmated sandpipers, cadmium and chromium concentrations were significantly higher in 1991 while managese concentrations were significantly higher in 1992. PMID- 24221134 TI - Anti-Candida activity of 1-18 fragment of the frog skin peptide esculentin-1b: in vitro and in vivo studies in a Caenorhabditis elegans infection model. AB - Candida albicans represents one of the most prevalent species causing life threatening fungal infections. Current treatments to defeat Candida albicans have become quite difficult, due to their toxic side effects and the emergence of resistant strains. Antimicrobial peptides (AMPs) are fascinating molecules with a potential role as novel anti-infective agents. However, only a few studies have been performed on their efficacy towards the most virulent hyphal phenotype of this pathogen. The purpose of this work is to evaluate the anti-Candida activity of the N-terminal 1-18 fragment of the frog skin AMP esculentin-1b, Esc(1-18), under both in vitro and in vivo conditions using Caenorhabditis elegans as a simple host model for microbial infections. Our results demonstrate that Esc(1 18) caused a rapid reduction in the number of viable yeast cells and killing of the hyphal population. Esc(1-18) revealed a membrane perturbing effect which is likely the basis of its mode of action. To the best of our knowledge, this is the first report showing the ability of a frog skin AMP-derived peptide (1) to kill both growing stages of Candida; (2) to promote survival of Candida-infected living organisms and (3) to inhibit transition of these fungal cells from the roundish yeast shape to the more dangerous hyphal form at sub-inhibitory concentrations. PMID- 24221133 TI - Mechanisms of cellular invasion by intracellular parasites. AB - Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality. PMID- 24221137 TI - C-reactive protein (CRP) responses in neonates with hypoxic ischaemic encephalopathy. PMID- 24221138 TI - Comparison of different pseudotumor grading systems in a single cohort of metal on-metal hip arthroplasty patients. AB - OBJECTIVE: Follow-up of pseudotumors observed with metal-artefact reducing sequence (MARS)-magnetic resonance imaging (MRI) following metal-on-metal total hip arthroplasty (MoMTHA) depends on how severe these pseudotumors are graded. Several pseudotumor grading systems for MARS-MRI have emerged but little is known of their validity. We studied the intra- and interobserver reliability of three different pseudotumor grading systems in a single cohort of MoMTHA. PATIENTS AND METHODS: Two experienced musculoskeletal radiologists independently used three different pseudotumor grading systems for classifying MARS-MRI results of the same cohort of 42 MoMTHA patients (49 hips, mean follow-up 5.2 years). Intraobserver and interobserver reliability for each grading system was measured using Cohen's kappa (kappa). Variance in pseudotumor severity grading between systems was analyzed. RESULTS: Intraobserver reliability on grading pseudotumor severity with the Anderson, Matthies, and Hauptfleisch grading system scored 0.47, 0.10, and 0.35 (observer 1), and 0.75, 0.38, and 0.42 (observer 2), respectively. Interobserver reliability scores for pseudotumor severity were 0.58, 0.23, and 0.34, respectively. CONCLUSIONS: Intraobserver reliability for grading pseudotumor severity on MARS-MRI ranged from poor to good, dependent on observer and grading system used. Interobserver reliability scored best with the Anderson system. A more succinct pseudotumor severity grading system is needed for clinical use. PMID- 24221135 TI - Challenging the future of siRNA therapeutics against cancer: the crucial role of nanotechnology. AB - The identification of numerous deregulated signaling pathways on cancer cells and supportive stromal cells has revealed several molecular targets whose downregulation can elicit significant benefits for cancer treatment. In this respect, gene downregulation can be efficiently achieved by exploiting the RNA interference mechanism, particularly by the delivery of chemical synthesized small-interfering RNAs (siRNAs), which have the ability to mediate, in a specific manner, the degradation of any mRNA with complementary nucleotide sequence. However, several concerns regarding off-target effects and immune stimulation have been raised. Depending on their sequence, siRNAs can trigger an innate immune response, which might mediate undesirable side effects that ultimately compromise their clinical utility. This is a very relevant effect that will be discussed in the present manuscript. Moreover, the major drawback in the translation of siRNAs into the clinical practice is undoubtedly their inability to accumulate in tumor sites, particularly in organs other than the liver. In fact, upon systemic administration, owing to siRNAs physico-chemical features, they are rapidly cleared from the blood stream. Therefore, the development of a proper drug delivery system is of utmost importance. In this review, some of the latest advances on different nanotechnological platforms for siRNA delivery under clinical evaluation will be discussed. Along with this, targeting approaches towards cancer and/or endothelial cells will also be addressed, as these are some of the most promising strategies to enhance specific tumor accumulation while avoiding healthy tissues. Finally, clinical information on ongoing studies in patients with advanced solid tumors will be also provided. PMID- 24221140 TI - Dextran/Albumin hydrogel sealant for Dacron(R) vascular prosthesis. AB - In this paper, the authors describe a novel type of hydrogel coating prepared from the copolymer of human serum albumin and oxidized dextran. The material was designed as a hydrogel sealant for polyester (Dacron(r))-based vascular grafts. Dextran was chosen as a coating material due to its anti-thrombogenic properties. Prepared hydrogels were compared with similar, already known biomaterial made from gelatine with the same cross-linking agent. Obtained hydrogels, prepared from various ratios of oxidized dextran/albumin or oxidized dextran/gelatine, showed different cross-linking densities, which caused differences in swelling, degradation rate and mechanical properties. Permeability tests confirmed the complete tightness of the hydrogel-modified prosthesis. Results showed that application of the hydrogel coating provided leakage-free prosthesis and eliminated the need of pre-clotting. PMID- 24221139 TI - The effects of weight-bearing conditions on patellofemoral indices in individuals without and with patellofemoral pain syndrome. AB - OBJECTIVE: The purpose of this study is to evaluate differences between the patellofemoral joint indices after supine, non-weight-bearing and standing position, and weight-bearing Merchant view radiographs in individuals without and with patellofemoral pain syndrome (PFPS). MATERIALS AND METHODS: Radiographs of 44 knees without PFPS and 51 knees with PFPS were retrospectively evaluated. In both positions, the non-weight-bearing and weight-bearing Merchant views, patellar indices such as patellar tilt angle, lateral patellofemoral angle, lateral subluxation distance, lateral patellar displacement, and congruence angle were measured, respectively. The differences between the patellofemoral joint indices in knees with and without PFPS were analyzed using univariate and multivariate regression analysis, in regards to correlation factors. RESULTS: The patellar tilt angle (p = 0.0002), lateral subluxation distance (p = 0.038), lateral patellar displacement (p = 0.0004), and congruence angle (p < 0.0001) on the weight-bearing Merchant view was significantly decreased in normal knees without PFPS. In pathologic knees with PFPS, the patellar tilt angle (p < 0.0001), lateral subluxation distance (p < 0.0001), lateral patella displacement (p < 0.0001), and congruence angle (p < 0.0001) on weight-bearing Merchant view was also significantly decreased. The difference between the patellofemoral indices was significantly more in knees specifically with PFPS (p < 0.05). CONCLUSIONS: These results suggest that patellofemoral indices measured during non-weight-bearing supine position do not sufficiently represent the patellofemoral kinematics during normal weight-bearing activities. We conclude that this study establishes the clinical significance and relevance of assessing the patellofemoral kinematics by weight-bearing, standing Merchant view radiographs, when evaluating patients with patellofemoral problems. PMID- 24221141 TI - Pure culture growth of ectomycorrhizal fungi on inorganic nitrogen sources. AB - Four ectomycorrhizal fungi were tested for their ability to grow (i.e., mycelial mat radial extension and fungal biomass) on nutrient media either supplemented with ammonium-nitrogen or nitrate-nitrogen or in the absence of an inorganic nitrogen source.Pisolithus tinctorius, Cenococcum geophilum andThelephora terrestris exhibited greater growth on ammonium-nitrogen.Suillus granulatus grew better on the nitrate-nitrogen nutrient medium. Regardless of inorganic nitrogen form preference (i.e., ammonium-nitrogen or nitrate-nitrogen), all 4 species showed some growth on each of the 3 nutrient media. Growth rate maxima varied by fungal species as well as by inorganic nitrogen source. Maximum growth rate forT. terrestris exceeded rates exhibited by the other 3 fungi by 2-5 times. PMID- 24221142 TI - Fungal populations in podzolic soil experimentally acidified to simulate acid rain. AB - The effect of experimental acidification on the soil microfungal community was studied in the humus layer of a coniferous forest in northern Sweden. The study was made 4 years after the last application of sulfuric acid. Fungal species composition was altered by treatments of 100 and 150 kg sulfuric acid ha(-1) each year for 6 years, yet no differences were found between the control treatment and an application of 50 kg ha(-1). The abundance ofPenicillium spinulosum andOidiodendron cf.echinulatum II increased with increasing rates of acid application, whereas only small changes were found for other isolated fungal taxa. Soil respiration rate and fluorescein diacetate (FDA)-active fungal biomass were significantly different from the control treatment at all 3 levels of acidification. PMID- 24221136 TI - Transcriptional control of mammalian pancreas organogenesis. AB - The field of pancreas development has markedly expanded over the last decade, significantly advancing our understanding of the molecular mechanisms that control pancreas organogenesis. This growth has been fueled, in part, by the need to generate new therapeutic approaches for the treatment of diabetes. The creation of sophisticated genetic tools in mice has been instrumental in this progress. Genetic manipulation involving activation or inactivation of genes within specific cell types has allowed the identification of many transcription factors (TFs) that play critical roles in the organogenesis of the pancreas. Interestingly, many of these TFs act at multiple stages of pancreatic development, and adult organ function or repair. Interaction with other TFs, extrinsic signals, and epigenetic regulation are among the mechanisms by which TFs may play context-dependent roles during pancreas organogenesis. Many of the pancreatic TFs directly regulate each other and their own expression. These combinatorial interactions generate very specific gene regulatory networks that can define the different cell lineages and types in the developing pancreas. Here, we review recent progress made in understanding the role of pancreatic TFs in mouse pancreas formation. We also summarize our current knowledge of human pancreas development and discuss developmental pancreatic TFs that have been associated with human pancreatic diseases. PMID- 24221143 TI - Can bacteria outcompete phytoplankton for phosphorus? a chemostat test. AB - Although the bacterioplankton of lakes are usually considered primarily in terms of mineralization processes, recent studies suggest that they may also strongly compete for phosphorus with the phytoplankton. In the present study, we have tested in chemostat culture, and found support for the hypotheses that (1) a freshwater bacterium (Pseudomonas paucimobilis), whose carbon source is excretion from a phosphorus-limited alga (Synedra ulna var.danica), can outcompete that alga for phosphorus (P) under widely varied P supply rates; (2) exogenously supplied organic carbon positively influences bacterial biomass and negatively influences algal biomass; (3) the ratio of bacterial to algal phosphorus uptake in short-term(32)P orthophosphate uptake experiments is an accurate predictor of their relative long-term phosphorus assimilation (i.e., growth) in mixed culture. PMID- 24221144 TI - Bacterial adaptation to low-nutrient conditions as studied with algal extracellular products. AB - Kinetic analyses indicate that members of natural bacterial populations from 2 marine environments near Woods Hole, MA, possess enzyme-mediated transport systems which permit utilization of(14)C-labeled extracellular organic C ((14)C EOC) prepared from the algae,Skeletonema costatum, Thalassiosira pseudonana, andDunaliella tertiolecta, and supplied over a concentration range of 15 150MUC.liter(-1). It is shown that previous exposure of the bacteria to the EOC from these algae cannot explain the linear kinetic patterns obtained. Therefore, the ability to utilize algal EOC at low concentrations is a general feature of metabolically active bacterial populations. Further, as the native bacteria do not restrict this ability to a specific EOC pool, the results are consistent with the hypothesis that bacteria adapted to low nutrient environments possess uptake systems of high substrate affinity and low substrate specificity. Elevation of substrate levels with as little as 10 mg.1(-1) peptone is shown to favor development of a bacterial population that lacks these adaptations. Standard enrichment techniques typically result in the isolation of bacteria that are poor models for evaluating the ecology of native microbiota. PMID- 24221145 TI - Sea ice microbial communities. III. Seasonal abundance of microalgae and associated bacteria, Mcmurdo Sound, Antarctica. AB - Numbers of bacteria in annual sea ice increased directly with numbers of algae during the 1981 spring ice diatom bloom in McMurdo Sound, Antarctica. Algae and bacteria in a control site grew at rates of 0.10 and 0.05 day(-1), respectively, whereas in an experimentally darkened area neither increased after six weeks. Epiphytic bacteria grew at a rate twice that of the nonattached bacteria and were significantly larger, contributing approximately 30% of the total bacterial biomass after October. The microalgal assemblage was dominated by two species of pennate diatoms, anAmphiprora sp. andNitzschia stellata. Greater than 65% of epiphytic bacteria were associated withAmphiprora sp. after October.N. stellata, however, remained largely uncolonized throughout the study. We hypothesize that microalgae stimulate bacterial growth in sea ice, possibly by providing the bacteria with organic substrates. PMID- 24221146 TI - Distribution and activity of bacteria in the headwaters of the Rhode River Estuary, Maryland, USA. AB - A transect along the axis of the headwaters of a tidal estuary was sampled for microbial, nutrient, and physical parameters. Chlorophylla averaged 42MUg 1(-1) and phytoplankton comprised an estimated 80% of the total microbial biomass as determined by adenosine triphosphate (ATP). Bacterial concentrations ranged from 0.3-53.9*10(6) cells ml(-1) and comprised about 4% of the total living microbial biomass. Bacterial production, determined by(3)H-methyl-thymidine incorporation was about 0.05-2.09* 10(9) cells 1(-1) h(-1), with specific growth rates of 0.26 1.69 d(-1). Most bacterial production was retained on 0.2MUm pore size filters, but passed through 1.0MUm filters. Significant positive correlations were found between all biomass measures and most nutrient measures with the exception of dissolved inorganic nitrogen nutrients where correlations were negative. Seasonal variability was evident in all parameters and variability among the stations was evident in most. The results suggest that bacterial production requires a significant carbon input, likely derived from autotrophic production, and that microbial trophic interactions are important. PMID- 24221147 TI - Interactions of carbaryl with estuarine bacterial communities. AB - The addition of carbaryl (100MUg/ml) to a model estuarine ecosystem did not affect the number of bacteria in the sediment, but reduced the diversity (as measured by the rarefaction technique) of the microbial community as compared with a control model ecosystem. Two carbaryltolerant strains of bacteria were isolated from the carbaryl-treated system, but none were isolated from the control system. Bacterial growth and filter paper decomposition in mixed cultures was prevented by 100MUg/ml carbaryl, but this amount had no effect on the extracellular cellulase of an estuarine isolate. Increasing the amount of organic matter in the medium attenuated the toxicity of carbaryl to pure cultures of an estuarine isolate. The addition of 1, 10, or 100MUg/ml carbaryl to field plots had no effect on bacterial numbers, diversity, or filter paper decomposition. The amount of carbaryl in sediments exposed to 100MUg/ml fell below the limit of detection by thin-layer chromatography within 12 hours. In sterile and nonsterile model systems, carbaryl rapidly adsorbed to sediment, and hydrolyzed to 1 naphthol in both sediment and water. Although carbaryl may be toxic to bacteria under some conditions, the amounts that might enter and persist in an estuary are insufficient to have a significant impact on the sediment microbial community. PMID- 24221148 TI - Vibrio species associated with mortality of sharks held in captivity. AB - Two urease-positiveVibrio spp. were isolated from a brown shark (Carcharhinus plumbeus) that died in captivity at a national aquarium. Morphological, biochemical, and molecular genetic studies revealed one of the isolates to beV. damsela; the other isolate was unique and has been classified asV. carchariae sp. nov. BothV. damsela andV. carchariae were found to be virulent for spiny dogfish (Squalus acanthias), causing death in less than 18 hours after intraperitoneal injection of ca. 4*10(6) cells.V. damsela was strongly cytotoxic for Y1 adrenal cell monolayers;V. carchariae exhibited weak cytotoxicity for Y1 cells.V. damsela contained cryptic plasmids and both isolates were urease positive.V. carchariae was able to utilize urea as sole source of carbon and nitrogen. PMID- 24221149 TI - Application of FAME (fatty acid methyl ester) analysis in the numerical taxonomic determination of bacterial guild structure. AB - Comparative numerical taxonomic analyses, using fatty acid methyl ester (FAME) profiles and phenetic characteristics, were conducted to examine bacterial guild structure in freshwater sediments. Both approaches were used to examine a subset of 60 OTUs obtained from a previously well characterized microbial community in sediments of a shallow fast flowing stream. For both classifications, greater than 80% of the OTUs were recovered in 11 and 12 major groups for FAME and phenetics approaches. However, there was not complete correspondence for the groupings of the 2 classifications, with most FAME groups being distributed among the phenetic groups and 2 phenetic groups not providing usable characteristics for FAME analysis. The results did demonstrate significant taxonomic variation in bacteria capable of occupying the same or a similar fundamental niche. PMID- 24221150 TI - A bird's eye view of home. PMID- 24221151 TI - Characterization of a gametoclonal variant controlling virus resistance in tobacco. AB - Potato virus Y (PVY), susceptible tobacco (Nicotiana tabacum L.) cultivar, McNair 944, was subjected to in vitro anther culture to determine if genetic variability for virus resistance could be induced among resulting haploids. Five hundred and forty-five haploids were produced and inoculated with a highly necrotic strain (NN) of PVY. One haploid plant survived, even though it was infected with the virus. Selfed progenies of a chromosome-doubled plant of this variant, designated NC 602, proved to be highly resistant to the necrotic effects of the virus. An investigation into the genetic nature of this variant showed the resistance mechanism to be controlled by a single gene exhibiting incomplete dominance. Cytoplasmic and maternal effects were not involved in the disease resistance reaction. The variant was challenged with ten additional strains of PVY from an international collection, and it proved to be resistant to three (VAM-B, MM, and Spanish) strains. NC 602 was evaluated for five agronomic traits and concentrations of total alkaloids as nicotine and reducing sugars in cured leaf. The gametoclonal variant differed from McNair 944 only for cured leaf yield, where an 18.4% reduction was measured. PMID- 24221152 TI - Triploidy induction in Nile tilapia, Oreochromis niloticus L. using pressure, heat and cold shocks. AB - The results of a study aimed at the identification of treatment optima for triploidy induction in recently fertilised Oreochromis niloticus L. eggs by altering the intensity, duration and timing of application of pressure, heat and cold shocks are reported. Preliminary, but not directly comparable, trials suggested the following treatments to be close to the individual agent optima. Pressure: 8,000 psi 2-min duration applied 9 min after fertilisation (a.f.); heat: 41 degrees C, 3.5-min duration applied 5 min a.f., cold: 9 degrees C, 30 min duration applied 7 min a.f. In a directly comparable trial in which the eggs of eight different females were separately exposed to the optimum shocks listed above, individual triploid yields were more variable following cold shocks and mean triploid yields were, therefore, higher following pressure and heat shock. These and other results obtained are presented and the light they shed on the timing of the second meiotic division in this species is discussed. PMID- 24221153 TI - Chloroplast DNA evolution in potato (Solanum tuberosum L.). AB - A deletion specific to chloroplast (ct) DNA of potato (Solanum tuberosum ssp. tuberosum) was determined by comparative sequence analysis. The deletion was 241 bp in size, and was not flanked by direct repeats. Five small, open reading frames were found in the corresponding regions of ctDNAs from wild potato (S. tuberosum ssp. andigena) and tomato (Lycopersicon esculentum). Comparison of the sequences of 1.35-kbp HaeIII ctDNA fragments from potato, tomato, and tobacco (Nicotiana tabacum) revealed the following: the locations of the 5' ends of both rubisco large subunit (rbcL) and ATPase beta subunit (atpbeta) mRNAs were probably the same as those of spinach (Spinacia oleracea); the promoter regions of the two genes were highly conserved among the four species; and the 5' untranslated regions diverged at high rates. A phylogenetic tree for the three potato cultivars, one tomato cultivar, and one tobacco cultivar has been constructed by the maximum parsimony method from DNA sequence data, demonstrating that the rate of nucleotide substitution in potato ctDNA is much slower than that in tomato ctDNA. This fact might be due to the differences in the method of propagation between the two crops. PMID- 24221154 TI - Quantitative cytology of the alfalfa generative cell and its relation to male plastid inheritance patterns in three genotypes. AB - Studies utilizing restriction analysis of plastid DNA, as well as those employing chlorophyll-deficient mutants, have shown a high frequency of paternal plastid transmission in alfalfa. Recent research has also shown that plastid inheritance patterns among alfalfa genotypes and are under genetic control. In a previous study we were unable to detect any correlations between qualitative, three dimensional ultrastructure of generative cells and male plastid transmission strength in certain genotypes. In the present study we used serial ultrathin sectioning, computerized reconstruction and quantitation, and stereology to further analyze generative cells within mature pollen. Measurements included volumes and surface areas of cells, nuclei, and organelles, as well as organelle number and distribution. Three genotypes were investigated, one that is a strong transmitter of male plastids (genotype 301), one that is a weaker transmitter of male plastids (genotype 7W), and a third that is an even weaker male plastid transmitter (genotype MS-5). Our results show that genotype MS-5 has significantly fewer plastids/generative cell than either of the other genotypes, which may account for it being a relatively poor transmitter of male plastids. However, plastid number does not explain known differences in male plastid inheritance between genotypes 301 and 7W, since plastid number does not differ significantly between these two genotypes. Regarding the other features of generative cells measured in this study, no consistent correlations were found that might account for differences in male plastid inheritance patterns between genotypes. Plastid distribution is equal in each end of the spindle-shaped generative cell in all genotypes studied. Similar relative results were found with regard to mitochondria within generative cells; however, comparative genetic data are not available on mitochondrial transmission patterns in alfalfa genotypes. PMID- 24221155 TI - AMMI adjustment for statistical analysis of an international wheat yield trial. AB - Multilocation trials are important for the CIMMYT Bread Wheat Program in producing high-yielding, adapted lines for a wide range of environments. This study investigated procedures for improving predictive success of a yield trial, grouping environments and genotypes into homogeneous subsets, and determining the yield stability of 18 CIMMYT bread wheats evaluated at 25 locations. Additive Main effects and Multiplicative Interaction (AMMI) analysis gave more precise estimates of genotypic yields within locations than means across replicates. This precision facilitated formation by cluster analysis of more cohesive groups of genotypes and locations for biological interpretation of interactions than occurred with unadjusted means. Locations were clustered into two subsets for which genotypes with positive interactions manifested in high, stable yields were identified. The analyses highlighted superior selections with both broad and specific adaptation. PMID- 24221156 TI - Pollen viability and pollen vigor. AB - Investigations were carried out to correlate pollen viability, assessed on the basis of a fluorochromatic reaction (FCR) test, with pollen vigor, assessed on the basis of the time taken for in vitro germination in pollen grains subjected to high humidity (>95% RH) and temperature (38 degrees C) or storage stress of Nicotiana tabacum, Agave sp., Tradescantia virginiana, and Iris sp. Both high RH and temperature, as well as storage stresses, affected pollen vigor before affecting pollen viability. The results are discussed in the light of available data on the viability and vigor of stressed pollen and of aged seeds. The need for consideration of pollen vigor, particularly in stored pollen, the inadequacy of the methods presently used, and some of the methods suitable to assess pollen vigor are elaborated. PMID- 24221157 TI - Characterization of disomic addition lines Brassica napus-Brassica nigra by isozyme, fatty acid, and RFLP markers. AB - Six Brassica napus - B. nigra disomic addition lines were characterized by isozyme, fatty acid, and RFLP markers. The markers were arranged in six synteny groups, representing six of the eight chromosomes present in the B. nigra genome. Synteny group 1 displayed high levels of linoleic and linolenic acids in the seeds of the B. nigra parent. Synteny group 3 accumulated higher levels of eicosenoic and erucic acid than B. nigra. Three of the lines transmitted the alien chromosome to 100% of the progeny. The rest had variable transmission rates but all were above 50%. Most of the lines produced disomic addition plants in their progeny, suggesting pollen transmission of the alien chromosome. In addition to the marked lines, six others remained unmarked. These could be grouped into two classes according to their alien chromosome transmission. It is likely that they represent the two other B. nigra chromosomes that remained uncharacterized by the markers. No diploid individuals carrying B. nigra genome specific markers were detected in the progenies studied. PMID- 24221158 TI - Molecular heterogeneity and genetics of Vicia faba seed storage proteins. AB - Legumin and vicilin were purified from seeds of Vicia faba L. var. Scuro, characterized in different electrophoretic systems, and used to produce polyclonal antibodies in rabbits. Two-dimensional electrophoretic studies showed a wide range of heterogeneity in the subunits of both legumin and vicilin. Legumin was found to be composed of 29 disulphide-linked subunit pairs with different molecular weight and/or isoelectric point. Western blot analysis of legumin of several mutants revealed molecular polymorphism based on a corresponding gene family. Three different alpha-major legumin patterns were found, and inheritance studies showed that the 34.3-kD legumin polypeptide is the product of one locus, Lg-1alpha, which is the first legumin genetic locus described in Vicia faba. Vicilin was found to be composed of as many as 59 subunits distributed in a molecular weight range of 65.7 to 42.8 kD (major polypeptides) and 37.2 to 15.2 kD (minor polypeptides), with different isoelectric points. A model is proposed that explains the possible formation of the minor subunits and the major subunits of 48.2 and 46 kD molecular weight (MW) from proteolytic cleavages and/or glycosilation of precursor polypeptides. Ten different vicilin electrophoretic patterns were observed among the analyzed accessions, which showed large molecular polymorphism that proved to be under genetic control. PMID- 24221159 TI - Cytological evidences of SDR-FDR mixture in the formation of 2n eggs in a potato diploid clone. AB - Macrosporogenesis and microsporogenesis were investigated in a diploid S. tuberosum x S. chacoense potato hybrid, characterized by more than 50% 2n egg formation. Fifty-five percent of dyad formation of 2n macrospores is ascribed to two meiotic abnormalities: omission of the second meiotic division, occurring at a frequency of 38%, and irregular spindle axis orientation at metaphase I at a frequency of 16%: These abnormalities give origin to a mixture of 2n eggs, composed of mostly second division restitution (SDR) and a small portion of first division restitution (FDR). Microsporogenesis showed rare dyads of 2n microspores depending on parallel spindles observed in anaphase II. PMID- 24221160 TI - Leaf physiological aspects of nitrogen-use efficiency in Brassica campestris L.: quantitative genetic variation across nutrient treatments. AB - Quantitative genetic parameters for leaf physiological and whole-plant aspects of nitrogen-use efficiency in Brassica camprestris L. were estimated in three nutrient treatments in the greenhouse. Narrow-sense heritabilities and genetic correlations varied across treatments for some traits. Sire effects were significant for leaf nitrogen content in near-optimal and super-optimal, but not in suboptimal nutrient treatments. Additive genetic variation for two estimates of leaf physiological nitrogen-use efficiency (nitrogen-based photosynthetic capacity and leaf carbon: nitrogen ratio) was significant only in the suboptimal nutrient treatment. Area-based photosynthetic capacity, on the other hand, exhibited no heritable variation in any nutrient treatment. Heritability estimates of aboveground biomass and flower production were greatest in sub- and super-optimal treatments, respectively. Negative genetic correlations between leaf nitrogen content and both estimates of leaf nitrogen-use efficiency were evident in the super-optimal treatment. Aboveground biomass and leaf nitrogen-use efficiency were positively correlated in the suboptimal treatment, suggesting that growth differences were due in part to the efficiency with which nitrogen was utilized in physiological processes. Although implications for breeding may differ for different sources of germ plasm or different measures of performance or yield, selection for improved whole-plant performance through increased nitrogen-use efficiency should proceed best in suboptimal nutrient treatments. PMID- 24221161 TI - A genome-specific repeat sequence from kiwifruit (Actinidia deliciosa var. deliciosa). AB - Six members of a family of moderately repetitive DNA sequences from kiwifruit (Actinidia deliciosa var. deliciosa) have been cloned and characterized. The repeat family is composed of elements that have a unit length of 463 bp, are highly methylated, occur in tandem arrays of at least 50 kb in length, and constitute about 0.5% of the kiwifruit genome. Individual elements diverge in nucleotide sequence by up to 5%, which suggests that the repeat sequence is evolving rapidly. Homologous sequences were found in A. deliciosa var. chlorocarpa. The repeat sequence was not found under low stringency hybridization conditions in the diploid A. chinensis, the species most closely related to the hexaploid kiwifruit, or in eight other Actinidia species. However, homologous repeats were detected in a tetraploid species, A. chrysantha. The results provide the first molecular evidence to suggest that kiwifruit may be an allopolyploid species. PMID- 24221162 TI - Prediction of F3 row performance from F2 individual plant data in oats. AB - Parameters estimated from a Gardner-Eberhart analysis of the F2 generation of a six-parent diallel in oats (Avena sativa L.) were used to compare methods for predicting the performance of F3 row plots. The prediction methods were: (1) individual F2 plant performance (F2I), (2) parent average plus F2 plot deviations (PF2), (3) parent average plus weighted F2 plot deviations (PF2P), (4) best linear unbiased prediction (BLUP) of parent average plus F2 plot deviations (BPF2), and (5) BLUP plus weighted F2 deviations (BF2). The F2 single-plant traits used for prediction were biological yield to predict F3 biological yield, whole plant and primary tiller grain yield for prediction of F3 grain yield, and whole plant and primary tiller harvest index (HI) to predict F3 HI. Prediction methods were evaluated by correlations between predicted and observed F3 performance. Prediction methods and traits for which correlations were greater than for F2I included: BF2 for biological yield, PF2, PF2P and BF2 for whole plant grain yield, PF2, BPF2, and BF2 for primary tiller grain yield. None had a correlation significantly greater than F2I for either measure of HI, where heritability was large. PF2 is the recommended method for traits with low heritability because of its simplicity and because it had the largest or nearly the largest correlation for each of the yield traits. F2I is the recommended method for traits with larger heritability. PMID- 24221163 TI - Chloroplast DNA restriction fragment length polymorphism in Sequoia sempervirens D. Don Endl., Pseudotsuga menziesii (Mirb.) Franco, Calocedrus decurrens (Torr.), and Pinus taeda L. AB - The extent and type of chloroplast DNA restriction fragment length polymorphism was determined among individual tree samples of coast redwood, Douglas fir, incense-cedar, and loblolly pine. A total of 107 trees was surveyed for three restriction enzymes (BamHI, EcoRI, HindIII) and six chloroplast DNA probes from petunia (P3, P4, P6, P8, P10, S8). The probes comprise 64% of the petunia chloroplast genome. Polymorphisms were detected in all species but loblolly pine. Coast redwood and incense-cedar had a small number of rare variants, whereas Douglas fir had one highly polymorphic region of insertions/deletions in sequences revealed by the P6 probe from petunia. The mutation hotspot is currently being studied by DNA sequence analysis. PMID- 24221164 TI - Activation of the maize transposable element Suppressor-mutator (Spm) in tissue culture. AB - Previous experiments have revealed that the maize transposable element Activator (Ac) may become active during tissue culture. The objective of the present study was to determine whether a second transposable element, Suppressor-mutator (Spm), could also be activated in tissue culture and detected in regenerated maize plants. Approximately 500 R1 progeny of 143 regenerated plants (derived from 49 embryo cell lines) were crossed as males onto an Spm-responsive tester stock. Spm activity was observed in two R1 progeny of a single regenerated plant. This plant had been regenerated from Type II (friable embryogenic) callus of an A188 * B73 genetic background after 8 months in culture; the absence of Spm activity in four other plants regenerated from this same callus demonstrates that Spm activity was not present before culturing. Approximately 20 Spm-homologous DNA sequences were detected in each of the inbreds used to initiate the tissue cultures; it is presumed that one of these became active to give rise to Spm activity. PMID- 24221165 TI - Chromosomal location of genes for Rubisco small subunit and Rubisco-binding protein in common wheat. AB - The genes coding for the Rubisco small subunit (SSU) and for the alpha-subunit of the Rubisco-binding protein were located to chromosome arms of common wheat. HindIII-digested total DNA from the hexaploid cultivar Chinese Spring and from ditelosomic and nullisomic-tetrasomic lines was probed with these two genes, whose chromosomal location was deduced from the disappearance of or from changes in the relative intensity of the relevant band(s). The Rubisco SSU pattern consisted of 14 bands, containing at least 21 different types of DNA fragments, which were allocated to two homoeologous groups: 15 to the short arm of group 2 chromosomes (4 to 2AS, 7 to 2BS, and 4 to 2DS) and 6 to the long arm of group 5 chromosomes (2 on each of arms 5AL, 5BL, and 5DL). The pattern of the Rubisco binding protein consisted of three bands, each containing one type of fragment. These fragments were located to be on the short arm of group 2 chromosomes. The restriction fragment length polymorphism (RFLP) patterns of several hexaploid and tetraploid lines were highly conserved, whereas the patterns of several of their diploid progenitors were more variable. The variations found in the polyploid species were mainly confined to the B genome. The patterns of the diploids T. monococcum var. urartu and Ae. squarrosa were similar to those of the A and D genome, respectively, in polyploid wheats. The pattern of T. monococcum var. boeoticum was different from the patterns of the A genome, and the patterns of the diploids Ae. speltoides, Ae. longissima, and Ae. Searsii differed from that of the B genome. PMID- 24221166 TI - Complementarity of genes for resistance to greenbug [Schizaphis graminum (Rondani)], biotype E, in sorghum [Sorghum bicolor (L.) Moench]. AB - Gene complementarity among various sources of resistance to greenbug biotype E was assessed. Analysis of the F2 generation of crosses between susceptible and resistant parents (mating 1) and among sources of resistance (mating 2) suggested that resistance in sorghum to greenbug biotype E was complexly inherited and, to some extent, dependent on the nature of both the resistant and susceptible parents. Positive transgressive segregation in the F2 generations of both matings was found to be due to effective plus factors, contributed by both parents in a cross, which complemented each other. The number of plus factors ranged from one to two in the susceptible parents and from two to five in the resistant parents of mating 1, and from one to five in the parents of mating 2. The consistently significant reciprocal effects shown by Sarvasi and PI264453 indicated that these sources had major factors for resistance in their cytoplasms, which were expressed in all their crosses. The results from this study indicated that the sources of resistance complemented each other to give increased number of F2 segregates with increased resistance. Thus, it should be possible to increase and diversify resistance of sorghum to greenbug biotype E by accumulating different, effective plus factors from various sources through recurrent selection. PMID- 24221167 TI - Genetic analysis of morphological variability in three Plantago species with different mating systems. AB - Morphological variability in three Plantago species possessing different mating systems - P. Major, P. coronopus, and P. lanceolata - was analyzed. From each species several populations were analyzed. In comparing the species, it appeared that both the inbreeding P. major and the outbreeding P. lanceolata showed a high degree of morphological differentiation between populations. It was hypothesized that the absence of population differentiation for the species with a mixed mating system, P. coronopus, was caused by high adaptive plasticity. Plasticity is probably the predominant mechanism by which this species copes with different environments. There were considerable differences between populations within each species for their levels of variability and their heritabilities. It appeared that besides the influence of the mating system, selection may diminish morphological variability in the case of strong directional selection, especially in P. major and P. lanceolata. PMID- 24221168 TI - Analysis of allozyme variability in three Plantago species and a comparison to morphological variability. AB - The level of electrophoretic variability in three Plantago species, P. major, P. coronopus, and P. lanceolata, was analyzed in relation to their breeding systems and compared with their morphological variability. From each species several populations were analyzed. The outcrossing P. lanceolata had the highest level of electrophoretic variability and the lowest population differentiation. The inbreeding P. major showed the opposite: a low level of electrophoretic variability and a high population differentiation. P. coronopus, with an intermediate breeding system, had an intermediate level of variability and differentiation. In comparing the species, it appeared that P. coronopus and P. major showed good concordance in the distribution of both kinds of variability, each having only a slightly higher morphological than electrophoretic differentiation between populations. P. lanceolata showed a higher morphological than electrophoretic differentiation between populations. A comparison of populations, within species, revealed good concordance of electrophoretic and morphological variability only within P. coronopus, while some populations of the other two species had relatively lower morphological variability compared with electrophoretic variability. PMID- 24221169 TI - Encoding genes for endosperm proteins in Hordeum chilense. AB - The endosperm proteins encoded by the genome Hch in Hordeum chilense, Tritordeum (amphiploid Hordeum chilense x Triticum turgidum), common wheat-H. chilense addition lines, and the segregating plants resulting from the cross Tritordeum x T. turgidum, were fractionated by three electrophoretical techniques: SDS-PAGE, A PAGE, and bidimensional PAGE. Prolamin subunits with a high molecular weight (HMW) were well visualized by SDS-PAGE, the A-PAGE technique permitted good resolution for many hordeins and gliadins, and two-dimensional electrophoresis allowed new sets of bands coded by gene complexes from H. chilense chromosomes to be distinguished. The loci Hor-Hch1 (up to 11 subunits belonging to the omega-, beta - and alpha-hordeins), Glu-Hch1 (one HMW prolamin subunit), Hor-Hch2 (one alpha-hordein), and Hor-Hch3 (up to four alpha-hordeins) were located on the H. chilense chromosomes 1Hch, 5Hch, and 7Hch. PMID- 24221170 TI - New disease resistance genes in soybean against Pseudomonas syringae pv glycinea: evidence that one of them interacts with a bacterial elicitor. AB - Soybean [Glycine max (L.) Merr.] cultivars Flambeau and Merit differed in their resistance to Pseudomonas syringae pv glycinea (Psg) race 4, carrying each of four different avirulence (avr) genes cloned from Psg or the related bacterium, Pseudomonas syringae pv tomato. Segregation data for F2 and F3 progeny of Flambeau x Merit crosses indicated that single dominant and nonallelic genes account for resistance to Psg race 4, carrying avirulence genes avrA, avrB, avrC, or avrD. Segregants were also recovered that carried all four or none of the disease resistance genes. One of the disease resistance genes (Rpg1, complementing bacterial avirulence gene B) had been described previously, but the other three genes - designated Rpg2, Rpg3, and Rpg4 - had not here to fore been defined. Rpg3 and Rpg4 are linked (40.5 +/- 3.2 recombination units). Rpg4 complements avrD, cloned from Pseudomonas syringae pv tomato, but a functional copy of this avirulence gene has not thus far been observed in Pseudomonas syringae pv glycinea. Resistance gene Rpg4 therefore may account in part for the resistance of soybean to Pseudomonas syringae pv tomato and other pathogens harboring avrD. PMID- 24221171 TI - Comment on "Selection system efficiencies for computer-simulated progeny test field designs in loblolly pine" J. A. Loo-Dinkins, C. G. Tauer and C. C. Lambeth. AB - Loo-Dinkins et al. reported relatively poor 'realized' gains from selecting individuals on departures from the means of small multi-tree plots. This could be largely attributed to disregarding a heritability of plot effects. PMID- 24221172 TI - Erratum. PMID- 24221173 TI - How sensitive is the light microscope for observations on microorganisms in natural habitats? AB - Theoretical calculations based on the depth of field of standard microscope objectives and the visual acuity of normal observors show that direct microscopy of natural samples is rarely able to reveal the presence of small microorganisms at the densities found in natural systems. Over-estimation of the importance of bacterial aggregates is also likely from an uncritical use of light microscopy. PMID- 24221174 TI - Are dissolved free amino acids free? AB - Microbial assimilation of 3 amino acids (glutamic acid, alanine, and ornithine) was characterized in 3 lakes and 2 marine stations using the Michaelis-Menten kinetic approach. The calculated Kt + Sn concentrations were related to chemical concentration measurements of dissolved free amino acids (DFAA) to evaluate the biological and the chemical determinations of the DFAA pools. Concentrations of Kt + Sn always were larger than chemical measurements of the Sn concentrations. Kt + Sn and Sn varied from 11.5 and 9.5 nM (alanine, oligotrophic lake) to 288.7 and 89.9 nM (ornithine, marine harbor station), respectively. Subtracting Sn from the Kt + Sn concentrations, Kt was found to range from 12-897% of the chemically measured Sn concentrations. To test whether the DFAA actually were free, dissolved molecules, dissolved material in the water samples was separated into various molecular size classes by means of gel permeation chromatography. From 47 116% of the DFAA in the untreated water samples was recovered in the low molecular fraction (<700 Daltons). Variation in recoveries mainly appeared to be due to an incomplete chromatographic separation and difficulties in obtaining proper blank levels. The present observations suggest that labeled tracers can be used in the study of DFAA assimilation and that the DFAA are free, dissolved molecules. This partly conflicts with previously published reports. PMID- 24221175 TI - Activities of benthic nitrifiers in streams and their role in oxygen consumption. AB - The in situ rates of oxygen consumption by benthic nitrifiers were estimated at 11 study sites in 4 streams. Two methods were used: an in situ respiration chamber method and a method involving conversion of nitrifying potential measurements to in situ rates. Estimates of benthic nitrogenous oxygen consumption (BNOC) rate ranged from 0-380 mmol of O2 m(-2).day(-1), and BNOC contributed between 0-85% of the total benthic oxygen consumption rate. The activity of nitrifiers residing in the sediments was influenced by O2 availability, temperature, pH, and substrate. Depending upon site, nitrification could approximate either first-order or zero-order kinetics with respect to ammonium concentration. The source of ammonium for benthic nitrifiers could be either totally from within the sediment or totally from the overlying water. Nitrate produced in the sediments could flux to the water above or be lost within the sediment. The sediments could act as a source (positive flux) or sink (negative flux) for both ammonium (-185 mmol.m(-2).day(-1) to +195 mmol.m( 2).day(-1)) and nitrate (-135 mmol.m(-2).day(-1) to +185 mmol.m(-2).day(-1)).This study provides evidence to suggest that measurements of down-stream mass flow changes in inorganic nitrogen forms may give poor estimates of in situ rates of nitrification in flowing waters. PMID- 24221176 TI - Benthic bacterial biomass supported by streamwater dissolved organic matter. AB - Bacterial biomass in surface sediments of a headwater stream was measured as a function of dissolved organic carbon (DOC) flux and temperature. Bacterial biomass was estimated using epifluorescence microscopic counts (EMC) and ATP determinations during exposure to streamwater containing 1,788MUg DOC/liter and after transfer to groundwater containing 693MUg DOC/liter. Numbers of bacteria and ATP concentrations averaged 1.36*10(9) cells and 1,064 ng per gram dry sediment, respectively, under initial DOC exposure. After transfer to low DOC water, biomass estimates dropped by 53 and 55% from EMC and ATP, respectively. The decline to a new steady state occurred within 4 days from ATP assays and within 11 days from EMC measures. A 4 degrees C difference during these exposures had little effect on generation times. The experiment indicated that 27.59 mg/hour of natural DOC supported a steady state bacterial biomass of approximately 10MUg C/g dry weight of sediment (from EMC determinations). Steady state bacterial biomass estimates on sediments that were previously muffled to remove organic matter were approximately 20-fold lower. The ratio of GTP?ATP indicated differences in physiological condition or community composition between natural and muffled sediments. PMID- 24221177 TI - Effects of streptomycin, cycloheximide, Fungizone, captan, carbofuran, cygon, and PCNB on soil microorganisms. AB - Eight biocides were chosen to determine whether they had any effects on nontarget organisms in soil and to what extent they would reduce their target populations under laboratory experimental conditions. A simplified microcosm system was utilized in which reduced species arrays that included field populations of either only bacteria and fungi, or bacteria, fungi, and protozoa (no nematodes, arthropods, or plants) were inoculated into sterilized soil. In a second set of experiments, plants were grown in sterilized soil. A bactericide-streptomycin four fungicides-cycloheximide, Fungizone (amphotericin B), captan, and PCNB (quintozene)-an acaricide-cygon-an insecticide-nematicide-carbofuran-and an insecticide-diazinon-were used. Each biocide had effects on nontarget organisms although the increases or decreases, with respect to the control, were of only limited duration. Reductions in target groups were typically of longer duration. Streptomycin, applied at 1 mg.g(-1) soil, did not decrease bacterial populations during the experimental incubation. At 3 mg.g(-1) soil, streptomycin decreased the numbers of bacteria that grew on tryptone agar, but also reduced active hyphae. Fungizone was the most effective of the 4 fungicides tested in reducing active hyphae. Increased bacterial populations were usually observed following fungal reductions. Carbofuran had the fewest effects on the test organisms (bacteria, fungi, and protozoa). Only an initial stimulation of bacterial and fungal populations was observed with cygon although it also increased NH4 (+)-N concentrations in soil during most of the incubation, as did streptomycin and cycloheximide. A transitory increase in fungal populations following a decrease in ciliate numbers was observed in the cygon with grazers treatments. Diazinon reduced all microbial populations and inorganic nitrogen concentrations measured. Cygon and PCNB decreased growth of blue grama plants, while streptomycin reduced shoot weights of blue grama. These results should be useful in assessing the effects of these biocides when applied to more complex systems. PMID- 24221178 TI - Absorption of pentachlorophenol (PCP) by bark chips and its role in microbial PCP degradation. AB - A pentachlorophenol (PCP)-degrading mixed bacterial population was enriched in a biofilter filled with soft wood bark chips. We found that bark chips were essential for the degradation to proceed at PCP concentrations higher than 10MUM. PCP-degrading bacteria were found to be extremely sensitive to PCP. Bark chips absorbed PCP reversibly, thus detoxifying the medium and allowing degradation to proceed at higher concentrations of PCP (beyond 200MUM). PMID- 24221179 TI - Distribution and sporulation phenology of myxomycetes in the Sonoran Desert of Arizona. AB - All pith samples from 68 dead saguaro cacti in 3 plots and 11 isolated dead plants in Saguaro National Monument, Arizona, produced at least one species of myxomycete upon incubation at 20 or 30 degrees C. Three species,Badhamia gracilis (Macbr.) Macbr.,Physarum straminipes Lister, andDidymium eremophilum M. Blackwell et Gilbertson, developed at high frequencies on the substrates in moist chamber culture.Perichaena corticalis (Batsch) Rost, andProtophysarum phloiogenum M. Blackwell et Alexopoulos were also present. Although previous literature reports [9] indicated that Myxomycetes grow best at low pH, these species all tolerated substrates of pH 8.7-10.4.Didymium eremophilum andP. phloiogenum had peaks in sporulation within 6 days; other species were slower. There was no difference in time of sporulation ofB. gracilis orD. eremophilum at 20 and 30 degrees C; however, sporulation ofP. straminipes was significantly later at 30 degrees C. Reduced spore germination and slower buildup of critically sized amoebal populations ofP. straminipes at 30 degrees C may be a factor. PMID- 24221180 TI - The ecology of the yeast flora in necroticOpuntia cacti and of associatedDrosophila in Australia. AB - A survey was made of the yeast communities isolated from necrotic tissue of 4 species of prickly-pear cacti (Opuntia stricta, O. tomentosa, O. monacantha, andO. streptacantha) which have colonized in Australia. Yeast communities were sampled from a number of localities and at different times. Cactus specific yeasts accounted for 80% of the total isolates, and the 3 most common species contributed 63% of the total. Comparisons of the species compositions of the yeast communities indicated that the differences among communities were greater betweenOpuntia species than between different localities within a single cactus species, and also that differences between years were greater than average differences between localities within years. Multivariate statistical tests of association between yeast community and physical features of rots indicated that temperature, pH, and age of rot all exerted some influence on the structure of the yeast community. Similar analyses involvingDrosophila species inhabiting these cactus rots suggested the existence of complex associations betweenDrosophila community, yeast community, and physical and chemical attributes of the cactus necroses. PMID- 24221183 TI - Evaluation of a real-time monitoring system for river quality - a trade-off between risk attitudes, costs, and uncertainty. AB - Uncertainty is definitely one of the key topics in environmental assessment and management. Typically, attempts to reduce uncertainty are subject to expenses. But how to compare and trade-off expenses and the reduced uncertainty? They only seldom allow the use of a single unit. Instead, the whole analysis and decision procedure is very subjective. This paper presents one approach to handle such problems, namely the combined use of Bayesian influence diagrams, and probabilistic risk attitude analysis. The approach was used in the evaluation of three alternatives for a real time river water quality forecasting system. A trade-off analysis of risk attitudes, costs and uncertainty indicated the levels of socioeconomic utility required for investments in the respective systems, and accordingly illuminated the impact of the uncertainties involved on inference and decision-making with various risk attitudes and discount rates. PMID- 24221184 TI - A method for facilitating the use of algae growing on tree trunks as bioindicators of air quality. AB - The abundance of epiphytic green algae has been observed to correlate strongly with air quality in several studies. In contrast to lichens, the abundance of green algae is difficult to measure accurately by visual observation. A new method based on photography and digital image processing was developed to estimate the chlorophyll content of algae growing on the bark of pine. Calibration data for the method was collected from polluted areas by spectrophotometric analysis of chlorophyll density. PMID- 24221182 TI - Role of non-electrocardiogram-gated contrast-enhanced computed tomography in the diagnosis of acute coronary syndrome. AB - Non-electrocardiogram-gated contrast-enhanced computed tomography (non-ECG-gated CT) is available in most hospitals where patients with chest and/or back pain are admitted to the emergency department. Although it has been established as the initial diagnostic imaging modality for acute aortic dissection (AAD) and pulmonary thromboembolism (PE), its diagnostic ability for acute coronary syndrome (ACS) in the emergency department has not been elucidated. We retrospectively investigated 154 consecutive patients who required non-ECG-gated CT to differentiate AAD and PE in the emergency department, but had no evidence of them on CT. Furthermore, a subanalysis was performed in the patients who were subsequently suspected of ACS and underwent emergent invasive coronary angiography followed by CT. We evaluated left ventricular enhancement to detect myocardial perfusion deficit by calculating Hounsfield units, and the results were compared with ultimate diagnoses and angiography findings. A perfusion deficit was detected in 43 patients, among whom 26 were ultimately diagnosed with acute myocardial infarction (AMI); 24 patients required emergent revascularization. The subanalysis indicated that perfusion abnormalities corresponded with the territory of the culprit artery in all except one patient. In the remaining 111 patients without perfusion deficit, only two required emergent revascularization, and their levels of creatine kinase MB were not elevated. The sensitivity, specificity, and positive and negative predictive values of non-ECG-gated CT in predicting AMI/emergent revascularization were 93 %, 87 %, 61 %, and 98 %/92 %, 85 %, 56 %, and 98 %, respectively. Non-ECG-gated CT facilitates the diagnosis of ACS and the decision on emergent catheterization, providing information on the ischemic myocardial area by detection of a localized decrease in left ventricular enhancement. PMID- 24221185 TI - A risk-based screening approach for prioritizing contaminants and exposure pathways at Superfund sites. AB - Contamination at Superfund sites can involve mixtures of chemicals and radionuclides in a variety of environmental media. Determining priorities for evaluation and remediation of various contaminants is an important part of the initial phases of any site investigation. An effective screening analysis at the beginning of the project can help by identifying both those situations in need of immediate remedial attention and those which require further sampling and evaluation. The screening approach discussed here is made up of two sets of calculations designed to provide upper- and lower-bound estimates of health risk to individuals likely to receive the highest exposures. This approach allows rapid identification of contaminants which pose a negligible risk and can be assigned a low priority for remedial attention or which pose a substantial risk and should be given the highest priority for appropriate remediation efforts. Contaminants designated as neither high- nor low-priority should be investigated in more detail prior to making decisions regarding the need for or method of remediation. The utility of this approach has already been demonstrated in the evaluation of contamination in the Clinch and Tennessee River systems originating from historical operations of atomic weapons and energy research facilities near Oak Ridge, Tennessee. PMID- 24221186 TI - Studies of the possibility of measuring changes in environmental pollution with the pixe method using moths as a monitor. AB - The possibility has been investigated of using the PIXE method to yield long and reliable time series for indicating changes in the environment, with moths or butterflies as a sample target. The suitability of this approach was demonstrated by studying standard deviations of measurements of single moths and those of populations of moths. The properties of targeting at different anatomical sites were investigated and the wing gave the most stable results, perhaps because its metabolic development is completed at the imago (newborn butterfly) stage. According to test measurements of different populations it seems possible to use moth or butterfly wing measurements to study environmental changes over the past century or so using moth or butterfly collections. PMID- 24221187 TI - The value of chick feathers to assess spatial and interspecific variation in the mercury contamination of seabirds. AB - In 1991 we compared eggs, down and body feathers of chicks of Common Terns, Herring Gulls and Black-headed Gulls in their utility to assess contamination with mercury. Like eggs feathers distinctly show interspecific and intersite differences in contamination. Highest levels were found in Common Terns, lowest in Black-headed Gulls. Chicks hatched at the Elbe had much higher mercury levels than those in other areas of the German North Sea coast. Conversion ratios between tissues have to be used with caution. PMID- 24221188 TI - Environmental variation between habitats and uptake of heavy metals by Urtica dioica. AB - The observation from previous surveys, that Urtica dioica plants that had grown in metal contaminated soil in the floodplains of the former Rhine estuary in different habitats, but at comparable total soil metal concentrations, showed significant differences in tissue metal concentrations, led to the hypothesis that variation in other environmental characteristics than soil composition and chemical speciation of metals between habitats is also important in determining uptake and translocation of metals in plants. A field survey indicated that differences in root Cd, Cu and Zn concentrations might partly be explained by variation in speciation of metals in different habitats. However, shoot concentrations showed a different pattern that did not relate to variation in soil metal concentrations. In a habitat experiment Urtica dioica plants were grown in artificially contaminated soil in pots that were placed in the four habitats (grassland, pure reed, mixed reed, osier bed) that were also included in the field survey. After seven weeks the plants showed significant differences in Cu and Zn concentrations in roots and aboveground plant parts and in distribution of the metals in the plants between habitats. It was concluded that variation between habitats in environmental characteristics other than soil composition can explain as much variation in plants as can variation in soil metal concentrations and/or speciation. The implications for assessment of soil metal contamination and uptake by plants are discussed. PMID- 24221189 TI - Issues in monitoring wilderness lake chemistry: A case study in the Sawtooth Mountains, Idaho. AB - A probability-based sample of 48 of the 152 lakes in the Sawtooth Wilderness, Idaho was conducted in summer 1988. Results from this sample were compared to the Environmental Protection Agency's 1985 probability survey of lakes throughout the western United States, which included 17 lakes in the Sawtooth Wilderness. Although methods differed in several respects, including year, season, sampling location within the lakes, holding times, and sample size, general characterization of lake chemistry for the population of lakes in the wilderness based on the two surveys was very similar. The results indicate that general lake characterization in difficult-to-access wilderness areas of the West can be achieved with a modest investment in resources with the use of volunteers. However, accurate measurement of some non-conservative and low-level analytes such as NO 3 (-) ,NH 4 (+) , total P, and aluminiun in the lakes probably requires more rigorous attention to sampling protocols and holding times. A two stage sampling strategy employing extensive use of conductivity on a large number of lakes and intensive detailed chemical characterization on a smaller number of lakes offers an alternative design for describing large populations of wilderness lakes. The relatively high concentrations of fluoride and sulfate in many of the study lakes reflect the weathering of minerals not usually identified on geologic maps. These natural sources of acid anions violate the assumptions in commonly employed empirical models of acidification. PMID- 24221191 TI - Successful conservative treatment of a candida albicans intraperitoneal mesh infection following laparoscopic ventral hernia repair. AB - INTRODUCTION: Fungal mesh infections are a poorly documented complication following abdominal wall hernia repairs. CASE REPORT: We report the case of a 65 year-old female with a Candida albicans mesh infection after laparoscopic emergency repair of a large para-umbilical hernia. She was treated conservatively with antifungal therapy and regular washouts. DISCUSSION: Mesh infections are notoriously difficult to treat and frequently require removal of the mesh. The most common pathogens are Staphylococcus species. Fungal mesh infections are uncommon and their treatment is not well documented in the literature. CONCLUSION: It is possible to treat candida albicans infection of intraperitoneal mesh without the need for surgical debridement or mesh removal by antifungal therapy and regular washouts alone. PMID- 24221190 TI - Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement. AB - Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively. Patients with different duration of RA (median 6 vs. 120 months) in the active phase of RA were enrolled in this study. We performed flow cytometric analysis of PB Th1, Th17, and Treg populations together with estimation of serum cytokine concentrations using cytometric bead array. Disease activity was calculated on the basis of clinical and biochemical indices of inflammation (DAS28, ESR, CRP). All parameters were measured and correlated with each other before and after 6 months therapy. Elevated levels of circulating Th17 cells and IL-6 were found in all active patients, of which Th17 cells were down-regulated by the treatment. Significantly reduced Th1 and functional CTLA-4+ Treg cell frequencies as well as Th1 cytokines observed only in progressive RA seemed to be irreversible. Although therapy induced clinical improvement in almost all patients, those with advanced RA remained with signs of inflammation. Our report demonstrates that both the extent of systemic immune abnormalities and their restoration are dependent on duration of the active RA. PMID- 24221192 TI - Aortic annular sizing using a novel 3-dimensional echocardiographic method: use and comparison with cardiac computed tomography. AB - BACKGROUND: Previous studies have shown cross-sectional 3-dimensional (3D) transesophageal echocardiographic (TEE) measurements to severely underestimate multidetector row computed tomographic (MDCT) measurements for the assessment of aortic annulus before transcatheter aortic valve replacement. This study compares annulus measurements from 3D-TEE using off-label use of commercially available software with MDCT measurements and assesses their ability to predict paravalvular regurgitation. METHODS AND RESULTS: One hundred patients with severe, symptomatic aortic stenosis who had both contrast MDCT and 3D-TEE for annulus assessment before balloon-expandable transcatheter aortic valve replacement were analyzed. Annulus area, perimeter, and orthogonal maximum and minimum diameters were measured. Receiver operating characteristic analysis was performed with mild or greater paravalvular regurgitation as the classification variable. Three-dimensional TEE and MDCT cross-sectional perimeter and area measurements were strongly correlated (r=0.93-0.94; P<0.0001); however, the small differences (<=1%) were statistically significant (P=0.0002 and 0.0074, respectively). Discriminatory ability for >= mild paravalvular regurgitation was good for both MDCT (area under the curve for perimeter and area cover index=0.715 and 0.709, respectively) and 3D-TEE (area under the curve for perimeter and area cover index=0.709 and 0.694, respectively). Differences in receiver operating characteristic analysis between MDCT and 3D-TEE perimeter and area cover indexes were not statistically significant (P=0.15 and 0.35, respectively). CONCLUSIONS: Annulus measurements using a new method for analyzing 3D-TEE images closely approximate those of MDCT. Annulus measurements from both modalities predict mild or greater paravalvular regurgitation with equivalent accuracy. PMID- 24221194 TI - Fertile fruit trees obtained by somatic hybridization: navel orange (Citrus sinensis) and Troyer citrange (C. sinensis x Poncirus trifoliata). AB - Nucellar cell suspension protoplasts of navel orange (Citrus sinsensis Osb.) were chemically fused with mesophyll protoplasts of Troyer citrange (C. sinensis x Poncirus trifoliata) and cultured in hormone-free Murashige and Tucker medium containing 0.6 M sucrose. Two types of plant were regenerated through embryogenesis. One type showed intermediate mono-and difoliate leaves and the other types was identical to Troyer citrange. The regenerated plants with intermediate morphology were demonstrated by chromosome counts and rDNA analysis to be amphidiploid somatic hybrids. Five clones of these somatic hybrids were grafted in the field. After 4 years, they set flowers having a morphology intermediate between those of the two parents. The pollen grains showed high stainability and sufficient germinability, and were larger than those of Troyer citrange. The fruits of the somatic hybrids were large and spherical with thick rinds. Most of them contained seeds with normal germinability. These results indicate that somatic hybridization is a useful tool for Citrus breeding. PMID- 24221195 TI - Heterochromatic differentiation in barley chromosomes revealed by C- and N banding techniques. AB - Heterochromatin distribution in barley chromosomes was investigated by analyzing the C- and N-banding patterns of four cultivars. Enzymatic maceration and air drying were employed for the preparation of the chromosome slides. Although the two banding patterns were generally similar to each other, a clear difference was observed between them at the centromeric sites on all chromosomes. Every centromeric site consisted of N-banding positive and C-banding negative (N(+) C( )) heterochromatin in every cultivar examined. An intervarietal polymorphism of heterochromatin distribution was confirmed in each of the banding techniques. The appearance frequencies of some bands were different between the two banding techniques and among the cultivars. The heterochromatic differentiation observed is discussed with respect to cause. PMID- 24221196 TI - Tissue-culture-facilitated production of aneupolyhaploid Thinopyrum ponticum and amphidiploid Hordeum violaceum x H. bogdanii and their uses in phylogenetic studies. AB - An aneupolyhaploid (2n = 36) of the decaploid Thinopyrum ponticum and an amphidiploid (2n = 28) of Hordeum violaceum x Hordeum bogdanii were produced through anther and inflorescence culture, respectively. Meiotic associations in pollen mother cells at metaphase I of these plants were analyzed. The aneupolyhaploid arose by direct embryogenesis from a microspore without passing through a callus phase. The mean pairing frequencies of 2.67 univalents (+) 0.54 rod bivalents (+) 8.85 ring bivalents (+) 2.75 trivalents (+) 0.17 chain quadrivalents (+) 0.56 ring quadrivalents (+) 0.65 pentavalents in the aneupolyhaploid (2n = 36) best fit the 2?2?1 model. However, the frequent multivalents (up to five trivalents, or three quadrivalents, or four pentavalents in a cell) indicated that decaploid T. ponticum has five sets of closely related genomes representable by the genome formula J1 J1 J1 J2 J2. Colchicine treatment of inflorescence-derived H. violaceum x H. bogdanii regenerants greatly enhanced the rate of chromosome doubling, and completely doubled regenerants could be isolated. The H. violaceum x H. bogdanii amphidiploid had a mean pairing pattern of 12.53 univalents (+) 5.57 rod bivalents (+) 1.97 ring bivalents (+) 0.07 trivalents (+) 0.03 hexavalents, indicating the presence of desynaptic gene(s) in the original diploiid hybrid. Therefore, the pairing frequency in that diploid hybrid was an under-estimate of chromosome homology between the parental genomes, and additional diploid hybrids are needed to assess the genome homology between H. violaceum and H. bogdanii. These two contrasting experiments demonstrated that tissue culture techniques are useful in altering the ploidy level to produce plant materials suitable for genome analysis and phylogenetic studies. PMID- 24221193 TI - Genomic and transcriptomic plasticity in treatment-naive ovarian cancer. AB - Intra-tumor heterogeneity is a hallmark of many cancers and may lead to therapy resistance or interfere with personalized treatment strategies. Here, we combined topographic mapping of somatic breakpoints and transcriptional profiling to probe intra-tumor heterogeneity of treatment-naive stage IIIC/IV epithelial ovarian cancer. We observed that most substantial differences in genomic rearrangement landscapes occurred between metastases in the omentum and peritoneum versus tumor sites in the ovaries. Several cancer genes such as NF1, CDKN2A, and FANCD2 were affected by lesion-specific breakpoints. Furthermore, the intra-tumor variability involved different mutational hallmarks including lesion-specific kataegis (local mutation shower coinciding with genomic breakpoints), rearrangement classes, and coding mutations. In one extreme case, we identified two independent TP53 mutations in ovary tumors and omentum/peritoneum metastases, respectively. Examination of gene expression dynamics revealed up-regulation of key cancer pathways including WNT, integrin, chemokine, and Hedgehog signaling in only subsets of tumor samples from the same patient. Finally, we took advantage of the multilevel tumor analysis to understand the effects of genomic breakpoints on qualitative and quantitative gene expression changes. We show that intra-tumor gene expression differences are caused by site-specific genomic alterations, including formation of in-frame fusion genes. These data highlight the plasticity of ovarian cancer genomes, which may contribute to their strong capacity to adapt to changing environmental conditions and give rise to the high rate of recurrent disease following standard treatment regimes. PMID- 24221197 TI - Large-scale deletions of rice plastid DNA in anther culture. AB - Plastid DNA (ptDNA) in albino rice plants regenerated from pollen by anther culture was investigated by Southern blotting. Of the 20 albino plants investigated, 7 contained ptDNA that had suffered large-scale deletion. The size and location of the deletions differed among the plants. In all cases about 30 kbp of the region containing the PstI-2 fragment (15.7 kbp) had been retained. The deleted ptDNA molecules were retained in calluses derived from the roots of each albino plant. PMID- 24221198 TI - Application of a stability statistic to international maize yield trials. AB - Genotype x environment (GE) interaction encountered in experiments complicates genotype selection and varietal recommendation. The integration of yield and stability of genotypes into a single parameter may make selection and recommendation easier. Kang developed a rank-sum method that allows selection for both yield and the stability variance statistics (sigma i (2) or s i (2) ) of Shukla. The objective of this research was to compare the rank-sum selection method to selection based on yield alone in five international maize (Zea mays L.) yield trials. Ranks were assigned for yield (the highest mean yield received a rank of 1) and for sigma i (2) and s i (2) (the lowest value received a rank of 1). The yield and sigma i (2) ranks and/or the yield and s i (2) ranks for each genotype were summed. Each trial contained two reference entries (REs). Yield rank or rank-sum of each genotype was compared to yield rank or rank-sum of the best RE (BRE). GE interaction was significant for all trials. Heterogeneity in the GE interaction due to the linear effect of a covariate (differences in fertility and/or cultural practices) was significant in Trials 1, 2, and 5. Overall, in all trials, 29 genotypes were selected on the basis of yield alone. On the basis of sigma i (2) and yield rank-sum, 32 genotypes were identified, with 11 being lower yielding than the 29 yield-based selections. On the basis of s i (2) and yield rank-sum, 31 genotypes were selected, with 11 being lower yielding than the yield-bases selections. Obviously, yield is sacrificed when the rank-sum method is used in the selection process. However, selection based on yield alone may not be adequate when GE interaction is significant because of testing in diverse environments. PMID- 24221199 TI - Efficiency of indirect selection at selection equilibrium. AB - Efficiency of indirect selection compared with that of direct selection to increase the mean value of some trait has been usually studied by considering a single generation of indirect and direct responses to selection only. However, under continued selection, genetic variances and covariances, and therefore expected genetic responses, change each generation due to linkage disequilibrium. With directional and truncation selection, genetic parameters asymptote to limiting values after several generations. The efficiency of indirect selection is examined in this limiting situation. The ratio of correlated response to direct response for the trait to improve in the limit is compared with the ratio after the first generation of selection. For all initial parameter values for which indirect selection is more efficient than direct selection, relative efficiency of indirect selection is smaller in the limit than in the first generation. For some parameter values, indirect selection is more efficient than direct selection in the first generation, but less efficient in the limit. Expressions for minimum values of the initial genetic correlation and heritability of the alternative trait required for indirect selection to be preferred in the limit are derived. These values are higher when limiting responses are used instead of single generation responses. The loss in relative efficiency of indirect selection from changes in genetic parameters due to selection should be taken into account when applications of indirect selection are considered. PMID- 24221200 TI - Components of juvenile-mature correlations in forest trees. AB - Juvenile-mature correlation has played an important role in indirect selection for size traits in forest trees. The juvenile size of a tree is a part of the mature size, and the juvenile-mature correlation is an example of a "part-whole" type of correlation. As is the case with any other "part-whole" type of correlation, the juvenile-mature correlation can be subdivided into two components; one is a function of variance only, and the other a function of variance and covariance. In this paper the components of the juvenile-mature correlation is described, the basic properties and the dynamics of its components analyzed, and the role of these components in explaining the gain from indirect juvenile selection discussed. Six forest tree populations were used to review the various properties of the model. The most important applied conclusions were: (1) even if two populations have the same juvenile-mature correlations, different selection strategies can be used depending on the nature of correlation components. (2) Choosing the proper mature age is as important as choosing juvenile age. (3) Understanding the growth curves of mean and variance is essential to developing selection strategies. PMID- 24221201 TI - A recombination hotspot in the maize A1 intragenic region. AB - We find that recombination between two alleles of the maize A1 locus that contain transposon insertions at known molecular positions can occur at 0.04-0.08 cM per kbp (centimorgan per kilobase pair), which is two orders of magnitude higher than the recombination rate for the whole maize genome. It is however, close to the rates found within the bronze locus, another maize structural gene for which both genetic and molecular data are available. This observation supports the idea that the genome consists of regions that are highly recombinogenic - in some cases, at least, structural genes - interspersed with regions that are less recombinogenic. PMID- 24221202 TI - RFLP mapping using near-isogenic lines in the soybean [Glycine max (L.) Merr]. AB - A molecular marker analysis of a near-isogenic line (NIL), its donor parent (DP), and its recurrent parent (RP) can provide information about linkages between molecular markers and a conventional marker introgressed into the NIL. If the DP and RP possess different alleles for a given molecular marker, and if the NIL possesses the same allele as the DP, then it is reasonable to presume a linkage between that molecular marker and the introgressed marker. In this study, we examined the utility of RFLPs as molecular markers for the NIL genemapping approach. The allelic status of fifteen RFLP loci was determined in 116 soybean RP/NIL/DP line sets; 66 of the 'Clark' RP type and 50 of the 'Harosoy' RP type. Of the 1740 possible allelic comparisons (116 NILs x 15 RFLP loci), 1638 were tested and 462 (33.9%) of those were informative (i.e., the RP and DP had different RFLP alleles). In 15 (3.2%) of these 462 cases the NIL possessed the DP derived RFLP allele, leading to a presumption of linkage between the RFLP locus and the introgressed conventional marker locus. Two presumptive linkages, pK-3 - and pK-472 - Lf i, were subsequently confirmed by cosegregation linkage analysis. Although not yet confirmed, two other associations, pk-7 ab and pK-229 - y 9 seemed to be plausible linkages, primarily because the pk-7 - ab association was detected in two independently derived NILs and both markers of the pK-229 - y 9 association were known to be linked to Pb. The data obtained in this investigation indicated that RFLP loci were useful molecular markers for the NIL gene-mapping technique. PMID- 24221203 TI - Organelle analysis of symmetric and asymmetric hybrids between Lycopersicon peruvianum and Lycopersicon esculentum. AB - The organelles of somatic hybrids obtained from symmetric and asymmetric fusions between the Lycopersicon species L. peruvianum and L. esculentum were analyzed by DNA hybridization methods. In the asymmetric fusions the L. peruvianum protoplasts were gamma-irradiated at a dose of 50, 300 and 1,000 Gy. The organelles were characterized using the Petunia chloroplast probe pPCY64 and the mitochondrial EcoRI-SalI fragment of the Pcf gene. In all symmetric and asymmetric hybrid plants, a total of 73 being analyzed, only one of the parental chloroplast genomes was present, except for one hybrid plant which harbored both parental chloroplast genomes. No recombination and/or rearrangement in the chloroplast genome could be identified with the pPCY64 probe. Irradiation of the L. peruvianum protoplasts did not significantly reduce the fraction of asymmetric hybrids with L. peruvianum chloroplasts. A novel mitochondrial restriction pattern was present in 5 out of 24 hybrids tested. In 9 hybrids novel combinations of chloroplasts and mitochondria were found, indicating that both organelle types sorted out independently. PMID- 24221204 TI - The use of antimicrotubule herbicides for the production of doubled haploid plants from anther-derived maize callus. AB - Four antimicrotubule herbicides, amiprophosmethyl (APM), pronamide, oryzalin, and trifluralin, were evaluated for their ability to induce chromosome doubling in anther-derived, haploid maize callus. Effects of various herbicide treatments on the growth and regenerative capacity of callus along with the ploidy and seed set of regenerated plants were determined. Flow cytometric analysis was also used to measure changes in ploidy levels of callus cells following treatments. More than 50% of the cells were doubled in chromosome number after the haploid callus was treated with 5 or 10 MU M APM or 10 MU M pronamide for 3 days. A similar proportion of plants regenerated from the treated callus produced seed upon self pollination. APM and pronamide did not inhibit callus growth at these concentrations and the treated callus retained a high plant regeneration capacity. Oryzalin very effectively induced chromosome doubling, but severely inhibited the growth of regenerable callus and plant regeneration. Trifluralin induced chromosome doubling in a small proportion of cells at lower concentrations (0.5 and 1 MU M), however, at a higher concentration (5 MUM) it inhibited callus growth and plant regeneration. The results indicate that APM and pronamide may be useful agents for inducing chromosome doubling of anther-derived maize haploid callus at very low concentrations. PMID- 24221205 TI - Quantitative genetic variance associated with chromosomal markers in segregating populations. AB - Use of chromosomal markers can accelerate genetic progress for quantitative traits in pedigree selection programs by providing early information on Mendelian segregation effects for individual progeny. Potential effectiveness of selection using markers is determined by the amount of additive genetic variance traced from parents to progeny by the markers. Theoretical equations for the amount of additive genetic variance associated with a marker were derived at the individual level and for a segregating population in joint linkage equilibrium. Factors considered were the number of quantitative trait loci linked to the marker, their individual effects, and recombination rates with the marker. Subsequently, the expected amount of genetic variance associated with a marker in a segregating population was derived. In pedigree selection programs in segregating populations, a considerable fraction of the genetic variance on a chromosome is expected to be associated with a marker located on that chromosome. For an average chromosome in the bovine, this fraction is approximately 40% of the Mendelian segregation variance contributed by the chromosome. The effects of interference and position of the marker on this expectation are relative small. Length of the chromosome has a large effect on the expected variance. Effectiveness of MAS is, however, greatly reduced by lack of polymorphism at the marker and inaccuracy of estimation of chromosome substitution effects. The size of the expected amount of genetic variance associated with a chromosomal marker indicates that, even when the marker is not the active locus, large chromosome substitution effects are not uncommon in segregating populations. PMID- 24221206 TI - Molecular and cytological evidence of deletions in alien chromosomes for two monosomic addition lines of Brassica campestris-oleracea. AB - A series of RFLP and isozyme markers were followed in the progenies of two alien addition lines of Brassica campestris-oleracea. One of the lines, carrying the C genome chromosome 4 as the alien chromosome, was surveyed for six markers. Fifty four percent of the plants carrying alien chromosomes displayed all the expected makers, whereas the rest had one to five markers missing. The second line for C genome chromosome 5 displayed a similar behavior when surveyed for three markers. All three markers were transmitted together in 46% of the plants carrying alien chromosomes, whereas the rest carried only one or two of the markers. The loss of markers was associated with reduced chromosome size caused by deletions. The observed chromosome deficiencies permitted deletion analysis for a rough physical mapping and ordering of the markers on the two C genome chromosomes. The deletions observed may represent another mechanism for molding the chromosomes of the Brassica genomes during their evolution. PMID- 24221207 TI - RFLP analysis of Zea mays callus cultures and their regenerated plants. AB - Tissue culture of the Zea mays inbred line A188 resulted in the regeneration of plants having a high level of phenotypic variation compared to seed-grown control plants. To determine how such variation was induced and whether this could be related to specific in vitro culture methods, callus cultures were established and maintained on different, commonly used culture media. Plants were regenerated and the genomic DNA of callus cultures and regenerants analysed for RFLP differences. The results show that regardless of the gene probe used, callus formation resulted in significant deviations from the DNA pattern normally found in seed-grown control plants. Alterations in gene copy number also occurred. As differentiation and organogenesis began, the level of DNA variation fell, and most of the regenerated plants showed a genetic similarity to the controls; those with RFLP differences were the somaclonal variants. PMID- 24221208 TI - On the principle underlying the tabular method to compute coancestry. AB - The tabular method to compute coancestry between two individuals is based on the principle that coancestry may be computed as the average coancestry between one individual and the parents of the other, on the condition that the former individual is not a direct descendent of the latter. It follows that coancestry also may be computed as the average of the four coancestries between the parents of the two individuals, on the condition that each individual is not a direct descendent of the other. The requirement for these conditions is explained. PMID- 24221209 TI - Genotype x strain interactions for resistance to Fusarium head blight caused by Fusarium culmorum in winter wheat. AB - In 3 consecutive years, a set of 17 winter wheat genotypes, representing a wide range of Fusarium head blight resistance, was inoculated with four strains of Fusarium culmorum. Fusarium head blight ratings were analyzed. The interaction between genotypes, strains, and years was described using a Finlay-Wilkinson model and an Additive Main effects and Multiplicative Interaction effects (AMMI) model. The interaction consisted primarily of a divergence of genotypical responses with increasing disease pressure, modified by genotype specific reactions in certain years. The divergence was mainly caused by one very pathogenic strain. The Fusarium head blight resistance in this study can be described as horizontal resistance in terms of Vanderplank, with the exception of three genotypes selected from one particular cross that showed a 'strain-year combination' dependent resistance which was ineffective in 1 year. PMID- 24221210 TI - Genetic linkage between C-bands and storage protein genes in chromosome 1B of tetraploid wheat. AB - Genetic mapping of polymorphic C-bands allows direct comparisons between genetic and physical maps. Eleven C-bands and two seed storage protein genes on chromosome 1B, polymorphic between Langdon durum and four accessions of T. dicoccoides, were used to study the distribution of recombination along the entire length of the chromosome. Recombination in the short arm was almost completely restricted to the satellite, two-thirds of the arm's length from the centromere; the Gli-B1 gene was found to be tightly linked to the telomeric C band. In the long arm, the distal 51.4% of the arm accounted for 88% of recombination; the proximal half of the arm accounted for the remaining 12%. While the amount of crossing-over differed significantly between the four T. dicoccoides 1B chromosomes, there were no significant differences in the relative distributions of crossing-over along the chromosome. Consequently, the genetic maps obtained from the four individual T. dicoccoides chromosomes were combined to yield a consensus map of 14 markers (including the centromere) for the chromosome. PMID- 24221211 TI - Genetic variation and covariation in a population of tetraploid Dactylis L. accessions. AB - Efficient utilization of divergent germ plasm sources in breeding cultivated Dactylis glomerata L. ssp. glomerata Domin depends on knowledge of quantitative variation within and among accessions. This study was undertaken to quantify variation and covariation for forage yield, maturity, disease reaction, and ground cover within a population of tetraploid Dactylis accessions. Variation was observed among families within the population for each variable. Most genetic variation (73%-93% of the family sums of squares) was within country sources or within accessions. Thus, country boundaries, which are traditionally important factors used in defining limits of plant exploration expeditions, have limited expected use in targeting future exploration for specific sources of high yield, disease resistance, or ground cover. Maturity was the exception to this; late maturing accessions were identified as originating exclusively from the USSR. Some relationships among traits, such as that for yield and disease reaction, differed for accessions and cultivars. Several accessions and families within accessions were identified to have performance superior to most or all cultivars included in this study. Existing germ plasm from several countries was identified to have potential in breeding orchardgrass, while that from other countries appeared to have little or no potential in supplying germ plasm for hay production in humid-temperate environments. PMID- 24221212 TI - Procedures for selecting composites based on prediction methods. AB - Procedures for selecting among parental varieties to be used in the synthesis of composites are discussed. In addition to the criterion based on the mean and variance of composites of the same size (k) proposed by Cordoso (1976), we suggest the index Ij=w1vj+w2 hj or I'j=(2/k) Ij for a preliminary selection among parental varieties. We show that by increasing k (size of the composite) I'j tends to gj, the general combining ability effect. Such a criterion is particularly important when n, the number of parental varieties, is large, so that the number of possible composites (Nc=2(n)-n-1) becomes too large to be handled when using the common prediction procedures. Yield data from a 9 * 9 variety diallel cross were used for illustration. PMID- 24221213 TI - Somaclonal variation in a maize inbred line is not associated with changes in the number or location of Ac-homologous sequences. AB - Somaclonal variation (tissue culture-induced mutations) may result, in some instances, from the activation of transposable elements. This study was conducted to determine whether somaclonal variants in the Zea maize L. inbred line FR27rhm were associated with movement of the transposable element Activator (Ac). Ten variants, seven of which from genetic analyses fit a single recessive gene model and three which did not due to a low number of mutant plants, were selected for analysis. Total DNA from these and from uncultured FR27rhm seedlings were examined by Southern blot analysis using the internal 1.6-kb Hind III fragment derived from the cloned Ac7 element as a probe. By using a restriction endonuclease which does not cut within the element, the number and distribution of the copies of Acrelated sequences in the FR27rhm genome could be determined. From the number of bands seen in the blots, we conclude that the FR27rhm inbred contains large numbers of Ac -related sequences. However, the pattern of bands seen in the ten variants and in the uncultured seedlings were identical, indicating that there had been no movement of any of the Acrelated sequences to cause the tissue culture-induced mutations. PMID- 24221214 TI - Insertional mutagenesis in Arabidopsis thaliana: isolation of a T-DNA-linked mutation that alters leaf morphology. AB - We investigated the potential of the Agrobacterium tumefaciens T-DNA as an insertional mutagen in Arabidopsis thaliana. Arabidopsis lines transformed with different T-DNA vectors were generated using a leaf disc infection procedure adapted for efficient selection on either kanamycin or hygromycin medium. A standardized screening procedure was developed for the detection of recessive mutations in T2 populations of regenerated and/or transformed lines. Recessive mutations originating from the tissue culture procedure occurred at a low frequency - between 2% and 5%. Within 110 transformed lines that contained a total of about 150 T-DNA inserts, one recessive mutation, named pfl, cosegregated with a specific T-DNA copy. This pfl mutation mainly affected the morphology of the first seedling leaves under normal growth conditions and was mapped to chromosome 1. No recombination between the pfl locus and the kanamycin resistance marker on the T-DNA was detected when screening F2 and F3 populations of a mutant crossed to the wild type. The maximal genetic distance between the pfl locus and the kanamycin resistance gene, determined as 0.4+/-0.4 cMorgan, strongly suggests that the pfl mutation is induced by the insertion of the T-DNA. Our finding of one T-DNA-linked recessive mutation in 110 transgenic lines indicates that T-DNA can be used for mutagenization of the Arabidopsis genome under tissue culture conditions. PMID- 24221215 TI - Impaired motor speech performance in Huntington's disease. AB - Dysarthria is a common symptom of Huntington's disease and has been reported, besides other features, to be characterized by alterations of speech rate and regularity. However, data on the specific pattern of motor speech impairment and their relationship to other motor and neuropsychological symptoms are sparse. Therefore, the aim of the present study was to describe and objectively analyse different speech parameters with special emphasis on the aspect of speech timing of connected speech and non-speech verbal utterances. 21 patients with manifest Huntington's disease and 21 age- and gender-matched healthy controls had to perform a reading task and several syllable repetition tasks. Computerized acoustic analysis of different variables for the measurement of speech rate and regularity generated a typical pattern of impaired motor speech performance with a reduction of speech rate, an increase of pauses and a marked disability to steadily repeat single syllables. Abnormalities of speech parameters were more pronounced in the subgroup of patients with Huntington's disease receiving antidopaminergic medication, but were also present in the drug-naive patients. Speech rate related to connected speech and parameters of syllable repetition showed correlations to overall motor impairment, capacity of tapping in a quantitative motor assessment and some score of cognitive function. After these preliminary data, further investigations on patients in different stages of disease are warranted to survey if the analysis of speech and non-speech verbal utterances might be a helpful additional tool for the monitoring of functional disability in Huntington's disease. PMID- 24221216 TI - Intracranial germinoma in the pineal region arising after subtotal resection of epidermoid cyst: case report. AB - We present an unusual case of a germinoma of the pineal region arising adjacent to an epidermoid cyst in a 16-year-old male. Initial imaging findings were classic for epidermoid cyst. The patient underwent two partial resections at an outside institution, each specimen demonstrating pure epidermoid cyst. Follow-up imaging over a period of 24 months showed an area of progressive contrast enhancement adjacent to the initial lesion, suggesting the development of a neoplasm. Given the area of contrast enhancement in addition to worsening headaches and visual changes, he underwent a third and final resection at our institution. Pathology revealed a mixed germ cell tumor with prominent germinoma component in addition to a well-differentiated epidermoid cyst. Details of his imaging and pathologic findings are presented, and possible explanations for these findings are explored, the most likely of which is lack of complete resection at the onset failed to identify the whole of the neoplasm. We conclude that pediatric epidermoid cysts of the pineal region should always receive close follow-up, particularly when total resection is not performed. PMID- 24221217 TI - [Multimodality and interdisciplinarity in cancer therapy : highlights of the ASCO Meeting 2013]. PMID- 24221218 TI - [The most important study results of primary chemoradiation for head and neck squamous cell carcinoma : highlights of the ASCO Meeting 2013]. AB - Primary concomitant and sequential chemoradiation is a commonly used therapeutic strategy for head and neck squamous cell carcinoma. At the annual meeting of the American Society of Clinical Oncology 2013 numerous trial results were presented. A selection of the most important trials will be summarized in this article. This year several results from phase II and III trials in concomitant and sequential therapy were demonstrated. PMID- 24221219 TI - [Therapy of recurrent and metastatic squamous cell carcinoma of the head and neck : highlights of the ASCO Meeting 2013]. AB - In many cases squamous cell carcinoma of the head and neck is already in an advanced stage when initially diagnosed. Despite definitive treatment, loco regional recurrences and metastases are common and patients ultimately require systemic treatment. Epidermal growth factor receptor (EGFR) inhibitors have proven to significantly prolong survival and have therefore become the first line treatment in recurrent and metastatic squamous cell carcinoma of the head and neck in addition to platinum and 5-FU treatment. Good results have also been reported for EGFR inhibitors in cases where platinum-based treatment has failed. Further strategies, such as salvage surgery, platinum-based chemotherapy, targeted therapy, chemoradiation and reirradiation are currently under investigation to reduce toxicity and improve survival and health-related quality of life. PMID- 24221220 TI - [Certification of head and neck tumor centers by the German Cancer Society : an overview]. AB - The German Cancer Society has certified centers of oncological care since 2003. This is realized by clearly specified criteria that are implemented in the centers' clinical practice and thus enable holistic care of oncology patients. The most important instrument here is the interdisciplinary and multiprofessional teamwork of all relevant disciplines. This transsectoral cooperation leads to continuous cooperation between out- and inpatient partners and contributes significantly to the high-quality care of oncology patients in all stages of disease. Validation of the fulfillment and implementation of the required criteria proceeds in the form of audits, the feedback from which enables the centers to continually improve their quality of care. The integration of these sustainable approaches into clinical practice not only increases patient satisfaction, but also improves the motivation of the center staff. PMID- 24221221 TI - [Language comprehension in late talkers]. AB - BACKGROUND: Late talkers (LTs) show very different courses of language development. The aim of this study was to examine whether subgrouping LTs in terms of language comprehension could allow the identification of specific subtypes with different prognoses. PATIENTS AND METHODS: Amongst other assessment strategies, standardized language (SETK-2, SETK 3-5), general nonverbal development (MFED, SON-R 21/2-7) and hearing tests (TOAE) were used to examine 48 LTs at the ages of 25 and 37 months. RESULTS: Deficits in language comprehension were recorded for 38 % of the LTs. LTs with and without impaired language comprehension differed only slightly in terms of their further language and nonverbal development, as well as in terms of anamnestic data. Comprehension of words but not of sentences proved to be a predictor of later speech impairments. CONCLUSION: Classification of LTs based on the comprehension of single words, but not of sentences or general language comprehension, at the age of 25 months can define subgroups of children with different prognoses. However, this only leads to marginal improvements in the predicted development of LTs, since substantial impairment of word comprehension is rarely observed. PMID- 24221223 TI - [A specific type of cyst]. PMID- 24221222 TI - [Sk2 guidelines"diagnosis and therapy of snoring in adults" : compiled by the sleep medicine working group of the German Society of Otorhinolaryngology, Head and Neck Surgery]. AB - These guidelines aim to facilitate high quality medical care of adults with snoring problems. The guidelines were devised for application in both in- and outpatient environments and are directed primarily at all those concerned with the diagnosis and therapy of snoring. According to the AWMF three-level concept, these represent S2k guidelines.A satisfactory definition of snoring does not currently exist. Snoring is the result of vibration of soft tissue structures in narrow regions of the upper airway during breathing while asleep. Ultimately, these vibrations are caused by the sleep-associated decrease in muscle tone in the area of the upper airway dilator muscles. A multitude of risk factors for snoring have been described and its occurrence is multifactorial. Data relating to the frequency of snoring vary widely, depending on the way in which the data are collected. Snoring is usually observed in middle-aged individuals and affected males predominate. Clinical diagnosis of snoring should comprise a free evaluation of the patient's medical history. Where possible this should also involve their bed partner and the case history can be complimented by questionnaires. To determine the airflow relevant structures, a clinical examination of the nose should be performed. This examination may also include nasal endoscopy. Examination of the oropharynx is particularly important and should be performed. The larynx and the hypopharynx should be examined. The size of the tongue and the condition of the mucous membranes should be recorded as part of the oral cavity examination, as should the results of a dental assessment. Facial skeleton morphology should be assessed for orientation purposes. Technical examinations may be advisable in individual cases. In the instance of suspected sleep-related breathing disorders, relevant comorbidities or where treatment for snoring has been requested, an objective sleep medicine examination should be performed. Snoring is not-at least as we currently understand it-a disease associated with a medical threat; therefore there is currently no medical necessity to treat the condition. All overweight patients with snoring problems should strive to lose weight. If snoring is associated with the supine position, positional therapy can be considered. Some cases of snoring can be appropriately treated using an intraoral device. Selected minimally invasive surgical procedures on the soft palate can be recommended to treat snoring, provided that examinations have revealed a suitable anatomy. The choice of technique is determined primarily by the individual anatomy. At an appropriate interval after the commencement or completion a therapeutic measure, a follow-up examination should be conducted to assess the success of the therapy and to aid in the planning of any further treatments. PMID- 24221224 TI - [Clicking larynx syndrome : a literature review and multiple-case report]. AB - BACKGROUND: A clicking noise in the larynx can probably be provoked in many adults. However, these clicks are not usually associated with pain and physicians are not consulted. The combination of a clicking larynx and pain may severely reduce an individual's quality of life. Up until now, the so-called clicking larynx syndrome (CLS) has not been defined in German teaching literature. Therefore, this article reviews the international literature on CLS and also presents three case reports. METHODS: A selective literature search using PubMed and Google was conducted. The Google search resulted in the identification of several patient forums. Three case reports are also presented (multiple-case report). RESULTS: A total of 4 studies were identified in which different kinds of clicking sounds in the larynx were described. These sounds were typically provoked by movements of the head and/or neck, swallowing or circumlaryngeal manipulation. In forums patients reported many different types of laryngeal clicking sounds, which were often described as extremely irritating. Three patients have recently presented with such symptoms at our department. DISCUSSION: The literature published on CLS suggests (although does not strictly prove) that laryngeal clicking sounds are caused by friction between the superior cornu or the top edge of the thyroid cartilage and the hyoid, or alternatively due to contact of these structure with the cervical spine. Seldom do patients report a former laryngeal trauma. The causes of the associated pain remain unclear. The treatment of choice seems to be resection of the structures associated with the clicking noise by thyroplastic surgery or reduction of the hyoid bone greater horn. It is therefore important to inform patients with mild CLS that these clicking sounds are harmless and to advise CLS patients suffering from pain of the appropriate treatment options. PMID- 24221225 TI - [Fiberoptic endoscopic evaluation of swallowing by non-medical therapists and physicians without specialist ENT or phoniatry and pediatric audiology qualifications : medical and legal aspects]. PMID- 24221227 TI - Field scale variability of cadmium and zinc in soil and barley. AB - CaCl2-extractable soil Cd and Zn contents have been suggested as a measure of bioavailability. To investigate the ability of this measure to reflect spatial patterns of Cd and Zn concentrations in barley (Hordeum vulgare L.) in an arable field, plant and soil samples were taken from a 0.5 ha area sandy soil contaminated with Cd and Zn. Cd and Zn contents in barley and yield were spatially variable. Yield was low, which may have been caused by Zn toxicity or atrazine turnover. For Cd, CaCl2-extractable soil contents explained only 17% of the variation in Cd contents in grain, and for Zn no significant correlation was observed. Nevertheless, surface plots of CaCl2-extractable soil contents and contents of barley grain illustrated their corresponding spatial patterns. Despite the poor linear correlation between CaCl2-extractable soil-Cd and grain Cd, a stochastic model for long term behaviour of Cd in field soils predicted observed variability in Cd contents of barley grain well from spatial variability of soil pH and organic matter content. The probabilistic model predicted behaviour of Cd in terms of probability, and was more appropriate than the deterministic approach. PMID- 24221226 TI - [Dysosmia : current aspects of diagnostics and therapy]. AB - Olfactory dysfunction is a common disorder, especially in elderly people. From the etiological point of view a differentiation is made between sinunasal, traumatic and non-sinunasal causes of dysosmia. Olfactory disorders are often observed in neurodegenerative diseases, especially in patients with Parkinson's disease or Alzheimer's disease. Apart from an extensive medical history important diagnostic tools are a complete ear nose and throat (ENT) examination including nasal endoscopy and olfactory testing, for example, with "sniffin' sticks". For diagnostic purposes modern imaging procedures, such as magnetic resonance imaging (MRI) are becoming more and more important. For testing children, olfactory testing needs to be adapted and depending on the etiology, olfactory training, antiphlogistic and surgical procedures are the most promising therapeutic approaches. In cases of intracranial causes of dysosmia neurosurgeons should know and respect the anatomical structures of the olfactory signal pathway, not least for the long-term prognosis. PMID- 24221228 TI - Lichen biomonitoring of trace metals in the Pistoia area (central northern Italy). AB - The epiphytic lichen Parmelia caperata (L.) Ach. was used as bioaccumulator of the heavy metals Cd, Cr, Cu, Hg, Ni, Pb and Zn in the environs of the town of Pistoia (central northern Italy). The concentrations of Cd, Cr, Ni, Hg and Pb were comparable with those found in areas not subject to atmospheric pollution. Copper and especially Zn were found in rather high concentrations. Fertilizers and pesticides were the main source of atmospheric contamination. PMID- 24221229 TI - Risk assessment of water pollutants. AB - The sources of toxic xenobiotics and different factors such as ecological diversity, differences in comparative anatomy, physiology and biochemistry, food chain variation, interrelationship within species and life span, etc., are considered during risk assessment of pollutants, and their impact on aquatic ecotoxicology is identified. A fugacity and multimedia compartment model is suggested, based on toxicodynamic (toxicity of the chemical) and toxicokinetic (metabolism of the chemical) considerations to predict and screen the behaviour of pollutants quantitatively in the aquatic environment. The significance of the risk analysis approach in anticipatory actions and regulation of pollution levels is discussed. PMID- 24221230 TI - Determination of elemental carbon emission. AB - The studies on elemental carbon content in the atmospheric air, performed at the air monitoring station in Katowice (Poland), have revealed violations of allowable maximum average annual and diurnal concentrations. Elemental carbon is introduced into the atmosphere mainly as soot generated from combustion processes. This work presents the determination of elemental carbon in emission generated from coal combustion processes. PMID- 24221231 TI - Temporal and spatial changes in primary biomass as a diagnosis and prognosis in environmental impact (Rapel Reservoir, Central Chile). AB - Extensive mortality of silversides (Atherinidae), Odontesthes bonariensis, was recorded during July 1989 in the Rapel Reservoir. Temporal and spatial changes observed in biomass concentration (chlorophyll-a) through both ground and remote sensing samples (LANDSAT), allowed us to establish a potential environmental impact. Ground measurements established an input of sulfate (SO4) in a eutrophic area. The mean concentration of biomass tended to decrease in this area in comparison with other mesotrophic areas. The local disfunction associated with the observed biomass changes has been used to develop a prediction in species composition and in biomass concentration. PMID- 24221232 TI - Trace metal residues in tissues of two crustacean species from the Bahia Blanca Estuary, Argentina. AB - Trace metals (total mercury, cadmium and zinc) were studied in several tissues of the edible shrimps Pleoticus muelleri and Artemesia longinaris from the Bahia Blanca estuary, Argentina. The digestive gland was shown to be the main organ in which metals accumulate, followed by the stomach-alimentary canal and abdominal muscle.The metal contents found in the present study largely exceeded those of the same species caught from the Argentine Sea. Mercury concentrations increased proportionally to the total length of the shrimps studied. Only little variation in metal concentrations among individuals seemed to exist.Finally, the usefulness of these species as bioindicators of trace metal pollution in the Bahia Blanca estuary is discussed. PMID- 24221233 TI - Chemical mass balance model for source apportionment of aerosols in Bombay. AB - Aerosol samples collected within an industrial region of Bombay were analyzed for elemental concentrations using inductively coupled plasma emission spectroscopy, ultraviolet/visible spectrophotometry and X-ray fluorescence spectroscopy. Nineteen elements were selected as tracers of identified sources of aerosol in the region. The U.S. EPA chemical mass balance model was employed for source apportionment. Seven major source types were identified and the performance of the model was evaluated at different sampling locations. Model results were unsatisfactory at highly polluted sites in the study regions. It was found that U.S. EPA source profiles are not suitable for such regions in India and site specific source profiles should be used in the application of chemical mass balance for source apportionment. PMID- 24221234 TI - The duckweed Wolffia globosa as an indicator of heavy metal pollution: Sensitivity to Cr and Cd. AB - The potential of Wolffia globosa, a profusely occurring rootless duckweed, was evaluated as an indicator of metal pollution in the water bodies. Plants of W. globosa were cultured in 3% Hoagland's nutrient medium which was supplemented with 0.05, 0.1, 1.0 and 2.0 mg/L of Cr and Cd. Plants showed substantial accumulation of both the metals at lowest concentrations. For example, at 0.05 ppm, the concentration factor (Cf) value for Cr was significantly higher (5616) than for Cd (1018). A high level of tolerance was shown by the plants to both Cr and Cd. The results show that the plants are sensitive to the variations in metal concentration and are capable of high metal enrichment at very low ambient concentration of the metals. This information may be useful for detecting metals in the water. PMID- 24221235 TI - Excretion of photosynthetically fixed organic carbon by metalimnetic phytoplankton. AB - The effects of light intensity, oxygen concentration, and pH on the rates of photosynthesis and net excretion by metalimnetic phytoplankton populations of Little Crooked Lake, Indiana, were studied. Photosynthetic rates increased from 1.42 to 3.14 mg C.mg(-1) chlorophylla.hour(-1) within a range of light intensities from 65 to 150MUE.m(-2).sec(-1), whereas net excretion remained constant at 0.05 mg C.mg(-1) chlorophylla.hour(-1). Bacteria assimilated approximately 50% of the carbon released by the phytoplankton under these conditions. Excreted carbon (organic compounds either assimilated by bacteria or dissolved in the lake water) was produced by phytoplankton at rates of 0.02-0.15 mg C.mg(-1) chlorophylla.hour(-1). These rates were 6%-13% of the photosynthetic rates of the phytoplankton. Both total excretion of carbon and bacterial assimilation of excreted carbon increased at high light intensities whereas net excretion remained fairly constant. Elevated oxygen concentrations in samples incubated at 150MUE. m(-2).sec(-1) decreased rates of both photosynthesis and net excretion. The photosynthetic rate increased from 3.0 to 5.0 mg C.mg(-1) chlorophylla. hour(-1) as the pH was raised from 7.5 to 8.8. Net excretion within this range decreased slightly. Calculation of total primary production using a numerical model showed that whereas 225.8 g C.m(-2) was photosynthetically fixed between 12 May and 24 August 1982, a maximum of about 9.3 g C.m(-2) was released extracellularly. PMID- 24221236 TI - Metabolic inhibition of size-fractionated marine plankton radiolabeled with amino acids, glucose, bicarbonate, and phosphate in the light and dark. AB - The effects of various metabolic inhibitors (dichlorophenyl dimethylurea, chloramphenicol, cycloheximide, carbonyl cyanide m-chlorophenyl hydrazone) on the accumulation of radiolabeled substrates (amino acids, glucose, bicarbonate, phosphate) by size-fractionated marine microbial plankton from the Sargasso Sea and the eastern Canadian arctic were studied in time-course fashion during experimental incubations either exposed to or shielded from ambient solar radiation. Picoplankton accounted for >=65% of the organic substrates and phosphate accumulated by the assemblages. The rate of organic substrate accumulation was stimulated by solar radiation in some cases but inhibited in other cases. Presumably, stimulation and inhibition co-occur and the measured response is the net result arising from these counteracting tendencies. Approximately 40% of H(14) CO3 (-) accumulation in the Sargasso Sea was associated with the picoplankton. The insensitivity of picoplankton(14)C-labeling to cycloheximide suggested active prokaryotic photosynthesis rather than heterotrophic assimilation of(14)C-labeled algal photosynthates as the route of labeling. The usefulness of some inhibitors was restricted in this study because of inconsistent correlations between the intended primary metabolic effect and the measured ecological response within the duration of the experiment. PMID- 24221237 TI - Virus adsorption to mineral surfaces is reduced by microbial overgrowth and organic coatings. AB - In experiments with strains of poliovirus, reovirus, echovirus, and Coxsackievirus, overgrowth with exopolymer-forming bacteria reduced virus adsorption to mineral surfaces. Adsorption was improved when organic materials adsorbed to minerals were removed by low-temperature ashing. In a soil series, virus adsorption increased with soil depth. This paralleled a decrease in organic content, but differences in charge development of the soil particles may also be involved. Prolonged (40-year) irrigation with treated sewage effluents, leading to a buildup of organic coatings, also decreased adsorption. However, saturation of the virus-binding capacity of the soil as a result of continuous exposure to virus-containing effluents was not apparent. PMID- 24221238 TI - Factor analysis of fluctuation in populations ofPseudomonas syringae pv.savastanoi on the phylloplane of the olive. AB - Populations ofPseudomonas syringae pv.savastanoi on the surface of olive leaves were monitored quarterly from 1974 to 1981. Seven microbiological parameters were measured: the density of the bacteria on the leaves unfolded in March, in June, and in September; the density of the bacteria on random leaves; the mean vigor of bacterial isolates obtained at each sampling time; and the similarity between the isolates, based on both the simple matching coefficient and the pattern coefficient. Seven environmental parameters were also recorded: the mean temperature, the rainfall, and the frequency and velocity of east and west winds during a period of 30 days before each sampling; the rate of turnover of the leaves during the same period; the number of pollen grains on the leaves at the time of sampling; and the 5-day biochemical oxygen demand of the wash water of leaves in each sample. Factor analysis led to extraction of 7 factors that accounted for 70.69%-92.80% of the maximum variance of every microbiological parameter and 68.92%-96.62% of the maximum variance of every environmental parameter. The factors were identified as "cambial activity", "leaf age", "summertime", "time of blossoming", "summer rains", "winter rains", and "warm weather fronts." More than 43% of the total parameter variance was loaded in the first 2 factors. Higher communality values (>86% of maximum variance) were obtained for the microbiological parameters based on the distribution of phenotypic characters among the bacterial isolates than for those based on bacterial densities on the phylloplane. PMID- 24221239 TI - Yeasts associated with pollinating bees and flower nectar. AB - A study of the yeast flora of 328 honey stomachs from 7 different pollinating bee species, and 342 flower nectar samples of 9 different flower species yielded 766 yeast isolates composed of 16 genera and 47 species. Most of the yeast species from both the sources belonged to the genusCandida, while the most frequently isolated yeasts wereDekkera intermedia from honey stomach andCandida blankii from flower nectar. Among the honey bees,Xylocopa sp., and among flowers,Citrus medica, yielded the highest number of yeast species. Nineteen species of yeasts belonging to 9 genera were common to both the sources. PMID- 24221240 TI - Association of rumen ciliate populations with plant particles in vitro. AB - Seven known species of rumen ciliates and mixedEntodinium spp. showed association with plant particles in rumen fluid in vitro. Association was greater with fresh particles than with hay, and substantially decreased when the water-soluble components of the particles were removed, suggesting that the water-soluble components may be responsible for the association. The association was rapid and maximal between 5 and 35 min (depending on the ciliate species) after exposure to the particles, and involved major transfers of ciliate populations and biomass from the liquid phase to the solid phase of the system. The most rapid and largest population transfers to the particles from the rumen fluid were shown by the holotrich ciliates, where transfers of up to 97% of the population were recorded. Association with plant particles by all species examined occurred within the pH range 5.5-7.5, and decreased with time when the particles were incubated in rumen contents in vivo. The ciliate biomass transferring from the liquid to the solid phase varied with the composition of the ciliate population. PMID- 24221241 TI - A taxonomic and ecological study of candidosis. AB - A total of 450 yeast isolates were obtained from up to 34 sites on 59 human subjects. The yeasts were characterized using morphological features and assimilation tests. Ten species were identified but, of these,Candida albicans andCandida parapsilosis were the most common and accounted for 84% of the isolates. An examination of the biotypes of the various species indicated a much greater diversity in the yeast microflora than that detected by species identifications alone. Fifty-five biotypes were differentiated and it is suggested that these could be regarded as distinct taxonomic or ecological entities. PMID- 24221242 TI - Comparison of conventional and miniaturized biochemical techniques for identification of animal streptococcal isolates. AB - Human clinical streptococcal isolates can be identified rapidly by means of commercially available miniaturized biochemical systems, in contrast to animal and environmental isolates which may require extensive characterization using conventional methods. Streptococcal isolates (n=548) from fresh animal feces of cattle, swine, and broiler chickens were tested by means of conventional biochemical and physiological techniques, and also with a miniaturized technique in which conventional formulations were dispensed in 0.1 ml volume into microtiter plates. Agreement of the positive feature frequencies of the two methods were compared. Results from the tolerance tests in the two methods were generally in good agreement. However, the miniaturized method tended to give false negative results in some carbohydrate fermentation tests. Agreement between the 2 methods ranged from 100% for bile esculin tests to 71% for raffinose fermentation. Cluster analysis of the conventional method data indicated that there were 11 biochemically related groups of isolates, 2 of which were identified asStreptococcus faecalis, andS. morbillorum. Half of the isolates biochemically resembledS. faecium. Errors of miniaturized tests occurred mainly in certain tests and in certain biochemically related clusters of isolates. The data indicate that further investigation of experimental conditions such as medium formulation and inoculum size could lead to a successful miniaturized technique for testing animal streptococcal isolates. PMID- 24221243 TI - Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer. AB - PURPOSE: To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer. METHODS: A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces). RESULTS: Of the 89 PET scans, 52 (58.4%) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2% of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of >=12 months had such disease (P = 0.0031). CONCLUSION: PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of >=12 months are the best candidates for cytoreductive surgery. PMID- 24221244 TI - Peptide receptor radionuclide therapy for neuroendocrine tumours: standardized and randomized, or personalized? PMID- 24221245 TI - Patellofemoral pain syndrome. AB - The patellofemoral pain syndrome (PFPS) is a possible cause for anterior knee pain, which predominantly affects young female patients without any structural changes such as increased Q-angle or significant chondral damage. This literature review has shown that PFPS development is probably multifactorial with various functional disorders of the lower extremity. Biomechanical studies described patellar maltracking and dynamic valgus in PFPS patients (functional malalignment). Causes for the dynamic valgus may be decreased strength of the hip abductors or abnormal rear-foot eversion with pes pronatus valgus. PFPS is further associated with vastus medialis/vastus lateralis dysbalance, hamstring tightness or iliotibial tract tightness. The literature provides evidence for a multimodal non-operative therapy concept with short-term use of NSAIDs, short term use of a medially directed tape and exercise programmes with the inclusion of the lower extremity, and hip and trunk muscles. There is also evidence for the use of patellar braces and foot orthosis. A randomized controlled trial has shown that arthroscopy is not the treatment of choice for treatment of PFPS without any structural changes. Patients with anterior knee pain have to be examined carefully with regard to functional causes for a PFPS. The treatment of PFPS patients is non-operative and should address the functional causes. LEVEL OF EVIDENCE: V. PMID- 24221246 TI - Distinctive collagen maturation process in fibroblasts derived from rabbit anterior cruciate ligament, medial collateral ligament, and patellar tendon in vitro. AB - PURPOSE: Differences in the tissue-specific collagen maturation process between tendon and ligament are still unknown. Collagen cross-link formation is crucial for the collagen maturation process. The aim of this study is to examine collagen maturation processes of anterior cruciate ligament (ACL), medial collateral ligament (MCL), and patellar tendon (PT) in vitro, in order to determine the optimal cell source for tissue engineering of ligament. METHODS: Cells derived from the ACL, MCL, and PT of New Zealand white rabbits were isolated. Each cell type was cultured for up to 4 weeks after reaching confluence. Cell-matrix layers were evaluated and compared for their morphology, collagen cross-links, and gene expression levels of lysine hydroxylase 1 and 2, lysyl oxidase (LOX), tenomodulin, collagen1A1 (Col1A1), and collagen3A1 (Col3A1). RESULTS: Transmission electron microscopy photomicrographs verified that collagen fibrils were secreted from all three types of fibroblasts. A higher ratio of dihydroxylysinonorleucine/hydroxylysinonorleucine was evident in the ligament compared to the tendon, which was consistent with lysine hydroxylase 2/lysine hydroxylase 1 gene expression. The gene expression of LOX, which regulates the total amount of enzymatic cross-linking, and the gene expression levels of Col1A1 and Col3A1 were higher in the ACL matrix than in the MCL and PT matrices. CONCLUSION: ACL, MCL, and PT cells have distinct collagen maturation processes at the cellular level. In addition, the collagen maturation of ACL cells is not necessarily inferior to that of MCL and PT cells in that all three cell types have a good ability to synthesize collagen and induce collagen maturation. This bioactivity of ACL cells in terms of ligament-specific mature collagen induction can be applied to tissue-engineered ACL reconstruction or remnant preserving procedure with ACL reconstruction. PMID- 24221248 TI - Sequence-modified primers for the differential RT-PCR detection of Andean potato latent and Andean potato mild mosaic viruses in quarantine tests. AB - To enable the differential PCR detection of Andean potato latent virus (APLV) and Andean potato mild mosaic virus (APMMV) strains, sense primers were designed that correspond to regions directly upstream of the coat protein genes. Their differentiating power was increased by A->C or T->C replacements in their 3' terminal parts. Together with the broad-specificity antisense primer EM3, primer AL-a-mod3C detected all APLV strains tested, but none of the APMMV strains. Primer AM-a-mod4C yielded PCR products with all APMMV preparations, but also with some APLV preparations. Sequence analysis revealed that this was not due to a lack of primer specificity, but to the sensitive detection of contaminating APMMV in some of our APLV preparations. PMID- 24221247 TI - Genetic heterogeneity in the leader and P1-coding regions of foot-and-mouth disease virus serotypes A and O in Africa. AB - Genetic information regarding the leader (L) and complete capsid-coding (P1) region of FMD serotype A and O viruses prevalent on the African continent is lacking. Here, we present the complete L-P1 sequences for eight serotype A and nine serotype O viruses recovered from FMDV outbreaks in East and West Africa over the last 33 years. Phylogenetic analysis of the P1 and capsid-coding regions revealed that the African isolates grouped according to serotype, and certain clusters were indicative of transboundary as well as intra-regional spread of the virus. However, similar analysis of the L region revealed random groupings of isolates from serotypes O and A. Comparisons between the phylogenetic trees derived from the structural coding regions and the L region pointed to a possibility of genetic recombination. The intertypic nucleotide and amino acid variation of all the isolates in this study supported results from previous studies where the externally located 1D was the most variable whilst the internally located 1A was the most conserved, which likely reflects the selective pressures on these proteins. Amino acids identified previously as important for FMDV structure and functioning were found to be highly conserved. The information gained from this study will contribute to the construction of structurally designed FMDV vaccines in Africa. PMID- 24221249 TI - Production and immunogenicity of VP2 protein of porcine parvovirus expressed in Pichia pastoris. AB - Viral protein 2 (VP2) of porcine parvovirus (PPV) is the major viral structural protein and is responsible for eliciting neutralizing antibodies in immunized animals. In this study, we constructed and characterized a recombinant yeast vector encoding the VP2 protein, designated as pGAPZalphaA-VP2. The construct was confirmed by restriction enzyme digestion, PCR, and sequencing and then introduced into P. pastoris strain SMD1168 by electroporation. The expressed VP2 protein was analyzed by SDS-PAGE and western blot. Immunization of mice with the VP2 protein elicited a PPV-specific humoral immune response. Notably, a preparation of VP2 protein containing adjuvant induced a much better antibody response than VP2 alone. Clearly, the adjuvant strongly enhanced the immunogenicity of VP2. This study provides a foundation for the application of the VP2 protein in the clinical diagnosis of PPV and in vaccination against PPV in the future. PMID- 24221250 TI - The membrane on the surface of hepatitis E virus particles is derived from the intracellular membrane and contains trans-Golgi network protein 2. AB - Our previous studies demonstrated that hepatitis E virus (HEV) requires the multivesicular body (MVB) pathway to release virus particles, suggesting that HEV utilizes the cellular ESCRT machinery in the cytoplasm, not at the cell surface, to be released from infected cells. In this study, we generated a murine monoclonal antibody (mAb) against the membrane-associated HEV particles to examine whether the membrane is derived from intracellular vesicles or the cell surface. An established mAb, TA1708, was found to capture the membrane-associated HEV particles, but not the membrane-dissociated particles or fecal HEV, in an immunocapture RT-PCR assay. Furthermore, digitonin treatment confirmed that the membrane on the surface of cell-culture-generated HEV particles was a lipid membrane. Double immunofluorescence staining revealed that mAb TA1708 specifically recognizes trans-Golgi network protein 2 (TGOLN2), an intracellular antigen derived from the trans-Golgi network. Supporting these findings, HEV particles with lipid membranes and ORF3 proteins on their surface were found abundantly in the lysates of HEV-infected cells. These results indicate that HEV forms membrane-associated particles in the cytoplasm, most likely by budding into intracellular vesicles, and that the released HEV particles with a lipid membrane retain the antigenicity of TGOLN2 on their surface. PMID- 24221251 TI - Molecular detection of human parechovirus in children with acute gastroenteritis in Guangzhou, China. AB - Human parechoviruses (HPeVs) are widespread pathogens causing a wide spectrum of diseases. The prevalence and genetic diversity of HPeV in children with acute diarrhea in China is not well known. The purpose of this study was to investigate the epidemiological characteristics of HPeV in Guangzhou, China. A total of 328 stool specimens collected from children under the age of 5 years with acute diarrhea were tested for the presence of HPeV. Of these, 44 (13.4 %, 44/328) were HPeV positive, with the majority of the infected children (97.7 %, 43/44) being younger than two years of age. HPeV was more frequently detected during July and August. The epidemiological profile of co-infections was similar to that observed in a previous study. Six different HPeV genotypes, including HPeV1, -3, -4, -5, 6, and -14, were identified, and of these, HPeV14, a rarely reported genotype, was reported for the first time in children with acute gastroenteritis in China. In summary, this study clearly demonstrated that HPeV circulating in Guangzhou, China, is genetically diverse, including six genotypes, and it provides useful epidemiological data on the features of HPeV infection in this area. PMID- 24221252 TI - ypN0 nodal status after neoadjuvant chemoradiotherapy for rectal carcinoma is not associated with adverse prognosis as compared with pN0 after primary surgery. AB - BACKGROUND AND AIMS: Neoadjuvant chemoradiotherapy (nCRT) has been established as standard treatment for locally advanced rectal cancer (cT3/4 or cN+ cM0, distance from circumferential resection margin <=1 mm) to enhance local disease control and minimize the rate of locoregional recurrence. As a consequence of downstaging, a significant proportion of patients show non-viable tumor deposits within regional lymph nodes that qualify as ypN0 according to the current TNM classification irrespective of the actual pre-treatment status. Accordingly, the prognostic relevance of ypN0 status as compared with true pN0 without preceding nCRT is not known. PATIENTS AND METHODS: We retrospectively analyzed 132 patients who underwent standard total mesorectal excision (TME) surgery after nCRT for rectal carcinoma and were classified as ypN0, and compared their prognoses with those of 341 patients with pN0 without nCRT. RESULTS: Re-evaluation of regional lymph nodes after nCRT showed no evidence of previous metastasis in 91 cases (ypN0(-)), sure but non-viable metastasis in 14 patients (ypN0(+)), and unsure status in 27 patients (ypN0(X)). The local recurrence rate, distant metastases, and disease-free, observed, and cancer-related survival were similar in all subgroups (p = 0.447, 0.695, 0.759, 0.655, and 0.354, respectively). CONCLUSION: Our results showed a similar outcome in patients with ypN0 and in the control group with pN0 regarding local recurrence rate, distant metastases, and disease free, observed, and cancer-related survival. Validation of these results is necessary to clarify the questions regarding postoperative adjuvant chemotherapy for patients with ypN0(+). PMID- 24221253 TI - Adenocarcinoma arising from a long-standing Kock pouch. PMID- 24221254 TI - Efficient production of wheat-barley hybrids and preferential elimination of barley chromosomes. AB - Intergeneric hybridization between four common wheat cultivars, Triticum aestivum L. cultivars Chinese Spring, Norin 12, Norin 61, and Shinchunaga, and cultivated barley, Hordeum vulgare L. cultivars Betzes, Nyugoruden, Harunanijou, and Kinai 5 were carried out in a greenhouse under 15 - 20 degrees C and long-day (15 h) photoperiod conditions. Two days prior to pollination, a 100 mg/1 2,4-D solution was injected into wheat stems. Among wheat cultivars, Norin 12, Norin 61, and Shinchunaga showed higher crossabilities than that of Chinese Spring, suggesting the presence of crossability gene(s) other than the kr system of Chinese Spring. Variation was also found among the barley cultivars as male parents. Betzes barley showed the highest crossability with wheat. Thus, the cross Norin 12*Betzes showed the highest crossability (8.25%), followed by Norin 61 *Betzes (6.04%), Shinchunaga*Betzes (5.00%), and Shinchunaga*Kinai 5 (5.00%). The embryos were rescued by culture at 15-20 days after pollination. Seventyfour plants were obtained from 82 embryos. The morphology of the hybrid plants resembled that of wheat parents. Among 60 seedlings observed, 28 had 28 chromosomes, 8 had 21, 23 had aneuploid numbers of chromosomes (22-27), and 1 had 29 chromosomes. About half of the aneuploid hybrids showed mosaicism for chromosome number. By analyzing five isozyme markers of barley chromosomes, the chromosome constitutions of the aneuploid hybrids were determined. Barley chromosomes 1 and 5 were found to be preferentially eliminated in the hybrids, while chromosomes 2 and 4 were eliminated infrequently. The conditions and genetic factors for high crossability and the tendency of barley chromosome elimination are discussed. PMID- 24221255 TI - Selection of a mutation conferring high NaCl tolerance to gametophytes of Ceratopteris. AB - Spores from a weakly salt tolerant strain of Ceratopteris richardii containing the mutation stl1 were irradiated and sown on nutrient medium supplemented with 200 mM NaCl. A single highly salt tolerant gametophyte was recovered and selfed to generate a homozygous sporophyte. Spores from this strain, 10alpha23, were used to document the sexual transmission of the trait and to monitor the inheritance of tolerance in crosses to both the wild type and to the parental salt tolerant strain. Genetic analysis showed the 10alpha23 strain to possess both the original stl1 mutation and an additional semi-dominant nuclear mutation, stl2, that individually conferred a high level of tolerance to gametophytes. In combination, both mutations had additive effects. Tolerance was also evident in sporophytes, but at a lower level than in gametophytes. PMID- 24221256 TI - Selection for increased percentage phaseolin in common bean : 1. Comparison of selection for seed protein alleles and S1 family recurrent selection. AB - Two selection methods were compared to determine which was more efficient for increasing percentage phaseolin in the common bean (Phaseolus vulgaris L.). A base population consisting of families segregating for six seed protein alleles (Phas (S) , Phas (C) , Phas (T) , phas (-), lec(-), and Arcl (+)), all of which have measurable effects on percentage phaseolin, was subjected to either three cycles of S1 family recurrent selection for increased percentage phaseolin (PPS), or one cycle of selection for combinations of the protein alleles (PAS) known to have positive effects on phaseolin accumulation. One cycle of PAS resulted in an increase in percentage phaseolin that was equivalent to three cycles of PPS. Selection under both methods produced increases in several correlated traits including percentage total protein, phaseolin as a percent of total protein, mg protein/seed, and mg phaseolin/seed. The amount of nonphaseolin protein per seed decreased, while seed yield was unaffected by either selection procedure. By selecting for favorable seed protein alleles identified by electrophoresis, it was possible to rapidly increase percentage phaseolin without the need for field evaluation. PMID- 24221257 TI - Selection for increased percentage phaseolin in common bean : 2. Changes in frequency of seed protein alleles with S1 family recurrent selection. AB - Recurrent selection methods are designed to increase the frequency of favorable alleles within a population(s) with each cycle of selection. Yet it is likely that different methods will change allele frequencies at different rates or may act on different alleles. To investigate the ability of S1 family selection to shift the frequencies of favorable alleles within a population of Phaseolus vulgaris (L.), we examined the changes in frequencies of six alleles (Phas (S) , Phas (C) , Phas (T) , phas (-), lec (-), and Arc1 (+)) that affect the amount of phaseolin accumulated in seeds, over three cycles of selection for increased percentage phaseolin (PPS). The frequency of alleles Phas (C) and lec (-), both of which have positive effects on percentage phaseolin, increased with selection while the frequencies of phas (-) and Arc1 (+), which have strong negative effects, decreased. The frequencies of the Phas (S) and Phas (T) alleles showed no linear trends with selection, indicating that the frequency changes may be due to random drift and not to the selection procedure. The proportion of the phenotypic variation (R (2)) for percentage phaseolin that was explained by each of the alleles, and by all the alleles combined, changed with each cycle of selection. In most cases the change resulted in a decrease in the R (2) value. In this population, S1 family selection was effective at increasing the frequencies of all favorable alleles except Phas (T) , and rapidly decreased the frequencies of deleterious alleles. PMID- 24221258 TI - Hybridization between Triticum aestivum L. and Agropyron michnoi Roshev. : 1. Production and cytogenetic study of F1 hybrids. AB - Intergeneric hybrids between Triticum aestivum cv 'Chinese Spring' (2n=6x=42, AABBDD) and Agropyron michnoi Roshev. (2n=4x=28, PPPP) were obtained by embryo culture. Their spike characteristics were similar to those of common wheat but, unlike their parents, they were long-awned. The average meiotic chromosome pairing at MI of F1 hybrids was: 6.39 I +3.75 rodII+8.64 ringII+0.81 III+0.30 IV+0.04 V, the bivalent and multivalent formation of which was much higher than expected from the genomic formulae. It is especially worthwhile to note that the F1 hybrids were self-fertile, self set being 0.15%, and seeds were easily obtained from the backcross of f1 plants with hexaploid and tetraploid wheats; here the seed set was more than 20.0%. The polyploid taxa and the position of A. Michnoi in Agropyron are discussed. PMID- 24221259 TI - P element transposon-induced quantitative genetic variation for inebriation time in Drosophila melanogaster. AB - Bi-directional selection was carried out in coisogenic stocks with and without mobilised P element transposons to determine whether P elements induce quantitative genetic variation for inebriation time in Drosophila. There was significant response to 11 generations of selection in both pairs of replicates of bi-directional selection from an isogenic base stock in which P elements had been mobilised. Conversely, there was no significant response to 11 generations of identical selection in the control lines derived from a relatively inbred line lacking P elements. Thus, P elements have induced quantitative genetic variation for inebriation time. PMID- 24221260 TI - Genetic analysis of salt tolerance during germination in Lycopersicon. AB - The salt-tolerant cultivated tomato (Lycopersicon esculentum) accession, 'PI174263', and a sensitive cv, 'UCT5', were crossed to develop reciprocal F1, F2 and BC1 populations for genetic analysis of salt tolerance in tomatoes during seed germination. Variation was partitioned into embryo, endosperm and maternal (testa and cytoplasmic) components. Generation means analysis indicated that there were no significant embryo (additive, dominance or epistatic) effects on germination performance under salt stress. Highly significant endosperm additive and testa dominance effects were detected. The proportion of the total variance explained by the model containing these two components was R(2)=98.2%. Variance component analysis indicated a large genetic variance with additive gene action as the predominant component. Furhter inspection indicated that this variance was attributable to endosperm additive effects on germinability under salt stress. Narrow-sense heritability was estimated as moderately high. Implications for breeding procedures are discussed. PMID- 24221261 TI - Decreased frequency of the rat growth hormone transgene in mouse populations with or without selection for increased adult body weight. AB - Frequencies of mice with the rat growth hormone (rGH) transgene were examined in lines derived from two genetic bases (P/W and P/C). The genetic bases were developed from males (P) with the rGH transgene, mated with non-transgenic females of different origin: a line previously selected for large body size (W) and a corresponding unselected control line (C). They were maintained for six generations under random mating with or without selection for increased 42-day body weight. The frequencies of P/W and P/C males with the rGH transgene wer 0.075 and 0.300, respectively at generation 0 of the genetic bases. They were significantly (P<0.05) lower than the expected frequency (about 0.5). At generation 6, the frequencies had decreased further both in selected and unselected lines (ranging from 0.025 to 0.125). Decreased frequencies of mice with the transgene were confirmed in a separate experiment testing segregation of the transgene. The reasons for these decreases are not clear. The results suggest that transgenes need to be monitored when transgenic animals are mated with animals of different origin. PMID- 24221262 TI - Using molecular markers to map multiple quantitative trait loci: models for backcross, recombinant inbred, and doubled haploid progeny. AB - To maximize parameter estimation efficiency and statistical power and to estimate epistasis, the parameters of multiple quantitative trait loci (QTLs) must be simultaneously estimated. If multiple QTL affect a trait, then estimates of means of QTL genotypes from individual locus models are statistically biased. In this paper, I describe methods for estimating means of QTL genotypes and recombination frequencies between marker and quantitative trait loci using multilocus backcross, doubled haploid, recombinant inbred, and testcross progeny models. Expected values of marker genotype means were defined using no double or multiple crossover frequencies and flanking markers for linked and unlinked quantitative trait loci. The expected values for a particular model comprise a system of nonlinear equations that can be solved using an interative algorithm, e.g., the Gauss-Newton algorithm. The solutions are maximum likelihood estimates when the errors are normally distributed. A linear model for estimating the parameters of unlinked quantitative trait loci was found by transforming the nonlinear model. Recombination frequency estimators were defined using this linear model. Certain means of linked QTLs are less efficiently estimated than means of unlinked QTLs. PMID- 24221263 TI - Tomato cybrids with mitochondrial DNA from Lycopersicon pennelli. AB - Cybrids have been regenerated following protoplast fusion of iodoacetamide treated leaf mesophyll cells of Lycopersion esculentum cv UC82 and gamma irradiated cell suspensions of L. pennellii, LA716. The cybrids were recovered in the regenerant population at a frequency of 19%, no selection pressure was applied for the persistence of the donor cytoplasm. The nuclear genotype of ten cybrids was characterized extensively using isozyme markers, cDNA-based restriction fragment length polymorphisms (RFLPs), and the morphology of the plants. No nuclear genetic information from L. pennellii was detected in the cybrids. The organellar genotype of the cybrids was determined using cloned probes and species-specific RFLPs. All the cybrids had inherited the tomato chloroplast genome and had varying amounts of L. pennellii mitochondrial DNA. The cybrids all had a diploid chromosome number of 24, produced pollen, and set seed. PMID- 24221264 TI - Molecular and cytological characterization of repetitive DNA sequences in Brassica. AB - We isolated three different repetitive DNA sequences from B. campestris and determined their nucleotide sequences. In order to analyze organization of these repetitive sequences in Brassica, Southern blot hybridization and in situ hybridization with metaphase chromosomes were performed. The sequence cloned in the plasmid pCS1 represented a middle repetitive sequence present only in B. campestris and not detected in closely related B. Oleracea. This sequence was localized at centromeric regions of six specific chromosomes of B. campestris. The second plasmid, pBT4, contained a part of the 25S ribosomal RNA gene, and its copy number was estimated to be 1,590 and 1,300 per haploid genome for B. campestris and B. oleracea, respectively. In situ hybridization with this sequence showed a clear signal at the NOR region found in the second largest chromosome of B. Campestris. The third plasmid, pBT11, contained a 175-bp insert that belongs to a major family of tandem repeats found in all the Brassica species. This sequence was detected at centromeric regions of all the B. campestris chromosomes. Our study indicates that in situ hybridization with various types of repetitive sequences should give important information on the evolution of repetitive DNA in Brassica species. PMID- 24221265 TI - In situ hybridization with species-specific DNA probes gives evidence for asymmetric nature of Brassica hybrids obtained by X-ray fusion. AB - We have previously reported production of somatic hybrids between B. oleracea and B. campestris by fusion of B. oleracea protoplasts with X-irradiated B. campestris protoplasts, in order to transfer a part of the B. campestris genome into B. Oleracea. Our previous analysis of morphology, chromosome number, and isozyme patterns of the hybrids suggested that they are asymmetric in nature. To obtain further evidence for the asymmetric nature of the hybrids, we isolated B. campestris-specific repetitive sequences and used them for in situ hybridization of the chromosomes of the hybrids. The repetitive DNA probes could specifically identify 8 out of 20 chromosomes of the B. campestris genome, and analysis of the hybrids indicates that 1-3 chromosomes of B. campestris are lacking in all five hybrids examined, giving clear evidence for the asymmetric nature of the hybrids. Furthermore, in situ hybridization revealed that some of the abnormal chromosomes observed in the hybrids are generated by rearrangements of B. Campestris chromosomes caused by X-irradiation. Altogether, our study indicates that in situ hybridization using species-specific repetitive sequences is a useful tool to analyze chromosomal compositions of various types of hybrids obtained by cell fusion or conventional methods. PMID- 24221266 TI - Expression of Thinopyrum distichum NORs in wheat*Thinopyrum amphiploids and their backcross generations. AB - The C-banding pattern of the satellited chromosomes in Thinopyrum distichum and Triticum durum was established. Both T. durum and Th. distichum contained two pairs of satellited chromosomes, which could be distinguished from one another. In the amphiploids [T. durum*Th. distichum (2x=56)] and in the backcross T. durum/(T. durum*Th. distichum)(2), BC1F3, and BC1F5 (2n = 42) the satellite was visible on only 1B and 6B of T. durum. The vector pTa 71 containing the rRNA gene from wheat hybridized to two pairs of chromosomes (four hybridization sites) in T. durum and Th. distichum, to eight sites in the amphiploid hybrid (2n=56), and to six sites in the backcross populations BC1F1. BC1F3, and BC1F5 (2n=42). The two satellite pairs in Th. distichum could be distinguished by the chromosomal location of the rRNA site (median or subterminal) and by the centromere position. One copy of each pair was present in the BC1F1, but in the BC1F3 and BC1F5 populations the pair with the subterminal location of rRNA genes was absent. Silver nitrate staining indicated that the rRNA genes of T. durum did not completely suppress those of Th. distichum. The octoploid amphiploid (2n = 56) contained a maximum of four large and four small nucleoli and the hexaploid BC1s (2n=42), four large and two small nucleoli. PMID- 24221267 TI - The cytological and genetic characterisation of doubled haploid lines derived from triticale*wheat hybrids. AB - Anther culture, when applied to hexaploid triticale*wheat hybrids, offers the opportunity to re-assort wheat D genome and rye R genome chromosomes into homozygous doubled haploid lines in a single generation. The characterisation of such lines is the first step in their utilisation in wheat improvement. Two lines, M24 and M25 from the cross of 'Beagle'*'Kedong 58', and one line, M27, from the cross 'Beagle'*'Jinghua No. 1' have been characterised using different methods including conventional cytology and chromosome banding, and by using marker systems for storage protein composition (glutenins and gliadins), isozymes (alpha-amylase, aminopeptidase, glutamate oxaloacetic transaminase (GOT)) and RFLP markers. The results from all approaches were consistent in proving that M24 is a whole chromosome 6R/6D substitution line, while M25 and M27 are whole chromosome 1R/1D substitution lines. The relative advantages and disadvantages of each method of identification are also discussed. PMID- 24221268 TI - Identification and genetic analysis of semidwarfism-related proteins in rice (Oryza sativa L.). AB - By transferring a semidwarf gene (sd-1) from Taichung Native 1 into a tall Japanese cultivar, Norin 29, through seven backcrosses, a semidwarf near-isogenic line SC-TN1 was obtained. The proteins of the embryo in Norin 29 and SC-TN1 were separated by two-dimensional electrophoresis. Most of the proteins showed the same electrophoretic pattern. However, it was found that there was a difference in the appearance of two basic glycoproteins designated as SRP-1 and SRP-2. These proteins exhibited the same molecular mass, but different isoelectric points. Hybridization results indicated that a single locus controls SRP-1 and SRP-2 with codominant alleles. The gene symbol Srp was given to this locus, with alleles Srp 1 and Srp-2 responsible for SRP-1 and SRP-2, respectively. Srp-2 was found in all of the semidwarf cultivars and lines having sd-1, except a tall cultivar Tsaiyuan chung. This finding suggests that Srp-2 may be closely linked with sd-1. The amounts of these proteins markedly increased after water absorption of the seed, suggesting that these proteins may be related to the early development of the plant. PMID- 24221269 TI - Identification of alien chromatin specifying resistance to wheat streak mosaic and greenbug in wheat germ plasm by C-banding and in situ hybridization. AB - The chromosome constitutions of eight wheat streak mosaic virus (WSMV)-resistant lines, three of which are also greenbug resistant, derived from wheat/ Agropyron intermedium/Aegilops speltoides crosses were analyzed by C-banding and in situ hybridization. All lines could be traced back to CI15092 in which chromosome 4A is substituted for by an Ag. intermedium chromosome designated 4Ai-2, and the derived lines carry either 4Ai-2 or a part of it. Two (CI17881, CI17886) were 4Ai 2 addition lines. CI17882 and CI17885 were 4Ai-2-(4D) substitution lines. CI17883 was a translocation substitution line with a pair of 6AL.4Ai-2S and a pair of 6AS.4Ai-2L chromosomes substituting for chromosome pairs 4D and 6A of wheat. CI17884 carried a 4DL.4Ai-2S translocation which substituted for chromosome 4D. CI17766 carried a 4AL.4Ai-2S translocation substituting for chromosome 4A. The results show that the 4Ai-2 chromosome is related to homoeologous group 4 and that the resistance gene(s) against WSMV is located on the short arm of 4Ai-2. In addition, CI17882, CI17884, and CI17885 contained Ae. speltoides chromosome 7S substituting for chromosome 7A of wheat. The greenbug resistance gene Gb5 was located on chromosome 7S. PMID- 24221270 TI - Restoration of normal stamen development and pollen formation by fusion of different cytoplasmic male-sterile cultivars of Nicotiana tabacum. AB - Fusion of two cytoplasmic male-sterile cultivars of Nicotiana tabacum, one with N. bigelovii cytoplasm and one with N. undulata cytoplasm, resulted in the restoration of male fertility in cybrid plants. All male-fertile cybrids exhibited fused corollas, which is characteristic for the cultivar with N. undulata cytoplasm, while their stamen structures varied from cybrid to cybrid, some producing stamens with anthers fused to petal-like appendages and one producing stamens of a normal appearance for N. tabacum. Restriction enzyme digestion and agarose gel electrophoresis of mitochondrial DNA showed that mitochondrial DNA of the fertile cybrids was more similar to the male-sterile cultivar with the cytoplasm of N. undulata than to the cultivar with N. bigelovii cytoplasm. Some restriction fragments were unique to the male-fertile cybrids. Comparisons between stamen structure and mitochondrial DNA for eight fertile progeny from one cybrid plant led to the identification of several restriction fragments that appeared at enhanced levels in connection with normal stamen development. PMID- 24221271 TI - A chromosome-specific DNA sequence which reveals a high level of RFLP in wheat. AB - An unusual genomic DNA clone, PSR454, was isolated from a partial genomic library of wheat. This sequence is moderately repeated and detects at least 30 related sequences, all located in a tight linkage block on the long arm of chromosome 3B. When used as a RFLP probe, PSR454 detects a high level of polymorphism between wheat varieties that carry the sequence. There is no detectable hybridisation to sequences in one-third of the varieties tested, providing an "on-off" polymorphism that can be detected on dot blots, rather than the more resource consuming conventional Southern analysis. PMID- 24221272 TI - Influence of wheat and rye parents on agronomic characters in primary hexaploid and octoploid triticale. AB - Thirty-five hexaploid and twenty octoploid primary triticales (xTriticosecale Wittmack) derived from homozygous wheat and rye inbred lines were used (1) to investigate the parental wheat, rye, and interaction effects and (2) to estimate quantitative genetic parameters for agronomic traits. The winter triticales were tested in four environments in a three-replicate split-plot design with drilled 1 m(2) plots. Superior performance of hexaploid triticales as compared to the octoploids was revealed. Substantial genetic variation and high heritability estimates were found for nearly all of the characters investigated. Estimates of wheat, rye, and wheat*rye interaction variance components disclosed parental main effects to be the most important source of genetic variation in primary triticales. The rye parent was dominant for all characters affecting fertility, and the wheat parent was more important for vegetative development. Character correlations were very similar for triticales of both ploidy levels. The lack of association between grain yield and tillering and the positive correlation between kernels per spike and thousand kernel weight indicated physiological disorders specific for primary triticales. PMID- 24221273 TI - Gametic selection in anther culture of rice (Oryza sauva L.). AB - The segregation and recombination of heterozygous isozyme markers have been monitored in anther culture derivatives (i.e., six nonmorphogenic microspore derived callus [NMC] populations and two anther culture plant [ACP] populations) and F2 plants generated from six F1 hybrids of rice, including five japonica upland/improved indica tropical hybrids. The alleles in excess at some loci displaying skewed segregations in the F2s were consistently overrepresented in the NMC populations. These alleles were also generally found to be overabundant in the two ACP populations except for certain loci that contrastingly segregated in a 1?1 ratio. Additional distortions were found to be specific to AC derivatives indicating the existence of in vitro gametic selection. Overall, however, the gametic selection in the ACP materials was neutral with regard to the indica and japonica differentiation. Estimates of linkages between markers borne by chromosome 6 using AC-derivative data were consistent with those noted in the F2s and with current knowledge of the isozyme locus linkage map. Given the average neutrality of gametic selection and the consistency of linkage relationships in the ACPs, their further use as rice molecular mapping and gene tagging populations can be investigated with confidence. PMID- 24221274 TI - Linkage between isozyme markers and a locus affecting seed size in Phaseolus vulgaris L. AB - Backcross and F2 progenies were produced between two bean genotypes, 'XR-235' and 'Calima,' which differ in seed weight by a factor of two. The small-seeded 'XR 235' was used as the pistillate and recurrent parent. These genotypes showed polymorphisms at nine isozyme loci and at the phaseolin locus. Seed size parameters (weight, length, width, and thickness) were determined for each BC1 and F2 individual, i.e., for seeds harvested from 'XR-235' after pollination with F1 and from the F1 after selfing, respectively. A combination of starch gel electrophoresis and enzyme activity staining was used to determine the genotype of each BC1 and F2 individual at the segregating loci. SDS-PAGE and Coomassie blue staining were used to determine geno-type at the phaseolin locus. Tests for independent assortment using two-way contingency and maximum likelihood tables revealed three linkage pairs: Aco-1 - 20 cM - Dia-1; Adh-1 - 2 cM - Got-2; and Est-2 - 11 cM - Pha. Statistical comparisons were made between the means of genotype classes at each segregating locus for all seed size parameters. The results from two independently obtained BC1s and the F2 consistently indicated that the Adh-1-Got-2 segment was linked to a locus that affected seed size and overcame maternal control over seed size. This locus has been designated Ssz-1. This gene exhibited additive gene action and accounted for 30-50% of the seed size difference between the parents. PMID- 24221275 TI - Comparison of the organization of the mitochondrial genome in tomato somatic hybrids and cybrids. AB - The organization of the mitochondrial genome in somatic hybrids and cybrids regenerated following fusion of protoplasts from cultivated tomato, Lycopersicon esculentum, and the wild species, L. Pennellii, was compared to assess the role of the nuclear genotype on the inheritance of organellar genomes. No organellar encoded traits were required for the recorvery of either somatic hybrids or cybrids. The organization of the mitochondrial genome was characterized using Southern hybridization of restriction digestions of total DNA isolated from ten cybrids and ten somatic hybrids. A bank of cosmid clones carrying tomato mitochondrial DNA was used as probes, as well as a putative repeated sequence from L. pennellii mitchondrial DNA. The seven cosmids used to characterize the mitochondrial genomes are predicted to encompass at least 60% of the genome. The frequency of nonparental organizations of the mitochondrial genome was highest with a probe derived from a putative repeat element from the L. pennellii mitochondrial DNA. There was no difference in the average frequency of rearranged mitochondrial sequences in somatic hybrids (12%) versus cybrids (10%), although there were individual cybrids with a very high frequency of novel fragments (30%). The frequency of tomato-specific mtDNA sequences was higher in cybrids (25%) versus somatic hybrids (12%), suggesting a nuclear-cytoplasmic interaction on the inheritance of tomato mitochondrial sequences. PMID- 24221276 TI - Tracheostomy in adolescent patients bridged to lung transplantation with ambulatory venovenous extracorporeal membrane oxygenation. AB - Venovenous extracorporeal membrane oxygenation (VV-ECMO) is quickly becoming a method to bridge patients with advanced pulmonary disease to lung transplantation. Historically, pediatric hospitals have more in-depth experience with the use of ECMO; however, bridging children with this method of respiratory support to lung transplantation is carried out infrequently with limited reported experiences in the medical literature. This article describes the optimal use of ambulatory VV-ECMO in two adolescent patients who were bridged to lung transplantation aided by tracheostomy placement. PMID- 24221278 TI - A simple rapid photometric estimation of the growth response of immobilized cells to fusaric acid and gamma radiation. AB - A simple and rapid photometric method was developed in order to evaluate the growth responses of cells to various factors in vitro. Cells of Asparagus officinalis L. were mixed with autoclaved agar at 40 degrees C and 90 MUl drops were dispensed into several Petri dishes. After the drops solidified, they were covered with a liquid growth medium and incubated on a gyratory shaker. Growth was measured every 2 or 3 days by two methods. In the first, the agar drop was placed under a stereomicroscope with substage illumination and the light passing through the embedded cells was measured by a light-meter. Growth, expressed by the increase in cell density, was inversely proportional to the intensity of transmitted light. In the second method, the agar drop was melted in a microwave oven and the packed cell volume was measured. The correlation between the two methods showed that the photometric method can be used to assess growth response of immobilized cells, during the first two weeks of culture. This method was used to evaluate growth responses to the toxin fusaric acid and to gamma radiation. The photometric method requires a small amount of inoculum, standard microscopic equipment and can be used to determine the effect of various factors on the growth of intact plant cells in vitro without disruption. PMID- 24221277 TI - Surgical completeness of robotic thyroidectomy: a prospective comparison with conventional open thyroidectomy in papillary thyroid carcinoma patients. AB - BACKGROUND: Using the da Vinci((r)) robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients. MATERIALS AND METHODS: From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups. RESULTS: Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group. CONCLUSION: Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients. PMID- 24221279 TI - Histological comparison of single somatic embryos of maize from suspension culture with somatic embryos attached to callus cells. AB - An embryogenic suspension culture of Zea mays, genotype 4C1, was obtained from friable callus that was cultured on solid medium and had been obtained from zygotic embryos. The suspension contained non-dividing elongated cells, clusters of dividing isodiametric cells, and globular, ovoid, and polar stages of somatic embryos. The single somatic embryos were blocked in shoot meristem formation: when transferred to regeneration medium they developed a root and, at the shoot side, a green cap with meristematic cells, but a scutellum and leaf primordia were not formed. In medium containing 2,4-dichlorophenoxy acetic acid, somatic embryos formed embryogenic callus aggregates, consisting of globular stage somatic embryos attached to each other via undifferentiated callus cells. These somatic embryos developed into mature embryos with the zygotic histological characteristics, such as scutellum and leaf primordia, in maturation medium, and then regenerated into plants in regeneration medium. By omitting the maturation phase, regeneration occurred via organogenesis. Polyembryos, i. e. embryos attached to each other without callus tissue in between, behaved as single somatic embryos. It is concluded that the attached callus tissue provides a factor that stimulates scutellum and leaf primordia formation. PMID- 24221280 TI - Crown gall transformation of lentil (Lens culinaris Medik.) with virulent strains of Agrobacterium tumefaciens. AB - Four diverse strains of Agrobacterium tumefaciens (C58, Ach5, GV3111, and A281) were capable of inducing tumors at a high frequency on inoculated stems of lentil (Lens culinaris Medik. cultivar Laird) in vivo, and on excised shoot apices in vitro. GV3111 and Ach5 produced the largest and heaviest tumors in vivo, while A281 produced the heaviest tumors in vitro. Tumor formation and opine production are indicative of plant cell transformation and tumors produced appropriate opines: nopaline (C58), octopine (Ach5 and GV3111), and agropine and mannopine (A281). Southern analysis of DNA from a tumor line produced by strain C58 showed that a T-DNA fragment had been transferred into the lentil genome. PMID- 24221281 TI - Enhancement of berberine production by spermidine in Thalictrum minus cell suspension cultures. AB - Berberine production in cell suspension cultures of Thalictrum minus L. var. hypoleucum Miq. was significantly enhanced by administration of spermidine, whereas other polyamines such as cadaverine, putrescine and spermine were ineffective. The results of experiments indicated that spermidine causes an increase of ethylene generation which is closely associated with activation of berberine biosynthesis. PMID- 24221282 TI - Activity of 1,2-benzisoxazole-3-one and indole-2,3-dione on plant regeneration in vitro and on cell elongation. AB - We tested the morphogenetic and cell elongating activity of 1,2-benzisoxazole-3 one, a compound similar to 1,2-benzisoxazole-3-acetic acid but lacking the lateral carbon chain. For comparison, we tested also the activity of indole 2,3 dione, having the same indolic ring as indole 3-acetic acid but no lateral carbon chain. The tests were made on the regeneration of tomato (Lycopersicon esculentum Miller var. Alice) from cotyledons and on pea (Pisum sativum L. var. Alaska) stem elongation. We found that 1,2 benzisoxazole-3-one retains part of the high shoot inducing activity of 1,2-benzisoxazole-3-aceticacid, while indole-2,3-dione is inactive. Both compounds have no effect on root induction or cell elongation. It seems therefore that the activity of 1,2 benzisoxazole-3-acetic acid is partly related to the structure of its ring, and that also in this respect 1,2 benzisoxazole-3-acetic acid differs from other auxinlike compounds. PMID- 24221283 TI - In vitro morphogenetic response and distribution of endogenous plant hormones in hypocotyl segments of snapdragon (Antirrhinum majus L.). AB - Snapdragon seedlings, 20 mm in length, were cut into 5 segments from the cotyledon to the root, which were cultured in vitro on hormone-free MS medium. Adventitious shoot formation was highest in the basal hypocotyl segments with stimulation by the addition of BA. Endogenous cytokinins were higher in the basal hypocotyl segments than in the two upper hypocotyl segments, whereas auxin content was higher in the two upper than in the basal hypocotyl segments. Ratios of cytokinins to auxin were also the highest in the basal hypocotyl segment. A general principle in in vitro culture that a high concentration of cytokinin and a low concentration of auxin promotes the induction of shoot morphogenesis was confirmed from measurements of endogenous growth regulator concentrations. PMID- 24221284 TI - Identification of broccoli and cauliflower cultivars with RAPD markers. AB - RAPD (Random Amplified Polymorphic DNA) markers generated by 4 arbitrary 10-mer primers, discriminated 14 broccoli and 12 cauliflower cultivars (Brassica oleracea L.) by banding profiles. The size of the amplified DNA fragments ranged from 300 to 2600 base pairs. Twenty-eight percent of the markers were fixed in both broccoli and cauliflower, whereas 12.5% were specific to either crop. The rest were polymorphic in either or both crops. The markers generated by two and three primers were sufficient to distinguish each of the broccoli and cauliflower cultivars, respectively. The average difference in markers was 14.5 between broccoli and cauliflower markers, 5.8 between two broccoli cultivars and 7.9 between two cauliflower cultivars. Larger differences for each crop were found between cultivars from different seed companies than within the same company. RAPD markers provide a quick and reliable alternative to identify broccoli and cauliflower cultivars. PMID- 24221285 TI - Avocado fruit protoplasts: a cellular model system for ripening studies. AB - Mesocarp protoplasts were isolated from mature avocado fruits (Persea americana cv. Hass) at varying stages of propylene-induced ripening. Qualitative changes in the pattern of radiolabel incorporation into polypeptides were observed in cells derived from fruit at the different stages. Many of these differences correlate with those observed during radiolabeling of polypeptides from fresh tissue slices prepared from unripe and ripe fruit. Protoplasts isolated from fruit treated with propylene for one day or more were shown to synthesize cellulase (endo-beta-1,4 glucanase) antigen, similar to the intact propylene-treated fruit. These results suggest that the isolated protoplasts retain at least some biochemical characteristics of the parent tissue. The cells may also be used in transient gene expression assays. Protoplasts isolated from preclimacteric and climacteric fruit were equally competent in expressing a chimeric test gene, composed of the CaMV 35S RNA promoter fused to the bacterial chloramphenicol acetyltransferase gene, which was introduced by electroporation. PMID- 24221286 TI - Transient gene expression of microprojectile-introduced DNA in Douglas-fir cotyledons. AB - Plasmid DNA containing the reporter gene uidA encoding beta-glucuronidase (GUS), driven by the cauliflower mosaic virus 35S promoter, was introduced on high velocity microprojectiles into cultured cotyledons of Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco]. Transient gene expression was measured by counting the number of distinct loci of GUS activity per cotyledon. Contrary to published results on angiosperms, repeated bombardments did not increase expression in Douglas-fir. Expression varied significantly among cotyledons from different seedlings. The amount of time between DNA delivery and treatment of cotyledons with auxins and cytokinins strongly affected GUS expression. The optimal cytokinin pretreatment produced an average of 20 loci per cotyledon. In several experiments, more than 95% of the treated cotyledons exhibited at least some transient expression. Expression remained constant up to three days following DNA delivery into cotyledons. PMID- 24221287 TI - Mitochondrial DNA patterns are similar in gametosomatic and somatic hybrids of two Nicotiana species. AB - The segregation and recombination patterns of mitochondrial genome in the somatic hybrids of Nicotiana tabacum and N. rustica were studied by RFLP analysis using four heterologous mitochondrial DNA probes, namely cytochrome oxidase subunit I (COI), cytochrome oxidase subunit II (COII), 26s rDNA and 5s-18s rDNA. These RFLP patterns were compared with those of the gametosomatic hybrids of these two species. A preponderance of N. rustica type patterns was observed in the somatic hybrids. One of the somatic hybrids had N. rustica type pattern with COI probe, novel pattern with COII, and 26s rDNA probe and N. tabacum type pattern with 5s 18s rDNA probe. These patterns are identical to those of some of the gametosomatic hybrids and could only be due to the recombination of mitochondrial genomes of the two parents. The extent and the nature of recombination of mitochondrial genomes is similar in gametosomatic and somatic hybrids. PMID- 24221288 TI - Propagation of Costus speciosus (Koen.) Sm. through in vitro rhizome production. AB - Rhizomes developed in vitro on shoots of Costus speciosus (Koen.) Sm. which were initiated from zygotic embryos. The effect of different hormonal and nutritional additions to Schenk and Hildebrandt' s (SH) basal nutrient medium on rhizome development was studied. Rhizomes developed on SH basal salts but formed with increased frequency on medium supplemented with adenine sulfate, casamino acids (CA) and various combinations of cytokinins and auxins. Incubation in light was necessary for rhizome formation. Isolated basal as well as nodal (aerial) rhizomes formed and produced new shoots. In basal medium without any growth additives (control) the average number of shoots produced per inoculum was 3.3 +/ 0.73 whereas in the best suited medium i.e. supplemented with 250 mg l(-1) CA the number of shoots obtained was 22.7+/-1.92. There was no dormancy period for rhizomes under the cultural conditions investigated. Rhizome-sprouts were easily transplanted from the in vitro conditions to the field. More than five hundred propagules (i.e. sprouted-rhizomes) were obtained within 5 months and it has been estimated that more than 2.4 * 10(5) propagules could be achieved per year through four subsequent in vitro rhizomes-generation cycles. Thus, a rapid method of propagation has been established. PMID- 24221289 TI - Plant regeneration from embryogenic suspension cultures of oil palm (Elaeis guineensis Jacq.). AB - Suspension cultures of oil palm (Elaeis guineensis Jacq.) were established in a medium with 80 or 100 mg.l(-1) 2,4-dichlorophenoxyacetic acid and 1 g.l(-1) activated charcoal, from calli producing embryogenic cells and protruding proembryos. The suspension was composed of meristematic clumps, breaking away and giving rise to new smaller aggregates. Under the best conditions, the initial weight increased about 4 fold in one month. Embryo differentiation was achieved when plating the clumps either directly, or after a phase in hormone-free liquid medium. In the second case, early maturation occurred in liquid medium. Secondary embryogenesis was reduced, and up to 18.1 % embryos formed shoots. Rooted plants were sucessfully transferred to soil. PMID- 24221290 TI - The stability of foreign protein production in genetically modified plant cells. AB - The stability of foreign protein production in genetically engineered plant cells was studied. A cultured tobacco cell line was transformed with a chimeric molecule carrying a bacterial gene, beta-glucuronidase (GUS), under plant regulatory sequences. The specific GUS activity was monitored for 294 days with ten independently transformed cell lines either in the presence or the absence of selectable antibiotics. Specific GUS activity was stably maintained in five lines. About a two-to four-fold increase in the GUS activity was observed from three cell lines. The remaining two cell lines lost the activity within the first 70 to 210 days. The presence of antibiotics did not significantly alter the stability of the foreign protein production in all cell lines examined. PMID- 24221291 TI - Rice seed toxicity tests for organic and inorganic substances. AB - Plant seed toxicity tests can be used to evaluate hazardous waste sites and to assess toxicity of complex effluents and industrial chemicals. Conventional plant seed toxicity tests are performed using culture dishes containing filter paper. Some reports indicate that filter papers might interfere with the toxicity of inorganic substances. In this study, a plastic seed tray was used. Rice was used as the test species.A comparison of results in the literature and this study revealed that variation of test species, methods, exposure duration, and other factors may affect the test results. The results of this study showed that the order of decreasing toxicity of metal ions was Cu>Ag>Ni>Cd>Cr(VI)>Pb>Zn>Mn>NaF for rice. The test results were similar to those reported in the literature for lettuce Ag>Ni>Cd,Cu>Cr(VI)>Zn>Mn, millet Cu,Ni>Cd>Cr(VI)>Zn>Mn, and ryegrass Cu>Ni>Mn>>Pb>Cd>Zn>Al>Hg>Cr>Fe. The order of decreasing toxicity of organic herbicides was paraquat, 2,4-D>>glyphosate>bromacil. PMID- 24221292 TI - Comparative environmental threat analysis: Three case studies. AB - In comparative threat analysis, threats imposed by different environmental problems are measured and compared. This type of analysis can be used to assess the overall threat to the environment, and to identify the most serious threat ('key problem') and areas which are particularly threatened ('problem areas'). Fundamental to comparative threat analysis is a common yardstick by which stresses imposed by different environmental problems can be compared. Such a yardstick may be the carrying capacity of the environment for environmental loads.In this paper we review how carrying capacity for different environmental problems is operationalized. Next, we discuss whether it is possible to compare threats, using the exceeding of carrying capacity as a yardstick. We point out problems and uncertainties in such a comparative threat analysis using three case studies: threats to European groundwater resources; threats to ecosystems in Europe; and threats to ecosystems, human health and groundwater resources in the Netherlands. On the basis of the results we advocate the application of risk assessment to enhance methodological uniformity in assessing protection levels for different environmental problems. PMID- 24221293 TI - Optimum macrobenthic sampling protocol for detecting pollution impacts in the Southern California Bight. AB - The optimum macrobenthic sampling protocol [sampling unit, sieve mesh size, and sample size (n)] was determined for detecting ecologically important pollution impacts in the Southern California Bight, U.S.A. Cost, in laboratory processing time, was determined for samples obtained using fourteen sampling units (0.005 0.1 m(2) surface area) and two sieve mesh sizes (1.0 and 0.5 mm). Statistical power analyses for t-tests of means were performed to estimate the minimum sample size (n min) needed to reliably (alpha=0.05, 1-beta?0.95) reject the null hypothesis of no difference between a reference and both a stimulated and a degraded station on twelve measures of community structure. The optimum sampling protocol for detecting impacts was determined as that with the lowest total cost *n min on most measures.Five replicate, 0.02 m(2)*5 cm deep, 1.0 mm mesh samples per station could reliably distinguish reference from impacted conditions on nine or ten measures of community structure at less than one quarter of the cost of the standard sampling protocol of 5 replicate, 0.1 m(2), 1.0 mm mesh samples per station. About 5 replicate, small (<0.1 m(2)), 1.0 mm mesh samples per station may often be optimal for detecting important structural changes in macrobenthic communities with naturally high species richness and abundance. PMID- 24221294 TI - The effect of salinity, temperature and time on the accumulation and depuration of copper in ragworm, Hediste (Nereis) diversicolor (O.F. Muller). AB - Under a low temperature condition of 12 degrees C, accumulation of copper by the ragworm, Hediste (Nereis) diversicolor, increased at low salinity of 7.60/00 but was reduced at intermediate and high salinities of 15.25 and 30.50/00, respectively. Copper contents of the worms at low salinity and temperature ranged from 68 to 185 ug/g. Under increasing temperature of 17 and 22 degrees C, bioavailability of copper to the worms increased irrespective of salinity gradient. The copper contents of the worm ranged from 59 to 784 ug/g dry weight. ANOVA analysis of data showed that salinity did not significantly affect accumulation of copper by the worm. Temperature significantly affected accumulation. The interaction of salinity and temperature was significant and complex, and days of exposure did not influence accumulation. Depuration of copper by the worm was independent of salinity which ranged from 510 to 15.6 ug/g. Temperature significantly affected depuration. The interaction of salinity and temperature was significant. However, individual worms neither accumulated nor depurated at the same rate. PMID- 24221295 TI - Comparative spray drift studies of aerial and ground applications 1983-1985. AB - The amount of off-site pesticide spray drift from aerial and ground applications was determined at 26 sites across Ontario. These were conducted along transects, parallel and at right angles to the flight path during aerial spray applications and at right angles to the direction of ground spray applications. All sites monitored were where commercial spray operations were in progress. The aerial applications involved both fixed wing aircraft and helicopters and the ground applications involved concentrated air-blast machines and high and low pressure boom sprayers. Deposits of spray drift outside the target area were common to all spray equipment monitored. All except low-pressure boom spraying equipment resulted in measurable spray drift to 80 m off-target with appreciable deposits up to 30-40 m. In a forest spray operation, where insecticide release was the highest, measurable residues were found up to 120 m off-target. The amount of chemical deposited off-target varied with the chemical, the climatical conditions and the equipment used. With a low-pressure boom sprayer, serious drift was confined to 9 m off-target and measurable residues to 15 m. PMID- 24221296 TI - Cadmium and zinc source assessment in the Sepetiba Bay and basin region. AB - Industrial and weathering inputs of Cd and Zn to the Sepetiba Bay and basin were assessed, based on production parameters obtained from local environment and industry authorities, and literature data. The results are compared with similar evaluations from other coastal regions and field data obtained in measuring Zn and Cd transport by rivers, direct run-off and atmospheric deposition in the region. Cadmium and zinc inputs to the bay increased by three orders of magnitude relative to pre-industrial fluxes and presently reach up to 1.6 and 180 tonnes per year for Cd and Zn, respectively, which represents a large input-to-area ratio, and explains the high concentration of these metals previously reported in the estuarine biota and sediments of Sepetiba Bay. Industrial activities, mainly metallurgical and chemical, comprise 94% and 84% of the total Cd and Zn inputs to the Bay. This figure identifies the point sources as being responsible for the environmental contamination and for regional poisoning risks. PMID- 24221298 TI - Utilization of surface localized substrate by non-adhesive marine bacteria. AB - Thirty-four marine bacteria were isolated from the eluate of seawater passed through a column of glass beads coated with stearic acid. Irreversible attachment of these isolates to stearic acid-coated glass surfaces ranged from 7.6-100% of the total attached population, with 7 isolates exhibiting less than 10% irreversible adhesion. All 14 isolates tested were able to utilize surface bound(14)C-stearic acid, even though some showed mostly reversible adhesion to the surface. More detailed studies were made comparing the reversibly adheringVibrio MH3 with the irreversibly adheringPseudomonas NCMB2021. MH3 cells were readily removed from the surface by a gentle shear force, and a significant degree of(14)C-labeling of MH3 cells, but not of NCMB2021 cells, in the bulk phase was observed. The ecological significance of nutrient scavenging at solid surfaces by reversibly attached bacteria is considered. PMID- 24221299 TI - Variation of environmental features and microbial populations with salt concentrations in a multi-pond saltern. AB - A multi-pond saltern that creates a gradient of salt concentrations has been studied with respect to some characteristics of the resulting environments and their microbial populations. The increase in salt concentration was correlated with increase in diurnal temperature and biomass present and with decrease in oxygen concentrations. Many types of organisms below 15% (w/v) total salts, were found, many of them normal inhabitants of seawater and even freshwater. Most organisms over 15% salts were halophilic. The salt concentrations comprised two ranges, each characterized by different microbial populations. First, between 15 and 30% salts, the populations ofDunaliella increased, reaching large numbers; moderately halophilic eubacteria and some fast-growing halobacteria predominated as heterotrophic microorganisms and, among the first, thePseudomonas-Alteromonas Alcaligenes group andVibrio were the more abundant taxonomic groups; and gram positive cocci appeared mainly over 25% salts. Phototrophic bacteria, both oxygenic and anoxygenic, were also found in this range, and among the anoxygenic type,Chromatium species andRodospirillum salexigens were probably predominant. Second, over 30% salts the diversity decreased greatly, all organisms found at the lower salt concentrations disappeared, and instead large populations of halobacteria developed. Over 50% salts, only three species of halobacteria were found. PMID- 24221300 TI - Variability in fermentation patterns of sugar-utilizing bacteria isolated from anaerobic, intertidal sediments. AB - Three dominant types of sugar-fermenting bacteria were isolated from the anaerobic, intertidal sediments of the Eems-Dollard estuary by applying techniques involving anaerobic agar shake tubes. One of the isolated types was tentatively identified as aStreptococcus species, the other two asBacteroides species. All types were versatile with respect to the utilization of sugars. The fermentation patterns of two types were dependent upon conditions of cultivation. In glucose-limited cultures ofStreptococcus strain NS.G52, the production of lactate was suppressed in favor of formate, acetate, and ethanol. In glucose limited syntrophic cultures withMethanospirillum hungatei, Bacteroides strain NS.G42 was forced to produce acetate and hydrogen at the expense of ethanol. The fermentation pattern ofBacteroides strain NS.S42, which consisted of acetate, propionate, and succinate, was not affected by conditions of cultivation. PMID- 24221301 TI - Factors influencing hydrocarbon degradation in three freshwater lakes. AB - The mixed microbial flora of 3 lakes in Ohio with differing histories of hydrocarbon pollution was examined in relation to the ability to use hydrocarbons. Weathered kerosene was spiked with naphthalene, pristane, 1,13 tetradecadiene, andn-hexadecane and added to water-sediment mixtures from the 3 lakes, and utilization of the 4 marker hydrocarbons was measured. Each of the marker hydrocarbons was metabolized; naphthalene was the most readily used and pristane was the most resistant. Values for dissolved oxygen suggest that oxygen did not limit hydrocarbon degradation in the water column at any site examined. Nutrient addition studies indicated that nitrogen and phosphorus limited hydrocarbon degradation at all sites examined. Maximum numbers of heterotrophic bacteria were detected when the water temperature was 10 degrees C or higher. The data indicate that temperature limits hydrocarbon degradation in the winter, except at a site which had been impacted by an oil spill and which received chronic inputs of hydrocarbons and nutrients. In samples from that site, all 4 marker hydrocarbons were degraded at 0 degrees C. Results of temperature and nutrient-addition experiments suggest that different seasonal populations of hydrocarbon users are selected at that site, but not at other lake sites. PMID- 24221302 TI - Copper toxicity to cyanobacteria and its dependence on extracellular ligand concentration and degradation. AB - Copper toxicity to the cyanobacteriumPlectonema boryanum (UTEX 594) has been investigated in the presence of citrate and nitrilotriacetic acid (NTA) using a copper-saturated culture medium. The coppercitrate complex was biodegradable, and toxicity was dependent on the free ligand concentration. The ratio of citrate to copper also affected the extent of metal toxicity. NTA was not degraded byP. boryanum. Ligand degradation in the cyanobacterial culture increased the ionic copper concentration and caused a concomitant reduction in growth. The ecological implications of these findings are discussed. PMID- 24221303 TI - Antibiotic activity of epiphytic bacteria isolated from intertidal seaweeds. AB - A survey of antibiotic-producing bacteria from the microbial flora attached to seaweeds and the study of their antibiotic capacities were carried out. From 5 species of green and brown marine algae, 224 bacterial strains were isolated and tested for antibiotic production. A total of 38 strains displayed antibiotic activity, withEnteromorpha intestinalis being the source of the highest number of producer strains. All epiphytic bacteria with antibiotic activity were assigned to thePseudomonas-Alteromonas group. Antagonism assays among the isolates demonstrated that each producer strain inhibits the growth of the other producers, as well as of some nonproducer strains also isolated from seaweeds. Likewise, an autoinhibitory effect was observed in all antibiotic-producing strains. Antibacterial spectra of all the strains include activity againstStaphylococcus, Alcaligenes, Pseudomonas, Vibrio, Pasteurella, andAchromobacter. A preliminary characterization of the antibiotic substances produced by these epiphytic bacteria demonstrated that they are low molecular weight compounds, thermolabile, and anionic and are not affected by proteolytic enzymes. The role that these inhibitory substances can play in the natural environment is discussed. PMID- 24221297 TI - The far side of auxin signaling: fundamental cellular activities and their contribution to a defined growth response in plants. AB - Recent years have provided us with spectacular insights into the biology of the plant hormone auxin, leaving the impression of a highly versatile molecule involved in virtually every aspect of plant development. A combination of genetics, biochemistry, and cell biology has established auxin signaling pathways, leading to the identification of two distinct modes of auxin perception and downstream regulatory cascades. Major targets of these signaling modules are components of the polar auxin transport machinery, mediating directional distribution of the phytohormone throughout the plant body, and decisively affecting plant development. Alterations in auxin transport, metabolism, or signaling that occur as a result of intrinsic as well as environmental stimuli, control adjustments in morphogenetic programs, giving rise to defined growth responses attributed to the activity of the phytohormone. Some of the results obtained from the analysis of auxin, however, do not fit coherently into a picture of highly specific signaling events, but rather suggest mutual interactions between auxin and fundamental cellular pathways, like the control of intracellular protein sorting or translation. Crosstalk between auxin and these basic determinants of cellular activity and how they might shape auxin effects in the control of morphogenesis are the subject of this review. PMID- 24221304 TI - Analysis of the community structure of yeasts associated with the decaying stems of cactus. III.Stenocereus thurberi. AB - Yeast communities in necroses of organpipe cactus (Stenocereus thurberi) were surveyed at 3 localities in Arizona. Quantitative analysis of random samples allows comparisons of the types and numbers of yeasts at 3 levels: within plants, between plants within a locality, and between localities. The analysis shows that the major source of variability is between plants. This pattern is identical with the pattern shown by agria cactus (Stenocereus gummosus) and is thought to be due to sampling different successional stages. No significant differences in estimates of the effective number of yeast species (ENS) in agria and organpipe samples were found. Comparisons of agria, organpipe, and prickly pear (Opuntia) cacti support the hypothesis that cactus chemistry is an important determinant of the yeast community structure which, in turn, is an important determinant of the diversity ofDrosophila species which utilize necrotic cacti as feeding and breeding substrates. PMID- 24221305 TI - Interaction of competing fungi with fly larvae. AB - Saprophytic fungi have degradative abilities and interspecific interactions which suggest that resource use and yield should increase as species number increases, but previous studies show the opposite. As a test of the possibility that invertebrate activity changes fungal resource use patterns, we grew coprophilous fungi on rabbit feces at the same initial density singly or in mixtures of 2, 4, or 6 species, with or without activity of larvalLycoriella mali (Diptera: Sciaridae). Fungi in mixtures without larvae caused less weight loss in one mixture, and greater weight loss in 2 mixtures than when growing alone; fungi in 4 of 6 mixtures produced fewer spores than when growing alone. Overall, without larvae, weight loss did not increase as number of fungal species increased. Larvae did not change the pattern of weight loss or proportions of spores caused by mixing fungal species. Numbers of larvae surviving to pupate rose as fungal species numbers increased; as a result, weight loss increased with fungal species number in cultures with larvae. PMID- 24221307 TI - Analysis of genetic control of mating behavior in screwworm (Diptera: Calliphoridae) males through diallel crosses and artificial selection. AB - The mode of genetic control of male screw-worm (Diptera: Calliphoridae) mating behavior was examined using diallel cross and artificial selection. Diallel crosses showed strong dominance effects, with hybrids being uniformly more successful in copulation than their more inbred parental strains. Weaker additive and reciprocal effects were also noted. Environmental (replicate) effects were highly significant. Regression of array variances and covariances indicated that epistatic interactions or unequal allele distribution during gametogenesis may have occurred and that high courtship propensity polygenes show dominance over low propensity genes. Artificial selection on males from outbred strains from Guatemala and Belize resulted in a decreased number of mating attempts for lines selected for reduced activity, but mating attempts in lines selected for high mating activity did not increase. A combination of inbreeding during the selection cycles as well as selection for recessive traits would explain this response. The two types of experiments were in general agreement, indicating significant dominance and environmental influence on male mating behavior with weaker additive and possible maternal effects. PMID- 24221306 TI - Interventions against nutrient-sensing pathways represent an emerging new therapeutic approach for diabetic nephropathy. AB - Autophagy has evolved as a stress response that allows unicellular eukaryotic organisms to survive in starved conditions by regulating energy homeostasis and/or by protein and organelle quality control. The diabetes-induced accumulation of damaged proteins and organelles results in the development and progression of diabetic nephropathy. In contrast, autophagy machinery is activated by calorie restriction and environmental stress in proximal tubular cells, and is maintained at a high level in podocytes, suggesting its crucial role in the pathogenesis of diabetic nephropathy. However, its role in diabetic nephropathy has not been fully known. Here, we will discuss the role of autophagy and its involvement in the pathogenesis of diabetic nephropathy. PMID- 24221308 TI - Stable transformation of barley via PEG-induced direct DNA uptake into protoplasts. AB - Protoplasts isolated from a barley cell suspension (cv Dissa) were transformed with plasmid DNA containing the neomycinphosphotransferase II (NPT) and beta glucuronidase (GUS) genes, using polyethyleneglycol (PEG) to induce DNA uptake. Transformed microcalli were selected in media containing G418 sulphate. NPT activity was detected in all antibiotic-resistant cell lines, but not all NPT positive cell lines had GUS activity. Southern analysis confirmed the presence of sequences homologous to the APT and GUS genes in DNA of G418-resistant callus. PMID- 24221309 TI - Photosynthetic performance in wild emmer wheat, Triticum dicoccoides: ecological and genetic predictability. AB - In a twin study, we have shown that wild emmer wheat, Triticum dicoccoides, the progenitor of all cultivated wheats, harbours important genetic variation (Vg) in photosynthetic characteristics. This Vg resides within and between populations and ecogeographical regions in Israel, which is the center of origin and diversity of wild emmer wheat. Here we analyzed, by univariate and multivariate methods, the significant differentiation of variation in photosynthetic characteristics of 107 genotypes from 27 populations of wild emmer in Israel, distributed in three ecogeographical regions including central, xeric (northern cold and eastern warm) marginal, and mesic (western) marginal populations. The highest photosynthetic efficiency was displayed by populations of the xeric marginal region, but most variation for photosynthetic capacity occurs between accessions within ecogeographical regions and populations. Genotypes and populations of T. dicoccoides having high photosynthetic capacity can be identified by climatic factors and isozyme markers. The identification by genetic markers, if substantiated by testcrosses, can facilitate the maximization of conservation, in situ or ex situ, and utilization of these photosynthetic genetic resources for improvement of hexaploid wheat (T. aestivum). PMID- 24221310 TI - Intraspecific variation of chloroplast DNA in Dioscorea bulbifera L. AB - Restriction fragment length polymorphism (RFLP) analysis of chloroplast (ct) DNAs from 15 accessions of Dioscorea bulbifera collected from Africa and Asia was carried out using the Southern hybridization technique. Eight cloned ctDNA fragments of D. bulbifera and D. opposita, which cover 80% of the total chloroplast genome, were used as the probes to detect variation in ctDNA digested with nine restriction endonucleases. Ten variable sites, located in the large and small single-copy regions, were disclosed among the 15 accessions, of which six showed base substitution and four carried length mutation. Positions of the latter mutations were determined on the physical map of ctDNA. Based on these results, chloroplast genomes of the 15 accessions could be classified into nine types. Their phylogenetic relationships are assumed to be as follows: (1) African and Asian chloroplast genomes diverged from each other at the earliest point in time; (2) E-type chloroplast genome, occurring in the south-east edge of the Asian continent, appears to be the most ancient among all the Asian chloroplast genomes; and (3) four chloroplast genomes, found in Asian insular regions, are probably derived independently from the E-type genome. The discrepancy between the taxonomic relationship and the proposed chloroplast genome phylogeny of the present materials is noted. PMID- 24221311 TI - Tagging genes for blast resistance in rice via linkage to RFLP markers. AB - Both Pi-2(t) and Pi-4(t) genes of rice confer complete resistance to the blast fungal pathogen Pyricularia oryzae Cav. As economically important plant genes, they have been recently characterized phenotypically, yet nothing is known about their classical linkage associations and gene products. We report here the isolation of DNA markers closely linked to these blast resistance genes in rice. The DNA markers were identified by testing 142 mapped rice genomic clones as hybridization probes against Southern blots, consisting of DNA from pairs of nearly isogenic lines (NILs) with or without the target genes. Chromosomal segments introgressed from donor genomes were distinguished by restriction fragment length polymorphisms (RFLPs) between the NILs. Linkage associations of the clones with Pi-2(t) and Pi4(t) were verified using F3 segregating populations of known blast reaction. Cosegregation of the resistant genotype and donor derived allele indicated the presence of linkage between the DNA marker and a blast resistance gene. RFLP analysis showed that Pi-2(t) is closely linked to a single-copy DNA clone RG64 on chromosome 6, with a distance of 2.8+1.4(SE) cMorgans. Another blast resistance gene, Pi-4(t), is 15.3+4.2(SE) cMorgans away from a DNA clone RG869 on chromosome 12. These chromosomal regions can now be examined with additional markers to define the precise locations of Pi-2(t) and Pi-4(t). Tightly linked DNA markers may facilitate early selection for blast resistance genes in breeding programs. These markers may also be useful to map new genes for resistance to blast isolates. They may ultimately lead to the cloning of those genes via chromosome walking. The gene tagging approach demonstrated in this paper may apply to other genes of interest for both monogenic and polygenic traits. PMID- 24221312 TI - Organelle transfer by microfusion of defined protoplast-cytoplast pairs. AB - Defined cybridization was performed by one-to-one electrofusion (microfusion) of preselected protoplast-cytoplast pairs of male-fertile, streptomycin-resistant Nicotiana tabacum and cytoplasmic male-sterile, streptomycin-sensitive N. tabacum cms (N. bigelovii), followed by microculture of the fusion products until plant regeneration. Dominant selectable markers, namely, kanamycin resistance (nptII) and hygromycin B resistance (hpt) genes had been previously integrated in the nuclear genomes of the otherwise almost fully isogenic parental strains using direct gene transfer to protoplasts. In addition to chromosome counts indicating the expected allotetraploid tobacco count of 48, the absence of the nucleus from the cytoplast donor line was confirmed by Southern blot hybridization using nptII and hpt probes, as well as by an in vitro selection test with leaf expiants and the corresponding enzyme assays for 30 cybrids. The cytoplasmic composition of the cybrids obtained was analyzed for chloroplast type using the streptomycin resistance/sensitivity locus. The fate of mitochondria in cybrids was checked by species-specific patterns in Southern analysis of restriction endonuclease digests of total DNA with N. sylvestris mitochondrial DNA probes. PMID- 24221313 TI - The inheritance of genetic markers in microspore-derived plants of barley Hordeum vulgare L. AB - Biochemical, molecular and morphological markers have been used to monitor the segregation of alleles at major gene loci in microspore-derived lines of four spring barley crosses and their parents. Significant deviations from the expected Mendelian ratios were observed for four of the ten markers studied in the cross. Distorted ratios were associated with loci located on chromosomes 4H and 6H. The differential transmission of alleles was in favour of the responsive parent (Blenheim) used in the anther culture studies. For the alpha-Amy-1 locus on chromosome 6H, the preferential transmission of Blenheim alleles was most pronounced in the haploid regenerants that were colchicine treated. These results are discussed in relation to the genetic control of androgenetic response in barley and with respect to the exploitation of another culture in barley improvement. PMID- 24221314 TI - A general approach for the study of a population of testcross progenies and consequences for recurrent selection. AB - A model to study genetic effects at the level of a population of testcross progenies is presented. As there is no dominance for the testcross value, with the restriction of epistasis to pairs of loci, only additive x additive epistasis can contribute to the variance among progenies. To estimate the variance among progenies due to epistasis, it is necessary to have the population structured in families of full sibs, half sibs or S1, with only a few plants per family tested in combination with the tester. Using a two-way mating design to produce the families, it is possible to estimate the variance due to additive x additive epistasis. The consequence of the presence of epistasis is studied at the level of recurrent selection for combining ability with the tester. It seems that epistasis itself does not change the efficiency of the breeding methods considered. However, when the population from intercrossing is structured in families, it could be efficient to use a combined selection when the heritability is very low. In this case it would be efficient to produce full-sib families (by single-pair matings) at the level of intercrossing. The best procedure is to produce such families at the same time as crossing with the tester. In comparison to the classical scheme of selection for combining ability with a tester, such a modification increases the efficiency of selection 41.1% if an off-season generation can be used. PMID- 24221315 TI - Estimation of preferential pairing in tetraploid x diploid hybridizations. AB - Crosses made between tetraploid and diploid, 2n pollen-producing species directly transfer from one-half to the entire diploid genome from the diploid to the tetraploid level, depending on the mechanism of 2n pollen formation and the amount of crossing-over that occurs. Tetraploid plants that result from tetraploid x diploid hybridizations can be further utilized in a breeding program. It is postulated that preferential pairing between homologous chromosomes derived from the original tetraploid or diploid parent occurs in the tetraploid x diploid hybrid. Depending on the genetic divergence of the species involved, preferential pairing of homologous chromosomes may range from zero to one. Theoretical estimates of the amount of preferential pairing and the standard errors of these estimates are derived for cases where the diploid parent produces 2n gametes by either a first division or a second division restitution mechanism. PMID- 24221316 TI - Regeneration of intergeneric somatic hybrid plants between Lycopersicon esculentum and Solanum muricatum. AB - Mesophyll protoplasts of tomato (Lycopersicon esculentum) and pepino (Solanum muricatum) were fused by using an electrofusion method and cultured in modified MS medium supplemented with naphthaleneacetic acid and kinetin, in which only pepino and somatic hybrid protoplasts could divide. Somatic hybrid plants showing intermediate characteristics in morphology were regenerated from the calli exhibiting vigorous growth in contrast with those of pepino. The hybrid nature of these plants was confirmed by cytological observation and biochemical analyses of phosphoglucomutase isozymes and the fraction-1-protein. The regenerated somatic hybrids grew to flowering stage and set fruits. PMID- 24221317 TI - Recovery of normal photosynthesis and respiration in common wheat with Agropyron cytoplasms by telocentric Agropyron chromosomes. AB - Alloplasmic common wheat (Triticum aestivum L. cultivais 'Penjamo 62' and 'Siete Cerros 66') with cytoplasms of wheatgrass (Agropyron trichophorum and Ag. glaucum) showed two aberrant phenotypes, i.e., gross reduction in plant vigor and male sterility. Plant vigor and male fertility were restored by cytoplasm specific telocentric chromosomes (telosomes). Studies on carbon assimilation and consumption and on oxygen evolution and uptake showed that maximum rates of apparent photosynthesis were significantly lower in the alloplasmic lines than in their corresponding euplasmic lines and that the telosomes restored a normal level of photosynthesis. The decreased apparent photosynthetic rates in the alloplasmic lines were shown to be not due to decreased rates of true photosynthesis but to increased rates of dark respiration in the green leaves. In contrast, dark respiration in the roots was significantly low in the alloplasmic lines. The alloplasmic lines also showed decreased rates of respiratory consumption of new photosynthates. These results suggest that growth depression and male sterility in the alloplasmic lines are related to aberrant mitochondrial function, which is compensated for by cytoplasm-specific telosomes. PMID- 24221318 TI - Determination of the transmission frequency of chromosome 4S (l) of Aegilops sharonensis in a range of wheat genetic backgrounds. AB - The transmission of chromosome 4S (l) from Aegilops sharonensis was observed in a range of wheat genetic backgrounds. Chromosome 4S (l) was transmitted at a very high frequency (at least 97.8%) in all crosses. The genetic background appears to only have a small effect on transmission. The frequency of transmission of chromosome 4S (l) was the same in each genetic background through both the male and female gametes. PMID- 24221319 TI - Cytogenetic studies of the intergeneric hybrids between Secale cereale and Elymus caninus, E. brevipes, and E. tsukushiensis (Triticeae: Poaceae). AB - Integeneric hybridizations were carried out between Secale cereale L. (2n = 14, RR) and three Elymus species, namely, E. caninus (L.) L. (2n = 28, SSHH), E. brevipes (Keng) Love (2n = 28, SSYY) and E. tsukushiensis Honda (2n = 42, SSHHYY). Chromosome pairing was studied at metaphase I in the parental species and the hybrids. Meiotic configurations of the hybrids were 20.74 1+0.14 II for E. caninus x S. cereale (SHR), 16.35 I+2.17 II+0.09 III for E. brevipes x S. cereale (SYR) and 25.84 I+1.10 II+0.02 III for E. tsukushiensis x S. cereale (SHYR), in addition to some secondary associations in the different hybrids. It is concluded from the study that (1) a certain, different homoeologous relationship exists among "S", "H" and "Y" genomes in the investigated Elymus species; (2) low homoeology is present between genomes of Elymus (S or H or Y) and rye (R); (3) the Secale genome affects homoeologous chromosome pairing between different genomes in E. brevipes and E. tsukushiensis. PMID- 24221320 TI - Plastid DNA diversity in natural populations of Beta maritima showing additional variation in sexual phenotype and mitochondrial DNA. AB - Plants of two natural populations of Beta maritima, characterized by high percentages of male-sterile plants, have been investigated for organelle DNA polymorphism. We confirm the two classes of mitochondrial DNA variation previously described: (i) mitochondrial DNA (mtDNA) type N is associated with male fertility, whereas mtDNA type S can cause cytoplasmic male sterility (CMS); (ii) the 10.4-kb linear plasmid is observed in both types of mitochondria and is not correlated with the cytoplasmic male sterility occurring in this plant material. A third polymorphism is now described for chloroplast DNA (ctDNA). This polymorphism occurs within single populations of Beta maritima. Three different ctDNA types have been identified by HindIII restriction analysis. Among the plants studied, ctDNA type 1 is associated with N mitochondria and type 2 with S mitochondria. Chloroplast DNA type 3 has been found both in a fertile N plant and in a sterile S plant. This finding suggests that the chloroplast DNA polymorphism reported is not involved in the expression of male sterility. A comparison with Beta vulgaris indicates that ctDNA type 3 of Beta maritima corresponds to the ctDNA of fertile sugar beet maintainer lines. The three types of Beta maritima ctDNA described in this study differ from the ctDNA of male-sterile sugar beet. PMID- 24221321 TI - Inheritance of morphological and chemical characters in interspecific hybrids between Papaver bracteatum and Papaver pseudo-orientale. AB - The alkaloid profiles and morphological traits of the capsules of Papaver bracteatum, P. pseudo-orientale, and their hybrids were studied. Dominance of the hexaploid parent P. pseudo-orientale was observed for various characters. A genetic model assuming allelic additive effects and polysomic inheritance was elaborated for the control of isothebaine content in the capsules. The distribution of thebaine content in the segregating generations, F2 and BCF1 was evidence of the transfer of genes from the diploid parent P. bracteatum in the gametes of the interspecific hybrid and their expression in its progenies. These findings indicate the potential use of inter-specific hybrids between the Oxytona species in the breeding of cultivars for industrial or ornamental purposes. PMID- 24221322 TI - Relative family performance and variance structure of open-pollinated Douglas-fir seedlings grown in three competitive environments. AB - Open-pollinated Douglas-fir (Pseudotsuga menziesii var 'menziesii' (Mirb.) Franco) families were tested in three contrasting competitive environments to test the hypothesis that relative performance as measured by total seedling dry weight is dependent upon distance or genotype of neighbors. The three competitive environmnts included (1) a mixture of individuals from all families planted at close spacing, (2) single (pure) family blocks planted at close spacing, and (3) individuals from all families planted at a wide, non-competitive spacing. Despite occasional large changes in rank between competitive environments and only moderate correlations of family means between competitive environments, the family x competitive environment interaction was non-significant. Furthermore, families did not differ significantly in competitive ability or density tolerance. The competitive environment in which seedlings were grown, however, had a large effect on estimates of variance components, which in turn led to large differences in estimates of heritability and genetic gain. Evaluation of families in mixture resulted in the largest estimates of heritability, while evaluation in pure family blocks resulted in the lowest. Analysis of correlated response to selection indicated that testing and selection in mixture result in the largest estimated gain, even if progeny of selected individuals are subsequently grown in a pure or non-competitive environment. PMID- 24221323 TI - Cytological analysis on the distribution and origin of the alien chromosome pair conferring blue aleurone color in several European common wheat (Triticum aestivum L.) strains. AB - Meiotic chromosome pairing and Giemsa C-banding analyses in crosses of several European blue-grained wheat strains with Chinese Spring double ditelosomic and other aneuploid lines showed that Triticum aestivum Blaukorn strains "Berlin," "Probstdorf," "Tschermak," and "Weihenstephan" are chromosome substitutions, in which the complete wheat chromosome 4A pair is replaced, whereas the strains "Brunn" and "Moskau" are 4B substitutions. The alien chromosome pair in all of these strains is an A genome chromosome (4A) from diploid Triticum monococcum or T. boeoticum not present in common tetraploid and hexaploid cultivated wheats. The Blaukorn strain Weihenstephan "W 70a86" possesses, in addition to a rye chromosome pair 5R compensating for the loss of part of chromosome 5D, a 4A/5DL translocation replacing chromosome pair 4B of wheat. PMID- 24221324 TI - Weighted regression analysis for comparing varietal adaptation. AB - The normally used joint linear regression analysis (OLS) is not appropriate for comparing estimates of stability parameters of varieties when the error variances of site means are heterogeneous. Weighted regression analysis (WLS), in these situations, yields more precise estimates of stability parameters. A comparison of the two analytical methods using the grain yield (kg ha(-1)) data of 12 varieties and one hybrid of pearl millet [Pennisetum typhoides (Burm.) S. & H.], tested at 26 sites in India, revealed that the weighted regression analysis yields more efficient estimates of regression coefficients (b i ) than the ordinary regression analysis, and that the standard errors of b i values were reduced by up to 43%. The estimated b i differed with the two procedures. The number of varieties with b i ssignificantly deviating from unity was not only more (five varieties) with weighted regression analysis than the ordinary regression analysis (one variety), but the classification of varieties as possessing general or specific adaptation differed with the two procedures. PMID- 24221325 TI - Effect of fungal homogenate, enzyme inhibitors and osmotic stress on alkaloid content of Catharanthus roseus cell suspension cultures. AB - The addition of Aspergillus niger homogenate to Catharanthus roseus cell suspension cultures produced an increment of more than 60% in the alkaloid content of two different cell lines. The use of an inhibitor of phenylalanine ammonia lyase, i. e. cinnamic acid, along with the homogenate, resulted in an appearance of 90% of the alkaloids in the medium. Furthermore, even in the absence of fungal homogenate, there was a marked increase in the alkaloid content. The exposure of the cells to an osmotic stress produced a marked increment (320%) in the total alkaloid content. When both stress treatments were applied sequentially, an additive effect on alkaloid accumulation was observed. It was 300% higher than in cells cultured without treatment, the majority of the alkaloids found in the medium. PMID- 24221326 TI - The influence of jasmonic acid on biophysical properties of potato leaf protoplasts and roots. AB - Jasmonic acid (JA) and its derivatives are a novel group of plant endogenous growth regulators. In our experiments some new data about the physiological effects of JA were obtained using electron paramagnetic resonance spectroscopy. Experiments were performed on potato plants (Solanum tuberosum L. cv. Vesna) grown in vitro. Different quantities of JA (0.1-10 MUM) were added to the growth medium. Root samples of plants grown on media supplemented with JA showed a more rapid spin probe N-oxyl-2,2,6,6-tetramethyl piperidine reduction than the control plants, which is a possible indicator of altered root permeability. Samples of leaf protoplasts were probed with methyl ester of 5-doxyl-haxadecanoic acid. We observed a membrane fluidity decrease in protoplasts isolated from plants grown on higher concentrations of JA (1 and 10 MUM). PMID- 24221327 TI - Induction of virulence response in Agrobacterium tumefaciens by tissue explants of various plant species. AB - Forty-four plant species belonging to different taxa were tested for their ability to induce the expression of the virulence E gene in Agrobacterium tumefaciens containing virE:lacZ fusion constructs. With the exception of 6 algae, one fern and 2 monocots, tissue explants of all other plants (2 Algae, 3 Bryophytes, 2 Pteridophytes, 15 Gymnosperms, 8 Monocots and 5 Dicots) induced the expression of the virE gene as detected by the presence of beta-galactosidase activity in the bacteria. PMID- 24221328 TI - Evidence for the occurrence of polyamine oxidase in the dicotyledonous plant Medicago sativa L. (alfalfa). AB - Polyamine oxidase (EC 1.5.3.3) activity has not been detected previously in cells of dicotyledonous plants, although it has been characterized extensively in monocotyledonous plants. Evidence is presented in this report for the occurrence of polyamine oxidase in dialyzed crude extracts of the dicotyledonous plant, Medicago sativa L. (alfalfa). Three enzyme assays were used to quantitate the formation of the three products of the reaction catalyzed by polyamine oxidase. 1 Pyrroline formation was measured colorimetrically as a yellow quinazolinium complex with o-aminobenzaldehyde. Hydrogen peroxide formation was measured spectrophotometrically with a coupled peroxidase assay system by peroxidative oxidation of guaiacol. [(3)H]1,3-Diaminopropane formation was measured by using [1,8-(3)H]spermidine as the substrate and separating the radiolabelled reaction product from the substrate by paper electrophoresis. This latter assay provided evidence that a polyamine oxidase of type [EC 1.5.3.3] catalyzed the cleavage reaction between a secondary nitrogen atom and an adjacent carbon of the butyl moiety of spermidine. Significant polyamine oxidase activity was detected in floral tissues, cortex tissues of the root, young leaves, and young germinated seedlings of alfalfa. The occurrence of polyamine oxidase in alfalfa accounts for the formation of the essential substrate, 1,3-diaminopropane, required for the biosynthesis of the uncommon polyamines, norspermidine and norspermine, which we have recently detected in alfalfa. PMID- 24221329 TI - Patterns of transformation intensity on flax hypocotyls inoculated with Agrobacterium tumefaciens. AB - Cellular transformation intensities on flax (Linum usitatissimum) hypocotyl explants using disarmed Agrobacterium tumefaciens were investigated through various preculture durations, cocultivation durations and removal of epidermis. The expression of an intron-containing beta-glucuronidase (GUS) gene driven by CaMV 35S promoter served as a reporter for determination of transformed tissues on hypocotyls. The binary plasmid p35SGUSINT in octopine-type Agrobacterium strain GV2260 was used as the vector system. A prolonged cocultivation duration (5-7 days) resulted in a much higher transformation staining intensity (frequency * tissue area) than 2- or 3-day-cocultivation duration on hypocotyls variously precultured prior to inoculation. A high staining intensity on the two cut ends was obtained from nonprecultured hypocotyls. A reduction in intensity on the upper cut end of hypocotyls was observed with preculture times greater than 6 days. Peeled hypocotyls with a post-peeling preculture of 2 or 3 days had a high proportion of superficial area covered by transformed tissues after a 7 day cocultivation duration. These results will help to improve the efficiency of recovery of transgenic plants by increasing the proportion of transformation in the regenerable tissues. PMID- 24221330 TI - Characterization of salt tolerant alfalfa (Medicago sativa L.) plants regenerated from salt tolerant cell lines. AB - Salt tolerant cell lines have been selected from Medicago sativa, by a single step selection process on tissue culture medium containing 1% NaCl. Plants regenerated from these lines show improved salt tolerance compared to parent plants. The regenerated plants are vigorous, have flowered and are self fertile. The cellular salt tolerance characteristic can be passaged through the regenerated plants, since callus cultures initiated from immature ovaries of the salt tolerant regenerated plants are salt tolerant without additional selection on 1% NaCl. Several of these "second generation" callus cultures have been regenerated to produce vigorous plants which maintain the salt tolerance characteristic. The tolerance phenotype appears dominant in seeds obtained from self fertilization of the tolerant plants. The regenerated salt tolerant plants are therefore a valuable source as genotypes in plant breeding for salt tolerance and isolation, identification and manipulation of genes which confer salt tolerance in alfalfa. PMID- 24221331 TI - Embryo culture of Costus speciosus (Koen.) Sm. to regenerate variable diosgenin yielding clones. AB - Mature embryos of Costus speciosus were excised and cultured on Schenk and Hildebrandt's (1972) nutrient medium containing auxins and cytokinins either alone or in combination. Multiple shoots were obtained when kinetin and indole-3 butyric acid were supplemented each at 0.1 mg 1(-1) concentration. Embryo-derived plantlets were multiplied through propagation of rhizomes and the propagules derived from a single embryo were designated as an embryoclone. Twenty such embryo-clones were maintained in the field. Variations in rhizome biomass yield and diosgenin contents of these embryoclones were noted. Thirty-six percent of the embryo-clones studied were high diosgenin yielding types. Diosgenin contents at the intraclonal level were uniform. The in vitro raised plants were morphologically uniform and indistinguishable from their parent. PMID- 24221332 TI - In vitro high frequency plant regeneration of a tree legume Tamarindus indica (L.). AB - Optimal culture conditions for high frequency plant regeneration from excised cotyledons of Tamarindus indica were established. Maximum shoot bud differentiation (100%) occurred when the adaxial surface of the entire cotyledon (excised from 12-d old seedlings) was in contact with MS medium containing 5*10( 6)M BAP. On MS alone only roots were formed. Shoot or root formation was confined to nodal tissue at the top of the notch present on the adaxial surface at the proximal end of the cotyledon. Thirty-four to 95 shoots were regenerated in a 4 month period from individual cotyledons. Shoots were rooted on MS with 5.7*10( 6)M IAA. IAA (5.7*10(-7)M) alone induced complete plant formation. Regenerated plants were established in the soil with 70% success. PMID- 24221333 TI - High frequency production of haploid embryos in asparagus anther culture. AB - A method for obtaining a high frequency of haploid asparagus embryos through anther culture was developed. Flowers collected from plants in the field in July, August and September 1990, for the genotype G203, were stored at 5 degrees C for 24 h. Anthers were placed on Murashige and Skoog medium (MS) containing 500 mg l (-1) casein hydrolysate, 800 mg l(-1) glutamine, 2 mg l (-1) NAA, 1 mg l (-1) BA and 5 % sucrose at 32 degrees C in the dark for three to four weeks to induce calli. Calli were then grown at 25 degrees C with a 16 h photoperiod for three to four weeks. Developing embryos and calli were transferred to embryo maturation medium, MS containing 6% sucrose, 0.1 mg l (-1) NAA, 0.1 mg l (-1) kinetin and 0.65 mg l (-1) ancymidol, for four weeks. More than 50% of the recovered mature embryos germinated on MS containing l mg l (-1) GA3. Anthers with microspores at the late-uninucleate stage had the highest frequency of total and embryogenic calli formation, 40% and 15%, respectively. Each embryogenic callus usually produced 10-15 embryos. Aproximately 75 plants per 100 anthers cultured were recovered: 76% haploid, 22% diploid and 2% triploid. High temperature was critical for the induction of embryogenic callus. PMID- 24221334 TI - Reduction of 2,3,5-triphenyltetrazolium chloride by the KCN-insensitive, salicylhydroxamic acid-sensitive alternative respiratory pathway of mitochondria from cultured grapevine cells. AB - The reduction of 2,3,5-triphenyltetrazolium chloride (TTC) by grapevine cells cultured in suspension was studied in order to assess the reliability of using TTC reduction as a measure of cell viability. Similar to the reduction observed in animals cells, TTC can be reduced in grapevine cells by the cytochrome respiratory path of the mitochondria, although it is mostly reduced (about 72 %) by the alternative respiratory path sensitive to salicylhydroxamic acid. Engagement of the alternative path in TTC reduction was calculated through the ?Valt plot, and was established to be 89 %. PMID- 24221335 TI - Culture medium pH is influenced by basal medium, carbohydrate source, gelling agent, activated charcoal, and medium storage method. AB - When four carbohydrates were tested against six commonly cited inorganic basal media, post-autoclave pH was highest for carbohydrate-free and sucrose containing media, and progressively lower for maltoseglucose and fructose-containing media, respectively. Post-autoclave pH for these media without carbohydrates was related to medium buffering capacity. Addition of gelling agents (10 of 11 tested) increased the postautoclave pH of MS medium containing sucrose. Neutralized and acid-washed activated charcoal also increased the post-autoclave pH of liquid and agarsolidified MS medium, and the pH changed further during 8 weeks of storage. Changes in medium pH caused by gelling agents, but not charcoal, could be alleviated by adjusting the pH after their addition but prior to autoclaving. PMID- 24221336 TI - Phenylacetic acid-induced somatic embryogenesis in cultured hypocotyl explants of geranium (Pelargonium x hortorum Bailey). AB - The effect of a non-indole compound, phenylacetic acid (PAA), on the induction of somatic embryogenesis in tissue cultures of geranium (Pelargonium x hortorum Bailey cv. Scarlet Orbit Improved) was investigated. Hypocotyl explants derived from young, dark-grown seedlings were cultured on Murashige and Skoog (1962) medium (MS) supplemented with PAA or IAA (0.01-120 MUM) alone or in combination with BAP (8 MUM). Somatic embryogenesis was induced by both PAA and IAA at 0.01 20 MUM with 8 MUM BAP, however, the optima differed considerably for the two compounds. Maximal activity of IAA for somatic embryogenesis was found at 0.1-2.5 MUM, whereas PAA gave best results at 10 and 20 MUM under identical culture conditions. Higher concentrations (30-120 MUM) of IAA or PAA in the medium induced callusing in the explants, but the callus was neither embryogenic nor morphogenic. PMID- 24221337 TI - Plant regeneration from callus-derived protoplasts of Pelargonium x domesticum. PMID- 24221338 TI - Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer. AB - BACKGROUND AND AIM: miR-21, a putative tumor oncomiR, is a frequently overexpressed miRNA in a variety of tumors. Because it targets tumor-suppressor genes it has been linked to tumor progression. In this study we investigated the role of miR-21 in esophageal squamous cell carcinoma (ESCC), and its possible mechanism. METHODS: Expression of miR-21 was detected by stem-loop RT-PCR in tissue from 76 invasive ESCC at stage I-IV and in their corresponding para cancerous histological normal tissues (PCHNT). Thirty endoscopic esophageal mucosal biopsy specimens from non-tumor patients were used as controls. Expression of PTEN in 76 paired ESCC and PCHNT was investigated by real-time RT PCR and an immunohistochemical method, respectively. Paired tumor and PCHNT specimens of 20 ESCC cases were randomly selected for western blot analysis. The effect of miR-21 on PTEN expression was assessed in the ESCC cell line with an miR-21 inhibitor to reduce miR-21 expression. Furthermore, the roles of miR-21 in cell biology were analyzed by use of miR-21 inhibitor-transfected cells. RESULTS: Stem-loop RT-PCR revealed miR-21 was significantly overexpressed in ESCC tissues and cell lines. Overexpression of miR-21 correlated with tumor status, lymph node metastasis, and clinical stage. We demonstrated that knockdown of miR-21 significantly increased expression of PTEN protein. Consequent PTEN expression reduced cell proliferation, invasion, and migration. CONCLUSIONS: Our findings suggest that miR-21 could be a potential oncomiR, probably by regulation of PTEN, and a novel prognostic factor for ESCC patients. PMID- 24221339 TI - ERCP: the unresolved question of endotracheal intubation. AB - The anesthesia community is still divided as to the appropriate airway management in patients undergoing endoscopic retrograde cholangiopancreatography. Increasingly, gastroenterologists are comfortable with deep sedation (normally propofol) without endotracheal intubation. There are no comprehensive reviews addressing the various pros and cons of an un-intubated airway management. It is hoped that the present review will benefit both anesthesia providers and gastroenterologists. The reasons to avoid routine endotracheal intubation and the approaches for an un-intubated anesthetic management are discussed. The special situations where endotracheal intubation is the preferred approach are mentioned. Many special techniques to manage airway are illustrated. PMID- 24221340 TI - A causal relationship between cough and gastroesophageal reflux disease (GERD) has been established: a pro/con debate. AB - Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of nonacid or weakly acidic reflux. Further contributing to the controversy are recent studies that demonstrate that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The fourth American Cough Conference (New York, June 2013) provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough. PMID- 24221341 TI - Staging of acute exacerbation in patients with idiopathic pulmonary fibrosis. AB - BACKGROUND: The purpose of this study was to evaluate the predictors of a 3-month mortality rate of acute exacerbation of idiopathic pulmonary fibrosis (IPF) and provide a new staging system. METHODS: A total of 594 patients with IPF were included in this retrospective, observational study conducted from January 2001 to December 2010 at Okinawa Chubu Hospital. RESULTS: Among the 594 patients, 58 (9.8 %) developed acute exacerbation (AE) of IPF during the 10-year observation period. The median follow-up period for AE was 10.4 months. In-hospital mortality was 56.9 % and the 3-month mortality rate was 63.8 %. We identified the following four parameters in a multivariate analysis as: serum lactate dehydrogenase, sialylated carbohydrate antigen (KL-6), ratio of partial pressure of oxygen and fraction of inspiratory oxygen, and total extent of abnormal findings on high resolution computed tomography of the chest. Patients were divided into two groups on the basis of the four composite parameters. Patients in the extensive disease-stage group required more mechanical ventilation and intensive therapy than those in the limited disease-stage group. The 3-month mortality rate was higher in patients in the extensive disease-stage group than in patients in the limited disease-stage group (80.6 vs. 54.5 %, respectively; p = 0.007). CONCLUSIONS: Staging of AE in patients with IPF provided useful information regarding disease severity and short-term outcome. PMID- 24221344 TI - Reliability of differing densities of sample grids used for the monitoring of forest condition in Europe. AB - Concern about the possible deterioration of forest health led to the establishment in the 1980s of inventories of forest condition throughout Europe. International standardisation of the programmes was sought and a number of recommendations were made concerning sampling and assessment procedures. One of the most important rulings was that the assessment should be made on a systematic grid, the minimum density of which was 16*16 km. However, many countries adopted denser sampling grids, with 4*4 km being used in several countries and 1*1 km being used in the Netherlands. With five or more years of monitoring completed, there is a growing belief that a rapid and irreversible decline in forest health is not occurring. Consequently, some countries/regions are seeking to reduce their annual investment in forest health monitoring.The precision of national/regional estimates of forest health can be directly related to the sample size. As the sample size decreases, so also does the precision of the estimates. This is illustrated using data collected in Switzerland in 1992 and using grid densities of 4*4 km, 8*8 km, 12*12 km and 16*16 km. The value of the data is dependent on the sample size and the degree to which it is broken down (by region or species). The loss of precision associated with most subdivisions at the 8*8 km grid level remains acceptable, but a sharp deterioration in the precision occurs at the 12*12 km and 16*16 km grid levels. This has considerable implications for the interpretation of the inventories from those countries using a 16*16 km grid. In Switzerland, a reduction from the current 4*4 km grid to an 8*8 km grid (i.e. 75% reduction in sample size) would have relatively little impact on the overall results from the annual inventories of forest health. PMID- 24221343 TI - Increased Toll-like receptor 5 expression indicates esophageal columnar dysplasia. AB - Toll-like receptor 5 (TLR5) is an immune receptor, which recognizes bacterial flagellin. Increased expression has been reported in various premalignant and malignant lesions indicating a role in carcinogenesis. We assessed the expression of TLR5 in normal esophageal squamous epithelium, Barrett's esophagus with and without dysplasia, and in esophageal adenocarcinoma. Specimens with normal esophagus (n=93), gastric (n=75) or intestinal metaplasia (n=53) without dysplasia, and low-grade (n=56) or high-grade dysplasia (n=33) and esophageal adenocarcinoma (n=94) were studied. TLR5 immunohistochemical stainings were analyzed for the proportion of positive cells and the intensity of expression. In normal squamous epithelium, only the basal third showed TLR5 expression. In esophageal gastric or intestinal metaplasia, expression was present in majority of the cells but significantly weaker (p<0.001) than in dysplastic epithelium. In dysplasia, expression extended to the apical cytoplasm, contrasting basolateral expression in non-dysplastic columnar epithelium. Receiver operating characteristic curve analysis showed that moderate to high expression intensity of TLR5 indicates low-grade dysplasia with 86 % sensitivity and 83 % specificity. Carcinomas showed increased expression in comparison with non-dysplastic columnar epithelium, but there was no association with prognosis. Our results indicate that the esophageal columnar dysplasia is associated with clear increase of TLR5 expression and dissolution of regular polarized expression. TLR5 staining provides a possible biomarker for the recognition of low-grade dysplasia. In addition, the findings suggest a role for abnormal expression of TLR5 in the pathogenesis of esophageal adenocarcinoma and suggest importance of altered microbiome in the pathogenesis of complications of Barrett's esophagus. PMID- 24221342 TI - Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology. AB - This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenocarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy. PMID- 24221345 TI - Ammonia uptake by plants. AB - The paper considers the methodology and results of experimental determination of dry deposition and ammonia uptake by isolated plant leaves. Analytical expressions are proposed which allow a transition from rates obtained in an isolated chamber to dry ammonia deposition by standing crops leaves. PMID- 24221346 TI - Geographical distribution of organochlorine contaminants and reproductive parameters in Herring Gulls on Lake Superior in 1983. AB - As part of the Great Lakes International Surveillance Plan, 1978-83, egg contaminant levels and reproductive output were determined for Herring Gull colonies on Lake Superior in 1983. Since 1974, the Herring Gull has been widely used in the Great Lakes as a spatial and temporal monitor of organochlorine (OC) contaminant levels and associated biological effects. Most eggs contained a wide range of OCs, the main compounds being DDE, polychlorinated biphenyls (PCBs), dieldrin, heptachlor epoxide, oxychlordane, hexachlorobenzene and mirex. Levels of an additional ten OCs and five polychlorinated dibenzo-p-dioxin (PCDD) congeners were also determined for some sites. Overall, levels varied significantly among colonies, but there was no obvious relationship to spatial distribution of contaminants in sediments or fish species. OC levels in eggs had declined by up to 84% since 1974. Eggshells were only 8% thinner than before the introduction of DDT, and shell thinning was not a cause of breeding failure. Average reproductive output varied from 0.15 to 1.57 young per apparently occupied nest in 1983: at 56% of colonies the value was below that thought necessary to maintain stable populations. The main causes of failure were egg disappearence and cannibalism of chicks. Despite this, the population appeared to have been increasing at about 4% per annum. Reduced availability of forage fish during the early 1980s was the most likely reason for the poor reproductive output in 1983. PMID- 24221347 TI - Notes on the dynamics and decomposition of leaves in a Nothofagus pumilio forest. AB - A research project was conducted in a native forest of Nothofagus pumilio in one of the southernmost Chilean Nation Parks, Torres del Paine, to check the amount and timing of leaf fall, their decomposition rate and the respiration rate of the soil on an annual cycle.This paper also provides the results of the decay of fallen leaves in time, the loss curve of leaf weights, the evolution of water content and records of the larger taxonomic groups of microarthropods associated with the decomposition of the material. PMID- 24221348 TI - Lead in hawks, falcons and owls downstream from a mining site on the Coeur d'Alene River, Idaho. AB - Mining and smelting at Kellogg-Smelterville, Idaho, resulted in high concentrations of lead in Coeur d'Alene (CDA) River sediments and the floodplain downstream, where American Kestrels (Falco sparverius), Northern Harriers (Circus cyaneus), Red-tailed Hawks (Buteo jamaicensis), Great Horned Owls (Bubo virginianus), and Western Screech-owls (Otus kennicotti) nested. Nestling American Kestrels contained significantly higher (P=0.0012) blood lead concentrations along the CDA River (0.24 ug/g, wet wt) than the nearby reference area (0.087 ug/g). A 35% inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) in nestling Northern Harriers (P=0.0001), 55% in nestling American Kestrels (P=0.0001) and 81% in adult American Kestrels (P=0.0004) provided additional evidence of lead exposure in the CDA River population. In nestling American Kestrels and Northern Harriers, ALAD activity was negatively correlated with lead in blood. An earlier report on Ospreys (Pandion haliaetus) showed slightly less inhibition of ALAD than in American Kestrels, but no significant reduction in hemoglobin or hematocrit and no negative influence on production rates. The adult and nestling American Kestrels along the CDA River contained about twice as much blood lead as Ospreys during the same years (adult 0.46 vs. 0.20 ug/g, and nestling 0.24 vs. 0.09 ug/g), but adults showed a 7.5% reduction in hemoglobin (P=0.0356) and nestlings an 8.2% reduction in hemoglobin (P=0.0353) and a 5.8% reduction in hematocrit (P=0.0482). We did not observe raptor deaths related to lead, and although the production rate for American Kestrels was slightly lower along the CDA River, we found no significant negative relation between productivity and lead. Limited data on the other raptors provide evidence of exposure to lead along the CDA River. Several traits of raptors apparently reduce their potential for accumulating critical levels of lead which is primarily stored in bones of prey species. PMID- 24221349 TI - Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation. AB - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab. CASE DIAGNOSIS/TREATMENT: An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence. CONCLUSION: Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis. PMID- 24221351 TI - Incorporation of post-translational modified amino acids as an approach to increase both chemical and biological diversity of conotoxins and conopeptides. AB - Bioactive peptides from Conus venom contain a natural abundance of post translational modifications that affect their chemical diversity, structural stability, and neuroactive properties. These modifications have continually presented hurdles in their identification and characterization. Early endeavors in their analysis relied on classical biochemical techniques that have led to the progressive development and use of novel proteomic-based approaches. The critical importance of these post-translationally modified amino acids and their specific assignment cannot be understated, having impact on their folding, pharmacological selectivity, and potency. Such modifications at an amino acid level may also provide additional insight into the advancement of conopeptide drugs in the quest for precise pharmacological targeting. To achieve this end, a concerted effort between the classical and novel approaches is needed to completely elucidate the role of post-translational modifications in conopeptide structure and dynamics. This paper provides a reflection in the advancements observed in dealing with numerous and multiple post-translationally modified amino acids within conotoxins and conopeptides and provides a summary of the current techniques used in their identification. PMID- 24221350 TI - Experimental renal progenitor cells: repairing and recreating kidneys? AB - Strategies to facilitate repair or generate new nephrons are exciting prospects for acute and chronic human renal disease. Repair of kidney injury involves not just local mechanisms but also mobilisation of progenitor/stem cells from intrarenal niches, including papillary, tubular and glomerular locations. Diverse markers characterise these unique cells, often including CD24 and CD133. Extrarenal stem cells may also contribute to repair, with proposed roles in secreting growth factors, transfer of microvesicles and exosomes and immune modulation. Creating new nephrons from stem cells is beginning to look feasible in mice in which kidneys can be dissociated into single cells and will then generate mature renal structures when recombined. The next step is to identify the correct human markers for progenitor cells from the fetus or mature kidney with similar potential to form new kidneys. Intriguingly, development can continue in vivo: whole foetal kidneys and recombined organs engraft, develop a blood supply and grow when xenotransplanted, and there are new advances in decellularised scaffolds to promote differentiation. This is an exciting time for human kidney repair and regeneration. Many of the approaches and techniques are in their infancy and based on animal rather than human work, but there is a rapid pace of discovery, and we predict that therapies based on advances in this field will come into clinical practice in the next decade. PMID- 24221352 TI - Underestimated contribution of skeletal muscle in ornithine metabolism during mouse postnatal development. AB - Ornithine aminotransferase (L-ornithine 2-oxoacid aminotransferase, OAT) is widely expressed in organs, but studies in mice have focused primarily on the intestine, kidney and liver because of the high OAT-specific activity in these tissues. This study aimed to investigate OAT activity in adult mouse tissues to assess the potential contribution to ornithine metabolism and to determine OAT control during postnatal development. OAT activity was widely distributed in mouse tissues. Sexual dimorphism was observed for most tissues in adults, with greater activity in females than in males. The contribution of skeletal muscles to total OAT activity (34% in males and 27% in females) was the greatest (50%) of the investigated tissues in pre-weaned mice and was similar to that of the liver in adults. OAT activity was found to be regulated in a tissue-specific manner during postnatal development in parallel with large changes in the plasma testosterone and corticosterone levels. After weaning, OAT activity markedly increased in the liver but dropped in the skeletal muscle and adipose tissue. Anticipating weaning for 3 days led to an earlier reduction of OAT activity in skeletal muscles. Orchidectomy in adults decreased OAT activity in the liver but increased it in skeletal muscle and adipose tissue. We concluded that the contribution of skeletal muscle to mouse ornithine metabolism may have been underestimated. The regulation of OAT in skeletal muscles differs from that in the liver. The present findings suggest important and tissue-specific metabolic roles for OAT during postnatal development in mice. PMID- 24221353 TI - Proline-glutamate chimera's side chain conformation directs the type of beta hairpin structure. AB - Our aim was to study the impact of two proline chimeras, containing a glutamic acid side chain in cis- or trans-configuration, on secondary structure formation. We further investigated to what extent the configuration of the side chain contributes to the overall peptide conformation. We used a 10 residue peptide (IYSNPDGTWT) that forms a beta-hairpin in water. The turn-forming proline was substituted with either a cis- or trans-proline-glutamic acid chimera, resulting in the peptides IYSNPcis -E DGTWT (P1_Pcis-E) and IYSNP(trans-E)DGTWT (P1_Ptrans E). We studied the conformation of the modified peptides by circular dichroism (CD) and NMR-spectroscopy, and SEC/static light scattering (SLS) analysis. NMR analysis reveals that the modified peptides maintain the beta-hairpin conformation in aqueous solution. At 5 degrees C and pH 4.3, the peptide (P1_Pcis-E) was found to adopt two coexisting beta-hairpin conformations (2:2 beta-hairpin, and 3:5 beta-hairpin). In contrast to that, the peptide (P1_Ptrans E) adopts a 2:2 beta-hairpin that exists in equilibrium with a 4:4 beta-hairpin conformation. The adoption of ordered beta-hairpin structures for both modified peptides could be confirmed by CD spectroscopy, while SEC/SLS analysis showed a monomeric oligomerization state for all three investigated peptides. With the combination of several NMR methods, we were able to elucidate that even small alterations in the side chain conformation of the proline-glutamate chimera (cis or trans) can significantly influence the conformation of the adopted beta hairpin. PMID- 24221354 TI - Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets. AB - This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets. PMID- 24221355 TI - Bacterial killing mechanism of sheep myeloid antimicrobial peptide-18 (SMAP-18) and its Trp-substituted analog with improved cell selectivity and reduced mammalian cell toxicity. AB - To develop short antimicrobial peptide with improved cell selectivity and reduced mammalian cell toxicity compared to sheep myeloid antimicrobial peptide-29 (SMAP 29) and elucidate the possible mechanisms responsible for their antimicrobial action, we synthesized a N-terminal 18-residue peptide amide (SMAP-18) from SMAP 29 and its Trp-substituted analog (SMAP-18-W). Due to their reduced hemolytic activity and retained antimicrobial activity, SMAP-18 and SMAP-18-W showed higher cell selectivity than SMAP-29. In addition, SMAP-18 and SMAP-18-W had no cytotoxicity against three different mammalian cells such as RAW 264.7, NIH-3T3 and HeLa cells even at 100 MUM. These results suggest that SMAP-18 and SMAP-18-W have potential for future development as novel therapeutic antimicrobial agent. Unlike SMAP-29, SMAP-18 and SMAP-18-W showed relatively weak ability to induce dye leakage from bacterial membrane-mimicking liposomes, N-phenyl-1-napthylamine (NPN) uptake and o-nitrophenyl-beta-galactoside (ONPG) hydrolysis. Similar to SMAP-29, SMAP-18-W led to a significant membrane depolarization (> 80%) against Staphylococcus aureus at 2 * MIC. In contrast, SMAP-18 did not cause any membrane depolarization even at 4 * MIC. In confocal laser scanning microscopy, we observed translocation of SMAP-18 across the membrane in a non-membrane disruptive manner. SMAP-29 and SMAP-18-W were unable to translocate the bacterial membrane. Collectively, we propose here that SMAP-29 and SMAP-18-W kill microorganisms by disrupting/perturbing the lipid bilayer and forming pore/ion channels on bacterial cell membranes, respectively. In contrast, SMAP-18 may kill bacteria via intracellular-targeting mechanism. PMID- 24221356 TI - Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models. AB - We recently proposed that the transient receptor potential melastatin 5 (TRPM5) cation channel contributes to glucose-induced electrical activity of the beta cell and positively influences glucose-induced insulin release and glucose homeostasis. In this study, we investigated Trpm5 expression and function in pancreatic islets from mouse models of type II diabetes. Gene expression analysis revealed a strong reduction of Trpm5 mRNA levels in pancreatic islets of db/db and ob/ob mice. The glucose-induced Ca(2+) oscillation pattern in db/db and ob/ob islets mimicked those of Trpm5 (-/-) islets. Leptin treatment of ob/ob mice not only reversed the diabetic phenotype seen in these mice but also upregulated Trpm5 expression. Leptin treatment had no additional effect on Trpm5 expression levels when plasma insulin levels were comparable to those of the vehicle injected control group. In murine beta cell line, MIN6, insulin downregulated TRPM5 expression in a dose-dependent manner, unlike glucose or leptin. In conclusion, our data show that increased plasma insulin levels downregulate TRPM5 expression in pancreatic islets from leptin-deficient mouse models of type 2 diabetes. PMID- 24221357 TI - Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle. AB - Skeletal muscle regulates substrate choice according to demand and availability and pyruvate dehydrogenase (PDH) is central in this regulation. Circulating interleukin (IL)-6 increases during exercise and IL-6 has been suggested to increase whole body fat oxidation. Furthermore, IL-6 has been reported to increase AMP-activated protein kinase (AMPK) phosphorylation and AMPK suggested to regulate PDHa activity. Together, this suggests that IL-6 may be involved in regulating PDH. The aim of this study was to investigate the effect of a single injection of IL-6 on PDH regulation in skeletal muscle in fed and fasted mice. Fed and 16-18 h fasted mice were injected with either 3 ng . g(-1) recombinant mouse IL-6 or PBS as control. Fasting markedly reduced plasma glucose, muscle glycogen, muscle PDHa activity, as well as increased PDK4 mRNA and protein content in skeletal muscle. IL-6 injection did not affect plasma glucose or muscle glycogen, but increased AMPK and ACC phosphorylation and tended to decrease p38 protein content in skeletal muscle in fasted mice. In addition IL-6 injection reduced PDHa activity in fed mice and increased PDHa activity in fasted mice without significant changes in PDH-E1alpha phosphorylation or PDP1 and PDK4 mRNA and protein content. The present findings suggest that IL-6 contributes to regulating the PDHa activity and hence carbohydrate oxidation, but the metabolic state of the muscle seems to determine the outcome of this regulation. In addition, AMPK and p38 may contribute to the IL-6-mediated PDH regulation in the fasted state. PMID- 24221359 TI - Method for measuring microbial degradation and mineralization of(14)C-labeled chitin obtained from the blue crab,Callinectes sapidus. AB - A method for measuring microbial degradation and mineralization of radiolabeled native chitin is described.(14)C-labeled chitin was synthesized in vivo by injecting shed blue crabs (Callinectes sapidus) with N-acetyl-D-[1-(14)C] glucosamine and allowing for its incorporation into the exoskeleton. The cuticle had a total organic carbon content of 0.48 mg C mg(-1) with a specific radioactivity of 6,356 CPM mg(-1). Glucosamine, i.e., chitin content as determined colorimetrically, was 22% (w/w). Microbial degradation and mineralization rates were assessed in batch culture using(14)C-chitin as substrate and York River water as inoculum. Replicate flasks were sampled daily for enumeration of chitinoclastic bacteria and the radiolabel recovered as particulate(14)C-chitin or(14)CO2. The amount of(14)CO2 generated was directly proportional to the loss of particulate(14)C-chitin, with 96% of the added label recovered as the sum of both phases. The maximum rate of mineralization was 207 mg day(-1) g(-1) seeded(14)C-chitin at 20 degrees C. Highest chitinoclastic bacterial counts corresponded to the period of maximum rate of chitinolysis. It is suggested that the rate of chitin mineralization is limited by exoenzymatic depolymerization and not by chitin concentration. PMID- 24221360 TI - Influence of phagotrophic processes on the regeneration of nutrients in two-stage continuous culture systems. AB - Regeneration of nutrients in aquatic ecosystems may be affected by autolysis, bacterial degradation, and activities of phagotrophic organisms. To examine the relative importance of these processes, mineralization of carbon, nitrogen, and phosphorus was studied in a two-stage continuous culture system. In the first stage (production compartment), aChlorella sp. was grown either axenically or in the presence of bacteria under P-limited conditions. In the presence of bacteria, the biomass of algae decreased due to efficient competition for P by bacteria. In the second stage (remineralization compartment), which was kept continuously in the dark, the nutrients incorporated by the organisms in the first stage were remineralized only slightly (0-25%) irrespective of the presence or absence of bacteria. However, remineralization of all nutrients tested was strongly increased (60-80%) after addition of zooflagellates, which grazed on algae and bacteria. These observations suggest that a net regeneration of nutrients was provided by phagotrophic organisms, whereas nutrients were trapped rather than released by bacteria. It is concluded that nutrient cycling could probably not proceed at the high velocities observed in the field without the participation of phagotrophic organisms. PMID- 24221358 TI - Saturated fatty acids up-regulate COX-2 expression in prostate epithelial cells via toll-like receptor 4/NF-kappaB signaling. AB - Cyclooxygenase-2 (COX-2) has been implicated in prostate carcinogenesis, and recently it has been confirmed to be a molecular target of saturated fatty acids (SFAs). In the present study, we investigated the effect of stearic acid (SA) and palmitic acid (PA), two of the most abundant SFAs contained in dietary fat, on COX-2 expression in prostate epithelial cells and the signaling transduction pathway involved. First, we demonstrated that both SA and PA increased the mRNA and protein expression of COX-2, and consistently induced the activation of NF kappaB in RWPE-1, BPH-1 and PC-3 prostate epithelial cell lines. The effect of SA and PA on COX-2 over-expression and NF-kappaB activation was in a dose-dependent manner, and PA was more potent than SA at the same concentration. Then, we demonstrated inhibition of NF-kappaB using its specific inhibitor strikingly attenuated PA-induced COX-2 expression. Toll-like receptor 4 (TLR4) was revealed to be expressed on RWPE-1, BPH-1 and PC-3 cell lines by PCR and immunofluorescence staining, and blocking its signaling significantly inhibited PA induced COX-2 over-expression and NF-kappaB activation. Taken together, we demonstrated that SFAs can up-regulate COX-2 expression in prostate epithelial cells, and this effect was mediated mainly through the TLR4/NF-kappaB signaling pathway. PMID- 24221361 TI - Physiological characterization of heterotrophic bacterial communities from selected aquatic environments. AB - Three different biotopes, groundwater, surface water, and activated sludge, were examined and the total colony count on nutrient agar determined. The bacteria that could be isolated from the agar plates were identified and their in vitro activities investigated. Three principal approaches were used: (1) isolates were identified and the results used in a numerical analysis to determine their similarity; (2) the different physiological properties of isolates originating from a single biotope were compiled and used to characterize the community (collective total activity); and (3) the diversity of the physiological properties of the isolates of all populations was determined; on the basis of main characters a "heterotrophic" diversity index was calculated. The possibility of using a polyphasic ecological study to characterize aquatic bacterial communities is considered. PMID- 24221362 TI - The bacterial biota on crustose (nonarticulated) coralline algae from Tasmanian waters. AB - The bacterial biota associated with the cuticle surface of healthy benthic samples of crustose nonarticulated coralline algae from the east coast of Tasmania (Australia) was examined by bacteriological cultivation and electron microscopy. In 32 samples studied, the viable count on Zobell's marine agar (supplemented with vitamins) was 3.3*10(6) bacteria g(-1) wet wt. (range 2.9*10(4)-2.7*10(7)). Of 732 strains isolated from 16 out of 32 samples and identified to genus level,Moraxella was the predominant genus (66%). In contrast,Moraxella comprised only 11% of 217 strains isolated from benthic seawater samples collected at the same time as coralline algae. In 22 out of 32 algal samples examined by scanning electron microscopy, the total count was 1.6 * 10(7) bacteria g(-1) wet wt. (range 5.1* 10(6)-3.8*107); the major morphotype was cocco-bacilli (80%). Several environmental factors did not significantly influence the viable count or generic distribution, or the total count or morphotypic distribution of bacteria on the cuticle. These factors included geographical site, season, storage of samples in aquarium conditions, and the presence or absence of abalone from shells that the coralline algae encrusted. The microbiota, consisting mostly of the nonmotile bacterial genusMoraxella, appeared to be highly adapted to its calcerous plant host. PMID- 24221363 TI - A numerical analysis of counts of diatom frustules, and other algae, in water samples from the River Wey. AB - During May 1978, samples of water were collected from 24 sites on, or associated with, the River Wey between its source south of Haslemere and Send just downstream of Guildford (approx. 57.5 km). Counts of diatom frustules, and other algae surviving the sampling technique, were analyzed by numerical taxonomic techniques. On the basis of community structure, the river was clearly separated into two regions. The seven sites along the first 18 km formed a cluster, and those of the remaining stretch formed a second cluster, which was more similar to Broadwater, a large shallow pond that discharges into the river between Godalming and Guildford (approx. 34.2 km below the source). Two methods are compared for reducing the counts obtained for each sample to a single index. PMID- 24221364 TI - A statistical analysis of the relationships among viable microbial populations, vegetation, and environment in a subantarctic tundra. AB - Parametric and nonparametric analyses were used to investigate the relationships between the populations of viable microbes and 4 edaphic variables - soil moisture, rainfall, temperature, and pH. Microbial populations were sampled over a 2-year period in contrasting grass and moss stands on the subantarctic island of South Georgia. Moisture was found to be the most significant edaphic variable, but there were highly significant correlations between bacterial and fungal populations at both sites. Individual plant species showed clear correlations with both bacterial and fungal populations. PMID- 24221365 TI - Biological activity in soil from forest stands in Central Sweden, as related to site properties. AB - The relationship between biological activities in samples from the forest floor and, respectively, stand (site quality class, tree age, and latitude) and soil (pH, carbon, carbon/nitrogen, and available phosphorus) properties was examined in a multi-site study performed in Central Sweden. The biological activities measured were respiration and phosphatase and dehydrogenase activity. The incubations were made in the laboratory on sieved and homogenized samples. When the biological activities were expressed on a dry matter weight basis, the concentration of organic C was the strongest predictor of respiration and phosphatase activity. In contrast, the strongest predictor of dehydrogenase activity was the pH value. Respiration and dehydrogenase activity were not significantly correlated. When excluding the influence of C concentration by expressing the activities on a C weight basis, respiration and phosphatase activity were not significantly correlated with any of the independent variables studied. Curvilinear models (polynomial equations of second and third order) gave significantly better descriptions of the relationship between respiration and, respectively, pH and C/N ratio, than linear models. Optimum conditions for respiration were indicated at intermediate pH (4-5 in 0.01 M CaCl2) and C/N ratio (20-30). The dehydrogenase activity on a C weight basis was correlated with the pH value even more strongly than it was on a dry matter basis. The phosphatase activity was not significantly correlated with the content of available P either on a dry matter basis or on a C weight basis. PMID- 24221366 TI - Microbial symbiotes of the ambrosia beetleXyloterinus politus. AB - Progression in the understanding of the microecology of ambrosia beetles and their associated microorganisms is briefly reviewed. Between the 1840s and the early 1960s the concept of one ambrosial fungus per ambrosia beetle was emphasized. Some subsequent research has supported the view that each ambrosia beetle plus several associated microorganisms constitute a highly co-evolved symbiotic community. It was hypothesized in this study that such a community of symbiotic microbial species, not just one ambrosial fungus, is actively cultivated and perpetuated by the ambrosia beetleXyloterinus politus. Experimental results indicated that bacteria, yeasts, a yeastlike fungus, and ambrosial fungi compose such a symbiotic microbial complex in association withX. politus. The microecology of the ectosymbiotic microorganisms in relation to this insect is discussed. PMID- 24221367 TI - A preliminary survey of the relative abundance of fecal coliform bacteria in water and sediment and in the fresh water bivalve,Lamellidens marginalis, of the Buriganga river, Bangladesh. AB - Studies on the concentration of fecal coliforms in freshwater bivalves were carried out using a spread plate method and membrane fecal coliform medium. Water, sediment, and bivalves collected from the Buriganga River at Dhaka, Bangladesh, were examined. As demonstrated in many previous studies, fecal coliform counts were consistently higher for the bivalve tissue than those for water and sediment samples; in the bivalveLamellidens marginalis, they were ~10.0 to 87.0-fold higher than those in water, and 2.0- to 11.0-fold higher than those in sediment. PMID- 24221368 TI - RFLP variability in peanut (Arachis hypogaea L.) cultivars and wild species. AB - RFLP variability was studied in eight U.S. peanut cultivars, representing the four market types, and in 14 wild Arachis species accessions, using random genomic clones from a PstI library. Very low levels of RFLP variability were found among the allotetraploids, which included the U.S. cultivars and Arachis monticola, a wild species. The diploid wild species were very diverse, however. RFLP patterns of the allotetraploids were more complex than the diploids, and the two constituent genomes could usually be distinguished. On the basis of RFLP band sharing, A. ipaensis, A. duranensis, and A. spegazzinii appeared most closely related to the diploid progenitor species of the allotetraploids. A dendrogram of relationships among the diploid wild species was constructed based on band sharing. PMID- 24221369 TI - Relationship between heterosis and heterozygosity at marker loci: a theoretical computation. AB - In this paper we have studied the linear correlation between a genetic distance index between two parent lines (based on marker loci information) and the heterosis observed in the F1 hybrid from the two lines, for a quantitative character (determined by several loci, or QTL). Theoretical computations of the correlation coefficient (rho) between the distance index and the heterosis were made, assuming the biallelic model (defined by Fisher). When the alleles at both marker loci and QTL are equally distributed among the whole population of considered lines, the coefficient rho is a function of the squares of linkage disequilibria between alleles at marker loci and alleles at QTL. The QTL that are not marked by marker loci and marker loci that do not mark any QTL play symmetrical roles and can decrease rho greatly. We conclude that the prediction of F1 hybrid heterosis based on marker loci would be more efficient if these markers were selected for their relationship to the alleles implicated in the heterotic traits considered. PMID- 24221370 TI - Seed set after pollination with in-vitro-matured, isolated pollen of Triticum aestivum. AB - Immature pollen of two varieties of Triticum aestivum, at the stage right after the first pollen mitosis, was isolated from individual anthers and cultured in microcultures of microliter droplets. In a specifically designed medium, some of the pollen grains developed to maturity. These were applied to excised stigmas on agar, where they produced pollen tubes. Application to flowers in vivo led to seed set. Pollen was matured in vitro from a variety that produced a different protein banding pattern on SDS-PAGE as compared to the variety that was pollinated. The protein banding in the produced seeds showed the hybrid pattern, demonstrating that the seeds were not produced by self-pollination in this in breeding species but by pollination with the in-vitro-matured pollen. PMID- 24221371 TI - pEmu: an improved promoter for gene expression in cereal cells. AB - A recombinant promoter, pEmu, has been constructed to give a high level of gene expression in monocots. It is based on a truncated maize Adh1 promoter, with multiple copies of the Anaerobic Responsive Element from the maize Adh1 gene and ocs-elements from the octopine synthase gene of Agrobacterium tumefaciens. The pEmu promoter was one of 12 different promoter constructs that were linked to the beta-glucuronidase (GUS) marker gene. Promoter activity was measured 48 h after introduction of the constructs into protoplasts of five different monocot species [wheat, maize, rice, einkorn (Triticum monococcum), and Lolium multiflorum] and one dicot (Nicotiana plumbaginifolia). In suspension cell protoplasts, the most highly expressing construct (pEmuGN) gave 10- to 50-fold higher expression than the CaMV 35S promoter in all the monocot species. The pEmu promoter should be valuable where a high level of gene expression is required in monocots. The pEmu promoter showed instability in several widely used Escherichia coli strains but was stable in a recA, recD strain AC001, which is described. Another construct, p4OCSDelta35SIGN, gave a tenfold increase in expression over the CaMV 35S promoter in dicot (Nicotiana plumbaginifolia) protoplasts. PMID- 24221372 TI - Somatic chromosome map of rice by imaging methods. AB - Rice somatic chromosomes were completely identified and quantitatively mapped based on an image parameter, condensation pattern (CP), or a chromosomal density profile determined by imaging methods. The CP corresponds to the compactness of the chromatin fibers along the chromatid, which is characteristic in small plant chromosomes such as rice chromosomes at the mitotic pro-metaphase stage. The standard CP for every chromosome was obtained by averaging 60 CPs from 30 chromosome spreads. Each standard CP exhibited a characteristic pattern of the chromosome, which enabled it to be distinguished from the other chromosomes. An ideogram based on the numerical data and the standard CP was established. The chromosomal address was also determined based on the degree of condensation, and the fractional length of each chromosomal address was quantitatively presented. PMID- 24221373 TI - Identification and characterization of somatic rice chromosomes by imaging methods. AB - Somatic rice chromosomes from 30 spreads were analyzed by imaging methods. Morphological characters of each of the 12 rice chromosomes were obtained both by the imaging methods and by visual inspection. The numerical data of relative length, arm ratio, and condensation pattern (CP) were statistically analyzed. The descriptive morphological information obtained was also summarized into numbers of "key characters" or essential short sentences to characterize the traits. The fitness probability or the appearing frequencies of the key character for each of the 30 chromosomes was calculated. Altogether, 118 key characters were extracted to distinguish each rice chromosome. Furthermore, several "discriminants" or critical key characters were determined among the key characters, and a discrimination chart or flowchart to identify all the rice chromosomes was constructed using the discriminants. PMID- 24221374 TI - Marker chromosomes commonly observed in the genus Glycine. AB - Soybean [Glycine max (L.) Merr.] chromosomes were analyzed using the chromosome image analyzing system, CHIAS, and seven groups, including subgroups, were identified based on morphological characteristics. Two pairs of chromosomes were conspicuous in their morphological traits. One pair of chromosomes, which had the largest arm ratio among all the chromosomes, was commonly observed in the species in all three subgenera of the genus Glycine. These chromosomes also displayed a unique pattern after N-banding and were detected as marker chromosomes. G. soja, which is considered to be the ancestor of G. max, has two types of marker chromosomes. The lines that carry the same type as G. max may be the ancestors of G. max among the lines of G. soja. The morphological differences of the marker chromosomes within the species in the subgenus Soja are discussed in relation to the domestication process of soybean. PMID- 24221375 TI - Isozyme gene markers in the dioecious species Asparagus officinalis L. AB - Extracts from phylloclads of Asparagus officinails were electrophoretically analyzed for isozyme polymorphism. Fourteen enzyme systems were examined using four buffer systems: seven enzymes (acid phosphatase, catalase, glutamate oxaloacetate transaminase, isocitrate dehydrogenase, malate dehydrogenase, peroxidase, and 6-phosphogluconate dehydrogenase) exhibited clear and consistent banding patterns. Isozyme polymorphism was studied in seven pairs of male and female doubled haploids and in their male F1s. Segregation of polymorphic loci was examined in the backcross progenies and was found to be consistent with a simple Mendelian inheritance in all cases, except for three anodical peroxidases, where two factors have been hypothesized. No linkage could be found between isozyme markers that were segregating in the same cross, but association was demonstrated between one malate dehydrogenase locus and the sex determining genes. The availability of isozyme markers may be useful in breeding and, in particular, the localization of one malate dehydrogenase locus on the sex chromosomes may be helpful in mapping the sex genes. PMID- 24221376 TI - Chromosomal inversions and genetic control revisited: the use of inversions in sexing systems for higher Diptera. AB - Genetic sexing systems based on sex-linked translocations and deleterious mutations are subject to breakdown from genetic recombination in males. Including inversions in these strains may provide a solution to this problem, by ensuring selective elimination of recombinant products. Inversions could be used either in coupling to or in repulsion to the translocation. The latter system, requiring homozygous-viable inversions, would be more difficult to construct, but would offer several advantages not available with coupled translocation/inversion systems. A system proposed for the blowfly Lucilia cuprina is outlined, which combines homozygous-viable pericentric inversions in repulsion to existing sex linked translocations. This system should both stabilize the genetic sexing system and increase the suppressive potential of such strains. PMID- 24221377 TI - Selection of sires to reduce sampling variance in the estimates of heritability by half-sib correlation. AB - Standard methods to estimate heritability by half-sib correlation are biased if selection has operated in the parental generation. In this paper a simple method to correct for selection of animals used as sires is described. By selection of both the top and the bottom ranking sires, the sampling variances of the corrected estimates of heritability are substantially reduced. Algebraic expressions to predict the sampling variance of the estimates of heritability using selected sires are derived. Theoretical predictions were checked by Monte Carlo simulation. The results may have application in the design of experiments to estimate heritabilities. PMID- 24221378 TI - Identification of 'Amigo' and 'Kavkaz' translocations in Ohio soft red winter wheats (Triticum aestivum L.). AB - One cultivar ('GR876') and two advanced Ohio soft red winter wheat lines ('OH413' and 'OH414'), with 'Kavkaz' in their pedigrees, were examined for the presence of the 'Kavkaz,' 1RS/1BL rye/wheat chromosome translocation. Another advanced line ('OH416'), with 'Amigo' in its pedigree, was examined for the presence of the 'Amigo,' 1RS/1AL translocation. Only two satellited chromosomes were observed in most mitotic root-tip cells from 'GR876,' 'OH413,' and 'OH414,' compared to four in most cells from 'OH416.' Heteromorphic bivalents were observed in most PMCs from hybrids produced by crossing 'GR876,' 'OH413,' and 'OH414' as females to 'Chinese Spring.' No heteromorphic bivalents were observed in PMCs from 'OH416' x 'Chinese Spring' hybrids. When 'GR876' and the Ohio lines were hybridized with 'Chinese Spring' dimonotelosomic-1B, telosomic trivalents, consisting of the short- and longarm telosomes paired with chromosome 1B, were only observed in PMCs from 43-chromosome hybrids involving 'OH416.' The long-arm telosome paired with the translocation chromosome, while the short-arm telosome remained unpaired in all other 43-chromosome hybrids. Separation of gliadin proteins from 'GR876' and the Ohio lines by PAGE revealed that secalin bands for 'GR876,' 'OH413,' and 'OH414,' migrated similarly to the secalins for 'Kavkaz.' Bands for 'OH416,' identified as possible secalins, migrated similarly to those for 'Amigo.' Cultivar 'GR876' and advanced Ohio soft red winter wheat lines 'OH413' and 'OH414' carry the 'Kavkaz' translocation, while 'OH416' carries the 'Amigo' translocation. PMID- 24221379 TI - The CAT-2 null phenotype in maize is likely due to a DNA insertion into the Cat2 gene. AB - The molecular basis for a shorter Cat2 transcript in maize lines null for the CAT 2 catalase iso/yme was investigated using cDNA libraries and genomic DNA blots. Sequence comparison of partial Cat2 cDNAs obtained from two CAT-2 null lines and a wild-type CAT-2 encoding cDNA showed that the Cat2 null transcripts diverged from the wild-type transcript but remained homologous to each other. Genomic DNA blots indicated that the missing portion of the transcript is present in the genomes of lines null for the CAT-2 isozyme. Differences in the hybridization patterns of normal and null lines were revealed when genomic DNA blots were probed with the full-length Cat2 cDNA, a Cat2 gene-specific probe, and a "null sequence" probe. Together, the DNA blotting results suggest that a rearrangement of the Cat2 gene has occurred in the CAT-2 null lines. The available data suggest that the CAT-2 null mutation in maize is due to a DNA insertion into the Cat2 gene. PMID- 24221380 TI - Quantitatively determined self-incompatibility : 3. Genetical variability in Borago officinalis. AB - It is shown by simulation that a hypothetical multilocus, quantitatively determined self-incompatibility system, whether gametophytic or sporophytic, should maintain variability in small populations at a higher level than would panmixia. Studies of more than 20 isozyme loci show that borage has almost no variability. PMID- 24221381 TI - Use of 2n pollen-producing triploid hybrids to introduce tetraploid Mexican wild species germ plasm to cultivated tetraploid potato gene pool. AB - Tetraploid (2n=4x=48) 2EBN Mexican wild species in the series Longipedicellata, which consists of Solanum fendleri, S. hjertingii, S. papita, S. polytrichon, and S. stoloniferum, were crossed with two 2EBN cultivated diploid (2n=2x=24) clones. The resulting triploid hybrids (2n=3x=36) produced 2n pollen (triplandroids) by the mechanism of parallel orientation of anaphase II spindles. The percentage of stainable pollen in 520 triploids ranged between 0 and 23.5%, with a mean of 2.7%. Triploids producing between 13.0 and 23.5% stainable pollen were crossed as staminate parents to the tetraploid cultivars, resulting in abundant pentaploid (2n=5x=60) and near-pentaploid hybrid progeny. Crosses of triploids with lower percentage of stainable pollen as pollen parent to the tetraploid cultivars did not yield fruit, unless rescue pollen from a tetraploid cultivar was added 2 days later. Pentaploid hybrids were selected among selfed tetraploid progenies using morphological and isoxyme markers transmitted from their cultivated diploid parents. These pentaploid hybrids were vigorous and had uniformly sterile pollen. They were female fertile and were crossed with tetraploid cultivars, yielding an average of 19 seeds per fruit. Triplandroids provide the opportunity of transferring 2EBN tetraploid Mexican wild species in the series Longipedicellata germ plasm into the 4EBN cultivated potatoes. PMID- 24221382 TI - Molecular characterization of a low-molecular-weight glutenin cDNA clone from Triticum durum. AB - A full-length, low-molecular-weight (LMW) glutenin cDNA clone, pTdUCD1, has been isolated from a Triticum durum cv 'Mexicali' wheat cDNA library. The complete sequence was determined and compared to the LMW glutenin genes that have been isolated from hexaploid wheat, Triticum aestivum. This cDNA codes for a protein of 295 amino acids (33,414 daltons) including a 20-amino acid signal peptide as deduced from the DNA sequence. Northern analysis showed that this cDNA hybridizes to a family of related sequences ranging in length from 1,200 to 1,000 nucleotides. This gene is similar but not identical to previously published LMW glutenin gene sequences. The most striking characteristic of all cloned LMW glutenin genes is the conservation of eight cysteine residues, which could be involved in potential secondary or tertiary structure, disulfide bond interactions. This paper presents a structural map defining distinct regions of the LMW glutenin gene family. PMID- 24221383 TI - RFLP markers linked to the root knot nematode resistance gene Mi in tomato. AB - The Mi gene originating from the wild tomato species Lycopersicon peruvianum confers resistance to all major root knot nematodes (Meloidogyne spp.). This single dominant gene is located on chromosome 6 and is very closely linked to the acid phosphatase-1 (Aps-1) locus. Resistance to nematodes has been introgressed into various cultivars of the cultivated tomato (L. esculentum), in many cultivars along with the linked L. peruvianum Aps-1 (1) allele. By using a pair of nearly isogenic lines differing in a small chromosomal region containing the Mi and Aps-1 loci, we have identified two RFLP markers, GP79 and H6A2c2, which are located in the introgressed L. peruvianum region. Analysis of a test panel of 51 L. esculentum genotypes of various origins indicated that GP79 is very tightly linked to the Mi gene and allows both homozygous and heterozygous nematode resistant genotypes to be distinguished from susceptible genotypes, irrespective of their Aps-1 alleles. Marker H6A2c2 is linked to the Aps-1 locus and is capable of discriminating between the L. peruvianum Aps-1 (1) allele and the L. esculentum Aps-1 (3) and Aps-1 (+) alleles. In combination, these RFLP markers may provide a powerful tool in breeding tomatoes for nematode resistance. PMID- 24221384 TI - Gene-enzyme relations in the pathway of flavonoid biosynthesis in barley. AB - Mutations in genes associated with the pathway of flavonoid biosynthesis can be easily induced in barley, and more than 600 mutants have been isolated in which the biosynthesis of proanthocyanidins is genetically blocked. Diallelic crosses have localized a majority of the proanthocyanidin-free mutants to nine different ant genes. In order to characterize the ant gene assays for flavanone 3 hydroxylase, flavonoid 3'-hydroxylase and dihydroflavonol reductase activities in protein extracts from developing grains of proanthocyanidin-free mutants in six ant genes and wild-type barley were performed. The presence of chalcone synthase enzyme protein in wild-type barley and the mutant ant 13-152 was investigated by SDS-PAGE, protein blotting, and reaction with an antiserum against parsley chalcone synthase. The results of these experiments combined with earlier studies of flavonoid content in barley grains of different genotypes characterize the functions of six ant genes as follows. The gene ant 13 is a regulatory gene affecting the transcription of structural genes in the flavonoid pathway. The genes ant 17 and ant 22 are probably coding for different components necessary for hydroxylation of flavanones in 3-position. The gene ant 18 is the structural gene coding for dihydroflavonol reductase, and ant 19 is most likely the structural gene coding for leucoanthocyanidin reductase. Ant 21 is probably a regulatory gene affecting the biosynthesis of proanthocyanidins and anthocyanins. PMID- 24221385 TI - Direct effect of colchicine on the microspore embryogenesis to produce dihaploid plants in wheat (Triticum aestivum L.). AB - In the present experiment, different chromosome reduplication techniques were applied to microspore-originated Triticum aestivum L. (cv 'Ciano') haploids. In addition to the conventional treatment (whole plant exposure to colchicine solution), spontaneously redoubled haploids were also examined. As an experimental treatment, different concentrations (0.01, 0.02, 0.04%) of colchicine were added directly to the induction media. Colchicine did not affect the anther response or the plant regeneration capacity. The success and stability of genome redoubling was estimated on the basis of the fertility of the regenerated (R0) plants and their progeny (R1). Chromosome doubling produced by colchicine before the first microspore mitosis was significantly more efficient than the conventionally used techniques. PMID- 24221386 TI - An integrated approach to oilseed rape cultivar selection using phenotypic stability. AB - Various methods of evaluating phenotypic stability have been proposed; however, no single method can adequately describe cultivar performance. The objectives of this study were to integrate a number of methods of evaluating stability and to use this approach for cultivar selection. These objectives were considered in the context of the broad-based oilseed rape cultivar (Brassica napus spp. oleifera) evaluation system currently used in western Canada. Regression analysis was used to assess cultivar response to environments. Cluster analysis was used to assemble cultivars into groups with similar regression coefficients (b i ) and mean yield. Three parametric stability parameters, years within locations mean square (MS; Y/L), Shukla's stability variance (sigma i (2) ), and Francis and Kannenberg's coefficient of variability (CV i ), were compared to determine which method would be most suitable for selection of oilseed rape cultivars from within clustered groups. Yield data from three cultivars and six breeding lines that had been tested for 2 years at 26 locations in the Western Canola Cooperative Test 'A' were used for all calculations. The cluster analysis was successful in identifying commercially acceptable breeding lines. The parameter MS i Y/L was considered to be more appropriate than either CV i or sigma i (2) , because it measured only the unpredictable portion of the genotype x environment interaction and was independent of the other cultivars in the test. The use of cluster analysis to group entries with similar b i values and mean yields, followed by selection for stability within groups, was advocated. PMID- 24221387 TI - Replicated selection for insulin-like growth factor-1 and body weight in mice. AB - Five generations of divergent selection for plasma concentration of insulin-like growth factor-1 (IGF-1) and for 12-week body weight were carried out in mice, including randomly selected control lines for each trait. All lines were replicated once (12 lines in total). Each replicate line consisted of eight male and eight female parents per generation. Litter size was standardized to eight pups at birth. Mass selection was applied in the selected lines and within-family random selection in the control lines. Blood was taken from the orbital sinus of individual mice at 12 weeks of age for IGF-1 assay. Realized heritabilities were 0.10+/-0.01 for IGF-1 and 0.41 +/- 0.02 for 12-week weight. The realized genetic correlation between IGF-1 and 12-week weight was 0.58 +/- 0.01, with a phenotypic correlation of 0.38. Although the genetic correlation between IGF-1 and body weight in mice is moderately positive, 12-week weight responded 3.5 times as fast to weight selection as to selection for IGF-1. PMID- 24221388 TI - Phylogenetic relationships of annual and perennial wild rice: probing by direct DNA sequencing. AB - The phylogenetic relationships between Asian wild rice strains were analyzed by direct sequencing of PCR-amplified DNA fragments. The sequence of three introns located in the phytochrome gene was determined for eight strains of the Asian wild rice, Oryza rufipogon, and one strain of the related African species, Oryza longistaminata. The number of nucleotide substitutions per site between various strains within a single species, O. rufipogon, ranged between 0.0017 and 0.0050, while those between two related species, O. rufipogon and O. longistaminate, were 0.043-0.049 (23-26 within 532 bp). Taken together with the sequence differences of the 10-kDa prolamin gene, a model is proposed for the phylogenetic relationships and evolutionary history of annuals and perennials within O. rufipogon. PMID- 24221389 TI - Analyses of Phaseolus vulgaris L. and P. coccineus Lam. hybrids by RFLP: preferential transmission of P. vulgaris alleles. AB - Restriction fragment length polymorphism (RFLP) was determined among P. vulgaris genotypes and Phaseolus species using 19 probes. The incidence of polymorphism was high (70-86%) between species, but relatively low (22-26%) between genotypes of P. vulgaris. Suitable probes were identified for the analysis of P. vulgaris and P. coccineus hybrids. The segregation pattern in F2 populations was Mendelian for two probes (LHB and VEE20) and non-Mendelian for GS-g, CHS, and CHI. Statistical analyses indicated gametic selection with preferential transmission of the P. vulgaris alleles, which may account for the selective recovery of P. vulgaris progeny types observed earlier. The available hybrids of P. vulgaris and P. coccineus and the high degree of interspecific RFLP will facilitate the construction of a linkage map for Phaseolus. PMID- 24221390 TI - Adventitial nab-rapamycin injection reduces porcine femoral artery luminal stenosis induced by balloon angioplasty via inhibition of medial proliferation and adventitial inflammation. AB - BACKGROUND: Endovascular interventions on peripheral arteries are limited by high rates of restenosis. Our hypothesis was that adventitial injection of rapamycin nanoparticles would be safe and reduce luminal stenosis in a porcine femoral artery balloon angioplasty model. METHODS AND RESULTS: Eighteen juvenile male crossbred swine were included. Single-injury (40%-60% femoral artery balloon overstretch injury; n=2) and double-injury models (endothelial denudation injury 2 weeks before a 20%-30% overstretch injury; n=2) were compared. The double injury model produced significantly more luminal stenosis at 28 days, P=0.002, and no difference in medial fibrosis or inflammation. Four pigs were randomized to the double-injury model and adventitial injection of saline (n=2) or 500 MUg of nanoparticle albumin-bound rapamycin (nab-rapamycin; n=2) with an endovascular microinfusion catheter. There was 100% procedural success and no difference in endothelial regeneration. At 28 days, nab-rapamycin led to significant reductions in luminal stenosis, 17% (interquartile range, 12%-35%) versus 10% (interquartile range, 8.3%-14%), P=0.001, medial cell proliferation, P<0.001, and fibrosis, P<0.001. There were significantly fewer adventitial leukocytes at 3 days, P<0.001, but no difference at 28 days. Pharmacokinetic analysis (single-injury model) found rapamycin concentrations 1500* higher in perivascular tissues than in blood at 1 hour. Perivascular rapamycin persisted >=8 days and was not detectable at 28 days. CONCLUSIONS: Adventitial nab-rapamycin injection was safe and significantly reduced luminal stenosis in a porcine femoral artery balloon angioplasty model. Observed reductions in early adventitial leukocyte infiltration and late medial cell proliferation and fibrosis suggest an immunosuppressive and antiproliferative mechanism. An intraluminal microinfusion catheter for adventitial injection represents an alternative to stent- or balloon based local drug delivery. PMID- 24221391 TI - Outcomes of transcatheter and surgical aortic valve replacement in high-risk patients with aortic stenosis and left ventricular dysfunction: results from the Placement of Aortic Transcatheter Valves (PARTNER) trial (cohort A). AB - BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial demonstrated similar survival after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively) in high-risk patients with symptomatic, severe aortic stenosis. The aim of this study was to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after TAVR and SAVR and the impact of aortic valve replacement technique on LV function. METHODS AND RESULTS: The PARTNER trial randomized high-risk patients with severe aortic stenosis to TAVR or SAVR. Patients were stratified by the presence of LV ejection fraction (LVEF) <50%. All-cause mortality was similar for TAVR and SAVR at 30-days and 1 year regardless of baseline LV function and valve replacement technique. In patients with LV dysfunction, mean LVEF increased from 35.7+/-8.5% to 48.6+/ 11.3% (P<0.0001) 1 year after TAVR and from 38.0+/-8.0% to 50.1+/-10.8% after SAVR (P<0.0001). Higher baseline LVEF (odds ratio, 0.90 [95% confidence interval, 0.86, 0.95]; P<0.0001) and previous permanent pacemaker (odds ratio, 0.34 [95% confidence interval, 0.15, 0.81]) were independently associated with reduced likelihood of >=10% absolute LVEF improvement by 30 days; higher mean aortic valve gradient was associated with increased odds of LVEF improvement (odds ratio, 1.04 per 1 mm Hg [95% confidence interval, 1.01, 1.08]). Failure to improve LVEF by 30 days was associated with adverse 1-year outcomes after TAVR but not SAVR. CONCLUSIONS: In high-risk patients with severe aortic stenosis and LV dysfunction, mortality rates and LV functional recovery were comparable between valve replacement techniques. TAVR is a feasible alternative for patients with symptomatic severe aortic stenosis and LV dysfunction who are at high risk for SAVR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. PMID- 24221392 TI - Simple agrometeorological models for estimating Guineagrass yield in Southeast Brazil. AB - The objective of this work was to develop and evaluate agrometeorological models to simulate the production of Guineagrass. For this purpose, we used forage yield from 54 growing periods between December 2004-January 2007 and April 2010-March 2012 in irrigated and non-irrigated pastures in Sao Carlos, Sao Paulo state, Brazil (latitude 21 degrees 57'42" S, longitude 47 degrees 50'28" W and altitude 860 m). Initially we performed linear regressions between the agrometeorological variables and the average dry matter accumulation rate for irrigated conditions. Then we determined the effect of soil water availability on the relative forage yield considering irrigated and non-irrigated pastures, by means of segmented linear regression among water balance and relative production variables (dry matter accumulation rates with and without irrigation). The models generated were evaluated with independent data related to 21 growing periods without irrigation in the same location, from eight growing periods in 2000 and 13 growing periods between December 2004-January 2007 and April 2010-March 2012. The results obtained show the satisfactory predictive capacity of the agrometeorological models under irrigated conditions based on univariate regression (mean temperature, minimum temperature and potential evapotranspiration or degreedays) or multivariate regression. The response of irrigation on production was well correlated with the climatological water balance variables (ratio between actual and potential evapotranspiration or between actual and maximum soil water storage). The models that performed best for estimating Guineagrass yield without irrigation were based on minimum temperature corrected by relative soil water storage, determined by the ratio between the actual soil water storage and the soil water holding capacity.irrigation in the same location, in 2000, 2010 and 2011. The results obtained show the satisfactory predictive capacity of the agrometeorological models under irrigated conditions based on univariate regression (mean temperature, potential evapotranspiration or degree-days) or multivariate regression. The response of irrigation on production was well correlated with the climatological water balance variables (ratio between actual and potential evapotranspiration or between actual and maximum soil water storage). The models that performed best for estimating Guineagrass yield without irrigation were based on degree-days corrected by the water deficit factor. PMID- 24221393 TI - Optimization of maize microspore isolation and culture conditions for reliable plant regeneration. AB - The effects of different factors were investigated in the process of isolated microspore culture of Zea mays L., Using donor plants grown in standard conditions and an efficient isolation technology, homogeneous populations of viable microspores at specific developmental stages were obtained and tested in culture. The cytological evolution of the microspores during the first week of culture was monitored using a DNA-specific fluorochrome. It was found that developmental stages of microspores, number of days of pretreatment at 7 degrees C of the tassel, and culture density greatly influenced the number of microspore derived embryos. Optimal conditions required for embryo and plant production are described. PMID- 24221394 TI - Phenylpropanoid defence responses in transgenic Lotus corniculatus 1. Glutathione elicitation of isoflavan phytoalexins in transformed root cultures. AB - When Agrobacterium rhizogenes transformed root cultures of Lotus corniculatus were treated with glutathione, isoflavan phytoalexins accumulated in both tissue and culture medium. This accumulation of phytoalexins was preceded by a transient increase in the activity of phenylalanine ammonia lyase (PAL). Elicitation of PAL occurred throughout the growth curve of Lotus 'hairy roots' and in different sectors of transformed root material. PMID- 24221395 TI - Osmotic potential of media affecting green plant percentage in wheat anther culture. AB - The percentage of green plants in anther culture is known to be controlled by the genetics of anther donor materials. The objective of this study was to determine whether components in the culture media also would have a significant influence on the percentage of green plants from wheat anther culture. Anthers of a spring wheat cultivar, "Pavon 76", were cultured on potato 4 (P4) induction media with various modifications. Addition of 200 g/l ficoll to the liquid P4 medium significantly increased the percentage of green plants even though the final yield of green plants per 100 anthers was lower than the liquid medium. A higher concentration of maltose (135 g/l) produced significantly higher percentage of green plants than the medium containing 90 g/l maltose or sucrose. These results demonstrate culture medium effects on albinism, indicating that the percentage of green plants in wheat anther culture can be increased by optimizing medium osmotic potential. PMID- 24221396 TI - In vitro propagation of Coleus forskohlii Briq., a threatened medicinal plant. AB - In vitro clonai multip1ication of Coleus forskahlii Briq a threatened plant, has been achieved on MS medium supplemented with Kn (2.0 mg/l) and IAA (1.0 mg/l) using nodal segments as explants, Shoots multiplied at a rate of 12 - fold every six weeks. Rooting was achieved upon transfer of shoots onto MS medium containing IAA (1.0 mg/l). The micropropagated plants were successfully established under field conditions. Forskolin content in tubers of plants obtained by micropropagation was found to be 0.1%, the same as that found in wild plants. This micropropagation procedure should be useful for conservation as well as production of this important plant. PMID- 24221397 TI - Somatic embryogenesis in asparagus: the role of explants and growth regulators. AB - The explant used to initiate embryogenic callus and the growth regulators used in subsequent induction (IM) and embryo development media (EDM) both influenced rate of somatic embryo development and conversion to plantlets in asparagus. Embryogenic callus derived from spear-cross sections (SS), in vitro crowns (IVC) and lateral buds (LB) was cultured on IM of MS salts and vitamins with 2, 4-D or NAA at 0, 0.01, 0.1, 1.0 or 10 mg/l and kinetin at 0, 0.1, 1.0 or 10 mg/l. The auxin 2,4-D at 1-10 mg/l, in combination with kinetin at 0-1 mg/l, in IM induced the highest frequency of embryos after four weeks; callus derived from SS, IVC and LB had means of 394, 382, and 344 small globular embryos, and 4, 11 and 9 bipolar embryos per gram of callus, respectively. After 6 weeks on EDM, 128, 116 and 51 bipolar embryos (4-7 mm in length) occurred per gram callus and 4.5, 1.4 and 2.1 embryos converted for IVC, SS and LB, respectively. NAA at 1-10 mg/l, in combinations with kinetin 0-1 mg/l, yielded means of 64, 175 and 225 small globular embryos per gram callus on IM for SS, IVC and LB, respectively. NAA promoted a higher rate of embryo development: means of 27, 54 and 91 bipolar embryos per gram callus for SS, LB and IVC, respectively, on EDM. There were 0.5, 9.4 and 11.9 plantlets from these respective callus sources. There was no difference between kinetin levels of 0-1 mg/l on callus growth and embryogenesis, whereas, 10 mg/l in IM was inhibitory. PMID- 24221398 TI - Somatic hybridization between selected Lycopersicon and Solanum species. AB - Mesophyll protoplasts of an interspecific Lycopersicon esculentum Mill, (tomato) x Lycopersicon pennellii hybrid plant (EP) were fused with callus-derived protoplasts of Solanum lycopersicoides Dun. using a modified PEG/DMSO procedure. The EP plant was previously transformed by Agrobacterium tumefaciens which carried the NPTII and nopaline synthase genes. Protoplasts were plated at 10(5)/ml in modified KM medium and 16 days post-fusion 25 ug/ml kanamycin was added to the culture medium. During shoot regeneration, 212 morphologically similar putative somatic hybrids were delineated visually from kanamycin resistant EP's. Forty-eight shoots, randomly selected among the 212, were further verified as somatic hybrids by their leaf phosphoglucoisomerase heterodimer isozyme pattern. However, the resulting plants were virtually pollen sterile. In a second fusion, mesophyll protoplasts of Solanum melongena (eggplant) were fused with EP callus-derived protoplasts. Using the same fusion and culture procedure, only two dark green calli were visually selected among the pale green parental EP and verified as somatic cell hybrids by several isozyme patterns. These two calli have produced only leaf primordia in one and half years on regeneration medium. PMID- 24221399 TI - Cell growth and water relations of the halophyte, Atriplex nummularia L., in response to NaCl. AB - Growth reduction or cessation is an initial response of Atriplex nummularia L. cells to NaCl. However, A. nummularia L. cells that are adapted to 342 and 428 mM NaCl are capable of sustained growth in the presence of salt. Cells that are adapted to NaCl exhibit a reduced rate of division compared to unadapted cells. Unlike salt adapted cells of the glycophyte Nicotiana tabacum L., A. nummularia L. cells do not exhibit reduced rate of cell expansion after adaptation. However, the cell expansion rate of unadapted A. nummularia L. cells is considerably slower than that of unadapted glycophyte cells and this normally low rate of cell expansion may contribute to the enhanced capacity of the halophyte to tolerate salt. Turgor of NaCl adapted cells was equivalent to unadapted cells indicating that the cells of the halophyte do not respond to salt by osmotic "over adjustment" as reported for the glycophyte tobacco (Binzel et al. 1985, Plant Physiol. 79:118-125). PMID- 24221401 TI - Effect of culture conditions on Agrobacterium-mediated transformation in datura. AB - A two step selection procedure is described for high frequency transformation and regeneration of transgenic plants by coculture of leaf discs of Datura innoxia with Agrobacterium tumefaciens carrying binary vectors. Leaf discs were cocultured with disarmed A. tumefaciens vectors pGS Glucl, pGSTRN943, pGV2260 and pBI121, and subcultured on regeneration media containing kanamycin. Kanamycinresistant, putatively "transformed" callus and vegetative buds were isolated, and subcultured on media containing reduced amounts of growth regulators and kanamycin to induce shooting. Rooted shoots produced normal fertile plants. Transformation frequency was related to duration of preculture, co-culture, and the bacterial strain used. With pGS Glue 1, a 3 day co-culture resulted in 70% of leaf discs being transformed. Transformation was confirmed by histochemical test for GUS activity, by the ability of leaf discs to initiate callus and from NPTII test, and Southern blot analysis. Progeny of the transgenic plants showed Mendelian segregation for kanamycin resistance. PMID- 24221400 TI - Agrobacterium rhizogenes-mediated transformation of Echinacea purpurea. AB - Echinacea purpurea seedlings were inoculated with several Agrobacterium rhizogenes strains in order to obtain hairy roots. Infection with A. rhizogenes strains LMG63 and LMG150 resulted in callus formation. Upon infection with strains ATCC 15834 and R1601 hairy roots were obtained. Opine detection confirmed transformation of E. purpurea. Comparative HPLC fingerprint analysis of the alkamides from natural plant source, control tissues, and transformed callus and roots indicated that transformed callus and hairy roots might be a promising source for continuous and standardized production of the dodeca-2E,4E,8Z,10E/Z tetraenoic acid isobutylamide and related amides. PMID- 24221402 TI - Micropropagation of meadowfoam (Limnanthes spp.). AB - A rapid micropropagation system was developed for meadowfoam (Limnanthes spp. Brown) using four genotypes of three species. Murashige and Skoog (MS) medium supplemented with N(6) benzyladenine (BA) and indole-3-acetic acid (IAA) at 0, 0.1, 0.5, 1.0 and 2.0 mg/l was tested for multiplication, shoot elongation and rooting. Expiants were taken from pot-grown plants. The most useful level for shoot growth and multiplication of both floral induced and non-induced plants was 0.5 mg/l BA. IAA failed to affect shoot growth or multiplication. Expiants from non-induced plants multiplied at moderate to high rates on 0.5 mg/l BA, while those from induced plants multiplied slowly and tended to elongate and flower. Non-induced plants on 2 mg/l BA produced large numbers of tiny shoots; induced plants did not respond. Shoots of all genotypes rooted on MS medium without hormones and all plants grew normally after transplanting to soil. This system provides a new tool for the development of meadowfoam as a crop plant. PMID- 24221403 TI - Regeneration of transformed shoots from electroporated soybean (Glycine max (L.) Merr.) protoplasts. AB - Stable transformation of soybean (Glycine max (L.) Merr.) protoplasts isolated from immature cotyledons was achieved following electroporation with plasmid DNA carrying chimeric genes encoding beta-glucuronidase (GUS) and hygromycin phosphotransferase (HPT) under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Transformed colonies were stringently selected by growing 15-day old protoplast-derived cells in the presence of 40 MUg/ml of hygromycin-B for 6 weeks. Over 93% of the resistant cells and colonies exhibited GUS activity, indicating that the two marker genes borne on a single plasmid were co-introduced and co-expressed at a very high freguency. This transformation procedure reproducibly yields transformants at frequencies of 2.9-6.8 * 10(-4) (based on the number of protoplasts electroporated) or 23.0% (based on the number of control microcalli formed) counted after 6 weeks of selection. After repeated subculturing on regeneration medium, shoots were induced from 8.0% of the transformed calli. Southern hybridization confirmed the presence of both the GUS and hygromycin genes in the transformed calli and shoots. PMID- 24221404 TI - Somatic embryogenesis from leaf protoplasts of Rauvolfia vomitoria shoot cultures. AB - Rauvolfia vomitoria mesophyll protoplasts have been isolated from axenic shoot cultures and cultured (10(5)-10(6) protoplasts per ml) in Murashige and Tucker liquid medium containing growth regulators. Within 6-8 weeks, a mixed population of calli and proembryos were obtained and transferred on solid media. Calli produced shoots; however, rooting did not occur. Somatic embryos achieved different patterns of development. In particular, whole plantlets have been obtained either directly through germination of primary embryos or via embryogenic calli. PMID- 24221405 TI - Factors affecting transient gene expression in electroporated Glycine max protoplasts. AB - Electroporation was used to evaluate parameters affecting transient gene expression in Glycine max protoplasts. Protoplast viability and reporter enzyme activity for chloramphenicol acetyl transferase (CAT) and beta-glucuronidase (GUS) depended on the field strength employed. Maximum CAT and GUS activity was obtained when a field strength of 500 V/cm at 1000 MUF and a protoplast concentration of 1-3 * 10(6)/ml was used. Transformation efficiencies up to approximately 1.6% GUS positive protoplasts were obtained. Transient gene expression increased with increasing plasmid DNA concentration and with the time after electroporation, reaching a maximum after 48 hr. Addition of polyethylene glycol at 5.6% and heat shock (5 rain at 45 degrees C) given to the protoplasts before adding DNA further enhanced the transformation efficiency. Under the optimized experimental conditions, CAT and GUS activity increased simultaneously, thereby indicating that the increased expression is caused by DNA uptake by more cells rather than greater DNA uptake by the same cells. Our results demonstrate that both GUS and CAT can be used as efficient screenable markers for transformation studies in soybean. PMID- 24221406 TI - Resilience in international migrant women following violence associated with pregnancy. AB - Exposure to violence associated with pregnancy (VAP) is an underrecognized public health and social problem that has an enormous impact on the physical and mental health of women and their children. Our recent study of 1,127 new mothers living in two urban areas of Canada found refugees and asylum-seekers to be more likely to have experienced VAP than immigrant or Canadian-born women. Interestingly, some migrants who had experienced VAP had low rates of postpartum depression risk on the Edinburgh Postpartum Depression Scale, suggesting that resilience may play an important role in maintaining their mental health. Hence, we sought to explore processes which enhance migrants' resilience to VAP. We conducted in-depth interviews with ten women who had been identified as experiencing VAP and having low risk of postpartum depression and performed thematic analyses. International migrant women found internal psychological and coping resources, external social supports, and systemic factors including government policies to be vital to their resilience. Participants perceived differences in resilience by gender and immigration status. International migrant women used a range of processes to maintain and enhance their resilience after VAP, and these may be helpful to less resilient women who are vulnerable to postpartum depression. PMID- 24221407 TI - Risk factors for depressive symptoms in adolescent pregnancy in a late-teen subsample. AB - Depression in adolescent pregnancy is common but underrecognized and can be associated with negative medical outcomes. This brief report examines the relationship between depressive symptoms and various demographic and obstetrical risk factors, as well as the use of antidepressants in pregnant adolescents of late teenage years. Data were derived from a relatively large sample (506 women) recruited from university-based and community mental health centers in Iowa. A cross-sectional analysis did not reveal significant statistical associations between the risk factors and depressive symptoms (Beck Depression Inventory). Antidepressant use was very low (3.7 %), and adolescents with higher depression scores were more likely to take medications. In conclusion, screening for depression in pregnant adolescents should be universal, regardless of demographic and obstetrical risk factors, and promptly addressed. PMID- 24221409 TI - Differential TIMP3 expression affects tumor progression and angiogenesis in melanomas through regulation of directionally persistent endothelial cell migration. AB - The angiogenic potential of solid tumors, or the ability to initiate neovasculature development from pre-existing host vessels, is facilitated by soluble factors secreted by tumor cells and involves breaching of extracellular matrix barriers, endothelial cell (EC) proliferation, migration and reassembly. We evaluated the angiogenic potential of human melanoma cell lines differing in their degree of aggressiveness, based on their ability to regulate directionally persistent EC migration. We observed that conditioned-medium (CM) of the aggressive melanoma cell line BLM induced a high effective migratory response in ECs, while CMs of Mel57 and 1F6 had an inhibitory effect. Further, the melanoma cell lines exhibited a varied expression profile of tissue inhibitor of metalloproteinase-3 (TIMP3), detectable in the CM. TIMP3 expression inversely correlated with aggressiveness of the melanoma cell line, and ability of the respective CMs to induce directed EC migration. Interestingly, TIMP3 expression was found to be silenced in the BLM cell line, concurrent with its role as a tumor suppressor. Treatment with recombinant human TIMP3 and CM of modified, TIMP3 expressing, BLM cells mitigated directional EC migration, while CM of TIMP3 silenced 1F6 cells induced directed EC migration. The functional implication of TIMP3 expression on tumor growth and angiogenic potential in melanoma was evaluated in vivo. We observed that TIMP3 expression reduced tumor growth, angiogenesis and macrophage infiltration of BLM tumors while silencing TIMP3 increased tumor growth and angiogenesis of 1F6 tumors. Taken together, our results demonstrate that TIMP3 expression correlates with inhibition of directionally persistent EC migration and adversely affects the angiogenic potential and growth of melanomas. PMID- 24221408 TI - Exposure to childhood traumas ups the odds of giving birth to daughters. AB - This study examined the likelihood of giving birth to a daughter as a function of women's exposure to four categories of stressors: childhood trauma, adult trauma, chronic stressors, and recent (adverse) life events. Hypothesis 1 stated that exposure to recent life events (near conception) and to childhood traumas would increase women's chances of having a girl baby. Hypothesis 2 stated that the relationship between stress and gender outcome is mediated by persistent posttraumatic stress disorder (PTSD) symptoms. The final sample was comprised of 225 women. The design was prospective observational. At first contact, women were retained if they were <27 weeks pregnant and met initial inclusion criteria. In interview 2, at 27-30 weeks, women were excluded for positive diagnoses of anxiety disorders besides PTSD with or without depression (Structured Clinical Interview for DSM-IV Disorders). In interview 3 (30-34 weeks), reports on stress categories (Social Stress Indicator Questionnaire) and PTSD symptoms (Post Traumatic Checklist) were obtained. Infant gender was obtained from medical records. The relationship between stress categories and the distribution of girl/boy infants was examined with Chi Squares and logistic regression analyses. Mediation was tested with the macro PROCESS (Hayes 2012). Childhood trauma was the only stress category that increased the odds of having a girl, with an odds ratio of >3.0 for women who had been exposed to more than two such events. PTSD symptoms (partially) mediated the relationship between childhood trauma and infant gender. Findings suggest that women's exposure to childhood trauma contributes to the determination of the sex ratio at birth and that PTSD symptoms are part of the cause. PMID- 24221410 TI - The integration of whole-root and cellular hydraulic conductivities in cereal roots. AB - The hydraulic conductivities of excised whole root systems of wheat (Triticum aestivum L. cv. Atou) and of single excised roots of wheat and maize (Zea mays L. cv. Passat) were measured using an osmotically induced back-flow technique. Ninety minutes after excision the values for single excised roots ranged from 1.6.10(-8) to 5.5.10(-8) m.s(-1).MPa(-1) in wheat and from 0.9.10(-8) to 4.8.10( 8) m.s(-1).MPa(-1) in maize. The main source of variation was a decrease in the value as root length increased. The hydraulic conductivities of whole root systems, but not of single excised roots, were smaller 15 h after excision. This was not caused by occlusion of the xylem at the cut end of the coleoptile. The hydraulic conductivities of epidermal, cortical and endodermal cells were measured using a pressure probe. Epidermal and cortical cells of both wheat and maize roots gave mean values of 1.2.10(-7) m.s(-1).MPa(-1) but in endodermal cells (measured only in wheat) the mean value was 0.5.10(-7) m.s(-1).MPa(-1). The cellular hydraulic conductivities were used to calculate the root hydraulic conductivities expected if water flow across the root was via transcellular (vacuole-to-vacuole), apoplasmic or symplasmic pathways. The results indicate that, in freshly excised roots, the bulk of water flow is unlikely to be via the transcellular pathway. This is in contrast to our previous conclusion (H. Jones, A.D. Tomos, R.A. Leigh and R.G. Wyn Jones 1983, Planta 158, 230-236) which was based on results obtained with whole root systems of wheat measured 14-15 h after excision and which probably gave artefactually low values for root hydraulic conductivity. It is now concluded that, near the root tip, water flow could be through a symplasmic pathway in which the only substantial resistances to water flow are provided by the outer epidermal and the inner endodermal plasma membranes. Further from the tip, the measured hydraulic conductivities of the roots are consistent with flow either through the symplasmic or apoplasmic pathways. PMID- 24221411 TI - The action potential of Dionaea muscipula Ellis. AB - The intention of this investigation was to acquire more concise information about the nature of the action potential of Dionaea muscipula Ellis and the different types of cells generating and conducting it. It is shown by microelectrode measurements that, besides the sensory cells, all the major tissues of the trap lobes are excitable, firing action potentials with pronounced after hyperpolarizations. The action potentials are strictly dependent on Ca(2+). Their peak depolarizations are shifted 25-27 mV in a positive direction after a tenfold increase in external Ca(2+) concentration. Perfusions with 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM LaCl3 completely inhibit excitability. Magnesium ions only slightly affect the peak depolarizations but considerably prolong action potentials. Sodium azide and 2,4 dinitrophenol also abolish excitation, probably by reducing the intracellular ATP concentration. Furthermore, it is tested whether the sensory cells can be distinguished from the other cells of the trap by their electrical behaviour. The resting potentials of sensory cells (-161+/-7 mV) and mesophyll cells (-155+/-8 mV) are of the same magnitude. Changes in external ion concentrations affect resting and action potentials in both cell types in a similar way. Additional freeze-fracture studies of both cell types reveal similar numbers and distributions of intramembrane particles on the fracture faces of the plasma membrane, which is most likely the mechanosensor. These findings stress the view that the high mechanosensitivity of the sensory hair results from its anatomy and not from a specialized perception mechanism. It is proposed that trap closure is triggered by a rise in the cytoplasmic concentration of Ca(2+) or a Ca(2+) activated regulatory complex, which must exceed a threshold concentration. Since the Ca(2+) influx during a single action potential does not suffice to reach this threshold, at least two stimulations of the trap are necessary to elicit movement. PMID- 24221412 TI - Phytochrome-controlled ethylene biosynthesis of intact etiolated bean seedlings. AB - Intact etiolated bean (Phaseolus vulgaris L. cv. Limburgse vroege) seedlings were illuminated with red light (10.5 W.m(-2)) for 10 min. After different time intervals ethylene production, and contents of 1-aminocyclopropane-1-carboxylic acid (ACC) and 1-(malonylamino)cyclopropane-1-carboxylic acid were measured. The red-light-induced decrease of ethylene production in 8-d-old intact etiolated bean seedlings was fast, strong and long-lasting ad was mediated through the phytochrome system. This effect appeared to be strictly age-dependent, as it could not be detected in plants younger than 6 d or older than 11 d.The capacity for the conversion of ACC to ethylene was not affected by red light. The inhibitory effect of the light treatment on ethylene production could be related to a reduced free-ACC content. This reduction was a consequence of a temporary non-reversible increase of ACC malonylation and a long-lasting, for a certain time reversible, inhibition of ACC synthesis. The effect of a brief irradiation with red light on the decrease of ethylene production and free-ACC content was completed after about 2 h. Reversibility by far-red, however, persisted for at least 3 h, and was lost between 3 and 6 h. PMID- 24221413 TI - Plant regeneration from protoplasts of Sphacelaria (Phaeophyceae). AB - Protoplast were isolated from a filamentous brown alga, Sphacelaria sp. (Sphacelariales, Phaeophyta), using alginate-lyases extracted from marine molluscs, and commercial pectinase and cellulase. Yields were about 4000 protoplasts per gram of fresh tissue. Different types of protoplasts, originating from apical, subapical, nodal and internodal cells, could be readily identified based on their size and pigmentation. Apical cells produced a higher percentage of protoplasts (approx. 2%), compared with other cell types. All apical-cell protoplasts regenerated into new thalli and most other types of protoplasts divided at least once in culture, but did not develop further. PMID- 24221414 TI - Differences between wheat and rice in the enzymic properties of ribulose-1,5 bisphosphate carboxylase/oxygenase and the relationship to photosynthetic gas exchange. AB - The kinetic parameters of ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (EC 4.1.1.39) in wheat (Triticum aestivum L.) and rice (Oryza sativa L.) were determined by rapidly assaying the leaf extracts. The respective K m and V max values for carboxylase and oxygenase activities were significantly higher for wheat than for rice. In particular, the differences in the V max values between the two species were greater. When the net activity of CO2 exchange was calculated at the physiological CO2-O2 concentration from these kinetic parameters, it was 22% greater in wheat than in rice. This difference in the in vitro RuBP-carboxylase/oxygenase activity between the two species reflected a difference in the CO2-assimilation rate per unit of RuBP-carboxylase protein. However, there was no apparent difference in the CO2-assimilation rate for a given leaf-nitrogen content between the two species. When the RuBP carboxylase/oxygenase activity was estimated at the intercellular CO2 pressure from the enzyme content and kinetic parameters, these estimated enzyme activities in wheat and rice were similar to each other for the same rate of CO2 assimilation. These results indicate that the difference in the kinetic parameters of RuBP carboxylase between the two species was offset by the differences in RuBP-carboxylase content and conductance for a given leaf-nitrogen content. PMID- 24221415 TI - Reevaluation of the changes in polygalacturonases in tomatoes during ripening. AB - A procedure was developed for the differential extraction of polygalacturonases (PG) I and II from tomatoes (Lycopersicon esculentum Mill.). Extraction of pericarp tissue from ripe fruit at conventional conditions of 1.0 M NaCl and pH 6.0 yielded nearly equal amounts of the two enzymes. However, most of the PG activity could be extracted also with water at pH 1.6, and the water extract contained only PG II. Subsequent extraction of the pellet with 1.0 M NaCl at pH 6.0 and 10.0 yielded some PG I and high levels of PG converter, the protein in tomatoes that reacts with PG II to form PG I. Application of this procedure to tomatoes at different stages of ripening showed that PG II appeared as ripening began and then increased during ripening. Much lower levels of PG I than of PG II were extracted at all stages of ripeness. The PG converter was present in unripe fruit and increased during ripening. The results demonstrate that PG I is formed when PG II and PG converter are solubilized simultaneously and that PG II is the only endogenous PG in tomatoes. PMID- 24221416 TI - Redox activity and peroxidase activity associated with the plasma membrane of guard-cell protoplasts. AB - Redox systems have been reported in the plasma membrane of numerous cell types and in cells from various species of higher plant. A search for a redox system in the plasma membrane of guard cells was therefore made in efforts to explain how blue light stimulates stomatal opening, a process which is coupled to guard cell H(+) efflux and K(+) uptake. The rates of O2 uptake by intact guard-cell protoplasts (GCP) of Commelina communis L., in the dark, were monitored in the presence of NAD(P)H since the stimulation of O2 consumption by reduced pyridine nucleotides is used as an indicator of the presence of a redox system in the plasma membrane. Oxygen consumption by intact GCP increased two- to threefold in the presence of NAD(P)H. The NAD(P)H-stimulation of O2 uptake was dependent on Mn(2+) and was stimulated 10- to 15-fold by salicylhydroxamic acid (SHAM). Catalase, cyanide and ascorbate, a superoxide scavenger, all individually inhibited the SHAM-stimulated O2 uptake. These are all characteristics of peroxidase activity although some of these features have been used to imply the presence of a redox system located in the plasma membrane. High levels of peroxidase activity (using guaiacol as a substrate) were also detected in the GCP and in the supernatant. The activity in the supernatant increased with time indicating that peroxidase was being excreted by the protoplasts. The properties of O2 uptake by the incubation medium after separation from the protoplasts were similar to those of the protoplast suspension. It is concluded that our observations can be more readily explained by peroxidase activity associated with the plasma membrane and secreted by the GCP than by the presence of a redox system in the plasma membrane of the protoplasts. PMID- 24221417 TI - Utilization of nitrate by bacteroids of Bradyrhizobium japonicum in the soybean root nodule. AB - Bacteroids of Bradyrhizobium japonicum strain CB1809, unlike CC705, do not have a high level of constitutive nitrate reductase (NR; EC 1.7.99.4) in the soybean (Glycine max. Merr.) nodule. Ex planta both strains have a high activity of NR when cultured on 5 mM nitrate at 2% O2 (v/v). Nitrite reductase (NiR) was active in cultured cells of bradyrhizobia, but activity with succinate as electron donor was not detected in freshly-isolated bacteroids. A low activity was measured with reduced methyl viologen. When bacteroids of CC705 were incubated with nitrate there was a rapid production of nitrite which resulted in repression of NR. Subsequently when NiR was induced, nitrite was utilized and NR activity recovered. Nitrate reductase was induced in bacteroids of strain CB1809 when they were incubated in-vitro with nitrate or nitrite. Increase in NR activity was prevented by rifampicin (10 MUg. ml(-1)) or chloramphenicol (50 MUg.ml(-1)). Nitrite-reductase activity in bacteroids of strain CB1809 was induced in parallel with NR. When nitrate was supplied to soybeans nodulated with strain CC705, nitrite was detected in nodule extracts prepared in aqueous media and it accumulated during storage (1 degrees C) and on further incubation at 25 degrees C. Nitrite was not detected in nodule extracts prepared in ethanol. Thus nitrite accumulation in nodule tissue appears to occur only after maceration and although bacteroids of some strains of B. japonicum have a high level of a constitutive NR, they do not appear to reduce nitrate in the nodule because this anion does not gain access to the bacteroid zone. Soybeans nodulated with strains CC705 and CB1809 were equally sensitive to nitrate inhibition of N2 fixation. PMID- 24221418 TI - The photoregulation of carotenoid biosynthesis in Aspergillus giganteus mut. alba. AB - Aspergillus giganteus mut. alba grown in darkness produced no carotenoids, but illuminated shake cultures accumulated 170 MUg.g(-1) dry weight of beta-carotene. Maximum carotenoid production occurred in white light of energy fluence rate of 50 W.m(-2). Blue light, but not red light, induced beta-carotene formation. A light induction period of 10 h was required for maximum beta-carotene synthesis, and this was attained 48 h after illumination. 5-Fluorouracil, actinomycin D and cycloheximide prevented photoinduction of carotenogenesis, indicating that photoregulation is at the transcriptional level. Comparisons of carotenogenic enzyme activities of light- and dark-grown cultures showed that phytoene synthetase, phytoene dehydrogenase and lycopene cyclase were totally photoinduced. Photoinduction of all three carotenogenic enzymes occurred after 12 h illumination. Squalene formation increased some four-fold upon illumination. PMID- 24221419 TI - Cellulose-microfibril-orienting mechanisms in plant cells walls. AB - A brief review is given of the changing views over the years, as knowledge of wall structure has developed, concerning the mechanism whereby cellulose chains may be oriented. This leads to an examination of current concepts, particularly those concerning microtubules. It is shown that none of the mechanisms suggested whereby microtubules might cause orientation of cellulose microfibrils is consistent with the known range of molecular architectures found in plant cell walls. It is further concluded that any mechanism which necessitates an indissoluble link between the plasmalemma and the cellulose-synthesising complex at the tip of a microfibril is unacceptable. A new proposal is presented in which it is speculated that both microtubules and microfibrils are oriented by a mechanism separate from both. It is shown that if two vectors are contemplated, one parallel to cell length and one at right angles, and a sensor exists on the plasmalemma surface which responds to changes in the vectors, then all known wall structures may be explained. The possible nature of the vectors and the sensor are considered. PMID- 24221420 TI - Physiological characterization of a plastidic signal required for nitrate-induced appearance of nitrate and nitrite reductases. AB - We compared the response of NO 3 (-) -induced nitrate-reductase (NR) and nitrite reductase (NIR) levels in virtually carotenoid-free far-red-light-grown mustard (Sinapis alba L.) cotyledons following a photooxidative treatment of the plastids. The cytosolic localization of NR and the plastidic localization of NIR were confirmed with this approach. Emphasis was on a plastidic factor previously postulated to be involved obligatorily in the transcriptional control of nuclear genes coding for proteins destined for the chloroplast. Photooxidative damage of the plastid would be to destroy the ability of the organelle to send off this signal. Dependency of NIR and NR induction by NO 3 (-) on the plastidic factor is described in detail, and it is concluded that requirement for the plastidic factor is relatively high in the case of NR while factor requirement to allow induction is low in the case of NIR. The data indicate that in the case of NIR the photooxidative damage done to the plastid also affects accumulation of the enzyme directly. Since this effect is absent in the case of cytosolic NR, induction of NR is a particularly suitable system for further molecular studies of the plastidic factor and its mode of action. PMID- 24221421 TI - Systemic induction of proteinase-inhibitor-II gene expression in potato plants by wounding. AB - The systemic induction of expression of the gene for proteinase inhibitor II after wounding different parts of potato (Solanum tuberosum L.) plants was analysed at the RNA level. Wounding of either leaves or tubers led to an induction of expression of this gene in non-wounded upper and lower leaves as well as in the upper stem segment, whereas no expression was observed in nonwounded roots or in the lower stem segment. The signal mediating the systemic induction in nonwounded tissue must therefore be able to move both acropetally and basipetally. The systemic wound response is specific for the expression of the proteinase-inhibitor-II gene as no influence was observed for the expression of genes encoding the small subunit of ribulose-1,5-bisphosphate carboxylase and the tuber storage protein patatin which were examined in parallel with the proteinase-inhibitor-II gene. PMID- 24221422 TI - Carnitine-acyltransferase activity of mitochondria from mung-bean hypocotyls. AB - Carnitine-acyltransferase activity assayed with acetyl-CoA, octanoyl-CoA, or palmitoyl-CoA is associated with the mitochondrial but not with the peroxisomes of mung-bean hypocotyls. Using mitochondria as an enzyme source, a half-maximal reaction rate is obtained with a palmitoyl-CoA concentration approximately twice that required with acetyl-CoA. In the presence of a saturating acetyl-CoA concentration the carnitine-acyltransferase activity is not enhanced by palmitoyl CoA as additional substrate. However, palmitoylcarnitine is formed in addition to acetylcarnitine, and the formation of acetylcarnitine is competitively inhibited by palmitoyl-CoA. It is concluded that the mitochondria of mung-bean hypocotyls possess a carnitine acyltransferase of broad substrate specificity with respect to the chainlength of the acyl-CoA and that the demonstration of a carnitine palmitoyltransferase activity in plant mitochondria does not indicate the presence of a specific carnitine long-chain acyltransferase. PMID- 24221423 TI - The role of calcium ions in phytochrome-controlled swelling of etiolated wheat (Triticum aestivum L.) protoplasts. AB - Protoplasts from dark-grown wheat (Triticum aestivum L.) maintained at a constant osmotic potential at 22 degrees C, were found to swell upon red irradiation (R) and the effect was negated by subsequent far-red light (FR), indicating phytochrome involvement. Swelling only occurred when Ca(2+) ions were present in the surrounding medium, or were added within 10 min after R. Furthermore, Mg(2+), Ba(2+) or K(+) could not replace this requirement for Ca(2+). The presence of K(+) did not enhance the Ca(2+)-dependent swelling response. When the Ca(2+) ionophore A 23187 was added to the medium, protoplasts swelled in the dark to the same extent as after R. Both the Ca(2+)-channelblocker Verapamil and La(3+) inhibited R-induced swelling. It is proposed that R causes the opening of Ca(2+) channels in the plasma membrane. Boyle-van't Hoff analyses of protoplast volume after R and FR are consistent with the conclusion that R irradiation causes changes in membrane properties. PMID- 24221424 TI - Synthesis of hydroxycinnamic acid esters of betacyanins via 1-O-acylglucosides of hydroxycinnamic acids by protein preparations from cell suspension cultures of Chenopodium rubrum and petals of Lampranthus sociorum. AB - Protein preparations from cell suspension cultures of Chenopodium rubrum L. and petals of Lampranthus sociorum (L.Bol.) N.E.Br. (Mes.C.L.Bol.) catalyzed the formation of acylated betacyanins, i.e. celosianin I and II (p-coumaroyl-and feruloylamaranthins) and lampranthin I and II (p-coumaroyl- and feruloylbetanins), from 1-O-(p-coumaroyl)-and 1-O-feruloyl-beta-glucoses as acyldonors and the respective acceptor molecules amaranthin (betanidin 5-O sophorobiuronic acid = betanidin 5-O-beta-[1"->2']-glucuronosyl-beta-glucoside) and betanin (betanidin 5-O-beta-glucoside). The enzymes involved could generally be classified as 1-O-hydroxycinnamoyl-beta-glucose:betanidinglycoside O hydroxycinnamoyltransferases (EC 2.3.1.-). PMID- 24221425 TI - Cellular basis of the effects of gibberellin and the pro gene on stem growth in tomato. AB - Tomato (Lycopersicon esculentum Mill.) plants homozygous for the mutant pro gene, exhibiting the distinctive procera phenotype, appeared virtually identical to gibberellic acid (GA3)-treated isogenic normal plants. The pro gene and GA3 caused analogous increases in internode length, and in the length and number of cells in the outer cell layers of each internode. Internode number was also increased by pro and GA3 over the period of the experiment. Despite their greater length, the internodes of GA3-treated and pro plants reached their final size within a time period similar to that of internodes of untreated normal plants. The pro mutant itself was responsive to GA3, especially in the seedling stage, but the proportional increase in height seen in the later stages of growth was less than that of normal plants. PMID- 24221426 TI - Apical localization of 1-aminocyclopropane-1-carboxylic acid and its conversion to ethylene in etiolated pea seedlings. AB - The biosynthetic basis for the high rates of ethylene production by the apical region of etiolated pea (Pisum sativum L.) seedlings was investigated. The ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) was quantified in extracts of various regions of seedlings by measuring isotopic dilution of a (2)H labelled internal standard using selected-ion-monitoring gas chromatography/mass spectrometry. The ACC levels in the apical hook and leaves were much higher than in the expanded internodes of the epicotyl. The capacity of excised tissue sections to convert exogenous ACC to ethylene was also much greater in the apical region, reflecting the distribution of soluble protein in the epicotyl. PMID- 24221427 TI - Characterization and localization of fusicoccin-binding sites in leaf tissues of Vicia faba L. probed with a novel radioligand. AB - Tritiated 9'-nor-fusicoccin-8'-alcohol provides a highly bioactive radioligand of high specific activity which is easily prepared by oxidation of fusicoccin and subsequent reduction with tritiated sodium borohydride. Using this radioligand, we have identified and characterized a selective binding site for fusicoccin (Ka for [(3)H]-9'-nor-fusicoccin-8'-alcohol=0.20.10(9) M(-1); Ka, apparent for fusicoccin=0.21.10(9) M(-1)) located at the plasmalemma of Vicia faba leaf tissue. The site is thermolabile, readily degraded by trypsin and located at the apoplastic face of the plasmalemma based on results obtained using right-side-out plasmalemma vesicles prepared by aqueous two-phase partitioning and macromolecular fusicoccin-derivatives. The binding-protein is present in guard cells of Vicia faba, as shown by the use of purified guard-cell protoplasts. PMID- 24221428 TI - Osmotic regulation of starch synthesis in potato tubers? AB - Using potato (Solanum tuberosum L.) tuber discs incubated in a range of mannitol concentrations it has been demonstrated that both sucrose uptake and the conversion of sucrose to starch are sensitive to the osmotic environment of the storage cells. Starch synthesis was optimised at 300 mM but declined sharply at both lower and higher osmotic concentrations. The decline in starch synthesis on either side of optimum was not proportional to the change in mannitol concentration, indicating different inhibitory mechanisms under low and high osmotica. The fraction of the total sucrose converted to starch i.e. the partitioning between sucrose and starch, was also influenced by osmotic environment. The amount of soluble material taken up by the storage cells, but not converted to starch, was maintained under mannitol concentrations (300-400 mM) which inhibited starch synthesis, indicating that sucrose uptake continued during declining starch synthesis. At mannitol concentrations above 400 mM, sucrose uptake was greatly enhanced but no significant change in starch synthesis occurred. PMID- 24221429 TI - Development of plant cuticles: fine structure and cutin composition of Clivia miniata Reg. leaves. AB - The fine structure and monomeric composition of the ester-cutin fraction (susceptible to BF3/CH3OH transesterification) of the adaxial leaf cuticle of Clivia miniata Reg. were studied in relation to leaf and cuticle development. Clivia leaves grow at their base such that cuticle and tissues increase in age from the base to the tip. The zone of maximum growth (cell expansion) was located between 1 and 4 cm from the base. During cell expansion, the projected surface area of the upper epidermal cells increased by a factor of nine. In the growth region the cuticle consists mainly of a polylamellate cuticle proper of 100-250 nm thickness. After cell expansion has ceased both the outer epidermal wall and the cuticle increase in thickness. Thickening of the cuticle is accomplished by interposition of a cuticular layer between the cuticle proper and the cell wall. The cuticular layer exhibits a reticulate fine structure and contributes most of the total mass of the cuticle at positions above 6 cm from the leaf base. The composition of ester cutin changed with the age of cuticles. In depolymerisates from young cuticles, 26 different monomers could be detected whereas in older ones their number decreased to 13. At all developmental stages, 9,16-/10,16 dihydroxyhexadecanoic acid (positional isomers not separated), 18-hydroxy-9 octadecenoic acid, 9,10,18-trihydroxyoctadecanoic acid and 9,10-epoxy-18 hydroxyoctadecanoic acid were most frequent with the epoxy alkanoic acid clearly predominating (47% at 16 cm). The results are discussed as to (i) the age dependence of cutin composition, (ii) the relationship between fine structure and composition, (iii) the composition of the cuticle proper, the cuticular layer and the non-depolymerizable cutin fraction, and (iv) the polymeric structure of cutin. PMID- 24221430 TI - Molecular markers (RFLPs and HSPs) for the genetic dissection of thermotolerance in maize. AB - Cellular membrane stability (CMS) is a physiological index widely used to evaluate thermostability in plants. The genetic basis of the character has been studied following two different approaches: restriction fragment length polymorphism (RFLP) analysis, and the effects of segregating heat shock protein (HSP) loci. RFLP analysis was based on a set of recombinant inbreds derived from the T32 * CM37 F1 hybrid and characterized for about 200 RFLP loci. Heritability of CMS estimated by standard quantitative analysis was 0.73. Regression analysis of CMS on RFLPs detected a minimum number of six quantitative trait loci (QTL) accounting for 53% of the genetic variability. The analysis of the matrices of correlation between RFLP loci, either within or between chromosomes, indicates that no false assignment was produced by this analysis. The effect of HSPs on the variability of the CMS was tested for a low-molecular-weight peptide (HSP-17) showing presence-absence of segregation in the B73 * Pa33 F2 population. Although the genetic variability of the character was very high (h (2)=0.58) the effect of HSP-17 was not significant, indicating either that the polypeptide is not involved in the determination of the character or that its effect is not statistically detectable. PMID- 24221431 TI - Crossbreeding effects after long-term selection for purebred performance: a model experiment with mice : 1. Performance of F1 crosses. AB - The influence of purebred selection on the combining abilities of five lines of mice was examined. Two replicated testcross diallels were made after 10 and 20 generations of purebred selection for litter size, weaning weight, weight gain, and feed efficiency. Average direct genetic effects were of major importance, followed by average maternal genetic effects. In all of the replications, between two and four out of ten crosses showed significant heterosis. Heterosis ranged from 0 to 38% in litter size, from 0 to 20% in weaning weight, from -11 to 11% in weight gain, and from -8 to 17% in feed efficiency. For litter size and weaning weight, heterosis estimates increased between 80 and 100% from generation 10 to 20. Weight gain and feed efficiency showed decreasing heterosis with partly negative estimates in the second diallel. Combinations exhibiting significant heterosis varied between replicates and between the two diallels. PMID- 24221432 TI - Associations of genes encoding allozymes peroxidase and superoxide dismutase in poplar and spruce species. AB - Isozymes of peroxidase (PER) and superoxide dismutase (SOD) were analyzed in vegetative buds or very young leaves of seven species and two interspecific hybrids of Populus, in progenies of seven controlled crosses of three Populus species, and in needles of five Picea species and one putative hybrid. One to three PER, and one or two SOD zones of activity were observed. Electrophoretic mobility (EM) and banding phenotypes of isozymes of one PER locus were identical to those of one SOD locus in vegetative buds of five Populus species and hybrid. In leaves of the four Populus species and hybrid and progenies of controlled crosses, EM and phenotypes of isozymes of two PER loci were identical to those of two SOD loci. In Picea species, EM of isozymes of the only SOD locus was somewhat similar but not identical to that of one PER locus, and isozyme phenotypes of all individuals at the SOD locus were not identical to those at a PER locus. Chi square tests verified the single-gene Mendelian control of the segregating allozyme variants at each of Per-L1 and Sod-1 in the three Populus species. The results of joint two-locus segregation tests indicated a very tight linkage and no recombination between Per-L1 and Sod-1 in three Populus species. Genes coding for isozymes of one or two PER loci are either presumably the same as, or very tightly linked to, the genes coding for isozymes of one or two SOD loci in the Populus species. PMID- 24221433 TI - Analysis of the resistance of Aegilops squarrosa to the wheatgrass mildew fungus by using the gene-for-gene reationship. AB - Pm10 and Pm15, resistance genes to Erysiphe graminis f. sp. agropyri, are located on the D genome of common wheat. It was determined whether or not they were carried by existing lines of the D genome donor, Aegilops squarrosa, using the gene-for-gene relationship. Two lines of Ae. squarrosa tested (one was var. meyeri and the other was var. anathera) were susceptible to culture Tk-1 of E. graminis f. sp. tritici and were highly resistant to culture Ak-1 of E. graminis f. sp. agropyri. The two lines were inoculated with an F1 population derived from the cross Ak-1 * Tk-1. Comparative analyses of the segregation patterns revealed that Ppm10 and Ppm15, avirulence genes corresponding to Pm10 and Pm15, respectively, are involved in the avirulence of Ak-1 on var. meyeri and var. anathera, respectively. According to the gene-for-gene relationship, var. meyeri and var. anathera were inferred to carry Pm10 and Pm15, respectively. Analysis with a synthetic hexaploid confirmed the inference. PMID- 24221434 TI - Isolation and characterization of two middle repetitive DNA sequences of nuclear tobacco genome. AB - Two DNA sequences, R8.1 and R8.3, representing two distinct classes of tobacco genomic repeated DNA, were cloned and characterized by Southern blot analysis. Both R8.1 and R8.3 were found to be homologous to the Nicotiana tomentosiformis component of the allotetraploid Nicotiana tabacum genome, and each of them represents about 0.3% of nuclear DNA. The R8.1 and R8.3 differ in the mode of distribution in chromosomes, as revealed by in situ DNA/DNA hybridization. PMID- 24221435 TI - Genetic variability of the wild incompatibility alleles of the tetrapolar basidiomycete Agrocybe aegerita. AB - The variability of the sexual incompatibility genes of Agrocybe aegerita was investigated in the homokaryotic progeny of 13 wild dikaryotic strains from five distinct European geographic origins. Results of mating tests allowed identification of 18 A alleles and 16 B alleles out of a possible 26 different alleles for each in the sample. The determination and the comparison by a contingency chi (2) test of the frequencies of allele replications between intra- and interregional matings showed no departure from a random distribution of incompatibility alleles. The allelic series estimated for the incompatibility genes of the entire population of A. aegerita, 30 A and 25 B aleles, are significantly less extensive than those already hypothesized for other tetrapolar hymenomycetes. However, the low variability of incompatibility genes has little effect on the outbreeding efficiency (92.6%) of this mushroom. The low variability of the incompatibility alleles and the apparent absence of intrafactorial recombination could relate to a single-locus structure of the incompatibility genes in A. aegerita. PMID- 24221436 TI - Phylogenetic relationships among cultivated Allium species from restriction enzyme analysis of the chloroplast genome. AB - The genus Allium contains many economically important species, including the bulb onion, chive, garlic, Japanese bunching onion, and leek. Phylogenetic relationships among the cultivated alliums are not well understood, and taxonomic classifications are based on relatively few morphological characters. Chloroplast DNA is highly conserved and useful in determining phylogenetic relationships. The size of the chloroplast genome of Allium cepa was estimated at 140 kb and restriction enzyme sites were mapped for KpnI, PstI, PvuII, SalI, XbaI, and XhoI. Variability at restriction enzyme sites in the chloroplast DNA was studied for at least three accessions of each of six cultivated, old-world Allium species. Of 189 restriction enzyme sites detected with 12 enzymes, 15 mutations were identified and used to estimate phylogenetic relationships. Cladistic analysis based on Wagner and Dollo parsimony resulted in a single, most-parsimonious tree of 16 steps and supported division of the species into sections. Allium species in section Porrum were distinguished from species in sections Cepa and Phyllodolon. Two species in section Rhiziridium, A. schoenoprasum and A. tuberosum, differed by five mutations and were placed in separate lineages. Allium cepa and A. fistulosum shared the loss of a restriction enzyme site and were phylogenetically closer to each other than to A. schoenoprasum. This study demonstrates the usefulness of restriction enzyme site analysis of the chloroplast genome in the elucidation of phylogenetic relationships in Allium. PMID- 24221437 TI - Cytology and morphology of the amphiploid Hordeum chilense (4x) * Aegilops squarrosa (4x). AB - The intergeneric amphiploid Hordeum chilense * Aegilops squarrosa has been synthesized. The amphiploid plants have the expected chromosome number of 28. The average meiotic chromosome pairing was 12.48 bivalents + 3.04 univalents. The morphology of the amphiploid resembles that of the Aegilops parent. Nucleoli from both H. chilense and A. squarrosa are expressed in the amphiploid. Neither chromosome instability nor homoeologous pairing was found. The amphiploid is fertile and vigorous. PMID- 24221438 TI - Cotransformation and differential expression of introduced genes into potato (Solanum tuberosum L.) cv Bintje. AB - The Dutch potato cultivar Bintje has been transformed by Agrobacterium strain LBA1060KG, which contains two plasmids carrying three different DNAs (TL- and TR DNA on the Agrobacterium rhizogenes plasmid and TKG-DNA on the pBI121 plasmid). Several transformed root clones were obtained after transformation of leaf, stem, and tuber segments, and plants were then regenerated from these root clones. The expression of the various marker genes [rol, opine, beta-glucuronidase (GUS), and neomycin phosphotransferase (NPTII)] was determined in several root clones and in regenerated plants. The selection of vigorously growing root clones was as efficient as selection for kanamycin resistance. In spite of the location of NPTII and GUS genes on the same T-DNA, 17% of the root clones did not show GUS activity. Nevertheless, Southern blot analysis showed that these root clones contained at least three copies of the GUS gene. Sixty-four per cent of the root clones contained opines. The expression of these genes, however, was negatively correlated with plant regeneration capacity and normal plant development. The differential expression of the marker genes in the transgenic potato tissues is discussed. PMID- 24221439 TI - Transformation of Brassica oleracea with an S-locus gene from B. campestris changes the self-incompatibility phenotype. AB - An SLG gene derived from the S-locus and encoding and S-locus-specific glycoprotein of Brassica campestris L. was introduced via Agrobacterium-mediated transformation into B. oleracea L. A self-incompatible hybrid and another with partial self-compatibility were used as recipients. The transgenic plants were altered in their pollen-stigma interaction and were fully compatible upon self pollination. Reciprocal crosses between the transgenic plants and untransformed control plants indicated that the stigma reaction was changed in one recipient strain while the pollen reaction was altered in the other. Due to interspecific incompatibility, we could not demonstrate whether or not the introduced SLG gene confers a new allelic specificity in the transgenic plants. Our results show that the introduced SLG gene perturbs the self-incompatibility phenotype of stigma and pollen. PMID- 24221440 TI - Cloning of the coat protein gene from beet necrotic yellow vein virus and its expression in sugar beet hairy roots. AB - Expression of the beet necrotic yellow vein virus (BNYVV) coat protein (CP) gene in transgenic sugar beet hairy roots was accomplished as a step towards CP mediated virus resistance. A cDNA for the CP gene and its 5' terminal untranslated leader sequence was prepared from BNYVV RNA, using two oligodeoxynucleotides to prime the synthesis of both strands. Second-strand synthesis and amplification of the cDNA were done by Taq DNA polymerase chain reactions. Run-off transcripts of the cloned cDNA sequence were obtained and translated in vitro, yielding immunoreactive CP. A binary vector construction containing the CP gene under the control of the 35S promoter of cauliflower mosaic virus was prepared and used for Agrobacterium rhizogenes-mediated transformation of sugar beet tissue. Stable integration and expression of the CP gene in sugar beet hairy roots was demonstrated by Southern, Northern, and Western blot analysis, respectively. PMID- 24221441 TI - Chloroplast DNA restriction fragment length polymorphisms (RFLPs) in Musa species. AB - Taxonomic and phylogenetic determinations within the genus Musa are established using a numerical, morphology-based scoring system. However, within this system, the classification and relationships of some types are disputed. The application of chloroplast DNA (cpDNA) restriction fragment length polymorphism (RFLP) analysis to Musa taxonomy provided valuable, supplemental information about the classification of, and relationships between, Musa species and subspecies. Whole cell DNA was extracted from lyophilized Musa leaf-blade tissue and digested with various restriction enzymes, Southern blotted onto nylon membranes, and probed using radioactively labeled heterologous orchid cpDNA fragments. Phylogenies were inferred from cpDNA RFLP patterns using PAUP software. The relationships between most species examined were as expected; however, some species (M. beccarii and M. basjoo) did not conform to the conventional morphology-based phylogeny. PMID- 24221442 TI - Water-soluble proteins of mature barley endosperm: genetic control, polymorphism, and linkage with beta-amylase and spring/winter habit. AB - Water-soluble proteins (WSP-2 and WSP-3) and beta-amylase (beta-AMY-1) were extracted from mature endosperms of 44 spring and 39 winter barley genotypes. The protein and enzyme isoforms were separated in isoelectric focusing gels with a pH gradient of 4-6.5. The Wsp-3 and beta-Amy-1 loci were located to chromosomes 4H using the wheat/barley chromosome addition lines. Segregation analysis of F2 and doubled haploid populations showed Wsp-2 and beta-Amy-1 to be tightly linked, with a map distance of 11 cMorgans. Isoforms of WSP-2 possessed similar pIs to that of WSP-3 and overlapping bands were observed in the gels. These bands segregated independently in F2 and doubled haploid populations, implying two unlinked genes. All three loci were found to be polymorphic: two alleles were detected at the Wsp-2 locus, three at Wsp-3 and two at beta-Amy-1. The frequency of alleles at all three loci was found to be different in winter and spring genotypes. Spring genotypes possessed a wider range of phenotypes than winter genotypes. Spring and winter genotypes could be distinguished on the basis of WSP 3 and beta- AMY-1 phenotypes. The linkage between Wsp-3 and beta-Amy-1 loci and genes controlling spring/winter habit on chromosome 4H is discussed. It is concluded that Wsp-3 and beta-Amy-1 can be used as genetic markers for spring/winter habit in barley genetic research and breeding. PMID- 24221443 TI - Characterization of pearl millet mitochondrial DNA fragments rearranged by reversion from cytoplasmic male sterility to fertility. AB - Cloned pearl millet [Pennisetum glaucum (L.) R. Br.] mitochondrial (mt) DNA fragments rearranged by spontaneous reversion from cytoplasmic male sterility (cms) to fertility were characterized by restriction mapping, hybridization with maize mt genes, and transcription analyses. The clones characterized were a 4.7 kb fragment found only in the male-sterile cytoplasm and lost upon reversion to fertility, a 10.9-kb fragment found in all cytoplasms and not changed by reversion, a 13.6-kb fragment found in the male-sterile and -fertile normal cytoplasms and lost in seven of the eight revertants studied, and a 9.7-kb fragment not found in the male-sterile cytoplasm but produced by reversion from male sterility to fertility. The restriction maps verified that the four cloned pearl millet fragments contained two sets of repeated sequences, one on the 4.7-, 10.9-, and 13.6-kb fragments, the other on the 13.6- and 9.7-kb fragments. The rrn18, rrn5, and coxI genes were located in the repeated regions of the 4.7-, 10.9-, and 13.6-kb cloned fragments. The correlation of reversion (eight independent events) with the loss of fragments containing the rrn18, rrn5, and coxI genes suggests that those lost fragments and their gene content could be responsible for the expression of cms. Transcriptional analyses using both Northern blots and end-labeled mtRNA probes verified that transcripts homologous to the rrn18 and coxI genes were present in pearl millet total mtRNA. However, no transcript differences were detected among cms, revertant, and fertile normal cytoplasms, suggesting that the reversion process involves mutational changes that may not affect transcript size. Transcript analyses indicated that the 10.9 kb clone contained an unidentified gene on the end opposite the rrn18 gene; however, since it was present in all cytoplasms, it is not believed to be involved in cms. PMID- 24221444 TI - Pisum lipoxygenase genes. AB - The copy number, genomic arrangement and linkage relationships of two classes of lipoxygenase gene have been investigated in Pisum(pea) lines. Each of the two classes contained two to three members in P. sativum lines. RFLPs associated with genomic fragments containing the 5' sequences of one gene class permitted its correlation in genetical analyses with a lipoxygenase locus on linkage group 4, which was previously identified through polypeptide variation. Genetical analyses of RFLPs associated with other fragments identified by low- and medium-stringency hybridization to lipoxygenase cDNAs indicate the existence of other unlinked lipoxygenase gene loci. PMID- 24221445 TI - DNA restriction fragment length polymorphisms correlate with isozyme diversity in Phaseolus vulgaris L. AB - Genetic variation in Phaseolus vulgaris L. (P. vulgaris) was investigated at the isozyme and DNA levels. We constructed a library of size-selected Pst I clones of P. vulgaris nuclear DNA. Clones from this library were used to examine 14 P. vulgaris accessions for restriction fragment length polymorphisms (RFLPs). DNAs from each accession were analyzed with three restriction enzymes and 18 single copy probes. The same accessions were also examined for variability at 16 isozyme loci. Accessions included four representatives of the T phaseolin group and five representatives each of the C and S phaseolin groups. One member of the S group (the breeding line XR-235-1-1) was derived from a cross between P. vulgaris and P. coccineus. Isozymes and RFLPs revealed very similar patterns of genetic variation. Little variation was observed among accessions with C and T phaseolin types or among those with the S phaseolin type. However, both isozyme and RFLP data grouped accessions with S phaseolin separately from those accessions with C or T phaseolin. The highest degree of polymorphism was observed between XR-235-1 1 and members of the C/T group. RFLP markers will supplement isozymes, increasing the number of polymorphic loci that can be analyzed in breeding, genetic, and evolutionary studies of Phaseolus. PMID- 24221446 TI - Nucleotide sequence and transcriptional analysis of a mitochondrial plasmid from a cytoplasmic male-sterile line of sunflower. AB - A mitochondrial plasmid of 1,939 bp (P2) from a cytoplasmic male-sterile line of sunflower has been cloned and sequenced. It presents 437 bp of near-perfect homology to the 1.4-kb mitochondrial plasmid P1 from sunflower. Sequences homologous to P2 were found in nuclear DNA. P2 was transcribed into a major 980 nucleotide (nt) RNA molecule and two minor transcripts of 570 and 520 nt. They were all transcribed from the same strand and within the region nonhomologous to P1. A single 5' boundary and three 3' termini were determined for P2 transcripts. The 5' end is similar to a consensus sequence for plant mitochondrial genes. No evidence of translation products can be provided. PMID- 24221447 TI - Rapid hybridization-based assays for identification by DNA probes of male-sterile and male-fertile cytoplasms of the sugar beet Beta vulgaris L. AB - Methods are described whereby hybridization of mitochondrial (mt) DNA with different DNA probes can definitely distinguish male-fertile and and male-sterile (cms) cytoplasms of sugar beet Beta vulgaris L. We have developed two types of miniassays. (1) Comparative methods requiring the isolation and restriction of total cellular DNA, hybridization with cloned mtDNA fragments from either fertile or male-sterile cytoplasms, and comparison of the hybridization patterns to the fertile-and sterile-specific patterns of mtDNA of sugar beet for the given mtDNA probe. For these analyses, we routinely used 1 g of plant material to determine the type of cytoplasm. (2) Noncomparative ("plus-minus") methods requiring neither the isolation of pure DNA nor restriction, electrophoresis, or Southern blotting. Instead, alkaline-SDS plant extracts from as little as 50 mg of plant material were dot-blotted and hybridized with fertile-specific (mitochondrial minicircular DNA) and/or cms-specific probes (consisting of a 2.3-kb mtDNA sequence exclusively occurring in the cms cytoplasm). The assays are simple to perform, give definitive results, are nonde-structive to the plants, and may be used in mass screening of sugar beet populations for hybrid production or in in vitro culture processes. PMID- 24221448 TI - Expected utility maximization and selection of stable plant cultivars. AB - In most plant breeding programs, selection of the best commercially suitable cultivars for a target group of environments is based on information obtained from evaluation trials cultivated in a sample of environments. Information on the performance of cultivars collected in a sample of environments can only be approximate and, consequently, selection of the best cultivar involves choosing among cultivars that respond uncertainly in many environments. The agronomic and/or economic value of a cultivar across environments may be considered the general or overall utility of the cultivar. Data from a sample of environments therefore provides only an estimate of any cultivar's overall utility, with the overall goal of selection among all cultivars being the maximization of the expected utility. Within this frame-work, expected utility maximization, an approach to decision making that has been well developed in the disciplines of economics and statistics, can assist the plant breeder in making such decisions. This research was initiated (1) to determine how expected utility maximization might be used to develop indices that are useful for selecting broadly adapted plant cultivars, and (2) to determine how the breeder's preferences might affect choice of the best cultivar. The data used in this research were from USDA Regional Soybean Tests. The results indicated that expected utility maximization, which explicitly incorporates into the selection rule the plant breeder's preferences regarding stability, can be a useful aid in the selection of stable plant cultivars. PMID- 24221449 TI - Production, morphology, and cytogenetics of Triticum aestivum (L.) Thell * Elymus scabrus (R. Br.) Love intergeneric hybrids obtained by in ovulo embryo culture. AB - Intergeneric hybrids were produced between common wheat, Triticum aestivum (2n=6x=42, AABBDD), and an apomictic Triticeae species, Elymus scabrus (syn. Agropyron scabrum) (2n=6x=42, HHSSSS), the first successful report of this cross. Nine tiny, underdeveloped, and structureless embryos were obtained in vitro only by in ovulo embryo culture at 4 days after pollination, which gave rise to five mature hybrid plants. All the hybrid plants were vigorous and possessed a phenotype intermediate to the two parents. There were 2n=6x=42 (ABDHSS) somatic chromosomes in the hybrids. There was little or no homology between the parental genomes, as shown by an overall meiotic chromosome association of 32.83 I + 4.08 rod II + 0.21 ring II + 0.18 III + 0.02 IV. The hybrids were completely sterile and so far backcrosses to wheat parent have not been successful. Alternate approaches to induce gene transfer(s) from E. scabrus to wheat are being attempted. PMID- 24221450 TI - Increase in prophylaxis of glucocorticoid-induced osteoporosis by pharmacist feedback: a randomised controlled trial. AB - The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low. INTRODUCTION: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline. METHODS: This randomised controlled trial included 695 patients who were dispensed >=675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D). RESULTS: The group assigned to the intervention was slightly younger than the control group (68.7 +/- 15.4 vs. 65.9 +/- 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients >=70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered. CONCLUSION: This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population, but there was an increase in men and the elderly. However, the proportion of GIOP-treated patients remained low. PMID- 24221451 TI - Prospective evaluation of renal function, serum vitamin D level, and risk of fall and fracture in community-dwelling elderly subjects. AB - SUMMARY: This prospective study in elderly showed that kidney function plays a minor role in explaining the high prevalence of vitamin D deficiency seen in noninstitutionalized elderly subjects. However, 25-hydroxyvitamin D levels were clearly inversely associated with risk for first fall, which was especially seen in subjects with calcium levels above median. INTRODUCTION: Few prospective studies in elderly exist that have investigated the association of renal dysfunction and vitamin D status on risk of falls. The aim of this study is to evaluate the association of renal function with 25-hydroxyvitamin D (25-OH-D) levels and, secondly, to assess the role of both factors on the risk of falls and subsequent bone fractures. METHODS: This is a prospective population-based cohort study among noninstitutionalized elderly subjects during a 1-year follow-up. 25 OH-D levels and renal function were estimated, the latter by cystatin C-based equations. Information on falls was assessed prospectively. RESULTS: Overall, 1,385 subjects aged 65 and older were included in the study (mean age 75.6 years), of whom 9.2 % had a 25-OH-D serum level above 75 nmol/L (US units 30 ng/mL); 41.4 %, between 50 and 75 nmol/L (US units 20 to 29 ng/mL, insufficiency); and 49.4 %, <50 nmol/L (US units <20 ng/mL, deficiency). We found no association of chronic kidney disease with risk of first fall. In contrast, 25 OH-D serum categories were clearly associated with risk of first fall and we found evidence of effect modification with calcium levels. In the group with a calcium level above the median (>= 9.6 mg/dL), subjects with 25-OH-D serum level between 50 and 75 nmol/L and with concentrations <50 nmol/L had a hazard rate ratio (HRR) of 1.75 (1.03-2.87) and 1.93 (1.10-3.37) for risk of first fall. 25 OH-D serum levels were also associated with several markers of inflammation and hemodynamic stress. CONCLUSIONS: We demonstrated an association of 25-OH-D serum levels and risk of first fall, which was especially evident in subjects with serum calcium in upper normal, independent of renal function. PMID- 24221452 TI - Regional depth-specific subchondral bone density measures in osteoarthritic and normal patellae: in vivo precision and preliminary comparisons. AB - SUMMARY: Computed tomography-based depth-specific image processing is able to precisely identify regional differences between healthy patellae and patellae with osteoarthritis. INTRODUCTION: This study aims to assess the precision errors and potential differences in regional, depth-specific subchondral bone mineral density (BMD) in normal and osteoarthritic (OA) human patellae in vivo using CT based density analyses. METHODS: Fourteen participants (2 men and 12 women; mean age, 51.4; SD, 11.8 years) were scanned using clinical quantitative CT (QCT) three times over 2 days. Participants were categorized as either normal (n = 7) or exhibiting radiographic OA (n = 7). Average subchondral BMD was assessed at three depths relative to the subchondral surface. Regional BMD analysis included: total lateral facet BMD, total medial facet BMD, and superior/middle/inferior BMD of lateral and medial facets at normalized depths of 0-2.5, 2.5-5, and 5-7.5 mm from the subchondral surface. We assessed precision using root mean square coefficients of variation (CV%). We evaluated differences between OA and normal BMD by (1) calculating percentage differences between the groups (in relation to normal BMD) (2) relating percentage differences to respective CV% errors and (3) determining effect sizes using Cohen's d. RESULTS: Root mean square CV% precision errors ranged from 1.1 to 5.9 %. Percentage differences between OA and normal BMD varied from -1.6 to -30.1 % (BMD lower in OA patellae). In relation to precision errors, percentage differences were, on average, 5.5* greater than CV% errors. Cohen's d effect sizes ranged from -1.7 to -0.1. Largest differences were noted at depths of 2.5-5 and 5-7.5 mm from the subchondral surface. CONCLUSIONS: Patellar subchondral BMD measures were precise (average CV%, <=3 %). This region- and depth-specific CT-based imaging tool characterized regional standardized BMD differences between normal and OA patellae in vivo. PMID- 24221454 TI - [Pneumococcus vaccination in immunosuppressed patients: current recommendations]. PMID- 24221455 TI - Duodenal exclusion devices: promising tools in treating obesity and type 2 diabetes. PMID- 24221453 TI - Vertebral deformities and fractures are associated with MRI and pQCT measures obtained at the distal tibia and radius of postmenopausal women. AB - SUMMARY: We investigated the association of postmenopausal vertebral deformities and fractures with bone parameters derived from distal extremities using MRI and pQCT. Distal extremity measures showed variable degrees of association with vertebral deformities and fractures, highlighting the systemic nature of postmenopausal bone loss. INTRODUCTION: Prevalent vertebral deformities and fractures are known to predict incident further fractures. However, the association of distal extremity measures and vertebral deformities in postmenopausal women has not been fully established. METHODS: This study involved 98 postmenopausal women (age range 60-88 years, mean 70 years) with DXA BMD T scores at either the hip or spine in the range of -1.5 to -3.5. Wedge, biconcavity, and crush deformities were computed on the basis of spine MRI. Vertebral fractures were assessed using Eastell's criterion. Distal tibia and radius stiffness was computed using MRI-based finite element analysis. BMD at the distal extremities were obtained using pQCT. RESULTS: Several distal extremity MRI and pQCT measures showed negative association with vertebral deformity on the basis of single parameter correlation (r up to 0.67) and two-parameter regression (r up to 0.76) models involving MRI stiffness and pQCT BMD. Subjects who had at least one prevalent vertebral fracture showed decreased MRI stiffness (up to 17.9 %) and pQCT density (up to 34.2 %) at the distal extremities compared to the non fracture group. DXA lumbar spine BMD T-score was not associated with vertebral deformities. CONCLUSIONS: The association between vertebral deformities and distal extremity measures supports the notion of postmenopausal osteoporosis as a systemic phenomenon. PMID- 24221456 TI - Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Acid-suppressive medications, particularly proton pump inhibitors (PPIs), may decrease the risk of oesophageal adenocarcinoma (OAC) in patients with Barrett's oesophagus (BO). We performed a systematic review with meta-analysis of studies evaluating the association between acid-suppressive medications (PPIs and histamine receptor antagonists (H2RAs)) and risk of OAC or high-grade dysplasia (BO-HGD) in patients with BO. METHODS: We performed a systematic search of multiple electronic databases and conference proceedings up to June 2013 to identify studies reporting the association between use of acid suppressive medications and risk of OAC and/or BO-HGD in patients with BO. Summary ORs with 95% CIs were estimated. RESULTS: We identified seven observational studies (2813 patients with BO, 317 cases of OAC or BO-HGD, 84.4% PPI users). On meta-analysis, PPI use was associated with a 71% reduction in risk of OAC and/or BO-HGD in patients with BO (adjusted OR 0.29; 95% CI 0.12 to 0.79). There was a trend towards a dose-response relationship with PPI use for >2-3 years protective against OAC or BO-HGD (three studies; PPI use >2-3 years vs <2-3 years: OR 0.45 (95% CI 0.19 to 1.06) vs 1.09 (0.47 to 2.56)). Considerable heterogeneity was observed. Two studies reported the association between H2RA use and risk of OAC and/or BO-HGD (1352 patients with BO, 156 cases of OAC, 25.4% on H2RAs), and both studies did not show a significant effect. CONCLUSIONS: Based on meta-analysis of observational studies, the use of PPIs is associated with a decreased risk of OAC and/or BO-HGD in patients with BO. None of the studies showed an increased risk of OAC. PPI use should be considered in BO, and chemopreventive trials of PPIs in patients with BO are warranted. PMID- 24221457 TI - What is the role for bisphosphonates in IBD? PMID- 24221458 TI - p21Waf1/Cip1 revisited: oncogenic function in hepatocellular carcinoma. PMID- 24221459 TI - Controversies in the management of Irvine-Gass syndrome. PMID- 24221460 TI - Electronic health records: future clinical applications. Part 2 in a two-part series. AB - In this second installment of his two-part column on electronic health records, Dr. Robert Wang addresses the ways in which EHRs can enhance clinical operations. He explores how to improve revenue and efficiency by enlisting an EHR system to facilitate charting, coding, ICD-10 implementation, patient flow, and meaningful use submission. PMID- 24221461 TI - Comparison of fundus autofluorescence between fundus camera and confocal scanning laser ophthalmoscope-based systems. AB - BACKGROUND AND OBJECTIVE: To compare fundus autofluorescence (FAF) imaging via fundus camera (FC) and confocal scanning laser ophthalmoscope (cSLO). PATIENTS AND METHODS: FAF images were obtained with a digital FC (530 to 580 nm excitation) and a cSLO (488 nm excitation). Two authors evaluated correlation of autofluorescence pattern, atrophic lesion size, and image quality between the two devices. RESULTS: In 120 eyes, the autofluorescence pattern correlated in 86% of lesions. By lesion subtype, correlation rates were 100% in hemorrhage, 97% in geographic atrophy, 82% in flecks, 75% in drusen, 70% in exudates, 67% in pigment epithelial detachment, 50% in fibrous scars, and 33% in macular hole. The mean lesion size in geographic atrophy was 4.57 +/- 2.3 mm(2) via cSLO and 3.81 +/- 1.94 mm(2) via FC (P < .0001). Image quality favored cSLO in 71 eyes. CONCLUSION: FAF images were highly correlated between the FC and cSLO. Differences between the two devices revealed contrasts. Multiple image capture and confocal optics yielded higher image contrast with the cSLO, although acquisition and exposure time was longer. PMID- 24221462 TI - Serum erythropoietin, insulin-like growth factor 1, and vascular endothelial growth factor in etiopathogenesis of retinopathy of prematurity. AB - BACKGROUND AND OBJECTIVE: The role of growth factors in the pathogenesis of retinopathy of prematurity (ROP) is known. To better understand this issue, the authors investigated vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and erythropoietin (EPO) levels in the cord blood of premature newborns. PATIENTS AND METHODS: IGF-1, VEGF, and EPO levels were measured in cord blood samples obtained from 93 infants less than 32 weeks of gestational age at birth, and their predictive value in the development of ROP was investigated. RESULTS: The mean birth age and mean birth weight were 32.2 +/- 1.5 weeks and 1,678 +/- 326 g, respectively, in infants without ROP and 29.6 +/- 2.3 weeks and 1,384 +/- 343 g, respectively, in infants with ROP. Multivariate logistic regression analysis showed that only the gestational age and the serum VEGF at birth were independently associated with the risk of developing ROP (P = .002, Exp[B] = 0.514, CI = 95%: 0.341-0.775; P = .028, Exp[B] = 0.999, CI = 95%: 0.997-1.00). CONCLUSION: Serum VEGF levels at birth were lower in infants who later developed ROP. This may have a predictive value for ROP and contribute to the pathogenesis, because affected infants may be more susceptible to extrauterine hyperoxic insult. PMID- 24221463 TI - Assessment of novel guarded needle to increase patient comfort and decrease injection time during intravitreal injection. AB - BACKGROUND AND OBJECTIVE: To determine whether a novel guarded 33-gauge injection device can make the intravitreal injection procedure faster and more comfortable for patients. PATIENTS AND METHODS: Single-center, prospective, randomized interventional study. Seventy participants receiving bilateral injections on the same day had one eye injected with the 33-gauge injection device without a speculum and the other eye injected with a standard 30-gauge needle using a speculum. Length of time needed for the injection procedure was assessed, and subjects were asked to complete a questionnaire regarding their comfort level with each device during the injection procedure as well as immediately after, later that evening, and the next day. RESULTS: Intravitreal injections using the 33-gauge injection device were significantly faster, but there was no significant difference in the incidence or levels of pain between the two needle types. CONCLUSION: The 33-gauge injection device may offer advantages over a standard 30 gauge needle when performing an intravitreal injection. PMID- 24221464 TI - Management of retained subretinal perfluorocarbon liquid. AB - Subretinal perfluorocarbon liquid (PFCL) is a rare but serious complication associated with retinal detachment repair primarily due to the potential for toxic effects of the liquid on various structures of the eye. While it is optimal to detect and remove subretinal PFCL intraoperatively, retained PFCL may be missed in 1% to 11% of cases and not detected until follow-up visits.3,26 In such cases, early intervention appears to be warranted particularly if central vision remains at risk with subfoveally located droplets. Restoration of the foveal contour and attenuation of scotoma size as indicated by optical coherence tomography and microperimetry imaging suggest a good prognosis based on the limited number of case reports reviewed. Prognosis of retained PFCL depends on the location, size, and duration of its contact with retinal structures. PMID- 24221465 TI - Fundus autofluorescence and photoreceptor bleaching in multiple evanescent white dot syndrome. AB - The authors present three cases of multiple evanescent white dot syndrome (MEWDS) with characteristic fundus autofluorescence (FAF) findings, including one patient without any visible white dots on funduscopic examination and another with many more hyperautofluorescent lesions than seen ophthalmoscopically. Additionally, the findings support an alternative mechanism for the hyperautofluorescent lesions in MEWDS, whereby photoreceptor loss causes unmasking of normal underlying retinal pigment epithelium autofluorescence. This hypothesis is demonstrated in two cases by optical coherence tomography showing clear ellipsoid zone attenuation with registration to hyperautofluorescent lesions. It is further supported in two cases by photoreceptor bleaching in successive FAF images captured in the same session leading to diminished autofluorescence intensity of the characteristic dots. PMID- 24221466 TI - Combination anti-VEGF and corticosteroid therapy for idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome. AB - Vision loss associated with the idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome most commonly occurs from macular edema or complications related to neovascularization. The authors present a case of advanced IRVAN associated with a massive exudative response characterized by peripheral retinal telangiectasias, exudative retinal detachment, and macular edema with lipid maculopathy. The patient was managed successfully with visual acuity from hand motion to 20/150 using a combination of local corticosteroids, intravitreal bevacizumab, panretinal photocoagulation, and eventually pars plana vitrectomy for progressive vitreomacular traction. VEGF- and non-VEGF-mediated mechanisms appear to be involved in the pathogenesis of IRVAN given the efficacy of combination therapy. [ophthalmic surg lasers imaging retina. 2013;44:599 602.]. PMID- 24221468 TI - Eight questions with Dr. Puliafito. PMID- 24221467 TI - Small hyperreflective intraretinal material observable on spectral-domain optical coherence tomography in high myopia. AB - With the rapid adoption of spectral-domain optical coherence tomography (SD-OCT) in clinical practice and recent advances in technology, SD-OCT has become an important tool for detecting and managing retinal pathology. The diagnosis of degenerative changes in pathologic myopia can sometimes be difficult and delayed, as the clinical presentation may be subtle. In this series, SD-OCT proved useful in the detection of small hyperreflective intraretinal material in cases in which retinal changes are minimally visible and may explain visual changes that may not have been otherwise elucidated. The results show that SD-OCT in conjunction with clinical examination may provide useful information in the management of patients with pathologic myopia. PMID- 24221469 TI - Carbon-isotope discrimination by leaves of Flaveria species exhibiting different amounts of C3-and C 4-cycle co-function. AB - Carbon-isotope ratios were examined as delta(13)C values in several C3, C4, and C3-C4 Flaveria species, and compared to predicted delta(13)C, values generated from theoretical models. The measured delta(13)C values were within 40/00 of those predicted from the models. The models were used to identify factors that contribute to C3-like delta(13)C values in C3-C4 species that exhibit considerable C4-cycle activity. Two of the factors contributing to C3-like delta(13)C values are high CO2 leakiness from the C4 pathway and pi/pa values that were higher than C4 congeners. A marked break occurred in the relationship between the percentage of atmospheric CO2 assimilated through the C4 cycle and the delta(13)C value. Below 50% C4-cycle assimialtion there was no significant relationship between the variables, but above 50% the delta(13)C values became less negative. These results demonstrate that the level of C4-cycle expression can increase from, 0 to 50% with little integration of carbon transfer from the C4 to the C3 cycle. As expression increaces above 50%, however, increased integration of C3- and C4-cycle co-function occurs. PMID- 24221470 TI - Photoinhibition of photosynthesis in intact kiwifruit (Actinidia deliciosa) leaves: Effect of temperature. AB - Photoinhibition of photosynthesis was induced in attached leaves of kiwifruit grown in natural light not exceeding a photon flux density (PFD) of 300 MUmol.m( 2).s(-1), by exposing them to a PFD of 1500 MUmol.m(-2).s(-1). The temperature was held constant, between 5 and 35 degrees C, during the exposure to high light. The kinetics of photoinhibition were measured by chlorophyll fluorescence at 77K and the photon yield of photosynthetic O2 evolution. Photoinhibition occurred at all temperatures but was greatest at low temperatures. Photoinhibition followed pseudo first-order kinetics, as determined by the variable fluorescence (F v) and photon yield, with the long-term steady-state of photoinhibition strongly dependent on temperature wheareas the observed rate constant was only weakly temperature-dependent. Temperature had little effect on the decrease in the maximum fluorescence (F m) but the increase in the instantaneous fluorescence (F o) was significantly affected by low temperatures in particular. These changes in fluorescence indicate that kiwifruit leaves have some capacity to dissipate excessive excitation energy by increasing the rate constant for non-radiative (thermal) energy dissipation although temperature apparently had little effect on this. Direct photoinhibitory damage to the photosystem II reaction centres was evident by the increases in F o and extreme, irreversible damage occurred at the lower temperatures. This indicates that kiwifruit leaves were most susceptible to photoinhibition at low temperatures because direct damage to the reaction centres was greatest at these temperatures. The results also imply that mechanisms to dissipate excess energy were inadequate to afford any protection from photoinhibition over a wide temperature range in these shade-grown leaves. PMID- 24221471 TI - Photoinhibition of photosynthesis in intact kiwifruit (Actinidia deliciosa) leaves: Recovery and its dependence on temperature. AB - Recovery of photoinhibition in intact leaves of shade-grown kiwifruit was followed at temperatures between 10 degrees and 35 degrees C. Photoinhibition was initially induced by exposing the leaves for 240 min to a photon flux density (PFD) of 1 500 MUmol.m(-2).s(-1) at 20 degrees C. In additional experiments to determine the effect of extent of photoinhibition on recovery, this period of exposure was varied between 90 and 400 min. The kinetics of recovery were followed by chlorophyll fluorescence at 77K. Recovery was rapid at temperatures of 25-35 degrees and slow or negligible below 20 degrees C. The results reinforce those from earlier studies that indicate chilling-sensitive species are particularly susceptible to photoinhibition at low temperatures because of the low rates of recovery. At all temperatures above 15 degrees C, recovery followed pseudo first-order kinetics. The extent of photoinhibition affected the rate constant for recovery which declined in a linear fashion at all temperatures with increased photoinhibition. However, the extent of photoinhibition had little effect on the temperature-dependency of recovery. An analysis of the fluorescence characteristics indicated that a reduction in non-radiative energy dissipation and repair of damaged reaction centres contributed about equally to the apparent recovery though biochemical studies are needed to confirm this. From an interpretation of the kinetics of photoinhibition, we suggest that recovery occurring during photoinhibition is limited by factors different from those that affect post-photoinhibition recovery. PMID- 24221472 TI - Guard cells of Commelina communis L. do not respond metabolically to osmotic stress in isolated epidermis: Implications for stomatal responses to drought and humidity. AB - We investigated the hypothesis that stomatal aperture is regulated by epidermal water status. Detached epidermal peels of Commelina communis L. or leaf disks with epidermis attached were incubated in graded solutions of mannitol (0-1.2 M) containing KCl. In isolated epidermis, guard-cell solute content of open stomata did not decrease in response to desiccation. Guard cells of closed stomata accumulated solutes to the same extent in all levels of mannitol tested. There was no evidence of stress-induced hydroactive closure nor of inhibition of hydroactive opening, even when guard cells of closed stomata were initially plasmolyzed. Hydropassive, osmometer-like, changes in stomatal aperture in the isolated epidermis were induced by addition or removal of mannitol, but these did not involve changes in guard-cell solute content. In leaf disks, stomata exhibited clear hydroactive stomatal responses. Steady-state guard-cell solute content of initially open and initially closed stomata decreased substantially with increasing mannitol. Stomata were completely closed above approx. 0.4 M mannitol, near the turgor-loss point for the bulk leaf tissue. Stomata of Commelina did not exhibit direct hydroactive responses to environmental or epidermal water status. Stomatal responses to water deficit and low humidity may be indirect, mediated by abscisic acid or other signal metabolite(s) from the mesophyll. PMID- 24221473 TI - Phototropic fluence-response curves for Pilobolus crystallinus sporangiophore. AB - Fluence-response relationships were examined for positive and negative phototropism induced by blue (450 nm) and ultraviolet-B (UV-B, 280 nm) light, respectively, in the Pilobolus crystallinus sporangiophore. Fluence-response curves for both blue and UV-B light obtained by changing the fluence by varying exposure time only showed the classical first and second positive bending. However, fluence-response curves obtained by varying the fluence rate were bell shaped irrespective of the length of the exposure time. With increasing exposure time the peak became higher along the ascendant arm and the descendant arm was shifted toward the higher fluence. The Bunsen-Roscoe reciprocity law was valid only when the fluence was less than approx. 400 pmol.m(-2) for both blue and UV-B light. Because the shapes of the fluence-response curves for blue and UV-B light were nearly the same, the photoreceptor systems for both blue and UV-B light are considered to be the same. PMID- 24221474 TI - The apoplastic pool of abscisic acid in cotton leaves in relation to stomatal closure. AB - Suboptimal nitrogen nutrition, leaf aging, and prior exposure to water stress all increased stomatal closure in excised cotton (Gossypium hirsutum L.) leaves supplied abscisic acid (ABA) through the transpiration stream. The effects of water stress and N stress were partially reversed by simultaneous application of kinetin (N(6)-furfurylaminopurine) with the ABA, but the effect of leaf aging was not. These enhanced responses to ABA could have resulted either from altered rates of ABA release from symplast to apoplast, or from some "post-release" effect involving ABA transport to, or detection by, the guard cells. Excised leaves were preloaded with [(14)C]ABA and subjected to overpressures in a pressure chamber to isolate apoplastic solutes in the exudate. Small quantities of (14)C were released into the exudate, with the amount increasing greatly with increasing pressure. Over the range of pressures from 1 to 2.5 MPa, ABA in the exudate contained about 70% of the total (14)C, and a compound co chromatographing with phaseic acid contained over half of the remainder. At a low balancing pressure (1 MPa), release of (14)C into the exudate was increased by N stress, prior water stress, and leaf aging. Kinetin did not affect (14)C release in leaves of any age, N status, or water status. Distribution of ABA between pools can account in part for the effects of water stress, N stress, and leaf age on stomatal behavior, but in the cases of water stress and N stress there are additional kinetinreversible effects, presumably at the guard cells. PMID- 24221475 TI - Mechanisms of fusicoccin action: A dominant role for secondary transport in a higher-plant cell. AB - Fusicoccin (FC) is commonly thought to promote "electrogenic" H(+) extrusion through its action on the H(+)-ATPase of the plant plasma membrane. Nonetheless, essential support from rigorous electrophysiological analysis has remained largely absent. The present investigation surveys the effects of FC on the charge transport properties at the membrane of a higher-plant cell - stomatal guard cells of Vicia faba L. - for which the electrical geometry is defined, and from which the voltage-dependent kinetic characteristic for the pump has been identified. Current-voltage (I-V) relations of the guard cells were determined before and during treatments with FC, and during brief exposures to NaCN plus salicylhydroxamic acid. Responses of the pump and of the ensemble of secondary transport processes were identified in the whole-membrane conductance-voltage relations and in the difference-current-voltage (dI-V) characteristic for the pump. In 0.1 mM K(+), exposure to 10 MUM FC shifted guard-cell potentials negative by 29-61 mV. Current-and conductance-voltage profiles indicated limited changes in the pump I-V characteristic, an observation which was confirmed through explicit kinetic analysis of pump dI-V relations. However, the voltage response was accompanied by a 1.5-to 2.6-fold fall in membrane conductance. These results challenge conventional views of fusicoccin action by ascribing the electrical responses to reduced current passage through secondary transport pathways as well as to enhanced electrogenic ion pumping. PMID- 24221476 TI - Transport of glucose, fructose and sucrose by Streptanthus tortuosus suspension cells : I. Uptake at low sugar concentration. AB - Streptanthus tortuosus Kell. suspension cells will grow in a medium with sucrose as carbohydrate source. It was investigated whether the cells are able to take up sucrose or whether sucrose has to be hydrolyzed to glucose and fructose which eventually are taken up. The detailed quantitative analysis of sugar-uptake rates in the low concentration range up to 1 mM showed the following features: (i) There is definitely no sucrose-uptake system working in the low concentration range; any uptake of radioactivity from labelled sucrose proceeds via hydrolysis of sucrose by cell-wallbound invertase. (ii) Hexoses are taken up by two systems, a glucose-specific system with a K m of 45 MUM and a high V max for glucose and a K m of 6 mM and a low V max for fructose, and a fructosespecific system with a K m of 500 MUM and high a V max for fructose and a K m of 650 MUM and a low V max for glucose. (iii) There is a more than tenfold preference for uptake of the fructose derived from sucrose versus uptake of free fructose, with the result that the kinetic disadvantage of the fructoseuptake system compared to the glucose-uptake system is diminished if sucrose is supplied as the carbon source. It is speculated that invertase might work as an enzyme aiding in fructose transport. PMID- 24221477 TI - Transport of glucose, fructose and sucrose by Streptanthus tortuosus suspension cells : II. Uptake at high sugar concentration. AB - In the concentration range above 1 mM a linear diffusion-like component of sugar uptake by Streptanthus suspension cells is observed. The rate of permeation is the same for sucrose, glucose, fructose and sorbitol, despite the very different uptake features of these sugars at low concentrations, where sorbitol and sucrose are not taken up at all and where different affinities for glucose and fructose are seen. The linear uptake component is responsible for 80% of sugar uptake at 100 mM, and it is an efficient permeation path for sucrose and fructose, which show poor permeation compared to glucose in the low concentration range. The mechanistic nature of the linear uptake component remains obscure: it is not directly dependent on metabolic energy (uncoupler does not inhibit it) and it is neither saturable up to 100 mM nor is it sugar-specific, but it is changeable, for instance, by plasmolysis or by protoplast generation. The permeation rates are very similar to those found in other plants for the linear component, but are much higher than in artificial membranes. These features are neither fully compatible with diffusion through a lipid phase nor with catalysed transport, and it is therefore suggested that this linear uptake proceeds through hydrophilic domains of the membrane. The linear uptake component will have consequences for apoplastic sugar concentration, sugar-accumulation factors and cell metabolism. PMID- 24221478 TI - Coarse control of sucrose-phosphate synthase in leaves: Alterations of the kinetic properties in response to the rate of photosynthesis and the accumulation of sucrose. AB - It has been investigated whether diurnal rhythms of sucrose-phosphate synthase (SPS) are involved in controlling the rate of photosynthetic sucrose synthesis. Extracts were prepared from spinach (Spinacia oleracea L.) and barley (Hordeum vulgare L.) leaves and assayed for enzyme activity. The activity of SPS increased in parallel with a rising rate of photosynthesis, and was increased by feeding mannose and decreased by supplying inorganic phosphate. In leaf material where sucrose had accumulated during the photoperiod or when sucrose was supplied exogenously, SPS activity decreased. During a diurnal rhythm, SPS activity increased after illumination, declined gradually during the light period, decreased further after darkening and then recovered gradually during the night. These changes did not involve an alteration of the maximal activity, but were caused by changes in the kinetic properties, revealed as a change in sensitivity to inhibition by inorganic phosphate. In experiments which modelled the response of SPS to changing metabolite concentrations, it was shown that these alterations of kinetic properties would strongly modify the activity of SPS in vivo. It is proposed that SPS can exist in kinetically distinct forms in vivo, and that the distribution between these forms can be rapidly altered. As the rate of photosynthesis increases there is an activation of SPS, which may be directly or indirectly linked to changes in the availability of Pi. This activation can be modified by factors related to the accumulation of sucrose. Under normal conditions there is a balance between these factors, and the leaf contains a mixture of the different forms of SPS. PMID- 24221479 TI - The effect of auxin concentration on cytokinin stability and metabolism. AB - The stability of [(3)H]zeatin riboside supplied to freshly excised tobacco pith explants was found to be inversely related to alpha-naphthaleneacetic acid concentration in the incubation medium. At higher concentrations of alpha naphthaleneacetic acid greater breakdown of [(3)H]zeatin riboside was indicated by higher levels of degradative metabolites (adenine, adenosine and adenosine nucleotides) formed. This auxin effect on cytokinin metabolism appears to be mediated, at least in part, through cytokinin oxidase. The results of in-vitro assays carried out with partially purified enzyme from corn kernels substantiale this conclusion. These findings are discussed in relation to recent observations of auxin and cytokinin levels in crown-gall tumours with altered morphology. PMID- 24221480 TI - Preferential synthesis of plastid DNA and increased replication of plastids in cultured tobacco cells following medium renewal. AB - During the culture of tobacco BY 2 cells derived from Nicotiana tabacum L. cv. Bright Yellow 2, morphological changes of plastid (pt) nucleoids and their replication were examined by fluorescence microscopy after staining with 4'6 diamidino-2-phenylindole. Upon transfer to fresh medium, the fluorescence intensity originating from pt nucleoids increased markedly. Copy numbers of ptDNA per cell calculated from the quantitative data by super-sensitive microspectroscopy increased 11-fold within 1 d of culture to reach 11 000, then decreased gradually to 1 000 after one week of culture. Autoradiography by labelling with [(3)H]thymidine showed that DNA synthesis in plastids occurred exclusively during the first day of culture, whereas nuclear DNA synthesis was observed from the first to the sixth day of culture. Replication of plastids was most frequently observed on the second day. Thereafter the formation of starch granules predominated in plastids up to the fifth day of culture, but the starch granules disappeared in the stationary-phase cells. The meaning of such preferential synthesis of ptDNA upon transfer to fresh medium is discussed in relation to the interaction between plastids and nuclei. PMID- 24221481 TI - Rhythms of fragrance emission in flowers. AB - A method for the sampling of volatiles emitted by individual flowers is described. Sampling over periods of 3 h allowed the examination of diurnal changes in quantity and quality of fragrance. In the species studied, Odontoglossum constrictum Lindl., Citrus medica L., Hoya carnosa R. Br., and Stephanotis floribunda Brongs., the fragrance was characterized by a few major components accompanied by a larger number of minor components. Flowers of all species produced volatiles in a rhythmical, diurnal fashion. Whereas in detached flowers of O. constrictum and C. medica rhythmicity could be observed for up to four cycles, flowers of H. carnosa showed this phenomenon only when attached to the plant. Maxima of emission were observed during the day in C. medica and O. constrictum whereas in H. carnosa it occurred during the night. In S. floribunda a conspicuous asynchronism of the emission of different volatiles was observed, resulting in the rhythmical change of fragrance quality. PMID- 24221482 TI - Circadian rhythmicity of fragrance emission in flowers of Hoya carnosa R. Br. AB - In flowers of Hoya carnosa R. Br. the nocturnal emission of fragrance occurs according to an endogenous circadian rhythmicity. This was demonstrated by the continuation of rhythmical emission for two to three cycles under conditions of permanent illumination. The free-running period was approx. 29 h under these conditions. The inversion of light/dark cycles caused the entrainment of the next peak of emission by approx. 12 h whether the inversion was started with a light period or a with dark period prolonged for 12 h. When only the flower used for fragrance analysis was subjected to an inverted photoperiod, the rest of the plant remaining under the original light/dark cycle, the synchronization of fragrance emission occurred according to the Zeitgeber perceived by the individual flower. PMID- 24221483 TI - The relationship between contents of photosynthetic metabolites and the rate of photosynthetic carbon assimilation in leaves of Amaranthus edulis L. AB - The relationship between the gas-exchange characteristics of attached leaves of Amaranthus edulis L. and the contents of photosynthetic intermediates was examined in response to changing irradiance and intercellular partial pressure of CO2. After determination of the rate of CO2 assimilation at known intercellular CO2 pressure and irradiance, the leaf was freeze-clamped and the contents of ribulose-1,5-bisphosphate, glycerate-3-phosphate, fructose-1,6-bisphosphate, glucose-6-phosphate, fructose-6-phosphate, triose phosphates, phosphoenolpyruvate, pyruvate, oxaloacetate, aspartate, alanine, malate and glutamate were measured. A comparison between the sizes of metabolite pools and theoretical calculations of metabolite gradients required for transport between the mesophyll and the bundle-sheath cells showed that aspartate, alanine, glycerate-3-phosphate and triose phosphates were present in sufficient quantities to support transport by diffusion, whereas pyruvate and oxaloacetate were not likely to contribute appreciably to the flux of carbon between the two cell types. The amounts of ribulose-1,5-bisphosphate were high at low intercellular partial pressures of CO2, and fell rapidly as the CO2-assimilation rate increased with increasing intercellular partial pressures of CO2, indicating that bundle sheath CO2 concentrations fell at low intercellular partial pressures of CO2. In contrast, the amount of phosphoenolpyruvate and of C4-cycle intermediates declined at low intercellular partial pressures of CO2. This behaviour is discussed in relation to the co-ordination of carbon assimilation between the Calvin and C4 cycles. PMID- 24221484 TI - Particle density and protein composition of the peribacteroid membrane from soybean root nodules is affected by mutation in the microsymbiont Bradyrhizobium japonicum. AB - Particle frequency of the peribacteroid membrane (PBM) from nodules of Glycine max (L.) Merr. cv. Maple Arrow infected with Bradyrhizobium japonicum 61-A-101 (wild-type strain) was determined by freeze-fracturing to be about 2200.MUm(-2) in the protoplasmic fracture face and 700.MUm(-2) in the exoplasmic fracture face. In membranes isolated from nodules infected with the mutant RH 31-Marburg of B. japonicum, the particle frequency was similar in both fracture faces with 1200-1300 particles.MUm(-2). Analysis of particlesize distribution on peribacteroid membranes showed a loss, especially of particle sizes larger than 11 nm, in the mutant-infected nodules. Two-dimensional gel electrophoresis (isoelectric focussing and sodium dodecyl sulfate-polyacrylamide) showed 27 different polypeptides in the PBM from nodules infected with the wild-type strain, four of which were absent from the PBM of nodules infected with the mutant RH 31-Marburg, which also exhibited one extra small-molecular-weight polypeptide. At least 14 of the 27 polypeptides in the PBM from the wild-type infected nodule were glycoproteins. In three of these glycoproteins, post translational modifications were either lacking or different when the membrane was derived from mutant-infected nodules. PMID- 24221485 TI - Transport and posttranslational processing of the vacuolar enzyme alpha mannosidase in jack-bean cotyledons. AB - alpha-Mannosidase (EC 3.2.1.24) is a vacuolar enzyme which occurs abundantly in the cotyledons of the jack-bean (Canavalia ensiformis (L.) DC). The mature enzyme is a tetramer with two polypeptides each of relative molecular mass (Mr) 66000 and Mr 44000. The enzyme has an interesting molecular structure because in its native form, it does not bind to concanavalin A (ConA) in spite of the presence of a high-mannose glycan. alpha-Mannosidase is synthesized in the developing cotyledons of jack-beans at the same time as the abundant proteins canavalin and ConA. The enzyme is synthesized as a precursor which has an Mr of 110000 and is associated with the endoplasmic reticulum (ER). Antibodies against the deglycosylated subunits cross-react with the Mr-110000 precursor. Processing of the precursor to the constituent polypeptides occurs posttranslationally, probably in the protein bodies. Immunocytochemical evidence shows that alpha mannosidase is present in the ER and the Golgi complex of developing cells, and accumulates in the protein bodies.Labeling with [(3)H]glucosamine shows that after processing only the Mr-66000 polypeptide has glucosamine-containing glycans. The synthesis of these glycans is inhibited by tunicamycin, indicating that they are asparagine-linked oligosaccharides. Analysis of the glycans shows that there is a large glycan that is retained by ConA and a small glycan that is not retained by ConA. The large glycan is only partially sensitive to alpha mannosidase because of the presence of a terminal glucose residue. Cross-reaction of the large subunit with an antiserum directed against small, complex glycans of plant glycoproteins indicates that this polypeptide probably has a xylose containing glycan. Pulse-chase experiments carried out in the presence of tunicamycin show that the presence of glycans is not required for transport of alpha-mannosidase out of the ER-Golgi system. PMID- 24221486 TI - The activity of powdery-mildew haustoria after feeding the host cells with different sugars, as measured with a potentiometric cyanine dye. AB - The biotrophic parasite Erysiphe graminis f. sp. hordei produces haustoria within the cells of its host Hordeum vulgare. To determine the physiological activity of these haustoria, the electric potential across the membranes in the mitochondria of the haustorium was studied. The membrane potential was estimated with the fluorescent potentiometric cyanine dye 3,3'-dibutyloxacarbocyanine iodide. The addition of depolarizing agents (carbonylcyanide m-chlorophenylhydrazone, 2,4 dinitrophenol or KCN) to infected cells resulted in an increase of fluorescence after the addition of low concentrations or a decrease of fluorescence after the addition of higher concentrations. When the infected host cell was fed with increasing concentrations of D-glucose (25, 50, 75 mM), corresponding decreases of fluorescence were measured immediately in the mitochondria of the fungal haustoria. Sucrose induced a similar reduction of fluorescence about 20 min late. D-Galactose and D-fructose induced a somewhat smaller reduction of fluorescence, L-glucose and D-glucitol had no effect. The results indicate that haustoria take up glucose from the host cells immediately. Sucrose, D-galactose and D-fructose seem to require time to be metabolized before their products reach the fungal haustorium or mitochondria. PMID- 24221487 TI - Abiotic factors elicit sesquiterpenoid phytoalexin production but not alkaloid production in transformed root cultures of Datura stramonium. AB - The treatment of root cultures of Datura stramonium with copper and cadmium salts at external concentrations of approximately 1mM has been found to induce the rapid accumulation of high levels of sesquiterpenoid defensive compounds, notably lubimin and 3-hydroxylubimin. These compounds were undetectable in unelicited cultures. No net change was seen in the alkaloid content of the system following treatment with Cu(2+) or Cd(2+), the tropane alkaloid titre apparently being insensitive to elicitation. However, a considerable rapid and, in some instances, reversible release of alkaloid was observed. This resulted in the appearance of up to 50-75% of the total alkaloid in the medium after 40-60 h. Subsequently, in cultures treated with Cu(2+) ions, though not in cultures treated with Cd(2+) ions, this alkaloid was re-absorbed. These observations show how, in a single system, different groups of secondary products can show distinct differences in their responses to potential elicitors. PMID- 24221488 TI - Avoidance of precipitation and carbohydrate breakdown in autoclaved plant tissue culture media. AB - The extent of breakdown of fructose and glucose derived from sucrose in the medium of Murashige and Skoog (1962) during autoclaving was investigated by polarographic measurement. Although not present in the original MS medium but often used in place of FeSO4 + Na2-EDTA, FeNa-EDTA was found to be primarily responsible for catalyzing the breakdown of these monosaccharides. It would therefore be good practice to autoclave FeNa-EDTA separate from the carbohydrate constituents of the medium in order to reduce the formation of toxic substances derived from the latter's breakdown. Autoclaving FeNa-EDTA separately has the additional advantage of preventing precipitation of certain micronutrient elements. Further precipitation can be avoided by autoclaving FeNa-EDTA and KH2PO4 together, but separately, from other components of the medium. By eliminating precipitation and minimizing the breakdown of monosaccharides during autoclaving, it is possible to improve the quality of the medium without resorting to sterilization by filtering. PMID- 24221489 TI - Histology of, and physical factors affecting, transient GUS expression in pearl millet (Pennisetum glaucum (L.) R. Br.) embryos following microprojectile bombardment. AB - Transient GUS (beta-glucuronidase) expression was visualized in whole and sectioned embryos of Pennisetum glaucum (L.) R. Br. (pearl millet) after microprojectile bombardment with pMON 8678 DNA. Strongest GUS expression occurred in cells located in the center of GUS positive spots with decreasing intensity in surrounding cells. GUS positive cells could be seen up to 12 cell layers beneath the epidermis. Needle-like crystals of the GUS assay product were found throughout the cytoplasm of GUS positive cells. The number of GUS positive spots was correlated to the microprojectile spread pattern on the medium surface. Shorter bombardment distances (6.6 and 9.8 cm) and the standard accelerator speed gave the best results for transient expression but also caused maximum tissue damage. The speed and distance, however, had little influence on the ability of bombarded embryos to form compact callus. The developmental stage of the bombarded immature embryos was the determining factor in the formation of compact callus, from which plants were regenerated. PMID- 24221490 TI - Regulation of DNA synthesis and cell division by polyamines in Catharanthus roseus suspension cultures. AB - Various inhibitors of polyamine biosynthesis were used to study the role of polyamines in DNA synthesis and cell division in suspension cultures of Catharanthus roseus (L.) G. Don. Arginine decarboxylase (ADC; EC 4.1.1.19) was the major enzyme responsible for putrescine production. DL alpha difluoromethylarginine inhibited ADC activity, cellular putrescine content, DNA synthesis, and cell division. The effect was reversible by exogenous putrescine. Ornithine decarboxylase (ODC; EC 4.1.1.17) activity was always less than 10% of the ADC activity. Addition of DL alpha-difluoromethylornithine had no effect on ODC activity, cellular polyamine levels, DNA synthesis, and cell division within the first 24 h but by 48 to 72 h it did inhibit these activities. Methylglyoxal bis(guanyl-hydrazone) inhibited S-adenosylmethionine decarboxylase (EC 4.1.1.50) activity without affecting DNA synthesis and cell division. PMID- 24221491 TI - Clonal propagation of Virginia Pine (Pinus virginiana Mill.) by organogenesis. AB - Clonal propagation of Virginia Pine (Pinus virginiana Mill.) was achieved by organogenesis on cotyledon explants. The influence of several cytokinins and abscisic acid on adventitious shoot production from cotyledon explants was investigated. Benzyladenine was more effective in shoot induction than three other cytokinins tested. Benzyladenine (22.2 MUM) in combination with naphthaleneacetic acid(0.05 MUM) in a Gresshoff and Doy (1972) medium was found to increase shoot bud production. Abscisic acid (7.6 MUM) in combination with benzyladenine and naphthaleneacetic acid enhanced shoot formation by an additional 65%. Root initiation was achieved with 0.5 strength Gresshoff and Doy media amended with naphthaleneacetic acid (1.3 MUM), indole-3-butyric acid (1.2 MUM) and benzyladenine (0.4 MUM). Over 2400 plantlets from 2 families survived and were transferred to a greenhouse in preparation for field planting. After ten months, the maximum number of surviving plantlets/seed explant from these two sources was 57 for family ALPV-38 and 41 for family ALPV-78, respectively. PMID- 24221492 TI - Transformation by Agrobacterium rhizogenes and regeneration of transgenic shoots of the wild soybean Glycine argyrea. AB - Glycine argyrea accession G1420 was evaluated for its response to inoculation with Agrobacterium rhizogenes strains LBA9402 and A4T, carrying wild type Ri plasmids, and by strains R1601 and A4TIII with engineered plasmids. Hypocotyls from young seedlings were the most responsive in producing roots at inoculation sites. Root production was also dependent on bacterial concentration. Excised, cultured roots produced green nodular callus which regenerated shoots on SC2 medium containing 1.1 mg l(-1) 6-benzylaminopurine and 0.005 mg l(-1) indole-3 butyric acid. The transformed nature of the roots and of callus regenerating shoots was confirmed by the presence of opines and by dot blot analysis for Ri TL DNA. Tissues regenerated from roots transformed by A. rhizogenes strains R1601 and A4TIII exhibited NPTII enzyme activity, confirming the stable integration and expression of the chimaeric kanamycin resistance gene in transgenic tissues. PMID- 24221493 TI - Relationship between protoplast size and critical field strength in protoplast electropulsing and application to reliable DNA uptake in Brassica. AB - Protoplast diameter, a physical parameter controlling the susceptibility to electropermeation, was observed to vary between different batches of Brassica napus and Brassica campestris protoplasts. In order to control the permeation field strength associated with the protoplast size, we investigated the mathematical relationship between permeant field strength and protoplast size by measuring electroloading of the calcein dye under conditions that did not alter protoplast survival. A roughly linear relationship was obtained when the permeant field strength was plotted against the reciprocal of the radius. The plot characteristics were found to be tissue specific (mesophyll, hypocotyl and cotyledon), species specific (turnip, rapeseed) and modulated by the pulse duration. These plots were used as reference curves to determine accurate electrical conditions for DNA transfer whatever the size distributions of different protoplast batches. PMID- 24221494 TI - Cryopreservation of immature embryos of Theobroma cacao. AB - Immature, white zygotic embryos of Theobroma cacao L. (cacao) retained the ability to produce callus and to undergo somatic embryogenesis after slow hydrated freezing and desiccated fast freezing in liquid nitrogen. The highest rate of somatic embryogenesis occurred in embryos which were precultured on a medium containing 3% sucrose, frozen slowly with cryoprotectants before exposure to liquid nitrogen, and recovered on a medium containing 3 mg/liter NAA. Embryos precultured on media containing sucrose increasing to 21% had a higher rate of survival but were less embryogenic after freezing. These results suggest that immature embryos might be used for long-term germplasm storage of T. cacao germplasm. PMID- 24221495 TI - A segment of rye chromosome 1 enhances growth and embryogenesis of calli derived from immature embryos of wheat. AB - The influence of the short arm of rye chromosome 1 (1RS) from Secale cereale var. Imperial on the growth and differentiation of callus cultures from wheat Triticum aestivum var. Chinese Spring immature embryos was analysed. This chromosome arm was found to stimulate both embryogenesis and the rate of growth of calli. Recombinant lines carrying segments of 1RS were used to delineate the regions of 1RS responsible for the tissue culture effects. The enhancement of embryogenesis and the stimulation of growth were shown to be associated with two distinct genetic regions of the chromosome arm; the former is located between the centromere and the Sec 1 locus, while the latter is situated in the immediate vicinity of the Sec 1 locus. PMID- 24221496 TI - Biochemical differences between carrot inbreds differing in plant regeneration potential. AB - Cultures derived from domestic carrot (Daucus carota L.) inbreds were found to vary with respect to regeneration potential as measured by the production of somatic embryos in suspension cultures. A number of biochemical parameters previously reported to distinguish embryogenic from non-embryogenic cultures of other species were measured in these carrot cell lines. Ethylene production was found to be inversely related to regeneration potential. The cell line producing the greatest number of somatic embryos exhibited the lowest rate of ethylene biosynthesis, even when grown on 2, 4-D-containing maintenance medium. A specific isozyme of acid phosphatase was associated with embryogenic calli. Proteins visualized by SDS-PAGE did not discriminate between embryo-forming and proliferating calli in all inbreds. PMID- 24221497 TI - A liquid cytokinin pulse induces adventitious shoot formation from Douglas-fir cotyledons. AB - The effects of high-concentration, 2-h liquid pulses of N(6)-benzylaminopurine (BA) and thidiazuron (TD) on adventitious bud and shoot formation were tested in cotyledons of Douglas-fir (Pseudotsuga menziesii). Seedling age proved important; on average, cotyledons from the youngest seedlings formed 10-fold more buds than cotyledons from the oldest seedlings. Optimal cytokinin concentrations for the youngest cotyledons were 400 and 800 MUM BA, and 100 and 200 MUM TD. Shoots developed best from buds induced with 300, 400, and 800 MUM BA. Four gelling agents were tested; BRL agarose yielded more than three times the number of buds, and Gelrite nearly twice the number of buds, as either Sigma agar or Difco Bacto Agar. One of the best treatments (400 MUM BA, agarose) yielded more cotyledons with buds, and more buds per cotyledon, than when cytokinins were incorporated into the growth medium. PMID- 24221498 TI - The detection and characterization of bacteria-sized protists in "Protist-free" filtrates and their potential impact on experimental marine ecology. AB - Nuclepore filters of 0.6-1.0MUm pore size have been used to prepare "protist free" water for a number of studies in microbial ecology. This procedure has been called into question by a recent study claiming that a significant portion of bacterial loss in filtrates could be due to uncharacterized predators passing through 0.6MUm filters. We were unable to directly observe protists in 0.6MUm filtrates using phase contrast, epifluorescence, or transmission electron microscopy. Using the culture techniques of rice grain enrichment and most probable number, however, we were able to observe and quantify several species of bacterivorous nanoflagellates that developed not only in 0.6MUm, but also in 0.4MUm seawater filtrates. The ability of predacious nanoflagellates to squeeze through bacteria-sized pores questions studies of bacterial production and chemical cycling that have assumed protist-free filtrates. PMID- 24221499 TI - Adsorption mediated decrease in the biodegradation rate of organic compounds. AB - A negative correlation between adsorption of low molecular weight organic acids and sugars onto a hydroxyapatite surface and biodegradation rates of the compounds in the presence of the mineral was observed. Qualitatively, the effect was the same whether the organics were equilibrated with the surface prior to the addition of organisms or the organisms were preattached to the surface. Glucose, acetic acid, succinic acid, glutamic acid, and citric acid showed equilibrium adsorption values ranging from 0-94% from a 2MUM solution. Changes in both respiration and assimilation of the substrates in the presence of hydroxyapatite were inversely correlated with adsorption. PMID- 24221500 TI - Effects of organic amendments on sulfate reduction activity, H2 consumption, and H 2 production in salt marsh sediments. AB - Sulfate reduction activity (SRA) was measured via the radioactive tracer ((35)SO4 (=)) technique in sediment samples from the Canary Creek Marsh in Lewes, Delaware. Basal levels of SRA ranged from 130 to 319 nmoles of sulfate reduced/gram dry sediment/hour. With the exception of lactate and formate, all organic acids tested resulted in no stimulation of SRA, whereas straight chain alcohols (C1-C4) all gave a significant increase in SRA. In addition, H2, glucose, and cellobiose caused a twofold or greater increase in SRA, while cellulose amendments did not alter SRA. Molybdate, an inhibitor of sulfate reducing bacteria (SRB), caused a total inhibition in SRA. 2-Bromoethanesulfonic acid (BES), an inhibitor of methanogenic bacteria, caused a slight decrease in SRA. Hydrogen was not produced in detectable quantities in unamended samples but was produced in large amounts in glucose-amended samples. Hydrogen was rapidly consumed in unamended samples with molybdate additions causing a significant decrease in the rate of H2 consumption. A variety of organic amendments was found to stimulate H2 uptake. These studies suggest that SRB are stimulated by a large variety of organic amendments in situ and that SRB play a major role in maintaining low partial pressures of H2 in marsh sediments. PMID- 24221501 TI - Metabolism of low molecular weight organic compounds by sulfate-reducing bacteria in a Delaware salt marsh. AB - Oxidation of acetate, lactate, pyruvate, and ethanol to CO2 in anaerobic salt marsh sediments was rapid, with the oxidation rate being significantly inhibited (60-90% decrease) in the presence of 2 mM sodium molybdate, an inhibitor of sulfate-reducing bacteria (SRB). 2-Bromoethanesulfonic acid (BES), an inhibitor of methanogenic bacteria, generally had no effect on the oxidation rate. Acetate was the only intermediate product detected in the oxidation of lactate and ethanol. Competition studies with lactate, acetate, and ethanol indicated that the preferred order of substrate utilization was lactate, then acetate, then ethanol. The turnover times of these three compounds in salt marsh sediments via the combined CO2 plus acetate pool was rapid (10-13 hours) with a two- to threefold increase in the turnover time in the presence of molybdate. These results strongly suggest that SRB play a major role in the terminal metabolism of low molecular weight organic compounds in anaerobic salt marsh sediment. PMID- 24221502 TI - Microbial response to crude oil and Corexit 9527: SEAFLUXES enclosure study. AB - The response of marine bacteria to Corexit 9527, with and without Prudhoe Bay crude oil labeled withn-(1-(14)C)hexadecane, in a temperate pelagic environment was monitored over 22 days using controlled ecosystem enclosures. The results indicated that Corexit and Corexit-dispersed crude oil stimulated bacterial production by serving as substrates and/or by inducing the release of organic compounds from the indigenous phytoplankton population. Highest bacterial standing stock was observed in the enclosure treated with a mixture of Corexit and crude oil, in which a large fraction of the predominant bacterivores were eliminated. Biodegradation appeared to be more significant than abiotic processes in contributing to the loss of low volatility n-alkanes in Corexit-dispersed oil. Twenty-two days following its addition, 50% of the radiotracer was recovered: 3% in the suspended particulate fraction, 10% in sedimentary material, 36% as CO2, and less than 1% in the dissolved organic pool. PMID- 24221503 TI - Development of a heterotrophic bacterial community within a closed prawn aquaculture system. AB - The quantitative and qualitative development of a heterotrophic bacterial community in seawater was studied throughout an experimental rearing of the prawnPenaeus japonicus. The maturation of juvenile prawns had been carried out for 8 months in aerated tanks of seawater without any water renewal. Bacteria (337 strains) were isolated from seawater, which had been sampled at different times. Samples from one of the mussels used to feed the prawns and from the digestive tract of one prawn each supplied 40 more strains. 101 tests were performed on each strain, and cluster analysis showed the existence of 4 different groups containing 95% of the sampled strains. Characteristics of the various samples and groups were described in terms of ecotype diversities, catabolic potentialities, nutritional capacities, and morpho-physiological groups. Until nitrification attained a steady state, the heterotrophic community clearly decreased in number and was composed mostly of auxotrophic bacteria (pseudomonads andMoraxella-Acinetobacter groups). These bacteria needed growth factors and were unable to use amino acids (group B). At the end of the experiment (7 months) the bacteria isolated from the water were vibrios and enterobacteria, as were those isolated from the prawn and the mussel. They clustered together in group A. The number of strains that clustered with those of natural seawater (group E) decreased steadily during the experimental period. PMID- 24221504 TI - Attenuated osteoarticular phenotype of type VI mucopolysaccharidosis: a report of four patients and a review of the literature. AB - Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI, OMIM 253200) is caused by mutations in the gene coding for N-acetylgalactosamine-4-sulfatase (4 sulfatase, arylsulfatase B, ARSB, EC 3.1.6.12), a lysosomal enzyme involved in the degradation of dermatan sulfate (DS). The clinical presentation of MPS VI varies greatly with respect to age of onset and rate of disease progression. This report focuses on the attenuated form of MPS VI, which can go unrecognized for years and often presents with atypical signs or symptoms. We described a cohort of MPS VI patients (n = 4) heterozygous for the p.Y210C mutation who had a significant osteoarticular involvement at the onset of their disease and who were diagnosed years or even decades later. We have also reviewed the literature (n = 36). Two types of attenuated MPS VI phenotypes could be distinguished: osteoarticular and cardiac. The majority of MPS VI patients reported so far as relatively attenuated presented with an essentially osteoarticular phenotype associated with the p.Y210C mutation. Patients homozygous for the p.R152W mutation presented with a cardiac phenotype, which, despite fulfilling the generally used criteria for attenuated phenotype, may lead to fast disease progression and abrupt death. The knowledge of natural history and genotype phenotype correlation may help in developing a tailored therapy potentially using enzyme replacement therapy with substrate reduction therapy or chaperones. PMID- 24221505 TI - Translation into Brazilian Portuguese, cross-cultural adaptation and validation of the Stanford presenteeism scale-6 and work instability scale for ankylosing spondylitis. AB - Loss of productivity at work, as a result of health problems, is becoming an issue of interest due to the high burden it represents in society. The measurement of such phenomenon can be made using generic and specific scales for certain diseases such as the Stanford Presenteeism Scale (SPS-6) and the Work Instability Scale for Ankylosing Spondylitis (AS-WIS), specific for patients with ankylosing spondylitis (AS). The aim of this study was to translate and perform a cross-cultural adaptation of SPS-6 and AS-WIS into Portuguese and check their psychometric properties. The study also aimed to evaluate the relationship between the general scores of the scales and the main sociodemographic and clinical data, lifestyles, and absenteeism in patients with AS and correlate these variables with SPS-6 and AS-WIS scales. A sample of 120 patients with AS and 80 workers at a university hospital was evaluated. The processes for the translation and cross-cultural adaptation of the instruments followed preestablished steps and rules presented in the literature. For the evaluation of measurement properties and correlations between scales, intra-class correlation coefficient (reproducibility analysis), Cronbach alpha (internal consistency), and Pearson correlation coefficient (validity) were employed. The inter-observer (0.986) and intra-observer (0.992) reproducibilities of the AS-WIS were shown to be high as well as the internal consistency (0.995). Similarly, the inter observer reliability of SPS-6 was considered good (0.890), although it showed a poorer performance when considering the same observer (Pearson correlation coefficient = 0.675 and intra-class correlation = 0.656). Internal consistency, for the total number of items, as measured by Cronbach alpha, was 0.889. The validity of the scales was evaluated thru the comparison of the achieved scores with the results of the WLQ, SF-36, ASQoL, BASFI, BASDAI, HAQ-S, and SRQ-20 instruments. Correlations between loss of productivity at work, worse quality of life, presence of emotional disturbances, and worse health conditions were positive. The process of translation, cross-cultural adaptation, and validation of the SPS-6 as a generic measurement for the loss of productivity at work and of the AS-WIS as a specific measurement for patients with AS are valid, reproducible, and specific instruments to be used in Brazil. In both scales, productivity at work was associated to advanced age, higher rate of absenteeism in the last month and year, presence of peripheral arthritis, and a larger number of comorbidities in patients with AS. The AS-WIS and SPS-6 showed a good correlation among them although they are not mutually exclusive but supplementary. PMID- 24221506 TI - Does vitamin D affect femoral cartilage thickness? An ultrasonographic study. AB - This study aims to investigate the association between vitamin D levels and distal femoral cartilage thickness in healthy subjects. Eighty patients who were admitted to our outpatient clinic between May and July 2013 were classified into three subgroups according to their 25-OH vitamin D levels of <10, 10-20, and >=20 ng/mL. Distal femoral cartilage thickness was measured from the midpoints of the right medial condyle (RMC), right lateral condyle (RLC), right intercondylar area (RIA), left medial condyle (LMC), left lateral condyle (LLC), and left intercondylar area (LIA) by using musculoskeletal ultrasound (US). The group with severe vitamin D deficiency (<10 ng/mL) had thinner femoral cartilage thickness at LMC (p = 0.005). Positive correlations were determined only between vitamin D levels and US measurements in the severe vitamin D deficiency group at RLC (r = 444, p = 0.020), LMC (r = 357, p = 0.067), and LLC (r = 568, p = 0.002). Low levels of vitamin D seem to affect the femoral cartilage thickness, adversely. Further studies are necessary to ascertain the clinical relevance of this change in cartilage thickness and whether vitamin D supplementation can reverse the cartilage thinning process or the allied clinical symptoms in the course of knee osteoarthritis. PMID- 24221507 TI - Auditory event-related signals in mouse ERG recordings. AB - PURPOSE: In murine disease models, particularly in cases when retinal electrical activity is reduced, an event-related component becomes apparent that does not change with the stimulus intensity in electroretinogram (ERG) recordings. In this work, we show that this electric component is evoked by the sound of the flash discharge rather than the light flash itself. METHODS: Wild-type mice (C57BL/6), mice with rod function only (Cnga3 (-/-)), mice lacking any photoreceptor function (Cnga3 (-/-) rho (-/-)), and mice with no auditory function (Cdh23 (vAlb/vAlb) ) were examined with Xenon flash ERG systems. An acoustic noise generator was used to mask discharge sounds. RESULTS: ERG recording modalities were identified where usually no discernible response can be elicited. These include photopic conditions in Cnga3 (-/-) mice, photopic conditions together with very low stimulus intensities in C57BL/6 mice, and both scotopic and photopic conditions in Cnga3 (-/-) rho (-/-) mice. However, in all of these cases, small signals, featuring an initial a-wave like deflection at about 20 ms and a subsequent b-wave like deflection peaking at about 40 ms after the flash, were detected. In contrast, such signals could not be detected in deaf Cdh23 (vAlb/vAlb) mice. Furthermore, masking the Xenon discharge sound by continuous acoustic noise led to a loss of the event-related signals in a reversible manner. CONCLUSIONS: We could identify an auditory event-related component, presumably resembling auditory evoked potentials, as a major source of ERG signals of non visual origin in mice. This finding may be of particular importance for the analysis and interpretation of ERG data in mice with reduced visual responses. PMID- 24221508 TI - Recovery of plastids from photooxidative damage: Significance of a plastidic factor. AB - It was inferred from previous findings that a plastid-derived factor (plastidic factor) is involved in the transcriptional control of nuclear genes coding for proteins destined for the chloroplast. Photooxidative damage to the plastid destroys the ability of the organelle to give off this factor. Cytosolic enzyme levels are not impaired if plastids are damaged, and morphogenesis of seedlings is normal. The only exception found so far is nitrate reductase, a cytosolic enzyme, which is regulated by the cellas if it were a plastidic protein. In the present study we have shown that the plastids in the mesophyll of mustard (Sinapis alba L.) cotyledons, damaged by 3 h photooxidation in red light (6.8 W.m(-2)) and then returned to darkness or to continuous, non-photooxidative far red light (cFR), recover from photooxidative damage. The rate of recovery is stimulated by phytochrome (operationally, cFR). Since the cytosolic enzyme nitrate reductase is affected by the different treatments in principally the same way as the levels of plastidic enzymes, we conclude that it is recovery of the plastids' ability to give off the plastidic factor rather than structural recovery which leads to recovery of gene expression and protein (and chlorophyll) re-accumulation. The extent of recovery varied according to the enzyme and this variation could be explained by different plastidic-factor requirements for gene expression. This explanation was confirmed by measurements of translatable mRNAs. It was found that LHCP-gene expression (light-harvesting chlorophyll a/b-binding protein of photosystem II) is far more sensitive to photooxidative damage of the plastids than SSU-gene expression (small subunit of ribulose-1.5-bisphosphate carboxylase). Correspondingly, recovery is expressed to a much greater extent in the latter than in the former case. PMID- 24221509 TI - The detection of fucose residues in plant nuclear envelopes. AB - Protoplasts from suspension-culturedDaucus carota L. cells, when fixed and incubated with fluorescein conjugates of the fucosyl-specific lectinUlex europaeus agglutinin I, exhibited the following pattern of labeling: plasma membranes were not marked, but striking halos of fluorescence appeared around the periphery of all nucleic. Identical observations were made with protoplasts fromVicia faba L. leaves,Pisum sativum L. epicotyls,Zea mays L. roots andGlycine max L. cell suspensions, as well as with nucleic in cell-free preparations from the same sources. These results indicate that in a broad spectrum of angiosperm cells, fucose residues are associated with the nuclear envelope. The relationship of this finding in plant cells to recent discoveries regarding nuclear glycoconjugates in animal cells remains to be explored. PMID- 24221510 TI - The sensitive period for light and temperature regulation of sporangiophore development inPhycomyces. AB - Light and temperature markedly influence sporangiophore development inPhycomyces blakesleeanus. Under normal conditions in the dark, low temperature drastically stimulates the production of dwarf sporangiophores (microphorogenesis) and inhibits that of giant sporangiophores (macrophorogenesis). These effects of low temperature could still be observed if applied only for a short period before sporangiophore initiation. Continuous white illumination strongly inhibits microphorogenesis and slightly stimulates macrophorogenesis. Short exposures to white light noticeably inhibit microphorogenesis and stimulate macrophorogenesis when given to mycelia grown for between 90 and 160 h at 14 degrees C or 150 h or more at 10 degrees C. These results indicate the existence in the mycelium of developmental stages for the regulation of sporangiophorogenesis by environmental signals. PMID- 24221511 TI - Photomorphogenesis inPhycomyces: Dependence on environmental conditions. AB - The production of two kinds of vegetative reproductive structures, microphores and macrophores, byPhycomyces blakesleeanus Bgff. depends on plating density, ventilation, asparagine supply, and illumination. Quantitative determinations of these variables lead us to propose a new experimental system for developmental photobiology: standard plastic Petri plates containing 25 ml minimal medium are inoculated with 10(5) viable, heat-activated spores and incubated, unpiled and unsealed, at 22 degrees C. After 4 d microphores are counted and macrophores are weighed. Both microphorogenesis and macrophorogenesis are governed by light. Photosensitivity is a developmental phenomenon which occurs 32 to 68 h after inoculation, just before the beginning of vegetative reproduction in the dark controls. The maximum photosensitivity occurs 48 h after inoculation. PMID- 24221512 TI - Photomorphogenesis inPhycomyces: Fluence-response curves and action spectra. AB - Blue light regulates vegetative reproduction inPhycomyces blakesleeanus Bgff. by inhibiting the development of microphores and stimulating that of macrophores. Fluence-response curves were obtained at twelve different wavelengths. Each response exhibits a two-step ("biphasic") dependence on fluence, as if it resulted from the addition of two separate components with different thresholds, midpoints, and amplitudes. The absolute threshold is close to 10 photons.MUm(2). The threshold fluence of the low-intensity component is about 10(4) times smaller than that of the high-intensity component. The action spectra for each of the two components of the two responses share general similarities, but exhibit significant differences that might be taken to favour four separate photosystems. Additional complexity is indicated by the wavelength dependence of the saturation levels. PMID- 24221513 TI - Antibody localization of extensin in cell walls of carrot storage roots. AB - The accumulation and cross-linking of hydroxyproline-rich glycoproteins (HRGPs) in cell walls of dicotyledonous plants has been correlated with a number of wall strengthening phenomena. Polyclonal antibodies raised against glycosylated extensin-1, the most abundant HRGP in carrot (Daucus carota L.) cell walls, recognize this antigen on gel and dot blots and on thin sections of epoxy embedded carrot-root cell walls. Since wall labeling can be largely reduced by preincubating the antibodies with purified extensin-1, most labeling can be attributed to recognition of this antigen. The remaining label may be the result of recognition of extensin-2, a second carrot HRGP, or other wall components (cellulose, hemicellulose and pectin are not recognized). Extensin-1 label was distributed quite uniformly across the cell wall but was absent from the expanded middle lamella at the intersection of three or more cells and was reduced in the narrow middle lamella between two cells. This distribution is essentially the same as that of cellulose. Because of limitations of this labeling technique, it is not possible to construct a complete model of the structure of the cross linked extensin matrix. Nonetheless, short, linear arrays of gold particles may represent small portions of the extensin matrix or of individual extensin molecules as they are exposed on the surface of sections. These and other results presented here indicate that: a) newly synthesized extensin is added to the wall by intussusception; b) extensin cannot cross the middle lamella separating the walls of adjacent cells; and c) incorporation of extensin is a late event in the development of phloem-parenchyma cell walls in carrot. PMID- 24221514 TI - Physical properties of the cell wall of photoautotrophic suspension cells fromChenopodium rubrum L. AB - Photoautotrophic suspension cells ofChenopodium rubrum were used to determine Donnan potential, charge density and pore-radius distribution in the cell wall. Experiments were done either with turgescent cells or with isolated cell walls. Titration of a cell-wall-generated 9-aminoacridine fluorescence quench with salts of mono- and divalent cations was used to determine Donnan potential and charge density. The experiments and theory were adapted from measurements of membrane surface charges. A tenfold increase in ionic strength, which decreases the repellant forces between charges of the same sign, led to an approximately threefold increase in the measured charge density, thus resulting in a much smaller decrease of the Donnan potential than would be expected if the charge density remained fixed. This decreased influence of ionic strength on the Donnan potential, resulting from the elasticity of the cell wall, was also measurable but less pronounced when the wall of intact cells was stretched by turgor. The porosity of the cell wall was determined by longterm uptake of polyethylene glycols of different molecular weights, and by gel filtration of polyethylene glycols and dextrans as well as mono- and disaccharides using intact suspension cells as matrix. Both methods gave a mean pore diameter of about 4.5 nm and a maximum pore size of 5.5 nm. The resulting pores-size distribution was slightly broader with the latter method. PMID- 24221515 TI - Stimulation of sugar exit from leaf tissues ofVicia faba L. AB - After removal of the lower epidermis, leaf discs ofVicia faba L. were loaded with either [(14)C]sucrose or [(3)H]3-O-methylglucose (3-O-MeG). The exit of preloaded sucrose was strongly stimulated when sucrose was present in the bathing medium, and the exit of 3-O-MeG was also markedly increased in the presence of 3-O-MeG. This specific stimulation exhibited single saturation dependence on the external concentration of sugar (K m=9 mM for sucrose, 5 mM for 3-O-MeG), and was sensitive to low temperature, uncouplers and thiol reagents. Sucrose exit was never affected by 3-O-MeG in the bathing medium. Sucrose did not affect the exit of 3-O-MeG in fresh discs, but promoted this exit in discs previously aged for 12 h, indicating partial external hydrolysis of sucrose in the latter tissues. Ageing also dramatically increased the exit of 3-O-MeG induced by 3-O-MeG but had no effect on the exit of sucrose induced by sucrose. The ability of 53 compounds (pentoses, hexoses, hexose-phosphates, polyols, di- and trisaccharides, phenyl- and nitrophenyl-derivatives, sweeteners) to interact with the sucrose carrier and with the hexose carrier was tested. Sucrose, maltose, alpha-phenylglucoside andp nitrophenyl-alpha-glucoside interacted with the sucrose carrier.D-glucose,D xylose,D-fucose,D-galactose,D-mannose, 3-O-MeG and 2-deoxyglucose interacted with the hexose carrier. PMID- 24221516 TI - Sugar nucleotides dissipate ATP-generated transmembrane pH gradient in Golgi vesicles from suspension-cell protoplasts ofChenopodium rubrum L. AB - A microsomal vesicle fraction (GV) markedly enriched by the Golgi marker enzyme latent inosine diphosphatase (IDPase) has been isolated from photoautotrophic suspension-cell protoplasts ofChenopodium rubrum L. Addition of ATP creates a substantial pH gradient across the GV membrane as measured by accumulation of acridine orange. The GV showed a density of 1.14 g.cm(-3) by equilibrium density centrifugation on sucrose gradients. Coincidence of acridine-orange accumulation and IDPase activity was confirmed on Percoll gradients. Formation of the pH gradient half-saturates at 0.3 mM MgATP, peaks at pH 7, and is competitively inhibited by ADP (k i<=0.1 mM), but not by Pi; it is hardly inhibited by orthovanadate, quickly dissipated by monensink 2=18 nM), nigericin (k 1/2=25 nM), and sluggishly by N-ethylmaleimide (k 1/2~35 MUM). Inhibition by KNO3 (k 1/2~6.7 mM) is incomplete (60%). Uridine 5'-diphosphate (UDP)-glucose, UDP-galactose, but not UDP-mannose and the pertinent sugars, dissipate the ATP-generated pH gradient (k 1/2~10-20 mM UDP-glucose; optimum pH at 7.8). This UDP-glucose activity is accompanied by release of Pi, but not of glucose or sucrose. UDP-glucoseinduced Pi release from the GV saturates (k 1/2=1 mM UDP-glucose; optimum pH at 7) and is completely inhibited by the anion-channel blocker 4,4'-diisothiocyano-2,2' stilbene disulfonic acid (DIDS;k 1/2=140 MUM). The GV incorporates UDP-[U (14)C]glucose into an acid-labile, alkaline-stable macromolecular compound; this process is like-wise inhibited by DIDS. We propose a model including, inter alia, a UDP-glucose/uridine-5'-monophosphate translocator and a phosphate-permeable anion channel to operate in Golgi vesicles ofChenopodium rubrum. PMID- 24221517 TI - Inositol bisphosphate and inositol trisphosphate inhibit cell-to-cell passage of carboxyfluorescein in staminal hairs ofSetcreasea purpurea. AB - pH-buffered carboxyfluorescein (Buffered-CF) alone (control), or Buffered-CF solutions containing one of the following: (1)D-myo-inositol (I); (2)D-myo inositol 2-monophosphate (IP1); (3)D-myo-inositol 1,4-bisphosphate (IP2); (4)D myo-inositol 1,4,5-trisphosphate (IP3); (5)D-fructose 2,6-diphosphate (F-2,6P2) were microinjected into the terminal cells of staminal hairs ofSetcreasea purpurea Boom. Passage of the CF from this terminal cell along the chain of cells towards the filament was monitored for 5 min using fluorescence microscopy and quantified using computer-assisted fluorescence-intensity video analysis. Cell-to cell transport of CF in hairs microinjected with Buffered-CF containing either I, IP1 or F-2,6P2 was similar to that in hairs microinjected with Buffered-CF only. On the other hand, cell-to-cell transport of CF in hairs microinjected with Buffered-CF containing either IP2 or IP3 was inhibited. These results indicate that polyphosphoinositols may be involved in the regulation of intercellular transport of low-molecular-weight, hydrophilic molecules in plants. PMID- 24221518 TI - Co-ordinated regulation of chitinase and beta-1,3-glucanase in bean leaves. AB - Ethylene induced chitinase (EC 3.2.1.14) and beta-1,3-glucanase (EC 3.2.1.29) to a similar extent in primary leaves of bean seedlings (Phaseolus vulgaris cv. Saxa). Both enzymes were purified from ethylene-treated leaves, and monospecific antibodies were raised aginst them. Ethylene treatments strongly increased the amount of immunore-active chitinase and beta-1,3-glucanase. Ethylene enhanced synthesis of chitinase in vivo, as tested by immunoprecipitation after pulse labelling with [(35)S]methionine. RNA was isolated from bean leaves and translated in a rabbit reticulocyte lysate system in vitro. The chitinase and the beta-1,3-glucanase antiserum each precipitated a single polypeptide from the translation products. The precipitated polypeptides were 1500 and 4000 daltons larger, respectively, than native chitinase and native beta-1,3-glucanase, indicating that the two enzymes were synthesized as precursors in vitro. The translatable mRNAs for both enzymes increased at least tenfold within 2 h in response to a treatment with ethylene. When ethylene was withdrawn after 8 h of incubation, the translatable mRNAs for both enzymes decreased somewhat more slowly, reaching the basal level about 25 h later. In all cases, there was a close correlation between the levels of translatable mRNA for chitinase and beta 1,3-glucanase. A putative beta-1,3-glucanase cDNA clone, pCH16, was isolated by hybrid-selected translation. The amount of beta-1,3-glucanase mRNA, as measured by RNA blot analysis using pCH16 as a probe, increased rapidly in response to ethylene and decreased again after withdrawal of ethylene, indicating that the amount of hybridizable RNA and of translatable mRNA for beta-1,3-glucanase were correlated. In conclusion, the results indicate that chitinase and beta-1,3 glucanase are regulated co-ordinately at the level of mRNA. PMID- 24221519 TI - Transient reduction of responsiveness of blue-light-mediated hair-whorl morphogenesis inAcetabularia mediterranea induced by blue light. AB - After a prolonged period of red light the formation of a new whorl of lateral hairs can be induced inAcetabularia mediterranea Lamouroux (=A. acetabulum (L.) Silva) by a pulse of blue light. It has previously been shown that the response to blue light obeys the law of reciprocity. In this paper we demonstrate that the responses to blue light are additive only within 10 min after the onset of blue light treatment, since the responsiveness of the cells is also affected by blue light. One hour after a short blue-light pulse the response to a second blue light pulse has come to a minimum. After that, the responsiveness is restored in a refractory period of several hours. The fluenceresponse curves for hair-whorl formation at the time of minimum responsiveness are shifted parallel to the original fluence-response curves without preirradiation. Again, the law of reciprocity applies. This indicates an increased light requirement only for the same degree of hair-formation response. The sensitivity to blue light of the "reduction of responsiveness" response is higher by a factor of about 50 than the "induction of hairformation" response. PMID- 24221520 TI - Characterization of phloem exudation from castor-bean cotyledons. AB - Exudate was collected fromRicinus communis L. cotyledons after cutting the hypocotyl. It contained high levels of sucrose and potassium, a low level of calcium, and a pH of approx. 7.5. After application of [(14)C] sucrose to the cotyledons, radioactivity could be recovered from the exudate, indicating that the exudate was derived from the phloem. Using data from a number of individual seedlings, correlations between loading rates of sucrose, translocation rates, and sucrose and potassium contents were analyzed. A positive correlation was found between the rate of sucrose loading and the rate of sucrose exudation, whereas a negative correlation existed between the contents of sucrose and potassium in the phloem. PMID- 24221521 TI - Enhanced nodule initiation on alfalfa by wild-typeRhizobium meliloti co inoculated withnod gene mutants and other bacteria. AB - Nodule formation on alfalfa (Medicago sativa L.) roots was determined at different inoculum dosages for wild-typeRhizobium meliloti strain RCR2011 and for various mutant derivatives with altered nodulation behavior. The number of nodules formed on the whole length of the primary roots was essentially constant regardless of initial inoculum dosage or subsequent bacterial multiplication, indicative of homeostatic regulation of total nodule number. In contrast, the number of nodules formed in just the initially susceptible region of these roots was sigmoidally dependent on the number of wild-type bacteria added, increasing rapidly at dosages above 5.10(3) bacteria/plant. This behavior indicates the possible existence of a threshold barrier to nodule initiation in the host which the bacteria must overcome. When low dosages of the parent (10(3) cells/plant) were co-inoculated with 10(6) cells/plant of mutants lacking functionalnodA, nodC, nodE, nodF ornodH genes, nodule initiation was increased 10- to 30-fold. Analysis of nodule occupancy indicated that these mutants were able to help the parent (wild-type) strain initiate nodules without themselves occupying the nodules. Co-inoculation withR. trifolii orAgrobacterium tumefaciens cured of its Ti plasmid also markedly stimulated nodule initiation by theR. meliloti parent strain. Introduction of a segment of the symbiotic megaplasmid fromR. meliloti intoA. tumefaciens abolished this stimulation.Bradyrhizobium japonicum and a chromosomal Tn5 nod(-) mutant ofR. meliloti did not significantly stimulate nodule initiation when co-inoculated with wild-typeR. meliloti. These results indicate that certainnod gene mutants and members of theRhizobiaceae may produce extracellular "signals" that supplement the ability of wild-typeR. meliloti cells to induce crucial responses in the host. PMID- 24221522 TI - Sequence analysis of proteolytic fragments of 124-kilodalton phytochrome from etiolatedAvena sativa L.: Conclusions on the conformation of the native protein. AB - Proteolytic fragments were obtained by limited proteolysis of 124-kDa (kilodalton) phytochrome from etiolatedAvena sativa using trypsin, endoproteinase Lys-C, endoproteinase-Glu-C and subtilisin. The fragments were separated by sodium dodecyl sulfate gel electrophoresis, blotted onto activated glass-fiber sheets and investigated by amino-acid sequencing in a gas-phase sequencer. Determination of N-terminal sequences in three to six Edman degradation steps allowed the exact localization of the fragments within the published entire amino acid sequence of 124-kDaAvena phytochrome (H.P. Hershey, R.F. Barker, K.B. Idler, J.L. Lissemore, P.H. Quail (1985), Nucleic Acids Res.13, 8543-8559). From the knowledge of the exact sites for preferred proteolytic cleavage of undenatured phytochrome, conclusions on the conformation of the phytochrome protein were drawn. Sites of preferred cleavage are considered to be freely exposed to the environment whereas potential cleavage sites which are resistant to proteolysis over a long time are considered to be localized in the interior of the native phytochrome. Two different sites which are exposed in the far-red-absorbing form but not in the red-absorbing form of phytochrome are localized at amino-acid residues 354 and 753, respectively. The N-terminal region which is exposed only in the red-absorbing form stretches only as far as amino-acid residue 60. PMID- 24221523 TI - Hormonal regulation of ripening in the strawberry, a non-climacteric fruit. AB - Anthocyanin accumulation is one measure of ripening in the strawberry (Fragaria ananassa Duch.), a non-climacteric fruit. Neither aminoethoxyvinylglycine, an inhibitor of 1-aminocyclopropane carboxylic acid synthase, nor inhibitors of ethylene action (silver, norbornadiene) affected anthocyanin accumulation in ripening fruit. When the achenes were removed from one half of an unripe fruit there was an accelerated accumulation of anthocyanin and induction of phenylalanine ammonia lyase on the de-achened portion of the ripening fruit. These effects of achene removal could be prevented by the application of the synthetic auxins 1-naphthaleneacetic acid or 2,4-dichlorophenoxyacetic acid to the de-achened surface. The introduction of 1-naphthalene acetic acid into intact unripe strawberry fruit through the peduncle delayed their subsequent ripening, as measured by the accumulation of anthocyanin, loss of chlorophyll and decrease in firmness. These findings suggest that the decline in the concentration of auxin in the achenes as strawberry fruit mature modulates the rate of fruit ripening. PMID- 24221524 TI - The in-vivo response of the ribulose-1,5-bisphosphate carboxylase activation state and the pool sizes of photosynthetic metabolites to elevated CO2 inPhaseolus vulgaris L. AB - The short-term, in-vivo response to elevated CO2 of ribulose-1,5-bisphosphate carboxylase (RuBPCase, EC 4.1.1.39) activity, and the pool sizes of ribulose 1,5 bisphosphate, 3-phosphoglyceric acid, triose phosphates, fructose 1,6 bisphosphate, glucose 6-phosphate and fructose 6-phosphate in bean were studied. Increasing CO2 from an ambient partial pressure of 360-1600 MUbar induced a substantial deactivation of RuBPCase at both saturating and subsaturating photon flux densities. Activation of RuBPCase declined for 30 min following the CO2 increase. However, the rate of photosynthesis re-equilibrated within 6 min of the switch to high CO2, indicating that RuBPCase activity did not limit photosynthesis at high CO2. Following a return to low CO2, RuBPCase activation increased to control levels within 10 min. The photosynthetic rate fell immediately after the return to low CO2, and then increased in parallel with the increase in RuBPCase activation to the initial rate observed prior to the CO2 increase. This indicated that RuBPCase activity limited photosynthesis while RuBPCase activation increased. Metabolite pools were temporarily affected during the first 10 min after either a CO2 increase or decrease. However, they returned to their original level as the change in the activation state of RuBPCase neared completion. This result indicates that one role for changes in the activation state of RuBPCase is to regulate the pool sizes of photosynthetic intermediates. PMID- 24221525 TI - Influence of acetate and malonate on the production of 1,8-dihydroxyanthracene derivatives in suspension cultures ofRhamnus purshiana. AB - Acetate and malonate, basic precursors in the biosynthesis of polyketides, were added to suspension cultures ofRhammus purshiana DC. It was found that the production of anthra-derivatives (i.e. 1,8-dihydroxyanthraquinones, anthrones and or dianthrones) in these cultures was significantly stimulated by malonate, while addition of acetate had an inhibitory effect under similar conditions. PMID- 24221526 TI - Light-stimulated respiration in the green algaDunaliella tertiolecta: Involvement of the ultraviolet/blue-light photoreceptor(s) and phytochrome? AB - Starch breakdown and respiratory O2 uptake in the green algaDunaliella tertiolecta (Butcher) are stimulated not only by blue, but also by red light. In the present study, attempts are described to identify the photoreceptor(s) involved. Fluence rate-response curves with different slopes in the ultraviolet (UV)/blue and in the red spectral region as well as differences in the kinetics and in the unfluence of dark pre-incubation on the stimulation of respiratory O2 uptake by blue and red light strongly indicate the action of two photoreceptors. Since the effect of red light shows some far-red reversibility, and since simultaneous irradiation with red and far-red light decreases the effectiveness of red light, the involvement of phytochrome - in addition to the UV/blue photoreceptor(s) - is suggested in the light-stimulated respiration inDunaliella. PMID- 24221527 TI - Control by phytochrome of the appearance of ribulose-1,5-bisphosphate carboxylase and the mRNA for its small subunit. AB - We have measured levels of ribulose-1,5-bisphosphate carboxylase (RuBPCase) and levels of in-vitro-translatable mRNA for the small subunit (SSU) of RuBPCase up to 96 h after sowing in mustard (Sinapis alba L.) cotyledons, in order to investigate to what extent the rate of enzyme synthesis is related to the level of SSU-mRNA. Both enzyme and mRNA level are controlled strongly by phytochrome, but the rate of RuBPCase accumulation was found to be unrelated to the level of translatable SSU-mRNA. As an example, it was found that the amount of SSU-mRNA in far-red light (FR)-grown mustard seedlings doubles between 54 and 84 h after sowing while the rate of RuBPCase accumulation remains constant over this period. Since the holoenzyme shows zero turnover during this period it is concluded that the rate of enzyme synthesis remains constant although the level of SSU-mRNA increases strongly. Following an FR->dark transition, with different levels of physiologically active phytochrome (Pfr) established at the end of the light period, no correlation was found between the time course of mRNA levels in darkness and the rate of enzyme synthesis. Rather, the data indicate that there is at least one translational or post-translational regulatory step which is also phytochrome-dependent. It is concluded that coarse control of the appearance of translatable SSU-mRNA is essential for RuBPCase to appear at a high rate but that fine tuning by phytochrome of the actual appearance of RuBPCase is not transcriptional. PMID- 24221530 TI - Occlusion of vertebral artery due to transverse canal osteochondroma. PMID- 24221531 TI - Walk the line: from diffusion imaging to the microstructure of the brain. PMID- 24221532 TI - Cingulum injury by external ventricular drainage procedure: diffusion tensor tractography study. PMID- 24221533 TI - Assessment of abstract reasoning abilities in alcohol-dependent subjects: an fMRI study. AB - INTRODUCTION: Chronic alcohol abuse has been traditionally associated with impaired cognitive abilities. The deficits are most evident in higher order cognitive functions, such as abstract reasoning, problem solving and visuospatial processing. The present study sought to increase current understanding of the neuropsychological basis of poor abstract reasoning abilities in alcohol dependent subjects using functional magnetic resonance imaging (fMRI). METHODS: An abstract reasoning task-based fMRI study was carried out on alcohol-dependent subjects (n = 18) and healthy controls (n = 18) to examine neural activation pattern. The study was carried out using a 3-T whole-body magnetic resonance scanner. Preprocessing and post processing was performed using SPM 8 software. RESULTS: Behavioral data indicated that alcohol-dependent subjects took more time than controls for performing the task but there was no significant difference in their response accuracy. Analysis of the fMRI data indicated that for solving abstract reasoning-based problems, alcohol-dependent subjects showed enhanced right frontoparietal neural activation involving inferior frontal gyrus, post central gyrus, superior parietal lobule, and occipito-temporal gyrus. CONCLUSIONS: The extensive activation observed in alcohol dependents as compared to controls suggests that alcohol dependents recruit additional brain areas to meet the behavioral demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting decreased neural efficiency of relevant brain networks or compensatory mechanisms for the execution of task for showing an equivalent performance. PMID- 24221535 TI - Refinement of the prediction of N-acetyltransferase 2 (NAT2) phenotypes with respect to enzyme activity and urinary bladder cancer risk. AB - Polymorphisms of N-acetyltransferase 2 (NAT2) are well known to modify urinary bladder cancer risk as well as efficacy and toxicity of pharmaceuticals via reduction in the enzyme's acetylation capacity. Nevertheless, the discussion about optimal NAT2 phenotype prediction, particularly differentiation between different degrees of slow acetylation, is still controversial. Therefore, we investigated the impact of single nucleotide polymorphisms and their haplotypes on slow acetylation in vivo and on bladder cancer risk. For this purpose, we used a study cohort of 1,712 bladder cancer cases and 2,020 controls genotyped for NAT2 by RFLP-PCR and for the tagSNP rs1495741 by TaqMan((r)) assay. A subgroup of 344 individuals was phenotyped by the caffeine test in vivo. We identified an 'ultra-slow' acetylator phenotype based on combined *6A/*6A, *6A/*7B and *7B/*7B genotypes containing the homozygous minor alleles of C282T (rs1041983, *6A, *7B) and G590A (rs1799930, *6A). 'Ultra-slow' acetylators have significantly about 32 and 46 % lower activities of caffeine metabolism compared with other slow acetylators and with the *5B/*5B genotypes, respectively (P < 0.01, both). The 'ultra-slow' genotype showed an association with bladder cancer risk in the univariate analysis (OR = 1.31, P = 0.012) and a trend adjusted for age, gender and smoking habits (OR = 1.22, P = 0.082). In contrast, slow acetylators in general were not associated with bladder cancer risk, neither in the univariate (OR = 1.02, P = 0.78) nor in the adjusted (OR = 0.98, P = 0.77) analysis. In conclusion, this study suggests that NAT2 phenotype prediction should be refined by consideration of an 'ultra-slow' acetylation genotype. PMID- 24221534 TI - First demonstration of resolution of an infundibulum by direct treatment of the arterial wall with Pipeline flow-diverting stent. AB - INTRODUCTION: Infundibula are symmetrical funnel-shaped widening, measuring more than 3 mm at its base with the branch artery arising from its apex. The pathological significance of this entity remains controversial. Although a relatively common appearance in otherwise normal angiograms, they have occasionally been described to progress into saccular aneurysms or directly rupture. METHODS/RESULTS: We describe the first case of a disappearing infundibulum after a flow diverting stent was deployed across the infundibulum during the treatment of an adjacent aneurysm. CONCLUSIONS: We concur in the view that infundibula are at least pre-pathological lesions that may in certain circumstances require consideration for treatment. Our case for the first time offers a potential treatment option for such situations. PMID- 24221536 TI - Recent developments in in vitro toxicology: perspectives of European research and Tox21. PMID- 24221537 TI - Regeneration of fertile plants from protoplasts of sunflower (Helianthus annuus L.). AB - Sunflower hypocotyl protoplasts (Helianthus annuus L.) from 5 PIONEER genotypes (PT024, SMF3, EMIL, HA300*PT024, VK5F) and 1 public line (RHa 274) formed colonies at frequencies of up to 60% when plated in 0.25ml agarose beads in a modified L4 medium (Lenee and Chupeau 1986) containing 3mg/l NAA, 1mg/l BA and 0.1mg/l 2,4-D, and 1000mg/l casamino acids. Protoplast-derived colonies grew slowly into calli. Organogenesis was obtained from callus of PT024 on a MS medium containing NAA and BA at 1mg/l and GA at 0.1mg/l. Freshly excised shoots were induced to root by an IAA treatment. Regenerated plants were transferred to the greenhouse and seed was harvested within 7 months of the initial protoplast isolation. PMID- 24221538 TI - Selection for Fusarium wilt disease resistance from regenerants derived from leaf callus of strawberry. AB - Resistant lines of strawberry to the fungal wilt disease caused by Fusarium oxysporum f. sp. fragariae were selected strawberry plants regenerated from leaf derived callus tissues. Regenerants were transplanted to a field heavily infested with this pathogen, and normally growing plants were selected as the putative resistant lines. Daughter plants produced vegetatively through runner formation of the lines were similarly tested in the pathogen-infested field over an additional three generations. Finally, two resistant lines were obtained from a total of 1,225 regenerants. The stable propagation of disease resistance in these lines was confirmed by directly inoculating the daughter plants with the pathogen and planting in a pathogen-infested soil. All of the control plants were efficiently infected and died within one month. The isolated plant lines grew and developed runners even after direct inoculation and produced daughter plants in this soil. Thus, the present study demonstrated the existence of somaclonal variation for disease resistance against a soil-borne fngal pathogen. PMID- 24221539 TI - Retention of the capacity to produce plants from protoplasts in cryopreserved cell lines of rice (Oryza sativa L.). AB - A method is described for cryopreservation of cell suspension lines of rice (Oryza sativa L.) for use in protoplast research and as a way of retaining desirable characteristics of cell lines. The procedure involves pre-culture with mannitol, addition of a cryoprotectant solution of sucrose, dimethyl sulfoxide, glycerol and L-proline, two step freezing and storage in liquid nitrogen. Cells have been preserved for up to 14 months (the longest period tried in these experiments). Cryopreserved cells proliferated after plating on solid medium and new cell suspensions could be initiated within 15 days. Viable protoplasts, capable of divisions and callus formation, could be obtained 15-21 days after thawing. Variation between cell lines in terms of recovery rate after cryopreservation occurred. Differences between cell lines in plating efficiencies on solidified medium, however, contributed to this variation. Protoplasts from cryopreserved regenerable cell lines gave rise to embryogenic callus from which plants could be regenerated. These plants developed to maturity. A transformed cell line was also cryopreserved and it had retained the hygromycin resistance and regenerative capacity of the original cell line. PMID- 24221540 TI - Relation of the developmental stage of zygotic embryos of yellow-poplar to their somatic embryogenic potential. AB - The goal of the study was to characterize the optimal developmental stage of zygotic embryo expiants of the hardwood forest tree species yellow-poplar (Liriodendron tulipifera L.) for the initiation of embryogenic cultures, using morphological measurements and polypeptide profiles of the embryos. Developing zygotic embryos from seeds of six full-sib families, collected every two weeks from 4 weeks postpollination until seed maturity (18 weeks postpollination) were divided into 2 subsamples for each collection date. One group was used to initiate tissue cultures. Embryos in the other group were measured (total length, cotyledon length and hypocotyl thickness) and soluble polypeptide profiles of the embryos were analyzed by SDS-polyacrylamide gel electrophoresis. Potential of an expiant to produce an embryogenic culture peaked during the eighth week following pollination, with an average of 28% of the expiants producing proembryogenic masses, and declined to near zero for mature zygotic embryos. The maximum embryogenic potential corresponded to the globular stage of embryo developmet. Soluble protein profiles of zygotic embryos from 5 sampling dates indicated that decline in embryogenic potential appeared to parallel an increase in the level of a polypeptide of approximately 55 kDa, possibly a storage protein. PMID- 24221541 TI - Effect of plant growth regulators on somatic embryogenesis in leaf cultures of Coffea canephora. AB - The effects of plant growth regulators on somatic embryogenesis were studied in leaf cultures of Coffea canephora. The maximum number of somatic embryos were obtained on media that contained only cytokinin as a plant growth regulator. All of the auxins tested (NAA, IBA, IAA and 2, 4-D) inhibited the formation of embryos. The optimal concentration of each cytokinin (2-iP, BA and kinetin) for somatic embryogenesis was 5 MUM. Under optimal conditions, each explant formed more than 100 embryoids with little callus and few adventitious roots. Embryoids were formed only at the cut edges of the leaf discs. Cytokinins were absorbed only at the cut edges of leaf discs that were in contact with the medium, and were not transported to other parts of the explant. PMID- 24221542 TI - Regeneration of Cladrastis lutea (Fabaceae) via somatic embryogenesis. AB - Immature embryos from 5 Cladrastis lutea (Michx.) K. Koch (yellowwood) trees were initially cultured on modified Schenk and Hildebrandt medium (SH) containing either 4.5, 9.0, 13.5 or 23 MUM 2,4-D. One-third of the explants were transferred to SH medium supplemented with 25.0 MUM NAA after 2 and 3 weeks respectively. The remaining explants were incubated on the initial 2,4-D containing media for 6 weeks. Groups of somatic embryos formed directly only at the proximal end of cotyledons; only a few formed as single embryos. The greatest numbers were formed from zygotic embryos explanted from 6-8 weeks post-anthesis and initially cultured on medium containing 9 or 13 MUM 2,4-D. However, all treatments supported somatic embryogenesis. In the second year, explants were initially cultured on SH medium containing either 9.0, 13.5, or 23 MUM 2,4-D and then transferred to SH medium containing 4.0 MUM ABA after 2 or 3 weeks. ABA did not affect the development of somatic embryos. Six of 21 somatic embryos germinated on half-strength SH medium without growth regulators. Three entire plantlets were formed, but only one was established in soil. PMID- 24221543 TI - Transient expression from microprojectile-mediated DNA transfer in pinus taeda. AB - Transfer of plasmid DNA to Pinus taeda L. (loblolly pine) cotyledon cells by microprojectile bombardment has been demonstrated using beta-glucuronidase (GUS). GUS histochemical staining indicated active enzyme in localized centers (blue spots) 24 hours after bombardment. GUS expression declined during subsequent culture, but remained detectable in meristematic tissue 62 days post-bombardment, however, transgenic shoots were not recovered. Localized GUS expression events resulted predominantly from single-cell events containing one microprojectile. The staining pattern was complex, with indigo found both in the central target cell and in adjacent cells. Cellular damage sustained by GUS-positive cells ranged from undetectable to sufficiently extensive to cause cell death. Microprojectile bombardment provides a useful method to assay transient gene expression in loblolly pine and has potential for the production of transgenic plants in pine. PMID- 24221544 TI - Transient expression of the beta-glucuronidase gene in embryogenic callus of Picea mariana following microprojection. AB - A microprojection protocol using the DuPont Biolistic(TM) particle delivery system and the beta-glucuronidase (GUS) reporter gene fused with the 35S promoter of Cauliflower mosaic virus (CaMV) was developed for Picea mariana callus. Comparison of four tungsten microprojectile sizes showed the highest transient gene expression with 1.11MUm diameter particles. Adsorption of DNA on the microcarriers using calcium chloride led to higher GUS gene activity than using polyethylene glycol. GUS gene activity in P. mariana was the highest when cells were treated 5 and 6 days after subculturing to fresh media. The wheat ABA inducible Em gene promoter yielded 4.5 times higher GUS gene activity than the 35S CaMV promoter. Comparison of transient GUS gene expression among 10 P. mariana embryogenic cell lines from six different open-pollinated families showed comparable gene activity, with the exception of one family showing no GUS gene activity. PMID- 24221545 TI - Regeneration and Agrobacterium-mediated transformation of chrysanthemum. AB - A method has been developed to regenerate shoots directly from leaf pieces of the autumn flowering chrysanthemum Dendranthema indicum (L.) Des Moul (genotype Korean). Transgenic plants of this genotype were generated using transformation mediated by the disarmed strain of Agrobacterium tumefaciens LBA4404, containing either pKIWI110 or pGA643. Both pKIWI110 and pGA643 contain the selectable marker gene neomycin phosphotransferase II (NPTII) and pKIWI110 also contains the reporter gene beta-D-glucuronidase. Leaf pieces inoculated with pKIWI110 produced zones of blue cells two days after inoculation. Shoots from leaf pieces inoculated with pGA643 were selected on kanamycin. PCR and Southern analysis of shoots that were able to root on kanamycin confirmed the presence of the NPTII gene in the plant genome. PMID- 24221546 TI - Plant regeneration from protoplasts of wild rice (Oryza rufipogon Griff.). AB - Embryogenic callus initiated from basal segments of micropropagated shoots of Oryza rufipogon were used to initiate cell suspension cultures. After approximately 3 months these cultures were capable of yielding large numbers of protoplasts which underwent sustained division in agarose-solidified medium at a frequency comparable to that observed with Japonica rice protoplasts in previous studies. O. rufipogon plants were reproducibly regenerated from the protoplast derived callus and are currently being grown to maturity. This is the first report of plant regeneration from protoplasts of a wild species of Oryza. PMID- 24221547 TI - Stimulation of shoot regeneration from cotyledons of Helianthus annuus by the ethylene inhibitors, silver and cobalt. AB - The effects of CoCl2, AgNO3 and ethylene released by exogenous 2 chloroethylphosphonic acid (Ethephon), were studied on shoot regeneration from cotyledons of Helianthus annuus cv. E8206R, a poorly regenerative cultivar. Inhibition of ethylene biosynthesis by CoCl2, at concentrations of 20 MUK, provoked a substantial enhancement of shoot regeneration (30 %): the control was poorly regenerative. However, CoCl2 had no effect when Ethephon was supplied. Inhibition of ethylene action by AgNO3, at concentrations of 10-25 MUM, caused a significant increase in plant regeneration: 25 % instead of 1.2 % in the control. Furthermore, addition of Ethephon to AgNO3-treated tissues failed to reduce the stimulation of shoot regeneration caused by AgNO3. On the basis of these findings, it is suggested that ethylene inhibits the regeneration process from cotyledons of sunflower. PMID- 24221548 TI - Agrobacterium-mediated transformation of pepino and regeneration of transgenic plants. AB - Regeneration of pepino (Solanum muricatum Ait.) shoots was achieved both by organogenesis and by embryogenesis. Shoots derived via organogenesis were easily rooted and most regenerated plants appeared phenotypically normal. Transgenic plants were obtained using the binary vector pKIWI110 in the avirulent Agrobacterium tumefaciens strain LBA4404. Optimization of transformation protocols was rapidly achieved by monitoring early expression of the GUS (beta-D glucuronidase) reporter gene carried on pKIWI110. Transgenic plants expressed GUS and selectable marker genes for kanamycin resistance and chlorsulfuron resistance. PCR (polymerase chain reaction) and Southern analysis provided molecular evidence for transformation. PMID- 24221549 TI - Effect of cellulases on spontaneous fusion of maize protoplasts. AB - The effect of protoplast-isolating enzymes on spontaneous fusion of maize protoplasts (Zea mays L. cv. Black Mexican Sweet) was investigated using a convenient ethidium bromide nuclear staining procedure. After 2-2.5 hour digestion in an enzyme solution containing 1% Cellulysin, 0.5% Rhozyme, and 0.02% Pectolyase Y-23, 50-75% of the protoplasts contained multiple nuclei. The cellulase Cellulysin was identified as the factor causing the spontaneous protoplast fusion; when Cellulysin was replaced by CELF cellulase, most protoplasts were uninucleate. Calcium and other components in the enzyme solution did not affect spontaneous fusion. Cellulysin also increased the percentage of multinucleate protoplasts from rice and asparagus suspensions. Presence of multiple nuclei might affect genetic manipulations involving protoplasts. PMID- 24221550 TI - Cytochrome P-450 mediated O-dealkylation of 7-alkoxycoumarins in liver microsomes from rainbow trout (Salmo gairdneri). AB - Evidence has recently been presented for variation in the inducibility of various 7-alkoxycoumarin-O-dealkylase activities in liver microsomes from a number of mammalian species by beta-naphthoflavone (betaNF). In the present study we have investigated the inducibility of hepatic microsomal 7-methoxycoumarin-O demethylase, 7-ethoxycoumarin-O-deethylase, 7-propoxycoumarin-O-depropylase and 7 butoxycoumarin-O-debutylase activities in rainbow trout by betaNF. O-demethylase activity was increased approximately 17-fold, O-deethylase and O-depropylase activities approximately 9-fold and O-debutylase activity approximately 25-fold. The kinetics of the various hepatic microsomal 7-alkoxycoumarin-O-dealkylase activities were investigated in control and betaNF-treated rainbow trout. The O demethylase-, O-depropylase- and O-debutylase activities exhibited monophasic Michaelis-Menten kinetics in liver microsomes from both control and betaNF treated rainbow trout, whereas the O-deethylase activity exhibited biphasic Michaelis-Menten kinetics in control liver microsomes and monophasic Michaelis Menten kinetics in liver microsomes from betaNF-treated rainbow trout. PMID- 24221551 TI - Catecholestrogens inhibit dopamine methylation in the gonadotrops of the African catfish,Clarias gariepinus. AB - Isolated gonadotrops of the African catfish,Clarias gariepinus, were incubated with dopamine (DA) and/or catecholestrone and the activity of the enzyme catechol O-methyltransferase (COMT) was determined by measuring the methylated products. From the apparent Km values for DA and catecholestrone of 0.4-1.3 MUM and 17.9 25.2 MUM respectively, it was concluded that catecholestrone is a better substrate for the enzyme COMT, compared to DA. Moreover, the methylation of DA is inhibited by comparatively low concentrations of catecholestrone. PMID- 24221552 TI - Autonomic innervation of the ovary of the Atlantic cod,Gadus morhua. AB - The autonomic innervation of the ovary of the Atlantic cod was investigated using histochemical and physiological/pharmacological methods. The paired ovary receives autonomic innervation via branches of the posterior splanchnic nerve (vesicular nerve).Histochemical studies demonstrated vasoactive intestinal polypeptide (VIP)-immunoreactive, 5-hydroxytryptamine-immunoreactive and adrenergic nerve fibers, but a number of antisera raised against other peptides failed to reveal any specific reaction in the tissue preparations. It is concluded that the cod ovary receives a double antagonistic autonomic innervation of excitatory cholinergic fibers and non-adrenergic inhibitory fibers. The nature of the inhibitory neurotransmitter is not known. PMID- 24221553 TI - Induction of metallothionein synthesis in rainbow trout,Salmo gairdneri, during long-term exposure to waterborne cadmium. AB - Rainbow trout were exposed to 200 MUg cadmium/l in the water during four months at 6-10 degrees C. The liver, kidney and gills were analyzed for cadmium, copper, zinc, metallothionein and metallothionein mRNA. Cadmium accumulated in all three organs and reached the highest concentration in the kidney. The tissue zine and copper concentrations showed no major alterations during the experiment. The cytosolic distribution of cadmium, copper and zinc was followed during four months of exposure by Sephadex G-75 chromatography. It was found that cadmium was predominantly associated with proteins of an apparent molecular vieght of 10,000 daltons. These proteins were further identified as metallothioneins after fast protein liquid chromatography on a Mono-Q column. The metallothionein concentration was significantly higher in liver of exposed fish than in control fish after only one month. The kidneys reached significantly elevated levels of metallothionein in the exposed group after three months. In the gills, elevated metallothionein concentrations were observed after four months of exposure. After four months of exposure, the metallothionein mRNA content of liver and kidney was analyzed using a rainbow trout anti-sense RNA probe. Elevated MT mRNA levels were observed in both kidney and liver. These results demonstrate thatde novo synthesis of metallothionein is induced by cadmium in rainbow trout after exposure to the metalvia water. PMID- 24221554 TI - Mitochondrial enzyme and Na(+), K (+)-ATPase activity, and ion regulation during parr-smolt transformation of Atlantic salmon (Salmon salar). AB - Atlantic salmon (Salmo salar) exposed to either simulated natural photoperiod (SNP) or continuous light (L24) were used to examine developmental changes in the presence and absence, respectively, of the parrsmolt transformation. Plasma osmolarity and ion concentrations were unaffected by photoperiod treatment. Gill Na(+), K(+)-ATPase specific activity increased 150% between February and June in SNP fish and was low and unchanged in L24 fish. Kidney Na(+), K(+)-ATPase specific activity varied within similar, narrow limits in both groups. Citrate synthase of liver, gill and kidney, expressed as specific activity or activity/g total body weight (relative activity), increased 25-60% between March and June in SNP fish. With the exception of kidney relative activity, citrate synthase activity declined to initial (March) levels by August. Liver, gill and kidney cytochrome c oxidase activity of the SNP group underwent similar though less marked changes. Liver, gill and kidney citrate synthase and cytochrome c oxidase activities of the L24 group remained relatively constant between March and August, and where significant differences occurred, they were lower than those of the SNP group. These results indicate that respiratory capacities of the liver, gill and kidney increase in smolls concurrent with preparatory osmoregulatory changes, and subsequently decline. The findings are consistent with a hypothesized transient increase in catabolic activity during the parr-smolt transformation that may be due to the metabolic demands of differentiation. PMID- 24221555 TI - Influence of salinity on the energetics of gill and kidney of Atlantic salmon (Salmo salar). AB - The effect of seawater acclimation and adaptation to various salinities on the energetics of gill and kidney of Atlantic salmon (Salmo salar) was examined. Smolts and non-smolts previously reared in fresh water were exposed to a rapid increase in salinity to 30 ppt. Plasma osmolarity, [Na(+)], [Cl(-)], [K(+)] and [Mg(++)] increased in both groups but were significantly lower in smolts than non smolts. Gill Na(+), K(+)-ATPase specific activity, initially higher in smolts, increased in both groups after 18 days in seawater. Kidney Na(+), K(+)-ATPase specific activity was not affected by salinity in either group. Gill and kidney citrate synthase specific activity was not affected by seawater exposure in smolts but decreased in non-smolts. In a second experiment, Atlantic salmon smolts reared in fresh water were acclimated to 0, 10 or 30 ppt seawater for 3 months at a temperature of 13-14 degrees C. Gill Na(+), K(+)-ATPase was positively correlated with salinity, displaying 2.5- and 5-fold higher specific activity at 10 and 30 ppt, respectively, than at 0 ppt. Kidney Na(+), K(+)-ATPase specific activity was not significantly affected by environmental salinity. Citrate synthase and cytochrome c oxidase specific activities in gill were slightly (6-13%) lower at 10 ppt than at 0 and 30 ppt, whereas kidney activities were lowest at 30 ppt. Oxygen consumption of isolated gill filaments was significantly higher when incubated in isosmotic saline and at 30 ppt than at 0 ppt, but was not affected by the prior acclimation salinity. The results indicate that although high salinity induces increased gill Na(+), K(+)-ATPase activity, it does not induce substantial increases in metabolic capacity of gill or kidney. PMID- 24221556 TI - T3 enhancement ofin vitro estradiol-17beta secretion by oocytes of rainbow trout,Salmo gairdneri, is dependent on cAMP. AB - The cellular mechanism of action of 3,5,3'-triiodo-L-thyronine (T3) in enhancing SG-G100 gonadotropin-induced ovarian secretion of 17beta-estradiol (E2) was studiedin vitro using oocyte follicular preparations of rainbow trout. The dependence of the T3 stimulatory action on the level of intracellular 3',5' cyclic adenosine monophosphate (cAMP) was shown in experiments in which forskolin or dibutyryl cAMP enhanced E2 secretion. In the presence of partially purified salmon gonadotropin (SG-G100), T3 stimulation of E2 secretion was prevented by theophylline, suggesting that T3 may exert part of its stimulatory action by inhibiting phosphodiesterase. PMID- 24221557 TI - Assessment of the hydrogeochemistry and groundwater quality of the Tarim River Basin in an extreme arid region, NW China. AB - The concentrations of the major and trace elements in the groundwater of the Tarim River Basin (TRB), the largest inland river basin of China, were analyzed before and during rainy seasons to determine the hydrogeochemistry and to assess the groundwater quality for irrigation and drinking purposes. The groundwater within the TRB was slightly alkaline and characterized by high ionic concentrations. The groundwater in the northern sub-basin was fresh water with a Ca(2+)-HCO3(-) water type, whereas the groundwater in the southern and central sub-basins was brackish with a Na(+)-Cl(-) water type. Evaporite dissolution and carbonate weathering were the primary and secondary sources of solutes in the groundwater within the basin, whereas silicate weathering played a minor role. The sodium adsorption ratio (SAR), water quality index (WQI), and sodium percentage (%Na) indicated that the groundwater in the northern sub-basin was suitable for irrigation and drinking, but that in the southern and central sub basins was not suitable. The groundwater quality was slightly better in the wet season than in the dry season. The groundwater could be used for drinking after treatment for B(3+), F(-), and SO4(2-) and for irrigation after control of the sodium and salinity hazards. Considering the high corrosivity ratio of the groundwater in this area, noncorrosive pipes should be used for the groundwater supply. For sustainable development, integrated management of the surface water and the groundwater is needed in the future. PMID- 24221558 TI - Immunogold localization of the cell-wall-matrix polysaccharides rhamnogalacturonan I and xyloglucan during cell expansion and cytokinesis inTrifolium pratense L.; implication for secretory pathways. AB - We have localized two cell-wall-matrix polysaccharides, the main pectic polysaccharide, rhamnogalacturonan I (RG-I), and the hemicellulose, xyloglucan (XG), in root-tip and leaf tissues of red clover (Trifolium pratense L.) using immunoelectron microscopy. Our micrographs show that in both leaf and root tissues RG-I is restricted to the middle lamella, with 80-90% of the label associated with the expanded regions of the middle lamella at the corner junctions between cells. Xyloglucan, however, is nearly exclusively located in the cellulose-microfibril-containing region of the cell wall. Thus, these cell wall-matrix polysaccharides are present in distinct and complementary regions of the cell wall. Our results further show that during cell expansion both RG-I and XG are present within Golgi cisternae and vesicles, thus confirming that the Golgi apparatus is the main site of synthesis of the non-cellulosic cell-wall polysaccharides. No label is seen over the endoplasmic reticulum, indicating that synthesis of these complex polysaccharides is restricted to the Golgi. The distribution of RG-I and XG in root-tip cells undergoing cell division was also examined, and it was found that while XG is present in the Golgi stacks and cell plate during cytokinesis, RG-I is virtually absent from the forming cell plate. PMID- 24221559 TI - Root contraction in hyacinth. II. Changes in tubulin levels, microtubule number and orientation associated with differential cell expansion. AB - Root contraction in hyacinth (Hyacinthus orientalis L.) is marked by reoriented cell growth in the cortex of the contractile region. Cellular volume of the inner cortex enlarges fourfold during root contraction. This is associated with large increases in the radial and tangential dimensions and decreases in the longitudinal dimension of the cells. In order to determine the possible role of microtubules (MTs) in these changes we compared tubulin levels and MT numbers and orientation in contracted and non-contracted regions of hyacinth roots. Tubulin content was analysed by a radioimmunoassay; MT numbers and orientation were analyzed by counting profiles in sectioned material using transmission electron microscopy. Contracted tissue was found to have significantly higher levels of tubulin on a per-cell basis than non-contracted tissue, and also increased tubulin levels relative to total protein. The spatial MT frequencies were the same in contracted and non-contracted tissues, indicating a proportional increase in MT numbers in the expanded cells. Although the absolute spatial frequency of MTs was constant, the orientation, as determined by morphometric analysis of MT profiles, was not. While in the longitudinal section plane 42% of the MTs in the non-contracted cells were oblique, in the contracted cells the percentage of MTs presenting oblique profiles increased to 87%. Additionally, a qualitative difference in MTs was observed in contracted cells; electron-opaque material was seen peripherally associated with the MTs of the inner cortex. The changes in tubulin levels and in MT numbers as well as the qualitative differences in the MTs of contracted and non-contracted root regions indicate that, in hyacinth, reoriented cellular enlargement associated with root contraction cannot be explained simply by shifts in the arrangement of preexisting cortical MT arrays, but involves more complex changes in the cytoskeleton. PMID- 24221560 TI - Temperature effects on malic-acid efflux from the vacuoles and on the carboxylation pathways in crassulacean-acid-metabolism plants. AB - The studies described in the paper were conducted with tissue slices of Crassulacean acid metabolism (CAM) plants floating in isotonic buffer. In a first series of experiments, temperature effects on the efflux of [(14)C]malate and(14)CO2 were studied. An increase of temperature increased the efflux from the tissue in a non-linear manner. The efflux was markedly influenced also by the temperatures applied during the pretreatment. The rates of label export in response to the temperature and the relative contributions of(14)CO2 and [(14)C]malate to the label export were different in the two studied CAM plants (Kalanchoe daigremontiana, Sempervivum montanum). In further experiments, temperature response of the labelling patterns produced by(14)CO2 fixation and light and darkness were studied. In tissue which had accumulated malate (acidified state) an increase of temperature decreased the rates of dark CO2 fixation whilst the rates of CO2 fixation in light remained largely unaffected. An increase of temperature shifted the labelling patterns from a C4-type (malate being the mainly labelled compound) into a C3-type (label in carbohydrates). No such shift in the labelling patterns could be observed in the tissue which had depleted the previously stored malate (deacidified state). The results indicate that in the acidified tissue the increase of temperature increases the efflux of malate from the vacuole by changing the properties of the tonoplast. It is assumed that the increased export of malic acid lowers the in-vivo activity of phosphoenol pyruvate carboxylase by feedback inhibition. PMID- 24221561 TI - A nuclear protein associated with cell divisions in plants. AB - A nuclear protein, present in carrot meristems and rapidly proliferating cultured cells of carrot (Daucus carota L.) has been identified by the use of a monoclonal antibody (MAb 21D7). By combining the techniques of two-dimensional polyacrylamide gel analysis and blotting separated proteins onto nitrocellulose sheets, it was shown that the antibody detected a single polypeptide of apparent molecular mass (M r) of 45000 and an isoelectric focusing point (pI) of 6.7. This protein was found by subcellular fractionation and immunofluorescence to be highly concentrated in the nucleoli of somatic and zygotic embryos of a wide range of plants. It was not detectable in logarthmically growing cells ofEscherichia coli, yeast, embryos ofDrosophila melanogaster or cultured C3H mouse cells. These data indicate that this protein is a highly conserved non histone protein associated with nuclei of rapidly dividing plant cells. PMID- 24221562 TI - Water stress and galactomannan breakdown in germinated fenugreek seeds. Stress affects the production and the activities in vivo of galactomannan-hydrolysing enzymes. AB - Imposition of water stress on germinated fenugreek (Trigonella foenum-graecum L.) seeds and isolated fenugreek endosperms after the beginning of galactomannan mobilisation caused a reduction in the rate of breakdown of the polysaccharide relative to unstressed controls. The activities, measured in vitro, of the three hydrolytic enzymes involved in the breakdown process (alpha-D-galactosidase, EC 3.2.1.22;endo-beta-D-mannanase, EC 3.2.1.78;exo-beta-D-mannanase, EC 3.2.1.25) were not decreased. Although there was some accumulation of galactomannan hydrolysis products in endosperms under stress, there was no clear correlation between sugar levels and the inhibition of galactomannan breakdown. When water stress was applied to fenugreek seeds after germination but before the beginning of galactomannan hydrolysis, both galactomannan breakdown and the development of the hydrolytic enzyme activities were inhibited. Washing of newly germinated seeds for 2 h in water prior to the imposition of stress gave partial relief of the inhibition of galactomannan mobilisation, partial recovery ofendo-beta-D mannanase levels, and full recovery of alpha-D-galactosidase levels. It is argued: 1) that water stress after germination but before the beginning of galactomannan hydrolysis inhibits the production of hydrolytic enzymes in the endosperm, probably via decreased removal at lowered water content of diffusible inhibitory substances; and 2) that water stress after the beginning of galactomannan hydrolysis decreases the rate of galactomannan breakdown in vivo principally via decreased diffusion at lowered water content of enzymes from the aleurone layer through the storage tissue of the endosperm. PMID- 24221563 TI - Mobile charges in the cell membranes ofHalicystis parvula. AB - Charge-pulse experiments were performed on cells of the giant marine algaHalicystis parvula. At normal pH (8.2), the voltage decay following a charge pulse of 500 ns duration fed to the vacuole could be described by summing two exponential relaxations. The amplitudes and time constants of these relaxations were widely separated. The parameters of the two relaxation processes were found to be pH-dependent. Reduction of the external pH value from pH 8.2 to 5 resulted in a complete change of the two relaxation processes within a few minutes. Only one relaxation process could be observed at pH 5, within the time resolution of our instrumentation. The experimental data could not be explained by a two membrane model with reasonable values for the specific capacitances of tonoplast and plasmalemma. The results of the charge-pulse relaxations were found to be consistent with the assumption that both membranes have very similar electrical properties and that both contain mobile charges with a total surface concentration of about 30 nmol.m(-2) and a translocation-rate constant of about 500.s(-1). The mobile charges became neutralized at pH 5 hhich led to a decrease of the apparent specific capacitance of the algal cells. They are presumably either part of a transport system for cations or connected with the chloride pump ofHalicystis parvula. PMID- 24221564 TI - Rapid variations in the content of the RNA of the small subunit of ribulose-1,5 bisphosphate carboxylase of mature tobacco leaves in response to localized changes in light quantity. Relationships between the activity and quantity of the enzyme. AB - Mature green leaves from tobacco (Nicotiana tabacum L.) plants were submitted to contrasting light conditions; half of each leaf was shaded (changed from 60 to 25 MUmol photons. m(-2) .s(-1)=LL) and the other half was exposed to higher light (changed from 60 to 360 MUmol.m(-2). s(-1)=HL) for 24 h. The activity and quantity of ribulose-1,5-bisphosphate carboxylase (RuBPCase) were measured during the first 24 h in each leaf region and the variation was compared with that of small subunit (SSU)-and large subunit (LSU)-mRNA contents determined by a hybridot technique. Each leaf half responded separately to the actual light received. The activity of RuBPCase increased progressively in the HL zones and decreased in the LL zones. The RuBPCase-protein content was not significantly modified during the first 24 h but SSU-mRNA content responded very rapidly to the treatment. Within 2 h a significant difference in SSU mRNA appeared between LL and HL zones: at the end of the photoperiod the content in LL zones was approx. 25% of the initial value. The increase in the exposed zone, however, was not significant, indicating that there was a dissymmetry of the response to variation in incident white light. The LSU-mRNA contents from the same leaf extracts were totally unaffected by the light treatment. No day-night variations were noted in either SSU or LSU mRNAs in control plants. PMID- 24221565 TI - Auxin causes oscillations of cytosolic free calcium and pH inZea mays coleoptiles. AB - In epidermal cells of maize (Zea mays L.) coleoptiles, cytosolic pH (pHc), cytosolic free calcium, membrane potential and changes thereof were monitored continuously and simultaneously (pHc/,psi m, Ca(2+)/psi m) using double-barrelled ion-sensitive microelectrodes. In the resting cells the cytosolic pH was 7.3-7.5 and the concentration of free calcium was 119+/-24 nM. One-micromolar indole-3 acetic acid (IAA), added to the external medium at pH 6.0 triggered oscillations inpsi m, pHc and free calcium with a period of 20 to 30 min. Acidification of the cytosolic pH increased the cytosolic free calcium. Thepsi m oscillations are attributed to changes in activity of the H(+)-extrusion pump at the plasmalemma, triggered off by DeltapH and controlled by pH regulation (pH oscillation). The origin of the pHc and Ca(2+) changes remains unclear, but is possibly caused by auxin-receptor-induced lipid breakdown and subsequent second-messenger formation. It is suggested that the observed cytosolic pH and Ca(2+) changes are intrinsically interrelated, and it is concluded that this onset of regulatory processes through the phytohormone IAA is indicative of calcium and protons mediating early auxin action in maize coleoptiles. It is further concluded that the double-barrelled ion-sensitive microelectrode is an invaluable tool for investigating in-vivo hormone action in plant tissues. PMID- 24221566 TI - Gibberellin-induced hydrolysis of endosperm cell walls in gibberellin-deficient tomato seeds prior to radicle protrusion. AB - The weakening of the mechanical restraint of the endosperm layer in tomato (Lycopersicon esculentum Mill.) seeds, a prerequisite for germination, has been studied with the use of seeds of the gibberellin (GA)-deficientgib-1 mutant. Incubation ofgib-1 endosperms, including part of the testa, in 10 MUM GA4+7, resulted within 12 h in the release of fructose, glucose, galactose and mannose into the incubation medium. Only small amounts of sugars diffused out of thegib-1 endosperms during incubation in water. Chemical hydrolysis of endosperm cell walls ofgib-1 seeds showed that they are mainly composed of mannose, and smaller quantities of glucose and galactose. Treatment with GA4+7 induced in the endosperms the production of endo-beta-mannanase activity that was not detectable during incubation in water, and also increased the activities of mannohydrolase and alpha-galactosidase as compared with the water controls. No cellulase activity was found. It is concluded that in tomato seeds the weakening of endosperms prior to radicle protrusion is mediated by a GA-induced enzymatic degradation of the mannan-rich cell walls. PMID- 24221568 TI - Phytin is synthesized in the cotyledons of germinated castor-bean seeds in response to exogenously supplied phosphate. AB - Following germination of the castor bean (Ricinus communis L.) seed, levels of phytin decline in both the endosperm and the embryo. However, as seedling growth continues, phytin increase in the latter to a level exceeding that present in the mature dry embryo, while phytin declines concomitantly in the endosperm. It is likely that phosphate mobilized from phytin in the endosperm acts as a substrate for phytin synthesis in the embryo. This is supported by the observation that isolated embryos supplied with phosphate accumulate phytin, particularly in the cotyledons. This increase is enhanced whenmyo-inositol is provided concurrently as a carbon source. Phytin synthesis in the cotyledons of the isolated embryos can occur without the attached axis. Whether initially exposed to exogenous phosphate or not, the isolated cotyledons remain competent in their ability to synthesize phytin for an extended post-germinative period, even though the major reserves are being mobilized at this time. PMID- 24221567 TI - Differential expression of nuclear- and organelle-encoded genes during tomato fruit development. AB - Steady-state mRNA levels of nuclear-and organelle-encoded genes were determined during fruit development and ripening. Transcripts specific for subunits of the mitochondrial and chloroplast ATPase complexes appear simultaneously and reach high levels two to three weeks after anthesis, but follow a different expression pattern during the ripening period. While the chloroplast-specific mRNA levels continuously decrease to low levels in ripe tomato fruits, the transcripts specific for two mitochondrial ATPase subunits continue to be present at relative high levels in red fruits. Transcript levels for the fructose-1,6-bisphosphate aldolase increase significantly during ripening. Structural proteins such as the alpha-subunit of tubulin and the hydroxyproline-rich glycoprotein extensin are expressed during maximal fruit growth. In addition, comparisons of mRNA levels of different genes in several plant organs (leaf, fruit, stem, and root) show characteristic differences. The results presented in this paper demonstrate that changes at the transcriptional or post-transcriptional level during fruit development can be correlated with morphological and physiological alterations. PMID- 24221569 TI - Preprophase bands of microtubules and the cell cycle: Kinetics and experimental uncoupling of their formation from the nuclear cycle in onion root-tip cells. AB - We have studied the timing of preprophase band (PPB) development in the division cycle of onion (Allium cepa L.) root-tip cells by combinations of immunofluorescence microscopy of microtubules, microspectrophotometry of nuclear DNA, and autoradiography of [(3)H]thymidine incorporation during pulse-chase experiments. In normally grown onion root tips, every cell with a PPB had the G2 level of nuclear DNA. Some were in interphase, prior to chromatin condensation, and some had varying degrees of chromatin condensation, up to the stage of prophase at which the PPB-prophase spindle transition occurs. In addition, autoradiography showed that PPBs can be formed in cells which have just finished their S phase, and microspectrophotometry enabled us to detect a population of cells in G2 which had no PPBs, these presumably including cells which had left the division cycle. The effects of inhibitors of DNA synthesis showed that the formation of PPBs is not fully coupled to events of the nuclear cycle. Although the mitotic index decreased 6-10-fold to less than 0.5% when roots were kept in 20 MUg.ml(-1) aphidicolin for more than 8 h, the percentage of cells containing PPBs did not decrease in proportion: the number of cells in interphase with PPBs increased while the number in prophase decreased. Almost the same phenomena were observed in the presence of 100 MUg.ml(-1) 5-aminouracil and 40 MUg.ml(-1) hydroxyurea. In controls, all cells with PPBs were in G2 or prophase, but in the presence of aphidicolin, 5-aminouracil or hydroxyurea, some of the interphase cells with PPBs were in the S phase or even in the G1 phase. We conclude that PPB formation normally occurs in G2 (in at least some cases very early in G2) and that this timing can be experimentally uncoupled from the timing of DNA duplication in the cell-division cycle. The result accords with other evidence indicating that the cytoplasmic events of cytokinesis are controlled in parallel to the nuclear cycle, rather than in an obligatorily coupled sequence. PMID- 24221570 TI - Concurrent measurements of oxygen- and carbon-dioxide exchange during lightflecks inAlocasia macrorrhiza (L.) G. Don. AB - Oxygen and CO2 exchange were measured concurrently in leaves of shade grownAlocasia macrorrhiza (L.) G. Don during lightflecks consisting of short periods of high photon flux density (PFD) superimposed on a low-PFD background illumination. Oxygen exchange was measured with a zirconium-oxide ceramic cell in an atmosphere containing 1 600 MUbar O2 and 350 MUbar CO2. Following an increase in PFD from 10 to 500 MUmol photons.m(-2).s(-1), O2 evolution immediately increased to a maximum rate that was about twice as high as the highest CO2 exchange rates that were observed. Oxygen evolution then decreased over the next 5-10 s to rates equal to the much more slowly increasing rates of CO2 uptake. When the PFD was decreased at the end of a lightfleck, O2 evolution decreased nearly instantaneously to the low-PFD rate while CO2 fixation continued at an elevated rate for about 20 s. When PFD during the lightfleck was at a level that was limiting for steady-state CO2 exchange, then the O2-evolution rate was constant during the lightfleck. This observed pattern of O2 evolution during lightflecks indicated that the maximum rate of electron transport exceeded the maximum rate of CO2 fixation in these leaves. In noninduced leaves, rates of O2 evolution for the first fraction of a second were about as high as rates in fully induced leaves, indicating that O2 evolution and the electron-transport chain are not directly affected by the leaf's induction state. Severalfold differences between induced and noninduced leaves in O2 evolution during a lightfleck were seen for lightflecks longer than a few seconds where the rate of O2 evolution appeared to be limited by the utilization of reducing power in CO2 fixation. PMID- 24221571 TI - Characteristics of 2-oxoglutarate and glutamate transport in spinach chloroplasts : Studies with a double-silicone-layer centrifugation technique and in liposomes. AB - The transport of glutamate, 2-oxoglutarate and malate in intact spinach chloroplasts was determined using a double-silicone-layer centrifugation technique in which the silicone layers stayed separated at the end of centrifugation. Glutamate was found to be transported via the dicarboxylate but not the 2-oxoglutarate translocator. Hence the kinetic parameters (i.e.K m,K i andV max) determined in glutamate-preloaded chloroplasts represent the kinetic constants of the dicarboxylate translocator. Measurements from malate- or succinate-preloaded chloroplasts represent the aggregate values of both the dicarboxylate and the 2-oxoglutarate translocators. Calculations showed that the 2-oxoglutarate and glutamate transport required to support the high fluxes of photorespiratory NH3 recycling could be achieved if the transport of these two dicarboxylates occurred on separate translocators. It is proposed that during photorespiration the transport of 2-oxoglutarate into and glutamate out of the chloroplast occurred via the 2-oxoglutarate and the dicarboxylate translocators, respectively. These transports are coupled to malate counter-exchange in a cascade-like manner resulting in a net 2-oxoglutarate/glutamate exchange with no net malate uptake. PMID- 24221572 TI - Unassembled polypeptides of the plastidic ribosomes in heat-treated 70S-ribosome deficient rye leaves. AB - The polypeptides of the subunits of 70S ribosomes isolated from rye (Secale cereale L.) leaf chloroplasts were analyzed by two-dimensional polyacrylamide gel electrophoresis. The 50S subunit contained approx. 33 polypeptides in the range of relative molecular mass (Mr) 13000-36000, the 30S subunit contained approx. 25 polypeptides in the range of Mr 13000-40500. Antisera raised against the individual isolated ribosomal subunits detected approx. 17 polypeptides of the 50S and 10 polypeptides of the 30S subunit in the immunoblotting assay. By immunoblotting with these antisera the major antigenic ribosomal polypeptides (r proteins) of the chloroplasts were clearly and specifically visualized also in separations of leaf extracts or soluble chloroplast supernatants. In extracts from rye leaves grown at 32 degrees C, a temperature which is non-permissive for 70S-ribosome formation, or in supernatants from ribosome-deficient isolated plastids, six plastidic r-proteins were visualized by immunoblotting with the anti-50S-serum and two to four plastidic r-proteins were detected by immunoblotting with the anti-30S-serum, while other r-proteins that reacted with our antisera were missing. Those plastidic r-proteins that were present in 70S ribosome-deficient leaves must represent individual unassembled ribosomal polypeptides that were synthesized on cytoplasmic 80S ribosomes. For the biogenesis of chloroplast ribosomes the mechanism of coordinate regulation appear to be less strict than those known for the biogenesis of bacterial ribosomes, thus allowing a marked accumulation of several unassembled ribosomal polypeptides of cytoplasmic origin. PMID- 24221573 TI - Hormonal regulation of gene expression in barley aleurone layers : Induction and suppression of specific genes. AB - As part of our investigation of the mode of action of plant hormones in barley (Hordeum vulgare L.) aleurone layers, we have studied the expression of five identified and three unidentified mRNA species in the presence of exogenous gibberellic acid (GA3) and abscisic acid. Three of the mRNAs are GA3-inducible, three are suppressed by GA3, and two are constitutive. The extent of the GA3 effect differs considerably for both inducible and suppressible mRNAs. For example, a ten-fold higher concentration of GA3 (10(-8) M) is required for full induction of the high-pl group alpha-amylase mRNA than is required for the low-pI alpha-amylase mRNA (10(-9) M). Temporal regulation of mRNA abundance also varies between the two alpha-amylase isoenzyme groups. The three GA3-suppressible mRNA species studied, alcohol dehydrogenase (ADH1), a probable amylase and protease inhibitor, and an unidentified barley mRNA species also varied in response to GA3. The ADH1 mRNA decreased drastically within 8 h of GA3 treatment, whereas the other two began to decrease in abundance only after 12-16 h of GA3 treatment. Abscisic-acid treatment counteracted the GA3 effects for both the inducible and suppressible mRNA species. Comparison of alpha-amylase-mRNA levels and alpha amylase-synthesis rates showed a strong correlation between the two parameters, the only exception being a lack of alpha-amylase synthesis in the presence of alpha-amylase mRNA at low GA3 concentrations. Therefore, the expression of alpha amylase seems to be regulated primarily by its mRNA levels. PMID- 24221574 TI - The biosynthesis and conjugation of indole-3-acetic acid in germinating seed and seedlings ofDalbergia dolichopetala. AB - Germinating seed ofDalbergia dolichopetala converted both [(2)H5]L-tryptophan and [(2)H5]indole-3-ethanol to [(2)H5]indole-3-acetic acid (IAA). Metabolism of [2' (14)C]IAA resulted in the production of indole-3-acetylaspartic acid (IAAsp), as well as several unidentified components, referred to as metabolites I, II, IV and V. Re-application of [(14)C]IAAsp to the germinating seed led to the accumulation of the polar, water-soluble compound, metabolite V, as the major metabolite, together with a small amount of IAA. Metabolites I, II and IV were not detected, nor were these compounds associated with the metabolism of [2'-(14)C]IAA by shoots and excised cotyledons and roots from 26-d-oldD. dolichopetala seedlings. Both shoots and cotyledons converted IAA to IAAsp and metabolite V, while IAAsp was the only metabolite detected in extracts from excised roots. The available evidence indicates that inDalbergia, and other species, IAAsp may not act as a storage product that can be hydrolysed to provide the plant with a ready supply of IAA. PMID- 24221575 TI - Determination of ethyl glucuronide in hair: a rapid sample pretreatment involving simultaneous milling and extraction. AB - A combination of simultaneous milling and extraction known as micropulverized extraction was developed for the quantification of the alcohol marker ethyl glucuronide (EtG) in hair samples using a homogeneous reference material and a mixer mill. Best extraction results from 50 mg of hair were obtained with 2-mL plastic tubes containing two steel balls (? = 5 mm), 0.5 mL of water and with an oscillating frequency of 30 s(-1) over a period of 30 min. EtG was quantified employing a validated GC-MS procedure involving derivatization with pentafluoropropionic acid anhydride. This micropulverization procedure was compared with dry milling followed by separate aqueous extraction and with aqueous extraction after manual cutting to millimeter-size snippets. Micropulverization yielded 28.0 +/- 1.70 pg/mg and was seen to be superior to manually cutting (23.0 +/- 0.83 pg/mg) and equivalent to dry grinding (27.7 +/- 1.71 pg/mg) with regard to completeness of EtG extraction. The option to process up to 20 samples simultaneously makes micropulverization especially valuable for the high throughput of urgent samples. PMID- 24221576 TI - Developing an operational model for an integrative oncology program: a qualitative descriptive feasibility study. AB - PURPOSE: We describe a descriptive qualitative study with the purpose of assessing the feasibility of developing an integrative oncology program in our region. METHODS: We conducted 39 interviews and two focus groups (n = 20) with cancer patients, their caregivers and complementary and conventional (n = 15) healthcare professionals. RESULTS: One primary theme emerged, acceptance or tolerance of an integrative oncology program, which represents concepts within four emergent categories: (1) operational model; (2) values to guide an integrative oncology program; (3) physical location and design; and (4) facilitators and barriers to establishing an integrative oncology program. CONCLUSIONS: The study was instrumental in establishing support for an integrative oncology program in our region, including a feasible model. Based in part on the results of this study, the Ottawa Integrative Cancer Centre ( www.oicc.ca ) opened in November 2011. We recommend a similar process of stakeholder engagement for others who wish to develop an integrative program in their location. PMID- 24221577 TI - A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis. AB - BACKGROUND: Few treatments have the potential to reduce the severity of radiation induced mucositis in head and neck cancer patients. Some small studies have suggested that organic honey may be a useful preventive treatment. METHODS: This investigator-initiated double-blind randomized placebo-controlled trial investigated whether honey reduced the severity of radiation-induced oral mucositis (ROM). One hundred six head and neck cancer patients from the Vancouver and Sudbury Cancer Centers in Canada were randomized to swish, hold, and swallow either 5 ml of irradiated organic manuka honey or a placebo gel, four times a day throughout radiation treatment, plus seven more days. Severity of oral mucositis according to the Radiation Therapy Oncology Group (RTOG), World Health Organization (WHO), and Oral Mucositis Assessment Scale scales, weight, and subjects' symptom severity and quality of life were assessed weekly. Sialometry was performed at baseline and at the last study visit. RESULTS: One hundred six patients were recruited. Twenty-four did not attend any mucositis assessments. One was removed from the study because of off-study consumption of store-bought manuka honey. The remaining 81 patients had at least one mucositis assessment and were included in the analysis. Sixty-two percent of subjects received concurrent chemotherapy; 81 % were male. The groups were well-matched, and blinding was excellent. Dropouts were mostly due to nausea and were similar in both arms, with 78 % being able to tolerate the study products for more than 1 week. The dropout rate was 57 % in those who received honey and 52 % in those who received placebo gel. The dropout rate in those who had concurrent chemotherapy was 59 % and in those who only received radiation was 47 %. There was no statistically significant difference between the honey and placebo arms in any of the outcome indicators. Those who completed the study in both treatment arms had low rates of RTOG greater than or equal to grade 3 mucositis; 35 % in the honey group and 43 % in the placebo group. CONCLUSION: Despite promising earlier reports, manuka honey was not tolerated well by our patients and, even when used as directed, did not have a significant impact on the severity of ROM. PMID- 24221578 TI - Expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25 (+) T regulatory cells from patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. Ets-1 transcription factor plays an important role in the suppressive activity of CD4(+)CD25(+) Treg cells and stable expression of FOXP3. To find its potential role in the pathogenesis of SLE, we investigate the mRNA expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25(+) Treg cells from patients with SLE. Real-time transcription-polymerase chain reaction analysis was used to determine the expression of Ets-1 and FOXP3 mRNA in CD4(+)CD25(+) Treg cells from 36 patients with SLE and 18 sex-and-age-matched healthy controls. The Ets-1 mRNA expression level was decreased in patients with SLE [0.225 (0.135, 0.337)] than healthy controls [0.528 (0.303, 0.681)] (P < 0.001). The expression levels of FOXP3 mRNA were lower in SLE patients [0.608 (0.272, 1.164)] than healthy controls [0.919 (0.690, 1.223)], but the difference was not significant (P = 0.106). Significant reduction in Ets-1 and FOXP3 expression was also found in new-onset SLE subgroup when compared with healthy controls (P < 0.001). The level of Ets-1 and FOXP3 mRNA was not significantly different in hyperactive and lower active SLE group when compared with inactive SLE group, respectively (P > 0.05). There were no significant differences between SLE with lupus nephritis (LN) and SLE without LN either (P > 0.05). Associations of Ets-1 and FOXP3 mRNA expression levels with major clinical and laboratory parameters of SLE patients were also analyzed. However, no significant association was found. Significant positive correlation was found between Ets-1 and FOXP3 mRNA expression in CD4(+)CD25(+) Treg cells from SLE patients (r = 0.698, P < 0.001). Our results found that the expression levels of Ets-1 mRNA were decreased in SLE patients and Ets-1 expression was positively correlated with the expression of FOXP3. It indicated that Ets-1 may play an important role in the stable expression of FOXP3 in CD4(+)CD25(+) Treg cells. PMID- 24221579 TI - Anabolic steroids affect human periodontal health and microbiota. AB - OBJECTIVES: This study aims to evaluate periodontal microbiological differences between systemically healthy nonsmoker males taking anabolic androgenic steroids (AASs) and non-AAS users and to find associations between disease severity and AAS use. METHODS: Ninety-two men practicing bodybuilding were included in the study. They were divided into AAS users and a matched control nonuser group and subgrouped based on their most severe periodontal condition. Pooled subgingival samples from each individual were cultured to evaluate specific periodontopathogen infection. RESULTS: AAS users had significantly higher prevalence of severe periodontitis. AAS users had greater gingival inflammation and clinical attachment loss of >= 3 mm than nonusers (odds ratio (OR) = 2.4; p = 0.09; 95 % confidence interval (CI) 0.8-6.4). AAS users were 4.9 times more likely to be infected with Prevotella intermedia than AAS nonusers (OR = 4.9; p = 0.003; 95 % CI 1.6-14.7). The OR of presenting subgingival Aggregatibacter actinomycetemcomitans was 8.2 times higher in AAS users (OR = 8.2; p = 0.03; 95 % CI 0.9-70.8). AAS users were 5.6 times more likely to present subgingival Candida spp. than nonusers (OR = 5.6; p = 0.02; 95 % CI 1.1-27.1). AAS users were 14.8 times more likely to present subgingival Candida parapsilosis than nonusers (OR = 14.8; p < 0.0001; 95 % CI 3.1-69.2). The likelihood of AAS users presenting subgingival Candida tropicalis was 4.3 times higher than nonusers (OR = 4.3; p = 0.03; 95 % CI 1.1-16.9). A. actinomycetemcomitans was mostly isolated in individuals with severe periodontitis and was associated with subgingival Porphyromonas gingivalis, P. intermedia, and Candida spp. CONCLUSIONS: AAS use may increase the risk for severe periodontitis and may cause a subgingival selection of certain Candida species. Specific periodontopathogens, such as Candida dubliniensis and Candida albicans, seem to be negatively affected by AAS use. The higher risk for disease progression in AAS users may be explained by the significantly higher proportions of A. actinomycetemcomitans, P. gingivalis, P. intermedia, and Candida species as compared to controls. CLINICAL SIGNIFICANCE: Data on the influence of AAS on subgingival periodontopathogens and disease progression are scarce. Higher proportions of specific periodontopathogens are plausible in AAS users. AAS users had a higher prevalence of severe periodontitis, gingival inflammation, and clinical attachment loss. Men taking AAS are at greater risk of periodontitis and specific periodontopathogen infection. PMID- 24221580 TI - TGF-betaRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis. AB - OBJECTIVES: Emdogain, containing an extract of fetal porcine enamel matrix proteins, is a potent stimulator of in vitro osteoclastogenesis. The underlying molecular mechanisms are, however, unclear. MATERIAL AND METHODS: Here, we have addressed the role of transforming growth factor-beta receptor type 1 (TGF betaRI) kinase activity on osteoclastogenesis in murine bone marrow cultures. RESULTS: Inhibition of TGF-betaRI kinase activity with SB431542 abolished the effect of Emdogain on osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand or tumor necrosis factor-alpha. SB431542 also suppressed the Emdogain-mediated increase of OSCAR, a co-stimulatory protein, and dendritic cell-specific transmembrane protein and Atp6v0d2, the latter two being involved in cell fusion. Similar to transforming growth factor-beta1 (TGF-beta), Emdogain could not compensate for the inhibition of IL-4 and IFNgamma on osteoclast formation. When using the murine macrophage cell line RAW246.7, SB431542 and the smad-3 inhibitor SIS3 blocked Emdogain-stimulated expression of the transcription factor NFATc1. CONCLUSIONS: Taken together, the data suggest that TGF-betaRI kinase activity is necessary to mediate in vitro effects of Emdogain on osteoclastogenesis. CLINICAL RELEVANCE: Based on these in vitro data, we can speculate that at least part of the clinical effects of Emdogain on osteoclastogenesis is mediated via TGF-beta signaling. PMID- 24221581 TI - Feeding repellence in Antarctic bryozoans. AB - The Antarctic sea star Odontaster validus and the amphipod Cheirimedon femoratus are important predators in benthic communities. Some bryozoans are part of the diet of the asteroid and represent both potential host biosubstrata and prey for this omnivorous lysianassid amphipod. In response to such ecological pressure, bryozoans are expected to develop strategies to deter potential predators, ranging from physical to chemical mechanisms. However, the chemical ecology of Antarctic bryozoans has been scarcely studied. In this study we evaluated the presence of defenses against predation in selected species of Antarctic bryozoans. The sympatric omnivorous consumers O. validus and C. femoratus were selected to perform feeding assays with 16 ether extracts (EE) and 16 butanol extracts (BE) obtained from 16 samples that belonged to 13 different bryozoan species. Most species (9) were active (12 EE and 1 BE) in sea star bioassays. Only 1 BE displayed repellence, indicating that repellents against the sea star are mainly lipophilic. Repellence toward C. femoratus was found in all species in different extracts (10 EE and 12 BE), suggesting that defenses against the amphipod might be both lipophilic and hydrophilic. Interspecific and intraspecific variability of bioactivity was occasionally detected, suggesting possible environmental inductive responses, symbiotic associations, and/or genetic variability. Multivariate analysis revealed similarities among species in relation to bioactivities of EE and/or BE. These findings support the hypothesis that, while in some cases alternative chemical or physical mechanisms may also provide protection, repellent compounds play an important role in Antarctic bryozoans as defenses against predators. PMID- 24221582 TI - Suppression of the powdery mildew pathogen by chitinase microinjected into barley coleoptile epidermal cells. AB - An exogenous chitinase from Streptomyces griseus was introduced into coleoptile epidermal cells of barley (Hordeum vulgare) by microinjection, and the effect of injected chitinase on the growth or development of the powdery mildew pathogen (Erysiphe graminis f. sp. hordei) was examined. Prior to microinjection, an enzymatic degradation of fungal haustorium, the organ taking nutrients from host plant cells, was examined by treating fixed coleoptile epidermis harboring haustoria with this enzyme. The result showed that haustoria were effectively digested by chitinase, suggesting the effectiveness of chitinase treatment for suppressing the fungal development. Microinjection of chitinase was conducted using living coleoptile tissues inoculated with the pathogen. Epidermal cells in which the haustorial primordia had been formed, or in which the haustoria had matured, were selected as targets for injection. The result clearly indicated that injection at the stage of primordium formation was effective in completely digesting haustoria and suppressing the subsequent formation of secondary hyphae of the pathogen. In microinjection after haustorial maturation, hyphal elongation was considerably suppressed though there was no detectable morphological change in the haustoria. Thus, the present study provides the experimental basis for genetically manipulating barley to produce transgenic plants resistant to the powdery mildew disease. PMID- 24221583 TI - The use of the polymerase chain reaction in plant transformation studies. AB - Transformed root lines of Nicotiana species, containing NPTII and Gus genes, were used to study the parameters affecting the use of the Polymerase Chain Reaction as a routine analytical tool for quickly analysing plant transformants for the presence of a foreign gene. The basic reaction mix as described by Cetus Corporation (Saiki 1989) was close to optimal for successful PCR amplification of internal sequences of both NPTII and Gus from genomic plant DNA. The temperature of primer annealing in the PCR protocols was found to be the most important variable, as low temperatures caused amplification of artefact bands and smearing after analysis on ethidium bromide agarose gels. Various formulae for calculating the Tm for binding of primers of various lengths (20-30 bases) are described in relation to predicting suitable annealing temperatures in the PCR.For tobacco species the PCR reaction worked efficiently with up to 2 MUg of genomic DNA. However, with DNA from Mentha species (mint), an inhibitor of the PCR process was co-extracted with the DNA which prevented amplification of target sequences, if more than 10 ng of genomic DNA was present in the reaction. PMID- 24221584 TI - Regulation of organogenesis and somatic embryogenesis by auxin in melon, Cucumis melo L. AB - Various tissues of seeds and seedlings of melon were cultured in vitro to study the effects of auxin concentration on organogenesis and embryogenesis. Adventitious shoots and somatic embryos were formed from explants of cotyledons of mature seeds, hypocotyls of seedlings, and leaves and petioles of young plantlets. Expanded cotyledons of seedlings formed only adventitious shoots. All tissues responded similarly to the 2,4-D concentration in the media, that is, adventitious shoots were formed at low concentration, callus proliferated without differentiation at intermediate concentration and somatic embryos were induced at high concentration. Cotyledons of mature seeds formed both adventitious shoots and somatic embryos more efficiently than any other tissues cultured.Effects of three auxins, 2,4-D, NAA and IAA, on organogenesis and embryogenesis were compared using cotyledons of mature seeds. Adventitious shoots were formed at low level of auxins (0 to 0.01 mg/l 2,4-D; 0 to 0.1 mg/l NAA; 0 to 1.0 mg/l IAA), and embryos were formed at high level of auxins (1.0 to 2.0 mg/l 2,4-D; 3.0 to 10.0 mg/l NAA; 20.0 to 100.0 mg/l IAA). IAA gave more efficient shoot formation and embryogenesis than the other auxins. PMID- 24221585 TI - Improved culture conditions for somatic embryogenesis from Asparagus officinalis L. using an aseptic ventilative filter. AB - Calli were induced from the crown of seedlings or lateral bud of young spears of Asparagus officinalis L. on Linsmaier and Skoog's (LS) solid-medium supplemented with 5 MU M 2,4-dichlorophenoxyacetic acid (2,4-D). Embryogenic callus was selected from induced calli and proliferated in LS liquid medium supplemented with 5 MU M 2,4-D. Non-vitrified somatic embryos were formed and efficiently developed into club-shaped embryos in LS hormone-free medium with 1 % gelrite in a culture vessel capped with an aseptic ventilative filter. Non-vitrified club shaped embryos developed into normal plants when transferred to half-strength LS medium without hormones, and 0.8 % agar. Carbon dioxide concentration and moisture content inside the culture vessels were measured, and their effect on embryo development is discussed. PMID- 24221586 TI - Facile transformation of Arabidopsis. AB - A protocol is described for the simple, rapid and efficient production of transgenic Arabidopsis plants. The procedure was developed using growth regulator regimes that promote adventitious embryogenesis during or immediately following Agrobacterium mediated transformation. Both the RLD and Columbia genotypes of Arabidopsis were transformed using slightly different growth regulator regimes. For the Columbia genotype two modifications of the protocol were identified which substantially improved regeneration. Cold treatment of the plants used as a source of root explants resulted in a three-fold increase in the number of morphogenic sectors produced. A more important modification was the inclusion of 25 mg/l silver nitrate (an inhibitor of ethylene action) to the medium used for shoot regeneration. This provided a ten-fold increase in the number of shoots produced. These procedures made it possible to obtain over 100 putative transformants of RLD or Columbia from a single 10 cm petri dish, within 2 or 4 weeks after exposure of root explants to the bacteria. When these were transferred to rooting media containing antibiotics, approximately 20% were able to root after kanamycin selection and 80% after hygromycin selection. All the rooted plantlets tested were shown to contain integrated donor DNA as determined by Southern blot analysis. PMID- 24221587 TI - Plantlet regeneration from cultured leaves of Cydonia oblonga L. (quince). AB - Adventitious shoots of Cydonia oblonga Quince A were obtained from leaves cultured on MS-N6 medium containing thidiazuron (TDZ) and alpha-naphthaleneacetic acid (NAA). The frequency of regeneration was high (78% of the cultured leaves with 3.2 shoots per regenerating leaf) at 32 MUM TDZ plus 0.3 MUM NAA on young leaves obtained from micropropagated shoots. Shoots were rooted by culturing them first on medium containing 5 MUM NAA for one week and then on auxinfree medium for four weeks. The regeneration protocol may be useful for selection of somaclonal variants with increased tolerance to low Fe and for transformation mediated by Agrobacterium. PMID- 24221588 TI - Callus formation and plant regeneration from somatic embryos of oat (Avena sativa L.). AB - Globular-stage somatic embryos were isolated by vortexing friable, embryogenic callus of oat (Avena sativa L.) followed by fractionation based on size. Somatic embryos were most frequently found in the 300-380 MUm size fraction. Friable, embryogenic callus was reinitiated from 55% of isolated somatic embryos. Fertile plants were regenerated from 22% of isolated somatic embryos. Reinitiation of callus from somatic embryos and growth of friable, embryogenic callus was inhibited by the selective agents G418 and methotrexate. These results suggest that somatic embryos isolated from friable, embryogenic callus of oat may be useful totipotent targets for particle acceleration-mediated transformation. PMID- 24221589 TI - Plantlets from somatic callus tissue of the woody legume Sesbania bispinosa (Jacq.) W. F. Wight. AB - In vitro regeneration of plantlets and multiplication of Sesbania bispinosa (Jacq.) W.F. Wight plants from cultured callus tissue were demonstrated. Callus was established from both cotyledons and mature leaflets on Murashige and Skoog (MS) basal medium supplemented with BAP (0.5 mg/l) and 2,4-D (2 mg/l). Callus mediated shoot bud differentiation was studied under defined nutritional, hormonal and cultural conditions. Various concentrations of BAP or kinetin (Kn) with coconut milk (CM) in MS media induced different levels of shoot bud differentiation as well as multiplication. Multiple shoot bud differentiation occurred in most of the primary calli. The best medium for shoot bud differentiation from cotyledon derived callus, contained BAP (2 mg/l) and 15% CM (V/V). More efficient shoot bud organogenesis was recorded with BAP than Kn. Supplementation with CM in MS media accelerated shoot bud organogenesis in differentiating callus tissue. Rooting of differentiated shoots was achieved by a three step culture procedure involving (a) MS solid medium containing IBA (2 mg/l), (b) growth regulator free half strength MS medium with 1% charcoal, and (c) half strength MS liquid medium free of vitamins, growth regulators and charcoal. PMID- 24221590 TI - Phenylalanine ammonia-lyase, phenolic acids and ethylene in alfalfa (Medicago sativa L.) cell cultures in relation to their embryogenic ability. AB - Phenylalanine ammonia-lyase (PAL) activity, contents of phenolic acids and ethylene production during the lag-phase, and contents of phenolic acids at the late exponential phase, showed significant differences in embryogenic (EC) and non-embryogenic (NEC) suspension cultures of Medicago sativa L. Maximum PAL activity at 6 h after inoculation was followed by an increase in the level of phenolic acids from 9.6 MUg g(-1) fresh mass to 21 MUg g(-1) fresh mass in NEC at 12 h. Thereafter the level of phenolic acids decreased to 5.2 MUg g(-1) fresh mass at 72 h. The decline was caused predominantly by the decrease of ester-bound cinnamic acid derivatives, the decrease ranging from 83 to 20% of total phenolics. Two maxima of ethylene production were observed in NEC: the first one immediately after inoculation and the second at 6 h, coinciding with the peak of PAL activity. In NEC, most of the phenolic acids occurred in esterified form. Ability to form somatic embryos (EC) was associated with the absence of the second peak of ethylene production as well as of the peak of PAL activity at 6 h. The level of phenolic acids during the lag-phase remained low (7.2 MUg g(-1) FM) and did not change. The proportion of cinnamic acid derivatives was very low (18% of total phenolics), mostly due to the extremely low level of ferulic acid. In EC, phenolic acids bound to methanol insoluble material formed the major fraction. Loss of embryogenic potential of the embryogenic culture (ECL) was associated with qualitative and quantitative changes in the contents of phenolic acids insignificantly increased PAL activity after inoculation was followed by a moderate increase in the contents of phenolic acids from 9.35 MUg g(-1) fresh mass to 12.42 MUg g fresh mass. A high rate of ethylene production was observed only immediately after the transfer of the culture to fresh medium. The loss of embryogenicity correlated also with changes in the relative amounts of the investigated fractions of phenolic acids. A distinct increase in the level of methoxy-substituted phenolic acids is a characteristic feature of the ECL culture. PMID- 24221591 TI - Detection of ginkgolide A in Ginkgo biloba cell cultures. AB - Ginkgo biloba cells were cultured in two 500 mL shake flasks and in 2 L and 6 L immobilization bioreactors using MS medium supplemented with 1 mg.L(-1) NAA, 0.1 mg.L(-1) K and 30 g.L(-1) sucrose. Specific growth rates were 0.06 d(-1), 0.11 d( 1) and 0.07 d(-1) for the 2 L and 6 L bioreactors and shake flask cultures, respectively. Extracellular phosphate, nitrate, ammonium and carbohydrate uptake rates of the bio reactor cultures were approximately 17 to 39% slower than those of shake flask cultures. The specific oxygen uptake and carbon dioxide transfer rates of immobilized Ginkgo biloba cells ranged from 0.027 to 0.041 mmol O2.g( 1).d.w.hr(-1) (maximum uptake at 14 days) and 0.020 to 0.057 mmol CO2g. ( 1).d.w.hr(-1) (maximum production at 14 days). Extracts from the biomass of the two immobilized and shake flask suspension cultures were analysed for ginkgolide A by GC-MS. Yields of 7, 17, 19 and 7 ng.g. (-1)d.w. of ginkgolide A were determined for shake flask 1, shake flask 2 and the 2 L and 6 L immobilized cultures, respectively. Traces of ginkgolide B were detected with the signal to noise ratio, however, being too low for positive confirmation of this last product. PMID- 24221592 TI - Stable transformation of sorghum cell cultures after bombardment with DNA-coated microprojectiles. AB - Cells from a suspension culture of Sorghum vulgare (sorghum) have been transformed to either hygromycin or kanamycin resistance following uptake of pBC1 or pNGI plasmids, respectively, introduced on DNA-coated high velocity microprojectiles. Hygromycin- and kanamycin-resistant transformants contained hygromycin B phosphotransferase- and neomycin phosphotransferasehybridizing restriction fragments of the expected size, respectively. A second introduced, but unselected for, reporter uidA gene which encodes beta-glucuronidase activity was also detected by DNA gel blot analysis in these transformants and shown to be expressed at low levels in two of the ten transformants analyzed. Transcripts from the introduced foreign genes accumulated to detectable levels in only these two transformants, both of which had a high copy number of genes integrated into their genome. This report further establishes the biolistic method as a useful route for delivery of DNA into the difficult-to-transform monocotyledonous plant species and represents the first stable transformation of this agronomically important cereal grain. PMID- 24221593 TI - A comparative study of somatic embryogenesis in Secale vavilovii. AB - The ability of immature embryos, inflorescences and leaves of Secale vavilovii to form embryogenic callus was tested on Murashige and Skoog (1962) medium supplemented with different concentrations of 2,4-D. All cultured immature embryos formed calluses. The highest percentage of embryogenic callus production was from 1-2 mm embryos. Young leaves also formed calluses, mainly from the 10-15 mm basal segment, the percentages of embryogenic calluses being higher when cultures were maintained in darkness. Embryogenic calluses were obtained also from all the cultured immature inflorescences, in the three cases, rooted green plants were obtained and grown in soil. Comparison of the responses of the three explants used indicates that immature inflorescence is the most useful explant for obtaining regenerated plants in Secale vavilovii. PMID- 24221594 TI - Reduced intracellular content of methotrexate in an isolated MTX-resistant cell line of Nicotiana plumbaginifolia. AB - In plant cells methotrexate (MTX) may exert its toxic effect through several mechanisms, including inhibition of its target protein dihydrofolate reductase. Resistance based on a mechanism operating before MTX binds to proteins should confer protection to plant cells. A methotrexate-resistant cell line of Nicotiana plumbaginifolia was isolated by a stepwise selection procedure. This cell line survived in the presence of 10 MUM MTX which is 50-100 fold higher than the lethal dose for the wild type cells. Neither alteration in kinetic characteristics of dihydrofolate reductase, nor elevated binding capacity of (3)H MTX to target protein(s), were observed. However, in comparison with wild type cells, markedly lower amounts of intracellular (3)H-MTX were found after the selected cell line was incubated with (3)H-MTX, indicating that either reduced uptake or enhanced efflux of MTX is the major reason for MTX-resistance in this cell line. PMID- 24221595 TI - Changes in thyroid hormone levels in eggs and larvae and in iodide uptake by eggs of coho and chinook salmon,Oncorhynchus kisutsch andO. tschawytscha. AB - Developmental profiles of thyroxin (T4), triiodothyronine (T3) and radioactive iodide uptake were established for eggs and T4 and T3 profiles were established for larvae (whole-body, yolk-only and body-only) of coho and chinook salmon. T4 and T3 were consistently present in all samples. In eggs, hormone levels remained fairly constant in all cohorst for at least the first three weeks of incubation, but then fluctuated in both directions in some sample groups. Large increases in T4 (from 9 ng/g to 245 ng/g) were seen in 1985 chinook eggs 28 days after fertilization. Radioactive iodide uptake (which was used as a possible indicator of thyroxinogenesis) increased at least 10-fold in both 1986 coho and chinook eggs from 23-30 days after fertilization. T4 (62 ng/g) and T3 (393 ng/g) were found in the bodies of 28-day-old 1986 chinook embryos. In whole larvae, hormone levels varied depending upon the cohort studied. In general, initial body-only concentrations of both T4 and T3 decreased as body weight increased, but before yolksac resorption was completed, both thyroid hormone content and concentration increased (except for chinook T3). T4 and T3 content in larval yolk stayed constant as yolksac size decreased, resulting in increased thyroid hormone concentration in the yolksac. All of these data suggest that the initial source of thyroid hormones in coho and chinook salmon eggs is maternal, but that by approximately 3-4 weeks after fertilization, the developing embryos begin to produce their own thyroid hormones. After hatching, increases in tissue T4 and T3 concentration coupled with constant T4 and T3 content in diminishing yolksacs suggest that larvae also produce their own thyroid hormones; yolksac content then may reflect both the original maternal hormones and the larva-producted hormones. PMID- 24221596 TI - The GnRH systems in the brain and pituitary of normal and hCG treated European silver eels. AB - The distribution of immunoreactive GnRH was studied in the brain and pituitary gland of normal and human chorionic gonadotrophin (hCG) injected silver eels. It was found that the general organization of GnRH systems in this species is similar to that reported in other teleosts. Cell bodies were present in the olfactory bulbs, ventral telencephalon, periventricular hypothalamus and dorsal tegmentum. No positive perikarya could be detected in the preoptic region. Only scarce fibers were observed in the proximal neurohypophysis. Treatment with hCG does not modify the distribution of GnRH but it increases the density of positive structures, in particular at the level of the pituitary. The results are discussed in relation with the present status of knowledge of the mechanisms underlying the blockage of sexual maturation in the European eel at the silver stage. PMID- 24221597 TI - Dopamine inhibits gonadotropin secretion in the Chinese loach (Paramisgurnus dabryanus). AB - The effects of dopamine on gonadotropin (GtH) secretion in sexually mature Chinese loach were investigated. Spontaneous secretion of GtH was inhibited within 1 h following an intramuscular injection of dopamine (100 MUg/g body wt). Similarly, dopamine (50 and 100 MUg/g body wt) caused a significant reduction in serum GtH in fish with elevated GtH levels as a result of pretreatment with gonadotropin-releasing hormone (GnRH) analogs either alone or in combination with the dopamine receptor antagonist domperidone. In summary, the present study provides direct evidence that dopamine functions as a gonadotropin-release inhibitory factor in the Chinese loach by blocking spontaneous and GnRH stimulated GtH release. PMID- 24221598 TI - Relativein vitro effectiveness of estradiol-17beta, androgens, corticosteroids, progesterone and other pregnene derivatives on germinal vesicle breakdown in oocytes of Indian major carps,Labeo rohita, Cirrhinus mrigala andCatla catla. AB - The relative effectiveness of estradiol-17beta, androgens, corticosteroids, progesterone and other pregnene derivatives on germinal vesicle breakdown (GVBD) was investigatedin vitro using folliculated oocytes of three carps,Labeo rohita, Cirrhinus mrigala, andCatla catla. In all three species progesterone and 17alpha hydroxyprogesterone could induce GVBD but relatively 17alpha,20beta dihydroxyprogesterone was consistently found to be the most potent maturation inducing steroid. Both estradiol-17beta and testosterone were ineffective in inducing GVBD. Androsterone and dehydroepiandrosterone were found to be effective inC. catla at all the concentrations used. Deoxycorticosterone (DOC), hydrocortisone (HC) and cortisone were effective inducer of GVBD inC. catla whereas inL. rohita andC. mrigala only cortisone was found to be effective. All 5beta-reduced pregnenes were effective in inducing GVBD inL. rohita but inC. catla, only 5beta-pregnane-17alpha-01-3,20-dione and 5beta-pregnane 3alpha,17alpha,20beta-triol and inC. mrigala, 5beta-pregnane-3alpha-ol-20- one could induce oocyte maturation. PMID- 24221599 TI - A critical analysis of gas transferin vivo and in a blood-perfused trout head preparation. AB - Gas transfer and blood acid-base status in the blood-perfused trout head preparation (in vitro) were compared with intact trout (in vivo) fitted with oral membranes, dorsal aortic, ventral aortic, and opercular cannulae. Gas transfer rates were calculated from both arterial-venous blood differences and inspired expired water differences using the Fick method. Oxygen uptake[Formula: see text] and carbon dioxide excretion[Formula: see text] were lower, while ammonia excretion[Formula: see text] was higher, in the blood-perfused head relative toin vivo rates. Gas transfer rates calculated from water were consistently greater than rates calculated from blood, the difference being greaterin vitro compared toin vivo. We conclude that the inadequacy of O2 and CO2 transfer in the blood perfused head was not due to abnormal gill diffusive conductance, but was more likely related to the reduced magnitude of the blood-to-water O2 and CO2 diffusion gradients, low hematocrit, and decreased perfusion flow rate[Formula: see text]. Under the conditions of the present study, the blood-perfused trout head is not a suitable preparation for the study of oxygen transfer. We conclude this preparation is useful for evaluating branchial carbon dioxide or ammonia transfer only when comparable measurements or manipulations cannot be made on intact fish. PMID- 24221600 TI - The innervation pattern of fast myotomal muscle in the teleostMyoxocephalus scorpius: A reappraisal. AB - The pattern of polyneuronal innervation in the sculpinMyoxocephalus scorpius was examined. The majority of fast fibres in sculpin are innervated by both adjacent nerves, and <15% receive input from sub-adjacent myotomes. Stimulation through both adjacent and sub-adjacent nerves results in muscle action potentials. Each adjacent nerve supplies 2-5 axons to a given fibre. A typical fibre is probably innervated by around 4-6 axons, and pre-terminal branching accounts for the 8-20 endplates present on these fibres. PMID- 24221601 TI - Regulation of cardiac output and gut blood flow in the sea raven,Hemitripterus americanus. AB - Coeliac artery blood flow (Fca) before and after feeding was recorded in the sea raven. To obtain basic information about the scope of cardiovascular adjustment in the sea raven, a separate series of experiments was performed, in which ventral (Pva), and dorsal (Pda) aortic blood pressure, heart rate (HR) and cardiac output (jaz) were monitored during rest and encouraged exercise.Measurements of coeliac artery flow showed that visceral blood flow is substantial, particularly after feeding, and variations in the visceral vascular conductance affect Pda directly. Simultaneous recordings of intestinal and dorsal aortic blood pressures showed no measurable difference in the two arterial pressures, refuting the idea of a vascular control at the level of the main coeliac artery. Thus, in the sea raven, the adrenergic tonus affecting the visceral vasculature presumably acts at the arteriolar level.Sea ravens encouraged to exercise increased theirjaz by 64%; 32% through HR and 25% through stroke volume. The increase injaz during encouraged exercise was sufficient to produce an elevation of both Pva and Pda, despite an increase of systemic vascular conductance, beta-adrenoceptor blockade with sotalol, however, severely impaired the increase injaz during exercise, and the change in Pda was reversed.During rest there were both an adrenergic and a cholinergic tonus affecting the HR, as revealed by the effects of injected pharmacological antagonists. Swimming activity decreased the cholinergic tonus, while the adrenergic tonus increased. PMID- 24221602 TI - Performance of the heat of the hagfish,Eptatretus cirrhatus. AB - The maximum power output of isolated perfused ventricles of the hafish (Eptatretus cirrhatus) averaged 0.367+/-0.031 mW g(-1) (n=9), considerably high than estimates for the heart of the Atlantic hagfish (Myxine glutinosa). Maximal minute volumes averaged 21.55+/-1.28 ml min(-1)kg(-1), with a mean stroke volume of 0.71+/-0.14 ml kg(-1) body weight, values which are similar to those reported for many teleost and elasmobranch hearts.Ventricular output showed the characteristic dependence upon atrial filling pressure up to an optimum filling pressure ofc. 4 mm Hg. At output pressures exceeding 14 mm Hg the stroke volume and power output fell sharply. At these afterloads, the ventral aorta remained distended following semilunar valve closure and so the volume of fluid ejected on ventricular systole was reduced. There was little change in the frequency of the heart as either input or output pressures were varied. PMID- 24221603 TI - Impact analysis of an evidence-based guideline on diagnosis of urinary tract infection in infants and young children with unexplained fever. AB - Several guidelines exist on urinary tract infection (UTI) in children. The objectives of this study were to (1) implement an evidence-based diagnostic guideline on UTI and evaluate determinants of successful implementation, and (2) determine compliance to and impact of the guideline in febrile, non-toilet trained children at the emergency department (ED). We performed a prospective cross-sectional observational study, with observations before and after implementation. Children aged 1 month to 2 years, presenting at the ED with unexplained fever (temperature above 38.5 degrees C), were included. We excluded children with a chronic underlying disease. Primary outcome measure was compliance to the standardized diagnostic strategy and determinants influencing compliance. Secondary outcome parameters included the following: number of used dipsticks, contaminated cultures, number of genuine UTI, frequency of prescribed antibiotic treatment, and hospitalization. The pre-intervention group {169 children (male 60.4 %, median age 1.0 [range 0.1-2.0])} was compared with the post-intervention group {150 children (male 54.7 %, median age 1.0 [range 0.1 1.9])}. In 42 patients (24.9 %), there was compliance to local guidelines before implementation, compared with 70 (46.7 %) after implementation (p-value < 0.001). Improvement in compliance after implementation was higher in patients 3-24 months and outside the office hours (p < 0.001). CONCLUSION: Implementation of a guideline for diagnosing UTI in febrile children at the ED has led to a significantly better compliance, especially in children aged 3-24 months. However, this study also underlines the need for a well-defined implementation strategy after launching an (inter)national guideline, taking determinants influencing implementation into account. PMID- 24221604 TI - Reply to L. Reale et al. "More and better should be done to guarantee evidence based management of ADHD in children across Europe". PMID- 24221605 TI - Characteristics of invasive pneumococcal disease in hospitalized children in Austria. AB - In a prospective surveillance study covering all pediatric wards in Austria, 308 cases of invasive pneumococcal disease (IPD) were reported in hospitalized children <5 years of age between 2002 and 2012. Incidence was 7.1 per 100,000 per year for IPD with a case fatality rate of 3 %, and 1.9 per 100,000 per year for pneumococcal meningitis with a case fatality rate of 9 %. At hospital discharge, 17 % of the children were not fully recovered and suffered from problems such as hearing or motor deficits. Persistent sequelae 6 months after hospital discharge were present in 13 % of the children, a finding that emphasizes the seriousness of IPD. From 2007 onwards, we observed a shift of pneumococcal serotypes from those covered by the heptavalent vaccine to serotypes consequently added to 10- and 13-valent vaccines, particularly regarding serotype 19A. Among antimicrobial resistances detected, macrolide resistance was predominant; however, between 2002 and 2012, we saw an overall decrease of resistance rates. CONCLUSION: Considering this change of serotypes and the high rate of permanent sequelae after IPD, our data show the importance of pediatric pneumococcal vaccination and the relevance of continuous monitoring of circulating serotypes. By the end of 2012, which was the first year of universal mass vaccination against pneumococcal disease in Austria, no change in the incidence of invasive pneumococcal disease was observed yet. PMID- 24221606 TI - Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection. AB - Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2 weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. CONCLUSION: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered. PMID- 24221607 TI - Reply to Doctor S. Ozsoylu. PMID- 24221608 TI - Vitamin D at the onset of type 1 diabetes in Italian children. AB - Low vitamin D levels have been reported in multiple immune disorders such as type 1 diabetes mellitus (T1DM). The purpose of our study was to determine vitamin D levels in children at the onset of T1DM compared with children with other diseases and to test the hypothesis that low vitamin D may increase the odds for developing diabetes. All the children (n = 58) that were consecutively admitted to our clinic at T1DM onset between May 2010 and July 2012 were compared with a control group of children (n = 166) hospitalized for other diseases, matched for sex, season of visit, and age. For each subject, we considered clinical and anthropometric data, the season at time of hospitalization, and serum 25 hydroxyvitamin D (25(OH)D), which were analyzed and compared using multivariable conditional logistic regression. Median 25(OH)D was significantly lower in the diabetic patients (36.2 nmol/l, range = 7.5-121.0 nmol/l) than in controls (48.7 nmol/l, range = 7.5-190.2 nmol/l), p = 0.010. Low 25(OH)D levels seem to increase the odds for developing T1DM (odds ratio (OR) = 3.45 for 25(OH)D 51-74 nmol/l, OR = 5.56 for 25(OH)D <= 50 nmol/l). There was no seasonal effect on the risk of developing T1DM. Median 25(OH)D level was significantly lower in patients admitted with diabetic ketoacidosis (30.2 nmol/l, range = 7.5-101.8 nmol/l) than in patients without ketoacidosis (40.7 nmol/l, range = 15.2-121.1 nmol/l), p = 0.019; but when adjusted for season, the p value was 0.116. CONCLUSIONS: Children at onset of T1DM have lower vitamin D serum levels than those with other diseases. Further longitudinal studies on children before the onset of T1DM will allow clinicians to explore the causal relationship between vitamin D and T1DM. PMID- 24221609 TI - Premature ovarian failure due to tetrasomy X in an adolescent girl. AB - Tetrasomy X associated with premature ovarian failure has been described in a few patients, and the parental origin of the extra X chromosomes has not been investigated so far in this group. A 15-year-old girl with mental retardation and minor physical anomalies showed secondary amenorrhea, high gonadotropin levels, and osteoporosis. Molecular analysis of the fibroblast cells revealed pure 48,XXXX constitution despite 48,XXXX/47,XXX mosaicism in peripheral blood. Analysis of the polymorphic markers (X22, DXYS218, DXYS267, HPRT) on the X chromosome by the quantitative fluorescent polymerase chain reaction (QF-PCR) method demonstrated that the extra X chromosomes were maternal in origin. CONCLUSION: Patients with tetrasomy X syndrome should be screened for ovarian insufficiency during early adolescence because hormone replacement therapy may be required for prevention of osteoporosis. In order to understand a potential impact of the parental origin of the extra X chromosomes on ovarian development and function, further studies are needed. PMID- 24221611 TI - Derivation of a growth rate equation describing microbial surface colonization. AB - A surface growth rate equation is derived which describes simultaneous growth and attachment during microbial surface colonization. The equation simplifies determination of attachment and growth rate, and does not require a computer program for solution. This rate equation gives the specific growth rate (MU) as a function of the number of cells on the surface (N), the incubation period (t), and the number of colonies (Ci) containing either one cell, two cells, four cells, etc, as shown below.[Formula: see text] The attachment rate (A) is given by the following relationship:[Formula: see text] The proposed colonization kinetics are compared with exponential growth kinetics using 3-dimensional computer plots. Colonization kinetics diverged most from exponential kinetics when the growth rate was low or the attachment rate was high. Using these kinetics, it is possible to isolate the effects of growth and attachment on microbial surface colonization. PMID- 24221610 TI - Attitudes towards medication use in a general population of adolescents. AB - Adolescents are becoming more independently responsible for their medication regimen; therefore, adolescence is a crucial period to address medication beliefs, as many of the beliefs may persist into adulthood and can impair adherence and willingness to continue a prescribed therapy. Within this study, we aimed to explore adolescents' general perceptions towards medicines. Adolescent students attending secondary schools in the Netherlands were invited through the school's virtual learning environment to fill in an online questionnaire. Medication beliefs were assessed using the Beliefs About Medicines Questionnaire General assessing general harm and general overuse beliefs. Within a 2-week period, 434 adolescent students responded to the questionnaire; 47.2 % thought that doctors overprescribed medication, and 20.5 % perceived medication as harmful in general. Being religious was associated with stronger harm (odds ratio (OR) 2.0, 95 % confidence interval (CI) 1.2-3.2) and overuse beliefs (OR 1.4, 95 % CI 0.9-2.1). Adolescents of native background had less concerns about overuse (OR 0.4, 95 % CI 0.2-0.8). Adolescents who actually consulted physicians had lower overuse beliefs (OR 0.6, 95 % CI 0.4-1.0). CONCLUSION: Adolescents more strongly believe in the general overuse of medicines than in general harm. Religious and ethnic background influence medication beliefs, as does previous experiences with the health-care system. Gaining more insight in adolescent patients' medication use behavior and identifying patients at risk for negative medication beliefs associated with poor adherence in clinical practice might be a first step towards a lifelong good medication use. PMID- 24221612 TI - A computer simulation of surface microcolony formation during microbial colonization. AB - Several models of microbial surface colonization have been devised to quantitate growth and attachment rates on surfaces. One of these, the surface growth rate equation, is based on the assumption that the number of microcolonies of a given size (Ci) reaches a constant value (Cmax) that is equal to the attachment rate (A) divided by the specific growth rate (MU). In this study, a computer simulation was used to determine the time required to reach Cmax. It was shown that Ci approaches Cmax asymptotically. The time required is dependent solely upon the growth rate and size of microcolonies. The number of one-celled microcolonies reaches 95% of Cmax after 4.3 generations. At low growth rates, a relatively long incubation period is required. Alternate methods that shorten the incubation time are considered. PMID- 24221613 TI - Habitat selection in two species of aquatic hyphomycetes. AB - Two species of aquatic hyphomycetes,Tetracladium marchalianum andTricladium splendens, were isolated from decaying leaves in a stream.T. marchalianum was abundant on alder leaves but absent on beech leaves, which were dominated byT. splendens. It was hypothesized that differences in some chemical key factors in the leaves would account for differences in the distribution of the 2 species. In the experiment designed to test the hypothesis, combinations of sterilized leaves and isolated fungi were used. Differences in growth of FDA active mycelium were related to differences in leaf weight loss;T. splendens decomposed beech leaves andT. marchalianum decomposed alder leaves. Extracellular protease activity corresponded with these trends but there was no detectable protein loss in the leaves. Both fungi showed a nitrogen demand, and hydrolysis of leaf proteins was complemented with absorption of free amino acids and ammonium. High concentrations of free amino acids modified the pattern for habitat selection so thatT. splendens grew substantially on alder leaves andT. marchalianum colonized beech leaves. No protease activity was, however, found fromT. marchalianum on beech leaves, and it is concluded that a more general metabolic inhibition prevents extensive growth of this species on beech leaves. The low natural abundance ofT. splendens on alder leaves, where it may grow well, may be a consequence of a specific protease inhibition and competition from other species. PMID- 24221614 TI - Effect of litter nitrogen on decomposition and microbial biomass inSpartina alterniflora. AB - The effect on decomposition of 4 different levels of nitrogen in aerial tissue ofSpartina alterniflora, collected at the end of its growing season litter, was studied in laboratory percolators for 56 days at 20?C. The CO2 evolution and the release of organic nitrogen and organic carbon were monitored. From these data, the ash-free dry weight (AFDW), nitrogen (N) content, and carbon?nitrogen (C/N) ratio were calculated at various times during decomposition. Fungal biomass, bacterial biomass, and the relative autoradiographic activity of bacteria were measured at the end of the study. Decomposition was significantly affected by the nitrogen content of the litter. A 55% increase in plant N increased overall weight loss and k by 50% and 40%, respectively. Furthermore, k (calculated from time course weight loss data) responded linearly to the 4 different levels of nitrogen inSpartina tissue. Fungi appear to dominate the microbial community. At the end of the experiment, fungal biomass was between 2.23 and 3.08% of the AFDW, and was calculated to contain 12 to 22% of the nitrogen in the litter. Bacterial biomass was 1/10 of the fungal biomass, and 12-17% of the bacteria were active. The total microbial biomass was not affected by increased plant nitrogen. In the course of decomposition, the organic nitrogen and carbon were highest in the effluent water in all treatments during the first 8 days. The respiration rate (CO2 evolution) first increased to a maximum at day 18 and then decreased to a constant rate (1-2 mg C/day/g detritus). Respiration was highest in the high N litter. The C/N ratio in all treatments increased from the start to day 8, then decreased to day 20. In low N litter, C/N then increased again as a result of increased total organic nitrogen (TON) loss relative to carbon mineralization. In the high N, this was reversed. PMID- 24221615 TI - Heterotrophic bacterial guild structure: Relationship to biodegradative populations. AB - Numerical taxonomic analysis of a freshwater bacterial guild demonstrated that the bacteria capable of growth on phenanthrene and polychlorinated biphenyl media were representative of the taxa obtained from low nutrient oligotrophic media. The diversity of heterotrophic bacteria and members of new taxa recovered from the guild followed a poisson distribution relative to the number of isolation media used. Moderately high nutrient, yeast extract peptone and glucose agar was found to be the most selective isolation medium relative to the total number of taxa recovered whereas low nutrient, lake water agar was the least selective medium used. Carbon source utilization patterns of the isolated taxa indicated that taxa within the guild had broad niche ranges and could potentially occupy many niches within a dynamic environment. The structure of the bacterial guild was dominated by mesophilic oligotrophs.The results of this investigation demonstrate that potential biodegradative populations are representative of the diverse taxa found in uncontaminated freshwater environments. PMID- 24221617 TI - Distribution ofVibrio cholerae in two Florida estuaries. AB - The distribution ofVibrio cholerae was examined in 2 Florida estuaries, Apalachicola and Tampa Bay.Vibrio cholerae serotype non-01 was the most abundant serotype, being isolated from 45% of the oyster samples, 30% of the sediments, 50% of the waters, and 75% of the blue crabs.Vibrio cholerae serotype 01 was isolated from only one oyster sample. Strong linear correlations betweenV. cholerae and temperature, salinity, or the other physical/chemical parameters measured,Escherichia coli, or fecal coliforms were not observed, but a range of temperatures and salinities appeared relevant to the distribution of the organism. The organism was present in the highest concentrations when salinities were 100/00-250/00 and temperatures were 20?C-35?C.In vitro growth curves of 95V. cholerae environmental isolates further supported that 100/00-250/00 was an ideal salinity range for the organisms. The results suggest thatV. cholerae is a widely distributed organism in the nutrient-rich warm waters of the Gulf Coast estuaries. PMID- 24221616 TI - Electron microscope study of the interaction of epibiontic bacteria withChromatium minus in natural habitats. AB - Epibiontic cells on the surface of the photosynthetic purple sulfur bacteriumChromatium minus, collected several times during the year from 3 different Spanish lakes, were examined using scanning and transmission electron microscopy. The cells attached to theC. minus cell wall by an electron-dense pad, but did not enter the cell. They were ovoidal (about 0.6MUm wide) when free, and slightly curved rods (0.3*0.6MUm) when undergoing division. Division only occurred when cells remained attached toChromatium. A septum was formed, resulting in 2 or 3 curved rods surrounded by a common capsule. Detached daughter cells became ovoidal.The host ultrastructure changed as a result of epibiontic attachment, showing symptoms of cellular degradation. Simultaneously, plaques could be detected on cell lawns formed spontaneously upon cell sedimentation from field samples. PMID- 24221618 TI - [Transfusion management in gastrointestinal hemorrhage]. PMID- 24221619 TI - [The gastroenterology intensive care patient-a special problem patient?]. PMID- 24221620 TI - [Psychopharmacotherapy in emergency medicine]. AB - Part two of the CME article Psychotropic agents and psychopharmacotherapy in emergency medicine aims to give an understanding of the pharmacotherapy of psychiatric disorders in emergency medicine. In contrast to somatic emergencies, many emergency physicians are not familiar with the treatment of psychiatric emergencies, although there are guidelines and recommendations. In the following article, treatment recommendations for the 5 most common and relevant syndromes in emergency medicine (i.e., suicide, delirium, agitation, stupor, and syndromes due to psychopharmaceutical use) are described based on the German S2-Guideline Emergency Psychiatry that will be published soon. PMID- 24221622 TI - Photoassimilate-transport characteristics of nonchlorophyllous and green tissue in variegated leaves of Coleus blumei Benth. AB - The nonchlorophyllous (albino) tissue of mature C. blumei leaves is a sink for photoassimilate. Transport from the green to the albino region of the same leaf was inhibited by cold and anoxia. When the green tissue of mature leaves was removed, the remaining albino portion imported labeled translocate from other mature leaves in the phloem. Photoassimilate unloading in the albino region of mature leaves was studied by quantitative autoradiography. The unloading was inhibited by cold but not by anoxia. No labeled photoassimilate could be detected in the free space of mature albino tissue by compartmental efflux analysis as phloem unloading proceeded in a N2 atmosphere, indicating that unloading, may occur by a symplastic pathway as it apparently does in sink leaves of other species. The minor veins of mature albino leaf tissue did not accumulate exogenous [(14)C]sucrose. Minor veins of green tissue in the same leaves accumulated [(14)C]sucrose but, in contrast to other species studied to date, this accumulation was insensitive to the inhibitor p-chloromercuribenzensulfonic acid (PCMBS).In its capacity to import and unload photoassimilate, and in the inability, of the minor veins to accumulate exogenous sucrose, the albino region of the mature C. blumei lamina differs from mature albino tobacco leaves and darkened mature leaves of other species. This, together with evidence indicating that phloem loading in C. blumei and other species may occur by different routes and with different sensitivity to PCMBS, indicates that the mechanism of transfer of photoassimilates between veins and surrounding tissues, and the mechanism of the sink-source transition, may not be the same in the leaves of all species. It is speculated that the unusual properties of the C. blumei leaf may be a consequence of the presence, in the minor veins, of "intermediary cells", large companion cells connected to the bundle sheath by abundant plasmodesmata. PMID- 24221623 TI - Development of maize plants from cultured shoot apices. AB - Excised shoot apices of maize (Zea mays L.), comprising the apical meristem and one or two leaf primordia, have been cultured and can form rooted plantlets. The plantlets, derived from meristems that had previously formed 7-10 nodes, develop into mature, morphologically normal plants with as many nodes as seed-grown plants. These culture-derived plants exhibited the normal pattern of development, with regard to the progression of leaf lengths along the plant and position of axillary buds and aar shoots. Isolation of the meristem from previously formed nodes reinitiates the pattern and number of nodes formed in the new plant. Thus, cells of the meristem of a maize plant at the seedling stage are not determined to form a limited number of nodes. PMID- 24221624 TI - Cell-lineage patterns in the shoot apical meristem of the germinating maize embryo. AB - A fate map for the shoot apical meristem of Zea mays L. at the time of germination was constructed by examining somatic sectors (clones) induced by gamma-rays. The shoot apical meristem produced stem, leaves, and reproductive structures above leaf 6 after germination and the analysis here concerns their formation. On 160 adult plants which had produced 17 or 18 leaves, 277 anthocyanin-deficient sectors were scored for size and position. Sectors found on the ear shoot or in the tassel most often extended into the vegetative part of the plant. Sectors ranged from one to six internodes in length and some sectors of more than one internode were observed at all positions on the plant. Single internode sectors predominated in the basal internodes (7,8,9) while longer sectors were common in the middle and upper internodes. The apparent number of cells which gave rise to a particular internode was variable and sectors were not restricted to the lineage unit: a leaf, the internode below it, and the axillary bud and prophyll at the base of the internode. These observations established two major features of meristem activity: 1) at the time of germination the developmental fate of any cell or group of cells was not fixed, and 2) at the time of germination cells at the same location in a meristem could produce greatly different amounts of tissue in the adult plant. Consequently, the developmental fate of specific cells in the germinating meristem could only be assigned in a general way. PMID- 24221625 TI - Induction by antimycin A of cyanide-resistant respiration in heterotrophic Euglena gracilis: Effects of growth, respiration and protein biosynthesis. AB - The addition of antimycin A during the logarithmic phase of growth of heterotrophic Euglena gracilis cultures (in lactate or glucose medium) was immediately followed by decreased respiration and a cessation of grwoth. Induced cyanideresistent respiration appeared 5 h after the addition of the inhibitor then the cells started to grow again and could be cultured in the presence of antimycin A. Thus the cells exhibited a cyanide-and antimycin-resistant respiration which was, in addition, sensitive to salicylhydroxamic acid and propylgallate. Antimycin-adapted Euglena and control cells were compared for their biomass production and protein synthesis. The difference in growth yield between control and antimycin-adapted cells was not as high as would be expected if only the first phosphorylation site of the normal respiratory chain was active in the presence of antimycin A. Furthermore, the ability to incorporate labelled valine into proteins, under resting-cell conditions, was not changed. Strong correlations were established between the effects of respiratory effectors on O2 consumption and valine incorporation. These results suggest that sufficient energy for protein synthesis and growth is provided by the operation of the cyanide-resistant respiratory pathway in antimycin-adapted Euglena. PMID- 24221626 TI - Starch synthesis by isolated amyloplasts from wheat endosperm. AB - The aim of this work was to discover which compound(s) cross the amyloplast envelope to supply the carbon for starch synthesis in grains of Triticum aestivum L. Amyloplasts were isolated, on a continuous gradient of Nycodenz, from lysates of protoplasts of endosperm of developing grains, and then incubated in solutions of (14)C-labelled: glucose, glucose 1-phosphate, glucose 6-phosphate, fructose 6 phosphate, fructose-1,6-bisphosphate, dihydroxyacetone phosphate and glycerol 3 phosphate. Only glucose 1-phosphate gave appreciable labelling of starch that was dependent upon the integrity of the amyloplasts. Incorporation into starch was linear with respect to time for 2 h. At the end of the incubations, 98% of the (14)C in the soluble fraction of the incubation mixture was recovered as [(14)C]glucose 1-phosphate. Thus it is unlikely that the added [(14)C glucose 1 phosphate was extensively metabolized prior to uptake by the amyloplasts. It is argued that the behaviour of the isolated amyloplasts, and previously published data on the labelling of starch by [(13)C]glucose, are consistent with the view that in wheat grains it is a C-6, not a C-3, compound that enters the amyloplast to provide the carbon for starch synthesis. PMID- 24221627 TI - Storage of the phytochrome-mediated phototropic stimulus of moss protonemal tip cells. AB - A phytochrome-regulated phototropic response of the moss Ceratodon purpureus was investigated. Chlorotetracycline (CTC) was used to visualize membrane-associated calcium gradients in the tip cell of moss caulonemal filaments. A tip-to-base Ca(2+) gradient was observed. The ionophore monensin rapidly inhibited the growth of the tip cell and abolished the CTC fluorescence. Six hours after transferring to inhibitor-free medium, protonemal growth resumed and reached the normal growth rate within 12 h. The growth was accompanied by a reappearance of the CTC fluorescence gradient. Unilateral irradiation given during the monensin treatment or after the treatment during the period when growth inhibition persisted led, with the re-initiation of growth, to a typical positive phototropic bending in complete darkness. Far-red light applied just before the growth response started, or during growth inhibition, abolished the phototropic response. The phytochrome mediated signal was qualitatively (position) and quantitatively (degree of bending) memorized. Signal perception and response could be separated temporally. This result indicates that at least under some circumstances, e.g. under the influence of monensin, the phytochrome-mediated signal can be stored for several hours in darkness. Calcium seems to be essential for the processing of polar growth only. A specific function (second messenger) in phytochrome-dependent signal transduction could not be confirmed. PMID- 24221628 TI - Chloroplast messenger RNAs of free and thylakoid-bound polysomes from Vicia faba L. AB - Purified chloroplasts from developing leaves of Vicia faba L. were broken and separated into stroma and thylakoid fractions. Both fractions contained polysomes as demonstrated by analytical density gradient centrifugation and in-vitro read out translation. Messenger RNAs of free and thylakoid-bound polysomes were isolated and analysed by hybridization with heterologous gene probes from spinach and tobacco. Transcripts of the chloroplast genes psaA, psbB, psbC, psbD and petA were found predominantly on thylakoidbound polysomes engaged in the synthesis and the contrasslational integration of membrane proteins. In contrast, transcripts of the genes rbcL, psbE, petD, atpA, atpB, atpE and atpH were found more frequently on free polysomes corresponding to a stroma-located translation of these mRNAs and a posttranslational integration of the encoded intrinsic membrane proteins. We conclude from these findings that chloroplast-encoded membrane proteins are integrated by co-and posttranslational mechanisms. PMID- 24221629 TI - A membrane-bound enzyme complex synthesising glucan and glucomannan in pine tissues. AB - Particulate membrane preparations isolated from cambial cells and differentiating and differentiated xylem cells of pine (Pinus sylvestris L.) trees synthesised [(14)C]glucans using either guanosine 5'-diphosphate (GDP)-D-[U-(14)C]glucose or uridine 5'-diphosphate (UDP)-D-[U-(14)C]glucose as glycosyl donors. Although these glucans had beta-(1->3) and beta-(1->4) linkages in an approximate ratio 1:1, the distribution of the linkages in the glucan synthesised from GDP-D glucose was different from that synthesised from UDP-D-glucose. The synthesis of the mixed beta-(1->3) and beta-(1->4) glucan from GDP-D-[U-(14)C]glucose was changed to that of beta-(1->4) glucomannan in the presence of increasing concentrations of GDP-D-mannose. The glucan formed from UDP-D-[U-(14)C]glucose was not affected by any concentration of GDP-D-mannose. The membrane preparations epimerized GDP-D-glucose to GDP-D-mannose; however, the low amount of GDP-D mannose formed was not incorporated into the polymer becaus the affinity of the synthase for GDP-D-glucose was much greater than that for GDP-D-mannose. The glucan formed from GDP-D-glucose and the glucomannan formed from GDP-D-glucose together with GDP-D-mannose were characterized. The apparent K m and V max of the glucan synthase for GDP-D-glucose were 6.38 MUM and 5.08 MUM.min(-1), respectively. No lipid intermediates were detected during the synthesis of either glucan or glucomannan. The results indicated that an enzyme complex for the formation of the glucomannan was bound to the membrane. PMID- 24221630 TI - Initiation of morphogenic cell-suspension and protoplast cultures of barley (Hordeum vulgare L.). AB - Cell-suspension cultures were initiated from embryogenic calli of various barley cultivars. Seven fast-growing suspension lines were obtained from four different cultivars (cvs. Dissa, Emir, Golden Promise and Igri). Two of these cell suspensions showed morphogenic capacity. From a cell suspension of cv. Dissa, albino plantlets were regenerated when aggregates were cultured on solid medium. Aggregates of cv. Igri usually stopped differentiation at the globular stage, but occasionally formed scutellum-like structures. Five suspension lines were used for protoplast isolation and culture. Dividing protoplasts were obtained from all lines, but with cv. Igri a few divisions only and no further development were observed. Protoplasts from the various lines differed in the time of first division (2-14 d), division frequency (0.09-70.9%) and efficiency of colony formation (0.09-7.3%). Protoplasts isolated from the morphogenic cell suspension of cv. Dissa developed compact calli which sporadically regenerated albino plantlets. PMID- 24221631 TI - Metabolic links between the biosynthesis of pyrrolizidine alkaloids and polyamines in root cultures of Senecio vulgaris. AB - Isotope feeding and inhibitor experiments were performed in order to elucidate the pathway common to polyamine and alkaloid biosynthesis in root cultures of Senecio vulgaris L. alpha-Difluoromethylarginine, a specific inhibitor of arginine decarboxylase, prevented completely the incorporation of radioactivity from [(14)C]arginine and [(14)C]ornithine into spermidine and the pyrrolizidine alkaloid senecionine N-oxide. In contrast, alpha-difluoromethylornithine, a specific ornithine-decarboxylase inhibitor, had no effect on the flow of radioactivity from labelled ornithine and arginine into polyamines and alkaloids. Thus, putrescine, the common precursor of polyamines and pyrrolizidine alkaloids, is exclusively derived via the arginine-agmatine route. Ornithine is rapidly transformed into arginine. Recycling of the guanido moiety of agmatine back to ornithine can be excluded. Putrescine and spermidine were found to be reversibly interconvertable and to excist in a highly dynamic state. In contrast, senecionine N-oxide did not show any turnover but accumulated as a stable metabolic product. In-vivo evidence is presented that the carbon flow from arginine into the polyamine/alkaloid pathway may be controlled by spermidine. The possible importance of the metabolic coupling of pyrrolizidine-alkaloid biosynthesis to polyamine metabolism is discussed. PMID- 24221632 TI - beta-Oxidation of fatty acids in algae: Localization of thiolase and acyl-CoA oxidizing enzymes in three different organisms. AB - In the algae Mougeotia, Bumilleriopsis and Eremosphaera, recently shown to possess the enzymes hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) and enoyl-CoA hydratase (EC 4.2.1.17), the presence of thiolase (EC 2.3.1.9) and acyl-CoA oxidizing enzymes can also be demonstrated, indicating that beta-oxidation of fatty acids is possible in these organisms. The compartmentation of enzymes is different in the various algae. In Mougeotia, both thiolase and the acyl-CoA oxidizing enzyme are located exclusively in the peroxisomes. The latter enzyme was found to be an oxidase using molecular oxygen as an electron acceptor. On the other hand, in Bumilleriopsis all enzymes of the fatty-acid beta-oxidation pathway tested are constituents only of the mitochondria, and acyl-CoA is oxidized by a dehydrogenase incapable of reducing oxygen. Finally, in Eremosphaera thiolase and acyl-CoA-oxidizing enzymes were found in the peroxisomes as well as in the mitochondria. In the peroxisomes, oxidation of acyl CoA is catalyzed by an oxidase, whereas the corresponding enzyme in the mitochondria is a dehydrogenase. The acyl-CoA oxidases/dehydrogenases of the three algae differ not only by their capability for oxidation of acyl-CoA of different chain lengths but also with regard to their Km values and substrate specificities. Indications were obtained that the oxygen is reduced to water rather than to H2O2 by the algal acyl-CoA oxidases. When cells of Eremosphaera were cultured with hypolipodemic substances in the growth medium the activities of the peroxisomal enzymes, but not those of the mitochondrial enzymes of the fatty-acid beta-oxidation pathway, were increased by a factor of two to three. PMID- 24221633 TI - Regulation of glutathione S-transferases of Zea mays in plants and cell cultures. AB - An antiserum to glutathione S-transferase (EC 2.5.1.18) from maize (Zea mays L.) responsible for herbicide detoxification has been raised in rabbit. The antiserum was specific to the Mr 26000 subunit of the enzyme from maize seedlings and suspension-cultured cells, and recognized the isoenzymes active toward both atrazine and metolachlor. When plants were treated for 24 h with the herbicide antidote N,N-diallyl-2-2-dich-loroacetamide (DDCA), enzyme activities toward metolachlor were doubled in the roots and this was associated with a 70% increase in immunodetectable protein. Translation of polysomal RNA in vitro showed that the increase in the transferase in root tissue was brought about by a ninefold increase in mRNA activity encoding the enzyme. Treatment of suspension-cultured cells with cinnamic acid, metolachlor and DDCA raised enzyme activities but did not increase synthesis of glutathione S-transferase. In cultured maize cells, enzyme synthesis was maximal in mid-logarithmic phase, coinciding with the highest levels of enzyme activity. When callus cultures were established from the shoots of a maize line known to conjugate chloro-s-triazines, enzyme activity towards atrazine was lost during primary dedifferentiation. However, levels of total immunodetectable enzyme and activity toward metolachlor were increased in cultured cells compared with the parent shoot tissue. PMID- 24221634 TI - Slender barley: A constitutive gibberellin-response mutant. AB - In barley (Hordeum vulgare L. cv. Herta), slender (sln1) is a single-locus recessive mutation which causes a plant to appear as if it had been grown in sturating concentrations of gibberellin (GA). We have investigated two of the GA mediated processes in slender barley, shoot elongation and the induction of hydrolytic enzymes in aleurone layers. Shoot elongation is severely retarded in normal (wild-type) barley if the biosynthesis of GA is blocked by an inhibitor, ancymidol (alpha-cyclopropyl-alpha-(p-methoxyphenyl)-5-pyrimidinemethanol). However, the slender mutant continues to elongate in the presence of ancymidol. In isolated normal aleurone layers, the synthesis and secretion of alpha-amylase (EC 3.2.1.1), protease (EC 3.4) and nuclease (EC 3.1.30.2) are induced by exogenously applied GA3. However, in the aleurone layers of the slender mutant these enzymes are produced even in the absence of GA but their synthesis is still susceptible to inhibition by abscisic acid. Bioassays of half-seeds of the slender mutant and their normal siblings show no detectable differences in endogenous levels of GA-like substances. We suggest that the slender mutation allows competent tissues to express fully, or over-express, appropriate GA induced processes independent of GA. We also conclude that shoot elongation, and hydrolytic-enzyme secretion in aleurone layers, share a common regulatory element. PMID- 24221635 TI - Hormonal regulation of gene expression in the "slender" mutant of barley (Hordeum vulgare L.). AB - The "slender" mutant of barley resembles a normal barley plant treated with high doses of gibberellic acid (GA3). Expression of GA3-regulated and abscisic acid (ABA)-regulated mRNAs was studied in the endosperm and roots of mutant and wild type (WT) plants.Production of alpha-amylase (EC 3.2.1.1) by WT embryoless half grains was dependent on the presence of GA3, and was prevented by ABA. In contrast, alpha-amylase was produced by half-grains of the slender mutant in the absence of added GA3, although it was still reduced by ABA. The spectrum of alpha amylase mRNAs in "slender" embryoless half-grains incubated in the absence of added GA3 was the same as in WT endosperm half-grains incubated in the presence of GA3. These results indicate that the endosperm of the slender mutant exhibits similar properties to WT endosperm treated with GA3.In roots the expression of an ABA-inducible mRNA was similar in slender and WT seedlings either treated with exogenous ABA or exposed to dehydration. This result, and the effect of ABA on alpha-amylase production by the endosperm, indicate that the slender plants retain sensitivity to ABA. PMID- 24221636 TI - Estimating position-time relationships in steady-state, one-dimensional growth zones. AB - Two methods are described for estimating position-time relationships (pathlines) in steady, one-dimensional growth zones. Pathlines can be used to provide a time base for spatial data in developmental studies. The methods apply within extension-only zones (zones of growth without cell division) and require data for cell-number densities, or cumulative cell numbers, or mean cell lengths, and for the overall elongation rate of an organ. The first method ("continuous-pathline" method) can be used to estimate spatial velocity fields within extension-only zones and pathlines can then be obtained by integration of the velocity data. This method is based on the continuity equation for cell-number densities. Pathlines can also be estimated using a simple graphical version of this method. The second method ("pathline-coordinate" method) is based on the approximation that a cell of mean length remains of mean length as it moves through the extension-only zone, and can be used to estimate the coordinates of wall pathlines at discrete intervals. The methods are illustrated using published data from studies of apical growth in Zea mays L. roots and of intercalary growth in Triticum aestivum L. leaves. PMID- 24221637 TI - Action of light, nitrate and ammonium on the levels of NADH- and ferredoxin dependent glutamate synthases in the cotyledons of mustard seedlings. AB - In mustard (Sinapis alba L.) cotyledons, NADH-dependent glutamate synthase (NADH GOGAT, EC 1.4.1.14) is only detectable during early seedling development with a peak of enzyme activity occurring between 2 and 2.5 d after sowing. With the beginning of plastidogenesis at approximately 2 d after sowing, ferredoxindependent glutamate synthase (Fd-GOGAT, EC 1.4.7.1) appears while NADH GOGAT drops to a very low level. The enzymes were separated by anion exchange chromatography. Both enzymes are stimulated by light operating through phytochrome. However, the extent of induction is much higher in the case of Fd GOGAT than in the case of NADH-GOGAT. Moreover, NADH-GOGAT is inducible predominantly by red light pulses, while the light induction of Fd-GOGAT operates predominantly via the high irradiance response of phytochrome. The NADH-GOGAT level is strongly increased if mustard seedlings are grown in the presence of nitrate (15 mM KNO3,15 mM NH4NO3) while the Fd-GOGAT level is only slightly affected by these treatments. No effect on NADH-GOGAT level was observed by growing the seedlings in the presence of ammonium (15 mM NH4Cl) instead of water, whereas the level of Fd-GOGAT was considerably reduced when seedlings were grown in the presence of NH4Cl. Inducibility of NADH-GOGAT by treatment with red light pulses or by transferring water-grown seedlings to NO 3 (-) -containing medium follows a temporal pattern of competence. The very low Fd-GOGAT level in mustard seedlings grown under red light in the presence of the herbicide Norflurazon, which leads to photooxidative destruction of the plastids, indicates that the enzyme is located in the plastids. The NADH-GOGAT level is, in contrast, completely independent of plastid integrity which indicates that its location is cytosolic. It is concluded that NADH-GOGAT in the early seedling development is mainly concerned with metabolizing stored glutamine whereas Fd-GOGAT is involved in ammonium assimilation. PMID- 24221640 TI - Preparation and characterization of conductive and transparent ruthenium dioxide sol-gel films. AB - RuO2 conductive thin films were synthesized using the sol-gel method and deposited onto transparent insulating substrates. The optical transmission, film thickness, surface morphology and composition, resistivity, and spectroelectrochemical performance have been characterized. The optical transmission values of these films ranged from 70 to 89% in the visible region and from 56 to 88% in the infrared region. Resistivity values of the RuO2 sol-gel films varied from 1.02 * 10(-3) to 1.13 Omega cm and are highly dependent on the initial solution concentration of RuO2 in the sol-gel. The RuO2 sol-gel films were used as electrodes for the electrochemical oxidation and reduction of ferrocenemethanol. The electrochemical behavior of our novel RuO2 sol-gel films was compared to that of a standard platinum disk electrode and showed no appreciable differences in the half-wave potential (E1/2). The mechanical and chemical stability of the coatings was tested by physical abrasion and exposure to highly acidic, oxidizing Piranha solution. Repeated exposure to these extreme conditions did not result in any appreciable decline in electrochemical performance. Finally, the use of the novel RuO2 sol-gel conductive and transparent films was demonstrated in a spectroelectrochemistry experiment in which the oxidation and reduction of ferrocenemethanol was monitored via UV-vis spectroscopy as the applied potential was cycled. PMID- 24221639 TI - Two rapidly evolving genes contribute to male fitness in Drosophila. AB - Purifying selection often results in conservation of gene sequence and function. The most functionally conserved genes are also thought to be among the most biologically essential. These observations have led to the use of sequence conservation as a proxy for functional conservation. Here we describe two genes that are exceptions to this pattern. We show that lack of sequence conservation among orthologs of CG15460 and CG15323-herein named jean-baptiste (jb) and karr, respectively-does not necessarily predict lack of functional conservation. These two Drosophila melanogaster genes are among the most rapidly evolving protein coding genes in this species, being nearly as diverged from their D. yakuba orthologs as random sequences are. jb and karr are both expressed at an elevated level in larval males and adult testes, but they are not accessory gland proteins and their loss does not affect male fertility. Instead, knockdown of these genes in D. melanogaster via RNA interference caused male-biased viability defects. These viability effects occur prior to the third instar for jb and during late pupation for karr. We show that putative orthologs to jb and karr are also expressed strongly in the testes of other Drosophila species and have similar gene structure across species despite low levels of sequence conservation. While standard molecular evolution tests could not reject neutrality, other data hint at a role for natural selection. Together these data provide a clear case where a lack of sequence conservation does not imply a lack of conservation of expression or function. PMID- 24221641 TI - Assessment of cardiac safety during fingolimod treatment initiation in a real world relapsing multiple sclerosis population: a phase 3b, open-label study. AB - The aim of this study was to evaluate short-term safety and tolerability of fingolimod in a real-world population with relapsing multiple sclerosis, focusing on cardiac safety during treatment initiation. Patients received fingolimod 0.5 mg once daily for four months. Patients excluded from the pivotal studies with certain pre-existing cardiac conditions or baseline cardiac findings (PCCs), and those receiving beta blockers (BBs) and/or calcium channel blockers (CCBs), were eligible. Heart rate (HR) and electrical conduction events were monitored using ambulatory electrocardiography for at least 6 h after the first dose. Of 2,417 enrolled patients, 2,282 (94.4 %) completed the study. Fingolimod initiation was associated with a transient, mostly asymptomatic decrease in HR. Bradycardia adverse events occurred in 0.6 % of patients and were more frequent in individuals receiving BBs/CCBs (3.3 %) than in other patient subgroups (0.5-1.4 %); most events were asymptomatic, and all patients recovered without pharmacological intervention. In the 6 h post-dose, the incidences of Mobitz type I second-degree atrioventricular block (AVB) and 2:1 AVB were higher in patients with PCCs (4.1 and 2.0 %, respectively) than in those without (0.9 and 0.3 %, respectively); at pre-dose screening, patients with PCCs had the same incidence of Mobitz type I second-degree AVB (4.1 %) and a slightly lower incidence of 2:1 AVB (0.7 %) than 6 h post-dose. All recorded conduction abnormalities were asymptomatic. This study adds to the evidence showing that cardiac effects during fingolimod initiation remain consistent with those known from previous, controlled studies, even if patients with PCCs are included. PMID- 24221642 TI - Pharmacological therapies in post stroke recovery: recommendations for future clinical trials. AB - Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. PMID- 24221643 TI - Enhanced reticulospinal output in patients with (REEP1) hereditary spastic paraplegia type 31. PMID- 24221644 TI - Ischemic stroke as clinical onset of POEMS syndrome. PMID- 24221645 TI - Prevalence of cortical superficial siderosis in patients with cognitive impairment. AB - Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group. PMID- 24221647 TI - Environmental regulation of H2 utilization ( (3)H 2 exchange) among natural and laboratory populations of N2 and non-N 2 fixing phytoplankton. AB - Regulation of H2 utilization, as monitored by the hydrogenase-mediated(3)H2 exchange reaction, was examined among phytoplankton communitiesin situ and populations in culture. During a 2-year study in the Chowan River, North Carolina, at least 2 major groups of phytoplankton dominated(3)H2 exchange rates. They included N2 fixing cyanobacteria and NO3 (})- utilizing genera. Utilization of(3)H2 by N2 fixers was mainly dark-mediated, whereas(3)H2 utilization associated with periods of NO3 (})- abundance revealed an increasing dependence on light. Inhibitors of N2 fixation (C2H2 and NH4 (+)) negatively affected(3)H2 utilization, substantiating previous findings that close metabolic coupling of both processes exists among N2 fixing cyanobacteria. Conversely, NO3 (})- stimulated(3)H2 utilization among N2 and non-N2 fixing genera, particularly under illuminated conditions. A variety of environmental factors were shown to control(3)H2 exchange. In addition to the nitrogen sources discussed above, dissolved O2, photosynthetically available radiation (PAR), temperature, and pH changes altered(3)H2 exchange rates. It is likely that other factors not addressed here could also affect(3)H2 exchange rates. At least 2 ecological benefits from H2 utilization in natural phytoplankton can be offered. They include the simultaneous generation of adenosine triphosphate (ATP) and consumption of O2 during the oxidation of H2 via an oxyhydrogen or "Knallgas" reaction. Both processes could help sustain phytoplankton, and particularly cyanobacterial, bloom intensity under natural conditions when O2 supersaturation is common in surface waters. H2 utilization appeared to be a general feature of natural and laboratory phytoplankton populations. The magnitudes of(3)H2 utilization rates were directly related to community biomass. Although it can be shown that utilization rates are controlled by specific environmental factors, the potential relationships between H2 utilization and phytoplankton primary production remain poorly understood. PMID- 24221648 TI - Respiration rates in heterotrophic, free-living protozoa. AB - Published estimates of protozoan respiratory rates are reviewed with the object of clarifying their value in ecological studies. The data show a surprisingly large variance when similarly sized cells or individual species are compared. This is attributed to the range of physiological states in the cells concerned. The concept of basal metabolism has little meaning in protozoa. During balanced growth, energy metabolism is nearly linearly proportional to the growth rate constant; at the initiation of starvation, metabolic rate rapidly declines. Motility requires an insignificant fraction of the energy budget of protozoans. For growing cells, metabolic rate is approximately proportional to weight(0.75) and the data fall nearly exactly on a curve extrapolated from that describing the respiration rates of poikilotherm metazoans as a function of body weight. It is conceivable that protozoan species exist with lower maximum potential growth and metabolic rates than those predicted from cell volume and the equations derived from the available data. However, the lack of information concerning the state of the cells studied prevents verification of this idea. Laboratory measurements of protozoan respiratory rates have no predictive value for protozoa in nature other than delimiting a potential range. For small protozoans, this range may, on an individual basis, represent a factor of 50. PMID- 24221649 TI - Chlorophylla and adenosine triphosphate levels in Antarctic and temperate lake sediments. AB - Analysis of adenosine triphosphate (ATP) from surficial sediment layers in two antarctic lakes and two temperate lakes showed a high degree of similarity in spite of differences between trophic state, mictic state, or geographic location. Adenosine triphosphate was found at all levels sampled in temperate lake sediment cores but occasionally was present only in surficial layers of antarctic cores. Surficial sediment layers from antarctic lakes contained high chlorophylla (Chla) levels due to the extensive benthic algal mats which occur there. In some antarctic cores, Chla was detectable in deep, old mat layers, whereas Chla was not found in any of the temperate lake cores. Antarctic lake sediments appear to be unique environments where Chla molecules can remain intact for long periods of time due to low light, temperature, and microbial activity. As such, these lakes are important natural laboratories where a long history of microbial interactions can be studied without metazoan perturbation effects. Although there was much variability in concentration of Chla and ATP between samples, there appears to be no relationship between Chla or ATP levels to mictic or trophic states of the lakes. These data suggest that sediment microbial communities may be independent of environmental and biological properties of the overlying water masses. PMID- 24221650 TI - A model for the density ofAeromonas hydrophila in Albemarle Sound, North Carolina. AB - The abundance ofAeromonas hydrophila was measured monthly at 29 sites in Albemarle Sound, North Carolina and its tributaries from April 1977 through July 1979. Simultaneous measurements included heterotrophic plate count bacteria, fecal coliform bacteria, and 18 physical and chemical parameters. Using only 6 water quality parameters, multiple correlation and regression analysis of the data produced a best-fit regression which explained 38% of the variation observed inA. hydrophila density. The 6 water quality parameters included dissolved oxygen, temperature, orthophosphate, chlorophyll A trichromatic, total Kjeldahl nitrogen, and ammonia. Heterotrophic plate count bacteria and fecal coliform densities were highly correlated withA. hydrophila density, but made the model very unstable. The model was successfully tested against similar data collected for 2 other North Carolina reservoirs, Lake Norman and Badin Lake. Data from 10 sites in Badin Lake over 18 months and from 7 sites on Lake Norman over 5 months were not significantly different from the Albemarle Sound model. Conditions of water quality that may give rise to "blooms" ofA. hydrophila will simultaneously contribute to the probability of increased epizootics in fish in the southeastern United States. PMID- 24221651 TI - Changes in water and sediment bacterial community structure in a lake receiving acid mine drainage. AB - Water and sediment bacterial communities in a freshwater impoundment were studied over a 13-month period for stress-related responses to a point source of acid mine drainage (AMD). Comparisons of community structure were made on collections taken at the mouth of the acid stream, at a point 2 km downstream, and at the mouth of an uncontaminated stream. Monthly measurements of pH and specific conductance indicated the expected decrease in the AMD pollution with increasing distance from the source. Acridine orange direct counts did not differ significantly among the sites; however significantly fewer viable heterotrophs were observed by plate counts at the acid impacted station relative to the uncontaminated site. The diversity of the communities was significantly lower at the sites receiving mine drainage as compared with the unaffected station, and comparisons of community similarity showed that collections from the impacted sites were more like each other than like the control site. The assemblage at the latter site contained many bacterial guilds not found at the contaminated sites. The guilds unique to the control site showed a reduced in vitro ability to tolerate heavy metals as compared with the general community. PMID- 24221652 TI - Occurrence ofCandida albicans in fresh gull feces in temperate and subtropical areas. AB - The occurrence ofCandida albicans in fresh gull (Larus spp.) feces was compared in temperate and subtropical locations. Of 239 fresh samples, 133 were obtained in southeastern Connecticut and 106 from different sites on the southeastern and central western coasts of Florida. Overall, 60% of all feces containedC. albicans. Of the Connecticut samples, 78% were positive, whereas 38% of the Florida samples revealed the presence of the yeast. Only 1 of 24 samples of fresh brown pelican feces containedC. albicans. Differences inC. albicans occurrence in birds in various locations was ascribed to variations in habitat and feeding behavior. Samples of water from a municipal reservoir in Connecticut were routinely positive, with an average cell density of 20/liter. Two fresh gull samples obtained on the reservoir bank containedC. albicans at an average cell concentration of 5, 200/g. The frequency ofC. albicans in gull droppings was higher than reported by others, and the yeast is common in temperate waters. These findings have important public health implications. PMID- 24221653 TI - A membrane adsorption-SEM technique for observing neuston organisms. AB - A technique to observe neuston organisms, combining membrane adsorption and scanning electron microscopy, is described. Bacteria, algae, and protozoa collected from the surface of 2 freshwater ponds using this methodology appeared well preserved by the fixation and dehydration procedures used. PMID- 24221654 TI - Detection of mycoparasitism by infrared photomicrography. AB - The fungusTrichoderma harzianum which parasitizes its hostRhizoctonia solani (AG 1-6) was observed under a light microscope and the interaction sites photomicrographed with infrared film. Bright regions indicating infrared irradiation were observed at the interaction sites, apparently due to the high parasitic activity occurring there. The possible use of infrared photomicrography in cell-cell interactions is discussed. PMID- 24221655 TI - Haploid plants regenerated via anther culture in wild barley (Hordeum spontaneum C. Kock). AB - Androgenic plants have been obtained via anther culture in four natural populations of Hordeum spontaneum. Microscopic observations revealed that androgenesis started with the formation of two vegetative-type nuclei derived from the mitotic division of the uninucleate microspores. In this species androgenesis was affected by the type and concentration of the sugars added to the culture medium: the highest response (17% of callusing anthers) was observed on media containing 80 g l(-1) maltose. The highest production of androgenic plants (per 100 anthers, 5.9 green and 4.3 albino plants) was obtained from callus grown on these same media. About half of the green plants regenerated were haploid, while the others were diploid and set seed. PMID- 24221656 TI - Plant regeneration from protoplasts of Panax ginseng (C.A. Meyer) through somatic embryogenesis. AB - Protoplasts of Panax ginseng were isolated from embryos obtained from the 4-year old embryogenic cell line KCTC PCL 49031 which was derived from a zygotic embryo. High protoplast yields of 22-25 * 10(6) protoplast / g tissue were obtained following 5-6 h digestion with 2% Cellulysin, 1% Pectinase and 1% Macerasae in half strength Murashige and Skoog's medium containing 12% mannitol. A plating density of 1*10(5) protoplasts /ml was found optimal for protoplast culture. An initial division frequency of 10% was obtained in an agarosegelled defined medium. Myo-inositol (6%) was found to be the most suitable osmoticum. Somatic embryos were formed from protoplast derived embryogenic callus, which regenerated into plantlets. PMID- 24221657 TI - Shikonin production and secretion by hairy root cultures of Lithospermum erythrorhizon. AB - Hairy root cultures of Lithospermum erythrorhizon were established by transformation of in vitro grown shoots with Agrobacterium rhizogenes 15834. Hairy roots cultured on Murashige and Skoog solid medium did not produce any red pigments. However, the hairy roots cultured in Root Culture solid or liquid media produced a large amount of red pigments, which were released to the medium. The addition of adsorbents to the culture medium stimulated shikonin production by ca. 3-fold. Using this method an air-lift fermenter system was established, equipped with a XAD-2 column, which continuously produced ca. 5 mg/day of shikonin during a period of more than 220 days. PMID- 24221658 TI - Agrobacterium-mediated transformation and regeneration of kiwi fruit. AB - Genetically transformed kiwi fruit (Actinidia deliciosa) plants were obtained from hypocotyl and stem segments co-cultured with Agrobacterium tumefaciens strain EHA101 harboring a binary vector, pLAN411 or pLAN421, which contained the neomycin phosphotransferase II (nptII) gene and the beta-glucuronidase (GUS) gene. After co-culturing with the A. tumefaciens, the hypocotyl or stem segments were cultured on a selection medium containing 25MUg/ml kanamycin and 500MUg/ml Claforan. After one month in culture, shoots had regenerated from the cuttings. Green shoots were analyzed for NPTII activity and GUS activity. Eighty-five percent of the green shoots examined expressed the nptII and GUS genes. GUS histochemical assays revealed strong GUS expression in guard cells, mesophyll cells, and trichomes. PMID- 24221659 TI - Increase of rooting ability in the woody species kiwi (Actinidia deliciosa A. Chev.) by transformation with Agrobacterium rhizogenes rol genes. AB - The woody species kiwi (Actinidia deliciosa A. Chev.), a male and late flowering clone of the cv Hayward, has been transformed by a T-DNA fragment encompassing rol A, B, C genes of A. rhizogenes. Transgenic plants, regenerated from leaf disc callus, showed the typical "hairy root" phenotype as described in herbaceous species. Explants from these plants (both leaf discs or 3 to 4 node leafy microcuttings) showed an increased ability to produce roots. Since root formation is one of the limiting factors in the vegetative propagation of woody species, the results have been discussed in relation to the use of A. rhizogenes rol genes in improving root morphogenesis in trees. PMID- 24221660 TI - Long-term optimized embryogenic cultures in durum wheat (Triticum durum Desf.). AB - Five varieties of durum wheat: Appulo, Ofanto, Latino, Creso, and Castello (Triticum durum Desf.) adapted to the semi-arid mediterranean environment have been tested for their in vitro response. Compact, embryogenic, highly regenerable calli originated from primary callus derived through proliferation of the scutellum of immature embryos explanted in the presence of 2,4 dichlorophenoxyacetic acid. Selective subculture of the white, compact, embryogenic sectors led to the establishment of long-term cultures. Regeneration occurred on hormone-free medium either via germination of somatic embryos, or via multiple-shoot formation probably due to precocious germination of somatic embryos. The three varieties, Ofanto, Creso and Appulo, were the best responding genotypes. Callus fragmentation and two subsequent transfers onto fresh medium at 7-day intervals yielded a frequency of plant regeneration of some 25-40 plantlets per gram fresh weight callus in 21 days on Murashige and Skoog's hormone-free medium. Plantlets could be efficiently established in soil, thus confirming the possibility of biotechnological approaches with varieties of this crop species. PMID- 24221661 TI - Transformation of Medicago arborea L. with an Agrobacterium rhizogenes binary vector carrying the hygromycin resistance gene. AB - Plants of Medicago arborea have been infected with Agrobacterium rhizogenes strain LBA9402 harbouring the plasmids Ri 1855 and AGS125 carrying a gene conferring resistance to the antibiotic hygromycin. About 7056 of the hairy roots showed callus formation on hygromycin-supplemented medium. Regeneration took place on antibiotic free medium only. Plantlets suitable for transfer to soil were obtained after the manual removal of most of the leaves. Plant morphology showed the usual alterations induced by the Ri plasmid; moreover, two years after soil-transfer, transformants have not flowered. Molecular analysis indicates the presence of T-DNA from both pAGS 125 and p1855. The expression of the hygromycin phosphotransferase gene allowed callus and protoplasts of transformed plants to grow on media supplemented with the antibiotic. This trait will be utilized as a marker in protoplast fusion between Medicago arborea and Medicago sativa (alfalfa). PMID- 24221662 TI - Light-inducible pigmentation in Portulaca callus; selection of a high betalain producing cell line. AB - We have established a unique betalain pigmentation system in callus cultures that originated from seedlings of Portulaca sp. 'Jewel'. Within three different 'Jewel' lines examined, one line (JR) was clearly superior with regard to callus growth rate and pigment formation. Furthermore, after ten cycles of selection of deeply colored callus patches, the selected clones contained on an average four times the amount of betalain as compared to the non-selected mother line. The colorization was induced by light, but disappeared in the dark. Pigment synthesis was detectable within 30 h after irradiation and showed positive correlation with irradiation periods. PMID- 24221663 TI - Gene transfer in plants of Brassica juncea using Agrobacterium tumefaciens mediated transformation. AB - An efficient system for gene transfer into plants of Brassica juncea var. India Mustard, mediated by Agrobacterium tumefaciens. was developed through the manipulation of the culture medium and the use of the appropriate Agrobacterium strain. High frequency shoot regeneration (90-100%) was obtained from hypocotyl explants grown on medium containing 0.9% agarose, 3.3 mg/L AgNO3 and 0.5-2 mg/L BA in combination with 0.01-0.05 mg/L 2,4-D or 0.1-1 mg/L NAA. Of all the Agrobacterium strains tested, A. tumefaciens A208-SE, carrying the disarmed Ti plasmid and a binary vector pROA93, was the most effective for B. juncea transformation. pROA93 carries the coding sequences of the NPTII and the GUS genes, both driven by a common CaMV 35S promoter in two divergent directions. Inoculated explants grown on the selection medium in the presence of 0.5 mg/L BA and 0.1 mg/L NAA gave rise to transgenic shoots at the highest frequency (9%). All Ro transgenic plants were phenotypically normal, but variation in expression patterns of the GUS gene occurred among the transgenic plants in an organ- and tissue-specific manner. Both the NPTII and the GUS genes were transmitted to the R1 seed progeny and showed co-segregation. PMID- 24221664 TI - Preparation of high molecular weight plant DNA and its use for artificial chromosome construction. AB - The availability of a substantial amount of high molecular weight DNA is an essential prerequisite for the construction of yeast artificial chromosome (YAC) libraries. Parameters concerning protoplast isolation and DNA extraction have been systematically analyzed. Conditions have been established for the obtainment of high molecular weight DNA from Arabidopsis thaliana and Nicotiana plumbaginifolia protoplasts either embedded in agarose plugs or in liquid suspension. Restriction fragments were obtained by partial and total digestion with different endonucleases, and separated by pulsed-field gel electrophoresis. Ligation of partially EcoRI-digested DNA (range 30-300 kbp) followed by transformation of yeast spheroplasts gave rise to YACs with an average size of 60 kbp. The introduction of a DNA size-selection step before ligation led to production of YACs in the range of 100-200 kbp. Clones of up to 460 kbp were obtained by blunt-end ligation of pre-selected unrestricted DNA. PMID- 24221665 TI - Rosmarinic acid formation and differential expression of tyrosine aminotransferase isoforms in Anchusa officinalis cell suspension cultures. AB - Time-course changes in rosmarinic acid (RA) formation and activities of tyrosine aminotransferase (TAT) isoforms were examined in Anchusa officinalis suspension cultures. Three TAT isoforms (TAT-1, TAT-3, TAT-4) were resolved by Mono-Q anion exchange column chromatography. The proportion of the TAT-3 activity within the total TAT activity remained high regardless of the growth stage of the cultured cells. TAT-1 activity was positively correlated with the rate of RA biosynthesis during linear growth stage of the culture cycle, while TAT-4 activity was rapidly induced in conjunction with transfer to fresh medium coincident with a transient increase in RA synthesis. Based on these results, as well as the substrate specificity of each TAT isoform, it was concluded that both TAT-1 and TAT-4 are closely involved in RA biosynthesis. TAT-1 controls conversion of tyrosine to 4 hydroxyphenyl pyruvate, and TAT-4 acts by participating in the formation of tyrosine and phenylalanine via prephenate. PMID- 24221666 TI - Effects of L-proline and post-plating temperature treatment on Maize (Zea mays L.) anther culture. AB - Comparison of different post-plating temperature regimes with a control treatment (27 degrees C) revealed that a short-term cold (8/14 degrees C:2/2 days or 14 degrees C:4 days) as well as a heat treatment (30 degrees C:14 days) increased the production of embryro-like-structures (ELS) from cultured maize anthers. The beneficial effects of short-term cold treatments were magnified 2-3 times when L proline (PROL) was added to the induction medium (125-500 mg/L). In the best treatment (14 degrees C:4 days, 125 mg/L L-proline) one genotype produced 143.5 ELS/100 anthers. Anthers subjected to high temperature (30 degrees C:4 days, 30 degrees C:7 days, 30 degrees C:14 days) generally showed a lower response than did cold treated anthers, although genotypic differences were observed. Regeneration frequency did not appear to be affected by the presence of L-proline in the induction medium. PMID- 24221667 TI - A simple procedure for the isolation of pure nuclei from carrot embryos in synchronized cultures. AB - A simple method is presented for the isolation of nuclei from somatic embryos of carrot (Daucus carota L.), which is applicable to small amounts of material in synchronized culture. The method employs buffers containing a high concentration of glycerol to stabilize the structure of the nuclei. Purification was carried out by centrifugation using preformed Percoll gradients. Treatment with cell wall degrading enzymes prior to homogenization improved the efficiency of isolation and permitted a reproducible yield of nuclei. The pure preparations were obtained with an efficiency of approximately 60%. The isolated nuclei retained their morphological characteristics as demonstrated by phase - contrast and electron microscopy. Nuclear proteins displayed the expected species of histones by two dimensional gel electrophoresis. The isolated nuclei showed high RNA polymerase activity. PMID- 24221668 TI - Isochorismate hydroxymutase from Rubiaceae cell suspension cultures. AB - The enzyme catalysing the isomerisation of chorismic to isochorismic acid (isochorismate hydroxymutase E.C. 5.4.99.6) has been detected in protein preparations of various cell suspension cultures derived from plants of Rubiaceae species. PMID- 24221669 TI - A new approach to direct somatic embryogenesis in Medicago. AB - A highly efficient system for direct somatic embryogenesis is described. Leaf sections originating from young trifoliate leaves of Medicago falcata line 47/1-5 and Medicago sativa line No2/9R, directly produced embryos after cultivation in liquid B5IV induction medium. In comparison with indirect somatic embryogenesis the system omits the callus stage and thus allows shortening of the process of somatic embryogenesis in alfalfa by 35-40 days. It permits the avoidance of secondary changes occurring during the process of dedifferentiation. A modified B5/3H medium containing Polyethylene Glycol 6000 promoted embryo development from globular up to torpedo stage. It was clearly shown that 2.5% Polyethylene Glycol stimulated this process for both H. falcata 47/1-5 and M. sativa No 2/9R. Maturation of torpedo stage embryos was carried out on solidified or liquid abscisic acidcontaining medium. A 30MUM abscisic acid concentration was optimal in allowing one embryo to yield one plant. Somatic embryo conversion to plants and plant regeneration was performed on Murashige and Skoog medium. Regenerated plants showed a normal morphology. PMID- 24221670 TI - Desiccation of microspore derived embryos of oilseed rape (Brassica napus L.). AB - Microspore-derived embryos from Brassica napus L. were dried to less than 15% moisture and stored dry for a minimum of 7 days. Successful plant regeneration was observed when embryos at the cotyledonary stage of development were treated with 50 uM ABA for 7 days prior to desiccation. Solid agar or liquid medium gave similar results. The rate of drying of embryos after ABA pretreatment had only minor effects on embryo survival, but for untreated embryos, slow drying gave a small degree of survival. These results are very comparable to those with alfalfa somatic embryos, suggesting that the ABA treatment of cotyledonary stage embryos may be broadly used as a pretreatment for inducing the expression of desiccation tolerance in plant embryos. PMID- 24221671 TI - Plant regeneration from protoplasts of embryogenic cell suspensions of Coffea arabica L. cv. caturra. AB - Coffee plants were regenerated from protoplasts isolated from embryogenic cell suspension cultures derived from somatic embryos of Coffea arabica L. cv. caturra. Yields of viable protoplasts ranged from 1*10(5) to 6*10(5) protoplast/g fresh weight. Protoplast preparations usually contained no contaminating cells, and when present, the number of cells never exceeded 0.1% of the total. Plating efficiencies of protoplast ranged from 1 to 10%. Embryogenic protocolonies obtained after several subcultures in a medium supplemented with 0.5 mg/l each of benzylaminopurine, 2,4-dichlorophenoxyacetic acid and naphtaleneacetic acid, were transferred to a medium lacking plant growth regulators. Well differentiated embryos were formed in selected protocolonies that contained many embryos-like structures. Approximately 70% of the somatic embryos developed into green rooted plantlets which were succesfully transferred to vessels containing sterilized scoria. Plants grown for two months in scoria were finally transferred to greenhouse. PMID- 24221672 TI - Enhanced codeine and morphine production in suspended Papaver somniferum cultures after removal of exogenous hormones. AB - Morphine and codeine accumulation in Papaver somniferum suspension cultures increased markedly after removal of hormones from the medium. Cultures developed hormone self-sufficiency without organogenesis or development of meristemoids; enhanced synthesis of morphinan alkaloids was not dependent on formation of shoots, roots or embryos. Without exogenous hormones, maximum codeine and morphine concentrations were 3.0 mg g(-1) dry weight and 2.5 mg g(-1) dry weight respectively, up to three times higher than in cultures supplied with hormones. Hormone-deprived cells produced a higher ratio of codeine:morphine than cultures supplied with auxin and cytokinin. Improved alkaloid production was correlated with slower overall growth rate. PMID- 24221673 TI - Gene transfer into peanut (Arachis hypogaea L.) by Agrobacterium tumefaciens. AB - Introduction of foreign genes into plant tissues via Agrobacterium tumefaciens based vectors requires specific knowledge of Agrobacterium-host compatibility. Therefore, to develop a transformation protocol for peanut (Arachis hypogaea L.), five Brazilian cultivars were screened with four wild-type A.tumefaciens strains. Successful transformation was dependent on specific bacterial strain-plant cultivar interactions and strain A281 was the most effective for tumor induction. Tumors displayed hormone autonomous growth, were opine positive and contained DNA that was homologous to the T-DNA of the inciting strain. Tumors induced on seed and seedling explants by A281 (pTD02) also expressed the reporter genes gus and npt-II contained in the binary vector. These results show that peanut is a permissive host for the acceptance of genes from specific A.tumefaciens gene vectors. PMID- 24221674 TI - A novel technique to overcome browning in tissue culture. AB - Experiments conducted using Dioscorea alata L. revealed that an exudate from the cut end of the explants was responsible for browning of the culture medium. Browning did not affect growth of roots and shoots when explants were cultured in a large volume of medium, but in a small volume it was lethal. Sealing the cut ends with paraffin wax was found to control browning by preventing exudation. This simple technique permitted establishment of cultures in a small volume of medium in about 90 percent of the cases, while in unsealed cultures lethal browning was recorded in 80 percent of the cases. The advantages of this technique over other methods of controlling browning are discussed. PMID- 24221675 TI - Plant regeneration through somatic embryogenesis from suspension culture-derived protoplasts of Paspalum scrobiculatum L. AB - Protoplasts were released from embryogenic suspension culture of Paspalum scrobiculatum and cultured in either liquid or semisolid KM medium supplemented with 2,4-D in the dark at 24 degrees C with or without a feeder layer. Cell wall formation was observed in 75% of the plated protoplasts. Microcolonies developed after 10 d of culture, which in turn formed callus upon transfer to M-2 medium (Nayak and Sen, 1989). The highest plating effeciency (ca 7%) was obtained in thin-layer liquid culture. The macrocalli formed somatic embryos which regenerated to plantlets. The plantlets were grown to flowering plants upon transfer to soil. PMID- 24221676 TI - Bioreactor culture of heterotrophic sandalwood (Santalum album L.) cell suspensions utilizing a cell-lift impeller. AB - Growth and phenolic production by two heterotrophic suspension cultures (SW-1 and SW-2) of sandalwood cultivated in a 2.5 L bioreactor were investigated. Cultures of SW-1 cell suspensions resulted in a maximum phenolic content of 32.5 mg L(-1) compared to 12.5 mg L(-1) produced by SW-2 cell suspensions. Fresh weight doubling time (Td) was 5.8 days and the specific growth rate (MU) was 0.12 d(-1) during exponential growth for both cell lines. The pH of the culture medium decreased from 5.5 to 3.5 during the exponential growth phase of SW-1 and SW-2 cell suspensions. The dissolved oxygen content also dropped steadily during culture and remained at 40% throughout exponential growth phase. These results should provide a basis for developing sandalwood cell cultures for bioproduction of useful compounds. PMID- 24221677 TI - Medicarpin and maackiain 3-O-glucoside-6'-O-malonate conjugates are constitutive compounds in chickpea (Cicer arietinum L.) cell cultures. AB - The pterocarpan phytoalexin conjugates medicarpin 3-O-glucoside-6'-O-malonate and maackiain 3-O-glucoside-6'-O-malonate were isolated from cell suspension cultures of chickpea (Cicer arietinum L.) cultivar ILC 3279 and structurally elucidated. Both pterocarpan conjugates are constitutive metabolites of the chickpea cell cultures. Upon application of an elicitor from yeast to the cell cultures a substantial increase in the level of the phytoalexin aglycones medicarpin and maackiain was observed although a delayed but significantly higher rise of the conjugates also occurred. The significance of the pterocarpan conjugates for phytoalexin production is discussed. PMID- 24221678 TI - Airs, waters and places. PMID- 24221679 TI - Water quality of runoff from revegetated mine spoil. AB - Permanent vegetation plots were established on mixed overburden and topsoiled overburden on a lignite test pit in eastern Texas in 1982. Vegetative treatments included two grass-legume treatments [switchgrass (panicum virgattun) - sideoats grama (Bouteloua curtipendula) - subterrancan elover (Trifolitun subterranean) and litte bluestem (Schizachyriun scoparium) - sideoats grama (Bouteloua curtipendula) - Illinois hundleflower (Dessmanthus illinoiensis)] and three monocultures [Coastal bermudagrass (Cynodon dactylon), bahia grass (paspalum notatum) and yellow Indiangrass (Sorghastrum nutans)]. Water was applied to the 0.5m(2) plots using a sprinklertype rainfall simulator and quality of runoff was determined for each plot. Parameters analyzed included: settleable solids, total filterable solids, sediment production, infiltration rate, nitrites, nitrates, total iron and total manganese. Topsoiling significantly increased inliltration and significantly decreased filterable sediments, sediment production and settleable solids. The hydrologie qualities of the switchgrass-sideoats grama subterranean elover mixture coincided closely with those of the Coastal bermudagrass monoculture. PMID- 24221680 TI - Generating productive topsoil substitutes from hard rock overburden in the southern appalachians. AB - Natural soils on steeply sloping landscapes in the Appalachian coal fields of Virginia. West Virginia. Kentucky, and Tennessee are often thin, rocky, acidic and infertile, making the topsoiling of surface mined sites impractical in many cases. Topsoil substitutes composed of blasted rock fragments are commonly used in this region. The proper selection and placement of designated topsoil substitutes is therefore critical to long term reclamation success. These mine soil surfaces are not in equilibrium and with the surface environment, and it is quite difficult to diferentiate among dissolution, adsorption, desorption and precipitation reactions as these surfaces weather with time. Severe compaction limits the productivity of many otherwise suitable topsoil substitutes. A minimum non-compacted thickness of 1 m is desirable to insure long run mine soil productivity for a variety of post-mining land uses. Significant changes in the physical, chemical, and mineralogical properties of mine soils occur within one year after placement. Mine soils high in silt content often form hard vesicular surface crusts, particularly when left unvegetated. The long term survival of plant communities on these mine soils is dependent upon mine soil organic matter accumulation and N and P cycling. Little is currently known about N and P dynamics in these mine soils, but P-fixation is a profound problem in high Fe(3-) spoils. Revegetation practices that were designed to meet 2-year bond release requirements may not he sufficient to meet new 5-year release standards. Hard rock derived mine soils can often equal or exceed native topsoil in productivity and post mining land use potential. PMID- 24221681 TI - Acid mine drainage from inactive eastern coal operations. AB - The most widely used technique for abatement of acid drainage from inactive surface mines and refuse disposal areas is revegetation of a soil cover applied to the waste material. Nonetheless, acid production often persists and in some cases, limits establishment of vegetation. This paper reports on several field studies intended to determine the location of pyrite oxidation zones and migration pathways of oxidation products at inactive spoil and refuse sites.Oxygen required for pyrite oxidation is believed to he provided in the gaseous state from the atmosphere. Therefore, the oxygen concentration in unsaturated mine waste should provide an estimate of the weathering tendency in the local environment. We are currently monitoring gas composition in refuse and spoil at six sites. Barren refuse appeared to be oxygenated (>2% 02) in a shallow zone extending less than 1 metre below the surface during most of the year. Preliminary data from coal spoil showed that oxygen can be available throughout the unsaturated thickness, even at a revegetated site. Gas composition varied vertically and laterally at a single site and also appeared to show seasonal dependence.Hydrologic factors are also important in acid production and transport. Discharge monitoring alone does not adequately describe the mass transport of acid products through the spoil. For example, at one reclaimed mine the mean sulfate content in six monitoring wells ranged from 24% to 240% of the mean concentration at the discharge point. Sources of recharge and relative flow rates determine the contribution of a particular zone to overall discharge quality.These basic studies of acid production and transport indicate some shortcomings of standard reclamation practices at certain sites. This information will he used to develop alternative abatement technology designed to mitigate acid production at the source. PMID- 24221682 TI - Reclamation techniques in southwestern wyoming. AB - Bridger Coal Company operates a 5.8 million tpy surface coal mine thrity five miles northeast of Rock Springs. Wyoming. Approximately 20.000 acres are under permit, with disturbance over the life of the mine projected to reach 10,000 acres. Located on the western rim of the continental divide, the mine receives less than 8.5 inches of precipitation annually. Soils in the area are coarse textured. and problems associated with elevated salinity and sodicity arc encountered.A variety of common reclamation techniques have been modified to reflect these conditions. Soil horizons are segregated during salvage operations (the surface six inches as topsoil and the balance as subsoil). Unsuitable materials are not salvaged. Direct application of soil is used (over 130 acres in 1983) to maximize native plant regeneration and conserve soil fertility. Inter seeding of seeding failures has proven to be significantly more successful than chisel plowing and reseeding. Broadcast seeding has been ineffective because of strong winds, and a no till drill has been modified to handle diverse seed mixes and rock conditions. The utility of fertilization under typically xeric moisture regimes is being evaluated. A research project has been initiated to assess establishment of a predominately native, diverse seed mix under irrigation, as well as to determine irrigation rates and duration. PMID- 24221683 TI - Microbial relationships in surface-mine revegetation. AB - The establishment and interrelationships of microorganisms with soil and plant processes during reclamation are greatly influenced by the composition of the planting medium and vegetation practices. While in some instances the parent material may be used as the vegetation medium, the practice of topsoiling, particularly the direct haul method, may be beneficial in introducing microorganisms and improving the quality of the plant growth medium of spoils that are chemically or physically less desirable than the native soils. The influence of different vegetation types on soil development on surface mines may be a reflection of physioiogical differences that affect microbial development in the rhizosphere. Such differences include levels of carbohydrate translocated to the root system and/or released into the surrounding soil; the plant's effectiveness as a mycorrhizal host; and the rate of degradation of plant residues. It has become apparent that microbial interactions are an important part of plant and soil processes in reclamation. While some of the microorganisms important in plant growth and soil development can be introduced readily by management practices, the majority usually are disseminated by natural means and only gradually become a part of the microbial population. More research is needed on developing new methods or refining current procedures for early introduction of these microorganisms in reclamation practices. PMID- 24221684 TI - Forage production and quality as influenced by amended quartz sand-tailings following phosphate mining. AB - Quartz-sand tailings is a waste product from the Florida phosphate mining industry. Individual tailings disposal areas may occupy 20 to 60 ha and support no vegetation. A split plot field experiment was conducted on a sand tailings deposit to study the effect of various amendments on yield, quality, and mineral concentrations of 'Callie' bermudagrass (Cynodon dactylon var.aridus Harlan et de Wet) and 'Siratro' [Macroptilium atropurpureum (DC) Urb]. The two species were established on nine treatments: one sand-tailings control (SC); three with air dried phosphatic clay (PC) at 110, 225, and 340 Mg ha(-1); and three with overburden (OB) at 448, 1,120, and 1,800 Mg ha(-1). All PC and OB treatment rates contained air-dried sewage sludge (SS) at 45 Mg ha(-1) and were all roto-tilled to a 20 to 25 cm depth. There were two additional treatments of OB at 1800 Mg ha( 1) without SS, with and without roto-tilling into sand tailings. Callie established slower (P<0.05) on SC and OB, than on treatments containing SS and/or PC. However, after the root system developed, yields were similar on all sand tailings treatments. Crude protein andin vitro organic matter digestion for Callie and Siratro did not differ between soil treatments, but Siratro was generally superior to Callie in forage quality. Forage concentrations of P, K, Ca. Mg, Mn, and Zn were adequate in both species for good cattle growth on all treatments. However, Cu tended to be low in Siratro for plant and cattle growth. Once root systems were well established, good yields of quality forage with suitable mineral concentrations were produced on regularly fertilized, quartz sand tailings. PMID- 24221685 TI - Reclamation of bentonite mined lands in the northern great plains. AB - Ninety percent of the nation's supply of bentonite is mined in Montana, South Dakota and Wyoming. These lands are difficult to reclaim because of the chemical and physical properties of the soil/spoil material and the arid/semiarid climate of the area. Replacement of the limited topsoil available has shown some benefit but supplies are generally inadequate. The use of inorganic amendments, such as sulfuric acid, gypsum, calcium chloride, vermiculite and perlite, have not shown consistent benefits in plant establishment and growth. Organic amendments; sawmill wood residues, straw and manure, have provided the greatest benefits in the reclamation of bentonite mined lands. Cultural and management practices are important in determining the long-term success of these reclaimed lands. Reclamation technology development for bentonite mined lands is recent and limited and the refinement and application of such technology will depend on increased activity and cooperation among researchers, regulators and the mining industry. PMID- 24221686 TI - Myosin heavy chain synthesis in white trunk muscle of cod (Gadus morhua) fed different ration sizes. AB - In this study the expression of myosin heavy chain was investigated at the messenger RNA and protein level of the muscle ribosome. Cod (Gadus morhua) weighing 80 g were fed for 70 days eitherad libitum or with rations consisting of 75%, 50%, or 25% of thead libitum food intake. Protein and RNA contents of the ribosome from the white trunk muscle decreased with the diminished ration sizes. Myosin heavy chain content relative to total ribosome protein increased with the 50% ration size but fell again to thead libitum level at 25%. Expressed relative to RNA, a decrease in the protein content occurred in parallel with the decreasing ration size. The amount of protein/total muscle homogenate fell with diminished ration sizes, and that of myosin heavy chain/mg of protein remained unchanged with a slight increase at the 25% food energy intake. The messenger RNA for myosin heavy chain (relative to poly(A)(+) messenger (RNA) was increased in response to the decreased ration size but was decreased when calculated per g wet weight of the muscle. The changes in messenger RNA for myosin heavy chain were less pronounced than those of the protein itself. The levels of gene transcription and translation for myosin heavy chain were affected to a lesser extent by the low food intake than the synthesis of total RNA and protein. Immunological methods and messenger RNA hybridization to cloned DNA for myosin heavy chain permitted the precise determinations of the events taking place during a food-energy supply shortage. Translation appeared to diminish prior to changes in messenger RNA concentrations. PMID- 24221687 TI - Energetics of swimming in fishes using different methods of locomotion: I. Labriform swimmers. AB - The patterns relating rates of oxygen consumption to steady sustained and prolonged swimming at different speeds were determined in adults or near adults of two species of marine fishes that use the labriform mode of swimming (labriform swimmers). Effects of acute temperature changes on these patterns were measured. Species were the shiner surfperch,Cymatogaster aggregata and the senorita wrasse,Oxyjulis californica.Metabolic data were analyzed three different ways. The first (method of Brett) was based upon mass specific oxygen uptake and length specific swim speed; data in this form were analyzed both as best-fit power functions and as the mathematically equivalent least squares linear regressions for semi-log plots. The second and third methods were based upon drag based hydromechanical theory concerning power requirements for swimming in fishes: total metabolic ratesvs. absolute swimming speeds, analyzed both as best fit power functions and least squares linear regressions for log-log plots.The main finding, demonstrated by all three methods of calculation, was that the slopes of all regression lines (both semi-log and log-log) and the exponents of almost all power functions (five out of six) were very low. The Brett method applied to subcarangiform swimmers usually produces slopes averaging 0.36 (using base-10 logarithms). The slopes calculated by that method in the present study were 0.02-0.08. Low slope values could result from the interactions of many factors. Additional data are needed to determine which combinations of factors actually produced them. On this basis metabolic rate data on intact labriform swimmers, by themselves, appear unusable as empirical tests of theory based predictions concerning power requirements for fish swimming. PMID- 24221688 TI - Relationships between dietary ascorbic acid status and deficiency, weight gain and brain neurotransmitter levels in juvenile rainbow trout,Salmo gairdneri. AB - A study was conducted to determine the interrelationships between dietary ascorbic acid (AA) concentrations, brain neurotransmitter levels and weight gain in juvenile rainbow trout. At the end of 4 weeks and until the end of 12 weeks of feeding test diets of varying AA concentrations (0-320 mg AA/kg diet), increased weight gain was noted in fish fed the AA-free diet. However, by the end of 13 weeks and until the end of the experiment this phenomenon was no longer evident; instead the fish showed the more classical deficiency signs of anorexia and decreased weight gain. After 12 and 24 weeks, there were no significant differences in brain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) or dopamine (DA) between fish reared on the different test diets. However, after 12 weeks of feeding the test diets, brain 5-HT, brain AA and weight gain were significantly correlated with one another. No such relationships were found for brain NE or brain DA. After 24 weeks of feeding the diets, the relationships between brain 5-HT, brain AA and weight gain were no longer apparent. Similarly, after 24 weeks brain NE and DA were also unrelated to brain AA and weight gain. These results provide evidence that in very young rainbow trout, AA deficiency, brain 5-HT levels and weight gain were related. However in fish reared on the diets for 24 weeks these relationships were no longer evident. PMID- 24221689 TI - The liver parenchymal cells of rainbow trout (Salmo gairdneri) endocytose mannose terminated glycoproteins. AB - A mannose-terminated glycoprotein,(125)I-invertase, was taken up and degraded by isolated rainbow trout liver cells at 12 degrees C. The uptake was inhibited by EGTA and no degradation occurred in the presence of ammonium ions. The liver cell suspension was fractionated by differential centrifugation in parenchymal and nonparenchymal cells, respectively. The parenchymal liver cells seemed to be the most active cells in uptake of labelled invertase bothin vitro andin vivo. Only negligible amounts of ligand were recovered in the nonparenchymal cells. Internalization of(125)I-invertase at different temperatures was demonstrated indirectly by releasing surface-bound ligand with EGTA. Ligand was internalized even at 0 degrees C in trout liver cells.In vitro uptake of(125)I-invertase was inhibited by excess unlabelled invertase, by mannan and by N acetylglucosamine.These data suggest that invertase is endocytosed by a mannose specific pathway by the parenchymal liver cells of rainbow trout. PMID- 24221690 TI - Oxidative metabolism in a teleost,Anabas testudineus Bloch: effect of testosterone and estradiol-17beta on hepatic enzyme activities. AB - Testosterone (T) administration to maleAnabas testudineus significantly stimulated the activities of cytochrome oxidase, alpha-glycerophosphate dehydrogenase (alpha-GPDH) and Mg(2+) adenosine triphosphatase (Mg(2+) ATPase) and inhibited lactate dehydrogenase (LDH), cytosolic and mitochondrial malate dehydrogenases (MDH). The activities of succinate dehydrogenase (SDH), glucose-6 phosphate dehydrogenase (G-6-PDH) and catalase were unaffected by testosterone treatment. Administration of estradiol-17beta (E2) in female fish, significantly stimulated cytochrome oxidase activity, inhibited Mg(2+) ATPase, SDH, catalase and cytosolic and mitochondrial MDH activity, and was without effect on other enzymes studied.The simultaneous injections of actinomycin D or chloramphenicol and T or E2 prevented the hormonal influence on hepatic enzyme activities. The present study demonstrates that inA. testudineus sex steroids influence hepatic oxidative metabolism by a mechanism sensitive to the action of inhibitors of protein synthesis. PMID- 24221692 TI - An analysis of the ion-exchange characteristics of fish-egg chorions. AB - The chorions of rainbow trout were investigated to measure their ion-exchange characteristics. These characteristics have been incorporated into a model, based on ion-exchange theory, which attempts to describe interactions between chorions and a range of water qualities, in terms of the distribution of K(+). The model was tested by comparing predicted K(+) accumulation by chorions with that actually measured in experimental conditions. The model successfully predicted the influence of combinations of K(+) and Ca(2+) on K(+) accumulation, and was able to predict the direction of changes in K(+) accumulation in the presence of aluminium and low pH. PMID- 24221691 TI - Glycogenolytic action of glucagon-family peptides and epinephrine on catfish hepatocytes. AB - Glycogenolytic effects of salmon and mammalian glucagons, salmon glucagon-like peptide (GLP) and epinephrine were studied on liver cells isolated from catfish (Ictalurus melas). In spring and summer, salmo-glucagon (3*10(-10) to 3*10(-8) M) was more effective than its mammalian counterpart in the stimulation of glucose release and cAMP synthesis in hepatocytes. GLP was less potent as compared to both glucagons. gamma-amylase activity was not affected by the treatment with either glucagon-family peptides or epinephrine.The comparison of the glycogenolytic effects of salmon glucagon to those of epinephrine reveals a greater potency of the latter hormone in the stimulation of cAMP synthesis, glycogen-phosphorylase activity and glucose release. Glycogen content in the liver cells was equally depleted after treatment with both of the two hormones. PMID- 24221693 TI - New developed DR detector performs radiographs of hand, pelvic and premature chest anatomies at a lower radiation dose and/or a higher image quality. AB - A newly developed Digital Radiography (DR) detector has smaller pixel size and higher fill factor than earlier detector models. These technical advantages should theoretically lead to higher sensitivity and higher spatial resolution, thus making dose reduction possible without scarifying image quality compared to previous DR detector versions. To examine whether the newly developed Canon CXDI 70C DR detector provides an improved image quality and/or allows for dose reductions in hand and pelvic bone examinations as well as premature chest examinations, compared to the previous (CXDI-55C) DR detector version. A total of 450 images of a technical Contrast-Detail phantom were imaged on a DR system employing various kVp and mAs settings, providing an objective image quality assessment. In addition, 450 images of anthropomorphic phantoms were taken and analyzed by three specialized radiologists using Visual Grading Analysis (VGA). The results from the technical phantom studies showed that the image quality expressed as IQFINV values was on average approximately 45 % higher with the CXDI 70C detector compared to the CXDI-55C detector. Consistently, the VGA results from the anatomical phantom studies indicated that by using the CXDI-70C detector, diagnostic image quality could be maintained at a dose reduction of in average 30 %, depending on anatomy and kVp level. This indicates that the CXDI 70C detector is significantly more sensitive than the previous model, and supports a better clinical image quality. By using the newly developed DR detector a significant dose reduction is possible while maintaining image quality. PMID- 24221694 TI - Aspirin and non-aspirin NSAIDs increase risk of colonic diverticular bleeding: a systematic review and meta-analysis. AB - Lower gastrointestinal bleeding is a frequent cause of hospitalization, particularly in the elderly, and its incidence appears to be on the rise. Colonic diverticular bleeding is the most common form of lower gastrointestinal bleeding and is responsible for 30-40 % of bleeding episodes. Risk factors associated with diverticular bleeding include obesity, hypertension, anticoagulants, diabetes mellitus, and ischemic heart disease. Recent studies have suggested a relationship between usage of non-steroidal anti-inflammatory drugs (NSAIDs) and colonic diverticular bleeding; however, most studies were small with wide confidence intervals. We identified studies by searching the PubMed and Scopus databases (from inception through 31 December 2012) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with fixed-effects and random-effects models. A total of six studies (five case-control studies and one cohort study) met inclusion criteria for analysis. Non-aspirin NSAIDs (NANSAIDs) and aspirin were associated with an increased risk of colonic diverticular bleeding (summary RR = 2.48, 95 % CI 1.86-3.31), with moderate heterogeneity among these studies (P heterogeneity = 0.11, I (2) = 44.4 %). Stratification to evaluate the heterogeneity found that both NANSAIDs (summary RR = 2.24, 95 % CI 1.63-3.09; 5 studies) and aspirin (summary RR = 1.73; 95 % CI 1.31-2.30; 3 studies) were associated with the risk of diverticular bleeding. Aspirin/NANSAIDs use was strongly and consistently associated with an increased risk of colonic diverticular bleeding. Further studies are needed to stratify individuals at risk of diverticular bleeding associated with the use of these agents. PMID- 24221695 TI - Hybrid sensor using gold nanoparticles and conjugated polyelectrolytes for studying sequence rule in protein-DNA interactions. AB - Protein-DNA interactions play center roles in many biological processes. Studying sequence specific protein-DNA interactions and revealing sequence rules require sensitive and quantitative methodologies that are capable of capturing subtle affinity difference with high accuracy and in a high throughput manner. In this study, double stranded DNA-conjugated gold nanoparticles (dsDNA-AuNPs) and water soluble conjugated polyelectrolytes (CPEs) are used as cooperative sensing elements to construct a suit of hybrid sensors for detecting protein-DNA interactions, exploiting the differential Forster resonance energy transfer (FRET) with and without protein binding. Through a proper selection of CPEs in terms of charge properties relative to the charge of dsDNA-AuNPs and emission wavelengths relative to the AuNP extinction peak, the hybrid sensors can be constructed into "light-on", "light-off", and "two-way" models. Protein binding can be detected by fluorescence recovery, fluorescence quenching, or both ways, respectively. The "two-way" sensor allows for detection of proteins of any charge properties or unknown charge properties. With estrogen receptor (ERalpha and ERbeta), their consensus DNA (5'-GGTCAnnnTGACC-5') element, and all 15 possible singly mutated elements (i.e., 3 possible base substitutions at each of 1 to 5 positions from left to right of the 5' end half site, GGTCA), we have demonstrated the accuracy of the hybrids sensors for determination of binding affinity constant, binding stoichiometry, and site- and nucleotide-specific binding energy matrix. The in vitro binding energy determined by the hybrid sensors correlates very well with the energy matrix computed from in vivo genome wide ERalpha binding data using Thermodynamic Modeling of ChIP-Seq (rank correlation coefficient 0.98). The high degree of correlation of the in vitro energy matrix versus the in vivo matrix renders the new method a highly reliable alternative for understanding in vivo protein binding in the whole genome. PMID- 24221696 TI - [Image postprocessing part 2: algorithms and workflow]. AB - Apart from various display options, a large variety of complex algorithms to analyze radiological datasets have become available by means of advanced visualization. Basic knowledge of common concepts and properties allows the physician to choose and employ these algorithms more efficiently and successfully. In addition to functionality alone, the seamless integration of these methods into the radiological workflow is of special importance. Different scenarios can be implemented to achieve this integration. Detailed information on the individual goals of an installation and on the existing infrastructure represent prerequisites for successful integration. PMID- 24221697 TI - [Value of new MR techniques in MR-PET]. AB - The unparalleled soft tissue contrast of magnetic resonance imaging (MRI) and the functional information obtainable with 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) render MR-PET well-suited for oncological and psychiatric imaging. The lack of ionizing radiation with MRI also makes MR-PET a promising modality for oncology patients requiring frequent follow-up and pediatric patients. Lessons learned with PET computed tomography (CT) over the last few years do not directly translate to MR-PET. For example, in PET-CT the Hounsfield units derived from CT are used for attenuation correction (AC). As 511 keV photons emitted in PET examinations are attenuated by the patient's body CT data are converted directly to linear attenuation coefficients (LAC); however, proton density measured by MRI is not directly related to the radiodensity or LACs of biological tissue. Thus, direct conversion to LAC data is not possible making AC more challenging in simultaneous MRI-PET scanning. In addition to these constraints simultaneous MRI-PET acquisitions also improve on some solutions to well-known challenges of hybrid imaging techniques, such as limitations in motion correction. This article reports on initial clinical experiences with simultaneously acquired MRI-PET data, focusing on the potential benefits and limitations of MRI with respect to motion correction as well as metal and attenuation correction artefacts. PMID- 24221699 TI - [New aspects on the macroanatomy of anterolateral ligament structures of the knee and the implications for Segond fractures]. PMID- 24221698 TI - [Diagnostic odyssey in progressive dysphagia]. PMID- 24221700 TI - The use of multiple-vessel, open flow systems to investigate carbon flow in anaerobic microbial communities. AB - Five vessels, connected in series, were used for a continuous flow system to model carbon flow in anaerobic microbial communities. Two such 5-vessel systems were constructed, the inflows containing 10 mM sulfate and either 10 mM glucose or benzoate. Dilution was slow (D=0.0018 h(-1) for the whole system).Analyses of dissolved organic and inorganic carbon, and of CO2 and CH4, showed that the systems attained steady states in which biomass was constant, although there was net biosynthesis in the early vessels and net mineralization in succeeding vessels.Examination of the distributions of sulfate reduction, methanogenesis, and of H2+CO2-utilizing fatty acid-forming bacteria revealed spatial separation of these functional groups of bacteria in different vessels of the array, resembling the vertical spatial separation found in many natural sediments. Such model systems should, therefore, prove valuable in investigating the many microbial activities that contribute to the flow of carbon in anaerobic microbial communities. PMID- 24221701 TI - Microbial diversity of Minnesota peatlands. AB - Microbial diversity, numbers, and metabolic activities in Minnesota peatlands were investigated using a variety of microbial enrichment and enumeration procedures together with radioisotopic measurements of microbial degradative processes. Minnesota peatlands were shown to contain large microbial populations of wide metabolic diversity. Direct counts of bacteria using epifluorescence microscopy indicated bacterial populations of about 10(8) ml(-1) of peatland water, irrespective of depth. Radioisotopic most-probable-number (MPN) counts of heterotrophs able to mineralize(14)C-labeled substrates to(14)CO2 showed significant populations of glucose degraders (10(4)-10(6) ml(-1)) as well as degraders of benzoate (10(2)-10(3) ml(-1)), 2,4-dichlorophenoxyacetate (10(2) 10(5) ml(-1)), and sphagnum (10(3)-10(7) ml(-1)) in the various peatlands examined. The MPNs of NO3 (-) reducers varied from 10(3)-10(6) ml(-1), SO4 (-) reducers from 10(2)-10(3) ml(-1), methanogenic bacteria from 10(3)-10(6) ml(-1), and methane oxidizers from 10(3)-10(4) ml(-1), depending on sampling site and depth. Eighty pure cultures of aerobic bacteria and fungi were isolated from Minnesota peats. Most of those cultures tested were able to grow on at least 20 organic compounds (carbohydrates, aromatic molecules, hydrocarbons, etc.) as sole sources of carbon and energy. One isolate, aBacillus, was able to fix atmospheric N2. Several of the isolates were able to mineralize(14)C-labeled lignin. PMID- 24221702 TI - Amino acid assimilation and respiration by attached and free-living populations of a marinePseudomonas sp. AB - The uptake kinetics of leucine and the assimilation and respiration of leucine, glycine, glutamate and arginine by a marinePseudomonas sp. was evaluated to determine whether the uptake and efficiency of substrate utilization of free living bacteria differed from that of bacteria associated with surfaces. Bacteria were allowed to attach to plastic substrata with known hydrophilicities, as measured by advancing water contact angle (theta A); these were Thermanox, poly(vinylidene fluoride), poly(ethelene) and poly(tetrafluoroethylene). The assimilation and respiration of surface-associated bacteria depended on the amino acid and substratumtheta A, but assimilation by surface-associated cells was generally greater than and respiration was generally less than that by free living bacteria. The uptake kinetics with leucine demonstrated that the half saturation constant (K) of surface-associated bacteria was greater than that for free-living cells. The Vmax values for surface-associated and free-living bacteria were similar, except for cells associated with poly(tetrafluoroethylene), which had a higher Vmax value. PMID- 24221703 TI - Fungi and bacteria involved in desert varnish formation. AB - Desert varnish is a coating of ferromanganese oxides and clays that develops on rock surfaces in arid to semi-arid regions. Active respiration but not photosynthesis was detected on varnished rock surfaces from the Sonoran Desert. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations, and cultivation experiments indicate that both fungi, primarily dematiaceous hyphomycetes, and bacteria are found on and within desert varnish coatings from the arid regions studied. Some fungi grow as microcolonial fungi (MCF) on rocks, and microscopic observations suggest MCF become incorporated in the varnish coating. SEM-EDAX (energy dispersive X-ray systems) analyses indicate the MCF contain 3 of the characteristic elements of varnish: iron, aluminum, and silicon. In some locations, MCF are also enriched in manganese relative to the rock substratum. Furthermore, some of the dematiaceous hyphomycetes that have been cultivated are able to oxidize manganese under laboratory conditions. It is possible that manganese-oxidizing bacteria, which are found in varnish, also play an important role in varnish formation. PMID- 24221704 TI - Analysis of the community structure of yeasts associated with the decaying stems of cactus. II.Opuntia species. AB - A survey was made of yeast species associated with the decaying pads of 3 prickly pear cacti (Opuntia phaeacantha, O. ficus-indica, andO. lindheimeri) in Arizona and Texas. Yeast communities from 12 localities were compared among localities, amongOpuntia species, and with previous data on yeast communities associated with columnar cacti. The results indicate thatOpuntia necroses contain relatively more yeast species with broader physiological abilities in their communities than columnar necroses. It is argued that differences in chemistry of the opuntias and columnar forms in concert with the insect vectors specific for these cacti account for the differences in yeast community structure. It is further hypothesized that the differences in yeast community structure have been important in the evolution and maintenance of species diversity forDrosophila species which live in the decaying stems or cladodes of various cacti. Most of the yeast community evolution in the cacti is postulated to have proceeded by evolution in situ and not by additions and replacements from outside of the system. PMID- 24221705 TI - Mass balance of heavy metal uptake by encapsulated cultures ofKlebsiella aerogenes. AB - Dialysis was employed as a method of speciating heavy metals in cultures of an extracellular polymer forming strain ofKlebsiella aerogenes. A noncapsulated strain of the same bacterium was used as a control, and a mass balance of copper, cadmium, cobalt, nickel, and manganese in batch culture at pH 4.5 and pH 6.8 and in continuous culture at pH 6.8 was constructed. Copper and cadmium were accumulated by the cell during rapid proliferation whereas all 5 metals were bound nonspecifically by extracellular polymer produced during stationary phase and at low dilution rates. The presence of extracellular polymer appeared to inhibit cellular uptake of nickel. At the lower pH, metal uptake was considerably reduced. The results are discussed in the context of metal removal in the activated sludge process of waste water treatment. PMID- 24221707 TI - Vibrios in the Louisiana gulf coast environment. PMID- 24221706 TI - Ecology and taxonomy of chitinoclasticCytophaga and related chitin-degrading bacteria isolated from an estuary. AB - A total of 103 strains of estuarine, Chitinoclastic bacteria isolated from water, and sediment samples collected from the upper Chesapeake Bay, including 17 freshwater and 11 seawater isolates, were subjected to numerical taxonomy analysis. The isolates included 44 yellow-orange pigmented strains classified asCytophaga-like bacteria (CLB) of theCytophagaceae. Salt requirement of the strains ranged from tolerance to <=1% NaCl to an absolute requirement for NaCl, with 1% NaCl satisfying this requirement. The largest phenon consisted of facultatively anaerobic, oligo-nitrophilic, and flexirubin pigment-producing freshwater and estuarine isolates, and included reference strains of bothCytophaga johnsonae Stanier andCytophaga aquatilis Strohl and Tait. Other phena, containing a smaller number of strains, comprised marine and estuarine isolates which did not produce flexirubin pigments, and required organic nitrogen for growth and for production of chitinolytic enzymes. Salt-requiring, flexirubin pigment-producing, chitin-degrading strains were, on occasion, isolated from estuarine samples and represented phena found in estuaries. Most of theCytophaga isolates, as well as chitin-degrading species not of the genusCytophaga that were isolated from Chesapeake Bay, clustered in phena representing previously described species of aerobic, zymogenic, chitinoclastic bacteria. When the frequency of occurrence of features related to environmental parameters, viz., pH, salinity, temperature range of growth, and growth on media lacking organic nitrogen, was calculated, ecological groupings of strains in the 2 major phena of CLB could be distinguished among the estuarine, chitin-degrading bacteria. PMID- 24221708 TI - Immunogold localization of acyl carrier protein in plants and Escherichia coli: Evidence for membrane association in plants. AB - Immunogold labelling was used to study the distribution of acyl carrier protein (ACP) in Escherichia coli and a variety of plant tissues. In E. coli, ACP is distributed throughout the cytoplasm, confirming the observation of S. Jackowski et al. (1985, J. Bacteriol., 162, 5-8_. In the mesocarp of Avocado (Persea americana) and maturing seeds of oil-seed rape (Brassica napus cv. Jet Neuf), over 95% of the ACP is localised to plastids. The protein is almost exclusively located in the chloroplasts of leaf material from oil-seed rape. Approximately 80% of the gold particles associated with the ACP were further localized to the thylakoid membrane of the chloroplast. Since acetyl-CoA carboxylase has been reported to be localized to the thylakoid membrane (C.G. Kannangara and C.J. Jensen, 1975, Eur. J. Biochem., 54, 25-30), these results are consistent with the view that the two sequential enzymes in fatty-acid synthesis are in close spacial proximity. PMID- 24221709 TI - A theory for inflorescence development and flower formation based on morphological and biophysical analysis in Echeveria. AB - Floral development is generally viewed as involving interactions between recently made organs and generative activity on the apical dome; one set of floral organs is thought to induce the next. To investigate such interactions, flowering in Echeveria derenbergii (J. Purpus) was studied at two levels of structure. At the larger, morphological, level the inflorescence apex is shown to have simple cyclic development. Seen from above, it elongates horizontally, then forms a transverse cleft to demarcate a flower primordium in one of two rows. The meristem then elongates at 90 degrees to its previous axis, also horizontally, and demarcates a flower in the other row. Activity on the apical surface correlates well with the nature and activity of adjacent sub-apical organs. For example, the 90 degrees shifts in elongation of the meristem correlate with that tissue's being attached, laterally, to successive large growing bracts whose bases lie at 90 degrees . Also, on the flower primordium, the five sepals arise in a spiral sequence which correlates with one of increasing age, since formation by the cleft, of the edges of the primordium.The second level of study was to test whether the developmental correlations could have a biophysical explanation. By biophysical theory, organs arise where the dome surface is structurally predisposed to bulge. This is a function of the cellulose reinforcement pattern in the surface. Successive patterns of cellulose reinforcement in isolated surface layers from floral organs were determined using polarized light. This was done for the cyclic activity of the inflorescence meristem and the development of the flower. The results indicate that patterns of cellulose reinforcement on the apical dome surface could lead to the production of organs, through local promotion of bulging of the tunica. Subsequent growth of the base of each organ stretches the adjacent dome tissue in a directional fashion. Cytoskeletal responses of these stretched cells lead to new cellulose alignments on the dome which generate the reinforcement pattern for the next round of organs. PMID- 24221710 TI - Correct glycosylation, Golgi-processing, and targeting to protein bodies of the vacuolar protein phytohemagglutinin in transgenic tobacco. AB - We used a heterologous system (transgenic Nicotiana tabacum L.) to investigate the processing, assembly and targeting of phytohemagglutinin (PHA), the lectin of the common bean, Phaseolus vulgaris L. In the bean, this glycoprotein accumulates in the protein bodies of the storage parenchyma cells in the cotyledons, and each polypeptide has a high-mannose glycan attached to Asn12 and a complex glycan on Asn60. The gene for PHA-L, dlec2, with 1200 basepairs (bp) 5' upstream and 1600 bp 3' downstream from the coding sequence was introduced into tobacco using Agrobacterium-mediated transformation (T. Voelker et al., 1987, EMBO J. 6, 3571 3577). Examination of thin sections of tobacco seeds by immunocytochemistry with antibodies against PHA showed that PHA-L accumulated in the amorphous matrix of the protein bodies in the embryo and endosperm. This localization was confirmed using a non-aqueous method to isolate the protein bodies from mature tobacco seeds. The biochemical analysis of tobacco PHA indicated that the signal peptide had been correctly removed, and that the polypeptides formed 6.4 S oligomers; tobacco PHA had a high-mannose glycan at Asn12 and a complex glycan at Asn60. The presence of the complex glycan shows that transport to the protein bodies was mediated by the Golgi complex. At seed maturity, a substantial portion of the PHA L remained associated with the endoplasmic reticulum and the Golgi complex, as indicated by fractionation experiments using aqueous media and the presence of two high-mannose glycans on some of the polypeptides. Taken together, these data show that insertion of the nascent PHA into the endoplasmic reticulum, signal peptide processing, glycosylation, assembly into oligomers, glycan modification in the Golgi, and targeting of the protein occur faithfully in this heterologous system, although transport may not be as efficient as in bean cotyledons. PMID- 24221711 TI - Regulation of malic-acid metabolism in Crassulacean-acid-metabolism plants in the dark and light: In-vivo evidence from (13)C-labeling patterns after (13)CO 2 fixation. AB - The labeling patterns in malic acid from dark (13)CO2 fixation in seven species of succulent plants with Crassulacean acid metabolism were analysed by gas chromatography-mass spectrometry and (13)C-nuclear magnetic resonance spectrometry. Only singly labeled malic-acid molecules were detected and on the average, after 12-14 h dark (13)CO2 fixation the ratio of [4-(13)C] to [1-(13)C] label was 2:1. However the 4-C carboxyl contained from 72 to 50% of the label depending on species and temperature. The (13)C enrichment of malate and fumarate was similar. These data confirm those of W. Cockburn and A. McAuley (1975, Plant Physiol. 55, 87-89) and indicate fumarase randomization is responsible for movement of label to 1-C malic acid following carboxylation of phosphoenolpyruvate. The extent of randomization may depend on time and on the balance of malic-acid fluxes between mitochondria and vacuoles. The ratio of labeling in 4-C to 1-C of malic acid which accumulated following (13)CO2 fixation in the dark did not change during deacidification in the light and no doubly labeled molecules of malic acid were detected. These results indicate that further fumarase randomization does not occur in the light, and futile cycling of decarboxylation products of [(13)C] malic acid ((13)CO2 or [1-(13)C]pyruvate) through phosphoenolpyruvate carboxylase does not occur, presumably because malic acid inhibits this enzyme in the light in vivo. Short-term exposure to (13)CO2 in the light after deacidification leads to the synthesis of singly and multiply labeled malic acid in these species, as observed by E.W. Ritz et al. (1986, Planta 167, 284-291). In the shortest times, only singly-labeled [4-(13)C]malate was detected but this may be a consequence of the higher intensity and better detection statistics of this ion cluster during mass spectrometry. We conclude that both phosphoenolpyruvate carboxylase (EC 4.1.1.32) and ribulose-1,5 biphosphate carboxylase (EC 4.1.1.39) are active at this time. PMID- 24221712 TI - Cell walls as reservoirs of potassium ions for reversible volume changes of pulvinar motor cells during rhythmic leaf movements. AB - The laminar pulvinus of primary leaves of Phaseolus coccineus L. was investigated with respect to the total K(+) content, the apoplastic K(+) content, and the water potential of extensor and flexor sections in relation to the leaf positions in a circadian leaf-movement cycle, as well as the cation-exchange properties of isolated extensor- and flexor-cell walls. Turgid tissue showed a high total but low apoplastic K(+) content, shrunken tissue a low total but high apoplastic K(+) content. Thus, part of the K(+) transported into and out of the swelling or shrinking protoplasts is shuttled between the protoplasts and the surrounding walls, another part between different regions of the pulvinus. The K(+) fraction shuttled between protoplasts and walls was found to be 30-40% of the total transported K(+) fraction. Furthermore, 15-20% of the total K(+) content of the tissue is located in the apoplast when the apoplastic reservoir is filled, 5-10% when the apoplastic reservoir is depleted. The ion-exchange properties of walls of extensor and flexor cells appear identical in situ and in isolated preparations. The walls behave as cation exchangers of hhe weak-acid type with a strong dependence of the activity of fixed negative charges as well as of the K(+)-storing capacity on pH and [K(+)] of the equilibration solution. The high apoplastic K(+) contents of freshly cut tissues reflect the cation-storing capacity of the isolated walls. We suggest that K(+) ions of the Donnan free space are used for the reversible volume changes (mediating the leaf movement) mainly by an electrogenic proton pump which changes the pH and-or the [K(+)] in the water free space of the apoplast. PMID- 24221713 TI - Subcellular compartmentation of fructose 2,6-bisphosphate in oat mesophyll cells. AB - Evacuolated mesophyll protoplasts from oat (Avena sativa L.) were fractionated by a membrane-filtration technique. This method of rapid quenching of metabolic reactions permitted estimation of the in-vivo pools of fructose 2,6-bisphosphate (Fru2,6bisP) in the cytosol, chloroplasts and mitochondria. Vacuolar Fru2,6bisP was calculated as the difference between control protoplasts and evacuolated ones. The results indicate that Fru2,6bisP is exclusively cytosol-located in oat mesophyll protoplasts. Assuming a cytosolic volume of about 2 pl per evacuolated protoplast, the cytosolic concentration there was 11 MUM if protoplasts were in darkness. Illumination of either control or evacuolated protoplasts resulted in a significant decrease in the Fru2,6bisP content within 5 min. PMID- 24221714 TI - Calcium and phytochrome control of leaf unrolling in dark-grown barley seedlings. AB - The red light-stimulated component of unrolling in sections from 7-d-old dark grown barley (Hordeum vulgare L.) leaves is inhibited by ethyleneglycol-bis-(beta aminoethyl ether)-N,N,N',N'-tetracetic acid (EGTA). A free-Ca(2+) activity of less than 40 MUM restores the ability to respond to red light, but only if supplied within 1 h of red light. Magnesium ions are an ineffective substitute. At least two processes in unrolling appear to be Ca(2+)-sensitive.Fluence response measurements indicate that the levels of the far-red-absorbing from of phytochrome (Pfr) still present 4 h after red-light treatment should be above saturation for the unrolling response; consequently, loss of Pfr does not explain the loss in effectiveness of Ca(2+) during prolonged EGTA treatment. However, if a further red-light treatment is given simultaneously with Ca(2+) addition 4 h after the initial light stimulus, then full unrolling occurs in EGTA-treated sections. These data indicate that, under normal circumstances, a functional change in the properties of Pfr must occur, uncoupling it from the transduction chain. PMID- 24221715 TI - Persistent effects of changes in phytochrome status on internode growth in light grown mustard: Occurrence, kinetics and locus of perception. AB - Extension growth of the first internode in fully de-etiolated mustard (Sinapis alba L.) seedlings (11-12.5 d old) is under the control of both the current phytochrome photoequilibrium (Pfr/P, ratio of the far-red-absorbing form of phytochrome to total phytochrome) and that established by short (<12 h) pretreatments. Plants were pretreated with either light pulses providing different calculated Pfr/P followed by dark incubations of different durations (a), or with a 12-h period of white light establishing different Pfr/P (b). After the pretreatments, the plants received either light pulses providing different Pfr/P, followed by dark incubations (c), or continuous white light with or without addtional far-red light (d). Thus, four experimental approaches were followed: (a)->(c); (a)->(d); (b)->(c) and (b)->(d). Extension growth during the second period (c or d) was not only affected by the current phytochrome status, but also by that established during the pretreatment period (a or b). The results show the existence of a long-term promotion of stem growth which persists after the end of the low Pfr/P pretreatment. This effect is different from the previously reported rapid effect of far-red light added to background white light as follows: (i) the duration of low Pfr/P required to effect a full response is longer (2.5 h); (ii) the duration of the promotion after returning to high Pfr/P is longer (approx. 24 h) and (iii) the locus of perception is mainly in the leaves, rather than the growing internode. PMID- 24221716 TI - Floral-specific polypeptides of the Japanese morning glory. AB - Polypeptides from stems, leaves, sepals, corollas, stamens and pistils of the Japanese morning glory (Ipomoea nil Roth (Pharbitis nil Chois.)) were separated by one- and two-dimensional gel electrophoresis and visualized by silver staining. The majority of polypeptides were expressed in two or more organs, while those specific to only one organ were comparatively rate. Among the polypeptides of the former class were two which appeared to be floral-specific. A 46-kDa (kilodalton) polypeptide was expressed in corollas, stamens and pistils, whereas a 32-kDa polypeptide was observed only in extracts prepared from reproductive organs. Polypeptide spots from the various organs were compared with those from leaves, and it was found that sepals and stems shared 40-50% of their polypeptides with leaves, whereas corollas, stamens and pistils shared 20% or less. The latter organs shared 120 polypeptides or roughly 15% of those identified in the floral extracts. Floralorgan-specific polypeptides comprised nearly 10% of the total floral polypeptides identified. PMID- 24221717 TI - Photoinhibition of photosynthesis in willow leaves under field conditions. AB - Chlorophyll fluorescence of leaves of a willow (Salix sp.) stand grown in the field in northern Sweden was measured on several occasions during the growing season of 1987. For leaves that received mostly full daylight, the F V/F P ratio declined roughtly 15% in the afternoon on cloudless days in July (F P is the fluorescence at the peak of the induction curve obtained at the prevailing air temperature after 45 min of dark adaptation, and F V is variable fluoresence, F V=F P-F O, where F O is minimal fluorescence). There was no decrease in the F V/F P ratio on cloudy days, while the effect was intermediate on changeable days. In view of this light dependence, together with the fact that the decline in the F V/F P ratio was paralleled with an equal decline in the corresponding fluorescence ratio F V/F M at 77K, and a similar decline in the maximum quantum yield of O2 evolution, it is suggested that the decline in the F V/F P ratio represents a damage in photosyntem II attributable to photoinhibition. Recovery of the F V/F P ratio in dim light following a decline on a cloudless day took 7 16 h to go to completion; the F V/F P ratio was fully restored the following morning. When all active leaves of a peripheral shoot were compared, the F V/F P ratio in the afternoon of a day of bright light varied greatly from leaf to leaf, though the majority of leaves showed a decline. This variation was matched by a pronounced variation in intercepted photon flux density. When leaves developed in the shade were exposed to full sunlight by trimming of the stand an increased sensitivity to photoinhibition was observed as compared to peripheral leaves. The present study indicates that peripheral willow shoots experienced in the order of 10-20% photoinhibition during an appreciable part of their life. This occurred even though the environmental conditions were within the optimal range of photosynthesis and growth. PMID- 24221718 TI - Calcium localization in oat aleurone cells using chlorotetracycline and X-ray microanalysis. AB - Calcium distribution was studied in oat caryopses. Using the chlorotetracycline method it was found that membrane-associated Ca(2+) was present in the aleurone layer. X-ray microanalysis confirmed the presence of calcium in aleurone cells; it also demonstrated the presence of considerable amounts of calcium in the cell wall surrounding these cells. PMID- 24221719 TI - A new set of regulatory molecules in plants: A plant phospholipid similar to platelet-activating factor stimulates protein kinase and proton-translocating ATPase in membrane vesicles. AB - 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, an ether phospholipid from mammals known as platelet-activating factor (PAF), specifically stimulates proton transport in zucchini (Cucurbita pepo L.) microsomes (G.F.E. Scherer, 1985, Biochem. Biophys. Res. Commm. 133, 1160-1167). When plant lipids were analyzed by two-dimensional thin-layer chromatography a lipid was found with chromatographic properties very similar to the PAF (G.F.E. Scherer and B. Stoffel, 1987, Planta, 172, 127-130). This lipid was isolated from zucchini hypocotyls, red beet root, lupin root, maize seedlings and crude soybean phospholipids. It had biological activity similar to that of the PAF, based on phosphorus content, and stimulated the steady-state DeltapH in zucchini hypocotyl microsomes about twofold. Other phospholipids, monoglyceride, diglyceride, triglyceride, oleic acid, phorbol ester, and 1-O-alkylglycerol did not stimulate proton transport. When microsomes were washed the PAF was ineffective but when soluble protein was added the PAF stimulation of H(+) transport was reconstituted. The soluble protein responsible for the PAF-dependent stimulation of transport activity could be partially purified by diethylaminoethyl Sephacel column chromatography. In the same fractions where the PAF-dependent transport-stimulatory protien was found, a protein kinase was active. This protein kinase was stimulated twofold either by the PAF or by Ca(2+). When Ca(2+) was present the PAF did not stimulate protein kinase activity. When either the PAF, protein kinase, or both were added to membranes isolated on a linear sucrose gradient, ATPase activity was stimulated up to 30%. Comparison with marker enzymes indicated the possibility that tonoplast and plasma-membrane H(+)-ATPase might be stimulated by the PAF and protein kinase. We speculate that a PAF-dependent protein kinase is involved in the regulation of proton transport in plants in vitro and in vivo. PMID- 24221720 TI - Chronology of the differentiation of cotton (Gossypium hirsutum L.) fiber cells. AB - Cotton fibers are single elongated cells that develop from epidermal cells of the ovule. The chronology of fiber differentiation was investigated using cultured ovules. Epidermal cells differentiate into fiber cells approx. 3 d before anthesis. When ovules were cultured on a defined medium, fiber growth could be initiated on ovules any time between 2 d preanthesis and the time of anthesis by adding indole-3-acetic acid and gibberellic acid to the medium. In the absence of phytohormones, fibers did not grow, and when ovules between 2 d preanthesis and anthesis were cultured without hormones past the day of anthesis and hormones then added, most ovules failed to produce fibers. The results define the timing of fiber differentiation from epidermal cells, and also define a window of time when differentiated cells are capable of further development. During this window, fiber cells are latent awaiting appropriate stimulation which in the intact plant is apparently associated with anthesis. PMID- 24221721 TI - Biochemical differentiation in the tobacco flower probed with monoclonal antibodies. AB - We have isolated a series of monoclonal antibodies that react to antigens in flowers of Nicotiana tabacum L. (tobacco) displaying specificity or preferentiality in their cell and tissue distributions. We immunized mice with extracts from tobacco flowers and then screened the hybridomas by enzyme-linked immunosorbent assay (ELISA) against extracts from leaves, sepals, petals, stamens and pistils; twenty five were chosen from the total screened. The antigens detected by about half of the antibodies were periodate-sensitive, implying that the epitopes were carbohydrate. Competition ELISA assays were used to determine if any antibodies were reacting to the same epitopes. Western blot analysis showed that while some antibodies reacted to specific bands, the bulk either failed to react or reacted to multiple bands, consistent with a glyco-conjugate nature for many of the antigens. Analysis of the spatial pattern of antigen distribution within tobacco flowers by immunolocalization showed that some antibodies recognized epitopes that were limited to very specific cells and tissues. We used the immunolocalization technique to analyze a mutant with stigmoid anthers: an antibody recognizing a pistil transmitting-tract antigen also reacted to cells in stigmoid anthers. Our results with this antibody set imply that biochemical differentiation within the tobacco flower includes cell and tissue-specific glyco-moeities, and also that similarities, at the biochemical level, exist between a normal floral organ and the abnormal organ in a phenotype with a developmental switch. PMID- 24221722 TI - Major differences in isoforms of starch-branching enzyme between developing embryos of round- and wrinkled-seeded peas (Pisum sativum L.). AB - In order to determine whether round-and wrinkled-seeded peas (Pisum sativum L.) differ in the activity and properties of starch-branching enzyme (1,4-alpha-D glucan, 1,4-alpha-D-glucan-6-glycosyl transferase; EC 2.4.1.18) in their developing embryos, essentially isogenic lines of peas, differing only at the r (rugosus) locus that confers the round (RR, Rr) or wrinkled (rr) phenotype, were studied. Activity of the enzyme rises rapidly from an early stage of development in embryos of round peas, but only at later stages in embryos of wrinkled peas. The purified enzyme from mature embryos of round peas can be resolved into two isoforms that differ in molecular weight and in their ability to branch amylose. The purified enzyme from mature embryos of wrinkled peas is a single protein with the same molecular weight and branching properties as one of the isoforms from embryos of round peas. The difference in activity of starch-branching enzyme between embryos of round and wrinkled peas is likely to be due to the absence from embryos of wrinkled peas of one of the isoforms occurring in embryos of round peas. PMID- 24221723 TI - Ionic basis of currents in somatic embryos of Daucus carota. AB - A vibrating probe was used to measure extracellular electrical currents around developing somatic embryos in two lines (RCC27, RCC48) of cultured cells of Daucus carota L. at the heart and torpedo stages. At pH 5.5, an inward current of 1.2+/-0.1 MUA.cm(-2) (n=23) was detected at the cotyledon, and an outward current of 1.0+/-0.1 MUA.cm(-2) (n=22) was found at the radicle in torpedostage embryos from the RCC27 line. At a pH of 5.75 the currents increased by 0.2-0.3 MUA.cm(-2) (n=60-62). In a few cases an additional small inward current was detected at the tip of the radicle in toepedo-stage embryos from RCC27 line. Such an inward current at the radicle seemed to appear earlier, some time after the heart stage, in embryos from the RCC48 line.Both extracellular pH measurements (using microelectrodes filled with ion-sensitive resin) and ion-substitution studies were carried out in order to ascertain the ionic composition of the currents in torpedo-stage embryos from the RCC27 line. Regions adjacent to the cotyledon and radicle, at the points of current entry and exit, were found to be more acidic by 0.02+/-0.01 (n=14) and 0.07+/-0.01 (n=12) pH units, respectively, than the bulk medium. Removal of K(+) from the medium reversibly reduced the currents to about 25% of their original value at both cotyledon and radicle. Deletion of Cl(-) decreased the currents slightly. Removal of Ca(2+) resulted in a rapid doubling of currents. Addition of either N,N'-dicyclohexylcarbodiimide or tetraethyl ammonium chloride substantially reduced overall currents, and their removal resulted in partial recovery of the currents. It is suggested that the inward current at the cotyledon is comprised largely of K(+) influx and the outward current at the radicle is mainly the result of active H(+) efflux. PMID- 24221724 TI - Emotion regulation mediates the association between ADHD and depressive symptoms in a community sample of youth. AB - The purpose of this study was to examine the longitudinal relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms, emotion regulation (ER) ability, and depressive symptoms within a diverse community sample of 277 youth, ages 9-12 (56 % male). Participants were drawn from a larger study examining adolescent risk behaviors, and completed annual assessments over 3 years. Youth ADHD symptoms were assessed at Time 1 (T1) using the parent-reported Disruptive Behavior Disorders Rating Scale, ER was assessed with the parent-reported Emotion Regulation Checklist at Time 2 (T2), and youth depressive symptoms were assessed using the self-reported Revised Child Anxiety and Depression Scales at Time 3 (T3). Analyses examined T2 ER as a mediator between T1 ADHD symptoms (including the unique contributions of inattentive [IA] versus hyperactive/impulsive [HI] symptoms) and T3 depressive symptoms. Structural equation modeling (SEM) indicated the path model specified provided an excellent fit to the data. Tests of indirect effects suggested that T2 ER appears to be a significant mechanism that underlies the relationship between T1 ADHD and T3 depression, even when accounting for T1 oppositional defiant and depressive symptoms. Furthermore, while both T1 IA and HI symptoms had significant indirect effects on T3 depression through the mechanism T2 ER, HI proved a more robust predictor of T2 ER than IA. Results of this prospective study support cross-sectional findings pointing to ER as a potential mechanism linking ADHD and depressive symptoms in youth. Clinical implications and future directions are discussed. PMID- 24221726 TI - Efficient regeneration of Brassica oleracea hypocotyl protoplasts and high frequency genetic transformation by direct DNA uptake. AB - Efficient regeneration (80%) and high frequency genetic transformation (10-33%) were achieved by culturing protoplasts isolated from hypocotyl tissues of six day old Brassica oleracea seedlings and by subjecting these protoplasts to PEG mediated direct plasmid uptake. Three different plasmid vectors carrying marker genes for resistance to methotrexate (dhfr), hygromycin (hpt) and phosphinotricin (bar) were constructed and used for transformation. Large number of normal, fertile transformants were obtained with vectors carrying hpt and bar genes. No transformants could be regenerated for resistance to methotrexate as it severely suppressed shoot differentiation. PMID- 24221725 TI - Risk factors for disordered eating during early and middle adolescence: a two year longitudinal study of mainland Chinese boys and girls. AB - Even though reliable eating disorder risk factors have been identified among adolescent girls, little is known about predictors of increased vulnerability within specific phases of adolescence or among adolescent boys, particularly in highly populated non-Western contexts. In this study, early and middle adolescent boys (n = 1,271) and girls (n = 1,415) from Chongqing, China completed validated measures of eating disorder pathology and putative risk factors at baseline and 2 years follow-up. Multivariate models for boys of each age group indicated increases in disordered eating at follow-up were predicted by higher initial body mass index, negative affect and body dissatisfaction levels as well as attendant increases in perceived appearance pressure from mass media, body dissatisfaction, negative affect between assessments. High baseline levels of reported appearance pressure from parents and dating partners contributed, respectively, to prediction models of younger and older boys. More distinct constellations of significant predictors emerged in multivariate models of early versus middle adolescent girls. Together, findings indicated body dissatisfaction and negative affect were fairly robust risk factors for exacerbations in disturbances across samples while risk factors such as perceived pressure from desired/prospective dating partners were salient only during particular phases of adolescence. PMID- 24221727 TI - Growth and disinfestation of 6 different bacteria in embryogenic suspension cultures of cotton. AB - Growth of 6 different common laboratory bacteria (Escherichia coli, Flavobacterium balustrum, Xanthomonas maltophilia, Enterobacter cloacae, Pseudomonas fluorescens, and Agrobacterium tumefaciens) in a bacterial medium, fresh plant medium, and "spent" plant media was initially measured. In all cases, bacteria grew best in the bacterial medium followed by the fresh plant medium. The spent plant medium did not support growth of the bacteria and apparently was actively toxic to bacterial cells. Proliferating, embryogenic suspension cultures of cotton (Gossypium hirsutum) were then inoculated with these 6 different bacteria. Two to three d following bacterial inoculation, embryogenic tissues were placed in various concentrations of bleach for various amounts of time, rinsed with sterile water, and placed on a bacterial culture medium. Clumps of embryogenic tissue which showed no visible bacterial growth after 3 d of culture were then transferred to an agar-solidified plant tissue culture medium to determine viability of bleachdisinfested tissues. Viable, single pieces of the disinfested embryogenic tissue were then used to reinitiate embryogenic suspension cultures. Treatment of contaminated tissue with a 1% bleach solution for 1-5 min resulted in the highest recovery of viable, disinfested tissues using 5 of the 6 bacteria. It was not possible to remove F. balustrum from clumps of embryogenic tissue without also killing the plant tissue. PMID- 24221728 TI - Characterization of embryogenic cell lines of Picea abies in relation to their competence for maturation. AB - Embryogenic cell lines of Picea abies are categorized into three groups (polar, solar, and undeveloped) based on the organization of the somatic embryos within the tissue and the ability of the somatic embryos to proceed through a maturation process when treated with ABA. The polar and the solar types consist of somatic embryos with densely packed embryonic regions subtended by vacuolated suspensors. Both types of tissue regenerate mature somatic embryos when treated with ABA. Almost all mature somatic embryos develop further into shoots or plantlets. The undeveloped type consists of somatic embryos comprised of only a few loosely aggregated cells in their embryonic regions. Mature somatic embryos were not observed with this tissue type. PMID- 24221729 TI - Mendelian inheritance of streptomycin resistance in Nicotiana plumbaginifolia. AB - In a previous study two haploid streptomycin-resistant clones of Nicotiana plumbaginifolia were isolated. The chromosome number of one of these clones has now been doubled through leaf-midvein culture and the resultant diploids were characterized genetically. Our results show that streptomycin resistance in this clone is conditioned by a recessive nuclear gene. Haploid protoplasts of this streptomycin-resistant mutant were selected for chlorate resistance. All clones obtained from the selection were deficient in nitrate reductase activity in addition to resistance to streptomycin. Genetic analysis of progeny of one of these clones revealed that the genes for streptomycin resistance and for the apoenzyme of nitrate reductase are unlinked. PMID- 24221730 TI - Production of aposporous gametophytes and calli from Pteris vittata L. pinnae strips cultured in vitro. AB - Murashige and Skoog's modified medium in 1% Difco Bacto-agar supplemented with sugar alcohols (sorbsitol, mannitol), growth regulators (1-naphthalenacetic acid, 2,4-dichlorophenoxyacetic acid, benzyladenine, kinetin) and sugars (fructose, glucose, sucrose) induced aposporous gametophytes from pinnae of Pteris vittata cultured in vitro at lower concentrations of all the mentioned components. Aposporous gametophytes and vegetative calli were produced at higher concentrations. The calli regenerated sporophytes when cultured on MS medium without growth regulators. The gametophytes grew vegetatively on MS medium but produced sporophytes when transferred into 0.1 strength MS medium. This is the first report of simultaneous production of calli and gametophytes from fern explants. PMID- 24221731 TI - Effect of calcium, manganese and lithium on growth and cardenolide content in cell suspension cultures of Digitalis thapsi L. AB - Cell suspension cultures of Digitalis thapsi were grown in Murashige and Skoog medium under continuous light. The effects of the absence of CaCl2, elevation of the MnSO4 concentration from 0.1 mM to 5 mM or the addition of 100 MUM LiCl on their growth and digoxin production were investigated. The elimination of calcium reduced growth and viability of cultures but promoted digoxin formation. An increase of the MnSO4 concentration or the addition of LiCl resulted in higher digoxin content. Under such conditions growth was not affected. PMID- 24221732 TI - Methodical improvements in rye anther culture. AB - The crucial problem in anther culture of rye (Secale cereale L.) is the very low regeneration capacity. Our study was conducted to overcome this restriction. The plant material used included a doubled haploid line (DH), two single crosses between DH Unes, and a tetraploid Secale cereale L. population. The factors carbohydrate source, post-plating temperature treatment, and gelling agent were investigated. Substantial progress was achieved by substituting maltose for sucrose. Top rates of 49 % responding anthers and 20 % green plants were obtained from one of the single crosses after a post-plating cold treatment on geirrte solidified medium. We consider our results a methodical step forward in rye anther culture. PMID- 24221733 TI - An internal standard improves the reliability of transient expression studies in plant protoplasts. AB - Transient expression of foreign genes introduced on a plasmid into isolated plant protoplasts is widely used to study the control of gene expression. Unfortunately, many experimental variables implicated in this technique are difficult or impossible to control, resulting in a disturbing degree of variability between otherwise identical experiments. We have studied the co expression of two constitutively expressed genes located on the same plasmid. This has allowed us to identify the lot of plasmid DNA as an important source of variation, along with the protoplast lot. Plasmid DNA concentration was found to be of minor importance. Since the variation of expression level of the two genes was identical for the two genes in all experiments, we propose the use of an internal standard in all comparative transient expression studies, which allows the reduction of the variation between experiments by one order of magnitude. PMID- 24221734 TI - Influence of agar gel properties on the in vitro micropropagation of different clones of Thuja plicata. AB - The influence of four agar-type polysaccharides, used as solidifying agents for culture media and differing in their sulfate content (0.14 to 10.95 % w/w), was tested on the budding and the elongation of five clones of Thuja plicata. Budding is reduced on the most sulfated polysaccharide and the differences observed between clones in elongation are as important as those observed between agar types. PMID- 24221735 TI - Accumulation of the sesquiterpenes nootkatone and valencene by callus cultures of Citrus paradisi, Citrus limonia and Citrus aurantium. AB - The production of the sesquiterpenes nootkatone and valencene by callus cultures of Citrus species is described. The levels of these compounds were examined by gas chromatography-mass spectrometry and their yields were compared with the amounts found in mature fruits. A simultaneous increase and decrease in the levels of nootkatone and valencene, respectively, were observed with the aging of callus cultures of Citrus paradisi. These results suggest that valencene might be a possible precursor of nootkatone in this species. The high level of nootkatone detected in 9-month-old callus cultures of Citrus paradisi might be associated with the corresponding cell morphological changes observed. PMID- 24221736 TI - In vitro plant regeneration from cotyledon and hypocotyl segments in two bell pepper cultivars. AB - In vitro plant regeneration has been obtained from Capsicum annuum cvs. Pico and Piquillo. Shootbuds were induced from hypocotyl and cotyledon segments after 15 20 days of culture on MS basal medium supplemented with IAA and BAP or Zeatin. Shoot-buds grew into rosettes that rooted in MS plus NAA (0.1 mg/l) and IBA (0.05 mg/l) after 15 days. The small plantlets were successfully transferred to pots with a mixture of peat and perlite and maintained under greenhouse conditions. Elongation took place when the plantlets were growing in the greenhouse. PMID- 24221737 TI - Plant regeneration from callus-derived protoplasts of Pelargonium x domesticum. AB - A protocol for regenerating plants from callus-derived protoplasts of Pelargonium x domesticum (rega l geranium cv. 'Melissa') has been developed. Protoplasts were isolated from leaf-derived callus tissue on MS medium supplemented with 3.0 mg/l naphthalene acetic acid, 2.0 mg/l 6- benzylaminopurine, and 3.0% sucrose. This callus yielded 2.7*10(5) protoplasts/gram of tissue after a 6 hr incubation in an enzyme solution consisting of 2.0% cellulysin, 0.5% macerase, and 0.5 M sucrose. Protoplasts were plated at 1*10(5) protoplasts/ml in a mixture (1?1 v/v) of KMP8/KP liquid medium layered on the same medium solidified with 0.6% agarose. Protoplast division was initiated within 2 days, and colonies of 15 to 50 cells developed 8 wk after plating. P-calli 1-2 mm(3) developed 15 wk after plating, and plants regenerated from the p-calli have been transferred to the greenhouse. PMID- 24221738 TI - The influence of phytohormones on growth, organ differentiation and fructan production in callus of Symphytum officinale L. AB - Callus derived from Symphytum officinale L. regenerants was cultured in the presence of various phytohormones. The growth rate of callus was stimulated by all phytohormones at various concentrations. With 1-naphthaleneacetic acid no organ differentiation could be observed. With indole-3-butyric acid at low concentrations only roots were formed, whereas 6-benzylaminopurine, kinetin and zeatin at various concentrations induced either root or shoot formation or the simultaneous regeneration of both. Minor amounts of fructans were formed at high 6-benzylaminopurine-, zeatin- and at all indole-3-acetic acid-concentrations. The concentration of 1-naphthaleneacetic acid had no influence on the fructan content. Highest rates of fructan synthesis occurred at low zeatin-concentrations up to 1.5 mg/l. Only zeatin at all concentrations induced the synthesis of polyfructans, whereas appreciable amounts of oligofructans were formed under the influence of all other phytohormones. PMID- 24221739 TI - Evaluation of somaclonal variation during somatic embryogenesis of interior spruce (Picea glauca engelmannii complex) using culture morphology and isozyme analysis. AB - Somaclonal variation during interior spruce (Picea glauca engelmannii complex) somatic embryogenesis was evaluated using culture morphology and isozyme analysis. Genotype-specific abscisic acid-dependent developmental profiles and isozyme patterns were similar for subclone and parent line embryogenic cultures and cotyledonary somatic embryos. Extensive analysis of fifteen hundred subclone embryos of one genotype revealed no isozyme pattern variation. Initiation of embryogenic cultures was dependent on the developmental stage of the explant although cultures derived from different stages were morphologically similar. The embryogenic cultures initiated from interior spruce embryos show a high degree of genetic stability in that the morphological behavior and isozyme phenotype were always consistent with that of the explant genotype. These results support the conclusion that this culture system is appropriate for clonal propagation of interior spruce. PMID- 24221740 TI - Reduced intracellular content of methotrexate in an isolated MTX-resistant cell line of Nicotiana plumbaginifolia. PMID- 24221741 TI - Evaluation of lime requirement tests for minesoils. AB - Evaluation of twelve minesoils collected from restored or abandoned surface mines in eastern Kentucky with six standard lime requirement procedures showed that one of the procedures accurately forecasted long term lime requirements. The minesoils were then evaluated for potassium choloride-extractable aluminum using the Yang exchangeable acidity procedure. When the extractable A1(3+) was multiplied by a factor of 2.24 it was found to also be an accurate measure for longterm limestone requirements. To bring the minesoil to pH 5.5 the results obtained using the modified Yuan procedure indicate that for each MEQ Al(3+) extracted per 100 grams of minesoil 2.24 Mg of calcium carbonate (CaCO3) equivalent lime per hectare be applied. Application of lime based on this procedure and one of the standard lime procedures resulted in pH stability of the minesoils for forty months. PMID- 24221742 TI - Evaluation procedures for restored land. AB - Release of land for mineral extraction is often dependent on the quality of the restoration which can be achieved. It follows, therefore, that some means of judging the success of restoration is required, especially where restoration is an agricultural after use.In order to assess whether land has been well restored it is therefore necessary to know what the physical characteristics of the land were before mineral extraction took place, what changes are likely to have occurred to the land and soil as a result of mineral extraction, and lastly whether the physical characteristics of the land are as good as when the land was last used for agriculture. Most permissions however, were granted before there was a requirement to record pre-site conditions so it is impossible to know what the site was like when it was last used for agriculture. Furthermore, this paper will argue that land quality is only one factor which should be considered in assessing the quality of restored land, other factors for example, visual integration, farm management must also be taken into consideration. This paper will outline the existing evaluation procedures used by the Ministry of Agriculture, Fisheries & Food and Minerals Planners and suggest developing an evaluation procedure which considers various dimensions of restored land namely soil and land quality, visual integration and the management and productivity of restored land. This evaluation procedure has been applied to seventeen study sites of sand and gravel pits. The paper will indicate whether the evaluation procedure successfully classified these sites or not. PMID- 24221743 TI - Arsenic management in shale oil upgrading. AB - Although the timing remains uncertain, the production of synthetic crude from oil shale seems to be a likely response to diminishing petroleum reserves. Although not unique to shale oil, the presence of arsenic, ranging in concentration from a few to over 100 parts per million, poses a special concern.Arsenic is typically removed from the shale oil by a hydro-processing technique and is concentrated on a catalyst as thermally stable metal arsenides and metal arsenous sulfides. Because this arsenic is still slightly soluble in water, making the spent catalyst a hazardous material, passivation and extraction techniques were investigated to make the catalyst safe for disposal. Passivation techniques were not successful. While extraction procedures were capable of removing over 75% of the arsenic, treated material may still be acceptable. PMID- 24221744 TI - Coal rejects - a wasted resource? AB - The paper outlines potential uses for coal washery rejects. It considers in detail the use of fluidized-bed combustion as a means of lessening rejects disposal problems, as a method of recovering energy for drying, steam raising and electricity production and as a source of ash as a substitute for natural aggregate. Considerable technical information is now available on the use of fluidized beds for these purposes and the paper concludes that it is appropriate to consider a more detailed, site-specific, evaluation. PMID- 24221745 TI - Cyanide effluent control by freeze/thaw processing. AB - With many northern gold mining operations the disposal of waste water from the process presents some unique problems. The level of heavy metals and cyanide is generally too high to allow discharge to the environment. Total impoundment of the effluent in tailing dams or the use of expensive treatment plants is necessary to ensure protection of the environment. The costs and dangers of these treatment methods cannot always be justified in the remote locations of these mines and alternatives must be explored.In this paper, experiments have been performed to determine the partial freezing and melting characteristics of cyanide solutions as well as the rates of natural degradation. These studies could result in a novel method to protect our northern environments and ensure the continued operation of gold mines in these regions in a safe and economic manner. A multi-pond containment system has been proposed which may be feasible in certain circumstances. PMID- 24221746 TI - Clinical studies examining the impact of obesity on breast cancer risk and prognosis. AB - Obesity is associated with an increased risk of breast cancer, and increased risk of recurrence in women who develop breast cancer. Evidence suggests that the risk of estrogen-receptor (ER)-positive breast cancer is increased in obese postmenopausal women, whereas in premenopausal women the risk of triple negative breast cancer is increased. Nonetheless, the presence of obesity at diagnosis, and possibly weight gain after diagnosis, may independently contribute to an individual's risk of recurrence of both pre- and postmenopausal breast cancer. Factors associated with adiposity that are likely contributing factors include hyperinsulinemia, inflammation, and relative hyperestrogenemia. Some studies suggest that some aromatase inhibitors may be less effective in obese women than lean women. Clinical trials have evaluated pharmacologic (eg, metformin) and dietary/lifestyle interventions to reduce breast cancer recurrence, although these interventions have not been tested in obese women who may be most likely to benefit from them. Further research is required in order to identify adiposity associated factors driving recurrence, and design clinical trials to specifically test interventions in obese women at highest risk of recurrence. PMID- 24221748 TI - Preface. PMID- 24221749 TI - Roots of fish endocrinology, a perspective. PMID- 24221747 TI - Biology of glucose transport in the mammary gland. AB - Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells during lactation. Glucose is taken up by mammary epithelial cells through a passive, facilitative process, which is driven by the downward glucose concentration gradient across the plasma membrane. This process is mediated by facilitative glucose transporters (GLUTs), of which there are 14 known isoforms. Mammary glands mainly express GLUT1 and GLUT8, and GLUT1 is the predominant isoform with a Km of ~10 mM and transport activity for mannose and galactose in addition to glucose. Mammary glucose transport activity increases dramatically from the virgin state to the lactation state, with a concomitant increase in GLUT expression. The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in mammary epithelial cells during lactogenesis. In addition to its primary presence on the plasma membrane, GLUT1 is also expressed on the Golgi membrane of mammary epithelial cells and is likely involved in facilitating the uptake of glucose and galactose to the site of lactose synthesis. Because lactose synthesis dictates milk volume, regulation of GLUT expression and trafficking represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up regulated in breast cancer cells to accommodate the increased glucose need. PMID- 24221750 TI - The tilapia prolactin cell: A model for stimulus-secretion coupling. AB - The tilapia prolactin (PRL) cell responds rapidly (10-20 min) to small physiological changes in medium osmotic pressure (OP), releasing increasing quantities of hormone as medium OP is reduced. This release is rapidly (<= 10 min) inhibited by somatostatin (SRIF). There is now extensive evidence that tilapia PRL cell function is regulated through the second messengers Ca(++) and cAMP. Our studies have shown that PRL release is augmented by treatments that lead to increased levels of intracellular Ca(++) or cAMP. On the other hand, PRL release is blocked when tissues are incubated in Ca(++)-depleted medium or upon the addition of Co(++), an inhibitor of Ca(++)-mediated processes. The use of(45)Ca(++) to characterize the movement of Ca(++) into PRL cells has provided evidence that an increase in the influx of extracellular Ca(++) may participate in PRL release upon exposure to hyposmotic medium. Our studies have also shown that SRIF suppresses the increase in(45)Ca(++) accumulation that is brought about when OP is reduced. We have also examined the effects of OP and SRIF on cAMP levels. The reduction of medium OP did not alter cAMP metabolism during 20 min of incubation. By contrast, cAMP accumulation in the presence of IBMX was enhanced at 1 hr of incubation in reduced OP. Thus, an increase in cAMP turnover may play a role in maintaining PRL release under sustained stimulation. SRIF reduced the accumulation of cAMP during 10 min of incubation with IBMX and also reduced the forskolin-stimulated increase in cAMP. Thus, SRIF may suppress adenylate cyclase activity. Finally, our studies have revealed that the forskolin-stimulated increase in cAMP levels is not dependent upon medium Ca(++). The presence of Ca(++) in the medium is required, however, for PRL release even when the cAMP messenger system has been activated. Moreover, cAMP accumulation was augmented when intracellular Ca(++) was increased. This raises the possibility that reduced OP may stimulate an increase in cAMP turnover indirectly through its action(s) on cytosolic Ca(++). PMID- 24221751 TI - Neuropeptides regulating the activity of goldfish corticotropes and melanotropes. AB - The goldfish (Carassius auratus) has proven an advantageous model for investigations of the neuroendocrine regulation of pituitary hormone secretion in teleost fishes. Investigations examining the secretion of adrenocorticotropin (ACTH) and melanocyte-stimulating hormone (MSH) from pituitary cellsin vitro have been used to identify neuropeptides influencing goldfish corticotrope and melanotrope activity. Ovine CRF, urotensin I (UI), arginine vasotocin (AVT), isotocin and angiotensins I and II stimulate the release of ACTH from corticotropesin vitro. Thyrotropin-releasing hormone (TRH), oCRF, UI and neuropeptide Y stimulate the release of MSH from melanotropesin vitro. Immunocytochemical studies have revealed the presence of separate CRF- and UI immunoreactive perikarya in the hypothalamus suggesting the existence of two structurally similar, yet distinct, hypothalamic CRF-UI-like peptides. Interactions of AVT and CRF in the regulation of ACTH secretion is suggested from studies demonstrating the co-localization of AVT- and CRF-immunoreactivities in perikarya of the preoptic-hypophyseal system. These investigations demonstrate that the secretory activity of goldfish corticotropes and melanotropes is influenced by a diversity of neuropeptides of hypothalamic origin. PMID- 24221752 TI - The duality of teleost gonadotropins. AB - The duality of salmon gonadotropins has been proved by biochemical, biological, and immunological characterization of two chemically distinc gonadotropins. GTH I and GTH II were equipotent in stimulating estradiol production, whereas GTH II appears to be more potent in stimulating maturational steroid synthesis. The ratio of plasma levels and pituitary contents of GTHs and the secretory control by a GnRH suggest that GTH I is the predominant GTH during vitellogenesis and early stages of spermatogenesis in salmonids, whereas GTH II is predominant at the time of spermiation and ovulation. GTH I and GTH II are found in distinctly separate cells. In trout, GTH I is expressed first in ontogeny, whereas GTH II cells appear coincident with the onset of spermatogenesis and vitellogenesis, and increase dramatically at the time of final reproductive maturation. Comparison of the amino acid sequences of polypeptides and the base sequences of cDNA revealed that salmon GTH I beta is more similar to bovine FSHbeta than bovine LHbeta and salmon GTH II beta shows higher homology to bovine LHbeta than to bovine FSHbeta. The existence of two pituitary gonadotropins in teleosts as well as tetrapods suggests that the divergence of the GTH gene took place earlier than the time of divergence of teleosts from the main line of evolution leading to tetrapods. PMID- 24221753 TI - Physiology of fish endocrine pancreas. AB - From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined. PMID- 24221754 TI - Endocrinology and fish culture. AB - In the current practice of fish culture the use of hormones is mainly limited to the field of reproduction, and more precisely to induce or synchronize ovulation and stimulate spermiation. The practice of pituitary homogenates injection (called hypophysation) which started in the early 1930's has allowed spectacular developments in the culture of some cyprinid species, especially in China, India and Europe. HCG has been used successfully in a limited number of species and LHRH-A, often associated with antidopaminergic compounds, started to be used in some species, especially cyprinids, on a commercial scale. Sex steroids are now commonly used to reverse the sex of some species in salmonids, cyprinids, tilapias. Due to legal restriction and consumer opposition, the tendency is to limit the use of steroids, especially in fish which are later offered to consumption. GH, which significantly stimulates growth and reduces the food conversion rate in laboratory experiments, will possibly be used on a large scale in fish farms. Endocrinology has considerably increased the knowledge of the mechanisms controlling some physiological functions; this has allowed the identification of sensitive phases in fish in captivity, and helps in the management and the process of domestication (most of the cultured fish species have been taken form the wild recently). PMID- 24221755 TI - The bioactivity of gonadotropin releasing hormones and its regulation in the gilthead seabream,Sparus aurata: in vivo andin vitro studies. AB - Thein vivo andin vitro potency of native and modified forms of gonadotropin releasing hormone (GnRH) to release gonadotropin (GtH) was studied inSparus aurata and correlated with their relative susceptibility to degradation by cytosolic-bound enzymes of the pituitary, kidney, and liver. Salmon (s) GnRH and luteinizing hormone-releasing hormone (LHRH) are equipotent whereas analogs of these peptides ((D-Arg(6)-Pro(9)NET)-sGnRH, (D-Ala(6)-Pro(9)NET)-LHRH, (D-Trp(6)) LHRH) are superactive in inducingin vivo GtH release (at 10 ug/kg body weight). In anin vitro superfusion system of pituitary fragments all analogs are equipotent to the native peptides (at 10(-10) to 2.5 * 10(-7)M). sGnRH and LHRH are rapidly degraded by cytosolic peptidases of the pituitary, liver, and kidney. The preferred site of cleavage is the Tyr(5)-Gly(6) bond. Substitution of the position 6 glycine by D-amino acids renders the 5-6 bond resistant to degradation and shifts the main site of cleavage to the Pro(9)-Gly(10)NH2 bond. Substitution at position 6 (as above) and at position 10 with Pro(9)NET results in analogs that are resistant to degradation. We propose that enzymatic cleavage terminates GnRH bioactivityin vivo and thus increased resistance to degradation is a major determinant of GnRH analog superactivity. PMID- 24221756 TI - Characterization, cerebral distribution and gonadotropin release activity of neuropeptide Y (NPY) in the goldfish. AB - The presence of a peptide closely related to porcine NPY has been demonstrated in the goldfish brain and pituitary by means of radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). The RIA data demonstrate that displacement curves of brain extracts are parallel to a porcine NPY standard and that in HPLC a compound present in brain extracts is co-eluted with porcine NPY. The distribution of this NPY-like factor within the central nervous system was studied by radioimmunoassay and immunohistochemistry. The results indicated that NPY has a widespread distribution with the highest concentrations being found in the telencephalon and diencephalon. In the pituitary gland, NPY immunoreactive terminals characterized at the electron microscope level were found in the different lobes and, in particular, in close association with the gonadotrophin (GTH) secreting cells. Using anin vitro perifusion system, it was shown that NPY causes a dose dependent increase of GTH release from anterior lobe fragments.These data indicate for the first time in teleosts that NPY is present and widely distributed in the brain and pituitary, and that among other putative functions, could be implicated in the multihormonal release of GTH from the pituitary. PMID- 24221757 TI - Neuropeptide Y (NPY) modulatesin vitro gonadotropin in release from rainbow trout pituitary glands. AB - This work investigated the action of neuropeptide Y (NPY) on thein vitro pituitary release of the maturing gonadotropic hormone (GtH) of the rainbow trout using a perifusion system employing trout balanced salt solution (pH 7.5) at 15 degrees C and a 12.5 ml/h flow rate. In vitellogenic females a 20 minutes NPY application (10(-7) M) induced a 20-30% decrease in GtH secretion. Removal of NPY was followed by a rebound in GTH secretion. On the contrary, in ovulated females, NPY (15 minutes, 10(-7) M) directly stimulated GTH secretion. The greatest stimulation was obtained the day of ovulation where the stimulatory effect of NPY was similar to those induced by s.GnRH in the same conditions, reaching 400% of the basal GTH level. In vitellogenic females treated with 1-4-6 androstadien 3-7 dione, an inhibitor of aromatase activity, the pituitary response to NPY was similar to that obtained in ovulated females. Thus thein vitro action of NPY might depend on thein vivo steroidogenic environment. PMID- 24221758 TI - The origin of the mammalian form of GnRH in primitive fishes. AB - The presence of neuroendocrine hormones in extant agnathan fishes suggests that a method of control involving these hormones was operating 500-600 million years ago in emerging vertebrates. Data on a limited number of species show that several members of the GnRH family of peptides may have arisen in non-teleost fishes. Lamprey (Petromyzon marinus) GnRH has a unique composition and has not been detected in other vertebrates. It is not yet clear whether the chicken II GnRH-like molecule arose in cartilaginous fishes, but a chromatographically and immunologically similar molecule is found in dogfish (Squalus acanthias) and ratfish (Hydrolagus colliei). Finally, a mammalian GnRH-like molecule is detected in three primitive bony fish: sturgeon (Acipenser transmontanus), reed fish (Calamoichthys calabaricus), and alligator gar (Lepidosteus spatula). Minor forms are also present, but are not yet characterized. Clearly, the basic structure of GnRH peptides was established in primitive fish. In contrast, at least three other identified forms of GnRH have been detected in teleosts or tetrapods: Salmon I, catfish I, and chicken I GnRH. Evidence for the presence of members of the GnRH family and the neurohypophysial hormone family in primitive fishes argues for the importance of neuroendocrine control throughout the history of vertebrates. PMID- 24221759 TI - Monoaminergic substances in the teleost brain: Catecholamine levels in male and female winter flounder,Pseudopleuronectes americanus Walbaum, associated with gonadal recrudescence. AB - High performance liquid chromatography with electrochemical detection (HPLC-EC) was used to quantitate catecholamine (CA) levels in the winter flounder brain following perchloric acid extraction/alumina purification of CNS tissues. Greater concentrations of norepinephrine (NE) and dopamine (DA) were present in the hypothalamus compared with the CA levels in whole brain. A seasonal study of CA brain levels in reproductively active male and female flounder demonstrated that monoamine levels reach their maxima in October in association with the rapid increases in gonadosomatic index. When perchloric acid extracts of the teleost and rat hypothalamus were submitted to direct HPLC-EC analysis, without alumina purification of CA neurotransmitters, similar hypothalamic profiles were obtained indicating the presence of identifiable biogenic amine neurotransmitters substances including NE, DA and serotonin (5-HT). PMID- 24221760 TI - Effects of lamprey gonadotropin-releasing hormone and analogs on steroidogenesis and spermiation in male sea lampreys. AB - The biological activities of lamprey GnRH and analogs were determined in the adult male lamprey,Petromyzon marinus. Two successive injections of lamprey GnRH at 0.005, 0.065 or 0.163 MUg/g body weight or [D-Ala(6),Pro(9)-NHEt] mammal GnRH at 0.05 MUg/g stimulated plasma estradiol and progesterone levels in adult male lampreys undergoing final maturation. In these experiments, a lamprey GnRH putative antagonist, [D-Phe(2,6),Pro(3)] lamprey GnRH, at 0.075, 0.150 or 0.3 MUg/g stimulated plasma estradiol but not progesterone levels. Four successive injections of lamprey GnRH at 0.05 or 0.1 MUg/g stimulated plasma progesterone and spermiation. [D-Phe(2,6),Pro(3)] lamprey GnRH at 0.05 or 0.1 MUg/g depressed plasma progesterone levels and inhibited spermiation. In contrast, lamprey GnRH analog, [D-Ala(6),Pro(9)-OH free carboxylic acid] lamprey GnRH, at 0.05 or 0.1 MUg/g stimulated plasma progesterone levels and inhibited spermiation. In summary, lamprey GnRH is biologically active in stimulating the pituitary-gonadal axis in adult male lampreys as determined by steroidogenesis and spermiation. PMID- 24221761 TI - Pituitary gonadotropin-releasing hormone (GnRH) receptor activity in goldfish and catfish: seasonal and gonadal effects. AB - The goldfish pituitary contains two classes of gonadotropin-releasing hormone (GnRH) binding sites, a high affinity/low capacity site and a low affinity/high capacity site (Habibiet al. 1987a), whereas the catfish pituitary contains a single class of high affinity GnRH binding sites (De Leeuwet al. 1988a). Seasonal variations in pituitary GnRH receptor binding parameters, and the effect of castration on pituitary GnRH receptor binding were investigated in goldfish and catfish, respectively. In goldfish, GnRH receptors undergo seasonal variation with the highest pituitary content of both high and low affinity sites occurring during the late stages of gonadal recrudescence. The observed changes in pituitary GnRH receptor content correlate closely with responsiveness to a GnRH agonistin vivo in terms of serum gonadotropin (GTH) levels. In catfish, castration results in a two-fold increase in pituitary GnRH receptor content, which can be reversed by concomitant treatment with androstenedione, but not by the non-aromatizable androgen 11beta-hydroxyandrostenedione; changes observed in GnRH receptor content correlate with variations in serum GTH levels and responsiveness to a GnRH agonist. In summary, the present study provides a clear evidence for seasonal variation in pituitary GnRH receptor activity in goldfish, and demonstrates a gonadal feedback mechanism regulating GnRH receptor activity in the catfish pituitary. PMID- 24221762 TI - Unequal activities of the two tilapia prolactins in the whole-animal transepithelial potential bioassay using the red eft. AB - The cichlid fish tilapia (Oreochromis mossambicus) produces two forms of prolactin (tPRL177 and tPRL188) at equal rates. The primary sequences of this prolactin pair share only 69% identity. In these experiments, the whole-animal transepithelial potential (TEP) in the eft stage of the red-spotted newt (Notophthalmus viridescens) was measured in response to two injections totaling about 2 MUg of tPRL177, tPRL188, ovine PRL, or tilapia growth hormone (tGH), or distilled water (5 MUL/injection). This investigation was undertaken in order to locate prolactin receptors which discriminate between the two molecular forms of tilapia prolactin. The salamandrid integumental bioassay for prolactin was found to respond to tPRL177 as it does to ovine PRL. The more mainline tPRL188 was without effect at this dose and thus behaved more similarly to growth hormone (tilapia and ungulate) in this bioassay. The suspected magnitude of differences in the molecular surface characteristics between the two prolactins seem to be adequate to allow the binding of tPRL177 and to hinder the binding of tPRL188 to prolactin specific receptors in eft epithelial tissues. PMID- 24221763 TI - Morphogenesis and distribution of the endocrine pancreas in adult lampreys. AB - The endocrine pancreas of larval lampreys appears as islets of cells isolated in the submucosa and those both continuous with, and within, the gut epithelium at the intestinal-oesophageal-bile duct junction. The islets, and occasionally follicles, are composed of only insulin-secreting (B) cells. During metamorphosis, the bile duct either completely degenerates or its epithelium transforms into a caudal endocrine pancreas while a cranial pancreas appears as a specialization and expansion of the larval pancreas. Immunocytochemistry and histochemistry demonstrates that there is a wide variation in the distribution of the pancreatic tissue in adults of lamprey species, and this variation may result from interspecific differences in morphogenetic events at metamorphosis. Despite species variability in its distribution, the endocrine pancreatic tissue in all adult lampreys is composed of equal numbers of B cells and somatostatin-secreting (D) cells, but there are no glucagon-secreting (A) cells. Immunocytochemistry reveals that B and D cells of the caudal pancreas differentiate from cells of the larval bile duct during metamorphosis of the sea lamprey,Petromyzon marinus. PMID- 24221764 TI - Hypothalamic peptides influencing growth hormone secretion in the goldfish,Carassius auratus. AB - In vivo andin vitro techniques were used to examine the influence of various vertebrate peptides on growth hormone (GH) secretion in the goldfish. Tetradecapeptide somatostatin (SRIF-14) was found to inhibit GH secretionin vitro from perifused pituitary fragments, whereas similar concentrations of a salmonid SRIF peptide (sSRIF-25) did not affect GH secretion from the goldfish pituitary fragments. This indicates that SRIF receptors on the goldfish pituitary are very specific for SRIF-14-like peptides. Salmon gonadotropin (GTH)-releasing hormone (sGnRH) was found to elevate serum GH levels in male goldfish. The dopamine antagonist pimozide alone or injected in combination with sGnRH did not influence serum GH levels, although injection of pimozide alone significantly elevated serum GTH levels, in addition to potentiating the effects of sGnRH on GTH secretion. sGnRH stimulated GH secretion from goldfish pituitary fragmentsin vitro, indicating that sGnRH acts directly at the level of the pituitary to stimulate GH secretion in the goldfish. These results suggest that GnRH may also function as a GH-releasing factor in the goldfish, although the release inhibitory factors for GH and GTH secretion do appear to be separate and distinct. Two human GH-releasing hormone (hGHRH) peptides were found to be ineffective in altering GH secretionin vitro from the perifused pituitary fragments. Consequently, a role for a mammalian GHRH-like peptide in the hypothalamic regulation of GH secretion in the goldfish remains questionable. PMID- 24221765 TI - Involvement of steroid hormones in the preovulatory gonadotropin surge in female goldfish. AB - Goldfish,Carassius auratus, spawn several times within a spawning season. A gonadotropin (GtH) surge occurs at the time of ovulation in this cyprinid species. This ovulatory GtH surge mediates the processes of final oocyte maturation and ovulation, and occurs at the end of each spawning cycle. Within a cycle, there is a shift in the predominant plasma steroid from estradiol to testosterone, and finally 17alpha, 20beta-dihydroxy-4-pregnen-3-one at the time of the ovulatory GtH surge. High levels of testosterone were always observed before ovulation. When ovariectomized or sexually regressed female goldfish were implanted with testosterone, they exhibited a GtH surge which was similar to those normally observed at ovulation. These results strongly suggest that elevated plasma testosterone is an important physiological requirement for the occurrence of the GtH surge. PMID- 24221766 TI - Relationship between metabolic and reproductive hormones in salmonid fish. AB - Circulating concentrations of estradiol (E2), vitellogenin (VTG), thyroxine (T4), triiodothyronine (T3) and insulin were measured in reproductively maturing four and five year-old Atlantic salmon. Blood samples were collected from the fish in seawater for one year prior to their spawning in November in fresh water. In females, E2 and VTG were low but detectable from December to July, and then increased to peak levels in September and October. Plasma levels of T4 and T3 were relatively constant in winter and spring, and decreased in July. Plasma concentration of T4 increased in November when the fish returned to fresh water. Plasma T3 levels remained low during the autumn. Both T4 and T3 levels tended to be higher in males than in females during September through November. Plasma insulin concentrations increased during the spring to peak values in May, and then decreased in June and July in fish of both sexes. There was a significant elevation of plasma insulin in males during October, and the levels in males tended to be higher than those found in females during final maturation. PMID- 24221767 TI - Positive feedback control by the gonads on gonadotropin (GTH) and gonadoliberin (GnRH) levels in experimentally matured female silver eels,Anguilla anguilla. AB - Treatment of sham-operated female silver eels with carp pituitary extract stimulated ovarian development and induced increases in pituitary gonadotropin (GTH) and gonadoliberin (GnRH) contents. Both effects of carp pituitary extract were abolished in ovariectomized eels, indicating the involvement of the gonads. Endogenous sexual steroids, the secretion of which was increased during sexual maturation, should be responsible for the stimulation of GTH and GnRH levels. Ovariectomy itself had no significant effect on pituitary GTH and GnRH contents, reflecting the fact that, at the silver stage, sexual steroid levels are too low to exert any significant effect on pituitary GTH and GnRH. The positive feedback control exerted by the gonads on GTH and GnRH levels during sexual maturation, in the eel as well as in some other teleosts, would produce an amplification of the pubertal stimulation of the hypothalamo-pituitary-gonadal axis. PMID- 24221768 TI - The role of prostaglandins in the control of ovulation in yellow perch,Perca flavescens. AB - Previous studies have shown that 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P) can induce both germinal vesicle breakdown and ovulationin vitro of yellow perch (Perca flavescens) oocytes. The stimulation of ovulation can be blocked by indomethacin and restored by the subsequent addition of several primary prostaglandins (Goetz and Theofan 1979).In the present investigation, medium levels of prostaglandin F (PGF) and E (PGE) were measured by radioimmunoassay duringin vitro 17alpha,20beta-P-induced ovulation of perch oocytes. PGF levels increased significantly (compared to controls) from 30 to 36h of incubation. Hourly samples taken through the time of ovulation revealed that the increase in PGF was very closely correlated to the time of ovulation though it did not preceed it. Cortisol, testosterone, estradiol-17beta, 17alpha,20alpha dihydroxy-4-pregnen-3-one and 17alpha-hydorxyprogesterone did not increase PGF levels by 48h of incubation, however, several other progestational steroids including 20beta-dihydroprogesterone (20beta-P) and progesterone did. 17alpha,20beta-P, 20beta-P and progesterone also stimulated an increase in PGF in spontaneously ovulating oocytes (in which all oocytes ovulated including controls), indicating that the increase in PGF was not merely a result of the physical process of ovulation but was related to the presence of the steroid. PMID- 24221769 TI - Gonadotropins I and II in juvenile coho salmon. AB - The present study was designed to obtain basic endocrine information on GTH I and GTH II in previtellogenic and prespermatogenic coho salmon (immature). Levels of GTH II in pituitary extracts were 6.5 +/- 2.0 and 6.7 +/- 2.0 pg/MUg pituitary protein in male and female fish, respectively. In contrast, the pituitary content of GTH I was approximately 100-fold higher than GTH II (1.302 +/- .22 and 1.173 +/- .21 ng/MUg pituitary protein in male and female fish, respectively). Plasma levels of GTH II in immature salmon were not detectable by RIA whereas plasma GTH I levels were approximately 0.62 +/- 0.12 and 0.78 +/- 0.13 ng/ml in male and female fish, respectively. Highly purified coho salmon GTH I and GTH II stimulated testicular testosterone production and ovarian estradiol productionin vitro in a similar manner, though GTH II appeared more potent than GTH I. Therefore, it appears that although the salmon pituitary contains predominantly GTH I prior to puberty, the gonad can respond to both GTH I and GTH II. PMID- 24221770 TI - Isolation of pituitary glycoprotein gonadotropins from the grass carp (Ctenopharyngodon idell). AB - Gonadotropins (GTH) were isolated from pituitary glands of grass carp and their properties investigated. Acetone-dried pituitaries were extracted with ammonium acetate-ethanol and were then passed through cation exchanger, anion exchanger, and gel filtration column. Two glycoprotein gonadotropins (DE I and DE II) were isolated of MW 56,000 and 53,000 daltons, respectively, as determined by gel filtration technique. Isoelectric points of the two GTHs also differed from each other. Sialic acid contents were 3.64% and 1.47% for DE I and DE II, respectively. Both GTH's stimulated, in a similar manner, testicular androgen and ovarian estradiol synthesisin vitro. PMID- 24221771 TI - Evidence that 17alpha,20beta,21-trihydroxy-4-pregnen-3-one is a maturation inducing steroid in spotted seatrout. AB - Ovarian steroidogenesis during final oocyte maturation (FOM) in the spotted seatrout (Cynoscion nebulosus) was investigated by incubating ovarian fragments with tritiated pregnenolone, followed by chromatographic separation of the radioactive products. The major tritiated steroid produced during FOM comigrated with 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20beta-dihydro-11 deoxycortisol, 20beta-S) on HPLC and TLC. Only minor amounts of radioactive material coeluted with 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta P), 11-deoxycorticosterone (DOC), estradiol-17beta and testosterone standards in the HPLC system. Additional chromatography by TLC confirmed the presence of radioactive estradiol-17beta and testosterone but not 17alpha,20beta-P and DOC.All the ovarian steroids producedin vitro during FOM were assayed for their ability to induce germinal vesicle breakdown (GVBD) of spotted seatrout oocytes. Twenty grams of ovarian tissue were incubated with human chorionic gonadotropin and exogenous pregnenolone. The steroidal products were purified by HPLC and TLC. Most of the maturation-inducing activity was confined to steroidal material which comigrated in these systems with 20beta-S. This material was active at a concentration of 1 ng steroid/ml medium in the GVBD assay. Smaller amounts of material which coeluted with 11-deoxycortisol, DOC, 17alpha,20beta-P and several minor unidentified fractions induced GVBD at concentrations of 10 ng steroid(s)/ml.The structure-activity relationships of authentic steroids in inducing GVBD of spotted seatrout oocytes was investigated. Hydroxylation at the 17alpha, 20beta or 21 positions increased potency to induce GVBD. Steroids with multiple hydroxyl groups at the 17alpha and 20beta positions (17alpha, 20beta-P) and at the 17alpha, 20beta, and 21 positions (20beta-S) had maximum biological activity in the GVBD bioassay. The results suggest that 20beta-S is a major maturation-inducing steroid in spotted seatrout. PMID- 24221772 TI - Mechanisms of synthesis and action of 17alpha,20beta-dihydroxy-4-pregnen-3-one, a teleost maturation-inducing substance. AB - This article briefly reviews the current status of investigations, mainly based on the amago salmon,Oncorhynchus rhodurus, on the mechanisms of synthesis and action of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-diOHprog). Pituitary gonadotropin is of primary importance in triggering meiotic maturation in teleost oocytes. However, the maturational action of gonadotropin is not direct, but is mediated by the follicular production of maturation-inducing substance (MIS). It is now well established that 17alpha,20beta-diOHprog is the major MIS of salmonids. Production of this steroid occursvia the interaction of two distinct cell layers, the thecal and granulosa cell layers (2-cell type model). The first step of the stimulating effect of gonadotropin in both layers is the receptor-mediated activation of adenylate cyclase and formation of cAMP. Our findings suggest that the major stimulating action of gonadotropin on 17alpha,20beta-diOHprog biosynthesis is due to the stimulation of 17alpha hydroxyprogesterone production by the thecal layer and the selective induction of thede novo synthesis of 20beta-hydroxysteroid dehydrogenase in the granulosa layer. 17alpha,20beta-diOHprog acts at the surface of the oocyte. The early steps following 17alpha,20beta-diOHprog action involve the formation of the major cytoplasmic mediator of this steroid, maturation-promoting factor (MPF). It was shown that goldfish MPF induces meiotic maturation inXenopus oocytes andvice versa. The chemical characterization of fish MPF is important for our understanding of the precise mode of maturational action of 17alpha,20beta diOHprog. PMID- 24221773 TI - Catechol-O-methyltransferase in the brain of the male African catfish,Clarias gariepinus; distribution and significance for the metabolism of catecholestrogens and dopamine. AB - Catechol-O-methyltransferase, involved in the methylation of catechol substrates, was localized in the brain of the male African catfish,Clarias gariepinus, by means of a radiometric assay using [Methyl-(3)H]S-adenosylmethionine as methyldonor and catecholestrone as substrate. Fore- and midbrain were divided into eighteen, 500 MUm thick, transverse sections. With a hollow needle (diameter 1 mm), specific areas of the brain were punched out and assayed. The catechol-O methyltransferase activity was calculated from the amount of radioactive methoxyestrone formed from catecholestrone and expressed in pmol.mg(-1) tissue.h( 1).The enzyme could be demonstrated throughout the brain. Although the enzyme activity did not differ very much between the various brain regions (max. 15.4; min. 7.5 pmol), there were some areas in the brain with a more than average activity,i.e., the lateral telencephalon (10.3 pmol), the nucleus preopticus (13.1 pmol), nucleus lateralis tuberis (11.0 pmol) and nucleus recessus posterioris (12.0 pmol) of the diencephalon, the tectum opticum (15.4 pmol) and torus semicircularis (13.6 pmol) of the mesencephalon, and the caudal cerebellum of the metencephalon (10.8 pmol). The lowest activity was detected in the caudal metencephalon (7.5 pmol).The presence of the enzyme catechol-O-methyltransferase in the brain of the African catfish and the observation that both catecholestrogens and dopamine can be methylated by this enzyme suggest that catecholestrogens can influence the methylation (inactivation) of dopamine. Incubations of forebrain homogenates with dopamine and catecholestrone or catecholestradiol confirmed that both catecholestrogens can inhibit the methylation of dopamine. Lineweaver-burk plots with various concentrations of the catecholestrogens indicated that the inhibition is competitive. Dixon plots from the inhibition studies gave inhibition constants of 1.4 and 0.6 MUM for catecholestrone and catecholestradiol, respectively, indicating that catecholestradiol is a two times stronger inhibitor than catecholestrone.The significance of the inhibition of the methylation of dopamine by the catecholestrogens in the brain is discussed in the light of the negative feedback of gonadal steroids on the central regulation of reproductive processes. PMID- 24221774 TI - Differentiation and development of Leydig cells, and changes of testosterone levels during testicular differentiation in tilapiaOreochromis niloticus. AB - Initial appearance and development of Leydig cells (LCs) during testicular differentiation in tilapia,Oreochromis niloticus, were investigated histologically. In addition, changes of testosterone levels in gonadal tissue and serum were examined by radioimmunoassay. In the gonads of fry at 23-26 days after hatching, initial testicular differentiation was confirmed by the observation of the differentiation of connective tissues into tissues which are characteristic of the adult testis. LCs, which were identified by the ultrastructural features (a moderate number of mitochondria with tubular cristae, well developed smooth endoplasmic reticulum and many free ribosomes) appeared initially at the time of testicular differentiation. LCs increased in number rapidly in the testes of fish at 70 days after hatching. Concomitant with this increase, spermatogonia increased in number. Testosterone was detectable in the fish at 40-50 days after hatching, but levels in tissue and serum were low. Testosterone levels increased gradually in the fish beginning at 70 days after hatching and increased still more at 100-150 days accompanying active spermatogenesis. PMID- 24221775 TI - Role of the sertoli cell in spermatogenesis: TheSqualus testis model. AB - In the dogfish sharkSqualus acanthias different germ cell stages are topographically segregated within the testis. Using this species we have developed methods for the isolation and culture of Sertoli cells from premeiotic, meiotic and post-meiotic stages of spermatogenesis and present preliminary evidence for stage-dependent variations in cell morphology and behavior, thymidine incorporation, protein synthesis and steroidogenesis. The goal of future studies is to determine how maturational changes are regulated in Sertoli cells and, in turn, to elucidate Sertoli cell-germ cell interactions. PMID- 24221776 TI - Sex steroids in intersexual fishes. AB - Studies of thein vitro gonadal steroidogenesis in intersexual fishes, using labelled testosterone as precursor, showed large species variation. The protogynousMonopterus albus produced predominantly 5alpha-reduced metabolites while the protandrousRhabdosargus sarba produced mainly 5beta-reduced products. Both fishes synthesized 11-oxotestosterone; the synthesis of which appeared to mediate mainly through adrenosterone inM. albus butvia 11beta-hydroxytestosterone inR. sarba.When the plasma levels of androstenedione, testosterone, 11 oxotestosterone, 11beta-hydroxytestosterone, estrone and 17beta-estradiol among the male, intersexual and female phase of the same species were compared, available data showed that either there was no obvious difference among the different sexual phases or the differences could be accounted for by the seasonal reproductive activities of the animal.Except for androstenedione, there are no marked changes in plasma testosterone, 11-oxotestosterone, 11beta hydroxytestosterone, estrone and 17beta-estradiol levels in the intersexual phase compared with the female and male, it is unlikely that these classical sex steroids act as a primary trigger of natural sex reversal in these fishes; the role of androstenedione awaits further elucidation. PMID- 24221777 TI - Genetic influences on reproductive system development and function: A review. AB - This paper presents a current view of the genomic and neuroendocrine interaction based on our studies of the reproductive system in the platyfish (Xiphophorus maculatus). It also presents observations from basic research and applied biologists on natural and artificially reared fishes and indicates that there is a direct genetic involvement in the control of spawning, growth rates, size and age at maturation and final body size, similar to that described in platyfish. The past, present and future association of aquaculture and basic science, especially DNA technology, is discussed and potential directions for future research are presented. PMID- 24221778 TI - Purification of chinook salmon (Oncorhynchus tshawytscha) GH for receptor study. AB - A method for the purification of chinook Salmon (Oncorhynchus tshawytscha) GH, which retains its biological activity, is described. The biological activity was investigated with an established radioreceptor assay using liver membranes from pregnant rabbits and bovine GH as standard and labelled hormone. The enrichment of the preparation was checked with electrophoresis (SDS-PAGE). Extraction and further steps were carried out using low molarity alkaline buffer (pH 8-10, M = 100 mM). Three chromatography steps were performed (Concanavalin-A sepharose, Bio gel P60, DEAE). Ion exchange chromatography was performed under isocratic conditions (using a 50 cm column). Two isoforms (sGH1 and sGH2) were isolated. The purification yield is 0.7% compared to lyophilized pituitaries. The molecule is homogeneous in SDS-PAGE. Contamination by prolactin, gonadotrophin and corticotrophin is negligible (< 0.5%). It could be demonstrated that the biological activity of the preparation is maintained since this preparation stimulates the growth of juvenile trout (Salmo gairdneri) and binds specifically (35%) to trout liver membranes. PMID- 24221779 TI - Stress responses and disease resistance in salmonid fish: Effects of chronic elevation of plasma cortisol. AB - Basal levels of plasma cortisol in unstressed salmonid fish are normally in the range 0-5 ng ml(-1). An acute stress such as handling or 1 h confinement caused a temporary elevation of the plasma cortisol levels of both brown trout,Salmo trutta L., and rainbow trout,Salmo gairdneri Richardson, in the range 40-200 ng ml(-1) with a return to basal levels within 24-48 h. The extent of the cortisol elevation in response to an acute stress was dependent upon both the species and strain of trout. Chronic stresses, such as prolonged confinement or crowding, resulted in an elevation of plasma cortisol levels to approximately 10 ng ml(-1). Under these circumstances, blood cortisol levels remained elevated for periods of up to 4 weeks before acclimation finally occurred.It is shown, by means of intraperitoneal implantation of cortisol, that chronic elevation of plasma cortisol levels in the brown trout results in a dose-dependent increase in mortality due to common bacterial and fungal diseases. This effect is apparent at plasma cortisol levels as low as 10 ng ml(-1), levels below those often reported as being representative of 'unstressed' fish. These findings are discussed in relation to the known immunosuppressive effects of corticosteroids in teleost fish. PMID- 24221780 TI - Regulation of the interrenal of fishes: non-classical control mechanisms. AB - The regulation of the interrenal of teleostean fishes is reviewed from the perspective of non-classical control mechanisms and new evidence is presented suggesting gonadotropic control of the interrenal. Cortisol secretion by the interrenal, in addition to regulation by ACTH, appears to be mediated by other hormones. Physiologically relevant, direct control of interrenal function by hydromineral factors is unclear.In vitro experiments with interrenals of coho salmon (Oncorhynchus kisutch) indicate that salmon gonadotropin is extremely corticotropic and both ACTH and gonadotropin stimulate the secretion of large quantities of androstenedione from the interrenal. PMID- 24221781 TI - Effect of acid environments on cortisol and cortisol receptor activity in Atlantic salmon,Salmo salar. AB - The cytosol and nuclear extract of gill tissue obtained from laboratory held Atlantic salmon,Salmo salar manifested saturable cortisol binding of high affinity and low capacity (cytosol: Ka = 0.198 +/- 0.024 * 10(9)/M, Nmax = 116.8 +/- 20.8 fmol/mg protein; nuclear extract: Ka = 0.823 +/- 0.057 * 10(7)/M, Nmax = 1563 +/- 330 fmol/mg protein; n = 4). The cytosol receptor activity displayed high steroid and tissue specificity and a single binding peak at 191,000 Da following gel permeation chromatography.Atlantic salmon exposed for 3 or 8 months to waters from the Medway River (pH about 5.1), the Westfield River (pH about 4.8) and calcium carbonate treated Westfield River (pH about 5.6) showed no gill cytosol receptor activity. Cortisol receptor activity in the gill nuclear extracts from fish in limed Westfield River water in December (3 months) was less than half the activity in the fish treated with Medway River water (p < 0.05) although the plasma cortisol values were not different. In May (8 months), the plasma cortisol of fish in limed water was almost twice that of the fish held in acid Westfield River water (p = 0.058). PMID- 24221782 TI - Circulatory catecholamines in the eel: origins and functions. AB - While the three catecholamines (CAs) dopamine (DA), norepinephrine (NE) and epinephrine (E), are wide-spread in tissues of the American eel (Anguilla rostrata), the bulk of these CAs in the systemic blood originates from chromaffin cells in the wall of the posterior cardinal veins. In addition, the brain and unidentified structures in the opisthonephric kidney also release appreciable quantities of CAs. The functional realms attributed to systematically circulating CAs in teleosts comprise cardiovascular, respiratory, osmoregulatory, metabolic and endocrinotropic actions. In the eel, cardiovascular and respiratory effects are well established. However, we were unable to prove a physiological role of the CAs in osmoregulation. On the other hand, the eel is the only species among five vertebrates of greatly varying phylogenetic position (the others: hagfish, lamprey, rat, human) in which physiological doses of E were hyperglycemic. As in lamprey and rat, DA and NE are released in the eel by physiological doses of E. In addition, DA and NE also release the respective other two CAs. The physiological significance of the catecholaminotropic (CA-tropic) interactions remains to be established; however, the CA-tropic effect of E does not require the presence of the brain or 'preganglionic' nerve cells. In the eel, mild stress causes an immediate 'unorthodox' drop of plasma CAs, while stronger stress is followed by the expected increase of plasma CAs. PMID- 24221783 TI - Metabolic actions of glucagon-family hormones in liver. AB - This review addresses direct and indirect metabolic actions of hormones co encoded in the preproglucagon gene of fishes. Emphasis is placed on a critical analysis of the effects of glucagon and glucagon-like peptide (GLP) and the current knowledge of the respective modes of action is reviewed. In mammals GLPs exert no direct metabolic actions. In fish liver, GLP and glucagon act on similar targets of intermediary metabolism by enhancing flux through glycogenolysis, lipolysis and gluconeogenesis. Increases in substrate oxidation are not uniform. Hormonal activation of glycogen phosphorylase and triglyceride lipase and inhibition of pyruvate kinase are implicated in these actions. Hormone-dependent hyperglycemia, depletion of hepatic glycogen and increases in free fatty acids are noticeablein vivo. Glucagon also activates hepatic amino acid uptake and ammonia excretion.Glucagon actions are accompanied by large increases in hepatic cAMP and increased phosphorylation of pyruvate kinase. Metabolic effects measured after GLP administration are associated with minor, if any, increases in cAMP and effects on pyruvate kinase are variable. We hypothesize that different hepatic receptors with differing modes of intracellular message transduction are involved in glucagon and GLP actions while targetting identical metabolic routes. Responses of different species of fish cover a wide spectrum, and variation of response with the circannual cycle of experimental animals makes comparisons of results, even within one species, difficult. PMID- 24221784 TI - The relationship between T3 production and energy balance in salmonids and other teleosts. AB - Extrathyroidal T4 5'-monodeiodination, demonstrated in several teleost species, generates T3 which binds more effectively than T4 to putative nuclear receptors and is probably the active thyroid hormone. T4 to T3 conversion is sensitive to the physiological state and provides a pivotal regulatory link between the environment and thyroid hormone action. T3 generation is enhanced in anabolic states (positive energy balance or conditions favoring somatic growth; food intake or treatment with androgens or growth hormone) and is suppressed in catabolic states (negative energy balance or conditions not favoring somatic growth; starvation, stress, or high estradiol levels associated with vitellogenesis). In fish, as in mammals, thyroidal status may be finely tuned to energy balance and through T3 production regulate energy-demanding processes, which in fish include somatic growth, development and early gonadal maturation. PMID- 24221785 TI - Enhanced survival in striped bass fingerlings after maternal triiodothyronine treatment. AB - Elevation of the triiodothyronine (T3) content of striped bass (Morone saxatilis) eggs by maternal T3 injection confirms the uptake of T3 by oocytes. The resulting offspring were influenced favorably by the T3, as seen in quantitative indices of development. As reported previously, larvae from T3-supplemented eggs raised under laboratory conditions exhibited increased body area, length, dry weight, and rates of swimbladder inflation and survival, compared to controls. Also, the T3 content of unfertilized oocytes correlated positively and highly significantly with survival to two weeks of age within individual cohorts (Brownet al., 1988). In the present study, the survival of experimental and control striped bass was monitored through the fingerling stage, under hatchery production conditions. The rate of recovery of maternally T3-treated cohorts from pond-culture was approximately fourfold that of controls. The striking effects of T3 enrichment of eggs on offspring indicate the potential contribution of maternal hormones in striped bass development, and suggest possible applications in aquaculture. PMID- 24221786 TI - Hypothalamic control of prolactin release in the rainbow trout,Salmo gairdneri: in vitro studies. AB - Hypothalamic control of prolactin (PRL) release in immature rainbow troutSalmo gairdneri was investigated using anin vitro perifusion system of the rostral pars distalis. Hypothalamic extract of trout induced a dose-dependent stimulation of PRL release. A similar effect was observed when infusing the medium from a 24h static incubation of the hypothalamus. Extracts from different control tissues (muscle, liver, gut) did not changein vitro release, thus confirming the specificity of this stimulatory effect. Hypothalamic extract from adult male rat, known to contain PRL release inhibiting factors, stimulatedin vitro PRL secretion in rainbow trout. This suggests that PRL cells are predominantly influenced by PRL releasing factors. Measurement of TRH and serotonin content in trout hypothalamus indicated consistent physiological levels of these two factors. HPLC studies of hypothalamic extract showed that immunoreactive - TRH eluted at the same place as labelled TRH standard. Moreover, pizotifen, a serotonin antagonist, partially inhibited the stimulation observed with trout hypothalamic extract. These results suggest that, in immature rainbow trout, PRL release is under stimulatory hypothalamic control and that serotonin and probably TRH play a major role in this control. PMID- 24221787 TI - Changes in plasma prolactin and growth hormone concentrations during freshwater adaptation of juvenile chum salmon (Oncorhynchus keta) reared in seawater for a prolonged period. AB - Freshwater adaptability of chum salmon was examined in juvenile fish reared in seawater for 4 months. The fish, weighing about 40g, were transferred directly to fresh water in October, when their cohorts are migrating in the North Pacific Ocean. Plasma sodium concentration decreased from 167 mM in seawater to about 130 mM during the first 24h, and increased gradually during 2-7 days after the transfer. No immunoreactive prolactin (PRL) was detected in the plasma of the seawater-adapted fish nor during the first 24h in fresh water. Significant levels of PRL were detected after 2-3 days. The maximal level (2.6 ng/ml) was observed after 5 days and became undetectable again after 7 days; no significant correlation was seen between the changes in plasma sodium and PRL levels during the transfer. Plasma growth hormone levels were relatively constant, except for a significant decrease 12h after the transfer. Although plasma thyroxine levels were highly variable during the experiment, a significant decrease and an increase were observed 12h and 5 days after the transfer, respectively. The present study indicates that juvenile chum salmon retain hyperosmoregulatory ability even after prolonged rearing in seawater. Examination of turnover rates, rather than changes in plasma levels, seems to be essential to clarify the osmoregulatory roles of the hormones. PMID- 24221788 TI - Survival of salmonids in seawater and the time-frame of growth hormone action. AB - In salmonids, growth hormone (GH) effectively promotes adaptation of freshwater (FW) fish to seawater (SW), but it has been unclear whether GH has osmoregulatory actions apart from those consequent to an increase in body size. Our objectives were first, to examine the minimum time and dose required for GH to enhance SW adaptation; and second, to optimize the conditions for the acute GH response in developing a convenient GH bioassay based on its plasma ion lowering effect. Trout showed markedly improved SW survival when transferred from fresh water 6, 24, or 48h after a single chum salmon GH injection (0.25 MUg/g). Preadapting trout to 1/3 SW enhanced the plasma ion lowering effect of ovine GH (oGH) injected 48h before transfer of the fish to 80% SW. Endogenous plasma GH levels were elevated in control trout switched from low salinities to 80% SW but were depressed in oGH-injected fish after transfer. Under optimal test conditions (1/3 SW preadaptation, 48h pre-transfer injection, and 100% SW final challenge), the reduction in plasma Na(+), Ca(++), and Mg(++) levels of oGH-injected fish was dose-dependent. The oGH doses giving minimum and maximum responses were 50 and 200 ng/g, respectively. In short, GH exerts acute osmoregulatory actions that promote SW adaptation in the absence of changes in body size. Compared with growth GH bioassays, the osmoregulatory assay is superior in economy of time, animal costs, and hormone quantity required and potentially in specificity. PMID- 24221789 TI - Signals controlling renin release in aglomerular toadfish. AB - The toadfish,Opsanus tau, lacks renal glomeruli and macula densa, but has high renal renin activity and abundant granulated cells in renal arteries and arterioles. Reduction of blood pressure (BP) or blood volume by hemorrhage or vasodilatory drugs causes renin release, indicating that an intrarenal or extrarenal pressure- or volume-sensitive mechanism exists for controlling renin release in the toadfish. Thus, we examined whether 1) beta-adrenergic receptor mediated activation of renin release, and 2) calcium influx which may underlie the baroreceptor mechanism are involved in the cellular control of renin release. Acute injection of isoproterenol (1 MUg/kg, n = 6) decreased BP and increased plasma renin activity (PRA) 4-5 fold in unanesthetized toadfish. Propranolol abolished both effects, but did not decrease basal PRA levels.In vitro superfusion of renal slices with bicarbonate Ringer's solution showed a steady secretion of renin, and addition of 50 mM K(+) (K(+) methylsulfate replacing NaCl, n = 10) to the superfusate markedly suppressed renin secretion. Nifedipine (10(-5) M, n = 8) completely restored the high K(+)-induced inhibition of renin secretion from renal slices, whereas isoproterenol (10(-4) M, n = 6) neither increased basal renin secretion nor restored K(+)-induced renin suppression. These results suggest that calcium influx may mediate inhibitory messages for renin secretion, while the beta-adrenoceptor-mediated activation of granulated cells appears absent in toadfish. PMID- 24221790 TI - Control of ion transport by the sperm duct epithelium of brook trout (Salvelinus fontinalis). AB - The sperm duct epithelium of brook trout (Salvelinus fontinalis), mountedin vitro in Ussing-style epithelial chambers actively absorbs Na(+) (measured as the short circuit current, Isc) and secretes K(+) (measured using(86)Rb(+) as tracer). Dibutyryl-cyclic-adenosine monophosphate (db-cAMP) and 3-isobutyl-1 methylxanthine (IMX) produce a rapid, sustained stimulation of both ion transport processes, but the hormone connected to the response is unknown. Purified sockeye salmon CON A2 gonadotropin (GtH) produces a dose-dependent, rapid and sustained rise in Na(+) uptake and K(+) secretion. The time course, electrophysiological and transport characteristics are similar to those evoked by IMX. Carbohydrate poor (chum salmon CON A1) GtH is ineffective. Pretreatment of fish with 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P) significantly increases milt volume but is without effect on resting or stimulated (IMX + db cAMP) levels of sperm duct ion transport. This is the first indication of a direct, rapid action of GtH on ion transport by the vertebrate blood-testis barrier. The results suggest direct involvement of GtH in control of later stages of sperm maturation. PMID- 24221791 TI - Localization of calcium regulatory hormones in fish. AB - Immunocytochemical localization of hypocalcin, a hypocalcemic factor in the corpuscles of Stannius (CS), in American eels was examined at the light (ABC method) and electron microscopic (protein A-gold technique) levels with the specific antiserum raised against purified rainbow trout hypocalcin. Only type 1 cells in the CS were immunoreactive in the light microscopic immunocytochemistry. At the electron microscopic level, however, hypocalcin immunoreactivity was observed in secretory granules of both type 1 and type 2 cells. Our findings may indicate that type 1 cells are the main source of hypocalcin, but that type 2 cells also produce it, suggesting that the presence of two cell types reflects different physiological conditions of a single cell type, rather than functionally different cell types.In addition, we summarize our recent data on the localization of other calcium regulatory, or putative calcium regulatory, hormones in fish: parathyroid hormone, calcitonin and calcitonin gene-related peptide. PMID- 24221792 TI - Studies on teleost corpuscles of Stannius: Physiological and biochemical aspects of synthesis and release of hypocalcin in trout, goldfish and eel. AB - Hypercalcemia (induced by CaCl2-injection or seawater exposure of the fish) reduced the hypocalcin content of corpuscles of Stannius (CS) in trout, goldfish and eel; concomitantly the synthetic activity of CS of hypercalcemic fish, as determinedin vitro, was enhanced. The monomeric forms of prohypocalcin and of hypocalcin of trout and goldfish are 32 and 28 kDA Mr glycoprotein species respectively; those of the eel are 2 kDa bigger,viz. 34 and 30 kDa respectively. Moreover, eel CS producein vitro an enigmatic 70 kDa glycoprotein with affinity for concanavalin-A. It is concluded that plasma calcium levels control storage and synthesis rates of hypocalcin in the CS. PMID- 24221793 TI - Vitamin D3 and the renal handling of phosphate in American eels. AB - Cholecalciferol (Vitamin D3) increased plasma inorganic phosphate concentration in American eels,Anguilla rostrata, in a dose-dependent fashion. This response was more marked in phosphate loaded fish. In control as well as phosphate loaded eels the hyperphosphatemic response to D3 was associated with a sharp reduction in renal phosphate clearance relative to(14)C-polyethelene glycol (PEG) clearance. Glomerular filtration and urine flow rates were not affected by D3. As renal phosphate clearance, even in phosphate loaded eels, never significantly exceeded that of PEG, it is suggested that D3 reduced the relative clearance rate of phosphate by increasing renal phosphate reabsorption rather than by reducing the tubular secretion of phosphate. PMID- 24221794 TI - Processing and bioactivity of the corpuscles of Stannius protein of the Australian eel. AB - The primary structure of the major protein from the Corpuscles of Stannius (CS) of the Australian eel was elucidated from the cDNA sequence and was found to bear close similarity to the N-terminal amino acid sequence of the presumably homologous salmon hormone, teleocalcin (TC). The cDNA sequence predicted a preproprotein of 263 amino acids. Following removal of a 17 amino acid signal peptide, specific monobasic cleavage at an Arg-Phe bond generates the 231 amino acid mature form of the protein. The isolation and sequence determination of the prosequence confirms that the precursor contains a prosegment of 15 residues. Various fragments of the protein have been synthesized chemically and their biological activity assessed. The N-terminal 1-20 fragment of the mature protein inhibits calcium uptake in fingerling trout, the effect being similar, but not equipotent to salmon teleocalcin. Further, infusion of either the N-terminal 1-20 or the 81-94 fragment at 50 MUg/h into the renal artery of conscious sheep, caused significant decreases in systemic plasma potassium concentration and in potassium excretion. The 1-20 fragment also gave rise to a small but significant increase in sodium excretion. Infusion of TC at the same rate results in a significant decrease in plasma potassium and phosphate concentration as well as a significant decrease in potassium excretion. Bovine PTH (1-34) at 100 MUg/h causes a small decrease in plasma potassium and phosphate and an increase in plasma calcium concentration, and was the only peptide to cause a significant decrease in calcium excretion. PMID- 24221795 TI - Studies on the structure and physiology of salmon teleocalcin. AB - The structure and physiology of salmon teleocalcin, a Ca(+2) regulating hormone from the corpuscles of Stannius (CS) is reviewed. Teleocalcin is produced by the PAS+, type 1 cells in the CS. The hormone is a disulfide-linked homodimer, with a unique amino acid sequence and a carbohydrate moiety on residue 29. The teleocalcin monomer has a MW of 30 KD, whereas the pro-form of the monomer is 32 KD. The hormone is positively regulated by Ca(+2) and its function is to slow the active transport of Ca(+2) across the gill epithelium. In conjunction with prolactin, which stimulates Ca(+2) transport, teleocalcin is one of the major factors involved in Ca(+2) homeostasis in fish. PMID- 24221796 TI - Molecular cloning and expression of salmon pituitary hormones. AB - A cDNA library was prepared from chinook salmon pituitaries. Growth hormone (GH), prolactin (PRL) and the beta subunit of gonadotropin (GTH) genes were screened using synthetic oligonucleotides as probes. Full size cDNA clones coding for these polypeptide hormones were isolated and characterized. The cDNA sequences for PRL and betaGTH have been reported earlier from our laboratories. The cDNA clone for GH contains 1148 bp and codes for a preGH of 210 amino acids. The chinook salmon GH, reported in the present investigation, differs from chum salmon GH in only 1 amino acid, and from coho salmon GH in 5 amino acids. Plasmids containing modified nucleotide sequences coding for GH, PRL and betaGTH were constructed individually into an expression vector using the heat-inducible lambda pL promotor. Mature PRL, GH and unglycosylated betaGTH were expressed in the bacteria at elevated temperature. PMID- 24221797 TI - Evolutionary implications of two rainbow trout growth hormone genes. AB - The primary structures of two rainbow trout growth hormone mRNAs (GH1 and GH2) have been deduced by direct sequencing of their respective cDNA clones and portions of the mRNA. Both GH1 and GH2 mRNA contain open reading frames comprised of 630 nucleotides and encode 210 amino acid residues of which 11 are variant. The translated regions of both mRNA are flanked by a short but rather conserved 5'-end, and a relatively long but highly diverged 3'-end. The differences at translated and 3'-untranslated regions suggest that the GH1 and GH2 mRNA originate from different loci. The GH1 and GH2 mRNA are likely transcribed from two distinct loci which were duplicated during tetraploidization of salmonid genome between 50 to 100 million years ago.The GH2 gene has been isolated and sequenced from a rainbow trout genomic library. This gene spans a region of approximately 4 kilobases. The trout GH gene is comprised of 6 exons and 5 introns, in contrast to 5 exons and 4 introns in mammals. The additional intron in the trout gene interrupts the translated regions that are analogous to the last exon of the mammalian counterpart. The alleged internally repeating sequences in mammalian GH, prolactin (Pr1) and placental lactogen (PL) are not observed in the predicted polypeptide sequence of trout GH. In addition, direct repeats that flank exons I, III and V of mammalian GH, Pr1 and PL genes are absent in trout gene. These findings indicate that the rainbow trout GH gene structure does not support the current hypothesis that internally repeated regions in GH, Pr1 and PL arose from a small primordial gene. PMID- 24221798 TI - Hormonal regulation of antifreeze protein gene expression in winter flounder. AB - The essential features of experiments carried out over the past fifteen years are brought together with new data to formulate a model describing the hormonal regulation of the annual plasma antifreeze polypeptide (AFP) cycle in winter flounder (Pseudopleuronectes americanus). The precise time of onset of antifreeze synthesis in the fall appears to be regulated by photoperiod acting through the central nervous system (CNS) on the pituitary gland. During the summer, growth hormone (GH) blocks transcription of the AFP genes. With the loss of long daylengths in the fall, the CNS inhibits the release of GH allowing AFP gene transcription in the liver to proceed. In the spring GH is again released from the pituitary and AFP gene transcription is blocked. PMID- 24221799 TI - Endocrinology and fish farming: Aspects in reproduction, growth, and smoltification. PMID- 24221800 TI - Cyclostome workshop. PMID- 24221801 TI - Transgenic fish: present status and future directions. AB - Successful production of transgenic fish by gene transfer technology is a very important breakthrough in the techniques of genetic manipulation in animals. This will have an impact of an unprecedented scale in fish biology, aquaculture and mariculture. This is a summary of the workshop on the Transgenic Fish presented at this Symposium. The Workshop discussed the current knowledge, experimental difficulties and related topics of the transgenic fish. It recommended further research on better gene constructs, methods development, safety containment and the closer collaboration of researchers of different disciplines. PMID- 24221802 TI - Some perspectives on fish endocrinology. PMID- 24221804 TI - Antiplatelet therapy in prevention of cardio- and venous thromboembolic events. AB - The contribution of platelets in the pathophysiology of low-shear thrombosis specifically, in atrial fibrillation (AF) and venous thromboembolic events (VTE) remains less clear than for arterial thrombosis. AF itself appears to lead to platelet activation, offering a potential target for aspirin and other antiplatelet agents. Randomized trial results suggest a small benefit of aspirin over placebo, and of dual antiplatelet therapy (aspirin plus clopidogrel) over aspirin alone, for prevention of cardioembolic events in AF. Antiplatelet therapy thus can represent an option for patients with AF who are unsuitable for therapy with warfarin or novel oral anticoagulant agents. For VTE, the rationale for antiplatelet therapy reflects the venous response to disrupted blood flow interactions among monocytes, neutrophil extracellular traps, and platelets. Early randomized trials generally showed poorer performance of aspirin relative to heparins and danaparoid sodium in prevention of VTE. However, results from large placebo- and dalteparin-controlled randomized trials have spurred changes in the most recent practice guidelines-aspirin is now recommended after major orthopedic surgery for patients who cannot receive other antithrombotic therapies. PMID- 24221808 TI - Veterinarians and the Institute of Medicine. PMID- 24221805 TI - Comparison of cost-effectiveness of anticoagulation with dabigatran, rivaroxaban and apixaban in patients with non-valvular atrial fibrillation across countries. AB - We did a cost-utility analysis for the new oral anticoagulants (NOACs) in the German population based on the quality-adjusted life years (QALY), total costs, and incremental cost-effectiveness ratios (ICER). The aim of our investigation was to examine cost-utility for current German drug market costs and compared to other countries. Outcome data were taken from dabigatran's RE-LY, rivaroxaban's ROCKET AF, and apixaban's ARISTOTLE trials. A Markov decision model, the Monte Carlo simulation (MCS), and further sensitivity analyses were used to simulate comparisons between NOACs over a follow up period of 20 years. The main perspective used for the analyses is from a German public health care insurance perspective. The base-case analyses of a 65 years old person with a CHADS2 score >1 resulted in 7.56-7.64 QALYs gained for warfarin. NOACs added 0.04-0.19 QALYs. Total costs for warfarin ranged from 7622 to 9069 and for NOACs from 19537 to 20048. The sensitivity analysis indicated that current German market costs for the NOACs exceed a willingness-to-pay threshold of (hypothetical) 50000/QALY in all treatment regimen. The MCS showed willingness-to-pay thresholds from 60500/QALY for apixaban to 278000/QALY for dabigatran 110 mg bid, with values for dabigatran 150 mg bid and rivaroxaban in between. In conclusion, from a German public health care insurance perspective current market costs are high in relation to the quality of life gained. These results from clinical studies (efficacy) remain to be confirmed under real life conditions (effectiveness). PMID- 24221812 TI - Middle East respiratory syndrome (MERS) coronavirus: a new challenge for veterinarians? PMID- 24221813 TI - Pneumoperitoneum in a patient with Larsen syndrome. PMID- 24221814 TI - Green, scalable, binderless fabrication of a single-walled carbon nanotube nonwoven fabric based on an ancient Japanese paper process. AB - We propose a fabrication method for carbon nanotube (CNT) nonwoven fabrics based on an ancient Japanese papermaking process where paper is made from natural plant fibers. In our method, CNT nonwoven fabrics are made by a scalable process of filtering binder-free, aqueous suspensions of CNTs. The aqueous suspension of these entangled single-walled carbon nanotube (SWNT) aggregates enabled smooth filtration through a cellulose filter with large pores (8 MUm). The "wet SWNT cakes," which were composed solely of SWNT and water and obtained after filtration, were press-dried to fabricate an SWNT nonwoven fabric. This environmentally friendly process employs water and the raw CNT material alone. Moreover, the scalability of this process was demonstrated by manufacturing a large area (A3, 30 * 42 cm; thickness: 40-150 MUm), self-supporting SWNT nonwoven fabric with a density of 0.4 g/cm(3), a basis weight of 0.2 g/m(2) , a porosity of 63%, and a specific surface area of 740 m(2)/g. This SWNT nonwoven fabric is anticipated to find application as functional particle-supported sheets, electrode materials, and filters. PMID- 24221815 TI - Exceptionally large solitary fibrous tumor arising from the cheek: an immunohistochemical and ultrastructural study with a review of the literature. AB - Solitary fibrous tumor (SFT) is a rare mass-forming soft tissue tumor that occurs most commonly in the pleura, but has been described in various extrathoracic sites. Extrapleural manifestation of SFT, particularly in the head and neck region, is rare. The most common extrapleural site is the oral cavity; these tumors have also been described in the orbit, nasopharynx, paranasal sinuses, salivary glands, and larynx. We report an extremely rare case of a SFT in the subcutaneous region of the cheek. This tumor in the left cheek was a large firm mass, approximately 8.5 cm * 6 cm in size and was successfully treated by surgical resection. Immunohistochemistry revealed reactivity for vimentin, CD34, and bcl-2, but no staining for cytokeratin, epithelial membrane antigen, S-100, desmin, caldesmon, actin, alpha-smooth muscle actin, CD117, and CD99. Immunohistochemical study is the key to establish a definitive diagnosis of SFT, and ultrastructural study is also useful for making an accurate diagnosis. The patient recovered uneventfully without evidence of tumor recurrence 2 years after surgery. PMID- 24221816 TI - Being a girl in a boys' world: investigating the experiences of girls with autism spectrum disorders during adolescence. AB - This study investigates the experiences of adolescent girls with autism spectrum disorders (ASD) during adolescence. Semi-structured interviews were conducted with three mother-daughter dyads and two additional mothers. A range of issues were highlighted covering physical, emotional, social and sexual domains. Some of these issues were similar to those experienced by boys with ASD during adolescence, such as negative implications of late diagnosis, challenges of transitioning to and coping with high school, 'hands-on' role of parents into adolescence, difficulties adjusting to the increased demands of adolescent hygiene routines, and the importance of learning personal boundaries in interactions with others. Other issues discussed were of particular relevance to adolescent girls with ASD, such as difficulties socialising with neurotypically developing girls, sex-specific puberty issues, and sexual vulnerabilities. This study highlights an important research area and is a preliminary step towards understanding the experiences of adolescent girls with ASD and their families. PMID- 24221818 TI - Evaluation of surface colonization kinetics in continuous culture. AB - Two equations, describing surface colonization, were evaluated and compared using suspended glass slides in a continuous culture ofPseudomonas aeruginosa. These equations were used to determine surface growth rates from the number and distribution of cells present on the surface after incubation. One of these was the colonization equation which accounts for simultaneous attachment and growth of bacteria on surfaces:[Formula: see text] where N=number of cells on surface (cells field(-1)); A=attachment rate (cells field(-1)h(-1));MU=specific growth rate (h(-1)); t=incubation period (h). The other was the surface growth rate equation which assumes that the number of colonies of a given size (Ci) will reach a constant value (Cmax) which is equal to A divided byMU:[Formula: see text] Both equations gave similar results and the time required to approximate Cmax may not be as long as was previously thought. In all cases both A andMU continuously decreased throughout the incubation period. These decreases may be due to various effects of microbial accumulation on the surface. Both equations accurately determined surface growth rates despite highly variable attachment rates. Growth rates were similar for both the liquid phase of the culture and the solid-liquid interface (0.4 h(-1)). Use of the surface growth rate equation is favored over the use of the colonization equation since the former does not require a computer to solve forMU and the counting procedure is simplified. PMID- 24221817 TI - Lower electrodermal activity to acute stress in caregivers of people with autism spectrum disorder: an adaptive habituation to stress. AB - Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between parents of people with (n = 30) and without (n = 34) ASD (caregivers and non-caregivers, respectively). Caregivers showed lower EDA in response to acute stress than non-caregivers. They also presented higher trait anxiety, anger, depression, and somatic symptoms than non-caregivers. Higher EDA was related to a worse mood and more severe somatic symptoms only in caregivers. These results could reflect an adaptive habituation to stress and establish that high EDA in response to acute stress depends on caregivers' health. PMID- 24221819 TI - Surface attachment of a sediment isolate ofEnterobacter cloacae. AB - Enterobacter cloacae was recovered from surface sediments of a flood control channel in an area where freshwater runoff mixed with coastal seawater. Cells of this bacterium elaborated an extensive capsule when cultured under laboratory conditions designed to promote extracellular polysaccharide production. Colonization of glass surfaces by cells was similar under aerobic and anaerobic conditions. Temperature exerted little effect on maximum adherent cell density in the range of 15-25 degrees C. The availability of organic nutrients also had little influence on the tendency of cells to adhere to surfaces. Maximum adherent cell densities decreased (76%) as salinity increased from 0 to 120/00 The results suggest that cells ofE. cloacae are suitably adapted to maintain a sessile existence in brackish water sediments of temperate coastal areas. PMID- 24221820 TI - Bacterial activity at the air/water interface. AB - By using substrate molecules of varying degrees of surface activity, we were able to measure some features of bacterial activity in the surface microlayers (SM) and in the subsurface (bulk) water. The fraction of active cells was determined by a combined microautoradiography-epifluorescence (ME) method. Measurements were made of(14)CO2 evolution to determine the rate of respiration. Results from in situ measurements showed no significant difference between fraction of active cells in the SM and in the bulk. This may be due to an exchange of bacteria between SM and bulk. This exchange was assessed by spreading a film of(3)H palmitic acid on the surface and, after incubation, measuring the amount of labeled cells at the surface and in the bulk. Test bacteria showing a high accumulation at the surface also showed a low exchange between the 2 strata. When low concentrations of added(14)C-protein were used, the respiration measurements showed a lower value for bulk than for interface localized protein. At higher concentrations, the evolved(14)CO2 was the same whether the protein was mixed in the bulk or spread at the surface. When 2.4-12 ng.cm(-2) of(14)C-palmitic acid was spread on the surface, there was a linear relation between turnover time and amount of added substrate. At higher substrate concentrations there was a deviation from the straight line. Results are discussed in terms of the unique habitat found at an interface. PMID- 24221821 TI - Effects of freeze-thaw stress on bacterial populations in soil microcosms. AB - To test the effect of freezing on soil biota, isolated from the shortgrass prairie of northeastern Colorado, a series of experiments were performed using gnotobiotic soil microcosms.Pseudomonas paucimobilis was used to examine the effects of freezing on bacteria of different growth stages. Secondly, the effect of multiple freeze-thaw cycles was tested on an assemblage of bacterial species. Lastly, the effect of freezing on predator-prey interactions was studied usingP. paucimobilis and an amoebal predator,Acanthamoeba polyphaga. A temperature of -9 degrees C was not detrimental toP. paucimobilis at any growth stage. A single severe freeze-thaw cycle (-27 degrees C to 23 degrees C) resulted in 40-60% mortality ofP. paucimobilis and the mixed bacteria, although additional freezing events did not reduce the populations further. Multiple freeze-thaw cycles (-9 degrees C to 23 degrees C) gave 40-60% mortality ofP. paucimobilis and the mixed bacteria. Predator-prey population cycles were possibly desynchronized by freeze thaw events. PMID- 24221822 TI - Competition for L-lactate betweenDesulfovibrio, Veillonella, andAcetobacterium species isolated from anaerobic intertidal sediments. AB - Almost equal numbers ofDesulfovibrio, Veillonella, andAcetobacterium species were found in agar shake dilutions of anaerobic intertidal brackish sediments applying L-lactate as the only energy source and sulfate as electron acceptor. Pure cultures of these bacteria were studied in more detail in batch cultures as well as in L-lactate-limited chemostats. The maximal specific growth rates on L lactate were determined in washout experiments and amounted to 0.16, 0.30, and 0.06 h(-1) forDesulfovibrio baculatus H.L21,Veillonella alcalescens NS.L49, andAcetobacterium NS.L40, respectively. Competition for L-lactate was studied in energy-limited chemostats at a dilution rate of 0.02 h(-1).D. baculatus H.L21 turned out to be the best competitor at low L-lactate concentrations provided that sufficient sulfate and iron were present.V. alcalescens NS.L49 was favored by the absence of sulfate and iron. Coexistence ofD. baculatus H.L21 andV. alcalescens NS.L49 was observed in a L-lactate-limited chemostat with additional sulfate and citrate. Syntrophic growth ofV. alcalescens NS.L49 andAcetobacterium NS.L40 occurred in a L-lactate-limited chemostat in the absence of sulfate. No coexistence betweenD. baculatus H.L21 andAcetobacterium NS.L40 was observed in a L-lactate-limited chemostat without sulfate. Addition of calcium-saturated illite to an energy-limited mixed culture ofV. alcalescens NS.L49 andAcetobacterium NS.L40 induced iron limitation and subsequent washout of theAcetobacterium species. Finally, the ecological niches of the 3 species in relation to the consumption of lactate were discussed. PMID- 24221823 TI - Microbial decomposition of leaf material at 0 degrees C. AB - The microbial decomposition of leaves (both fresh and autumnshed) at 0 degrees C using stream sediment-water was investigated. The maximum rates of loss of leaf carbohydrate and protein at 0 degrees C were considerable, being about 40% of those at 20 degrees C. These rates were only slightly affected by the type of leaf material present being 1.3-fold higher with fresh leaves as compared with autumn-shed leaves. In addition, an epifluorescence microscopic counting technique was developed and utilized to enumerate the microbial populations colonizing the decomposing leaves. The average microbial densities on fresh and autumn-shed leaves after 35 days of incubation were 1.3 * 10(6) and 9.0 * 10(5) microorganisms cm(-2) at 0 degrees C as compared with 5.5 * 10(6) and 3.3 * 10(6) microorganisms cm(-2) at 20 degrees C, respectively. Antibacterial and antifungal antibiotics were used to estimate the comparative involvement of sediment bacteria and fungi in leaf degradation. PMID- 24221824 TI - Effects of mineral nutrients, sludge application rate, and application frequency on biodegradation of two oily sludges. AB - A continuous flow soil respirometer was used to evaluate the effect of nutrient addition, application rate, and application frequency on biodegradation of 2 complex oily sludges in soil. The most rapid biodegradation of the refinery sludge occurred when nitrogen was added to reduce the carbon to nitrogen (C?N) ratio to 9?1. The petrochemical sludge was degraded most rapidly when nitrogen, phosphorus, and potassium were added at a rate of 124?1, C?NPK; CO2evolution from both wastes increased with increasing application rates, but the fraction of applied sludge which degraded decreased with increasing application rates. Small frequent applications resulted in a slight increase in respiration rate per unit applied over a single equivalent application, indicating that repeated applications of smaller amounts of sludge result in a more rapid rate of decomposition. The population of total soil bacteria was greatest when 1% of either sludge was added to the soil, whereas 5 and 10% sludge additions resulted in slightly lower microbial populations. PMID- 24221825 TI - Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6 J mice. AB - RATIONALE: Although non-medical use of oxycodone continues to be a growing problem in the United States, there are no animal studies examining the effects of long-term oxycodone self-administration (SA). OBJECTIVES: The current study was designed to examine chronic oxycodone SA by mice (14 days), in novel extended (4 h) SA sessions and its effect on selective striatal neurotransmitter receptor mRNA expression. METHODS: Adult male C57/BL6J mice were either allowed to self administer oxycodone (0.25 mg/kg/infusion, FR1) or served as yoked-saline controls in an extended access paradigm. Mice self-administered oxycodone for 4 h/day for 14 consecutive days. Comparison groups with 14-days exposure to 1-h SA sessions were also studied. Within 1 h of the last extended SA session, mice were sacrificed, dorsal striatum was isolated and selective neurotransmitter receptor mRNA levels were examined. RESULTS: The oxycodone groups poked the active hole significantly more times than the yoked controls. The number of nose pokes at the active hole rose over the 14 days in the oxycodone group with extended access. The expression of 13 neurotransmitter receptor mRNAs was significantly altered in the dorsal striatum, including the gamma-aminobutyric acid (GABA) A receptor beta 2 subunit (Gabrb2) showing experiment-wise significant decrease, as a result of extended oxycodone SA. CONCLUSION: C57BL/6 J mice escalated the amount of oxycodone self-administered across 14 consecutive daily extended sessions, but not 1-h sessions. Decreases in Gabrb2 mRNA levels may underlie escalation of oxycodone intake in the extended access SA sessions. PMID- 24221826 TI - Dopamine D1 and MU-opioid receptor antagonism blocks anticipatory 50 kHz ultrasonic vocalizations induced by palatable food cues in Wistar rats. AB - RATIONALE: Fifty kilohertz ultrasonic vocalizations (USVs) have been sometimes shown to reflect positive affective-like states in rats. Rewarding events, such as access to palatable food or drugs of abuse, increase the number of anticipatory 50-kHz USVs. However, little is known about the predictability of USVs, subtypes of USVs involved, and underlying neurobiological mechanisms. OBJECTIVES: We examined whether cue-induced anticipatory 50-kHz USVs predict palatable food intake and tested the effects of dopamine D1 and MU-opioid receptor antagonism on anticipatory USVs. MATERIALS: Food-restricted rats received repeated sessions of a 2-min cue light immediately followed by a 5-min access to palatable food. Ultrasonic vocalizations were recorded during cue presentation. After 24 pairing sessions, the rats were pretreated with the D1 receptor antagonist SCH 23390 (5, 10, and 20 MUg/kg) and MU-opioid receptor antagonist naltrexone (0.03, 0.06, 0.13, 0.25, 0.5, and 1 mg/kg) in a Latin square design, and USVs were recorded during cue presentation. RESULTS: Rats emitted 50-kHz USVs during cue presentation, and the number of USVs increased across sessions with robust and stable interindividual differences. Escalation in USVs was subtype-dependent, with nontrill calls significantly increasing over time. Palatable food intake was positively correlated with anticipatory 50-kHz USVs. Moreover, anticipatory USVs were dose-dependently prevented by antagonism of D1 and MU-opioid receptors. CONCLUSIONS: These findings demonstrate that anticipatory 50-kHz USVs represent a stable phenotype of increased motivation for food, and dopamine and opioid systems appear to mediate anticipatory 50-kHz USVs. PMID- 24221827 TI - Antidepressants share the ability to increase catecholamine output in the bed nucleus of stria terminalis: a possible role in antidepressant therapy? AB - RATIONALE: Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria teminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. OBJECTIVES: The aim of this study, carried out by means of in vivo microdialysis, was to ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST. RESULTS: We observed that all the antidepressants tested (5-20 mg/kg i.p.) increased the output of catecholamines, dose dependently. In particular, the maximum increases (as a percent of basal) for norepinephrine and dopamine respectively, were as follows: desipramine, 239 and 137; reboxetine, 185 and 128; imipramine, 512 and 359; citalopram, 95 and 122; fluoxetine, 122 and 68; bupropion, 255 and 164. CONCLUSIONS: These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders. PMID- 24221828 TI - Social play behavior, ultrasonic vocalizations and their modulation by morphine and amphetamine in Wistar and Sprague-Dawley rats. AB - RATIONALE: Social play behavior is the most characteristic social behavior in young mammals. It is highly rewarding and crucial for proper neurobehavioral development. Despite the importance of genetic factors in normal and pathological social behaviors, little information is available about strain influences on social play. OBJECTIVE AND METHODS: The aim of this study was to investigate differences in social play behavior, 50-kHz ultrasonic vocalizations (USVs) and their modulation by acute morphine and amphetamine administration in two rat strains widely used in behavioral pharmacology studies, i.e., Wistar and Sprague Dawley rats. RESULTS: Sprague-Dawley rats showed higher levels of social play than Wistar rats. In both strains, no correlation was found between the performance of social behaviors and the emission of 50-kHz USVs. In Wistar and Sprague-Dawley rats, morphine increased and amphetamine decreased social play. The effects of morphine, however, were more pronounced in Wistar than Sprague Dawley animals. In both strains, morphine did not affect USV emission, while amphetamine increased it during cage exploration. In Sprague-Dawley rats only, amphetamine decreased USVs during social interaction. CONCLUSIONS: Wistar and Sprague-Dawley rats differ in their absolute levels of social play behavior and 50-kHz USVs, and quantitative differences exist in their response to pharmacological manipulations of social play. The emission of 50-kHz USVs and the behavioral parameters thought to reflect rewarding social interactions in adolescent rats are dissociable. PMID- 24221829 TI - High prevalence of hypertension among collegiate football athletes. AB - BACKGROUND: The prevalence of hypertension among collegiate football athletes is not well described. METHODS AND RESULTS: A retrospective cohort of all male athletes who participated in varsity athletics at a National Collegiate Athletic Association Division I university between 1999 and 2012 was examined through chart review. Mandatory annual preparticipation physical examinations included blood pressure, body mass index, medication use, and supplement use. Prevalence of hypertension was compared between football and nonfootball athletes. A mixed effects linear regression model examined change in blood pressure over time. Six hundred thirty-six collegiate athletes, including 323 football players, were identified. In the initial year of athletic participation, 19.2% of football athletes had hypertension and 61.9% had prehypertension. The prevalence of hypertension was higher among football athletes than in nonfootball athletes in their initial (19.2% versus 7.0%; P<0.001) and final (19.2% versus 10.2%; P=0.001) years of athletic participation. In adjusted analyses, the odds of hypertension were higher among football athletes in the initial year (adjusted odds ratio, 2.28; 95% confidence interval, 1.21-4.30) but not in the final year (adjusted odds ratio, 1.25; 95% confidence interval, 0.69-2.28). Over the course of their collegiate career, football athletes had an annual decrease in systolic blood pressure (-0.82 mm Hg; P=0.002), whereas nonfootball athletes did not (0.18 mm Hg; P=0.58). CONCLUSIONS: Hypertension and prehypertension were common among collegiate football athletes, and football athletes were more likely to have hypertension compared with male nonfootball athletes. This presents a potential cardiovascular risk in a young population of athletes. Strategies for increasing awareness, prevention, and treatment are needed. PMID- 24221830 TI - Influence of cardiac surgeon report cards on patient referral by cardiologists in New York state after 20 years of public reporting. AB - BACKGROUND: Report cards of risk-adjusted mortality rates of individual cardiac surgeons have been publicly available in New York State since 1991. A survey of New York cardiologists in 1996 found that these report cards had little effect on their referral recommendations to cardiac surgeons. It is unknown whether the influence of report cards on referral behavior has changed over time. METHODS AND RESULTS: We surveyed cardiologists in New York State in 2011 to determine their awareness of cardiac surgeon report cards, their use of the report card in formulating judgments about the quality of cardiac surgeons and selecting cardiac surgeons for referral of patients, and discussion of the report with patients in need of cardiac surgery. The relation between demographic (age, sex) and professional (teaching, board certification, faculty appointment, general cardiology practice, and hospital employee) characteristics and the influence of report cards on referral decisions was assessed using chi(2) for categorical variables and t test for continuous variables. Multivariable logistic regression models were created to determine the independent association of any variable with P<0.1 on univariate analysis. Almost all (94%) cardiologists were aware of report cards of cardiac surgeons. The influence of the report cards on cardiologists' referral decisions was limited, with 25% of cardiologists reporting a moderate or substantial influence on referral decisions. The report card was not discussed with any patients by 71% of cardiologists. The mean age of cardiologists reporting moderate or substantial influence of report cards was 58 years compared with 54 years for those who reported no/little influence (P=0.012). Fewer cardiologists who reported moderate or substantial influence were board certified (91% versus 99%; P=0.003). On multivariate analysis, general cardiology practice and employment by a hospital were independently associated with greater report card influence (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P=0.13). CONCLUSIONS: After 20 years of public reporting and almost universal awareness of cardiac surgeon report cards, in 2011, cardiologists in New York State made little use of this information and rarely discussed it with patients at the time of referral for cardiac surgery. PMID- 24221831 TI - Association between a hospital's quality performance for in-hospital cardiac arrest and common medical conditions. AB - BACKGROUND: Public reporting on hospital quality has been widely adopted for common medical conditions. Adding a measure of inpatient survival after cardiac arrest is being considered. It is unknown whether this measure would be redundant, given evidence that hospital organization and culture can have hospital-wide effects on quality. Therefore, we sought to evaluate the correlation between inpatient survival after cardiac arrest and 30-day risk standardized mortality rates for common medical conditions. METHODS AND RESULTS: Using data between 2007 and 2010 from a national in-hospital cardiac arrest registry, we calculated risk-standardized in-hospital survival rates for cardiac arrest at each hospital. We obtained risk-standardized 30-day mortality rates for acute myocardial infarction, heart failure, and pneumonia from Hospital Compare for the same period. The relationship between a hospital's performance on cardiac arrest and these other medical conditions was assessed using weighted Pearson correlation coefficients. Among 26 270 patients with in-hospital cardiac arrest at 130 hospitals, survival rates varied across hospitals, with a median risk standardized hospital survival rate of 22.1% and an interquartile range of 19.7% to 24.2%. There were no significant correlations between a hospital's outcomes for its cardiac arrest patients and its patients admitted for acute myocardial infarction (correlation, -0.12; P=0.16), heart failure (correlation, -0.05; P=0.57), or pneumonia (correlation, -0.15; P=0.10). CONCLUSIONS: Hospitals that performed better on publicly reported outcomes for 3 common medical conditions did not necessarily have better cardiac arrest survival rates. Public reporting on cardiac arrest outcomes could provide new information about hospital quality. PMID- 24221833 TI - Most important outcomes research papers on body weight, obesity and cardiovascular outcomes. PMID- 24221832 TI - Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation. AB - BACKGROUND: New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective. METHODS AND RESULTS: A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost effectiveness threshold of $100 000 per quality-adjusted life year. CONCLUSIONS: While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money. PMID- 24221834 TI - Differences in the profile, treatment, and prognosis of patients with cardiogenic shock by myocardial infarction classification: A report from NCDR. AB - BACKGROUND: Cardiogenic shock is a deadly complication of an acute myocardial infarction (MI). We sought to characterize differences in patient features, treatments, and outcomes of cardiogenic shock by MI classification: ST-segment elevation MI (STEMI) versus non-ST-segment elevation MI (NSTEMI). METHODS AND RESULTS: We compared differences in care by the shock status of 235 541 patients with STEMI and NSTEMI treated at 392 US hospitals from 2007 to 2011. Cardiogenic shock occurred in 12.2% of patients with STEMI versus 4.3% of patients with NSTEMI. Compared with STEMI shock, NSTEMI shock was more likely in patients who were older and predominantly women; had diabetes mellitus, hypertension, previous heart failure, MI, or peripheral arterial disease; and who received coronary artery bypass grafting (11.6% versus 21.2%; P<0.0001) but less likely to have received percutaneous coronary intervention (84.2% versus 35.3%; P<0.0001). Compared with patients with STEMI presenting with shock at admission, patients with NSTEMI presenting with shock had longer delays to percutaneous coronary intervention (1.2 versus 3.2 hours) and coronary artery bypass grafting (7.9 versus 55.9 hours). Cardiogenic shock in patients with STEMI was associated with a lower mortality risk (33.1% shock versus 2.0% no shock; adjusted odds ratio, 14.1; 95% confidence interval, 13.0-15.4; interaction P value <0.0001) compared with patients with NSTEMI (40.8% shock versus 2.3% no shock, odds ratio, 19.0; 95% confidence interval, 17.1-21.2). CONCLUSIONS: Cardiogenic shock is associated with high mortality in patients with STEMI and NSTEMI. However, urgent revascularization is more commonly pursued in patients with STEMI presenting with shock than in patients with NSTEMI. More research is needed to improve the outcomes for patients with MI presenting with shock, particularly those presenting with NSTEMI. PMID- 24221835 TI - Psychological distress and medication adherence: creating order out of chaos? PMID- 24221837 TI - Influence of cardiac surgeon report cards on patient referral by cardiologists in New York state after 20 years of public reporting. PMID- 24221838 TI - The China Patient-Centered Evaluative Assessment of Cardiac Events (China PEACE) retrospective study of acute myocardial infarction: study design. AB - BACKGROUND: Cardiovascular diseases are rising as a cause of death and disability in China. To improve outcomes for patients with these conditions, the Chinese government, academic researchers, clinicians, and >200 hospitals have created China Patient-Centered Evaluative Assessment of Cardiac Events (China PEACE), a national network for research and performance improvement. The first study from China PEACE, the Retrospective Study of Acute Myocardial Infarction (China PEACE Retrospective AMI Study), is designed to promote improvements in acute myocardial infarction (AMI) quality of care by generating knowledge about the characteristics, treatments, and outcomes of patients hospitalized with AMI across a representative sample of Chinese hospitals during the past decade. METHODS AND RESULTS: The China PEACE-Retrospective AMI Study will examine >18 000 patient records from 162 hospitals identified using a 2-stage cluster sampling design within economic-geographic regions. Records were chosen from 2001, 2006, and 2011 to identify temporal trends. Data quality will be monitored by a central coordinating center and will, in particular, address case ascertainment, data abstraction, and data management. Analyses will examine patient characteristics, diagnostic testing patterns, in-hospital treatments, in-hospital outcomes, and variation in results by time and site of care. In addition to publications, data will be shared with participating hospitals and the Chinese government to develop strategies to promote quality improvement. CONCLUSIONS: The China PEACE Retrospective AMI Study is the first to leverage the China PEACE platform to better understand AMI across representative sites of care and during the past decade in China. The China PEACE collaboration among government, academicians, clinicians, and hospitals is poised to translate research about trends and patterns of AMI practices and outcomes into improved care for patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624883. PMID- 24221839 TI - Association between perceived life chaos and medication adherence in a postmyocardial infarction population. AB - BACKGROUND: The benefits of medication adherence to control cardiovascular disease (CVD) are well defined, yet multiple studies have identified poor adherence. The influence of life chaos on medication adherence is unknown. Because this is a novel application of an instrument, our preliminary objective was to understand patient factors associated with chaos. The main objective was to evaluate the extent to which an instrument designed to measure life chaos is associated with CVD-medication nonadherence. METHODS AND RESULTS: Using baseline data from an ongoing randomized trial to improve postmyocardial infarction (MI) management, multivariable logistic regression identified the association between life chaos and CVD-medication nonadherence. Patients had hypertension and a myocardial infarction in the past 3 years (n=406). Nearly 43% reported CVD medication nonadherence in the past month. In simple linear regression, the following were associated with higher life chaos: medication nonadherence (beta=1.86; 95% confidence interval [CI], 0.96-2.76), female sex (beta=1.22; 95% CI [0.22-2.24]), minority race (beta=1.72; 95% CI [0.78-2.66]), having less than high school education (beta=2.05; 95% CI [0.71-3.39]), low health literacy (beta=2.06; 95% CI [0.86-3.26]), and inadequate financial status (beta=1.93; 95% CI [0.87-3.00]). Being married (beta=-2.09, 95% CI [-3.03 to -1.15]) was associated with lower life chaos. As chaos quartile increased, patients exhibited more nonadherence. In logistic regression, adjusting for sex, race, marital status, employment, education, health literacy, and financial status, a 1-unit life chaos increase was associated with a 7% increase (odds ratio, 1.07; 95% CI [1.02-1.12]) in odds of reporting medication nonadherence. CONCLUSIONS: Our results suggest that life chaos may be an important determinant of medication adherence. Life chaos screenings could identify those at risk for nonadherence. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT000901277. PMID- 24221840 TI - Check it, change it: a community-based intervention to improve blood pressure control. AB - BACKGROUND: Despite the widespread availability of effective and affordable therapies, hypertension remains this country's most significant modifiable cardiovascular risk factor. Approximately 30% to 50% of individuals with hypertension currently fail to reach guideline-recommended target blood pressure (BP) goals. Although multiple interventions have been proposed to affect better hypertension control, the integration of multiple elements in a community-based program has not been evaluated to date. METHODS AND RESULTS: We created a broadly inclusive community-based initiative to control hypertension called Check It, Change It: The Durham Blood Pressure Challenge (CICI). We enrolled ~2000 participants with hypertension in 8 ambulatory clinics across Durham County, NC. The CICI program engaged individuals by providing them with tools for self monitoring and tied this information to their caregivers via a web-based portal (the American Heart Association's Heart360, a remote BP monitoring system). Additionally, the CICI facilitated clinical intervention of high-risk individuals using physician assistants and community health coaches. The primary outcome will be a change in BP during the 6 months postenrollment in the program, which will be compared with concurrent and historical control populations of nonparticipants. CONCLUSIONS: We think that this integrated and tiered approach will lead to improved BP control within 6 months. If successful, the CICI program has the potential to enhance community-level BP control. PMID- 24221841 TI - The YOU CALL-WE CALL randomized clinical trial: Impact of a multimodal support intervention after a mild stroke. AB - BACKGROUND: Comparison of a multimodal intervention WE CALL (study initiated phone support/information provision) versus a passive intervention YOU CALL (participant can contact a resource person) in individuals with first mild stroke. METHODS AND RESULTS: This study is a single-blinded randomized clinical trial. Primary outcome includes unplanned use of health services (participant diaries) for adverse events and quality of life (Euroquol-5D, Quality of Life Index). Secondary outcomes include planned use of health services (diaries), mood (Beck Depression Inventory II), and participation (Assessment of Life Habits [LIFE-H]). Blind assessments were done at baseline, 6, and 12 months. A mixed model approach for statistical analysis on an intention-to-treat basis was used where the group factor was intervention type and occasion factor time, with a significance level of 0.01. We enrolled 186 patients (WE=92; YOU=94) with a mean age of 62.5 +/- 12.5 years, and 42.5% were women. No significant differences were seen between groups at 6 months for any outcomes with both groups improving from baseline on all measures (effect sizes ranged from 0.25 to 0.7). The only significant change for both groups from 6 months to 1 year (n=139) was in the social domains of the LIFE-H (increment in score, 0.4/9 +/- 1.3 [95% confidence interval, 0.1-0.7]; effect size, 0.3). Qualitatively, the WE CALL intervention was perceived as reassuring, increased insight, and problem solving while decreasing anxiety. Only 6 of 94 (6.4%) YOU CALL participants availed themselves of the intervention. CONCLUSIONS: Although the 2 groups improved equally over time, WE CALL intervention was perceived as helpful, whereas YOU CALL intervention was not used. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN95662526. PMID- 24221843 TI - Outsourcing and contract services. PMID- 24221842 TI - FRET-based calcium imaging: a tool for high-throughput/content phenotypic drug screening in Alzheimer disease. AB - Perturbed intracellular store calcium homeostasis is suggested to play a major role in the pathophysiology of Alzheimer disease (AD). A number of mechanisms have been suggested to underlie the impairment of endoplasmic reticulum calcium homeostasis associated with familial AD-linked presenilin 1 mutations (FAD-PS1). Without aiming at specifically targeting any of those pathophysiological mechanisms in particular, we rather performed a high-throughput phenotypic screen to identify compounds that can reverse the exaggerated agonist-evoked endoplasmic reticulum calcium release phenotype in HEK293 cells expressing FAD-PS1. For that purpose, we developed a fully automated high-throughput calcium imaging assay using a fluorescence resonance energy transfer-based calcium indicator at single cell resolution. This novel robust assay offers a number of advantages compared with the conventional calcium measurement screening technologies. The assay was employed in a large-scale screen with a library of diverse compounds comprising 20,000 low-molecular-weight molecules, which resulted in the identification of 52 primary hits and 4 lead structures. In a secondary assay, several hits were found to alter the amyloid beta (Abeta) production. In view of the recent failure of AD drug candidates identified by target-based approaches, such a phenotypic drug discovery paradigm may present an attractive alternative for the identification of novel AD therapeutics. PMID- 24221845 TI - Application of gas-permeable bags for in vitro cold storage of strawberry germplasm. AB - This study reports the first use of gaspermeable, heat-sealable polyethylene bags for cold storage of plant tissue cultures. The bags were used to develop a new cold storage system for the in vitro strawberry collection at the National Clonal Germplasm Repository (NCGR), Corvallis. In vitro Fragaria plantlets of 96 different accessions (species and cultivars) were transferred to bags with basal medium without growth regulators, heat-sealed, grown for one week at 25 degrees C, cold hardened for one week, and then stored in the dark at 4 degrees C. These in vitro cultures were successfully stored for up to 24 months in polyethylene bags. Evaluations at three month intervals provided information on the condition of the diverse collection. Over 75% of the accessions originally stored remained in storage for 15 months and 47% remained for over 18 months. None of the 96 accessions studied was lost due to contamination or decline in vigor. Over 300 Fragaria accessions are currently stored using this system. PMID- 24221846 TI - Volatiles identified from five stages of embryo development separated from a heterogeneous suspension culture of Daucus carota. AB - Five stages of embryo development were fractionated from a mature culture of Daucus carota (Gelbe Rheinsche), using a series of metal sieves. The composition of the population of embryos in each fraction was determined quantitatively from microscopic investigations. Volatiles from samples of tissue from six stages of development were trapped on activated charcoal cartridges. These volatiles, some of which may play a significant role in the interaction of the plant with the carrot root fly (Psila rosae), were analysed using gas chromatography/mass spectroscopy. The resulting chromatograms are arranged in order of embryo development. The progressive elaboration of the volatile profile reflects the increased biosynthetic capacity of the developing embryo. PMID- 24221847 TI - Multiple shoot production from seedling explants of slash pine (Pinus elliottii, Engelm.). AB - Hypocotylary explants obtained from 30- to 40-day-old slash pine (Pinus elliottii, Engelm.) seedlings treated with 6-benzylaminopurine produced multiple buds that eventually elongated into axillary shoots. The explants were pulse treated (45-s dip) with 6-benzylaminopurine (22.2, 111, 222 MUM) plus a control and cultured on three different basal media containing activated charcoal (0.5% w/v). Hormonal concentration and basal medium were compared for the number and size of axillary shoots induced after 12 and 29 days. The greatest number of axillary shoots was produced by explants that were pulse treated with 111 MUM 6 benzylaminopurine and cultured on Gresshoff and Doy medium. The axillary shoots were fewer in number per explant than shoots previously reported resulting from hormonally induced advantitious buds of slash pine, but the axillary shoots developed more rapidly. PMID- 24221848 TI - Changes in abscisic acid and its beta-D-glucopyranosyl ester levels during tomato (Lycopersicon esculentum Mill.) seed development. AB - The role of abscisic acid (ABA) in tomato (Lycopersicon esculentum Mill.) zygotic embryogenesis was analysed. ABA and ABA beta-D-glucopyranosyl ester (ABA-GE) changes were determined in seeds and fruit tissues - placenta and mesocarp - during seed development, which was defined with eight embryo stages: from globular (stage 1) to mature embryo (stage 8). In whole seeds, ABA changes paralleled fresh and dry weight pattern curves and could be characterized by a high increase during embryo growth followed by a decrease as the seed matured and dehydrated. Moreover this dehydration phase led, at stage 8, to a new ABA distribution within the seed, preferentially into integument and embryo. Fruit tissue analyses provided new information about the ABA origin in seeds. ABA-GE levels were also measured and the results suggested different ABA metabolism in seed and fruit tissues. PMID- 24221849 TI - In vitro selection and regeneration of cotton resistant to high temperature stress. AB - Cell suspension cultures of cotton (Gossypium hitirsutum L. cv. Coker 312) were exposed to various temperature:time treatments in order to select cell lines resistant to high temperature stress. Cells were exposed to 45 degrees C for 3 h each day until the total accumulated hours of stress were: 0 h, 10 h, 75 h, 100 h, or 105 h (81 h pulsed then 24 h continuous). After the stress treatments, the cells were plated onto embryo development medium and plants were recovered. The embryogenic calli that were recovered were subcultured monthly for 6 months and tested for increased resistance to the temperature:time treatments previously determined to be lethal and to water stress as imposed by PEG. All of the selected cell lines were more resistant to both types of stress than the control cell lines. Leaf tissue of stress selected (Ro) formed and maintained callus growth when incubated at 38 degrees C; whereas, tissue excised from nonselected controls rarely formed callus and calli which did form quickly became necrotic. These cells and plants will provide a tool for determining the mechanisms involved in resistance to high temperature stress. PMID- 24221850 TI - Plant regeneration via somatic embryogenesis in creeping bentgrass (Agrostis palustris Huds.). AB - We have established a high-frequency plant regeneration system via somatic embryogenesis from mature seeds of creeping bentgrass (Agrostis palustris Huds). The effects of 2,4-dichlorophenoxyacetic acid (2,4-D), 3.6-dichloroo-anisic acid (dicamba) and 6-benzyladenine (BA) on callus formation and embryogenesis were evaluated. Callus produced on the Murashige and Skoog (MS) (1962) medium containing 2,4-D had low embryogenic potency. In the presence of 30 MUM dicamba, addition of 2.25 to 9 MUM BA significantly enhanced embryogenic callus formation over dicamba alone. Optimum frequency of somatic embryogenesis was achieved on MS basal medium containing 30 MUM dicamba and 2.25 MUM BA. Over 80% of somatic embryos germinated and formed plantlets on half-strength MS basal medium. These plantlets grew normally in the greenhouse. PMID- 24221851 TI - In vitro propagation of Lilium testaceum and structural investigation of the storage beta-1,4-glucomannan. AB - Bulblet and callus cultures of Lilium testaceum were initiated in vitro from bulbscales. Continous propagation of the bulblet cultures was achieved on a modified Murashige and Skoog agar medium containing 1-naphthalene acetic acid (0.1 mg/l) and kinetin (0.1 mg/l) as phytohormones. The in vitro grown bulbs synthesized large quantities of storage beta-1,4-glucomannans (mannose: glucose = 7?3; molecular weight = 200 kd) with an identical structure to the glucomannans from the in vivo grown bulbs. Higher 1-naphthalene acetic acid concentrations (1 mg/l) resulted in increased callus formation. Liquid suspension cultures derived from callus exhibited only small amounts of reserve glucomannans. PMID- 24221852 TI - Callus induction in Phyllanthus species and inhibition of viral DNA polymerase and reverse transcriptase by callus extracts. AB - Studies on callus induction and growth in Phyllanthus amarus Schum. & Thonn. (Euphorbiaceae) and some related species are described, as well as the inhibition of enzymes of hepatitis B and related viruses by callus extracts. Callus was induced from stem or branch pieces of P. amarus placed on several media combinations. Optimum induction and growth of friable, undifferentiated calli occurred on Murashige and Skoog medium supplemented with either 0.5 mg or 1 mg of BA/liter and 1 mg/liter of either 2,4-D or IBA, but not IAA. Callus induction using the same media was also attempted with other Phyllanthus spp. The best success was with P. abnormis. Aqueous extracts from fieldgrown plants were more active in vitro against viral DNA polymerase and reverse transcriptase than extracts of calli. PMID- 24221853 TI - Long-term cultures of barley synthesize and correctly deposit seed storage proteins. AB - Long-term cultures of four different cultivars of barley (Hordeum vulgare L.) have been established. Both callus and suspension cultures formed embryogenic structures at high frequency even after more than 18 months of culture. These compact proembryogenic cell clusters synthesize seed storage globulins whereas loose cell aggregates in callus culture and suspension cultures of fine dispersed consistency were free of globulins. Globulin synthesis was especially intense in compact structures of callus cultures established from suspension culture-derived protoplasts. Within the cells storage globulins are deposited in the vacuolar compartment as in zygotic embryos. The molecular data provided recommend the system for studies on factors determining seed protein gene expression and intracellular protein transport. PMID- 24221854 TI - Adventitious bud regeneration from leaf expiants of the shrubby ornamental honeysuckle, Lonicera nitida Wils. cv. 'Maigrun': effects of thidiazuron and 2,3,5-triiodobenzoic acid. AB - Different combinations of auxins and cytokinins were employed to assess the regeneration capacity from in vitro leaf explants of Lonicera nitida Wils. cv 'Maigrun'. A high frequency of rhizogenesis was noticed, with 2.3 MUM thidiazuron plus 2.9 MUM indole-3-acetic acid as the only hormonal combination to support caulogenic responses. Increasing thidiazuron concentration and/or suppressing auxin did not improve caulogenesis. Combining thidiazuron with 2,3,5 triiodobenzoic acid produced a dramatic increase in the percentage of caulogenic explants. A maximum of 74% of adventitious bud forming explants was obtained with 2.3 MUM thidiazuron plus 20 MUM 2,3,5-triiodobenzoic acid. Buds were often in a rosette form and were vitreous, so that shoot elongation was difficult to obtain. The effect of the duration of the 2,3,5-triiodobenzoic acid treatment on shoot elongation was investigated. PMID- 24221855 TI - The gibberellin synthesis inhibitors, ancymidol and flurprimidol, promote in vitro rooting of white pine microshoots. AB - Ancymidol and flurprimidol were tested for their ability to induce in vitro rooting on axillary proliferated shoots of white pine (Pinus strobus L.). Shoots were treated for 30 days (pulse) with growth regulators, then subcultured to 0.5X medium for conifer morphogenesis without growth regulators. A pulse treatment containing 5 MUM ancymidol and 0.54 MUM naphthaleneacetic acid resulted in 43% rooted shoots, whereas a pulse treatment with 0.54 MUM naphthaleneacetic acid alone resulted in 7% root formation. Flurprimidol also stimulated rooting of white pine shoots, but was less effective than ancymidol. No detrimental effects on shoot growth were observed with the gibberellin synthesis inhibitors at the 5 MUM concentration used. Some rooted shoots were successfully acclimatized to the greenhouse. PMID- 24221856 TI - Plant regeneration from stem and petal of carnation (Dianthus caryophyllus L.). AB - Plants were regenerated via adventitious shoot initiation from petal explants of carnation (Dianthus caryophyllus L.) cultivars Crowley Sim, Ember Rose, Orchid Beauty, Red Sim, White Sim and from stem segments of Crowley Sim, Red Sim, White Sim. Differences in cultivar response were observed, with White Sim being the most responsive for both explant types. Plants were also regenerated from receptacles of this cultivar. The effect of different cytokinins on regeneration from petal and stem explants of cultivar White Sim was compared. Thidiazuron was more effective than 6-benzylaminopurine or kinetin. In stem explants, morphogenic capacity was determined by the developmental stage of the explant. Highest percentage of shoot formation was observed in the youngest stem segments, on all the cytokinins tested. Stem-derived plants grew faster than petal or receptacle derived plants and produced normal, flowering plants eight to ten months after culture. PMID- 24221857 TI - Could extreme emotional stress be a potential precipitating factor associated with posterior reversible encephalopathy syndrome in postpartum woman? A case report. PMID- 24221858 TI - Validation of the Italian version of Parkinson's disease-cognitive rating scale (PD-CRS). AB - Cognitive impairment (CI) is a frequent feature associated with both early and advanced stages of Parkinson's disease (PD). An evaluation of cognitive functions is relevant to identify those parkinsonians at risk of developing dementia. In the present study, the Italian version of Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assessing fronto-subcortical and cortical cognitive functions in PD was validated in 387 parkinsonians and was used to test the empirical validity of the item 1.1 (cognitive impairment) of the Italian version of MDS-UPDRS as screening tool for CI in PD. PD-CRS was free from floor and ceiling effect. The mean PD-CRS score was 76.1 (mean cortical score, 24.5 +/- 4.6; mean subcortical score, 51.5 +/- 17.5). The internal consistency was satisfactory (alpha = 0.89); corrected item-total correlation was 0.570 (naming) to 0.696 (working memory). The correlation between PD-CRS and part I-IV of MDS-UPDRS was weak. The low agreement between classification of PD sample into patients with mild cognitive impairment (PD-MCI), dementia (PD-D) and normal cognition (PD-NC) according to scores of item 1.1 and classification according to cutoff scores of PD-CRS for PD MCI, PD-D and PD-NC indicated a poor empirical validity of item 1.1 of MDS-UPDRS as cognitive screening tool for CI in PD (Kappa = 0.114; weighted Kappa = 0.17; SE of Kappa = 0.038; 95 % confidence interval from 0.040 to 0.1895). The Italian version of PD-CRS is an easy, consistent and valid tool for assessment of the cognitive cortical and subcortical impairments in PD. PMID- 24221859 TI - The effects of BMSCs transplantation on autophagy by CX43 in the hippocampus following traumatic brain injury in rats. AB - Traumatic brain injury (TBI) can initiate a series of complicated pathological events, and induce various types of neuronal cell death including autophagy and apoptosis. Currently, the treatment of TBI is one of the main challenges in neurobiology. In this regard, the administration of bone marrow stromal cells (BMSCs) represents a novel treatment modality for TBI. However, the protective mechanism of BMSCs was unknown in the TBI. The aim of the present study was to assess the effects of BMSCs on connexin 43(CX43) and autophagy in the hippocampus following TBI in rats. A rat model of TBI was created using a modified weight drop device. Double-membrane structures in the process of autophagy formation were frequently observed in injured brain by electron microscopy. The levels of autophagic pathway associated proteins and CX43 were also detected by western blot analysis. Specifically, immunoblotting results showed that BMSCs treatment after TBI could down-regulate light chain 3 (LC3), Beclin-1 and CX43 expression in the hippocampus. Taken together, our results demonstrated that BMSCs were able to significantly suppress TBI-induced autophagy activity, and the potential mechanism by regulating CX43 levels. PMID- 24221860 TI - Dr Junkie. The Doctor Addict in Bulgakov's Morphine: What are the Lessons for Contemporary Medical Practice? AB - Historical, cultural and professional factors have contributed to stigma and secrecy regarding addiction in the medical profession and there are calls to improve education in this area. This paper argues that physician-penned literature plays an important role in raising awareness of substance misuse in the medical profession. Bulgakov's short story Morphine documents the decline of Dr Polyakov and illustrates a number of salient professional issues such as self medication, abuse of authority and risks to patients. Physician-penned literature such as Morphine is of value in medical education as it offers a route into sensitive topics and an authoritative and insider perspective that is attractive to students and physicians alike. PMID- 24221861 TI - Airs, waters and places. PMID- 24221862 TI - Evaluation of potential topsoil productivity. AB - A biomass productivity model based on soil properties and climate is developed from literature and used to evaluate and compare potential effects of mining and reclamation on several soils in the continental United States. Soil productivity is assumed to vary as a product of root distribution function modified by five soil properties: available water, aeration porosity, bulk density, electrical conductivity, and pH. Yield limiting property levels are derived from literature and input soil data are obtained from available USDA Soil Conservation Service information on typical profiles. Modelled values of potential productivity after mining, indicate problems and limitations to be expected. The proposed model can be used as a guide to reclamation strategy, to restore the land to premining conditions, or at times to enhance productivity of a reclaimed area. PMID- 24221863 TI - Analysis of the effects of zinc pollution on the macro-invertebrate populations of the Afon Crafnant, North Wales. AB - The study of the input draining from mine-waste into the Afon Crafnant, N. Wales, revealed that the most significant pollutant was zinc. The concentrations of zinc were monitored during 1978 and 1979, and spot samples were concentrated and analysed for lead, copper, cadmium, iron, cobalt, manganese and nickel. Analysis was by flame atomic absorption specto-scopy. The 'total' zinc concentration of the input was about 4 mg Zn/l which was diluted by the Afon Crafnant to give mean annual concentrations of 213 MUg Zn/l and 146 MUg Zn/l for 1978 and 1979 respectively at a site 60 metres downstream of the input. The numbers of individuals and number of taxa in the macro-invertebrate community were reduced at these concentrations. The taxa affected werePhagocata vitta,Erpobdella octoculata, Oligochaeta,Ithytrichia lamellaris, Simuliidae,Ancylus fluviatilis andRithrogena semicolorata. Several commonly used diversity indices failed to show differences between the macro- invertebrate communities at the affected and control sites whereas a modified version of Chandler's Biotic Score (detailed in this paper) revealed both the acute effects at higher concentrations and the chronic effects at lower concentrations. PMID- 24221864 TI - Effects of initial irrigation, seeding date and directlyhauled topsoil on mined land community composition. AB - This study was implemented to determine the effects of one, two, or three months of establishment irrigation, after spring or summer seeding on the long-term composition of mined land plant associations. While the treatment plots were seeded with the same diverse mixture of native species, floristic differences among treatment combinations were apparent after five growing seasons. Summer seeding enhanced the development of seeded warm-season grasses by retarding the initial development of seeded cool-season grasses and by limiting competitive effects of nonseeded species through seedbed tillage. Supplemental irrigation was substantially more important to the development of warm- than cool-season grasses. Seeded perennial forbs performed poorly on all treatments, presumably due to low seed viability, low germination, and/or competition from more water responsive species. Despite drought conditions during plant establishment, supplemental irrigation was not critical to the ultimate development of nonseeded plant species when seedbed tillage occurred shortly after topsoil was applied. However, irrigation became more important to the long-term development of these species when tillage was delayed. Most forbs encountered were perennial natives that had volunteered from the direct-haul topsoil.Atriplex canescens was the only successful seeded shrub and performed particularly well on the summer seeded plot that received one month of initial irrigation. PMID- 24221865 TI - Determining conservation priorities. AB - One important component in achieving an optimal compromise between mineral development and environmental conservation is to rank different geographical areas according to their priorities for development and conservation respectively. The latter is considered here.There are three main steps in assigning conservation priorities: (i) acquisition and assessment of information on the existing baseline environment and on potential impacts; (ii) assignment of values to the environmental components concerned and integration of these to yield overall values for alternative possible conservation targets; and (iii) incorporation of logistic considerations to determine the practical priorities for conservation.One particularly critical aspect of this process is the relative significance of different conservation criteria, specifically including the presence of rare species, high diversity, pristine condition and representativeness. These criteria all reflect the same underlying conservation values, but their relative significance varies from case to case. Their integration is based on professional judgement rather than any formal algorithm and explicit guidelines for such judgement are needed to promote consensus in the determination of conservation priorities. PMID- 24221866 TI - Immunocytochemical localization of cytokinins in Craigella tomato and a sideshootless mutant. AB - Post-embedding immunocytochemical techniques using peroxidase-antiperoxidase or immunoglobulin G-gold as markers were used for the localization of cytokinins (CKs) in two isogenic lines, Craigella (C) and Craigella lateral suppressor (Cls), of tomato Lycopersicon esculentum Mill. Terminal buds, nodes, hypocotyl segments and root tips were submitted to a periodate-borohydride procedure, to obtain the coupling of isopentenyladeosine and zeatin riboside to cellular proteins, followed by a fixative step with a paraformaldehyde and glutaraldehyde mixture. Enzyme-linked immunosorbent assay tests performed on ovalbumin-coated microtitration plates have shown that this method was effective for CK riboside and base coupling to proteins. Paraffin-wax- or Spurr's-resin-embedded sections were cleared of wax or resin before incubation with anti-zeatin riboside or anti isopentenyladenosine antibodies. The procedure was thoroughly investigated and many controls were done in order to eliminate artefacts. The immunostaining patterns observed along the plants showed a basipetally decreasing gradient of CKs along the stem and in the roots. Immunolabelling was higher in the actively growing regions of the stem bud and root apices. Terminal buds of Cls appeared to be less immunoreactive than C, whereas no differences were detected in root-tip immunolabelling. The staining patterns are consistent with the idea that root and bud apices have a different CK metabolism. The absence of axillary bud formation in Cls is correlated with low CK levels in the organogensis sites. PMID- 24221867 TI - Growth kinetics of the Golgi apparatus during the cell cycle in onion root meristems. AB - In onion root meristems, the number of dictyosomes per cell shows a kinetics of growth strongly related to the cell cycle. During the interphase of steady-state proliferative cells, the volume density and numerical density of the Golgi apparatus decrease to reach minimum values in late-interphase cells, characterized by their greatest length. This pattern is also found in the total volume occupied by Golgi apparatus. Once in mitosis, the above-mentioned parameters begin to increase reaching maximum mean values in telophase. After the experimental uncoupling of chromosome and growth cycles by presynchronization with hydroxyurea, we found a similar behaviour pattern in the Golgi apparatus: decreasing values during interphase and a triggering of Golgi-apparatus growth in prophase independently of the bigger cell sizes reached in mitosis as an effect of pretreatment with hydroxyurea. These results indicate a cyclic kinetics of this subcellular component in higher-plant meristems, coupled with early mitotic events. PMID- 24221868 TI - Extracellular ice and cell shape in frost-stressed cereal leaves: A low temperature scanning-electron-microscopy study. AB - Low-temperature scanning electron microscopy was used to examine transverse fracture faces through cereal leaf pieces subjected to frost. Specimens were studied before and after sublimation of the ice. The position of extracellular ice in the leaf was inferred from the difference between the specimen before and after sublimation and from ridges and points which occurred in the extracellular ice during sublimation. Steps in the fracture surface indicated that the fracture plane passed through the extracellular ice crystals as well as through cells and also helped identify extracellular ice. The cells in controls were turgid and extracellular ice was absent. Leaf pieces from hardened rye were excised and frost-stressed to-3.3 degrees ,-21 degrees and-72 degrees C, cooling at 2-12 degrees .h(-1). Cell collapse and extracellular ice were evident at-3.3 degrees C and increased considerably by-21 degrees C. At-21 degrees and-72 degrees C the leaf pieces were mainly filled with extracellular ice and there were few remaining gas spaces. The epidermal and mesophyll cells were laterally flattened, perpendicular to their attachment to adjacent cells, and phloem and vascular sheath cells were more irregularly deformed. Leaf pieces from tender barley were cooled at 2 degrees C.min(-1) to-20 degrees C; they were then mainly filled with extracellular ice, and the cells were highly collapsed as in the rye. In rye leaves frozen to-3.6 degrees C before excision, ice crystals occurred in peri vascular, sub-epidermal and intervening mesophyll spaces. In rye leaf pieces frozen to-3.3 degrees C after excision or to-3.6 degrees C before excision, mesophyll cells were partly collapsed even when not covered by ice, indicating that collapse of the cell wall, as well as the enclosed protoplast, was driven by dehydration. No gas or ice-filled spaces were found between wall and the enclosed protoplast. It is suggested that this can be explained without invoking chemical bonding between cell wall and plasma membrane: when the wall pores are filled by water, the pore size would reduce vapour pressure so making penetration of the wall by ice or gas less likely. PMID- 24221869 TI - Abscisic acid and water transport in sunflowers. AB - The role of abscisic acid (ABA) in the transport of water and ions from the root to the shoot of sunflower plants (Helianthus annuus) was investigated by application of ABA either to the root medium or to the apical bud. The exudation at the hypocotyl stump of decapitated seedlings was measured with and without hydrostatic pressure (0-0.3 MPa) applied to the root. All ABA concentrations tested (10(-10)-10(-4) mol.l(-1)) promoted exudation. Maximal amounts of exudate (200% of control) were obtained with ABA at 10(-6).mol.l(-1) and an externally applied pressure of 0.1 MPa. The effect was rapid and long-lasting, and involved promotion of ion release to the xylem (during the first hours) as well as an increase in hydraulic conductivity. Abscisic acid applied to the apical bud had effects similar to those of the rootapplied hormone. Increased rates of exudation were also obtained after osmotic stress was applied to the root; this treatment increased the endogenous level of ABA in the root as well as in the shoot. Water potentials of the hypocotyls of intact plants increased when the roots were treated with ABA at 5 degrees C, whereas stomatal resistances were lowered. The results are consistent with the view that ABA controls the water status of the plant not only by regulating stomatal transpiration, but also by regulating the hydraulic conductivity of the root. PMID- 24221870 TI - Purification and properties of nitrite reductase from roots of pea (Pisum sativum cv. Meteor). AB - Nitrite reductase (EC 1.6.6.4) prepared from pea roots was found to be immunologically indistinguishable from pea leaf nitrite reductase. Comparisons of the pea root enzyme with nitrite reductase from leaf sources showed a close similarity in inhibition properties, light absorption spectrum, and electron paramagnetic resonance signals. The resemblances indicate that the root nitrite reductase is a sirohaem enzyme and that it functions in the same manner as the leaf enzyme in spite of the difference in reductant supply implicit in its location in a non-photosynthetic tissue. PMID- 24221871 TI - Cell specificity in auxin- and ethylene-induced 'supergrowth' in Riella helicophylla. AB - In gemmalings of Riella helicophylla, auxin and ethylene stimulate elongation growth, especially of pillar cells. When the two hormones are supplied simultaneously, the effects are additive, i.e. the result is 'supergrowth'. In the cells of the meristem, elongation is enhanced by auxin, but not by ethylene when given alone. However, these cells also respond with 'supergrowth' to a combined treatment with auxin and ethylene. The antiauxin p chlorophenoxyisobutyric acid suppresses both the ethylene stimulation of cell growth and the additive 'supergrowth'. The results support the concept that auxin pre-conditions the cells to the ethylene-dependent growth event. We suggest that the response elicited by the specific cell types could be related to differences in their level of endogenous auxin. PMID- 24221872 TI - Temperature-dependent feedback inhibition of photosynthesis in peanut. AB - Arachis hypogaea L. is a tropical crop that is slow-growing at temperatures below 25 degrees C. Unadapted CO2-assimilation rate (A) showed insufficient variation between 15 and 30 degrees C in the short term (hours) to explain this marked reduction in growth. However, at longer periods (12 d), A was depressed as were growth rate and leafproduction rate. To examine the possible relationship between growth, A and sink demand plants were transferred from 30 degrees C, which is near the optimum for growth, to a suboptimal temperature (19 degrees C). In the first 2 d of cooling, A decreased by 50-70%, the stomata stayed open, and the intercellular CO2 concentration (ci) rose, i.e. the decrease in A of the cooled plants was the result of non-stomatal factors. Changes in dark respiration did not account for the decline in A.Clear evidence was obtained of sink control of A by independently manipulating the temperature of different leaves on the plant. Cooling (to 19 degrees C) most of the plant (the sink) led to a 70% decline in A of the remaining leaves at 30 degrees C after 3 d, whereas the converse treatments (30 degrees C sink, 19 degrees C source) resulted in small changes (17%). In plants at 19 degrees C which were exposed to low CO2 concentration to prevent photosynthesis, A was not reduced when measured at normal CO2 concentrations, indicating that carbohydrate accumulation was responsible for the decline in A. Dry-matter build-up at suboptimal temperature was also consistent with end-product inhibition of photosynthesis. PMID- 24221873 TI - Photoinhibition of photosynthesis in intact kiwifruit (Actinidia deliciosa) leaves: Effect of light during growth on photoinhibition and recovery. AB - Photoinhibition of photosynthesis was induced in intact kiwifruit (Actinidia deliciosa (A. Chev.) C. F. Liang et A. R. Ferguson) leaves grown at two photon flux densities (PFDs) of 700 and 1300 MUmol.m(-2).s(-1) in a controlled environment, by exposing the leaves to PFD between 1000 and 2000 MUmol.m(-2).s( 1) at temperatures between 10 and 25 degrees C; recovery from photoinhibition was followed at the same range of temperatures and at a PFD between 0 and 500 MUmol.m(-2).s(-1). In either case the time-courses of photoinhibition and recovery were followed by measuring chlorophyll fluorescence at 692 nm and 77K and by measuring the photon yield of photosynthetic O2 evolution. The initial rate of photoinhibition was lower in the high-light-grown plants but the long term extent of photoinhibition was not different from that in low-light-grown plants. The rate constants for recovery after photoinhibition for the plants grown at 700 and 1300 MUmol.m(-2).s(-1) or for those grown in shade were similar, indicating that differences between sun and shade leaves in their susceptibility to photoinhibition could not be accounted for by differences in capacity for recovery during photoinhibition. Recovery following photoinhibition was increasingly suppressed by an increasing PFD above 20 MUmol.m(-2).s(-1), indicating that recovery in photoinhibitory conditions would, in any case, be very slow. Differences in photosynthetic capacity and in the capacity for dissipation of non-radiative energy seemed more likely to contribute to differences in susceptibility to photoinhibition between sun and shade leaves of kiwifruit. PMID- 24221874 TI - Purification of GP57, and auxin-regulated extracellular glycoprotein of carrots, and its immunocytochemical localization in dermal tissues. AB - A glycoprotein (GP57) was purified by ion-exchange and hydroxylapatite column chromatography from the 70%-ethanol precipitate of culture medium of non embryogenic carrot cells (Daucus carota L.) grown with 2,4-dichlorophen-oxyacetic acid (2,4-D). Its apparent molecular mass (M r) was estimated to be 57000 by sodium dodecylsulfate-polyacrylamide gel electrophoresis and 50000 by gel filtration. GP57 contained 14% (w/w) carbohydrate; the M r of the peptide portion was estimated to be 55000 after deglycosylation by trifluoromethanesulfonic acid. GP57 is composed of two polypeptides with the same Mr and with very similar amino acid composition but different pI values, 8.8 and 9.5. Both are rich in aspartic acid, serine and threonine, and may possess N-linked oligosaccharide chains, including fucose and xylose. A monoclonal antibody (MAb) against the purified GP57 reacted with both the pI 8.8 and the 9.5 components, as well as the deglycosylated GP57. Immunoblotting with the MAb indicated that GP57 is synthesized in and released from cultured cells which have been supplied with auxin. In immunocytochemical studies, GP57 was found in the space between the embryo and the endosperm of dry seeds, and its content decreased during germination. GP57 was also found in the endodermis and epidermis of young roots, the periderm of mature taproots, and the epidermis of petioles and young leaves. PMID- 24221875 TI - Acclimation of photosynthesis in Zea mays to low water potentials involves alterations in protoplast volume reduction. AB - Effects of water-stress treatment of Zea mays L. plants on protoplast volume and photosynthesis in leaf slices exposed to solutions of different osmotic potential (Psi s) were studied. Decreased photosynthetic capacity in the leaf slices at low tissue Psi w was associated with dehydration-induced protoplast-volume reduction. Leaf slices from plants exposed to in-situ water deficits exhibited greater photosynthetic capacity and relative protoplast volume at low water potential (Psi w) invitro than tissue from control plants.In-situ water stress induced osmotic adjustment of the leaf tissue as determined by pressure/volume analysis. It is concluded that plant acclimation to low leaf Psi w may involve a reduced degree of cell shrinkage at a given Psi w. This acclimation would allow for the maintenance of relatively higher photosynthetic capacity at low water protentials. PMID- 24221876 TI - Pectins as mediators of wall porosity in soybean cells. AB - The non-invasive technique of fluorescence redistribution after photobleaching was employed on soybean (Glycine max (L.) Merr.) root cells grown in suspension culture to examine macromolecular transport across plant cell walls. Using both fluorescently derivatized dextrans and proteins of graded size, a functional range of diameters for putative trans-wall channels was determined to be 6.6-8.6 nm. A mild treatment with pectinase apparently enlarged the channels, without adversely affecting cell viability, enabling significantly larger molecules to pass through the wall. Treatment of the cells with cellulysin or protease did not have this enlargement effect. It appears that the organization of pectic substances is a major control element in defining the sieving properties of the wall. PMID- 24221877 TI - Enrichment for Nicotiana heterokaryons after protoplast fusion and subsequent growth in agarose microdrops. AB - Protoplasts isolated from Nicotiana tabacum L. leaves and Nicotiana suaveolens Lehm. cell suspensions have been fused with polyethylene glycol (PEG). Enrichment for heterokaryons was based on a Percoll flotation protocol which allowed a preparation with 50% heterokaryons to be obtained. The heterokaryons developed into calli whose hybrid nature was shown by polyacrylamide gel electrophoresis of esterase isoenzymes. Sensitivity of the mesophyll protoplasts to PEG and different buoyant densities of the heterokaryon and cell-suspension protoplasts contribute to the enrichment. The 50%-fusion figure following purification is an improvement on standard PEG procedures.Heterokaryons obtained were embedded in 20MUl drops of agarose and placed in a liquid nurse culture that allows optimum growth of the heterokaryons and maintains a physical boundary between the heterokaryons and the nurse culture. Once colonies develop, the agarose microdrop is removed from the nurse culture and placed on shoot-induction medium. Agarose microdrops containing the heterokaryons can be readily removed at any stage and processed for electron microscopy to follow the early stages of colony development.The procedures we have utilised provide a robust physical selection method that allows the total variation from a heterokaryon population to be expressed. PMID- 24221878 TI - Arrangement of cortical microtubules in the shoot apex of Vinca major L. : Observations by immunofluorescence microscopy. AB - The arrangements of cortical microtubules (MTs) and of cellulose microfibrils in the median longitudinal cryosections of the vegetative shoot apex of Vinca major L., were examined by immunofluorescence microscopy and polarizing microscopy, respectively. The arrangement of MTs was different in the various regions of the apex: the MTs tended to be arranged anticlinally in tunica cells, randomly in corpus cells, and transversely in cells of the rib meristem. However, in the inner layers of the tunica in the flank region of the apex, cells with periclinal, oblique or random arrangements of MTs were also observed. In leaf primordia, MTs were arranged anticlinally in cells of the superficial layers and almost randomly in the inner cells. Polarizing microscopy of cell walls showed that the arrangement of cellulose microfibrils was anticlinal in tunica cells, random in corpus cells, and transverse in cells of the rib meristem; thus, the patterns of arrangement of microfibrils were the same as those of MTs in the respective regions. These results indicate that the different patterns of arrangement of MTs and microfibrils result in specific patterns of expansion in the three regions. These differences may be necessary to maintain the organization of the tissues in the shoot apex. PMID- 24221879 TI - Inhibition of auxin-stimulated growth of pea stem segments by a specific nonasaccharide of xyloglucan. AB - Hemicellulose extracted from cell walls of suspension-cultured rose (Rosa "Paul's Scarlet") cells was digested with cellulase from Trichoderma viride. The quantitatively major oligosaccharide products, a nonasaccharide and a heptasaccharide derived from xyloglucan, were purified by gel permeation chromatography. The nonasaccharide was found to inhibit the 2,4-dichlorophenoxy acetic-acid-induced elongation of etiolated pea (Pisum sativum) stem segments. This confirms an earlier report (York et al., 1984, Plant Physiol. 75, 295-297). The inhibition of elongation by the nonasaccharide showed a maximum at around 10( 9)M with higher and lower concentrations being less effective. The heptasaccharide did not significantly inhibit elongation at 10(-7)-10(-10)M and also did not affect the inhibition caused by the nonasaccharide when co-incubated with the latter. PMID- 24221880 TI - Improved somatic embryogenesis in wheat by partial simulation of the in-ovulo oxygen, growth-regulator and desiccation environments. AB - The effects of O2, growth-regulators and desiccation on callus growth and somatic embryo (embryoid) development were investigated in cultures of immature embryos of two lines of Triticum aestivum L. Callus and embryoid formation were induced on media that contained N(6)-furfurylamin-opurine (kinetin) and either 2,4 dichlorophenoxyacetic acid or 3,6-dichloro-o-anisic acid, either with or without abscisic acid (ABA). Cultures containing differentiated embryoids were then exposed to high concentrations of both ABA and indole-3-acetic acid, after which samples were desiccated to approx. 10% tissue moisture. Incubating cultures in 3.2 mmol.l(-1) O2 (approx. 9%, low-O2) increased embryoid formation sixfold in one wheat line and nearly threefold in another. In the former line low-O2 caused the formation of mostly embryogenic callus. Low-O2 also decreased precocious germination of immature embryos, decreased callus growth, and improved development and viability of the resultant embryoids. Including 1.9 MUmol.l(-1) ABA in the callus-induction medium reduced germination of immature embryos and reduced the incidence of embryoids with visible abnormalities. Despite the improved morphology, significantly fewer of the embryoids produced on ABA containing medium germinated. Desiccation significantly enhanced germination of these embryoids as well as those produced on ABA-free medium. PMID- 24221881 TI - Amyloplast development in etiolated and ethylene-treated pea epicotyls. AB - The amyloplasts found in the apical hook cells of etiolated pea (Pisum sativum L.) epicotyls were randomly distributed. Sedimentation of endodermal amyloplasts in the direction of gravity became apparent in the transition from the hook to the top of the main axis of the epicotyl. Cortical amyloplasts in this region were not, however, sedimented. These patterns of sedimentation could not be related to changes in amyloplast size, and it is proposed that cytoplasmic properties determine amyloplast behaviour.The differentiation of plastids in the hook differed between the amyloplast-containing endodermal cells and the cortical cells, in which amoeboid plastids predominated over amyloplasts. Amyloplasts disappeared from the cortical cells in the main axis of the epicotyl, but in the endodermal cells sedimented amyloplasts were found throughout the upper epicotyl.Etiolated epicotyls induced to grow horizontally by treatment with ethylene had a normal content of amyloplasts, sedimented in the direction of gravity. PMID- 24221882 TI - Autonomic dysfunction of overweight combined with low muscle mass. AB - OBJECTIVE: To examine the relationship between overweight combined with low muscle mass and the cardiac autonomic nervous system using heart rate variability (HRV) in healthy workers. METHODS: A total of 1,150 workers were included, with a mean age of 43.55 +/- 11.45 years. The subjects were classified as low muscle mass if their appendicular skeletal muscle mass was below the 50th percentile of the study sample. Similarly, subjects were classified as overweight if their body mass index was above 25 kg/m(2). Electrocardiography recordings were obtained for 5 min, and the time-domain and frequency-domain indices of HRV were analyzed. RESULTS: Compared with the high muscle mass and non-overweight (HMM) group, the low-frequency power and the standard deviation of normal-to-normal intervals were significantly decreased in both the overweight and high muscle mass (OHMM) group and the overweight and low muscle mass (OLMM) group. The significantly decreased high-frequency (HF) power and square root of the mean squared differences of successive differences, which reflects efferent parasympathetic activity, was indicative of reduced parasympathetic modulation in the OHMM and OLMM groups. In addition, the OLMM group had a lower HF power than did the OHMM group. CONCLUSIONS: This study suggests that HRV is reduced in overweight combined with low muscle mass group than overweight and HMM group. PMID- 24221883 TI - Acaricide activity of different extracts from Piper tuberculatum fruits against Rhipicephalus microplus. AB - Rhipicephalus microplus is the main tick that affects cattle. Plant bioactive molecules can be used to control this ectoparasite. The aim of this study was to evaluate the in vitro efficacy of Piper tuberculatum fruit extracts obtained with different solvents on R. microplus larvae and engorged females. Hexane, ethyl ether, ethanolic, and methanolic extracts of P. tuberculatum fruits were evaluated. After extraction, all of the extracts were dried. Adult immersion tests and larval packet tests were performed with five different concentrations of each of the extracts. The hexane extracts of P. tuberculatum showed the highest larvicidal activity against R. microplus (lethal concentration (LC50 = 0.04 mg/mL), followed by the ethyl ether (LC50 = 0.08 mg/mL), ethanolic (LC50 = 2.73 mg/mL), and methanolic (LC50 = 4.49 mg/mL) extracts. The P. tuberculatum fruit extracts were also effective against R. microplus-engorged females. Ethyl acetate extracts showed the highest efficiency (LC50 = 18.4 mg/mL), followed by the methanolic (LC50 = 105.6 mg/mL), ethanolic (LC50 = 140.0 mg/mL), and hexane (LC50 = 297.4 mg/mL) extracts. All of the extracts showed similar chromatographic profiles containing 24% piperine. The P. tuberculatum fruit extracts contain bioactive compounds with great potential to improve the standard formulations of acaricides for the control of R. microplus. PMID- 24221884 TI - Molecular characterization of voltage-gated calcium channel beta-subunits of Clonorchis sinensis. AB - The voltage-gated Ca(2+) channel beta-subunit is a member of the membrane associated guanylate kinase family and modulates kinetic properties of the Ca(2+) channels, such as their voltage-dependent activation and inactivation rates. Two cDNA clones were identified to encode each beta-subunit isotype of the voltage gated Ca(2+) channel of Clonorchis sinensis, CsCavbeta1 and CsCavbeta2, which consist of 606 and 887 amino acids, respectively. CsCavbeta1 was found to be similar to the beta-subunit containing two conserved serine residues that constitute the consensus protein kinase C phosphorylation site in the beta interaction domain (BID). CsCavbeta2 had cysteine and alanine residues instead of the two serine residues conserved in BID and was homologous to variant beta subunit of Schistosoma mansoni and Schistosoma japonicum. CsCavbeta1 and CsCavbeta2 were almost equally expressed in the adults and metacercariae, but were more expressed in adult C. sinensis than in metacercariae. Collectively, our findings suggest that substitution of the two serine residues in BID of CsCavbeta2 may render C. sinensis sensitive to praziquantel. PMID- 24221885 TI - Comparison between two commercially available serological tests and polymerase chain reaction in the diagnosis of Cryptosporidium in animals and diarrhoeic children. AB - For the detection of Cryptosporidium species in 804 animals and 165 diarrhoeic children (<10 years) in Egypt, two copro-antigen tests, the RIDASCREEN(r) Cryptosporidium test [enzyme immunoassay (EIA)] and the RIDA(r)QUICK Cryptosporidium/Giardia Combi [immuno-chromatographic test (ICT)] as well as polymerase chain reaction (PCR) were used. Prevalence of Cryptosporidium was 15.0, 19.5 and 32.3% in animals and 2.4, 6.7 and 49.1% in children using EIA, ICT and PCR, respectively.Using PCR as reference method, animal samples sensitivity (Se) of the EIA was 46.5% when questionable samples were considered positive, whereas specificity (Sp) was 100%. Se of the ICT was 60.4% while Sp was 100%. Positive predictive values (PPVs) for both EIA and ICT test were 100%, and negative predictive values (NPVs) for EIA were 79.7 and 84.1% for ICT. For the children samples, the Se of EIA was 5%, Sp was 100%, PPV was 100% and NPV was 52.2%, while the Se of ICT was 13.6%, Sp was 100%, PPV was 100% and NPV was 54.6%.The Kappa score of agreement between PCR and ICT was 67.4%, 54.1% between PCR and EIA and 84.4% between ICT and EIA. Until the second serial dilution of the EIA and ICT test, 9 * 10(3) oocysts/MUl of Cryptosporidia was detected, whereas in PCR, they were detected until the sixth serial dilution. Copro-antigen tests were easy to perform and less time-consuming but less sensitive compared to PCR. They obviously are best applicable for screening and epidemiological studies of large numbers of subjects, for batch specimen processing and in isolated or rural areas where reliable tests like PCR are unfeasible. When in children, a single stool sample is used for the diagnosis of clinical cases; better results can be obtained when non-standardized PCR due low specificity is coupled with copro-antigen tests. PMID- 24221886 TI - Dietary selenium affects intestinal development of Eimeria papillata in mice. AB - Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The prepatent period lasts for 3 days, but the course of infections varied. At Se-adequate diet, the maximum fecal output of oocysts amounted to 68,300 ooccysts/g feces on day 5 p.i.. However, fecal shedding of oocysts was accelerated in mice on Se-deficient diet and occurred already on day 4 p.i.. By contrast, maximal shedding is impaired in mice on high-Se diet, which takes place on day 5 p.i., but with a decreased output of only 7,300 oocysts/g feces. Light microscopy reveals that all developmental stages are affected: meronts, micro- and macrogamonts, and developing oocysts are increased in comparison with mice fed on selenium-adequate diet. At high Se, the number of parasitic stages in the jejunum is substantially higher than at Se deficient diet. Se does not affect the number of jejunal Alcian blue-stained goblet cells. Se deficiency increased the number of apoptotic cells in the jejunum. Substantially increased histological injury scores reveal more injuries in jejunum tissue infected by E. papillata. Our data indicate that high dietary Se exerts potential anticoccidial activity. This may be taken advantage of in control measures towards Eimeriosis as a feed additive, potentially alleviating the need for concomitantly utilized anti-coccidial drugs in the feed. PMID- 24221887 TI - The prevalence of Echinococcus multilocularis in red foxes in Poland--current results (2009-2013). AB - The aim of the study was to determine the prevalence of Echinococcus multilocularis in red foxes (Vulpes vulpes) in Poland. Overall, 1,546 intestinal samples from 15 of the 16 provinces in Poland were examined by the sedimentation and counting technique (SCT). The mean prevalence of E. multilocularis in Poland was 16.5% and was found in 14 of the 15 examined provinces. The mean intensity of infection was 2,807 tapeworms per intestine. Distinct differences in prevalence were observed between regions. In some provinces of eastern and southern Poland, the level of prevalence was 50.0% (Warminsko-Mazurskie), 47.2% (Podkarpackie), 30.4% (Podlaskie) and 28.6% (Malopolskie), while in other provinces (west and south-west), only a few percent was found: 2.0% (Dolnoslaskie), 2.5% (Wielkopolskie) and 0.0% (in Opolskie). The border between areas with higher and lower prevalence seems to coincide with a north-south line running through the middle of Poland, with prevalence from 17.5 to 50.0% in the eastern half and from 0.0 to 11.8% in the western half. The dynamic situation observed in the prevalence of this tapeworm indicated the necessity of continuing to monitor the situation concerning E. multilocularis in red foxes in Poland. PMID- 24221888 TI - A field survey for Wolbchia and phage WO infections of Aedes albopictus in Guangzhou City, China. AB - Wolbachia are maternal endosymbiotic bacterium, which infect a diverse range of arthropods, ranging from 20 to 76% in nature. They are capable of inducing a wide range of reproductive abnormalities to their hosts, such as cytoplasmic incompatibility (CI), which has been proposed to be used as a tool to modify mosquitoes that are resistant to the development of pathogen, as an alternative vector control strategy. Here, we evaluated the prevalence of Wolbachia and phage WO infections in the field population of Aedes albopictus in Guangzhou City via polymerase chain reaction (PCR) assay using the Wolbachia specific Wolbachia surface protein (wsp) and phage WO orf7 gene primers. Based on the results of PCR and phylogeny analysis, we found that A. albopictus in Guangzhou City were infected with two Wolbachia strains, wAlbA and wAlbB. Phage WO, the virus infected Wolbachia, was also detected in A. albopictus. One hundred and ten female individuals were screened via PCR, with 109 super-infected with Wolbachia and one sample single-infected with wAlbB strain. And 104 of 113 male individuals were both infected with wAlbA and wAlbB, and nine male samples were found to be infected with wAlbA strain only. The infection rates of phage WO in female and male individuals were 82.73 and 46.02%, respectively. These results showed that the natural Wolbachia and phage WO infections in A. albopictus population in Guangzhou were at a higher frequency at present, indicating that Wolbachia appear to be a better candidate nature resource for biological control insect vectors to reduce vector-borne diseases. PMID- 24221889 TI - In vitro acaricidal efficacy of plant extracts from Brazilian flora and isolated substances against Rhipicephalus microplus (Acari: Ixodidae). AB - The tick Rhipicephalus microplus causes significant losses in livestock cattle and has developed increasing resistance to the primary acaricides that are used to treat these infections. The objective of this study was to identify new biomolecules or isolated substances showing acaricidal activity from plants. Larval packet tests were conducted to evaluate the effects of 11 species of plants and three isolated substances (betulinic acid, eugenol, and nerolidol) on R. microplus. An adult female immersion test was performed with the substance that showed the highest larvicidal activity, which was evaluated for inhibition of reproduction. Tests using Licania tomentosa, Hymenaea stigonocarpa, Hymenaea courbaril, Stryphnodendron obovatum, Jacaranda cuspidifolia, Jacaranda ulei, Struthanthus polyrhizus, Chrysobalanus icaco, Vernonia phosphorea, Duguetia furfuracea, and Simarouba versicolor extracts as well as the isolated substance betulinic acid indicated lower acaricidal effects on R. microplus larvae. The extract displaying the best larvicidal activity was the ethanolic extract from L. tomentosa at a concentration of 60%, resulting in a mortality rate of 40.3%. However, nerolidol and eugenol showed larvicidal activity, which was highest for eugenol. Nerolidol caused a 96.5% mortality rate in the R. microplus larvae at a high concentration of 30%, and eugenol caused 100% mortality at a concentration of 0.3%. In the adult immersion test, 5% eugenol was identified as a good biomolecule for controlling R. microplus, as demonstrated by its high acaricidal activity and inhibition of oviposition. PMID- 24221890 TI - Development of an indirect immunofluorescence technique for the diagnosis of toxoplasmosis in bottlenose dolphins. AB - The diagnosis of toxoplasmosis is often complicated by the lack of specific clinical symptoms or postmortem features, in humans and other animals. The only diagnostic test described so far for the serological diagnosis of Toxoplasma gondii in marine mammals is the modified agglutination test (Dubey et al., Am J Vet Res 48(8):1239-1243, 1987). The development of more sensible and specific immunological techniques requires specific antibodies, which are currently unavailable in the scientific market. Indirect immunofluorescence (IIF) is one of the most widely used methods for the diagnosis of toxoplasmosis in humans (Auer et al., Parasitol Res 12:965-970, 2000). In order to develop and apply this technique to the bottlenose dolphin (Tursiops truncatus), immunoglobulins were firstly purified using ion-exchange chromatography. The purified immunoglobulins were then injected in New Zealand rabbits in order to obtain polyclonal antibodies. These antisera were validated by the IIF technique, using as controls serum samples of dolphins infected by Toxoplasma. The results were visualized using antirabbit IgG labeled with fluorescein. This newly developed and specific serological assay was then tested with the dolphin collection of Loro Parque, Tenerife, Spain (group I), and L'Oceanografic of Valencia, Spain (group II). The obtained results in this study showed that none of the dolphins from group 1 were infected by T. gondii and two animals were positive in group 2. Furthermore, we conclude that this study has produced antibodies with high specificity against dolphin immunoglobulins and an IIF method which may be used as immunological diagnostic tools, especially for the serological diagnosis of toxoplasmosis. PMID- 24221891 TI - Patterns of interaction between Neotropical freshwater fishes and their gill Monogenoidea (Platyhelminthes). AB - Using network analysis, we looked for broad patterns of distribution of Monogenoidea gill parasites on Neotropical freshwater fishes within a host phylogenetic framework. We analyzed a database of Monogenoidea parasitizing fishes from Neotropical rivers, from 23 watersheds, based on species descriptions published until 2011. Host-parasite interactions were organized into five matrices grouping species at different taxonomic levels. The network of interactions between host families and parasite genera was significantly modular and revealed that each fish order has a unique composition of parasite genera. Hence, interactions between lower taxa were analyzed separately for the largest fish orders (Perciformes, Siluriformes, and Characiformes). Networks tended to be loosely connected and organized in modules. Despite the putative high host specificity of monogenoids, some have a wider host range that includes distantly related host species. Among the hosts, the clade composed by the piranhas (Serrasalmus spp. and related species, Serrasalmidae) stands out in terms of parasite richness per host species, resulting in a more connected network. The history of the lineages of each host order within Neotropical freshwaters seems to have a great influence on the extent of parasite sharing. The observed modularity was influenced by both spatial structure and phylogenetic relatedness of species. In average, 37 % of modules of networks between host species and parasite genera were associated with a particular river basin and 63 % of modules were associated with a host family. Hence, spatial structure determines the co occurrence of host and parasite species, but their evolutionary history is the main factor defining which interactions are possible. PMID- 24221892 TI - Hepatic 5'-monodeiodinase activity in teleosts in vitro: A survey of thirty-three species. AB - The in vitro hepatic 5'-monodeiodination of thyroxine (T4) to triiodothyronine (T3) in Oreochromis mossambicus, Channa striata, Clarias batrachus, Cyprinus carpio and Oxyeleotris marmorata was found to be time, pH and temperature dependent, and related to the amount of substrate (T4) and homogenate introduced into the reaction vessel, in a manner which was consistent with Menton-Michaelis kinetics, and thus indicative of an enzyme-regulated process. Dithiothreitol introduced into the reaction vessel stimulated T3 production in a dose-related manner.Hepatic 5'-monodeiodinase activity was also detected in a further 28 species of teleosts suggesting that the peripheral monodeiodination of T4, which is well-documented in salmonids, is also widespread amongst other teleost fishes. All species examined exhibited evidence of enzymatic deiodination, but there were marked differences in Km and Vmax values between the species. There was no apparent phylogenetic or environmental relationships to explain the widely divergent Km and/or Vmax values, nor was there a correlation between Km and Vmax when the species were considered together. PMID- 24221893 TI - Oxidation of glutathione during hydroperoxide metabolism in isolated hepatocytes of rainbow trout (Salmo gairdneri). AB - Freshly isolated rainbow trout hepatocytes were exposed to tert-butyl hydroperoxide (BuOOH), a substrate for glutathione peroxidase. BuOOH at a concentration approximately equimolar (1 mM) with intracellular reduced glutathione (GSH) caused a reversible increase in intracellular glutathione disulphide (GSSG) but did not compromise cell viability or damage membrane lipids. BuOOH at 10 mM caused a large irreversible increase in intracellular GSSG followed by efflux into the medium. Considerable leakage of lactate dehydrogenase and loss of highly unsaturated fatty acids, particularly docosahexaenoic acid also occurred. Dependence of hydroperoxide removal on flux through the hexose monophosphate pathway was suggested by the increased release of (14)CO2 from [1 (14)C] glucose from hepatocytes incubated with BuOOH. PMID- 24221894 TI - Volume regulation in glutathione-treated brook trout (Salvelinus fontinalis) erythrocytes. AB - Brook trout erythrocytes that were washed with and suspended in Ringer's solution with reduced glutathione (1.0 mM) maintained steady state cell volume for up to 24h, while those without the thiol-protective agent steadily shrank. Changes in cell volume (measured as packed cell volume, PCV) were evoked by acidic media (Ringer's at pH 6.8), hypoosmotic solutions (or both) and intracellular K(+) and Cl(-) concentrations were monitored over 4h. Acid-swollen cells failed to volume regulate or release K(+) but had significantly elevated intracellular Cl(-) Osmotically-swollen cells at pH 7.8 but not at pH 6.8 underwent regulatory volume decrease (RVD) and returned to initial levels in 2h, accompanied by release of K(+) and Cl(-) In contrast, osmotically-shrunken cells did not show regulatory volume increase. The regulatory volume decrease and concomitant K(+) release were dependent on Cl(-) implying a direct or indirect coupling of K(+) to Cl(-) transport in volume regulation. RVD was partially blocked by 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 0.1 mM), an anion exchange blocker, but was unaffected by amiloride (1.0 mM) which blocks Na(+)/H(+) exchange. Amiloride and DIDS prevented the swelling response to low pH but had no effect on control cells, suggesting involvement of Na(+)/H(+) and Cl(-)/HCO3 (-) exchanges in acid-induced cell swelling. Quinine (1.0 mM) a known blocker of K(+) channels, exacerbated the osmotically-induced swelling but had little effect on the subsequent RVD and release of KCl. The results suggest that low extracellular pH inhibits neutral C(-)-dependent K(+) release and the resultant regulatory volume decrease in osmotically-swollen cells. PMID- 24221895 TI - Measurement of plasma leucine flux in rainbow trout (Salmo gairneri R.) using osmotic pump. Preliminary investigations on influence of diet. AB - A method for the direct measurement of plasma amino acid flux, in rainbow trout, using the continuous infusion of L-[U-(14)C]-leucine with ALZET mini-osmotic pumps implanted into the peritoneal cavity, was developed. The fish were fed successively on three different diets (a commercial control diet, a semi-purified diet and a purified diet) during the 4 weeks of experiment. The amounts of radioactivity in the free pool and the protein of both the plasma and skin mucus were measured in these fish. The total flux of leucine was calculated either from the specific activity of leucine in the plasma (61.8 mg leucine. 100 g(-1).d(-1)) or from the amounts of labelled and unlabelled leucine flowing into the skin mucus protein (61.5 mg leucine. 100g(-1).day(-1)). The total plasma flux was not affected by changes in the diet. The contributions of total leucine oxidation and whole body protein turnover to plasma leucine flux (80% and 20% respectively) were estimated in fish fed the semi-purified diet. PMID- 24221896 TI - Cortisol treatment improves the development of hypoosmoregulatory mechanisms in the euryhaline rainbow trout, Salmo gairdneri. AB - The effect of cortisol on osmoregulatory parameters was studied in rainbow trout, (Salmo gairdneri), kept in freshwater (FW) and/or transferred to seawater (SW). Repeated injections of 20 ug cortisol/g fish stimulated gill and gut Na(+)/K(+) ATPase activity and reduced plasma Na(+) and Cl(-) levels after 2 weeks of treatment in FW-adapted fish. Cortisol doses of 0.05 and 1.0 ug/g were without effect. Repeated injections of 10 ug cortisol/g stimulated gill Na(+)/K(+)-ATPase activity and reduced plasma Na+ and Cl(-) levels in fish in FW, and significantly improved ion regulation after their transfer to 28SW. Higher doses of cortisol (10 and 20 ug/g) induced hyperglycemia, whereas low doses (0.05 and 1.0 ug/g were without effect or induced hypoglycemia. Plasma glucose levels decreased in cortisol-treated fish transferred to SW, whereas transient hyperglycemia was seen in the control fish. PMID- 24221897 TI - Absence of binding and impermeability to ferritins of gill endothelium in marine teleosts. AB - The surface binding characteristics and permeability properties of the endothelium of secondary lamellae from the gills of several species of marine teleosts were investigated by introducing cationized ferritin and native ferritin into the microcirculation under normal environmental conditions. Neither type of ferritin bound to the luminal surface of the gill endothelium. No transcellular movement of cationized ferritin was detected, either via transendothelial channels or individual vesicles, nor was passage of cationized ferritin through the tight intercellular junctions of the endothelium observed. Anionic binding sites in the endothelial basement membranes could not be identified. Binding and transport of ferritin were unaffected by normal changes in environmental temperatures over the range of -2 to + 15 degrees C. These findings suggest that the endothelial cell surface of the gills from these fishes is a primary barrier to the extracapillary movement of blood borne constituents. PMID- 24221898 TI - A respirometer with controlled water quality and computerized data acquisition for experiments with swimming fish. AB - This paper describes the design of a modified Brett-type respirometer for use with fish up to 2 kg at swimming speeds as high as 2.5 m.s(-1). Control of the respirometer, experimental monitoring and data acquisition are performed by computer. Water velocity, temperature, pH, dissolved oxygen and carbon dioxide can be controlled at predetermined levels to enable experiments to be conducted over several days with minimal deterioration in water quality. PMID- 24221900 TI - Effects of paraquat treatment on fish transaminase molecular subforms. AB - The effects of paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride) treatment were investigated in carp, silver carp and wels. The serum glutamic oxalacetic transaminase (GOT; L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1.) level was enhanced by 50% at 1 ppm exposure and by 100% at 10 ppm exposure in all species, and there was a change in the distribution of the molecular subforms of GOT in the liver and heart. The activities of the individual subforms decreased with increasing PQ concentration or after a longer exposure. In some cases, one of the subforms was no longer present in the liver. An increased serum GOT activity, a decreased enzyme activity in different organs and the disappearance of molecular subform indicate tissue damage. PMID- 24221899 TI - Oxygen uptake in the Antarctic teleost Pagothenia borchgrevinki. Limitations imposed by X-cell gill disease. AB - Fish in a population of Pagothenia borchgrevinki in McMurdo Sound, Antarctica, are affected by a gill disease (X-cell disease) which causes tissue hyperplasia that results in a decreased gill surface area and an increased water/blood diffusion distance. P. borchgrevinki acquires 95% of its oxygen via the gills, but damage to the gills by X-cell disease did not affect this function. There was no compensatory shift to cutaneous respiration. X-cell disease reduced the ability for oxygen uptake at low ambient PO 2 and the decreased uptake was related to the extent of the disease. O 2 max was greatly reduced in X-cell affected fish and substantially reduced their aerobic potential. This effect may impair the ability of diseased fish to catch prey and avoid predators. PMID- 24221901 TI - Effects of hypoxia on blood pressure and heart rate in three marine teleosts. AB - Ventral aortic blood pressure (Pva) and heart rate (HR) responses to rapidly (within 1 min) induced hypoxia (PWO2=4-5.3 kPa) were investigated in vivo in three species of marine teleosts (shorthorn sculpin, Myoxo-cephalus scorpius; eel pout, Zoarces viviparus; and five-bearded rockling, Ciliata mustela). Fish were exposed to hypoxia for 4 min (M.scorpius) or 5 min (Z.viviparus and C.mustela).Pva was unaffected in M.scorpius, decreased in Z.viviparus and increased in C.mustela in response to hypoxia.Untreated M.scorpius and Z. viviparus responded with a characteristic bradycardia during hypoxia, whereas C.mustela developed no bradycardia. Injection of atropine followed by the beta adrenoceptor antagonist sotalol in M.scorpius and Z. viviparus, revealed that both the inhibitory (cholinergic) and the excitatory (adrenergic) influence on the heart increase during hypoxia. The inhibitory influence dominates, resulting in the observed bradycardia. PMID- 24221902 TI - Simultaneous specific in planta visualization of root-colonizing fungi using fluorescence in situ hybridization (FISH). AB - In planta detection of mutualistic, endophytic, and pathogenic fungi commonly colonizing roots and other plant organs is not a routine task. We aimed to use fluorescence in situ hybridization (FISH) for simultaneous specific detection of different fungi colonizing the same tissue. We have adapted ribosomal RNA (rRNA) FISH for visualization of common mycorrhizal (arbuscular- and ectomycorrhiza) and endophytic fungi within roots of different plant species. Beside general probes, we designed and used specific ones hybridizing to the large subunit of rRNA with fluorescent dyes chosen to avoid or reduce the interference with the autofluorescence of plant tissues. We report here an optimized efficient protocol of rRNA FISH and the use of both epifluorescence and confocal laser scanning microscopy for simultaneous specific differential detection of those fungi colonizing the same root. The method could be applied for the characterization of other plant-fungal interactions, too. In planta FISH with specific probes labeled with appropriate fluorescent dyes could be used not only in basic research but to detect plant colonizing pathogenic fungi in their latent life-period. PMID- 24221903 TI - Comparison of root-associated communities of native and non-native ectomycorrhizal hosts in an urban landscape. AB - Non-native tree species are often used as ornamentals in urban landscapes. However, their root-associated fungal communities remain yet to be examined in detail. Here, we compared richness, diversity and community composition of ectomycorrhizosphere fungi in general and ectomycorrhizal (EcM) fungi in particular between a non-native Pinus nigra and a native Quercus macrocarpa across a growing season in urban parks using 454-pyrosequencing. Our data show that, while the ectomycorrhizosphere community richness and diversity did not differ between the two host, the EcM communities associated with the native host were often more species rich and included more exclusive members than those of the non-native hosts. In contrast, the ectomycorrhizosphere communities of the two hosts were compositionally clearly distinct in nonmetric multidimensional ordination analyses, whereas the EcM communities were only marginally so. Taken together, our data suggest EcM communities with broad host compatibilities and with a limited numbers of taxa with preference to the non-native host. Furthermore, many common fungi in the non-native Pinus were not EcM taxa, suggesting that the fungal communities of the non-native host may be enriched in non-mycorrhizal fungi at the cost of the EcM taxa. Finally, while our colonization estimates did not suggest a shortage in EcM inoculum for either host in urban parks, the differences in the fungi associated with the two hosts emphasize the importance of using native hosts in urban environments as a tool to conserve endemic fungal diversity and richness in man-made systems. PMID- 24221904 TI - Relationship between endothelial vasomotor function and strut coverage after implantation of drug-eluting stent assessed by optical coherence tomography. AB - The use of drug-eluting stent (DES) has been associated with incomplete endothelialization and coronary endothelial dysfunction. However, the relationship between endothelial vasomotor function and strut coverage evaluated by optical coherence tomography (OCT) has not been sufficiently assessed. Therefore, we evaluated the relationship between endothelial vasomotor function and the degree of stent strut coverage after DES implantation. Coronary angiography and OCT were performed in 112 patients at the 6-month follow-up after DES implantation. The patients were divided into tertiles according to the degree of strut coverage as was assessed by OCT. Endothelial vasomotor function was evaluated with intracoronary infusion of incremental doses of acetylcholine (Ach; 10(-8)-10(-6) mol/L). Vascular responses at the proximal and distal segments to the stent margin were evaluated by quantitative coronary angiography analysis before and after Ach infusion. The percentage of uncovered struts in tertiles 1-3 was 4.2 +/- 3.3, 17.3 +/- 4.2 and 44.5 +/- 14.4 %, respectively, (p < 0.001). The percentage of maximal vasoconstriction in tertiles 1-3 was 8.3, 9.1 and 8.1 % at proximal segment to the stent margin (p = 0.95), respectively, and 13.9, 11.1 and 14.2 % at distal segment to the stent margin (p = 0.74), respectively. The percentage of uncovered struts was not correlated with the degree of vasomotor function (r = -0.01, p = 0.92 at the proximal segment; r = -0.07, p = 0.47 at the distal segment). The percentage of strut coverage was not associated with the degree of abnormal vasoconstriction in response to intracoronary infusion of Ach 6 months after DES implantation. PMID- 24221905 TI - In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI. AB - To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 +/- 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 +/- 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 +/- 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 +/- 61 ms, and average T1 of the left-ventricular (LV) was 956 +/- 25 ms (p < 0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV. PMID- 24221906 TI - Single-beat real-time three-dimensional echocardiographic automated contour detection for quantification of left ventricular volumes and systolic function. AB - To assess the feasibility and accuracy in measuring left ventricular (LV) end diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) with Siemens single-beat real-time 3D transthoracic echocardiography. The LV volumes and EF were measured in 3D datasets acquired by six imaging modes (time-1 harmonic (T1H), time-1-fundamental, time-2-harmonic, time-2-fundamental, space-1 harmonic (S1H), and space-1-fundamental) in 41 patients using the automated contouring algorithm and compared with manually corrected 3DE QLAB measurements. The main determinates of the temporal and spatial resolutions of 3D datasets acquired were the fundamental and harmonic modes. Consequently, the S1H mode had the lowest volume rate and highest spatial resolution. Compared with the 3DE QLAB analysis, the S1H mode resulted in the best LV volumes and EF estimates in all patients (0 +/- 10 % for EF, -7 +/- 44 ml for EDV, -7 +/- 39 ml for ESV) and in the 10 patients with correct LV contour tracking according to a visual assessment from the multiplanar reconstruction views in all six modes (0 +/- 9 % for EF, -3 +/- 23 ml for EDV, -2 +/- 14 ml for ESV). The T1H mode was the best alternative. Overall 28 patients (68 %) could be analysed automatically and satisfyingly with the S1H and T1H modes: 0 +/- 8 % (EF), 0 +/- 27 ml (EDV) and -1 +/- 16 ml (ESV). The accuracy of the Siemens automated RT-3D algorithm in measuring LV volumes and EF is significantly influenced by the different imaging modes. The S1H mode may be the preferred 3D acquisition mode, supplemented by the T1H mode in enlarged LVs that do not fit in the S1H acquisition sector. PMID- 24221907 TI - Nanopatterning palladium surface layers through electrochemical deposition and dissolution of zinc in ionic liquid. AB - Cracklike nanopatterned palladium surface layers have been produced by a green chemistry method based on in situ electrochemical deposition-dissolution of zinc (Zn-ECDD) in an ionic liquid bath. During the cathodic process, reactive Zn was electrochemically deposited onto a polycrystalline Pd substrate. During the subsequent anodic process, Zn was removed from the substrate through electrochemical dissolution. Scanning electron microscope (SEM) measurements showed that repetitive Zn-ECDD mediated by potential cycles results in the nanopatterning of Pd surface layers, characterized by uniform crack appearance with well-distributed concave spacings separated by nanowidth cracks. Energy dispersive X-ray microscopy (EDX) studies revealed that the nanopatterned surface layers chemically contain a small amount of Zn. A mechanism based on the development of stress induced by the Zn-ECDD on Pd surfaces was proposed to be responsible for the nanopatterning of Pd surface layers. Electrochemical oxidation of formic acid and reduction of nitrite were studied as model reactions to demonstrate potential applications of the nanopatterned Pd electrode to electrocatalysis and electrochemical determination of environmental contaminants. Highly improved electrochemical responses were obtained on the nanopatterned Pd for the two reactions, compared to the untreated Pd. PMID- 24221908 TI - Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death. AB - STUDY QUESTION: Can Sphingosine-1-phosphate (S1P), a ceramide-induced death pathway inhibitor, prevent cyclophosphamide (Cy) or doxorubicin (Doxo) induced apoptotic follicle death in human ovarian xenografts? SUMMARY ANSWER: S1P can block human apoptotic follicle death induced by both drugs, which have differing mechanisms of cytotoxicity. WHAT IS KNOWN ALREADY: S1P has been shown to decrease the impact of chemotherapy and radiation on germinal vesicle oocytes in animal studies but no human translational data exist. STUDY DESIGN, SIZE, DURATION: Experimental human ovarian xenografting to test the in vivo protective effect of S1P on primordial follicle survival in the chemotherapy setting. The data were validated by assessing the same protective effect in the ovaries of xenografted mice in parallel. PARTICIPANTS/MATERIALS, SETTING, METHODS: Xenografted mice were treated with Cy (75 mg/kg), Cy+S1P (200 MUM), Doxo (10 mg/kg), Doxo+S1P or vehicle only (Control). S1P was administered via continuous infusion using a mini osmotic pump beginning 24 h prior to and ending 72 h post-chemotherapy. Grafts were then recovered and stained with anti-caspase 3 antibody for the detection of apoptosis in primordial follicles. The percentage of apoptotic to total primordial follicles was calculated in each group. MAIN RESULTS AND THE ROLE OF CHANCE: Both Cy and Doxo resulted in a significant increase in apoptotic follicle death in human ovarian xenografts compared with controls (62.0 +/- 3.9% versus 25.7 +/- 7.4%, P < 0.01 and 76.7 +/- 7.4% versus 25.7 +/- 7.4%, P < 0.01, respectively). This chemotherapy-induced apoptotic death was reduced both in the Cy+S1P (32.7 +/- 4.4%, P < 0.01) and the Doxo+S1P group (27.1 +/- 7.6%, P < 0.01) compared with Cy and Doxo groups, respectively. In the Doxo+S1P and Cy+S1P groups, the percentages of apoptotic follicles were similar to those of vehicle treated controls (P > 0.05). The findings from the ovaries of the severe combined immunodeficient mice mirrored the findings with human tissue. LIMITATIONS, REASONS FOR CAUTION: The functionality of the rescued human ovarian follicles needs to be evaluated in future studies though the studies in rodents showed that rescued oocytes can result in healthy offspring. In addition, the impact of S1P on cancer cells should be further studied. WIDER IMPLICATIONS OF THE FINDINGS: S1P and its future analogs hold promise for preserving fertility by pharmacological means for patients undergoing chemotherapy. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by NIH's NICHD and NCI (5R01HD053112-06 and 5R21HD061259-02) and the Flemish Foundation for Scientific Research (FWO-Vlaanderen, grant number FWO G0.065.11N10). The authors have no conflicts of interest to disclose. PMID- 24221910 TI - Fertility preservation after caesarean delivery in a woman diagnosed with Morbus Hodgkin disease during pregnancy. PMID- 24221911 TI - Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta analysis. AB - BACKGROUND: Recently, a relationship between recurrent pregnancy loss (RPL) and Apolipoprotein E (Apo E) gene polymorphisms has been proposed. In order to investigate the real association between Apo E polymorphisms and RPL, our meta analysis was carried out. METHODS: We estimated the association with RPL risk under dominant and recessive models, in combination with the OR and RR with a 95% confidence interval (CI), which was used to assess the association between RPL and Apo E polymorphisms. RESULTS: According to our criterion, there were 6 studies included. The dominant model used the E4/E3 group and the OR was 1.919 (95 %CI: 1.016-3.625, I(2) = 53.8%), the RR was 1.308 (95%Cl: 1.071-1.598) suggesting that carriers of the E4 allele would have a higher risk of causing spontaneous miscarriages. In addition, the OR was 0.727 (95%CI: 0.566-0.932, I(2) = 0.0%) and RR was 0.923 (95%CI: 0.867-0.982) in a fixed model for E3/E3 homozygotes versus other genotypes, suggesting that the Apo E3 polymorphism could be a protective factor. The OR was 1.365 (95% CI: 1.029-1.811, I(2) = 0 .0%) in a fixed model comparing the E2 allele with the E3 allele, suggesting that Apo E2 polymorphisms may contribute to RPL as a risk factor. Furthermore, after conducting sensitivity analysis in the E4/E3 group, the results showed this to be consistent and the OR was 2.249 (95%CI: 1.474-3.431). CONCLUSIONS: There is a close association between RPL and Apo E gene polymorphisms. For RPL, the Apo E4 polymorphism could be a risk factor, the Apo E3 polymorphism may be a protective factor and the Apo E2 polymorphism may be another potential risk factor. PMID- 24221909 TI - Long-term treatment of hydrogen-rich saline abates testicular oxidative stress induced by nicotine in mice. AB - PURPOSE: The present study was designed to test the hypothesis that long-term treatment with hydrogen-rich saline abated testicular oxidative stress induced by nicotine in mice. METHODS: The effects of hydrogen-rich saline (6 ml/kg, i.p.), vitamin C (60 mg/kg, i.p.) and vitamin E (100 mg/kg, i.p.) on reproductive system and testicular oxidative levels in nicotine-treated (4.5 mg/kg, s.b.) mice were investigated. RESULTS: It was found that vitamin C and vitamin E attenuated serum oxidative level, but did not lower testicular oxidative levels in mice subjected to chronic nicotine treatment, and did not improve the male reproductive damage and apoptosis induced by nicotine. Different from normal antioxidants, vitamin C and vitamin E, hydrogen-rich saline abated oxidative stress in testis, and protected against nicotine-induced male reproductive damages. CONCLUSION: Our results first demonstrated that long-term treatment with hydrogen-rich saline attenuated testicular oxidative level and improved male reproductive function in nicotine-treated mice. PMID- 24221912 TI - Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles. AB - PURPOSE: The aim of our study was to determine whether there are any differences in the cumulus cell gene expression profile of mature oocytes derived from modified natural IVF and controlled ovarian hyperstimulation cycles and if these changes could help us understand why modified natural IVF has lower success rates. METHODS: Cumulus cells surrounding mature oocytes that developed to morulae or blastocysts on day 5 after oocyte retrieval were submitted to microarray analysis. The obtained data were then validated using quantitative real-time PCR. RESULTS: There were 66 differentially expressed genes between cumulus cells of modified natural IVF and controlled ovarian hyperstimulation cycles. Gene ontology analysis revealed the oxidation-reduction process, glutathione metabolic process, xenobiotic metabolic process and gene expression were significantly enriched biological processes in MNIVF cycles. Among differentially expressed genes we observed a large group of small nucleolar RNA's whose role in folliculogenesis has not yet been established. CONCLUSION: The increased expression of genes involved in the oxidation-reduction process probably points to hypoxic conditions in modified natural IVF cycles. This finding opens up new perspectives for the establishment of the potential role that oxidation-reduction processes have in determining success rates of modified natural IVF. PMID- 24221913 TI - Heterogeneous distribution of histone methylation in mature human sperm. AB - PURPOSE: To analyze the presence of various histone modifications in ejaculated human spermatozoa METHODS: In this prospective study, seminal ejaculates from 39 normozoospermic individuals were evaluated for semen analysis and the presence of histone modifications in isolated nuclei. RESULTS: We observed heterogeneous presence of histone methylation in normal mature human sperm. We observed that 12 to 30 % of the nuclei of normal sperm contain a heterogeneous distribution of the marks H3K4Me1, H3K9Me2, H3K4Me3, H3K79Me2, and H3K36Me3. Moreover, the presence of these marks is higher in the poor motile fraction of the ejaculate, which is associated with poor morphology and functional quality. In contrast, we did not observe histone acetylation (H3K4Ac and H4K5Ac) in normal or abnormal mature human sperm CONCLUSIONS: Defects in the process of spermatogenesis may alter the correct epigenetic programming in mature sperm. Further studies are required to evaluate the impact of these findings in human infertility. PMID- 24221915 TI - Meta-analysis on brain representation of experimental dental pain. AB - Functional magnetic resonance imaging (fMRI) has been widely used for investigating the brain representation associated with dental pain evoked by pulpal electrical stimulation. However, because of the heterogeneity of experimental designs and the small sample size of individual studies, the common brain representation regarding dental pain has remained elusive. We used imaging meta-analysis to investigate six dental pain-related fMRI studies (n = 87) and tested 3 hypotheses: (1) Dental pain is associated with the 'core' pain-related network; (2) pain-related brain activation is somatotopically organized in the somatosensory cortex; and (3) dental pain is associated with the cognitive affective network related to pain. Qualitative and quantitative meta-analyses revealed: (1) common activation of the core pain-related network, including the somatosensory cortex, the insula, and the cingulate cortex; (2) inconsistency in somatotopically organized activation of the primary somatosensory cortex; and (3) common activation in the dorsolateral prefrontal cortex, suggesting a role of re appraisal and coping in the experience of dental pain. In conclusion, fMRI combined with pulpal stimulation can effectively evoke activity in the pain related network. The dental pain-related brain representation disclosed the mechanisms of how sensory and cognitive-affective factors shape dental pain, which will help in the development of more effective customized methods for central pain control. PMID- 24221916 TI - Free Web-based personal health records: an analysis of functionality. AB - This paper analyzes and assesses the functionality of free Web-based PHRs as regards health information, user actions and connection with other tools. A systematic literature review in Medline, ACM Digital Library, IEEE Digital Library and ScienceDirect was used to select 19 free Web-based PHRs from the 47 PHRs identified. The results show that none of the PHRs selected met 100% of the 28 functions presented in this paper. Two free Web-based PHRs target a particular public. Around 90 % of the PHRs identified allow users throughout the world to create their own profiles without any geographical restrictions. Only half of the PHRs selected provide physicians with user actions. Few PHRs can connect with other tools. There was considerable variability in the types of data included in free Web-based PHRs. Functionality may have implications for PHR use and adoption, particularly as regards patients with chronic illnesses or disabilities. Support for standard medical document formats and protocols are required to enable data to be exchanged with other stakeholders in the health care domain. The results of our study may assist users in selecting the PHR that best fits their needs, since no significant connection exists between the number of functions of the PHRs identified and their popularity. PMID- 24221917 TI - X-Ray assessment of the effect of pedicle screw on vertebra and spinal canal growth in children before the age of 7 years. AB - PURPOSE: To determine the reliability of pedicle screws placed in children younger than 7 years of age, and to evaluate the effect of pedicle screw insertion on further growth of the vertebra and spinal canal. METHODS: A retrospective study of 35 consecutive patients through Jan 2003-Dec 2010 for congenital scoliosis in <7 years children was performed at one spine center. Patients undergoing pedicle screw instrumentation of at least two levels, which had been followed-up for at least 24 months were included. Measurements were performed in instrumented and adjacent non-instrumented levels. The effect of pedicle screw insertion on further growth was evaluated. RESULTS: The average age at surgery was 4.4 year (53 months, range, 23-84 months). 190 segments in 35 patients met the inclusion criteria. 77 segments had no screws and 113 had at least one screw. There was a significant difference between the pre-operative and final follow-up values of the measurement of spinal canal and vertebral body parameters (P < 0.001). No significant difference existed between growth rates of vertebral bodies and the sagittal diameters of spinal canal with or without screws. The growth rates of vertebral bodies in lumbar spine were higher than in thoracic spine in both instrumented and adjacent groups. CONCLUSION: Pedicle screw instrumentation does not cause a retardation effect on the development of vertebral bodies and the spinal canal in children at an early age. It is a safe and reliable procedure to achieve a stable fixation. PMID- 24221918 TI - Inflammatory pain pattern and pain with lumbar extension associated with Modic 1 changes on MRI: a prospective case-control study of 120 patients. AB - PURPOSE: To compare, in a case-control study, clinical characteristics of patients with low back pain (LBP) with and without Modic 1 signal changes on MRI. METHODS: Patients with chronic non-specific LBP and a recent (<6 months) MRI were prospectively screened and included in Modic 1 group or control group. Patients in control group were age- and gender-matched with patients with Modic 1 group. Pain characteristics, including night pain and worse pain on waking and morning stiffness, were recorded. The presence of at least one of these three characteristics indicated an inflammatory pain pattern. Patients were evaluated by questionnaires and physical examination (including lumbar range of motion). Data were analyzed by univariate and multivariate analyses. RESULTS: 120 patients were included (60 in each group). The groups did not differ in sedentary work (p = 0.25), morning stiffness for >60 min (p = 0.19), waking at night (p = 0.08), worse pain on waking (p = 0.09), back stiffness (p = 0.12), or pain with flexion (p = 0.87). Modic 1 patients more frequently exhibited an inflammatory pain pattern (p = 0.006), worse pain with lumbar extension (p < 0.005) and responded better to oral steroids (p = 0.004) than did controls. On multivariate analysis, Modic 1 changes were associated with sedentary work [odds ratio 0.22 (95% confidence interval 0.05-0.93)], pain with lumbar extension [11.2 (3.1-40.4)] and an inflammatory pain pattern [4.5 (1.2-16.9)]. CONCLUSIONS: Characteristics of patients with LBP and Modic 1 changes on MRI consist of an inflammatory pain pattern and pain with lumbar extension. Level of evidence 3b. PMID- 24221920 TI - Long-term follow-up of clinical and radiological outcome after cervical laminectomy. AB - PURPOSE: To evaluate long-term clinical and radiological results of cervical laminectomy without adjuvant-instrumented fusion for degenerative spinal cord compression. METHODS: A retrospective follow-up study of patients in which clinical data (n = 207), questionnaires (n = 96) and fluoroscopy (n = 77) were reviewed. RESULTS: Postoperative perceived recovery was reported by 76 and 63 % of patients at 3 months and 9 years, respectively. Functional status remained unchanged. The incidence of kyphosis and segmental instability was 15 and 18 %, respectively, and occurred almost exclusively if preoperative lordosis was <20 degrees . Neither kyphosis nor segmental instability correlated to perceived recovery and no predisposing variables were identified. CONCLUSIONS: Cervical laminectomy without adjuvant-instrumented fusion should be considered as a treatment for compressive degenerative cervical myelopathy in patients with a lordotic cervical spine without congenital deformities. Additional reconstructive correction of the cervical spine is only proven appropriate in selected cases. PMID- 24221919 TI - Primary prevention of disc degeneration-related symptoms. AB - INTRODUCTION: It has been shown previously that a history of low back pain often begins in childhood or adulthood. Indeed, the prevalence of severe back symptoms among schoolchildren is not insignificant. Possibilities for the primary prevention of intervertebral disc degeneration-related conditions are poorly reported in the literature despite the assumed socio-economical impact of the prevention of these conditions. METHODS: In this review, the authors have collated published data on the prevalence and risk factors of childhood low back pain as well as the structure and results of published primary prevention programs. RESULTS: The prevalence of self-reported low back pain is 7-65% among children and it increases with age. Several lifestyle factors have been reported as significant risk factors for back pain, many of which are related to the schools. Current educational primary prevention programs in schools show no clear or long-term stable effect. CONCLUSION: Considering the growing evidence about the importance of normal and bad posture, an exercise-based posture correction program is suggested as a school-based primary prevention of disc degeneration related symptoms. Further, prospective randomized studies with more than 20 years follow-up, however, are strongly required to confirm it. PMID- 24221921 TI - Effect of varying number of OSEM subsets on PET lesion detectability. AB - Iterative reconstruction has become the standard for routine clinical PET imaging. However, iterative reconstruction is computationally expensive, especially for time-of-flight (TOF) data. Block-iterative algorithms such as ordered-subsets expectation maximization (OSEM) are commonly used to accelerate the reconstruction. There is a tradeoff between the number of subsets and reconstructed image quality. The objective of this work was to evaluate the effect of varying the number of OSEM subsets on lesion detection for general oncologic PET imaging. METHODS: Experimental phantom data were taken from the Utah PET Lesion Detection Database, modeling whole-body oncologic (18)F-FDG PET imaging of a 92-kg patient. The experiment consisted of 24 scans over 4 d on a TOF PET/CT scanner, with up to 23 lesions (diameter, 6-16 mm) distributed throughout the thorax, abdomen, and pelvis. Images were reconstructed with maximum-likelihood expectation maximization (MLEM) and with OSEM using 2-84 subsets. The reconstructions were repeated both with and without TOF. Localization receiver-operating-characteristic (LROC) analysis was applied using the channelized nonprewhitened observer. The observer was first used to optimize the number of iterations and smoothing filter for each case that maximized lesion detection performance for these data; this was done to ensure that fair comparisons were made with each test case operating near its optimal performance. The probability of correct localization and the area under the LROC curve were then analyzed as functions of the number of subsets to characterize the effect of OSEM on lesion-detection performance. RESULTS: Compared with the baseline MLEM algorithm, lesion-detection performance with OSEM declined as the number of subsets increased. The decline was moderate out to about 12-14 subsets and then became progressively steeper as the number of subsets increased. Comparing TOF with non-TOF results, the magnitude of the performance drop was larger for TOF reconstructions. CONCLUSION: PET lesion-detection performance is degraded when OSEM is used with a large number of subsets. This loss of image quality can be controlled using a moderate number of subsets (e.g., 12-14 or fewer), retaining a large degree of acceleration while maintaining high image quality. The use of more aggressive subsetting can result in image quality degradations that offset the benefits of using TOF or longer scan times. PMID- 24221922 TI - Comparison of Bruce treadmill exercise test protocols: is ramped Bruce equal or superior to standard bruce in producing clinically valid studies for patients presenting for evaluation of cardiac ischemia or arrhythmia with body mass index equal to or greater than 30? AB - Clinically valid cardiac evaluation via treadmill stress testing requires patients to achieve specific target heart rates and to successfully complete the cardiac examination. METHODS: A comparison of the standard Bruce protocol and the ramped Bruce protocol was performed using data collected over a 1-y period from a targeted patient population with a body mass index (BMI) equal to or greater than 30 to determine which treadmill protocol provided more successful examination results. RESULTS: The functional capacity, metabolic equivalent units achieved, pressure rate product, and total time on the treadmill as measured for the obese patients were clinically valid and comparable to normal-weight and overweight patients (P < 0.001). Data gathered from each protocol demonstrated that the usage of the ramped Bruce protocol achieved more consistent results in comparison across all BMI groups in achieving 80%-85% of their age-predicted maximum heart rate. CONCLUSION: This study did not adequately establish that the ramped Bruce protocol was superior to the standard Bruce protocol for the examination of patients with a BMI equal to or greater than 30. PMID- 24221923 TI - Ultrastructure of the partially coated reticulum and dictyosomes during endocytosis by soybean protoplasts. AB - Individual and serial sections were used to obtain detailed information regarding the morphology and distribution of the partially coated reticulum (PCR) and to determine its relationship with dictyosomes in endocytotically active soybean (Glycine max. (L.) Merr.) protoplasts. The results confirm and extend the description of the PCR provided by T.C. Pesacreta and W.J. Lucas (1985, Protoplasma 125, 173-184) from whole cells of selected angiosperms. The PCR of soybean protoplasts consists of a set of interconnected tubular membranes bearing a clathrin-like coat over part of their cytoplasmic surface. A dilation, sometimes containing small vesicles, is frequently seen in this organelle. The PCR often appears associated with dictyosomes but also occurs independent of other cell organelles. Only one example of a direct connection between the PCR and dictyosomes was observed.Following adsorptive endocytosis of cationized ferritin, the label appears in the PCR within 2 min and accumulates with time. It is never observed in the membrane dilations. Serial sectioning established that dictyosomes are labelled with cationized ferritin around the periphery of several cisternae, including those on both sides of the same dictyosome. PMID- 24221924 TI - The occurrence of leghemoglobin protein in the uninfected interstitial cells of soybean root nodules. AB - The distribution of leghemoglobin (Lb) in resin-embedded root nodules of soybean (Glycine max (L.) Merr.) was investigated using immunogold labeling. Using anti Lb immunoglobulin G and protein A-gold, Lb or its apoprotein was detected both in cells infected by Bradyrhizobium japonicum and in uninfected interstitial cells. Leghemoglobin was present in the cytoplasm, exclusive of the organelles, and in the nuclei of both cell types. In a comparison of the density of labeling in adjacent pairs of infected and uninfected cells, Lb was found to be about four times more concentrated in infected cells. This is the first report of Lb in uninfected cells of any legume nodule; it raises the possibility that this important nodule-specific protein may participate in mediating oxygen flow to host plant organelles throughout the infected region of the nodule. PMID- 24221925 TI - Glycine decarboxylase is confined to the bundle-sheath cells of leaves of C3-C 4 intermediate species. AB - Immunogold labelling has been used to determine the cellular distribution of glycine decarboxylase in leaves of C3, C3-C4 intermediate and C4 species in the genera Moricandia, Panicum, Flaveria and Mollugo. In the C3 species Moricandia foleyi and Panicum laxum, glycine decarboxylase was present in the mitochondria of both mesophyll and bundle-sheath cells. However, in all the C3-C4 intermediate (M. arvensis var. garamatum, M. nitens, M. sinaica, M. spinosa, M. suffruticosa, P. milioides, Flaveria floridana, F. linearis, Mollugo verticillata) and C4 (P. prionitis, F. trinervia) species studied glycine decarboxylase was present in the mitochondria of only the bundle-sheath cells. The bundle-sheath cells of all the C3-C4 intermediate species have on their centripetal faces numerous mitochondria which are larger in profile area than those in mesophyll cells and are in close association with chloroplasts and peroxisomes. Confinement of glycine decarboxylase to the bundle-sheath cells is likely to improve the potential for recapture of photorespired CO2 via the Calvin cycle and could account for the low rate of photorespiration in all C3-C4 intermediate species. PMID- 24221926 TI - Inorganic-carbon uptake by a small-celled strain of Stichococcus bacillaris. AB - Air-grown cells of a marine, small-celled (2 MUm diameter) strain of Stichococcus bacillaris contained appreciable carbonic-anhydrase activity but this was repressed when cells were grown on air enriched with 5% (v/v) CO2. Assay of carbonic-anhydrase activity using intact cells and cell extracts showed all activity was intracellular in this Stichococcus strain. Measurement of inorganic carbon-dependent photosynthetic O2 evolution at pH 5.0, where CO2 is the predominant form of inorganic carbon, showed that the concentration of inorganic carbon required for half-maximal rate of photosynthetic O2 evolution [K0.5(CO2)] was 4.0 MUM for both air- and CO2-grown cells. At pH 8.3 the K0.5(CO2) was 0.3 mM for air-grown and 0.6 mM for CO2-grown cells. Sodium ions did not enhance bicarbonate utilization. Measurement of the internal inorganic-carbon pool (HCO 3 (-) +CO2) by the silicone-oil-layer centrifugal filtering technique showed that air- and CO2-grown cells were able to concentrate inorganic carbon up to 20-fold in relation to the external medium at pH 5.0 but not at pH 8.3. In this alga the high affinity for CO2 and inorganic-carbon accumulation in CO2- and air-grown cells results from active CO2 transport that is not dependent on carbonic anhydrase activity. PMID- 24221927 TI - Separation and purification of the tonoplast ATPase and pyrophosphatase from plants with constitutive and inducible Crassulacean acid metabolism. AB - Tonoplast vesicles were isolated from Kalanchoe daigremontiana Hamet et Pierrer de la Bathie and Mesembryanthemum crystallinum L., exhibiting constitutive and inducible crassulacean acid metabolism (CAM), respectively. Membrane-bound proteins were detergent-solubilized with 2% of Triton X-100. During CAM induction in M. crystallinum, ATPase activity increases four-fold, whereas pyrophosphatase activity decreases somewhat. With all plants, ATPase and pyrophosphatase could be separated by size-exclusion chromatography (SEC, Sephacryl S 400), and the ATPase was further purified by diethylaminoethyl-ion-exchange chromatography. Sodium dodecyl-sulfate electrophoresis of the SEC fractions from K. daigremontiana containing maximum ATPase activity separates several protein bands, indicating subunits of 72, 56, 48, 42, 28, and 16 kDa. Purified ATPase from M. crystallinum in the C3 and CAM states shows a somewhat different protein pattern. With M. crystallinum, an increase in ATP-hydrolysis and changes in the subunit composition of the native enzyme indicate that the change from the C3 to the CAM state is accompanied by de-novo synthesis and by structural changes of the tonoplast ATPase. PMID- 24221928 TI - Photoprotection of phytochrome. AB - High-fluence-rate white light is shown to retard the degradation of phytochrome in etiolated seedlings of four different species: Amaranthus caudatus, Phaseolus radiatus (mung bean), Pisum sativum (garden pea), and Avena sativa (oat). In Amaranthus, a high photon fluence rate (approx. 1000 MUmol . m(-2) . s(-1)) preserved nearly 50% of the total phytochrome over a period of 5 h; at 3 MUmol . m(-2) . s(-1), less than 8% remained over the same period. Kinetics of the loss of total phytochrome could be interpreted in terms of two populations, one with rapid, and one with slow, turnover rates. A log-linear relationship between fluence rate and proportion of slowly degrading phytochrome was observed; a similar relationship between fluence rate and the amount of phytochrome remaining after a 5-h light treatment was seen. In mung bean, although two populations of differing degradation rates were not resolvable, a similar log-linear relationship between fluence rate and amount remaining after a standard light treatment was evident. Detailed kinetic analyses were not performed with peas and oats, but comparisons of low and high fluence rates demonstrated that photoprotection was similarly effective in these species. In Amaranthus, transfer from high to low fluence rate was accompanied by a rapid increase in degradation rate, indicating that the retarding effect of high-fluence-rate light is not a consequence of the disablement of the degradative machinery.Immunochemical analyses confirmed the existence of photoprotection in all four species, and allowed the extension of the observations to periods of light treatment during which substantial chlorophyll production occurred. Considerable photoprotection was observed in oat seedlings exposed to summer sunlight. These results are interpreted in terms of the accumulation under high fluence rates of photoconversion intermediates not available to the degradative machinery which is specific for the far-red-absorbing form of phytochrome. PMID- 24221929 TI - Regeneration of tepals, stamens and ovules in explants from perianth of Hyacinthus orientalis L. importance of explant age and exogenous hormones. AB - Regeneration of tepals, stamens and ovules from perianth explants of Hyacinthus orientalis L. in different developmental stages could be controlled by means of exogenous hormones. Perianth explants in a relatively early stage of development were competent for differentiation of tepals on Murashige and Skoog (MS) medium supplemented with 2 mg.1(-1) N(6)-benzylaminopurine (BAP) or zeatin and 0.1 mg.1( 1) 2,4-dichlorophenoxyacetic acid (2,4-D). Perianth explants in a later stage of development regenerated stamens and ovules, and marked difference was observed in the activity of BAP and zeatin in this regard. Zeatin stimulated more strongly stamen formation, while BAP enhanced ovule formation. Thus, stamens were formed when the explants were cultured for four months on medium with 2 mg.1(-1) BAP and 0.1 mg.1(-1) 2,4-D and then transferred to medium with 0.2 mg.1(-1) zeatin and 0.005 mg.1(-1) 1-naphthaleneacetic acid. On the other hand, differentiation of ovules occured in explants cultured for two weeks on the former medium and then transferred to medium with 0.1 mg.1(-1) BAP and 0.01 mg.1(-1) 2,4-D. Although ovule formation could also be obtained with 2 mg.1(-1) BAP alone, it was substantially enhanced by the presence of 0.1 mg.1(-1) 2,4-D in the medium in the early stages of culture. The results demonstrate the importance of both the developmental stage of the source organ from which explants are excised and of the hormone composition of the medium for the regeneration of different floral organs by perianth explants of Hyacinthus. PMID- 24221930 TI - Onset of desiccation tolerance during development of the barley embryo. AB - We have investigated events which take place in the developing barley (Hordeum vulgare L.) embryo during its acquisition of desiccation tolerance. Excised embryos are capable of precocious germination as early as 8 d after pollination (DAP). At this age, however, they are not capable of resisting a desiccation treatment which induces a loss of 96-98% of their initial water content. At 16 DAP the embryos germinate despite the drastic drying treatment. The pattern of in vivo and in-vitro proteins synthesized by the developing embryos from 12 DAP (desiccation-intolerant) and 16 DAP (desiccation-tolerant) were compared. A set of 25-30 proteins was identified which is denovo synthesized or enhanced during the developmental period leading to desiccation tolerance. Abscisic acid (ABA; 100 MUM) applied in vitro for 5 d to 12-DAP embryos induces desiccation tolerance and represses a subset of polypeptides preferentially associated with 16-DAP embryos. During in vitro culture of barley embryos ABA stimulates the appearance of a set of proteins and prevents the precocious germination allowing embryogenesis to continue in vitro. It also suppresses a set of germination related proteins which appear 4 h after the incubation of the dissected embryo on a germination medium without ABA. Almost all mRNAs remain functional for translation when isolated embryos are dried at the desiccation-intolerant and tolerant stages of embryo development. PMID- 24221931 TI - The source of gibberellins in the parthenocarpic development of ovaries on topped pea plants. AB - The role and source of gibberellins (GAs) involved in the development of parthenocarpic fruits of Pisum sativum L. has been investigated. Gibberellins applied to the leaf adjacent to an emasculated ovary induced parthenocarpic fruit development on intact plants. The application of gibberellic acid (GA3) had to be done within 1 d of anthesis to be fully effective and the response was concentration-dependent. Gibberellin A1 and GA3 worked equally well and GA20 was less efficient. [(3)H]Gibberellin A1 applied to the leaf accumulated in the ovary and the accumulation was related to the growth response. These experiments show that GA applied to the leaf in high enough concentration is translocated to the ovary. Emasculated ovaries on decapitated pea plants develop without application of growth hormones. When [(3)H] GA1 was applied to the leaf adjacent to the ovary a substantial amount of radioactivity accumulated in the growing shoot of intact plants. In decapitated plants, however, this radioactivity was mainly found in the ovary. There it caused growth proportional to the accumulation of CA1. Application of LAB 150978, an inhibitor of GA biosynthesis, to decapitated plants inhibited parthenocarpic fruit development and this inhibition was counteracted by the application of GA3 (either to the fruit, or the leaf adjacent to the ovary, or through the lower cut end of the stem). All evidence taken together supports the view that parthenocarpic pea fruit development on topped plants depends on the import of gibberellins or their precursors, probably from the vegetative aerial parts of the plant. PMID- 24221932 TI - Cytometric analysis of growth-regulator-dependent transcription and cell-cycle progression in Petunia protoplast cultures. AB - Acridine orange simultaneously stains DNA and RNA. Using flow cytometry, synthesis of these nucleic acids can be related throughout a culture time-course. This technique has been used with nuclei isolated from Petunia hybrida protoplasts during 48 h of culture. Nuclear RNA content has been evaluated with respect to DNA levels, namely the cell-cycle phase.Nuclear RNA synthesis was not dependent upon exogeneous hormones during the first 18 h of culture, but either auxin (2,4-dichlorophenoxyacetic acid, 2,4-D) or cytokinin (N(6)-benzyladenine) were necessary for entry into the S phase. Cytokinin alone could stimulate maximal RNA synthesis within each cell-cycle phase up to 24 h. In complete medium, DNA synthesis only began from a phase "G1B" having substantial RNA, although a subnormal amount of RNA (in protoplasts cultivated only with 2,4-D) did not prevent protoplast entry into the S phase. However, both hormones were necessary for highest RNA levels and G2 frequencies after 48 h. As in mammalian cells, the mean RNA level in plant 4C nuclei is double that of 2C nuclei. G2 nuclei are larger than G1 nuclei, but upon activation G1 nuclei in fact diminsh in size.This study aimed to identify restriction points in the cell cycle as affected by growth regulators and the specific synthesis of nucleic acids. For example, the RNA levels induced by N(6)-benzyladenine, although similar to those in complete medium, were not sufficient to induce mitosis. Conversely, 2,4-D action was probably limited by low nucleotide synthesis in the absence of cytokinin. PMID- 24221933 TI - Identification of a monoclonal antibody to abscission tissue that recognises xylose/fucose-containing N-linked oligosaccharides from higher plants. AB - Monoclonal antibodies raised against extracts of the rachis abscission zone of Sambucus nigra L. were selected for high reactivity towards abscission-zone proteins. One antibody (YZ1/2.23) has been shown to cross-react, by both indirect and competition enzyme-linked immunosorbent assay and by Western blotting, with a number of plant enzymes including horseradish peroxidase, rice alpha-glucosidase, almond beta-glucosidase and the lectins from Phaseolus vulgaris and Erythrina cristagalli.The major N-linked oligosaccharide isolated from horseradish peroxidase has the sequence Manalpha 3(Manalpha6)(Xylbeta2)Manbeta4GlcNAcbeta4(Fucalpha3) GlcNAc. This oligosaccharide was found to be a potent inhibitor of the binding of YZ1/2.23 to the intact glycoprotein. The common determinant is therefore contained within this structure. PMID- 24221934 TI - Oligosaccharide side chains of wall molecules are essential for cell-wall lysis in Chlamydomonas reinhardtii. AB - The glycoproteins of the cell walls of Chlamydomonas are lysed during the reproductive cycle by proteases (autolysins) which are specific for their substrates. The autolysin which digests the wall of sporangia to liberate the zoospore daughter cells in the vegetative life cycle is a collagenase-like enzyme which attacks only selected domains in its wall substrates containing (hydroxy) proline clusters. Cell-wall fractions obtained by salt-extraction (NaClO4) and oxidizing agents (NaClO2) and the insoluble residue were tested as substrates. The most-crosslinked insoluble inner part of the wall is the best substrate for the sporangia autolysin. Oligosaccharides obtained from the insoluble cell-wall fraction of sporangia by hydrolysis with Ba(OH)2 inhibit autolysin action. We conclude that the oligosaccharide side chains of wall substrates are essential for forming the reactive enzyme-substrate complex. PMID- 24221935 TI - Influence of cell turgor on sucrose partitioning in potato tuber storage tissues. AB - Sucrose uptake and partitioning in potato (Solanum tuberosum L.) tuber discs were examined under a range of mannitol and ethylene-glycol concentrations. Mannitol caused the same changes in turgor over a wide range of incubation periods (90 min 6 h), indicating that it did not penetrate the tissue. In comparison, ethylene glycol reduced turgor losses but did not eliminate them, even after 6 h. Between 100 mM and 300 mM mannitol, turgor fell by 350 kPa, compared with 35 kPa in ethylene glycol. Uptake experiments in mannitol alone showed that total sucrose uptake was strongly correlated with both osmotic potential and with turgor potential. In subsequent experiments sucrose uptake and partitioning were examined after 3 h equilibration in 100 mM and 300 mM concentrations of mannitol and ethylene glycol. Total sucrose uptake and the conversion of sucrose to starch were enhanced greatly only at 300 mM mannitol, indicating an effect of turgor, rather than osmotic potential on sucrose partitioning. The inhibitors p chloromercuribenzenesulfonic acid and carbonylcyanide m-chlorophenylhydrazone (CCCP) both reduced sucrose uptake, but in quite different ways. p Chloromercuribenzenesulfonic acid reduced total sucrose uptake but did not affect the partitioning of sucrose to starch. By contrast, CCCP inhibited total uptake and virtually eliminated the conversion of sucrose to starch. Despite this, sucrose uptake in the presence of CCCP continued to increase as the mannitol concentration increased, indicating an increase in passive transport at higher mannitol concentrations. Increased sucrose uptake above 400 mM mannitol was shown to be the result of uptake into the free space. The data show that starch synthesis is optimised at low but positive turgors and the relation between sucrose partitioning and the changing diurnal water relations of the tuber are discussed. PMID- 24221936 TI - Proteinase inhibitors I and II in fruit of wild tomato species: Transient components of a mechanism for defense and seed dispersal. AB - The juice of unripe fruit from a wild species of tomato, Lycopersicon peruvianum (L.) Mill., LA 107, contains over 50% of its soluble proteins as the sum of two proteinase inhibitors. These are the highest levels of proteinase inhibitors and highest percentage of soluble proteins as proteinase inhibitors of any plant or animal tissue found to date. Fruit of the modern tomato, L. esculentum Mill., contains only negligible quantities of the two inhibitors. The two proteinase inhibitors in the fruit of L. peruvianum are members of the Inhibitor I and II families previously found in potato tubers and in leaves of wounded potato and tomato plants. The levels of the two inhibitors in the unripe fruit decrease significantly during ripening. Unripe fruit from other wild Lycopersicon species such as L. parviflorum Rick, Kesicki, Fobes et Holle, L. hirsutum Humb. et Bonpe., L. pimpinellifolium Mill., and other lines of L. peruvianum contain moderate levels of the inhibitors that also decrease during ripening. Another wild tomato species, L. pennellii Corr., is similar to L. esculentum in not containing the two proteinase inhibitors in either unripe or ripe fruit. The transient levels of the inhibitors in fruit of wild species indicate that they are present in unripe fruit as defensive chemicals against insects, birds or small mammals and their disappearance during ripening may render them edible to facilitate seed dispersal. High levels of mRNAs coding for Inhibitors I and II in unripe fruit of L. peruvianum, LA 107, indicate that strong promoters may regulate the developmentally expressed proteinase-inhibitor genes in tomato fruit that may have a substantial potential for use in genetic-engineering experiments to enhance the production of large quantities of proteinase inhibitors or other proteins in field tomatoes. PMID- 24221937 TI - Production of gibberellins and indole-3-acetic acid by Rhizobium phaseoli in relation to nodulation of Phaseolus vulgaris roots. AB - Similar ranges of gibberellins (GAs) were detected by high-performance liquid chromatography (HPLC)-immunoassay procedures in ten cultures of wild-type and mutant strains of Rhizobium phaseoli. The major GAs excreted into the culture medium were GA1 and GA4. These identifications were confirmed by combined gas chromatographymass spectrometry. The HPLC-immunoassays also detected smaller amounts of GA9- as well as GA20-like compounds, the latter being present in some but not all cultures. In addition to GAs, all strains excreted indole-3-acetic acid (IAA) but there was no obvious relationship between the amounts of GA and IAA that accumulated. The Rhizobium strains studied included nod (-) and fix (-) mutants, making it unlikely that the IAA- and GA-biosynthesis genes are closely linked to the genes for nodulation and nitrogen fixation.The HPLC-immunoassay analyses showed also that nodules and non-nodulated roots of Phaseolus vulgaris L. contained similar spectra of GAs to R. phaseoli culture media. The GA pools in roots and nodules were of similar size, indicating that Rhizobium does not make a major contribution to the GA content of the infected tissue. PMID- 24221938 TI - The metabolism of exogenous hydroxyproline by gametophytes of Plagiochila arctica Bryhn et Kaal. (Hepaticae). AB - The metabolic fate of free 4-hydroxyproline (Hyp), dual-labeled in specific positions, supplied to axenically cultured gametophytes of Plagiochila arctica was found to be complex. It could enter into at least three pathways, and the one that predominated depended on the concentration supplied. At low concentrations (i.e., 1 MUM), free Hyp was mostly converted to proline (Pro) by a pathway in which pyrroline-5-carboxylate is the most probable intermediate. Lesser amounts entered a pathway(s) in which hydrogen was lost from the 3(2) carbon. And a small amount was directly incorporated into protein. At the higher concentrations that have been found to desuppress leaf and branch development in P. arctica the proportion of the labeled Hyp converted to Pro was markedly diminished and the proportion that was directly incorporated into peptide linkage was increased. This direct incorporation of Hyp into protein may be closely related to the ability of Hyp to relieve suppression of ventral leaves in leafy liverworts. the suppression-desuppression phenomenon is thought to involve cell surface and-or extracellular matrix proteins. PMID- 24221939 TI - Feedback regulation of nodule formation in alfalfa. AB - When high dosages of wild-type Rhizobium meliloti RCR2011 were inoculated at two different times, 24 h apart, onto either the primary roots of alfalfa (Medicago sativa L.) seedlings or onto lateral roots on opposite sides of a split-root system, the number of nodules generated by the second inoculum was much smaller than the number generated by the first inoculum. These results provide evidence that alfalfa has an active, systemic mechanism for feedback control of nodulation. Non-nodulating mutants and delayed, weakly nodulating mutants did not elicit a discernable suppression of nodulation by subsequently inoculated wild type cells. An appreciable number of Rhizobium infections thus seem required to elicit the suppressive response. Mutants in nodulation regions IIb and IIa nodulated extensively in the initially susceptible region of the root, but nodule initiation by these mutants was 100-1000 times less efficient, respectively, than the parent. Nodules formed by these mutants emerged 1 d later than normal. The IIb mutants elicited a relatively strong suppression of nodulation in younger parts of the root, but region-IIa mutants elicited only a weak response. These results indicate that elicitation of the regulatory response need not be proportional to nodule formation and imply that genes in region IIa play an important role in elicitation. At high dosages, the region-II mutants induced the development of thick, short roots in a considerably higher percentage of plants than the wild-type bacteria. Nodules generated by wild-type isolates and region II mutants did not emerge in strict acropetal sequence, probably because some infections developed more slowly than others. Prior exposure of the root to non nodulating mutants resulted in nodulation by the parent in regions of the root otherwise too mature to be susceptible, indicating that exposure to these mutants may affect the sequence of root development. PMID- 24221940 TI - Different properties of two types of auxin-binding sites in membranes from maize coleoptiles. AB - Two types of auxin-binding sites (sites I and II) in membranes from maize (Zea mays L.) coleoptiles were characterized. Site I was a protein with a relative molecular mass of 21 000, and the distribution of site I protein on sucrose density gradient fractionation coincided with that of NADH-cytochrome-c reductase (EC 1.6.99.3), a marker enzyme of the endoplasmic reticulum. Immunoprecipitation and immunoblotting studies showed that the content of site I protein in maize coleoptiles was approx. 2 MUg.(g FW)(-1). Site II occurred in higher-density fractions and also differed immunologically from site I. Site I was present at the early developmental stage of the coleoptile and increased only twice during coleoptile growth between day 2 and 4. Site II activity was low at the early stage and increased more substantially between day 3 and 4, a period of rapid growth of the coleoptile. Both sites decreased concurrently after day 4, followed by a reduction in the growth rate of the coleoptile. Coleoptiles with the outer epidermis removed showed a lower site I activity than intact coleoptiles, indicating that site I was concentrated in the outer epidermis. Site II, in contrast, remained constant after removal of the outer epidermis. The results indicate that site I is not a precursor of site II and that the two sites are involved in different cellular functions. PMID- 24221942 TI - Effect of broodstock diets on lipid classes and their fatty acid composition in eggs of gilthead sea bream (Sparus aurata L.). AB - Total lipid content, total lipid fatty acids, lipid classes and their fatty acid compositions were studied in eggs of gilthead sea bream from two different broodstocks.The two broodstock diets used had the same total lipid content, but differed with respect to their fatty acid levels. The lipid class composition of eggs from different origins was not significantly different. The predominant polar lipids were phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, and the main neutral lipid classes were cholesterol esters and triacylglycerols.The fatty acid composition of total lipids and main lipid classes in the two groups of eggs showed marked differences, reflecting the influence of fatty acid levels in the broodstock diets. PMID- 24221943 TI - Effect of broodstock diets on total lipids and fatty acid composition of larvae of gilthead sea bream (Sparus aurata L.) during yolksac stage. AB - Total lipid content and total lipid fatty acid compositions were studied in larvae at the yolksac stage of gilthead sea bream from two different broodstocks. The two broodstock diets had the same total lipid content but were different with respect to their fatty acid levels.There were differences in the fatty acid composition of total lipids in the two groups of larvae, reflecting the influence of fatty acid levels in the diets fed to the broodstock. The main fatty acids in both larvae lots during yolksac stage were 16:0, 18:1n-9 and 22:6n-3.The desaturation index Deltax = [P + Sigma (n - x) - Sigma (n - x) diet]/P allowed the determination of the relative importance of the Delta9, Delta6, Delta5 and Delta4 desaturations during the egg and larval yolksac stages.The levels of total lipid fatty acids in eggs and larvae during yolksac period were almost constant and very low desaturation and elongation activities were apparent.A competitive inhibition was observed between the fatty acids of the n-6 series with respect to the ones of the n-3 series in those eggs and larvae from broodstock whose diet contained a high proportion of linoleic acid and its derivatives. PMID- 24221941 TI - A Drosophila melanogaster model of diastolic dysfunction and cardiomyopathy based on impaired troponin-T function. AB - RATIONALE: Regulation of striated muscle contraction is achieved by Ca2+ dependent steric modulation of myosin cross-bridge cycling on actin by the thin filament troponin-tropomyosin complex. Alterations in the complex can induce contractile dysregulation and disease. For example, mutations between or near residues 112 to 136 of cardiac troponin-T, the crucial TnT1 (N-terminal domain of troponin-T)-tropomyosin-binding region, cause cardiomyopathy. The Drosophila upheld(101) Glu/Lys amino acid substitution lies C-terminally adjacent to this phylogenetically conserved sequence. OBJECTIVE: Using a highly integrative approach, we sought to determine the molecular trigger of upheld(101) myofibrillar degeneration, to evaluate contractile performance in the mutant cardiomyocytes, and to examine the effects of the mutation on the entire Drosophila heart to elucidate regulatory roles for conserved TnT1 regions and provide possible mechanistic insight into cardiac dysfunction. METHODS AND RESULTS: Live video imaging of Drosophila cardiac tubes revealed that the troponin-T mutation prolongs systole and restricts diastolic dimensions of the heart, because of increased numbers of actively cycling myosin cross-bridges. Elevated resting myocardial stiffness, consistent with upheld(101) diastolic dysfunction, was confirmed by an atomic force microscopy-based nanoindentation approach. Direct visualization of mutant thin filaments via electron microscopy and 3-dimensional reconstruction resolved destabilized tropomyosin positioning and aberrantly exposed myosin-binding sites under low Ca2+ conditions. CONCLUSIONS: As a result of troponin-tropomyosin dysinhibition, upheld(101) hearts exhibited cardiac dysfunction and remodeling comparable to that observed during human restrictive cardiomyopathy. Thus, reversal of charged residues about the conserved tropomyosin-binding region of TnT1 may perturb critical intermolecular associations required for proper steric regulation, which likely elicits myopathy in our Drosophila model. PMID- 24221944 TI - The purification and partial characterization of carp, Cyprinus carpio, vitellogenin. AB - A procedure is described for the isolation of intact vitellogenin (c-VTG) from the carp, Cyprinus carpio. VTG was induced in juvenile females using oestradiol 17beta and purified from the plasma using a combination of gel-filtration chromatography on Sepharose 6B and ion exchange chromatography on DEAE-cellulose. Purification procedures were conducted at low temperatures (below 9 degrees C) in the presence of the proteolytic enzyme inhibitor aprotinin to prevent degradation. Intact c-VTG had an apparent molecular mass of 390,000 Daltons, but when extracted from plasma in the absence of aprotinin it underwent proteolysis into at least 2 protein fragments (apparent molecular masses of 230,000 and 96,000 Daltons), showing an instability of the native dimer. An amino acid analysis of c-VTG showed that its composition was almost identical to goldfish VTG, a species closely allied to the true carps and also similar to other oviparous vertebrate VTGs. Collectively, these data indicate that using these purification procedures VTG from carp, and probably other teleost species, can be isolated in an intact, highly purified form. PMID- 24221945 TI - Estrogen treatment and its influence on protein synthesis and amino acid metabolism in Zoarces viviparus (L) males. AB - Overall protein synthesis was studied in estradiol-treated and control Zoarces viviparus males. Significant increases in total RNA, the RNA:DNA and the RNA:protein ratios in the liver were correlated with a 6-fold increase in total calcium levels in the plasma, indicating increased protein synthetic activity and the presence of circulating vitellogenin respectively in the induced males. The time-course incorporation of (14)C-phenylalanine into protein in a cell free liver system showed a linear increase during the first 30 min after poly (U) was added to the incubation medium in control as well as in the estradiol-treated males. The incorporation rate in the induced liver, however, was increased significantly above the level of the control livers. Estradiol-treatment altered the concentration of most amino acids in the plasma and a few in the liver with particular marked effects on alanine and tyrosine in the plasma and glutamate in the liver. PMID- 24221946 TI - The development of a radioimmunoassay for carp, Cyprinus carpio, vitellogenin. AB - The development of an easily - performed and robust radioimmunoassay (RIA) to carp, Cyprinus carpio, vitellogenin (c-VTG) is described. Purified c-VTG was iodinated using Iodogen. The resulting c-VTG label was useful for up to 60 days. High titre antibodies were raised in rabbits to the purified c-VTG. The practical operating range of the c-VTG RIA was between 2 and 200 ng. ml(-1). VTG was detected in plasma from all female mirror carp investigated, and all plasmas diluted parallel to the standard. The plasma VTG level in female carp increased concomitantly with the GSI; levels increasing from the ng. ml(-1) level in juveniles to a maximum of 1 mg. ml(-1) in fully mature females. VTG level was a far more sensitive index of the degree of sexual development than was GSI. In males, blood levels of VTG were always undetectable. Vitellogenic plasma from all subspecies of C. carpio (e.g. mirror, common, Koi) diluted parallel to the standard, as did blood from most other female cyprinids, such as the roach (Rutilis rutilis), bream (Abramis brama), and dace (Leuciscus leuciscus), but not all. These results suggest that the structure of VTG is highly conserved within this family. However, plasma from vitellogenic salmonids did not cross-react in the RIA. The relationship between plasma VTG and calcium levels was studied in both carp and rainbow trout. In rainbow trout it was found that plasma calcium levels do not rise above basal levels until the VTG level exceeds about 1 mg. ml( 1), and therefore in this species it is only useful as an indicator of the degree of ovarian development in the later stages of the reproductive cycle. In the carp, however, and probably other cyprinids, blood VTG levels do not appear to naturally exceed about 1 mg.ml(-1), and plasma calcium levels are not suitable as an indirect measure of the VTG level. PMID- 24221947 TI - Regional distribution of microsomal xenobiotic and steroid metabolism in kidney microsomes from rainbow trout. AB - The regional distribution of microsomal cytochrome P-450-mediated reactions with exogenous and endogenous substrates in the kidney of rainbow trout was studied. The cytochrome P-450-dependent 7-ethoxyresorufin- and 7-ethoxycoumarin-0 deethylase activities were significantly higher (3-4 and 10-14 fold, respectively) in the trunk kidney than in the head kidney, whereas ethylmorphine N-demethylase activity was evenly distributed along the kidney. The microsomal cytochrome P-450-dependent steroid hydroxylases and steroid reducing enzymes when using androstenedione as substrate also exhibited a regional distribution in trout kidney. The 6beta- and 16-hydroxylase activities as well as the 5alpha reductase and 17 hydroxysteroid oxidoreductase activities were higher in the anterior part of the trunk kidney than in the head kidney and posterior trunk kidney. PMID- 24221948 TI - Does Amia Calva aestivate? AB - During gradual air exposure, Amia calva show no reduction in oxygen consumption, no increase in plasma urea levels or in urea excretion. Blood pH remains constant, and plasma total CO2, PCO 2, HCO3 (-). total ammonia and NH3 concentrations all rise significantly. Exposure to 923 MUmol/l NH4Cl does not elicit an increase in urea production or airbreathing. Aquatic hypoxia without access to air does not cause a reduction in aerobic metabolism, and moderate levels result in death. These results suggest that Amia are incapable of aestivation, due to an inability to detoxify ammonia to urea and reduce metabolism, and die following three to five days of air exposure. PMID- 24221949 TI - Growth hormone secretion during longterm incubation of the pituitary of the Japanese eel, Anguilla japonica. AB - Growth hormone (GH) secretion from organ-cultured pituitaries of the eel (Anguilla japonica) was studied during incubation in a defined medium for 2 weeks, using a homologous radioimmunoassay which does not distinguish between the two molecular forms of eel GH. The total amount of GH secreted increased gradually during the incubation period; so that the amount of GH released on day 14 was about 30 times greater than that on day 1. On day 14, the proportion of GH released relative to the total amount of GH present (the sum of GH released into the medium and residual content in the pituitary) was 96% and the amount produced on day 14 was 4 times greater than the content in the unincubated pituitary. Somatostatin (SRIF, 1.8 * 10(-7) M) inhibited the increase in GH release. On day 7, the proportion of GH released by pituitaries treated with SRIF (28%) was less than that released by the control pituitary (91%). There was no significant difference in GH release between the pituitaries incubated in isotonic medium (300 mOsm) and those in hypotonic medium (240 mOsm) for 2 weeks except for the first 3 days, when the pituitaries in hypotonic medium secreted significantly greater amounts of GH than those incubated under isotonic condition. Hypertonic medium (350 mOsm) had no effect on GH release except for significant inhibition on days 6 and 14. When secretion of the two forms of GH (GH I and II) was examined after separation by polyacrylamide gel electrophoresis followed by densitometry, slightly more GH I tended to be secreted than GH II during the culture period, although the effects of SRIF and osmolality of the media on GH I release were similar to those on GH II. It is concluded that GH secretion and production in the eel is mainly under the inhibitory control of hypothalamus, and that osmolality has a minimum influence on the GH release. PMID- 24221950 TI - Changes in serum thyroxine and triiodothyronine concentrations during metamorphosis of the Southern Hemisphere Lamprey Geotria australis, and the effect of propylthiouracil, triiodothyronine and environmental temperature on serum thyroid hormone concentrations of ammocoetes. AB - Serum thyroid hormone concentrations were measured during the seven stages of metamorphosis (1-7) of the southern hemisphere lamprey, Geotria australis. The respective mean concentrations +/- SEM of serum thyroxine (T4) and triiodothyronine (T3) fell from 31.73 +/- 4.09 and 5.06 +/- 0.70 nM in large ammocoetes sampled in February, at the time when metamorphosis was initiated, to 4.54 +/- 0.36 and 1.03 +/- 0.12 nM at stage 5. Although there was a small, but significant, recovery of serum T4 concentrations during stages 6 and 7, no such corresponding statistically significant rise occurred in serum T3 concentrations.Serum thyroid hormone concentrations in ammocoetes sampled during the period when metamorphosis was taking place, exhibited a marked seasonal increase between February and May-June (late autumn/early winter); serum T3 and T4 concentrations peaked in May-June and were, respectively, > 2 fold and > 8 fold higher than those recorded for samples in late February (mid summer). By mid July the serum T4 and T3 levels had declined from the peak values.Ammocoetes taken from streams at 16 degrees C in June and acclimated to aquaria water at 25 degrees C or 6 degrees C had significantly lower serum T3 and T4 concentrations at the higher temperature, and also a lower serum T4, but not T3 concentration, at the lower temperature.Treatment of separate groups of ammocoetes with either propylthiouracil or T3 for 70 days significantly depressed and raised respectively, the serum thyroid hormone and hepatic T3 concentrations and caused significant changes in the body weight, but did not induce the onset of metamorphosis. PMID- 24221951 TI - Tissue-specific distribution of amylase in the mosquitofish (Gambusia affinis holbrooki). AB - Tissue-specific expression of alpha-amylase (E.C.3.2.1; alpha 1,4-glucan-4 glucano-hydrolase) was studied in the mosquitofish (Gambusia affinis holbrooki). Gut activity patterns, immunohistochemical distribution in the hepatopancreas and tissue-specific activities and amount of amylase protein were characterized. In the gut, activity was observed all along the gut and no variation in this pattern was observed in individuals from two natural populations. In the hepatopancreas, amylase is found in pancreatic tissue. Highest amylase activity was observed in gut tissue but highest amount of amylase protein was found in the hepatopancreas. PMID- 24221952 TI - Referees of articles submitted to the Journal in 1989. PMID- 24221953 TI - A Motivational Physical Activity Intervention for Improving Mobility in Older Korean Americans. AB - There has been limited empirical support for interventions designed to promote physical activity targeting mobility in racially diverse older adults. This study aims to examine the effects of a Motivational Physical Activity Intervention (MPAI) on social resource, behavioral change process, physical activity, and mobility variables in sedentary older Korean Americans. A quasi-experimental, repeated-measure, pre- and post-tests design was used. Sixty-four community dwelling, sedentary older Korean Americans (n = 33 for MPAI group, n = 31 for Attention Control group) participated in the study. There were significant improvements in social resources, including social support from family and friends; behavioral change process variables, including self-efficacy; motivational appraisal; and self-regulation for physical activity. There were significant intervention effects on physical activity, walking endurance, and flexibility. The MPAI is supported as improving mobility and physical activity, as well as increasing motivation for physical activity in older Korean Americans. PMID- 24221954 TI - Caregiving Choice and Emotional Stress Among Cancer Caregivers. AB - Caring for a relative or friend with cancer may be highly demanding and emotionally burdensome. Theory suggests that personal characteristics of a caregiver may contribute directly to a caregiver's emotional health. An underexplored variable is a caregiver's perception of choice in providing care to a relative or friend. Thus, this study sought to characterize perceived choice in providing care among family cancer caregivers and examine its association with emotional stress. This study is a secondary analysis of cross-sectional telephone interviews of 1,247 family caregivers, which included 104 cancer caregivers. The findings indicated that a high majority of cancer caregivers expressed elevated emotional stress. Most caregivers perceived themselves to have had a choice in providing care; however, a perceived lack of choice in providing care was significantly associated with greater emotional stress. Assessing clinical and policy-related strategies for alleviating concerns related to choice may be of value in the cancer context. PMID- 24221955 TI - Teaching smoking cessation to future nurses: Quebec educators' beliefs. AB - Smoking cessation strategies are barely discussed in nursing education programs, even though initial education shapes how future professionals practice their profession. The aim of this research is to describe the practices, attitudes, and beliefs of nursing educators of Quebec with regard to smoking cessation strategies in initial nursing education. A descriptive design was chosen along with an online questionnaire. A total of 278 educators (20.8%) participated in the survey. Although educators recognize the importance of incorporating smoking cessation strategies into their teaching practice, they allocate an average of only one hour per year to the topic. Tobacco use is addressed mostly in terms of risk factors, with little focus on how to help patients quit. The perceived obstacles are related to false beliefs and a lack of knowledge. The results of this study demonstrate the need to raise educators' awareness of the importance of incorporating smoking cessation strategies into classroom teaching. PMID- 24221956 TI - Integrated platform for production and purification of human pluripotent stem cell-derived neural precursors. AB - Human pluripotent stem cells (hPSCs) are a promising source of cells for clinical applications, such as transplantation of clinically engineered tissues and organs, and drug discovery programs due to their ability to self-renew and to be differentiated into cells from the three embryonic germ layers. In this study, the differentiation of two hPSC-lines into neural precursors (NPs) was accomplished with more than 80% efficiency, by means of the dual-SMAD inhibition protocol, based on the use of two small molecules (SB431542 and LDN193189) to generate Pax6 and Nestin-positive neural entities. One of the major hurdles related to the in vitro generation of PSC-derived populations is the tumorigenic potential of cells that remain undifferentiated. These remaining hPSCs have the potential to generate teratomas after being transplanted, and may interfere with the outcome of in vitro differentiation protocols. One strategy to tackle this problem is to deplete these "contaminating" cells during the differentiation process. Magnetic activated cell sorting (MACS) was used for the first time for purification of hPSC-derived NPs after the neural commitment stage using anti-Tra 1-60 micro beads for negative selection of the unwanted hPSCs. The depletion had an average efficiency of 80.4 +/- 5% and less than 1.5% of Tra-1-60 positive cells were present in the purified populations. After re-plating, the purified neural precursors maintained their phenotype, and the success of the preparative purification with MACS was further confirmed with a decrease of 94.3% in the number of Oct4-positive proliferating hPSC colonies. Thus, the integration of the MACS depletion step with the neural commitment protocol paves the way towards the establishment of a novel bioprocess for production of purified populations of hPSC-derived neural cells for different applications. PMID- 24221957 TI - High-performance low-cost back-channel-etch amorphous gallium-indium-zinc oxide thin-film transistors by curing and passivation of the damaged back channel. AB - High-performance, low-cost amorphous gallium-indium-zinc oxide (a-GIZO) thin-film transistor (TFT) technology is required for the next generation of active-matrix organic light-emitting diodes. A back-channel-etch structure is the most appropriate device structure for high-performance, low-cost a-GIZO TFT technology. However, channel damage due to source/drain etching and passivation layer deposition has been a critical issue. To solve this problem, the present work focuses on overall back-channel processes, such as back-channel N2O plasma treatment, SiOx passivation deposition, and final thermal annealing. This work has revealed the dependence of a-GIZO TFT characteristics on the N2O plasma radio frequency (RF) power and frequency, the SiH4 flow rate in the SiOx deposition process, and the final annealing temperature. On the basis of these results, a high-performance a-GIZO TFT with a field-effect mobility of 35.7 cm(2) V(-1) s( 1), a subthreshold swing of 185 mV dec(-1), a switching ratio exceeding 10(7), and a satisfactory reliability was successfully fabricated. The technology developed in this work can be realized using the existing facilities of active matrix liquid-crystal display industries. PMID- 24221958 TI - Land use impact on soil quality in eastern Himalayan region of India. AB - Quantitative assessment of soil quality is required to determine the sustainability of land uses in terms of environmental quality and plant productivity. Our objective was to identify the most appropriate soil quality indicators and to evaluate the impact of six most prevalent land use types (natural forestland, cultivated lowland, cultivated upland terrace, shifting cultivation, plantation land, and grassland) on soil quality in eastern Himalayan region of India. We collected 120 soil samples (20 cm depth) and analyzed them for 29 physical, chemical, and biological soil attributes. For selection of soil quality indicators, principal component analysis (PCA) was performed on the measured attributes, which provided four principal components (PC) with eigenvalues >1 and explaining at least 5% of the variance in dataset. The four PCs together explained 92.6% of the total variance. Based on rotated factor loadings of soil attributes, selected indicators were: soil organic carbon (SOC) from PC-1, exchangeable Al from PC-2, silt content from PC-3, and available P and Mn from PC-4. Indicators were transformed into scores (linear scoring method) and soil quality index (SQI) was determined, on a scale of 0-1, using the weighting factors obtained from PCA. SQI rating was the highest for the least-disturbed sites, i.e., natural forestland (0.93) and grassland (0.87), and the lowest for the most intensively cultivated site, i.e., cultivated upland terrace (0.44). Ratings for the other land uses were shifting cultivation (0.60) > cultivated low land (0.57) > plantation land (0.54). Overall contribution (in percent) of the indicators in determination of SQI was in the order: SOC (58%) > exch. Al (17.1%) > available P (8.9%) > available Mn (8.2%) > silt content (7.8%). Results of this study suggest SOC and exch. Al as the two most powerful indicators of soil quality in study area. Thus, organic C and soil acidity management holds the key to improve soil quality under many exploitatively cultivated land use systems in eastern Himalayan region of India. PMID- 24221959 TI - The relationship between chemical elements in soil and whole blood, and fluorosis induced by coal-fired pollution. AB - To study the relationship between chemical elements in soil and whole blood, and fluorosis induced by coal-fired pollution, ecological and case-control studies were carried out. We determined the concentrations of 11 chemical elements and pH values in soil in two fluorosis-affected counties in Chongqing, China, and analyzed the correlation between these values and prevalence of dental fluorosis. Ni, I, F, Hg, and pH values positively correlated with fluorosis prevalence (P < 0.05); these soil parameters may be related to coal-fired pollution fluorosis. Cu, Zn, Ca, Mg, and Fe concentrations in whole blood, and fluoride levels in urine of residents in epidemic and non-epidemic areas were determined. Cu, Zn, Mg, and Fe levels of the children in the case group were lower than those of the children in the external control group; urine fluoride level in the children in the case group was higher than that of the children in the internal and external control groups (P < 0.05). The levels of Mg, Fe, and urine fluoride were higher in the case adult group than in the internal adult control group (P < 0.05). Anti fluoride elements were deficient in endemic areas. PMID- 24221960 TI - Transapical aortic valve implantation and minimally invasive off-pump bypass surgery. AB - Transcatheter aortic valve implantation (TAVI) has gained increasing popularity for high-risk patients with symptomatic aortic valve stenosis. A concomitant coronary artery disease leads to a complicated management and an increased perioperative risk. This case report describes the successful total arterial coronary revascularization of the left anterior descending and the left marginal branch of the circumflex artery utilizing the left internal mammary artery (LIMA) and left radial artery in off-pump technique in combination with the transapical transcatheter aortic valve implantation via minimally invasive anterolateral access in the fifth intercostal space. PMID- 24221962 TI - Micro-electrospray mass spectrometry: Ultra-high-sensitivity analysis of peptides and proteins. AB - A "micro-electrospray" ionization source has been developed that markedly increases the sensitivity of the conventional electrospray source. This was achieved by optimization of the source to accommodate nanoliter flow rates from 300 to 800-nL/min spraying directly from a capillary needle that, for the analysis of peptides, contained C18 liquid chromatography packing as an integrated concentration-desalting device. Thus, a total of 1 fmol of methionine enkephalin was desorbed from the capillary column spray needle, loaded as a 10 MUL injection of 100-amol/MUL solution. The mass spectrum showed the [M + H](+) ion at m/z 574.2 with a signal-to-noise ratio of better than 5:1 from a chromatographic peak with a width of about 12 s. A narrow range (15-u) tandem mass spectrum was obtained for methionine enkephalin from the injection of 500 amol, and a full-scan tandem-mass spectrum was obtained from 50 fmol. For proteins, the average mass measurement accuracy was approximately 100-200 ppm for the injection of 2.5 fmol of apomyoglobin and 20-40 ppm for 200 fmol. Carbonic anhydrase B and bovine serum albumin showed similar mass measurement accuracies. PMID- 24221961 TI - Trends in cancer-targeted antibody-drug conjugates. AB - Better knowledge of engineered antibodies and tumour biology has led to the development of novel targeted therapies, such as antibody-drug conjugates (ADCs). ADCs combine a monoclonal antibody, directed toward specific antigen highly expressed on the cancer cell, to potent cytotoxic drug through a stable linker. ADCs are designed to bind selectively to cancer cells and to deliver cytotoxic drugs into the cancer cell, which may preserve normal cells. ADCs should be stable and non-toxic in circulation. Upon binding to antigen, ADCs are internalized by different processes, followed by the intracellular release of an active form of the cytotoxic drug, which in turn kills the cancer cell. This technology has the potential to further improve the anticancer activity while limiting toxicity. First results from ongoing clinical trials are encouraging. Favourable pharmacokinetic profile was observed showing good stability in circulation. Clinical studies demonstrated that ADCs provide clinical efficacy with an acceptable safety profile. Objective responses and clinical benefits were demonstrated with the investigated ADCs. Major toxicities frequently associated to chemotherapy were barely or not reported with ADCs. Taken together, ADCs may become the new wave of anticancer drugs in the future. PMID- 24221963 TI - A study of the thermal denaturation of ribonuclease S by electrospray ionization mass spectrometry. AB - The thermal stability of ribonuclease S (RNase S), an enzymatically active noncovalent complex composed of a 2166-u peptide (S-peptide) and a 11,534-u protein (S-protein), was investigated by electrospray ionization mass spectrometry (ESI-MS) and capillary electrophoresis ESI-MS (CE-ESI-MS). The intensities of peaks corresponding to the RNase S complex were inversely related to both the applied nozzle-skimmer (or capillary-skimmer) voltage bias in the atmosphere-vacuum interface and the temperature of the RNase S solution. By using a heated metal capillary-skimmer interface and a room temperature solution of RNase S, the intensities of RNase S molecular ion peaks were observed to decrease with increasing metal capillary temperature. Mass spectrometric studies with both the nozzle-skimmer and capillary-skimmer interface designs allowed determination of phenomenological enthalpies for dissociation of the RNase S complex in both solution and for the electrosprayed microdroplet-gas phase species. Intact RNase S complex could also be detected with CE-ESI-MS separations by using a 10-mM ammonium bicarbonate (pH 7.9) solution as the electrophoretic buffer. These studies provide new insights into the stability of multiply charged noncovalent complexes in the gas phase and the mass spectrometric conditions required for such studies, and suggest that information regarding solution properties can be obtained by ESI-MS. PMID- 24221964 TI - Gas-phase hydrogen/deuterium exchange as a molecular probe for the interaction of methanol and protonated peptides. AB - The gas-phase hydrogen/deuterium (HID) exchange kinetics of several protonated amino acids and dipeptides under a background pressure of CH3OD were determined in an external source Fourier transform mass spectrometer. H/D exchange reactions occur even when the gas-phase basicity of the compound is significantly larger (> 20 kcal/mol) than methanol. In addition; greater deuterium incorporation is observed for compounds that have multiple sites of similar basicities. A mechanism is proposed that involves a structurally specific intermediate with extensive interaction between the protonated compound and methanol. PMID- 24221965 TI - Gas-Phase studies of valinomycin-alkali metal cation complexes: attachment rates and cation affinities. AB - Reactions of laser-desorbed Na(+), K(+), Rb(+), and Cs(+) with thermally vaporized valinomycin generate metal-ligand complexes in a Fourier transform ion cyclotron resonance trapping cell, proving that complexes can form via gas-phase ion-molecule reactions. Although desorption of intact pre-formed complexes cannot be ruled out, this route appears minor. Relative rate constants for the complexation reactions show strong dependence on the charge densities of the cations. Competition experiments between valinomycin and the synthetic ionophores 18-crown-6 (18C6) and [2.2.2]-cryptand ([2.2.2]) show that valinomycin has a higher intrinsic alkali metal cation affinity than either 18C6 or [2.2.2], in contrast to the complex formation constants observed in methanol, where K+ affinities are in the order [2.2.2] > 18C6 > valinomycin. PMID- 24221966 TI - Evidence for the direct desorption of crown ether-metal ion complexes in liquid secondary Ionization Mass Spectrometry. AB - The liquid secondary ionization mass spectra of crown ether solutions and crown ether solutions containing alkali metal cations were generated. Cesium cations acted as both the primary ion beam and as a competing gas-selvedge-phase reactant. The data suggest that crown ether complexes formed in the condensed phase survive intact the fast ion bombarding event and the transition into the gas phase. The data further suggest that crown ether complexes formed in the condensed phase predominate in the ion spectrum over the corresponding complexes formed in the selvedge. PMID- 24221967 TI - Characteristics of high energy collision-induced dissociation tandem Mass Spectra of Polycyclic aromatic Hydrocarbon diolepoxide adducted peptides. AB - Polycyclic aromatic hydrocarbon (PAH) diolepoxides are known to covalently modify serum albumin and hemoglobin. Mass spectrometric techniques have proven quite useful in the characterization of the site of adduction on these proteins. To facilitate the study of PAH diolepoxide adducted peptides, model peptide adducts of benzo[a]pyrene-trans-7,8-dihydrodiol-epoxide [anti-BaP(9,10)DE] and benzo[a]anthracene-trans-8,9-dihydrodiol-10,11-epoxide [anti-BaA(10,11)DE] have been synthesized for the purpose of studying their high energy collision-induced dissociation tandem mass spectra. These spectra are dominated by ions produced from cleavage of the peptide-adduct bond with charge retention by the adducting moiety. Such ions allow for the facile identification of adducted peptides in a mixture by use of neutral loss scans. The peptide sequence can still be deduced from the data in most cases, and the site of adduction can be determined. For those peptide-adducts in which this is not possible, a charged derivative placed at the N-terminus simplifies the peptide fragmentation pattern and makes the spectrum more interpretable. PMID- 24221968 TI - Mass spectrometric analysis of nitrogen- and phosphorus-containing pesticides by liquid chromatography-Mass Spectrometry. AB - A series of nitrogen- and phosphorus-containing pesticides (amines, anilides, carbamates, phosphonates, phenylureas, sulfonylureas, and triazines) was examined by thermospray (TSP) ionization. A method is described that employs off-line and on-line solid-phase extraction and TSP liquid chromatography-mass spectrometry (LC-MS) with time-scheduled selected ion monitoring (SIM) for environmental monitoring of these pesticides in aqueous samples. SIM detection limits for the pesticides analyzed in conjunction with reversed-phase high-performance liquid chromatography range from 40 to 600 pg. In addition, methods for inducing fragmentation in thermospray LC-MS are presented. The structural information gained therefrom can be used to confirm a tentative identification. Therefore, fragmentation pathways under certain experimental conditions were investigated. Atmospheric pressure chemical ionization, electrospray, fast-atom bombardment, (252)Cf plasma desorption, and collision-activated dissociation spectra are presented for several pesticides to confirm the proposed pathways and to gain additional and complementary information. Further confirmation may be achieved by postcolumn addition of different alkylated amines to the carrier stream in the TSP operation to induce postcolumn on-line derivatization (POD) reactions in the condensed phase of the vaporizer probe with selected pesticides. Additional clustering reactions in combination with solvent-mediated chemical ionization are observed by the POD technique. Both processes can be used to enhance the structural information from TSP spectra and thus the specificity of the method. PMID- 24221969 TI - Extended theoretical considerations for Mass resolution in the resonance ejection mode of quadrupole Ion Trap Mass Spectrometry. AB - Proceeding from the pseudopotential-well approximation for ion motion in a quadrupole ion trap, mathematical expressions are derived to describe the excitation amplitude of an ion packet at a given mass-to-charge ratio. Ion neutral collisions are incorporated to describe the damping of ion trajectories and to describe the distribution of individual ion trajectories about a mean amplitude for the ion packet. The rate of increase of the amplitude during scanning is related to expressions that describe the amplitude dispersion of the ions at the time of ejection from the trap, which is operating in a resonance ejection scanning mode to describe the temporal line width of the ejected ion packet. The temporal line width is related to mass resolution under a number of different scanning conditions. Included in the discussion are considerations of the effect on resolution of the resonance excitation voltage, temperature, pressure, noise, and buffer-gas composition. An expression for the maximum possible resolution at high ion mass-to-charge ratios is developed, and these results are compared to an existing theoretical construction. The expressions derived under the pseudopotential-well approximation are further extended to high q z values and compared to experimental data previously published by two other researchers. PMID- 24221970 TI - Observation of gas-phase molecular dications formed from neutral organics in solution via qemical electron-transfer reactions by using electrospray Ionization Mass Spectrometry. AB - The first observation of organic dications formed by multiple electron loss in electrospray mass spectra is reported. The dications of beta-carotene, canthaxanthine, cobalt(II) octaethylporphyrin, and nicke(II) octaethylporphyrin were created in solution via chemical electrontransfer reactions and detected in the gas phase by electrospray ionization mass spectrometry (ES-MS) using a flow injection experiment. The analytes were injected into a flowing solvent-oxidant stream (10 MUL/min) composed of dried methylene chloride containing ~ 0.1% by volume trifluoroacetic acid and 0.1% by volume antimony pentafluoride (SbF5). The dications created in this oxidizing solvent system were preserved for detection by rapidly transferring them from the reactive solvent-oxidant system to the gas phase, where, in the absence of the solvent system, they were "long-lived" and amenable to mass analysis. This work demonstrates means to produce ions novel to ES-MS and means to detect and study by ES-MS species that are short-lived in solution. In addition, this work shows that electrospray ionization can potentially be used to generate gas-phase dications for mass spectrometric study that are difficult to produce directly from gas-phase neutrals by other ionization techniques (e.g., M(2+) from beta-carotene). PMID- 24221972 TI - The determination of an optimal waste management scenario for Kampala, Uganda. AB - The quality of the environment in the city of Kampala is deteriorating. The city needs a novel waste management approach to improve the environmental quality in its heterogeneous settlement patterns. Earlier, an integrated urban waste flow model (IUWFM) was applied to project the future waste flows and their impacts on the environment of Kampala using four waste management scenarios. These scenarios were 'business-as-usual', 'more enforcement', 'more collection' and 'proper management'. The robustness of the scenario results was determined by using a multi-criteria decision analysis. Twenty-four criteria were identified and grouped as environmental, economic, social, technological and general. Equal weights were assigned to these five sets of criteria. The four scenarios were evaluated against all criteria, and a sensitivity analysis was performed on the role of the equal weights on the choice of the scenarios. The results showed that 'proper management' scenario, which integrates diverse technologies and management programs matching with the local context, is the optimal approach to improve Kampala's environmental quality. Scenarios that emphasized more waste collection, but less resource recovery were ranked in the middle. The scenario of maintaining the status quo performed worst. Application of a mix of diverse technologies and management programs matching the local conditions is the most optimal solution to improve Kampala's environmental quality. PMID- 24221973 TI - [Nosocomial pneumonia during stress ulcer prophylaxis? - risk of nosocomial pneumonia is increased during stress ulcer prophylaxis]. PMID- 24221974 TI - [Distress among physicians in hospitals - an investigation in Baden-Wurttemberg, Germany]. AB - BACKGROUND: Current working conditions of physicians in hospitals display characteristics, which on the long term are harmful for the physicians mental and physical health (distress). There are problems concerning the work flow and the organization of working time which finally leads to gratification crises. How physicians perceive their stress-related working conditions is the issue this study wants to investigate. METHODS: In this study 12 062 physicians in hospitals were invited to an anonymized online-survey. 2064 physicians took part. The basis of this investigation is built by 2 theoretical stress models: The effort-reward imbalance models of Siegrist and the job-demand-control model of Karasek. Through these theoretical models distress is measured. RESULTS: The study revealed a high prevalence (55,5 %) of distress among physicians in hospitals. Furthermore there were significant differences between gender (59,7 % of female and 51,5 % of male physicians; OR 1,40; 95 %-CI 1,17-1,66; p < 0,001), between age (61,9 % of under 35-year-old and 49,4 % of over 59-year-old; OR 1,67; 95 %-CI 1,06-2,62; p < 0,001) and between the functional position (24,6 % of chief physician and 63,8 % of junior doctors; OR 5,40; 95 %-CI 3,03-9,65; p < 0,001). An additional analysis of the psychosocial aspects of the working conditions showed that these aspects are rated positively by this sample. CONSEQUENCES: These results have to be considered as a cause for concern, because this high prevalence of distress will lead sooner or later to a migration of qualified physicians abroad or to other (less stressful) jobs. In order to prevent a future shortage of qualified physicians, the working conditions have to be adapted to current needs and expectations of the younger generation. PMID- 24221975 TI - [Orthotopic liver transplantation for polycystic liver disease with massive hepatomegaly]. AB - HISTORY: A 51-year-old man (126 kg, 192 cm) with massive hepatomegaly causing cardiopulmonary symptoms was referred to our transplant center 14 years after initial diagnosis of polycystic liver disease. TREATMENT AND COURSE: Uneventful hepatectomy was followed by orthotopic liver transplantation using caval replacement. Donor liver came from a 73-year-old woman (extended criteria donor organ offer). A portocaval shunting was not established during transplantation although the explanted liver weighed 22 kg. 18 months after transplantation liver function is stable and the patient enjoys normal quality of life. CONCLUSION: This case report demonstrates the value and success of transplantation for patients suffering from enormous hepatomegaly due to polycystic liver disease. PMID- 24221976 TI - [Rare cause for severe hypertriglyceridemia - case 9/2013]. AB - HISTORY AND ADMISSION FINDINGS: We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. INVESTIGATIONS: Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. DIAGNOSIS, TREATMENT AND COURSE: Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. CONCLUSIONS: Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment. PMID- 24221977 TI - [76-year-old woman with dyspnea and cardiac decompensation]. PMID- 24221978 TI - [A current view to the diagnostic and therapeutic options of venous thromboembolism]. AB - The acute venous thromboembolism (VTE) is a life threatening event which might cause difficulties in diagnostic and therapeutic considerations because of the nonspecific symptomatic. In addition to the probability of a VTE, the risk stratification is of decisive importance to the further diagnostic and therapeutic management. The introduction of the new oral direct anticoagulation substances offer important variation to the previous therapy options and are mentioned in this article. The duration of the secondary prophylaxis therapy of VTE will be much more influenced by the reduced bleeding risk profile of the new agents. PMID- 24221979 TI - [Nosocomial measles infections]. AB - Measles is re-emerging in several developed countries because of suboptimal vaccination coverage. Health-care facilities play a crucial role in the transmission of measles infection. Nosocomial measles may contribute for an important part of cases in measles epidemics, especially in countries where measles is largely under control. The risk of acquiring measles is estimated to be 2 to 19 times higher for susceptible healthcare personnel (HCP) than for the general population. Measles vaccination of HCP should be included by all health care facilities as part of a strict occupational health program. All HCP should have documented evidence of measles immunity. Immunity against measles should be a prerequisite for working in areas where the most vulnerable patients are cared for. Both occupational and public health measures are needed to ensure that nosocomial measles should be comprehensively monitored and consistently prevented. PMID- 24221980 TI - [Medical practice for the purpose of pension insurance]. PMID- 24221981 TI - Seasonal cycle and regulation by temperature of antifreeze protein mRNA in a Long Island population of winter flounder. AB - The seasonal cycle and regulation by temperature of antifreeze protein mRNA (AF mRNA) were investigated in a Long Island population of winter flounder (Pseudopleuronectes americanus) by Northern blot hybridization and by in vitro translation of liver RNA. AF mRNA was expressed at high levels in the fall and winter (Nov.-Feb.) and at low or undetectable levels in the summer. The time of accumulation of AF mRNA coincides with the time during which water temperature and photoperiod decrease to 4 degrees C and 9 h of light per day, respectively. A temperature and photoperiod decrease in the laboratory during this time also resulted in high levels of AF mRNA. The levels of other mRNAs, as assayed by in vitro translation, were relatively constant during both seasonal acclimation and laboratory acclimation. The seasonal cycle of AF mRNA in Long Island winter flounder is similar to that of a more northern, Newfoundland population of winter flounder and different from that of an intermediate, New Brunswick population. These similarities and dissimilarities are discussed in light of potentially different exogenous and endogenous regulatory cues in the different populations. PMID- 24221982 TI - Dynamic characteristics of serotonin and dopamine metabolism in the rainbow trout brain: a regional study using liquid chromatography with electrochemical detection. AB - Aminergic metabolism was studied in discrete brain regions of the postovulated female rainbow trout using a liquid chromatography electrochemical detection method. 3 Methoxytyramine (3MT) was the major dopaminergic catabolite, suggesting that catechol-o-methyl transferase is the main dopamine (DA) catabolic enzyme. Two populations of brain regions were found: one with a high DA content and low 3MT/DA ratio (hypothalamus and telencephalon), suggesting that these regions could present a high density of DA perikarya; the other with a high 3MT/DA ratio (pituitary, preoptic area, myelencephalon and optic tectum) suggesting that these regions could present a high density of DA axonal endings. 5 Hydroxytryptamine (5HT) content differed, but an homogeneous distribution of monoamine oxidase was found in different brain regions. High 5HT content was found in the hypothalamus and telencephalon; 5HT was however not detectable in the pituitary. PMID- 24221983 TI - Induction and duration of tonic immobility in the lemon shark, Negaprion brevirostris. AB - Tonic immobility (TI) is an unlearned behavioral response characterized by a state of immobility and torpor. Effect of inter-trial interval on duration of tonic immobility was assessed in thirty, juvenile lemon sharks (Negaprion brevirostris). Regression analyses showed that massed trials of 12 per session increased the average duration of tonic immobility by 475 sec compared to spaced trials of 1 per session. Each experiment was composed of 24 trials. TI is stable and durations much longer in the lemon shark than for other sharks. These findings have enabled us to develop a quantitative bioassay for use in testing chemical shark repellents. PMID- 24221984 TI - The dynamics of vitellogenin sequestration into vitellogenic ovarian follicles of the rainbow trout, Salmo gairdneri. AB - This study provides quantitative data on the dynamics of protein sequestration into vitellogenic follicles of the rainbow trout, Salmo gairdneri. The ovarian uptake of both radiolabelled vitellogenin (VTG) and bovine serum albumin (BSA) were investigated in a homogenous population of maturing vitellogenic females.Ten fish were injected with (3)H. VTG directly into the bloodstream. Concomitantly, five of these fish received an equal amount of (14)C.BSA. Twenty two hours after injection, of the tissues sampled, the greatest proportions of (3)H. VTG were present in the blood (into which the radio labels were administered) and in the ovary (up to 28% and 46% of that originally present in the blood, respectively). VTG uptake was both selective, rates of uptake far exceeding that of the (14)C.BSA, and rapid. (3)H. VTG was sequestered at rates of between 35 to 390 ng.mm(2) follicle surface(-1).h(-1) in the different fish. The rates of VTG uptake into similarly sized follicles varied both between different sites within the ovary (by up to 30%) and also between the ovaries (by up to 38%) of an individual fish. PMID- 24221985 TI - Can the mudskipper, Periophthalmus chrysospilos, tolerate acute environmental hypoxic exposure? AB - The mudskipper P. chrysospilos became inert at 0.76 MUl O2.ml(-1) when it was allowed to respire in a 'closed respiratory chamber'. No ethanol was detected although it excreted three times more total carbon dioxide into the surrounding sea water than the amount of oxygen consumed. However, P. chrysospilos could survive environmental hypoxic exposure (0.8 MUl O2.ml(-1)) for at least 6 h. Upon normoxic recovery, the oxygen debt repayment was only a small fraction of the oxygen deficit incurred during the 6 h of hypoxic exposure. It would therefore appear that P. chrysospilos was able to cope with environmental hypoxia by suppressing its metabolic rate. PMID- 24221986 TI - Endocytosis via the scavenger- and the mannose-receptor in rainbow trout (Salmo gairdneri) pronephros is carried out by nonphagocytic cells. AB - Endocytosis of modified human serum albumin (HSA) and mannose-terminated glycoproteins was studied in pronephros cells from rainbow trout (Salmo gairdneri). Blood clearance and tissue uptake of dinitrophenylated human serum albumin (DNP-HSA) was dependent on the number of DNP-groups conjugated to the albumin molecule. Uptake of DNP35-HSA in isolated pronephros cells was saturable. Pronephros cells also internalized the mannose-terminated glycoprotein invertase by a receptor-mediated process. DNP-HSA and invertase were recovered in the same cell fractions when pronephros cells containing in vivo endocytosed ligands were separated by density gradient centrifugation. The cells endocytosing these ligands were apparently not macrophages. The macrophages were recovered in cell fractions with higher densities. They were identified by their ability to adhere to glass and to carry out phagocytosis. Cultured macrophages did not endocytose chemically modified albumin (DNP-HSA and formaldehyde-treated albumin) and mannose-terminated glycoproteins (ovalbumin) in vitro. These ligands were not recovered in glass adherent pronephros cells after in vivo endocytosis of the proteins. The present data suggest that macrophages in rainbow trout pronephros possess neither the receptor for chemically modified albumin, the scavenger receptor, nor the mannose-specific receptor. PMID- 24221987 TI - Incorporation and metabolism of (n-3) and (n-6) polyunsaturated fatty acids in phospholipid classes in cultured rainbow trout (Salmo gairdneri) cells. AB - The incorporation and metabolism of various (n-3) and (n-6) polyunsaturated fatty acids supplemented to the culture medium was investigated in the rainbow trout cell line, RTG-2. The distribution, and the occurrence and relative extent of further desaturation and elongation of the incorporated acids was determined in individual phospholipid classes by analysis of the fatty acid compositions. RTG-2 cells exhibited Delta6 and Delta5 desaturase activities whereas Delta4 desaturase activity was almost totally absent. The percentage of precursor acids was greatest in the phosphatidic acid/cardiolipin fraction (PA/CL), suggesting a role for possibly PA in the initial incorporation of these acids into the phospholipid pool. The compositional data indicated that individual intermediates and products of the desaturation pathways were associated with specific phospholipid classes probably via mechanisms depending upon the specificities of the acylating enzymes. The composition of phosphatidylinositol (PI) and the tightly controlled mechanisms for generating/maintaining it are consistent with a role for this phospholipid in providing precursor fatty acid for eicosanoid synthesis. PMID- 24221988 TI - Incorporation and metabolism of (n-3) and (n-6) polyunsaturated fatty acids in phospholipid classes in cultured turbot (Scophthalmus maximus) cells. AB - The incorporation and metabolism of various (n-3) and (n-6) polyunsaturated fatty acids (PUFA) supplemented to the culture medium was investigated in a turbot cell line (TF). The distribution, and the occurrence and extent of further metabolism of incorporated PUFA via desaturation/elongation mechanisms in specific phospholipid classes was determined from the different fatty acid compositions. The cells contained Delta6 and Delta4 desaturase activities but were generally deficient in C18-20 elongase activity. Delta5 Desaturase activity was generally masked by this deficiency but was present. The compositional data indicated that there was a high degree of specificity between individual phospholipid classes and particular fatty acids probably driven by the specificities of the acylating enzymes. The highest percentages of the supplemented acids were generally observed in the phosphatidic acid/cardiolipin fraction (PA/CL), suggesting a role for PA in the incorporation of the supplemented acids into the phospholipid pool. PI had a characteristic composition consistent with a putative role as a pool of precursor fatty acid for eicosanoid synthesis. Mechanisms were evident for generating and/or maintaining this composition. PMID- 24221989 TI - The conversion of linoleic acid and linolenic acid to longer chain polyunsaturated fatty acids by Tilapia (Oreochromis) nilotica in vivo. AB - Tilapia (Oreochromis) nilotica were fed either a commercial diet containing 2.2% (n-3) and 0.5% (n-6) polyunsaturated fatty acids (PUFA), or a diet containing 1.0% methyl linoleate as the only PUFA. The fatty acid composition of tissue lipids generally reflected that of the diet. Fish from both dietary groups were injected intraperitoneally with (14)C-labelled linoleic acid, 18:2 (n-6), or linolenic acid, 18:3 (n-3), and the distribution of radioactivity in tissue lipids examined. The conversion of both 18:2 (n-6) and 18:3 (n-3) to longer chain PUFA was lower in fish fed the commercial diet than in those fed the diet containing only 18:2 (n-6). Half of the radioactivity from both substrates recovered in liver polar lipids was present in C20 and C22 PUFA with fish maintained on the experimental diet. It is concluded that T. nilotica is capable of elongating and desaturating both 18:2 (n-6) and 18:3 (n-3), but that this conversion is suppressed by dietary longer chain PUFA. PMID- 24221990 TI - Alsobacter metallidurans gen. nov., sp. nov., a thallium-tolerant soil bacterium in the order Rhizobiales. AB - A thallium-tolerant, aerobic bacterium, designated strain SK200a-9(T), isolated from a garden soil sample was characterized using a polyphasic approach. Comparative analysis of 16S rRNA gene sequences revealed that strain SK200a-9(T) was affiliated with an uncultivated lineage within the Alphaproteobacteria and the nearest cultivated neighbours were bacteria in genera in the family Methylocystaceae (93.3-94.4% 16S rRNA gene sequence similarity) and the family Beijerinckiaceae (92.3-93.1%) in the order Rhizobiales. Cells of strain SK200a 9(T) were Gram-stain-negative, non-motile, non-spore-forming, poly-beta hydroxybutyrate-accumulating rods. The strain was a chemo-organotrophic bacterium, which was incapable of growth on C1 substrates. Catalase and oxidase were positive. Atmospheric nitrogen fixation and nitrate reduction were negative. The strain contained ubiquinone Q-10 and cellular fatty acids C18 : 1omega7c, C18 : 0, C16 : 1omega7c and C16 : 0 as predominant components. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content was 64.8 mol%. On the basis of the information described above, strain SK200a-9(T) is considered to represent a novel species of a new genus in the order Rhizobiales, for which the name Alsobacter metallidurans gen. nov., sp. nov. is proposed. The type strain of Alsobacter metallidurans is SK200a-9(T) ( = NBRC 107718(T) = CGMCC 1.12214(T)). PMID- 24221991 TI - Serological survey and risk factors for brucellosis in water buffaloes in the state of Para, Brazil. AB - To evaluate the prevalence and possible risk factors for brucellosis caused by Brucella abortus in water buffaloes in the state of Para, Brazil, 3,917 female buffalo serum samples from pregnant and non-pregnant animals were examined: 2,809 from Marajo Island and 1,108 from the mainland. The buffered acidified plate antigen (BAPA) screening test positively diagnosed 4.8% (188/3,917) of the animals with brucellosis, and the 2-mercaptoethanol (2-ME) confirmatory test affirmed 95.7% (180/188) of the results. The brucellosis prevalence was 4.17 times greater in mainland animals than on Marajo Island, with the highest prevalence in Tailandia (11.30%) and Paragominas (12.38%). Brucellosis seroprevalence was significantly influenced (p < 0.05) by reproductive status, with pregnant females being most vulnerable. These results demonstrate that brucellosis infection is active in the Brazilian region containing the largest buffalo population and that this disease poses a threat to public health and buffalo production in Para. PMID- 24221992 TI - New approach to quantification of molecularly targeted radiotracer uptake from hybrid cardiac SPECT/CT: methodology and validation. AB - Quantification of molecularly targeted radiotracer uptake in the myocardium from SPECT remains challenging in part due to potentially low levels of focal tracer uptake of presently available molecularly targeted agents and further degradation of cardiac SPECT by extracardiac radioactivity and partial-volume effect. The purpose of this study was to derive and validate a new SPECT quantification method for assessments of absolute radiotracer uptake in the myocardium. METHODS: The method was integrated with a hybrid micro-SPECT/CT imaging protocol to calculate radiotracer uptake of a molecularly targeted agent in the ischemic myocardium. CT coregistered with SPECT was used to identify the position and orientation of the left ventricle. Corrections for extracardiac activity and partial-volume errors were performed via a heuristic method derived with a total count sampling scheme. Myocardial radiotracer uptake was quantified from SPECT using an external point source as a known reference. Methods were validated using an ischemic rat model injected with a (99m)Tc-labeled SPECT radiotracer targeted at alphavbeta3 integrin. SPECT-quantified myocardial radiotracer uptake was compared with postmortem myocardial tissue well-counted radioactivity. RESULTS: Initial correlation between SPECT-quantified and well-counted radioactivity was fair (R(2) = 0.19, y = 0.50x + 0.05, P = 0.06) when no correction was applied to SPECT quantification. Correlation was significantly improved with tissue weight correction (R(2) = 0.84, y = 1.82x - 0.01, P < 0.001), and a trend toward the improvement of correlation was observed with extracardiac activity correction (R(2) = 0.85, y = 1.54x - 0.01, P < 0.001) and partial-volume correction (R(2) = 0.86, y = 1.68x - 0.01, P < 0.001). Reproducibility of the SPECT quantification was excellent, either with no correction (R(2) = 0.99, y = 1.00x + 0.00, P < 0.001) or with all corrections (R(2) = 1.00, y = 1.00x - 0.00, P < 0.001). CONCLUSION: Corrections for the myocardial tissue weight, extracardiac activity, and partial-volume errors are crucial for precise assessments of myocardial radiotracer uptake using micro-SPECT/CT. The quantitative SPECT/CT approach developed provides a reasonable and reproducible in vivo estimation of absolute radiotracer uptake in a model of myocardial injury and should permit quantitative serial monitoring of subtle changes in the myocardial uptake of targeted radiotracers. PMID- 24221993 TI - Resveratrol suppresses cancer cell glucose uptake by targeting reactive oxygen species-mediated hypoxia-inducible factor-1alpha activation. AB - Resveratrol is gaining attention for its anticancer effects and is also recognized for its antioxidant properties and influence on glucose metabolism. Augmented reactive oxygen species (ROS) and high glycolytic flux are common characteristics of malignant cells. We thus evaluated the effect of resveratrol on cancer cell glucose metabolism and investigated the role of ROS in the response. METHODS: Cancer cells were measured for cell content and (18)F-FDG uptake. Assays were performed for lactate production; hexokinase activity and intracellular ROS; and immunoblotting for hypoxia-inducible factor-1alpha (HIF 1alpha), Akt, mammalian target of rapamycin, and glucose transporter type 1 (Glut 1). Animal studies were performed with small-animal PET imaging of Lewis lung carcinoma tumor-bearing mice. RESULTS: Resveratrol mildly decreased cell content and more pronouncedly suppressed (18)F-FDG uptake in Lewis lung carcinoma, HT-29 colon, and T47D breast cancer cells. Hence, (18)F-FDG uptake normalized to cell content was reduced to less than half of controls by 24-h exposure to resveratrol. This reduction was attributed to reduced glycolytic flux and Glut-1 expression. Resveratrol also decreased intracellular ROS in patterns that closely paralleled (18)F-FDG uptake. Scavenging of ROS with N-acetyl cysteine, but not inhibition of nicotinamide adenine dinucleotide phosphate oxidase, was sufficient to suppress (18)F-FDG uptake. Conversely, ROS inducers effectively reversed the metabolic response of resveratrol. HIF-1alpha protein was markedly reduced by resveratrol, and inhibiting HIF-1alpha expression with cycloheximide or specific small interfering RNAs suppressed (18)F-FDG uptake. The proteosomal inhibitor MG132 partly restored HIF-1alpha level and (18)F-FDG uptake in resveratrol treated cells. Resveratrol also inhibited Akt activation; in addition, inhibitors and small interfering RNAs against phosphoinositide 3-kinase decreased (18)F-FDG uptake. Finally, small-animal PET results showed resveratrol treatment to suppress tumor (18)F-FDG uptake in vivo. CONCLUSION: Resveratrol suppresses cancer cell (18)F-FDG uptake and glycolytic metabolism in a manner that depends on the capacity of resveratrol to inhibit intracellular ROS, which downregulates HIF-1alpha accumulation. PMID- 24221995 TI - Study on the pretreatment of poly(ether ether ketone)/multiwalled carbon nanotubes composites through environmentally friendly chemical etching and electrical properties of the chemically metallized composites. AB - The high-volume resistivity and surface resistance of poly(ether ether ketone)/multiwalled carbon nanotubes (PEEK/MWCNT) composites restrict their use in an electronic field. To decrease the volume resistivity and surface resistance, we metalized the composites by electroless plating. The composites and metal coatings were characterized by SEM, XPS, AFM, EDX, and XRD spectroscopy. The swelling ratio of the composites, volume resistivity of two side-coated composites, sheet resistance of plated composites, and adhesion between the coating and PEEK/MWCNT were tested. The results are as follows. A high roughness and a small swelling ratio were obtained by swelling in 18 mol/L H2SO4 for 3 min. Most of the MWCNT on the surface were still wrapped with PEEK after swelling. To expose the MWCNT, an environmentally friendly and effective etchant (MnO2-NaH2PO4-H2SO4) was used. After etching, not only were high roughness and partially exposed MWCNT obtained but also the percentage of hydrophilic groups on the surface was increased. A dense cauliflower-like Ni-P coating was produced, and the exposed MWCNT were embedded in the metal coating after electroless plating for 20 min. The coating exhibited an amorphous structure with a phosphorus content of 11.21 wt %. The volume resistivity of two side-coated PEEK/MWCNT dropped sharply to 38 Omega.m after electroless plating for 5 min. The sheet resistance decreased with increasing the electroless-plating time, and it dropped to 0.88 Omega/square after electroless plating for 40 min. The adhesion of the coating reached the highest 5 B scale (ASTM D3359) and could even undergo the test 20 times. PMID- 24221994 TI - Intended versus inferred care after PET performed for initial staging in the National Oncologic PET Registry. AB - The National Oncologic PET Registry (NOPR) collected data on intended management before and after PET in cancer patients. We have previously reported that PET was associated with a change in intended management of about one third of patients and was consistent across cancer types. It is uncertain if intended management plans reflect the actual care these patients received. One approach to assess actual care received is using administrative claims to categorize the type and timing of clinical services. METHODS: NOPR data from 2006 to 2008 were linked to Medicare claims for consenting patients aged 65 y or older undergoing initial staging PET scanning for bladder, ovarian, pancreatic, small cell lung, or stomach cancers. We determined the 60-d agreement between claims-inferred care and NOPR treatment plans. RESULTS: Patients (n = 4,661) were assessed, and 30% 52% had metastatic disease. Planned treatments were about two-thirds monotherapy, of which 46% was systemic therapy only, and one-third combinations. Claims paid by 60 d confirmed the NOPR plan of any systemic therapy, radiotherapy, or surgery in 79.3%, 64.7%, and 63.6%, respectively. Single-mode plans were much more often confirmed: systemic therapy in more than 85% of patients with ovarian, pancreatic, and small cell lung cancers and surgery in more than 73% of those with bladder, pancreatic, and stomach cancers. Intended combination treatments had claims for both in only 28% of patients receiving surgery-based combinations and in 55% receiving chemoradiotherapy. About 90% of patients with NOPR-planned systemic therapy had evaluation or management claims from a medical oncologist. An age of less than 75 y was associated more often with confirmation of chemotherapy, less often for radiotherapy but not with confirmation of surgery. Performance status or comorbidity did not explain confirmation rates within action categories, but confirmation rates were higher if the referrer specialized in the planned treatment. CONCLUSION: Claims confirmations of NOPR intent for initial staging were widely variable but were higher than previously reported for restaging PET, suggesting that measuring change in intended management is a reasonable method for assessing the impact diagnostic tests have on actual care. PMID- 24221996 TI - Reactions of proton-bound dimers. AB - Thermal reactions of proton-bound dimers, (CH3CN)2H (+), (CH3OCH3)2H (+), and (CH3COCH3)2H(+), were studied using a selected ion flow tube. Reactions observed include association, switching, and proton transfer. The association channel was observed only for base molecules that had hydrogen bonding protons such as NH3, CH3NH2, (CH3)2NH, and CH3OH. An association-insertion mechaniSoc was proposed in which the central proton of the symmetrically bound dimers is replaced by a protonated base, for example, NH 4 (+) . These reactions are relatively slow, which demonstrates a central barrier along the potential energy surface. Ether containing dimers do not demonstrate this insertion reaction, except for diethers, for example, CH3OCH2CH2OCH3, which can form stable bicyclic structures. Dimers such as (HCOOH)2H(+), which possess hydrogen bonding protons in the periphery, undergo switching reactions with ammonia and no insertion. PMID- 24221997 TI - The effect of protonation site on bond strengths in simple peptides: Application of Ab initio and modified neglect of differential overlap bond orders and modified neglect of differential overlap energy partitioning. AB - A comparative study of ab initio 6-31G(*) and semiempirical modified neglect of differential overlap (MNDO) bond orders and MNDO diatomic energy contributions for the description of bond strengths in neutral and protonated glycine, diglycine, triglycine, and dialanine is presented. Good correlations were found between 6-31G(*) and MNDO bond orders and between MNDO bond orders and diatomic energy contributions. Although bond orders and diatomic energy contributions are inherently different quantities, both predict the changes in bond strengths due to protonation to be qualitatively the same. The theoretically predicted differences in bond strengths for different protonated forms clearly indicate that in peptide fragmentation schemes one should consider even those protonated forms whose formation is not preferred energetically. PMID- 24221998 TI - Gas-phase basicities of serine and dipeptides of serine and glycine. AB - The gas-phase basicities of serine and dipeptides containing amino acid residues of serine and glycine were determined by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer. The gas-phase basicity (GB) of L-serine was found to be 205.9 kcal/mol, with addition of a hydroxymethyl group (-CH2OH) increasing the basicity by 4.5 kcal/mol relative to the simplest amino acid glycine (GB = 201.4 kcal/mol). This is attributed to a combination of intramolecular hydrogen bonding, induction, and symmetry effects. For the dipeptides, addition of a hydroxymethyl group does not result in a large increase in basicity relative to the basicity of glycylglycine (GB = 208.0 kcal/mol). The gas-phase basicities determined for glycyl-L-serine, L-serylglycine, and L-sery-L serine are 209.3,210.6, and 210.9 kcal/mol, respectively. In comparison to glycylglycine, addition of the hydroxymethyl group at the N terminus has a greater impact on basicity than its placement at the C terminus. These data suggest that the protonation site for these dipeptides is the N-terminal amino nitrogen. PMID- 24221999 TI - Chirality in microcystins. AB - A new method has been developed to identify the isomers of amino acids by derivatization of the corresponding standards with 1-fluoro-2,4-dinitrophenyl-5-L alanine amide (Marfey's reagent or FDAA) and analysis of the diastereomeric derivatives by a liquid chromatography-thermospray mass spectrometry technique. Quantification of the FDAA derivatives that originate from standards was possible by using L-phenylalanine as the internal standard. The procedure was applied to determine the chiralities of the amino acids present in some previously uncharacterized blue-green algal peptides (microcystins). PMID- 24222000 TI - Analysis of hydrocarbon dendrimers by laser desorption time-of-flight and fourier transform mass spectrometry. AB - The first mass spectrometric analysis of a new class of hydrocarbon dendrimers that result from a convergent synthetic approach is reported. Molecular weights of a series of phenylacetylene dendrimers (715 to 14776 u MW) are characterized by ultraviolet matrix-assisted laser desorption (MALDltime-of-flight (TOF) mass spectrometry, direct and silver chemical ionization infrared laser desorption Fourier transform mass spectrometry @I'MSl, and ultraviolet matrix-assisted laser desorption silver chemical ionization Fourier transform mass spectromeby. New matrices and techniques were developed to facilitate analysis of the dendrimers. Mass measurement accuracies between 10 and 25 ppm are obtained for molecular ion species of the five dendrimers analyzed. Laser desorption time-of-flight and FI'MS techniques are shown to be complementary, with FTMS providing high mass resolution (27,000-67,000 resolving power) and accuracy for lower mass dendrimers (10-14 ppm) and MALD TOF yielding the highest resolution (1100 resolving power) and accuracy (25 ppm) for the largest dendrimer. These results are consistent with proposed empirical formulas. PMID- 24222001 TI - Ion trap tandem mass spectrometry applied to small multiply charged oligonucleotides with a modified base. AB - Two isomeric oligodeoxynucleotide hexamers, 5'-d(N-6meATGCAT)-3' and 5' d(ATGSmeCAT)-3', were subjected to analysis by electrospray and ion trap mass spectrometry. In the case of the isomer with a modified adenine, location of the modified base in the sequence was straightforward and a triple mass spectrometry experiment provided information on the identity of the modification. In contrast, the isomer with the methylated cytosine did not yield definitive information on the location or identity of the modification. Tandem mass spectrometry data in this case could indicate that the modification was present on either the third or fourth nucleoside. The two isomers represent extremes in the facility with which modified bases can be identified and located in a small oligonucleotide via multiple mass spectrometry of multiply charged anions. A preference for loss of particular bases strongly influences which structurally diagnostic ions are formed upon collisional activation. The likelihood for locating and identifying a modified base is dependent, therefore, upon the likelihood that the base is lost directly from the parention. PMID- 24222002 TI - Ion spray-tandem mass spectrometry of supramolecular coordination complexes. AB - Double-helical [M2L2] (n+), triple-helical [M2L3] (n+), and toroidal [M3L3] (n+) (M = Cu, Co, Fe, Ni, La, Eu, Gd, Tb, or Lu) supramolecular complexes have been fully characterized by ion spray mass spectrometry (IS-MS). The IS-MS spectra from pure acetonitrile solutions reflect the nature of the cations present in solution with conservation of the charge state and allow an efficient qualitative speciation of the compounds. The mass spectrometry results can be correlated with other powerful techniques (nuclear magnetic resonance and electronic spectroscopy) for the characterization of supramolecular complexes in solution, Structural information is obtained by collision-induced dissociation, which strongly depends on the metal ions used in the supramolecular complexes and on the various connectivities and topologies of the ligands. When the ligand contains 3,5dimethoxybenzyl groups bound to the benzimidazole rings, the partial fragmentation of the complexes is associated with a decrease of the total charge of the complexes and the appearance of the characteristic fragment at m/z 151 that corresponds to the 3,5-dimethoxybenzyl cation. A detailed analysis of the fragmentation pathways of these supramolecular complexes suggests that the metal nitrogen coordination bonds are very strong in the gas phase. PMID- 24222003 TI - Negative chemical ionization in quadrupole ion trap mass spectrometry: Effects of applied voltages and reaction times. AB - The effects of applied voltages and reaction times on negative ion chemical ionization in the quadrupole ion trap are investigated. Mass-selected ejection of undesired reagent ions and selective mass storage of only negative ions are required for practical negative ion chemical ionization. This is achieved by application of rf and dc voltages to the ring electrode to control the mass-to charge ratios one polarity) of ions stored, as well as by application of a supplemental rf voltage applied across the endcap electrodes to selectively eject ions of a particular mass-to-charge ratio. Even with careful control of these parameters, negative chemical ionization is not as sensitive as electron ionization and positive chemical ionization because of the lack of thermal electrons in the ion trap. Mass selection of the hydroxide anion as a reagent ion and exclusion of all positive ions provide [M - H](-) ions with little or no fragmentation for a wide variety of compounds. PMID- 24222004 TI - Implementation of the chemical reaction interface mass spectrometry technique on a Hewlett-Packard mass-selective detector. AB - A microwave-powered chemical reaction interface has been installed in a Hewlett Packard gas chromatograph-mass spectrometer (GC-MS) system (5890 IT gas chromatograph-S971 mass-selective detector). The technical details and optimization strategies are discussed. The evaluation of this new setup is presented, showing detection limits of 1 ng of (13)C-, (15)N-, and Cl-containing compounds with signal-to-noise ratios greater than or egual to 3. Selective detection was evaluated with a urine sample from a dog dosed with (15)N3 midazolam that had been previously analyzed by using a differentially pumped research-level quadrupole mass spectrometer. The results show that the detection of (15)N and Cl remains highly selective and the mass-selective detector gives comparable sensitivity to the larger instrument when the latter is operating over a conventional mass range. The capability for chemical reaction interface mass spectrometry can be easily accomplished with an inexpensive GC-MS system. PMID- 24222005 TI - Resolution limitations from detector pulse width and jitter in a linear orthogonal-acceleration time-of-flight mass spectrometer. AB - Recent and ongoing advances in timing electronics together with the development of ionization techniques suited to time-of-flight mass spectrometry (TOF-MS) have contributed to renewed interest in this method of mass analysis. Whereas low resolving powers (m/?m < 500) were once an almost unavoidable drawback in TOF-MS, recent developments in instrument geometries have produced much higher resolving powers for many ion sources. The temporal width of detector pulses and jitter in timing electronics, however, lead to contributions to peak widths that are essentially independent of the mass-analyzer ion optics. The effective detector pulse width (?t d ~ 1-10 ns typically) can be a limiting factor in the development of high resolution time-of-flight (TOF) instruments with modest drift lengths (~1 m), It also reduces the mass resolution more seriously for light ions. This article presents a method for distinguishing the instrumental "ion arrival-time" resolution (R o) of a linear TOF mass analyzer from that which is locally measured at a particular mass, limited by the broadening of the detector pulse width and electronics. The method also provides an estimate of ?t d, that is useful in determining the temporal performance of the detection system. The model developed here is tested with data from a recently constructed orthogonal acceleration TOF mass spectrometer equipped with a commercially available transient recorder (a LeCroy 400-Msamplejs digital oscilloscope) from which we obtained R o = 4240 +/- 100 [full width at half maximum (FWHM)) and ?t d = 3.0 +/ 0.1 ns (FWHM). PMID- 24222006 TI - Improved energy compensation for time-of-flight mass spectrometry. AB - A model for improved energy compensation in time-of-flight (TOF) mass spectrometry has been developed and tested. This model includes effects of both the acceleration and drift region on mass resolution for surface desorption TOP mass spectrometers that employ ion mirrors to improve mass resolution. Appropriate placement of an additional stage onto the conventional one- and two stage mirrors provides compensation for flight time spreads, caused by initial ion kinetic energy distributions, in both regions. Experimental results that validate the model calculations are presented for a modified commercial two-stage ion mirror. For example, m/?m for Na(+) was improved from ~ 100 to ~ 200 using only a 200-eV drift energy and a 58-cm drift path. PMID- 24222008 TI - Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix. AB - Although oxygen and extracellular matrix cues both influence differentiation state and metabolic function of primary rat and human hepatocytes, relatively little is known about how these factors together regulate behaviors of primary mouse hepatocytes in culture. To determine the effects of pericellular oxygen tension on hepatocellular function, we employed two methods of altering oxygen concentration in the local cellular microenvironment of cells cultured in the presence or absence of an extracellular matrix (Matrigel) supplement. By systematically altering medium depth and gas phase oxygen tension, we created multiple oxygen regimes (hypoxic, normoxic, and hyperoxic) and measured the local oxygen concentrations in the pericellular environment using custom-designed oxygen microprobes. From these measurements of oxygen concentrations, we derived values of oxygen consumption rates under a spectrum of environmental contexts, thus providing the first reported estimates of these values for primary mouse hepatocytes. Oxygen tension and matrix microenvironment were found to synergistically regulate hepatocellular survival and function as assessed using quantitative image analysis for cells stained with vital dyes, and assessment of secretion of albumin. Hepatocellular viability was affected only at strongly hypoxic conditions. Surprisingly, albumin secretion rates were greatest at a moderately supra-physiological oxygen concentration, and this effect was mitigated at still greater supra-physiological concentrations. Matrigel enhanced the effects of oxygen on retention of function. This study underscores the importance of carefully controlling cell density, medium depth, and gas phase oxygen, as the effects of these parameters on local pericellular oxygen tension and subsequent hepatocellular function are profound. PMID- 24222010 TI - Hunchback is required for abdominal identity suppression and germband growth in the parthenogenetic embryogenesis of the pea aphid, Acyrthosiphon pisum. AB - Aphid, a short germband insect, displays an embryogenesis different from that of long germband insect species. Furthermore, the development of its parthenogenetic and viviparous embryo is different from that of the embryo resulting from sexual reproduction. To better understand the genetic regulation of this type of embryogenesis, the functions of hunchback in asexual Acyrthosiphon pisum were investigated by parental RNAi. Microinjection of Aphb double-stranded RNA yielded several defective phenotypes. Quantitative real-time PCR analysis revealed that these defects resulted from reduction of Aphb mRNA level in injected aphids. All these results suggested that the hb gene in parthenogenetic and viviparous Acyrthosiphon pisum was involved in abdominal identity suppression and germband growth as its homologue does in sexual insects. PMID- 24222009 TI - Informed consent when prescribing medication: a randomized controlled trial. AB - OBJECTIVES/HYPOTHESIS: To determine patient recall of specific risks associated with medication prescription and whether or not handouts are an effective tool to augment the informed consent process. STUDY DESIGN: Double-blinded, randomized, controlled trial. METHODS: Informed consent for prednisone prescriptions was studied by comparing the effect of a verbal discussion (describing 10 specific adverse drug reactions) in conjunction with a handout going over same, to a verbal discussion alone. Blinded assessments occurred by telephone interview 2 to 4 weeks following the intervention. Outcomes assessed were the number of risks of prednisone that patients could list and the number of risks they recalled having discussed with their physician. Other demographic details were also collected. RESULTS: Twenty-five participants were randomly allocated to each group. Without prompting, the median number of risks spontaneously recalled by the handout group was not significantly different than the control group, and both groups had very low recall (two vs. one, P = .24). When provided a list of potential side effects, it was observed that the handout group recalled a higher median number of risks having been discussed with their physician compared to patients in the control group (eight vs. five, P = .003). The groups' demographics were otherwise identical. CONCLUSIONS: Patients in general did not remember discussing adverse prednisone risks with their physician even a short time after the discussion took place. Although the patient handout resulted in improved recall of risks following the prescription of prednisone, its importance in the informed medication consent process remains an open question. LEVEL OF EVIDENCE: 1b. PMID- 24222011 TI - Neuroenhancement among Swiss students--a comparison of users and non-users. AB - INTRODUCTION: This survey aims to contribute to the current discussion about neuroenhancement by comparing cognitive enhancer(s) (CE) users with CE non-users with a focus on their characteristics and attitudes. METHODS: An online survey was sent out to all undergraduate and graduate students of the University of Zurich who allow such e-mails (n=8642), accompanied by advertisement for the survey in lectures. 1765 students completed the survey, which was about healthy people's use of Ritalin, Adderall and/or Modasomil to increase concentration and/or alertness. A complementary paper-and-pencil survey (n=97 students, response rate: 95.1%) was also carried out in order to compare data. RESULTS: Non therapeutic CE users (6.2%) were more often male, considered religion to be of less importance and had more experience with drugs. CE had been taken for study purposes by 4.7% of all students. CE users had tried Ritalin most often, which about half of them received from friends and colleagues. The CE users had more reasons for and fewer concerns about taking CE than non-users. The most common reasons for both groups were "the effects of learning quicker" and "for finishing more work in less time". The most common concerns for both groups were "the worries about possible side effects" and "the goal of CE to achieve more", and "an unnatural interference of such products with our bodies" (CE-users) or "the gut feeling of not using such products" (CE non-users). DISCUSSION: The comparison of CE users with CE non-users reveals insights about their attitudes, which will add to the understanding of why students take or could imagine taking such products. PMID- 24222012 TI - Sexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs. AB - INTRODUCTION: Sexual dysfunction is a potential side effect of mood stabilizers and anxiolytic drugs: this article presents a critical review of the current literature. Although many studies have been published on sexual side effects of psychopharmacological treatment, only a minority relate to mood stabilizers and anxiolytic drugs. Most of these studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, many of the studies on sexual dysfunction associated with mood stabilizers and anxiolytic drugs are limited by other methodological flaws. While there is evidence to suggest that mood stabilizers, with some exceptions, negatively affect sexual functioning, there is still insufficient evidence to draw any clear conclusions about the effects of anxiolytic drugs on sexual function. There is some weak evidence to indicate that switching from enzyme-inducing to non-enzyme-inducing anticonvulsant drugs, could be clinically useful. Some researchers recommend that sexual dysfunction in patients taking antiepileptic drugs should in general be treated according to standard guidelines for the management of sexual dysfunction, since reliable data on special populations is not available. However, specific approaches may be useful, but cannot yet be recommended until further validating research has been conducted. We did not find evidence supporting the use of any specific treatment strategy for sexual dysfunction associated with anxiolytic treatment. METHODS: This study was conducted in 2013 using the paper and electronic resources of the library of the Azienda Provinciale per i Servizi Sanitari (APSS) in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793, or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "anxiolytic drugs", "mood stabilizers", "benzodiazepines", "psychotrophic drugs", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction". All resulting listed articles were reviewed. DISCUSSION: This review includes studies that investigated the relationship between mood stabilizer and anxiolytic drug treatment and sexual dysfunction. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs. PMID- 24222013 TI - Opioids and traffic safety--focus on buprenorphine. AB - BACKGROUND: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. The effects of opioids such as buprenorphine on cognitive functioning and driving ability are a matter of debate. OBJECTIVES: A comprehensive review of studies of the effects of buprenorphine on traffic safety is presented. RESULTS: A number of recent epidemiological and road surveys indicate that opioids have a moderate risk for causing accidents compared to other drugs of abuse, such as alcohol. A number of neuropsychological studies, a few of which were prospective and used a randomized control group, have used standardized test batteries to measure domains relevant for psychomotor functioning and driving ability. Single doses of buprenorphine have been shown to induce some impairment in healthy volunteers, but less than found in chronic users. Some non-randomized studies indicate somewhat better cognitive performance of patients on buprenorphine than of those on methadone but this finding has not been demonstrated in randomized controlled trials. CONCLUSIONS: Opioids as a class of drugs induce some impairment of driving ability, but less than other psychotropic agents or drugs of abuse. Personality features such as impulsivity, sensation seeking, low risk perception and antisocial behaviour, comorbid psychiatric and neurological disorders and additional substance use of opioid users are of relevance for traffic safety. Buprenorphine does not cause more cognitive impairment than methadone or may even cause less. Caution is required when initiating treatment with buprenorphine. The risk for driving ability impairment is probably less under steady state conditions. Finally, higher doses of buprenorphine are probably not associated with more impairment. PMID- 24222014 TI - Mycophenolic acid-treated dendritic cells generate regulatory CD4+ T cells that suppress CD8+ T cells' allocytotoxicity. AB - Regulatory T cells (Treg) play a crucial role in controlling immunity and transplant rejection. Two main groups of Treg have been described: antigen induced Treg (iTreg) and natural Treg (nTreg). The ways to induce and the mechanisms of action of Treg subsets remained ill defined, particularly for their effects on CD8(+) T cells. CD8(+) T cells are major agents in the rejection of allografts; the aim of this study is to investigate the effects exerted on CD8(+) T cells by human CD4(+) iTreg induced by mycophenolic acid-treated dendritic cells. iTreg suppress the proliferation of CD8(+) T cells by allogeneic cell-cell interaction with mature dendritic cells and irrespectively of the TCR specificity of the CD8(+) T cells and cell-cell contact of iTreg with CD8(+) T cells. In our model, this suppression is independent of the action of IL-10 and TGF-beta1. iTreg were able to modify phenotype and inhibited IFN-gamma and TNF-alpha secretion by CD8(+) T cells. Most interestingly, iTreg inhibit the synthesis of perforin and of granzymes A and B by CD8(+) T cells and impaired their cytotoxicity against allogeneic targets. In summary, our study showed the involvement of iTreg in the down-regulation of cytotoxic responses mediated by CD8(+) T cells in an allospecific context. Following studies that have shown the existence of a regulation control exerted by iTreg on CD4(+) T cells and dendritic cells, this work ultimately shows that this regulation can reach CD8(+) T-cell functions. PMID- 24222015 TI - 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24222016 TI - 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24222020 TI - An interdisciplinary, biosocial perspective on human nature. PMID- 24222018 TI - 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24222019 TI - Apparent diffusion coefficient reproducibility of the pancreas measured at different MR scanners using diffusion-weighted imaging. AB - PURPOSE: To evaluate the reproducibility of the pancreatic apparent diffusion coefficient (ADC) measured at different MR scanners. MATERIALS AND METHODS: Twenty-four healthy volunteers underwent three consecutive diffusion-weighted imaging (DWI) at a GE 1.5 Tesla (T), a Siemens 1.5 T and a Philips 3.0 T (session 1), and imaged again using the same protocol at the same GE 1.5 T (session 2) 12 days later. The ADC values of pancreas were measured at all three MR scanners. Paired-sample t-test and the Bland-Altman method were used for ADC data analysis. RESULTS: The individual mean ADC values of pancreatic head, body, and tail (in 10(-3) mm(2)/s) measured at GE 1.5 T (2.24, 2.01, 1.88 for observer 1 and 2.23, 2.00, 1.92 for observer 2) and Siemens 1.5 T (2.24, 2.04, 1.84 for observer 1 and 2.20, 1.98, 1.84 for observer 2) were significantly higher than those at Philips 3.0 T (2.06, 1.80, 1.56 for observer 1 and 2.02, 1.79, 1.60 for observer 2) (P = 0.000-0.008). There was no significant difference of ADC values either between GE 1.5 T and Siemens 1.5 T (P = 0.115-0.966), or between imaging session 1 and 2 at GE 1.5 T (P = 0.072-0.938). The range of mean difference +/- limits of agreement (in 10(-3) mm(2)/s) was -0.07-0.04 +/- 0.39-0.53 between two 1.5 T scanners, and 0.04-0.04 +/- 0.24-0.47 between two imaging sessions at GE 1.5 T. CONCLUSION: The measured ADC values of pancreas are affected by the field strength of scanner, but show good reproducibility between different MR systems with same field strength and at the same MR system over time. PMID- 24222021 TI - Infertility, abortion, and biotechnology : When it's not nice to fool mother nature. AB - Patterns of reproductive failure described in humans and other mammals suggest that reproductive failure may in many instances be the result of adaptations evolved to suppress reproduction under temporarily harsh conditions. By suppressing reproduction under such conditions, females are able to conserve their time and energy for reproductive opportunities in which reproduction is most likely to succeed. Such adaptations have been particularly important for female mammals, given (a) the amount of time and energy that reproduction requires, and (b) the degree to which reproductive conditions can vary.The existence of conscious and unconscious mechanisms to suppress reproduction under poor conditions has several implications for obstetric/gynecologic practices. Two implications are discussed with reference to biotechnological advancements in our ability to facilitate conceptions and manage problem pregnancies: (a) potential dangers of sophisticated technologies overriding natural fertility controls; and (b) the need for greater appreciation of the association between psychosocial stress and reproductive failure in the treatment of reproductive problems. Implications for elective abortion practices are discussed as well. PMID- 24222017 TI - 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. PMID- 24222022 TI - Human adoption in evolutionary perspective. AB - Exploitation is a fundamental element of the parental strategies of many species of birds. Cuckoos, for example, lay their eggs in the nest of other birds, who often unwittingly rear the alien nestlings as their own. Nest parasitism is an efficient reproductive strategy for cuckoos, who do not have to worry about building a nest, incubating their eggs, or feeding their nestlings. But not all hosts respond passively to such intrusions. In response to parasitic cowbirds, for example, robins have evolved the ability to detect and selectively eject alien young from their nests. Human parenting strategies differ sharply from the strategies of cuckoos and robins. Unlike cuckoos, we are reluctant to allow our children to be raised by others. Unlike robins, we knowingly rear strange young. What makes human behavior toward children so different from that of cuckoos and robins? Humans seem to share a number of predispositions that facilitate successful adoptive relationships, and the desire to raise children seems to be pervasive among modern humans. Despite these commonalities, patterns of adoption transactions vary greatly among contemporary human societies. This paper considers the origins and causes of cross-cultural variation in human adoptive behavior from an evolutionary perspective. PMID- 24222024 TI - Killing the competition : Female/female and male/male homicide. AB - Sex- and age-specific rates of killing unrelated persons of one's own sex were computed for Canada (1974-1983), England/Wales (1977-1986), Chicago (1965-1981), and Detroit (1972) from census information and data archives of all homicides known to police. Patterns in relation to sex and age were virtually identical among the four samples, although the rates varied enormously (from 3.7 per million citizens per annum in England/Wales to 216.3 in Detroit). Men's marital status was related to the probability of committing a same-sex, nonrelative homicide, but age effects remained conspicuous when married and unmarried men were distinguished.These findings and the treatment of age and sex effects by criminologists are discussed in the light of contemporary evolutionary psychological models of sex differences and life-span development. Same-sex homicides in which killer and victim are unrelated can be interpreted as an assay of competitive conflict. In every human society for which relevant information exists, men kill one another vastly more often than do women. Lethal interpersonal competition is especially prevalent among young men, which accords with many other aspects of life-span development in suggesting that sexual selection has maximized male competitive prowess and inclination in young adulthood. PMID- 24222023 TI - Dietary and prophylactic iron supplements : Helpful or harmful? AB - Mild hypoferremia represents an aspect of the ability of the body to withhold iron from pathogenic bacteria, fungi, and protozoa, and from neoplastic cells. However, our iron-withholding defense system can be thwarted by practices that enhance iron overload such as indiscriminate iron fortification of foods, medically prescribed iron supplements, alcohol ingestion, and cigarette smoking. Elevated standards for normal levels of iron can be misleading and even dangerous for individuals faced with medical insults such as chronic infection, neoplasia, cardiomyopathy, and arthritis. We are becoming increasingly aware that the wide spread hypoferremia in human populations is a physiological response to insult rather than a pathological cause of insult, and that attempts to correct the condition by simply raising iron levels may not only be misguided but may actually impair host defense. PMID- 24222026 TI - A heated electrospray source for mass spectrometry of analytes from aqueous solutions. AB - An electrospray interface is described that provides high sensitivity and signal stability for mass spectrometric detection of analytes in solvents with high water content including 100% water. The electrospray capillary tip section is heated close to the boiling point of the solvent. An approximately 20 degrees C hotter airstream, with flow coaxial to the electrospray tip and codirectional to the electrospray.. is also used. With this arrangement, the analyte signal sensitivity and stability obtained with neat water is equal to that obtained with neat methanol. The heated electrospray also affords the use of a wide range of flow rates: 1-100 MUL/min. PMID- 24222025 TI - Enzymatic "click" ligation: selective cysteine modification in polypeptides enabled by promiscuous glutathione S-transferase. PMID- 24222027 TI - Effects of heavy-atom substituents on matrices used for matrix-assisted laser desorption-Ionization mass spectrometry. AB - The data reported show that heavy-atom substitution on matrices that are used for matrix-assisted laser desorption-ionization mass spectrometry enhance [M + H](+) ion yields of both Leu-enkephalin and vitamin B12. Heavy-atom substitution alters the excited state relaxation dynamics of the matrices as indicated by measured decreases in the measured luminescence (fluorescence and/or phosphorescence) observed for heavy atoms that contain matrices relative to the nonheavy-atom substituted matrices. The results presented are consistent with the direct involvement of an electronically excited state of the matrix in the formation of analyte [M + H](+) ions. PMID- 24222028 TI - Simulated ion trajectory and induced signal in ion cyclotron resonance ion traps. Effect of ion initial axial position on ion coherence, induced signal, and radial or z ejection in a cubic trap. AB - The effects of ion initial axial position on coherence of ion motion, induced ion cyclotron resonance (ICR) signal. and radial and z ejection have been evaluated by numerical simulation for a cubic Fourier transform-ion cyclotron resonance ion trap. For a given initial ion cyclotron phase and radius, ions of different initial z position are shown to be excited to significantly different ion cyclotron radii (and ultimately radially ejected at significantly different excitation amplitude-duration products). Ion initial z displacement from the trap midplane affects observed ICR signal magnitude in two ways: (1) for the same postexcitation cyclotron radius, an ion with larger initial z displacement induces a smaller ICR signal and (2) an ion with larger initial z displacement is excited to a smaller cyclotron radius. We also evaluate the induced ICR signal as a function of excitation amplitude-duration product for spatially uniform or Gaussian ion initial z distributions. In general, if the excitation waveform contains components at frequency, 2 omegaz or (omega+ + 2 omegaz, in which omegaz is the axial C"trapping") oscillation frequency, then ejection occurs axially. However, the resulting excitation amplitude-duration product for such axial ejection is significantly higher (factor of, ~ 4) than that required for radial ejection (at omega+) for ions of small initial radius. The present results offer the first explanation of how, even if the ion is initially at rest on the z axis (i.e., zero excitation electric field amplitude on the z axis), z ejection (axial ejection) may nevertheless occur if the excitation waveform contains frequency components at omega+ + 2omegaz and/or 2w z Namely, our simulations reveal that off-resonant excitation pushes ions away from the z axis, after which the ions are exposed to z excitation and eventual z ejection. PMID- 24222029 TI - A tandem mass spectrometric investigation of (C2H 5) 2X (+) ions (X = Cl, Br, I): The involvement of classical and nonclassical ethyl structures therein. AB - The formation of diethyl halonium ions (C2H5)2X(+) (X = Cl, Br, I) by a variety of ion-molecule reactions is described. The dissociation characteristics (metastable and collision-induced dissociation mass spectra) of these ions and their isomers were studied in detail. Some of the neutral fragmentation products were examined by their collision-induced dissociative ionization mass spectra.The participation of classical (1, CH3CH2X(+)CH2CH3) and nonclassical forms of the ions was considered. Dissociation reactions for which loss of positional identity of H-D atoms took place, for example C2H4 loss (a common fragmentation of metastable ions) and C2H5 (+) formation, were interpreted as involving nonclassical ions, 2. It was concluded that the ion-molecule reactions produced both ion structures, but in different halogen-dependent proportions. For (C2H5)2C1(+) ions, 2 is the major species, for (C2H5)2Br(+) both 1- and 2-type ions are generated, whereas for (C2H5)2I(+) the classical form 1 must be the predominant structure. PMID- 24222030 TI - Dissociation of proton-bound complexes and proton affinity of benzamides. AB - Proton-bound heterodimers of substituted benzamides 1-15 and N,N-dimethyl benzamides 16-30, respectively, with a series of reference bases were generated under chemical ionization conditions. Their dissociation into the protonated amide AH(+) and protonated reference base BH(+) was studied by metastable ion techniques and by collision-induced dissociation (CID) to examine substituent effects on the proton affinity (PA) of the benzarnides and to elucidate some aspects of the dissociation dynamics of proton-bound clusters. The PAs of the substituted benzarnides were determined by bracketing the amide by a pair of reference bases to give rise to more and less abundant signals of the protonated base in the mass-analyzed ion kinetic energy (MIKE) spectra of the proton-bound heterodimers. The substituent effects observed agree with O-protonation in both the primary and the tertiary benzamides. However, the susceptibility of the benzamide to polar substituent effects is remarkably small, which indicates a "resonance saturation"), of the amide group. The relative abundances of AH(+) and BH(+) in the MIKE and collisional activation (CA) mass spectra depend strongly on the pressure of the collision gas during CID, and in certain cases a reversal of the relative abundances with increasing pressure that favors the formation of BH+ from a less basic reference base is observed. Although this effect underlines the limited possibilities of the "kinetic method" for PA determination by CID of proton-bound heterodimers, it uncovers important kinetic effects during the dissociation of proton-bound heterodimers and of proton transfer reactions in the gas phase.. In the case of the protonated amide clusters, the observed intensity effects in the CA mass spectra are explained by a double-well potential energy surface caused by solvation of the protonated base by the polar amide in the protonated heterodimer. PMID- 24222031 TI - The decompositions of N-(substituted benzalamino)phthalimide radical cations embody ion-neutral complexes and Stevenson's rule. AB - A previously unreported series of N-(substituted benzalamino)phthalimides was investigated by using the combined techniques of high resolution electron ionization mass spectrometry, metastable decomposition, and collisional activation mass spectrometry. The predominate fragmentation pathway is a McLafferty-type rearrangement. There also occurs, to a lesser extent, a transfer of hydrogen that originates from a substituent remote from the phthalimide moiety and terminates on the phthalimide, The process is interpreted as proceeding via an ion-neutral complex. The effects of substituents on both of the aforementioned fragmentation pathways provide a striking example that gives quantitative evidence for Stevenson's rule. The substituent effects are responsible for a trend in ion abundance that shows a sharp reversal at approximately the ionization energy of the iminium isomer of the phthalimide molecular ion. PMID- 24222032 TI - Effects of target gas in collision-induced dissociation using a double quadrupole mass spectrometer and radiofrequency. AB - Collision-induced dissociation (CID) of polyatomic ions sampled from an rf powered glow discharge is examined by using three target gases including atomic (Ar and Xe) and molecular species (N2). Collisions with these targets in the first quadrupole of the double quadrupole system result in the loss of discharge species by dissociation, symmetric and asymmetric charge exchange, and scattering, each to varying degrees. These processes are seen to be a function of the relative mass, size... and ionization potentials of the target species, as well as the collision center-of-mass energies. In light of the comparisons, xenon appears to be the best collision target for both CID and charge exchange because of its relatively low ionization potential and high dissociation efficiency of polyatornic species. Evidence for both symmetric and asymmetric charge exchange is presented for Ar and Xe target gases. PMID- 24222033 TI - A particulate isotopic standard of uranium and plutonium in an aluminosilicate matrix. AB - Mixed-actinide microstandard particles have been produced for calibration and performance testing of isotope-ratio mass spectrometers and ion and electron microprobe instruments. The spherical micrometer-size particles consist of an aluminosilicate matrix loaded with 2.2% by weight of isotopically certified uranium and 0.11% by weight of isotopically certified plutonium. The uranium and plutonium isotopic compositions have been verified by both thermal ionization mass spectrometry and secondary ionization mass spectrometry (SIMS). The elemental composition of the microspheres has been determined by both electron microprobe and SIMS analysis. PMID- 24222034 TI - Optimization and testing of mass spectral library search algorithms for compound identification. AB - Five algorithms proposed in the literature for library search identification of unknown compounds from their low resolution mass spectra were optimized and tested by matching test spectra against reference spectra in the NIST-EPA-NIH Mass Spectral Database. The algorithms were probability-based matching (PBM), dot product, Hertz et al. similarity index, Euclidean distance, and absolute value distance. The test set consisted of 12,592 alternate spectra of about 8000 compounds represented in the database. Most algorithms were optimized by varying their mass weighting and intensity scaling factors. Rank in the list of candidatc compounds was used as the criterion for accuracy. The best performing algorithm (75% accuracy for rank 1) was the dot-product function that measures the cosine of the angle between spectra represented as vectors. Other methods in order of performance were the Euclidean distance (72%), absolute value distance (68%) PBM (65%), and Hertz et al. (64%). Intensity scaling and mass weighting were important in the optimized algorithms with the square root of the intensity scale nearly optimal and the square or cube the best mass weighting power. Several more complex schemes also were tested, but had little effect on the results. A modest improvement in the performance of the dot-product algorithm was made by adding a term that gave additional weight to relative peak intensities for spectra with many peaks in common. PMID- 24222035 TI - Micro-Electrospray: Zeptomole/attomole per microliter sensitivity for peptides. AB - The micro-electrospray ionization source has been optimized for the specific analysis of neuropeptides such as neurotensin and methionine enkephalin. The source has the option of integrating nanoliter flow-rate desalting and preconcentration techniques into the micro-electrospray spray needle, eliminating post-column dead volumes. For neurotensin, the most sensitive neuropeptide analyzed thus far in this work, the injection of 10 MUL of a solution containing 320 zeptomolesy/gmL gave an [M + 3H](+3) ion at m/z 558.4 with S/N of > 8?1. The MS/MS analysis of this peptide for the fragment ion at m/z 578.9 gave a S/N > 20?1 for a solution containing 32 attomoles/MUL. PMID- 24222037 TI - Network dynamics contribute to structure: nestedness in mutualistic networks. AB - Both ecological and evolutionary timescales are of importance when considering an ecological system; population dynamics affect the evolution of species traits, and vice versa. Recently, these two timescales have been used to explain structural patterns in host-parasite networks, where the evolution of the manner in which species balance the use of their resources in interactions with each other was examined.One of these patterns was nestedness, in which the set of parasite species within a particular host forms a subset of those within a more species-rich host. Patterns of both nestedness and anti-nestedness have been observed significantly more often than expected due to chance in host-parasite networks. In contrast, mutualistic networks tend to display a significant degree of nestedness, but are rarely anti-nested. Within networks with different interaction types, therefore, there appears to be a feature promoting non-random structural patterns, such as nestedness and anti-nestedness, depending on the interaction types involved.Here, we invoke the co-evolution of species trait values when allocating resources to interactions to explain the structural pattern of nestedness in a mutualistic community. We look at a bipartite, multi species system, in which the strength of an interaction between two species is determined by the resources that each species invests in that relationship. We then analyze the evolution of these interactions using adaptive dynamics.We found that the evolution of these interactions, reflecting the trade-off of resources, could be used to accurately predict that nestedness occurs significantly more often than expect due to chance alone in a mutualistic network. This complements previous results applying the same concept to an antagonistic network. We conclude that population dynamics and resource trade-offs could be important promoters of structural patterns in ecological networks of different types. PMID- 24222038 TI - Bacteria and lytic phage coexistence in a chemostat with periodic nutrient supply. AB - The dynamics of bacteria and bacteriophage coexistence was examined in a chemostat in which the externally driven supply of nutrient for bacteria, and washout rate oscillates periodically. The proposed mathematical model for three interacting variables, bacteria, phage, and nutrient, consists of 3 differential equations with time delay, due to the phage latent period of lysing. The study was carried out in an interval of physical parameters where an equivalent model with constant supply of nutrient and washout rate is mathematically unstable, running in limit cycle regimes, with known self-frequencies. It addresses mainly the asymptotically persistent dynamics of the system.Bifurcation maps in terms of two externally controlled parameters, the amplitude and frequency of the controlled nutrient supply were constructed for various latent lysis periods, in order to determine the frequency entrainment, i.e., the resulting main operating frequency of the system, relative to the known external and self-frequencies. Also presented are bifurcation maps for the rich variety of dynamical types observed in the study. Bifurcation diagrams in terms of the lysing time delay were also included for completion.A new type of entrainment, combining in a simple way the external and self-periods (reciprocal frequencies), is shown to exist for a range of parameters. PMID- 24222039 TI - Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. AB - Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process. PMID- 24222040 TI - Role of the neural pathway from hindbrain to hypothalamus in interaction of GLP1 and leptin in rats. AB - Glucagon-like peptide-1 (GLP1) and leptin are anorectic hormones. Previously, we have shown that i.p. coadministration of subthreshold GLP1 with leptin dramatically reduced food intake in rats. In this study, by using midbrain transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of GLP1 and leptin in reducing food intake. Food intake reduction induced by coinjection of GLP1 and leptin was blocked in midbrain-transected rats. These findings indicate that the ascending neural pathway from the hindbrain plays an important role in transmitting the anorectic signals provided by coinjection of GLP1 and leptin. PMID- 24222041 TI - An early-stage epidemic: a systematic review of correlates of smoking among Chinese women. AB - BACKGROUND: Despite the historically low smoking prevalence among Chinese women, there is a trend of future increase. PURPOSE: We systematically reviewed the correlates of smoking among Chinese girls and women. METHOD: We conducted a systematic review of literature on correlates of smoking among Chinese women using Medline and China Academic Journals databases. Following the PRISMA statement, two investigators independently searched for literature, identified and reviewed papers, assessed the quality of the papers, and extracted information. The characteristics of studies and correlates of smoking were synthesized separately for youth and adults. RESULTS: A total of 15 articles (11 on adults, 4 on youth) met the inclusion criteria. Based on these studies, peer smoking was the most consistent correlate of smoking among Chinese girls. Among Chinese women, partner smoking, job-related stress, and exposure to cigarettes made for women were consistent correlates of smoking. Knowledge of harms and negative attitudes towards smoking were found to be negatively associated with smoking. CONCLUSION: Overall, the evidence base for smoking among Chinese women is limited. Although smoking among Chinese women is still at an early stage, it is becoming more prevalent among specific population subgroups, such as rural-to urban migrant workers. Although further research is needed, findings from the current study provide a roadmap for research and policy on prevention of smoking among Chinese girls and women. PMID- 24222042 TI - Antioxidant neolignans from Cordia americana. AB - Five new neolignans with a bicyclo[2.2.2]octene framework were isolated from an ethanolic extract of the bark of Cordia americana. The structures and relative configurations of the compounds were elucidated by a combination of spectroscopic methods. All the isolated compounds showed good antioxidant activities in the DPPH radical scavenging (0.5-100 ug/mL) and Ferric-reducing antioxidant power (FRAP, 1-100 ug/mL) assays. One of the compounds displayed mild fungistatic activity at 0.1 umol/spot against Fusarium virguliforme while, at the same time, all compounds were inactive against several strains of Gram (+) and Gram (-) bacteria at all assayed concentrations (10-1,000 ug/mL). PMID- 24222044 TI - Endovascular stroke trials: why we must enroll all eligible patients. PMID- 24222043 TI - Vitamin D receptor-modulated Hsp70/AT1 expression may protect the kidneys of SHRs at the structural and functional levels. AB - Previous hypertension studies have shown that low levels of vitamin D are linked to elevated renin-angiotensin system. The heat shock protein 70 regulates signaling pathways for cellular oxidative stress responses. Hsp70 has been shown to protect against angiotensin II-induced hypertension and exert a cytoprotective effect. Here, we wanted to evaluate whether the vitamin D receptor (VDR) associated with Hsp70/AT1 expression may be involved in the mechanism by which paricalcitol provides renal protection in spontaneously hypertensive rats (SHRs). One-month-old female SHRs were treated for 4 months with vehicle, paricalcitol, enalapril, or a combination of both paricalcitol and enalapril. The following were determined: blood pressure; biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; and VDR, AT1 receptor, and Hsp70 expression in the renal cortex. Blood pressure was markedly reduced by enalapril or the combination but not by paricalcitol alone. However, VDR activation, enalapril or combination, prevented fibrosis, the number of TUNEL-positive apoptotic cells, mitochondrial damage, and NADPH oxidase activity in SHRs. Additionally, high AT1 receptor expression, like low Hsp70 expression (immunohistochemical/immunofluorescence studies), was reversed in the renal cortices of paricalcitol- and/or enalapril treated animals (SHRs), and these changes were most marked in the combination therapy group. Finally, all of the recovery parameters were consistent with an improvement in VDR expression. Data suggest that Hsp70/AT1 modulated by VDR is involved in the mechanism by which paricalcitol provides renal protection in SHRs. We propose that low AT1 expression through VDR induction could be a consequence of the heat shock response Hsp70-mediated cell protection. PMID- 24222045 TI - Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model. AB - BACKGROUND AND PURPOSE: The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture. METHODS: Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling. RESULTS: Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus. CONCLUSIONS: In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture. PMID- 24222046 TI - Formation and function of acute stroke-ready hospitals within a stroke system of care recommendations from the brain attack coalition. AB - BACKGROUND AND PURPOSE: Many patients with an acute stroke live in areas without ready access to a Primary or Comprehensive Stroke Center. The formation of care facilities that meet the needs of these patients might improve their care and outcomes and guide them and emergency responders to such centers within a stroke system of care. METHODS: The Brain Attack Coalition conducted an electronic search of the English medical literature from January 2000 to December 2012 to identify care elements and processes shown to be beneficial for acute stroke care. We used evidence grading and consensus paradigms to synthesize recommendations for Acute Stroke-Ready Hospitals (ASRHs). RESULTS: Several key elements for an ASRH were identified, including acute stroke teams, written care protocols, involvement of emergency medical services and emergency department, and rapid laboratory and neuroimaging testing. Unique aspects include the use of telemedicine, hospital transfer protocols, and drip and ship therapies. Emergent therapies include the use of intravenous tissue-type plasminogen activator and the reversal of coagulopathies. Although many of the care elements are similar to those of a Primary Stroke Center, compliance rates of >=67% are suggested in recognition of the staffing, logistical, and financial challenges faced by rural facilities. CONCLUSIONS: ASRHs will form the foundation for acute stroke care in many settings. Recommended elements of an ASRH build on those proven to improve care and outcomes at Primary Stroke Centers. The ASRH will be a key component for patient care within an evolving stroke system of care. PMID- 24222047 TI - Are acute stroke-ready hospitals ready? PMID- 24222048 TI - Death and family life in the past. AB - As recently as 1970 about one-fifth of the children living in single-parent households resided in ones created by the death of a father. In colonial and nineteenth-century America, death was a much more important factor in disrupting parent-child relationships than it is today. Past societal reaction to the death of a parent continues to influence social policy; for example, widows and their dependent children receive more public assistance than divorced mothers or single mothers with children born out-of-wedlock. Although the material conditions for widows have improved over time, the social network available to help them cope with the emotional distress caused by the death of a husband probably has diminished. PMID- 24222049 TI - Teenage childbearing as an alternative life-course strategy in multigeneration black families. AB - This paper summarizes the findings of a three-year exploratory qualitative study of teenage childbearing in 20 low-income multigeneration black families. Teenage childbearing in these families is part of an alternative life-course strategy created in response to socioenvironmental constraints. This alternative life course strategy is characterized by an accelerated family timetable; the separation of reproduction and marriage; an age-condensed generational family structure; and a grandparental child-rearing system. The implications of these patterns for intergenerational family roles are discussed. PMID- 24222050 TI - Evolution and sudden infant death syndrome (SIDS) : Part I: Infant responsivity to parental contact. AB - This paper and its subsequent parts (Part II and Part III) build on an earlier publication (McKenna 1986). They suggest that important clinical data on the relationship between infantile constitutional deficits and microenvironmental factors relevant to SIDS can be acquired by examining the physiological regulatory effects (well documented among nonhuman primates) that parents assert on their infants when they sleep together.I attempt to show why access to parental sensory cues (movement, touch, smell, sound) that induce arousals in infants while they sleep could possibly help one of many different subclasses of infants either to override certain kinds of sleep-induced breathing control errors suspected to be involved in SIDS or to avoid them altogether. I do not suggest that solitary nocturnal sleep "causes" SIDS, that all parents should sleep with their infants, or that traditional SIDS research strategies should be abandoned. However, using evolutionary data, I do suggest that an adaptive fit exists between parent-infant sleep contact and the natural physiological vulnerabilities of the neurologically immature human infant, whose breathing system is more complex than that of other mammals owing to its speech-breathing abilities. This "fit" is best understood, it is argued, in terms of the 4-5 million years of human evolution in which parent-infant contact was almost certainly continuous during at least the first year of an infant's life. Thus, to dismiss the idea that solitary sleep has no physiological consequences for infants does not accord with scientific facts. PMID- 24222052 TI - New approaches to the study of day care. PMID- 24222051 TI - Evolution and the sudden infant death syndrome (SIDS) : Part II: Why human infants? AB - Postnatal parent-infant physiological regulatory effects described in the previous paper (Part I) are viewed here as being biologically contiguous with events that occur prenatally, preparing and sensitizing the fetus to the average microenvironment into which the infant is expected, based on its evolutionary past, to be born. Following McKenna (1986), evidence (some of which is circumstantial) is presented concerning fetal hearing and fetal amniotic liquid breathing as they are affected both by maternal cardiovascular blood flow sounds in the uterus and by fluctuating maternal blood sugar levels. These data are linked in turn to the infant's postulated postnatal responsivity to parental sensory cues, including auditory and vestibular respiratory cues that may assist infants as they "learn" to breathe and, for some, to resist a SIDS event.Data on the respiratory and vocalizing behavior of normal and hearing-impaired persons are used to show that not all forms of human breathing are innate; some forms develop with experience. These data reveal how human infants learn, for example, to coordinate higher and lower brain respiratory nuclei in the context of learning initially to cry with intent and purpose and later to speak. Voluntary, cortex-based breathing emerges at the same time that infants are most likely to die from SIDS, between 2 and 4 months of age. This switch between voluntary and involuntary breathing during both sleep (while dreaming) and wake cycles, which depends on the integration of higher cortical and lower brain stem nuclei, is complex and is possibly the basis of the human species' unique susceptibility to SIDS-a syndrome as yet unrecognized in other species. These human infant vulnerabilities, including delayed maturity, can explain in part why natural selection ought to favor increased infant sensitivity to parental sensory cues provided by a caregiver-stimuli available in the evolving parental care environment that included parent-infant co-sleeping for more than 4-5 million years of human evolution. PMID- 24222053 TI - Urinary PCR as an increasingly useful tool for an accurate diagnosis of leptospirosis in livestock. AB - The aim of the present study was to consider the wide usage of urinary PCR as an increasingly useful tool for an accurate diagnosis of leptospirosis in livestock. A total of 512 adult animals (300 cattle, 138 horses, 59 goats and 15 pigs), from herds/flocks with reproductive problems in Rio de Janeiro, Brazil was studied by serology and urinary PCR. From the 512 serum samples tested, 223 (43.5 %) were seroreactive (cattle: 45.6 %, horses: 41.3 %, goats: 34%and pigs: 60 %). PCR detected leptospiral DNA in 32.4 % (cattle: 21.6 %, horses: 36.2 %, goats: 77.4 % and pigs: 33.3 %. To our knowledge there is no another study including such a large number of samples (512) from different species, providing a comprehensive analysis of the usage of PCR for detecting leptospiral carriers in livestock. Serological and molecular results were discrepant, regardless the titre, what was an expected outcome. Nevertheless, it is impossible to establish agreement between these tests, since the two methodologies are conducted on different samples (MAT - serum; PCR - urine). Additionally, the MAT is an indirect method and PCR is a direct one. In conclusion, we have demonstrated that urinary PCR should be considered and encouraged as an increasingly useful tool for an accurate diagnosis of leptospirosis in livestock. PMID- 24222055 TI - Polar [4+2(+)] diels-alder cycloaddition to nitrilium and immonium ions in the gas phase: Applications of multiple stage mass spectrometry in a pentaquadrupole instrument. AB - Multiple stage MS(2) and MS(3) mass spectrometric experiments, performed using a pentaquadrupole instrument, are employed to explore the gas-phase ion-molecule chemistry of several nitrilium [R-C=N(+)-H (1), R-C=N(+)-CH3 (2), and H-C=N(+) C2H5 (3)] as well as immonium ions RR(1)C=N(+)R(2)R(3) (4) with the neutral diene isoprene. Polar [4+2(+)] Diels-Alder cycloaddition is observed for nitrilium ions when the energy gap between the lowest unoccupied molecular orbital (LUMO) of the ion and the highest occupied molecular orbital (HOMO) of the isoprene is small and the competing proton transfer reaction is endothermic. Thus, C-protonated methyl isonitrile H-C=N(+)-CH3 (2a) and its higher homolog H-C=N(+)-C2H5 (3a) form abundant [4+2(+)] cycloadducts with isoprene, but several protonated nitriles 1 do not; instead they show exothermic proton transfer as the main ion molecule reaction. Replacement of the methyne hydrogen in 2a by a methyl, ethyl, or phenyl group (2b-d) raises the LUMO-HOMO gap, which greatly decreases the total yield of ion-molecule products and precludes cycloaddition. On the other hand, the electron-withdrawing acetyl and bromine substituents in 2e and 2f substantially lower the LUMO energy of the ions and cycloaddition reaction occurs readily. The simplest member of the immonium ion series, CH2=NH 2 (+) (4a), reacts readily by cycloaddition, whereas alkyl substitution on either the carbon or nitrogen (4b-f) dramatically lowers the overall reactivity, which substantially decreases or even precludes cycloaddition. In strong contrast, the N-phenyl (4g) and N-acetyl (4h) ions and the N-vinyl-substituted immonium ion, N protonated 2-aza-butadiene (4i), react extensively with isoprene, mainly by [4+2(+)] cycloaddition. However, the isomeric C-vinyl-substituted ion (4j) displays only modest reactivity in both the proton-transfer and the cycloaddition channels.Collision-induced dissociation (CID) of the cycloadducts performed by on line MS(3) experiments demonstrates that they are covalently bound and supports their assignments as cycloaddition products. Retro Diels-Alder fragmentation is a major process for cycloadducts of both the immonium and the nitrilium ions, but other fragmentation processes also are observed. The cycloadduct of 4a with butadiene displays CID fragmentation identical to that of the authentic ion produced by protonation of 1,2,3,6-tetrahydropyridine, which thus strengthens the [4+2(+)] cycloaddition proposal. AM1 calculations also support the formation of the [4+2(+)] cycloadducts, which are shown in several cases to be much more stable than the products of simple addition, that is, the ring-open isomers. PMID- 24222054 TI - Oncologists' and primary care physicians' awareness of late and long-term effects of chemotherapy: implications for care of the growing population of survivors. AB - PURPOSE: The population of cancer survivors is large and growing. Yet after successful completion of treatment, many experience chemotherapy-related late or long-term effects (LEs). The extent to which physicians are aware of LEs is unknown. METHODS: We conducted a nationally representative survey of 1,130 oncologists and 1,072 primary care providers (PCPs). Respondents were asked to select the LEs they had either observed or seen reported for five chemotherapy agents used to treat breast and colon cancers. We described and compared oncologists' and PCPs' awareness of the specified LEs. Using multivariate logistic regression models, we determined predictors of physicians' awareness of the main LEs associated with the agents. RESULTS: Almost all oncologists (95%) reported awareness of cardiac dysfunction as an LE of doxorubicin and peripheral neuropathy as an LE of paclitaxel (97%) and oxaliplatin (97%). These LEs were reported by 55%, 27%, and 22% of PCPs, respectively. Most oncologists reported awareness of premature menopause (71%) and secondary malignancies (62%) as LEs of cyclophosphamide, compared with only 15% and 17% of PCPs, respectively. Main LEs associated with all four agents were identified by 65% of oncologists and only 6% of PCPs. CONCLUSION: Although more than half of PCPs were aware of cardiac dysfunction as an LE of doxorubicin, awareness of other LEs was limited. Because PCPs may not be directly exposed to chemotherapy-related LEs, oncologists must communicate this information to PCPs as patients transition to primary care settings. Education for all providers caring for the growing population of cancer survivors is needed. PMID- 24222056 TI - Gas phase bimolecular chemistry of isomeric C3H 6Br (+) cations. AB - The gas phase chemistry of C3H6Br(+) cations generated via low energy electron impact on various dibromopropanes has been studied by using Fourier transform ion cyclotron resonance mass spectrometry. Neutral substrate molecules that have been selected to probe the bimolecular reactivity of the C3H6Br(+) isomers are ammonia, methylamine, trimethylamine, cis-butene, and 2, 3-dimethyl-2-butene. At least three different isomers are characterized on the basis of their different reactivity toward the various substrate molecules. It is suggested that these isomers have (a) the 2-bromo-2-propyl cation structure, (b) the propylenebromomum ion structure, and (c) the cyclic four-membered trimethylenebromonium ion structure. The 2-bromo-2-propyl cations react predominantely via proton transfer. This reaction is hampered for the propylenebromonium ions, which react mainly as electrophiles or bromanyl cation donors. Cyclic trimethylenebromoruum ions react predominantly via adduct formation, even under low pressure conditions, which implies that tturd body collisions are not the only stabilization mechanism. PMID- 24222057 TI - Reactive collisions in quadrupole cells. 3: H/D exchange reactions of protonated aromatic amines with ND3. AB - The H/D exchange reactions of a variety of protonated aromatic amines with ND3 m the collision cell of a hybrid BEqQ tandem mass spectrometer have been studied. The MH(+) ions were prepared by CH4, t-C4H10, and NH3 chemical ionization (CI) and, for some amines, by fast-atom bombardment (FAB). Evidence is presented that the kinetic energy of the incident ion as well as its internal energy must be dissipated by nonexchanging collisions before exchange occurs, once deactivated the MH(+) ions exchange efficiently, which leads, in most cases, to [MHJ(+) d x ions m which all active hydrogens have been exchanged. The MH(+) ion of 1,3 phenylenediamine formed by gas-phase CI exchanges only very slightly with ND3 whereas a significant fraction of the MH(+) ions formed by FAB exchange efficiently. This difference is rationalized in terms of dominant formation of the ring-protonated species in gas-phase CI reactions and significant formation of the N-protonated species by FAB with only the N-protonated species exchanging efficiently. Similar, although less pronounced, differences are observed for the MH(+) ion of m-anisidine. In a number of cases apparent exchange of aromatic hydrogens also is observed. Evidence is presented for the interchange of ring and amine hydrogens in protonated aromatic amines and it is suggested that only the N protonated species undergoes significant exchange with ND3. PMID- 24222058 TI - Molecular mass measurement of intact ribonucleic acids via electrospray ionization quadrupole mass spectrometry. AB - The use of electrospray ionization mass spectrometry for the accurate determination of molecular masses of polynucleotides and small nucleic acids is developed. The common problem of gas phase cation adduction that is particularly prevalent in the mass spectrometric analysis of nucleic acids is reduced through the use of ammonium acetate precipitations and by the addition of chemical additives that compete for adduct ions in solution. The addition of chelating agents such as trans-1,2-diaminocyclohexane-N,N,N,',N'-tetraacetic acid to remove divalent metal ions and triethylamine to displace monovalent cations from the analyte, in conjunction with ammonium acetate precipitation, reduces cation adduction to levels that permit accurate mass analysis (mass errors of less than 0.01%) without further complex cleanup procedures. The potential utility of accurate mass measurements of small ribonucleic acids is discussed. PMID- 24222059 TI - Analysis of hydroxy fatty acids as pentafluorobenzyl ester, trimethylsilyl ether derivatives by electron ionization gas chromatography/mass spectrometry. AB - Electron ionization (EI) gas chromatography/mass spectrometry (GC/MS) analysis of pentafluorobenzyl ester-trimethyl sllyl ether (PFB-TMS) derivatives of hydroxy subshtuted fatty acids provides structural information comparable to that obtained in analysis of methyl ester-trimethyl silyl ether (Me-TMS) derivatives. Use of this derivative eliminates the need to prepare two separate derivatives, the PFB-TMS derivative for molecular weight determination by electron capture ionization (negative ions) analysis and the Me-TMS derivative for structural determination by EI GC/MS analysis. The relative abundance of fragment ions observed during EI GC/MS analysis of these derivatized unsaturated fatty acids indicates the location of the -OTMS substituents relative to double bond positions in those cases studied. The most abundant fragment ions are observed when the compound contains an unsaturation two carbon atoms removed from the OTMS ether carbon (the beta-OTMS position). The "saddle effect" observed in the GC/MS analyses of some derivatized monohy- droxy unsaturated fatty acids is suggested to be due to a thermally allowed pericyclic double bond rearrangement and indicates the presence of a conjugated diene one carbon atom removed from the -OTMS ether carbon (the alpha-OTMS position). The saddle effect is most prominent for fatty acids that contain additional unsaturation separated by a single methylene unit from the conjugated diene moiety. PMID- 24222060 TI - Automated assignment of charge states from resolved isotopic peaks for multiply charged ions. AB - The recent proliferation of electrospray as an ionization method has greatly increased the ability to perform analyses of large biomolecules by using mass spectrometry. The major advantage of electrospray is the ability to produce multiply charged ions, which brings large molecules down to a mass-to-charge ratio range amenable to most instruments. Multiple charging is also a disadvantage because mass (m) becomes ambiguous unless charge (z) can be assigned. This is typically performed with simple algorithms that use multiple peaks of the same m and different z, but these methods are difficult to apply to complex mixtures and not applicable when only one z appears for each m. The use of mass analyzers with higher resolving powers, like the Fourier transform mass spectrometer, allows resolution of isotopic peaks, providing an internal 1-Da mass scale that can be used for unambiguous charge assignment. Manual assignment of charge state from the isotopic peaks is time consuming and becomes inaccurate when either the signal level or resolving power are low. For these cases, computer algorithms based on pattern recognition techniques have been developed to assist in assignment of charge states to isotopic clusters. These routines provide for more rapid analysis with higher accuracy than available manually. PMID- 24222061 TI - Multiparticle simulation of ion motion in the ion trap mass spectrometer: Resonant and direct current pulse excitation. AB - A PC-based program that simulates the behavior of a collection of ions is extended to include the effects of collisions with the buffer gas and enhanced visualization methods. The simulations are based on the quadrupole field associated with the actual ion trap electrode structure. Ionization is simulated in such a way as to distribute ionization events randomly over rf phase angles and yield a realistic collection of stored ions. The effects of buffer gas collisions on ion motion during both mass-selective instability and resonance ejection scans are found to include the expected dampening of spatial excursions as well as limitation of the kinetic energy of trapped ions. In both experiments, ion ejection occurs over a number of secular cycles in the vicinity of the theoretical instability point. Activation via a resonant ac signal or a short dc pulse is shown to result in phase-locking of the ions as well as the expected increase in the size of the excursions in the z direction and in ion kinetic energy. Collisions cause dephasing and loss of kinetic energy. Radial dc activation is compared with activation in the axial direction. Experimental data for dc pulse activation of the n-butylbenzene molecular ion are analyzed in phase space and the onset of surface-induced dissociation is correlated with changes in the experimental m/z 91 to m/z 92 fragment ion ratio. Poincare sections are shown for resonantly excited ions and their value in demonstrating improvement of the resolution of these experiments over conventional mass-selective instability scans is shown. PMID- 24222062 TI - Formation and characterization of the sulfur-containing distonic radical anion, [Formula: see text], in the gas phase, in the gas phase. AB - The reactions of the atomic oxygen radical anion O(-) with CH3-S-CH2-CN m the gas phase have been examined with Fourier transform ion cyclotron resonance in combination with tandem mass spectrometric experiments performed with a double focusing quadrupole hybrid instrument. Deuterium labeling has revealed that the O(-) ion reacts with CH3-S-CH2-CN by proton abstraction from the methylene group as well as by competing 1,1- and 1,3-H 2 (+) abstractions to afford isomeric radical anions. High kinetic energy (8 keV) collision-induced charge reversal experiments indicate that the 1,1-H 2 (+.) -abstraction leads to a [Formula: see text] carbene ion, whereas the 1,3-H 2 (+) abstraction yields a novel sulfur containing distonic radical anion, which is formulated as [Formula: see text]. PMID- 24222063 TI - Ion kinetic energy modulation for improved ion trapping in electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. AB - A new technique for manipulating the kinetic energy distribution of electrospray ions that arrive at a Fourier transform ion cyclotron resonance trapped-ion cell is presented. Narrow kinetic energy distributions can complicate the selection of appropriate trapping conditions for electrospray ions and introduce charge discrimination in resulting mass spectra. Modulation of the applied skimmer potential controllably broadens the kinetic energy distribution, which improves the reproducibility of acquired spectra and eliminates charge discrimination. Mass spectra of horse heart cytochrome c are presented to demonstrate the utility of the technique. For example, applied static skimmer potentials of 12 and 9 V yield charge state distributions ranging from [M+19H](+19) to [M+12H](+12) and [M+15H](+15) to [M+7H](+7), respectively. A 12 +/- 2 V, 100-Hz modulation of the skimmer potential yields an electrospray spectrum with charge states that range from [M+19H](+19) to [M+7H](+7), which is more representative of the source distribution. PMID- 24222065 TI - [Diagnostic yield and safety of bronchoscopic cryotechnique in routine diagnostics for suspected lung cancer]. AB - BACKGROUND: Cryoprobes with flexible catheters are an additional important tool for endobronchial interventional therapy and histologic diagnosis. Different studies compared the diagnostic effectiveness and complications to the forceps as a standard. However, routine endoscopic procedures require a combined use of different methods in order to achieve the highest diagnostic yield. We investigated the impact of cryotechnique in comparison with combined diagnostic tools during routine diagnostics of malignant tumors. PATIENTS AND METHODS: A consecutive series of patients undergoing routine diagnostic for lung cancer was included over a 30 months period (n = 469). The use of the cryotechnique, the complication rates and diagnostic value were prospectively documented. Cryotechnique was used on top of conventional technologies. RESULTS: A histologic proof of tumor by cryotechnique in centrally located tumors was delivered more frequently compared to forceps biopsies alone (81.4 versus 59.9% and 66.2 versus 37.7% in peripheral lesions). However, when the other non-cryotechniques were taken into account, the value was reduced in central probes (7.4%; p = 0.02), but remained high for peripheral findings (19.3%; p < 0.002). The frequency of complications seemed unchanged, however severe bleeding occurred. CONCLUSION: The cryotechnique bears high diagnostic potential beside its therapeutic value, also in routine investigations. The changed complication profile of this technology needs to be addressed in the informed consent and secured airway management may be helpful. PMID- 24222066 TI - [Implementation of the German guideline for the prevention, diagnosis, treatment and follow-up of non-small cell lung cancer at the Diakoniekrankenhaus Halle/Saale]. AB - BACKGROUND: More than three years since the release of the german guideline for the prevention, diagnosis, treatment and follow-up of lung cancer the database in terms of the implementation of guideline recommendations is deficient. The aim of this article is to analyze the implementation of the recommended algorithms for first-line therapy of non-small cell lung cancer. PATIENTS AND METHODS: On the basis of the patients records we determined all cases of newly diagnosed non small cell lung cancer which received a first-line therapy at the Diakoniekrankenhaus Halle/Saale between January 2010 and December 2011. The demographic data, tumor stage, time of diagnosis and performed first-line therapy were documented. Each case was assigned to the groups "guideline-adherent treatment" or "deviation from guideline recommendation" in dependency of its tumor stage. For this assignment the corresponding algorithms from guideline chapter "Therapy of non-small lung cancer" were used. RESULTS: A total of 126 from 148 cases (85%) received guideline-adherent treatment. Deviation from guideline recommendation was found in 22 cases (15%). The categories "poor performance status", "technical factors", "patient decision" and "others" were determined as the main reasons for non guideline-adherent treatment. CONCLUSIONS: Based on the analyzed population this study determined a high grade of guideline adherence at the period of investigation. Otherwise it shows that guideline recommendations cannot include each individual factor of the complex lung cancer disease. It could be found a wide range of reasons for deviation from the guideline recommendations. PMID- 24222067 TI - Fumonisin and T-2 toxin production of Fusarium spp. isolated from complete feed and individual agricultural commodities used in shrimp farming. AB - Fusarium spp. are plant pathogens producing fumonisins and trichothecenes that both affect human and animal health. In the present study, 40 fungal strains were isolated and species identified from 35 shrimp feed samples and from 61 agricultural raw materials. F. verticillioides was the predominant species (85 %) mostly found in corn and soybean meal, while no Fusarium contamination was detected in shrimp feed. Levels of 10 % of F. oxysporum were isolated from peanut and 5 % of F. equiseti contamination in corn and peanut. To determine the ability of toxin production, enzyme-linked immunosorbent assay, polymerase chain reaction, and ultra-pressure liquid chromatography-tandem mass spectrometry were performed. All but four of the fumonisin-producing strains contained the FUM1 gene. No Fusarium synthesized T-2 toxin nor contained the Tri5 gene. This survey brings more data on mycotoxin contamination in the food chain of animal feed production, and leads to the awareness of the use of contaminated raw materials in shrimp farming. PMID- 24222068 TI - Dedifferentiated laryngeal chondrosarcoma: combined morphologic and functional imaging with positron-emission tomography/magnetic resonance imaging. AB - Chondrosarcoma of the larynx is a rare, low-grade malignancy in terms of histology and clinical behavior. We present an unusual case of laryngeal chondrosarcoma, which developed a large dedifferentiated component on recurrence after primary surgery. The diagnosis of dedifferentiation was suggested in view of the morphological and metabolic findings on hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) and was subsequently confirmed surgically. Whole-organ, slice-by-slice radiologic-histologic correlation revealed excellent delineation of the well-differentiated and dedifferentiated tumor components with PET/MRI. PET/MRI can provide additional functional information to supplement the morphological mapping and histopathology of these tumors. PMID- 24222069 TI - HIV and HTLV-1 coinfection: the need to initiate antiretroviral therapy. PMID- 24222070 TI - Detection of noncovalent FKBP-FK506 and FKBP-Rapamycin complexes by capillary electrophoresis-mass spectrometry and capillary electrophoresis-tandem mass spectrometry. AB - The well known biospecific noncovalent receptor-ligand association complexes between the immunophilin FKBP and the immunosuppressive drugs FK506 and Rapamycin (RM) were investigated by on-line capillary electrophoresis-mass spectrometry (CE MS) under selected ion monitoring (SIM) conditions and by CE-MS with tandem mass spectrometry (CE-MS/MS) under selected reaction monitoring (SRM) conditions. Solutions of hFKBP (33.3 uM) were dissolved in 50 mM ammonium acetate at pH 7.5. Samples that contained 100 uM of FK506 or RM also were prepared under the same solution conditions. By using these aqueous pH neutral conditions, samples were analyzed by SIM CE-MS and SRM CE-MS and the target complexes were separated by CE with mass spectrometer detection of the individual complexes between FKBP and FK506 [hFKBP + FK506 + 7HJ(7+) as well as FKBP and RM [hFKBP + RM + 7HJ(7+). In an experiment where a mixture of FK506 and RM was analyzed in the presence of FKBP, a nine-to-one ratio of ion current abundances between the RM and FK506 complexes was observed as reported in the literature from other studies. These results suggest that CE-MS and CE-MS/MS may be yet another analytical method for studying noncovalent interactions of biologically important macromolecules under physiological conditions. PMID- 24222071 TI - Intrinsic basicity of oligomeric peptides that contain glycine, alanine, and valine-The effects of the alkyl side chain on proton transfer reactions. AB - The gas-phase basicities of oligomers of alanine and valine have been determined by bracketing measurements in an external source Fourier transform mass spectrometer. The results are compared to the oligomers of glycine, which were reported in an earlier publication, to observe the effect of the alkyl group and the increasing gas-phase basicity of the monomer units on the rates of proton transfer reactions. Molecular orbital calculations were performed on protonated triglycine and trialanine to determine how the alkyl groups affect intramolecular interactions. The results show that a high degree of ordering of the carbonyl groups is present in the protonated species. The carbonyl groups in turn order the side chain alkyl groups and decrease the rates of proton transfer reactions in, for example, the oligomers of valine. PMID- 24222072 TI - Ion trap collisional activation of the deprotonated deoxymononucleoside and deoxydinucleoside monophosphates. AB - Deoxymononucleoside and deoxydinucleoside monophosphate anions formed by electrospray have been subjected to ion trap collisional activation. The threshold for decomposition via loss of base is significantly lower for the deoxymononucleoside 3'-monophosphates than for the corresponding 5' monophosphates, which indicates that the presence of a charged 3' phosphate group facilitates base loss. The behavior of the bases among each class of isomers shows slight variation in threshold and tandem mass spectrometry efficiency with tile notable exception of 2'-deoxyguanosine 5'-monophosphate. This ion is exceptionally stable toward decomposition via base loss, which reflects a strong hydrogen bonding interaction between the base and the phosphate group. All dinucleotides fragment via similar mechanisms, but the propensity for neutral base loss relative to loss of a charged base is highly dependent on the identities of both the 5' and 3' bases. The behavior of the dinucleotides under collisional activation conditions supports the proposal that base loss proceeds via a proton-bound dimer intermediate in which loss of the charged base directly competes with loss of the neutral base. Application of the kinetic method allows for quantitative predictions of the differences of the gas-phase acidities of the dimer components. PMID- 24222073 TI - Formation of M(+) ions and electronic excitation under fast-atom bombardment conditions by using a liquid matrix. AB - Japan The mechanism for the formation of molecular ions M(+.) under fast-atom bombardment (FAB) conditions with a liquid matrix is discussed on the basis of the mass spectra of pyrene, coronene, and fullerene C60 obtained by using electron impact, gas-phase fast-atom bombardment, and gas-phase fast-molecule bombardment techniques. The obtained results suggest that formation of the M(+.) ions under FAB conditions is not due to direct collisions between analytes M and fast atoms A, but is due to collision interactions between M and recoiling matrix molecules B or matrix ions. It has been confirmed, furthermore, that the FAB conditions with a liquid matrix are sufficient in energy for formation of singly charged ions M(+.) and insufficient for the formation of multiply charged ions M (z+) (z=2, 3) of pyrene, coronene, and C60. PMID- 24222074 TI - Electron impact mass spectrometry of alkanes in supersonic molecular beams. AB - The electron impact mass spectrometry of straight chain alkanes C8H18-C40H82, squalane, methylstearate, 1-chlorohexadecane, 1-bromohexadecane, and dioctylphthalate was studied by sampling them with supersonic molecular beams. A fly-through Brink-type electron impact ion source was used, utilizing a vacuum background ion filtration technique based on differences between the kinetic energy of the supersonic beam species and that of thermal molecules. The 70-eV electron impact mass spectra of all the alkanes were characterized by a pronounced or dominant molecular weight peak together with all the fragment ions normally exhibited by the standard thermal 70-eV EI mass spectra. In contrast, the NIST library of most of these molecules did not show any molecular weight peak. By eliminating tile intramolecular thermal vibrational energy we gained control over the degree of molecular ion fragmentation by the electron energy. At an electron energy of 18 eV the molecular ion dissociation was further reduced considerably, with only a small absolute reduction in the peak height by less than a factor of 2. The effect of vibrational cooling increased with the molecular size and number of atoms. Pronounced differences were observed between the mass spectra of the straight chain triacontane and its branched isomer squalane. Similar mass spectra of octacosane (C28H58) achieved with 70-eV EI in a supersonic molecular beam were obtained with a magnetic sector mass spectrometer by using an electron energy of 14 eV and an ion source temperature of 150 degrees C. However, this ion source temperature precluded the gas chromatography mass spectrometry (GC-MS) of octacosane. The GC-MS of alkanes was studied with an ion trap gas chromatograph-mass spectrometer at an ion source temperature of 230 degrees C. Thermal peak tailing was observed for C20H42 and heavier alkanes, whereas for C28H58 and heavier alkanes the severe peak tailing made quantitative GC-MS impractical. In contrast, no peak tailing existed even with C40H82 for GC MS in supersonic molecular beams. The minimum detected amount of eicosane (C20, H42) was shown to be 60 fg. This was demonstrated by using single ion monitoring with the quadrupole mass analyzer tuned to the molecular weight peak of 282 u. The coupling of electron impact mass spectrometry in supersonic molecular beams with hyperthermal surface ionization and a fast GC-MS inlet is briefly discussed. PMID- 24222075 TI - Analysis of coumarins by micro high-performance liquid chromatography-mass spectrometry with a particle beam interface. AB - Coumarins are a large group of compounds that are naturally present in plant tissues and that exhibit a wide range of pharmacological properties. Analytical methods based on chromatographic techniques and conventional detectors are inadequate to accurately analyze coumarins in complex matrices such as plant extracts. In this article a new method based on a modified particle beam liquid chromatography-mass spectrometry interface is described. The method allows specific and accurate determination of several coumarins in biological matrices. An application regarding the analysis of 18 coumarins in the extract of Smyrnium perfoliatum L. is also reported. PMID- 24222076 TI - Direct generation of ion beam images with a two-dimensional charge injection device. AB - The use of a two-dimensional charge injection device (CID) to directly image the spatial profile of impingent positively charged ions is described. By this approach, no prior conversion from an ion beam to a photon image is required. Because of the positive response of the device to plasma photons, ions that emanated from the radiofrequency glow discharge source were diverted around a photon stop and focused onto the CID. The resultant ion images were digitized via an external image processor and corrected for dark current contributions. Two dimensional ion images and single pixel line profiles are presented. PMID- 24222077 TI - Characterization of anthraquinone-2-carbonyl chloride as an alcohol derivatization reagent for negative ion chemical ionization mass spectrometry. AB - Anthraquinone-2-carbonyl chloride has been utilized as a derivatization reagent for alcohols to impart electron affinity and aid in transport via a particle beam liquid chromatography-mass spectrometry (LC/MS) interface. In addition, the gas chromatographic-mass spectrometry, UV, fluorescence, and electrochemical characteristics of the derivatives were determined. A series of model compounds, 2-phenylethanol (phenethyl alcohol), 1-phenyl-2-propanol, 2-methyl-l-phenyl-2 propanol, hexanol, and methyl 2-methylglycerate, were used as analytes.The particle beam LC/MS properties of the resultant anthraquinone carboxylate esters were determined in electron impact (EI) and negative ion chemical ionization (NCI) modes. The NCI responses of these anthraquinone carboxylate esters were compared with the corresponding 3,5-dinitrobenzoate esters. The anthraquinone carboxylate esters exhibited an NCI to EI sensitivity enhancement of 113 and were detected in NCI at a tenfold lower concentration than the corresponding 3,5 dinitrobenzoate esters. A detection limit of 26 pg injected on column was achieved for phenethyl anthraquinone carboxylate in NCI by using selected ion monitoring. PMID- 24222080 TI - Antioxidant enzymes as defense mechanism against oxidative stress in midgut tissue and hemocytes of Bombyx mori larvae subjected to various stressors. AB - In this study, larvae of silkworm Bombyx mori were subjected to low temperature, hypoxia, and viral infection to evaluate stressor-mediated oxidative stress (OS) and the induction of antioxidant enzymes (AOEs). Exposure to cold, hypoxia, and nuclear polyhedral virus for 24 h resulted in a significant increase in hydrogen peroxide generation with concomitant increase in lipid peroxidation (LPO) and protein carbonyl levels in midgut and hemocytes. AOEs such as superoxide dismutase and catalase also increased significantly in both the tissues and the increased AOEs reverted to control values during recovery. Ontogenic stages of the larvae showed a diminishing ability of the tissues to overcome OS induced by the stressors. A significant increase in AOE activity during short stress period indicated a possible transitory defense mechanism to avoid OS-induced cell damage. PMID- 24222079 TI - Integrating novel therapeutic monoclonal antibodies into the management of head and neck cancer. AB - Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy. Interest in developing novel immunotherapies in HNSCC has been reawakened by the success of cetuximab, a therapeutic monoclonal antibody (mAb) against the epidermal growth factor receptor, which likely relies on immune as well as antisignaling mechanisms. This review focuses on novel therapeutic mAbs in current clinical development against established mechanisms of immune evasion in HNSCC, targeting: 1) tumor antigens, with resultant potential to induce antibody dependent cell-mediated cytotoxicity and T cell activation; 2) immunosuppressive cytokines; 3) costimulatory tumor necrosis factor-family receptors; and 4) coinhibitory immune checkpoint receptors. Clinical trials of immunotherapeutic mAbs as monotherapy, in combination with cytolytic standard therapies exposing tumor antigens or in combination with other immunomodulatory mAbs, are urgently needed in HNSCC. PMID- 24222082 TI - Co-immobilization of an enzyme and a metal into the compartments of mesoporous silica for cooperative tandem catalysis: an artificial metalloenzyme. PMID- 24222081 TI - Emotional well-being years post-treatment for breast cancer: prospective, multi ethnic, and population-based analysis. AB - PURPOSE: This study investigated factors associated with declines in emotional well-being (EWB) over time in breast cancer survivors. METHODS: Women with breast cancer (Stages I-III) residing in Los Angeles, CA, or Detroit, MI, and reported to the Surveillance, Epidemiology, and End Results registries between June 2005 and February 2007 completed surveys at 9 months and 4 years after diagnosis. EWB was measured by the Functional Assessment of Cancer Treatment-Breast. Using a stress coping framework, logistic regression models assessed associations between personal, social, and clinical correlates, appraisal (e.g., worry about recurrence) and coping factors (e.g., emotional support) to EWB declines. RESULTS: Among eligible women who completed primary breast cancer treatment, 772 completed both surveys, and 192 (24.9 %) experienced EWB declines over time. Women with past or current depression were more likely to report EWB decline (p < 0.01). Survivors who perceived they did not receive enough information about risk of breast cancer recurrence during primary treatment were more likely to have EWB decline (OR 0.53, 95 % CI 0.32-0.87). Greater perceived likelihood of recurrence (OR 1.95, 95 % CI 1.01-5.29) and increased worry about recurrence (OR 1.38, 95 % CI 1.10-1.72) were associated with EWB decline. Higher spirituality beliefs and practices were associated with EWB decline. CONCLUSIONS: A considerable number of breast cancer patients report emotional well-being declines over time. Early identification of women who are vulnerable, such as women with past depression, is crucial to improve quality of care. Women would benefit from education about cancer recurrence and tailored strategies to manage worry about recurrence over time. IMPLICATION FOR CANCER SURVIVORS: Understanding actual risk of recurrence and managing worry about recurrence is important for cancer survivors. Emotional concerns are common for individuals with cancer so survivors should feel free to reach out and discuss such concerns with providers well into the survivorship period. PMID- 24222083 TI - Giving between generations in American families. AB - This paper documents the types and amounts of aid exchanged between adults and their non-coresidential parents. Data for the study are drawn from a representative national sample survey of Americans age 19 and older conducted in 1987-1988. Exchanges of monetary and material resources, childcare, household assistance, and companionship and advice are considered.Patterns of intergenerational exchange are found to differ by gender, family structure, age, ethnicity, and socioeconomic situation. Differences in exchange between males and females and between whites and Mexican-Americans are related to other life-course characteristics, and to the availability and proximity of kin. Blacks and persons living in poverty are shown to be less involved than other groups in intergenerational exchanges. Finally, patterns of prior assistance and the available needs and resources of the respondents and their parents are found to influence current patterns of exchange. PMID- 24222084 TI - An evolutionary theory of cuisine. AB - The evolution of human diet is the product of both biological and cultural adaptations to various plants and animals in the environment. This paper develops a new theory for the evolution of cuisine practices which attempts to account for how food processing provided a critical link in enhancing the nutrient balance of major domesticated plants. PMID- 24222085 TI - Evolutionary explanations of emotions. AB - Emotions can be explained as specialized states, shaped by natural selection, that increase fitness in specific situations. The physiological, psychological, and behavioral characteristics of a specific emotion can be analyzed as possible design features that increase the ability to cope with the threats and opportunities present in the corresponding situation. This approach to understanding the evolutionary functions of emotions is illustrated by the correspondence between (a) the subtypes of fear and the different kinds of threat; (b) the attributes of happiness and sadness and the changes that would be advantageous in propitious and unpropitious situations; and (c) the social emotions and the adaptive challenges of reciprocity relationships. In addition to addressing a core theoretical problem shared by evolutionary and cognitive psychology, explicit formulations of the evolutionary functions of specific emotions are of practical importance for understanding and treating emotional disorders. PMID- 24222087 TI - Lipids and the liver. PMID- 24222086 TI - Evolution and the sudden infant death syndrome (SIDS) : Part III: Infant arousal and parent-infant co-sleeping. AB - This paper extends the evolutionary and developmental research model for SIDS presented in previous articles (McKenna 1990a, 1990b). Data from variety of fields were used to show why we should expect human infants to be physiologically responsive in a beneficial way to parental contact, one form of which is parent infant co-sleeping. It was suggested that on-going sensory exchanges (touch, movement, smell, temperature, etc.) between co-sleeping parent-infant pairs might diminish the chances of an infantile cardiac-respiratory crisis (such as those suspected to occur in some SIDS cases).In this article we review recent epidemiological data and sleep research findings on SIDS to show how they relate to evolutionary and cross-cultural perspectives. Results of a preliminary study of the co-sleeping behavior of mother-infant pairs indicate that, with respect to sleep, arousal, and respiratory patterns, co-sleeping mother-infant pairs affect each other in potentially important ways. We suggest specifically that co sleeping may shorten periods of consolidated sleep among young infants by causing them to arouse more frequently. Moreover, we suggest that partner-induced arousals might help the infant to confront sleep crises more competently. In the long run, these arousals might prevent the premature emergence of prolonged (adultlike) sleep bouts from which some infants have difficulty arousing especially during a breathing pause or apnea. PMID- 24222089 TI - The lipid droplet as a potential therapeutic target in NAFLD. AB - Nonalcoholic fatty liver disease (NAFLD) is a growing problem worldwide. Nonalcoholic fatty liver disease is characterized by an abnormal accumulation of triglyceride-rich lipid droplets (LDs) in the liver, which can lead to liver inflammation and metabolic disturbances. Lipid droplets are dynamic organelles that have recently gained considerable scientific interest. Their formation and growth are regulated processes requiring the participation of many endoplasmic reticulum- (ER-) and LD-associated proteins, which may serve as potential therapeutic targets for NAFLD. Protein families such as fat-inducing transmembrane proteins 1 and 2 (FITM1/FIT1 and FITM2/FIT2), the CIDE family of proteins, and the perilipin family, play important roles in LD biology. In this review, the authors discuss current views on LD formation and growth, and how various proteins may affect LD metabolism and lipoprotein assembly in the pathogenesis of NAFLD. PMID- 24222088 TI - Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. AB - The liver is a central organ that controls systemic energy homeostasis and nutrient metabolism. Dietary carbohydrates and lipids, and fatty acids derived from adipose tissue are delivered to the liver, and utilized for gluconeogenesis, lipogenesis, and ketogenesis, which are tightly regulated by hormonal and neural signals. Hepatic lipogenesis is activated primarily by insulin that is secreted from the pancreas after a high-carbohydrate meal. Sterol regulatory element binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) are major transcriptional regulators that induce key lipogenic enzymes to promote lipogenesis in the liver. Sterol regulatory element binding protein-1c is activated by insulin through complex signaling cascades that control SREBP-1c at both transcriptional and posttranslational levels. Carbohydrate-responsive element-binding protein is activated by glucose independently of insulin. Here, the authors attempt to summarize the current understanding of the molecular mechanism for the transcriptional regulation of hepatic lipogenesis, focusing on recent studies that explore the signaling pathways controlling SREBPs and ChREBP. PMID- 24222091 TI - Bile acid-mediated control of liver triglycerides. AB - Bile acids (BAs) are steroidal molecules generated in the liver by cholesterol oxidation. Beside their well-established role in lipid absorption and cholesterol homeostasis, they function as signaling molecules and activate dedicated BA receptors such as the farnesoid X receptor (FXR) and the G-protein coupled receptor TGR5. Through activation of downstream signaling pathways of these key receptors, BAs regulate not only their own synthesis and enterohepatic circulation, but also impact on hepatic lipid, glucose, and energy homeostasis. Therefore, BA-regulated signaling pathways have emerged as attractive targets for understanding the regulation of hepatic triglyceride metabolism in health and disease and treating fatty liver disease and associated metabolic disorders. PMID- 24222090 TI - The unfolded protein response in fatty liver disease. AB - The unfolded protein response (UPR) is a protective cellular response activated under conditions of endoplasmic reticulum (ER) stress. The hepatic UPR is activated in several forms of liver disease including nonalcoholic fatty liver disease (NAFLD). Recent data defining the role of the UPR in hepatic lipid metabolism have identified molecular mechanisms that may underlie the association between UPR activation and NAFLD. It has become increasingly evident that the IRE1alpha/Xbp1 pathway of the UPR is critical for hepatic lipid homeostasis, and dysregulation of this evolutionarily conserved pathway is associated with human nonalcoholic steatohepatitis (NASH). Although increasing evidence has delineated the importance of UPR pathway signaling in fatty liver disorders, the regulation of the hepatic UPR in normal physiology and fatty liver disorders remains incompletely understood. Understanding the role of the UPR in hepatic lipid metabolism may lead to the identification of novel therapeutic targets for the treatment of NAFLD. PMID- 24222093 TI - HCV and host lipids: an intimate connection. AB - The hepatitis C virus (HCV) requires elements of host lipid metabolism for every step in the viral life cycle. Clinically, it has long been observed that patients with chronic hepatitis C have lower nonhigh-density lipoprotein cholesterol, and these levels rise after successful treatment. The HCV itself circulates as a highly lipidated lipoviral particle, which closely resembles very low-density lipoprotein (VLDL). Several required coentry factors for the virus to gain access to the hepatocytes have been described, and several, including SRB1, LDL-R, and the NPC1L1 receptors, are important receptors for lipoprotein and cholesterol uptake. Inside the cell, the virus induces lipogenesis, and specifically induces the master regulator sterol response element binding protein. Viral replication then requires the concerted efforts of viral proteins combined with several host factors involved in cholesterol synthesis. The virus is then packaged alongside the cellular machinery for VLDL production. The complex interplay highlights pathways of hepatic steatosis and unveils drug targets for the treatment of HCV. PMID- 24222094 TI - PNPLA3-associated steatohepatitis: toward a gene-based classification of fatty liver disease. AB - Nonalcoholic fatty liver disease is one of the most common hepatic disorders worldwide. Given the high-calorie nutrition of children and adults, nonalcoholic fatty liver disease (NAFLD) is expected to become a major cause of cirrhosis and eventually liver transplantation. Familial clustering and ethnic differences indicate that genetic factors contribute to NAFLD. Recently, the common variant p.I148M of the enzyme adiponutrin (PNPLA3) has emerged as a major genetic determinant of hepatic steatosis and nonalcoholic steatohepatitis as well as its pathobiological sequelae fibrosis, cirrhosis, and hepatocellular cancer. PNPLA3 encodes a lipid droplet-associated, carbohydrate-regulated lipogenic and/or lipolytic enzyme. Homozygous carriers of the PNPLA3 variant are prone to develop cirrhosis in the absence of other risk factors such as alcohol or viral hepatitis. Here we review the plethora of studies that unraveled the association between PNPLA3 and NAFLD in children and adults, discuss its distinct effects on liver and metabolic traits, and introduce the term PNPLA3-associated steatohepatitis (PASH) as a novel gene-based liver disease. Given the prevalence of the risk allele in 40 to 50% of Europeans, the authors conclude that PNPLA3 should be considered in the diagnostic workup of fatty liver disease and that homozygous risk allele carriers might benefit from careful cancer surveillance. PMID- 24222092 TI - The role of gastrointestinal hormones in hepatic lipid metabolism. AB - Hepatocellular accumulation of free fatty acids (FFAs) in the form of triglycerides constitutes the metabolic basis for the development of nonalcoholic fatty liver disease (NAFLD). Recent data demonstrate that excess FFA hepatocyte storage is likely to lead to lipotoxicity and hepatocyte apoptosis. Hence, FFA mediated hepatocyte injury is a key contributor to the pathogenesis of nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis, obesity, type 2 diabetes, essential hypertension, and other common medical problems together comprise metabolic syndrome. Evidence suggests that peptide hormones from the L cells of the distal small intestine, which comprise the core of the enteroendocrine system (EES), play two key roles, serving either as incretins, or as mediators of appetite and satiety in the central nervous system. Recent data related to glucagon-like peptide-1 (GLP-1) and other known L-cell hormones have accumulated due to the increasing frequency of bariatric surgery, which increase delivery of bile salts to the hindgut. Bile acids are a key stimulus for the TGR5 receptor of the L cells. Enhanced bile-salt flow and subsequent EES stimulation may be central to elimination of hepatic steatosis following bariatric surgery. Although GLP-1 is a clinically relevant pharmacological analogue that drives pancreatic beta-cell insulin output, GLP-1 analogues also have independent benefits via their effects on hepatocellular FFA metabolism. The authors also discuss recent data regarding the role of the major peptides released by the EES, which promote satiety and modulate energy homeostasis and utilization, as well as those that control fat absorption and intestinal permeability. Taken together, elucidating novel functions for EES-related peptides and pharmacologic development of peptide analogues offer potential far-ranging treatment for obesity-related human disease. PMID- 24222096 TI - Steatohepatitis secondary to long-term glucocorticoid treatment for congenital adrenal hyperplasia: a potential diagnostic pitfall. AB - A 24-year-old woman with congenital adrenal hyperplasia (CAH) was referred for evaluation of elevated liver enzyme activities over the preceding 6 months. The patient was diagnosed with CAH at the age 12 when she presented with irregular menses and hirsutism. Since then, she had been on dexamethasone to maintain a normal menstrual cycle and prevent hirsutism and acne. She had no history of chronic liver disease and drank alcohol socially. An extensive workup for other treatable causes of liver disease was unrevealing. Therefore, a liver biopsy was performed, which revealed extensive ballooned degenerative hepatocytes containing Mallory-Denk hyalines. The ballooned hepatocytes were located predominantly in centrilobular areas and without any accompanying steatosis. Even though the histopathologic features are most compatible with alcoholic and/or nonalcoholic steatohepatitis, it was not supported by the patient's medical history and clinical presentation. The patient had a normal body mass index and only occasional alcohol use. Based on the biopsy finding and clinical presentation, we postulated that the abnormal liver enzyme and pathological features seen on the liver biopsy were secondary to CAH and long-term use of glucocorticoid. A few studies have shown that patients with CAH often develop metabolic abnormalities and insulin resistance, particularly women treated with glucocorticoid for several years. To our knowledge, this is the first report describing steatohepatitis secondary to CAH and prolonged glucocorticoid treatment. It is important to be aware that steatohepatitis can develop in these patients due to long-term glucocorticoid use and potentially lead to progressive liver damage. Furthermore, in patients with CAH who develop abnormal liver enzyme activities a liver biopsy is warranted to assess for steatohepatitis and any associated fibrosis. If indeed fibrosis is already present, a consultation with the endocrinologist should be undertaken in an effort to lower the dose of the glucocorticoids as much as possible while still controlling the symptoms of the disease. PMID- 24222095 TI - Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease. AB - Cardiovascular disease represents the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD exhibit an atherogenic dyslipidemia that is characterized by an increased plasma concentration of triglycerides, reduced concentration of high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) particles that are smaller and more dense than normal. The pathogenesis of NAFLD-associated atherogenic dyslipidemia is multifaceted, but many aspects are attributable to manifestations of insulin resistance. Here the authors review the structure, function, and metabolism of lipoproteins, which are macromolecular particles of lipids and proteins that transport otherwise insoluble triglyceride and cholesterol molecules within the plasma. They provide a current explanation of the metabolic perturbations that are observed in the setting of insulin resistance. An improved understanding of the pathophysiology of atherogenic dyslipidemia would be expected to guide therapies aimed at reducing morbidity and mortality in patients with NAFLD. PMID- 24222097 TI - Preservation of the inferior thyroidal vein reduces post-thyroidectomy hypocalcemia. AB - OBJECTIVES/HYPOTHESIS: We present a novel surgical method to preserve the inferior thyroidal vein and investigated its effectiveness in reducing postoperative transient hypocalcemia. STUDY DESIGN: Retrospective cohort study. METHODS: From January 2012 to October 2012, 109 total thyroidectomy patients with bilateral central neck dissection were included in this study. The controls were 96 sex- and age-matched patients who underwent a conventional total thyroidectomy from January 2011 to December 2011. Differences in the incidence of postoperative hypocalcemia, serial ionized calcium levels, and postoperative day 1 intact parathyroid hormone levels were analyzed using chi(2) and independent t tests. RESULTS: Age, male-to-female ratio, T stage, N stage, thyroid size, number of inadvertently excised parathyroid glands, operation time, number of harvested central lymph nodes, and total drainage amount were not significantly different between the groups. By saving the bilateral inferior thyroidal veins, the incidence of both biochemical and symptomatic hypocalcemia were significantly decreased compared to the controls (P = .044 and .012, respectively). The number of patients whose postoperative day 1 intact parathyroid hormones were <10 pg/mL was significantly lower in the study group (P = .000). Average ionized calcium levels were significantly higher in study-group patients; among the hypocalcemic patients, postoperative ionized calcium levels in the study group showed significantly faster recovery times than the control group. CONCLUSIONS: The described surgical method preserves the inferior thyroidal vein and may reduce post-thyroidectomy hypocalcemia without disturbing the extent of central lymph node harvesting. Preservation of the bilateral inferior thyroidal veins is important for reducing hypocalcemia and promoting faster recovery following thyroidectomy. PMID- 24222099 TI - No pathogenic GNAL mutations in 192 sporadic and familial cases of cervical dystonia. PMID- 24222098 TI - Reducing time-to-treatment in underserved Latinas with breast cancer: the Six Cities Study. AB - BACKGROUND: The interaction of clinical and patient-level challenges following a breast cancer diagnosis can be a significant source of health care disparities. Failure to address specific cultural features that create or exacerbate barriers can lead to less-than optimal navigation results, specifically in Hispanic/Latino women. METHODS: To address these disparities, the study leaders in San Antonio, Texas, and 5 other regional partners of the federally-funded Redes En Accion: The National Latino Cancer Research Network developed a culturally-tailored patient navigation intervention model for Latinas with breast cancer. RESULTS: Compared with control patients, a higher percentage of navigated subjects initiated treatment within 30 days (69.0% versus 46.3%, P = .029) and 60 days (97.6% versus 73.1%, P = .001) following their cancer diagnosis. Time from cancer diagnosis to first treatment was lower in the navigated group (mean, 22.22 days; median, 23.00 days) than controls (mean, 48.30 days; median, 33.00 days). These results were independent of cancer stage at diagnosis and numerous characteristics of cancer clinics and individual participants. CONCLUSIONS: Successful application of patient navigation increased the percentage of Latinas initiating breast cancer treatment within 30 and 60 days of diagnosis. This was achieved through navigator provision of services such as accompaniment to appointments, transportation arrangements, patient telephone support, patient-family telephone support, Spanish-English language translation, and assistance with insurance paperwork. PMID- 24222100 TI - A critical analysis of the concepts and measurement of awareness and equanimity in Goenka's Vipassana meditation. AB - Goenka's Vipassana meditation (GVM), a widely applied mindfulness training system rooted in Buddhism, is currently widely used. Although the two abilities cultivated in GVM, awareness and equanimity, exhibit certain similarities with the mindfulness cultivated in mindfulness-based psychotherapies (MBTs), they are not major concerns in MBTs. While many mindfulness scales have been created to measure different aspects of mindfulness constructs and certain scales and items can indeed reflect the basic abilities of awareness and equanimity, none of them can adequately capture the way in which those abilities and related ideas are applied in GVM. This paper presents a critical examination of the problems associated with the concepts and measurement of awareness and equanimity and presents potential solutions for achieving better measurement of these concepts in the future. PMID- 24222101 TI - Total Laboratory Automation of Routine Hemostasis Testing. AB - The aim of this study was to assess whether preanalytical management of coagulation samples through an open total laboratory automation system may impair the reliability of routine hemostasis tests as compared with loading of centrifuged plasma specimens directly into the coagulation analyzer for routine testing. Forty inpatient samples were divided into two aliquots. The former was centrifuged and directly loaded in a hemostasis analyzer, whereas the latter was entered into a 16.5 m long track-line system (FlexLab), where it was automatically centrifuged and conveyed to the same coagulation analyzer. An analytically significant difference was found between values of samples directly loaded in the coagulation analyzer and those entered in the track-line system for prothombin time (19.6 +/- 1.7 versus 19.2 +/- 1.6 s; p < 0.001) and activated partial thromboplastin time (38.0 +/- 1.4 versus 37.5 +/- 1.3 s; p = 0.021) but not for fibrinogen (305 +/- 12 versus 304 +/- 12 mg/dL; p = 0.97). Nevertheless, the mean percentage bias of prothombin time (-1.8%), activated partial thromboplastin time (-1.0%), and fibrinogen (0.4%) was modest and always lower than the total allowable error and was thereby considered not clinically significant. The results of this study confirm that connection of coagulation analyzers to track-line systems is a viable solution for modern clinical laboratories. PMID- 24222102 TI - The paradox of the unfolded protein response in cancer. AB - The endoplasmic reticulum (ER) is an elaborate organelle that is essential for cellular function and survival. Conditions that interfere with ER functioning can lead to the accumulation of unfolded proteins, which are detected by transmembrane sensors that then initiate the unfolded protein response (UPR) to restore ER proteostasis. If the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, particularly because ER stress-induced apoptosis is implicated in the pathophysiology of several diseases, including cancer. Whether the UPR inhibits tumour growth or protects tumour cells by facilitating their adaptation to stressful conditions within the tumour microenvironment is unknown, and dissection of the UPR network will likely provide answers to this question. In this review, we aim to elucidate the paradoxical role of the UPR in apoptosis and cancer. PMID- 24222104 TI - State of the art in the treatment of laryngeal cancer. AB - Nowadays clinics can offer patients a variety of different therapy options when laryngeal squamous cell carcinoma is diagnosed histologically. Depending on a variety of different factors, including tumor size, possible metastasis, health status and age of the patient, but also economic factors, a treatment schedule is established. Aim of every treatment decision should be organ larynx preservation and preservation of laryngeal function. The objective of this review is to give an overview of treatment modalities for laryngeal cancer, based not only on traditional but also on the latest studies regarding the treatment of this disease. Surgical approaches, as well as conservative treatment options, such as chemoradiotherapy, induction therapy and target therapy, are discussed. The optimal combination of surgical treatment and conservative treatment modalities need to be further investigated. Furthermore optimal laryngeal function as well as laryngeal preservation must be re-defined. PMID- 24222105 TI - Delivery approaches of gene therapy in hepatocellular carcinoma. AB - Gene therapy has the potential to provide therapeutic benefits to hepatocellular carcinoma (HCC) patients and has been the subject of intense pre-clinical and clinical research in recent years. In HCC, delivery of gene therapy has been attempted through multiple routes, using many vectors and genes in both animal models and patients. Unfortunately, a highly effective gene therapy for HCC has not been reported so far. The efficiency and selectivity of the gene transfer to the tumor tissue is too low. A great proportion of the failure can be attributed to the gene/vector complex itself. However, there is certainly a critical role played by the delivery technique. In the last decade a large amount of studies has been conducted to develop the ideal gene delivery technique for HCC, though questions regarding safety, repeatability, and efficiency still linger. The aim of this article is to review gene delivery techniques for HCC. It focuses on the relationship between the gene/vector complex and the delivery technique at promoting efficacy of gene therapy, without the cost of unacceptable systemic toxicity. The delivery techniques include systemic intravenous (IV) injection, intra-arterial (IA) injection, intra-tumoral (IT) injection, intra-portal (IP) injection, intra-biliary (IB) delivery and intra-splenic (IS) injection. The relative merits of each of these techniques are herein analyzed and discussed. PMID- 24222103 TI - Therapeutic value of quinazoline-based compounds in prostate cancer. AB - Certain alpha1-adrenoreceptor antagonists induce significant apoptosis and impair tumor vascularity without affecting cellular proliferation, effects specific to the quinazoline structure. These anticancer effects have been attributed to both induction of classical apoptosis and reversal of anoikis resistance via disruption of integrin-mediated cell survival pathways. Recent drug optimization efforts have generated several novel compounds with quinazoline-derived chemical structure that exert potent anti-tumor activity via anoikis. Results from pre clinical and clinical studies implicate a potential value of quinazoline-based analogues in prostate cancer prevention and therapy. A retrospective study of a large patient cohort at our center, revealed that treatment with alpha1 andrenoreceptor antagonists significantly reduced the risk of developing prostate cancer, indicating a potential chemopreventative mechanism for these FDA-approved agents. In the present review we discuss the current understanding of the signaling mechanisms reversing anoikis resistance by the quinazoline-based compounds in prostate tumors, towards enabling identification of novel therapeutic targets for the treatment of metastatic castration-resistant prostate cancer (CRPC). PMID- 24222106 TI - Targeting the Wnt/beta-catenin pathway in multiple myeloma. AB - BACKGROUND/AIM: Recent investigations have shown that the Wnt signaling pathway is constitutively activated in multiple myeloma (MM), thereby promoting an exaggerated cell proliferation. Thus, influencing the Wnt pathway might represent a promising target in myeloma treatment. MATERIALS AND METHODS: The present study investigated whether a combination of ethacrynic acid (EA) and ciclopirox olamine (CIC) with piceatannol (PIC) would influence the Wnt pathway and viability of human and murine myeloma cell lines by using DiOC6 and propidium iodide (PI) staining, flow cytometry and immunoblotting. RESULTS: The combination of EA with PIC as well as the combination of CIC with PIC had a significant additive effect on the vitality of myeloma cells compared to single-agent application, while healthy cells remained mainly unaffected. Additionally, EA and CIC altered the expression of beta-catenin itself and its downstream factors. CONCLUSION: A combination of Wnt inhibitors could lead to novel treatment options for MM patients. PMID- 24222107 TI - Growth inhibition by novel liposomes including trehalose surfactant against hepatocarcinoma cells along with apoptosis. AB - Novel liposomes composed of L-alpha-dimyristoylphosphatidylcholine (DMPC) and trehalose surfactant (DMTreCn) were produced by the method of sonication in buffer solution. The thickness of fixed aqueous layer of DMTreCn was larger than that of DMPC liposomes and increased in a dose-dependent manner. The remarkable inhibitory effects of DMTreCn on the growth of human hepatocellular carcinoma (HCC) (Hep-G2 and HuH-7) cells were obtained along with apoptosis, without affecting the growth of normal cells. DMTreCn induced apoptosis of Hep-G2 and HuH 7 cells through the activation of caspase-3, 8 and 9. Release of cytochrome c from mitochondria and activation of Bcl-2 family protein (BAX) were recorded, indicating that DMTreCn induced apoptosis of Hep-G2 and HuH-7 cells through mitochondrial pathway via BAX. It is noteworthy that the remarkable inhibitory effects of DMTreCn on the growth of human HCC cells were obtained along with apoptosis for the first time. PMID- 24222108 TI - Pre-clinical validation of orthotopically-implanted pulmonary tumor by imaging with 18F-fluorothymidine-positron emission tomography/computed tomography. AB - The development of positron-emission tomography (PET) and X-ray computed tomography (CT) imaging has improved the detection of tumor burden and, in turn, pre-clinical drug development and clinical treatment. In pre-clinical drug development, clinically-relevant murine cancer models, such as orthotopic models of lung cancer, have provided an accurate representation of tumor burden in humans. However, evidence demonstrating the capability of imaging-guided evaluation of these clinically-relevant models is limited. Here, we combined (18)F-fluorothymidine (FLT)-PET/CT imaging and a murine model of human non-small cell lung cancer (NSCLC) to improve the accuracy of anticancer drug evaluation in pre-clinical studies. We found that FLT-PET/CT imaging enabled the progression of pulmonary tumors to be longitudinally monitored rather than FDG-PET/CT. Furthermore, in an efficacy study of a standard treatment of docetaxel in a murine lung cancer model, FLT-PET imaging detected the anticancer response earlier than volumetric analysis by CT imaging. We, thus, observed a relationship between the alteration of FLT signals and Ki-67 index in the pulmonary tumor during the period of chemotherapy. These results indicate that the combination of FLT-PET/CT imaging and an orthotopic NSCLC model is an effective strategy for evaluating clinical efficacy and potential of an anticancer agent during pre clinical development. PMID- 24222109 TI - A preclinical murine model for the detection of circulating human tumor cells. AB - BACKGROUND/AIM: Circulating tumor cells (CTCs), cancer cells that disseminate from primary tumors and enter the bloodstream in the course of metastasis, may serve as an important indicator of metastatic disease and poor prognosis in patients with cancer. The aim of this study was to establish a preclinical animal model for detecting and studying human CTCs. MATERIALS AND METHODS: We performed a renal subcapsular implantation of human cancer cells in immunodeficient mice and recorded primary tumor growth, CTCs, and metastatic tumor development. RESULTS: Immunofluorescence, or immunohistochemical staining and whole-body imaging analysis revealed that the implanted cells developed primary renal tumors, CTCs were detected, and successfully established metastatic tumors in several organs, including the lung, colon, and lymph nodes, depending on the implanted cells. CONCLUSION: This model may be useful for detecting and characterizing CTCs and for investigating the mechanisms underlying the course of tumor metastasis. PMID- 24222111 TI - Chemoprevention with acetylsalicylic acid, vitamin D and calcium reduces risk of carcinogen-induced lung tumors. AB - BACKGROUND/AIM: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor. MATERIALS AND METHODS: A total of 60 A/J mice were randomized to a normal diet, a diet with low calcium, or a chemoprevention diet with acetylsalicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium. In addition to the diet, mice received carcinogens by oral gavage for ten weeks. RESULTS: The chemoprevention diet significantly reduced the number of animals with tumors [1 vs. 13, (p<0.001)] and the median number (range) of tumors [0 (0-1) vs. 1 (0-4), (p<0.001)] compared to controls. No signs of toxicity in relation to the diets were observed. CONCLUSION: The chemoprevention diet had a protective effect against tumor development in the mouse lungs. PMID- 24222112 TI - ID3 mutations are recurrent events in double-hit B-cell lymphomas. AB - BACKGROUND: Double-hit lymphomas (DHL) with chromosomal rearrangements affecting the avian myelocytomatosis viral oncogene homolog (cMYC) and either the B-cell lymphoma-2 (BCL2) or -6 (BCL6) locus are uncommon neoplasms with an aggressive clinical course and dismal prognosis. Most cases exhibit a phenotype intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Recently mutations affecting the inhibitor of DNA binding 3 (ID3), a helix-loop-helix protein regulating cell cycle progression and B-cell differentiation, were identified as being molecular hallmarks in Burkitt lymphoma, with only rare mutations being found in other lymphomas with translocations affecting cMYC. MATERIALS AND METHODS: In the present study, we evaluated the mutational status of ID3 in 37 cases of DHL and 16 cases of sporadic Burkitt lymphoma in order to identify a possible association of this new found hallmark with the rare and insufficiently-defined entity of DHL, seeking to broaden the understanding of these lymphomas at a molecular level. RESULTS: We identified ID3 mutations in lymphomas with chromosomal aberrations at cMYC and either BCL2 or BCL6 at a frequency intermediate between that of DLBCL and Burkitt lymphoma, hinting at a common pathway in lymphomagenesis for a subset of patients with DHL. CONCLUSION: The results of this study assist in the molecular characterization of these highly aggressive lymphomas, potentially giving rise to novel therapeutic approaches. PMID- 24222110 TI - Chemoprevention of oral cancer by lyophilized strawberries. AB - BACKGROUND/AIM: Oral cancer represents approximately 2.5% of all cancers in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. MATERIALS AND METHODS: HCPs were painted three times a week for six weeks with 0.2% 7,12-dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors was determined. RESULTS: A significant difference (p<0.01-0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. CONCLUSION: These experiments support previous studies in HCP that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer. PMID- 24222113 TI - Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population. AB - BACKGROUND: The distribution and kind of rat sarcoma viral oncogenes homolog (RAS) mutations, as well as their clinical impact on different types of thyroid lesions, vary widely among the different populations studied. We performed a comprehensive mutational survey in the highly related RAS genes HRAS, KRAS, and NRAS in a case series of proliferative thyroid lesions with known BRAF mutational status, originating from an ethnically diverse group. MATERIALS AND METHODS: Mutational hotspot regions encompassing codons 12, 13, and 61 of the RAS genes were directly sequenced in 381 cases of thyroid lesions. In addition, the putative NRAS hotspot region encompassing codon 97 was sequenced in 36 thyroid lesions. The case series included lesions of Hashimoto's thyroiditis (HT), nodular goiters, hyperplastic nodules, follicular adenomas (FAs), Hurthle cell variants of FA, papillary thyroid carcinomas (PTCs), follicular variants of PTC (FVPTCs), microcarcinomas of PTC (micro PTCs; tumor size <=1 cm), follicular TCs (FTCs), Hurthle cell variants of FTC, and non-well-differentiated TCs (NWDTCs). RESULTS: We identified RAS mutations in 16 out of 57 (28.1%) FAs, 2 out of 8 (25%) NWDTCs, 8 out of 42 (19.0%) FVPTCs, 2 out of 10 (20.0%) FTCs, 1 out of 12 (8.3%) Hurthle cell variants of FA, 3 out of 46 (6.5%) goiters, 1 out of 18 (5.6%) hyperplastic nodules, 3 out of 56 (5.4%) micro PTCs, 2 out of 115 (1.7%) PTCs, 0 out of 7 (0%) Hurthle cell variants of FTC, and 0 out of 10 (0%) HT lesions. NRAS codon 61 mutation was the predominant form, followed by HRAS codon 61 mutation. Only three mutations affected RAS codons 12 and 13, two of which were identified in goiters. No codon 97 mutation was detected in the examined FVPTCs. An as yet undescribed deletion of KRAS codon 59 was identified in one FA. DISCUSSION: RAS mutations in our case series were commonly associated with follicular-patterned thyroid lesions. Our data suggest that FAs with a RAS mutation may constitute precursor lesions for TC with follicular histology. The newly-discovered KRAS codon 59 deletion is one of the first reported codon deletions in a RAS hotspot region. PMID- 24222114 TI - MCP-1 promotes invasion and adhesion of human ovarian cancer cells. AB - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) can accelerate tumor progression by attracting tumor-associated macrophages. We studied the effects of MCP-1 on SKOV-3 cells in order to investigate MCP-1 biological activity ovarian cancer. MATERIALS AND METHODS: A SKOV-3 cell invasion assay (Transwell assay) and cell adhesion assay (96-well assay) were performed. Immunohistochemical staining for C-C motif chemokine receptor-2 (CCR2), a receptor for MCP-1, was also performed on cultured SKOV-3 cells. RESULTS: Migration and adhesion of MCP-1 treated SKOV-3 cells were significantly increased compared to untreated cells (p<0.01). A CCR2 antagonist attenuated the invasion and adhesion of MCP-1-treated cells. CCR2 was expressed in the cytoplasm of SKOV-3 cells. CONCLUSION: MCP-1 promoted invasion and adhesion of ovarian cancer cells, and a CCR2 antagonist attenuated the effects of MCP-1 in vitro. These data suggest that MCP-1 is a potential therapeutic target for ovarian cancer therapy. PMID- 24222115 TI - Impact of interleukin-10 on phenotype and gene expression during early monocyte differentiation into dendritic cells. AB - BACKGROUND: Cancer is linked to defects in immunosurveillance. Vaccination studies using dendritic cells (DC) try to re-establish immune responses toward tumor cells. Tumor-derived products such as interleukin-10 (IL-10) have inhibitory effects on DC function, and tumor-bearing hosts exhibit a lower number of DCs, suggesting inhibitory effects of tumor-derived factors on the recruitment of precursor cells. MATERIALS AND METHODS: We generated DCs in the presence and absence of IL-10. DCs were then characterized by flow cytometry and cDNA microarray analysis. RESULTS: IL-10 interferes with differentiation of peripheral blood monocytes to DCs and induces cells with a distinct phenotype. Microarray analysis revealed that IL-10 exhibits inhibitory as well as stimulatory effects on the expression of several genes. Addition of IL-10 to the differentiation cocktail induces a sustained inhibitory effect on subsequent maturation stimuli. CONCLUSION: IL-10 inhibits DC function and redirects differentiation of DCs to cells with a different phenotype, thereby reducing the pool of potential DC precursors. PMID- 24222116 TI - Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. MATERIALS AND METHODS: The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. RESULTS: HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. CONCLUSION: BA mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT. PMID- 24222117 TI - Identification of androgen-responsive microRNAs and androgen-related genes in breast cancer. AB - BACKGROUND: Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer. MATERIALS AND METHODS: We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line. We examined a possible correlation among microRNAs, target genes, and ARs in breast cancer tissues using immunohistochemistry and laser capture microscopy. RESULTS: Our analysis demonstrated that miR-363 and its possible target IQ motif and WD repeats-1 (IQWD1) are involved in a microRNA-mRNA pathway related to the mechanism of action of androgens. Our analyses showed that a high tumor level of IQWD1 in patients with breast cancer was significantly associated with adverse clinical outcomes. CONCLUSION: Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells. PMID- 24222118 TI - Human pancreatic cancer cells with acquired gemcitabine resistance exhibit significant up-regulation of peroxiredoxin-2 compared to sensitive parental cells. AB - Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine) is the only clinically effective drug for pancreatic cancer. However, high levels of inherent and acquired tumor resistance to gemcitabine lead to difficulty of chemotherapy for pancreatic cancer. We have reported on a proteomic study of gemcitabine-sensitive KLM1 and resistant KLM1-R pancreatic cancer cells, and identified some proteins which were shown to be up-regulated in KLM1-R compared to KLM1 cells. In those proteomic studies, peroxiredoxin-2 was listed as an up-regulated protein in KLM1-R cells. Peroxiredoxin-2 is a member of a family of peroxiredoxins providing a protective role for redox damage. In this study, the expression of peroxiredoxin-2 in KLM1 and KLM1-R cells was compared. It was found that peroxiredoxin-2 was significantly up-regulated in KLM1-R cells compared to KLM1 cells (p<0.001). However, peroxiredoxin-1 expression was significantly down-regulated in KLM1-R cells (p<0.001). These results suggest that peroxiredoxin-2 is a possible candidate biomarker for predicting the response of patients with pancreatic cancer to treatment with gemcitabine. PMID- 24222119 TI - Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro. AB - BACKGROUND: Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. MATERIALS AND METHODS: PANC-1 and AsPc-1 PDAC tumor cell lines were used. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells in each group were analyzed and the apoptotic index (AI) was calculated. RESULTS: PANC-1 cell line: HBO alone had no effect on AI: 6.5 +/- 0.1 vs. 5.9 +/- 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 +/- 0.1 (HBO-GEM), 8.5 +/- 0.1 (GEM HBO) vs. 8.1 +/- 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7 +/- 0.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9 +/- 0.1 vs. 5.9 +/- 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 +/- 0.1 (HBO-GEM), 8.4 +/- 0.1 (GEM HBO) vs. 8.0 +/- 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7 +/- 0.1 (p<0.001 vs. all groups). CONCLUSION: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cells in vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy. PMID- 24222120 TI - DNA methylation of MAPK signal-inhibiting genes in papillary thyroid carcinoma. AB - BACKGROUND: The purpose of this study was to identify the DNA methylation status of the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and serpin peptidase inhibitor A member 5 (SERPINA5) in thyroid cancer. MATERIALS AND METHODS: Using 76 papillary thyroid cancer(PTC) tissues and three thyroid cancer cell lines (TPC1, WRO82-1 and XTC), the expression of three genes and DNA methylation were determined by reverse transcription-PCR and methylation-specific PCR. RESULTS: In all cell lines, the expression of DUSP4 and DUSP6 increased; the corresponding gene promoters were unmethylated. However, SERPINA5 gene expression decreased and SERPINA5 DNA was methylated in the TPC1 cell line. With the de-methylating agent 5'-aza-2'-deoxycytidine, SERPINA5 gene expression was restored. In 82.9% of PTC tissues (63/76), the SERPINA5 DNA promoter was methylated, which was associated with a higher v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation rate in PTC tissues based on multivariate regression (odds ratio=3.573; 95% confidence interval=1.122-11.379; p=0.031). CONCLUSION: The expression of the MAPK signal inhibiting gene SERPINA5 decreased in the TPC1 cell line, SERPINA5 expression was regulated by DNA methylation, which was associated with a higher BRAF mutation rate in PTC. PMID- 24222121 TI - Protein-bound polysaccharide K reduced the invasive ability of colon cancer cell lines. AB - BACKGROUND/AIM: A protein-bound polysaccharide, polysaccharide K (PSK), is a non specific immunological agent used in the treatment of colon cancer, however few studies have investigated the genetic changes in cancer cells treated with PSK. Therefore, we investigated the effect of PSK on cancer cell invasion, which is an indicator for the malignancy of colon cancer cell lines, and performed additional genetic analyses. MATERIALS AND METHODS: We performed Matrigel invasion assay to examine whether the invasive ability of colon cancer cell lines HT29, HCT116, and LoVo would be impacted upon stimulation with PSK. We used reverse transcription polymerase chain reaction (RT-PCR) to evaluate for changes in the expression of matrix metalloproteinases (MMP)-2 and - 9 upon stimulation of colon cancer cell lines with PSK. RESULTS: The mean number of invasive cells in untreated HCT116, HT29, and LoVo cells was 146, 81, and 65, respectively, while that in PSK-treated cell lines was reduced to 24, 7, and 4, respectively. mRNA levels of MMP2 and MMP9 in PSK-stimulated cell lines were significantly lower than those in unstimulated cell lines. CONCLUSION: PSK reduced the expression of MMP2 and MMP9 mRNAs and cell invasion of this panel of colon cancer cell lines. PMID- 24222122 TI - Anticancer activity of a hydrogel containing folic acid towards MCF-7 and MDA-MB 231 cells. AB - AIM: The aim of the present study was to prepare a hydrogel, based on ellagic acid and glycine, embedded with folic acid, as a subcutaneous implant for the treatment of breast cancer. The function of folic acid is to selectively and actively target tumor cells which are well-known to overexpress folic acid receptors on their surface. MATERIALS AND METHODS: A pro-drug based on L-glycine and ellagic acid, was functionalized with a polymerizable group and loaded with folic acid to make it more natural, non-toxic, compatible and specific for the site of action. Cytotoxicity against MCF-7 cells was also evaluated. Release studies of folic acid were conducted on aliquots of hydrogel at different pH (6.2 and 7.4) and time-points (1, 6, 12 and 24 h) using a shaking water bath at 37 degrees C (body temperature). RESULTS: Our results show that folic acid release by the hydrogel is characterized by a slow kinetic release, especially at pH 6.2. Moreover, it was evidenced that the exposure of human breast cancer cells to ellagic acid-based hydrogel containing folic acid significantly reduced cell viability. PMID- 24222123 TI - Differential expression and prognostic role of selected genes in colorectal cancer patients. AB - AIM: Colorectal cancer (CRC) is one of the most common malignant diseases. The aim of our study was to describe the expression status of 12 selected candidate genes, by comparing paired samples of healthy colon mucosa and tumour tissues and to correlate obtained data with clinical and pathological features, with the goal of revealing associations for individual gene expressions and tumour behaviour. MATERIALS AND METHODS: Samples from 53 patients with CRC were analyzed. Patients were divided into two groups based on the presence or absence of distant metastases at the time of primary tumour surgery. Expression levels were assessed by quantitative real-time polymerase chain reaction. RESULTS: We found changes in the expression of 10 out of 12 analyzed genes. Four genes were significantly up regulated in tumour tissues: leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5; p<0.001), collagen triple helix repeat containing 1 (CTHRC1; p<0.001), visinin-like 1 (VSNL1; p<0.001) and versican (VCAN; p=0.001). Six genes were down-regulated: destrin (DSTN; p=0.004), mesoderm induction early response 1, family member 3 (MIER3; p<0.001), acyl-CoA synthetase long-chain family member 5 (ACSL5; p=0.002), mitogen-activated protein kinase 1/ERK (MAPK1; p<0.001), claudin 23 (CLDN23; p<0.001) and solute carrier family 26 (sulfate transporter), member 2 (SLC26A2; p<0.001). We recorded longer overall survival (OS) in the group of patients with higher expression of VSNL1 (p=0.032). Patients with more pronounced down-regulation of CLDN23 had shorter OS (p=0.045). In the group of patients without distant metastases, longer OS and disease-free interval (DFI) were found for patients with higher SLC26A2 expression in tumour tissues (p=0.036 and p=0.011, respectively). In the same group, lower expression of VSNL1 in healthy tissue corresponded to a longer DFI (p=0.020), smaller decrease of SLC26A2 and ACSL5 meant longer DFI (p=0.041 and p=0.040, respectively), as did greater increase of LGR5 expression (p=0.026). CONCLUSION: We identified differences in the expression of 10 genes in colorectal cancer tissue compared to healthy colon mucosa, and found prognostic significance for these changes which could be used for the development of a disease risk scoring system. PMID- 24222124 TI - Effects of chitosan on xenograft models of melanoma in C57BL/6 mice and hepatoma formation in SCID mice. AB - According to the World Health Organization, Complementary and alternative medicine (CAM) is a comprehensive term referring to traditional medical treatments and various forms of indigenous medicines, also known as indigenous or folk medicine. Cancer patients often use CAM in the form of nutritional supplements, psychological techniques and natural medical approaches in the place of or in parallel to conventional medicine. The present study aimed to determine if Chitosan can inhibit lung metastasis and hepatoma formation, by studying xenograft of B16F10 melanoma cells in C57BL/6 mice and of Smmu 7721 cells in SCID mice, respectively. For the lung metastasis model, after a five-week treatment, the survival rates of B6 mice were 15% for the control group and 35%, 20%, 45% and 40% for the 320,000 kDa, 173,000 kDa, 86,000 kDa and 8,000 kDa molecular weight treatment groups, respectively. Chitosan treatment dramatically increased lifespan and inhibited tumor metastasis especially in treatment groups of the low molecular weight compound. For the hepatoma growth model, the size of the liver tumor mass was approximately >14 mm in the control group. In comparison to the control group, the tumor mass grew slowly with Chitosan treatment, especially at the low-molecular weight treatment group. Chitosan slowed-down the rate of tumor growth but did not inhibit tumor formation. Data presented herein demonstrate that Chitosan has anticancer effects and thus further study of the substance is warranted to examine for mechanisms of action and optimal dosage. PMID- 24222125 TI - Co-existence of epithelioid and fibroblastoid subsets in a sarcomatoid renal carcinoma cell line revealed by clonal studies. AB - BACKGROUND: The biology of sarcomatoid renal cell carcinoma (RCC) and its conversion from and to the clear cell RCC are not fully-understood. We aimed to analyze the sarcomatoid RCC cell line, RCC52, derived from a lymph node metastatic lesion consisting mostly of sarcomatoid RCC cells with occasional clear cell areas. MATERIALS AND METHODS: Representative clonal epithelioid and fibroblastoid sublines isolated from the RCC52 cell line were analyzed alongside the parental line. Cytofluorometric and western blot analyses were used for phenotypic study. Xenotransplantation and in vitro invasive assays were used to determine tumorigenicity and invasiveness. Immunohistology in conjunction with antibodies to paired box gene-2 (PAX2) were used to determine if xenografts or tumor biopsies had the clear cell component. RESULTS: RCC52 cells grown as monolayers in vitro were all PAX2-negative, and consisted mostly of epithelioid cells and partly of fibroblastoid cells as noted in a previous study, confirming the co-existence of these two cell types in the in vitro growth of exclusive sarcomatoid RCC cells. Immunohistology revealed that the parental line and all epithelioid sublines tested were able to develop into solid tumors consisting mostly of sarcomatoid cells with PAX2-positive clear cells in some areas. The RCC stem cell marker CD105 was selectively expressed by a small proportion of the epithelioid, but not fibroblastoid, sublines, which was in line with the tumorigenic property of the epithelioid sublines containing cancer stem cells (CSCs). In contrast, only fibroblastoid sublines exhibited migratory/invasive properties, as determined by in vitro assays. CONCLUSION: Our findings confirm the presence of two distinct subsets in the RCC52 line, and suggest the epithelioid subset being able to de-differentiate to clear cells, albeit partially, and harboring CSCs as an emerging therapeutic target in order to achieve effective treatment of this malignancy. PMID- 24222126 TI - Synergistic anti-leukemic effects of CK2 inhibitors and pentabromobenzylisothioureas in vitro. AB - BACKGROUND: Casein kinase-2 (CK2) inhibitors and pentabromobenzylisothioureas are promising anti-leukemic agents for treatment, both alone and in combination. In this study, we examined pro-apoptotic and cytostatic effects of three CK2 inhibitors: one known, 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and two new: 2-(4-methylpiperazin-1-yl)-4,5,6,7-tetrabromo-1H-benzimidazole (MPT) and 2-aminoethyleneamino-4,5,6,7-tetrabromo-1H-benzimidazole (AEAT), as well as of certain S-2,3,4,5,6-pentabromobenzylisothiouronium bromides: ZKK-3, ZKK-9, ZKK 13, against the human acute myelogenous leukemia cell line (KG-1). Cells were treated with CK2 inhibitors alone and in combination with the pentabromobenzylisothioureas. MATERIALS AND METHODS: Evaluation of synergistic and pro-apoptotic effects, mitochondrial membrane potential (DeltaPsim) assay, poly(ADP-ribose) polymerase (PARP) cleavage assay, and cell-cycle progression of KG-1 cells were carried out using the flow cytometric technique and fluorescent microscopic analysis. Western blots were used for analysis of B-cell lymphoma-2 (BCL-2) family proteins in whole-cell extracts. RESULTS: The tested CK2 inhibitors DMAT, MPT, AEAT exhibited synergistic proapoptotic effect in combination with ZKK-3, ZKK-9 and ZKK-13. The agents revealed different pro apoptotic efficacies against leukemia cell line KG-1. The highest apoptotic activity of the tested compounds was exhibited by AEAT. CONCLUSION: Combination of CK2 inhibitors and pentabromobenzylisothioureas-induced synergistic anti leukemic effects against KG-1 acute myelogenous leukemia cells in vitro. PMID- 24222127 TI - Calcitonin-induced NF-kappaB activation up-regulates fibronectin expression in MG63 osteosarcoma cells. AB - Salmon calcitonin has been used extensively as a therapeutic tool in the regulation of bone remodeling. However, there is a growing body of evidence indicating that the calcitonin peptides are involved in regulation of cell growth, differentiation, survival and tissue development. In the present study, we investigated the effect of calcitonin in cell matrix interactions in MG63 cell line. Our results demonstrated that calcitonin increases cell growth of MG63 osteosarcoma cells in parallel with serine/threonine protein kinase B (AKT/PKB) activation. Moreover, calcitonin induced up-regulation of fibronectin expression in a nuclear factor-kappa B (NF-kappaB)-dependent manner, accompanied by enhanced enzymatic activity of matrix metalloproteinase-9 (MMP-9) and increased expression of tissue inhibitors of MMP-1 and -2. MMP-9 stimulation with calcitonin was accompanied by an increase in protein expression of the alpha5beta1 integrin receptor. To our knowledge, our results demonstrate, for the first time, that calcitonin is a potent inducer of fibronectin, an extacellular matrix component that is suggested to have a pro-oncogenic and healing effect, in a NF-kappaB dependent manner. PMID- 24222128 TI - Significant association of caveolin-1 (CAV1) genotypes with upper urothelial tract cancer. AB - AIM: Upper urothelial tract cancer is unusually of high incidence in Taiwan and it is valuable to study the specificity of this disease in Taiwan and compare the corresponding findings with those of Western countries. In the literature, it has been reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in risk of several types of cancer, such as hepatoma, leukemia, nasopharyngeal carcinoma, oral, breast, bladder and prostate cancer, but we are not aware of any reports on upper urothelial tract cancer. The aim of this study was to evaluate the association of six polymorphic genotypes of CAV1 with upper urothelial tract cancer within a Taiwanese population. MATERIALS AND METHODS: A total of 218 patients with upper urothelial tract cancer and 580 healthy controls in central Taiwan were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for six CAV1 polymorphic genotypes, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), and their association with upper urothelial tract cancer susceptibility was examined. RESULTS: The distribution of genotypes of CAV1 rs3807987 and rs7804372 were significantly different between cancer patient and control groups (p=0.0188 and 0.0090, respectively), while those for CAV1 rs1997623, rs12672038, rs3757733 and rs3807992 were not significant (p>0.05). The haplotype analysis of the two polymorphic genotypes showed that compared with the GG/AT, and GG/AA haplotypes of CAV1 rs3807987/rs7804372, those carrying GG/TT, AG/TT and AA/TT variants have a significantly increased risk of upper urothelial tract cancer (odds ratio=1.61, 1.50 and 2.67, 95% confidence interval=1.05-2.47, 1.18-1.90, and 1.37-5.18, respectively). On the contrary, other haplotype variants conferred non significant elevated risk. CONCLUSION: Our results suggest that individual and combined CAV1 rs3807987/rs7804372 genotypes are involved in predisposition to upper urothelial tract cancer in the Taiwanese population. PMID- 24222129 TI - Targeting biliverdin reductase overcomes multidrug resistance in leukemia HL60 cells. AB - BACKGROUND/AIM: Altered redox status has been reported to play a significant role in the development of multidrug resistance (MDR) in leukemia cells. Human biliverdin reductase (hBVR) has been recently identified as a major cytoprotectant; however, its role in MDR has not been yet investigated. In the present study we evaluated the possible role of hBVR in MDR development in the human HL60 leukemia cell line. MATERIALS AND METHODS: The relationship between hBVR and MDR was examined using the drug-sensitive HL60 cells and the drug resistant HL60 subline, HL60/ADR. A possible chemosensitization by siRNA pre treatment was also investigated. RESULTS: We observed that hBVR expression, protein, and enzymatic activity were significantly increased in multidrug resistant HL60 leukemia cells. We also found that knockdown of hBVR reverses multidrug resistance in resistant leukemic HL60 cells by a ROS-dependent mechanism. CONCLUSION: hBVR plays a pivotal role in the development of multidrug resistance in human HL60 leukemia cells. PMID- 24222130 TI - Shortened isoforms of the androgen receptor are regulated by the cytoprotective heat-shock protein HSPB1 and the tumor-suppressive microRNA miR-1 in prostate cancer cells. AB - BACKGROUND: Shortened, constitutively active androgen receptor (AR) isoforms have been characterized and linked to tumor progression and chemoresistance in prostate cancer (PCa). We examined the regulation of shortened AR isoforms by a newly-identified AR regulatory signaling pathway involving heat-shock protein HSPB1 and microRNA miR-1. MATERIALS AND METHODS: HSPB1 and miR-1 were modulated by overexpression and knock-down approaches utilizing the model PCa system, 22Rv1. Subsequently, AR isoform expression levels were quantified by western blot analysis. RESULTS: HSPB1 was identified as an inducer and miR-1 as an inhibitor of AR variants, with no detectable discrimination between long and short AR isoform regulation. CONCLUSION: In 22Rv1 cells, all AR isoforms were co-regulated by the cytoprotective factor HSPB1 and the tumor suppressor miR-1. Notably, our data provide evidence that HSPB1 inhibition is able to target expression of long as well as of short AR isoforms. PMID- 24222131 TI - 25-year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review. AB - AIM: To report long-term outcomes for HIV-positive patients who underwent radiation therapy (RT) for benign lymphoepithelial cysts (BLEC) of the parotid glands. PATIENTS AND METHODS: In this single institution retrospective study of HIV-associated BLEC of the parotids, the medical records of 37 HIV-positive patients who were treated with RT between 1987-2012 were reviewed. Patients were stratified into two groups; group A consisted of 15 patients (40.5%) who received a total dose of <=18Gy, with a median dose 10 Gy (range 8-18Gy), and group B consisted of 22 patients (59.5%) who received a total dose of 24 Gy. In addition to dosing information, additional patient data were collected, including demographics, HAART compliance, follow-up, and re-treatment status. RESULTS: The median age at the time of treatment was 41 (range=7-70) years. With a median follow-up of 35 (range=12-75) months for the entire cohort, the complete response (CR) and partial response (PR) rates were 35% and 8%, respectively. All but one of 15 patients in Group A (lower total dose) eventually experienced local failure with the re-emergence of parotid hypertrophy. Among the patients in group B (higher total dose of 24 Gy), 55%, 13%, and 32% experienced CR, PR, and LF, respectively. Median times to failure in groups A and B were 7 and 20 months, respectively (p<0.0001). Similarly, logistic regression test revealed the higher dose to be associated with better response rate (i.e. CR or PR) (p<0.0001), which was also statistically significant (p=0.03) after adjusting for confounding variables (age, race, gender, HAART use, and fractionation). CONCLUSION: A total dose of 24 Gy continues to be recommended for durable cosmetic control of BLEC of the parotid glands that is associated with HIV-seropositivity. PMID- 24222132 TI - Electrocardiography changes during adjuvant breast cancer therapy: incidence and risk factors. AB - BACKGROUND/AIM: Breast cancer survivors have a higher cardiovascular morbidity/mortality rate, when compared with healthy age-matched general population. Electrocardiography (ECG) changes have been found to be associated with chemo- and radiation therapy. In the present study we investigated changes in ECG patterns following modern adjuvant therapy for breast cancer. PATIENTS AND METHODS: A standard 12-lead electrocardiogram was recorded at rest three times (prior and after adjuvant therapy) and retrospectively analyzed in 414 breast cancer patients, who participated in the open prospective phase III randomized trial (BREX) of exercise training 2005-2007. RESULTS: New electrocardiographic changes in the T-wave or ST-segment (depression or elevation) after the adjuvant therapy were recorded in 49 patients (13%). In multivariate analyses, hypertension treated with anti-hypertensive medication was the only significant factor associated with irreversible ECG changes (OR=4.71; 95% CI=1.36-16.38; p=0.015). CONCLUSION: New irreversible pathological electrocardiographic changes, which acquired during the adjuvant therapy, had a clear relationship with hypertension This patients subgroup needs to be studied further. PMID- 24222133 TI - Bi-weekly paclitaxel and capecitabine as a second- or third-line treatment for advanced breast cancer: a pilot study. AB - BACKGROUND: Chemotherapy given every third week is currently the mainstay in the treatment of metastatic breast cancer (MBC). However, bi-weekly dosing might offer a better dose intensity, with better tolerability and response rates. This hypothesis was tested in a phase II study on bi-weekly paclitaxel combined with capecitabine. PATIENTS AND METHODS: Nineteen patients [median age was 60 (range: 43-68) years] with MBC were treated with paclitaxel (Taxol((r))) 120 mg/m(2), with 1-h infusion on days 1 and 15, and capecitabine (Xeloda((r))) 2650 mg/m(2)/day orally given at two doses on days 1-7 and 15-21 on a 28-day cycle. Metastatic sites included the bone (68%), lung (63%) and liver (47%), and 95% of patients had more than one sites of metastasis. RESULTS: In the response evaluation, one complete and 12 partial responses (overall response rate 68%), two stable disease cases and two progressive disease cases were observed. The median duration of response was 13.4 (range: 3.9-43.5) months. Progression-free and overall survival were 13 (95% CI=10.8-15.3) months and 23 (95% CI=17.7-29.1), respectively. A total of 140 (median 8, range 1-28) cycles were delivered. Grade 3-4 toxicity was uncommon: neutropenia was observed in 5% of the cycles; pulmonary problems in 1.4%; pain in 1.4%; and hand-and-foot syndrome, tiredness and arthralgia/myalgia, each in 0.7% of the study treatment cycles. CONCLUSION: Bi-weekly dosing of paclitaxel and capecitabine seems to yield promising responses in advanced breast cancer, with an acceptable adverse-event profile. PMID- 24222134 TI - Detection of cytomegalovirus DNA in colorectal tissue from Swedish and Vietnamese patients with colorectal cancer. AB - BACKGROUND: Human cytomegalovirus (HCMV) has been implicated as a factor, which might be associated with colorectal cancer (CRC) progression. Data from studies with HCMV-infected tumour cell lines have highlighted an oncomodulatory potential of HCMV. In the present study, we aimed to evaluate the prevalence of HCMV DNA in CRC tissue compared to matched normal tissue, and its association with clinical factors. PATIENTS AND METHODS: We used quantitative real-time polymerase chain reaction assay to detect HCMV DNA in 202 cancerous and paired normal tissue from Swedish (n=119) and Vietnamese (n=83) CRC patients. RESULTS: Overall, the HCMV DNA rate was significantly higher in cancerous in relation to paired normal tissue. Furthermore, a significantly higher frequency (39.8%) of HCMV DNA was observed in cancer tissues from the Vietnamese patients compared to the Swedish patients (15.1%). The prevalence of HCMV DNA in CRC tissue of 50% of those with disseminated disease tended to be higher compared to those with localized disease, with a prevalence of 33.3% in Vietnamese patients. CONCLUSION: Our observations indicate that the prevalence of HCMV DNA differs significantly between cancer and matched normal tissues. Thus, these data support a possible role of CMV in CRC. Moreover, we noted differences between Swedish and Vietnamese patients, indicating a role of ethnicity. PMID- 24222135 TI - Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy. AB - AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer. PMID- 24222136 TI - The feasibility and efficacy of stereotactic body radiotherapy for centrally located lung tumors. AB - AIM: To investigate the toxicity and outcome of stereotactic body radiotherapy (SBRT) for centrally-located lung tumors. PATIENTS AND METHODS: A retrospective review was conducted in 45 consecutive patients with centrally-located lung tumors who underwent SBRT. The incidence rate of adverse events (AEs) and outcome after SBRT for primary (32 patients), metastatic and recurrent (13 patients) lung tumors were evaluated. RESULTS: The median follow-up period was 21.2 months. Except for one patient who had grade 4 gastrointestinal toxicity, no patient exhibited any grade 4-5 AE. The 2-year overall survival of patients with primary non-small cell lung cancer (NSCLC) was significantly better than that of those with metastatic and recurrent tumors of 69.4% vs. 46.9% (p=0.04). The local control rates at two years, for patients in the NSCLC and the metastatic/recurrent groups were 70.9% and 100%, respectively (p=0.98). CONCLUSION: SBRT provided effective treatment for centrally-located lung tumors with tolerable toxicity. PMID- 24222137 TI - The E3 ubiquitin ligase SIAH2 is a prosurvival factor overexpressed in oral cancer. AB - BACKGROUND: This study aimed at investigating the expression and functional significance of seven in absentia homologues 2 (SIAH2), an E3 ubiquitin ligase, in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Comparative genomic hybridization and real-time PCR were performed to examine the amplification of SIAH2 gene in clinical specimens of OSCC tissues. Expression of SIAH2 mRNA and protein was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical assays, respectively. Apoptosis was examined by annexing V staining and Poly (ADP-ribose) polymerase (PARP) cleavage, with or without sienna-mediated SIAH2 knockdown. The expression of p53 was analyzed by immunoblotting. RESULTS: Levels of SIAH2 DNA and mRNA were significantly greater in clinical OSCC specimens and in cultured OSCC cells, which also stained positively for the SAIH2 protein. Knockdown of SIAH2 led to growth suppression and apoptosis induction in a p53-independent mechanism. CONCLUSION: These results revealed a tight correlation of SIAH2 overexpression with OSCC and suggest an oncogenic role of SIAH2 in oral cancer. PMID- 24222138 TI - Concordance of HER2 status in primary tumour and lymph node metastases in patients with esophageal carcinoma. AB - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an important prognostic factor in several types of solid tumours. Although HER2 seems not to influence survival in esophageal carcinomas, an impact of the HER2 status of disseminated tumour cells (DTCs) on survival has been shown. The aim of our study was to investigate the significance of the HER2 status in primary esophageal carcinomas and matched lymph node metastases. MATERIALS AND METHODS: The HER2 status of primary tumours and matched lymph node metastases were analysed for 158 patients with esophageal carcinoma using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). RESULTS: The study specimen included 90 adenocarcinomas (AC) and 68 squamous cell carcinomas (SCC). HER2 amplification was found in 12% and overexpression in 8.9% of all primary tumours. HER2 amplification was identical in the primary tumour and lymph node metastases in all AC and in 75% of SCC. Discordant-positive HER2 lymph node status and negative primary tumour status was found in 4.4% of AC and 1.5% of SCC in FISH analyses. No significant associations were found between HER2 amplification/overexpression and overall survival. CONCLUSION: HER2 gene status remains highly conserved in metastatic esophageal carcinoma. Discrepancies occur rarely between primary tumour and lymph node metastases and might be due to heterogeneity of the HER2 status of the primary tumour. This could be the reason for heterogeneity of DTCs and may result in metastasis of only a subset of tumour cells. PMID- 24222139 TI - Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study. AB - AIM: To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). PATIENTS AND METHODS: Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). RESULTS: A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (p<0.0001), higher percentage of African American women (p<0.0001), lower tumor grade (p<0.0001), higher number of dissected lymph nodes (LN) (p<0.0001), and less utilization of adjuvant radiation therapy (p=0.0003). Overall survival was improved in women in the BB generation compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African American race, and increased number of dissected LN. CONCLUSION: Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted. PMID- 24222140 TI - Radiation therapy for stage IVA cervical cancer. AB - BACKGROUND: To evaluate the outcome and discover predictive factors for patients with stage IVA cervical cancer treated with definitive radiation therapy. PATIENTS AND METHODS: We retrospectively reviewed 34 patients with stage IVA cervical cancer who received definitive radiation therapy between 1992 and 2009. RESULTS: On univariate analysis, statistically significant prognostic factors for improved local control rate (LCR) were absence of pyometra (p=0.037) and equivalent dose in 2 Gy fractions (EQD2) at point A greater than 60 Gy (p=0.023). Prognostic factors for improved progression-free survival (PFS) were absence of pelvic lymph node metastasis at initial presentation (p=0.014), and EQD2 at point A greater than 60 Gy (p=0.023). CONCLUSION: Patients with stage IVA disease had poor median survival. However adequate radiation dose to point A produced favorable LCR and PFS, therefore efforts should be made to increase the point A dose. PMID- 24222141 TI - Predicting skin toxicity according to EGFR polymorphisms in patients with colorectal cancer receiving antibody against EGFR. AB - BACKGROUND/AIM: Monoclonal antibodies against epidermal growth factor receptor (EGFR) can extend progression-free survival (PFS) and overall survival (OS) in patients with unresectable colorectal cancer; however, skin toxicity often interferes with therapy continuation. PATIENTS AND METHODS: We analyzed the polymorphisms in EGFR and IgG fragment C receptor (FCGR) genes and determined their associations with clinical outcomes including PFS, OS, and skin toxicity. Five polymorphisms in EGFR and FCGR genes in 32 patients with unresectable colorectal cancer who were treated with antibodies against EGFR were examined. RESULTS: Patients carrying the C/C genotype of the EGFR D994D polymorphism displayed significantly less skin toxicity than those with other genotypes, although no significant differences in PFS and OS were noted and no significant interactions were detected for other gene polymorphisms. CONCLUSION: These results suggest that the EGFR D994D polymorphism is a useful biomarker for predicting the severity of skin toxicity in patients receiving antibody against EGFR. PMID- 24222142 TI - A retrospective analysis of two different sequences of therapy lines for advanced kidney cancer. AB - BACKGROUND/AIM: the ideal sequence of targeted agents for advanced kidney cancer is still unknown. In the present study we assessed the clinical benefit of two different sequential approaches, namely sorafenib, an inhibitor of mammalian target of rapamycin (mTORi) and sunitinib, or sunitinib (an mTORi) and sorafenib. PATIENTS AND METHODS: we retrospectively reviewed the outcome of 40 advanced kidney cancer patients treated with one of the two above sequences. RESULTS: a total of 26 patients were treated with the sequence sorafenib-mTORi-sunitinib and 14 with the sequence sunitinib-mTORi-sorafenib. The actuarial overall median progression-free survival (PFS) in the sorafenib-mTORi-sunitinib group and in the sunitinib-mTORi-sorafenib group were 21.9 and 22.8 months, respectively (log-rank test: p=0.928). In the sorafenib-mTORi-sunitinib group, patients in first-, second- and third-line therapy experienced PFS of 11.7, 5.1 and 9.1 months, respectively, while in the sunitinib-mTORi-sorafenib group PFS was 14.4, 4.3, and 3.9 months, respectively. CONCLUSION: Our results suggest there is no significant difference between the two sequence modalities. PMID- 24222143 TI - A novel postoperative inflammatory score predicts postoperative pancreatic fistula after pancreatic resection. AB - AIM: The aim of this study was to characterize a high-risk group of patients for pancreatic fistula (PF) after pancreatic resection using postoperative clinical variables of patients. PATIENTS AND METHODS: The retrospective study included 297 patients who underwent pancreatic resection between January 2001 and December 2011. We examined the relationship between perioperative findings and the incidence of postoperative PF (POPF) among patients who underwent pancreatic resection between 2001 and 2009 (early period). Next, patients were stratified into three groups using serum albumin and CRP on postoperative day 1 (score 0: albumin >=2.7 g/dl and CRP <=10 mg/dl; score 1: albumin <2.7 g/dl or CRP >10 mg/dl; score 2: albumin <2.7 g/dl and CRP >10 mg/dl) as postoperative inflammatory score (PIS). We examined perioperative findings including PIS and POPF among patients who underwent pancreatic resection between 2010 and 2011 (late period). RESULTS: In univariate and multivariate analyses, male gender (p=0.032), serum albumin on postoperative day 1 (p=0.024) and serum CRP on postoperative day 1 were identified as independent risk factors for POPF in early period patients. In univariate and multivariate analyses, postoperative hospital stay (p=0.009) and PIS (score 1: p=0.005, score 2: p=0.017) were identifical as independent risk factors for POPF in late-period patients. CONCLUSION: We found a novel PIS to indicate risk for PF after elective pancreatic resection. PMID- 24222144 TI - Transumbilical defunctioning ileostomy: A new approach for patients at risks of anastomotic leakage after laparoscopic low anterior resection. AB - BACKGROUND: The use of a protective defunctioning stoma in rectal cancer surgery has been reported to reduce the rates of reoperation for anastomotic leakage, as well as mortality after surgery. However, a protective defunctioning stoma is not often used in cases other than low rectal cancer because of the need for stoma closure later, and hesitation by patients to have a stoma. We outline a novel and patient-friendly procedure with an excellent cosmetic outcome. This procedure uses the umbilical fossa for placement of a defunctioning ileostomy followed by a simple umbilicoplasty for ileostomy closure. PATIENTS AND METHODS: This study included a total of 20 patients with low rectal cancer who underwent a laparoscopic low anterior resection with defunctioning ileostomy (10 cases with a conventional ileostomy in the right iliac fossa before March 2012, and 10 subsequent cases with ileostomy at the umbilicus) at the Jikei University Hospital in Tokyo from August 2011 to January 2013. The clinical characteristics of the two groups were compared: operative time, blood loss, length of hospital stay and postoperative complications of the initial surgery, as well as the stoma closure procedure. RESULTS: There were no differences between the groups in the median operative time for initial surgery (248 min vs. 344 min), median blood loss during initial surgery (0 ml vs. 115 ml), and median hospital stay after initial surgery (13 days vs. 16 days). Complication rates after the initial surgery were similar. There were no differences between the groups in median operative time for stoma closure (99 min vs. 102 min), median blood loss during stoma closure (7.5 ml vs. 10 ml), and median hospital stay after stoma closure (8 days in both groups). Complications after stoma closure such as wound infection and intestinal obstruction were comparable. Thus, no significant differences in any factor were found between the two groups. CONCLUSION: The transumbilical protective defunctioning stoma is a novel solution to anastomotic leakage after laparoscopic rectal cancer surgery, with patient-friendliness as compared to conventional procedures in light of the cosmetic outcome. PMID- 24222145 TI - VEGF expression and response to sunitinib in patients with metastatic clear cell renal cell carcinoma. AB - AIM: To verify whether vascular endothelial growth factor (VEGF) is associated with distant metastasis free survival (DMFS) and Overall Survival (OS) of patients with renal cell carcinoma (RCC) treated with sunitinib. PATIENTS AND METHODS: We have studied 41 patients with metastatic RCC treated with radical nephrectomy, between 2008 and 2010, and sunitinib. Pathological features were compared with the Memorial Sloan-Kettering Cancer Center (MSKCC) score, DMFS, and with OS, and PFS after first-line therapy. RESULTS: Tumor stage and grade, VEGF expression and H-score correlated with MSKCC score, DMFS, and with OS; VEGF expression correlated with stage and OS. Patients with higher H-score and higher VEGF expression had a significantly shorter survival; OS after first-line sunitinib therapy and PFS correlated with MSKCC score and DMFS but not with VEGF expression and H score. CONCLUSION: Our data suggest the potential use of tumor cell VEGF expression as a prognostic marker for DMFS and OS, but VEGF does not appear promising as a marker of response to therapy. PMID- 24222146 TI - Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. AB - BACKGROUND: Endoscopic treatment has been increasingly used for T1 esophageal squamous cell carcinoma (ESCC). However, this therapy is sometimes incomplete if the depth of the T1 primary tumor reaches the muscularis mucosae or submucosal layer because these tumors have a relatively high incidence of lymph node metastasis. However, to our knowledge, no previous reports on the prediction of nodal metastasis determined by evaluating primary tumor specimens of patients with ESCC are available. PATIENTS AND METHODS: A total of 55 patients with T1 ESCC invading as deep as the submucosal layer who underwent curative esophagectomy were examined. We investigated the significance of the immunohistochemical staining of Vascular endothelial growth factor-C (VEGF-C) and E-cadherin in the primary tumor and Tumor budding for prediction of nodal metastasis. RESULTS: Metastasis to the regional lymph nodes was observed in 26 cases (47.3%) in this setting. VEGF-C expression and reduced E-Cadherin expression in the primary tumor was observed in 32 (58.1%) and 38 cases (69.1%), respectively. High-grade tumor budding was observed in 29 cases (52.7%). E cadherin expression and tumor budding were closely correlated with nodal metastasis (p=0.04 and <0.01 respectively), whereas VEGF-C expression tended to correlate with lymph node metastasis (p=0.06). In addition, high-grade tumor budding was significantly correlated (p<0.01) with reduced E-cadherin expression. The accuracy of tumor budding and E-cadherin expression for nodal metastasis were 67.3% and 65.4% respectively, comparable with the one of lymphatic involvement (63%). Tumor budding (p<0.01), but not E-cadherin and VEGF-C expression, was significantly correlated with poor survival. CONCLUSION: After the endoscopic treatment, additional therapy, such as surgery or chemoradiotherapy, may be required if reduced E-cadherin expression and high-grade tumor budding are observed in primary tumor specimen. PMID- 24222147 TI - Meta-analysis of laparoscopic and open surgery for gastric gastrointestinal stromal tumor. AB - AIM: A meta-analysis was conducted to evaluate and compare the short- and long term outcomes of laparoscopic and conventional open surgery for gastric gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and the Cochrane Controlled Trial Register for relevant articles published between 2000 and July 2013 by using the search terms "laparoscopic", "laparoscopy-assisted", "surgery", "gastrointestinal tumor", "GIST" and "gastric". RESULTS: We identified 12 articles reporting results that compared laparoscopic surgery with open surgery for gastric GISTs. Our meta-analysis included 644 patients with GISTs; 312 had undergone laparoscopic surgery, and 332 had undergone open surgery. In the short-term period, 14 outcome variables were examined. In the long-term period, six oncological variables were analyzed. Laparoscopic surgery for gastric GIST was associated with a reduction in intraoperative blood loss, shorter period to flatus, earlier resumption of oral intake, and shorter duration of hospital stay over the short-term, and with a significantly lower rate of overall recurrence, metastatic recurrence and local recurrence in the long-term compared to open surgery. CONCLUSION: Laparoscopic surgery may be an acceptable surgical treatment option compared to open surgery for gastric GIST. PMID- 24222148 TI - Management of adverse events in patients with metastatic renal cell carcinoma treated with sunitinib and clinical outcomes. AB - Patients with progressive renal cell carcinoma who undergo sunitinib treatment, experience many adverse events (AEs), including thrombopenia and hypertension. Dose reduction or treatment discontinuation due to AEs makes it difficult to control the clinical condition. Therefore, patients' understanding regarding the basics of blood pressure (BP) measurement and how to deal with each AE are particularly important. Here we report whether or not pharmacist instructions help in order to increase patients' awareness of early AE management results in an improvement of treatment outcomes. The present study included 15 patients who were administered sunitinib. From the start of sunitinib treatment, pharmacists continuously provided drug administration guidance to the patients and confirmed their awareness and knowledge regarding AEs, symptom management, and drug adherence. The relative dose intensity (RDI) of 15 patients from week 1 to 24 after sunitinib treatment was calculated. Pharmaceutical interventions significantly improved patients' understanding of BP measurements and reference values, etc. Although the RDI was 67.3%-78.7%, there were no cases of discontinuation of administration or reduction of the dose caused by e.g. hypertension, hand and foot syndrome (HFS) and stomatitis. Pharmaceutical interventions improved patients' awareness of the management of AEs and adherence to sunitinib therapy. As a result, a high RDI was maintained, which may lead to prolonged survival. Therefore, our results suggest that early AE management provided by pharmacists is particularly important to assure the safety and efficacy of sunitinib therapy. PMID- 24222149 TI - C-reactive protein is a negative independent factor in patients with stage IV colorectal cancer undergoing oxaliplatin-based chemotherapy. AB - BACKGROUND/AIM: To determine the clinical significance of C-reactive protein (CRP) concentration in patients with stage IV colorectal cancer (CRC) undergoing oxaliplatin-based chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed the medical charts of 112 patients with stage IV CRC who had received modified FOLFOX6 (5-fluorouracil, oxaliplatin, leucovorin) between January 2006, and December 2010 and used Cox's proportional hazard model to determine for independent prognostic factors of survival. We generated receiver operating characteristics (ROC) curves to determine the optimal cut-off for the discrimination of the duration of survival by CRP concentration. RESULTS: According to the multivariate analysis, increased CRP concentration (p=0.04) and non-curative surgery (p<0.01) were independent unfavorable factors for survival, and the optimal cut-off CRP concentration according to dichotomized duration of survival (3-24 months) ranged from 0.8 to 1.2 mg/dl. CONCLUSION: Pre-chemotherapy CRP concentrations may be useful for predicting survival of patients with stage IV CRC. PMID- 24222150 TI - Clinical outcomes after first-line EGFR inhibitor treatment for patients with NSCLC, EGFR mutation, and poor performance status. AB - BACKGROUND: The phase II NEJ001 trial suggested that gefitinib was active against advanced non-small cell lung cancer (NSCLC) even in patients with poor performance status (PS). Clinical response among the patients harboring epidermal growth factor receptor (EGFR) mutation with poor PS is fair; however, gefitinib does not have as much continued efficacy as in patients with good PS. This study has retrospectively investigated the clinical outcomes of gefitinib treated patients with advanced NSCLC, EGFR mutations, and poor PS. PATIENTS AND METHODS: A total of 208 patients with advanced NSCLC and poor PS treated with gefitinib from 2004 to 2013 were retrospectively evaluated. Outcomes were studied after stratification for gender, smoking status, histological subtype, and EGFR mutation status. RESULTS: Fifty-two patients (25.0%) with advanced NSCLC, EGFR mutation, and poor PS were treated with gefitinib. The overall response rate was 65.4%. The median progression-free survival, median survival time, and one-year survival rate was 6.6 months, 19.6 months, and 62.9%, respectively. Death due to interstitial lung disease occurred in 11.5% of the patient population. In multivariate analysis, a PS of 4 was independently associated with poor outcomes (hazard ratio=10.5; 95% Confidence interval=1.92-50.19; p=0.0091). CONCLUSION: Patients with advanced NSCLC, EGFR mutation, and poor PS have poor outcomes in response to gefitinib. However, the indication of gefitinib for such patients will not be changed in clinical practice and oncologists should treat these patients with more careful follow-up since for those with poor PS, therapy may be more toxic than for patients with good PS. PMID- 24222151 TI - C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery. AB - BACKGROUND: The clinical significance of the systemic inflammatory response (SIR) in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (CRT), to the best of our knowledge, has not been thus far investigated. PATIENTS AND METHODS: The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and C-Reactive protein (CRP) levels for 84 patients with rectal cancer undergoing CRT were available as indicators of SIR status. The impact of SIR status on the prognosis of these patients was assessed. RESULTS: Elevated NLR, CRP, carcinoembryonic antigen (CEA) and pathological TNM stage III [ypN(+)] were identified as significant prognostic factors for poor overall survival (OS), with CRP and ypN(+) being validated as independent predictors of OS. Elevated CRP and CEA levels were significant predictive factors for poor disease-free survival (DFS), and an elevated CRP level was identified as the only independent predictive factor for DFS. In addition, an elevated CRP level predicted for poorer OS and DFS in patients with pathological TNM stage I-II [ypN(-)]. CONCLUSION: CRP is a promising predictor of recurrence and prognosis in patients with rectal cancer treated by CRT. PMID- 24222152 TI - A new beta-tricalcium phosphate with uniform triple superporous structure as a filling material after curettage of bone tumor. AB - BACKGROUND: A new beta-tricalcium phosphate with uniform triple superpore structure, SuperPore((r)) (HOYA, Tokyo, Japan), has been in clinical use since 2010. As far as we are aware of, there have been no reported clinical studies using this material. We report on the first clinical cases of benign bone tumor filled with SuperPore((r)). PATIENTS AND METHODS: We retrospectively evaluated the results for 34 benign bone tumors treated by curettage followed by implantation of the highly purified beta-tricalcium phosphates Osferion((r)) (Olympus, Tokyo, Japan) or SuperPore((r)). RESULTS: After a mean follow-up of 12 months, none of the patients experienced local recurrence of the tumor or any adverse effects from the filling materials. Radiographically, complete resorption of the material and bone remodeling were achieved in 32 cases. In 17 selected cases with a small bone tumor, the mean period for complete resorption of the filling material was 21 weeks in the Osferion((r)) group and 15 weeks in the SuperPore((r)) group, with the latter showing a trend for better outcomes. CONCLUSION: SuperPore((r)) is a safe and reliable filling substitute for defects following curettage of small bone tumors. Both SuperPore((r)) and Osferion((r)) gave satisfactory results with good biocompatibility and fast resorption characteristics. PMID- 24222153 TI - Clinical significance of erlotinib monotherapy for gefitinib-resistant non-small cell lung cancer with EGFR mutations. AB - BACKGROUND: The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib is difficult to be accurately assessed in patients with non-small cell lung cancer (NSCLC) because it is commonly employed after failure of another EGFR-TKI, gefitinib. PATIENTS AND METHODS: Medical records from 104 patients with NSCLC treated with erlotinib were retrospectively reviewed. RESULTS: There were no significant differences in erlotinib efficacy between EGFR-mutated NSCLC with gefitinib resistance and NSCLC with wild-type EGFR. A therapeutic response of disease control (DC) and the onset of skin rash prolonged the progression-free survival (PFS), whereas the onset of interstitial lung disease shortened both PFS and overall survival (OS). The DC group also experienced prolonged OS. CONCLUSION: Erlotinib may be a therapeutic option for EGFR-mutated NSCLC with gefitinib resistance, as well as for NSCLC with wild-type EGFR. Therapeutic response of DC and the onset of the described adverse events may be practical predictors of survival in erlotinib treatment. PMID- 24222154 TI - The E-Cadherin expression vs. tumor cell proliferation paradox in endometrial cancer. AB - BACKGROUND: E-Cadherin is a putative marker of good prognosis in endometrial cancer. Paradoxically, in a previous study of endometrial carcinoma we found that E-Cadherin is significantly co-expressed with molecular markers of proliferation, usually associated with a worse prognosis in most tumor types. PATIENTS AND METHODS: The expression of estrogen (ER) and progesterone receptors (PR), Ki67, Human Epidermal Growth Factor Receptor 2 (HER-2, c-ERB-B2), p53 and E-Cadherin was studied by means of immunohistochemistry in 126 endometrial carcinoma samples. The results were correlated with patient survival and included in a multivariate model, in order to identify factors independently associated with the patient outcome. RESULTS: E-Cadherin overexpression was associated with a significantly better overall survival in the whole group of patients with endometrial carcinoma (p=0.012), as well as in the group of patients exclusively harboring endometrioid tumors (p=0.004). In a restricted multivariate model, only tumor stage and E-Cadherin expression retained their independent prognostic power, both for the whole group of tumors (p=0.04), as well as for the subgroup of endometrioid carcinomas (p=0.05). CONCLUSION: E-Cadherin is an independent predictor of survival in endometrial carcinoma, regardless of histological variety. Proliferation, on the other hand, does not seem to play a prominent role in this same context. This may explain why E-Cadherin retains its prognostic power, despite being significantly co-expressed with all tested molecular proliferation markers. PMID- 24222155 TI - Changing trends in long-term outcomes after hepatic resection for hepatocellular carcinoma: A 30-year, single-center experience. AB - BACKGROUND: The aim of this study was to characterize changes in outcome following hepatectomy for hepatocellular carcinoma (HCC) over a 30-year period. PATIENTS AND METHODS: The clinical records of 372 patients who underwent a macroscopic curative hepatectomy for treatment of HCC between 1980 and 2009 were retrospectively examined. Patients were divided into two groups: an early group (1980-2000) and a late group (2001-2009). The relationship between the chronological treatment period and the surgical outcomes was investigated. RESULTS: The disease-free survival (DFS) was comparable between the early and late groups (at 5 years: 30.3% vs. 31.2%, p=0.526), however, the overall survival (OS) of the late group was significantly better than the one of the early group (at 5 years: 80.1% vs. 50.4%, p<0.001), with this being an independent prognostic factor. Among the 148 patients who underwent transarterial chemoembolization (TACE) for initial hepatic recurrence, the OS after initial recurrence of the late group was significantly better than that of the early group (p=0.002). The OS after initial recurrence was significantly better in patients who underwent repeat hepatectomy than in those who underwent TACE (p=0.044). CONCLUSION: The results of hepatectomy for HCC have improved over time by use of various combination therapies after initial HCC recurrence. A repeat hepatectomy may be an acceptable treatment option for HCC recurrence in selected patients. PMID- 24222156 TI - Non-randomized comparison between irinotecan plus mitomycin C and irinotecan alone in patients with advanced gastric cancer refractory to fluoropyrimidine and platinum. AB - BACKGROUND: Irinotecan alone and plus mitomycin C have been proven to be effective as second-line chemotherapy for advanced gastric cancer. The objective of the present study was to compare the efficacy and safety of irinotecan alone (CA) and with mitomycin C (CM) in clinical practice. PATIENTS AND METHODS: Between November 2006 and December 2011, 46 patients with advanced gastric cancer refractory to fluoropyrimidine and platinum were treated with CM (n=22) or CA (n=24). RESULTS: Baseline characteristics of the patients were similar in the two treatment groups, with the exception of the sex ratio. The median progression free survival was 3.9 months in the CM arm and 3.7 months in the CA arm (p=0.25), and the median overall survival was 9.6 and 8.7 months (p=0.36), respectively. The overall response rate was 18% in the CA arm and 9% in the CM arm (p=0.38). Grade 3/4 neutropenia (45% vs. 25%), anemia (36% vs. 4%), febrile neutropenia (14% vs. 8%), anorexia (14% vs. 8%) tended to be higher in the CM arm than in the CA arm. CONCLUSION: Although the efficacy of CM and CA for advanced gastric cancer refractory to fluoropyrimidine and platinum was not significantly different, CM tended to lead to greater incidence of adverse events in clinical practice. PMID- 24222157 TI - Clinical significance of total colonoscopy for screening of colon lesions in patients with esophageal cancer. AB - AIM: The objective of the present study was to evaluate the significance of pre treatment screening for patients with esophageal cancer. PATIENTS AND METHODS: A retrospective evaluation of the clinical significance of total colonoscopy in 136 patients with primary esophageal cancer was performed. RESULTS: Twenty-three patients (16.9%) had diverticula, and five (3.7%) had colon cancer. Benign polyps were present in 57 patients (41.9%); 37 of these patients underwent endoscopic treatment, one underwent surgery (esophagectomy). Twenty-seven out of 32 patients (84.4%) who underwent histopathological studies had tubular adenoma. Significant associations were found between presence of colorectal lesions and body weight, body-mass index (p<0.001), Brinkman index (p<0.001), and the Sake index (p<0.05). CONCLUSION: Screening for colorectal lesions using total colonoscopy is important in patients with esophageal cancer, especially for those with a high body-mass index, and those who smoke or drink heavily. PMID- 24222158 TI - Early-onset brain metastases in a breast cancer patient after pathological complete response to neoadjuvant chemotherapy. AB - Breast cancer patients who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) usually have a favourable prognosis. We report on a patient with early metastases to the brain after achieving pCR. The primary tumour was 7.0 cm in diameter with axillary lymph node metastases, hormone receptor-negative, human epidermal growth factor receptor-2-positive (3+), and histological grade 2 with 60% of cells positive for Ki-67. The patient underwent NAC followed by surgery, and achieved pCR. Five months after surgery, during adjuvant treatment with trastuzumab, she developed headache and dizziness. Brain imaging revealed multiple metastatic brain tumours. She received whole-brain radiotherapy followed by lapatinib and capecitabine therapy. At 7 months after surgery, she remains alive with a persistent mild headache. Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR. PMID- 24222159 TI - Concurrent chemoradiotherapy for non-bulky stage IB/II cervical cancer without pelvic node enlargement. AB - BACKGROUND: Concurrent chemoradiotherapy (CCRT) has not been extensively studied in patients with small cervical cancer tumors with no pelvic node enlargement. PATIENTS AND METHODS: We retrospectively analyzed 55 patients with stage IB1-IIB cervical cancer and tumors of <=40 mm with no pelvic node enlargement treated with radiotherapy (RT)-alone. RESULTS: Cancer recurred in seven patients. Patient age (<=63 years) was identified as an independent factor for better disease-free survival (DFS) (p=0.027), and tumor size (>=25 mm) had a tendency to correlate with reduced locoregional DFS (p=0.089) by the Cox hazard model. Among patients aged 63 years or less, cancer recurred in five out of 18 patients with tumors of >=25 mm, but in only one of 10 patients with tumors of <=24 mm. CONCLUSION: In patients with stage IB1-IIB cervical cancer and small tumors with no node enlargement, CCRT may provide a better disease control for the group aged 63 years or less and with tumor size of 25 mm or more. PMID- 24222160 TI - High-throughput molecular genotyping for small biopsy samples in advanced non small cell lung cancer patients. AB - BACKGROUND: Despite the key role of mutational analysis in targeted therapy, the difficulty in acquisition of adequate tumor tissues for molecular genotyping in advanced non-small cell lung cancer (NSCLC) has led to the need for a fast and efficient method for detecting genetic alterations for targeted therapy. PATIENTS AND METHODS: We analyzed tissue specimens of advanced NSCLC. A mass spectrometry based assay was used to investigate 471 oncogenic mutations. All tumor specimens were prepared from fresh-frozen tissues. RESULTS: In total, there were 59 hotspot mutations in 67% of the entire patient group (41 out of 61 patients). The most frequent mutation was in TP53 (n=24, 39.3%), followed by EFGR (n=19, 31.1%). Others included MLH1, KRAS, PIK3CA, ERBB2, ABL1 and HRAS. CONCLUSION: Our results suggest that molecular genotyping using high-throughput technology such as OncoMap v4 is feasible, even with small biopsied specimens from patients with advanced NSCLC. PMID- 24222161 TI - Lymphadenectomy alone is a feasible option in managing incidentally-detected early-stage cervical cancer after simple hysterectomy without intermediate-risk factors: An application of the concept of less radical surgery. AB - AIM: To assess the feasibility of less radical surgery in patients with incidentally-detected cervical cancer at simple hysterectomy. PATIENTS AND METHODS: High-risk factors (HFs) were evaluated in 104 patients who underwent radical hysterectomy and lymphadenectomy for the treatment of stage IA1-IB1 cervical cancer according to intermediate-risk factors (IFs). RESULTS: Thirty three patients without IFs had no HFs. As the number of IFs increased, the number of HFs increased (p=0.009). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for parametrial involvement (hazard ratio, 31.3; 95% confidence interval, 1.6-599.4; p=0.022). An absence of IFs was associated with a longer progression-free survival than the presence of IFs in the subgroup analysis of favorable histologies (p=0.044). CONCLUSION: HFs could be excluded in stage IA1-IB1 cervical cancer without IFs. Omitting parametrectomy seems a feasible option for selected patients with incidentally detected early-stage cervical cancer at simple hysterectomy, without IFs. PMID- 24222162 TI - Histological inflammatory cell infiltration is associated with the number of lymph nodes retrieved in colorectal cancer. AB - BACKGROUND: Antitumor immune response is suggested to be a factor affecting the number of nodes retrieved after colorectal cancer surgery. The purpose of this study was to evaluate the correlation of antitumor immune response with the number of retrieved nodes. PATIENTS AND METHODS: Patients with colorectal cancer (n=63, TNM stage II and III) were enrolled. Inflammatory cell infiltration (ICI) was assessed on hematoxylin and eosin staining and T-cell markers (CD3, CD8, CD45RO) were evaluated using immunohistochemical methods. RESULTS: On univariate analysis, high ICI, CD3 and CD8 expression were associated with a greater number of nodes being retrieved. On multivariate analysis, tumors of the right colon (p=0.01) and high ICI (p=0.04) were independent predictors of a greater retrieval of nodes. TNM stage III tumor with low ICI was associated with reduced cancer specific survival (p=0.02). CONCLUSION: ICI influences the number of nodes retrieved and affects survival of patients with stage III disease. Antitumor immune response may be an underlying factor determining the number of nodes retrieved after surgery for colorectal cancer. PMID- 24222163 TI - Ethnic variation in toxicity and outcome of adjuvant chemoradiation for gastric cancer in Israel. AB - BACKGROUND: Data on differences in toxicity and efficacy of chemotherapy and radiotherapy among different ethnic groups is limited. We evaluated differences in toxicity, tolerability and clinical outcome of Ashkenazi and non-Ashkenazi Jews receiving postoperative chemoradiation for locally advanced gastric cancer (LAGC). PATIENTS AND METHODS: Between 6/2000-12/2007, 84 Ashkenazi patients and 60 non-Ashkenazi patients underwent chemoradiation following resection of LAGC (INT-116 trial). RESULTS: Patients' and tumor characteristics were comparable. Ashkenazi patients experienced significantly higher rates of fatigue, anorexia, and grade 3-4 dysphagia, as well as a trend for a higher rate of diarrhea. The incidence of other toxicities, dose adjustments of chemotherapy and radiotherapy and patient prognosis did not differ. CONCLUSION: This study shows higher rates of various toxicities among Ashkenazi patients receiving postoperative chemoradiation for LAGC compared to non-Ashkenazi patients. To our knowledge, this is the first study comparing treatment toxicity, tolerability and outcome between these two groups. PMID- 24222164 TI - A9 region in EPHB2 mutation is frequent in tumors with microsatellite instability. Analysis of prognosis. AB - AIM: The aim of the present study was to determine the relation of EPH tyrosine kinase receptor B2 (EPHB2) A9 region mutation and microsatellite instability (MSI); and to analyze their influence in prognosis of patients with sporadic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 481 patients with CRC were examined. MSI (NCI criteria) and EPHB2 were analyzed using PCR and fragment analysis software. RESULTS: EPHB2 mutation was detected in 3.1% of patients. Mutation of EPHB2 was associated with location and with MSI status. We considered low instability (L-MSI) when only one marker showed instability, high instability (H-MSI) when two or more markers were positive and microsatelllite stable (MSS) when no instability was detected. The stratified analysis of overall survival (OS) and disease-free survival (DFS) in MSI according to EPHB2 status revealed no statistically significant differences. However, the risk of recurrence of H-MSI tumors with EPHB2 mutation carriers was 3.6-times higher than in non-mutation carriers. CONCLUSION: The frequency of EPHB2 mutation is higher in patients with H-MSI than MSS tumors. Promising results were found regarding the prognostic influence of EPHB2 in H-MSI. PMID- 24222165 TI - Effect of hospital volume on long-term outcomes of laparoscopic gastrectomy for clinical stage I gastric cancer. AB - BACKGROUND: This study aimed to examine the effect of hospital volume on long term outcomes of patients who underwent laparoscopic gastrectomy for clinical stage I gastric cancer. PATIENTS AND METHODS: A total of 420 patients with clinical stage I gastric cancer who underwent laparoscopic gastrectomy at our university hospital (high-volume group) and affiliated hospitals (low-volume group) were included in this study. Overall survival (OS) and cause-specific survival (CSS) rates were analyzed. RESULTS: No significant differences were observed in the number of lymph nodes retrieved (29.9 vs. 27.7, p=0.21) and CSS between the high- and low-volume groups (p=0.92), although the OS rate in the low volume group was significantly less than that in the high-volume group (p=0.045). CONCLUSION: These results indicate no clinical impact of hospital volume on prognosis of patients who underwent laparoscopic gastrectomy for clinical stage I gastric cancer when performed by surgeons with sufficient experience in open gastrectomy. PMID- 24222166 TI - Predictors of long-term survival in hepatocellular carcinomas: A longitudinal follow-up of 108 patients with small tumors. AB - AIM: Locoregional treatment [including percutaneous ethanol injection (PEI) therapy and transcatheter arterial chemoembolization (TACE)] provides an alternative treatment for early-diagnosed hepatocellular carcinoma (HCC). However, the long-term survival of patients after locoregional treatments remains unclear. PATIENTS AND METHODS: A total of 108 patients with small HCC not indicated for surgical hepatic resection were recruited between 1991 and 1999. All patients received first treatment with PEI therapy alone or combined with TACE. We followed-up these patients until the end of 2007. Clinical attributes and biological markers in association with long-term survival were collected. Significant predictors were identified by using proportional hazards regression model. RESULTS: The overall 1-, 3-, 5-, and 10-year cumulative survival of patients with HCC (<5 cm) were 88.8%, 59.4%, 29.4%, and 12.3%, respectively. Child-Pugh status, type of tumor (solitary or multiple), levels of pre-treatment aspartate aminotransferase (AST), and treatment modality were significantly associated with long-term survival after adjustment for age and gender. Child Pugh B (hazard ration, HR=1.98, 95% confidence interval, CI=1.08-3.60) and higher level of pre-treatment AST (HR=1.91, 95% CI=1.18-3.08) were the two most significant predictors for risk of death from HCC-after adjusting for treatment modality and type of tumor. CONCLUSION: Child-Pugh score and AST level were demonstrated as the two major predictors for long-term survival in patients with small HCC not indicated for surgical treatment who underwent PEI-alone or combined with TACE. Clinical weights from Child-Pugh score and AST level are very informative for risk stratification and clinical surveillance of patients with small HCC treated by PEI-alone or combined with TACE. PMID- 24222167 TI - A survey of c-MET expression and amplification in 287 patients with hepatocellular carcinoma. AB - BACKGROUND: c-N-Methyl-N'-nitro-N-nitroso-guanidine HOS transforming gene (c-MET) is a new potential drug target for treatment of patients with hepatocellular carcinoma (HCC), and a recent study of a c-MET inhibitor in such patients has shown promising results. In the present study, we investigated the incidence of c MET overexpression and its prognostic impact. MATERIALS AND METHODS: Tumor tissue microarrays were used to detect the expression of c-MET in samples from 287 patients with HCC who underwent surgical resection at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features of HCC, and investigated recurrence-free survival (RFS) and HCC-specific survival according to the level of c-MET expression. Additionally, we explored the correlation between c-MET protein overexpression, and MET mRNA expression and copy number variation. RESULTS: Most patients in the present study were male (n=297, 82.6%), with Child-Pugh class A liver function (n=286, 99.7%) and hepatitis B viral infection (n=217, 75.6%). c-MET overexpression was observed in 80 patients (27.9%), and was not associated with Edmondson grade, tumor size, microvascular invasion, major portal vein invasion or stage. In addition, c-MET expression levels did not affect RFS or HCC-specific survival. c-MET expression was weakly correlated with c-MET copy number variation (r=0.255, p<0.001), but more than half of all patients with c-MET overexpression had a neutral c-MET copy number. c-MET protein expression was very weakly but significantly positively correlated with its mRNA expression (r=0.199, p=0.002). CONCLUSION: c-MET overexpression did not have any prognostic impact on recurrence or survival of patients with HCC undergoing surgical resection. However, 27.9% of patients who had c-MET overexpression could be considered candidates for treatment with c-MET inhibitor. PMID- 24222168 TI - Chemoradiation as a definitive treatment for cervical lymph node metastases from unknown primary cancer. AB - AIM: To assess the treatment outcomes of chemoradiation for cervical lymph node metastases from an unknown primary site (CUP), and to identify for prognostic factors. PATIENTS AND METHODS: Thirty patients diagnosed as having CUP, and receiving chemoradiation as a definitive treatment were included in the analysis. Locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were estimated, and the factors affecting treatment outcomes were analyzed. RESULTS: After a median follow-up period of 25 months for surviving patients, the two- and five-year LRC, DFS, and OS rates were 56%/45%, 46%/36%, and 69%/52%, respectively. On univariate analysis, lower performance status (PS; p=0.001), and limitation of disease to level 2 or 3 lymph nodes (p=0.009) were significantly associated with better DFS. Low PS (p=0.002) was significantly associated with better LRC. No late toxicity of grade 3 or greater was observed. CONCLUSION: Definitive chemoradiation for CUP was well-tolerated, with improvement of DFS/LRC for those with good PS and disease limited to level 2 or 3 lymph nodes. PMID- 24222169 TI - Outcome analysis of (18)F-fluorodeoxyglucose positron-emission tomography in patients with lung cancer after partial volume correction. AB - BACKGROUND: This study aimed to evaluate the necessity for the partial volume effect (PVE) correction of the maximum standardized uptake value (SUVmax) in (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET) for predicting outcome in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 191 patients, with tumor diameters ranging from 10-37 mm, underwent pre-operative FDG-PET and curative resection. The SUVmax (Pre-SUV) of the primary tumor was corrected (Cor-SUV) using a recovery coefficient curve based on phantom experiments. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of the patients with high Pre-SUVs were lower than those with low Pre-SUVs (p<0.001 and p=0.002, respectively). The 5-year OS and DFS of patients with high Cor-SUVs were significantly lower than those with low Cor-SUVs (p<0.001 and p=0.005, respectively). CONCLUSION: Even without PVE correction, SUVmax was able to predict for outcome in patients with NSCLC. PMID- 24222170 TI - Aberrant methylation of the Ras-related associated with diabetes gene in human primary esophageal cancer. AB - BACKGROUND/AIM: Ras-related associated with diabetes (RRAD), a member of the Ras related GTPase superfamily, is frequently methylated in several human cancers, though its methylation profile remains unclear in esophageal cancer. MATERIALS AND METHODS: We examined RRAD promoter hypermethylation using real-time quantitative methylation-specific PCR in 229 primary human esophageal tissues of contrasting histological types. RESULTS: RRAD hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) from esophageal adenocarcinoma (EAC) or normal esophagus (NE) (p<0.01 and p<0.01, respectively). RRAD normalized methylation values were significantly higher in ESCC (0.0242) than in NE (0.0057, p<0.05) or EAC (0.0139, p<0.01). RRAD hypermethylation frequency was also significantly higher in ESCC (23.1%) than in NE (0%, p<0.05) or EAC (5.4%, p<0.05). CONCLUSION: Promoter hypermethylation of RRAD is a frequent, tissue-specific event in ESCC, and is uncommon in EAC. The aberrant methylation of RRAD may be involved in the pathogenesis of a subset of ESCC, but not in EAC. PMID- 24222171 TI - Testis-sparing surgery for the conservative management of small testicular masses: an update. AB - BACKGROUND: Malignant germ cell tumours represent the vast majority of palpable testicular masses, and radical orchiectomy is still considered the standard-of care. Testis-sparing surgery (TSS) could be an alternative to radical orchiectomy in patients diagnosed with small testicular masses (STMs). The aim of this article was to review the current indications and the oncological and functional outcomes of TSS when performed for STMs. MATERIALS AND METHODS: We performed a non-systematic review of literature using the Medline database, including a free text protocol using the terms "testis sparing surgery", "partial orchiectomy", "testis tumour" and "sex cord tumour". Only the articles reporting data on organ sparing surgery for testicular neoplasms were evaluated. RESULTS: No randomized controlled trials comparing TSS with radical orchiectomy have been reported. Indications for TSS are controversial, especially for patients with normal contra lateral testis. For testicular masses of less then 2 cm, TSS seems to be the best treatment option. Frozen-section examination is an essential assessment at the time of TSS, and allows for discrimination of benign from malignant neoplasms. Intermediate- and long-term follow-up results showed no significant risk of local and distant recurrences in the main series reported in literature. CONCLUSION: According to currently available data, TSS is a safe and effective treatment for STMs in selected patients, and bypasses surgical overtreatment, without compromising oncological and functional outcomes. Further studies are needed in order to confirm the oncological safety of this procedure. PMID- 24222174 TI - How do babies know their friends and foes? AB - The study of infant social cognition is the study of how human infants acquire information about people. By examining infants' sensory abilities and the stimulus characteristics of people, research can determine what information is available to infants from their social world. We can then consider what social environments are appropriate for infants of different ages. This paper examines the sociocognitive competencies of human infants during the first 6 months of their lives and asks how these competencies are functional in the daily social ecology of the human infant. Select examples of research with other species are used to illustrate how the adaptive significance of sociocognitive abilities could be more fruitfully explored in studies of human infancy. PMID- 24222175 TI - The early crying paradox : A modest proposal. AB - In contemporary Western societies, infants in the first 3 months cry more than at any other time during their life. Although this crying is believed to function to assure nutrition, protection, and mother-infant interaction thought to be essential for later attachment, it also predisposes to complaints of excessive crying ("colic"), discontinuing breast-feeding, and, in the extreme case, child abuse. A resolution of this apparent paradox is proposed based on evidence that elements of caregiving are important determinants of some aspects of early crying. It is argued that early human crying under caretaking conditions typical in Western societies is characterized by prolonged crying bouts, that it is specifically the length of crying bouts (rather than frequency or pattern) that is affected by caregiving practice, and that prolonged crying bouts are probably not characteristic with caretaking practices typical in non-Western societies and possibly in our evolutionary past. It is suggested that caregiving behaviors may recruit normal physiological functions that potentiate cry bout duration in Western caregiving contexts, but reduce it in others. Frequent, short bouts are sufficient, and probably better suited than long bouts, to promote all the positive and presumably adaptive functions claimed for infant crying. Furthermore, they may have provided a mechanism by which infants could enhance their own fitness. PMID- 24222176 TI - Anorexia nervosa : Levels of causation. AB - Anorexia nervosa remains an enigma among Western cultures. Various causal explanations have been offered, encompassing biological, psychological, and sociocultural models. These explanations, however, focus on the immediate or proximal mechanisms of causation. A more thorough understanding of anorexia nervosa can be achieved by understanding the relationship between these factors and ultimate causation, the level of explanation which deals with individual reproductive fitness. This paper reviews the biological, psychological, sociocultural, and evolutionary models and indicates a necessary synthesis between proximate and ultimate levels of causation in examining the anorexia nervosa puzzle. PMID- 24222177 TI - The exotic and the mundane : Human immunodeficiency virus in Haiti. AB - The HIV/AIDS epidemic in Haiti has often been referred to as a "mystery," and "striking similarities" between patterns of disease in Haiti and in sub-Saharan Africa are often underlined. The occurrence of AIDS in Haitians has also led to the postulation of a number of theories positing a Haitian origin for AIDS and linking the syndrome in Haitians to voodoo. A review of the epidemiological data gathered and published in the early years of the pandemic suggests that these "exotic" theories are not necessary to explain the Haitian epidemic, which is clearly linked not to Africa but to the United States. Patterns of risk identified among many of the first Haitians with AIDS are similar to risk factors identified in North America and Europe (same-sex contact with an HIV-infected individual and blood transfusion). The Haitian epidemicsubsequently came to resemble patterns seen in sub-Saharan Africa, where AIDS is predominantly a heterosexually transmitted disease. Similarly shifting patterns are described for several other Caribbean nations, underlining the importance of a historical analysis of the Caribbean pandemic as well as the necessity to link analysis of local epidemiology of AIDS/HIV to larger considerations of political economy. PMID- 24222178 TI - A traceless directing group for C-H borylation. AB - Not a trace: Borylation of the nitrogen in nitrogen heterocycles or anilines provides a traceless directing group for subsequent catalytic C-H borylation. Selectivities that previously required Boc protection can be achieved; furthermore, the NBpin directing group can be installed and removed in-situ, and product yields are substantially higher. Boc=tert-butoxycarbonyl, pin=pinacolato. PMID- 24222179 TI - Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma. AB - PURPOSE: Although microRNAs (miRNA) show potential as diagnostic biomarkers in cancer, their role as circulating cell-free disease response biomarkers remains unknown. Candidate circulating miRNA biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells and/or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, embedded within a benign microenvironment, the composition of which is distinct from that seen in healthy lymph nodes. EXPERIMENTAL DESIGN: Microarray profiling of more than 1,000 human miRNAs in 14 cHL primary tissues and eight healthy lymph nodes revealed a number of new disease node-associated miRNAs, including miR-494 and miR-1973. Using quantitative real-time PCR (qRT-PCR), we tested the utility of these, as well as previously identified disease node-associated plasma miRNAs (including miR-21 and miR-155), as disease response biomarkers in a prospective cohort of 42 patients with cHL. Blood samples were taken in conjunction with radiologic imaging at fixed time points before, during, and after therapy. Absolute quantification was used so as to facilitate implementation in diagnostic laboratories. RESULTS: Levels of miR-494, miR-1973, and miR-21 were higher in patients than control (n = 20) plasma (P = 0.004, P = 0.007, and P < 0.0001, respectively). MiR-494 and miR-21 associated with Hasenclever scores >=3. Strikingly, all three miRNAs returned to normal at remission (P = 0.0006, P = 0.0002, and P < 0.0001 respectively). However, only miR-494 and miR-1973 reflected interim therapy response with reduction being more pronounced in patients achieving complete versus partial responses (P = 0.043 and P = 0.0012, respectively). CONCLUSION: Our results demonstrate that in patients with cHL, circulating cell-free miRNAs can reflect disease response once therapy has commenced. PMID- 24222180 TI - Survival impact of surgical resection of primary tumor in patients with stage IV colorectal cancer: results from a large population-based cohort study. AB - BACKGROUND: Currently, there is very low-quality evidence available regarding benefit of surgical resection of the primary tumor (SRPT), in patients with stage IV colorectal cancer (CRC). In the absence of randomization, the reported benefit may reflect selection of younger and healthier patients with good performance status. A large population-based cohort study was undertaken to determine the survival benefit of SRPT in advanced CRC by eliminating various biases reported in the literature. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan, Canada. Survival was estimated by using the Kaplan-Meier method. Survival distribution was compared by log-rank test. Cox proportional multivariate regression analysis was performed to determine survival benefit of SRPT by controlling other prognostic variables. RESULTS: A total of 1378 eligible patients were identified. Their median age was 70 years (range, 22-98 years) and male:female ratio was 1.3:1; 944 (68.5%) of them underwent SRPT. Among 1378 patients, 42.3% received chemotherapy and 19.1% received second-generation therapy. Patients who underwent SRPT and received chemotherapy had median overall survival of 18.3 months (95% confidence interval [CI] = 16.6-20 months) compared with 8.4 months (95% CI = 7.1-9.7 months) if they were treated with chemotherapy alone (P < .0001). Cox proportional analysis revealed that use of chemotherapy (hazard ratio [HR] = 0.47, 95% CI = 0.41-0.54), SRPT (HR = 0.49, 95% CI = 0.41 0.58), second-line chemotherapy (HR = 0.47, 95% CI = 0.45-0.64), and metastasectomy (HR = 0.54, 95% CI = 0.45-0.64) were correlated with superior survival. CONCLUSIONS: SRPT improves survival in patients with stage IV CRC, independent of other prognostic variables including age, performance status, comorbid illness and chemotherapy. PMID- 24222181 TI - Beyond the tangent point: gaze targets in naturalistic driving. AB - Moving in natural environments is guided by looking where you are going. When entering a bend, car drivers direct their gaze toward the inside of the curve, in the region of the curve apex. This behavior has been analyzed in terms of both "tangent point models," which posit that drivers are looking at the tangent point (TP), and "future path models," which posit that drivers are visually targeting a point on the desired trajectory or future path (FP). This issue remains unresolved, partly due to the challenge of representing the changing visual projection of the trajectory into the driver's field of view. This paper reports a study of naturalistic driving, in which the FP in the field of view is explicitly modeled, and the TP and reference points on the FP are simultaneously analyzed as potential gaze targets. We argue that traditional area-of-interest methods commonly interpreted as supporting the TP hypothesis are problematic when the interest is contrasting multiple gaze targets. This prompts a critical reassessment of the empirical case for the ubiquity of looking at the TP and the generality of the TP hypothesis as an account of where people look when they steer. As a basis for representing driver gaze behavior, the FP is an equally valid point of departure. There are no overwhelming theoretical or empirical reasons for favoring the TP models over the FP models. PMID- 24222182 TI - A synchronous surround increases the motion strength gain of motion. AB - Coherent motion detection is greatly enhanced by the synchronous presentation of a static surround (Linares, Motoyoshi, & Nishida, 2012). To further understand this contextual enhancement, here we measured the sensitivity to discriminate motion strength for several pedestal strengths with and without a surround. We found that the surround improved discrimination of low and medium motion strengths, but did not improve or even impaired discrimination of high motion strengths. We used motion strength discriminability to estimate the perceptual response function assuming additive noise and found that the surround increased the motion strength gain, rather than the response gain. Given that eye and body movements continuously introduce transients in the retinal image, it is possible that this strength gain occurs in natural vision. PMID- 24222183 TI - EEG precursors of detected and missed targets during free-viewing search. AB - When scanning a scene, the target of our search may be in plain sight and yet remain unperceived. Conversely, at other times the target may be perceived in the periphery prior to fixation. There is ample behavioral and neurophysiological evidence to suggest that in some constrained visual-search tasks, targets are detected prior to fixational eye movements. However, limited human data are available during unconstrained search to determine the time course of detection, the brain areas involved, and the neural correlates of failures to detect a foveated target. Here, we recorded and analyzed electroencephalographic (EEG) activity during free-viewing visual search, varying the task difficulty to compare neural signatures for detected and unreported ("missed") targets. When carefully controlled to remove eye-movement-related potentials, saccade-locked EEG shows that: (a) "Easy" targets may be detected as early as 150 ms prior to foveation, as indicated by a premotor potential associated with a button response; (b) object-discriminating occipital activity emerges during the saccade to target; and (c) success and failures to detect a target are accompanied by a modulation in alpha-band power over fronto-central areas as well as altered saccade dynamics. Taken together, these data suggest that target detection during free viewing can begin prior to and continue during a saccade, with failure or success in reporting a target possibly resulting from inhibition or activation of fronto-central processing areas associated with saccade control. PMID- 24222184 TI - The composite effect for inverted faces is reliable at large sample sizes and requires the basic face configuration. AB - The absence of the face composite effect (FCE) for inverted faces is often considered evidence that holistic processing operates only on upright faces. However, such absence might be explained by power issues: Most studies that have failed to find the inverted FCE tested 24 participants or less. Here we find that the inverted FCE exists reliably when we tested at least 60 participants. The inverted FCE was ~ 18% the size of the upright FCE, and it was unaffected by testing order: It did not matter whether participants did the upright condition first (Experiment 1, n = 64) or the inverted condition first (Experiment 2, n = 68). The effect also remained when upright and inverted trials were mixed (Experiment 3, n = 60). An individual differences analysis found a modest positive correlation between inverted and upright FCE, suggesting partially shared mechanisms. A critical control experiment demonstrates that the inverted FCE cannot be explained by visuospatial attention or other generic accounts because the effect disappeared when the basic face configuration was disrupted (Experiment 4, n = 50). Our study shows that the inverted FCE is a reliable effect that requires an intact face configuration, consistent with the notion that some holistic processing also operates on inverted faces. PMID- 24222185 TI - Prognostic impact of NDRG2 and NDRG3 in prostate cancer patients undergoing radical prostatectomy. AB - AIM: To investigate the clinicopathologic significance of NDRG2 and NDRG3, and their involvement in recurrence-free survival (RFS) and overall survival (OS) of prostate cancer (PCa). METHODS: NDRG2 and NDRG3 expression in 206 pairs of primary PCa and corresponding noncancerous prostate tissue samples from the same specimens were detected by immunohistochemistry. The association of NDRG2 and NDRG3 expression with the clinicopathologic features and with the prognosis of PCa was subsequently assessed. RESULTS: In PCa tissues, NDRG2 expression was significantly downregulated, while NDRG3 expression was significantly upregulated (both P<0.001), compared with those in corresponding noncancerous prostate tissues. In addition, the downregulation of NDRG2 in PCa tissues was significantly correlated with advanced pathological stage (P=0.001), positive metastatic status (P=0.001) and high Gleason score (P=0.003), while the upregulation of NDRG3 in PCa tissues was significantly correlated with advanced pathological stage (P=0.006), positive metastatic status (P=0.001) and lymph node status (P=0.002). Furthermore, multivariate survival analysis showed low NDRG2 and high NDRG3 immunoreactivities were both significantly associated with short RFS and short OS in PCa independently of routine clinicopathological predictors. CONCLUSION: Our data offer convincing evidence for the first time that the aberrant expression of NDRG2 and NDRG3 may contribute to the malignant progression of PCa. More importantly, both the downregulation of NDRG2 and the upregulation of NDRG3 may be efficient prognostic indicators for PCa. PMID- 24222186 TI - Reliability of laryngostroboscopic evaluation on lesion size and glottal configuration: a revisit. AB - OBJECTIVES/HYPOTHESIS: This study investigated the inter-rater and intrarater reliability of four basic visual perceptual parameters (lesion size rating and glottal configuration) in laryngostroboscopic evaluation. STUDY DESIGN: Cohort Study. METHODS: Two hundred fifty-five laryngostroboscopic video samples were evaluated by three raters on four measurements: 1) mass lesion size rating, 2) amplitude of vocal fold vibration, 3) supraglottic activity, and 4) shape of the glottal closure using the modified Stroboscopy Examination Rating Form. RESULTS: Good inter- and intrarater reliability were found in rating the lesion size (0.75 0.81, P=.001), anteroposterior supraglottic activity (0.64, P=.001), and glottal closure (0.65, P=.001). Inter-rater reliability in evaluating the mediolateral supraglottic activity and the amplitude of vocal fold vibration were low to moderate (0.50 and 0.46, respectively, P=.001), whereas the intrarater reliability was more variable (0.2-0.70). CONCLUSIONS: The findings indicated that the evaluation of static structures like lesion size rating, the anteroposterior supraglottic compression, and the glottal closure is a relatively reliable method. The evaluation of dynamic structures, such as the vocal fold vibratory amplitude measure was, however, found to be of low reliability. LEVEL OF EVIDENCE: NA. PMID- 24222187 TI - Movement disorders associated with CLIPPERS. PMID- 24222188 TI - Transmission modes and the evolution of virulence : With special reference to cholera, influenza, and AIDS. AB - Application of evolutionary principles to epidemiological problems indicates that cultural characteristics influence the evolution of parasite virulence by influencing the success of disease transmission from immobilized, infected hosts. This hypothesis is supported by positive correlations between virulence and transmission by biological vectors, water, and institutional attendants. The general evolutionary argument is then applied to the causes and consequences of increased virulence for three diseases: cholera, influenza and AIDS. PMID- 24222189 TI - Culture and the evolution of obesity. AB - Human predispositions to fatness and obesity are best understood in the context of cultural and biological evolution. Both genes and cultural traits that were adaptive in the context of past food scarcities play a role today in the etiology of maladaptive adult obesity. The etiology of obesity must account for the social distribution of the condition with regard to gender, ethnicity, social class, and economic modernization. This distribution, which has changed throughout history, undoubtedly involves cultural factors. A model of culture is presented that has advantages over an undifferentiated concept of the "environment" for hypothesis generation. Cultural predispositions to obesity are found in the productive economy, the mode of reproduction, social structure, and cultural beliefs about food and ideal body size. Cross-cultural comparison can contribute to an understanding of the prevalence of obesity in some modern affluent societies. PMID- 24222190 TI - Physical violence, child abuse, and child homicide : A continuum of violence, or distinct behaviors? AB - The study of child abuse and child homicide has been based on the often implicit assumption that there is a continuum of violence ranging from mild physical punishment to severe abuse and homicide. Empirical data supporting this assumption are sparse. Existing data can be shown, however, to support an assumption that there are distinct forms of violence, not a continuum. This paper reviews these data and discusses their implications for the study of violence, abuse, and homicide in terms of substantive and methodological explanations. In addition, the implications of the assumption that violence consists of distinct behaviors as opposed to a continuum are discussed in light of sociobiological and evolutionary explanations of child abuse and child homicide. PMID- 24222191 TI - Conserving resources for children. AB - Parents can benefit their offspring by conserving resources that the offspring stand to inherit. Thus, inheritance of resources should promote the evolution of propensities to conserve. But inheritance also has another, less obvious effect: it can reduce the fertility of the conserver's grandchildren, thus reducing the expected number of great-grandchildren. Consequently, inheritance of resources promotes the evolution of conservation less than might be supposed. PMID- 24222192 TI - Hair analysis in the detection of long-term use of non-steroidal anti inflammatory drugs and its relation to gastrointestinal hemorrhage: an examination of 268 hair and blood samples from autopsy cases. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics and antipyretics in Western countries. Gastrointestinal (GI) disorders are common side effects of NSAIDs and other drugs. This study investigated the correlation between chronic use of these substances and GI lesions by analyzing postmortem blood and hair samples from autopsy cases. This study included 268 hair and blood samples from autopsy cases. Deceased individuals with GI lesions were selected for the case group (n = 132) and those without any GI lesions were placed in the control group (n = 136). Collection of the samples took place from 2008 until 2010 at the Institute of Legal Medicine and Forensic Sciences, Charite Universitatsmedizin Berlin, Germany. HPLC-DAD was used to analyze the blood samples while hair samples were analyzed using LC-quadrupole-time-of-flight-MS. The proximal 0-6 cm hair segment was analyzed. The full length of shorter hair samples was analyzed when longer segments were unavailable. Method validation was performed according to the guidelines of the German Society of Toxicological and Forensic Chemistry (GTFCh). Twenty-three per cent of the case group blood samples included one or more NSAIDs while 19 % of the control group blood samples included one or more NSAIDs. In contrast, the hair analysis results demonstrated that samples from the control and case group differed significantly; 67 % of the case group tested positive for one or more NSAIDs while 38 % of the control group tested positive for one or more NSAIDs. Hair analysis results provided a strong indication of a relationship between frequent NSAID consumption and GI lesions. PMID- 24222193 TI - Factors associated with social interactions between deaf children and their hearing peers: a systematic literature review. AB - Research indicates that deaf children can have marked social difficulties compared with their hearing peers. Factors that influence these social interactions need to be reviewed to inform interventions. A systematic search of 5 key databases and 3 specialized journals identified 14 papers that met the inclusion criteria. Methodological quality of the articles was assessed using an adapted checklist. There was a general lack of consensus across studies. The main factors investigated were the deaf child's communication competency, age, and level of mainstreaming, which overall were positively associated with peer interactions. Some studies also found that females were more likely to have positive social interactions. The majority of studies were cross-sectional. Some studies lacked appropriate control groups and did not recruit an appropriate range of informants. A wide range of factors were associated with social interactions between deaf and hearing children. The role of communication gained the highest consensus across studies. Other factors were involved in more complex interactions. PMID- 24222194 TI - Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. AB - BACKGROUND: This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. METHODS: A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a >= 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). RESULTS: In the T-DM1 arm, 450 of 495 patients had a baseline and >= 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. CONCLUSIONS: Together with the EMILIA primary data, these results support the concept that T DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life. PMID- 24222195 TI - Dynamic kinetic asymmetric transformations of beta-stereogenic alpha-ketoesters by direct aldolization. AB - Dynamic kinetic asymmetric transformations (DyKAT) of racemic beta-bromo-alpha keto esters by direct aldolization of nitromethane and acetone provide access to fully substituted alpha-glycolic acid derivatives bearing a beta-stereocenter. The aldol adducts are obtained in excellent yield with high relative and absolute stereocontrol under mild reaction conditions. Mechanistic studies determined that the reactions proceed through a facile catalyst-mediated racemization of the beta bromo-alpha-keto esters under a DyKAT Type I manifold. PMID- 24222196 TI - Adaptive mutation in nuclear export protein allows stable transgene expression in a chimaeric influenza A virus vector. AB - The development of influenza virus vectors with long insertions of foreign sequences remains difficult due to the small size and instable nature of the virus. Here, we used the influenza virus inherent property of self-optimization to generate a vector stably expressing long transgenes from the NS1 protein ORF. This was achieved by continuous selection of bright fluorescent plaques of a GFP expressing vector during multiple passages in mouse B16f1 cells. The newly generated vector acquired stability in IFN-competent cell lines and in vivo in murine lungs. Although improved vector fitness was associated with the appearance of four coding mutations in the polymerase (PB2), haemagglutinin and non structural (NS) segments, the stability of the transgene expression was dependent primarily on the single mutation Q20R in the nuclear export protein (NEP). Importantly, a longer insert, such as a cassette of 1299 nt encoding two Mycobacterium tuberculosis Esat6 and Ag85A proteins, could substitute for the GFP transgene. Thus, the inherent property of the influenza virus to adapt can also be used to adjust a vector backbone to give stable expression of long transgenes. PMID- 24222197 TI - Segmentation of scanning electron microscopy images from natural rubber samples with gold nanoparticles using starlet wavelets. AB - Electronic microscopy has been used for morphology evaluation of different materials structures. However, microscopy results may be affected by several factors. Image processing methods can be used to correct and improve the quality of these results. In this article, we propose an algorithm based on starlets to perform the segmentation of scanning electron microscopy images. An application is presented in order to locate gold nanoparticles in natural rubber membranes. In this application, our method showed accuracy greater than 85% for all test images. Results given by this method will be used in future studies, to computationally estimate the density distribution of gold nanoparticles in natural rubber samples and to predict reduction kinetics of gold nanoparticles at different time periods. PMID- 24222198 TI - Osteopenia: debates and dilemmas. AB - Whether or not to use pharmacologic agents for primary prevention of fracture among elderly men and women with osteopenia is debated by clinicians. In this review we provide an update to enable better understanding and characterization of this population, including the prevalence of osteopenia, transitioning from osteopenia to osteoporosis, and clinically applicable tools for fracture risk assessment. We also emphasize the very limited evidence of the benefits and risks of anti-osteoporotic agents for this population for primary fracture prevention, and the need for future studies to guide clinical practice. PMID- 24222206 TI - The limbic system and culture : An allometric analysis of the neocortex and limbic nuclei. AB - The human ability to live according to learned, shared rules of behavior requires cortical functions. Is the limbic system also necessary for culture or are its functions opposed to it, requiring cortical inhibition? The sizes of monkey and ape neocortical and major limbic structures scale with brain weight, but the neocortex expands more (has a steeper exponent) than limbic structures. As the human brain evolved it did not deviate from the scaling relationships found in nonhuman anthropoids. This evidence for conservation in scaling supports the idea that limbic functions are necessary for human symbolism and culture. PMID- 24222207 TI - Culture, biology, and human behavior : A mechanistic approach. AB - Social scientists have not integrated relevant knowledge from the biological sciences into their explanations of human behavior. This failure is due to a longstanding antireductionistic bias against the natural sciences, which follows on a commitment to the view that social facts must be explained by social laws. This belief has led many social scientists into the error of reifying abstract analytical constructs into entities that possess powers of agency. It has also led to a false nature-culture dichotomy that effectively undermines the place of biology in social scientific explanation. Following the principles of methodological individualism, we show how behavioral explanations supported by data and theory from the neurosciences can be used to correct the errors of reificationist thinking in the social sciences. We outline a mechanistic approach to the explanation of human behavior with the hope that the biological sciences will begin to find greater acceptance among social scientists. PMID- 24222205 TI - Human neuropsychology and the concept of culture. AB - American anthropology is distinguished by a four-fields approach in which biological, cultural, archaeological, and linguistic dimensions of behavior are examined in evolutionary and cross-cultural perspective. Nevertheless, assumptions of mind-body dualism pervade scholarly thinking in anthropology and have prevented the development of a truly integrated science of human experience. This dualism is most exemplified by the lack of consideration of the role of the brain in both "physical" and "mental" processes, including phenomena labeled as cultural. In this paper, I review neural mechanisms of learning, communication, and emotion, and discuss the implications of these findings for culture theory. PMID- 24222208 TI - PSAR-align: improving multiple sequence alignment using probabilistic sampling. AB - SUMMARY: We developed PSAR-Align, a multiple sequence realignment tool that can refine a given multiple sequence alignment based on suboptimal alignments generated by probabilistic sampling. Our evaluation demonstrated that PSAR-Align is able to improve the results from various multiple sequence alignment tools. AVAILABILITY AND IMPLEMENTATION: The PSAR-Align source code (implemented mainly in C++) is freely available for download at http://bioen compbio.bioen.illinois.edu/PSAR-Align. PMID- 24222209 TI - tRanslatome: an R/Bioconductor package to portray translational control. AB - High-throughput technologies have led to an explosion of genomic data available for automated analysis. The consequent possibility to simultaneously sample multiple layers of variation along the gene expression flow requires computational methods integrating raw information from different '-omics'. It has been recently demonstrated that translational control is a widespread phenomenon, with profound and still underestimated regulation capabilities. Although detecting changes in the levels of total messenger RNAs (mRNAs; the transcriptome), of polysomally loaded mRNAs (the translatome) and of proteins (the proteome) is experimentally feasible in a high-throughput way, the integration of these levels is still far from being robustly approached. Here we introduce tRanslatome, a new R/Bioconductor package, which is a complete platform for the simultaneous pairwise analysis of transcriptome, translatome and proteome data. The package includes most of the available statistical methods developed for the analysis of high-throughput data, allowing the parallel comparison of differentially expressed genes and the corresponding differentially enriched biological themes. Notably, it also enables the prediction of translational regulatory elements on mRNA sequences. The utility of this tool is demonstrated with two case studies. AVAILABILITY AND IMPLEMENTATION: tRanslatome is available in Bioconductor. PMID- 24222210 TI - DoMosaics: software for domain arrangement visualization and domain-centric analysis of proteins. AB - DoMosaics is an application that unifies protein domain annotation, domain arrangement analysis and visualization in a single tool. It simplifies the analysis of protein families by consolidating disjunct procedures based on often inconvenient command-line applications and complex analysis tools. It provides a simple user interface with access to domain annotation services such as InterProScan or a local HMMER installation, and can be used to compare, analyze and visualize the evolution of domain architectures. AVAILABILITY AND IMPLEMENTATION: DoMosaics is licensed under theApache License, Version 2.0, and binaries can be freely obtained from www.domosaics.net. PMID- 24222211 TI - Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors. AB - BACKGROUND: Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known. METHODS: The authors performed a single-arm phase 2 study of the aromatase inhibitor letrozole at a dose of 2.5 mg daily in patients with unresectable ULMS with ER and/or PR expression confirmed by immunohistochemistry. Tumor assessments were performed at baseline, 6 weeks, 12 weeks, and every 8 weeks thereafter. Toxicity was monitored throughout treatment. The primary endpoint was the progression-free survival at 12 weeks. RESULTS: A total of 27 patients was accrued, with a median of 2 prior treatment regimens (range, 0-9 treatment regimens). The median duration of protocol treatment was 2.2 months (range, 0.4 months-9.9 months). The 12-week progression free survival rate was 50% (90% confidence interval, 30%-67%). The best response was stable disease in 14 patients (54%; 90% CI, 36%-71%). Three patients, all of whom had tumors expressing ER and PR in > 90% of tumor cells, continued to receive letrozole for > 24 weeks. The most common reason for treatment discontinuation was disease progression (85%). Letrozole was found to be well tolerated. CONCLUSIONS: Letrozole met protocol-defined criteria as an agent with activity in patients with advanced ULMS. Patients with the longest progression free survival rate were those whose tumors strongly and diffusely expressed ER and PR. PMID- 24222212 TI - Surgical management of juvenile nasopharyngeal angiofibroma: analysis of 162 cases from 1995 to 2012. AB - OBJECTIVES/HYPOTHESIS: The purpose of this study was to report on a series of 162 patients presenting with juvenile nasopharyngeal angiofibroma in a single academic hospital during the past 17 years, in an effort to compare outcomes between open and transnasal endoscopic approach, and to define an ideal treatment strategy. STUDY DESIGN: Patients who received either open or endoscopic surgery with a minimum follow-up of 6 months were selected. Local control and complications were compared between groups. METHODS: Retrospectively, clinical data, surgical reports, pre- and postoperative images, and follow-up information were reviewed and analyzed. RESULTS: All patients were male subjects from 8 to 41 years old. Ninety-six patients were treated by transpalatal or transmaxillary approach, and the remaining 66 patients were treated using transnasal endoscopic approach with/without labiogingival incision. When compared to the open surgery group, the endoscopic surgery group showed a lower median intraoperative blood loss (800 vs. 1100 mL, P = .017) and a lower number of postoperative complications (one vs. 10). In addition, recurrence statistically correlated with Radkowski's classification and patient age. CONCLUSIONS: Transnasal endoscopic approach can be successfully used for Radkowski's stages I-IIb tumors and selective IIc-IIIb lesions, allowing for less blood loss, fewer postoperative complications, and a lower percentage of recurrence in comparison to open surgery. The management of recurrent tumor is complex, should be individually tailored, and should take into account tumor location, patient age, complications of treatment, and the possibility of spontaneous involution, to better define treatment strategy. PMID- 24222215 TI - Reduced genetic diversity in endemic Brazilian Lymania spp (Bromeliaceae) populations and implications for conservation. AB - We analyzed the genetic diversity of populations of two sympatric species of Lymania (Bromeliaceae), both endemic to the Atlantic rainforest of southern Bahia (Brazil). Lymania azurea has a restricted occurrence, while Lymania smithii has a wider distribution. Our aim was to provide genetic data to contribute to the design of more efficient conservation strategies for these bromeliads, possibly justifying inclusion in the official Brazilian list of Endangered Species. Up to now, L. azurea has been classified by the Brazilian Ministry of the Environment as "data deficient". We sampled four populations of L. azurea throughout its distribution area in southern Bahia and two populations of L. smithii in the same region. Genotyping was performed with 48 random amplified polymorphic DNA markers. Based on the Jaccard genetic similarity index, L. smithii has greater diversity than L. azurea. An analysis of molecular variation showed greater genetic variance within than between populations for both species. L. azurea was found to have 20% inbreeding, probably due to population fragmentation, with L. smithii showing only 10%. When we analyzed pairs of populations of L. azurea within a conservation unit, we found low population structure (FST = 0.098), apparently due to a large degree of gene flow between them. In disturbed areas, we found a higher FST (0.372). We found low genetic variability for L. azurea, probably as a consequence of habitat fragmentation, supporting the need for its inclusion in the Brazilian list of endangered flora. PMID- 24222214 TI - Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice. AB - The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9-12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9- and 12 month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age- and sex-dependent manner. PMID- 24222213 TI - Genome-wide annotation, expression profiling, and protein interaction studies of the core cell-cycle genes in Phalaenopsis aphrodite. AB - Orchidaceae is one of the most abundant and diverse families in the plant kingdom and its unique developmental patterns have drawn the attention of many evolutionary biologists. Particular areas of interest have included the co evolution of pollinators and distinct floral structures, and symbiotic relationships with mycorrhizal flora. However, comprehensive studies to decipher the molecular basis of growth and development in orchids remain scarce. Cell proliferation governed by cell-cycle regulation is fundamental to growth and development of the plant body. We took advantage of recently released transcriptome information to systematically isolate and annotate the core cell cycle regulators in the moth orchid Phalaenopsis aphrodite. Our data verified that Phalaenopsis cyclin-dependent kinase A (CDKA) is an evolutionarily conserved CDK. Expression profiling studies suggested that core cell-cycle genes functioning during the G1/S, S, and G2/M stages were preferentially enriched in the meristematic tissues that have high proliferation activity. In addition, subcellular localization and pairwise interaction analyses of various combinations of CDKs and cyclins, and of E2 promoter-binding factors and dimerization partners confirmed interactions of the functional units. Furthermore, our data showed that expression of the core cell-cycle genes was coordinately regulated during pollination-induced reproductive development. The data obtained establish a fundamental framework for study of the cell-cycle machinery in Phalaenopsis orchids. PMID- 24222216 TI - Endothelial cells on the proliferation and expression of intercellular adhesion molecule 1 and interleukin 8 of vascular smooth muscle cells. AB - The aim of this study was to investigate the influence of activated endothelial cells on the proliferation and secretion of vascular smooth muscle cells (VSMCs). Cultured lung microvascular endothelial cells were treated with or without tumor necrosis factor alpha (TNF-alpha; 10 ng/mL) for 6 h, and the supernatant was collected and filtered. The supernatant with TNF-alpha was called fluid A, and that without TNF-alpha was called fluid B. VSMCs were cultured and divided into 3 groups with different media as follows: activated medium [fluid A and Dulbecco's modified Eagle medium (DMEM); activated group], inactivated medium (fluid B and DMEM; inactivated group), and DMEM only (control group) for 24 h. Intercellular adhesion molecule 1 (ICAM-1), interleukin (IL)-8, and IL-6 levels in the supernatant of VSMCs were measured with enzyme-linked immunosorbent assay 0 and 24 h after grouping. The proliferation of VSMCs was detected with 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ICAM-1 and IL 8 increased above baseline values in the 3 groups; the maximum increase occurred in activated medium. The optical densities in MTT assay of the activated, inactivated, and control groups was 1.35 +/- 0.11, 1.01 +/- 0.09, and 0.29 +/- 0.01, respectively, which correlated positively with the initial IL-6 level in the supernatant of the VSMCs (r = 0.63, P < 0.05). TNF-alpha-activated endothelial cells promote VSMC proliferation and secretion of ICAM-1 and IL-8 by elevating IL-6 release. PMID- 24222217 TI - Antibody-based detection of alkaline phosphatase in lepidopteran insects (Lepidoptera: Noctuidae). AB - Alkaline phosphatase (ALP) of Helicoverpa armigera Hub. (Lepidoptera; Noctuidae) (GenBank accession No. EU729322) was cloned and expressed. The target gene H.a ALP, having an open reading frame of 1608 bp, was reverse-transcribed from cDNA by the polymerase chain reaction. The open reading frame of the target gene was cloned into the pET-32a expression vector to obtain recombinant protein in Escherichia coli DE-3 cells for the subsequent production of polyclonal antibody. New Zealand white rabbits were used for production of anti-pET-32a-H.a-ALP. The production of antibody was also optimized by employing ELISA for titer determination. The produced antiserum was processed and used as an antibody. Western blot results showed that the polyclonal antibody produced was capable of effectively binding target protein not only from H. armigera but also from other lepidopterans such as Mythimna separata and Plutella xylostella. This antibody was also used to detect levels of ALP within different instars of H. armigera. Thus, it is concluded that this antibody-based assay is very useful for the effective detection of gene-specific expression. Furthermore, it may also be used to detect the expression levels and tissue localization of ALP, as well as in other physiological studies involving this enzyme. PMID- 24222218 TI - Relationship between dilated cardiomyopathy and the E23K and I337V polymorphisms in the Kir6.2 subunit of the KATP channel. AB - ATP-sensitive potassium channels play an important role in myocardial electrical activity. Genetic disruption of these channels predisposes the myocardium to cardiac diseases. Herein we investigated whether two polymorphisms, E23K and I337V, located in the Kir6.2 subunit of ATP-sensitive potassium channels are associated with dilated cardiomyopathy (DCM) in a Chinese population. Blood was collected from DCM patients and controls. DNA was extracted for polymerase chain reaction, which was followed by DNA sequencing. The 2 polymorphisms were present in both DCM patients and normal controls. The frequencies of both the E23K and the I337V polymorphisms were not significantly different between DCM patients and normal controls. However, in DCM patients carrying the E23K polymorphism, the left ventricular end diastolic dimension (LVEDD) and the left atrial dimension (LAD) were significantly greater than those in DCM patients without the E23K polymorphism. Moreover, the occurrence of ventricular arrhythmias in DCM patients was also slightly increased in the presence of the E23K polymorphism (P < 0.05). We failed to identify an association between the I337V polymorphism and LVEDD, LAD, or ventricular arrhythmias in patients with DCM. The Kir6.2 E23K polymorphism in DCM patients of Han ethnicity may increase the risk of negative outcomes such as congestive heart failure and sudden cardiac death by affecting LVEDD and LAD. PMID- 24222219 TI - Molecular and biochemical characterization of the effects of insecticidal toxin from Meloidae beetles on Helicoverpa armigera (Hub.) (Lepidoptera: Noctuidae). AB - The molecular and biochemical effects of an insecticidal toxin extracted from Meloidae beetles were investigated on Helicoverpa armigera. The toxin was identified as cantharidin, a well-known natural compound produced by beetles of family Meloidae and Oedemeridae. Furthermore, the effect of the toxin on the metabolic enzymes alkaline phosphatase (ALP) and glutathione S-transferase (GST), responsible for the metabolism of insecticides, was also investigated. Results of a diet incorporation bioassay performed under laboratory conditions showed that the LC50 value of cantharidin was 0.068 mg/g. The body weight of the insect was also significantly reduced by cantharidin treatment. The LC10 concentration of cantharidin, 0.01 mg/g, was also tested to determine its effect on ALP and GST. Our results showed that cantharidin significantly inhibited ALP activity after 48 h, whereas GST activity was significantly inhibited after 24 h. The decline of ALP and GST transcript levels was also validated by semiquantitative RT-PCR analysis. It may be concluded from the results that ALPs and GSTs may be targets of the cantharidin intoxication mechanism. Moreover, the inability of ALP and GST to metabolize cantharidin shows that the mechanism of detoxification for cantharidin is different from that for conventional insecticides. On the basis of our investigations, the chemical structure of insecticides may be modified using a model structure of cantharidin, to avoid metabolism by metabolic enzymes. PMID- 24222220 TI - Molecular cloning and expression of the porcine S14R gene in Escherichia coli. AB - We amplified S14R protein gene cDNA of porcine, cloned it into a prokaryotic expression plasmid, and expressed it in Escherichia coli. A pair of primers was designed based on the cDNA sequence of the porcine S14R gene in GenBank. The target gene fragment from porcine liver tissue was amplified by RT-PCR. Confirmed by auto-sequencing, the target gene fragment was subcloned into an expression vector of pET28a. The pET28a-S14R construct was subsequently transformed into E. coli BL21 (DE3). This construct was verified by restriction endonuclease digestion and sequencing. Using isopropyl beta-D-1-thiogalactopyranoside induction, a new recombinant protein with the expected relative molecular mass of 24 kDa appeared. The result was identified by SDS-PAGE electrophoresis. Porcine S14R includes 549bp (GenBank No. JN793537), with an open reading frame of 549 bp coding 182 amino acids. PMID- 24222221 TI - Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response. AB - Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify 2 and 3 of CYP2C9, 2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the 1 1 and 1 2 groups, with effective acenocoumarol doses of 2.56 +/- 1.34 mg/day vs 1.35 +/- 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19 2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients. PMID- 24222222 TI - Bioprospection of bacteria and yeasts from Atlantic Rainforest soil capable of growing in crude-glycerol residues. AB - The increasing world production of biodiesel has resulted in an accumulation of crude glycerol as the major byproduct. This could be used as carbon source for industrial microbiology, with economic and environmental advantages for the biodiesel industry. We explored an Atlantic Rainforest soil sample to search for crude glycerol-degrading microorganisms. Microcosms of this soil were established containing minimal medium + 8% crude glycerol (w/w); the biological activity was measured by respirometry. High CO2 levels were found in some of the crude glycerol microcosms, suggesting the activity of microorganisms capable of degrading this residue. In an attempt to isolate and cultivate these microorganisms in vitro, aliquots of the soil suspension were plated on minimal medium containing 10% crude glycerol (v/v). Out of 19 morphologically distinct isolates, 12 bacteria and 6 yeasts were identified by PCR from universal primers 16S and 26S rDNA, respectively. Optical density readings revealed growth differences among cultures. Two yeasts and three bacteria with distinct growth profiles stood out and appeared to have potential for liquid fermentation of crude glycerol. The yeasts adapted rapidly, but produced relatively little biomass. Opposite tendencies were found in the bacteria. Amplicon sequencing placed the bacterial isolates as close to Staphylococcus arlettae, Pseudomonas citronellolis, and Bacillus megaterium, and the yeasts to Trichosporon moniliiforme and Meyerozyma guilliermondii. We concluded that these species have potential for use in crude glycerol bioreactors and for bioremediation processes. PMID- 24222223 TI - Complete mitochondrial genomes of the Bright Sunbeam Curetis bulis and the Small Copper Lycaena phlaeas (Lepidoptera: Lycaenidae) and their phylogenetic implications. AB - In this study, the complete mitochondrial genomes of Curetis bulis and Lycaena phlaeas were determined and analyzed. The circular genomes are 15,162 bp long for C. bulis and 15,280 bp long for L. phlaeas, with a total A+T content of 82.6 and 83.1%, respectively. Both mitogenomes contain 37 genes, and their gene orders are similar to those of other lepidopterans. All protein-coding genes (PCGs) are initiated by ATN codons, except for cox1, which is started with the CGA codon; all PCGs terminate in the typical stop codon TAA, except for cox1, cox2, and nad4, which end with a single T. The codons TTA (Leu), ATT (Ile), TTT (Phe), ATA (Met), and AAT (Asn) appear the most frequently. Both of the mitogenome A+T-rich regions harbor the motif ATAGA, followed by a 19-bp poly(T) stretch, with C. bulis containing a microsatellite-like (AT)5 element next to the ATTTA motif, and L. phlaeas containing a microsatellite-like (TA)6 (AT) element next to the ATTTA motif. The phylogenetic trees of the 17 representative butterfly species, including the two species of this study, were reconstructed with the maximum likelihood and Bayesian inference methods, based on the 13 PCG nucleotide sequence data. The results of the phylogenetic analyses strongly supported the relationships of ((((Lycaenidae + Pieridae) + Nymphalidae) + Hesperiidae) + Papilionidae), which was markedly different from the traditional morphological view of the Lycaenidae and Nymphalidae considered to be sisters of each other. PMID- 24222224 TI - Mutational analysis of AXIN2, MSX1, and PAX9 in two Mexican oligodontia families. AB - The genes for axin inhibition protein 2 (AXIN2), msh homeobox 1 (MSX1), and paired box gene 9 (PAX9) are involved in tooth root formation and tooth development. Mutations of the AXIN2, MSX1, and PAX9 genes are associated with non syndromic oligodontia. In this study, we investigated phenotype and AXIN2, MSX1, and PAX9 gene variations in two Mexican families with non-syndromic oligodontia. Individuals from two families underwent clinical examinations, including an intra oral examination and panoramic radiograph. Retrospective data were reviewed, and peripheral blood samples were collected. The exons and exon-intronic boundaries of the AXIN2, MSX1, and PAX9 genes were sequenced and analyzed. Protein and messenger RNA structures were predicted using bioinformative software programs. Clinical and oral examinations revealed isolated non-syndromic oligodontia in the two Mexican families. The average number of missing teeth was 12. The sequence analysis of exons and exon-intronic regions of AXIN2, MSX1, and PAX9 revealed 11 single-nucleotide polymorphisms (SNPs), including seven in AXIN2, two in MSX1, and three in PAX9. One novel SNP of MSX1, c.476T>G (Leu159Arg), was found in all of the studied patients in the families. MSX1 Leu159Arg and PAX9 Ala240Pro change protein and messenger RNA structures. Our findings suggested that a combined reduction of MSX1 and PAX9 gene dosages increased the risk for oligodontia in the Mexican families, as in vivo investigation has indicated that interaction between Msx1 and Pax9 is required for tooth development. PMID- 24222225 TI - Comparison of period-3 correlation amplitudes in genomic DNA sequences. AB - Period-3 oscillations in genome composition can be detected through correlation functions. Since these oscillations are closely related to the genetic code structure, we developed methods for quantitative comparison of genomic and exonic oscillation amplitudes and decay. In contrast to genomic correlations, exonic period-3 oscillation amplitudes are persistent. A model postulating an uncorrelated distribution of exons in the genome has been applied to the analysis of Escherichia coli K12, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens genomic decay, allowing for a quantitative discussion of genome organization. PMID- 24222226 TI - Bayesian network structure learning based on the chaotic particle swarm optimization algorithm. AB - The Bayesian network (BN) is a knowledge representation form, which has been proven to be valuable in the gene regulatory network reconstruction because of its capability of capturing causal relationships between genes. Learning BN structures from a database is a nondeterministic polynomial time (NP)-hard problem that remains one of the most exciting challenges in machine learning. Several heuristic searching techniques have been used to find better network structures. Among these algorithms, the classical K2 algorithm is the most successful. Nonetheless, the performance of the K2 algorithm is greatly affected by a prior ordering of input nodes. The proposed method in this paper is based on the chaotic particle swarm optimization (CPSO) and the K2 algorithm. Because the PSO algorithm completely entraps the local minimum in later evolutions, we combined the PSO algorithm with the chaos theory, which has the properties of ergodicity, randomness, and regularity. Experimental results show that the proposed method can improve the convergence rate of particles and identify networks more efficiently and accurately. PMID- 24222227 TI - Analysis of differentially expressed genes in various stages of Duchenne muscular dystrophy by using a network view. AB - Duchenne muscular dystrophy (DMD), which is caused by mutations in the X-linked dystrophin gene, is a severe and progressive neuromuscular disease with no available cure. By integrating 2 microarray datasets from the Gene Expression Omnibus, we identified differentially expressed genes in 2 stages of DMD and systematically explored their potential disease-related mechanisms using a network view. Twenty differentially expressed genes were detected in various stages of DMD. According to the network with dystrophin as its center, none of the 20 proteins interacts with dystrophin directly. IQ motif-containing GTPase activating protein 1 was found in the 2nd-level neighbors with a degree of 21. Microtubule-associated protein tau, membrane metallo-endopeptidase, interleukin 13 receptor alpha 1, and multiple epidermal growth factor-like domains 6 were found in the 3rd-level neighbors. These identifications require further investigation, as this report is the first of possible associations between DMD and these proteins. Analysis of differentially expressed genes through this network view may provide important information for further exploration of underlying mechanisms of DMD. PMID- 24222228 TI - A high-throughput, high-quality plant genomic DNA extraction protocol. AB - The isolation of high-quality genomic DNA (gDNA) is a crucial technique in plant molecular biology. The quality of gDNA determines the reliability of real-time polymerase chain reaction (PCR) analysis. In this paper, we reported a high quality gDNA extraction protocol optimized for real-time PCR in a variety of plant species. Performed in a 96-well block, our protocol provides high throughput. Without the need for phenol-chloroform and liquid nitrogen or dry ice, our protocol is safer and more cost-efficient than traditional DNA extraction methods. The method takes 10 mg leaf tissue to yield 5-10 ug high quality gDNA. Spectral measurement and electrophoresis were used to demonstrate gDNA purity. The extracted DNA was qualified in a restriction enzyme digestion assay and conventional PCR. The real-time PCR amplification was sufficiently sensitive to detect gDNA at very low concentrations (3 pg/uL). The standard curve of gDNA dilutions from our phenol-chloroform-free protocol showed better linearity (R(2) = 0.9967) than the phenol-chloroform protocol (R(2) = 0.9876). The results indicate that the gDNA was of high quality and fit for real-time PCR. This safe, high-throughput plant gDNA extraction protocol could be used to isolate high-quality gDNA for real-time PCR and other downstream molecular applications. PMID- 24222229 TI - Meta-analysis demonstrates lack of an association of microsomal epoxide hydrolase 1 polymorphisms with esophageal cancer risk. AB - Epoxide hydrolases metabolize exogenous chemicals, including carcinogens such as polycyclic aromatic hydrocarbons. The relationship between microsomal epoxide hydrolase 1 (EPHX1) polymorphisms and esophageal cancer risk has been investigated in various ethnic populations, but the results have been contradictory. We investigated the association of EPHX1 Tyr113His and His139Arg polymorphisms with esophageal cancer via a comprehensive meta-analysis. Publications before August 20, 2012 were included. Eight studies concerning Tyr113His polymorphism associated with 1158 esophageal cancer cases and 1868 controls were identified; 7 studies concerning association of His139Arg with 901 esophageal cancer cases and 1615 controls were also included. A random-effect model was applied, irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. No significant association was found in either the allele or genotype models for Tyr113His or His139Arg polymorphism with risk for esophageal cancer. Lack of association was also identified in stratified analyses by ethnicity. No publication bias was observed. We conclude that current evidence does not demonstrate association of EPHX1 Tyr113His or His139Arg polymorphisms with risk for development of esophageal cancer. PMID- 24222230 TI - Culture-independent analysis of endophytic bacterial communities associated with Brazilian sugarcane. AB - Sugarcane is an economically important culture in Brazil. Endophytic bacteria live inside plants, and can provide many benefits to the plant host. We analyzed the bacterial diversity of sugarcane cultivar RB-72454 by cultivation-independent techniques. Total DNA from sugarcane stems from a commercial plantation located in Parana State was extracted. Partial 16S rRNA genes were amplified and sequenced for library construction. Of 152 sequences obtained, 52% were similar to 16S rRNA from Pseudomonas sp, and 35.5% to Enterobacter sp. The genera Pantoea, Serratia, Citrobacter, and Klebsiella were also represented. The endophytic communities in these sugarcane samples were dominated by the families Enterobacteriaceae and Pseudomonadaceae (class Gammaproteobacteria). PMID- 24222231 TI - Genetic polymorphisms of LPL and HL and their association with the performance of Chinese sturgeons fed a formulated diet. AB - It is very important to investigate the reasons for the large individual differences in individual performance of food acceptance when using formulated diets for the successful culture of larvae and juveniles of the Chinese sturgeon Acipenser sinensis. Genetic differences of the mitochondrial control region were investigated by direct sequencing in two groups of Chinese sturgeon, which were apt to accept or refuse formulated diets. Among 968-bp sequences, 111 variable sites were identified. One variable site showed close association with the individual performance of specimens fed with formulated diets. The commercial diet for Chinese sturgeons usually contains high levels of lipids. Lipoprotein lipase (LPL) and hepatic lipase (HL) are two members of the lipase gene family, which are essential for the utilization of dietary lipid. Single nucleotide polymorphisms (SNPs) in intron 7 were detected in the two experimental groups of Chinese sturgeons. We were able to demonstrate that one SNP in the LPL gene and one SNP in the HL gene showed close association with the performance of sturgeons on the formulated diet. PMID- 24222232 TI - RUNX2 mutations in cleidocranial dysplasia. AB - The runt-related transcription factor 2 gene (RUNX2), which is also known as CBFA1, is a master regulatory gene in bone formation. Mutations in RUNX2 have been identified in cleidocranial dysplasia (CCD) patients. CCD is a rare autosomal dominant skeletal dysplasia that is characterized by delayed closure of cranial sutures, aplastic or hypoplastic clavicle formation, short stature, and dental anomalies, including malocclusion, supernumerary teeth, and delayed eruption of permanent teeth. In this study, we recruited three de novo CCD families and performed mutational analysis of the RUNX2 gene as a candidate gene approach. The mutational study revealed three disease-causing mutations: a missense mutation (c.674G>A, p.Arg225Gln), a frameshift mutation (c.1119delC, p.Arg374Glyfs*), and a nonsense mutation (c.1171C>T, p.Arg391*). Clinical examination revealed a unique dental phenotype (no typical supernumerary teeth, but duplication of anterior teeth) in one patient. We believe that this finding will broaden the understanding of the mechanism of supernumerary teeth formation and CCD-related phenotypes. PMID- 24222233 TI - Universal primers to amplify the complete mitochondrial 12S rRNA gene in marine fish species. AB - A pair of new universal 12S mitochondrial rRNA gene primers was designed through multiple alignment analysis of the mitochondrial tRNA(Phe) and the 5' region of 16S mitochondrial rRNA genes of different kinds of fishes. The primers were successfully used to amplify an expected product fragment of about 1.2 kb from various marine fish species, and the amplified DNA fragment was recognized to contain the complete 12S mitochondrial rRNA and tRNA(Val) genes, as well as a partial 16S mitochondrial rRNA gene of about 146 bp in length. The primers would facilitate the study of the species discrimination, population and evolution in marine fish species. PMID- 24222234 TI - Genetic diversity of spineless Cereus jamacaru accessions using morphological and molecular markers. AB - This is the first study to examine the genetic diversity of mandacaru cactus (Cereus jamacaru P. DC.). Plants of spineless mandacaru are commonly found in gardens and parks of urban areas in northeastern Brazil. In addition to exploring their ornamental potential, morphological, and genetic characterization may contribute to the development of plant materials that can be used as a source of macromolecules of potential economic interest. The goal of this study was to estimate the genetic variability of spineless mandacaru accessions using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) molecular markers, and to characterize their morphology. Ten samples of newly emitted shoots with differentiated areolas and ribs were collected from each accession from the Cactaceous Germplasm Collection of Embrapa Agroindustria Tropical, in Fortaleza, CE. Shoot shape and aspects of spine primordia (presence, location, grouping, and size of spines) were evaluated. The morphological analysis showed that the spineless mandacaru presented spine primordia. Twenty six RAPD and 15 ISSR primers were polymorphic. A total of 262 markers were obtained, 129 of which were polymorphic. The average polymorphism of ISSR markers was higher than that of RAPD markers. The dendrograms for both analyses showed differentiation between accessions. Nevertheless, the molecular markers detected higher levels of diversity and a different pattern of diversity than those found using morphological markers. The molecular results revealed significant genetic variability both within and between groups. PMID- 24222235 TI - Effects of metallothionein-3 and metallothionein-1E gene transfection on proliferation, cell cycle, and apoptosis of esophageal cancer cells. AB - Metallothionein (MT)-3 has cell growth inhibitory activity, and is the only currently known MT subtype with unique physiological functions. The expression levels of MT-1E, a subtype of MT-1, were positively correlated with the degree of esophageal cancer malignancy. The present study aimed to investigate the effects of MT-3 and MT-1E gene transfection on the proliferation, cell cycle, and apoptosis of esophageal cancer cells. The cationic liposome method was used to transfect the esophageal cancer strains Eca-109 and TE13. Reverse transcription polymerase chain reaction was used to detect target gene expression, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction was applied to detect cell proliferation, and flow cytometry was used for cell cycle and apoptosis detection. Esophageal cancer cells with MT-3 and MT-1E gene transfection showed high expression of the foreign target gene and mRNA. Cells with MT-3 gene transfection showed markedly inhibited proliferation (P < 0.05), a significantly higher proportion of cells in the G0/G1 phase (P < 0.05), a significantly lower proportion of cells in the S phase (P < 0.05), and a significantly increased apoptosis rate (P < 0.05). Cells with MT-1E gene transfection did not show significant changes in proliferation, cell cycle, or apoptosis rate (P > 0.05). Therefore, the upregulation of MT-3 gene expression can inhibit esophageal cancer cell proliferation and induce apoptosis, which may be achieved by blocking the tumor cell growth cycle, whereas effects of the MT-1E gene on the proliferation of esophageal cancer cells were not evident. PMID- 24222236 TI - Variability analysis of 'Persian' acid lime tree selections using agronomic and molecular markers. AB - 'Persian' acid lime (PAL) is the most important triploid commercial citrus crop planted in the world. Little is known about the genetic variability of the selections used in Brazil. Therefore, 25 genotypes originating from the PAL, and three control species, Citrus sunki, C. limon, and C. aurantiifolia, were assessed using inter-simple sequence repeat (ISSR) and inter-retrotransposon amplified polymorphism (IRAP) molecular markers and agronomic traits of the fruit. The dendrograms were designed using the mean Euclidean distance for the physicochemical attributes of the fruit (weight, length, diameter, peel color, peel thickness, number of seeds, juice yield, titratable acidity, soluble solids, and ratio) and the Jaccard distances using the data from the ISSR and IRAP molecular markers. In the physicochemical analysis, the genotypes were grouped according to species. The trait that contributed most to the diversity among accessions was the number of seeds. The 17 ISSR primers produced 69 polymorphic bands in the molecular analysis, and the seven IRAP primers generated 30 polymorphic bands. The markers detected polymorphisms within and among the PALs; two groups were formed within the PALs. PMID- 24222237 TI - Population variability of Bemisia tabaci (Genn.) in different hosts. AB - The silverleaf whitefly, Bemisia tabaci (Genn.) (Hemiptera: Aleyrodidae), is a cryptic species complex that contains some of the most damaging pests in tropical and subtropical regions. Recent studies have indicated that this complex is composed of at least 24 distinct and morphologically indistinguishable species that mainly differ in their ability to transmit phytoviruses, adapt to hosts, and induce physiological changes in certain hosts. The importance of this species has been increasing worldwide, because it serves as a phytovirus vector, particularly for geminiviruses, in economically important crops. Here, we aimed to examine the population variability of B. tabaci populations inhabiting 6 agricultural crops grown in 5 regions of Brazil and 1 region of the USA; BRrep [Brasilia (DF, Brazil) - cabbage], ILsoj [Urbana (IL/USA) - soybean], BJabo [Bom Jesus da Lapa (BA, Brazil) - pumpkin], CPsoj [Campinas (SP, Brazil) - soybean], UBman [Ubatuba (SP, Brazil) - cassava], and PEmel [Petrolina (PE, Brazil) - melon]. Thirteen polymorphic loci with 50 alleles were observed, with an average of 2.37 (range: 2.00-2.91) alleles per population. The UBman and PEmel B. tabaci populations were the most differentiated, which was probably caused by insect adaptation to the host plant and the use of insecticides. A 33.87% inter-population variation was observed, indicating that microsatellites may be used to measure differentiation among these B. tabaci populations. Based on the comparison of microsatellites in the current study, only the Middle East-Asia Minor 1 population of B. tabaci was found in the six populations. PMID- 24222238 TI - "Extended Fitness" hypothesis: a link between individual and group selection. AB - What are the targets of natural selection remains a controversial issue in Biology. Here I propose the "Extended Fitness" hypothesis, in which extended phenotypes emerge as a link between individual and group selection. The basic premise of the extended fitness hypothesis is that extended phenotypes can be used by members of the same group since they are adapted to use them. Thus, extended phenotypes can also contribute to the fitness of members of the same species. Group selection emerges as a natural consequence of the shared use of extended phenotypes, which allow the evolutionary forces acting on individuals to become effective at the group level. The extended fitness hypothesis is supported by several observations found in nature. The hypothesis presented here provides a theoretical framework for the design of both modeling and experimental approaches to studying the role of extended phenotypes in group selection. PMID- 24222239 TI - Analysis of GATA1 mutations and leukemogenesis in newborns with Down syndrome. AB - It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events. PMID- 24222240 TI - Expression of ADAMTS4 and ADAMTS5 in longissimus dorsi muscle related to meat tenderness in Nanyang cattle. AB - The ADAMTS4 and ADAMTS5 are secreted proteases, which can cleave aggrecan, brevican and versican to regulate rebuilding of the extracellular matrix. We analyzed the ADAMTS4 and ADAMTS5 gene expression patterns in longissimus dorsi muscle at intervals from 135 days fetal age to 30 months old by qRT-PCR in Nanyang cattle. Expression of ADAMTS4 was significantly higher in 135 and 185-day old fetuses than at other stages, while expression of ADAMTS5 decreased during development. The promoter regions of ADAMTS4 and ADAMTS5 were cloned and the transcription factor binding sites were analyzed with bioinformatic methods. Twelve and six potential transcription factor binding sites were found in the promoter regions of ADAMTS4 and ADAMTS5 genes, respectively. Three transcription factors (MZF1, C/EBPb, and NF-kap) were selected to analyze the expression pattern during the development of the longissimus dorsi muscle. MZF1 was significantly co-expressed with ADAMTS4, while C/EBPb expression was significantly negatively associated with that of ADAMTS4. We concluded that the expression of ADAMTS4 is positively regulated by MZF1 and negatively regulated by C/EBPb. We examined the relationships of ADAMTS4 and ADAMTS5 expression with tenderness of longissimus dorsi muscle; ADAMTS4 was significantly and negatively correlated with meat tenderness. We conclude that ADAMTS4 participates in the regulation of muscle development in cattle. PMID- 24222241 TI - Association of NPP1 polymorphism with postoperative progression of ossification of the posterior longitudinal ligament in Chinese patients. AB - Ossification of the posterior longitudinal ligament (OPLL) is a condition of the spine that can cause paralysis by compressing the spinal cord. The aim of this study was to evaluate the possible role of nucleotide pyrophosphatase phosphodiesterase 1 gene (NPP1) polymorphism in the etiology and pathology of the OPLL in Chinese patients. DNA from patients with OPLL (N = 95) and without OPLL (N = 90) were genotyped for 4 NPP1 single-nucleotide polymorphisms (SNPs): A533C, C973T, IVS15-14T->C, and IVS20-11delT. An association study evaluated the relationship between specific SNP genotypes and susceptibility. We also evaluated whether genotypes of these SNPs were associated with disease severity and the probability of disease progression after surgery. The C973T and IVS15-14T SNPs were associated with the existence of the disease. The TT genotypes of C973T and IVS15->14T as well wild-type IVS20 (lack of deletion) were associated with more severe disease. Patients with the T deletion of IVS20 or the AA genotype of A533C had an approximately 3 times greater chance of not having than having disease progression after surgery. We concluded that the 4 SNPs analyzed appeared to have different effects on the etiology and pathology of OPLL. To our knowledge, this study is the first to investigate the relationship between these SNPs and disease progression after surgery. Our findings suggest that the presence of specific genotypes of the IVS20-11delT and A533C SNPs may predict disease outcome after surgical intervention. PMID- 24222242 TI - An efficient algorithm for finding attractors in synchronous Boolean networks with biochemical applications. AB - Self-organized systems, genetic regulatory systems and other living systems can be modeled as synchronous Boolean networks with stable states, which are also called state-cycle attractors (SCAs). This paper summarizes three classes of SCAs and presents a new efficient binary decision diagram based algorithm to find all SCAs of synchronous Boolean networks. After comparison with the tool BooleNet, empirical experiments with biochemical systems demonstrated the feasibility and efficiency of our approach. PMID- 24222243 TI - Karyotype variation in cultivars and spontaneous cocoa mutants (Theobroma cacao L.). AB - Four mutant cocoa accessions with morphological changes and a cultivar sample were karyomorphologically characterized. Slides were prepared by enzymatic digestion of the root meristem and squashed in 45% acetic acid, followed by 2% Giemsa staining. The chromosome number of 2n = 20 was seen in all accessions. The karyotype formula for Cacau Comum and Cacau Rui was 2n = 20m. Submetacentric chromosomes were observed in Cacau Pucala and Cacau Jaca, both with 2n = 18m + 2sm, but the karyotype formula for Cacau Sem Vidro was 2n = 16m + 4sm. Satellites were located on the long arm of the 1st and 2nd chromosome pairs of Cacau Comum, whereas Cacau Pucala had satellites on the 6th chromosome pair. Greater karyotypic variation in Cacau Sem Vidro was found, whose 1st and 2nd chromosome pairs had satellites on the long arm and 6th and 10th pairs had satellites on the short arm. Analysis revealed a lower average chromosome length in Cacau Comum (1.53 +/- 0.026 um) and a higher length in Cacau Sem Vidro (2.26 +/- 0.038 um). ANOVA revealed significant difference (P < 0.01) for the average chromosome length and the length of chromosome pairs within and between accessions. The average chromosome lengths of mutants of Cacau Rui and Cacau Jaca were not statistically different by the Tukey test at 5% probability. The karyotypic diversity observed in this study is not necessarily associated with the changing character of the accessions analyzed, but may reflect the genetic variation observed in Theobroma cacao. PMID- 24222244 TI - Interleukin-1beta +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis. AB - The purpose of this meta-analysis was to determine whether genetic variants of the interleukin-1beta[+3954 C>T (rs1143634)] (IL-1beta +3954 C>T) gene polymorphisms were associated with orthodontic external apical root resorption (EARR). A meta-analysis was carried out using data entered into the PubMed and Embase electronic databases before October 5, 2012. A total of 7 studies were identified for meta-analysis. The strength of the relationship between IL-1beta +3954 C>T polymorphism and the risk of EARR was assessed using odds ratio (OR). The studies provided overall OR estimates for EARR. Overall, the variant genotypes (CC and CT) of the IL-1beta +3954 C>T polymorphism were unassociated with EARR risk compared with the TT homozygote [CC vs TT, OR = 1.28, 95% confidence interval (95%CI) = 0.27-6.08; CT vs TT, OR = 0.74, 95%CI = 0.11-5.02]. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 1.08, 95%CI = 0.24-4.86; recessive model, OR = 1.85, 95%CI = 0.87-3.93). No publication bias was found, and no association was apparent between the IL-1beta +3954 C>T polymorphism and risk of EARR in orthodontic treatment patients. Further multicenter and better-controlled studies are required to confirm these findings. PMID- 24222245 TI - Transcriptome network analysis of potential candidate genes for heart failure. AB - The purpose of this study was to examine the hypothesis that a transcriptome network can be developed through a set of transcription factors regulated by the expression of various genes induced by dilated cardiomyopathy can be identified and modulated to respond to heart failure. We searched for significant pathways related to dilated cardiomyopathy using the GSE4172 microarray data to identify potential genes related to heart failure. We mapped differentially expressed genes to pathways and constructed a regulation network to investigate the regulatory relationships between transcription factors and pathways. Some transcription factors and target genes in the networks have been clearly linked to heart failure in previous studies. We also found new transcription factors and target genes, such as CCAAT/enhancer-binding protein delta and JunB, responsible for inflammatory cardiomyopathy. Transcriptome network analysis was useful in the identification of candidate genes in heart failure. This method is well suited for microarray data and therefore is proposed as a powerful tool in the search for new pathways related to disease. PMID- 24222246 TI - Molecular cloning and expression analysis of two sex-lethal homolog genes during development in the oriental river prawn, Macrobrachium nipponense. AB - In this study, two Sxl gene homologs, designated as Mnsxl1 and Mnsxl2, were cloned and characterized from the freshwater prawn Macrobrachium nipponense by rapid amplification of cDNA ends. The deduced amino acid sequences of Mnsxl1 and Mnsxl2 showed high sequence homology to the insect Sxl and contained conserved domains in two RNA-binding motifs. Real-time quantitative reverse transcription polymerase chain reaction (RT-QPCR) showed that the Mnsxl1 and Mnsxl2 genes were expressed in all investigated tissues, with the highest level of expression in the intestine and liver. RT-QPCR also revealed that Mnsxl1 and Mnsxl2 mRNAs expressions were both significantly increased at 5 and 20 days post-larvae after metamorphosis. Thus, the results of the present study imply that Mnsxl1 and Mnsxl2 play complex and important roles in the sex differentiation of M. nipponense. PMID- 24222247 TI - Expression of cationic amino acid transporters, carcass traits, and performance of growing pigs fed low-protein amino acid-supplemented versus high protein diets. AB - Free amino acids (AA) appear to be absorbed faster than protein-bound AA (PB-AA). We conducted an experiment to assess the effect of feeding pigs with a partially free (F-AA) or totally PB-AA diet on expression of selected genes and performance of pigs. The expression of cationic AA transporters b(0,+) and CAT-1 in intestinal mucosa, liver, and longissimus (LM) and semitendinosus (SM) muscles, as well as that of myosin in LM and SM, was analyzed. Twelve pigs (31.7 +/- 2.7 kg) were used. The F-AA diet was based on wheat, supplemented with 0.59% L-Lys, 0.33% L-Thr, and 0.10% DL-Met. The PB-AA diet was formulated with wheat-soybean meal. Average daily feed intake was 1.53 kg per pig. The expression of b(0,+) and CAT-1 was analyzed in jejunal and ileal mucosa, liver, LM, and SM; myosin expression was also analyzed in both muscles. Pigs fed the PB-AA diet tended to have higher weight gain and feed efficiency (P < 0.10), and had thinner back fat (P = 0.02). The expression of b(0,+) was higher (P < 0.01) in jejunum but lower (P < 0.01) in the liver of pigs fed the F-AA diet; CAT-1 tended to be lower in liver but higher in LM of PB-AA pigs. Myosin expression was not affected. Intestinal AA absorption was faster in pigs fed the F-AA diet, but AA uptake by the liver seemed to be faster in pigs fed the PB-AA. Performance and expression of AA transporters and myosin suggest that the dietary content of free or protein bound AA does not affect their availability for protein synthesis in pigs. PMID- 24222248 TI - Development and characterization of new microsatellites for walnut (Juglans regia). AB - The expressed sequence tag (EST) database represents a potentially valuable resource for the development of simple sequence repeat (SSR) markers for use in evolutionary studies. EST-SSRs reveal polymorphisms not only within the source taxon, but in related taxa as well. In this paper, we describe a case study in which the publicly available walnut (Juglans regia) EST database was used to develop SSR markers for use in the genetic analysis of the widespread Juglans nigra and Carya cathayensis and an endangered species Annamocarya sinensis. A total of 7262 unigenes, including 1911 contigs and 5351 singletons, were obtained from 13,559 ESTs retrieved from the NCBI database. The 7262 unigenes were further reduced to 706 EST-SSR sequences containing 805 SSR loci. Then, 309 EST-SSR primers were randomly designed, and 77 were identified with five high across species transferability cross-species: namely, J. regia, J. nigra, C. cathayensis, Carya dabieshanensis, and A. sinensis. Thirteen highly polymorphic EST-SSRs were further used for genetic analyses in these above five species. PMID- 24222249 TI - Overexpression, purification, and pharmacologic evaluation of anticancer activity of ribosomal protein L24 from the giant panda (Ailuropoda melanoleuca). AB - The ribosomal protein L24 (RPL24) belongs to the L24E family of ribosomal proteins and is located in the cytoplasm. The purpose of this study was to investigate the structure and anti-cancer function of RPL24 of the giant panda (Ailuropoda melanoleuca). The complementary DNA of RPL24 was cloned successfully using reverse transcription-polymerase chain reaction technology. We constructed a recombinant expression vector containing RPL24 complementary DNA and overexpressed it in Escherichia coli using pET28a plasmids. The expression product obtained was purified using Ni-chelating affinity chromatography. The results indicated that the length of the fragment cloned is 509 bp, and it contains an open-reading frame of 474 bp encoding 157 amino acids. Primary structure analysis revealed that the molecular weight of the putative RPL24 protein is 17.78 kDa with a theoretical isoelectric point of 11.86. The RPL24 gene is readily expressed in E. coli, and the RPL24 fused with the N-terminal histidine-tagged protein to give rise to the accumulation of an expected 23.51 kDa polypeptide. The inhibitory rate in mice treated with 0.1 mg/mL RPL24, the highest of 3 doses administered, can reach 67.662%, which may be comparable to the response to mannatide. The histology of organs with tumors showed that the tissues in the RPL24 group displayed a looser arrangement compared with that in the control group. Furthermore, no obvious damage was apparent in other organs, such as heart, lung, and kidney. The data showed that the recombinant RPL24 had time and dose dependency on the cell growth inhibition rate. Human laryngeal carcinoma Hep-2 cells treated with 0.3125-10 ug/mL RPL24 for 24 h displayed significant cell growth inhibition (P < 0.05; N = 6) in assays using 3-(4,5 dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide compared with that in control (untreated) cells. By contrast, human hepatoma Hep G-2 cells displayed no significant change (P > 0.05; N = 6) from control (untreated) cells. RPL24 has time and dose dependency on Hep-2 cell growth inhibition. The data indicate that the effect at low concentrations is better than that at high concentrations, and the concentration of 0.625 ug/mL provides the best rate of growth inhibition. Further research is ongoing to determine the bioactive principles of recombinant RPL24 protein that are responsible for its anticancer activity. PMID- 24222250 TI - Protein-protein interaction network and significant gene analysis of osteoporosis. AB - This study used DNA microarray data to identify differentially expressed genes of osteoporosis and provide useful information for treatments of the disease. We downloaded gene expression data of Osteoporosis GSE35956 from the Gene Expression Omnibus database, which included five normal and five osteoporosis samples. We then identified the differentially expressed genes between normal and disease samples using the R language software, and constructed the protein interaction network. DAVID was used to perform the biological process enrichment and KEGG pathway cluster analyses. We used the Cytoscape plug-in unit, Cluster ONE, to perform cluster module analysis to find hub proteins of the network module and to analyze their Gene Ontology (GO) functions. A total of 294 genes were found to be differentially expressed between normal and disease samples, which were used to construct the differential gene-protein interaction network. GO function analysis revealed that the genes' functions were mainly involved in the intracellular signaling cascade. KEGG pathway analysis suggested that the main metabolic pathways of these genes were those of cancer: the neurotrophin/T cell/Fc epsilon RI/B cell/ ErbB/p53 signaling pathway, the cell cycle pathway, and the chronic myeloid leukemia pathway. Screening analysis of hub proteins revealed that KRT18 had the highest hub degree. In conclusion, we found differentially expressed genes related to osteoporosis. GO biological process enrichment and KEGG pathway enrichment analyses identified significant osteoporosis genes and their molecular functions. Finally, module analysis of hub proteins in interaction networks showed that cell death was one of the main biological processes of osteoporosis genes. PMID- 24222251 TI - Using PCR-RFLP for sexing of the endangered Galapagos petrel (Pterodroma phaeopygia). AB - Pterodroma phaeopygia is a critically endangered avian species of the Galapagos Islands. This bird is sexually monomorphic, making it difficult to identify the sex. This information, however, is relevant to studies of behavior, ecology, and management of wild or captive populations. Here, we aimed to implement a molecular approach for determining sex in this petrel. DNA was extracted from the blood and the feathers of 24 adult P. phaeopygia, with samples from a female and a male Gallus gallus for comparison. We amplified the cromo-helicase DNA binding protein 1 (CHD-1) gene by PCR, using primers P2 and P8. Allele CHD-1W is unique to females and CHD-1Z occurs in both sexes. We then digested these PCR products using the restriction enzyme HaeIII. The PCR amplified a 400-bp product for both alleles. The digestion of the G. gallus, amplicons split the CHD-1Z allele into two fragments (of 320 and 80 bp), while CHD-1W remained intact. Thus, the male exhibited two bands (digested CHD- 1Z) and the female three bands (undigested CHD 1W and digested CHD-1Z). Applying this RFLP method on DNA derived from blood, 9 of the 24 petrels were found to be male, while 15 were females. The same results were obtained using feathers as the source of DNA. To our knowledge, this is the first report of molecular method for sexing this species. The potential of sexing this petrel from feathers is remarkable as it minimizes blood sampling induced stress. This method could be used to reinforce the conservation efforts for this bird, to investigate population sex ratios and to develop new conservation strategies. PMID- 24222252 TI - Association of insulin growth factor-1 receptor gene polymorphisms with genetic susceptibility to idiopathic short stature. AB - The association between single nucleotide polymorphisms (SNPs) in the insulin like growth factor-1 receptor (IGF-1R) gene and susceptibility to idiopathic short stature (ISS) was investigated. Seven hundred and twelve Chinese children clinically diagnosed with ISS and 575 normal individuals were recruited between 2008 and 2011, and their SNPs were genotyped. Preliminary screening revealed that the rs1976667 and rs2684788 loci were significantly associated with genetic susceptibility to ISS (P = 0.03636 and P = 0.01352, respectively). Stratification by sex revealed that in males, different genotypes at the rs1976667 locus were significantly associated with genetic susceptibility to ISS (P = 0.047), showing G dominant inheritance (P = 0.018). The G allele at the rs2684788 locus was significantly associated with genetic susceptibility to ISS (P = 0.016), showing G dominant inheritance (P < 0.001). In females, different genotypes at the rs1976667 locus were significantly associated with genetic susceptibility to ISS (P = 0.011), showing G dominant inheritance (P = 0.005). Different genotypes at the rs2684788 locus, the G allele, and the G recessive mode of inheritance were all significantly associated with genetic susceptibility to ISS (P < 0.005). The genotypes at the rs1976667 locus in the female ISS group were significantly correlated to IGF-1 standard deviation integral value (SDS) (P = 0.006). The rs1976667 and rs2684788 loci of the human IGF-1R gene are likely associated with different genetic susceptibilities to ISS in males and females. Different clinical phenotypes of ISS may be associated with SNPs of IGF-1R. PMID- 24222253 TI - Relationship between genetic parameters in maize (Zea mays) with seedling growth parameters under 40-100% soil moisture conditions. AB - We estimated the association of genetic parameters with production characters in 64 maize (Zea mays) genotypes in a green house in soil with 40-100% moisture levels (percent of soil moisture capacity). To identify the major parameters that account for variation among the genotypes, we used single linkage cluster analysis and principle component analysis. Ten plant characters were measured. The first two, four, three, and again three components, with eigen values > 1 contributed 75.05, 80.11, 68.67, and 75.87% of the variability among the genotypes under the different moisture levels, i.e., 40, 60, 80, and 100%, respectively. Other principal components (3-10, 5-10, and 4-10) had eigen values less than 1. The highest estimates of heritability were found for root fresh weight, root volume (0.99), and shoot fresh weight (0.995) in 40% soil moisture. Values of genetic advance ranged from 23.4024 for SR at 40% soil moisture to 0.2538 for shoot dry weight in 60% soil moisture. The high magnitude of broad sense heritability provides evidence that these plant characters are under the control of additive genetic effects. This indicates that selection should lead to fast genetic improvement of the material. The superior agronomic types that we identified may be exploited for genetic potential to improve yield potential of the maize crop. PMID- 24222254 TI - A novel SCAR marker for detecting Psathyrostachys huashanica Keng chromatin introduced in wheat. AB - In this study, we cloned and sequenced a 938-base pair polymorphic band, pHs27, in the tightly linked random amplified polymorphic DNA marker OPU10 and converted it into a sequence-characterized amplified region (SCAR) marker referred to as RHS141, which was specific for the Ns genome of Psathyrostachys huashanica. A GenBank basic local alignment search tool search showed that the sequence of pHs27 had no primary sequence homology with known sequences, and Southern blotting confirmed this result. This SCAR marker was used to detect Ns genome chromatin in wheat, and it was successfully amplified in P. huashanica itself, a complete set of wheat-P. huashanica disomic addition lines (1Ns-7Ns), and undetermined homoeologous group addition lines. This SCAR marker will be a powerful tool for the marker-assisted selection of P. huashanica chromosome(s) in a wheat background, and it should also allow wheat breeders to screen for the excellent traits found in P. huashanica chromatin. PMID- 24222255 TI - Cerebroplacental Doppler ratio and placental histopathological features in pregnancies complicated by fetal growth restriction. AB - OBJECTIVE: To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). STUDY DESIGN: A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). RESULTS: The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9+/ 3.6 weeks, 1552+/-561 g, and 1.33+/-0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR]=3.14; 95% confidence intervals [CI]=1.58-6.28, P=0.001), mural hypertrophy (OR=2.35; 95% CI=1.26-4.4, P=0.008), immature intermediate trophoblast (OR=2.0; 95% CI=1.07-3.71, P=0.03) and maternal vascular underperfusion (OR=2.32; 95% CI=1.25-4.23, P=0.007) were the only parameters associated with severity of CPR. CONCLUSIONS: The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance. PMID- 24222256 TI - Impact of sex on perinatal mortality and morbidity in twins. AB - OBJECTIVE: Twin studies offer opportunities to investigate mechanisms underlying sex-associated differences in perinatal outcomes. The objective of the study was to investigate sex-related differences in perinatal complications. STUDY DESIGN: A cohort of 16,045 twin pregnancies - 32,090 twins - was explored for obstetric complications, perinatal and infant mortality, and neonatal morbidities. RESULTS: Twin pregnancies with a female fetus had an increased risk for preeclampsia, but otherwise there were no pregnancy complications associated with fetal sex. After birth, female-female twins had lower early neonatal and infant mortality, and lower risk for respiratory morbidities than male-male twins at all gestational ages. In unlike-sexed twin pairs, very preterm males had higher respiratory morbidity than females and, females were at higher risk for being growth restricted. CONCLUSION: Male-male twins have higher respiratory morbidity and neonatal mortality than female-female twins. In unliked-sexed twin pairs, the males seem to be protected by having a female co-twin. PMID- 24222257 TI - Placental syndecan-1 and sulphated glycosaminoglycans are decreased in preeclampsia. AB - Glycosaminoglycans are found in extracellular matrix and on the cell surface in the form of proteoglycans. There is evidence that these molecules regulate biological processes, including cell survival, migration and angiogenesis. Preeclampsia is a common pregnancy disorder associated with insufficient placental development. This study aimed to determine the concentrations of glycosaminoglycans and the proteoglycan syndecan-1 within villous trophoblast and to investigate changes associated with preeclampsia. Seventy-five placental samples collected from third trimester singleton pregnancies were divided into term placentas following labour onset, gestational age-matched placentas prior to labour onset and preterm placentas. Preterm placentas were divided into three gestational age-matched groups, spontaneous preterm labour, preterm premature rupture of membranes (PPROM) and preterm preeclampsia. Sulphated glycosaminoglycan (sGAG) concentrations in placental extracts were quantified using a modified 1,9-dimethylmethylene blue assay. Syndecan-1 expression was localised using immunohistochemistry and concentrations in placental extracts determined by immunoassay. Preterm placentas had significantly lower sGAG concentrations compared to term tissues and concentrations were significantly lower in preeclampsia compared to spontaneous preterm labour (medians 5.80 and 10.0 MUg/mg protein respectively, P<0.05). Syndecan-1 expression was localised to syncytiotrophoblast and median concentrations were lower in preeclampsia compared to PPROM material (preeclampsia median = 41.7, PPROM 74.4 ng/mg tissue) but not significantly different to concentrations in spontaneous preterm labour. Multivariate analysis revealed that decreased sGAG and syndecan-1 in preeclampsia were independent of labour, gestational age and birthweight centile. These findings may provide insights into a role for these molecules in the pathophysiology of preeclampsia. PMID- 24222258 TI - Hearing impairment in Estonia: an algorithm to investigate genetic causes in pediatric patients. AB - PURPOSE: The present study was initiated to establish the etiological causes of early onset hearing loss (HL) among Estonian children between 2000-2009. METHODS: The study group consisted of 233 probands who were first tested with an arrayed primer extension assay, which covers 199 mutations in 7 genes (GJB2, GJB6, GJB3, SLC26A4, SLC26A5 genes, and two mitochondrial genes - 12S rRNA, tRNASer(UCN)). From probands whose etiology of HL remained unknown, DNA analysis of congenital cytomegalovirus (CMV) infection and G-banded karyotype and/or chromosomal microarray analysis (CMA) were performed. RESULTS: In 110 (47%) cases, the etiology of HL was genetic and in 5 (2%) congenital CMV infection was diagnosed. We found mutations with clinical significance in GJB2 (100 children, 43%) and in 2 mitochondrial genes (2 patients, 1%). A single mutation in SLC26A4 gene was detected in 5 probands (2.2%) and was considered diagnostic. In 4 probands a heterozygous IVS2-2A>G change in the SLC26A5 gene was found. We did not find any instances of homozygosity for this splice variant in the probands. CMA identified in 4 probands chromosomal regions with the loss of one allele. In 2 of them we were able to conclude that the found abnormalities are definitely pathogenic (12q13.3-q14.2 and 17q22-23.2 microdeletion), but the pathogenity of 2 other findings (3p26.2 and 1p33 microdeletion) remained unknown. CONCLUSION: This practical diagnostic algorithm confirmed the etiology of early onset HL for 115 Estonian patients (49%). This algorithm may be generalized to other populations for clinical application. PMID- 24222259 TI - Effects of perioperative immunostimulating nutritional therapy on the phagocytic activity of blood platelets in patients with various clinical stages of gastric cancer. AB - PURPOSE: The aim of this study was to evaluate the total blood platelets count, fraction of phagocytizing thrombocytes (PhT%), and phagocytic index of thrombocytes (PhIT) in gastric cancer considering the stage of the disease, and perioperative immunonutrition support. METHODS: Our study included 44 patients operated for gastric cancer divided into 2 groups depending on the clinical stage, and 40 healthy volunteers -a control group. Group I included 18 patients with stage I-III locoregional malignancies and Group II included 26 patients with stage IV peritoneal dissemination. All patients received immunonutrition during the perioperative period. The phagocytic activity of blood platelets was assessed by measuring PhT% and PhIT prior to and after nutritional therapy. RESULTS: In Group I, the pre-treatment PhT% and PhIT amounted to 1.08 and 0.99, respectively, and 1.26, and 1.1 after the therapy (p<0.01). In Group II, pre-treatment PhT% and PhIT were 1.12 and 0.97, after 1.18 and 1.06, respectively (p<0.05). In the controls, PhT% and PhIT were 2.26 and 1.83, respectively, significantly higher comparing to gastric cancer patients (p<0.01). CONCLUSION: Severe impairment of the thrombocyte phagocytic activity in gastric cancer patients has been found. Phagocytic activity of blood platelets was partially improved as a result of perioperative immunonutrition both in locoregional disease and in peritoneal dissemination. PMID- 24222260 TI - The effect of attenuating noradrenergic neurotransmission by clonidine on brain activity measures of visuospatial attention. AB - OBJECTIVE: In the current study, we investigated the role of noradrenaline in directing (bias) and disengagement of visuospatial attention. METHODS: We assessed the effect of clonidine on event-related brain potential (ERP) reflections of bias and disengagement in a double-blind placebo-controlled crossover design. An initial dose of 200-MUg clonidine was replaced by 100 MUg because of marked side effects. Twenty-one healthy male participants performed the visual-spatial cueing task while an electroencephalogram (EEG) was recorded. The behavioral output is the validity effect (benefit of cueing in terms of reaction time to targets). ERP indices for bias were the cue-related early directing attention negativity and late directing attention positivity, and the target-elicited P1 and N1 modulations by validity ('validity-effect'). The ERP index for disengagement was the target-elicited 'late positive deflection' modulation by validity. Behavioral analyses were performed on 16 participants, electrophysiological analyses on a subset (n=9). RESULTS: Clonidine attenuated the N1 effect, albeit in a subsample. Neither cue-elicited ERPs nor the behavioral validity effect were affected. Clonidine-induced blood pressure reduction was correlated with the reduction of the late positive deflection effect under clonidine. CONCLUSION: Clonidine attenuated the result of bias in a subsample and may have a modulating effect on disengagement. PMID- 24222261 TI - A single gunshot wound of the face with simultaneous aspiration and ingestion of two bullets. PMID- 24222262 TI - Strategies for ventilation in acute, severe lung injury after combat trauma. AB - Post-traumatic Acute Respiratory Distress Syndrome (ARDS) continues to be a major critical care challenge with a high associated mortality and extensive morbidity for those who survive. This paper explores the evolution in recognition and management of this condition and makes some recommendations for treatment of post combat ARDS for military practitioners. It is aimed at the generalist in disciplines other than critical care, but will also be of interest to intensivists. PMID- 24222263 TI - Palladium-catalyzed asymmetric hydrogenolysis of N-sulfonyl aminoalcohols via achiral enesulfonamide intermediates. PMID- 24222264 TI - N-oxide as a traceless oxidizing directing group: mild rhodium(III)-catalyzed C-H olefination for the synthesis of ortho-alkenylated tertiary anilines. AB - Double role: A traceless directing group also acts as an internal oxidant in a novel Rh(III) -catalyzed protocol developed for the synthesis of ortho alkenylated tertiary anilines. A five-membered cyclometalated Rh(III) complex is proposed as a plausible intermediate and confirmed by X-ray crystallographic analysis. PMID- 24222265 TI - Recent developments in the treatment of familial hypercholesterolemia: a review of several new drug classes. AB - OPINION STATEMENT: Familial hypercholesterolemia is a genetic disorder of the low density lipoprotein cholesterol (LDL-c) receptor leading to severe elevations in plasma levels of LDL-c which results in premature atherosclerosis and cardiovascular events. Statins, ezetimibe, and bile acid sequestrants significantly lower LDL-c levels in these patients and subsequently markedly improve survival; however, even with these interventions LDL-c goals often are not met. Several new drug classes are in development and have the potential to make reaching these cholesterol goals easier. In this article we review the most recent trials of several classes of drugs with the potential to change the future of familial hypercholesterolemia management: microsomal triglyceride transfer protein (MTP) inhibitors, apolipoprotein B synthesis inhibitors (mipomersen), cholesterol ester transfer protein (CETP) inhibitors and inhibitors of pro protein convertase subtilisin/kexin 9 (PCSK9). Each class has shown promise with regard to their effects on the lipid profile. However, the potential side-effects of each drug are also being determined and have limited the development of certain agents. Therefore, the long-term effects of these drug classes, both in terms of side-effects and their effect on clinical outcomes such as cardiovascular events and mortality, continue to be determined. PMID- 24222266 TI - Trade-offs in visual processing for stimuli near the hands. AB - It is known that stimuli near the hands receive preferential processing. In the present study, we explored changes in early vision near the hands. Participants were more sensitive to low-spatial-frequency information and less sensitive to high-spatial-frequency information for stimuli presented close to the hands. This pattern suggests enhanced processing in the magnocellular visual pathway for such stimuli, and impaired processing in the parvocellular pathway. Consistent with that possibility, we found that the effects of hand proximity in several tasks were eliminated by illumination with red diffuse light-a manipulation known to impair magnocellular processing. These results help clarify how the hands affect vision. PMID- 24222267 TI - A review of the advancements in probiotic delivery: Conventional vs. non conventional formulations for intestinal flora supplementation. AB - Probiotic delivery systems are widely used nutraceutical products for the supplementation of natural intestinal flora. These delivery systems vary greatly in effectiveness to exert health benefits for a patient. Probiotic delivery systems can be categorized into conventional, pharmaceutical formulations, and non-conventional, mainly commercial food-based, products. The degree of health benefits provided by these probiotic formulations varies in their ability to deliver viable, functional bacteria in large enough numbers (effectiveness), to provide protection against the harsh effects of the gastric environment and intestinal bile (in vivo protection), and to survive formulation processes (viability). This review discusses the effectiveness of these probiotic delivery systems to deliver viable functional bacteria focusing on the ability to protect the encapsulated probiotics during formulation process as well as against harsh physiological conditions through formulation enhancements using coatings and polymer enhancements. A brief overview on the health benefits of probiotics, current formulation, patient and legal issues facing probiotic delivery, and possible recommendations for the enhanced delivery of probiotic bacteria are also provided. Newer advanced in vitro analyses that can accurately determine the effectiveness of a probiotic formulation are also discussed with an ideal probiotic delivery system hypothesized through a combination of the two probiotic delivery systems described. PMID- 24222268 TI - Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants. AB - The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 +/- 0.005 MUgcm(-2)h(-1)) compared with lower concentration (0.029 +/- 0.007 MUgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS. PMID- 24222269 TI - Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery. AB - Push-pull osmotic pump (PPOP) tablets of a practically insoluble model drug were developed and the effect of various formulation and process parameters on tablet performance was evaluated in order to identify critical factors. The formulation factors such as the viscosity grade of polyethylene oxide as the primary polymer as well as the level and location of osmogen within the bilayer tablets led to a difference in performance of osmotic tablets and hence should be critically evaluated in the design of such dosage forms. Modification of granulation process, i.e., the granulating liquid composition or drying method of granules, did not impact the drug release from the osmotic tablets at the evaluated scale of this study. The influence of varying dose and aqueous solubility of other model drugs (i.e., theophylline, acetaminophen, and verapamil HCl) on the developed PPOP template was also investigated. Results showed that irrespective of the perceived complexity of development and manufacturing of osmotic pumps, the osmotic tablets in this study demonstrated a robust and yet flexible platform in accommodating different types of drug candidates, regardless of solubility, for the dose levels below 25% w/w of the pull layer formulation. PMID- 24222270 TI - Formulation and optimization of nonionic surfactants emulsified nimesulide-loaded PLGA-based nanoparticles by design of experiments. AB - This investigation aimed to develop nimesulide (NMS)-loaded poly(lactic-co glycolic acid) (PLGA)-based nanoparticulate formulations as a biodegradable polymeric drug carrier to treat rheumatoid arthritis. Polymeric nanoparticles (NPs) were prepared with two different nonionic surfactants, vitamin E d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and poly(vinyl alcohol) (PVA), using an ultrasonication solvent evaporation technique. Nine batches were formulated for each surfactant using a 3(2) factorial design for optimal concentration of the emulsifying agents, 0.03-0.09% for vitamin E TPGS and 2-4% for PVA. The surfactant percentage and the drug/polymer ratio (1:10, 1:15, 1:20) of the NMS-loaded NPs were investigated based on four responses: encapsulation efficiency, particle size, the polydispersity index, and the surface charge. The response surface plots and linearity curves indicated a relationship between the experiment's responses and a set of independent variables. The NPs produced with both surfactants exhibited a negative surface charge, and scanning electron micrographs revealed that all of the NPs were spherical in shape. A narrower size distribution and higher drug loadings were achieved in PVA-emulsified PLGA NPs than in the vitamin E TPGS emulsified. Decreasing amounts of both nonionic surfactants resulted in a reduction in the emulsion's viscosity, which led to a decrease in the particle size of NPs. According to the ANOVA results obtained in this present research, vitamin E TPGS exhibited the best correlation between the independent variables, namely drug/polymer ratio and the surfactant percentage, and the dependent variables (encapsulation efficiency R(2) = 0.9603, particle size R(2) = 0.9965, size distribution R(2) = 0.9899, and surface charge R(2) = 0.8969) compared with PVA. PMID- 24222271 TI - Ultrastructural and three-dimensional study of post-LASIK ectasia cornea. AB - INTRODUCTION: Post-laser in situ keratomileusis (LASIK) corneal ectasia is a serious late postoperative complication. Here, we report the ultrastructural features of the post-LASIK cornea of two patients. METHODS: Two normal corneas (age 24 and 37 years old) and two post-LASIK ectaic corneas from two patients (A and B) were studied. The "patient A" (age 27 years) underwent penetrating keratoplasty and "patient B" (age 31 years) underwent deep-anterior lamellar keratoplasty. The excised corneas were processed for light and electron microscopy. A total of 120 images for three-dimensional (3D) reconstruction were taken by using the software "Recorder" and using a bottom mounted camera "Quemesa" attached to a JOEL 1400 transmission electron microscope. The 3D images were constructed using "Visual Kai" software. RESULTS: In the post-LASIK cornea, the hemidesmosomes, the basement membrane, and Bowman"s layer were abnormal. The stromal lamellae were thin and disorganized. The collagen fibrils (CFs) diameter and interfibrillar spacing had decreased. Aggregated microfibrils were present in the Bowman's layer and all parts of the stroma. A large number of microfilaments were present at the detachment end of the flap and residual stroma. The 3D images showed the presence of collagen microfibrils and proteoglycans (PGs) within the CF of the normal and post-LASIK cornea. The collagen microfibrils and PGs within the CFs had degenerated in the post-LASIK cornea. CONCLUSION: Collagen microfibrils and PGs within the CFs were degenerated, leading to the degeneration of CFs, followed by the disorganization of lamellae in post-LASIK cornea. The CFs diameter and interfibrillar spacing decreased. PMID- 24222272 TI - Effects of rare earth ions (Tb, Ce, Eu, Dy) on the thermoluminescence characteristics of sol-gel derived and gamma-irradiated SiO2 nanoparticles. AB - Highly pure SiO2 and SiO2 :RE nanoparticles were synthesized by the sol-gel method. The morphological, structural and optical properties of the nanoparticles were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). XRD results indicate that all the samples studied were free from impurities. SEM/TEM results indicate that the samples were well dispersed. Surface characterization of the nanocrystals by Fourier transform infrared spectroscopy has been carried out and the structure of surface-bound SiO2 based on spectral analysis is proposed. Thermoluminescence (TL) characteristics were investigated to study the influence of rare earth dopants (Tb, Ce, Eu, Dy) on SiO2 matrix subjected to 0.5 kG (1 h) gamma irradiation. Among these rare earth elements, Eu(3+) was found to be the most efficient dopant for SiO2 showing maximum thermoluminescence intensity. SiO2 :Eu0.5 seems to be a promising candidate for use as a TL dosimeter. PMID- 24222273 TI - Balloon laryngoplasty for pediatric laryngeal stenosis: case series and systematic review. AB - OBJECTIVES/HYPOTHESIS: The aim of this study was to systematically review available literature on the outcomes of children treated with balloon laryngoplasty (BLP) as a primary or adjuvant treatment for subglottic or laryngeal stenosis, as well as briefly report on a new series of 60 children treated at the Medical University of South Carolina from 2007 to 2013. STUDY DESIGN: Review of published case series and retrospective chart review. METHODS: A literature search was performed in PubMed and MEDLINE to identify trials that reported clinical outcomes of BLP in human patients under the age of 18 with subglottic or laryngeal stenosis. Single case reports and series studying the dilation of tracheal or bronchial stenosis alone were excluded. Hospital billing codes were used to identify appropriate patients for retrospective chart review. A successful outcome for chart review was determined to be decannulation of previous tracheostomy or avoidance of open laryngotracheoplasty or tracheostomy. RESULTS: Seven studies published between 1991 and 2012 met inclusion criteria and reported outcomes with success defined through improvement of symptoms, decrease in Myer-Cotton level of stenosis, decannulation, or avoidance of reconstructive procedures. Including 60 children from our institution, 202 patients between 1 day and 22 years of age (average 35 months) underwent 457 dilations, with an average of 2.26 dilations per patient (2.25 in our population). The overall success rate was 64% (77% in our population). No complications were reported with subglottic or laryngeal dilations. CONCLUSIONS: BLP is a highly effective, low risk alternative or adjunct to traditional reconstructive procedures in children with subglottic or laryngeal stenosis. LEVEL OF EVIDENCE: 4. PMID- 24222274 TI - The 5-HTTLPR polymorphism and posttraumatic stress disorder: a meta-analysis. AB - Environmental and genetic factors contribute to the development of posttraumatic stress disorder (PTSD). Variation in the 5-HTTLPR polymorphism of the serotonin transporter gene has been hypothesized to affect risk for PTSD. With the aim of investigating this association, we conducted a meta-analysis to shed light on prior controversial results and increase statistical power to detect smaller effect sizes. PubMed and ISI databases were searched for studies published until December 2012. Twelve studies have been included, all based on trauma-exposed samples. Data were analyzed with Cochrane Collaboration Review Manager Software (Version 5). Quality and publication bias were assessed. Metaregressions were performed using Comprehensive Meta-Analysis software, Version 2. Taking into account all studies, no association was found between 5-HTTLPR and PTSD (p = .10), with evidence of between-study heterogeneity, which could be partly explained by gender differences. In sensitivity analyses, we found an association between SS genotype and PTSD in high trauma-exposed participants (p < .001). To be a carrier of the SS genotype seems to represent a risk factor for PTSD in high trauma exposure. Further studies focusing on Gene * Environment interactions are needed to better understand the role of this polymorphism in PTSD. PMID- 24222275 TI - Mechanisms of antitumor and immune-enhancing activities of MUC1/sec, a secreted form of mucin-1. AB - Mucin 1 (MUC1) is a polymorphic type 1 transmembrane protein found on the apical surface of normal cells lining the lumen of ducts and glands. Mucins are thought to provide mucosal protection from environmental exposures and carcinogens. An altered form of the MUC1 glycoprotein, which is hypoglycosylated, is expressed in several types of human cancers. In our laboratory, we have found that transfection of a murine mammary tumor cell line with a human secreted isoform of MUC1 rendered these DA-3 cells (DA-3/sec) incapable of growing in intact BALB/c mice. In contrast, implantation of DA-3 cells transfected with the human transmembrane isoform of MUC1 (DA-3/TM), resulted in tumor formation and ultimately death of the animals, similar to the DA-3 parental line. Importantly, inoculation of the DA-3/sec cells in immunodeficient nude mice resulted in tumor formation, indicating that the MUC1/sec molecule's antitumor activity is immunologically controlled. In this review, we summarize the studies we have performed to elucidate possible mechanisms for the immune-mediated antitumor effect of MUC1/sec and/or a unique peptide present in this mucin. Understanding these mechanisms may provide new immunotherapeutic approaches that could be used to target different types of cancer. PMID- 24222276 TI - CHI3L1 plays a role in cancer through enhanced production of pro-inflammatory/pro tumorigenic and angiogenic factors. AB - Elevated serum levels of a glycoprotein known as chitinase-3-like protein 1 (CHI3L1) have been correlated with poor prognosis and shorter survival of patients with cancer and inflammatory diseases. The biological and physiological functions of CHI3L1 in cancer have not yet been completely elucidated. In this review, we describe the role of CHI3L1 in inducing pro-inflammatory/pro tumorigenic and angiogenic factors that could promote tumor growth and metastasis. PMID- 24222277 TI - Semaphorin7A: branching beyond axonal guidance and into immunity. AB - Semaphorins are a family of proteins that were originally described for their role in axonal guidance. Studies now show that semaphorins encompass many physiological functions outside of the nervous system, including immune responses. Semaphorin7A (SEMA7A) belongs to the "immune" semaphorin group and has been shown to play a crucial role in regulating immune responses. In this review, we discuss the structure and function of SEMA7A as well as its role in innate and adaptive immunity [corrected].We further describe SEMA7A's involvement in inflammatory disease and its emergent role in cancer. PMID- 24222278 TI - Pre- and perinatal brain development and enculturation : A biogenetic structural approach. AB - Ample evidence from various quarters indicates that the perceptual-cognitive competence of the pre- and perinatal human being is significantly greater than was once thought. Some of the evidence of this emerging picture of early competence is reviewed, and its importance both as evidence of the biogenetic structural concept of "neurognosis" and for a theory of enculturation is discussed. The literature of pre- and perinatal psychology, especially that of developmental neuropsychology, psychobiology, and social psychophysiology, is incorporated, and some of the implications of these data for a theory of enculturation are suggested. PMID- 24222279 TI - The nature of crime : Is cheating necessary for cooperation? AB - The classical social theorist Emile Durkheim proposed the counterintuitive thesis that crime is beneficial for society because it provokes punishment, which enhances social solidarity. His logic, however, is blemished by a reified view of society that leads to group-selectionist thinking and a teleological account of the causes of crime. Reconceptualization of the relationship between crime and punishment in terms of evolutionary game theory, however, suggests that crime (cheating) may confer benefits on cooperating individuals by promoting stability in their patterns of cooperation. PMID- 24222281 TI - Secular trends in human sex ratios : Their influence on individual and family behavior. AB - Secular change in sex ratios is examined in relation to experience in the family. Two theoretical perspectives are outlined: Guttentag and Secord's (1983) adaptation of social exchange theory, and sexual selection theory. Because of large-scale change in number of births and typical age differentials between men and women at marriage, low sex ratios at couple formation ages existed in the U.S. between 1965 and the early 1980s. The currently high sex ratios, however, will persist until the end of the century. High sex ratios appear to be associated with lower divorce rates, male commitment to careers that promise economic rewards, male willingness to engage in child care, higher fertility, and higher rates of sexual violence. Sexual selection theory calls attention to intrasexual competition in the numerically larger sex. PMID- 24222280 TI - Ingestion and emotional health. AB - Evidence abounds of a close relation between ingestive and affective processes in rats and in humans. Emotional distress alters food intake and body weight; conversely, alterations in eating and weight influence emotional health. Thorough experimental analysis of the ingestion-affect relation may clarify the mechanisms of anxiety and depression. A strategy is proposed for examination of environmental and dispositional determinants of ingestive processes, emotionality, and responses to stress. PMID- 24222282 TI - IAPs perspectives on current vaccination scenario in India. PMID- 24222284 TI - Recent advances in management of bronchiolitis. AB - BACKGROUND: Bronchiolitis is one of the major causes for hospital admissions in infants. Managing bronchiolitis, both in the outpatient and inpatient setting remains a challenge to the treating pediatrician. The effectiveness of various interventions used for infants with bronchiolitis remains unclear. NEED AND PURPOSE: To evaluate the evidence supporting the use of currently available treatment and preventive strategies for infants with bronchiolitis and to provide practical guidelines to the practitioners managing children with bronchiolitis. METHODS: A search of articles published on bronchiolitis was performed using PubMed. The areas of focus were diagnosis, treatment and prevention of bronchiolitis in children. Relevant information was extracted from English language studies published over the last 20 years. In addition, the Cochrane Database of Systematic Reviews was searched. RESULTS AND CONCLUSIONS: Supportive care, comprising of taking care of oxygenation and hydration, remains the corner stone of therapy in bronchiolitis. Pulse oximetry helps in guiding the need for oxygen administration. Several recent evidence-based reviews have suggested that bronchodilators or corticosteroids lack efficacy in bronchiolitis and should not be routinely used. A number of other novel therapies (such as nebulized hypertonic saline, heliox, CPAP, montelukast, surfactant, and inhaled furosemide) have been evaluated in clinical trials, and although most of them did not show any beneficial results, some like hypertonic saline, surfactant, CPAP have shown promising results. PMID- 24222285 TI - Citrullinemia type 1: genetic diagnosis and prenatal diagnosis in subsequent pregnancy. AB - Citrullinemia type 1 was diagnosed by tandem mass spectrometry in a full term male neonate who presented with an acute catastrophic collapse on the 3rd day of life. Both parents were identified to be carriers for the exon 15 p Gly390Arg mutation in the argininosuccinate synthetase gene located at chromosome 9q34.1. Chorionic villus sampling and prenatal genetic testing in the subsequent pregnancy revealed an affected fetus resulting in termination of pregnancy. PMID- 24222286 TI - Crossed polydactyly and Greig cephalopolysyndactyly syndrome. AB - Greig cephalopolysyndactyly syndrome is a rare genetic disorder, with an autosomal dominant inheritance and consisting of a triad of polysyndactyly, macrocephaly and hypertelorism. Crossed polydactyly is a finding characteristically associated with this syndrome. We report a one and half year old male child who presented with classic clinical features and family history diagnostic of the above syndrome. PMID- 24222287 TI - Atypical subacute sclerosing panencephalitis with short onset latency. PMID- 24222288 TI - Cholera-like illness due to Aeromonas caviae. PMID- 24222289 TI - Role of zinc in neonatal sepsis: emerging data. PMID- 24222290 TI - Congenital scaphoid megalourethra. PMID- 24222291 TI - N-acetyl cysteine in non-acetaminophen pediatric acute liver failure: recent evidence! PMID- 24222292 TI - Should N-acetylcysteine be used in treatment of non-acetaminophen pediatric acute liver failure? PMID- 24222293 TI - Reversible skin hyperpigmentation in Imerslund-Grasbeck syndrome. PMID- 24222294 TI - Status of primary immunodeficiency disorders in India. PMID- 24222295 TI - Diffuse non-epidermolytic palmoplantar keratoderma. PMID- 24222296 TI - Reticulate acropigmentation of Kitamura. PMID- 24222297 TI - Unilateral linear porokeratosis. PMID- 24222298 TI - Black heel (talon noir) associated with a viral exanthem. PMID- 24222299 TI - Is handheld optical coherence tomography reliable in infants and young children with and without nystagmus? AB - PURPOSE: To evaluate the reliability of the spectral domain handheld OCT (HH-OCT) in assessing foveal morphology in children with and without nystagmus. METHODS: Forty-nine subjects with nystagmus (mean age 43.83 months; range, 1-82 months) and 48 controls (mean age 43.02 months; range, 0 to 83 months) were recruited and scanned using HH-OCT. A minimum of two separate volumetric scans on the same examination day of the fovea were obtained. The images were imported into ImageJ software where manual retinal layer segmentation of the central foveal B-scan was performed. Agreement between scans was assessed by determining the intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: Both the nystagmus and control groups showed an excellent degree of reproducibility between two examinations with ICCs greater than 0.96 for central macular thickness (CMT) and greater than 0.8 for the outer nuclear layer and outer segment of the photoreceptors. The nerve fiber layer, ganglion cell layer, outer plexiform layer, inner segment of the photoreceptors, and retinal pigment epithelium were less reliable with ICCs of less than 0.7. There was no difference in the reliability of scans obtained in children with nystagmus as compared with controls and both groups had good intereye agreement with ICCs greater than 0.94 for CMT. CONCLUSIONS: We have shown for the first time that the HH-OCT provides reliable measurements in children with and without nystagmus. This is important, as the HH-OCT will have a greater diagnostic and prognostic role in young children with nystagmus and other eye diseases in the future. PMID- 24222300 TI - Enzymatic degradation identifies components responsible for the structural properties of the vitreous body. AB - PURPOSE: Vitreous degeneration contributes to several age-related eye diseases, including retinal detachment, macular hole, macular traction syndrome, and nuclear cataracts. Remarkably little is understood about the molecular interactions responsible for maintaining vitreous structure. The purpose of this study was to measure the structural properties of the vitreous body after enzymatic degradation of selected macromolecules. METHODS: Mechanical properties of plugs of bovine and porcine vitreous were analyzed using a rheometer. Oscillatory and extensional tests measured vitreous stiffness and adhesivity, respectively. Major structural components of the vitreous were degraded by incubation overnight in collagenase, trypsin, or hyaluronidase, singly or in combination. Vitreous bodies were also incubated in hyper- or hypotonic saline. Effects of these treatments on the mechanical properties of the vitreous were measured by rheometry. RESULTS: Enzymatic digestion of each class of macromolecules decreased the stiffness of bovine vitreous by approximately half (P < 0.05). Differential effects were observed on the damping capacity of the vitreous (P < 0.05), which was shown to correlate with material behavior in extension (P < 0.01). Digestion of hyaluronan significantly decreased the damping capacity of the vitreous and increased adhesivity. Collagen degradation resulted in the opposite effect, whereas digestion of proteins and proteoglycans with trypsin did not alter behavior relative to controls. Osmotic perturbations and double-enzyme treatments further implicated hyaluronan and hyaluronan-associated water as a primary regulator of adhesivity and material behavior in extension. CONCLUSIONS: Collagen, hyaluronan, and proteoglycans act synergistically to maintain vitreous stiffness. Hyaluronan is a key mediator of vitreous adhesivity, and mechanical damping is an important factor influencing dynamic vitreous behavior. PMID- 24222301 TI - Further insights into GPR179: expression, localization, and associated pathogenic mechanisms leading to complete congenital stationary night blindness. AB - PURPOSE: Mutations in GPR179, which encodes the G protein-coupled receptor 179, lead to autosomal recessive complete (c) congenital stationary night blindness (CSNB), which is characterized by an ON-bipolar retinal cell dysfunction. This study further defined the exact site of Gpr179 expression and its protein localization in human retina and elucidated the pathogenic mechanism of the reported missense and splice site mutations. METHODS: RNA in situ hybridization was performed with mouse retinal sections. A commercially available antibody was validated with GPR179-overexpressing COS-1 cells and applied to human retinal sections. Live-cell extracellular staining along with subsequent intracellular immunolocalization and ELISA studies were performed using mammalian cells overexpressing wild-type or missense mutated GPR179. Wild-type and splice site mutated mini-gene constructs were transiently transfected, and RNA was extracted. RT-PCR-amplified products were cloned, and Sanger sequenced. RESULTS: Mouse Gpr179 transcript was expressed in the upper part of the inner nuclear layer, and the respective human protein localized at the dendritic tips of bipolar cells in human retina. The missense mutations p.Tyr220Cys, p.Gly455Asp, and p.His603Tyr led to severely reduced cell surface localization, whereas p.Asp126His did not. The mutated splice donor site altered GPR179 splicing. CONCLUSIONS: Our findings indicate that the site of expression and protein localization of human and mouse GPR179 is similar to that of other proteins implicated in cCSNB. For most of the mutations identified so far, loss of the GPR179 protein function seems to be the underlying pathogenic mechanism leading to this form of cCSNB. PMID- 24222302 TI - A novel color vision test for detection of diabetic macular edema. AB - PURPOSE: To determine the sensitivity of the Seoul National University (SNU) computerized color vision test for detecting diabetic macular edema. METHODS: From May to September 2003, a total of 73 eyes of 73 patients with diabetes mellitus were examined using the SNU computerized color vision test and optical coherence tomography (OCT). Color deficiency was quantified as the total error score on the SNU test and as error scores for each of four color quadrants corresponding to yellows (Q1), greens (Q2), blues (Q3), and reds (Q4). SNU error scores were assessed as a function of OCT foveal thickness and total macular volume (TMV). RESULTS: The error scores in Q1, Q2, Q3, and Q4 measured by the SNU color vision test increased with foveal thickness (P < 0.05), whereas they were not correlated with TMV. Total error scores, the summation of Q1 and Q3, the summation of Q2 and Q4, and blue-yellow (B-Y) error scores were significantly correlated with foveal thickness (P < 0.05), but not with TMV. CONCLUSIONS: The observed correlation between SNU color test error scores and foveal thickness indicates that the SNU test may be useful for detection and monitoring of diabetic macular edema. PMID- 24222303 TI - Absolute retinal blood flow measurement with a dual-beam Doppler optical coherence tomography. AB - PURPOSE: To test the capability of a novel dual-beam Doppler optical coherence tomography (OCT) technique for simultaneous in vivo measurement of the Doppler angle and, thus, the absolute retinal blood velocity and the retinal flow rate, without the influence of motion artifacts. METHODS: A novel dual-beam Doppler spectral domain OCT (SD-OCT) was developed. The two probing beams are separated with a controllable distance along an arbitrary direction, both of which are controlled by two independent 2D optical scanners. Two sets of optical Doppler tomography (ODT) images are acquired simultaneously. The Doppler angle of each blood vessel segment is calculated from the relative coordinates of the centers of the blood vessel in the two corresponding ODT images. The absolute blood flow velocity and the volumetric blood flow rate can then be calculated. To measure the total retinal blood flow, we used a circular scan pattern centered at the optic disc to obtain two sets of concentric OCT/ODT images simultaneously. RESULTS: We imaged two normal human subjects at ages of 48 and 34 years. The total retinal blood flow rates of the two human subjects were calculated to be 47.01 MUL/min (older subject) and 51.37 MUL/min (younger subject), respectively. Results showed that the performance of this imaging system is immune to eye movement, since the two sets of ODT images were acquired simultaneously. CONCLUSIONS: The dual-beam OCT/ODT system is successful in measuring the absolute retinal blood velocity and the volumetric flow rate. The advantage of the technique is that the two sets of ODT images used for the calculation are acquired simultaneously, which eliminates the influence of eye motion and ensures the accuracy of the calculated hemodynamic parameters. PMID- 24222304 TI - Progressive myopia or hyperopia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light. AB - PURPOSE: To determine whether progressive ametropia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light. METHODS: One-day old chicks were raised in red light (90% red, 10% yellow-green) or in blue light (85% blue, 15% green) with a 12 hour on/off cycle for 14 to 42 days. Refraction was determined by streak retinoscopy, and by automated infrared photoretinoscopy and ocular biometry by A-scan ultrasonography. RESULTS: Red light induced progressive myopia (mean refraction +/- SD at 28 days, -2.83 +/- 0.25 diopters [D]). Progressive hyperopia was induced by blue light (mean refraction at 28 days, +4.55 +/- 0.21 D). The difference in refraction between the groups was highly significant at P < 0.001. Induced myopia or hyperopia was axial as confirmed by ultrasound biometry. Myopia induced by 21 days of red light (-2.21 +/- 0.21 D) was reversed to hyperopia (+2.50 +/- 0.29 D) by subsequent 21 days of blue light. Hyperopia induced by 21 days of blue light (+4.21 +/- 0.19 D) was reversed to myopia (-1.23 +/- 0.12 D) by 21 days of red light. CONCLUSIONS: Rearing chicks in red light caused progressive myopia, while rearing in blue light caused progressive hyperopia. Light-induced myopia or hyperopia in chicks can be reversed to hyperopia or myopia, respectively, by an alteration in the chromaticity of ambient light. Manipulation of chromaticity may be applicable to the management of human childhood myopia. PMID- 24222305 TI - Nonneuronal control of the differential distribution of myelin along retinal ganglion cell axons in the mouse. AB - PURPOSE: In most mammalian species, retinal ganglion cell (RGC) axons are myelinated in the optic nerve, but remain nonmyelinated in the retinal nerve fiber layer and the most proximal (i.e., retina-near) region of the nerve. Here we analyzed whether RGCs are involved in the control of this characteristic distribution of oligodendrocytes and myelin in the primary visual pathway of mice. METHODS: Neurospheres were enriched in oligodendrocyte progenitor cells (OPCs) by a short-term exposure to platelet-derived growth factor (PDGF) and grafted into the retina of young postnatal mice close to the optic disc. Immunohistochemistry was performed to study the integration and differentiation of the grafted cells, and the formation of donor-derived myelin in the normally nonmyelinated retinal nerve fiber layer and intrabulbar and most proximal retrobulbar region of the optic nerve. RESULTS: Intraretinal transplantations of small-sized PDGF-treated neurospheres into young postnatal mice resulted in extensive integration of the grafted cells into host retinas. A significant fraction of the donor cells differentiated into oligodendrocytes that myelinated the nerve fiber layer. Importantly, RGC axon segments within the normally nonmyelinated intrabulbar and most proximal retrobulbar region of the nerve also became myelinated in a fraction of animals. CONCLUSIONS: This is the first report demonstrating that the normally nonmyelinated intrabulbar and retrobulbar segments of RGC axons are competent to become myelinated. Results support the view that the differential distribution of myelin and oligodendrocytes in the primary visual pathway is controlled by nonneuronal factors rather than by the RGCs themselves. PMID- 24222306 TI - Corneal staining characteristics in limited zones compared with whole cornea documentation for the detection of dry eye subtypes. AB - PURPOSE: To determine the reliability of single- and double-zone corneal fluorescent staining compared with five-zone analysis for the prediction of dry eye disease. METHODS: Prospective study of 510 subjects with dry eye disease characterized using corneal fluorescein staining, Schirmer scores, and tear break up times. Corneal staining was quantified using Baylor scoring with ROC analysis used to assess predictive power of single- and double-zone compared with five zone analysis for aqueous, evaporative, and mixed dry eye disease. RESULTS: Double-zone analysis predicted each subtype of dry eye disease investigated. Aqueous disease was predicted by superior/inferior zones (AUCSup/Inf 0.797 versus AUCTotal 0.816), evaporative disease by inferior/central zones (AUCInf/Cen 0.759 versus AUCTotal 0.778), and mixed disease by superior/inferior, inferior/nasal, and inferior/central zones (AUCSup/Inf 0.765, AUCInf/Nas 0.771, AUCInf/Cen 0.778 versus AUCTotal 0.795). Inferior zone analysis predicted aqueous (AUCInf 0.751 versus AUCTotal 0.750), evaporative (AUCInf 0.756 versus AUCTotal 0.752), and mixed (AUCInf 0.831 versus AUCTotal 0.788) dry eye disease with similar efficacy to complete analysis in diabetic individuals. Inferior zone analysis also predicted aqueous disease in rheumatoid arthritis patients (AUCInf 0.804 versus AUCTotal 0.785), whereas superior zone analysis predicted evaporative disease in thyroid disease patients (AUCSup 0.765 versus AUCTotal 0.752). CONCLUSIONS: Double-zone corneal staining predicts the presence of dry eye disease with predictive power similar to complete corneal analysis. Additionally, subtypes of dry eye can be predicted by single-zone analysis among patients with diabetes (inferior zone), rheumatoid arthritis (inferior zone), and thyroid disease (superior zone). Clinical characterization of dry eye can thus be hastened by limiting corneal examination to specific zones. PMID- 24222307 TI - Determinants of macular thickness using spectral domain optical coherence tomography in healthy eyes: the Singapore Chinese Eye study. AB - PURPOSE: We determined ocular and systemic factors influencing macular thickness measured by spectral-domain optical coherence tomography (SD-OCT) in a population based sample of healthy eyes. METHODS: We recruited 490 healthy Chinese adults, aged 40 to 80 years, from the Singapore Chinese Eye Study, a population-based survey. All participants underwent a comprehensive eye examination and a standardized interview. The SD-OCT (Cirrus HD-OCT, software version 6.0) was used to measure a range of macular thickness parameters (central foveal subfield thickness, average inner macular thickness, average outer macular thickness, overall average macular thickness, and overall macular cube volume). Linear regression analyses were performed to examine the effects of various ocular and systemic factors on macular thickness. RESULTS: The mean (standard deviation) age of the subjects was 53.17 (6.14) years and 50.0% of them were male. The mean central foveal subfield, average inner, and average outer macular thicknesses were 250.38 (20.58), 319.33 (14.40), and 276.67 (11.94) MUm, respectively. The overall average macular thickness was 280.25 (11.42) MUm and overall macular cube volume was 10.09 (0.41) mm(3). Sex, age, and axial length (AL) are the factors that influenced macular thicknesses. Thinner overall average macular thickness was associated with female sex (4.46 MUm thinner compared to males, P < 0.001), older age (0.38 MUm decrease per each year increase in age, P < 0.001), and longer AL (2.34-MUm decrease per each mm increase in AL, P < 0.001), whereas thinner central foveal subfield thickness was associated with female sex (13.5 MUm thinner compared to males, P < 0.001) and shorter AL (3.33-MUm decrease per each mm increase in AL, P < 0.001). CONCLUSIONS: Female sex, older age, and longer AL were associated independently with thinner overall average macular thickness, whereas female sex and shorter AL were associated with thinner central foveal thickness in ethnic Chinese. These factors should be taken into consideration when interpreting macular thickness measurements with SD-OCT. PMID- 24222308 TI - Stress and visual function in infantile nystagmus syndrome. AB - PURPOSE: Infantile nystagmus syndrome (INS) is an involuntary oscillation of the eyes that has been reported to impair vision and worsen under stress. This investigation aimed to measure visual function in terms of visual acuity (VA) and response time (RT), when INS subjects are placed under stress. METHODS: A total of 23 subjects with INS and 20 control subjects performed a 2-alternative forced choice (2AFC) staircase procedure identifying the gap in a Landolt C, under 4 experimental conditions: initial acclimatization (A); task demand (TD), during which subjects received a small electrical shock for every incorrect answer; anticipatory anxiety (AA), during which subjects received a small shock at random intervals; and relaxed (R). Arousal was monitored with galvanic skin conductance (SkC). In addition to VA and eye movements, RTs were recorded. RESULTS: The SkC was higher in the TD and AA periods and lower during A and R. Shock significantly increased nystagmus amplitude (P < 0.01) and intensity (P < 0.007), and reduced foveation periods (FPs, P < 0.022). In both groups, VA was not reduced, but showed a slight improvement. However, shock increased RT (P < 0.009), and INS subjects were slower than controls (P < 0.0005). CONCLUSIONS: Increased arousal ("stress") provoked more intense nystagmus eye movements. As seen in other studies, stress did not reduce VA despite the shorter FPs. Although VA and FP can correlate across subjects, there would appear to be little correlation, if any, within a subject. However, RTs did increase with stress and shorter FPs, which may have an adverse impact on the visual performance of those with INS. PMID- 24222309 TI - The effect of degrading binocular single vision on fine visuomotor skill task performance. AB - PURPOSE: To evaluate the impact of degrading binocular single vision (BSV) on performance of fine visuomotor skill tasks requiring speed/accuracy. METHODS: Binocular functions (Frisby/Preschool Randot [PSR] stereoacuity, horizontal phasic prism fusion amplitudes) were measured in visually normal participants aged 18 to 40 years (n = 80). Participants performed 2-timed visuomotor tasks: water pouring (450 mL accurately into five measuring cylinders at 90 mL) and bead threading on upright needles (30 large, 22 small beads, creating two difficulty levels). Task and binocular function measures were repeated in a randomized order with monocular visual acuity (VA) reduced in three-line increments using convex spherical lenses. Analyses used were Kruskal-Wallis/Mann-Whitney U tests and linear mixed modeling. RESULTS: Median Frisby stereoacuity levels were 20" arc at baseline, 55" arc when VA was degraded by 6 lines, 210" arc by 9 lines, and unmeasurable by 12 lines (9 lines in some individuals). Task performance times deteriorated for the large bead task (7%-10% between lenses, total 37% from median baseline time of 51 seconds, P < 0.001), and small bead task (0.5%-15% between lenses, total 42% from median baseline time of 57 seconds, P < 0.001). Binocular function measures causing significant fixed effects were base-out fusional amplitudes in both bead tasks (large: P = 0.010, small: P = 0.011) and PSR stereoacuity in the small bead task (P = 0.047). Water-pouring task performance was not significantly affected by changes in any experimental parameter. CONCLUSIONS: Degrading motor fusion as well as stereoacuity significantly affects performance in certain fine visuomotor tasks. This impact is differentially affected by task difficulty. PMID- 24222310 TI - The influence of horizontal convergence on slow oscillatory eye movements during visual fixation. AB - PURPOSE: Slow oscillatory eye movements (SOMs) occur simultaneously with tremor, drifts, and microsaccades during visual fixation. In a previous study, the amplitude of SOM was found to be affected by the visual characteristics of the stimuli. This indicates a perceptual influence on the control of the movement. However, the frequency of SOM did not change. The aim of our study was to investigate how SOM is affected by extraocular muscle tension. METHODS: In a repeated-measurement experiment, 14 subjects were instructed to maintain fixation for 3 minutes on a bright dot presented at four distances (15, 30, 60, and 120 cm). The level of extraocular muscle tension is assumed to increase with decreased fixation distance due to convergence angle. Eye movements were recorded binocularly using a video eye tracker, and the amplitude and frequency of SOM for each eye were obtained by independently filtering the horizontal and vertical eye position signals with a discrete Fourier transformation. RESULTS: The results showed no significant differences for the amplitude. However, the horizontal frequency was found to be significantly lower at the closest distance. No significant differences were found for the vertical frequency. CONCLUSIONS: Based on these findings we conclude that extraocular muscle tension does have an effect on the frequency, but not the amplitude, of the oscillations. The apparent double dissociation between perceptual effects on amplitude versus muscle tension effects on frequency is discussed in relation to the origin and control of SOM. PMID- 24222311 TI - Internal dosimetry estimates using voxelized reference phantoms for thyroid agents. AB - This work presents internal dosimetry estimates for diagnostic procedures performed for thyroid disorders by relevant radiopharmaceuticals. The organ doses for (131)Iodine, (123)Iodine and (99m)Tc incorporated into the body were calculated for the International Commission on Radiological Protection (ICRP) reference voxel phantoms using the Monte Carlo transport method. A comparison between different thyroid uptakes of iodine in the range of 0-55% was made, and the effect of various techniques for administration of (99m)Tc on organ doses was studied. To investigate the necessity of calculating organ dose from all source regions, the major source organ and its contribution to total dose were specified for each target organ. Moreover, we compared effective dose in ICRP voxel phantoms with that in stylized phantoms. In our method, we directly calculated the organ dose without using the S values or SAFs, as is commonly done. Hence, a distribution of the absorbed dose to entire tissues was obtained. The chord length distributions (CLDs) were also computed for the selected source-target pairs to make comparison across the genders. The results showed that the S values for radionuclides in the thyroid are not sufficient for calculating the organ doses, especially for (123)I and (99m)Tc. The thyroid and its neighboring organs receive a greater dose as thyroid uptake increases. Our comparisons also revealed an underestimation of organ doses reported for the stylized phantoms compared with the values based on the ICRP voxel phantoms in the uptake range of 5-55%, and an overestimation of absorbed dose by up to 2-fold for Iodine administration using blocking agent and for (99m)Tc incorporation. PMID- 24222312 TI - High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up. AB - The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent (192)Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent >= 6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow up was 61 months (range, 25-94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach. PMID- 24222313 TI - Inferring functional interaction and transition patterns via dynamic Bayesian variable partition models. AB - Multivariate connectivity and functional dynamics have been of wide interest in the neuroimaging field, and a variety of methods have been developed to study functional interactions and dynamics. In contrast, the temporal dynamic transitions of multivariate functional interactions among brain networks, in particular, in resting state, have been much less explored. This article presents a novel dynamic Bayesian variable partition model (DBVPM) that simultaneously considers and models multivariate functional interactions and their dynamics via a unified Bayesian framework. The basic idea is to detect the temporal boundaries of piecewise quasi-stable functional interaction patterns, which are then modeled by representative signature patterns and whose temporal transitions are characterized by finite-state transition machines. Results on both simulated and experimental datasets demonstrated the effectiveness and accuracy of the DBVPM in dividing temporally transiting functional interaction patterns. The application of DBVPM on a post-traumatic stress disorder (PTSD) dataset revealed substantially different multivariate functional interaction signatures and temporal transitions in the default mode and emotion networks of PTSD patients, in comparison with those in healthy controls. This result demonstrated the utility of DBVPM in elucidating salient features that cannot be revealed by static pair-wise functional connectivity analysis. PMID- 24222314 TI - Signaling while eating: MCL is coupled with Mincle. AB - Recently, C-type lectin receptors (CLRs) have been identified as a newly emerging family of pattern-recognition receptors for pathogen-associated molecular patterns. The ligand and function of many "individual" CLRs have been clarified in the past few years. A new report by Lobato-Pascual et al. in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 3167-3174] shows that a rat CLR, named macrophage C-type lectin (also called Clec4d), forms a heterodimer with another CLR, macrophage inducible C-type lectin (also called Clec4e). This finding sheds light on a possible synergistic regulation of different C-type lectin receptors by forming heterodimers: such heterodimers may amplify signaling, expand ligand specificity, or confer multiple functions. PMID- 24222316 TI - 1,1-carbozirconation: unusual reaction of an alkyne with a methyl zirconocene cation and subsequent frustrated lewis pair like reactivity. AB - Boron chemistry without the boron: In a reaction analogous to 1,1-carboboration, [Cp*2 Zr?CH3 ](+) reacts with diphenylphosphino(trimethylsilyl)acetylene by 1,1 carbozirconation to give a vicinal [Zr](+) /P system. Like B/P frustrated Lewis pairs, the [Zr](+) /P system undergoes 1,2-addition to unsaturated compounds (including CO2 ) and reaction with metal complexes and up to three equivalents of CO. PMID- 24222315 TI - Treatment of dementia with lewy bodies. AB - OPINION STATEMENT: Dementia with Lewy bodies (DLB) is a multisystem disorder with diverse disease expression. A treatment regime restricted to the cognitive aspects of the disease does no favor to patients. Instead, patients should be educated to recognize the symptoms of this multisystem involvement. There are no treatments that slow the progression of disease, but symptomatic treatments can be effective. When thinking about treatment, we find it useful to divide the symptoms and signs into five categories: (a) cognitive features, (b) neuropsychiatric features, (c) motor dysfunction, (d) autonomic dysfunction, and (e) sleep dysfunction. Clinicians, funding bodies and industry are increasingly recognizing the importance of this common and debilitating disease. PMID- 24222317 TI - Tetrasomy 13q32.2qter due to an apparent inverted duplicated neocentric marker chromosome in an infant with hemangiomas, failure to thrive, laryngomalacia, and tethered cord. AB - BACKGROUND: Approximately 100 small supernumerary marker chromosomes (sSMCs) with a non-alpha-satellite neocentromere structure have been reported in the literature. Of the few derived from chromosome 13, five have consisted of inverted duplicated segment 13q32qter. CASE REPORT: We herein describe the sixth case, characterized by genome wide SNP array, conventional cytogenetics and FISH studies. The de novo occurrence of the marker, the poor prognosis and the presence of hemangiomas are consistent with previous cases. CONCLUSION: We hereby expand the clinical spectrum of this rare cytogenetic disorder and suggest a possible mechanism for the pathogenesis of associated congenital vascular malformations. PMID- 24222318 TI - The relational integration task explains fluid reasoning above and beyond other working memory tasks. AB - This study aimed to evaluate how well fluid reasoning can be predicted by a task that involves the monitoring of patterns of stimuli. This task is believed to measure the effectiveness of relational integration-the process that binds mental representations into more complex relational structures. In Experiments 1 and 2, the task was indeed validated as a proper measure of relational integration, since participants' performance depended on the number of bindings that had to be constructed in the diverse conditions of the task, whereas neither the number of objects to be bound nor the amount of elicited interference could affect this performance. In Experiment 3, by means of structural equation modeling and variance partitioning, the relation integration task was found to be the strongest predictor of fluid reasoning, explaining variance above and beyond the amounts accounted for by four other kinds of well-established working memory tasks. PMID- 24222319 TI - Odor-context effects in free recall after a short retention interval: a new methodology for controlling adaptation. AB - The present study investigated context effects of incidental odors in free recall after a short retention interval (5 min). With a short retention interval, the results are not confounded by extraneous odors or encounters with the experimental odor and possible rehearsal during a long retention interval. A short study time condition (4 s per item), predicted not to be affected by adaptation to the odor, and a long study time condition (8 s per item) were used. Additionally, we introduced a new method for recovery from adaptation, where a dissimilar odor was briefly presented at the beginning of the retention interval, and we demonstrated the effectiveness of this technique. An incidental learning paradigm was used to prevent overshadowing from confounding the results. In three experiments, undergraduates (N = 200) incidentally studied words presented one-by one and received a free recall test. Two pairs of odors and a third odor having different semantic-differential characteristics were selected from 14 familiar odors. One of the odors was presented during encoding, and during the test, the same odor (same-context condition) or the other odor within the pair (different context condition) was presented. Without using a recovery-from-adaptation method, a significant odor-context effect appeared in the 4-s/item condition, but not in the 8-s/item condition. Using the recovery-from-adaptation method, context effects were found for both the 8- and the 4-s/item conditions. The size of the recovered odor-context effect did not change with study time. There were no serial position effects. Implications of the present findings are discussed. PMID- 24222320 TI - Major hepatectomy is a safe modality for the treatment of intrahepatic cholangiocarcinoma in selected patients complicated with cirrhosis. AB - OBJECTIVE: The objective of this paper is to evaluate the perioperative outcomes of major hepatectomy for intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis. METHODS: We retrospectively evaluated the preoperative, intraoperative, and postoperative findings in 42 consecutive patients with cirrhosis and in 102 patients with normal livers who underwent major hepatectomy for ICC. RESULTS: Preoperative liver function was worse in patients with cirrhosis compared to patients without cirrhosis. Cirrhotic patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than non-cirrhotic patients. However, the two groups had similar overall morbidity and hospital mortality rates and similar rates of liver failure or other complications. Their R0 resection rates, resection margin widths and disease-free survival rates were also similar. CONCLUSIONS: Major hepatectomy for ICC can be performed in selected cirrhotic patients with acceptable morbidity and mortality rates, as compared to patients without cirrhosis. PMID- 24222322 TI - Retraction note: colorectal infraperitoneal anastomosis: the effects of perioperative supplemental oxygen administration on the anastomotic dehiscence. PMID- 24222321 TI - Does resident experience affect outcomes in complex abdominal surgery? Pancreaticoduodenectomy as an example. AB - OBJECTIVES: Understanding the factors contributing to improved postoperative patient outcomes remains paramount. For complex abdominal operations such as pancreaticoduodenectomy (PD), the influence of provider and hospital volume on surgical outcomes has been described. The impact of resident experience is less well understood. METHODS: We reviewed perioperative outcomes after PD at a single high-volume center between 2006 and 2012. Resident participation and outcomes were collected in a prospectively maintained database. Resident experience was defined as postgraduate year (PGY) and number of PDs performed. RESULTS: Forty three residents and four attending surgeons completed 686 PDs. The overall complication rate was 44 %; PD-specific complications (defined as pancreatic fistula, delayed gastric emptying, intraabdominal abscess, wound infection, and bile leak) occurred in 28 % of patients. The overall complication rates were similar when comparing PGY 4 to PGY 5 residents (55.3 vs. 43.0 %; p > 0.05). On univariate analysis, there was a difference in PD-specific complications seen between a PGY 4 as compared to a PGY 5 resident (44 vs. 27 %, respectively; p = 0.016). However, this was not statistically significant when adjusted for attending surgeon. Logistic regression demonstrated that as residents perform more cases, PD-specific complications decrease (OR = 0.97; p < 0.01). For a resident's first PD case, the predicted probability of a PD-specific complication is 27 %; this rate decreases to 19 % by resident case number 15. CONCLUSIONS: Complex cases, such as PD, provide unparalleled learning opportunities and remain an important component of surgical training. We highlight the impact of resident involvement in complex abdominal operations, demonstrating for the first time that as residents build experience with PD, patient outcomes improve. This is consistent with volume-outcome relationships for attending physicians and high volume hospitals. Maximizing resident repetitive exposure to complex procedures benefits both the patient and the trainee. PMID- 24222323 TI - A comparative study of 'fast-track' versus traditional peri-operative care protocols in gastrointestinal surgeries. AB - INTRODUCTION: A 'fast-track protocol' in surgery suggests the application of evidence-based practices to expedite patient recovery. It has shown to reduce hospital stay, hasten recovery as well as facilitate earlier return to work. It has a considerable impact in reducing healthcare costs. The basic tenet is to treat the patient's disease by minimal disturbance of their physiology. The protocol encompasses pre-operative, intra-operative and post-operative interventions which when carried out together would show maximal benefits. The surgeon is usually the leader of the team managing the patient, but it cannot be over-emphasised that this is a multi-disciplinary team approach. MATERIALS AND METHODS: We conducted a prospective interventional study to investigate whether 'fast-track' surgery protocols improve patient outcome when compared to traditional peri-operative care followed at our institute. By doing so, we observed that the patients who underwent 'fast tracking' required lesser analgesia, had earlier ambulation, earlier return of intestinal motility, were free from tubes, catheters and drains earlier and lastly were discharged earlier. This was achieved without a rise in complications or re-admissions. RESULTS/CONCLUSION: The results have proved that implementing the fast-track protocol for gastrointestinal surgeries is not only safe and effective, but also improves patient outcome. PMID- 24222324 TI - A new operative approach for type I choledochal cysts. AB - To present a novel modification of the surgical technique for open excision of type I choledochal cysts. The treatment of choice for choledochal cyst is surgical excision because such cysts are associated with an increased incidence of cancer. The commonly used operative technique provides poor access to the structures posterior to the cyst, principally the portal vein, and poor visibility of the junction of the cyst with the hepatic ducts and the pancreatic duct. The modification reduces these problems. The key operative step involves early transection of the choledochal cyst near its midpoint. This provides improved access to the back of the cyst. Slitting the sides of the cyst allows clear visibility from within the cyst of the union of the hepatic ducts with the cyst, and the entrance of the pancreatic duct, thus protecting them. Excision of type I choledochal cysts using the described method was completed in 11 adult patients between 2003 and 2012. One patient (9%) was found to have a concurrent gallbladder cancer and underwent an R0 resection at the time of choledochal cyst excision. No patients experienced any intraoperative complications. One patient (9%) developed a portal vein thrombosis postoperatively. The described technique is a safe and feasible method for the excision of extrahepatic choledochal cysts, and provides an advantage in allowing the surgeon to visualize the hepatic and pancreatic ducts from within the cyst and thus protect them during cyst excision. PMID- 24222325 TI - Intranodal lymphangiogenesis precedes development of lymph node metastasis and accelerates progression of gastric cancer. AB - INTRODUCTION: Peritumoral lymphangiogenesis is significantly correlated with lymph node metastasis and poor prognosis in various cancers. However, there are few reports concerning the role of intranodal lymphangiogenesis in lymphatic metastasis. The aim of this study was to examine the association of lymphangiogenesis in regional lymph nodes with the progression of gastric cancer. MATERIALS AND METHODS: Lymphatic vessel density (LVD) was immunohistochemically estimated in 1,596 lymph nodes from 52 patients who underwent gastrectomy. RESULTS: Intranodal LVD was significantly correlated with the size of metastasis and the progression of cancer. Patients in the high LVD group had significantly poorer prognosis relative to patients in the low LVD group. Furthermore, expression of VEGF-C mRNA was significantly up-regulated in lymph nodes of pathological node positive patients compared to node negative patients. DISCUSSION: Thus, intranodal lymphangiogenesis was correlated with nodal metastasis and poor prognosis of patients with gastric cancer. Lymphangiogenesis in regional lymph nodes plays an early role in spreading of tumor cells through the lymphatic system to distant organs in gastric cancer. PMID- 24222327 TI - Tehranolide inhibits cell proliferation via calmodulin inhibition, PDE, and PKA activation. AB - Tehranolide, natural sesquiterpene lactone with an endoperoxide group, has been shown to inhibit cell growth in cancer cells. Tehranolide was purified from Artemisia diffusa. To detect cell viability and proliferation, MTT assay was performed. In order to determine the role of tehranolide on calmodulin (CaM) structure and activity, its effects were evaluated with fluorescence emission spectra and CaM-mediated activation of phosphodiesterase (PDE1), in comparison with artemisinin. In fact, PDE1 inhibition, cAMP accumulation, and cAMP-dependent protein kinase A (PKA) activation were examined. The inhibitory effect of tehranolide on CaM structure is more than artemisinin. The kinetic analysis of tehranolide-CaM interaction has shown that this agent competitively inhibited the activation of PDE1 without affecting Vmax. Tehranolide increased Km value in higher amounts compared with artemisinin. Moreover, tehranolide had a cytotoxic effect on K562 cell line but not on normal human lymphocytes. Additionally, PDE inhibition and consequent cAMP accumulation and PKA activity were required for inhibiting cancer cell growth by tehranolide. Our results show that tehranolide significantly reduces cell proliferation in a time and dose-dependent manner in K562 cells via CaM inhibition, following PDE inhibition, cAMP accumulation, and consequent PKA activity. PMID- 24222328 TI - Induction of apoptosis by total flavonoids from Scutellaria barbata D. Don in human hepatocarcinoma MHCC97-H cells via the mitochondrial pathway. AB - Scutellaria barbata D. Don, a traditional Chinese medicine, reportedly possesses antitumor activity against a variety of tumors. In the present study, we investigated the cytotoxic effect of total flavonoids from S. barbata (TF-SB) on human hepatocarcinoma cells and the underlying molecular mechanisms regarding the effect were explored. TF-SB treatment significantly reduced the cell viability of human HCC MHCC97-H cells in a dose-dependent manner. Further flow cytometric analysis showed that the apoptosis rate of MHCC97-H cells increased and the mitochondrial membrane potential (?psim) of MHCC97-H cells decreased after TF-SB treatment. DNA ladder showed that TF-SB induced a significant increase in DNA fragmentation in MHCC97-H cells. Reverse transcription PCR and Western blot analysis revealed that the expression levels of Smac, Apaf-1, Cytochrome c, Caspase-9, and Caspase-3 were upregulated in a dose-dependent manner and after treatment with different concentrations of TF-SB for 48 h. These results suggest that TF-SB induces apoptosis in MHCC97-H cells through the mitochondrial pathway. PMID- 24222329 TI - A novel discriminant score based on tumor-associated trypsin inhibitor for accurate diagnosis of metastasis in patients with breast cancer. AB - Invasion and metastasis of solid tumors require proteolytic enzymes for degradation of the basal membrane and extracellular matrix. Currently, there are no reliable methodologies to predict the risk for metastatic disease. In this context, our aim has been focused on the development of a noninvasive score based on tumor-associated trypsin inhibitor (TATI) for the assessment of metastasis in patients with breast cancer. TATI, trypsin, and soluble epidermal growth factor receptor (sEGFR) were assayed by enzyme-linked immunosorbent assay. CA 15.3 serum level was assayed by microparticle enzyme immunoassay in 265 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver operating characteristic analysis curves. Using multivariate discriminant analysis, a score is selected based on absolute values of the four biochemical markers: TATI-metastatic breast cancer score (TATI-MBCS) = [0.03 * CA 15.3 (U/L) + 0.039 * TATI (ng/ml) + 0.04 * trypsin (ng/ml) + 0.023 * sEGFR (ng/ml) - 6.49 (numerical constant)]. This function correctly classified 84% of metastatic breast cancer at cutoff value = 0.62 (i.e., greater than 0.62 indicates patients with metastatic breast cancer and less than 0.62 indicates patients with nonmetastatic breast cancer). In conclusion, TATI-MBCS is a novel, noninvasive, and simple score which can be applied to discriminate patients with metastatic breast cancer. PMID- 24222330 TI - Neuroanastomosis and the innervation territory of the mental nerve. AB - The aim of this study was to clarify the distribution pattern and innervation territory of the mental nerve (MN) in the skin and mucosa by topographic examination by Sihler's staining, thereby providing reference anatomical information for surgical procedures and to enable prediction of regions of sensory disturbance following nerve damage. Ten human specimens were subjected to Sihler's staining, which is a highly accurate method for visualizing the distribution of nerve fibers without altering their topography. Each branch of the MN overlapped adjacent branches (five cases), or else they were distributed individually at the lower lip (five cases). The MN anastomosed with some branches of the facial nerve near the mental foramen. Moreover, some branches of the MN anastomosed with the buccal nerve of the trigeminal nerve, which supplies sensation to the skin and mucosa over the lateral region of the lower lip (six cases). The details of the distribution pattern and innervations territory of the MN presented herein may enable the prediction of a region of sensory disturbance following MN damage. Moreover, knowledge of the pattern of synapses with adjacent branches of other nerves, such as the facial (marginal mandibular and cervical branches) and the buccal nerves, might help to improve our understanding around incomplete anesthesia during the surgical procedures in oral & maxillofacial region. PMID- 24222331 TI - Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden. AB - In 728 Swedish cases of monoclonal gammopathy of undetermined significance (MGUS), followed up to 30 years (median, 10 years), we estimated the cumulative risk of hematologic disorders originating from lymphoid and myeloid lineages. Using Cox regression models, we examined associations of demographic and laboratory factors with progression and determined the discriminatory power of 3 prediction models for progression. Eighty-four MGUS cases developed a lymphoid disorder, representing a cumulative risk of 15.4%. Multiple myeloma (MM) occurred in 53 patients, and the 30-year cumulative risk was 10.6%; an ~0.5% annual risk. Three factors were significantly associated with progression: abnormal free light chain (FLC) ratio (<0.26 or >1.65), M-protein concentration (>=1.5 g/dL), and reduction of 1 or 2 noninvolved immunoglobulin isotype levels (immunoparesis). A prediction model with separate effects for these 3 factors and the M-protein isotype had higher discriminatory power than other models, although the differences were not statistically significant. The 30-year cumulative risk for myeloid malignancies was <2%. Our study confirms that abnormal FLC ratio and M protein concentration >1.5 g/dL, factors previously considered by Mayo Clinic researchers, are predictors for MM progression and suggests that separate consideration of immunoparesis and the Mayo Clinic risk factors could improve identification of MGUS patients at high risk for progression. PMID- 24222332 TI - Fetal hemoglobin in sickle cell anemia: a glass half full? AB - Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ~10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease. PMID- 24222334 TI - Fetal and umbilical Doppler ultrasound in high-risk pregnancies. AB - BACKGROUND: Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible false positive Doppler ultrasound findings could encourage inappropriate early delivery. OBJECTIVES: The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. SEARCH METHODS: We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 30 September 2013. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. MAIN RESULTS: Eighteen completed studies involving just over 10,000 women were included. The trials were generally of unclear quality with some evidence of possible publication bias. The use of Doppler ultrasound in high-risk pregnancy was associated with a reduction in perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352). There were also fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies). AUTHORS' CONCLUSIONS: Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less obstetric interventions. The quality of the current evidence was not of high quality, therefore, the results should be interpreted with some caution. Studies of high quality with follow-up studies on neurological development are needed. PMID- 24222333 TI - Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. AB - Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- <1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 * 10(9)/L (HR = 0.60, P = .005), and ETV6 RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups. PMID- 24222336 TI - Human dendritic cells - stars in the skin. AB - "A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells (DCs) are required to explain how this remarkable system is energized and directed." This is a quote by one of the greatest immunologists our community has ever known, and the father of dendritic cells, Ralph Steinman. Steinman's discovery of DCs in 1973 and his subsequent research opened a new field of study within immunology: DC biology and in particular the role of DCs in immune regulation in health and disease. Here, I review themes from our work and others on the complex network of dendritic cells in the skin and discuss the significance of skin DCs in understanding aspects of host defense against infections, the pathology of inflammatory skin diseases, and speculate on the future effective immune-based therapies. PMID- 24222335 TI - Quantitative structure-property relationship modeling of Gratzel solar cell dyes. AB - With fossil fuel reserves on the decline, there is increasing focus on the design and development of low-cost organic photovoltaic devices, in particular, dye sensitized solar cells (DSSCs). The power conversion efficiency (PCE) of a DSSC is heavily influenced by the chemical structure of the dye. However, as far as we know, no predictive quantitative structure-property relationship models for DSSCs with PCE as one of the response variables have been reported. Thus, we report for the first time the successful application of comparative molecular field analysis (CoMFA) and vibrational frequency-based eigenvalue (EVA) descriptors to model molecular structure-photovoltaic performance relationships for a set of 40 coumarin derivatives. The results show that the models obtained provide statistically robust predictions of important photovoltaic parameters such as PCE, the open-circuit voltage (V(OC)), short-circuit current (J(SC)) and the peak absorption wavelength lambda(max). Some of our findings based on the analysis of the models are in accordance with those reported in the literature. These structure-property relationships can be applied to the rational structural design and evaluation of new photovoltaic materials. PMID- 24222337 TI - Altered topological properties of the cortical motor-related network in patients with subcortical stroke revealed by graph theoretical analysis. AB - Cerebral neuroplasticity after stroke has been elucidated by functional neuroimaging. However, little is known concerning how topological properties of the cortical motor-related network evolved following subcortical stroke. In the present study, we investigated 24 subcortical stroke patients with only left motor pathway damaged and 24 matched healthy controls. A cortical motor-related network consisting of 20 brain regions remote from the primary lesion was constructed using resting-state functional MRI datasets. We subsequently used graph theoretical approaches to analyze the topological properties of this network in both stroke patients and healthy controls. In addition, we divided the stroke patients into two subgroups according to their outcomes in hand function to explore relationships between topological properties of this network and outcomes in hand function. Although we observed that the cortical motor-related network in both healthy controls and stroke patients exhibited small-world topology, the local efficiency of this network in stroke patients is higher than and global efficiency is lower than those in healthy controls. In addition, striking alterations in the betweenness centrality of regions were found in stroke patients, including the contralesional supplementary motor area, dorsolateral premotor cortex, and anterior inferior cerebellum. Moreover, we observed significant correlations between betweenness centrality of regions and Fugl-Meyer assessment scores. A tendency for the cortical motor-related network to be close to a regular configuration and altered betweenness centrality of regions were demonstrated in patients with subcortical stroke. This study provided insight into functional organization after subcortical stroke from the viewpoint of network topology. PMID- 24222339 TI - The evolution of premature reproductive senescence and menopause in human females : An evaluation of the "grandmother hypothesis". AB - Reproductive senescence in human females takes place long before other body functions senesce. This fact presents an evolutionary dilemma since continued reproduction should generally be favored by natural selection. Two commonly proposed hypotheses to account for human menopause are (a) a recent increase in the human lifespan and (b) a switch to investment in close kin rather than direct reproduction. No support is found for the proposition that human lifespans have only recently increased. Data from Ache hunter-gatherers are used to test the kin selection hypothesis. Ache data do not support the proposition that females can gain greater fitness benefits in old age by helping kin rather than continuing to reproduce. Nevertheless, one crucial parameter in the model, when adjusted to the highest value within the measured 95% confidence interval, would lead to the evolution of reproductive senescence at about 53 years of age. Further investigation is necessary to determine whether the kin selection hypothesis of menopause can account for its current maintenance in most populations. PMID- 24222338 TI - Menstrual synchrony : An update and review. AB - Several studies have now documented menstrual synchrony in human females. There is a broad consensus that the phenomenon mainly occurs in women who spend a significant amount of time together, such as close friends and coworkers, and that social contact rather than a similar environment plays an important role in mediating the effect. However, the mechanisms involved and the adaptive function of menstrual synchrony are not understood. There is some evidence that olfactory cues between females might underlie the effect. More research is needed before the precise mechanisms that regulate menstrual synchrony are elucidated. PMID- 24222340 TI - An evolutionary perspective on the patterning of maternal investment in pregnancy. AB - Pregnancy is thought to be a metabolically very expensive endeavor, yet investigations have produced inconsistent results concerning the responsiveness of human birth weight to maternal nutritional stress or nutritional intervention. These findings have led some researchers to conclude that fetal growth is strongly buffered against fluctuations in maternal energy balance, making the fetus in effect a "nearly perfect parasite." This buffering would appear to be a reasonable adaptive response given the high risk of morbidity and mortality associated with low birth weight. However, a life-history approach leads to the prediction that maternal investment strategies in pregnancy should be geared toward maximizing lifetime reproductive success rather than simply the success of the current pregnancy, and by extension that maternal investment strategies should vary with reproductive value. The physiology of human pregnancy in fact appears to include a number of mechanisms that protect maternal energy resources from diversion to the fetus and preserve them for future reproductive events. These mechanisms include adjustment of blood flow to the uterus and perhaps minor adjustments in gestation length, although evidence for the latter is scant. Suggestions are made for ways of investigating these maternal options. PMID- 24222341 TI - Preferential parental investment in daughters over sons. AB - Female-biased parental investment is unusual but not unknown in human societies. Relevant explanatory models include Fisher's principle, the Trivers-Willard model, local mate and resource competition and enhancement, and economic rational actor models. Possible evidence of female-biased parental investment includes sex ratios, mortality rates, parents' stated preferences for offspring of one sex, and direct and indirect measurements of actual parental behavior. Possible examples of female-biased parental investment include the Mukogodo of Kenya, the Ifalukese of Micronesia, the Cheyenne of North America, the Herero of southern Africa, the Kanjar of south Asia, the Mundugumor of New Guinea, contemporary North America, and historical Germany, Portugal, and the United States. PMID- 24222342 TI - A reply to Gelles: Stepchildrenare disproportionately abused, and diverse forms of violencecan share causal factors. PMID- 24222343 TI - A novel airway device with tactile sensing capabilities for verifying correct endotracheal tube placement. AB - We present a new device for verifying endotracheal tube (ETT) position that uses specialized sensors intended to distinguish anatomical features of the trachea and esophagus. This device has the potential to increase the safety of resuscitation, surgery, and mechanical ventilation and decrease the morbidity, mortality, and health care costs associated with esophageal intubation and unintended extubation by potentially improving the process and maintenance of endotracheal intubation. The device consists of a tactile sensor connected to the airway occlusion cuff of an ETT. It is intended to detect the presence or absence of tracheal rings immediately upon inflation of the airway occlusion cuff. The initial study detailed here verifies that a prototype device can detect contours similar to tracheal rings in a tracheal model. PMID- 24222344 TI - FaceTime((r)) for teaching ultrasound-guided anesthetic procedures in remote place. AB - In isolated area in Japan, only one anesthesiologist must often do new anesthetic techniques such as ultrasound-guided procedures without receiving any teaching. One solution to this problem may involve teleanesthesia, by which experienced anesthesiologists teach novices in remote places, by utilizing information communication technologies. FaceTimeTM (Apple, USA), which provides 120p of the resolution and 30 frames per second (fps) is an application of free visual communications using iPod TouchTM, iPhoneTM or iPadTM (Apple, USA). We investigated the delay time, the loss of the frames and the picture quality of iPad (as the device in the teaching site) in combination with iPod Touch, iPhone4 or iPhone5 (as the device in the isolated site) during FaceTime. At the operating rooms in Sado General Hospital (SGH) located in Sado Island (population; approximately 60,000), Japan, an anesthesiologist prepared 3 mobile devices (iPod Touch, iPhone4 or iPhone5). He called the other anesthesiologist at Yokohama City University Hospital (YCUH; approximately 300 km apart) by FaceTime using 1 of 3 mobile devices. The anesthesiologist at YCUH received the FaceTime call using iPad. After the connection was established, the display of the same cervical ultrasound image at SGH was sent to YCUH to evaluate the distinctness visually. Then we measured the delay time of every second (n = 60) and the loss of the frames (total frames = 30 fps * 60 s = 1,800) in each device for a minute. P < 0.01 was statistically significant. The quality of the pictures on the iPad display sent from iPhone5 was distinctly the best visually. The delay time of iPhone5 was significantly longer than the others (iPod Touch; 0.14 +/- 0.02 s, iPhone4; 0.13 +/- 0.02 s, iPhone5; 0.19 +/- 0.03 s), but clinically acceptable. The loss of the frames of iPhone5 (20; 1.1%) was significantly less than the others (iPhone4; 900, 50.0%, iPod Touch; 902, 50.1%). To teach anesthetic techniques in remote place by FaceTime, iPhone5 as the devise in isolate site was optimum compared with iPod Touch and iPhone4. PMID- 24222345 TI - Interactions among glucose delivery, transport, and phosphorylation that underlie skeletal muscle insulin resistance in obesity and type 2 Diabetes: studies with dynamic PET imaging. AB - Dynamic positron emission tomography (PET) imaging was performed using sequential tracer injections ([(15)O]H2O, [(11)C]3-O-methylglucose [3-OMG], and [(18)F]fluorodeoxyglucose [FDG]) to quantify, respectively, skeletal muscle tissue perfusion (glucose delivery), kinetics of bidirectional glucose transport, and glucose phosphorylation to interrogate the individual contribution and interaction among these steps in muscle insulin resistance (IR) in type 2 diabetes (T2D). PET imaging was performed in normal weight nondiabetic subjects (NW) (n = 5), obese nondiabetic subjects (OB) (n = 6), and obese subjects with T2D (n = 7) during fasting conditions and separately during a 6-h euglycemic insulin infusion at 40 mU . m(-2) . min(-1). Tissue tracer activities were derived specifically within the soleus muscle with PET images and magnetic resonance imaging. During fasting, NW, OB, and T2D subjects had similar [(11)C]3 OMG and [(18)F]FDG uptake despite group differences for tissue perfusion. During insulin-stimulated conditions, IR was clearly evident in T2D (P < 0.01), and [(18)F]FDG uptake by muscle was inversely correlated with systemic IR (P < 0.001). The increase in insulin-stimulated glucose transport was less (P < 0.01) in T2D (twofold) than in NW (sevenfold) or OB (sixfold) subjects. The fractional phosphorylation of [(18)F]FDG during insulin infusion was also significantly lower in T2D (P < 0.01). Dynamic triple-tracer PET imaging indicates that skeletal muscle IR in T2D involves a severe impairment of glucose transport and additional impairment in the efficiency of glucose phosphorylation. PMID- 24222346 TI - The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes. AB - Reduced expression of the INDY (I'm not dead yet) tricarboxylate carrier increased the life span in different species by mechanisms akin to caloric restriction. Mammalian INDY homolog (mIndy, SLC13A5) gene expression seems to be regulated by hormonal and/or nutritional factors. The underlying mechanisms are still unknown. The current study revealed that mIndy expression and [(14)C] citrate uptake was induced by physiological concentrations of glucagon via a cAMP dependent and cAMP-responsive element-binding protein (CREB)-dependent mechanism in primary rat hepatocytes. The promoter sequence of mIndy located upstream of the most frequent transcription start site was determined by 5'-rapid amplification of cDNA ends. In silico analysis identified a CREB-binding site within this promoter fragment of mIndy. Functional relevance for the CREB-binding site was demonstrated with reporter gene constructs that were induced by CREB activation when under the control of a fragment of a wild-type promoter, whereas promoter activity was lost after site-directed mutagenesis of the CREB-binding site. Moreover, CREB binding to this promoter element was confirmed by chromatin immunoprecipitation in rat liver. In vivo studies revealed that mIndy was induced in livers of fasted as well as in high-fat-diet-streptozotocin diabetic rats, in which CREB is constitutively activated. mIndy induction was completely prevented when CREB was depleted in these rats by antisense oligonucleotides. Together, these data suggest that mIndy is a CREB-dependent glucagon target gene that is induced in fasting and in type 2 diabetes. Increased mIndy expression might contribute to the metabolic consequences of diabetes in the liver. PMID- 24222347 TI - Role of synaptic plasticity and EphA5-ephrinA5 interaction within the ventromedial hypothalamus in response to recurrent hypoglycemia. AB - Hypoglycemia stimulates counterregulatory hormone release to restore euglycemia. This protective response is diminished by recurrent hypoglycemia, limiting the benefits of intensive insulin treatment in patients with diabetes. We previously reported that EphA5 receptor-ephrinA5 interactions within the ventromedial hypothalamus (VMH) influence counterregulatory hormone responses during acute hypoglycemia in nondiabetic rats. In this study, we examined whether recurrent hypoglycemia alters the capacity of the ephrinA5 ligand to activate VMH EphA5 receptors, and if so, whether these changes could contribute to pathogenesis of defective glucose counterregulation in response to a standard hypoglycemic stimulus. The expression of ephrinA5, but not EphA5 receptors within the VMH, was reduced by antecedent recurrent hypoglycemia. In addition, the number of synaptic connections was increased and astroglial synaptic coverage was reduced. Activation of VMH EphA5 receptors via targeted microinjection of ephrinA5-Fc before a hyperinsulinemic hypoglycemic clamp study caused a reduction in the glucose infusion rate in nondiabetic rats exposed to recurrent hypoglycemia. The increase in the counterregulatory response to insulin-induced hypoglycemia was associated with a 150% increase in glucagon release (P < 0.001). These data suggest that changes in ephrinA5/EphA5 interactions and synaptic plasticity within the VMH, a key glucose-sensing region in the brain, may contribute to the impairment in glucagon secretion and counterregulatory responses caused by recurrent hypoglycemia. PMID- 24222348 TI - Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. AB - C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) are associated with cardiovascular disease (CVD) and death in general populations. However, studies of these factors in type 2 diabetes are limited. We studied their associations with the risk of major macrovascular events, microvascular complications, and mortality in patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. Plasma CRP, fibrinogen, and IL-6 levels were determined in a case-cohort study (n = 3,865) nested within the 11,140 men and women with type 2 diabetes and baseline CVD or risk factors in the ADVANCE Study. All three biomarkers of inflammation were associated with an increased risk of macrovascular events and death in analyses adjusted for age, sex, and treatment groups. After further adjustment, only IL-6 was an independent predictor of macrovascular events (hazard ratio per SD increase 1.37 [95% CI 1.24 1.51]) and death (1.35 [1.23-1.49]). IL-6 significantly improved the prediction of macrovascular events and death. After adjustment, none of the markers predicted microvascular complications. We conclude that IL-6 levels, but not CRP or fibrinogen levels, add significantly to the prediction of macrovascular events and mortality in individuals with type 2 diabetes who have baseline CVD or risk factors. PMID- 24222349 TI - Occurrence of spontaneous pancreatic lesions in normal and diabetic rats: a potential confounding factor in the nonclinical assessment of GLP-1-based therapies. AB - Glucagon-like peptide 1-based therapies, collectively described as incretins, produce glycemic benefits in the treatment of type 2 diabetes. Recent publications raised concern for a potential increased risk of pancreatitis and pancreatic cancer with incretins based in part on findings from a small number of rodents. However, extensive toxicology assessments in a substantial number of animals dosed up to 2 years at high multiples of human exposure do not support these concerns. We hypothesized that the lesions being attributed to incretins are commonly observed background findings and endeavored to characterize the incidence of spontaneous pancreatic lesions in three rat strains (Sprague-Dawley [S-D] rats, Zucker diabetic fatty [ZDF] rats, and rats expressing human islet amyloid polypeptide [HIP]; n = 36/group) on a normal or high-fat diet over 4 months. Pancreatic findings in all groups included focal exocrine degeneration, atrophy, inflammation, ductular cell proliferation, and/or observations in large pancreatic ducts similar to those described in the literature, with an incidence of exocrine atrophy/inflammation seen in S-D (42-72%), HIP (39%), and ZDF (6%) rats. These data indicate that the pancreatic findings attributed to incretins are common background findings, observed without drug treatment and independent of diet or glycemic status, suggesting a need to exercise caution when interpreting the relevance of some recent reports regarding human safety. PMID- 24222351 TI - Resident macrophages mediate islet amyloid polypeptide-induced islet IL-1beta production and beta-cell dysfunction. AB - Islet amyloid polypeptide (IAPP) aggregates to form amyloid fibrils in patients with type 2 diabetes and acts as a potent stimulus for interleukin (IL)-1beta secretion by bone marrow-derived macrophages. We sought to determine the contribution of resident islet macrophages to IAPP-induced inflammation and beta cell dysfunction. In cultured islets, macrophages (F4/80(+)CD11b(+)CD11c(+) cells) were required for IAPP-induced mRNA expression of the proinflammatory cytokines IL-1beta, tumor necrosis factor-alpha, and IL-6 and the anti inflammatory cytokines IL-10 and IL-1 receptor antagonist. Moreover, IAPP-induced IL-1beta synthesis and caspase-1 activation were detected in macrophages but not other islet cell types. Transgenic mice with beta-cell human IAPP (hIAPP) expression had impaired glucose tolerance, elevated islet Il1b mRNA, and decreased Il10 and Il1rn expression following high-fat feeding. Islet macrophages were the major source of these transcripts and expressed increased cell surface Ly6C and CD11c in hIAPP transgenic mice. Clodronate liposome-mediated depletion of islet macrophages improved glucose tolerance and blocked proinflammatory gene expression in hIAPP-expressing mice, despite increasing the amount of islet amyloid. These data provide the first evidence that IAPP aggregates skew resident islet macrophages toward a proinflammatory phenotype and suggest a mechanism by which anti-inflammatory therapies may protect beta-cells from IAPP-induced islet dysfunction. PMID- 24222352 TI - Coupling between transcription and alternative splicing. AB - The scenario of alternative splicing regulation is far more complex than the classical picture of a pre-mRNA being processed post-transcriptionally in more than one way. Introns are efficiently removed while transcripts are still being synthesized, supporting the idea of a co-transcriptional regulation of alternative splicing. Evidence of a functional coupling between splicing and transcription has recently emerged as it was observed that properties of one process may affect the outcome of the other. Co-transcriptionality is thought to improve splicing efficiency and kinetics by directing the nascent pre-mRNA into proper spliceosome assembly and favoring splicing factor recruitment. Two models have been proposed to explain the coupling of transcription and alternative splicing: in the recruitment model, promoters and pol II status affect the recruitment to the transcribing gene of splicing factors or bifunctional factors acting on both transcription and splicing; in the kinetic model, differences in the elongation rate of pol II would determine the timing in which splicing sites are presented, and thus the outcome of alternative splicing decisions. In the later model, chromatin structure has emerged as a key regulator. Although definitive evidence for transcriptionally coupled alternative splicing alterations in tumor development or cancer pathogenesis is still missing, many alternative splicing events altered in cancer might be subject to transcription splicing coupling regulation. PMID- 24222350 TI - T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance. AB - A key pathophysiologic role for activated T-cells in mediating adipose inflammation and insulin resistance (IR) has been recently postulated. However, mechanisms underlying their activation are poorly understood. In this study, we demonstrated a previously unrecognized homeostatic role for the costimulatory B7 molecules (CD80 and CD86) in preventing adipose inflammation. Instead of promoting inflammation, which was found in many other disease conditions, B7 costimulation reduced adipose inflammation by maintaining regulatory T-cell (Treg) numbers in adipose tissue. In both humans and mice, expression of CD80 and CD86 was negatively correlated with the degree of IR and adipose tissue macrophage infiltration. Decreased B7 expression in obesity appeared to directly impair Treg proliferation and function that lead to excessive proinflammatory macrophages and the development of IR. CD80/CD86 double knockout (B7 KO) mice had enhanced adipose macrophage inflammation and IR under both high-fat and normal diet conditions, accompanied by reduced Treg development and proliferation. Adoptive transfer of Tregs reversed IR and adipose inflammation in B7 KO mice. Our results suggest an essential role for B7 in maintaining Tregs and adipose homeostasis and may have important implications for therapies that target costimulation in type 2 diabetes. PMID- 24222353 TI - Detection of Alternatively Spliced or Processed RNAs in Cancer Using Oligonucleotide Microarray. AB - Deregulation of gene expression plays a pivotal role in tumorigenesis, so the ability to detect RNA alterations is of great value in cancer diagnosis and management. DNA microarrays have been used to measure changes in mRNA or microRNA level, but less often the change of RNA isoforms. Here we appraise the utilization of microarray in detecting alternatively processed RNAs, which have alternative splice forms, retained introns, or altered 3' untranslated regions. We cover the methodology and focus on cancer studies. Recent development in parallel or deep sequencing used in transcriptome analysis is also discussed. PMID- 24222354 TI - Cancer-Associated Perturbations in Alternative Pre-messenger RNA Splicing. AB - For most of our 25,000 genes, the removal of introns by pre-messenger RNA (pre mRNA) splicing represents an essential step toward the production of functional messenger RNAs (mRNAs). Alternative splicing of a single pre-mRNA results in the production of different mRNAs. Although complex organisms use alternative splicing to expand protein function and phenotypic diversity, patterns of alternative splicing are often altered in cancer cells. Alternative splicing contributes to tumorigenesis by producing splice isoforms that can stimulate cell proliferation and cell migration or induce resistance to apoptosis and anticancer agents. Cancer-specific changes in splicing profiles can occur through mutations that are affecting splice sites and splicing control elements, and also by alterations in the expression of proteins that control splicing decisions. Recent progress in global approaches that interrogate splicing diversity should help to obtain specific splicing signatures for cancer types. The development of innovative approaches for annotating and reprogramming splicing events will more fully establish the essential contribution of alternative splicing to the biology of cancer and will hopefully provide novel targets and anticancer strategies. Metazoan genes are usually made up of several exons interrupted by introns. The introns are removed from the pre-mRNA by RNA splicing. In conjunction with other maturation steps, such as capping and polyadenylation, the spliced mRNA is then transported to the cytoplasm to be translated into a functional protein. The basic mechanism of splicing requires accurate recognition of each extremity of each intron by the spliceosome. Introns are identified by the binding of U1 snRNP to the 5' splice site and the U2AF65/U2AF35 complex to the 3' splice site. Following these interactions, other proteins and snRNPs are recruited to generate the complete spliceosomal complex needed to excise the intron. While many introns are constitutively removed by the spliceosome, other splice junctions are not used systematically, generating the phenomenon of alternative splicing. Alternative splicing is therefore the process by which a single species of pre mRNA can be matured to produce different mRNA molecules (Fig. 1). Depending on the number and types of alternative splicing events, a pre-mRNA can generate from two to several thousands different mRNAs leading to the production of a corresponding number of proteins. It is now believed that the expression of at least 70 % of human genes is subjected to alternative splicing, implying an enormous contribution to proteomic diversity, and by extension, to the development and the evolution of complex animals. Defects in splicing have been associated with human diseases (Caceres and Kornblihtt, Trends Genet 18(4):186 93, 2002, Cartegni et al., Nat Rev Genet 3(4):285-98, 2002, Pagani and Baralle, Nat Rev Genet 5(5):389-96, 2004), including cancer (Brinkman, Clin Biochem 37(7):584-94, 2004, Venables, Bioessays 28(4):378-86, 2006, Srebrow and Kornblihtt, J Cell Sci 119(Pt 13):2635-2641, 2006, Revil et al., Bull Cancer 93(9):909-919, 2006, Venables, Transworld Res Network, 2006, Pajares et al., Lancet Oncol 8(4):349-57, 2007, Skotheim and Nees, Int J Biochem Cell Biol 39:1432-1449, 2007). Numerous studies have now confirmed the existence of specific differences in the alternative splicing profiles between normal and cancer tissues. Although there are a few cases where specific mutations are the primary cause for these changes, global alterations in alternative splicing in cancer cells may be primarily derived from changes in the expression of RNA binding proteins that control splice site selection. Overall, these cancer specific differences in alternative splicing offer an immense potential to improve the diagnosis and the prognosis of cancer. This review will focus on the functional impact of cancer-associated alternative splicing variants, the molecular determinants that alter the splicing decisions in cancer cells, and future therapeutic strategies. PMID- 24222355 TI - Alternative splicing of tumor suppressors and oncogenes. AB - Alternative splicing is a fundamental mechanism to modulate gene expression programs in response to different growth and environmental stimuli. There is now ample evidence that alternative splicing errors, caused by mutations in cis acting elements and defects and/or imbalances in trans-acting factors, may be causatively associated to cancer progression. Recent work indicates the existence of an intricate network of interactions between alternative splicing events and signal transduction pathways. In this network, splicing factors occupy a central position and appear to function both as targets and effectors of regulatory circuits. Thus, a change in their activity deeply affects alternative splicing profiles and hence the cell behavior. Here, we discuss a number of cases that exemplify the involvement of deregulated alternative splicing in tumor progression. PMID- 24222356 TI - MicroRNAs in Cancer. AB - MicroRNAs (miRNAs) are a group of endogenous, small noncoding RNAs of approximately 22 nucleotides in lengths. As a new class of signaling modulators, miRNAs have attracted great attention for their unique features, including multitarget regulation, tissue specificity, and evolutionary conservation. These small endogenous RNAs are able to interact with many important genes and play critical roles in a wide range of biological processes, including cell proliferation and differentiation. Strikingly, miRNAs are frequently dysregulated in human cancers. A number of studies have shown that miRNAs are involved in cancer pathogenesis by regulating oncogenes or tumor suppressor genes. Here, we review recent studies of miRNAs in cancer development and discuss their potential applications in cancer therapeutics. PMID- 24222358 TI - Regulation of ARE-mRNA Stability by Cellular Signaling: Implications for Human Cancer. AB - During recent years, it has become clear that regulation of mRNA stability is an important event in the control of gene expression. The stability of a large class of mammalian mRNAs is regulated by AU-rich elements (AREs) located in the mRNA 3' UTRs. mRNAs with AREs are inherently labile but as a response to different cellular cues they can become either stabilized, allowing expression of a given gene, or further destabilized to silence their expression. These tightly regulated mRNAs include many that encode growth factors, proto-oncogenes, cytokines, and cell cycle regulators. Failure to properly regulate their stability can therefore lead to uncontrolled expression of factors associated with cell proliferation and has been implicated in several human cancers. A number of transfactors that recognize AREs and regulate the translation and degradation of ARE-mRNAs have been identified. These transfactors are regulated by signal transduction pathways, which are often misregulated in cancers. This chapter focuses on the function of ARE-binding proteins with an emphasis on their regulation by signaling pathways and the implications for human cancer. PMID- 24222357 TI - The perinucleolar compartment: RNA metabolism and cancer. AB - The perinucleolar compartment (PNC) is a nuclear substructure associated with, but structurally distinct from, the nucleolus. The PNC contains several RNA processing proteins and several RNA pol III transcripts, which form novel complexes. As determined by cell culture experiments and human tumor samples, the PNC forms exclusively in cancer cells and the percentage of cancer cells in a population that have one or more PNCs directly correlates with the malignancy of that population of cells. Therefore, the PNC is being developed as a prognostic marker for several malignancies. PNC elimination in cancer cells has proven to be a useful as screening method to discover probe compounds used to elucidate PNC biology and to discover compounds with the potential to be developed as minimally toxic anti-cancer drugs. PMID- 24222359 TI - Alternative Pre-mRNA Splicing, Cell Death, and Cancer. AB - Alternative splicing is one of the most powerful mechanisms for generating functionally distinct products from a single genetic loci and for fine-tuning gene activities at the post-transcriptional level. Alternative splicing plays important roles in regulating genes critical for cell death. These cell death genes encode death ligands, cell surface death receptors, intracellular death regulators, signal transduction molecules, and death executor enzymes such as caspases and nucleases. Alternative splicing of these genes often leads to the formation of functionally different products, some of which have antagonistic effects that are either cell death-promoting or cell death-preventing. Differential alternative splicing can affect expression, subcellular distribution, and functional activities of the gene products. Molecular defects in splicing regulation of cell death genes have been associated with cancer development and resistance to treatment. Studies using molecular, biochemical, and systems-based approaches have begun to reveal mechanisms underlying the regulation of alternative splicing of cell death genes. Systematic studies have begun to uncover the multi-level interconnected networks that regulate alternative splicing. A global picture of the complex mechanisms that regulate cell death genes at the pre-mRNA splicing level has thus begun to emerge. PMID- 24222360 TI - Oligonucleotide therapeutics in cancer. AB - Alterations in pre-mRNA splicing can have profound effects on gene expression and lead to cellular transformation. Oligonucleotide therapeutics are drugs that manipulate gene expression and improve the disease state. Antisense oligonucleotides hybridize with a target mRNA to downregulate gene expression via an RNase H-dependent mechanism. Additionally, RNase H-independent splice switching oligonucleotides (SSO) modulate alternative or aberrant splicing, to favor the therapeutically relevant splicing product. This chapter summarizes the progress made in the application of these oligonucleotide drugs in the treatment of cancer. PMID- 24222361 TI - Clinical perspective on chemo-resistance and the role of RNA processing. AB - Pre-messenger RNA splicing is significantly changed in cancer cells leading to the expression of cancer-specific transcripts. These transcripts have the potential to be used as cancer biomarkers and also as targets for new therapeutic approaches. In addition, the cancer-specific transcripts have the potential to alter the drug response of the cancer cells creating a chemo-resistant state. This later property of alternative splicing presents a challenge to clinicians in the design of effective therapeutic regimens. When a patient's cancer relapses it is frequently refractory to standard chemotherapies resulting in a poor clinical outcome. Therefore, understanding the mechanisms of how alternative splicing can lead to chemo-resistance is critical to the effective delivery of treatment. Here, we will discuss the impact of alternative splicing variants on drug metabolism and activation; on drug interactions with cell signaling pathways; and on cell death pathways in cancer therapeutics. In addition to the initial characterization of splicing variants, the mechanisms leading to alterations in splicing are being studied in the setting of chemo-resistance and will be discussed here. The promise of therapeutic intervention to obviate the impact of these splicing variants will significantly enhance treatment options for cancer patients. PMID- 24222362 TI - Expanding the scope of biomass-derived chemicals through tandem reactions based on oxorhenium-catalyzed deoxydehydration. AB - New modes of DODH: Oxorhenium compounds act as deoxydehydration(DODH)/acid dual purpose catalysts to transform biomass-derived diol substrates into a variety of commodity chemical precursors. The power of this approach is highlighted by a tandem [1,3]-OH shift/DODH of 2-ene-1,4-diols and 2,4-diene-1,6-diols, and by a DODH/esterification sequence of sugar acids to unsaturated esters for the production of polymers and plasticizers. PMID- 24222363 TI - Capsule commentary on Ursua et al., awareness, treatment and control of hypertension among Filipino immigrants. PMID- 24222364 TI - Capsule commentary on Sentell et al., the influence of community and individual health literacy on self-reported health status. PMID- 24222365 TI - Outpatient versus inpatient induction of labour for improving birth outcomes. AB - BACKGROUND: More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. OBJECTIVES: To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013). SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. MAIN RESULTS: We included four trials, with a combined total of 1439 women in the review; each trial examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (two studies including 1028 women). There were no differences between women managed as outpatients versus inpatients for most review outcomes. There was no evidence of a difference between the likelihood of women requiring instrumental delivery in either setting (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.79 to 2.13). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10 mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale, RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. AUTHORS' CONCLUSIONS: The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings. PMID- 24222366 TI - Failure to replicate the Mehta and Zhu (2009) color-priming effect on anagram solution times. AB - Mehta and Zhu (Science, 323, 1226-1229, 2009) hypothesized that the color red induces avoidance motivation and that the color blue induces approach motivation. In one experiment, they reported that anagrams of avoidance motivation words were solved more quickly on red backgrounds and that approach motivation anagrams were solved more quickly on blue backgrounds. Reported here is a direct replication of that experiment, using the same anagrams, instructions, and colors, with more than triple the number of participants used in the original study. The results did not show the Mehta and Zhu color-priming effects, even though statistical power was sufficient to detect the effect. The results call into question the existence of their color-priming effect on the solution of anagrams. PMID- 24222367 TI - Grasping numbers: evidence for automatic influence of numerical magnitude on grip aperture. AB - Previous research has shown that the fingers' aperture during grasp is affected by the numerical values of numbers embedded in the grasped objects: Numerically larger digits lead to larger grip apertures than do numerically smaller digits during the initial stages of the grasp. The relationship between numerical magnitude and visuomotor control has been taken to support the idea of a common underlying neural system mediating the processing of magnitude and the computation of object size for motor control. The purpose of the present study was to test whether the effect of magnitude on motor preparation is automatic. During grasping, we asked participants to attend to the colors of the digit while ignoring numerical magnitude. The results showed that numerical magnitude affected grip aperture during the initial stages of the grasp, even when magnitude information was irrelevant to the task at hand. These findings suggest that magnitude affects grasping preparation in an automatic fashion. PMID- 24222368 TI - Primary extrahepatic portal vein obstruction in adults: a single center experience. AB - BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) is a heterogenous disease with regards to etiology, pathogenesis, age, and geographical location. This study analyzed our experience with EHPVO in adults aged >20 years. EHPVO associated with pancreatitis and abdominal lymph node tuberculosis compressing the portal vein was excluded. METHODS: Retrospective analysis of the hospital database from January 2000 to December 2009 was done. All patients with liver disease who are attending our department were also prospectively evaluated with Doppler ultrasound for the portal venous system to study the prevalence of EHPVO. Clinical, biochemical, and imaging findings; work up for thrombophilia; treatment given; and follow up were evaluated. RESULT: In the retrospective analysis, primary EHPVO in adults was seen in 108/10,095 (1 %), and in the prospective analysis, it was seen in 16/2,188 (0.73 %). The main clinical presentations were abdominal pain and variceal bleed. Imaging findings included portal cavernoma, portal biliopathy, gallbladder calculi, collaterals, and ascites. The major causative factors identified were hyperhomocysteinemia, antiphospholipid antibodies, and myeloproliferative disorders, while, in a third of patients, none of these risk factors could be identified. Twelve patients were subjected to surgery, while the remaining patients were managed either by medical, endoscopic, or interventional radiological techniques. More than 2 years of follow up was available in 90 patients; two patients died due to uncontrolled bleeding, seven patients required surgery, seven patients showed deterioration in liver function, and one patient developed hepatocellular carcinoma. In the prospective study, three patients were subjected to surgery, and the others were managed medically. CONCLUSION: Primary EHPVO is an uncommon cause of portal hypertension in adults in India, and its etiological spectrum is comparable to the West. PMID- 24222369 TI - Profile of hepatocellular carcinoma in a tertiary care hospital in Punjab in northern India. AB - PURPOSE/AIM: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in all parts of the world. We analyzed the clinical presentation, etiology, and tumor characteristics of HCC presenting to our hospital. METHODS: All patients diagnosed to have HCC from September 2007 to August 2010 were prospectively enrolled. HCC was diagnosed according to EASL criteria-USG/CT/MRI of the abdomen and/or serum alpha-fetoprotein and/or histology (where indicated). Detailed clinical and laboratory parameters were noted. Barcelona Clinic Liver Cancer (BCLC) staging was done. RESULTS: One hundred and twenty-eight patients (22 females, mean +/- SD; age, 49.8 +/- 10.2 years) were diagnosed to have HCC. Underlying cirrhosis was present in 99.2 %. Hepatitis C virus infection, alone (21.9 %) or with alcohol (22.9 %) was the most common etiological factor, followed by alcohol alone; 33.6 % of the patients had more than one etiological factor. Most patients (83.5 %) presented with features of decompensated cirrhosis. HCC leading to decompensation of cirrhosis was the first presentation of the liver disease in nearly one third of the cases. Serum alpha-fetoprotein was >200 ng/mL in 67.2 % of the patients, while it was normal in 18.7 % of the patients. The mean +/- SD size of HCC was 5.3 +/- 2.9 cm. HCC was multicentric in 57 %, and portal vein thrombosis was present in 34.4 %. About 66 % of the patients belonged to BCLC stage C or D. CONCLUSIONS: Hepatitis C virus infection was the most common cause of HCC in Punjab. One-third of the patients had multiple etiological factors and almost all had underlying cirrhosis and presented at advanced stage. PMID- 24222370 TI - Button battery ingestion in children--what one needs to know? PMID- 24222371 TI - Alagille syndrome: experience of a tertiary care center in North India. AB - Alagille syndrome (AGS) is an autosomal dominant disorder of chronic cholestasis characterized by paucity of interlobular bile ducts. The condition has been described only as isolated case reports in India. We describe clinical profile and outcome of nine subjects (six infants and three older children) with AGS. Cholestasis and characteristic facies were present in all, followed by congenital heart disease, vertebral anomalies, and posterior embryotoxon in seven, five, and four cases, respectively. Pruritus was the commonest symptom which was refractory to medical treatment in one third of cases. Two cases developed decompensated liver disease on follow up. High index of suspicion for this multisystemic condition is essential for correct diagnosis and management. PMID- 24222372 TI - Randomized clinical trial: atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. AB - BACKGROUND: Statins are known to possess pleiotropic anti-inflammatory properties which have been evaluated for clinical benefits in a number of disorders. Studies have demonstrated beneficial actions of statins in experimental models of colitis. Clinical evidence in acute exacerbation of ulcerative colitis (UC) is lacking. AIM: This study aims to assess the efficacy and safety of add-on atorvastatin in mild to moderately severe acute exacerbation of UC. METHODS: Patients with acute exacerbation of UC were randomized to receive either atorvastatin (20 mg) or matching placebo once daily orally for 8 weeks in addition to the standard therapy. Clinical efficacy was assessed by using partial Mayo score (PMS). RESULTS: Previously diagnosed 64 cases of UC presenting with mild to moderately severe acute exacerbation were randomized to receive either atorvastatin of 20 mg or placebo. Mean PMS increased by 1.5 points and decreased by 0.31 points in atorvastatin and placebo groups, respectively, at 8 weeks compared to the baseline values (p = 0.04). Eight (25 %) and 13 (40.6 %) patients attained the primary outcome criteria for clinical improvement in the atorvastatin and placebo arms, respectively (p = 0.18). Fifteen (46.8 %) patients in the atorvastatin group and no patient in the placebo group had >=2 point increase in PMS after 8 weeks (p < 0.001). CONCLUSION: Atorvastatin therapy in acute exacerbation of UC may not be associated with beneficial effects. Paradoxical increase in disease activity may be seen in some patients. However, these findings need to be substantiated in larger studies. PMID- 24222373 TI - Clinical profile of early-onset and late-onset idiopathic chronic pancreatitis in South India. AB - BACKGROUND AND AIM: Idiopathic chronic pancreatitis (ICP) is the most common form of chronic pancreatitis reported in India. There is paucity of literature on the prevalence and profiles of early- and late-onset forms of ICP in India. MATERIAL AND METHODS: We compared the profile of early- and late-onset ICP in a patient population attending a tertiary care hospital in South India. RESULTS: Pain was the characteristic feature as more than 90 % with both early-onset and late-onset ICP had pain as the most significant symptom. Onset of pain was at age 14.9 +/- 7.7 years in early-onset and at 38.1 +/- 9.9 in late-onset ICP (p < 0.001). There was considerable delay between onset of pain in early onset as compared to late onset ICP. Diabetes was seen in 41.4 % in early-onset as compared to 69.1 % in late-onset ICP (p < 0.001). Pancreatic exocrine insufficiency was seen in 34.4 % in early-onset as compared to 53.2 % in late-onset ICP (p < 0.001). Increased prevalence of exocrine insufficiency and diabetes was observed in late-onset as compared to early-onset ICP. Univariate analysis showed that alcohol use, smoking, age, and family history of diabetes were significantly associated with diabetes. Multivariate analysis showed strong associations for diabetes with smoking (odds ratio (OR) = 4.2), calcification (OR = 7.7), as well as family history and age >40 years. CONCLUSIONS: There were differences between early onset and late-onset ICP in southern Indian patients. Diabetes was strongly associated with smoking and pancreatic calcification. PMID- 24222375 TI - XIV ISCM, Hangzhou, China, May 2013: opening remarks. PMID- 24222374 TI - PrP106-126 and Abeta 1-42 peptides induce BV-2 microglia chemotaxis and proliferation. AB - Transmissible spongiform encephalopathies (TSEs) and Alzheimer's disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrP(Sc) and Abeta in TSEs and AD, respectively). To better understand how protein aggregates can modulate microglial processes in these diseases, we treated BV-2 microglia with PrP(106-126) or Abeta1-42 peptides individually at three different concentrations (25-100 MUM PrP(106-12) and 2.5-10 MUM Abeta1-42) or with a mixture of PrP(106-126) and Abeta1-42 peptides at specified concentrations for 6 24 h. BV-2 microglia chemotaxis, proliferation, and monocyte chemoattractant protein-1 and transforming growth factor-beta1 (TGF-beta1) secretion were measured and compared between treatments. The results demonstrate that PrP(106 126) and Abeta1-42 peptides induce increases in all four parameters from 6 to 12 h. However, the measured indices plateaued beyond 12 h in BV-2 cells treated >50 MUM PrP or >5 MUM Abeta1-42, with the exception of TGF-beta1 secretion, which continued to increase gradually. Overall, the results of this study indicate that these two peptides may mutually inhibit microglial chemotaxis and proliferation simultaneously via changes induced at the protein level. PMID- 24222376 TI - Nesfatin-1 decreases excitability of dopaminergic neurons in the substantia nigra. AB - Nesfatin-1, a newly discovered satiety molecule which reduces feeding behavior, has been recognized as a unique regulatory neuropeptide with its multiple roles, both central and peripheral. However, whether it had neuronal modulation effect on dopaminergic neurons is largely unknown. In the present study, using whole cell patch clamp under current-clamp mode, we investigate the effects of nesfatin 1 on the electrical activity of rat nigral dopaminergic neurons. Nesfatin-1 could produce a resting membrane potential hyperpolarization on the majority of dopaminergic neurons tested. The spike frequency decreased by 23.13 +/- 5.93 and 43.20 +/- 5.56 % in 5-nM and 10-nM nesfatin-1 groups, respectively. These effects persisted in the presence of ionotropic glutamate and GABA receptor antagonists. Our study suggests that nesfatin-1 postsynaptically inhibits the electrical activity of nigral dopaminergic neurons. PMID- 24222377 TI - Water-resistant, solid-state, dye-sensitized solar cells based on hydrophobic organic ionic plastic crystal electrolytes. AB - Water-resistant, solid-state, dye-sensitized solar cells with excellent long-term stability at 100% relative humidity and at 50 degrees C are fabricated on the basis of a novel hydrophobic organic ionic plastic crystal electrolyte and hybrid redox couple. PMID- 24222379 TI - Neutron diffraction evidence for kinetic arrest of first order magneto structural phase transitions in some functional magnetic materials. AB - Neutron diffraction measurements, performed in the presence of an external magnetic field, have been used to show structural evidence for the kinetic arrest of the first order phase transition from (i) the high temperature austenite phase to the low temperature martensite phase in the magnetic shape memory alloy Ni37Co11Mn42.5Sn9.5, (ii) the higher temperature ferromagnetic phase to the lower temperature antiferromagnetic phase in the half-doped charge ordered compound La0.5Ca0.5MnO3 and (iii) the formation of glass-like arrested states in both compounds. The cooling and heating under unequal fields protocol has been used to establish phase coexistence of metastable and equilibrium states, and also to demonstrate the devitrification of the arrested metastable states in the neutron diffraction patterns. We also explore the field-temperature dependent kinetic arrest line TK(H), through the transformation of the arrested phase to the equilibrium phase. This transformation has been observed isothermally in reducing H, as also on warming in constant H. TK is seen to increase as H increases in both cases, consistent with the low-T equilibrium phase having lower magnetization. PMID- 24222378 TI - Parental problem-solving abilities and the association of sickle cell disease complications with health-related quality of life for school-age children. AB - Children with sickle cell disease (SCD) are at risk for poor health-related quality of life (HRQOL). The current analysis sought to explore parent problem solving abilities/skills as a moderator between SCD complications and HRQOL to evaluate applicability to pediatric SCD. At baseline, 83 children ages 6-12 years and their primary caregiver completed measures of child HRQOL. Primary caregivers also completed a measure of social problem-solving. A SCD complications score was computed from medical record review. Parent problem-solving abilities significantly moderated the association of SCD complications with child self report psychosocial HRQOL (p = .006). SCD complications had a direct effect on parent proxy physical and psychosocial child HRQOL. Enhancing parent problem solving abilities may be one approach to improve HRQOL for children with high SCD complications; however, modification of parent perceptions of HRQOL may require direct intervention to improve knowledge and skills involved in disease management. PMID- 24222380 TI - Multiscale simulation of pollution gases adsorption in porous organic cage CC3. AB - A general multiscale simulation procedure is proposed to accurately predict the uptakes of pollution gases such as CO2, SO2, H2S, and CO in one of the most investigated porous organic cages CC3 by using a sophisticated force field vdW3 fitted by double hybrid functional (B2PLYP) with a dispersion correction (D3) separately for gas-gas and CC3-gas interactions. The fitted vdW3 was used in grand canonical Monte Carlo simulations. Good comparison with the coupled cluster single and double excitation and the perturbative triples (CCSD(T))/complete basis set (CBS) limit interaction energies make the B2PLYP-D3 results reliable for our purpose. The good agreement of simulated CO2 loading with experimental one and the low deviation in the fitting procedure for H2S and CO make our approach available in predicting gases in novel porous materials. PMID- 24222382 TI - A general "surface-locking" approach toward fast assembly and processing of large sized, ordered, mesoporous carbon microspheres. AB - Drying to meet you: Using microfluidic jet spray drying technology in conjunction with the evaporation-induced self-assembly strategy gives fast assembly (2 s) of mesoporous carbon microspheres. The key feature of the drying is the formation of a rigid silica crust which locks the particle size and shape. PMID- 24222381 TI - CD11c+ cells primed with unrelated antigens facilitate an accelerated immune response to influenza virus in mice. AB - Recent evidence suggests that an individual's unique history and sequence of exposures to pathogens and antigens may dictate downstream immune responses to disparate antigens. We show that the i.n. delivery of nonreplicative virus-like particles (VLPs), which bear structural but no antigenic similarities to respiratory pathogens, acts to prime the lungs of both C56BL/6 and BALB/c mice, facilitating heightened and accelerated primary immune responses to high-dose influenza challenge, thus providing a nonpathogenic model of innate imprinting. These responses correspond closely to those observed following natural infection with the opportunistic fungus, Pneumocystis murina, and are characterized by accelerated antigen processing by DCs and alveolar macrophages, an enhanced influx of cells to the local tracheobronchial lymph node, and early upregulation of T-cell co-stimulatory/adhesion molecules. CD11c+ cells, which have been directly exposed to VLPs or Pneumocystis are necessary in facilitating enhanced clearance of influenza virus, and the repopulation of the lung by Ly-6C+ precursors relies on CCR2 expression. Thus, immune imprinting 72 h after VLP priming, or 2 weeks after Pneumocystis-priming is CCR2-mediated and results from the enhanced antigen processing, maturation, and trafficking abilities of DCs and alveolar macrophages, which cause accelerated influenza-specific primary immune responses and result in superior viral clearance. PMID- 24222383 TI - Homeopathy for treatment of irritable bowel syndrome. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. Evidence based treatment guidelines have not been able to give guidance on the effects of homeopathic treatment for IBS because no systematic reviews have been carried out to assess the effectiveness of homeopathic treatment for IBS. Two types of homeopathic treatment were evaluated in this systematic review. In clinical homeopathy a specific remedy is prescribed for a specific condition. This differs from individualised homeopathic treatment, where a homeopathic remedy based on a person's individual symptoms is prescribed after a detailed consultation. OBJECTIVES: To assess the effectiveness and safety of homeopathic treatment for treating IBS. SEARCH METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), Cochrane IBD/FBD Group Specialised Register, Cochrane Complementary Medicine Field Specialised Register and the database of the Homeopathic Library (Hom inform) from inception to February 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs), cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care, in adults with IBS were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. The primary outcome was global improvement in IBS. The overall quality of the evidence supporting this outcome was assessed using the GRADE criteria. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous outcomes and the risk ratio (RR) and 95% CI for dichotomous outcomes. MAIN RESULTS: Three RCTs (213 participants) were included. No cohort or case-control studies were identified. Two studies published in 1976 and 1979 compared clinical homeopathy (homeopathic remedy) to placebo for constipation-predominant IBS. One study published in 1990 compared individualised homeopathic treatment (consultation plus remedy) to usual care (defined as high doses of dicyclomine hydrochloride, faecal bulking agents and diet sheets asking the patient to take a high fibre diet) for the treatment of IBS in female patients. Due to the low quality of reporting in the included studies the risk of bias in all three studies was unclear on most criteria and high for some criteria. A meta-analysis of two small studies (129 participants with constipation-predominant IBS) found a statistically significant difference in global improvement between the homeopathic remedy asafoetida and placebo at a short-term follow-up of two weeks. Seventy-three per cent of patients in the homeopathy group improved compared to 45% of placebo patients (RR 1.61, 95% CI 1.18 to 2.18). There was no statistically significant difference in global improvement between the homeopathic remedies asafoetida plus nux vomica and placebo. Sixty-eight per cent of patients in the homeopathy group improved compared to 52% of placebo patients (1 study, N = 42, RR 1.31, 95% CI 0.80 to 2.15). GRADE analyses rated the overall quality of the evidence for the outcome global improvement as very low due to high or unknown risk of bias, short-term follow-up and sparse data. There was no statistically significant difference found between individualised homeopathic treatment and usual care (1 RCT, N = 20) for the outcome "feeling unwell", where the participant scored how "unwell" they felt before, and after treatment (MD 0.03; 95% CI -3.16 to 3.22). None of the included studies reported on adverse events. AUTHORS' CONCLUSIONS: A pooled analysis of two small studies suggests a possible benefit for clinical homeopathy, using the remedy asafoetida, over placebo for people with constipation-predominant IBS. These results should be interpreted with caution due to the low quality of reporting in these trials, high or unknown risk of bias, short-term follow-up, and sparse data. One small study found no statistically difference between individualised homeopathy and usual care (defined as high doses of dicyclomine hydrochloride, faecal bulking agents and diet sheets advising a high fibre diet). No conclusions can be drawn from this study due to the low number of participants and the high risk of bias in this trial. In addition, it is likely that usual care has changed since this trial was conducted. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy compared to placebo or usual care. PMID- 24222384 TI - Abnormal salience network in normal aging and in amnestic mild cognitive impairment and Alzheimer's disease. AB - The salience network (SN) serves to identify salient stimuli and to switch between the central executive network (CEN) and the default-mode network (DMN), both of which are impaired in Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI). We hypothesized that both the structural and functional organization of the SN and functional interactions between the SN and CEN/DMN are altered in normal aging and in AD/aMCI. Gray matter volume (GMV) and resting state functional connectivity (FC) were analyzed from healthy younger (HYC) to older controls (HOC) and from HOC to aMCI and AD patients. All the SN components showed significant differences in the GMV, intranetwork FC, and internetwork FC between the HYC and HOC. Most of the SN components showed differences in the GMV between the HOC and AD and between the aMCI and AD. Compared with the HOC, AD patients exhibited significant differences in intra- and internetwork FCs of the SN, whereas aMCI patients demonstrated differences in internetwork FC of the SN. Most of the GMVs and internetwork FCs of the SN and part of the intranetwork FC of the SN were correlated with cognitive differences in older subjects. Our findings suggested that structural and functional impairments of the SN may occur as early as in normal aging and that functional disconnection between the SN and CEN/ DMN may also be associated with both normal aging and disease progression. PMID- 24222386 TI - Obesity increases heart disease risk in absence of metabolic risk factors. PMID- 24222385 TI - Enhanced cardioprotective effects mediated by plasmid containing the short hairpin RNA of angiotensin converting enzyme with a biodegradable hydrogel after myocardial infarction. AB - The expression of foreign gene was enhanced and prolonged by sustained releasing a target gene to cells from biodegradable dextran-poly(e-caprolactone)-2 hydroxylethylmethacrylate-poly(N-isopropylacrylamide) (Dex-PCL-HEMA/PNIPAAm) hydrogel in vitro. Moreover, we have demonstrated that injection of the same hydrogel improved post-infarct ventricular remodeling. Therefore, we hypothesized that intramyocardial injection of plasmid containing the short-hairpin RNA (shRNA) of angiotensin converting enzyme (ACE) with the same hydrogel enhances the cardioprotective effects superior to either alone or after rat myocardial infarction (MI). In this study, equal volume of phosphate-buffered solution (PBS), 10 MUg ACE-shRNA plasmids, hydrogel containing 10 MUg negative control ACE shRNA plasmids and hydrogel containing 10 MUg ACE-shRNA plasmids were shortly injected into the infarct area of rats after MI, respectively. We found that ACE shRNA plasmid-loaded hydrogel extended the duration of gene expression in vivo. Moreover, it was shown that direct intramyocardial injection of ACE-shRNA plasmid loaded hydrogel significantly decreased the expression of local ACE expression, inhibited cell apoptosis, reduced infarct size, and improved cardiac function compared with the injection of either alone 30 days after MI in rats. These results suggest that injection of ACE-shRNA plasmid-loaded hydrogel into impaired myocardium obtains more cardioprotective effects than either alone in rat with MI by prolonging the gene silencing of ACE. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3452-3458, 2014. PMID- 24222387 TI - Magnetocaloric effect and critical behaviour in Mn2-pyridazine-[Nb(CN)8] molecular compound under press. AB - A comprehensive study of magnetocaloric effect (MCE) and critical behaviour in the ferrimagnetic Mn2-pyridazine-[Nb(CN)8] molecular magnet under hydrostatic pressure is reported. The pressure-induced structural changes provoke the strengthening of magnetic interaction between Mn and Nb centres. Consequently, an increase of critical temperature Tc is observed from 43 K for a sample at ambient pressure (A) to 52.5 K for a sample under a pressure of 1.19 GPa (AHP). The magnetocaloric effect was determined by the magnetization measurements. The application of a hydrostatic pressure of 1.19 GPa causes a decrease in the maximum value of magnetic entropy change DeltaS, which for AHP is equal to 4.63 J mol-1 K-1 (7.73 J kg-1 K-1) at MU0DeltaH = 5 T, while for A it is 5.36 J mol-1 K 1 (8.95 J kg-1 K-1) for the same magnetic field change. The temperature-dependent parameter n obtained for AHP, describing the field dependence of MCE, is consistent with other critical exponents determined from magnetization measurements. The critical exponents allow us to classify AHP to the 3D Heisenberg universality class, similar to the case of the non-pressurized sample. PMID- 24222388 TI - The 3rd Transatlantic Frontiers in Chemistry Symposium. PMID- 24222391 TI - Three-pronged probes: high-affinity DNA binding with cap, beta-alanines and oligopyrrolamides. PMID- 24222392 TI - Valence-to-core X-ray emission spectroscopy of iron-carbonyl complexes: implications for the examination of catalytic intermediates. AB - Valence-to-core X-ray emission spectroscopy (V2C XES) has been applied to a series of compounds relevant to both homogeneous catalysts and intermediates in heterogeneous reactions, namely [Fe(CO)5], [Fe2(CO)9], [Fe3(CO)12], [Fe(CO)3(cod)] (cod=cyclo-octadienyl), [Fe2Cp2(CO)4] (Cp=cyclo-pentadienyl), [Fe2Cp*2(CO)4] (Cp*=tetramethylcyclopentadienyl), and [FeCp(CO)2(thf)][B(ArF)4] (ArF=pentafluorophenyl). DFT calculations of the V2C XES spectra show very good agreement with experiment, which allows for an in depth analysis of the origins of the observed spectral signatures. It is demonstrated that the observed spectral features can be broken down into specific ligand and metal fragment contributions. The relative intensities of the observed features are further explained through a quantitative investigation of the metal 3p and 4p contributions to the spectra. The ability to use V2C XES to separate carbonyl, hydrocarbon, and solvent contributions is highlighted. PMID- 24222393 TI - Cyclometalated iridium(III) complexes with deoxyribose substituents. AB - Fundamental study of enzymatic nucleoside transport suffers for lack of optical probes that can be tracked noninvasively. Nucleoside transporters are integral membrane glycoproteins that mediate the salvage of nucleosides and their passage across cell membranes. The substrate recognition site is the deoxyribose sugar, often with little distinction among nucleobases. Reported here are nucleoside analogues in which emissive, cyclometalated iridium(III) complexes are "clicked" to C-1 of deoxyribose in place of canonical nucleobases. The resulting complexes show visible luminescence at room temperature and 77 K with microsecond-length triplet lifetimes. A representative complex is crystallographically characterized. Transport and luminescence are demonstrated in cultured human carcinoma (KB3-1) cells. PMID- 24222394 TI - Male aggression against women : An evolutionary perspective. AB - Male aggression against females in primates, including humans, often functions to control female sexuality to the male's reproductive advantage. A comparative, evolutionary perspective is used to generate several hypotheses to help to explain cross-cultural variation in the frequency of male aggression against women. Variables considered include protection of women by kin, male-male alliances and male strategies for guarding mates and obtaining adulterous matings, and male resource control. The relationships between male aggression against women and gender ideologies, male domination of women, and female sexuality are also considered. PMID- 24222395 TI - Women's strategies in polygynous marriage : Kipsigis, Datoga, and other East African cases. AB - Both behavioral ecological and social anthropological analyses of polygynous marriage tend to emphasize the importance of competition among men in acquisition of mates, whereas the strategic options to women both prior to and after the establishment of a marriage have been neglected. Focusing on African marriage systems that are in some senses analogous to resource-defense polygyny, I first review the evidence of reproductive costs of polygyny to women. Then I discuss why the conflict of interests between men and women over mate number is often likely to be settled in favor of men. Using East African ethnographic data I examine the strategic responses of women and their families to polygynous marriage, focusing on four topics: mate choice (Kipsigis), attitudes toward incoming wives (Kipsigis), labor allocation and cooperation (comparative data, Kipsigis), and use of parental wealth (Datoga). The results of these quantitative analyses suggest that through a combination of judicious marriage choice and strategic responses within marriage, polygyny need not be costly to women in resource-defense polygynous systems. The conclusion is that a hierarchy of questions need to be addressed in the analysis of any polygynous marriage system. PMID- 24222396 TI - Phylogenetic fallacies and sexual oppression : A review article onPedophilia: Biosocial Dimensions, Jay R. Feierman, ed. New York: Springer Verlag, 1990. PMID- 24222397 TI - Obstetricians and gynecologists' practice and opinions of expanded carrier testing and noninvasive prenatal testing. AB - OBJECTIVE: The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of >100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT). METHODS: A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight. RESULTS: Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight. CONCLUSION: Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs. PMID- 24222398 TI - 2-Aminobenzaldehydes as versatile substrates for rhodium-catalyzed alkyne hydroacylation: application to dihydroquinolone synthesis. PMID- 24222399 TI - Magnesium degradation products: effects on tissue and human metabolism. AB - Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account. PMID- 24222401 TI - The function of menstrual taboos among the dogon : Defense against Cuckoldry? AB - Menstrual taboos are nearly ubiquitous and assume parallel forms in geographically distant populations, yet their function has baffled researchers for decades. This paper proposes that menstrual taboos are anticuckoldry tactics. By signaling menstruation, they may advertise female reproductive status to husbands, affines, and other observers. Females may therefore have difficulty in obfuscating the timing of the onset of pregnancy. This may have three consequences: (a) males are better able to assess their probabilities of paternity and to direct their parental investment toward genetic offspring; (b) adulterous pregnancies are more easily detected and penalized, enhancing sexual fidelity; and (c) males avoid marrying pregnant females by relying on menstruation as evidence of nonpregnancy. This hypothesis is tested with 29 months of field data on menstrual taboos among the Dogon of Mali. Key results include the following: (a) cuckoldry is a major Dogon concern, (b) menstrual huts advertise female reproductive status, (c) husbands impose the taboos upon their wives, (d) female defiance of the taboos is undetectable and probably rare, and (e) informants think that the taboos help husbands and patrilineages to avoid cuckoldry. Thus the anti-cuckoldry hypothesis provides helpful insight into the menstrual taboos of the Dogon and should be tested among other populations. PMID- 24222400 TI - Diagnostic accuracy of random massively parallel sequencing for non-invasive prenatal detection of common autosomal aneuploidies: a collaborative study in Europe. AB - OBJECTIVE: The objective of this study is to validate the diagnostic accuracy of a non-invasive prenatal test for detecting trisomies 13, 18, and 21 for a population in Germany and Switzerland. METHODS: Random massively parallel sequencing was applied using Illumina sequencing platform HiSeq2000. Fetal aneuploidies were identified using a median absolute deviation based z-score equation. A bioinformatics algorithm based on guanine-cytosine normalization was applied after the data were unblinded. Results of massively parallel sequencing and invasive procedures were compared. RESULTS: Overall, 40/42 samples were correctly classified as trisomy 21-positive, including a translocation trisomy 21 [46,XY,der(13;21),+21] and a structural aberration of chromosome 21 [46,XX,rec(21)dup(21q)inv(21)(p12q21.1)] but not including a low percentage mosaic trisomy 21 [47,XY,+21/46,XY], [sensitivity: 95.2%; one-sided lower confidence limit: 85.8%]; 430/430 samples were correctly classified as trisomy 21 negative (specificity: 100%; one-sided lower CL: 99.3%). Using a new bioinformatics algorithm with guanine-cytosine normalization, detection of trisomy 21 was facilitated, and five of five trisomy 13 cases and eight of eight trisomy 18 cases were correctly identified. CONCLUSION: Our newly established non invasive prenatal test allows detection of fetal trisomies 13, 18, and 21 with high accuracy in a population in Germany and Switzerland. PMID- 24222402 TI - The evolution of female sexuality and mate selection in humans. AB - Understanding female sexuality and mate choice is central to evolutionary scenarios of human social systems. Studies of female sexuality conducted by sex researchers in the United States since 1938 indicate that human females in general are concerned with their sexual well-being and are capable of sexual response parallel to that of males. Across cultures in general and in western societies in particular, females engage in extramarital affairs regularly, regardless of punishment by males or social disapproval. Families are usually concerned with marriage arrangements only insofar as those arrangements are economically or politically advantageous, but females most often have a voice in arranged marriages. Extended families also concentrate on a couple's future reproduction rather than on sexual exclusivity. Although marriage for females is often compromised by male or family reproductive interests (which may not in fact differ from female interests), females appear to exercise their sexuality with more freedom than has previously been suggested. Notions of human females as pawns in the male reproductive game, or as traders of sex for male services, should be dispelled. PMID- 24222403 TI - The question of animal culture. AB - In this paper I consider whether traditional behaviors of animals, like traditions of humans, are transmitted by imitation learning. Review of the literature on problem solving by captive primates, and detailed consideration of two widely cited instances of purported learning by imitation and of culture in free-living primates (sweet-potato washing by Japanese macaques and termite fishing by chimpanzees), suggests that nonhuman primates do not learn to solve problems by imitation. It may, therefore, be misleading to treat animal traditions and human culture as homologous (rather than analogous) and to refer to animal traditions as cultural. PMID- 24222404 TI - A reply to Rogers : Conserving resources for children. PMID- 24222405 TI - Translating working memory into action: behavioral and neural evidence for using motor representations in encoding visuo-spatial sequences. AB - The neurobiological organization of action-oriented working memory is not well understood. To elucidate the neural correlates of translating visuo-spatial stimulus sequences into delayed (memory-guided) sequential actions, we measured brain activity using functional magnetic resonance imaging while participants encoded sequences of four to seven dots appearing on fingers of a left or right schematic hand. After variable delays, sequences were to be reproduced with the corresponding fingers. Recall became less accurate with longer sequences and was initiated faster after long delays. Across both hands, encoding and recall activated bilateral prefrontal, premotor, superior and inferior parietal regions as well as the basal ganglia, whereas hand-specific activity was found (albeit to a lesser degree during encoding) in contralateral premotor, sensorimotor, and superior parietal cortex. Activation differences after long versus short delays were restricted to motor-related regions, indicating that rehearsal during long delays might have facilitated the conversion of the memorandum into concrete motor programs at recall. Furthermore, basal ganglia activity during encoding selectively predicted correct recall. Taken together, the results suggest that to be-reproduced visuo-spatial sequences are encoded as prospective action representations (motor intentions), possibly in addition to retrospective sensory codes. Overall, our study supports and extends multi-component models of working memory, highlighting the notion that sensory input can be coded in multiple ways depending on what the memorandum is to be used for. PMID- 24222406 TI - Application of metabolic flux analysis to plants. AB - This volume compiles a series of chapters that cover the major aspects of plant metabolic flux analysis, such as but not limited to labeling of plant material, acquisition of labeling data, mathematical modeling of metabolic network at the cell, tissue, and plant level. A short revue, including methodological points and applications of flux analysis to plants, is presented in this introductory chapter. PMID- 24222407 TI - Metabolic network reconstruction and their topological analysis. AB - This chapter focuses on the way to build a metabolic network and how to analyze its structure. The first part of this chapter describes the methods of the network model reconstruction from biochemical data found in specialized databases and/or literature. The second part deals with metabolic pathway analysis as a useful tool for better understanding the complex architecture of intracellular metabolism. The graph analysis and the stoichiometric network analysis are important approaches for understanding the network topology and consequently the function of metabolic networks. Among the methods presented, the Elementary Flux Modes analysis will be more detailed. Finally, we illustrate in this chapter an example of network reconstruction from heterotrophic plant cells metabolism and its topological analysis leading to a huge number of Elementary Flux Modes. PMID- 24222408 TI - 14C pulse labeling to estimate external fluxes and turnovers in primary metabolism. AB - Steady state (13)C-MFA is classically used to measure fluxes in complex metabolic networks. However, the modeling of steady state labeling allows the quantification of internal fluxes only and requires the estimation, by other methods, of the external fluxes, corresponding to substrate uptake (carbon input into the network) and to the production rate of compounds that accumulate within plant cells (network output). Additionally, it is not always possible to discriminate between different pathways that lead to the same label distribution. Methods to measure fluxes, based on direct measurements of pool size and on (14)C short-time labeling experiments, are described in this chapter. To illustrate this approach, we focus on the quantification of sucrose and starch turnovers. PMID- 24222409 TI - Optimization of steady-state 13C-labeling experiments for metabolic flux analysis. AB - While steady-state (13)C metabolic flux analysis is a powerful method for deducing multiple fluxes in the central metabolic network of heterotrophic and mixotrophic plant tissues, it is also time-consuming and technically challenging. Key steps in the design and interpretation of steady-state (13)C labeling experiments are illustrated with a generic protocol based on applications to plant cell suspension cultures. PMID- 24222410 TI - Quantification of 13C enrichments and isotopomer abundances for metabolic flux analysis using 1D NMR spectroscopy. AB - The analysis of stable isotope incorporation following feeding of (13)C-labeled precursors to plant tissues provides the constraints necessary for metabolic flux analysis. This protocol describes the use of one-dimensional (1)H and (13)C nuclear magnetic resonance spectroscopy for the quantification of (13)C enrichments and isotopomer abundances in mixtures of metabolites or hydrolyzed biomass components. PMID- 24222411 TI - Analysis of proteinogenic amino acid and starch labeling by 2D NMR. AB - Comprehensive analysis of isotopic labeling patterns of metabolites in proteinogenic amino acids and starch for plant systems lay in the powerful tool of 2-Dimensional [(1)H, (13)C] Nuclear Magnetic Resonance (2D NMR) spectroscopy. From (13)C-labeling experiments, 2D NMR provides information on the labeling of particular carbon positions, which contributes to the quantification of positional isotope isomers (isotopomer). 2D Heteronuclear Single Quantum Correlation (HSQC) NMR distinguishes particularly between the labeling patterns of adjacent carbon atoms, and leads to a characteristic enrichment of each carbon atom of amino acids and glucosyl and mannosyl units present in hydrolysates of glycosylated protein. Furthermore, this technique can quantitatively classify differences in glucosyl units of starch hydrolysate and of protein hydrolysate of plant biomass. Therefore, the 2D HSQC NMR method uses proteinogenic amino acids and starch to provide an understanding of carbon distribution of compartmentalization in the plant system. NMR has the advantage of minimal sample handle without separate individual compounds prior to analysis, for example multiple isotopomers can be detected, and their distribution extracted quantitatively from a single 2D HSQC NMR spectrum. The peak structure obtained from the HSQC experiment show multiplet patterns, which are directly related to isotopomer balancing. These abundances can be translated to maximum information on the metabolic flux analysis. Detailed methods for the extractions of protein, oil, soluble sugars, and starch, hydrolysis of proteinogenic amino acid and starch, and NMR preparation using soybean embryos cultured in vitro as a model plant systems are reported in this text. In addition, this chapter includes procedures to obtain the relative intensity of 16 amino acids and glucosyl units from protein hydrolysate and the glucosyl units of starch hydrolysate of soybean embryos in 2D HSQC NMR spectra. PMID- 24222412 TI - Analysis of kinetic labeling of amino acids and organic acids by GC-MS. AB - Plant metabolic pathways and the molecular and atomic fluxes through them can be deduced using stable isotopically labeled substrates. To this end one prerequisite is accurate measurement of the labeling pattern of targeted metabolites. Experiments are generally limited to the use of single-element isotopes, mainly (13)C. Here, we summarize the application of gas chromatography time of flight mass spectrometry (GC-TOF-MS) for metabolic studies using differently labeled elemental isotopes applied to both intact organelles and whole plant tissue. This method allows quantitative evaluation of a broad range of metabolic pathways without the need for laborious (and potentially inaccurate) chemical fractionation procedures commonly used in the estimation of fluxes following incubation in radiolabeled substrates. We focus herein on the determination of isotope labeling in organic and amino acids. PMID- 24222413 TI - Quantifying 13C-labeling in free sugars and starch by GC-MS. AB - We describe an approach to extract (13)C-labeled sugars (glucose, fructose, maltose, sucrose, myo-inositol as well as glucose from starch) from plant tissues and to analyze their isotopomer distribution by gas chromatography-mass spectrometry (GC-MS). Sugars are derivatized with N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) into their Si(CH3)3 derivatives. Electronic and chemical ionizations are used to obtain suitable fragments for metabolic flux analysis (MFA). Unique fragments are identified by computer simulation and experimental verification with labeled standards. Linear equations for separating information from glucosyl and fructosyl moieties of sucrose are presented. Finally, mass distributions are corrected for natural isotope abundance using a home-written program. The method is illustrated by sugar isotopomer analysis of (13)C-labeled rapeseed embryos. PMID- 24222414 TI - Liquid chromatography tandem mass spectrometry for measuring 13C-labeling in intermediates of the glycolysis and pentose phosphate pathway. AB - This chapter describes a procedure to analyze (13)C-labeled phosphorylated compounds by liquid chromatography tandem mass spectrometry. Phosphorylated compounds, intermediaries of the glycolysis and pentose phosphate pathway, are separated by anion exchange chromatography and their isotopic labeling is determined by mass spectrometry. A sensitivity in the fmole range is achieved using scheduled multiple reaction monitoring mode. PMID- 24222415 TI - In vivo NMR for 13C Metabolic Flux Analysis. AB - The use of in vivo NMR within the framework of Metabolic Flux Analysis in plants is presented. In vivo NMR allows to visualize the active metabolic network, to determine metabolic and isotopic steady state and to measure metabolic fluxes which are not necessarily accessible by isotopic steady state (stationary) Metabolic Flux Analysis. The kinetic data can be used as input for dynamic (nonstationary) Metabolic Flux Analysis. Both 1D and 2D NMR methods are employed. PMID- 24222416 TI - Steady-state and instationary modeling of proteinogenic and free amino acid isotopomers for flux quantification. AB - Metabolic flux analysis (MFA) is a powerful tool for exploring and quantifying carbon traffic in metabolic networks. Accurate flux quantification requires (1) high-quality isotopomer measurements, usually of biomass components including proteinogenic/free amino acids or central carbon metabolites, and (2) a mathematical model that relates the unknown fluxes to the measured isotopomers. Modeling requires a thorough knowledge of the structure of the underlying metabolic network, often available from many databases, as well as the ability to make reasonable assumptions that will enable simplification of the model. Here we describe a general methodology underlying computer-aided mathematical modeling of a flux-isotopomer relationship and some of the accompanying data-processing steps. One of two modeling strategies will need to be employed, depending on the type of isotope labeling experiment performed. These strategies-steady-state modeling and instationary modeling-have different experimental and computational demands. We discuss the concepts underlying these two types of modeling and demonstrate steady-state modeling in a step-by-step manner. Our methodology should be applicable to most isotope-assisted MFA applications and should serve as a general framework applicable to many realistic metabolic networks with little modification. PMID- 24222417 TI - Isotopically nonstationary MFA (INST-MFA) of autotrophic metabolism. AB - Metabolic flux analysis (MFA) is a powerful approach for quantifying plant central carbon metabolism based upon a combination of extracellular flux measurements and intracellular isotope labeling measurements. In this chapter, we present the method of isotopically nonstationary (13)C MFA (INST-MFA), which is applicable to autotrophic systems that are at metabolic steady state but are sampled during the transient period prior to achieving isotopic steady state following the introduction of (13)CO2. We describe protocols for performing the necessary isotope labeling experiments, sample collection and quenching, nonaqueous fractionation and extraction of intracellular metabolites, and mass spectrometry (MS) analysis of metabolite labeling. We also outline the steps required to perform computational flux estimation using INST-MFA. By combining several recently developed experimental and computational techniques, INST-MFA provides an important new platform for mapping carbon fluxes that is especially applicable to autotrophic organisms, which are not amenable to steady-state (13)C MFA experiments. PMID- 24222418 TI - Simulating labeling to estimate kinetic parameters for flux control analysis. AB - An important aspect of kinetic modeling is the ability to provide predictive information on network control and dynamic responses to genetic or environmental perturbations based on innate enzyme kinetics. In a top-down approach to model assembly, unknown kinetic parameters are calculated using experimental data such as metabolite pool concentrations and transient labeling patterns after supply of an isotopically labeled substrate. These kinetic parameters can then be used to calculate flux control coefficients for every reaction in a network, which aids in the identification of enzymatic reactions that exert the most control over the network as a whole. This chapter describes a modeling approach to estimate kinetic parameters which are then used to perform metabolic control analysis. An example is provided for the benzenoid network of Petunia hybrida; however, the methodologies can be applied to any small segment of metabolism. PMID- 24222419 TI - High-throughput data pipelines for metabolic flux analysis in plants. AB - In this chapter we illustrate the methodology for high-throughput metabolic flux analysis. Central to this is developing an end to end data pipeline, crucial for integrating the wet lab experiments and analytics, combining hardware and software automation, and standardizing data representation providing importers and exporters to support third party tools. The use of existing software at the start, data extraction from the chromatogram, and the end, MFA analysis, allows for the most flexibility in this workflow. Developing iMS2Flux provided a standard, extensible, platform independent tool to act as the "glue" between these end points. Most importantly this tool can be easily adapted to support different data formats, data verification and data correction steps allowing it to be central to managing the data necessary for high-throughput MFA. An additional tool was needed to automate the MFA software and in particular to take advantage of the course grained parallel nature of high-throughput analysis and available high performance computing facilities.In combination these methods show the development of high-throughput pipelines that allow metabolic flux analysis to join as a full member of the omics family. PMID- 24222420 TI - Analysis of enzyme activities. AB - The evaluation of enzyme activities, especially their capacities, represents an important step towards the modelling of biochemical pathways in living organisms. The implementation of microplate technology enables the determination of up to >50 enzymes in relatively large numbers of samples and in various biological materials. Most of these enzymes are involved in central metabolism and several pathways are entirely covered. Direct or indirect assays can be used, as well as highly sensitive assays, depending on the abundance of the enzymes under study. To exemplify such methods, protocols for UDP-glucose pyrophosphorylase (E.C. 2.7.7.9) operating in real time and for pyrophosphate:fructose-6-phosphate 1 phosphotransferase (E.C. 2.7.1.90) are presented. PMID- 24222421 TI - Analytical kinetic modeling: a practical procedure. AB - This chapter describes a practical procedure to dissect metabolic systems, simplify them, and use or derive enzyme rate equations in order to build a mathematical model of a metabolic system and run simulations. We first deal with a simple example, modeling a single enzyme that follows Michaelis-Menten kinetics and operates in the middle of an unbranched metabolic pathway. Next we describe the rules that can be followed to isolate sub-systems from their environment to simulate their behavior. Finally we use examples to show how to derive suitable rate equations, simpler than those needed for mechanistic studies, though adequate to describe the behavior over the physiological range of conditions.Many of the general characteristics of kinetic models will be obvious to readers familiar with the theory of metabolic control analysis (Cornish-Bowden, Fundamentals of Enzyme Kinetics, Wiley-Blackwell, Weinheim, 327-380, 2012), but here we shall not assume such knowledge, as the chapter is directed toward practical application rather than theory. PMID- 24222422 TI - Flux balance analysis as an alternative method to estimate fluxes without labeling. AB - The analysis of plant metabolic networks essentially contributes to the understanding of the efficiency of plant systems in terms of their biotechnological usage. Metabolic fluxes are determined by biochemical parameters such as metabolite concentrations as well as enzyme properties and activities, which in turn are the result of various regulatory events at various levels between control of transcription and posttranslational regulation of enzyme protein activity. Thus, knowledge about metabolic fluxes on a large scale provides an integrated view on the functional state of a metabolically active cell, organ, or system. In this chapter, we introduce flux balance analysis as a constraint-based method for the prediction of optimal metabolic fluxes in a given metabolic network. Furthermore, we provide a step-by-step protocol for metabolic network reconstruction and constraint-based analysis using the COBRA Toolbox. PMID- 24222423 TI - Flux variability analysis: application to developing oilseed rape embryos using toolboxes for constraint-based modeling. AB - Flux variability analysis enables comprehensive exploration of alternate optimal routes in a metabolic network. This method is especially useful with models such as bna572 for the developing oilseed rape embryo which is highly compartmentalized. Here, we describe a protocol for carrying out flux variability analysis on reactions and network projections of bna572 using well-established software (CellNetAnalyzer and COBRA) for constraint-based analysis of stoichiometric network reconstructions. PMID- 24222424 TI - Plant genome-scale modeling and implementation. AB - Considerable progress has been made in plant genome-scale metabolic reconstruction and modeling in recent years. Such reconstructions made it possible to explore metabolic phenotypes through appropriate model formulation and optimization methods. As a result, plant genome-scale modeling has increasingly attracted interest from the plant research community. In this chapter, the first generation of plant genome-scale metabolic reconstructions is presented, along with the important concepts behind model and constraint formulation. A brief protocol describing the use of constraint-based reconstruction and analysis (COBRA) Toolbox in flux simulation and model modification is provided. This is followed by a presentation of metabolic constraints required to generate fluxes in AraGEM using COBRA that describe photosynthesis, photorespiration, and respiration, respectively. Overall, plant genome-scale modeling is a powerful approach that is accessible and readily adopted. PMID- 24222425 TI - (34)S and (15)N labelling to model S and N flux in plants and determine the different components of N and S use efficiency. AB - In order to highlight our understanding on ecosystems functioning and resource sharing/competition, either in artificial environment or agrosystems, according to changes in the climatic conditions, it is necessary to measure accurately element fluxes within plants. Stable isotopes allow tracking safely and accurately on a short time frame the behavior of elements in plants. After a short review devoted to isotopic studies of elemental flux within plants, we explain how a direct multiple labelling study might be conducted in a plant, so as to measure over short time nitrogen and sulfur acquisition, and assimilates arising from a labelled source. PMID- 24222426 TI - Ecophysiological process-based model to simulate carbon fluxes in plants. AB - Carbon fluxes in plants have been subject to many modeling studies. The conceptual framework of models of carbon acquisition, allocation, and metabolism in plants are first introduced, together with methods to calibrate and evaluate the validity of the resulting models. The possibility to combine different models within an integrated plant-organ system is illustrated. In the last part of the chapter, methods used to measure the carbon flows at the plant scale are discussed. PMID- 24222427 TI - Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study. AB - Persistent cancer-related fatigue (PCRF) is one of the most troubling side effects of breast cancer (BC) treatment. One explanatory model for PCRF is sickness behavior, which is a set of adaptive responses including sleepiness and depressed mood in reaction to an inflammatory trigger. Prior research has investigated differences in inflammatory cytokines between fatigued and non fatigued BC survivors, but no study has examined differences in brain metabolites. Differences in inflammatory markers, and brain metabolites using proton magnetic resonance spectroscopy were evaluated within 16 fatigued and 13 non-fatigued BC survivors. Fatigued BC survivors had significantly higher ratios of two markers derived from brain metabolites; namely (a) creatine, normalized to total creatine (creatine + phosphocreatine (Cr/tCr)) ratio (P = 0.03) and (b) glutamate + glutamine (Glx) to N-acetyl-aspartate (NAA) ratio (P = 0.01) in the posterior insula compared to non-fatigued breast cancer survivor. Further, serum IL-6 was increased in fatigued women compared to non-fatigued women (P = 0.03), Using receiver operator curves (ROC) we determined that the posterior insula Glx/NAA ratio was the best predictor of fatigue with an overall area under the receiver operating characteristic curve (AUROC) of 79%, with a sensitivity of 81% and a specificity of 69%. However, posterior insula Glx/NAA, Cr/tCr and serum IL 6 were not significantly correlated with one another implying the possibility of independent biological mechanisms for PCRF rather than an interrelated mechanism as represented by the sickness behavior model. This study provides novel preliminary evidence of several distinct neurobiological changes in the posterior insula associated with PCRF in BC survivors. Future, longitudinal studies are needed to explore these distinct biological phenomena where changes through time in peripheral immune markers and brain metabolites are examined to determine if they correlate with changes in fatigue. PMID- 24222428 TI - Interplay of alpha,alpha- versus alpha,beta-conjugation in the excited states and charged defects of branched oligothiophenes as models for dendrimeric materials. AB - This article investigates the excited and charged states of three branched oligothiophenes with methyl-thienyl side groups as models to promote 3D arrangements. A comparison with the properties of the parent systems, linear all alpha,alpha-oligothiophenes, is proposed. A wide variety of spectroscopic methods (i.e., absorption, emission, triplet-triplet transient absorption, and spectroelectrochemistry) in combination with DFT calculations have been used for this purpose. Whereas the absorption spectra are slightly blueshifted upon branching, both the emission spectra and triplet-triplet absorption spectra are moderately redshifted; this indicates a larger contribution of the beta-linked thienyl groups in the delocalization of the S1 and T1 states rather than into the S0 state. The delocalization through the alpha,beta-conjugated path was found to be crucial for the stabilization of the trication species in the larger branched systems, whereas the linear sexithiophene homologue can only be stabilized up to the dication species. PMID- 24222429 TI - Trade-Offs between female food acquisition and child care among hiwi and ache foragers. AB - Even though female food acquisition is an area of considerable interest in hunter gatherer research, the ecological determinants of women's economic decisions in these populations are still poorly understood. The literature on female foraging behavior indicates that there is considerable variation within and across foraging societies in the amount of time that women spend foraging and in the amount and types of food that they acquire. It is possible that this heterogeneity reflects variation in the trade-offs between time spent in food acquisition and child care activities that women face in different groups of hunter-gatherers. In this paper we discuss the fitness trade-offs between food acquisition and child care that Hiwi and Ache women foragers might face. Multiple regression analyses show that in both populations the daily food acquisition of a woman's spouse is negatively related to female foraging effort. In addition, nursing mothers spend less time foraging and acquire less food than do nonnursing women. As the number of dependents that a woman has increases, however, women also increase foraging time and the amount of food they acquire. Some interesting exceptions to these general trends are as follows: (a) differences in foraging effort between nursing and nonnursing women are less pronounced when fruits and roots are in season than in other seasons of the year; (b) foraging return rates decrease for Ache women as their numbers of dependents increase; and (c) among Ache women, the positive effect of number of dependents on foraging behavior is less pronounced when fruits are in season than at other times of the year. Lastly, in the Hiwi sample we found that postreproductive women work considerably harder than women of reproductive age in the root season but not in other seasons of the year. We discuss how ecological variation in constraints, the number of health insults to children that Hiwi and Ache mothers can avoid, and the fitness benefits they can gain from spending time in food acquisition and child care might account for differences and similarities in the foraging behaviors of subgroups of Hiwi and Ache mothers across different seasons of the year. Valid tests of the explanations we propose will require considerable effort to measure the relationship between maternal food acquisition, child care, and adverse health outcomes in offspring. PMID- 24222430 TI - Evolutionary biology and feminism. AB - Evolutionary biology and feminism share a variety of philosophical and practical concerns. I have tried to describe how a perspective from both evolutionary biology and feminism can accelerate the achievement of goals for both feminists and evolutionary biologists. In an early section of this paper I discuss the importance of variation to the disciplines of evolutionary biology and feminism. In the section entitled "Control of Female Reproduction" I demonstrate how insight provided by participation in life as woman and also as a feminist suggests testable hypotheses about the evolution of social behavior-hypotheses that are applicable to our investigations of the evolution of social behavior in nonhuman animals. In the section on "Deceit, Self-deception, and Patriarchal Reversals" I have overtly conceded that evolutionary biology, a scientific discipline, also represents a human cultural practice that, like other human cultural practices, may in parts and at times be characterized by deceit and self deception. In the section on "Femininity" I have indicated how questions cast and answered and hypotheses tested from an evolutionary perspective can serve women and men struggling with sexist oppression. PMID- 24222431 TI - Sex, gender, and difference : Dimensions of aggression in an australian aboriginal community. AB - Empirical research has demonstrated that women's aggressive behavior is widespread and displays regularities across societies. Until recently, however, discussions about the aggressive behavior of women and gender differences in aggressive behavior have been based largely on data from nonhuman primates, children, or laboratory experiments. Using a unique corpus of naturalistic data on aggressive human interactions both between and among men and women, I explore the complexity of our questions about sex differences in aggression and further illuminate the ways in which men and women may use aggression in human interactions. In this paper I compare the aggressive behavior of men and women in an Australian Aboriginal community. In doing so I argue for the continuing use of a "sex differences" framework for organizing our understanding of gender relations and gender hierarchy. I believe, however, that this form of analysis benefits from, if not requires, a sensitivity to the most taken-for-granted aspects of our gender ideology and a commitment to attend to evidence that challenges our convictions about men and women. PMID- 24222432 TI - Reply to dickemann : The ethology of variant sexology. AB - This paper is a response to Dickemann's review ofPedophilia: Biosocial Dimensions. Her main criticism of the book is its inappropriate application of ethology to human sexology and its natural variations. She proposes instead the superiority of the "social constructionist" perspective. The "Phylogenetic Fallacy" of which her review speaks results from her erroneously having attributed ethological arguments about the phylogeny of coordinated motor patterns and sensory releasing stimuli to higher levels of behavioral-ecological strategies to which such arguments were never applied. Because no convincingly adaptive function of human pedophilia could be found at this higher level, as a working hypothesis, variant erotic age and gender orientations were both tentatively conceptualized as by-products of Darwinian natural selection for heterosexual "adultophilia." The social and political implications of this perspective, when compared to social constructionism, are discussed. PMID- 24222434 TI - Modifications in the frustrated magnetism, oxidation state of Co and magnetoelectric coupling effects induced by a partial replacement of Ca by Gd in the spin-chain compound Ca3Co2O6. AB - We have systematically investigated the influence of the gradual replacement of Ca by Gd on the magnetic and complex dielectric properties of the well-known geometrically frustrated spin-chain system Ca3Co2O6 (TN = 24 K with additional magnetic transitions below 12 K), by studying the series Ca3-xGdxCo2O6 (x <= 0.7), down to 1.8 K. Heat-capacity measurements establish that the reduction of TN with Gd substitution is much less compared to that by Y substitution. The magnetic moment data reveal that there are changes in the oxidation state of Co as well, unlike for Y substitution, beyond x = 0.2. Thus, despite being isovalent, both these substitutions interestingly differ in changing these magnetic properties in these oxides. We propose that the valence electrons of Y and those of R ions play different roles in deciding the magnetic characteristics of these mixed oxides. It is observed that a small amount (x = 0.3) of Gd substitution for Ca is enough to suppress glassy ac magnetic susceptibility behavior for the peak around 12 K. An additional low-temperature magnetic anomaly close to 5 K gets more prominent with increasing Gd concentration as revealed by heat-capacity data. Trends in temperature dependence of complex dielectric behavior were also tracked with varying composition and a frequency dependence is observed, not only for the transition in the region around 10 K (for some compositions), but also for the 5 K transition which is well resolved for a higher concentration of Gd. Thus, the Gd-substituted Ca3Co2O6 series is shown to reveal interesting magnetic and dielectric behaviors of this family of oxides. PMID- 24222433 TI - Prenatal diagnosis of nonsyndromic congenital heart defects. AB - OBJECTIVES: Congenital heart defects (CHDs) occur in nearly 1% of live births. We sought to assess factors associated with prenatal CHD diagnosis in the National Birth Defects Prevention Study (NBDPS). METHODS: We analyzed data from mothers with CHD-affected pregnancies from 1998 to 2005. Prenatal CHD diagnosis was defined as affirmative responses to questions about abnormal prenatal ultrasounds and fetal echocardiography obtained during a structured telephone interview. RESULTS: Fifteen percent (1097/7299) of women with CHD-affected pregnancies (excluding recognized syndromes and single-gene disorders) reported receiving a prenatal CHD diagnosis. Prenatal CHD diagnosis was positively associated with advanced maternal age, family history of CHD, type 1 or type 2 diabetes, twin or higher-order gestation, CHD complexity, and presence of extracardiac defects. Prenatal CHD diagnosis was inversely associated with maternal Hispanic race/ethnicity, prepregnancy overweight or obesity, and preexisting hypertension. Prenatal CHD diagnosis varied by time to NBDPS interview and NBDPS study site. CONCLUSIONS: Further work is warranted to identify reasons for the observed variability in maternal reports of prenatal CHD diagnosis and the extent to which differences in health literacy or health system factors such as access to specialized prenatal care and fetal echocardiography may account for such variability. PMID- 24222435 TI - Genetic mapping of a 7R Al tolerance QTL in triticale (x Triticosecale Wittmack). AB - Triticale (x Triticosecale Wittmack) is a relatively new cereal crop. In Poland, triticale is grown on 12 % of arable land ( http://www.stat.gov.pl ). There is an increasing interest in its cultivation due to lowered production costs and increased adaptation to adverse environmental conditions. However, it has an insufficient tolerance to the presence of aluminum ions (Al(3+)) in the soil. The number of genes controlling aluminum tolerance in triticale and their chromosomal location is not known. Two F2 mapping biparental populations (MP1 and MP15) segregating for aluminum (Al) tolerance were tested with AFLP, SSR, DArT, and specific PCR markers. Genetic mapping enabled the construction of linkage groups representing chromosomes 7R, 5R and 2B. Obtained linkage groups were common for both mapping populations and mostly included the same markers. Composite interval mapping (CIM) allowed identification of a single QTL that mapped to the 7R chromosome and explained 25 % (MP1) and 36 % (MP15) of phenotypic variation. The B1, B26 and Xscm150 markers were 0.04 cM and 0.02 cM from the maximum of the LOD function in the MP1 and MP15, respectively and were highly associated with aluminum tolerance as indicated by Kruskal-Wallis nonparametric test. Moreover, the molecular markers B1, B26, Xrems1162 and Xscm92, previously associated with the Alt4 locus that encoded an aluminum-activated malate transporter (ScALMT1) that was involved in Al tolerance in rye (Secale cereale) also mapped within QTL. Biochemical analysis of plants represented MP1 and MP15 mapping populations confirmed that the QTL located on 7R chromosome in both mapping populations is responsible for Al tolerance. PMID- 24222436 TI - Development of a fluorescent enzyme-linked DNA aptamer-magnetic bead sandwich assay and portable fluorometer for sensitive and rapid leishmania detection in sandflies. AB - A fluorescent peroxidase-linked DNA aptamer-magnetic bead sandwich assay is described which detects as little as 100 ng of soluble protein extracted from Leishmania major promastigotes with a high molarity chaotropic salt. Lessons learned during development of the assay are described and elucidate the pros and cons of using fluorescent dyes or nanoparticles and quantum dots versus a more consistent peroxidase-linked Amplex Ultra Red (AUR; similar to resazurin) fluorescence version of the assay. While all versions of the assays were highly sensitive, the AUR-based version exhibited lower variability between tests. We hypothesize that the AUR version of this assay is more consistent, especially at low analyte levels, because the fluorescent product of AUR is liberated into bulk solution and readily detectable while fluorophores attached to the reporter aptamer might occasionally be hidden behind magnetic beads near the detection limit. Conversely, fluorophores could be quenched by nearby beads or other proximal fluorophores on the high end of analyte concentration, if packed into a small area after magnetic collection when an enzyme-linked system is not used. A highly portable and rechargeable battery-operated fluorometer with on board computer and color touchscreen is also described which can be used for rapid (<1 h) and sensitive detection of Leishmania promastigote protein extracts (~ 100 ng per sample) in buffer or sandfly homogenates for mapping of L. major parasite geographic distributions in wild sandfly populations. PMID- 24222437 TI - Facile and highly efficient approach for the fabrication of multifunctional silk nanofibers containing hydroxyapatite and silver nanoparticles. AB - In this study, a good combination consisting of electrospun silk fibroin nanofibers incorporated with high-purity hydroxyapatite (HAp) nanoparticles (NPs) and silver NPs is introduced as antimicrobial for tissue engineering applications. The variable pressure field emission scanning electron microscope results confirmed randomly placed nanofibers are produced with highly dispersed HAp and silver NPs in nanofibers after electrospinning. The X-ray diffraction results demonstrated crystalline features of each of the three components used for electrospinning. Moreover, the TEM-EDS analysis confirmed the presence and chemical nature of each component over individual silk nanofiber. The FT-IR analyses was used confirm the different vibration modes caused due to functional groups present in silk fibroin, Hap, and silver NPs. The obtained nanofibers were checked for antimicrobial activity by using two model organisms Escherichia coli and Staphylococcus aureus. Subsequently, the antimicrobial tests have indicated that prepared nanofibers do possess good bactericidal activity. The ability of N,N-dimethylformamide and silk fibroin used to reduce silver nitrate into silver metal was evaluated using MTT assay. The nanofibers were grown in presence of NIH 3T3 fibroblasts, which revealed toxic behavior to fibroblasts at higher concentrations of silver nitrate used in this study. Furthermore, cell attachment studies on nanofibers for 3 and 12 days of incubation time were minutely observed and correlated with the results of MTT assay. The reported results confirmed the high amounts of silver nitrate can lead to toxic effects on viability of fibroblasts and had bad effect in cell attachment. PMID- 24222438 TI - Kinetic resolution of axially chiral 2-amino-1,1'-biaryls by phase-transfer catalyzed N-allylation. PMID- 24222439 TI - WITHDRAWN: Interventions to promote the wearing of hearing protection. PMID- 24222440 TI - Biodegradation assessment of PLA and its nanocomposites. AB - Poly(lactic acid) nanocomposites containing Cloisite 15A, Cloisite 30B, and Dellite 43B were prepared by melt-mixing in a batch mixer and were exposed to UV radiation, temperature, and microorganism in solution and in a compost. Exposed samples, collected along the time, were characterized by several techniques. While the addition of organoclays had a positive effect on thermal stability, the degradation rate of nanocomposites increased when exposed to UV radiation and microorganism. Moreover, the degradation rate depends on the organoclay type. Even though the degradation rate is higher for nanocomposites, Fourier transform infrared spectrometry and gel permeation chromatography results demonstrated that the degradation mechanism is the same. PMID- 24222441 TI - Characterization and phylogeny of Isaria spp. strains (Ascomycota: Hypocreales) using ITS1-5.8S-ITS2 and elongation factor 1-alpha sequences. AB - The elongation factor 1-alpha (EF1-alpha) and the internal transcribed spacer (ITS) regions ITS1 and ITS2 (ITS1-5.8S-ITS2) sequences were used to characterize and to identify Isaria isolates from Argentina, Mexico, and Brazil, as well as to study the phylogenetic relationships among these isolates and other related fungi from the order Hypocreales. The molecular characterization, which was performed by PCR-RFLP of EF1-alpha and ITS1-5.8-ITS2 genes, was useful for resolving representative isolates of Isaria fumosorosea, Isaria farinosa, and Isaria tenuipes and to confirm the taxonomic identity of fungi from Argentina, Mexico, and Brazil. The phylogenetic analyses showed three clades corresponding to three families of Hypocreales. The genus Isaria was confirmed as polyphyletic and in family Cordycipitaceae, Isaria species were related to anamorphic species of Beauveria, Lecanicillium, and Simplicillium and to teleomorphic Cordyceps and Torrubiella. Therefore, EF1-alpha and ITS1-5.8S-ITS2 genes were found to be powerful tools for improving the characterization, identification, and phylogenetic relationship of the Isaria species and other entomopathogenic fungi. PMID- 24222442 TI - Modeling costs and benefits of adolescent weight control as a mechanism for reproductive suppression. AB - The "reproductive suppression hypothesis" states that the strong desire of adolescent girls in our culture to control their weight may reflect the operation of an adaptive mechanism by which ancestral women controlled the timing of their sexual maturation and hence first reproduction, in response to cues about the probable success of reproduction in the current situation. We develop a model based on this hypothesis and explore its behavior and evolutionary and psychological implications across a range of parameter values. We use the process of model development to identify assumptions implicit in the reproductive suppression hypothesis and variables that need to be measured in order to investigate it more fully. In addition, because costs were probably associated with weight control, an important part of this analysis is the specification of situations in which the benefits of adaptive adjustment of the maturation schedule could have outweighed the costs of achieving that adjustment by slowing adolescent weight gain. PMID- 24222444 TI - An evolutionary critique of cultural analysis in sociology. AB - A noteworthy development that has transpired in American sociology in the past quarter century has been the increasingly sophisticated interest in the analysis of human cultural systems. Sadly, however, these analyses reveal that social scientists rarely appreciate the profoundly evolutionary aspects of human culture. The chief purpose of this essay is to address this shortcoming and to offer some tentative suggestions toward its rectification. The essay begins by briefly reviewing recent developments in the analysis of cultural systems, primarily by reference to the influential work of Wuthnow. Second, a common flaw in these approaches is addressed-namely, the absence of any recognition of the value of grounding sociocultural theory in an informed evolutionary framework-and the case is made that this shortcoming is avoidable, even within the context of the intellectual traditions of the social sciences. Third, the evolutionary foundations of human cultural behavior are explored in terms of an analysis of relevant theoretical and empirical developments in the evolutionary neurosciences. Fourth, the value of these insights is illustrated by reference to an evolutionary critique of a recent and thought-provoking contribution to the study of modern political culture-Douglas and Wildavsky's analysis ofRisk and Culture. Finally, the article concludes by emphasizing the value of and the necessity for incorporating evolutionary reasoning into the domain of sociocultural theory. PMID- 24222443 TI - Low birth weight, intrauterine growth-retarded, and pre-term infants : A research strategy. AB - Low birth weight, intrauterine growth retardation, and prematurity are overwhelming risk factors associated with infant mortality and morbidity. The lack of efficacious prenatal screening tests for these three outcomes illuminates the problems inherent in bivariate estimates of association. A biocultural strategy for research is presented, integrating societal and familial levels of analysis with the metabolic, immune, vascular, and neuroendocrine systems of the body. Policy decisions, it is argued, need to be based on this type of biocultural information in order to impact the difficult-to-change problems of low birth weight, intrauterine growth retardation, and prematurity. PMID- 24222446 TI - Linear and nonlinear rheology of dense emulsions across the glass and the jamming regimes. AB - We discuss the linear and nonlinear rheology of concentrated microscale emulsions, amorphous disordered solids composed of repulsive and deformable soft colloidal spheres. Based on recent results from simulation and theory, we derive quantitative predictions for the dependences of the elastic shear modulus and the yield stress on the droplet volume fraction. The remarkable agreement with experiments we observe supports the scenario that the repulsive glass and the jammed state can be clearly identified in the rheology of soft spheres at finite temperature while crossing continuously from a liquid to a highly compressed yet disordered solid. PMID- 24222445 TI - Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling. AB - The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis, and progeny differentiation. During morphogenesis, Wnt signaling is well characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically upregulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production, and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the hair germ and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in reformation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a nonredundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands. PMID- 24222447 TI - Synthesis of 6-alkylated phenanthridine derivatives using photoredox neutral somophilic isocyanide insertion. PMID- 24222448 TI - Social isomers of picolines in a small space. AB - Encapsulation complexes permit the observation of molecules under conditions of limited motion. Inside capsules, molecular encounters are prolonged, prearranged, and protected from the medium, in contrast to the short-lived and random encounters that occur in bulk solution. Herein, the interaction of alpha-, beta-, and gamma-picolines in a cylindrical capsule is described. Two picolines were taken up, and NMR spectra indicated dynamic combinations of various social isomers. The stabilities of the complexes are interpreted through computational methods. The shape of the space in the capsule allowed the alignment of molecules and revealed delicate, atom-to-atom interactions and attractive forces that elude observation in dilute solution. These weak forces were amplified in the isolated small space of the capsule. PMID- 24222449 TI - The quality of periconception medical care in women with diabetes needs improvement. AB - OBJECTIVE: We evaluated the quality of periconception medical care in pregnant women with diabetes and assessed the influence of sociodemographic characteristics. RESEARCH DESIGN AND METHODS: The study was based on retrospective data collection from electronic database on cohort of Israeli women at Clalit Health Services (CHS) with pre-existing diabetes who gave birth in 2008 2011. It included data on A1C and other laboratory test results, prescription fillings, diet and ophthalmology consultations, and sociodemographics extracted from CHS computerized systems. The performance of each of nine recommended measures in the periconception period and a composite quality score was evaluated; the score ranged from 0-8. Multivariate logistic regression was used to examine independent sociodemographic predictors of low-quality overall scores. RESULTS: A total of 166 women gave birth to 180 infants; the performance of the different quality parameters ranged from 81% for A1C and kidney function tests to only 30% for dietary consultation and 41.1% for ophthalmology exam. Forty-nine percent of women had A1C <7.0% (53 mmol/mol). Only 45% took folic acid, whereas 13.9% continued the use of potentially teratogenic drugs in the first trimester. One-third of women were in the low-quality (0-3) overall score. In the multiple logistic regression analysis, the only significant variables to predict lower composite quality scores were multiparity odds ratio of 3.43 (95% CI 1.66-7.10; P = 0.001), Arabian ethnicity 3.76 (1.78-7.92; P = 0.001), and immigrant 3.73 (1.25 11.16; P = 0.018). CONCLUSIONS: The periconception medical care of diabetic women is suboptimal. More intensive and targeted care is needed in order to optimize periconception care of diabetic patients, especially in the high-risk subpopulations. PMID- 24222450 TI - Can proopiomelanocortin methylation be used as an early predictor of metabolic syndrome? AB - OBJECTIVE: The objectives of this study were to compare early predictive marker of the metabolic syndrome with proopiomelanocortin (POMC) methylation status and to determine the association among birth weight, ponderal index, and cord blood methylation status. RESEARCH DESIGN AND METHODS: We collected pregnancy outcome data from pregnant women, cord blood samples at delivery, and blood from children (7-9 years old; n = 90) through a prospective cohort study at Ewha Womans University, MokDong Hospital (Seoul, Korea), from 2003-2005. POMC methylation was assessed by pyrosequencing. We divided subjects into three groups according to cord blood POMC methylation: the low methylation (<10th percentile), mid methylation, and high methylation (>90th percentile) groups. We analyzed the association of POMC methylation status at birth with adiposity and metabolic components using ANCOVA and multiple linear regression analysis. RESULTS: Birth weights (P = 0.01) and ponderal indices (P = 0.01) in the high POMC methylation group were significantly lower than in the mid-POMC methylation group. In terms of metabolic components of childhood, blood triglycerides (57.97, 67.29 vs. 113.89 mg/dL; P = 0.03, 0.01) and insulin (7.10, 7.64 vs. 10.13 MUIU/mL; P = 0.05, 0.02) at childhood were significantly higher in the high POMC methylation group than in the low and mid-POMC methylation group. CONCLUSIONS: High POMC methylation in cord blood was associated with lower birth weight, and children with high POMC methylation in cord blood showed higher triglycerides and higher insulin concentrations in blood. Thus, POMC methylation status in cord blood may be an early predictive marker of future metabolic syndrome. PMID- 24222451 TI - Clinical characteristics of infections in humans due to Staphylococcus epidermidis. AB - Staphylococcus epidermidis is the most common cause of primary bacteremia and infections of indwelling medical devices. The ability to cause disease is linked to its natural niche on human skin and ability to attach and form biofilm on foreign bodies. This review focuses on the S. epidermidis clinical syndromes most commonly encountered by clinicians and future potential treatment modalities. PMID- 24222452 TI - Staphylococcus epidermidis pathogenesis. AB - Staphylococcus epidermidis is the most frequently encountered member of the coagulase-negative staphylococci on human epithelial surfaces. It has emerged as an important nosocomial pathogen, especially in infections of indwelling medical devices. The mechanisms that S. epidermidis uses to survive during infection are in general of a passive nature, reflecting their possible origin in the commensal life of this bacterium. Most importantly, S. epidermidis excels in forming biofilms, sticky agglomerations that inhibit major host defense mechanisms. Furthermore, S. epidermidis produces a series of protective surface polymers and exoenzymes. Moreover, S. epidermidis has the capacity to secrete strongly cytolytic members of the phenol-soluble modulin (PSM) family, but PSMs in S. epidermidis overall appear to participate primarily in biofilm development. Finally, there is evidence for a virulence gene reservoir function of S. epidermidis, as it appears to have transferred important immune evasion and antibiotic resistance factors to Staphylococcus aureus. Conversely, S. epidermidis also has a beneficial role in balancing the microflora on human epithelial surfaces by controlling outgrowth of harmful bacteria such as in particular S. aureus. Recent research yielded detailed insight into key S. epidermidis virulence determinants and their regulation, in particular as far as biofilm formation is concerned, but we still have a serious lack of understanding of the in vivo relevance of many pathogenesis mechanisms and the factors that govern the commensal life of S. epidermidis. PMID- 24222453 TI - Identification of Staphylococcus epidermidis in the clinical microbiology laboratory by molecular methods. AB - Biochemical assays for the phenotypic identification of coagulase-negative staphylococci in the clinical microbiology laboratory have been well described in previous publications (Becker and Von Eiff Manual of Clinical Microbiology, ASM Press, Washington, pp. 308-330, 2011; Kloos and Wolfshohl J Clin Microbiol 16:509 516, 1982). This discussion focuses on identification of Staphylococcus epidermidis through molecular and proteomic methods. Molecular assays have been shown to be more discriminatory between the coagulase-negative staphylococcal species than are phenotypic assays (Zadoks and Watts Vet Microbiol 134:20-28, 2009; Sheraba et al. BMC Res Notes 3:278, 2010; Patteet et al. Eur J Clin Microbiol Infect Dis 31:747-751, 2012). The molecular and proteomic methods that have shown the greatest utilization potential within the clinical laboratory are as follows: PCR amplification and sequencing of discriminatory genes, real-time polymerase chain reaction with species-specific probes in conjunction with a melt curve analysis, fluorescence in situ hybridization, and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. PMID- 24222454 TI - Pulsed field gel electrophoresis of Staphylococcus epidermidis. AB - Pulsed field gel electrophoresis (PFGE) is one of the older methods for the molecular characterization and comparison of microorganisms including bacteria. Nevertheless, PFGE continues to be recognized as the gold standard for molecular typing due to output spanning >90 % of the bacterial genome and standardized protocols and reagents applicable to a wide range of organisms including S. epidermidis. PMID- 24222455 TI - Multilocus sequence typing of Staphylococcus epidermidis. AB - Multilocus sequence typing (MLST) is a genotyping method that is well suited for studying the population genetics and evolution of Staphylococcus epidermidis. The central MLST database for S. epidermidis continues to grow, and new analysis methods for extracting historical information from MLST data continue to be developed. Even in this era of whole-genome sequencing, MLST provides a reference genotyping method, and the central MLST database provides a unique catalog of genetic variants. PMID- 24222456 TI - Growth and preparation of Staphylococcus epidermidis for NMR metabolomic analysis. AB - The "omics" era began with transcriptomics and this progressed into proteomics. While useful, these approaches provide only circumstantial information about carbon flow, metabolic status, redox poise, etc. To more directly address these metabolic concerns, researchers have turned to the emerging field of metabolomics. In our laboratories, we frequently use NMR metabolomics to acquire a snapshot of bacterial metabolomes during stressful or transition events. Irrespective of the "omics" method of choice, the experimental outcome depends on the proper cultivation and preparation of bacterial samples. In addition, the integration of these large datasets requires that these cultivation conditions be clearly defined. PMID- 24222457 TI - The isolation and analysis of phenol-soluble modulins of Staphylococcus epidermidis. AB - Phenol-soluble modulins (PSMs) are multifunctional peptide toxins produced by many staphylococcal strains. PSMs have received much recent attention, owing to multiple reports underscoring their importance for staphylococcal pathogenesis. Members of the PSM family may be strongly cytolytic to neutrophils and other cell types; promote inflammatory, receptor-mediated responses in several human cell types; and contribute to biofilm structuring and detachment. Here we describe biochemical methods to isolate, purify, and quantitatively analyze Staphylococcus epidermidis PSMs. PMID- 24222458 TI - Genetic manipulation of staphylococci. AB - The ability to genetically manipulate bacteria is essential to understanding gene/protein function in these organisms. While basic cloning has become routine in molecular biology, many still view the ability to make directed mutations as a daunting or intimidating task. To aid the staphylococcal research community, the goal of this treatise is to describe the method of allelic exchange using temperature-sensitive plasmids that we have used to successfully produce a variety of mutations including single nucleotide changes in the Staphylococcus aureus chromosome. In addition, this chapter provides extensive summaries to aid in the construction of mutations, complementation plasmids, as well as transcription and translation reporters. PMID- 24222459 TI - Isolation of chromosomal and plasmid DNA from Staphylococcus epidermidis. AB - The following describes noncommercial methods for the purification of genomic and plasmid DNA from S. epidermidis. These include both large-scale, high molecular weight and quick, small-scale chromosomal DNA extractions, and also a standard alkaline lysis method of plasmid preparation. PMID- 24222460 TI - Isolation of Staphylococcus sp. RNA. AB - Isolation of RNA (ribonucleic acid) is a valuable technique to study gene regulation and functional RNAs. It is important to obtain pure samples of RNA for downstream applications, while avoiding the negative effects of ribonucleases (RNases). Here we describe several methods of extracting RNA, with an emphasis on Staphylococcus RNA isolation, and measures that must be taken to ensure high quality, high-yield RNA. PMID- 24222461 TI - Use of electroporation and conjugative mobilization for genetic manipulation of Staphylococcus epidermidis. AB - To perform mechanistic studies on the biology of bacteria including metabolism, physiology, and pathogenesis, it is essential to possess the tools required for genetic manipulation. Introduction of plasmid DNA into Staphylococcus epidermidis for subsequent genetic manipulation, including allelic replacement and complementation experiments, is typically performed by either electroporation or conjugative mobilization. Herein, standard protocols and tips for the transfer of plasmid DNA to S. epidermidis by these two methods are provided. PMID- 24222462 TI - Methods to generate a sequence-defined transposon mutant library in Staphylococcus epidermidis strain 1457. AB - Transposon mutant libraries are valuable resources to investigators studying bacterial species, including Staphylococcus epidermidis, which are difficult to genetically manipulate. Although sequence-defined transposon mutant libraries have been constructed in Staphylococcus aureus, no such library exists for S. epidermidis. Nevertheless, the study of Tn917-mediated mutations has been paramount in discovering unique aspects of S. epidermidis biology including initial adherence and accumulation during biofilm formation. Herein, we describe modifications to the methodology first described by Bae et al. to utilize the mariner-based transposon bursa aurealis to generate mutants in S. epidermidis strain 1457. PMID- 24222463 TI - Examination of Staphylococcus epidermidis biofilms using flow-cell technology. AB - A common in vitro method to study Staphylococcus epidermidis biofilm development is to allow the bacteria to attach and grow on a solid surface in the presence of a continuous flow of nutrients. Under these conditions, the bacteria progress through a series of developmental steps, ultimately forming a multicellular structure containing differentiated cell populations. The observation of the biofilm at various time-points throughout this process provides a glimpse of the temporal changes that occur. Furthermore, use of metabolic stains and fluorescent reporters provides insight into the physiologic and transcriptional changes that occur within a developing biofilm. Currently, there are multiple systems available to assess biofilm development, each with advantages and disadvantages depending on the questions being asked. In this chapter, we describe the use of two separate flow-cell systems used to evaluate the developmental characteristics of staphylococcal biofilms: the FC270 flow-cell system from BioSurface Technologies, Corp. and the BioFlux1000 microfluidic flow-cell system from Fluxion Bioscience, Inc. PMID- 24222464 TI - Rapid quantitative and qualitative analysis of biofilm production by Staphylococcus epidermidis under static growth conditions. AB - Rapid screening of biofilm forming capacity by Staphylococcus epidermidis is possible using in vitro assays with 96-well plates. This method first developed by Christensen et al. in 1985 is fast and does not require specialized instruments. Thus, laboratories with standard microbiology infrastructure and a 96-well plate reader can easily use this technique to generate data on the biofilm phenotypes of multiple S. epidermidis strains and clinical isolates. Furthermore, this method can be adapted to gain insights into biofilm regulation and the characteristics of biofilms produced by different S. epidermidis isolates. Although this assay is extremely useful for showing whether individual strains are biofilm-positive or biofilm-negative and distinguishing between form weak, moderate or strong biofilm, it is important to acknowledge that the absolute levels of biofilm produced by an individual strain can vary significantly between experiments meaning that strict adherence to the protocol used is of paramount importance. Furthermore, measuring biofilm under static conditions does not generally reflect in vivo conditions in which bacteria are often subjected to shear stresses under flow conditions. Hence, the biofilm characteristics of some strains are dramatically different under flow and static conditions. Nevertheless, rapid measurement of biofilm production under static conditions is a useful tool in the analysis of the S. epidermidis biofilm phenotype. PMID- 24222465 TI - Bacteriophage Transduction in Staphylococcus epidermidis. AB - The genetic manipulation of Staphylococcus epidermidis for molecular experimentation has long been an area of difficulty. Many of the traditional laboratory techniques for strain construction are laborious and hampered by poor efficiency. The ability to move chromosomal genetic markers and plasmids using bacteriophage transduction has greatly increased the speed and ease of S. epidermidis studies. These molecular genetic advances have advanced the S. epidermidis research field beyond a select few genetically tractable strains and facilitated investigations of clinically relevant isolates. PMID- 24222466 TI - Mouse model of post-arthroplasty Staphylococcus epidermidis joint infection. AB - Animal models are invaluable tools for translational research, allowing investigators to recapitulate observed clinical scenarios within the laboratory that share attributes with human disease. Here, we describe a mouse model of post arthroplasty Staphylococcus epidermidis joint infection which mimics human disease and may be utilized to explore the complex series of events during staphylococcal implant-associated infections by identifying key immunological, bacterial, and/or therapeutic mechanisms relevant to these persistent infections. PMID- 24222467 TI - A mouse model of Staphylococcus catheter-associated biofilm infection. AB - Biofilms are adherent communities of bacteria contained within a complex matrix. Staphylococcal species are frequent etiological agents of device-associated biofilm infections in humans that are highly recalcitrant to antimicrobial therapy and alter host immune responses to facilitate bacterial persistence. Here we describe a mouse model of catheter-associated biofilm infection, which can be utilized to investigate the importance of various staphylococcal determinants on disease progression as well as the host immune response to staphylococcal biofilms. PMID- 24222468 TI - Generation of a central nervous system catheter-associated infection in mice with Staphylococcus epidermidis. AB - Animal models are valuable tools for investigating the in vivo pathogenesis of Staphylococcus epidermidis infections. Here, we present the procedure for generating a central nervous system catheter-associated infection in a mouse, to model the central nervous system shunt infections that frequently complicate the treatment of hydrocephalus in humans. This model uses stereotactic guidance to place silicone catheters, pre-coated with S. epidermidis, into the lateral ventricles of mice. This results in a catheter-associated infection in the brain, with concomitant illness and inflammation. This animal model is a valuable tool for evaluating the pathogenesis of bacterial infection in the central nervous system, the immune response to these infections and potential treatment options. PMID- 24222469 TI - Rat jugular catheter model of biofilm-mediated infection. AB - Staphylococcus epidermidis is now recognized as the primary cause of nosocomial catheter-mediated infections. Bacteria may be introduced exogenously via contamination of the catheter hub or insertion site and endogenously from sepsis. The in vivo model described in this chapter examines the infection resulting from hematogenous seeding of jugular vein catheters. PMID- 24222470 TI - Indigenously produced polyhydroxyalkanoate based co-polymer as cellular supportive biomaterial. AB - The focus of this study was to evaluate the growth of the cells on a scaffold based on novel polyhydroxyalkanoate (PHA) (Polyhydroxy propionate copoly hydroxy ocatadecanoate copolymer), derived from a mutant strain of Pseudomonas sp. Naive PHA was also blended with several biodegradable polymeric materials (PEG, PLA, and MMT) to improve the scaffold properties. Protein adsorption study was done to evaluate the capability of scaffolds for cellular interaction. PHA:PEG blended scaffold showed better adsorption than others. 3T3 fibroblast cultures on various polymers were equally viable when compared with control culture except for the blend PHA:MMT by CCK 8 kit. MTT assay, performed with the continuous cultures HeLa, HEp-2, Vero, and McCoy on the polymer blends, supported the above finding. Among the blends PHA:PEG showed increased viability and was selected for further studies. Cell proliferation assay with colorimetric BrdU ELISA kit showed increase in cell proliferation over the matrix PHA:PEG than that of control. There were no observable morphological changes of continuous cells grown over matrix PHA:PEG when observed by phase contrast microscopy. HEp-2 cells were enclosed within the matrix when analyzed by SEM. The current study states that the scaffold prepared by using the indigenous PHA in combination with PEG supports cell growth better than the conventional plastic surface. PHA:PEG would be a promising material for tissue engineering. PMID- 24222471 TI - Sexual dimorphism in the size and shape of the os coxae and the effects of microevolutionary processes. AB - Sexual dimorphism in the human pelvis has been studied widely for forensic purposes, but it is still unclear to what extent it varies among human populations. There is evidence that microevolutionary processes, both neutral (i.e., population history) and selective (e.g., thermoregulatory adaptation and size-related obstetrical constraints) contribute to explain pelvic variation among populations, but the extent to which these factors affect pelvic sexual dimorphism is unknown. In this study, I analyze sexual dimorphism of the os coxae in 20 globally distributed human populations, using 3D morphometric data to separate the size and shape components of sexual differences. After evaluating population differences in the degree and pattern of sexual dimorphism, I test for the effect of population history, climate, and body size in shaping global diversity. The results show that size and shape dimorphism follow different patterns. Coxal size dimorphism is generally quite consistent through populations, with males bigger than females, but it appears to be reduced in small-bodied populations, possibly in relation to obstetrically-related selective pressures for a spacious birth canal. Beyond a general species-wide pattern of shape dimorphism, commonly used for forensic sex determination, other aspects of sexual differences in coxal shape vary among human populations, reflecting the effects of neutral demographic processes and climatic adaptation. PMID- 24222472 TI - Hypothalamic food intake regulation in a cancer-cachectic mouse model. AB - BACKGROUND: Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore, studying changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite-regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. METHODS: C26-colon adenocarcinoma cells were subcutaneously inoculated in 6 weeks old male CDF1 mice. Body weight and food intake were measured three times a week. On day 20, hypothalamus was dissected and used for transcriptomics using Affymetrix chips. RESULTS: Food intake increased significantly in cachectic tumour-bearing mice (TB), synchronously to the loss of body weight. Hypothalamic gene expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. CONCLUSIONS: Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Further research has to reveal whether targeting these systems will be a good strategy to avoid the development of cancer-induced eating disorders. PMID- 24222473 TI - Simultaneous analysis of polygala acid, senegenin and 3,6'-disinapoylsucrose in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study after oral administration. AB - A rapid and specific LC-MS/MS method has been developed for the simultaneous analysis of polygala acid, senegenin and 3,6'-disinapoylsucrose (DSS) in rat plasma. The method was applied to the pharmacokinetics studies of polygala acid, senegenin and DSS. The analysis was carried out on an Agilent Eclipse plus C18 reversed-phase column (100 * 4.6 mm, 3.5 um) by gradient elution with methanol and ammonia (0.01%, v/v). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polygala acid and DSS ranging from 2.5 to 2000 ng/mL, and senegenin ranging from 5 to 2000 ng/mL. The intra- and inter-day precisions (relative standard deviation) were <11.34 and 8.99%. The extraction recovery ranged from 70.89 +/- 4.60 to 88.49 +/- 3.26%, and that for the IS was 77.23 +/- 3.68%. Stability studies showed that polygala acid, senegenin and DSS are stable during the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of polygala acid, senegenin and DSS. PMID- 24222474 TI - Health literacy: impact on the health of HIV-infected individuals. AB - Health literacy is known to affect vulnerable communities such as persons living with HIV/AIDS. The purpose of this review was to provide a current summary of research on the impact of health literacy on the health of persons living with HIV/AIDS and to address future areas of need. Contemporary studies focused on expanding the reach of health literacy in HIV/AIDS to retention in HIV care, use of technology for assessing and intervening to improve health literacy, and health literacy across the globe, for example. A number of studies did not find health literacy to explain health behaviors whereas other studies supported such a relationship. Future issues relevant to health literacy in HIV/AIDS include the aging of the HIV population and associated comorbidities, studies to understand the role of health literacy in specific populations affected by HIV/AIDS, and the continued need to refine the definition and measurement of health literacy. PMID- 24222475 TI - Case management interventions for HIV-infected individuals. AB - Engagement of HIV-positive persons into care and achieving optimal antiretroviral treatment outcomes is a fundamental HIV prevention strategy. Case management model was recommended as a beneficial model of care for patients with a new HIV diagnosis, focusing on individuals with unmet needs, and linking them with the coordinated health and social services to achieve desired outcomes. HIV case management is population-driven and programs are designed to respond to the unique needs of the client population they serve, such as substance users, homeless, youth, and prison inmates. This view found 28 studies addressing effectiveness and impacts of case management intervention for people living with or at risk of HIV/AIDS. Effectiveness of case management intervention was categorized as follows: decreased mortality and improve health outcomes, linkage to and retention in care, decreased unmet needs, and reducing risky behaviors. PMID- 24222476 TI - Flory theory for polymers. AB - We review various simple analytical theories for homopolymers within a unified framework. The common guideline of our approach is the Flory theory, and its various avatars, with the attempt at being reasonably self-contained. We expect this review to be useful as an introduction to the topic at the graduate student level. PMID- 24222477 TI - Cost effectiveness of medication adherence-enhancing interventions: a systematic review of trial-based economic evaluations. AB - BACKGROUND: In light of the pressure to reduce unnecessary healthcare expenditure in the current economic climate, a systematic review that assesses evidence of cost effectiveness of adherence-enhancing interventions would be timely. OBJECTIVE: Our objective was to examine the cost effectiveness of adherence enhancing interventions compared with care as usual in randomised controlled trials, and to assess the methodological quality of economic evaluations. METHODS: MEDLINE, PsycInfo, EconLit and the Centre for Reviews and Dissemination databases were searched for randomised controlled trials reporting full economic evaluations of adherence-enhancing interventions (published up to June 2013). Information was collected on study characteristics, cost effectiveness of treatment alternatives, and methodological quality. RESULTS: A total of 14 randomised controlled trials were included. The quality of economic evaluations and the risk of bias varied considerably between trials. Four studies showed incremental cost-effectiveness ratios (ICERs) below the willingness-to-pay threshold. Few studies seemed to evaluate interventions that successfully changed adherence. CONCLUSIONS: Only 14 randomised controlled trials examined the cost effectiveness of adherence interventions. Despite that some studies showe favourable ICERs, the overall quality of studies was modest and the economic perspectives applied were frequently narrow. To demonstrate that adherence interventions can be cost effective, we recommend that proven-effective adherence programmes are subjected to comprehensive economic evaluations. PMID- 24222478 TI - Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide. AB - Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA-NMU displayed long-lasting, potent anorectic, and glucose-normalizing activity. When compared side by side with a previously described PEG conjugate, HSA-NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU-based therapeutics are promising candidates for the treatment of obesity and diabetes. PMID- 24222479 TI - Outstanding catalytic activity of ultra-pure platinum nanoparticles. AB - Small (4 nm) nanoparticles with a narrow size distribution, exceptional surface purity, and increased surface order, which exhibits itself as an increased presence of basal crystallographic planes, can be obtained without the use of any surfactant. These nanoparticles can be used in many applications in an as received state and are threefold more active towards a model catalytic reaction (oxidation of ethylene glycol). Furthermore, the superior properties of this material are interesting not only due to the increase in their intrinsic catalytic activity, but also due to the exceptional surface purity itself. The nanoparticles can be used directly (i.e., as-received, without any cleaning steps) in biomedical applications (i.e., as more efficient drug carriers due to an increased number of adsorption sites) and in energy-harvesting/data-storage devices. PMID- 24222480 TI - Perinatal outcomes after bariatric surgery: nationwide population based matched cohort study. AB - OBJECTIVE: To compare perinatal outcomes in births of women with versus without a history of bariatric surgery. DESIGN: Population based matched cohort study. SETTING: Swedish national health service. PARTICIPANTS: 1,742,702 singleton births identified in the Swedish medical birth register between 1992 and 2009. For each birth to a mother with a history of bariatric surgery (n=2562), up to five control births were matched by maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, educational level, and year of delivery. Secondary control cohorts, including women eligible for bariatric surgery (body mass index >= 35 or >= 40), were matched for the same factors except body mass index. History of maternal bariatric surgery was ascertained through the Swedish national patient register from 1980 to 2009. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks), small for gestational age birth, large for gestational age birth, stillbirth (>= 28 weeks), and neonatal death (0-27 days). RESULTS: Post-surgery births were more often preterm than in matched controls (9.7% (243/2511) v 6.1% (750/12,379); odds ratio 1.7, 95% confidence interval 1.4 to 2.0; P<0.001). Body mass index seemed to be an effect modifier (P=0.01), and the increased risk of preterm birth was only observed in women with a body mass index <35. A history of bariatric surgery was associated with increased risks of both spontaneous (5.2% (130/2511) v 3.6% (441/12,379); odds ratio 1.5, 1.2 to 1.9; P<0.001) and medically indicated preterm birth (4.5% (113/2511) v 2.5% (309/12,379); odds ratio 1.8, 1.4 to 2.3; P<0.001). A history of bariatric surgery was also associated with an increased risk of a small for gestational age birth (5.2% (131/2507) v 3.0% (369/12,338); odds ratio 2.0, 1.5 to 2.5; P<0.001) and lower risk of a large for gestational age birth (4.2% (105/2507) v 7.3% (895/12,338); odds ratio 0.6, 0.4 to 0.7; P<0.001). No differences were detected for stillbirth or neonatal death. The increased risks for preterm and small for gestational age birth, as well as the decreased risk for large for gestational age birth, remained when post-surgery births were compared with births of women eligible for bariatric surgery. CONCLUSION: Women with a history of bariatric surgery were at increased risk of preterm and small for gestational age births and should be regarded as a risk group during pregnancy. PMID- 24222481 TI - Population ageing: the timebomb that isn't? PMID- 24222482 TI - Should influenza vaccination be mandatory for healthcare workers? PMID- 24222483 TI - Three clinical experiences with SNP array results consistent with parental incest: a narrative with lessons learned. AB - Single nucleotide polymorphism microarrays have the ability to reveal parental consanguinity which may or may not be known to healthcare providers. Consanguinity can have significant implications for the health of patients and for individual and family psychosocial well-being. These results often present ethical and legal dilemmas that can have important ramifications. Unexpected consanguinity can be confounding to healthcare professionals who may be unprepared to handle these results or to communicate them to families or other appropriate representatives. There are few published accounts of experiences with consanguinity and SNP arrays. In this paper we discuss three cases where molecular evidence of parental incest was identified by SNP microarray. We hope to further highlight consanguinity as a potential incidental finding, how the cases were handled by the clinical team, and what resources were found to be most helpful. This paper aims to contribute further to professional discourse on incidental findings with genomic technology and how they were addressed clinically. These experiences may provide some guidance on how others can prepare for these findings and help improve practice. As genetic and genomic testing is utilized more by non-genetics providers, we also hope to inform about the importance of engaging with geneticists and genetic counselors when addressing these findings. PMID- 24222484 TI - Frustrated Lewis pairs as molecular receptors: colorimetric and electrochemical detection of nitrous oxide. PMID- 24222485 TI - JCCS: a comprehensive journal for publishing all aspects of cell communication and signaling. PMID- 24222486 TI - False results caused by solvent impurity in tetrahydrofuran for MALDI TOF MS analysis of amines. AB - Tetrahydrofuran (THF) is one of the most frequently used solvents in the MALDI TOF MS analysis of synthetic compounds. However, it should be used with caution because a trace amount of 4-hydroxybutanal (HBA) might be generated and accumulated in THF during storage. Since only a tiny amount of analytes is required in MALDI MS measurements, a trace amount of HBA might have a significant effect on the MS results. It was found that HBA will quickly react with primary and secondary amino compounds, leading to false results about the sample composition with an extra series of ions with additional mass of 70 Da in between. The formation of HBA can be inhibited by butylated hydroxytoluene (BHT) antioxidant. Therefore, when THF is required as the solvent for sample preparation, it is strongly recommended to use a BHT-stabilized one, at least for the analysis of compounds with amino groups. PMID- 24222487 TI - The Staphylococcus aureus SrrAB two-component system promotes resistance to nitrosative stress and hypoxia. AB - Staphylococcus aureus is both a commensal and a pathogen of the human host. Survival in the host environment requires resistance to host-derived nitric oxide (NO.). However, S. aureus lacks the NO.-sensing transcriptional regulator NsrR that is used by many bacteria to sense and respond to NO.. In this study, we show that S. aureus is able to sense and respond to both NO. and hypoxia by means of the SrrAB two-component system (TCS). Analysis of the S. aureus transcriptome during nitrosative stress demonstrates the expression of SrrAB-dependent genes required for cytochrome biosynthesis and assembly (qoxABCD, cydAB, hemABCX), anaerobic metabolism (pflAB, adhE, nrdDG), iron-sulfur cluster repair (scdA), and NO. detoxification (hmp). Targeted mutations in SrrAB-regulated loci show that hmp and qoxABCD are required for NO. resistance, whereas nrdDG is specifically required for anaerobic growth. We also show that SrrAB is required for survival in static biofilms, most likely due to oxygen limitation. Activation by hypoxia, NO., or a qoxABCD quinol oxidase mutation suggests that the SrrAB TCS senses impaired electron flow in the electron transport chain rather than directly interacting with NO. in the manner of NsrR. Nevertheless, like NsrR, SrrAB achieves the physiological goals of selectively expressing hmp in the presence of NO. and minimizing the potential for Fenton chemistry. Activation of the SrrAB regulon allows S. aureus to maintain energy production and essential biosynthetic processes, repair damage, and detoxify NO. in diverse host environments. IMPORTANCE: The Hmp flavohemoglobin is required for nitric oxide resistance and is widely distributed in bacteria. Hmp expression must be tightly regulated, because expression under aerobic conditions in the absence of nitric oxide can exacerbate oxidative stress. In most organisms, hmp expression is controlled by the Fe-S cluster-containing repressor NsrR, but this transcriptional regulator is absent in the human pathogen Staphylococcus aureus. We show here that S. aureus achieves hmp regulation in response to nitric oxide and oxygen limitation by placing it under the control of the SrrAB two-component system, which senses reduced electron flow through the respiratory chain. This provides a striking example of convergent evolution, in which the common physiological goals of responding to nitrosative stress while minimizing Fenton chemistry are achieved by distinct regulatory mechanisms. PMID- 24222488 TI - Overproduction of flotillin influences cell differentiation and shape in Bacillus subtilis. AB - Bacteria organize many membrane-related signaling processes in functional microdomains that are structurally and functionally similar to the lipid rafts of eukaryotic cells. An important structural component of these microdomains is the protein flotillin, which seems to act as a chaperone in recruiting other proteins to lipid rafts to facilitate their interaction. In eukaryotic cells, the occurrence of severe diseases is often observed in combination with an overproduction of flotillin, but a functional link between these two phenomena is yet to be demonstrated. In this work, we used the bacterial model Bacillus subtilis as a tractable system to study the physiological alterations that occur in cells that overproduce flotillin. We discovered that an excess of flotillin altered specific signal transduction pathways that are associated with the membrane microdomains of bacteria. As a consequence of this, we detected significant defects in cell division and cell differentiation. These physiological alterations were in part caused by an unusual stabilization of the raft-associated protease FtsH. This report opens the possibility of using bacteria as a working model to better understand fundamental questions related to the functionality of lipid rafts. IMPORTANCE: The identification of signaling platforms in the membrane of bacteria that are functionally and structurally equivalent to eukaryotic lipid rafts reveals a level of sophistication in signal transduction and membrane organization unexpected in bacteria. It opens new and promising venues to address intricate questions related to the functionality of lipid rafts by using bacteria as a more tractable system. This is the first report that uses bacteria as a working model to investigate a fundamental question that was previously raised while studying the role of eukaryotic lipid rafts. It also provides evidence of the critical role of these signaling platforms in orchestrating diverse physiological processes in prokaryotic cells. PMID- 24222490 TI - Bacteriophages as pathogens and immune modulators? AB - While Shiga toxins (Stx) are key determinants of enterohemorrhagic Escherichia coli (EHEC) pathophysiology in humans, their dissemination to target organs following gastrointestinal EHEC infection is still poorly understood. Most types of Stx target cells with globotriaosylceramide (Gb3) receptors, which are expressed on endothelial cells. According to current theory, Stx is trafficked on the surface of peripheral blood cells, and transfer of toxin from these trafficking cells to endothelial cells results in microvascular damage to target organs, including the kidneys and brain. Inside the cell, Stx inhibits protein synthesis, resulting in cell death. Host "repair" responses can lead to microthrombus formation, erythrocyte damage, and reduced oxygen supply, potentially resulting in organ failure. A recent study [L. V. Bentancor et al., mBio 4(5):e00501-13, 2013, doi:10.1128/mBio.00501-13] indicates that another mechanism for Stx "dissemination" needs to be considered. Bentancor et al. demonstrated that high-pressure injection of a plasmid encoding the "prokaryotic" Stx2 sequence into mice can lead to mortality, with pathology indicative of Stx activity and antibody responses to Stx. While the plasmid levels and injection methodology were extreme, the study indicates that these sequences are potentially taken up into eukaryotic cells, transcribed, and translated, producing active Stx. Stx genes are present on integrated bacteriophage genomes in EHEC, and Stx-encoding phages are released following bacterial lysis in the gastrointestinal tract. We therefore need to consider whether bacteriophage sequences can be expressed in eukaryotic cells, what the wider implications are for our understanding of many "bacterial" diseases, and the possibility of developing novel interventions that target bacteriophages. PMID- 24222489 TI - A retrograde trafficking inhibitor of ricin and Shiga-like toxins inhibits infection of cells by human and monkey polyomaviruses. AB - Polyomaviruses are ubiquitous pathogens that cause severe disease in immunocompromised individuals. JC polyomavirus (JCPyV) is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), whereas BK polyomavirus (BKPyV) causes polyomavirus-induced nephropathy and hemorrhagic cystitis. Vaccines or antiviral therapies targeting these viruses do not exist, and treatments focus on reducing the underlying causes of immunosuppression. We demonstrate that retro-2(cycl), an inhibitor of ricin and Shiga-like toxins (SLTs), inhibits infection by JCPyV, BKPyV, and simian virus 40. Retro-2(cycl) inhibits retrograde transport of polyomaviruses to the endoplasmic reticulum, a step necessary for productive infection. Retro-2(cycl) likely inhibits polyomaviruses in a way similar to its ricin and SLT inhibition, suggesting an overlap in the cellular host factors used by bacterial toxins and polyomaviruses. This work establishes retro-2(cycl) as a potential antiviral therapy that broadly inhibits polyomaviruses and possibly other pathogens that use retrograde trafficking. IMPORTANCE: The human polyomaviruses JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) cause rare but severe diseases in individuals with reduced immune function. During immunosuppression, JCPyV disseminates from the kidney to the central nervous system and destroys oligodendrocytes, resulting in the fatal disease progressive multifocal leukoencephalopathy. Kidney transplant recipients are at increased risk of BKPyV-induced nephropathy, which results in kidney necrosis and loss of the transplanted organ. There are currently no effective therapies for JCPyV and BKPyV. We show that a small molecule named retro-2(cycl) protects cells from infection with JCPyV and BKPyV by inhibiting intracellular viral transport. Retro-2(cycl) treatment reduces viral spreading in already established infections and may therefore be able to control infection in affected patients. Further optimization of retro-2(cycl) may result in the development of an effective antiviral therapy directed toward pathogens that use retrograde trafficking to infect their hosts. PMID- 24222492 TI - An unusual mechanism of isopeptide bond formation attaches the collagenlike glycoprotein BclA to the exosporium of Bacillus anthracis. PMID- 24222491 TI - Genome-wide effects of selenium and translational uncoupling on transcription in the termite gut symbiont Treponema primitia. AB - When prokaryotic cells acquire mutations, encounter translation-inhibiting substances, or experience adverse environmental conditions that limit their ability to synthesize proteins, transcription can become uncoupled from translation. Such uncoupling is known to suppress transcription of protein encoding genes in bacteria. Here we show that the trace element selenium controls transcription of the gene for the selenocysteine-utilizing enzyme formate dehydrogenase (fdhFSec) through a translation-coupled mechanism in the termite gut symbiont Treponema primitia, a member of the bacterial phylum Spirochaetes. We also evaluated changes in genome-wide transcriptional patterns caused by selenium limitation and by generally uncoupling translation from transcription via antibiotic-mediated inhibition of protein synthesis. We observed that inhibiting protein synthesis in T. primitia influences transcriptional patterns in unexpected ways. In addition to suppressing transcription of certain genes, the expected consequence of inhibiting protein synthesis, we found numerous examples in which transcription of genes and operons is truncated far downstream from putative promoters, is unchanged, or is even stimulated overall. These results indicate that gene regulation in bacteria allows for specific post initiation transcriptional responses during periods of limited protein synthesis, which may depend both on translational coupling and on unclassified intrinsic elements of protein-encoding genes. IMPORTANCE: A large body of literature demonstrates that the coupling of transcription and translation is a general and essential method by which bacteria regulate gene expression levels. However, the potential role of noncanonical amino acids in regulating transcriptional output via translational control remains, for the most part, undefined. Furthermore, the genome-wide transcriptional state in response to translational decoupling is not well quantified. The results presented here suggest that the noncanonical amino acid selenocysteine is able to tune transcription of an important metabolic gene via translational coupling. Furthermore, a genome-wide analysis reveals that transcriptional decoupling produces a wide-ranging effect and that this effect is not uniform. These results exemplify how growth conditions that impact translational processivity can rapidly feed back on transcriptional productivity of prespecified groups of genes, providing bacteria with an efficient response to environmental changes. PMID- 24222493 TI - Dietary habits and metabolic control in adolescents and young adults with phenylketonuria: self-imposed protein restriction may be harmful. AB - BACKGROUND: In untreated patients, phenylketonuria (PKU) results in severe encephalopathy with mental retardation. A protein-restricted diet is recommended which can be relaxed in adolescence/adulthood. METHODS: We contacted all 72 adult/adolescent PKU patients who had been treated in our center during early childhood. Some still regularly attended our outpatient clinics, while others were lost for follow-up, giving 51 patients in our study. We asked all patients to complete a dietary protocol as well as a questionnaire on quality of life. Blood and urine were analyzed and body impedance plethysmography and cerebral MRI were performed. RESULTS: 42 % of the patients followed protein restriction supplemented with amino acid mixtures (AAM), others had a vegan diet with (8 %) or without (14 %) AAM; 36 % said they were eating normally and did not need any AAM. However, based on dietary protocols and blood urea levels, protein intake was restricted in this patient group. None of the patients examined had serious nutritional deficits. Phenylalanine levels were higher in patients not taking AAM. MRI of the brain was not different from those following protein restriction and taking AAM. The lesions score and mood correlated best with the cumulative phenylalanine values during the first 10 years of life. CONCLUSION: In summary, 50 % of adult/adolescent patients from our center did not take AAM at the start of our survey although they unknowingly followed self-imposed protein restriction. They had no overt nutritional deficits; however, long-term brain function may be compromised. Our study emphasizes the need for specialized metabolic care in PKU during adulthood. PMID- 24222494 TI - Danon Disease Due to a Novel LAMP2 Microduplication. AB - Danon disease is a rare X-linked disorder comprising hypertrophic cardiomyopathy, skeletal myopathy, intellectual disability, and retinopathy; mutations of the lysosome-associated membrane protein gene LAMP2 are responsible. Most affected persons exhibit "private" point mutations; small locus rearrangements have recently been reported in four cases. Here, we describe the clinical, pathologic, and molecular features of a male proband and his affected mother with Danon disease and a small LAMP2 microduplication. The proband presented at age 12 years with exercise intolerance, hypertrophic cardiomyopathy, and increased creatine kinase. Endomyocardial biopsy findings were nonspecific, showing myocyte hypertrophy and reactive mitochondrial changes. Quadriceps muscle biopsy demonstrated the characteristic autophagic vacuoles with sarcolemma-like features. LAMP2 tissue immunostaining was absent; however, LAMP2 sequencing was normal. Deletion/duplication testing by multiplex ligation-dependent probe amplification (MLPA) assay revealed a 1.5kb microduplication containing LAMP2 exons 4 and 5. RT-PCR studies were consistent with the inclusion of these two duplicated exons in the final spliced transcript, resulting in a frameshift. The proband's mother, who had died following cardiac transplantation due to suspected myocarditis at age 35, was reviewed and was shown to be affected upon immunostaining of banked myocardial tissue. This case constitutes the second report of a pathogenic microduplication in Danon disease, and illustrates a number of potential diagnostic pitfalls. Firstly, given the imperfect sensitivity of LAMP2 sequencing, tissue immunostaining and/or MLPA should be considered as a diagnostic adjunct in the workup for this disorder. Secondly, the pathological findings in myocardium may be falsely indicative of relatively common conditions such as myocarditis. PMID- 24222495 TI - Selection of a thermotolerant Kluyveromyces marxianus strain with potential application for cellulosic ethanol production by simultaneous saccharification and fermentation. AB - The development of technologies for cellulosic ethanol production by simultaneous saccharification and fermentation (SSF) depends on the use of microorganisms with high fermentative rates and thermotolerance. In this study, the ability of five Kluyveromyces marxianus strains to produce ethanol from glucose at 45 degrees C was investigated. The highest fermentative parameters were observed with K. marxianus NRRL Y-6860, which was then further studied. An initial evaluation of the oxygen supply on ethanol production by the selected yeast and a comparison of SSF process from acid pretreated rice straw between K. marxianus NRRL Y-6860 and Saccharomyces cerevisiae at 30 and 45 degrees C were carried out. Under the lowest evaluated conditions of aeration and agitation, K. marxianus NRRL Y-6860 produced 21.5 g/L ethanol from 51.3 g/L glucose corresponding to YP/S of 0.44 g/g and QP of 3.63 g/L h. In the SSF experiments, K. marxianus NRRL Y-6860 was more efficient than S. cerevisiae at both evaluated temperatures (30 and 45 degrees C), attained at the highest temperature an ethanol yield of 0.24 g/g and productivity of 1.44 g/L h. PMID- 24222496 TI - Comparison of the catalytic activities of three isozymes of carnitine palmitoyltransferase 1 expressed in COS7 cells. AB - The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine, and three isozymes of it, 1a, 1b, and 1c, have been identified. Interestingly, the 1c isozyme was reported to show no enzymatic activity, but it was not clearly demonstrated whether this inactivity was due to its dysfunction or due to its poor expression. In the present study, we (a) expressed individual CPT1 isozymes in COS7 cells, (b) evaluated quantitatively their expression levels by Western blotting using the three bacterially expressed CPT1 isozymes as standards, and (c) evaluated their catalytic activities. With these experiments, we successfully demonstrated that the absence of the enzymatic activity of the 1c isozyme was due to its dysfunction. In addition, experiments on the preparation of standard CPT1 isozymes revealed that the 1c isozyme did not show the standard relationship between migration in an SDS-PAGE gel and molecular size. We further tried to determine why the 1c isozyme was inert by preparing chimeric CPT1 between 1a and 1c, but no clear conclusion could be drawn because one of the chimeric CPT1s was not sufficiently expressed. PMID- 24222497 TI - Application of enzyme for improvement of Acacia APMP pulping and refining of mixed pulp for printing papermaking in Vietnam. AB - This study assesses the influence of commercial enzyme (FibreZyme LBR) treatment applied to APMP pulp and to the mixture of 55% Acacia CTMP75 pulp, 30% soft-wood bleached chemical pulp (LBKP 90 from Chile) and 15% hard-wood bleached chemical pulp (NPKP 90 from Indonesia). The treatment was conducted at different temperatures, reaction times and enzyme dosages. The APMP and mixed pulp treated with the enzyme showed a significant decrease of refining time to achieve the same refining degree (Schopper-Riegler freeness, degrees SR) and better mechanical-physical properties due to the development of fibrillation. The fibre morphology difference between before and after treatment was revealed by the microscopic observations performed by a scanning electron microscope (SEM). The SEM analysis showed that the surface of the enzyme-treated fibre had some swelling and fibrillar phenomenon that lead to strong paper properties such as tear index, tensile index and burst index. PMID- 24222498 TI - Improved polysaccharide production in submerged culture of Ganoderma lucidum by the addition of coixenolide. AB - Polysaccharides from Ganoderma lucidum have various bioactivities and have been widely used as nutraceuticals and functional foods. Coixenolide was added into the media to enhance the production of mycelia biomass and polysaccharides in the submerged culture of G. lucidum in this work. The results showed that when a level of 0.2% coixenolide was added at day 1, the biomass, exopolysaccharide, and intracellular polysaccharide reached 5.224, 0.222, and 0.399 g l(-1), respectively, which were 1.39-fold, 2.58-fold, and 2.24-fold compared to that of control. Analysis of the fermentation kinetics of G. lucidum suggested that glucose concentration in the coixenolide-added group decreased more quickly as compared to the control group from days 3 to 9 of the fermentation process, and the polysaccharides biosynthesis were promoted at the same culture period. However, the culture pH profile was not affected by the addition of coixenolide. Enzyme activities analysis indicated that coixenolide affected the synthesis level of phosphoglucose isomerase and alpha-phosphoglucomutase. PMID- 24222499 TI - Evidence that pulsed electric field treatment enhances the cell wall porosity of yeast cells. AB - The application of rectangular electric pulses, with 0.1-2 ms duration and field intensity of 2.5-4.5 kV/cm, to yeast suspension mediates liberation of cytoplasmic proteins without cell lysis. The aim of this study was to evaluate the effect of pulsed electric field with similar parameters on cell wall porosity of different yeast species. We found that electrically treated cells become more susceptible to lyticase digestion. In dependence on the strain and the electrical conditions, cell lysis was obtained at 2-8 times lower enzyme concentration in comparison with control untreated cells. The increase of the maximal lysis rate was between two and nine times. Furthermore, when applied at low concentration (1 U/ml), the lyticase enhanced the rate of protein liberation from electropermeabilized cells without provoking cell lysis. Significant differences in the cell surface of control and electrically treated cells were revealed by scanning electron microscopy. Data presented in this study allow us to conclude that electric field pulses provoke not only plasma membrane permeabilization, but also changes in the cell wall structure, leading to increased wall porosity. PMID- 24222500 TI - Cultivation of Chlorella protothecoides with urban wastewater in continuous photobioreactor: biomass productivity and nutrient removal. AB - The capability to grow microalgae in nonsterilized wastewater is essential for an application of this technology in an actual industrial process. Batch experiments were carried out with the species in nonsterilized urban wastewater from local treatment plants to measure both the algal growth and the nutrient consumption. Chlorella protothecoides showed a high specific growth rate (about 1 day(-1)), and no effects of bacterial contamination were observed. Then, this microalgae was grown in a continuous photobioreactor with CO2-air aeration in order to verify the feasibility of an integrated process of the removal of nutrient from real wastewaters. Different residence times were tested, and biomass productivity and nutrients removal were measured. A maximum of microalgae productivity was found at around 0.8 day of residence time in agreement with theoretical expectation in the case of light-limited cultures. In addition, N-NH4 and P-PO4 removal rates were determined in order to model the kinetic of nutrients uptake. Results from batch and continuous experiments were used to propose an integrated process scheme of wastewater treatment at industrial scale including a section with C. protothecoides. PMID- 24222501 TI - In vitro propagation and assessment of the genetic fidelity of Musa acuminata (AAA) cv. Vaibalhla derived from immature male flowers. AB - An efficient in vitro propagation method has been developed for the first time for Musa acuminata (AAA) cv. Vaibalhla, an economically important banana cultivar of Mizoram, India. Immature male flowers were used as explants. Murashige and Skoog's (MS) medium supplemented with plant growth regulators (PGRs) were used for the regeneration process. Out of different PGR combinations, MS medium supplemented with 2 mg L(-1) 6-benzylaminopurine (BAP) + 0.5 mg L(-1) alpha naphthalene acetic acid (NAA) was optimal for production of white bud-like structures (WBLS). On this medium, explants produced the highest number of buds per explant (4.30). The highest percentage (77.77) and number (3.51) of shoot formation from each explants was observed in MS medium supplemented with 2 mg L( 1) kinetin + 0.5 mg L(-1) NAA. While MS medium supplemented with a combination of 2 mg L(-1) BAP + 0.5 mg L(-1) NAA showed the maximum shoot length (14.44 cm). Rooting efficiency of the shoots was highest in the MS basal medium without any PGRs. The plantlets were hardened successfully in the greenhouse with 96% survival rate. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were employed to assess the genetic stability of in vitro regenerated plantlets of M. acuminata (AAA) cv. Vaibalhla. Eight RAPD and 8 ISSR primers were successfully used for the analysis from the 40 RAPD and 30 ISSR primers screened initially. The amplified products were monomorphic across all the regenerated plants and were similar to the mother plant. The present standardised protocol will find application in mass production, conservation and genetic transformation studies of this commercially important banana. PMID- 24222502 TI - Direct electron transfer at a glucose oxidase-chitosan-modified Vulcan carbon paste electrode for electrochemical biosensing of glucose. AB - This article describes the investigation of direct electron transfer (DET) between glucose oxidase (GOD) and the electrode materials in an enzyme-catalyzed reaction for the development of improved bioelectrocatalytic system. The GOD pedestal electrochemical reaction takes place by means of DET in a tailored Vulcan carbon paste electrode surfaces with GOD and chitosan (CS), allowing efficient electron transfer between the electrode and enzyme. The key understanding of the stability, biocatalytic activity, selectivity, and redox properties of these enzyme-based glucose biosensors is studied without using any reagents, and the properties are characterized using electrochemical techniques like cyclic voltammogram, amperometry, and electrochemical impedance spectroscopy. Furthermore, the interaction between the enzyme and the electrode surface is studied using ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy. The present glucose biosensor exhibited better linearity, limit of detection (LOD = 0.37 +/- 0.02 mol/L) and a Michaelis-Menten constant of 0.40 +/- 0.01 mol/L. The proposed enzyme electrode exhibited excellent sensitivity, selectivity, reproducibility, and stability. This provides a simple "reagent-less" approach and efficient platform for the direct electrochemistry of GOD and developing novel bioelectrocatalytic systems. PMID- 24222503 TI - Hydrolyzabilities of different corn stover fractions after aqueous ammonia pretreatment. AB - The effect of aqueous ammonia pretreatment on the hydrolysis of different corn stover fractions (rind, husk, leaf, and pith) by xylanase (XYL) with cellulases (CELs) was evaluated. The aqueous ammonia pretreatment had excellent delignification ability (above 66%) for different corn stover fractions. The corn rind exhibited the lowest susceptibility to aqueous ammonia pretreatment. The pretreated rind showed the lowest hydrolyzability by CEL and XYL, which was supported by a high content of crystalline cellulose in the hydrolyzed residues of rind, as confirmed by X-ray diffraction (XRD). With the addition of 1 mg XYL/g dry matter, a high glucose yield (above 90%) could be obtained from the pretreated rind by CEL. The results revealed that a high hydrolyzate yield of corn rind after aqueous ammonia pretreatment could be obtained with 1 mg xylanase/g dry matter, showing that aqueous ammonia pretreatment and xylanase addition to cellulases have great potential for the efficient hydrolysis of corn stover without previous fractionation. PMID- 24222504 TI - Inflammatory and microenvironmental factors involved in breast cancer progression. AB - The primary reason for the high mortality rate of breast cancer is metastasis, which can result in a poor survival rate. The tumor environment is important for promotion and invasion of cancer cells. Recent studies have shown that inflammation is associated with breast cancer. Therefore, it is important to investigate the role of the inflammatory and microenvironment in breast cancer progression and metastasis. The present review summarizes some of the markers for inflammation and breast cancer invasion, which may aid in the design of an appropriate therapy for metastatic breast cancer. The following four inflammatory markers are discussed in this review: (1) Tumor associated macrophages (TAMs); (2) Matrix metalloproteinases (MMPs); (3) Sphingosine 1-phosphate (S1P); (4) C reactive protein (CRP). TAMs are commonly found in breast cancer patients, and high infiltration is positively correlated with poor prognosis and low survival rate. MMPs are well-known for their roles in the degradation of ECM components when cancer cells invade and migrate. MMPs are also associated with inflammation through recruitment of a variety of stromal cells such as fibroblasts and leukocytes. S1P is an inflammatory lipid and is involved in various cellular processes such as proliferation, survival, and migration. Recent studies indicate that S1P participates in breast cancer invasion in various ways. CRP is used clinically to indicate the outcome of cancer patients as well as acute inflammatory status. This review summarizes the current understanding on the role of S1P in CRP expression which promotes the breast epithelial cell invasion, suggesting a specific mechanism linking inflammation and breast cancer. The present review might be useful for understanding the relationship between inflammation and breast cancer for the development of pharmacological interventions that may control the primary molecules involved in the breast cancer microenvironment. PMID- 24222505 TI - Nonviral delivery for reprogramming to pluripotency and differentiation. AB - Nonviral delivery is a promising strategy for cellular reprogramming to produce desired cell types from undifferentiated stem cells or terminally differentiated somatic cells. Nonviral delivery of genes (DNA, RNA), proteins, or peptides has the potential to reprogram somatic cells to pluripotent stem cells or other lineage cells, and to promote the differentiation of stem cells to specific lineages. Various delivery carriers (cationic polymers, lipids, scaffolds, transposons, cell-penetrating peptides), cargos (episomal plasmids, minicircle DNA, small interfering RNAs, microRNAs, proteins, peptides), and method (electroporation) have been reported. In this article, we review recent advances in nonviral delivery approaches for reprogramming cells to pluripotency or lineage specification. PMID- 24222508 TI - The relation between social support and smoking cessation: revisiting an established measure to improve prediction. AB - BACKGROUND: Although social support is an integral element in smoking cessation, the literature presents mixed findings regarding the type(s) of social support that are most helpful. The Partner Interaction Questionnaire (PIQ) is commonly used to measure social support in this context. PURPOSE: We explored the possibility that more nuanced distinctions between items on the PIQ than what is customarily used could improve the prediction of cessation. METHODS: Baseline PIQ responses of smokers enrolled in a cessation program was submitted to an exploratory factor analysis. Emergent factors were used to predict cessation at several time points. RESULTS: Four factors emerged, which differed from the two subscales that are typically used. The four-factor version predicted cessation; the two-factor version did not. CONCLUSIONS: Identifying the types of social support that predict smoking cessation depend on our ability to measure social support. More nuanced measures will likely clarify the role of social support in cessation. PMID- 24222509 TI - Contemplating genetic feedback regarding lung cancer susceptibility. AB - BACKGROUND AND PURPOSE: We examined three theoretical models (self-enhancement theory, consistency theory, and a combined model) for understanding how expectations and test result favorability influence smokers' desire for a retest following hypothetical genetic test results. METHOD: College smokers (N = 128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk). Participants then reported whether they would get retested if they received favorable GSTM1 results versus unfavorable GSTM1 results. RESULTS: Participants were most likely to want a retest, suggesting rejection of the results, if they expected favorable news yet received unfavorable news. CONCLUSION: The findings supported the combined model such that smokers expressed greatest interest in a retest when they imagined genetic risk feedback that challenges both enhancement and consistency motives. PMID- 24222510 TI - MorphoNeuroNet: an automated method for dense neurite network analysis. AB - High content cell-based screens are rapidly gaining popularity in the context of neuronal regeneration studies. To analyze neuronal morphology, automatic image analysis pipelines have been conceived, which accurately quantify the shape changes of neurons in cell cultures with non-dense neurite networks. However, most existing methods show poor performance for well-connected and differentiated neuronal networks, which may serve as valuable models for inter alia synaptogenesis. Here, we present a fully automated method for quantifying the morphology of neurons and the density of neurite networks, in dense neuronal cultures, which are grown for more than 10 days. MorphoNeuroNet, written as a script for ImageJ, Java based freeware, automatically determines various morphological parameters of the soma and the neurites (size, shape, starting points, and fractional occupation). The image analysis pipeline consists of a multi-tier approach in which the somas are segmented by adaptive region growing using nuclei as seeds, and the neurites are delineated by a combination of various intensity and edge detection algorithms. Quantitative comparison showed a superior performance of MorphoNeuroNet to existing analysis tools, especially for revealing subtle changes in thin neurites, which have weak fluorescence intensity compared to the rest of the network. The proposed method will help determining the effects of compounds on cultures with dense neurite networks, thereby boosting physiological relevance of cell-based assays in the context of neuronal diseases. PMID- 24222511 TI - A distance- and orientation-dependent energy function of amino acid key blocks. AB - Blocks are the selected portions of amino acids. They have been used effectively to represent amino acids in distinguishing the native conformation from the decoys. Although many statistical energy functions exist, most of them rely on the distances between two or more amino acids. In this study, the authors have developed a pairwise energy function "DOKB" that is both distance and orientation dependent, and it is based on the key blocks that bias the distal ends of side chains. The results suggest that both the distance and the orientation are needed to distinguish the fine details of the packing geometry. DOKB appears to perform well in recognizing native conformations when compared with six other energy functions. Highly packed clusters play important roles in stabilizing the structure. The investigation about the highly packed clusters at the residue level suggests that certain residue pairs in a low-energy region have lower probability to appear in the highly packed clusters than in the entire protein. The cluster energy term appears to significantly improve the recognition of the native conformations in ig_structal decoy set, in which more highly packed clusters are contained than in other decoy sets. PMID- 24222512 TI - Synthesis and antimicrobial activity of alpha-aminoboronic-containing peptidomimetics. AB - A library of 175 dipeptidomimetics and tripeptidomimetics containing an alpha amino boronic acid or boronate has been synthesized, and the activity toward Mycobacterium tuberculosis, Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa has been screened. Although there is no clear structure-activity relationship, several compounds exhibit promising activity against different pathogens. PMID- 24222513 TI - A legend of the SNARE complex and synaptotagmin-the insight into synaptic transmission. PMID- 24222515 TI - Accurate masses for structure confirmation. PMID- 24222514 TI - A prospective analysis of smoking and human papillomavirus infection among men in the HPV in Men Study. AB - At present it is unknown whether the higher prevalence of human papillomavirus (HPV) infection among smokers in men is attributed to a higher probability of acquiring an infection or because of longer infection persistence. Thus, we investigated the role of smoking on the incidence (acquisition) and clearance (persistence) of genital HPV infections among 4,026 men in the HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infection in men. Genital HPV infections were grouped by any, oncogenic and nononcogenic HPV infections and smoking status was categorized as current, former and never smokers. The incidence of any, oncogenic and nononcogenic HPV infections was significantly higher among current smokers compared to former and never smokers (p < 0.01). In multivariable analyses adjusting for sexual behavior and potential confounders, when compared to never smokers, current smokers exhibited significantly higher probability of acquiring any [hazard ratio (HR) = 1.23; 95% confidence interval (CI) 1.02-1.50] and nononcogenic (HR = 1.21; 95% CI 1.00-1.45) infections and a borderline significant probability for oncogenic infections (HR = 1.18; 95% CI 0.98-1.41). Although the median duration of HPV infection was generally longer among current smokers, we found no statistically significant associations in the multivariable analyses. Overall, these results demonstrated that current smoking exhibited the highest incidence and highest probability of acquiring genital HPV infections. PMID- 24222516 TI - Differentiation of isomeric C8- and N (2)-deoxyguanosine adducts of 2 acetylaminofluorene by fast-atom bombardment and tandem mass spectrometry. AB - Product-ion studies of source-produced ions corresponding to acetylated and nonacetylated N (2)- and C8-substituted aminofluorene adducts of deoxyguanosine were conducted to identify specific fragmentation pathways differentiating the isomers and to determine the influence of the acetyl group on the fragmentation of the arylamide modified deoxyguanosine adducts. The collision-induced dissociation spectra of the BHZ 2 (+) ion and other significant source-produced ions showed no evidence to suggest that ketene loss (deacetylation) resulted in significant alteration of the structure of the adducts. However, other significant ion formation processes, particularly loss of water from the N (2) substituted arylamide did appear to require rearrangement, likely involving bond formation between the carcinogen moiety (acetyl group) and the N1 or N2 position of the guanine base. The combined loss of ketene and water constitute a fragmentation pattern specific for the N (2)-arylamide, 3-(deoxyguanosin-N (2) yl)-2-acetylaminofluorene. PMID- 24222517 TI - Equilibrium space charge distribution in a quadrupole ion trap. AB - A simple model provides a basis for evaluating the ion spatial distribution in a uadrupole (Paul) ion trap and its effect on the total potential (trap potential plus space charge 3 acting on ions in the trap. By combining the pseudopotential approximation introduced by Dehmelt 25 years ago with the assumption of thermal equilibrium (leading to a Boltzmann ion energy distribution), the resulting ion spatial distribution (for ions of a single mass-to-charge ratio) depends only on total number of ions, trap pseudopotential, and temperature. (The equilibrium assumption is justified by the high helium bath gas pressure at which analytical quadrupole ion traps are typically operated.) The electric potential generated by the ion space charge may be generated from Poisson's equation subject to a Boltzmann ion energy distribution. However, because the ion distribution depends in turn on the total potential, solving for the potential and the ion distribution is no longer a simple boundary condition differential equation problem; an iterative procedure is required to obtain a self-consistent result. For the particularly convenient operating condition, (a z = -8qU/mrho 0 (2) Omega(2), and q z =-4qV mrho 0 (2) Omega(2), where U and V are direct current and radiofrequency (frequency, omega) voltages applied to the trap, m/q is ion mass to-charge ratio, and rho0 is the radius of the ring electrode at the z=0 midplane], both the pseudopotential and the ion distribution become spherically symmetric. The resulting one-dimensional problem may be solved by a simple optimization procedure. The present model accounts qualitatively for the dependence of total potential and ion distribution on number of ions (higher ion density or lower temperature flattens the total potential and widens the spatial distribution of ions) and pseudopotential (higher pseudopotential increases ion density near the center of the trap without widening the ion spatial distribution). PMID- 24222518 TI - Origins and structures of background ions produced by fast-atom bombardment of glycerol. AB - Accurate mass measurements were used to assign elemental compositions and tandem mass spectrometry was used to characterize the peak-at-every-mass background ions produced by kiloelectron-volt-particle bombardment of neat fast-atom bombardment matrices. The majority of the background ions observed in the mass spectrum of neat glycerol was identified. On the basis of the experiments with glycerol, a theory for the formation of background ions is presented. Results are discussed according to the chemical and physical changes that ygoe;on-volt-particle bombardment produces in the matrix. PMID- 24222519 TI - Fast-atom bombardment-induced condensation of glycerol with ammonium surfactants II: Time dependence of mass spectra and tandem mass spectra. AB - Studies of fast-atom bombardment (FAB)-induced condensation between trimethyltetradecylammonium cations and glycerol have been extended to consider spectral time dependence. To enhance reproducibility of time dependence, a modified FAB target was used. FAB mass spectrometry of deuterium-labeled surfactants and FAB/collision-induced dissociation (CID) of nonlabeled material demonstrate that products of condensation at the surfactant "head group" predominate early in the analysis, while tail adducts become prominent later. This time dependence correlates with the expected surface activity of the products. It is incompatible with gas-phase reaction, but consistent with reaction in the condensed phase. Subtle variations in the surface activities of various condensation products (derived from changes in the number of hydroxyls from the reactive glycerol radical or in the position of attack along the surfactant chain) are reflected in the time dependence of FAB and CID spectra. CID spectra of deuterium-labeled cations provide evidence for intramolecular hydrogen transfer from the surfactant tail to the head within a surfactant radical. This transfer shows no significant kinetic isotope effect. PMID- 24222520 TI - Determination of flux from a saddle field fast-atom bombardment gun. AB - The flux or beam density (equivalent current/area) of xenon atoms striking the sample target from a saddle field fast-atom bombardment (FAB) gun has been compared with that from a cesium ion gun mounted on the same instrument. A shielded Faraday cup mounted on the end of a solids probe was used to measure directly the flux of the Cs(+) beam. Samples of methylene blue in glycerol solution were then exposed to the ion beam at different fluxes and the extents of reduction were measured. The extent of reduction varied linearly with flux up to a value of about 1.16 * 10(13) particles s(-1) cm(-2) (1.85 MU cm(-2)); above this level, the reduction effect appeared to saturate. FAB spectra were obtained from the same dye solution by using varying settings of the FAB gun. By comparing the extents of reduction of the dye from the two guns, the flux from the atom gun could be estimated. Observation of luminescence from a CsI-coated target allowed estimation of the area of the atom beam. The atom beam "equivalent current" could then be calculated by multiplying the flux times the area. It was noted that for given settings, the flux from the atom gun depended on the physical condition of the gun electrodes. With new electrodes, a flux >= 1.16 * 10(13) particles s(-1) cm(-2) was obtained with nominal gun emission currents of 0.60-1.0 mA. Electrodes used extensively, but freshly cleaned, provided a flux of ~ 8 * 10(12) particles s(-1) cm(-2) at nominal emission currents of 0.40-1.0 mA. With dirty electrodes this flux could only be achieved at the highest (1.0 mA) emission current. This decline in performance occurs over a matter of months as a result of contamination and erosion of the electrodes during use. Such behavior can adversely affect spectral reproducibility even when nominal FAB gun voltage and emission current are carefully reproduced. PMID- 24222521 TI - Direct chemical analysis of uv laser ablation products of organic polymers by using selective ion monitoring mode in gas chromatography/mass spectrometry. AB - Trace quantities of laser ablated organic polymers were analyzed by using commercial capillary column gas chromatography/mass spectrometry; the instrument was modified so that the iaser ablation products could be introduced into the capillary column directly and the constituents of each peak in the chromatogram were identified by using a mass spectrometer. The present study takes advantage of the selective ion monitoring mode for significantly improving the sensitivity of the mass spectrometer as a detector, which is critical in anatyzing the trace quantities and confirming the presence or absence of the species of interest in laser ablated polymers. The initial composition of the laser ablated polymers was obtained by using an electron impact reflectron time-of-flight mass spectrometer and the possible structure of the fragments observed in the spectra was proposed based on the structure of the polymers. PMID- 24222522 TI - Electron impact ionization mass spectrometry and intramolecular cyclization in 2 substituted pyrimidin-4(3H)-ones. AB - Electron impact ionization mass spectrometry indicates that the behavior of W unsubstituted pyrirnidin-4-ones with CH2-R type substitution at C-2 differs from homologs that are N-substituted and/or 2-aryl- or 2-methyl-substituted. A dominant intramolecular cycliza-tion was found to occur between 3ZV (in agreement with the predominance of the 3NH tautomers) and the ortho positions of the aryl moiety in compounds with a CH2-aryl substitution at C-2. Theoretical calculations with an AMI SCFR method on 2-, 6-, and 2, 6-disubstituted pyrimidin-4-ones support the mass spectrometric observations. PMID- 24222523 TI - The mass-to-charge ratio scale. AB - Increases in the capacity for accurately measuring the mass-to-charge ratio of specific gas-phase ions justify the reconsideration and standard definition of the gas-phase mass-to-charge ratio scale and the clearly denned connection of that scale to condensed phases. We propose that the chemical mass standard for solids and the gas phase be based upon the mass of carbon-12 buckminsterfulierene ((12)C60). The mass-to-charge ratio scale in the gas phase would be based upon the mass of gas-phase (12)C60, the mass of the electron, and the electron charge in atomic units. As mass measurement accuracy improves, corrections to this mass to-charge ratio standard are anticipated for the vaporization energy of the 12C60 molecule and its ionization potential or electron affinity. We propose that the positive ion scale be set by the mass-to-charge ratio of (12)C 60 (+) as (+)719.9994514+/-0.0000004 u per electron charge. We propose that the negative ion mass scale be set by the mass-to-charge ratio of (12)C 60 (-) as ( )720.0005484+/-0.0000004 u per electron charge. PMID- 24222525 TI - Contextual compound screening for improved therapeutic discovery. AB - Cellular behaviors are governed by combinations of systemic and microenvironmental factors; together, these regulate cell signaling responses to growth factors. This contextual microenvironmental influence also determines drug sensitivity. Hence using in vitro systems that model contextual cellular behavior is highly beneficial for effective therapeutic development. Angiogenesis (formation of blood vessels) is driven by a series of dynamic endothelial cell signaling responses to growth factors under the influence of the vascular extracellular matrix and adjacent pericytes. In vitro primary human vascular cell co-cultures self-assemble into capillary-like structures through reciprocal heterotypic interactions that mimic angiogenic context dynamics. By using temporal live-cell imaging-based analysis, unique angiogenic microenvironments can be delineated to quantify the contextual activity of compound inhibitors. We used this in vitro organotypic contextual screening approach to conduct structure activity relationship analysis on a combretastatin A-4 analogue series to identify novel compounds with potent vascular disrupting activity in vivo. PMID- 24222526 TI - Culturally sensitive group therapy for Turkish patients suffering from chronic pain: a randomised controlled intervention trial. AB - SUMMARY OF BACKGROUND DATA: The incidence of chronic pain is higher among immigrants in Europe than among the native European population. Therapeutic interventions in this population are far less effective than in patients for whom these programmes were originally developed. OBJECTIVES: In a randomised trial, we investigated whether a cognitive behavioural treatment (CBT) programme supplemented with culturally sensitive aspects (CsCBT) improves pain intensity, pain disability and quality of life among immigrant patients, compared with a treatment of culturally sensitive exercise therapy (CsET) alone. Furthermore, we investigated whether healthcare costs would decrease. METHODS: First-generation Turkish immigrants residing in Switzerland (20-65 years of age) who suffered from chronic pain were enrolled in the trial. Patients were randomised to attend either CsCBT or CsET. The CsCBT intervention was based upon a manualised cognitive-behavioural group treatment programme for chronic pain patients and adapted to the needs of a Turkish immigrant population. The CsET intervention was based on principles of exercise therapy for treatment of nonspecific low back pain. RESULTS: A total of 116 outpatients were recruited between October 2004 and November 2006. The intervention was completed by 89 patients (77%). A total of 78 subjects (67%) completed follow-up, 12 months after the completion of the intervention programme. The intervention showed no effects in reducing pain, pain disability or quality of life. The analysis of healthcare utilisation yielded no intervention effect. CONCLUSIONS: Cognitive behavioural intervention is feasible with immigrants with chronic disabling pain, but the evidence-based CBT programme, as well as exercise therapy supplemented with culturally sensitive aspects, showed no improvement. PMID- 24222527 TI - Can local corticosteroid injection in the retrocalcaneal bursa lead to rupture of the Achilles tendon and the medial head of the gastrocnemius muscle? AB - PURPOSE: The purpose of the study is to explain the cause-effect relationship in three patients who reported combined ruptures of the Achilles tendon and the gastrosoleus complex 6 months after they had received corticosteroids injections for the management of retrocalcaneal bursitis. METHODS: Three cryopreserved cadavers (three men, three left legs) were examined to assess the anatomic connection between the retrocalcaneal bursa and the Achilles tendon (distal and anterior fibers). Blue triptan medium contrast was injected. RESULTS: An unexpected connection between the retrocalcaneal bursa and the anterior fibers of the Achilles tendon was found in all instances. CONCLUSIONS: Local corticosteroid injection of the retrocalcaneal bursa may help the symptoms of retrocalcanear bursitis, but pose a risk of Achilles tendon rupture. This risk-benefit has to be taken into account when corticosteroid injections are prescribed to professional and high-level athletes. PMID- 24222528 TI - Synthesis and anti-cancer activity of a glycosyl library of N-acetylglucosamine bearing oleanolic acid. AB - N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of saponins with potent anti-tumor activity. In order to study the structure-activity relationship of GNTS, 24 oleanolic acid saponins with (1 --> 3)-linked, (1 --> 4)-linked, (1 --> 6)-linked N-acetylglucosamine oligosaccharide residues were synthesized in a combinatorial and concise method. The cytotoxicity of these compounds toward the leukemia cell line HL-60 and the colorectal cancer cell line HT-29 could not be improved. Half maximal inhibition below 10 MUM was achieved in one single case. The study revealed that the activity decreased following the order of 3' > 4' > 6' glycosyl modifications. GNTS that incorporated (D/L)-xylose and L-arabinose at positions 3' and 4' were more potent than those bearing other sugars. PMID- 24222529 TI - Stress and eating disorder behavior in anorexia nervosa as a function of menstrual cycle status. AB - OBJECTIVE: Fluctuations in ovarian hormones during the menstrual cycle and psychosocial stress contribute to eating disorder (ED) behavior. METHOD: Using ecological momentary assessment techniques, this study examined relationships between stress and binge eating, self-induced vomiting, and dietary restriction based on menstrual cycle status in anorexia nervosa (AN). One hundred nine females with full and subthreshold AN (17-45 years old) recorded ED behavior and stress ratings over 2 weeks. Using hierarchical linear modeling, individuals with eumenorrhea and those with amenorrhea or oligomenorrhea were compared. RESULTS: Following episodes of meal skipping, momentary stress decreased in individuals with normal menstrual cycles and increased in those with irregular menstrual cycles. DISCUSSION: Results suggest that changes in stress severity in response to food restriction may differ based on ovarian hormonal status and may be a mechanism by which AN is maintained in individuals without menstrual disturbance. PMID- 24222530 TI - WISC-III cognitive profiles in children with developmental dyslexia: specific cognitive disability and diagnostic utility. AB - This study analysed the usefulness of the Wechsler Intelligence Scale for Children-Third Edition in identifying specific cognitive impairments that are linked to developmental dyslexia (DD) and the diagnostic utility of the most common profiles in a sample of 100 Portuguese children (50 dyslexic and 50 normal readers) between the ages of 8 and 12 years. Children with DD exhibited significantly lower scores in the Verbal Comprehension Index (except the Vocabulary subtest), Freedom from Distractibility Index (FDI) and Processing Speed Index subtests, with larger effect sizes than normal readers in Information, Arithmetic and Digit Span. The Verbal-Performance IQs discrepancies, Bannatyne pattern and the presence of FDI; Arithmetic, Coding, Information and Digit Span subtests (ACID) and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profiles (full or partial) in the lowest subtests revealed a low diagnostic utility. However, the receiver operating characteristic curve and the optimal cut-off score analyses of the composite ACID; FDI and SCAD profiles scores showed moderate accuracy in correctly discriminating dyslexic readers from normal ones. These results suggested that in the context of a comprehensive assessment, the Wechsler Intelligence Scale for Children-Third Edition provides some useful information about the presence of specific cognitive disabilities in DD. Practitioner Points. Children with developmental dyslexia revealed significant deficits in the Wechsler Intelligence Scale for Children-Third Edition subtests that rely on verbal abilities, processing speed and working memory. The composite Arithmetic, Coding, Information and Digit Span subtests (ACID); Freedom from Distractibility Index and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profile scores showed moderate accuracy in correctly discriminating dyslexics from normal readers. Wechsler Intelligence Scale for Children-Third Edition may provide some useful information about the presence of specific cognitive disabilities in developmental dyslexia. PMID- 24222532 TI - Care ethics for guiding the process of multiple sclerosis diagnosis. AB - Multiple sclerosis (MS) is a chronic neurological disorder for which there is no definitive diagnostic test. Uncertainty characterises most of its features with diagnosis reached through a process of elimination. Coping with uncertainty has been recognised as a significant problem for MS patients. Discussions in the literature concerning the ethics of MS diagnosis have focused on an ethics of duty emphasising the rules for disclosure and healthcare professionals' obligations to provide information to patients. This narrow construal of the ethics at stake with MS diagnosis may be driven by a common misperception that diagnosis is an event, or series of events, rather than a process. Scant attention has been given to the dynamic, situated relational space between patient and physician as they journey potentially together (or apart) through the process of diagnosis. The healthcare provider cannot properly judge 'the how, what and when' of MS disclosure merely by applying rules pertaining to general professional duties to tell the truth and patients' rights to know their medical status. Proper disclosure and effective communication require the practice of flexible, caring responsibility and sustained, ongoing attention to the particular relational needs of 'this' patient in her own situational context. Accordingly, this article argues that care ethics is especially useful (but not without certain limitations) for attending to a broader swath of responsibilities (different from minimal duties) and affective components implicated in meeting patients' overall needs for care as the patient and physician cope with uncertainty through the process of establishing an MS diagnosis. PMID- 24222531 TI - Structure-activity relationships of peptidomimetics that inhibit PPI of HER2 HER3. AB - Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase family protein receptor that is known to undergo heterodimerization with other members of the family of epidermal growth factor receptors (EGFR) for cell signaling. Overexpression of HER2 and deregulation of signaling has implications in breast, ovarian, and lung cancers. We have designed several peptidomimetics to block the HER2-mediated dimerization, resulting in antiproliferative activity for cancer cells. In this work, we have investigated the structure-activity relationships of peptidomimetic analogs of Compound 5. Compound 5 was conformationally constrained by N- and C-terminal modification and cyclization as well as by substitution with d-amino acids at the N-and C-termini. Among the compounds studied in this work, a peptidomimetic Compound 21 with d-amino acid substitution and its N- and C termini capped with acetyl and amide functional groups and a reversed sequence compared to that of Compound 5 exhibited better antiproliferative activity in HER2-overexpressed breast, ovarian, and lung cancer cell lines. Compound 21 was further evaluated for its protein-protein interaction (PPI) inhibition ability using enzyme fragment complementation assay, proximity ligation assay, and Western blot analysis. Results suggested that Compound 21 is able to block HER2:HER3 interaction and inhibit phosphorylation of the kinase domain of HER2. The mode of binding of Compound 21 to HER2 protein was modeled using a docking method. Compound 21 seems to bind to domain IV of HER2 near the PPI site of EGFR:HER2, and HER:HER3 and inhibit PPI. PMID- 24222533 TI - Altered postprandial responses in gastric myoelectrical activity and cardiac autonomic functions in healthy obese subjects. AB - BACKGROUND: It is unknown whether gastric myoelectrical activity (GMA) and autonomic functions are altered in obesity. The aims of this study were to investigate GMA and autonomic functions in obese subjects and to compare their responses to different meals with lean subjects. METHODS: The study was performed in 12 lean and 12 obese subjects. GMA was measured using electrogastrography, and autonomic functions were assessed using spectral analysis of heart rate variability. RESULTS: The study achieved the following key results: (1) Compared to lean subjects, obese subjects showed unaltered gastric slow waves at baseline but enhanced responses to both fatty and protein meals. The lean subjects showed a reduced percentage of normal gastric slow waves with a fatty meal, which was not seen in obese subjects; lean subjects showed no changes in the dominant frequency or power of the gastric slow waves with a protein meal, whereas both of these parameters were increased in obese subjects. (2) Autonomic functions were altered in obese subjects in both fasting and fed states. Obese subjects showed an increased sympathetic activity in the fasting state, but absence of a normal postprandial response in sympathovagal balance to both fatty and protein meals. CONCLUSIONS: The findings on gastric slow waves demonstrate that obese subjects are more receptive to fatty meals and more responsive to protein meals. Obese subjects have impaired autonomic functions in both fasting and fed states. The alterations in gastric and autonomic functions may contribute to eating disorders in the obese. PMID- 24222534 TI - Comparison of weight loss and body composition changes in morbidly obese Taiwanese patients with different bariatric surgeries: a 1-year follow-up study. AB - BACKGROUND: This study investigated the impacts of two different bariatric surgeries on the body composition of morbidly obese patients in Taiwan. Also, the differences in body composition changes between genders were compared. METHODS: In total, 198 patients who underwent bariatric surgery were included, with 130 receiving a sleeve gastrectomy (SG) and 68 receiving adjusted gastric banding (AGB). The weight and body composition were measured by bioelectrical impedance. Follow-up examinations were performed at subsequent visits after surgery and at 1 year. Only 81 SG and 40 AGB patients continued follow-up for the entire 12 months. RESULTS: All patients experienced significant weight loss beginning from 3 months after surgery. Compared to patients with AGB, SG patients had a greater extent of body mass index (BMI) loss, whereas a greater muscle weight percentage increase was found compared to AGB patients. Female patients had a higher body fat mass and lower muscle weight percentage and BMI than did males. There were no differences in changes in BMI, or percentages of body fat and muscle mass between male and female patients for 12 months after surgery. However, the waist/hip ratio (WHR) decrement and percentage of excess weight loss (ExWL%) were significantly greater in female than male patients with both bariatric surgeries. CONCLUSIONS: These findings suggest that although females had greater extents of WHR decrement and ExWL% than male patients with both surgical procedures, patients who received SG had higher BMI changes and body fat losses than SGB patients regardless of differences in the gender distribution. PMID- 24222535 TI - The effect of laparoscopic gastric bypass on dyslipidemia in severely obese patients: a 5-year follow-up analysis. AB - BACKGROUND: Dyslipidemia is common in the morbidly obese population. A previous study from our institution demonstrated improved lipid parameters 1 and 2 years after laparoscopic Roux-en-Y gastric bypass (LRYGB) with fewer patients taking lipid-modifying medications postoperatively, suggesting cost-savings over time. Our objective was to evaluate lipid parameters and lipid-modifying medication use at 5 years postoperative. METHODS: The medical records of patients who underwent LRYGB from September 2001 through July 2008 were reviewed. Inclusion criteria consisted of both preoperative and 5-year postoperative lipid values available. RESULTS: Six hundred eighty-two patients underwent LRYGB during the study period; 450 had data available at 5 years postoperative, and 187 patients met the inclusion criteria. Mean age was 46.3 years, and 83 % were women. Mean preoperative body mass index was 47.4 kg/m(2). Total cholesterol was 191.2 +/- 35.4 preoperatively and 181.1 +/- 33.0 at 5 years postoperative (P = 0.003). Low density lipoprotein (LDL) was 107.9 +/- 30.9 preoperatively and 95.3 +/- 29.7 at 5 years postoperative (P < 0.001). High-density lipoprotein (HDL) was 48.7 +/- 12.8 preoperatively and 65.1 +/- 18.0 at 5 years postoperative (P < 0.001). Triglycerides were 171.3 +/- 78.6 preoperatively and 112.9 +/- 60.7 5 years postoperative (P < 0.001). Preoperatively, 35 % of patients were on lipid modifying medications, and at 5 years postoperatively, 26 % required lipid modifying medications (P = 0.002). CONCLUSIONS: Patients who have undergone LRYGB continue to show favorable change in their lipid profiles at 5 years postoperative. Furthermore, fewer patients were taking lipid-modifying medications at 5 years postoperatively than preoperatively. PMID- 24222537 TI - Single-cell printer: automated, on demand, and label free. AB - Within the past years, single-cell analysis has developed into a key topic in cell biology to study cellular functions that are not accessible by investigation of larger cell populations. Engineering approaches aiming to access single cells to extract information about their physiology, phenotype, and genotype at the single-cell level are going manifold ways, meanwhile allowing separation, sorting, culturing, and analysis of individual cells. Based on our earlier research toward inkjet-like printing of single cells, this article presents further characterization results obtained with a fully automated prototype instrument for printing of single living cells in a noncontact inkjet-like manner. The presented technology is based on a transparent microfluidic drop-on demand dispenser chip coupled with a camera-assisted automatic detection system. Cells inside the chip are detected and classified with this detection system before they are expelled from the nozzle confined in microdroplets, thus enabling a "one cell per droplet" printing mode. To demonstrate the prototype instrument's suitability for biological and biomedical applications, basic experiments such as printing of single-bead and cell arrays as well as deposition and culture of single cells in microwell plates are presented. Printing efficiencies greater than 80% and viability rates about 90% were achieved. PMID- 24222539 TI - Advance care planning is everybody's business. PMID- 24222540 TI - Comparison of three thiol probes for determination of apoptosis-related changes in cellular redox status. AB - An early step in apoptosis is extrusion of reduced glutathione (GSH). Current assays for measuring apoptosis involve a number of incubation and washing steps, making them time consuming and laborious. Using two novel thiol reactive agents (VitaBright-43 and VitaBright-48) and a GSH specific probe; monochlorobimane, we investigated whether changes in the level of free thiols can be used as an apoptotic marker. Upon addition to cells the probes permeate the cell membrane and react with intracellular thiols, causing cellular fluorescence. Cytometric quantification of the cell fluorescence (without washing) can then be used to determine the population's cellular thiol level at the single cell level. Apoptotic traits such as phosphatidylserine externalisation, caspase activity and mitochondrial potential were investigated at different time points after induction of apoptosis and correlated to changes detected using the thiol probes. We found that though all three thiol probes could be used to detect changes in the level of free thiols correlating well with apoptotic markers, other properties such as detection of early versus late apoptosis and staining kinetics differed among the three probes. However, we suggest adding evaluation of the level of free thiols to the list of phenotypes which may be measured in order to detect apoptosis, as this provides a reliable and easy way of assaying apoptosis. PMID- 24222541 TI - Conformer selection of protein ions by ion mobility in a triple quadrupole mass spectrometer. AB - Electrospray mass spectra of multiply charged protein molecules show two distinct charge state distributions proposed to correspond to a more highly charged, open conformational form and a lower charged, folded form. Elastic collisions carried out in the radiofrequency-only collision cell of a triple quadrupole mass spectrometer have dramatic effects on the appearance of the mass spectra. The different cross sectional areas of the conformers allow preferential selection of one charge state distribution over the other on the basis of ion mobility. Preferential selection is dependent on the nature and pressure of the target gas as well as the nature of the protein. In the case of positively charged horse heart apomyoglobin (MW 16,951 da), a high charge state distribution centered around (M + 20H)(20+) predominates at low target gas pressures and a second distribution centered around (M + 10H)(10+) predominates at high target gas pressures. Bimodal distributions are observed at intermediate pressures and, remarkably, charge states between the two distributions are not effectively populated under most of the conditions examined. Hard sphere collision calculations show large differences in collision frequencies and in the corresponding kinetic energy losses for the two conformational states and they demonstrate that the observed charge state selectivity can be explained through elastic collisions. PMID- 24222542 TI - Gas-phase anionic complexes of alkali metal ions and peptides: Structure and collision activated decompositions. AB - Alkali metal ions and anionic peptides can be desorbed into the gas phase to give metal-bound peptides and bis(peptide) complexes bearing a - 1 charge. Although amide nitrogens of peptide bonds are deprotonated in the gas phase by alkali metal ions, this reacion does not occur in solution. Metal-bound dipeptide anions exist as a single structure, whereas those of tripeptide complexes have three structures as revealed by tandem mass spectrometric studies. Ions of bis(peptide) complexes of alkali metals decompose upon collisional activation principally to form deprotonated peptides, in contrast to bis(peptide) complexes of alkaline earth metal ions, which undergo elimination of a neutral peptide. PMID- 24222543 TI - Fast-atom bombardment tandem mass spectrometry of [(13)C]arachidonic acid labeled phospholipid molecular species. AB - A method employing stable isotope labeling and fast-atom bombardment (FAB) tandem mass spectrometry has been developed to directly assess events of biosynthesis and metabolism of arachidonic acid containing phospholipid molecular species by cells carried in culture. Mast cells, cultured with [(13)C]linoleic acid, converted this precursor into arachidonic acid which was then incorporated into cellular phospholipids. Over a 24 hour period, the extent of label enrichment in each arachidonate-containing phospholipid molecular species was monitored by using negative FAB ionization with selected reaction monitoring. Specific incorporation of [(13)C17] labeled arachidonate was determined from the ratio of the carboxylate anions at m/z 320 and 303, which correspond to [(13)C17]arachidonate and unlabeled arachidonate, respectively, produced by collision-induced dissociation of each specific molecular anion. The use of [(13)C]linoleic acid as a precursor of arachidonic acid avoids the problem of changing the endogenous pool size by directly adding labeled arachidonic acid. Measurement of the [(13)C17]label also avoids interferences from endogenous isobaric fatty acids that are naturally present at low levels. PMID- 24222544 TI - Fast-atom bombardment and tandem mass spectrometry of macrolide antibiotics. AB - Molecular weights of macrolide antibiotics can be determined from either (M + H)(+) or (M + Met)(+), the latter desorbed from alkali metal salt-saturated matrices. The ion chemistry of macrolides, as determined by tandem mass spectrometry (MS/MS), is different for ions produced as metallated than those formed as (M + H)(+) species. An explanation for these differences is the location of the charge. For protonated species, the charge is most likely situated on a functional group with high proton affinity, such as the dimethylamino group of the ammo sugar. The alkali metal ion, however, is bonded to the highly oxygenated aglycone. As a result, the collision-activated dissociation spectra of protonated macrolides are simple with readily identifiable fragment ions in both the high and low mass regions but no fragments in the middle mass range. In contrast, the cationized species give complex spectra with many abundant ions, most of which are located in the high mass range. The complementary nature of the fragmentation of these two species recommends the study of both by MS/MS when determining the structure or confirming the identity of these biomaterials. PMID- 24222545 TI - On the stabilization of carbanions by adjacent phenyl, cyano, methoxy-carbonyl, and nitro groups in the gas phase. AB - Institute of Mass Spectrometry, University of Amsterdam, Amsterdam, The Netherlands By using the method of Fourier transform ion cyclotron resonance mass spectrometry, substituent stabilization energies of homologous series of cycloalkyl carbanions, Xi-c-CnH2n-2 (n = 3, 4, 5, 6, 7) with pi-accepting substituents (Xi = Ph, CN, COOMe, NO2) have been determined experimentally in the gas phase as the difference between the proton affinity of the substituted and corresponding unsubstituted (Xi = H) cycloalkyl carbanions.The stabilization energy data have been analyzed in terms of Taft's parametrization of polarizability, field/inductive, and resonance effects. The linear regression analyses show excellent correlations within the XiCH2 (-) Xi-c-CnH2n-2 (-) (n = 4, 5, 6, 7), and Xi-c-C3H4 (-) carbanion series, from which it appears that the contributions of polarizability effects are independent of the above type of carbanions and only depend on the nature of the substituent.Further, it follows that inductive stabilization is more effective in the substituted methyl, XiCH2 ( ), than in the substituted cycloalkyl, Xi-c-CnH2n-2 (-) (n = 4, 5, 6, 7) carbanions. This result suggests that inductive stabilization is counteracted by the electron releasing effect of alkyl groups.Resonance stabilization is significantly more effective in the substituted cycloalkyl, Xi-c-CnH2n-2 (-) (n = 4, 5, 6, 7), than in the substituted methyl, XiCH2 (-), carbanions, which suggests that m contrast to inductive stabilization, resonance stabilization is assisted by the electron releasing effect of alkyl groups.Finally, it appears that substitutent stabilization in the geometrically restricted substituted cyclopropyl carbanions, Xi-c-C3H4 (-), is dramatically less effective than in the corresponding geometrically unrestricted larger substituted cycloalkyl carbanions, Xi-c-CnH2n-2 (-) (n = 4, 5, 6, 7). The linear regression analyses of the substituted cycloalkyl carbanions indicate that reduction of the stabilization energy is caused not exclusively by a geometrically hindered resonance stabilization, but also to a smaller extent by a less efficient inductive stabilization in the substituted cyclopropyl carbanions. PMID- 24222546 TI - Gas-phase ion-molecule chemistry of borate and boronate esters. AB - Borate esters B(OR)3 and boronate esters RB(OR)2 undergo ion-molecule reactions to yield both addition products (by an implied radiative emission mechanism), ligand exchange, and proton transfer products, in both positive and negative ion modes. Although an acidity for CH3B(OR)2 could not be determined, HOB(OR)2 has an acidity between acetaldehyde and nitromethane. In light of the negligible polar electron acceptor properties of the -B(OR)2 group, that functionality must therefore be one of the best resonance electron acceptor groups known, almost half again as effective as the nitro group. PMID- 24222547 TI - Atmospheric pressure chemical ionization of alkanes, alkenes, and cycloalkanes. AB - Normal and cyclic alkanes and alkenes form stable gas-phase ions in air at atmospheric pressure from 40 to 200 degrees C when moisture is below 1 ppm. Ionization of alkanes in a (63)Ni source favored charge transfer over proton transfer through pathways involving [M-1](+) and [M-3](+) ions. Ion mobility spectra for alkanes showed sharp and symmetrical profiles while spectra for alkenes suggested fragmentation. Ion identifications were made by using mass spectrometry, and ionization pathways were supported by using deuterated analogs of alkanes and alkenes. Alkanes were ionized seemingly through a hydrogen abstraction pathway and did not proceed through an alkene intermediate. New methods for interpretation of mobility spectra utilizing ion mobility spectrometry, atmospheric pressure chemical ionization mass spectrometry, chemical ionization mass spectrometry, and ion mobility spectrometry-mass spectrometry data were demonstrated. PMID- 24222548 TI - On the origin of some controversial ions (m/z 59, 60, 77, and 119) in the thermospray reagent plasma from ammonium acetate. AB - The origin of ions at m/z 60, 77, and 119 in the thermospray (TSP) reagent plasma is reconsidered. It is demonstrated that these major ions in the TSP spectrum of ammonium acetate are not due to dehydration processes in the gas or liquid phase, as is generally accepted, but to the preexistence of acetamide as an impurity in the commercial salts. Acetamide, characterized by TSP/tandem mass spectrometry, gas chromatography-electron impact ionization mass spectrometry, (1)H-NMR, and (13)C-NMR, is responsible for the [M +60](+) and [M + 77](+) adducts observed in some spectra. The buffer ion at m/z 59 is also due to impurities in the ammonium acetate salts. Washing the solid salt with chloroform eliminates most of these impurities. Examples using the pesticides linuron, monuron, and carbaryl show that the ions observed at m/z Mr + 60 and Mr + 59 disappear when a buffer obtained from acetic acid and ammonia is used instead of the commercial salts. PMID- 24222549 TI - Improved detection limits for electrospray ionization on a magnetic sector mass spectrometer by using an array detector. AB - Array detection was compared with point detection for solutions of hen egg-white lysozyme, equine myoglobin, and ubiquitin analyzed by electrospray ionization with a magnetic sector mass spectrometer. The detection limits for samples analyzed by using the array detector system were at least 10 times lower than could be achieved by using a point detector on the same mass spectrometer. The minimum detectable quantity of protein corresponded to a signal-to-background ratio of approximately 2?1 for a 500 amol/MUL solution of hen egg-white lysozyme. However, the ultimate practical sample concentrations appeared to be in the 10 100 fmol/MUL range for the analysis of dilute solutions of relatively pure proteins or simple mixtures. PMID- 24222550 TI - Observation of noncovalent complexes to the avidin tetramer by electrospray ionization mass spectrometry. AB - Intact avidin-biotin and avidin-biotin maleimide noncovalent complexes have been observed by electrospray ionization mass spectrometry (ESI-MS) by using an extended mass range quadrupole mass spectrometer. By utilizing mild ES1 interface conditions, the expected solution behavior of four biotin or biotin maleimide molecules noncovalently binding to each avidin tetramer can be preserved in the gas phase. The ESI-MS results show the appropriate mass additions of 973 +/- 60 Da for biotin and 1802 +/- 40 Da for biotin maleimide to the avidin tetramer species. These results support the hypothesis that substantial retention of higher order structure is possible in the gas phase by using gentle ESI conditions. PMID- 24222552 TI - A predicted immunity protein confers resistance to pyocin S5 in a sensitive strain of Pseudomonas aeruginosa. PMID- 24222553 TI - Complications of total hip arthroplasty: periprosthetic fractures of the acetabulum. AB - Periprosthetic fractures of the acetabulum are a rare but potentially disastrous complication of total hip arthroplasty. Such fractures occur either as early perioperative complications or late complications when they are associated with either significant trauma or as a result of the loss of the structural integrity of the bone supporting the prosthesis, such as aseptic osteolysis. The incidence of such fractures appears to be increasing with the increased use of uncemented acetabular components. This article explores the current literature on the epidemiology, etiology, and classification of periprosthetic acetabular fractures as well as offering potential treatment strategies. PMID- 24222554 TI - Biogenic tellurium nanorods as a novel antivirulence agent inhibiting pyoverdine production in Pseudomonas aeruginosa. AB - While antibiotic resistance in bacteria is rapidly increasing, the development of new antibiotics has decreased in recent years. Antivirulence drugs disarming rather than killing pathogens have been proposed to alleviate the problem of resistance inherent to existing biocidal antibiotics. Here, we report a nontoxic biogenic nanomaterial as a novel antivirulence agent to combat bacterial infections caused by Pseudomonas aeruginosa. We synthesized, in an environmentally benign fashion, tellurium nanorods (TeNRs) using the metal reducing bacterium Shewanella oneidensis, and found that the biogenic TeNRs could effectively inhibit the production of pyoverdine, one of the most important virulence factors in P. aeruginosa. Our results suggest that amyloids and extracellular polysaccharides Pel and Psl are not involved in the interactions between P. aeruginosa and the biogenic TeNRs, while flagellar movement plays an important role in the cell-TeNRs interaction. We further showed that the TeNRs (up to 100 ug/mL) did not exhibit cytotoxicity to human bronchial epithelial cells and murine macrophages. Thus, biogenic TeNRs hold promise as a novel antivirulence agent against P. aeruginosa. PMID- 24222555 TI - Clinical features, testing, and management of patients with suspected prosthetic hip-associated cobalt toxicity: a systematic review of cases. AB - Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations. PMID- 24222556 TI - The effects of maternal eating disorders on offspring childhood and early adolescent psychiatric disorders. AB - OBJECTIVE: There is evidence that parental psychiatric disorders are associated with offspring psychiatric disorder. Very few small studies have investigated the effect of maternal eating disorders on offspring psychopathology throughout childhood and early adolescence. We aimed to investigate psychiatric disorders at age 7, 10, and 13 years in offspring of women with eating disorders prior to pregnancy and investigate the relative contribution of other psychiatric disorders. METHOD: Women (N = 12,035) from a large population-based longitudinal cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). A brief prepregnancy psychiatric history was obtained at enrollment to determine exposure. Offspring psychiatric disorder was measured using the developmental and well-being assessment at ages 7, 10, and 13. RESULTS: Maternal eating disorders were associated with a psychiatric diagnosis in the offspring at age 7 and 10, particularly emotional disorders (Odds ratio = 1.9, 95%CI: 1.1-2.8). Maternal psychiatric disorders other than eating disorders predicted psychiatric diagnoses across ages, and acted in an additive fashion with maternal eating disorders. DISCUSSION: Maternal eating disorders together with comorbid psychopathology increase risk for psychiatric disorders in childhood and early adolescence, in particular for emotional disorders. This has important implications for prevention and future research. PMID- 24222557 TI - Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer. AB - BACKGROUND: Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival. METHODS: We included 46 patients with known information on the family history of breast or ovarian cancer recorded at the Geneva Cancer Registry between 1970 and 2009. We compared patients with and without a family history with chi-square of heterogeneity, risk of second cancer with standardised incidence ratios (SIRs), and overall survival by Kaplan-Meier methods. RESULTS: Approximately 20% of men with breast cancer had a positive family history. No differences were observed between men with and without familial risk except that patients with increased risk were more likely to receive radiotherapy and hormone therapy when compared with patients without familial risk. This more complete therapy is likely to be explained by the heightened awareness of cancer treatment among breast cancer patients with affected family members. Six men developed a second cancer. SIRs for second cancer were not significantly increased among patients with or without familial risk (1.93, 95% confidence interval [CI] 0.23-6.97 and 1.04, 95% CI 0.28 2.66, respectively). Overall survival was not significantly different between the two groups. CONCLUSIONS: Prognosis was similar among patients with or without familial risk. Our results are however based on small numbers and larger registry based cohorts of males with precise data on familial risk are still warranted. PMID- 24222558 TI - Investigation of the gas-phase structure of electrosprayed proteins using ion molecule reactions. AB - Proton transfer reactions of ammonia, dimemylamine, diethylamine, and trimethylarnine with multiply protonated proteins generated by electrospray ionization (ESI) were examined to probe the relationship between solution and gas phase protein structure and the relationship with ion-molecule reactivity. The ion-molecule reactions were carried out in an atmospheric pressure capillary inlet/reactor based upon an ESI interface to a quadrupole mass spectrometer. Two types of systems were explored: (1) proteins possessing cysteine-cysteine disulfide bonds and the analogous disulfide-reduced proteins, and (2) proteins sprayed from solution compositions where the protein has different conformations. While the cysteine-cysteine disulfide-bound proteins were more reactive than equally charged disulfide-reduced proteins under these conditions, no significant reactivity differences were noted for ions arising from different solution conformations. The effect of inlet/reactor temperature on charge distributions with and without amine reagent was also explored, demonstrating that thermal denaturation of proteins can occur in heated capillary inlets. The results are discussed in the context of recent results indicating the persistence of at least some higher order protein structure in the gas phase. PMID- 24222559 TI - Selective generation of charge-cependent/independent ion energy distributions from a heated capillary electrospray source. AB - Retarding grid and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry variable trap potential measurements are performed to determine factors that contribute to the kinetic energy distribution of ions formed in an electrospray source that uses a heated capillary for desolvation. The control of ion kinetic energies is achieved by manipulating the skimmer position in the postcapillary expansion and by varying the potential appEed to the skimmer. The selective generation of either charge-dependent or charge-independent ion energy distributions is demonstrated. Charge-dependent energy distributions of electro sprayed ions are created by sampling ions near the Mach disk of the supersonic expansion and by using a larger diameter skimmer orifice; the FTICR spectra acquired under these conditions exhibit mass-to-charge ratio-dependent mass discrimination determined by the potential used to trap the ions. Charge independent energies of electrosprayed ions are created by positioning the capillary adjacent to the skimmer to sample thermal ions and by using a smaller skimmer orifice to reduce expansion cooling; under these conditions ion kinetic energy is determined primarily by the skimmer potential and no mass-to-charge ratio-dependence is observed in the selection of optimum FTICR trapping conditions. The ability to select between proteins of different conformation on the basis of kinetic energy differences is demonstrated. For example, a 0.4 V difference in trap potential is observed in the selective trapping of open and closed forms of the +10 charge state of lysozyme. Finally, it is demonstrated that by operating the source under conditions which deliver a beam of ions with charge-independent energies to the cell, it is possible to obtain precursor and product ion signal magnitudes in FTTCR spectra without charge-dependent mass discrimina-tion. PMID- 24222560 TI - Direct matrix-assisted laser desorption ionization mass spectrometric analysis of proteins immobilized on nylon-based membranes. AB - Direct analysis of proteins adsorbed onto the surface of nylon membranes has been performed at the picomole level by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Nylon-66 and positive charge-modified nylon (Zetabind) membranes fixed to MALDI probe tips were successfully employed to analyze picomole quantities of sample that were adsorbed onto these inert supports prior to adding a matrix-containing solution. Proteins and peptides are readily solubilized from these types of membrane with conventional matrix solvents and cocrystallize with the matrix on the membrane surface. Because solubilization of membrane-adsorbed protein is necessary for successful sample preparation, nylon membranes are more suitable for use with MALDI-MS than other protein transfer membranes such as polyvinylidene difluoride or nitrocellulose. When compared to samples prepared conventionally, no apparent loss of sensitivity or resolution is observed when analysis by MALDI-MS is performed from nylon-66 or positive charge-modified nylon membranes. Detection limits and resolution are not apparently affected by the membrane immobilization/washing procedure, and no change in the mass accuracy is observed when analysis is performed on the nylon surface. However, there is a time shift (increase) in ion flight time when analysis by MALDI-time-of-flight-MS is performed directly from the membrane fixed to the probe tip (about 200 ns for an ion of mass 379.3). To maintain mass accuracy, the use of internal standards or external calibration performed on a membrane support was necessary. The immobilization of proteins on nylon membranes can be used to facilitate removal of water-soluble contaminants because the sample is retained when the membrane is immersed in water prior to adding the matrix solution. The feasibility of performing both chemical and enzymatic modifications of proteins adsorbed onto inert nylon supports prior to analysis by MALDi-MS is also demonstrated. PMID- 24222561 TI - Simulated ion trajectory and induced signal in ion cyclotron resonance ion traps. AB - We present a numerical method for computation of electrostatic (trapping) and time-varying (excitation) electric fields and the resulting ion trajectory and detected time-domain-induced voltage signal in a rectangular (or cubic) ion cyclotron resonance (ICR) ion trap. The electric potential is calculated by use of the superposition principle and relaxation method with a large number of grid points (e.g., 100 * 100 * 100 for a cubic trap). Complex ICR experiments and spectra may now be simulated with high accuracy. Ion trajectories may be obtained for any combination of trapping and excitation modes, including quadrupolar or cubic trapping in static or dynamic mode; and dipolar, quadrupolar, or parametric excitation with single-frequency, frequency-sweep (chirp), or stored waveform inverse Fourier transform waveforms. The resulting ion trajectory may be represented either as its three dimensional spatial path or as two-dimensional plots of x-, y-, or z-position, velocity, or kinetic energy versus time in the absence or presence of excitation. Induced current is calculated by use of the reciprocity principle, and simulated ICR mass spectra are generated by Fourier transform of the corresponding time-domain voltage signal. PMID- 24222562 TI - Relative dissociation energy measurements using ion trap collisional activation. AB - The measured minimum resonance excitation amplitudes for decomposition of polyatomic ions in the quadrupole ion trap collisional activation experiment are shown to correlate with literature critical energies. The present article describes how experiments can be performed to derive threshold resonance excitation amplitudes via the kinetics associated with collision-induced dissociation (i.e., dissociation rate constants) in the quadrupole ion trap. The relationship between these threshold values and critical energies is established empirically by using kinetic data acquired for molecular ions with critical energies measured with other techniques. The experiments are complicated by the change in optimum resonance excitation frequency with amplitude, due presumably to contributions from higher order fields. It is proposed that the threshold resonance excitation amplitude is a measure of the change in temperature of the parent ion population required to achieve a measurable rate of decomposition. The present results indicate that the quadrupole ion trap may see new applications as a quantitative tool for the study of gaseous ion chemistry. PMID- 24222563 TI - Hydrogen-bonding interactions in gas-phase polyether/ammonium ion complexes. AB - Hydrogen bonds are among the most important interactions involved in selective complexation in host-guest chemistry. In this study a variety of hydrogen-bonded crown ether/ammonium ion complexes are generated in the gas phase by association reactions between an amine substrate and a polyether, one of which is initially protonated, and stabilized by many collisions in the chemical ionlzation source of a triple quadrupole mass spectrometer or in a quadrupole ion trap. The nature of the hydrogen-bonding interactions of the ion complexes are evaluated by comparison of their collision-activated dissociation spectra. After collisional activation, those complexes that are weakly bound dissociate to form intact protonated polyether molecules and/or ammonium ions by simple cleavages of the hydrogen-bond association interactions. In contrast, those complexes strongly bound by multiple hydrogen bonds dissociate not only to the protonated polyether and/or ammonium ions but also by extensive covalent bond cleavage of the protonated ether skeleton.This latter type of dissociation behavior suggests that the polyether/ammonium ion complexes may be sufficiently strongly bound that surpassing the high barrier to decomposition results in formation of internally excited polyether molecules that may then undergo subsequent fragmentation by skeletal cleavages. Moreover, complexes involving multiple hydrogen bonds may have slower dissociation kinetics, allowing competition from fast dissociation processes that have substantial energy barriers. PMID- 24222564 TI - Protonation of ferrocene in the gas phase. AB - Hydrogen-deuterium exchange, proton and deuteron transfer, and collision-induced dissociation experiments involving protonated ferrocene, [Fe(cC5H5)2]H(+), and isotopically labeled analogues have been carried out using a Fourier transform ion cyclotron resonance (FTICR) spectrometer and a double-focusing mass spectrometer of reversed geometry. These experiments reveal that the structure in which the added proton is bound to one of the cyclopentadienyl rings, possibly via agostic interaction with the iron atom, plays an important role in the gas phase behavior of protonated ferrocene. It is demonstrated that extensive hydrogen atom scrambling occurs in the cyclopentadiene ring and that the extra hydrogen can also switch from one ring to the other, probably via the iron atom. An interpretation is presented which implicates slow thermal unimolecular rearrangement on the FKR time scale from a metal-protonated form to a ring protonated form which is higher in energy. This interpretation successfully rationalizes the current data as well as previous gas-phase measurements and is found to be in good agreement with solution and matrix isolation studies. PMID- 24222565 TI - Mechanistic study of hydrogen/deuterium exchange between [M - 1](-) ions of chlorinated benzenes and D 2O or ND 3. AB - Low-energy collisions between [M - 1](-) ions derived from the three isomers of dichlorobenzene and deuterated water and ammonia are found to produce distinctive hydrogen/ deuterium (H/D) exchange reaction product patterns. The predominant products observed for p-, m-, and o-dichlorobenzene are 1, 2, and 3 sequential deuterium exchanges, respectively. The reactivity is substantially higher for D2O than ND3 We postulate a mechanism that involves the formation of a five-membered ring intermediate. The intermediate is thought to be initiated by the attack of ND3 or D2O at the localized negative charge site on the aromatic ring. A successful exchange is followed by the relocation of the charge site to the adjacent carbon. Ion products with higher degrees of deuterium substitution than the expected predominant products of their corresponding isomers are believed to be the results of isomerization of the reactant ions occurring in the ion source. The proposed mechanism fuily explains the observed product spectra derived from al1 the isomers of chlorinated benzenes. The trends for the formation of various H/D exchange products represented by the sweated product-time plots based on the proposed mechanism compare well with the similar trends obtained from the experimental product-pressure plots. The reaction is useful for the mass spectrometric differentiation of chlorobenzene isomers. PMID- 24222566 TI - Enhancement of mass spectrometric detection of LTC4, LTD 4, and LTE 4 by derivatization. AB - Several acylating reagents are synthesized and used to introduce quatemary phosphonium or ammonium or ternary sulfonium functions into a simple model of a peptido leukotriene (PLT). One of these reagents was selected for further study with LTE4, LTD4, and LTC4. We demonstrate that acylation of the free amine function of PLTs to produce the 5-triphenylphosphoniumvaleryl-amide (TPPV) derivatives enhances chemical stabilities and significantly increases responses in fast-atom bombardment and continuous-flow liquid secondary ion mass spectrometry (CF-LSIMS) relative to the native PLTs. With high-performance liquid chromatography inlet to CF-LSIMS, we demonstrate the facile detection in selected ion monitoring of the TPPV derivative of 3 pg of LTD4. PMID- 24222567 TI - Poly(amic acid) and polyimide characterization using gas chromatography/mass spectrometry and particle beam liquid chromatography/mass spectrometry. AB - A number of polymers were hydrolyzed in NH4OH and studied using gas chromatography/ mass spectrometry (GC/MS) and particle beam liquid chromatography/mass spectrometry (particle beam LC/MS) techniques. The polymers studied in this report were as follows: BPDA-PDA, BPDA-PDA-ODA, BPDA-PDA-GFDA, PMDA-ODA, and BTDA-APB. Some of the polymer samples were hydrolyzed in both their acid and imide forms to see if any mass spectrometric differences could be detected. ln all cases, the acid and imide spectra looked the same. GC/MS was unable to determine either the amine or acid portion of these polymers via a direct injection of the sample, but when the samples were first extracted with diethyl ether and this ether extract was injected into the chromatograph, the amine portion of the polymers was readily detected. The acid portion was, again, not detected in either the sample or the ether extract. The particle beam was able to detect both the amine and acid monomeric units in the nonextracted sample. PMID- 24222568 TI - Characterization of a glow discharge ion source for the mass spectrometric analysis of organic compounds. AB - A glow discharge ion source has been constructed for the mass spectrometric analysis of organic compounds. Characterization of the source has been made by studying the effect of pressure and discharge current on ionic distributions by anodic ion sampling along the discharge axis. Ion and electron densities and electronic temperatures have been calculated by using the single Langmuir probe technique to correlate the extraction efficiency with measured ion distributions and gain some insight into the ionization of organic molecules. The spectra obtained for several classes of organic compounds show that formation of parent molecular ions by proton transfer, resulting partly from the background water molecules, is a major low energy process while charge transfer, Penning ionization, and electron ionization ace probably responsible for the fragmentation observed. The spectra result from the simultaneous occurrence of high and low energy reactions, and their structural information content is very high, yielding both molecular and extensive fragment ion information. The glow discharge ion source has proved to be essentially maintenance-free, easy to operate, stable, and can be used at reasonable mass resolution (up to 70001. The source also provides picogram range detection limits and has a linear response range of about six orders of magnitude, which makes it an interesting ion source for routine analysis. Preliminary work conducted with chromatographic interfaces indicates that its use can be easily extended to both gas and liquid chromatography. PMID- 24222569 TI - Estimating probabilities of correct identification from results of mass spectral library searches. AB - This work presents a method for using mass spectral match factors reported by library search systems to obtain certain probabilistic indicators of correct identification. The overall probability that a retrieval is correct is formally separated into two independent terms. One of these is the probability that a retrieval is correct assuming that the correct match is contained in the library. This can be computed directly from test results. The other term represents the probability that the spectrum of the unknown compound is actually in the library. While the absolute value of this term cannot be computed, a relative value based solely on search results can be derived. This value may, if desired, be used to refine an initial estimate of the overall probability. Parameters used in this calculation are based on changes in test results caused by the logical removal of the test compounds from the library. These methods were parameterized from results of searching the MST/EPA/NIH Mass Spectral Database with 12,592 good quality replicate spectra and a simple mass spectral comparison function. The methodology should be equal1 applicable to other libraries and search systems. PMID- 24222570 TI - Gaseous myoglobin ions stored at greater than 300 K. AB - Multiply-charged myoglobin ions retaining the prosthetic heme group have been formed by electrospray, injected into a quadrupole ion trap, and stored for up to one second prior to mass analysis. Collisional activation experiments indicate that these ions readily fragment into the charged heme group and the complementary apomyoglobin ion. No fragmentation is observed, however, upon ion storage in the presence of a neutral bath gas at 1 * 10(-3) torr for up to one second. The significance of this observation is that these non-covalently-bound ions, in which both the heme group and the polypeptide carry charge, are kinetically stable for over one second at room temperature and, perhaps, at higher temperatures. This suggests that other biologically relevant ions derived using electrospray and bound by non-covalent interactions can be studied using the various tools available with ion storage mass spectrometers and by other techniques that employ relatively high pressure environments for the study of gaseous ions. PMID- 24222572 TI - alpha-crystallin modulates its chaperone activity by varying the exposed surface. AB - The alpha-crystallin family of small heat shock proteins possesses chaperone activity in response to stress and is involved in several neurological, muscular, and ophthalmic pathologies. This family includes the vertebrate lens protein alpha-crystallin, associated with cataract disease. In this study, by combining small-angle X-ray and light scattering techniques, the structure and shape of alpha-crystallin was revealed in its native state and after a transition caused by heat stress. Below critical temperature (Tc ), alpha-crystallin appears as an ellipsoid with a central cavity; whereas at high temperatures the cavity almost disappears, and the protein rearranges its structure, increasing the solvent exposed surface while retaining the ellipsoidal symmetry. Contextually, at Tc , alpha-crystallin chaperone binding shows an abrupt increase. By modelling the chaperone activity as the formation of a complex composed of alpha-crystallin and an aggregating substrate, it was demonstrated that the increase of alpha crystallin-exposed surface is directly responsible for its gain in chaperone functionality. PMID- 24222573 TI - Rounding frequency and hospital length of stay for children with respiratory illnesses: a simulation study. AB - BACKGROUND: Patient discharge from the hospital is linked to physician-led rounds, whereas discharge from the emergency department (ED) is more fluid. The relationship between rounding and length of stay (LOS) has not been quantitatively described. OBJECTIVES: To describe the arrival and discharge patterns in the ED and inpatient settings for children with respiratory illnesses and to explore how the timing and frequency of rounding could impact LOS. DESIGN/SETTING: Retrospective administrative data analyses of visits for respiratory illnesses to a tertiary care pediatric ED from May 2007 to April 2010. METHODS: ED visits for common respiratory conditions were selected based on International Classification of Diseases, 9th Revision, Clinical Modification codes, excluding complex comorbid conditions, severe illness, and intensive care unit admission. Discharge time was plotted against arrival time for the ED and inpatient unit. LOS was calculated. A Monte Carlo simulation model was developed to explore the influence of additional rounds on inpatient LOS. RESULTS: Of the 5503 included visits, 1285 (23.4%) resulted in inpatient care. Discharges from the ED typically occurred 2 to 5 hours after arrival, whereas most inpatient discharges occurred between 11 am and 6 pm regardless of admission time. Simulating 1 additional rounding session decreased predicted inpatient LOS by approximately 5 hours. CONCLUSIONS: In contrast to ED discharges that occurred around the clock, inpatient discharges for children with respiratory illnesses were concentrated during afternoon hours. Increasing rounding frequency may improve hospital efficiency but could result in unintended consequences such as fewer opportunities for patient education. PMID- 24222577 TI - Comparison of the reactivity of nonheme iron(IV)-oxo versus iron(IV)-imido complexes: which is the better oxidant? AB - Which is better? The first detailed comparison of the reactivity of nonheme iron(IV)-imido versus nonheme iron(IV)-oxo intermediates with substrates is presented. The iron(IV)-imido variant reacts with sulfides five times faster than iron(IV)-oxo, whereas the reverse trend is observed for hydrogen atom abstraction. These observed trends are analyzed and explained. PMID- 24222574 TI - Intraoperative fluorescence delineation of head and neck cancer with a fluorescent anti-epidermal growth factor receptor nanobody. AB - Intraoperative near-infrared (NIR) fluorescence imaging is a technology with high potential to provide the surgeon with real-time visualization of tumors during surgery. Our study explores the feasibility for clinical translation of an epidermal growth factor receptor (EGFR)-targeting nanobody for intraoperative imaging and resection of orthotopic tongue tumors and cervical lymph node metastases. The anti-EGFR nanobody 7D12 and the negative control nanobody R2 were conjugated to the NIR fluorophore IRDye800CW (7D12-800CW and R2-800CW). Orthotopic tongue tumors were induced in nude mice using the OSC-19-luc2-cGFP cell line. Tumor-bearing mice were injected with 25 ug 7D12-800CW, R2-800CW or 11 ug 800CW. Subsequently, other mice were injected with 50 or 75 ug of 7D12-800CW. The FLARE imaging system and the IVIS spectrum were used to identify, delineate and resect the primary tumor and cervical lymph node metastases. All tumors could be clearly identified using 7D12-800CW. A significantly higher tumor-to background ratio (TBR) was observed in mice injected with 7D12-800CW compared to mice injected with R2-800CW and 800CW. The highest average TBR (2.00 +/- 0.34 and 2.72 +/- 0.17 for FLARE and IVIS spectrum, respectively) was observed 24 hr after administration of the EGFR-specific nanobody. After injection of 75 ug 7D12-800CW cervical lymph node metastases could be clearly detected. Orthotopic tongue tumors and cervical lymph node metastases in a mouse model were clearly identified intraoperatively using a recently developed fluorescent EGFR-targeting nanobody. Translation of this approach to the clinic would potentially improve the rate of radical surgical resections. PMID- 24222578 TI - Superoxide disproportionation driven by zinc complexes with various steric and electrostatic properties. AB - Attractive models: Synthetic Zn(II) complexes were investigated as models of copper-zinc superoxide dismutase. Superoxide underwent a unique disproportionation reaction in the electrostatic sphere of the complexes (see picture; bpy=2,2'-bipyridyl). The effectiveness of the Zn(II) complexes in inducing the disproportionation of superoxide depended on both the Lewis acidity and the coordination geometry of the Zn center. PMID- 24222579 TI - Indole synthesis by rhodium(III)-catalyzed hydrazine-directed C-H activation: redox-neutral and traceless by N-N bond cleavage. AB - Fishing for complements! There is an alternative to the useful Fischer indole synthesis. The new method utilizes the same retrosynthetic disconnection but is based on a Rh(III) -catalyzed directed C?H activation step and a successive coupling with alkynes. PMID- 24222580 TI - Enhanced accuracy of single-molecule diffusion measurements with a photocleavable energy-transfer dyad. AB - A photocleavable energy-transfer dyad was synthesized, characterized, and applied to single-molecule fluorescence microscopy. After photocleavage, a combination of independent two-color single-molecule tracking and analysis of single-molecule energy-transfer efficiencies allows the determination of the temporal evolution of the relative distances between both fragments from the nm to the MUm scale. This gives access to a broad range of diffusion coefficients. PMID- 24222581 TI - Ammonia-in-oil-microemulsions and their application. AB - Liquid ammonia on the nanoscale: Ammonia-in-oil microemulsions are used to synthesize Bi, Re, CoN, and GaN nanoparticles, which can be obtained without further thermal treatment. These microemulsions are as reproducible and simple as their water-in-oil conterparts, with the exception of the required low temperature of -40 degrees C. PMID- 24222582 TI - Deletion of a dynamic surface loop improves stability and changes kinetic behavior of phosphatidylinositol-synthesizing Streptomyces phospholipase D. AB - Supplementary phosphatidylinositol (PI) was shown to improve lipid metabolism in animals, thus it is interesting for pharmaceutical and nutritional applications. Homogenous PI can be produced in transphosphatidylation of phosphatidylcholine (PC) with myo-inositol catalyzed by phospholipase D (PLD). Only bacterial enzymes able to catalyze PI synthesis are Streptomyces antibioticus PLD (SaPLD) variants, among which DYR (W187D/Y191Y/Y385R) has the best kinetic profile. Increase in PI yield is possible by providing excess of solvated myo-inositol, which is achievable at high temperatures due to its highly temperature-dependent solubility. However, high-temperature PI synthesis requires the thermostable PLD. Previous site-directed combinatorial mutagenesis at the residues of DYR having high B-factor yielded the most improved variant, D40H/T291Y DYR, obtained by the combination of two selected mutations. D40 and T291 are located within dynamic surface loops, D37-G45 (termed D40 loop) and G273-T313. Thus, in this work, thermostabilization of DYR SaPLD was attempted by rational design based on deletion of the D40 loop, generating two variants, Delta37-45 DYR and Delta38-46 DYR PLD. Delta38-46 DYR showed highest thermostability as its activity half-life at 70 degrees C proved 11.7 and 8.0 times longer than that of the DYR and Delta37 45 DYR, respectively. Studies on molecular dynamics predicted Delta38-46 DYR to have the least average RMSD change as temperature dramatically increases. At 60 and 70 degrees C, both mutants synthesized PI in a twofold higher yield compared to the DYR, while at the same time produced less of the hydrolytic side-product, phosphatidic acid. PMID- 24222583 TI - Doctors should be tried by a UK criminal court, not by the GMC. PMID- 24222584 TI - Young peoples' stigmatizing attitudes and beliefs about anorexia nervosa and muscle dysmorphia. AB - OBJECTIVE: The nature and extent of stigma toward individuals with anorexia nervosa and muscle dysmorphia remains underexplored. This study investigated attitudes and beliefs likely to be conducive to stigmatization of individuals with these conditions. METHOD: Male and female undergraduate students (n = 361) read one of four vignettes describing a fictional male or female character with anorexia nervosa or muscle dysmorphia, after which they responded to a series of questions addressing potentially stigmatizing attitudes and beliefs toward each character. RESULTS: Characters with anorexia nervosa were more stigmatized than characters with muscle dysmorphia, female characters were more stigmatized than male characters, and male participants were more stigmatizing than female participants. A large effect of character diagnosis on masculinity was observed, such that characters with anorexia nervosa were perceived as less masculine than characters with muscle dysmorphia, and this effect was more pronounced among male participants. However, no significant corresponding effects were observed for femininity. DISCUSSION: Females with anorexia nervosa may be particularly susceptible to stigmatization, especially by males. Anorexia nervosa and muscle dysmorphia are perceived as "female" and "male" disorders respectively, in line with societal gender role expectations, and this stigmatization is tied more strongly to perceptions of sufferers' masculinity than femininity. PMID- 24222586 TI - Editorial. PMID- 24222585 TI - Motivational antecedents of incident reporting: evidence from a survey of nurses and physicians. AB - QUESTIONS UNDER STUDY: Underreporting is a major issue when using incident reporting systems to improve safety in hospitals. Based on a psychological framework, this study investigated the motivational antecedents of the willingness to report into incident reporting systems in healthcare. Individual, organisational and system-related influences on the willingness to report incidents were investigated in a survey of physicians and nurses from five Swiss hospitals. METHODS: The motivational antecedents were tested using structural equation modelling. The sample consisted of 818 respondents, 546 nurses and 230 physicians; the response rate was 32%. The willingness to report was assessed by using a self-report scale, validated with the self-reported number of reported incidents during the previous year. RESULTS: The most important influence on the willingness to report was the transparency of the incident reporting system procedures to potential users, such as. knowing how and what kind of events to report. At the individual level, the perceived effectiveness of reporting was a relevant antecedent. At the organisational level, management support positively influenced the willingness to report. Different antecedents were found to be relevant for nurses and physicians. CONCLUSIONS: Implications are discussed that open up alternatives for the design and implementation of incident reporting systems in healthcare. For example, the results of the study point to opportunities for making incident reporting systems more transparent and participatory and to allow for experience of how they actually improve patient safety. PMID- 24222587 TI - The massachusetts institute of technology mass spectrometry school. AB - The events that led to the establishment of organic and biochemical mass spectrometry at MIT by the author in 1958, and its growth over the past three and one-half decades are briefly chronicled. A major emphasis is placed on the work with graduate students and postdoctoral researchers who were educated in the field and in turn further contributed to the training of others. An attempt is made at the construction of a genealogy encompassing - 7 to + 2 generations (the author representing 0). PMID- 24222588 TI - Collision-induced dissociation of uracil and its derivatives. AB - The collision-induced dissociation of protonated uracil has been studied by tandem mass spectrometry using models extensively labeled with stable isotopes, and derivatives of the kinds found in nucleic acids. Following collisional activation at 30 eV translational energy, protonated uracil dissociates through two principal pathways which do not occur in electron ionization mass spectra: (1) elimination of NH3 almost entirely from N-3, followed by loss of CO from C-4, 0(4); (2) loss of H2O, equally from 0(2) and 0(4). Elimination of HNCO, also the principal dissociation process from odd-electron molecular ions, proceeds primarily by loss of N-3, C-Z, O(2) and 10% from N-l, C-Z, 0(2). Several secondary dissociation products are formed with quantitative site specificity of skeletal atoms: C,HO+ (4-C0, C-5, C-6); H2CN+ (N-l, C-6); C2H2+ (N-l, C-5, C-6). First-step dissociation reactions are interpreted in terms of pyrimidine ring opening at likely sites of protonation after collisional activation of MH+. Collision-induced dissociation mass spectra of uracils with structural themes common to nucleic acids (methylation, replacement of 0 by S, C-5 substitution) follow analogous reaction paths which permit assignment of sites of substitution, and exhibit ion abundance changes attributed to differences in substituent basicity and electron density. PMID- 24222589 TI - Characterization of protein iv-glycosylation by reversed-phase microbore liquid chromatography / electrospray mass spectrometry, complementary mobile phases, and sequential exoglycosidase digestion. AB - A strategy for the identification of the site occupancy and glycoform heterogeneity, including sialylation occurring at specific sites of N-linked giycoproteins is presented using the asparagine-linked glycosylation on bovine fetuin for illustration. This is achieved by microbore high-performance liquid chromatography/electrospray ionization mass analysis (LC/ESIMS) of the tryptic glycopeptide mixtures with an acetonitrile-based mobile phase followed by sequential steps of residue (and linkage) specific glycoform degradation and LC/ESIMS analysis at each stage. In addition, chromatographic separation of the site-specific glycoforms of tryptic glycopeptides is accomplished by the use of an alternative, mass spectrometrically compatible mobile phase water/ethanol/propanol/formic acid. By employing this nontraditional mobile phase for characterizing the complete tryptic digest, and using highly specific exoglycosidases in combination with LC/ESIMS analysis, a previously uncharacterized carbohydrate (a disialo biantennary complex oligosaccharide) was identified as a novel structure at Asn(81) of bovine fetuin. (J Am Sot Mass Spectrom 1994, 5, 350-358). PMID- 24222590 TI - Quantitative assessment of cysteine and cystine in peptides and proteins following organomercurial derivatization and analysis by matrix-assisted laser desorption ionization mass spectrometry. AB - Protocols for the analysis of the sulfhydryl content in peptides and proteins using chemical derivatization by organomercurial reagents and analysis by matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) have been developed. The number of reactive cysteine residues in peptides and proteins can be determined by exploiting the affinity and selectivity of organomercurial reagents for macromolecular thiols. Mass shifts observed in MALDI mass spectra obtained before and after cysteine derivatization with p-hydroxy-mercuribenzoate (pHMB) permit the number of free sulfhydryl groups to be determined. The pHMB derivative of each free cysteine residue provides a mass shift of 321 u, overcoming limitations in the mass resolution of MALDI time-of-flight mass spectrometry. Reactive cysteine residues in a macromolecule can be selectively derivatized by using a fivefold molar excess of pHMB reagent. Total sulfhydryl content (i.e., cysteine and cystine) can be determined after disulfide reduction. However, analyses for total cysteine content are more complex, requiring protein denaturation, cystine reduction, and sample purification before derivatization and analysis by MALDI-MS. Conditions for sample denaturation, alkyl-phosphine reduction, pHMB derivatization, and sample purification by analyte adsorption and desalting on protein transfer membranes, are described for cysteine/cystine analysis performed on microgram (10-200 pmol) quantities of somatostatin, insulin, hemoglobin, and beta-lactoglobulin. PMID- 24222591 TI - A comparison of the reactions of the oxide radical anion (o(-.)) with simple aromatic compounds at atmospheric and at reduced pressure conditions. AB - The reactions of oxide radical anions (O(-.)) with benzene and toluene under atmospheric pressure (APCI) and conventional chemical ionization (CI) conditions were compared. Hydrogen radical (H(-)) displacement by oxygen, yielding [M - H + O](-), was observed in both the APCI and the CI source. However, the product, [M 2H](-.), derived from dihydrogen radical ion (H2 (+.)) transfer which was observed in the CI spectra, was consistently absent under APCI conditions. This behavior is rationalized in terms of the higher pressures and chemical equilibrium associated with the APCI source. In addition to the formation of the a priori expected phenoxide isomers, the reaction of O(-.) with toluene to yield the [M - H + O](-) product generates a benzyloxide anion. Tandem mass spectrometry data from collision-induced dissociation and isotopic labeling with deuterium support a reaction mechanism initiated by alpha hydrogen abstraction for both the H(.) and the H2 (+.) transfer pathways. PMID- 24222592 TI - Characterization of an opioid peptide-containing protein and of bovine alpha lactalbumin by electrospray ionization and liquid secondary ion mass spectrometry. AB - Mass spectrometry methods have been used to characterize two proteins: an opioid peptide-containing protein extracted from bovine pituitary, and bovine alpha lactalbumin (BAL). A protein that contains beta-endorphin was found in bovine pituitary, and that protein was characterized with electrospray ionization mass spectrometry (ESIMS), gel permeation chromatography, reversed-phase high performance liquid chromatography (RP-HPLC), radioimmunoassay, trypsinolysis, and liquid secondary ion mass spectrometry (LSIMS).BAL is a protein that was used as a model to develop analytical methods to study opioid peptide-containing proteins. Commercial BAL was purified by RP-HPLC, and its molecular weight (M.W.) was determined by ESIMS. The shift in mass observed following dithiothreitol (DTT) reduction estimated the number of disulfide bonds.For all of the data obtained for BAL with or without RP-HPLC separation, ESIMS determined the M.W. of the peptides produced by trypsin treatment of BAL, and LSIMS selected a precursor ion, the protonated molecule ion [M + H](+), of a tryptic peptide, which was analyzed by tandem mass spectrometry. Following DTT reduction, ESIMS and LSIMS detected each peptide that contained disulfide bonds in that mixture of tryptic peptides. PMID- 24222593 TI - Nitrogen isotopic analyses by isotope-ratio-monitoring gas chromatography / mass spectrometry. AB - Amino acids containing natural-abundance levels of (15)N were derivatized and analyzed isotopically using a technique in which individual compounds are separated by gas chromatography, combusted on-line, and the product stream sent directly to an isotope-ratio mass spectrometer. For samples of N2 gas, standard deviations of ratio measurement were better than 0.10/00 (Units for delta are parts per thousand or per million (0/00).) for samples larger than 400 pmol and better than 0.50/00 for samples larger than 25 pmol (0.10/00 (15)N is equivalent to 0.00004 atom % (15)N). Results duplicated those of conventional, batchwise analyses to within 0.050/00. For combustion of organic compounds yielding CO2/N2 ratios between 14 and 28, in particular for N-acetyl n-propyl derivatives of amino acids, delta values were within 0.250/00 of results obtained using conventional techniques and standard deviations were better than 0.350/00. Pooled data for measurements of all amino acids produced an accuracy and precision of 0.04 and 0.230/00, respectively, when 2 mnol of each amino acid was injected on column and 20% of the stream of combustion products was delivered to the mass spectrometer. PMID- 24222594 TI - A low voltage ion transport system for external ionization fourier transform mass spectrometry. AB - An efficient ion transport system that interfaces external ion sources with a commercial dual-cell Fourier transform mass spectrometry (FTMS) system so as to retain maximum experimental flexibility has been constructed. Electrostatic lenses were used for ion transfer with potentials less than 200 V to preclude discharges. Spectra were recorded by thermal ionization and by electrospray ionization. Other high pressure ionization methods can be easily added to the external ion source chamber, making this a general solution for ion transport into an FTMS system. The efficiency of ion transfer was measured to be approximately 30%. A pressure ratio of 10(5) between the external ion source chamber and the second cell has been demonstrated. The system incorporates a computer-controlled gate valve to isolate the cell regions from the external ion source chamber, permitting optimal conditions for ion injection and accumulation, and then after closing the valve, recording spectra at low pressure with high resolution. Spectra of Gramicidin S (resolution 90,000 at m/z 1164), aprotinin (resolution 410,000 at m/z 1304), and horse heart cytochrome c (resolution 50,000 at m/z 1546) are shown. PMID- 24222595 TI - Effect of tautomerization on the fast-atom bombardment tandem mass spectra of azo dyes. AB - The effect of tautomerization on the collision-induced dissociation of negative ions produced from sulfonated azo dyes by fast-atom bombardment (FAB) was studied by analyzing the product ion spectra of several related compounds. The mechanisms by which azo dyes fragment were found to depend on the formation and stability of tautomers. The extent of tautomerization was affected by the number and location of hydroxy groups on the dye, as well as by the FAB matrix. Ions that retained a sodium were often inhibited from forming tautomers and gave different product ions. Substitution of deuterium for hydrogen on the hydroxy groups aided in the identification of ions having more than one possible structure and provided verification of proposed mechanisms. Mechanisms involving ions retaining a sodium were verified by substituting potassium for the sodium. PMID- 24222596 TI - Analysis of long-chain fatty acyl coenzyme a thioesters by negative ion fast-atom bombardment mass spectrometry and tandem mass spectrometry. AB - Long-chain acyl Coenzyme A (CoA) is essentially composed of three major chemical groups, fatty acyl-, phosphopantetheino-, and 3', 5',-adenosine diphospho moieties. The negative ion fast-atom bombardment mass spectrometry spectra of long-chain acyl CoA thioesters were characterized by the formation of abundant [M - H](-) and two distinct classes of fragment ions, one class which retained the acyl group and another class which is related to CoA that contains the phosphopantethene and adenine. The ions which retained the acyl group in the spectrum of palmitoyl CoA appeared at m/z 675, 657, 595, and 577 and were found to decompose by loss of alkylketene observed at m/z 357 and 339. Those ions which retained the adenine group were observed at m/z 426 and 408. In contrast to these ions observed following fast-atom bombardment ionization, tandem mass spectrometry of the [M - H](-), from palmitoyl CoA (m/z 1004), yielded the adenine-containing ions as major products and the acyl-containing ions were of low abundance or not detected. These results suggested that the formation of many characteristic ions observed in direct FAB analysis occurred during the desorption process. The unique relationship between ions which involved the transition from acyl-containing ions to only CoA-containing ions by the loss of alkylketene allowed the development of tandem mass spectrometry protocols for the analysis of acyl CoA mixtures. Precursor scans of either m/z 357 or 339 yielded the identification of each species in a complex mixture. Identification of specific species was obtained with a neutral loss scan of the mass for a specific alkylketene. PMID- 24222597 TI - The mass spectrometry of helical unfolding in peptides. AB - Two model peptides, melittin and a growth hormone releasing factor (GRF) analog, have been studied by mass spectrometry and tandem mass spectrometry during the course of their deuterium exchange. Both peptides are known from previous work to form alpha-helices in solution. When the peptides are exposed to deuterated solvents, their masses increase as deuterium atoms replace protons in the exchangeable sites of the peptides. The mass spectrometry results clearly indicate multiple populations of exchangeable protons: Some exchange very fast, and are presumably on the surface and not involved in hydrogen bonding; others exchange much more slowly, indicating that they are probably participating in hydrogen bonding.Tandem mass spectrometric experiments were conducted, and the masses of the product (fragment) ions were used to determine where in the peptide the deuterium atoms were incorporated. The results agree very well with NMR studies of the same peptides. Melittin appears as two helical segments with a kink around Pro-14. The GRF analog contains a single long helix, spanning almost the entire length of the peptide. The dynamics of the unfolding of the helices can also be explored by observing how the exchange progresses with time. PMID- 24222598 TI - Gas phase hydrogen / deuterium exchange in electrospray ionization mass spectrometry as a practical tool for structure elucidation. AB - Two methods for gas phase hydrogen/deuterium exchange have been developed for the analysis of small molecules. Hydrogen/deuterium exchange has been implemented by making simple modifications to the plumbing for the nebulizer and curtain gases on a nebulization-assisted electrospray ion source. The nebulizer gas exchange method has demonstrated deuterium exchange levels of 84-97% for a variety of molecules representing a wide range of structural classes containing up to 51 potentially exchangeable hydrogens; this allowed determination of the number of exchangeable hydrogens for all of the molecules studied containing <= 25 labile hydrogens (M r <= 3000). ND3 gas consumption is minimized in the nebulizer method by toggling the nebulizer from air to ND3 for only a few scans of the total sample elution period. The curtain gas exchange method is more variable, yielding exchange levels of 32-98% for the same set of molecules; this was still sufficient to allow determination of > 70% of the molecules studied containing <= 25 labile hydrogens. Gas consumption is minimized in the curtain method by replacing <= 10% of the curtain gas flow with ND3. Neither the nebulizer nor curtain exchange method requires the use of deuterated or aprotic solvents at typical 2 MUL/min flow rates. PMID- 24222599 TI - Mass spectrometric characterization of a series of adenosylated peptides acting as bisubstrate analogs of protein kinases. AB - We are currently developing strategies to synthesize bisubstrate analogs as potential inhibitors of serine and tyrosine protein kinases; several such analogs have been synthesized. The initial target proteins were the cAMP dependent protein kinase (cAPK) and the Ca(+2)/calmodulin dependent protein kinase (CaM kiiase II). These bisubstrate analogs were based on either known peptide substrates such as kemptide, a seven amino acid peptide substrate of cAPK, or on inhibitory peptides such as a seventeen amino acid peptide encompassing the autoinhibitory domain of CaM kinase II. Peptides containing a single phosphoserine group were first synthesized and then adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), or adenosine 5'-triphosphate (ATP) was coupled through the serine phosphate with prior activation by 1,1 carbonyldiimidazole using either a solution or solid phase reaction scheme. In this current study, we report the characterization of the bisubstrate analogs by liquid secondary ionization mass spectrometry (LSIMS), matrix-assisted laser desorption mass spectrometry (MALDI), and tandem mass spectrometry (MS/MS).In the positive-ion mode, the LSIMS spectra of the bisubstrate analogs yielded a series of molecular ions containing mono-, di-, and trivalent cation adducts. Cation adducts were absent in the negative-ion mode where the dominant species were deprotonated molecular ions, [M - H](-), making this latter technique more useful for confirming product identity and assessing purity. Analysis of these compounds by MALDI in both the positive- and negative-ion modes yielded molecular ions which also contained metal ion adducts, although they were limited primarily to Fe(+2) adducts. Unlike LSIMS, the MALDI spectra showed no evidence for the elimination of the phosphoadenosine or other structural moieties. When these compounds were subjected to high energy collision-induced dissociation (CID), the dominant fragmentation pathways under positive-ion MS/MS conditions resulted from cleavage of the phosphate linkages to the adenosine moiety with charge retention on the peptide, although a major peak for 5'-deoxyadenosine was also seen at m/z 250. Charge retention in the negative-ion mode was most pronounced for ion fragments containing the highly acidic phosphate moieties and yielded phosphoadenosine related ions, for example, (AMP-H)(-), (AMP-H-H2O)(-), (ADP-H)( ), etc., as well as ions originating from the phosphate linker such as PO3 (-), H2PO4 (-), HP2O6 (-), H3P2O7 (-), and H2P3O9 (-). The largest phosphoadenosine ion in the negative-ion CID spectra for each bisubstrate analog, for example, m/z 426 (ADP-H)(-), m/z 506 (ATP-H)(-), or m/z 586 (AP4-H)(-), indicated that the desired covalent modification had been formed between the phosphoserine and APn moieties. PMID- 24222600 TI - Chiral recognition in the gas phase: Mass spectrometric studies of diastereomeric cobalt complexes. AB - Results of mass analyzed ion kinetic energy (MIKE) spectra and kinetic energy release (KER) measurements of diastereomeric octahedral cobalt complexes indicate that these diastereomers can be distinguished in the gas phase. Four alkyl tartrate esters were complexed to cobalt trisacetylacetonate (Co(acac)3) in the presence of a chiral auxiliary, RR- and SS-threohydrobenzoin. Different KER values of the product ion generated from [Co(acac)2/D- or L-diisopropyl tartrate](+) reflect differences in the precursor ion structure. The dissociation pathway resulting in this product ion is believed to arise via a hydride transfer from the acetylacetonate ligand to the metal center with subsequent loss of neutral organic species. It has been established that two conditions are necessary for observation of chiral recognition in this system; (1) the cobalt complex must be octahedral and (2) a chemical kinetic resolving agent must be present during formation of the complex. PMID- 24222601 TI - Enhancement of ion transmission at low collision energies via modifications to the interface region of a spectrometer. AB - The transmission efficiency of precursor and product ions decreases significantly at lower collision energies in a four-sector tandem mass spectrometer. In an effort to improve the overall ion transmission in this energy regime three modifications were made in the interface region between the two stages of mass analysis. An einzel lens was inserted prior to the deceleration lens of the collision cell block to reduce the precursor ion beam diameter. The collision cel1 block was reduced in thickness while maintaining the collision path length, thus increasing the number of ions which entered and exited the gas chamber, while removing any stray electrical fields. Finally, a second active focusing element was incorporated after the collision cell block to enhance the collection efficiency of the product ions. A tandem mass spectrum of angiotensin I obtained with this interface, at a collision cell block potential of 9200 volts, exhibited classical high energy collision-induced dissociation (CID) fragmentation patterns, a precursor ion transmission of 92% and an overall CID efficiency of approximately 7.5%. These improvements have resulted in a dramatically higher overall ion transmission at high collision cell potentials as well as sufficient sensitivity in acquiring good quality CID spectra in the lower collision energy regime (i.e., 60 eV). (460-469). PMID- 24222603 TI - The 42nd ASMS Conference on Mass Spectrometry May 29 - June 3, 1994 Hyatt Regency Hotel, Chicago, Illinois Preliminary Program. PMID- 24222604 TI - Biosynthesis and mass spectrometric imaging of tolaasin, the virulence factor of brown blotch mushroom disease. PMID- 24222605 TI - Overweight and obesity associated with increased total serum calcium level: comparison of cross-sectional data in the health screening for teaching faculty. AB - Obesity is a risk of cardiovascular diseases. Our previous studies revealed that serum calcium level may have influence in the blood pressure to older male subjects. The aim of this study was to evaluate the relationship between total serum calcium level and overweight and obesity subjects. In our study, overweight and obesity status and total serum calcium level were measured among 2,503 subjects, at age range of 22-94 years, who were recruited for the routine health screening in 2006. The estimated mean for age (p < 0.001), white blood cell count (p = 0.037), hemoglobin concentration (p < 0.001), red blood cell count (p < 0.001), total serum calcium level (p < 0.001), total cholesterol weight (p < 0.001), HDL-cholesterol (p < 0.001), LDL-cholesterol (p < 0.001), and triglyceride (p < 0.001) of overweight and obesity subjects were significantly higher than those of non-overweight subjects. The prevalence of overweight/obesity in subjects according to the log-transformed total serum calcium level quartiles was 16.3-30.5 %. The prevalence of overweight/obesity subjects showed trends that were significant according to the total serum calcium level quartiles (p < 0.001). The odds ratios (ORs) and 95 % confidence intervals (CIs) for overweight/obesity of the second, third, and fourth quartiles compared to the lowest quartile were 1.407 (1.050-1.883), 1.543 (1.136-2.095), and 1.360 (0.995-1.859), respectively, after adjusting for sex and age (p < 0.001). These findings suggest that a higher prevalence of adult overweight/obesity is weakly associated with higher total serum calcium level in the Chinese population. PMID- 24222606 TI - Blood metals concentration in type 1 and type 2 diabetics. AB - Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n = 192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n = 68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n = 59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92-101 % of certified values. Type 1 diabetes was found to be associated with Cr (p = 0.02), Mn (p < 0.001), Ni (p < 0.001), Pb (p = 0.02), and Zn (p < 0.001) deficiency, and type 2 diabetes with Cr (p = 0.014), Mn (p < 0.001), and Ni (p < 0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p < 0.001, rho = 0.400) and Pb and BMI (p < 0.001, rho = 0.309), while a negative correlation between Fe and age (p = 0.002, rho = -0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p = 0.017, rho = -0.294) and Fe and BMI (p = 0.026, rho = -0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects. PMID- 24222607 TI - Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis. AB - Platelet aggregation-inducing factor Aggrus, also known as podoplanin, is associated with tumor malignancy by promoting hematogenous metastasis. Aggrus overexpression has been reported in some tumor tissues including lung, esophagus, head and neck and brain. We here found the frequent upregulation of aggrus mRNA in urinary bladder cancers using cancer tissue panels from various organs. Immunohistochemical analysis confirmed Aggrus protein expression in urinary bladder cancers and suggested a positive correlation between Aggrus expression and metastatic tendency in bladder cancers. Endogenous expression of Aggrus protein on the cell surface was found in the mouse bladder cancer MBT-2 cell line and human bladder cancer SCaBER cell lines. Knockdown of Aggrus expression in MBT 2 cells decreased their ability to induce platelet aggregation and form pulmonary metastasis in syngeneic mouse models. Knockdown of Aggrus expression in the human bladder cancer SCaBER cells also attenuated their ability to induce platelet aggregation and form pulmonary metastasis in mice. Moreover, pulmonary metastasis of SCaBER cells was prevented by prior administration of our generated anti Aggrus neutralizing monoclonal antibodies by attenuating their retention in lung. These results indicate that Aggrus plays an important role in bladder cancer metastasis. Thus, anti-Aggrus neutralizing antibodies would be useful for the prevention of hematogenous metastasis of Aggrus-positive bladder cancer. PMID- 24222608 TI - Breakthrough bacteremia by linezolid-susceptible Enterococcus faecalis under linezolid treatment in a severe polytrauma patient. PMID- 24222609 TI - Reply to "Breakthrough bacteremia by linezolid-susceptible Enterococcus faecalis under linezolid treatment in a severe polytrauma patient". PMID- 24222611 TI - Treatment challenges associated with bone echinococcosis. AB - OBJECTIVES: In this literature review, we concentrate on epidemiology and therapy of osseous echinococcosis, with an emphasis on the recurrence risk. METHODS: Literature review 1930-2012. RESULTS: We retrieved 200 publications based upon single case reports or case series, mostly from resource-poor settings. Among the 721 rural patients (22% females; median age 37 years), 60% of all reported cases were from the Mediterranean region and almost all patients were immune competent. Echinococcus granulosus was identified as the most frequent species. Most infections involved a single bone (602/721; 83%) and often the spine (321 cases; 45%). In eight cases (8/702; 1%), a secondary bacterial surgical site infection was reported. Surgical intervention was performed in 702 cases (97%), with single intervention in 687 episodes (95%). Complete excision of the lesion was possible in only 117 episodes (16%). Albendazole was by far the most frequently used agent in monotherapy with various dosages, while mebendazole in monotherapy was less frequent (32 cases). The median duration of antihelminthic therapy was 6 months (range 0.7-144 months). There were 124 recurrences (17%) after a median delay of 2 years (range 0.4-17 years). In multivariate analysis, the presence of visceral organ involvement increased the odds of recurrence by 5.4 (95% CI 3.1-9.4), whereas the number of surgical interventions, the duration of antihelminthic therapy or the use of hypertonic saline did not influence recurrence. CONCLUSIONS: Bone echinococcosis is a rare parasitic disease. While treatment modalities vary considerably, combined surgical and medical approaches are the standard of care with a 17% risk of recurrence. PMID- 24222612 TI - A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking. AB - OBJECTIVES: To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. METHODS: The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed days and per 100 bed-days/age-adjusted comorbidity score. RESULTS: Results showed that antibiotic use had significant positive relationships with the sum of age adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. CONCLUSIONS: The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects. PMID- 24222613 TI - GM-CSF knockout mice for preclinical testing of agents with antimicrobial activity against Mycobacterium abscessus. AB - OBJECTIVES: Of the non-tuberculous mycobacteria, Mycobacterium abscessus is particularly refractory to antimicrobial therapy and new agents with activity against these pathogens are urgently needed. The screening of candidate antimicrobial agents against M. abscessus requires a relevant and reproducible animal model of chronic infection. Granulocyte-macrophage colony-stimulating factor knockout (GM-CSF KO) mice were used to develop a new animal model of chronic pulmonary M. abscessus infection that can be used for preclinical efficacy testing of antimicrobial drugs. METHODS: GM-CSF KO mice were infected with a clinical isolate of M. abscessus via intrapulmonary aerosol delivery using a microsprayer device. The clinical condition, histology and cfu of M. abscessus infected GM-CSF KO mice were evaluated over a period of 4 months. Mice were treated with azithromycin (100 mg/kg) by oral gavage and the clinical condition, histology and bacterial burden was determined after 2 weeks of treatment. RESULTS: We show that pulmonary infection of GM-CSF KO mice with M. abscessus results in a chronic pulmonary infection that lends itself to preclinical testing of new antimicrobial drugs against this bacterium. Azithromycin treatment of M. abscessus-infected GM-CSF KO mice resulted in a lower bacterial burden in the lungs and spleen, weight gain and significant improvement in lung pathology. CONCLUSIONS: Intrapulmonary aerosol infection of GM-CSF KO mice with M. abscessus is a useful animal model for studying pathogenesis as well as pre-clinical testing of new compounds against M. abscessus in acute or chronic phases of infection. PMID- 24222614 TI - Site-specific engineering of chemical functionalities on the surface of live hepatitis D virus. PMID- 24222615 TI - Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity. AB - Streptococcus suis is an important cause of different pathologies in pigs and humans, most importantly fibrinosuppurative meningitis. Tissue infected with this pathogen is substantially infiltrated with neutrophils, but the function of neutrophil extracellular traps (NETs) - a more recently discovered antimicrobial strategy of neutrophils - in host defence against Strep. suis has not been investigated. The objective of this work was to investigate the interaction of Strep. suis with NETs in vitro. Strep. suis induced NET formation in porcine neutrophils and was entrapped but not killed by those NETs. As the amount of NETs decreased over time, we hypothesized that a known extracellular DNase of Strep. suis degrades NETs. Though this nuclease was originally designated Strep. suis secreted nuclease A (SsnA), this work demonstrated surface association in accordance with an LPXTG cell wall anchor motif and partial release into the supernatant. Confirming our hypothesis, an isogenic ssnA mutant was significantly attenuated in NET degradation and in protection against the antimicrobial activity of NETs as determined in assays with phorbol myristate acetate (PMA) stimulated human neutrophils. Though assays with PMA-stimulated porcine neutrophils suggested that SsnA also degrades porcine NETs, phenotypic differences between wt and the isogenic ssnA mutant were less distinct. As SsnA expression was crucial for neither growth in vitro nor for survival in porcine or human blood, the results indicated that SsnA is the first specific NET evasion factor to be identified in Strep. suis. PMID- 24222616 TI - Surface proteins of group G Streptococcus in different phases of growth: patterns of production and implications for the host-bacteria relationship. AB - Group G Streptococcus (GGS) is a human bacterial pathogen expressing surface proteins FOG and protein G (PG) which interact with several host defence systems, including the complement and contact systems. Selected reaction monitoring mass spectrometry, electron microscopy and protein binding assays were used to track the amounts of FOG and PG intracellularly and on the bacterial surface during different phases of growth. Large and increasing amounts of PG were present on the surface in the stationary growth phase, and this was due to de novo production. In contrast, the amount of FOG did not change substantially during this phase. Apart from PG, a number of housekeeping proteins also increased in abundance in the stationary phase. These results show that GGS protein production is active during the stationary phase and that the bacteria actively remodel their surface and enter a less pro-inflammatory state in this phase. PMID- 24222617 TI - Temperature-dependence of yadBC phenotypes in Yersinia pestis. AB - YadB and YadC are putative trimeric autotransporters present only in the plague bacterium Yersinia pestis and its evolutionary predecessor, Yersinia pseudotuberculosis. Previously, yadBC was found to promote invasion of epithelioid cells by Y. pestis grown at 37 degrees C. In this study, we found that yadBC also promotes uptake of 37 degrees C-grown Y. pestis by mouse monocyte/macrophage cells. We tested whether yadBC might be required for lethality of the systemic stage of plague in which the bacteria would be pre adapted to mammalian body temperature before colonizing internal organs and found no requirement for early colonization or growth over 3 days. We tested the hypothesis that YadB and YadC function on ambient temperature-grown Y. pestis in the flea vector or soon after infection of the dermis in bubonic plague. We found that yadBC did not promote uptake by monocyte/macrophage cells if the bacteria were grown at 28 degrees C, nor was there a role of yadBC in colonization of fleas by Y. pestis grown at 21 degrees C. However, the presence of yadBC did promote recoverability of the bacteria from infected skin for 28 degrees C-grown Y. pestis. Furthermore, the gene for the proinflammatory chemokine CXCL1 was upregulated in expression if the infecting Y. pestis lacked yadBC but not if yadBC was present. Also, yadBC was not required for recoverability if the bacteria were grown at 37 degrees C. These findings imply that thermally induced virulence properties dominate over effects of yadBC during plague but that yadBC has a unique function early after transmission of Y. pestis to skin. PMID- 24222618 TI - Expression of a bacterial catalase in a strictly anaerobic methanogen significantly increases tolerance to hydrogen peroxide but not oxygen. AB - Haem-dependent catalase is an antioxidant enzyme that degrades H2O2, producing H2O and O2, and is common in aerobes. Catalase is present in some strictly anaerobic methane-producing archaea (methanogens), but the importance of catalase to the antioxidant system of methanogens is poorly understood. We report here that a survey of the sequenced genomes of methanogens revealed that the majority of species lack genes encoding catalase. Moreover, Methanosarcina acetivorans is a methanogen capable of synthesizing haem and encodes haem-dependent catalase in its genome; yet, Methanosarcina acetivorans cells lack detectable catalase activity. However, inducible expression of the haem-dependent catalase from Escherichia coli (EcKatG) in the chromosome of Methanosarcina acetivorans resulted in a 100-fold increase in the endogenous catalase activity compared with uninduced cells. The increased catalase activity conferred a 10-fold increase in the resistance of EcKatG-induced cells to H2O2 compared with uninduced cells. The EcKatG-induced cells were also able to grow when exposed to levels of H2O2 that inhibited or killed uninduced cells. However, despite the significant increase in catalase activity, growth studies revealed that EcKatG-induced cells did not exhibit increased tolerance to O2 compared with uninduced cells. These results support the lack of catalase in the majority of methanogens, since methanogens are more likely to encounter O2 rather than high concentrations of H2O2 in the natural environment. Catalase appears to be a minor component of the antioxidant system in methanogens, even those that are aerotolerant, including Methanosarcina acetivorans. Importantly, the experimental approach used here demonstrated the feasibility of engineering beneficial traits, such as H2O2 tolerance, in methanogens. PMID- 24222619 TI - Microfluidic perfusion culture of human induced pluripotent stem cells under fully defined culture conditions. AB - Human induced pluripotent stem cells (hiPSCs) are a promising cell source for drug screening. For this application, self-renewal or differentiation of the cells is required, and undefined factors in the culture conditions are not desirable. Microfluidic perfusion culture allows the production of small volume cultures with precisely controlled microenvironments, and is applicable to high throughput cellular environment screening. Here, we developed a microfluidic perfusion culture system for hiPSCs that uses a microchamber array chip under defined extracellular matrix (ECM) and culture medium conditions. By screening various ECMs we determined that fibronectin and laminin are appropriate for microfluidic devices made out of the most popular material, polydimethylsiloxane (PDMS). We found that the growth rate of hiPSCs under pressure-driven perfusion culture conditions was higher than under static culture conditions in the microchamber array. We applied our new system to self-renewal and differentiation cultures of hiPSCs, and immunocytochemical analysis showed that the state of the hiPSCs was successfully controlled. The effects of three antitumor drugs on hiPSCs were comparable between microchamber array and 96-well plates. We believe that our system will be a platform technology for future large-scale screening of fully defined conditions for differentiation cultures on integrated microfluidic devices. PMID- 24222620 TI - Insertion reactions of metal carbonyl anions with methyl formate in the gas phase as revealed by (13)C- and D-labeling. AB - School of Chemistry, University of New South Wales, Kensington, Australia Institute of Mass Spectrometry, University of Amsterdam, Nieuwe Achtergracht The gas-phase reactions of coordinatively unsaturated metal carbonyl anions (M(CO) n (-) , M=Cr, Mn, Fe, Co; n=0-3 and Co(CO)nNO(-), n=0-2) with unlabeled and D- and (13)C-labeled methyl formate have been studied with Fourier transform ion cyclotron resonance mass spectrometry. The reactions proceed in most instances by loss of one or more CO molecules from the collision complex. In the reactions of the dicarbonyl and tricarbonyl anions with H(13)COOCH3, part of the eliminated carbon monoxide molecules contain the label revealing the occurrence of initial insertion of the metal center into the bonds adjacent to the carbonyl function of the substrate with formation of five- or six-coordinate intermediates, respectively. In addition, the MnCCO) 3 (-) , Fe(CO) 2 (-) , and CoCCO) 2 (-) ions react by the loss of methanol and a [C,H2,O] neutral species. The D- and (13)C-labeling show that methanol is expelled in a reductive elimination from a five- or six-coordinate species, whereas the [C,H2,O] loss is a more complex process possibly involving the competing losses of formaldehyde and CO + H2. In the reaction of Fe(CO) 3 (-) with H 13 (13) COOCH3, a facile consecutive exchange of all three CO ligands of the reactant ion for (13)CO is observed. This novel reaction appears to involve initial insertion into the H(13)CO-OCH3-bond followed by facile hydrogen shifts from the formyl ligand to a CO Hgand prior to the loss of unlabeled methyl formate. PMID- 24222621 TI - Metastable and collision-induced fragmentation studies of all C4H 12Si (+) isomers; a systematic study of structure-reactivity relations. AB - Metastable ion (MI) and collision-induced dissociation (CID) mass spectra have been recorded and compared for all nine C4H12Si(+.) isomers. The (Me)4Si(+.), t BuSiH 3 (+.) , s-BuSiH 3 (+) , and (Me)2EtSiH(+.) isomers have unique MI and CID mass spectra. The MI mass spectra, including the kinetic energy release values, of (Me)(i-Pr)SiH 2 (+.) and (Me)(n-Pr)SiH 2 (+.) are identical, which implies isomerization. MI data also suggest that a fraction of the n-BuSiH 3 (+.) ions rearrange into branched (Me)2EtSiH(+.) ions and a fraction of the n-BuSiH 3 (+.) ions rearrange into branched s-BuSiH 3 (+.) ions. A comparison with the isomeric C5H 12 (+.) pentanes reveals a crucial difference: H2 loss occurs for n-BuSiH 3 (+.) , i-BuSiH 3 (+.) , s-BuSiH 3 (+.) , (Me)(n-Pr)SiH 2 (+.) , (Me)(i-Pr)SiH 2 (+.) , and Et2SiH 2 (+.) , but not for any of the C5Hi 12 (+.) isomers. Generation of four- or five-membered silicon containing rings is suggested for H2 loss from the C4H12Si(+.) silanes. PMID- 24222622 TI - APCI low energy collision-induced dissociation fragmentation of protonated ortho silicates: mclafferty or ion-neutral complex rearrangement? AB - The fragmentation mechanism of tetraethyl ortho silicate and tetrapropyl ortho silicate was studied to determine if the consecutive alkene losses observed in their MS/MS daughter ion spectra were produced via a McLafferty rearrangement or by ion-neutral rearrangement mechanisms. The experiments were carried out using atmospheric pressure chemical ionization and low energy collision-induced dissociation. Deuterium labeling of the gamma-position provided evidence mat the rearrangement mechanism of the successive alkene losses proceeds predominantly via the ion-neutral complex mechanism. Because the energies imparted to the ions in this experiment are of the same order of magnitude as solution phase reactions, this mechanism may shed light on the formation of silica gels (e.g., aerogels) in that similar structures have been proposed as reaction intermediates in the polymerization of SiO2. PMID- 24222623 TI - O(-) and OH(-) chemical ionization of some fatty acid methyl esters and triacylglycerols. AB - O(-) and OH(-) react with fatty acid methyl esters (FAMES) under chemical ionization conditions both as Bronsted bases to form [M - H](-) and as nucleophiles to form the carboxylate ion RCOO(-). O(-) shows a much greater tendency to react as a nucleophile than does OH(-). The [M - H](-) ions fragment by elimination of CH(3)OH, with unsaturation in certain positions in the fatty acid hydrocarbon chain promoting this elimination for unknown reasons. The reaction of O(-) and OH(-) with triacylglycerols leads to [M - H](-), characteristic of the molecular mass, and to carboxylate ions characteristic of the fatty acid(s) present in the lipid. The presence of the three ester functions in the lipids greatly enhances the formation of carboxylate ions compared to the FAMES. PMID- 24222624 TI - High-energy collision-induced dissociation of ceramide ions from permethylated glycosphingolipids. AB - Ceramide fragments from permethylated glycosphingolipids (GSLs) were studied by highenergy collision-induced dissociation (CID). In comparison with ceramlde fragments of underivatized GSLs, many more product ions including charge-remote fragment ions were observed. These ions provided detailed structural information on the ceramides. The relative intensity and the mass interval between the L and M ions were used to assign the position of the double bond. The position of the hydroxyl group was assigned with the Ln and K ions. Because the ceramide fragments and not the pseudomolecular ions were selected as the precursor ions, the size of GSLs had little effect on the quality of the product ion spectra. The sensitivity of this approach was in the range of picomoles. PMID- 24222625 TI - Characterization of the primary thermal degradation processes of peptides using the mass spectrometric technique K(+)IDS, K (+) ionization of desorbed species. AB - The mass spectrometric technique of K(+) ionization of desorbed species, K(+)IDS, is used here to characterize the primary thermal degradation chemistry of small peptides. In this technique, a small amount of a compound is rapidly heated in the condensed phase. Desorption of the intact molecule can occur. Also, thermal degradation products are formed which quickly desorb as well, rather than remain on the surface and undergo subsequent chemistry. The desorbed molecules form adducts with gas phase K(+) ions, and a mass spectrum is obtained. Deuterium labeling experiments, and the use of derivatizing reagents, allows for the thermal degradation chemistry of small peptides to be elucidated. Apparently, skeletal bond cleavages are accompanied by H-shifts, although the hydrogen atoms shift from "remote" sites, brought into close proximity with the fragmenting skeletal bond via secondary interactions. Experimental results are presented that allow for correlations between thermal degradation chemistry and the resulting K(+)IDS mass spectra to be made. PMID- 24222626 TI - Calibration Point for Electron Ionization MS / MS spectra measured with multiquadrupole mass spectrometers. AB - A protocol for establishing standard instrument conditions for measurement of product ion MS/MS spectra from parent ions produced by electron ionization is presented. Within this protocol, the ion at m/z 231 (C5F9 (+)) from perfluorokerosene or perfluorotributylamine is selected as the parent ion and subjected to collision-induced dissociation. The relative intensities of product ions at m/z 69, 131, and 181 are monitored as a function of collision energy while keeping the target gas pressure constant within the range of 10(-4)-10(-6) torr (measured), or a beam attenuation of approximately 30-70%. The collision energy at which the ion intensities for product ions at m/z 69 and 181 are equal is defined as the calibration point at that collision gas pressure; the intensity of the ion at m/z 131 is very close to this value as well. Electron ionization MS/MS spectra taken at the calibration point using two different multiquadrupole instruments show good reproducibility for several test compounds. The high degree of similarity may aid in the establishment of a MS/MS spectral library. PMID- 24222627 TI - Deflection of laser-produced ions in laser-induced thermal-desorption/fourier transform mass spectrometry for surface analysis. AB - A method for deflecting ions, such as K(+), produced outside a Fourier-transform mass spectrometer cell during laser-induced thermal desorption, is described. This technique has been shown to deflect laser-generated K and Ti ions from two Ti foil samples (biomedical implant model surfaces), yielding mass spectra of coadsorbed organic species. Further studies characterizing the laser desorption/deflection parameters have shown that ion deflection improves with higher deflection voltages and greater sample to Fourier-transform mass spectrometry cell separation. Higher laser power densities resulted in greater surface ion production; hence higher deflection voltages were necessary. A 6% increase in laser power necessitated a fourfold increase in deflection voltage for the Ti sample. PMID- 24222628 TI - Spontaneous and deflected drift-trajectories in orthogonal acceleration time-of flight mass spectrometry. AB - Orthogonal acceleration is a method for gating ions from an ion beam into a time of-flight (TOF) mass spectrometer. The technique involves a pulsed electric field to apply acceleration directed orthogonally to an ion beam. This approach is useful for coupling continuous ion sources to TOF mass analyzers. Most instruments of this type, which have been described in the literature, use steering electrodes after the orthogonal acceleration step. Those velocity components of ions originating from the ion beam velocity are minimized so that the deflected drift-trajectory is parallel to a transverse flight tube. In an alternative geometry the ion beam velocity is conserved and the drift-trajectory after the orthogonal acceleration step is spontaneous. The differences between the space-time focusing ability with spontaneous and deflected drift-trajectories are discussed and investigated. Trajectory calculations indicate that deflection fields placed after the orthogonal acceleration step distort the ion packet because, in this geometry, the flight-time to the detector is dependent on the position that the ions enter the steering optics. Increasing the duty-cycle efficiency by sampling longer sections of the continuous ion beam leads to a degradation of resolving power. Employing a spontaneous drift-trajectory after orthogonal acceleration provides the advantage that the arrival time spread for isobaric ions is, in principle, independent of the length of the ion beam sampled. The major implication of these findings is that simultaneously optimized sensitivity and resolving power may not be achievable with the deflected drift trajectory instruments. The calculations are in agreement with results from the published data of a number of groups who have built instruments based on the orthogonal acceleration principle. PMID- 24222629 TI - Chemical ionization mass spectrometery utilizing and isotopically labeled reagent gas. AB - The use of a mixture of 5% ammonia in methane, where the ammonia is 50% (15)N labeled, provides a very useful reagent gas for chemical ionization mass spectrometry. We find that this combination gives spectra very much like pure ammonia reagent gas except that all of the adduct ions are clearly labeled. PMID- 24222630 TI - Individual differences in negative affect and weekly variability in binge eating frequency. AB - OBJECTIVE: To examine the relationship of neuroticism and negative affect (NA) lability with weekly binge eating fluctuations between binge eating disorder (BED) and bulimia nervosa (BN). METHOD: Individuals with BED (n = 30) and BN (n = 54) from the community completed self-report measures at baseline and prospectively for 12 consecutive weeks. Weekly data were analyzed by using (mean) squared successive deviation to account for fluctuations in NA and binge eating from week to week. RESULTS: Generalized estimating equations revealed the presence of a two-way interaction between neuroticism and NA lability predicting binge eating fluctuations (Wald chi(2) = 8.25; df = 1; p = .004), indicating that higher NA lability was only related to larger fluctuations in the frequency of binge eating episodes when present in individuals who were also high on neuroticism. An interaction was also detected between eating disorder diagnosis and NA lability, but this was accounted for by differences in average NA between the diagnoses. DISCUSSION: This study highlights the relevance of two traits and their interaction in understanding individual differences in binge eating fluctuations. Additionally, findings indicate that diagnostic differences in average NA may impact binge eating fluctuations and NA lability. PMID- 24222631 TI - Risk factors and outcome of expanded-criteria donor kidney transplants in patients with low immunological risk. AB - QUESTIONS UNDER STUDY: The aim of this study was to evaluate risk factors and outcome of expanded-criteria donor (ECD) kidney transplants in patients with low immunological risk. METHODS: We evaluated graft survival and graft function in 265 recipients with low immunological risk defined as the absence of pretransplant donor-specific HLA antibodies. RESULTS: A total of 112 (42%) kidneys derived from ECD and 153 (58%) from standard-criteria donors (SCDs). Overall, in a multivariate Cox regression, ECD status was the only significant risk factor for graft failure (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.37; p = 0.01). In the SCD group there was an increased risk for graft failure with increasing recipient age (HR 1.06 per year, CI 1.01-1.10; p = 0.02) and in the ECD group a trend for risk reduction for recipients treated with tacrolimus (Tac) (HR 0.46, CI 0.20-1.06; p = 0.07). One, three and five-year graft survival of ECD kidneys was significantly better when recipients were treated with Tac (95%, 88% and 72%, respectively) than when they were treated without Tac (73%, 65% and 50%, respectively) (p = 0.008). At three years, ECD kidneys had a lower median estimated creatinine clearance (eCrCl) than SCD kidneys (37 vs 58 ml/min, p <0.001). Within the ECD group, recipients treated with Tac had a higher median eCrCl than those treated without Tac (41 ml/min vs 33 ml/min, p = 0.004). Graft function from one to three years was preserved in ECD recipients treated with Tac (median change 0.0 ml/min, p = 0.4) compared with those treated without Tac (median change -3.2 ml/min, p = 0.005). CONCLUSION: Tac based immunosuppression seems to improve graft survival and to preserve graft function in ECD kidneys with low immunological risk. PMID- 24222632 TI - Efferent and afferent connections of the olfactory bulb and prepiriform cortex in the pigeon (Columba livia). AB - Although olfaction in birds is known to be involved in a variety of behaviors, there is comparatively little detailed information on the olfactory brain. In the pigeon brain, the olfactory bulb (OB) is known to project to the prepiriform cortex (CPP), piriform cortex (CPi), and dorsolateral corticoid area (CDL), which together are called the olfactory pallium, but centrifugal pathways to the OB have not been fully explored. Fiber connections of CPi and CDL have been reported, but those of other olfactory pallial nuclei remain unknown. The present study examines the fiber connections of OB and CPP in pigeons to provide a more detailed picture of their connections using tract-tracing methods. When anterograde and retrograde tracers were injected in OB, projections to a more extensive olfactory pallium were revealed, including the anterior olfactory nucleus, CPP, densocellular part of the hyperpallium, tenia tecta, hippocampal continuation, CPi, and CDL. OB projected commissural fibers to the contralateral OB but did not receive afferents from the contralateral olfactory pallium. When tracers were injected in CPP, reciprocal ipsilateral connections with OB and nuclei of the olfactory pallium were observed, and CPP projected to the caudolateral nidopallium and the limbic system, including the hippocampal formation, septum, lateral hypothalamic nucleus, and lateral mammillary nucleus. These results show that the connections of OB have a wider distribution throughout the olfactory pallium than previously thought and that CPP provides a centrifugal projection to the OB and acts as a relay station to the limbic system. PMID- 24222633 TI - beta-chain extension: a new mode of carbon-carbon bond formation and chain extension by polyketide synthases. AB - The PKS tree gets a new branch: Hertweck and co-workers have uncovered the enzymology behind the novel beta-branching strategy used during Rhizoxin biosynthesis in Burholderia rhizoxinica. Both the KS and B domains are required for a delta-lactone to form by attack on the pre-existing polyketide chain; further chain extension must occur on the newly added beta-branching carbonyl. PMID- 24222634 TI - End of life care--the buck stops here with doctors. PMID- 24222636 TI - Quantitative control of intracellular signaling activity through chimeric receptors incorporating multiple identical tyrosine motifs. AB - Controlling activation levels and durations of native signaling molecules is important for efficiently controlling cellular fates. Previously we developed single-chain Fv (scFv)/cytokine receptor chimeras incorporating tyrosine motifs in the intracellular domain, which artificially control the activation of specific intracellular signaling proteins. In this study, to quantitatively control the activation levels of signaling molecules with an extended dynamic range, we constructed scFv/receptor chimeras incorporating multiple identical motifs at the different positions in the intracellular domain. We used retroviral transduction to express chimeric receptors with multiple STAT3 binding motifs connected with or without flexible linkers in a murine IL-3-dependent pro-B cell line, Ba/F3. Our results showed that the chimeric receptors can control the activation levels of STAT3 depending on ligand concentration and the number of motifs. The existence of linkers between the motifs also affected the signal intensity. Furthermore, the STAT3 activation levels significantly depended on the number of motifs rather than the distance from the JAK-binding region to the tyrosine motif. PMID- 24222637 TI - Iterative synthesis of nucleoside oligophosphates with phosphoramidites. AB - P-Amidites can be used in iterative couplings to selectively give mixed P(III) P(V) anhydrides. These intermediates can be oxidized followed by a rapid removal of the two terminal fluorenylmethyl groups. An iterative synthesis (coupling, oxidation, deprotection) of nucleoside oligophosphates can be carried out in solution and on a solid support. The coupling rates and yields are high, the procedures convenient (non-dry reagents and solvents, ambient conditions, unprotected nucleotides), and the purification is very simple. The method works with all canonical nucleosides and holds promise for significant simplification of the usually cumbersome process of P-anhydride bond construction. PMID- 24222638 TI - Evaluation of a novel photography-based home assessment protocol for identification of environmental risk factors for falls in elderly persons. AB - PRINCIPLES: To evaluate the validity and feasibility of a novel photography-based home assessment (PhoHA) protocol, as a possible substitute for on-site home assessment (OsHA). METHODS: A total of 20 patients aged >=65 years who were hospitalised in a rehabilitation centre for musculoskeletal disorders affecting mobility participated in this prospective validation study. For PhoHA, occupational therapists rated photographs and measurements of patients' homes provided by patients' confidants. For OsHA, occupational therapists conducted a conventional home visit. RESULTS: Information obtained by PhoHA was 79.1% complete (1,120 environmental factors identified by PhoHA vs 1416 by OsHA). Of the 1,120 factors, 749 had dichotomous (potential hazards) and 371 continuous scores (measurements with tape measure). Validity of PhoHA to potential hazards was good (sensitivity 78.9%, specificity 84.9%), except for two subdomains (pathways, slippery surfaces). Pearson's correlation coefficient for the validity of measurements was 0.87 (95% confidence interval [CI 0.80-0.92, p <0.001). Agreement between methods was 0.52 (95%CI 0.34-0.67, p <0.001, Cohen's kappa coefficient) for dichotomous and 0.86 (95%CI 0.79-0.91, p <0.001, intraclass correlation coefficient) for continuous scores. Costs of PhoHA were 53.0% lower than those of OsHA (p <0.001). CONCLUSIONS: PhoHA has good concurrent validity for environmental assessment if instructions for confidants are improved. PhoHA is potentially a cost-effective method for environmental assessment. PMID- 24222635 TI - Consensus paper: management of degenerative cerebellar disorders. AB - Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non invasive brain stimulation. PMID- 24222639 TI - Abdominal MRI at 3.0 T: LAVA-Flex compared with conventional fat suppression T1 weighted images. AB - PURPOSE: To study liver imaging with volume acceleration-flexible (LAVA-Flex) for abdominal magnetic resonance imaging (MRI) at 3.0 T and compare the image quality of abdominal organs between LAVA-Flex and fast spoiled gradient-recalled (FSPGR) T1-weighted imaging. MATERIALS AND METHODS: Our Institutional Review Board approval was obtained in this retrospective study. Sixty-nine subjects had both FSPGR and LAVA-Flex sequences. Two radiologists independently scored the acquisitions for image quality, fat suppression quality, and artifacts and the values obtained were compared with the Wilcoxon signed rank test. According to the signal intensity (SI) measurements, the uniformity of fat suppression, the contrast between muscle and fat and normal liver and liver lesions were compared by the paired t-test. The liver and spleen SI on the fat-only phase were analyzed in the fatty liver patients. RESULTS: Compared with FSPGR imaging, LAVA-Flex images had better and more homogenous fat suppression and lower susceptibility artifact (qualitative scores: 4.70 vs. 4.00, 4.86% vs. 7.14%, 4.60 and 4.10, respectively). The contrast between muscle and fat and between the liver and pathologic lesions was significantly improved on the LAVA-Flex sequence. The contrast value of the fatty liver and spleen was higher than that of the liver and spleen. CONCLUSION: The LAVA-Flex sequence offers superior and more homogenous fat suppression of the abdomen than does the FSPGR sequence. The fat only phase can be a simple and effective method of assessing fatty liver. PMID- 24222640 TI - On the nature of interactions between ionic liquids and small amino-acid-based biomolecules. AB - During the last decade, ionic liquids (ILs) have revealed promising properties and applications in many research fields, including biotechnology and biological sciences. The focus of this contribution is to give a critical review of the phenomena observed and current knowledge of the interactions occurring on a molecular basis. As opposed to the huge advances made in understanding the properties of proteins in ILs, complementary investigations dealing with interactions between ILs and peptides or oligopeptides are underrepresented and are mostly only of phenomenological nature. However, the field has received more attention in the last few years. This Review features a meta-analysis of the available data and findings and should, therefore, provide a basis for a scientifically profound understanding of the nature and mechanisms of interactions between ILs and structured or nonstructured peptides. Fundamental aspects of the interactions between different peptides/oligopeptides and ILs are complemented by sections on the experimental (spectroscopy, structural biology) and theoretical (computational chemistry) possibilities to explain the phenomena reported so far in the literature. In effect, this should lead to the development of novel applications and support the understanding of IL-solute interactions in general. PMID- 24222641 TI - Existence of independent C/EBPbeta 3'-UTR RNA in human tissues. PMID- 24222642 TI - Detection of mutations associated with resistance to rifampicin and isoniazid in Mycobacterium tuberculosis by polymerase chain reaction-ligase detection reaction. PMID- 24222643 TI - Plasmonic nanoprobes for real-time optical monitoring of nitric oxide inside living cells. AB - An optical sensor was developed for the quantitative determination of intracellular nitric oxide. The sensor consists of plasmonic nanoprobes that have a coating of mesoporous silica and an inner gold island film functionalized with a chemoreceptor for NO. PMID- 24222644 TI - Authors' reply to Brunet. PMID- 24222645 TI - Evaluation of donor factors contributing to plateletpheresis yields among apheresis platelet donors. AB - BACKGROUND: The University of California, Irvine Blood Donor Center operates a plateletpheresis donor program utilizing the Amicus Cell Separator. Plateletpheresis donors may donate one or more apheresis platelet (PLT) units per collection event. This study seeks to characterize UC Irvine's donor pool by identifying biometric and demographic attributes predictive of double product (DP) collections. STUDY DESIGN AND METHODS: Biometric, demographic and procedural data from 1,786 apheresis donors were collected and entered into Excel spreadsheets. Of the 1,786 successful plateletpheresis procedures performed from January 2009 to April 2012, 1,442 of the donations were performed using double needle (DN) kits. Only data from DN-kit collections were used for statistical analyses. The Classification And Regression Tree (CART) algorithm was used to help identify variables predictive of donating multiple PLT units in a single collection event. RESULTS: Donors weighing 75.7 kg or greater appear to be twice as likely to donate DPs as those weighing less than 75.7 kg. For donors weighing less than 75.7 kg, females appear to be twice as likely to donate DPs as males. Donors exhibiting platelet counts of 216.5 K/mcL or greater appear to be twice as likely to donate DPs as those with platelet counts fewer than 216.5 K/mcL. CONCLUSION: Weight, sex, and PLT count were identified as the most predictive donor attributes that separate UCI donors into DP donors and non-DP donors. Greater weights, greater PLT counts, and female sex confer to greater PLT yields per given amount of time. PMID- 24222646 TI - Breaking and building the wall: the biology of the blood-brain barrier in health and disease. AB - The blood-brain barrier (BBB) is a complex feature of brain endothelial cells that restricts the passage of blood-borne molecules into the brain parenchyma, while ensuring the delivery of essential nutrients and selected biomolecules. Brain vasculature is anatomically distinct from that of other organs and comprises in addition to endothelial cells, pericytes and astrocytes, which collectively form the neurovascular unit (NVU). This review focuses on the regulation of BBB properties by the NVU and the periphery. A brief overview of cellular components of the NVU, and BBB characteristics will be provided, with more emphasis placed on the molecular mechanisms involved in the development of brain vasculature and human genetic diseases primarily affected by dysfunction of components of the NVU. In addition, the regulation of brain vasculature by peripheral factors such as diet and systemic disease is discussed. PMID- 24222647 TI - Scaling the primate lateral geniculate nucleus: niche and neurodevelopment in the regulation of magnocellular and parvocellular cell number and nucleus volume. AB - New stereological assessments of lateral geniculate nucleus (LGN) neuron numbers and volumes in five New World primates (Cebus apella, Saguinus midas niger, Alouatta caraya, Aotus azarae, and Callicebus moloch) and compiled LGN volumes for an additional 26 mammals were analyzed for a better understanding of visual system evolution. Both the magnocellular (M)- and the parvocellular (P)-cell populations scale allometrically with brain volume in primates, P cells with a significantly higher slope such that, for every increase in M neuron number, P neuron numbers more than double (ln scale; y = 0.89x + 2.42R(2) = 0.664). In diurnal primates, the ratio of P to M cells was slightly but significantly higher than in nocturnal primates. For all mammals, including primates, LGN volume was unrelated to nocturnal or diurnal niche but showed marked differences in slope and intercept depending on taxonomic group. The allometric scaling of M and P cells can be related to the order of neurogenesis, with late-generated P cells increasing with positive allometry compared with the earlier-generated M cells. This developmental regularity links relative foveal representation to relative isocortex enlargement, which is also generated late. The small increase in the P/M cell ratio in diurnal primates may result from increased developmental neuron loss in the M-cell population as it competes for limited termination zones in primary visual cortex. PMID- 24222648 TI - Outside the lines and across the border. PMID- 24222649 TI - Supra-aortic arteries: three-dimensional time-resolved k-t BLAST contrast enhanced MRA using a nondedicated body coil at 3 tesla in acute ischemic stroke. AB - PURPOSE: To assess the image quality and diagnostic performance achieved by using supra-aortic 3D-TR-CE-k-t BLAST MRA and a nondedicated body coil as compared with conventional CE-MRA in patients with acute ischemic stroke. MATERIALS AND METHODS: In this prospective study, 36 consecutive patients with a suspected acute ischemic stroke underwent both k-t BLAST MRA and conventional CE-MRA. Image quality was assessed using visual and quantitative criteria and the techniques were compared. Both techniques were compared for degree of visual and quantitative measurement of carotid stenosis. RESULTS: Delineation of vessel lumen and overall diagnostic confidence were significantly better with CE-MRA, respectively 3.4 +/- 0.5 and 3.3 +/- 0.6 (mean score +/- SD), than with k-t BLAST MRA, respectively 2.8 +/- 0.4 and 2.9 +/- 0.5 (P < 0.02). SNR and CNR were significantly higher for k-t BLAST MRA, respectively 33.5 +/- 19.3 and 27.9 +/- 19.3, than for CE-MRA, respectively 25.7 +/- 10 and 20.4 +/- 8.4 (P < 0.03). Intertechnique agreement was good for carotid stenosis characterization (kappa = .763). For the 14 relevant stenosis, stenosis measurements were highly correlated between techniques (0.96; P < 0.0001). The Bland-Altman plot showed a low bias in assessment of the degree of stenosis (mean bias 2.1% +/- 7.7). CONCLUSION: k-t BLAST MRA using a nondedicated coil offering and dynamic information was a effective diagnostic tool for detection and characterization of carotid stenosis. PMID- 24222650 TI - FGF signaling emerged concomitantly with the origin of Eumetazoans. AB - Complex metazoan bodies require cell-to-cell communication for development, a process often mediated by signaling molecules binding to specific receptors. Relatively few signaling pathways have been recruited during evolution to build multicellular animals from unicellular zygotes. Of these few signaling pathways, one of particular importance is the receptor tyrosine kinase (RTK) pathway. In metazoans, fibroblast growth factors (FGFs) bind to receptors in the RTK family, but the origin of the FGF gene family has so far remained a mystery. Here we show that extant bona fide FGFs most likely originated from proteins bearing an FGF like domain that arose in a choanoflagellate/metazoan ancestor. We found orthologous genes closely related to FGF in choanoflagellates as well as in many metazoans such as sponges, acoels, protostomes, or nonvertebrate deuterostomes. We also show that these genes have a common evolutionary history with Retinitis Pigmentosa 1 (RP1). Even if some metazoan signaling pathways emerged long before multicellularity, we show that FGFs, like their receptors, originated in a eumetazoan ancestor. PMID- 24222651 TI - A redox-activated MRI contrast agent that switches between paramagnetic and diamagnetic states. PMID- 24222652 TI - Expression of somatostatin receptors, angiogenesis and proliferation markers in pituitary adenomas: an immunohistochemical study with diagnostic and therapeutic implications. AB - PRINCIPLES: Pituitary adenomas are common intracranial neoplasms that generate symptoms as a result of either mass effect or the increased production of pituitary hormones. Although mostly benign, these tumours can be associated with considerable morbidity. We investigated a panel of immunohistochemical preparations to identify potential therapeutic targets and surrogate markers of clinical outcome. METHODS: Tumour tissue from 25 patients was evaluated for immunohistochemical expression of somatostatin receptors 1-5, von Willebrand factor (vWF), interleukin-8 (IL-8), vascular endothelial growth factor receptor 2 (VEGFR-2), kinesin spindle protein (Eg5) and MIB-1 (Ki-67), and its relationship with clinical features was analysed. RESULTS: The proliferation marker MIB-1 (Ki 67) was the only marker predictive of adenoma recurrence. Of note, 67% of all relapses were associated with tumours showing luteinising hormone expression. All pituitary adenomas showed variable somatostatin receptor, IL-8, Eg5, vWF and VEGFR-2 expression; a relationship between these parameters and clinical outcome could not be demonstrated in this cohort. CONCLUSIONS: This study validates MIB-1 (Ki-67) as a reliable marker of tumour recurrence in pituitary adenomas. Considering the consistently increased expression of Eg5, IL-8, VEGFR-2, somatostatin receptors and vWF in these tumours, further investigation as potential therapeutic targets is warranted. PMID- 24222653 TI - In vivo relaxation behavior of liver compounds at 7 Tesla, measured by single voxel proton MR spectroscopy. AB - PURPOSE: To assess the proton T1 and T2 relaxation of in vivo hepatic water, choline and lipid resonances with possible J-coupling behavior of lipids in healthy volunteers at 7 Tesla (T). MATERIALS AND METHODS: Relaxation measurements were conducted on corn oil phantoms and on the hepatic tissue of 11 healthy volunteers at 7 T using a surface coil and a STEAM sequence. T1 's were determined by monoexponential fitting, and T2 's by both monoexponential and enhanced-exponential fitting (empirically designed to consider J-coupling of lipid resonances). RESULTS: In vivo T1 's at 7 T were estimated as follows: water (4.70 ppm), 1362 +/- 83 ms; methyl- (0.90 ppm), 1026 +/- 162 ms; methylene- (1.30 ppm), 514 +/- 25 ms; alpha-olefinic- (2.02 ppm), 488 +/- 220 ms; alpha-carboxyl- (2.24 ppm), 476 +/- 89 ms; diacyl- (2.77 ppm), 479 +/- 260 ms group of lipid chains; and choline compounds (3.22 ppm), 1084 +/- 52 ms. The T2 's calculated with enhanced fitting were as follows: water, 15 +/- 2 ms; methyl-, 34 +/- 10 ms; methylene-, 41 +/- 8 ms; alpha-olefinic-, 44 +/- 19 ms; alpha-carboxyl-, 39 +/- 15 ms; diacyl-, 44 +/- 5 ms group of lipid chains; and choline compounds, 32 +/- 9 ms. CONCLUSION: An accurate knowledge of in vivo relaxation and J-coupling behavior will significantly improve the quantification of an extended number of resolved liver metabolites at 7 T. PMID- 24222654 TI - Women who have had surgery for obesity have raised risk of preterm babies. PMID- 24222655 TI - Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats. AB - INTRODUCTION: Our previous study of angiotensin II receptor blocker (ARB) administration in rats induced unusual proliferative changes of smooth muscle cells in renal arteriolar walls. The present study examined if the incidence of the changes depended on the rats' age, and how long it would take to find changes. MATERIALS AND METHODS: Six-week-old (juvenile spontaneous hypertensive rats (SHRs)+ARB group, n=15) and 20-week-old (adult SHRs+ARB group, n=10) male SHRs were fed a standard diet (0.4% NaCl) containing valsartan (10 mg/kg/day; Novartis Co.). Fifteen age-matched SHRs were studied as controls. After 4, 8, and 12 weeks, the rat kidneys were examined under light and electron microscopes and through immunohistochemical studies. RESULTS: Extremely concentric proliferative changes in afferent arteriolar walls were frequently observed in the juvenile SHR+ARB group compared to the adult SHR+ARB group (48.7+/-6.8% vs 19.3+/-6.9%; p=0.0307) at the 12(th) week. Increased renin expression and arteriolar changes were found from the 4(th) week in the juvenile SHR+ARB group. CONCLUSION: This study indicates that ARB administration induces unusual proliferative changes and a marked renin-producing cell increase in afferent arterioles more frequently in juveniles than adult rats. It is suggested that the treatment of ARB in juveniles might have a higher risk of changes in renal afferent arterioles. PMID- 24222656 TI - New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension. AB - There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension. PMID- 24222657 TI - Trial will test whether shopping vouchers encourage breast feeding. PMID- 24222658 TI - Timely care for frail older people referred to hospital improves efficiency and reduces mortality without the need for extra resources. AB - BACKGROUND: hospitals are under pressure to reduce waiting times and costs. One strategy that may be effective focuses on optimising the flow of emergency patients. OBJECTIVE: we undertook a patient flow analysis of older emergency patients to identify and address delays in ensuring timely care, without additional resources. DESIGN: prospective systems redesign study over 2 years. SETTING: the Geriatric Medicine Directorate in an acute hospital (Sheffield Teaching Hospitals NHS Foundation Trust) with 1920 beds. SUBJECTS: older patients admitted as emergencies. METHODS: diagnostic patient flow analysis followed by a series of Plan Do Study Act cycles to test and implement changes by a multidisciplinary team using time series run charts. RESULTS: 60% of patients aged 75+ years arrived in the Emergency Department during office hours, but two thirds of the admissions to GM wards were outside office hours highlighting a major delay. Three changes were undertaken to address this, Discharge to Assess, Seven Day Working and the establishment of a Frailty Unit. Average bed occupancy fell by 20.4 beds (95% confidence interval (CI) -39.6 to -1.2, P = 0.037) for similar demand. The risk of hospital mortality also fell by 2.25% (before 11.4% (95% CI 10.4-12.4%), after 9.15% (95% CI 7.6-10.7%) which equates to a number needed to treat of 45 and a 19.7% reduction in relative risk of mortality. The risk of re-admission remained unchanged. CONCLUSION: redesigning the system of care for older emergency patients led to reductions in bed occupancy and mortality without affecting re-admission rates or requiring additional resources. PMID- 24222659 TI - Drug cessation in complex older adults: time for action. AB - BACKGROUND: general opinion is growing that drug cessation in complex older patients is warranted in certain situations. From a clinical viewpoint, drug cessation seems most warranted in four situations, i.e., falls, delirium, cognitive impairment and end-of-life situations. To date, little information about the effects of drug cessation in these four situations is available. OBJECTIVES: to identify the effects and effectiveness of drug cessation on falls, delirium and cognitive impairment. For end-of-life situations, we reviewed cessation of inappropriate drug use. METHODS: electronic databases were searched using MeSH terms and relevant keywords. Studies published in English were included if they evaluated the effects of drug cessation in older persons, aged >=65 years, with falls, delirium or cognitive impairment; or cessation of inappropriate drug use in end-of-life situations. RESULTS: we selected seven articles for falls, none for delirium, two for cognition and two for end-of-life situations. Withdrawal of psychotropics reduced fall rate; a prescribing modification programme for primary care physicians reduced fall risk. Withdrawal of psychotropics and a systematic reduction of polypharmacy resulted in an improvement of cognition. Very little rigorous research has been conducted on reducing inappropriate medications in patients approaching end of life. CONCLUSION: little research has focussed on drug cessation. Available studies showed a beneficial impact of cessation of psychotropic drugs on falls and cognitive status. More research in this field is needed. The issue of systematic drug withdrawal in end-of-life cases is controversial, but is increasingly relevant in the face of rising numbers of older people of this clinical status. PMID- 24222660 TI - Sonographic findings in the diagnosis of HIV-associated tuberculosis: image quality and inter-observer agreement in FASH vs. remote-FASH ultrasound. PMID- 24222662 TI - Lappaol F, a novel anticancer agent isolated from plant arctium Lappa L. AB - In an effort to search for new cancer-fighting therapeutics, we identified a novel anticancer constituent, Lappaol F, from plant Arctium Lappa L. Lappaol F suppressed cancer cell growth in a time- and dose-dependent manner in human cancer cell lines of various tissue types. We found that Lappaol F induced G(1) and G(2) cell-cycle arrest, which was associated with strong induction of p21 and p27 and reduction of cyclin B1 and cyclin-dependent kinase 1 (CDK1). Depletion of p21 via genetic knockout or short hairpin RNA (shRNA) approaches significantly abrogated Lappaol F-mediated G(2) arrest and CDK1 and cyclin B1 suppression. These results suggest that p21 seems to play a crucial role in Lappaol F-mediated regulation of CDK1 and cyclin B1 and G(2) arrest. Lappaol F-mediated p21 induction was found to occur at the mRNA level and involved p21 promoter activation. Lappaol F was also found to induce cell death in several cancer cell lines and to activate caspases. In contrast with its strong growth inhibitory effects on tumor cells, Lappaol F had minimal cytotoxic effects on nontumorigenic epithelial cells tested. Importantly, our data also demonstrate that Lappaol F exhibited strong growth inhibition of xenograft tumors in nude mice. Lappaol F was well tolerated in treated animals without significant toxicity. Taken together, our results, for the first time, demonstrate that Lappaol F exhibits antitumor activity in vitro and in vivo and has strong potential to be developed as an anticancer therapeutic. PMID- 24222661 TI - Low levels of circulating estrogen sensitize PTEN-null endometrial tumors to PARP inhibition in vivo. AB - Earlier in vitro work demonstrated that PARP inhibition induces cell death in PTEN-null endometrial cancer cell lines, but the in vivo therapeutic efficacy of these agents against endometrial cancer remains unknown. Here, we test the efficacy of AZD2281 (olaparib), an oral PARP inhibitor, in the therapy of PTEN null endometrial tumors in a preclinical endometrial cancer mouse model. Primary endometrial tumors were generated by epithelial loss of PTEN using an in vivo model. This model recapitulates epithelial-specific loss of PTEN seen in human tumors, and histologically resembles endometrioid carcinomas, the predominant subtype of human endometrial cancers. Olaparib was administered orally to tumor bearing mice in two hormonal extremes: high or low estrogen. Olaparib treatment achieved a significant reduction in tumor size in a low estrogenic milieu. In striking contrast, no response to olaparib was seen in tumors exposed to high levels of estrogen. Two key observations were made when estrogen levels were dropped: (i) the serum concentration of olaparib was significantly increased, resulting in sustained PARP inhibition at the tumor bed; and (ii) the homologous recombination pathway was compromised, as evidenced by decreased Rad51 protein expression and function. These two mechanisms may account for the sensitization of PTEN-null tumors to olaparib with estrogen deprivation. Results of this preclinical trial suggest that orally administered PARP inhibitors in a low estrogenic hormonal milieu can effectively target PTEN-null endometrial tumors. Extension of this work to clinical trials could personalize the therapy of women afflicted with advanced endometrial cancer using well-tolerated orally administered therapeutic agents. PMID- 24222663 TI - Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer. AB - Penetration of the bladder permeability barrier (BPB) is a major challenge when treating bladder diseases via intravesical delivery. To increase transurothelial migration and tissue and tumor cell uptake, poly(lactic-co-glycolic acid; PLGA) nanoparticles (NP) were modified by addition of a low molecular weight (2.5 or 20 kDa) positively charged mucoadhesive polysaccharide, chitosan, to the NP surface. In designing these NPs, we balanced the adhesive properties of chitosan with the release and bioactivity of the siRNA. Chitosan-functionalized NPs demonstrated increased binding to and uptake in intravesically instilled mouse bladders and human ureter at 10 times the level of unmodified NPs. Furthermore, we extended the bioactivity of survivin siRNA in vitro for up to 9 days and demonstrated a decrease in proliferation when using chitosan-modified NPs relative to unmodified NPs. In addition, treatment of xenograft tumors with chitosan-modified NPs that encapsulate survivin siRNA (NP-siSUR-CH2.5) resulted in a 65% reduction in tumor volume and a 75% decrease in survivin expression relative to tumors treated with blank chitosan NPs (NP-Bk-CH2.5). Our low molecular weight chitosan delivery system has the capacity to transport large amounts of siRNA across the urothelium and/or to the tumor site, thus increasing therapeutic response. PMID- 24222665 TI - NHS medical director proposes two tier emergency service. PMID- 24222664 TI - Response to MLN8237 in pancreatic cancer is not dependent on RalA phosphorylation. AB - The high prevalence of KRAS mutations and importance of the RalGEF-Ral pathway downstream of activated K-ras in pancreatic ductal adenocarcinoma (PDAC) emphasize the importance of identifying novel methods by which to therapeutically target these pathways. It was recently demonstrated that phosphorylation of RalA S194 by Aurora A kinase (AAK) is critical for PDAC tumorigenesis. We sought to evaluate the AAK-selective inhibitor MLN8237 as a potential indirect anti-RalA targeted therapy for PDAC. We used a site-specific phospho-S194 RalA antibody and determined that RalA S194 phosphorylation levels were elevated in a subset of PDAC cell lines and human tumors relative to unmatched normal controls. Effects of MLN8237 on anchorage-independent growth in PDAC cell lines and growth of patient-derived xenografts (PDX) were variable, with a subset of cell lines and PDX showing sensitivity. Surprisingly, RalA S194 phosphorylation levels in PDAC cell lines or PDX tumors did not correlate with MLN8237 responsiveness. However, we identified Ki67 as a possible early predictive biomarker for response to MLN8237 in PDAC. These results indicate that MLN8237 treatment may be effective for a subset of patients with PDAC independent of RalA S194 phosphorylation. Ki67 may be an effective pharmacodynamic biomarker to identify response early in the course of treatment. PMID- 24222667 TI - Response to cold pressor test predicts long-term changes in pulse wave velocity in men. AB - BACKGROUND: Aortic stiffness is associated with increased cardiovascular mortality. However, the determinants of aortic stiffness progression are not fully established. This study evaluated the predictive value of blood pressure (BP) response to cold pressor test (CPT) in the progression of carotid-femoral pulse wave velocity (PWV) in men and women. METHODS: A total of 408 individuals (165 men, 243 women) from Vitoria, Brazil, underwent BP evaluation, clinical and laboratorial investigations, and CPT and PWV assessment. Five years later, the studied individuals were re-evaluated, except for the CPT. RESULTS: In men, 5 year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with BP response to CPT (P < 0.05) and 5-year BP change (P < 0.05). In women, 5 year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with age (P < 0.01), glycemia (P < 0.05) and 5-year BP change (P < 0.05) but not with BP response to CPT. Further linear regression analysis showed that 5-year PWV change was associated with baseline PWV, systolic BP response to CPT, and 5 year systolic BP change in men and with baseline PWV, age, glycemia, and 5-year systolic BP change in women. CONCLUSIONS: BP response to CPT was a predictor of PWV progression in men after 5 years of follow-up. These findings provide further insights into the pathophysiologic mechanisms of arterial stiffness, suggesting that elevated sympathetic reactivity may be a predisposing factor for future increases in aortic stiffness, at least in men. PMID- 24222666 TI - Ankle brachial index values, leg symptoms, and functional performance among community-dwelling older men and women in the lifestyle interventions and independence for elders study. AB - BACKGROUND: The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community-dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower-extremity functional performance in the LIFE Study population. METHODS AND RESULTS: Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400-m walk, and 4-m walking velocity. Participants were classified as follows: definite PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), low normal ABI (ABI 1.00 to 1.09), and no PAD (ABI 1.10 to 1.40). Of 1566 participants, 220 (14%) had definite PAD, 250 (16%) had borderline PAD, 509 (33%) had low normal ABI, and 587 (37%) had no PAD. Among those with definite PAD, 65% were asymptomatic. Adjusting for age, sex, race, body mass index, smoking, and comorbidities, lower ABI was associated with longer mean 400-m walk time: (definite PAD=533 seconds; borderline PAD=514 seconds; low normal ABI=503 seconds; and no PAD=498 seconds [P<0.001]). Among asymptomatic participants with and without PAD, lower ABI values were also associated with longer 400-m walk time (P<0.001) and slower walking velocity (P=0.042). CONCLUSION: Among older community-dwelling men and women, 14% had PAD and 49% had borderline or low normal ABI values. Lower ABI values were associated with greater functional impairment, suggesting that lower extremity atherosclerosis may be a common preventable cause of functional limitations in older people. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/ Unique identifier: NCT01072500. PMID- 24222668 TI - PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. AB - The proton-coupled amino acid transporter 1 (PAT1) is a transporter of amino acids in small intestinal enterocytes. PAT1 is, however, also capable of regulating cell growth and sensing the availability of amino acids in other cell types. The aim of the present study was to investigate the localization and function of PAT1 in smooth muscle cells (SMCs). The PAT1 protein was found in smooth muscles from rat intestine and in the embryonic rat aorta cell line A7r5. Immunolocalization and cellular fractionation studies revealed that the majority of the PAT1 protein located within the cell nucleus of A7r5 cells. These results were confirmed in primary SMCs derived from rat aorta and colon. A 3' untranslated region of the PAT1 transcript directed the nuclear localization. Neither cellular starvation nor cell division altered the nuclear localization. In agreement, uptake studies of l-proline, a PAT1 substrate, in A7r5 cells suggested an alternative role for PAT1 in SMCs than in transport. To shed light on the function of PAT1 in A7r5 cells, experiments with downregulation of the PAT1 level by use of a siRNA approach were conducted. The growth rates of the cells were evaluated, and knockdown of PAT1 led to induced cellular growth, suggesting a role for PAT1 in regulating cellular proliferation of SMCs. PMID- 24222669 TI - G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. AB - Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood. Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120). Addition of GW-9508 (a GPR120 chemical agonist) and alpha-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ~50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pretreatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice. These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells. PMID- 24222670 TI - Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice. AB - The mineralocorticoid receptor (MR) exerts proadipogenic and antithermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high-fat diet (HFD) for 16 wk. Tg mice had a lower body weight gain than WT animals and exhibited a relative resistance to HFD-induced obesity. This was associated with a decrease in fat mass, an increased population of smaller adipocytes, and an improved glucose tolerance compared with WT animals. Quantitative RT-PCR studies revealed decreased expression of PPARgamma2, a master adipogenic gene, and of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 1, consistent with an impaired local glucocorticoid signaling in adipose tissues (AT). This paradoxical resistance to HFD-induced obesity was not related to an adipogenesis defect since differentiation capacity of Tg preadipocytes isolated from stroma-vascular fractions was unaltered, suggesting that other nonadipocyte factors might compromise AT development. Although AT macrophage infiltration was not different between genotypes, Tg mice exhibited a distinct macrophage polarization, as revealed by FACS analysis and CD11c/CD206 expression studies. We further demonstrated that Tg macrophage-conditioned medium partially impaired preadipocyte differentiation. Therefore, we propose that modification of M1/M2 polarization of hMR-overexpressing macrophages could account in part for the metabolic phenotype of Tg mice. Collectively, our results provide evidence that MR exerts a pivotal immunometabolic role by controlling adipocyte differentiation processes directly but also indirectly through macrophage polarization regulation. Our findings should be taken into account for the pharmacological treatment of metabolic disorders. PMID- 24222672 TI - Breadlines, brains, and behaviour. PMID- 24222671 TI - ICD-10 codes used to identify adverse drug events in administrative data: a systematic review. AB - BACKGROUND: Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. METHODS: We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. RESULTS: Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156-289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0-59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. CONCLUSIONS: Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area. PMID- 24222673 TI - Putting GlaxoSmithKline to the test over paroxetine. PMID- 24222674 TI - A shot in the arm for medical education. PMID- 24222675 TI - Academics who spoke out on swine flu risks were more likely to have industry links, study finds. PMID- 24222676 TI - Shortage of health workers is set to double, says WHO. PMID- 24222677 TI - Obamacare's rocky road. PMID- 24222678 TI - Brain-machine interface. PMID- 24222680 TI - Most doctors have negative experiences of reporting incidents. PMID- 24222681 TI - Influence of light conditions on the allometry and growth of the understory palm Geonoma undata subsp. edulis (Arecaceae) of neotropical cloud forests. AB - PREMISE OF THE STUDY: Knowledge on the growth responses of understory palms to changing light conditions within neotropical cloud forests is limited. The low light regime of these environments, in addition to persistent cloudiness, low ambient temperatures, and slow nutrient cycles, imposes significant constraints on biomass accumulation. Here, we evaluate how changes in the understory light conditions influenced the allometry and growth of G. undata subsp. edulis in two cloud forests in Costa Rica. METHODS: We examined the structural relationships between stem diameter, stem height, and crown area in reproductive and nonreproductive individuals. We related the variation in stem growth and crown area with allometry, leaf production and longevity, and light conditions that we measured using hemispherical photographs over 1 year. KEY RESULTS: The allometric and growth pattern of G. undata subsp. edulis was characterized by its investment in crown area, which was strongly and positively related to increments in palm height and reproduction. Growth, measured as the increase in crown area and stem height, was not explained by the variation in the light regime spanning 1 year. However, reproductive individuals were generally taller, more slender, and had larger leaf areas than nonreproductive individuals. CONCLUSIONS: Our results demonstrated that stem growth responses were mostly controlled by initial crown size rather than by temporal differences in the understory light regimes of cloud forests. These results suggest that cloud forest understory palms have a limited capacity to respond to light changes and rely mostly on an opportunistic strategy for biomass accumulation and reproduction. PMID- 24222682 TI - Fire structures pine serotiny at different scales. AB - PREMISE OF THE STUDY: Serotiny (delayed seed release with the consequent accumulation of a canopy seedbank) confers fitness benefits in environments with crown-fire regimes. Thus, we predicted that serotiny level should be higher in populations recurrently subjected to crown-fires than in populations where crown fires are rare. In addition, under a high frequency of fires, space and resources are recurrently available, permitting recruitment around each mother to follow the seed rain shadow. Thus, we also predicted spatial aggregation of serotiny within populations. METHODS: We compared serotiny, considering both the proportion and the age of serotinous cones, in populations living in contrasting fire regimes for two iconic Mediterranean pine species (Pinus halepensis, P. pinaster). We framed our results by quantitatively comparing the strength of the fire-serotiny relationship with previous studies worldwide. KEY RESULTS: For the two species, populations living under high crown-fire recurrence regimes had a higher serotiny level than those populations where the recurrence of crown-fires was low. For P. halepensis (the species with higher serotiny), populations in high fire recurrence regimes had higher fine-scale spatial aggregation of serotiny than those inhabiting low fire recurrence systems. The strength of the observed fire-serotiny relationship in P. halepensis is among the highest in published literature. CONCLUSIONS: Fire regime shapes serotiny level among populations, and in populations with high serotiny, recurrent fires maintain a significant spatial structure for this trait. Consequently, fire has long-term evolutionary implications at different scales, emphasizing its prominent role in shaping the ecology of pines. PMID- 24222683 TI - Dementia statistic is misleading. PMID- 24222685 TI - Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins. AB - Matrix mechanics controls cell fate by modulating the bonds between integrins and extracellular matrix (ECM) proteins. However, it remains unclear how fibronectin (FN), type 1 collagen, and their receptor integrin subtypes distinctly control force transmission to regulate focal adhesion kinase (FAK) activity, a crucial molecular signal governing cell adhesion/migration. Here we showed, using a genetically encoded FAK biosensor based on fluorescence resonance energy transfer, that FN-mediated FAK activation is dependent on the mechanical tension, which may expose its otherwise hidden FN synergy site to integrin alpha5. In sharp contrast, the ligation between the constitutively exposed binding motif of type 1 collagen and its receptor integrin alpha2 was surprisingly tension independent to induce sufficient FAK activation. Although integrin alpha subunit determines mechanosensitivity, the ligation between alpha subunit and the ECM proteins converges at the integrin beta1 activation to induce FAK activation. We further discovered that the interaction of the N-terminal protein 4.1/ezrin/redixin/moesin basic patch with phosphatidylinositol 4,5-biphosphate is crucial during cell adhesion to maintain the FAK activation from the inhibitory effect of nearby protein 4.1/ezrin/redixin/moesin acidic sites. Therefore, different ECM proteins either can transmit or can shield from mechanical forces to regulate cellular functions, with the accessibility of ECM binding motifs by their specific integrin alpha subunits determining the biophysical mechanisms of FAK activation during mechanotransduction. PMID- 24222686 TI - BMP-9 balances endothelial cell fate. PMID- 24222688 TI - Transcription-factor binding and sliding on DNA studied using micro- and macroscopic models. AB - Transcription factors search for specific operator sequences by alternating rounds of 3D diffusion with rounds of 1D diffusion (sliding) along the DNA. The details of such sliding have largely been beyond direct experimental observation. For this purpose we devised an analytical formulation of umbrella sampling along a helical coordinate, and from extensive and fully atomistic simulations we quantified the free-energy landscapes that underlie the sliding dynamics and dissociation kinetics for the LacI dimer. The resulting potential of mean force distributions show a fine structure with an amplitude of 1 k(B)T for sliding and 12 k(B)T for dissociation. Based on the free-energy calculations the repressor slides in close contact with DNA for 8 bp on average before making a microscopic dissociation. By combining the microscopic molecular-dynamics calculations with Brownian simulation including rotational diffusion from the microscopically dissociated state we estimate a macroscopic residence time of 48 ms at the same DNA segment and an in vitro sliding distance of 240 bp. The sliding distance is in agreement with previous in vitro sliding-length estimates. The in vitro prediction for the macroscopic residence time also compares favorably to what we measure by single-molecule imaging of nonspecifically bound fluorescently labeled LacI in living cells. The investigation adds to our understanding of transcription-factor search kinetics and connects the macro-/mesoscopic rate constants to the microscopic dynamics. PMID- 24222691 TI - Haemodialysis: hospital or home? AB - Healthcare costs associated with the provision of dialysis therapy are escalating globally as the number of patients developing end-stage renal disease increases. In this setting, there has been heightened interest in the application and potential benefit of home haemodialysis therapies compared with the conventional approach of thrice weekly, incentre treatments. Increasingly, national healthcare systems are financially incentivising the expansion of home haemodialysis programmes with observational studies demonstrating better patient survival, superior control of circulating volume and blood pressure, greater patient satisfaction and lower running costs compared with incentre dialysis. Nonetheless, increasing the prevalence of home haemodialysis is challenged by the technological complexity of conventional dialysis systems, the need for significant adaptations to the home as well as suboptimal clinician and patient education about the feasibility and availability of this modality. In addition, enthusiasm about frequent as well as nocturnal (extended-hours) haemodialysis has been tempered by results from the recent Frequent Haemodialysis Network randomised controlled trials comparing these schedules with a conventional incentre regime. An increasing emphasis on empowering patient choice and promoting self-management of chronic illness is a powerful driver for the expansion of home haemodialysis programmes in the UK and internationally. PMID- 24222690 TI - Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes. AB - To enable discovery of serum antibodies indicative of disease and simultaneously develop reagents suitable for diagnosis, in vitro directed evolution was applied to identify consensus peptides recognized by patients' serum antibodies. Bacterial cell-displayed peptide libraries were quantitatively screened for binders to serum antibodies from patients with celiac disease (CD), using cell sorting instrumentation to identify two distinct consensus epitope families specific to CD patients (PEQ and (E)/DxFV(Y)/FQ). Evolution of the (E)/DxFV(Y)/FQ consensus epitope identified a celiac-specific epitope, distinct from the two CD hallmark antigens tissue transglutaminase-2 and deamidated gliadin, exhibiting 71% sensitivity and 99% specificity (n = 231). Expansion of the first-generation PEQ consensus epitope via in vitro evolution yielded octapeptides QPEQAFPE and PFPEQxFP that identified omega- and gamma-gliadins, and their deamidated forms, as immunodominant B-cell epitopes in wheat and related cereal proteins. The evolved octapeptides, but not first-generation peptides, discriminated one-way blinded CD and non-CD sera (n = 78) with exceptional accuracy, yielding 100% sensitivity and 98% specificity. Because this method, termed antibody diagnostics via evolution of peptides, does not require prior knowledge of pathobiology, it may be broadly useful for de novo discovery of antibody biomarkers and reagents for their detection. PMID- 24222692 TI - A mystery solved. PMID- 24222693 TI - Moisture and mydriasis. PMID- 24222694 TI - PCP prophylaxis with use of corticosteroids by neurologists. AB - Pneumocystis jirovecii pneumonia (PCP) is increasingly reported in patients without HIV. Corticosteroids are a major risk factor, with up to 90% of patients receiving corticosteroid treatment prior to the development of PCP. In view of this, many specialties now prescribe PCP prophylaxis to patients receiving prolonged or high-dose glucocorticoid regimens. Neurologists frequently prescribe corticosteroids but may not be as aware of the risk for PCP. Here, we review the evidence for routine PCP prophylaxis among regular glucocorticoid users and ask what guidance there is on the subject for neurologists. PMID- 24222697 TI - HIV testing in dementia: test some, perhaps more, but not all. PMID- 24222696 TI - Test them all; an easily diagnosed and readily treatable cause of dementia with life-threatening consequences if missed. PMID- 24222701 TI - Saddle pulmonary thromboembolism. PMID- 24222702 TI - Prinzmetal angina. PMID- 24222703 TI - Physical activity impairment in depressed COPD subjects. AB - BACKGROUND: Limited exercise tolerance is a cardinal clinical feature in COPD. Depression and COPD share some clinical features, such as reduced physical activity and impaired nutritional status. The aim of the present study was to evaluate maximum and daily physical activities and the nutritional status of COPD patients affected or not by depression. METHODS: In 70 COPD out-patients, daily and maximum physical activities were assessed by multisensor accelerometer armband, 6-min walk test, and cardiopulmonary exercise test. Mental status, metabolic/muscular status, and systemic inflammation were evaluated using the Hospital Anxiety and Depression Scale, by bioelectrical impedance analysis, and with regard to fibrinogen/C-reactive protein, respectively. RESULTS: Depressed subjects (27% of the sample) showed a similar level of respiratory functional impairment but a higher level of shortness of breath and a worse quality of life compared to non-depressed subjects (P < .05). Specifically, they displayed a physical activity impairment consisting of a reduced number of steps per day, a lower peak of oxygen consumption, an early anaerobic threshold, and a reduced distance in the 6-min walk test (P < .05) but the same nutritional status compared to non-depressed subjects. In the multivariate analysis, a reduced breathing reserve, obesity, and a higher level of shortness of breath, but not depression, were found to be independent factors associated with a reduced daily number of steps. CONCLUSIONS: Our study found that depressed COPD patients have a reduced daily and maximum exercise capacity compared to non-depressed patients. This further suggests the potential utility of screening for depression in COPD. PMID- 24222704 TI - Acute effects of volume-oriented incentive spirometry on chest wall volumes in patients after a stroke. AB - BACKGROUND: The aim of the present study was to assess how volume-oriented incentive spirometry applied to patients after a stroke modifies the total and compartmental chest wall volume variations, including both the right and left hemithoraces, compared with controls. METHODS: Twenty poststroke patients and 20 age-matched healthy subjects were studied by optoelectronic plethysmography during spontaneous quiet breathing (QB), during incentive spirometry, and during the recovery period after incentive spirometry. RESULTS: Incentive spirometry was associated with an increased chest wall volume measured at the pulmonary rib cage, abdominal rib cage and abdominal compartment (P = .001) and under 3 conditions (P < .001). Compared with healthy control subjects, the tidal volume (VT) of the subjects with stroke was 24.7, 18.0, and 14.7% lower during QB, incentive spirometry, and postincentive spirometry, respectively. Under all 3 conditions, the contribution of the abdominal compartment to VT was greater in the stroke subjects (54.1, 43.2, and 48.9%) than in the control subjects (43.7, 40.8, and 46.1%, P = .039). In the vast majority of subjects (13/20 and 18/20 during QB and incentive spirometry, respectively), abdominal expansion precedes rib cage expansion during inspiration. Greater asymmetry between the right and left hemithoracic expansions occurred in stroke subjects compared with control subjects, but it decreased during QB (62.5%, P = .002), during incentive spirometry (19.7%), and postincentive spirometry (67.6%, P = .14). CONCLUSIONS: Incentive spirometry promotes increased expansion in all compartments of the chest wall and reduces asymmetric expansion between the right and left parts of the pulmonary rib cage; therefore, it should be considered as a tool for rehabilitation. PMID- 24222705 TI - Estimating breathing movements of the chest and abdominal wall using a simple, newly developed breathing movement-measuring device. AB - BACKGROUND: The 3-dimensional (3D) distances of specific points on the chest and abdominal wall are useful for assessing the characteristics of breathing movement. This study aimed to determine whether the 3D distances on the chest and abdominal wall during deep breathing (DB) could be estimated using a newly developed breathing movement-measuring device (BMMD). METHODS: Breathing movement distances on the chest (bilateral third and eighth ribs) and abdomen (upper abdomen) of 10 healthy young males were measured using a pen-sized mechanical BMMD and a 3D motion analysis system during DB. DB was controlled and based on the distances targeted by the BMMD (ie, 1, 2, and 3 cm), which was placed on the observation points and fixed on a tripod. Simultaneously, the 3D distances of reflective markers on the observation points were measured. The obtained data were statistically analyzed using a paired t test, repeated measures analysis of variance with multiple comparisons tests, and linear regression with mixed effects. RESULTS: All the BMMD distances were less than the 3D distances. The differences between the 3D and BMMD distances on the chest and abdomen, except for the left lower chest (eighth rib), were significantly greater at a target distance of 3 cm than that of 1 cm. The coefficients of determination ranged from 0.98 to 0.99. CONCLUSIONS: Linear regression equations provided adequate estimates of the 3D distances of markers on the chest and abdominal wall during DB. The results suggest that this BMMD is useful for quantitatively assessing DB movement of the chest and abdominal wall in healthy young males. PMID- 24222706 TI - Disease management programs for patients with COPD in Germany: a longitudinal evaluation of routinely collected patient records. AB - INTRODUCTION: The primary aim of the disease management program (DMP) for patients with COPD is to improve health outcomes and thereby to reduce overall costs. Six years after its introduction in Germany, no consensus has yet been reached as to whether the DMP has been effective in reaching these goals. The objective of the study was an evaluation of the DMP for COPD in Bavaria using routinely collected subject medical records. METHODS: A longitudinal population based study, comparing the total DMP population of up to 86,560 patients with a stable cohort of 17,549 subjects over a period of 5 years. The effect of subject dropout in the cohort is further estimated by means of inverse probability weighting. RESULTS: The proportion of subjects in the total population who were prescribed and received treatment with oral corticosteroids declined at a constant rate of 1.0% per year (P < .001). The proportion of subjects who were given a prescription for theophylline decreased at a constant rate of 2.0% per year (P < .001). By 2012, 15.6% of the total population and 26% of the cohort had undergone self-management education. While the proportion of smokers in the total population remained constant because of the effect of newly enrolled subjects, the proportion of smokers decreased significantly even after dropout adjustment, from 29% to 21%. The occurrence of exacerbations decreased steadily at a rate of 0.9% (total population) or 0.7% (cohort) per year. While the occurrence of emergency hospital admissions decreased in the total population, an increase was observed within the cohort. CONCLUSIONS: Summarizing all results leads to the suggestion that the German DMP for COPD has been effective in enhancing the quality of care in regard to an improved adherence to guidelines, pharmacotherapy, exacerbations, and self-management education. However, the DMP was not able to prevent an increase in emergency hospital admissions for the stable population in the cohort. PMID- 24222707 TI - Ex vivo assessment and validation of water exchange performance of 23 heat and moisture exchangers for laryngectomized patients. AB - BACKGROUND: Breathing through a tracheostoma results in insufficient warming and humidification of the inspired air. This loss of air conditioning, especially humidification, can be partially restored with the application of a heat and moisture exchanger (HME) over the tracheostoma. For medical professionals, it is not easy to judge differences in water exchange performance of various HMEs owing to the lack of universal outcome measures. This study has three aims: assessment of the water exchange performance of commercially available HMEs for laryngectomized patients, validation of these results with absolute humidity outcomes, and assessment of the role of hygroscopic salt present in some of the tested HMEs. METHODS: Measurements of weight and absolute humidity at end inspiration and end expiration at different breathing volumes of a healthy volunteer were performed using a microbalance and humidity sensor. Twenty-three HMEs from 6 different manufacturers were tested. Associations were determined between core weight, weight change, breathing volume, and absolute humidity, using both linear and nonlinear mixed effects models. RESULTS: Water exchange of the 23 HMEs at a breathing volume of 0.5 L varies between 0.5 and 3.6 mg. Both water exchange and wet core weight correlate strongly with the end-inspiratory absolute humidity values (r2 =0.89/0.87). Hygroscopic salt increases core weight. CONCLUSIONS: The 23 tested HMEs for laryngectomized patients show wide variation in water exchange performance. Water exchange correlates well with the end inspiratory absolute humidity outcome, which validates the ex vivo weight change method. Wet core weight is a predictor of HME performance. Hygroscopic salt increases the weight of the core material. The results of this study can help medical professionals to obtain a more founded opinion about the performance of available HMEs for pulmonary rehabilitation in laryngectomized patients, and allow them to make an informed decision about which HME type to use. PMID- 24222708 TI - Nonpharmacologic airway clearance techniques in hospitalized patients: a systematic review. AB - Nonpharmacologic airway clearance techniques are used to reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of nonpharmacologic interventions that health professionals can employ to achieve mucus clearance in hospitalized or postoperative patients without cystic fibrosis, over the age of 12 months. We searched MEDLINE and other databases from 1990 to 2012 to identify relevant literature. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers also independently extracted data regarding subject and intervention characteristics and outcomes, and assigned overall quality ratings. The 32 studies meeting the review criteria included 24 randomized controlled trials, 7 crossover randomized controlled trials, and one prospective cohort study. Studies were typically small and together included a total of 2,453 subjects (mean 76/study). Studies generally examined chest physical therapy/physiotherapy modalities in postoperative or critically ill subjects or those with COPD. Interventions, comparators, and populations varied considerably across studies, hampering our ability to draw firm conclusions. Interventions, including conventional chest physical therapy/physiotherapy, intrapulmonary percussive ventilation, and positive expiratory pressure, typically provided small benefits in pulmonary function, gas exchange, oxygenation, and need for/duration of ventilation, among other outcomes, but differences between groups were generally small and not significant. Harms of the techniques were not consistently reported, though airway clearance techniques were generally considered safe in studies that did comment on adverse effects. Further research with clearly characterized populations and interventions is needed to understand the potential benefits and harms of these techniques. PMID- 24222709 TI - AARC clinical practice guideline: effectiveness of nonpharmacologic airway clearance therapies in hospitalized patients. AB - Airway clearance therapy (ACT) is used in a variety of settings for a variety of ailments. These guidelines were developed from a systematic review with the purpose of determining whether the use of nonpharmacologic ACT improves oxygenation, reduces length of time on the ventilator, reduces stay in the ICU, resolves atelectasis/consolidation, and/or improves respiratory mechanics, versus usual care in 3 populations. For hospitalized, adult and pediatric patients without cystic fibrosis, 1) chest physiotherapy (CPT) is not recommended for the routine treatment of uncomplicated pneumonia; 2) ACT is not recommended for routine use in patients with COPD; 3) ACT may be considered in patients with COPD with symptomatic secretion retention, guided by patient preference, toleration, and effectiveness of therapy; 4) ACT is not recommended if the patient is able to mobilize secretions with cough, but instruction in effective cough technique may be useful. For adult and pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough, 1) cough assist techniques should be used in patients with neuromuscular disease, particularly when peak cough flow is < 270 L/min; CPT, positive expiratory pressure, intrapulmonary percussive ventilation, and high-frequency chest wall compression cannot be recommended, due to insufficient evidence. For postoperative adult and pediatric patients, 1) incentive spirometry is not recommended for routine, prophylactic use in postoperative patients, 2) early mobility and ambulation is recommended to reduce postoperative complications and promote airway clearance, 3) ACT is not recommended for routine postoperative care. The lack of available high-level evidence related to ACT should prompt the design and completion of properly designed studies to determine the appropriate role for these therapies. PMID- 24222710 TI - Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma. AB - Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma. MCNPX calculations of out-of-field doses were done for ~20 different organs considering realistic treatment plans and using computational phantoms representative of an adult male individual. Simulations showed higher secondary neutron doses for intracranial treatments, ~14 mGy to the salivary glands, when compared with ocular treatments, ~0.6 mGy to the non-treated eye. This secondary dose increase is mainly due to the higher proton beam energy (178 vs. 75 MeV) as well as to the impact of the different beam parameters (modulation, collimation, field size etc.). Moreover, when compared with published data, the assessed secondary neutron doses showed similar trends, but sometimes with sensitive differences. This confirms secondary neutrons to be directly dependent on beam energy, modulation technique, treatment configuration and methodology. PMID- 24222711 TI - An indirect in vivo dosimetry system for ocular proton therapy. AB - Secondary radiation, particularly neutron radiation, is a cause of concern in proton therapy. However, one can take advantage of its presence by using it to retrieve useful information on the primary proton beam. At the Centre Antoine Lacassagne the secondary radiation in the treatment room has been studied in function of the beam modulation. A strong correlation was found between the secondary ambient dose equivalent per proton dose H*(10)/D and proton dose rate D/MU. A large volume ionisation chamber fixed on the wall at 2.5 m from the nozzle was used with an in-house computer interface to retrieve the value of D/MU derived from the measurement of photon H*(10) integrated over treatment time, using the correlation curve. This system enables the verification of D and D/MU to be made independently of the monitoring of the primary beam and represents a first step towards an alternative in vivo dosimetry in proton therapy. PMID- 24222712 TI - Existential neuroscience: self-esteem moderates neuronal responses to mortality related stimuli. AB - According to terror management theory, self-esteem serves as a buffer against existential anxiety. This proposition is well supported empirically, but its neuronal underpinnings are poorly understood. Therefore, in the present neuroimaging study, our aim was to test how self-esteem affects our neural circuitry activation when death-related material is processed. Consistent with previous findings, the bilateral insula responded less to death-related stimuli relative to similarly unpleasant, but death-unrelated sentences, an effect that might reflect a decrease in the sense of oneself in the face of existential threat. In anterior parts of the insula, this 'deactivation' effect was more pronounced for high self-esteem individuals, suggesting that the insula might be of core importance to understanding the anxiety-buffering effect of self-esteem. In addition, low self-esteem participants responded with enhanced activation to death-related over unpleasant stimuli in bilateral ventrolateral prefrontal and medial orbitofrontal cortex, suggesting that regulating death-related thoughts might be more effortful to these individuals. Together, this suggests that the anxiety-buffering effect of self-esteem might be implemented in the brain in the form of both insula-dependent awareness mechanisms and prefrontal cortex dependent regulation mechanisms. PMID- 24222713 TI - Regulation of epithelial morphogenesis by the G protein-coupled receptor mist and its ligand fog. AB - Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells and used RNA interference-based screening to identify Mist, a Drosophila G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID- 24222715 TI - Race and the Response of State Legislatures to Unauthorized Immigrants. AB - Increasingly, state legislatures are enacting laws to regulate immigrant populations. What accounts for these responses to foreign-born residents? To explain legislative activity at the state level, the authors examine a variety of factors, including the size and growth of foreign-born and Hispanic local populations, economic well-being, crime rates, and conservative or liberal political ideology in state government and among the citizenry. The authors find that economic indicators, crime rates, and demographic changes have little explanatory value for legislation aimed at restrictions on immigrant populations. Rather, conservative citizen ideology appears to drive immigrant-related restrictionist state legislation. Meanwhile, proimmigrant laws are associated with larger Hispanic concentrations, growing foreign-born populations, and more liberal citizen and governmental orientations. These findings suggest that ideological framing is the most consistently important factor determining legislative responses to newcomers. These findings are in line with the relatively scarce empirical literature on legislative tendencies associated with vulnerable populations. PMID- 24222714 TI - The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo. AB - The activation of the small guanosine triphosphatase Ras by the guanine nucleotide exchange factor (GEF) Sos1 (Son of Sevenless 1) is a central feature of many receptor-stimulated signaling pathways. In developing T cells (thymocytes), Sos1-dependent activation of extracellular signal-regulated kinase (ERK) is required to stimulate cellular proliferation and differentiation. We showed that in addition to its GEF activity, Sos1 acted as a scaffold to nucleate oligomerization of the T cell adaptor protein LAT (linker for activation of T cells) in vivo. The scaffold function of Sos1 depended on its ability to bind to the adaptor protein Grb2. Furthermore, the GEF activity of Sos1 and the Sos1 dependent oligomerization of LAT were separable functions in vivo. Whereas the GEF activity of Sos1 was required for optimal ERK phosphorylation in response to T cell receptor (TCR) stimulation, the Sos1-dependent oligomerization of LAT was required for maximal TCR-dependent phosphorylation and activation of phospholipase C-gamma1 and Ca(2+) signaling. Finally, both of these Sos1 functions were required for early thymocyte proliferation. Whereas transgenic restoration of either the GEF activity or the LAT oligomerization functions of Sos1 alone failed to rescue thymocyte development in Sos1-deficient mice, simultaneous reconstitution of these two signals in the same cell restored normal T cell development. This ability of Sos1 to act both as a RasGEF and as a scaffold to nucleate Grb2-dependent adaptor oligomerization may also occur in other Grb2-dependent pathways, such as those activated by growth factor receptors. PMID- 24222716 TI - Development and validation of an ELISA at acidic pH for the quantitative determination of IL-13 in human plasma and serum. AB - A novel sandwich ELISA for the quantitative and sensitive determination of IL-13 in human serum and plasma was established. The assay employs an incubation step at acidic pH, which was shown to decrease nonspecific binding and interference from IL-13 binding proteins. The assay was validated and was shown to be accurate and precise over the entire quantification range (0.59 to 68.4 pg/mL in human EDTA plasma). The validated assay was successfully applied to samples from healthy volunteers and patients with atopic seasonal rhinitis. The assay is suitable for use in clinical trials to monitor efficacy or pharmacodynamic effects of drug candidates. PMID- 24222717 TI - Activin A and follistatin as biomarkers for ectopic pregnancy and missed abortion. AB - Activin A as a predictor of pregnancy failure has been the focus of heated debate, but the value of a combined activin A and follistatin (FS) measurement in serum to predict pregnancy failure has not been reported yet. We assessed whether a single serum measurement of the two physiological antagonists at 6-8 weeks gestation could differentiate ectopic pregnancies (EP) or missed abortions (MA) from healthy intrauterine pregnancies (IUP). activin A concentrations were significantly lower in women with EP (n = 30, median value of 264 pg/mL) and women with MA (n = 30, median value of 350 pg/mL) compared to IUP (n = 33, median value of 788 pg/mL); P < 0.001. At a threshold value of 505 pg/mL, activin A had 87.9% sensitivity and 100% specificity and negative predictive value of 0.974 for discriminating an ectopic pregnancy from viable pregnancies. FS was able to discriminate IUP from EP (ROC curve P < 0.001) as was their ratio (ROC curve P = 0.008), but was unable to discriminate a MA from an EP. In EP, activin A did not correlate with beta HCG levels. The present findings support the thesis that activin A or FS could be considered promising biomarkers for the discrimination between an IUP and a failed pregnancy (MA or EP). PMID- 24222718 TI - When bilinguals choose a single word to speak: Electrophysiological evidence for inhibition of the native language. AB - Behavioral and event-related potential (ERP) measures are reported for a study in which relatively proficient Chinese-English bilinguals named identical pictures in each of their two languages. Production occurred only in Chinese (the first language, L1) or only in English (the second language, L2) in a given block with the order counterbalanced across participants. The repetition of pictures across blocks was expected to produce facilitation in the form of faster responses and more positive ERPs. However, we hypothesized that if both languages are activated when naming one language alone, there might be evidence of inhibition of the stronger L1 to enable naming in the weaker L2. Behavioral data revealed the dominance of Chinese relative to English, with overall faster and more accurate naming performance in L1 than L2. However, reaction times for naming in L1 after naming in L2 showed no repetition advantage and the ERP data showed greater negativity when pictures were named in L1 following L2. This greater negativity for repeated items suggests the presence of inhibition rather than facilitation alone. Critically, the asymmetric negativity associated with the L1 when it followed the L2 endured beyond the immediate switch of language, implying long lasting inhibition of the L1. In contrast, when L2 naming followed L1, both behavioral and ERP evidence produced a facilitatory pattern, consistent with repetition priming. Taken together, the results support a model of bilingual lexical production in which candidates in both languages compete for selection, with inhibition of the more dominant L1 when planning speech in the less dominant L2. We discuss the implications for modeling the scope and time course of inhibitory processes. PMID- 24222719 TI - Effect of therapeutic inhibition of TNF on circulating endothelial progenitor cells in patients with rheumatoid arthritis. AB - Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P = 0.001). After 3 months EPCs increased significantly (P = 0.0006) while ADMA levels significantly decreased (P = 0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r = -0.56, P = 0.04). EPCs inversely correlated with ADMA (r = -0.41, P = 0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function. PMID- 24222720 TI - Relationship between serum transforming growth factor beta 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents. AB - The aim of this study was to evaluate the relationship between serum transforming growth factor beta 1 (TGF- beta 1) concentrations and the duration of type 1 diabetes mellitus (T1DM) in children and adolescents. One hundred and sixteen patients with T1DM and 19 healthy controls were examined. Serum TGF- beta 1 concentrations were measured using the cytometric bead array (CBA). A positive association between the time of diabetes duration and higher serum TGF- beta 1 concentrations was observed. Similarly, the prevalence of microvascular complications, such as retinopathy and nephropathy, increased with the duration of diabetes. Logistic regression analysis showed that serum TGF- beta 1 concentrations and the duration of the disease are independent risk factors of microangiopathy development. Higher serum TGF- beta 1 concentrations were associated with a significant risk of microangiopathy development after 10 years of T1DM duration. In the successive years of the disease, the effect was even stronger. The results of our study indicate that serum TGF- beta 1 concentrations are one of the factors that may have an impact on the progression of vascular complications in children and adolescents with T1DM. PMID- 24222721 TI - Activity Logs as a Measure of Daily Activity Among Patients with Chronic Fatigue Syndrome. AB - BACKGROUND: Self-report data collected through interviews has been one of the primary ways of assessing symptoms of patients with chronic fatigue syndrome (CFS). An alternative way to collect data involves activity logs, which involves patients writing down the pattern, intensity, and qualitative nature of activity over several days. AIMS: We examined the associations between activity, evaluation of activity and symptoms. METHODS: Activity log data over a two day period of time were used in the present study using a sample of patients with diagnosed CFS. RESULTS: Findings indicated that the percent of time spent feeling fatigued was positively associated with a higher percent of time in pain and doing activities that were fatiguing. However, time spent in meaningful activities was associated with less fatigue. CONCLUSIONS: These findings and others suggest that activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of behavior and activity among patients with CFS. PMID- 24222722 TI - Neighborhood Dynamics of Urban Violence: Understanding the Immigration Connection. AB - Social disorganization is the dominant framework linking neighborhood patterns of immigration to local rates of crime and violence despite inconsistent findings and evidence to the contrary. Using tract-level census data from 1970 to 1990 and Chicago homicide data from 1980 to 1995, this study explores whether and how the changing face of immigration is (un)related to homicide patterns within the contemporary urban environment. The results show that stable and consistent growth in foreign born is not associated with neighborhood trends in violence, whereas growth in recent arrivals occurs almost exclusively within the safest neighborhoods of the city. This research highlights the need to distinguish recent waves of immigrants/migrants from their historic counterparts. PMID- 24222723 TI - The Doryctinae (Braconidae) of Costa Rica: genera and species of the tribe Heterospilini. AB - A comprehensive taxonomic study is presented for the four genera and 286 species of the doryctine tribe Heterospilini occurring in Costa Rica. The tribe is represented almost entirely by the 280 species of the genus Heterospilus Haliday. Keys for identification of the genera and species are provided and the genera and species are described and illustrated. An interactive key to the species of Heterospilus also was prepared using Lucid Builder. The following new genus and species are described from Costa Rica: Paraheterospilus gen. n., P. ceciliaensis sp. n., P. eumekus sp. n., P. wilbotgardus sp. n., Heterospilus achi sp. n., H. achterbergi sp. n., H. aesculapius sp. n., H. agujas sp. n., H. agujasensis sp. n., H. alajuelus sp. n., H. albocoxalis sp. n., H. alejandroi sp. n., H. amuzgo sp. n., H. angelicae sp. n., H. angustus sp. n., H. aphrodite sp. n., H. apollo sp. n., H. arawak sp. n., H. areolatus sp. n., H. artemis sp. n., H. athena sp. n., H. attraholucus sp. n., H. aubreyae sp. n., H. austini sp. n., H. azofeifai sp. n., H. bacchus sp. n., H. barbalhoae sp. n., H. bennetti sp. n., H. bicolor sp. n., H. boharti sp. n., H. borucas sp. n., H. braeti sp. n., H. brethesi sp. n., H. breviarius sp. n., H. brevicornus sp. n., H. bribri sp. n., H. brullei sp. n., H. bruesi sp. n., H. cabecares sp. n., H. cacaoensis sp. n., H. cachiensis sp. n., H. cameroni sp. n., H. cangrejaensis sp. n., H. careonotaulus sp. n., H. caritus sp. n., H. carolinae sp. n., H. cartagoensis sp. n., H. catiensis sp. n., H. catorce sp. n., H. cero sp. n., H. chaoi sp. n., H. chilamatensis sp. n., H. chocho sp. n., H. chorotegus sp. n., H. chorti sp. n., H. cinco sp. n., H. cocopa sp. n., H. colliletus sp. n., H. colonensis sp. n., H. complanatus sp. n., H. conservatus sp. n., H. cora sp. n., H. corcovado sp. n., H. corrugatus sp. n., H. costaricensis sp. n., H. cressoni sp. n., H. cuatro sp. n., H. curtisi sp. n., H. cushmani sp. n., H. dani sp. n., H. demeter sp. n., H. dianae sp. n., H. diecinueve sp. n., H. dieciocho sp. n., H. dieciseis sp. n., H. diecisiete sp. n., H. diez sp. n., H. doce sp. n., H. dos sp. n., H. dulcus sp. n., H. eberhardi sp. n., H. ektorincon sp. n., H. emilius sp. n., H. empalmensis sp. n., H. enderleini sp. n., H. escazuensis sp. n., H. fahringeri sp. n., H. fischeri sp. n., H. flavidus sp. n., H. flavisoma sp. n., H. flavostigmus sp. n., H. foersteri sp. n., H. fonsecai sp. n., H. fournieri sp. n., H. gahani sp. n., H. garifuna sp. n., H. gauldi sp. n., H. golfodulcensis sp. n., H. gouleti sp. n., H. granulatus sp. n., H. grisselli sp. n., H. guanacastensis sp. n., H. guapilensis sp. n., H. hachaensis sp. n., H. halidayi sp. n., H. hansoni sp. n., H. hansonorum sp. n., H. haplocarinus sp. n., H. hedqvisti sp. n., H. hera sp. n., H. heredius sp. n., H. hespenheidei sp. n., H. holleyae sp. n., H. huddlestoni sp. n., H. huetares sp. n., H. hypermekus sp. n., H. itza sp. n., H. ixcatec sp. n., H. ixil sp. n., H. jabillosensis sp. n., H. jakaltek sp. n., H. janzeni sp. n., H. jennieae sp. n., H. jonmarshi sp. n., H. jupiter sp. n., H. kellieae sp. n., H. kiefferi sp. n., H. kikapu sp. n., H. kulai sp. n., H. kuna sp. n., H. lapierrei sp. n., H. lasalturus sp. n., H. laselvus sp. n., H. leenderti sp. n., H. leioenopus sp. n., H. leiponotaulus sp. n., H. lenca sp. n., H. levis sp. n., H. leviscutum sp. n., H. levitergum sp. n., H. limonensis sp. n., H. longinoi sp. n., H. longisulcus sp. n., H. longius sp. n., H. luteogaster sp. n., H. luteoscutum sp. n., H. luteus sp. n., H. macrocarinus sp. n., H. macrocaudatus sp. n., H. magnus sp. n., H. malaisei sp. n., H. mam sp. n., H. maritzaensis sp. n., H. mars sp. n., H. masneri sp. n., H. masoni sp. n., H. mellosus sp. n., H. menkei sp. n., H. mercury sp. n., H. milleri sp. n., H. miskito sp. n., H. mixtec sp. n., H. monteverde sp. n., H. mopanmaya sp. n., H. muertensis sp. n., H. muesebecki sp. n., H. nahua sp. n., H. neesi sp. n., H. nemestrinus sp. n., H. nephilim sp. n., H. nephus sp. n., H. nigracapitus sp. n., H. nigragonatus sp. n., H. nigricoxus sp. n., H. nixoni sp. n., H. noyesi sp. n., H. nueve sp. n., H. nunesi sp. n., H. once sp. n., H. orbitus sp. n., H. orosi sp. n., H. paloverde sp. n., H. pappi sp. n., H. parkeri sp. n., H. parvus sp. n., H. pech sp. n., H. penosa sp. n., H. petiolatus sp. n., H. petralbus sp. n., H. phaeocoxus sp. n., H. phaeoskelus sp. n., H. pharkidodus sp. n., H. phytorius sp. n., H. pitillaensis sp. n., H. poqomchi sp. n., H. poqomom sp. n., H. puertoviejoensis sp. n., H. puntarensis sp. n., H. qanjobal sp. n., H. quickei sp. n., H. quitirrisi sp. n., H. racostica sp. n., H. rama sp. n., H. ramirezi sp. n., H. ratzeburgi sp. n., H. reagani sp. n., H. reinhardi sp. n., H. retheospilus sp. n., H. rhabdotus sp. n., H. ricacosta sp. n., H. rinconensis sp. n., H. robbieae sp. n., H. rohweri sp. n., H. rojasi sp. n., H. romani sp. n., H. rugosus sp. n., H. sabrinae sp. n., H. saminae sp. n., H. sanjosensis sp. n., H. santarosensis sp. n., H. sanvitoensis sp. n., H. saturn sp. n., H. seis sp. n., H. sergeyi sp. n., H. sharkeyi sp. n., H. shawi sp. n., H. shenefelti sp. n., H. shonan sp. n., H. siete sp. n., H. similis sp. n., H. sinuatus sp. n., H. smithi sp. n., H. spiloheterus sp. n., H. staryi sp. n., H. stelfoxi sp. n., H. strazanaci sp. n., H. sumo sp. n., H. szepligeti sp. n., H. terrabas sp. n., H. thereospilus sp. n., H. tobiasi sp. n., H. tolupan sp. n., H. townesi sp. n., H. trece sp. n., H. tres sp. n., H. tricolor sp. n., H. trienta sp. n., H. tuberculatus sp. n., H. turrialbaensis sp. n., H. tzutujil sp. n., H. ugaldei sp. n., H. uno sp. n., H. variabilis sp. n., H. veinte sp. n., H. veintidos sp. n., H. veintitres sp. n., H. veintiuno sp. n., H. vierecki sp. n., H. villegasi sp. n., H. vittatus sp. n., H. vulcanus sp. n., H. wahli sp. n., H. warreni sp. n., H. washingtoni sp. n., H. wesmaeli sp. n., H. whartoni sp. n., H. whitfieldi sp. n., H. wildi sp. n., H. wilkinsoni sp. n., H. wrightae sp. n., H. xanthus sp. n., H. xerxes sp. n., H. xinca sp. n., H. yaqui sp. n., H. ypsilon sp. n., H. zapotec sp. n., H. zeus sp. n., H. zitaniae sp. n., H. zoque sp. n., H. zunigai sp. n., H. zurquiensis sp. n. One new combination is proposed, Pioscelus costaricensis (Marsh) comb. n. PMID- 24222724 TI - The vascularized fibular graft in the pediatric upper extremity: a durable, biological solution to large oncologic defects. AB - Skeletal reconstruction after large tumor resection is challenging. The free vascularized fibular graft (FVFG) offers the potential for rapid autograft incorporation as well as growing physeal transfer in pediatric patients. We retrospectively reviewed eleven pediatric patients treated with FVFG reconstructions of the upper extremity after tumor resection. Eight male and three female patients were identified, including four who underwent epiphyseal transfer. All eleven patients retained a functional salvaged limb. Nonunion and graft fracture were the most common complications relating to graft site (27%). Peroneal nerve palsy occurred in 4/11 patients, all of whom received epiphyseal transfer. Patients receiving epiphyseal transplant had a mean annual growth of 1.7 cm/year. Mean graft hypertrophy index increased by more than 10% in all cases. Although a high complication rate may be anticipated, the free vascularized fibula may be used to reconstruct large skeletal defects in the pediatric upper extremity after oncologic resection. Transferring the vascularized physis is a viable option when longitudinal growth is desired. PMID- 24222725 TI - SUFREN LOS NINOS : EXPLORING THE IMPACT OF UNAUTHORIZED IMMIGRATION STATUS ON CHILDREN'S WELL-BEING. AB - The present study examines the effect of unauthorized immigration status on child well-being at a time of elevated immigration rates, economic decline, and unprecedented local lawmaking related to immigration. Immigrant families today are likely to differ from those of the past in that they are more likely to be from Latin America or the Caribbean and include unprecedented numbers of unauthorized immigrants. In addition, they are settling in destinations that have not historically had immigrant populations. The present study draws on interviews with 40 families from an emerging immigrant destination in north central Indiana to help illuminate the ways in which unauthorized immigration status influences child well-being. Results illustrate that unauthorized status extends beyond the individual to families and that mixed-status family situations create unique challenges for these families. More specifically, these results show the ways in which unauthorized immigrant status may impact family stress and uncertainty, health outcomes, and educational attainment and may result in increased social isolation for children in immigrant families. PMID- 24222726 TI - A mathematical model of tumor volume changes during radiotherapy. AB - PURPOSE: To develop a clinically viable mathematical model that quantitatively predicts tumor volume change during radiotherapy in order to provide treatment response assessment for prognosis, treatment plan optimization, and adaptation. METHOD AND MATERIALS: The correction factors containing hypoxia, DNA single strand breaks, potentially lethal damage, and other factors were used to develop an improved cell survival model based on the popular linear-quadratic model of cell survival in radiotherapy. The four-level cell population model proposed by Chvetsov et al. was further simplified by removing the initial hypoxic fraction and reoxygenation parameter, which are hard to obtain in routine clinics, such that an easy-to-use model can be developed for clinical applications. The new model was validated with data of nine lung and cervical cancer patients. RESULTS: Out of the nine cases, the new model can predict tumor volume change in six cases with a correlation index R (2) greater than 0.9 and the rest of three with R (2) greater than 0.85. CONCLUSION: Based on a four-level cell population model, a more practical and simplified cell survival curve was proposed to model the tumor volume changes during radiotherapy. Validation study with patient data demonstrated feasibility and clinical usefulness of the new model in predicting tumor volume change in radiotherapy. PMID- 24222727 TI - Children with congenital hypothyroidism have similar neuroradiological abnormal findings as healthy ones. AB - OBJECTIVE: To assess the neuroradiological findings of children with congenital hypothyroidism (CHT) compared to healthy controls (HC). PATIENTS AND METHODS: Thirty children with CHT, mean age 12.5 +/- 1.6 years, 14 (44.8%) males, were compared with 38 HC mean age 11.7 +/- 1.7 years, 16 (45.7%) males. Clinical data were collected from medical charts and questionnaires seeking information on family history, birth and perinatal period events, medications, and overall health history. Neurocognitive function was assessed for global intelligence, visual and verbal memory, and executive functioning using standardized tests. Neuroimaging was performed using 1.5 T magnetic resonance imaging and assessed by two pediatric radiologists. RESULTS: Children with CHT had a similar proportion of incidental findings as did the children in the HC group, at 43.3% and 39.5%, respectively, P = 0.69. Abnormalities of the sellar region were reported in 13.3% of CHT group and 7.9% of HC group, P = 0.46. Other incidental findings included cerebellar ectopia, choroidal fissure and pineal cysts, and multiple increased signal intensity foci. Neuroradiological findings were not associated with clinical and neurocognitive abnormalities. CONCLUSION: Neuroimaging of children with CHT demonstrated a similar incidence of structural abnormalities as in the healthy population. There is no association between those findings and neurocognitive function. PMID- 24222728 TI - Thermal infrared anomalies of several strong earthquakes. AB - In the history of earthquake thermal infrared research, it is undeniable that before and after strong earthquakes there are significant thermal infrared anomalies which have been interpreted as preseismic precursor in earthquake prediction and forecasting. In this paper, we studied the characteristics of thermal radiation observed before and after the 8 great earthquakes with magnitude up to Ms7.0 by using the satellite infrared remote sensing information. We used new types of data and method to extract the useful anomaly information. Based on the analyses of 8 earthquakes, we got the results as follows. (1) There are significant thermal radiation anomalies before and after earthquakes for all cases. The overall performance of anomalies includes two main stages: expanding first and narrowing later. We easily extracted and identified such seismic anomalies by method of "time-frequency relative power spectrum." (2) There exist evident and different characteristic periods and magnitudes of thermal abnormal radiation for each case. (3) Thermal radiation anomalies are closely related to the geological structure. (4) Thermal radiation has obvious characteristics in abnormal duration, range, and morphology. In summary, we should be sure that earthquake thermal infrared anomalies as useful earthquake precursor can be used in earthquake prediction and forecasting. PMID- 24222729 TI - Voluntary exercise prevents lead-induced elevation of oxidative stress and inflammation markers in male rat blood. AB - Regular mild exercise enhances antioxidant and anti-inflammatory systems of the body. The present study investigates voluntary exercise effects on lead toxicity as a known oxidative stressor. Male Sprague-Dawley rats were randomly divided into 2 groups. Sedentary control: the animals were housed 7 weeks in the regular cages. Exercise group: the animals were housed 7 weeks in the running wheel equipped cages, that is, the animal model of voluntary exercise. During the 7th week, all animals were administered lead acetate. Blood samples were collected at the end of the 6th week and 7th week (before and after lead administrations). Glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and tumor necrosis factor (TNF-alpha) were measured in the samples. Our results showed that lead administration reduced blood SOD, GPx and CAT and increased TNF-alpha; in the controls, but in the exercise group, changes were not statistically significant. MDA in both groups increased after lead injections but it was significantly lower in exercise group compared to the sedentary animals. We concluded that voluntary exercise may be considered as a preventive tool against lead-induced oxidative stress and inflammation. PMID- 24222730 TI - Muscle sensor model using small scale optical device for pattern recognitions. AB - A new sensor system for measuring contraction and relaxation of muscles by using a PANDA ring resonator is proposed. The small scale optical device is designed and configured to perform the coupling effects between the changes in optical device phase shift and human facial muscle movement, which can be used to form the relationship between optical phase shift and muscle movement. By using the Optiwave and MATLAB programs, the results obtained have shown that the measurement of the contraction and relaxation of muscles can be obtained after the muscle movements, in which the unique pattern of individual muscle movement from facial expression can be established. The obtained simulation results, that is, interference signal patterns, can be used to form the various pattern recognitions, which are useful for the human machine interface and the human computer interface application and discussed in detail. PMID- 24222731 TI - Sonication: a valuable technique for diagnosis and treatment of periprosthetic joint infections. AB - BACKGROUND: Periprosthetic joint infection (PJI) is the most severe complication, following joint arthroplasty. Identification of the causal microbial factor is of paramount importance for the successful treatment. PURPOSE: The aim of this study is to compare the sonication fluid cultures derived from joint prosthetic components with the respective periprosthetic tissue cultures. METHODS: Explanted prosthesis components for suspected infection were placed into a tank containing sterile Ringer's solution and sonicated for 1 minute at 40 kHz. Sonication fluid cultures were examined for 10 days, and the number and identity of any colony morphology was recorded. In addition, periprosthetic tissue specimens (>5) were collected and cultured according to standard practice. The duration of antimicrobial interruption interval before culture sampling was recorded. RESULTS: Thirty-four patients composed the study group. Sonication fluid cultures were positive in 24 patients (70.5%). Sixteen of thirty four periprosthetic tissue cultures (47.1%) were considered positive, all revealing the same microbial species with the respective sonication fluid cultures: 3 tissue samples showed polymicrobial infection. All tissue cultures were also found positive by the sonication fluid culture. CONCLUSIONS: Sonication fluid cultures represent a cheap, easy, accurate, and sensitive diagnostic modality demonstrating increased sensitivity compared to periprosthetic tissue cultures (70.5 versus 47.1%). PMID- 24222732 TI - Expression and significance of microRNA-183 in hepatocellular carcinoma. AB - OBJECTIVE: In our previous study, we found that some miRNAs were deregulated in hepatocellular carcinoma (HCC), including miR-183. However, the expression of miR 183 in the progression of benign liver diseases to HCC and its correlation with clinicopathologic factors remain undefined. METHODS: MiR-183 expression was measured in normal controls (NC) (n = 21), chronic viral hepatitis B or C (CH) tissues (n = 10), liver cirrhosis (LC) tissues (n = 18), HCC tissues (n = 92), and adjacent nontumor tissues (NT) (n = 92) by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The expression levels of miR-183 were significantly higher in HCC than in NT, LC, CH, and NL (P = 0.001, P < 0.001, P = 0.011, P < 0.001, resp.). The upregulated miR-183 in HCC was correlated with TNM stage (P = 0.042) and cirrhosis (P = 0.025). The Kaplan Meier survival analysis showed that miR-183 expression was not associated with the survival of HCC patients. However, miR-183 yielded an area under the curve (AUC) of 0.808 with 59.8% sensitivity and 91.8% specificity in discriminating HCC from benign liver diseases (CH and LC) or NC. CONCLUSIONS: The upregulated miR 183 may associate with onset and progression of HCC, but not with the patient survival. A further research is needed to determine the potential of miR-183 as biomarker for HCC. PMID- 24222733 TI - A CPW-fed circular wide-slot UWB antenna with wide tunable and flexible reconfigurable dual notch bands. AB - A coplanar waveguide (CPW)-fed circular slot antenna with wide tunable dual band notched function and frequency reconfigurable characteristic is designed, and its performance is verified experimentally for ultra-wideband (UWB) communication applications. The dual band-notched function is achieved by using a T-shaped stepped impedance resonator (T-SIR) inserted inside the circular ring radiation patch and by etching a parallel stub loaded resonator (PSLR) in the CPW transmission line, while the wide tunable bands can be implemented by adjusting the dimensions of the T-SIR and the PSLR. The notch band reconfigurable characteristic is realized by integrating three switches into the T-SIR and the PSLR. The numerical and experimental results show that the proposed antenna has a wide bandwidth ranging from 2.7 GHz to 12 GHz with voltage standing wave ratio (VSWR) less than 2, except for the two notch bands operating at 3.8-5.9 GHz and 7.7-9.2 GHz, respectively. In addition, the proposed antenna has been optimized to a compact size and can provide omnidirectional radiation patterns, which are suitable for UWB communication applications. PMID- 24222734 TI - Salinity tolerance turfgrass: history and prospects. AB - Land and water resources are becoming scarce and are insufficient to sustain the burgeoning population. Salinity is one of the most important abiotic stresses affecting agricultural productions across the world. Cultivation of salt-tolerant turfgrass species may be promising option under such conditions where poor quality water can also be used for these crops. Coastal lands in developing countries can be used to grow such crops, and seawater can be used for irrigation of purposes. These plants can be grown using land and water unsuitable for conventional crops and can provide food, fuel, fodder, fibber, resin, essential oils, and pharmaceutical products and can be used for landscape reintegration. There are a number of potential turfgrass species that may be appropriate at various salinity levels of seawater. The goal of this review is to create greater awareness of salt-tolerant turfgrasses, their current and potential uses, and their potential use in developing countries. The future for irrigating turf may rely on the use of moderate- to high-salinity water and, in order to ensure that the turf system is sustainable, will rely on the use of salt-tolerant grasses and an improved knowledge of the effects of salinity on turfgrasses. PMID- 24222735 TI - Wet chemical controllable synthesis of hematite ellipsoids with structurally enhanced visible light property. AB - A facile and economic route has been presented for mass production of micro/nanostructured hematite microcrystals based on the wet chemical controllable method. The as-prepared samples were characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and UV-Vis absorption spectroscopy. The results showed that the product was mesoporous alpha -Fe2O3 and nearly elliptical in shape. Each hematite ellipsoid was packed by many alpha -Fe2O3 nanoparticles. The values of vapor pressure in reaction systems played vital roles in the formation of porous hematite ellipsoids. Optical tests demonstrated that the micro/nanostructured elliptical hematite exhibited enhanced visible light property at room temperature. The formation of these porous hematite ellipsoids could be attributed to the vapor pressure induced oriented assembling of lots of alpha -Fe2O3 nanoparticles. PMID- 24222736 TI - The prevalence and awareness of cardiometabolic risk factors in Southern Chinese population with coronary artery disease. AB - BACKGROUND: Cardiometabolic risk factors significantly accelerate the progression of coronary artery disease (CAD); however, whether CAD patients in South China are aware of the prevalence of these risk factors is not clear yet. METHODS: The study consisted of 2312 in-admission CAD patients from 2008 to 2011 in South China. Disease history including hypertension, dyslipidemia, and diabetes was relied on patients' self-reported records. Physical and clinical examinations were tested to assess the real prevalence of the cardiometabolic risk factors. RESULTS: 57.9% of CAD patients had more than 3 cardiometabolic risk factors in terms of the metabolic syndrome. The self-known and real prevalence of hypertension, diabetes, and dyslipidemia were 56.6%, 28.3%, and 25.1% and 91.3%, 40.9%, and 92.0%, respectively. The awareness rates were 64.4%, 66.3%, and 28.5% for hypertension, diabetes, and dyslipidemia. The prevalence of cardiometabolic risk factors was significantly different among gender and among disease status. CONCLUSIONS: Most CAD patients in South China had more than three cardiometabolic risk factors. However, the awareness rate of cardiometabolic diseases was low, especially for dyslipidemia. Strategies of routine physical examination programs are needed for the early detection and treatment of cardiometabolic risk factors in order to prevent CAD progression and prognosis. PMID- 24222737 TI - Epidemiological pattern of newly diagnosed children with type 1 diabetes mellitus, Taif, Saudi Arabia. AB - INTRODUCTION AND AIM: Type-1-diabetes mellitus (T1DM) is the most commonly diagnosed type of DM in children and adolescents. We aim to identify the epidemiological profile, risk factors, clinical features, and factors related to delayed diagnosis or mismanagement in children with newly diagnosed T1DM in Taif, Saudi Arabia. PATIENTS AND METHODS: Ninety-nine newly diagnosed patients were included in the study along with 110 healthy controls. Patients were classified into 3 groups (I: >2 years, II: 2->6 years, and III: 6-12 years). Both patients and controls were tested for C-peptide, TSH, and autoantibodies associated with DM and those attacking the thyroid gland. RESULTS: Diabetic ketoacidosis was present in 79.8%. Delayed and missed diagnoses were recorded in 45.5%, with significant correlation to age and district of origin. Severity at presentation showed significant correlation with age and cow's milk feeding. Group I, those with misdiagnosis or positive DM related autoantibodies, had more severe presentations. The correlation of C-peptide and TSH levels in patients and controls was significant for C-peptide and nonsignificant for TSH. CONCLUSION: Misdiagnosis and mismanagement are common and account for more severe presentation, especially in young children >2 years. Early introduction of cow's milk appears to be a risk factor for the development of T1DM. PMID- 24222738 TI - Static testing of a bridge using an interferometric radar: the case study of "Ponte degli Alpini," Belluno, Italy. AB - Ground-based radar interferometry is an increasingly popular technique for monitoring civil infrastructures. In this paper, the static testing of a bridge is reported. It was an 8-span bridge, 297 m long, named "Ponte degli Alpini," crossing the valley of the Ardo River. The radar has been used for testing a lateral span and a central span. The obtained results present elements of novelty not previously reported in the literature. In fact, some displacement measurements of the lateral span have been affected by a horizontal shift that has to be taken into account for a correct interpretation of the measured data. Furthermore, the measurements of the central span have been carried out with the radar positioned transversally with respect to the bridge deck; this unusual arrangement has allowed for obtaining displacement maps less geometrically distorted with respect to other cases reported in the literature. PMID- 24222739 TI - Swarm intelligence and its applications. PMID- 24222740 TI - Taylor's expansion for composite functions. AB - We build a Taylor's expansion for composite functions. Some applications are introduced, where the proposed technique allows the authors to obtain an asymptotic expansion of high order in many small parameters of solutions. PMID- 24222741 TI - The efficacy of molecular markers analysis with integration of sensory methods in detection of aroma in rice. AB - Allele Specific Amplification with four primers (External Antisense Primer, External Sense Primer, Internal Nonfragrant Sense Primer, and Internal Fragrant Antisense Primer) and sensory evaluation with leaves and grains were executed to identify aromatic rice genotypes and their F1 individuals derived from different crosses of 2 Malaysian varieties with 4 popular land races and 3 advance lines. Homozygous aromatic (fgr/fgr) F1 individuals demonstrated better aroma scores compared to both heterozygous nonaromatic (FGR/fgr) and homozygous nonaromatic (FGR/FGR) individuals, while, some F1 individuals expressed aroma in both leaf and grain aromatic tests without possessing the fgr allele. Genotypic analysis of F1 individuals for the fgr gene represented homozygous aromatic, heterozygous nonaromatic and homozygous nonaromatic genotypes in the ratio 20:19:3. Genotypic and phenotypic analysis revealed that aroma in F1 individuals was successfully inherited from the parents, but either molecular analysis or sensory evaluation alone could not determine aromatic condition completely. The integration of molecular analysis with sensory methods was observed as rapid and reliable for the screening of aromatic genotypes because molecular analysis could distinguish aromatic homozygous, nonaromatic homozygous and nonaromatic heterozygous individuals, whilst the sensory method facilitated the evaluation of aroma emitted from leaf and grain during flowering to maturity stages. PMID- 24222742 TI - Shear bond strengths of different adhesive systems to biodentine. AB - The aim of this study was to measure the shear bond strength of different adhesive systems to Biodentine with different time intervals. Eighty specimens of Biodentine were prepared and divided into 8 groups. After 12 minutes, 40 samples were randomly selected and divided into 4 groups of 10 each: group 1: (etch-and rinse adhesive system) Prime & Bond NT; group 2: (2-step self-etch adhesive system) Clearfil SE Bond; group 3: (1-step self-etch adhesive systems) Clearfil S(3) Bond; group 4: control (no adhesive). After the application of adhesive systems, composite resin was applied over Biodentine. This procedure was repeated 24 hours after mixing additional 40 samples, respectively. Shear bond strengths were measured using a universal testing machine, and the data were subjected to 1 way analysis of variance and Scheffe post hoc test. No significant differences were found between all of the adhesive groups at the same time intervals (12 minutes and 24 hours) (P > .05). Among the two time intervals, the lowest value was obtained for group 1 (etch-and-rinse adhesive) at a 12-minute period, and the highest was obtained for group 2 (two-step self-etch adhesive) at a 24-hour period. The placement of composite resin used with self-etch adhesive systems over Biodentine showed better shear bond strength. PMID- 24222743 TI - Design optimization of coronary stent based on finite element models. AB - This paper presents an effective optimization method using the Kriging surrogate model combing with modified rectangular grid sampling to reduce the stent dogboning effect in the expansion process. An infilling sampling criterion named expected improvement (EI) is used to balance local and global searches in the optimization iteration. Four commonly used finite element models of stent dilation were used to investigate stent dogboning rate. Thrombosis models of three typical shapes are built to test the effectiveness of optimization results. Numerical results show that two finite element models dilated by pressure applied inside the balloon are available, one of which with the artery and plaque can give an optimal stent with better expansion behavior, while the artery and plaque unincluded model is more efficient and takes a smaller amount of computation. PMID- 24222744 TI - Effect of emitted wavelength and light guide type on irradiance discrepancies in hand-held dental curing radiometers. AB - The purpose of this study was to determine any discrepancies in the outputs of five commercial dental radiometers and also to evaluate the accuracy of these devices using a laboratory-grade spectroradiometer. The power densities of 12 different curing light sources were repeatedly measured for a total of five times using each radiometer in a random order. The emission spectra of all of the curing light sources were also measured using the spectroradiometer, and the integral value of each spectrum was calculated to determine the genuine power densities, which were then compared to the displayed power densities measured by the dental radiometers. The displayed values of power density were various and were dependent on the brand of radiometer, and this may be because each radiometer has a different wavelength sensitivity. These results cast doubt upon the accuracy of commercially available dental radiometers. PMID- 24222745 TI - An efficient method for systems of variable coefficient coupled Burgers' equation with time-fractional derivative. AB - A new homotopy perturbation method (NHPM) is applied to system of variable coefficient coupled Burgers' equation with time-fractional derivative. The fractional derivatives are described in the Caputo fractional derivative sense. The concept of new algorithm is introduced briefly, and NHPM is examined for two systems of nonlinear Burgers' equation. In this approach, the solution is considered as a power series expansion that converges rapidly to the nonlinear problem. The new approximate analytical procedure depends on two iteratives. The modified algorithm provides approximate solutions in the form of convergent series with easily computable components. Results indicate that the introduced method is promising for solving other types of systems of nonlinear fractional order partial differential equations. PMID- 24222747 TI - A higher order iterative method for computing the Drazin inverse. AB - A method with high convergence rate for finding approximate inverses of nonsingular matrices is suggested and established analytically. An extension of the introduced computational scheme to general square matrices is defined. The extended method could be used for finding the Drazin inverse. The application of the scheme on large sparse test matrices alongside the use in preconditioning of linear system of equations will be presented to clarify the contribution of the paper. PMID- 24222746 TI - Cyclin D1 G870A polymorphism and risk of nasopharyngeal carcinoma: a meta analysis. AB - Recently, there have been a number of studies on the association between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta analysis to explore more precisely the association between cyclin D1 G870A polymorphism and the risk of nasopharyngeal carcinoma. No significant association was found between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Caucasian subgroup, and no significant association in any genetic models among Asians was observed. In summary, positive results have been shown on the search for polymorphic variants influencing the risk of NPC. This meta-analysis provides evidence of the association between CCND1 G870A polymorphism and NPC risk, supporting the hypothesis that CCND1 870A allele probably acts as an important NPC protective factor in Caucasians but not in Asians. Since the results of our meta-analysis are preliminary and may be biased by the relatively small number of subjects, they still need to be validated by well-designed studies using larger samples in the future. PMID- 24222748 TI - Local gene transfer of OPG prevents joint damage and disease progression in collagen-induced arthritis. AB - This study examined the influence of osteoprotegerin (OPG) gene transfer on a murine collagen-induced arthritis model. A single periarticular injection of AAV OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks. Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P < 0.05). Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P < 0.05), although treatment appeared less effective on the local inflammatory progress. MicroCT data suggested significant protection against subchondral bone mineral density changes in OPG treated CIA mice. Interestingly, mRNA expressions of IFN-g and MMP3 were noticeably diminished following OPG gene transfer. Overall, gene transfer of OPG effectively inhibited the arthritis-associated periarticular bone erosion and preserved the architecture of arthritic joints, and the study provides evidence that the cartilage protection of the OPG gene therapy may be associated with the down-regulation of MMP3 expression. PMID- 24222749 TI - Combined effect of buoyancy force and Navier slip on MHD flow of a nanofluid over a convectively heated vertical porous plate. AB - We examine the effect of magnetic field on boundary layer flow of an incompressible electrically conducting water-based nanofluids past a convectively heated vertical porous plate with Navier slip boundary condition. A suitable similarity transformation is employed to reduce the governing partial differential equations into nonlinear ordinary differential equations, which are solved numerically by employing fourth-order Runge-Kutta with a shooting technique. Three different water-based nanofluids containing copper (Cu), aluminium oxide (Al2O3), and titanium dioxide (TiO2) are taken into consideration. Graphical results are presented and discussed quantitatively with respect to the influence of pertinent parameters, such as solid volume fraction of nanoparticles (phi), magnetic field parameter (Ha), buoyancy effect (Gr), Eckert number (Ec), suction/injection parameter (f w ), Biot number (Bi), and slip parameter ( beta ), on the dimensionless velocity, temperature, skin friction coefficient, and heat transfer rate. PMID- 24222750 TI - Plant biotechnology. PMID- 24222751 TI - Rapid synthesis of silver nanoparticles from Fusarium oxysporum by optimizing physicocultural conditions. AB - Synthesis of silver nanoparticles (SNPs) by fungi is emerging as an important branch of nanotechnology due to its ecofriendly, safe, and cost-effective nature. In order to increase the yield of biosynthesized SNPs of desired shape and size, it is necessary to control the cultural and physical parameters during the synthesis. We report optimum synthesis of SNPs on malt extract glucose yeast extract peptone (MGYP) medium at pH 9-11, 40-60 degrees C, and 190.7 Lux and in sun light. The salt concentrations, volume of filtrate and biomass quantity were found to be directly proportional to the yield. The optimized conditions for the stable and rapid synthesis will help in large scale synthesis of monodispersed SNPs. The main aim of the present study was to optimize different media, temperature, pH, light intensity, salt concentration, volume of filtrate, and biomass quantity for the synthesis of SNPs by Fusarium oxysporum. PMID- 24222752 TI - Modeling and simulation of turbulent flows through a solar air heater having square-sectioned transverse rib roughness on the absorber plate. AB - Solar air heater is a type of heat exchanger which transforms solar radiation into heat energy. The thermal performance of conventional solar air heater has been found to be poor because of the low convective heat transfer coefficient from the absorber plate to the air. Use of artificial roughness on a surface is an effective technique to enhance the rate of heat transfer. A CFD-based investigation of turbulent flow through a solar air heater roughened with square sectioned transverse rib roughness has been performed. Three different values of rib-pitch (P) and rib-height (e) have been taken such that the relative roughness pitch (P/e = 14.29) remains constant. The relative roughness height, e/D, varies from 0.021 to 0.06, and the Reynolds number, Re, varies from 3800 to 18,000. The results predicted by CFD show that the average heat transfer, average flow friction, and thermohydraulic performance parameter are strongly dependent on the relative roughness height. A maximum value of thermohydraulic performance parameter has been found to be 1.8 for the range of parameters investigated. Comparisons with previously published work have been performed and found to be in excellent agreement. PMID- 24222753 TI - Influence of root exudates on the bacterial degradation of chlorobenzoic acids. AB - Degradation of chlorobenzoic acids (e.g., products of microbial degradation of PCB) by strains of microorganisms isolated from PCB contaminated soils was assessed. From seven bulk-soil isolates two strains unique in ability to degrade a wider range of chlorobenzoic acids than others were selected, individually and even in a complex mixture of 11 different chlorobenzoic acids. Such a feature is lacking in most tested degraders. To investigate the influence of vegetation on chlorobenzoic acids degraders, root exudates of two plant species known for supporting PCB degradation in soil were tested. While with individual chlorobenzoic acids the presence of plant exudates leads to a decrease of degradation yield, in case of a mixture of chlorobenzoic acids either a change in bacterial degradation specificity, associated with 3- and 4-chlorobenzoic acid, or an extension of the spectrum of degraded chlorobenzoic acids was observed. PMID- 24222754 TI - The comparison of facial estethics between orthodontically treated patients and their parents. AB - Orthodontists emphasize the importance of facial esthetics while planning a treatment, and orthodontist state that orthodontics have more than expected effects on dentofacial esthetics. The facial esthetics of treated patients and their parents was analyzed and compared to define facial growth and to use in forensic sciences. Our study was applied to 45 orthodontic patients who were treated in our clinic and their untreated parents. The patients were divided into Classes I, II, and III groups according to their malocclusions. Pre- and posttreatment changes, pretreatment facial esthetics of the paitents and its accordance with their parents, and the calculation of heritability tests were performed. After the statistics, for pre- and posttreatment changes, all the groups except Class I revealed significant changes. There were significant correlations of patients for the heritability values and pretreatment esthetic in accordance with parents, but there were more correlations of fathers when compared to mothers. The facial esthetics in adolescences is related with so many factors, not only related with one factor. The facial esthetics in fact includes the aim of evaluation of facial properties partly or totally. Because orthodontic treatments affect facial esthetics, performing similar studies for the treatment outcomes, capabilities, and borders is important. PMID- 24222755 TI - Comparison of biofilm and attachment mechanisms of a phytopathological and clinical isolate of Klebsiella pneumoniae Subsp. pneumoniae. AB - Some bacterial species can colonize humans and plants. It is almost impossible to prevent the contact of clinically pathogenic bacteria with food crops, and if they can persist there, they can reenter the human food chain and cause disease. On the leaf surface, microorganisms are exposed to a number of stress factors. It is unclear how they survive in such different environments. By increasing adhesion to diverse substrates, minimizing environmental differences, and providing protection against defence mechanisms, biofilms could provide part of the answer. Klebsiella pneumoniae subsp. pneumoniae is clinically important and also associated with fruit diseases, such as "pineapple fruit collapse." We aimed to characterize biofilm formation and adhesion mechanisms of this species isolated from pineapple in comparison with a clinical isolate. No differences were found between the two isolates quantitatively or qualitatively. Both tested positive for capsule formation and were hydrophobic, but neither produced adherence fibres, which might account for their relatively weak adhesion compared to the positive control Staphylococcus epidermidis ATCC 35984. Both produced biofilms on glass and polystyrene, more consistently at 40 degrees C than 35 degrees C, confirmed by atomic force and high-vacuum scanning electron microscopy. Biofilm formation was maintained in an acidic environment, which may be relevant phytopathologically. PMID- 24222756 TI - Combining ability for germination traits in Jatropha curcas L. AB - Six parents of Jatropha curcas were crossed in half diallel fashion, and the F 1s were evaluated to determine the combining ability for nine germination parameters. The ratio between general combining ability (GCA) and specific combining ability (SCA) variances indicated preponderance of additive gene action for all the characters except germination percentage, time of 50% germination, seedling length, and seedling vigor index. The parents P 1 and P 2 were the best general combiner for most of the characters studied. The cross P 1 * P 5 was the best specific combiner for speed of emergence, germination percentage, germination energy, germination index, and seedling vigor index, the cross P 2 * P 5 for mean germination time, time of 50% germination, and seedling length, and the cross P 4 * P 5 for number of days to first germination. The germination percentage varied from 58.06 to 92.76% among the parents and 53.43 to 98.96% among the hybrids. The highest germination (98.96%) was observed in hybrid P 2 * P 4, and none of the hybrids or parents showed 100% germination. The highest germination index (GI) and seedling vigor index (SVI) were found in hybrid P 1 * P 5 and P 2 * P 5, respectively. The results of this study provide clue for the improvement of Jatropha variety through breeding program. PMID- 24222757 TI - Removal of Cr(VI) from aqueous environments using micelle-clay adsorption. AB - Removal of Cr(VI) from aqueous solutions under different conditions was investigated using either clay (montmorillonite) or micelle-clay complex, the last obtained by adsorbing critical micelle concentration of octadecyltrimethylammonium ions onto montmorillonite. Batch experiments showed the effects of contact time, adsorbent dosage, and pH on the removal efficiency of Cr(VI) from aqueous solutions. Langmuir adsorption isotherm fitted the experimental data giving significant results. Filtration experiments using columns filled with micelle-clay complex mixed with sand were performed to assess Cr(VI) removal efficiency under continuous flow at different pH values. The micelle-clay complex used in this study was capable of removing Cr(VI) from aqueous solutions without any prior acidification of the sample. Results demonstrated that the removal effectiveness reached nearly 100% when using optimal conditions for both batch and continuous flow techniques. PMID- 24222758 TI - Honey-induced protein stabilization as studied by fluorescein isothiocyanate fluorescence. AB - Protein stabilizing potential of honey was studied on a model protein, bovine serum albumin (BSA), using extrinsic fluorescence of fluorescein isothiocyanate (FITC) as the probe. BSA was labelled with FITC using chemical coupling, and urea and thermal denaturation studies were performed on FITC-labelled BSA (FITC-BSA) both in the absence and presence of 10% and 20% (w/v) honey using FITC fluorescence at 522 nm upon excitation at 495 nm. There was an increase in the FITC fluorescence intensity upon increasing urea concentration or temperature, suggesting protein denaturation. The results from urea and thermal denaturation studies showed increased stability of protein in the presence of honey as reflected from the shift in the transition curve along with the start point and the midpoint of the transition towards higher urea concentration/temperature. Furthermore, the increase in DeltaG D (H2O) and DeltaG D (25 degrees C) in presence of honey also suggested protein stabilization. PMID- 24222759 TI - Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging. AB - Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders. PMID- 24222760 TI - Optical Coherence Tomography Noise Reduction Using Anisotropic Local Bivariate Gaussian Mixture Prior in 3D Complex Wavelet Domain. AB - In this paper, MMSE estimator is employed for noise-free 3D OCT data recovery in 3D complex wavelet domain. Since the proposed distribution for noise-free data plays a key role in the performance of MMSE estimator, a priori distribution for the pdf of noise-free 3D complex wavelet coefficients is proposed which is able to model the main statistical properties of wavelets. We model the coefficients with a mixture of two bivariate Gaussian pdfs with local parameters which are able to capture the heavy-tailed property and inter- and intrascale dependencies of coefficients. In addition, based on the special structure of OCT images, we use an anisotropic windowing procedure for local parameters estimation that results in visual quality improvement. On this base, several OCT despeckling algorithms are obtained based on using Gaussian/two-sided Rayleigh noise distribution and homomorphic/nonhomomorphic model. In order to evaluate the performance of the proposed algorithm, we use 156 selected ROIs from 650 * 512 * 128 OCT dataset in the presence of wet AMD pathology. Our simulations show that the best MMSE estimator using local bivariate mixture prior is for the nonhomomorphic model in the presence of Gaussian noise which results in an improvement of 7.8 +/- 1.7 in CNR. PMID- 24222761 TI - Using dynamic contrast-enhanced magnetic resonance imaging data to constrain a positron emission tomography kinetic model: theory and simulations. AB - We show how dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data can constrain a compartmental model for analyzing dynamic positron emission tomography (PET) data. We first develop the theory that enables the use of DCE MRI data to separate whole tissue time activity curves (TACs) available from dynamic PET data into individual TACs associated with the blood space, the extravascular-extracellular space (EES), and the extravascular-intracellular space (EIS). Then we simulate whole tissue TACs over a range of physiologically relevant kinetic parameter values and show that using appropriate DCE-MRI data can separate the PET TAC into the three components with accuracy that is noise dependent. The simulations show that accurate blood, EES, and EIS TACs can be obtained as evidenced by concordance correlation coefficients >0.9 between the true and estimated TACs. Additionally, provided that the estimated DCE-MRI parameters are within 10% of their true values, the errors in the PET kinetic parameters are within approximately 20% of their true values. The parameters returned by this approach may provide new information on the transport of a tracer in a variety of dynamic PET studies. PMID- 24222762 TI - Impact of physical activity on cancer-specific and overall survival of patients with colorectal cancer. AB - Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial. Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords "colorectal cancer, physical activity, and survival" in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, "high" PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44-0.86). The corresponding HR OS was 0.62 (0.54-0.71). HR CSS for prediagnosis PA was 0.75 (0.62-0.91). The corresponding HR OS was 0.74 (0.62 0.89). Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk). PMID- 24222763 TI - Related Biological Research in the Interface between Bone Cement and Bone after Percutaneous Vertebroplasty. AB - Percutaneous vertebroplasty (PVP) is widely used in the treatment of painful osteoporotic vertebral compression fractures with the injection of PMMA cement, and the controversy for PMMA damage to the osteoporotic bone tissue and to affect the fractures repairing never stops. 72 old female rabbits, each age 3.0~3.5 y, rabbits were assigned randomly to two groups of thirty-six each; PMMA cement were injected into vertebral body in rabbits via mimic PVP, sacrificed at 1 h, 24 h, 3 d, 7 d, 4 w, and 12 w. The expression VEGF and collagen type I, the tissue response, and repair reaction in the interface between PMMA and bone tissue were observed dynamically with RT-PCR and western blot technique; the osteocalcin expression were studied by immunohistochemistry. Compared with the control group, the expression of collagen I increased at 1 hour and was higher from 24 h to 3 d. From 4 weeks to 12 weeks after injection of PMMA. The expression of VEGF decreased at 1 hour and 24 hours, significantly increased at 3 days, decreased once again at 7 days, then increased significantly at 4-12 weeks. The osteocalcin expression continued to increase during 4 to 12 week. PMMA would not cause local bone permanent necrosis, and interface injury repairing cycle could be prolonged in a vertebroplasty. PMID- 24222764 TI - Over time, do anthropometric measures still predict diabetes incidence in chinese han nationality population from chengdu community? AB - Objective. To examine whether anthropometric measures could predict diabetes incidence in a Chinese population during a 15-year follow-up. Design and Methods. The data were collected in 1992 and then again in 2007 from the same group of 687 individuals. Waist circumference, body mass index, waist to hip ratio, and waist to height ratio were collected based on a standard protocol. To assess the effects of baseline anthropometric measures on the new onset of diabetes, Cox's proportional hazards regression models were used to estimate the hazard ratios of them, and the discriminatory power of anthropometric measures for diabetes was assessed by the area under the receiver operating curve (AROC). Results. Seventy four individuals were diagnosed with diabetes during a 15-year follow-up period (incidence: 10.8%). These anthropometric measures also predicted future diabetes during a long follow-up (P < 0.001). At 7-8 years, the AROC of central obesity measures (WC, WHpR, WHtR) were higher than that of general obesity measures (BMI) (P < 0.05). But, there were no significant differences among the four anthropometric measurements at 15 years. Conclusions. These anthropometric measures could still predict diabetes with a long time follow-up. However, the validity of anthropometric measures to predict incident diabetes may change with time. PMID- 24222765 TI - Estrogen Induces Metastatic Potential of Papillary Thyroid Cancer Cells through Estrogen Receptor alpha and beta. AB - Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ER alpha -selective agonist), and DPN (a potent ER beta -selective agonist) on modulation of metastatic phenotype were determined by using in vitro scratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ER alpha and ER beta . E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in an in vitro experimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ER alpha and ER beta . The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9. PMID- 24222766 TI - Temperature-responsive gelation of type I collagen solutions involving fibril formation and genipin crosslinking as a potential injectable hydrogel. AB - We investigated the temperature-responsive gelation of collagen/genipin solutions using pepsin-solubilized collagen (PSC) and acid-solubilized collagen (ASC) as substrates. Gelation occurred in the PSC/genipin solutions at genipin concentrations 0-2 mM under moderate change in temperature from 25 to 37 degrees C. The PSC/genipin solutions exhibited fluidity at room temperature for at least 30 min, whereas the ASC/genipin solutions rapidly reached gel points. In specific cases PSC would be preferred over ASC as an injectable gel system. The temperature-responsive gelation of PSC/genipin solutions was due to temperature responses to genipin crosslinking and collagen fibril formation. The elastic modulus of the 0.5% PSC/genipin gel system could be adjusted in a range of 2.5 to 50 kPa by the PSC and genipin concentrations, suggesting that a PSC/genipin solution is a potential injectable gel system for drug and cell carriers, with mechanical properties matching those of living tissues. PMID- 24222767 TI - From prion diseases to prion-like propagation mechanisms of neurodegenerative diseases. AB - Prion diseases are fatal neurodegenerative sporadic, inherited, or acquired disorders. In humans, Creutzfeldt-Jakob disease is the most studied prion disease. In animals, the most frequent prion diseases are scrapie in sheep and goat, bovine spongiform encephalopathy in cattle, and the emerging chronic wasting disease in wild and captive deer in North America. The hallmark of prion diseases is the deposition in the brain of PrP(Sc), an abnormal beta -sheet-rich form of the cellular prion protein (PrP(C)) (Prusiner 1982). According to the prion hypothesis, PrP(Sc) can trigger the autocatalytic conversion of PrP(C) into PrP(Sc), presumably in the presence of cofactors (lipids and small RNAs) that have been recently identified. In this review, we will come back to the original works that led to the discovery of prions and to the protein-only hypothesis proposed by Dr. Prusiner. We will then describe the recent reports on mammalian synthetic prions and recombinant prions that strongly support the protein-only hypothesis. The new concept of "deformed templating" regarding a new mechanism of PrP(Sc) formation and replication will be exposed. The review will end with a chapter on the prion-like propagation of other neurodegenerative disorders, such as Alzheimer's and Parkinson's disease and tauopathies. PMID- 24222768 TI - In Vitro Antibacterial and Antibiotic Resistance Modifying Effect of Bioactive Plant Extracts on Methicillin-Resistant Staphylococcus epidermidis. AB - The crude extracts of plants from Asteraceae and Lamiaceae family and essential oils from Salvia officinalis and Salvia sclarea were studied for their antibacterial as well as antibiotic resistance modifying activity. Using disc diffusion and broth microdilution assays we determined higher antibacterial effect of three Salvia spp. and by evaluating the leakage of 260 nm absorbing material we detected effect of extracts and, namely, of essential oils on the disruption of cytoplasmic membrane. The evaluation of in vitro interactions between plant extracts and oxacillin described in terms of fractional inhibitory concentration (FIC) indices revealed synergistic or additive effects of plant extracts and clearly synergistic effects of essential oil from Salvia officinalis with oxacillin in methicillin-resistant Staphylococcus epidermidis. PMID- 24222769 TI - Design and Optimization of a Process for Sugarcane Molasses Fermentation by Saccharomyces cerevisiae Using Response Surface Methodology. AB - A statistical model was developed in this study to describe bioethanol production through a batch fermentation process of sugarcane molasses by locally isolated Saccharomyces cerevisiae Y-39. Response surface methodology RSM based on central composite face centered design CCFD was employed to statistically evaluate and optimize the conditions for maximum bioethanol production and study the significance and interaction of incubation period, initial pH, incubation temperature, and molasses concentration on bioethanol yield. With the use of the developed quadratic model equation, a maximum ethanol production of 255 g/L was obtained in a batch fermentation process at optimum operating conditions of approximately 71 h, pH 5.6, 38 degrees C, molasses concentration 18% wt.%, and 100 rpm. PMID- 24222770 TI - An extremely rare, remote intracerebral metastasis of oral cavity cancer: a case report. AB - Distant brain metastases from oral squamous cell carcinomas (OSCC) are extremely rare. Here we describe a case of a 53-year-old man with a primary OSCC who referred to the neurosurgical department because of epileptic seizures. MR imaging revealed an enhancing lesion in the right parietal lobe. A craniotomy with tumor removing was performed. Histopathological examination verified an invasive, minimally differentiated metastasis of the primary OSCC. The patient refused whole brain radiation therapy and died from pulmonary metastatic disease 10 months after the neurosurgical intervention without any cerebral recurrence. To the authors' knowledge, only two similar cases have been previously reported. PMID- 24222771 TI - Ciliated hepatic foregut cyst: two case reports in children and review of the literature. AB - Ciliated hepatic foregut cyst (CHFC) is a rare lesion which originates from detached hepatic diverticulum or from detachment and migration of buds from the esophageal and bronchial regions of the foregut which subsequently get entrapped by the liver during the early embryonic development of the foregut. CHFCs are mostly seen in adults and are rarely reported in children, with only about 10 cases reported in this age group. Hereby, we present two cases of CHFC in two 3.5 year-old boys; one of them had cystic lesion at medial segment of left lobe of liver (common site), and in the other one it was located at right lobe of liver (less common site). Histologically, both cysts had four layers composed of inner ciliated, pseudostratified, columnar epithelium; subepithelial connective tissue; smooth muscle layer; and an outer fibrous layer. PMID- 24222773 TI - Biodistribution of mesenchymal stem/stromal cells in a preclinical setting. AB - Due to their multi/pluripotency and immunosuppressive properties, mesenchymal stem/stromal cells (MSCs) are important tools for treatment of immune disorders and tissue repair. The increasing uses of MSCs lead to the development of production processes that need to be in accordance with good manufacturing practices (GMP). In Europe, MSCs are somatic cell-therapy products, referred to as advanced-therapy medicinal products (ATMPs), and in the United States MSCs must comply with current good tissue practice requirements. The safety and efficacy of MSCs must be ensured, whatever the cell source, and studies of dose and biodistribution are important aspects of safety testing. Preclinical data on biodistribution and pharmacodynamics are mandatory for approval. It is important to demonstrate that MSCs do not have unwanted homing that could drive to inappropriate differentiation in some organ or to support cancer development as suggested in some experiments. All these aspects should be addressed in a risk based approach according to recently published guidelines by EMA. In the present article, we summarize the main approaches for labeling and tracking of infused MSCs, report on current animal models, and give an overview of available results on biodistribution. PMID- 24222774 TI - Detecting and responding to a dengue outbreak: evaluation of existing strategies in country outbreak response planning. AB - Background. Dengue outbreaks are occurring with increasing frequency and intensity. Evidence-based epidemic preparedness and effective response are now a matter of urgency. Therefore, we have analysed national and municipal dengue outbreak response plans. Methods. Thirteen country plans from Asia, Latin America and Australia, and one international plan were obtained from the World Health Organization. The information was transferred to a data analysis matrix where information was extracted according to predefined and emerging themes and analysed for scope, inconsistencies, omissions, and usefulness. Findings. Outbreak response planning currently has a considerable number of flaws. Outbreak governance was weak with a lack of clarity of stakeholder roles. Late timing of responses due to poor surveillance, a lack of combining routine data with additional alerts, and lack of triggers for initiating the response weakened the functionality of plans. Frequently an outbreak was not defined, and early response mechanisms based on alert signals were neglected. There was a distinct lack of consideration of contextual influences which can affect how an outbreak detection and response is managed. Conclusion. A model contingency plan for dengue outbreak prediction, detection, and response may help national disease control authorities to develop their own more detailed and functional context specific plans. PMID- 24222772 TI - Perspectives on the use of stem cells for autism treatment. AB - Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. ASDs are clinically defined by deficits in communication, social skills, and repetitive and/or restrictive interests and behaviours. With the prevalence rates for ASDs rapidly increasing, the need for effective therapies for autism is a priority for biomedical research. Currently available medications do not target the core symptoms, can have markedly adverse side-effects, and are mainly palliative for negative behaviours. The development of molecular and regenerative interventions is progressing rapidly, and medicine holds great expectations for stem cell therapies. Cells could be designed to target the observed molecular mechanisms of ASDs, that is, abnormal neurotransmitter regulation, activated microglia, mitochondrial dysfunction, blood-brain barrier disruptions, and chronic intestinal inflammation. Presently, the paracrine, secretome, and immunomodulatory effects of stem cells would appear to be the likely mechanisms of application for ASD therapeutics. This review will focus on the potential use of the various types of stem cells: embryonic, induced pluripotential, fetal, and adult stem cells as targets for ASD therapeutics. PMID- 24222775 TI - Apgar score is related to development of atopic dermatitis: cotwin control study. AB - Aim. To study the impact of birth characteristics on the risk of atopic dermatitis in a twin population. Methods. In a population-based questionnaire study of 10,809 twins, 3-9 years of age, from the Danish Twin Registry, we identified 907 twin pairs discordant for parent-reported atopic dermatitis. We cross-linked with data from the Danish National Birth Registry and performed cotwin control analysis in order to test the impact of birth characteristics on the risk of atopic dermatitis. Results. Apgar score, OR (per unit) = 1.23 (1.06 1.44), P = 0.008, and female sex, OR = 1.31 (1.06-1.61), P = 0.012, were risk factors for atopic dermatitis in cotwin control analysis, whereas birth anthropometric factors were not significantly related to disease development. Risk estimates in monozygotic and dizygotic twins were not significantly different for the identified risk factors. Conclusions. In this population-based cotwin control study, high Apgar score was a risk factor for atopic dermatitis. This novel finding must be confirmed in subsequent studies. PMID- 24222776 TI - Evaluating the immunogenicity of protein drugs by applying in vitro MHC binding data and the immune epitope database and analysis resource. AB - The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic features of different prediction methods, the objective evaluation of prediction quality, and general guidelines for practical use of these tools. Finally the use, advantages, and limitations of the methodology will be demonstrated in a review of two previous studies investigating the immunogenicity of erythropoietin and timothy grass pollen. PMID- 24222777 TI - Late and chronic antibody-mediated rejection: main barrier to long term graft survival. AB - Antibody-mediated rejection (AMR) is an important cause of graft loss after organ transplantation. It is caused by anti-donor-specific antibodies especially anti HLA antibodies. C4d had been regarded as a diagnosis marker for AMR. Although most early AMR episodes can be successfully controlled or reversed, late and chronic AMR remains the leading cause of late graft loss. The strategies which work in early AMR have limited effect on late/chronic episodes. Here, we reviewed the lines of evidence that late/chronic AMR is the leading cause of late graft loss, characteristics of late AMR, and current strategies in managing late/chronic AMR. More effort should be put on the management of late/chronic AMR to make a better long term graft survival. PMID- 24222778 TI - A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells. AB - Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002) is a Taiwanese propolin G (PPG) derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 alpha (eIF2 alpha ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug. PMID- 24222779 TI - Safety and effectiveness of vibration massage by deep oscillations: a prospective observational study. AB - The objective of this study is to assess the safety of treatment with vibration massage using a deep oscillation device and the effects on symptom severity and quality of life in patients with primary fibromyalgia syndrome (FMS). Outpatients with FMS performed an observational prospective study with visits 2-4 weeks after the last treatment (control) and after further 2 months (follow-up). Patients were treated with 10 sessions of 45 min deep oscillation massage, 2/week. Primary outcome parameters were safety and tolerability (5-level Likert scale (1 = very good)) (after each treatment session and at control visit). Secondary outcome parameters were symptom severity (Fibromyalgia Impact Questionnaire (FIQ), pain) and quality of life (SF-36). Seventy patients (97.1% females) were included. At control visit, 41 patients (58.6%) reported 63 mild and short-lasting adverse events, mainly worsening of prevalent symptoms such as pain and fatigue. Tolerability was rated as 1.8 (95% confidence interval: 1.53; 2.07). Symptoms and quality of life were significantly improved at both control and follow-up visits (at least P < 0.01). In conclusion, deep oscillation massage is safe and well tolerated in patients with FMS and might improve symptoms and quality of life rather sustained. PMID- 24222781 TI - Kai-xin-san, a chinese herbal decoction containing ginseng radix et rhizoma, polygalae radix, acori tatarinowii rhizoma, and poria, stimulates the expression and secretion of neurotrophic factors in cultured astrocytes. AB - Kai-xin-san (KXS), a Chinese herbal decoction prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria. In China, KXS has been used to treat stress-related psychiatric diseases with the symptoms of depression and forgetfulness. Although animal study has supported the antidepression function of KXS, the mechanism in cellular level is still unknown. Here, a chemically standardized water extract of KXS was applied onto cultured astrocytes in exploring the action mechanisms of KXS treatment, which significantly stimulated the expression and secretion of neurotrophic factors, including NGF, BDNF, and GDNF, in a dose-dependent manner: the stimulation was both in mRNA and protein levels. In addition, the water extracts of four individual herbs did not significantly stimulate the expression of neurotrophic factors, which could explain the optimized effect of KXS in a herbal decoction. The KXS-induced expression of neurotrophic factors did not depend on signaling mediated by estrogen receptor or protein kinase. The results suggested that the antidepressant-like action of KXS might be mediated by an increase of expression of neurotrophic factors in astrocytes, which fully supported the clinical usage of this decoction. PMID- 24222782 TI - Complementary and alternative medicine for diabetes. PMID- 24222783 TI - Membership-degree preserving discriminant analysis with applications to face recognition. AB - In pattern recognition, feature extraction techniques have been widely employed to reduce the dimensionality of high-dimensional data. In this paper, we propose a novel feature extraction algorithm called membership-degree preserving discriminant analysis (MPDA) based on the fisher criterion and fuzzy set theory for face recognition. In the proposed algorithm, the membership degree of each sample to particular classes is firstly calculated by the fuzzy k-nearest neighbor (FKNN) algorithm to characterize the similarity between each sample and class centers, and then the membership degree is incorporated into the definition of the between-class scatter and the within-class scatter. The feature extraction criterion via maximizing the ratio of the between-class scatter to the within class scatter is applied. Experimental results on the ORL, Yale, and FERET face databases demonstrate the effectiveness of the proposed algorithm. PMID- 24222784 TI - Estimation of phoneme-specific HMM topologies for the automatic recognition of dysarthric speech. AB - Dysarthria is a frequently occurring motor speech disorder which can be caused by neurological trauma, cerebral palsy, or degenerative neurological diseases. Because dysarthria affects phonation, articulation, and prosody, spoken communication of dysarthric speakers gets seriously restricted, affecting their quality of life and confidence. Assistive technology has led to the development of speech applications to improve the spoken communication of dysarthric speakers. In this field, this paper presents an approach to improve the accuracy of HMM-based speech recognition systems. Because phonatory dysfunction is a main characteristic of dysarthric speech, the phonemes of a dysarthric speaker are affected at different levels. Thus, the approach consists in finding the most suitable type of HMM topology (Bakis, Ergodic) for each phoneme in the speaker's phonetic repertoire. The topology is further refined with a suitable number of states and Gaussian mixture components for acoustic modelling. This represents a difference when compared with studies where a single topology is assumed for all phonemes. Finding the suitable parameters (topology and mixtures components) is performed with a Genetic Algorithm (GA). Experiments with a well-known dysarthric speech database showed statistically significant improvements of the proposed approach when compared with the single topology approach, even for speakers with severe dysarthria. PMID- 24222785 TI - Numerical stability of partitioned approach in fluid-structure interaction for a deformable thin-walled vessel. AB - Added-mass instability is known to be an important issue in the partitioned approach for fluid-structure interaction (FSI) solvers. Despite the implementation of the implicit approach, convergence of solution can be difficult to achieve. Relaxation may be applied to improve this implicitness of the partitioned algorithm, but this commonly leads to a significant increase in computational time. This is because the critical relaxation factor that allows stability of the coupling tends to be impractically small. In this study, a mathematical analysis for optimizing numerical performance based on different time integration schemes that pertain to both the fluid and solid accelerations is presented. The aim is to determine the most efficient configuration for the FSI architecture. Both theoretical and numerical results suggest that the choice of time integration schemes has a significant influence on the stability of FSI coupling. This concludes that, in addition to material and its geometric properties, the choice of time integration schemes is important in determining the stability of the numerical computation. A proper selection of the associated parameters can improve performance considerably by influencing the condition of coupling stability. PMID- 24222788 TI - Author's reply: Use of discard pleural fluid in molecular research. PMID- 24222787 TI - The net effect: spanning diseases, crossing borders-highlights from the fourth triennial APCA conference and annual HPCA conference for palliative care. AB - The African Palliative Care Association (APCA) jointly hosted its triennial palliative care conference for Africa with the Hospice and Palliative Care Association of South Africa (HPCA) on 17-20 September 2013 in Johannesburg, South Africa. At the heart of the conference stood a common commitment to see patient care improved across the continent. The theme for the conference, 'The Net Effect: Spanning Diseases, Crossing Borders', reflected this joint vision and the drive to remember the 'net effect' of our work in palliative care-that is, the ultimate impact of the care that we provide for our patients and their families across the disease and age spectrum and across the borders of African countries. The conference, held in Johannesburg, brought together 471 delegates from 34 countries. The key themes and messages from the conference are encapsulated in ten 'C's of commitment to political will and support at the highest levels of governance; engaging national, regional, and international bodies; collaboration; diversity; palliative care for children; planning for human resources and capacity building; palliative care integration at all levels; developing an evidence base for palliative care in Africa; using new technologies; and improved quality of care. Participants found the conference to be a forum that challenged their understanding of the topics presented, as well as enlightening in terms of applying best practice in their own context. Delegates found a renewed commitment and passion for palliative care and related health interventions for children and adults with life-limiting and life-threatening illnesses within the region. This conference highlighted many of the developments in palliative care in the region and served as a unique opportunity to bring people together and serve as a lynchpin for palliative care provision and development in Africa. The delegates were united in the fact that together we can 'span diseases,' 'cross borders,' and realise the 'African Dream' for palliative care. PMID- 24222786 TI - Oestrogen receptors in breast cancer: basic mechanisms and clinical implications. AB - Since the discovery of the connection between ovarian hormones and breast cancer, endocrine therapy has been an integral adjuvant treatment for patients with hormone-dependent breast cancers. Oestrogen receptor (ER) plays a central role in mediating the effects of endogenous hormones and therapeutic agents. ER serves as a prognostic marker for responsiveness to endocrine therapy and is targeted either directly by selective oestrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block oestrogen production. A significant number of ER-positive patients, however, fail to respond to therapy or develop resistance over time. This review focuses on the current understanding of ER functions and recent advances in genomic technologies and research that have provided a global perspective on hormone and ER activity and led to a number of significant discoveries, including the roles of co regulatory factors and non-coding RNAs. Mechanistic insights into normal ER functions and therapeutic actions of SERMs and AIs will enable the development of better predictive markers and more effective target mechanisms and ultimately facilitate improvements in disease outcomes and patient survival. PMID- 24222789 TI - Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties. AB - Taking into consideration the biological activity of the only natural products containing a 1,2,4-oxadiazole ring in their structure (quisqualic acid and phidianidines A and B), the natural product analogs 1-(4-(3-tert-butyl-1,2,4 oxadiazol-5-yl)phenyl)pyrrolidine-2,5-dione (4) and 1-(4-(3-tert-butyl-1,2,4 oxadiazol-5-yl)phenyl)-1H-pyrrole-2,5-dione (7) were synthesized starting from 4 (3-tert-butyl-1,2,4-oxadiazol-5-yl)aniline (1) in two steps by isolating the intermediates 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobutanoic acid (3) and (Z)-4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobut-2 enoic acid (6). The two natural product analogs 4 and 7 were then tested for antitumor activity toward a panel of 11 cell lines in vitro by using a monolayer cell-survival and proliferation assay. Compound 7 was the most potent and exhibited a mean IC50 value of approximately 9.4 uM. Aniline 1 was synthesized by two routes in one-pot reactions starting from tert-butylamidoxime and 4 aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography. PMID- 24222790 TI - Smoking cessation in lung cancer-achievable and effective. AB - BACKGROUND: Lung cancer is the leading cause of death from cancer in Germany. 90% of cases are due to the inhalation of tobacco smoke. About 40% of patients with newly diagnosed lung cancer are still smokers. A structured smoking cessation program is medically reasonable in this situation but is only rarely offered. METHODS: This review is based on a selective search in the PubMed database combined with a manual search for current publications. RESULTS: Many cross sectional and longitudinal studies have shown that patients with lung cancer benefit from smoking cessation. After resection with curative intent, second tumors are 2.3 times more common, and recurrent tumors 1.9 times more common, in patients who continue to smoke than in those who stop. The overall mortality in smokers is 2.9 times higher. Smoking cessation also lowers the rate of radiation pneumonitis and infection during radiotherapy and prolongs the median survival after chemoradiotherapy for small-cell lung cancer (18.0 vs. 13.6 months). For patients with non-small-cell lung cancer, smoking cessation is associated with a better general state of health (77.5% vs. 57.6%). For the many patients with lung cancer who are treated palliatively, smoking cessation offers the advantages of improved pulmonary function, weight gain, and better overall quality of life. CONCLUSION: Smoking cessation in patients with lung cancer is an important means of increasing the efficacy of treatment and improving their quality of life. PMID- 24222791 TI - Control of the spread of vancomycin-resistant enterococci in hospitals: epidemiology and clinical relevance. AB - BACKGROUND: The spread of vancomycin-resistant enterococci (VRE), particularly E. faecium, in hospitals leads to many cases of colonization, but only sporadic infections. Detailed and valid risk assessment is needed so that patients at risk can be protected from VRE infection. The principal aims of risk assessment must include not only lowering VRE-associated morbidity and mortality in patients at risk, but also refraining from unnecessary anti-infective measures among those who are not at risk. METHODS: We selectively searched the PubMed database for pertinent articles on the epidemiology and clinical relevance of VRE in order to derive a uniform and practical hygiene strategy from the available scientific evidence. RESULTS: Only low-level evidence is available for the interventions studied to date, and most of the recommendations that have been issued can be characterized as expert opinion. As a rule, VRE are not highly pathogenic; they tend to have high rates of colonization, but low rates of infection. The risk factors for colonization with VRE include (among others) the administration of antibiotics and immunosuppressants, prior hospitalization, diarrhea, intubation, and other invasive treatments. The areas of highest risk are hematology/oncology wards, liver transplantation wards, dialysis units, and neonatology wards. CONCLUSION: The chain of infection can be broken by improved and consistently applied standard hygienic measures (hand and surface disinfection). Some patients are nonetheless at elevated risk of VRE infection. In specific clinical situations, the optimal protection of these patients against VRE infection demands the obligatory enforcement of stricter hygienic measures (contact isolation). PMID- 24222792 TI - Taking more time. PMID- 24222793 TI - Neuromolecular analogies. PMID- 24222794 TI - Temporal limitation and irreversibility of brain development. PMID- 24222795 TI - In reply. PMID- 24222796 TI - No indication for DSA without prior ultrasound. PMID- 24222797 TI - In reply. PMID- 24222798 TI - Methodological issues of the studies cited. PMID- 24222799 TI - Studies are carried out in hospitals. PMID- 24222800 TI - In reply. PMID- 24222801 TI - Development of a Peptide-derived orally-active kappa-opioid receptor agonist targeting peripheral pain. AB - Kappa-opioid agonists are particularly efficacious in the treatment of peripheral pain but suffer from central nervous system (CNS)-mediated effects that limit their development. One promising kappa-agonist is the peptidic compound CR665. Although not orally available, CR665 given i.v. exhibits high peripheral to CNS selectivity and benefits patients with visceral and neuropathic pain. In this study we have generated a series of derivatives of CR665 and screened them for oral activity in the acetic acid-induced rat writhing assay for peripheral pain. Five compounds were further screened for specificity of activation of kappa receptors as well as agonism and antagonism at mu and delta receptors, which can lead to off-target effects. All active derivatives engaged the kappa receptor with EC50s in the low nM range while agonist selectivity for kappa over mu or delta was >11,000-200,000-fold. No antagonist activity was detected. One compound was chosen for further analysis (Compound 9). An oral dose response of 9 in rats yielded an EC50 of 4.7 mg/kg, approaching a druggable level for an oral analgesic. To assess the peripheral selectivity of this compound an i.v. dose response in rats was assessed in the writhing assay and hotplate assay (an assay of CNS-mediated pain). The EC50 in the writhing assay was 0.032 mg/kg while no activity was detectable in the hotplate assay at doses as high as 30 mg/kg, indicating a peripheral selectivity of >900-fold. We propose that compound 9 is a candidate for development as an orally-available peripherally-restricted kappa agonist. PMID- 24222802 TI - Roles of PI3K/AKT/PTEN Pathway as a Target for Pharmaceutical Therapy. AB - Multiple enzymes participate in the phosphorylation of a group of phosphoinositide lipids. Because of their important role in signal transduction, the dysregulated metabolism of phosphoinositides represents a key step in many disease settings. Loss of their function has been demonstrated to occur as an early event a wide variety of carcinogenesis and has therefore been suggested as a biomarker for the premalignant disease. In addition, genetic alterations at multiple nodes in the pathway have been implicated in several other diseases. Accordingly, given this pervasive involvement in many diseases, the development of molecules that modulates this pathway has been initiated in studies. They have been the focus of extensive research and drug discovery activities. A better understanding of the molecular connections could uncover new targets for drug development. PMID- 24222803 TI - Nonlinear and conventional biosignal analyses applied to tilt table test for evaluating autonomic nervous system and autoregulation. AB - Tilt table test (TTT) is a standard examination for patients with suspected autonomic nervous system (ANS) dysfunction or uncertain causes of syncope. Currently, the analytical method based on blood pressure (BP) or heart rate (HR) changes during the TTT is linear but normal physiological modulations of BP and HR are thought to be predominately nonlinear. Therefore, this study consists of two parts: the first part is analyzing the HR during TTT which is compared to three methods to distinguish normal controls and subjects with ANS dysfunction. The first method is power spectrum density (PSD), while the second method is detrended fluctuation analysis (DFA), and the third method is multiscale entropy (MSE) to calculate the complexity of system. The second part of the study is to analyze BP and cerebral blood flow velocity (CBFV) changes during TTT. Two measures were used to compare the results, namely correlation coefficient analysis (nMxa) and MSE. The first part of this study has concluded that the ratio of the low frequency power to total power of PSD, and MSE methods are better than DFA to distinguish the difference between normal controls and patients groups. While in the second part, the nMxa of the three stages moving average window is better than the nMxa with all three stages together. Furthermore the analysis of BP data using MSE is better than CBFV data. PMID- 24222804 TI - Obstructive sleep apnea and metabolic syndrome in spanish population. AB - Obstructive sleep apnea (OSA) is a clinical picture characterized by repeated episodes of obstruction of the upper airway. OSA is associated with cardiovascular risk factors, some of which are components of metabolic syndrome (MS). OBJECTIVES: First, determine the prevalence of MS in patients with OSA visited in sleep clinic. Second, evaluate whether there is an independent association between MS components and the severity of OSA. METHODS: Patients with clinical suspicion of OSA were evaluated by polysomnography. Three groups were defined according to apnea hypoapnea index (AHI): no OSA (AHI <5), mild-moderate (AHI>= 5 <=30), and severe (AHI> 30). All patients were determined in fasting blood glucose, total cholesterol, HDL cholesterol, triglycerides and insulin. MS was defined according to criteria of National Cholesterol Education Program (NCEP). RESULTS: A total of 141 patients (mean age 54 +/- 11 years) were evaluated. According to AIH, 25 subjects had no OSA and 116 had OSA (41mild moderate and 75 severe). MS prevalence ranged from 43-81% in OSA group. Also, a significant increase in waist circumference, triglycerides, glucose, blood pressure levels, and a decrease in HDL cholesterol levels was observed in more severe OSA patients. All polysomnographic parameters correlated significantly with metabolic abnormalities. After a multiple regression analysis, abdominal obesity (p <0.02), glucose (p <0.01) and HDL cholesterol (p <0.001) were independently associated with OSA. CONCLUSIONS: Our findings show high prevalence of MS in OSA, especially in severe group. A significant association between OSA and some of the components of MS was found in Spanish population. PMID- 24222805 TI - Application of maldi-tof mass spectrometry in clinical virology: a review. AB - MALDI-TOF mass spectrometry is a diagnostic tool of microbial identification and characterization based on the detection of the mass of molecules. In the majority of clinical laboratories, this technology is currently being used mainly for bacterial diagnosis, but several approaches in the field of virology have been investigated. The introduction of this technology in clinical virology will improve the diagnosis of infections produced by viruses but also the discovery of mutations and variants of these microorganisms as well as the detection of antiviral resistance. This review is focused on the main current applications of MALDI-TOF MS techniques in clinical virology showing the state of the art with respect to this exciting new technology. PMID- 24222806 TI - Detection and Genotyping of Human Papillomavirus DNA in Formalin-Fixed Paraffin Embedded Specimens with the HPV Direct Flow CHIP System. AB - The novel HPV Direct Flow CHIP commercial system for Human Papillomavirus (HPV) genotyping is based on rapid PCR and automatic reverse dot blot hybridization to genotype-specific probes, allowing the detection of 36 HPV genotypes. This study examined the performance of HPV Direct Flow CHIP in formalin-fixed paraffin embedded (FFPE) samples (n= 99). Each sample was analyzed both by Direct PCR, using crude cell extracts without DNA purification, and by conventional PCR, using purified DNA. Pair-wise analysis of the results demonstrated strong concordance between the results obtained with the two protocols, although a slightly higher rate of multiple infections was detected by conventional PCR. In summary, HPV Direct Flow CHIP achieves effective HPV detection from FFPE samples with both Direct PCR and Conventional PCR protocols. PMID- 24222807 TI - Fulminant Hepatitis Due to Father-to-Newborn Transmission of Herpes Simplex Virus type 1. AB - We describe a case of a severe neonatal infection by herpes simplex virus (HSV) type 1 acquired postnatally from his father. The delivery and the first days of life were normal. He developed liver failure and disseminated intravascular coagulation when he was 19 days old. He was treated with intravenous acyclovir and the outcome was favorable. This case underlines that prevention of post-natal transmission of HSV merits to be considered in educational pregnancy programs directed at mothers and fathers. PMID- 24222809 TI - Transepithelial photorefractive keratectomy with crosslinking for keratoconus. AB - PURPOSE: To analyse visual, refractive and topographic outcomes of combining transepithelial photorefractive keratectomy (tPRK) with simultaneous corneal crosslinking for the visual rehabilitation of contact lens intolerant keratoconus patients. METHODS: Patients with topographically significant keratoconus, limited corrected vision and intolerant of contact lenses were prospectively recruited, subject to ethical approval and consent. All patients underwent single step aspheric tPRK and sequential crosslinking. Preoperative vision, refraction, corneal topography and wavefront were assessed, with postoperative assessment at 1, 3, 6, and 12 months. RESULTS: 22 eyes of 14 patients were included in the pilot study. Mean age was 32 years (SD 6.8, range 24 to 43). Mean preoperative unaided vision was 1.39 LogMAR (SD 0.5) best corrected 0.31 LogMAR (SD 0.2). Mean preoperative spherical equivalent was -2.74 Diopters (D) (SD 4.1 range -12.25 to +7.75), and mean cylinder -2.9 D (SD 1.2, range 0 to -5.5). Mean central corneal thickness was 461um (SD 29, range 411 to 516). Vision improved postoperatively; unaided 0.32 LogMAR (SD 0.4), best corrected 0.11 (SD 0.13) (P=<0.005). Mean postoperative cylinder was -1.4D (SD1.2), significantly reduced (p<0.005). Maximum keratometry (Kmax) was stable throughout postoperative follow up. (p<0.05). CONCLUSIONS: Non topographic transepithelial PRK with simultaneous crosslinking improves vision, and may offer an alternative to keratoplasty in contact lens intolerant keratoconus. Further comparative studies to topographic PRK techniques are indicated. PMID- 24222810 TI - The Effect of 3D Visual Simulator on Children's Visual Acuity - A Pilot Study Comparing Two Different Modalities. AB - PURPOSE: To evaluate the efficacy of two non-surgical interventions of vision improvement in children. METHODS: A prospective, randomized, pilot study to compare fogging method and the use of head mounted 3D display. Subjects were children, between 5 to 15 years old, with normal best corrected visual acuity (BCVA) and up to -3D myopia. Subjects played a video game as near point work, and received one of the two methods of treatments. Measurements of uncorrected far visual acuity (UCVA), refraction with autorefractometer, and subjective accommodative amplitude were taken 3 times, at the baseline, after the near work, and after the treatment. RESULTS: Both methods applied after near work, improved UCVA. Head mounted 3D display group showed significant improvement in UCVA and resulted in better UCVA than baseline. Fogging group showed improvement in subjective accommodative amplitude. While 3D display group did not show change in the refraction, fogging group's myopic refraction showed significant increase indicating the eyes showed myopic change of eyes after near work and treatment. DISCUSSION: Despite our lack of clear knowledge in the mechanisms, both methods improved UCVA after the treatments. The improvement in UCVA was not correlated to measured refraction values. CONCLUSION: UCVA after near work can be improved by repeating near and distant accommodation by fogging and 3D image viewing, although at the different degrees. Further investigation on mechanisms of improvements and their clinical significance are warranted. PMID- 24222811 TI - Nurse managers' strategies for the integration of newly graduated nurses into clinical units in Japan: a qualitative exploratory study. AB - AIM: The purpose of this study was to explore the strategies used by nurse managers in Japan to facilitate the integration of newly graduate nurses (NGNs) into their clinical units. BACKGROUND: The integration of NGNs into clinical units is an important issue for both NGNs and nurse managers because the first year of practice plays a vital role in a NGN's career. METHOD: Data were generated through semi-structured interviews with 9 nurse managers in 9 acute care hospitals. Data analysis was conducted using a qualitative content analysis method. RESULTS: Nurse managers used a total of 6 strategies: understanding the circumstances of NGNs, providing opportunities for experience and learning, supporting nurses who teach NGNs, facilitating self-learning, promoting awareness of being a nurse in the clinical unit, and strengthening the sense of comradeship in clinical units. Three of these strategies were particularly important for NGNs' integration into clinical units: facilitating self-learning, promoting awareness of being a nurse in the clinical unit, and strengthening the sense of comradeship in clinical units. These strategies were described in this study. CONCLUSIONS: The strategies adopted by nurse managers should be aimed at all nurses, not just NGNs, in order to strengthen the sense of comradeship in clinical units. This approach would create a supportive environment for the integration of NGNs into clinical units. The strategies presented in this study can be utilized not just by nurse managers but all senior nurses in the unit. NGNs can use these strategies to help them understand what they need to do to become a full member of their unit. PMID- 24222808 TI - Viral and Cellular Components of AAV2 Replication Compartments. AB - Adeno-associated virus 2 (AAV2) is a helpervirus-dependent parvovirus with a bi phasic life cycle comprising latency in absence and lytic replication in presence of a helpervirus, such as adenovirus (Ad) or herpes simplex virus type 1 (HSV-1). Helpervirus-supported AAV2 replication takes place in replication compartments (RCs) in the cell nucleus where virus DNA replication and transcription occur. RCs consist of a defined set of helper virus-, AAV2-, and cellular proteins. Here we compare the profile of cellular proteins recruited into AAV2 RCs or identified in Rep78-associated complexes when either Ad or HSV-1 is the helpervirus, and we discuss the potential roles of some of these proteins in AAV2 and helpervirus infection. PMID- 24222812 TI - An Ecological View of Internet Health Information Seeking Behavior Predictors: Findings from the CHAIN Study. AB - OBJECTIVE: The purpose of the study was to further elucidate proximal and distal demographic and social predictors of Internet Health Information Seeking Behavior (IHISB) among a cohort of HIV+ individuals through an ecological framework. METHODS: The Community Health Advisory & Information Network (CHAIN) project is an ongoing prospective study of a representative sample of persons living with HIV/AIDS in New York City and the Tri-County region. The study sample was drawn from a two-stage randomized technique with the clients of 43 medical and social service organizations with 693 HIV+ participants. Bivariate correlations were computed between IHISB and independent demographic variables in ecological blocks. Multivariate hierarchical logistic regression was used to test association between blocks of variables and IHISB. RESULTS: Among the surveyed respondents (n=645) 50.3% indicated that they used the Internet. Being above the poverty line, having less than a high school education, and having fewer neighbors were statistically significant predictors of IHISB related to HIV. CONCLUSIONS: The benefits of accessing the Internet may influence health behavior and may be considered a target for interventions that aim to increase access to health related information online. Coupled with increased access, is the need for increased patient education interventions, and creative managed care approaches to ensure that information gleaned from online sources is interpretable and accurate in order to benefit the lives of those living with HIV/AIDS. PMID- 24222813 TI - The Higher Frequency of Blood Group B in a Brazilian Population with HIV Infection. AB - OBJECTIVE: To analyze the frequency of and odds for and against HIV infection based on ABO blood type in a large sample of blood donors. BACKGROUND: Coevolution between pathogens and hosts may explain the ABO system of polymorphisms. HIV-infected cells add ABO(H) blood group antigens to the viral envelope. Naturally occurring antibodies against ABO(H) antigens that are present in normal human sera are able to neutralize ABO-expressing HIV in vitro. Blood donors are ideal for studying blood groups and HIV infection in vivo because all donors are routinely typed and tested. METHODS: All blood donors who donated blood between 1994 and 2010 were tested for HIV (ELISA antibody tests and Western blot test or immunofluorescence testing) and were ABO typed (direct and reverse grouping tests). HIV infection based on the ABO blood group was analyzed using the chi-square test and game theory. RESULTS: The total number of examined blood donors during this period was 271,410, of whom 389 were infected with HIV. B group donors were more infected than non-B donors (p= 0.006). CONCLUSIONS: A more restricted antigen recognition capacity of anti-Galalpha1-3Gal in blood groups AB and B and a weaker antigen-binding capacity of anti-A antibodies may contribute to a higher frequency of HIV infection in blood group B. PMID- 24222814 TI - Chronic vomiting and diarrhea in a young adult female. AB - PATIENT: Female, 25 FINAL DIAGNOSIS: Rumination syndrome Symptoms: Diarrhea * nausea * vomiting MEDICATION: - Clinical Procedure: - Specialty: Psychology. OBJECTIVE: Rare disease. BACKGROUND: Rumination syndrome is a behavioral disorder that consists of an effortless regurgitation of undigested food that is subsequently either re-swallowed or ejected within minutes of meal ingestion occurring with liquids and solids. It was first described in children that are mentally disadvantaged but has gained more attention to also occur among both adolescents and adults of normal mental capacity. The prevalence has never accurately been assessed due to its rarity and frequent misdiagnosis. CASE REPORT: A 25-year-old Caucasian female presented to our care with a chronic history of nausea, vomiting and diarrhea. She has vomited during the postprandial period for the last four years. She also has much as ten bouts of diarrhea per day. There is no definitive evidence of chronic laxative use or self-induced vomiting. Physical examination had no significant findings except a cachectic female patient with a BMI of 16 and hypotension. PATIENT was eventually discharged home with nutrition recommendations for nocturnal psychology follow up for relaxation behavioral techniques. CONCLUSIONS: Due to its elusiveness rumination syndrome is both underdiagnosed and a misdiagnosed condition. One of the reasons for a delayed diagnosis in patients with rumination syndrome is that many physicians are unaware of it, or are even reluctant to make this diagnosis as it could easily be confused with an eating disorder or with other gastrointestinal motility disorders. Because this syndrome may be left undiagnosed for months to years, patients often undergo many expensive and invasive procedures. PMID- 24222815 TI - Combined obstructive hypertrophic cardiomyopathy and double outlet right ventricle in an infant with Down syndrome. AB - PATIENT: Male, 2 FINAL DIAGNOSIS: Obstructive hypertrophic cardiomyopathy Symptoms: Congestive heart failure Medication: - Clinical Procedure: Left ventricular septal myectomy * repair of congenital heart disease Specialty: Cardiology. OBJECTIVE: Rare disease. BACKGROUND: Hypertrophic cardiomyopathy (HCM) is uncommon in Down syndrome (DS). When combined with congenital heart disease (CHD) both morbidity and mortality may be greater compared to CHD alone. Whether HCM in DS patients is related to having trisomy 21 versus a second site mutation is unknown. CASE REPORT: We report a case of severe HCM in an infant with DS in combination with double outlet right ventricle (DORV) who required surgery for relive of sub-aortic obstruction and congestive heart failure. We predicted that this infant would have a second site mutation involving either a sarcomeric protein or metabolic disorder as a cause for his HCM. Using current genetic and metabolic testing as well as histologic assessment of excised cardiac tissue we sought to further characterize the nature of the HCM. A successful resection of sub-aortic stenosis and DORV repair was performed. Genetic and metabolic testing was negative for gene defects and/or syndromes commonly associated with familial HCM. Excised cardiac tissue from the ventricular septum exhibited myocyte hypertrophy and sub-endocardial fibrosis but no sarcomeric disarray, myocyte fibrosis or glycogen storage. Metabolic testing for common forms of mitochondrial disease was negative. Post-operative echocardiograms show persistent, non-obstructive septal hypertrophy. CONCLUSIONS: Unlike prior reports, this child required a surgical intervention to relieve his sub-aortic obstruction. Thus, HCM in this population can be more serious that previously suspected. Although testing did not reveal the cause of his HCM, we still suggest screening for known causes of HSC until the etiology of the HCM in DS is well understood. PMID- 24222816 TI - Novel endoscopic management of a late complication following TVT insertion for stress urinary incontinence. AB - PATIENT: Female, 57 FINAL DIAGNOSIS: Bladder erosion Symptoms: Haematuria * irritative bladder symptoms * recurrent UTI Medication: - Clinical Procedure: Endoscopic tape resection Specialty: Urology. OBJECTIVE: Unusual or unexpected effect of treatment. BACKGROUND: Since 1995 over 1 million tension free vaginal slings have been utilized to treat stress incontinence. The 10 year success rates range from 84-93%. Complication rates are low by comparision. Bladder perforation occurring during the time of surgery and is managed effectively if diagnosed and treated intraoperatively. However bladder erosion occuring post-operatively predominantly occur within the first 2 years. The risk of erosion increases with body mass index and previous vaginal surgery. CASE REPORT: We report the case of a bladder erosion occurring 5 years following the original surgery. The symptoms included recurrent urinary tract infections, frequency and haematuria. A novel technique was employed using the transurethral approach to initially disintegrate the calculus and then using an endoshears to excise the mesh below the level of the epithelium. Continence was maintained postoperatively. CONCLUSIONS: This approach provides a safe alternative to both the transvaginal and transabdominal approach to excising intravesical mesh. PMID- 24222818 TI - The predictive value of transaminases at admission in patients hospitalized for heart failure: findings from the RO-AHFS registry. AB - BACKGROUND: Transaminases are commonly elevated in both the inpatient and ambulatory settings in heart failure (HF). AIMS: To determine the prevalence and degree of elevated transaminase levels at admission and to evaluate the association between transaminase levels and in-hospital morbidity and mortality. METHODS: Over a 12-month period, the Romanian Acute Heart Failure Syndromes (RO AHFS) registry enrolled consecutive patients hospitalized for HF at 13 medical centres. A post-hoc analysis of the 489 patients (15.2%) with alanine transaminase (ALT) and aspartate transaminase (AST) (upper limits of normal 31 IU/l and 32 IU/l, respectively) measured at baseline was performed. In-hospital mortality was compared across quartiles using multivariable Cox regression models. RESULTS: The prevalences of elevated ALT and AST were 28% and 24% and the medians (interquartile range) were 22 (16-47) and 23 (16-37 IU/L). Patients with elevated transaminases more commonly had right HF, cardiogenic shock, or an ejection fraction <45%. Patients with an ALT in the highest quartile were more likely to present with hypotension and a low pulse pressure, to have electrocardiographic evidence of left ventricular dyssynchrony and echocardiographic findings including increased left ventricular dimensions, reduced left ventricular ejection fraction, and valvular heart disease, to require inotropic or vasopressor support during hospitalization, and to report lower beta-blocker and angiotensin-converting enzyme inhibitor utilization. After adjusting for potential confounders, ALT was directly associated with BUN increases >=10 mg/dl, necessity for intensive care unit admission, and longer length of stay. Patients in the highest quartile of ALT experienced significantly higher rates of all-cause mortality. CONCLUSIONS: In patients hospitalized for HF, there is a graded relationship between admission transaminase levels and surrogates for in-hospital morbidity, while more pronounced elevations of ALT predict in-hospital mortality independent of known prognostic indicators. PMID- 24222819 TI - Invasive mechanical ventilation in acute coronary syndromes in the era of percutaneous coronary intervention. AB - BACKGROUND: Percutaneous coronary intervention (PCI) improves prognosis in patients with acute coronary syndromes (ACS) reducing ischaemic complications and the development of heart failure, thus potentially changing invasive mechanical ventilation (IMV) requirements. Little information exists about patients with ACS requiring IMV in the current era. We aimed to analyze IMV requirements and characteristics of ACS patients treated under current recommendations (including a high rate of PCI). METHODS: Baseline characteristics, indications for IMV, management and in-hospital and mid-term clinical course were analyzed prospectively in a consecutive series of patients with ACS admitted to a tertiary care hospital. RESULTS: We included 1821 patients, of which 106 (5.8%) required IMV. Mean follow-up was 347 days. PCI was performed in 84% of cases. Patients with IMV had more comorbidities, worse left ventricular function and more unstable hemodynamic parameters on admission. In-hospital mortality in patients requiring IMV was 29%. These patients also had higher mid-term mortality (hazard ratio (HR) 6.58; 95% confidence interval (CI) 4.49-9.64; p 0.001). The most common indication for IMV was cardiopulmonary arrest (CA) (65; 61%), followed by pulmonary oedema (27; 26%) and shock (14; 13.2%). Patients with CA were younger, with better hemodynamic parameters at admission, more favourable coronary anatomy and higher rates of PCI. There were no significant differences in overall mortality between the three groups. The main cause of death in CA patients was persistent vegetative state. CONCLUSIONS: Mortality in patients with ACS requiring IMV remained high despite a high rate of PCI. Baseline characteristics, management and clinical course were different according to the reason for IMV. The most common cause for IMV requirement was CA. PMID- 24222821 TI - A case presentation of a fatal dengue myocarditis showing evidence for dengue virus-induced lesion. AB - Dengue is a prevalent arthropod-borne viral disease in tropical and subtropical areas of the globe. Dengue clinical manifestations include asymptomatic infections; undifferentiated fever; dengue fever, which is characterized by fever, headache, retroorbital pain, myalgia, and arthralgia; and a severe form of the disease denominated dengue haemorrhagic fever/dengue shock syndrome, characterized by haemoconcentration, thrombocytopenia, and bleeding tendency. However, atypical manifestations, such as liver, central nervous system, and cardiac involvement, have been increasingly reported. We report an atypical and rare presentation of dengue disease marked by a dramatic and fatal cardiogenic shock due to acute myocarditis. Histopathological analysis of heart tissue showed several multifocal areas of muscle necrosis and intense interstitial oedema associated with clusters of virus particles inside the cardiomyocytes and in the interstitial space, providing evidence of a possible direct action of dengue virus on myocardium. PMID- 24222820 TI - Venous-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: a clinical challenge. AB - Guidelines stated that extracorporeal membrane oxygenation (ECMO) may improve outcomes after refractory cardiac arrest (CA) in cases of cardiogenic shock and witnessed arrest, where there is an underlying circulatory disease amenable to immediate corrective intervention. Due to the lack of randomized trials, available data are supported by small series and observational studies, being therefore characterized by heterogeneity and controversial results. In clinical practice, using ECMO involves quite a challenging medical decision in a setting where the patient is extremely vulnerable and completely dependent on the medical team's judgment. The present review focuses on examining existing evidence concerning inclusion and exclusion criteria, and outcomes (in-hospital and long term mortality rates and neurological recovery) in studies performed in patients with refractory CA treated with ECMO. Discrepancies can be related to heterogeneity in study population, to differences in local health system organization in respect of the management of patients with CA, as well as to the fact that most investigations are retrospective. In the real world, patient selection occurs individually within each center based on their previous experience and expertise with a specific patient population and disease spectrum. Available evidence strongly suggests that in CA patients, ECMO is a highly costly intervention and optimal utilization requires a dedicated local health-care organization and expertise in the field (both for the technical implementation of the device and for the intensive care management of these patients). A careful selection of patients guarantees optimal utilization of resources and a better outcome. PMID- 24222822 TI - Acute right ventricular failure caused by concomitant coronary and pulmonary embolism: successful treatment with endovascular coronary and pulmonary thrombectomy. AB - Patent foramen ovale (PFO) is present in approximately 25% of the general population. PFO is characterized by intermittent shunting of blood from the right to the left atrium, especially in the context of increased right-sided filling pressures, with risk of paradoxical embolism. We describe a 69-year-old woman presenting with acute chest pain, severe dyspnoea, and acute inferolateral ST segment elevation on the electrocardiogram. The patient was diagnosed with myocardial infarction and failure of the right cardiac ventricle, which was considered to be secondary to extensive pulmonary embolism leading to increased filling pressures and paradoxical coronary embolism. The patient underwent emergent percutaneous interventions with coronary thrombus extraction and pulmonary thrombus fragmentation and local thrombolysis. The patient was free of symptoms at follow up 6 months later and echocardiography showed substantially improved right ventricular function. We discuss issues related to the diagnosis, treatment, and secondary prevention for patients with concomitant pulmonary and coronary arterial thrombosis. PMID- 24222823 TI - Stress-induced cardiomyopathy (Tako-Tsubo syndrome) in Austria. AB - BACKGROUND: Tako-Tsubo syndrome (TS) is a still rarely diagnosed clinical syndrome, which is characterized by acute onset of chest pain, transient cardiac dysfunction with (frequently) reversible wall motion abnormalities (WMAs), but with no relevant obstructive coronary artery disease. METHODS AND RESULTS: Among 179 consecutive patients with proven diagnosis of TS that were retrospectively analysed in this multicentre registry, women represented the majority of patients (94%) while only 11 men (6%) developed TS. Mean age was 69.1+/-11.5 years (range 35-88 years). Cardinal symptoms of TS, which led to admission, were acute chest pain (82%) and dyspnoea (32%), respectively. All patients demonstrated typical WMAs, whereby four different types of WMAs could be defined: (1) a more common apical type of TS (n=89; 50%); (2) a combined apical and midventricular form of TS (n=23; 13%); (3) the midventricular TS (n=6; 3%); and (4) an unusual type of basal WMAs of the left ventricle (n=3). Only in 101 patients (57%), a clear causative trigger for onset of symptoms could be identified. In-hospital cardiovascular complications occurred in 25 patients (14%) and consisted of cardiac arrhythmias in 10 patients (40%), cardiogenic shock in six patients (24%), cardiac decompensation in eight patients (32%) and cardiovascular death in one patient, respectively. Echocardiographic control of left ventricular function after the initial measurement was available in almost 70% of the patients: complete recovery of WMAs was found in 73 patients (58.87%); 49 patients (39.52%) showed persistent WMAs. Recurrences of TS were only seen in four patients. During the follow-up period, 13 patients died: three of cardiovascular causes and 10 of non-cardiac causes. In-hospital mortality was 0.6%, 30-day mortality was 1.3% and 2-year mortality was 6.7%. CONCLUSIONS: This study represents to date the largest series of patients suffering from TS in Austria and worldwide. Similar to others, in our series the prevalence of TS was significantly higher in women than in men, while in contrast to other studies, the apical type of TS was detected most frequently. The similar clinical presentation of TS patients to the clinical picture of acute myocardial infarction demonstrates the importance of immediate coronary angiography for adequate differential diagnosis of TS. TS is not necessarily a benign disease due to cardiovascular complications as well as persistent WMAs with delayed recovery. PMID- 24222824 TI - Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy). AB - AIMS: The pathophysiology of apical ballooning syndrome (ABS) remains to be elucidated. The aim of this study was to evaluate the coronary vascular reactivity of patients who were previously diagnosed with ABS. METHODS AND RESULTS: A total of 228 cases of ABS were prospectively identified, and of these, 10 patients (median age 61 years (IQR 48-75); all females) who underwent coronary vasomotion testing were included in the study. Coronary epicardial and microvascular responses to intracoronary acetylcholine (ACH; % change in diameter and % change in blood flow at doses of 10(-6)-10(-4) mol/l), nitroglycerin (200 300 mg), and adenosine (36-60 ug) were evaluated. The median change in diameter with ACH was -9.3% (IQR -36.4, 3.2) with six patients (60%) demonstrating epicardial coronary constriction. The median increase in peak coronary blood flow in response to ACH was 13.1% (IQR -18.6, 55.0). This was markedly lower than the blood flow response seen in a reference group of 211 women from our laboratory (mean age 60 years) with normal microvascular responses to ACH: 103% (IQR 75, 149). Seven (70%) patients had <50% increase in coronary blood flow indicating abnormal microvascular response to ACH. 70% had either abnormal epicardial or microvascular response to ACH. Median coronary flow reserve was abnormal at 2.2% (IQR 2.0, 3.4; normal >2.5), and 90% had at least one abnormal measure of microvascular vasomotion. CONCLUSION: The novel observation is that coronary microvascular dysfunction is highly prevalent in patients with ABS. Thus, chronically impaired coronary vascular reactivity, especially involving the microcirculation, may be a central feature of the pathophysiology of ABS. PMID- 24222825 TI - Obstructive sleep apnoea increases the incidence of morning peak of onset in acute myocardial infarction. AB - AIMS: There exists a discrepancy regarding the relationship between obstructive sleep apnoea (OSA) and circadian variation during the onset of acute myocardial infarction (MI). We hypothesized that OSA patients show a characteristic circadian variation and that the severity of OSA significantly affects this variation. METHODS AND RESULTS: The present study included 288 patients with first acute MI who underwent percutaneous coronary intervention within 12 h of symptom onset. The diagnosis of OSA required an apnoea-hypopnoea index (AHI) of >=5 events/h. A total of 216 patients fulfilled the OSA criteria. The incidence of MI onset between 06:00 and 11:59 hours was significantly higher in OSA patients than in control patients (38 vs. 25%, p=0.039). Circadian variation in the morning peak of MI onset was attenuated in mild OSA (as defined by AHI, 5.0 14.9 events/h; 33 vs. 25%, p=0.240). Moderate-to-severe OSA (as defined by AHI >=15.0 events/h) clearly increased the incidence of MI onset between 06:00 and 11:59 hours (43 vs. 25%, p=0.014). Multiple logistic regression adjusting for AHI (>=15.0 events/h), age, body mass index, hypertension, and current smoking showed that moderate-to-severe OSA significantly contributed to MI onset between 06:00 and 11:59 hours (odds ratio 2.00, p=0.010). CONCLUSIONS: OSA showed a morning peak with regard to MI onset, and moderate-to-severe OSA significantly enhanced this circadian variation. PMID- 24222826 TI - Serum corin is reduced and predicts adverse outcome in non-ST-elevation acute coronary syndrome. AB - BACKGROUND AND OBJECTIVES: The aim of the current study was to describe the role of corin, an enzyme that cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide into their active peptides, in patients with acute coronary syndrome (ACS). METHODS: Serum corin level was studied in patients with non-ST elevation ACS who underwent percutaneous coronary intervention (n=152) and in control volunteers (n=103). RESULTS: The corin level was lower in acute coronary syndrome patients (798+/-288 pg/ml) than in the controls (1165+/-613 pg/ml, p<0.0001). Those acute coronary syndrome patients who developed major adverse cardiovascular events (MACE; 60.9%) within 3 years of discharge had lower corin levels than the patients who did not experience major adverse cardiovascular events (698.16+/-233.67 vs. 952.1+/-297.81 pg/ml, p<0.0001). Using a multiple logistic regression model, corin level was a significant predictor of post-ACS MACE: p=0.0004 for 50 pg/ml steps, AUC 0.791, while p<0.0001, and AUC 0.804 using corin and brain natriuretic peptide as predictors. CONCLUSIONS: Patients with non ST-elevation ACS have lower serum corin levels than controls. Corin levels are lower in ACS patients who later experience MACE and thus might be predictor for MACE. This new putative biomarker may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment and outcome prediction in ACS patients. PMID- 24222827 TI - Interhospital transfer due to failed prehospital diagnosis for primary percutaneous coronary intervention: an observational study on incidence, predictors, and clinical impact. AB - BACKGROUND: For patients with ST-elevation myocardial infarction (STEMI), guidelines recommend prehospital triage and direct referral to a percutaneous coronary intervention (PCI)-capable centre in order to minimize ischemic time. However, few have studied failed prehospital diagnosis. We assessed the incidence, predictors, and clinical impact of interhospital transfer for primary PCI after initial referral to a non-PCI-capable centre due to a failed prehospital STEMI diagnosis. METHODS: We studied 846 consecutive STEMI patients undergoing primary PCI between January 2008 and January 2010. RESULTS: We found that 609 patients (72%) were directly admitted through prehospital triage and 127 patients (15%) required interhospital transfer after failed prehospital diagnosis. Median first medical contact to treatment time was 88 min in the prehospital diagnosis group and 155 min in the interhospital transfer group (p<0.001). In the interhospital transfer group, the first available electrocardiogram was diagnostic for STEMI in 77% of cases. Predictors of interhospital transfer were female gender, diabetes, prior myocardial infarction, and greater event location to PCI-capable centre distance. Interhospital transfer independently accounted for a 47% increase in ischemic time (95% CI 33 to 63%; p<0.001). One-year mortality was higher in the interhospital transfer group (10 vs. 5.3%; p=0.030). CONCLUSIONS: Despite an often-diagnostic electrocardiogram, interhospital transfer after failed prehospital diagnosis occurred in 15% of STEMI patients undergoing primary PCI. Interhospital transfer was a major predictor of ischemic time and 1-year mortality was significantly higher. Continuing efforts to optimize prehospital triage are warranted, especially among patients at higher risk of failed prehospital diagnosis. PMID- 24222828 TI - Diagnosis and outcome in a prehospital cohort of patients with bundle branch block and suspected acute myocardial infarction. AB - BACKGROUND: Immediate revascularization is beneficial in patients with presumed new-onset bundle branch block myocardial infarction (BBBMI). In the prehospital setting, it is a challenge to diagnose new-onset BBBMI and triage accordingly. METHODS: ECG, final diagnosis, and mortality were assessed in a prehospital cohort of 4905 consecutive patients with suspected acute myocardial infarction (AMI). Bundle branch block (BBB) was defined as QRS duration >=120 ms caused by delayed intraventricular conduction. Mortality and angiography data were obtained from the Central Office of Civil Registration and the Western Denmark Heart Registry. Definite diagnosis of AMI and the onset of BBB were determined by expert consensus. Patients were divided into four groups: with or without AMI and with or without BBB. Mortality was evaluated by Kaplan-Meier plots and compared using log-rank statistics. RESULTS: AMI was diagnosed in 954 patients, of whom 118 had BBB. In 3951 patients without AMI, 436 had BBB. Patients with BBBMI were less often revascularized than patients with AMI without BBB (24 vs. 54%, p<0.001). BBBMI was categorized as new onset in 43 patients of whom two were triaged for acute angioplasty. One-year mortality was 47.2, 17.5, 20.8, and 8.6% (log-rank <0.001) in patients with BBBMI, patients with AMI without BBB, patients with BBB without AMI, and patients without AMI or BBB, respectively. CONCLUSIONS: Patients with BBBMI have a high mortality. Less than 25% undergo revascularization and only very few patients with new-onset BBBMI are transferred for urgent revascularization. Focus on improving triage and prehospital identification of high-risk patients with BBB and chest pain could improve outcome. PMID- 24222829 TI - Left bundle branch block and suspected myocardial infarction: does chronicity of the branch block matter? AB - BACKGROUND: Our aim was to investigate if patients with suspected myocardial infarction (MI) and a new or presumed new left bundle branch block (nLBBB) were treated according to the ESC reperfusion guidelines and to compare them with patients having a previously known LBBB (oLBBB). Furthermore, we investigated the prevalence of ST-segment concordance in this population. METHODS: Retrospective data was collected from the Swedeheart registry for patients admitted to the cardiac care unit at Orebro University Hospital with LBBB and suspected MI during 2009 and 2010. The patients were divided in two age groups; <80 or >=80 years and analysed for LBBB chronicity (nLBBB or oLBBB), MI, and reperfusion treatment. We also compared our data with the national Swedeheart database for 2009. RESULTS: A total of 99 patients fulfilled the inclusion criteria. A diagnosis of MI was significantly more common in the group >=80 years compared to the group <80 years (53.8 vs. 25%, p=0.007). The rate of MI was similar in the groups with nLBBB and oLBBB (33 and 37% respectively, p=0.912). Of the 36 patients with a final diagnosis of MI, only eight (22%) had nLBBB. Reperfusion treatment, defined as an acute coronary angiography with or without intervention, was significantly more often performed in patients with nLBBB compared to patients with oLBBB (42 vs. 8%, p<0.001). The rate of MI and reperfusion treatment did not differ between our institution and the Swedish national data. ST-concordance was present in only two cases, one of which did not suffer an MI. CONCLUSIONS: The proportion of patients receiving reperfusion treatment was low, but higher in nLBBB, reflecting a partial adherence to the guidelines. We found no correlation between LBBB chronicity and MI. Furthermore, only a minority of the MIs occurred in patients with nLBBB. ST-concordance was found in only one of 36 MI cases, indicating lack of sensitivity for this test. PMID- 24222830 TI - Evaluation of the diagnostic performance of current and next-generation assays for cardiac troponin I in the BWH-TIMI ED Chest Pain Study. AB - BACKGROUND: Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays. METHODS: Among patients with non-traumatic chest pain enrolled in the BWH-TIMI ED Chest Pain Study, we measured TnI (n=381) at baseline, 4-6 h, and 12-24 h with an investigational assay (S-TnI; Singulex, detection-limit 0.0002 ug/l, 99th percentile 0.009 ug/l) and a contemporary sensitive assay (TnI-Ultra; Siemens, detection-limit 0.006 ug/l, 99th percentile 0.04 ug/l). Final diagnosis was adjudicated using all diagnostic data and local hospital-based cardiac TnI (Siemens), blinded to investigational cardiac Tn. RESULTS: The adjudicated diagnosis was myocardial infarction (MI) in 96 patients, unstable angina in 41, and acute non-coronary cardiovascular conditions in 50 patients. Baseline S-TnI was highly sensitive for MI (97%, 95% CI 91-99%) with specificity 81% (95% CI 76-86%) and positive predictive value 63% (95% CI 55-71%). The negative predictive value with S-TnI was 99% (95% CI 96-100%). S-TnI had better diagnostic accuracy than the local assay (area under the curve 0.976 vs. 0.916, p=0.003). Among 20 patients with negative baseline TnI and diagnosis of MI, 19 had elevated baseline S-TnI. Compared to TnI-Ultra, S-TnI trended toward higher sensitivity (97 vs. 94%, p=NS) but did not differ significantly in negative predictive value (99 vs. 98%) or area under the curve (p=0.29). CONCLUSION: Current and investigational Tn assays substantially increased clinical sensitivity and improved diagnostic accuracy for MI, despite a decline in specificity. A contemporary sensitive assay delivered similar overall accuracy to the investigational test, suggesting that we have reached a point of maximum diagnostic return with increasing analytical sensitivity. PMID- 24222831 TI - The role of myeloperoxidase (MPO) for prognostic evaluation in sensitive cardiac troponin I negative chest pain patients in the emergency department. AB - BACKGROUND: The diagnostic work-up of patients with acute chest pain in the emergency department (ED) is a challenging task. Serial troponin testing is required to rule-out acute myocardial infarction. OBJECTIVE: To evaluate the value of myeloperoxidase (MPO) testing in sensitive cardiac troponin I (cTnI) negative patients with suspected acute coronary syndromes (ACS) in the routine setting of an ED. METHODS: MPO was assessed in 432 consecutive patients presenting to the ED with ACS. In 266 patients, serial blood samples were available. After 6 weeks, major adverse cardiac events (MACE) were assessed. MPO and cTnI were measured in all available samples. For cTnI, a sensitive assay was used. Cut-off values were derived from an independent sample of 300 healthy volunteers. RESULTS: Incidence of MACE in our population was 13%. MPO levels revealed sensitivity (Sens) of 82.1% and specificity (Spec) of 37.2% for MACE compared with 60.7% Sens and 61.4% Spec for sensitive cTnI. In serial sensitive cTnI negative patients (n=218), MACE incidence was 6.4%. MPO continued to demonstrate significant discriminatory power for the prognosis of MACE. Multivariate analyses confirmed these findings. CONCLUSION: MPO has an independent prognostic value overall and most notably in patients tested negative with a higher sensitive cardiac troponin I assay. MPO could be a promising biomarker for the initial evaluation of patients in chest pain units and is worth further investigation. PMID- 24222832 TI - FGF-23 is associated with increased disease severity and early mortality in cardiogenic shock. AB - BACKGROUND: Despite the increased use of percutaneous interventions, infarction related cardiogenic shock (CS) is still associated with high mortality. Biomarkers might be helpful to identify patients at risk, and point towards novel therapeutic strategies in CS. The phosphaturic hormone fibroblast growth factor 23 (FGF-23) has recently been introduced as a predictor for mortality in patients with chronic systolic heart failure. However, its predictive role in CS has not been investigated so far. METHODS AND RESULTS: FGF-23 was measured in 51 patients with CS. Eighteen patients with uncomplicated acute myocardial infarction (AMI) and 940 patients with stable coronary artery disease (CAD) undergoing elective coronary angiography included in a previous study served as control groups. Compared with patients with stable CAD, FGF-23 was profoundly elevated in patients with CS, but not in patients with uncomplicated AMI (CAD: 131.1 +/- 9.5; AMI: 175.3 +/- 57.2; CS: 1684.4 +/- 591.7 rU/ml, p<0.0001 CS vs. CAD). In patients with CS, FGF-23 correlated significantly with the SAPS II score (r=0.461, p=0.0003) and NT-pro BNP levels (r=0.489, p=0.001). Patients were stratified as "survivors" and "non-survivors" according to their 28-day mortality. The overall 28-day-mortality-rate was 37%. Non-survivors of CS showed significantly higher FGF-23 levels compared with survivors (3260.1 +/- 1514.7 vs. 847.9 +/- 182.4 rU/ml, p=0.028). In the ROC curve analysis, FGF-23 levels predicted 28-day mortality (area under the curve (AUC) 0.686, p=0.028), and FGF 23 level of 1180 rU/ml was identified as optimal cut-off value. In a multivariate Cox proportional hazard model adjusted for gender, blood pressure, ejection fraction and levels of creatine kinase, FGF-23 levels above 1180 rU/ml significantly predicted 28-day mortality (hazard ratio (HR) 2.74, 95% CI 1.01 7.04, p=0.037). CONCLUSION: In CS, a tremendous increase in FGF-23 occurs, and high levels of FGF-23 are associated with poor outcome. PMID- 24222833 TI - Management of acute heart failure and the effect of systolic blood pressure on the use of intravenous therapies. AB - AIMS: To examine the use of the treatments for acute heart failure (AHF) recommended by ESC guidelines in different clinical presentations and blood pressure groups. METHODS: The use of intravenous diuretics, nitrates, opioids, inotropes, and vasopressors as well as non-invasive ventilation (NIV) was analysed in 620 patients hospitalized due to AHF. The relation between AHF therapies and clinical presentation, especially systolic blood pressure (SBP) on admission, was also assessed. RESULTS: Overall, 76% of patients received i.v. furosemide, 42% nitrates, 29% opioids, 5% inotropes and 7% vasopressors, and 24% of patients were treated with NIV. Furosemide was the most common treatment in all clinical classes and irrespective of SBP on admission. Nitrates were given most often in pulmonary oedema and hypertensive AHF. Overall, only SBP differed significantly between patients with and without the studied treatments. SBP was higher in patients treated with nitrates than in those who were not (156 vs. 141 mmHg, p<0.001). Still, only one-third of patients presenting acute decompensated heart failure and SBP over 120 mmHg were given nitrates. Inotropes and vasopressors were given most frequently in cardiogenic shock and pulmonary oedema, and their use was inversely related to initial SBP (p<0.001). NIV was used only in half of the cardiogenic shock and pulmonary oedema patients. CONCLUSIONS: The management of AHF differs between ESC clinical classes and the use of i.v. vasoactive therapies is related to the initial SBP. However, there seems to be room for improvement in administration of vasodilators and NIV. PMID- 24222834 TI - The challenges in the management of right ventricular infarction. AB - In recent years, right ventricular (RV) infarction seems to be underdiagnosed in most cases of acute myocardial ischaemia despite its frequent association with inferior-wall and, occasionally, anterior-wall myocardial infarction (MI). However, its initial management is drastically different from that of left ventricular MI, and studies have indicated that RV infarction remains associated with significant morbidity and mortality, even in the mechanical reperfusion era. The pathophysiology of RV infarction involves the interaction between the right and left ventricle (LV), and the mechanism has been clarified with the advent of diagnostic non-invasive modalities, such as echocardiography and cardiac magnetic resonance. In recent years, considerable progress has been made in the treatment of RV infarction; early revascularization remains the cornerstone of the management, and fluid resuscitation, with appropriate target selection, is necessary to maintain appropriate preload. Early recognition in intensive care with clear understanding of the pathophysiology is essential to improve its prognosis. In terms of management, the support strategy for RV dysfunction is different from that for LV dysfunction since the former may often be temporary. Along with early reperfusion, maintenance of an adequate heart rate and atrioventricular synchrony are essential to sustain a sufficient cardiac output in patients with RV infarction. In refractory cases, more intensive mechanical support is required, and new therapeutic options, such as Tandem-Heart or percutaneous cardiopulmonary support systems, are being developed. PMID- 24222835 TI - Type and timing of heralding in ST-elevation and non-ST-elevation myocardial infarction: an analysis of prospectively collected electronic healthcare records linked to the national registry of acute coronary syndromes. AB - AIMS: It is widely thought that ST-elevation myocardial infarction (STEMI) is more likely to occur without warning (i.e. an unanticipated event in a previously healthy person) than non-ST-elevation myocardial infarction (NSTEMI), but no large study has evaluated this using prospectively collected data. The aim of this study was to compare the evolution of atherosclerotic disease and cardiovascular risk between people going on to experience STEMI and NSTEMI. METHODS: We identified patients experiencing STEMI and NSTEMI in the national registry of myocardial infarction for England and Wales (Myocardial Ischaemia National Audit Project), for whom linked primary care records were available in the General Practice Research Database (as part of the CALIBER collaboration). We compared the prevalence and timing of atherosclerotic disease and major cardiovascular risk factors including smoking, hypertension, diabetes, and dyslipidaemia, between patients later experiencing STEMI to those experiencing NSTEMI. RESULTS: A total of 8174 myocardial infarction patients were included (3780 STEMI, 4394 NSTEMI). Myocardial infarction without heralding by previously diagnosed atherosclerotic disease occurred in 71% STEMI (95% CI 69-72%) and 50% NSTEMI patients (95% CI 48-51%). The proportions of myocardial infarctions with no prior atherosclerotic disease, major risk factors, or chest pain was 14% (95% CI 13-16%) in STEMI and 9% (95% CI 9-10%) in NSTEMI. The rate of heralding coronary diagnoses was particularly high in the 12 months before infarct; 4.1 times higher (95% CI 3.3-5.0) in STEMI and 3.6-times higher (95% CI 3.1-4.2) in NSTEMI compared to the rate in earlier years. CONCLUSIONS: Acute myocardial infarction occurring without prior diagnosed coronary, cerebrovascular, or peripheral arterial disease was common, especially for STEMI. However, there was a high prevalence of risk factors or symptoms in patients without previously diagnosed disease. Better understanding of the antecedents in the year before myocardial infarction is required. PMID- 24222836 TI - Duration of eptifibatide infusion after percutaneous coronary intervention and outcomes among high-risk patients with non-ST-segment elevation acute coronary syndrome: insights from EARLY ACS. AB - BACKGROUND AND OBJECTIVES: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18-24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. METHODS: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10-13, 13-17, and 17-25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions. RESULTS: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI -0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI -0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10-17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups. CONCLUSIONS: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with worse ischaemic outcomes. Shorter eptifibatide infusions in this population may be feasible. PMID- 24222837 TI - Safe and feasible immediate retransfer of patients to the referring hospital after acute coronary angiography and percutaneous coronary angioplasty for patients with acute coronary syndrome. AB - BACKGROUND: The challenge with fast track (FT) is to avoid compromising medical safety. We aimed to investigate whether patients with acute coronary syndrome could be safely retransferred to the referral hospital on the same day after coronary angiography and/or percutaneous coronary angioplasty (PCI). METHODS AND RESULTS: A total of 399 consecutive patients were prospectively randomized: 206 to ordinary care (OC) and 193 to the FT group. Of these, 30% of patients were admitted for unstable angina pectoris and 70% for non-ST-segment elevation myocardial infarction. The FT patients were evaluated for possible same-day return after angiography and/or PCI. Crossover, acute, and 30-day major events were recorded. The radial approach was used in 91 and 87% in the OC and FT group, respectively. Of the FT patients, 95% were returned on the same day and nine crossover patients (4.7%) the next day or later. Major events occurred in nine patients (2.2%); five in the OC and four in the FT group. There were a total of five events within 24 hours. No events were observed during transportation and there were no early retransfers. CONCLUSIONS: Immediate written reports and good communication with the referring hospital enabled thoroughly selected patients to be safely returned on the same day as angiography and/or PCI. PMID- 24222838 TI - Early discharge after primary percutaneous coronary intervention for ST-elevation myocardial infarction. AB - BACKGROUND: To assess safety of early discharge following primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Retrospective analysis of prospectively collected data of 2448 STEMI patients treated with PPCI surviving to hospital discharge. Post discharge all-cause mortality was reported at 1, 7, and 30 days and long-term follow up. A total of 1542 patients (63.0%) were discharged within 2 days of admission (early discharge group) and 906 patients (37.0%) after 2 days (late discharge group). In both groups, no deaths were recorded 1 day post discharge. The early and late discharge group mortality figures for 7 days were 0 and 4 patients (0.04%) and between 7 and 30 days were 11 (0.7%) and 11 patients (1.2%), respectively. During a mean follow up of 584 days, 178 patients (7.3%) died: 67 in the early discharge group (4.3%) and 111 in the late discharge group (12.3%). CONCLUSIONS: This exploratory, observational study demonstrates that discharging low-risk STEMI patients within 2 days following PPCI is safe. For providers of health care, early discharge can help to allay the cost of providing a 24-hour PPCI service and adds to the recognized benefits arising from PPCI. PMID- 24222839 TI - Safety of intravenous ivabradine in acute ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention: a randomized, placebo-controlled, double-blind, pilot study. AB - AIMS: Rapid heart rate lowering may be attractive in acute ST-segment elevation myocardial infarction (STEMI). Accordingly we studied the effect of intravenous ivabradine on heart rate in this setting. METHODS AND RESULTS: This was a multicenter randomized double-blind placebo-controlled trial: patients aged 40-80 years were randomized after successful primary percutaneous coronary intervention (PCI) performed within 6 h of STEMI symptom onset. Patients were in sinus rhythm and with heart rate >80 bpm and systolic blood pressure >90 mm Hg. They were randomly assigned (2:1 ratio) to intravenous ivabradine (n=82) (5 mg bolus over 30 s, followed by 5 mg infusion over 8 h) or matching placebo (n=42). The primary outcome measure was heart rate and blood pressure. In both groups, heart rate was reduced over 8 h, with a faster and more marked decrease on ivabradine than placebo (22.2 +/- 1.3 vs 8.9 +/- 1.8 bpm, p<0.0001). After treatment discontinuation, heart rate was similar in both groups. Throughout the study, there was no difference in blood pressure between groups. There was no difference in cardiac biomarkers (creatine kinase (CK-MB), troponin T and troponin I). On echocardiography performed at baseline and post treatment (median 1.16 days), final left ventricular volumes were lower in the ivabradine group both for left ventricular end-diastolic volume (LVEDV) (87.1 +/- 28.2 vs 117.8 +/- 21.4 ml, p=0.01) and left ventricular end-systolic volume (LVESV) (42.5 +/- 19.0 versus 59.1 +/- 11.3 ml, p=0.03) without differences in volume change or left ventricular ejection fraction. CONCLUSION: This pilot study shows that intravenous ivabradine may be used safely to slow the heart rate in STEMI. Further studies are needed to characterize its effect on infarct size, left ventricular function and clinical outcomes in this population. PMID- 24222842 TI - Hypothermic Machine Perfusion Preservation of the DCD Kidney: Machine Effects. AB - Purpose. Kidneys from DCD donors represent a significant pool, but preservation problems exist. The study objective was to test the importance of machine type for hypothermic preservation of DCD kidneys. Methods. Adult Beagle dog kidneys underwent 45 minutes of warm in situ ischemia followed by hypothermic perfusion for 24 hours (Belzer-MPS Solution) on either an ORS LifePort or a Waters RM3 using standard perfusion protocols. Kidneys were then autotransplanted, and renal function was assessed over 7 days following contralateral nephrectomy. Results. Renal vascular resistance was not different between the two pumps. After 24 hours, the oxygen partial pressure and oxygen delivery in the LifePort perfusate were significantly lower than those in the RM3 but not low enough to change lactate production. TheLifePort ran significantly colder than RM3 (2 degrees versus 5 degrees C). The arterial pressure waveform of the RM3 was qualitatively different from the waveform of the LifePort. Preservation injury after transplantation was not different between the devices. When the LifePort was changed to nonpulsatile flow, kidneys displayed significantly greater preservation injury compared to RM3. Conclusions. Both LifePort and RM3 can be used for hypothermic machine perfusion preservation of DCD kidneys with equal outcomes as long as the duty cycle remains pulsatile. PMID- 24222843 TI - Cellular debris in the anterior vitreous in silent eyes of behcet patients as a clue of asymptomatic ocular involvement. AB - Purpose. To investigate if there is a prognostic implication of the presence of cellular debris in the anterior vitreous in patients with Behcet's disease (BD) without any ocular symptoms. Methods. One hundred and twenty eyes of 60 patients with BD were included in the study. The eyes were divided into two groups according to the presence of cellular debris in the anterior vitreous. The first group included 54 eyes which were cellular debris (+) (group A), and the second group included 66 eyes which were cellular debris (-) (group B). Fluorescein angiography (FA) was performed to all patients following routine ocular examination. Patients were called for the six monthly control visits to investigate possible new ocular involvement during followup. The Kaplan-Meier method was used to estimate survival curves. Results. Seven eyes (13%) in group A and four eyes (6.1%) in group B showed optic disc hyperfluorescence on FA (P = 0.2). None of the eyes with disc hyperflourescence on initial examination developed uveitis attacks in their followup. In Kaplan-Meier survival analysis there was a significant difference between the groups (group A 20.6% and group B 4.2%) by means of ocular involvement during their followup (log-rank = 6.85, P = 0.009). Conclusions. Presence of cellular debris in the anterior vitreous may have prognostic implications in patients with BD screened for ocular involvement. PMID- 24222840 TI - Management and outcomes of patients presenting with STEMI by use of chronic oral anticoagulation: results from the GRACE registry. AB - AIMS: To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy. METHODS: Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models. RESULTS: Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, p<0.001) and atrial fibrillation (32 and 22%, p=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization. CONCLUSIONS: This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline indicated management, but have similar adjusted rates of in-hospital and 6-month mortality. PMID- 24222844 TI - (R)- alpha -Aminoadipic Acid: A Versatile Precursor for the Synthesis of D-Amino Acids. AB - The ready accessibility of (R)- alpha -aminoadipic acid by enzymatic cleavage of cephalosporin C (CephC) in the production of 7-aminocephalosporanic acid (7-ACA) on a large scale makes it a favorable chiral pool building block for the synthesis of unusual amino acids. A route for the synthesis of C-5-alkenyl and C 6-alkylidene derivatives of (R)-pipecolic acid is described which utilizes (R)- alpha -aminoadipic acid as the enantiomerically pure starting material. Moreover, the synthesis of azido and triazolyl derivatives of (R)- alpha -aminoadipic acid is reported. PMID- 24222845 TI - DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-derived DNA adduct, heptanone-etheno-2'-deoxycytidine. AB - Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2' deoxyguanosine (8-oxo-dG), 1,N(6)-etheno-2'-deoxyadenosine ( epsilon dA), and heptanone-etheno-2'-deoxycytidine (H epsilon dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H epsilon dC in RA were significantly higher (P < 0.0001) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and epsilon dA accumulation between RA patients and controls. H epsilon dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H epsilon dC may have some influence on the development of RA and/or its complications. PMID- 24222846 TI - Determinants of Tuberculosis Infection among Adult HIV Positives Attending Clinical Care in Western Ethiopia: A Case-Control Study. AB - There has been a drastic rise of tuberculosis (TB) infection across the world associated with the pandemic occurrence of HIV/AIDS. There are various determinants factors that increase the chance of TB infection among HIV positives (TB/HIV confection) that varies contextually. This study aimed to assess the determinants of TB/HIV coinfection among adult HIV positives attending clinical care at two public health facilities in Nekemte, western Ethiopia. Unmatched case control study was conducted from December 26, 2011, to February 29, 2012. Cases were 123 TB infected HIV positives, and controls were 246 non-TB infected HIV positives. Being divorced/widowed AOR = 3.02, 95% CI (1.70, 7.88), not attending formal education AOR = 4.32, 95% CI (2.20, 14.15), being underweight (BMI < 18.5 kg/m(2)) AOR = 3.87, 95% CI (2.18, 6.87), having history of diabetic mellitus AOR = 3.63, 95% CI (1.33, 9.94), and being in advanced WHO HIV/AIDS clinical staging AOR = 2.29, 95% CI (1.32, 3.98), were determinant factors associated with TB/HIV co-infection. Having a separate kitchen AOR = 0.48, 95% CI (0.28, 0.81) showed protective role. For most of these determinants interventions can be made at individual and institutional levels, whereas, factors like education and nutrition need societal level integrations. PMID- 24222847 TI - Functionally defective high-density lipoprotein and paraoxonase: a couple for endothelial dysfunction in atherosclerosis. AB - The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL's inductive effects and avoiding the ox-LDL's inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. "Healthy HDL," namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. "Dysfunctional HDL," on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future. PMID- 24222848 TI - Correlates of Caregiver Burden among Family Members of Patients with Schizophrenia in Lagos, Nigeria. AB - Family members of patients with schizophrenia have enormous roles in the care of their patients, which could negatively impact their well being. Development of interventions targeted at alleviating the burden of informal care giving is hinged on the recognition of the factors associated with the various dimensions of burden. This study determined the correlates of caregiver burden among family members of patients with schizophrenia in Lagos, Nigeria. The study instruments included the Zarit burden interview (ZBI) and the positive and negative syndrome scale for schizophrenia (PANSS). Exploratory factor analysis of the ZBI produced a five-factor structure with "financial/physical strain", "time/dependence strain", "emotional strain", "uncertainty", and "self-criticism" domains. On multiple regression analyses, total PANSS scores, poor social support, and lower educational levels of caregivers were predictive of higher burden scores on the "financial/physical strain", "time/dependence", and "emotional strain" domains. Longer duration of illness, shorter patient-caregiver contact time, and being a female caregiver were predictive of higher burden scores on the "uncertainty", "self-criticism", and "emotional strain" domains, respectively. There is need for interventions to alleviate the burden on caregivers of patients with schizophrenia in Nigeria. These strategies must include comprehensive social support and improve access to services for patients and their caregivers. PMID- 24222849 TI - Treatment engagement of psychotic patients with a mobile mental health unit in rural areas in Greece: a five-year study. AB - Objectives. Treatment of psychotic disorders is impended by high rates of disengagement from mental health services and poor adherence to antipsychotic medication. This study examined the engagement rates of psychotic patients with a community mental health service during a 5-year period. Methods. The Mobile Mental Health Unit of Ioannina and Thesprotia (MMHU I-T) delivers services in remote, rural, mountainous areas using the resources of the primary care system. Clinical and demographic information for patients with a diagnosis of schizophrenia and related psychoses was obtained from the medical records of our unit. Results. A total of 74 psychotic patients initially engaged in treatment with our unit. In half of cases treatment was home-based. With the exclusion of patients who died or discharged, engagement rates were 67.2%. Statistical analysis was performed for 64 patients, and no differences were found between engaged and disengaged patients regarding clinical and demographic parameters. All engaged patients regularly refilled their antipsychotic prescriptions. Conclusion. Engagement rates in our study were comparable to previous research, involving urban settings and shorter follow-up duration. Community mental health teams may ensure treatment continuation for psychotic patients in deprived, remote areas. This is important for low-income countries, affected by economic crisis, such as Greece. PMID- 24222850 TI - The Human Urinary Proteome Fingerprint Database UPdb. AB - The use of human urine as a diagnostic tool has many advantages, such as ease of sample acquisition and noninvasiveness. However, the discovery of novel biomarkers, as well as biomarker patterns, in urine is hindered mainly by a lack of comparable datasets. To fill this gap, we assembled a new urinary fingerprint database. Here, we report the establishment of a human urinary proteomic fingerprint database using urine from 200 individuals analysed by SELDI-TOF (surface enhanced laser desorption ionisation-time of flight) mass spectrometry (MS) on several chip surfaces (SEND, HP50, NP20, Q10, CM10, and IMAC30). The database currently lists 2490 unique peaks/ion species from 1172 nonredundant SELDI analyses in the mass range of 1500 to 150000. All unprocessed mass spectrometric scans are available as ".xml" data files. Additionally, 1384 peaks were included from external studies using CE (capillary electrophoresis)-MS, MALDI (matrix assisted laser desorption/ionisation), and CE-MALDI hybrids. We propose to use this platform as a global resource to share and exchange primary data derived from MS analyses in urinary research. PMID- 24222851 TI - Nutritional and functional assessment of hospitalized elderly: impact of sociodemographic variables. AB - Background. This work was constructed in order to assess the nutritional and functional status in hospitalized elderly and to study the associations between them and sociodemographic variables. Methods. 200 elderly patients (>65 years old) admitted to Internal Medicine and Neurology Departments in nonemergency conditions were included. Comprehensive geriatric assessments, including nutritional and functional assessments, were done according to nutritional checklist and Barthel index, respectively. Information was gathered from the patients, from the ward nurse responsible for the patient, and from family members who were reviewed. Results. According to the nutritional checklist, 56% of participants were at high risk, 18% were at moderate risk of malnutrition, and 26% had good nutrition. There was a high nutritional risk in patients with low income and good nutrition in patients with moderate income. Also, there was a high nutritional risk in rural residents (61.9%) in comparison with urban residents (25%). Barthel index score was significantly lower in those at high risk of malnutrition compared to those at moderate risk and those with good nutrition. Conclusions. Hospitalized elderly are exposed to malnutrition, and malnourished hospitalized patients are candidates for functional impairment. Significant associations are noticed between both nutritional and functional status and specific sociodemographic variables. PMID- 24222852 TI - The Use of Multiple Correspondence Analysis to Explore Associations between Categories of Qualitative Variables in Healthy Ageing. AB - The main focus of this study was to illustrate the applicability of multiple correspondence analysis (MCA) in detecting and representing underlying structures in large datasets used to investigate cognitive ageing. Principal component analysis (PCA) was used to obtain main cognitive dimensions, and MCA was used to detect and explore relationships between cognitive, clinical, physical, and lifestyle variables. Two PCA dimensions were identified (general cognition/executive function and memory), and two MCA dimensions were retained. Poorer cognitive performance was associated with older age, less school years, unhealthier lifestyle indicators, and presence of pathology. The first MCA dimension indicated the clustering of general/executive function and lifestyle indicators and education, while the second association was between memory and clinical parameters and age. The clustering analysis with object scores method was used to identify groups sharing similar characteristics. The weaker cognitive clusters in terms of memory and executive function comprised individuals with characteristics contributing to a higher MCA dimensional mean score (age, less education, and presence of indicators of unhealthier lifestyle habits and/or clinical pathologies). MCA provided a powerful tool to explore complex ageing data, covering multiple and diverse variables, showing if a relationship exists and how variables are related, and offering statistical results that can be seen both analytically and visually. PMID- 24222853 TI - Epicardial coronary arteries in khat chewers presenting with myocardial infarction. AB - Background. Khat chewing is a common habit in Yemen despite increased evidence of its negative impact on the cardiovascular system. Aims. We aimed to study the epicardial coronary arteries in khat chewers presenting with myocardial infarction (AMI). Materials and Methods. A descriptive, cross-sectional study was conducted between November 2008 and May 2009 in Yemen. AMI patients who underwent coronary angiogram were enrolled and divided into groups (gp): gp1 (diabetic and khat chewers), gp2 (khat chewers and nondiabetic), and gp3 (diabetic and non-khat users). Results. Of 347 AMI patients 63%, 21%, and 16% were in gp 2, 3, and 1, respectively. Khat chewers were younger in comparison to non-khat users. Group 3 patients were more likely to have multivessel disease, severe left anterior descending (LAD), right coronary artery (RCA) stenosis and total RCA, and left circumflex (Lcx) occlusion compared to other groups. Group 1 patients were more likely to have total LAD occlusion and severe Lcx lesions. In multivariate analysis, age, diabetes mellitus, and smoking were significant independent predictors for significant coronary artery lesions; however, khat chewing did not show such association. Conclusions. Coronary spasm is the main mechanism of AMI in khat chewers. The impact of our finding for risk stratification and management warrants further studies. PMID- 24222854 TI - Nonconcordance between Clinical and Head CT Findings: The Specter of Overdiagnosis. AB - Background. It is unclear whether history and physical examination findings can predict abnormalities on head computed tomography (CT) believed to indicate increased risk of lumbar-puncture- (LP-) induced brain herniation. The objectives of this study were to (1) identify head CT findings felt to be associated with increased risk of brain herniation and (2) to assess the ability of history and physical examination to predict those findings. Methods. Using a modified Delphi survey technique, an expert panel defined CT abnormalities felt to predict increased risk of LP-induced brain herniation. Presence of such findings on CT was compared with history and physical examination (H&P) variables in 47 patients. Results. No H&P variable predicted "high-risk" CT; combining H&P variables to improve sensitivity led to extremely low specificity and still failed to identify all patients with high-risk CT. Conclusions. "High-risk" CT is not uncommon in patients with clinical characteristics known to predict an absence of actual risk from LP, and thus it may not be clinically relevant. "Overdiagnosis" will be increasingly problematic as technological advances identify increasingly subtle deviations from "normal." PMID- 24222855 TI - Interrater Reproducibility of Knee Movement Analyses during the Stance Phase: Use of Anatomical Landmark Calibration with a Rigid Marker Set. AB - Objective. Measurements of knee joint movement in gait analysis may result in large errors caused by misplacement of reflective markers by the testers. To properly understand the measurement results, it is important to guarantee the reliability of the measurement method used for the purpose. The aim of this study was to confirm the interrater reproducibility of a measurement method with a rigid marker set (RMS). Methods. The study subjects were four healthy adults, and the testers were three physical therapists. The interrater reproducibility of the measurements was verified by using the coefficient of multiple correlations (CMCs) and the standard error of measurement (SEM). Results. The average CMCs values of 4 subjects in knee joint movement at the stance phase were greater than 0.8, and the average SEM values of 4 subjects in knee joint movement at the stance phase were also relatively good (maximum error: 2.42 degrees ). Conclusion. Based on these results, the measurement method with estimation of anatomical landmarks using the RMS can prevent misplacement during attachment of the reflective markers, as long as the testers have sufficient experience in attaching reflective markers. PMID- 24222856 TI - Identification of DLEC1 D215N Somatic Mutation in Formalin Fixed Paraffin Embedded Melanoma and Melanocytic Nevi Specimens. AB - DLEC1 has been suggested as a tumor suppressor gene in several cancers. DLEC1 D215N somatic mutation (COSM36702) was identified in a melanoma cell line through whole genome sequencing. However, little is known about the implication and prevalence of this mutation in primary melanomas or in melanocytic nevi. The aim of this study was to genotype DLEC1 D215N mutation in melanoma tissue and melanocytic nevi samples to confirm its occurrence and to estimate its prevalence. Primary melanomas (n = 81) paired with synchronous or asynchronous metastases (n = 21) from 81 melanoma patients and melanocytic nevi (n = 28) were screened for DLEC1 D215N mutation. We found the mutation in 3 primary melanomas and in 2 melanocytic nevi, corresponding to a relatively low prevalence (3.7% and 7.1%, resp.). The pathogenic role of DLEC1 215N mutation is unclear. However, since the mutation has not been previously described in general population, its involvement in nevogenesis and melanoma progression remains a possibility to be clarified in future studies. PMID- 24222857 TI - Simulation of Drug Release from PLGA Particles In Vivo. AB - Specific targeting of tissues and/or cells is essential for any type of drug delivery system because this determines the efficacy and side effects of the drug. Poly lactic-co-glycolic acids (PLGA) have long been used as biomaterials for drug delivery due to their excellent biocompatibility and biodegradability. Direct visualization of PLGA particles is feasible even within tissues, and cell specificity of the drug delivery system is normally assessed by using labeled particles. However, particle labeling alone does not address factors such as the release and distribution of the drug. Thus, it is desirable to set up a simulation system of drug release and distribution in vivo. In the present study, we aimed to establish a method to simulate drug distribution in PLGA drug delivery by using Hoechst 33342 as an imitating drug. Our approach enabled us to identify, isolate, and characterize cells exposed to Hoechst 33342 and to deduce the concentration of this fluorescent dye around both targeted and nontargeted cells. We believe that the method described herein will provide essential information regarding the specificity of cell targeting in any type of PLGA drug delivery system. PMID- 24222858 TI - Development of dorzolamide loaded 6-o-carboxymethyl chitosan nanoparticles for open angle glaucoma. AB - Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and (13)C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55 degrees C. The FT-IR, DSC and (13)C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 +/- 2.62 nm and +33.47 +/- 0.723 mV, whereas those for OCM-CSNPs were 187.1 +/- 2.72 nm and 30.87 +/- 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment. PMID- 24222859 TI - Association of RXR-Gamma Gene Variants with Familial Combined Hyperlipidemia: Genotype and Haplotype Analysis. AB - Background. Familial combined hyperlipidemia (FCHL), the most common genetic form of hyperlipdemia, is characterized by a strong familial clustering and by premature coronary heart disease. The FCHL locus has been mapped to human chromosome 1q21-q23. This region includes the retinoid X receptor gamma (RXRG), a nuclear factor member of the RXR superfamily, which plays important roles in lipid homeostasis. Objective. To investigate the possible role of the RXRG gene in the genetic susceptibility to FCHL. Methods. Variations in RXRG gene were searched by direct sequencing, and the identified SNPs were genotyped by PCR-RFLP in 192 FCHL individuals from 74 families and in 119 controls. Results. We identified 5 polymorphisms in the RXRG gene (rs1128977, rs2651860, rs2134095, rs283696, and rs10918169). Genotyping showed that the A-allele of rs283696 SNP was significantly associated with FCHL (corrected P, P c < 0.01). Also the alleles of the rs10918169 and of the rs2651860 SNP were more frequent in FCHL subjects compared to those in controls, although not significantly after correction. When the clinical characteristics of the FCHL subjects were stratified by allele carrier status for each SNP, the rs2651860 SNP was significantly associated with increased levels of LDL-cholesterol and of Apo-B in T-allele carriers (P < 0.04). Finally, haplotypes analysis with all 5 SNPs confirmed the significant association of RXRG gene with FCHL. Specifically, the haplotype containing all 3 "at-risk" alleles, significantly associated with FCHL (A-allele of rs283696, G-allele of rs10918169, and T-allele of rs2651860), showed an OR (Odds Ratio) of 2.02, P c < 0.048. Conversely, the haplotype without all these 3 alleles was associated with a reduced risk for FCHL (OR = 0.39, P c < 0.023). The "at-risk" haplotype CTTAG was also associated with higher LDL-C (P < 0.015). In conclusion, variation in the RXRG gene may contribute to the genetic dyslipidemia in FCHL subjects. PMID- 24222860 TI - Quantifying the ki-67 heterogeneity profile in prostate cancer. AB - BACKGROUND: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied. METHODS: Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67. RESULTS: Interprostatic Ki-67 mean +/- standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 +/- 3.8%, 7.4 +/- 6.8%, and 12.0 +/- 12.4% (ANOVA P = 0.013). Intraprostatic mean +/- SD Ki-67 ranges in L, I, and H risk patients were 2.6 +/- 3.6%, 5.3 +/- 6.8%, and 10.9 +/- 12.3% (ANOVA P = 0.027). Intralesion mean +/- SD Ki-67 ranges in L, I, and H risk patients were 1.1 +/- 0.9%, 5.2 +/- 7.9%, and 8.1 +/- 10.8% (ANOVA P = 0.22). ADC values at Ki-67 > and <7.1% were 860 +/- 203 and 1036 +/- 217, respectively (P = 0.0029). CONCLUSIONS: High risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki 67 clinically. PMID- 24222862 TI - Recent developments in liposome-based veterinary therapeutics. AB - Recent advances in nanomedicine have been studied in the veterinary field and have found a wide variety of applications. The past decade has witnessed a massive surge of research interest in liposomes for delivery of therapeutic substances in animals. Liposomes are nanosized phospholipid vesicles that can serve as delivery platforms for a wide range of substances. Liposomes are easily formulated, highly modifiable, and easily administered delivery platforms. They are biodegradable and nontoxic and have long in vivo circulation time. This review focuses on recent and ongoing research that may have relevance for veterinary medicine. By examining the recent developments in liposome-based therapeutics in animal cancers, vaccines, and analgesia, this review depicts the current significance and future directions of liposome-based delivery in veterinary medicine. PMID- 24222863 TI - Calotropis procera Root Extract Has the Capability to Combat Free Radical Mediated Damage. AB - The present study reports the antioxidant and membrane protective activities of Calotropis procera aqueous root extract using several in vitro assays along with the determination of phenolic as well as flavonoid contents. Total phenol and flavonoid contents in extract were 15.67 +/- 1.52 mg propyl gallate equivalent/g and 1.62 +/- 0.05 mg quercetin equivalent/g, respectively. UV-visual spectroscopic scanning of the extract indicated the presence of glycoside-linked tannins or flavonoids. The extract exhibited appreciable reducing power signifying hydrogen donating potential. DPPH radical scavenging assay revealed substantial free radical scavenging activity (42-90%) in the extracts. Concentration dependent response was observed in the metal ion chelating activity (16-95%). Extracts also provided protection against iron induced lipid peroxidation in rat tissue (liver, brain, and kidney) homogenates. Comparatively better protective efficacy against peroxidative damage was observed in liver (71%) followed by kidney (65%) and brain (60%) tissues. Positive correlation (r (2) = 0.756) was observed between DPPH free radical scavenging activity and reducing power of extract. Similarly strong positive correlation (r (2) ~ 0.756) was observed between metal ion chelating ability and percentage lipid peroxidation inhibition in different tissues. The study demonstrated considerable protective efficacy in C. procera root aqueous extracts against free radical and metal ion mediated oxidative damage. PMID- 24222861 TI - The modern primitives: applying new technological approaches to explore the biology of the earliest red blood cells. AB - One of the most critical stages in mammalian embryogenesis is the independent production of the embryo's own circulating, functional red blood cells. Correspondingly, erythrocytes are the first cell type to become functionally mature during embryogenesis. Failure to achieve this invariably leads to in utero lethality. The recent application of technologies such as transcriptome analysis, flow cytometry, mutant embryo analysis, and transgenic fluorescent gene expression reporter systems has shed new light on the distinct erythroid lineages that arise early in development. Here, I will describe the similarities and differences between the distinct erythroid populations that must form for the embryo to survive. While much of the focus of this review will be the poorly understood primitive erythroid lineage, a discussion of other erythroid and hematopoietic lineages, as well as the cell types making up the different niches that give rise to these lineages, is essential for presenting an appropriate developmental context of these cells. PMID- 24222864 TI - Age-associated reduction of asymmetry in human central auditory function: a 1H magnetic resonance spectroscopy study. AB - The aim of this study was to investigate the effects of age on hemispheric asymmetry in the auditory cortex after pure tone stimulation. Ten young and 8 older healthy volunteers took part in this study. Two-dimensional multivoxel 1H magnetic resonance spectroscopy scans were performed before and after stimulation. The ratios of N-acetylaspartate (NAA), glutamate/glutamine (Glx), and gamma -amino butyric acid (GABA) to creatine (Cr) were determined and compared between the two groups. The distribution of metabolites between the left and right auditory cortex was also determined. Before stimulation, left and right side NAA/Cr and right side GABA/Cr were significantly lower, whereas right side Glx/Cr was significantly higher in the older group compared with the young group. After stimulation, left and right side NAA/Cr and GABA/Cr were significantly lower, whereas left side Glx/Cr was significantly higher in the older group compared with the young group. There was obvious asymmetry in right side Glx/Cr and left side GABA/Cr after stimulation in young group, but not in older group. In summary, there is marked hemispheric asymmetry in auditory cortical metabolites following pure tone stimulation in young, but not older adults. This reduced asymmetry in older adults may at least in part underlie the speech perception difficulties/presbycusis experienced by aging adults. PMID- 24222866 TI - Clinical management of suppurative osteomyelitis, bisphosphonate-related osteonecrosis, and osteoradionecrosis: report of three cases and review of the literature. AB - In the past, osteomyelitis was frequent and characterized by a prolonged course, treatment response uncertainty, and occasional disfigurement. Today, the disease is less common; it is believed that the decline in prevalence may be attributed to increased availability of antibiotics and improvement of overall health patterns. Currently, more common osteomyelitis variants are seen, namely, osteoradionecrosis (ORN) and bisphosphonate-related osteonecrosis of the jaws (BRONJ). Osteomyelitis, ORN, and BRONJ can present with similar symptoms, signs, and radiographic findings. However, each condition is a separate entity, with different treatment approaches. Thus, accurate diagnosis is essential for adequate management and improved patient prognosis. The aim of this paper is to report three cases of inflammatory lesions of the jaws-osteomyelitis, ORN, and BRONJ-and to discuss their etiology, clinical aspects, radiographic findings, histopathological features, treatment options, and preventive measures. PMID- 24222867 TI - Multiple dental and skeletal abnormalities in an individual with filippi syndrome. AB - Filippi syndrome is an autosomal recessive condition characterized by variable soft tissue syndactyly of the fingers and toes, microcephaly, pre- and postnatal growth retardation, mildly abnormal craniofacial appearance, and mental retardation. We report on a child with Filippi syndrome who shows syndactyly of fingers, severe postnatal growth retardation, postnatal microcephaly, and moderate to severe mental retardation. In addition, there is a mildly dysmorphic face along with ocular and a number of dental abnormalities. Radiologically, hands demonstrate bony syndactyly, without any hypoplasia of bones. This phenotype can easily be classified in the group of craniodigital syndromes, but it is difficult to make a more clearly defined diagnosis, based on other minor anomalies, because of the presence of overlapping features. On the basis of various pathognomic features, we conclude that our patient could be an additional case of Filippi syndrome. Moreover, newly recognised features in this patient may be due to variability in phenotypic expression. PMID- 24222865 TI - Neurobiology of major depressive disorder. AB - We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed. PMID- 24222868 TI - Microabrasion: an effective method for improvement of esthetics in dentistry. AB - Enamel microabrasion can eliminate enamel irregularities and discoloration defects, thus improving the appearance of teeth. This paper presents the latest treatment protocol of enamel microabrasion to remove stains on the enamel surface. It has been verified that teeth submitted to microabrasion acquire a yellowish colour because of the thinness of the remaining enamel, revealing the colour of dentinal tissue to a greater degree. Enamel microabrasion is a technique that can be used to correct discoloured enamel. Enamel microabrasion was developed in the mid-1980s as a method of eliminating enamel discolouration defects and improving the appearance of teeth. Several years after the method was developed, much has been learned about this technique, long-term results of treatment, and microscopic changes to the enamel surface that have distinguishable clinical implications. In addition, certain patients can benefit from enamel microabrasion to yield attractive cosmetic results. The aim of this study was to report the clinical case of a male patient of 25 years with moderate fluorosis, whose smile was re-established by the use of an enamel microabrasion technique, with 18% hydrochloric acid and pumice slurry shown to be a safe and efficient method for removing fluorosis stains. PMID- 24222869 TI - Unusual clinical presentation of cutaneous angiosarcoma masquerading as eczema: a case report and review of the literature. AB - An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve. At our clinic, excisional biopsy of the forehead lesion and scouting biopsies from the contralateral cheek were performed which revealed cutaneous angiosarcoma. The described case illustrates that dermatitis-like features should be considered as a rare clinical manifestation of cutaneous angiosarcoma. It also demonstrates that these lesions may respond well to radiotherapy as a single modality. PMID- 24222870 TI - Cutaneous leishmaniasis of the eyelid: a case report. AB - Cutaneous leishmaniasis is endemic in certain areas of Iran, and in recent years, there has been an increase in the number of reports for rare and new forms of cutaneous leishmaniasis. We describe one unusual clinical form of cutaneous leishmaniasis. In a 27-year-old man, who noted a pimple on the upper eyelid 4 months before. The lesion was nodular and measured 1 cm * 1 cm in diameter. A diagnosis of eyelid cutaneous leishmaniasis was made, and treatment was started with intramuscular meglumine antimonate. He showed a dramatic response, and the lesion almost completely disappeared. PMID- 24222871 TI - De novo glioblastoma in the territory of a prior middle cerebral artery infarct. AB - We report a case of a patient who developed glioblastoma in the territory of a previous infarction. Two years after an ischemic stroke, the patient presented with a cystic, necrotic, and heterogeneously enhancing mass. Open biopsy and debulking of the mass with histological analysis revealed the mass to be glioblastoma. Though several cases of posttraumatic GBM have been reported, this is the first proposed case of GBM after an ischemic stroke. From this case, we suggest that the ischemic stroke, like other forms of cortical injury, may predispose to glioblastoma formation. PMID- 24222872 TI - An interesting case of barbiturate automatism and review of literature. AB - A 48 year old man with a diagnosis of HIV infection since 1993, on highly active anti-retro viral therapy (HAART) with stable CD4 count and undetectable viral load for years and seizure disorder presented with recurrent drowsiness. His seizures were well controlled on phenobarbitone for years. Repeated laboratory evaluation demonstrated toxic levels of phenobarbitone in his blood. A thorough clinical, psychiatric, laboratory and imaging evaluation did not reveal any obvious etiology for the recurrent barbiturate intoxication in this man. Our findings suggest the possible diagnosis of barbiturate drug automatism in this patient. Though drug automatism is a controversial entity, it merits continued attention. There are recent reports of similar phenomenon with newer sedative agents such as Zolpidem. It is important to be aware of this phenomenon as a possible explanation for recurrent intoxication with barbiturates without a clear etiology for drug overdose. PMID- 24222873 TI - Primary ovarian large B-cell lymphoma. AB - The involvement of the ovary by malignant lymphoma is a well-known late manifestation of disseminated nodal disease. Primary ovarian lymphoma is rare. We herein describe a case of primary ovarian diffuse large B-cell lymphoma involving unilateral ovary in a 38-year-old woman which was detected incidentally. Preoperative ultrasonic imaging showed a 46*42 mm heterogeneous cystic mass. Laparotomy revealed that left adnexal mass and left salpingo-oophorectomy was performed. The current diagnosis was determined after immunostaining. The patient was treated with R-CHOP regimen after the operation. She remains cancer-free 24 months after chemotherapy. PMID- 24222874 TI - Vulvar fibroadenoma with lactational changes in ectopic breast tissue. AB - Ectopic breast tissue represents any type of breast tissue found outside its normal location in the pectoral region. The second most common location for ectopic breast tissue after axilla is the vulvar region. We present a case of a healthy 20-year-old female, G1P1, who presented to the Emergency Department with a sudden increase in size of a painful mass located in her vulva, which started 4 days after a spontaneous vaginal delivery and 3 days after initiation of breast feeding of her newborn. She reported a stable, smaller, painless mass in the same location for almost 2 years prior to this episode. After surgical excision, a fibroadenoma with lactation changes within ectopic breast tissue was confirmed. PMID- 24222875 TI - Clinical and radiologic signs of relapsed ovarian germ cell tumor: tissue is the issue. AB - Malignant ovarian germ cell tumor is a rare disease, but with current treatment strategies including surgery and platinum based chemotherapy survival is excellent. After treatment, intensive followup is indicated to encounter tumor relapse at an early stage. This case describes a 22-year-old female with a history of common variable immune deficiency (CVID) who underwent a resection of a large ovarian germ cell tumor followed by 4 cycles of cisplatin and etoposide resulting in clinical complete remission. During followup, she developed a mass at the umbilicus and ascites. Initially, the cytology of the ascites was interpreted as tumor positive, suspicious of relapse of the disease, but tumor markers remained negative. However, during laparoscopy it turned out to be a mature teratoma, which can develop after chemotherapy, the so called growing teratoma syndrome. In retrospect, the ascites was false positive. This case shows that current diagnostic tools are not sufficient to distinguish between vital tumor and mature teratoma and can be misleading. Tumor biopsy and/or laparoscopic inspection are therefore indicated. PMID- 24222876 TI - Renal medullary cancer in a patient with sickle cell trait. AB - Renal medullary cancer is a rare malignancy almost exclusively seen in young patients of African ethnicity. These patients often present with the cardinal symptoms of hematuria, flank pain, and an abdominal mass, and this malignancy has been associated with patients carrying sickle cell trait. It is estimated that 300 million people worldwide carry sickle cell trait, and the presence of hematuria in these patients should be treated as a harbinger of a possible malignancy. Notably, this tumor mostly develops on the right side of the body. Patients often present with it at an advanced stage and the prognosis is poor. Therefore, a high index of suspicion in a patient of African descent presenting with a right sided abdominal mass and hematuria may assist in an early diagnosis. Current chemotherapy options are very limited, and early detection may provide a chance for surgical resection. It may also provide a bigger time frame for the initiation of novel chemotherapy regimens in patients who fail current chemotherapy regimens. PMID- 24222877 TI - Malignant mesothelioma after household exposure to asbestos. AB - Malignant mesothelioma (MM) is an aggressive cancer that has been closely linked to asbestos exposure. Initially recognized as an occupational cancer in male workers, MM was later found to occur in their family members as well. We report the case of an 89-year-old female who presented with abdominal distention, pain, and findings consistent with malignant ascites. Family history was significant for fatal mesothelioma in her husband of 40 years, who was a worker at a tile factory. The diagnosis of MM was confirmed on pathologic examination of the omental core biopsy. PMID- 24222878 TI - Simultaneous periprosthetic acetabular fracture and contralateral B-type compression injury of the pelvic ring: a case report of a rare injury combination. AB - The periprosthetic fracture of the acetabulum is a rare injury, and its management is only sporadically reported in the literature. A few case reports are available which mainly focus on periprosthetic acetabular fractures in the elderly population. In our case, a 32-year-old patient suffered from a periprosthetic acetabular fracture in combination with a pelvic ring injury following a high velocity accident. The fracture morphology allowed a salvage of the prosthesis with an open reduction and internal fixation with a good radiographic and functional outcome one year after trauma. PMID- 24222879 TI - Endoscopic drainage of an odontogenic pterygoid muscle abscess. AB - The infratemporal fossa (ITF) is a potential space bounded by bony structures that can be occupied by both benign and malignant tumors. It is also a potential area of abscess development, most commonly of dental origin. As with any abscess, the treatment of an ITF abscess is surgical drainage. We present a case of an ITF abscess involving the pterygoid muscles following dental extraction in a poorly controlled diabetic patient. The ITF was accessed with an endoscopic transseptal approach through the maxillary sinus to drain the abscess. This case of successful management supports the feasibility of the endoscopic approach in dealing with abscesses of the ITF. PMID- 24222880 TI - Triple-divided concha bullosa: a new anatomic variation. AB - In recent years, with the widespread use of imaging techniques such as paranasal sinus computed tomography (CT), many variations of nasal turbinates have been described. One of these variations known as concha bullosa (CB) is pneumatization of nasal turbinates. CB is the most frequently encountered anatomical variations of the middle turbinate. The term of septated concha bullosa has been described recently and it is an uncommon pneumatization anomaly of the middle turbinate. There has not been any study that correlates the number of septations and the presence of sinonasal pathologies. We hereby present a case of triple septated concha bullosa that has not been reported so far. PMID- 24222881 TI - Off-label use of liraglutide in the management of a pediatric patient with type 2 diabetes mellitus. AB - Liraglutide is a glucagon-like peptide 1 (GLP-1) analog indicated for the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise in adults. Liraglutide lowers blood glucose levels by stimulating insulin secretion and decreasing glucagon release in glucose-dependent manners, increases satiety, and delays gastric emptying. Liraglutide, unlike metformin and insulin, is not approved for use in the pediatric population. We report the successful off-label use of liraglutide in an obese, 16 year old Caucasian female with type 2 diabetes mellitus. PMID- 24222882 TI - Mirtazapine treatment of a severe depressive episode and resolution of elevated inflammatory markers. AB - Depression has been shown to be associated with systemic inflammatory activity and the mode of action of several antidepressants appears to involve immunomodulation. Effects on immune system activity have also recently been observed in correlation with therapeutic response to mirtazapine in cardiac patients with depression, but no study has yet examined these effects in otherwise physically healthy depressed patients treated with mirtazapine. This report describes an association between a clinical antidepressant response and a decrease in markers of systemic inflammation observed during pharmacotherapy with mirtazapine in a severely depressed but physically well patient. This observation adds to the evidence that changes in inflammatory responses may be implicated in the mode of action of antidepressants. Further studies of antidepressant responses to mirtazapine and levels of inflammatory markers in depressed patients without medical comorbidity can help elucidate the role of the immune system in the pathophysiology of depression, and hence contribute to the development of novel antidepressant therapies. PMID- 24222883 TI - Acute Dilatation, Ischemia, and Necrosis of Stomach without Perforation. AB - Acute gastric dilatation can have multiple etiologies which may lead to ischemia of the stomach. Without proper timely diagnosis and treatment, potentially fatal events such as gastric perforation, haemorrhage, and other serious complications can occur. Here we present a 36-year-old man who came to the casualty with pain abdomen and distension for 2 days. Clinically, abdomen was asymmetrically distended more in the left hypochondrium and epigastrium region. Straight X-ray abdomen showed opacified left hypochondrium with nonspecific gaseous distension of bowel. Exploratory laparotomy revealed dilated stomach with patchy gangrene over lesser curvature and fundic area. About 4 litres of brownish fluid along with semisolid undigested food particles was sucked out (mainly undigested pieces of meat). Limited resection of gangrenous areas and primary repair were done along with feeding jejunostomy. Necrosis of the stomach was confirmed on histopathology. The patient recovered well and was discharged on the tenth postoperative day. PMID- 24222884 TI - Effect of ivabradine on endothelial function in diastolic and right heart failure patients. AB - Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 +/- 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 +/- 2.2 versus 24.3 +/- 3.2 (P = 0.05) in basal recording and 30.4 +/- 2.1 versus 23.3 +/- 2.9 (P = 0.002), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients. PMID- 24222885 TI - Preferential selectivity of inhibitors with human tau protein kinase gsk3beta elucidates their potential roles for off-target Alzheimer's therapy. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta peptides (Abeta) and neurofibrillary tangles (NFTs). The abnormal phosphorylation of tau leads to the formation of NFTs produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia. Hence, tau kinases have become potential drug target candidates for small molecule inhibitors. With an aim to explore the identification of a common inhibitor, this investigation was undertaken towards analyzing all 10 tau kinases which are implicated in phosphorylation of AD. A set of 7 inhibitors with varied scaffolds were collected from the Protein Data Bank (PDB). The analysis, involving multiple sequence alignment, 3D structural alignment, catalytic active site overlap, and docking studies, has enabled elucidation of the pharmacophoric patterns for the class of 7 inhibitors. Our results divulge that tau protein kinases share a specific set of conserved structural elements for the binding of inhibitors and ATP, respectively. The scaffold of 3-aminopyrrolidine (inhibitor 6) exhibits high preferential affinity with GSK3beta. Surprisingly, the PDB does not contain the structural details of GSK3beta with this specific inhibitor. Thus, our investigations provide vital clues towards design of novel off-target drugs for Alzheimer's. PMID- 24222886 TI - Undersampling taxa will underestimate molecular divergence dates: an example from the South american lizard clade liolaemini. AB - Methods for estimating divergence times from molecular data have improved dramatically over the past decade, yet there are few studies examining alternative taxon sampling effects on node age estimates. Here, I investigate the effect of undersampling species diversity on node ages of the South American lizard clade Liolaemini using several alternative subsampling strategies for both time calibrations and taxa numbers. Penalized likelihood (PL) and Bayesian molecular dating analyses were conducted on a densely sampled (202 taxa) mtDNA based phylogenetic hypothesis of Iguanidae, including 92 Liolaemini species. Using all calibrations and penalized likelihood, clades with very low taxon sampling had node age estimates younger than clades with more complete taxon sampling. The effect of Bayesian and PL methods differed when either one or two calibrations only were used with dense taxon sampling. Bayesian node ages were always older when fewer calibrations were used, whereas PL node ages were always younger. This work reinforces two important points: (1) whenever possible, authors should strongly consider adding as many taxa as possible, including numerous outgroups, prior to node age estimation to avoid considerable node age underestimation and (2) using more, critically assessed, and accurate fossil calibrations should yield improved divergence time estimates. PMID- 24222887 TI - Circulating anti-beta2-glycoprotein I antibodies are associated with endothelial dysfunction, inflammation, and high nitrite plasma levels in patients with intermittent claudication. AB - Our aim is to investigate a possible association of circulating anti-beta2 glycoprotein I antibodies (ABGPI) with the endothelial dysfunction, nitric oxide bioactivity dysregulation, and the inflammatory status that surrounds peripheral arterial disease. We carried out an observational translational study, including 50 male patients with intermittent claudication and a healthy control group of 10 male subjects, age and sex matched with the cases. Flow-mediated arterial dilatation (FMAD) was assessed as a surrogate of endothelial dysfunction, and C reactive protein (hsCRP) was determined as a marker of inflammation. Nitrite plasma levels were measured by colorimetric analysis. Circulating ABGPI titer was detected with indirect immunofluorescence. Titers <1 : 10 represented the reference range and the lower detection limit of the test. Circulating ABGPI titer >=1 : 10 was detected in 21 (42%) patients and in none of the control subjects (P < 0.01). Patients with ABGPI titer >=1 : 10 had a lower FMAD (P = 0.01). The CRP levels were higher in patients with ABGPI titer >=1 : 10 (P = 0.04). The nitrite plasma levels were higher in patients with ABGPI titer >=1 : 10 (P < 0.01). These data suggest that these circulating ABGPI may collaborate in the development of atherosclerosis; however, further prospective studies are required to establish a causal relationship. PMID- 24222888 TI - Relationship between Weight, Body Mass Index, and Bone Mineral Density in Men Referred for Dual-Energy X-Ray Absorptiometry Scan in Isfahan, Iran. AB - Objective. Although several studies have investigated the association between body mass index (BMI) and bone mineral density (BMD), the results are inconsistent. The aim of this study was to further investigate the relation between BMI, weight and BMD in an Iranian men population. Methods. A total of 230 men 50-79 years old were examined. All men underwent a standard BMD scans of hip (total hip, femoral neck, trochanter, and femoral shaft) and lumbar vertebrae (L2 L4) using a Dual-Energy X-ray Absorptiometry (DXA) scan and examination of body size. Participants were categorised in two BMI group: normal weight <25.0 kg/m(2) and overweight and obese, BMI >= 25 kg/m(2). Results. Compared to men with BMI >= 25, the age-adjusted odds ratio of osteopenia was 2.2 (95% CI 0.85, 5.93) and for osteoporosis was 4.4 (1.51, 12.87) for men with BMI < 25. It was noted that BMI and weight was associated with a high BMD, compatible with a diagnosis of osteoporosis. Conclusions. These data indicate that both BMI and weight are associated with BMD of hip and vertebrae and overweight and obesity decreased the risk for osteoporosis. The results of this study highlight the need for osteoporosis prevention strategies in elderly men as well as postmenopausal women. PMID- 24222889 TI - Determination of morphine and codeine in human urine by gas chromatography-mass spectrometry. AB - A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the determination of morphine and codeine in human urine. The GC-MS conditions were developed. The analysis was carried out on a HP 1MS column (30 m * 0.25 mm, 0.25 MU m) with temperature programming, and Helium was used as the carrier gas with a flow rate of 1.0 mL/min. Selected ion monitoring (SIM) mode was used to quantify morphine and codeine. The derivation solvent, temperature, and time were optimized. A mixed solvent of propionic anhydride and pyridine (5 : 2) was finally used for the derivation at 80 degrees C for 3 min. Linear calibration curves were obtained in the concentration range of 25-2000.0 ng/mL, with a lower limit of quantification of 25 ng/mL. The intra- and interday precision (RSD) values were below 13%, and the accuracy was in the range 87.2-108.5%. This developed method was successfully used for the determination of morphine and codeine in human urine for forensic identification study. PMID- 24222890 TI - Knowledge, Attitude, and Practice of Voluntary Blood Donation among Healthcare Workers at the University of Benin Teaching Hospital, Benin City, Nigeria. AB - Introduction. Adequate and safe blood supply has remained a challenge in developing countries like ours. There is a high dependency on family replacement and remunerated blood donors in our environment which carries an attendant increased risk of transfusion transmissible infection. Objectives. The objectives of this study were to assess the knowledge, attitude, and practice of voluntary blood donation among healthcare workers (nonphysicians) and to identify and recruit potential voluntary blood donors. Methodology. This was a cross-sectional descriptive study carried out at the University of Benin Teaching Hospital, Benin City. A total of 163 staffs were recruited. Pretest questionnaires were used to assess their knowledge, attitude, and practice of voluntary blood donation. Statistical Analysis. The responses were collated and analyzed with the Statistical Package for Social Sciences (SPSS) 16. The association between blood donation practice and gender of respondents, category of staff, and level of education was tested using Chi-square and Fisher's tests where appropriate. P < 0.05 were considered statistically significant. Results. The median age of the respondents was 32 years (18-56) with females accounting for 55.6% (90). A total of 74.8% (122) attained tertiary education, and 55.8% (91) of respondents were senior staffs. The majority has good knowledge and positive attitude towards donation; however, only 22.1% (36) have donated blood with 41.7% (15) of these being voluntary. Male workers were more likely to donate (P < 0.05). There is no significant association between blood donation and level of education. Conclusion. There is a strong disparity between the knowledge, attitude, and practice of voluntary donation amongst healthcare workers. PMID- 24222891 TI - Optimization of Ex Vivo Expansion of Limbal Epithelial Progenitors by Maintaining Native Niche Cells on Denuded Amniotic Membrane. AB - PURPOSE: Transplantation of ex vivo expanded limbal epithelial progenitor cells (LEPCs) on epithelially denuded amniotic membrane (dAM) in supplemented hormonal epithelial medium (SHEM) is an alternative solution for treating corneal blindness due to limbal stem cell (SC) deficiency. Because the phenotype of limbal niche cells (NCs) is preserved better in serum-free modified embryonic stem cell (ESC) medium (MESCM) than SHEM, we question whether the aforementioned expansion protocol can be further optimized by maintaining limbal NCs using MESCM. METHODS: Collagenase-isolated limbal clusters were cultured on dAM in SHEM or MESCM for 8 to 10 days. Epithelial outgrowth sheets removed by dispase were subjected to real-time quantitative polymerase chain reaction (qPCR) and immunostaining for expression of corneal epithelial markers (p63alpha, pax6, and K12) and NC markers (FLK-1, CD34, CD31, PDGFR-B, and alpha-SMA). A total of 1000 single cells were seeded on 6-well dish containing 3T3 feeder layers for 12 to 14 days before rhodamine B staining. RESULTS: Epithelial outgrowth in SHEM showed a significant loss of corneal SC and ESC markers when compared with freshly collagenase-isolated limbal clusters. Although the epithelial outgrowth was slower in MESCM, epithelial cell size was consistently smaller than that found in SHEM. Furthermore, MESCM maintained a significantly higher percentage of PCK-/ Vim+ cells and exhibited a significant upregulation of NC markers and corneal epithelial SC markers (K15, Bmi-1, and Msi-1) than SHEM. Furthermore, the number of purported holoclones was significantly promoted in MESCM than SHEM. CONCLUSION: These data collectively suggest that MESCM can be used to replace SHEM to further promote expansion of LEPC by maintaining limbal native NCs. TRANSLATIONAL RELEVANCE: Effective ex vivo expansion of limbal epithelial SC is a first and important step toward the success of treating corneal blindness caused by limbal stem cell deficiency and paves the way for future applications in regenerative medicine. PMID- 24222892 TI - Comparative inference of duplicated genes produced by polyploidization in soybean genome. AB - Soybean (Glycine max) is one of the most important crop plants for providing protein and oil. It is important to investigate soybean genome for its economic and scientific value. Polyploidy is a widespread and recursive phenomenon during plant evolution, and it could generate massive duplicated genes which is an important resource for genetic innovation. Improved sequence alignment criteria and statistical analysis are used to identify and characterize duplicated genes produced by polyploidization in soybean. Based on the collinearity method, duplicated genes by whole genome duplication account for 70.3% in soybean. From the statistical analysis of the molecular distances between duplicated genes, our study indicates that the whole genome duplication event occurred more than once in the genome evolution of soybean, which is often distributed near the ends of chromosomes. PMID- 24222893 TI - Integrated analysis of long noncoding RNA and coding RNA expression in esophageal squamous cell carcinoma. AB - Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the "cancer initiatome." Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer. PMID- 24222894 TI - Pharmacological evaluation and antifertility activity of Jatropha gossypifolia in rats. AB - OBJECTIVES: Pharmacological and antifertility activity evaluation of Jatropha gossypifolia in rats. METHODS: The antifertility activity of the extracts of Jatropha gossypifolia in rats was evaluated using two experimental animal models. Estrogenic activity was evaluated in immature female rats using ethinyl estradiol as standard. Anti-implantation and early abortifacient activity was performed in female Wistar rats by determining the number of implantations and implantation resorptions. RESULTS: In estrogenic activity evaluations, the ethanolic and aqueous extracts offered significant estrogen-like activity at 400 mg kg-1 p.o. by increasing the uterine weight compared to vehicle control group. Ethanolic extract (400 mg kg-1, p.o.) treatment significantly decreased the number of implants and increased the number of resorptions compared to vehicle control group. CONCLUSION: The results of the present study provide the evidence of the anti-fertility activity of Jatropha gossypifolia as claimed in the traditional use. The results are consistent with the literature reports related to the antifertility effect of flower extracts of Jatropha gossypifolia. PMID- 24222895 TI - Enzyme reaction annotation using cloud techniques. AB - An understanding of the activities of enzymes could help to elucidate the metabolic pathways of thousands of chemical reactions that are catalyzed by enzymes in living systems. Sophisticated applications such as drug design and metabolic reconstruction could be developed using accurate enzyme reaction annotation. Because accurate enzyme reaction annotation methods create potential for enhanced production capacity in these applications, they have received greater attention in the global market. We propose the enzyme reaction prediction (ERP) method as a novel tool to deduce enzyme reactions from domain architecture. We used several frequency relationships between architectures and reactions to enhance the annotation rates for single and multiple catalyzed reactions. The deluge of information which arose from high-throughput techniques in the postgenomic era has improved our understanding of biological data, although it presents obstacles in the data-processing stage. The high computational capacity provided by cloud computing has resulted in an exponential growth in the volume of incoming data. Cloud services also relieve the requirement for large-scale memory space required by this approach to analyze enzyme kinetic data. Our tool is designed as a single execution file; thus, it could be applied to any cloud platform in which multiple queries are supported. PMID- 24222896 TI - Differences in muscle activation patterns during sit to stand task among subjects with and without intellectual disability. AB - The aim of this study is to analyse the differences in muscle activity between subjects who have intellectual disability and healthy subjects when they make the transition from sitting to standing positions. A cross-sectional study. A group of adults was divided into two subgroups: with and without intellectual disability (ID). The means of the basic features in both groups were 22.13 and 22.83 for age, 66.38 and 67.67 for weight, and 173.38 and 174.33 for height, for the ID (n = 8) and without ID (n = 7) groups, respectively. Each subject performed three sets of five repetitions during which, starting from sitting, they had to get up and sit on the chair. The recording of muscle activity was performed using surface electromyography taking the measures of muscle activity of different muscles of the lower limbs. The results showed differences in the pattern of muscle activity between groups during sitting to standing movement. PMID- 24222897 TI - Reconstruction and analysis of human kidney-specific metabolic network based on omics data. AB - With the advent of the high-throughput data production, recent studies of tissue specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID- 24222898 TI - Evaluation of sample stability and automated DNA extraction for fetal sex determination using cell-free fetal DNA in maternal plasma. AB - OBJECTIVE: The detection of paternally inherited sequences in maternal plasma, such as the SRY gene for fetal sexing or RHD for fetal blood group genotyping, is becoming part of daily routine in diagnostic laboratories. Due to the low percentage of fetal DNA, it is crucial to ensure sample stability and the efficiency of DNA extraction. We evaluated blood stability at 4 degrees C for at least 24 hours and automated DNA extraction, for fetal sex determination in maternal plasma. METHODS: A total of 158 blood samples were collected, using EDTA K tubes, from women in their 1st trimester of pregnancy. Samples were kept at 4 degrees C for at least 24 hours before processing. An automated DNA extraction was evaluated, and its efficiency was compared with a standard manual procedure. The SRY marker was used to quantify cfDNA by real-time PCR. RESULTS: Although lower cfDNA amounts were obtained by automated DNA extraction (mean 107,35 GE/mL versus 259,43 GE/mL), the SRY sequence was successfully detected in all 108 samples from pregnancies with male fetuses. CONCLUSION: We successfully evaluated the suitability of standard blood tubes for the collection of maternal blood and assessed samples to be suitable for analysis at least 24 hours later. This would allow shipping to a central reference laboratory almost from anywhere in Europe. PMID- 24222899 TI - A numerical study to compare stimulations by intraoperative microelectrodes and chronic macroelectrodes in the DBS technique. AB - Deep brain stimulation is a clinical technique for the treatment of parkinson's disease based on the electric stimulation, through an implanted electrode, of specific basal ganglia in the brain. To identify the correct target of stimulation and to choose the optimal parameters for the stimulating signal, intraoperative microelectrodes are generally used. However, when they are replaced with the chronic macroelectrode, the effect of the stimulation is often very different. Here, we used numerical simulations to predict the stimulation of neuronal fibers induced by microelectrodes and macroelectrodes placed in different positions with respect to each other. Results indicate that comparable stimulations can be obtained if the chronic macroelectrode is correctly positioned with the same electric center of the intraoperative microelectrode. Otherwise, some groups of fibers may experience a completely different electric stimulation. PMID- 24222900 TI - Content of trans fatty acids in human cheek epithelium: comparison with serum and adipose tissue. AB - Studies pertaining to trans fatty acids (TFA), which have been implicated in development of chronic diseases, are more relevant in developing countries where nutrition transition is changing traditional habits and practices. Measuring TFA is an arduous task because of the need for fat biopsies. This study identifies a tissue, which can be easily accessed for analytical measurement of trans fatty acid. In this cross-sectional study, fatty acid in adipose tissue, cheek epithelium, and blood samples were assessed by gas chromatography. Spearman correlation coefficient was computed to study the correlation of fatty acid distribution among the three tissues. The correlation coefficient of total trans fatty acid between cheek epithelium and serum was 0.30 (P < 0.02) and between cheek epithelium and adipose tissue was 0.33 (P < 0.019). This study is the first to report trans fatty acid profile in cheek epithelium giving scope for utilizing the cheek epithelium as a tissue for objective assessment of trans fatty acid intake. PMID- 24222901 TI - Depigmented allergoids reveal new epitopes with capacity to induce IgG blocking antibodies. AB - BACKGROUND: The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. METHODS: Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. RESULTS: Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. CONCLUSIONS: Depigmented polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT. PMID- 24222902 TI - Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis. AB - BACKGROUND: Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. METHODS: We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I2 statistic. RESULTS: Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08-0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25-0.86) and renal impairment (OR 0.34 95%, CI 0.15-0.75) when albumin was used. CONCLUSION: The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis. PMID- 24222903 TI - Mycobacterium tuberculosis infection following kidney transplantation. AB - INTRODUCTION AND AIMS: Post-transplant tuberculosis (TB) is a problem in successful long-term outcome of renal transplantation recipients. Our objective was to describe the pattern and risk factors of TB infection and the prognosis in our transplant recipients. PATIENTS AND METHODS: This study was a retrospective review of the records of 491 renal transplant recipients in our hospital during the period from January 1986 to December 2009. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed. RESULTS: 16 patients (3,2%) developed post-transplant TB with a mean age of 32,5 +/- 12,7 (range: 13-60) years and a mean post-transplant period of 36,6 months (range: 12,3 months-15,9 years). The forms of the diseases were pulmonary in 10/16 (62,6%), disseminated in 3/16 (18,7%), and extrapulmonary in 3/16 (18,7%). Graft dysfunction was observed in 7 cases (43,7%) with tissue-proof acute rejection in 3 cases and loss of the graft in 4 cases. Hepatotoxicity developed in 3 patients (18,7%) during treatment. Recurrences were observed in 4 cases after early stop of treatment. Two patients (12.5%) died. CONCLUSION: Extra pulmonary and disseminated tuberculosis were observed in third of our patients. More than 9 months of treatment may be necessary to prevent recurrence. PMID- 24222904 TI - Repeatability and reproducibility of measurements using a NT-530P noncontact tono/pachymeter and correlation of central corneal thickness with intraocular pressure. AB - PURPOSE: To investigate the repeatability and reproducibility of intraocular pressure (IOP) and central corneal thickness (CCT) measurements using a noncontact tono/pachymeter (NT-530P) and to assess the correlation of CCT with IOP. METHODS: Forty-six eyes of healthy volunteers were measured by two examiners. Three consecutive measurements per eye were performed. Repeatability was assessed using the coefficient of variation, and reproducibility was assessed using Bland-Altman plots. Linear correlations were used to determine agreement between CCT and noncorrected IOP and CCT and corrected IOP, which was calculated using a formula built into the NT-530P. RESULTS: The coefficient of variation for IOP was 6.4% and for CCT was 0.4%. The 95% limits of agreement between examiners were -0.17 +/- 1.42 mmHg (range: -2.95 to 2.61 mmHg) for IOP, -0.93 +/- 4.37 MU m (range: -9.50 to 7.64 MUm) for CCT. The corrected IOP was significantly higher than the noncorrected IOP (P = 0.010.3). The noncorrected IOP significantly correlated with CCT (r = -0.4883, P = 0.0006). The corrected IOP showed no significant correlation with CCT (r = -0.0285, P = 0.8509). CONCLUSIONS: NT-530P offered repeatability and reproducibility in both IOP and CCT measurements. The corrected IOP calculated using the NT-530P was independent of the CCT, suggesting that this IOP may be less influenced by the central corneal thickness. PMID- 24222905 TI - A comparison between tube surgery, ND:YAG laser and diode laser cyclophotocoagulation in the management of refractory glaucoma. AB - PURPOSE: To compare the results of intraocular pressure (IOP) reduction by 3 treatment modalities, (a) glaucoma tube implants, (b) noncontact YAG laser cyclophotocoagulation (cycloYAG), and (c) contact transscleral diode laser cyclophotocoagulation (cyclodiode), in cases of advanced glaucoma refractory to alternative treatments. METHODS: A consecutive group of 45 eyes that received cycloYAG were matched against two control groups of patients who had received tube surgery or cyclodiode, each control group having been derived from a database of patients. RESULTS: Mean pretreatment IOP improved from 41.3, 38.6, and 32.0 mmHg for the tube, cycloYAG, and cyclodiode groups, respectively, to 16.4, 22.1, and 19.3 mmHg, respectively. Treatment success was achieved in 78%, 69%, and 71% of the tube, cycloYAG, and cyclodiode groups, respectively. Visual acuity deteriorated 2 or more Snellen lines in 16%, 7%, and 9% of the patients in the tube, cycloYAG, and cyclodiode groups, respectively. Complications included retinal detachment, hypotony, and phthisis. CONCLUSIONS: All 3 methods provided acceptable IOP lowering in the short and medium term. Control of IOP was best in patients receiving tube surgery. Cyclodiode and cycloYAG treatments were similarly effective in lowering IOP. Tube surgery was associated with a greater incidence of sight threatening complications. PMID- 24222906 TI - Fibrinogen-induced streptococcus mutans biofilm formation and adherence to endothelial cells. AB - Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis. PMID- 24222907 TI - Evaluation of wall correction factor of INER's air-kerma primary standard chamber and dose variation by source displacement for HDR 192Ir brachytherapy. AB - The aim of the present study was to estimate the wall effect of the self-made spherical graphite-walled cavity chamber with the Monte Carlo method for establishing the air-kerma primary standard of high-dose-rate (HDR) 192Ir brachytherapy sources at the Institute of Nuclear Energy Research (INER, Taiwan). The Monte Carlo method established in this paper was also employed to respectively simulate wall correction factors of the 192Ir air-kerma standard chambers used at the National Institute of Standards and Technology (NIST, USA) and the National Physical Laboratory (NPL, UK) for comparisons and verification. The chamber wall correction calculation results will be incorporated into INER's HDR 192Ir primary standard in the future. For the brachytherapy treatment in the esophagus or in the bronchi, the position of the isotope may have displacement in the cavity. Thus the delivered dose would differ from the prescribed dose in the treatment plan. We also tried assessing dose distribution due to the position displacement of HDR 192Ir brachytherapy source in a phantom with a central cavity by the Monte Carlo method. The calculated results could offer a clinical reference for the brachytherapy within the human organs with cavity. PMID- 24222908 TI - Comparison of stress-hemoconcentration correction techniques for stress-induced coagulation. AB - When examining stress effects on coagulation, arithmetic correction is typically used to adjust for concomitant hemoconcentration but may be inappropriate for coagulation activity assays. We examined a new physiologically relevant method of correcting for stress-hemoconcentration. Blood was drawn from healthy men (N = 40) during baseline, mental stress, and recovery, and factor VII activity (FVII:C), factor VIII activity (FVIII:C), activated partial thromboplastin time (APTT), prothrombin time (PT%), fibrinogen, D-dimer, and plasma volume were determined. Three hemoconcentration correction techniques were assessed: arithmetic correction and two reconstitution techniques using baseline plasma or physiological saline. Area-under-the-curve (AUC) was computed for each technique. For FVII:C, uncorrected AUC was significantly greater than AUC corrected arithmetically. For PT%, uncorrected AUC was significantly greater than AUC corrected with saline or arithmetically. For APTT, uncorrected AUC was significantly less than AUC corrected with saline and greater than AUC corrected arithmetically. For fibrinogen, uncorrected AUC was significantly greater than AUC corrected with saline or arithmetically. For D-dimer, uncorrected AUC was significantly greater than AUC corrected arithmetically. No differences in AUC were observed for FVIII:C. Saline reconstitution seems most appropriate when adjusting for hemoconcentration effects on clotting time and activity. Stress hemoconcentration accounted for the majority of coagulation changes. PMID- 24222909 TI - Ovarian and breast cancer spheres are similar in transcriptomic features and sensitive to fenretinide. AB - Cancer stem cells (CSCs) are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future. PMID- 24222910 TI - Sensitivity of rabbit ventricular action potential and Ca2+ dynamics to small variations in membrane currents and ion diffusion coefficients. AB - Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%-10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl- background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl- channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID- 24222911 TI - Molecular imaging in traditional Chinese medicine therapy for neurological diseases. AB - With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM. PMID- 24222912 TI - Reducing the complexity of complex gene coexpression networks by coupling multiweighted labeling with topological analysis. AB - Undirected gene coexpression networks obtained from experimental expression data coupled with efficient computational procedures are increasingly used to identify potentially relevant biological information (e.g., biomarkers) for a particular disease. However, coexpression networks built from experimental expression data are in general large highly connected networks with an elevated number of false positive interactions (nodes and edges). In order to infer relevant information, the network must be properly filtered and its complexity reduced. Given the complexity and the multivariate nature of the information contained in the network, this requires the development and application of efficient feature selection algorithms to be able to exploit the topological characteristics of the network to identify relevant nodes and edges. This paper proposes an efficient multivariate filtering designed to analyze the topological properties of a coexpression network in order to identify potential relevant genes for a given disease. The algorithm has been tested on three datasets for three well known and studied diseases: acute myeloid leukemia, breast cancer, and diffuse large B-cell lymphoma. Results have been validated resorting to bibliographic data automatically mined using the ProteinQuest literature mining tool. PMID- 24222913 TI - An update on laboratory diagnosis of liver inherited diseases. AB - Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1 antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID- 24222914 TI - Fullerenols as a new therapeutic approach in nanomedicine. AB - Recently, much attention has been paid to the bioactive properties of water soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today's science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper. PMID- 24222915 TI - The incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population. AB - The aim of this study was to investigate the incidence of hypogonadotropic hypogonadism (HH) in type 2 diabetic men (T2DM) in population of Polish men and examine the possible influence of estradiol levels and glycemic control. We evaluated TT, cfT, estradiol, and glycemic control (HbA1c) in 184 diabetic men and in 149 nondiabetic control group. The mean HbA1c was 8.6 +/- 0.2% and 6.1 +/- 0.3% and cfT concentration was 0.315 +/- 0.08 nmol/L and 0.382 +/- 0.07 nmol/L, respectively. T2DM had higher E2 concentration than nonobese control men (29.4 +/ 3.7 pg/mL versus 24.5 +/- 2.9 pg/mL). Forty-six percent of T2DM were hypogonadal and 93% had HH. We observed inverse relationship between BMI and cfT (r = -0.341, P < 0.01) and positive between BMI and E2 (r = 0.329, P < 0.01). E2 concentration was higher in T2DM with HH versus T2DM with normal TT/cfT concentration (34.5 +/- 5.2 versus 27.4 +/- 3.4 pg/mL). We observed negative correlation between HbA1c and cfT (r = -0.336, P < 0.005) but positive between HbA1c and E2 levels (r = 0.337, P < 0.002). The prevalence of obesity, hypertension, and CVD was higher in men with hypogonadism. High incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population is associated with poor glycemic control and can be secondary to an increase in estradiol concentrations. PMID- 24222916 TI - Lymphedema and therapeutic lymphangiogenesis. AB - Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor. PMID- 24222917 TI - Internalization of B cell receptors in human EU12 MUHC+ immature B cells specifically alters downstream signaling events. AB - It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12 MUHC+ immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12 MUHC+ cells showed impaired Ca2+ flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12 MUHC+ cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12 MUHC+ cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation. PMID- 24222918 TI - Possible mechanisms of fullerene C60 antioxidant action. AB - Novel mechanism of antioxidant activity of buckminsterfullerene C60 based on protons absorbing and mild uncoupling of mitochondrial respiration and phosphorylation was postulated. In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory. Fullerene's geroprotective activity is sufficiently higher than those of the most powerful reactive oxygen species scavengers. We propose here that C60 has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation. This, in turn, leads to the decrease in ROS production. PMID- 24222919 TI - The cytotoxic effect of magainin II on the MDA-MB-231 and M14K tumour cell lines. AB - Many studies have highlighted the tumoricidal properties of some natural peptides known to have antimicrobial virtues. Also, the increasingly higher resistance to conventional antibiotics has become a global public health issue, and the need for new antibiotics has stimulated interest in finding and synthesizing new antimicrobial peptides, which may also be used as chemotherapeutic agents. Relying on the literature, the purpose of our in vitro research was to assess the tumoricidal potential of magainin II on a series of tumour cell lines, namely, MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results of our study revealed that the cytotoxic effects of magainin II depend on its concentration. Its efficiency is significant at 120 MUM concentrations, and, although it is much lower, it persists even at 60 MUM concentrations. The effects were insignificant at 30 MUM concentrations. In our experimental research, the tumoricidal effect of magainin II was not significantly dependent on the type of tumour cell line used. PMID- 24222921 TI - The weather-beaten dorsal hand clinical rating, shadow casting optical profilometry, and skin capacitance mapping. AB - Laypeople commonly perceive some skin xerosis and withering (roughness) changes during winter on some parts of the body, particularly on the dorsal hands. The aim of the study was to assess the withered skin surface changes occurring during the four seasons. A total of 47 menopausal women completed the study. A group of 31 volunteers were on hormone replacement therapy (HRT) and 16 were out of HRT. Skin xerosis and scaliness were rated clinically. In addition, skin whitening was assessed by computerized shadow casting optical profilometry and by skin capacitance mapping. The volunteers were not using topical creams and over-the counter products on their hands. Marked changes, recorded over the successive seasons, corresponded to patchy heterogeneous stratum corneum hydration and heterogeneous skin surface roughness changing over seasons; they likely resulted from changes in the environmental temperature and atmosphere moisture. The severity of the changes revealed by clinical inspection was not supported by similar directions of fluctuations in the instrumental assessments. This seemingly contradiction was in fact due to different levels of scale observation. The clinical centimetric scale and the instrumental inframillimetric scale possibly provide distinct aspects of a given biological impact. PMID- 24222922 TI - Biochemistry and physiological functions of ADAMTS7 metalloprotease. AB - Here, we provide a comprehensive review of current findings concerning the biochemistry and physiological functions of ADAMTS7, a metalloprotease that is known to interact with cartilage oligomeric matrix protein, progranulin, and alpha2-macroglobulin. Such broad substrate specificity and potentially diverse physiological functions make ADAMTS7 an interesting enzyme to study. ADAMTS7 has been shown to play a role in the pathogenesis of arthritis and disc disorders. More recently, the ADAMTS7 locus is identified to have a strong association with coronary atherosclerotic disease. However, the role of ADAMTS7 in the development of atherosclerosis is yet to be determined. The development of an easy and high throughput assay for ADAMTS7 activity and appropriate animal models will allow us to uncover the novel mechanisms of coronary arterial disease. PMID- 24222923 TI - The Community Narration (CN) Approach: Understanding a Group's Identity and Cognitive Constructs through Personal and Community Narratives. AB - Community program evaluations, visioning and assessments must always endeavor to attain useful information in the most sensitive way. Most community-based organizations form, grow and continue on their own without the help of outside experts. Participatory approaches should respect the historical evolution of these groups and understand the positive factors that underlie their organizational beliefs. A group's mission, values and identity should inform any community program evaluation, consulting project, and the design of any research study. Narrative methods have been used with mutual-help groups and many other organizations to good effect. Such methods have great potential to avoid hierarchical and unidirectional forms of evaluation, encouraging the group's collective psychology and identity-based constructs to emerge. We developed a participatory, narrative technique called Community Narration (CN), which is described here. The technique utilizes personal stories and community narratives as an entry into the evaluation process or other work involved in understanding an organization. The community's participants were able to use the technique successfully, found it enriching, and the constructs obtained have led to many discussions and member-guided research related to the organization. PMID- 24222920 TI - Multimodality molecular imaging of stem cells therapy for stroke. AB - Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB), in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI), nuclear medicine imaging, and optical imaging (OI). Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke. PMID- 24222924 TI - Bergman spaces of natural G-manifolds. AB - Let G be a unimodular Lie group, X a compact manifold with boundary, and M the total space of a principal bundle [Formula: see text] so that M is also a strongly pseudoconvex complex manifold. In this work, we show that if there exists a point [Formula: see text] such that [Formula: see text] is contained in the complex tangent space [Formula: see text] of bM at p, then the Bergman space of M is large. Natural examples include the gauged G-complexifications of Heinzner, Huckleberry, and Kutzschebauch. PMID- 24222925 TI - Challenges and opportunities in synthetic biology for chemical engineers. AB - Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. PMID- 24222926 TI - Associations Between Fear of Negative Evaluation and Eating Pathology During Intervention and 12-Month Follow-up. AB - Fear of negative evaluation, a core feature of social anxiety disorder, has been prospectively related to eating pathology over and above other established risk factors, suggesting that it may be an important cognitive risk factor for eating disorders. The present study examined reciprocal longitudinal relations among fear of negative evaluation and eating disorder risk factors using a female undergraduate sample (N=82) enrolled in an eating disorder prevention program. Cross-lagged panel analysis revealed that fear of negative evaluation was a determinant of subsequent body dissatisfaction and eating disorder symptoms. Fear of negative evaluation also predicted subsequent thin-ideal internalization among participants with high BMI, but not among those with low BMI. Fear of negative evaluation did not predict future dietary restraint or negative affect but was itself predicted by prior levels of thin ideal internalization, body dissatisfaction, dietary restraint, and negative affect. Findings suggest that fear of negative evaluation may be a useful target for reducing body image concerns and maladaptive eating behavior. PMID- 24222927 TI - A Phase I Bayesian Adaptive Design to Simultaneously Optimize Dose and Schedule Assignments Both Between and Within Patients. AB - In traditional schedule or dose-schedule finding designs, patients are assumed to receive their assigned dose-schedule combination throughout the trial even though the combination may be found to have an undesirable toxicity profile, which contradicts actual clinical practice. Since no systematic approach exists to optimize intra-patient dose-schedule assignment, we propose a Phase I clinical trial design that extends existing approaches to optimize dose and schedule solely between patients by incorporating adaptive variations to dose-schedule assignments within patients as the study proceeds. Our design is based on a Bayesian non-mixture cure rate model that incorporates multiple administrations each patient receives with the per-administration dose included as a covariate. Simulations demonstrate that our design identifies safe dose and schedule combinations as well as the traditional method that does not allow for intra patient dose-schedule reassignments, but with a larger number of patients assigned to safe combinations. Supplementary materials for this article are available online. PMID- 24222928 TI - A Nonparametric Bayesian Model for Local Clustering with Application to Proteomics. AB - We propose a nonparametric Bayesian local clustering (NoB-LoC) approach for heterogeneous data. NoB-LoC implements inference for nested clusters as posterior inference under a Bayesian model. Using protein expression data as an example, the NoB-LoC model defines a protein (column) cluster as a set of proteins that give rise to the same partition of the samples (rows). In other words, the sample partitions are nested within protein clusters. The common clustering of the samples gives meaning to the protein clusters. Any pair of samples might belong to the same cluster for one protein set but to different clusters for another protein set. These local features are different from features obtained by global clustering approaches such as hierarchical clustering, which create only one partition of samples that applies for all the proteins in the data set. In addition, the NoB-LoC model is different from most other local or nested clustering methods, which define clusters based on common parameters in the sampling model. As an added and important feature, the NoB-LoC method probabilistically excludes sets of irrelevant proteins and samples that do not meaningfully co-cluster with other proteins and samples, thus improving the inference on the clustering of the remaining proteins and samples. Inference is guided by a joint probability model for all the random elements. We provide a simulation study and a motivating example to demonstrate the unique features of the NoB-LoC model. PMID- 24222929 TI - Paramagnetic 19F NMR and Electrospray Ionization Mass Spectrometric Studies of Substituted Pyridine Complexes of Chromium(III): Models for Potential Use of 19F NMR to Probe Cr(III)-Nucleotide Interaction. AB - The synthesis and characterization of chromium basic carboxylate complexes, [Cr3(O2CR)6L3]+, containing trifluoroacetate, 3-fluoropyridine, 3 trifluoromethylpyridine, and 4-trifluoromethylpyridine are described. The substituted pyridine ligands are used as models of DNA bases to determine whether 19F NMR would be a potentially useful probe of the binding of Cr3+ to DNA. The 19F NMR resonances of the coordinated ligands, while broadened by delocalization of unpaired electron density from the S=3/2 chromic centers, are readily discernable, and the contact shifts are of sufficient magnitude that the signals from coordinated and free ligands can easily be differentiated. Thus, 19F NMR appears to be a potentially useful probe of the binding of Cr3+ to DNA containing F-labeled bases. Additionally, electrospray MS is shown to be a convenient method to establish the identity of chromium basic carboxylate assemblies. PMID- 24222930 TI - Structural changes in single membranes in response to an applied transmembrane electric potential revealed by time-resolved neutron/X-ray interferometry. AB - The profile structure of a hybrid lipid bilayer, tethered to the surface of an inorganic substrate and fully hydrated with a bulk aqueous medium in an electrochemical cell, was investigated as a function of the applied transbilayer electric potential via time-resolved neutron reflectivity, enhanced by interferometry. Significant, and fully reversible structural changes were observed in the distal half (with respect to the substrate surface) of the hybrid bilayer comprised of a zwitterionic phospholipid in response to a +100mV potential with respect to 0mV. These arise presumably due to reorientation of the electric dipole present in the polar headgroup of the phospholipid and its resulting effect on the thickness of the phospholipid's hydrocarbon chain layer within the hybrid bilayer's profile structure. The profile structure of the voltage-sensor domain from a voltage-gated ion channel protein within a phospholipid bilayer membrane, tethered to the surface of an inorganic substrate and fully hydrated with a bulk aqueous medium in an electrochemical cell, was also investigated as a function of the applied transmembrane electric potential via time-resolved X-ray reflectivity, enhanced by interferometry. Significant, fully-reversible, and different structural changes in the protein were detected in response to +/-100mV potentials with respect to 0mV. The approach employed is that typical of transient spectroscopy, shown here to be applicable to both neutron and X-ray reflectivity of thin films. PMID- 24222931 TI - Multisensory vocal communication in primates and the evolution of rhythmic speech. AB - The integration of the visual and auditory modalities during human speech perception is the default mode of speech processing. That is, visual speech perception is not a capacity that is "piggybacked" on to auditory-only speech perception. Visual information from the mouth and other parts of the face is used by all perceivers to enhance auditory speech. This integration is ubiquitous and automatic and is similar across all individuals across all cultures. The two modalities seem to be integrated even at the earliest stages of human cognitive development. If multisensory speech is the default mode of perception, then this should be reflected in the evolution of vocal communication. The purpose of this review is to describe the data that reveal that human speech is not uniquely multisensory. In fact, the default mode of communication is multisensory in nonhuman primates as well but perhaps emerging with a different developmental trajectory. Speech production, however, exhibits a unique bimodal rhythmic structure in that both the acoustic output and the movements of the mouth are rhythmic and tightly correlated. This structure is absent in most monkey vocalizations. One hypothesis is that the bimodal speech rhythm may have evolved through the rhythmic facial expressions of ancestral primates, as indicated by mounting comparative evidence focusing on the lip-smacking gesture. PMID- 24222932 TI - Quality assesment of mie 2009 sarajevo conference presentations. AB - INTRODUCTION: XXII European Congress of Medical Informatics (MIe 2009) took place in Sarajevo from August 30th to September 2nd 2009. Assessment of quality of papers presented at MIe 2009 was a process of observation, measurement, comparison and evaluation of the quality of orally presented papers. METHODOLOGY: For this study, and for the first time since EFMI founding (1976) and MIE congresses, the authors introduced a specially created quality assessment form with five relevant paper quality variables (methodological approach, international influence, scientific content, language quality, technical features) which the first author of this article used in peer-review process of papers submitted for publication in the journal Acta Informatica Medica (as Editor-in-Chief for last 18 years). The survey was conducted on the principle of random sampling of participants of MIE 2009 Conference in Sarajevo, where specially trained interviewers (final year students of medicine and engineering at the University of Sarajevo) interviewed 33 session's chairs and 110 participants/listeners of MIE 2009 paper presentations in 33 sessions (of total 40). Data was collected, entered into a specially created database, analyzed and presented. RESULTS: From the total of 150 oral presentations at the MIE 2009, 110 oral presentations were graded by both chairs and participants/ listeners. Grading results were compared and we found that in 60% of cases (66 papers) session chairs gave higher ratings than other participants of the congress. The highest rating was 10, and the lowest 3. Only 3 of the papers received all four grades 10 from the session chairs. The most common grade given by chairs of the session was 8 (26.36%), followed by 7 (20%), 9 (19.32%), 6 (13.18%), 10 and 5 (7.50%), 4 (5%) and 3 (1.14%). Significant differences in quality assessment of papers done by chairs and those done by other participants/listeners are observed. CONCLUSION: This work should demonstrate the importance of introducing universal (uniform) scale for assessment of articles at conferences that would provide objective and relevant assessment, which has not been the practice. Results obtained using a single standardized scale can be compared to each other and thus improve the quality of the articles and the congress. Future congresses can be organized in this manner and become leading events in certain fields of medical science. PMID- 24222933 TI - Telemedicine in anesthesiology and reanimatology. AB - SUMMARY: In recent years impressive progress is happening in information and telecommunication technologies. The application of computers in medicine allows permanent data storage, data transfer from one place to another, retrieving and data processing, data availability at all times, monitoring of patients over time, etc. This can significantly improve the medical profession. Medicine is one of the most intensive users of all types of information and telecommunication technology. Quickly and reliably store and transfer data (text, images, sounds, etc.) provides significant assistance and improvement in almost all medical procedures. In addition, data in locations far from medical centers can be of invaluable benefit, especially in emergency cases in which the decisive role has anesthesiologists. PMID- 24222934 TI - Distance learning perspectives. AB - The development of modern technology and the Internet has enabled the explosive growth of distance learning. distance learning is a process that is increasingly present in the world. This is the field of education focused on educating students who are not physically present in the traditional classrooms or student's campus. described as a process where the source of information is separated from the students in space and time. If there are situations that require the physical presence of students, such as when a student is required to physically attend the exam, this is called a hybrid form of distance learning. This technology is increasingly used worldwide. The Internet has become the main communication channel for the development of distance learning. PMID- 24222935 TI - Statins as modulators of regulatory T-cell biology. AB - Statins are pharmacological inhibitors of the activity of 3-hydroxy-3-methyl glutaryl-CoA reductase (HMGCR), an enzyme responsible for the synthesis of cholesterol. Some recent experimental studies have shown that besides their effects on the primary and secondary prevention of cardiovascular diseases, statins may also have beneficial anti-inflammatory effects through diverse mechanisms. On the other hand, the induction and activity of regulatory T cells (Treg) are key processes in the prevention of pathology during chronic inflammatory and autoimmune diseases. Hence, strategies oriented towards the therapeutic expansion of Tregs are gaining special attention among biomedical researchers. The potential effects of statins on the biology of Treg are of particular importance because of their eventual application as in vivo inducers of Treg in the treatment of multiple conditions. In this paper we review the experimental evidence pointing out to a potential effect of statins on the role of regulatory T cells in different conditions and discuss its potential clinical significance. PMID- 24222936 TI - Mediators of neuroinflammation. PMID- 24222937 TI - The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts. AB - The oxidative modification hypothesis of atherosclerosis, which assigns to oxidized low-density lipoproteins (LDLs) a crucial role in atherosclerosis initiation and progression, is still debated. This review examines the role played by oxidized LDLs in atherogenesis taking into account data derived by studies based on molecular and clinical approaches. Experimental data carried out in cellular lines and animal models of atherosclerosis support the proatherogenic role of oxidized LDLs: (a) through chemotactic and proliferating actions on monocytes/macrophages, inciting their transformation into foam cells; (b) through stimulation of smooth muscle cells (SMCs) recruitment and proliferation in the tunica intima; (c) through eliciting endothelial cells, SMCs, and macrophages apoptosis with ensuing necrotic core development. Moreover, most of the experimental data on atherosclerosis-prone animals benefiting from antioxidant treatment points towards a link between oxidative stress and atherosclerosis. The evidence coming from cohort studies demonstrating an association between oxidized LDLs and cardiovascular events, notwithstanding some discrepancies, seems to point towards a role of oxidized LDLs in atherosclerotic plaque development and destabilization. Finally, the results of randomized clinical trials employing antioxidants completed up to date, despite demonstrating no benefits in healthy populations, suggest a benefit in high-risk patients. In conclusion, available data seem to validate the oxidative modification hypothesis of atherosclerosis, although additional proofs are still needed. PMID- 24222938 TI - Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C? AB - The high rate of sustained viral response (SVR) to boceprevir or telaprevir-based triple therapy in hepatitis C (HCV)-related, non-cirrhotic naive patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used, unlike what is observed with the peginterferon and ribavirin schedules. This concept is strongly expressed by some opinion leaders on the basis of the data derived from sub-analyses of registrative trials as well as from a post-hoc analysis of the phase II C208 clinical trial. The perception of unrestrainable therapeutic success with the use of newer, more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir, an HCV NS5B polymerase inhibitor, as well as by the data from the phase II and III studies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors. However, a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the "world of trials". Furthermore, many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment. Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients, an issue that will hopefully be investigated in further studies. This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents. PMID- 24222939 TI - Transmission of hepatitis C virus: self-limiting hepatitis or chronic hepatitis? AB - It has been suggested that hepatitis C virus (HCV) is selectively transmitted to a new host as an infectious clone from multiple HCV variants (quasispecies) in the donor. Most individuals with HCV infection develop chronic hepatitis, but approximately 15%-40% of them clear the virus spontaneously and the hepatitis is resolved in a self-limiting manner in the acute phase of infection. This difference in the outcome of acute hepatitis C is attributable to both viral characteristics and genetic regulation of infection. In particular, the evolutionary dynamics of the infecting virus and host genetic polymorphisms pertaining mainly to the immune system, including polymorphisms in the region of the Interleukin 28B gene encoding interferon-lambda-3, are associated with susceptibility to HCV infection. PMID- 24222940 TI - New progress in endoscopic treatment of esophageal diseases. AB - The technique of endoscopic submucosal dissection (ESD), which was developed for en bloc resection of large lesions in the stomach, has been widely accepted for the treatment of the entire gastrointestinal tract. Many minimally invasive endoscopic therapies based on ESD have been developed recently. Endoscopic submucosal excavation, submucosal tunneling endoscopic resection and laparoscopic endoscopic cooperative surgery have been used to remove submucosal tumors, especially tumors which originate from the muscularis propria of the digestive tract. Peroral endoscopic myotomy has recently been described as a scarless and less invasive surgical myotomy option for the treatment of achalasia. Patients benefit from minimally invasive endoscopic therapy. This article, in the highlight topic series, provides detailed information on the indications and treatments for esophageal diseases. PMID- 24222941 TI - PNPLA3 I148M polymorphism and progressive liver disease. AB - The 148 Isoleucine to Methionine protein variant (I148M) of patatin-like phospholipase domain-containing 3 (PNPLA3), a protein is expressed in the liver and is involved in lipid metabolism, has recently been identified as a major determinant of liver fat content. Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver: from simple steatosis to steatohepatitis and progressive fibrosis. Furthermore, the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis, and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly chronic hepatitis B virus hepatitis, hereditary hemochromatosis and primary sclerosing cholangitis. All in all, studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases. Remarkably, the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation, suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes, directly promoting fibrogenesis. Therefore, PNPLA3 is a key player in liver disease progression. Assessment of the I148M polymorphism will possibly inform clinical practice in the future, whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis. PMID- 24222942 TI - Peritoneal carcinomatosis. AB - Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease. PMID- 24222944 TI - Potential role of Helicobacter pylori infection in nonalcoholic fatty liver disease. AB - Accumulating evidence has implicated Helicobacter pylori (H. pylori) infection in extragastrointestinal diseases, including obesity, type 2 diabetes mellitus, cardiovascular disease, and liver disease. Recently, there has been a special focus on H. pylori infection as a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is currently considered to be the most common liver disorder in western countries, and is rapidly becoming a serious threat to public health. The mechanisms of pathogenesis underlying NAFLD remain unclear at present and therapeutic options are limited. The growing awareness of the role of H. pylori in NAFLD is thus important to aid the development of novel intervention and prevention strategies, because the eradication of H. pylori is easy and much less expensive than long-term treatment of the other risk factors. H. pylori infection is involved in the pathogenesis of insulin resistance (IR), which is closely linked with NAFLD. It provides a new insight into the pathogenesis of NAFLD. This review probes the possible relationship between H. pylori and NAFLD, from the perspective of the potential mechanism of how H. pylori infection brings about IR and other aspects concerning this correlation. PMID- 24222946 TI - Presence of phthalates in gastrointestinal medications: is there a hidden danger? AB - Pharmaceutical companies that produce gastrointestinal (GI) medications often utilize phthalates for their ability to localize medication release. Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates, proton pump inhibitors, and pancreatic enzymes. Our understanding of the cumulative health effects of phthalates from medications remains unclear, and there is increasing evidence that phthalates are not harmless. Experimental studies in animals have shown that phthalates, specifically dibutyl phthalate and Di-(2-ethyl-hexyl) phthalate, have the potential to alter and/or inhibit reproductive biology and in utero development. Despite the lack of definitive human data, many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status, specifically developmental problems. Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences. It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements, specifically in pregnant woman with inflammatory bowel disease. PMID- 24222945 TI - Stages based molecular mechanisms for generating cholangiocytes from liver stem/progenitor cells. AB - Except for the most organized mature hepatocytes, liver stem/progenitor cells (LSPCs) can differentiate into many other types of cells in the liver including cholangiocytes. In addition, LSPCs are demonstrated to be able to give birth to other kinds of extra-hepatic cell types such as insulin-producing cells. Even more, under some bad conditions, these LSPCs could generate liver cancer stem like cells (LCSCs) through malignant transformation. In this review, we mainly concentrate on the molecular mechanisms for controlling cell fates of LSPCs, especially differentiation of cholangiocytes, insulin-producing cells and LCSCs. First of all, to certificate the cell fates of LSPCs, the following three features need to be taken into account to perform accurate phenotyping: (1) morphological properties; (2) specific markers; and (3) functional assessment including in vivo transplantation. Secondly, to promote LSPCs differentiation, systematical attention should be paid to inductive materials (such as growth factors and chemical stimulators), progressive materials including intracellular and extracellular signaling pathways, and implementary materials (such as liver enriched transcriptive factors). Accordingly, some recommendations were proposed to standardize, optimize, and enrich the effective production of cholangiocyte like cells out of LSPCs. At the end, the potential regulating mechanisms for generation of cholangiocytes by LSPCs were carefully analyzed. The differentiation of LSPCs is a gradually progressing process, which consists of three main steps: initiation, progression and accomplishment. It's the unbalanced distribution of affecting materials in each step decides the cell fates of LSPCs. PMID- 24222943 TI - Quasispecies structure, cornerstone of hepatitis B virus infection: mass sequencing approach. AB - Hepatitis B virus (HBV) is a DNA virus with complex replication, and high replication and mutation rates, leading to a heterogeneous viral population. The population is comprised of genomes that are closely related, but not identical; hence, HBV is considered a viral quasispecies. Quasispecies variability may be somewhat limited by the high degree of overlapping between the HBV coding regions, which is especially important in the P and S gene overlapping regions, but is less significant in the X and preCore/Core genes. Despite this restriction, several clinically and pathologically relevant variants have been characterized along the viral genome. Next-generation sequencing (NGS) approaches enable high-throughput analysis of thousands of clonally amplified regions and are powerful tools for characterizing genetic diversity in viral strains. In the present review, we update the information regarding HBV variability and present a summary of the various NGS approaches available for research in this virus. In addition, we provide an analysis of the clinical implications of HBV variants and their study by NGS. PMID- 24222947 TI - Neuromodulation for fecal incontinence: an effective surgical intervention. AB - Fecal incontinence is a disabling symptom with medical and social implications, including fear, embarrassment, isolation and even depression. Most patients live in seclusion and have to plan their life around the symptom, with secondary impairment of their quality of life. Conservative management and biofeedback therapy are reported to benefit a good percentage of those affected. However, surgery must be considered in the non-responder population. Recently, sacral nerve electrostimulation, lately named neuromodulation, has been reported to benefit patients with fecal incontinence in randomized controlled trials more than placebo stimulation and conservative management, by some unknown mechanism. Neuromodulation is a minimally invasive procedure with a low rate of adverse events and apparently favorable cost-efficacy profile. This review is intended to expand knowledge about this effective intervention among the non-surgically skilled community who deals with this disabled group of patients. PMID- 24222948 TI - Interaction of IFNL3 with insulin resistance, steatosis and lipid metabolism in chronic hepatitis C virus infection. AB - Metabolic changes are inextricably linked to chronic hepatitis C (CHC). Recently polymorphisms in the IFNL3 (IL28B) region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus (HCV) infection. Further, circumstantial evidence suggests a link between IFNL3 single nucleotide polymorphisms and lipid metabolism, steatosis and insulin resistance in CHC. The emerging picture suggests that the responder genotypes of IFNL3 polymorphisms are associated with a higher serum lipid profile, and less frequent steatosis and insulin resistance. This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression. PMID- 24222949 TI - Gastrointestinal complications of systemic sclerosis. AB - Systemic sclerosis is an autoimmune disease characterized by progressive skin thickening and tightness. Pulmonary interstitial fibrosis and kidney damage are the most important indicators for mortality; however, the gastrointestinal tract is the most commonly damaged system. Virtually all parts of the gastrointestinal (GI) tract can be involved, although the esophagus is the most frequently reported. The mechanisms that cause such extensive damage are generally unclear, but vascular changes, immunological abnormalities, excessive accumulation of collagen in the submucosa, smooth muscle atrophy and neuropathy may participate because these are the most common histological findings in biopsies and autopsies. Most patients with GI tract involvement complain about dyspepsia, nausea, vomiting, abdominal bloating/distension, and fecal incontinence. These symptoms are generally mild during the early stage of the disease and are likely ignored by physicians. As the disease becomes more advanced, however, patient quality of life is markedly influenced, whereby malnutrition and shortened survival are the usual consequences. The diagnosis for systemic sclerosis is based on manometry measurements and an endoscopy examination. Supportive and symptomatic treatment is the main therapeutic strategy; however, an early diagnosis is critical for successful management. PMID- 24222950 TI - Advances in the management of acute liver failure. AB - Acute liver failure (ALF) is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver. The causes of ALF encompass a wide variety of toxic, viral, metabolic, vascular and autoimmune insults to the liver, and identifying the correct cause can be difficult or even impossible. Many patients with ALF develop a cascade of serious complications involving almost every organ system, and death is mostly due to multi-organ failure, hemorrhage, infection, and intracranial hypertension. Fortunately, the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology, and the advanced intensive care management. For most severely affected patients who fail to recover after treatment, rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop. This review focuses on the recent advances in the understanding of various contributing etiologies, the administration of etiology specific treatment to alleviate the liver injury, and the management of complications (e.g., encephalopathy, coagulopathy, cardiovascular instability, respiratory failure, renal failure, sepsis and metabolic disturbance) in patients with ALF. Assessment of the need for liver transplantation is also presented. PMID- 24222951 TI - Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. AB - AIM: To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein expression. METHODS: Array technologies were used to generate 1146 microRNAs and 124 proteins expression profiles of samples from 60 patients with gastric cancer. For the integrative analysis, we used established mRNA expression data published in our previous study. Whole mRNA expression levels were acquired from microarray data for 60 identical gastric cancer patients. Two gastric adenocarcinoma subgroups with distinct mRNA expression profiles presented distinctly different prognoses. MicroRNA and protein expression patterns were compared between gastric cancer tissue and normal gastric tissue and between two different prognostic groups. Aberrantly expressed microRNA, associated mRNA, and protein in patients with poor-prognosis gastric cancer were validated by quantitative reverse transcription polymerase chain reaction and immunochemistry in independent patients. RESULTS: We obtained the expression data of 1146 microRNAs and 124 cancer-related proteins. Four microRNAs were aberrantly expressed in the two prognostic groups and in cancer vs non cancer tissues (P < 0.05). In the poor-prognosis group, miR-196b, miR-135b, and miR-93 were up-regulated and miR-29c* was down-regulated. miR-196b expression positively correlated with Homeobox A10 (HOXA10) expression (r = 0.726, P < 0.001), which was significantly increased in poor-prognosis patients (P < 0.001). Comparing gastric cancer with non-cancer tissues, 46/124 proteins showed differential expression (P < 0.05); COX2 (P < 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group. CONCLUSION: Co activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. Elucidation of the biologic function of miR-196b and HOXA10 is warranted. PMID- 24222952 TI - Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett's esophagus. AB - AIM: To determine whether magnified observation of short-segment Barrett's esophagus (BE) is useful for the detection of specialized intestinal metaplasia (SIM). METHODS: Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to * 80. The magnified images were analyzed with respect to their pit-patterns, which were simultaneously classified into five epithelial types [I (small round), II (straight), III (long oval), IV (tubular), V (villous)] by Endo's classification. Then, a 0.5% solution of methylene blue (MB) was sprayed over columnar mucosa. The patterns of the magnified image and MB staining were analyzed. Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy. RESULTS: Three of five patients with a type V (villous) epithelial pattern had SIM, whereas 21 patients with a non-type V epithelial patterns did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pit-patterns in detecting SIM were 100%, 91.3%, 92.3%, 60% and 100%, respectively (P = 0.004). Three of the 12 patients with positive MB staining had SIM, whereas 14 patients with negative MB staining did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MB staining in detecting SIM were 100%, 60.9%, 65.4%, 25% and 100%, respectively (P = 0.085). The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar's test (P = 0.0391). CONCLUSION: The magnified observation of a short-segment BE according to the mucosal pattern and its classification can be predictive of SIM. PMID- 24222953 TI - C/EBP homologous protein deficiency aggravates acute pancreatitis and associated lung injury. AB - AIM: To investigate the pathophysiological role of C/EBP homologous protein (CHOP) in severe acute pancreatitis and associated lung injury. METHODS: A severe acute pancreatitis model was induced with 6 injections of cerulein (Cn, 50 MUg/kg) at 1-h intervals, then intraperitoneal injection of lipopolysaccharide (LPS, 7.5 mg/kg) in CHOP-deficient (Chop(-/-)) mice and wild-type (WT) mice. Animals were sacrificed under anesthesia, 3 h or 18 h after LPS injection. Serum amylase, lipase, and cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha], pathological changes, acute lung injury, and apoptosis in the pancreas were evaluated. Serum amylase and lipase activities were detected using a medical automatic chemical analyzer. Enzyme-linked immunosorbent assay kits were used to evaluate TNF-alpha and IL-6 levels in mouse serum and lung tissue homogenates. Apoptotic cells in sections of pancreatic tissues were determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) analysis. The mouse carotid arteries were cannulated and arterial blood samples were collected for PaO2 analysis. The oxygenation index was expressed as PaO2/FiO2. RESULTS: Administration of Cn and LPS for 9 and 24 h induced severe acute pancreatitis in Chop(-/-) and WT mice. When comparing Chop(-/-) mice and WT mice, we observed that CHOP-deficient mice had greater increases in serum TNF alpha (214.40 +/- 19.52 pg/mL vs 150.40 +/- 16.70 pg/mL; P = 0.037), amylase (4236.40 +/- 646.32 U/L vs 2535.30 +/- 81.83 U/L; P = 0.041), lipase (1678.20 +/- 170.57 U/L vs 1046.21 +/- 35.37 U/L; P = 0.008), and IL-6 (2054.44 +/- 293.81 pg/mL vs 1316.10 +/- 108.74 pg/mL; P = 0.046) than WT mice. The histopathological changes in the pancreases and lungs, decreased PaO2/FiO2 ratio, and increased TNF alpha and IL-6 levels in the lungs were greater in Chop(-/-) mice than in WT mice (pancreas: Chop(-/-) vs WT mice, hemorrhage, P = 0.005; edema, P = 0.005; inflammatory cells infiltration, P = 0.005; total scores, P = 0.006; lung: hemorrhage, P = 0.017; edema, P = 0.017; congestion, P = 0.017; neutrophil infiltration, P = 0.005, total scores, P = 0.001; PaO2/FiO2 ratio: 393 +/- 17.65 vs 453.8, P = 0.041; TNF-alpha: P = 0.043; IL-6, P = 0.040). Results from TUNEL analysis indicated increased acinar cell apoptosis in mice following the induction of acute pancreatitis. However, Chop(-/-) mice displayed significantly reduced pancreatic apoptosis compared with the WT mice (201.50 +/- 31.43 vs 367.00 +/- 47.88, P = 0.016). CONCLUSION: These results suggest that CHOP can exert protective effects against acute pancreatitis and limit the spread of inflammatory damage to the lungs. PMID- 24222954 TI - Photodynamic therapy vs radiofrequency ablation for Barrett's dysplasia: efficacy, safety and cost-comparison. AB - AIM: To compare effectiveness, safety, and cost of photodynamic therapy (PDT) and radiofrequency ablation (RFA) in treatment of Barrett's dysplasia (BD). METHODS: Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared. Thirty-three patients with high-grade dysplasia (HGD) had treatment with porfimer sodium photosensitzer and 630 nm laser (130 J/cm), with maximum of 3 treatment sessions. Fifty-three patients with BD (47 with low-grade dysplasia -LGD, 6 with HGD) had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions. Both groups received proton pump inhibitors twice daily. Endoscopic biopsies were acquired at 2 and 12 mo after enrollment, with 4 quadrant biopsies every 1 cm of the original BE extent. A complete histological resolution response of BD (CR-D) was defined as all biopsies at the last endoscopy session negative for BD. Fisher's exact test was used to assess differences between the two study groups for primary outcomes. For all outcomes, a two-sided P value of less than 0.05 was considered to indicate statistical significance. RESULTS: Thirty (91%) PDT patients and 39 (74%) RFA were men (P = 0.05). The mean age was 70.7 +/- 12.2 and 65.4 +/- 12.7 (P = 0.10) year and mean length of BE was 5.4 +/- 3.2 cm and 5.7 +/- 3.2 cm (P = 0.53) for PDT and RFA patients, respectively. The CR-D was (18/33) 54.5% with PDT vs (47/53) 88.7% with RFA (P = 0.001). One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA. PDT was five times more costly than RFA at our institution. The two groups were not randomized and had different BD grading are the limitations of the study. CONCLUSION: In our experience, RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD. PMID- 24222955 TI - Children with celiac disease and high tTGA are genetically and phenotypically different. AB - AIM: To investigate whether celiac disease (CD) patients with tissue transglutaminase antibody (tTGA) >= 100 U/mL are different from patients with lower tTGA levels. METHODS: Biopsy-proven (Marsh III) pediatric CD patients (n = 116) were prospectively included between March 2009 and October 2012. The biopsies were evaluated by a single pathologist who was blinded to all of the patients' clinical data. The patients were distributed into 2 groups according to their tTGA level, which was measured using enzyme-linked immunoassay: tTGA >= 100 U/mL and tTGA < 100 U/mL. The patients'characteristics, symptoms, human leukocyte antigen (HLA) genotype and degree of histological involvement were compared between the 2 groups. RESULTS: A total of 34 (29.3%) children had tTGA values < 100 U/mL and 82 (70.7%) tTGA levels of >= 100 U/mL. Patients with high tTGA levels had lower average body weight-for-height standard deviation scores (SDS) than did patients with tTGA < 100 U/mL (-0.20 +/- 1.19 SDS vs 0.23 +/- 1.03 SDS, P = 0.025). In the low tTGA group, gastrointestinal symptoms were more common (97.1% vs 75.6%, P = 0.006). More specifically, abdominal pain (76.5% vs 51.2%; P = 0.012) and nausea (17.6% vs 3.7%, P = 0.018) were more frequent among patients with low tTGA. In contrast, patients with solely extraintestinal manifestations were only present in the high tTGA group (18.3%, P = 0.005). These patients more commonly presented with aphthous stomatitis (15.9% vs 0.0%, P = 0.010) and anemia (32.9% vs 11.8%, P = 0.019). In addition, when evaluating the number of CD associated HLA-DQ heterodimers (HLA-DQ2.5, HLA-DQ2.2 and HLA-DQ8), patients with low tTGA levels more commonly had only 1 disease-associated heterodimer (61.8% vs 31.7%, P = 0.005), while patients with high tTGA more commonly had multiple heterodimers. Finally, patients with tTGA >= 100 U/mL more often had a Marsh IIIc lesion (73.2% vs 20.6%, P < 0.001) while in patients with low tTGA patchy lesions were more common (42.4% vs 6.8%, P < 0.001). CONCLUSION: Patients with tTGA >= 100 U/mL show several signs of more advanced disease. They also carry a larger number of CD associated HLA-DQ heterodimers. PMID- 24222956 TI - Reference genes for quantitative RT-PCR data in gastric tissues and cell lines. AB - AIM: To evaluate the suitability of reference genes in gastric tissue samples and cell lines. METHODS: The suitability of genes ACTB, B2M, GAPDH, RPL29, and 18S rRNA was assessed in 21 matched pairs of neoplastic and adjacent non-neoplastic gastric tissues from patients with gastric adenocarcinoma, 27 normal gastric tissues from patients without cancer, and 4 cell lines using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The ranking of the best single and combination of reference genes was determined by NormFinder, geNormTM, BestKeeper, and DataAssistTM. In addition, GenEx software was used to determine the optimal number of reference genes. To validate the results, the mRNA expression of a target gene, DNMT1, was quantified using the different reference gene combinations suggested by the various software packages for normalization. RESULTS: ACTB was the best reference gene for all gastric tissues, cell lines and all gastric tissues plus cell lines. GAPDH + B2M or ACTB + B2M was the best combination of reference genes for all the gastric tissues. On the other hand, ACTB + B2M was the best combination for all the cell lines tested and was also the best combination for analyses involving all the gastric tissues plus cell lines. According to the GenEx software, 2 or 3 genes were the optimal number of references genes for all the gastric tissues. The relative quantification of DNMT1 showed similar patterns when normalized by each combination of reference genes. The level of expression of DNMT1 in neoplastic, adjacent non-neoplastic and normal gastric tissues did not differ when these samples were normalized using GAPDH + B2M (P = 0.32), ACTB + B2M (P = 0.61), or GAPDH + B2M + ACTB (P = 0.44). CONCLUSION: GAPDH + B2M or ACTB + B2M is the best combination of reference gene for all the gastric tissues, and ACTB + B2M is the best combination for the cell lines tested. PMID- 24222957 TI - Impact of cirrhosis on surgical outcome after pancreaticoduodenectomy. AB - AIM: To elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with liver cirrhosis. METHODS: We studied retrospectively all patients who underwent PD in our centre between January 2002 and December 2011. Group A comprised patients with cirrhotic livers, and Group B comprised patients with non cirrhotic livers. The cirrhotic patients had Child-Pugh classes A and B (patient's score less than 8). Preoperative demographic data, intra-operative data and postoperative details were collected. The primary outcome measure was hospital mortality rate. Secondary outcomes analysed included duration of the operation, postoperative hospital stay, postoperative morbidity and survival rate. RESULTS: Only 67/442 patients (15.2%) had cirrhotic livers. Intraoperative blood loss and blood transfusion were significantly higher in group A (P = 0.0001). The mean surgical time in group A was significantly longer than that in group B (P = 0.0001). Wound complications (P = 0.02), internal haemorrhage (P = 0.05), pancreatic fistula (P = 0.02) and hospital mortality (P = 0.0001) were significantly higher in the cirrhotic patients. Postoperative stay was significantly longer in group A (P = 0.03). The median survival was 19 mo in group A and 24 mo in group B. Portal hypertension (PHT) was present in 16/67 cases of cirrhosis (23.9%). The intraoperative blood loss and blood transfusion were significantly higher in patients with PHT (P = 0.001). Postoperative morbidity (0.07) and hospital mortality (P = 0.007) were higher in cirrhotic patients with PHT. CONCLUSION: Patients with periampullary tumours and well compensated chronic liver disease should be routinely considered for PD at high volume centres with available expertise to manage liver cirrhosis. PD is associated with an increased risk of postoperative morbidity in patients with liver cirrhosis; therefore, it is only recommended in patients with Child A cirrhosis without portal hypertension. PMID- 24222958 TI - Complications and survival in patients undergoing colonic stenting for malignant obstruction. AB - AIM: To investigate whether predicting patients that might be at a higher risk for complications might serve to improve the selection of patients undergoing colonic stenting. METHODS: A retrospective review of consecutive patients who underwent an attempted self-expandable metal stent (SEMS) insertion for malignant colonic obstruction between November 2006 and March 2013. All patients were either referred for preoperative colonic decompression with the intent of a single surgical procedure, or for palliation of the malignant colorectal obstruction for unresectable cancer. Fisher's test or chi(2) test was performed on categorical variables, and the t test for continuous variables. Univariable and multivariable logistic regression were used to examine the association between independent variables and the presence of complications from SEMS insertion. RESULTS: SEMS insertion was attempted in 73 patients. Males comprised 55.71% and the mean age was 67.41 +/- 12.41 years. Of these, 65.15% underwent subsequent surgery, while 34.85% received SEMS as palliation for advanced disease. Extracolonic tumors were only 4.76%. The majority of patients had stage IV disease (63.83%), while the remainder had stage III (36.17%). SEMS were successfully inserted in 93.85% (95%CI: 87.85%-99.85%). Perforations occurred in 4.10%, SEMS migration in 8.21%, and stent re-occlusion from ingrowth occurred in 2.74% of patients. The mean duration of follow up for the patients was 13.52 +/- 17.48 mo (range 0-73 mo). None of the variables: age, sex, time between the onset of symptoms to SEMS insertion, time between SEMS insertion and surgery, length of the stenosis, location of the stenosis, albumin level, or receiving neoadjuvant chemotherapy, could predict the development of complications from either SEMS insertion nor prolonged survival. CONCLUSION: None of the variables could predict the development of complications or survival. Further studies are required to identify patients who would benefit the most from SEMS. PMID- 24222959 TI - Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions. AB - AIM: To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging (AFI) system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion. METHODS: From January 2013 to April 2013, consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study. All lesions were evaluated using a novel AFI system, and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification. The green/red (G/R) ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures. RESULTS: A total of 88 patients with 163 lesions were enrolled in this study. There were significant differences in the G/R ratios of hyperplastic polyps (non-neoplastic lesions), adenoma/intramucosal cancer/submucosal (SM) superficial cancer, and SM deep cancer (P < 0.0001). The mean +/- SD G/R ratios were 0.984 +/- 0.118 in hyperplastic polyps and 0.827 +/- 0.081 in neoplastic lesions. The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions (P < 0.001). When a G/R ratio cut-off value of > 0.89 was applied to determine non-neoplastic lesions, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 83.9%, 82.6%, 53.1%, 95.6% and 82.8%, respectively. For neoplastic lesions, the mean G/R ratio was 0.834 +/- 0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746 +/- 0.045 in SM deep cancer. The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer (P < 0.01). When a G/R ratio cut off value of < 0.77 was applied to distinguish SM deep cancers, the sensitivity, specificity, PPV, NPV, and accuracy were 80.0%, 84.4%, 29.6%, 98.1% and 84.1%, respectively. CONCLUSION: The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion. PMID- 24222960 TI - Characteristics and prognosis of synchronous multiple early gastric cancer. AB - AIM: To assess the clinicopathologic characteristics, risk factors, and prognosis for synchronous multiple early gastric cancer (SMGC). METHODS: A total of 146 patients with SMGC and 1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival. Tumors were classified into groups on the basis of location and histology. Smoking habits were evaluated using the Brinkman index. Clinical and pathological factors were compared using either Fisher's exact test or Pearson's chi(2) test. Logistic regression analysis was performed to identify independent risk factors. Survival rate was calculated using the Kaplan-Meier method. RESULTS: SMGCs accounted for 10.9% of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers. These tumors were typically macroscopically elevated and histologically differentiated. There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location, tumor size, lymph node metastasis, the number of metastatic lymph nodes, venous invasion, or tumor stage (P = 0.052, P = 0.347, P = 0.595, P = 0.805, P = 0.559, and P = 0.408, respectively). Further, there was no significant difference in postoperative survival between the patient groups (P = 0.200). Of the 146 SMGC patients, a single patient had remnant cancer. CONCLUSION: A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC, and minimally invasive treatment may be indicated in some cases. PMID- 24222961 TI - Forward-viewing endoscopic ultrasound-guided NOTES interventions: a study on peritoneoscopic potential. AB - AIM: To evaluate the feasibility of diagnostic and therapeutic transgastric (TG) peritoneoscopic interventions with a forward-viewing endoscopic ultrasound (FV EUS). METHODS: This prospective endoscopic experimental study used an animal model. Combined TG peritoneoscopic interventions and EUS examination of the intra abdominal organs were performed using an FV-EUS on 10 animal models (1 porcine and 9 canine). The procedures carried out include EUS evaluation and endoscopic biopsy of intraperitoneal organs, EUS-guided fine needle aspiration (EUS-FNA), EUS-guided radiofrequency ablation (EUS-RFA), and argon plasma coagulation (APC) for hemostatic control. The animals were kept alive for 7 d, and then necropsy was performed to evaluate results and complications. RESULTS: In all 10 animals, TG peritoneoscopy, followed by endoscopic biopsy for the liver, spleen, abdominal wall, and omentum, was performed successfully. APC helped control minor bleeding. Visualization of intra-abdominal solid organs with real-time EUS was accomplished with ease. Intraperitoneal EUS-FNA was successfully performed on the liver, spleen, and kidney. Similarly, a successful outcome was achieved with EUS-RFA of the hepatic parenchyma. No adverse events were recorded during the study. CONCLUSION: Peritoneoscopic natural orifice transluminal endoscopic surgery (NOTES) interventions through FV-EUS were feasible in providing evaluation and performing endoscopic procedures. It promises potential as a platform for future EUS-based NOTES. PMID- 24222962 TI - Endoscopic papillary large balloon dilation in patients with periampullary diverticula. AB - AIM: To evaluate the safety and effectiveness of endoscopic papillary large balloon dilation (EPLBD) for bile duct stone extraction in patients with periampullary diverticula. METHODS: The records of 223 patients with large common bile duct stones (>= 10 mm) who underwent EPLBD (12-20 mm balloon diameter) with or without limited endoscopic sphincterotomy (ES) from July 2006 to April 2011 were retrospectively reviewed. Of these patients, 93 (41.7%) had periampullary diverticula (PAD), which was categorized into three types. The clinical variables of EPLBD with limited ES (EPLBD + ES) and EPLBD alone were analyzed according to the presence of PAD. RESULTS: Patients with PAD were significantly older than those without (75.2 +/- 8.8 years vs 69.7 +/- 10.9 years, P = 0.000). The rates of overall stone removal and complete stone removal in the first session were not significantly different between the PAD and non-PAD groups, however, there was significantly less need for mechanical lithotripsy in the PAD group (3.2% vs 11.5%, P = 0.026). Overall stone removal rates, complete stone removal rates in the first session and the use of mechanical lithotripsy were not significantly different between EPLBD + ES and EPLBD alone in patients with PAD (96.6% vs 97.1%; 72.9% vs 88.2%; and 5.1% vs 0%, respectively). No significant differences with respect to the rates of pancreatitis, perforation, and bleeding were observed between EPLBD + ES and EPLBD alone in the PAD group (3.4% vs 14.7%, P = 0.095; 0% vs 0%; and 3.4% vs 8.8%, P = 0.351, respectively). CONCLUSION: EPLBD with limited ES and EPLBD alone are safe and effective modalities for common bile duct stone removal in patients with PAD, regardless of PAD subtypes. PMID- 24222963 TI - Quantification of pancreatic exocrine function of chronic pancreatitis with secretin-enhanced MRCP. AB - AIM: To obtain reference values for pancreatic flow output rate (PFR) and peak time (PT) in healthy volunteers and chronic pancreatitis (CP); to correlate quantification of secretin enhanced magnetic resonance cholangiopancreatography (SMRCP) of pancreatic fluid output following secretin with fecal elastase-1 (FE 1) tests. METHODS: The present study includes 53 subjects comprised of 17 healthy individuals and 36 patients with CP from April 2011 to January 2013. The 36 patients with CP were divided into three groups of mild CP (n = 14), moderate CP (n = 19) and advanced CP (n = 3) by M-ANNHEIM classification for CP.. Fifty-three cases underwent FE-1 test and magnetic resonance imaging using 3.0 T-device (Signa EXCITE, GE Healthcare). Coronal T2-weighted single-shot turbo spin-echo, spiratory triggered, covering the papillae, duodenum and small bowel. MRCP was performed with a heavily T2-weighted fat-suppressed long TE HASTE sequence (thick slab 2D MRCP sequence), repeated every 2 min up to 11 min after 0.1 mL/kg secretin injection (Secrelux, Sanochemia((r)), Germany). FE-1 test used sandwich enzyme-linked immunosorbent assay (ELISA) test (ScheBo. Tech((r)), Germany). RESULTS: A good linear correlation showed between the calculated volume and the actual volume by Phantom experiments. Fifty-three paired Quantification of secretin enhanced magnetic resonance cholangiopancreatography (MRCPQ) and FE-1 data sets were analyzed. The mean FE-1 of 53 cases was 525.41 +/- 94.44 MUg/g for 17 healthy volunteers, 464.95 +/- 136.13 MUg/g for mild CP, 301.55 +/- 181.55 MUg/g for moderate CP, 229.30 +/- 146.60 MUg/g for advanced CP. Also, there was statistically significant difference in FE-1 (P = 0.0001) between health and CP. The mean values of PFR and PT were 8.18 +/- 1.11 mL/min, 5.76 +/- 1.71 min for normal; 7.27 +/- 2.04 mL/min, 7.71 +/- 2.55 min for mild CP; 4.98 +/- 2.57 mL/min, 9.10 +/- 3.00 min for moderate CP; 4.13 +/- 1.83 mL/min, 12.33 +/- 1.55 min for advanced CP. Further, statistically significant difference in PFR (P = 0.0001) and PT (P = 0.0001) was observed between health and CP. Besides, there was correlation (r = 0.79) and consistency (K = 0.6) between MRCPQ and ELISA Test. It was related between M-ANNHEIM classification and PFR (r = 0.55), FE-1 (r = 0.57). CONCLUSION: SMRCP can provide a safe, non-invasive and efficient method to evaluate the exocrine function of the pancreas. PMID- 24222964 TI - Clinical features and prognosis in colorectal cancer patients with different ethnicities in Northwest China. AB - AIM: To compare the clinical factors and tumor characteristics that predict survival in colorectal cancer (CRC) patients with different ethnicities in Xin Jiang area. METHODS: A total of 1421 histopathologically confirmed sporadic CRC patients who were either Han/Chinese or Uyghur were identified and enrolled from a database of both diagnoses and operative procedures from Xin Jiang Tumor Hospital, which is affiliated to Xin Jiang Medical University between 2000 and 2007. Patients with family histories of CRC, hereditary nonpolyposis CRC, familial adenomatous polyposis, inflammatory bowel disease, carcinoid, squamous carcinoma or melanoma were excluded. The two ethnic groups were compared with regard to clinical features, tumor characteristics, disease stage, overall survival rate, disease-free survival rate and cancer-specific survival rate. The factors predicting long-term survival were assessed via both univariate and multivariate analysis. RESULTS: Among the 1421 patients with CRC enrolled in this study, 1210 patients were Han/Chinese (mean age, 62.3 +/- 4.5 years; range, 19-92 years), while 211 patients were Uyghur (mean age, 52.4 +/- 15.6 years; range, 17 87 years). There were significant differences in proportions of gender, age, blood type, occupation and histopathological type between the Han/Chinese and Uyghur patients (P < 0.05). The median overall, disease-free and cancer-specific survival time were 45, 62 and 65 mo for the Han/Chinese patients and 42, 49 and 61 mo for the Uyghur patients (P = 0.000, P = 0.005, P = 0.007). The cumulative 5 year survival of the Uyghur patients was significantly worse than that of the Han patients (P = 0.000). A multivariate analysis showed that age, ethnicity, histopathological type, differentiation, T (Infiltration depth), N (Lymph node metastasis), staging, postoperative metastasis and metastatic site (P < 0.05) were found to be the prognostic factors. CONCLUSION: The Uyghur CRC patients are associated with significantly younger age, more aggressive histopathologic characteristics and have significantly worse prognosis than the Han/Chinese patients. PMID- 24222965 TI - Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: a meta-analysis. AB - AIM: To assess diagnostic accuracy of Ras association domain family 1A (RASSF1A) promoter methylation in body fluids (serum, plasma and whole blood) for hepatocellular carcinoma (HCC). METHODS: Relative information about study characteristics and incidence of RASSF1A methylation was collected. Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity were pooled using a random-effect model, and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance. Positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) with 95%CI were also calculated. Meta-regression was applied to analyze observed heterogeneity, and Deeks' test was performed to detect publication bias. RESULTS: After a systematic literature review, seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis. The pooled sensitivity and specificity were 0.70 (95%CI: 0.49-0.85) and 0.72 (95%CI: 0.54-0.85), respectively. The PLR was 2.51 (95%CI: 1.64-3.86), NLR was 0.41 (95%CI: 0.25 0.68), and DOR was 6.13 (95%CI: 3.17-11.84). The chi(2) values of sensitivity, specificity, PLR, NLR and DOR were 59.41 (P < 0.001), 50.50 (P < 0.001), 17.40 (P = 0.010), 31.24 (P < 0.001) and 80.51 (P < 0.001), respectively. The area under the curve was 0.77 (95%CI: 0.73-0.81). Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity (P > 0.05). No significant publication bias was detected by Deeks' test (P = 0.346). CONCLUSION: We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with the alpha-fetoprotein test. PMID- 24222967 TI - Spontaneous intramural duodenal hematoma in type 2B von Willebrand disease. AB - Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction. Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children, but spontaneous non-traumatic cases have been linked to anticoagulant therapy, pancreatitis, malignancy, vasculitis and endoscopy. We report an unusual case of spontaneous intramural duodenal hematoma presenting as an intestinal obstruction associated with acute pancreatitis in a patient with established von Willebrand disease, type 2B. The patient presented with abrupt onset of abdominal pain, nausea, and vomiting. Computed tomography imaging identified an intramural duodenal mass consistent with blood measuring 4.7 cm * 8.7 cm in the second portion of the duodenum abutting on the head of the pancreas. Serum lipase was 3828 units/L. Patient was managed conservatively with bowel rest, continuous nasogastric decompression, total parenteral nutrition, recombinant factor VIII (humateP) and transfusion. Symptoms resolved over the course of the hospitalization. This case highlights an important complication of an inherited coagulopathy. PMID- 24222966 TI - Magnetic endoscopic imaging vs standard colonoscopy: meta-analysis of randomized controlled trials. AB - AIM: To assess the theoretical advantages of magnetic endoscope imaging (MEI) over standard colonoscopies (SCs) and to compare their efficacies. METHODS: Electronic databases, including PubMed, EMBASE, the Cochrane library and the Science Citation Index, were searched to retrieve relevant trials. In addition, abstracts from papers presented at professional meetings and the reference lists of retrieved articles were reviewed to identify additional studies. The meta analyses were performed using RevMan 5.1. A random effect model with the Mantel Haenszel method was used for pooling dichotomous and continuous data. A sensitivity analysis was performed by excluding the trials with a small number of patients and by excluding the trials performed by inexperienced providers. RESULTS: Eight randomized controlled trials (RCTs), including 2967 patients, were included in the meta-analysis to compare cecal intubation rates and times, sedation dose, abdominal pain scores and the use of ancillary maneuvers between MEI and SC. The overall OR was 1.92 (95%CI: 1.13-3.27, eight RCTs), as indicated by the cecal intubation rate of MEI compared with SC, but MEI did not have any distinct advantage over SC for cecal intubation time (MD = -0.07, 95%CI: -0.16 0.02; three RCTs). MEI did not generally result in lower pain scores. Outcomes were also analyzed for the two subgroups based on the endoscopists' experience level to evaluate cecal intubation rates. MEI presented better outcomes for non experienced colonoscopists than experienced colonoscopists. CONCLUSION: The real time magnetic imaging system is of benefit in training and educating inexperienced endoscopists and improves the cecal intubation rate for experienced and inexperienced endoscopists. PMID- 24222968 TI - Endoscopic treatment of efferent loop syndrome with insertion of double pigtail stent. AB - Efferent loop syndrome is a very rare postgastrectomy syndrome that can occur following Billroth-II or Roux-en-Y reconstruction. The most common loop syndrome after gastric surgery is afferent loop syndrome; however, efferent loop syndrome has been reported in rare cases. Here, we report a case of efferent loop obstruction that occurred after postoperative adhesiolysis of a small-bowel obstruction. The patient had undergone a partial gastrectomy with Billroth II anastomosis and gastric ulcer perforation 30 years prior. The efferent loop obstruction was successfully resolved by the insertion of a double pigtail stent. To the best of our knowledge, this is the first case in the literature describing the treatment of efferent loop obstruction. PMID- 24222969 TI - Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease. AB - The concept of fecal microbiota transplantation (FMT) has been used in traditional Chinese medicine at least since the 4(th) century. Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease. We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease. However, there were no reports of FMT used in patients with severe Crohn's disease (CD). Here, we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula, residual Barium sulfate and formation of intraperitoneal large inflammatory mass. As far as we know, this is the first case of severe CD treated using FMT through mid-gut. PMID- 24222970 TI - Efficacy, effectiveness, immunogenicity--are not the same in vaccinology. AB - Manuscript of Carrera et al is devoted to immunization in inflammatory bowel disease (IBD) that is very important issue in gastroenterology. However, some specific definitions used in the article need clarification. Efficacy of vaccine is measured in a randomised, placebo-controlled studies, that are expensive and difficult to plan. Moreover, it is unethical to offer a placebo instead of vaccine. For all of these reasons, efficacy of vaccine is measured in IBD patients rarely. Effectiveness of vaccine is measured as an epidemiological affect from observational studies. These studies are also uncommon in IBD because it would be difficult to perform a study that assess the prevalence of one rare disease (vaccine-preventable) in patients with a chronic rare condition, such as IBD. Immunogenicity of vaccine refers to the ability of a vaccine to induce an immune response in a vaccinated individual that is, in fact, the matter of the article. PMID- 24222971 TI - Adolescent Friendships, BMI, and Physical Activity: Untangling Selection and Influence Through Longitudinal Social Network Analysis. AB - Bioecological theory suggests that adolescents' health is a result of selection and socialization processes occurring between adolescents and their microsettings. This study examines the association between adolescents' friends and health using a social network model and data from the National Longitudinal Study of Adolescent Health (N = 1,896, mean age = 15.97 years). Results indicated evidence of friend influence on BMI and physical activity. Friendships were more likely among adolescents who engaged in greater physical activity and who were similar to one another in BMI and physical activity. These effects emerged after controlling for alternative friend selection factors, such as endogenous social network processes and propinquity through courses and activities. Some selection effects were moderated by gender, popularity, and reciprocity. PMID- 24222972 TI - Shared metered dose inhalers among multiple patients: can cross-contamination be avoided? AB - Sharing metered dose inhalers among patients can lead to cross-contamination. PMID- 24222973 TI - Compounding Pharmacy Reform Moves Forward: Senate Bill's Exemption of Hospital Pharmacies Stirs Debate. AB - A Senate bill that exempts hospital compounding pharmacies from some rules is stirring debate. PMID- 24222975 TI - Pharmaceutical approval update. AB - Canagliflozin (Invokana) for type-2 diabetes; denosumab (Xgeva) for giant-cell tumor of bone; and paroxetine mesylate (Brisdelle) for vasomotor symptoms in menopause. PMID- 24222976 TI - Phentermine/Topiramate extended-release capsules (qsymia) for weight loss. AB - Phentermine/topiramate extended-release capsules (Qsymia) for weight loss. PMID- 24222977 TI - Diphenhydramine and acute kidney injury. AB - Seldom considered to be a drug that causes renal problems, diphenhydramine can have adverse effects in some patients, as illustrated by a case study of a middle aged veteran. Extra precautions are urged before this medication is prescribed, especially in elderly patients. PMID- 24222978 TI - Evaluating the appropriate use of piperacillin/tazobactam in a community health system: a retrospective chart review. AB - Noting inappropriate uses of piperacillin/tazobactam at their institution, the authors emphasize the need for antimicrobial stewardship efforts, as well as infection-control practices, to curtail drug resistance, reduce costs, and minimize adverse events. PMID- 24222979 TI - Transparency in evidence evaluation and formulary decision-making: from conceptual development to real-world implementation. AB - OBJECTIVE: Establishing a better understanding of the relationship between evidence evaluation and formulary decision-making has important implications for patients, payers, and providers. The goal of our study was to develop and test a structured approach to evidence evaluation to increase clarity, consistency, and transparency in formulary decision-making. STUDY DESIGN: The study comprised three phases. First, an expert panel identified key constructs to formulary decision-making and created an evidence-assessment tool. Second, with the use of a balanced incomplete block design, the tool was validated by a large group of decision-makers. Third, the tool was pilot-tested in a real-world P&T committee environment. METHODS: An expert panel identified key factors associated with formulary access by rating the level of access that they would give a drug in various hypothetical scenarios. These findings were used to formulate an evidence assessment tool that was externally validated by surveying a larger sample of decision-makers. Last, the tool was pilot-tested in a real-world environment where P&T committees used it to review new drugs. RESULTS: Survey responses indicated that a structured approach in the formulary decision-making process could yield greater clarity, consistency, and transparency in decision-making; however, pilot-testing of the structured tool in a real-world P&T committee environment highlighted some of the limitations of our structured approach. CONCLUSION: Although a structured approach to formulary decision-making is beneficial for patients, health care providers, and other stakeholders, this benefit was not realized in a real-world environment. A method to improve clarity, consistency, and transparency is still needed. PMID- 24222980 TI - Clinical outcomes after conversion from brand-name tacrolimus (prograf) to a generic formulation in renal transplant recipients: a retrospective cohort study. AB - After kidney transplant recipients who received Prograf were switched to generic tacrolimus, most differences in the safety and effectiveness of the medications were not considered clinically relevant. PMID- 24222981 TI - Evaluating a Learning Collaborative to Implement Evidence-Informed Engagement Strategies in Community-Based Services for Young Children. PMID- 24222982 TI - A Review of Intervention Programs to Prevent and Treat Behavioral Problems in Young Children with Developmental Disabilities. AB - Children with developmental disabilities are at higher risk for internalizing and externalizing behavioral problems than children in the general population. Effective prevention and treatment programs are necessary to reduce the burden of behavioral problems in this population. The current review identified 17 controlled trials of nine intervention programs for young children with developmental disabilities, with parent training the most common type of intervention in this population. Nearly all studies demonstrated medium to large intervention effects on child behavior post-intervention. Preliminary evidence suggests interventions developed for the general population can be effective for children with developmental disabilities and their families. A greater emphasis on the prevention of behavior problems in young children with developmental disabilities prior to the onset of significant symptoms or clinical disorders is needed. Multi-component interventions may be more efficacious for child behavior problems and yield greater benefits for parent and family adjustment. Recommendations for future research directions are provided. PMID- 24222984 TI - Congratulations dr walter peters, winner of the mentor prize. PMID- 24222983 TI - Comparison of commercial fibrin sealants in facelift surgery: a prospective study. AB - BACKGROUND: The aim of this study was to compare the effects of two types of fibrin glue in patients undergoing facelift surgery. METHODS: A prospective, controlled "right-left side" study was carried out in 20 patients. The two fibrin sealants used were Quixil(r) and Tissucol(r). The two sealants were used at the same time, ie, one on one side of the face and the other on the contralateral side. Comparisons were made with regard to rates of hematoma and seroma, degree of induration, edema, ecchymosis, pain levels, and patient satisfaction. RESULTS: The results were almost equivalent. The only exception was a significant (40 mL) hematoma in a patient treated with Quixil. Bleeding was most likely due to a sudden rise in blood pressure during the immediate postoperative period. However, it must be emphasized that, while Tissucol actually seals the undermined area, thus virtually eliminating the dead space, Quixil acts differently, in that its effectiveness in preventing hematoma is linked mainly to its hemostatic effect. CONCLUSION: The two fibrin sealants used were nearly identical with regard to patient safety and quality of the result. Nevertheless, it is noted that, while Tissucol has both hemostatic and "gluing" effects, Quixil is mainly effective in securing hemostasis. PMID- 24222985 TI - The medical information age. PMID- 24222986 TI - Recognition of potential morbidity after use of the radial artery as a conduit for coronary artery revascularization. AB - The use of the radial artery as an alternative vascular conduit for coronary bypass surgery has become increasingly popular. The plastic surgery experience with radial forearm flaps has shown that sacrifice of the radial artery is not always a benign maneuver. The potential morbidity after using this conduit donor site in terms of hand dysfunction or wound healing problems can be significant, and frequently must ultimately be addressed as part of the role of the reconstructive surgeon. Case examples of skin necrosis, subsequent forearm wound infection and hypertrophic scarring after radial artery harvest are presented to introduce this as a real concern and to allow a review of the entire spectrum of potential problems in this regard. Any selection process where the radial artery may be chosen as the coronary revascularization conduit must anticipate these known donor site complications. PMID- 24222987 TI - Sensitivity and specificity of clinical testing for carpal tunnel syndrome. AB - OBJECTIVE: The present study evaluated the sensitivity, specificity and predictive values of six clinical tests in the diagnosis of carpal tunnel syndrome (CTS). METHODS: There were 29 carpal tunnel syndrome (CTS) subjects (mean age 48 years) and 30 control subjects (mean age 45 years). The six clinical tests included Tinel's sign, wrist flexion with fingers extended, wrist flexion with fingers flexed, wrist extension, combined wrist extension/median nerve pressure and combined wrist flexion/median nerve pressure. RESULTS: The highest sensitivity and highest negative predictive value was found with wrist flexion with pressure (96%) and wrist extension with pressure (94%) at 60 s. The highest specificity was found with wrist flexion with fingers flexed for 30 s (95%). The highest positive predictive values were found with the wrist flexion with fingers flexed test for 30 s (91%) and the wrist extension test for 30 s (90%). CONCLUSION: No one test possesses all the qualities necessary to be the ideal clinical test for the detection of carpal tunnel syndrome. PMID- 24222988 TI - Simultaneous breast augmentation and mastopexy. AB - The results of combining breast augmentation and mastopexy are less predictable than those associated with mastopexy or augmentation mammoplasty alone. A method of breast skin envelope reduction is presented that allows the surgeon performing mastopexy to preview the final breast shape before committing to skin resection. This method, first described in 1978, has proven to be technically versatile and reproducible, and applicable not only to moderate (second degree) and severe (third degree) ptosis but also to simultaneous breast augmentation and mastopexy. For the combined procedures, the practical strategy proposed is first the implant placement through a periareolar incision, and a vertical transglandular incision, usually submusculofascial; second, restoring the gland anatomy by closing the muscularis and the vertical transglandular incision; third, skin envelope adjustment using the Tailor-Tack maneuver to accurately assure the best position of the nipple-areolar complex on the breast mound; fourth, skin incision, de epithelialization and undermining; and finally, closure combining the the Purse String maneuver with the vertical incision. PMID- 24222989 TI - Bilateral latissimus dorsi flaps for the reconstruction of extensive scalp defects. AB - BACKGROUND: The reconstruction of large scalp defects is occasionally required. Several methods of scalp reconstruction have previously been described. This paper presents the authors' experience with two patients in whom traditional methods were not sufficient and in whom bilateral latissimus dorsi free flaps were required. OBJECTIVES: To evaluate the effectiveness of a new technique in reconstructing extensive scalp defects. METHODS: Two case histories are presented. These include the rationale for the choice of reconstruction used as well as a discussion on the technical features of the surgery. RESULTS: Reconstruction was effective in both cases. However, one patient died in the early postoperative period from a pulmonary embolus. CONCLUSIONS: Bilateral latissimus flaps can be safely and effectively used in closing massive scalp defects in selected cases. PMID- 24222990 TI - Thoracoepigastric flap for the closure of an elbow defect in an intravenous drug abuser: A case report and review of literature. AB - The reconstruction of large soft tissue defects of the upper extremity is a challenging problem. Although free tissue transfer in a single stage is preferred, the recipient blood vessels usually determine the outcome. Due to venous occlusion from repeated intravenous drug abuse, the use of a thoracoepigastric flap to cover a complex wound of the elbow is reported. PMID- 24222991 TI - Subcutaneous basal cell carcinoma: A case report. AB - An unusual case of a patient who presented with a subcutaneous soft tissue lesion of the back is described. The patient had no preceding history of cutaneous malignancy or local trauma. Excision of the lesion revealed a diagnosis consistent with basal cell carcinoma with deep infiltration. The site was re excised with a generous margin to ensure complete removal. There has been no recurrence for 18 months. This case is presented to underscore the rarity and importance of its existence. PMID- 24222992 TI - Nonsurgical treatment of protruding ears: A case report and review of literature. AB - The nonsurgical correction of congenital ear deformities has been reported in the world literature. To date, there has been little interest in this procedure in pediatric centres and no reports in the Canadian literature. Two case reports are presented with a review of the literature. A description of this simple, user friendly office procedure is presented. PMID- 24222993 TI - Part IV: Reformers in medical education and practice: Effect of managed care organization in the United States. AB - BACKGROUND: Part I (Can J Plast Surg 2000;8:25-29) established that standards of professional practice shift constantly. When a standard falls short of professional expectation or when a physician becomes more concerned with financial gain rather than patient care, society needs the action of a reformer. Parts I, II (Can J Plast Surg 2001;9:59-68) and III (Can J Plast Surg 2002;10:103 108) covered 500 BC to 1970 AD and comprised 31 physicians who introduced innovations in medical knowledge or medical philosophy. Part IV deals with a time in which new conditions have been imposed on medical practice. In the United States, medical education and practice felt the repercussions of financial institutions participating in health care management. STUDY DESIGN: The reformers were scientists who conformed to our definition of 'reformer': a person whose action restored, reshaped or advanced the structure or ideology of medical practice. RESULTS: This survey demonstrated that the reforms were accomplished by scientists possessing critical judgement and analytical qualities that enabled them to influence the direction of medical education and practice. In the last 20 years, financial institutions imposed different criteria that may require future reformers to reestablish lost objectives. CONCLUSION: Reforms have been achieved through intuitive leaps, alterations of conventional practice, painstaking research or administrative restructuring. The present health management in the United States requires new solutions. PMID- 24222994 TI - Passing by on the other side. PMID- 24222995 TI - Can reduction mammoplasty patients be promised a particular size postoperatively? AB - This retrospective study used self-reported bra sizes, heights and weights pre- and postoperatively in patients who underwent reduction mammoplasty by one surgeon between 2001 and 2003. Preoperative data were collected on 91 patients. Postoperative data were collected from 69 respondents by telephone survey. Bra sizes were standardized according to cup size. In bra-making, the cup is the same size for decreasing cup letter size as the band size increases. The most common standardized cup size was seven, representing bra sizes 34 F, 36 E, 38 D, 40 C, etc. The range of preoperative cup sizes was five (34 D) to 17 (42 L). The mass of tissue removed from each breast was averaged for each patient and ranged from 147 g to 2453 g (mean 522 g). The average body mass index was 29.6 kg/m(2) preoperatively and 29.3 kg/m(2) postoperatively, with six patients reporting weight gain, 13 reporting weight loss and 50 reporting no change at all. Postoperative standardized cup sizes ranged from five (34 D) to 14 (44 H). The difference between pre- and postoperative cup size ranged from zero to eight as follows: for no cup size change (n=17), mean tissue removed per breast was 577.1 g; decrease by one cup size (n=23), 489.2 g; decrease by two cup sizes (n=25), 425.8 g. These data indicate that when self-reported data from patients are used, a plastic surgeon may find that as many as 25% report no change in bra size after reduction mammoplasty, even when more than 500 g of tissue is removed from each breast, which may adversely affect patients' satisfaction with the surgical results. Future studies will determine the cause of the apparent discrepancy between operative and self-reported results. PMID- 24222996 TI - Patterns of sensory and autonomic reinnervation of long-standing myocutaneous microvascular flaps and split-skin grafts applied to fascial beds. AB - BACKGROUND: There is a paucity of reports in the literature examining the pattern of sensory and autonomic neural recovery of myocutaneous microvascular flaps and skin grafts to the lower limbs after a prolonged period of time. OBJECTIVES: To investigate the recovery of sensation and autonomic nerve activity in long standing split-skin grafts applied to fascial beds and in myocutaneous microvascular flaps. METHODS: THE PATIENTS WERE DIVIDED INTO TWO GROUPS: group A consisted of patients with a split-skin graft applied to a fascial bed (n=11) and group B consisted of patients with free microvascular flaps (n=4). Patients in both groups underwent various clinical subjective and objective tests, including the measurement of electrical resistance and thermal sensory analysis. Laser Doppler flowmetry was used to investigate the blood flow patterns. RESULTS: Patients in both groups showed significantly reduced sensory modalities. However, the findings of both the electrical resistance and laser Doppler flowmetry were significantly different among the patients in group A compared with controls. In contrast, electrical resistance and laser Doppler flowmetry test results were similar in group B and controls. CONCLUSIONS: Both split-skin grafts applied to fascial beds and microvascular flaps on the lower limb had poor sensory recovery. However, after 15 years, the microvascular flaps regained the ability to sweat and some degree of thermoregulatory function. This may imply that the long standing myocutaneous free flaps regained some aspects of their autonomic innervation, whereas the split-skin grafts had not. PMID- 24222997 TI - Congenital arteriovenous malformations: A follow-up of treatment. AB - Due to the rarity of arteriovenous malformations (AVMs), there is a paucity of information on the outcomes of various treatments. Presently, the mainstays of treatment of an AVM are embolization, surgical excision or a combination of both. A retrospective study of 26 patients with AVMs treated at The Hospital for Sick Children, Toronto, Ontario between 1985 and 1995 was performed. The treatment strategies and patient outcomes were compared in terms of efficacy, complications and the response of patients and their families to their overall treatment. The overall findings showed that embolization alone was effective in controlling symptoms, but may be associated with an increased AVM size. A partial excision of an AVM does not appear to exacerbate recurrence, as has been previously reported. In fact, even after what appears to be a complete excision of the AVM, recurrence may still occur. Complications from a surgical excision of the AVM are more frequent but less devastating than complications from embolization of the lesion. The overall patient or parent satisfaction with treatment was high with respect to improvement in outcome. It is expected that with an increasing understanding of vascular malformations, and the evolution of interventional radiological techniques, complications will decrease and results as a whole will improve. PMID- 24222998 TI - Anomalous flexor digitorum superficialis muscle transposition for vascular coverage of the median nerve in recurrent carpal tunnel syndrome. AB - Recurrent carpal tunnel syndrome is uncommon yet troublesome. Significant adhesions and scarring around the median nerve can render it relatively ischemic. A number of vascular flaps have been described to provide vascular coverage in attempts to decrease further cicatricial adhesions and to improve local blood supply around the median nerve. A rare case of an anomalous muscle in the distal forearm used as tissue to provide good vascularized coverage of the median nerve that was severely scarred in its bed is reported. The anomalous muscle was distal to the flexor digitorum superficialis tendon and inserted in the palmar fascia on the ulnar aspect of the hand. Referring branches from the ulnar artery provided vascular supply to the anomalous muscle. The muscle on these vascular pedicles was transposed over the median nerve, providing good, stable, unscarred coverage. The patient had an excellent result with resolution of the carpal tunnel symptoms. The redundant anomalous muscle provided a unique vascularized source for coverage of the median nerve in recurrent carpal tunnel syndrome. PMID- 24222999 TI - Selecting optimal access for facial cyst removal: A case report and literature review. AB - Benign subcutaneous facial cysts are common in children and young adults. They are largely of cosmetic concern. Removal of sebaceous and epidermoid cysts in this population can leave unsightly scars, occasionally worse in appearance than the original pathology. In the present case report, the technique of cyst excision via an intaoral route is outlined. The literature review emphasizes the importance of placing facial incisions in inconspicuous areas. PMID- 24223000 TI - Case of hibernoma in the right supraclavicular fossa. AB - A patient with a supraclavicular mass originally diagnosed as a lipoma who was referred to a plastic surgeon for definitive treatment is presented. Gross intraoperative findings were inconsistent with lipoma, and subsequent pathological evaluation revealed the mass to be a hibernoma (a benign, brown adipose tumour). The incidence, etiology, presentation, pathology and imaging characteristics of this somewhat rare soft tissue tumour are reviewed. PMID- 24223001 TI - Masquerading Mycobacterium: Plastic surgeon to the rescue. AB - A patient with a Mycobacterium marinum infection of the hand is described. The present case illustrates that M marinum infection may mimic common skin conditions such as eczema, and fungal and parasitic infestations. Key elements in the diagnosis and management of this infection are a high index of suspicion, a detailed history of recreational or occupational exposure to exotic fish, tissue biopsy, wound culture and prompt empirical antibiotic therapy. Once in vitro organism sensitivities are obtained, antibiotic treatment may last for up to 24 months. Surgical drainage and debridement are an important supplement to antimicrobial therapy when subcutaneous structures are involved, as in the present report. Invasive digital and hand infections can rapidly result in permanent residual stiffness, deformity and loss of function; therefore, it is important to raise awareness of the condition among those considered to be at risk. PMID- 24223002 TI - Cutaneous ganglioneuroma within a giant congenital nevus. AB - Cutaneous ganglioneuroma has only occasionally been reported in the literature. Cutaneous ganglioneuroma is seen even more rarely in association with a giant congenital nevus. Differential diagnosis includes malignancies, especially melanoma and metastatic neuroblastoma. It is essential to rule out malignancy in a solid lesion within a congenital nevus. The present report is possibly the first relating ganglioneuroma and a congenital nevus to a cervical mass detected during routine prenatal ultrasound. PMID- 24223003 TI - A rare case of Pacinian corpuscle neuroma. AB - The authors discuss an interesting case of a Pacinian corpuscle neuroma in the thumb of an elderly woman who presented with severe digital pain. The pain was initially attributed to osteoarthritis of the interphalangeal joint of the thumb. The clinical signs were very subtle. The patient had complete pain relief following excision of the tumour. Pacinian corpuscle neuromas are rare, with only about 70 cases reported in the literature. The histology, presenting features and associated conditions are discussed in detail. In addition to a neuroma or glomus tumour, Pacinian corpuscle hyperplasia should be considered in the differential diagnosis of digital or palmar pain of unknown etiology. PMID- 24223004 TI - Acute ligation of the radial and ulnar arteries: A case report and review of literature. AB - Isolated injury to the radial or ulnar artery results in no significant complications in patients who undergo repair or ligation of the injured artery. However, ligation of both infrabrachial vessels of the upper extremity is associated with limb loss from ischemia due to lack of collateral circulation. A rare case of acute ligation of both the radial and ulnar arteries in a drug abuser where collateral vessels preserved the circulation to the hand is reported. PMID- 24223005 TI - Closure of a pharyngocutaneous fistula using a sternomastoid muscle flap. AB - Presented here is a case of a pharyngocutaneous fistula which was closed primarily using a sternomastoid muscle flap, without skin coverage, thus obviating the need for a three-layered closure. Providing an intermediate cover was sufficient for the closure because the mucosal lining on the inside and the cutaneous covering on the outside grew using the muscle for support. PMID- 24223006 TI - The suction-assisted curettage procedure. AB - Surgical soft tissue debridement of an inflamed or necrotic wound can be a challenging, time-consuming exercise, often with disproportionate blood loss. Suction-assisted curettage is a safe, simple and effective technique for these common, frustrating problems. PMID- 24223007 TI - A survey of volunteer reconstructive surgery performed outside of Canada by Canadian plastic surgeons. AB - BACKGROUND: Members of the Canadian Society of Plastic Surgeons have been offering humanitarian services to countries outside of Canada since the 1960s. OBJECTIVE: To document the extent of voluntary reconstructive services performed by members of the Canadian Society of Plastic Surgeons. METHOD: A survey was sent to all members of the Canadian Society of Plastic Surgeons asking them to list the extent of their voluntary services. RESULTS: Over 80 Canadian Society of Plastic Surgeons members have performed voluntary reconstructive services with more than 40 organizations in over 60 countries. CONCLUSION: These voluntary services provide a significant benefit to patients around the world and are rewarding for the surgeons who perform them. PMID- 24223008 TI - Are Canadian plastic surgeons "shooting themselves in the foot?" A point of view. PMID- 24223009 TI - Primary unilateral and bilateral cleft lip and nose in an older population. AB - A one-stage procedure to reconstruct complete and incomplete unilateral/bilateral cleft lip and nose deformities is presented. Emphasis was made on closure of the lip muscles, correction of the nostril floor, correction of the alveolar cleft as well as reconstruction of the nose through an intranasal approach, with a supported suture technique for nasal correction. No dental or orthodontic treatment was available or performed in this older population. Emphasis was on primary closure of the muscles, using the rotation advancement principle. The repair that was performed was near anatomical, reconstructing the labial sulcus, the nostril floor, the alveolar cleft and the nasal deformity all in one stage. There was a high level of satisfaction both from the patient's and surgeon's point of view. PMID- 24223010 TI - Alternative techniques for pedicle transfer of an island flap and a free flap. AB - Alternative techniques for pedicle transfer of a reverse radial forearm flap for hand coverage, and a latissimus dorsi myocutaneous free flap for pelvic wound coverage, are illustrated. Exteriorization of the vascular pedicle of a reverse radial forearm flap allows a greater arc of movement of the flap for more distal coverage, and avoids the potential vascular compromise of tunnelling under a tight skin bridge. Two-stage transfer of a latissimus dorsi myocutaneous free flap on a wrist carrier pedicle may be useful in circumstances when local recipient vessels are inadequate for free flap transfer. Although both of these vascular pedicle modifications have drawbacks, they may be of value in limited circumstances. Their advantages and limitations are discussed. PMID- 24223012 TI - Looking back to look forward. PMID- 24223011 TI - Use of the Mayfield horseshoe headrest for management of burns of the neck. AB - Proper positioning of a patient facilitates access and decreases frustration during surgical debridement of circumferential burns of the neck. The Mayfield swivel horseshoe headrest (Integra, USA) provides cranial support in either the supine or prone position for excision and skin grafting of the circumferential burns of the neck. This headrest can also be used during reconstruction of the neck. PMID- 24223013 TI - Patterns of reinnervation and blood flow in split-skin grafts. AB - One of the most important functions of skin is thermoregulation. The alterations in the patterns of blood flow in skin is one of the main physiological processes responsible for thermoregulatory control. The mechanisms governing the thermoregulatory control of cutaneous blood flow are mainly neural and chemical in nature. At present, there is a lack of studies in the literature looking at the relationship between reinnervation and the blood flow pattern of skin grafts. The present study uses Laser Doppler flowmetry and the immunohistochemical stains protein gene product 9.5, calcitonin gene-related peptide and substance P to identify nerve fibres, and antibodies to CD31 and von Willebrand factor to identify endothelial tissues. The aim of the present study was to investigate the patterns of blood flow and nerve tissue regeneration in split-skin grafts up to 15 years following the original procedure. Thirty-two split-skin grafts were studied and these were placed into two groups based on the nature of the bed of excision: group I consisted of patients who underwent tangential excision and split-skin grafting (n=17), and group II consisted of patients with split-skin grafts placed onto fascial beds (n=15). Each subpopulation of patients was further divided into three groups based on the length of time following grafting: one to three years, four to six years and seven to 15 years. These divisions were arbitrarily chosen and called A1, A2 and A3, respectively. In the Laser Doppler flowmetry arm of the study, the grafts were assessed at various stages after heating, cooling and further reheating. The Laser Doppler flowmetry studies showed that, on subjecting the skin grafts in both groups I and II to heating and cooling followed by reheating, the overall response of the blood flow to changes in the temperature was slower. The immunohistochemical analysis showed that in all graft types and graft ages, protein gene product 9.5, calcitonin gene-related peptide and substance P stains demonstrated a relative lack of the presence of nerve fibres in the split-skin grafts compared with the control ('normal' skin). However, von Willebrand factor and CD31 immunological staining demonstrated that vessels were present in the split-skin grafts, with no significant difference in size or quantity from the control samples. It was found that the blood flow in the split-skin graft in response to thermal challenge, although present, was slower than that of normal skin, a finding which was independent of the age of the skin graft. It is thought that this was related to a lack of regeneration of nerve fibres and, hence, a deficiency in the neurally mediated reflexes of the blood vessels within the split-skin grafts. PMID- 24223014 TI - Narrowing of the wide nasal dorsum in the 'minimal-hump' nose: A simplified universal approach. AB - The operative procedure frequently used to narrow the nasal pyramid in the context of a regular rhinoplasty is well known to all rhinoplastic surgeons. It consists of hump removal, followed by lateral osteotomies and medialization of the nasal bones. However, narrowing of a wide nasal pyramid, in the absence of an appreciable dorsal hump, as in the case of an ideal dorsal height or a mild hump, presents a different challenge. The present article describes a simplified approach to the 'nasal plateau resection', a technique that allows the creation of an open nasal roof, without hump removal and without compromising dorsal projection. This permits the medialization of the lateral nasal bones and the subsequent narrowing of the wide pyramid, while preserving the height of the nasal dorsum as viewed in profile. PMID- 24223015 TI - Solo hand surgery. AB - Unassisted hand surgery is being undertaken by necessity for both elective and emergency cases, due to hospital resource restrictions. The authors outline the principles of local anesthesia, surgeon-controlled tourniquet techniques, and a number of new instruments which allow a surgeon to work in comfort and safety, unassisted. The traditional surgical instruments designed for the days when trained surgical assistants were available to hold them are no longer suitable. We are entering a new era of surgical design with safer instruments that can complement our skills rather than challenge them. There are significant cost savings and efficiency when hand procedures are undertaken in the emergency and outpatient clinic settings. PMID- 24223016 TI - Nasal dorsum skin expansion for reconstruction of saddle nose due to gunshot injury: A case report. AB - Saddle nose deformity due to gunshot injury is a challenging problem for the maxillofacial surgeon. Because of the severe damage to the soft and bony tissues, the reconstructive options are very limited. In the present case report, a saddle nose deformity sustained from gunshot injury was reconstructed with a porous polyethylene nasal implant after a successful expansion of the nasal dorsum skin. Healing was uneventful at two-year follow-up, with superior patient satisfaction. Nasal dorsum skin expansion should be considered as an option in the reconstruction of moderately sized soft tissue deficits of the nose. PMID- 24223017 TI - Traumatic intratendinous flexor digitorum profundus rupture: A case report. AB - Intratendinous ruptures of a flexor digitorum profundus tendon are rare in patients who do not have rheumatoid arthritis. A case of a patient with no history of autoimmune disease who suffered a traumatic rupture of the flexor digitorum profundus tendon to the ring finger in the mid-palm is reported. PMID- 24223018 TI - Groin flap for salvage of upper extremity following necrotizing fasciitis: A case report. AB - Necrotizing soft tissue infections are often associated with significant morbidity and mortality. Early surgical excision along with antibiotic therapy is the cornerstone of management. Salvage of these extremities is often difficult due to loss of soft tissues, tendons, nerves and blood vessels. Skin grafting of the granulating wound is the common method of closure in these patients. Use of various flaps has improved reconstructive options in these extremities. A case of salvage of upper extremity using a groin flap following extensive debridement is reported. PMID- 24223019 TI - A nu-space for ICS: characterization and application to measure protein transport in live cells. AB - We introduce a new generalized theoretical framework for image correlation spectroscopy (ICS). Using this framework, we extend the ICS method in time frequency (nu, nu) space to map molecular flow of fluorescently tagged proteins in individual living cells. Even in the presence of a dominant immobile population of fluorescent molecules, nu-space ICS (nICS) provides an unbiased velocity measurement, as well as the diffusion coefficient of the flow, without requiring filtering. We also develop and characterize a tunable frequency-filter for STICS that allows quantification of the density, the diffusion coefficient and the velocity of biased diffusion. We show that the techniques are accurate over a wide range of parameter space in computer simulation. We then characterize the retrograde flow of adhesion proteins (alpha6- and alphaLbeta2-GFP integrins and mCherry-paxillin) in CHO.B2 cells plated on laminin and ICAM ligands respectively. STICS with a tunable frequency filter, in conjunction with nICS, measures two new transport parameters, the density and transport bias coefficient (a measure of the diffusive character of a flow/biased diffusion), showing that molecular flow in this cell system has a significant diffusive component. Our results suggest that the integrinligand interaction, along with the internal myosin-motor generated force, varies for different integrin-ligand pairs, consistent with previous results. PMID- 24223020 TI - Use of herbal supplements for overactive bladder. AB - Anticholinergics, specifically antimuscarinic agents, are the most common medications prescribed for overactive bladder (OAB). The most common side effects of these agents are dry mouth and constipation, although other more concerning effects include changes in blood pressure, pulse rate, or heart rhythm when treatment is initiated. Herbal treatments are an increasingly popular alternative for treating OAB. A 2002 survey of US adults aged >= 18 years conducted by the Centers for Disease Control and Prevention indicated that 74.6% of those with OAB had used some form of complementary and alternative medicine. The World Health Organization estimates that 80% of the world's population presently uses herbal medicine for some aspect of primary health care. Women were more likely than men to use complementary and alternative medicine. The authors review the most commonly used herbal medications for OAB. PMID- 24223021 TI - Prostate-specific antigen: any successor in sight? AB - Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer death in men in the United States and other parts of the world. The lifetime risk of being diagnosed with PCa is approximately 16%. At present, the only widely accepted screening tools for PCa are prostate-specific antigen (PSA) and digital rectal examination. PSA is known to be prostate specific, but not PCa specific, and hence lacks the sensitivity to detect a large number of tumors, especially during the early stages. The PSA level is also known to be affected by many factors, such as medication, inflammation (benign prostatic hyperplasia and prostatitis), and urologic manipulation; hence, the controversy regarding the appropriate level of serum PSA that should trigger a biopsy or have clinical relevance to prostate metastases. Attempts to determine the level of prostate cells in peripheral blood by reverse transcriptase polymerase chain reaction did not significantly improve cancer diagnosis or predict postoperative failure. Therefore, the search continues for a novel biomarker or a panel of markers as well as other possible interventions to improve the use of PSA. This article reviews several possibilities. PMID- 24223022 TI - Bladder cancer after radiotherapy for prostate cancer. AB - External beam radiotherapy (EBRT) is frequently used in the management of prostate cancer (PCa) as definitive, postoperative, or salvage local treatment. Although EBRT plays a central role in the management of PCa, complications remain a troubling by-product. Several studies have demonstrated an association between radiotherapy and elevated risk of acute and late toxicities. A secondary malignancy induced by initial therapy represents one of the most serious complications related to definitive cancer treatment. The radiation-related secondary primary malignancy risk increases with increasing survival time. Transitional cell carcinoma of the bladder is the most frequent secondary primary malignancy occurring after radiotherapy and is described as more aggressive; it may be diagnosed later because some radiation oncologists believe that the hematuria that occurs after prostate EBRT is normal. Some patients treated for localized PCa will subsequently develop invasive bladder cancer requiring surgical intervention. Patients with PCa treated with EBRT should be monitored closely for the presence of bladder cancer. PMID- 24223023 TI - The case for hypofractionation of localized prostate cancer. AB - An optimal treatment regimen for localized prostate cancer (PCa) is yet to be determined. Increasing evidence reveals a lower alpha/beta ratio for PCa with hypofractionated radiation therapy (HFRT) regimens introduced to exploit this change in therapeutic ratio. HFRT also results in shortened overall treatment times of 4 to 5 weeks, thus reducing staffing and machine burden, and, more importantly, patient stress. This review evaluates pretreatment characteristics, outcomes, and toxicity for 15 HFRT studies on localized PCa. HFRT results in comparable or better biochemical relapse-free survival and toxicity and is a viable option for localized PCa. PMID- 24223024 TI - Best of the 2013 AUA Annual Meeting Part II: More Highlights From the 2013 American Urological Association Annual Meeting, May 4-8, 2013, San Diego, CA. PMID- 24223025 TI - Ureteral metastasis as the presenting manifestation of pancreatic carcinoma. AB - We recently cared for a patient with adenocarcinoma of the pancreas who presented with ureteral metastasis followed by hydroureteronephrosis long before the appearance of any symptoms related to the primary lesion. The entity is extremely rare; only seven similar cases are on record in the scientific literature. No recent review exists on this topic. This encouraged us to present our case along with the previous cases of adenocarcinoma of the pancreas with ureteral metastasis that have been reported. PMID- 24223026 TI - Obstructed bifid uretereric system causing unilateral hydronephrosis. AB - Bifid ureters are a common malformation of the urinary system. In clinical practice, hydronephrosis resulting from obstruction of such a system is rare. The authors present a case involving an 88-year-old man admitted to the hospital with symptoms of renal failure, where bifid ureters were found incidentally in a hydronephrotic kidney during an emergency nephrostomy. This had been missed on a previous CT scan, resulting in a unique therapeutic dilemma. PMID- 24223027 TI - L'eggo My Ego: Reducing the Gender Gap in Math by Unlinking the Self from Performance. AB - Stereotype threat can vary in source, with targets being threatened at the individual and/or group level. This study examines specifically the role of self reputational threat in women's underperformance in mathematics. A pilot study shows that women report concerns about experiencing self-reputational threat that are distinct from group threat in the domain of mathematics. In the main study, we manipulated whether performance was linked to the self by asking both men and women to complete a math test using either their real name or a fictitious name. Women who used a fictitious name, and thus had their self unlinked from the math test, showed significantly higher math performance and reported less self-threat and distraction, relative to those who used their real names. Men were unaffected by the manipulation. These findings suggest that women's impaired math performance is often due to the threat of confirming a negative stereotype as being true of the self. The implications for understanding the different types of threats faced by stereotyped groups, particularly among women in math settings, are discussed. PMID- 24223028 TI - An accelerated proximal gradient algorithm for singly linearly constrained quadratic programs with box constraints. AB - Recently, the existed proximal gradient algorithms had been used to solve non smooth convex optimization problems. As a special nonsmooth convex problem, the singly linearly constrained quadratic programs with box constraints appear in a wide range of applications. Hence, we propose an accelerated proximal gradient algorithm for singly linearly constrained quadratic programs with box constraints. At each iteration, the subproblem whose Hessian matrix is diagonal and positive definite is an easy model which can be solved efficiently via searching a root of a piecewise linear function. It is proved that the new algorithm can terminate at an epsilon-optimal solution within [Formula: see text] iterations. Moreover, no line search is needed in this algorithm, and the global convergence can be proved under mild conditions. Numerical results are reported for solving quadratic programs arising from the training of support vector machines, which show that the new algorithm is efficient. PMID- 24223029 TI - Epsilon-Henig saddle points and duality of set-valued optimization problems in real linear spaces. AB - We study Epsilon-Henig saddle points and duality of set-valued optimization problems in the setting of real linear spaces. Firstly, an equivalent characterization of Epsilon-Henig saddle point of the Lagrangian set-valued map is obtained. Secondly, under the assumption of the generalized cone subconvexlikeness of set-valued maps, the relationship between the Epsilon-Henig saddle point of the Lagrangian set-valued map and the Epsilon-Henig properly efficient element of the set-valued optimization problem is presented. Finally, some duality theorems are given. PMID- 24223030 TI - Microscale investigation of arsenic distribution and species in cement product from cement kiln coprocessing wastes. AB - To improve the understanding of the immobilization mechanism and the leaching risk of Arsenic (As) in the cement product from coprocessing wastes using cement kiln, distribution and species of As in cement product were determined by microscale investigation methods, including electron probe microanalysis (EPMA) and X-ray absorption spectroscopy. In this study, sodium arsenate crystals (Na3AsO412H2O) were mixed with cement production raw materials and calcined to produce cement clinker. Then, clinker was mixed water to prepare cement paste. EPMA results showed that As was generally distributed throughout the cement paste. As content in calcium silicate hydrates gel (C-S-H) was in low level, but higher than that in other cement mineral phases. This means that most of As is expected to form some compounds that disperse on the surfaces of cement mineral phases. Linear combination fitting (LCF) of the X-ray absorption near edge structure spectra revealed that As in the cement paste was predominantly As(V) and mainly existed as Mg3(AsO4)2, Ca3(AsO4)2, and Na2HAsO4. PMID- 24223031 TI - Particle formation by supercritical fluid extraction and expansion process. AB - Supercritical fluid extraction and expansion (SFEE) patented technology combines the advantages of both supercritical fluid extraction (SFE) and rapid expansion of supercritical solution (RESS) with on-line coupling, which makes the nanoparticle formation feasible directly from matrix such as Chinese herbal medicine. Supercritical fluid extraction is a green separation technology, which has been developed for decades and widely applied in traditional Chinese medicines or natural active components. In this paper, a SFEE patented instrument was firstly built up and controlled by LABVIEW work stations. Stearic acid was used to verify the SFEE process at optimized condition; via adjusting the preexpansion pressure and temperature one can get different sizes of particles. Furthermore, stearic acid was purified during the SFEE process with HPLC-ELSD detecting device; purity of stearic acid increased by 19%, and the device can purify stearic acid. PMID- 24223032 TI - Glutathione redox system in beta -thalassemia/Hb E patients. AB - beta -thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH)/glutathione disulfide (GSSG) and also to evaluate glutathione related responses to oxidation in beta -thalassemia/Hb E patients. Twenty-seven normal subjects and 25 beta -thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body's first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores. PMID- 24223033 TI - A blind reversible robust watermarking scheme for relational databases. AB - Protecting the ownership and controlling the copies of digital data have become very important issues in Internet-based applications. Reversible watermark technology allows the distortion-free recovery of relational databases after the embedded watermark data are detected or verified. In this paper, we propose a new, blind, reversible, robust watermarking scheme that can be used to provide proof of ownership for the owner of a relational database. In the proposed scheme, a reversible data-embedding algorithm, which is referred to as "histogram shifting of adjacent pixel difference" (APD), is used to obtain reversibility. The proposed scheme can detect successfully 100% of the embedded watermark data, even if as much as 80% of the watermarked relational database is altered. Our extensive analysis and experimental results show that the proposed scheme is robust against a variety of data attacks, for example, alteration attacks, deletion attacks, mix-match attacks, and sorting attacks. PMID- 24223034 TI - Comparison of nocturia response to desmopressin treatment between patients with normal and high nocturnal bladder capacity index. AB - OBJECTIVE: To compare efficacy of desmopressin for treatment of nocturia between patients with normal and high nocturnal bladder capacity index (NBCi). METHODS: Retrospective analysis of adult patients treated with desmopressin for nocturia. Patients were analyzed according to high or normal NBCi value before treatment. RESULTS: 55 patients were identified, aged 49-84, 47 males, 8 females, who started desmopressin 0.2 mg nocte between 2009 and 2011. Two groups (N: normal and H: high NBCi) were similar regarding number, gender, age, 24 h urine volume, and nocturnal urine volume. On treatment, nocturnal volume decreased by mean of 364 mL. Number of nightly voids decreased in N group from 3.11 to 1.50, in H from 3.96 to 1.44. Nocturnal polyuria and nocturia indices also decreased significantly. NBCi remained the same in N group (0.56 on therapy) and in H group decreased to mean 0.63. All on-treatment values were statistically similar in N and H groups. Pretreatment differences were abolished with treatment. NBCi was significantly correlated to nocturia reduction-larger reduction was observed in patients with higher NBCi. In 8/55 patients, hyponatremia was detected, but without clinical consequences. CONCLUSIONS: The results indicate that the effectiveness of desmopressin on nocturia is not dependent upon the patient's pretreatment NBCi. PMID- 24223035 TI - Postmarket surveillance of medical devices: a comparison of strategies in the US, EU, Japan, and China. PMID- 24223036 TI - Impact of Physical Health on Treatment for Co-occurring Depression and Substance Dependence. AB - OBJECTIVE: There is a high rate of comorbidity among substance dependence, depression, and physical health problems. This study aimed to examine the impact of pre-treatment physical health stressors (acute and chronic conditions) on outcomes of treatment in a sample of veterans with dual disorders (depression and substance dependence) who were randomized to integrated cognitive behavioral therapy versus 12-Step interventions. METHODS: This study included 205 veterans (89.8% male, mean age = 49.5 years) enrolled in a clinical treatment outcomes trial. Chronic health problems (persistent, ongoing conditions lasting 2 weeks or more; e.g., arthritis, diabetes) and acute health events (occurring on a discrete date; e.g., injury, surgery, myocardial infarction) were coded dichotomously (presence versus absence) and evaluated separately. The impact of physical health stressors on abstinence (defined dichotomously), percentage of days abstinent, and depression symptoms were analyzed at the end of 12 and 24 weeks of treatment. Additionally, associations between intake motivation to change, health stressors, and substance use were examined. RESULTS: Analyses revealed that participants who had experienced a pretreatment acute health event had higher rates of abstinence at 12-weeks, higher percentage of days abstinent at 24-weeks, and higher depression symptoms at intake. Participants with chronic health difficulties had more severe depression at intake and those participants with severe chronic difficulties had greater depression symptoms across all time points. Chronic health difficulties were related to the Taking Steps factor of motivation to change substance use, but acute health events were not related to motivation to change. Motivation to change was also not related to substance outcomes in our sample. CONCLUSIONS: Physical health appears to have a complex relationship with co-occurring depression and substance dependence. Acute health problems predicted lower substance use, whereas chronic health problems were associated with higher depression levels. Explicitly addressing the connection between substance use and health events during treatment may improve addiction treatment outcomes. However, individuals with chronic health problems may benefit from extending treatment or adjunct strategies focused on addressing chronic health concerns. This is an analysis of data collected as part of a clinical trial registered at www.ClinicalTrials.gov as NCT00108407. PMID- 24223037 TI - Skin Cancer Knowledge, Beliefs, Self-Efficacy, and Preventative Behaviors among North Mississippi Landscapers. AB - There are slightly over one million workers in the landscape service industry in the US. These workers have potential for high levels of solar ultraviolet radiation exposure, increasing their risk of skin cancer. A cross-sectional sample of 109 landscapers completed a self-administered questionnaire based on Health Belief Model (HBM). The participants correctly answered 67.1% of the knowledge questions, 69.7% believed they were more likely than the average person to get skin cancer, and 87.2% perceived skin cancer as a severe disease. Participants believed that the use of wide-brimmed hats, long sleeved shirts/long pants, and sunscreen was beneficial but reported low usage of these and other sun protective strategies. The primary barriers to using sun protection were "I forget to wear it" and "it is too hot to wear." Of the HBM variables, perceived benefits outweighing perceived barrier (r = .285, P = .003) and self-efficacy (r = .538, P = .001) were correlated with sun protection behaviors. The reasons for absence of the relationship between perceived skin cancer threat and sun protection behaviors could be lack of skin cancer knowledge and low rate of personal skin cancer history. PMID- 24223038 TI - Osteoporosis. PMID- 24223039 TI - Antimicrobial Activities of Leaf Extracts of Guava (Psidium guajava L.) on Two Gram-Negative and Gram-Positive Bacteria. AB - Aim. To determine the antimicrobial potential of guava (Psidium guajava) leaf extracts against two gram-negative bacteria (Escherichia coli and Salmonella enteritidis) and two gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) which are some of foodborne and spoilage bacteria. The guava leaves were extracted in four different solvents of increasing polarities (hexane, methanol, ethanol, and water). The efficacy of these extracts was tested against those bacteria through a well-diffusion method employing 50 MU L leaf-extract solution per well. According to the findings of the antibacterial assay, the methanol and ethanol extracts of the guava leaves showed inhibitory activity against gram positive bacteria, whereas the gram-negative bacteria were resistant to all the solvent extracts. The methanol extract had an antibacterial activity with mean zones of inhibition of 8.27 and 12.3 mm, and the ethanol extract had a mean zone of inhibition of 6.11 and 11.0 mm against B. cereus and S. aureus, respectively. On the basis of the present finding, guava leaf-extract might be a good candidate in the search for a natural antimicrobial agent. This study provides scientific understanding to further determine the antimicrobial values and investigate other pharmacological properties. PMID- 24223040 TI - Long-term effect of enzyme replacement therapy with fabry disease. AB - Objective. To determine the effects of enzyme replacement therapy (ERT) on the hearing acuity in patients with Fabry disease. Materials. The study sample comprised 34 ears of 17 affected patients who underwent pure-tone audiometry before and after ERT. Methods. The patients were studied in relation to factors such as changes in hearing, presence of accompanying symptoms, status of renal and cardiac function, age, and gender. Data of pure-tone audiometry obtained before ERT and at the final examination were compared. Results. At the end of the follow-up period, no significant worsening of hearing acuity was noted at the end of the follow-up period. SSNHL was detected in 10 ears of 6 patients. Steroid therapy successfully cured the disease in 9 of the 10 ears. Conclusions. No significant worsening of hearing acuity was noted from the beginning to the end of ERT. The rate of improvement in SSNHL of Fabry disease was excellent in the treated patients. Hearing loss is a factor that causes marked deterioration of the patients' quality of life, and it is desirable that the hearing acuity of patients be periodically evaluated and prompt treatment of SSNHL be administered, if available. PMID- 24223041 TI - Providers' perceptions of challenges in obstetrical care for somali women. AB - Background. This pilot study explored health care providers' perceptions of barriers to providing health care services to Somali refugee women. The specific aim was to obtain information about providers' experiences, training, practices and attitudes surrounding the prenatal care, delivery, and management of women with Female Genital Cutting (FGC). Methods. Individual semi-structured interviews were conducted with 14 obstetricians/gynecologists and nurse midwives in Columbus, Ohio. Results. While providers did not perceive FGC as a significant barrier in itself, they noted considerable challenges in communicating with their Somali patients and the lack of formal training or protocols guiding the management of circumcised women. Providers expressed frustration with what they perceived as Somali patients' resistance to obstetrical interventions and disappointment with a perception of mistrust from patients and their families. Conclusion. Improving the clinical encounter for both patients and providers entails establishing effective dialogue, enhancing clinical and cultural training of providers, improving health literacy, and developing trust through community engagement. PMID- 24223043 TI - Standing on the Shoulders of our Editors Emeriti. PMID- 24223042 TI - The estrogen receptor joins other cancer biomarkers as a predictor of outcome. AB - Endometrial cancer, the most common gynecologic malignancy in the United States, is on the rise, and survival is worse today than 40 years ago. In order to improve the outcomes, better biomarkers that direct the choice of therapy are urgently needed. In this review, we explore the estrogen receptor as the most studied biomarker and the best predictor for response for endometrial cancer reported to date. PMID- 24223044 TI - Choosing child and adolescent psychiatry: factors influencing medical students. AB - OBJECTIVE: To examine the factors influencing medical students to choose child and adolescent psychiatry as a career specialty. METHOD: Quantitative and qualitative methods were used. A web-based survey was distributed to child and adolescent psychiatrists at the University of Toronto. In-depth interviews were held with select child and adolescent psychiatrists as well as a focus group with psychiatry residents. Retrospective accounts of the factors that influenced their decision to choose psychiatry and/or child and adolescent psychiatry as a specialty were collected. RESULTS: Ninety-two percent of participants indicated that recruitment of child psychiatrists in Canada is a problem. The recent decision by the Royal College of Physicians and Surgeons to recognize child and adolescent psychiatry as a subspecialty and introduce an extra year of training was identified as a further challenge to recruitment efforts. Other deterrents included lower salary than other subspecialties, lack of exposure during training, stigma, and lack of interest in treating children. Recruitment into psychiatry was enhanced by good role modeling, early exposure in medical school, an interest in brain research, and career and lifestyle issues. CONCLUSIONS: A rebranding of the role and perception of psychiatry is needed to attract future psychiatrists. Early exposure to innovations in child and adolescent psychiatry and positive role models are critical in attracting medical students. Recruitment should begin in the first year of medical school and include an enriched paediatric curriculum. PMID- 24223045 TI - Integrated Knowledge Translation and Grant Development: Addressing the Research Practice Gap through Stakeholder-informed Research. AB - OBJECTIVE: We describe our stakeholder engagement process for grant application development that occurred as part of our integrated knowledge translation plan and make recommendations for researchers. METHOD: In phase 1, a stakeholder consultation group was developed. In phase 2, surveys regarding knowledge gathering, research agenda, and research collaboration preferences were sent to 333 cross-sectoral youth-serving organizations in Ontario, including family and consumer organizations. RESULTS: In phase 1, 28 stakeholders from six sectors participated in the consultation group and provided input on multiple aspects of the proposal. Through this process, 19 stakeholders adopted formal roles within the project. In phase 2, 206 surveys were received (response rate = 62%). Survey responses supported the grant focus (concurrent youth mental health and substance use problems). Respondents also prioritized project goals and provided specific feedback on research and knowledge translation. Finally, although some stakeholders chose greater involvement, most survey respondents indicated a preference for a moderate level of participation in research rather than full team membership. CONCLUSIONS: Despite short timelines and feasibility challenges, stakeholders can be meaningfully engaged in and contribute to the grant proposal development process. Consideration is needed for the practical challenges that stakeholder organizations face in supporting and participating in research. PMID- 24223046 TI - Helpseeking of immigrant and native born parents: a qualitative study from a montreal child day hospital. AB - OBJECTIVES: This qualitative study of the perceptions of native-born Canadian and immigrant parents whose children attended a psychiatric day hospital for significant behavior impairment, focused on parental helpseeking pathways, explanatory models of mental health, and referral or access experiences. METHODS: A sample of ten immigrant and ten native born parents were recruited for semi structured interviews analyzed thematically to discern similarities and differences between the two groups. RESULTS: The immigrant group more frequently reported barriers and delays in accessing mental health services. They often reported lack of primary care physicians and language barriers. They were less likely to have a biomedical perspective or to use specialized resources for their children prior to admission. Both groups reported apprehension about medication trials, though the immigrant parents were less likely to agree to psychopharmacological treatment. None of the professionals treating parents for mental health problems initiated referral of their impaired children. CONCLUSIONS: Based on the qualitative analysis of this sample, native born single parents and immigrant parents may feel especially vulnerable to lack of social support. Adjustments of primary care, schools and community resources, as well as promoting best practices of culturally competent child mental health care, may increase access and willingness to pursue treatment in both groups. PMID- 24223047 TI - Living from day to day - qualitative study on borderline personality disorder in adolescence. AB - OBJECTIVE: The purpose of this study was to assess how far identity and self image disturbances are features of borderline personality disorder (BPD) in adolescence. METHOD: Face-to-face interviews were carried out with a total of 50 adolescents with BPD and 50 controls, with a median age of 16 (SD 1.1; range 13 to 18) years. Data was analysed using a qualitative methodology, interpretative phenomenological analysis (IPA). Thematic statements representative of adolescents' lived experience were extracted from the interviews. RESULTS: Four main themes representing the day-to-day experiences of adolescents with BPD were identified: emotional experiences characterised by the feelings of fear, sadness and pessimism; interpersonal relationships characterised by the feelings of solitude and hostility from others; a conformist self-image characterised by a feeling of normality and difficulty in projecting into time; and, a structuring of discourse characterised by discontinuity in the perception of experiences. CONCLUSION: This qualitative study suggests that the day-to-day experiences of adolescents with borderline personality disorder is centred on the experience of the present. Discontinuity in self-image, alongside marked dysphoric manifestations, leads to distress and hinders compliance with care. These issues are highly relevant in psychotherapy and could lead to more effective treatment of the disorder in adolescents. PMID- 24223048 TI - Anxiety and Depression among Parents of Children with Intellectual Disability in Pakistan. AB - BACKGROUND: Studies have shown an association between parental distress and caretaking of children with developmental cognitive delays. There is little data in developing countries, such as Pakistan, concerning the impact of raising children with intellectual disability upon the quality of parent functioning and risk for psychopathology. OBJECTIVE: To assess the level of psychopathology i.e. anxiety, depression and both anxiety and depression together among parents of children with intellectual disability (ID). METHODS: This was a cross-sectional study conducted at a tertiary care hospital in Pakistan. The study was approved by the Institutional Research Committee. Participants were 198 parents (99 fathers/99 mothers) of 100 children with the diagnosis of ID. Informed consents were obtained. The parents were assessed for anxiety and depression using DSM IV criteria. RESULTS: Significantly high proportion of mothers (89%) had anxiety, depression, or both anxiety and depression together as compared to fathers (77%) (p-value <0.05). Among mothers, 35% met criteria for anxiety, 40% for depression and 13% for both anxiety and depression. Among fathers 42% had anxiety, 31% depression and 3% both anxiety and depression. There was a significant association between gender of parent and individual psychiatric diagnosis of anxiety, depression and anxiety and depression together (p-value <0.05). A significant association was also found between mother's anxiety, depression or both and degree of ID of their children (p-value <0.05). CONCLUSIONS: 1) Significantly high proportion of parents of children with ID has psychiatric diagnosis of anxiety, depression or both; 2) the psychiatric diagnosis of anxiety, depression and anxiety and depression together is associated with gender of parent; and, 3) the diagnosis of anxiety, depression or both in mothers was associated with severity of ID in their children. PMID- 24223049 TI - Program evaluation of a child and youth mental health training program for family physicians in british columbia. AB - INTRODUCTION: This brief report presents findings from the program evaluation of a portion of an educational program developed to support family physicians in improving their mental health care competencies in children and youth in British Columbia. METHOD: The Child and Youth Mental Health (CYMH) learning module is part of a broader initiative from the Practice Support Program (PSP) of the British Columbia Medical Association and was created specifically to assist family physicians in improving their competencies in the identification, diagnosis and delivery of best evidence-based treatments for children and youth exhibiting the most common mental disorders that can be effectively treated in most primary care practices. RESULTS: The initial results from the program evaluation demonstrate a substantial improvement in family physicians' knowledge of child and youth mental disorders and their self-rated clinical confidence in identifying and treating (both pharmacologically and psychotherapeutically) the most common child and youth mental disorders. Furthermore, because the training protocol involves a team-based approach which includes specialist physicians as well as school counsellors and human services providers, collaboration between primary practice and other providers is enhanced. CONCLUSION: The initial results encourage broader roll-out and further evaluation of this program on a wider scale. PMID- 24223050 TI - Direct and Indirect Psychosocial Outcomes for Children with Autism Spectrum Disorder and their Parents Following a Parent-involved Social Skills Group Intervention. AB - OBJECTIVE: This study examined the direct and indirect outcomes of a social skills group intervention for children with high functioning autism spectrum disorders and their parents. METHOD: Thirty-five children and their parents participated in the program evaluation. Children and parents completed measures of child social skills and problem behaviors. Children reported on their self concept, and parents reported on their psychological acceptance and empowerment. RESULTS: Results indicate significant increases in overall child social skills according to parent and child report, in child general self-worth, and in parent service empowerment and psychological acceptance. CONCLUSION: While past program evaluations of social skills groups highlight changes in social competence, taking a broader perspective on the types of positive outcomes suggests potential benefits for both child and parent. PMID- 24223051 TI - The canadian eating disorder program survey - exploring intensive treatment programs for youth with eating disorders. AB - OBJECTIVE: To explore and describe philosophies and characteristics of intensive eating disorder (ED) treatment programs based in tertiary care institutions across Canada. METHOD: A ninety-item survey examining ED services for adolescents was developed, piloted, and completed by 11 programs across Canada. Information pertaining to program characteristics and components, governance, staffing, referrals, assessments, therapeutic modalities in place, nutritional practices, and treatment protocols were collected. RESULTS: The results highlight the diversity of programming available but also the lack of a unified approach to intensive eating disorder treatment in youth. CONCLUSIONS: This report provides important baseline data that offers a framework that programs can use to come together to establish assessment and treatment protocols as well as a process for outcome evaluation. Continued collaboration will be essential moving forward to ensure Canadian youth, regardless of geographic location, receive the necessary treatment required to attain and sustain recovery. PMID- 24223052 TI - Adherence to psychostimulant medication in children with attention deficit/hyperactivity disorder: the role of attitudes. AB - OBJECTIVE: To investigate how attitudes towards psychostimulant medication influence the adherence to psychostimulant treatment in children with Attention Deficit/Hyperactivity Disorder (ADHD). METHOD: Thirty-three children with ADHD were prospectively recruited to take part in this study. The children and their parents filled questionnaires at both baseline and at a three-month follow-up to assess the severity of ADHD symptoms in the child and attitudes towards psychostimulant medication. Adherence to medication was assessed through standardized interviews of parents. RESULTS: Parental perceived psychosocial benefits of psychostimulant medication at the three-month follow-up were found to be positive predictors of adherence to medication. Parental perceived psychosocial benefits of medication at the three-month follow-up was in turn predicted by parental medication acceptability at three months and child's perceived psychosocial benefits of medication at three-months. CONCLUSION: Improving parents' awareness of psychosocial benefits of psychostimulant medication may increase adherence to psychostimulant medication in children with ADHD. Age of the child and severity of symptoms did not significantly affect medication adherence. PMID- 24223053 TI - First Manic Episode in an 11 Year-old Girl. AB - OBJECTIVE: We present the case of an 11 year-old girl admitted to the Centre hospitalier universitaire de Sherbrooke for a first manic episode. METHOD: Differential diagnoses of adjustment disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder were considered but eliminated. RESULTS: No organic etiology was detected. Her condition rapidly remitted with aripiprazole 3mg. After her discharge, she suffered a relapse due to instability of her living conditions and was rehospitalized. CONCLUSION: Mania is a difficult diagnosis in youths due to its nonspecific symptoms, rare prepubertal occurrence, and diagnostic complexity. Despite ongoing research, there is little conclusive information on the impact of psychosocial stressors on the evolution of early-onset bipolar disorder. PMID- 24223054 TI - Assessing Understanding and Obtaining Consent from Adults with Intellectual Disabilities for a Health Promotion Study. AB - People with intellectual disabilities are often excluded from research, in part because they may be perceived as lacking capacity to provide informed consent. A requirement of informed decision making about research participation is ability to understand the study description and disclosures presented during the consent process. The authors' aims were to determine the extent to which study participants with intellectual disabilities were able to answer questions about key aspects of study disclosures, identify ways in which people who provided appropriate answers for all of the questions differed from those who had difficulty with one or more of the questions, and examine patterns of responses to see if certain issues were more difficult to understand than others. The authors piloted a short set of questions to assess the extent to which adults with intellectual disabilities were able to answer questions about key aspects of a health promotion study. More than half of study participants correctly answered all of the questions. For those not able to answer all questions, identifying potential risks of being in the study proved the most challenging. The findings indicate that many people with intellectual disabilities likely can provide their own consent to participate in low risk studies. PMID- 24223055 TI - A valid approach in refractory glossodynia: a single-institution 5-year experience treating with Japanese traditional herbal (kampo) medicine. AB - Glossodynia is often refractory to conventional medicine, and there is only limited evidence to guide clinicians in its management. Patients with refractory glossodynia are often introduced to Japanese traditional herbal (Kampo) medicine experts under such circumstances because Kampo medicine has become known in Japan to be effective in treating a wide variety of symptoms refractory to conventional medicine. Herein, we report our single-institution 5-year experience treating patients with Kampo medicine for primary glossodynia that was refractory to conventional medicine. We found that 69.2% of patients reported a beneficial effect of Kampo medicine on glossodynia, and the average onset of improvement was 8.0 +/- 7.7 weeks after starting Kampo treatment. The top two frequently used Kampo medicines for glossodynia were seinetsuhokito and mibakuekkito among high responders who showed a decrease of severity by 50% or more. The top four most overlapped herbs among effective Kampo medicines for glossodynia were Glycyrrhiza Root, Ginseng Root, Hoelen, and Atractylodes (lancea) Rhizome, which compose an essential Kampo prescription called shikunshito. Although more research is required to further clarify the effectiveness of Kampo medicine, it has valid efficacy even in cases of glossodynia that remain incurable by conventional treatments. PMID- 24223056 TI - Anti-Inflammatory Effect of Supercritical-Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnen. AB - The aim of this study was to analyze the chemical composition and investigate the anti-inflammatory property of the supercritical-carbon dioxide extract from flowers and buds of C. indicum (CISCFE). The anti-inflammatory effect was evaluated in four animal models including xylene-induced mouse ear edema, acetic acid-induced mouse vascular permeability, carrageenan-induced mouse hind paw edema, and cotton pellet-induced rat granuloma formation. The results indicated that CISCFE significantly attenuated xylene-induced ear edema, decreased acetic acid-induced capillary permeability, reduced carrageenan-induced paw, and inhibited the cotton pellet-induced granuloma formation in a dose-dependent manner. Histopathologically, CISCFE abated inflammatory response of the edema paw. Preliminary mechanistic studies demonstrated that CISCFE decreased the MDA level via increasing the activities of anti-oxidant enzymes (SOD, GPx, and GRd), attenuated the productions of NF- kappa B, TNF- alpha , IL-1 beta , IL-6, PGE2 and NO, and suppressed the activities of iNOS and COX-2. In phytochemical study, 35 compounds were identified by GC-MS, and 5 compounds (chlorogenic acid, luteolin-7-glucoside, linarin, luteolin and acacetin) were reconfirmed and quantitatively determined by HPLC-PAD. This paper firstly analyzed the chemical composition by combining GC-MS with HPLC-PAD and explored possible mechanisms for the anti-inflammatory effect of CISCFE. PMID- 24223057 TI - Si Shen Wan Inhibits mRNA Expression of Apoptosis-Related Molecules in p38 MAPK Signal Pathway in Mice with Colitis. AB - Si Shen Wan (SSW) is used to effectively treat ulcerative colitis (UC) as a formula of traditional Chinese medicine. To explore the mechanism of SSW inhibited apoptosis of colonic epithelial cell, the study observed mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway in colonic mucosa in colitis mice treated with SSW. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice; meanwhile, the mice were administrated daily either SSW (5 g/kg) or p38 MAPK inhibitor (2 mg/kg) or vehicle (physiological saline) for 10 days. While microscopical evaluation was observed, apoptosis rate of colonic epithelial cell and mRNA expression of apoptosis-related molecules were tested. Compared with colitis mice without treatment, SSW alleviated colonic mucosal injuries and decreased apoptosis rate of colonic epithelial cell, while the mRNA expressions of p38 MAPK, p53, caspase 3, c-jun, c-fos, Bax, and TNF- alpha were decreased in the colonic mucosa in colitis mice treated with SSW, and Bcl-2 mRNA and the ratio of Bcl-2/Bax were increased. The present study demonstrated that SSW inhibited mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway to downregulate colonic epithelial cells apoptosis in colonic mucosa in mice with colitis. PMID- 24223058 TI - Synergistic inhibition of angiogenesis by artesunate and captopril in vitro and in vivo. AB - Inhibition of angiogenesis represents one major strategy of cancer chemotherapy. In the present investigation, we investigated the synergism of artesunate and captopril to inhibit angiogenesis. Artesunate is an antimalarial derivative of artemisinin from the Chinese medicinal plant, Artemisia annua L., which also reveals profound anticancer activity in vitro and in vivo. Captopril is an angiotensin I-converting (ACE) inhibitor, which is well established in Western academic medicine. Both compounds inhibited migration of human umbilical vein endothelial cells (HUVECs) in vitro. The combination of both drugs resulted in synergistically inhibited migration. Whereas artesunate inhibited HUVEC growth in the XTT assay, captopril did not, indicating independent modes of action. We established a chorioallantoic membrane (CAM) assay of quail embryos (Coturnix coturnix L.) and a computer-based evaluation routine for quantitative studies on vascularization processes in vivo. Artesunate and captopril inhibited blood vessel formation and growth. For the first time, we demonstrated that both drugs revealed synergistic effects when combined. These results may also have clinical impact, since cardiovascular diseases and cancer frequently occur together in older cancer patients. Therefore, comorbid patients may take advantage, if they take captopril to treat cardiovascular symptoms and artesunate to treat cancer. PMID- 24223059 TI - Evaluation of aromatic plants and compounds used to fight multidrug resistant infections. AB - Traditional medicine plays a vital role for primary health care in India, where it is widely practiced to treat various ailments. Among those obtained from the healers, 78 medicinal plants were scientifically evaluated for antibacterial activity. Methanol extract of plants (100 MU g of residue) was tested against the multidrug resistant (MDR) Gram-negative and Gram-positive bacteria. Forty seven plants showed strong activity against Burkholderia pseudomallei (strain TES and KHW) and Staphylococcus aureus, of which Tragia involucrata L., Citrus acida Roxb. Hook.f., and Aegle marmelos (L.) Correa ex Roxb. showed powerful inhibition of bacteria. Eighteen plants displayed only a moderate effect, while six plants failed to provide any evidence of inhibition against the tested bacteria. Purified compounds showed higher antimicrobial activity than crude extracts. The compounds showed less toxic effect to the human skin fibroblasts (HEPK) cells than their corresponding aromatic fractions. Phytochemical screening indicates that the presence of various secondary metabolites may be responsible for this activity. Most of the plant extracts contained high levels of phenolic or polyphenolic compounds and exhibited activity against MDR pathogens. In conclusion, plants are promising agents that deserve further exploration. Lead molecules available from such extracts may serve as potential antimicrobial agents for future drug development to combat diseases caused by the MDR bacterial strains as reported in this study. PMID- 24223060 TI - Antibacterial Activity of Rhus javanica against Methicillin-Resistant Staphylococcus aureus. AB - In the present study, the leaves of Rhus javanica (R. javanica) were extracted with ethanol, and we investigated the antimicrobial activity of the ethanol extract of R. javanica against methicillin-resistant Staphylococcus aureus (MRSA). Control groups were treated with media containing 0.1% DMSO. The ethanol extract of R. javanica inhibited the growth of MRSA at concentrations ranging from 0.05 to 0.2 mg/mL and inhibited acid production at concentrations higher than 0.1 mg/mL (P < 0.05). MRSA biofilm formation was determined by scanning electron microscopy and safranin staining. The ethanol extract of R. javanica inhibited the formation of MRSA biofilms at concentrations higher than 0.05 mg/mL. In confocal laser scanning microscopy, high concentration (0.4-1.6 mg/mL) of R. javanica extract showed bactericidal effect in a dose-dependent manner. In real-time PCR analysis, R. javanica extract showed the inhibition of the genetic expression of virulence factors such as mecA, sea, agrA, and sarA in MRSA. Preliminary phytochemical analysis revealed the strong presence of phenolics. These results suggest that R. javanica may be a useful medicinal plant for inhibiting MRSA, which may be related to the presence of phenolics in the R. javanica extract. PMID- 24223061 TI - Inhibitory Effect of Dodonaea viscosa var. angustifolia on the Virulence Properties of the Oral Pathogens Streptococcus mutans and Porphyromonas gingivalis. AB - Aim. This study investigated the effect of Dodonaea viscosa var. angustifolia (DVA) on the virulence properties of cariogenic Streptococcus mutans and Porphyromonas gingivalis implicated in periodontal diseases. Methods. S. mutans was cultured in tryptone broth containing a crude leaf extract of DVA for 16 hours, and the pH was measured after 10, 12, 14, and 16 h. Biofilms of S. mutans were grown on glass slides for 48 hours and exposed to plant extract for 30 minutes; the adherent cells were reincubated and the pH was measured at various time intervals. Minimum bactericidal concentration of the extracts against the four periodontal pathogens was determined. The effect of the subinhibitory concentration of plant extract on the production of proteinases by P. gingivalis was also evaluated. Results. DVA had no effect on acid production by S. mutans biofilms; however, it significantly inhibited acid production in planktonic cells. Periodontal pathogens were completely eliminated at low concentrations ranging from 0.09 to 0.02 mg/mL of crude plant extracts. At subinhibitory concentrations, DVA significantly reduced Arg-gingipain (24%) and Lys-gingipain (53%) production by P. gingivalis (P <= 0.01). Conclusions. These results suggest that DVA has the potential to be used to control oral infections including dental caries and periodontal diseases. PMID- 24223062 TI - Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers. AB - The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the mean C max of midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0-12, C max, and t 1/2 of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A. PMID- 24223063 TI - Systematic reviews and meta-analyses of traditional chinese medicine must search chinese databases to reduce language bias. AB - Systematic reviews (SRs) that fail to search non-English databases may miss relevant studies and cause selection bias. The bias may be particularly severe in SRs of traditional Chinese medicine (TCM) as most randomized controlled trials (RCT) in TCM are published and accessible only in Chinese. In this study we investigated how often Chinese databases were not searched in SRs of TCM, how many trials were missed, and whether a bias may occur if Chinese databases were not searched. We searched 5 databases in English and 3 in Chinese for RCTs of Chinese herbal medicine for coronary artery disease and found that 96.64% (115/119) eligible studies could be identified only from Chinese databases. In a random sample of 80 Cochrane reviews on TCM, we found that Chinese databases were only searched in 43 or 53.75%, in which almost all the included studies were identified from Chinese databases. We also compared SRs of the same topic and found that they may draw a different conclusion if Chinese databases were not searched. In conclusion, an overwhelmingly high percentage of eligible trials on TCM could only be identified in Chinese databases. Reviewers in TCM are suggested to search Chinese databases to reduce potential selection bias. PMID- 24223064 TI - Are Nouns Learned Before Verbs? Infants Provide Insight into a Longstanding Debate. AB - For decades, a spirited debate has existed over whether infants' remarkable capacity to learn words is shaped primarily by universal features of human language or by specific featuers of the particulare native language they are acquiring. A strong focus for this debate has been a well-documented difference in early word learning: Infants' success in learning verbs lags behind their success in learning nouns.. In this review, we articulate both sides of the debate and summarize new cross-linguistic evidence from infants that underscores the role of universal features and begins to clarify the impact of distinctly different languages on early language and conceptual development. PMID- 24223065 TI - Bacteriophage types of methicillin-resistant Staphylococcus aureus in a tertiary care hospital. AB - BACKGROUND: Phage typing had been utilised extensively to characterise methicillin-resistant Staphylococcus aureus (MRSA) outbreak strains in the past. It is an invaluable tool even today to monitor emergence and dissemination of MRSA strains. AIMS: The aim of this study was to determine the prevalent phage types of MRSA in south India and the association between phage types, antibiotic resistance pattern and risk factors. METHOD: A total of 48 non-duplicate MRSA strains recovered from various clinical samples during January to December, 2010 were tested against a panel of anti-staphylococcal antibiotics. Phage typing was carried out at the National Staphylococcal Phage Typing Centre, New Delhi. Out of 48, 32 hospitalised patients were followed up for risk factors and response to empirical and post sensitivity antibiotic therapy. The risk factors were compared with a control group of 30 patients with methicillin sensitive Staphylococcus aureus (MSSA) infection. RESULTS: Amongst the five prevalent phage types, 42E was most common (52%), followed by a non-typable variant (22.9%), 42E/47/54/75 (16.6%), 42E/47 (6.2%) and 47 (2%). Phage type 42E was the predominant strain in all wards and OPDs except in the ICU where 42E/47/54/75 was most common. Although not statistically significant, strain 42E/47/54/75 (n=8) showed higher resistance to all drugs, except ciprofloxacin and amikacin, and were mostly D-test positive (87.5%) compared to the 42E strain (32%). Duration of hospital stay, intravenous catheterisation and breach in skin were the most significant risk factors for MRSA infection. CONCLUSION: We found MRSA strain diversity in hospital wards with differences in their antibiotic susceptibility pattern. The findings may impact infection control and antibiotic policy significantly. PMID- 24223066 TI - Orbital myiasis caused by green bottle fly. AB - An 80-year-old farmer, presented with large, maggot infested ulceration involving the medial part of the right upper lid. The left eye was phthisical. There was history of untreated traumatic laceration of the right upper lid. Mechanical removal of maggots was done under turpentine coverage with regular antibiotic dressing. Microbiological examination of maggots revealed the larvae to be of Lucilia sericata (green bottle fly). The ulceration completely healed in two weeks following manual removal of maggots and regular dressing. Orbital myiasis is an uncommon clinical condition, with isolated case reports in literature. PMID- 24223067 TI - Tongue cleaner, an unusual foreign body in the urethra: A case report. AB - INTRODUCTION: Various cases of self-inflicted foreign body insertion into the urethra have been reported in adult males. The most common motive for such acts has been postulated as autoerotic stimulation, psychiatric illness or intoxication. CASE PRESENTATION: A 40-year-old male presented with a partially inserted tongue cleaner in his urethra with one end projecting from the urethral meatus and with a history of bleeding and pain. After a gentle attempt of removal using local anaesthetic gel the patient was scheduled for its surgical removal under anaesthesia. CONCLUSION: Large complex foreign bodies may be not amenable to endoscopic removal and may warrant open surgical procedure. Urethral stricture should be suspected in such patients. A psychiatric visit should be recommended for all adult males with self-inflicted foreign body in the urethra. PMID- 24223068 TI - Variation in the lobar pattern of the right and left lungs: A case report. AB - The right lung has three lobes and two fissures while the left lung has two lobes and one fissure. During a routine dissection we observed a variant complete fissure and three incomplete fissures in the right lung while the left lung presented with a variant transverse fissure separating the superior lingual and anterior bronchopulmonary segments. In the right lung, the incomplete fissures lie between the apical and posterior bronchopulmonary segments; medial and lateral bronchopulmonary segments; apical and basal bronchopulmonary segments. The complete variant fissure separates the medial basal bronchopulmonary segment from the remaining basal segments. Such variant fissures and lobes are clinically important in cases of lobotomy. PMID- 24223069 TI - Compressive myeloradiculopathy from bony metastasis as the initial presentation of poorly differentiated adenocarcinoma stomach - a case report. AB - Carcinoma of the stomach rarely disseminates to bone. We report a case of compressive myeloradiculopathy from extensive metastases to the spine, which on evaluation originated from adenocarcinoma of the stomach. Magnetic resonance imaging of the spine showed osteolytic and osteosclerotic metastases. Gastrointestinal endoscopy revealed ulcerative growth in the stomach that on biopsy showed poorly differentiated adenocarcinoma. This case is unique in that the initial presentation of gastric cancer itself was bony metastases without any gastrointestinal symptoms or liver involvement. Moreover, metastases were osteosclerotic as well, which is against the general belief that gastric cancer produces only osteolytic secondaries. PMID- 24223070 TI - Vascular leiomyosarcoma of thigh - A rare tumour at an unusual site. AB - Leiomyosarcomas of vascular origin are rare. They originate from the smooth muscles of tunica media of major blood vessels. The majority of such tumours arising in the extremities affect the femoral vascular bundle. There is limited knowledge and experience of the clinical presentation, pathological reports and results of treatment of this type of tumour. A case of primary leiomyosarcoma of femoral vein is being reported from a subtropical region of India that developed over the right thigh of a 35-year-old male farmer and was clinically diagnosed as benign soft tissue tumour. The diagnosis was confirmed by histopathology and immunohistochemistry. PMID- 24223072 TI - Generalised staphylococcal pustulosis in a neonate: A case report. AB - Pustular eruptions in a neonate are mostly benign, but several are serious and have infectious aetiology. A detailed history, complete physical examination and careful assessment of the lesions are essential for diagnosis. The need to investigate every neonate with pustules for an infectious aetiology is emphasised. This case of generalised pustulosis in a neonate is reported as it is an uncommon presentation of Staphylococcus aureus infection, diagnostic difficulty caused by atypical skin lesions and similarity of clinical features with other causes of neonatal pustular diseases. PMID- 24223071 TI - India towards diabetes control: Key issues. AB - The problem of mass diabetes is steadily increasing everyday. This editorial introduces key issues that need to be addressed to support the effective control of diabetes in India as well as globally. Issues like awareness generation for risk reduction, frequency of monitoring for selected parameters, standards for monitoring chronic complications in patients with diabetes, and current recommended targets of various parameters, amongst others, are presented along with extensions to the vaccinations recommended for diabetic patients. PMID- 24223073 TI - An overview of Ross Prentice's contributions to statistical science. AB - Ross Prentice's work has had the most profound impact on the theory and practice of statistics. His research interests range from survival analysis, longitudinal data analysis, epidemiologic designs and analysis, to genomic studies. His contributions are so broad and so deep that it would be impossible to provide a comprehensive review in any limited amount of space. In this commentary, I will attempt to give a brief tour of some of his statistical work, focusing on ten of my favorite papers of his. I will describe the main ideas in those papers and their influence on the directions of statistical research and on the designs and analysis of medical studies. I will mention a few stories along the way. PMID- 24223075 TI - Effects of Air Pollution on Asthma Hospitalization Rates in Different Age Groups in Metropolitan Cities of Korea. AB - Many studies have shown associations between air pollution and asthma admissions in Korea, but have not reported whether these effects differ by age classification. The purpose of this study was to determine whether air pollution effects on asthmatic hospital admissions are different by three age groups (years): children (less than 15), adults (15-64; reference group), and the elderly (over 65). Daily time-series data from seven metropolitan cities in South Korea were analyzed in two stages. In the first stage, relative asthma morbidity rates associated with air pollution were estimated for each city and age group, using semi-parametric log-linear regression. In the second stage, estimates from all seven cities were combined by age group using Bayesian hierarchical modeling. The effects of exposure to particulate matter <10 micrometers in aerodynamic diameter (PM10), carbon monoxide (CO) and nitrogen dioxide (NO2) varied significantly by age groups. Using adults as the referent, the relative rate (RR) of asthma admissions with 10MUg/m3 increase of PM10 is 1.5% (95%CI: 0.1-2.8%) lower for children, and 1.3% (95% CI: 0.7-1.9%) higher for the elderly; RR with 1ppm increase of CO is 1.9% (95% CI: 0.3-3.8%) lower for children; RR with 1ppb increase of NO2(1ppb) is 0.5% (95% CI: 0.3-0.7%) higher for the elderly. No significant age group difference in relative rate was found for ozone or sulfur dioxide. PMID- 24223076 TI - The use of a written assessment checklist for the provision of emergency contraception via community pharmacies: a simulated patient study. AB - BACKGROUND: The Pharmaceutical Society of Australia recommends use of a written assessment checklist prior to supply of emergency contraception by pharmacists. OBJECTIVE: The aim of this research was to determine the prevalence of use of a written assessment checklist by community pharmacists and secondly, to ascertain the effect of the checklist on appropriate assessment and supply. METHODS: Three female simulated patients visited 100 randomly selected pharmacies requesting supply of 'the morning after pill'. Information provided when assessed by the pharmacist was that she had missed one inactive pill of her regular hormonal contraception. The amount of assessment provided and the appropriateness of supply were used as comparative outcome measures. RESULTS: Eighty-three pharmacies used a written assessment checklist. Twenty-four of the pharmacies visited provided the appropriate outcome of non-supply. Pharmacies that used a written assessment checklist provided a greater quantity and consistency of assessment (11.3 +/-2.5 v. 6.5 +/-3.8 questions, p<0.0001) but this did not result in an improved frequency of an appropriate outcome (20%, n=16 v. 23%, n=3). CONCLUSIONS: While a written patient assessment checklist improved the quantity and consistency of patient assessment, it did not improve the advice provided by community pharmacies when handling requests for emergency contraception. PMID- 24223077 TI - Evaluation of the supply of antifungal medication for the treatment of vaginal thrush in the community pharmacy setting: a randomized controlled trial. AB - BACKGROUND: The Pharmaceutical Society of Australia have developed "guidance" for the supply of several medicines available without prescription to the general public. Limited research has been published assessing the effect of these guidelines on the provision of medication within the practice of pharmacy. OBJECTIVE: To assess appropriate supply of non-prescription antifungal medications for the treatment of vaginal thrush in community pharmacies, with and without a guideline. A secondary aim was to describe the assessment and counseling provided to patients when requesting this medication. METHODS: A randomized controlled trial was undertaken whereby two simulated patients conducted visits to 100 randomly selected community pharmacies in a metropolitan region. A product-based request for fluconazole (an oral antifungal that has a guideline was compared to a product-based request for clotrimazole (a topical antifungal without a guideline). The same patient details were used for both requests. Outcome measures of the visits were the appropriateness of supply and referral to a medical practitioner. RESULTS: Overall 16% (n=16) of visits resulted in an appropriate outcome; 10% (n=5) of fluconozaole requests compared with 22% (n=11) of clotrimazole requests (chi-square=2.68, p=0.10). There was a difference in the type of assessment performed by pharmacy staff between visits for fluconazole and clotrimazole. A request for clotrimazole resulted in a significant increase in frequency in regards to assessment of the reason for the request (chi-square=8.57, p=0.003), symptom location (chi-square=8.27, p=0.004), and prior history (chi-square=5.09, p=0.02). CONCLUSIONS: Overall practice was poor, with the majority of pharmacies inappropriately supplying antifungal medication. New strategies are required to improve current practice of community pharmacies for provision of non-prescription antifungals in the treatment of vaginal thrush. PMID- 24223074 TI - Biological networks in ischemic tolerance - rethinking the approach to clinical conditioning. AB - The adaptive response (conditioning) to environmental stressors evokes evolutionarily conserved programs in uni- and multicellular organisms that result in increased fitness and resistance to stressor induced injury. Although the concept of conditioning has been around for a while, its translation into clinical therapies targeting neurovascular diseases has only recently begun. The slow pace of clinical adoption might be partially explained by our poor understanding of underpinning mechanisms and of the complex responses of the organism to the stressor. At the 2(nd) Translational Preconditioning Meeting participants engaged in an intense discussion addressing whether the time has come to more aggressively implement clinical conditioning protocols in the treatment of cerebrovascular diseases or whether it would be better to wait until preclinical data would help to minimize clinical empiricism. This review addresses the complex involvement of biological networks in establishing ischemic tolerance at the organism level using two clinically promising conditioning modalities, namely remote ischemic preconditioning, and per- or post conditioning, as examples. PMID- 24223078 TI - Analysis of written advertising material distributed through community pharmacies in Riyadh, Saudi Arabia. AB - BACKGROUND: Advertising is a crucial component of pharmaceutical industry promotion. Research indicates that information on advertisement materials might be inadequate, inaccurate, biased, and misleading. OBJECTIVE: To analyse and critically assess the information presented in print pharmaceutical advertisements in Saudi Arabia. METHODS: Pharmaceutical advertisements were collected from 280 community pharmacies in Riyadh city, Saudi Arabia. The advertisements were evaluated using criteria derived from the Saudi Food and Drug Authority (SFDA) regulation, the World Health Organization (WHO) ethical medicinal drug promotion criteria, and other principles reported in similar studies. The data were extracted independently by two of the researchers using a standardized assessment form. RESULTS: One hundred eighty five printed advertisements were included in the final sample. Approximately half of the advertisements (n = 94, 51%) were for over-the-counter (OTC) medications, and 71 (38%) were for prescription-only medication. Information such as the name of active ingredients was available in 168 (90.8%) advertisements, therapeutic uses were mentioned in 156 (98.7%) of analysed advertisements. Safety information related to side effects, precautions, and major interactions were stated in 53 (28.5%), 58 (31%), and 33 (16.5%) advertisements, respectively. Only 119 advertisements (64%) provided references for information presented. CONCLUSIONS: Our findings suggest that print advertisements do not convey all the information necessary for safe prescribing. These results have implications for the regulation of drug advertising and the continuing education of pharmacists. PMID- 24223079 TI - Impact of educational intervention on knowledge of dispensers working at community pharmacies in Pakistan. AB - OBJECTIVE: To evaluate the impact of training of dispensers on knowledge of dispensers working at community pharmacies in context to storage temperature, prescription terminologies and status of medicines in Islamabad, Pakistan. METHODS: A randomized, controlled, blinded intervention study was designed and implemented. Before the implementation of intervention, a baseline study was performed to assess the knowledge of dispensers working at community pharmacies. The study population included all community pharmacy outlets in Islamabad. Pharmacies of Islamabad which were visited in pre intervention phase (n=118) were divided into two geographical regions: A (intervention) and B (control). Thirty pharmacies were randomly selected from each region. Keeping in view the results of the baseline study an educational intervention was designed to improve the knowledge of dispensers working at community pharmacies in Pakistan. RESULTS: A significant difference in the overall knowledge of dispensers was observed between the pre-post intervention groups. Knowledge of dispensers regarding storage of drugs, prescription terminologies and status of drugs was improved after the training. On the other hand no significant difference was observed between the pre-post control groups. CONCLUSIONS: The study has highlighted that improvements in knowledge of dispensers working at community pharmacies are possible through suitable interventions. But, results of interventions can only be sustainable through continuous monitoring and reinforcement of the training. PMID- 24223080 TI - Student pharmacists' career choices: a survey of three Nigerian schools of pharmacy. AB - BACKGROUND: There is little data on the preferences of pharmacy students as regards their future pharmacy job choices in Africa and this has created concerns amongst licensing bodies, employers and also the institutions they graduate from. OBJECTIVE: Career choices and factors that influence these choices of pre registration pharmacists were assessed. METHODS: Final and fourth year students from three schools of pharmacy were approached with a previously validated and employed questionnaire comprising questions on future job choices and reasons for that job choice. Data collected were subjected to descriptive and inferential analysis. RESULTS: Four hundred and eighty eight students took part in the study (response rate 71.5%). Majority (78.8%) was younger than 26 years and had a work experience (68.2%). Job flexibility was significantly more important to females, while younger students considered salary most important (p<0.05). Hospital and community practice were most preferred career choices. Other demographic factors (especially gender, marital status, previous degree and previous work experience) significantly affected career choices. CONCLUSIONS: Age, gender, and previous work experience affect career choices of graduating pharmacy students. Patient oriented practices (e.g. hospital and community) remain the most preferred careers. PMID- 24223081 TI - Effect of number and type of antidiabetes medications on adherence and glycemia of ambulatory type 2 diabetes patients in southwestern Nigeria. AB - OBJECTIVE: To determine the influence of number and type of antidiabetes medications on adherence and glycemia of ambulatory type 2 diabetes patients in southwestern Nigeria. METHODS: A cross-sectional study using pre-tested structured questionnaire among 176 consented patients recruited from the endocrinology clinics of two teaching hospitals between November, 2010 and January, 2011; and a retrospective review of case notes of the cohort for details of prescribed medications and blood glucose values. Descriptive statistics were used to summarize the data. Tests of proportions were evaluated using Chi-square or Fisher's exact test as appropriate. The differences in mean fasting blood glucose (FBG) between and among categorical variables were compared using student t-test and ANOVA respectively, with p<0.05 considered significant. RESULTS: Mean number of prescribed medications was 4.6 +/-1.4. Almost two thirds 103 (60.6%) were placed on >4 medications. Adherence was better among patients on >4 medications compared to those on <=4 medications (p=0.05). However, patients on >4 medications were mostly older adults (>60 years of age), and they were in the majority (66.7%) who had tertiary education compared to 33.3% of those on <=4 medications who had tertiary education (p=0.02). Adherence rates to antidiabetes medications were in the ranking of oral antidiabetes medications (OAM) alone (50.0%) > insulin plus OAM (44.0%) > insulin alone (41.7%) with no significant difference (p=0.77). There was a significant difference in mean FBG among patients on >4 medications (172.1 +/-61.1mg/dL) versus (198.8 +/-83.8mg/dL) among those on <=4 medications (p=0.02). CONCLUSIONS: Prescribing more than four medications is linked to improved adherence and glycemic outcome. However, age and educational background of patients are important factors that need to be considered when prescribing multiple medications for type 2 diabetes. PMID- 24223082 TI - Challenges to publishing pharmacy resident research projects from the perspectives of residency program directors and residents. AB - OBJECTIVE: To identify barriers to completing and publishing pharmacy residency research projects from the perspective of program directors and former residents. METHODS: This was a cross-sectional survey of pharmacy residency program directors and former post-graduate year one and two residents. Directors of pharmacy residency programs whose residents present their projects at the Western States Conference (n=216) were invited to complete an online survey and asked to forward the survey to former residents of their program in 2009, 2010, or 2011. The survey focused on four broad areas: 1) demographic characteristics of the residency programs, directors, and residents; 2) perceived value of the research project; 3) perceived barriers with various stages of research; and 4) self identified barriers to successful research project completion and publication. RESULTS: A total of 32 program directors and 98 residents completed the survey. The minority of programs offered formal residency research training. Both groups reported value in the research project as part of residency training. Significantly more directors reported obtaining institutional review board approval and working through the publication process as barriers to the research project (46.7% vs. 22.6% and 73.3% vs. 43.0%, respectively p<0.05) while residents were more likely to report collecting and analyzing the data as barriers (34.4% vs. 13.3% and 39.8% vs. 20.0%, respectively, p<0.05). Both groups self-identified time constraints and limitations in study design or quality of the study as barriers. However, while program directors also indicated lack of resident motivation (65.5%), residents reported lack of mentorship or program structural issues (43.3%). CONCLUSIONS: Overall, while both groups found value in the residency research projects, there were barriers identified by both groups. The results of this study may provide areas of opportunity for improving the quality and publication rates of resident research projects. PMID- 24223083 TI - Medication therapy management clinic: perception of healthcare professionals in a University medical center setting. AB - OBJECTIVE: To determine the overall perception and utilization of the pharmacist managed medication therapy management (MTM) clinic services, by healthcare professionals in a large, urban, university medical care setting. METHODS: This was a cross-sectional, anonymous survey sent to 195 healthcare professionals, including physicians, nurses, and pharmacists at The University of Illinois Outpatient Care Center to determine their perception and utilization of the MTM clinic. The survey consisted of 12 questions and was delivered through a secure online application. RESULTS: Sixty-two healthcare professionals (32%) completed the survey. 82% were familiar with the MTM clinic, and 63% had referred patients to the clinic. Medication adherence and disease state management was the most common reason for referral. Lack of knowledge on the appropriate referral procedure was the prominent reason for not referring patients to the MTM clinic. Of the providers that were aware of MTM services, 44% rated care as 'excellent', 44% as 'good', 5% as 'fair', and 0% stated 'poor'. Strengths of MTM clinic identified by healthcare providers included in-depth education to patients, close follow-up, and detailed medication reconciliation provided by MTM clinic pharmacists. Of those familiar with MTM clinic, recommendations included; increase marketing efforts to raise awareness of the MTM clinic service, create collaborative practice agreements between MTM pharmacists and physicians, and ensure that progress notes are more concise. CONCLUSIONS: In a large, urban, academic institution MTM clinic is perceived as a valuable resource to optimize patient care by providing patients with in-depth education as it relates to their prescribed medications and disease states. These identified benefits of MTM clinic lead to frequent patient referrals specifically for aid with medication adherence and disease state management. PMID- 24223084 TI - Erratum: "Manufacturing and wetting low-cost microfluidic cell separation devices" [Biomicrofluidics 7, 056501 (2013)]. AB - [This corrects the article on p. 056501 in vol. 7.]. PMID- 24223099 TI - N-butyl cyanoacrylate is very effective for massive haemorrhage during the perinatal period. AB - OBJECTIVE: The liquid embolic agent n-butyl cyanoacrylate (NBCA) is a tissue adhesive used as an immediate and permanent embolic agent when mixed with oil based contrast medium. In this study, the preservation of fertility with TAE using NBCA for massive haemorrhage during pregnancy or the peripartum period and the utility of this therapy were investigated. METHODS: Cases from January 2005 to October 2010 in which TAE was performed for massive haemorrhage in pregnant women, particularly during the peripartum period, were investigated. RESULTS: TAE was performed in 27 pregnant women. The embolic agent used was GS only in five cases, NBCA only in 19 cases, and additional embolization with NBCA when the effect with GS was insufficient in three cases, one each of abruptio placentae, cervical pregnancy, and uterine atony.A comparison of mean blood loss when each embolic agent was used for haemostasis showed a significant difference between cases in which GS only was used and cases in which NBCA only was used. In a comparison of mean transfusion volume, a significant difference was seen between cases in which both GS and NBCA were used and cases in which NBCA only was used. In a postoperative follow-up survey, menses resumed in eight patients, including four patients who later became pregnant and three who delivered. CONCLUSIONS: TAE with NBCA, which has an embolic effect unrelated to clotting dysfunction for massive haemorrhage during the peripartum period, is a minimally invasive and very effective treatment method for patients with severe DIC. PMID- 24223098 TI - Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. AB - Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered. PMID- 24223100 TI - Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells. AB - Acute myeloid leukemia (AML) is believed to arise from leukemic stem-like cells (LSC) making understanding the biological differences between LSC and normal stem cells (HSC) or common myeloid progenitors (CMP) crucial to understanding AML biology. To determine if protein expression patterns were different in LSC compared to other AML and CD34+ populations, we measured the expression of 121 proteins by Reverse Phase Protein Arrays (RPPA) in 5 purified fractions from AML marrow and blood samples: Bulk (CD3/CD19 depleted), CD34-, CD34+(CMP), CD34+CD38+ and CD34+CD38-(LSC). LSC protein expression differed markedly from Bulk (n =31 cases, 93/121 proteins) and CD34+ cells (n = 30 cases, 88/121 proteins) with 54 proteins being significantly different (31 higher, 23 lower) in LSC than in either Bulk or CD34+ cells. Sixty-seven proteins differed significantly between CD34+ and Bulk blasts (n = 69 cases). Protein expression patterns in LSC and CD34+ differed markedly from normal CD34+ cells. LSC were distinct from CD34+ and Bulk cells by principal component and by protein signaling network analysis which confirmed individual protein analysis. Potential targetable submodules in LSC included the proteins PU.1(SP1), P27, Mcl1, HIF1alpha, cMET, P53, Yap, and phospho-Stats 1, 5 and 6. Protein expression and activation in LSC differs markedly from other blast populations suggesting that studies of AML biology should be performed in LSC. PMID- 24223101 TI - New strategies to prolong the in vivo life span of iron-based contrast agents for MRI. AB - Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ~ 30 nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7 mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55 mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is 2-3 times higher than iron concentration obtained by the use of murine SPIO-loaded RBCs. PMID- 24223109 TI - Quantitative analysis of PiB-PET with FreeSurfer ROIs. AB - In vivo quantification of beta-amyloid deposition using positron emission tomography is emerging as an important procedure for the early diagnosis of the Alzheimer's disease and is likely to play an important role in upcoming clinical trials of disease modifying agents. However, many groups use manually defined regions, which are non-standard across imaging centers. Analyses often are limited to a handful of regions because of the labor-intensive nature of manual region drawing. In this study, we developed an automatic image quantification protocol based on FreeSurfer, an automated whole brain segmentation tool, for quantitative analysis of amyloid images. Standard manual tracing and FreeSurfer based analyses were performed in 77 participants including 67 cognitively normal individuals and 10 individuals with early Alzheimer's disease. The manual and FreeSurfer approaches yielded nearly identical estimates of amyloid burden (intraclass correlation = 0.98) as assessed by the mean cortical binding potential. An MRI test-retest study demonstrated excellent reliability of FreeSurfer based regional amyloid burden measurements. The FreeSurfer-based analysis also revealed that the majority of cerebral cortical regions accumulate amyloid in parallel, with slope of accumulation being the primary difference between regions. PMID- 24223110 TI - Social judgement in borderline personality disorder. AB - BACKGROUND: Borderline personality disorder (BPD) is a common and serious mental illness, associated with a high risk of suicide and self harm. Those with a diagnosis of BPD often display difficulties with social interaction and struggle to form and maintain interpersonal relationships. Here we investigated the ability of participants with BPD to make social inferences from faces. METHOD: 20 participants with BPD and 21 healthy controls were shown a series of faces and asked to judge these according to one of six characteristics (age, distinctiveness, attractiveness, intelligence, approachability, trustworthiness). The number and direction of errors made (compared to population norms) were recorded for analysis. RESULTS: Participants with a diagnosis of BPD displayed significant impairments in making judgements from faces. In particular, the BPD Group judged faces as less approachable and less trustworthy than controls. Furthermore, within the BPD Group there was a correlation between scores on the Childhood Trauma Questionnaire (CTQ) and bias towards judging faces as unapproachable. CONCLUSION: Individuals with a diagnosis of BPD have difficulty making appropriate social judgements about others from their faces. Judging more faces as unapproachable and untrustworthy indicates that this group may have a heightened sensitivity to perceiving potential threat, and this should be considered in clinical management and treatment. PMID- 24223111 TI - The suppression of WRKY44 by GIGANTEA-miR172 pathway is involved in drought response of Arabidopsis thaliana. AB - Water availability is an important environmental factor that controls flowering time. Many plants accelerate flowering under drought conditions, a phenomenon called drought escape. Four pathways are involved in controlling flowering time, but which ones participate in drought escape is not yet known. In this study, plants with loss-of-function mutations of GIGANTEA (GI) and CONSTANS (CO) exhibited abnormal drought-escape phenotypes. The peak mRNA levels of GI and FKF1 (Flavin-binding Kelch domain F box protein 1) and the mRNA levels of CO and FT (Flowering locus T) changed under drought stress. The microRNA factor miRNA172E was up-regulated by drought stress, and its up-regulation was dependent on GI, while other miRNA172s were not. Water-loss analyses indicated that gi mutants were more sensitive while miRNA172 over-expressing (miRNA172-OX) plants were less so to drought stress than wild-type plants. Digital gene expression and real-time PCR analyses showed that WRKY44 was down-regulated by GI and miRNA172. The WRKY44 protein could interact with TOE1 (a target of miRNA172) in a yeast two-hybrid system. We proposed that GI-miRNA172-WRKY44 may regulate drought escape and drought tolerance by affecting sugar signaling in Arabidopsis. PMID- 24223112 TI - Genetic relatedness among hepatitis A virus strains associated with food-borne outbreaks. AB - The genetic characterization of hepatitis A virus (HAV) strains is commonly accomplished by sequencing subgenomic regions, such as the VP1/P2B junction. HAV genome is not extensively variable, thus presenting opportunity for sharing sequences of subgenomic regions among genetically unrelated isolates. The degree of misrepresentation of phylogenetic relationships by subgenomic regions is especially important for tracking transmissions. Here, we analyzed whole-genome (WG) sequences of 101 HAV strains identified from 4 major multi-state, food-borne outbreaks of hepatitis A in the Unites States and from 14 non-outbreak-related HAV strains that shared identical VP1/P2B sequences with the outbreak strains. Although HAV strains with an identical VP1/P2B sequence were specific to each outbreak, WG were different, with genetic diversity reaching 0.31% (mean 0.09%). Evaluation of different subgenomic regions did not identify any other section of the HAV genome that could accurately represent phylogenetic relationships observed using WG sequences. The identification of 2-3 dominant HAV strains in 3 out of 4 outbreaks indicates contamination of the implicated food items with a heterogeneous HAV population. However, analysis of intra-host HAV variants from eight patients involved in one outbreak showed that only a single sequence variant established infection in each patient. Four non-outbreak strains were found closely related to strains from 2 outbreaks, whereas ten were genetically different from the outbreak strains. Thus, accurate tracking of HAV strains can be accomplished using HAV WG sequences, while short subgenomic regions are useful for identification of transmissions only among cases with known epidemiological association. PMID- 24223113 TI - HGF/SF increases number of skin melanocytes but does not alter quality or quantity of follicular melanogenesis. AB - Melanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) have extra follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old) C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR) to quantitate melanin, by transmission electron microscopy (TEM) for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma. PMID- 24223114 TI - An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology. AB - Zinc Finger Nucleases (ZFNs), famous for their ability to precisely and efficiently modify specific genomic loci, have been employed in numerous transgenic model organism and cell constructions. Here we employ the ZFNs technology, with homologous recombination (HR), to construct sequence-specific Amyloid Precursor Protein (APP) knock-in cells. With the use of ZFNs, we established APP knock in cell lines with gene-modification efficiencies of about 7%. We electroporated DNA fragment containing the promoter and the protein coding regions of the zinc finger nucleases into cells, instead of the plasmids, to avoid problems associated with off target homologous recombination, and adopted a pair of mutated FokI cleavage domains to reduce the toxic effects of the ZFNs on cell growth. Since over-expression of APP, or a subdomain of it, might lead to an immediately lethal effect, we used the Cre-LoxP System to regulate APP expression. Our genetically transformed cell lines, w5c1 and s12c8, showed detectable APP and Amyloid beta (Abeta) production. The Swedish double mutation in the APP coding sequence enhanced APP and Abeta abundance. What is more, the activity of the three key secretases in Abeta formation could be modulated, indicating that these transgenic cells have potential for drug screening to modify amyloid metabolism in cells. Our transformed cells could readily be propagated in culture and should provide an excellent experimental medium for elucidating aspects of the molecular pathogenesis of Alzheimer's disease, especially those concerning the amyloidogenic pathways involving mutations in the APP coding sequence. The cellular models may also serve as a tool for deriving potentially useful therapeutic agents. PMID- 24223115 TI - Glycemic variability is an independent predictive factor for development of hepatic fibrosis in nonalcoholic fatty liver disease. AB - Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM). We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT) and a continuous glucose monitoring system (CGMS). One hundred sixty-nine patients (68 female and 101 male patients) with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0-3). The proportion of patients with T2DM significantly gradually increased, HbA1c and the homeostasis model assessment of insulin resistance were significantly elevated, and 1,5-anhydroglucitol (1,5-AG) was remarkably decreased with the progression of fibrosis. In the 75gOGTT, both plasma glucose and insulin secretion were remarkably increased with the progression of fibrosis. The only factor significantly associated with advanced fibrosis was 1,5-AG (P = 0.008) as determined by multivariate logistic regression analysis. We next evaluated the changes in blood glucose during 24 hours by monitoring with the CGMS to confirm the relationship between glycemic variability and progression of fibrosis. Variability of median glucose, standard deviation of median glucose (P = 0.0022), maximum blood glucose (P = 0.0019), and DeltaMin-max blood glucose (P = 0.0029) were remarkably higher in severe fibrosis than in mild fibrosis. CONCLUSION: Hyperinsulinemia and hyperglycemia, especially glycemic variability, are important predictive factors in glucose impairment for the progression of hepatic fibrosis in NAFLD. PMID- 24223116 TI - Evidence that transition from health to psychotic disorder can be traced to semi ubiquitous environmental effects operating against background genetic risk. AB - BACKGROUND: In order to assess the importance of environmental and genetic risk on transition from health to psychotic disorder, a prospective study of individuals at average (n = 462) and high genetic risk (n = 810) was conducted. METHOD: A three-year cohort study examined the rate of transition to psychotic disorder. Binary measures indexing environmental exposure (combining urban birth, cannabis use, ethnicity and childhood trauma) and proxy genetic risk (high-risk sibling status) were used to model transition. RESULTS: The majority of high-risk siblings (68%) and healthy comparison subjects (60%) had been exposed to one or more environmental risks. The risk of transition in siblings (n = 9, 1.1%) was higher than the risk in healthy comparison subjects (n = 2, 0.4%; OR(adj) = 2.2,95%CI:5-10.3). All transitions (100%) were associated with environmental exposure, compared to 65% of non-transitions (p = 0.014), with the greatest effects for childhood trauma (OR(adj) = 34.4,95%CI:4.4-267.4), cannabis use (OR = 4.1,95%CI:1.1, 15.4), minority ethnic group (OR = 3.8,95%CI:1.2,12.8) and urban birth (OR = 3.7,95%CI:0.9,15.4). The proportion of transitions in the population attributable to environmental and genetic risk ranged from 28% for minority ethnic group, 45% for urban birth, 57% for cannabis use, 86% for childhood trauma, and 50% for high-risk sibling status. Nine out of 11 transitions (82%) were exposed to both genetic and environmental risk, compared to only 43% of non transitions (p = 0.03). CONCLUSION: Environmental risk associated with transition to psychotic disorder is semi-ubiquitous regardless of genetic high risk status. Careful prospective documentation suggests most transitions can be attributed to powerful environmental effects that become detectable when analysed against elevated background genetic risk, indicating gene-environment interaction. PMID- 24223117 TI - Broad-spectrum detection of H5 subtype influenza A viruses with a new fluorescent immunochromatography system. AB - Immunochromatography (IC) is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3) pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC) to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10-100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA) proteins (rHAs) belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans. PMID- 24223118 TI - On the definition of signal-to-noise ratio and contrast-to-noise ratio for FMRI data. AB - Signal-to-noise ratio, the ratio between signal and noise, is a quantity that has been well established for MRI data but is still subject of ongoing debate and confusion when it comes to fMRI data. fMRI data are characterised by small activation fluctuations in a background of noise. Depending on how the signal of interest and the noise are identified, signal-to-noise ratio for fMRI data is reported by using many different definitions. Since each definition comes with a different scale, interpreting and comparing signal-to-noise ratio values for fMRI data can be a very challenging job. In this paper, we provide an overview of existing definitions. Further, the relationship with activation detection power is investigated. Reference tables and conversion formulae are provided to facilitate comparability between fMRI studies. PMID- 24223119 TI - Diazotrophy in alluvial meadows of subarctic river systems. AB - There is currently limited understanding of the contribution of biological N2 fixation (diazotrophy) to the N budget of large river systems. This natural source of N in boreal river systems may partially explain the sustained productivity of river floodplains in Northern Europe where winter fodder was harvested for centuries without fertilizer amendments. In much of the world, anthropogenic pollution and river regulation have nearly eliminated opportunities to study natural processes that shaped early nutrient dynamics of large river systems; however, pristine conditions in northern Fennoscandia allow for the retrospective evaluation of key biochemical processes of historical significance. We investigated biological N2 fixation (diazotrophy) as a potential source of nitrogen fertility at 71 independent floodplain sites along 10 rivers and conducted seasonal and intensive analyses at a subset of these sites. Biological N2 fixation occurred in all floodplains, averaged 24.5 kg N ha(-1) yr(-1) and was down regulated from over 60 kg N ha(-1) yr(-1) to 0 kg N ha(-1) yr(-1) by river N pollution. A diversity of N2-fixing cyanobacteria was found to colonize surface detritus in the floodplains. The data provide evidence for N2 fixation to be a fundamental source of new N that may have sustained fertility at alluvial sites along subarctic rivers. Such data may have implications for the interpretation of ancient agricultural development and the design of contemporary low-input agroecosystems. PMID- 24223120 TI - Experimental modelling of the consequences of brief late gestation asphyxia on newborn lamb behaviour and brain structure. AB - Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient in utero asphyxia in late gestation fetal sheep, on the newborn lamb after birth. Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term), the cuff was inflated to induce umbilical cord occlusion (UCO), or sham (control). Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i) use all four legs, (ii) attain a standing position, (iii) find the udder, and (iv) successfully suckle--compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies. PMID- 24223121 TI - Expression of estrogen-related gene markers in breast cancer tissue predicts aromatase inhibitor responsiveness. AB - Aromatase inhibitors (AIs) are the most effective class of drugs in the endocrine treatment of breast cancer, with an approximate 50% treatment response rate. Our objective was to determine whether intratumoral expression levels of estrogen related genes are predictive of AI responsiveness in postmenopausal women with breast cancer. Primary breast carcinomas were obtained from 112 women who received AI therapy after failing adjuvant tamoxifen therapy and developing recurrent breast cancer. Tumor ERalpha and PR protein expression were analyzed by immunohistochemistry (IHC). Messenger RNA (mRNA) levels of 5 estrogen-related genes-AKR1C3, aromatase, ERalpha, and 2 estradiol/ERalpha target genes, BRCA1 and PR-were measured by real-time PCR. Tumor protein and mRNA levels were compared with breast cancer progression rates to determine predictive accuracy. Responsiveness to AI therapy-defined as the combined complete response, partial response, and stable disease rates for at least 6 months-was 51%; rates were 56% in ERalpha-IHC-positive and 14% in ERalpha-IHC-negative tumors. Levels of ERalpha, PR, or BRCA1 mRNA were independently predictive for responsiveness to AI. In cross-validated analyses, a combined measurement of tumor ERalpha and PR mRNA levels yielded a more superior specificity (36%) and identical sensitivity (96%) to the current clinical practice (ERalpha/PR-IHC). In patients with ERalpha/PR-IHC-negative tumors, analysis of mRNA expression revealed either non significant trends or statistically significant positive predictive values for AI responsiveness. In conclusion, expression levels of estrogen-related mRNAs are predictive for AI responsiveness in postmenopausal women with breast cancer, and mRNA expression analysis may improve patient selection. PMID- 24223122 TI - Rifampicin mono-resistance in Mycobacterium tuberculosis in KwaZulu-Natal, South Africa: a significant phenomenon in a high prevalence TB-HIV region. AB - SETTING: The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono resistance resistance (RMR) have recently been reported from South Africa and other countries. OBJECTIVE: This laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR. DESIGN: MTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis. RESULTS: RMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25-29 year age category. CONCLUSION: We report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as recommended by the SA NDOH TB guidelines as well as WHO. We suggest that two sputum samples should be obtained at the first visit. The second sputum sample should be stored at 4 degrees C. The latter sample is then readily available for performing additional DST (phenotypic or genotypic) for 2nd lines drugs, resulting in a decreased waiting period for DST results to become available. PMID- 24223123 TI - Studies in RF power communication, SAR, and temperature elevation in wireless implantable neural interfaces. AB - Implantable neural interfaces are designed to provide a high spatial and temporal precision control signal implementing high degree of freedom real-time prosthetic systems. The development of a Radio Frequency (RF) wireless neural interface has the potential to expand the number of applications as well as extend the robustness and longevity compared to wired neural interfaces. However, it is well known that RF signal is absorbed by the body and can result in tissue heating. In this work, numerical studies with analytical validations are performed to provide an assessment of power, heating and specific absorption rate (SAR) associated with the wireless RF transmitting within the human head. The receiving antenna on the neural interface is designed with different geometries and modeled at a range of implanted depths within the brain in order to estimate the maximum receiving power without violating SAR and tissue temperature elevation safety regulations. Based on the size of the designed antenna, sets of frequencies between 1 GHz to 4 GHz have been investigated. As expected the simulations demonstrate that longer receiving antennas (dipole) and lower working frequencies result in greater power availability prior to violating SAR regulations. For a 15 mm dipole antenna operating at 1.24 GHz on the surface of the brain, 730 uW of power could be harvested at the Federal Communications Commission (FCC) SAR violation limit. At approximately 5 cm inside the head, this same antenna would receive 190 uW of power prior to violating SAR regulations. Finally, the 3-D bio-heat simulation results show that for all evaluated antennas and frequency combinations we reach FCC SAR limits well before 1 degrees C. It is clear that powering neural interfaces via RF is possible, but ultra-low power circuit designs combined with advanced simulation will be required to develop a functional antenna that meets all system requirements. PMID- 24223124 TI - Contamination of public buses with MRSA in Lisbon, Portugal: a possible transmission route of major MRSA clones within the community. AB - In a previous study we have shown that public buses in Oporto, the second largest city in Portugal, were highly contaminated with MRSA. Here we describe the results of a similar study performed in another urban area of Portugal-Lisbon, the capital. Between May 2011 and May 2012, hand touched surfaces of 199 public buses in Lisbon were screened for MRSA contamination. Subsequently, the hands of 575 passengers who frequently use these bus lines were also screened. All hand carriers of MRSA were further screened for nasal carriage. The isolates were characterized by PFGE, staphylococcal cassette chromosome (SCC) mec typing, spa typing, MLST and were tested for the presence of mecA, Panton-Valentine leukocidin and arginine catabolic mobile element genes. MRSA contamination was shown in 72 buses (36.2%). The majority of the isolates belonged to three major clones: Clone A was identified as EMRSA-15 defined by pattern PFGE A, spa types t2357/t747/t025/t379/t910, ST22, and SCCmec IVh (n = 21; 29%). Clone B was the New York/Japan clone characterized by PFGE B-t002/t10682-ST5-II (n = 15; 21%). Clone C included isolates with characteristics of the international community acquired USA300 or related clones, PFGE C-t008-ST8-IVa/IVc/IVg/IVnt/VI (n = 19; 26%). The first two clones are currently the two major lineages circulating in Portuguese hospitals. The hands of 15 individuals were contaminated with MRSA belonging to the nosocomial clones A or B. Eleven of these individuals were not nasal carriers of MRSA and all but one had travelled by public transportation, namely by bus, prior to sampling. In conclusion, public buses in two major cities in Portugal are often contaminated with MRSA representing clones dominant in hospitals in the particular geographic area. MRSA contamination of public transport and the transfer of the bacteria to the hands of passengers may represent a route through which hospital-acquired MRSA clones may spread to the community. PMID- 24223125 TI - Brief exposure to a self-paced computer-based reading programme and how it impacts reading ability and behaviour problems. AB - Basic literacy skills underlie much future adult functioning, and are targeted in children through a variety of means. Children with reading problems were exposed either to a self-paced computer programme that focused on improving phonetic ability, or underwent a classroom-based reading intervention. Exposure was limited to 3 40-min sessions a week, for six weeks. The children were assessed in terms of their reading, spelling, and mathematics abilities, as well as for their externalising and internalising behaviour problems, before the programme commenced, and immediately after the programme terminated. Relative to the control group, the computer-programme improved reading by about seven months in boys (but not in girls), but had no impact on either spelling or mathematics. Children on the programme also demonstrated fewer externalising and internalising behaviour problems than the control group. The results suggest that brief exposure to a self-paced phonetic computer-teaching programme had some benefits for the sample. PMID- 24223126 TI - Optimal scaling of digital transcriptomes. AB - Deep sequencing of transcriptomes has become an indispensable tool for biology, enabling expression levels for thousands of genes to be compared across multiple samples. Since transcript counts scale with sequencing depth, counts from different samples must be normalized to a common scale prior to comparison. We analyzed fifteen existing and novel algorithms for normalizing transcript counts, and evaluated the effectiveness of the resulting normalizations. For this purpose we defined two novel and mutually independent metrics: (1) the number of "uniform" genes (genes whose normalized expression levels have a sufficiently low coefficient of variation), and (2) low Spearman correlation between normalized expression profiles of gene pairs. We also define four novel algorithms, one of which explicitly maximizes the number of uniform genes, and compared the performance of all fifteen algorithms. The two most commonly used methods (scaling to a fixed total value, or equalizing the expression of certain 'housekeeping' genes) yielded particularly poor results, surpassed even by normalization based on randomly selected gene sets. Conversely, seven of the algorithms approached what appears to be optimal normalization. Three of these algorithms rely on the identification of "ubiquitous" genes: genes expressed in all the samples studied, but never at very high or very low levels. We demonstrate that these include a "core" of genes expressed in many tissues in a mutually consistent pattern, which is suitable for use as an internal normalization guide. The new methods yield robustly normalized expression values, which is a prerequisite for the identification of differentially expressed and tissue-specific genes as potential biomarkers. PMID- 24223127 TI - In nonagenarians, acute kidney injury predicts in-hospital mortality, while heart failure predicts hospital length of stay. AB - BACKGROUND/AIMS: The elderly constitute an increasing proportion of admitted patients worldwide. We investigate the determinants of hospital length of stay and outcomes in patients aged 90 years and older. METHODS: We retrospectively analyzed all admitted patients aged >90 years from the general medical wards in a tertiary referral medical center between August 31, 2009 and August 31, 2012. Patients' clinical characteristics, admission diagnosis, concomitant illnesses at admission, and discharge diagnosis were collected. Each patient was followed until discharge or death. Multivariate logistic regression analysis was utilized to study factors associated with longer hospital length of stay (>7 days) and in hospital mortality. RESULTS: A total of 283 nonagenarian in-patients were recruited, with 118 (41.7%) hospitalized longer than one week. Nonagenarians admitted with pneumonia (p = 0.04) and those with lower Barthel Index (p = 0.012) were more likely to be hospitalized longer than one week. Multivariate logistic regression analysis revealed that patients with lower Barthel Index (odds ratio [OR] 0.98; p = 0.021) and those with heart failure (OR 3.05; p = 0.046) had hospital stays >7 days, while patients with lower Barthel Index (OR 0.93; p = 0.005), main admission nephrologic diagnosis (OR 4.83; p = 0.016) or acute kidney injury (OR 30.7; p = 0.007) had higher in-hospital mortality. CONCLUSION: In nonagenarians, presence of heart failure at admission was associated with longer hospital length of stay, while acute kidney injury at admission predicted higher hospitalization mortality. Poorer functional status was associated with both prolonged admission and higher in-hospital mortality. PMID- 24223128 TI - Insulin stimulates translocation of human GLUT4 to the membrane in fat bodies of transgenic Drosophila melanogaster. AB - The fruit fly Drosophila melanogaster is an excellent model system for studies of genes controlling development and disease. However, its applicability to physiological systems is less clear because of metabolic differences between insects and mammals. Insulin signaling has been studied in mammals because of relevance to diabetes and other diseases but there are many parallels between mammalian and insect pathways. For example, deletion of Drosophila Insulin-Like Peptides resulted in 'diabetic' flies with elevated circulating sugar levels. Whether this situation reflects failure of sugar uptake into peripheral tissues as seen in mammals is unclear and depends upon whether flies harbor the machinery to mount mammalian-like insulin-dependent sugar uptake responses. Here we asked whether Drosophila fat cells are competent to respond to insulin with mammalian like regulated trafficking of sugar transporters. Transgenic Drosophila expressing human glucose transporter-4 (GLUT4), the sugar transporter expressed primarily in insulin-responsive tissues, were generated. After expression in fat bodies, GLUT4 intracellular trafficking and localization were monitored by confocal and total internal reflection fluorescence microscopy (TIRFM). We found that fat body cells responded to insulin with increased GLUT4 trafficking and translocation to the plasma membrane. While the amplitude of these responses was relatively weak in animals reared on a standard diet, it was greatly enhanced in animals reared on sugar-restricted diets, suggesting that flies fed standard diets are insulin resistant. Our findings demonstrate that flies are competent to mobilize translocation of sugar transporters to the cell surface in response to insulin. They suggest that Drosophila fat cells are primed for a response to insulin and that these pathways are down-regulated when animals are exposed to constant, high levels of sugar. Finally, these studies are the first to use TIRFM to monitor insulin-signaling pathways in Drosophila, demonstrating the utility of TIRFM of tagged sugar transporters to monitor signaling pathways in insects. PMID- 24223129 TI - Mycoplasma hyorhinis activates the NLRP3 inflammasome and promotes migration and invasion of gastric cancer cells. AB - BACKGROUND: Mycoplasma hyorhinis (M.hyorhinis, M.hy) is associated with development of gastric and prostate cancers. The NLRP3 inflammasome, a protein complex controlling maturation of important pro-inflammatory cytokines interleukin (IL)-1beta and IL-18, is also involved in tumorigenesis and metastasis of various cancers. METHODOLOGY/PRINCIPAL FINDINGS: To clarify whether M.hy promoted tumor development via inflammasome activation, we analyzed monocytes for IL-1beta and IL-18 production upon M.hy challenge. When exposed to M.hy, human monocytes exhibited rapid and robust IL-1beta and IL-18 secretion. We further identified that lipid-associated membrane protein (LAMP) from M.hy was responsible for IL-1beta induction. Applying competitive inhibitors, gene specific shRNA and gene targeted mice, we verified that M.hy induced IL-1beta secretion was NLRP3-dependent in vitro and in vivo. Cathepsin B activity, K(+) efflux, Ca(2+) influx and ROS production were all required for the NLRP3 inflammasome activation by M.hy. Importantly, it is IL-1beta but not IL-18 produced from macrophages challenged with M.hy promoted gastric cancer cell migration and invasion. CONCLUSIONS: Our data suggest that activation of the NLRP3 inflammasome by M.hy may be associated with its promotion of gastric cancer metastasis, and anti-M.hy therapy or limiting NLRP3 signaling could be effective approach for control of gastric cancer progress. PMID- 24223130 TI - The facilitating role of chemotherapy in the palliative phase of cancer: qualitative interviews with advanced cancer patients. AB - OBJECTIVE: To explore the extent to which patients have a directing role in decisions about chemotherapy in the palliative phase of cancer and (want to) anticipate on the last stage of life. DESIGN: Qualitative interview study. METHODS: In depth-interviews with 15 patients with advanced colorectal or breast cancer at the medical oncology department in a Dutch teaching hospital; interviews were analysed following the principles of thematic content-analysis. RESULTS: All patients reported to know that the chemotherapy they received was with palliative intent. Most of them did not express the wish for information about (other) treatment options and put great trust in their physicians' treatment advice. The more patients were aware of the severity of their disease, the more they seemed to 'live their life' in the present and enjoy things besides having cancer. Such living in the present seemed to be facilitated by the use of chemotherapy. Patients often considered the 'chemotherapy-free period' more stressful than periods when receiving chemotherapy despite their generally improved physical condition. Chemotherapy (regardless of side-effects) seemed to shift patients' attention away from the approaching last stage of life. Interestingly, although patients often discussed advance care planning, they were reluctant to bring on end-of-life issues that bothered them at that specific moment. Expressing real interest in people 'as a person' was considered an important element of appropriate care. CONCLUSIONS: Fearing their approaching death, patients deliberately focus on living in the present. Active (chemotherapy) treatment facilitates this focus, regardless of the perceived side effects. However, if anxiety for what lies ahead is the underlying reason for treatment, efforts should be made in assisting patients to find other ways to cope with this fear. Simultaneously, such an approach may reduce the use of burdensome and sometimes costly treatment in the last stage of life. PMID- 24223131 TI - Quantifying clinical HPV4 dose inefficiencies in a safety net population. AB - PURPOSE: HPV4 is the most expensive vaccine requiring three appropriately timed doses to provide maximal efficacy against two oncogenic HPV types. The primary purpose of this study is to quantify the use of HPV4 vaccine in a safety net health care system in terms of its inefficiencies. METHODS: A retrospective study of HPV4 dosing from 2006-2009, among females 10-26 years old who sought care in a safety net health care system was conducted to determine dose usage patterns among those at highest risk for cervical cancer. Dose descriptors abstracted from the electronic medical record (EMR) included timing and number in series as well as characteristics of the person to whom and visit at which the dose was given. Dose inefficiencies were separated into "less than three doses" and "mistimed doses" for analysis. RESULTS: The majority (66%) of HPV4 doses administered were insufficient to induce the maximal immune response necessary for HPV infection prevention. Among on-time doses, 58% were singleton or doublet doses. Mistimed doses accounted for 19% of all doses administered with late intervals being more common than early intervals among those receiving more than one dose (9% vs. 4%, p<0.001). Third doses were mistimed twice as often as second doses (10% vs. 5%, p<0.001). Black women were more likely to have a mistimed second dose and Hispanic women more likely to have a mistimed third dose compared to white women (OR = 1.70 (95% CI: 1.11, 2.61 and 2.44 (1.19, 5.00), respectively). The HPV4 only visit type at which HPV4 was initiated was the most significant predictor of on-time doublet completion. CONCLUSIONS: In a safety net health care system the large inefficiencies associated with HPV4 vaccination must be addressed in order to maximize our patient's cervical cancer prevention. PMID- 24223132 TI - Connectivity of tiger (Panthera tigris) populations in the human-influenced forest mosaic of Central India. AB - Today, most wild tigers live in small, isolated Protected Areas within human dominated landscapes in the Indian subcontinent. Future survival of tigers depends on increasing local population size, as well as maintaining connectivity between populations. While significant conservation effort has been invested in increasing tiger population size, few initiatives have focused on landscape-level connectivity and on understanding the effect different landscape elements have on maintaining connectivity. We combined individual-based genetic and landscape ecology approaches to address this issue in six protected areas with varying tiger densities and separation in the Central Indian tiger landscape. We non invasively sampled 55 tigers from different protected areas within this landscape. Maximum-likelihood and Bayesian genetic assignment tests indicate long range tiger dispersal (on the order of 650 km) between protected areas. Further geo-spatial analyses revealed that tiger connectivity was affected by landscape elements such as human settlements, road density and host-population tiger density, but not by distance between populations. Our results elucidate the importance of landscape and habitat viability outside and between protected areas and provide a quantitative approach to test functionality of tiger corridors. We suggest future management strategies aim to minimize urban expansion between protected areas to maximize tiger connectivity. Achieving this goal in the context of ongoing urbanization and need to sustain current economic growth exerts enormous pressure on the remaining tiger habitats and emerges as a big challenge to conserve wild tigers in the Indian subcontinent. PMID- 24223133 TI - Modelling parasite transmission in a grazing system: the importance of host behaviour and immunity. AB - Parasitic helminths present one of the most pervasive challenges to grazing herbivores. Many macro-parasite transmission models focus on host physiological defence strategies, omitting more complex interactions between hosts and their environments. This work represents the first model that integrates both the behavioural and physiological elements of gastro-intestinal nematode transmission dynamics in a managed grazing system. A spatially explicit, individual-based, stochastic model is developed, that incorporates both the hosts' immunological responses to parasitism, and key grazing behaviours including faecal avoidance. The results demonstrate that grazing behaviour affects both the timing and intensity of parasite outbreaks, through generating spatial heterogeneity in parasite risk and nutritional resources, and changing the timing of exposure to the parasites' free-living stages. The influence of grazing behaviour varies with the host-parasite combination, dependent on the development times of different parasite species and variations in host immune response. Our outputs include the counterintuitive finding that under certain conditions perceived parasite avoidance behaviours (faecal avoidance) can increase parasite risk, for certain host-parasite combinations. Through incorporating the two-way interaction between infection dynamics and grazing behaviour, the potential benefits of parasite induced anorexia are also demonstrated. Hosts with phenotypic plasticity in grazing behaviour, that make grazing decisions dependent on current parasite burden, can reduce infection with minimal loss of intake over the grazing season. This paper explores how both host behaviours and immunity influence macro parasite transmission in a spatially and temporally heterogeneous environment. The magnitude and timing of parasite outbreaks is influenced by host immunity and behaviour, and the interactions between them; the incorporation of both regulatory processes is required to fully understand transmission dynamics. Understanding of both physiological and behavioural defence strategies will aid the development of novel approaches for control. PMID- 24223134 TI - Confronting uncertainty in wildlife management: performance of grizzly bear management. AB - Scientific management of wildlife requires confronting the complexities of natural and social systems. Uncertainty poses a central problem. Whereas the importance of considering uncertainty has been widely discussed, studies of the effects of unaddressed uncertainty on real management systems have been rare. We examined the effects of outcome uncertainty and components of biological uncertainty on hunt management performance, illustrated with grizzly bears (Ursus arctos horribilis) in British Columbia, Canada. We found that both forms of uncertainty can have serious impacts on management performance. Outcome uncertainty alone--discrepancy between expected and realized mortality levels- led to excess mortality in 19% of cases (population-years) examined. Accounting for uncertainty around estimated biological parameters (i.e., biological uncertainty) revealed that excess mortality might have occurred in up to 70% of cases. We offer a general method for identifying targets for exploited species that incorporates uncertainty and maintains the probability of exceeding mortality limits below specified thresholds. Setting targets in our focal system using this method at thresholds of 25% and 5% probability of overmortality would require average target mortality reductions of 47% and 81%, respectively. Application of our transparent and generalizable framework to this or other systems could improve management performance in the presence of uncertainty. PMID- 24223135 TI - The NR4A2 nuclear receptor is recruited to novel nuclear foci in response to UV irradiation and participates in nucleotide excision repair. AB - Ultraviolet radiation (UVR) is one of the most common mutagens encountered by humans and induces the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproduct (6-4PP) lesions in the genomic DNA. To prevent the accumulation of deleterious mutations these lesions must be efficiently repaired, primarily by nucleotide excision repair. We have previously demonstrated that the NR4A family of nuclear receptors are crucial mediators of the DNA repair function of the MC1R signalling pathway in melanocytes. Here we explore the role of the NR4A2 protein in the DNA repair process further. Using EYFP tagged-NR4A2 we have demonstrated a UVR induced recruitment to distinct nuclear foci where they co-localise with known DNA repair proteins. We reveal that the N-terminal domain of the receptor is required for this translocation and identify a role for p38 and PARP signalling in this process. Moreover disruption of the functional integrity of the Ligand Binding Domain of the receptor by deleting the terminal helix 12 effectively blocks co-localisation of the receptor with DNA repair factors. Restored co-localisation of the mutant receptor with DNA repair proteins in the presence of a Histone Deacetylase Inhibitor suggests that impaired chromatin accessibility underpins the mis-localisation observed. Finally NR4A2 over-expression facilitated a more efficient clearance of UVR induced CPD and 6-4PP lesions. Taken together these data uncover a novel role for the NR4A nuclear receptors as direct facilitators of nucleotide excision repair. PMID- 24223136 TI - Wolbachia infections mimic cryptic speciation in two parasitic butterfly species, Phengaris teleius and P. nausithous (Lepidoptera: Lycaenidae). AB - Deep mitochondrial divergence within species may result from cryptic speciation, from phylogeographic isolation or from endosymbiotic bacteria like Wolbachia that manipulate host reproduction. Phengaris butterflies are social parasites that spend most of their life in close relationship with ants. Previously, cryptic speciation has been hypothesised for two Phengaris species based on divergent mtDNA sequences. Since Phengaris species are highly endangered, the existence of cryptic species would have drastic consequences for conservation and management. We tested for cryptic speciation and alternative scenarios in P. teleius and P. nausithous based on a comprehensive sample across their Palaearctic ranges using COI gene sequences, nuclear microsatellites and tests for Wolbachia. In both species a deep mitochondrial split occurring 0.65-1.97 myrs ago was observed that did not correspond with microsatellite data but was concordant with Wolbachia infection. Haplotypes previously attributed to cryptic species were part of the Wolbachia-infected clades. In both species remaining phylogeographic structure was largely consistent between mitochondrial and nuclear genomes. In P. teleius several mitochondrial and nuclear groups were observed in East Asia while a single haplogroup and nuclear cluster prevailed across continental Eurasia. Neutrality tests suggested rapid demographic expansion into that area. In contrast, P. nausithous had several mitochondrial and nuclear groups in Europe, suggesting a complex phylogeographic history in the western part of the species range. We conclude that deep intraspecific divergences found in DNA barcode studies do not necessarily need to represent cryptic speciation but instead can be due to both infection by Wolbachia and phylogeographic structure. PMID- 24223137 TI - Surgical stress delays prostate involution in mice. AB - Androgens control growth of prostate epithelial cells and androgen deprivation induces apoptosis, leading to prostate involution. We investigated the effects of surgical stress on prostate involution induced by androgen ablation and determined the underlying mechanisms. Androgen ablation in mice was induced by surgical castration and administration of the anti-androgenic drugs bicalutamide and MDV3100. Surgical stress was induced by sham castration under isoflurane anesthesia. Surgical stress delayed apoptosis and prostate involution induced by anti-androgenic drugs. These effects of stress were prevented by administering the selective beta2-adrenoreceptor antagonist ICI118,551 and were also blocked in BAD(3SA/WT) mice expressing phosphorylation-deficient mutant BAD3SA. These results indicate that apoptosis and prostate involution in response to androgen ablation therapy could be delayed by surgical stress via the beta2 adrenoreceptor/BAD signaling pathway. Thus, surgery could interfere with androgen ablation therapy, whereas administration of beta2-adrenoreceptor antagonists may enhance its efficacy. PMID- 24223138 TI - Forever love: the Hitherto earliest record of copulating insects from the middle jurassic of China. AB - BACKGROUND: Mating behaviors have been widely studied for extant insects. However, cases of mating individuals are particularly rare in the fossil record of insects, and most of them involved preservation in amber while only in rare cases found in compression fossils. This considerably limits our knowledge of mating position and genitalia orientation during the Mesozoic, and hinders our understanding of the evolution of mating behaviors in this major component of modern ecosystems. PRINCIPAL FINDING: Here we report a pair of copulating froghoppers, Anthoscytina perpetua sp. nov., referable to the Procercopidae, from the Middle Jurassic of northeastern China. They exhibit belly-to-belly mating position as preserved, with male's aedeagus inserting into the female's bursa copulatrix. Abdominal segments 8 to 9 of male are disarticulated suggesting these segments were twisted and flexed during mating. Due to potential taphonomic effect, we cannot rule out that they might have taken side-by-side position, as in extant froghoppers. Genitalia of male and female, based on paratypes, show symmetric structures. CONCLUSIONS/SIGNIFICANCE: Our findings, consistent with those of extant froghoppers, indicate froghoppers' genitalic symmetry and mating position have remained static for over 165 million years. PMID- 24223139 TI - Post-transcriptional regulator Hfq binds catalase HPII: crystal structure of the complex. AB - We report a crystal structure of Hfq and catalase HPII from Escherichia coli. The post-transcriptional regulator Hfq plays a key role in the survival of bacteria under stress. A small non-coding RNA (sRNA) DsrA is required for translation of the stationary phase sigma factor RpoS, which is the central regulator of the general stress response. Hfq facilitates efficient translation of rpoS mRNA, which encodes RpoS. Hfq helps in the function of other specific proteins involved in RNA processing, indicating its versatility in the cell. However, structural information regarding its interactions with partners is missing. Here we obtained crystals of Hfq and HPII complexes from cell lysates following attempts to overexpress a foreign membrane protein. HPII is one of two catalases in E. coli and its mRNA is transcribed by an RNA polymerase holoenzyme containing RpoS, which in turn is under positive control of small non-coding RNAs and of the RNA chaperone Hfq. This sigma factor is known to have a pronounced effect on the expression of HPII. The crystal structure reveals that a Hfq hexamer binds each subunit of a HPII tetramer. Each subunit of the Hfq hexamer exhibits a unique binding mode with HPII. The hexamer of Hfq interacts via its distal surface. The proximal and distal surfaces are known to specifically bind different sRNAs, and binding of HPII could affect Hfq function. Hfq-HPII complexation has no effect on catalase HPII activity. PMID- 24223140 TI - Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing. AB - BACKGROUND: Sympathetic activity involves the pathogenesis of atrial fibrillation (AF). Renal sympathetic denervation (RSD) decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive. The aim of this study was to identify the effects of RSD on AF inducibility induced by hyper sympathetic activity in a canine model. METHODS: To establish a hyper-sympathetic tone canine model of AF, sixteen dogs were subjected to stimulation of left stellate ganglion (LSG) and rapid atrial pacing (RAP) for 3 hours. Then animals in the RSD group (n = 8) underwent radiofrequency ablation of the renal sympathetic nerve. The control group (n = 8) underwent the same procedure except for ablation. AF inducibility, effective refractory period (ERP), ERP dispersion, heart rate variability and plasma norepinephrine levels were measured at baseline, after stimulation and after ablation. RESULTS: LSG stimulation combined RAP significantly induced higher AF induction rate, shorter ERP, larger ERP dispersion at all sites examined and higher plasma norepinephrine levels (P<0.05 in all values), compared to baseline. The increased AF induction rate, shortened ERP, increased ERP dispersion and elevated plasma norepinephrine levels can be almost reversed by RSD, compared to the control group (P<0.05). LSG stimulation combined RAP markedly shortened RR-interval and standard deviation of all RR intervals (SDNN), Low-frequency (LF), high-frequency (HF) and LF/HF ratio (P<0.05). These changes can be reversed by RSD, compared to the control group (P<0.05). CONCLUSIONS: RSD significantly reduced AF inducibility and reversed the atrial electrophysiological changes induced by hyper-sympathetic activity. PMID- 24223141 TI - Breastmilk cell and fat contents respond similarly to removal of breastmilk by the infant. AB - Large inter- and intra-individual variations exist in breastmilk composition, yet factors associated with these variations in the short-term are not well understood. In this study, the effects of breastfeeding on breastmilk cellular and biochemical content were examined. Serial breastmilk samples (~5 mL) were collected from both breasts of breastfeeding women before and immediately after the first morning breastfeed, and then at 30-minute intervals for up to 3 hours post-feed on 2-4 mornings per participant. The infant fed from one breast only at each feed. Effects of pump versus hand expression for samples were evaluated. A consistent response pattern of breastmilk cell and fat contents to breastmilk removal was observed. Maximum fat and cell levels were obtained 30 minutes post feed (P<0.01), with up to 8-fold increase in fat and 12-fold increase in cell content compared to the pre-feed values, and then they gradually decreased. Breastmilk cell viability and protein concentration did not change with feeding (P>0.05), although large intra-individual variability was noted for protein. Expression mode for samples did not influence breastmilk composition (P>0.05). It is concluded that breastmilk fat content, and thus breast fullness, is closely associated with breastmilk cell content. This will now form the basis for standardization of sampling protocols in lactation studies and investigation of the mechanisms of milk synthesis and cell movement into breastmilk. Moreover, these findings generate new avenues for clinical interventions exploring growth and survival benefits conferred to preterm infants by providing the highest in fat and cells milk obtained at 30 min post-expression. PMID- 24223142 TI - Regulation of Ggamma-globin gene by ATF2 and its associated proteins through the cAMP-response element. AB - The upstream Ggamma-globin cAMP-response element (G-CRE) plays an important role in regulating Ggamma-globin expression through binding of ATF2 and its DNA binding partners defined in this study. ATF2 knockdown resulted in a significant reduction of gamma-globin expression accompanied by decreased ATF2 binding to the G-CRE. By contrast, stable ATF2 expression in K562 cells increased gamma-globin transcription which was reduced by ATF2 knockdown. Moreover, a similar effect of ATF2 on gamma-globin expression was observed in primary erythroid progenitors. To understand the role of ATF2 in gamma-globin expression, chromatographically purified G-CRE/ATF2-interacting proteins were subjected to mass spectrometry analysis; major binding partners included CREB1, cJun, Brg1, and histone deacetylases among others. Immunoprecipitation assays demonstrated interaction of these proteins with ATF2 and in vivo GCRE binding in CD34(+) cells undergoing erythroid differentiation which was correlated with gamma-globin expression during development. These results suggest synergism between developmental stage specific recruitments of the ATF2 protein complex and expression of gamma-globin during erythropoiesis. Microarray studies in K562 cells support ATF2 plays diverse roles in hematopoiesis and chromatin remodeling. PMID- 24223143 TI - Impact of male infanticide on the social structure of mountain gorillas. AB - Infanticide can be a major influence upon the social structure of species in which females maintain long-term associations with males. Previous studies have suggested that female mountain gorillas benefit from residing in multimale groups because infanticide occurs when one-male groups disintegrate after the dominant male dies. Here we measure the impact of infanticide on the reproductive success of female mountain gorillas, and we examine whether their dispersal patterns reflect a strategy to avoid infanticide. Using more than 40 years of data from up to 70% of the entire population, we found that only 1.7% of the infants that were born in the study had died from infanticide during group disintegrations. The rarity of such infanticide mainly reflects a low mortality rate of dominant males in one-male groups, and it does not dispel previous observations that infanticide occurs during group disintegrations. After including infanticide from causes other than group disintegrations, infanticide victims represented up to 5.5% of the offspring born during the study, and they accounted for up to 21% of infant mortality. The overall rates of infanticide were 2-3 times higher in one-male groups than multimale groups, but those differences were not statistically significant. Infant mortality, the length of interbirth intervals, and the age of first reproduction were not significantly different between one-male versus multimale groups, so we found no significant fitness benefits for females to prefer multimale groups. In addition, we found limited evidence that female dispersal patterns reflect a preference for multimale groups. If the strength of selection is modest for females to avoid group disintegrations, than any preference for multimale groups may be slow to evolve. Alternatively, variability in male strength might give some one-male groups a lower infanticide risk than some multimale groups, which could explain why both types of groups remain common. PMID- 24223144 TI - Diversified microbiota of meconium is affected by maternal diabetes status. AB - OBJECTIVES: This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status. METHODS: The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis. RESULTS: All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group. CONCLUSIONS: Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients. PMID- 24223145 TI - Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin. AB - In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs) with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be <=1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66 induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex. PMID- 24223146 TI - The impact of cognitive testing on the welfare of group housed primates. AB - Providing cognitive challenges to zoo-housed animals may provide enriching effects and subsequently enhance their welfare. Primates may benefit most from such challenges as they often face complex problems in their natural environment and can be observed to seek problem solving opportunities in captivity. However, the extent to which welfare benefits can be achieved through programmes developed primarily for cognitive research is unknown. We tested the impact of voluntary participation cognitive testing on the welfare of a socially housed group of crested macaques (Macaca nigra) at the Macaque Study Centre (Marwell Zoo). First, we compared the rate of self-directed and social behaviours on testing and non testing days, and between conditions within testing days. Minimal differences in behaviour were found when comparing testing and non-testing days, suggesting that there was no negative impact on welfare as a result of cognitive testing. Lipsmacking behaviours were found to increase and aggressive interaction was found to decrease in the group as a result of testing. Second, social network analysis was used to assess the effect of testing on associations and interactions between individuals. The social networks showed that testing subjects increased their association with others during testing days. One interpretation of this finding could be that providing socially housed primates with an opportunity for individuals to separate from the group for short periods could help mimic natural patterns of sub-group formation and reunion in captivity. The findings suggest, therefore, that the welfare of captive primates can be improved through the use of cognitive testing in zoo environments. PMID- 24223147 TI - Aging brain from a network science perspective: something to be positive about? AB - To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being. PMID- 24223148 TI - Risk factors associated with default from multi- and extensively drug-resistant tuberculosis treatment, Uzbekistan: a retrospective cohort analysis. AB - BACKGROUND: The Medecins Sans Frontieres project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. METHODS: A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing >=60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi square test and in multivariate analysis with logistic regression. RESULTS: 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6 9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001). CONCLUSIONS: Default from treatment was high and increased with programme scale up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default. PMID- 24223150 TI - Dietary behaviour and socioeconomic position: the role of physical activity patterns. AB - BACKGROUND: The positive association between education level and health outcomes can be partly explained by dietary behaviour. We investigated the associations between education and several indices of food intake and potential influencing factors, placing special emphasis on physical-activity patterns, using a representative sample of the German adult population. METHODS: The German National Health Interview and Examination Survey 1998 (GNHIES98) involved 7,124 participants aged between 18 and 79. Complete information on the exposure (education) and outcome (nutrition) variables was available for 6,767 persons. The associations between 'education' and indices of 'sugar-rich food', 'fat-rich food', 'fruit-and-vegetable' and 'alcohol' intake were analysed separately for men and women using multivariate logistic regression analysis. Odds ratios (OR) of education level on nutrition outcomes were calculated and adjusted for age, region (former East/West Germany), occupation, income and other influencing factors such as physical activity indicators. RESULTS: Men and women with only a primary education had a more frequent intake of sugar-rich and fat-rich foods and a less frequent intake of fruit and vegetables and alcohol than people with a tertiary education. 'Physical work activity' partly explained the associations between education and sugar-rich food intake. The interference with physical work activity was stronger among men than women. No significant associations between education and energy-dense food intake were observed in the retirement-age group of persons aged 65+ and among persons with low energy expenditure. CONCLUSIONS: In Germany, adults with a low level of education report that they consume energy dense foods more frequently - and fruit and vegetables and alcohol less frequently - than adults with a high education level. High levels of physical work activity among adults with a low education level may partly explain why they consume more energy-dense foods. PMID- 24223149 TI - Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality. AB - Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumor biology. We made the first gene knock-in (gki) mouse with a serine to alanine point mutation at the DPP9 active site (S729A). Weaned heterozygote DPP9 (wt/S729A) pups from 110 intercrosses were indistinguishable from wild-type littermates. No homozygote DPP9 (S729A/S729A) weaned mice were detected. DPP9 (S729A/S729A) homozygote embryos, which were morphologically indistinguishable from their wild-type littermate embryos at embryonic day (ED) 12.5 to ED 17.5, were born live but these neonates died within 8 to 24 hours of birth. All neonates suckled and contained milk spots and were of similar body weight. No gender differences were seen. No histological or DPP9 immunostaining pattern differences were seen between genotypes in embryos and neonates. Mouse embryonic fibroblasts (MEFs) from DPP9 (S729A/S729A) ED13.5 embryos and neonate DPP9 (S729A/S729A) mouse livers collected within 6 hours after birth had levels of DPP9 protein and DPP9 related proteases that were similar to wild-type but had less DPP9/DPP8-derived activity. These data confirmed the absence of DPP9 enzymatic activity due to the presence of the serine to alanine mutation and no compensation from related proteases. These novel findings suggest that DPP9 enzymatic activity is essential for early neonatal survival in mice. PMID- 24223151 TI - HLA typing from 1000 genomes whole genome and whole exome illumina data. AB - Specific HLA genotypes are known to be linked to either resistance or susceptibility to certain diseases or sensitivity to certain drugs. In addition, high accuracy HLA typing is crucial for organ and bone marrow transplantation. The most widespread high resolution HLA typing method used to date is Sanger sequencing based typing (SBT), and next generation sequencing (NGS) based HLA typing is just starting to be adopted as a higher throughput, lower cost alternative. By HLA typing the HapMap subset of the public 1000 Genomes paired Illumina data, we demonstrate that HLA-A, B and C typing is possible from exome sequencing samples with higher than 90% accuracy. The older 1000 Genomes whole genome sequencing read sets are less reliable and generally unsuitable for the purpose of HLA typing. We also propose using coverage % (the extent of exons covered) as a quality check (QC) measure to increase reliability. PMID- 24223152 TI - Notch-1 signaling regulates microglia activation via NF-kappaB pathway after hypoxic exposure in vivo and in vitro. AB - Neuroinflammation mediated by the activated microglia is suggested to play a pivotal role in the pathogenesis of hypoxic brain injury; however, the underlying mechanism of microglia activation remains unclear. Here, we show that the canonical Notch signaling orchestrates microglia activation after hypoxic exposure which is closely associated with multiple pathological situations of the brain. Notch-1 and Delta-1 expression in primary microglia and BV-2 microglial cells was significantly elevated after hypoxia. Hypoxia-induced activation of Notch signaling was further confirmed by the concomitant increase in the expression and translocation of intracellular Notch receptor domain (NICD), together with RBP-Jkappa and target gene Hes-1 expression. Chemical inhibition of Notch signaling with N-[N-(3,5-difluorophenacetyl)-1-alany1- S-phenyglycine t butyl ester (DAPT), a gamma-secretase inhibitor, effectively reduced hypoxia induced upregulated expression of most inflammatory mediators. Notch inhibition also reduced NF-kappaB/p65 expression and translocation. Remarkably, Notch inhibition suppressed expression of TLR4/MyD88/TRAF6 pathways. In vivo, Notch signaling expression and activation in microglia were observed in the cerebrum of postnatal rats after hypoxic injury. Most interestingly, hypoxia-induced upregulation of NF-kappaB immunoexpression in microglia was prevented when the rats were given DAPT pretreatment underscoring the interrelationship between Notch signaling and NF-kappaB pathways. Taken together, we conclude that Notch signaling is involved in regulating microglia activation after hypoxia partly through the cross talk between TLR4/MyD88/TRAF6/NF-kappaB pathways. Therefore, Notch signaling may serve as a prospective target for inhibition of microglia activation known to be implicated in brain damage in the developing brain. PMID- 24223153 TI - Direct association of heat shock protein 20 (HSPB6) with phosphoinositide 3 kinase (PI3K) in human hepatocellular carcinoma: regulation of the PI3K activity. AB - HSP20 (HSPB6), one of small heat shock proteins (HSPs), is constitutively expressed in various tissues and has several functions. We previously reported that the expression levels of HSP20 in human hepatocellular carcinoma (HCC) cells inversely correlated with the progression of HCC, and that HSP20 suppresses the growth of HCC cells via the AKT and mitogen-activated protein kinase signaling pathways. However, the exact mechanism underlying the effect of HSP20 on the regulation of these signaling pathways remains to be elucidated. To clarify the details of this effect in HCC, we explored the direct targets of HSP20 in HCC using human HCC-derived HuH7 cells with HSP20 overexpression. HSP20 proteins in the HuH7 cells were coimmunoprecipitated with the p85 regulatory subunit and p110 catalytic subunit of phosphoinositide 3-kinase (PI3K), an upstream kinase of AKT. Although HSP20 overexpression in HCC cells failed to affect the expression levels of PI3K, the activity of PI3K in the unstimulated cells and even in the transforming growth factor-alpha stimulated cells were downregulated by HSP20 overexpression. The association of HSP20 with PI3K was also observed in human HCC tissues in vivo. These findings strongly suggest that HSP20 directly associates with PI3K and suppresses its activity in HCC, resulting in the inhibition of the AKT pathway, and subsequently decreasing the growth of HCC. PMID- 24223154 TI - ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury: a longitudinal ecological study. AB - BACKGROUND: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. METHODS AND FINDINGS: English NHS prescribing data for ACE I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540 1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. CONCLUSION: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics. PMID- 24223156 TI - The effect of perspective on presence and space perception. AB - In this paper we report two experiments in which the effect of perspective projection on presence and space perception was investigated. In Experiment 1, participants were asked to score a presence questionnaire when looking at a virtual classroom. We manipulated the vantage point, the viewing mode (binocular versus monocular viewing), the display device/screen size (projector versus TV) and the center of projection. At the end of each session of Experiment 1, participants were asked to set their preferred center of projection such that the image seemed most natural to them. In Experiment 2, participants were asked to draw a floor plan of the virtual classroom. The results show that field of view, viewing mode, the center of projection and display all significantly affect presence and the perceived layout of the virtual environment. We found a significant linear relationship between presence and perceived layout of the virtual classroom, and between the preferred center of projection and perceived layout. The results indicate that the way in which virtual worlds are presented is critical for the level of experienced presence. The results also suggest that people ignore veridicality and they experience a higher level of presence while viewing elongated virtual environments compared to viewing the original intended shape. PMID- 24223155 TI - Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes. AB - Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP), treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of >=2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP) by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p = 3*10(-7), odds ratio = 2, 95% confidence intervals: 1.5-2.6). The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p = 3*10(-9)). Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs. PMID- 24223157 TI - Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension. AB - Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (kappa) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, kappa, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for kappa and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID- 24223158 TI - Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease. AB - The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsons disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. PMID- 24223159 TI - Rapid kill-novel endodontic sealer and Enterococcus faecalis. AB - With growing concern over bacterial resistance, the identification of new antimicrobial means is paramount. In the oral cavity microorganisms are essential to the development of periradicular diseases and are the major causative factors associated with endodontic treatment failure. As quaternary ammonium compounds have the ability to kill a wide array of bacteria through electrostatic interactions with multiple anionic targets on the bacterial surface, it is likely that they can overcome bacterial resistance. Melding these ideas, we investigated the potency of a novel endodontic sealer in limiting Enterococcus faecalis growth. We used a polyethyleneimine scaffold to synthesize nano-sized particles, optimized for incorporation into an epoxy-based endodontic sealer. The novel endodontic sealer was tested for its antimicrobial efficacy and evaluated for biocompatibility and physical eligibility. Our results show that the novel sealer foundation affixes the nanoparticles, achieving surface bactericidal properties, but at the same time impeding nanoparticle penetration into eukaryotic cells and thereby mitigating a possible toxic effect. Moreover, adequate physical properties are maintained. The nanosized quaternary amine particles interact within minutes with bacteria, triggering cell death across wide pH values. Throughout this study we demonstrate a new antibacterial perspective for endodontic sealers; a novel antibacterial, effective and safe antimicrobial means. PMID- 24223160 TI - Roles of the linker region of RNA helicase A in HIV-1 RNA metabolism. AB - RNA helicase A (RHA) promotes multiple steps in HIV-1 production including transcription and translation of viral RNA, annealing of primer tRNA(Lys3) to viral RNA, and elevating the ratio of unspliced to spliced viral RNA. At its amino terminus are two double-stranded RNA binding domains (dsRBDs) that are essential for RHA-viral RNA interaction. Linking the dsRBDs to the core helicase domain is a linker region containing 6 predicted helices. Working in vitro with purified mutant RHAs containing deletions of individual helices reveals that this region may regulate the enzyme's helicase activity, since deletion of helix 2 or 3 reduces the rate of unwinding RNA by RHA. The biological significance of this finding was then examined during HIV-1 production. Deletions in the linker region do not significantly affect either RHA-HIV-1 RNA interaction in vivo or the incorporation of mutant RHAs into progeny virions. While the partial reduction in helicase activity of mutant RHA containing a deletion of helices 2 or 3 does not reduce the ability of RHA to stimulate viral RNA synthesis, the promotion of tRNA(Lys3) annealing to viral RNA is blocked. In contrast, deletion of helices 4 or 5 does not affect the ability of RHA to promote tRNA(Lys3) annealing, but reduces its ability to stimulate viral RNA synthesis. Additionally, RHA stimulation of viral RNA synthesis results in an increased ratio of unspliced to spliced viral RNA, and this increase is not inhibited by deletions in the linker region, nor is the pattern of splicing changed within the ~ 4.0 kb or ~ 1.8 kb HIV-1 RNA classes, suggesting that RHA's effect on suppressing splicing is confined mainly to the first 5'-splice donor site. Overall, the differential responses to the mutations in the linker region of RHA reveal that RHA participates in HIV-1 RNA metabolism by multiple distinct mechanisms. PMID- 24223161 TI - Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel. AB - Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments. PMID- 24223162 TI - Differential responses of hepatic endoplasmic reticulum stress and inflammation in diet-induced obese rats with high-fat diet rich in lard oil or soybean oil. AB - SCOPES: To investigate the effects of high-fat diet enriched with lard oil or soybean oil on liver endoplasmic reticulum (ER) stress and inflammation markers in diet-induced obese (DIO) rats and estimate the influence of following low-fat diet feeding. METHODS AND RESULTS: Male SD rats were fed with standard low-fat diet (LF, n = 10) and two isoenergentic high-fat diets enriched with lard (HL, n = 45) or soybean oil (HS, n = 45) respectively for 10 weeks. Then DIO rats from HL and HS were fed either high-fat diet continuously (HL/HL, HS/HS) or switched to low-fat diet (HL/LF, HS/LF) for another 8 weeks. Rats in control group were maintained with low-fat diet. Body fat, serum insulin level, HOMA-IR and ectopic lipid deposition in liver were increased in HL/HL and HS/HS compared to control, but increased to a greater extent in HL/HL compared to HS/HS. Markers of ER stress including PERK and CHOP protein expression and phosphorylation of eIF2alpha were significantly elevated in HL/HL group while phosphorylation of IRE1alpha and GRP78 protein expression were suppressed in both HL/HL and HS/HS. Besides, inflammatory signals (OPN, TLR2, TLR4 and TNF-alpha) expressions significantly increased in HL/HL compared to others. Switching to low-fat diet reduced liver fat deposition, HOMA-IR, mRNA expression of TLR4, TNF-alpha, PERK in both HL/LF and HS/LF, but only decreased protein expression of OPN, PERK and CHOP in HL/LF group. In addition, HL/LF and HS/LF exhibited decreased phosphorylation of eIF2alpha and increased phosphorylation of IRE1alpha and GRP78 protein expression when compared with HL/HL and HS/HS respectively. CONCLUSIONS: Lard oil was more deleterious in insulin resistance and hepatic steatosis via promoting ER stress and inflammation responses in DIO rats, which may be attributed to the enrichment of saturated fatty acid. Low-fat diet was confirmed to be useful in recovering from impaired insulin sensitivity and liver fat deposition in this study. PMID- 24223163 TI - PDYN rs2281285 variant association with drinking to avoid emotional or somatic discomfort. AB - INTRODUCTION: One of the proposed psychobiological pathways of craving attributes the desire for drinking in the context of tension, discomfort or unpleasant emotions, to "negative" (or "relief") craving. The aim of this study was to replicate a previously reported association of the PDYN rs2281285 variant with negative craving using a different phenotyping approach. METHODS: The TaqMan(r) Genotyping Assay was used to genotype the rs2281285 variant in 417 German alcohol dependent subjects. The presence of negative/relief craving was assessed by asking if participants ever ingested alcohol to avoid unwanted emotional or somatic discomfort. RESULTS: The minor allele of rs2281285 was associated with an increased risk of drinking to avoid/escape unwanted emotional or somatic events (OR=2.29, 95% CI=1.08-4.85, p=0.0298). DISCUSSION: Despite the use of a different phenotyping approach to the measurement of negative craving, our results confirm the association between negative craving and PDYN rs2281285. Genetic markers of negative craving may help to identify subgroups of alcohol-dependent individuals vulnerable to relapse in the context of negative emotions or somatic discomfort, leading to the development of specifically tailored treatment strategies. PMID- 24223164 TI - The FBI1/Akirin2 target gene, BCAM, acts as a suppressive oncogene. AB - Basal cell adhesion molecule (BCAM), known to be a splicing variant of Lutheran glycoprotein (LU), is an immunoglobulin superfamily membrane protein that acts as a laminin alpha5 receptor. The high affinity of BCAM/LU for laminin alpha5 is thought to contribute to the pathogenesis of sickle red blood cells and to various developmental processes. However, the function of BCAM in carcinogenesis is poorly understood. Based on microarray expression analysis, we found that BCAM was one of the target genes of the oncogenic 14-3-3beta-FBI1/Akirin2 complex, which acts as a transcriptional repressor and suppresses MAPK phosphatase-1 gene expression. To elucidate the detailed function of BCAM in malignant tumors, we established BCAM-expressing hepatoma K2 cells. These cells lost the malignant characteristics of parental cells, such as anchorage-independent growth, migration, invasion, and tumorigenicity. Moreover, luciferase reporter assays and chromatin immunoprecipitation analysis revealed that the 14-3-3beta-FBI1/Akirin2 complex bound to the BCAM promoter and repressed transcription. Thus, these data indicate that BCAM is a suppressive oncoprotein, and that FBI1/Akirin2 is involved in tumorigenicity and metastasis of hepatoma through the downregulation of suppressive oncogenes. PMID- 24223165 TI - Nest sanitation as the evolutionary background for egg ejection behaviour and the role of motivation for object removal. AB - Higher interclutch colour variation can evolve under the pressure of brood parasitism to increase the detection of parasitic eggs. Nest sanitation could be a prerequisite for the evolution of anti-parasite defence in terms of egg ejection. In this respect, we used nest sanitation behaviour as a tool to identify: i) motivation and its underlying function and, ii) which features provoke ejection behaviour. Therefore, we experimentally tested whether size, colour or shape may influence ejection behaviour using artificial flat objects. We found a high interclutch variation in egg colouration and egg size in our tree sparrow (Passer montanus) population. Using colour and size we were in fact able to predict clutch affiliation for each egg. Our experiments further revealed the existence of direct anti-parasite behaviours and birds are able to recognise conspecific eggs, since only experimentally-deposited eggs have been removed. Moreover, experiments with different objects revealed that the motivation of tree sparrows to remove experimental objects from their nests was highest during egg laying for objects of varying size, most likely because of parasitism risk at this breeding stage. In contrary, motivation to remove white objects and objects with edges was higher during incubation stage as behavioural patterns connected to hatching started to emerge. The fact that rejection rate of our flat objects was higher than real egg ejection, suggests that egg ejection in tree sparrows and probably more general in small passerines, to be limited by elevated costs to eject eggs with their beaks. The presence of anti-parasite behaviour supports our suggestion that brood parasitism causes variation in egg features, as we have found that tree sparrows can recognise and reject conspecific eggs in their clutch. In conclusion, in tree sparrows it seems that nest sanitation plays a key role in the evolution of the removal of parasitic eggs. PMID- 24223166 TI - Left ventricular mechanics in repaired tetralogy of Fallot with and without pulmonary valve replacement: analysis by three-dimensional speckle tracking echocardiography. AB - BACKGROUND: Altered septal curvature and left ventricular (LV) geometry secondary to right ventricular (RV) dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF) patients. The novel three-dimensional (3D) speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics. METHODS AND RESULTS: Seventy-six patients aged 23.6 +/- 8.3 years, 55 with isolated repair (group I) and 21 with subsequent pulmonary valve replacement (group II), and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. A global performance index was calculated as (global 3D strain*twist gradient)/SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI (all p<0.05). All but the four apical LV segments in patients had reduced regional 3D strain compared with controls (all p<0.05). Septal curvature correlated with LV global 3D strain (r=0.41, p<0.001), average septal strain (r=0.38, p<0.001), twist (r=0.32, p<0.001), twist gradient (r=0.33, p<0.001), and global performance index (r=0.43, p<0.001). CONCLUSIONS: Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement. PMID- 24223167 TI - Depth-dependent differences in community structure of the human colonic microbiota in health. AB - OBJECTIVE: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. DESIGN: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. RESULTS: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. CONCLUSION: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities. PMID- 24223168 TI - Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice. AB - Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS). Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk. PMID- 24223169 TI - Campylobacter jejuni actively invades the amoeba Acanthamoeba polyphaga and survives within non digestive vacuoles. AB - The Gram-negative bacterium Campylobacter jejuni is able to enter, survive and multiply within the free living amoeba Acanthamoeba polyphaga, but the molecular mechanisms behind these events are still unclear. We have studied the uptake and intracellular trafficking of viable and heat killed bacterial cells of the C. jejuni strain 81-176 in A. polyphaga. We found that viable bacteria associated with a substantially higher proportion of Acanthamoeba trophozoites than heat killed bacteria. Furthermore, the kinetics of internalization, the total number of internalized bacteria as well as the intracellular localization of internalized C. jejuni were dramatically influenced by bacterial viability. Viable bacteria were internalized at a high rate already after 1 h of co incubation and were observed in small vacuoles tightly surrounding the bacteria. In contrast, internalization of heat killed C. jejuni was low at early time points and did not peak until 96 h. These cells were gathered in large spacious vacuoles that were part of the degradative pathway as determined by the uptake of fluorescently labeled dextran. The amount of heat killed bacteria internalized by A. polyphaga did never reach the maximal amount of internalized viable bacteria. These results suggest that the uptake and intracellular survival of C. jejuni in A. polyphaga is bacterially induced. PMID- 24223170 TI - Exploratory hydrocarbon drilling impacts to Arctic lake ecosystems. AB - Recent attention regarding the impacts of oil and gas development and exploitation has focused on the unintentional release of hydrocarbons into the environment, whilst the potential negative effects of other possible avenues of environmental contamination are less well documented. In the hydrocarbon-rich and ecologically sensitive Mackenzie Delta region (NT, Canada), saline wastes associated with hydrocarbon exploration have typically been disposed of in drilling sumps (i.e., large pits excavated into the permafrost) that were believed to be a permanent containment solution. However, failure of permafrost as a waste containment medium may cause impacts to lakes in this sensitive environment. Here, we examine the effects of degrading drilling sumps on water quality by combining paleolimnological approaches with the analysis of an extensive present-day water chemistry dataset. This dataset includes lakes believed to have been impacted by saline drilling fluids leaching from drilling sumps, lakes with no visible disturbances, and lakes impacted by significant, naturally occurring permafrost thaw in the form of retrogressive thaw slumps. We show that lakes impacted by compromised drilling sumps have significantly elevated lakewater conductivity levels compared to control sites. Chloride levels are particularly elevated in sump-impacted lakes relative to all other lakes included in the survey. Paleolimnological analyses showed that invertebrate assemblages appear to have responded to the leaching of drilling wastes by a discernible increase in a taxon known to be tolerant of elevated conductivity coincident with the timing of sump construction. This suggests construction and abandonment techniques at, or soon after, sump establishment may result in impacts to downstream aquatic ecosystems. With hydrocarbon development in the north predicted to expand in the coming decades, the use of sumps must be examined in light of the threat of accelerated permafrost thaw, and the potential for these industrial wastes to impact sensitive Arctic ecosystems. PMID- 24223171 TI - Relative mortality among criminals in Norway and the relation to drug and alcohol related offenses. AB - BACKGROUND: Registered offenders are known to have a higher mortality rate, but given the high proportion of offenders with drug-addiction, particularly among offenders with a custodial sentence, higher mortality is expected. While the level of overall mortality compared to the non-criminal population is of interest in itself, we also estimate the risk of death by criminal records related to substance abuse and other types of criminal acts, and separate between those who receive a prison sentence or not. METHODS: Age-adjusted relative risks of death for 2000-2008 were studied in a population based dataset. Our dataset comprise the total Norwegian population of 2.9 million individuals aged 15-69 years old in 1999, of whom 10% had a criminal record in the 1992-1999 period. RESULTS: Individuals with a criminal record have twice the relative risk (RR) of death of the control group (non-offenders). Males with a record of use/possession of drugs and a prison record have an 11.9 RR (females, 15.6); males with a drug record but no prison record have a 6.9 RR (females 10.5). Males imprisoned for driving under the influence of substances have a 4.4 RR (females 5.6); males with a record of driving under the influence but no prison sentence have a 3.2 RR (females 6.5). Other male offenders with a prison record have a 2.8 RR (females 3.7); other male offenders with no prison record have a 1.7 RR (females 2.3). CONCLUSION: Significantly higher mortality was found for people with a criminal record, also for those without any record of drug use. Mortality is much higher for those convicted of substance-related crimes: more so for drug- than for alcohol-related crimes and for women. PMID- 24223172 TI - Organization of multisynaptic inputs to the dorsal and ventral dentate gyrus: retrograde trans-synaptic tracing with rabies virus vector in the rat. AB - Behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. In this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (DG) in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. Three days after the vectors were injected into the dorsal or ventral DG, monosynaptic neuronal labeling was present in the entorhinal cortex, medial septum, diagonal band, and supramammillary nucleus, each of which is known to project to the DG directly. As in previous tracing studies, topographical patterns related to the dorsal and ventral DG were seen in these regions. Five days after infection, more of the neurons in these regions were labeled and labeled neurons were also seen in cortical and subcortical regions, including the piriform and medial prefrontal cortices, the endopiriform nucleus, the claustrum, the cortical amygdala, the medial raphe nucleus, the medial habenular nucleus, the interpeduncular nucleus, and the lateral septum. As in the monosynaptically labeled regions, a topographical distribution of labeled neurons was evident in most of these disynaptically labeled regions. These data indicate that the cortical and subcortical inputs to the dorsal and ventral DG are conveyed through parallel disynaptic pathways. This second-order input difference in the dorsal and ventral DG is likely to contribute to the functional differentiation of the hippocampus along the dorsoventral axis. PMID- 24223173 TI - Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis. AB - Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio) as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 uM 17beta estradiol (E2) or vehicle from 3 hours to 4 days post fertilization (dpf), harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP)). Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen responsive genes identified in male adult zebrafish (Gene Expression Omnibus database). The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific. PMID- 24223174 TI - A genetic polymorphism in pre-miR-27a confers clinical outcome of non-small cell lung cancer in a Chinese population. AB - BACKGROUND: Recent evidence indicates that microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. Our objective was to investigate the association of SNPs in deregulated miRNAs with clinical outcome in patients with non-small cell lung cancer (NSCLC) in a Chinese population. METHODS: Deregulated miRNAs in NSCLC and their SNPs were identified through public databases. A single SNP, rs895819 in pre-miR-27a, was found suitable for selection. TaqMan assays were performed for genotyping and to assess the effect on the overall survival (OS) and chemotherapy response in 576 NSCLC patients. RESULTS: Log-rank test and Cox regression analysis indicated that the G allele of rs895819 was associated with shorter survival and increased risk of death in NSCLC [dominant model: 22.0 vs. 46.0 months, P<0.001; adjusted hazard ratio (HR) = 1.71, 95% confidential interval (CI): 1.12-2.26]. Further stepwise regression analysis suggested that this SNP was an independently unfavorable factor for the prognosis of NSCLC and the effect remained significant in subgroup analysis stratified by clinical parameters and treatment status. Moreover, multivariate logistic regression analysis showed that the subjects with AG/GG genotypes of rs895819 had significantly decreased response rate to platinum-based chemotherapy compared to those with the AA genotype. CONCLUSION: Our results suggest that the pre-miR-27a rs895819 polymorphism may influence NSCLC patients' clinical outcome. Further large sample studies should be used to validate our findings. PMID- 24223175 TI - Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation. AB - We observed in a previous study (PLoS ONE 6:e24522) that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf) with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA) and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC), bilateral dorsomedial prefrontal cortex (DMPFC), bilateral superior frontal gyrus (SFG), and right medial frontopolar cortex (MFPC). Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR) analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA, potentially consistent with the ipsilateral distribution of the monosynaptic projections between these regions. The training is also accompanied by significant increases in the instantaneous (contemporaneous) effects of the left rACC on four other regions - the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our exploratory analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress disorder (PTSD). PMID- 24223176 TI - Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies. AB - The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C), and an RNA hairpin derived from Sendai virus (SeV) Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C) also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk. PMID- 24223177 TI - ADAM17-mediated processing of TNF-alpha expressed by antiviral effector CD8+ T cells is required for severe T-cell-mediated lung injury. AB - Influenza infection in humans evokes a potent CD8(+) T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8(+) T-cell expression of TNF-alpha is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-alpha is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-alpha processing in CD8(+) T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-alpha by CD8(+) T cells significantly attenuated the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. This was due in part to diminished chemokine expression, as TNF-alpha processing was required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. We confirmed the importance of CXCL2 expression in acute lung injury by transferring influenza-specific CD8(+) T cells into transgenic mice lacking CXCR2. These mice exhibited reduced airway infiltration, attenuated lung injury, and enhanced survival. Theses studies describe a critical role for TNF-alpha processing by CD8(+) T cells in the initiation and severity of acute lung injury, which may have important implications for limiting immunopathology during influenza infection and other human infectious or inflammatory diseases. PMID- 24223178 TI - Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis. AB - Leber congenital amaurosis (LCA) is the most severe form of retinal dystrophy with an onset in the first year of life. The most frequent genetic cause of LCA, accounting for up to 15% of all LCA cases in Europe and North-America, is a mutation (c.2991+1655AG) in intron 26 of CEP290. This mutation generates a cryptic splice donor site resulting in the insertion of an aberrant exon (exon X) containing a premature stop codon to CEP290 mRNA. In order to study the pathophysiology of the intronic CEP290 mutation, we generated two humanized knock in mouse models each carrying ~6.3 kb of the human CEP290 gene, either with or without the intronic mutation. Transcriptional characterization of these mouse models revealed an unexpected splice pattern of CEP290 mRNA, especially in the retina. In both models, a new cryptic exon (coined exon Y) was identified in ~5 to 12% of all Cep290 transcripts. This exon Y was expressed in all murine tissues analyzed but not detected in human retina or fibroblasts of LCA patients. In addition, exon x that is characteristic of LCA in humans, was expressed at only very low levels in the retina of the LCA mouse model. Western blot and immunohistochemical analyses did not reveal any differences between the two transgenic models and wild-type mice. Together, our results show clear differences in the recognition of splice sites between mice and humans, and emphasize that care is warranted when generating animal models for human genetic diseases caused by splice mutations. PMID- 24223179 TI - Tyrant dinosaur evolution tracks the rise and fall of Late Cretaceous oceans. AB - The Late Cretaceous (~95-66 million years ago) western North American landmass of Laramidia displayed heightened non-marine vertebrate diversity and intracontinental regionalism relative to other latest Cretaceous Laurasian ecosystems. Processes generating these patterns during this interval remain poorly understood despite their presumed role in the diversification of many clades. Tyrannosauridae, a clade of large-bodied theropod dinosaurs restricted to the Late Cretaceous of Laramidia and Asia, represents an ideal group for investigating Laramidian patterns of evolution. We use new tyrannosaurid discoveries from Utah--including a new taxon which represents the geologically oldest member of the clade--to investigate the evolution and biogeography of Tyrannosauridae. These data suggest a Laramidian origin for Tyrannosauridae, and implicate sea-level related controls in the isolation, diversification, and dispersal of this and many other Late Cretaceous vertebrate clades. PMID- 24223180 TI - Combining stressors that individually impede long-term memory blocks all memory processes. AB - The effects of stress on memory are typically assessed individually; however, in reality different stressors are often experienced simultaneously. Here we determined the effect that two environmentally relevant stressors, crowding and low calcium availability, have on memory and neural activity following operant conditioning of aerial respiration in the pond snail, Lymnaea stagnalis. We measured aerial breathing behaviour and activity of a neuron necessary for memory formation, right pedal dorsal 1 (RPeD1), in the central pattern generator (CPG) that drives aerial respiration in untrained animals, and assessed how these traits changed following training. In naive animals both crowding and combined stressors significantly depressed burst activity in RPeD1 which correlated with a depression in aerial breathing behaviour, whereas low calcium availability had no effect on RPeD1 activity. Following training, changes in burst activity in RPeD1 correlated with behavioural changes, decreasing relative to their naive state at 3 h and 24 h in control conditions when both intermediate-term memory (ITM: 3 h) and long-term memory (LTM: 24 h) are formed, at 3 h but not 24 h when exposed to individual stressors when only ITM is formed, and did not change in combined stressors (i.e. when no memory is formed). Additionally, we also found that Lymnaea formed short-term memory (STM: 10 min) in the presence of individual stressors or under control conditions, but failed to do so in the presence of combined stressors. Our data demonstrate that by combining stressors that individually block LTM only we can block all memory processes. Therefore the effects of two stressors with similar individual affects on memory phenotype may be additive when experienced in combination. PMID- 24223181 TI - A distinct boundary between the higher brain's susceptibility to ischemia and the lower brain's resistance. AB - Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between 'higher' thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na(+)/K(+) pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K(+)]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia. PMID- 24223182 TI - Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. AB - SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment. PMID- 24223183 TI - Monitoring herbivorous fishes as indicators of coral reef resilience in American Samoa. AB - Resilience-based management aims to promote or protect processes and species that underpin an ecosystem's capacity to withstand and recover from disturbance. The management of ecological processes is a developing field that requires reliable indicators that can be monitored over time. Herbivory is a key ecological process on coral reefs, and pooling herbivorous fishes into functional groups based on their feeding mode is increasingly used as it may quantify herbivory in ways that indicate resilience. Here we evaluate whether the biomass estimates of these herbivore functional groups are good predictors of reef benthic assemblages, using data from 240 sites from five island groups in American Samoa. Using an information theoretic approach, we assembled a candidate set of linear and nonlinear models to identify the relations between benthic cover and total herbivore and non-herbivore biomass and the biomass of the aforementioned functional groups. For each benthic substrate type considered (encrusting algae, fleshy macroalgae, hard coral and turf algae), the biomass of herbivorous fishes were important explanatory variables in predicting benthic cover, whereas biomass of all fishes combined generally was not. Also, in all four cases, variation in cover was best explained by the biomass of specific functional groups rather than by all herbivores combined. Specifically: 1) macroalgal and turf algal cover decreased with increasing biomass of 'grazers/detritivores'; and 2) cover of encrusting algae increased with increasing biomass of 'grazers/detritivores' and browsers. Furthermore, hard coral cover increased with the biomass of large excavators/bio-eroders (made up of large-bodied parrotfishes). Collectively, these findings emphasize the link between herbivorous fishes and the benthic community and demonstrate support for the use of functional groups of herbivores as indicators for resilience-based monitoring. PMID- 24223184 TI - Liver lobe volumes and the ratios of liver lobe volumes to spleen volume on magnetic resonance imaging for staging liver fibrosis in a minipig model. AB - OBJECTIVE: To investigate liver lobe volumes and the ratios of liver lobe volumes to spleen volume measured with magnetic resonance imaging (MRI) for quantitatively monitoring and staging liver fibrosis. METHODS: Animal study was approved by Institutional Animal Care and Use Committee. Sixteen minipigs were prospectively used to model liver fibrosis, and underwent abdominal gadolinium enhanced MRI on 0, 5(th), 9(th), 16(th) and 21(st) weekend after modeling this disease staged by biopsy according to METAVIR classification system. On MRI, volume parameters including left lateral liver lobe volume (LLV), left medial liver lobe volume (LMV), right liver lobe volume (RV), caudate lobe volume (CV), and spleen volume (SV) were measured; and LLV/SV, LMV/SV, RV/SV and CV/SV were calculated. Statistical analyses were performed for staging this fibrosis. RESULTS: LLV and CV increased with increasing stage of fibrosis (r = 0.711, 0.526, respectively; all P < 0.05). RV and LMV increased from stage 0 to 2 and decreased from 2 to 4; and RV/SV decreased from 0 to 1, increased from 1 to 2, and decreased from 3 to 4 (all P > 0.05). LLV/SV, LMV/SV and CV/SV decreased from stage 0 to 4 (r = -0.566, -0.748 and -0.620, respectively; all P < 0.05). LLV, CV, LLV/SV, LMV/SV, RV/SV, and CV/SV could distinguish stage 0-1 from 2-4 and 0-2 from 3-4 (all P < 0.05). Among these parameters, LLV and LMV/SV could best classify stage >=2 and >=3, respectively (area under receiver operating characteristic curve = 0.893 and 0.946, respectively). CONCLUSION: LLV and LMV/SV complement each other in staging liver fibrosis, and both parameters should be used to stage this disease. PMID- 24223185 TI - The effects of age and the expression of SPARC on extracellular matrix production by cardiac fibroblasts in 3-D cultures. AB - Fibrillar collagen is the primary component of the cardiac interstitial extracellular matrix. This extracellular matrix undergoes dramatic changes from birth to adulthood and then into advanced age. As evidence, fibrillar collagen content was compared in sections from neonates, adult, and old hearts and was found to increase at each respective age. Cardiac fibroblasts are the principle cell type that produce and control fibrillar collagen content. To determine whether fibroblast production, processing, and deposition of collagen differed with age, primary cardiac fibroblasts from neonate, adult, and old mice were isolated and cultured in 3-dimensional (3D) fibrin gels. Fibroblasts from each age aligned in fibrin gels along points of tension and deposited extracellular matrix. By confocal microscopy, wild-type neonate fibroblasts appeared to deposit less collagen into fibrillar structures than fibroblasts from adults. However, by immunoblot analysis, differences in procollagen production and processing of collagen I were not detected in neonate versus adult fibroblasts. In contrast, fibroblasts from old mice demonstrated increased efficiency of procollagen processing coupled with decreased production of total collagen. SPARC is a collagen-binding protein previously shown to affect cardiac collagen deposition. Accordingly, in the absence of SPARC, less collagen appeared to be associated with fibroblasts of each age grown in fibrin gels. In addition, the increased efficiency of procollagen alpha 1(I) processing in old wild-type fibroblasts was not detected in old SPARC-null fibroblasts. Increased levels of fibronectin were detected in wild-type neonate fibroblasts over that of adult and old fibroblasts but not in SPARC-null neonate fibroblasts versus older ages. Immunostaining of SPARC overlapped with that of collagen I but not to that of fibronectin in 3D cultures. Hence, whereas increases in procollagen processing, influenced by SPARC expression, plausibly contribute to increased collagen deposition in old hearts, other cellular mechanisms likely affect differential collagen deposition by neonate fibroblasts. PMID- 24223186 TI - Estimated glomerular filtration rate and proteinuria are separately and independently associated with the prevalence of atrial fibrillation in general population. AB - BACKGROUND: Both, proteinuria and a decline in glomerular filtration rate (GFR) are associated with greater cardiovascular mortality. However, few studies have explored that proteinuria and lower GFR are related with prevalent atrial fibrillation (AF). METHODS: This cross-sectional study was based on annual health check-up program of community-based population in Gunma, Japan from April 2011 to March 2012. A total of 20,019 adult participants were included. AF was ascertained by a standard 12-lead electrocardiogram. Cross-sectional association and correlates with prevalent AF were examined using multivariable logistic regression analysis. RESULTS: The overall prevalence of AF was 0.6% (2.2 % in participants with eGFR < 60 mL?min(-1)?1.73m(-2), 0.4% and 0.2% in those with eGFR 60 to 89 and ?90 mL?min(-1)?1.73m(-2), p for trend <0.001). The multivariable odds ratio (OR) for AF was 2.86 (95 % CI 1.16 - 7.08, p<0.001) for eGFR< 60 mL?min(-1)?1.73m(-2) versus eGFR? 90 mL?min(-1)?1.73m(-2). This association remained significant with further adjustment for proteinuria. In addition, proteinuria was also strongly associated with increased prevalence of AF (OR 2.96, 95 % CI 1.55-5.68, p<0.001), an association that remained significant after adjustment for eGFR. CONCLUSIONS: Proteinuria and lower eGFR are separately and significantly associated with prevalence of AF independent of well-established risk factors for AF in general population. PMID- 24223187 TI - Mifepristone promotes adiponectin production and improves insulin sensitivity in a mouse model of diet-induced-obesity. AB - The steroid receptor antagonist mifepristone is used as an anti-cancer agent, eliciting both cytostatic and cytotoxic effects on malignant cells. However, the metabolic effects of long-term treatment with mifepristone have remained unclear. The effects of mifepristone on insulin sensitivity and adiponectin secretion were evaluated both in in vivo and in vitro. First, we explored the effects of mifepristone, on metabolic functions in obese mice receiving a high-fat diet. When these mice were fed mifepristone, they exhibited a marked improvement in insulin sensitivity, attenuated hepatic injury, and decreased adipocyte size, compared with mice that received only the high-fat diet. Intriguingly, mifepristone-treated mice showed significantly elevated plasma adiponectin levels. Second, we tested the effects of mifepristone on differentiated 3T3-L1 adipocytes in vitro. When differentiated adipocytes were treated with mifepristone for 48 h, adiponectin was upregulated at both mRNA and protein levels. Collectively, these results reveal novel actions of mifepristone on metabolic functions, in vivo and in vitro, in which the drug exerts antidiabetic effects associated with an upregulation in adiponectin-secretion. PMID- 24223188 TI - Identification and diversity of killer cell Ig-like receptors in Aotus vociferans, a New World monkey. AB - Previous BAC clone analysis of the Platyrrhini owl monkey KIRs have shown an unusual genetic structure in some loci. Therefore, cDNAs encoding KIR molecules from eleven Aotus vociferans monkeys were characterized here; ten putative KIR loci were found, some of which encoded atypical proteins such as KIR4DL and transcripts predicted to encode a D0+D1 configuration (AOTVOKIR2DL1*01v1) which appear to be unique in the Aotus genus. Furthermore, alternative splicing was found as a likely mechanism for producing activator receptors in A. vociferans species. KIR proteins from New World monkeys may be split into three new lineages according to domain by domain phylogenetic analysis. Although the A. vociferans KIR family displayed a high divergence among paralogous genes, individual loci were limited in their genetic polymorphism. Selection analysis showed that both constrained and rapid evolution may operate within the AvKIR family. The frequent alternative splicing (as a likely mechanism generating activator receptors), the presence of KIR4DL and KIR2DL1 (D0+D1) molecules and other data reported here suggest that the KIR family in Aotus has had a rapid evolution, independent from its Catarrhini counterparts. PMID- 24223189 TI - Association of high-density lipoprotein cholesterol with the estimated glomerular filtration rate in a community-based population. AB - BACKGROUND: Reduced kidney function is independently associated with low high density lipoprotein cholesterol (HDL-C) levels in patients with end-stage renal disease (ESRD), those on hemodialysis, and those with stage 3-5 chronic kidney disease (CKD). However, epidemiological data investigating the relationship between HDL-C levels and kidney function in the general population with roughly normal kidney function are limited, and the results are also inconsistent. The aim of this study was to evaluate the relationship between HDL-C levels and the estimated glomerular filtration rate (eGFR) in a community-based population in China. METHODS: This was a community-based cross-sectional survey. In total, 4925 participants (age range, 18-96 years; mean, 51.30+/-11.98 years) were recruited during routine health status examinations. A questionnaire was used to ascertain age, smoking status, and the history of hypertension and diabetes mellitus for each participant. We measured the body mass index, waist circumference, systolic and diastolic blood pressure, and fasting glucose, total cholesterol, triglyceride, HDL-C, low-density lipoprotein cholesterol, uric acid, and serum creatinine level of each participant. eGFR was evaluated using the Chinese modified Modification of Diet in Renal Disease equation. RESULTS: The HDL-C level was higher in the first quartile (lowest quartile) of eGFR than in the fourth quartile (the highest quartile). Additionally, HDL-C levels decreased as eGFR decreased. Pearson's correlation analysis revealed that HDL-C levels were associated with eGFR (r=0.16). After adjustment for some confounders, HDL-C was independently associated with all quartiles of eGFR in the participants. CONCLUSIONS: HDL-C was independently associated with kidney function in a community-dwelling general population. The association between low HDL-C levels and a decreased eGFR gradually strengthened as eGFR declined. PMID- 24223190 TI - A 5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle. AB - Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. Polymorphisms in its promoter and coding regions are likely to impact ZBED6 transcription and growth traits. In this study, rapid amplification of 5' cDNA ends (5'-RACE) analysis revealed two transcription start sites (TSS) for the bovine ZBED6 starting within exon 1 of the ZC3H11A gene (TSS-1) and upstream of the translation start codon of the ZBED6 gene (TSS-2). There was one SNP in the promoter and two missense mutations in the coding region of the bovine ZBED6 by sequencing of the pooled DNA samples (Pool-Seq, n = 100). The promoter and coding region are the key regions for gene function; polymorphisms in these regions can alter gene expression. Quantitative real-time PCR (qPCR) analysis showed that ZBED6 has a broad tissue distribution in cattle and is highly expressed in skeletal muscle. Eleven promoter-detection vectors were constructed, which enabled the cloning of putative promoter sequences and analysis of ZBED6 transcriptional activity by luciferase reporter gene assays. The core region of the basal promoter of bovine ZBED6 is located within region -866 to -556. The activity of WT-826G-pGL3 in driving reporter gene transcription is significantly higher than that of the M-826A-pGL3 construct (P < 0.01). Analysis of gene expression patterns in homozygous full-sibling Chinese Qinchuan cattle showed that the mutant-type Hap-AGG exhibited a lower mRNA level than the wild-type Hap GCA (P < 0.05) in longissimus dorsi muscle (LDM). Moreover, ZBED6 mRNA expression was low in C2C12 cells overexpressing the mutant-type ZBED6 (pcDNA3.1(+)-Hap-GG) (P < 0.01). Our results suggest that the polymorphisms in the promoter and coding regions may modulate the promoter activity and gene expression of bovine ZBED6 in the skeletal muscles of these cattle breeds. PMID- 24223191 TI - Upregulation of miR-135b is involved in the impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients. AB - Previous studies have demonstrated that mesenchymal stem cells from multiple myeloma (MM) patients (MM-hMSCs) display a distinctive gene expression profile, an enhanced production of cytokines and an impaired osteogenic differentiation ability compared to normal donors (ND-hMSCs). However, the underlying molecular mechanisms are unclear. In the present study, we observed that MM-hMSCs exhibited an abnormal upregulation of miR-135b, showing meanwhile an impaired osteogenic differentiation and a decrease of SMAD5 expression, which is the target of miR 135b involved in osteogenesis. By gain and loss of function studies we confirmed that miR-135b negatively regulated hMSCs osteogenesis. We also found that MM cell produced factors stimulated ND-hMSCs to upregulate the expression of miR-135b. Importantly, treatment with a miR-135b inhibitor promoted osteogenic differentiation in MM-hMSCs. Finally, we observed that MM cell-derived soluble factors could induce an upregulation of miR-135b expression in ND-hMSCs in an indirect coculture system and the miR-135b expression turned to normal level after the removal of MM cells. Collectively, we provide evidence that miR-135b is involved in the impaired osteogenic differentiation of MSCs derived from MM patients and might therefore be a promising target for controlling bone disease. PMID- 24223192 TI - Personalized risk assessment of drug-related harm is associated with health outcomes. AB - BACKGROUND: The Independent Scientific Committee on Drugs (ISCD) assigned quantitative scores for harm to 20 drugs. We hypothesized that a personalized, ISCD-based Composite Harm Score (CHS) would be associated with poor health outcomes in polysubstance users. METHODS: A prospective community sample (n=293) of adults living in marginal housing was assessed for substance use. The CHS was calculated based on the ISCD index, and the personal substance use characteristics over four weeks. Regression models estimated the association between CHS and physical, psychological, and social health outcomes. RESULTS: Polysubstance use was pervasive (95.8%), as was multimorbid illness (median 3, possible range 0-12). The median CHS was 2845 (interquartile range 1865-3977). Adjusting for age and sex, every 1000-unit CHS increase was associated with greater mortality (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.07-2.01, p = 0.02), and persistent hepatitis C infection (OR 1.29, 95% CI 1.02-1.67, p = 0.04). The likelihood of substance-induced psychosis increased 1.39-fold (95% CI 1.13-1.67, p = 0.001). The amount spent on drugs increased 1.51-fold (1.40-1.62, p < 0.001) and the odds of having committed a crime increased 1.74-fold (1.46 2.10, p < 0.001). Multimorbid illness increased 1.43-fold (95% CI 1.26-1.63, p < 0.001). CONCLUSIONS: Greater CHS predicts poorer physical, psychological, and social health, and may be a useful quantitative, personalized measure of risk for drug-related harm. PMID- 24223193 TI - Molecular dynamics simulations reveal the HIV-1 Vpu transmembrane protein to form stable pentamers. AB - The human immunodeficiency virus type I (HIV-1) Vpu protein is 81 residues long and has two cytoplasmic and one transmembrane (TM) helical domains. The TM domain oligomerizes to form a monovalent cation selective ion channel and facilitates viral release from host cells. Exactly how many TM domains oligomerize to form the pore is still not understood, with experimental studies indicating the existence of a variety of oligomerization states. In this study, molecular dynamics (MD) simulations were performed to investigate the propensity of the Vpu TM domain to exist in tetrameric, pentameric, and hexameric forms. Starting with an idealized alpha-helical representation of the TM domain, a thorough search for the possible orientations of the monomer units within each oligomeric form was carried out using replica-exchange MD simulations in an implicit membrane environment. Extensive simulations in a fully hydrated lipid bilayer environment on representative structures obtained from the above approach showed the pentamer to be the most stable oligomeric state, with interhelical van der Waals interactions being critical for stability of the pentamer. Atomic details of the factors responsible for stable pentamer structures are presented. The structural features of the pentamer models are consistent with existing experimental information on the ion channel activity, existence of a kink around the Ile17, and the location of tetherin binding residues. Ser23 is proposed to play an important role in ion channel activity of Vpu and possibly in virus propagation. PMID- 24223194 TI - Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis. AB - INTRODUCTION: Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA. METHODS: In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses. RESULTS: All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee. CONCLUSIONS: Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms. PMID- 24223195 TI - A common copy number variation (CNV) polymorphism in the CNTNAP4 gene: association with aging in females. AB - BACKGROUND: Aging is a biological process strongly determined by genetics. However, only a few single nucleotide polymorphisms (SNPs) have been reported to be consistently associated with aging. While investigating whether copy number variations (CNVs) could fill this gap, we focused on CNVs that have not been studied in previous SNP-based searches via tagging SNPs. METHODS: TaqMan qPCR assays were developed to quantify 20 common CNVs in 222 senior American Caucasians in order to reveal possible association with longevity. The replication study was comprised of 1283 community-dwelling senior European Caucasians. Replicated CNVs were further investigated for association with healthy aging and aging-related diseases, while association with longevity was additionally tested in Caenorhabditis elegans. RESULTS: In the discovery study of >=80 vs.<80 years old seniors, a homozygous intronic CNV deletion in the CNTNAP4 gene was inversely associated with survival to the age of 80 (OR=0.51, 95%CI 0.29 0.87, p=0.015 before correction for multiple testing). After stratification by sex, association remained significant in females (OR=0.41, 95%CI 0.21-0.77, p=0.007), but not in males (OR=0.97, 95%CI 0.33-2.79, p=1). The finding was validated in a replication study (OR=0.66, 95%CI 0.48-0.90, p=0.011 for females). CNTNAP4 association with longevity was supported by a marked 25% lifespan change in C. elegans after knocking down the ortholog gene. An inverse association of the CNV del/del variant with female healthy aging was observed (OR=0.39, 95%CI 0.19-0.76, p=0.006). A corresponding positive association with aging-related diseases was revealed for cognitive impairment (OR=2.17, 95%CI 1.11-4.22, p=0.024) and, in independent studies, for Alzheimer's (OR=4.07, 95%CI 1.17-14.14, p=0.036) and Parkinson's (OR=1.59, 95%CI 1.03-2.42, p=0.041) diseases. CONCLUSION: This is the first demonstration for association of the CNTNAP4 gene and one of its intronic CNV polymorphisms with aging. Association with particular aging-related diseases awaits replication and independent validation. PMID- 24223196 TI - Protective role of AMP-activated protein kinase-evoked autophagy on an in vitro model of ischemia/reperfusion-induced renal tubular cell injury. AB - Ischemia/reperfusion (I/R) injury is a common cause of injury to target organs such as brain, heart, and kidneys. Renal injury from I/R, which may occur in renal transplantation, surgery, trauma, or sepsis, is known to be an important cause of acute kidney injury. The detailed molecular mechanism of renal I/R injury is still not fully clear. Here, we investigate the role of AMP-activated protein kinase (AMPK)-evoked autophagy in the renal proximal tubular cell death in an in vitro I/R injury model. To mimic in vivo renal I/R injury, LLC-PK1 cells, a renal tubular cell line derived from pig kidney, were treated with antimycin A and 2-deoxyglucose to mimic ischemia injury followed by reperfusion with growth medium. This I/R injury model markedly induced apoptosis and autophagy in LLC-PK1 cells in a time-dependent manner. Autophagy inhibitor 3 methyladenine (3MA) significantly enhanced I/R injury-induced apoptosis. I/R could also up-regulate the phosphorylation of AMPK and down-regulate the phosphorylation of mammalian target of rapamycin (mTOR). Cells transfected with small hairpin RNA (shRNA) for AMPK significantly increased the phosphorylation of mTOR as well as decreased the induction of autophagy followed by enhancing cell apoptosis during I/R. Moreover, the mTOR inhibitor RAD001 significantly enhanced autophagy and attenuated cell apoptosis during I/R. Taken together, these findings suggest that autophagy induction protects renal tubular cell injury via an AMPK-regulated mTOR pathway in an in vitro I/R injury model. AMPK-evoked autophagy may be as a potential target for therapeutic intervention in I/R renal injury. PMID- 24223197 TI - Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures. AB - BACKGROUND: Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects. PRINCIPAL FINDINGS: In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+) suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment. PMID- 24223198 TI - Factors associated with depressive symptoms among Filipino university students. AB - Depression can be prevented if its symptoms are addressed early and effectively. Prevention against depression among university students is rare in the Philippines, but is urgent because of the rising rates of suicide among the group. Evidence is needed to systematically identify and assist students with higher levels of depressive symptoms. We carried out a survey to determine the social and demographic factors associated with higher levels of depressive symptoms among 2,436 Filipino university students. The University Students Depression Inventory with measures on lethargy, cognition-emotion, and academic motivation, was used. Six of the 11 factors analyzed were found to be statistically significantly associated with more intense levels of depressive symptoms. These factors were: frequency of smoking, frequency of drinking, not living with biological parents, dissatisfaction with one's financial condition, level of closeness with parents, and level of closeness with peers. Sex, age category, course category, year level and religion were not significantly related. In identifying students with greater risk for depression, characteristics related to lifestyle, financial condition, parents and peers are crucial. There is a need to carry out more surveys to develop the pool of local knowledge on student depression. PMID- 24223199 TI - Association of HDL-related loci with age-related macular degeneration and plasma lutein and zeaxanthin: the Alienor study. AB - BACKGROUND: Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations. METHODS: Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1). RESULTS: After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45 1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance. CONCLUSION: These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin. PMID- 24223200 TI - Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma. AB - Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL) showed differential expression of Ran GTPase activating protein 1 (RanGAP1) between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50) were RanGAP1(+), while reactive lymphoid hyperplasia (n = 12) was RanGAP1(+) predominantly in germinal centers. RanGAP1 was also highly expressed in other B cell lymphomas (BCL, n = 180) with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95%) or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%). Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 +/- 2.28 ng/mL, n = 62) than in low-grade BCL (0.75 +/- 2.12 ng/mL, n = 52) and healthy controls (0.55 +/- 1.58 ng/mL, n = 75) (high-grade BCL vs. low-grade BCL, p = 0.002; high grade BCL vs. control, p < 0.001, Mann-Whitney U test). In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035) and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030) along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon), a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL. PMID- 24223201 TI - A genome-wide association study points out the causal implication of SOX9 in the sex-reversal phenotype in XX pigs. AB - Among farm animals, pigs are known to show XX sex-reversal. In such cases the individuals are genetically female but exhibit a hermaphroditism, or a male phenotype. While the frequency of this congenital disease is quite low (less than 1%), the economic losses are significant for pig breeders. These losses result from sterility, urogenital infections and the carcasses being downgraded because of the risk of boar taint. It has been clearly demonstrated that the SRY gene is not involved in most cases of sex-reversal in pigs, and that autosomal recessive mutations remain to be discovered. A whole-genome scan analysis was performed in the French Large-White population to identify candidate genes: 38 families comprising the two non-affected parents and 1 to 11 sex-reversed full-sib piglets were genotyped with the PorcineSNP60 BeadChip. A Transmission Disequilibrium Test revealed a highly significant candidate region on SSC12 (most significant p value<4.65.10(-10)) containing the SOX9 gene. SOX9, one of the master genes involved in testis differentiation, was sequenced together with one of its main regulatory region Tesco. However, no causal mutations could be identified in either of the two sequenced regions. Further haplotype analyses did not identify a shared homozygous segment between the affected pigs, suggesting either a lack of power due to the SNP properties of the chip, or a second causative locus. Together with information from humans and mice, this study in pigs adds to the field of knowledge, which will lead to characterization of novel molecular mechanisms regulating sexual differentiation and dysregulation in cases of sex reversal. PMID- 24223203 TI - WHO antiretroviral therapy guidelines 2010 and impact of tenofovir on chronic kidney disease in Vietnamese HIV-infected patients. AB - OBJECTIVE: The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country. DESIGN: Cross sectional study was performed. METHODS: Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD. RESULTS: Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD. CONCLUSIONS: Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients. PMID- 24223202 TI - Endothelium-dependent relaxation and angiotensin II sensitivity in experimental preeclampsia. AB - OBJECTIVE: We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat. METHODS: Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine-mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N(G)-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR. RESULTS: The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non pregnant rats. These changes were not observed during preeclampsia. CONCLUSION: Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation. PMID- 24223204 TI - Intratibial injection of human multiple myeloma cells in NOD/SCID IL 2Rgamma(null) mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies. AB - BACKGROUND: We systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents. DESIGN AND METHODS: Using flow cytometry and near infrared fluorescence in-vivo imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rgamma(null) mice (NSG). RESULTS: Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or alphaCD122-treated NOD/SCID). Comparison of NSG and alphaCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses. CONCLUSIONS: Our results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies. PMID- 24223205 TI - Disconcordance in statistical models of bisphenol A and chronic disease outcomes in NHANES 2003-08. AB - BACKGROUND: Bisphenol A (BPA), a high production chemical commonly found in plastics, has drawn great attention from researchers due to the substance's potential toxicity. Using data from three National Health and Nutrition Examination Survey (NHANES) cycles, we explored the consistency and robustness of BPA's reported effects on coronary heart disease and diabetes. METHODS AND FINDINGS: We report the use of three different statistical models in the analysis of BPA: (1) logistic regression, (2) log-linear regression, and (3) dose-response logistic regression. In each variation, confounders were added in six blocks to account for demographics, urinary creatinine, source of BPA exposure, healthy behaviours, and phthalate exposure. Results were sensitive to the variations in functional form of our statistical models, but no single model yielded consistent results across NHANES cycles. Reported ORs were also found to be sensitive to inclusion/exclusion criteria. Further, observed effects, which were most pronounced in NHANES 2003-04, could not be explained away by confounding. CONCLUSIONS: Limitations in the NHANES data and a poor understanding of the mode of action of BPA have made it difficult to develop informative statistical models. Given the sensitivity of effect estimates to functional form, researchers should report results using multiple specifications with different assumptions about BPA measurement, thus allowing for the identification of potential discrepancies in the data. PMID- 24223206 TI - A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kappaB signaling in chordoma biology. AB - Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R gamma-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IkappaB, as well as inhibition of an NF-kappaB gene expression signature demonstrated the importance of NF-kappaB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing. PMID- 24223207 TI - Growth and airborne transmission of cell-sorted life cycle stages of Pneumocystis carinii. AB - Pneumocystis organisms are airborne opportunistic pathogens that cannot be continuously grown in culture. Consequently, the follow-up of Pneumocystis stage to-stage differentiation, the sequence of their multiplication processes as well as formal identification of the transmitted form have remained elusive. The successful high-speed cell sorting of trophic and cystic forms is paving the way for the elucidation of the complex Pneumocystis life cycle. The growth of each sorted Pneumocystis stage population was followed up independently both in nude rats and in vitro. In addition, by setting up a novel nude rat model, we attempted to delineate which cystic and/or trophic forms can be naturally aerially transmitted from host to host. The results showed that in axenic culture, cystic forms can differentiate into trophic forms, whereas trophic forms are unable to evolve into cystic forms. In contrast, nude rats inoculated with pure trophic forms are able to produce cystic forms and vice versa. Transmission experiments indicated that 12 h of contact between seeder and recipient nude rats was sufficient for cystic forms to be aerially transmitted. In conclusion, trophic- to cystic-form transition is a key step in the proliferation of Pneumocystis microfungi because the cystic forms (but not the trophic forms) can be transmitted by aerial route from host to host. PMID- 24223208 TI - Activation of IFN-gamma/STAT/IRF-1 in hepatic responses to Klebsiella pneumoniae infection. AB - BACKGROUND: Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. METHODOLOGY/PRINCIPLE FINDINGS: Auto bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naive control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naive mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-gamma production was significantly evoked in the liver. To mediate IFN-gamma signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor) 1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1beta and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2alpha, were exclusively revealed in the K. pneumoniae-infected diabetic mice. CONCLUSION: The activation of IFN gamma/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN gamma for mediating the hepatic response to K. pneumoniae infection. PMID- 24223209 TI - Malaria infection has spatial, temporal, and spatiotemporal heterogeneity in unstable malaria transmission areas in northwest Ethiopia. AB - BACKGROUND: Malaria elimination requires successful nationwide control efforts. Detecting the spatiotemporal distribution and mapping high-risk areas are useful to effectively target pockets of malaria endemic regions for interventions. OBJECTIVE: The aim of the study was to identify patterns of malaria distribution by space and time in unstable malaria transmission areas in northwest Ethiopia. METHODS: Data were retrieved from the monthly reports stored in the district malaria offices for the period between 2003 and 2012. Eighteen districts in the highland and fringe malaria areas were included and geo-coded for the purpose of this study. The spatial data were created in ArcGIS10 for each district. The Poisson model was used by applying Kulldorff methods using the SaTScanTM software to analyze the purely temporal, spatial and space-time clusters of malaria at a district levels. RESULTS: The study revealed that malaria case distribution has spatial, temporal, and spatiotemporal heterogeneity in unstable transmission areas. Most likely spatial malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR =197764.1, p<0.001). Significant spatiotemporal malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR=197764.1, p<0.001) between 2003/1/1 and 2012/12/31. A temporal scan statistics identified two high risk periods from 2009/1/1 to 2010/12/31 (LLR=72490.5, p<0.001) and from 2003/1/1 to 2005/12/31 (LLR=26988.7, p<0.001). CONCLUSION: In unstable malaria transmission areas, detecting and considering the spatiotemporal heterogeneity would be useful to strengthen malaria control efforts and ultimately achieve elimination. PMID- 24223210 TI - Intrinsic features in microRNA transcriptomes link porcine visceral rather than subcutaneous adipose tissues to metabolic risk. AB - MicroRNAs (miRNAs) are non-coding small RNA ~22 nucleotides in length that can regulate the expression of a wide range of coding genes at the post transcriptional level. Visceral adipose tissues (VATs) and subcutaneous adipose tissues (SATs), the two main fat compartments in mammals, are anatomically, physiologically, metabolically, and clinically distinct. Various studies of adipose tissues have focused mainly on DNA methylation, and mRNA and protein expression, nonetheless little research sheds directly light on the miRNA transcriptome differences between these two distinct adipose tissue types. Here, we present a comprehensive investigation of miRNA transcriptomes across six variant porcine adipose tissues by small RNA-sequencing. We identified 219 known porcine miRNAs, 97 novel miRNA*s, and 124 miRNAs that are conserved to other mammals. A set of universally abundant miRNAs (i.e., miR-148a-3p, miR-143-3p, miR 27b-3p, miR-let-7a-1-5p, and miR-let-7f-5p) across the distinct adipose tissues was found. This set of miRNAs may play important housekeeping roles that are involved in adipogenesis. Clustering analysis indicated significant variations in miRNA expression between the VATs and SATs, and highlighted the role of the greater omentum in responding to potential metabolic risk because of the observed enrichment in this tissue of the immune- and inflammation-related miRNAs, such as the members of miR-17-92 cluster and miR-181 family. Differential expression of the miRNAs between the VATs and SATs, and miRNA target prediction analysis revealed that the VATs-specific enriched miRNAs were associated mainly with immune and inflammation responses. In summary, the differences of miRNA expression between the VATs and SATs revealed some of their intrinsic differences and indicated that the VATs might be closely associated with increased risk of metabolic disorders. PMID- 24223211 TI - Exploring the binding nature of pyrrolidine pocket-dependent interactions in the polo-box domain of polo-like kinase 1. AB - BACKGROUND: Over the years, a great deal of effort has been focused on the design and synthesis of potent, linear peptide inhibitors targeting the polo-like kinase 1 (Plk1), which is critically involved in multiple mitotic processes and has been established as an adverse prognostic marker for tumor patients. Plk1 localizes to its intracellular anchoring sites via its polo-box domain, and inhibiting the Plk1 polo-box domain has been considered as an approach to circumvent the specificity problems associated with inhibiting the conserved adenosine triphosphate-binding pocket. The polo-box domain consists of two different binding regions, such as the unique, broader pyrrolidine-binding pocket and the conserved, narrow, Tyr-rich hydrophobic channel, among the three Plk polo-box domains (Plks 1-3), respectively. Therefore, the studies that provide insights into the binding nature of the unique, broader pyrrolidine-binding pocket might lead to the development of selective Plk1-inhibitory compounds. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to retain the monospecificity by targeting the unique, broader pyrrolidine-binding pocket, here, for the first time, a systematic approach was undertaken to examine the structure-activity relationship of N-terminal-truncated PLHSpTM derivatives, to apply a site directed ligand approach using bulky aromatic and non-aromatic systems, and to characterize the binding nature of these analogues using X-ray crystallographic studies. We have identified a new mode of binding interactions, having improved binding affinity and retaining the Plk1 polo-box domain specificity, at the pyrrolidine-binding pocket. Furthermore, our data revealed that the pyrrolidine binding pocket was very specific to recognize a short and bulky hydrophobic ligand like adamantane, whereas the Tyr-rich hydrophobic channel was specific with lengthy and small hydrophobic groups. CONCLUSION/SIGNIFICANCE: The progress made using our site-directed ligands validated this approach to specifically direct the ligand into the unique pyrrolidine-binding region, and it extends the applicability of the strategy for discovering selective protein-protein interaction inhibitors. PMID- 24223212 TI - Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. AB - Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 +/- 0.3 (mean +/- SD), range 2.8-4.2, and the average total lactate was 1.0% +/- 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid. PMID- 24223213 TI - Inhibitory role of the small leucine-rich proteoglycan biglycan in bladder cancer. AB - BACKGROUND: Urothelial bladder cancer is the ninth most common cancer. Despite surgical and chemotherapeutic treatment the prognosis is still poor once bladder cancer progresses to a muscle-invasive state. Discovery of new diagnostic markers and pathophysiologic effectors might help to contribute to novel diagnostic and therapeutic options. The extracellular matrix microenvironment shaped by the extracellular matrix critically affects tumor cell and stroma cell functions. Therefore, aim of the present study was to assess the possible implication of the small leucine-rich proteoglycan biglycan in progression of human urothelial bladder cancer. METHODS AND RESULTS: For this purpose tumor biopsies of 76 bladder cancer patients with different tumor stages (pTa, pT1-T4) were investigated with respect to biglycan expression and correlated with a long-term (10 years) clinical follow-up. Interestingly, higher biglycan mRNA expression was associated with higher tumor stages and muscle invasiveness. In vitro knock-down of endogenous biglycan in human urothelial carcinoma cells (J82 cells) increased proliferation, whereas addition of recombinant biglycan and overexpression of biglycan inhibited tumor cell proliferation. In line with this growth-inhibitory effect of biglycan, transplantation of J82 cells after knock-down of biglycan resulted in significantly increased growth of subcutaneous xenograft tumors in nude mice in vivo. Furthermore, treatment with two anti-proliferative, multi receptor tyrosine kinase inhibitors-sunitinib and sorafenib-strongly upregulated biglycan expression. Collectively, the experimental data suggest that high biglycan expression is associated with reduced tumor cell proliferation. In accordance, Kaplan-Meier analysis revealed higher 10-year survival in patients with high biglycan mRNA expression in tumor biopsies. CONCLUSION: In conclusion, the present data suggest that biglycan is an endogenous inhibitor of bladder cancer cell proliferation that is upregulated in response to anti-proliferative tyrosine kinase inhibitors. In addition, high biglycan expression is associated with favorable prognosis. PMID- 24223214 TI - Bone marrow deficiency of MCPIP1 results in severe multi-organ inflammation but diminishes atherogenesis in hyperlipidemic mice. AB - OBJECTIVE: MCPIP1 is a newly identified protein that profoundly impacts immunity and inflammation. We aim to test if MCPIP1 deficiency in hematopoietic cells results in systemic inflammation and accelerates atherogenesis in mice. APPROACH AND RESULTS: After lethally irradiated, LDLR(-/-) mice were transplanted with bone marrow cells from either wild-type or MCPIP1(-/-) mice. These chimeric mice were fed a western-type diet for 7 weeks. We found that bone marrow MCPIP1(-/-) mice displayed a phenotype similar to that of whole body MCPIP1(-/-) mice, with severe systemic and multi-organ inflammation. However, MCPIP1(-/-) bone marrow recipients developed >10-fold less atherosclerotic lesions in the proximal aorta than WT bone marrow recipients, and essentially no lesions in en face aorta. The diminishment in atherosclerosis in bone marrow MCPIP1(-/-) mice may be partially attributed to the slight decrease in their plasma lipids. Flow cytometric analysis of splenocytes showed that bone marrow MCPIP1(-/-) mice contained reduced numbers of T cells and B cells, but increased numbers of regulatory T cells, Th17 cells, CD11b+/Gr1+ cells and CD11b+/Ly6C(low) cells. This overall anti-atherogenic leukocyte profile may also contribute to the reduced atherogenesis. We also examined the cholesterol efflux capability of MCPIP1 deficient macrophages, and found that MCPIP1 deficiency increased cholesterol efflux to apoAI and HDL, due to increased protein levels of ABCA1 and ABCG1. CONCLUSIONS: Hematopoietic deficiency of MCPIP1 resulted in severe systemic and multi-organ inflammation but paradoxically diminished atherogenesis in mice. The reduced atheroegensis may be explained by the decreased plasma cholesterol levels, the anti-atherogenic leukocyte profile, as well as enhanced cholesterol efflux capability. This study suggests that, while atherosclerosis is a chronic inflammatory disease, the mechanisms underlying atherogenesis-associated inflammation in arterial wall versus the inflammation in solid organs may be substantially different. PMID- 24223215 TI - Ecosystem-service tradeoffs associated with switching from annual to perennial energy crops in riparian zones of the US Midwest. AB - Integration of energy crops into agricultural landscapes could promote sustainability if they are placed in ways that foster multiple ecosystem services and mitigate ecosystem disservices from existing crops. We conducted a modeling study to investigate how replacing annual energy crops with perennial energy crops along Wisconsin waterways could affect a variety of provisioning and regulating ecosystem services. We found that a switch from continuous corn production to perennial-grass production decreased annual income provisioning by 75%, although it increased annual energy provisioning by 33%, decreased annual phosphorous loading to surface water by 29%, increased below-ground carbon sequestration by 30%, decreased annual nitrous oxide emissions by 84%, increased an index of pollinator abundance by an average of 11%, and increased an index of biocontrol potential by an average of 6%. We expressed the tradeoffs between income provisioning and other ecosystem services as benefit-cost ratios. Benefit cost ratios averaged 12.06 GJ of additional net energy, 0.84 kg of avoided phosphorus pollution, 18.97 Mg of sequestered carbon, and 1.99 kg of avoided nitrous oxide emissions for every $1,000 reduction in income. These ratios varied spatially, from 2- to 70-fold depending on the ecosystem service. Benefit-cost ratios for different ecosystem services were generally correlated within watersheds, suggesting the presence of hotspots--watersheds where increases in multiple ecosystem services would come at lower-than-average opportunity costs. When assessing the monetary value of ecosystem services relative to existing conservation programs and environmental markets, the overall value of enhanced services associated with adoption of perennial energy crops was far lower than the opportunity cost. However, when we monitized services using estimates for the social costs of pollution, the value of enhanced services far exceeded the opportunity cost. This disparity between recoverable costs and social value represents a fundamental challenge to expansion of perennial energy crops and sustainable agricultural landscapes. PMID- 24223216 TI - Common duckweed (Lemna minor) is a versatile high-throughput infection model for the Burkholderia cepacia complex and other pathogenic bacteria. AB - Members of the Burkholderia cepacia complex (Bcc) have emerged in recent decades as problematic pulmonary pathogens of cystic fibrosis (CF) patients, with severe infections progressing to acute necrotizing pneumonia and sepsis. This study presents evidence that Lemna minor (Common duckweed) is useful as a plant model for the Bcc infectious process, and has potential as a model system for bacterial pathogenesis in general. To investigate the relationship between Bcc virulence in duckweed and Galleria mellonella (Greater wax moth) larvae, a previously established Bcc infection model, a duckweed survival assay was developed and used to determine LD50 values. A strong correlation (R(2) = 0.81) was found between the strains' virulence ranks in the two infection models, suggesting conserved pathways in these vastly different hosts. To broaden the application of the duckweed model, enteropathogenic Escherichia coli (EPEC) and five isogenic mutants with previously established LD50 values in the larval model were tested against duckweed, and a strong correlation (R(2) = 0.93) was found between their raw LD50 values. Potential virulence factors in B. cenocepacia K56-2 were identified using a high-throughput screen against single duckweed plants. In addition to the previously characterized antifungal compound (AFC) cluster genes, several uncharacterized genes were discovered including a novel lysR regulator, a histidine biosynthesis gene hisG, and a gene located near the gene encoding the recently characterized virulence factor SuhB(Bc). Finally, to demonstrate the utility of this model in therapeutic applications, duckweed was rescued from Bcc infection by treating with bacteriophage at 6-h intervals. It was observed that phage application became ineffective at a timepoint that coincided with a sharp increase in bacterial invasion of plant tissue. These results indicate that common duckweed can serve as an effective infection model for the investigation of bacterial virulence factors and therapeutic strategies to combat them. PMID- 24223217 TI - Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults. AB - BACKGROUND: There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability. OBJECTIVE: The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults. MATERIALS AND METHODS: The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohort), which is a part of The Korean Genome Epidemiology Study (KoGES). A total of 5,532 subjects (2,116 men and 3,416 women) aged 40 years and older were recruited from rural communities in South Korea between 2005 and 2010. Phytate:zinc molar ratio, estimated from a food-based food frequency questionnaire (FFQ) of 106 food items, was used to determine zinc bioavailability, and carotid intima media thickness (cIMT) and pulse wave velocity (PWV) were measured to calculate the subclinical atherosclerotic index. RESULTS: We found that phytate:zinc molar ratio is positively related to cIMT in men. A higher phytate:zinc molar ratio was significantly related to an increased risk of atherosclerosis in men, defined as the 80(th) percentile value of cIMT (5(th) vs. 1(st) quintile, OR = 2.11, 95% CI 1.42-3.15, P for trend = 0.0009), and especially in elderly men (5(th) vs. 1(st) quintile, OR = 2.58, 95% CI 1.52 4.37, P for trend = 0.0021). We found a positive relationship between phytate:zinc molar ratio and atherosclerosis risk among women aged 65 years or younger. Phytate:zinc molar ratio was not found to be related to PWV. CONCLUSIONS: Lower zinc bioavailability may be related to higher atherosclerosis risk. PMID- 24223218 TI - Mathematically derived body volume and risk of musculoskeletal pain among housewives in North India. AB - BACKGROUND: Global Burden of Disease Study 2010 demonstrates the impact of musculoskeletal diseases as the second greatest cause of disability globally in all regions of the world. The study was conducted to determine the role of mathematically derived body volume (BV), body volume index (BVI), body mass index (BMI), body surface area (BSA) and body fat % (BF %) on musculoskeletal pain (MSP) among housewives in National Capital Region (NCR). METHODS: A cross sectional study was undertaken among 495 housewives from Gurgaon and New Okhla Industrial Development Area (NOIDA) in National Capital Region (NCR), New Delhi, India. The study includes questionnaire survey, clinical examination and body composition monitoring among housewives. RESULTS: A significantly higher BMI, BVI, BV and BSA were observed in subjects with MSP as compared to those who had no MSP. This was also true for subjects with pain in knee for BMI category for overweight. Subjects with pain in limbs had significantly high BMI and BVI as compared to subjects with no MSP. A significant positive correlation of age with BMI, BVI, BV and BSA was observed among subjects having no MSP denoting a direct relationship of age and these body factors. CONCLUSIONS: The prevalence of MSP among housewives is associated with increasing age, BMI and BVI. This can possibly be used for formulating a strategy for prevention of MSP. PMID- 24223219 TI - A controlled approach to the emotional dilution of the Stroop effect. AB - We re-examined a modified emotional Stroop task that included an additional colour-word alongside the emotional word, providing the response conflict of the traditional Stroop task. Negative emotionally salient (i.e. unpleasant') words are claimed to capture attention, producing a smaller Stroop effect for negative words compared to neutral words; this phenomenon is called the emotional dilution of the Stroop effect. To address previous limitations, this study compared negative words with lexically matched neutral words in a powered sample of 45 participants. Results demonstrated an emotional Stroop effect (slower colour naming responses for negative words) and a traditional Stroop effect but not an emotional dilution of the Stroop effect. This finding is at odds with claims that other processing resources are diminished through the failure to disengage attention from emotional information. No matter how attention towards emotional information builds up over time, our findings indicate that attentional resources are not fully captured by negative words. PMID- 24223220 TI - Thirst perception and osmoregulation of vasopressin secretion are altered during recovery from septic shock. AB - OBJECTIVE: Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. DESIGN: Prospective interventional study. SETTING: Intensive care unit (ICU) at Raymond Poincare and Etampes Hospitals. PATIENTS: Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. INTERVENTION: Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes. MEASUREMENTS AND MAIN RESULTS: Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. CONCLUSION: More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated. PMID- 24223221 TI - Identification of genomic regions regulating Pax6 expression in embryonic forebrain using YAC reporter transgenic mouse lines. AB - The transcription factor Pax6 is a crucial regulator of eye and central nervous system development. Both the spatiotemporal patterns and the precise levels of Pax6 expression are subject to tight control, mediated by an extensive set of cis regulatory elements. Previous studies have shown that a YAC reporter transgene containing 420 Kb of genomic DNA spanning the human PAX6 locus drives expression of a tau-tagged GFP reporter in mice in a pattern that closely resembles that of endogenous Pax6. Here we have closely compared the pattern of tau-GFP reporter expression at the cellular level in the forebrains and eyes of transgenic mice carrying either complete or truncated versions of the YAC reporter transgene with endogenous Pax6 expression and found several areas where expression of tau-GFP and Pax6 diverge. Some discrepancies are due to differences between the intracellular localization or perdurance of tau-GFP and Pax6 proteins, while others are likely to be a consequence of transcriptional differences. We show that cis-regulatory elements that lie outside the 420 kb fragment of PAX6 are required for correct expression around the pallial-subpallial boundary, in the amygdala and the prethalamus. Further, we found that the YAC reporter transgene effectively labels cells that contribute to the lateral cortical stream, including cells that arise from the pallium and subpallium, and therefore represents a useful tool for studying lateral cortical stream migration. PMID- 24223222 TI - Identification of novel markers that demarcate the nucleolus during severe stress and chemotherapeutic treatment. AB - The nucleolus, the ribosomal factory of the cell, has emerged as a key player that regulates many aspects of cell biology. Several thousand proteins associate at least transiently with nucleoli, thereby generating a highly dynamic compartment with a protein profile which is sensitive to changes in cell physiology and pharmacological agents. Powerful tools that reliably demarcate the nucleoli are a prerequisite to measure their composition and activities. Previously, we developed quantitative methods to measure fluorescently labeled molecules in nucleoli. While these tools identify nucleoli under control and mild stress conditions, the accurate detection of nucleolar boundaries under harsh experimental conditions is complicated by the lack of appropriate markers for the nucleolar compartment. Using fluorescence microscopy we have now identified new marker proteins to detect nucleoli upon (a) severe stress and (b) drug treatments that trigger a pronounced reorganization of nucleoli. Our results demonstrate that nucleolin is an ideal marker to delimit nucleoli when cells are exposed to heat or oxidative stress. Furthermore, we show for the first time that cellular apoptosis susceptibility protein (CAS) and human antigen R protein (HuR) are excluded from nucleoli and can be employed to delimit these compartments under severe conditions that redistribute major nucleolar proteins. As proof-of principle, we used these markers to demarcate nucleoli in cells treated with pharmacological compounds that disrupt the nucleolar organization. Furthermore, to gain new insights into the biology of the nucleolus, we applied our protocols and quantified stress- and drug-induced changes in nucleolar organization and function. Finally, we show that CAS, HuR and nucleolin not only identify nucleoli in optical sections, but are also suitable to demarcate the nucleolar border following 3D reconstruction. Taken together, our studies present novel marker proteins that delimit nucleoli with high confidence under a variety of experimental settings. PMID- 24223223 TI - Experimental manipulation of melanism demonstrates the plasticity of preferred temperature in an agricultural pest (Phaulacridium vittatum). AB - Phenotypic plasticity is a key trait of successful pest species, and may increase the ability to cope with higher, more variable temperatures under climate change. We investigate the plasticity of preferred temperature in a widespread agricultural pest, the wingless grasshopper (Phaulacridium vittatum). Preferred temperature is a measure of thermoregulatory behaviour through habitat selection. It is influenced by melanism, which affects body temperature by determining the amount of radiation absorbed by the body. First we demonstrate that body temperature and preferred temperature in P. vittatum is influenced by melanism, by comparing the preferred temperature of the colour morphs in laboratory thermal gradients and field body temperatures in natural populations. We then test whether preferred temperature changes in response to changes in body temperature, by determining preferred temperature before and after manipulation of melanism by painting. When melanism was manipulated experimentally in live grasshoppers, preferred temperature changed to reflect the thermal qualities of the new colour. The preferred temperature of light grasshoppers increased after they were painted black, and decreased after being painted white. Similarly, dark individuals that were painted white behaved like a light individual, maintaining a lower body temperature. Preferred temperature in P.vittatum is a plastic thermoregulatory response to ambient temperature, mediated by the influence of melanism on body temperature. PMID- 24223224 TI - Family history as a predictor for disease risk in healthy individuals: a cross sectional study in Slovenia. AB - BACKGROUND: Family history can be used as a genetic risk predictor for common non communicable diseases. The aim of this study was to determine the prevalence of healthy individuals at risk of developing these diseases, based on their self reported family history. METHODS AND FINDINGS: This was a cross-sectional observational study. Data were collected in the three largest occupational practices in primary health care centres in Slovenia, a Central European country. The study population consisted of consecutive individuals who came to occupational practices for their regular preventive check-up from November 2010 to June 2012. We included 1,696 individuals. Data were collected by a self developed questionnaire. The main outcome was the number of participants at a moderate or high risk for the development of cardiovascular diseases, diabetes, and cancer. The final sample consisted of 1,340 respondents. Moderate or high risk for the development of cardiovascular diseases was present in 280 (20.9%) participants, for the development of diabetes in 154 (11.5%) participants and for cancer in 163 (12.1%) participants. CONCLUSIONS: In this study, we found a significant proportion of healthy individuals with an increased genetic risk for common non-communicable diseases; consequently further genetic and clinical evaluation and preventive measures should be offered. PMID- 24223225 TI - Immunomodulatory activity of a novel, synthetic beta-glucan (beta-glu6) in murine macrophages and human peripheral blood mononuclear cells. AB - Natural beta-glucans extracted from plants and fungi have been used in clinical therapies since the late 20th century. However, the heterogeneity of natural beta glucans limits their clinical applicability. We have synthesized beta-glu6, which is an analog of the lentinan basic unit, beta-(1->6)-branched beta-(1->3) glucohexaose, that contains an alpha-(1->3)-linked bond. We have demonstrated the stimulatory effect of this molecule on the immune response, but the mechanisms by which beta-glu6 activates innate immunity have not been elucidated. In this study, murine macrophages and human PBMCs were used to evaluate the immunomodulatory effects of beta-glu6. We showed that beta-glu6 activated ERK and c-Raf phosphorylation but suppressed the AKT signaling pathway in murine macrophages. Additionally, beta-glu6 enhanced the secretion of large levels of cytokines and chemokines, including CD54, IL-1alpha, IL-1beta, IL-16, IL-17, IL 23, IFN-gamma, CCL1, CCL3, CCL4, CCL12, CXCL10, tissue inhibitor of metalloproteinase-1 (TIMP-1) and G-CSF in murine macrophages as well as IL-6, CCL2, CCL3, CCL5, CXCL1 and macrophage migration inhibitory factor (MIF) in human PBMCs. In summary, it demonstrates the immunomodulatory activity of beta-glu6 in innate immunity. PMID- 24223226 TI - Branched-chain amino acids enhance premature senescence through mammalian target of rapamycin complex I-mediated upregulation of p21 protein. AB - Branched-chain amino acids (BCAAs) have been applied as an oral supplementation to patients with liver cirrhosis. BCAAs not only improve nutritional status of patients but also decrease the incidence of liver cancer. Mammalian target of rapamycin (mTOR) links cellular metabolism with growth and proliferation in response to nutrients, energy, and growth factors. BCAAs, especially leucine, have been shown to regulate protein synthesis through mTOR activities. On the other hand, cellular senescence is suggested to function as tumor suppressor mechanisms, and induced by a variety of stimuli including DNA damage-inducing drugs. However, it is not clear how BCAA supplementation prevents the incidence of liver cancer in patients with cirrhosis. Here we showed that human cancer cells, HepG2 and U2OS, cultured in medium containing BCAAs with Fischer's ratio about 3, which was shown to have highest activities to synthesize and secrete of albumin, had higher activities to induce premature senescence and elevate mTORC1 activities. Furthermore, BCAAs themselves enhanced the execution of premature senescence induced by DNA damage-inducing drugs, which was effectively prevented by rapamycin. These results strongly suggested the contribution of the mTORC1 pathway to the regulation of premature senescence. Interestingly, the protein levels of p21, a p53 target and well-known gene essential for the execution of cellular senescence, were upregulated in the presence of BCAAs. These results suggested that BCAAs possibly contribute to tumor suppression by enhancing cellular senescence mediated through the mTOR signalling pathway. PMID- 24223227 TI - Determining the binding affinity of therapeutic monoclonal antibodies towards their native unpurified antigens in human serum. AB - Monoclonal antibodies (mAbs) are a growing segment of therapeutics, yet their in vitro characterization remains challenging. While it is essential that a therapeutic mAb recognizes the native, physiologically occurring epitope, the generation and selection of mAbs often rely on the use of purified recombinant versions of the antigen that may display non-native epitopes. Here, we present a method to measure both, the binding affinity of a therapeutic mAb towards its native unpurified antigen in human serum, and the antigen's endogenous concentration, by combining the kinetic exclusion assay and Biacore's calibration free concentration analysis. To illustrate the broad utility of our method, we studied a panel of mAbs raised against three disparate soluble antigens that are abundant in the serum of healthy donors: proprotein convertase subtilisin/kexin type 9 (PCSK9), progranulin (PGRN), and fatty acid binding protein (FABP4). We also determined the affinity of each mAb towards its purified recombinant antigen and assessed whether the interactions were pH-dependent. Of the six mAbs studied, three did not appear to discriminate between the serum and recombinant forms of the antigen; one mAb bound serum antigen with a higher affinity than recombinant antigen; and two mAbs displayed a different affinity for serum antigen that could be explained by a pH-dependent interaction. Our results highlight the importance of taking pH into account when measuring the affinities of mAbs towards their serum antigens, since the pH of serum samples becomes increasingly alkaline upon aerobic handling. PMID- 24223228 TI - Utility of host delivered RNAi of two FMRF amide like peptides, flp-14 and flp 18, for the management of root knot nematode, Meloidogyne incognita. AB - Root knot nematode, Meloidogyne incognita, is an obligate sedentary endoparasite that infects a large number of crop species and causes substantial yield losses. Non-chemical based control strategies for these nematodes are gaining importance. In the present study, we have demonstrated the significance of two FMRFamide like peptide genes (flp-14 and flp-18) for infection and development of resistance to M. incognita through host-derived RNAi. The study demonstrated both in vitro and in planta validation of RNAi-induced silencing of the two genes cloned from J2 stage of M. incognita. In vitro silencing of both the genes interfered with nematode migration towards the host roots and subsequent invasion into the roots. Transgenic tobacco lines were developed with RNAi constructs of flp-14 and flp-18 and evaluated against M. incognita. The transformed plants did not show any visible phenotypic variations suggesting the absence of any off-target effects. Bioefficacy studies with deliberate challenging of M. incognita resulted in 50 80% reduction in infection and multiplication confirming the silencing effect. We have provided evidence for in vitro and in planta silencing of the genes by expression analysis using qRT-PCR. Thus the identified genes and the strategy can be used as a potential tool for the control of M. incognita. This is the first ever report that has revealed the utility of host delivered RNAi of flps to control M. incognita. The strategy can also be extended to other crops and nematodes. PMID- 24223229 TI - Does social isolation and low societal participation predict disability pension? A population based study. AB - PURPOSE: The aim was to examine the potential influence of social isolation and low societal participation on the future risk of receiving disability pension among individuals in Sweden. A specific aim was to describe differences depending on disability pension diagnoses, and how the results were modified by sex and age. METHOD: The study comprised representative samples of Swedish women and men, who had been interviewed in any of the annual Swedish Surveys of Living Conditions between 1990 and 2007. Information on disability pension and diagnoses was added from the Swedish Social Insurance Agency's database (1991-2011). The mean number of years of follow-up for the 53920 women and men was twelve years (SD 5.5), and the study base was restricted to the ages 20 to 64 years of age. The predictors were related to disability pension by Cox's proportional hazards regression. RESULTS: Social isolation and low societal participation were associated with future disability pension also after control for age, year of interview, socio demographic conditions and self reported longstanding illness. Lone individuals were at increased risk of disability pension, and the effect of living without children was modified by sex and age. An increase in risk was particularly noticeable among younger women who reported that they had sparse contacts with others, and no close friend. Both women and men who reported that they did not participate in political discussions and who could not appeal on a decision by a public authority were also at increased risk. The effects of social isolation were mainly attributed to disability pension with mental diagnoses, and to younger individuals. CONCLUSIONS: The study suggests that social isolation and low societal participation are predictors of future disability pension. Social isolation and low societal participation increased particularly the risk of future disability pension in mental diagnoses among younger individuals. PMID- 24223230 TI - Seeing it from both sides: do approaches to involving patients in improving their safety risk damaging the trust between patients and healthcare professionals? An interview study. AB - OBJECTIVE: Encouraging patients to be more vigilant about their care challenges the traditional dynamics of patient-healthcare professional interactions. This study aimed to explore, from the perspectives of both patients and frontline healthcare staff, the potential consequences of patient-mediated intervention as a way of pushing safety improvement through the involvement of patients. DESIGN: Qualitative study, using purposive sampling and semi-structured interviews with patients, their relatives and healthcare professionals. Emergent themes were identified using grounded theory, with data coded using NVIVO 8. PARTICIPANTS: 16 patients, 4 relatives, (mean age (sd) 60 years (15); 12 female, 8 male) and 39 healthcare professionals, (9 pharmacists, 11 doctors, 12 nurses, 7 health care assistants). SETTING: Participants were sampled from general medical and surgical wards, taking acute and elective admissions, in two hospitals in north east England. RESULTS: Positive consequences were identified but some actions encouraged by current patient-mediated approaches elicited feelings of suspicion and mistrust. For example, patients felt speaking up might appear rude or disrespectful, were concerned about upsetting staff and worried that their care might be compromised. Staff, whilst apparently welcoming patient questions, appeared uncertain about patients' motives for questioning and believed that patients who asked many questions and/or who wrote things down were preparing to complain. Behavioural implications were identified that could serve to exacerbate patient safety problems (e.g. staff avoiding contact with inquisitive patients or relatives; patients avoiding contact with unreceptive staff). CONCLUSIONS: Approaches that aim to push improvement in patient safety through the involvement of patients could engender mistrust and create negative tensions in the patient provider relationship. A more collaborative approach, that encourages patients and healthcare staff to work together, is needed. Future initiatives should aim to shift the current focus away from "checking up" on individual healthcare professionals to one that engages both parties in the common goal of enhancing safety. PMID- 24223231 TI - Predictors of diabetic foot and leg ulcers in a developing country with a rapid increase in the prevalence of diabetes mellitus. AB - OBJECTIVE: To identify the socio demographic, life style and foot examination related predictors of diabetic foot and leg ulcers with a view to develop a screening tool appropriate for the use in an outpatient setting. RESEARCH DESIGN AND METHODS: This cross sectional study included type 2 diabetes mellitus (DM) patients; 88 subjects with leg and foot ulcers and 80 non ulcer controls. Socio demographic data and life style factors were documented. Foot was examined for skin changes and structural abnormalities. Distal peripheral neuropathy was assessed by pressure sense, vibration sense and joint position sense. Multivariate analysis by logistic regression was used to determine the significant predictors in screening for foot ulcers. RESULTS: Education of grade 6 and below (OR--1.41, 95% CI; 1.03-4.68), low income (OR--23.3, 95% CI; 1.5 34.0), impaired vibration sense (OR--24.79, 95% CI; 9.3-66.2), abnormal monofilament test on first (OR--1.69, 95% CI; 1.36-16.6), third (OR--3.4, 95% CI; 1.1-10.6) and fifth (OR--1.8, 95% CI; 1.61-12.6) toes are found to be predictors of increased risk whereas incidental diagnosis of DM (OR--0.03, 95% CI; 0.003 0.28), wearing covered shoes (OR--0.003, 95% CI; 0.00-0.28), presence of normal skin color (OR--0.01, 95% CI; 0.001-0.14) and normal monofilament test on first metatarsal head (OR--0.10, 95% CI; 0.00-0.67) are protective factors for ulcers. CONCLUSIONS: Ten independent risk and protective factors identified in this study are proposed as a simple screening tool to predict the risk of developing leg and foot ulcers in patients with DM. PMID- 24223232 TI - Application of a hybrid model for predicting the incidence of tuberculosis in Hubei, China. AB - BACKGROUND: A prediction model for tuberculosis incidence is needed in China which may be used as a decision-supportive tool for planning health interventions and allocating health resources. METHODS: The autoregressive integrated moving average (ARIMA) model was first constructed with the data of tuberculosis report rate in Hubei Province from Jan 2004 to Dec 2011.The data from Jan 2012 to Jun 2012 were used to validate the model. Then the generalized regression neural network (GRNN)-ARIMA combination model was established based on the constructed ARIMA model. Finally, the fitting and prediction accuracy of the two models was evaluated. RESULTS: A total of 465,960 cases were reported between Jan 2004 and Dec 2011 in Hubei Province. The report rate of tuberculosis was highest in 2005 (119.932 per 100,000 population) and lowest in 2010 (84.724 per 100,000 population). The time series of tuberculosis report rate show a gradual secular decline and a striking seasonal variation. The ARIMA (2, 1, 0) * (0, 1, 1)12 model was selected from several plausible ARIMA models. The residual mean square error of the GRNN-ARIMA model and ARIMA model were 0.4467 and 0.6521 in training part, and 0.0958 and 0.1133 in validation part, respectively. The mean absolute error and mean absolute percentage error of the hybrid model were also less than the ARIMA model. DISCUSSION AND CONCLUSIONS: The gradual decline in tuberculosis report rate may be attributed to the effect of intensive measures on tuberculosis. The striking seasonal variation may have resulted from several factors. We suppose that a delay in the surveillance system may also have contributed to the variation. According to the fitting and prediction accuracy, the hybrid model outperforms the traditional ARIMA model, which may facilitate the allocation of health resources in China. PMID- 24223233 TI - Identifying cardiac syncope based on clinical history: a literature-based model tested in four independent datasets. AB - BACKGROUND: We aimed to develop and test a literature-based model for symptoms that associate with cardiac causes of syncope. METHODS AND RESULTS: Seven studies (the derivation sample) reporting >=2 predictors of cardiac syncope were identified (4 Italian, 1 Swiss, 1 Canadian, and 1 from the United States). From these, 10 criteria were identified as diagnostic predictors. The conditional probability of each predictor was calculated by summation of the reported frequencies. A model of conditional probabilities and a priori probabilities of cardiac syncope was constructed. The model was tested in four datasets of patients with syncope (the test sample) from Calgary (n=670; 21% had cardiac syncope), Amsterdam (n=503; 9%), Milan (n=689; 5%) and Rochester (3877; 11%). In the derivation sample ten variables were significantly associated with cardiac syncope: age, gender, structural heart disease, low number of spells, brief or absent prodrome, supine syncope, effort syncope, and absence of nausea, diaphoresis and blurred vision. Fitting the test datasets to the full model gave C-statistics of 0.87 (Calgary), 0.84 (Amsterdam), 0.72 (Milan) and 0.71 (Rochester). Model sensitivity and specificity were 92% and 68% for Calgary, 86% and 67% for Amsterdam, 76% and 59% for Milan, and 73% and 52% for Rochester. A model with 5 variables (age, gender, structural heart disease, low number of spells, and lack of prodromal symptoms) was as accurate as the total set. CONCLUSION: A simple literature-based Bayesian model of historical criteria can distinguish patients with cardiac syncope from other patients with syncope with moderate accuracy. PMID- 24223234 TI - Atypical presentation of an advanced obstructive biliary cancer without jaundice. AB - PATIENT: Female, 60 FINAL DIAGNOSIS: Cholangiocarcinoma Symptoms: Abdominal pain * abdominal discomfort MEDICATION: - Clinical Procedure: - Specialty: Oncology. OBJECTIVE: Unusual natural history/clinical course. BACKGROUND: Cholangiocarcinoma remains to be a challenging case to diagnose and manage as it usually presents in advanced stage and survival rate remains dismal despite the medical breakthroughs. It is usually classified as intrahepatic, perihilar or distal tumor which can lead to bile duct obstruction causing sluggish flow of bile through the biliary tract and promoting increased absorption of bilirubin, bile acids and bile salts into systemic circulation accounting for the occurrence of jaundice, dark-colored urine and generalized pruritus. It usually becomes symptomatic when the tumor has significantly obstructed the biliary drainage causing painless jaundice and deranged liver function with cholestatic pattern. Jaundice occurs in 90% of the cases when the tumor has obstructed the biliary drainage system. A markedly dilated gallbladder as initial presenting feature in the absence of other typical obstructive clinical manifestations of an advanced stage of the cholangiocarcinoma is rare. CASE REPORT: This case report presents an atypical case of an elderly woman who presented with advanced metastatic ductal cholangiocarcinoma with markedly dilated gallbladder and liver mass without other clinical manifestations and laboratory evidence of cholestatic jaundice. CONCLUSIONS: The mere presence of Courvoisier's sign, even in the absence of other signs of biliary obstruction, could be suggestive of advanced neoplastic process along the biliary tract. Laboratory evidence of cholestasis might lag behind the clinical severity of the biliary obstruction in cholangiocarcinoma. PMID- 24223235 TI - Neuroprotective effects of a variety of pomegranate juice extracts against MPTP induced cytotoxicity and oxidative stress in human primary neurons. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely used in vitro models to investigate the pathophysiology of Parkinson's disease (PD) and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamadh against MPTP induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD(+) and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD(+), ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular. PMID- 24223237 TI - Potent Vinblastine C20' Ureas Displaying Additionally Improved Activity Against a Vinblastine-Resistant Cancer Cell Line. AB - A series of disubstituted C20'-urea derivatives of vinblastine were prepared from 20'-aminovinblastine that was made accessible through a unique Fe(III)/NaBH4- mediated alkene functionalization reaction of anhydrovinblastine. Three analogs were examined across a panel of 15 human tumor cell lines, displaying remarkably potent cell growth inhibition activity (avg. IC50 = 200-300 pM), being 10-200 fold more potent than vinblastine (avg. IC50 = 6.1 nM). Significantly, the analogs also display further improved activity against the vinblastine-resistant HCT116/VM46 cell line that bears the clinically relevant overexpression of Pgp, exhibiting IC50 values on par with that of vinblastine against the sensitive HCT116 cell line, 100-200-fold greater than the activity of vinblastine against the resistant HCT116/VM46 cell line, and display a reduced 10-20-fold activity differential between the matched sensitive and resistant cell lines (vs 100-fold for vinblastine). PMID- 24223238 TI - Students' perception of the learning environment at Xavier University School of Medicine, Aruba. AB - PURPOSE: The learning environment at Xavier University School of Medicine (XUSOM), Aruba has not been previously studied. Hence, the present study was carried out using the Dundee Ready Education Environment Measure (DREEM) to obtain student perceptions about the learning environment and compare the same among different subgroups of respondents. METHODS: The questionnaire was administered to undergraduate medical students in their first to fifth semester during the first two weeks of June 2013. The students' perceptions were evaluated by noting their degree of agreement with a set of 50 statements using a Likert type scale. The mean overall score and the scores of subcategory were calculated and compared among different respondents (P<0.05). RESULTS: Seventy-three of the 86 students (84.9%) completed the questionnaire. The overall mean+/-SD score was 131.79+/-22.86 (maximum score 200). The mean+/-SD score for students' perception of teaching/learning was 31.99+/-6.23 (maximum score, 48), while the score for students' perceptions of teachers was 30.05+/-5.54 (maximum score, 44). The mean+/-SD scores for students' academic self-perception, students' perception of the atmosphere, and students' social self-perception were 21.88+/-5.11 (maximum score, 32), 30.92+/-8.59 (maximum score, 48), and 16.96+/-4.71 (maximum score, 28), respectively. There were no differences in scores according to the respondents' personal characteristics. CONCLUSION: The student responses about the learning environment at the institution were positive. We plan to obtain regular student feedback as the curriculum becomes progressively more student centered and integrated. PMID- 24223236 TI - Effects of resveratrol on vitrified porcine oocytes. AB - Vitrified MII porcine oocytes are characterized by reduced developmental competence, associated with the activation of the apoptotic pathway. Resveratrol (R), a polyphenolic compound present in several vegetal sources, has been reported to exert, among all its other biological effects, an antiapoptotic one. The aim of this study was to determine the effects of R (2 uM) on the apoptotic status of porcine oocytes vitrified by Cryotop method, evaluating phosphatidylserine (PS) exteriorization and caspases activation. R was added during IVM (A); 2 h postwarming incubation (B); vitrification/warming and 2 h postwarming incubation (C); all previous phases (D). Data on PS exteriorization showed, in each treated group, a significantly higher (P < 0.05) percentage of live nonapoptotic oocytes as compared with CTR; moreover, the percentage of live apoptotic oocytes was significantly (P < 0.05) lower in all R-treated groups relative to CTR. The results on caspase activation showed a tendency to an increase of viable oocytes with inactive caspases in B, C, and D, while a significant (P < 0.05) increase in A compared to CTR was recorded. These data demonstrate that R supplementation in various phases of IVM and vitrification/warming procedure can modulate the apoptotic process, improving the resistance of porcine oocytes to cryopreservation-induced damage. PMID- 24223239 TI - Ethics in Scientific Publication: Plagiarism and other Scientific Misconduct. PMID- 24223240 TI - Library collaboration with medical humanities in an american medical college in qatar. AB - The medical humanities, a cross-disciplinary field of practice and research that includes medicine, literature, art, history, philosophy, and sociology, is being increasingly incorporated into medical school curricula internationally. Medical humanities courses in Writing, Literature, Medical Ethics and History can teach physicians-in-training communication skills, doctor-patient relations, and medical ethics, as well as empathy and cross-cultural understanding. In addition to providing educational breadth and variety, the medical humanities can also play a practical role in teaching critical/analytical skills. These skills are utilized in differential diagnosis and problem-based learning, as well as in developing written and oral communications. Communication skills are a required medical competency for passing medical board exams in the U.S., Canada, the UK and elsewhere. The medical library is an integral part of medical humanities training efforts. This contribution provides a case study of the Distributed eLibrary at the Weill Cornell Medical College in Qatar in Doha, and its collaboration with the Writing Program in the Premedical Program to teach and develop the medical humanities. Programs and initiatives of the DeLib library include: developing an information literacy course, course guides for specific courses, the 100 Classic Books Project, collection development of 'doctors' stories' related to the practice of medicine (including medically-oriented movies and TV programs), and workshops to teach the analytical and critical thinking skills that form the basis of humanistic approaches to knowledge. This paper outlines a 'best practices' approach to developing the medical humanities in collaboration among the medical library, faculty and administrative stakeholders. PMID- 24223241 TI - Evaluating the Relationship between Body Size and Body Shape with the Risk of Breast Cancer. AB - OBJECTIVE: This study aims to determine the relationship between body size and body shape with the risk of breast cancer. METHODS: In this case control study, 480 women participated (240 women with breast cancer in case group and 240 healthy women in control group). After completing the interview form, the weight, height, waist circumference, hip circumference and breast size, were measured. The data were analyzed using statistical test by SPSS11.5. RESULTS: The present study showed that the mean of hip circumference were significantly different in both groups (p=0.036). The size of the breast was statistically significant between the two groups. Thyroid type, one of the body shapes, was more seen in the case group than control group (p<0.001). CONCLUSION: This study revealed that the risk of breast cancer increases with increased hip circumference. In addition, the results indicate that body shape may be a useful predictor in determining the risk of breast cancer. More studies should be designed to address this subject. PMID- 24223242 TI - Psychological Predictors of Intention to Deliver Vaginally through the Extended Parallel Process Model: A Mixed-Method Approach in Pregnant Iranian Women. AB - OBJECTIVES: Despite the fact that cesarean delivery does not offer significant health benefits for either mother or newborn, there has been a noticeable upward trend in elective cesarean births in Iran, over the last two decades. This study aims to examine whether knowledge, perception of health threats, efficacy, and personal beliefs act as psychological predictors towards the intention of women to have a normal vaginal delivery. METHODS: The mixed-method approach was used as quantitative and qualitative design. Simultaneously, 290 pregnant women who visited prenatal clinics participated in the study. Quantitative and qualitative data were collected using a structured questionnaire based on Witte's Extended Parallel Process Model, and four focus groups, respectively. RESULTS: Women perceived lower personal risk but higher levels of efficacy. Perceived self efficacy, severity, and response efficacy emerged as significant predictors of intention to experience vaginal birth. The participants' insufficient knowledge and misconceptions about birth methods were prevalent. Major themes were identified and divided into negative and positive beliefs about vaginal birth. CONCLUSION: This educational model is useful for understanding women's intention to undergo a vaginal birth, especially when it is combined with a qualitative approach. Maternal care providers should acknowledge their clients' beliefs and intended childbirth methods prior to offering medical intervention. PMID- 24223243 TI - Maternal child abuse and its association with maternal anxiety in the socio cultural context of iran. AB - OBJECTIVES: The prevalence of parental violence has been an area of major public concern. There are few available data detailing the ways parents and other caregivers discipline children, particularly in low and middle income countries. This study focuses on the prevalence of different types of maternal child abuse and its association with maternal anxiety in the socio-cultural context of Iran. METHODS: Participants in this cross-sectional study consisted of 562 mothers with the last child aged from 1 month to 12 years old who attended the Amirkola Children's Referral Hospital in Mazandaran Province, Iran, seeking healthcare services for their children. Demographic characteristics of the mothers, their children and reactions to conflicts with children were evaluated by a validated version of Conflict Tactics Scale for Parent and Child. Also, the relationship between maternal anxiety and child abuse was assessed using the Spielberger State Trait Anxiety Inventory. The association between variables was examined by Pearson correlation coefficient, independent t-test, one-way ANOVA, and multivariate regression. RESULTS: The prevalence of mother-to-child corporal punishment, severe physical abuse and very severe physical abuse were 436 (78%), 260 (46%) and 180 (32%), respectively. Verbal emotional abuse was reported by 506 (90%) participants and nonverbal emotional abuse was reported in 374 (67%) cases. A correlation was observed between child abuse and mothers' age (p=0.02), as well as with the number of children in the family (p=0.03), and the mothers' trait anxiety (p<0.001). CONCLUSION: Overall, the assessment of maternal child abuse should be an important focus for evaluation in mothers with anxiety and vice versa, when child abuse is suspected, maternal psychological assessment should be essential. PMID- 24223244 TI - Evaluation of the sensitivity and specificity of immunohistochemical markers in the differential diagnosis of effusion cytology. AB - OBJECTIVE: To evaluate the sensitivity and specificity of Calretinin and Carcinoembryonic antigen as immunocytochemical markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in effusion cytology. METHODS: This study included 50 patients who presented with effusions (26 pleural and 24 peritoneal), at Al-Kadhimya Teaching Hospital who were selected according to their preliminary diagnosis from 1st December 2010 to 30th June 2011. Effusion fluids were aspirated and processed for both conventional cytological methods using Papanicolaou-stain and immunocytochemical staining with anti Calretinin and Carcinoembryonic antigen. RESULTS: The sensitivity of cytology for detection of malignant cells was 77%, with 100% specificity and 86% accuracy. Calretinin was observed to be a specific (100%) and sensitive (90%) marker for mesothelial cells (of benign etiology). Carcinoembryonic antigen exhibited 70% sensitivity and 100% specificity for adenocarcinoma cells. When the results of both cytology and immunocytochemistry were considered in conjunction, the sensitivity for the detection of malignancy increased to 97%, with 100% specificity and 98% accuracy. CONCLUSION: Calretinin and Carcinoembryonic antigen were found to be useful markers for differentiating reactive mesothelial cells from metastatic adenocarcinoma cells in smears prepared from body fluids. Also, the combination of both cytology and immunocytochemical studies using the two markers can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions. PMID- 24223245 TI - The diagnostic efficacy of adenosine deaminase in tubercular effusion. AB - OBJECTIVE: This study aims to evaluate the diagnostic efficacy of adenosine deaminase in tubercular effusions. METHODS: This study was conducted at the Department of General Medicine and Cardiovascular and Thoracic Surgery, SKIMS, for a period of two years between November 2008 and November 2010. A total of 57 patients presenting with pleural effusions during the two-year study period, who presented with clinical manifestations suggestive of tuberculosis (i.e., the presence of productive cough, low-grade fever, night sweats, weight loss, and chest pain, especially if these symptoms last (3)4 weeks) were included in the study. If the patients presented with less than two of these symptoms, and especially if the clinical manifestations were of <4 weeks duration, they were excluded from the study. RESULTS: The mean adenosine deaminase activity level in all the 57 patients was 109 U/L while the mean adenosine deaminase activity levels in pleural TB patients was 80 U/, and 64 U/L in the controls (p=0.381). Considering 40 U/L as the cut off, the results were positive in 35 out of 39 tuberculosis patients and 9 out of 18 controls. The sensitivity of adenosine deaminase for tubercular effusions worked out to be 90%, with only 50% specificity. CONCLUSION: This study suggests that the estimation of adenosine deaminase activity in pleural fluid is a rapid diagnostic tool for differentiation of tubercular and non tubercular-effusions. The sensitivity and specificity of adenosine deaminase for tubercular effusions in this study was 90% and 50% respectively. PMID- 24223246 TI - The patterns and causes of neonatal mortality at a tertiary hospital in oman. AB - OBJECTIVE: To report the patterns and causes of neonatal death from a tertiary care neonatal intensive care unit over a period of four years. METHODS: This is a retrospective cohort study where four years data (January 2006 - December 2009) of all inborn neonatal admissions and deaths were collected from the neonatal intensive care unit at Sultan Qaboos University hospital on predesigned forms. All out born admissions and deaths were excluded. The causes of neonatal death were classified using Wigglesworth's classification. RESULTS: The number of inborn live births during the study period was 10064 and the total number of inborn neonatal admissions was 1475. The total deaths (neonatal and post neonatal) at the neonatal intensive care unit was 73 (63 inborn and 10 out born). Among the inborn, five deaths were post neonatal deaths and hence, excluded from analysis. Among the remaining inborn neonatal deaths (n=58), 34 (59%) were males and 24 (41%) were females. The number of neonatal admissions increased over the years during the study period from 248 to 356, while the number of deaths also increased from 10 deaths in 2006, to 20 deaths in 2009. The primary causes of neonatal deaths were prematurity and its complications 52% (n=30). Lethal congenital malformations lead to 17 (29%) newborn deaths, specific diagnosis in 7 newborns (12%), and birth asphyxia in four (7%) of cases. CONCLUSION: There was an increasing trend of neonatal admissions and deaths among inborn babies. Prematurity, with sepsis as its major complication and congenital malformations were the leading cause of neonatal mortality. PMID- 24223247 TI - Diagnosis of adult chronic rhinosinusitis: can nasal endoscopy predict intrasinus disease? AB - OBJECTIVES: To define the role of endoscopic evaluation of middle meatus in adult patients clinically diagnosed to have chronic rhino-sinusitis and its ability to predict intra-sinus mucosal involvement as compared to CT scan. METHODS: This prospective analytical study was conducted on consecutive patients with diagnosis of chronic rhino-sinusitis who were symptomatic and fulfilled the American Academy of Otolaryngology - Head and Neck Surgery Task Force criteria. The patients were enrolled prospectively and were subjected to rigid diagnostic nasal endoscopy and classified as defined by the revised Sinus Allergy Health Partnership Task Force criteria. The patients then underwent non contrast CT sinuses on the same day. Results were analyzed as a diagnostic test evaluation using CT as a gold standard. RESULTS: Among the 75 study patients with symptom based chronic rhino-sinusitis, nasal endoscopy was abnormal in 65 patients (87%). Of these patients, 60/65 (92%) showed positive findings on CT scan. Ten patients had normal endoscopy, of these 6/10 (60%) had abnormal CT scan. Sensitivity and specificity of diagnostic nasal endoscopy against CT scan were 91% (95% CI: 81 97) and 44% (95% CI: 14-79), respectively. The likelihood ratio for positive nasal endoscopy to diagnose chronic rhino-sinusitis was 1.6 and the likelihood ratio to rule out chronic rhino-sinusitis when endoscopy was negative was 0.2. CONCLUSION: Nasal endoscopy is a valid and objective diagnostic tool in the work up of patients with symptomatic chronic rhino-sinusitis. When clinical suspicion is low (<50%) and endoscopy is negative, the probability of rhino-sinusitis is very low (<17%) and there is no need to perform a CT scan to reconfirm this finding routinely. Endoscopy alone is able to diagnose chronic rhino-sinusitis in >90% of patients when clinical suspicion is high (88%) as defined in this study by AAO-HNS Task Force criteria. Negative endoscopy, however, does not totally exclude the sinus disease in patients fulfilling task force criteria. CT scan may be needed on follow-up if there is clinical suspicion in 10% of these patients who are negative on endoscopy if symptoms persists. It is thus possible to reduce the number of CT scans if patients are carefully selected based on clinical criteria and endoscopy is done initially as part of their evaluation. PMID- 24223248 TI - Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene. AB - OBJECTIVES: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for undertaking the current study. METHODS: The prevalence and the potential prognostic impact of FLT3 mutations in 39 acute myeloid leukemia patients were analyzed by genomic polymerase chain reaction. Twelve samples with FLT3/ITDs and 27 acute myeloid leukemia samples without the mutations were compared with respect to clinical prognosis and FAB subtype. Results were correlated with cytogenetic data and the clinical response. RESULTS: FLT3/ITD mutations were found in 31% of patients. FLT3/ITD was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype (83%). Interestingly, half of the FLT3/ITD aberrations were found in patients with FAB M1 (50%), and fewer were found in patients with FAB M2 (8%), M4 (8%), and M5 (8%). Although less frequent in patients with cytogenetic aberrations, FLT3/ITDs were found in 17% of patients with t(15;17). Although the study was powered to 80%, patients with FLT3/ITD mutation did not show shorter complete remission duration or a higher relapse rate. CONCLUSION: The data confirm that FLT3/ITD mutations represent a common alteration in adult acute myeloid leukemia, mainly with normal karyotype (83%) and de novo acute myeloid leukemia (75%), as compared to secondary acute myeloid leukemia (25%) (p<0.001). It also showed that half of the M1-FAB subtype is FLT3/ITD positive. Therefore, FLT3/ITD is a therapeutic target, and thus inhibition of FLT3 tyrosine kinase activity may provide a new approach in the treatment of leukemia carrying these mutations. PMID- 24223249 TI - Solid pseudopapillary neoplasm of the pancreas: a case report with review of the diagnostic dilemmas and tumor behavior. AB - Solid pseudopapillary neoplasm of the pancreas is a rare tumor of the pancreas often detected initially on imaging. Of uncertain histogenesis, it has a low grade malignant potential with excellent post-surgical curative rates and rare metastasis. Despite advances in imaging, pseudocysts and other cystic neoplasms feature in the differential diagnosis. Pathological and/or cytological evaluation remains the gold standard in reaching a definitive diagnosis. On morphology alone, other primary pancreatic tumors and metastatic tumors pose a diagnostic challenge. Recent advances in immunohistochemical characterization have made the histopathologic diagnosis more specific and, in turn, shed light on the likely histogenesis of this rare tumor. We report a case of solid pseudopapillary neoplasm of the pancreas that was suspected on radiology and diagnosed intraoperatively on imprint cytology guiding definitive surgery. The diagnostic dilemmas are reviewed. PMID- 24223250 TI - A case of metatropic dysplasia: operative treatment of severe kyphoscoliosis and limb deformities. AB - Metatropic dysplasia is a rare but severe spondyloepimetaphyseal dysplasia characterized by long trunk and short extremities. The exact incidence is not known; however, 81 cases have been reported in the literature till now. Due to progressive kyphoscoliosis, there is a reversal of proportions in childhood (shortening of trunk with relative long extremities). The diagnostic radiographic findings include marked platyspondyly (wafer-thin vertebral bodies), widened metaphyses (dumbbell-shaped tubular bones) and small epiphysis and a specific pelvic shape. The severe kyphoscoliosis is relentless and resistant to conservative treatment with bracing. Operative treatment is controversial due to the recurrence of deformity despite aggressive correction. We, herein report a case of this rare dysplasia and its follow-up after corrective surgery for spine and limb deformity. The excellent correction and good functional pulmonary status at 6-year follow-up has never been previously reported. PMID- 24223251 TI - Patients with black hip and black knee due to ochronotic arthropathy: case report and review of literature. AB - Ochronotic arthropathy is a manifestation of longstanding alkaptonuria. With increasing age, an accumulation of pigment deposits of homogentisic acid in the joint cartilage results in ochronotic osteoarthritis. We present a case of a 62 year-old female who underwent staged left uncemented total hip and right cemented total knee arthroplasty for osteoarthritis secondary to ochronosis. PMID- 24223252 TI - Computer literacy improvement needs: physicians' self assessment in the makkah region. AB - OBJECTIVE: A confidential inquiry by the Directorate General of health affairs, Makkah region, Saudi Arabia, found physicians were resistant to enter patient related information in the electronic medical records system at different hospitals. This study aims to highlight their computer literacy needs. METHODS: This cross-sectional survey was conducted on physicians using a structured questionnaire bearing nine questions/stems with dichotomous answers, (i.e., yes/no) that was distributed among physicians at six different Ministry of Health hospitals in the Makkah Region, Saudi Arabia, between May and August 2009. The results for future needs in computer skills were categorized as "none" if the rate of answer "yes" to any stem was 0-25%, "little" if 26-50%, "some" if 51-75% and "substantial" if >75% rated "yes". RESULTS: The response rate of 82% of determined sample size (n = 451) was attained. Computer literacy improvement elements (CLIE), i.e., "word processing software skills (MS Word)", "presentation software skills (Power Point)", "internet search skills", "medical database search skills", "spreadsheet software skills (Excel)" and "advanced e-mail management skills" were in "substantial" need of improvement among the majority of settings and categories. All other computer literacy improvement elements were in "some" need of improvement. CONCLUSION: The overall outcome of this study indicates that physicians need further computer literacy improvements. PMID- 24223253 TI - Validation of the arabic version of the epworth sleepiness scale in oman. AB - OBJECTIVES: The Epworth sleepiness scale is a self-administered eight-item questionnaire that was developed as a tool to measure subjective sleepiness in adults. The validity of the Epworth sleepiness scale has been validated and tested in different populations and ethnic groups. However, it has yet to be validated or tested in an Omani or other Arabic speaking population. Thus, the aim of this study is to test the validity and reproducibility of the Epworth sleepiness scale in an Omani population. METHODS: Subjects were recruited from the general population and were asked to participate in the study. The study enrolled 97 Omani volunteers and was conducted between May and October 2008. An Arabic version of the original English questionnaire was used. The study was approved by the Research and Ethics committee of the institution. Lin's concordance correlation coefficient along with Bland-Altman plots were used to test the agreement between the Arabic and English versions of the Epworth sleepiness scale. RESULTS: The study included a total of 37 males (38%) and 60 females (62%) with age ranging between 18-75 years. Concordance correlation results revealed a substantial concordance (RhoC) of 0.914, but one that does not approach 1 (95% CI: 0.881, 0.947). This results from both lack of perfect correlation (Pearson's r=0.914) and bias (C_b = 1.000). The Bland and Altman's limits-of-agreement measured at 0.000 (95% CI: -2.684, 2.684), indicating insignificant average departure from agreement between the two versions of the Epworth sleepiness scale. CONCLUSION: The results indicate agreement between the two versions of ESS (English and the Arabic). PMID- 24223254 TI - A patient with left cardiophrenic angle mass presenting with intermittent chest symptoms. PMID- 24223255 TI - RE: Celiac Disease Prevalence in Omani Children with Type 1 Diabetes Mellitus. PMID- 24223256 TI - Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. AB - INTRODUCTION: In recent years, there has been an exponential increase in the number of studies aiming to understand the biology of exosomes, as well as other extracellular vesicles. However, classification of membrane vesicles and the appropriate protocols for their isolation are still under intense discussion and investigation. When isolating vesicles, it is crucial to use systems that are able to separate them, to avoid cross-contamination. METHOD: EVS RELEASED FROM THREE DIFFERENT KINDS OF CELL LINES: HMC-1, TF-1 and BV-2 were isolated using two centrifugation-based protocols. In protocol 1, apoptotic bodies were collected at 2,000*g, followed by filtering the supernatant through 0.8 um pores and pelleting of microvesicles at 12,200*g. In protocol 2, apoptotic bodies and microvesicles were collected together at 16,500*g, followed by filtering of the supernatant through 0.2 um pores and pelleting of exosomes at 120,000*g. Extracellular vesicles were analyzed by transmission electron microscopy, flow cytometry and the RNA profiles were investigated using a Bioanalyzer((r)). RESULTS: RNA profiles showed that ribosomal RNA was primary detectable in apoptotic bodies and smaller RNAs without prominent ribosomal RNA peaks in exosomes. In contrast, microvesicles contained little or no RNA except for microvesicles collected from TF-1 cell cultures. The different vesicle pellets showed highly different distribution of size, shape and electron density with typical apoptotic body, microvesicle and exosome characteristics when analyzed by transmission electron microscopy. Flow cytometry revealed the presence of CD63 and CD81 in all vesicles investigated, as well as CD9 except in the TF-1-derived vesicles, as these cells do not express CD9. CONCLUSIONS: Our results demonstrate that centrifugation based protocols are simple and fast systems to distinguish subpopulations of extracellular vesicles. Different vesicles show different RNA profiles and morphological characteristics, but they are indistinguishable using CD63-coated beads for flow cytometry analysis. PMID- 24223257 TI - Characterisation of tissue factor-bearing extracellular vesicles with AFM: comparison of air-tapping-mode AFM and liquid Peak Force AFM. AB - INTRODUCTION: Extracellular vesicles (EVs) are shed from cells and carry markers of the parent cells. Vesicles derived from cancer cells reach the bloodstream and locally influence important physiological processes. It has been previously shown that procoagulant vesicles are circulating in patients' fluids. These EVs are therefore considered as promising biomarkers for the thrombotic risk. Because of their small size, classical methods such as flow cytometry suffer from limitation for their characterisation. Atomic force microscopy (AFM) has been proposed as a promising complementary method for the characterisation of EVs. OBJECTIVES: THE OBJECTIVES OF THIS STUDY ARE: (a) to develop and validate AFM with specific antibodies (anti-TF) and (b) to compare air and liquid modes for EVs' size and number determination as potential biomarkers of the prothrombotic risk. METHODS: AFM multimode nanoscope III was used for air tapping mode (TM). AFM catalyst was used for liquid Peak Force Tapping (PFT) mode. Vesicles are generated according to Davila et al.'s protocol. Substrates are coated with various concentrations of antibodies, thanks to ethanolamine and glutaraldehyde. RESULTS: Vesicles were immobilised on antibody-coated surfaces to select tissue factor (TF)-positive vesicles. The size range of vesicles observed in liquid PFT mode is 6-10 times higher than in air mode. This corresponds to the data found in the literature. CONCLUSION: We recommend liquid PFT mode to analyse vesicles on 5 ug/ml antibody coated substrates. PMID- 24223258 TI - Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. AB - BACKGROUND: In 2001, it was postulated that tumour-derived exosomes could be a potent source of tumour-associated antigens (TAA). Since then, much knowledge is gained on their role in tumorigenesis but only very recently tumour-derived exosomes were used in dendritic cell (DC)-based immunotherapy. For this, DCs were cultured ex-vivo and loaded with exosomes derived from immunogenic tumours such as melanoma or glioma and re-administrated to induce anti-tumour responses in primary and metastatic tumour mouse models. In contrast, malignant mesothelioma (MM) is a non-immunogenic tumour and because only a few mesothelioma-specific TAA are known to date, we investigated whether mesothelioma-derived exosomes could be used as antigen source in DC-based immunotherapy. METHODS: Mouse MM AB1 cells were used to generate tumour lysate and tumour-derived exosomes. Tumour lysate was generated by 5 cycles of freeze-thawing followed by sonication of AB1 cells. Tumour exosomes were collected from the AB1 cell culture supernatant and followed a stepwise ultracentrifugation. Protein quantification and electron microscopy were performed to determine the protein amount and to characterise their morphology. To test whether MM derived exosomes are immunogenic and able to stimulate an anti-tumoral response, BALB/c mice were injected with a lethal dose of AB1 tumour cells at day 0, followed by intraperitoneal injection of a single dose of DCs loaded with tumour exosomes, DCs loaded with tumour lysate, or phosphate buffered saline (PBS), at day 7. RESULTS: Mice which received tumour exosome-loaded DC immunotherapy had an increased median and overall survival compared to mice which received tumour lysate-loaded DC or PBS. CONCLUSION: In this study, we showed that DC immunotherapy loaded with tumour exosomes derived from non-immunogenic tumours improved survival of tumour bearing mice. PMID- 24223259 TI - Cancer becomes wasteful: emerging roles of exosomes(?) in cell-fate determination. AB - Extracellular vesicles (EVs), including exosomes, have been widely recognized for their role in intercellular communication of the immune response system. In the past few years, significance has been given to exosomes in the induction and modulation of cell-fate-inducing signalling pathways, such as the Hedgehog (Hh), Wnts, Notch, transforming growth factor (TGF-beta), epidermal growth factor (EGF) and fibroblast growth factor (FGF) pathways, placing them in the wider context of development and also of cancer. These protein families induce signalling cascades responsible for tissue specification, homeostasis and maintenance. Exosomes contribute to cell-fate signal secretion, and vice versa exosome secretion can be induced by these proteins. Interestingly, exosomes can also transfer their mRNA to host cells or modulate the signalling pathways directly by the removal of downstream effector molecules from the cell. Surprisingly, much of what we know about the function of exosomes in cell determination is gathered from pathological transformed cancer cells and wound healing while data about their biogenesis and biology in normal developing and adult tissue lag behind. In this report, we will summarize some of the published literature and point to current advances and questions in this fast-developing topic. In a brief foray, we will also update and shortly discuss their potential in diagnosis and targeted cancer treatment. PMID- 24223260 TI - Understanding the Consequences of Bilingualism for Language Processing and Cognition. AB - Contemporary research on bilingualism has been framed by two major discoveries. In the realm of language processing, studies of comprehension and production show that bilinguals activate information about both languages when using one language alone. Parallel activation of the two languages has been demonstrated for highly proficient bilinguals as well as second language learners and appears to be present even when distinct properties of the languages themselves might be sufficient to bias attention towards the language in use. In the realm of cognitive processing, studies of executive function have demonstrated a bilingual advantage, with bilinguals outperforming their monolingual counterparts on tasks that require ignoring irrelevant information, task switching, and resolving conflict. Our claim is that these outcomes are related and have the overall effect of changing the way that both cognitive and linguistic processing are carried out for bilinguals. In this article we consider each of these domains of bilingual performance and consider the kinds of evidence needed to support this view. We argue that the tendency to consider bilingualism as a unitary phenomenon explained in terms of simple component processes has created a set of apparent controversies that masks the richness of the central finding in this work: the adult mind and brain are open to experience in ways that create profound consequences for both language and cognition. PMID- 24223261 TI - Evolutionary history of rat-borne Bartonella: the importance of commensal rats in the dissemination of bacterial infections globally. AB - Emerging pathogens that originate from invasive species have caused numerous significant epidemics. Some bacteria of genus Bartonella are rodent-borne pathogens that can cause disease in humans and animals alike. We analyzed gltA sequences of 191 strains of rat-associated bartonellae from 29 rodent species from 17 countries to test the hypotheses that this bacterial complex evolved and diversified in Southeast Asia before being disseminated by commensal rats Rattus rattus (black rat) and Rattus norvegicus (Norway rat) to other parts of the globe. The analysis suggests that there have been numerous dispersal events within Asia and introductions from Asia to other regions, with six major clades containing Southeast Asian isolates that appear to have been dispersed globally. Phylogeographic analyses support the hypotheses that these bacteria originated in Southeast Asia and commensal rodents (R. rattus and R. norvegicus) play key roles in the evolution and dissemination of this Bartonella complex throughout the world. PMID- 24223262 TI - Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa. AB - Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted "mountain refugia hypothesis" states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity. PMID- 24223263 TI - Spatial phenotypic and genetic structure of threespine stickleback (Gasterosteus aculeatus) in a heterogeneous natural system, Lake Myvatn, Iceland. AB - Eco-evolutionary responses of natural populations to spatial environmental variation strongly depend on the relative strength of environmental differences/natural selection and dispersal/gene flow. In absence of geographic barriers, as often is the case in lake ecosystems, gene flow is expected to constrain adaptive divergence between environments - favoring phenotypic plasticity or high trait variability. However, if divergent natural selection is sufficiently strong, adaptive divergence can occur in face of gene flow. The extent of divergence is most often studied between two contrasting environments, whereas potential for multimodal divergence is little explored. We investigated phenotypic (body size, defensive structures, and feeding morphology) and genetic (microsatellites) structure in threespine stickleback (Gasterosteus aculeatus) across five habitat types and two basins (North and South) within the geologically young and highly heterogeneous Lake Myvatn, North East Iceland. We found that (1) North basin stickleback were, on average, larger and had relatively longer spines than South basin stickleback, whereas (2) feeding morphology (gill raker number and gill raker gap width) differed among three of five habitat types, and (3) there was only subtle genetic differentiation across the lake. Overall, our results indicate predator and prey mediated phenotypic divergence across multiple habitats in the lake, in face of gene flow. PMID- 24223265 TI - Spatial and temporal changes in bird assemblages in forest fragments in an eastern Amazonian savannah. AB - We investigated the effects of forest fragmentation on bird assemblages in an Amazonian savannah landscape with forest fragments that have been isolated for more than 100 years. The study was conducted in areas surrounding the village of Alter do Chao (2 degrees 31'S, 55 degrees 00'W), Santarem, Brazil. Bird surveys and measurements of tree density were undertaken in 25 areas, with 19 plots in forest fragments of different sizes and six in an area of continuous forest. Data on forest-fragment size, perimeter, and isolation were obtained from a georeferenced satellite image. Variation in number of bird species recorded per plot was not related to vegetation structure (tree density). The number of bird species recorded per plot increased significantly only with fragment area, but was not influenced by fragment shape or degree of isolation, even when considering species from the savannah matrix in the analysis. Fragments had fewer rare species. Multivariate ordination analyses (multiple dimensional scaling, [MDS]) indicated that bird species composition changed along a gradient from small to large forest fragments and continuous-forest areas. In the Amazonian savannah landscapes of Alter do Chao, the organization and composition of bird assemblages in forest fragments are affected by local long-term forest fragmentation processes. Differences in the number of bird species recorded per plot and assemblage composition between forest fragments and continuous forest were not influenced by forest structure, suggesting that the observed patterns in species composition result from the effects of fragmentation per se rather than from preexisting differences in vegetation structure between sites. Nevertheless, despite their long history of isolation, the forest fragments still preserve a large proportion (on average 80%) of the avifauna found in continuous-forest areas. The fragments at Alter do Chao are surrounded by natural (rather than planted) grassland, with many trees in the savannah matrix and the landscape has vast areas covered by forest, which may have helped to ameliorate the influences of forest fragmentation. PMID- 24223264 TI - Genetic structure and demographic history of the endangered tree species Dysoxylum malabaricum (Meliaceae) in Western Ghats, India: implications for conservation in a biodiversity hotspot. AB - The impact of fragmentation by human activities on genetic diversity of forest trees is an important concern in forest conservation, especially in tropical forests. Dysoxylum malabaricum (white cedar) is an economically important tree species, endemic to the Western Ghats, India, one of the world's eight most important biodiversity hotspots. As D. malabaricum is under pressure of disturbance and fragmentation together with overharvesting, conservation efforts are required in this species. In this study, range-wide genetic structure of twelve D. malabaricum populations was evaluated to assess the impact of human activities on genetic diversity and infer the species' evolutionary history, using both nuclear and chloroplast (cp) DNA simple sequence repeats (SSR). As genetic diversity and population structure did not differ among seedling, juvenile and adult age classes, reproductive success among the old-growth trees and long distance seed dispersal by hornbills were suggested to contribute to maintain genetic diversity. The fixation index (F IS) was significantly correlated with latitude, with a higher level of inbreeding in the northern populations, possibly reflecting a more severe ecosystem disturbance in those populations. Both nuclear and cpSSRs revealed northern and southern genetic groups with some discordance of their distributions; however, they did not correlate with any of the two geographic gaps known as genetic barriers to animals. Approximate Bayesian computation-based inference from nuclear SSRs suggested that population divergence occurred before the last glacial maximum. Finally we discussed the implications of these results, in particular the presence of a clear pattern of historical genetic subdivision, on conservation policies. PMID- 24223266 TI - Tropical rain forest conservation and the twin challenges of diversity and rarity. AB - Data from a global network of large, permanent plots in lowland tropical forests demonstrate (1) that the phenomenon of tropical tree rarity is real and (2) that almost all the species diversity in such forests is due to rare species. Theoretical and empirically based reasoning suggests that many of these rare species are not as geographically widespread as previously thought. These findings suggest that successful strategies for conserving global tree diversity in lowland tropical forests must pay much more attention to the biogeography of rarity, as well as to the impact of climate change on the distribution and abundance of rare species. Because the biogeography of many tropical tree species is poorly known, a high priority should be given to documenting the distribution and abundance of rare tropical tree species, particularly in Amazonia, the largest remaining tropical forested region in the world. PMID- 24223267 TI - Did southern Western Ghats of peninsular India serve as refugia for its endemic biota during the Cretaceous volcanism? AB - The Western Ghats (WG) of south India, a global biodiversity hotspot, has experienced complex geological history being part of Gondwana landmass and encountered extensive volcanic activity at the end of Cretaceous epoch. It also has a climatically and topographically heterogeneous landscape. Thus, the WG offer a unique setting to explore the influence of ecological and geological processes on the current diversity and distribution of its biota. To this end, three explicit biogeographical scenarios were hypothesized to evaluate the distribution and diversification of wet evergreen species of the WG - (1) southern WG was a refuge for the wet evergreen species during the Cretaceous volcanism, (2) phylogenetic breaks in the species phylogeny would correspond to geographic breaks (i.e., the Palghat gap) in the WG, and (3) species from each of the biogeographic subdivisions within the WG would form distinct clades. These hypotheses were tested on the centipede genus Digitipes from the WG which is known to be an ancient, endemic, and monophyletic group. The Digitipes molecular phylogeny was subjected to divergence date estimation using Bayesian approach, and ancestral areas were reconstructed using parsimony approach for each node in the phylogeny. Ancestral-area reconstruction suggested 13 independent dispersal events to explain the current distribution of the Digitipes species in the WG. Among these 13 dispersals, two dispersal events were at higher level in the Digitipes phylogeny and were from the southern WG to the central and northern WG independently in the Early Paleocene, after the Cretaceous Volcanism. The remaining 11 dispersal events explained the species' range expansions of which nine dispersals were from the southern WG to other biogeographic subdivisions in the Eocene-Miocene in the post-volcanic periods where species-level diversifications occurred. Taken together, these results suggest that southern WG might have served as a refuge for Digitipes species during Cretaceous volcanism. PMID- 24223268 TI - Identification of molecular and physiological responses to chronic environmental challenge in an invasive species: the Pacific oyster, Crassostrea gigas. AB - Understanding the environmental responses of an invasive species is critical in predicting how ecosystem composition may be transformed in the future, especially under climate change. In this study, Crassostrea gigas, a species well adapted to the highly variable intertidal environment, was exposed to the chronic environmental challenges of temperature (19 and 24 degrees C) and pH (ambient seawater and a reduction of 0.4 pH units) in an extended 3-month laboratory-based study. Physiological parameters were measured (condition index, shell growth, respiration, excretion rates, O:N ratios, and ability to repair shell damage) alongside molecular analyses. Temperature was by far the most important stressor, as demonstrated by reduced condition indexes and shell growth at 24 degrees C, with relatively little effect detected for pH. Transcriptional profiling using candidate genes and SOLiD sequencing of mantle tissue revealed that classical "stress" genes, previously reported to be upregulated under acute temperature challenges, were not significantly expressed in any of the treatments, emphasizing the different response between acute and longer term chronic stress. The transcriptional profiling also elaborated on the cellular responses underpinning the physiological results, including the identification of the PI3K/AKT/mTOR pathway as a potentially novel marker for chronic environmental challenge. This study represents a first attempt to understand the energetic consequences of cumulative thermal stress on the intertidal C. gigas which could significantly impact on coastal ecosystem biodiversity and function in the future. PMID- 24223269 TI - Age-specific responses to spring temperature in a migratory songbird: older females attempt more broods in warmer springs. AB - Increasing global temperature has led to an interest in plasticity in the timing of annual events; however, little is known about the demographic consequences of changing phenology. Annual reproductive success varies significantly among individuals within a population, and some of that variation has to do with the number of broods attempted by reproducing adults. In birds, female age and the timing of reproduction are often predictors of multiple breeding. We hypothesize that double brooding rates may be affected by spring temperature and that the response may vary with female age. We used a long-term reproductive data set for a migratory songbird, the prothonotary warbler (Protonotaria citrea) to assess which factors influence (a) an individual female's probability of double brooding and (b) the annual variation in population-level double brooding rates. We found that older and earlier nesting birds are more likely to double brood, and that there is no evidence for senescence with regard to this trait such that the oldest females were most likely to double brood. Previous experience with double brooding (i.e., whether the female double brooded in the previous year) significantly increased the probability of doing so again. When assessing annual variation in the double brooding rate, we found an interaction between spring temperature and the proportion of older females in the population. Specifically, older females are more likely to double brood in years with warmer springs, but this relationship was not seen for younger females. Previous studies have shown that warmer temperatures lead to earlier and narrower peaks in resources and we hypothesize that these peaks are more available to older and earlier arriving females, enabling them to successfully raise more than one brood in a season. Understanding how different age classes respond to changing environmental conditions will be imperative to managing declining species. PMID- 24223270 TI - Dramatic response to climate change in the Southwest: Robert Whittaker's 1963 Arizona Mountain plant transect revisited. AB - Models analyzing how Southwestern plant communities will respond to climate change predict that increases in temperature will lead to upward elevational shifts of montane species. We tested this hypothesis by reexamining Robert Whittaker's 1963 plant transect in the Santa Catalina Mountains of southern Arizona, finding that this process is already well underway. Our survey, five decades after Whittaker's, reveals large changes in the elevational ranges of common montane plants, while mean annual rainfall has decreased over the past 20 years, and mean annual temperatures increased 0.25 degrees C/decade from 1949 to 2011 in the Tucson Basin. Although elevational changes in species are individualistic, significant overall upward movement of the lower elevation boundaries, and elevational range contractions, have occurred. This is the first documentation of significant upward shifts of lower elevation range boundaries in Southwestern montane plant species over decadal time, confirming that previous hypotheses are correct in their prediction that mountain communities in the Southwest will be strongly impacted by warming, and that the Southwest is already experiencing a rapid vegetation change. PMID- 24223271 TI - Origin and demographic history of the endemic Taiwan spruce (Picea morrisonicola). AB - Taiwan spruce (Picea morrisonicola) is a vulnerable conifer species endemic to the island of Taiwan. A warming climate and competition from subtropical tree species has limited the range of Taiwan spruce to the higher altitudes of the island. Using seeds sampled from an area in the central mountain range of Taiwan, 15 nuclear loci were sequenced in order to measure genetic variation and to assess the long-term genetic stability of the species. Genetic diversity is low and comparable to other spruce species with limited ranges such as Picea breweriana, Picea chihuahuana, and Picea schrenkiana. Importantly, analysis using approximate Bayesian computation (ABC) provides evidence for a drastic decline in the effective population size approximately 0.3-0.5 million years ago (mya). We used simulations to show that this is unlikely to be a false-positive result due to the limited sample used here. To investigate the phylogenetic origin of Taiwan spruce, additional sequencing was performed in the Chinese spruce Picea wilsonii and combined with previously published data for three other mainland China species, Picea purpurea, Picea likiangensis, and P. schrenkiana. Analysis of population structure revealed that P. morrisonicola clusters most closely with P. wilsonii, and coalescent analyses using the program MIMAR dated the split to 4-8 mya, coincidental to the formation of Taiwan. Considering the population decrease that occurred after the split, however, led to a much more recent origin. PMID- 24223272 TI - Climate change, species distribution models, and physiological performance metrics: predicting when biogeographic models are likely to fail. AB - Modeling the biogeographic consequences of climate change requires confidence in model predictions under novel conditions. However, models often fail when extended to new locales, and such instances have been used as evidence of a change in physiological tolerance, that is, a fundamental niche shift. We explore an alternative explanation and propose a method for predicting the likelihood of failure based on physiological performance curves and environmental variance in the original and new environments. We define the transient event margin (TEM) as the gap between energetic performance failure, defined as CTmax, and the upper lethal limit, defined as LTmax. If TEM is large relative to environmental fluctuations, models will likely fail in new locales. If TEM is small relative to environmental fluctuations, models are likely to be robust for new locales, even when mechanism is unknown. Using temperature, we predict when biogeographic models are likely to fail and illustrate this with a case study. We suggest that failure is predictable from an understanding of how climate drives nonlethal physiological responses, but for many species such data have not been collected. Successful biogeographic forecasting thus depends on understanding when the mechanisms limiting distribution of a species will differ among geographic regions, or at different times, resulting in realized niche shifts. TEM allows prediction of the likelihood of such model failure. PMID- 24223273 TI - Sweeping beauty: is grassland arthropod community composition effectively estimated by sweep netting? AB - Arthropods are critical ecosystem components due to their high diversity and sensitivity to perturbation. Furthermore, due to their ease of capture they are often the focus of environmental health surveys. There is much debate regarding the best sampling method to use in these surveys. Sweep netting and pan trapping are two sampling methods commonly used in agricultural arthropod surveys, but have not been contrasted in natural grassland systems at the community level. The purpose of this study was to determine whether sweep netting was effective at estimating arthropod diversity at the community level in grasslands or if supplemental pan trapping was needed. Arthropods were collected from grassland sites in Montana, USA, in the summer of 2011. The following three standardized evaluation criteria (consistency, reliability, and precision) were developed to assess the efficacy of sweep netting and pan trapping, based on analyses of variations in arthropod abundances, species richness, evenness, capture frequency, and community composition. Neither sampling method was sufficient in any criteria to be used alone for community-level arthropod surveys. On a taxa specific basis, however, sweep netting was consistent, reliable, and precise for Thysanoptera, infrequently collected (i.e., rare) insects, and Arachnida, whereas pan trapping was consistent, reliable, and precise for Collembola and bees, which is especially significant given current threats to the latter's populations worldwide. Species-level identifications increase the detected dissimilarity between sweep netting and pan trapping. We recommend that community-level arthropod surveys use both sampling methods concurrently, at least in grasslands, but likely in most nonagricultural systems. Target surveys, such as monitoring bee communities in fragmented grassland habitat or where detailed information on behavior of the target arthropod groups is available can in some instances employ singular methods. As a general ecological principle, consistency, reliability, and precision are appropriate criteria to evaluate the applicability of a given sampling method for both community-level and taxa-specific arthropod surveys in any ecosystem. PMID- 24223274 TI - Less can be more: loss of MHC functional diversity can reflect adaptation to novel conditions during fish invasions. AB - The ability of invasive species to adapt to novel conditions depends on population size and environmental mismatch, but also on genetic variation. Away from their native range, invasive species confronted with novel selective pressures may display different levels of neutral versus functional genetic variation. However, the majority of invasion studies have only examined genetic variation at neutral markers, which may reveal little about how invaders adapt to novel environments. Salmonids are good model systems to examine adaptation to novel pressures because they have been translocated all over the world and represent major threats to freshwater biodiversity in the Southern Hemisphere, where they have become invasive. We examined patterns of genetic differentiation at seven putatively neutral (microsatellites) loci and one immune-related major histocompatibility complex (MHC class II-beta) locus among introduced rainbow trout living in captivity (farmed) or under natural conditions (naturalized) in Chilean Patagonia. A significant positive association was found between differentiation at neutral and functional markers, highlighting the role of neutral evolutionary forces in shaping genetic variation at immune-related genes in salmonids. However, functional (MHC) genetic diversity (but not microsatellite diversity) decreased with time spent in the wild since introduction, suggesting that there was selection against alleles associated with captive rearing of donor populations that do not provide an advantage in the wild. Thus, although high genetic diversity may initially enhance fitness in translocated populations, it does not necessarily reflect invasion success, as adaptation to novel conditions may result in rapid loss of functional MHC diversity. PMID- 24223275 TI - Experimental demonstration of accelerated extinction in source-sink metapopulations. AB - Population extinction is a fundamental ecological process which may be aggravated by the exchange of organisms between productive (source) and unproductive (sink) habitat patches. The extent to which such source-sink exchange affects extinction rates is unknown. We conducted an experiment in which metapopulation effects could be distinguished from source-sink effects in laboratory populations of Daphnia magna. Time-to-extinction in this experiment was maximized at intermediate levels of habitat fragmentation, which is consistent with a minority of theoretical models. These results provided a baseline for comparison with experimental treatments designed to detect effects of concentrating resources in source patches. These treatments showed that source-sink configurations increased population variability (the coefficient of variation in abundance) and extinction hazard compared with homogeneous environments. These results suggest that where environments are spatially heterogeneous, accurate assessments of extinction risk will require understanding the exchange of organisms among population sources and sinks. Such heterogeneity may be the norm rather than the exception because of both the intrinsic heterogeneity naturally exhibited by ecosystems and increasing habitat fragmentation by human activity. PMID- 24223276 TI - Mixed asexual and sexual reproduction in the Indo-Pacific reef coral Pocillopora damicornis. AB - Pocillopora damicornis is one of the best studied reef-building corals, yet it's somewhat unique reproductive strategy remains poorly understood. Genetic studies indicate that P. damicornis larvae are produced almost exclusively parthenogenetically, and yet population genetic surveys suggest frequent sexual reproduction. Using microsatellite data from over 580 larvae from 13 colonies, we demonstrate that P. damicornis displays a mixed reproductive strategy where sexual and asexual larvae are produced simultaneously within the same colony. The majority of larvae were parthenogenetic (94%), but most colonies (10 of the 13) produced a subset of their larvae sexually. Logistic regression indicates that the proportion of sexual larvae varied significantly with colony size, cycle day, and calendar day. In particular, the decrease in sexual larvae with colony size suggests that the mixed reproductive strategy changes across the life of the coral. This unique shift in reproductive strategy leads to increasingly asexual replications of successful genotypes, which (in contrast to exclusive parthenogens) have already contributed to the recombinant gene pool. PMID- 24223277 TI - Population genetics structure of glyphosate-resistant Johnsongrass (Sorghum halepense L. Pers) does not support a single origin of the resistance. AB - Single sequence repeats (SSR) developed for Sorghum bicolor were used to characterize the genetic distance of 46 different Sorghum halepense (Johnsongrass) accessions from Argentina some of which have evolved toward glyphosate resistance. Since Johnsongrass is an allotetraploid and only one subgenome is homologous to cultivated sorghum, some SSR loci amplified up to two alleles while others (presumably more conserved loci) amplified up to four alleles. Twelve SSR providing information of 24 loci representative of Johnsongrass genome were selected for genetic distance characterization. All of them were highly polymorphic, which was evidenced by the number of different alleles found in the samples studied, in some of them up to 20. UPGMA and Mantel analysis showed that Johnsongrass glyphosate-resistant accessions that belong to different geographic regions do not share similar genetic backgrounds. In contrast, they show closer similarity to their neighboring susceptible counterparts. Discriminant Analysis of Principal Components using the clusters identified by K-means support the lack of a clear pattern of association among samples and resistance status or province of origin. Consequently, these results do not support a single genetic origin of glyphosate resistance. Nucleotide sequencing of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) encoding gene from glyphosate-resistant and susceptible accessions collected from different geographic origins showed that none presented expected mutations in aminoacid positions 101 and 106 which are diagnostic of target-site resistance mechanism. PMID- 24223278 TI - Predicting rarity and decline in animals, plants, and mushrooms based on species attributes and indicator groups. AB - In decisions on nature conservation measures, we depend largely on knowledge of the relationship between threats and environmental factors for a very limited number of species groups, with relevant environmental factors often being deduced from the relationship between threat and species traits. But can relationships between traits and levels of threats be identified across species from completely different taxonomic groups; and how accurately do well-known taxonomic groups indicate levels of threat in other species groups? To answer these questions, we first made a list of 152 species attributes of morphological and demographic traits and habitat requirements. Based on these attributes we then grew random forests of decision trees for 1183 species in the 18 different taxonomic groups for which we had Red Lists available in the Netherlands, using these to classify animals, plants, and mushrooms according to their rarity and decline. Finally, we grew random forests for four species groups often used as indicator groups to study how well the relationship between attribute and decline within these groups reflected that relationship within the larger taxonomic group to which these groups belong. Correct classification of rarity based on all attributes was as high as 88% in animals, 85% in plants, and 94% in mushrooms and correct classification of decline was 78% in animals, 69% in plants, and 70% in mushrooms. Vertebrates indicated decline in all animals well, as did birds for all vertebrates and vascular plants for all plants. However, butterflies poorly indicated decline in all insects. Random forests are a useful tool to relate rarity and decline to species attributes thereby making it possible to generalize rarity and decline to a wider set of species groups. Random forests can be used to estimate the level of threat to complete faunas and floras of countries or regions. In regions like the Netherlands, conservation policy based on attributes known to be relevant for the decline to birds, vertebrates or plants will probably also impact all aboveground terrestrial and freshwater macrofauna or macrophytes. PMID- 24223279 TI - "Forms" of water mites (Acari: Hydrachnidia): intraspecific variation or valid species? AB - In many groups of organisms, especially in the older literature, it has been common practice to recognize sympatrically occurring phenotypic variants of a species as "forms". However, what these forms really represent often remains unclear, especially in poorly studied groups. With new algorithms for DNA-based species delimitation, the status of forms can be explicitly tested with molecular data. In this study, we test a number of what is now recognized as valid species of water mites (Hydrachnidia), but have in the past been treated as forms sympatrically occurring with their nominate species. We also test a form without prior taxonomical status, using DNA and morphometrics. The barcoding fragment of COI, nuclear 28S and quantitative analyses of morphological data were used to test whether these taxa merit species status, as suggested by several taxonomists. Our results confirm valid species. Genetic distances between the form and nominate species (Piona dispersa and Piona variabilis, COI 11%), as well as likelihood ratio tests under the general mixed-Yule coalescent model, supported that these are separately evolving lineages as defined by the unified species concept. In addition, they can be diagnosed with morphological characters. The study also reveals that some taxa genetically represent more than one species. We propose that P. dispersa are recognized as valid taxa at the species level. Unionicola minor (which may consist of several species), Piona stjordalensis, P. imminuta s. lat., and P. rotundoides are confirmed as species using this model. The results also imply that future studies of other water mite species complexes are likely to reveal many more genetically and morphologically distinct species. PMID- 24223280 TI - Phenotypic plasticity of coralline algae in a High CO2 world. AB - It is important to understand how marine calcifying organisms may acclimatize to ocean acidification to assess their survival over the coming century. We cultured the cold water coralline algae, Lithothamnion glaciale, under elevated pCO2 (408, 566, 770, and 1024 MUatm) for 10 months. The results show that the cell (inter and intra) wall thickness is maintained, but there is a reduction in growth rate (linear extension) at all elevated pCO2. Furthermore a decrease in Mg content at the two highest CO2 treatments was observed. Comparison between our data and that at 3 months from the same long-term experiment shows that the acclimation differs over time since at 3 months, the samples cultured under high pCO2 showed a reduction in the cell (inter and intra) wall thickness but a maintained growth rate. This suggests a reallocation of the energy budget between 3 and 10 months and highlights the high degree plasticity that is present. This might provide a selective advantage in future high CO2 world. PMID- 24223281 TI - Did the house mouse (Mus musculus L.) shape the evolutionary trajectory of wheat (Triticum aestivum L.)? AB - Wheat (Triticum aestivum L.) is one of the most successful domesticated plant species in the world. The majority of wheat carries mutations in the Puroindoline genes that result in a hard kernel phenotype. An evolutionary explanation, or selective advantage, for the spread and persistence of these hard kernel mutations has yet to be established. Here, we demonstrate that the house mouse (Mus musculus L.) exerts a pronounced feeding preference for soft over hard kernels. When allele frequencies ranged from 0.5 to 0.009, mouse predation increased the hard allele frequency as much as 10-fold. Studies involving a single hard kernel mixed with ~1000 soft kernels failed to recover the mutant kernel. Nevertheless, the study clearly demonstrates that the house mouse could have played a role in the evolution of wheat, and therefore the cultural trajectory of humankind. PMID- 24223282 TI - How many marker loci are necessary? Analysis of dominant marker data sets using two popular population genetic algorithms. AB - The number of marker loci required to answer a given research question satisfactorily is especially important for dominant markers since they have a lower information content than co-dominant marker systems. In this study, we used simulated dominant marker data sets to determine the number of dominant marker loci needed to obtain satisfactory results from two popular population genetic analyses: STRUCTURE and AMOVA (analysis of molecular variance). Factors such as migration, level of population differentiation, and unequal sampling were varied in the data sets to mirror a range of realistic research scenarios. AMOVA performed well under all scenarios with a modest quantity of markers while STRUCTURE required a greater number, especially when populations were closely related. The popular DeltaK method of determining the number of genetically distinct groups worked well when sampling was balanced, but underestimated the true number of groups with unbalanced sampling. These results provide a window through which to interpret previous work with dominant markers and we provide a protocol for determining the number of markers needed for future dominant marker studies. PMID- 24223283 TI - Evidence for 20th century climate warming and wetland drying in the North American Prairie Pothole Region. AB - The Prairie Pothole Region (PPR) of North America is a globally important resource that provides abundant and valuable ecosystem goods and services in the form of biodiversity, groundwater recharge, water purification, flood attenuation, and water and forage for agriculture. Numerous studies have found these wetlands, which number in the millions, to be highly sensitive to climate variability. Here, we compare wetland conditions between two 30-year periods (1946-1975; 1976-2005) using a hindcast simulation approach to determine if recent climate warming in the region has already resulted in changes in wetland condition. Simulations using the WETLANDSCAPE model show that 20th century climate change may have been sufficient to have a significant impact on wetland cover cycling. Modeled wetlands in the PPR's western Canadian prairies show the most dramatic effects: a recent trend toward shorter hydroperiods and less dynamic vegetation cycles, which already may have reduced the productivity of hundreds of wetland-dependent species. PMID- 24223284 TI - Postcopulatory selection for dissimilar gametes maintains heterozygosity in the endangered North Atlantic right whale. AB - Although small populations are expected to lose genetic diversity through genetic drift and inbreeding, a number of mechanisms exist that could minimize this genetic decline. Examples include mate choice for unrelated mates and fertilization patterns biased toward genetically dissimilar gametes. Both processes have been widely documented, but the long-term implications have received little attention. Here, we combined over 25 years of field data with high-resolution genetic data to assess the long-term impacts of biased fertilization patterns in the endangered North Atlantic right whale. Offspring have higher levels of microsatellite heterozygosity than expected from this gene pool (effect size = 0.326, P < 0.011). This pattern is not due to precopulatory mate choice for genetically dissimilar mates (P < 0.600), but instead results from postcopulatory selection for gametes that are genetically dissimilar (effect size = 0.37, P < 0.003). The long-term implication is that heterozygosity has slowly increased in calves born throughout the study period, as opposed to the slight decline that was expected. Therefore, this mechanism represents a natural means through which small populations can mitigate the loss of genetic diversity over time. PMID- 24223285 TI - Dioecy, more than monoecy, affects plant spatial genetic structure: the case study of Ficus. AB - In this analysis, we attempt to understand how monoecy and dioecy drive spatial genetic structure (SGS) in plant populations. For this purpose, plants of the genus Ficus were used as a comparative model due to their particular characteristics, including high species diversity, variation in life histories, and sexual systems. One of the main issues we assessed is whether dioecious fig tree populations are more spatially genetically structured than monoecious populations. Using the Sp statistic, which allows for quantitative comparisons among different studies, we compared the extent of SGS between monoecious and dioecious Ficus species. To broaden our conclusions we used published data on an additional 27 monoecious and dioecious plant species. Furthermore, genetic diversity analyses were performed for two monoecious Ficus species using 12 microsatellite markers in order to strengthen our conclusions about SGS. Our results show that dioecy, more than monoecy, significantly contributes to SGS in plant populations. On average, the estimate of Sp was six times higher for dioecious Ficus species than monoecious Ficus species and it was two times higher in dioecious than monoecious plant species. Considering these results, we emphasize that the long-distance pollen dispersal mechanism in monoecious Ficus species seems to be the dominant factor in determining weak spatial genetic structure, high levels of genetic diversity, and lack of inbreeding. Although Ficus constitute a model species to study SGS, a more general comparison encompassing a wider range of plants is required in order to better understand how sexual systems affect genetic structure. PMID- 24223286 TI - What to eat now? Shifts in polar bear diet during the ice-free season in western Hudson Bay. AB - Under current climate trends, spring ice breakup in Hudson Bay is advancing rapidly, leaving polar bears (Ursus maritimus) less time to hunt seals during the spring when they accumulate the majority of their annual fat reserves. For this reason, foods that polar bears consume during the ice-free season may become increasingly important in alleviating nutritional stress from lost seal hunting opportunities. Defining how the terrestrial diet might have changed since the onset of rapid climate change is an important step in understanding how polar bears may be reacting to climate change. We characterized the current terrestrial diet of polar bears in western Hudson Bay by evaluating the contents of passively sampled scat and comparing it to a similar study conducted 40 years ago. While the two terrestrial diets broadly overlap, polar bears currently appear to be exploiting increasingly abundant resources such as caribou (Rangifer tarandus) and snow geese (Chen caerulescens caerulescens) and newly available resources such as eggs. This opportunistic shift is similar to the diet mixing strategy common among other Arctic predators and bear species. We discuss whether the observed diet shift is solely a response to a nutritional stress or is an expression of plastic foraging behavior. PMID- 24223287 TI - Effects of structural connectivity on fine scale population genetic structure of muskrat, Ondatra zibethicus. AB - In heterogeneous landscapes, physical barriers and loss of structural connectivity have been shown to reduce gene flow and therefore lead to population structuring. In this study, we assessed the influence of landscape features on population genetic structure and gene flow of a semiaquatic species, the muskrat. A total of 97 muskrats were sampled from three watersheds near Sudbury, Ontario, Canada. We estimated population genetic structure using 11 microsatellite loci and identified a single genetic cluster and no genetic differences were found among the watersheds as a result of high levels of gene flow. At finer scales, we assessed the correlation between individual pairwise genetic distances and Euclidean distance as well as different models of least cost path (LCP). We used a range of cost values for the landscape types in order to build our LCP models. We found a positive relationship between genetic distance and least cost distance when we considered roads as corridors for movements. Open landscapes and urban areas seemed to restrict but not prevent gene flow within the study area. Our study underlines the high-dispersal ability of generalist species in their use of landscape and highlights how landscape features often considered barriers to animal movements are corridors for other species. PMID- 24223288 TI - Tree size and its relationship with flowering phenology and reproductive output in Wild Nutmeg trees. AB - Reproductive strategies, sexual selection, and their relationship with the phenotype of individuals are topics widely studied in animals, but this information is less abundant for plants. Variability in flowering phenology among individuals has direct impact on their fitness, but how reproductive phenology is affected by the size of the individuals needs further study. We quantified the flowering intensity, length, and reproductive synchronization of two sympatric dioecious Wild Nutmeg tree species (Virola, Myristicaceae) in the Brazilian Atlantic forest, and analyzed its relationships with tree size. Two distinct strategies in flowering timing and intensity were found between species (annual versus biennial flowering), and among individuals in the annual flowering species (extended versus peak flowering). Only for the annual flowering species the reproductive output is related to tree size and large trees present proportionally higher flower coverage, and lower synchronization than smaller ones. Flowering is massive and highly synchronized in the biennial species. Sex ratios are not different from 1:1 in the two species, and in the two segregated reproductive subgroups in the biennial flowering species. The biennial flowering at individual level is a novelty among reproductive patterns in plants, separating the population in two reproductive subgroups. A proportional increase in the reproductive output with size exists only for the annual flowering species. A biennial flowering can allow resource storage favouring massive flowering for all the individuals diluting their relationship with size. PMID- 24223289 TI - Distinguishing the importance between habitat specialization and dispersal limitation on species turnover. AB - Understanding what governs community assembly and the maintenance of biodiversity is a central issue in ecology, but has been a continuing debate. A key question is the relative importance of habitat specialization (niche assembly) and dispersal limitation (dispersal assembly). In the middle of the Loess Plateau, northwestern China, we examined how species turnover in Liaodong oak (Quercus wutaishanica) forests differed between observed and randomized assemblies, and how this difference was affected by habitat specialization and dispersal limitation using variation partitioning. Results showed that expected species turnover based on individual randomization was significantly lower than the observed value (P < 0.01). The turnover deviation significantly depended on the environmental and geographical distances (P < 0.05). Environmental and spatial variables significantly explained approximately 40% of the species composition variation at all the three layers (P < 0.05). However, their contributions varied among forest layers; the herb and shrub layers were dominated by environmental factors, whereas the canopy layer was dominated by spatial factors. Our results underscore the importance of synthetic models that integrate effects of both dispersal and niche assembly for understanding the community assembly. However, habitat specialization (niche assembly) may not always be the dominant process in community assembly, even under harsh environments. Community assembly may be in a trait-dependent manner (e.g., forest layers in this study). Thus, taking more species traits into account would strengthen our confidence in the inferred assembly mechanisms. PMID- 24223290 TI - A natural antipredation experiment: predator control and reduced sea ice increases colony size in a long-lived duck. AB - Anthropogenic impact on the environment and wildlife are multifaceted and far reaching. On a smaller scale, controlling for predators has been increasing the yield from local natural prey resources. Globally, human-induced global warming is expected to impose severe negative effects on ecosystems, an effect that is expected to be even more pronounced in the scarcely populated northern latitudes. The clearest indication of a changing Arctic climate is an increase in both air and ocean temperatures leading to reduced sea ice distribution. Population viability is for long-lived species dependent on adult survival and recruitment. Predation is the main mortality cause in many bird populations, and egg predation is considered the main cause of reproductive failure in many birds. To assess the effect of predation and climate, we compared population time series from a natural experiment where a trapper/down collector has been licensed to actively protect breeding common eiders Somateria mollissima (a large seaduck) by shooting/chasing egg predators, with time series from another eider colony located within a nature reserve with no manipulation of egg predators. We found that actively limiting predator activity led to an increase in the population growth rate and carrying capacity with a factor of 3-4 compared to that found in the control population. We also found that population numbers were higher in years with reduced concentration of spring sea ice. We conclude that there was a large positive impact of human limitation of egg predators, and that this lead to higher population growth rate and a large increase in size of the breeding colony. We also report a positive effect of warming climate in the high arctic as reduced sea-ice concentrations was associated with higher numbers of breeding birds. PMID- 24223291 TI - Ocean acidification and responses to predators: can sensory redundancy reduce the apparent impacts of elevated CO2 on fish? AB - Carbon dioxide (CO2) levels in the atmosphere and surface ocean are rising at an unprecedented rate due to sustained and accelerating anthropogenic CO2 emissions. Previous studies have documented that exposure to elevated CO2 causes impaired antipredator behavior by coral reef fish in response to chemical cues associated with predation. However, whether ocean acidification will impair visual recognition of common predators is currently unknown. This study examined whether sensory compensation in the presence of multiple sensory cues could reduce the impacts of ocean acidification on antipredator responses. When exposed to seawater enriched with levels of CO2 predicted for the end of this century (880 MUatm CO2), prey fish completely lost their response to conspecific alarm cues. While the visual response to a predator was also affected by high CO2, it was not entirely lost. Fish exposed to elevated CO2, spent less time in shelter than current-day controls and did not exhibit antipredator signaling behavior (bobbing) when multiple predator cues were present. They did, however, reduce feeding rate and activity levels to the same level as controls. The results suggest that the response of fish to visual cues may partially compensate for the lack of response to chemical cues. Fish subjected to elevated CO2 levels, and exposed to chemical and visual predation cues simultaneously, responded with the same intensity as controls exposed to visual cues alone. However, these responses were still less than control fish simultaneously exposed to chemical and visual predation cues. Consequently, visual cues improve antipredator behavior of CO2 exposed fish, but do not fully compensate for the loss of response to chemical cues. The reduced ability to correctly respond to a predator will have ramifications for survival in encounters with predators in the field, which could have repercussions for population replenishment in acidified oceans. PMID- 24223292 TI - Quantitative genetic analysis of responses to larval food limitation in a polyphenic butterfly indicates environment- and trait-specific effects. AB - Different components of heritability, including genetic variance (V G), are influenced by environmental conditions. Here, we assessed phenotypic responses of life-history traits to two different developmental conditions, temperature and food limitation. The former represents an environment that defines seasonal polyphenism in our study organism, the tropical butterfly Bicyclus anynana, whereas the latter represents a more unpredictable environment. We quantified heritabilities using restricted maximum likelihood (REML) procedures within an "Information Theoretical" framework in a full-sib design. Whereas development time, pupal mass, and resting metabolic rate showed no genotype-by-environment interaction for genetic variation, for thorax ratio and fat percentage the heritability increased under the cool temperature, dry season environment. Additionally, for fat percentage heritability estimates increased under food limitation. Hence, the traits most intimately related to polyphenism in B. anynana show the most environmental-specific heritabilities as well as some indication of cross-environmental genetic correlations. This may reflect a footprint of natural selection and our future research is aimed to uncover the genes and processes involved in this through studying season and condition dependent gene expression. PMID- 24223293 TI - Multivariate sexual selection on male song structure in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae). AB - While a number of studies have measured multivariate sexual selection acting on sexual signals in wild populations, few have confirmed these findings with experimental manipulation. Sagebrush crickets are ideally suited to such investigations because mating imposes an unambiguous phenotypic marker on males arising from nuptial feeding by females. We quantified sexual selection operating on male song by recording songs of virgin and mated males captured from three wild populations. To determine the extent to which selection on male song is influenced by female preference, we conducted a companion study in which we synthesized male songs and broadcast them to females in choice trials. Multivariate selection analysis revealed a saddle-shaped fitness surface, the highest peak of which corresponded to longer train and pulse durations, and longer intertrain intervals. Longer trains and pulses likely promote greater mate attraction, but selection for longer intertrain durations suggests that energetic constraints may necessitate "time outs". Playback trials confirmed the selection for longer train and pulse durations, and revealed significant stabilizing selection on dominant frequency, suggesting that the female auditory system is tightly tuned to the species-specific call frequency. Collectively, our results revealed a complex pattern of multivariate nonlinear selection characterized primarily by strong stabilizing and disruptive selection on male song traits. PMID- 24223294 TI - Grazer exclusion alters plant spatial organization at multiple scales, increasing diversity. AB - Grazing is one of the most important factors influencing community structure and productivity in natural grasslands. Understanding why and how grazing pressure changes species diversity is essential for the preservation and restoration of biodiversity in grasslands. We use heavily grazed subalpine meadows in the Qinghai-Tibetan Plateau to test the hypothesis that grazer exclusion alters plant diversity by changing inter- and intraspecific species distributions. Using recently developed spatial analyses combined with detailed ramet mapping of entire plant communities (91 species), we show striking differences between grazed and fenced areas that emerged at scales of just one meter. Species richness was similar at very small scales (0.0625 m(2)), but at larger scales diversity in grazed areas fell below 75% of corresponding fenced areas. These differences were explained by differences in spatial distributions; intra- and interspecific associations changed from aggregated at small scales to overdispersed in the fenced plots, but were consistently aggregated in the grazed ones. We conclude that grazing enhanced inter- and intraspecific aggregations and maintained high diversity at small scales, but caused decreased turnover in species at larger scales, resulting in lower species richness. Our study provides strong support to the theoretical prediction that inter- and intraspecific aggregation produces local spatial patterns that scale-up to affect species diversity in a community. It also demonstrates that the impacts of grazing can manifest through this mechanism, lowering diversity by reducing spatial turnover in species. Finally, it highlights the ecological and physiological plant processes that are likely responding to grazing and thereby altering aggregation patterns, providing new insights for monitoring, and mediating the impacts of grazing. PMID- 24223295 TI - Interior Least Tern (Sternula antillarum) breeding distribution and ecology: implications for population-level studies and the evaluation of alternative management strategies on large, regulated rivers. AB - Interior Least Terns (Sternula antillarum) (ILT) are colonial, fish-eating birds that breed within active channels of large sand bed rivers of the Great Plains and in the Lower Mississippi Valley. Multipurpose dams, irrigation structures, and engineered navigation systems have been present on these rivers for many decades. Despite severe alteration of channels and flow regimes, regulation era floods have remained effective at maintaining bare sandbar nesting habitat on many river segments and ILT populations have been stable or expanding since they were listed as endangered in 1985. We used ILT breeding colony locations from 2002 to 2012 and dispersal information to identify 16 populations and 48 subpopulations. More than 90% of ILT and >83% of river km with suitable nesting habitat occur within the two largest populations. However, replicate populations remain throughout the entire historical, geophysical, and ecological range of ILT. Rapid colonization of anthropogenic habitats in areas that were not historically occupied suggests metapopulation dynamics. The highest likelihood of demographic connectivity among ILT populations occurs across the Southern Plains and the Lower Mississippi River, which may be demographically connected with Least Tern populations on the Gulf Coast. Paired ecological and bird population models are needed to test whether previously articulated threats limit ILT population growth and to determine if management intervention is necessary and where. Given current knowledge, the largest sources of model uncertainty will be: (1) uncertainty in relationships between high flow events and subsequent sandbar characteristics and (2) uncertainty regarding the frequency of dispersal among population subunits. We recommend research strategies to reduce these uncertainties. PMID- 24223296 TI - The episodic evolution of fibritin: traces of ancient global environmental alterations may remain in the genomes of T4-like phages. AB - The evolutionary adaptation of bacteriophages to their environment is achieved by alterations of their genomes involving a combination of both point mutations and lateral gene transfer. A phylogenetic analysis of a large set of collar fiber protein (fibritin) loci from diverse T4-like phages indicates that nearly all the modular swapping involving the C-terminal domain of this gene occurred in the distant past and has since ceased. In phage T4, this fibritin domain encodes the sequence that mediates both the attachment of the long tail fibers to the virion and also controls, in an environmentally sensitive way, the phage's ability to infect its host bacteria. Subsequent to its distant period of modular exchange, the evolution of fibritin has proceeded primarily by the slow vertical divergence mechanism. We suggest that ancient and sudden changes in the environment forced the T4-like phages to alter fibritin's mode of action or function. The genome's response to such episodes of rapid environmental change could presumably only be achieved quickly enough by employing the modular evolution mechanism. A phylogenetic analysis of the fibritin locus reveals the possible traces of such events within the T4 superfamily's genomes. PMID- 24223299 TI - Examining the base stacking interaction in a dinucleotide context via reversible cyclobutane dimer analogue formation under UV irradiation. AB - Substituted tolyl groups are considered as close isosteres of the thymine (T) residue. They can be recognized by DNA polymerases as if they were thymine. Although these toluene derivatives are relatively inert toward radical additions, our recent finding suggests that the dinucleotide analogue TpTo (To = 2'-deoxy-1 (3-tolyl)-beta-D-ribofuranose) supports an ortho photocycloaddition reaction upon UV irradiation, producing two cyclobutane pyrimidine dimer (CPD) analogues 2 and 3. Our report here further shows that formation of these CPD species is reversible under UVC irradiation, resembling the photochemical property of the CPD species formed between two Ts. Analyzing the stability of these CPD analogues suggests that one (2) is more stable than the other (3). The TpTo conformer responsible for 2 formation is also more stable than that responsible for 3 formation, as indicated by the Gibbs free energy change calculated from the constructed Bordwell thermodynamic cycle. These different stabilities are not due to the varying photochemical properties, as proved by quantum yields determined from the corresponding photoreactions. Instead, they are ascribed to the different stacking interaction between the T and the To rings both in the TpTo dinucleotide as well as in the formed CPD analogues. Factors contributing to the ring stacking interactions are also discussed. Our proof-of-concept approach suggests that a carefully designed Bordwell cycle coupled with reversible CPD formations under UV irradiation can be very useful in studying DNA base interactions. PMID- 24223300 TI - Vascular tortuosities of the upper eyelid: a new clinical finding in fabry patient screening. AB - Purpose. To report a new clinical finding related to Fabry disease. Methods. Fabry subjects were enrolled in the study, matched for age and sex with healthy individuals as a control group. This is a prospective review of all upper lid pictures taken for every subject at their last visit. A 4-step grading scale is proposed to classify this new entity. Results. Group A (Fabry) comprised 16 males and 22 females, aged 40 (+/-14) years on average. Group B (control) comprised 7 males and 8 females, aged 37 (+/-12) Vessels tortuosity was identified on the external superior lid in 36 of the Fabry patients (94.7%), while none of the subjects in group B showed similar vessels tortuosity. In addition, microaneurysms (MAs) were found in 10/38 group A subjects while none in group B presented a similar finding. The differences are highly significant. Conclusion. This paper proposes that blood vessels tortuosity on the upper eyelid be recognized as a new clinical entity for inclusion among the classic ocular manifestations of Fabry's disease. Without evidence of any negative impact, it should be considered a benign sign contributing to evidence of suspected Fabry disease. PMID- 24223301 TI - Lamellar keratoplasty: a literature review. AB - The concept of lamellar keratoplasty (LK) is not new. However, newer forms of lamellar keratoplasty techniques have emerged in the last decade or so revolving around the concept of targeted replacement of diseased corneal layers. These include anterior lamellar keratoplasty (ALK) techniques that aim to selectively replace diseased corneal stroma and endothelial keratoplasty techniques aiming to replaced damaged endothelium in endothelial disorders. Recent improvements in surgical instruments and introduction of new techniques as well as inherent advantages such as preservation of globe integrity and decreased graft rejection have resulted in the reintroduction of LK as an acceptable alternative to conventional PK. In this review, indications, benefits, limitations, and outcomes of various anterior and posterior lamellar keratoplasty techniques are discussed. PMID- 24223302 TI - Relationship between Plasma Aldosterone Levels and Left Ventricular Mass in Hypertensive Africans. AB - Background. Hypertension is the most common cardiovascular disease worldwide and is a major cause of morbidity and mortality. Studies have suggested that the activity of the renin-angiotensin-aldosterone system play a major role in the target organ damage such as left ventricular hypertrophy occuring in hypertension. We sought to determine the relationship between plasma aldosterone and left ventricular mass in untreated African hypertensives. Methods. We recruited 82 newly diagnosed and untreated hypertensives and 51 normal controls. Measurements obtained included echocardiographic LV mass index, plasma aldosterone and renin. Results. The hypertensive subjects had lower renin levels (21.03[6.974] versus 26.66[7.592] ng.mL(-1), P = 0.0013), higher LV mass index (52.56[14.483] versus 42.02[8.315] g.m(-2.7) P < 0.0001) when compared with the controls. There were no univariate associations between LV mass index and plasma aldosterone (r = 0.0179, P = 0.57) and between LV mass index and plasma renin (r = 0.0887, P = 0.61). In a multivariate model involving LV mass index and age, sex, body mass index (BMI), plasma aldosterone, plasma renin and systolic blood pressure (SBP), only age (P = 0.008), BMI (P = 0.046), and SBP (P = 0.001) were independently associated with the LV mass index. Conclusions. In this group of hypertensive Africans, there is no independent association of plasma aldosterone with LV mass. The height of the blood pressure, the body mass index and the age of the subjects determined the LV mass. PMID- 24223303 TI - Measuring the response of extrahepatic symptoms and quality of life to antiviral treatment in patients with hepatitis C. AB - Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon- alpha and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, P = 0.015). Sicca syndrome prevalence fell insignificantly (12.7% versus 11%). SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients. PMID- 24223304 TI - Trail overexpression inversely correlates with histological differentiation in intestinal-type sinonasal adenocarcinoma. AB - INTRODUCTION: Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure. MATERIAL AND METHODS: Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results. RESULTS: The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses. CONCLUSION: The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC. PMID- 24223305 TI - Cardiovascular disease self-care interventions. AB - Background. Cardiovascular disease (CVD) is a major cause of increased morbidity and mortality globally. Clinical practice guidelines recommend that individuals with CVD are routinely instructed to engage in self-care including diet restrictions, medication adherence, and symptom monitoring. Objectives. To describe the nature of nurse-led CVD self-care interventions, identify limitations in current nurse-led CVD self-care interventions, and make recommendations for addressing them in future research. Design. Integrative review of nurse-led CVD self-care intervention studies from PubMed, MEDLINE, ISI Web of Science, and CINAHL. Primary studies (n = 34) that met the inclusion criteria of nurse-led RCT or quasiexperimental CVD self-care intervention studies (years 2000 to 2012) were retained and appraised. Quality of the review was assured by having at least two reviewers screen and extract all data. Results. A variety of self-care intervention strategies were studied among the male (57%) and Caucasian (67%) dominated samples. Combined interventions were common, and quality of life was the most frequent outcome evaluated. Effectiveness of interventions was inconclusive, and in general results were not sustained over time. Conclusions. Research is needed to develop and test tailored and inclusive CVD self-care interventions. Attention to rigorous study designs and methods including consistent outcomes and measurement is essential. PMID- 24223306 TI - Optic neuritis as isolated manifestation of leptomeningeal carcinomatosis: a case report and systematic review of ocular manifestations of neoplastic meningitis. AB - Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52 year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83%) out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%). Visual loss was the presenting clinical manifestation in 17 patients (50%) and was the most common ocular symptom (70%). Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%). Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms. PMID- 24223307 TI - The Association between Seasonal Variation in Vitamin D, Postural Sway, and Falls Risk: An Observational Cohort Study. AB - Introduction. Low serum vitamin D levels are associated with increased postural sway. Vitamin D varies seasonally. This study investigates whether postural sway varies seasonally and is associated with serum vitamin D and falls. Methods. In a longitudinal observational study, eighty-eight independently mobile community dwelling older adults (69.7 +/- 7.6 years) were evaluated on five occasions over one year, measuring postural sway (force platform), vitamin D levels, fall incidence, and causes and adverse outcomes. Mixed-methods Poisson regression was used to determine associations between measures. Results. Postural sway did not vary over the year. Vitamin D levels varied seasonally (P < 0.001), peaking in summer. Incidence of falls (P = 0.01) and injurious falls (P = 0.02) were lower in spring, with the highest fall rate at the end of autumn. Postural sway was not related to vitamin D (P = 0.87) or fall rates, but it was associated with fall injuries (IRR 1.59 (CI 1.14 to 2.24, P = 0.007). Conclusions. Postural sway remained stable across the year while vitamin D varied seasonally. Participants with high values for postural sway demonstrated higher rates of injurious falls. This study provides important evidence for clinicians and researchers providing interventions measuring balance outcomes across seasons. PMID- 24223308 TI - Effects of walking direction and cognitive challenges on gait in persons with multiple sclerosis. AB - Declines in walking performance are commonly seen when undergoing a concurrent cognitive task in persons with multiple sclerosis (MS). The purpose of this study was to determine the effect of walking direction and simultaneous cognitive task on the spatiotemporal gait parameters in persons with MS compared to healthy controls. Ten persons with MS (Median EDSS, 3.0) and ten healthy controls took part in this pilot study. Participants performed 4 walking trials at their self selected comfortable pace. These trials included forward walking, forward walking with a cognitive task, backward walking, and backward walking with a cognitive task. Walking performance was indexed with measures of velocity, cadence, and stride length for each testing condition. The MS group walked slower with significantly reduced stride length compared to the control group. The novel observation of this investigation was that walking differences between persons with MS and healthy controls were greater during backward walking, and this effect was further highlighted during backward walking with added cognitive test. This raises the possibility that backward walking tests could be an effective way to examine walking difficulties in individuals with MS with relatively minimal walking impairment. PMID- 24223310 TI - A study on evaluation of apoptosis and expression of bcl-2-related marker in wound healing of streptozotocin-induced diabetic rats. AB - Uncontrolled blood sugar is a major cause of vascular complications and delayed wound healing in diabetes mellitus. During wound healing process, normally, apoptosis is responsible for events such as removal of inflammatory cells and evolution of granulation tissue into scar which occur during the late phase of wound healing. Early apoptosis can lead to abnormal wound healing by removing granulation tissue including fibroblast, endothelial cell, and small vessels. To determine the role of apoptosis in association with hyperglycemia in diabetic wound healing, apoptosis-related intracellular marker such as expression of Bcl-2 protein by immunohistochemistry and normal histology has been studied. Histological findings show higher level of apoptosis and diminished granulation tissue formation in diabetic rats wounds along with minimal expression of Bcl-2 in diabetic rats wounds when compared with nondiabetic rats wounds. It can be concluded from this study that elevated blood sugar level may be associated with increased apoptosis and the least expression of Bcl-2 protein which might cause deregulation of the wound healing processes in streptozotocin-induced diabetic rats. PMID- 24223309 TI - Pretreatment of Small-for-Size Grafts In Vivo by gamma -Aminobutyric Acid Receptor Regulation against Oxidative Stress-Induced Injury in Rat Split Orthotopic Liver Transplantation. AB - Background. Graft pretreatment to limit postoperative damage has the advantage of overcoming a current issue in liver transplantation (LT). The strategic potential of graft pretreatment in vivo by a specific agonist for gamma -aminobutyric acid receptor (GABAR) was investigated in the rat LT model with a small-for-size graft (SFSG). Methods. Recipient rats were divided into three groups according to donor treatments and recipient surgeries: (i) saline and laparotomy, (ii) saline and split orthotopic liver transplantation (SOLT) with 40%-SFSG, and (iii) GABAR agonist and SOLT with 40%-SFSG. Survival was evaluated. Blood and liver samples were collected 6 h after surgery. Immunohistological assessment for apoptotic induction and western blotting for 4-hydroxynonenal, ataxia-telangiectasia mutated kinase (ATM), histone H2AX, phosphatidylinositol-3 kinase (PI3K), Akt, and free radical scavenging enzymes were performed. Results. Pretreatment by GABAR showed improvement in survival, histopathological assessment, and biochemical tests. Apoptotic induction and oxidative stress were observed after SOLT with an SFSG, and this damage was limited by GABAR regulation. GABAR regulation appeared to reduce DNA damage via the ATM/H2AX pathway and to promote cell survival via the PI3K/Akt pathway. Conclusions. Pretreatment in vivo by GABAR regulation improves graft damage after SOLT with an SFSG. This strategy may be advantageous in LT. PMID- 24223311 TI - The Practice of Medical Oncology in Morocco: The National Study of the Moroccan Group of Trialist in Medical Oncology (EVA-Onco). AB - Objective. To determine the current shortfall of medical oncologists (MOs) and the projected supply. Background. Morocco, the medical oncology (MO) is a relatively new specialty. Medical oncology was recognized as a separate specialty in 1994 but the real taking-off was done only since the 2000s after the creation of the chair of medical oncology in the University of Rabat. The GRIOMM (Moroccan group of trialist in medical oncology) was created in 2011 and conducted its first study, EVA-onco, concerning the practice of medical oncology in Morocco in 2011. Design. EVA-onco is a prospective study concerning the practice of medical oncology in Morocco in 2011. Results. The entire public cancer centers completed the survey. There were no missing data. The number of medical oncologist per 100000/habitants in Morocco was 0.09. The average number of new patients seen per medical oncologist was 718 patients (ranging by state from 97 to 1875). The shortfall of MOs was estimated at 26 at least in 2011 according to the national recommendations. Conclusions. Since 2010, a national strategy to increase the capacity of MO workforce existed. The current shortfall of MO is expected to disappear in the future. PMID- 24223312 TI - Antileukemic Efficacy of Monomeric Manganese-Based Metal Complex on KG-1A and K562 Cell Lines. AB - Transitional metals and metal compounds have been used in versatile platforms for biomedical applications and therapeutic intervention. Severe side effects of anticancer drugs produce an urgent urge to develop new classes of anticancer agents with great potency as well as selectivity. In this background, recent studies demonstrate that monomeric manganese (MnII) thiocyanate complex (MMTC) holds great promise to exert effective antileukemic effects. MMTC was developed by a simple chemical reaction and characterized by elemental analyses, thermal analyses, and Fourier transform infrared (FTIR) spectroscopy. Anti-leukemic efficacy of the developed MMTC was estimated in KG-1A (AML) and K562 (CML) cell lines. Cell viability study, drug uptake assay, cellular redox balance (GSH and GSSG level), nitric oxide (NO) release level, reactive oxygen species (ROS) formation, alteration of mitochondrial membrane potential (MMP), and DNA fragmentation revealed that MMTC was able to produce significant antiproliferative effects on both cell lines at 25 MU g mL(-1) without showing any toxicological impact on normal lymphocytes. These findings will enlighten the biomedical application of manganese-based metal complexes as anti-leukemic agents. PMID- 24223313 TI - Influence of body position on severity of obstructive sleep apnea: a systematic review. AB - Aim. The aim of this review is to determine the relationship between sleeping body posture and severity of obstructive sleep apnea. This relationship has been investigated in the past. However, the conclusions derived from some of these studies are conflicting with each other. This paper intends to summarize the reported relationships between sleep posture and various sleep indices in patients diagnosed with sleep apnea. Methods and Materials. A systematic review of the published English literature during a 25-year period from 1983 to 2008 was performed. Results. Published data concerning the sleep apnea severity and posture in adults are limited. Supine sleep posture is consistently associated with more severe obstructive sleep apnea indices in adults. However, relationship between sleep apnea severity indices and prone posture is inconsistent. PMID- 24223314 TI - A massive posterior neck mass: lipoma or something more sinister? AB - Lipomas are slow-growing benign soft-tissue tumors which are typically asymptomatic and occur in approximately 1% of the population. A lipoma is considered to be of excessive size when it is greater than 10 cm in length (in any dimension) or weighs over 1000 g (Kransdorf (1995)). We describe a case of a man presenting with a giant posterior neck mass which greatly reduced the sagittal range of cervical spine. A discussion of the pathophysiology of lipomas and a literature review regarding giant lipomas versus malignancy follows. PMID- 24223315 TI - Acute on chronic venous thromboembolism on therapeutic anticoagulation. AB - A case of proximal venous thromboembolism in a patient who presented to the ED with lower extremity pain is presented. Making this diagnosis is very important as fifty percent of patients with symptomatic proximal DVTs will go on to develop PE without treatment. This report underscores the utility of bedside ultrasonography in the emergency department. PMID- 24223316 TI - Candida albicans Fungaemia following Traumatic Urethral Catheterisation in a Paraplegic Patient with Diabetes Mellitus and Candiduria Treated by Caspofungin. AB - A 58-year-old paraplegic male, with long-term indwelling urethral catheter, developed catheter block. The catheter was changed, but blood-stained urine was drained intermittently. A long segment of the catheter was seen lying outside his penis, which indicated that the balloon of Foley catheter had been inflated in urethra. The misplaced catheter was removed and a new catheter was inserted correctly. Gentamicin 160 mg was given intravenously; meropenem 1 gram every eight hours was prescribed; antifungals were not given. Twenty hours later, this patient developed distension of abdomen, tachycardia, and hypotension; he was not arousable. Computed tomography of abdomen revealed inflamed uroepithelium of right renal pelvis and ureter, 4 mm lower ureteric calculus with gas in right ureter proximally, and vesical calculus containing gas in its matrix. Urine and blood culture yielded Candida albicans. Identical sensitivity pattern of both isolates suggested that the source of the bloodstream infection was most likely urine. Both isolates formed consistently high levels of biofilm formation in vitro as assessed using a biofilm biomass stain, and high levels of resistance to voriconazole were observed. Both amphotericin B and caspofungin showed good activity against the biofilms. HbA1c was 111 mmol/mol. This patient was prescribed human soluble insulin and caspofungin 70 mg followed by 50 mg daily intravenously. He recovered fully from candidemia. PMID- 24223317 TI - Treatment of palatal myoclonus with botulinum toxin injection. AB - Palatal myoclonus is a rare cause of pulsatile tinnitus in patients presenting to the otolaryngology office. Rhythmic involuntary contractions of the palatal muscles produce the pulsatile tinnitus in these patients. Treatment of this benign but distressing condition with anxiolytics, anticonvulsants, and surgery has been largely unsuccessful. A few investigators have obtained promising results with botulinum toxin injection into the palatal muscles. We present a patient with palatal myoclonus who failed conservative treatment with anxiolytics. Unilateral injection of botulinum toxin into her tensor veli palatini muscle under electromyographic guidance resolved pulsatile tinnitus in her ipsilateral ear and unmasked pulsatile tinnitus in the contralateral ear. A novel method of following transient postinjection symptoms using a diary is presented in this study. Botulinum toxin dose must be titrated to achieve optimal results in each individual patient, analogous to titrations done for spasmodic dysphonia. Knowledge of the temporal onset of postinjection side effects and symptomatic relief may aid physicians in dose titration and surveillance. We present suggestions on titrating the botulinum toxin dose to optimal levels. A review of the literature on the use of botulinum toxin for palatal myoclonus and some common complications are discussed. PMID- 24223318 TI - Intrauterine upper limb ischemia: an unusual presentation of fetal thrombophilia a case report and review of the literature. AB - Upper limb ischemia presenting in neonatal period is extremely rare. Moreover, presenting newborn with evidence of intrauterine upper limb vascular occlusion is even rarer. It needs prompt intervention to restore perfusion and avoid morbidity. We present a newborn with right upper limb brachial artery thrombosis causing ischemia that was noted at birth and appeared later to be homozygous for factor V Leiden and glycoprotein IIIa with no other identifiable risk factors. In this report, we present the case, its successful medical management, proper counseling, and review of the literature. We recommend investigating the neonates and their parents for thrombophilia mutations when they present with unusual vascular occlusion site as newborns. PMID- 24223319 TI - Large conization and laparoendoscopic single-port pelvic lymphadenectomy in early stage cervical cancer for fertility preservation. AB - Fertility preservation in early-stage cervical cancer is a hot topic in gynecologic oncology. Although radical vaginal trachelectomy (RVT) is suggested as a fertility preserving approach, there are some serious concerns like cervical stenosis, second trimester loss, preterm delivery in survivors, and lack of residual tumor in the majority of the surgical specimens. Therefore, less radical surgical operations have been proposed in early-stage cervical carcinomas. On the other hand, single-incision laparoscopic surgery (SILS) is an evolving endoscopic approach for minimal access surgery. In this report, we present a case with early stage cervical cancer who wishes to preserve fertility. We successfully performed single-port pelvic lymphadenectomy and large conization to preserve fertility potential of the patient. We think that combination of less radical approach like conization and single-port pelvic lymphadenectomy might be less minimally invasive and is still an effective surgical approach in well-selected cases with cervical carcinomas. Incorporation of single-port laparoscopy into the minimally invasive fertility sparing management of the cervical cancer will improve patients outcome with less complications and better cosmesis. Further studies are needed to reach a clear conclusion. PMID- 24223320 TI - Hepatic portal venous gas: comparison of two cases. AB - Context. Hepatic portal venous gas (HPVG) is a rare and sinister finding. Its mortality is associated with the underlying causative condition. When secondary to bowel ischaemia, mortality rates exceed 50%. Case Report. Two cases of HPVG are described. One case describes HPVG in association with gastric ischaemia, with complete resolution following conservative management. The second case describes HPVG in association with widespread intra-abdominal ischaemia, with resultant mortality. Conclusion. A "watch and wait" management of HPVG associated with gastric ischaemia is suggested in certain patients, with a low threshold for surgical intervention. HPVG associated with bowel ischaemia is an absolute indication for surgical intervention, where intervention may change the clinical course. PMID- 24223321 TI - Why hospital pharmacists have failed to manage antimalarial drugs stock-outs in pakistan? A qualitative insight. AB - Purpose. This study aimed to explore the perceptions of hospital pharmacists towards drug management and reasons underlying stock-outs of antimalarial drugs in Pakistan. Methods. A qualitative study was designed to explore the perceptions of hospital pharmacists regarding drug management and irrational use of antimalarial drugs in two major cities of Pakistan, namely, Islamabad (national capital) and Rawalpindi (twin city). Semistructured interviews were conducted with 16 hospital pharmacists using indepth interview guides at a place and time convenient for the respondents. Interviews, which were audiotaped and transcribed verbatim, were evaluated by thematic content analysis and by other authors' analysis. Results. Most of the respondents were of the view that financial constraints, inappropriate drug management, and inadequate funding were the factors contributing toward the problem of antimalarial drug stock-outs in healthcare facilities of Pakistan. The pharmacists anticipated that prescribing by nonproprietary names, training of health professionals, accepted role of hospital pharmacist in drug management, implementation of essential drug list and standard treatment guidelines for malaria in the healthcare system can minimize the problem of drug stock outs in healthcare system of Pakistan. Conclusion. The current study showed that all the respondents in the two cities agreed that hospital pharmacist has failed to play an effective role in efficient management of anti-malarial drugs stock-outs. PMID- 24223322 TI - The use of 7,7',8,8'-tetracyanoquinodimethane for the spectrophotometric determination of some primary amines application to real water samples. AB - A sensitive, simple, and accurate spectrophotometric method was developed for the quantitative determination of some primary aliphatic and aromatic amines, that is, ethylamine, 1,2-diaminopropane, aniline, p-aminophenol, and benzidine. The method is based on the interaction of these amines in aqueous medium with 7,7',8,8'-tetracyanoquinodimethane (TCNQ) reagent in the presence of a buffer solution and surfactant (in the case of aromatic amines) to form charge-transfer complexes measurable at maximum wavelengths ranging between 323 and 511 nm. Beer's law is obeyed over the concentration ranges of 0.025 and 3.0 MU g/mL and the molar absorptivity is ranged between 8.977 * 10(3) and 5.8034 * 10(4) L . mol(-1) . cm(-1) for these amines. The method was applied for the determination of benzidine in the river, sea, and tap waters. The TCNQ complexes with the previously mentioned amines were formed in the ratio of 1 : 1 amine : TCNQ, and their stability constants ranged between 8.78 * 10(4) and 1.844 * 10(5) L . mol( 1). PMID- 24223324 TI - The potential role of regional anesthesia in perioperative anti-inflammatory treatments. PMID- 24223323 TI - Acute Heart Failure Treatment. AB - Dyspnea is the predominant symptom for patients with acute heart failure and initial treatment is largely directed towards the alleviation of this. Contrary to conventional belief, not all patients present with fluid overload and the approach to management is rapidly evolving from a solitary focus on diuresis to one that more accurately reflects the complex interplay of underlying cardiac dysfunction and acute precipitant. Effective treatment thus requires an understanding of divergent patient profiles and an appreciation of various therapeutic options for targeted patient stabilization. The key principle within this paradigm is directed management that aims to diminish the work of breathing through situation appropriate ventillatory support, volume reduction and hemodynamic improvement. With such an approach, clinicians can more efficiently address respiratory discomfort while reducing the likelihood of avoidable harm. PMID- 24223325 TI - Understanding cervicogenic headache. AB - The purported mechanism underlying the development and progression of cervicogenic headache (CEH) is the convergence of sensory inputs at the trigeminocervical nucleus. This mechanism explains the radiation of pain from the neck or the occipitonuchal area and its spread to the oculo-fronto-temporal region; it also explains the recurrent headaches caused by improper neck postures or external pressure to the structures in the neck and the occipital region. These neural connectivity mechanisms involving the trigeminal nucleus are also evident from the eyeblink reflex and findings of quantitative sensory testing (QST). Understanding the mechanisms underlying the development of CEH is important because it will not only provide a better treatment outcome but will also allow practitioners to appreciate the variability of symptomatic presentations in these patients. PMID- 24223326 TI - Beyond Beauty: Onobotulinumtoxin A (BOTOX(r)) and the Management of Migraine Headaches. AB - Based on the conducted anatomic studies at our institutions as well as clinical experience with migraine surgery, we have refined our onobotulinumtoxin A (BOTOX(r)) injection techniques. Pain management physicians are in unique position to be able to not only treat migraine patient, but also to be able to collaborate with neurologists and peripheral nerve surgeons in identifying the migraine trigger sites prior to surgical deactivation. The constellation of migraine symptoms that aid in identifying the migraine trigger sites, the potential pathophysiology of each trigger site, the effective methods of botulinumtoxin and nerve block injection for diagnostic and treatment purposes, as well as the pitfalls and potential complications, will be addressed and discussed in this paper. PMID- 24223327 TI - Effect of oral pregabalin premedication on post-operative pain in laparoscopic gastric bypass surgery. AB - BACKGROUND: Post-operative pain and the administration of opioids to relieve it, is considered to be one of the important issues in surgery wards. This issue is even more significant in obese patients, because of the side effects of opioids. Pregabalin is an analog of gamma aminobutyric acid (GABA) which can be effective in dealing with post-operative pain. OBJECTIVES: This study will consider the effect of oral pregabalin in relieving the pain of obese patients after gastric bypass surgery. PATIENTS AND METHODS: In a double blind clinical trial, 60 candidates for laparoscopic gastric bypass surgery were enrolled in the study through convenience and non-random sequential sampling, into two groups; pregabalin group and control group. Inclusion criteria consisted of: morbid obesity with a body mass index (BMI) > 35, age 18-50, American Society of Anesthesiologists (ASA) status I or II, and willingness to take part in the study. Patients in the pregabalin group received 300 mg of oral pregabalin on the morning of the surgery. Post-operative pain was controlled by the patient controlled intravenous analgesia (PCIA) method, an AutoMed infusion pump containing 20 mg of morphine and normal saline (total volume 100 cc) was administered to all patients after surgery. Patients' level of pain were compared by considering their pain intensity on a visual analog scale (VAS), and the occurrence of nausea/vomiting from recovery, until 24 hours after surgery. RESULTS: A total of 60 patients were compared; 30 patients in each of the pregabalin and control groups. Both groups were similar in age and sex distribution. Mean pain intensity levels during the whole follow up were lower in the pregabalin group than in the control group, up to a maximum of 24 hours after the operation (P < 0.001). Incidence of nausea/vomiting was greater in the control group than in the pregabalin group (P < 0.001). CONCLUSIONS: The findings of this study indicate that oral pregabalin (300 mg dose) can alleviate patients' pain and nausea/vomiting and notably reduce adverse effects. PMID- 24223328 TI - Comparison between effect of lidocaine, morphine and ketamine spray on post tonsillectomy pain in children. AB - BACKGROUND: An effective pain therapy to block or modify the physiological responses to stress has become an essential component of modern pediatric anesthesia and surgical practice. OBJECTIVES: The goal of this study was to compare the analgesic effects of the spray forms of; lidocaine, morphine, ketamine, and normal saline on post-tonsillectomy pain scores in children. PATIENTS AND METHODS: A total of 120 children, American Society of Anesthesiologist (ASA) class I-II, scheduled for elective tonsillectomy were enrolled in this double-blind, clinical trial study. They were randomly divided into 4 groups, each receiving one of the following drugs at the end of operation; lidocaine spray (2 mg/kg); morphine spray (0.05 mg/kg); ketamine spray (0.5 mg/kg); or normal saline spray (8 puffs). For comparison of postoperative pain; the face, legs, activity, cry, consolability (FLACC) pain scale was evaluated during the first one hour of recovery period at 20 minutes intervals. The data was transferred to SPSS-10 software and analyzed statistically with the Scheffe test and Dunnett's T3 test. P value less than 0.05 was considered significant. RESULTS: IN THE EARLY POSTOPERATIVE PERIOD (TIME: 0) and at 20, 40 and 60 minutes of recovery time, FLACC scale scores in the control group were higher than in the three other groups. At 20 minutes, the FLACC scale score in the lidocaine group was lower than in the other groups. At 40 minutes, the statistical differences between FLACC scales of the lidocaine, morphine and ketamine groups were not significant (P > 0.05). Finally, at 60 minutes, the FLACC scale scores of the ketamine and morphine groups were lower than in the other groups. CONCLUSIONS: The results of this study showed that lidocaine spray had the best pain controlling effect at 20 minutes in the recovery room, but after 40 minutes, ketamine and morphine sprays were more effective than the lidocaine spray. PMID- 24223329 TI - Does analgesic effect of opium hamper the adverse effects of severe coronary artery disease on quality of life in addicted patients? AB - BACKGROUND: Opium is a unique substance, regarding its analgesic effects. This may change the deteriorating effects of coronary artery disease (CAD) on quality of life (QOL) in addicted patients. OBJECTIVES: We studied the QOL in opium addicted and non-addicted CAD patients so as to determine the relationship between CAD risk factors and the subscales of their QOL. PATIENTS AND METHODS: Demographic and laboratory data as well as coronary artery risk factors were obtained and SF-36 questionnaire was completed through interviews with 268 (38 opium-addicted and 230 non-addicted) patients with CAD who were candidates for isolated coronary artery bypass at Tehran Heart Center. RESULTS: Mean Euro SCORE in addicted and non-addicted patients were 3.7 +/- 7.6 and 2.4 +/- 2.2 respectively (P = 0.036). In addicted group, higher preoperative HbA1c was associated with low physical function score (beta = -0.395, P = 0.021). Low ejection fraction could negatively affect the general health (beta = 0.394, P = 0.014) and mental health (beta = 0.292, P = 0.015) subscales in the addicted group. CONCLUSIONS: Despite higher rate of morbidities in opium-addicted patients compared to non-addicted ones, subscales of QOL were similar between the two groups. High preoperative HbA1c and low ejection fraction appeared to be determinants of poor QOL in the opium-addicted patients. PMID- 24223330 TI - Comparing the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery. AB - BACKGROUND: Intra-articular analgesia is a pain reliever that is frequently administered following arthroscopic knee surgery. OBJECTIVES: The purpose of this study was to compare the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery. PATIENTS AND METHODS: For this randomized double blinded clinical trial, 132 patients undergoing minor arthroscopic knee surgery were randomly assigned to receive either; 5 mg morphine or 50 mg tramadol intra-articularly. Pain was evaluated by means of the verbal pain rating score (VRS) preoperatively (at rest and on movement of the knee joint) and postoperatively at 0, 1, 2, 3, 4, 6, 12 and 24 hours. Meanwhile, the time of the first analgesic request and need for supplemental analgesic were also recorded. RESULTS: There was no statistically significant difference in VRS scoring between the two groups during the preoperative period either at rest or on knee movement. Meanwhile, VRS scores did not differ significantly between the morphine and tramadol treated groups postoperatively, except for in the one-hour post-operative scores in which the tramadol-treated group experienced less pain (P < 0.007). Post-operative VRS scores at 6, 12, and 24 hours were significantly decreased when compared with previous scores in both morphine and tramadol prescribed subjects (P < 0.001), hence, both local analgesics can significantly reduce pain after minor knee surgery. CONCLUSIONS: We have found a postoperative analgesic effect of intra articularly administered morphine and tramadol following minor arthroscopic knee surgeries with a maximum effect 6 hours post injection. PMID- 24223331 TI - Comparison of combined femoral nerve block and spinal anesthesia with lumbar plexus block for postoperative analgesia in intertrochanteric fracture surgery. AB - BACKGROUND: Hip fracture-related pain both before and after surgery is generally reported as severe by most patients. Various regional pain control modalities have been described in order to reduce pain in these patients. OBJECTIVES: Because of the challenges of lumbar plexus block (LPB) and the fact that the effect of combined femoral nerve block/spinal anesthesia in controlling pain after orthopedic surgeries has not been investigated, in this study, we compared the feasibility and efficacy of the 2 techniques in the perioperative management of proximal hip fractures. PATIENTS AND METHODS: The study included 32 patients with femoral intertrochanteric fracture who were randomly divided into the following 2 groups of 16 patients each: combined femoral nerve block/spinal anesthesia group (group I) and LPB group (group II). Patients in group I received 0.17% bupivacaine with 0.7% lidocaine, 20-25 mL for femoral nerve block and bupivacaine 0.5% plus 0.5 mL pethidine (25 mg) for spinal block and patients in group II received 0.17% bupivacaine with 0.7% lidocaine, 30-35 mL. RESULTS: The time for performing the block (12.2 +/- 3.3 vs. 4.93 +/- 1.6 min, P = 0.001) and achieving the block (7.7 +/- 0.9 vs. 2.4 +/- 1.0 min, P = 0.001) were significantly longer in the combined femoral nerve block/spinal anesthesia group than in the LPB group. Duration of analgesia in the combined femoral nerve block/spinal anesthesia group was longer than that in the LPB group, but the difference was not significant (17 +/- 7.3 vs. 16.5 +/- 8.5 h, P = 0.873). There were no significant differences in hemodynamic parameters regarding the method of anesthesia in the 2 groups. CONCLUSIONS: This study confirms that the combination of femoral nerve block with spinal anesthesia is safe and comparable with LPB and can provide more effective anesthesia and longer lasting analgesia for intertrochanteric surgery. PMID- 24223332 TI - Interspinous process implantation for the treatment of neurogenic intermittent claudication. AB - BACKGROUND: Lumbar spinal stenosis (LSS) is a disabling medical condition in which narrowing of the spinal canal compresses the spinal cord and nerves causing a condition called neurogenic intermittent claudication (NIC). Decompressive spine surgery is the standard of care for patients who fail to improve with conservative management. However, oftentimes, patients who suffer from LSS are elderly individuals with multiple co-morbidities who cannot withstand the risks of decompressive surgery. X-Stop, a novel and minimally invasive FDA approved interspinous process implant, has come into the scene as an alternative to decompressive surgery, and can be inserted under local anesthetic with minimal blood loss. OBJECTIVES: Despite its growing support in medical literature as an effective and conservative treatment of NIC, X-Stop remains a fairly new form of treatment. The aim of this study is to assess the clinical efficacy of its use. PATIENTS AND METHODS: Fifty consecutive patients with at least two-year follow-up had a confirmed diagnosis of NIC secondary to LSS by computed tomography or magnetic resonance imaging (MRI) and subsequently received an X-Stop implant. Subjects' ages ranged from 64 to 95 with a mean age of 79, while the gender distribution comprised of 23 males and 27 females. Zurich Claudication Questionnaire (ZCQ) was used to assess patient outcome measures in three domains: physical function (PF), patient satisfaction (PS), and symptom severity (SS). The visual analog scale (VAS) was used to assess trends in pain with a scale from 0 10, with 0 defined as "pain-free" and 10 designated as "the worst pain imaginable". RESULTS: Compared to pre-op scores, PF, SS, and VAS scores for back, buttock and leg pain had a significant mean decrease at 6, 12, 24 months post-op (P < 0.05). Based on the ZCQ and VAS scores, a success rate of 79% (27.34), 78% (30.38) and 74% (17.23) were achieved at six months, 12 months, and 24 months respectively. CONCLUSIONS: X-Stop is a safe and effective treatment for NIC that provides marked relief of symptoms with sustained beneficial outcomes at up to two years of follow-up. In addition, X-Stop permits implantation under local anesthetic with minimal blood loss". PMID- 24223333 TI - Management of painful vertebral compression fracture with kyphoplasty in a sever cardio-respiratory compromised patient. AB - INTRODUCTION: Vertebral body compression fractures due to osteoporosis, often lead to pain and disability which can be successfully treated by injecting cement into the vertebral body, a procedure known as Balloon Kyphoplasty. In this procedure, an inflatable balloon is used to restore vertebral body height before injection of the cement. Vertebral compression fractures have been treated conservatively with the bed rest, pain medications, and back bracing to decrease the patient's pain, but the spine was left in its deformed state. Open surgical treatment can address the deformity, but it is usually reserved for patients with a neurological deficit. Kyphoplasty have been developed as an alternative to surgery for the treatment of painful vertebral compression fractures. CASE PRESENTATION: A 65 year-old female had a compression fracture and decrease height of L1 due to falling down. She had a local severe pain (VAS 8) and tenderness over L1 to L4 vertebra and in her physical examination, there were not any neurologic deficits or bowel and bladder dysfunction. She had a severe cardiovascular disease with low ejection fraction (30%) and had a pace maker, hypertension, diabetes, Chronic obstructive pulmonary disease (COPD), and used about 15 drugs daily. The risk of anesthesia and open surgery was high, therefore she was nominated for the Balloon Kyphoplasty as an interventional procedure. CONCLUSIONS: After Kyphoplasty, her pain was immediately resolved, vertebral body height was restored to normal, and pain score was reduced from 8 to 1. She was discharged with a normal neurological examination and good general condition, and returned to her normal life. In this case, Balloon Kyphoplasty resulted in the restoration of the vertebral body height, decrease in pain, and returning to daily activity. Therefore, this technique can be an appropriate alternative for surgery in cardio-pulmonary compromised patients. PMID- 24223334 TI - Pain lateralization in trigeminal neuralgia. PMID- 24223335 TI - Commentary on: Effects of Lumbar Discectomy on Disability and Depression in Patients With Chronic Low-Back Pain. PMID- 24223336 TI - Tracheal intubation without the use of neuromuscular blocking agents. PMID- 24223337 TI - Gabapentinoids: gabapentin and pregabalin for postoperative pain management. PMID- 24223338 TI - Rethinking the psychogenic model of complex regional pain syndrome: somatoform disorders and complex regional pain syndrome. AB - ABSTRACT: Explaining the etiology of Complex Regional Pain Syndrome (CRPS) from the psychogenic model is exceedingly unsophisticated, because neurocognitive deficits, neuroanatomical abnormalities, and distortions in cognitive mapping are features of CRPS pathology. More importantly, many people who have developed CRPS have no history of mental illness. The psychogenic model offers comfort to physicians and mental health practitioners (MHPs) who have difficulty understanding pain maintained by newly uncovered neuro inflammatory processes. With increased education about CRPS through a biopsychosocial perspective, both physicians and MHPs can better diagnose, treat, and manage CRPS symptomatology. PMID- 24223339 TI - Risk factors for postoperative respiratory mortality and morbidity in patients undergoing coronary artery bypass grafting. AB - ABSTRACT: Nowadays, coronary artery bypass grafting (CABG) is considered to be one of the most common surgical procedures. This procedure has been the main topic in many clinical research studies, which have assessed the effect of the procedure on patients' outcomes. Like other surgical procedures, this procedure is also accompanied by a number of unwanted complications, including those of the respiratory system. Since the respiratory system plays an integral role in defining the clinical outcome of patients, improvements in studies that can assess and predict clinical outcomes of the respiratory system, assume greater importance. There are a number of predictive models which can assess patients in the preoperative period and introduce a number of risk factors, which could be considered as prognostic factors for patients undergoing CABG. The respiratory system is among the clinical systems that are assessed in many prediction scoring systems. This review assesses the main studies which have evaluated the possible risk factors for postoperative respiratory mortality and morbidity, in patients undergoing CABG. PMID- 24223340 TI - A Clinical Evaluation of the GemStar(r) and the AmbIT(r) Pumps for Patient Controlled Epidural Analgesia. AB - BACKGROUND: Patient-controlled analgesia is used for both labor and postoperative analgesia. OBJECTIVES: This study aimed to assess user satisfaction and functionality of two ambulatory, electronic patient controlled analgesia devices, the GemStar pump Hospira Inc., Illinois, USA) and the ambIT Ambulatory Infusion Therapy pump (Sorenson Medical Products, Utah, USA). PATIENTS AND METHODS: It was a randomized clinical trial of laboring women and postoperative gynecology patients receiving patient-controlled epidural analgesia. Patients were randomized to use one of the pumps and both anesthesiologists and patients completed questionnaires about aspects of pump function, and rated their satisfaction with the equipment. Midwives and high-dependency unit nurses also evaluated the pumps in each clinical setting. RESULTS: Forty patients, 20 laboring women and 20 postoperative patients were randomized and completed the study. The pumps were compared by nine anesthesiologists. Patient and staff satisfaction with both devices was high. Patient satisfaction did not significantly differ between groups (median 10 [8, 10] for the GemStar and 10 [9, 10] for the ambIT, P = 0.525]. The median staff satisfaction score was 8 [6, 8] for the GemStar and 7 [5, 8] for the ambIT (P = 0.154). Both patient cohorts rated each pump highly for most aspects of clinical function. Staff rated the ambIT pump more favourably with respect to portability and storage at the bedside whilst the GemStar had better assessments with respect to its consumables and interactions involving the electronic interface. CONCLUSIONS: Both devices were well-rated by patients and staff, with no significant difference between them for overall satisfaction, and only minor differences with respect to their respective strengths and weaknesses. PMID- 24223341 TI - Effects of single-dose pregabalin on postoperative pain in dacryocystorhinostomy surgery. AB - BACKGROUND: Postoperative pain of dacryocystorhinostomy (DCA) surgery is one of the serious issues to be considered. Administrating opioids to relieve postoperative pain and facing their increasing side effects in eye surgeries, make the use of non-opioid drugs inevitable. OBJECTIVES: The present study examined the efficacy of pregabalin in alleviating the postoperative pain of DCA surgery. PATIENTS AND METHODS: The present study has been carried out as a double blind, randomized clinical trial on the patient candidates for DCR. The patients were randomly divided in to two groups of pregabalin and placebo. Patients in pregabalin group received 300 mg of pregabalin, an hour before the operation in the morning of the surgery. Pain intensity on visual analog scale (VAS) was recorded until 24 hours after the operation; also the rate of administrated opioids and nausea/vomiting frequency were recorded during the first 24-hour period after the operation and the resultsof the two groups were compared. RESULTS: Postoperative pain intensity in the pregabalin group at the time of recovery was significantly lower than that of the placebo group (P = 0.001) until 24 hours after the surgery. In the pregabalin group 17.5% of the patients received opioids while in the placebo group the figure was 52.5% (P = 0.001). Nausea frequency was also higher in the placebo group than the pregabalin group (P = 0.003). CONCLUSIONS: A single 300 mg dose of pregabalin, an hour before DCA can effectively reduce pain intensity and also reduce opioid dose and nausea/vomiting. PMID- 24223342 TI - Postoperative gabapentin to prevent postoperative pain: a randomized clinical trial. AB - BACKGROUND: Gabapentin is an anticonvulsant that has postoperative analgesic effects but there are limited studies on its postoperative administration. OBJECTIVES: The present study was conducted to evaluate the effect of the postoperative oral gabapentin on pain and morphine consumption. PATIENTS AND METHODS: In a double blind, randomized study, 64 patients undergoing internal fixation of tibia under spinal anesthesia were randomly assigned to receive oral gabapentin or placebo immediately after the surgery. Pain scores were recorded at time points of 2, 12 and 24 hours postoperatively using visual analog scale (VAS). Time duration from the end of surgery until morphine administration and total morphine requirement in the first 24 hours were recorded. RESULTS: The estimated duration of surgeries was 120-150 minutes. VAS score was not significantly different between the two groups at 2, 12 and 24 hours after surgery. There was no significant morphine consumption difference between the groups. CONCLUSIONS: Our study showed no significant analgesic efficacy of oral gabapentin 300 mg immediately after tibia internal fixation surgery under spinal anesthesia at time points of 2, 12 and 24 hours postoperatively. PMID- 24223343 TI - Granisetron versus dexamethasone in prophylaxis of nausea and vomiting after laparoscopic cholecystectomy. AB - BACKGROUND: Post-operative nausea and vomiting (PONV) is one of the common problems after laparoscopic cholecystectomy. OBJECTIVES: The current study aimed to compare Dexamethasone effect with that of Granisetron in prevention of PONV. PATIENTS AND METHODS: In the current study 104 patients aged 20-60 with ASA class I or II who were candidates for laparoscopic cholecystectomy were included in the study. Patients were randomly divided into two groups of A and B. 15 minutes before anesthesia induction, in group a patient's 3 mg Granisetron and in group B patients 8 mg Dexamethasone was intravenously injected. Then both groups underwent general anesthesia with similar medications. After operation the prevalence of nausea and vomiting was assessed at three time intervals (0-6 hours, 6-12 hours and 12-24 hours after consciousness). SPSS software version 16 was employed to analyze data. T test, chi-square test and Fischer exact test were performed level of significance was P < 0.05. RESULTS: There was no significant difference between age, gender proportion, weight, height, and body mass index (BMI) of patients in the two groups. In Dexamethasone group, seven patients experienced nausea and three patients had vomiting, and in Granisetron group, five patients experienced nausea and three patients had vomiting after consciousness. Statistical analysis indicated no significant difference between the two groups in this regard. CONCLUSIONS: Intravenous injection of 8 mg Dexamethasone or 3 mg Granisetron before anesthesia induction had similar effects in prophylaxis of nausea and vomiting after laparoscopic cholecystectomy. PMID- 24223344 TI - Evaluation of a low dose ketamine in post tonsillectomy pain relief: a randomized trial comparing intravenous and subcutaneous ketamine in pediatrics. AB - BACKGROUND: Pain control in children is still a therapeutic dilemma. Preschool patients are affected from undesirable effects of postoperative pain more than adults. Tonsillectomy is associated with a high incidence of postoperative pain, not only complicating the recovery, but also delaying patients discharge. OBJECTIVES: Despite employing different surgical and anesthetic strategies in post-tonsillectomy pain relief, this is still a clinical problem. The study was designed to evaluate the efficacy of a low dose ketamine in post tonsillectomy pain relief. PATIENTS AND METHODS: Our prospective randomized double blinded study enrolled 75 pediatric patients (3-10 years old) who were scheduled for a tonsillectomy procedure. Patients were randomly assigned to one of three groups receiving; intravenous (IV) ketamine 0.5mg/kg, subcutaneous (SC) ketamine 0.5 mg/kg and placebo at the end of the operation. Post-operative pain score was assessed using modified CHEOPS. RESULTS: In our study we did not find any significant difference among the three groups regarding sex, age, and weight, duration of operation, hemodynamic stability, and nausea and vomiting. However, in ketamine groups, pain score and analgesic consumption were significantly lower (P < 0.00). The efficacy of the both ketamine groups was similar. CONCLUSIONS: The study demonstrated that the both subcutaneous and intravenous injections of ketamine, at the end of the operation, were safe and effective for post tonsillectomy pain control. Ketamine reduced postoperative analgesic medications consumption without increasing the risk of complications. PMID- 24223345 TI - Comparison of remifentanil and fentanyl regarding hemodynamic changes due to endotracheal intubation in preeclamptic parturient candidate for cesarean delivery. AB - BACKGROUND: Intravenous opioids are administered to prevent and control hemodynamic changes due to endotracheal intubation. Except for special cases such as preeclampsia, these drugs are not recommended for parturants candidate for cesarean section because of the respiratory depression caused in the newborn. OBJECTIVES: According to rapid metabolism of remifentanil, the current study aimed to compare hemodynamic changes in preeclamptic parturants who received remifentanil and fentanyl for cesarean section under general anesthesia. PATIENTS AND METHODS: This single blind randomized clinical trial was performed on preeclamptic pregnant women candidate for cesarean section under general anesthesia. They were divided into two groups. In the first group 0.05 MUg/kg/min remifentanil was infused for 3 minutes before induction of anesthesia and in the second group 1ml (50 MUg) fentanyl was injected before induction. Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after intubation and also Apgar index were measured and compared between the two groups. RESULTS: All hemodynamic variables increased after intubation in the fentanyl group (pSBP = 0.146, pDBP = 0.019, pHR < 0.001). Additionally, decrease in SBP (P = 0.018) and DBP (P = 0.955) and mild increase in HR (P = 0.069) after intubation in the remifentanil group was observed. No significant difference was found between Apgar indexes of the two groups (P = 0.771). CONCLUSIONS: It can be postulated that remifentanil can be used in partituents candidate for cesarean delivery under general anesthesia to prevent severe increase in blood pressure and heart rate during tracheal intubation without adverse effects on newborn. PMID- 24223346 TI - Propofol alleviates intractable migraine headache: a case report. AB - ABSTRACT: Several medications have been proposed as the first line drugs in the treatment of migraine attack. However, the low efficacy, potential complications of medications and the intolerance of some patients for oral route due to nausea and vomiting establish a difficult situation in some migraine patients. This report describes a dramatic pain relief with 60 mg of intravenous propofol in a patient with migraine attack refractory to treatment with metoclopramide, promethazine, dexamethasone and meperidine. Pain relief in this patient besides earlier case reports suggests that subanesthetic doses of propofol may be an alternative to other treatment modalities for acute migraine. PMID- 24223347 TI - Cervical decompression and unexpected soft tissue oedema: case report. AB - ABSTRACT: Acute upper airway obstruction (UAO) is a life threatening complication that is well recognized after carotid endarterectomy, thyroidectomy and pharyngeal area intervention. It is not widely acknowledged that airway obstruction can occur after cervical spinal fusion surgery which was first described in 1955. There are a number of common postoperative problems which may become apparent in the short to medium term. These include: sore throat, dysphagia, hoarseness, dysphonia, recurrent laryngeal nerve palsy and soft tissue swelling. PMID- 24223348 TI - Trigeminal neuralgia-divided but not classified. PMID- 24223349 TI - Evolution and mode of action of pulsed radiofrequency. PMID- 24223350 TI - Comparison between the Effects of Rocuronium, Vecuronium, and Cisatracurium Using Train-of-Four and Clinical Tests in Elderly Patients. AB - BACKGROUND: Postoperative residual blockade, longer duration of action for neuromuscular blockade, and slower recovery were relatively common in elderly patients. OBJECTIVES: We aimed to investigate the safety of train-of-four ratio and clinical tests in the assessment of patient recovery, and to determine the effects of the rocuronium, vecuronium, and cisatracurium on intubation, extubation and recovery times in elderly patients undergoing abdominal surgery. PATIENTS AND METHODS: After obtaining institutional approval and informed consent, 60 patients over 60 years old and undergoing elective abdominal operations were included in this double-blind, randomized clinical trial. Following a standard anesthesia induction, 0.6mg kg-1 rocuronium, 0.1mg kg-1 vecuronium, and 0.1mg kg-1 cisatracurium were administered to the patients in Group R, Group V, and Group C, respectively. Train-of-four (TOF) ratios were recorded at 10-minute intervals during and after the operation. Modified Aldrete Score (MAS) and clinical tests were recorded in the recovery room at 10-minute intervals. In addition, intubation and extubation times, duration of recovery room stay, and any complications were recorded. RESULTS: Intubation time was found to be shorter in Group R than that in Groups V and C (P ? 0.001). Times to positive visual disturbances and grip strength tests were shorter in Group C than that in Group V (P = 0.016 and P = 0.011, respectively). In Group R and group C, time to TOF >= 0.9 was significantly longer than all positive clinical test times except grip strength (P < 0.05). CONCLUSIONS: We hold the opinion that cisatracurium is safer in elderly patients compared to other drugs. We also concluded that the usage of TOF ratio together with clinical tests is suitable for assessment of neuromuscular recovery in these patients. PMID- 24223351 TI - The Effect of Epidural Bupivacaine on BIS Levels in the Awake Phase and on the Maintenance Doses of Propofol and Fentanyl During General Anesthesia. AB - BACKGROUND: Simultaneous administration of epidural local anesthetic agents (LA) and general anesthetics (intravenous or inhaled) is a common procedure in patients undergoing major operations. The effects of epidural anesthesia during combined general-epidural anesthesia on the alertness level (CGEA) in the awake phase and the doses of anesthetics have been reported. OBJECTIVES: The present study was designed to determine the effects of epidural bupivacaine on the alertness level measured by bispectral index (BIS) in the awake phase and the maintenance doses of propofol and fentanyl during general anesthesia for vascular operation on the lower limb. PATIENTS AND METHODS: A double-blinded randomized clinical trial was conducted on patients awaiting vascular surgery on lower extremities in a teaching hospital from October 2007 to October 2008. During the epidural anesthesia, the control group received 0.9% NS while 0.125% bupivacaine was injected in the case group via the epidural route. No sedative drug was utilized for epidural catheter placement. The BIS measurement was performed in both groups during the awake phase, before performing epidural anesthesia, and 10 minutes after epidural injection at 1-min intervals for 15 min. After induction of general anesthesia in both groups, anesthesia maintenance was established using the infusion of propofol with the aim of keeping the BIS level between 40 and 50 throughout the anesthesia. At the end of the study period, maintenance dose requirements of propofol and fentanyl were measured. RESULTS: Thirty-two patients were enrolled in the study. There was no difference in BIS levels of the two groups in the awake phase. There was a significant difference between the propofol and fentanyl requirements of the two groups. CONCLUSIONS: Performing CGEA using bupivacaine was reported to reduce propofol and fentanyl doses required to maintain BIS levels between 40 and 50 considerably. PMID- 24223352 TI - The effect of needle type, duration of surgery and position of the patient on the risk of transient neurologic symptoms. AB - BACKGROUND: The incidence of transient neurologic symptoms (TNS) after spinal anesthesia with lidocaine is reported as high as 40%. OBJECTIVES: This prospective clinical trial was designed to determine the incidence of TNS in patients who underwent spinal anesthesia with two different needles, in two different surgical positions. PATIENTS AND METHODS: The present randomized clinical trial was conducted on 250 patients (ASA I-II), who were candidates for surgery in supine or lithotomy positions. According to the needle type (Sprotte or Quincke) and local anesthetics (lidocaine and bupivacaine) all patients were randomly divided into four groups. After performing spinal anesthesia in sitting position, the position was changed into supine or lithotomy, according to surgical procedure. The patients were observed for complications of spinal anesthesia during the first five post-operative days. The primary end-point for this trial was to recognize the incidence of TNS among the four groups. Our secondary objective was to evaluate the effect of patient's position, needle type, and duration of surgery on the development of TNS following spinal anesthesia. RESULTS: TNS was most commonly observed when lidocaine was used as anesthetic drug (P = 0.003). The impact of needle type, was not significant (P = 0.7). According to multivariate analysis, the duration of surgery was significantly lower in cases suffering from TNS (P = 0.04). Also, the risk of TNS increased following surgeries performed in lithotomy position (P = 0.00). CONCLUSIONS: According to the results of this clinical study, spinal anesthesia with lidocaine, and the lithotomy position in surgery increased the risk of TNS. PMID- 24223353 TI - Effectiveness of lumbar drain versus hyperventilation to facilitate transsphenoidal pituitary (suprasellar) adenoma resection. AB - BACKGROUND: Developing controlled hypercarbia is a known scheme of lowering the suprasellar part of the adenoma in order to assist the surgeon, which acts through raising the ICP and therefore the CSF pressure. OBJECTIVES: The purpose of this study is to compare the effect of introducing a lumbar drain with that of controlled hypercapnia on the quality of transsphenoidal pituitary tumor resection and CSF leak. PATIENTS AND METHODS: Fifty two patients with pituitary adenoma who underwent transsphenoidal hypophysectomy by the same surgeon were included. They were randomly divided into two groups. A lumbar drain catheter introduced into the L3-L4 subarachnoid space under local anesthesia in all patients. The same anesthesia was performed in both groups. In the study group, we used a saline injection into the subarachnoid space versus hypoventilation in the control group in order to increase the ICP according to the surgeon's request. The surgeon's satisfaction during the tumor resection and the resection time were assessed during the surgery. The CSF catheter was closed and sent with the patient for CSF drainage. If there was no CSF leak, the catheter removed 24 hours later. With evidence of a CSF leak, we used the catheter as a lumbar drain. The time taken for the leakage control was assessed. RESULTS: The satisfaction came from 21 (87.5%) and 2 (9.1%) for surgeon in the first and the second group respectively (P = 0.0001). CSF leakage time in the first and the second group was 1.6 +/- 0.24 and 5 +/- 0.50 respectively. It revealed a significant difference between the two groups (P = 0.001). The mean resection time was 13.54 +/- 0.66 minutes in the study group; and 30.91 +/- 0.98 minutes in the control group. CONCLUSIONS: In summary, the method described here for ICP manipulation is an effective procedure for a better visualization of the pituitary tumor during transphenoidal resection by surgeon and beneficial in managing the CSF leak following surgery. PMID- 24223354 TI - Evaluation of education, attitude, and practice of the Turkish anesthesiologists in regional block techniques. AB - BACKGROUND: The demand for regional blocks from both patients and surgeons has significantly increased in anesthesia practice during the last 30 years. Although the studies show that the complications are rare, regional blocks still have serious difficulties which can be prevented by training programs. OBJECTIVES: The purpose of this study was to determine the factors affecting the educational methods, attitude and practice of the Turkish anesthesiologists in regional blocks during and following residency programs. PATIENTS AND METHODS: Anesthesiologists were asked to answer a questionnaire. Educational proficiency was determined by at least 50 spinal, 50 epidural and 50 peripheral block applications during residency. Specialists were asked for the numbers of spinal, epidural and peripheral blocks (PBs) they applied in 2009. The mean and median values were calculated. RESULTS: One hundred and eighty-eight anesthesiologists (84.3 %) agreed to participate in the study. While all participants had made their first attempts in neuraxial blocks (NBs) when they were residents, this ratio was detected as 96.8% for PBs. All participants learned neuraxial and PBs on patients in the operating theater. Education proficiency ratios for spinal, epidural and PBs were 98.1 %, 92.5 % and 62.3 %, respectively. Age, perception of adequate training, nerve block rotation, adequate application in education, following innovations were the factors which significantly affected the number of PBs in practice according to univariate analysis. The participants who consider their applications on NBs were adequate (P = 0.029) and the ones working in state or private hospitals (P = 0.017), applied NBs significantly above the median number. CONCLUSIONS: Anesthesiologists had adequate education and practice of NB applications but a significant proportion of participants (51.8%) lacked both in PBs applications. We believe that NBs are more easily learned than PBs during residency training program. PMID- 24223355 TI - Propofol is Effective to Depress Fentanyl-Induced Cough during Induction of Anesthesia. AB - BACKGROUND: Various attempts have been made to reduce the incidence of fentanyl induced cough during anesthesia induction. We hypothesized that an appropriate dose of propofol might suppress fentanyl-induced cough. OBJECTIVES: A study had been designed to observe the effects of propofol on a fentanyl-induced cough during anesthesia induction. PATIENTS AND METHODS: We performed a randomized, double-blind study to evaluate the effect of the pre-emptive use of minimal dose intravenous propofol (20 mg) on the incidence of cough caused by a larger bolus of intravenous fentanyl. Group 1 patients were given fentanyl at a dosage of 4 ug/kg. Group 2 received 4ug/kg fentanyl and 20 mg propofol. The two groups were evaluated in 0, 5 and 10 second intervals following the injection of fentanyl. RESULTS: Mean age, weight, and, height was 35 +/- 10.45, 67.99 +/- 10.92, and 165.33 +/- 31.84 respectively. The incidence of fentanyl induced cough was 29 (74.4%) in placebo group compared with 10 (25.6%) in the propofol group. There was a significant difference in the incidence and severity of cough between group 1 and 2 (P < 0.0001). This study also showed that propofol could decrease cough incidence in patients who smoke. CONCLUSIONS: Priming dose of propofol (20mg) one minute prior to fentanyl injection was effective in suppressing a fentanyl induced cough. PMID- 24223356 TI - Is presence of bacteria in preoperative microscopic urinalysis of the patients scheduled for cardiac surgery a reason for cancellation of elective operation? AB - BACKGROUND: In some hospitals, urinalysis is done routinely for all patients scheduled for cardiac surgery. Occasionally pyuria or bacteria is reported in the microscopic urinalysis of these patients that are clinically asymptomatic for urinary tract infections. OBJECTIVES: WE WERE SEEKING ANSWER TO THIS QUESTION: is the presence of a different number of bacteria in preoperative microscopic urinalysis of asymptomatic patients scheduled for cardiac surgery indicative of potential postoperative complications and as a result, a good reason to postpone the operation? PATIENTS AND METHODS: We conducted a retrospective cross-sectional study based on the review of the medical records of 1165 patients who underwent open-heart surgery. RESULTS: One hundered and fifty one patients were eligible in our established criteria. There were no significant difference between their demographic characteristics and the same number of randomly selected patients with normal urinalysis who had underwent open-heart surgery. In the bacteriuria group, two patients, and in the control group, three patients had an infection at the operation sites in the post-operative period, which was not a significant finding between two groups (P = 0.503). CONCLUSIONS: We recommend that in the absence of symptoms of urinary tract infection, urinalysis is not necessary and not cost beneficial in the preoperative evaluation of patients scheduled for open heart surgery. PMID- 24223357 TI - Does changes in the electrical resistance of an acupuncture meridian predict pain intensity following orthopedic surgery? AB - BACKGROUND: Several methods for assessment of severity of pain have been proposed but all of them are subjective. OBJECTIVES: This study evaluated the association concerning changes in electrical resistance (ER) between two acupuncture points and severity of postoperative pain in order to define an objective measurement of pain. PATIENTS AND METHODS: In a cross-sectional study, 50 patients undergoing lower extremity orthopedic surgery with postoperative moderate to severe pain (VAS > 4,) were consecutively enrolled. In the recovery room, the patients' pain scores were assessed and in patients with VAS > 4, the electrical resistance between Li4 and Li11 acupuncture points as well as pain scores was measured prior and following analgesic administration. RESULTS: Following meperidine use, the mean VAS significantly decreased and the ER between the two acupoints was significantly increased. However, Pearson correlation analysis did not reveal any association between the trends of pain intensity and ER (P > 0.05). The ER change in patients operated under epidural anesthesia was significantly less than those who experienced general or spinal anesthesia. CONCLUSIONS: There is a coincidence of pain relief and change in the ER of acupuncture meridians without significant association. The diagnostic value of ER for pain, stress response or any other physiologic outcome needs to be investigated in clinical trials with a well defined control group, with more accurate instruments and probably in different acupuncture meridians. PMID- 24223358 TI - Sudden Death in a Patient with Carney's Complex. AB - Carney's complex is a rare autosomal dominantly inherited multiple endocrine neoplasia syndrome that involves spotty skin pigmentations, recurrent cardiac myxomas, endocrine hyperactivity, pituitary adenomas, peripheral nerve tumors, testicular tumors, and ovarian lesions. We present a case of sudden cardiac death in a 40 year old female with a history of Carney's complex with recurrent cardiac myxomas presenting for exploratory laparotomy and enblock adnexal resection of a slowly enlarging right sided ovarian mass. This case highlights the risk for sudden death in these patients as well as the preoperative assessment that should be undertaken by the anesthesiologist as it relates to Carney's complex. PMID- 24223359 TI - Introducing Plagiarism and Its Aspects to Medical Researchers is Essential. PMID- 24223360 TI - Pain management in intensive care unit patients: the role of ultra-short acting opioid: remifentanil. PMID- 24223361 TI - Desflurane versus opioid anesthesia for cardiac shunt procedures in infants with cyantoic congential heart disease. AB - BACKGROUND: Placement of a Blalock-Taussig (BT) shunt is frequently performed for palliation of cyanotic congenital heart disease (CCHD). OBJECTIVES: Inhalational anesthetics, when used in adult heart surgery, offer advantages of myocardial protection and decrease in use of inotropes, duration of ventilation, ICU and hospital length of stay (LOS).There is little literature, however, in the comparative use of inhalational and narcotic anesthesia in CCHD. PATIENTS AND METHODS: Following Institutional Ethical Review Board approval and parental consent, 35 patients presenting for BT shunt were prospectively randomized to receive either a desflurane anesthetic or a narcotic anesthetic. Institutional practice for all patients undergoing BT shunt is to undergo cardiopulmonary bypass (CPB) following median sternotomy. Induction was accomplished with 5-7% sevoflurane in 100% oxygen, 2ug/kg fentanyl, 0.05mg/kg midazolam and 0.1mg/kg vecuronium. After intubation, patients in the narcotic group (n=16) received an additional 5-10ug/kg fentanyl, 0.1mg/kg midazolam, 100% oxygen and vecuronium. Patients in the inhalational group (n=19) received desflurane, 0.6-1 MAC, 100% oxygen, 0.05mg/kg midazolam, IV paracetamol 15mg/kg and vecuronium. At the end of surgery, patients were transferred to the ICU and received IV paracetamol and midazolam. Ventilation was weaned when the patient was hemodynamically stable. Demographics, baseline, intra and post-op heart rates, duration of inotrope use, ICU and hospital LOS, pre and post-op creatinine and serious adverse events (SAE) were recorded. Data were analyzed using Student, paired t, Mann-Whitney U and Chi square/Fisher exact tests, P < 0.05 significant. RESULTS: Demographic data were similar, except for a modestly higher pre-op heart rate in the group receiving opioid anesthesia. Patients receiving desflurane had a significantly shorter duration of mechanical ventilation and length of ICU and hospital stay. Inotrope use was similar in both groups. The group receiving opioid anesthesia had an increase in creatinine post operatively which was not observed in the desflurane group. There was no difference in incidence of significant adverse events in either group. CONCLUSIONS: Use of inhalational anesthesia has increased in adult cardiac surgery and has proved to reduce duration of elective ventilation, decrease ICU and hospital LOS, and mortality. Inhalational anesthetics are less well-studied in CCHD. In the current study, desflurane was chosen because of its low solubility, decreased recovery time and lack of metabolism or organ system toxicities. Although it is a popular belief that desflurane is associated with tachycardia and airway irritation, findings of the current study are consistent with those of the previous works demonstrating a lack of these side effects below 1 MAC3. No hemodynamic instability was encountered and there was no evidence that desflurane exerted a negative inotropic effect. Markers of cardio protection were not examined, although desflurane may have had a renal protective effect compared to narcotic technique. In the current study, a desflurane anesthetic for BT shunt decreased the duration of mechanical ventilation and ICU and hospital LOS by nearly three days, with no difference in perioperative morbidity or mortality. Larger studies are required to determine whether these changes result in overall decreased complication rate and morbidity/mortality and whether desflurane has a cardio or renal protective effect in the patient population. PMID- 24223362 TI - Post tonsillectomy pain: can honey reduce the analgesic requirements? AB - BACKGROUND: Tonsillectomy with or without adenoidectomy is one of the most common surgical procedures performed worldwide, especially for children. Oral honey administration following tonsillectomy in pediatric cases may reduce the need for analgesics via relieving postoperative pain. OBJECTIVES: The aim of this study was to evaluate the effects of honey on the incidence and severity of postoperative pain in patients undergoing tonsillectomy. PATIENTS AND METHODS: A randomized, double blind, placebo controlled study was performed. One hundred and four patients, who were older than eight, and were scheduled for tonsillectomy, were divided into two equal groups, honey and placebo. Standardized general anesthesia, and postoperative usual analgesic, and antibiotic regimen were administrated for all patients. Acetaminophen plus honey for the honey group, and acetaminophen plus placebo for the placebo group were given daily. They began to receive honey or placebo when the patients established oral intake. RESULTS: The difference between acetaminophen and acetaminophen plus honey groups was statistically significant both for visual analogue scale (VAS), and number of painkillers taken within the first three postoperative days. The consumption of painkillers differed significantly in every five postoperative days. No significant difference was found between groups regarding the number of awaking at night. CONCLUSIONS: Postoperative honey administration reduces postoperative pain and analgesic requirements in patients after tonsillectomy. As the side effects of honey appear to be negligible, consideration of its routine usage seems to be beneficial along with routine analgesics. PMID- 24223363 TI - The Effect of Inhalation of Aromatherapy Blend containing Lavender Essential Oil on Cesarean Postoperative Pain. AB - BACKGROUND: Pain is a major problem in patients after cesarean and medication such as aromatherapy which is a complementary therapy, in which the essences of the plants oils are used to reduce such undesirable conditions. OBJECTIVES: In this study, the effect of aromatherapy using Lavender (Lavandula) essential oil on cesarean postoperative pain was assessed. MATERIALS AND METHODS: In a triple blind, randomized placebo-controlled trial study, 60 pregnant women who were admitted to a general hospital for cesarean section, were divided randomly into two groups. After cesarean, the Lavender group inhaled about 3 drops of 10% Lavender oil essence and the placebo group inhaled 3 drops of placebo after the start of postoperative pain, four, eight and 12 hours later, for 5 minutes from the 10 cm distance. Patient's pain was measured by the VAS (Visual Analog Scale) score before and after each intervention, and vital sign, complications and level of satisfaction of every patient were recorded before and after aromatherapy. RESULTS: There was no statistically significant difference between groups in age, height, weight, and time to the first analgesic requirement. Patients in the Lavender group had less postoperative pain in four (P = 0.008), eight (P = 0.024) and 12 (P = 0.011) hours after first medication than the placebo group. The decreased heart rate and patients' level of satisfaction with analgesia were significantly higher in the Lavender group (P = 0.001). In the placebo group, the use of diclofenac suppositories for complete analgesia was also significantly higher than the Lavender group (P = 0.008). CONCLUSIONS: The inhaled Lavender essence may be used as a part of the multidisciplinary treatment of pain after cesarean section, but it is not recommended as the sole pain management. PMID- 24223364 TI - Conscious Sedation and Analgesia in Colonoscopy: Ketamine/Propofol Combination has Superior Patient Satisfaction Versus Fentanyl/Propofol. AB - BACKGROUND: Colonoscopy is performed without preparing sedation in many countries. However, according to the current literature patients are more satisfied when appropriate sedation is prepared for them. OBJECTIVES: We hypothesize that propofol-ketamine may prepare more patient satisfaction compared to propofol-fentanyl combination. PATIENTS AND METHODS: Sixty adult patients older than 18 with ASA physical status of I, II or III were enrolled in the present study after providing the informed consent. They were prospectively randomized into two equal groups: 1- Group PF: was scheduled to receive IV bolus dose of fentanyl 1ug/kg and propofol 0.5mg/kg. 2- Group PK: was scheduled to receive IV bolus dose of ketamine 0.5mg/kg and propofol 0.5mg/kg. As a primary goal, patient's satisfaction was assessed by the use a Likert five-item scoring system in the recovery. Comparisons of hemodynamic parameters (mean heart rate, mean systolic blood pressure, mean diastolic blood pressure), mean Spo2 values during the procedure and side effects such as nausea, vomiting, and psychological reactions during the recovery period were our secondary goals. Level of sedation during the colonoscopy was assessed with the Observer's Assessment of Alertness/Sedation score (OAA/S). RESULTS: Mean satisfaction scores in the group PK were significantly higher than the group PF (P = 0.005) while the level of sedation during the procedure was similar (P = 0.17). Hemodynamic parameters and SpO2 values were not significantly different (P > 0.05). Incidence of nausea and vomiting was the same in both groups. CONCLUSIONS: IV bolus injection of propofol ketamine can lead to more patients' satisfaction than the other protocols during colonoscopy. PMID- 24223365 TI - Intravenous paracetamol for postoperative analgesia in laparoscopic cholecystectomy. AB - BACKGROUND: Although opioids are the main choice for acute postoperative pain control, many side effects have been reported for them. NSAIDs and paracetamol have been used extensively as alternatives, and it seems that they are more effective for minor to moderate pain control postoperatively when have been used alone or in combination with opioids. As laparoscopic cholecystectomy poses moderate pain postoperatively, this study was planned to assess whether paracetamol is able to provide effective analgesia as a sole analgesic at least in the first few hours post operatively. OBJECTIVES: We evaluated the effect of intravenous Paracetamol on postoperative pain in patients undergoing laparoscopic cholecystectomy. PATIENTS AND METHODS: This is a randomized double- blind clinical trial study. 30 patients ASA class I, aged 18 to 50 years, candidate for laparoscopic cholecystectomy were recruited, and randomly divided into two equal groups. Group A (paracetamol group) received 1 gr paracetamol and group B received placebo ten minutes after the induction of anesthesia. 0.1 mg/Kg Morphine was administered intravenously based on patients compliant and pain score >3. Pain score and the opioids consumption were recorded in the first six hours postoperative. Patient's pain was measured by the VAS (Visual Analog Scale). RESULTS: The pain score was lower in group A (P= 0.01), but the morphine consumption showed no significant difference between the groups (P= 0.24) during the first 6 hours postoperatively. CONCLUSIONS: Although paracetamol (1gr) has caused a better pain relief quality but it is not a suitable analgesic for moderate pain control in acute phase after surgery alone. PMID- 24223366 TI - Intravenous application of pulsed radiofrequency-4 case reports. AB - It has been suggested that PRF might possibly have an effect on the immune cells. We considered using the intravenous route to apply PRF in conditions that are caused by an unresolved immune action or connected to allostatic load, implicating an abnormally reacting immune system to obtain a systemic effect that could possibly be an additional tool in treating some of these conditions. These manuscript reports four cases that illustrate the wide variety of conditions where this new technique might be helpful. PMID- 24223367 TI - Central nervous system toxicity after botulinum neurotoxin injection. AB - Since Its first description of botulism toxicity in 1820s, specific formulations of botulinum neurotoxin (BoNT) have been introduced with different clinical benefits. However, there is increasing number of adverse events reported to Food and Drug Administration. This report presents the case of 62-year-old woman with Parkinson's disease who received BoNT injections to treat painful spasticity in her hands. She developed severe generalized dystonia shortly after BoNT injections. PMID- 24223368 TI - How to define an author? Awareness of authorship criteria. PMID- 24223369 TI - A comparison of peroxisome proliferator-activated receptor-alpha agonist and antagonist on human umbilical vein endothelial cells angiogenesis. AB - BACKGROUND: There are controversial reports about the antiangiogenic effects of peroxisome proliferator-activated receptor alpha (PPARalpha). In the current study, we compared the effects of PPARalpha agonist and antagonist on human umbilical vein endothelial cells (HUVECs) angiogenesis with matrigel assay. MATERIALS AND METHODS: HUVECs (1 * 10(5) cells/well) treated with PPARalpha agonist (fenofibrate) and antagonist (GW6471) were cultured on matrigel for 24 h. Treated cells were stained with calcein and investigated by fluorescent microscopy. The obtained images were also analyzed by AngioQuant software. Finally, the data were analyzed using SPSS 15 software, Kruskal-Wallis and one way ANOVA. RESULTS: Statistical analysis showed that fenofibrate significantly inhibit the tube formation (size, length, junction) (P < 0.05) but there was a trend to increased angiogenesis in GW6471 treated group (P > 0.05). CONCLUSION: These results showed that PPARalpha agonist is effective in suppression of angiogenesis. Further studies are needed to confirm these results in in vivo studies. PMID- 24223370 TI - Lithium carbonate inducing disorders in three parameters of rat sperm. AB - BACKGROUND: Lithium has a significant impact in reducing the symptoms of bipolar mania but in long periods of use with therapeutic doses can cause several disorders in various organs including the reproductive system. In this study, the effect of lithium on the sperm concentration and motility and forms of abnormal cells has been examined. MATERIALS AND METHODS: Male Wistar rats under the 48-day treatment with lithium carbonate at doses of 10, 20, and 30 mg/kg bw/day were kept in standard conditions. At the end of this period, sperm cells isolated from the cauda epididymis were counted, motility was estimated, and stained with smear papanicolaou stain. RESULTS: In lithium-treated groups, the rate of spermatogenesis and sperm quality were reduced and was seen in a dose-dependent manner. DISCUSSION: Lithium alters intracellular signaling pathways such as inositol phosphate metabolic cycle and cyclic adenosine mono phosphate (cAMP) system and adenosine triphosphate (ATP) synthesis. It also interferes in the division of sex cells to produce mature sperm and showed changes in the sperm cell membrane, function, and structure. PMID- 24223371 TI - Median nerve somatosensory evoked potentials in medical students: Normative data. AB - BACKGROUND: The median nerve N20 component constitutes the initial response of the primary somatosensory cortex to somatosensory stimulation of the upper extremity. Knowledge of the underlying generators is important for basic understanding of the initial sequence of cortical activation. MATERIALS AND METHODS: In the present study, normative data of cortical evoked potentials in particular of N20 wave onset and peak latencies by median nerve stimulation in a group of 100 medical students aged between 18 and 30 years were documented and the effect of physiological variables were studied. Descriptive statistics and Student t-test were used to analyze the healthy subjects and to compare N20 latencies for handedness, respectively. Regression analysis was used to show association between average N20 latencies and physiological variables from which regression formulae were calculated to predict normative values of these parameters. RESULTS: The results of the study indicated that N20 onset and peak latency values are significantly affected by limb length at 95% confidence level. Height is showing as a significant factor affecting N20 onset latencies but it is probably because of high correlation of height with limb length. Age though on linear regression showed some significant correlation with N20 onset and peak latency, multiple regressions showed that it does not affect N20 onset and peak latencies in the presence of other variables. Handedness did not affect both N20 onset and peak latency values. CONCLUSION: Physiological variables do affect the N20 latencies and these should be standardized before usage for research in basic sciences at all age groups. PMID- 24223372 TI - Comparison of the effect of honey and miconazole against Candida albicans in vitro. AB - BACKGROUND: One of the most common causes of vaginitis is candidiasis. The aim of this study is to compare the effect of honey and miconazole against Candida albicans, in vitro. MATERIALS AND METHODS: The different W/V concentrations of honey were prepared at 20, 40, 60, 80, and 95% and different dilutions of miconazole were prepared in 0.05, 5, and 50 MUg/ml. A microdilution of 100/000 cells per ml of a two-day old culture of Candida albicans was prepared in normal saline, after culturing the strain of PTCC 5027 in RPMI 1640 medium. Ten microliters of this dilution was added to 1 ml of the RPMI 1640 medium containing different concentrations of honey and to 1 ml of the RPMI 1640 medium containing different dilutions of miconazole. The cultures were incubated at 35 degrees C for 12, 24, and 48 hours. RESULTS: The growth rate of Candida albicans was determined in the cultures. The results indicated that the honey prevented the growth of C. albicans greatly only at an 80% concentration, whereas, miconazole inhibited it completely. CONCLUSIONS: As Candida albicans is a normal vaginal flora, the inhibitory effect of honey without the fungicide effect is a very good trend in the treatment of vaginal candidiasis. PMID- 24223373 TI - Comparison of Alopecia severity and blood level of testosterone in men suffering schizophrenia with control group. AB - BACKGROUND: Testosterone causes Alopecia that is related to functional testosterone and end organ sensitivity to testosterone. Studies conducted on the relationship of schizophrenia and testosterone have reported different findings. This study was designed to measure the extent of Alopecia in schizophrenic patients which is one of the most important signs of sensitivity to Androgens. MATERIALS AND METHODS: In a cross-sectional study, 98 schizophrenic patients and 95 person of normal population encountered to study in two groups considering inclusion criteria and completing a consent form, in the psychiatric ward of Noor Hospital in Isfahan, Iran. Meanwhile, the record of necessary demographic information a blood sample was taken from every selected person to measure the blood level of testosterone. The severity of Alopecia was measured using Hamilton and Norwood criterion in a blindness condition. Collected data were analyzed using SPSS 19 software and statistical tests of chi(2) and logistic Regression. RESULTS: The mean blood level of testosterone in both studied and control groups were 458.80 +/- 103 and 476.34 +/- 108, respectively, having no significant difference (P > 0.05). There was no significant relationship in both groups between Alopecia severity and the blood level of testosterone. And in comparison of two groups, providing Androgenic Alopecia with a degree higher than three in Hamilton Scale, schizophrenia risk decreases 8.627 times. CONCLUSION: Sensitivity to Androgens and Alopecia probably plays a protective role against schizophrenia, and if Alopecia rate exceeds the rate of grade 2 Hamilton, the risk of schizophrenia decreases 8.62 times. PMID- 24223374 TI - Novel network biomarkers profile based coronary artery disease risk stratification in Asian Indians. AB - BACKGROUND: Multi-marker approaches for risk prediction in coronary artery disease (CAD) have been inconsistent due to biased selection of specific know biomarkers. We have assessed the global proteome of CAD-affected and unaffected subjects, and developed a pathway network model for elucidating the mechanism and risk prediction for CAD. MATERIALS AND METHODS: A total of 252 samples (112 CAD affected without family history and 140 true controls) were analyzed by Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI-TOF MS) by using CM10 cationic chips and bioinformatics tools. RESULTS: Out of 36 significant peaks in SELDI-TOF MS, nine peaks could do better discrimination of CAD subjects and controls (area under the curve (AUC) of 0.963) based on the Support Vector Machine (SVM) feature selection method. Of the nine peaks used in the model for discrimination of CAD-affected and unaffected, the m/z corresponding to 22,859 was identified as stress-related protein HSP27 and was shown to be highly associated with CAD (odds ratio of 3.47). The 36 biomarker peaks were identified and a network profile was constructed showing the functional association between different pathways in CAD. CONCLUSION: Based on our data, proteome profiling with SELDI-TOF MS and SVM feature selection methods can be used for novel network biomarker discovery and risk stratification in CAD. The functional associations of the identified novel biomarkers suggest that they play an important role in the development of disease. PMID- 24223375 TI - A comparison of the effect of pretreatment with intravenous dexamethasone, intravenous ketamine, and their combination, for suppression of remifentanil induced cough: A randomized, double-blind, placebo-controlled clinical trial. AB - BACKGROUND: The injection of remifentanil can cause cough during induction of anesthesia. This study was designed to examine the efficacy of ketamine, dexamethasone, and their combination on remifentanil-induced cough (RIC). MATERIALS AND METHODS: ONE HUNDRED AND TWENTY PATIENTS SCHEDULED FOR ELECTIVE SURGERY WERE RANDOMLY ASSIGNED INTO FOUR GROUPS: Group K received 10 mg ketamine; Group D received 10 mg dexamethasone; Group KD received 10 mg ketamine in combination with dexamethasone; and Group S received saline in a similar volume, five minutes prior to the injection of remifentanil. The incidence and severity of the cough was recorded in each person. RESULTS: The incidence of RIC was significantly lower in Group KD compared to Group K, Group D, and Group S (3.3 vs. 20%, 20%, and 46.7%, respectively, P < 0.05). The severity of RIC was significantly lower in Group KD compared to Group K, Group D, and Group S (P < 0.05). There was no significant difference between Group K and Group D in this regard (P > 0.05). There was no significant difference in the onset time of coughing among the four groups (19.8 +/- 1.3, 20.8 +/- 0.9, 19.0 +/- 1.1, and 19.9 +/- 2.2 in Group K, Group D, Group KD, and Group S, respectively, P > 0.05). CONCLUSION: We found that pretreatment with 10 mg ketamine in combination with 10 mg dexamethasone five minutes prior to the injection of remifentanil could significantly reduce the incidence of RIC, and it was better than using each drug singly. PMID- 24223376 TI - Prevalence of isosporiasis in relation to CD4 cell counts among HIV-infected patients with diarrhea in Odisha, India. AB - BACKGROUND: To determine the prevalence of Isospora belli and its correlation with CD4+ cell counts in HIV-positive patients with diarrhea in this region. MATERIALS AND METHODS: Stool samples from 250 HIV-positive patients, including 200 with diarrhea and 50 without diarrhea included in the study were examined for the presence of enteric parasites under microscopy. Prevalence of the enteric parasites with special reference to I. belli in HIV-positive patients with and without diarrhea were calculated and correlated with their CD4+ cell counts. RESULTS: Enteric parasites were detected in 39% of the HIV patients with diarrhea compared to 30% without diarrhea. I. belli was detected in 22% of the patients with diarrhea and in 4% without diarrhea (P = 0.0019). I. belli was the most common parasite, followed by Entamoeba histolytica/dispar (8%) and Cryptosporidium parvum (5%) in HIV-positive patients with diarrhea. In HIV positive patients without diarrhea, the most common parasite detected was E. histolytica/dispar (12%) followed by C. parvum (6%) and I. belli (4%). The mean CD4 cell count of HIV-positive patients with diarrhea suffering from isosporiasis was 138.35 +/- 70.71. In patients with CD4 cell counts <200/MUl, I. belli was seen in 36/123 stool samples and 2/27 stool samples which was statistically significant (P = 0.0157). CONCLUSION: I. belli was the predominant parasite with a prevalence of 22% among HIV-positive patients with diarrhea, majority having CD4 cell count <200/MUl. This study highlights the importance of routine screening for coccidian parasites in HIV-positive patients with and without diarrhea especially in those with low CD4 cell counts. PMID- 24223377 TI - Design, development and permeation studies of nebivolol hydrochloride from novel matrix type transdermal patches. AB - BACKGROUND: Nebivolol hydrochloride is a third generation beta-blocker with highly selective beta1-receptor antagonist with antihypertensive properties having plasma half life of 10 h and 12% oral bioavailability. The aim of the present investigation was to form matrix type transdermal patches containing Nebivolol hydrochloride to avoid its extensive hepatic first pass metabolism, lesser side effect and increase bioavailability of drug. MATERIALS AND METHODS: Matrix type transdermal patches containing Nebivolol hydrochloride were prepared using EudragitRS100, HPMC K100M (2:8) polymers by solvent evaporation technique. Aluminum foil was used as a backing membrane. Polyethylene glycol (PEG) 400 was used as plasticizer and Dimethyl sulfoxide (DMSO) was used as a penetration enhancer. Drug polymer interactions determined by FTIR and standard calibration curve of Nebivolol hydrochloride were determined by using UV estimation. RESULT: The systems were evaluated physicochemical parameters and drug present in the patches was determined by scanning electron microscopy. All prepared formulations indicated good physical stability. In vitro drug permeation studies of formulations were performed by using Franz diffusion cells using abdomen skin of Wistar albino rat. Result showed best in vitro skin permeation through rat skin as compared to all other formulations prepared with hydrophilic polymer containing permeation enhancer. CONCLUSIONS: IT WAS OBSERVED THAT THE FORMULATION CONTAINING HPMC: EudragitRS100 (8:2) showed ideal higuchi release kinetics. On the basis of in vitro drug release through skin permeation performance, Formulation F1 was found to be better than other formulations and it was selected as the optimized formulation. PMID- 24223378 TI - Awake craniotomy for tumor resection. AB - Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25 year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit. PMID- 24223379 TI - ENT bleeding and leech bite. PMID- 24223380 TI - A review on natural background radiation. AB - The world is naturally radioactive and approximately 82% of human-absorbed radiation doses, which are out of control, arise from natural sources such as cosmic, terrestrial, and exposure from inhalation or intake radiation sources. In recent years, several international studies have been carried out, which have reported different values regarding the effect of background radiation on human health. Gamma radiation emitted from natural sources (background radiation) is largely due to primordial radionuclides, mainly (232)Th and (238)U series, and their decay products, as well as (40)K, which exist at trace levels in the earth's crust. Their concentrations in soil, sands, and rocks depend on the local geology of each region in the world. Naturally occurring radioactive materials generally contain terrestrial-origin radionuclides, left over since the creation of the earth. In addition, the existence of some springs and quarries increases the dose rate of background radiation in some regions that are known as high level background radiation regions. The type of building materials used in houses can also affect the dose rate of background radiations. The present review article was carried out to consider all of the natural radiations, including cosmic, terrestrial, and food radiation. PMID- 24223381 TI - Effects of different doses of doxepin on passive avoidance learning in rats. AB - BACKGROUND: Studies have shown that Doxepin has anti-inflammatory effects and reduces oxidative stress. Due to the fact that other tricyclic antidepressants have been shown to have neuroprotective effects, this study aimed to investigate the effects of different doses of doxepin on passive avoidance learning in rats. MATERIALS AND METHODS: Old male Wistar rats were used in this study. Doxepin was administered intraperitoneally (1, 5 and 10 mg/kg) for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock on fifteen day, and step through latencies were evaluated one week after the electrical shock in retention phase. RESULTS: Administration of Doxepin considerably increased the step through latencies in the rats that received the doses of 1 and 5 mg/kg (P < 0.05). However, in the dose of 10 mg/kg, there wasn't any significant change comparing to control group. CONCLUSION: These results indicate that Doxepin has desirable effects on cognitive functions in low doses. Therefore, Doxepin can be considered as memory enhancers that understanding the underling mechanisms need further investigation. PMID- 24223382 TI - The effect of L-arginine and L-NAME on myocardial capillary density in normal rats. AB - BACKGROUND: This study evaluated the effect of L-arginine (Nitric Oxide (NO) precursor) and L-NG-Nitroarginine Methyl Ester (L-NAME) (NO synthase inhibitor) on myocardial capillary density in normal rats. MATERIALS AND METHODS: EIGHTEEN MALE RATS WERE DIVIDED INTO THREE GROUPS: Group 1: Received L-NAME (10 mg/kg/day; ip), Group 2: Received L-arginine (50 mg/kg/day; ip), and Group 3 (control) received normal saline. After 3 weeks, blood samples were taken and myocardial capillary density was evaluated using immunohistochemistry method. RESULTS: Serum NO concentration in control group was 6.45 +/- 0.44 MUmol/lit. Treatment of animals with L-arginine increased serum NO concentration (7.90 +/- 0.75 vs. 6.45 +/- 0.44 MUmol/lit, respectively) and L-NAME decreased (4.86 +/- 0.40 vs. 6.45 +/ 0.44 MUmol/lit, respectively) compare to control group. L-arginine significantly increased serum vascular endothelial growth factor (VEGF) concentration (353.01 +/- 7.03 vs. 100.5 +/- 6.61 pg/ml; P < 0.05), however, did not change myocardial capillary density. CONCLUSION: Although L-arginine alters some serum angiogenic factors, either L-arginine or L-NAME could not improve myocardial capillary density in normal rats. PMID- 24223383 TI - Preemptive subcutaneous tramadol for post-operative pain in lower abdomen surgeries: A randomized double blinded placebo-control study. AB - BACKGROUND: Recently, the preemptive analgesic effects of subcutaneous infiltration of tramadol (T) in the site of incision have not been extensively studied. In this study, we investigated the effect of subcutaneous T infiltration before the incision of surgery on post-operative pain, in lower abdomen surgeries. MATERIALS AND METHODS: This double-blind study was carried out on 90 patients (18-65 years) of American Society Anesthesiologists physical status I and II who were candidates for a lower abdomen surgery during 2011. They were randomly assigned to receive preemptive subcutaneous T or normal saline (NS). The visual analogue scale for pain (VAS) in rest and cough position and opium total dose consumption were compared between two groups in times 0, 15, 30, 60 min and 2, 4, 6, 12, 24 h after the surgery. RESULTS: The VAS in cough and rest position in the first 24 h following the surgery was lower in group T (P < 0.05). Opium consumption was lower in group T (P < 0.05). CONCLUSION: Subcutaneous preemptive infiltration of T before surgical incision reduces post-operative opioid consumption. PMID- 24223384 TI - The comparison of the complications of axillobrachial and femorofemoral arteriovenous shunt prostheses in hemodialysis, a 3 year study in Alzahra general hospital. AB - BACKGROUND: This study was performed to compare the outcome and complications of axillobrachial and femorofemoral graft as upper and lower limb arteriovenous shunt prostheses. MATERIALS AND METHODS: In a prospective cohort study, we observed and followed-up all cases with a new insertion of ePTFE between February 2006 and February 2009. Assessment of patency and the complication rates of their prostheses were the essential parts of this observation. METHODS: In a prospective cohort study, we observed and followed-up all cases with a new insertion of ePTFE between February 2006 and February 2009. Assessment of patency and the complication rates of their prostheses were the essential parts of this observation. RESULTS: A total of 69 grafts were performed. Forty-nine of them were successfully followed-up (18 femorofemoral and 31 axillobrachial grafts). Immediate primary patency was 100%. For axillobrachial type, primary patency at 1, 3, and 6 months, respectively, was 86%, 60%, and 47%. Secondary patency at 1, 3, and 6 months was 86%, 75%, and 50%, respectively. For femorofemoral type, primary patency at 1, 3, and 6 months, respectively, was 88%, 40%, and 34%. Secondary patency at 1, 3, and 6 months was 94%, 47%, and 41%, respectively. (P > 0.05) Complications included a puncture-site hematoma, thrombosis, infection, venous hypertension, need of an excision and pseudoaneurysm formation. Pseudoaneurysm rate difference between the two groups was interestingly significant, while others were relatively similar; however, the rates were different. CONCLUSION: The significant difference of aneurysm rate among our two groups, besides the insignificant difference of other complications and also the similar primary and secondary patency rates, manifest a brilliant guidance chart for the surgeons in order to choose the most compatible site for inserting ePTFE grafts (Gore-tex) as arteriovenous shunt prostheses for HD accessing. PMID- 24223385 TI - Cavernous lymphangiomas involving bilateral labia major after caesarian section. PMID- 24223386 TI - Reasons for failure of immunization: A cross-sectional study among 12-23-month old children of Lucknow, India. AB - BACKGROUND: Roughly 3 million children die every year of vaccine preventable diseases and a significant number of these children live in developing countries. The present study was conducted to assess the reasons for failure of immunization among 12-23-month-old children of Lucknow city in India. MATERIALS AND METHODS: Out of all villages in rural areas and mohallas in urban areas of Lucknow district, eight villages and eight mohallas were selected by simple random sampling. A community based cross-sectional study was done among 450 children aged 12-23 months. The immunization status of the child was assessed by vaccination card and by mother's recall. A pre-designed and pre-tested questionnaire was used to elicit information on reasons for failure of immunization. Data was analysed using statistical package for social services (SPSS) version 11.5. Chi square test was used to find out the significant association. RESULTS: Overall, 62.7% children were fully immunized, 24.4% children were partially immunized, and 12.9% children were not immunized. The major reasons for failure of immunization were postponing it until another time, child being ill and hence not brought to the centre for immunization, unaware of the need of immunization, place of immunization being too far, no faith in immunization, unaware of the need to return for 2(nd) and 3(rd) dose, mother being too busy, fear of side reactions, wrong ideas about immunization, and polio was considered only vaccine, and others. CONCLUSION: More awareness should be generated among the people living in rural and urban areas to immunize their children. PMID- 24223387 TI - Design, formulation and evaluation of caffeine chewing gum. AB - BACKGROUND: Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. MATERIALS AND METHODS: Caffeine gum was prepared by softening of gum bases and then mixing with other formulation ingredients. To decrease the bitterness of caffeine, sugar, aspartame, liquid glucose, sorbitol, manitol, xylitol, and various flavors were used. Caffeine release from gum base was investigated by mechanical chewing set. Content uniformity test was also performed on the gums. The gums were evaluated in terms of organoleptic properties by the Latin-Square design at different stages. RESULTS: After making 22 formulations of caffeine gums, F11 from 20 mg caffeine gums and F22 from 50 mg caffeine gums were chosen as the best formulation in organoleptic properties. Both types of gum released about 90% of their own drug content after 30 min. Drug content of 20 and 50 mg caffeine gum was about 18.2-21.3 mg and 45.7-53.6 mg respectively. CONCLUSION: In this study, 20 and 50 mg caffeine gums with suitable and desirable properties (i.e., good taste and satisfactory release) were formulated. The best flavor for caffeine gum was cinnamon. Both kinds of 20 and 50 mg gums succeeded in content uniformity test. PMID- 24223388 TI - Study of the prevalence of azoospermia in patients with Hodgkin's lymphoma prior to treatment. AB - BACKGROUND: Infertility is one of the main problems of patients with Hodgkin's lymphoma, as this causes specific effects in the social, family, and emotional life of patients. Hodgkin's lymphoma is a neoplastic disorder that comprises of 0.6% of all cancers and often occurs in middle-aged people, with a mean age of 26 years. It originates from neoplastic changes in the lymphoid cells, which lead to different complications in the body organs. One important complication of Hodgkin's lymphoma is humoral and cellular immune system dysfunction that can cause numerous and dangerous problems for patients. Another complication of Hodgkin's lymphoma is sterility, more specifically hypogonadism and azoospermia. Sterility may appear after treatment. Considering that most patients with Hodgkin's lymphoma have a good survival, diagnosing and treating this complication and preventing its incidence contributes to improving the quality of social life and emotional status of these patients. MATERIALS AND METHODS: In this study, 238 patients whose Hodgkin's lymphoma was approved by Pathology were included in the study, before receiving any medical intervention, and they were examined for sterility (sperm status). Sterility of the male patients was confirmed using a spermogram test. The serum levels of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were checked. RESULTS: Among the studied patients, 24 patients (10.08%) suffered from azoospermia, which was evident in its progressive stages. CONCLUSION: In such cases, treatment of Hodgkin's lymphoma and improvement of the immune system could overcome azoospermia and sterility. PMID- 24223389 TI - A rare case of laryngotracheal chondrosarcoma in a patient with past history of radioiodine therapy for thyroid cancer. AB - Tracheal chondrosarcoma is a rare malignant mesenchymal tumor and there are less than 15 reports in the literature. We report a rare case of laryngotracheal chondrosarcoma in a 74-year-old man. He gave a history of radioiodine therapy for thyroid papillary carcinoma about 24 years ago. Diagnostic steps, histological presentation, and therapy are described in detail. PMID- 24223390 TI - Evaluation on the responses of succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and glucose-6-phosphate dehydrogenase to acid shock generated acid tolerance in Escherichia coli. AB - BACKGROUND: Escherichia coli have an optimum pH range of 6-7 for growth and survival that's why, called neutrophiles. The DeltapH across the cytoplasmic membrane is linked to cellular bioenergetics and metabolism of the body which is the major supplier of the proton motive force, so homeostasis of cellular pH is essential. When challenged by low pH, protons enter the cytoplasm; as a result, mechanisms are required to alleviate the effects of lowered cytoplasmic pH. MATERIALS AND METHODS: The activities of Succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and glucose-6-phosphate dehydrogenase in acid shocked cells of E. coli DH5 alpha and E. coli W3110 subjected to pH 3, 4, and 5 by two types of acidification, like external (using 0.1 N HCl), external along with the monensin (1 MUM) and cytoplasmic acidification using the sodium benzoate as an acid permeant (20 mM) which is coupled to the electron transport chain by the reducing power, as yet another system possessed by E. coli as an armor against harsh acidic environments. RESULT: Results showed that an exposure to acidic environment (pH 3, 4 and 5) for a short period of time increased the activities of these dehydrogenases in all types of acidification except cytoplasmic acidification, which shows that higher recycling of reducing power results in pumping out of protons from the cytoplasm through the electron transport chain complexes, thereby restoring the cytoplasmic pH of the bacteria in the range of 7.4-7.8. CONCLUSION: Study indicates that acid shocked E. coli for a period of 2 h can survive for a sustained period. PMID- 24223391 TI - Comparison of therapeutic effect of low-dose low-molecular-weight heparin (enoxaparin) vs. oral prednisone in treatment of patients with lichen planus; A clinical trial. AB - BACKGROUND: The aim of this study was to evaluate and compare the therapeutic efficacy of subcutaneous enoxaparin versus oral prednisone (as a standard treatment) in patients with disseminated lichen planus. MATERIALS AND METHODS: In this parallel randomized clinical trial study, overall 48 patients completed the study. 25 patients were treated with subcutaneous enoxaparin 5 mg weekly and 23 patients with 0.5 mg/kg prednisone orally daily until complete remission or a maximum of 8 weeks. The results of itching severity, extent of active lesions and drug side effects were compared. In remission, patients were followed for 6 months for recurrent lesions. RESULTS: In enoxaparin group, 8 patients (32%) had complete remission and 10 patients (40%) had partial improvement. In the oral prednisone group, 16 patients (69.6%) had complete remission and 6 patients (26.1%) had partial improvement (P = 0.005). Average size of active lesions in both groups decreased significantly after treatment, but analysis of covariance showed that the mean lesion size after treatment in the oral prednisone group was significantly lower than the enoxaparin group (P = 0.005). The relapse rate from improved patients in the enoxaparin group was 6 (33%) and in oral prednisone group was 9 (40.9%, P = 0.083). In the enoxaparin group no serious complications was seen. But 22% in the oral prednisone group show side effect, the most common complications were dyspepsia. CONCLUSION: Low dose enoxaparin on lichen Planus have therapeutic effect and is important for the least side effects but not as much as oral prednisone. But it could be accepted as an alternative treatment. PMID- 24223392 TI - Evaluation and comparison of zinc absorption level from 2-Alkyle 3-Hydroxy pyranon-zinc complexes and zinc sulfate in rat in vivo. AB - BACKGROUND: Although zinc sulfate has been used to improve disorders originated from zinc deficiency, its low compliance is due to gastrointestinal complications; therefore, other zinc compounds have been suggested as replacers for zinc deficient people. The objective of this study was to evaluate and compare the absorption of ethyl and methyl zinc-maltol with that of zinc sulfate to substitute zinc sulfate with those complexes. MATERIALS AND METHODS: After five weeks of being fed by zinc deficient food, zinc deficient rats were divided into four groups randomly receiving medicinal solutions of zinc sulfate, zinc ethyl maltol and zinc methyl maltol using feeding tube method for two weeks while the control was received distilled water. Serum zinc concentration and ALP (Alkaline Phosphatase) and LDH (Lactate Dehydrogenase) activity of rats were determined before and after the study. Statistical analyses were performed using SPSS 11.5. The study was conducted from 2008 to 2010. RESULTS: Serum zinc concentration and enzyme activity in all groups receiving drug solution increased. The most and least increase were in zinc sulfate and zinc methyl maltol groups, respectively. The difference between zinc methyl maltol and zinc sulfate group was significant (P < 0.05); however, this difference was not significant in the case of zinc ethyl maltol. CONCLUSION: Zinc ethyl maltol can be a suitable and preferable substitute for zinc sulfate. PMID- 24223393 TI - Prostate International, an international academic forum on prostate diseases. PMID- 24223394 TI - Letter to the editor. PMID- 24223396 TI - Androgen receptor coactivator p120 subtype beta is highly expressed in prostate cancer. AB - PURPOSE: The beta form of p120 is reported to be a strong coactivator of the androgen receptor. We investigated the gene expression profiles of the alpha and beta forms of p120 in prostate cancer cell lines, benign prostatic hyperplasia (BPH), nontreated prostate cancer (NTPC), and prostate cancer after androgen deprivation therapy (PCA-ADT). METHODS: We obtained 154 prostate needle biopsy specimens (81 in BPH, 51 in NTPC, and 22 in PCA-ADT). Levels of p120alpha and beta expression were determined by multiplex real-time polymerase chain reaction. RESULTS: Prostate cancer cell lines, LNCaP, PC-3, DU-145, and LNCaP-LA, which is a derivative of LNCaP under androgen deprivation, expressed both p120alpha and p120beta. p120alpha expression levels were significantly higher than those of p120beta in all cell lines examined. In human prostate tissues, p120alpha expression was significantly higher than that of p120beta in BPH and NTPC. p120alpha expression in BPH was significantly higher than in other groups. In contrast, p120beta expression was significantly higher in NTPC and PCA-ADT than in BPH. Expression of the two forms of p120 was not correlated with age, prostate specific antigen, or Gleason score. CONCLUSIONS: The expression profiles of p120alpha and p120beta significantly differ in cancerous and benign prostatic tissues. PMID- 24223395 TI - MicroRNAs in prostate cancer. AB - MicroRNAs (miRNAs) are made up of -22 endogenous nucleotides and are small, noncoding RNAs that are important regulators of gene expression at the posttranscriptional level by degrading or repressing target miRNAs. miRNA expression profiles can be used for the detection of diagnostic and prognostic markers for various cancers. Also, alterations of miRNAs in cancer tissues have been associated with clinicopathological parameters. Along with circulating miRNAs, tissue miRNAs have shown promise as markers that can predict cancer recurrence and/or the potential for survival of cancer patients. Additionally, some miRNAs have therapeutic potential. In this review, we discuss and assess the usefulness of tissue-derived and circulating miRNAs for the diagnosis and prognosis of prostate cancer. PMID- 24223397 TI - Outcomes and predictors of localized or locally-advanced prostate cancer treated by radiotherapy in Indonesia. AB - PURPOSE: Presently there is no published data on the outcomes of localized or locally-advanced prostate cancer (PCa) treated by external-beam radiotherapy (RT) in Indonesia. METHODS: This study retrospectively analyzed 96 patients with localized or locally-advanced PCa treated by RT from year 1995 to 2009, at the national referral hospital and the national cancer hospital of Indonesia. Cumulative prostate and pelvic radiation dose/type was <70 Gy conventional RT in 84.4% patients, and >=70 Gy Three dimensional-conformal or intensity modulated RT in 15.6% patients. Overall survival (OS) and biochemical progression-free survival (BFS) were estimated by Kaplan-Meier. Predictors of OS and biochemical recurrence were analyzed by multivariate Cox regressions. RESULTS: The median follow-up was 61 months (range, 24 to 169 months). There were 3.1% low-risk, 26% intermediate-risk, and 70.8% high-risk cases. More than half of the patients (52.1%) had pretreatment prostate-specific antigen (PSA) >20 ng/mL. The 5-year survival outcome of low-risk, intermediate-risk, and high-risk patients were: OS, 100%, 94.7%, and 67.9% (P=0.297); and BFS, 100%, 94.1%, and 57.1% (P=0.016), respectively. In the high-risk group, the 5-year OS was 88.3% in patients who received adjuvant hormonal androgen deprivation therapy (HT), compared to 53% in RT only, P=0.08. Significant predictors of OS include high-risk group (hazard Ratio [HR], 9.35; 95% confidence interval [CI], 1.52 to 57.6; P=0.016), adjuvant therapy (HR, 0.175; 95% CI, 0.05 to 0.58; P=0.005), detection by transurethral resection of the prostate (TUR-P) (HR, 6.81; 95% CI, 2.28 to 20.33; P=0.001), and pretreatment PSA (HR, 1.003; 95% CI, 1.00 to 1.005; P=0.039). The sole predictor of biochemical failure was pretreatment PSA (P=0.04), with odds ratio of 4.52 (95% CI, 1.61 to 12.65) for PSA >20 ng/mL. CONCLUSIONS: RT is an effective treatment modality for localized or locally-advanced PCa in Indonesian patients, with outcomes and predictors consistent to that reported elsewhere. Predictors of poorer outcomes include high-risk group, higher pretreatment PSA, incidental detection by TUR-P, and lack of adjuvant HT. Adjuvant hormonal therapy significantly improve the survival of high risk patients. PMID- 24223398 TI - Prostate-specific antigen and prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer. AB - PURPOSE: Racial differences exist in the incidence of prostate cancer (PCa). Although many studies have looked at the performance of prostate-specific antigen (PSA) and PSA density (PSAD) in the detection of PCa, only a few have looked at it in relation to Indonesian men. The objective of this study is to find out better PSA and PSAD cutoff point in the detection of PCa in Indonesian men. METHODS: A total of 404 consecutive Indonesian men underwent prostate biopsy for suspicion of PCa from 2008 to 2011. The biopsy criteria include one or more of the following: serum PSA more than 10 ng/mL, PSAD more than 0.15 if PSA 4-10 ng/mL, hypoechoic lesion during transrectal sonography and/or abnormal digital rectal examination. RESULTS: Forty five out of 404 (11.1%) had positive biopsies. The mean age, prostate volume, PSA and PSAD were respectively 64.06 years, 43.03 mL, 45.59 ng/mL and 1.15. Of the 404, 131 cases (32.4%) were confirmed to be urinary retention. Positive urine culture found in 182 cases (45%). The cutoff point to detect PCa as estimated by the receiver operating characteristics was 6.95 ng/mL for PSA (sensitivity 97.8%, specificity 19.6%) and 0.7072 for PSAD (sensitivity 62.2%, specificity 78.7%). Positive predictive value for this PSA and PSAD cutoff point were 11.6% and 27.5% respectively (P=0.004 and P=0.000). There was a significant correlation between hypoechoic lesion and positive biopsy results (P =0.000). Urinary retention elevates PSA cutoff point to 14.55 (sensitivity 90.9%, specificity 50%), while positive urine culture alters almost no PSA cutoff elevation. CONCLUSIONS: PSA and PSAD cutoff point for Indonesian men in this series is relatively different from international consensus. Furthermore, these data show that PSA and PSAD cutoff point must be adjusted to racial variation to discriminate between malignant and benign disease. Urinary retention is a significant factor for PSA cutoff increase. PMID- 24223399 TI - Robotic-assisted prostatectomy and open radical retropubic prostatectomy for locally-advanced prostate cancer: multi-institution comparison of oncologic outcomes. AB - PURPOSE: Robotic-assisted laparoscopic prostatectomy (RALP) offers reportedly comparable oncologic outcomes for localized disease compared with open radical retropubic prostatectomy (ORRP). However, the oncologic efficacy of RALP in locally-advanced prostate cancer (PCa) is less clear. We report and compare our experience with RALP and ORRP in men with locally advanced PCa. METHODS: Patients with locally advanced PCa (stage T3 or greater) were identified in both robotic and open cohorts. Clinicopathologic features including age, clinical stage, prostate-specific antigen, surgical margins, and Gleason score were reviewed. We further examined the incidence of positive surgical margins, the effect of the surgical learning curve on margins, and the need for adjuvant therapy. RESULTS: From 1997 to 2010, 1,011 patients underwent RALP and 415 patients were identified who underwent radical retropubic prostatectomy (RRP) across four institutions. 140 patients in the RALP group and 95 in the RRP group had locally advanced PCa on final pathology. The overall robotic positive margin rate 47.1% compared with 51.4% in the RRP group. A trend towards a lower positive margin rate was seen after 300 cases in the RALP group, with 66.7% positive margin rate in the first 300 cases compared with 41.8% in the latter 700 cases. In addition, a lower incidence of biochemical recurrence was also noted in the latter cases (30.6% vs. 9.5%). CONCLUSIONS: Up to 2 out of 3 men undergoing RALP for locally-advanced PCa had positive margins during our initial experience. However, with increasing surgeon experience the overall positive margin rate decreased significantly and was comparable to the positive margin rate for patients with locally advanced disease undergoing ORRP over four academic institutions. We also noted a lower incidence of biochemical recurrence with increasing RALP experience, suggesting better oncologic outcomes with higher volume. Given this data, RALP has comparable oncologic outcomes compared to ORRP, especially with higher volume surgeons. PMID- 24223400 TI - Efficacy and safety of low-dose anticholinergics to treat men with lower urinary tract symptoms with overactive bladder: a retrospective study based on real life practice. AB - PURPOSE: To investigate whether combination treatment using an alpha-blocker and 2 mg of tolterodine could improve the International Prostate Symptom Score (IPSS) as much as alpha-blocker and 4 mg of tolterodine without voiding difficulties in real life practice. METHODS: We restrospectively recruited patients who were treated at four urology clinics between January 2006 and May 2008. A total of 1,094 men with lower urinary tract symptoms/overactive bladder (LUTS/OAB) were assigned to one of three groups: an alpha-blocker only group (group I, n=152), an alpha-blocker plus tolterodine 2 mg group (group II, n=520), and an alpha-blocker plus tolterodine 4 mg group (group III, n=574). Eligible patients were 50 years or older men who had a total IPSS of 8 or higher and a IPSS storage subscore of 5 or higher and were followed up for 12 weeks. RESULTS: The total IPSS score and quality of life scores were significantly improved at week 12 in groups II and III. The incidence of acute urinary retention was similar between both combination treatment groups, but the incidence of voiding difficulty was much lower in group II (2.1%) than group III (10.8%) tolterodine. CONCLUSIONS: Our results suggest that treatment of LUTS/OAB patients with an alpha-blocker plus tolterodine 2 mg is as effective as alpha-blocker plus tolterodine 4 mg, and the incidence of voiding difficulty was in the low-dose anticholinergic is lower. These results indicate that dose strength should be decided on a case-by-case basis to balance the efficacy and safety. PMID- 24223401 TI - Early experience photoselective vaporisation of the prostate using the 180W lithium triborate and comparison with the 120W lithium triborate laser. AB - PURPOSE: There is a paucity of information on the clinical efficacy and safety of the photoselective vaporization (PVP) of the prostate using the 180W lithium triborate (LBO) laser. We report on initial outcomes of PVP with the 180W laser, comparing the first 50 cases with the last 50 cases performed with the 120W LBO laser. METHODS: All cases performed by a single surgeon (HHW) have been prospectively maintained. The last 50 cases treated with the 120W LBO laser (December 2009 to August 2010) were compared with the first 50 cases treated with the 180W LBO (July 2010 to June 2011). Patient variables were recorded preoperatively and at 3 months postoperatively. Perioperative data was also recorded. RESULTS: The 180W cases had a larger median transrectal ultrasound prostate volume (68 mL vs. 51 mL, P<0.05). For the 180W and 120W LBO lasers, total operating time was 64.2 and 72.5 minutes (not significant [NS] at P=0.22), lasering time 49.6 and 54.6 minutes (NS, P=0.30) and energy utilisation 477.6 kJ and 377.9 kJ (P<0.05) respectively. When compared per gram of prostate tissue lasered, the 180W is quicker at 0.67 min/g vs. 1.0 min/g for the 120W laser. Complications using the Clavien-Dindo classification included 5 grade 1 complications and 3 grade 3b (bladder neck contractures) with the 180W LBO laser. The 120 W LBO laser had 4 grade 1 complications and 1 grade 2. CONCLUSIONS: There is little change in clinical outcomes with the transition from 120W to 180W LBO PVP with an already experienced PVP surgeon. The 180W LBO laser appears to have impacted upon patient selection with significantly increased prostate size and associated with increased energy utilisation. There appears to be a trend toward shorter laser times. PMID- 24223402 TI - Epidemiology of prostate cancer in the Asia-Pacific region. AB - The purpose of this paper was to examine and compare available data on incidence, mortality and survival for countries in the Asia-Pacific region. Incidence data were obtained from GLOBOCAN 2008, other online data sources and individual cancer registries. Country-specific mortality statistics by individual year were sourced from the World Health Organization Statistical Information System Mortality Database. All incidence and mortality rates were directly age-standardised to the Segi World Standard population and joinpoint models were used to assess trends. Data on survival were obtained from country-specific published reports where available. Approximately 14% (122,000) of all prostate cancers diagnosed worldwide in 2008 were within the Asia-Pacific region (10 per 100,000 population), with three out of every four of these prostate cancer cases diagnosed in either Japan (32%), China (28%) or Australia (15%). There were also about 42,000 deaths due to prostate cancer in the Asia-Pacific region (3 per 100,000). For the nine countries with incidence trend data available, eight showed recent significant increases in prostate cancer incidence. In contrast, recent decreases in prostate cancer mortality have been reported for Australia, Japan and New Zealand, but mortality has increased in several other countries. The lack of population-based data across most of the countries in this region limits the ability of researchers to understand and report on the patterns and distribution of this important cancer. Governments and health planners typically require quantitative evidence as a motivation for change. Unless there is a widespread commitment to improve the collection and reporting of data on prostate cancer it is likely that the burden of prostate cancer will continue to increase. Enhancing knowledge transfer between countries where there are differentials in capacity, policy and experience may provide the necessary impetus and opportunity to overcome at least some of the existing barriers. PMID- 24223403 TI - Development of prostate cancer research database with the clinical data warehouse technology for direct linkage with electronic medical record system. AB - PURPOSE: In spite of increased prostate cancer patients, little is known about the impact of treatments for prostate cancer patients and outcome of different treatments based on nationwide data. In order to obtain more comprehensive information for Korean prostate cancer patients, many professionals urged to have national system to monitor the quality of prostate cancer care. To gain its objective, the prostate cancer database system was planned and cautiously accommodated different views from various professions. METHODS: This prostate cancer research database system incorporates information about a prostate cancer research including demographics, medical history, operation information, laboratory, and quality of life surveys. And, this system includes three different ways of clinical data collection to produce a comprehensive data base; direct data extraction from electronic medical record (EMR) system, manual data entry after linking EMR documents like magnetic resonance imaging findings and paper-based data collection for survey from patients. RESULTS: We implemented clinical data warehouse technology to test direct EMR link method with St. Mary's Hospital system. Using this method, total number of eligible patients were 2,300 from 1997 until 2012. Among them, 538 patients conducted surgery and others have different treatments. CONCLUSIONS: Our database system could provide the infrastructure for collecting error free data to support various retrospective and prospective studies. PMID- 24223404 TI - Trends of clinical symptoms and prognosis of middle-aged prostate cancer patients after instigation of prostate specific antigen-based population screening. AB - PURPOSE: Due to the low rate of screening for prostate cancer in Japan, the incidence rates of cancer are high. We have established a prostate-specific antigen (PSA)-based screening system for prostate cancer in our region. We analyzed recent trends of clinical symptoms and prognosis of prostate cancer patients aged 55 to 69 years old in our institution. METHODS: Between 2000 and 2007, 162 cases of prostate cancer in patients aged 55 to 69 years old were newly diagnosed. The study population was divided into 119 cases with high PSA without symptoms, 36 cases with urological symptoms, and 7 cases with systemic symptoms. We analyzed the clinical courses of the patients in each group. RESULTS: The rate of localized disease was significantly higher in the PSA testing group than in the other groups. The median serum PSA levels were 1,600 ng/mL in the systemic symptom group, 13.3 ng/mL in the urological symptom group, and 7.1 ng/mL in the PSA testing group. The probability of nonrecurrence of the patients in the PSA testing group was significantly higher than in the other groups. CONCLUSIONS: The rate of prostate cancer patients diagnosed by PSA testing was relatively high in our institution. These patients have better prognosis than those with symptoms. PMID- 24223405 TI - Nomogram using transrectal ultrasound-derived information predicting the detection of high grade prostate cancer on initial biopsy. AB - PURPOSE: To develop a nomogram using transrectal ultrasound (TRUS)-derived information for predicting high grade (HG) prostate cancer (PCa) on initial biopsy. METHODS: Data were collected on 1,048 men with serum prostate-specific antigen (PSA) levels 4.0 to 9.9 ng/mL who underwent an initial prostate biopsy. Two logistic regression-based nomograms were constructed to predict the detection of PCa. Nomogram-1 incorporated age, digital rectal examination, PSA and percent free PSA data, whereas nomogram-2 incorporated those factors plus TRUS-derived information (i.e., prostate volume and the presence of hypoechoic lesions). The prediction of any PCa and HGPCa (Gleason score>=7) were determined. Twenty percent of the data were randomly reserved for study validation, and the predictive accuracies of the two nomograms were directly compared. RESULTS: Of the 1,048 men who underwent biopsy, 216 (20.6%) were found to have any PCa, and 97 (9.3%) were found to have HGPCa. All six risk factors were found to be independent predictors for both any PCa and HGPCa. The area under curve (AUC) for nomogram-2 was 0.76 (95% confidence interval [CI], 0.72 to 0.81) for predicting any PCa, and 0.83 (95% CI, 0.79 to 0.88) for predicting HGPCa. These AUCs were greater than those for nomogram-1 (0.72 [95% CI, 0.68 to 0.76 for any PCa; P<0.001], 0.78 [95% CI, 0.72 to 0.83 for HGPCa; P<0.001]). Removing the TRUS derived information from nomogram-2 resulted in an incremental AUC decrease of 0.052 for any PCa and 0.063 for HGPCa. CONCLUSIONS: The nomogram using TRUS derived information had a high predictive accuracy for HGPCa on initial prostate biopsy. PMID- 24223406 TI - Simple method for preventing inguinal hernias after radical retropubic prostatectomy. AB - PURPOSE: Inguinal hernias often occur after radical retropubic prostatectomy (RRP). We present a novel and simple technique for preventing inguinal hernias after RRP, which any surgeon can complete within a few minutes. METHODS: A total of 230 Japanese prostate cancer patients underwent RRP between January 2007 and September 2011. From July 2009, 115 patients underwent inguinal hernia prevention procedures at the same time as RRP. In this procedure, we released approximately 5 cm of the bilateral vas deferens and spermatic vessels from the peritoneum. In cases in which the processus vaginalis had spread into the abdomen, we ligated it close to the peritoneal cavity and then transected it. The remaining 115 patients who underwent RRP but did not undergo the hernia prevention procedure were used as the control group. The incidence rate of postoperative inguinal hernia was compared between the 2 groups. RESULTS: Inguinal hernias developed during the postoperative follow-up period in 18 of the 115 control patients (15.7%) (median duration, 50 months). The hernia-free survival rate of this group was 89.6% and 84.1% at 1 and 2 postoperative years, respectively. In contrast, only 1 of the 115 patients (0.87%) who underwent the hernia prevention procedure developed an inguinal hernia during the follow-up period (median duration, 27 months). The hernia-free survival rate of this group was 100% at both 1 and 2 postoperative years (P<0.0001). CONCLUSIONS: We developed a simple method for preventing post RRP inguinal hernias. The procedure is easy to perform and produces excellent outcomes. PMID- 24223407 TI - Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score. AB - PURPOSE: To determine the influence of maximal androgen blockade (MAB) and non MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. METHODS: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. RESULTS: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (>=75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. CONCLUSIONS: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID- 24223408 TI - Clinical courses following acute bacterial prostatitis. AB - PURPOSE: There are few studies about clinical courses following acute bacterial prostatitis (ABP). We evaluated the progression rates of chronic bacterial prostatitis (CBP) and inflammatory chronic pelvic pain syndrome (CPPS) after ABP treatment. Also evaluated the characteristics of the patients who developed CBP and inflammatory CPPS after ABP treatment. METHODS: Total 437 patients compatible with a confirmed diagnosis of ABP from 5 urological centers between 2001 and 2010 were enrolled to study. We defined chronic infection (CI) as a progression to CBP and inflammatory CPPS after treatment of ABP in admission periods when followed up at 3 months or more. Results were analyzed between two groups: recovered without CI (group A, n=385) and developed to CI (group B, n=52). RESULTS: Of the 437 ABP patients, 1.3% (6/437) progressed to CBP and 10.5% (46/437) progressed to inflammatory CPPS. The progression rate of CI was 11.8% (52/437). The patients who developed to CI were higher in alcohol consumption rate, diabetes, voiding symptoms, prior manipulation rate, enlarged prostate volume, catheterization history rate and short duration of antibiotic treatment (P<0.05). CONCLUSIONS: The identification and characterization of these factors may accelerate the development of preventive, diagnostic and therapeutic strategies for the treatment of CI from ABP. PMID- 24223409 TI - The role of radical prostatectomy in high-risk prostate cancer. AB - Because of the increase in prostate cancer patients, urologists can detect more clinically localized prostate cancer in patients before the disease has progressed to advanced stages. Nevertheless, some patients are still diagnosed with high-risk prostate cancer. Even though several treatment options are available for high-risk prostate cancer patients, including radical prostatectomy, radiotherapy, and hormone therapy, used alone or in combination, the recurrence rate is high regardless of the type of treatment. Nevertheless, in the experience of many urologists, a substantial proportion of high-risk prostate cancer patients are cured by local definite therapy or multimodality treatment. Thus, several treatment combinations have been attempted as treatments in these patients. Among them, radical prostatectomy is regarded as the first step in high risk prostate cancer patients, on a selective basis. In some high-risk prostate cancer patients, surgery is a one-step modality in treatment and has an excellent oncological prognosis. However, because of the lack of evidence and well controlled comparative prospective studies, the best course of treatment can be unclear, and oncological outcomes often appear heterogeneous. We therefore review the current literature on clinical outcomes in high-risk prostate cancer. PMID- 24223410 TI - Peripheral zone prostate-specific antigen density: an effective parameter for prostate cancer prediction in men receiving 5alpha-reductase inhibitors. AB - PURPOSE: To evaluate the predictive performance of various parameters derived from volume-adjusted prostate-specific antigen (PSA) values in detecting prostate cancer (PCa) and high-grade (Gleason score>=7) PCa according to treatment with a 5alpha-reductase inhibitor (5ARI). METHODS: The results of 3,520 prostate biopsies performed between May 2006 and January 2013 were retrospectively assessed. With adjustment for age, 291 patients who had received 5ARI treatment for more than 6 months were identified and matched 1:3 to patients naive to 5ARIs, resulting in a total of 873 patients. Peripheral zone (PZ) and transition zone (TZ) volumes were determined by transrectal ultrasonography. Receiver operating characteristic (ROC) curve analysis was used to compare predictive performances of PSA, PSA density (PSAD; PSA/prostate volume), PZPSAD (PSA/PZ volume), and TZPSAD (PSA/TZ volume) for detecting PCa and high-grade PCa for each group. RESULTS: The area under the ROC curve (AUC) was higher for PSAD than for PSA in the 5ARI group (0.751 vs. 0.677) and in the 5ARI-naive group (0.649 vs. 0.582), respectively (P<0.001). In the 5ARI group, the AUC for PZPSAD was even higher than that for PSAD (0.781 vs. 0.751, P=0.038); in the 5ARI-naive group, however, PZPSAD failed to achieve significant superiority (0.652 vs. 0.649, P=0.321). All volume-adjusted PSA indexes showed higher predictive accuracies for detecting PCa than did PSA in both groups. For detecting high-grade cancer, PZPSAD also revealed the highest predictive value in the 5ARI group, whereas PSA revealed the highest predictive value in the 5ARI-naive group. CONCLUSIONS: The diagnostic performance of PSAD in the detection of PCa is superior to that of PSA. For patients receiving 5ARI for more than 6 months, PZPSAD confers additional benefits for detecting both PCa and high-grade PCa. PMID- 24223411 TI - Serum level of follicle-stimulating hormone is associated with extraprostatic extension of prostate cancer. AB - PURPOSE: To determine whether serum follicle-stimulating hormone (FSH) can be used to predict the aggressiveness of prostate cancer prior to radical prostatectomy. METHODS: Ninety-six patients who underwent radical prostatectomy for biopsy proved cT1c-T2N0M0 prostate cancer between 2003 and 2008 were identified for retrospective analysis. Using univariate regression analysis, potential variables of extraprostatic tumor extension were identified, including prostate-specific antigen (PSA), luteinizing hormone, FSH, testosterone, biopsy findings, and age. These variables of interest were analyzed by logistic and linear regression analysis to determine if serum FSH is predictive of extraprostatic extension. RESULTS: Extraprostatic extension was pathologically confirmed in 18 of 96 patients (18.8%). Statistical analysis confirmed that serum FSH was significantly associated with extraprostatic extension (P=0.04). However, age, PSA level, Gleason score, number of tumors, and serum testosterone level were not found to be independent predictors of extraprostatic extension. CONCLUSIONS: Selective expression of FSH receptor on the surface of blood vessels of prostate cancers has recently been reported. Measuring serum FSH preoperatively in patients with prostate cancer may provide clinically relevant information about extraprostatic spread of tumor. PMID- 24223412 TI - Chlormadinone acetate is effective for hot flush during androgen deprivation therapy. AB - PURPOSE: To investigate the clinical efficacy of low-dose chlormadinone acetate (CMA) in prostate cancer patients who suffer from hot flushes that is a major side effect of androgen deprivation therapy. METHODS: Our study included 32 prostate cancer patients who had severe hot flush after undergoing hormone therapy for more than 3 months. The average age of the patients was 72.5 years. In the beginning, patients received CMA at 100 mg orally per day. We defined the hot flush as disappeared, improved, or not improved. In patients with disappeared or improved symptoms, we decreased CMA dose to 50 mg per day, and after we reevaluated the effect, we decreased CMA dose to 25 mg per day. When hot flush appeared again at 25 mg per day, we returned the dose of CMA to 50 mg per day. In cases with no change for more than two months, we canceled the treatment of CMA. RESULTS: Hot flush disappeared in 17 patients, improved in 10 patients, and did not improve in 5 patients (reduction in 84% of hot flush patients). The median time to hot flush reduction was 1.16 months. The effect of CMA was maintained at 25 mg per day in 19 patients and at 50 mg per day in 8 patients. No patients had prostate-specific antigen failure in the treatment of CMA. CONCLUSIONS: When hot flush appears during treatment with luteinizing hormone-releasing hormone agonist for prostate cancer, it seems that CMA can improve it immediately in most patients. PMID- 24223413 TI - Prospective longitudinal comparative study of health-related quality of life and treatment satisfaction in patients treated with hormone therapy, radical retropubic prostatectomy, and high or low dose rate brachytherapy for prostate cancer. AB - PURPOSE: To evaluate the effects of four different prostate cancer treatments on quality of life (QoL) and patient satisfaction. METHODS: Ninety-six prostate cancer patients were treated with hormone therapy, radical retropubic prostatectomy, high dose rate brachytherapy, or low dose rate brachytherapy. We assessed general, cancer-specific, and prostate disease-specific QoL. More than one year since commencement of treatment, the patients were asked the following questions: 1) How do you feel about your treatment? 2) Would you undergo the same treatment again? RESULTS: The comparison of baseline and 12-month results showed that general and cancer-specific QoL had changed little in all groups. At baseline, the general and cancer-specific QoL tended to be lower in the hormone therapy patients. In the radical the retropubic prostatectomy patients, all scores on the Medical Outcomes Study 36-Item Short Form were worse than the baseline scores at three months. Scores for the International Index of Erectile Function-5 had also worsened, with no recovery. In the low-dose rate brachytherapy patients, the prostate disease-specific QoL at baseline tended to improve. However, the satisfaction levels for each treatment were reasonably good, and most patients would choose the same treatment again. CONCLUSIONS: The results of each of the four treatments differed in assessments of QoL. In the radical retropubic prostatectomy patients, the decrease in the International Index of Erectile Function-5 scores was especially remarkable and did not show recovery. In contrast, both brachy therapy groups had attained superior sexual function. However, regardless of the quality of life evaluations, most patients surveyed were satisfied with their treatments and would choose the same treatment again. PMID- 24223414 TI - Prostate-specific antigen response rate of sequential chemotherapy in castration resistant prostate cancer: the results of real life practice. AB - PURPOSE: Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents. METHODS: We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center. RESULTS: In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed. CONCLUSIONS: Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC. PMID- 24223415 TI - Microbiological etiology of bacterial prostatitis in general hospital and primary care clinic in Korea. AB - PURPOSE: The National Institutes of Health classification of prostatitis reported the proportion of chronic bacterial prostatitis, especially category II, at 3% to 10%. Because of the polymerase chain reaction (PCR) diagnosis technique, chronic prostatitis syndrome (CPS) with a known bacterial origin has increased recently. In this study, we evaluated the proportion of chronic bacterial prostatitis in a general hospital and a primary care clinic (PCC) in addition to the distribution of the microorganism in chronic bacterial prostatitis in Korea. METHODS: Two hundred and ninety-three patients were enrolled in this study. One hundred and five patients in the general hospital and 188 patients in the PCC were enrolled in the study. Using a questionnaire, all patients were checked for symptoms of urinalysis, expressed prostate secretion (EPS), EPS or V3 culture and PCR of EPS or VB3 for Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genetalia, and Trichomatis vaginalis. RESULTS: In routine EPS or VB3 culture, 12 of 105 patients (11.4%) in the general hospital showed positive culture, but 77 of 188 patients (40.9%) in the PCC showed a positive culture. Escherichia coli, Streptococcus faecalis, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus aureus, and Pseudomonas were isolated in routine culture. In the PCR diagnosis, 37 of 105 patients (35.2%) in the general hospital were PCR positive, and 65 of 188 patients (34.5%) in the PCC were PCR positive. In the general hospital, C. trachomatis was the most common (49%), followed by U. urealyticum (24%), M. genetalia (16%), M. hominis (10%), and T. vaginalis (2%). In the PCC, U. urealyticum was the most common (45%), followed by C. trachomatis (34%), M. hominis (13%), M. genetalia (7%) and T. vaginalis (1%). The proportions of chronic bacterial prostatitis were 46.6% (49/105) and 67.5% (127/188) in the general hospital and PCC, respectively. CONCLUSIONS: The total portion of chronic bacterial prostatitis was 59.3% (174/293). Culture-positive patients in the PCC were significantly higher than in the general hospital, but the number of PCR positive patients in the PCC was the same as in the general hospital. PMID- 24223416 TI - Influence of the resin cement thickness on bond strength and gap formation of fiber posts bonded to root dentin. AB - PURPOSE: To evaluate the effect of the resin cement thickness (RCT) on bond strength (BS) and gap formation (GF) of fiber posts bonded to root dentin. MATERIALS AND METHODS: The roots of 24 extracted human mandibular premolars were treated endodontically and the post spaces were prepared using drills with different diameters according to the following groups (n = 8): well adapted (WA), moderately well adapted (MA) and poorly adapted (PA). The fiber glass posts were cemented (Excite DSC and Variolink II) in accordance with the manufacturer's instructions. After 1 week, the roots were transversely sectioned into six 1-mm thick disks and photographed using an optical microscope to determine the RCT. After this, epoxy resin replicas of each sample were observed using SEM, and the mean length and width of the gaps formed in the cement/dentin/post interface were measured. Finally, each sample was subjected to the push-out test (0.5 mm/min), and the data were statistically analyzed using one-way ANOVA and Tukey's tests at the 5% level of significance. RESULTS: The lowest RCT (MUm) was observed for WA and the highest for PA. The group MA showed an intermediate value. Significantly higher push-out BS values were observed for WA compared to the other groups. The MA and PA groups were statistically similar. The highest mean gap length (%) and width (MUm) were observed for PA. The groups MA and WA were statistically similar. CONCLUSION: Lower resin cement thickness resulted in better fiber post adhesion, that is, in higher bond strength and less gap formation. PMID- 24223417 TI - Adhesion is the key. PMID- 24223419 TI - Bisphenol A determination in baby bottles by chemiluminescence enzyme-linked immunosorbent assay, lateral flow immunoassay and liquid chromatography tandem mass spectrometry. AB - Two immunoassays, a Lateral Flow ImmunoAssay (LFIA) based on colloidal gold nanoparticle labels and an indirect competitive chemiluminescence enzyme-linked immunosorbent assay (CL-ELISA), were developed and a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was optimized to assess the possible release of bisphenol A (BPA, 4,4'-isopropylidenediphenol) from different plastic baby bottles treated with simulating solutions. Coating conjugate concentration, anti-BPA antibody dilution, incubation time of the primary and secondary antibodies, and tolerance to different organic solvents were optimized to obtain the best performance of the ELISA with chemiluminescent end-point detection. The influence of different buffers on LFIA performance was also evaluated. Both methods showed good repeatability (mean CV value around 13%) and sensitivity. Reproducibility tests for CL-ELISA gave a mean CV value of about 25%. The IC50 and Limit of Detection (LOD) values of CL-ELISA were 0.2 and 0.02 ng mL(-1), respectively. The LOD of LFIA was 0.1 MUg mL(-1). A LC-MS/MS method was also optimized. The separation was performed in a C18 column with a triple quadrupole mass spectrometer with electrospray ionisation interface. The method showed a good linearity in the range 2 to 500 ng mL(-1), with a regression coefficient of 0.998. In the simulating solutions the detection and quantification limits, calculated by the signal to noise level of 3 (S/N = 3), were 5.8 ng mL(-1) and 17.4 ng mL(-1), respectively. This limit of quantification was about 3 and 35 times lower than the permitted limits set by the official method CEN/TS 13130-13 (0.05 MUg mL(-1)) and by the Directive 2004/19/EC (0.6 MUg mL(-1)), respectively. The methods were applied to determine BPA release from baby bottles, performing repeated procedures according to EU and national regulations. The results demonstrated that no BPA migration from the tested plastic materials occurred with only one exception. The migrated amount, above the regulatory limits, was detected by all the mentioned assays. PMID- 24223420 TI - Stripping of acetone from water with microfabricated and membrane gas-liquid contactors. AB - Stripping of acetone from water utilizing nitrogen as a sweeping gas in co current flow was conducted in a microfabricated glass/silicon gas-liquid contactor. The chip consisted of a microchannel divided into a gas and a liquid chamber by 10 MUm diameter micropillars located next to one of the channel walls. The channel length was 35 mm, the channel width was 220 MUm and the microchannel depth 100 MUm. The micropillars were wetted by the water/acetone solution and formed a 15 MUm liquid film between them and the nearest channel wall, leaving a 195 MUm gap for gas flow. In addition, acetone stripping was performed in a microchannel membrane contactor, utilizing a hydrophobic PTFE membrane placed between two microstructured acrylic plates. Microchannels for gas and liquid flows were machined in the plates and had a depth of 850 MUm and 200 MUm respectively. In both contactors the gas/liquid interface was stabilized: in the glass/silicon contactor by the hydrophilic micropillars, while in the PTFE/acrylic one by the hydrophobic membrane. For both contactors separation efficiency was found to increase by increasing the gas/liquid flow rate ratio, but was not affected when increasing the inlet acetone concentration. Separation was more efficient in the microfabricated contactor due to the very thin liquid layer employed. PMID- 24223421 TI - Quantification of pharmaceuticals via transmission Raman spectroscopy: data sub selection. AB - We report the first systematic characterisation of data sub-selection with multivariate analysis to be applied to either TRS or the low-wavenumber Raman region. A model pharmaceutical formulation comprising two polymorphs mixed in the range of 1-99% is investigated. For data sub-selection, sparse partial least squares is for the first time applied to TRS data and compared with principal component analysis. It is found that low-wavenumber data (50-340 cm(-1)) are demonstrably superior for quantitative modelling than data in the more conventional mid-wavenumber range (340-2000 cm(-1)). Our results point the way to enhanced quantitative analytical capabilities for TRS, with potential application areas including pharmaceuticals, security and process-analytical technology, by combining data sub-selection with low-wavenumber-capable optics. PMID- 24223422 TI - Design, synthesis and characterization of a hexapeptide bio-inspired by acetylcholinesterase and its interaction with pesticide dichlorvos. AB - This paper describes the molecular modeling design, synthesis and characterization of a new bio-inspired hexapeptide of acetylcholinesterase enzyme and its interaction with the organophosphate pesticide dichlorvos monitored by UV Vis spectroscopy and mass spectrometry. This strategy can contribute to the development of synthetic receptors to be coupled to biosensor transducers, avoiding the issues associated with proteins such as low stability under different pH and temperature conditions and high production cost. The resulting data of this work indicate a strong interaction between the pesticide dichlorvos and the hexapeptide (NH3(+)-Glu-His-Gly-Gly-Pro-Ser-COO(-)) with a binding constant of 4.10 * 10(5) M(-1) and the formation of an adduct by covalent binding on the serine residue from the hexapeptide. PMID- 24223423 TI - A novel 2,6-diformyl-4-methylphenol based chemosensor for Zn(II) ions by ratiometric displacement of Cd(II) ions and its application for cell imaging on human melanoma cancer cells. AB - A new chelating ligand [4-methyl-2,6-bis-(pyridin-2-yl-hydrazonomethyl)-phenol] (1) was prepared by the condensation of 2-hydrazinylpyridine with 2,6-diformyl-p cresol. Compound 1 exhibits weak fluorescence due to intramolecular photoinduced electron transfer (PET). The sensor (1) demonstrates Zn(2+)-specific emission enhancement due to the "PET off" process through a 1:1 binding mode with the metal ion. The fluorescence quantum yield of chemosensor 1 is only 0.020, and it increases more than 14-fold (0.280) in the presence of one equivalent of the zinc ion. Interestingly, the introduction of other metal ions causes the fluorescence intensity to remain either unchanged or weakened except for Cd(2+). The new sensor showed 'naked-eye' detection of Zn(2+) ions: a color change of the solution from colorless to yellow. Ratiometric displacement of Cd(2+) ions from the complex by Zn(2+) ions supports the formation of a more stable sensor-Zn(2+) complex over the sensor-Cd(2+) complex. The experimental findings have been correlated with theoretical results using the B3LYP functional and 6-31G (d, p), LANL2DZ basis set for Cd(2+) (2) and Zn(2+) (3) complexes, respectively, by the Density Functional Theory (DFT) method. Moreover, the ability of probe 1 to sense Zn(2+) within human melanoma cancer cells has been explored, and the Zn(2+) probing process in living cells was found to be reversible with zinc chelator solution of N,N,N,N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) or EDTA. PMID- 24223424 TI - Solid phase metallurgy strategy to sub-5 nm Au-Pd and Ni-Pd bimetallic nanoparticles with controlled redox properties. AB - A solid phase metallurgy strategy is applied to synthesize Au-Pd and Ni-Pd bimetallic nanoparticles (BMNPs) with a tight sub-5 nm particle size distribution. The near-surface elemental composition and redox properties of Au Pd BMNPs can be well tailored, which leads to an optimized catalytic performance in n-hexane combustion. PMID- 24223425 TI - Oxygen release technique as a method for the determination of "delta-pO2-T" diagrams for MIEC oxides. AB - A new approach to the determination of oxygen nonstoichiometry (delta) of MIEC oxides as a continuous function of pO2 at high temperatures was developed. The description of the model allowing one to distinguish the contribution of oxygen released from the samples to the partial pressure of oxygen at the outlet of the continuous-flow fixed-bed reactor after the stepwise change of the oxygen partial pressure of inlet gas from 0.2 to 10(-5) atm and to calculate the dependence of delta on pO2 is presented. The criterion for assessing the achievement of quasi equilibrium release of oxygen from the MIEC oxides is proposed. The adequacy of the method was confirmed by comparing the obtained and published data for well studied SrCo0.8Fe0.2O3-delta and SrFeO3-delta MIEC oxides. PMID- 24223426 TI - LSPR-dependent SERS performance of silver nanoplates with highly stable and broad tunable LSPRs prepared through an improved seed-mediated strategy. AB - The application of the silver plates as a proper substrate for surface enhanced Raman spectroscopy (SERS) was performed to give deep insight on LSPR-dependent SERS performance. Firstly, an improved seed-mediated method is developed to synthesize silver nanoplates (NP) with broad-tuning localized surface plasmon resonance (LSPR) and high stability. The LSPR peaks could be tuned in the range from 485 to ~1200 nm by controlling the experimental parameters. With the treatment of sodium dodecyl sulfate (SDS), silver NPs exhibit high stability for SERS tests. The LSPR-dependent SERS study was performed by taking four typical silver NPs with LSPR peaks at 485 nm, 614 nm, 906 nm and 1130 nm as substrates. Also, two probe molecules, 4-amino-thiophenol (4-ATP) and rhodamine-6G (R-6G), were used, and both the 458 nm and 633 nm lasers were selected as excitation for the LSPR-dependent SERS study. Our results indicated that the SERS performance is largely dependent on the LSPR of the silver NP substrate at a given excitation wavelength. Specifically, the Raman signals were greatly enhanced when the laser excitation line matched (close to the LSPR band) the peak position of LSPR band. When at the excitation of 633 nm, two orders of magnitude stronger SERS signals would be observed for the Ag-614 substrate than that of the Ag-485 and Ag-1130 substrates with their LSPR peak positions far away from 633 nm. The same result can also be observed when the laser excitation at 458 nm was selected for the Ag 485 substrate. Our study gives a deep insight into LSPR-dependent SERS performance. It also gives a method for giving large SERS enhancement just by selecting a proper excitation wavelength matched to the LSPR of the substrate. PMID- 24223427 TI - Saliniquinones A-F, New Members of the Highly Cytotoxic Anthraquinone-gamma Pyrones from the Marine Actinomycete Salinispora arenicola. AB - Six new anthraquinone-gamma-pyrones, saliniquinones A-F (1-6), which are related to metabolites of the pluramycin/altromycin class, were isolated from a fermentation broth of the marine actinomycete Salinispora arenicola (strain CNS 325). Their structures were determined by analysis of one- and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data. The relative and absolute configurations of compounds 1-6 were determined by analysis of NOESY NMR spectroscopic data and by comparison of circular dichroism and optical rotation data with model compounds found in the literature. Saliniquinone A (1) exhibited potent inhibition of the human colon adenocarcinoma cell line (HCT-116) with an IC50 of 9.9 * 10-9 M. In the context of the biosynthetic diversity of S. arenicola, compounds 1-6 represent secondary metabolites that appear to be strain specific and thus occur outside of the core group of compounds commonly observed from this species. PMID- 24223428 TI - New alpha-Tetralone Galloylglucosides from the Fresh Pericarps of Juglans sigillata. AB - Three new alpha-tetralone galloylglucosides (1-3), were isolated from the fresh pericarps of Juglans sigillata (Juglandaceae), together with the six known ones. The structures of the new compounds were determined as 4,6-dihydroxy-alpha tetralone-4-O-[6'-O-(3", 4",5"-trihydroxybenzoyl)]-beta-D-glucopyranoside (1), (4S)-4,5-dihydroxy-alpha-tetralone-4-O-[6'-O-(3",4",5"-trihydroxybenzoyl)]-beta-D glucopyranoside (2) and (4S)-4,5,6-tri-hydroxy-alpha-tetralone-4-O-[6'-O (3",4",5"-trihydroxybenzoyl)]-beta-D-glucopyranoside (3), respectively, on the basis of detailed spectroscopic analyses, and acidic and enzymatic hydrolysis. The antimicrobial activities of the isolated compounds (2, 4 and 7-9) were evaluated. PMID- 24223429 TI - Household Migration, Remittances, and Its Impact on Health in Indonesia. AB - The growing flow of migrant's remittances has generated much interest in understanding the socioeconomic consequences of household migration for individuals and families in migrant-sending areas. This paper examines the effect of household migration on health status, as measured by nutritional status, of adults who remained behind in rural Indonesia, a setting with high rate of out migration and poor nutritional profiles. Assuming that remittances may improve household economic resources and thus change dietary intake and health-related investment, household migration may be associated with both the risks of undernutrition and overnutrition. The analyses use longitudinal data from the Indonesian Family Life Survey and fixed-effect regressions. The results show that adults in emigrant household were significantly less susceptible to being underweight than those in non-migrant households, but they did not have increased risk of being overweight. The improved nutritional status was restricted to people in households with labor migrants, highlighting the role of remittances in improving nutritional intake. The health gain also was concentrated among women, increased with the number of out-migrants, and was revealed over time as remittances arrived. Overall, this study demonstrates the beneficial role of household migration, especially the resulting remittances, in the health status of household members in resource-constrained settings. Improving transfers of remittances would be helpful in reducing the problem of undernutrition in poor migrant-sending areas. PMID- 24223430 TI - Sustainable forest management in a time of ecosystem services frameworks: common ground and consequences. PMID- 24223431 TI - Towards a systems approach for understanding honeybee decline: a stocktaking and synthesis of existing models. AB - The health of managed and wild honeybee colonies appears to have declined substantially in Europe and the United States over the last decade. Sustainability of honeybee colonies is important not only for honey production, but also for pollination of crops and wild plants alongside other insect pollinators. A combination of causal factors, including parasites, pathogens, land use changes and pesticide usage, are cited as responsible for the increased colony mortality.However, despite detailed knowledge of the behaviour of honeybees and their colonies, there are no suitable tools to explore the resilience mechanisms of this complex system under stress. Empirically testing all combinations of stressors in a systematic fashion is not feasible. We therefore suggest a cross-level systems approach, based on mechanistic modelling, to investigate the impacts of (and interactions between) colony and land management.We review existing honeybee models that are relevant to examining the effects of different stressors on colony growth and survival. Most of these models describe honeybee colony dynamics, foraging behaviour or honeybee - varroa mite - virus interactions.We found that many, but not all, processes within honeybee colonies, epidemiology and foraging are well understood and described in the models, but there is no model that couples in-hive dynamics and pathology with foraging dynamics in realistic landscapes.Synthesis and applications. We describe how a new integrated model could be built to simulate multifactorial impacts on the honeybee colony system, using building blocks from the reviewed models. The development of such a tool would not only highlight empirical research priorities but also provide an important forecasting tool for policy makers and beekeepers, and we list examples of relevant applications to bee disease and landscape management decisions. PMID- 24223432 TI - Motion cues that make an impression: Predicting perceived personality by minimal motion information. AB - The current study presents a methodology to analyze first impressions on the basis of minimal motion information. In order to test the applicability of the approach brief silent video clips of 40 speakers were presented to independent observers (i.e., did not know speakers) who rated them on measures of the Big Five personality traits. The body movements of the speakers were then captured by placing landmarks on the speakers' forehead, one shoulder and the hands. Analysis revealed that observers ascribe extraversion to variations in the speakers' overall activity, emotional stability to the movements' relative velocity, and variation in motion direction to openness. Although ratings of openness and conscientiousness were related to biographical data of the speakers (i.e., measures of career progress), measures of body motion failed to provide similar results. In conclusion, analysis of motion behavior might be done on the basis of a small set of landmarks that seem to capture important parts of relevant nonverbal information. PMID- 24223433 TI - Early Adult Obesity and U.S. Women's Lifetime Childbearing Experiences. AB - Literature from multiple disciplines suggests that women who are obese during early adulthood may accumulate social and physiological impediments to childbearing across their reproductive lives. This led the authors to investigate whether obese young women have different lifetime childbearing experiences than leaner peers by analyzing data from 1,658 female participants in the 1979 National Longitudinal Survey of Youth. Study sample members were nulliparous women ages 20 - 25 in 1982. The authors examined their childbearing experiences between 1982 and 2006 and found that young women who were obese at baseline had higher odds of remaining childless and increased odds of underachieving fertility intentions than young women who were normal weight at baseline. These results suggest that obesity has long-term ramifications for women's childbearing experiences, with respect to whether and how many children women have in general and relative to the number of children they want. PMID- 24223435 TI - Fully Bayesian hierarchical modelling in two stages, with application to meta analysis. AB - Meta-analysis is often undertaken in two stages, with each study analysed separately in stage 1 and estimates combined across studies in stage 2. The study specific estimates are assumed to arise from normal distributions with known variances equal to their corresponding estimates. In contrast, a one-stage analysis estimates all parameters simultaneously. A Bayesian one-stage approach offers additional advantages, such as the acknowledgement of uncertainty in all parameters and greater flexibility. However, there are situations when a two stage strategy is compelling, e.g. when study-specific analyses are complex and/or time consuming. We present a novel method for fitting the full Bayesian model in two stages, hence benefiting from its advantages while retaining the convenience and flexibility of a two-stage approach. Using Markov chain Monte Carlo methods, posteriors for the parameters of interest are derived separately for each study. These are then used as proposal distributions in a computationally efficient second stage. We illustrate these ideas on a small binomial data set; we also analyse motivating data on the growth and rupture of abdominal aortic aneurysms. The two-stage Bayesian approach closely reproduces a one-stage analysis when it can be undertaken, but can also be easily carried out when a one-stage approach is difficult or impossible. PMID- 24223436 TI - A coupled hidden Markov model for disease interactions. AB - To investigate interactions between parasite species in a host, a population of field voles was studied longitudinally, with presence or absence of six different parasites measured repeatedly. Although trapping sessions were regular, a different set of voles was caught at each session, leading to incomplete profiles for all subjects. We use a discrete time hidden Markov model for each disease with transition probabilities dependent on covariates via a set of logistic regressions. For each disease the hidden states for each of the other diseases at a given time point form part of the covariate set for the Markov transition probabilities from that time point. This allows us to gauge the influence of each parasite species on the transition probabilities for each of the other parasite species. Inference is performed via a Gibbs sampler, which cycles through each of the diseases, first using an adaptive Metropolis-Hastings step to sample from the conditional posterior of the covariate parameters for that particular disease given the hidden states for all other diseases and then sampling from the hidden states for that disease given the parameters. We find evidence for interactions between several pairs of parasites and of an acquired immune response for two of the parasites. PMID- 24223437 TI - Dreams Fulfilled and Shattered: Determinants of Segmented Assimilation in the Second Generation. AB - We summarize prior theories on the adaptation process of the contemporary immigrant second generation as a prelude to presenting additive and interactive models showing the impact of family variables, school contexts and academic outcomes on the process. For this purpose, we regress indicators of educational and occupational achievement in early adulthood on predictors measured three and six years earlier. The Children of Immigrants Longitudinal Study (CILS), used for the analysis, allows us to establish a clear temporal order among exogenous predictors and the two dependent variables. We also construct a Downward Assimilation Index (DAI), based on six indicators and regress it on the same set of predictors. Results confirm a pattern of segmented assimilation in the second generation, with a significant proportion of the sample experiencing downward assimilation. Predictors of the latter are the obverse of those of educational and occupational achievement. Significant interaction effects emerge between these predictors and early school contexts, defined by different class and racial compositions. Implications of these results for theory and policy are examined. PMID- 24223434 TI - RECENT SYNTHETIC DEVELOPMENTS AND APPLICATIONS OF THE ULLMANN REACTION. A REVIEW. PMID- 24223438 TI - Structuring the Future: Anticipated Life Events, Peer Networks, and Adolescent Sexual Behavior. AB - While prior research has established associations between individual expectations of future events and risk behavior among adolescents, the potential effects of peers' future perceptions on risk-taking have been overlooked. We extend prior research by testing whether peers' anticipation of college completion is associated with adolescent sexual risk-taking. We also examine whether adolescents' perceptions of the negative consequences of pregnancy and idealized romantic relationship scripts mediate the association between peers' anticipation of college completion and sexual risk-taking. Results from multivariate regression models with data from the National Longitudinal Study of Adolescent Health (Add Health) indicate peers' anticipation of college completion is negatively associated with a composite measure of sexual risk-taking and positively associated with the odds of abstaining from sexual intercourse and only engaging in intercourse with a romantic partner (compared to having intercourse with a non-romantic partner). In addition, perceptions of the negative consequences of pregnancy and sexualized relationship scripts appear to mediate a large portion of the association between peers' anticipation of future success and sexual risk-taking and the likelihood of abstaining (but not engaging in romantic-only intercourse). Results from our study underscore the importance of peers in shaping adolescent sexual behavior. PMID- 24223439 TI - 'Recovery work' and 'magic' among long-term mental health service-users. AB - Based on an extended period of qualitative research with mental health service users in north-east England, this article considers the various forms of 'magical work' and 'recovery work' that emerge in the lives of people living with severe mental health problems. Given the now sizeable body of literature which seeks to problematize traditional conceptual boundaries of work, the article asks to what extent these hidden and unusual work-forms might also be considered legitimate members of the category. Rather than argue for the expansion of the construct to accommodate these activities, the paper attempts simply to problematize the extent to which so-called 'mad' forms of work are irresolvably different to more conventional forms of occupation. In challenging notions of the psychiatric patient as inevitably inactive, new vocabularies for service-user work are explored. Concluding remarks are also directed to recent policy debates concerning 'back-to-work' welfare reform for long-term out of work service-users. PMID- 24223441 TI - PLACE OF ORIGIN AND LABOR MARKET OUTCOMES AMONG MIGRANT WORKERS IN URBAN CHINA. AB - The localistic enclave is a special kind of enclave in urban China, which is characterized by high concentration of rural migrants from the same place of origin. Prior research has documented that rural migrants work in these localistic enclaves, but the significance of participation in them for labor market outcomes among migrant workers has yet to be determined. In this article, we argue that localistic economic enclaves may improve the labor force outcomes of rural-to-urban migrants. We report results from a study of the social determinants and consequences of working in localistic enclaves, based on data from a 2010 survey of migrant workers in the Pearl River and the Yangzi River Deltas. The results provide limited support for our hypothesis: Localistic enclaves enable migrant workers to earn higher earnings overall, but the earnings returns to human capital in an enclave are limited. PMID- 24223440 TI - Total Syntheses of Proposed (+/-)-Trichodermatides B and C. AB - Total syntheses of putative (+/-)-trichodermatides B and C are described. These efficient syntheses feature the oxa-[3 + 3] annulation strategy, leading to B and C along with their respective C2-epimers. However, these synthetic samples are spectroscopically very different from the natural products. DFT calculations of C13 chemical shifts are conducted and the predicted values are in good agreement with those of synthetic samples, thereby questioning in the accuracy of structural assignments of trichodermatides B and C. PMID- 24223442 TI - Estimating snow water equivalent from GPS vertical site-position observations in the western United States. AB - [1] Accurate estimation of the characteristics of the winter snowpack is crucial for prediction of available water supply, flooding, and climate feedbacks. Remote sensing of snow has been most successful for quantifying the spatial extent of the snowpack, although satellite estimation of snow water equivalent (SWE), fractional snow covered area, and snow depth is improving. Here we show that GPS observations of vertical land surface loading reveal seasonal responses of the land surface to the total weight of snow, providing information about the stored SWE. We demonstrate that the seasonal signal in Scripps Orbit and Permanent Array Center (SOPAC) GPS vertical land surface position time series at six locations in the western United States is driven by elastic loading of the crust by the snowpack. GPS observations of land surface deformation are then used to predict the water load as a function of time at each location of interest and compared for validation to nearby Snowpack Telemetry observations of SWE. Estimates of soil moisture are included in the analysis and result in considerable improvement in the prediction of SWE. Citation: Ouellette, K. J., C. de Linage, and J. S. Famiglietti (2013), Estimating snow water equivalent from GPS vertical site position observations in the western United States, Water Resour. Res., 49, 2508 2518, doi:10.1002/wrcr.20173. PMID- 24223443 TI - Performance of complex snow cover descriptions in a distributed hydrological model system: A case study for the high Alpine terrain of the Berchtesgaden Alps. AB - [1] Runoff generation in Alpine regions is typically affected by snow processes. Snow accumulation, storage, redistribution, and ablation control the availability of water. In this study, several robust parameterizations describing snow processes in Alpine environments were implemented in a fully distributed, physically based hydrological model. Snow cover development is simulated using different methods from a simple temperature index approach, followed by an energy balance scheme, to additionally accounting for gravitational and wind-driven lateral snow redistribution. Test site for the study is the Berchtesgaden National Park (Bavarian Alps, Germany) which is characterized by extreme topography and climate conditions. The performance of the model system in reproducing snow cover dynamics and resulting discharge generation is analyzed and validated via measurements of snow water equivalent and snow depth, satellite based remote sensing data, and runoff gauge data. Model efficiency (the Nash Sutcliffe coefficient) for simulated runoff increases from 0.57 to 0.68 in a high Alpine headwater catchment and from 0.62 to 0.64 in total with increasing snow model complexity. In particular, the results show that the introduction of the energy balance scheme reproduces daily fluctuations in the snowmelt rates that trace down to the channel stream. These daily cycles measured in snowmelt and resulting runoff rates could not be reproduced by using the temperature index approach. In addition, accounting for lateral snow transport changes the seasonal distribution of modeled snowmelt amounts, which leads to a higher accuracy in modeling runoff characteristics. PMID- 24223444 TI - Insights into non-Fickian solute transport in carbonates. AB - [1] We study and explain the origin of early breakthrough and long tailing plume behavior by simulating solute transport through 3-D X-ray images of six different carbonate rock samples, representing geological media with a high degree of pore scale complexity. A Stokes solver is employed to compute the flow field, and the particles are then transported along streamlines to represent advection, while the random walk method is used to model diffusion. We compute the propagators (concentration versus displacement) for a range of Peclet numbers (Pe) and relate it to the velocity distribution obtained directly on the images. There is a very wide distribution of velocity that quantifies the impact of pore structure on transport. In samples with a relatively narrow spread of velocities, transport is characterized by a small immobile concentration peak, representing essentially stagnant portions of the pore space, and a dominant secondary peak of mobile solute moving at approximately the average flow speed. On the other hand, in carbonates with a wider velocity distribution, there is a significant immobile peak concentration and an elongated tail of moving fluid. An increase in Pe, decreasing the relative impact of diffusion, leads to the faster formation of secondary mobile peak(s). This behavior indicates highly anomalous transport. The implications for modeling field-scale transport are discussed. Citation: Bijeljic, B., P. Mostaghimi, and M. J. Blunt (2013), Insights into non-Fickian solute transport in carbonates, Water Resour. Res., 49, 2714-2728, doi:10.1002/wrcr.20238. PMID- 24223445 TI - Modified Immersed Finite Element Method For Fully-Coupled Fluid-Structure Interations. AB - In this paper, we develop a "modified" immersed finite element method (mIFEM), a non-boundary-fitted numerical technique, to study fluid-structure interactions. Using this method, we can more precisely capture the solid dynamics by solving the solid governing equation instead of imposing it based on the fluid velocity field as in the original immersed finite element (IFEM). Using the IFEM may lead to severe solid mesh distortion because the solid deformation is been over estimated, especially for high Reynolds number flows. In the mIFEM, the solid dynamics is solved using appropriate boundary conditions generated from the surrounding fluid, therefore produces more accurate and realistic coupled solutions. We show several 2-D and 3-D testing cases where the mIFEM has a noticeable advantage in handling complicated fluid-structure interactions when the solid behavior dominates the fluid flow. PMID- 24223446 TI - Psychopathic Personality and Negative Parent-to-Child Affect: A Longitudinal Cross-lag Twin Study. AB - PURPOSE: Previous studies that have explored the relationship between parenting style and children's antisocial behavior have generally found significant bidirectional effects, whereby parenting behaviors influence their child's antisocial outcomes, but a child's behaviors also lead to changes in parenting style. METHODS: The present study investigated the genetic and environmental underpinnings of the longitudinal relationship between negative parent-to-child affect and psychopathic personality in a sample of 1,562 twins. Using a biometrical cross-lag analysis, bidirectional effects were investigated across two waves of assessment when the twins were ages 9-10 and 14-15, utilizing both caregiver and youth self-reports. RESULTS: Results demonstrated that negative parental affects observed at ages 9-10 influenced the child's later psychopathic personality at ages 14-15, based on both caregiver and youth self-reports. For these 'parent-driven effects', both genetic and non-shared environmental factors were important in the development of later psychopathic personality during adolescence. There were additional 'child-driven effects' such that children's psychopathic personality at ages 9-10 influenced negative parent-to-child affect at ages 14-15, but only within caregiver reports. CONCLUSIONS: Thus, children's genetically influenced psychopathic personality seemed to evoke parental negativity at ages 14-15, highlighting the importance of investigating bidirectional effects in parent-child relationships to understand the development of these traits. PMID- 24223447 TI - Multiple Imputation For Combined-Survey Estimation With Incomplete Regressors In One But Not Both Surveys. AB - Within-survey multiple imputation (MI) methods are adapted to pooled-survey regression estimation where one survey has more regressors, but typically fewer observations, than the other. This adaptation is achieved through: (1) larger numbers of imputations to compensate for the higher fraction of missing values; (2) model-fit statistics to check the assumption that the two surveys sample from a common universe; and (3) specificying the analysis model completely from variables present in the survey with the larger set of regressors, thereby excluding variables never jointly observed. In contrast to the typical within survey MI context, cross-survey missingness is monotonic and easily satisfies the Missing At Random (MAR) assumption needed for unbiased MI. Large efficiency gains and substantial reduction in omitted variable bias are demonstrated in an application to sociodemographic differences in the risk of child obesity estimated from two nationally-representative cohort surveys. PMID- 24223448 TI - Identifying Early Childhood Personality Dimensions Using the California Child Q Set and Prospective Associations With Behavioral and Psychosocial Development. AB - The present study used an empirical, "bottom-up" approach to delineate the structure of the California Child Q-Set (CCQ), a comprehensive set of personality descriptors, in a sample of 373 preschool-aged children. This approach yielded two broad trait dimensions, Adaptive Socialization (emotional stability, compliance, intelligence) and Anxious Inhibition (emotional/behavioral introversion). Results demonstrate the value of using empirical derivation to investigate the structure of personality in young children, speak to the importance of early-evident personality traits for adaptive development, and are consistent with a growing body of evidence indicating that personality structure in young children is similar, but not identical to, that in adults, suggesting a model of broad personality dimensions in childhood that evolve into narrower traits in adulthood. PMID- 24223449 TI - The ADHD debate: being mindful of complexity and wary of reductionist explanations and polarization: Commentary on 'A social relational critique of the biomedical definition and treatment of ADHD; ethical, practical and political implications' PMID- 24223450 TI - A composite likelihood approach for spatially correlated survival data. AB - The aim of this paper is to provide a composite likelihood approach to handle spatially correlated survival data using pairwise joint distributions. With e commerce data, a recent question of interest in marketing research has been to describe spatially clustered purchasing behavior and to assess whether geographic distance is the appropriate metric to describe purchasing dependence. We present a model for the dependence structure of time-to-event data subject to spatial dependence to characterize purchasing behavior from the motivating example from e commerce data. We assume the Farlie-Gumbel-Morgenstern (FGM) distribution and then model the dependence parameter as a function of geographic and demographic pairwise distances. For estimation of the dependence parameters, we present pairwise composite likelihood equations. We prove that the resulting estimators exhibit key properties of consistency and asymptotic normality under certain regularity conditions in the increasing-domain framework of spatial asymptotic theory. PMID- 24223451 TI - The Value of Workshops on Psychological Flexibility for Early Childhood Special Education Staff. AB - High stress and burnout are common for early childhood special educators, contributing to high rates of attrition, diminished educational effectiveness, and high turnover. Acceptance and Commitment Therapy (ACT) is a promising approach for the prevention and treatment of a wide variety of problems. Using a randomized wait-list control design, this pilot study evaluated whether ACT workshops delivered to preschool teachers who serve children with developmental disabilities would improve stress-related problems of teachers (i.e., stress, depression, and burnout) and increase collegial support. At pretest, measures of experiential avoidance (EA) and mindful awareness (MA) showed significant relationships to reports of depression, stress, and burnout. The intervention reduced staff members' EA, increased teachers' MA and valued living (VL), and improved teachers' sense of efficacy. This suggests that ACT workshops can help influence factors affecting depression, stress, and burnout in an early childhood special education setting. PMID- 24223452 TI - New heme-dioxygen and carbon monoxide adducts using pyridyl or imidazolyl tailed porphyrins. AB - Inspired by the chemistry relevant to dioxygen storage, transport and activation by metalloproteins, in particular for heme/copper oxidases, and carbon monoxide binding to metal-containing active sites as a probe or surrogate for dioxygen binding, a series of heme derived dioxygen and CO complexes have been designed, synthesized, and characterized with respect to their physical properties and reactivity. The focus of this study is in the description and comparison of three types heme-superoxo and heme-CO adducts. The starting point is in the characterization of the reduced heme complexes, [(F8)FeII], [(PPy)FeII] and [(PIm)FeII], where F8, PPy and PIm are iron(II)-porphyrinates and where PPy and PIm possess a covalently tethered axial base pyridyl or imidazolyl group, respectively. The spin-state properties of these complexes vary with solvent. The low temperature reaction between O2 and these reduced porphyrin FeII complex yield distinctive low spin heme-superoxo adducts. The dioxygen binding properties for all three complexes are shown to be reversible, via alternate argon or O2 bubbling. Carbon monoxide binds to the reduced heme-FeII precursors to form low spin heme-CO adducts. The implications for future investigations of these heme O2 and CO adducts are discussed. PMID- 24223454 TI - Diagnostic significance of serum eotaxin-1 level in gastric cancer patients. AB - INTRODUCTION: Gastric cancer is the second cause of cancer-related deaths worldwide. Delayed diagnosis leads to high mortality rates. Eotaxin-1 was originally discovered as an eosinophil-selective chemoattractant and may play a role in a number of chronic inflammatory diseases, cancer, and other gastrointestinal disorders. The aim of this study was to analyse diagnostic and prognostic significance of serum eotaxin-1 (s-eotaxin-1) levels in gastric cancer. METHODS: Sixty gastric cancer patients and 69 healthy subjects were included into the study. S-eotaxin-1 levels were compared with clinicopathological features and outcomes in gastric cancer. RESULTS: Serum levels of eotaxin-1 in gastric cancer patients were significantly higher than controls (74.51 +/- 16.65 pg/mL versus 16.79 +/- 5.52 pg/mL, respectively (P < 0.001)). The s-eotaxin-1 levels did not differ significantly with histopathological grade, tumor-node-metastasis (TNM) stage, tumor localization, lymph node metastases, positive lymph node ratio, size, perineural and perivascular invasion. So there is no relationship found between s-eotaxin-1 level and prognosis. CONCLUSION: S-eotaxin-1 levels may be used as an easily available biomarker for gastric cancer risk and may alert physicians for early diagnosis. Due to the limited number of patients included in this study, larger cohort studies are warranted to validate the diagnostic value of s-eotaxin-1 level in gastric cancer. PMID- 24223453 TI - Polymorphisms of the homologous recombination gene RAD51 in keratoconus and Fuchs endothelial corneal dystrophy. AB - PURPOSE: We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320) and c.-98G>C (rs 1801321) polymorphisms of the RAD51 gene and the occurrence of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) in dependence on some environmental factors. METHODS: The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP. RESULTS: The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75-5.13). On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31-0.88). We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28-0.92; crude OR 0.53, 95% CI 0.30-0.92, resp.), while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01-3.36; crude OR 1.90, 95% CI 1.09-3.29, resp.). CONCLUSIONS: The c.-61T/T and c.-98G>C polymorphisms of the RAD51 gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases. PMID- 24223455 TI - Increased LEF1 expression and decreased Notch2 expression are strong predictors of poor outcomes in colorectal cancer patients. AB - BACKGROUND/OBJECTIVE: We aimed to examine the expression of lymphoid enhancer factor 1 (LEF1) and Notch2 in colorectal cancer (CRC) and their association with clinicopathologic variables and CRC patients' prognosis. METHODS: Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to assess the expression of LEF1 and Notch2 in 184 patients with CRC. RESULTS: We observed a strong negative correlation between LEF1 expression and Notch2 expression (P < 0.001). Both LEF1 mRNA and protein expression increased while the Notch2 mRNA and protein expression decreased in tumor specimens compared with the matched paratumorous normal tissue (P < 0.001). An increase in LEF1 protein expression was significantly associated with lymph node metastases, distant metastasis, advanced TNM (tumor-node-metastasis) stage, and shorter overall survival. A decrease in Notch2 protein expression was associated with poorly differentiated tumors, lymph node metastases, distant metastasis, advanced TNM stage, and shorter overall survival of patients. In the multivariate Cox regression analysis, the LEF1 protein expression (P < 0.001), Notch2 protein expression (P < 0.001), TNM stage (P < 0.001), and the combination of increased LEF1 protein coexpression and decreased Notch2 protein coexpression (P < 0.001) were found to be independent prognostic indicators in CRC. CONCLUSION: Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients. PMID- 24223456 TI - Asymmetric and symmetric dimethylarginine in adolescents with hyperuricemia. AB - The purpose of this work was to investigate if in adolescents with hyperuricemia serum levels of asymmetric and symmetric dimethylarginine (ADMA, SDMA) are increased and if their levels correlate with serum uric acid (UA). PATIENTS AND METHODS: The study group consisted of 58 hyperuricemic patients aged median 16.15 Q1-Q3 (14-17). The reference group contained 27 healthy individuals with normal serum UA level. ADMA and SDMA were measured by immunoenzymatic ELISA commercial kits and expressed in MU mol/L. Serum UA was measured by the colorimetric method. RESULTS: In hyperuricemic patients serum ADMA values did not differ between two estimated groups (P > 0.05); however, SDMA was significantly higher than in reference group (P < 0.01). Serum ADMA and SDMA correlated positively with UA (r = 0.34, P < 0.01) (r = 0.31, P < 0.01) and hs-CRP (r = 0.20, P < 0.05) (r = 0.36, P < 0.01), respectively. CONCLUSION: We demonstrated increased SDMA but not ADMA levels in adolescents with hyperuricemia and their correlation with serum uric acid levels. However, at the moment it is difficult to answer the question if it is just coexistence of these factors or any mechanism linking uric acid and methylated arginines really exists. PMID- 24223457 TI - Early time-dependent dynamic changes of TBET and GATA3 mRNA expressions in patients with acute coronary syndrome. AB - BACKGROUND: T-box expressed in T cells (TBET) and guanine adenine thymine adenine sequence-binding protein 3 (GATA3) play important roles in the differentiation of Th1 and Th2 subsets, which contributes to the progression of acute coronary syndrome (ACS). OBJECTIVE: This study aimed to investigate the temporal change of TBET/GATA3 mRNA ratio in ACS. METHODS: Thirty-three patients suspected of ACS with symptom onset within 24 hours were recruited. Blood samples were taken after arrival at the emergency department and at hourly intervals until the 6th hour. The mRNA expressions of TBET and GATA3 were quantified by a real-time RT-qPCR. RESULTS: The TBET/GATA3 mRNA ratio was elevated dramatically in patients with acute myocardial infarction (AMI) and exhibited biphasic M-shaped release kinetics with two distinct peaks. The ratio was elevated 2 hours after symptom onset, dropped to the lowest level at 10 hours, and rose to the second peak at 14 hours. A similar biphasic M-shaped curve was observed in AMI patients with blood samples taken prior to any intervention. CONCLUSIONS: The TBET/GATA3 mRNA ratio was elevated in AMI patients throughout most of the first 20 hours after symptom onset. The biphasic M-shaped release kinetics was more likely to reflect pathophysiological changes rather than treatment effects. PMID- 24223458 TI - Impact of IL12B gene rs 3212227 polymorphism on fibrosis, liver inflammation, and response to treatment in genotype 4 Egyptian hepatitis C patients. AB - INTRODUCTION: Hepatitis C virus (HCV) infection affects almost 3% of the world's population with the highest prevalence in Egypt (15%). The standard therapy; pegylated interferon (PEG-IFN) and ribavirin, is effective in only 60% of Egyptian patients; moreover it is costly, prolonged, and has severe side effects, so prediction of response is essential to reduce burden of unfavorable treatment. Several viral and host factors have been proved to affect response to the treatment PEG-IFN and ribavirin; the strongest of them is polymorphisms near IL28B; nonetheless, nonresponse in patients with favorable IL28B is still unexplained, which implies the importance of studying other immunological factors that may correlate with response. Interleukin 12 (IL-12) is one of the most important proinflammatory cytokine presented with the initiation of immune response, determining Th1 and Th2 differentiation. A functional single nucleotide polymorphism (A/C) at the 3' untranslated region (3'UTR) at position 1188 (NCBI SNP database no 3212227) was reported to be associated with responding more efficiently to antiviral combination therapy in HCV genotype 1 infected patients. The present study aims to evaluate association between this polymorphism with fibrosis stages, necroinflammation activity, response to the combined therapy, and gender in Egyptian HCV genotype 4. MATERIAL AND METHODS: A total of 133 Egyptian chronic HCV (CHCV) patients were treated with IFN/RBV and were followed up. IL12B 1188 A/C genotyping was performed using polymerase chain reaction restriction fragment length polymorphism (PRC-RFLP) analysis. RESULTS: A nonsignificant trend for higher sustained virological response (SVR) was observed in patients homozygote for IL12B 1188 A/C SNP CC genotype (69% SVR versus 30.8% NR) only but not in AC and AA genotypes. No association was detected between IL12B 1188 A/C polymorphism and less severe fibrosis or less liver activity. By stratification of response according to gender genotype, a significant difference in response between males and females was seen among AA genotype carriers only due to high number of non responder females. CONCLUSION: IL12B CC genotype appears to have some influence on SVR achievement but not on severe fibrosis and severe necroinflamation activity. Females carrying A/A genotype of IL12B 1188 A/C SNP achieve less SVR than those carrying AC and CC genotypes. PMID- 24223459 TI - The MTHFR 677T allele may influence the severity and biochemical risk factors of Alzheimer's disease in an Egyptian population. AB - OBJECTIVE: We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt. METHODS: Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed. RESULTS: No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels. CONCLUSIONS: The MTHFR 677C>T polymorphism- especially the presence of one copy of the T allele--appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker. PMID- 24223460 TI - Role of immunomarkers in the clinicopathological analysis of unicystic ameloblastoma. AB - PURPOSE: The clinical behavior of unicystic ameloblastoma varies according to its subtype. The assessment of its proliferative capacity, neovascularization, and invasiveness using relevant immunomarkers may aid in appropriate surgical therapeutic protocol. METHODS: 18 cases of clinically and histologically confirmed unicystic ameloblastoma, categorized as luminal, intraluminal, or mural subtypes, were analyzed retrospectively. Immunomarkers such as Ki-67, CD34, MMP 2, and MMP-9 were studied to evaluate their behavior. RESULTS: Labeling index of Ki-67 was 4.25% in the intraluminal subtype, compared with 2.14% in the luminal and 4.04% in the mural variant (P = 0.3). CD34 immunostaining was significantly higher in the mural variant (43 per high power field) than the other two subtypes (P = 0.04). MMP-2 and MMP-9 were strongly expressed in mural, moderately in intraluminal, and weakly to absent in luminal variant. CONCLUSIONS: High proliferative index, angiogenesis, and protease activity in the mural ameloblastoma, ascertained by the expression of these markers, confirm its aggressive phenotype. The intraluminal and luminal subtype exhibiting decreased expression are compatible with their indolent clinical behavior. PMID- 24223461 TI - Expression and clinical significance of livin protein in hepatocellular carcinoma. AB - In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC. PMID- 24223462 TI - Procalcitonin levels in patients with complete and incomplete Kawasaki disease. AB - Incomplete Kawasaki disease (iKD) is considered to be a less complete form of Kawasaki disease (cKD), and several differences in the laboratory presentations of iKD and cKD have been noted. We investigated serum procalcitonin levels in patients with iKD, cKD, and other febrile diseases (a control group). Seventy seven patients with cKD, 24 with iKD, and 41 controls admitted to our hospital from November 2009 to November 2011 were enrolled in the present study. We obtained four measurements of serum procalcitonin levels and those of other inflammatory markers from each patient. Samples were taken for analysis on the day of diagnosis (thus before treatment commenced; D0) and 2 (D2), 14 (D14), and 56 days (D56) after intravenous immunoglobulin infusion. We obtained control group data at D0. The mean D0 serum procalcitonin levels of cKD patients (0.71 +/ 1.36 ng/mL) and controls (0.67 +/- 1.06 ng/mL) were significantly higher than those of iKD patients (0.26 +/- 0.26 ng/mL) (P = 0.014 and P = 0.041, resp.). No significant difference in mean procalcitonin level was evident among groups at any subsequent time. In conclusion, the serum procalcitonin level of patients with acute-stage cKD was significantly higher than that of iKD patients. PMID- 24223464 TI - Hypovitaminosis D in geriatric acute care unit: a biomarker of longer length of stay. AB - BACKGROUND: Hypovitaminosis D is linked to unstable health in older adults. Our objectives were to determine (i) the difference in length of stay (LOS) in geriatric acute care unit between inpatients with and without hypovitaminosis D and (ii) whether there was a linear association between serum 25-hydroxyvitamin D (25OHD) concentration and LOS. METHODS: 253 inpatients admitted in 2008 to the geriatric acute care unit of Angers University Hospital, France, (mean age+/ standard deviation, 86.2 +/- 6.0 years; 66.8% female) were included in this historical cohort study. LOS was calculated by subtracting day of admission from day of discharge. Hypovitaminosis D was defined as 25OHD<=50 nmol/L at the time of admission. Age, gender, place of life, functional independence, reason for admission, number of acute diseases and comorbidities, use of vitamin D supplements, and creatinine clearance were used as confounders. RESULTS: Participants with hypovitaminosis D had longer LOS than their counterparts (15.2 +/- 8.2 days versus 12.1 +/- 7.0 days, P = 0.017), underlining a mean difference of 3 days. 25OHD concentration inversely correlated (r = -0.14, P = 0.028) and was inversely associated with LOS (adjusted beta = -0.07 [95%CI: -0.14; -0.02], P = 0.043). CONCLUSIONS: We found an inverse linear association between serum 25OHD concentrations and LOS in a geriatric acute care unit. Participants with 25OHD>50 nmol/L were hospitalized on average 3 days less than those with 25OHD<=50 nmol/L. PMID- 24223463 TI - A semiautomated framework for integrating expert knowledge into disease marker identification. AB - BACKGROUND: The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. OBJECTIVE: To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. METHODS: The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC). Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. RESULTS: The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. CONCLUSIONS: Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification. PMID- 24223465 TI - Reconstruction of Calmodulin Single-Molecule FRET States, Dye-Interactions, and CaMKII Peptide Binding by MultiNest and Classic Maximum Entropy. AB - We analyze single molecule FRET burst measurements using Bayesian nested sampling. The MultiNest algorithm produces accurate FRET efficiency distributions from single-molecule data. FRET efficiency distributions recovered by MultiNest and classic maximum entropy are compared for simulated data and for calmodulin labeled at residues 44 and 117. MultiNest compares favorably with maximum entropy analysis for simulated data, judged by the Bayesian evidence. FRET efficiency distributions recovered for calmodulin labeled with two different FRET dye pairs depended on the dye pair and changed upon Ca2+ binding. We also looked at the FRET efficiency distributions of calmodulin bound to the calcium/calmodulin dependent protein kinase II (CaMKII) binding domain. For both dye pairs, the FRET efficiency distribution collapsed to a single peak in the case of calmodulin bound to the CaMKII peptide. These measurements strongly suggest that consideration of dye-protein interactions is crucial in forming an accurate picture of protein conformations from FRET data. PMID- 24223466 TI - Mercury capture by native fly ash carbons in coal-fired power plants. AB - The control of mercury in the air emissions from coal-fired power plants is an on going challenge. The native unburned carbons in fly ash can capture varying amounts of Hg depending upon the temperature and composition of the flue gas at the air pollution control device, with Hg capture increasing with a decrease in temperature; the amount of carbon in the fly ash, with Hg capture increasing with an increase in carbon; and the form of the carbon and the consequent surface area of the carbon, with Hg capture increasing with an increase in surface area. The latter is influenced by the rank of the feed coal, with carbons derived from the combustion of low-rank coals having a greater surface area than carbons from bituminous- and anthracite-rank coals. The chemistry of the feed coal and the resulting composition of the flue gas enhances Hg capture by fly ash carbons. This is particularly evident in the correlation of feed coal Cl content to Hg oxidation to HgCl2, enhancing Hg capture. Acid gases, including HCl and H2SO4 and the combination of HCl and NO2, in the flue gas can enhance the oxidation of Hg. In this presentation, we discuss the transport of Hg through the boiler and pollution control systems, the mechanisms of Hg oxidation, and the parameters controlling Hg capture by coal-derived fly ash carbons. PMID- 24223467 TI - Health Risk Behavior and Sexual Assault Among Ethnically Diverse Women. AB - Sexual assault is associated with a number of health risk behaviors in women. It has been hypothesized that these risk behaviors, such as hazardous drinking, may represent women's attempts to cope with psychological distress, such as symptoms of depression and anxiety. However, extant research has failed to evaluate these relationships among ethnic minority samples or identify the mechanisms responsible for this association. The current study examined sexual assault history and two health risk behaviors (hazardous drinking and engaging in sexual behavior to regulate negative affect) in a diverse sample of 1,620 college women. Depression and anxiety were examined as mediators of the relationship between sexual assault and health risk behaviors. There was evidence of moderated mediation, such that for European American women, but not for ethnic minority women, both forms of psychological distress were significant mediators of the sexual assault/hazardous drinking relationship. In contrast, among all ethnic groups, the relationship between sexual assault and both forms of psychological distress was mediated by the use of sexual behavior as an affect regulation strategy. Results support a need to evaluate the assault experiences of ethnically diverse women, as well as the impact of the assault on their postassault experiences including health risk behaviors and psychological adjustment. Additionally, results suggest that practitioners should carefully assess health risk behaviors among victims of sexual assault and be aware that there may be differences in the risk factors and motives for these behaviors among women of various ethnic backgrounds. PMID- 24223468 TI - Mixing-Driven Equilibrium Reactions in Multidimensional Fractional Advection Dispersion Systems. AB - We study instantaneous, mixing-driven, bimolecular equilibrium reactions in a system where transport is governed by a multidimensional space fractional dispersion equation. The superdiffusive, nonlocal nature of the system causes the location and magnitude of reactions that take place to change significantly from a classical Fickian diffusion model. In particular, regions where reaction rates would be zero for the Fickian case become regions where the maximum reaction rate occurs when anomalous dispersion operates. We also study a global metric of mixing in the system, the scalar dissipation rate and compute its asymptotic scaling rates analytically. The scalar dissipation rate scales asymptotically as t-(d+alpha)/alpha , where d is the number of spatial dimensions and alpha is the fractional derivative exponent. PMID- 24223469 TI - CENTER CONDITIONS AND CYCLICITY FOR A FAMILY OF CUBIC SYSTEMS: COMPUTER ALGEBRA APPROACH. AB - Using methods of computational algebra we obtain an upper bound for the cyclicity of a family of cubic systems. We overcame the problem of nonradicality of the associated Bautin ideal by moving from the ring of polynomials to a coordinate ring. Finally, we determine the number of limit cycles bifurcating from each component of the center variety. PMID- 24223470 TI - Anxiety, Depression, and Coping Skills Among Mexican School Children: A Comparison of Students With and Without Learning Disabilities. AB - The purpose of this study was to compare severity and risk status for anxiety and depression with coping skills among 130 Mexican school children with learning disabilities (LD) and 130 school children without LD. This research is the first to explore the emotional difficulties of Mexican children with LD. Children completed the Spanish version of the Spence Children's Anxiety Scale and Children's Depression Inventory, and the Cuestionario de Afrontamiento (Coping Skills Questionnaire). Results indicated that a higher percentage of children with LD were at risk for anxiety (22.3% vs. 11.5%) and depression (32% vs. 18%). No statistically significant differences were found for coping skills. Results support the idea that there is an increased awareness of comorbid depression and anxiety among students with LD and a need to promote early identification and intervention in schools. Efforts should focus on better understanding the relationship between social-emotional difficulties and academic achievement and on developing effective interventions to support children with LD. PMID- 24223471 TI - Two-Stage Bayesian Model Averaging in Endogenous Variable Models. AB - Economic modeling in the presence of endogeneity is subject to model uncertainty at both the instrument and covariate level. We propose a Two-Stage Bayesian Model Averaging (2SBMA) methodology that extends the Two-Stage Least Squares (2SLS) estimator. By constructing a Two-Stage Unit Information Prior in the endogenous variable model, we are able to efficiently combine established methods for addressing model uncertainty in regression models with the classic technique of 2SLS. To assess the validity of instruments in the 2SBMA context, we develop Bayesian tests of the identification restriction that are based on model averaged posterior predictive p-values. A simulation study showed that 2SBMA has the ability to recover structure in both the instrument and covariate set, and substantially improves the sharpness of resulting coefficient estimates in comparison to 2SLS using the full specification in an automatic fashion. Due to the increased parsimony of the 2SBMA estimate, the Bayesian Sargan test had a power of 50 percent in detecting a violation of the exogeneity assumption, while the method based on 2SLS using the full specification had negligible power. We apply our approach to the problem of development accounting, and find support not only for institutions, but also for geography and integration as development determinants, once both model uncertainty and endogeneity have been jointly addressed. PMID- 24223472 TI - Informal and Illicit Entrepreneurs: Fighting for a Place in the Neoliberal Economic Order. AB - A panel at the 2007 meetings of the American Anthropological Association examined the working lives of illicit and informal entrepreneurs living in "the gaps" or "shadows" of neoliberal globalization. Panelists challenged dichotomies such as informal/formal and legal/illegal by examining the everyday practices of workers in diverse settings. Emphasis was placed on entrepreneurs' efforts to legitimate their activities and identities to themselves and others. PMID- 24223473 TI - Income and the Development of Effortful Control as Predictors of Teacher Reports of Preschool Adjustment. AB - This study examined the relations of income and children's effortful control to teacher reports of preschoolers' social competence and adjustment problems. This study tested whether changes in effortful control accounted for the effects of income on children's adjustment. A community sample (N=306) of preschool-age children (36-40 mos.) and their mothers, representing the full range of income (29% at or near poverty, 28% at or below the local median income), was used. Path analyses were used to test the prospective effects of income on rank-order changes in two aspects of effortful control, executive control and delay ability, which in turn, predicted teacher-reported adjustment problems and social competence. Lower income predicted smaller rank-order change in executive control, but did not predict changes in delay ability. Smaller rank-order change in delay ability predicted greater adjustment problems above the effect of income. Larger rank-order change in executive control predicted greater social competence and fewer adjustment problems above the effect of income. These findings provided some support for the hypothesis that disruptions in the development of effortful control related to low income might account for the effects of low income on young children's adjustment. Effortful control is potentially a fruitful target for intervention, particularly among children living in low income and poverty. PMID- 24223474 TI - Model-based measurement of food portion size for image-based dietary assessment using 3D/2D registration. AB - Dietary assessment is important in health maintenance and intervention in many chronic conditions, such as obesity, diabetes, and cardiovascular disease. However, there is currently a lack of convenient methods for measuring the volume of food (portion size) in real-life settings. We present a computational method to estimate food volume from a single photographical image of food contained in a typical dining plate. First, we calculate the food location with respect to a 3D camera coordinate system using the plate as a scale reference. Then, the food is segmented automatically from the background in the image. Adaptive thresholding and snake modeling are implemented based on several image features, such as color contrast, regional color homogeneity and curve bending degree. Next, a 3D model representing the general shape of the food (e.g., a cylinder, a sphere, etc.) is selected from a pre-constructed shape model library. The position, orientation and scale of the selected shape model are determined by registering the projected 3D model and the food contour in the image, where the properties of the reference are used as constraints. Experimental results using various realistically shaped foods with known volumes demonstrated satisfactory performance of our image based food volume measurement method even if the 3D geometric surface of the food is not completely represented in the input image. PMID- 24223475 TI - Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B. AB - Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF- kappa B-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF- kappa B, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor- alpha (TNF- alpha ), interleukin-1 beta (IL-1 beta ), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF- kappa B p65, TNF- alpha , IL-1 beta , IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases. PMID- 24223477 TI - Collectivity, Distributivity, and the Interpretation of Plural Numerical Expressions in Child and Adult Language. AB - Sentences containing plural numerical expressions (e.g., two boys) can give rise to two interpretations (collective and distributive), arising from the fact that their representation admits of a part-whole structure. We present the results of a series of experiments designed to explore children's understanding of this distinction and its implications for the acquisition of linguistic expressions with number words. We show that preschoolers access both interpretations, indicating that they have the requisite linguistic and conceptual machinery to generate the corresponding representations. Furthermore, they can shift their interpretation in response to structural and lexical manipulations. However, they are not fully adult-like: unlike adults, they are drawn to the distributive interpretation, and are not yet aware of the lexical semantics of each and together, which should favor one or another interpretation. This research bridges a gap between a well-established body of work in cognitive psychology on the acquisition of number words and more recent work investigating children's knowledge of the syntactic and semantic properties of sentences featuring numerical expressions. PMID- 24223476 TI - The role of mannose-binding lectin in severe sepsis and septic shock. AB - Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice. PMID- 24223478 TI - Cryogenic Etching of Silicon: An Alternative Method For Fabrication of Vertical Microcantilever Master Molds. AB - This paper examines the use of deep reactive ion etching (DRIE) of silicon with fluorine high-density plasmas at cryogenic temperatures to produce silicon master molds for vertical microcantilever arrays used for controlling substrate stiffness for culturing living cells. The resultant profiles achieved depend on the rate of deposition and etching of a SiO x F y polymer, which serves as a passivation layer on the sidewalls of the etched structures in relation to areas that have not been passivated with the polymer. We look at how optimal tuning of two parameters, the O2 flow rate and the capacitively coupled plasma (CCP) power, determine the etch profile. All other pertinent parameters are kept constant. We examine the etch profiles produced using e-beam resist as the main etch mask, with holes having diameters of 750 nm, 1 um, and 2 um. PMID- 24223479 TI - Differentiation of Functional Groups and Biologically Relevant Anions Using AT PAMAM Dendrimers. AB - Biological anions have often proven to be difficult analytes to differentiate in solution. Many of the anions bear similar structural characteristics and similar charge states. Using a commercially available indicator and AT-PAMAM dendrimers, a sensing ensemble for a number of biological anions was constructed. The system was able to identify each of the different analytes as well as the regioisomers of three different tricarboxylates. The system shows responsiveness to not only functional group identity but also the charge state and identity of the anionic species. PMID- 24223480 TI - Inference for Size Demography from Point Pattern Data using Integral Projection Models. AB - Population dynamics with regard to evolution of traits has typically been studied using matrix projection models (MPMs). Recently, to work with continuous traits, integral projection models (IPMs) have been proposed. Imitating the path with MPMs, IPMs are handled first with a fitting stage, then with a projection stage. Fitting these models has so far been done only with individual-level transition data. These data are used to estimate the demographic functions (survival, growth, fecundity) that comprise the kernel of the IPM specification. Then, the estimated kernel is iterated from an initial trait distribution to project steady state population behavior under this kernel. When trait distributions are observed over time, such an approach does not align projected distributions with these observed temporal benchmarks. The contribution here, focusing on size distributions, is to address this issue. Our concern is that the above approach introduces an inherent mismatch in scales. The redistribution kernel in the IPM proposes a mechanistic description of population level redistribution. A kernel of the same functional form, fitted to data at the individual level, would provide a mechanistic model for individual-level processes. Resulting parameter estimates and the associated estimated kernel are at the wrong scale and do not allow population-level interpretation. Our approach views the observed size distribution at a given time as a point pattern over a bounded interval. We build a three-stage hierarchical model to infer about the dynamic intensities used to explain the observed point patterns. This model is driven by a latent deterministic IPM and we introduce uncertainty by having the operating IPM vary around this deterministic specification. Further uncertainty arises in the realization of the point pattern given the operating IPM. Fitted within a Bayesian framework, such modeling enables full inference about all features of the model. Such dynamic modeling, optimized by fitting data observed over time, is better suited to projection. Exact Bayesian model fitting is very computationally challenging; we offer approximate strategies to facilitate computation. We illustrate with simulated data examples as well as well as a set of annual tree growth data from Duke Forest in North Carolina. A further example shows the benefit of our approach, in terms of projection, compared with the foregoing individual level fitting. PMID- 24223481 TI - Role of Photodynamic Therapy for the Upper Gut. AB - It may be questioned if PDT is still relevant for practicing gastroenterologists since other types of therapy have currently gained momentum. Important aspects of PDT that continue its development are it's intrinsic applicability to the luminal GI tract where there are often areas of mechanical narrowing, unusual topography, and difficult accessibility where a modality that does not require contact or optical visualization has advantages. Although not used as often in the upper gastrointestinal tract for it's original approved indications such as esophageal cancer or Barrett's esophagus, its value in biliary lesions appears to be well substantiated. In this paper, we will review its current application in the upper gastrointestinal tract. PMID- 24223482 TI - Spatial extreme value analysis to project extremes of large-scale indicators for severe weather. AB - Concurrently high values of the maximum potential wind speed of updrafts (Wmax) and 0-6 km wind shear (Shear) have been found to represent conducive environments for severe weather, which subsequently provides a way to study severe weather in future climates. Here, we employ a model for the product of these variables (WmSh) from the National Center for Atmospheric Research/United States National Center for Environmental Prediction reanalysis over North America conditioned on their having extreme energy in the spatial field in order to project the predominant spatial patterns of WmSh. The approach is based on the Heffernan and Tawn conditional extreme value model. Results suggest that this technique estimates the spatial behavior of WmSh well, which allows for exploring possible changes in the patterns over time. While the model enables a method for inferring the uncertainty in the patterns, such analysis is difficult with the currently available inference approach. A variation of the method is also explored to investigate how this type of model might be used to qualitatively understand how the spatial patterns of WmSh correspond to extreme river flow events. A case study for river flows from three rivers in northwestern Tennessee is studied, and it is found that advection of WmSh from the Gulf of Mexico prevails while elsewhere, WmSh is generally very low during such extreme events. (c) 2013 The Authors. Environmetrics published by JohnWiley & Sons, Ltd. PMID- 24223483 TI - Revision of the rhinoceros beetle genus Oryctophileurus Kolbe with description of a new species, the male of O. varicosus Prell, and notes on biogeography (Scarabaeoidea, Dynastinae, Phileurini). AB - The genus Oryctophileurus is reviewed and its validity is supported by a combination of the following apomorphic characters: a single cephalic horn with lateral carina, pronotal cavity with ocellate punctures and two teeth or tubercles close behind the anterior pronotal margin. The male of Oryctophileurus varicosus Prell, 1934, is described for the first time. A new species, Oryctophileurus guerrai Perger & Grossi sp. n., from subhumid Tucuman-Bolivian forest in the Southern Bolivian Andes is described. The new species is distinguished from its closest relative, O. armicollis Prell, 1911, by a narrower distance between the inner teeth of the dorsal pronotal protuberances and a reduced area of weakly developed ocellate punctures above the posterolateral pronotal margin. The occurrence of Oryctophileurus species in areas of endemism along the eastern slope of the tropical Andes suggests that these populations represent biogeographic "relicts", and the discovery of Oryctophileurus guerrai sp. n. in the southern Bolivian Andes suggests that this area is underrated with respect to insect diversity and endemism. PMID- 24223484 TI - A new species of the genus Karnyothrips (Thysanoptera, Phlaeothripidae) from China. AB - Karnyothrips cyathomorphus sp. n. (Phlaeothripidae: Phlaeothripinae) is described as a new apterous species in the genus Karnyothrips Watson 1923, and it represents the fourth species of the genus to be recorded from China. A key to the Chinese species is given. PMID- 24223485 TI - A new species of Tangius from north India (Coleoptera, Staphylinidae, Pselaphinae). AB - Tangius indicus sp. n. (Batrisitae: Batrisini) is described and illustrated from the Indian States of Meghalaya (Khasi Hills, type locality) and West Bengal (Darjeeling). Specimens of the new species are similar to those of the recently described T. glabellus Yin & Li from Tibet, Southwest China, and can be separated only by minor differences of the male features. PMID- 24223486 TI - GenSeq: An updated nomenclature and ranking for genetic sequences from type and non-type sources. AB - An improved and expanded nomenclature for genetic sequences is introduced that corresponds with a ranking of the reliability of the taxonomic identification of the source specimens. This nomenclature is an advancement of the "Genetypes" naming system, which some have been reluctant to adopt because of the use of the "type" suffix in the terminology. In the new nomenclature, genetic sequences are labeled "genseq," followed by a reliability ranking (e.g., 1 if the sequence is from a primary type), followed by the name of the genes from which the sequences were derived (e.g., genseq-1 16S, COI). The numbered suffix provides an indication of the likely reliability of taxonomic identification of the voucher. Included in this ranking system, in descending order of taxonomic reliability, are the following: sequences from primary types - "genseq-1," secondary types - "genseq-2," collection-vouchered topotypes - "genseq-3," collection-vouchered non types - "genseq-4," and non-types that lack specimen vouchers but have photo vouchers - "genseq-5." To demonstrate use of the new nomenclature, we review recently published new-species descriptions in the ichthyological literature that include DNA data and apply the GenSeq nomenclature to sequences referenced in those publications. We encourage authors to adopt the GenSeq nomenclature (note capital "G" and "S" when referring to the nomenclatural program) to provide a searchable tag (e.g., "genseq"; note lowercase "g" and "s" when referring to sequences) for genetic sequences from types and other vouchered specimens. Use of the new nomenclature and ranking system will improve integration of molecular phylogenetics and biological taxonomy and enhance the ability of researchers to assess the reliability of sequence data. We further encourage authors to update sequence information on databases such as GenBank whenever nomenclatural changes are made. PMID- 24223487 TI - New and little known species of oribatid mites of the family Haplozetidae (Acari, Oribatida) from Ecuador. AB - We described two new species, Haplozetes paraminimicoma sp. n. and Protoribates ecuadoriensis sp. n. from Ecuador. Additionally, a detailed supplementary description of Trachyoribates (Rostrozetes) glaber (Beck, 1965) is given on the basis of Ecuadorian specimens, which was known previously only from Peru. An annotated checklist of all identified taxa of Haplozetidae from Ecuador is presented. PMID- 24223488 TI - Molecular phylogenetic evidence supports a new family of octocorals and a new genus of Alcyoniidae (Octocorallia, Alcyonacea). AB - Molecular phylogenetic evidence indicates that the octocoral family Alcyoniidae is highly polyphyletic, with genera distributed across Octocorallia in more than 10 separate clades. Most alcyoniid taxa belong to the large and poorly resolved Holaxonia-Alcyoniina clade of octocorals, but members of at least four genera of Alcyoniidae fall outside of that group. As a first step towards revision of the family, we describe a new genus, Parasphaerasclera gen. n., and family, Parasphaerascleridae fam. n., of Alcyonacea to accommodate species of Eleutherobia Putter, 1900 and Alcyonium Linnaeus, 1758 that have digitiform to digitate or lobate growth forms, completely lack sclerites in the polyps, and have radiates or spheroidal sclerites in the colony surface and interior. Parasphaerascleridae fam. n. constitutes a well-supported clade that is phylogenetically distinct from all other octocoral taxa. We also describe a new genus of Alcyoniidae, Sphaerasclera gen. n., for a species of Eleutherobia with a unique capitate growth form. Sphaerasclera gen. n. is a member of the Anthomastus Corallium clade of octocorals, but is morphologically and genetically distinct from Anthomastus Verrill, 1878 and Paraminabea Williams & Alderslade, 1999, two similar but dimorphic genera of Alcyoniidae that are its sister taxa. In addition, we have re-assigned two species of Eleutherobia that have clavate to capitate growth forms, polyp sclerites arranged to form a collaret and points, and spindles in the colony interior to Alcyonium, a move that is supported by both morphological and molecular phylogenetic evidence. PMID- 24223489 TI - Nomenclatural changes in the tribe Empoascini of the subfamily Typhlocybinae (Hemiptera, Cicadellidae). AB - One genus and species are synonymized in the tribe Empoascini of the subfamily Typhlocybinae. Bhatasca Dworakowska, 1995is a junior synonym of Alebrasca Hayashi & Okada, 1994, Bhatasca rectangulata Qin & Zhang, 2011is a junior synonym of Alebrasca actinidiae Hayashi & Okada, 1994. Furthermore, Bhatasca expansa is (necessarily) transferred to the genus Alebrasca. PMID- 24223490 TI - Integrative taxonomy resolves the cryptic and pseudo-cryptic Radula buccinifera complex (Porellales, Jungermanniopsida), including two reinstated and five new species. AB - Molecular data from three chloroplast markers resolve individuals attributable to Radula buccinifera in six lineages belonging to two subgenera, indicating the species is polyphyletic as currently circumscribed. All lineages are morphologically diagnosable, but one pair exhibits such morphological overlap that they can be considered cryptic. Molecular and morphological data justify the re-instatement of a broadly circumscribed ecologically variable R. strangulata, of R. mittenii, and the description of five new species. Two species Radula mittenii Steph. and R. notabilis sp. nov. are endemic to the Wet Tropics Bioregion of north-east Queensland, suggesting high diversity and high endemism might characterise the bryoflora of this relatively isolated wet-tropical region. Radula demissa sp. nov. is endemic to southern temperate Australasia, and like R. strangulata occurs on both sides of the Tasman Sea. Radula imposita sp. nov. is a twig and leaf epiphyte found in association with waterways in New South Wales and Queensland. Another species, R. pugioniformis sp. nov., has been confused with Radula buccinifera but was not included in the molecular phylogeny. Morphological data suggest it may belong to subg. Odontoradula. Radula buccinifera is endemic to Australia including Western Australia and Tasmania, and to date is known from south of the Clarence River on the north coast of New South Wales. Nested within R. buccinifera is a morphologically distinct plant from Norfolk Island described as R. anisotoma sp. nov. Radula australiana is resolved as monophyletic, sister to a species occurring in east coast Australian rainforests, and nesting among the R. buccinifera lineages with strong support. The molecular phylogeny suggests several long-distance dispersal events may have occurred. These include two east west dispersal events from New Zealand to Tasmania and south-east Australia in R. strangulata, one east-west dispersal event from Tasmania to Western Australia in R. buccinifera, and at least one west-east dispersal from Australia to New Zealand in R. australiana. Another west-east dispersal event from Australia to Norfolk Island may have led to the budding speciation of R. anisotoma. In contrast, Radula demissa is phylogeographically subdivided into strongly supported clades either side of the Tasman Sea, suggesting long distance dispersal is infrequent in this species. PMID- 24223491 TI - Solution conformation of 2-aminopurine (2-AP) dinucleotide determined by ultraviolet 2D fluorescence spectroscopy (UV-2D FS). AB - We have observed the conformation-dependent electronic coupling between the monomeric subunits of a dinucleotide of 2-aminopurine (2-AP), a fluorescent analog of the nucleic acid base adenine. This was accomplished by extending two dimensional fluorescence spectroscopy (2D FS) - a fluorescence-detected variation of 2D electronic spectroscopy - to excite molecular transitions in the ultraviolet (UV) regime. A collinear sequence of four ultrafast laser pulses centered at 323 nm was used to resonantly excite the coupled transitions of 2-AP dinucleotide. The phases of the optical pulses were continuously swept at kilohertz frequencies, and the ensuing nonlinear fluorescence was phase synchronously detected at 370 nm. Upon optimization of a point-dipole coupling model to our data, we found that in aqueous buffer the 2-AP dinucleotide adopts an average conformation in which the purine bases are non-helically stacked (center-to-center distance R12 = 3.5 A +/- 0.5 A, twist angle theta12 = 5 degrees +/- 5 degrees ), which differs from the conformation of such adjacent bases in duplex DNA. These experiments establish UV-2D FS as a method for examining the local conformations of an adjacent pair of fluorescent nucleotides substituted into specific DNA or RNA constructs, which will serve as a powerful probe to interpret, in structural terms, biologically significant local conformational changes within the nucleic acid framework of protein-nucleic acid complexes. PMID- 24223493 TI - Synthesis and Biological Evaluation of Non-Hydrolizable 1,2,3-Triazole Linked Sialic Acid Derivatives as Neuraminidase Inhibitors. AB - alpha-Sialic acid azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper catalyzed azide-alkyne Huisgen cycloaddition ("click chemistry"). Our approach is to generate non-natural N-glycosides of sialic acid that are resistant to neuraminidase catalyzed hydrolysis as opposed to the natural O-glycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid derivatives has been synthesized in 71-89% yield. A disaccharide mimic of sialic acid has also been prepared using the alpha-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68% yield. A model sialic acid coated dendrimer was also synthesized from a per-propargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values were observed, comparable to the known sialidase inhibitor Neu5Ac2en. PMID- 24223494 TI - Simple Synthesis of Amides and Weinreb Amides via Use of PPh3 or Polymer Supported PPh3 and Iodine. AB - The combination of PPh3/I2 has been shown to be effective for conversion of a range of carboxylic acids to 2 degrees , 3 degrees , and Weinreb amides. Simplification of the procedure was possible with the use of polymer-supported PPh3/I2. Weinreb amides produced via the use of polymer-supported PPh3 could be filtered through a short silica gel plug and used in further transformations. Thus, use of polymer-supported PPh3 offers potential applicability to diversity oriented reactions. Formal total syntheses of apocynin and pratosine, as well as syntheses of anhydrolychorinone and hippadine, have been achieved via the use of this amide-forming method. An attempt has been made to gain insight into this reaction. PMID- 24223492 TI - Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges. AB - Cell penetrating peptides (CPPs) can deliver cell-impermeable therapeutic cargos into cells. In particular, CPP-cargo conjugates tend to accumulate inside cells by endocytosis. However, they often remain trapped inside endocytic organelles and fail to reach the cytosolic space of cells efficiently. In this review, the evidence for CPP-mediated endosomal escape is discussed. In addition, several strategies that have been utilized to enhance the endosomal escape of CPP-cargos are described. The recent development of branched systems that display multiple copies of a CPP is presented. The use of viral or synthetic peptides that can disrupt the endosomal membrane upon activation by the low pH of endosomes is also discussed. Finally, we survey how CPPs labeled with chromophores can be used in combination with light to stimulate endosomal lysis. The mechanisms and challenges associated with these intracellular delivery methodologies are discussed. PMID- 24223495 TI - Estimates of age-specific reductions in HIV prevalence in Uganda: Bayesian melding estimation and probabilistic population forecast with an HIV-enabled cohort component projection model. AB - BACKGROUND: Much of our knowledge of the epidemiology and demography of HIV epidemics in Africa is derived from models fit to sparse, non-representative data. These often average over age and other important dimensions, rarely quantify uncertainty, and typically do not impose consistency on the epidemiology and the demography of the population. OBJECTIVE: This work conducts an empirical investigation of the history of the HIV epidemic in Uganda and Tanzania through the late 1990s, focusing on sex-age-specific incidence, uses those results to produce probabilistic forecasts of HIV prevalence ten years later, and compares those to measures of HIV prevalence at the later time to describe the sex-age pattern of changes in prevalence over the intervening period. METHODS: We adapt an epidemographic model of a population affected by HIV so that its parameters can be estimated using both the Bayesian melding with IMIS estimation method and maximum likelihood methods. Using the Bayesian version of the model we produce probabilistic forecasts of the population with HIV. RESULTS: We produce estimates of sex-age-specific HIV incidence in Uganda and Tanzania in the late 1990s, produce probabilistic forecasts of the HIV epidemics in Uganda and Tanzania during the early 2000s, describe the sex-age pattern of changes in HIV prevalence in Uganda during the early 2000s, and compare the performance and results of the Bayesian and maximum likelihood estimation procedures. CONCLUSIONS: We demonstrate that: (1) it is possible to model HIV epidemics in Africa taking account of sex and age, (2) there are important advantages to the Bayesian estimation method, including rigorous quantification of uncertainty and the ability to make probabilistic forecasts, and (3) that there were important age specific changes in HIV incidence in Uganda during the early 2000s. PMID- 24223496 TI - Care of the body: spaces of practice. PMID- 24223497 TI - Do Community and Caregiver Factors Influence Hospice Use at the End of Life Among Older Adults With Alzheimer Disease? AB - Hospice is an underused service among people with Alzheimer disease. This study used the Hospice Use Model to examine community, care recipient, and caregiver characteristics associated with hospice use before death among 145 community dwelling care recipients with Alzheimer disease and their caregivers. Secondary analysis using logistic regression modeling indicated that older age, male gender, black race, and better functional health of care recipients with Alzheimer disease were associated with a decreased likelihood of using hospice (model chi25 = 23.5, P = .0003). Moreover, care recipients recruited from an Alzheimer clinic were more likely to use hospice than those recruited from adult day-care centers. Caregiver factors were not independent predictors of hospice use. However, there was a significant interaction between hours of care provided each week and recruitment site. Among care recipients from the Alzheimer clinic, the probability of hospice use increased as caregiving intensity increased. This relationship was reversed in care recipients from day-care centers. Results suggest that adult day-care centers need to partner with hospice programs in the community. In conclusion, care recipient and community service factors influence hospice use in individuals with Alzheimer disease. PMID- 24223498 TI - A biomechanical model of the inner ear: numerical simulation of the caloric test. AB - Whether two vertical semicircular canals can receive thermal stimuli remains controversial. This study examined the caloric response in the three semicircular canals to the clinical hot caloric test using the finite element method. The results of the developed model showed the horizontal canal (HC) cupula maximally deflected to the utricle side by approximately 3 MUm during the hot supine test. The anterior canal cupula began to receive the caloric stimuli about 20 s after the HC cupula, and it maximally deflected to the canal side by 0.55 MUm. The posterior canal cupula did not receive caloric stimuli until approximately 40 s after the HC cupula, and it maximally deflected to the canal side by 0.34 MUm. Although the endolymph flow and the cupular deformation change with respect to the head position during the test, the supine test ensures the maximal caloric response in the HC, but no substantial improvement for the responses of the two vertical canals was observed. In conclusion, while the usual supine test is the optimum test for evaluating the functions of the inner ear, more irrigation time is needed in order to effectively clinically examine the vertical canals. PMID- 24223499 TI - Risk of coronary heart disease among HIV-infected patients: a multicenter study in Brazil. AB - Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 +/- 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score >=10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score >=10 was similar between regions for males, patients aged >=60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population. PMID- 24223500 TI - Pyrolysis of table sugar. AB - Table sugars were pyrolyzed at different temperatures (300, 400, and 500 degrees C) in a fixed-bed reactor. The effect of pyrolysis temperature on yields of liquid, solid, and gaseous products was investigated. As expected the yield of liquid products gradually increased and the yield of solid products gradually decreased when the pyrolysis temperature was raised. The yield of liquid products was greatest (52 wt%) at 500 degrees C. The composition of bio-oils extracted with diethyl ether was identified by means of gas chromatography mass spectrometry (GC-MS), nuclear magnetic resonance ((1)H-NMR), and Fourier transform infrared spectroscopy (FTIR). The following compounds were observed in bio-oils produced from the pyrolysis of table sugar at 500 degrees C: 1,4:3,6 dianhydro- alpha -d-glucopyranose, 5-(hydroxymethyl) furfural, 5-acetoxymethyl-2 furaldehyde, and cyclotetradecane liquid product. The relative concentration of 5 (hydroxymethyl) furfural was the highest in bio-oils obtained from pyrolysis of table sugars at 500 degrees C. PMID- 24223501 TI - A method to dynamic stochastic multicriteria decision making with log-normally distributed random variables. AB - We investigate the dynamic stochastic multicriteria decision making (SMCDM) problems, in which the criterion values take the form of log-normally distributed random variables, and the argument information is collected from different periods. We propose two new geometric aggregation operators, such as the log normal distribution weighted geometric (LNDWG) operator and the dynamic log normal distribution weighted geometric (DLNDWG) operator, and develop a method for dynamic SMCDM with log-normally distributed random variables. This method uses the DLNDWG operator and the LNDWG operator to aggregate the log-normally distributed criterion values, utilizes the entropy model of Shannon to generate the time weight vector, and utilizes the expectation values and variances of log normal distributions to rank the alternatives and select the best one. Finally, an example is given to illustrate the feasibility and effectiveness of this developed method. PMID- 24223502 TI - Assessment of antioxidant and cytotoxicity activities of saponin and crude extracts of Chlorophytum borivilianum. AB - The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1 picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and beta carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 +/- 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL(-1)), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL(-1)). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF 7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line. PMID- 24223503 TI - Parallel PWMs based fully digital transmitter with wide carrier frequency range. AB - The carrier-frequency (CF) and intermediate-frequency (IF) pulse-width modulators (PWMs) based on delay lines are proposed, where baseband signals are conveyed by both positions and pulse widths or densities of the carrier clock. By combining IF-PWM and precorrected CF-PWM, a fully digital transmitter with unit-delay autocalibration is implemented in 180 nm CMOS for high reconfiguration. The proposed architecture achieves wide CF range of 2 M-1 GHz, high power efficiency of 70%, and low error vector magnitude (EVM) of 3%, with spectrum purity of 20 dB optimized in comparison to the existing designs. PMID- 24223504 TI - Reliability evaluation based on different distributions of random load. AB - The reliability models of the components under the nonstationary random load are developed in this paper. Through the definition of the distribution of the random load, it can be seen that the conventional load-strength interference model is suitable for the calculation of the static reliability of the components, which does not reflect the dynamic change in the reliability and cannot be used to evaluate the dynamic reliability. Therefore, by developing an approach to converting the nonstationary random load into the random load whose pdf is the same at each moment when the random load applies, the reliability model based on the longitudinal distribution is derived. Moreover, through the definition of the transverse standard load and the transverse standard load coefficient, the reliability model based on the transverse distribution is derived. When the occurrence of the random load follows the Poisson process, the dynamic reliability models considering the strength degradation are derived. These models take the correlation between the random load and the strength into consideration. The result shows that the dispersion of the initial strength and that of the transverse standard load coefficient have great influences on the reliability and the hazard rate of the components. PMID- 24223505 TI - Flavocytochrome b2-based enzymatic method of L-lactate assay in food products. AB - L-lactate, a key metabolite of the anaerobic glycolytic pathway, plays an important role as a biomarker in medicine, in the nutritional sector and food quality control. For these reasons, there is a need for very specific, sensitive, and simple analytical methods for the accurate L-lactate measuring. A new highly selective enzymatic method for L-lactate determination based on the use of flavocytochrome b 2 (EC 1.1.2.3; FC b 2) isolated from the recombinant strain of the yeast Hansenula polymorpha has been developed. A proposed enzymatic method exploits an enzymatic oxidation of L-lactate to pyruvate coupled with nitrotetrazolium blue (NTZB) reduction to a colored product, formazan. The maximal absorption peak of the colored product is near lambda = 525 nm and the linear range is observed in the interval 0.005-0.14 mM of L-lactate. The main advantages of the proposed method when compared to the LDH-based routine approaches are a higher sensitivity (2.0 MUM of L-lactate), simple procedure of analysis, usage of inexpensive, nontoxic reagents, and small amount of the enzyme. Enzymatic oxidation of L-lactate catalyzed by flavocytochrome b 2 and coupled with formazan production from nitrotetrazolium blue was shown to be used for L-lactate assay in food samples. A high correlation between results of the proposed method and reference ones proves the possibility to use flavocytochrome b 2-catalysed reaction for enzymatic measurement of L-lactate in biotechnology and food chemistry. PMID- 24223506 TI - Improved algorithm for gradient vector flow based active contour model using global and local information. AB - Active contour models are used to extract object boundary from digital image, but there is poor convergence for the targets with deep concavities. We proposed an improved approach based on existing gradient vector flow methods. Main contributions of this paper are a new algorithm to determine the false part of active contour with higher accuracy from the global force of gradient vector flow and a new algorithm to update the external force field together with the local information of magnetostatic force. Our method has a semidynamic external force field, which is adjusted only when the false active contour exists. Thus, active contours have more chances to approximate the complex boundary, while the computational cost is limited effectively. The new algorithm is tested on irregular shapes and then on real images such as MRI and ultrasound medical data. Experimental results illustrate the efficiency of our method, and the computational complexity is also analyzed. PMID- 24223507 TI - Quantum control and quantum information technology. PMID- 24223508 TI - The serological and virological investigation of canine adenovirus infection on the dogs. AB - Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV 2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188-54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188-45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs. PMID- 24223509 TI - Trichotomy for dynamical systems in Banach spaces. AB - We construct a framework for the study of dynamical systems that describe phenomena from physics and engineering in infinite dimensions and whose state evolution is set out by skew-evolution semiflows. Therefore, we introduce the concept of omega-trichotomy. Characterizations in a uniform setting are proved, using techniques from the domain of nonautonomous evolution equations with unbounded coefficients, and connections with the classic notion of trichotomy are given. The statements are sustained by several examples. PMID- 24223510 TI - Microstructural evolution during DPRM process of semisolid ledeburitic D2 tool steel. AB - Semisolid metal processing is a relatively new technology that offers several advantages over liquid processing and solid processing because of the unique behaviour and characteristic microstructure of metals in this state. With the aim of finding a minimum process chain for the manufacture of high-quality production at minimal cost for forming, the microstructural evolution of the ledeburitic AISI D2 tool steel in the semisolid state was studied experimentally. The potential of the direct partial remelting (DPRM) process for the production of AISI D2 with a uniform globular microstructure was revealed. The liquid fraction was determined using differential scanning calorimetry. The microstructures of the samples were investigated using an optical microscope and a scanning electron microscope equipped with an energy dispersive spectroscopy analyser, while X-ray phase analysis was performed to identify the phase evolution and the type of carbides. Mechanical characterisation was completed by hardness measurements. The typical microstructure after DPRM consists of metastable austenite which was located particularly in the globular grains (average grain size about 50 MU m), while the remaining interspaces were filled by precipitated eutectic carbides on the grain boundaries and lamellar network. PMID- 24223512 TI - In vitro effect of sodium fluoride on malondialdehyde concentration and on superoxide dismutase, catalase, and glutathione peroxidase in human erythrocytes. AB - The aim of this paper was to describe the in vitro effect of sodium fluoride (NaF) on the specific activity of the major erythrocyte antioxidant enzymes, as well as on the membrane malondialdehyde concentration, as indicators of oxidative stress. For this purpose, human erythrocytes were incubated with NaF (0, 7, 28, 56, and 100 MUg/mL) or NaF (100 MUg/mL) + vitamin E (1, 2.5, 5 and 10 MUg/mL). The malondialdehyde (MDA) concentration on the surface of the erythrocytes was determined, as were the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GlPx). Our results demonstrated that erythrocytes incubated with increasing NaF concentrations had an increased MDA concentration, along with decreased activity of antioxidant enzymes. The presence of vitamin E partially reversed the toxic effects of NaF on erythrocytes. These findings suggest that NaF induces oxidative stress in erythrocytes in vitro, and this stress is partially reversed by the presence of vitamin E. PMID- 24223513 TI - Integration of agronomic practices with herbicides for sustainable weed management in aerobic rice. AB - Till now, herbicide seems to be a cost effective tool from an agronomic view point to control weeds. But long term efficacy and sustainability issues are the driving forces behind the reconsideration of herbicide dependent weed management strategy in rice. This demands reappearance of physical and cultural management options combined with judicious herbicide application in a more comprehensive and integrated way. Keeping those in mind, some agronomic tools along with different manual weeding and herbicides combinations were evaluated for their weed control efficacy in rice under aerobic soil conditions. Combination of competitive variety, higher seeding rate, and seed priming resulted in more competitive cropping system in favor of rice, which was reflected in lower weed pressure, higher weed control efficiency, and better yield. Most of the herbicides exhibited excellent weed control efficiency. Treatments comprising only herbicides required less cost involvement but produced higher net benefit. On the contrary, treatments comprising both herbicide and manual weeding required high cost involvement and thus produced lower net benefit. Therefore, adoption of competitive rice variety, higher seed rate, and seed priming along with spraying different early-postemergence herbicides in rotation at 10 days after seeding (DAS) followed by a manual weeding at 30 DAS may be recommended from sustainability view point. PMID- 24223514 TI - Integrating Behavioral HIV Interventions into Biomedical Prevention Trials with Youth: Lessons from Chicago's Project PrEPare. AB - On the heels of several trials demonstrating the efficacy of pre-exposure prophylaxis (PrEP) and the recent approval by the FDA of the supplemental indication for Truvada as PrEP, researchers, advocates, and community providers are calling for the investigation of implementation strategies that combine behavioral interventions with biomedical prevention. This paper describes the modification and integration of an evidence-based group-level intervention into a small PrEP pilot trial with young men who have sex with men (YMSM). The behavioral intervention as well as ongoing risk reduction counseling sessions were found to be highly acceptable among a sample of racially diverse YMSM. PMID- 24223515 TI - Teaming Up with Girl Scouts for Online Nutrition Information. AB - Three librarians at LSU Health Shreveport partnered with staff members at the Shreveport service center staff of the Girl Scouts of Louisiana - Pines to the Gulf to teach girls about nutrition. The librarians provided instruction to the staff on healthelinks, MedlinePlus, and the other National Library of Medicine databases. They worked with the staff to incorporate these online resources into the nutrition curriculum for the Girl Scout leaders to use with their troops. They also provided two laptop computers, promotional items, and teaching aids. The program was repeated in the summer for week-long day camps designed to introduce girls to Scouting. The librarians had the opportunity to work directly with over one hundred girls at these camps to introduce them to authoritative, age-appropriate web sites on nutrition. PMID- 24223516 TI - Reflections on the cost of "low-cost" whole genome sequencing: framing the health policy debate. AB - The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy. PMID- 24223517 TI - Does the shoe fit? Real versus imagined ecological footprints. PMID- 24223518 TI - The shoe fits, but the footprint is larger than earth. PMID- 24223519 TI - The ecological footprint remains a misleading metric of global sustainability. PMID- 24223522 TI - Hardship strengthens mutual bonds. PMID- 24223521 TI - Water stress strengthens mutualism among ants, trees, and scale insects. AB - Abiotic environmental variables strongly affect the outcomes of species interactions. For example, mutualistic interactions between species are often stronger when resources are limited. The effect might be indirect: water stress on plants can lead to carbon stress, which could alter carbon-mediated plant mutualisms. In mutualistic ant-plant symbioses, plants host ant colonies that defend them against herbivores. Here we show that the partners' investments in a widespread ant-plant symbiosis increase with water stress across 26 sites along a Mesoamerican precipitation gradient. At lower precipitation levels, Cordia alliodora trees invest more carbon in Azteca ants via phloem-feeding scale insects that provide the ants with sugars, and the ants provide better defense of the carbon-producing leaves. Under water stress, the trees have smaller carbon pools. A model of the carbon trade-offs for the mutualistic partners shows that the observed strategies can arise from the carbon costs of rare but extreme events of herbivory in the rainy season. Thus, water limitation, together with the risk of herbivory, increases the strength of a carbon-based mutualism. PMID- 24223520 TI - N-wasp is essential for the negative regulation of B cell receptor signaling. AB - Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR) signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of signaling remains elusive. Using genetically manipulated mouse models and total internal reflection fluorescence microscopy, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP), which is coexpressed with WASP in all immune cells, is a critical negative regulator of B-cell signaling. B-cell specific N-WASP gene deletion causes enhanced and prolonged BCR signaling and elevated levels of autoantibodies in the mouse serum. The increased signaling in N-WASP knockout B cells is concurrent with increased accumulation of F-actin at the B-cell surface, enhanced B-cell spreading on the antigen-presenting membrane, delayed B-cell contraction, inhibition in the merger of signaling active BCR microclusters into signaling inactive central clusters, and a blockage of BCR internalization. Upon BCR activation, WASP is activated first, followed by N-WASP in mouse and human primary B cells. The activation of N-WASP is suppressed by Bruton's tyrosine kinase-induced WASP activation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibits WASP activation. Our results reveal a new mechanism for the negative regulation of BCR signaling and broadly suggest an actin-mediated mechanism for signaling down regulation. PMID- 24223523 TI - Measles outbreak response immunization is context-specific: insight from the recent experience of Medecins Sans Frontieres. AB - Andrea Minetti and colleagues compare measles outbreak responses from the Democratic Republic of the Congo and Malawi and argue that outbreak response strategies should be tailored to local measles epidemiology. Please see later in the article for the Editors' Summary. PMID- 24223524 TI - Antenatal syphilis screening using point-of-care testing in Sub-Saharan African countries: a cost-effectiveness analysis. AB - BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability adjusted life years (DALYs) averted. METHODS AND FINDINGS: The decision analytic model reflected the perspective of the national health care system and was based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin. Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US$11 (range: US$2-US$48). Screening remains highly cost effective even if the average prevalence falls from the current rate of 3.1% (range: 0.6%-14.0%) to 0.038% (range: 0.002%-0.113%). Universal antenatal screening of pregnant women in clinics may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US$20.8 million. CONCLUSIONS: Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis screening using the ICS test. Please see later in the article for the Editors' Summary. PMID- 24223525 TI - From ideals to tools: applying human rights to maternal health. AB - Alicia Yamin argues that applying human rights frameworks and approaches to maternal health offers strategies and tools to address the root causes of maternal morbidity and mortality within and beyond health systems, in addition to addressing other violations of women's sexual and reproductive health and rights. Please see later in the article for the Editors' Summary. PMID- 24223526 TI - Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. AB - BACKGROUND: Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. METHODS AND FINDINGS: Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders. Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%-10.8%) of global YLDs and dysthymia for 1.4% (0.9%-2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%-3.2%) of global DALYs and dysthymia for 0.5% (0.3%-0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%-3.8%) to 3.8% (3.0%-4.7%) of global DALYs. CONCLUSIONS: GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost effective interventions to reduce its burden. Please see later in the article for the Editors' Summary. PMID- 24223527 TI - Quantification of Drive-Response Relationships Between Residues During Protein Folding. AB - Mutual correlation and cooperativity are commonly used to describe residue residue interactions in protein folding/function. However, these metrics do not provide any information on the causality relationships between residues. Such drive-response relationships are poorly studied in protein folding/function and difficult to measure experimentally due to technical limitations. In this study, using the information theory transfer entropy (TE) that provides a direct measurement of causality between two times series, we have quantified the drive response relationships between residues in the folding/unfolding processes of four small proteins generated by molecular dynamics simulations. Instead of using a time-averaged single TE value, the time-dependent TE is measured with the Q scores based on residue-residue contacts and with the statistical significance analysis along the folding/unfolding processes. The TE analysis is able to identify the driving and responding residues that are different from the highly correlated residues revealed by the mutual information analysis. In general, the driving residues have more regular secondary structures, are more buried, and show greater effects on the protein stability as well as folding and unfolding rates. In addition, the dominant driving and responding residues from the TE analysis on the whole trajectory agree with those on a single folding event, demonstrating that the drive-response relationships are preserved in the non equilibrium process. Our study provides detailed insights into the protein folding process and has potential applications in protein engineering and interpretation of time-dependent residue-based experimental observables for protein function. PMID- 24223528 TI - AUTOMATED FORCE FIELD PARAMETERIZATION FOR NON-POLARIZABLE AND POLARIZABLE ATOMIC MODELS BASED ON AB INITIO TARGET DATA. AB - Classical molecular dynamics (MD) simulations based on atomistic models are increasingly used to study a wide range of biological systems. A prerequisite for meaningful results from such simulations is an accurate molecular mechanical force field. Most biomolecular simulations are currently based on the widely used AMBER and CHARMM force fields, which were parameterized and optimized to cover a small set of basic compounds corresponding to the natural amino acids and nucleic acid bases. Atomic models of additional compounds are commonly generated by analogy to the parameter set of a given force field. While this procedure yields models that are internally consistent, the accuracy of the resulting models can be limited. In this work, we propose a method, General Automated Atomic Model Parameterization (GAAMP), for generating automatically the parameters of atomic models of small molecules using the results from ab initio quantum mechanical (QM) calculations as target data. Force fields that were previously developed for a wide range of model compounds serve as initial guess, although any of the final parameter can be optimized. The electrostatic parameters (partial charges, polarizabilities and shielding) are optimized on the basis of QM electrostatic potential (ESP) and, if applicable, the interaction energies between the compound and water molecules. The soft dihedrals are automatically identified and parameterized by targeting QM dihedral scans as well as the energies of stable conformers. To validate the approach, the solvation free energy is calculated for more than 200 small molecules and MD simulations of 3 different proteins are carried out. PMID- 24223529 TI - Toward optimized potential functions for protein-protein interactions in aqueous solutions: osmotic second virial coefficient calculations using the MARTINI coarse-grained force field. AB - Coarse-grained (CG) simulation methods are now widely used to model the structure and dynamics of large biomolecular systems. One important issue for using such methods - especially with regard to using them to model, for example, intracellular environments - is to demonstrate that they can reproduce experimental data on the thermodynamics of protein-protein interactions in aqueous solutions. To examine this issue, we describe here simulations performed using the popular coarse-grained MARTINI force field, aimed at computing the thermodynamics of lysozyme and chymotrypsinogen self-interactions in aqueous solution. Using molecular dynamics simulations to compute potentials of mean force between a pair of protein molecules, we show that the original parameterization of the MARTINI force field is likely to significantly overestimate the strength of protein-protein interactions to the extent that the computed osmotic second virial coefficients are orders of magnitude more negative than experimental estimates. We then show that a simple down-scaling of the van der Waals parameters that describe the interactions between protein pseudo-atoms can bring the simulated thermodynamics into much closer agreement with experiment. Overall, the work shows that it is feasible to test explicit-solvent CG force fields directly against thermodynamic data for proteins in aqueous solutions, and highlights the potential usefulness of osmotic second virial coefficient measurements for fully parameterizing such force fields. PMID- 24223530 TI - Recent Violence Among Persons Entering Short-Term Residential Mental Health and Substance Abuse Treatment. AB - OBJECTIVE: Large-scale epidemiologic studies have consistently found that co occurring mental and substance use disorders are associated with increased risk of involvement in violence. Individuals with co-occurring mental and substance use disorders can present either in mental health or substance abuse treatment systems, and both systems must be able to respond to their needs. This study examined the prevalence and correlates of recent violence (both perpetration and victimization) among adults (N=419) entering short-term residential mental health and substance abuse treatment. METHODS: Approximately 41% (n=171) of participants reported having any involvement in violence, and for the majority of them (n=144; 84%) that included victimization. For analytic purposes, we classified participants with involvement in violence as any perpetration (n=87) or only victimization (n=84), and conducted bivariate and multivariate logistic regression analyses examining potential correlates of these different types of violence. RESULTS: Homelessness (AOR= 1.6, 95% CI[1.0-2.4], p<.04), alcohol use disorder (AOR=1.8, 95% CI[1.1-2.9], p<.03), and the interaction of comorbidity and substance abuse treatment system (AOR=2.8, 95% CI[1.0-7.6], p<.05) were associated with an increased likelihood of any violence. Alcohol use disorder (AOR=1.8, 95% CI[1.0-3.3], p<.05) increased the likelihood of perpetration. Homelessness (AOR=1.9, 95% CI[1.1-3.2], p<.02) and the interaction of comorbidity and being recruited from substance abuse treatment (AOR=5.1, 95% CI[1.8-14.2], p<.003) increased the likelihood of involvement in only victimization. CONCLUSIONS: Victimization was far more prevalent than perpetration. Comorbidity was not a significant predictor of violence, but comorbid individuals recruited from the substance abuse treatment system were more likely to be involved in violence. PMID- 24223531 TI - The Addiction Psychiatrist as Dual Diagnosis Physician: A Profession in Great Need and Greatly Needed. AB - Addiction is the number one cause of premature illness and death in the U.S., especially among people with mental illness. Yet American medicine lacks sufficient workforce capacity, expertise, training, infrastructure, and research to support treatment for people with co-occurring addictions and mental illness. This essay argues that the addiction psychiatrist is essential in dual diagnosis care. PMID- 24223532 TI - Comorbid Alcohol Dependence and Anxiety Disorders: A National Survey. AB - OBJECTIVE: The goal of this study was to describe onset of comorbid anxiety disorders and alcohol dependence based on a large national survey of the US adult population, and to explore and describe these patterns by gender. METHODS: Using Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) data, we compared age of onset and temporal ordering of onset of comorbid alcohol dependence and anxiety disorders. Analyses were stratified by gender. Mean ages of onset were calculated, and Wald F-tests were used to assess differences in ages of onset, accounting for the complex survey design of the NESARC. Weighted estimates were used, adjusted to be representative of the US population on various sociodemographic variables based on the 2000 Decennial Census. RESULTS: Differences in temporal ordering were observed, but varied by disorder combination. The majority (65%) had a primary (earliest onset) anxiety disorder, while the remaining 35% had a primary alcohol dependence diagnosis. Age of onset for some individuals with an anxiety disorder comorbid with alcohol dependence was earlier than for those with an anxiety disorder alone. Among individuals with comorbid social phobia and alcohol dependence, and comorbid specific phobia and alcohol dependence, it was more common to experience anxiety disorder as the primary diagnosis. Conversely, among individuals with comorbid panic disorder and alcohol dependence, and generalized anxiety disorder and alcohol dependence, it was more common to experience alcohol dependence as the primary diagnosis. Women were more likely to report having multiple comorbid anxiety disorders. No gender differences were found in terms of age of onset or temporal ordering of onset of comorbid disorders. CONCLUSIONS: Subsets of individuals with comorbid disorders exist, some whose primary diagnosis is alcohol dependence, and a majority of individuals whose primary diagnosis is an anxiety disorder with significant variability in age and temporal ordering of onset and few gender differences. Improved understanding of patterns of comorbidity and lag time between the onsets of specific disorders may enable us to identify potential groups for early intervention. PMID- 24223533 TI - Classification of Small Lesions in Breast MRI: Evaluating The Role of Dynamically Extracted Texture Features Through Feature Selection. AB - Dynamic texture quantification, i.e., extracting texture features from the lesion enhancement pattern in all available post-contrast images, has not been evaluated in terms of its ability to classify small lesions. This study investigates the classification performance achieved with texture features extracted from all five post-contrast images of lesions (mean lesion diameter of 1.1 cm) annotated in dynamic breast magnetic resonance imaging exams. Sixty lesions are characterized dynamically using Haralick texture features. The texture features are then used in a classification task with support vector regression and a fuzzy k-nearest neighbor classifier; free parameters of these classifiers are optimized using random sub-sampling cross-validation. Classifier performance is determined through receiver-operator characteristic (ROC) analysis, specifically through computation of the area under the ROC curve (AUC). Mutual information is used to evaluate the contribution of texture features extracted from different post contrast stages to classifier performance. Significant improvements (p < 0.05) are observed for six of the thirteen texture features when the lesion enhancement pattern is quantified using the proposed approach of dynamic texture quantification. The highest AUC value observed (0.82) is achieved with texture features responsible for capturing aspects of lesion heterogeneity. Mutual information analysis reveals that texture features extracted from the third and fourth post-contrast images contributed most to the observed improvement in classifier performance. These results show that the performance of automated character classification with small lesions can be significantly improved through dynamic texture quantification of the lesion enhancement pattern. PMID- 24223534 TI - Characterization of bladder sensory neurons in the context of myelination, receptors for pain modulators, and acute responses to bladder inflammation. AB - Bladder sensation is mediated by lumbosacral dorsal root ganglion neurons and is essential for normal voiding and nociception. Numerous electrophysiological, structural, and molecular changes occur in these neurons following inflammation. Defining which neurons undergo these changes is critical for understanding the mechanism underlying bladder pain and dysfunction. Our first aim was to define the chemical classes of bladder sensory neurons that express receptors for the endogenous modulators of nociceptor sensitivity, glial cell line-derived neurotrophic factor (GDNF), the related neurotrophic factor, artemin, and estrogens. Bladder sensory neurons of adult female Sprague-Dawley rats were identified with retrograde tracer. Diverse groups of neurons express these receptors, and some neurons express receptors for both neurotrophic factors and estrogens. Lumbar and sacral sensory neurons showed some distinct differences in their expression profile. We also distinguished the chemical profile of myelinated and unmyelinated bladder sensory neurons. Our second aim was to identify bladder sensory neurons likely to be undergoing structural remodeling during inflammation. Following systemic administration of cyclophosphamide (CYP), its renal metabolite acrolein causes transient urothelial loss, exposing local afferent terminals to a toxic environment. CYP induced expression of the injury related immediate-early gene product, activating transcription factor-3 (ATF-3), in a small population of sacral nitrergic bladder sensory neurons. In conclusion, we have defined the bladder sensory neurons that express receptors for GDNF, artemin and estrogens. Our study has also identified a sub-population of sacral sensory neurons that are likely to be undergoing structural remodeling during acute inflammation of the bladder. Together these results contribute to increased understanding of the neurons that are known to be involved in pain modulation and hyperreflexia during inflammation. PMID- 24223535 TI - Intersection of effort and risk: ethological and neurobiological perspectives. AB - The physical effort required to seek out and extract a resource is an important consideration for a foraging animal. A second consideration is the variability or risk associated with resource delivery. An intriguing observation from ethological studies is that animals shift their preference from stable to variable food sources under conditions of increased physical effort or falling energetic reserves. Although theoretical models for this effect exist, no exploration into its biological basis has been pursued. Recent advances in understanding the neural basis of effort- and risk-guided decision making suggest that opportunities exist for determining how effort influences risk preference. In this review, we describe the intersection between the neural systems involved in effort- and risk-guided decision making and outline two mechanisms by which effort-induced changes in dopamine release may increase the preference for variable rewards. PMID- 24223537 TI - Novel ncRNAs transcribed by Pol III and elucidation of their functional relevance by biophysical approaches. AB - In the last decade the role of non coding (nc) RNAs in neurogenesis and in the onset of neurological diseases has been assessed by a multitude of studies. In this scenario, approximately 30 small RNA polymerase (pol) III-dependent ncRNAs were recently identified by computational tools and proposed as regulatory elements. The function of several of these transcripts was elucidated in vitro and in vivo confirming their involvement in cancer and in metabolic and neurodegenerative disorders. Emerging biophysical technologies together with the introduction of a physical perspective have been advantageous in regulatory RNA investigation providing original results on: (a) the differentiation of neuroblastoma (NB) cells towards a neuron-like phenotype triggered by Neuroblastoma Differentiation Marker 29 (NDM29) ncRNA; (b) the modulation of A type K(+) current in neurons induced by the small ncRNA 38A and (c) the synthesis driven by 17A ncRNA of a GABAB2 receptor isoform unable to trigger intracellular signaling. Moreover, the application of Single Cell Force Spectroscopy (SCFS) to these studies suggests a correlation between the malignancy stage of NB and the micro-adhesive properties of the cells, allowing to investigate the molecular basis of such a correlation. PMID- 24223536 TI - Wnts in action: from synapse formation to synaptic maintenance. AB - A proper balance between synapse assembly and disassembly is crucial for the formation of functional neuronal circuits and synaptic plasticity in the adult brain. During development, synaptogenesis generates a vast excess of synapses, which are subsequently eliminated. Importantly, aberrant synaptic disassembly during development underpins many neurological disorders. Wnt secreted proteins are robust synaptogenic factors that regulate synapse assembly and function in the developing and mature brain. Recent studies show that Wnt blockade with the antagonist Dickkopf-1 (Dkk1) induces the rapid disassembly of synapses in mature neurons. Importantly, Dkk1 mediates synaptic loss induced by Amyloid-beta, a key pathogenic molecule in Alzheimer's disease (AD). These findings provide new insights into the potential contribution of dysfunctional Wnt signaling to synaptic loss observed in neurodegenerative diseases. In this review, we discuss the role of Wnt signaling in vertebrate synaptic assembly, function and maintenance, and consider how dysfunction of Wnt signaling could contribute to synaptic disassembly in neurodegenerative diseases such as AD. PMID- 24223538 TI - Global actions of nicotine on the striatal microcircuit. AB - THE QUESTION TO SOLVE IN THE PRESENT WORK IS: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA. PMID- 24223539 TI - Odors enhance the salience of matching images during the attentional blink. AB - As any food critic knows, the visual presentation of a dish can enhance its aroma. Is the reverse also true? Here we investigated whether odors can enhance the salience of familiar visual objects at the limits of perceptual discrimination, using rapid serial visual presentations (RSVP) to induce an attentional blink (AB). We had participants view RSVP streams containing photographs of odor-related objects (lemon, orange, rose, and mint) amongst non odor related distractors. In each trial, participants inhaled a single odor, which either matched the odor-related target within the stream (congruent trials), did not match the odor-related target (incongruent trials), or was irrelevant with respect to the target. Congruent odors significantly attenuated the AB for odor-related visual targets, compared with incongruent and irrelevant odors. The findings suggest that familiar odors can render matching visual objects more salient, thereby enhancing their competitive strength at the limits of temporal attention. PMID- 24223540 TI - Neural activity tied to reading predicts individual differences in extended-text comprehension. AB - Reading comprehension depends on neural processes supporting the access, understanding, and storage of words over time. Examinations of the neural activity correlated with reading have contributed to our understanding of reading comprehension, especially for the comprehension of sentences and short passages. However, the neural activity associated with comprehending an extended text is not well-understood. Here we describe a current-source-density (CSD) index that predicts individual differences in the comprehension of an extended text. The index is the difference in CSD-transformed event-related potentials (ERPs) to a target word between two conditions: a comprehension condition with words from a story presented in their original order, and a scrambled condition with the same words presented in a randomized order. In both conditions participants responded to the target word, and in the comprehension condition they also tried to follow the story in preparation for a comprehension test. We reasoned that the spatiotemporal pattern of difference-CSDs would reflect comprehension-related processes beyond word-level processing. We used a pattern-classification method to identify the component of the difference-CSDs that accurately (88%) discriminated good from poor comprehenders. The critical CSD index was focused at a frontal-midline scalp site, occurred 400-500 ms after target-word onset, and was strongly correlated with comprehension performance. Behavioral data indicated that group differences in effort or motor preparation could not explain these results. Further, our CSD index appears to be distinct from the well-known P300 and N400 components, and CSD transformation seems to be crucial for distinguishing good from poor comprehenders using our experimental paradigm. Once our CSD index is fully characterized, this neural signature of individual differences in extended-text comprehension may aid the diagnosis and remediation of reading comprehension deficits. PMID- 24223541 TI - The eye-voice lead during oral reading in developmental dyslexia. AB - In reading aloud, the eye typically leads over voice position. In the present study, eye movements and voice utterances were simultaneously recorded and tracked during the reading of a meaningful text to evaluate the eye-voice lead in 16 dyslexic and 16 same-age control readers. Dyslexic children were slower than control peers in reading texts. Their slowness was characterized by a great number of silent pauses and sounding-out behaviors and a small lengthening of word articulation times. Regarding eye movements, dyslexic readers made many more eye fixations (and generally smaller rightward saccades) than controls. Eye movements and voice (which were shifted in time because of the eye-voice lead) were synchronized in dyslexic readers as well as controls. As expected, the eye voice lead was significantly smaller in dyslexic than control readers, confirming early observations by Buswell (1921) and Fairbanks (1937). The eye-voice lead was significantly correlated with several eye movements and voice parameters, particularly number of fixations and silent pauses. The difference in performance between dyslexic and control readers across several eye and voice parameters was expressed by a ratio of about 2. We propose that referring to proportional differences allows for a parsimonious interpretation of the reading deficit in terms of a single deficit in word decoding. The possible source of this deficit may call for visual or phonological mechanisms, including Goswami's temporal sampling framework. PMID- 24223542 TI - Reporting dream experience: Why (not) to be skeptical about dream reports. AB - Are dreams subjective experiences during sleep? Is it like something to dream, or is it only like something to remember dreams after awakening? Specifically, can dream reports be trusted to reveal what it is like to dream, and should they count as evidence for saying that dreams are conscious experiences at all? The goal of this article is to investigate the relationship between dreaming, dream reporting and subjective experience during sleep. I discuss different variants of philosophical skepticism about dream reporting and argue that they all fail. Consequently, skeptical doubts about the trustworthiness of dream reports are misguided, and for systematic reasons. I suggest an alternative, anti-skeptical account of the trustworthiness of dream reports. On this view, dream reports, when gathered under ideal reporting conditions and according to the principle of temporal proximity, are trustworthy (or transparent) with respect to conscious experience during sleep. The transparency assumption has the status of a methodologically necessary default assumption and is theoretically justified because it provides the best explanation of dream reporting. At the same time, it inherits important insights from the discussed variants of skepticism about dream reporting, suggesting that the careful consideration of these skeptical arguments ultimately leads to a positive account of why and under which conditions dream reports can and should be trusted. In this way, moderate distrust can be fruitfully combined with anti-skepticism about dream reporting. Several perspectives for future dream research and for the comparative study of dreaming and waking experience are suggested. PMID- 24223543 TI - On the physiology of jouissance: interpreting the mesolimbic dopaminergic reward functions from a psychoanalytic perspective. AB - Jouissance is a Lacanian concept, infamous for being impervious to understanding and which expresses the paradoxical satisfaction that a subject may derive from his symptom. On the basis of Freud's "experience of satisfaction" we have proposed a first working definition of jouissance as the (benefit gained from) the motor tension underlying the action which was [once] adequate in bringing relief to the drive and, on the basis of their striking reciprocal resonances, we have proposed that central dopaminergic systems could embody the physiological architecture of Freud's concept of the drive. We have then distinguished two constitutive axes to jouissance: one concerns the subject's body and the other the subject's history. Four distinctive aspects of these axes are discussed both from a metapsychological and from a neuroscience point of view. We conclude that jouissance could be described as an accumulation of body tension, fuelling for action, but continuously balancing between reward and anxiety, and both marking the physiology of the body with the history of its commemoration and arising from this inscription as a constant push to act and to repeat. Moreover, it seems that the mesolimbic accumbens dopaminergic pathway is a reasonable candidate for its underlying physiological architecture. PMID- 24223544 TI - Converging Pathways in Autism Spectrum Disorders: Interplay between Synaptic Dysfunction and Immune Responses. AB - Autism spectrum disorders (ASD) are highly heritable, yet genetically heterogeneous neurodevelopmental conditions. Recent genome-wide association and gene expression studies have provided evidence supporting the notion that the large number of genetic variants associated with ASD converge toward a core set of dysregulated biological processes. Here we review recent data demonstrating the involvement of synaptic dysfunction and abnormal immune responses in ASD, and discuss the functional interplay between the two phenomena. PMID- 24223545 TI - The balanced mind: the variability of task-unrelated thoughts predicts error monitoring. AB - Self-generated thoughts unrelated to ongoing activities, also known as "mind wandering," make up a substantial portion of our daily lives. Reports of such task-unrelated thoughts (TUTs) predict both poor performance on demanding cognitive tasks and blood-oxygen-level-dependent (BOLD) activity in the default mode network (DMN). However, recent findings suggest that TUTs and the DMN can also facilitate metacognitive abilities and related behaviors. To further understand these relationships, we examined the influence of subjective intensity, ruminative quality, and variability of mind-wandering on response inhibition and monitoring, using the Error Awareness Task (EAT). We expected to replicate links between TUT and reduced inhibition, and explored whether variance in TUT would predict improved error monitoring, reflecting a capacity to balance between internal and external cognition. By analyzing BOLD responses to subjective probes and the EAT, we dissociated contributions of the DMN, executive, and salience networks to task performance. While both response inhibition and online TUT ratings modulated BOLD activity in the medial prefrontal cortex (mPFC) of the DMN, the former recruited a more dorsal area implying functional segregation. We further found that individual differences in mean TUTs strongly predicted EAT stop accuracy, while TUT variability specifically predicted levels of error awareness. Interestingly, we also observed co-activation of salience and default mode regions during error awareness, supporting a link between monitoring and TUTs. Altogether our results suggest that although TUT is detrimental to task performance, fluctuations in attention between self-generated and external task-related thought is a characteristic of individuals with greater metacognitive monitoring capacity. Achieving a balance between internally and externally oriented thought may thus aid individuals in optimizing their task performance. PMID- 24223547 TI - Increased hippocampal volume and gene expression following cognitive behavioral therapy in PTSD. PMID- 24223548 TI - Perspectives for computational modeling of cell replacement for neurological disorders. AB - Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects. PMID- 24223546 TI - Emotion regulation, attention to emotion, and the ventral attentional network. AB - ACCOUNTS OF THE EFFECT OF EMOTIONAL INFORMATION ON BEHAVIORAL RESPONSE AND CURRENT MODELS OF EMOTION REGULATION ARE BASED ON TWO OPPOSED BUT INTERACTING PROCESSES: automatic bottom-up processes (triggered by emotionally arousing stimuli) and top-down control processes (mapped to prefrontal cortical areas). Data on the existence of a third attentional network operating without recourse to limited-capacity processes but influencing response raise the issue of how it is integrated in emotion regulation. We summarize here data from attention to emotion, voluntary emotion regulation, and on the origin of biases against negative content suggesting that the ventral network is modulated by exposure to emotional stimuli when the task does not constrain the handling of emotional content. In the parietal lobes, preferential activation of ventral areas associated with "bottom-up" attention by ventral network theorists is strongest in studies of cognitive reappraisal. In conditions when no explicit instruction is given to change one's response to emotional stimuli, control of emotionally arousing stimuli is observed without concomitant activation of the dorsal attentional network, replaced by a shift of activation toward ventral areas. In contrast, in studies where emotional stimuli are placed in the role of distracter, the observed deactivation of these ventral semantic association areas is consistent with the existence of proactive control on the role emotional representations are allowed to take in generating response. It is here argued that attentional orienting mechanisms located in the ventral network constitute an intermediate kind of process, with features only partially in common with effortful and automatic processes, which plays an important role in handling emotion by conveying the influence of semantic networks, with which the ventral network is co-localized. Current neuroimaging work in emotion regulation has neglected this system by focusing on a bottom-up/top-down dichotomy of attentional control. PMID- 24223549 TI - Temporal binding of sound emerges out of anatomical structure and synaptic dynamics of auditory cortex. AB - The ability to represent and recognize naturally occuring sounds such as speech depends not only on spectral analysis carried out by the subcortical auditory system but also on the ability of the cortex to bind spectral information over time. In primates, these temporal binding processes are mirrored as selective responsiveness of neurons to species-specific vocalizations. Here, we used computational modeling of auditory cortex to investigate how selectivity to spectrally and temporally complex stimuli is achieved. A set of 208 microcolumns were arranged in a serial core-belt-parabelt structure documented in both humans and animals. Stimulus material comprised multiple consonant-vowel (CV) pseudowords. Selectivity to the spectral structure of the sounds was commonly found in all regions of the model (N = 122 columns out of 208), and this selectivity was only weakly affected by manipulating the structure and dynamics of the model. In contrast, temporal binding was rarer (N = 39), found mostly in the belt and parabelt regions. Thus, the serial core-belt-parabelt structure of auditory cortex is necessary for temporal binding. Further, adaptation due to synaptic depression-rendering the cortical network malleable by stimulus history was crucial for the emergence of neurons sensitive to the temporal structure of the stimuli. Both spectral selectivity and temporal binding required that a sufficient proportion of the columns interacted in an inhibitory manner. The model and its structural modifications had a small-world structure (i.e., columns formed clusters and were within short node-to-node distances from each other). However, simulations showed that a small-world structure is not a necessary condition for spectral selectivity and temporal binding to emerge. In summary, this study suggests that temporal binding arises out of (1) the serial structure typical to the auditory cortex, (2) synaptic adaptation, and (3) inhibitory interactions between microcolumns. PMID- 24223550 TI - Simultaneous stability and sensitivity in model cortical networks is achieved through anti-correlations between the in- and out-degree of connectivity. AB - Neuronal networks in rodent barrel cortex are characterized by stable low baseline firing rates. However, they are sensitive to the action potentials of single neurons as suggested by recent single-cell stimulation experiments that reported quantifiable behavioral responses in response to short spike trains elicited in single neurons. Hence, these networks are stable against internally generated fluctuations in firing rate but at the same time remain sensitive to similarly-sized externally induced perturbations. We investigated stability and sensitivity in a simple recurrent network of stochastic binary neurons and determined numerically the effects of correlation between the number of afferent ("in-degree") and efferent ("out-degree") connections in neurons. The key advance reported in this work is that anti-correlation between in-/out-degree distributions increased the stability of the network in comparison to networks with no correlation or positive correlations, while being able to achieve the same level of sensitivity. The experimental characterization of degree distributions is difficult because all pre-synaptic and post-synaptic neurons have to be identified and counted. We explored whether the statistics of network motifs, which requires the characterization of connections between small subsets of neurons, could be used to detect evidence for degree anti-correlations. We find that the sample frequency of the 3-neuron "ring" motif (1->2->3->1), can be used to detect degree anti-correlation for sub-networks of size 30 using about 50 samples, which is of significance because the necessary measurements are achievable experimentally in the near future. Taken together, we hypothesize that barrel cortex networks exhibit degree anti-correlations and specific network motif statistics. PMID- 24223551 TI - Northwestern University Schizophrenia Data and Software Tool (NUSDAST). AB - The schizophrenia research community has invested substantial resources on collecting, managing and sharing large neuroimaging datasets. As part of this effort, our group has collected high resolution magnetic resonance (MR) datasets from individuals with schizophrenia, their non-psychotic siblings, healthy controls and their siblings. This effort has resulted in a growing resource, the Northwestern University Schizophrenia Data and Software Tool (NUSDAST), an NIH funded data sharing project to stimulate new research. This resource resides on XNAT Central, and it contains neuroimaging (MR scans, landmarks and surface maps for deep subcortical structures, and FreeSurfer cortical parcellation and measurement data), cognitive (cognitive domain scores for crystallized intelligence, working memory, episodic memory, and executive function), clinical (demographic, sibling relationship, SAPS and SANS psychopathology), and genetic (20 polymorphisms) data, collected from more than 450 subjects, most with 2-year longitudinal follow-up. A neuroimaging mapping, analysis and visualization software tool, CAWorks, is also part of this resource. Moreover, in making our existing neuroimaging data along with the associated meta-data and computational tools publically accessible, we have established a web-based information retrieval portal that allows the user to efficiently search the collection. This research-ready dataset meaningfully combines neuroimaging data with other relevant information, and it can be used to help facilitate advancing neuroimaging research. It is our hope that this effort will help to overcome some of the commonly recognized technical barriers in advancing neuroimaging research such as lack of local organization and standard descriptions. PMID- 24223552 TI - Robust active binocular vision through intrinsically motivated learning. AB - The efficient coding hypothesis posits that sensory systems of animals strive to encode sensory signals efficiently by taking into account the redundancies in them. This principle has been very successful in explaining response properties of visual sensory neurons as adaptations to the statistics of natural images. Recently, we have begun to extend the efficient coding hypothesis to active perception through a form of intrinsically motivated learning: a sensory model learns an efficient code for the sensory signals while a reinforcement learner generates movements of the sense organs to improve the encoding of the signals. To this end, it receives an intrinsically generated reinforcement signal indicating how well the sensory model encodes the data. This approach has been tested in the context of binocular vison, leading to the autonomous development of disparity tuning and vergence control. Here we systematically investigate the robustness of the new approach in the context of a binocular vision system implemented on a robot. Robustness is an important aspect that reflects the ability of the system to deal with unmodeled disturbances or events, such as insults to the system that displace the stereo cameras. To demonstrate the robustness of our method and its ability to self-calibrate, we introduce various perturbations and test if and how the system recovers from them. We find that (1) the system can fully recover from a perturbation that can be compensated through the system's motor degrees of freedom, (2) performance degrades gracefully if the system cannot use its motor degrees of freedom to compensate for the perturbation, and (3) recovery from a perturbation is improved if both the sensory encoding and the behavior policy can adapt to the perturbation. Overall, this work demonstrates that our intrinsically motivated learning approach for efficient coding in active perception gives rise to a self-calibrating perceptual system of high robustness. PMID- 24223553 TI - Characterization of affective states by pupillary dynamics and autonomic correlates. AB - With the recent advent of new recording devices and an easier access to signal processing tools, researchers are increasingly exploring and studying the Pupil Dilation (PD) signal. Recently, numerous studies pointed out the relations between PD dynamics and psychophysiological states. Although it is well known that PD is controlled by the Autonomic Nervous System (ANS), and ANS responses are related to emotional events/stimuli, the relationship between emotional states and PD is still an open issue. The aim of this study is to define the statistical properties of the PD signal, to understand its relation with ANS correlates such as Heart Rate Variability (HRV) and respiration (RESP), and to explore if PD could provide information for the evaluation of the psychophysiological response of ANS to affective triggering events. ECG, RESP, and PD data from 13 normal subjects were recorded during a memory recall paradigm, and processed with spectral and cross-spectral analysis. Our results demonstrate that variability indices extracted from fast PD oscillations, not observable through standard cardiorespiratory identification in the frequency domain, would be able to discern psychophysiological responses elicited by basic emotional stimuli. A strong linear coupling was found between the variables, due to the influence of RESP on both PD and HRV within the High Frequency (HF) band, from 0.15 to 0.45 Hz. Most importantly, our results point at PD features as possible candidates for characterizing basic emotional stimuli. PMID- 24223554 TI - Blood-brain transfer of Pittsburgh compound B in humans. AB - In the labeled form, the Pittsburgh compound B (2-(4'-{N-methyl-[(11)C]}methyl aminophenyl)-6-hydroxy-benzothiazole, [(11)C]PiB), is used as a biomarker for positron emission tomography (PET) of brain beta-amyloid deposition in Alzheimer's disease (AD). The permeability of [(11)C]PiB in the blood-brain barrier is held to be high but the permeability-surface area product and extraction fractions in patients or healthy volunteers are not known. We used PET to determine the clearance associated with the unidrectional blood-brain transfer of [(11)C]PiB and the corresponding cerebral blood flow rates in frontal lobe, whole cerebral cortex, and cerebellum of patients with Alzheimer's disease and healthy volunteers. Regional cerebral blood flow rates differed significantly between the two groups. Thus, regional and whole-brain permeability-surface area products were identical, in agreement with the observation that numerically, but insignificantly, unidirectional blood-brain clearances are lower and extraction fractions higher in the patients. The evidence of unchanged permeability-surface area products in the patients implies that blood flow changes can be deduced from the unidirectional blood-brain clearances of [(11)C]PiB in the patients. PMID- 24223555 TI - Accumulation of MRI Markers of Cerebral Small Vessel Disease is Associated with Decreased Cognitive Function. A Study in First-Ever Lacunar Stroke and Hypertensive Patients. AB - BACKGROUND: White matter lesions (WMLs), asymptomatic lacunar infarcts, brain microbleeds (BMBs), and enlarged perivascular spaces (EPVS) have been identified as silent lesions due to cerebral small vessel disease (cSVD). All these markers have been individually linked to cognitive functioning, but are also strongly correlated with each other. The combined effect of these markers on cognitive function has never been studied and would possibly provide more useful information on the effect on cognitive function. METHODS: Brain MRI and extensive neuropsychological assessment were performed in 189 patients at risk for cSVD (112 hypertensive patients and 77 first-ever lacunar stroke patients). We rated the presence of any asymptomatic lacunar infarct, extensive WMLs, any deep BMB, and moderate to extensive EPVS in the basal ganglia. The presence of each marker was summed to an ordinal score between 0 and 4. Associations with domains of cognitive function (memory, executive function, information processing speed, and overall cognition) were analyzed with correlation analyses. RESULTS: Correlation analyses revealed significant associations between accumulating cSVD burden and decreased performance on all cognitive domains (all p <= 0.001). RESULTS remained significant for information processing speed (r = -0.181, p = 0.013) and overall cognition (r = -0.178, p = 0.017), after correction for age and sex. Testing of trend using linear regression analyses revealed the same results. DISCUSSION: We tested a new approach to capture total brain damage resulting from cSVD and found that accumulation of MRI burden of cSVD is associated with decreased performance on tests of information processing speed and overall cognition, implying that accumulating brain damage is accompanied by worse cognitive functioning. PMID- 24223556 TI - Missing signposts on the roadmap to quality: a call to improve medication adherence indicators in data collection for population research. AB - PURPOSE: Poor adherence to prescribed medicines is associated with increased rates of poor outcomes, including hospitalization, serious adverse events, and death, and is also associated with increased healthcare costs. However, current approaches to evaluation of medication adherence using real-world electronic health records (EHRs) or claims data may miss critical opportunities for data capture and fall short in modeling and representing the full complexity of the healthcare environment. We sought to explore a framework for understanding and improving data capture for medication adherence in a population-based intervention in four U.S. counties. APPROACH: We posited that application of a data model and a process matrix when designing data collection for medication adherence would improve identification of variables and data accessibility, and could support future research on medication-taking behaviors. We then constructed a use case in which data related to medication adherence would be leveraged to support improved healthcare quality, clinical outcomes, and efficiency of healthcare delivery in a population-based intervention for persons with diabetes. Because EHRs in use at participating sites were deemed incapable of supplying the needed data, we applied a taxonomic approach to identify and define variables of interest. We then applied a process matrix methodology, in which we identified key research goals and chose optimal data domains and their respective data elements, to instantiate the resulting data model. CONCLUSIONS: Combining a taxonomic approach with a process matrix methodology may afford significant benefits when designing data collection for clinical and population-based research in the arena of medication adherence. Such an approach can effectively depict complex real-world concepts and domains by "mapping" the relationships between disparate contributors to medication adherence and describing their relative contributions to the shared goals of improved healthcare quality, outcomes, and cost. PMID- 24223558 TI - The N-terminal cytoplasmic region of NCBE displays features of an intrinsic disordered structure and represents a novel target for specific drug screening. AB - The sodium dependent bicarbonate transporter NCBE/NBCn2 is predominantly expressed in the central nervous system (CNS). The highest protein concentrations are found in the choroid plexus. The primary function of this integral plasma membrane transport protein is to regulate intracellular neuronal pH and also probably to maintain the pH homeostasis across the blood-cerebrospinal fluid barrier. NCBE is predicted to contain at least 10 transmembrane helices. The N- and C- termini are both cytoplasmic, with a large N-terminal domain (Nt-NCBE) and a relatively small C-terminal domain (Ct-NCBE). The Nt-NCBE is likely to be involved in bicarbonate recognition and transport and contains key areas of regulation involving pH sensing and protein-protein interactions. Intrinsic disordered protein regions (IDPRs) are defined as protein regions having no rigid three-dimensional structure under physiological conditions. They are believed to be involved in signaling networks in which specific, low affinity, protein protein interactions play an important role. We predict that NCBE and other SoLute Carrier 4 (SLC4) family members have a high level of intrinsic disorder in their cytoplasmic regions. To provide biophysical evidence for the IDPRs predicted in Nt-NCBE, we produced pure (>99%), recombinant Nt-NCBE using E. coli as the expression host. The protein was used to perform differential scanning fluorescence spectroscopy (DSF), in order to search for small molecules that would induce secondary or tertiary structure in the IDPRs. We expect this to assist the development of selective pharmaceutical compounds against individual SLC4 family members. We have also determined a low resolution (4 A) X-ray crystal structure of the N-terminal core domain. The N-terminal cytoplasmic domain (cdb3) of anion exchanger 1 (AE1) shares a similar fold with the N-terminal core domain of NCBE. Crystallization conditions for the full-length N-terminal domain have been sought, but only the core domain yields diffracting crystals. PMID- 24223557 TI - Cardiovascular reactivity, stress, and physical activity. AB - Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD). Acute mental stress can activate the sympathetic adrenal-medullary (SAM) axis, eliciting the release of catecholamines (NE and EPI) resulting in the elevation of heart rate (HR) and blood pressure (BP). Combined stress (psychological and physical) can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement). Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR) reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time) in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD. PMID- 24223560 TI - Statistics on cannabis users skew perceptions of cannabis use. AB - Collecting information about the prevalence of cannabis use is necessary but not sufficient for understanding the size, dynamics, and outcomes associated with cannabis markets. This paper uses two data sets describing cannabis consumption in the United States and Europe to highlight (1) differences in inferences about sub-populations based on the measure used to quantify cannabis-related activity; (2) how different measures of cannabis-related activity can be used to more accurately describe trends in cannabis usage over time; and (3) the correlation between frequency of use in the past-month and average grams consumed per use day. KEY FINDINGS: focusing on days of use instead of prevalence shows substantially greater increases in U.S. cannabis use in recent years; however, the recent increase is mostly among adults, not youth. Relatively more rapid growth in use days also occurred among the college-educated and Hispanics. Further, data from a survey conducted in seven European countries show a strong positive correlation between frequency of use and quantity consumed per day of use, suggesting consumption is even more skewed toward the minority of heavy users than is suggested by days-of-use calculations. PMID- 24223559 TI - Adrenoreceptors and nitric oxide in the cardiovascular system. AB - Nitric Oxide (NO) is a small molecule that continues to attract much attention from the scientific community. Since its discovery, it has been evident that NO has a crucial role in the modulation of vascular tone. Moreover, NO is involved in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. NO effects can be either dependent or independent on cGMP, and rely also upon several mechanisms such as the amount of NO, the compartmentalization of the enzymes responsible for its biosynthesis (NOS), and the local redox conditions. Several evidences highlighted the correlation among adrenoreceptors activity, vascular redox status and NO bioavailability. It was suggested a possible crosstalk between NO and oxidative stress hallmarks in the endothelium function and adaptation, and in sympathetic vasoconstriction control. Adrenergic vasoconstriction is a balance between a direct vasoconstrictive effect on smooth muscle and an indirect vasorelaxant action caused by alpha2- and beta adrenergic endothelial receptor-triggered NO release. An increased oxidative stress and a reduction of NO bioavailability shifts this equilibrium causing the enhanced vascular adrenergic responsiveness observed in hypertension. The activity of NOS contributes to manage the adrenergic pathway, thus supporting the idea that the endothelium might control or facilitate beta-adrenergic effects on the vessels and the polymorphic variants in beta2-receptors and NOS isoforms could influence aging, some pathological conditions and individual responses to drugs. This seems to be dependent, almost in part, on differences in the control of vascular tone exerted by NO. Given its involvement in such important mechanisms, the NO pathway is implicated in aging process and in both cardiovascular and non-cardiovascular conditions. Thus, it is essential to pinpoint NO involvement in the regulation of vascular tone for the effective clinical/therapeutic management of cardiovascular diseases (CVD). PMID- 24223561 TI - Mirror-touch and ticker tape experiences in synesthesia. AB - A fundamental question in the field of synesthesia is whether it is associated with other cognitive phenomena. The current study examined synesthesia's connections with phenomenal traits of mirror-touch and ticker tape experiences, as well as the representation of the three phenomena in the population, across gender and domain of work/study. Mirror-touch is the automatic, involuntary experience of tactile sensation on one's own body when others are being touched. For example, seeing another person's arm being stroked can evoke physical touch sensation on one's own arm. Ticker tape is the automatic visualization of spoken words or thoughts, such as a teleprompter. For example, when spoken to, a ticker taper might see mentally the spoken words displayed in front of his face or as coming out of the speaker's mouth. To explore synesthesia's associations with these phenomena, a diverse group (n = 3743) was systematically recruited from eight universities and one public museum in France to complete an online screening. Of the 1017 eligible respondents, synesthetes (across all subtypes) reported higher rates of mirror-touch and ticker tape than non-synesthetes, suggesting that synesthesia is associated with these phenomenal traits. However, effect sizes were small and we could not rule out that response bias influenced these associations. Mirror-touch and ticker tape were independent. No differences were found across gender or domain of work and study in prevalence of synesthesia, mirror-touch or ticker tape. The prevalence of ticker tape, unknown so far, was estimated at about 7%, an intermediate rate between estimates of grapheme-color (2-4%) and sequence-space synesthesia (9-14%). Within synesthesia, grapheme-personification, also called ordinal-linguistic personification (OLP) was the most common subtype and was estimated around 12%. Co-occurences of the different types of synesthesia were higher than chance, though at the level of small effect sizes. PMID- 24223562 TI - Expectations in culturally unfamiliar music: influences of proximal and distal cues and timbral characteristics. AB - Listeners' musical perception is influenced by cues that can be stored in short term memory (e.g., within the same musical piece) or long-term memory (e.g., based on one's own musical culture). The present study tested how these cues (referred to as, respectively, proximal and distal cues) influence the perception of music from an unfamiliar culture. Western listeners who were naive to Gamelan music judged completeness and coherence for newly constructed melodies in the Balinese gamelan tradition. In these melodies, we manipulated the final tone with three possibilities: the original gong tone, an in-scale tone replacement or an out-of-scale tone replacement. We also manipulated the musical timbre employed in Gamelan pieces. We hypothesized that novice listeners are sensitive to out-of scale changes, but not in-scale changes, and that this might be influenced by the more unfamiliar timbre created by Gamelan "sister" instruments whose harmonics beat with the harmonics of the other instrument, creating a timbrally "shimmering" sound. The results showed: (1) out-of-scale endings were judged less complete than original gong and in-scale endings; (2) for melodies played with "sister" instruments, in-scale endings were judged as less complete than original endings. Furthermore, melodies using the original scale tones were judged more coherent than melodies containing few or multiple tone replacements; melodies played on single instruments were judged more coherent than the same melodies played on sister instruments. Additionally, there is some indication of within session statistical learning, with expectations for the initially-novel materials developing during the course of the experiment. The data suggest the influence of both distal cues (e.g., previously unfamiliar timbres) and proximal cues (within the same sequence and over the experimental session) on the perception of melodies from other cultural systems based on unfamiliar tunings and scale systems. PMID- 24223563 TI - The acoustic and perceptual cues affecting melody segregation for listeners with a cochlear implant. AB - Our ability to listen selectively to single sound sources in complex auditory environments is termed "auditory stream segregation."This ability is affected by peripheral disorders such as hearing loss, as well as plasticity in central processing such as occurs with musical training. Brain plasticity induced by musical training can enhance the ability to segregate sound, leading to improvements in a variety of auditory abilities. The melody segregation ability of 12 cochlear-implant recipients was tested using a new method to determine the perceptual distance needed to segregate a simple 4-note melody from a background of interleaved random-pitch distractor notes. In experiment 1, participants rated the difficulty of segregating the melody from distracter notes. Four physical properties of the distracter notes were changed. In experiment 2, listeners were asked to rate the dissimilarity between melody patterns whose notes differed on the four physical properties simultaneously. Multidimensional scaling analysis transformed the dissimilarity ratings into perceptual distances. Regression between physical and perceptual cues then derived the minimal perceptual distance needed to segregate the melody. The most efficient streaming cue for CI users was loudness. For the normal hearing listeners without musical backgrounds, a greater difference on the perceptual dimension correlated to the temporal envelope is needed for stream segregation in CI users. No differences in streaming efficiency were found between the perceptual dimensions linked to the F0 and the spectral envelope. Combined with our previous results in normally-hearing musicians and non-musicians, the results show that differences in training as well as differences in peripheral auditory processing (hearing impairment and the use of a hearing device) influences the way that listeners use different acoustic cues for segregating interleaved musical streams. PMID- 24223565 TI - The conceptual/procedural distinction belongs to strategies, not tasks: A comment on Gabriel et al. (2013). PMID- 24223564 TI - Aging mind and brain: is implicit learning spared in healthy aging? AB - It is often held that although explicit learning declines in the course of normal aging, implicit learning is relatively preserved. Here we summarize research from our group which leads us to argue that some forms of implicit learning do decline with adult age. In particular, we propose that there are age-related declines in implicit learning of probabilistic sequential relationships that occur across the adult lifespan, and that they reflect, at least in part, age-related striatal dysfunction. We first review behavioral evidence supporting this age-related decline and then evidence from patient groups, genetics, and neuroimaging supporting this striatal dysfunction hypothesis. PMID- 24223566 TI - The history of reimbursements in neurology. AB - The Patient Protection and Affordable Care Act (PPACA) addresses consumer protection, employer-provided insurance coverage, as well as the government's role in providing health care access to the most vulnerable populations. Within the practice of neurology, the PPACA has the challenging goal of reconciling the needs of the growing elderly population with the financial barriers to costly yet available health care services. To bridge that gap, all health care professionals working in the field of neurology must reflect on the effect previous Medicare reimbursement policies have had on the current practice of neurology, and utilize lessons learned in recent years. The test of time will tell whether the PPACA will achieve the goal of decreasing in health care spending while ensuring quality universal healthcare services. PMID- 24223567 TI - Kinematic and neurophysiological consequences of an assisted-force-feedback brain machine interface training: a case study. AB - In a proof-of-principle prototypical demonstration we describe a new type of brain-machine interface (BMI) paradigm for upper limb motor-training. The proposed technique allows a fast contingent and proportionally modulated stimulation of afferent proprioceptive and motor output neural pathways using operant learning. Continuous and immediate assisted-feedback of force proportional to rolandic rhythm oscillations during actual movements was employed and illustrated with a single case experiment. One hemiplegic patient was trained for 2 weeks coupling somatosensory brain oscillations with force-field control during a robot-mediated center-out motor-task whose execution approaches movements of everyday life. The robot facilitated actual movements adding a modulated force directed to the target, thus providing a non-delayed proprioceptive feedback. Neuro-electric, kinematic, and motor-behavioral measures were recorded in pre- and post-assessments without force assistance. Patient's healthy arm was used as control since neither a placebo control was possible nor other control conditions. We observed a generalized and significant kinematic improvement in the affected arm and a spatial accuracy improvement in both arms, together with an increase and focalization of the somatosensory rhythm changes used to provide assisted-force-feedback. The interpretation of the neurophysiological and kinematic evidences reported here is strictly related to the repetition of the motor-task and the presence of the assisted-force-feedback. Results are described as systematic observations only, without firm conclusions about the effectiveness of the methodology. In this prototypical view, the design of appropriate control conditions is discussed. This study presents a novel operant-learning-based BMI-application for motor-training coupling brain oscillations and force feedback during an actual movement. PMID- 24223568 TI - Quality of residual neuromuscular control and functional deficits in patients with spinal cord injury. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVE: This study examined the relationship between motor control and clinical function outcomes after spinal cord injury (SCI). SETTING: University of Louisville, Louisville, KY, USA. MATERIALS: Eleven persons with SCI and 5 non-injured subjects were included in this study. METHODS: The ASIA Impairment Scale (AIS) was used to categorize injury level and severity. Multi-muscle, surface EMG (sEMG) recording, was carried out using a protocol of reflex and volitional motor tasks and was analyzed using a vector-based tool that calculates index values that relate a distribution of multi-muscle activation pattern of each SCI subject to the prototype obtained from non-injured subject group and presents overall magnitude as a separate value. Functional Independence Measure motor sub-scale, Spinal Cord Injury Independence Measure (SCIM-III), and Walking Index for Spinal Cord Injury (WISCI) scale scores were compared to neurophysiological parameters. RESULTS: AIS category and injury level correlated significantly with the WISCI and SCIM mobility sub-scales. sEMG-derived parameters were significantly correlated with SCIM and WISCI scores but only for examinations carried out 48 or more days post injury. CONCLUSION: These results supported the hypothesis that clinically relevant function after SCI is related to the degree to which functional organization within the central nervous system is disrupted. Further, due likely to the constraints placed on the expression of functional ability by early post injury immobilization and hospitalization, neurophysiological assessment of motor function may provide better sensitivity and reliability than can be obtained using the clinical function scales examined here within the early period after injury. PMID- 24223569 TI - Identification of the Epileptogenic Zone from Stereo-EEG Signals: A Connectivity Graph Theory Approach. AB - In the context of focal drug-resistant epilepsies, the surgical resection of the epileptogenic zone (EZ), the cortical region responsible for the onset, early seizures organization, and propagation, may be the only therapeutic option for reducing or suppressing seizures. The rather high rate of failure in epilepsy surgery of extra-temporal epilepsies highlights that the precise identification of the EZ, mandatory objective to achieve seizure freedom, is still an unsolved problem that requires more sophisticated methods of investigation. Despite the wide range of non-invasive investigations, intracranial stereo-EEG (SEEG) recordings still represent, in many patients, the gold standard for the EZ identification. In this contest, the EZ localization is still based on visual analysis of SEEG, inevitably affected by the drawback of subjectivity and strongly time-consuming. Over the last years, considerable efforts have been made to develop advanced signal analysis techniques able to improve the identification of the EZ. Particular attention has been paid to those methods aimed at quantifying and characterizing the interactions and causal relationships between neuronal populations, since is nowadays well assumed that epileptic phenomena are associated with abnormal changes in brain synchronization mechanisms, and initial evidence has shown the suitability of this approach for the EZ localization. The aim of this review is to provide an overview of the different EEG signal processing methods applied to study connectivity between distinct brain cortical regions, namely in focal epilepsies. In addition, with the aim of localizing the EZ, the approach based on graph theory will be described, since the study of the topological properties of the networks has strongly improved the study of brain connectivity mechanisms. PMID- 24223570 TI - Muscarinic modulation of high frequency oscillations in pedunculopontine neurons. AB - We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9-12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around -20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 +/- 1 Hz (with CAR) vs. 23 +/- 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5'-[beta-thio] diphosphate trilithium salt (GDP-beta-S), and the G-protein agonist 5'-[gamma-thio] triphosphate trilithium salt (GTP-gamma-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q type calcium channel-mediated gamma oscillations to occur. PMID- 24223571 TI - Resting state interhemispheric motor connectivity and white matter integrity correlate with motor impairment in chronic stroke. AB - Functional and structural reorganization in the brain occurs after stroke. The ability to predict motor outcomes may depend on patterns of brain functional and structural connectivity. We tested the hypothesis that alterations in motor transcallosal and corticospinal connections correlate with motor impairment in patients with chronic stroke. Eleven ischemic stroke patients underwent the Upper Extremity Fugl-Meyer (UE-FM) assessment, resting state functional magnetic resonance imaging, and diffusion tensor imaging (DTI). Twelve healthy control subjects underwent DTI. We assessed the temporal coupling in neural activity between interhemispheric motor cortex, and white matter integrity by means of fractional anisotropy (FA), in the transcallosal motor fibers and corticospinal tract. Partial correlation analyses were performed to determine whether these connectivity measures correlate with Upper UE-FM scores. Patients compared to controls had reduced FA in common voxels of transcallosal motor and ipsilesional corticospinal fibers. Within the patient group those with higher interhemispheric motor cortex connectivity and higher FA in the transcallosal motor fibers were less impaired. The results show that markers of functional and structural motor cortex connectivity correlate with motor impairment in the chronic stage of stroke. PMID- 24223572 TI - FMRI of working memory impairment after recovery from subarachnoid hemorrhage. AB - Recovery from aneurysmal subarachnoid hemorrhage (SAH) is often incomplete and accompanied by subtle but persistent cognitive deficits. Previous neuropsychological reports indicate these deficits include most prominently memory impairment, with working memory particularly affected. The neural basis of these memory deficits remains unknown and unexplored by functional magnetic resonance imaging (fMRI). In the present study, patients who experienced (SAH) underwent fMRI during the performance of a verbal working memory paradigm. Behavioral results indicated a subtle but statistically significant impairment relative to healthy subjects in working memory performance accuracy, which was accompanied by relatively increased blood-oxygen level dependent signal in widespread left and right hemisphere cortical areas during periods of encoding, maintenance, and retrieval. Activity increases remained after factoring out inter individual differences in age and task performance, and included most notably left hemisphere regions associated with phonological loop processing, bilateral sensorimotor regions, and right hemisphere dorsolateral prefrontal cortex. We conclude that deficits in verbal working memory following recovery from (SAH) are accompanied by widespread differences in hemodynamic correlates of neural activity. These differences are discussed with respect to the immediate and delayed focal and global brain damage that can occur following (SAH), and the possibility that this damage induces subcortical disconnection and subsequent decreased efficiency in neural processing. PMID- 24223573 TI - Do studies on cortical plasticity provide a rationale for using non-invasive brain stimulation as a treatment for Parkinson's disease patients? AB - Animal models of Parkinson's disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field. PMID- 24223574 TI - High incidence of hypoglycemia from an audit of glycemic control and management in patients with diabetes in a cardiac unit. PMID- 24223575 TI - Ammonia-oxidizer communities in an agricultural soil treated with contrasting nitrogen sources. AB - The community of ammonia-oxidizing prokaryotes was examined in an agricultural soil treated for six seasons with contrasting nitrogen (N) sources. Molecular tools based on the genes encoding ammonia monooxygenase were used to characterize the ammonia oxidizer (AO) communities and their abundance. Soil DNA was extracted from soils sampled from silage corn plots that received no additional N (control), dairy waste compost, liquid dairy waste (LW), and ammonium sulfate (AS) treatments at approximately 100 and 200 kg available N ha(-1) over 6 years. The N treatment affected the quantity of AO based on estimates of amoA by real time PCR. Ammonia oxidizing bacteria (AOB) were higher in soils from the AS200, AS100, and LW200 treatments (2.5 * 10(7), 2.5 * 10(7), and 2.1 * 10(7)copies g( 1) soil, respectively) than in the control (8.1 * 10(6) copies g(-1) soil) while the abundance of amoA encoding archaea [ammonia oxidizing archaea (AOA)] was not significantly affected by treatment (3.8 * 10(7) copies g(-1) soil, average). The ratio of AOA/AOB was higher in the control and compost treated soils, both treatments have the majority of their ammonium supplied through mineralization of organic nitrogen. Clone libraries of partial amoA sequences indicated AOB related to Nitrosospira multiformis and AOA related to uncultured Nitrososphaera similar to those described by soil fosmid 54d9 were prevalent. Profiles of the amoC-amoA intergenic region indicated that both Nitrosospira- and Nitrosomonas-type AOB were present in all soils examined. In contrast to the intergenic amoC-amoA profile results, Nitrosomonas-like clones were recovered only in the LW200 treated soil-DNA. The impact of 6 years of contrasting nitrogen sources applications caused changes in AO abundance while the community composition remained relatively stable for both AOB and AOA. PMID- 24223576 TI - Four Promoters of IRF5 Respond Distinctly to Stimuli and are Affected by Autoimmune-Risk Polymorphisms. AB - INTRODUCTION: Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis affect millions of people worldwide. Interferon regulatory factor 5 (IRF5) contains polymorphisms associated with these autoimmune diseases. Two of these functional polymorphisms are found upstream of the IRF5 gene. rs2004640, which is a single nucleotide polymorphism and the CGGGG insertion/deletion (indel) were studied. IRF5 uses four different promoters for its four first exons: 1A, 1B, 1C, and 1D. Each promoter was analyzed, including functional differences due to the autoimmune-risk polymorphisms. RESULTS: IRF5 promoters were analyzed using ChIP-Seq data (ENCODE database) and the FactorBook database to define transcription factor binding sites. To verify promoter activity, the promoters were cloned into luciferase plasmids. Each construct exhibited luciferase activity. Exons 1A and 1D contain putative PU.1 and NFkB binding sites. Imiquimod, a Toll-like receptor 7 (TLR7) ligand, was used to activate these transcription factors. IRF5 levels were doubled after imiquimod treatment (p < 0.001), with specific increases in the 1A promoter (2.2-fold, p = 0.03) and 1D promoter (2.8-fold, p = 0.03). A putative binding site for p53, which affects apoptosis, was found in the promoter for exon 1B. However, site-directed mutagenesis of the p53 site showed no effect in a reporter assay. CONCLUSION: The IRF5 exon 1B promoter has been characterized, and the responses of each IRF5 promoter to TLR7 stimulation have been determined. Changes in promoter activity and gene expression are likely due to specific and distinct transcription factors that bind to each promoter. Since high expression of IRF5 contributes to the development of autoimmune disease, understanding the source of increased IRF5 levels is key to understanding autoimmune etiology. PMID- 24223578 TI - Biofortification: how can we exploit plant science and biotechnology to reduce micronutrient deficiencies? PMID- 24223577 TI - Modulation of NK cell function by genetically coupled C-type lectin-like receptor/ligand pairs encoded in the human natural killer gene complex. AB - Functional responses of natural killer (NK) cells including eradication of "harmful" cells and modulation of immune responses are regulated by a broad variety of activating and inhibitory NK receptors. Whereas the leukocyte receptor complex (LRC) encodes for NK receptors of the immunoglobulin superfamily, genes of C-type lectin-like NK receptors are clustered in the mammalian natural killer gene complex (NKC). Besides the thoroughly studied C-type lectin-like receptors NKG2D, CD94/NKG2x, and members of the murine Ly49 subfamily, the NKC also encodes for NK receptors of the less characterized NKRP1 subfamily. The prototypic mouse NKRP1 receptor is Nkrp1c (also known as NK1.1), while human members of the NKRP1 subfamily are NKRP1A, NKp80, and NKp65. The latter are not straight homologs of mouse NKRP1 receptors, but share distinct subfamily-specific traits classifying them as members of the NKRP1 subfamily. Ligands of the human NKPR1 receptors are likewise C-type lectin-like glycoproteins belonging to the CLEC2 subfamily (i.e., LLT1, AICL, and KACL), and are encoded in the NKC in tight genetic linkage to their respective receptors. Similarly, certain members of the mouse NKRP1 subfamily interact with genetically coupled CLEC2 glycoproteins, while the reasons for this intriguing tight genetic linkage remain unknown. Recent studies provided new and unique insights into the expression, interaction, and signaling of NKRP1 receptors and their ligands, thereby substantially advancing our understanding of their function and biology. Here, we review our current knowledge on NKRP1 receptors and their genetically linked CLEC2 ligands with an emphasis on the human receptor/ligand pairs NKRP1A-LLT1, NKp80-AICL, and NKp65 KACL. PMID- 24223579 TI - Monotonicity is a key feature of genotype-phenotype maps. AB - It was recently shown that monotone gene action, i.e., order-preservation between allele content and corresponding genotypic values in the mapping from genotypes to phenotypes, is a prerequisite for achieving a predictable parent-offspring relationship across the whole allele frequency spectrum. Here we test the consequential prediction that the design principles underlying gene regulatory networks are likely to generate highly monotone genotype-phenotype maps. To this end we present two measures of the monotonicity of a genotype-phenotype map, one based on allele substitution effects, and the other based on isotonic regression. We apply these measures to genotype-phenotype maps emerging from simulations of 1881 different 3-gene regulatory networks. We confirm that in general, genotype phenotype maps are indeed highly monotonic across network types. However, regulatory motifs involving incoherent feedforward or positive feedback, as well as pleiotropy in the mapping between genotypes and gene regulatory parameters, are clearly predisposed for generating non-monotonicity. We present analytical results confirming these deep connections between molecular regulatory architecture and monotonicity properties of the genotype-phenotype map. These connections seem to be beyond reach by the classical distinction between additive and non-additive gene action. PMID- 24223580 TI - Folate-related gene variants in Irish families affected by neural tube defects. AB - Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative ("risk genotypes") and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms. PMID- 24223581 TI - The impact of commercialization on the evaluation of DNA evidence. PMID- 24223582 TI - A genome-wide association study for somatic cell score using the Illumina high density bovine beadchip identifies several novel QTL potentially related to mastitis susceptibility. AB - Mastitis is an inflammation-driven disease of the bovine mammary gland that occurs in response to physical damage or infection and is one of the most costly production-related diseases in the dairy industry worldwide. We performed a genome-wide association study (GWAS) to identify genetic loci associated with somatic cell score (SCS), an indicator trait of mammary gland inflammation. A total of 702 Holstein-Friesian bulls were genotyped for 777,962 single nucleotide polymorphisms (SNPs) and associated with SCS phenotypes. The SCS phenotypes were expressed as daughter yield deviations (DYD) based on a large number of progeny performance records. A total of 138 SNPs on 15 different chromosomes reached genome-wide significance (corrected p-value <= 0.05) for association with SCS (after correction for multiple testing). We defined 28 distinct QTL regions and a number of candidate genes located in these QTL regions were identified. The most significant association (p-value = 1.70 * 10(-7)) was observed on chromosome 6. This QTL had no known genes annotated within it, however, the Ensembl Genome Browser predicted the presence of a small non-coding RNA (a Y RNA gene) in this genomic region. This Y RNA gene was 99% identical to human RNY4. Y RNAs are a rare type of non-coding RNA that were originally discovered due to their association with the autoimmune disease, systemic lupus erythematosus. Examining small-RNA sequencing (RNAseq) data being generated by us in multiple different mastitis-pathogen challenged cell-types has revealed that this Y RNA is expressed (but not differentially expressed) in these cells. Other QTL regions identified in this study also encoded strong candidate genes for mastitis susceptibility. A QTL region on chromosome 13, for example, was found to contain a cluster of beta defensin genes, a gene family with known roles in innate immunity. Due to the increased SNP density, this study also refined the boundaries for several known QTL for SCS and mastitis. PMID- 24223583 TI - ROS-mediated regulation of CXCR4 in cancer. AB - Oxidative stress and the accumulation of reactive oxygen species (ROS) play a role in cancer cells developing an advanced, phenotypic signature that associates with metastasis and progression. Increased ROS concentrations are involved in promoting cancer development and metastasis by inducing expression of oncogenes, suppressing activity of anti-survival molecules and by activating various cell survival and proliferation signaling pathways. Oxidative stress is higher in the epithelium of cancer patients than patients without the disease, and antioxidant trials are currently being explored as a therapeutic option. However, studies have shown that ROS increases expression of CXCR4 in cancer and immune cells. CXCR4 expression in tumors strongly correlates to metastasis and poor prognosis. Herein, we discuss an emerging relationship between ROS and CXCR4 in cancer cells. PMID- 24223584 TI - Neuroprotective Properties of a Novel Non-Thiazoledinedione Partial PPAR- gamma Agonist against MPTP. AB - Activation of the peroxisome proliferator activated receptor-gamma (PPAR)- gamma is proposed as a neuroprotective strategy to treat neurodegenerative disorders. In this study, we examined if LSN862 (LSN), a novel non-thiazoledinedione partial PPAR- gamma agonist, was neuroprotective in a mouse model of Parkinson's disease (PD) and assessed possible mechanisms of action. LSN (3, 10, or 30 mg/kg) or vehicle was orally administered daily to C57BL/6 and antioxidant response element human placental alkaline phosphatase (ARE-hPAP) reporter mice 3 days prior to 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, i.p. * 5 days) or PBS administration. LSN elicited a dose-dependent preservation of dopaminergic nigrostriatal innervation that was not associated with inhibition of MPTP metabolism or activation of Nrf2-ARE, although changes in NQO1 and SOD2 mRNA were observed. A significant dose-dependent downregulation in MAC-1 and GFAP positive cells was observed in MPTP + LSN-treated mice as well as significant downregulation of mRNA expression levels of these inflammatory markers. MPTP induced increases in PPAR- gamma and PGC1 alpha expression were ameliorated by LSN dosing. Our results demonstrate that oral administration of LSN is neuroprotective against MPTP-induced neurodegeneration, and this effect is associated with downregulation of neuroinflammation, decreased oxidative stress, and modulation of PPAR- gamma and PGC1 alpha expression. These results suggest that LSN can be a candidate alternative non-thiazoledinedione partial PPAR- gamma agonist for neuroprotective treatment of PD. PMID- 24223586 TI - Effect of capacitive radiofrequency on the fibrosis of patients with cellulite. AB - Background. Cellulite is a type of lipodystrophy that develops primarily from an alteration in blood circulation or of the lymphatic system that causes structural changes in subcutaneous adipose tissue, collagen, and adjacent proteoglycans. The radiofrequency devices used for cutaneous applications have shown different physiological treatment effects, but there is controversy about the suitable parameters for this type of treatment. Objectives. The aim of this study was to evaluate the effects of low-temperature radiofrequency to confirm the thinning of the collagen tissue and interlobular septa and consequent improvement of cellulite. Methods. A sample of eight women was used to collect ultrasonographic data with a 12 MHz probe that measured collagen fiber thickness. The Vip Electromedicina (Argentina) device, frequency of 0.55 MHz and active electrode 3.5 cm in diameter (area = 9.61 cm(2)), was applied to a 10 cm(2) region of the gluteal region for 2 minutes per area of active electrode, during 10 biweekly sessions. Results. The Wilcoxon matched paired test was applied using GraphPad InStat 3.01 for Win95-NT software. Pre- and posttreatment mean collagen fiber thickness showed a 24.66% reduction from 1.01 to 0.67 mm. Statistical analysis using the Wilcoxon matched paired test obtained a significant two-tailed P value of 0.0391. Conclusion. It was concluded that the use of more comfortable temperatures favored a reduction in fibrous septum thickness and consequent cellulite improvement, evidenced by the lower degree of severity and decrease in interlobular septal thickness. PMID- 24223585 TI - Chronic urticaria: Indian context-challenges and treatment options. AB - Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal) is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management. PMID- 24223587 TI - Comparing Imputation Procedures for Affymetrix Gene Expression Datasets Using MAQC Datasets. AB - Introduction. The microarray datasets from the MicroArray Quality Control (MAQC) project have enabled the assessment of the precision, comparability of microarrays, and other various microarray analysis methods. However, to date no studies that we are aware of have reported the performance of missing value imputation schemes on the MAQC datasets. In this study, we use the MAQC Affymetrix datasets to evaluate several imputation procedures in Affymetrix microarrays. Results. We evaluated several cutting edge imputation procedures and compared them using different error measures. We randomly deleted 5% and 10% of the data and imputed the missing values using imputation tests. We performed 1000 simulations and averaged the results. The results for both 5% and 10% deletion are similar. Among the imputation methods, we observe the local least squares method with k = 4 is most accurate under the error measures considered. The k nearest neighbor method with k = 1 has the highest error rate among imputation methods and error measures. Conclusions. We conclude for imputing missing values in Affymetrix microarray datasets, using the MAS 5.0 preprocessing scheme, the local least squares method with k = 4 has the best overall performance and k nearest neighbor method with k = 1 has the worst overall performance. These results hold true for both 5% and 10% missing values. PMID- 24223588 TI - Nonalcoholic Fatty liver disease: its mechanisms and complications. PMID- 24223589 TI - Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer. AB - High-level evidence supports adjuvant radiotherapy for rectal cancer. We examined the influence of sociodemographic factors on patterns of adjuvant radiotherapy for resected Stage II/III rectal cancer. Methods. Patients undergoing surgical resection for stage II/III rectal cancer were identified in SEER registry. Results. A total of 21,683 patients were identified. Majority of patients were male (58.8%), white (83%), and with stage III (54.9%) and received radiotherapy (66%). On univariate analysis, male gender, stage III, younger age, year of diagnosis, and higher socioeconomic status (SES) were associated with radiotherapy. Radiotherapy was delivered in 84.4% of patients <50; however, only 32.8% of those are >80 years. Logistic regression demonstrated a significant increase in the use of radiotherapy in younger patients who are <50 (OR, 10.3), with stage III (OR, 1.21), males (OR, 1.18), and with higher SES. Conclusions. There is a failure to conform to standard adjuvant radiotherapy in one-third of patients, and this is associated with older age, stage II, area-level of socioeconomic deprivation, and female sex. PMID- 24223590 TI - Verrucous papillary lesions: dilemmas in diagnosis and terminology. AB - Verrucous papillary lesions (VPLs) of oral cavity are diagnostically challenging as they include a spectrum of benign, potentially malignant, and frankly malignant lesions. A majority of the benign VPLs have viral aetiology and include commonly occurring squamous papilloma along with verruca vulgaris, focal epithelial hyperplasia, and condyloma. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. Clinically and histologically oral verrucous hyperplasia, a potentially malignant disorder, resembles oral verrucous carcinoma and may be indistinguishable from one another. The most reliable way to separate these entities on routine haematoxylin-eosin stained tissue sections is to recognize the exophytic growth patterns of oral verrucous hyperplasia from the combined exophytic and endophytic growth patterns associated with verrucous carcinoma. A review of the literature showed that there is a lot of confusion regarding the current clinical and histopathological guidelines to diagnose this potentially malignant entity. The criteria elaborated by different authors in establishing the diagnosis of oral verrucous hyperplasia are discussed in detail. A brief overview of the treatment modalities adopted is also discussed. The need for establishing a clear understanding of this potentially malignant entity is stressed as it may have far reaching implications on its management. PMID- 24223591 TI - Microbial changes in subgingival plaque and polymicrobial intracellular flora in buccal cells after fixed orthodontic appliance therapy: a preliminary study. AB - The oral ecosystem is strictly related to a balance maintained by specific niches recognized as sites, where oral bacteria can metabolize avoiding the immune system response. The oral bacteria species that colonize the ecological niches vary during fixed orthodontic treatment, with a prevalence of periodontal bacterial species. Qualitative analysis of five periodontal pathogens was used to investigate the microbial colonization rate in the crevice and buccal epithelial cells. The presence of inadequate oral hygiene was considered as a modulation variable for microbial colonization. Statistical analysis was performed by Fisher's exact test, ANOVA, and Pearson correlation. A P value lower than 0.05 was assumed as statistically significant. Tannerella forsythia was the only periodontal pathogen detected with a statistically admissible frequency. The positivity for Tannerella forsythia was correlated to sampling time and oral hygiene motivation. In buccal epithelial cells, both factors contributed to microbial decrease (P < 0.05), whereas, in crevice, oral hygiene motivation promoted a decrease in the microbial colonization rate (P < 0.05). According to microbiological findings, it is possible to identify how correct motivation for oral hygiene is more than enough to modulate or to avoid an upset of the oral ecosystem balance in early stages of orthodontic treatment. PMID- 24223592 TI - Characteristics of 2 Different Commercially Available Implants with or without Nanotopography. AB - The aim of this study was to assess histologically and histomorphometrically the early bone forming properties after 3 weeks for 2 commercially available implants, one supposedly possessing nanotopography and one without, in a rabbit femur model. Twenty-four implants divided equally into 2 groups were utilized in this study. The first group (P-I MICRO+NANO) was a titanium oxide (TiO2) microblasted and noble gas ion bombarded surface while the second group (Ospol) was anodic oxidized surface with calcium and phosphate incorporation. The implants were placed in the rabbit femur unicortically and were allowed to heal for 3 weeks. After euthanasia, the samples were subjected to histologic sectioning and bone-implant contact and bone area were evaluated histomorphometrically under an optical microscope. The histomorphometric evaluation presented that the P-I MICRO+NANO implants demonstrated significantly higher new bone formation as compared to the Ospol implants. Within the limitations of this study, the results suggested that nanostructures presented significantly higher bone formation after 3 weeks in vivo, and the effect of chemistry was limited, which is indicative that nanotopography is effective at early healing periods. PMID- 24223593 TI - The innate immune system in Alzheimer's disease. AB - Alzheimer's disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid beta (A beta ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD. PMID- 24223594 TI - Quantifying Changes in the Cellular Thiol-Disulfide Status during Differentiation of B Cells into Antibody-Secreting Plasma Cells. AB - Plasma cells produce and secrete massive amounts of disulfide-containing antibodies. To accommodate this load on the secretory machinery, the differentiation of resting B cells into antibody-secreting plasma cells is accompanied by a preferential expansion of the secretory compartments of the cells and by an up-regulation of enzymes involved in redox regulation and protein folding. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated proteins in whole cells. The results show that while the global thiol-disulfide state is affected to some extent by the differentiation, steady-state levels of glutathionylated protein thiols are less than 0.3% of the total protein cysteines, even in fully differentiated cells, and the overall protein redox state is not affected until late in differentiation, when large-scale IgM production is ongoing. A general expansion of the ER does not affect global protein redox status until an extensive production of cargo proteins has started. PMID- 24223595 TI - Antimicrobial and Herbal Drug Resistance in Enteric Bacteria Isolated from Faecal Droppings of Common House Lizard/Gecko (Hemidactylus frenatus). AB - From 194 faecal dropping samples of common house geckos collected from offices (60), houses (88), integrated farm units (IFS,18) and hostels, guest houses, and dining rooms of different canteen/mess (HGM, 28), 326 bacterial isolates of enteric bacteria belonging to 17 genera and 34 species were detected. Escherichia coli were the most frequently (39) isolated followed by Citrobacter freundii (33), Klebsiella pneumonia (27), Salmonella indica (12), Enterobacter gergoviae (12), and Ent. agglomerans (11). Other important bacteria isolated from gecko droppings were Listonella damsela (2), Raoultella terrigena (3), S. salamae (2), S. houtenae (3), Edwardsiella tarda (4), Edwardsiella hoshinae (1), and Klebsiella oxytoca (2). Of the 223 isolates tested for antimicrobial drug sensitivity, 27 (12.1%) had multiple drug resistance (MDR). None of the salmonellae or edwardsiellae had MDR however, MDR strains were significantly more common among Escherichia spp. (P = 1.9 * 10(-5)) and isolates from IFS units (P = 3.58 * 10(-23)). The most effective herbal drug, Ageratum conyzoides extract, inhibited growth of only 27.8% of strains tested followed by ethanolic extract of Zanthoxylum rhetsa (13.9%), eucalyptus oil (5.4%), patchouli oil (5.4%), lemongrass oil (3.6%), and sandalwood oil (3.1%), and Artemisia vulgaris essential oil (3.1%). PMID- 24223596 TI - The role of Klebsiella in Crohn's disease with a potential for the use of antimicrobial measures. AB - There is a general consensus that Crohn's disease (CD) develops as the result of immune-mediated tissue damage triggered by infections with intestinal microbial agents. Based on the results of existing microbiological, molecular, and immunological studies, Klebsiella microbe seems to have a key role in the initiation and perpetuation of the pathological damage involving the gut and joint tissues in patients with CD. Six different gastroenterology centres in the UK have reported elevated levels of antibodies to Klebsiella in CD patients. There is a relationship between high intake of starch-containing diet, enhanced growth of gut microbes, and the production of pullulanases by Klebsiella. It is proposed that eradication of these microbes by the use of antibiotics and low starch diet, in addition to the currently used treatment, could help in alleviating or halting the disease process in CD. PMID- 24223597 TI - Clinical efficacy and mechanism of probiotics in allergic diseases. AB - A complex interplay between genetic and environmental factors partially contributes to the development of allergic diseases by affecting development during prenatal and early life. To explain the dramatic increase in the prevalence of allergic diseases, the hygiene hypothesis proposed that early exposure to infection prevented allergic diseases. The hygiene hypothesis has changed to the microbial hypothesis, in which exposure to microbes is closely linked to the development of the early immune system and allergic diseases. The intestinal flora may contribute to allergic disease through its substantial effect on mucosal immunity. Based on findings that exposure to microbial flora early in life can change the Th1/Th2 balance, thus favoring a Th1 cell response, probiotics may be beneficial in preventing allergic diseases. However, evidence from clinical and basic research to prove the efficacy of probiotics in preventing allergy is lacking. To date, studies have yielded inconsistent findings on the usefulness of probiotics in allergic diseases. It is difficult to demonstrate an exact effect of probiotics on asthma, allergic rhinitis, and food allergy because of study limitations, such as different first supplementation period, duration, different strains, short follow-up period, and host factors. However, many studies have demonstrated a significant clinical improvement in atopic dermatitis with the use of probiotics. An accurate understanding of the development of human immunity, intestinal barrier function, intestinal microbiota, and systemic immunity is required to comprehend the effects of probiotics on allergic diseases. PMID- 24223598 TI - Kawasaki disease in infants. AB - Kawasaki disease (KD) is an acute febrile illness that is the predominant cause of pediatric acquired heart disease in infants and young children. Because the diagnosis of KD depends on clinical manifestations, incomplete cases are difficult to diagnose, especially in infants younger than 1 year. Incomplete clinical manifestations in infants are related with the development of KD associated coronary artery abnormalities. Because the diagnosis of infantile KD is difficult and complications are numerous, early suspicion and evaluation are necessary. PMID- 24223599 TI - Acute viral gastroenteritis in children hospitalized in Iksan, Korea during December 2010-June 2011. AB - PURPOSE: Viral etiology is common in cases of children with acute diarrhea, and antibiotic therapy is usually not required. Therefore, it is important to determine the distribution of common viruses among children hospitalized with acute diarrhea. METHODS: We included 186 children who suffered from acute diarrhea and were hospitalized at the Wonkwang University Hospital Pediatric ward from December 1, 2010 to June 30, 2011 in this study. Stool samples were collected and multiplex reverse transcriptase polymerase chain reaction (multiplex RT-PCR) was used to simultaneously determine the viral etiology such as rotavirus, norovirus, astrovirus, or adenovirus. RESULTS: Causative viruses were detected in 72 of the 186 cases (38.7%). The mean age of the virus-positive cases was 1 year and 9 months (range, 1 month to 11 years). Rotavirus was detected in 50/186 (26.9%); norovirus, in 18/186 (9.7%); and astrovirus, in 3/186 cases (1.6%). Adenovirus was not detected in any of the cases. Proportions of norovirus genogroups I and II were 21.1% and 78.9%, respectively. Four of the 51 rotavirus-positive cases (7.8%) had received rotavirus vaccination at least once. The mean duration of diarrhea was 2.8 days (range, 1 to 10 days) and vomiting occurred in 39 of the 72 cases (54.2%). CONCLUSION: Viral etiology was confirmed in about one-third of the children with acute diarrhea, and the most common viral agent was rotavirus, followed by norovirus. PMID- 24223600 TI - Changes of clinical characteristics and outcomes in patients with Kawasaki disease over the past 7 years in a single center study. AB - PURPOSE: This single-center study was conducted to assess the changes in epidemiological and clinical characteristics and outcomes of patients with Kawasaki disease (KD) over the past 7 years. METHODS: This retrospective study included 135 children with KD, admitted to Chungnam National University Hospital, Daejeon, between 2004 and 2005 (group A, n=53) and between 2011 and 2012 (group B, n=82). Medical records were reviewed to obtain information regarding the presenting signs and symptoms, demographic characteristics, and laboratory and echocardiographic findings associated with KD. RESULTS: The hospital admission date after onset was significantly earlier in group B than in group A (P=0.008). The proportion of patients with incomplete KD was 45.3% and 65.9% in group A and B, respectively (P=0.018). The number of pretreatment coronary artery lesions (CALs) were significantly lesser in group B than in group A. (10/53 vs. 5/82, P=0.021). No significant differences was observed in the incidence of CALs at discharge, febrile phase duration, hospital stay duration, incidence of retreatment, and intravenous immunoglobulin dose between 2 groups. The total febrile phase was shorter in patients with incomplete KD than in those with complete KD in both groups. CONCLUSION: The proportion of incomplete KD has become higher. Furthermore, early admission and management of patients with KD may be related to increased incomplete KD and decreased CALs. Therefore, we believe that a diagnostic strategy for incomplete KD should be established regardless of the presence of coronary lesions. PMID- 24223601 TI - Transcatheter closure of small ductus arteriosus with amplatzer vascular plug. AB - PURPOSE: The purpose of this study was to share our experience of transcatheter closure of small patent ductus arteriosus (PDA) by using an Amplatzer vascular plug (AVP). METHODS: We reviewed the medical records of 20 patients who underwent transcatheter closure at Samsung Medical Center and Sejong General Hospital from January 2008 to August 2012. The size and shape of the PDAs were evaluated by performing angiograms, and the PDA size and the AVP devices size were compared. RESULTS: The mean age of the patients was 54.9+/-45.7 months old. The PDAs were of type C (n=5), type D (n=12), and type E (n=3). The mean pulmonary end diameter of the PDA was 1.7+/-0.6 mm, and the aortic end diameter was 3.6+/-1.4 mm. The mean length was 7.3+/-1.8 mm. We used 3 types of AVP devices: AVP I (n=5), AVP II (n=7), and AVP IV (n=8). The ratio of AVP size to the pulmonary end diameter was 3.37+/-1.64, and AVP size/aortic end ratio was 1.72+/-0.97. The aortic end diameter was significantly larger in those cases repaired with AVP II than in the others (P=0.002). The AVP size did not significantly correlate with the PDA size, but did correlate with smaller ratio of AVP size to aortic end diameter (1.10+/ 0.31, P=0.032). CONCLUSION: Transcatheter closure of small PDA with AVP devices yielded satisfactory outcome. AVP II was equally effective with smaller size of device, compared to others. PMID- 24223602 TI - High-dose chemotherapy and autologous peripheral blood stem cell transplantation in the treatment of children and adolescents with Ewing sarcoma family of tumors. AB - PURPOSE: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. METHODS: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. RESULTS: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%+/-16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%+/-18.7% of cases with CR vs. 0% of cases with non-CR, P=0.07). CONCLUSION: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment. PMID- 24223603 TI - Klebsiella pneumoniae liver abscess in an immunocompetent child. AB - Klebsiella pneumoniae has emerged as a leading pathogen that causes pyogenic liver abscesses (PLAs) in Korea. K. pneumoniae liver abscess (KLA) is potentially life threatening, and the diagnosis is difficult. In developed countries, PLA is rarely observed in children and is frequently associated with disorders of granulocyte function and previous abdominal infection. We observed a case of KLA in a healthy 12-year-old boy. To our knowledge, this is the first reported case of KLA in an immunocompetent child without an underlying disease in Korea. The patient was treated with percutaneous catheter drainage and antibiotics. The catheter was placed in the intrahepatic abscess for 3 weeks and parenteral antibiotics (ceftriaxone and amikacin) were administered for 4 weeks, followed by oral antibiotics (cefixime) for 2 weeks. We reported this case to raise awareness of KLA in immunocompetent children among physicians, and to review the diagnosis, risk factors, potential complications, and appropriate treatment of KLA. PMID- 24223604 TI - Mycoplasma pneumoniae associated stroke in a 3-year-old girl. AB - Infectious diseases precede a significant proportion of acute ischemic strokes in children. Here, we report a case of acute ischemic stroke in a 3-year-old girl with a Mycoplasma pneumonia-associated respiratory tract infection. She developed an acquired prothrombotic state of protein S deficiency and had increased fibrinogen and fibrinogen degradation product levels and increased titer of antinuclear antibodies. However, these conditions were completely alleviated at the 1-month follow-up examination. Infection with M. pneumoniae may cause a transient prothrombotic state that can potentially cause a thrombus. PMID- 24223605 TI - Research of the methylation status of miR-124a gene promoter among rheumatoid arthritis patients. AB - OBJECTIVE: To analyze the methylation status of miR-124a loci in synovial tissues of rheumatoid arthritis (RA) patients using methylation-specific polymerase chain reaction (MSP). MATERIALS AND METHODS: DNA obtained from the frozen tissue of 7 RA samples, 6 osteoarthritis (OA) samples, and 3 healthy controls were undergoing bisulfite conversion and then analyzed for miR-124a promoter methylation using MSP assay. RESULTS: miR-124-a1 and miR-124-a2 promoter methylation were both seen in 71.4% of RA samples compared to 16.7% of OA samples. miR-124-a3 promoter methylation was seen in 57.1% of RA samples and 0% of OA samples. All the three loci were unmethylated in 3 healthy controls. CONCLUSION: The methylation status of miR-124a seen in this study concurs with that reported in tumor cells, indicating epigenetic dysregulation constituents, a mechanism in the development of rheumatoid arthritis. PMID- 24223606 TI - T helper 17 cells in autoimmune liver diseases. AB - Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4(+) T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor- beta and IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease. PMID- 24223607 TI - Microglial responses after ischemic stroke and intracerebral hemorrhage. AB - Stroke is a leading cause of death worldwide. Ischemic stroke is caused by blockage of blood vessels in the brain leading to tissue death, while intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures, exposing the brain to blood components. Both are associated with glial toxicity and neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), continually sample the environment for signs of injury and infection. Under homeostatic conditions, they have a ramified morphology and phagocytose debris. After stroke, microglia become activated, obtain an amoeboid morphology, and release inflammatory cytokines (the M1 phenotype). However, microglia can also be alternatively activated, performing crucial roles in limiting inflammation and phagocytosing tissue debris (the M2 phenotype). In rodent models, microglial activation occurs very early after stroke and ICH; however, their specific roles in injury and repair remain unclear. This review summarizes the literature on microglial responses after ischemic stroke and ICH, highlighting the mediators of microglial activation and potential therapeutic targets for each condition. PMID- 24223608 TI - The -174G/C and -572G/C interleukin 6 promoter gene polymorphisms in mexican patients with rheumatoid arthritis: a case-control study. AB - OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and 572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease. PMID- 24223609 TI - Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women's Health. AB - Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women's health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism. PMID- 24223610 TI - A Drug-Target Network-Based Approach to Evaluate the Efficacy of Medicinal Plants for Type II Diabetes Mellitus. AB - The use of plants as natural medicines in the treatment of type II diabetes mellitus (T2DM) has long been of special interest. In this work, we developed a docking score-weighted prediction model based on drug-target network to evaluate the efficacy of medicinal plants for T2DM. High throughput virtual screening from chemical library of natural products was adopted to calculate the binding affinity between natural products contained in medicinal plants and 33 T2DM related proteins. The drug-target network was constructed according to the strength of the binding affinity if the molecular docking score satisfied the threshold. By linking the medicinal plant with T2DM through drug-target network, the model can predict the efficacy of natural products and medicinal plant for T2DM. Eighteen thousand nine hundred ninety-nine natural products and 1669 medicinal plants were predicted to be potentially bioactive. PMID- 24223611 TI - Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway. AB - The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines (SP6.5 and C918) and related signaling pathways were studied and compared to effects on normal ocular cells (uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts). MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner (10, 30, and 100 MU M), with IC50 at 40.8 and 28.7 MU M in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested (300 MU M), suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and increased the expression of proapoptotic proteins (Bak and Bax) in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic (mitochondrial) pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells. PMID- 24223612 TI - Dodonaea viscosa var. angustifolia Inhibits Germ Tube and Biofilm Formation by C. albicans. AB - The virulence factors of Candida albicans are germ tube and biofilm formation, adherence to host tissues, and production of hydrolytic enzymes. This study investigated the effect of Dodonaea viscosa var. angustifolia extract on the germ tube and biofilm formation of C. albicans. Serum containing the three subinhibitory concentrations of leaf extract was inoculated with C. albicans, incubated, and viewed under a light microscope. Number of cells with germ tube was recorded and the results were analysed using Scheffe test for pairwise comparison. Biofilms were grown on coverslips in the presence of plant extracts and processed for scanning electron microscopy (SEM). Planktonic cells were grown in the presence of plant extract for 6 h and processed for electron microscopy (TEM). The crude plant extract significantly (P < 0.01) reduced the germ tube formation of C. albicans at 3.125 (85.36%), 1.56 (61.91%), and 0.78 mg/mL (26.27%) showing a concentration dependent effect. SEM results showed concentration dependent reduction in biofilm and hyphae formation. TEM results showed that the plant extract caused damage to the cell wall and cell membrane. DVA extract has ability to reduce virulence of C. albicans by inhibiting germ tube and biofilm formation through damage to the cell wall. Therefore, it has therapeutic potential. PMID- 24223614 TI - Translational research in complementary and alternative medicine. PMID- 24223615 TI - Zerumbone, a Natural Cyclic Sesquiterpene of Zingiber zerumbet Smith, Attenuates Nonalcoholic Fatty Liver Disease in Hamsters Fed on High-Fat Diet. AB - We investigated the effects of zerumbone, a natural cyclic sesquiterpene, on hepatic lipid metabolism in Syrian golden hamsters fed on high-fat diet (HFD). After being fed HFD for 2 weeks, hamsters were dosed orally with zerumbone (75, 150, and 300 mg kg(-1)) once daily for 8 weeks. After treatment with zerumbone, the plasma levels of total cholesterol (TC) and triglycerides (TGs) and the contents of TC and TG in hepatic tissue as well as homeostasis model assessment of insulin resistance were lowered, especially in the zerumbone-treated group (300 mg kg(-1)). Moreover, the histological evaluation of liver specimens demonstrated that the steatosis and inflammation in liver of zerumbone-treated groups were improved. Zerumbone exhibited the ability to decrease hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes, such as fatty acid synthase, acetyl-CoA carboxylase 1, and stearoyl-CoA desaturase 1. The hepatic mRNA expression of peroxisome proliferator-activated receptor alpha , together with its target genes including carnitine palmitoyl transferase-1, acyl-CoA oxidase, and acyl-CoA oxidase 1, was also upregulated by zerumbone. In conclusion, zerumbone improves insulin sensitivity, decreases lipogenesis, and increases lipid oxidation in the liver of HFD-fed hamsters, implying a potential application in the treatment of nonalcoholic fatty liver disease. PMID- 24223616 TI - Oat Protects against Diabetic Nephropathy in Rats via Attenuating Advanced Glycation End Products and Nuclear Factor Kappa B. AB - Oat, a rich source of soluble fiber, was considered to have a possible preventive effect on the progression of diabetic nephropathy. The present study aimed to assess this preventive activity in a rat model of diabetic nephropathy. Adult Wister rats were injected by streptozotocin (65 mg/kg). Animals were fed with normal diet or with a diet containing 20% oat (W/W) for 21 weeks. At the end of 21 weeks, all the kidney tissues were collected for various examinations. Our results suggested that oat could decrease the Scr and glucose level in blood of diabetic rats significantly (P < 0.05), and increase the creatinine clearance (P < 0.01). In histopathological examination, oat-fed rats showed a significant decrease in glomerulus segmented sclerosis and incidence of tubule vacuolar degeneration. By ELISA, we reported that oat feeding resulted in decreasing the levels of IL-6 and AGE in serum and kidney homogenate. In addition, the levels of oxidative stress markers were markedly improved as a result of oat feeding. Furthermore, using EMSA, we showed that oat attenuated the activation of NF kappaB. Using RT-PCR, we found that oat could downregulate the TGF-beta1 and RAGE expression at mRNA levels. This study suggests that oat can suppress diabetic nephropathy in rats effectively and may slow down the renal fibrosis by the disruption of the detrimental AGE-RAGE-NFkappaB axis. PMID- 24223617 TI - Antiosteoporosis effect of radix scutellariae extract on density and microstructure of long bones in tail-suspended sprague-dawley rats. AB - Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect of Radix Scutellariae extract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse induced osteoporosis. PMID- 24223618 TI - BNC Protects H9c2 Cardiomyoblasts from H 2 O 2 -Induced Oxidative Injury through ERK1/2 Signaling Pathway. AB - Buchang naoxintong capsule (BNC) is a traditional Chinese medicine approved for the treatment of cerebrovascular and cardiovascular diseases. However, little is known about the specific protective function or mechanism by which BNC protects against myocardial injury. This research was designed to investigate the cardioprotective effects of BNC in vitro model of hydrogen peroxide (H2O2) induced H9c2 rat cardiomyoblasts. BNC intestinal absorption liquid was used in this study instead of drug-containing serum or extracting solution. Our study revealed that BNC preconditioning enhanced antioxidant function by increasing the activities of total-antioxygen capacity, total-superoxide dismutase, and catalase and by decreasing the production of reactive oxygen species and malondialdehyde. BNC preconditioning also activated extracellular signal-regulated kinases (ERK1/2) and inhibited apoptosis-related proteins such as poly ADP-ribose polymerase (PARP) and caspase-3. Additionally, preincubation with BNC reduced intracellular Ca(2+) concentration, improved mitochondrial membrane potential, and decreased the apoptosis rate of H9c2 cells in a dose-dependent manner. These data demonstrated that BNC protects H9c2 cardiomyoblasts from H2O2-induced oxidative injury by increasing antioxidant abilities, activating ERK1/2, and blocking Ca(2+)-dependent and mitochondria-mediated apoptosis. Based on our results, the potency of BNC for protecting H9c2 cells from oxidative damage is comparable to that of trimetazidine. PMID- 24223619 TI - Ego and spiritual transcendence: relevance to psychological resilience and the role of age. AB - The paper investigates different approaches of transcendence in the sense of spiritual experience as predictors for general psychological resilience. This issue is based on the theoretical assumption that resilience does play a role for physical health. Furthermore, there is a lack of empirical evidence about the extent to which spirituality does play a role for resilience. As potential predictors for resilience, ego transcendence, spiritual transcendence, and meaning in life were measured in a sample of 265 people. The main result of a multiple regression analysis is that, in the subsample with people below 29 years, only one rather secular scale that is associated with ego transcendence predicts resilience, whereas for the older subsample of 29 years and above, spiritual transcendence gains both a positive (oneness and timelessness) and a negative (spiritual insight) relevance to psychological resilience. On the one hand, these results concur with previous studies that also found age-related differences. On the other hand, it is surprising that the MOS spiritual insight predicts psychological resilience negatively, the effect is increasing with age. One possible explanation concerns wisdom research. Here, an adaptive way of dealing with the age-related loss of control is assumed to be relevant to successful aging. PMID- 24223620 TI - Theoretical Study of a Nonpeptidic Polydisulfide alpha-Helix. AB - A carbon-sulfur molecule has been designed as a mimic of peptides. Density functional theory calculations showed that the oxidation of 10 moles of methanedithiol led to a polydisulfide oligomer, HS(CH2SS)9CH2SH. The polydisulfide can adopt an alpha-helix type of secondary structure, where the chain is coiled. Unlike proteins, the S-S bonds in the polydisulfide function as secondary rather than tertiary structural elements. The helix contains 8 non hydrogen atoms per turn, 2.7 A methylenes per turn, a pitch distance of 8.6 A, and a radius of 1.00 A. The methylene sites could carry R group residues similar to amino acids. PMID- 24223621 TI - Transient dynamics of an elastic capsule in a microfluidic constriction. AB - In this paper we investigate computationally the transient dynamics of an elastic capsule flowing in a square microchannel with a rectangular constriction, and compare it with that of a droplet. The confinement and expansion dynamics of the fluid flow results in a rich deformation behavior for the capsule, from an elongated shape at the constriction entrance, to a flattened parachute shape at its exit. Larger capsules are shown to take more time to pass the constriction and cause higher additional pressure difference, owing to higher flow blocking. Our work highlights the effects of two different mechanisms for non-tank-treading transient capsule dynamics. The capsule deformation results from the combined effects of the surrounding and inner fluids' normal stresses on the soft particle's interface, and thus when the capsule viscosity increases, its transient deformation decreases, as for droplets. However, the capsule deformation is not able to create a strong enough inner circulation (owing to restrictions imposed by the material membrane), and thus the viscosity ratio does not affect much the capsule velocity and the additional pressure difference. In addition, the weak inner circulation results in a positive additional pressure difference DeltaP+ even for low-viscosity capsules, in direct contrast to low viscosity droplets which create a negative DeltaP+. Our findings suggest that the high cytoplasmatic viscosity, owing to the protein hemoglobin required for oxygen transport, does not affect adversely the motion of non-tank-trading erythrocytes in vascular capillaries. PMID- 24223622 TI - Household dynamics and socioeconomic conditions in the context of incident adolescent orphaning in KwaZulu-Natal, South Africa. AB - We compared demographics, socioeconomic status, and food insecurity between households with and without recent orphans in a region of high HIV/AIDS mortality in South Africa. We recruited a cohort of 197 recent orphans and 528 non-orphans ages 9-15 and their households using stratified cluster sampling. Households were classified into three groups: orphan-only (N=50); non-orphan-only (N=377); and mixed (N=210). Between September 2004 and May 2007, households were interviewed three times regarding demographics, income and assets, and food insecurity. Baseline bivariate associations were assessed using chi-square- and t-tests. Longitudinal bivariate associations and multivariate models were tested using generalized estimating equations. At baseline, mixed households generally exhibited greater characteristics of vulnerability than orphan and non-orphan households. They were larger, had older, less educated household heads, and reported a much smaller annual per capita income. Orphan households were more likely to report a death in the previous year, and less likely to have an adult employed. These differences persisted over the study. Even non-orphan households exhibited characteristics of vulnerability, with 14% reporting a death one year before baseline, 45% of whom were prime-age adults. At baseline, a much smaller proportion of orphan households reported receiving the child support grant than the other household types, but notably, there were no differences among households in receipt of the grant by Round 3. Household food insecurity was highly prevalent: more than one in five orphan-only and mixed households reported being food insecure in the previous month. These findings suggest that the effects of HIV/AIDS only exacerbate existing high levels of poverty in the district, as virtually all households are vulnerable regardless of orphan status. Community-level programs must help families address a spectrum of needs, including food security, caregiving, and financial support, as well as better target social welfare grants and make them more accessible to vulnerable households. PMID- 24223623 TI - Computational methodology of optical molecular imaging. PMID- 24223624 TI - Understanding Personality and Predicting Outcomes: The Utility of Cognitive Behavioral Probes of Approach and Avoidance Motivation. AB - Approach and avoidance motivation may represent important explanatory constructs in understanding how individuals differ. Such constructs have primarily been assessed in self-reported terms, but there are limitations to self-reports of motivation. Accordingly, the present review concentrates on the potential utility of implicit cognitive-behavioral probes of approach and avoidance motivation in modeling and understanding individual differences. The review summarizes multiple lines of research that have documented the utility of such probes to the personality-processing interface. Although multiple gaps to our knowledge exist, and are acknowledged, the value of such implicit cognitive-behavioral assessments is emphasized both in modeling multiple sub-components of approach and avoidance motivation and in showing that such tendencies matter in ways that transcend momentary experiences or manipulations. PMID- 24223626 TI - Characteristics of gastrointestinal symptoms and function following endoscopic submucosal dissection and treatment of the gastrointestinal symptoms using rikkunshito. AB - The aim of the present study was to investigate the gastrointestinal (GI) symptoms and gastric emptying following endoscopic submucosal dissection (ESD), as well as to evaluate a novel treatment strategy using rikkunshito, a traditional Japanese herbal medicine. GI symptoms and gastric emptying were evaluated 6-8 days after ESD as part of the Step I study. In the Step 1 study, the Gastrointestinal Symptom Rating Scale (GSRS) scores of the two groups after 4 and 8 weeks of treatment with either a proton pump inhibitor (PPI; PPI monotreatment group, n=5) or a PPI plus rikkunshito (PPI + rikkunshito group, n=8) were compared against baseline values. Abdominal pain and constipation occurred in the majority of patients after ESD. The mean T-max 6-8 days after gastric emptying was 75.4+/-13.6 min, which was significantly longer compared with that reported in healthy subjects (43.9+/-10.3 min). In the Step 2 study, the total GSRS score was significantly improved only in the PPI + rikkunshito group after 8 weeks of treatment. In conclusion, ESD affects gastric emptying and is associated with an increased incidence of upper GI symptoms such as abdominal pain and indigestion. Rikkunshito may be useful as a novel supporting therapeutic drug for the treatment of GI symptoms in patients who have undergone ESD. PMID- 24223625 TI - CHROMATOGRAPHIC ANALYSIS OF DRUG INTERACTIONS IN THE SERUM PROTEOME. AB - The binding of drugs with serum proteins and binding agents such as human serum albumin, alpha1-acid glycoprotein, and lipoproteins is an important process in determining the activity and fate of many pharmaceuticals in the body. A variety of techniques have been used to study drug interactions with serum proteins, but there is still a need for faster or better methods for such work. High performance liquid chromatography (HPLC) is one tool that has been utilized in many formats for these types of measurements. Advantages of using HPLC for this application include its speed and precision, its ability to be automated, its good limits of detection, and its compatibility with a wide range of assay formats and detectors. This review will discuss various approaches in which HPLC can be employed for the study of drug-protein interactions. These techniques include the use of soluble proteins in zonal elution and frontal analysis methods or vacancy techniques such as the Hummel-Dreyer method. Zonal elution and frontal analysis methods that make use of immobilized proteins and high-performance affinity chromatography will also be presented. A variety of applications will be examined, ranging from the determination of free drug fractions to the measurement of the strength or rate of a drug-protein interaction. Newer developments that will be discussed include recent work in the creation of novel mathematical approaches for HPLC studies of drug-protein binding, the use of HPLC methods for the high-throughput screening of drug-protein binding, and the creation and use of affinity monoliths or affinity microcolumns for examining drug-protein systems. PMID- 24223627 TI - Treatment outcome in patients with stage III breast cancer treated with neoadjuvant chemotherapy. AB - Despite the good responses of patients (pts) with stage III breast cancer to neoadjuvant chemotherapy (NAC), most eventually relapse and have a poor prognosis. We investigated the prognostic indicators in pts with stage III breast cancer treated with NAC, using epirubicin and/or docetaxel. A total of 22 women with stage III breast cancer underwent NAC between January 2005 and May 2011. The regimens of NAC comprised ED (epirubicin 60 mg/m2 and docetaxel 60 mg/m2) in 10 cases, FEC (fluorouracil 500 mg/m2, epirubicin 75-100 mg/m2 and cyclophosphamide 500 mg/m2) in 10 cases and EC (epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) in two cases. Following four cycles of each regimen, a further four cycles of D (docetaxel 70 mg/m2) were undertaken in nine cases. Subsequent to the completion of NAC and surgery, we assessed the clinicopathological results and performed prognostic analyses. Statistical analyses concerning disease-free survival (DFS) or overall survival (OS) were conducted by a Cox proportional hazard model. The median survival time was 66 months and there were 12 distant metastases and two local recurrences. Multivariate analyses showed the number of metastatic axillary lymph nodes (ALNs) [hazard ratio (HR), 1.079; P=0.023] was correlated with DFS, while the Ki-67 labeling index (HR, 1.109; P=0.042) and the number of meta-static ALNs (HR, 1.087; P=0.023) were correlated with OS. In conclusion, even if pts with stage III breast cancer show good responses to NAC using epirubicin and/or docetaxel, the majority eventually relapse and have a poor prognosis. The Ki-67 labeling index and the number of involved ALNs are suggested as prognostic indicators in stage III breast cancer. PMID- 24223628 TI - Inhibition of fibrosis and inflammation by triple therapy with pirfenidone, edaravone and erythropoietin in rabbits with drug-induced lung injury: comparison of CT imaging and pathological findings. AB - In a rabbit model of bleomycin-induced lung injury, computed tomography (CT) and pathological studies were conducted to investigate whether the progression of this injury is inhibited by pirfenidone and by triple therapy with pirfenidone, edaravone and erythropoietin. We divided nine rabbits with bleomycin-induced lung injury into three equally sized groups. Group 1 served as the control, group 2 received pirfenidone alone and group 3 was treated with pirfenidone, edaravone and erythropoietin. Multidetector CT (MDCT) scans were acquired immediately after the administration of bleomycin, and further scans were performed on days 14 and 28. The area of abnormal opacity was calculated. The rabbit lungs were removed and the size of abnormal areas in macroscopic specimens was calculated and the degree of fibrosis and inflammation in microscopic specimens was scored. In order, the average size of the area of abnormal opacity on CT scans was largest in group 1, followed by groups 2 and 3. On day 28, the area of opacity was significantly smaller in group 3 than in group 1 (P=0.071). The average size of the area of abnormal opacity on macroscopic findings was largest in group 1, followed in order by groups 2 and 3; the difference between group 1 and 3 was significant (P<0.05). The average fibrosis score was highest in group 3 followed by groups 2 and 1. By contrast, the average inflammation score was highest in group 2 followed by groups 1 and 3. Although the administration of pirfenidone alone slowed the progression of bleomycin-induced lung injury, the triple-drug combination was more effective. PMID- 24223629 TI - Technique for the safe placement of a biodegradable stent into the common bile duct of rabbits. AB - Biodegradable common bile duct (CBD) stents are in high clinical demand. Animal experiments concerning the surgical placement of biliary stents made of new materials are being performed more frequently than ever before. However, these animal experiments only use large animals. In this study, a central venous catheterization set was used as a modified stent introducer system in rabbits. A biodegradable Mg-6Zn alloy CBD stent was passed through the duodenal papilla using this stent introducer system. Computed tomography (CT) scanning of the CBD stent in vivo and levels of serum lipase (LPS) were investigated. Twelve rabbits underwent CBD stent insertion and one animal died due to an anesthetic accident. After 3 weeks, when the remaining 11 rabbits were sacrificed, no jaundice or bile leakage was observed. CT scanning of the 11 rabbits suggested that the biodegradable Mg-6Zn stent was successfully placed into the CBD. When the preoperative and postoperative levels of LPS were compared, no statistically significant differences were observed. This new method appears to be feasible and safe for the placement of stents into the CBDs of small animals. This new method can increase the animal number of CBD stent experiment, and improve the quality of experiments. PMID- 24223630 TI - Gene transfer of human neuregulin-1 attenuates ventricular remodeling in diabetic cardiomyopathy rats. AB - Neuregulin-1 (NRG-1) is a cardioactive growth factor released from endothelial cells. However, the effect of NRG-1 on ventricular remodeling in diabetic cardiomyopathy (DCM) remains unclear. The aim of the present study was to investigate the pathophysiological role of NRG-1 in a rat model of DCM. Rat cardiac microvascular endothelial cells (CMECs) were transfected with human NRG-1 (hNRG-1) lentivirus. The hNRG-1 medium was utilized to culture rat cardiomyocytes. The cardiomyocytes were counted with a hemacytometer to determine the proliferation index and Annexin V/propidium iodide double staining was employed to examine the apoptotic rate. A rat model of DCM was induced by an intraperitoneal injection of streptozotocin. The hNRG-1 lentivirus was injected into the myocardium of the DCM model rats. Four weeks after the lentiviral injection, cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Left ventricular sections were stained with Masson's trichrome to investigate the myocardial collagen content. The expression levels of related genes and proteins were analyzed. The results indicated that hNRG-1 conditioned medium stimulated the proliferation and counteracted the apoptosis of cardiomyocytes in vitro. In the rats with DCM, gene transfer of hNRG-1 to the myocardium improved heart function, as indicated by invasive hemodynamic measurements. In addition, hNRG-1 reduced the number of apoptotic cells, decreased the expression of bax and increased the expression of bcl-2 in the myocardium of the DCM model rats. Myocardial fibrosis and type I and III pro-collagen mRNA levels in the myocardium were significantly reduced by hNRG-1. hNRG-1 also increased the expression of phospho-Akt and phospho-eNOS in the myocardium. In conclusion, the gene transfer of hNRG-1 ameliorates cardiac dysfunction in diabetes. Although further studies are required, NRG-1 appears to protect cardiomyocytes against apoptosis and to reduce the extent of myocardial interstitial fibrosis. PMID- 24223631 TI - Clinicopathological observations of colorectal serrated lesions associated with invasive carcinoma and high-grade intraepithelial neoplasm. AB - The aim of this study was to investigate the clinicopathological characteristics of colorectal serrated lesions associated with invasive carcinoma and high-grade intraepithelial neoplasm (HIN), as well as to determine the immunohistochemical expression of MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), K-ras and O6 methylguanine-DNA methyltransferase (MGMT). A total of 5,347 cases diagnosed with colorectal polyp or adenoma were included in this study from October 2002 to September 2009. A total of 16 cases of colorectal serrated lesions associated with invasive carcinoma/HIN were screened. These comprised seven cases of traditional serrated adenoma (TSA) associated with invasive carcinoma and HIN, six cases of sessile serrated adenoma (SSA) associated with invasive carcinoma/HIN and three cases of hyperplastic polyp (HP) associated with invasive carcinoma/HIN. TSA associated with invasive carcinoma/HIN predominantly occurred in the rectum with a clearly serrated structure and ectopic crypts. High-grade dysplasia was observed in filiform TSA, which was more prone to carcinogenesis. SSA associated with invasive carcinoma/HIN mainly occurred in the ileocecal junction, with the SSA serrated glands closely located adjacent to the muscularis mucosa and the basal crypt expanded with inverted T- or L-shaped branches. HPs were observed in three cases in the cancer-adjacent tissues with invasive carcinoma, while a HP-SSA/TSA-carcinoma sequence was found in two cases. Immunohistochemistry showed that MGMT expression was significantly different in the serrated lesion tissues compared with that in cancer tissues (P=0.022), control cancer tissues (P=0.002) and normal colorectal epithelial tissues (P=0.003). TSA and SSA may progress to cancer or directly develop into invasive adenocarcinoma. Filiform TSA easily develops into HIN, followed by infiltration. HP may arise from the cancer-adjacent tissues of the invasive carcinoma, which are closely adjacent to the cancer tissues. Further research is needed to investigate the potential direct involvement of HP in carcinogenesis. PMID- 24223632 TI - Hepatocyte growth factor and basic fibroblast growth factor regulate atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease via the mitogen-activated protein kinase signaling pathway. AB - The aim of this study was to investigate the interrelation between basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), and to explore the possible molecular mechanisms underlying this interrelation. Twenty patients with RHD who were scheduled for valve replacement were divided into two groups, comprising 10 cases with AF and 10 cases with sinus rhythm (SR). Clinical data were collected and a small sample of aseptic left atrial appendage was collected by the surgeon. Hematoxylin and eosin (H&E) and Masson's trichrome-stained sections were used to evaluate the cross-sectional area and level of fibrosis, respectively. The expression levels of bFGF and HGF were assessed using immunohistochemistry. The phosphorylation levels of mitogen activated protein kinase/extracellular signal-regulated kinase 1/2 (MEK1/2), c Jun N-terminal kinase 1/2 (JNK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 in atrial tissue were measured using western blotting. Compared with the SR group, myocardial cell diameter was significantly expanded and there was increased collagen deposition in the AF group (P<0.05). The distribution of bFGF in the AF group was significantly higher than that in the SR group (P<0.05); however, HGF levels were significantly lower in the AF group (P<0.05). The phosphorylation levels of MEK1/2, ERK1/2, JNK1/2 and p38 in the AF group were significantly higher than those in the SR group (P<0.05). The results indicated that bFGF may promote the development of atrial fibrosis, while HGF may function in an opposite manner in patients with AF and RHD. The mitogen-activated protein kinase (MAPK) signaling pathway may be the molecular basis for these roles in atrial fibrosis. PMID- 24223633 TI - Fibrohistiocytoma combined with an aneurysmal bone cyst at T7 in a 63-year-old woman. AB - We present a case of spinal tumor, with fibrohistiocytoma combined with aneurysmal bone cyst (ABC) at the pedicle and transverse process of T7 in a 63 year-old female. ABC is a rare skeletal tumor and spinal ABC is extremely rare. Fibrohistiocytoma is a type of primary benign bone tumor. ABC is also a rare bone tumor that most often occurs in the pelvis. The combined lesion of two primary bone benign tumors is relatively rare in clinic. In addition, fibrohistiocytoma and ABC are widely confused with other giant cell containing tumors of the bone. X-rays, magnetic resonance imaging (MRI) and positron emission tomography computed tomography (PET-CT) scans were performed and assessed. Finally, the diagnosis was confirmed by pathological tests. The patient underwent surgery and had an extremely good recovery. The correct diagnosis of a spine tumor is important when determining the surgical procedure. PMID- 24223634 TI - Effects of dexamethasone on angiotensin II-induced changes of monolayer permeability and F-actin distribution in glomerular endothelial cells. AB - The aim of this study was to investigate the changes in monolayer permeability and F-actin distribution caused by angiotensin II (Ang II)-induced injury in glomerular endothelial cells (GENCs) and the effects of dexamethasone on these changes. GENCs isolated and cultured from Wistar rats were used to examine the changes in monolayer permeability and F-actin distribution induced by Ang II. GENC permeability was evaluated by measuring the diffusion of biotin-conjugated bovine serum albumin (biotin-BSA) across a cell monolayer. The expression levels and distribution of F-actin were assessed by flow cytometry. The biotin-BSA concentrations were measured by capture enzyme-linked immunosorbent assay. Ang II at a concentration of 10 mg/l increased the permeability of the GENC monolayer at 6 h and 12 h (P<0.05 and P<0.01, respectively) and caused F-actin depolymerisation at 6 h and 12 h (P<0.01). The two effects attributed to Ang II were significantly inhibited by dexamethasone treatment (P<0.01). The increased permeability of the GENC monolayer induced by Ang II was significantly correlated with the depolymerisation of F-actin. Dexamethasone abrogated the Ang II-mediated damage to GENCs indicating that it may play an important role in protecting GENCs from injury. PMID- 24223635 TI - Expression and significance of angiopoietin-2 and cyclin D1 in laryngeal squamous cell carcinoma and the correlation with prognosis. AB - The aim of this study was to study the expression of angiopoietin-2 (Ang-2) and the cell cycle protein D1 (cyclin D1) in laryngeal squamous cell carcinoma (SCC), and its clinicopathological meaning. The expression of Ang-2 and cyclin D1 was analyzed in 116 cases of laryngeal SCC, five cases of atypical hyperplasia and five cases of vocal polyp tissues using the immunohistochemical streptavidin perosidase (S-P) method. Ang-2 and cyclin D1 protein expression was not present in 5 cases of atypical hyperplasia or 5 cases of vocal cord polyps. However, the proportions of positive staining in well, moderately and poorly differentiated laryngeal SCC were 40, 66.7 and 100%, respectively, for Ang-2 and 50, 66.7, 100%, respectively, for cyclin D1, and were statistically significant (P<0.05). The expression of Ang-2 was positively correlated with cyclin D1 in the laryngeal SCC (r=0.5042; P<0.05). This showed that the tumor grading and cyclin D1 were independent factors affecting laryngeal SCC patient survival by the Cox regression model of risk factors proportion analysis. Ang-2 is synergistic with cyclin D1 in the development of laryngeal SCC. Ang-2 is associated with the metastasis of lymph nodes. Detection of both Ang-2 and cyclin D1 may possess clinical significance in evaluating the prognosis and guiding the clinical treatment of SCC. PMID- 24223636 TI - Human amniotic epithelial cell feeder layers maintain iPS cell pluripotency by inhibiting endogenous DNA methyltransferase 1. AB - Maintaining induced pluripotent stem (iPS) cells in an undifferentiated, self renewing state during long-term cultivation is, at present, a major challenge. We previously showed that human amniotic epithelial cells (HuAECs) were able to provide a good source of feeder cells for mouse and human embryonic or spermatogonial stem cells; however, the epigenetic mechanisms have not been elucidated. In the present study, mouse embryonic fibroblasts (MEFs) and HuAECs were compared as feeder layers for the long-term culture of human iPS cells. The HuAEC feeders allowed human iPS cells to maintain a high level of alkaline phosphatase (AP) activity and to express key stem cell markers during long-term subculture whereas the MEF feeders did not,. Moreover, the HuAEC feeders significantly affected the cell cycle regulation of the iPS cells, maintaining them in the resting stage and the early stage of DNA synthesis (G0/G1 stage). Furthermore, the CpG islands of the Nanog and Oct4 promoters were hypomethylated, while the Nanog- and Oct4-specific loci exhibited higher levels of histone H3 acetylation and lower levels of H3K27 trimethylation in iPS cells cultured on HuAECs compared with those cultured on MEFs. The DNA methyltransferase 1 (DNMT1) expression in iPS cells cultured on HuAECs was shown to be lower than in those cultured on MEFs. In addition, DNMT1-silenced human iPS cells were able to maintain pluripotency over long-term culture on MEFs. In combination, these results suggest that endogenous DNMT1 expression in human iPS cells may be regulated by HuAEC feeder cells and that Nanog and Oct4 are crucial components required for the maintenance of iPS cells in an undifferentiated, proliferative state, capable of self-renewal. PMID- 24223637 TI - Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro. AB - Quercetin is a hydrophobic agent with potential anticancer activity. The aim of the present study was to observe the effects of quercetin on the proliferation of the breast cancer cell line MCF-7 and the gene expression of survivin. The molecular mechanism underlying the antiproliferative effect of quercetin was also investigated. MCF-7 breast cancer cells were treated with various concentrations of quercetin. The inhibitory effect of quercetin on proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and the inhibition rate was calculated. Cellular apoptosis was detected by immunocytochemistry and survivin mRNA expression levels were observed using reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis was used to analyze changes in the expression levels of survivin protein. Quercetin induced the apoptosis of MCF-7 cells and inhibited the proliferation of the MCF-7 breast cancer cells in a time- and concentration-dependent manner. The mRNA and protein expression levels of survivin were reduced as the concentration of quercetin increased. Quercetin inhibited the growth of MCF-7 cells and promoted apoptosis by inducing G0/ G1 phase arrest. It also regulated the expression of survivin mRNA in MCF-7 cells, which may be the mechanism underlying its antitumor effect. PMID- 24223638 TI - Endoscopic management of blue rubber bleb nevus syndrome: A case report. AB - Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by multiple recurrent vascular malformations, including hemangioma, which primarily locate on the skin and gastrointestinal (GI) tract. The present study reports a 22-year-old female with iron-deficiency anemia and recurrent episodes of melena. The patient also exhibited characteristic venous malformations of the skin. Endoscopy revealed several hemangiomas in the GI tract. The hemangiomas were treated by ligation using a nylon cord, while small blue mucosal polypoid lesions were treated using a sclerosing agent during colonoscopy and double-balloon enteroscopy. The patient was reviewed regularly for three years following surgery and no further bleeding episodes were noted. PMID- 24223639 TI - Computational pharmacological comparison of Salvia miltiorrhiza and Panax notoginseng used in the therapy of cardiovascular diseases. AB - The herb pair comprising Salvia miltiorrhiza (SM) and Panax notoginseng (PN) has been used as a classical formula for cardiovascular diseases (CVDs) in China and in western countries. However, the pharmacology of SM and PN in this herb pair has not been fully elucidated. The aim of this study was to compare the mechanisms of SM and PN at the molecular level for the treatment of CVDs. We used a systems pharmacology approach, integrating ligand clustering, chemical space, docking simulation and network analysis, to investigate these two herbal medicines. The compounds in SM were attached to clusters 2, 3, 5, 6, 8 and 9, while the compounds in PN were attached to clusters 1, 2, 4, 5, 6, 7, 8 and 10. The distributions of chemical space between the compounds from SM and PN were discrete, with the existence of small portions of overlap, and the majority of the compounds did not violate 'Lipinski's rule of five'. Docking indicated that the average number of targets correlated with each compound in SM and PN were 5.0 and 3.6, respectively. The minority nodes in the SM and PN drug-target networks possessed common values of betweenness centrality, closeness centrality, topological coefficients and shortest path length. Furthermore, network analyses revealed that SM and PN exerted different modes of action between compounds and targets. These results suggest that the method of computational pharmacology is able to intuitively trace out the similarities and differences of two herbs and their interaction with targets from the molecular level, and that the combination of two herbs may extend their activities in different potential multidrug combination therapies for CVDs. PMID- 24223640 TI - Serum proteomics analysis and comparisons using iTRAQ in the progression of hepatitis B. AB - The aim of this study was to analyze the changes in serum protein levels in the progression of hepatitis B using isobaric tags for relative and absolute quantitation (iTRAQ) analysis, in addition to comparing the serum protein levels of patients with chronic hepatitis B (CHB), patients with hepatitis B virus induced acute-on-chronic liver failure (HBV-induced ACLF) and normal individuals. Protein analysis was performed on 15 serum samples using iTRAQ. The study population included healthy controls (n=5), patients with CHB (n=5) and patients with HBV-induced ACLF (n=5). Western blotting was used to verify the results in an additional nine serum samples from healthy controls, patients with CHB and patients with HBV-induced ACLF (n=3, respectively). Using iTRAQ analysis, 16 different serum proteins with >=1.5-fold differences in expression levels were identified in the patients with CHB and ACLF compared with the healthy controls. Five of those proteins, C-reactive protein precursor, hemoglobin beta chain variant Hb S-Wake, apolipoprotein J precursor, platelet factor 4 precursor and vitronectin, which demonstrated the greatest differences in their expression levels and the most significant correlation with liver diseases, were subsequently verified using western blotting. The western blotting results were consistent with the results from the iTRAQ. Two of the five proteins are not classified by biological process, and the biological functions of all the proteins in HBV-induced ACLF remain unclear. This preliminary study demonstrated that a correlation between the expression of various serum proteins and the different pathogenetic conditions induced by HBV may exist. The analysis of a larger number of samples is required to identify potential protein biomarkers that may be involved in the pathogenesis and progression of hepatitis B. PMID- 24223641 TI - Effects of propofol on renal ischemia/reperfusion injury in rats. AB - Renal ischemia/reperfusion injury (IRI) is a major cause of acute renal failure. The aim of this study was to investigate whether propofol pretreatment in a rat model protects kidney tissue against IRI. Thirty-two Wistar rats were equally divided into four groups: a sham-operated group, untreated renal IRI group, and low-dose (5 mg/kg) and high-dose (10 mg/kg) propofol-treated groups which were treated with propofol prior to the induction of IRI. The rats were subjected to renal ischemia by bilateral clamping of the pedicles for 50 min, followed by reperfusion. The low-dose and high-dose propofol treatment groups were pretreated via femoral vein injection with a propofol suspension prior to the induction of ischemia/reperfusion. The untreated IRI group showed significantly higher serum creatinine (SCr), blood urea nitrogen (BUN), interleukin 6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), and malondialdehyde (MDA) levels compared with the sham-operated rats. Superoxide dismutase (SOD) levels were significantly reduced following IRI; however, they significantly increased following propofol administration. Bone morphogenetic protein 2 (BMP2) levels were significantly increased in the propofol-treated groups compared with the untreated IRI group. These results suggest that propofol reduces renal oxidative injury and facilitates repair following IRI. Propofol may play a protective role by regulating BMP2 expression in renal IRI. PMID- 24223642 TI - Changes in expression of four molecular marker proteins and one microRNA in mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis patients. AB - The aim of this study was to detect the expression of microRNA-200c and epithelial-mesenchymal transition (EMT) in the mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis (PD) patients, and to investigate the association between microRNA-200c and peritoneal mesothelial cell EMT. Twelve patients who had recently started continuous ambulatory peritoneal dialysis (PD start group) and 16 patients who had been undergoing peritoneal dialysis for >6 months (PD >6 months group) were randomly chosen for the isolation, culture and identification of effluent cells. qPCR and western blot analysis were used to detect the expression levels of microRNA-200c and the levels of four cellular marker proteins, E-cadherin, vimentin, fibronectin (FN) and COL-1, in effluent cells. The results showed that the effluent cells in peritoneal dialysis were peritoneal mesothelial cells. The level of E-cadherin protein expression was significantly lower in the PD >6 months group than in the PD start group, while vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. microRNA-200c in the PD >6 months group was significantly downregulated. The E-cadherin protein expression level was significantly decreased and vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. The level of microRNA-200c was significantly reduced in the PD > 6 months group, suggesting that microRNA-200c may be associated with EMT. PMID- 24223643 TI - Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice. AB - The present study reports the beneficial effects of an anti-mouse interleukin-6 (IL-6) receptor antibody (MR16-1) on neuropathic pain in mice with spinal cord injury (SCI). Following laminectomy, contusion SCI models were produced using an Infinite Horizon (IH)-impactor. MR16-1 was continuously injected for 14 days using Alzet osmotic pumps. A mouse IL-6 ELISA kit was then used to analyze IL-6 levels in the spinal cord tissue between 12 and 72 h after injury. Motor and sensory functions were evaluated each week using the Basso Mouse Scale (BMS), plantar von Frey and thermal threshold tests. Histological examinations were performed 42 days after SCI. Between 24 and 72 h after SCI, the expression levels of IL-6 were significantly decreased in the MR16-1 treated group. Six weeks after surgery, the BMS score of the MR16-1-treated group indicated significant recovery of neurological functions. MR16-1-treated mice in the SCI group exhibited lower paw withdrawal thresholds in the plantar von Frey and thermal tests, which were used to evaluate allodynia. MR16-1 treatment significantly increased the area of Luxol fast blue-stained tissue, representing spared myelin sheaths. These results indicate that the continuous inhibition of IL-6 signaling by MR16-1 between the early and sub-acute phases following SCI leads to neurological recovery and the suppression of hyperalgesia and allodynia. Overall, our data suggest that the inhibition of severe inflammation may be a promising neuroprotective approach to limit secondary injury following SCI and that an anti-IL-6 receptor antibody may have clinical potential for the treatment of SCI. PMID- 24223644 TI - Soluble toll-like receptor 4 reversed attenuating effect of Chinese herbal Xiao Qing-Long-Tang on allergen induced nerve growth factor and thymic stromal lymphopoietin. AB - Xiao-Qing-Long-Tang (XQLT) is known to regulate allergic immune reactions. The aim of this study was to investigate the effects of XQLT on allergen-induced cytokines and associated signaling pathways. An acute allergic mouse model was used to investigate the effects of XQLT on nerve growth factor (NGF) during an allergic reaction, while human pulmonary alveolar epithelial cells (HPAEpiCs) were used to investigate the effects of XQLT on Dermatophagoides pteronyssinus group 2 (Der p 2)-induced NGF, p75 neurotrophin receptor (p75NTR) and thymic stromal lymphopoietin (TSLP) expression. XQLT was demonstrated to inhibit NGF- and p75NTR-related allergic reactions in the mouse model. XQLT also reduced the expression of Toll-like receptor 4 (TLR4) in the lungs of the model mice. XQLT inhibited Der p 2-induced NGF, TSLP and p75NTR expression in the HPAEpiC cell line. The use of recombinant soluble TLR4 (sTLR4) in a competitive assay partially attenuated the inhibitory effect of XQLT on NGF, TSLP and p75NTR expression in HPAEpiC cells. The inhibitory effect of XQLT on the Ser536 phosphorylation of p65 (nuclear factor-kappaB; NF-kappaB), a TLR4-induced factor, was also attenuated by sTLR4. In conclusion, XQLT inhibited Der p allergen induced NGF, p75NTR and TSLP expression. This inhibition was attenuated by sTLR4. The mechanism of action of XQLT may be correlated with TLR4, a primary receptor in the innate immune system. The findings of this study may focus the search for pharmacological targets of XQLT onto TLR4, which is important in the allergen presentation pathway. PMID- 24223645 TI - Monitoring luciferase-labeled human prostate stem cell antigen-expressing tumor growth in a mouse model. AB - The aim of this study was to establish a tumor model in mice with the expression of luciferase (Luc) and human prostate stem cell antigen (PSCA), in order to evaluate the activities of anticancer drugs or vaccines for prostate cancer. RM-1 cells were stably transfected with pcDNA-Luc and pcDNA-PSCA plasmids. The Luc expressing cells were examined using a luminometer and the PSCA-expressing cells were examined using a reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. Male C57BL/6 mice were inoculated subcutaneously with the RM-PSCA/Luc cells, prior to the tumor growth and survival time of the mice being measured, respectively. In vivo bioluminescence imaging was used to detect Luc expression and immunohistochemical analysis was used to detect PSCA expression. Inoculation of the tumor cells into the C57BL/6 mice closely mimicked the tumor growth of prostate cancer. All of the inoculated mice exhibited a detectable tumor within two weeks. Tumor progression was able to be quantitatively monitored following the inoculation of 1*106 RM-PSCA/Luc cells. There was an excellent correlation (R2=0.9849) between the photon counts and tumor volume. The expression of PSCA in tumor tissues was confirmed using immunohistochemical analysis. The Luc and PSCA co-expression tumor model was successfully established in mice, which is likely to accelerate the understanding of the pathogenesis of prostate cancer and facilitate the development of novel antitumor drugs or vaccines for the disease. PMID- 24223646 TI - Assessment of left ventricular dyssynchrony and cardiac function in patients with different pacing modes using real-time three-dimensional echocardiography: Comparison with tissue Doppler imaging. AB - The aim of this study was to evaluate the left ventricular mechanical dyssynchrony (LVMD) and left ventricular dysfunction of patients in AAI, DDD and VVI pacing modes using real-time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI). The results from the RT3DE and TDI were subsequently compared. Twenty patients with sick sinus syndrome (SSS) who had undergone the implantation of a dual-chamber pacemaker were enrolled in this study and the pacemakers were programmed to AAI, DDD and VVI modes, sequentially. The RT3DE and TDI parameters were obtained following pacing for 24 h in each mode. With RT3DE, we measured the systolic dyssynchrony indices, including Tmsv16 SD%, Tmsv12-SD%, Tmsv6-SD%, Tmsv16-Dif%, Tmsv12-Dif% and Tmsv6-Dif%, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF), respectively. With TDI, we measured the standard deviation and the maximal difference in time from the QRS onset to the peak systolic velocity for 12 left ventricular myocardial segments, i.e. Ts-SD and Ts-Dif, respectively. The results showed that the Tmsv16-SD% and Ts-SD in the AAI mode were significantly lower than those in the DDD and VVI modes (P<0.05); however, there were no significant differences between the DDD and VVI modes (P>0.05). The LVEF in the AAI, DDD and VVI modes was 63.1+/-8.9, 58.6+/-11.2 and 57.9+/-7.6%, respectively (P>0.05). There were negative correlations between the LVEF and Tmsv16-SD% (r, -0.651; P<0.001) and Ts-SD (r, 0.649; P<0.0001). A moderate correlation (r, 0.698; P<0.0001) was observed between Tmsv16-SD% and Ts-SD. The concordance rate between Tmsv16-SD% and Ts-SD for detecting LVMD was 76%. This study showed that DDD and VVI pacing modes induced significant LVMD and a reduction in LVEF, unlike the AAI pacing mode. RT3DE and TDI were capable of objectively evaluating LVMD; however, each method had certain faults. At present, there is a lack of a uniform standard for assessing LVMD; therefore, the use of a variety of techniques and indices is necessary in order to comprehensively evaluate LVMD in patients with different cardiac pacing modes. PMID- 24223647 TI - Change in the perioperative blood glucose and blood lactate levels of non diabetic patients undergoing coronary bypass surgery. AB - In the present study, a retrospective analysis of the trends and factors affecting blood glucose and blood lactate levels was carried out for non-diabetic adult patients who had undergone coronary artery bypass graft (CABG) surgery. Between October 2009 and October 2011, 200 non-diabetic adult patients undergoing CABG surgery were examined. Glucose and lactic acid levels were observed successively during surgery [following the induction of anesthesia, cardio pulmonary bypass (CPB), aortic cross-clamping and aortic stop flow infusion], at the end of surgery and after surgery [1, 6, 12, 24 and 48 h after admission to the intensive care unit (ICU)]. The results of blood gas analyses and other related indicators for trend analysis were investigated. The peak blood glucose and blood lactate levels during CPB, as well as other CPB factors, were also analyzed. Following aortic cross-clamping, intraoperative blood glucose and blood lactate levels increased gradually with increasing operative time. Postoperatively, blood glucose and blood lactate levels continued to rise. Blood glucose and blood lactic acid levels during CPB were positively correlated. The blood glucose and blood lactate levels of non-diabetic adult patients undergoing CABG increased gradually with operative time following aortic cross-clamping. Moreover, blood glucose and blood lactate levels were positively correlated with the duration of CPB and duration of aortic cross-clamping. PMID- 24223648 TI - Effects of iodine-125 seeds on the methylation of SFRP2 and P16 in colorectal cancer. AB - The current study investigated the effects of iodine-125 seeds on the gene methylation of SFRP2 and P16 in colorectal cancer. Mouse models of human colorectal cancer were randomly divided into an experimental group (n=25) and a control group (n=25). The control group was implanted with blank seeds (0 MBq) and the experimental group with iodine-125 seeds (14.8 MBq). At 20 days after implantation, the animals were sacrificed. The methylation levels of SFRP2 and P16 were detected using methylation-specific polymerase chain reactions (MSPs). Following iodine-125 seed irradiation, the level of SFRP2 methylation decreased. The methylation index of the experimental group (0.67+/-0.05) was significantly lower than that of the control group (0.84+/-0.07; P<0.05). In the experimental group, 10 samples (40%) displayed methylation in the P16 promoter region compared with 14 (56%) in the control group, which was a significant difference (P<0.05). Iodine-125 seeds induce the downregulation of methylated tumor suppressor gene promoters, thereby inhibiting the proliferation and growth of tumor cells. PMID- 24223649 TI - Staining with methylthioninium chloride for the diagnosis of fungal keratitis. AB - The aim of this study was to investigate the potential efficacy of staining with methylthioninium chloride (MC) for the diagnosis of fungal keratitis. A total of 70 cases of fungal keratitis were included in the study from January 2009 to December 2010. The corneal scraping specimens of the patients were collected and stained with MC or a 10% potassium hydroxide (KOH)-based smear prior to microscopic examination. The staining results were confirmed with fungal culture and strain identification, which are recognized as 'gold standards' for the diagnosis of fungal keratitis. Among the 70 cases of fungal keratitis, 58 cases were positive and the positive rate was 82.86%. MC staining showed a positive rate of 62.86%, with higher levels of sensitivity (70.69%) and specificity (34.61%) compared with staining with the 10% KOH-based smear. The KOH-based smear showed a positive rate of 44.29% (P<0.05), a level of sensitivity of 44.83% (P<0.05) and a specificity of 17.95% (P<0.05). In addition, the MC staining showed false positive and negative rates of 25.00 and 29.31%, respectively, an accuracy index of 5.30% and positive and negative predictive values of 93.18 and 34.61%, respectively. The results indicate that MC staining is a fast and effective method for the early diagnosis of fungal keratitis. PMID- 24223650 TI - Merosin-deficient congenital muscular dystrophy type 1A: A case report. AB - The aim of this study was to characterize the clinical and genetic features of a 4-year-old female with merosin-deficient congenital muscular dystrophy type 1A (MDC1A). MDC1A is the most common form of congenital muscular dystrophy. MDC1A is caused by mutation of the laminin alpha-2 gene (LAMA2), localized to chromosome 6q22-23. Clinical presentation, as well as the results of neuro-imaging, electrophysiology and molecular genetic tests were used to evaluate a patient with MDC1A. The patient exhibited severe hypotonia and marked proximal weakness at 6 months of age, as well as delayed developmental milestones. The serum creatine kinase levels of the patient were elevated at 1,556 IU/l. Magnetic resonance imaging (MRI) showed that the white matter in the frontal, parietal, temporal and occipital lobes was abnormal with low signal intensities on T1 weighted images and high signal intensities on T2-weighted images; however, the cortex was normal. Sequencing of the 65 exons of the LAMA2 revealed a homozygous nonsense mutation in exon 50: a C>T exchange in nucleotide 7147 that resulted in a stop codon (Arg2383X stop). Molecular genetic testing is a reliable method for confirming a diagnosis of MDC1A. When a patient presents with severe congenital hypotonia, muscle weakness, high serum creatine kinase (CK) levels and white matter abnormalities, the evaluation may directly proceed to molecular genetic testing of the LAMA2 gene without performing a muscle biopsy. PMID- 24223651 TI - Correlation between serum cathepsin S and insulin resistance in type 2 diabetes. AB - Cathepsin S (CatS), a proteolytic enzyme, which belongs to the cysteine proteinase family, is associated with atherosclerosis, coronary heart disease, cancer and other diseases. The present study aimed to explore the correlation between serum CatS and insulin resistance (IR) in patients with type 2 diabetes. A total of 51 patients with type 2 diabetes (Group DM) were recruited for this study and 49 healthy individuals were selected as normal controls (Group NC). Blood pressure and body mass index (BMI) were recorded, and serum creatinine, CatS, glycosylated hemoglobin (HbA1c), lipid and insulin levels, and fasting plasma glucose (FPG) levels were measured in all the participants. The homeostatic model assessment index of IR (HOMA-IR) was calculated according to FPG and serum insulin levels. Serum CatS, very low density lipoprotein (VLDL) and triglyceride (TG) levels in Group DM were significantly higher compared with those in Group NC (P=0.000, 0.014 and 0.020, respectively). Significantly positive correlations were identified between CatS levels and VLDL and TG levels, respectively (P<0.05 for both); however, no significant correlations were determined between CatS levels and age, course of disease, blood pressure, cholesterol, BMI, FPG, HbAc1 and HOMA-IR (P>0.05). Further stratification analysis showed that CatS had no association with IR at different HOMA-IR and HbA1c levels. The present study demonstrated that serum CatS, which was significantly increased in patients with type 2 diabetes, had no correlation with IR. This indicates that CatS and IR are independent of each other; however, the precise mechanisms require further investigation. PMID- 24223652 TI - Clinical and pathological analysis of the kidney in patients with hypertensive nephropathy. AB - The aim of the present study was to identify the association between pathological types of kidney and clinical manifestations in patients with hypertensive nephropathy. The blood pressure, fundus, urinalysis test results and renal function changes were analysed in patients who were treated for hypertensive nephropathy. Downward kidney puncture biopsy was performed using a 16G ejection needle with the aid of B ultrasound in 47 cases. The specimens were observed using light microscopy and immunofluorescence. The pathological changes observed in the patients exhibiting symptoms of hypertensive nephropathy varied. The majority of clinical manifestations were benign arteriolar nephrosclerosis, hyaline degeneration of the renal artery and the appearance of a thickened wall of a thickened renal artery wall. Severe cases showed malignant arteriolar nephrosclerosis characterised by fibrinoid necrosis of renal arterioles and intimal hyperplasia. In addition, in the severe cases, fibrinoid necrosis of the afferent arteriole and arcuate artery wall was observed, with severe interlobular artery and arcuate artery myointimal thickening. Renal biopsy in patients with hypertensive nephropathy is safe and feasible. The prognosis and treatment of pathological and clinical disease related to renal pathology is necessary. PMID- 24223653 TI - The effects of Euphorbia hirta on the ultrastructure of the murine liver, kidney and aorta. AB - Euphorbia hirta is widely used in traditional remedies and has been used cross culturally for generations against maladies such as asthma, skin ailments and hypertension. Previous studies have demonstrated that Euphorbia hirta has antibacterial activity, and have also indicated certain antimolluscidal, antimalarial and anti-inflammatory properties, the latter of which have been suggested to be more pronounced than those of the rheumatological drug, etanercept. To date, no studies have identified the anatomical effects of this herb on the organs of test animals. This study aimed to identify the effects of Euphorbia hirta on the ultrastructure of the murine liver, kidney and aorta. A total of 32 adult male Sprague-Dawley rats were divided into four groups; three groups were fed with aqueous extracts of Euphorbia hirta at doses of 1, 10 and 50 mg/kg, respectively, every alternate day for 50 days, while one group served as a control. The animals were later sacrificed and the liver, kidney and aorta harvested for examination by electron microscopy. The aorta showed no ultrastructural changes across the groups. Renal and hepatic tissue from the treated groups demonstrated dose-dependent injuries, which showed architectural damage beginning in the nuclei and spreading outwards. Taking into consideration the properties of Euphorbia hirta that have been described in previous studies, in addition to the results from the present study, it appears that the herb may exhibit similar effects to those of the quinolone group of antibiotics. Further in-depth investigations are required into the potential effects of Euphorbia hirta, deleterious and otherwise. PMID- 24223654 TI - Nerve growth factor exacerbates allergic lung inflammation and airway remodeling in a rat model of chronic asthma. AB - Nerve growth factor (NGF) is critical in the pathogenesis of allergic airway inflammation in vivo and induces proliferation of airway smooth muscle cells and matrix metalloproteinase-9 (MMP-9) expression in vitro. However, the effects of NGF on chronic pulmonary diseases of allergic origin remain unknown. To investigate the effects of NGF on lung inflammation and airway remodeling, 32 Wistar rats were randomly divided into four groups: control, NGF, ovalbumin (OVA) and anti-rat-beta-NGF antibody (anti-NGF). Aerosolized OVA was administered to the rats in the NGF, OVA and anti-NGF groups to generate the asthmatic rat model, and NGF or anti-NGF was administered 3 h prior to OVA inhalation every two days. On day 70, bronchial responsiveness tests, bronchoalveolar lavage (BAL) and cell counting were conducted. The levels of serum OVA-specific immunoglobulin E (IgE) and of T-helper cell type-2 (Th2) cytokines [interleukin (IL)-4 and IL-13] in the BAL fluid were measured by enzyme-linked immunosorbent assay. The expression levels of NGF protein and MMP-9 mRNA, and the activity of MMP-9 in the lungs were detected by western blot analysis, quantitative polymerase chain reaction and gelatin zymography analysis, respectively. Our results showed that NGF significantly increased eosinophilic airway inflammation, persistent airway hyperresponsiveness (AHR), the serum levels of OVA-specific IgE and the levels of Th2 cytokines in the BAL fluid, and also increased the expression levels and activity of MMP-9. However, anti-NGF treatment significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling. The results showed that NGF may have exacerbated the development of airway inflammation, AHR and airway remodeling through a Th2 pathway and by increasing the level of MMP-9 expression. Therefore, anti-NGF is potentially beneficial for preventing and treating patients with asthma. PMID- 24223655 TI - Sulfated modification and anti-tumor activity of laminarin. AB - The aim of this study was to investigate the sulfated modification of laminarin and the changes in structure and antitumor activity. The chlorosulfonic acid pyridine method was applied for sulfated modification. The molecular weights of laminarin and laminarin sulfate (LAMS) were measured by high-performance liquid chromatography (HPLC), and IR and NMR spectra were also recorded. The surface conformations of laminarin and LAMS were observed with a scanning electron microscope. The antitumor activities of the two polysaccharides were also evaluated using an MTT assay. LAMS with a sulfate content of 45.92% and a molecular weight of 16,000 was synthesized. The IR spectra of laminarin and LAMS showed the characteristic absorption peaks of a polysaccharide, and LAMS also had the characteristic absorption peaks of sulfate moieties. The NMR spectra showed that laminarin and LAMS had beta-(1->3) glycosidic bonds forming the main chain, and sulfate substitution was at the hydroxyl groups of C2 and C6. Under the scanning electron microscope, there were clear differences in surface conformation between laminarin and LAMS; laminarin was cloud-like and spongy, while LAMS was block-like and flaky. The MTT results showed that laminarin and LAMS had inhibitory effects on LoVo cell growth, and the antitumor activity of LAMS was higher than that of laminarin at the same concentration. This suggests that sulfated modification was able to change the laminarin structure and markedly enhance the antitumor activity. PMID- 24223656 TI - miR-31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. AB - MicroRNAs (miRNAs) are involved in the pathogenesis of intrahepatic cholangiocarcinoma (ICC). However, the role of microRNA-31 (miR-31) in ICC has yet to be elucidated. In this study, we demonstrated that the expression of miR 31 was significantly upregulated in ICC tissues and the human ICC cell line HCCC 9810, when compared with that in normal adjacent tissues. Bioinformatic analysis and a dual-luciferase reporter assay revealed RAS p21 GTPase activating protein 1 (RASA1) to be a direct target of miR-31 in HCCC-9810 cells. Further investigation showed that the protein expression level of RASA1 was significantly decreased in ICC tissues, suggesting an inverse correlation between miR-31 and RASA1 expression during the tumorigenesis of ICC. Moreover, the forced downregulation of miR-31 by its inhibitor in HCCC-9810 cells significantly inhibited cell proliferation and promoted cell apoptosis. However, when the cells were cotransfected with miR-31 inhibitor and RASA1-specific small interfering RNA (siRNA), these changes were attenuated. Further analysis of the molecular mechanism showed that the activity of the RAS-mitogen-activated protein kinase (MAPK) signaling pathway was significantly decreased in miR-31-downregulated HCCC 8910 cells, while cotransfection with miR-31 inhibitor and RASA1-specific siRNA attenuated this effect. These results indicate that the downregulation of RASA1 by miR-31 promoted cellular proliferation and inhibited cellular apoptosis, partially by upregulating the activity of the RAS-MAPK signaling pathway in ICC. In conclusion, the present study revealed important regulatory functions of miR 31 and RASA1 in ICC, indicating that miR-31 and RASA1 may become promising diagnostic and/or therapeutic targets for ICC. PMID- 24223657 TI - Differential diagnosis of systemic lupus erythematosus and rheumatoid arthritis with complements C3 and C4 and C-reactive protein. AB - The aim of this study was to analyze the changes in complements C3 and C4 and C reactive protein (CRP) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and to evaluate the role of these indices in the differential diagnosis of SLE and RA. The first 347 patients with SLE, 382 patients with RA and 66 patients with erythema nodosum were selected for the measurement of complement and CRP levels in the serum, the erythema nodosum patients were the control group. The roles of the complements and CRP in the differential diagnosis and disease activity evaluation of SLE and RA were analyzed with SPSS 13.0. Complement C3 and C4 levels were significantly reduced in patients with SLE compared with those in the control group. However, in RA patients, the CRP level was increased. In addition, the levels of complements C3 and C4 in patients with SLE were much lower than those in patients with RA and the level of CRP in RA patients was much higher than that in patients with SLE. The reduction of complement C3 levels in SLE patients, and increase of CRP and complement C4 in patients with RA were associated with a higher risk of joint pain, butterfly rash and oral ulcer. These results show that the disease activity of SLE was negatively correlated with complement C3 and C4, and the disease activity of RA was positively correlated with CRP. With the increase in disease activity, the levels of complements C3 and C4 in patients with SLE were gradually reduced and the level of CRP in patients with RA was increased. There were distinctive differences in the levels of complements C3 and C4 and CRP between SLE and RA patients. The differences are useful in disease activity evaluation and the differential diagnosis of the two diseases that have similar symptoms. PMID- 24223658 TI - Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells. AB - Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro. Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro. TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma. PMID- 24223659 TI - Pharmacokinetic comparison of the vasorelaxant compound ferulic acid following the administration of Guanxin II to healthy volunteers and patients with angina pectoris. AB - Coronary heart disease (CHD) is the leading cause of mortality worldwide. The Chinese medicinal formula Guanxin II has been shown to have a favorable effect in the attenuation of angina. The aim of this study was to compare the pharmacokinetics of ferulic acid (FA), which is a vasorelaxant compound present in Guanxin II, in healthy volunteers and patients with angina pectoris following the administration of Guanxin II. Ex vivo experiments were performed in order to investigate the vasorelaxant effect of FA on the human internal mammary artery (IMA) to provide evidence that it is a bioactive component of Guanxin II. Following the oral administration of Guanxin II, the FA levels in the serum were quantified by a simple and rapid high-performance liquid chromatography (HPLC) method. Treatment with FA (10-8-10-3 M) caused a concentration-dependent relaxation of endothelial IMA rings following precontraction with KCl. Statistically significant differences were identified between the pharmaco kinetic parameters Cmax, t1/2alpha, t1/2beta and t1/2Ka of the healthy volunteers and the patients with angina pectoris following the oral administration of Guanxin II. FA is a bioactive compound absorbed from Guanxin II that attenuates angina pectoris, a condition that may modify the pharmacokinetics of FA. Not only do the pharmacokinetic parameters direct the clinical use of Guanxin II, but they may also be useful for exploring the pathology of angina pectoris. PMID- 24223660 TI - Analysis of promoters and CREB/AP-1 binding sites of the human TMEM174 gene. AB - Transmembrane protein 174 (TMEM174) is a type III transmembrane protein with no clear signal peptide. The N and C terminals are located inside the cell. Our previous study demonstrated high expression of TMEM174 in the kidney and its potential involvement in renal cancer based on its capacity to stimulate cell proliferation. However, the mechanism by which TMEM174 promotes proliferation at the transcriptional level remains to be elucidated. In the present study, the TMEM174 promoter region was amplified from whole blood DNA. Six different regions of the regulatory sequences of the TMEM174 promoter region including ~2.5 kb of the upstream region were cloned into the dual luciferase expression vector pGL3 basic. Comparison of the activity of these fragments in dual luciferase reporter assays revealed higher levels of activity for the fragments spanning -186 to +674, -700 to +674, -1,000 to +674 and -2,500 to +1 bp. Lower levels of activity were detected for the fragments spanning -466 to +674 and -890 to +674 bp. The highest activity was detected for the fragment spanning -186 to +674 bp. Electrophoretic mobility shift assay (EMSA) was performed to determine effective transcription factor binding sites. Specific binding of the cyclic-AMP response element binding (CREB) within the TMEM174 gene promoter region was demonstrated, although binding of the activator protein-1 (AP-1) was also detected in this region. In conclusion, these results suggest that the core promoter region of the human TMEM174 gene is located within the region spanning -186 to +674 bp and that the transcription factors CREB and AP-1 are involved in the transcriptional regulation of this gene. PMID- 24223661 TI - 'Expansion in-situ' concept as a new technique for expanding skin and soft tissue. AB - Techniques for expanding skin and soft tissue are widely used to repair damaged areas since they facilitate the provision of new, additional skin tissue with similar quality, texture and color to that surrounding the defective area. Conventional expansion techniques involve placing expanders under the normal skin adjacent to a lesion. However, these techniques may involve additional incisions, complications with blood supply and 'dog-ear' deformities and may result in a low utilization rate of the expanded tissue. When reconstructing small defects that may not be sutured directly, these shortcomings, particularly the requirement to make additional incisions, limit the application of conventional techniques. The current study presents a novel approach to expansion called the 'expansion in situ' technique. In this technique, the lesion is used as the center for expansion and expanders of optimal size are implanted under the lesion and surrounding normal soft tissue. Following expansion, the damaged area is excised directly. In order to avoid poor healing of the incision made during expander implantation, the overlapping suturing of both cut sides is conducted. This enlarges the contact area of both sides of the incision, thereby avoiding incision dehiscence and increasing wound healing during the expansion process. Between August 2006 and July 2011, the expansion in-situ technique was applied in 10 cases involving either nevus excision or scar removal. All 10 cases were treated successfully. Five of the cases were followed up over 1-3 years. The 'expansion in-situ' technique is likely to be useful for avoiding additional incisions and improving the utilization rate of expanded skin flaps. PMID- 24223662 TI - Insulinization: A promising strategy for the treatment of type 2 diabetes mellitus. AB - The aim of the present study was to assess the efficiency of the long-term use of continuous subcutaneous insulin infusion (CSII), a novel regimen known as insulinization, for the treatment of type 2 diabetes mellitus. A total of 150 subjects who fulfilled the diagnostic criteria for type 2 diabetes were included in the study. The patients were divided into eight groups according to the treatment regimens they received and were monitored for 3 months. Insulin doses were adjusted to optimize glycemic control with the simplest possible insulin regimen. The outcomes studied included the time required for glycemic control and insulin dose reduction, the total daily insulin dose, the ratio of patients not requiring the administration of oral antidiabetic drugs (OADs), the rate of hypoglycemia, and hemoglobin A1c (HbA1c) and fasting plasma insulin (FinS) levels. Patients receiving insulinization required less time to achieve optimal glycemic control and insulin decrement compared with patients receiving other treatments. The total daily insulin dose for patients receiving insulinization therapy was 0.23+/-0.07 U/kg/day, which was lower than that in any other group. In patients receiving insulinization, the ratio of patients that did not require OADs (43.3%) and the concentration of FinS A were higher than those in the other groups. Furthermore, insulinization resulted in a greater reduction in HbA1c levels, as well as a reduced incidence of severe hypoglycemia. Insulinization may mimic physiological insulin secretion more effectively than other therapies. This regimen is more efficient and reduces the incidence of hypoglycemia in patients with type 2 diabetes, indicating that it is likely to be a promising treatment strategy for the disease. PMID- 24223663 TI - Precision of coaxial needle placement in computed tomography-guided transthoracic needle biopsy. AB - In the present study, a set of self-designed measurement protocols for the precision of coaxial needle placement (PCNP) was proposed and applied in a computed tomography (CT)-guided transthoracic needle biopsy (TNB) audit of an interventional radiologist to determine if the PCNP was commensurate with the experience of the operator. A total of 102 patients (98 with lung lesions and four with mediastinum lesions) consented to be subjected to CT-guided TNB performed by staff interventional radiologists. The patients were divided into two groups based on appointment date. Group A consisted of the first 51 patients and group B comprised of the latter 51 patients. A set of self-designed measurement protocols for PCNP was proposed, and the PCNP was classified into four grades, from grade 1 (most accurate) to grade 4 (least accurate). PCNPs were independently measured by three staff radiologists who were blind to the grouping. The anatomical features of the lesions were also analyzed between the two groups. A significant difference in the PCNP gained after the first needle placement was identified between the two groups (P=0.003, two-tailed). The number of patients in group B with grade I PCNP (51.0%) was significantly higher than that in group A (21.6%) (P<0.05). The number of patients in group B with grade III PCNP (11.8%) was significantly lower than that in group A (29.4%, P<0.05). The PCNP was observed to be commensurate with the experience of the operator and should be considered as a routine audit index in CT-guided TNB. PMID- 24223664 TI - Inhibitory effects of resistant starch (RS3) as a carrier for stachyose on dextran sulfate sodium-induced ulcerative colitis in C57BL/6 mice. AB - The aim of this study was to determine the effects of resistant starch 3 (RS3) as a carrier for stachyose on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. RS3 microspheres carrying stachyose (RS3 + stachyose) were produced and evaluated as a potentially improved colitis therapy for this study. The body weights of the mice treated with RS3 + stachyose were higher compared with those of DSS-treated control mice. RS3 + stachyose reduced the levels of the serum pro inflammatory cytokines IL-6 and TNF-alpha to a greater extent compared with the same concentration of stachyose combined with ordinary starch (stachyose + starch). Histopathological examination of sections of colon tissues showed that the RS3 + stachyose group recovered well from colitis; however, the tissue sections of the stachyose + starch group presented necrosis to a more serious degree. These results suggest that stachyose with an RS3 carrier has better preventative effects on colitis than stachyose alone in mice. PMID- 24223665 TI - Curcumin enhances the effectiveness of cisplatin by suppressing CD133+ cancer stem cells in laryngeal carcinoma treatment. AB - Chemoresistance is one of the major barriers to chemotherapeutic treatment and it has been established that CD133+ cancer stem cells are responsible for drug resistance in laryngeal carcinoma. In the present study, curcumin and cisplatin were used as a combined treatment to induce the sensitivity of CD133+ cancer stem cells to chemotherapeutic agents and to enhance therapeutic effectiveness. The results revealed that in untreated and cisplatin-treated HEp-2 cell groups, the percentage of CD133+ cells was 4.50 and 6.89%, respectively. However, in the combined treatment group, the percentage of CD133+ cells was markedly reduced to 1.49%, indicating that curcumin may increase the sensitivity of CD133+ cells to cisplatin, leading to the suppression of chemoresistance in HEp-2 cells. Furthermore, the expression of ATP-binding cassette sub-family G member 2 (ABCG2), which is an important gene for chemoresistance, was demonstrated to be reduced in CD133+ cancer stem cells following combined treatment. These results suggest that the combined application of curcumin with chemotherapeutic drugs may be a reliable and effective approach for the treatment of laryngeal carcinoma. PMID- 24223666 TI - Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhibiting the expression of ICAM-1 and IL-18. AB - It has been demonstrated that breviscapine is able to treat coronary disease and reduce the inflammatory response; however, there are no relevant reports concerning its effects on the expression of inflammatory factors in acute lung injury induced by left heart ischemic reperfusion and the underlying mechanisms. In this study, we created a left heart ischemia-reperfusion model in rats to investigate the effects of breviscapine on the expression of interleukin 18 (IL 18) and intercellular adhesion molecule-1 (ICAM-1), as well as to determine the possible mechanisms involved in the protective effects of breviscapine on respiratory function. The left heart ischemia-reperfusion model was created by ligating the anterior descending branch of the coronary artery for 30 mins followed by reperfusion. Rats in the treatment group (TG) were treated with breviscapine (10 mg/kg) and the rats in the control group (CG) received normal saline. Ten rats in the two groups were sacrificed at three points: 30 min after ligating (T1), 30 min after reperfusion (T2) and 60 min after reperfusion (T3). A respiration curve was produced and the arterial partial pressure of oxygen (PaO2) was measured for all rats. Additionally, the expression levels of IL-18 and ICAM 1 were determined and the correlation between IL-18 and ICAM-1 expression in lung tissue was analyzed. The level of IL-18 in peripheral blood and bronchialalveolar lavage fluid (BALF) was also measured. The respiration amplitude was lower and the duration time was shorter in the TG rats than in the CG rats at T1, T2 and T3. The expression levels of IL-18 and ICAM-1 in the TG group were clearly reduced. The level of IL-18 in the peripheral blood and BALF was downregulated following the administration of breviscapine. These results demonstrate that breviscapine inhibits the expression of IL-18 and ICAM-1, thereby protecting the lungs from inflammatory cascade responses. PMID- 24223667 TI - Serum erythropoietin level predicts the prognosis of chronic heart failure with or without anemia. AB - The aim of this study was to explore the correlation of erythropoietin (EPO) with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C reactive protein (hs-CRP) in patients with chronic heart failure (CHF) or CHF complicated with anemia, in addition to its correlation with the prognosis of the patient. A total of 217 CHF patients were enrolled in this study. The patients were graded according to the cardiac function criteria of the New York Heart Association (NYHA). The serum EPO, NT-proBNP and hs-CRP levels of the patients were determined. The patients were followed up for >=24 months. The EPO expression level in patients with NYHA II-IV CHF was significantly higher compared with that in the control group (P<0.05). EPO expression increased with the aggravation of CHF, exhibiting significant differences amongst the various NYHA graded groups (P<0.05). The EPO expression level increased significantly with an increase in NHA grade in addition to the severity of the anemia in the patients with CHF complicated by anemia (P<0.05). In the patients who succumbed (mortality group), the expression level of EPO was significantly higher and the hemoglobin level was significantly lower compared with those of the survival group (P<0.05). The EPO expression levels were elevated in CHF patients and patients with CHF and anemia. The level of expression correlated positively with the severity of CHF as well as that of anemia. Serum EPO measurements were successful in predicting the mortality and re-hospitalization rates of CHF patients at the end point, within two years of follow-up. PMID- 24223668 TI - Evaluation of the detection of 14 high-risk human papillomaviruses with HPV 16 and HPV 18 genotyping for cervical cancer screening. AB - The American Society for Colposcopy and Cervical Pathology (ASCCP) suggests that women >=30 years old, with a negative cytopathological test but a positive high risk (HR) human papillomavirus (HPV) test should undergo HPV 16 and HPV 18 genotyping. If this test is positive, immediate cervical pathology is required. Therefore, the aim of this study was to evaluate the effectiveness and clinical value of testing for 14 HR HPVs with HPV 16 and HPV 18 genotyping for cervical cancer (CC) screening. A total of 424 females from the China-Japan Friendship Hospital were selected and randomly divided into two groups (A and B). All participants underwent two different testing methods: the liquid-based cytology test (LCT) and a HPV DNA test. For the HPV DNA test, participants in group A underwent the hybrid capture II (HC-II) testing method while participants in group B were tested using the quantitative polymerase chain reaction (qPCR; HBRT H14) method. The sensitivity, specificity, positive predictive value and negative predictive value for the detection of cervical intraepithelial neoplasia (CIN) grade II or greater using HBRT-H14 were 96.30, 78.17, 23.21 and 99.68%, respectively. In Group B, compared with other HR HPV types, HPV 16 and HPV 18 infection led to the increased possibility of cervical lesions graded CIN II or higher (8.11 and 51.28%, respectively). A significant difference in the rates of CC and CIN II or higher was observed among women who were i) infected with HPV 16 and/or HPV 18, ii) infected with other HR HPV types and iii) diagnosed as negative for HR HPV infection (chi2=93.976, P=0.0001). In conclusion, HBRT-H14 is applicable for CC screening with the advantage of genotyping for HPV 16 and HPV 18, which may help to improve triage management for women with negative cytology. PMID- 24223669 TI - Damaging alcohol consumption: evidence based prevention on the WHO model can help. PMID- 24223670 TI - The diagnosis of fetal alcohol syndrome. AB - BACKGROUND: The estimated prevalence of fetal alcohol syndrome (FAS) is 8 for every 1000 live births. FAS has serious, lifelong consequences for the affected children and their families. A variety of professionals deal with persons who have FAS, including pediatricians, general practitioners, neurologists, gynecologists, psychiatrists, and psychotherapists. Early diagnosis is important so that the affected children can receive the support they need in a protective environment. METHODS: A multidisciplinary guideline group has issued recommendations for the diagnosis of FAS after assessment of the available scientific evidence. This information was derived from pertinent literature (2001 2011) retrieved by a systematic search in PubMed and the Cochrane Library, along with the US-American and Canadian guidelines and additional literature retrieved by a manual search. RESULTS: Of the 1383 publications retrieved by the searches, 178 were analyzed for the evidence they contained. It was concluded that the fully-developed clinical syndrome of FAS should be diagnosed on the basis of the following criteria: Patients must have at least one growth abnormality, e.g., short stature, as well as all three characteristic facial abnormalities-short palpebral fissure length, a thin upper lip, and a smooth philtrum. They must also have at least one diagnosed structural or functional abnormality of the central nervous system, e.g., microcephaly or impaired executive function. Confirmation of intrauterine exposure to alcohol is not obligatory for the diagnosis. CONCLUSION: Practical, evidence-based criteria have now been established for the diagnosis of the fully-developed FAS syndrome. More research is needed in order to enable uniform, evidence-based diagnostic assessment of all fetal alcohol spectrum disorders and optimize supportive measures for the children affected by them. PMID- 24223672 TI - Which side is affected? PMID- 24223671 TI - Alcohol-related aggression-social and neurobiological factors. AB - BACKGROUND: Alcohol-related aggression and violence are a widespread cause of personal suffering with high socioeconomic costs. In 2011, nearly one in three violent acts in Germany was committed under the influence of alcohol (31.8%). The link between alcohol consumption and aggression is promoted by various interacting factors. METHODS: In this review, based on a selective search for pertinent literature in PubMed, we analyze and summarize information from original articles, reviews, and book chapters about alcohol and aggression and discuss the neurobiological basis of aggressive behavior. RESULTS: Aggression is promoted both by the cognitive deficits arising in connection with acute or chronic alcohol use and by prior experience of violence in particular situations where alcohol was drunk. Only a minority of persons who drink alcohol become aggressive. On the other hand, alcohol abuse and dependence together constitute the second most commonly diagnosed cause of suicide (15-43%). Current research indicates that the individual tendency toward alcohol-induced aggression depends not just on neurobiological factors, but also on personal expectations of the effects of alcohol, on prior experience of violent conflicts, and on the environmental conditions of early childhood, especially social exclusion and discrimination. Gene-environment interactions affecting the serotonergic and other neurotransmitter systems play an important role. Potential (but not yet adequately validated) therapeutic approaches involve reinforcing cognitive processes or pharmacologically modulating serotonergic neurotransmission (and other target processes). CONCLUSION: Alcohol-related aggression has manifold social and neurobiological causes. Specific treatments must be tested in controlled trials. PMID- 24223673 TI - Cochrane analysis on betahistine omitted. PMID- 24223674 TI - Postural vertigo in older persons. PMID- 24223675 TI - Multiple psychovegetative symptoms. PMID- 24223676 TI - In reply. PMID- 24223677 TI - Patterns and Predictors of Mental Healthcare Utilization in Schools and other Service Sectors among Adolescents at Risk for Depression. AB - This study examined racial/ethnic and socioeconomic differences in service utilization across sectors (specialty mental health, school, primary care) for youth at risk of depression. Our sample included 362 adolescents who were enrolled in a larger project examining the effects of an indicated school-based depression prevention program. Service use across sectors mirrored national trends and previous research findings in which the education sector was most frequently utilized for mental health services. Race/ethnicity was significantly associated with parent-reported specialty mental health service utilization, even when controlling for other predictors of use. The study also suggests that racial disparities in service access generally appear to be reduced through the availability of education sector mental health services. Socioeconomic status was not associated with service use in any sector when controlling for other predictors. Parent-child agreement was moderate for report of specialty mental health service use and low for report of use of services within the education and primary care sectors. PMID- 24223678 TI - Computational Fluid Dynamics Simulations of Hemodynamics in Plaque Erosion. AB - PURPOSE: We investigated whether local hemodynamics were associated with sites of plaque erosion and hypothesized that patients with plaque erosion have locally elevated WSS magnitude in regions where erosion has occurred. METHODS: We generated 3D, patient-specific models of coronary arteries from biplane angiographic images in 3 human patients with plaque erosion diagnosed by optical coherence tomography (OCT). Using computational fluid dynamics, we simulated pulsatile blood flow and calculated both wall shear stress (WSS) and oscillatory shear index (OSI). We also investigated anatomic features of plaque erosion sites by examining branching and local curvature in x-ray angiograms of barium-perfused autopsy hearts. RESULTS: Neither high nor low magnitudes of mean WSS were associated with sites of plaque erosion. OSI and local curvature were also not associated with erosion. Anatomically, 8 of 13 hearts had a nearby bifurcation upstream of the site of plaque erosion. CONCLUSIONS: This study provides preliminary evidence that neither hemodynamics nor anatomy are predictors of plaque erosion, based upon a very unique dataset. Our sample sizes are small, but this dataset suggests that high magnitudes of wall shear stress, one potential mechanism for inducing plaque erosion, are not necessary for erosion to occur. PMID- 24223679 TI - Two new species of Undifilum, fungal endophytes of Astragalus (locoweeds) in the United States. AB - New species of Undifilum, from locoweeds Astragalus lentiginosus Vitman and Astragalus mollissimus Torr., are described using morphological characteristics and molecular phylogenetic analyses as Undifilum fulvum Baucom & Creamer sp. nov. and Undifilum cinereum Baucom & Creamer sp. nov. Fungi were isolated from dried plants of A. lentiginosus var. araneosus, diphysus, lentiginosus, and wahweapensis collected from Arizona, Oregon, and Utah, USA, and A. mollissimus var. biglovii, earleii, and mollissimus collected from New Mexico, Oklahoma, and Texas, USA. Endophytic fungi from Astragalus locoweeds were compared to Undifilum oxytropis isolates obtained from dried plant material of Oxytropis lamberteii from New Mexico and Oxytropis sericea from Arizona, Colorado, New Mexico, Utah, and Wyoming. Extremely slow growth in vitro was observed for all, and conidia, if present, were ellipsoid with transverse septa. However, in vitro color, growth on four different media, and conidium size differed between fungi from Astragalus spp. and U. oxytropis. Neighbor-joining analyses of internal transcribed spacer (ITS) region and glyceraldehyde-3-phosphate dehydrogenase (GPD) gene sequences revealed that U. fulvum and U. cinereum formed a clade distinct from U. oxytropis. This was supported by neighbor-joining analyses of results generated from random amplified polymorphic DNA (RAPD) fragments using two different primers. PMID- 24223692 TI - Reversal learning and associative memory impairments in a BACHD rat model for Huntington disease. AB - Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the Huntingtin (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently found a similar emergence of non motor and motor deficits in BACHD rats carrying the human full length mutated HTT (97 CAG-CAA repeats). We evaluated cognitive performance in reversal learning and associative memory tests in different age cohorts of BACHD rats. Male wild type (WT) and transgenic (TG) rats between 2 and 12 months of age were tested. Learning and strategy shifting were assessed in a cross-maze test. Associative memory was evaluated in different fear conditioning paradigms (context, delay and trace). The possible confound of a fear conditioning phenotype by altered sensitivity to a 'painful' stimulus was assessed in a flinch jump test. In the cross maze, 6 months old TG rats showed a mild impairment in reversal learning. In the fear conditioning tasks, 4, 6 and 12 months old TG rats showed a marked reduction in contextual fear conditioning. In addition, TG rats showed impaired delay conditioning (9 months) and trace fear conditioning (3 months). This phenotype was unlikely to be affected by a change in 'pain' sensitivity as WT and TG rats showed no difference in their threshold response in the flinch-jump test. Our results suggest that BACHD rats have a profound associative memory deficit and, possibly, a deficit in reversal learning as assessed in a cross maze task. The time course for the emergence of these symptoms (i.e., before the occurrence of motor symptoms) in this rat model for HD appears similar to the time course in patients. These data suggest that BACHD rats may be a useful model for preclinical drug discovery. PMID- 24223693 TI - Evaluating the pharmacological mechanism of Chinese medicine Si-Wu-Tang through multi-level data integration. AB - Si-Wu-Tang (SWT) is a Traditional Chinese Medicine (TCM) formula widely used for the treatments of gynecological diseases. To explore the pharmacological mechanism of SWT, we incorporated microarray data of SWT with our herbal target database TCMID to analyze the potential activity mechanism of SWT's herbal ingredients and targets. We detected 2,405 differentially expressed genes in the microarray data, 20 of 102 proteins targeted by SWT were encoded by these DEGs and can be targeted by 2 FDA-approved drugs and 39 experimental drugs. The results of pathway enrichment analysis of the 20 predicted targets were consistent with that of 2,405 differentially expressed genes, elaborating the potential pharmacological mechanisms of SWT. Further study from a perspective of protein-protein interaction (PPI) network showed that the predicted targets of SWT function cooperatively to perform their multi-target effects. We also constructed a network to combine herbs, ingredients, targets and drugs together which bridges the gap between SWT and conventional medicine, and used it to infer the potential mechanisms of herbal ingredients. Moreover, based on the hypothesis that the same or similar effects between different TCM formulae may result from targeting the same proteins, we analyzed 27 other TCM formulae which can also treat the gynecological diseases, the subsequent result provides additional insight to understand the potential mechanisms of SWT in treating amenorrhea. Our bioinformatics approach to detect the pharmacology of SWT may shed light on drug discovery for gynecological diseases and could be utilized to investigate other TCM formulae as well. PMID- 24223694 TI - Urinary exosomal microRNAs in incipient diabetic nephropathy. AB - MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR 155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication. PMID- 24223695 TI - Vitamin A transport and the transmembrane pore in the cell-surface receptor for plasma retinol binding protein. AB - Vitamin A and its derivatives (retinoids) play diverse and crucial functions from embryogenesis to adulthood and are used as therapeutic agents in human medicine for eye and skin diseases, infections and cancer. Plasma retinol binding protein (RBP) is the principal and specific vitamin A carrier in the blood and binds vitamin A at 1:1 ratio. STRA6 is the high-affinity membrane receptor for RBP and mediates cellular vitamin A uptake. STRA6 null mice have severely depleted vitamin A reserves for vision and consequently have vision loss, even under vitamin A sufficient conditions. STRA6 null humans have a wide range of severe pathological phenotypes in many organs including the eye, brain, heart and lung. Known membrane transport mechanisms involve transmembrane pores that regulate the transport of the substrate (e.g., the gating of ion channels). STRA6 represents a new type of membrane receptor. How this receptor interacts with its transport substrate vitamin A and the functions of its nine transmembrane domains are still completely unknown. These questions are critical to understanding the molecular basis of STRA6's activities and its regulation. We employ acute chemical modification to introduce chemical side chains to STRA6 in a site-specific manner. We found that modifications with specific chemicals at specific positions in or near the transmembrane domains of this receptor can almost completely suppress its vitamin A transport activity. These experiments provide the first evidence for the existence of a transmembrane pore, analogous to the pore of ion channels, for this new type of cell-surface receptor. PMID- 24223696 TI - Five-year prognosis after mild to moderate ischemic stroke by stroke subtype: a multi-clinic registry study. AB - BACKGROUND AND PURPOSE: Mild to moderate ischemic stroke is a common presentation in the outpatient setting. Among the various subtypes of stroke, lacunar infarction (LI) is generally very common. Currently, little is known about the long-term prognosis and factors associated with the prognosis between LI and non LI. This study aims to compare the risk of death and acute cardiovascular events between patients with LI and non-LI, and identify potential risk factors associated with these outcomes. METHODS: A total of 710 first-ever ischemic stroke patients (LI: 474, non-LI: 263) from 18 clinics were recruited consecutively from 2003 to 2004. They were prospectively followed-up until the end of 2008. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazards regression. RESULTS: After a 5-year follow up, 54 deaths and 96 acute cardiovascular events occurred. Recurrent stroke was the most common cause of death (19 cases, 35.18%) and new acute cardiovascular events (75 cases, 78.13%). There were no significant differences between patients with LI and non-LI in their risks of death, new cardiovascular events, and recurrent stroke after adjusting for age, sex, hypertension, diabetes, cardiac diseases, body mass index, dyslipidemia, smoking, alcohol consumption, ADL dependence, and depressive symptoms. Among the modifiable risk factors, diabetes, hypertension, ADL dependency, and symptoms of depression were independent predictors of poor outcomes in patients with LI. In non-LI patients, however, no modifiable risk factors were detected for poor outcomes. CONCLUSION: Long-term outcomes did not differ significantly between LI and non-LI patients. Detecting and managing vascular risk factors and depression as well as functional rehabilitation may improve the prognoses of LI patients. PMID- 24223697 TI - Semantic annotation of mutable data. AB - Electronic annotation of scientific data is very similar to annotation of documents. Both types of annotation amplify the original object, add related knowledge to it, and dispute or support assertions in it. In each case, annotation is a framework for discourse about the original object, and, in each case, an annotation needs to clearly identify its scope and its own terminology. However, electronic annotation of data differs from annotation of documents: the content of the annotations, including expectations and supporting evidence, is more often shared among members of networks. Any consequent actions taken by the holders of the annotated data could be shared as well. But even those current annotation systems that admit data as their subject often make it difficult or impossible to annotate at fine-enough granularity to use the results in this way for data quality control. We address these kinds of issues by offering simple extensions to an existing annotation ontology and describe how the results support an interest-based distribution of annotations. We are using the result to design and deploy a platform that supports annotation services overlaid on networks of distributed data, with particular application to data quality control. Our initial instance supports a set of natural science collection metadata services. An important application is the support for data quality control and provision of missing data. A previous proof of concept demonstrated such use based on data annotations modeled with XML-Schema. PMID- 24223698 TI - Computer-aided diagnosis of skin lesions using conventional digital photography: a reliability and feasibility study. AB - BACKGROUND: Computer-aided diagnosis (CADx) software that provides a second opinion has been widely used to assist physicians with various tasks. In dermatology, however, CADx has been mostly limited to melanoma or melanocytic skin cancer diagnosis. The frequency of non-melanocytic skin cancers and the accessibility of regular digital macrographs have raised interest in developing CADx for broader applications. OBJECTIVES: To investigate the feasibility of using CADx to diagnose both melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. METHODS: This study was approved by an institutional review board, and the requirement to obtain informed consent was waived. In total, 769 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed and used to develop a CADx system. Conventional and new color-related image features were developed to classify the lesions as benign or malignant using support vector machines (SVMs). The performance of CADx was compared with that of dermatologists. RESULTS: The clinicians' overall sensitivity, specificity, and accuracy were 83.33%, 85.88%, and 85.31%, respectively. New color correlation and principal component analysis (PCA) features improved the classification ability of the baseline CADx (p = 0.001). The estimated area under the receiver operating characteristic (ROC) curve (Az) of the proposed CADx system was 0.949, with a sensitivity and specificity of 85.63% and 87.65%, respectively, and a maximum accuracy of 90.64%. CONCLUSIONS: We have developed an effective CADx system to classify both melanocytic and non-melanocytic skin lesions using conventional digital macrographs. The system's performance was similar to that of dermatologists at our institute. Through improved feature extraction and SVM analysis, we found that conventional digital macrographs were feasible for providing useful information for CADx applications. The new color-related features significantly improved CADx applications for skin cancer. PMID- 24223699 TI - A computational model associating learning process, word attributes, and age of acquisition. AB - We propose a new model-based approach linking word learning to the age of acquisition (AoA) of words; a new computational tool for understanding the relationships among word learning processes, psychological attributes, and word AoAs as measures of vocabulary growth. The computational model developed describes the distinct statistical relationships between three theoretical factors underpinning word learning and AoA distributions. Simply put, this model formulates how different learning processes, characterized by change in learning rate over time and/or by the number of exposures required to acquire a word, likely result in different AoA distributions depending on word type. We tested the model in three respects. The first analysis showed that the proposed model accounts for empirical AoA distributions better than a standard alternative. The second analysis demonstrated that the estimated learning parameters well predicted the psychological attributes, such as frequency and imageability, of words. The third analysis illustrated that the developmental trend predicted by our estimated learning parameters was consistent with relevant findings in the developmental literature on word learning in children. We further discuss the theoretical implications of our model-based approach. PMID- 24223700 TI - Irreversible electroporation ablation (IRE) of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated. AB - BACKGROUND: Irreversible electroporation (IRE) is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. "Learnability" and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively collected database study evaluates the learning curve of IRE. METHODS: Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1(st) 50 patients treated), B (2(nd) 50) and C (3(rd) 50 patients treated) chronologically and analyzed for outcomes. RESULTS: A total of 167 IRE procedures were performed, with a majority being liver(39.5%) and pancreatic(35.5%) lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9 vs 3 cm,p=0.001), more numerous lesions (3.2 vs 2.2,p=0.07), more vascular invasion(p=0.001), underwent more associated procedures(p=0.001) and had longer operative times(p<0.001). Despite this, they had similar complication and high grade complication rates(p=0.24). Attributable morbidity rate was 13.3%(total 29.3%) and high-grade complications were seen in 4.19%(total 12.6%). Pancreatic lesions(p=0.001) and laparotomy(p=0.001) were associated with complications. CONCLUSION: The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable learning curve of at least 5 cases to become proficient. PMID- 24223701 TI - Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas. AB - Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype. PMID- 24223702 TI - Standardization of size, shape and internal structure of spinal cord images: comparison of three transformation methods. AB - Functional fluorescence imaging has been widely applied to analyze spatio temporal patterns of cellular dynamics in the brain and spinal cord. However, it is difficult to integrate spatial information obtained from imaging data in specific regions of interest across multiple samples, due to large variability in the size, shape and internal structure of samples. To solve this problem, we attempted to standardize transversely sectioned spinal cord images focusing on the laminar structure in the gray matter. We employed three standardization methods, the affine transformation (AT), the angle-dependent transformation (ADT) and the combination of these two methods (AT+ADT). The ADT is a novel non-linear transformation method developed in this study to adjust an individual image onto the template image in the polar coordinate system. We next compared the accuracy of these three standardization methods. We evaluated two indices, i.e., the spatial distribution of pixels that are not categorized to any layer and the error ratio by the leave-one-out cross validation method. In this study, we used neuron-specific marker (NeuN)-stained histological images of transversely sectioned cervical spinal cord slices (21 images obtained from 4 rats) to create the standard atlas and also to serve for benchmark tests. We found that the AT+ADT outperformed other two methods, though the accuracy of each method varied depending on the layer. This novel image standardization technique would be applicable to optical recording such as voltage-sensitive dye imaging, and will enable statistical evaluations of neural activation across multiple samples. PMID- 24223703 TI - Prevalence of neurobehavioral, social, and emotional dysfunction in patients treated for childhood craniopharyngioma: a systematic literature review. AB - BACKGROUND: Craniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas. MATERIALS AND METHODS: A systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in >= 10 patients were included. RESULTS: Of the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts. CONCLUSIONS: Neurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders. PMID- 24223704 TI - Semantics, syntax or neither? A case for resolution in the interpretation of N500 and P600 responses to harmonic incongruities. AB - The processing of notes and chords which are harmonically incongruous with their context has been shown to elicit two distinct late ERP effects. These effects strongly resemble two effects associated with the processing of linguistic incongruities: a P600, resembling a typical response to syntactic incongruities in language, and an N500, evocative of the N400, which is typically elicited in response to semantic incongruities in language. Despite the robustness of these two patterns in the musical incongruity literature, no consensus has yet been reached as to the reasons for the existence of two distinct responses to harmonic incongruities. This study was the first to use behavioural and ERP data to test two possible explanations for the existence of these two patterns: the musicianship of listeners, and the resolved or unresolved nature of the harmonic incongruities. Results showed that harmonically incongruous notes and chords elicited a late positivity similar to the P600 when they were embedded within sequences which started and ended in the same key (harmonically resolved). The notes and chords which indicated that there would be no return to the original key (leaving the piece harmonically unresolved) were associated with a further P600 in musicians, but with a negativity resembling the N500 in non-musicians. We suggest that the late positivity reflects the conscious perception of a specific element as being incongruous with its context and the efforts of musicians to integrate the harmonic incongruity into its local context as a result of their analytic listening style, while the late negativity reflects the detection of the absence of resolution in non-musicians as a result of their holistic listening style. PMID- 24223705 TI - Regulation of autophagy via PERK-eIF2alpha effectively relieve the radiation myelitis induced by iodine-125. AB - Radiation myelitis is the most serious complication in clinical radiotherapy for spinal metastases. We previously showed that (125)I brachytherapy induced apoptosis of spinal cord neurons accompanied by autophagy. In this study, we further investigated the mechanism by which (125)I radiation triggered autophagy in neural cells. We found that autophagy induced by (125)I radiation was involved in endoplasmic reticulum (ER) stress and mainly dependent on PERK-eIF2alpha pathway. The expressions of LC3II, ATG12 and PI3K were significantly suppressed in PERK knockout neural cells. Meanwhile, the expressions of phosphorylated-Akt s473 and caspase3/8 all significantly increased in neural cells transfected with a PERK siRNA and which enhanced apoptosis of neurons after (125)I radiation. The results were consistent with that by MTT and Annexin-FITC/PT staining. In animal model of banna pigs with radiation myelitis caused by (125)I brachytherapy, we have successfully decreased PERK expression by intrathecal administration of the lentivirus vector. The apoptosis rate was significantly higher than that in control group and which deteriorated radiation myelitis of banna pigs. Thus, autophagy caused by (125)I radiation was mainly as an attempt of cell survival at an early stage, but it would be a self-destructive process and promoted the process of apoptosis and necrosis radiated by (125)I for more than 72 hours. The study would be useful and helpful to maximize efficiency of radiation therapy in clinical therapy. PMID- 24223706 TI - Dihydromyricetin reduced Bcl-2 expression via p53 in human hepatoma HepG2 cells. AB - Dihydromyricetin (DHM) is a major active ingredient of flavonoids compounds. It exhibited anticancer activity and induced apoptosis in human hepatocellular carcinoma HepG2 cells according to our previous data. In this study, we investigated whether p53 is involved in DHM-triggered viability inhibition and apoptosis induction in cancer cells. MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide] assay was employed to evaluate the viability of HepG2 cells after DHM treatment. Meanwhile, p53 small interfering RNA (siRNA) was adopted to silence p53 expression. Protein level of p53 and Bax/Bcl-2 were evaluated by western blot analysis. Cell counting assay showed that DHM inhibited HepG2 cell growth effectively in a time- and dose-dependent manner. P53 expression was significantly increased after DHM treatment, whereas Bcl-2 was reduced potently. Furthermore, after co-treatment with Pifithrin-alpha (PFT alpha, p53 inhibitor), Bcl-2 expression was reversed. The expression of Bax was no significant change, which was also observed after p53 silence. These findings defined and supported a novel function that DHM could induce human hepatocellular carcinoma HepG2 cells apoptosis by up-regulating Bax/Bcl-2 expression via p53 signal pathway. PMID- 24223707 TI - Energy expenditure compared to physical activity measured by accelerometry and self-report in adolescents: a validation study. AB - BACKGROUND: Physical inactivity is responsible for 5.3 million deaths annually worldwide. To measure physical activity energy expenditure, the doubly labeled water (DLW) method is the gold standard. However, questionnaires and accelerometry are more widely used. We compared physical activity measured by accelerometer and questionnaire against total (TEE) and physical activity energy expenditure (PAEE) estimated by DLW. METHODS: TEE, PAEE (TEE minus resting energy expenditure) and body composition were measured using the DLW technique in 25 adolescents (16 girls) aged 13 years living in Pelotas, Brazil. Physical activity was assessed using the Actigraph accelerometer and by self-report. Physical activity data from accelerometry and self-report were tested against energy expenditure data derived from the DLW method. Further, tests were done to assess the ability of moderate-to-vigorous intensity physical activity (MVPA) to predict variability in TEE and to what extent adjustment for fat and fat-free mass predicted the variability in TEE. RESULTS: TEE varied from 1,265 to 4,143 kcal/day. It was positively correlated with physical activity (counts) estimated by accelerometry (rho = 0.57; p = 0.003) and with minutes per week of physical activity by questionnaire (rho = 0.41; p = 0.04). An increase of 10 minutes per day in moderate-to-vigorous intensity physical activity (MVPA) relates to an increase in TEE of 141 kcal/day. PAEE was positively correlated with accelerometry (rho = 0.64; p = 0.007), but not with minutes per week of physical activity estimated by questionnaire (rho = 0.30; p = 0.15). Physical activity by accelerometry explained 31% of the vssariability in TEE. By incorporating fat and fat-free mass in the model, we were able to explain 58% of the variability in TEE. CONCLUSION: Objectively measured physical activity significantly contributes to the explained variance in both TEE and PAEE in Brazilian youth. Independently, body composition also explains variance in TEE, and should ideally be taken into account when using accelerometry to predict energy expenditure values. PMID- 24223708 TI - The involvement of PI3K-mediated and L-VGCC-gated transient Ca2+ influx in 17beta estradiol-mediated protection of retinal cells from H2O2-induced apoptosis with Ca2+ overload. AB - Intracellular calcium concentration ([Ca(2+)]i) plays an important role in regulating most cellular processes, including apoptosis and survival, but its alterations are different and complicated under diverse conditions. In this study, we focused on the [Ca(2+)]i and its control mechanisms in process of hydrogen peroxide (H2O2)-induced apoptosis of primary cultured Sprague-Dawley (SD) rat retinal cells and 17beta-estradiol (betaE2) anti-apoptosis. Fluo-3AM was used as a Ca(2+) indicator to detect [Ca(2+)]i through fluorescence-activated cell sorting (FACS), cell viability was assayed using MTT assay, and apoptosis was marked by Hoechst 33342 and annexin V/Propidium Iodide staining. Besides, PI3K activity was detected by Western blotting. Results showed: a) 100 MUM H2O2 induced retinal cell apoptosis occurred at 4 h after H2O2 stress and increased in a time-dependent manner, but [Ca(2+)]i increased earlier at 2 h, sustained to 12 h, and then recovered at 24 h after H2O2 stress; b) 10 MUM betaE2 treatment for 0.5-24 hrs increased cell viability by transiently increasing [Ca(2+)]i, which appeared only at 0.5 h after betaE2 application; c) increased [Ca(2+)]i under 100 uM H2O2 treatment for 2 hrs or 10 uM betaE2 treatment for 0.5 hrs was, at least partly, due to extracellular Ca(2+) stores; d) importantly, the transiently increased [Ca(2+)]i induced by 10 uM betaE2 treatment for 0.5 hrs was mediated by the phosphatidylinositol-3-kinase (PI3K) and gated by the L-type voltage-gated Ca(2+) channels (L-VGCC), but the increased [Ca(2+)]i induced by 100 uM H2O2 treatment for 2 hrs was not affected; and e) pretreatment with 10 uM betaE2 for 0.5 hrs effectively protected retinal cells from apoptosis induced by 100 uM H2O2, which was also associated with its transient [Ca(2+)]i increase through L VGCC and PI3K pathway. These findings will lead to better understanding of the mechanisms of betaE2-mediated retinal protection and to exploration of the novel therapeutic strategies for retina degeneration. PMID- 24223709 TI - A novel piggyBac transposon inducible expression system identifies a role for AKT signalling in primordial germ cell migration. AB - In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development. PMID- 24223710 TI - Is the United States still dominant in the global pharmaceutical innovation network? AB - The dramatic growth of research and development activities in the pharmaceutical sector in emerging economies raises the question of whether the United States still keeps its dominant role in the global pharmaceutical innovation landscape. This paper focuses on investigating the role of the United States in global pharmaceutical innovation, and differs from previous studies by shifting attention to a network analytic perspective to track the global distribution of pharmaceutical inventions. Our sample is composed of key patents covering all new drugs approved by the Food and Drug Administration between 1996 and 2010. The results show that the United States still dominates in the global pharmaceutical innovation network, especially when it comes to essential core inventions. However, the United States shows a slightly decreasing prominence in the networks of either total new drugs or New Molecular Entity (NME) drugs in the time period 2006-2010 as compared to previous time periods, revealed by subtle traces of network centralities. PMID- 24223711 TI - Elevation of matrix metalloproteinase-9 level in cerebrospinal fluid of tick borne encephalitis patients is associated with IgG extravassation and disease severity. AB - BACKGROUND: Tick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV), is an infectious disease involving the central nervous system (CNS). The pathogenesis of CNS injury has not been clearly demonstrated. Matrix metalloproteinase-9 (MMP-9) and some cytokines, such as interleukin 6 (IL-6), may play important roles in the disruption of the blood-brain barrier (BBB) and the pathogenesis of TBE. METHODS: 72 cerebrospinal fluid (CSF) samples were collected from TBE patients in north eastern China. IgG levels in CSF and serum were compared and MMP-9 and IL-6 levels were evaluated by ELISA. The correlation between the elevated MMP-9 levels and IgG extravasation, disease severity, and neuroinflammation was analyzed. RESULTS: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression. Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement. Four of the 72 patients, the ones who died, presented with high CSF MMP-9 levels. CONCLUSIONS: In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity. PMID- 24223712 TI - Comparative metagenomics of anode-associated microbiomes developed in rice paddy field microbial fuel cells. AB - In sediment-type microbial fuel cells (sMFCs) operating in rice paddy fields, rice-root exudates are converted to electricity by anode-associated rhizosphere microbes. Previous studies have shown that members of the family Geobacteraceae are enriched on the anodes of rhizosphere sMFCs. To deepen our understanding of rhizosphere microbes involved in electricity generation in sMFCs, here, we conducted comparative analyses of anode-associated microbiomes in three MFC systems: a rice paddy-field sMFC, and acetate- and glucose-fed MFCs in which pieces of graphite felt that had functioned as anodes in rice paddy-field sMFC were used as rhizosphere microbe-bearing anodes. After electric outputs became stable, microbiomes associated with the anodes of these MFC systems were analyzed by pyrotag sequencing of 16S rRNA gene amplicons and Illumina shotgun metagenomics. Pyrotag sequencing showed that Geobacteraceae bacteria were associated with the anodes of all three systems, but the dominant Geobacter species in each MFC were different. Specifically, species closely related to G. metallireducens comprised 90% of the anode Geobacteraceae in the acetate-fed MFC, but were only relatively minor components of the rhizosphere sMFC and glucose-fed MFC, whereas species closely related to G. psychrophilus were abundantly detected. This trend was confirmed by the phylogenetic assignments of predicted genes in shotgun metagenome sequences of the anode microbiomes. Our findings suggest that G. psychrophilus and its related species preferentially grow on the anodes of rhizosphere sMFCs and generate electricity through syntrophic interactions with organisms that excrete electron donors. PMID- 24223713 TI - Disentangling woodland caribou movements in response to clearcuts and roads across temporal scales. AB - Although prey species typically respond to the most limiting factors at coarse spatiotemporal scales while addressing biological requirements at finer scales, such behaviour may become challenging for species inhabiting human altered landscapes. We investigated how woodland caribou, a threatened species inhabiting North-American boreal forests, modified their fine-scale movements when confronted with forest management features (i.e. clearcuts and roads). We used GPS telemetry data collected between 2004 and 2010 on 49 female caribou in a managed area in Quebec, Canada. Movements were studied using a use--availability design contrasting observed steps (i.e. line connecting two consecutive locations) with random steps (i.e. proxy of immediate habitat availability). Although caribou mostly avoided disturbances, individuals nonetheless modulated their fine-scale response to disturbances on a daily and annual basis, potentially compromising between risk avoidance in periods of higher vulnerability (i.e. calving, early and late winter) during the day and foraging activities in periods of higher energy requirements (i.e. spring, summer and rut) during dusk/dawn and at night. The local context in which females moved was shown to influence their decision to cross clearcut edges and roads. Indeed, although females typically avoided crossing clearcut edges and roads at low densities, crossing rates were found to rapidly increase in greater disturbance densities. In some instance, however, females were less likely to cross edges and roads as densities increased. Females may then be trapped and forced to use disturbed habitats, known to be associated with higher predation risk. We believe that further increases in anthropogenic disturbances could exacerbate such behavioural responses and ultimately lead to population level consequences. PMID- 24223714 TI - Incorporation of phosphatase inhibitor in culture prompts growth initiation of isolated non-growing oocytes. AB - In vitro folliculogenesis of primordial and early preantral follicles is necessary for increment of reproductive efficiency in domestic animals, humans and endangered species. Recent study in phosphatase and tensin homolog (Pten) knockout mice has revealed that this phosphatase acts as an inhibitory factor in follicle activation of primordial pool with the resultant inhibition of oocyte growth. To test in vitro effect of a phosphatase inhibitor on growth initiation of isolated non-growing oocytes in neonatal ovaries, we applied a specific inhibitor (bpV (HOpic)) for PTEN in culturing system. Non-growing oocytes isolated from the ovaries of newborn BDF1 (C57BL/6 * DBA/2) pups were divided to four culture groups. Five days after culture, the oocytes in 14 MUmol/l bpV only, 14 MUmol/l bpV plus 100 ng/ml Kit Ligand (KL), and 100 ng/ml KL groups showed significantly (P<0.05) growth (19.3 +/- 0.55, 25.8 +/- 0.53 and 21.6 +/- 0.29 MUm, respectively) compared with that of the control (no additive) (16.9 +/- 0.53 MUm). In addition, western blotting in those groups showed enhanced expression of phosphorylated Akt. In conclusion, we clearly demonstrate that isolated non growing oocytes develop in phosphatase inhibitor, especially to PTEN, incorporated culturing system, and show first as we know that oocytes with zona Pellucidae can be obtained in vitro from isolated non-growing oocytes. PMID- 24223715 TI - Infection related never events in pediatric patients undergoing spinal fusion procedures in United States: prevalence and predictors. AB - OBJECTIVE: To examine the prevalence and predictors of infection related never events (NE) associated with spinal fusion procedures (SFP) in children (age < = 18 years) in the United States. METHODS: We performed a retrospective analysis of the Nationwide Inpatient Sample for the years 2004 to 2008. All pediatric hospitalizations that underwent SFP were selected for analysis. The main outcomes measures include occurrence of certain NE's. The association between the occurrence of a NE and factors (patient & hospital related) were examined using multivariable logistic regression analysis. RESULTS: Of 56,465 hospitalizations, 61.7% occurred among females. The average age was 13.7 y and two-thirds were whites. The major insurance payer was private insurance (67.4%). About 82% of all hospitalizations occurred on an elective basis. Teaching hospitals accounted for a majority of hospitalizations (87.9%). Two-thirds were posterior fusion techniques, 52.3% had underlying musculoskeletal deformities, and the most frequently present co-morbid conditions (CMC) included paralysis (10.9%), chronic pulmonary disease (9.7%), and fluid/electrolyte disorders (7.6%). Overall rate of occurrence of a NE was 4.8%. Post-operative pneumonia was the most frequently occurring NE (2.9%). Female gender (OR = 0.78) and elective admissions (OR = 0.66) were associated with lower risk of NE occurrence. Medicaid coverage (OR = 1.46), primary diagnosis of other acquired deformities (OR = 1.82), spinal cord injury (OR = 6.94), other nervous system disorders (OR = 2.84) were associated with higher risk of NE occurrence. Among CMC, those with chronic blood loss anemia (OR = 2.57), coagulopathy (OR = 1.97), depression (OR = 2), drug abuse (OR = 3.71), fluid/electrolyte disorders (OR = 2.62), neurological disorders (OR = 1.72), paralysis (OR = 1.75), renal failure (OR = 5.45), and weight loss (OR = 4.61) were risk factors for higher odds of a NE occurrence. Hospital teaching status, region, hospital size, and patient race did not influence the occurrence of NE. CONCLUSION: The never events examined in the current study occurred in 4.8% of children hospitalized with SFP. Certain predictors of NE are identified in this study. PMID- 24223716 TI - Distribution and ecophysiology of calanoid copepods in relation to the oxygen minimum zone in the eastern tropical atlantic. AB - Oxygen minimum zones (OMZs) affect distribution patterns, community structure and metabolic processes of marine organisms. Due to the prominent role of zooplankton, especially copepods, in the marine carbon cycle and the predicted intensification and expansion of OMZs, it is essential to understand the effects of hypoxia on zooplankton distribution and ecophysiology. For this study, calanoid copepods were sampled from different depths (0-1800 m) at eight stations in the eastern tropical Atlantic (3 degrees 47'N to 18 degrees S) during three expeditions in 2010 and 2011. Their horizontal and vertical distribution was determined and related to the extent and intensity of the OMZ, which increased from north to south with minimum O2 concentrations (12.7 umol kg(-1)) in the southern Angola Gyre. Calanoid copepod abundance was highest in the northeastern Angola Basin and decreased towards equatorial regions as well as with increasing depth. Maximum copepod biodiversity was observed in the deep waters of the central Angola Basin. Respiration rates and enzyme activities were measured to reveal species-specific physiological adaptations. Enzyme activities of the electron transport system (ETS) and lactate dehydrogenase (LDH) served as proxies for aerobic and anaerobic metabolic activity, respectively. Mass-specific respiration rates and ETS activities decreased with depth of occurrence, consistent with vertical changes in copepod body mass and ambient temperature. Copepods of the families Eucalanidae and Metridinidae dominated within the OMZ. Several of these species showed adaptive characteristics such as lower metabolic rates, additional anaerobic activity and diel vertical migration that enable them to successfully inhabit hypoxic zones. PMID- 24223717 TI - Assessing the status of wild felids in a highly-disturbed commercial forest reserve in Borneo and the implications for camera trap survey design. AB - The proliferation of camera-trapping studies has led to a spate of extensions in the known distributions of many wild cat species, not least in Borneo. However, we still do not have a clear picture of the spatial patterns of felid abundance in Southeast Asia, particularly with respect to the large areas of highly disturbed habitat. An important obstacle to increasing the usefulness of camera trap data is the widespread practice of setting cameras at non-random locations. Non-random deployment interacts with non-random space-use by animals, causing biases in our inferences about relative abundance from detection frequencies alone. This may be a particular problem if surveys do not adequately sample the full range of habitat features present in a study region. Using camera-trapping records and incidental sightings from the Kalabakan Forest Reserve, Sabah, Malaysian Borneo, we aimed to assess the relative abundance of felid species in highly-disturbed forest, as well as investigate felid space-use and the potential for biases resulting from non-random sampling. Although the area has been intensively logged over three decades, it was found to still retain the full complement of Bornean felids, including the bay cat Pardofelis badia, a poorly known Bornean endemic. Camera-trapping using strictly random locations detected four of the five Bornean felid species and revealed inter- and intra-specific differences in space-use. We compare our results with an extensive dataset of >1,200 felid records from previous camera-trapping studies and show that the relative abundance of the bay cat, in particular, may have previously been underestimated due to the use of non-random survey locations. Further surveys for this species using random locations will be crucial in determining its conservation status. We advocate the more wide-spread use of random survey locations in future camera-trapping surveys in order to increase the robustness and generality of inferences that can be made. PMID- 24223718 TI - Estimating leaf area index in Southeast Alaska: a comparison of two techniques. AB - The relationship between canopy structure and light transmission to the forest floor is of particular interest for studying the effects of succession, timber harvest, and silviculture prescriptions on understory plants and trees. Indirect measurements of leaf area index (LAI) estimated using gap fraction analysis with linear and hemispheric sensors have been commonly used to assess radiation interception by the canopy, although the two methods often yield inconsistent results. We compared simultaneously obtained measurements of LAI from a linear ceptometer and digital hemispheric photography in 21 forest stands on Prince of Wales Island, Alaska. We assessed the relationship between these estimates and allometric LAI based on tree diameter at breast height (LAIDBH). LAI values measured at 79 stations in thinned, un-thinned controls, old-growth and clearcut stands were highly correlated between the linear sensor (AccuPAR) and hemispheric photography, but the latter was more negatively biased compared to LAIDBH. In contrast, AccuPAR values were more similar to LAIDBH in all stands with basal area less than 30 m(2)ha(-1). Values produced by integrating hemispheric photographs over the zenith angles 0-75 degrees (Ring 5) were highly correlated with those integrated over the zenith angles 0-60 degrees (Ring 4), although the discrepancies between the two measures were significant. On average, the AccuPAR estimates were 53% higher than those derived from Ring 5, with most of the differences in closed canopy stands (unthinned controls and old-growth) and less so in clearcuts. Following typical patterns of canopy closure, AccuPAR LAI values were higher in dense control stands than in old-growth, whereas the opposite was derived from Ring 5 analyses. Based on our results we advocate the preferential use of linear sensors where canopy openness is low, canopies are tall, and leaf distributions are clumped and angles are variable, as is common in the conifer forests of coastal Alaska. PMID- 24223719 TI - Trabecular evidence for a human-like gait in Australopithecus africanus. AB - Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb. PMID- 24223720 TI - The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions. AB - Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR) is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls), by means of the Experience Sampling Method (ESM). Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately. PMID- 24223721 TI - Crystal structure of a four-layer aggregate of engineered TMV CP implies the importance of terminal residues for oligomer assembly. AB - BACKGROUND: Crystal structures of the tobacco mosaic virus (TMV) coat protein (CP) in its helical and disk conformations have previously been determined at the atomic level. For the helical structure, interactions of proteins and nucleic acids in the main chains were clearly observed; however, the conformation of residues at the C-terminus was flexible and disordered. For the four-layer aggregate disk structure, interactions of the main chain residues could only be observed through water-mediated hydrogen bonding with protein residues. In this study, the effects of the C-terminal peptides on the interactions of TMV CP were investigated by crystal structure determination. METHODOLOGY/PRINCIPAL FINDINGS: The crystal structure of a genetically engineered TMV CP was resolved at 3.06 A. For the genetically engineered TMV CP, a six-histidine (His) tag was introduced at the N-terminus, and the C-terminal residues 155 to 158 were truncated (N-His TMV CP(19)). Overall, N-His-TMV CP(19) protein self-assembled into the four-layer aggregate form. The conformations of residues Gln36, Thr59, Asp115 and Arg134 were carefully analyzed in the high radius and low radius regions of N-His-TMV CP(19), which were found to be significantly different from those observed previously for the helical and four-layer aggregate forms. In addition, the aggregation of the N-His-TMV CP(19) layers was found to primarily be mediated through direct hydrogen-bonding. Notably, this engineered protein also can package RNA effectively and assemble into an infectious virus particle. CONCLUSION: The terminal sequence of amino acids influences the conformation and interactions of the four-layer aggregate. Direct protein-protein interactions are observed in the major overlap region when residues Gly155 to Thr158 at the C terminus are truncated. This engineered TMV CP is reassembled by direct protein protein interaction and maintains the normal function of the four-layer aggregate of TMV CP in the presence of RNA. PMID- 24223722 TI - Initiation of psychotropic medication after partner bereavement: a matched cohort study. AB - BACKGROUND: Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. AIMS: To describe initiation of psychotropic medication in the first year after partner bereavement. METHODS: In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. RESULTS: The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. CONCLUSION: Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use. PMID- 24223724 TI - Late diagnosis and entry to care after diagnosis of human immunodeficiency virus infection: a country comparison. AB - BACKGROUND: Testing for HIV infection and entry to care are the first steps in the continuum of care that benefit individual health and may reduce onward transmission of HIV. We determined the percentage of people with HIV who were diagnosed late and the percentage linked into care overall and by demographic and risk characteristics by country. METHODS: Data were analyzed from national HIV surveillance systems. Six countries, where available, provided data on two late diagnosis indicators (AIDS diagnosis within 3 months of HIV diagnosis, and AIDS diagnosis within 12 months before HIV diagnosis) and linkage to care (>= 1 CD4 or viral load test result within 3 months of HIV diagnosis) for people diagnosed with HIV in 2009 or 2010 (most recent year data were available). PRINCIPAL FINDINGS: The percentage of people presenting with late stage disease at HIV diagnosis varied by country, overall with a range from 28.7% (United States) to 8.8% (Canada), and by transmission categories. The percentage of people diagnosed with AIDS who had their initial HIV diagnosis within 12 months before AIDS diagnosis varied little among countries, except the percentages were somewhat lower in Spain and the United States. Overall, the majority of people diagnosed with HIV were linked to HIV care within 3 months of diagnosis (more than 70%), but varied by age and transmission category. CONCLUSIONS: Differences in patterns of late presentation at HIV diagnosis among countries may reflect differences in screening practices by providers, public health agencies, and people with HIV. The percentage of people who received assessments of immune status and viral load within 3 months of diagnosis was generally high. PMID- 24223723 TI - The HIV-1 Tat protein induces the activation of CD8+ T cells and affects in vivo the magnitude and kinetics of antiviral responses. AB - T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies induced by Tat immunization protect from progression to AIDS and reverse signs of immune activation in HIV-infected patients suggesting a role of Tat in T cell dysfunctionality. The Tat protein of HIV-1 is known to induce, in vitro, the activation of CD4(+) T lymphocytes, but its role on CD8(+) T cells and how these effects modulate, in vivo, the immune response to pathogens are not known. To characterize the role of Tat in T cell hyperactivation and dysfunction, we examined the effect of Tat on CD8(+) T cell responses and antiviral immunity in different ex vivo and in vivo models of antigenic stimulation, including HSV infection. We demonstrate for the first time that the presence of Tat during priming of CD8(+) T cells favors the activation of antigen-specific CTLs. Effector CD8(+) T cells generated in the presence of Tat undergo an enhanced and prolonged expansion that turns to a partial dysfunctionality at the peak of the response, and worsens HSV acute infection. Moreover, Tat favors the development of effector memory CD8(+) T cells and a transient loss of B cells, two hallmarks of the chronic immune activation observed in HIV-infected patients. Our data provide evidence that Tat affects CD8(+) T cell responses to co-pathogens and suggest that Tat may contribute to the CD8(+) T cell hyperactivation observed in HIV-infected individuals. PMID- 24223725 TI - Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2. AB - OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 * 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 * 10( 18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis. PMID- 24223726 TI - Disentangling detoxification: gene expression analysis of feeding mountain pine beetle illuminates molecular-level host chemical defense detoxification mechanisms. AB - The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle. PMID- 24223727 TI - Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans. AB - Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc 1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID- 24223728 TI - Importance of hydrophobic cavities in allosteric regulation of formylglycinamide synthetase: insight from xenon trapping and statistical coupling analysis. AB - Formylglycinamide ribonucleotide amidotransferase (FGAR-AT) is a 140 kDa bi functional enzyme involved in a coupled reaction, where the glutaminase active site produces ammonia that is subsequently utilized to convert FGAR to its corresponding amidine in an ATP assisted fashion. The structure of FGAR-AT has been previously determined in an inactive state and the mechanism of activation remains largely unknown. In the current study, hydrophobic cavities were used as markers to identify regions involved in domain movements that facilitate catalytic coupling and subsequent activation of the enzyme. Three internal hydrophobic cavities were located by xenon trapping experiments on FGAR-AT crystals and further, these cavities were perturbed via site-directed mutagenesis. Biophysical characterization of the mutants demonstrated that two of these three voids are crucial for stability and function of the protein, although being ~20 A from the active centers. Interestingly, correlation analysis corroborated the experimental findings, and revealed that amino acids lining the functionally important cavities form correlated sets (co-evolving residues) that connect these regions to the amidotransferase active center. It was further proposed that the first cavity is transient and allows for breathing motion to occur and thereby serves as an allosteric hotspot. In contrast, the third cavity which lacks correlated residues was found to be highly plastic and accommodated steric congestion by local adjustment of the structure without affecting either stability or activity. PMID- 24223729 TI - NF-kappaB repressing factor inhibits chemokine synthesis by peripheral blood mononuclear cells and alveolar macrophages in active pulmonary tuberculosis. AB - NF-kappaB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-kappaB targeting genes, including iNOS, IFN-beta and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP 10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL 8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. PMID- 24223730 TI - Mitochondrial and nuclear genes-based phylogeography of Arvicanthis niloticus (Murinae) and sub-Saharan open habitats pleistocene history. AB - A phylogeographic study was conducted on the Nile grass rat, Arvicanthis niloticus, a rodent species that is tightly associated with open grasslands from the Sudano-Sahelian regions. Using one mitochondrial (cytochrome b) and one nuclear (intron 7 of Beta Fibrinogen) gene, robust patterns were retrieved that clearly show that (i) the species originated in East Africa concomitantly with expanding grasslands some 2 Ma, and (ii) four parapatric and genetically well defined lineages differentiated essentially from East to West following Pleistocene bioclimatic cycles. This strongly points towards allopatric genetic divergence within savannah refuges during humid episodes, then dispersal during arid ones; secondary contact zones would have then stabilized around geographic barriers, namely, Niger River and Lake Chad basins. Our results pertinently add to those obtained for several other African rodent as well as non-rodent species that inhabit forests, humid zones, savannahs and deserts, all studies that now allow one to depict a more comprehensive picture of the Pleistocene history of the continent south of the Sahara. In particular, although their precise location remains to be determined, at least three Pleistocene refuges are identified within the West and Central African savannah biome. PMID- 24223731 TI - Two new species of the enigmatic Leptokoenenia (Eukoeneniidae: Palpigradi) from Brazil: first record of the genus outside intertidal environments. AB - Two new species of Leptokoenenia Conde 1965 (Eukoeneniidae: Palpigradi), Leptokoenenia pelada sp. nov. and Leptokoenenia thalassophobica sp. nov., are described based on both male and female specimens collected in iron ore caves from the Brazilian Amazon. This is the first record of the genus for the Americas. Furthermore, a new combination is stated for Eukoenenia gallii based on its morphology. PMID- 24223732 TI - Fatty acid synthase as a factor required for exercise-induced cognitive enhancement and dentate gyrus cellular proliferation. AB - Voluntary running is a robust inducer of adult hippocampal neurogenesis. Given that fatty acid synthase (FASN), the key enzyme for de novo fatty acid biosynthesis, is critically involved in proliferation of embryonic and adult neural stem cells, we hypothesized that FASN could mediate both exercise-induced cell proliferation in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhancement of spatial learning and memory. In 20 week-old male mice, voluntary running-induced hippocampal-specific upregulation of FASN was accompanied also by hippocampal-specific accumulation of palmitate and stearate saturated fatty acids. In experiments addressing the functional role of FASN in our experimental model, chronic intracerebroventricular (i.c.v.) microinfusions of C75, an irreversible FASN inhibitor, and significantly impaired exercise-mediated improvements in spatial learning and memory in the Barnes maze. Unlike the vehicle-injected mice, the C75 group adopted a non-spatial serial escape strategy and displayed delayed escape latencies during acquisition and memory tests. Furthermore, pharmacologic blockade of FASN function with C75 resulted in a significant reduction, compared to vehicle treated controls, of the number of proliferative cells in the DG of running mice as measured by immunoreactive to Ki 67 in the SGZ. Taken together, our data suggest that FASN plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis. PMID- 24223733 TI - Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of Echovirus: implication for post-virus islet autoimmunity. AB - Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4 infected islets. These findings suggest that the extent of the epidemic associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets. PMID- 24223734 TI - Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer. AB - BACKGROUND: Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR 205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR 483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis. PMID- 24223735 TI - N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression. AB - BACKGROUND: N-MYC down-regulated-like (NDL) proteins interact with the Gbeta subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. METHODOLOGY/PRINCIPAL FINDINGS: Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down regulation) confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele) mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. CONCLUSION/SIGNIFICANCE: NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients. PMID- 24223736 TI - Effect of hydrophobic acrylic versus hydrophilic acrylic intraocular lens on posterior capsule opacification: meta-analysis. AB - PURPOSE: This meta-analysis aims to evaluate the differences in performance of posterior capsular opacification (PCO) between hydrophobic acrylic intraocular lens (IOLs) and hydrophilic acrylic IOLs. SETTING: Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China. DESIGN: Systematic review of randomized controlled trials (RCTs) or meta-analysis. METHODS: An electronic literature search was performed using the PubMed, EMBASE and Cochrane Library database before May in 2013 to identify prospective RCTs comparing hydrophobic acrylic IOLs and hydrophilic acrylic IOLs in patients after phacoemulsification with IOL implantation with a follow-up time of at least 1 year. Pertinent studies were selected by meeting predefined criteria and reviewed systematically by meta-analysis. The PCO scores and YAG capsulotomy rate, as indicator of PCO, were measured and discussed in a meta analysis. Standardized mean differences (SMD), relative risk ratio (RR), and the pooled estimates were computed according to a random effect model or fixed effect model. RESULTS: Nine prospective RCTs involving 861 eyes were included in the current meta-analysis. The hydrophobic acrylic IOLs were favored and the pooled SMD of PCO severity was 1.72 (95% confidence interval (CI), 0.20 to 1.23, P = 0.0002) and 1.79 (95% CI, 0.95 to 2.64, P<0.0001) with 1-year follow-up and 2 year follow-up respectively. The pooled RR of Nd:YAG laser capsulotomy rates at postoperative 2-year follow-up was 6.96 (95% CI, 3.69 to 13.11, P<0.00001) comparing hydrophilic acrylic IOLs with hydrophobic acrylic IOLs. CONCLUSIONS: Compared with hydrophilic acrylic IOLs, the hydrophobic acrylic IOLs showed superior reduction in rates of PCO and laser capsulotomy in 2-year follow-up. More RCTs with standard methods for longer follow-up are needed to validate the association. PMID- 24223737 TI - Helicobacter pylori protein JHP0290 binds to multiple cell types and induces macrophage apoptosis via tumor necrosis factor (TNF)-dependent and independent pathways. AB - Activated macrophages at the sub-mucosal space play a major role in generating innate immune responses during H. pylori infection. Final disease outcome largely depends on how H. pylori and bacterium-derived products modulate macrophage responses. Here, we report that JHP0290, a functionally unknown protein from H. pylori, regulates macrophage functions. Recombinant purified JHP0290 (rJHP0290) had the ability to bind to several cell types including macrophages, human gastric epithelial cell lines, human monocyte-derived dendritic cells (MoDC) and human neutrophils. Exposure to rJHP0290 induced apoptosis in macrophages concurrent with release of proinflammatory cytokine tumor necrosis factor (TNF). A mutant strain of H. pylori disrupted in the jhp0290 gene was significantly impaired in its ability to induce apoptosis and TNF in macrophages confirming the role of endogenous protein in regulating macrophage responses. Intracellular signaling involving Src family of tyrosine kinases (SFKs) and ERK MAPK were required for rJHP0290-induced TNF release and apoptosis in macrophages. Furthermore, rJHP0290-induced TNF release was partly dependent on activation of nuclear transcription factor-kappaB (NF-kappaB). Neutralizing antibodies against TNF partially blocked rJHP0290-induced macrophage apoptosis indicating TNF independent pathways were also involved. These results provide mechanistic insight into the potential role of the protein JHP0290 during H. pylori associated disease development. By virtue of its ability to induce TNF, an acid suppressive proinflammatory cytokine and induction of macrophage apoptosis, JHP0290 possibly helps in persistent survival of the bacterium inside the stomach. PMID- 24223738 TI - Plesiomonas shigelloides infection in Southeast China. AB - BACKGROUND: Plesiomonas shigelloides can cause gastroenteritis and extra intestinal diseases in humans. However, the prevalence of P. shigelloides infections has not been investigated in China. METHODS: Consecutive fecal specimens from outpatients with acute diarrhea and non-diarrheal patients at nine sentinel hospitals in southeast China were collected from March 2010 to May 2012. Bacterial pathogens were detected by culture, and P. shigelloides isolates were subjected to antimicrobial susceptibility testing. We also retrospectively reviewed the hospital microbiology laboratory and infection-control databases for all P. shigelloides isolates identified from 2001-2012 at our institution in addition to data on the patients' clinical and demographic characteristics. RESULTS: A total of 3,536 outpatients with acute diarrhea were enrolled in the study. P. shigelloides was isolated from 104 (2.9%) patients and accounted for 7.3% of bacterial isolates. Single-pathogen infections with P. shigelloides were present in 76 (73.1%) patients. No strain of P. shigelloides was isolated from the 478 non-diarrheal patients. Based on 444,684 nonfecal specimens, eight patients developed P. shigelloides-related extra-intestinal infections over the 12-year period. All eight patients had underlying diseases, including four with biliary tract diseases and three with liver diseases. Six cases were classified as nosocomial, and five cases were polymicrobial. P. shigelloides was sensitive to most antimicrobial drugs, except ampicillin. CONCLUSIONS: In southeast China, P. shigelloides has significant clinical relevance, although the isolation rate is low. PMID- 24223739 TI - Adaptive dynamics of extortion and compliance. AB - Direct reciprocity is a mechanism for the evolution of cooperation. For the iterated prisoner's dilemma, a new class of strategies has recently been described, the so-called zero-determinant strategies. Using such a strategy, a player can unilaterally enforce a linear relationship between his own payoff and the co-player's payoff. In particular the player may act in such a way that it becomes optimal for the co-player to cooperate unconditionally. In this way, a player can manipulate and extort his co-player, thereby ensuring that the own payoff never falls below the co-player's payoff. However, using a compliant strategy instead, a player can also ensure that his own payoff never exceeds the co-player's payoff. Here, we use adaptive dynamics to study when evolution leads to extortion and when it leads to compliance. We find a remarkable cyclic dynamics: in sufficiently large populations, extortioners play a transient role, helping the population to move from selfish strategies to compliance. Compliant strategies, however, can be subverted by altruists, which in turn give rise to selfish strategies. Whether cooperative strategies are favored in the long run critically depends on the size of the population; we show that cooperation is most abundant in large populations, in which case average payoffs approach the social optimum. Our results are not restricted to the case of the prisoners dilemma, but can be extended to other social dilemmas, such as the snowdrift game. Iterated social dilemmas in large populations do not lead to the evolution of strategies that aim to dominate their co-player. Instead, generosity succeeds. PMID- 24223740 TI - Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. AB - TRIAL DESIGN: Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA) but with many contraindications and potential side effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. METHODS: One hundred and sixty infants (gestational age <= 34 weeks) with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80) or ibuprofen (n = 80). After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. RESULT: The ductus was closed in 65 (81.2%) infants of the paracetamol group compared with 63 (78.8%) of the ibuprofen group. The 95% confidence interval of the difference between these groups was [-0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. CONCLUSION: This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-12002177. PMID- 24223741 TI - Branched-chain amino acids ameliorate fibrosis and suppress tumor growth in a rat model of hepatocellular carcinoma with liver cirrhosis. AB - PURPOSE: Recent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model. METHODS: Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. RESULTS: The mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of alpha-smooth muscle actin, vascular endothelial growth factor, p-beta-catenin, p-p38 mitogen activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. CONCLUSIONS: BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level. PMID- 24223742 TI - Serum copeptin and cortisol do not accurately predict sickle cell anaemia vaso occlusive crisis as C-reactive protein. AB - OBJECTIVE: This study assessed the diagnostic performance and prognostic properties of C-reactive protein (CRP), copeptin and cortisol in individuals with sickle cell anaemia (SCA). DESIGN: Prospective case-control study. METHODS: Sixty consecutive SCA subjects (18-40 years) comprising 30 subjects in the steady state and 30 subjects in vaso-occlusive crisis (VOC) were recruited into this study. Thirty (30) apparently healthy individuals with HbAA genotype served as controls. ELISA was used for the determination of serum levels of copeptin, CRP and cortisol. Data obtained were statistically analyzed using the Student's t-test and Mann Whitney U as appropriate and P<0.05 was considered significant. RESULTS: SCA subjects in VOC had significantly lower copeptin level and significantly higher CRP level compared with controls. However, serum levels of copeptin, cortisol and CRP were significantly higher in SCA subjects in VOC compared with SCA subjects in steady state. Furthermore, CRP had the widest Area under the ROC curve (AUROC) than copeptin and cortisol. No significant difference was observed in the levels of copeptin, CRP and cortisol when SCA subjects in VOC who were hospitalized for less <= 5 days were compared with subjects who had longer stays. CONCLUSION: It could be concluded that C-reactive protein has a superior diagnostic performance for vaso-occlusive crisis in individuals with sickle cell anaemia and that C-reactive protein, cortisol and copeptin are not good prognostic markers in SCA subjects in vaso-occlusive crisis. PMID- 24223743 TI - Physical activity, smoking, and alcohol consumption in association with incidence of type 2 diabetes among middle-aged and elderly Chinese men. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease worldwide. The prevalence of T2DM is increasing rapidly in China. Understanding the contribution of modifiable lifestyle factors on T2DM risk is imperative to prevent the development of T2DM in China. METHODS: We examined associations between lifestyle factors including physical activity, smoking and alcohol consumption with incidence of T2DM among middle-aged and elderly men in urban Shanghai. Information on socio-demographics, lifestyle habits, dietary habits, and disease history was collected via in-person interviews. Anthropometric measurements were taken. A total of 51 464 Chinese men aged 40-74 years free of T2DM, coronary heart disease (CHD), and stroke at baseline were included in the current study. Incident T2DM was identified through follow-up surveys conducted every 2-3 years. Cox proportional hazard analyses were conducted to evaluate associations between lifestyle risk factors and incidence of T2DM. RESULTS: We documented 1304 new cases of T2DM during 276 929 person-years of follow-up (average: 5.4 years). Physical activity was inversely associated with T2DM risk. Daily living, commuting, and total physical activity METs had inverse negative dose-response relationships with T2DM (P-trend = 0.0033, 0.0022, and <0.0001, respectively). Regular participation in exercise or sports reduced T2DM risk (HR = 0.86, 95%CI: 0.76-0.98). Moderate alcohol intake (1-3 drinks/day) was inversely related to T2DM risk (HR = 0.80, 95%CI: 0.67-0.94). Cigarette smoking, on the other hand, was associated with increased T2DM risk; HRs were 1.25 (95%CI: 1.00 1.56) for smoking more than 20 cigarettes per day and 1.28 (95%CI: 1.04-1.57) for smoking more than 40 pack-years. CONCLUSIONS: Physical activity and moderate alcohol intake are inversely associated with T2DM risk, whereas smoking was positively associated with T2DM risk among middle-age and elderly Chinese men. Preventive measures should be developed to focus on these modifiable lifestyle habits to reduce the upward trend of T2DM. PMID- 24223744 TI - A transcription factor code defines nine sensory interneuron subtypes in the mechanosensory area of the spinal cord. AB - Interneurons in the dorsal spinal cord process and relay innocuous and nociceptive somatosensory information from cutaneous receptors that sense touch, temperature and pain. These neurons display a well-defined organization with respect to their afferent innervation. Nociceptive afferents innervate lamina I and II, while cutaneous mechanosensory afferents primarily innervate sensory interneurons that are located in lamina III-IV. In this study, we outline a combinatorial transcription factor code that defines nine different inhibitory and excitatory interneuron populations in laminae III-IV of the postnatal cord. This transcription factor code reveals a high degree of molecular diversity in the neurons that make up laminae III-IV, and it lays the foundation for systematically analyzing and manipulating these different neuronal populations to assess their function. In addition, we find that many of the transcription factors that are expressed in the dorsal spinal cord at early postnatal times continue to be expressed in the adult, raising questions about their function in mature neurons and opening the door to their genetic manipulation in adult animals. PMID- 24223745 TI - Folate deficiency triggers an oxidative-nitrosative stress-mediated apoptotic cell death and impedes insulin biosynthesis in RINm5F pancreatic islet beta cells: relevant to the pathogenesis of diabetes. AB - It has been postulated that folic acid (folate) deficiency (FD) may be a risk factor for the pathogenesis of a variety of oxidative stress-triggered chronic degenerative diseases including diabetes, however, the direct evidence to lend support to this hypothesis is scanty. For this reason, we set out to study if FD can trigger the apoptotic events in an insulin-producing pancreatic RINm5F islet beta cells. When these cells were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature proceeding through a mitochondria-dependent pathway. In addition to evoke oxidative stress, FD condition could also trigger nitrosative stress through a NF-kappaB-dependent iNOS-mediated overproduction of nitric oxide (NO). The latter compound could then trigger depletion of endoplasmic reticulum (ER) calcium (Ca(2+)) store leading to cytosolic Ca(2+) overload and caused ER stress as evidence by the activation of CHOP expression. Furthermore, FD-induced apoptosis of RINm5F cells was found to be correlated with a time-dependent depletion of intracellular glutathione (GSH) and a severe down-regulation of Bcl 2 expression. Along the same vein, we also demonstrated that FD could severely impede RINm5F cells to synthesize insulin and their abilities to secret insulin in response to glucose stimulation were appreciably hampered. Even more importantly, we found that folate replenishment could not restore the ability of RINm5F cells to resynthesize insulin. Taken together, our data provide strong evidence to support the hypothesis that FD is a legitimate risk factor for the pathogenesis of diabetes. PMID- 24223746 TI - Overweight associated with increased risk of erosive esophagitis in a non-obese Taiwanese population. AB - OBJECTIVE: To investigate the relationship between overweight and erosive esophagitis (EE) in a non-obese Taiwanese population. DESIGN AND METHODS: A total of 7,352 subjects (non-obese, 5,826; obese, 1,526) from a health examination center at National Cheng Kung University Hospital were enrolled. Central obesity was defined by a waist circumference (WC) >= 90 cm in male and 80 cm in female. Overweight was defined as body mass index (BMI) of 24-26.9 kg/m(2), and general obesity as BMI >= 27 kg/m(2). The Los Angeles classification was adopted to determine the presence of EE. RESULTS: There were significant differences in the prevalence of central obesity and different BMI status between subjects with and without EE in total and non-obese population. In total population, multivariate analyses revealed central obesity (OR, 1.17, 95% CI, 1.02-1.34, p = 0.021) and being obese (OR, 1.28, 95% CI, 1.07-1.52, p = 0.007)/overweight (OR, 1.25, 95% CI, 1.08-1.45, p = 0.003) had positive associations with EE in different model, respectively. When considering the joint effect of central obesity and BMI status, overweight (OR, 1.22; 95% CI, 1.04-1.44; p = 0.016) remained as an independent associated factor of EE but central obesity (OR, 1.06; 95% CI, 0.89 1.26; p = 0.549)/being obese (OR, 1.22; 95% CI, 0.98-1.53; p = 0.082) did not. As for non-obese group, separate model showed central obesity (OR, 1.19, 95% CI, 1.00-1.40, p = 0.046) and overweight (OR, 1.24; 95% CI, 1.07-1.44, p = 0.005) was positively associated with EE, respectively. However, being overweight (OR, 1.20; 95% CI, 1.02-1.42, p = 0.030) but not central obesity (OR, 1.08; 95% CI, 0.90 1.31; p = 0.398) was positively related to EE with considering the effect of overweight and central obesity simultaneously. CONCLUSION: Overweight effect on EE was more detrimental than central obesity in non-obese subjects. In addition, male gender, hiatus hernia and alcohol use were also associated with increased risk of EE. PMID- 24223747 TI - Modeling the dynamics of bivalent histone modifications. AB - Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains" in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states. PMID- 24223748 TI - Identification and characterization of the transcriptional regulator ChrB in the chromate resistance determinant of Ochrobactrum tritici 5bvl1. AB - Ochrobactrum tritici 5bvl1 is able to resist to high concentrations of chromate through the expression of an inducible chromate-resistant determinant, found in a mobile element (TnOtChr), which carries the genes, chrB, chrA, chrC and chrF. The regulation of chr operon present in TnOtChr, which is controlled by a transcriptional regulator, ChrB, was characterized in the current work. Fusions of chr promoter, or chr promoter and chrB gene, upstream of a gfp reporter gene, identified the most probable promoter sequence within the tnpR-chrB intergenic region. This region contains an AT-rich imperfect inverted repeat sequence, which overlaps a part of the -10 sequence. The results of the in vitro DNA-binding assays with purified ChrB (His- or no-tagged) showed that the protein binds directly to the chr promoter region. In order to identify the ChrB functional domain for sensing chromate stress and for DNA-binding, site-directed mutagenesis of ChrB was performed. Among several single amino acid mutants, three mutants (R180; R187 and H229) prevented chromate induction without any modification to the protein's stability. Interestingly, two ChrB mutants (R18 and R23) were constitutively active, regardless of chromate stress conditions, indicating that the residues most probably belong to the protein-DNA binding site. As such, the ChrB was classified as a transcriptional regulator that recognizes a specific DNA sequence, regulating the expression of a chromate resistance determinant. PMID- 24223749 TI - Structural and enzymatic characterization of the phosphotriesterase OPHC2 from Pseudomonas pseudoalcaligenes. AB - BACKGROUND: Organophosphates (OPs) are neurotoxic compounds for which current methods of elimination are unsatisfactory; thus bio-remediation is considered as a promising alternative. Here we provide the structural and enzymatic characterization of the recently identified enzyme isolated from Pseudomonas pseudoalcaligenes dubbed OPHC2. OPHC2 belongs to the metallo-beta-lactamase superfamily and exhibits an unusual thermal resistance and some OP degrading abilities. PRINCIPAL FINDINGS: The X-ray structure of OPHC2 has been solved at 2.1 A resolution. The enzyme is roughly globular exhibiting a alphabeta/betaalpha topology typical of the metallo-beta-lactamase superfamily. Several structural determinants, such as an extended dimerization surface and an intramolecular disulfide bridge, common features in thermostable enzymes, are consistent with its high Tm (97.8 degrees C). Additionally, we provide the enzymatic characterization of OPHC2 against a wide range of OPs, esters and lactones. SIGNIFICANCE: OPHC2 possesses a broad substrate activity spectrum, since it hydrolyzes various phosphotriesters, esters, and a lactone. Because of its organophosphorus hydrolase activity, and given its intrinsic thermostability, OPHC2 is an interesting candidate for the development of an OPs bio decontaminant. Its X-ray structure shed light on its active site, and provides key information for the understanding of the substrate binding mode and catalysis. PMID- 24223750 TI - Modeling the structure of RNA molecules with small-angle X-ray scattering data. AB - We propose a novel fragment assembly method for low-resolution modeling of RNA and show how it may be used along with small-angle X-ray solution scattering (SAXS) data to model low-resolution structures of particles having as many as 12 independent secondary structure elements. We assessed this model-building procedure by using both artificial data on a previously proposed benchmark and publicly available data. With the artificial data, SAXS-guided models show better similarity to native structures than ROSETTA decoys. The publicly available data showed that SAXS-guided models can be used to reinterpret RNA structures previously deposited in the Protein Data Bank. Our approach allows for fast and efficient building of de novo models of RNA using approximate secondary structures that can be readily obtained from existing bioinformatic approaches. We also offer a rigorous assessment of the resolving power of SAXS in the case of small RNA structures, along with a small multimetric benchmark of the proposed method. PMID- 24223751 TI - Frequency response and gap tuning for nonlinear electrical oscillator networks. AB - We study nonlinear electrical oscillator networks, the smallest example of which consists of a voltage-dependent capacitor, an inductor, and a resistor driven by a pure tone source. By allowing the network topology to be that of any connected graph, such circuits generalize spatially discrete nonlinear transmission lines/lattices that have proven useful in high-frequency analog devices. For such networks, we develop two algorithms to compute the steady-state response when a subset of nodes are driven at the same fixed frequency. The algorithms we devise are orders of magnitude more accurate and efficient than stepping towards the steady-state using a standard numerical integrator. We seek to enhance a given network's nonlinear behavior by altering the eigenvalues of the graph Laplacian, i.e., the resonances of the linearized system. We develop a Newton-type method that solves for the network inductances such that the graph Laplacian achieves a desired set of eigenvalues; this method enables one to move the eigenvalues while keeping the network topology fixed. Running numerical experiments using three different random graph models, we show that shrinking the gap between the graph Laplacian's first two eigenvalues dramatically improves a network's ability to (i) transfer energy to higher harmonics, and (ii) generate large-amplitude signals. Our results shed light on the relationship between a network's structure, encoded by the graph Laplacian, and its function, defined in this case by the presence of strongly nonlinear effects in the frequency response. PMID- 24223752 TI - Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. AB - BACKGROUND: There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined. METHODS: We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. RESULTS: We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. CONCLUSION: This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer. PMID- 24223753 TI - MicroRNA-4723 inhibits prostate cancer growth through inactivation of the Abelson family of nonreceptor protein tyrosine kinases. AB - The Abelson (c-Abl) proto-oncogene encodes a highly conserved nonreceptor protein tyrosine kinase that plays a role in cell proliferation, differentiation, apoptosis and cell adhesion. c-Abl represents a specific anti-cancer target in prostate cancer as aberrant activity of this kinase has been implicated in the stimulation of prostate cancer growth and progression. However, the mechanism of regulation of c-Abl is not known. Here we report that Abl kinases are regulated by a novel microRNA, miR-4723, in prostate cancer. Expression profiling of miR 4723 expression in a cohort of prostate cancer clinical specimens showed that miR 4723 expression is widely attenuated in prostate cancer. Low miR-4723 expression was significantly correlated with poor survival outcome and our analyses suggest that miR-4723 has significant potential as a disease biomarker for diagnosis and prognosis in prostate cancer. To evaluate the functional significance of decreased miR-4723 expression in prostate cancer, miR-4723 was overexpressed in prostate cancer cell lines followed by functional assays. miR-4723 overexpression led to significant decreases in cell growth, clonability, invasion and migration. Importantly, miR-4723 expression led to dramatic induction of apoptosis in prostate cancer cell lines suggesting that miR-4723 is a pro-apoptotic miRNA regulating prostate carcinogenesis. Analysis of putative miR-4723 targets showed that miR-4723 targets integrin alpha 3 and Methyl CpG binding protein in addition to Abl1 and Abl2 kinases. Further, we found that the expression of Abl kinase is inversely correlated with miR-4723 expression in prostate cancer clinical specimens. Also, Abl1 knockdown partially phenocopies miR-4723 reexpression in prostate cancer cells suggesting that Abl is a functionally relevant target of miR-4723 in prostate cancer. In conclusion, we have identified a novel microRNA that mediates regulation of Abl kinases in prostate cancer. This study suggests that miR-4723 may be an attractive target for therapeutic intervention in prostate cancer. PMID- 24223754 TI - Repression of tropolone production and induction of a Burkholderia plantarii pseudo-biofilm by carot-4-en-9,10-diol, a cell-to-cell signaling disrupter produced by Trichoderma virens. AB - BACKGROUND: The tropolone-tolerant Trichoderma virens PS1-7 is a biocontrol agent against Burkholderia plantarii, causative of rice seedling blight. When exposed to catechol, this fungus dose-dependently produced carot-4-en-9,10-diol, a sesquiterpene-type autoregulatory signal molecule that promotes self-conidiation of T. virens PS1-7 mycelia. It was, however, uncertain why T. virens PS1-7 attenuates the symptom development of the rice seedlings infested with B. plantarii. METHODOLOGY/PRINCIPAL FINDINGS: To reveal the antagonism by T. virens PS1-7 against B. plantarii leading to repression of tropolone production in a coculture system, bioassay-guided screening for active compounds from a 3-d culture of T. virens PS1-7 was conducted. As a result, carot-4-en-9,10-diol was identified and found to repress tropolone production of B. plantarii from 10 to 200 uM in a dose-dependent manner as well as attenuate virulence of B. plantarii on rice seedlings. Quantitative RT-PCR analysis revealed that transcriptional suppression of N-acyl-L-homoserine lactone synthase plaI in B. plantarii was the main mode of action by which carot-4-en-9,10-diol mediated the quorum quenching responsible for repression of tropolone production. In addition, the unique response of B. plantarii to carot-4-en-9,10-diol in the biofilm formed in the static culture system was also found. Although the initial stage of B. plantarii biofilm formation was induced by both tropolone and carot-4-en-9,10-diol, it was induced in different states. Moreover, the B. plantarii biofilm that was induced by carot-4-en-9,10-diol at the late stage showed defects not only in matrix structure but also cell viability. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that carot-4-en-9,10-diol released by T. virens PS1-7 acts as an interkingdom cell-to-cell signaling molecule against B. plantarii to repress tropolone production and induces pseudo-biofilm to the cells. This observation also led to another discovery that tropolone is an autoregulatory cell-to-cell signaling molecule of B. plantarii that induces a functional biofilm other than a simple B. plantarii virulence factor. PMID- 24223755 TI - Comprehensive analysis of single nucleotide polymorphisms in human microRNAs. AB - MicroRNAs (miRNAs) are endogenous small non-coding RNAs that repress their targets at post transcriptional level. Single Nucleotide Polymorphisms (SNPs) in miRNAs can lead to severe defects to the functions of miRNAs and might result in diseases. Although several studies have tried to identify the SNPs in human miRNA genes or only in the mature miRNAs, there are only limited endeavors to explain the distribution of SNPs in these important genes. After a genome-wide scan for SNPs in human miRNAs, we totally identified 1899 SNPs in 961 out of the 1527 reported miRNA precursors of human, which is the most complete list of SNPs in human miRNAs to date. More importantly, to explain the distributions of SNPs existed in human miRNAs, we comprehensively and systematically analyzed the identified SNPs in miRNAs from several aspects. Our results suggest that conservation, genomic context, secondary structure, and functional importance of human miRNAs affect the accumulations of SNPs in these genes. Our results also show that the number of SNPs with significantly different frequencies among various populations in the HapMap and 1000 Genome Project data are consistent with the geographical distributions of these populations. These analyses provide a better insight of SNPs in human miRNAs and the spreading of the SNPs in miRNAs in different populations. PMID- 24223756 TI - Causes, coping, and culture: a comparative survey study on representation of back pain in three Swiss language regions. AB - INTRODUCTION: This study intends to contribute to a research tradition that asks how causal attributions of illnesses affect coping behavior. Causal attributions are understood as the most important element of illness representations and coping as a means to preserve quality of life. The issue is applied to a condition so far often neglected in research on illness representations-back pain and a third concept is added to the picture: culture. AIM: The aim of this study is (a) to explore the causal factors to which persons with back pain attribute the further course of their illness, (b) to find out whether the attributed causes are predictors of coping maxims, and (c) to find out whether cultural factors affect attributions and coping and moderate the relationship between the two. METHODS: A total of 1259 gainfully employed or self-employed persons with recent episodes of back pain were recruited in the three language regions of Switzerland. They were asked to complete a structured online interview, measuring among many other variables attributed causes, coping maxims, and affiliation to one of the Swiss micro-cultures (German-, French- or Italian-speaking). RESULTS: Attributed causes of the illness that can be influenced by a patient go along with more active coping styles. Cultural affiliation impacts on coping maxims independently, but culture moderates the relationship of attributed causes and coping maxims only in two of twenty possible cases. IMPLICATIONS: The results show that cultural differences can be analytically incorporated in the models of illness representations. Results may help to improve healthcare providers' communication with patients and plan public health campaigns. The approach to micro-cultural differences and the substantive relationships between alterability of causes and activity in coping may help the further development of models of illness representations. PMID- 24223757 TI - FLZ alleviates the memory deficits in transgenic mouse model of Alzheimer's disease via decreasing beta-amyloid production and tau hyperphosphorylation. AB - Alzheimer's disease (AD) is the most common cause of dementia worldwide and mainly characterized by the aggregated beta-amyloid (Abeta) and hyperphosphorylated tau. FLZ is a novel synthetic derivative of natural squamosamide and has been proved to improve memory deficits in dementia animal models. In this study, we aimed to investigate the mechanisms of FLZ's neuroprotective effect in APP/PS1 double transgenic mice and SH-SY5Y (APPwt/swe) cells. The results showed that treatment with FLZ significantly improved the memory deficits of APP/PS1 transgenic mice and decreased apoptosis of SH-SY5Y (APPwt/swe) cells. FLZ markedly attenuated Abeta accumulation and tau phosphorylation both in vivo and in vitro. Mechanistic study showed that FLZ interfered APP processing, i.e., FLZ decreased beta-amyloid precursor protein (APP) phosphorylation, APP-carboxy-terminal fragment (APP-CTF) production and beta-amyloid precursor protein cleaving enzyme 1 (BACE1) expression. These results indicated that FLZ reduced Abeta production through inhibiting amyloidogenic pathway. The mechanistic study about FLZ's inhibitory effect on tau phosphorylation revealed t the involvement of Akt/glycogen synthase kinase 3beta (GSK3beta) pathway. FLZ treatment increased Akt activity and inhibited GSK3beta activity both in vivo and in vitro. The inhibitory effect of FLZ on GSK3beta activity and tau phosphorylation was suppressed by inhibiting Akt activity, indicating that Akt/GSK3beta pathway might be the possible mechanism involved in the inhibitory effect of FLZ on tau hyperphosphorylation. These results suggested FLZ might be a potential anti-AD drug as it not only reduced Abeta production via inhibition amyloidogenic APP processing pathway, but also attenuated tau hyperphosphoylation mediated by Akt/GSK3beta. PMID- 24223758 TI - Genome-wide association mapping of root traits in a japonica rice panel. AB - Rice is a crop prone to drought stress in upland and rainfed lowland ecosystems. A deep root system is recognized as the best drought avoidance mechanism. Genome wide association mapping offers higher resolution for locating quantitative trait loci (QTLs) than QTL mapping in biparental populations. We performed an association mapping study for root traits using a panel of 167 japonica accessions, mostly of tropical origin. The panel was genotyped at an average density of one marker per 22.5 kb using genotyping by sequencing technology. The linkage disequilibrium in the panel was high (r(2)>0.6, on average, for 20 kb mean distances between markers). The plants were grown in transparent 50 cm * 20 cm * 2 cm Plexiglas nailboard sandwiches filled with 1.5 mm glass beads through which a nutrient solution was circulated. Root system architecture and biomass traits were measured in 30-day-old plants. The panel showed a moderate to high diversity in the various traits, particularly for deep (below 30 cm depth) root mass and the number of deep roots. Association analyses were conducted using a mixed model involving both population structure and kinship to control for false positives. Nineteen associations were significant at P<1e-05, and 78 were significant at P<1e-04. The greatest numbers of significant associations were detected for deep root mass and the number of deep roots, whereas no significant associations were found for total root biomass or deep root proportion. Because several QTLs for different traits were co-localized, 51 unique loci were detected; several co-localized with meta-QTLs for root traits, but none co localized with rice genes known to be involved in root growth. Several likely candidate genes were found in close proximity to these loci. Additional work is necessary to assess whether these markers are relevant in other backgrounds and whether the genes identified are robust candidates. PMID- 24223759 TI - Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer. AB - BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution. METHODS: Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-gamma levels after stimulation of the peripheral blood with Promoca(r). To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16(+)CD56(dim) and CD16(-)CD56(bright) cells gated on CD56(+)CD3(-) cells were analyzed using a flow cytometer. RESULTS: NKA and the proportion of CD56(bright) cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56(dim)-to-CD56(bright) cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56(bright) cells in relation to the alteration of CD56(dim) cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786). CONCLUSIONS: Reduction of CD56(bright) cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies. PMID- 24223760 TI - Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV core DII protein. AB - Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein's lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV. PMID- 24223761 TI - Prognostic significance of circulating tumor cells in non-small-cell lung cancer patients: a meta-analysis. AB - BACKGROUND: The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta analysis. METHODS: We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.59-1.33; Z = 0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18-3.62; Z = 2.20; P = 0.027) and tumor stage (OR = 1.95; 95% CI: 1.08-3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR] = 2.19; 95% CI: 1.53-3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR = 2.14; 95% CI: 1.36-3.38; Z = 3.28; P<0.0001). CONCLUSION: The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well designed prospective studies are required to explore the clinical applications of CTCs in lung cancer. PMID- 24223762 TI - Making research data repositories visible: the re3data.org Registry. AB - Researchers require infrastructures that ensure a maximum of accessibility, stability and reliability to facilitate working with and sharing of research data. Such infrastructures are being increasingly summarized under the term Research Data Repositories (RDR). The project re3data.org-Registry of Research Data Repositories-has begun to index research data repositories in 2012 and offers researchers, funding organizations, libraries and publishers an overview of the heterogeneous research data repository landscape. In July 2013 re3data.org lists 400 research data repositories and counting. 288 of these are described in detail using the re3data.org vocabulary. Information icons help researchers to easily identify an adequate repository for the storage and reuse of their data. This article describes the heterogeneous RDR landscape and presents a typology of institutional, disciplinary, multidisciplinary and project-specific RDR. Further the article outlines the features of re3data.org, and shows how this registry helps to identify appropriate repositories for storage and search of research data. PMID- 24223763 TI - Expression of NgBR is highly associated with estrogen receptor alpha and survivin in breast cancer. AB - NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF 7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction in breast cancer. PMID- 24223764 TI - Th17/IL-17A might play a protective role in chronic lymphocytic leukemia immunity. AB - Th17 cells, a recently discovered subset of T helper cells that secrete IL-17A, can affect the inflammation process autoimmune and cancer diseases development. The purpose of this study was to evaluate the role of Th17 cells and IL17A in biology of CLL. The study group included 294 untreated CLL patients in different clinical stages. Here, we show that higher Th17 and IL-17A values were associated with less advanced clinical stage of CLL. Th17 cells' percentages in PB were lower in patients who died due to CLL during follow-up due to CLL (as compared to surviving patients) and in patients responding to first-line therapy with fludarabine-based regimens (as compared to non-responders). IL-17A inversely correlated with the time from CLL diagnosis to the start of therapy and was lower in patients who required treatment during follow-up. Th-17 and IL-17A values were lower in patients with adverse prognostic factors (17p and 11q deletion, CD38 and ZAP-70 expression). CLL patients with detectable IL-17A mRNA in T cells were in Rai Stage 0 and negative for both ZAP-70 and CD38 expression. Th17 percentages positively correlated with iNKT and adversely with Treg cells. The results of this study suggest that Th17 may play a beneficial role in CLL immunity. PMID- 24223765 TI - Functional characterization of a wheat NHX antiporter gene TaNHX2 that encodes a K(+)/H(+) exchanger. AB - The subcellular localization of a wheat NHX antiporter, TaNHX2, was studied in Arabidopsis protoplasts, and its function was evaluated using Saccharomyces cerevisiae as a heterologous expression system. Fluorescence patterns of TaNHX2 GFP fusion protein in Arabidopsis cells indicated that TaNHX2 localized at endomembranes. TaNHX2 has significant sequence homology to NHX sodium exchangers from Arabidopsis, is abundant in roots and leaves and is induced by salt or dehydration treatments. Western blot analysis showed that TaNHX2 could be expressed in transgenic yeast cells. Expressed TaNHX2 protein suppressed the salt sensitivity of a yeast mutant strain by increasing its K(+) content when exposed to salt stress. TaNHX2 also increased the tolerance of the strain to potassium stress. However, the expression of TaNHX2 did not affect the sodium concentration in transgenic cells. Western blot analysis for tonoplast proteins indicated that the TaNHX2 protein localized at the tonoplast of transgenic yeast cells. The tonoplast vesicles from transgenic yeast cells displayed enhanced K(+)/H(+) exchange activity but very little Na(+/)H(+) exchange compared with controls transformed with the empty vector; Na(+)/H(+) exchange was not detected with concentrations of less than 37.5 mM Na(+) in the reaction medium. Our data suggest that TaNHX2 is a endomembrane-bound protein and may primarily function as a K(+)/H(+) antiporter, which is involved in cellular pH regulation and potassium nutrition under normal conditions. Under saline conditions, the protein mediates resistance to salt stress through the intracellular compartmentalization of potassium to regulate cellular pH and K(+) homeostasis. PMID- 24223766 TI - Mapping the shapes of phylogenetic trees from human and zoonotic RNA viruses. AB - A phylogeny is a tree-based model of common ancestry that is an indispensable tool for studying biological variation. Phylogenies play a special role in the study of rapidly evolving populations such as viruses, where the proliferation of lineages is constantly being shaped by the mode of virus transmission, by adaptation to immune systems, and by patterns of human migration and contact. These processes may leave an imprint on the shapes of virus phylogenies that can be extracted for comparative study; however, tree shapes are intrinsically difficult to quantify. Here we present a comprehensive study of phylogenies reconstructed from 38 different RNA viruses from 12 taxonomic families that are associated with human pathologies. To accomplish this, we have developed a new procedure for studying phylogenetic tree shapes based on the 'kernel trick', a technique that maps complex objects into a statistically convenient space. We show that our kernel method outperforms nine different tree balance statistics at correctly classifying phylogenies that were simulated under different evolutionary scenarios. Using the kernel method, we observe patterns in the distribution of RNA virus phylogenies in this space that reflect modes of transmission and pathogenesis. For example, viruses that can establish persistent chronic infections (such as HIV and hepatitis C virus) form a distinct cluster. Although the visibly 'star-like' shape characteristic of trees from these viruses has been well-documented, we show that established methods for quantifying tree shape fail to distinguish these trees from those of other viruses. The kernel approach presented here potentially represents an important new tool for characterizing the evolution and epidemiology of RNA viruses. PMID- 24223767 TI - Zn subcellular distribution in liver of goldfish (carassius auratus) with exposure to zinc oxide nanoparticles and mechanism of hepatic detoxification. AB - Zinc Oxide Nanoparticles (ZnO NPs) have attracted increasing concerns because of their widespread use and toxic potential. In this study, Zn accumulations in different tissues (gills, liver, muscle, and gut) of goldfish (Carassius auratus) after exposure to ZnO NPs were studied in comparison with bulk ZnO and Zn(2+). And the technique of subcellular partitioning was firstly used on the liver of goldfish to study the hepatic accumulation of ZnO NPs. The results showed that at sublethal Zn concentration (2 mg/L), bioaccumulation in goldfish was tissue specific and dependent on the exposure materials. Compared with Zn(2+), the particles of bulk ZnO and the ZnO NPs appeared to aggregate in the environmentally contacted tissues (gills and gut), rather than transport to the internal tissues (liver and muscle). The subcellular distributions of liver differed for the three exposure treatments. After ZnO NPs exposure, Zn percentage in metal-rich granule (MRG) increased significantly, and after Zn(2+) exposure, it increased significantly in the organelles. Metallothionein-like proteins (MTLP) were the main target for Zn(2+), while MRG played dominant role for ZnO NPs. The different results of subcellular distributions revealed that metal detoxification mechanisms of liver for ZnO NPs, bulk ZnO, and Zn(2+) were different. Overall, subcellular partitioning provided an interesting start to better understanding of the toxicity of nano- and conventional materials. PMID- 24223768 TI - Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis. AB - Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and -negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV- HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV- HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV- tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV- HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV- HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers. PMID- 24223769 TI - Non-invasive prenatal testing of trisomy 18 by an epigenetic marker in first trimester maternal plasma. AB - BACKGROUND: Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell free total DNA marker in the first trimester of pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%. CONCLUSIONS: Our results suggest that U-maspin and M maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus. PMID- 24223770 TI - UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila. AB - In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA), orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79) and unc80 (aka CG18437). We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior. PMID- 24223771 TI - New insights into the RNA-based mechanism of action of the anticancer drug 5' fluorouracil in eukaryotic cells. AB - 5-Fluorouracil (5FU) is a chemotherapeutic drug widely used in treating a range of advanced, solid tumours and, in particular, colorectal cancer. Here, we used high-density tiling DNA microarray technology to obtain the specific transcriptome-wide response induced by 5FU in the eukaryotic model Schizosaccharomyces pombe. This approach combined with real-time quantitative PCR analysis allowed us to detect splicing defects of a significant number of intron containing mRNA, in addition to identify some rRNA and tRNA processing defects after 5FU treatment. Interestingly, our studies also revealed that 5FU specifically induced the expression of certain genes implicated in the processing of mRNA, tRNA and rRNA precursors, and in the post-transcriptional modification of uracil residues in RNA. The transcription of several tRNA genes was also significantly induced after drug exposure. These transcriptional changes might represent a cellular response mechanism to counteract 5FU damage since deletion strains for some of these up-regulated genes were hypersensitive to 5FU. Moreover, most of these RNA processing genes have human orthologs that participate in conserved pathways, suggesting that they could be novel targets to improve the efficacy of 5FU-based treatments. PMID- 24223772 TI - Vascular endothelial growth factor +936C/T, -634G/C, -2578C/A, and -1154G/A polymorphisms with risk of preeclampsia: a meta-analysis. AB - BACKGROUND: Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual's susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08-2.12) or -634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03-1.50) was associated with the risk of PE, whereas there was no association between -2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82-1.16) or 1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94-1.78) polymorphism and PE risk in our study. CONCLUSION: Our meta-analysis suggested that VEGF -2578C/A or -1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or -634G/C polymorphism and risk of PE. PMID- 24223773 TI - High-resolution structural and functional assessments of cerebral microvasculature using 3D Gas DeltaR2*-mMRA. AB - The ability to evaluate the cerebral microvascular structure and function is crucial for investigating pathological processes in brain disorders. Previous angiographic methods based on blood oxygen level-dependent (BOLD) contrast offer appropriate visualization of the cerebral vasculature, but these methods remain to be optimized in order to extract more comprehensive information. This study aimed to integrate the advantages of BOLD MRI in both structural and functional vascular assessments. The BOLD contrast was manipulated by a carbogen challenge, and signal changes in gradient-echo images were computed to generate DeltaR2* maps. Simultaneously, a functional index representing the regional cerebral blood volume was derived by normalizing the DeltaR2* values of a given region to those of vein-filled voxels of the sinus. This method is named 3D gas DeltaR2*-mMRA (microscopic MRA). The advantages of using 3D gas DeltaR2*-mMRA to observe the microvasculature include the ability to distinguish air-tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood-brain barrier. A stroke model was used to demonstrate the ability of 3D gas DeltaR2* mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as magnifying vessel sizes and predominantly revealing venous vessels. PMID- 24223774 TI - GPS2 is required for the association of NS5A with VAP-A and hepatitis C virus replication. AB - Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a component of the replication complex associated with various cellular proteins. It has been reported that G protein pathway suppressor 2 (GPS2) is a potential NS5A-binding factor, as identified in a yeast two-hybrid screens of human cDNA library using viral proteins as baits [1]. In this study, we demonstrated the interaction between GPS2 and NS5A in mammalian cells by coimmunoprecipitation analysis and found that both exogenously and endogenously expressed GPS2 interacted with NS5A of genotype 1b and 2a. Mutagenesis study demonstrated that Domain I of NS5A and coiled-coil domain of GPS2 are responsible for the interaction. Knockdown of GPS2 in hepatoma cell lines suppressed the replication of HCV RNA, which can be rescued by the expression of an RNAi-resistant GPS2. Furthermore, overexpression of GPS2 enhanced the association of NS5A with a proviral cellular factor, human vesicle-associated membrane protein-associated protein A (VAP-A), while knockdown of GPS2 disrupted interaction between VAP-A and NS5A. Taken together, our results suggest that GPS2 acts as a bridge between NS5A and VAP-A and is required for efficient HCV replication. PMID- 24223775 TI - Cross-sectional study on attitudes among general practitioners towards pneumococcal vaccination for middle-aged and elderly population in Hong Kong. AB - OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64) and elderly population (over 65) in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%). Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1), and attending 6 pneumonia cases or more per year (ORm 2.28) were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41), consultation not related to vaccination (ORm 0.45) and limited time (ORm 0.38) were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures. PMID- 24223776 TI - External validation of the derived neutrophil to lymphocyte ratio as a prognostic marker on a large cohort of pancreatic cancer patients. AB - BACKGROUND: With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients. METHODS: Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied. RESULTS: We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients' survival in the whole cohort. Kaplan-Meier curve reveals a dNLR>=2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR>=2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01-1.51, p = 0.041) was identified. CONCLUSION: In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability. PMID- 24223777 TI - Anaerobic co-culture of mesenchymal stem cells and anaerobic pathogens - a new in vitro model system. AB - BACKGROUND: Human mesenchymal stem cells (hMSCs) are multipotent by nature and are originally isolated from bone marrow. In light of a future application of hMSCs in the oral cavity, a body compartment with varying oxygen partial pressures and an omnipresence of different bacterial species i.e. periodontitis pathogens, we performed this study to gain information about the behavior of hMSC in an anaerobic system and the response in interaction with oral bacterial pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We established a model system with oral pathogenic bacterial species and eukaryotic cells cultured in anaerobic conditions. The facultative anaerobe bacteria Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied. Their effects on hMSCs and primary as well as permanent gingival epithelial cells (Ca9-22, HGPEC) were comparatively analyzed. We show that hMSCs cope with anoxic conditions, since 40% vital cells remain after 72 h of anaerobic culture. The Ca9 22 and HGPEC cells are significantly more sensitive to lack of oxygen. All bacterial species reveal a comparatively low adherence to and internalization into hMSCs (0.2% and 0.01% of the initial inoculum, respectively). In comparison, the Ca9-22 and HGPEC cells present better targets for bacterial adherence and internalization. The production of the pro-inflammatory chemokine IL-8 is higher in both gingival epithelial cell lines compared to hMSCs and Fusobacterium nucleatum induce a time-dependent cytokine secretion in both cell lines. Porphyromonas gingivalis is less effective in stimulating secretion of IL-8 in the co-cultivation experiments. CONCLUSIONS/SIGNIFICANCE: HMSCs are suitable for use in anoxic regions of the oral cavity. The interaction with local pathogenic bacteria does not result in massive pro-inflammatory cytokine responses. The test system established in this study allowed further investigation of parameters prior to set up of oral hMSC in vivo studies. PMID- 24223778 TI - Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury. AB - A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-gamma-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01), promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05), reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx 1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05), and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0.01). Therefore, hucMSC-Trx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI. PMID- 24223780 TI - Three-dimensional flow of an oldroyd-B fluid with variable thermal conductivity and heat generation/absorption. AB - This paper looks at the series solutions of three dimensional boundary layer flow. An Oldroyd-B fluid with variable thermal conductivity is considered. The flow is induced due to stretching of a surface. Analysis has been carried out in the presence of heat generation/absorption. Homotopy analysis is implemented in developing the series solutions to the governing flow and energy equations. Graphs are presented and discussed for various parameters of interest. Comparison of present study with the existing limiting solution is shown and examined. PMID- 24223779 TI - Protein N-myristoylation plays a critical role in the endoplasmic reticulum morphological change induced by overexpression of protein Lunapark, an integral membrane protein of the endoplasmic reticulum. AB - N-myristoylation of eukaryotic cellular proteins has been recognized as a modification that occurs mainly on cytoplasmic proteins. In this study, we examined the membrane localization, membrane integration, and intracellular localization of four recently identified human N-myristoylated proteins with predicted transmembrane domains. As a result, it was found that protein Lunapark, the human ortholog of yeast protein Lnp1p that has recently been found to be involved in network formation of the endoplasmic reticulum (ER), is an N myristoylated polytopic integral membrane protein. Analysis of tumor necrosis factor-fusion proteins with each of the two putative transmembrane domains and their flanking regions of protein Lunapark revealed that transmembrane domain 1 and 2 functioned as type II signal anchor sequence and stop transfer sequence, respectively, and together generated a double-spanning integral membrane protein with an N-/C-terminal cytoplasmic orientation. Immunofluorescence staining of HEK293T cells transfected with a cDNA encoding protein Lunapark tagged with FLAG tag at its C-terminus revealed that overexpressed protein Lunapark localized mainly to the peripheral ER and induced the formation of large polygonal tubular structures. Morphological changes in the ER induced by overexpressed protein Lunapark were significantly inhibited by the inhibition of protein N myristoylation by means of replacing Gly2 with Ala. These results indicated that protein N-myristoylation plays a critical role in the ER morphological change induced by overexpression of protein Lunapark. PMID- 24223782 TI - A mechanistic individual-based model of the feeding processes for Oikopleura dioica. AB - A mechanistic physiological model of the appendicularian Oikopleura dioica has been built to represent its three feeding processes (filtration, ingestion and assimilation). The mathematical formulation of these processes is based on laboratory observations from the literature, and tests different hypotheses. This model accounts for house formation dynamics, the food storage capacity of the house and the gut throughput dynamics. The half-saturation coefficient for ingestion resulting from model simulations is approximately 28 [Formula: see text] and is independent of the weight of the organism. The maximum food intake for ingestion is also a property of the model and depends on the weight of the organism. Both are in accordance with data from the literature. The model also provides a realistic representation of carbon accumulation within the house. The modelled half-saturation coefficient for assimilation is approximately 15 [Formula: see text] and is also independent of the weight of the organism. Modelled gut throughput dynamics are based on faecal pellet formation by gut compaction. Model outputs showed that below a food concentration of 30 [Formula: see text], the faecal pellet weight should represent a lower proportion of the body weight of the organism, meaning that the faecal pellet formation is not driven by gut filling. Simulations using fluctuating environmental food availability show that food depletion is not immediately experienced by the organism but that it occurs after a lag time because of house and gut buffering abilities. This lag time duration lasts at least 30 minutes and can reach more than 2 hours, depending on when the food depletion occurs during the house lifespan. PMID- 24223781 TI - RTK/ERK pathway under natural selection associated with prostate cancer. AB - Prostate cancer (PCa) is a global disease causing large numbers of deaths every year. Recent studies have indicated the RTK/ERK pathway might be a key pathway in the development of PCa. However, the exact association and evolution-based mechanism remain unclear. This study was conducted by combining genotypic and phenotypic data from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) with related databases such as the HapMap Project and Genevar. In this analysis, expression of quantitative trait loci (eQTLs) analysis, natural selection and gene-based pathway analysis were involved. The pathway analysis confirmed the positive relationship between PCa risk and several key genes. In addition, combined with the natural selection, it seems that 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) especially rs17172432, might be pivotal factors in the development of PCa. The results indicate that the RTK/ERK pathway under natural selection is a key link in PCa risk. The joint effect of the genes and loci with positive selection might be one reason for the development of PCa. Dealing with all the factors simultaneously might give insight into prevention and aid in predicting the success of potential therapies for PCa. PMID- 24223783 TI - Initial d2 dopamine receptor sensitivity predicts cocaine sensitivity and reward in rats. AB - The activation of dopamine receptors within the mesolimbic dopamine system is known to be involved in the initiation and maintenance of cocaine use. Expression of the D2 dopamine receptor subtype has been implicated as both a predisposing factor and consequence of chronic cocaine use. It is unclear whether there is a predictive relationship between D2 dopamine receptor function and cocaine sensitivity that would enable cocaine abuse. Therefore, we exploited individual differences in behavioral responses to D2 dopamine receptor stimulation to test its relationship with cocaine-mediated behaviors. Outbred, male Sprague-Dawley rats were initially characterized by their locomotor responsiveness to the D2 dopamine receptor agonist, quinpirole, in a within-session ascending dose response regimen (0, 0.1, 0.3 & 1.0 mg/kg, sc). Rats were classified as high or low quinpirole responders (HD2 and LD2, respectively) by a median split of their quinpirole-induced locomotor activity. Rats were subsequently tested for differences in the psychostimulant effects of cocaine by measuring changes in cocaine-induced locomotor activity (5 and 15 mg/kg, ip). Rats were also tested for differences in the development of conditioned place preference to a low dose of cocaine (7.5 mg/kg, ip) that does not reliably produce a cocaine conditioned place preference. Finally, rats were tested for acquisition of cocaine self administration and maintenance responding on fixed ratio 1 and 5 schedules of reinforcement, respectively. Results demonstrate that HD2 rats have enhanced sensitivity to the locomotor stimulating properties of cocaine, display greater cocaine conditioned place preference, and self-administer more cocaine compared to LD2 animals. These findings suggest that individual differences in D2 dopamine receptor sensitivity may be predictive of cocaine sensitivity and reward. PMID- 24223784 TI - Develop to term rat oocytes injected with heat-dried sperm heads. AB - This study investigated the development of rat oocytes in vitro and in vivo following intracytoplasmic injection of heads from spermatozoa heat-dried at 50 degrees C for 8 h and stored at 4 degrees C in different gas phases. Sperm membrane and chromosome are damaged by the process of heat-drying. Oocyte activation and cleavage of oocytes were worse in oocytes injected with spermatozoa heat-dried and stored for 1 week than unheated, fresh spermatozoa, but in heat-dried spermatozoa, there were no differences in these abilities of oocytes between the samples stored in nitrogen gas and in air. The oocytes injected with heat-dried spermatozoa stored for 1 week could develop to the morula and blastocyst stages without difference between the samples stored in nitrogen gas and in air after artificial stimulation. Cleavage of oocytes and development of cleaved embryos were higher when heat-dried spermatozoa were stored for 3 and 6 months in nitrogen gas than in air. However, the ability of injected oocytes to develop to the morula and blastocyst stages was not inhibited even when heat-dried spermatozoa stored in both atmosphere conditions for as long as 6 months were used. When 2-cell embryos derived from oocytes injected with heads from spermatozoa heat-dried and stored for 1 week and 1 month were transferred, each 1 of 4 recipients was conceived, and the conceived recipients delivered 1 live young each. These results demonstrate that rat oocytes can be fertilized with heat-dried spermatozoa and that the fertilized oocytes can develop to term. PMID- 24223785 TI - Complex processing patterns of mRNAs of the large ATP synthase operon in Arabidopsis chloroplasts. AB - Chloroplasts are photosynthetic cell organelles which have evolved from endosymbiosis of the cyanobacterial ancestor. In chloroplasts, genes are still organized into transcriptional units as in bacteria but the corresponding poly cistronic mRNAs undergo complex processing events, including inter-genic cleavage and 5' and 3' end-definition. The current model for processing proposes that the 3' end of the upstream cistron transcripts and the 5' end of the downstream cistron transcripts are defined by the same RNA-binding protein and overlap at the level of the protein-binding site. We have investigated the processing mechanisms that operate within the large ATP synthase (atp) operon, in Arabidopsis thaliana chloroplasts. This operon is transcribed by the plastid encoded RNA polymerase starting from two promoters, which are upstream and within the operon, respectively, and harbors four potential sites for RNA-binding proteins. In order to study the functional significance of the promoters and the protein-binding sites for the maturation processes, we have performed a detailed mapping of the atp transcript ends. Our data indicate that in contrast to maize, atpI and atpH transcripts with overlapping ends are very rare in Arabidopsis. In addition, atpA mRNAs, which overlap with atpF mRNAs, are even truncated at the 3' end, thus representing degradation products. We observe, instead, that the 5' ends of nascent poly-cistronic atp transcripts are defined at the first protein binding site which follows either one of the two transcription initiation sites, while the 3' ends are defined at the subsequent protein-binding sites or at hairpin structures that are encountered by the progressing RNA polymerase. We conclude that the overlapping mechanisms of mRNA protection have only a limited role in obtaining stable processed atp mRNAs in Arabidopsis. Our findings suggest that during evolution of different plant species as maize and Arabidopsis, chloroplasts have evolved multiple strategies to produce mature transcripts suitable for translation. PMID- 24223786 TI - Increase in cellulose accumulation and improvement of saccharification by overexpression of arabinofuranosidase in rice. AB - Cellulosic biomass is available for the production of biofuel, with saccharification of the cell wall being a key process. We investigated whether alteration of arabinoxylan, a major hemicellulose in monocots, causes an increase in saccharification efficiency. Arabinoxylans have beta-1,4-D-xylopyranosyl backbones and 1,3- or 1,4-alpha-l-arabinofuranosyl residues linked to O-2 and/or O-3 of xylopyranosyl residues as side chains. Arabinose side chains interrupt the hydrogen bond between arabinoxylan and cellulose and carry an ester-linked feruloyl substituent. Arabinose side chains are the base point for diferuloyl cross-links and lignification. We analyzed rice plants overexpressing arabinofuranosidase (ARAF) to study the role of arabinose residues in the cell wall and their effects on saccharification. Arabinose content in the cell wall of transgenic rice plants overexpressing individual ARAF full-length cDNA (OsARAF1 FOX and OsARAF3-FOX) decreased 25% and 20% compared to the control and the amount of glucose increased by 28.2% and 34.2%, respectively. We studied modifications of cell wall polysaccharides at the cellular level by comparing histochemical cellulose staining patterns and immunolocalization patterns using antibodies raised against alpha-(1,5)-linked l-Ara (LM6) and beta-(1,4)-linked d-Xyl (LM10 and LM11) residues. However, they showed no visible phenotype. Our results suggest that the balance between arabinoxylan and cellulose might maintain the cell wall network. Moreover, ARAF overexpression in rice effectively leads to an increase in cellulose accumulation and saccharification efficiency, which can be used to produce bioethanol. PMID- 24223787 TI - Hepatitis C transmission and treatment in contact networks of people who inject drugs. AB - Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective. PMID- 24223788 TI - Prolonged bioluminescence monitoring in mouse ex vivo bone culture revealed persistent circadian rhythms in articular cartilages and growth plates. AB - The bone is a metabolically active organ which undergoes repeated remodeling cycles of bone resorption and formation. In this study, we revealed a robust and extremely long-lasting circadian rhythm in ex vivo culture maintained for over six months from the femoral bone of a PERIOD2(Luciferase) mouse. Furthermore, we also identified robust circadian clocks in flat bones. High- or low-magnification real-time bioluminescence microscopic imaging revealed that the robust circadian rhythms emanated from the articular cartilage and the epiphyseal cartilage within the growth plate of juvenile animals. Stimulation by forskolin or dexamethasone treatment caused type 0 phase resetting, indicating canonical entraining properties of the bone clock. Together, our findings from long-term ex vivo culture revealed that "tissue-autonomous" circadian rhythm in the articular cartilage and the growth plate of femoral bone functions for several months even in an organ culture condition, and provided a useful in vitro assay system investigating the role of the biological clock in bone formation or development. PMID- 24223789 TI - Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns. AB - A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe. PMID- 24223791 TI - Non-uniform dispersion of the source-sink relationship alters wavefront curvature. AB - The distribution of cellular source-sink relationships plays an important role in cardiac propagation. It can lead to conduction slowing and block as well as wave fractionation. It is of great interest to unravel the mechanisms underlying evolution in wavefront geometry. Our goal is to investigate the role of the source-sink relationship on wavefront geometry using computer simulations. We analyzed the role of variability in the microscopic source-sink relationship in driving changes in wavefront geometry. The electrophysiological activity of a homogeneous isotropic tissue was simulated using the ten Tusscher and Panfilov 2006 action potential model and the source-sink relationship was characterized using an improved version of the Romero et al. safety factor formulation (SFm2). Our simulations reveal that non-uniform dispersion of the cellular source-sink relationship (dispersion along the wavefront) leads to alterations in curvature. To better understand the role of the source-sink relationship in the process of wave formation, the electrophysiological activity at the initiation of excitation waves in a 1D strand was examined and the source-sink relationship was characterized using the two recently updated safety factor formulations: the SFm2 and the Boyle-Vigmond (SFVB) definitions. The electrophysiological activity at the initiation of excitation waves was intimately related to the SFm2 profiles, while the SFVB led to several counterintuitive observations. Importantly, with the SFm2 characterization, a critical source-sink relationship for initiation of excitation waves was identified, which was independent of the size of the electrode of excitation, membrane excitability, or tissue conductivity. In conclusion, our work suggests that non-uniform dispersion of the source-sink relationship alters wavefront curvature and a critical source-sink relationship profile separates wave expansion from collapse. Our study reinforces the idea that the safety factor represents a powerful tool to study the mechanisms of cardiac propagation in silico, providing a better understanding of cardiac arrhythmias and their therapy. PMID- 24223790 TI - Culture of airway epithelial cells from neonates sampled within 48-hours of birth. AB - INTRODUCTION: Little is known about how neonatal airway epithelial cell phenotype impacts on respiratory disease in later life. This study aimed to establish a methodology to culture and characterise neonatal nasal epithelial cells sampled from healthy, non-sedated infants within 48 hours of delivery. METHODS: Nasal epithelial cells were sampled by brushing both nostrils with an interdental brush, grown to confluence and sub-cultured. Cultured cells were characterised morphologically by light and electron microscopy and by immunocytochemistry. As an exemplar pro-inflammatory chemokine, IL-8 concentrations were measured in supernatants from unstimulated monolayers and after exposure to IL-1beta/TNF alpha or house dust mite extract. RESULTS: Primary cultures were successfully established in 135 (91%) of 149 neonatal samples seeded, with 79% (n = 117) successfully cultured to passage 3. The epithelial lineage of the cells was confirmed by morphological analysis and immunostaining. Constitutive IL-8 secretion was observed and was upregulated by IL-1beta/TNF-alpha or house dust mite extract in a dose dependent manner. CONCLUSION: We describe a safe, minimally invasive method of culturing nasal epithelial cells from neonates suitable for functional cell analysis offering an opportunity to study "naive" cells that may prove useful in elucidating the role of the epithelium in the early origins of asthma and/or allergic rhinitis. PMID- 24223792 TI - Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium. AB - BACKGROUND: Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells. METHODS: Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome. RESULTS: Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis. CONCLUSION: Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker. PMID- 24223793 TI - Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor. AB - BACKGROUND: Hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, enhances hepatocyte function without stimulating proliferation, depending on the physiological conditions. p53, a transcription factor, suppresses the cell proliferation by expressing p21(WAF1/CIP1) in various tissues. AIM: To investigate the mechanism through which the hepatocytes maintain mitotically quiescent even in the presence of HGF. METHODS: We studied the relationship between p53 and p21 expression and the effect of p53-p21 axis on hepatocyte proliferation in primary cultured rat hepatocytes stimulated by HGF. Hepatic p21 levels are determined serially after partial hepatectomy or sham operation in rats. RESULTS: DNA synthesis was markedly increased by HGF addition in rat hepatocytes cultured at low density but not at high density. Cellular p53 levels increased in the hepatocytes cultured at both the densities. p21 levels were increased and correlated with cellular p53 levels in hepatocytes cultured at high density but not at low density. When the activity of p53 was suppressed by a chemical inhibitor for p53, cellular p21 levels were reduced, and DNA synthesis was increased. Similarly, p21 antisense oligonucleotide increased the DNA synthesis. In rats after partial hepatectomy, transient elevation of hepatic p21 levels was observed. In contrast, in sham-operated rats, hepatic p21 levels were increased on sustained time scales. CONCLUSION: p53-related induction of p21 may suppress hepatocyte proliferation in the presence of HGF in the setting that mitogenic activity of HGF is not elicitable. PMID- 24223794 TI - Proteomic and immunochemical characterization of glutathione transferase as a new allergen of the nematode Ascaris lumbricoides. AB - Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy. Glutathione transferases (GSTs) from cockroach and house dust mites are clinically relevant allergens and comparative studies between them and the GST from A. lumbricoides (GSTA) are necessary to evaluate their allergenicity. We sought to analyze the allergenic potential of GSTA in connection with the IgE response to non-parasitic GSTs. IgE to purified GSTs from Ascaris (nGSTA and rGSTA), house dust mites (rDer p 8, nBlo t 8 and rBlo t 8), and cockroach (rBla g 5) was measured by ELISA in subjects from Cartagena, Colombia. Also, multidimensional proteomic approaches were used to study the extract of A. lumbricoides and investigate the existence of GST isoforms. We found that among asthmatics, the strength of IgE levels to GSTA was significantly higher than to mite and cockroach GSTs, and there was a strong positive correlation between IgE levels to these molecules. Specific IgE to GSTA was found in 13.2% of controls and 19.5% of asthmatics. In addition nGSTA induced wheal and flare in skin of sensitized asthmatics indicating that it might be of clinical relevance for some patients. Frequency and IgE levels to GSTA were higher in childhood and declined with age. At least six GST isoforms in A. lumbricoides bind human IgE. Four isoforms were the most abundant and several amino acid substitutions were found, mainly on the N-terminal domain. In conclusion, a new allergenic component of Ascaris has been discovered; it could have clinical impact in allergic patients and influence the diagnosis of mite and cockroach allergy in tropical environments. PMID- 24223795 TI - Epidemiology and risk factors of cervical spine injury during heating season in the patients with cervical trauma: a cross-sectional study. AB - PURPOSE: The purpose of this study was to describe the epidemiology of cervical spine injury in the patients with cervical trauma and analyze its associated risk factors during the special heating season in North China. METHODS: This cross sectional study investigated predictors for cervical spine injury in cervical trauma patients using retrospectively collected data of Hebei Provincial Orthopaedic Hospital from 11/2011 to 02/2012, and 11/2012 to 02/2013. Binary logistic regression analysis was used to determine risk factors for cervical fractures/dislocations or cord injury. RESULTS: A total of 106 patients were admitted into this study. Of all, 34 patients (32.1%) were treated from 11/2011 to 02/2012 and 72 patients (67.9%) from 11/2012 to 02/2013. The mean age was 41.9+/-13.3 years old; 85 patients (80.2%) were male and 82 (77.4%) from rural areas. Eighty patients (75.5%) were caused by fall including 45 (42.5%) by severe fall (>2 m). Sixty-five patients (61.3%) of all suffered injuries to other body regions and 32 (30.2%) got head injury. Thirty-one patients (29.2%) sustained cervical cord injury with cervical fractures/dislocations. Twenty-six (83.9%) of cervical cord injury patients were from rural areas and 24 (77.4%) of those resulted from fall including 15 (48.4%) from severe fall (>2 m). Logistic regression displayed that age (OR, 1.47; 95% CI, 1.05-2.07), head injury (OR, 5.63; 95% CI, 2.23-14.26), were risk factors for cervical cord injury and snowing (OR, 8.25; 95% CI, 2.26-30.15) was a risk factor for cervical spine injury due to severe fall (>2 m). CONCLUSIONS: The elder male patients and patients with head trauma are high-risk population for cervical cord injury. As a seasonal factor, snowing during heating season is of note a risk factor for cervical spine injury resulting from severe fall (>2 m) in the patients with cervical trauma in North China. PMID- 24223796 TI - The economic burden of malaria on households and the health system in Enugu State southeast Nigeria. AB - BACKGROUND: Malaria is the number one public health problem in Nigeria, responsible for about 30% of deaths in under-fives and 25% of deaths in infants and 11% maternal mortality. This study estimated the economic burden of malaria in Nigeria using the cost of illness approach. METHODS: A cross-sectional study was undertaken in two malaria holo-endemic communities in Nigeria, involving both community and hospital based surveys. A random sample of 500 households was interviewed using interviewer administered questionnaire. In addition, 125 exit interviews for inpatient department stays (IPD) and outpatient department visits (OPD) were conducted and these were complemented with data abstraction from 125 patient records. RESULTS: From the household survey, over half of the households (57.6%) had an episode of malaria within one month to the date of the interview. The average household expenditure per case was 12.57US$ and 23.20US$ for OPD and IPD respectively. Indirect consumer costs of treatment were higher than direct consumer medical costs. From a health system perspective, the recurrent provider costs per case was 30.42 US$ and 48.02 US$ for OPD and IPD while non recurrent provider costs were 133.07US$ and 1857.15US$ for OPD and IPD. The mode of payment was mainly through out-of-pocket spending (OOPS). CONCLUSION: Private expenditure on treatment of malaria constitutes a high economic burden to households and to the health system. Removal of user fees and interventions that will decrease the use of OOPS for treatment of malaria will significantly decrease the economic burden of malaria to both households and the health system. PMID- 24223798 TI - EGFR T790M mutation as a possible target for immunotherapy; identification of HLA A*0201-restricted T cell epitopes derived from the EGFR T790M mutation. AB - Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib, has achieved high clinical response rates in patients with non-small cell lung cancers (NSCLCs). However, over time, most tumors develop acquired resistance to EGFR-TKIs, which is associated with the secondary EGFR T790M resistance mutation in about half the cases. Currently there are no effective treatment options for patients with this resistance mutation. Here we identified two novel HLA-A*0201 (A2)-restricted T cell epitopes containing the mutated methionine residue of the EGFR T790M mutation, T790M-5 (MQLMPFGCLL) and T790M-7 (LIMQLMPFGCL), as potential targets for EGFR-TKI resistant patients. When peripheral blood cells were repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific IFN-gamma secretion, T cell lines responsive to T790M-5 and T790M-7 were established in 5 of 6 (83%) and 3 of 6 (50%) healthy donors, respectively. Additionally, the T790M 5- and T790M-7-specific T cell lines displayed an MHC class I-restricted reactivity against NSCLC cell lines expressing both HLA-A2 and the T790M mutation. Interestingly, the NSCLC patients with antigen-specific T cell responses to these epitopes showed a significantly less frequency of EGFR-T790M mutation than those without them [1 of 7 (14%) vs 9 of 15 (60%); chi-squared test, p = 0.0449], indicating the negative correlation between the immune responses to the EGFR-T790M-derived epitopes and the presence of EGFR-T790M mutation in NSCLC patients. This finding could possibly be explained by the hypothesis that immune responses to the mutated neo-antigens derived from T790M might prevent the emergence of tumor cell variants with the T790M resistance mutation in NSCLC patients during EGFR-TKI treatment. Together, our results suggest that the identified T cell epitopes might provide a novel immunotherapeutic approach for prevention and/or treatment of EGFR-TKI resistance with the secondary EGFR T790M resistance mutation in NSCLC patients. PMID- 24223797 TI - Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. AB - Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9 tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex dependent psychophysiological alterations and they reveal functional interactions between the two drugs. PMID- 24223800 TI - A solution to the challenge of optimization on ''golf-course''-like fitness landscapes. AB - Genetic algorithms (GAs) have been used to find efficient solutions to numerous fundamental and applied problems. While GAs are a robust and flexible approach to solve complex problems, there are some situations under which they perform poorly. Here, we introduce a genetic algorithm approach that is able to solve complex tasks plagued by so-called ''golf-course''-like fitness landscapes. Our approach, which we denote variable environment genetic algorithms (VEGAs), is able to find highly efficient solutions by inducing environmental changes that require more complex solutions and thus creating an evolutionary drive. Using the density classification task, a paradigmatic computer science problem, as a case study, we show that more complex rules that preserve information about the solution to simpler tasks can adapt to more challenging environments. Interestingly, we find that conservative strategies, which have a bias toward the current state, evolve naturally as a highly efficient solution to the density classification task under noisy conditions. PMID- 24223799 TI - Alternative signaling pathways as potential therapeutic targets for overcoming EGFR and c-Met inhibitor resistance in non-small cell lung cancer. AB - The use of tyrosine kinase inhibitors (TKIs) against EGFR/c-Met in non-small cell lung cancer (NSCLC) has been shown to be effective in increasing patient progression free survival (PFS), but their efficacy is limited due to the development of resistance and tumor recurrence. Therefore, understanding the molecular mechanisms underlying development of drug resistance in NSCLC is necessary for developing novel and effective therapeutic approaches to improve patient outcome. This study aims to understand the mechanism of EGFR/c-Met tyrosine kinase inhibitor (TKI) resistance in NSCLC. H2170 and H358 cell lines were made resistant to SU11274, a c-Met inhibitor, and erlotinib, an EGFR inhibitor, through step-wise increases in TKI exposure. The IC50 concentrations of resistant lines exhibited a 4-5 and 11-22-fold increase for SU11274 and erlotinib, respectively, when compared to parental lines. Furthermore, mTOR and Wnt signaling was studied in both cell lines to determine their roles in mediating TKI resistance. We observed a 2-4-fold upregulation of mTOR signaling proteins and a 2- to 8-fold upregulation of Wnt signaling proteins in H2170 erlotinib and SU11274 resistant cells. H2170 and H358 cells were further treated with the mTOR inhibitor everolimus and the Wnt inhibitor XAV939. H358 resistant cells were inhibited by 95% by a triple combination of everolimus, erlotinib and SU11274 in comparison to 34% by a double combination of these drugs. Parental H2170 cells displayed no sensitivity to XAV939, while resistant cells were significantly inhibited (39%) by XAV939 as a single agent, as well as in combination with SU11274 and erlotinib. Similar results were obtained with H358 resistant cells. This study suggests a novel molecular mechanism of drug resistance in lung cancer. PMID- 24223801 TI - Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development. AB - RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (P<0.05). RhoB expression decreases significantly from stage II (71.4%) to stage III (43.5%) to stage IV (18.2%, P<0.05). TSA can both significantly revive the RhoB gene and mediate apoptosis of ovarian cancer cells, but 5-Aza couldn't. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies. PMID- 24223802 TI - Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress. AB - Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations. PMID- 24223803 TI - Metastasis suppressor microRNA-335 targets the formin family of actin nucleators. AB - MiRNAs can have pleiotropic effects by targeting multiple genes belonging to diverse signalling networks. Alternatively, miRNAs can enhance the potency of their cellular effects by targeting multiple genes within the same genetic pathway. Previously, we and others have demonstrated that miR-335 is a potent suppressor of tumour cell migration, invasion and metastasis, in part by targeting several genes involved in these cellular processes, including ROCK1, MAPK1, LRG1, SP1 and SOX4. Here, we demonstrate that direct targeting of multiple members of the formin family of actin nucleators contributes to the inhibitory effects of miR-335 in neuroblastoma cells. We demonstrate that miR-335 regulates the expression of at least five formin family members and validate three family members, FMNL3, FMN2 and DAAM2, as direct targets of miR-335. The contribution of the formin family genes to cancer progression and metastasis has recently begun to emerge and here we demonstrate for the first time the ability of FMN2 and DAAM2 to regulate tumour cell migration and invasion, using siRNA-mediated inhibition of each of these formin genes. Finally, we demonstrate that the formin genes, in particular FMNL3, are responsible for the protrusion of actin-rich filopodia structures that contribute to the enhanced migratory and invasive potential associated with reduced expression of miR-335. Thus, direct targeting of the formin family contributes to the metastasis suppressing abilities of miR 335 by providing a direct regulatory link to the actin assembly machinery of the cell. We conclude that miR-335 is a master regulator of tumour cell migration and invasion by directly targeting a plethora of genes that effectively control cell migratory processes. PMID- 24223804 TI - Hyperthermia in human ischemic and hemorrhagic stroke: similar outcome, different mechanisms. AB - Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax <37.5 degrees C and Tmax >=37.5 degrees C, up to reach 50 patients per subgroup of temperature for both IS and ICH patients. Body temperature was determined at admission and every 4 hours during the first 48 hours. Main outcome variable was poor functional outcome (modified Rankin scale score >2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax >=37.5 degrees C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73-41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32-13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00-1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01-1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00-1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13-1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different. PMID- 24223805 TI - Social influence and the collective dynamics of opinion formation. AB - Social influence is the process by which individuals adapt their opinion, revise their beliefs, or change their behavior as a result of social interactions with other people. In our strongly interconnected society, social influence plays a prominent role in many self-organized phenomena such as herding in cultural markets, the spread of ideas and innovations, and the amplification of fears during epidemics. Yet, the mechanisms of opinion formation remain poorly understood, and existing physics-based models lack systematic empirical validation. Here, we report two controlled experiments showing how participants answering factual questions revise their initial judgments after being exposed to the opinion and confidence level of others. Based on the observation of 59 experimental subjects exposed to peer-opinion for 15 different items, we draw an influence map that describes the strength of peer influence during interactions. A simple process model derived from our observations demonstrates how opinions in a group of interacting people can converge or split over repeated interactions. In particular, we identify two major attractors of opinion: (i) the expert effect, induced by the presence of a highly confident individual in the group, and (ii) the majority effect, caused by the presence of a critical mass of laypeople sharing similar opinions. Additional simulations reveal the existence of a tipping point at which one attractor will dominate over the other, driving collective opinion in a given direction. These findings have implications for understanding the mechanisms of public opinion formation and managing conflicting situations in which self-confident and better informed minorities challenge the views of a large uninformed majority. PMID- 24223806 TI - Using ecological momentary assessment in testing the effectiveness of an alcohol intervention: a two-arm parallel group randomized controlled trial. AB - BACKGROUND: Alcohol consumption of college students has a fluctuating nature, which might impact the measurement of intervention effects. By using 25 follow-up time-points, this study tested whether intervention effects are robust or might vary over time. METHODS: Data were used from a two-arm parallel group randomized controlled trial applying ecological momentary assessment (EMA) with 30 data time points in total. Students between 18 and 24 years old who reported heavy drinking in the past six months and who were ready to change their alcohol consumption were randomly assigned to the experimental (n = 456: web-based brief alcohol intervention) and control condition (n = 451: no intervention). Outcome measures were weekly alcohol consumption, frequency of binge drinking, and heavy drinking status. RESULTS: According to the intention-to-treat principle, regression analyses revealed that intervention effects on alcohol consumption varied when exploring multiple follow-up time-points. Intervention effects were found for a) weekly alcohol consumption at 1, 2, 3, 4, and 7 weeks follow-up, b) frequency of binge drinking at 1, 2, 7, and 12 weeks follow-up, and c) heavy drinking status at 1, 2, 7, and 16 weeks follow-up. CONCLUSIONS: This research showed that the commonly used one and six month follow-up time-points are relatively arbitrary and not using EMA might bring forth erroneous conclusions on the effectiveness of interventions. Therefore, future trials in alcohol prevention research and beyond are encouraged to apply EMA when assessing outcome measures and intervention effectiveness. TRIAL REGISTRATION: Netherlands Trial Register NTR2665. PMID- 24223807 TI - Correlated biogeographic variation of magnesium across trophic levels in a terrestrial food chain. AB - Using samples from eastern China (c. 25 - 41 degrees N and 99 - 123 degrees E) and from a common garden experiment, we investigate how Mg concentration varies with climate across multiple trophic levels. In soils, plant tissue (Oriental oak leaves and acorns), and a specialist acorn predator (the weevil Curculio davidi), Mg concentration increased significantly with different slopes from south to north, and generally decreased with both mean annual temperature (MAT) and precipitation (MAP). In addition, soil, leaf, acorn and weevil Mg showed different strengths of association and sensitivity with climatic factors, suggesting that distinct mechanisms may drive patterns of Mg variation at different trophic levels. Our findings provide a first step toward determining whether anticipated changes in temperature and precipitation due to climate change will have important consequences for the bioavailability and distribution of Mg in food chain. PMID- 24223808 TI - Autologous antibody capture to enrich immunogenic viruses for viral discovery. AB - Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics. PMID- 24223809 TI - RNA-Seq analysis reveals candidate genes for ontogenic resistance in Malus Venturia pathosystem. AB - Ontogenic scab resistance in apple leaves and fruits is a horizontal resistance against the plant pathogen Venturia inaequalis and is expressed as a decrease in disease symptoms and incidence with the ageing of the leaves. Several studies at the biochemical level tried to unveil the nature of this resistance; however, no conclusive results were reported. We decided therefore to investigate the genetic origin of this phenomenon by performing a full quantitative transcriptome sequencing and comparison of young (susceptible) and old (ontogenic resistant) leaves, infected or not with the pathogen. Two time points at 72 and 96 hours post-inoculation were chosen for RNA sampling and sequencing. Comparison between the different conditions (young and old leaves, inoculated or not) should allow the identification of differentially expressed genes which may represent different induced plant defence reactions leading to ontogenic resistance or may be the cause of a constitutive (uninoculated with the pathogen) shift toward resistance in old leaves. Differentially expressed genes were then characterised for their function by homology to A. thaliana and other plant genes, particularly looking for genes involved in pathways already suspected of appertaining to ontogenic resistance in apple or other hosts, or to plant defence mechanisms in general. IN THIS WORK, FIVE CANDIDATE GENES PUTATIVELY INVOLVED IN THE ONTOGENIC RESISTANCE OF APPLE WERE IDENTIFIED: a gene encoding an "enhanced disease susceptibility 1 protein" was found to be down-regulated in both uninoculated and inoculated old leaves at 96 hpi, while the other four genes encoding proteins (metallothionein3-like protein, lipoxygenase, lipid transfer protein, and a peroxidase 3) were found to be constitutively up-regulated in inoculated and uninoculated old leaves. The modulation of the five candidate genes has been validated using the real-time quantitative PCR. Thus, ontogenic resistance may be the result of the corresponding up- and down-regulation of these genes. PMID- 24223810 TI - Epigenetic profiles in children with a neural tube defect; a case-control study in two populations. AB - Folate deficiency is implicated in the causation of neural tube defects (NTDs). The preventive effect of periconceptional folic acid supplement use is partially explained by the treatment of a deranged folate-dependent one carbon metabolism, which provides methyl groups for DNA-methylation as an epigenetic mechanism. Here, we hypothesize that variations in DNA-methylation of genes implicated in the development of NTDs and embryonic growth are part of the underlying mechanism. In 48 children with a neural tube defect and 62 controls from a Dutch case-control study and 34 children with a neural tube defect and 78 controls from a Texan case-control study, we measured the DNA-methylation levels of imprinted candidate genes (IGF2-DMR, H19, KCNQ1OT1) and non-imprinted genes (the LEKR/CCNL gene region associated with birth weight, and MTHFR and VANGL1 associated with NTD). We used the MassARRAY EpiTYPER assay from Sequenom for the assessment of DNA-methylation. Linear mixed model analysis was used to estimate associations between DNA-methylation levels of the genes and a neural tube defect. In the Dutch study group, but not in the Texan study group we found a significant association between the risk of having an NTD and DNA methylation levels of MTHFR (absolute decrease in methylation of -0.33% in cases, P-value = 0.001), and LEKR/CCNL (absolute increase in methylation: 1.36% in cases, P-value = 0.048), and a borderline significant association for VANGL (absolute increase in methylation: 0.17% in cases, P-value = 0.063). Only the association between MTHFR and NTD-risk remained significant after multiple testing correction. The associations in the Dutch study were not replicated in the Texan study. We conclude that the associations between NTDs and the methylation of the MTHFR gene, and maybe VANGL and LEKKR/CNNL, are in line with previous studies showing polymorphisms in the same genes in association with NTDs and embryonic development, respectively. PMID- 24223811 TI - Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture. AB - Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2*10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K 1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1beta, TNF-alpha angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future. PMID- 24223812 TI - The epidemiology and geographic distribution of relapsing fever borreliosis in West and North Africa, with a review of the Ornithodoros erraticus complex (Acari: Ixodida). AB - BACKGROUND: Relapsing fever is the most frequent bacterial disease in Africa. Four main vector / pathogen complexes are classically recognized, with the louse Pediculus humanus acting as vector for B. recurrentis and the soft ticks Ornithodoros sonrai, O. erraticus and O. moubata acting as vectors for Borrelia crocidurae, B. hispanica and B. duttonii, respectively. Our aim was to investigate the epidemiology of the disease in West, North and Central Africa. METHODS AND FINDINGS: From 2002 to 2012, we conducted field surveys in 17 African countries and in Spain. We investigated the occurrence of Ornithodoros ticks in rodent burrows in 282 study sites. We collected 1,629 small mammals that may act as reservoir for Borrelia infections. Using molecular methods we studied genetic diversity among Ornithodoros ticks and Borrelia infections in ticks and small mammals. Of 9,870 burrows investigated, 1,196 (12.1%) were inhabited by Ornithodoros ticks. In West Africa, the southern and eastern limits of the vectors and Borrelia infections in ticks and small mammals were 13 degrees N and 01 degrees E, respectively. Molecular studies revealed the occurrence of nine different Ornithodoros species, including five species new for science, with six of them harboring Borrelia infections. Only B. crocidurae was found in West Africa and three Borrelia species were identified in North Africa: B. crocidurae, B. hispanica, and B. merionesi. CONCLUSIONS: Borrelia Spirochetes responsible for relapsing fever in humans are highly prevalent both in Ornithodoros ticks and small mammals in North and West Africa but Ornithodoros ticks seem absent south of 13 degrees N and small mammals are not infected in these regions. The number of Ornithodoros species acting as vector of relapsing fever is much higher than previously known. PMID- 24223813 TI - Functional characterization of Dihydroflavonol-4-reductase in anthocyanin biosynthesis of purple sweet potato underlies the direct evidence of anthocyanins function against abiotic stresses. AB - Dihydroflavonol-4-reductase (DFR) is a key enzyme in the catalysis of the stereospecific reduction of dihydroflavonols to leucoanthocyanidins in anthocyanin biosynthesis. In the purple sweet potato (Ipomoea batatas Lam.) cv. Ayamurasaki, expression of the IbDFR gene was strongly associated with anthocyanin accumulation in leaves, stems and roots. Overexpression of the IbDFR in Arabidopsis tt3 mutants fully complemented the pigmentation phenotype of the seed coat, cotyledon and hypocotyl. Downregulation of IbDFR expression in transgenic sweet potato (DFRi) using an RNAi approach dramatically reduced anthocyanin accumulation in young leaves, stems and storage roots. In contrast, the increase of flavonols quercetin-3-O-hexose-hexoside and quercetin-3-O glucoside in the leaves and roots of DFRi plants is significant. Therefore, the metabolic pathway channeled greater flavonol influx in the DFRi plants when their anthocyanin and proanthocyanidin accumulation were decreased. These plants also displayed reduced antioxidant capacity compared to the wild type. After 24 h of cold treatment and 2 h recovery, the wild-type plants were almost fully restored to the initial phenotype compared to the slower recovery of DFRi plants, in which the levels of electrolyte leakage and hydrogen peroxide accumulation were dramatically increased. These results provide direct evidence of anthocyanins function in the protection against oxidative stress in the sweet potato. The molecular characterization of the IbDFR gene in the sweet potato not only confirms its important roles in flavonoid metabolism but also supports the protective function of anthocyanins of enhanced scavenging of reactive oxygen radicals in plants under stressful conditions. PMID- 24223814 TI - Association between adiponectin concentrations and cardiovascular disease in diabetic patients: a systematic review and meta-analysis. AB - BACKGROUND: This systematic review and meta-analysis of prospective studies evaluates the association between adiponectin concentrations and risk of cardiovascular disease (CVD) in individuals with diabetes mellitus (DM). METHODS: PubMed and Embase were searched for prospective studies on the association of adiponectin concentrations and risk of CVD up to June 2013. Random-effect model was selected to pool the relative risk (RR) and 95% CI. RESULTS: Five prospective cohort studies and one nested case-control studies met the included criterion. The estimated summary RR and 95% CI of five prospective cohort studies for type 2 diabetes comparing top vs low tertile of adiponectin concentrations was 0.99 (95% CI: 0.67-1.45), with significant heterogeneity between studies (p = 0.037, I (2) = 60.9%). This heterogeneity was explained by one study conducted in Korean. CONCLUSIONS: This study represents the first meta-analysis between adiponectin levels and CVD in diabetic patients and indicated no association was found. This result should be verified further by large sample size, long duration of follow up, and well-designed prospective clinical trials. PMID- 24223815 TI - Left radial access is preferable to right radial access for the diagnostic or interventional coronary procedures: a meta-analysis involving 22 randomized clinical trials and 10287 patients. AB - OBJECTIVE: The transradial approach has been used extensively for both diagnostic and interventional coronary procedures; however, there is no universal consensus hitherto on the optimal choice of radial access from either the left or the right artery. We therefore sought to meta-analyze available randomized clinical trials to compare the left with the right radial access for the diagnostic or interventional coronary procedures. METHODS AND RESULTS: Four electronic databases including the PubMed, EMBASE, Wanfang, and CNKI were searched up to April 2013. In total, there were 22 qualified randomized trials involving 5317 and 4970 patients assigned to the left and the right radial accesses, respectively. Data were extracted independently by two investigators. Analyses of the full data set indicated significant reductions in fluoroscopy time (seconds) (weighted mean difference; 95% confidence interval; P: -36.18; -53.28 to -18.53; <0.0005) and contrast use (mL) (-2.88; -5.41 to -0.34; 0.026) in patients with the left radial access compared to those with the right radial access, and there was strong evidence of heterogeneity but low probability of publication bias. The failure rate of radial access from the left was relatively lower than that from the right (odds ratio: 0.83; 95% confidence interval: 0.68-1.01; P = 0.064). Further in meta-regression analyses, body mass index was found to be a potential source of heterogeneity for both fluoroscopy time (regression coefficient: 35.85; P = 0.025) and catheter number (regression coefficient: 0.35; P = 0.018). CONCLUSIONS: Our findings demonstrate that left radial access is preferable to right radial access in terms of fluoroscopy time and contrast use for the diagnostic or interventional coronary procedures. The import of this study lies in its great shock to the concept of convenient radial access from the right artery. PMID- 24223816 TI - Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence. AB - Cell-cell communication within the follicle involves many signaling molecules, and this process may be mediated by secretion and uptake of exosomes that contain several bioactive molecules including extra-cellular miRNAs. Follicular fluid and cells from individual follicles of cattle were grouped based on Brilliant Cresyl Blue (BCB) staining of the corresponding oocytes. Both Exoquick precipitation and differential ultracentrifugation were used to separate the exosome and non exosomal fraction of follicular fluid. Following miRNA isolation from both fractions, the human miRCURY LNATM Universal RT miRNA PCR array system was used to profile miRNA expression. This analysis found that miRNAs were present in both exosomal and non-exosomal fraction of bovine follicular fluid. We found 25 miRNAs differentially expressed (16 up and 9 down) in exosomes and 30 miRNAs differentially expressed (21 up and 9 down) in non-exosomal fraction of follicular fluid in comparison of BCB- versus BCB+ oocyte groups. Expression of selected miRNAs was detected in theca, granulosa and cumulus oocyte complex. To further explore the potential roles of these follicular fluid derived extra cellular miRNAs, the potential target genes were predicted, and functional annotation and pathway analysis revealed most of these pathways are known regulators of follicular development and oocyte growth. In order to validate exosome mediated cell-cell communication within follicular microenvironment, we demonstrated uptake of exosomes and resulting increase of endogenous miRNA level and subsequent alteration of mRNA levels in follicular cells in vitro. This study demonstrates for the first time, the presence of exosome or non-exosome mediated transfer of miRNA in the bovine follicular fluid, and oocyte growth dependent variation in extra-cellular miRNA signatures in the follicular environment. PMID- 24223817 TI - Metagenomic insights into the carbohydrate-active enzymes carried by the microorganisms adhering to solid digesta in the rumen of cows. AB - The ruminal microbial community is a unique source of enzymes that underpin the conversion of cellulosic biomass. In this study, the microbial consortia adherent on solid digesta in the rumen of Jersey cattle were subjected to an activity based metagenomic study to explore the genetic diversity of carbohydrolytic enzymes in Jersey cows, with a particular focus on cellulases and xylanases. Pyrosequencing and bioinformatic analyses of 120 carbohydrate-active fosmids identified genes encoding 575 putative Carbohydrate-Active Enzymes (CAZymes) and proteins putatively related to transcriptional regulation, transporters, and signal transduction coupled with polysaccharide degradation and metabolism. Most of these genes shared little similarity to sequences archived in databases. Genes that were predicted to encode glycoside hydrolases (GH) involved in xylan and cellulose hydrolysis (e.g., GH3, 5, 9, 10, 39 and 43) were well represented. A new subfamily (S-8) of GH5 was identified from contigs assigned to Firmicutes. These subfamilies of GH5 proteins also showed significant phylum-dependent distribution. A number of polysaccharide utilization loci (PULs) were found, and two of them contained genes encoding Sus-like proteins and cellulases that have not been reported in previous metagenomic studies of samples from the rumens of cows or other herbivores. Comparison with the large metagenomic datasets previously reported of other ruminant species (or cattle breeds) and wallabies showed that the rumen microbiome of Jersey cows might contain differing CAZymes. Future studies are needed to further explore how host genetics and diets affect the diversity and distribution of CAZymes and utilization of plant cell wall materials. PMID- 24223818 TI - Chemokine receptors CCR6 and CXCR3 are necessary for CD4(+) T cell mediated ocular surface disease in experimental dry eye disease. AB - CD4(+) T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4(+) T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN gamma and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4(+) T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4(+) T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease. PMID- 24223819 TI - Control efficacy of annual community-wide treatment against Schistosoma japonicum in China: a meta-analysis. AB - BACKGROUNDS: Human schistosomiasis is caused by schistosome, with annual loss of over 70 million disability adjusted life years in the world. China is endemic with Schistosoma japonicum and large-scale chemotherapy with praziquantel has become the mainstay of control in China since 1990s. However, the control effects of mass treatment in the field have been uneven. Moreover, mass treatment has come into a wide use in other countries with limited health resources. Therefore, a better understanding of the control effect of mass treatment is in an urgent need. METHODS: We performed a systematic search of the literature to investigate the control efficiency of annual community-wide treatment (ACWT, treatment to an entire community without any preliminary screening) with a single dose of PZQ (40 mg kg(-1) bodyweight) against schistosome in humans in China. Three Chinese literature databases, including China National Knowledge Infrastructure, WanFang and Chinese Scientific Journal Databases, and the PubMed were searched. Pooled prevalence ratios (prevalence after to before treatment) were used to assess effect. Our protocol is available on PROSPERO (No. CRD42013003628). RESULTS: 22 articles were included. Meta-analyses on data from 18 studies on one round of ACWT, 17 studies on two consecutive rounds and 6 studies on three consecutive rounds were performed. The results showed control effects of ACWT plus other measures were statistically significant, with prevalence ratios being 0.38 (0.31, 0.46) for one round, 0.28 (0.22, 0.35) for two rounds and 0.22 (0.10, 0.46) for three rounds. When ACWT was performed alone or with health education only, the values for one and two rounds were 0.389 (0.307, 0.492) and 0.348 (0.300, 0.403), respectively. CONCLUSIONS: The control effect of ACWT alone or with other measures is significant and increases with the number of rounds. Such program is recommended in high endemic areas and the criteria yet merit further assessment. PMID- 24223820 TI - Preserved antigen-specific immune response in patients with multiple sclerosis responding to IFNbeta-therapy. AB - BACKGROUND: Interferon-beta (IFNbeta) regulates the expression of a complex set of pro- as well as anti-inflammatory genes. In cohorts of MS patients unstratified for therapeutic response to IFNbeta, normal vaccine-specific immune responses have been observed. Data capturing antigen-specific immune responses in cohorts of subjects defined by response to IFNbeta-therapy are not available. OBJECTIVE: To assess antigen-specific immune responses in a cohort of MS patients responding clinically and radiologically to IFNbeta. METHODS: In 26 MS patients, clinical and MRI disease activity were assessed before and under treatment with IFNbeta. Humoral and cellular immune response to influenza vaccine was prospectively characterized in these individuals, and 33 healthy controls by influenza-specific Enzyme-Linked Immunosorbent Assay (ELISA) and Enzyme Linked Immuno Spot Technique (ELISPOT). RESULTS: Related to pre-treatment disease activity, IFNbeta reduced clinical and radiological MS disease-activity. Following influenza vaccination, frequencies of influenza-specific T cells and concentrations of anti-influenza A and B IgM and IgG increased comparably in MS patients and in healthy controls. CONCLUSIONS: By showing in a cohort of MS patients responding to IFNbeta vaccine-specific immune responses comparable to controls, this study indicates that antigen-specific immune responses can be preserved under successful IFNbeta-therapy. PMID- 24223821 TI - Directional locomotion of C. elegans in the absence of external stimuli. AB - Many organisms respond to food deprivation by altering their pattern of movement, often in ways that appear to facilitate dispersal. While the behavior of the nematode C. elegans in the presence of attractants has been characterized, long range movement in the absence of external stimuli has not been examined in this animal. Here we investigate the movement pattern of individual C. elegans over times of ~1 hour after removal from food, using two custom imaging set-ups that allow us to track animals on large agar surfaces of 22 cm*22 cm. We find that a sizeable fraction of the observed trajectories display directed motion over tens of minutes. Remarkably, this directional persistence is achieved despite a local orientation memory that decays on the scale of about one minute. Furthermore, we find that such trajectories cannot be accounted for by simple random, isotropic models of animal locomotion. This directional behavior requires sensory neurons, but appears to be independent of known sensory signal-transduction pathways. Our results suggest that long-range directional behavior of C. elegans may not be driven by sensory cues. PMID- 24223822 TI - Mice with chimeric livers are an improved model for human lipoprotein metabolism. AB - OBJECTIVE: Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. DESIGN: FRG [ F ah(-/-) R ag2(-/-)Il2r g ( /-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. RESULTS: Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. CONCLUSION: Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism. PMID- 24223823 TI - Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells. AB - BACKGROUND AND PURPOSE: Metastatic melanoma remains one of the most invasive and highly drug resistant cancers. The over expression of anti-apoptotic protein Mcl 1 has been associated with inferior survival, poor prognosis and chemoresistance of malignant melanoma. A BH3 mimetic, ABT-737, has demonstrated efficacy in several forms of cancers. However, the efficacy of ABT-737 depends on Mcl-1. Because the over expression of Mcl-1 is frequently observed in melanoma, specifically targeting of Mcl-1 may overcome the resistance of ABT-737. In this study, we investigated the effects of Maritoclax, a novel Mcl-1-selective inhibitor, alone and in combination with ABT-737, on the survival of human melanoma cells. EXPERIMENTAL APPROACH: For cell viability assessment we performed MTT assay. Apoptosis was determined using western blot and flow cytometric analysis. KEY RESULTS: The treatment of Maritoclax reduced the cell viability of melanoma cells with an IC50 of between 2.2-5.0 uM. Further, treatment of melanoma cells with Maritoclax showed significant decrease in Mcl-1 expression. We found that Maritoclax was able to induce apoptosis in melanoma cells in a caspase dependent manner. Moreover, Maritoclax induced Mcl-1 degradation via the proteasome system, which was associated with its pro-apoptotic activity. We also found that Maritoclax treatment increased mitochondrial translocation of Bim and Bmf. Importantly, Maritoclax markedly enhanced the efficacy of ABT-737 against melanoma cells in both two- and three-dimensional spheroids. CONCLUSIONS AND IMPLICATIONS: Taken together, these results suggest that targeting of Mcl-1 by Maritoclax may represent a new therapeutic strategy for melanoma treatment that warrants further investigation as a single therapy or in combination with other agents such as Bcl-2 inhibitors. PMID- 24223824 TI - A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib. AB - PURPOSE: BIM is essential for the response to tyrosine-kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations. EXPERIMENTAL DESIGN: BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population) as a case-control study. Real-time quantitative PCR (RT qPCR) was performed to assess Bim expression in our reference population. RESULTS: No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710). A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065). T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049). Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (p<0.001) and the presence of the T allele significantly lengthened the time to achieve a major molecular response (MMR). Finally, the presence of the T allele was related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy controls. CONCLUSION: These results suggest that the analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients. PMID- 24223825 TI - Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults. AB - Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+) CD27(+) IgM(+) IgD(+)) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease. PMID- 24223827 TI - Development of a serial order in speech constrained by articulatory coordination. AB - Universal linguistic constraints seem to govern the organization of sound sequences in words. However, our understanding of the origin and development of these constraints is incomplete. One possibility is that the development of neuromuscular control of articulators acts as a constraint for the emergence of sequences in words. Repetitions of the same consonant observed in early infancy and an increase in variation of consonantal sequences over months of age have been interpreted as a consequence of the development of neuromuscular control. Yet, it is not clear how sequential coordination of articulators such as lips, tongue apex and tongue dorsum constrains sequences of labial, coronal and dorsal consonants in words over the course of development. We examined longitudinal development of consonant-vowel-consonant(-vowel) sequences produced by Japanese children between 7 and 60 months of age. The sequences were classified according to places of articulation for corresponding consonants. The analyses of individual and group data show that infants prefer repetitive and fronting articulations, as shown in previous studies. Furthermore, we reveal that serial order of different places of articulations within the same organ appears earlier and then gradually develops, whereas serial order of different articulatory organs appears later and then rapidly develops. In the same way, we also analyzed the sequences produced by English children and obtained similar developmental trends. These results suggest that the development of intra- and inter articulator coordination constrains the acquisition of serial orders in speech with the complexity that characterizes adult language. PMID- 24223826 TI - Non-genomic estrogen regulation of ion transport and airway surface liquid dynamics in cystic fibrosis bronchial epithelium. AB - Male cystic fibrosis (CF) patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL) in female CF bronchial epithelium. Here we investigated the effect of 17beta-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1) and CF (CuFi-1) bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17beta-estradiol (0.1-10 nM) reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17beta-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17beta-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17beta estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17beta-estradiol increased PKCdelta activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17beta estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17beta-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCdelta, ENaC and the Na(+)/K(+)ATPase in CF cells. PMID- 24223828 TI - Khat chewing and restrictive dietary behaviors are associated with anemia among pregnant women in high prevalence rural communities in eastern Ethiopia. AB - BACKGROUND: Anemia affects a high proportion of pregnant women in the developing countries. Factors associated with it vary in context. This study aimed to determine the prevalence and predictors of anemia among pregnant women in the rural eastern Ethiopia. METHODS: A community-based cross-sectional study was done on 1678 pregnant women who were selected by a cluster random sampling technique. A pregnant woman was identified as anemic if her hemoglobin concentration was <11 g/dl. Data were collected in a community-based setting. Multilevel mixed effect logistic regression was used to determine the adjusted odds ratios (AOR) with 95% confidence intervals (CI) for the predictors of anemia. RESULTS: Anemia was observed among 737(43.9%) of the 1678 pregnant women studied (95% CI 41.5% 46.3%). After controlling for the confounders, the risk of anemia was 29% higher in the women who chewed khat daily than those who sometimes or never did so (AOR, 1.29; 95% CI, 1.02-1.62). The study subjects with restrictive dietary behavior (reduced either meal size or frequency) had a 39% higher risk of anemia compared to those without restrictive dietary behavior (AOR, 1.39; 95% CI, 1.02-1.88). The risk of anemia was increased by 68% (AOR, 1.68; 95% CI, 1.15-2.47), and 60% (AOR, 1.60; 95% CI, 1.08-2.37) in parity levels of 2 births and 3 births, respectively. Compared to the first trimester, the risk of anemia was higher by two-fold (AOR, 2.09; 95% CI, 1.46-3.00) in the second trimester and by four-fold (AOR, 4.23; 95% CI, 2.97-6.02) in the third trimester. CONCLUSION: In this study, two out of five women were anemic. Chewing khat and restrictive dietary habits that are associated with anemia in the setting should be addressed through public education programs. Interventions should also focus on the women at higher parity levels and those who are in advanced stages of pregnancy. PMID- 24223829 TI - The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H(+)-ATPase biogenesis. AB - The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H(+)-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Delta4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. PMID- 24223830 TI - Polyphosphate-mediated inhibition of tartrate-resistant acid phosphatase and suppression of bone resorption of osteoclasts. AB - Inorganic polyphosphate (poly(P)) has recently been found to play an important role in bone formation. In this study, we found that tartrate-resistant acid phosphatase (TRAP), which is abundantly expressed in osteoclasts, has polyphosphatase activity that degrades poly(P) and yields Pi as well as shorter poly(P) chains. Since the TRAP protein that coprecipitated with anti-TRAP monoclonal antibodies exhibited both polyphosphatase and the original phosphatase activity, poly(P) degradation activity is dependent on TRAP and not on other contaminating enzymes. The ferrous chelator alpha, alpha'-bipyridyl, which inhibits the TRAP-mediated production of reactive oxygen species (ROS), had no effect on such poly(P) degradation, suggesting that the degradation is not dependent on ROS. In addition, shorter chain length poly(P) molecules were better substrates than longer chains for TRAP, and poly(P) inhibited the phosphatase activity of TRAP depending on its chain length. The IC50 of poly(P) against the original phosphatase activity of TRAP was 9.8 uM with an average chain length more than 300 phosphate residues, whereas the IC50 of poly(P) with a shorter average chain length of 15 phosphate residues was 8.3 mM. Finally, the pit formation activity of cultured rat osteoclasts differentiated by RANKL and M-CSF were markedly inhibited by poly(P), while no obvious decrease in cell number or differentiation efficiency was observed for poly(P). In particular, the inhibition of pit formation by long chain poly(P) with 300 phosphate residues was stronger than that of shorter chain poly(P). Thus, poly(P) may play an important regulatory role in osteoclastic bone resorption by inhibiting TRAP activity, which is dependent on its chain length. PMID- 24223831 TI - Distinct phyllosphere bacterial communities on Arabidopsis wax mutant leaves. AB - The phyllosphere of plants is inhabited by diverse microorganisms, however, the factors shaping their community composition are not fully elucidated. The plant cuticle represents the initial contact surface between microorganisms and the plant. We thus aimed to investigate whether mutations in the cuticular wax biosynthesis would affect the diversity of the phyllosphere microbiota. A set of four Arabidopsis thaliana eceriferum mutants (cer1, cer6, cer9, cer16) and their respective wild type (Landsberg erecta) were subjected to an outdoor growth period and analysed towards this purpose. The chemical distinctness of the mutant wax phenotypes was confirmed by gas chromatographic measurements. Next generation amplicon pyrosequencing of the bacterial communities showed distinct community patterns. This observation was supported by denaturing gradient gel electrophoresis experiments. Microbial community analyses revealed bacterial phylotypes that were ubiquitously present on all plant lines (termed "core" community) while others were positively or negatively affected by the wax mutant phenotype (termed "plant line-specific" community). We conclude from this study that plant cuticular wax composition can affect the community composition of phyllosphere bacteria. PMID- 24223832 TI - Systemic delivery of small interfering RNA targeting the interleukin-2/15 receptor beta chain prevents disease progression in experimental arthritis. AB - The role of interleukin (IL)-15 in the pathogenesis of rheumatoid arthritis (RA) is well established; however, systemic knockdown of IL-15 receptor (IL-15R) for reduction in inflammation at local sites has not been demonstrated. In this study, the therapeutic effect of intravenously administered siRNA targeting the beta chain of IL-15R which is shared by the receptor for IL-2 was examined in rats with adjuvant-induced arthritis (AA). Polyethylenimine (PEI)-complexed siRNA nanoparticles could easily accumulate in arthritic paws of AA rats. In the paws, the nanoparticles were avidly taken up by macrophages and to a lesser extent by T cells. Weekly administered IL-2/15Rbeta siRNA polyplexes were capable of decreasing disease progression in AA rats, with striking inhibition of clinical, radiologic, and histologic features of RA. The observed therapeutic effect was associated with reduced expression of proinflammatory mediators in the inflamed joints. Thus, this study provides evidence that IL-2/15Rbeta could be targeted for the treatment of RA. PMID- 24223833 TI - Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring. AB - Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p<=0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. PMID- 24223834 TI - iSubgraph: integrative genomics for subgroup discovery in hepatocellular carcinoma using graph mining and mixture models. AB - The high tumor heterogeneity makes it very challenging to identify key tumorigenic pathways as therapeutic targets. The integration of multiple omics data is a promising approach to identify driving regulatory networks in patient subgroups. Here, we propose a novel conceptual framework to discover patterns of miRNA-gene networks, observed frequently up- or down-regulated in a group of patients and to use such networks for patient stratification in hepatocellular carcinoma (HCC). We developed an integrative subgraph mining approach, called iSubgraph, and identified altered regulatory networks frequently observed in HCC patients. The miRNA and gene expression profiles were jointly analyzed in a graph structure. We defined a method to transform microarray data into graph representation that encodes miRNA and gene expression levels and the interactions between them as well. The iSubgraph algorithm was capable to detect cooperative regulation of miRNAs and genes even if it occurred only in some patients. Next, the miRNA-mRNA modules were used in an unsupervised class prediction model to discover HCC subgroups via patient clustering by mixture models. The robustness analysis of the mixture model showed that the class predictions are highly stable. Moreover, the Kaplan-Meier survival analysis revealed that the HCC subgroups identified by the algorithm have different survival characteristics. The pathway analyses of the miRNA-mRNA co-modules identified by the algorithm demonstrate key roles of Myc, E2F1, let-7, TGFB1, TNF and EGFR in HCC subgroups. Thus, our method can integrate various omics data derived from different platforms and with different dynamic scales to better define molecular tumor subtypes. iSubgraph is available as MATLAB code at http://www.cs.umd.edu/~ozdemir/isubgraph/. PMID- 24223835 TI - Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment. AB - Recent advancements in isolation techniques for cytochrome c (Cytc) have allowed us to discover post-translational modifications of this protein. We previously identified two distinct tyrosine phosphorylated residues on Cytc in mammalian liver and heart that alter its electron transfer kinetics and the ability to induce apoptosis. Here we investigated the phosphorylation status of Cytc in ischemic brain and sought to determine if insulin-induced neuroprotection and inhibition of Cytc release was associated with phosphorylation of Cytc. Using an animal model of global brain ischemia, we found a ~50% decrease in neuronal death in the CA1 hippocampal region with post-ischemic insulin administration. This insulin-mediated increase in neuronal survival was associated with inhibition of Cytc release at 24 hours of reperfusion. To investigate possible changes in the phosphorylation state of Cytc we first isolated the protein from ischemic pig brain and brain that was treated with insulin. Ischemic brains demonstrated no detectable tyrosine phosphorylation. In contrast Cytc isolated from brains treated with insulin showed robust phosphorylation of Cytc, and the phosphorylation site was unambiguously identified as Tyr97 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry. We next confirmed these results in rats by in vivo application of insulin in the absence or presence of global brain ischemia and determined that Cytc Tyr97-phosphorylation is strongly induced under both conditions but cannot be detected in untreated controls. These data suggest a mechanism whereby Cytc is targeted for phosphorylation by insulin signaling, which may prevent its release from the mitochondria and the induction of apoptosis. PMID- 24223836 TI - Sex differences in how social networks and relationship quality influence experimental pain sensitivity. AB - This is the first study to examine how both structural and functional components of individuals' social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one's significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual's social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed. PMID- 24223837 TI - Association of serum retinol binding protein 4 with atherogenic dyslipidemia in morbid obese patients. AB - Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m(2)) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9+/-14.6; 42.3+/-17.0 and 37.4+/-11.7 ug/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL. PMID- 24223838 TI - In search of epigenetic marks in testes and sperm cells of differentially fed boars. AB - In search of transmittable epigenetic marks we investigated gene expression in testes and sperm cells of differentially fed F0 boars from a three generation pig feeding experiment that showed phenotypic differences in the F2 generation. RNA samples from 8 testes of boars that received either a diet enriched in methylating micronutrients or a control diet were analyzed by microarray analysis. We found moderate differential expression between testes of differentially fed boars with a high FDR of 0.82 indicating that most of the differentially expressed genes were false positives. Nevertheless, we performed a pathway analysis and found disparate pathway maps of development_A2B receptor: action via G-protein alpha s, cell adhesion_Tight junctions and cell adhesion_Endothelial cell contacts by junctional mechanisms which show inconclusive relation to epigenetic inheritance. Four RNA samples from sperm cells of these differentially fed boars were analyzed by RNA-Seq methodology. We found no differential gene expression in sperm cells of the two groups (adjusted P-value>0.05). Nevertheless, we also explored gene expression in sperm by a pathway analysis showing that genes were enriched for the pathway maps of bacterial infections in cystic fibrosis (CF) airways, glycolysis and gluconeogenesis p.3 and cell cycle_Initiation of mitosis. Again, these pathway maps are miscellaneous without an obvious relationship to epigenetic inheritance. It is concluded that the methylating micronutrients moderately if at all affects RNA expression in testes of differentially fed boars. Furthermore, gene expression in sperm cells is not significantly affected by extensive supplementation of methylating micronutrients and thus RNA molecules could not be established as the epigenetic mark in this feeding experiment. PMID- 24223839 TI - Understanding child stunting in India: a comprehensive analysis of socio economic, nutritional and environmental determinants using additive quantile regression. AB - BACKGROUND: Most attempts to address undernutrition, responsible for one third of global child deaths, have fallen behind expectations. This suggests that the assumptions underlying current modelling and intervention practices should be revisited. OBJECTIVE: We undertook a comprehensive analysis of the determinants of child stunting in India, and explored whether the established focus on linear effects of single risks is appropriate. DESIGN: Using cross-sectional data for children aged 0-24 months from the Indian National Family Health Survey for 2005/2006, we populated an evidence-based diagram of immediate, intermediate and underlying determinants of stunting. We modelled linear, non-linear, spatial and age-varying effects of these determinants using additive quantile regression for four quantiles of the Z-score of standardized height-for-age and logistic regression for stunting and severe stunting. RESULTS: At least one variable within each of eleven groups of determinants was significantly associated with height-for-age in the 35% Z-score quantile regression. The non-modifiable risk factors child age and sex, and the protective factors household wealth, maternal education and BMI showed the largest effects. Being a twin or multiple birth was associated with dramatically decreased height-for-age. Maternal age, maternal BMI, birth order and number of antenatal visits influenced child stunting in non linear ways. Findings across the four quantile and two logistic regression models were largely comparable. CONCLUSIONS: Our analysis confirms the multifactorial nature of child stunting. It emphasizes the need to pursue a systems-based approach and to consider non-linear effects, and suggests that differential effects across the height-for-age distribution do not play a major role. PMID- 24223840 TI - Are reports of psychological stress higher in occupational studies? A systematic review across occupational and population based studies. AB - OBJECTIVES: The general health questionnaire (GHQ) is commonly used to assess symptoms of common mental disorder (CMD). Prevalence estimates for CMD caseness from UK population studies are thought to be in the range of 14-17%, and the UK occupational studies of which we are aware indicate a higher prevalence. This review will synthesise the existing research using the GHQ from both population and occupational studies and will compare the weighted prevalence estimates between them. METHODS: We conducted a systematic review and meta-analysis to examine the prevalence of CMD, as assessed by the GHQ, in all UK occupational and population studies conducted from 1990 onwards. RESULTS: The search revealed 65 occupational papers which met the search criteria and 15 relevant papers for UK population studies. The weighted prevalence estimate for CMD across all occupational studies which used the same version and cut-off for the GHQ was 29.6% (95% confidence intervals (CIs) 27.3-31.9%) and for comparable population studies was significantly lower at 19.1% (95% CIs 17.3-20.8%). This difference was reduced after restricting the studies by response rate and sampling method (23.9% (95% CIs 20.5%-27.4%) vs. 19.2% (95 CIs 17.1%-21.3%)). CONCLUSIONS: Counter intuitively, the prevalence of CMD is higher in occupational studies, compared to population studies (which include individuals not in employment), although this difference narrowed after accounting for measures of study quality, including response rate and sampling method. This finding is inconsistent with the healthy worker effect, which would presume lower levels of psychological symptoms in individuals in employment. One explanation is that the GHQ is sensitive to contextual factors, and it seems possible that symptoms of CMD are over reported when participants know that they have been recruited to a study on the basis that they belong to a specific occupational group, as in nearly all "stress" surveys. PMID- 24223841 TI - A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease. AB - Neuronal ceroid lipofuscinoses (NCLs; also known collectively as Batten Disease) are a family of autosomal recessive lysosomal storage disorders. Mutations in as many as 13 genes give rise to ~10 variants of NCL, all with overlapping clinical symptomatology including visual impairment, motor and cognitive dysfunction, seizures, and premature death. Mutations in CLN6 result in both a variant late infantile onset neuronal ceroid lipofuscinosis (vLINCL) as well as an adult-onset form of the disease called Type A Kufs. CLN6 is a non-glycosylated membrane protein of unknown function localized to the endoplasmic reticulum (ER). In this study, we perform a detailed characterization of a naturally occurring Cln6 mutant (Cln6(nclf)) mouse line to validate its utility for translational research. We demonstrate that this Cln6(nclf) mutation leads to deficits in motor coordination, vision, memory, and learning. Pathologically, we demonstrate loss of neurons within specific subregions and lamina of the cortex that correlate to behavioral phenotypes. As in other NCL models, this model displays selective loss of GABAergic interneuron sub-populations in the cortex and the hippocampus with profound, early-onset glial activation. Finally, we demonstrate a novel deficit in memory and learning, including a dramatic reduction in dendritic spine density in the cerebral cortex, which suggests a reduction in synaptic strength following disruption in CLN6. Together, these findings highlight the behavioral and pathological similarities between the Cln6(nclf) mouse model and human NCL patients, validating this model as a reliable format for screening potential therapeutics. PMID- 24223842 TI - Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ. AB - Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ. PMID- 24223843 TI - Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction. AB - The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA. PMID- 24223844 TI - MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma. AB - Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR 192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression. PMID- 24223845 TI - Metabonomics study of the therapeutic mechanism of Gynostemma pentaphyllum and atorvastatin for hyperlipidemia in rats. AB - Gynostemma pentaphyllum (GP) is widely used for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China, and atorvastatin is broadly used as an anti-hyperlipidemia drug. This research focuses on the plasma and liver metabolites in the following four groups of rats: control, a hyperlipidemia model, a hyperlipidemia model treated with GP and a hyperlipidemia model treated with atorvastatin. Using (1)H-NMR-based metabonomics, we elucidated the therapeutic mechanisms of GP and atorvastatin. Orthogonal Partial Least Squares Discriminant analysis (OPLS-DA) plotting of the metabolic state and analysis of potential biomarkers in the plasma and liver correlated well with the results of biochemical assays. GP can effectively affect lipid metabolism, and it exerts its anti-hyperlipidemia effect by elevating the level of phosphatidylcholine and decreasing the level of trimethylamine N-oxide (TMAO). In contrast, atorvastatin affects hyperlipidemia mainly during lipid metabolism and protein metabolism in vivo. PMID- 24223846 TI - Disruption of Smad4 expression in T cells leads to IgA nephropathy-like manifestations. AB - The link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been implicated, however, the mechanisms are poorly defined because of the lack of an appropriate model. Here we report a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4(co/co;Lck-cre) ). Loss of Smad4 expression in T cells results in overproduction of Th2 cytokines and high serum IgA levels. We found that Smad4(co/co;Lck-cre) mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. Furthermore, we examined the beta1, 4-galactosyltransferases (beta4GalT) enzyme which is involved in the synthesis of glycosylated murine IgA, and we found reduced beta4GalT2 and beta4GalT4 mRNA levels in B cells. These findings indicate that Smad4(co/co;Lck cre) mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and further, disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contributing to a Th2 T cell phenotype. PMID- 24223847 TI - Reduced regional homogeneity in bilateral frontostriatal system relates to higher impulsivity behavior in codeine-containing cough syrups dependent individuals. AB - BACKGROUND: In the past twenty years, codeine-containing cough syrups (CCS) was recognized as a new type of addictive drugs. However, the exact neurobiologic mechanisms underlying CCS-dependence are still ill-defined. The aims of this study are to identify CCS-related modulations of neural activity during the resting-state in CCS-dependent individuals and to investigate whether these changes of neural activity can be related to duration of CCS use, the first age of CCS use and impulse control deficits in CCS-dependent individuals. We also want to observe the impact of gray matter deficits on these functional results. METHODOLOGY/PRINCIPAL FINDINGS: Thirty CCS-dependent individuals and 30 control subjects participated. Resting-state functional MRI was performed by using gradient-echo echo-planar imaging sequence. Regional homogeneity (ReHo) was calculated by using REST software. Voxel-based analysis of the ReHo maps between controls and CCS-dependent groups was performed using two-sample t tests (p<0.05, corrected for multiple comparisons). The Barratt Impulsiveness Scale 11 (BIS.11) was surveyed to assess participants' impulsivity trait soon after MR examination. Abnormal clusters revealed by group comparison were extracted and correlated with impulsivity, duration of CCS use, and age of first CCS use. ReHo was diminished in the bilateral medial orbitofrontal cortex (mOFC) and left dorsal striatum in CCS-dependent individuals. There were negative correlations between mean ReHo in the bilateral medial OFC, left dorsal striatum and duration of CCS use, BIS.11 total scores, and the subscale of attentional impulsivity in CCS-dependent individuals. There was a significantly positive correlation between mean ReHo in the left dorsal striatum and age of first CCS use in CCS-dependent individuals. Importantly, these results still remain significant after statistically controlling for the regional gray matter deficits. CONCLUSION: Resting-state abnormalities in CCS-dependent individuals revealed in the present study may further improve our understanding about the neural substrates of impulse control dysfunction in CCS-dependent individuals. PMID- 24223848 TI - A new fungal endophyte, Scolecobasidium humicola, promotes tomato growth under organic nitrogen conditions. AB - A new fungal endophyte, Scolecobasidium humicola, was identified as a common dark septate endophytic fungal (DSE) species under both natural and agricultural conditions. This fungus was found to grow endophylically in the roots of tomato seedlings. Light microscopy of cross-sections of colonized tomato roots showed that the intercellular, pigmented hyphae of the fungus were mostly limited to the epidermal layer and formed outer mantle-like structures. Two isolates of S. humicola, H2-2 and F1-3, have shown the ability to increase plant biomass with an organic nitrogen source. This finding is the first report of S. humicola as an endophyte and could help to improve plant growth with organic nitrogen sources. PMID- 24223850 TI - Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging. AB - The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS), looking specifically at the relationship between self reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI) was used to examine where in the brain BOLD activity covaried with "state" fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI) was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS) completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a "fatigue-network" in MS. PMID- 24223849 TI - Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. AB - High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (alpha-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID- 24223851 TI - Sunny holidays before and after melanoma diagnosis are respectively associated with lower Breslow thickness and lower relapse rates in Italy. AB - BACKGROUND: Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. METHODS: A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. RESULTS: Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results. PMID- 24223852 TI - Fiber pathways of attention subnetworks revealed with tract-based spatial statistics (TBSS) and probabilistic tractography. AB - It has been widely accepted that attention can be divided into three subnetworks alerting, orienting and executive control (EC), and the subnetworks of attention are linked to distinct brain regions. However, the association between specific white matter fibers and the subnetworks of attention is not clear enough. Using diffusion tensor imaging (DTI), the white matter connectivity related to the performance of attention was assessed by attention network test (ANT) in 85 healthy adolescents. Tract-based spatial statistics (TBSS) and probabilistic diffusion tractography analysis demonstrated that cerebellothalamic tract was involved in alerting, while orienting depended upon the superior longitudinal fasciculus (SLF). In addition, EC was under the control of anterior corona radiata (ACR). Our findings suggest that different fiber pathways are involved in the three distinct subnetworks of attention. The current study will yield more precise information about the structural substrates of attention function and may aid the efforts to understand the neurophysiology of several attention disorders. PMID- 24223853 TI - Expression of a peroral infection factor determines pathogenicity and population structure in an insect virus. AB - A Nicaraguan isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus is being studied as a possible biological insecticide. This virus exists as a mixture of complete and deletion genotypes; the latter depend on the former for the production of an essential per os transmission factor (pif1) in coinfected cells. We hypothesized that the virus population was structured to account for the prevalence of pif1 defector genotypes, so that increasing the abundance of pif1 produced by a cooperator genotype in infected cells would favor an increased prevalence of the defector genotype. We tested this hypothesis using recombinant viruses with pif1 expression reprogrammed at its native locus using two exogenous promoters (egt, p10) in the pif2/pif1 intergenic region. Reprogrammed viruses killed their hosts markedly faster than the wild-type and rescue viruses, possibly due to an earlier onset of systemic infection. Group success (transmission) depended on expression of pif1, but overexpression was prejudicial to group-specific transmissibility, both in terms of reduced pathogenicity and reduced production of virus progeny from each infected insect. The presence of pif1-overproducing genotypes in the population was predicted to favor a shift in the prevalence of defector genotypes lacking pif1-expressing capabilities, to compensate for the modification in pif1 availability at the population level. As a result, defectors increased the overall pathogenicity of the virus population by diluting pif1 produced by overexpressing genotypes. These results offer a new and unexpected perspective on cooperative behavior between viral genomes in response to the abundance of an essential public good that is detrimental in excess. PMID- 24223854 TI - Grape seed proanthocyanidin extract-mediated regulation of STAT3 proteins contributes to Treg differentiation and attenuates inflammation in a murine model of obesity-associated arthritis. AB - Grape seed proanthocyanidin extract (GSPE) is a natural flavonoid that exerts anti-inflammatory properties. Obesity is an inflammatory condition and inflammatory cells and their secretion of pro-inflammatory molecules contribute to the pathogenesis of obesity. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by inflammation of joints lined by synovium. Previously, we demonstrated that obesity augmented arthritis severity in collagen induced arthritis (CIA), a murine model of human RA. Here, we investigated whether oral administration of GSPE showed antiobesity and anti-arthritic effects in high-fat diet-induced obese (DIO) mice and in obese CIA mice, respectively. The pathophysiologic mechanisms by which GSPE attenuates weight gain and arthritis severity in vivo were also investigated. In DIO mice, GSPE administration significantly inhibited weight gain, reduced fat infiltration in liver and improved serum lipid profiles. The antiobesity effect of GSPE was associated with increased populations of regulatory T (Treg) cells and those of decreased Th17 cells. Decrease of Th17 cells was associated with significant inhibition of their key transcriptional factors, pSTAT3(Tyr705) and pSTAT3(Ser727). On the contrary, GSPE-induced Treg induction was associated with enhanced pSTAT5 expression. To identify the anti-arthritis effects of GSPE, GSPE was given orally for 7 weeks after type II collagen immunization. GSPE treatment significantly attenuated the development of autoimmune arthritis in obese CIA model. In line with DIO mice, GSPE administration decreased Th17 cells and reciprocally increased Treg cells by regulating STAT proteins in autoimmune arthritis model. The expressions of pro-inflammatory cytokines and nitrotyrosine in synovium were significantly inhibited by GSPE treatment. Taken together, GSPE functions as a reciprocal regulator of T cell differentiation - suppression of Th17 cells and induction of Tregs in both DIO and obese CIA mice. GSPE may act as a therapeutic agent to treat immunologic diseases related with enhanced STAT3 activity such as metabolic disorders and autoimmune diseases. PMID- 24223855 TI - Comparison of endoscopic ultrasonography and multislice spiral computed tomography for the preoperative staging of gastric cancer - results of a single institution study of 610 Chinese patients. AB - BACKGROUND: This study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: A total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values). CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging. PMID- 24223856 TI - Traumatic brain injury precipitates cognitive impairment and extracellular Abeta aggregation in Alzheimer's disease transgenic mice. AB - Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Abeta)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Abeta deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Abeta deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Abeta deposition in the brain. PMID- 24223857 TI - Comparative and phylogenomic evidence that the alphaproteobacterium HIMB59 is not a member of the oceanic SAR11 clade. AB - SAR11 is a globally abundant group of Alphaproteobacteria in the oceans that is taxonomically not well defined. It has been suggested SAR11 should be classified into the novel order Pelagibacterales. Features such as conservation of gene content and synteny have been taken as evidence that also the divergent member HIMB59 should be included in the order. However, this proposition is controversial since phylogenetic analyses have questioned the monophyly of this grouping. Here, we performed phylogenetic analyses and reinvestigated the genomic similarity of SAR11 and HIMB59. Our phylogenetic analysis confirmed that HIMB59 is not a sister group to the other SAR11 strains. By placing the comparison in the context of the evolution of the Alphaproteobacteria, we found that none of the measures of genomic similarity supports a clustering of HIMB59 and SAR11 to the exclusion of other Alphaproteobacteria. First, pairwise sequence similarity measures for the SAR11 and HIMB59 genomes were within the range observed for unrelated pairs of Alphaproteobacteria. Second, pairwise comparisons of gene contents revealed a higher similarity of SAR11 to several other alphaproteobacterial genomes than to HIMB59. Third, the SAR11 genomes are not more similar in gene order to the HIMB59 genome than what they are to several other alphaproteobacterial genomes. Finally, in contrast to earlier reports, we observed no sequence similarity between the hypervariable region HVR2 in the SAR11 genomes and the region located at the corresponding position in the HIMB59 genome. Based on these observations, we conclude that the alphaproteobacterium HIMB59 is not monophyletic with the SAR11 strains and that genome streamlining has evolved multiple times independently in Alphaproteobacteria adapted to the upper surface waters of the oceans. PMID- 24223858 TI - The maize (Zea mays L.) AUXIN/INDOLE-3-ACETIC ACID gene family: phylogeny, synteny, and unique root-type and tissue-specific expression patterns during development. AB - The plant hormone auxin plays a key role in the coordination of many aspects of growth and development. AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes encode instable primary auxin responsive regulators of plant development that display a protein structure with four characteristic domains. In the present study, a comprehensive analysis of the 34 members of the maize Aux/IAA gene family was performed. Phylogenetic reconstructions revealed two classes of Aux/IAA proteins that can be distinguished by alterations in their domain III. Seven pairs of paralogous maize Aux/IAA proteins were discovered. Comprehensive root-type and tissue-specific expression profiling revealed unique expression patterns of the diverse members of the gene family. Remarkably, five of seven pairs of paralogous genes displayed highly correlated expression patterns in roots. All but one (ZmIAA23) tested maize Aux/IAA genes were auxin inducible, displaying two types of auxin induction within three hours of treatment. Moreover, 51 of 55 (93%) differential Aux/IAA expression patterns between different root-types followed the expression tendency: crown roots > seminal roots > primary roots > lateral roots. This pattern might imply root-type-specific regulation of Aux/IAA transcript abundance. In summary, the detailed analysis of the maize Aux/IAA gene family provides novel insights in the evolution and developmental regulation and thus the function of these genes in different root-types and tissues. PMID- 24223859 TI - Sequences of two related multiple antibiotic resistance virulence plasmids sharing a unique IS26-related molecular signature isolated from different Escherichia coli pathotypes from different hosts. AB - Enterohemorrhagic Escherichia coli (EHEC) and atypical enteropathogenic E. coli (aEPEC) are important zoonotic pathogens that increasingly are becoming resistant to multiple antibiotics. Here we describe two plasmids, pO26-CRL125 (125 kb) from a human O26:H- EHEC, and pO111-CRL115 (115kb) from a bovine O111 aEPEC, that impart resistance to ampicillin, kanamycin, neomycin, streptomycin, sulfathiazole, trimethoprim and tetracycline and both contain atypical class 1 integrons with an identical IS26-mediated deletion in their 3'-conserved segment. Complete sequence analysis showed that pO26-CRL125 and pO111-CRL115 are essentially identical except for a 9.7 kb fragment, present in the backbone of pO26-CRL125 but absent in pO111-CRL115, and several indels. The 9.7 kb fragment encodes IncI-associated genes involved in plasmid stability during conjugation, a putative transposase gene and three imperfect repeats. Contiguous sequence identical to regions within these pO26-CRL125 imperfect repeats was identified in pO111-CRL115 precisely where the 9.7 kb fragment is missing, suggesting it may be mobile. Sequences shared between the plasmids include a complete IncZ replicon, a unique toxin/antitoxin system, IncI stability and maintenance genes, a novel putative serine protease autotransporter, and an IncI1 transfer system including a unique shufflon. Both plasmids carry a derivate Tn21 transposon with an atypical class 1 integron comprising a dfrA5 gene cassette encoding resistance to trimethoprim, and 24 bp of the 3'-conserved segment followed by Tn6026, which encodes resistance to ampicillin, kanymycin, neomycin, streptomycin and sulfathiazole. The Tn21-derivative transposon is linked to a truncated Tn1721, encoding resistance to tetracycline, via a region containing the IncP-1alpha oriV. Absence of the 5 bp direct repeats flanking Tn3-family transposons, indicates that homologous recombination events played a key role in the formation of this complex antibiotic resistance gene locus. Comparative sequence analysis of these closely related plasmids reveals aspects of plasmid evolution in pathogenic E. coli from different hosts. PMID- 24223860 TI - The longitudinal association between depressive symptoms and initiation of insulin therapy in people with type 2 diabetes in primary care. AB - OBJECTIVE: To examine whether depressive symptoms are associated with time to insulin initiation in insulin-naive people with type 2 diabetes in primary care. METHODS: 1,389 participants completed the Edinburgh Depression Scale (EDS) in 2005 and were followed until: 1) insulin therapy was started, 2) death, 3) an oral antihyperglycemic drug (OAD) prescription gap >1 year, 4) last OAD prescription in 2010 or 5) the end of the study (December 31, 2010). Cox regression analyses were used to determine whether there was a difference in time to insulin initiation between people with a low versus a high depression score at baseline, adjusting for potential demographic and clinical confounders, including HbA1c levels. RESULTS: The prevalence of depression (EDS >= 12) was 12% (n=168). After a mean follow-up of 1,597 +/- 537 days, 253 (18%) participants had started insulin therapy. The rate of insulin initiation did not differ between depressed and non-depressed participants. People with depression were not more likely to start insulin therapy earlier or later than their non-depressed counterparts (HR=0.98, 95% CI 0.66-1.45), also after adjustment for sex and age (HR=0.95, 0.64 1.42). The association remained non-significant when individual candidate confounders were added to the age- and sex-adjusted base model. CONCLUSIONS: In the present study, depression was not associated with time to insulin initiation. The hypothesis that depression is associated with delayed initiation of insulin therapy merits more thorough testing, preferably in studies where more information is available about patient-, provider- and health care system factors that may influence the decision to initiate insulin. PMID- 24223862 TI - Peripapillary arterial circle of Zinn-Haller: location and spatial relationships with myopia. AB - PURPOSE: To measure histomorphometrically the location of the peripapillary arterial circle of Zinn-Haller (ZHAC) and assess its associations with axial length. METHODS: Using a light microscope, we measured the distance from the ZHAC to the peripapillary ring (optic disc border), the merging point of the dura mater with the posterior sclera ("dura-sclera point"), and the inner scleral surface. In the parapapillary region, we differentiated between beta zone (presence of Bruch's membrane, absence of retinal pigment epithelium) and gamma zone (absence of Bruch's membrane). The peripapillary scleral flange as roof of the orbital cerebrospinal fluid space was the connection between the end of the lamina cribrosa and the posterior full-thickness sclera starting at the dura sclera point. RESULTS: The study included 101 human globes (101 patients) with a mean axial length of 26.7 +/- 3.7 mm (range: 20.0-39.0 mm). The distance between the ZHAC and the peripapillary ring increased significantly with longer axial length (P<0.001; correlation coefficient r=0.49), longer parapapillary gamma zone (P<0.001;r=0.85), longer (P<0.001;r=0.73) and thinner (P<0.001;r=-0.45) peripapillary scleral flange, and thinner sclera posterior to the equator (P<0.001). ZHAC distance to the peripapillary ring was not significantly associated with length of parapapillary beta zone (P=0.33). Including only non highly myopic eyes (axial length <26.5 mm), the ZHAC distance to the disc border was not related with axial length (P=0.84). In non-highly myopic eyes, the ZHAC was located close to the dura-sclera point. With increasing axial length and decreasing thickness of the peripapillary scleral flange, the ZHAC was located closer to the inner scleral surface. CONCLUSIONS: The distance between the ZHAC and the optic disc border is markedly enlarged in highly myopic eyes. Since the ZHAC is the main arterial source for the lamina cribrosa blood supply, the finding may be of interest for the pathogenesis of the increased glaucoma susceptibility in highly myopic eyes. PMID- 24223863 TI - Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats. AB - Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life. PMID- 24223864 TI - Somatic versus dendritic resonance: differential filtering of inputs through non uniform distributions of active conductances. AB - Synaptic inputs to neurons are processed in a frequency-dependent manner, with either low-pass or resonant response characteristics. These types of filtering play a key role in the frequency-specific information flow in neuronal networks. While the generation of resonance by specific ionic conductances is well investigated, less attention has been paid to the spatial distribution of the resonance-generating conductances across a neuron. In pyramidal neurons - one of the major excitatory cell-types in the mammalian brain - a steep gradient of resonance-generating h-conductances with a 60-fold increase towards distal dendrites has been demonstrated experimentally. Because the dendritic trees of these cells are large, spatial compartmentalization of resonant properties can be expected. Here, we use mathematical descriptions of spatially extended neurons to investigate the consequences of such a distal, dendritic localization of h conductances for signal processing. While neurons with short dendrites do not exhibit a pronounced compartmentalization of resonance, i.e. the filter properties of dendrites and soma are similar, we find that neurons with longer dendrites ([Formula: see text] space constant) can show distinct filtering of dendritic and somatic inputs due to electrotonic segregation. Moreover, we show that for such neurons, experimental classification as resonant versus nonresonant can be misleading when based on somatic recordings, because for these morphologies a dendritic resonance could easily be undetectable when using somatic input. Nevertheless, noise-driven membrane-potential oscillations caused by dendritic resonance can propagate to the soma where they can be recorded, hence contrasting with the low-pass filtering at the soma. We conclude that non uniform distributions of active conductances can underlie differential filtering of synaptic input in neurons with spatially extended dendrites, like pyramidal neurons, bearing relevance for the localization-dependent targeting of synaptic input pathways to these cells. PMID- 24223865 TI - A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis. AB - BACKGROUND: Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. OBJECTIVE: To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. METHODS: One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. RESULTS: The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67-0.95) and 0.78 (CI:95%, 0.65-0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95), and for the second measurement was 0.74 (CI:95%, 0.58-0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, 3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to 1.97) respectively, in the patients studied. CONCLUSION: The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable. PMID- 24223861 TI - The diversity and distribution of fungi on residential surfaces. AB - The predominant hypothesis regarding the composition of microbial assemblages in indoor environments is that fungal assemblages are structured by outdoor air with a moderate contribution by surface growth, whereas indoor bacterial assemblages represent a mixture of bacteria entered from outdoor air, shed by building inhabitants, and grown on surfaces. To test the fungal aspect of this hypothesis, we sampled fungi from three surface types likely to support growth and therefore possible contributors of fungi to indoor air: drains in kitchens and bathrooms, sills beneath condensation-prone windows, and skin of human inhabitants. Sampling was done in replicated units of a university-housing complex without reported mold problems, and sequences were analyzed using both QIIME and the new UPARSE approach to OTU-binning, to the same result. Surfaces demonstrated a mycological profile similar to that of outdoor air from the same locality, and assemblages clustered by surface type. "Weedy" genera typical of indoor air, such as Cladosporium and Cryptococcus, were abundant on sills, as were a diverse set of fungi of likely outdoor origin. Drains supported more depauperate assemblages than the other surfaces and contained thermotolerant genera such as Exophiala, Candida, and Fusarium. Most surprising was the composition detected on residents' foreheads. In addition to harboring Malassezia, a known human commensal, skin also possessed a surprising richness of non-resident fungi, including plant pathogens such as ergot (Claviceps purperea). Overall, fungal richness across indoor surfaces was high, but based on known autecologies, most of these fungi were unlikely to be growing on surfaces. We conclude that while some endogenous fungal growth on typical household surfaces does occur, particularly on drains and skin, all residential surfaces appear - to varying degrees - to be passive collectors of airborne fungi of putative outdoor origin, a view of the origins of the indoor microbiome quite different from bacteria. PMID- 24223866 TI - Intravenous iron supplementation practices and short-term risk of cardiovascular events in hemodialysis patients. AB - BACKGROUND & OBJECTIVES: Intravenous iron supplementation is widespread in the hemodialysis population, but there is uncertainty about the safest dosing strategy. We compared the safety of different intravenous iron dosing practices on the risk of adverse cardiovascular outcomes in a large population of hemodialysis patients. DESIGN SETTINGS PARTICIPANTS & MEASUREMENTS: A retrospective cohort was created from the clinical database of a large dialysis provider (years 2004-2008) merged with administrative data from the United States Renal Data System. Dosing comparisons were (1) bolus (consecutive doses >= 100 mg exceeding 600 mg during one month) versus maintenance (all other iron doses during the month); and (2) high (> 200 mg over 1 month) versus low dose (<= 200 mg over 1 month). We established a 6-month baseline period (to identify potential confounders and effect modifiers), a one-month iron exposure period, and a three month follow-up period. Outcomes were myocardial infarction, stroke, and death from cardiovascular disease. RESULTS: 117,050 patients contributed 776,203 unique iron exposure/follow-up periods. After adjustment, we found no significant associations of bolus dose versus maintenance, hazards ratio for composite outcome, 1.03 (95% C.I. 0.99, 1.07), or high dose versus low dose intravenous iron, hazards ratio for composite outcome, 0.99 (95% C.I. 0.96, 1.03). There were no consistent associations of either high or bolus dose versus low or maintenance respectively among pre-specified subgroups. CONCLUSIONS: Strategies favoring large doses of intravenous iron were not associated with increased short-term cardiovascular morbidity and mortality. Investigation of the long-term safety of the various intravenous iron supplementation strategies may still be warranted. PMID- 24223867 TI - Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF) beta2 and migration of glioma cells in vitro. AB - BACKGROUND: An important phenomenon observed in glioma metabolism is increased aerobic glycolysis in tumor cells, which is generally referred to as the Warburg effect. Transforming growth factor (TGF)-beta2, which we previously showed to be induced by lactic acid, is a key pathophysiological factor in glioblastoma, leading to increased invasion and severe local immunosuppression after proteolytic cleavage from its latency associated peptide. In this study we tested the hypothesis, that lactate regulates TGF-beta2 expression and glioma cell migration via induction of Thrombospondin-1 (THBS-1), a TGF-beta activating protein. METHODS: Lactate levels were reduced by knockdown of LDH-A using specific small interfering RNA (siRNA) and competitive inhibition of LDH-A by sodium oxamate. Knockdown of THBS-1 was performed using specific siRNA. Western Blot, qRT-PCR, and ELISA were used to investigate expression levels of LDH-A, LDH B, TGF-beta2 and THBS-1. Migration of cells was examined by Spheroid, Scratch and Boyden Chamber assays. RESULTS: Knockdown of LDH-A with subsequent decrease of lactate concentration leads to reduced levels of THBS-1 and TGF-beta2 in glioma cells. Lactate addition increases THBS-1 protein, leading to increased activation of TGF-beta2. Inhibition of THBS-1 reduces TGF-beta2 protein and migration of glioma cells. Addition of synthetic THBS-1 can rescue reduced TGF-beta2 protein levels and glioma cell migration in siLDH-A treated cells. CONCLUSION: We define a regulatory cascade between lactate, THBS-1 and TGF-beta2, leading to enhanced migration of glioma cells. Our results demonstrate a specific interaction between tumor metabolism and migration and provide a better understanding of the mechanisms underlying glioma cell invasion. PMID- 24223868 TI - A comparative study between use of arthroscopic lavage and arthrocentesis of temporomandibular joint based on computational fluid dynamics analysis. AB - Arthroscopic lavage and arthrocentesis, performed with different inner-diameter lavage needles, are the current minimally invasive techniques used in temporomandibular joint disc displacement (TMJ-DD) for pain reduction and functional improvement. In the current study, we aimed to explore the biomechanical influence and explain the diverse clinical outcomes of these two approaches with computational fluid dynamics. Data was retrospectively analyzed from 78 cases that had undergone arthroscopic lavage or arthrocentesis for TMJ-DD from 2002 to 2010. Four types of finite volume models, featuring irrigation needles of different diameters, were constructed based on computed tomography images. We investigated the flow pattern and pressure distribution of lavage fluid secondary to caliber-varying needles. Our results demonstrated that the size of outflow portal was the critical factor in determining irrigated flow rate, with a larger inflow portal and a smaller outflow portal leading to higher intra-articular pressure. This was consistent with clinical data suggesting that increasing the mouth opening and maximal contra-lateral movement led to better outcomes following arthroscopic lavage. The findings of this study could be useful for choosing the lavage apparatus according to the main complaint of pain, or limited mouth opening, and examination of joint movements. PMID- 24223869 TI - Reorienting in virtual 3D environments: do adult humans use principal axes, medial axes or local geometry? AB - Studies have shown that animals, including humans, use the geometric properties of environments to orient. It has been proposed that orientation is accomplished primarily by encoding the principal axes (i.e., global geometry) of an environment. However, recent research has shown that animals use local information such as wall length and corner angles as well as local shape parameters (i.e., medial axes) to orient. The goal of the current study was to determine whether adult humans reorient according to global geometry based on principal axes or whether reliance is on local geometry such as wall length and sense information or medial axes. Using a virtual environment task, participants were trained to select a response box located at one of two geometrically identical corners within a featureless rectangular-shaped environment. Participants were subsequently tested in a transformed L-shaped environment that allowed for a dissociation of strategies based on principal axes, medial axes and local geometry. Results showed that participants relied primarily on a medial axes strategy to reorient in the L-shaped test environment. Importantly, the search behaviour of participants could not be explained by a principal axes-based strategy. PMID- 24223870 TI - Incorporating conservation zone effectiveness for protecting biodiversity in marine planning. AB - Establishing different types of conservation zones is becoming commonplace. However, spatial prioritization methods that can accommodate multiple zones are poorly understood in theory and application. It is typically assumed that management regulations across zones have differential levels of effectiveness ("zone effectiveness") for biodiversity protection, but the influence of zone effectiveness on achieving conservation targets has not yet been explored. Here, we consider the zone effectiveness of three zones: permanent closure, partial protection, and open, for planning for the protection of five different marine habitats in the Vatu-i-Ra Seascape, Fiji. We explore the impact of differential zone effectiveness on the location and costs of conservation priorities. We assume that permanent closure zones are fully effective at protecting all habitats, open zones do not contribute towards the conservation targets and partial protection zones lie between these two extremes. We use four different estimates for zone effectiveness and three different estimates for zone cost of the partial protection zone. To enhance the practical utility of the approach, we also explore how much of each traditional fishing ground can remain open for fishing while still achieving conservation targets. Our results show that all of the high priority areas for permanent closure zones would not be a high priority when the zone effectiveness of the partial protection zone is equal to that of permanent closure zones. When differential zone effectiveness and costs are considered, the resulting marine protected area network consequently increases in size, with more area allocated to permanent closure zones to meet conservation targets. By distributing the loss of fishing opportunity equitably among local communities, we find that 84-88% of each traditional fishing ground can be left open while still meeting conservation targets. Finally, we summarize the steps for developing marine zoning that accounts for zone effectiveness. PMID- 24223871 TI - Dietary adequacy of vitamin D and calcium among Inuit and Inuvialuit women of child-bearing age in Arctic Canada: a growing concern. AB - BACKGROUND: Arctic populations are at an increased risk of vitamin D inadequacy due to geographic latitude and a nutrition transition. This study aimed to assess the adequacy of dietary vitamin D and calcium among women of child-bearing age in Arctic Canada. METHODS: This study collected data from 203 randomly selected women of child-bearing age (19-44 years) in Nunavut and the Northwest Territories of Arctic Canada. Cross-sectional surveys using a validated quantitative food frequency questionnaire were analysed to determine the dietary adequacy of vitamin D and calcium and summarize the top foods contributing to vitamin D and calcium intake among traditional food eaters (TFE) and non-traditional food eaters (NTFE). RESULTS: The response rate was between 69-93% depending on the community sampled. Mean BMIs for both TFE and NTFE were above the normal range. Traditional food eaters had a significantly higher median vitamin D intake compared with non-traditional eaters (TFE=5.13 +/- 5.34 ug/day; NTFE=3.5 +/- 3.22 ug/day, p=0.004). The majority of women (87%) were below the Estimated Average Requirements (EAR) for vitamin D. Despite adequate median daily calcium intake in both TFE (1,299 +/- 798 mg/day) and NTFE (992 +/- 704 mg/day; p=0.0005), 27% of the study population fell below the EAR for calcium. Dairy products contributed the most to intake of vitamin D (TFE=30.7%; NTFE=39.1%) and calcium (TFE=25.5%; NTFE=34.5%). CONCLUSIONS: Inadequate dietary vitamin D intake is evident among Inuit and Inuvialuit women of child-bearing age in Arctic Canada. Promotion of nutrient-rich sources of traditional foods, supplementation protocols and/or expanded food fortification should be considered to address this nutrition concern. PMID- 24223872 TI - Detection of salt marsh vegetation stress and recovery after the Deepwater Horizon Oil Spill in Barataria Bay, Gulf of Mexico using AVIRIS data. AB - The British Petroleum Deepwater Horizon Oil Spill in the Gulf of Mexico was the biggest oil spill in US history. To assess the impact of the oil spill on the saltmarsh plant community, we examined Advanced Visible Infrared Imaging Spectrometer (AVIRIS) data flown over Barataria Bay, Louisiana in September 2010 and August 2011. Oil contamination was mapped using oil absorption features in pixel spectra and used to examine impact of oil along the oiled shorelines. Results showed that vegetation stress was restricted to the tidal zone extending 14 m inland from the shoreline in September 2010. Four indexes of plant stress and three indexes of canopy water content all consistently showed that stress was highest in pixels next to the shoreline and decreased with increasing distance from the shoreline. Index values along the oiled shoreline were significantly lower than those along the oil-free shoreline. Regression of index values with respect to distance from oil showed that in 2011, index values were no longer correlated with proximity to oil suggesting that the marsh was on its way to recovery. Change detection between the two dates showed that areas denuded of vegetation after the oil impact experienced varying degrees of re-vegetation in the following year. This recovery was poorest in the first three pixels adjacent to the shoreline. This study illustrates the usefulness of high spatial resolution airborne imaging spectroscopy to map actual locations where oil from the spill reached the shore and then to assess its impacts on the plant community. We demonstrate that post-oiling trends in terms of plant health and mortality could be detected and monitored, including recovery of these saltmarsh meadows one year after the oil spill. PMID- 24223873 TI - Validation of 'variable number of tandem repeat'-based approach for examination of 'Candidatus Liberibacter asiaticus' diversity and its applications for the analysis of the pathogen populations in the areas of recent introduction. AB - Citrus greening (Huanglongbing, HLB) is one of the most destructive diseases of citrus worldwide. In South Asia HLB has been known for more than a century, while in Americas the disease was found relatively recently. HLB is associated with three species of 'Candidatus Liberibacter' among which 'Ca. Liberibacter asiaticus' (CLas) has most wide distribution. Recently, a number of studies identified different regions in the CLas genome with variable number of tandem repeats (VNTRs) that could be used for examination of CLas diversity. One of the objectives of the work presented here was to further validate the VNTR analysis based approach by assessing the stability of these repeats upon multiplication of the pathogen in a host over an extended period of time and upon its passaging from a host to a host using CLas populations from Florida. Our results showed that the numbers of tandem repeats in the four loci tested display very distinguishable "signature profiles" for the two Florida-type CLas haplotype groups. Remarkably, the profiles do not change upon passage of the pathogen in citrus and psyllid hosts as well as after its presence within a host over a period of five years, suggesting that VNTR analysis-based approach represents a valid methodology for examination of the pathogen populations in various geographical regions. Interestingly, an extended analysis of CLas populations in different locations throughout Florida and in several countries in the Caribbean and Central America regions and in Mexico where the pathogen has been introduced recently demonstrated the dispersion of the same haplotypes of CLas. On the other hand, these CLas populations appeared to differ significantly from those obtained from locations where the disease has been present for a much longer time. PMID- 24223874 TI - CDK-dependent nuclear localization of B-cyclin Clb1 promotes FEAR activation during meiosis I in budding yeast. AB - Cyclin-dependent kinases (CDK) are master regulators of the cell cycle in eukaryotes. CDK activity is regulated by the presence, post-translational modification and spatial localization of its regulatory subunit cyclin. In budding yeast, the B-cyclin Clb1 is phosphorylated and localizes to the nucleus during meiosis I. However the functional significance of Clb1's phosphorylation and nuclear localization and their mutual dependency is unknown. In this paper, we demonstrate that meiosis-specific phosphorylation of Clb1 requires its import to the nucleus but not vice versa. While Clb1 phosphorylation is dependent on activity of both CDK and polo-like kinase Cdc5, its nuclear localization requires CDK but not Cdc5 activity. Furthermore we show that increased nuclear localization of Clb1 during meiosis enhances activation of FEAR (Cdc Fourteen Early Anaphase Release) pathway. We discuss the significance of our results in relation to regulation of exit from meiosis I. PMID- 24223875 TI - A set of engineered Escherichia coli expression strains for selective isotope and reactivity labeling of amino acid side chains and flavin cofactors. AB - Biological reactions are facilitated by delicate molecular interactions between proteins, cofactors and substrates. To study and understand their dynamic interactions researchers have to take great care not to influence or distort the object of study. As a non-invasive alternative to a site-directed mutagenesis approach, selective isotope labeling in combination with vibrational spectroscopy may be employed to directly identify structural transitions in wild type proteins. Here we present a set of customized Escherichia coli expression strains, suitable for replacing both the flavin cofactor and/or selective amino acids with isotope enriched or chemically modified substrates. For flavin labeling we report optimized auxotrophic strains with significantly enhanced flavin uptake properties. Labeled protein biosynthesis using these strains was achieved in optimized cultivation procedures using high cell density fermentation. Finally, we demonstrate how this approach is used for a clear assignment of vibrational spectroscopic difference signals of apoprotein and cofactor of a flavin containing photoreceptor of the BLUF (Blue Light receptors Using FAD) family. PMID- 24223876 TI - Task-related changes in functional properties of the human brain network underlying attentional control. AB - Previous studies have demonstrated task-related changes in brain activation and inter-regional connectivity but the temporal dynamics of functional properties of the brain during task execution is still unclear. In the present study, we investigated task-related changes in functional properties of the human brain network by applying graph-theoretical analysis to magnetoencephalography (MEG). Subjects performed a cue-target attention task in which a visual cue informed them of the direction of focus for incoming auditory or tactile target stimuli, but not the sensory modality. We analyzed the MEG signal in the cue-target interval to examine network properties during attentional control. Cluster-based non-parametric permutation tests with the Monte-Carlo method showed that in the cue-target interval, beta activity was desynchronized in the sensori-motor region including premotor and posterior parietal regions in the hemisphere contralateral to the attended side. Graph-theoretical analysis revealed that, in beta frequency, global hubs were found around the sensori-motor and prefrontal regions, and functional segregation over the entire network was decreased during attentional control compared to the baseline. Thus, network measures revealed task-related temporal changes in functional properties of the human brain network, leading to the understanding of how the brain dynamically responds to task execution as a network. PMID- 24223877 TI - The risk of schizophrenia and child psychiatric disorders in offspring of mothers with lung cancer and other types of cancer: a Danish nationwide register study. AB - BACKGROUND: Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements. METHODS: Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk. RESULTS: In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types. CONCLUSIONS: In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking. PMID- 24223878 TI - Development of a brief instrument for assessing healthcare employee satisfaction in a low-income setting. AB - BACKGROUND: Ethiopia is one of 57 countries identified by the World Health Report 2006 as having a severely limited number of health care professionals. In recognition of this shortage, the Ethiopian Federal Ministry of Health, through the Ethiopian Hospital Management Initiative, prioritized the need to improve retention of health care workers. Accordingly, we sought to develop the Satisfaction of Employees in Health Care (SEHC) survey for use in hospitals and health centers throughout Ethiopia. METHODS: Literature reviews and cognitive interviews were used to generate a staff satisfaction survey for use in the Ethiopian healthcare setting. We pretested the survey in each of the six hospitals and four health centers across Ethiopia (98% response rate). We assessed content validity and convergent validity using factor analysis and examined reliability using the Cronbach alpha coefficients to assess internal consistency. The final survey was comprised of 18 questions about specific aspects of an individual's work and two overall staff satisfaction questions. RESULTS: We found support for content validity, as data from the 18 responses factored into three factors, which we characterized as 1) relationship with management and supervisors, 2) job content, and 3) relationships with coworkers. Summary scores for two factors (relationship with management and supervisors and job content) were significantly associated (P-value, <0.001) with the two overall satisfaction items. Cronbach's alpha coefficients showed good to excellent internal consistency (Cronbach alpha coefficients >0.70) for the items in the three summary scores. CONCLUSIONS: The introduction of consistent and reliable measures of staff satisfaction is crucial to understand and improve employee retention rates, which threaten the successful achievement of the Millennium Development Goals in low-income countries. The use of the SEHC survey in Ethiopian healthcare facilities has ample leadership support, which is essential for addressing problems that reduce staff satisfaction and exacerbate excessive workforce shortages. PMID- 24223879 TI - A functional variant rs1820453 in YAP1 and breast cancer risk in Chinese population. AB - BACKGROUND: To investigate the association between rs1820453 which located in the promoter region of yes-associated protein 1 (YAP1) gene and breast cancer (BC) risk. METHOD AND FINDINGS: We conducted a hospital-based case-control study including a total of 480 BC cases and 545 cancer-free controls in Chinese population. Then the expression quantitative trait locus (e-QTL) analysis was performed to explore the possible function of rs1820453 to the YAP1 gene expression. The association between rs1820453 and BC risk was significantly identified with the odds ratio (OR) was 1.27 (95 % confidence interval (CI) =1.03 1.57) under allelic model when adjusted by age and menopausal status. In addition, the correlation analysis of rs1820453 and YAP1 expression level found that this variant was significantly associated with the gene expression in Chinese population. When compared with level of mRNA expression of the AA genotype (6.011 +/- 0.046), the mRNA expression level in CC genotype (5.903 +/- 0.026) was statistically lower (P=0.024). CONCLUSION: The results from this study suggested that rs1820453 A>C change may affect the gene expression and contribute to the risk of developing BC in Chinese population though larger sample-size studies along with functional experiments were anticipated to warrant the results. PMID- 24223881 TI - Enhancing the function of CD34(+) cells by targeting plasminogen activator inhibitor-1. AB - Previously, we showed that transient inhibition of TGF- beta1 resulted in correction of key aspects of diabetes-induced CD34(+) cell dysfunction. In this report, we examine the effect of transient inhibition of plasminogen activator inhibitor-1 (PAI-1), a major gene target of TGF-beta1 activation. Using gene array studies, we examined CD34(+) cells isolated from a cohort of longstanding diabetic individuals, free of microvascular complications despite suboptimal glycemic control, and found that the cells exhibited reduced transcripts of both TGF-beta1 and PAI-1 compared to age, sex, and degree of glycemic control-matched diabetic individuals with microvascular complications. CD34(+) cells from diabetic subjects with microvascular complications consistently exhibited higher PAI-1 mRNA than age-matched non-diabetic controls. TGF- beta1 phosphorodiamidate morpholino oligo (PMO) reduced PAI-1 mRNA in diabetic (p<0.01) and non-diabetic (p=0.05) CD34(+) cells. To reduce PAI-1 in human CD34(+) cells, we utilized PAI-1 siRNA, lentivirus expressing PAI-1 shRNA or PAI-1 PMO. We found that inhibition of PAI-1 promoted CD34(+) cell proliferation and migration in vitro, likely through increased PI3(K) activity and increased cGMP production. Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+) cells to injured acellular retinal capillaries was greater after PAI-1-PMO treatment compared with control PMO-treated cells. Targeting PAI-1 offers a promising therapeutic strategy for restoring vascular reparative function in defective diabetic progenitors. PMID- 24223882 TI - Congenital cerebral palsy, child sex and parent cardiovascular risk. AB - OBJECTIVE: Genes associated with cardiovascular disease may also be risk factors for congenital cerebral palsy (CP) and these associations may be modified by sex, since there is an increased risk of CP in male children. We investigated the association between CP of the child with cardiovascular disease in parents, taking sex of the child into consideration. METHODS: All parents of non-adopted singletons born in Denmark between 1973 and 2003 were included. Parents of a child with CP, confirmed by the Danish National CP registry, were considered exposed. Cox proportional hazards regressions were used to model risk of cardiovascular outcomes for exposed parents compared to all other parents beginning at the child's 10(th) birthday. RESULTS: We identified 733,730 mothers and 666,652 fathers among whom 1,592 and 1,484, respectively, had a child with CP. The mean age for mothers at end of follow up was 50 +/- 8 years. After adjustment for maternal age, parental education, child's sex, child's residence, child being small for gestational age and maternal hypertensive disorder during pregnancy, mothers of CP male children had an excess risk of cardiovascular disease (HR: 1.52, 95% CI: 1.16-2.00), attributable mostly to an increased incidence of hypertension and cerebrovascular disease. After additional adjustment for preterm birth, the association was markedly attenuated for cardiovascular disease (1.34, 95%CI: 1.02 - 1.76), became nonsignificant for hypertension, but remained significant for cerebrovascular disease (HR: 2.73, 95% CI: 1.45- 5.12). There was no increased risk of cardiovascular events in mothers of female CP children, or fathers of CP children of any sex. CONCLUSIONS: Women that have a male child with CP are at increased risk for premature cardiovascular disease. Part of this association may be related to risk factors for preterm births. PMID- 24223880 TI - Brood ball-mediated transmission of microbiome members in the dung beetle, Onthophagus taurus (Coleoptera: Scarabaeidae). AB - Insects feeding on plant sap, blood, and other nutritionally incomplete diets are typically associated with mutualistic bacteria that supplement missing nutrients. Herbivorous mammal dung contains more than 86% cellulose and lacks amino acids essential for insect development and reproduction. Yet one of the most ecologically necessary and evolutionarily successful groups of beetles, the dung beetles (Scarabaeinae) feeds primarily, or exclusively, on dung. These associations suggest that dung beetles may benefit from mutualistic bacteria that provide nutrients missing from dung. The nesting behaviors of the female parent and the feeding behaviors of the larvae suggest that a microbiome could be vertically transmitted from the parental female to her offspring through the brood ball. Using sterile rearing and a combination of molecular and culture based techniques, we examine transmission of the microbiome in the bull-headed dung beetle, Onthophagus taurus. Beetles were reared on autoclaved dung and the microbiome was characterized across development. A ~1425 bp region of the 16S rRNA identified Pseudomonadaceae, Enterobacteriaceae, and Comamonadaceae as the most common bacterial families across all life stages and populations, including cultured isolates from the 3(rd) instar digestive system. Finer level phylotyping analyses based on lepA and gyrB amplicons of cultured isolates placed the isolates closest to Enterobacter cloacae, Providencia stuartii, Pusillimonas sp., Pedobacter heparinus, and Lysinibacillus sphaericus. Scanning electron micrographs of brood balls constructed from sterile dung reveals secretions and microbes only in the chamber the female prepares for the egg. The use of autoclaved dung for rearing, the presence of microbes in the brood ball and offspring, and identical 16S rRNA sequences in both parent and offspring suggests that the O. taurus female parent transmits specific microbiome members to her offspring through the brood chamber. The transmission of the dung beetle microbiome highlights the maintenance and likely importance of this newly characterized bacterial community. PMID- 24223883 TI - Alterations in the cell cycle in the cerebellum of hyperbilirubinemic Gunn rat: a possible link with apoptosis? AB - Severe hyperbilirubinemia causes neurological damage both in humans and rodents. The hyperbilirubinemic Gunn rat shows a marked cerebellar hypoplasia. More recently bilirubin ability to arrest the cell cycle progression in vascular smooth muscle, tumour cells, and, more importantly, cultured neurons has been demonstrated. However, the involvement of cell cycle perturbation in the development of cerebellar hypoplasia was never investigated before. We explored the effect of sustained spontaneous hyperbilirubinemia on cell cycle progression and apoptosis in whole cerebella dissected from 9 day old Gunn rat by Real Time PCR, Western blot and FACS analysis. The cerebellum of the hyperbilirubinemic Gunn rats exhibits an increased cell cycle arrest in the late G0/G1 phase (p < 0.001), characterized by a decrease in the protein expression of cyclin D1 (15%, p < 0.05), cyclin A/A1 (20 and 30%, p < 0.05 and 0.01, respectively) and cyclin dependent kinases2 (25%, p < 0.001). This was associated with a marked increase in the 18 kDa fragment of cyclin E (67%, p < 0.001) which amplifies the apoptotic pathway. In line with this was the increase of the cleaved form of Poly (ADP ribose) polymerase (54%, p < 0.01) and active Caspase3 (two fold, p < 0.01). These data indicate that the characteristic cerebellar alteration in this developing brain structure of the hyperbilirubinemic Gunn rat may be partly due to cell cycle perturbation and apoptosis related to the high bilirubin concentration in cerebellar tissue mainly affecting granular cells. These two phenomena might be intimately connected. PMID- 24223884 TI - An optimized immunohistochemistry technique improves NMO-IgG detection: study comparison with cell-based assays. AB - Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection. PMID- 24223885 TI - Genetic variation of drought tolerance in Pinus pinaster at three hierarchical levels: a comparison of induced osmotic stress and field testing. AB - Understanding the survival capacity of forest trees to periods of severe water stress could improve knowledge of the adaptive potential of different species under future climatic scenarios. In long lived organisms, like forest trees, the combination of induced osmotic stress treatments and field testing can elucidate the role of drought tolerance during the early stages of establishment, the most critical in the life of the species. We performed a Polyethylene glycol-osmotic induced stress experiment and evaluated two common garden experiments (xeric and mesic sites) to test for survival and growth of a wide range clonal collection of Maritime pine. This study demonstrates the importance of additive vs non additive effects for drought tolerance traits in Pinus pinaster, and shows differences in parameters determining the adaptive trajectories of populations and family and clones within populations. The results show that osmotic adjustment plays an important role in population variation, while biomass allocation and hydric content greatly influence survival at population level. Survival in the induced osmotic stress experiment presented significant correlations with survival in the xeric site, and height growth at the mesic site, at population level, indicating constraints of adaptation for those traits, while at the within population level no significant correlation existed. These results demonstrate that population differentiation and within population genetic variation for drought tolerance follow different patterns. PMID- 24223887 TI - Multiple chronic health conditions and their link with labour force participation and economic status. AB - AIMS: To assess the labour force participation and quantify the economic status of older Australian workers with multiple health conditions. BACKGROUND: Many older people suffer from multiple health conditions. While multiple morbidities have been highlighted as an important research topic, there has been limited research in this area to date, particularly on the economic status of those with multiple morbidities. METHODS: Cross sectional analysis of Health&WealthMOD, a microsimulation model of Australians aged 45 to 64 years. RESULTS: People with one chronic health condition had 0.59 times the odds of being employed compared to those with no condition (OR 0.59, 95% CI: 0.49, 0.71), and those with four or more conditions had 0.14 times the odds of being employed compared to those with no condition (OR 0.14, 95% CI: 0.11, 0.18). People with one condition received a weekly income 32% lower than those with no health condition, paid 49 % less tax, and received 37% more in government transfer payments; those with four or more conditions received a weekly income 94% lower, paid 97% less in tax and received over 2,000% more in government transfer payments per week than those with no condition. CONCLUSION: While having a chronic health condition is associated with lower labour force participation and poorer economic status, having multiple conditions compounds the affect - with these people being far less likely to be employed and having drastically lower incomes. PMID- 24223886 TI - Recycling of the high valence States of heme proteins by cysteine residues of THIMET-oligopeptidase. AB - The peptidolytic enzyme THIMET-oligopeptidase (TOP) is able to act as a reducing agent in the peroxidase cycle of myoglobin (Mb) and horseradish peroxidase (HRP). The TOP-promoted recycling of the high valence states of the peroxidases to the respective resting form was accompanied by a significant decrease in the thiol content of the peptidolytic enzyme. EPR (electron paramagnetic resonance) analysis using DBNBS spin trapping revealed that TOP also prevented the formation of tryptophanyl radical in Mb challenged by H2O2. The oxidation of TOP thiol groups by peroxidases did not promote the inactivating oligomerization observed in the oxidation promoted by the enzyme aging. These findings are discussed towards a possible occurrence of these reactions in cells. PMID- 24223888 TI - Long-term phenological shifts in raptor migration and climate. AB - Climate change is having a discernible effect on many biological and ecological processes. Among observed changes, modifications in bird phenology have been widely documented. However, most studies have interpreted phenological shifts as gradual biological adjustments in response to the alteration of the thermal regime. Here we analysed a long-term dataset (1980-2010) of short-distance migratory raptors in five European regions. We revealed that the responses of these birds to climate-induced changes in autumn temperatures are abrupt and synchronous at a continental scale. We found that when the temperatures increased, birds delayed their mean passage date of autumn migration. Such delay, in addition to an earlier spring migration, suggests that a significant warming may induce an extension of the breeding-area residence time of migratory raptors, which may eventually lead to residency. PMID- 24223889 TI - Recurrence of preeclampsia in northern Tanzania: a registry-based cohort study. AB - OBJECTIVE: Preeclampsia occurs in about 4 per cent of pregnancies worldwide, and may have particularly serious consequences for women in Africa. Studies in western countries have shown that women with preeclampsia in one pregnancy have a substantially increased risk of preeclampsia in subsequent pregnancies. We estimate the recurrence risks of preeclampsia in data from Northern Tanzania. METHODS: A prospective cohort study was designed using 19,811 women who delivered singleton infants at a hospital in Northern Tanzania between 2000 and 2008. A total of 3,909 women were recorded with subsequent deliveries in the hospital with follow up through 2010. Adjusted recurrence risks of preeclampsia were computed using regression models. RESULTS: The absolute recurrence risk of preeclampsia was 25%, which was 9.2-fold (95% CI: 6.4 - 13.2) compared with the risk for women without prior preeclampsia. When there were signs that the preeclampsia in a previous pregnancy had been serious either because the baby was delivered preterm or had died in the perinatal period, the recurrence risk of preeclampsia was even higher. Women who had preeclampsia had increased risk of a series of adverse pregnancy outcomes in future pregnancies. These include perinatal death (RR= 4.3), a baby with low birth weight (RR= 3.5), or a preterm birth (RR= 2.5). These risks were only partly explained by recurrence of preeclampsia. CONCLUSIONS: Preeclampsia in one pregnancy is a strong predictor for preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies in Tanzania. Women with previous preeclampsia may benefit from close follow-up during their pregnancies. PMID- 24223890 TI - Bacterial viability and physical properties of antibacterially modified experimental dental resin composites. AB - PURPOSE: To investigate the antibacterial effect and the effect on the material properties of a novel delivery system with Irgasan as active agent and methacrylated polymerizable Irgasan when added to experimental dental resin composites. MATERIALS AND METHODS: A delivery system based on novel polymeric hollow beads, loaded with Irgasan and methacrylated polymerizable Irgasan as active agents were used to manufacture three commonly formulated experimental resin composites. The non-modified resin was used as standard (ST). Material A contained the delivery system providing 4 % (m/m) Irgasan, material B contained 4 % (m/m) methacrylated Irgasan and material C 8 % (m/m) methacrylated Irgasan. Flexural strength (FS), flexural modulus (FM), water sorption (WS), solubility (SL), surface roughness Ra, polymerization shrinkage, contact angle Theta, total surface free energy gammaS and its apolar gammaS (LW), polar gammaS (AB), Lewis acid gammaS (+)and base gammaS (-) term as well as bacterial viability were determined. Significance was p < 0.05. RESULTS: The materials A to C were not unacceptably influenced by the modifications and achieved the minimum values for FS, WS and SL as requested by EN ISO 4049 and did not differ from ST what was also found for Ra. Only A had lower FM than ST. Theta of A and C was higher and gammaS (AB) of A and B was lower than of ST. Materials A to C had higher gammaS (+) than ST. The antibacterial effect of materials A to C was significantly increased when compared with ST meaning that significantly less vital cells were found. CONCLUSION: Dental resin composites with small quantities of a novel antibacterially doped delivery system or with an antibacterial monomer provided acceptable physical properties and good antibacterial effectiveness. The sorption material being part of the delivery system can be used as a vehicle for any other active agent. PMID- 24223891 TI - Successional distance between the source and recipient influence seed germination and seedling survival during surface soil replacement in SW China. AB - Adding propagules (source) to a degraded site (recipient) is a common way of manipulating secondary succession to restore diversity and services formerly provided by forests. However, heretofore no study has considered the effect of "successional distance" between source and recipient site. Four sites in the Shilin karst area of SW China were treated as different states along a secondary successional sere: grass, shrub, young secondary forest, and primary forest. Ten 1 m *1m soil quadrats in the grass, shrub and young forest sites were replaced with 10 cm deep soil sources from corresponding later successional stage(s) in January 2009. Woody plant seed germination was monitored in the first year and seedling survival was monitored until the end of the second year. At the end of 2010, 2097 seeds of woody plants belonging to 45 taxa had germinated, and 3.9% of the seedlings and 7.8% of the species survived. Germination of most species was sensitive to ambient light (red, far-red, R:FR ratios, photosynthetically active radiation). Soil source and recipient site had a significant effect on the total number of seeds and number of species that germinated, and on the percentage of seedlings that survived through the end of the second year. Closer successional stages between recipient site and soil source had higher seed germination and seedling-survival percentages. However, a transition threshold exists in the young forest state, where seeds can germinate but not survive the second year. Our results, although based on an unreplicated chronosequence, suggest that successional distance between soil sources and recipient sites affect forest recruitment and restoration in degraded karst of SW China. PMID- 24223892 TI - Study of the HIV-2 Env cytoplasmic tail variability and its impact on Tat, Rev and Nef. AB - BACKGROUND: The HIV-2 env's 3' end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences. RESULTS: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn't observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don't impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together. CONCLUSION: The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don't affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT. PMID- 24223893 TI - Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms. AB - OBJECTIVE: We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. METHODS: Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. RESULTS: The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). CONCLUSIONS: The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines. PMID- 24223894 TI - C-Met as a prognostic marker in gastric cancer: a systematic review and meta analysis. AB - BACKGROUND: c-Met has been recognized as an important therapeutic target in gastric cancer, but the prognostic property of the c-Met status is still unclear. We aimed to characterize the prognostic effect of c-Met by systematic review and meta-analysis. METHODS: We identified 15 studies assessing survival in gastric cancer by c-Met status. Effect measure of interest was hazard ratio (HR) for survival. Meta-regression was performed to estimate the relationship between HR and disease stage. Random-effects meta-analyses were used to account for heterogeneity. RESULTS: 15 eligible studies provided outcome data stratified by c Met status in 2210 patients. Meta-analysis of the HRs indicated a significantly poorer Os in patients with high c-Met expression (average HR=2.112, 95%CI: 1.622 2.748). Subgroup analysis showed the prognostic effect of c-Met was identical in protein-level and gene-level based methodology. The same effect was also seen in Asian and Western ethnicity subgroup analysis. Meta-regression showed HR was not associated with disease stage. CONCLUSIONS: Patients with tumors that harbor high c-Met expression are more likely to have a worse Os, with this prognostic effect independent of disease stage. c-Met status should be evaluated in clinical prognosis. PMID- 24223895 TI - Zygotic Porcn paternal allele deletion in mice to model human focal dermal hypoplasia. AB - In mouse and humans, the X-chromosomal Porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands, thus representing a bottleneck in the secretion of Wnt ligands. In humans, mutations in PORCN cause the X-linked dominant syndrome Focal Dermal Hypoplasia (FDH, OMIM#305600). This disorder is characterized by ecto-mesodermal dysplasias and shows a highly variable phenotype, potentially due to individual X chromosome inactivation patterns. To improve the understanding of human FDH, we have established a mouse model by generation of Porcn heterozygous animals carrying a zygotic deletion of the paternal allele. We show that heterozygous female fetuses display variable defects that do not significantly affect survival in the uterus, but lead to perinatal lethality in more than 95% of females. Rare survivors develop to adulthood and display variable skeletal and skin defects, representing an adult zygotic mouse model for human FDH. Although not frequently reported in humans, we also observed bronchopneumonia, rhinitis, and otitis media in these animals, suggesting a potential link between Porcn function and the normal development of ciliated cells in these tissues. PMID- 24223896 TI - DNA barcode identification of freshwater snails in the family Bithyniidae from Thailand. AB - Freshwater snails in the family Bithyniidae are the first intermediate host for Southeast Asian liver fluke (Opisthorchis viverrini), the causative agent of opisthorchiasis. Unfortunately, the subtle morphological characters that differentiate species in this group are not easily discerned by non-specialists. This is a serious matter because the identification of bithyniid species is a fundamental prerequisite for better understanding of the epidemiology of this disease. Because DNA barcoding, the analysis of sequence diversity in the 5' region of the mitochondrial COI gene, has shown strong performance in other taxonomic groups, we decided to test its capacity to resolve 10 species/ subspecies of bithyniids from Thailand. Our analysis of 217 specimens indicated that COI sequences delivered species-level identification for 9 of 10 currently recognized species. The mean intraspecific divergence of COI was 2.3% (range 0 9.2 %), whereas sequence divergences between congeneric species averaged 8.7% (range 0-22.2 %). Although our results indicate that DNA barcoding can differentiate species of these medically-important snails, we also detected evidence for the presence of one overlooked species and one possible case of synonymy. PMID- 24223897 TI - PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study. AB - A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg's and Egger's test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies. PMID- 24223898 TI - A novel electrocardiographic index for the diagnosis of diastolic dysfunction. AB - BACKGROUND: Although the assessment of diastolic dysfunction (DD) is an integral part of routine cardiologic examinations, little is known about associated electrocardiographic (ECG) changes. Our aim was to investigate a potential role of ECG indices for the recognition of patients with DD. METHODS AND RESULTS: ECG parameters correlating with echocardiographic findings of DD were retrospectively assessed in a derivation group of 172 individuals (83 controls with normal diastolic function, 89 patients with DD) and their diagnostic performance was tested in a validation group of 50 controls and 50 patients. The patient group with a DD Grade 1 and 2 showed longer QTc (422 +/- 24 ms and 434 +/- 32 ms vs. 409 +/- 25ms, p<0.0005) and shorter Tend-P and Tend-Q intervals, reflecting the electrical and mechanical diastole (240 +/- 78 ms and 276 +/- 108 ms vs. 373 +/- 110 ms, p<0.0001; 409 +/- 85 ms and 447 +/- 115 ms vs. 526 +/- 119 ms, p<0.0001). The PQ-interval was significantly longer in the patient group (169 +/- 28ms and 171 +/- 38ms vs. 153 +/- 22ms, p<0.005). After adjusting for possible confounders, a novel index (Tend-P/[PQxAge]) showed a high performance for the recognition of DD, stayed robust in the validation group (sensitivity 82%, specificity 93%, positive predictive value 93%, negative predictive value 82%, accuracy 88%) and proved a substantial added value when combined with the indexed left atrial volume (LAESVI, sensitivity 90%, specificity 92%, positive predictive value 95%, negative predictive value 86%, accuracy 91%). CONCLUSIONS: A novel electrocardiographic index Tend-P/(PQxAge) demonstrates a high diagnostic accuracy for the diagnosis of DD and yields a substantial added value when combined with the LAESVI. PMID- 24223899 TI - Chlorine dioxide is a size-selective antimicrobial agent. AB - BACKGROUND / AIMS: ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. METHODS: ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. RESULTS: The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e.g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. CONCLUSION: Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic. PMID- 24223900 TI - SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. AB - AIM: The role of Sirtuin 1 (SIRT 1) in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non small cell lung cancer (NSCLC). METHODS: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B) and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS) and progression free survival (PFS). In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA). The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice. RESULTS: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice. CONCLUSION: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC. PMID- 24223901 TI - Improving glyphosate oxidation activity of glycine oxidase from Bacillus cereus by directed evolution. AB - Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO) has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate. Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO), we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution. Six mutants exhibiting enhanced activity toward glyphosate were screened from two rounds of error-prone PCR combined with site directed mutagenesis, and the beneficial mutations of the six evolved variants were recombined by DNA shuffling. Four recombinants were generated and, when compared with the wild-type BceGO, the most active mutant B3S1 showed the highest activity, exhibiting a 160 fold increase in substrate affinity, a 326-fold enhancement in catalytic efficiency against glyphosate, with little difference between their pH and temperature stabilities. The role of these mutations was explored through structure modeling and molecular docking, revealing that the Arg(51) mutation is near the active site and could be an important residue contributing to the stabilization of glyphosate binding, while the role of the remaining mutations is unclear. These results provide insight into the application of directed evolution in optimizing glycine oxidase function and have laid a foundation for the development of glyphosate-tolerant crops. PMID- 24223902 TI - Predictors of response rates to a long term follow-up mail out survey. AB - OBJECTIVE: Very little is known about predictors of response rates to long-term follow-up mail-out surveys, including whether the timing of an incentive affects response rates. We aimed to determine whether the timing of the incentive affects response rates and what baseline demographic and psychological factors predict response rates to a 12 year follow-up survey. STUDY DESIGN AND SETTING: Participants were 450 randomly selected people from the Penrith population, Australia who had previously participated in a mail-out survey 12 years earlier. By random allocation, 150 people received no incentive, 150 received a lottery ticket inducement with the follow-up survey and 150 received a lottery ticket inducement on the return of a completed survey. RESULTS: The overall response rate for the study was 63%. There were no significant differences in terms of response rates between the no incentive (58.8%;95%CI 49.8%,67.3%), incentive with survey (65.1%;95%CI 56.2%,73.3%) and promised incentive (65.3%;95%CI 56.1%,73.7%) groups. Independent predictors of responding to the 12 year survey were being older (OR=1.02, 95%CI 1.01,1.05,P=0.001) and being less neurotic as reported on the first survey 12 years earlier (OR=0.92, 95%CI 0.86,0.98, P=0.010). CONCLUSIONS: Psychological factors may play a role in determining who responds to long-term follow-up surveys although timing of incentives does not. PMID- 24223903 TI - Neuroprotection in a novel mouse model of multiple sclerosis. AB - Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment. PMID- 24223904 TI - Estimated incidence and genotypes of HIV-1 among pregnant women in central Brazil. AB - OBJECTIVE: To estimate the incidence of HIV-1 infection among pregnant women from central-western Brazil. DESIGN: Observational cross-sectional study. METHODS: A total of 54,139 pregnant women received antenatal HIV screening from a network of public healthcare centers in 2011. The incidence of confirmed HIV-1 infection was estimated using the Serological Testing Algorithms for Recent HIV Seroconversion (STARHS) methodology and BED-capture enzyme immunoassay (BED-CEIA). The yearly incidence was calculated, and adjusted incidence rates were estimated. For a subgroup of patients, protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and sequenced after performing a nested polymerase chain reaction. RESULTS: Of the participants, 20% had a pregnancy before the age of 18 and approximately 40% were experiencing their first pregnancy. Of the 54,139 pregnant women screened, 86 had a confirmed HIV-1 diagnosis, yielding an overall prevalence of 1.59 cases per 1000 women (95% CI 1.27-1.96). A higher prevalence was detected in the older age groups, reflecting cumulative exposure to the virus over time. Among the infected pregnant women, 20% were considered recently infected according to the BED-CEIA. The estimated incidence of HIV infection was 0.61 per 1000 person-years (95% CI 0.33-0.89); the corrected incidence was 0.47 per 1000 person-years (95% CI 0.26-0.68). In a subgroup of patients, HIV-1 subtype C (16.7%) was the second most prevalent form after subtype B (66.7%); BF1 recombinants (11.1%) and one case of subtype F1 (5.5%) were also detected. CONCLUSION: This study highlights the potential for deriving incidence estimates from a large antenatal screening program for HIV. The rate of recent HIV-1 infection among women in their early reproductive years is a public health warning to implement preventive measures. PMID- 24223905 TI - Molecular dating of HIV-1 subtype C from Bangladesh. AB - Bangladesh has an overall low HIV prevalence of <0.1% in the general population and <1% among key affected populations, but it is one of few Asian countries that has yet to reverse the epidemic. In order to do this, it is important to understand the transmission dynamics in this country. The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh. The phylogenetic analysis included 118 Bangladeshi gag sequences and 128 sequences from other countries and was performed using the BEAST package. Our analysis revealed that the vast majority of Bangladeshi sequences (97/118, 82%) fall into a large regional cluster of samples from Bangladesh, India, China and Myanmar, which dates back to the early 1960's. Following its establishment in the region, this strain has entered Bangladesh multiple times from around 1975 and onwards, but extensive in-country transmission could only be detected among drug users and not through sexual transmission. In addition, there have been multiple (at least ten) introductions of subtype C to Bangladesh from outside this region, but no extensive spread could be detected for any of these. Since many HIV-infections remain undetected while asymptomatic, the true extent of the transmission of each strain remains unknown, especially among hard to reach groups such as clients of sex workers and returning migrants with families. PMID- 24223906 TI - Long-range dispersal and high-latitude environments influence the population structure of a "stress-tolerant" dinoflagellate endosymbiont. AB - The migration and dispersal of stress-tolerant symbiotic dinoflagellates (genus Symbiodinium) may influence the response of symbiotic reef-building corals to a warming climate. We analyzed the genetic structure of the stress-tolerant endosymbiont, Symbiodinium glynni nomen nudum (ITS2 - D1), obtained from Pocillopora colonies that dominate eastern Pacific coral communities. Eleven microsatellite loci identified genotypically diverse populations with minimal genetic subdivision throughout the Eastern Tropical Pacific, encompassing 1000's of square kilometers from mainland Mexico to the Galapagos Islands. The lack of population differentiation over these distances corresponds with extensive regional host connectivity and indicates that Pocillopora larvae, which maternally inherit their symbionts, aid in the dispersal of this symbiont. In contrast to its host, however, subtropical populations of S. glynni in the Gulf of California (Sea of Cortez) were strongly differentiated from populations in tropical eastern Pacific. Selection pressures related to large seasonal fluctuations in temperature and irradiance likely explain this abrupt genetic discontinuity. We infer that S. glynni genotypes harbored by host larvae arriving from more southern locations are rapidly replaced by genotypes adapted to more temperate environments. The strong population structure of S. glynni corresponds with fluctuating environmental conditions and suggests that these genetically diverse populations have the potential to evolve rapidly to changing environments and reveals the importance of environmental extremes in driving microbial eukaryote (e.g., plankton) speciation in marine ecosystems. PMID- 24223907 TI - Agonist antagonist interactions at the rapidly desensitizing P2X3 receptor. AB - P2X3 receptors (P2XRs), as members of the purine receptor family, are deeply involved in chronic pain sensation and therefore, specific, competitive antagonists are of great interest for perspective pain management. Heretofore, Schild plot analysis has been commonly used for studying the interaction of competitive antagonists and the corresponding receptor. Unfortunately, the steady state between antagonist and agonist, as a precondition for this kind of analysis, cannot be reached at fast desensitizing receptors like P2X3R making Schild plot analysis inappropriate. The aim of this study was to establish a new method to analyze the interaction of antagonists with their binding sites at the rapidly desensitizing human P2X3R. The patch-clamp technique was used to investigate the structurally divergent, preferential antagonists A317491, TNP-ATP and PPADS. The P2X1,3-selective alpha,beta-methylene ATP (alpha,beta-meATP) was used as an agonist to induce current responses at the wild-type (wt) P2X3R and several agonist binding site mutants. Afterwards a Markov model combining sequential transitions of the receptor from the closed to the open and desensitized mode in the presence or absence of associated antagonist molecules was developed according to the measured data. The P2X3R-induced currents could be fitted correctly with the help of this Markov model allowing identification of amino acids within the binding site which are important for antagonist binding. In conclusion, Markov models are suitable to simulate agonist antagonist interactions at fast desensitizing receptors such as the P2X3R. Among the antagonists investigated, TNP-ATP and A317491 acted in a competitive manner, while PPADS was identified as a (pseudo)irreversible blocker. PMID- 24223908 TI - Kinetics of MDR transport in tumor-initiating cells. AB - Multidrug resistance (MDR) driven by ABC (ATP binding cassette) membrane transporters is one of the major causes of treatment failure in human malignancy. MDR capacity is thought to be unevenly distributed among tumor cells, with higher capacity residing in tumor-initiating cells (TIC) (though opposite finding are occasionally reported). Functional evidence for enhanced MDR of TICs was previously provided using a "side population" assay. This assay estimates MDR capacity by a single parameter - cell's ability to retain fluorescent MDR substrate, so that cells with high MDR capacity ("side population") demonstrate low substrate retention. In the present work MDR in TICs was investigated in greater detail using a kinetic approach, which monitors MDR efflux from single cells. Analysis of kinetic traces obtained allowed for the estimation of both the velocity (V max) and affinity (K M) of MDR transport in single cells. In this way it was shown that activation of MDR in TICs occurs in two ways: through the increase of V max in one fraction of cells, and through decrease of K M in another fraction. In addition, kinetic data showed that heterogeneity of MDR parameters in TICs significantly exceeds that of bulk cells. Potential consequences of these findings for chemotherapy are discussed. PMID- 24223910 TI - Topological progression in proliferating epithelia is driven by a unique variation in polygon distribution. AB - Morphogenesis is consequence of lots of small coordinated variations that occur during development. In proliferating stages, tissue growth is coupled to changes in shape and organization. A number of studies have analyzed the topological properties of proliferating epithelia using the Drosophila wing disc as a model. These works are based in the existence of a fixed distribution of these epithelial cells according to their number of sides. Cell division, cell rearrangements or a combination of both mechanisms have been proposed to be responsible for this polygonal assembling. Here, we have used different system biology methods to compare images from two close proliferative stages that present high morphological similarity. This approach enables us to search for traces of epithelial organization. First, we show that geometrical and network characteristics of individual cells are mainly dependent on their number of sides. Second, we find a significant divergence between the distribution of polygons in epithelia from mid-third instar larva versus early prepupa. We show that this alteration propagates into changes in epithelial organization. Remarkably, only the variation in polygon distribution driven by morphogenesis leads to progression in epithelial organization. In addition, we identify the relevant features that characterize these rearrangements. Our results reveal signs of epithelial homogenization during the growing phase, before the planar cell polarity pathway leads to the hexagonal packing of the epithelium during pupal stages. PMID- 24223909 TI - Cyclopia extracts act as ERalpha antagonists and ERbeta agonists, in vitro and in vivo. AB - Hormone replacement therapy associated risks, and the concomitant reluctance of usage, has instigated the search for new generations of estrogen analogues that would maintain estrogen benefits without associated risks. Furthermore, if these analogues display chemo-preventative properties in breast and endometrial tissues it would be of great value. Both the selective estrogen receptor modulators as well as the selective estrogen receptor subtype modulators have been proposed as estrogen analogues with improved risk profiles. Phytoestrogen containing extracts of Cyclopia, an indigenous South African fynbos plant used to prepare Honeybush tea may serve as a source of new estrogen analogues. In this study three extracts, P104, SM6Met, and cup-of-tea, from two species of Cyclopia, C. genistoides and C. subternata, were evaluated for ER subtype specific agonism and antagonism both in transactivation and transrepression. For transactivation, the Cyclopia extracts displayed ERalpha antagonism and ERbeta agonism when ER subtypes were expressed separately, however, when co-expressed only agonism was uniformly observed. In contrast, for transrepression, this uniform behavior was lost, with some extracts (P104) displaying uniform agonism, while others (SM6Met) displayed antagonism when subtypes were expressed separately and agonism when co expressed. In addition, breast cancer cell proliferation assays indicate that extracts antagonize cell proliferation in the presence of estrogen at lower concentrations than that required for proliferation. Furthermore, lack of uterine growth and delayed vaginal opening in an immature rat uterotrophic model validates the ERalpha antagonism of extracts observed in vitro and supports the potential of the Cyclopia extracts as a source of estrogen analogues with a reduced risk profile. PMID- 24223911 TI - N-alkylated aminoacyl sulfamoyladenosines as potential inhibitors of aminoacylation reactions and microcin C analogues containing D-amino acids. AB - Microcin C analogues were recently envisaged as important compounds for the development of novel antibiotics. Two issues that may pose problems to these potential antibiotics are possible acquisition of resistance through acetylation and in vivo instability of the peptide chain. N-methylated aminoacyl sulfamoyladenosines were synthesized to investigate their potential as aminoacyl tRNA synthetase inhibitors and to establish whether these N-alkylated analogues would escape the natural inactivation mechanism via acetylation of the alpha amine. It was shown however, that these compounds are not able to effectively inhibit their respective aminoacyl tRNA synthetase. In addition, we showed that (D)-aspartyl-sulfamoyladenosine (i.e. with a (D)-configuration for the aspartyl moiety), is a potent inhibitor of aspartyl tRNA synthetase. However, we also showed that the inhibitory effect of (D)- aspartyl-sulfamoyladenosine is relatively short-lasting. Microcin C analogues with (D)-amino acids throughout from positions two to six proved inactive. They were shown to be resistant against metabolism by the different peptidases and therefore not able to release the active moiety. This observation could not be reversed by incorporation of (L) amino acids at position six, showing that none of the available peptidases exhibit endopeptidase activity. PMID- 24223912 TI - Identification of new sphingomyelinases D in pathogenic fungi and other pathogenic organisms. AB - Sphingomyelinases D (SMases D) or dermonecrotic toxins are well characterized in Loxosceles spider venoms and have been described in some strains of pathogenic microorganisms, such as Corynebacterium sp. After spider bites, the SMase D molecules cause skin necrosis and occasional severe systemic manifestations, such as acute renal failure. In this paper, we identified new SMase D amino acid sequences from various organisms belonging to 24 distinct genera, of which, 19 are new. These SMases D share a conserved active site and a C-terminal motif. We suggest that the C-terminal tail is responsible for stabilizing the entire internal structure of the SMase D Tim barrel and that it can be considered an SMase D hallmark in combination with the amino acid residues from the active site. Most of these enzyme sequences were discovered from fungi and the SMase D activity was experimentally confirmed in the fungus Aspergillus flavus. Because most of these novel SMases D are from organisms that are endowed with pathogenic properties similar to those evoked by these enzymes alone, they might be associated with their pathogenic mechanisms. PMID- 24223913 TI - Short and long term outcome of bilateral pallidal stimulation in chorea acanthocytosis. AB - BACKGROUND: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. METHODS: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow up: 29.5 months). RESULTS: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (>= 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. CONCLUSION: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc. PMID- 24223914 TI - Proteomic identification of mitochondrial targets of arginase in human breast cancer. AB - We have previously reported arginase expression in human breast cancer cells and demonstrated that the inhibition of arginase by N(omega) hydroxy L-arginine (NOHA) in MDA-MB-468 cells induces apoptosis. However, arginase expression and its possible molecular targets in human breast tumor samples and potential clinical implications have not been fully elucidated. Here, we demonstrate arginase expression in human breast tumor samples, and several established breast cancer cell lines, in which NOHA treatment selectively inhibits cell proliferation. The over-expression of Bcl2 in MDA-MB-468 cells abolished NOHA induced apoptosis, suggesting that the mitochondria may be the main site of NOHA's action. We, therefore, undertook a proteomics approach to identify key mitochondrial targets of arginase in MDA-MB-468 cells. We identified 54 non mitochondrial and 13 mitochondrial proteins that were differentially expressed in control and NOHA treated groups. Mitochondrial serine hydroxymethyltransferase (mSHMT) was identified as one of the most promising targets of arginase. Both arginase II (Arg II) and mSHMT expressions were higher in human breast tumor tissues compared to the matched normal and there was a strong correlation between Arg II and mSHMT protein expression. MDA-MB-468 xenografts had significant upregulation of Arg II expression that preceded the induction of mSHMT expression. Small inhibitory RNA (siRNA)-mediated inhibition of Arg II in MDA-MB 468 and HCC-1806 cells led to significant inhibition of both the mSHMT gene and protein expression. As mSHMT is a key player in folate metabolism, our data provides a novel link between arginine and folate metabolism in human breast cancer, both of which are critical for tumor cell proliferation. PMID- 24223915 TI - Gamma-secretase components as predictors of breast cancer outcome. AB - gamma-secretase is a large ubiquitously expressed protease complex composed of four core subunits: presenilin, Aph1, PEN-2, and nicastrin. The function of gamma secretase in the cells is to proteolytically cleave various proteins within their transmembrane domains. Presenilin and Aph1 occur as alternative variants belonging to mutually exclusive gamma-secretase complexes and providing the complexes with heterogeneous biochemical and physiological properties. gamma secretase is proposed to have a role in the development and progression of cancer and gamma-secretase inhibitors are intensively studied for their probable anti tumor effects in various types of cancer models. Here, we for the first time determined mRNA expression levels of presenilin-1, presenilin-2, Aph1a, Aph1b, PEN-2, and nicastrin in a set of breast cancer tissue samples (N = 55) by quantitative real-time PCR in order to clarify the clinical significance of the expression of different gamma-secretase complex components in breast cancer. We found a high positive correlation between the subunit expression levels implying a common regulation of transcription. Our univariate Kaplan-Meier survival analyses established low expression level of gamma-secretase complex as a risk factor for breast cancer specific mortality. The tumors expressing low levels of gamma-secretase complex were characterized by high histopathological tumor grade, low or no expression of estrogen and progesterone receptors and consequently high probability to fall into the class of triple negative breast cancer tumors. These results may provide novel tools to further categorize breast cancer tumors, especially the highly aggressive and poorly treatable breast cancer type of triple negative cases, and suggest a significant role for gamma-secretase in breast cancer. PMID- 24223917 TI - Microbial environment affects innate immunity in two closely related earthworm species Eisenia andrei and Eisenia fetida. AB - Survival of earthworms in the environment depends on their ability to recognize and eliminate potential pathogens. This work is aimed to compare the innate defense mechanisms of two closely related earthworm species, Eisenia andrei and Eisenia fetida, that inhabit substantially different ecological niches. While E. andrei lives in a compost and manure, E. fetida can be found in the litter layer in forests. Therefore, the influence of environment-specific microbiota on the immune response of both species was followed. Firstly, a reliable method to discern between E. andrei and E. fetida based on species-specific primers for cytochrome c oxidase I (COI) and stringent PCR conditions was developed. Secondly, to analyze the immunological profile in both earthworm species, the activity and expression of lysozyme, pattern recognition protein CCF, and antimicrobial proteins with hemolytic function, fetidin and lysenins, have been assessed. Whereas, CCF and lysozyme showed only slight differences in the expression and activity, fetidin/lysenins expression as well as the hemolytic activity was considerably higher in E. andrei as compared to E. fetida. The expression of fetidin/lysenins in E. fetida was not affected upon the challenge with compost microbiota, suggesting more substantial changes in the regulation of the gene expression. Genomic DNA analyses revealed significantly higher level of fetidin/lysenins (determined using universal primer pairs) in E. andrei compared to E. fetida. It can be hypothesized that E. andrei colonizing compost as a new habitat acquired an evolutionary selection advantage resulting in a higher expression of antimicrobial proteins. PMID- 24223918 TI - Novel B19-like parvovirus in the brain of a harbor seal. AB - Using random PCR in combination with next-generation sequencing, a novel parvovirus was detected in the brain of a young harbor seal (Phoca vitulina) with chronic non-suppurative meningo-encephalitis that was rehabilitated at the Seal Rehabilitation and Research Centre (SRRC) in the Netherlands. In addition, two novel viruses belonging to the family Anelloviridae were detected in the lungs of this animal. Phylogenetic analysis of the coding sequence of the novel parvovirus, tentatively called Seal parvovirus, indicated that this virus belonged to the genus Erythrovirus, to which human parvovirus B19 also belongs. Although no other seals with similar signs were rehabilitated in SRRC in recent years, a prevalence study of tissues of seals from the same area collected in the period 2008-2012 indicated that the Seal parvovirus has circulated in the harbor seal population at least since 2008. The presence of the Seal parvovirus in the brain was confirmed by real-time PCR and in vitro replication. Using in situ hybridization, we showed for the first time that a parvovirus of the genus Erythrovirus was present in the Virchow-Robin space and in cerebral parenchyma adjacent to the meninges. These findings showed that a parvovirus of the genus Erythrovirus can be involved in central nervous system infection and inflammation, as has also been suspected but not proven for human parvovirus B19 infection. PMID- 24223919 TI - Determining the effects of cattle grazing treatments on Yosemite toads (Anaxyrus [=Bufo] canorus) in montane meadows. AB - Amphibians are experiencing a precipitous global decline, and population stability on public lands with multiple uses is a key concern for managers. In the Sierra Nevada Mountains (California, USA), managers have specifically identified livestock grazing as an activity that may negatively affect Yosemite toads due to the potential overlap of grazing with toad habitat. Grazing exclusion from Yosemite toad breeding and rearing areas and/or entire meadows have been proposed as possible management actions to alleviate the possible impact of cattle on this species. The primary objective of this study was to determine if different fencing treatments affect Yosemite toad populations. We specifically examined the effect of three fencing treatments on Yosemite toad breeding pool occupancy, tadpoles, and young of the year (YOY). Our hypothesis was that over the course of treatment implementation (2006 through 2010), Yosemite toad breeding pool occupancy and early life stage densities would increase within two fencing treatments relative to actively grazed meadows due to beneficial changes to habitat quality in the absence of grazing. Our results did not support our hypothesis, and showed no benefit to Yosemite toad presence or early life stages in fenced or partially fenced meadows compared to standard USDA Forest Service grazing levels. We found substantial Yosemite toad variation by both meadow and year. This variation was influenced by meadow wetness, with water table depth significant in both the tadpole and YOY models. PMID- 24223920 TI - Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the beta2 nicotinic acetylcholine receptor. AB - BACKGROUND: The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR). This concept has however not been demonstrated at a cellular level in intact tissue. To this end, we have studied the effect of nicotine on the activation of resident macrophages in a mouse stomach preparation by means of calcium imaging. METHODS: Calcium transients ([Ca(2+)]i) in resident macrophages were recorded in a mouse stomach preparation containing myenteric plexus and muscle layers by Fluo-4. Activation of macrophages was achieved by focal puff administration of ATP. The effects of nicotine on activation of macrophages were evaluated and the nAChR involved was pharmacologically characterized. The proximity of cholinergic nerves to macrophages was quantified by confocal microscopy. Expression of beta2 and alpha7 nAChR was evaluated by beta2 immunohistochemistry and fluorophore-tagged alpha bungarotoxin. RESULTS: In 83% of macrophages cholinergic varicose nerve fibers were detected at distances <900 nm. The ATP induced [Ca(2+)]i increase was significantly inhibited in 65% or 55% of macrophages by 100 uM or 10 uM nicotine, respectively. This inhibitory effect was reversed by the beta2 nAChR preferring antagonist dihydro-beta-eryhtroidine but not by hexamethonium (non-selective nAChR-antagonist), mecamylamine (alpha3beta4 nAChR-preferring antagonist), alpha bungarotoxin or methyllycaconitine (both alpha7 nAChR-preferring antagonist). Macrophages in the stomach express beta2 but not alpha7 nAChR at protein level, while those in the intestine express both receptor subunits. CONCLUSION: This study is the first in situ demonstration of an inhibition of macrophage activation by nicotine suggesting functional signaling between cholinergic neurons and macrophages in the stomach. The data suggest that the beta2 subunit of the nAChR is critically involved in the nicotine-induced inhibition of these resident macrophages. PMID- 24223922 TI - Practical role of mutation analysis for imatinib treatment in patients with advanced gastrointestinal stromal tumors: a meta-analysis. AB - BACKGROUND: Imatinib has become the standard first line treatment of gastrointestinal stromal tumors (GIST) in the advanced phase and adjuvant setting. We carried out an up-to-date meta-analysis to determine the practical role of mutation analysis for imatinib treatment in patients with advanced GIST. METHODS: Eligible studies were limited to imatinib treatment for patients with advanced GIST and reported on mutation analysis. Statistical analyses were conducted to calculate the odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) using fixed-effects and random-effects models. RESULTS: A total of 2834 patients from 3 randomized controlled trials and 12 cohort studies were included. The ORs of response rates in KIT exon 11-mutant GISTs were 3.504 (95% CI 2.549-4.816, p<0.001) and 3.521 (95% CI 1.731-7.165, p=0.001) compared with KIT exon 9-mutant and wild type GISTs, respectively. The HRs of progression-free survival in KIT exon 11-mutant GISTs were 0.365 (95% CI 0.301-0.444, p<0.001) and 0.375 (95% CI 0.270-0.519, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. The HRs of overall survival in KIT exon 11-mutant GISTs were 0.388 (95% CI 0.293-0.515, p<0.001) and 0.400 (95% CI 0.297-0.538, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. No statistical significant differences were found between KIT exon 9-mutant and wild type. The overall response rate in KIT exon 11-mutant GISTs were 70.5% (65%-75.9%) compared with 57.1% (51%-63.2%) in KIT-positive GISTs. No evidence of publication bias was observed. CONCLUSION: Patients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Mutation analysis would be more helpful than KIT expression analysis to decide appropriate therapy for a specific patient. PMID- 24223921 TI - Relating inter-individual differences in verbal creative thinking to cerebral structures: an optimal voxel-based morphometry study. AB - Creativity can be defined the capacity of an individual to produce something original and useful. An important measurable component of creativity is divergent thinking. Despite existing studies on creativity-related cerebral structural basis, no study has used a large sample to investigate the relationship between individual verbal creativity and regional gray matter volumes (GMVs) and white matter volumes (WMVs). In the present work, optimal voxel-based morphometry (VBM) was employed to identify the structure that correlates verbal creativity (measured by the verbal form of Torrance Tests of Creative Thinking) across the brain in young healthy subjects. Verbal creativity was found to be significantly positively correlated with regional GMV in the left inferior frontal gyrus (IFG), which is believed to be responsible for language production and comprehension, new semantic representation, and memory retrieval, and in the right IFG, which may involve inhibitory control and attention switching. A relationship between verbal creativity and regional WMV in the left and right IFG was also observed. Overall, a highly verbal creative individual with superior verbal skills may demonstrate a greater computational efficiency in the brain areas involved in high-level cognitive processes including language production, semantic representation and cognitive control. PMID- 24223916 TI - Comparison of mutation patterns in full-genome A/H3N2 influenza sequences obtained directly from clinical samples and the same samples after a single MDCK passage. AB - Human influenza viruses can be isolated efficiently from clinical samples using Madin-Darby canine kidney (MDCK) cells. However, this process is known to induce mutations in the virus as it adapts to this non-human cell-line. We performed a systematic study to record the pattern of MDCK-induced mutations observed across the whole influenza A/H3N2 genome. Seventy-seven clinical samples collected from 2009-2011 were included in the study. Two full influenza genomes were obtained for each sample: one from virus obtained directly from the clinical sample and one from the matching isolate cultured in MDCK cells. Comparison of the full genome sequences obtained from each of these sources showed that 42% of the 77 isolates had acquired at least one MDCK-induced mutation. The presence or absence of these mutations was independent of viral load or sample origin (in-patients versus out-patients). Notably, all the five hemagglutinin missense mutations were observed at the hemaggutinin 1 domain only, particularly within or proximal to the receptor binding sites and antigenic site of the virus. Furthermore, 23% of the 77 isolates had undergone a MDCK-induced missense mutation, D151G/N, in the neuraminidase segment. This mutation has been found to be associated with reduced drug sensitivity towards the neuraminidase inhibitors and increased viral receptor binding efficiency to host cells. In contrast, none of the neuraminidase sequences obtained directly from the clinical samples contained the D151G/N mutation, suggesting that this mutation may be an indicator of MDCK culture induced changes. These D151 mutations can confound the interpretation of the hemagglutination inhibition assay and neuraminidase inhibitor resistance results when these are based on MDCK isolates. Such isolates are currently in routine use in the WHO influenza vaccine and drug-resistance surveillance programs. Potential data interpretation miscalls can therefore be avoided by careful exclusion of such D151 mutants after further sequence analysis. PMID- 24223923 TI - Viral IRES prediction system - a web server for prediction of the IRES secondary structure in silico. AB - The internal ribosomal entry site (IRES) functions as cap-independent translation initiation sites in eukaryotic cells. IRES elements have been applied as useful tools for bi-cistronic expression vectors. Current RNA structure prediction programs are unable to predict precisely the potential IRES element. We have designed a viral IRES prediction system (VIPS) to perform the IRES secondary structure prediction. In order to obtain better results for the IRES prediction, the VIPS can evaluate and predict for all four different groups of IRESs with a higher accuracy. RNA secondary structure prediction, comparison, and pseudoknot prediction programs were implemented to form the three-stage procedure for the VIPS. The backbone of VIPS includes: the RNAL fold program, aimed to predict local RNA secondary structures by minimum free energy method; the RNA Align program, intended to compare predicted structures; and pknotsRG program, used to calculate the pseudoknot structure. VIPS was evaluated by using UTR database, IRES database and Virus database, and the accuracy rate of VIPS was assessed as 98.53%, 90.80%, 82.36% and 80.41% for IRES groups 1, 2, 3, and 4, respectively. This advance useful search approach for IRES structures will facilitate IRES related studies. The VIPS on-line website service is available at http://140.135.61.250/vips/. PMID- 24223924 TI - Bonobos protect and console friends and kin. AB - Post-conflict third-party affiliation has been reported to have different functional meanings, one of them being consolation. Here, we tested the main hypotheses that have been put forth to explain the presence of this phenomenon at a functional level in the bonobo: Self-Protection Hypothesis, Victim-Protection Hypothesis, Relationship-Repair or Substitute for Reconciliation Hypothesis, and Consolation Hypothesis. By analyzing the data collected over 10 years, we investigated what factors affected the distribution of both spontaneous third party affiliation (initiated by the bystander) and solicited third party affiliation (initiated by the victim). We considered factors related to the individual features (sex, rank, age) of victim and bystander, their relationship quality (kinship, affiliation), and the effect that third party affiliation had on the victim (such as protection against further attacks and anxiety reduction). Both spontaneous and solicited third party affiliation reduced the probability of further aggression by group members on the victim (Victim-Protection Hypothesis supported). Yet, only spontaneous affiliation reduced victim anxiety (measured via self-scratching), thus suggesting that the spontaneous gesture--more than the protection itself--works in calming the distressed subject. The victim may perceive the motivational autonomy of the bystander, who does not require an invitation to provide post-conflict affiliative contact. Moreover, spontaneous- but not solicited--third party affiliation was affected by the bond between consoler and victim, being the relationship between consoler and aggressor irrelevant to the phenomenon distribution (Consolation Hypothesis supported). Spontaneous affiliation followed the empathic gradient described for humans, being mostly offered to kin, then friends, then acquaintances. Overall, our findings do not only indicate the consolatory function of spontaneous third-party affiliation but they also suggest that consolation in the bonobo may be an empathy-based phenomenon. PMID- 24223925 TI - A multilocus phylogeny of the world Sycoecinae fig wasps (Chalcidoidea: Pteromalidae). AB - The Sycoecinae is one of five chalcid subfamilies of fig wasps that are mostly dependent on Ficus inflorescences for reproduction. Here, we analysed two mitochondrial (COI, Cytb) and four nuclear genes (ITS2, EF-1alpha, RpL27a, mago nashi) from a worldwide sample of 56 sycoecine species. Various alignment and partitioning strategies were used to test the stability of major clades. All topologies estimated using maximum likelihood and Bayesian methods were similar and well resolved but did not support the existing classification. A high degree of morphological convergence was highlighted and several species appeared best described as species complexes. We therefore proposed a new classification for the subfamily. Our analyses revealed several cases of probable speciation on the same host trees (up to 8 closely related species on one single tree of F. sumatrana), which raises the question of how resource partitioning occurs to avoid competitive exclusion. Comparisons of our results with fig phylogenies showed that, despite sycoecines being internally ovipositing wasps host-switches are common incidents in their evolutionary history. Finally, by studying the evolutionary properties of the markers we used and profiling their phylogenetic informativeness, we predicted their utility for resolving phylogenetic relationships of Chalcidoidea at various taxonomic levels. PMID- 24223926 TI - An integrated model of the transcriptome of HER2-positive breast cancer. AB - Our goal in these analyses was to use genomic features from a test set of primary breast tumors to build an integrated transcriptome landscape model that makes relevant hypothetical predictions about the biological and/or clinical behavior of HER2-positive breast cancer. We interrogated RNA-Seq data from benign breast lesions, ER+, triple negative, and HER2-positive tumors to identify 685 differentially expressed genes, 102 alternatively spliced genes, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were associated with the HER2-positive tumors in our survey panel. These features were integrated into a transcriptome landscape model that identified 12 highly interconnected genomic modules, each of which represents a cellular processes pathway that appears to define the genomic architecture of the HER2-positive tumors in our test set. The generality of the model was confirmed by the observation that several key pathways were enriched in HER2-positive TCGA breast tumors. The ability of this model to make relevant predictions about the biology of breast cancer cells was established by the observation that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. Additional modules from the HER2 transcriptome model, including ubiquitin mediated proteolysis, TGF-beta signaling, RHO-family GTPase signaling, and M phase progression, were linked to response to lapatinib and paclitaxel in vitro and/or risk of relapse in the N9831 dataset. These data indicate that an integrated transcriptome landscape model derived from a test set of HER2-positive breast tumors has potential for predicting outcome and for identifying novel potential therapeutic strategies for this breast cancer subtype. PMID- 24223927 TI - NMDA receptor antagonist ketamine impairs feature integration in visual perception. AB - Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans. PMID- 24223928 TI - Synergistic interactions between cytokines and AVP at the blood-CSF barrier result in increased chemokine production and augmented influx of leukocytes after brain injury. AB - Several lines of evidence indicate that the blood-cerebrospinal fluid barrier (BCSFB), which primarily resides in the choroid plexus (CP), plays a significant pathophysiological role not only in neuroinflammatory diseases, such as multiple sclerosis, but also in traumatic brain injury (TBI). Here we investigated how arginine vasopressin (AVP) regulates function of the BCSFB in the context of post traumatic neuroinflammation. It has previously been shown that AVP exacerbates various forms of brain injury, but the mechanisms underlying this AVP action are poorly understood. Type 1A AVP receptor is highly expressed on the CP epithelium and the CP synthesizes AVP. Using the controlled cortical impact model of TBI, we demonstrated decreased post-traumatic production of proinflammatory mediators by the CP and reduced influx of inflammatory cells across the BCSFB in AVP-deficient Brattleboro rats when compared with Long-Evans rats, a parental strain for Brattleboro rats. Arginine vasopressin was also found to play an important role in post-traumatic activation of c-Jun N-terminal kinase (JNK) in the CP. In the CP epithelial cell cultures, AVP augmented the tumor necrosis factor-alpha- and interleukin-1beta-dependent increase in synthesis of proinflammatory mediators, including neutrophil chemoattractants, an action largely dependent on the JNK signaling pathway. Under in vivo conditions, a selective JNK inhibitor decreased the post-traumatic production of neutrophil chemoattractants by the CP and reduced the influx of neutrophils across the BCSFB. These results provide evidence for the synergistic interactions between proinflammatory cytokines and AVP, a ligand for G protein-coupled receptors, and support a pathophysiological role of AVP in post-traumatic neuroinflammation. PMID- 24223929 TI - Roscovitine-induced apoptosis in neutrophils and neutrophil progenitors is regulated by the Bcl-2-family members Bim, Puma, Noxa and Mcl-1. AB - Neutrophil granulocyte (neutrophil) apoptosis plays a key role in determining inflammation in infectious and non-infectious settings. Recent work has shown that inhibitors of cyclin-dependent kinases (cdk) such as roscovitine can potently induce neutrophil apoptosis and reduce inflammation. Using a conditional Hoxb8-expression system we tested the participation of Bcl-2-family proteins to roscovitine-induced apoptosis in mouse neutrophils and in neutrophil progenitor cells. Bcl-2 strongly protected against roscovitine-induced apoptosis in neutrophils. The isolated loss of either Bim or noxa provided significant, partial protection while protection through combined loss of Bim and noxa or Bim and Puma was only slightly greater than this individual loss. The only substantial change in protein levels observed was the loss of Mcl-1, which was not transcriptional and was inhibited by proteasome blockade. In progenitor cells there was no protection by the loss of Bim alone but substantial protection by the loss of both Bim and Puma; surprisingly, strongest protection was seen by the isolated loss of noxa. The pattern of protein expression and Mcl-1-regulation in progenitor cells was very similar to the one observed in differentiated neutrophils. In addition, roscovitine strongly inhibited proliferation in progenitor cells, associated with an accumulation of cells in G2/M-phase. PMID- 24223930 TI - Role of FAAH-like anandamide transporter in anandamide inactivation. AB - The endocannabinoid system modulates numerous physiological processes including nociception and reproduction. Anandamide (AEA) is an endocannabinoid that is inactivated by cellular uptake followed by intracellular hydrolysis by fatty acid amide hydrolase (FAAH). Recently, FAAH-like anandamide transporter (FLAT), a truncated and catalytically-inactive variant of FAAH, was proposed to function as an intracellular AEA carrier and mediate its delivery to FAAH for hydrolysis. Pharmacological inhibition of FLAT potentiated AEA signaling and produced antinociceptive effects. Given that endocannabinoids produce analgesia through central and peripheral mechanisms, the goal of the current work was to examine the expression of FLAT in the central and peripheral nervous systems. In contrast to the original report characterizing FLAT, expression of FLAT was not observed in any of the tissues examined. To investigate the role of FLAT as a putative AEA binding protein, FLAT was generated from FAAH using polymerase chain reaction and further analyzed. Despite its low cellular expression, FLAT displayed residual catalytic activity that was sensitive to FAAH inhibitors and abolished following mutation of its catalytic serine. Overexpression of FLAT potentiated AEA cellular uptake and this appeared to be dependent upon its catalytic activity. Immunofluorescence revealed that FLAT localizes primarily to intracellular membranes and does not contact the plasma membrane, suggesting that its capability to potentiate AEA uptake may stem from its enzymatic rather than transport activity. Collectively, our data demonstrate that FLAT does not serve as a global intracellular AEA carrier, although a role in mediating localized AEA inactivation in mammalian tissues cannot be ruled out. PMID- 24223931 TI - Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival. AB - Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M. PMID- 24223932 TI - Conformational analysis of isolated domains of Helicobacter pylori CagA. AB - The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA)-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions. PMID- 24223933 TI - Circulating CD4+CD161+ T lymphocytes are increased in seropositive arthralgia patients but decreased in patients with newly diagnosed rheumatoid arthritis. AB - Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints. Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients. In contrast, circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count. Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis. In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells. Notably, synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidenced by increased interferon-gamma expression. The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention. PMID- 24223934 TI - An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction. AB - Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate--the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs. PMID- 24223935 TI - Risk factors and indices of osteomyelitis of the jaw in osteoporosis patients: results from a hospital-based cohort study in Japan. AB - BACKGROUND: Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients. METHODS: We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis. RESULTS: In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718). CONCLUSIONS: Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence. PMID- 24223936 TI - Visual exploratory search of relationship graphs on smartphones. AB - This paper presents a novel framework for Visual Exploratory Search of Relationship Graphs on Smartphones (VESRGS) that is composed of three major components: inference and representation of semantic relationship graphs on the Web via meta-search, visual exploratory search of relationship graphs through both querying and browsing strategies, and human-computer interactions via the multi-touch interface and mobile Internet on smartphones. In comparison with traditional lookup search methodologies, the proposed VESRGS system is characterized with the following perceived advantages. 1) It infers rich semantic relationships between the querying keywords and other related concepts from large scale meta-search results from Google, Yahoo! and Bing search engines, and represents semantic relationships via graphs; 2) the exploratory search approach empowers users to naturally and effectively explore, adventure and discover knowledge in a rich information world of interlinked relationship graphs in a personalized fashion; 3) it effectively takes the advantages of smartphones' user friendly interfaces and ubiquitous Internet connection and portability. Our extensive experimental results have demonstrated that the VESRGS framework can significantly improve the users' capability of seeking the most relevant relationship information to their own specific needs. We envision that the VESRGS framework can be a starting point for future exploration of novel, effective search strategies in the mobile Internet era. PMID- 24223937 TI - Serotonin receptor B may lock the gate of PTTH release/synthesis in the Chinese silk moth, Antheraea pernyi; a diapause initiation/maintenance mechanism? AB - The release of prothoracicotropic hormone, PTTH, or its blockade is the major endocrine switch regulating the developmental channel either to metamorphosis or to pupal diapause in the Chinese silk moth, Antheraea pernyi. We have cloned cDNAs encoding two types of serotonin receptors (5HTRA and B). 5HTRA-, and 5HTRB like immunohistochemical reactivities (-ir) were colocalized with PTTH-ir in two pairs of neurosecretory cells at the dorsolateral region of the protocerebrum (DL). Therefore, the causal involvement of these receptors was suspected in PTTH release/synthesis. The level of mRNA(5HTRB) responded to 10 cycles of long-day activation, falling to 40% of the original level before activation, while that of 5HTRA was not affected by long-day activation. Under LD 16:8 and 12:12, the injection of dsRNA(5HTRB) resulted in early diapause termination, whereas that of dsRNA(5HTRA) did not affect the rate of diapause termination. The injection of dsRNA(5HTRB) induced PTTH accumulation, indicating that 5HTRB binding suppresses PTTH synthesis also. This conclusion was supported pharmacologically; the injection of luzindole, a melatonin receptor antagonist, plus 5th inhibited photoperiodic activation under LD 16:8, while that of 5,7-DHT, induced emergence in a dose dependent fashion under LD 12:12. The results suggest that 5HTRB may lock the PTTH release/synthesis, maintaining diapause. This could also work as diapause induction mechanism. PMID- 24223938 TI - Temporal intra-individual variation of immunological biomarkers in type 1 diabetes patients: implications for future use in cross-sectional assessment. AB - Multiple immune parameters such as frequencies of autoreactive CD4(+), CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) T-cells have been explored as biomarkers in human T1D. However, intra-individual temporal variation of these parameters has not been assessed systematically over time. We determined the variation in each of these parameters in a cohort of T1D and healthy donors (HDs), at monthly intervals for one year. Despite low intra- and inter-assay co-efficient of variation (CV), mean CVs for each of the immune parameters were 119.1% for CD4(+) T-cell-derived IFN-gamma, 50.44% for autoreactive CD8(+) T-cells, and 31.24% for CD4(+)CD25(+)Foxp3(+) T-cells. Further, both HDs and T1D donors had similar CVs. The variation neither correlated with BMI, age, disease duration or insulin usage, nor were there detectable cyclical patterns of variation. However, averaging results from multiple visits for an individual provided a better estimate of the CV between visits. Based on our data we predict that by averaging values from three visits a treatment effect on these parameters with a 50% effect size could be detected with the same power using 1.8-4-fold fewer patients within a trial compared to using values from a single visit. Thus, our present data contribute to a more robust, accurate endpoint design for future clinical trials in T1D and aid in the identification of truly efficacious therapies. PMID- 24223939 TI - The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti tumor effect. AB - p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH), as the ligand of Gonadotrophin releasing hormone receptor (GnRH-R), was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy. PMID- 24223940 TI - Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice. AB - Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics. PMID- 24223941 TI - Neuroprotective effects of ginsenoside Rb1 on high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons. AB - Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72 h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 MUM Rb1 for 72 h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction. PMID- 24223942 TI - Do aging and dual-tasking impair the capacity to store and retrieve visuospatial information needed to guide perturbation-evoked reach-to-grasp reactions? AB - A recent study involving young adults showed that rapid perturbation-evoked reach to-grasp balance-recovery reactions can be guided successfully with visuospatial information (VSI) retained in memory despite: 1) a reduction in endpoint accuracy due to recall-delay (time between visual occlusion and perturbation-onset, PO) and 2) slowing of the reaction when performing a concurrent cognitive task during the recall-delay interval. The present study aimed to determine whether this capacity is compromised by effects of aging. Ten healthy older adults were tested with the previous protocol and compared with the previously-tested young adults. Reactions to recover balance by grasping a small handhold were evoked by unpredictable antero-posterior platform-translation (barriers deterred stepping reactions), while using liquid-crystal goggles to occlude vision post-PO and for varying recall-delay times (0-10 s) prior to PO (the handhold was moved unpredictably to one of four locations 2 s prior to vision-occlusion). Subjects also performed a spatial- or non-spatial-memory cognitive task during the delay time in a subset of trials. Results showed that older adults had slower reactions than the young across all experimental conditions. Both age groups showed similar reduction in medio-lateral end-point accuracy when recall-delay was longest (10 s), but differed in the effect of recall delay on vertical hand elevation. For both age groups, engaging in either the non-spatial or spatial-memory task had similar (slowing) effects on the arm reactions; however, the older adults also showed a dual-task interference effect (poorer cognitive-task performance) that was specific to the spatial-memory task. This provides new evidence that spatial working memory plays a role in the control of perturbation-evoked balance recovery reactions. The delays in completing the reaction that occurred when performing either cognitive task suggest that such dual-task situations in daily life could increase risk of falling in seniors, particularly when combined with the general age-related slowing that was observed across all experimental conditions. PMID- 24223943 TI - An optimized whole-body cortisol quantification method for assessing stress levels in larval zebrafish. AB - Glucocorticoids serve important regulatory functions for many physiological processes and are critical mediators of the stress response. The stress response is a set of bodily processes aimed at counteracting a state of threatened homeostasis. Proper stress response is critical for the survival of an animal, however prolonged or abnormal stress response can be detrimental and is implicated in a number of human diseases such as depression and metabolic diseases. To dissect the underlying mechanism of this complex and important response, the zebrafish, Danio rerio offer important advantages such as ease of genetic manipulations and high-throughput behavioral analyses. However, there is a paucity of suitable methods to measure stress level in larval zebrafish. Therefore, an efficient low-cost method to monitor stress hormone levels will greatly facilitate stress research in zebrafish larvae. In this study, we optimized sample collection as well as cortisol extraction methods and developed a home-made ELISA protocol for measuring whole-body cortisol level in zebrafish larvae. Further, using our customized protocols, we characterized the response of larval zebrafish to a variety of stressors. This assay, developed for efficient cortisol quantification, will be useful for systematic and large-scale stress analyses in larval zebrafish. PMID- 24223944 TI - Leaves of the Arabidopsis maltose exporter1 mutant exhibit a metabolic profile with features of cold acclimation in the warm. AB - BACKGROUND: Arabidopsis plants accumulate maltose from starch breakdown during cold acclimation. The Arabidopsis mutant, maltose excess1-1, accumulates large amounts of maltose in the plastid even in the warm, due to a deficient plastid envelope maltose transporter. We therefore investigated whether the elevated maltose level in mex1-1 in the warm could result in changes in metabolism and physiology typical of WT plants grown in the cold. PRINCIPAL FINDINGS: Grown at 21 degrees C, mex1-1 plants were much smaller, with fewer leaves, and elevated carbohydrates and amino acids compared to WT. However, after transfer to 4 degrees C the total soluble sugar pool and amino acid concentration was in equal abundance in both genotypes, although the most abundant sugar in mex1-1 was still maltose whereas sucrose was in greatest abundance in WT. The chlorophyll a/b ratio in WT was much lower in the cold than in the warm, but in mex1-1 it was low in both warm and cold. After prolonged growth at 4 degrees C, the shoot biomass, rosette diameter and number of leaves at bolting were similar in mex1-1 and WT. CONCLUSIONS: The mex1-1 mutation in warm-grown plants confers aspects of cold acclimation, including elevated levels of sugars and amino acids and low chlorophyll a/b ratio. This may in turn compromise growth of mex1-1 in the warm relative to WT. We suggest that elevated maltose in the plastid could be responsible for key aspects of cold acclimation. PMID- 24223945 TI - Serum and lymphocytic neurotrophins profiles in systemic lupus erythematosus: a case-control study. AB - BACKGROUND: Neurotrophins play a central role in the development and maintenance of the nervous system. However, neurotrophins can also modulate B and T cell proliferation and activation, especially via autocrine loops. We hypothesized that both serum and lymphocytic neurotrophin levels may be deregulated in systemic Lupus erythematosus (SLE) and may reflect clinical symptoms of the disease. METHODS: Neurotrophins in the serum (ELISA tests) and lymphocytes (flow cytometry) were measured in 26 SLE patients and 26 control subjects. Th1 (interferon-gamma) and Th2 (IL-10) profiles and serum concentration of BAFF were assessed by ELISA in the SLE and control subjects. FINDINGS: We have demonstrated that both NGF and BDNF serum levels are higher in SLE patients than healthy controls (p=0.003 and p<0.001), independently of Th1 or Th2 profiles. Enhanced serum NT-3 levels (p=0.003) were only found in severe lupus flares (i.e. SLEDAI >= 10) and significantly correlated with complement activation (decreased CH 50, Gamma=-0.28, p=0.03). Furthermore, there was a negative correlation between serum NGF levels and the number of circulating T regulatory cells (Gamma=0.48, p=0.01). In circulating B cells, production of both NGF and BDNF was greater in SLE patients than in healthy controls. In particular, the number of NGF-secreting B cells correlated with decreased complement levels (p=0.05). One month after SLE flare treatment, BDNF levels decreased; in contrast, NGF and NT-3 levels remained unchanged. CONCLUSION: This study demonstrates that serum and B cell levels of both NGF and BDNF are increased in SLE, suggesting that the neurotrophin production pathway is deregulated in this disease. These results must be confirmed in a larger study with naive SLE patients, in order to avoid the potential confounding influence of prior immune-modulating treatments on neurotrophin levels. PMID- 24223947 TI - Cognitive performance of Gottingen minipigs is affected by diet in a spatial hole board discrimination test. AB - Consumption of a high energy diet, containing high amounts of saturated fat and refined sugar has been associated with impairment of cognitive function in rodents and humans. We sought to contrast the effect of a high fat/cholesterol, low carbohydrate diet and a low fat, high carbohydrate/sucrose diet, relative to a standard low fat, high carbohydrate minipig diet on spatial cognition with regards to working memory and reference memory in 24 male Gottingen minipigs performing in a spatial hole-board discrimination test. We found that both working memory and reference memory were impaired by both diets relative to a standard minipig diet high in carbohydrate, low in fat and sugar. The different diets did not impact levels of brain-derived neurotrophic factor in brain tissue and neither did they affect circulatory inflammation measured by concentrations of C-reactive protein and haptoglobin in serum. However, higher levels of triglycerides were observed for minipigs fed the diets with high fat/cholesterol, low carbohydrate and low fat, high carbohydrate/sucrose compared to minipigs fed a standard minipig diet. This might explain the observed impairments in spatial cognition. These findings suggest that high dietary intake of both fat and sugar may impair spatial cognition which could be relevant for mental functioning in humans. PMID- 24223946 TI - Clinical significance of ischemia-modified albumin in the diagnosis of doxorubicin-induced myocardial injury in breast cancer patients. AB - BACKGROUND: Ischemia-modified albumin is an altered serum albumin that forms under conditions of oxidative stress, a state also associated with doxorubicin induced myocardial injury. OBJECTIVE: The aim of this study was to better assess diagnostic and prognostic significance of ischemia-modified albumin in patients with breast cancer undergoing doxorubicin chemotherapy. METHODS: Blood samples were collected from 152 breast cancer patients before and after each cycle of doxorubicin chemotherapy to measure the serum levels of ischemia-modified albumin, cardiac troponin T and creatine kinase-MB. We also monitored cardiac function during a 12 month follow-up. RESULTS: There was a significant difference in ischemia-modified albumin levels before and after each cycle of chemotherapy and the ischemia-modified albumin concentration positively correlated with the cumulative dose of doxorubicin (r = 0.212, P < 0.05). The combination of ischemia modified albumin with cardiac troponin T and creatine kinase-MB increased the sensitivity to 0.920 and the specificity to 0.830 in the diagnosis of doxorubicin induced myocardial injury. The optimal cutoff for ischemia-modified albumin concentration was 112.09 U/ml. The rate of change for ischemia-modified albumin levels correlated negatively with the rate of change for left ventricular ejection fraction at one year (r = -0.221, P < 0.05). CONCLUSION: Ischemia modified albumin may be a clinically potential new marker for diagnosing doxorubicin-induced myocardial injury, and is helpful to predict long-term impairment of cardiac function. PMID- 24223948 TI - Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation. AB - Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/-)) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/-) mice. Brain TNF-alpha mRNA and protein expressions along with IL-1beta protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/-) mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-alpha and IL-1beta were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation. PMID- 24223949 TI - Microarray analysis of perinatal-estrogen-induced changes in gene expression related to brain sexual differentiation in mice. AB - Sexual dimorphism of the behaviors or physiological functions in mammals is mainly due to the sex difference of the brain. A number of studies have suggested that the brain is masculinized or defeminized by estradiol converted from testicular androgens in perinatal period in rodents. However, the mechanisms of estrogen action resulting in masculinization/defeminization of the brain have not been clarified yet. The large-scale analysis with microarray in the present study is an attempt to obtain the candidate gene(s) mediating the perinatal estrogen effect causing the brain sexual differentiation. Female mice were injected with estradiol benzoate (EB) or vehicle on the day of birth, and the hypothalamus was collected at either 1, 3, 6, 12, or 24 h after the EB injection. More than one hundred genes down-regulated by the EB treatment in a biphasic manner peaked at 3 h and 12-24 h after the EB treatment, while forty to seventy genes were constantly up-regulated after it. Twelve genes, including Ptgds, Hcrt, Tmed2, Klc1, and Nedd4, whose mRNA expressions were down-regulated by the neonatal EB treatment, were chosen for further examination by semiquantitative RT-PCR in the hypothalamus of perinatal intact male and female mice. We selected the genes based on the known profiles of their potential roles in brain development. mRNA expression levels of Ptgds, Hcrt, Tmed2, and Nedd4 were significantly lower in male mice than females at the day of birth, suggesting that the genes are down regulated by estrogen converted from testicular androgen in perinatal male mice. Some genes, such as Ptgds encoding prostaglandin D2 production enzyme and Hcrt encording orexin, have been reported to have a role in neuroprotection. Thus, Ptgds and Hcrt could be possible candidate genes, which may mediate the effect of perinatal estrogen responsible for brain sexual differentiation. PMID- 24223950 TI - Identification of a predicted trimeric autotransporter adhesin required for biofilm formation of Burkholderia pseudomallei. AB - The autotransporters are a large and diverse family of bacterial secreted and outer membrane proteins, which are present in many Gram-negative bacterial pathogens and play a role in numerous environmental and virulence-associated interactions. As part of a larger systematic study on the autotransporters of Burkholderia pseudomallei, the causative agent of the severe tropical disease melioidosis, we have constructed an insertion mutant in the bpss1439 gene encoding an unstudied predicted trimeric autotransporter adhesin. The bpss1439 mutant demonstrated a significant reduction in biofilm formation at 48 hours in comparison to its parent 10276 wild-type strain. This phenotype was complemented to wild-type levels by the introduction of a full-length copy of the bpss1439 gene in trans. Examination of the wild-type and bpss1439 mutant strains under biofilm-inducing conditions by microscopy after 48 hours confirmed that the bpss1439 mutant produced less biofilm compared to wild-type. Additionally, it was observed that this phenotype was due to low levels of bacterial adhesion to the abiotic surface as well as reduced microcolony formation. In a murine melioidosis model, the bpss1439 mutant strain demonstrated a moderate attenuation for virulence compared to the wild-type strain. This attenuation was abrogated by in trans complementation, suggesting that bpss1439 plays a subtle role in the pathogenesis of B. pseudomallei. Taken together, these studies indicate that BPSS1439 is a novel predicted autotransporter involved in biofilm formation of B. pseudomallei; hence, this factor was named BbfA, Burkholderia biofilm factor A. PMID- 24223951 TI - Fern spore longevity in saline water: can sea bottom sediments maintain a viable spore bank? AB - Freshwater and marine sediments often harbor reservoirs of plant diaspores, from which germination and establishment may occur whenever the sediment falls dry. Therewith, they form valuable records of historical inter- and intraspecific diversity, and are increasingly exploited to facilitate diversity establishment in new or restored nature areas. Yet, while ferns may constitute a considerable part of a vegetation's diversity and sediments are known to contain fern spores, little is known about their longevity, which may suffer from inundation and--in sea bottoms--salt stress. We tested the potential of ferns to establish from a sea or lake bottom, using experimental studies on spore survival and gametophyte formation, as well as a spore bank analysis on sediments from a former Dutch inland sea. Our experimental results revealed clear differences among species. For Asplenium scolopendrium and Gymnocarpium dryopteris, spore germination was not affected by inundated storage alone, but decreased with rising salt concentrations. In contrast, for Asplenium trichomanes subsp. quadrivalens germination decreased following inundation, but not in response to salt. Germination rates decreased with time of storage in saline water. Smaller and less viable gametophytes were produced when saline storage lasted for a year. Effects on germination and gametophyte development clearly differed among genotypes of A. scolopendrium. Spore bank analyses detected no viable spores in marine sediment layers. Only two very small gametophytes (identified as Thelypteris palustris via DNA barcoding) emerged from freshwater sediments. Both died before maturation. We conclude that marine, and likely even freshwater sediments, will generally be of little value for long-term storage of fern diversity. The development of any fern vegetation on a former sea floor will depend heavily on the deposition of spores onto the drained land by natural or artificial means of dispersal. PMID- 24223952 TI - The transcriptional landscape of Campylobacter jejuni under iron replete and iron limited growth conditions. AB - The genome-wide Campylobacter jejuni transcriptional response under iron replete and iron limited conditions was characterized using RNA-seq. We have identified 111 novel C. jejuni 5'UTRs and mapped 377 co-transcribed genes into 230 transcriptional operons. In contrast to previous microarray results, the C. jejuni iron stimulon is less extensive than previously believed and consists of 77 iron activated genes and 50 iron repressed genes. As anticipated, the iron repressed genes are primarily those involved in iron acquisition or oxidative stress defense. Interestingly, these experiments have revealed that iron is an important modulator of flagellar biogenesis with almost all the components of the flagella found to be iron activated. Given that motility is a well-known C. jejuni colonization factor, this suggests that there is an important regulatory coupling of flagellar biogenesis and iron level in C. jejuni. In addition we have identified several consensus mutations in the C. jejuni NCTC11168 strain that are widespread in the Campylobacter research community and which may explain conflicting phenotypic reports for this strain. Comparative analysis of iron responsive genes with the known Fur regulon indicates that many iron responsive genes are not Fur responsive; suggesting that additional iron regulatory factors remain to be characterized in C. jejuni. Further analysis of the RNA-seq data identified multiple novel transcripts including 19 potential ncRNAs. The expression of selected ncRNAs was confirmed and quantified with qRT-PCR. The qRT PCR results indicate that several of these novel transcripts are either Fur and/or iron responsive. The fact that several of these ncRNAs are iron responsive or Fur regulated suggests that they may perform regulatory roles in iron homeostasis. PMID- 24223953 TI - A Brain Motor Control Assessment (BMCA) protocol for upper limb function. AB - The Brain Motor Control Assessment (BMCA) protocol is a surface electromyography (sEMG)-based measure of motor output from central nervous system during a variety of reflex and voluntary motor tasks performed under strictly controlled conditions. The aim of this study was to evaluate the BMCA protocol for upper limb with the addition of shoulder voluntary tasks. The voluntary response index (VRI) was calculated from quantitative analysis of sEMG data during defined voluntary movement in neurologically intact people for comparison with that of patients after neurological injuries. The BMCA protocol included one bilateral and 4 unilateral voluntary tasks at different joints of both arms. The VRI, measured from 19 neurologically intact participants, comprises the total muscle activity recorded for the voluntary motor task (magnitude). The calculated similarity index (SI) for each phase of each task show the similarity of "the distribution of activity across the recorded muscles" for that task in this group off participants. RESULTS: The VRI magnitude values from right and left sides for different tasks showed no significant difference (ANOVA: FSide: 0.09, P = 0.77). Therefore these values were pooled before calculating SI. SI values were higher for tasks against gravity: elbow flexion (0.99+/-0.03), wrist flexion with palm up (0.98+/-0.03) and wrist extension with palm down (0.97+/-0.07). On the other hand, the SI values were the lowest for bilateral shoulder abduction (0.84+/ 0.08) and shoulder adduction (0.84+/-0.08). CONCLUSION: To validate this index for clinical use, serial studies on patients with neurological impairments should be performed. Tasks involving movement against gravity may be more suitable in future BMCAs. PMID- 24223954 TI - An HPLC-MS characterization of the changes in sweet orange leaf metabolite profile following infection by the bacterial pathogen Candidatus Liberibacter asiaticus. AB - Huanglongbing (HLB) presumably caused by Candidatus Liberibacter asiaticus (CLas) threatens the commercial U.S. citrus crop of an annual value of $3 billion. The earliest shift in metabolite profiles of leaves from greenhouse-grown sweet orange trees infected with Clas, and of healthy leaves, was characterized by HPLC MS concurrently with PCR testing for the presence of Clas bacteria and observation of disease symptoms. Twenty, 8-month-old 'Valencia' and 'Hamlin' trees were grafted with budwood from PCR-positive HLB source trees. Five graft inoculated trees of each variety and three control trees were sampled biweekly and analyzed by HPLC-MS and PCR. Thirteen weeks after inoculation, Clas was detected in newly growing flushes in 33% and 55% of the inoculated 'Hamlin' and 'Valencia' trees, respectively. Inoculated trees remained asymptomatic in the first 20 weeks, but developed symptoms 30 weeks after grafting. No significant differences in the leaf metabolite profiles were detected in Clas-infected trees 23 weeks after inoculation. However, 27 weeks after inoculation, differences in metabolite profiles between control leaves and those of Clas-infected trees were evident. Affected compounds were identified with authentic standards or structurally classified by their UV and mass spectra. Included among these compounds are flavonoid glycosides, polymethoxylated flavones, and hydroxycinnamates. Four structurally related hydroxycinnamate compounds increased more than 10-fold in leaves from 'Hamlin' and 'Valencia' sweet orange trees in response to Clas infection. Possible roles of these hydroxycinnamates as plant defense compounds against the Clas infection are discussed. PMID- 24223955 TI - Menaquinone and iron are essential for complex colony development in Bacillus subtilis. AB - Cells of undomesticated species of Bacillus subtilis frequently form complex colonies during spreading on agar surfaces. Given that menaquinone is involved in another form of coordinated behavior, namely, sporulation, we looked for a possible role for menaquinone in complex colony development (CCD) in the B. subtilis strain NCIB 3610. Here we show that inhibition of menaquinone biosynthesis in B. subtilis indeed abolished its ability to develop complex colonies. Additionally some mutations of B. subtilis which confer defective CCD could be suppressed by menaquinone derivatives. Several such mutants mapped to the dhb operon encoding the genes responsible for the biosynthesis of the iron siderophore, bacillibactin. Our results demonstrate that both menaquinone and iron are essential for CCD in B. subtilis. PMID- 24223956 TI - Cryptic genetic diversity is paramount in small-bodied amphibians of the genus Euparkerella (Anura: Craugastoridae) endemic to the Brazilian Atlantic forest. AB - Morphological similarity associated to restricted distributions and low dispersal abilities make the direct developing "Terrarana" frogs of the genus Euparkerella a good model for examining diversification processes. We here infer phylogenetic relationships within the genus Euparkerella, using DNA sequence data from one mitochondrial and four nuclear genes coupled with traditional Bayesian phylogenetic reconstruction approaches and more recent coalescent methods of species tree inference. We also used Bayesian clustering analysis and a recent Bayesian coalescent-based approach specifically to infer species delimitation. The analysis of 39 individuals from the four known Euparkerella species uncovered high levels of genetic diversity, especially within the two previously morphologically-defined E. cochranae and E. brasiliensis. Within these species, the gene trees at five independent loci and trees from combined data (concatenated dataset and the species tree) uncovered six deeply diverged and geographically coherent evolutionary units, which may have diverged between the Miocene and the Pleistocene. These six units were also uncovered in the Bayesian clustering analysis, and supported by the Bayesian coalescent-based species delimitation (BPP), and Genealogical Sorting Index (GSI), providing thus strong evidence for underestimation of the current levels of diversity within Euparkerella. The cryptic diversity now uncovered opens new opportunities to examine the origins and maintenance of microendemism in the context of spatial heterogeneity and/or human induced fragmentation of the highly threatened Brazilian Atlantic forest hotspot. PMID- 24223957 TI - Variance heterogeneity in Saccharomyces cerevisiae expression data: trans regulation and epistasis. AB - Here, we describe the results from the first variance heterogeneity Genome Wide Association Study (VGWAS) on yeast expression data. Using this forward genetics approach, we show that the genetic regulation of gene-expression in the budding yeast, Saccharomyces cerevisiae, includes mechanisms that can lead to variance heterogeneity in the expression between genotypes. Additionally, we performed a mean effect association study (GWAS). Comparing the mean and variance heterogeneity analyses, we find that the mean expression level is under genetic regulation from a larger absolute number of loci but that a higher proportion of the variance controlling loci were trans-regulated. Both mean and variance regulating loci cluster in regulatory hotspots that affect a large number of phenotypes; a single variance-controlling locus, mapping close to DIA2, was found to be involved in more than 10% of the significant associations. It has been suggested in the literature that variance-heterogeneity between the genotypes might be due to genetic interactions. We therefore screened the multi-locus genotype-phenotype maps for several traits where multiple associations were found, for indications of epistasis. Several examples of two and three locus genetic interactions were found to involve variance-controlling loci, with reports from the literature corroborating the functional connections between the loci. By using a new analytical approach to re-analyze a powerful existing dataset, we are thus able to both provide novel insights to the genetic mechanisms involved in the regulation of gene-expression in budding yeast and experimentally validate epistasis as an important mechanism underlying genetic variance-heterogeneity between genotypes. PMID- 24223958 TI - Fungal garden making inside bamboos by a non-social fungus-growing beetle. AB - In fungus-growing mutualism, it is indispensable for host animals to establish gardens of the symbiotic fungus as rapidly as possible. How to establish fungal gardens has been well-documented in social fungus-farming insects, whereas poorly documented in non-social fungus-farming insects. Here we report that the non social, fungus-growing lizard beetle Doubledaya bucculenta (Coleoptera: Erotylidae: Languriinae) transmits the symbiotic yeast Wickerhamomyces anomalus from the ovipositor-associated mycangium into bamboo internode cavities and disperses the yeast in the cavities to make gardens. Microbial isolation and cryo scanning electron microscopy observation revealed that W. anomalus was constantly located on the posterior ends of eggs, where larvae came out, and on the inner openings of oviposition holes. Direct observation of oviposition behavior inside internodes revealed that the distal parts of ovipositors showed a peristaltic movement when they were in contact with the posterior ends of eggs. Rearing experiments showed that W. anomalus was spread much more rapidly and widely on culture media and internodes in the presence of the larvae than in the absence. These results suggest that the ovipositors play a critical role in vertical transmission of W. anomalus and that the larvae contribute actively to the garden establishment, providing a novel case of fungal garden founding in non-social insect-fungus mutualism. PMID- 24223960 TI - Left atrial appendage volume increased in more than half of patients with cryptogenic stroke. AB - BACKGROUND: Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30-40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients. METHODS: This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices. RESULTS: In control subjects, mean LAA volume was 3.4+/-1.1 mL/m(2). Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m(2). In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7+/-2.0 mL/m(2) vs. 3.4+/-1.1 mL/m(2); P<0.001). Forty-five (55%) patients with cryptogenic stroke/TIA had enlarged LAA. CONCLUSION: LAA is significantly enlarged in more than half of patients with cryptogenic stroke/TIA. LAA thrombosis may contribute to the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation. PMID- 24223959 TI - Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. AB - Interferons (IFNs) are critical cytokines that regulate immune response against virus infections. Dengue virus (DV) infections are a major public health concern worldwide, and especially in Asia. In the present study, we investigated the effects and mechanisms of action of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in human lung epithelial cells. The results demonstrated that DV infection induced expression of several IFITs, including IFIT1, IFIT2, IFIT3, and IFIT5 in A549 cells. Induction of IFIT3 by DV infection was also observed in human dendritic cells. In a knockdown study, we showed that a signal transducer and activator of transcription 2 (STAT2), but not STAT1 or STAT3, regulated DV induced IFIT3 production. By using several different methods to evaluate cell death, we demonstrated that knockdown of IFIT3 led to cellular apoptosis. Furthermore, knockdown of IFIT3 induced the expression of several apoptotic regulators such as caspase 3, caspase 8, caspase 9, and Bcl-2-associated X protein (BAX). Such apoptotic effects and mechanisms were synergistically enhanced after DV infection. Moreover, under conditions of IFIT3 deficiency, viral production increased, suggesting an anti-viral effect of IFIT3. Interestingly, DV could suppress IFN-alpha-induced but not IFN-gamma-induced IFIT3 expression, a phenomenon similar to the regulation of STATs by DV. In conclusion, this study revealed some mechanisms of IFIT3 induction, and also demonstrated the protective roles of IFIT3 following IFN-alpha production in DV infection of human lung epithelial cells. PMID- 24223961 TI - DegS and RseP homologous proteases are involved in singlet oxygen dependent activation of RpoE in Rhodobacter sphaeroides. AB - Singlet oxygen ((1)O2) is the main agent of photooxidative stress and is generated by photosensitizers as (bacterio)chlorophylls. It leads to the damage of cellular macromolecules and therefore photosynthetic organisms have to mount an adaptive response to (1)O2 formation. A major player of the photooxidative stress response in Rhodobacter sphaeroides is the alternative sigma factor RpoE, which is inactivated under non-stress conditions by its cognate anti-sigma factor ChrR. By using random mutagenesis we identified RSP_1090 to be required for full activation of the RpoE response under (1)O2 stress, but not under organic peroxide stress. In this study we show that both RSP_1090 and RSP_1091 are required for full resistance towards (1)O2. Moreover, we revealed that the DegS and RseP homologs RSP_3242 and RSP_2710 contribute to (1)O2 resistance and promote ChrR proteolysis. The RpoE signaling pathway in R. sphaeroides is therefore highly similar to that of Escherichia coli, although very different anti-sigma factors control RpoE activity. Based on the acquired results, the current model for RpoE activation in response to (1)O2 exposure in R. sphaeroides was extended. PMID- 24223962 TI - Insight into the peopling of Mainland Southeast Asia from Thai population genetic structure. AB - There is considerable ethno-linguistic and genetic variation among human populations in Asia, although tracing the origins of this diversity is complicated by migration events. Thailand is at the center of Mainland Southeast Asia (MSEA), a region within Asia that has not been extensively studied. Genetic substructure may exist in the Thai population, since waves of migration from southern China throughout its recent history may have contributed to substantial gene flow. Autosomal SNP data were collated for 438,503 markers from 992 Thai individuals. Using the available self-reported regional origin, four Thai subpopulations genetically distinct from each other and from other Asian populations were resolved by Neighbor-Joining analysis using a 41,569 marker subset. Using an independent Principal Components-based unsupervised clustering approach, four major MSEA subpopulations were resolved in which regional bias was apparent. A major ancestry component was common to these MSEA subpopulations and distinguishes them from other Asian subpopulations. On the other hand, these MSEA subpopulations were admixed with other ancestries, in particular one shared with Chinese. Subpopulation clustering using only Thai individuals and the complete marker set resolved four subpopulations, which are distributed differently across Thailand. A Sino-Thai subpopulation was concentrated in the Central region of Thailand, although this constituted a minority in an otherwise diverse region. Among the most highly differentiated markers which distinguish the Thai subpopulations, several map to regions known to affect phenotypic traits such as skin pigmentation and susceptibility to common diseases. The subpopulation patterns elucidated have important implications for evolutionary and medical genetics. The subpopulation structure within Thailand may reflect the contributions of different migrants throughout the history of MSEA. The information will also be important for genetic association studies to account for population-structure confounding effects. PMID- 24223963 TI - Content-specificity in verbal recall: a randomized controlled study. AB - In this controlled experiment we examined whether there are content effects in verbal short-term memory and working memory for verbal stimuli. Thirty-seven participants completed forward and backward digit and letter recall tasks, which were constructed to control for distance effects between stimuli. A maximum likelihood mixed-effects logistic regression revealed main effects of direction of recall (forward vs backward) and content (digits vs letters). There was an interaction between type of recall and content, in which the recall of digits was superior to the recall of letters in verbal short-term memory but not in verbal working memory. These results demonstrate that the recall of information from verbal short-term memory is content-specific, whilst the recall of information from verbal working memory is content-general. PMID- 24223964 TI - Plasticity of migrating CD1b+ and CD1b- lymph dendritic cells in the promotion of Th1, Th2 and Th17 in response to Salmonella and helminth secretions. AB - Dendritic cells (DCs) are pivotal in the development of specific T-cell responses to control pathogens, as they govern both the initiation and the polarization of adaptive immunity. To investigate the capacities of migrating DCs to respond to pathogens, we used physiologically generated lymph DCs (L-DCs). The flexible polarization of L-DCs was analysed in response to Salmonella or helminth secretions known to induce different T cell responses. Mature conventional CD1b(+) L-DCs showed a predisposition to promote pro-inflammatory (IL-6), pro-Th1 (IL-12p40) and anti-inflammatory (IL-10) responses which were amplified by Salmonella, and limited to only IL-6 induction by helminth secretions. The other major population of L-DCs did not express the CD1b molecule and displayed phenotypic features of immaturity compared to CD1b(+) L-DCs. Salmonella infection reduced the constitutive expression of TNF-alpha and IL-4 mRNA in CD1b(-) L-DCs, whereas this expression was not affected by helminth secretions. The cytokine response of T cells promoted by L-DCs was analysed in T cell subsets after co culture with Salmonella or helminth secretion-driven CD1b(+) or CD1b(-) L-DCs. T cells preferentially expressed the IL-17 gene, and to a lesser extent the IFN gamma and IL-10 genes, in response to Salmonella-driven CD1b(+) L-DCs, whereas a preferential IL-10, IFN-gamma and IL-17 gene expression was observed in response to Salmonella-driven CD1b(-) L-DCs. In contrast, a predominant IL-4 and IL-13 gene expression by CD4(+) and CD8(+) T cells was observed after stimulation of CD1b(+) and CD1b(-) L-DCs with helminth secretions. These results show that mature conventional CD1b(+) L-DCs maintain a flexible capacity to respond differently to pathogens, that the predisposition of CD1b(-) L-DCs to promote a Th2 response can be oriented towards other Th responses, and finally that the modulation of migrating L-DCs responses is controlled more by the pathogen encountered than the L-DC subsets. PMID- 24223966 TI - Assessing the necessity of the standardized infection ratio for reporting central line-associated bloodstream infections. AB - This brief article presents results that support the contention that risk adjustment via the standardized infection ratio (SIR) for the reporting of central line-associated bloodstream infections (CLABSIs) may be no more predictive than standard rate adjustments utilizing CLABSIs per central line days (i.e., CLABSI rates). Recent data posted on the U.S. Department of Health and Human Services' Hospital Compare website showed that nearly 70% of 1721 reporting hospitals with at least 1000 central line days had five or fewer infections during 2011. These hospitals had 39.3% of the total central line days and a significantly lower SIR than poorer performing hospitals with six or more CLABSIs (p<0.0001). In addition, 19 hospitals are presented which had central line days between 9000 to over 22,000 that also had zero to three CLABSIs. Some of these hospitals were university referral centers and inner city facilities. There was great variation of CLABSI cases among US hospitals. Evidence is mounting that all hospitals should be able to achieve a near zero incidence of CLABSIs and that these infections may in fact be near 'never events', which begs whether risk adjustment with the SIR is needed and whether it adds more information than does rate adjustment using CLABSI rates. PMID- 24223965 TI - Role of TRPM7 channels in hyperglycemia-mediated injury of vascular endothelial cells. AB - This study investigated the change of transient receptor potential melastatin 7 (TRPM7) expression by high glucose and its role in hyperglycemia induced injury of vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated in the presence or absence of high concentrations of D-glucose (HG) for 72 h. RT-PCR, Real-time PCR, Western blotting, Immunofluorescence staining and whole-cell patch-clamp recordings showed that TRPM7 mRNA, TRPM7 protein expression and TRPM7-like currents were increased in HUVECs following exposure to HG. In contrast to D-glucose, exposure of HUVECs to high concentrations of L-glucose had no effect. HG increased reactive oxygen species (ROS) generation, cytotoxicity and decreased endothelial nitric oxide synthase protein expression, which could be attenuated by knockdown of TRPM7 with TRPM7 siRNA. The protective effect of silencing TRPM7 against HG induced endothelial injury was abolished by U0126, an inhibitor of the extracellular signal-regulated kinase signaling pathway. These observations suggest that TRPM7 channels play an important role in hyperglycemia-induced injury of vascular endothelial cells. PMID- 24223967 TI - Unmanned aerial vehicles (UAVs) for surveying marine fauna: a dugong case study. AB - Aerial surveys of marine mammals are routinely conducted to assess and monitor species' habitat use and population status. In Australia, dugongs (Dugong dugon) are regularly surveyed and long-term datasets have formed the basis for defining habitat of high conservation value and risk assessments of human impacts. Unmanned aerial vehicles (UAVs) may facilitate more accurate, human-risk free, and cheaper aerial surveys. We undertook the first Australian UAV survey trial in Shark Bay, western Australia. We conducted seven flights of the ScanEagle UAV, mounted with a digital SLR camera payload. During each flight, ten transects covering a 1.3 km(2) area frequently used by dugongs, were flown at 500, 750 and 1000 ft. Image (photograph) capture was controlled via the Ground Control Station and the capture rate was scheduled to achieve a prescribed 10% overlap between images along transect lines. Images were manually reviewed post hoc for animals and scored according to sun glitter, Beaufort Sea state and turbidity. We captured 6243 images, 627 containing dugongs. We also identified whales, dolphins, turtles and a range of other fauna. Of all possible dugong sightings, 95% (CI = 90%, 98%) were subjectively classed as 'certain' (unmistakably dugongs). Neither our dugong sighting rate, nor our ability to identify dugongs with certainty, were affected by UAV altitude. Turbidity was the only environmental variable significantly affecting the dugong sighting rate. Our results suggest that UAV systems may not be limited by sea state conditions in the same manner as sightings from manned surveys. The overlap between images proved valuable for detecting animals that were masked by sun glitter in the corners of images, and identifying animals initially captured at awkward body angles. This initial trial of a basic camera system has successfully demonstrated that the ScanEagle UAV has great potential as a tool for marine mammal aerial surveys. PMID- 24223968 TI - Combinatorial engineering of 1-deoxy-D-xylulose 5-phosphate pathway using cross lapping in vitro assembly (CLIVA) method. AB - The ability to assemble multiple fragments of DNA into a plasmid in a single step is invaluable to studies in metabolic engineering and synthetic biology. Using phosphorothioate chemistry for high efficiency and site specific cleavage of sequences, a novel ligase independent cloning method (cross-lapping in vitro assembly, CLIVA) was systematically and rationally optimized in E. coli. A series of 16 constructs combinatorially expressing genes encoding enzymes in the 1-deoxy D-xylulose 5-phosphate (DXP) pathway were assembled using multiple DNA modules. A plasmid (21.6 kb) containing 16 pathway genes, was successfully assembled from 7 modules with high efficiency (2.0 x 10(3) cfu/ ug input DNA) within 2 days. Overexpressions of these constructs revealed the unanticipated inhibitory effects of certain combinations of genes on the production of amorphadiene. Interestingly, the inhibitory effects were correlated to the increase in the accumulation of intracellular methylerythritol cyclodiphosphate (MEC), an intermediate metabolite in the DXP pathway. The overexpression of the iron sulfur cluster operon was found to modestly increase the production of amorphadiene. This study demonstrated the utility of CLIVA in the assembly of multiple fragments of DNA into a plasmid which enabled the rapid exploration of biological pathways. PMID- 24223969 TI - Dynamic interplay between the periplasmic and transmembrane domains of GspL and GspM in the type II secretion system. AB - The type II secretion system (T2SS) is a multiprotein nanomachine that transports folded proteins across the outer membrane of gram-negative bacteria. The molecular mechanisms that govern the secretion process remain poorly understood. The inner membrane components GspC, GspL and GspM possess a single transmembrane segment (TMS) and a large periplasmic region and they are thought to form a platform of unknown function. Here, using two-hybrid and pull-down assays we performed a systematic mapping of the GspC/GspL/GspM interaction regions in the plant pathogen Dickeya dadantii. We found that the TMS of these components interact with each other, implying a complex interaction network within the inner membrane. We also showed that the periplasmic, ferredoxin-like, domains of GspL and GspM drive homo- and heterodimerizations of these proteins. Disulfide bonding analyses revealed that the respective domain interfaces include the equivalent secondary-structure elements, suggesting alternating interactions of the periplasmic domains, L/L and M/M versus L/M. Finally, we found that displacements of the periplasmic GspM domain mediate coordinated shifts or rotations of the cognate TMS. These data suggest a plausible mechanism for signal transmission between the periplasmic and the cytoplasmic portions of the T2SS machine. PMID- 24223970 TI - Inhibiting AKT phosphorylation employing non-cytotoxic anthraquinones ameliorates TH2 mediated allergic airways disease and rhinovirus exacerbation. AB - BACKGROUND: Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro. OBJECTIVE: To determine the anti-inflammatory potential of anthraquinones in-vivo. METHODS: BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation. RESULTS: Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung. CONCLUSION: Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. PMID- 24223971 TI - Glucose-6-phosphate dehydrogenase (G6PD)-deficient epithelial cells are less tolerant to infection by Staphylococcus aureus. AB - Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus alpha-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells. PMID- 24223972 TI - Influence of clonidine and ketamine on m-RNA expression in a model of opioid induced hyperalgesia in mice. AB - BACKGROUND: We investigated the influence of morphine and ketamine or clonidine in mice on the expression of genes that may mediate pronociceptive opioid effects. MATERIAL AND METHODS: C57BL/6 mice received morphine injections thrice daily using increasing doses (5-20 mg?kg(-1)) for 3 days (sub-acute, n=6) or 14 days (chronic, n=6) and additionally either s-ketamine (5 mg?kg(-1), n=6) or clonidine (0.1 mg?kg(-1), n=6). Tail flick test and the assessment of the mechanical withdrawal threshold of the hindpaw was performed during and 4 days after cessation of opioid treatment. Upon completion of the behavioural testing the mRNA-concentration of the NMDA receptor (NMDAR1) and beta-arrestin 2 (Arrb2) were measured by PCR. RESULTS: Chronic opioid treatment resulted in a delay of the tail flick latency with a rapid on- and offset. Simultaneously the mice developed a static mechanical hyperalgesia with a delayed onset that that outlasted the morphine treatment. Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Coadministration of s-ketamine or clonidine resulted in a reversal of the mechanical hyperalgesia and inhibited the normalization of NMDAR1 mRNA expression but had no effect on the expression of Arrb2 mRNA. CONCLUSION: In the model of chronic morphine therapy the antinociceptive effects of morphine are represented by the thermal analgesia while the proniceptive effects are represented by the mechanical hyperalgesia. The results indicate that the regulation of the expression of NMDAR1 and Arrb2 may be associated to the development of OIH in mice. PERSPECTIVE: The results indicate that co-administration of clonidine or ketamine may influence the underlying mechanisms of OIH. PMID- 24223973 TI - SWEETLEAD: an in silico database of approved drugs, regulated chemicals, and herbal isolates for computer-aided drug discovery. AB - In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database. The motivation for SWEETLEAD stems from the observance of conflicting information in publicly available chemical databases and the lack of a highly curated database of chemical structures for the globally approved drugs. A consensus building scheme surveying information from several publicly accessible databases was employed to identify the correct structure for each chemical. Resulting structures are filtered for the active pharmaceutical ingredient, standardized, and differing formulations of the same drug were combined in the final database. The publically available release of SWEETLEAD (https://simtk.org/home/sweetlead) provides an important tool to enable the successful completion of computer-aided repurposing and drug discovery campaigns. PMID- 24223974 TI - Donkey orchid symptomless virus: a viral 'platypus' from Australian terrestrial orchids. AB - Complete and partial genome sequences of two isolates of an unusual new plant virus, designated Donkey orchid symptomless virus (DOSV) were identified using a high-throughput sequencing approach. The virus was identified from asymptomatic plants of Australian terrestrial orchid Diuris longifolia (Common donkey orchid) growing in a remnant forest patch near Perth, western Australia. DOSV was identified from two D. longifolia plants of 264 tested, and from at least one plant of 129 Caladenia latifolia (pink fairy orchid) plants tested. Phylogenetic analysis of the genome revealed open reading frames (ORF) encoding seven putative proteins of apparently disparate origins. A 69-kDa protein (ORF1) that overlapped the replicase shared low identity with MPs of plant tymoviruses (Tymoviridae). A 157-kDa replicase (ORF2) and 22-kDa coat protein (ORF4) shared 32% and 40% amino acid identity, respectively, with homologous proteins encoded by members of the plant virus family Alphaflexiviridae. A 44-kDa protein (ORF3) shared low identity with myosin and an autophagy protein from Squirrelpox virus. A 27-kDa protein (ORF5) shared no identity with described proteins. A 14-kDa protein (ORF6) shared limited sequence identity (26%) over a limited region of the envelope glycoprotein precursor of mammal-infecting Crimea-Congo hemorrhagic fever virus (Bunyaviridae). The putative 25-kDa movement protein (MP) (ORF7) shared limited (27%) identity with 3A-like MPs of members of the plant-infecting Tombusviridae and Virgaviridae. Transmissibility was shown when DOSV systemically infected Nicotiana benthamiana plants. Structure and organization of the domains within the putative replicase of DOSV suggests a common evolutionary origin with 'potexvirus-like' replicases of viruses within the Alphaflexiviridae and Tymoviridae, and the CP appears to be ancestral to CPs of allexiviruses (Alphaflexiviridae). The MP shares an evolutionary history with MPs of dianthoviruses, but the other putative proteins are distant from plant viruses. DOSV is not readily classified in current lower order virus taxa. PMID- 24223975 TI - Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases. AB - In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2. PMID- 24223976 TI - Prominent heart organ-level performance deficits in a genetic model of targeted severe and progressive SERCA2 deficiency. AB - The cardiac SERCA2 Ca(2+) pump is critical for maintaining normal Ca(2+) handling in the heart. Reduced SERCA2a content and blunted Ca(2+) reuptake are frequently observed in failing hearts and evidence implicates poor cardiac Ca(2+) handling in the progression of heart failure. To gain insight into mechanism we investigated a novel genetic mouse model of inducible severe and progressive SERCA2 deficiency (inducible Serca2 knockout, SERCA2 KO). These mice eventually die from overt heart failure 7-10 weeks after knockout but as yet there have been no reports on intrinsic mechanical performance at the isolated whole heart organ level. Thus we studied whole-organ ex vivo function of hearts isolated from SERCA2 KO mice at one and four weeks post-knockout in adult animals. We found that isolated KO heart function was only modestly impaired one week post knockout, when SERCA2a protein was 32% of normal. At four weeks post-knockout, function was severely impaired with near non-detectable levels of SERCA2. During perfusion with 10 mM caffeine, LV developed pressures were similar between 4-week KO and control hearts, and end-diastolic pressures were lower in KO. When hearts were subjected to ischemia-reperfusion injury, recovery was not different between control and KO hearts at either one or four weeks post-knockout. Our findings indicate that ex vivo function of isolated SERCA2 KO hearts is severely impaired long before symptoms appear in vivo, suggesting that physiologically relevant heart function in vivo can be sustained for weeks in the absence of robust SR Ca(2+) flux. PMID- 24223977 TI - Early detection of poor adherers to statins: applying individualized surveillance to pay for performance. AB - BACKGROUND: Medication nonadherence costs $300 billion annually in the US. Medicare Advantage plans have a financial incentive to increase medication adherence among members because the Centers for Medicare and Medicaid Services (CMS) now awards substantive bonus payments to such plans, based in part on population adherence to chronic medications. We sought to build an individualized surveillance model that detects early which beneficiaries will fall below the CMS adherence threshold. METHODS: This was a retrospective study of over 210,000 beneficiaries initiating statins, in a database of private insurance claims, from 2008-2011. A logistic regression model was constructed to use statin adherence from initiation to day 90 to predict beneficiaries who would not meet the CMS measure of proportion of days covered 0.8 or above, from day 91 to 365. The model controlled for 15 additional characteristics. In a sensitivity analysis, we varied the number of days of adherence data used for prediction. RESULTS: Lower adherence in the first 90 days was the strongest predictor of one-year nonadherence, with an odds ratio of 25.0 (95% confidence interval 23.7-26.5) for poor adherence at one year. The model had an area under the receiver operating characteristic curve of 0.80. Sensitivity analysis revealed that predictions of comparable accuracy could be made only 40 days after statin initiation. When members with 30-day supplies for their first statin fill had predictions made at 40 days, and members with 90-day supplies for their first fill had predictions made at 100 days, poor adherence could be predicted with 86% positive predictive value. CONCLUSIONS: To preserve their Medicare Star ratings, plan managers should identify or develop effective programs to improve adherence. An individualized surveillance approach can be used to target members who would most benefit, recognizing the tradeoff between improved model performance over time and the advantage of earlier detection. PMID- 24223978 TI - Adherens junction distribution mechanisms during cell-cell contact elongation in Drosophila. AB - During Drosophila gastrulation, amnioserosa (AS) cells flatten and spread as an epithelial sheet. We used AS morphogenesis as a model to investigate how adherens junctions (AJs) distribute along elongating cell-cell contacts in vivo. As the contacts elongated, total AJ protein levels increased along their length. However, genetically blocking this AJ addition indicated that it was not essential for maintaining AJ continuity. Implicating other remodeling mechanisms, AJ photobleaching revealed non-directional lateral mobility of AJs along the elongating contacts, as well as local AJ removal from the membranes. Actin stabilization with jasplakinolide reduced AJ redistribution, and live imaging of myosin II along elongating contacts revealed fragmented, expanding and contracting actomyosin networks, suggesting a mechanism for lateral AJ mobility. Actin stabilization also increased total AJ levels, suggesting an inhibition of AJ removal. Implicating AJ removal by endocytosis, clathrin endocytic machinery accumulated at AJs. However, dynamin disruption had no apparent effect on AJs, suggesting the involvement of redundant or dynamin-independent mechanisms. Overall, we propose that new synthesis, lateral diffusion, and endocytosis play overlapping roles to populate elongating cell-cell contacts with evenly distributed AJs in this in vivo system. PMID- 24223979 TI - Water-limiting conditions alter the structure and biofilm-forming ability of bacterial multispecies communities in the alfalfa rhizosphere. AB - Biofilms are microbial communities that adhere to biotic or abiotic surfaces and are enclosed in a protective matrix of extracellular compounds. An important advantage of the biofilm lifestyle for soil bacteria (rhizobacteria) is protection against water deprivation (desiccation or osmotic effect). The rhizosphere is a crucial microhabitat for ecological, interactive, and agricultural production processes. The composition and functions of bacterial biofilms in soil microniches are poorly understood. We studied multibacterial communities established as biofilm-like structures in the rhizosphere of Medicago sativa (alfalfa) exposed to 3 experimental conditions of water limitation. The whole biofilm-forming ability (WBFA) for rhizospheric communities exposed to desiccation was higher than that of communities exposed to saline or nonstressful conditions. A culture-dependent ribotyping analysis indicated that communities exposed to desiccation or saline conditions were more diverse than those under the nonstressful condition. 16S rRNA gene sequencing of selected strains showed that the rhizospheric communities consisted primarily of members of the Actinobacteria and alpha- and gamma-Proteobacteria, regardless of the water limiting condition. Our findings contribute to improved understanding of the effects of environmental stress factors on plant-bacteria interaction processes and have potential application to agricultural management practices. PMID- 24223980 TI - Optimization of a pain model: effects of body temperature and anesthesia on bladder nociception in mice. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urological condition that is resistant to treatment and poorly understood. To determine novel molecular treatment targets and to elucidate the contribution of the nervous system to IC/BPS, many rodent bladder pain models have been developed. In this study we evaluated the effects of anesthesia induction and temperature variation in a mouse model of bladder pain known as urinary bladder distension (UBD). In this model compressed air is used to distend the bladder to distinct pressures while electrodes record the reflexive visceromotor response (VMR) from the overlying abdominal muscle. Two isoflurane induction models are commonly used before UBD: a short method lasting approximately 30 minutes and a long method lasting approximately 90 minutes. Animals were anesthetized with one of the methods then put through three sets of graded bladder distensions. Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used. In order to determine the effect of temperature on VMRs, animals were put through three graded distension sets at 37.5 (normal mouse body temperature), 35.5, and 33.5 degrees C. Distensions performed at 33.5 and 35.5 degrees C were significantly lower than those performed at 37.5 degrees C. Additionally, Western blot analysis revealed significantly smaller increases in spinal levels of phosphorylated extracellular signal regulated kinase 2 (pERK2) following bladder distension in animals whose body temperature was maintained at 33.5 degrees C as opposed to 37.5 degrees C. These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD. For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5 degrees C and isoflurane induction should gradually decrease over the course of 90 minutes. PMID- 24223981 TI - Heterologous expression of the wheat aquaporin gene TaTIP2;2 compromises the abiotic stress tolerance of Arabidopsis thaliana. AB - Aquaporins are channel proteins which transport water across cell membranes. We show that the bread wheat aquaporin gene TaTIP2;2 maps to the long arm of chromosome 7b and that its product localizes to the endomembrane system. The gene is expressed constitutively in both the root and the leaf, and is down-regulated by salinity and drought stress. Salinity stress induced an increased level of C methylation within the CNG trinucleotides in the TaTIP2;2 promoter region. The heterologous expression of TaTIP2;2 in Arabidopsis thaliana compromised its drought and salinity tolerance, suggesting that TaTIP2;2 may be a negative regulator of abiotic stress. The proline content of transgenic A. thaliana plants fell, consistent with the down-regulation of P5CS1, while the expression of SOS1, SOS2, SOS3, CBF3 and DREB2A, which are all stress tolerance-related genes acting in an ABA-independent fashion, was also down-regulated. The supply of exogenous ABA had little effect either on TaTIP2;2 expression in wheat or on the phenotype of transgenic A. thaliana. The expression level of the ABA signalling genes ABI1, ABI2 and ABF3 remained unaltered in the transgenic A. thaliana plants. Thus TaTIP2;2 probably regulates the response to stress via an ABA-independent pathway(s). PMID- 24223982 TI - Molecular markers reveal limited population genetic structure in a North American corvid, Clark's nutcracker (Nucifraga columbiana). AB - The genetic impact of barriers and Pleistocene glaciations on high latitude resident species has not been widely investigated. The Clark's nutcracker is an endemic North American corvid closely associated with Pinus-dominated forests. The nutcracker's encompasses known barriers to dispersal for other species, and glaciated and unglaciated areas. Clark's nutcrackers also irruptively disperse long distances in search of pine seed crops, creating the potential for gene flow among populations. Using the highly variable mitochondrial DNA control region, seven microsatellite loci, and species distribution modeling, we examined the effects of glaciations and dispersal barriers on population genetic patterns and population structure of nutcrackers. We sequenced 900 bp of mitochondrial control region for 169 individuals from 15 populations and analysed seven polymorphic microsatellite loci for 13 populations across the Clark's nutcracker range. We used species distribution modeling and a range of phylogeographic analyses to examine evolutionary history. Clark's nutcracker populations are not highly differentiated throughout their range, suggesting high levels of gene flow among populations, though we did find some evidence of isolation by distance and peripheral isolation. Our analyses suggested expansion from a single refugium after the last glacial maximum, but patterns of genetic diversity and paleodistribution modeling of suitable habitat were inconclusive as to the location of this refugium. Potential barriers to dispersal (e.g. mountain ranges) do not appear to restrict gene flow in Clark's nutcracker, and postglacial expansion likely occurred quickly from a single refugium located south of the ice sheets. PMID- 24223983 TI - Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1) viruses. AB - Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, alpha2 6 and alpha2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients. PMID- 24223984 TI - Development and validation of a clinical and computerised decision support system for management of hypertension (DSS-HTN) at a primary health care (PHC) setting. AB - BACKGROUND: Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective means to improve the management of hypertension at a primary health care (PHC) level in a developing country, nevertheless evidence on this regard is rather limited. METHODS: Development of DSS software was based on an algorithmic approach for (a) evaluation of a hypertensive patient, (b) risk stratification (c) drug management and (d) lifestyle interventions, based on Indian guidelines for hypertension II (2007). The beta testing of DSS software involved a feedback from the end users of the system on the contents of the user interface. Software validation and piloting was done in field, wherein the virtual recommendations and advice given by the DSS were compared with two independent experts (government doctors from the non-participating PHC centers). RESULTS: The overall percent agreement between the DSS and independent experts among 60 hypertensives on drug management was 85% (95% CI: 83.61-85.25). The kappa statistic for overall agreement for drug management was 0.659 (95% CI: 0.457-0.862) indicating a substantial degree of agreement beyond chance at an alpha fixed at 0.05 with 80% power. Receiver operator curve (ROC) showed a good accuracy for the DSS, wherein, the area under curve (AUC) was 0.848 (95% CI: 0.741-0.948). Sensitivity and specificity of the DSS were 83.33 and 85.71% respectively when compared with independent experts. CONCLUSION: A point of care, pilot tested and validated DSS for management of hypertension has been developed in a resource constrained low and middle income setting and could contribute to improved management of hypertension at a primary health care level. PMID- 24223985 TI - Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people. AB - BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease. PMID- 24223986 TI - A combination of Let-7d, Let-7g and Let-7i serves as a stable reference for normalization of serum microRNAs. AB - Recent studies have indicated that circulating microRNAs (miRNAs) in serum and plasma are stable and can serve as biomarkers of many human diseases. Measurement of circulating miRNAs with sufficient sensitivity and precision, however, faces some special challenges, among which proper normalization is the most critical but often an underappreciated issue. The primary aim of this study was to identify endogenous reference genes that maintain consistent levels under various conditions to serve as an internal control for quantification of serum miRNAs. We developed a strategy combining Illumina's sequencing by synthesis (SBS) technology, reverse transcription quantitative polymerase chain reaction (RT qPCR) assay, literature screening and statistical analysis to screen and validate the most suitable reference genes. A combination of let-7d, let-7g and let-7i is selected as a reference for the normalization of serum miRNAs and it is statistically superior to the commonly used reference genes U6, RNU44, RNU48 and miR-16. This has important implications for proper experimental design and accurate data interpretation. PMID- 24223987 TI - Matrix metalloproteases and tissue inhibitors of metalloproteinases in medial plica and pannus-like tissue contribute to knee osteoarthritis progression. AB - Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP 9, IL-1beta, and TNF-alpha mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1beta, while plica cell migration was enhanced by TNF-alpha. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee. PMID- 24223988 TI - Bayesian phylogeography of Crimean-Congo hemorrhagic fever virus in Europe. AB - Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10(-4) (95%HPD=1.6 and 4.7 x 10(-4)) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe. PMID- 24223989 TI - Enhanced methanol production in plants provides broad spectrum insect resistance. AB - Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants. PMID- 24223990 TI - Diversity of both the cultivable protease-producing bacteria and bacterial extracellular proteases in the coastal sediments of King George Island, Antarctica. AB - Protease-producing bacteria play a vital role in degrading sedimentary organic nitrogen. However, the diversity of these bacteria and their extracellular proteases in most regions remain unknown. In this paper, the diversity of the cultivable protease-producing bacteria and of bacterial extracellular proteases in the sediments of Maxwell Bay, King George Island, Antarctica was investigated. The cultivable protease-producing bacteria reached 10(5) cells/g in all 8 sediment samples. The cultivated protease-producing bacteria were mainly affiliated with the phyla Actinobacteria, Firmicutes, Bacteroidetes, and Proteobacteria, and the predominant genera were Bacillus (22.9%), Flavobacterium (21.0%) and Lacinutrix (16.2%). Among these strains, Pseudoalteromonas and Flavobacteria showed relatively high protease production. Inhibitor analysis showed that nearly all the extracellular proteases from the bacteria were serine proteases or metalloproteases. These results begin to address the diversity of protease-producing bacteria and bacterial extracellular proteases in the sediments of the Antarctic Sea. PMID- 24223991 TI - The scavenger protein apoptosis inhibitor of macrophages (AIM) potentiates the antimicrobial response against Mycobacterium tuberculosis by enhancing autophagy. AB - Apoptosis inhibitor of macrophages (AIM), a scavenger protein secreted by tissue macrophages, is transcriptionally regulated by the nuclear receptor Liver X Receptor (LXR) and Retinoid X Receptor (RXR) heterodimer. Given that LXR exerts a protective immune response against M. tuberculosis, here we analyzed whether AIM is involved in this response. In an experimental murine model of tuberculosis, AIM serum levels peaked dramatically early after infection with M. tuberculosis, providing an in vivo biological link to the disease. We therefore studied the participation of AIM in macrophage response to M. tuberculosis in vitro. For this purpose, we used the H37Rv strain to infect THP-1 macrophages transfected to stably express AIM, thereby increasing infected macrophage survival. Furthermore, the expression of this protein enlarged foam cell formation by enhancing intracellular lipid content. Phagocytosis assays with FITC-labeled M. tuberculosis bacilli indicated that this protein was not involved in bacterial uptake; however, AIM expression decreased the number of intracellular cfus by up to 70% in bacterial killing assays, suggesting that AIM enhances macrophage mycobactericidal activity. Accordingly, M. tuberculosis-infected AIM-expressing cells upregulated the production of reactive oxygen species. Moreover, real-time PCR analysis showed increased mRNA levels of the antimicrobial peptides cathelicidin and defensin 4B. These increases were concomitant with greater cellular concentrations of the autophagy-related molecules Beclin 1 and LC3II, as well as enhanced acidification of mycobacterial phagosomes and LC3 co localization. In summary, our data support the notion that AIM contributes to key macrophage responses to M. tuberculosis. PMID- 24223993 TI - N-cadherin relocalizes from the periphery to the center of the synapse after transient synaptic stimulation in hippocampal neurons. AB - N-cadherin is a cell adhesion molecule which is enriched at synapses. Binding of N-cadherin molecules to each other across the synaptic cleft has been postulated to stabilize adhesion between the presynaptic bouton and the postsynaptic terminal. N-cadherin is also required for activity-induced changes at synapses, including hippocampal long term potentiation and activity-induced spine expansion and stabilization. We hypothesized that these activity-dependent changes might involve changes in N-cadherin localization within synapses. To determine whether synaptic activity changes the localization of N-cadherin, we used structured illumination microscopy, a super-resolution approach which overcomes the conventional resolution limits of light microscopy, to visualize the localization of N-cadherin within synapses of hippocampal neurons. We found that synaptic N cadherin exhibits a spectrum of localization patterns, ranging from puncta at the periphery of the synapse adjacent to the active zone to an even distribution along the synaptic cleft. Furthermore, the N-cadherin localization pattern within synapses changes during KCl depolarization and after transient synaptic stimulation. During KCl depolarization, N-cadherin relocalizes away from the central region of the synaptic cleft to the periphery of the synapse. In contrast, after transient synaptic stimulation with KCl followed by a period of rest in normal media, fewer synapses have N-cadherin present as puncta at the periphery and more synapses have N-cadherin present more centrally and uniformly along the synapse compared to unstimulated cells. This indicates that transient synaptic stimulation modulates N-cadherin localization within the synapse. These results bring new information to the structural organization and activity-induced changes occurring at synapses, and suggest that N-cadherin relocalization may contribute to activity dependent changes at synapses. PMID- 24223992 TI - Retinoic acid improves morphology of cultured peritoneal mesothelial cells from patients undergoing dialysis. AB - Patients undergoing continuous ambulatory peritoneal dialysis are classified according to their peritoneal permeability as low transporter (low solute permeability) or High transporter (high solute permeability). Factors that determine the differences in permeability between them have not been fully disclosed. We investigated morphological features of cultured human peritoneal mesothelial cells from low or high transporter patients and its response to All trans retinoic Acid (ATRA, vitamin A active metabolite), as compared to non uremic human peritoneal mesothelial cells. Control cells were isolated from human omentum. High or low transporter cells were obtained from dialysis effluents. Cells were cultured in media containing ATRA (0, 50, 100 or 200 nM). We studied length and distribution of microvilli and cilia (scanning electron microscopy), epithelial (cytokeratin, claudin-1, ZO-1 and occludin) and mesenchymal (vimentin and alpha-smooth muscle actin) transition markers by immunofluorescence and Western blot, and transforming growth factor beta1 expression by Western blot. Low and high transporter exhibited hypertrophic cells, reduction in claudin-1, occludin and ZO-1 expression, cytokeratin and vimentin disorganization and positive alpha-smooth muscle actin label. Vimentin, alpha-smooth muscle actin and transforming growth factor-beta1 were overexpressed in low transporter. Ciliated cells were diminished in low and high transporters. Microvilli number and length were severely reduced in high transporter. ATRA reduced hypertrophic cells number in low transporter. It also improved cytokeratin and vimentin organization, decreased vimentin and alpha-smooth muscle actin expression, and increased claudin 1, occludin and ZO-1 expression, in low and high transporter. In low transporter, ATRA reduced transforming growth factor-beta1 expression. ATRA augmented percentage of ciliated cells in low and high transporter. It also augmented cilia length in high transporter. Alterations in structure, epithelial mesenchymal markers and transforming growth factor-beta1 expression were differential between low and high transporter. Beneficial effects of ATRA were improved human peritoneal mesothelial cells morphology tending to normalize structures. PMID- 24223994 TI - Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers. AB - Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) -with no leg ulcers at the time of the study--were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role. PMID- 24223995 TI - Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis. AB - A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti muscle wasting. PMID- 24223996 TI - GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70. AB - The use of exocytosis for membrane expansion at nerve growth cones is critical for neurite outgrowth. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking to the plasma membrane. Recent studies have shown that TC10 and its effector Exo70, a component of the exocyst tethering complex, contribute to neurite outgrowth. However, the molecular mechanisms of the neuritogenesis-promoting functions of TC10 remain to be established. Here, we propose that GTP hydrolysis of vesicular TC10 near the plasma membrane promotes neurite outgrowth by accelerating vesicle fusion by releasing Exo70. Using Forster resonance energy transfer (FRET)-based biosensors, we show that TC10 activity at the plasma membrane decreased at extending growth cones in hippocampal neurons and nerve growth factor (NGF)-treated PC12 cells. In neuronal cells, TC10 activity at vesicles was higher than its activity at the plasma membrane, and TC10-positive vesicles were found to fuse to the plasma membrane in NGF-treated PC12 cells. Therefore, activity of TC10 at vesicles is presumed to be inactivated near the plasma membrane during neuronal exocytosis. Our model is supported by functional evidence that constitutively active TC10 could not rescue decrease in NGF-induced neurite outgrowth induced by TC10 depletion. Furthermore, TC10 knockdown experiments and colocalization analyses confirmed the involvement of Exo70 in TC10-mediated trafficking in neuronal cells. TC10 frequently resided on vesicles containing Rab11, which is a key regulator of recycling pathways and implicated in neurite outgrowth. In growth cones, most of the vesicles containing the cell adhesion molecule L1 had TC10. Exocytosis of Rab11- and L1-positive vesicles may play a central role in TC10-mediated neurite outgrowth. The combination of this study and our previous work on the role of TC10 in EGF induced exocytosis in HeLa cells suggests that the signaling machinery containing TC10 proposed here may be broadly used for exocytosis. PMID- 24223997 TI - Global transcriptome analysis of Lactococcus garvieae strains in response to temperature. AB - Lactococcus garvieae is an important fish and an opportunistic human pathogen. The genomic sequences of several L. garvieae strains have been recently published, opening the possibility of global studies on the biology of this pathogen. In this study, a whole genome DNA microarray of two strains of L. garvieae was designed and validated. This DNA microarray was used to investigate the effects of growth temperature (18 degrees C and 37 degrees C) on the transcriptome of two clinical strains of L. garvieae that were isolated from fish (Lg8831) and from a human case of septicemia (Lg21881). The transcriptome profiles evidenced a strain-specific response to temperature, which was more evident at 18 degrees C. Among the most significant findings, Lg8831 was found to up-regulate at 18 degrees C several genes encoding different cold-shock and cold induced proteins involved in an efficient adaptive response of this strain to low temperature conditions. Another relevant result was the description, for the first time, of respiratory metabolism in L. garvieae, whose gene expression regulation was temperature-dependent in Lg21881. This study provides new insights about how environmental factors such as temperature can affect L. garvieae gene expression. These data could improve our understanding of the regulatory networks and adaptive biology of this important pathogen. PMID- 24223998 TI - Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells. AB - Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin 4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively. PMID- 24223999 TI - Effects of news frames on perceived risk, emotions, and learning. AB - The media play a key role in forming opinions by influencing people's understanding and perception of a topic. People gather information about topics of interest from the internet and print media, which employ various news frames to attract attention. One example of a common news frame is the human-interest frame, which emotionalizes and dramatizes information and often accentuates individual affectedness. Our study investigated effects of human-interest frames compared to a neutral-text condition with respect to perceived risk, emotions, and knowledge acquisition, and tested whether these effects can be "generalized" to common variants of the human-interest frame. Ninety-one participants read either one variant of the human-interest frame or a neutrally formulated version of a newspaper article describing the effects of invasive species in general and the Asian ladybug (an invasive species) in particular. The framing was achieved by varying the opening and concluding paragraphs (about invasive species), as well as the headline. The core text (about the Asian ladybug) was the same across all conditions. All outcome variables on framing effects referred to this common core text. We found that all versions of the human-interest frame increased perceived risk and the strength of negative emotions compared to the neutral text. Furthermore, participants in the human-interest frame condition displayed better (quantitative) learning outcomes but also biased knowledge, highlighting a potential dilemma: Human-interest frames may increase learning, but they also lead to a rather unbalanced view of the given topic on a "deeper level". PMID- 24224000 TI - Plasma peptide biomarker discovery for amyotrophic lateral sclerosis by MALDI-TOF mass spectrometry profiling. AB - The diagnostic of Amyotrophic lateral sclerosis (ALS) remains based on clinical and neurophysiological observations. The actual delay between the onset of the symptoms and diagnosis is about 1 year, preventing early inclusion of patients into clinical trials and early care of the disease. Therefore, finding biomarkers with high sensitivity and specificity remains urgent. In our study, we looked for peptide biomarkers in plasma samples using reverse phase magnetic beads (C18 and C8) and MALDI-TOF mass spectrometry analysis. From a set of ALS patients (n=30) and healthy age-matched controls (n=30), C18- or C8-SVM-based models for ALS diagnostic were constructed on the base of the minimum of the most discriminant peaks. These two SVM-based models end up in excellent separations between the 2 groups of patients (recognition capability overall classes > 97%) and classify blinded samples (10 ALS and 10 healthy age-matched controls) with very high sensitivities and specificities (>90%). Some of these discriminant peaks have been identified by Mass Spectrometry (MS) analyses and correspond to (or are fragments of) major plasma proteins, partly linked to the blood coagulation. PMID- 24224001 TI - Relationship between the COMT-Val158Met and BDNF-Val66Met polymorphisms, childhood trauma and psychotic experiences in an adolescent general population sample. AB - OBJECTIVE: Psychotic experiences occur at a much greater prevalence in the population than psychotic disorders. There has been little research to date, however, on genetic risk for this extended psychosis phenotype. We examined whether COMT or BDNF genotypes were associated with psychotic experiences or interacted with childhood trauma in predicting psychotic experiences. METHOD: Psychiatric interviews and genotyping for COMT-Val158Met and BDNF-Val66Met were carried out on two population-based samples of 237 individuals aged 11-15 years. Logistic regression was used to examine for main effects by genotype and childhood trauma, controlling for important covariates. This was then compared to a model with a term for interaction between genotype and childhood trauma. Where a possible interaction was detected, this was further explored in stratified analyses. RESULTS: While childhood trauma showed a borderline association with psychotic experiences, COMT-Val158Met and BDNF-Val66Met genotypes were not directly associated with psychotic experiences in the population. Testing for gene x environment interaction was borderline significant in the case of COMT Val158Met with individuals with the COMT-Val158Met Val-Val genotype, who had been exposed to childhood trauma borderline significantly more likely to report psychotic experiences than those with Val-Met or Met-Met genotypes. There was no similar interaction by BDNF-Val66Met genotype. CONCLUSION: The COMT-Val158Met Val Val genotype may be a genetic moderator of risk for psychotic experiences in individuals exposed to childhood traumatic experiences. PMID- 24224002 TI - Activity of Bdellovibrio hit locus proteins, Bd0108 and Bd0109, links Type IVa pilus extrusion/retraction status to prey-independent growth signalling. AB - Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction) locus on the Bdellovibrio genome were associated with the transition to prey-independent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall), and that the presence (and possibly retraction state) of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation backgrounds. PMID- 24224003 TI - Radiotherapy after radical prostatectomy: treatment recommendations differ between urologists and radiation oncologists. AB - PURPOSE: There is no consensus on optimal use of radiotherapy following radical prostatectomy. The purpose of this study was to describe opinions of urologists and radiation oncologists regarding adjuvant and salvage radiotherapy following radical prostatectomy. METHODS: Urologists and genitourinary radiation oncologists were solicited to participate in an online survey. Respondent characteristics included demographics, training, practice setting, patient volume/experience, and access to radiotherapy. Participant practice patterns and attitudes towards use of adjuvant and salvage radiotherapy in standardized clinical scenarios were assessed. RESULTS: One hundred and forty-six staff physicians participated in the survey (104 urologists and 42 genitourinary radiation oncologists). Overall, high Gleason score (Gleason 7 vs. 6, RR 1.37 95% CI 1.19-1.56, p<0.0001 and Gleason 8-10 vs. 6, RR 1.56 95% CI 1.37-1.78, p<0.0001), positive surgical margin (RR 1.43 95% CI 1.26-1.62, p<0.0001), and extraprostatic tumour extension (RR 1.16 95% CI 1.05-1.28, p<0.002) conferred an increased probability of recommending adjuvant radiotherapy. Radiation oncologists were more likely to recommend adjuvant radiotherapy across all clinical scenarios (RR 1.48, 95% CI 1.39, 1.60, p <0.001). Major differences were found for patients with Gleason 6 and isolated positive surgical margin (radiotherapy selected by 21% of urologists vs. 70% of radiation oncologists), and patients with extraprostatic extension and negative surgical margins (radiotherapy selected by 18% of urologist vs. 57% of radiation oncologists). CONCLUSIONS: Urologists and radiation oncologists frequently disagree about recommendation for post-prostatectomy adjuvant radiotherapy. Since clinical equipoise exists between adjuvant versus early salvage post-operative radiotherapy, support of clinical trials comparing these approaches is strongly encouraged. PMID- 24224004 TI - Tumor stiffness is unrelated to myosin light chain phosphorylation in cancer cells. AB - Many tumors are stiffer than their surrounding tissue. This increase in stiffness has been attributed, in part, to a Rho-dependent elevation of myosin II light chain phosphorylation. To characterize this mechanism further, we studied myosin light chain kinase (MLCK), the main enzyme that phosphorylates myosin II light chains. We anticipated that increases in MLCK expression and activity would contribute to the increased stiffness of cancer cells. However, we find that MLCK mRNA and protein levels are substantially less in cancer cells and tissues than in normal cells. Consistent with this observation, cancer cells contract 3D collagen matrices much more slowly than normal cells. Interestingly, inhibiting MLCK or Rho kinase did not affect the 3D gel contractions while blebbistatin partially and cytochalasin D maximally inhibited contractions. Live cell imaging of cells in collagen gels showed that cytochalasin D inhibited filopodia-like projections that formed between cells while a MLCK inhibitor had no effect on these projections. These data suggest that myosin II phosphorylation is dispensable in regulating the mechanical properties of tumors. PMID- 24224005 TI - Novel disulfide bond-mediated dimerization of the CARD domain was revealed by the crystal structure of CARMA1 CARD. AB - CARMA1, BCL10 and MALT1 form a large molecular complex known as the CARMA1 signalosome during lymphocyte activation. Lymphocyte activation via the CARMA1 signalosome is critical to immune response and linked to many immune diseases. Despite the important role of the CARMA1 signalosome during lymphocyte activation and proliferation, limited structural information is available. Here, we report the dimeric structure of CARMA1 CARD at a resolution of 3.2 A. Interestingly, although CARMA1 CARD has a canonical six helical-bundles structural fold similar to other CARDs, CARMA1 CARD shows the first homo-dimeric structure of CARD formed by a disulfide bond and reveals a possible biologically important homo dimerization mechanism. PMID- 24224007 TI - What time periods of the day are concerning for parents of children with attention deficit hyperactivity disorder? AB - BACKGROUND/AIM: The questionnaire-children with difficulties (QCD) is a parent assessed questionnaire designed to evaluate a child's difficulties in functioning during specific time periods of the day. In this study, the QCD was applied to determine the time periods of the day that are concerning for the parents of children with attention deficit hyperactivity disorder (ADHD). The results were compared with those for a community sample. METHODS: Elementary and junior high school students with ADHD (243 boys, 55 girls) and a community sample of children (518 boys, 618 girls) were enrolled in this study. Their behaviors were assessed by the QCD, the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI). The effects of gender (boy/girl) and diagnosis (ADHD/community sample) on the total QCD score were analyzed across each school grade (elementary/junior high school). Correlation coefficients between QCD and ADHD-RS/ODBI scores were analyzed. RESULTS: The QCD score for the ADHD group was significantly lower than that for the community sample (P < 0.001). There were significantly strong correlations between "evening" and ADHD-RS and ODBI scores for all children with ADHD (r > 0.41, P < 0.001) and between "night" and inattention and oppositional symptoms for the girls with ADHD (r > 0.40, P < 0.001). CONCLUSIONS: Parents reported that children with ADHD faced greater difficulties in completing basic daily activities compared with the community controls, particularly in the evening. Furthermore, these difficulties were related to the severity of ADHD symptoms. The parents' perceptions depended on the gender, ADHD and oppositional symptoms, and the time period of the day. This study determined that children with ADHD face greater difficulties in daily functioning compared with community sample children, that these difficulties are time-dependent, and that these difficulties were particularly experienced in the evening. PMID- 24224006 TI - Expressed sequence tags for bovine muscle satellite cells, myotube formed-cells and adipocyte-like cells. AB - BACKGROUND: Muscle satellite cells (MSCs) represent a devoted stem cell population that is responsible for postnatal muscle growth and skeletal muscle regeneration. An important characteristic of MSCs is that they encompass multi potential mesenchymal stem cell activity and are able to differentiate into myocytes and adipocytes. To achieve a global view of the genes differentially expressed in MSCs, myotube formed-cells (MFCs) and adipocyte-like cells (ALCs), we performed large-scale EST sequencing of normalized cDNA libraries developed from bovine MSCs. RESULTS: A total of 24,192 clones were assembled into 3,333 clusters, 5,517 singletons and 3,842contigs. Functional annotation of these unigenes revealed that a large portion of the differentially expressed genes are involved in cellular and signaling processes. Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis of three subsets of highly expressed gene lists (MSC233, MFC258, and ALC248) highlighted some common and unique biological processes among MSC, MFC and ALC. Additionally, genes that may be specific to MSC, MFC and ALC are reported here, and the role of dimethylarginine dimethylaminohydrolase2 (DDAH2) during myogenesis and hemoglobin subunit alpha2 (HBA2) during transdifferentiation in C2C12 were assayed as a case study. DDAH2 was up-regulated during myognesis and knockdown of DDAH2 by siRNA significantly decreased myogenin (MYOG) expression corresponding with the slight change in cell morphology. In contrast, HBA2 was up-regulated during ALC formation and resulted in decreased intracellular lipid accumulation and CD36 mRNA expression upon knockdown assay. CONCLUSION: In this study, a large number of EST sequences were generated from the MSC, MFC and ALC. Overall, the collection of ESTs generated in this study provides a starting point for the identification of novel genes involved in MFC and ALC formation, which in turn offers a fundamental resource to enable better understanding of the mechanism of muscle differentiation and transdifferentiation. PMID- 24224008 TI - Population structure and genetic diversity of native and invasive populations of Solanum rostratum (Solanaceae). AB - AIMS: We investigate native and introduced populations of Solanum rostratum, an annual, self-compatible plant that has been introduced around the globe. This study is the first to compare the genetic diversity of Solanum rostratum between native and introduced populations. We aim to (1) determine the level of genetic diversity across the studied regions; (2) explore the likely origins of invasive populations in China; and (3) investigate whether there is the evidence of multiple introductions into China. METHODS: We genotyped 329 individuals at 10 microsatellite loci to determine the levels of genetic diversity and to investigate population structure of native and introduced populations of S. rostratum. We studied five populations in each of three regions across two continents: Mexico, the U.S.A. and China. IMPORTANT FINDINGS: We found the highest genetic diversity among Mexican populations of S. rostratum. Genetic diversity was significantly lower in Chinese and U.S.A. populations, but we found no regional difference in inbreeding coefficients (F IS) or population differentiation (F ST). Population structure analyses indicate that Chinese and U.S.A. populations are more closely related to each other than to sampled Mexican populations, revealing that introduced populations in China share an origin with the sampled U.S.A. populations. The distinctiveness between some introduced populations indicates multiple introductions of S. rostratum into China. PMID- 24224009 TI - Novel mutations of ABCB6 associated with autosomal dominant dyschromatosis universalis hereditaria. AB - OBJECTIVE: Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH. METHODS: Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically matched normal Chinese individuals. RESULTS: Histopathological analysis showed melanocytes in normal control's skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6. CONCLUSION: Our data add new variants to the repertoire of ABCB6 mutations with DUH. PMID- 24224010 TI - Time trends and inequalities of under-five mortality in Nepal: a secondary data analysis of four demographic and health surveys between 1996 and 2011. AB - BACKGROUND: Inequalities in progress towards achievement of Millennium Development Goal four (MDG-4) reflect unequal access to child health services. OBJECTIVE: To examine the time trends, socio-economic and regional inequalities of under-five mortality rate (U5MR) in Nepal. METHODS: We analyzed the data from complete birth histories of four Nepal Demographic and Health Surveys (NDHS) done in the years 1996, 2001, 2006 and 2011. For each livebirth, we computed survival period from birth until either fifth birthday or the survey date. Using direct methods i.e. by constructing life tables, we calculated yearly U5MRs from 1991 to 2010. Projections were made for the years 2011 to 2015. For each NDHS, U5MRs were calculated according to child's sex, mother's education, household wealth index, rural/urban residence, development regions and ecological zones. Inequalities were calculated as rate difference, rate ratio, population attributable risk and hazard ratio. RESULTS: Yearly U5MR (per 1000 live births) had decreased from 157.3 (95% CIs 178.0-138.9) in 1991 to 43.2 (95% CIs 59.1-31.5) in 2010 i.e. 114.1 reduction in absolute risk. Projected U5MR for the year 2015 was 54.33. U5MRs had decreased in absolute terms in all sub groups but relative inequalities had reduced for gender and rural/urban residence only. Wide inequalities existed by wealth and education and increased between 1996 and 2011. For lowest wealth quintile (as compared to highest quintile) hazard ratio (HR) increased from 1.37 (95% CIs 1.27, 1.49) to 2.54 ( 95% CIs 2.25, 2.86) and for mothers having no education (as compared to higher education) HR increased from 2.55 (95% CIs 1.95, 3.33) to 3.75 (95% CIs 3.17, 4.44). Changes in regional inequities were marginal and irregular. CONCLUSIONS: Nepal is most likely to achieve MDG-4 but eductional and wealth inequalities may widen further. National health policies should address to reduce inequalities in U5MR through 'inclusive policies'. PMID- 24224011 TI - Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue. AB - AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD), regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting). METHODS AND RESULTS: Male C57BL/6 (WT) and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase) and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36) and Fatty acid transport protein (FATP) 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar) alpha signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK) phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARalpha-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation. PMID- 24224012 TI - Elevated Klotho promoter methylation is associated with severity of chronic kidney disease. AB - Klotho (KL) expression is down-regulated in the renal tissues of chronic kidney disease (CKD) animal models and patients with end-stage renal disease. The putative role of KL promoter hypermethylation in the progression of CKD remains unclear. The present study aimed to determine renal and peripheral blood mononuclear cells (PBMC) levels of KL promoter methylation and analyze their relationship with clinical and histological severity in patients with CKD. Using bisulfite pyrosequencing, renal and PBMC levels of KL promoter methylation were quantified in 47 patients with CKD. 47 nephrectomy specimens of patients with renal cell carcinoma and 48 PBMC specimens of healthy volunteers were used as renal tissue and PBMC controls, respectively. Renal expression of KL protein was assayed by immunohistochemistry staining. Receiver operating characteristic (ROC) curve was used to identify the optimal cut-off value of PBMC KL promoter methylation level for renal KL promoter hypermethylation. Higher levels of KL promoter methylation were observed in renal tissue and PBMC in patients with CKD compared with controls (8.79+/-3.24 vs. 5.17+/-1.11%, P<0.001; 7.20+/-2.79 vs. 3.27+/-0.79%, P<0.001). In these patients, renal KL methylation level correlated inversely with renal KL immunostaining intensity (rho=-0.794, P<0.001). Estimated glomerular filtration rate correlated inversely with renal and PBMC levels of KL promoter methylation (r=-0.829, P<0.001; r=-0.645, P<0.001), while tubulointerstistial fibrosis score correlated positively (rho=0.826, P<0.001; rho=0.755, P<0.001). PBMC KL promoter methylation level correlated positively with renal KL promoter methylation level in patients with CKD (r=0.787, P<0.001). In ROC curve, the area under curve was 0.964 (P<0.001) and the optimal cut-off value was 5.83% with a sensitivity of 93.8% and specificity of 86.7% to predict renal KL promoter hypermethylation. The degree of KL promoter methylation is associated with clinical and histological severity of CKD. PBMC KL promoter methylation level may act as a potential biomarker of renal KL promoter hypermethylation. PMID- 24224013 TI - Functional role of Mst1/Mst2 in embryonic stem cell differentiation. AB - The Hippo pathway is an evolutionary conserved pathway that involves cell proliferation, differentiation, apoptosis and organ size regulation. Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in controlling embryonic stem cells (ES cells) has yet to be exploited. To further understand the Mst1/Mst2 function in ES cell pluripotency and differentiation, we derived Mst1/Mst2 double knockout (Mst-/-) ES cells to completely perturb Hippo signaling. We found that Mst-/- ES cells express higher level of Nanog than wild type ES cells and show differentiation resistance after LIF withdrawal. They also proliferate faster than wild type ES cells. Although Mst-/- ES cells can form embryoid bodies (EBs), their differentiation into tissues of three germ layers is distorted. Intriguingly, Mst /- ES cells are unable to form teratoma. Mst-/- ES cells can differentiate into mesoderm lineage, but further differentiation to cardiac lineage cells is significantly affected. Microarray analysis revealed that ligands of non canonical Wnt signaling, which is critical for cardiac progenitor specification, are significantly repressed in Mst-/- EBs. Taken together our results showed that Mst1/Mst2 are required for proper cardiac lineage cell development and teratoma formation. PMID- 24224014 TI - In vitro and in vivo characterization of ultraviolet light C-irradiated human platelets in a 2 event mouse model of transfusion. AB - UV-based pathogen reduction technologies have been developed in recent years to inactivate pathogens and contaminating leukocytes in platelet transfusion products in order to prevent transfusion-transmitted infections and alloimmunization. UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers. Previously, it was reported that UVC irradiation induces platelet aggregation and activation. To understand if UVC-induced changes of platelet quality correlate with potential adverse events when these platelets are transfused into animals, we used a 2-event SCID mouse model in which the predisposing event was LPS treatment and the second event was infusion of UVC irradiated platelets. We analyzed lung platelet accumulation, protein content in bronchoalveolar lavage fluid as an indication of lung injury, and macrophage inflammatory protein-2 (MIP-2) release in mice received UVC-irradiated or untreated control platelets. Our results showed UVC-irradiated platelets accumulated in lungs of the mice in a dose-dependent manner. High-doses of UVC irradiated platelets were sequestered in the lungs to a similar level as we previously reported for UVB-irradiated platelets. Unlike UVB-platelets, UVC platelets did not lead to lung injury or induce MIP-2 release. This could potentially be explained by our observation that although UVC treatment activated platelet surface alphaIIbbeta3, it failed to activate platelet cells. It also suggests lung platelet accumulation and subsequent lung damage are due to different and separate mechanisms which require further investigation. PMID- 24224015 TI - Repression and recuperation of brood production in Bombus terrestris bumble bees exposed to a pulse of the neonicotinoid pesticide imidacloprid. AB - Currently, there is concern about declining bee populations and some blame the residues of neonicotinoid pesticides in the nectar and pollen of treated crops. Bumble bees are important wild pollinators that are widely exposed to dietary neonicotinoids by foraging in agricultural environments. In the laboratory, we tested the effect of a pulsed exposure (14 days 'on dose' followed by 14 days 'off dose') to a common neonicotinoid, imidacloprid, on the amount of brood (number of eggs and larvae) produced by Bombus terrestris L. bumble bees in small, standardised experimental colonies (a queen and four adult workers). During the initial 'on dose' period we observed a dose-dependent repression of brood production in colonies, with productivity decreasing as dosage increased up to 98 ug kg(-1) dietary imidacloprid. During the following 'off dose' period, colonies showed a dose-dependent recuperation such that total brood production during the 28-day pulsed exposure was not correlated with imidacloprid up to 98 ug kg(-1). Our findings raise further concern about the threat to wild bumble bees from neonicotinoids, but they also indicate some resilience to a pulsed exposure, such as that arising from the transient bloom of a treated mass flowering crop. PMID- 24224016 TI - A RhoC biosensor reveals differences in the activation kinetics of RhoA and RhoC in migrating cells. AB - RhoA and RhoC GTPases share 92% amino acid sequence identity, yet play different roles in regulating cell motility and morphology. To understand these differences, we developed and validated a biosensor of RhoC activation (RhoC FLARE). This was used together with a RhoA biosensor to compare the spatio temporal dynamics of RhoA and RhoC activity during cell protrusion/retraction and macropinocytosis. Both GTPases were activated similarly at the cell edge, but in regions more distal from the edge RhoC showed higher activation during protrusion. The two isoforms differed markedly in the kinetics of activation. RhoC was activated concomitantly with RhoA at the cell edge, but distally, RhoC activation preceded RhoA activation, occurring before edge protrusion. During macropinocytosis, differences were observed during vesicle closure and in the area surrounding vesicle formation. PMID- 24224017 TI - ConfocalCheck--a software tool for the automated monitoring of confocal microscope performance. AB - Laser scanning confocal microscopy has become an invaluable tool in biomedical research but regular quality testing is vital to maintain the system's performance for diagnostic and research purposes. Although many methods have been devised over the years to characterise specific aspects of a confocal microscope like measuring the optical point spread function or the field illumination, only very few analysis tools are available. Our aim was to develop a comprehensive quality assurance framework ranging from image acquisition to automated analysis and documentation. We created standardised test data to assess the performance of the lasers, the objective lenses and other key components required for optimum confocal operation. The ConfocalCheck software presented here analyses the data fully automatically. It creates numerous visual outputs indicating potential issues requiring further investigation. By storing results in a web browser compatible file format the software greatly simplifies record keeping allowing the operator to quickly compare old and new data and to spot developing trends. We demonstrate that the systematic monitoring of confocal performance is essential in a core facility environment and how the quantitative measurements obtained can be used for the detailed characterisation of system components as well as for comparisons across multiple instruments. PMID- 24224018 TI - Introducing the event related fixed interval area (ERFIA) multilevel technique: a method to analyze the complete epoch of event-related potentials at single trial level. AB - In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on this assumption, we introduce a new concept which allows for flexible investigation of the whole epoch and does not primarily focus on peaks and their corresponding latencies. For each trial, the entire epoch is partitioned into event-related fixed-interval areas under the curve (ERFIAs). These ERFIAs, obtained at single trial level, act as dependent variables in a multilevel random regression analysis. The ERFIA multilevel method was tested in an existing ERP dataset of 85 healthy subjects, who underwent a rating paradigm of 150 painful and non-painful somatosensory electrical stimuli. We modeled the variability of each consecutive ERFIA with a set of predictor variables among which were stimulus intensity and stimulus number. Furthermore, we corrected for latency variations of the P2 (260 ms). With respect to known relationships between stimulus intensity, habituation, and pain related somatosensory ERP, the ERFIA method generated highly comparable results to those of commonly used methods. Notably, effects on stimulus intensity and habituation were also observed in non-peak-related latency ranges. Further, cortical processing of actual stimulus intensity depended on the intensity of the previous stimulus, which may reflect pain-memory processing. In conclusion, the ERFIA multilevel method is a promising tool that can be used to study event related cortical processing. PMID- 24224019 TI - Genome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga Chlamydomonas reinhardtii under carbon deprivation. AB - The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO2], a carbon concentrating mechanism (CCM) is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing) to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1) gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF) and transcription regulator (TR) genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment) method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO 2 response regulator 1) and Lcr2 (Low-CO2 response regulator 2), may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome. Our work can serve as a basis for future functional studies of transcriptional regulator genes and genomic regulatory elements in Chlamydomonas. PMID- 24224020 TI - Identification of a functional nuclear localization signal mediating nuclear import of the zinc finger transcription factor ZNF24. AB - ZNF24 is a member of the SCAN domain family of Kruppel-like zinc finger (ZF) transcription factors, which plays a critical role in cell proliferation and differentiation. However, how ZNF24 enters the nucleus in order to exert its function remains unclear since its nuclear localization signal(s) (NLS) has not been identified. Here, we generated a series of GFP-tagged deletion and point mutants and assessed their subcellular localization. Our results delimit the NLS to ZF1-2. Deletion of ZF1-2 caused cytoplasmic accumulation of ZNF24. Fusion of the ZF1-2 to green fluorescent protein (GFP) targeted GFP to the nucleus, demonstrating that the ZF1-2 is both necessary and sufficient for nuclear localization. ZNF24 containing histidine to leucine mutations that disrupt the structure of ZF1 or/and ZF2 retains appropriate nuclear localization, indicating that neither the tertiary structure of the zinc fingers nor specific DNA binding are necessary for nuclear localization. K286A and R290A mutation led to partial cytoplasmic accumulation. Co-immunoprecipitation demonstrated that ZNF24 interacted with importin-beta and this interaction required the ZF motifs. The beta-Catenin (CTNNB1) luciferase assays showed that the ZNF24 mutants defective in nuclear localization could not promote CTNNB1 promoter activation as the wild type ZNF24 did. Taken together, these results suggest that consecutive ZF1-2 is critical for the regulation of ZNF24 nuclear localization and its transactivation function. PMID- 24224021 TI - Severe painful vaso-occlusive crises and mortality in a contemporary adult sickle cell anemia cohort study. AB - BACKGROUND: Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort. METHODS: Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation. RESULTS: Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality. CONCLUSIONS: Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/ PMID- 24224022 TI - Mechanical-stretch of C2C12 myoblasts inhibits expression of Toll-like receptor 3 (TLR3) and of autoantigens associated with inflammatory myopathies. AB - Recent studies in patients suffering from inflammatory autoimmune myopathies suggested that moderate exercise training improves or at least stabilizes muscle strength and function without inducing disease flares. However, the precise mechanisms involved in this beneficial effect have not been extensively studied. Here we used a model of in vitro stretched C2C12 myoblasts to investigate whether mechanical stretch could influence myoblast proliferation or the expression of proinflammatory genes. Our results demonstrated that cyclic mechanical stretch stimulated C2C12 cell cycling and early up-regulation of the molecules related to mechanical-stretch pathway in muscle (calmodulin, nNOS, MMP-2, HGF and c-Met). Unexpectedly, mechanical stretch also reduced the expression of TLR3 and of proteins known to represent autoantigens in inflammatory autoimmune myopathies (Mi-2, HRS, DNA-PKcs, U1-70). Interestingly, stimulation or inhibition of calmodulin, NOS, HGF or c-Met molecules in vitro affected the expression of autoantigens and TLR3 proteins confirming their role in the inhibition of autoantigens and TLR3 during mechanical stretch. Overall, this study demonstrates for the first time that mechanical stretch could be beneficial by reducing expression of muscle autoantigens and of pro-inflammatory TLR3 and may provide new insight to understand how resistance training can reduce the symptoms associated with myositis. PMID- 24224023 TI - Gene flow between sympatric life history forms of Oncorhynchus mykiss located above and below migratory barriers. AB - Oncorhynchus mykiss have a diverse array of life history types, and understanding the relationship among types is important for management of the species. Patterns of gene flow between sympatric freshwater resident O. mykiss, commonly known as rainbow trout, and anadromous O. mykiss, commonly known as steelhead, populations are complex and poorly understood. In this study, we attempt to determine the occurrence and pathways of gene flow and the degree of genetic similarity between sympatric resident and anadromous O. mykiss in three river systems, and investigate whether resident O. mykiss are producing anadromous offspring in these rivers, two of which have complete barriers to upstream migration. We found that the population structure of the O. mykiss in these rivers appears to be influenced more by the presence of a barrier to upstream migration than by life history type. The sex ratio of resident O. mykiss located above a barrier, and smolts captured in screw traps was significantly skewed in favor of females, whereas the reverse was true below the barriers, suggesting that male resident O. mykiss readily migrate downstream over the barrier, and that precocious male maturation may be occurring in the anadromous populations. Through paternity analyses, we also provide direct confirmation that resident O. mykiss can produce offspring that become anadromous. Most (89%) of the resident O. mykiss that produced anadromous offspring were males. Our results add to the growing body of evidence that shows that gene flow does readily occur between sympatric resident and anadromous O. mykiss life history types, and indicates that resident O. mykiss populations may be a potential repository of genes for the anadromous life history type. PMID- 24224024 TI - Prevalence of overweight and obesity and their associations with socioeconomic status in a rural Han Chinese adult population. AB - BACKGROUND: The purpose of this study is to describe the prevalence of overweight, general obesity, and abdominal obesity and examine their associations with socioeconomic status in a rural Chinese adult population. METHODS: This cross-sectional study was performed on 15,236 participants >= 35 years of age (6,313 men [41.4%] and 8,923 women [58.6%]). Each participant's weight, height, waist circumference (WC), and hipline circumference (HC) were measured, and demographic and socioeconomic data were collected using questionnaires. RESULTS: The mean body mass index (BMI) values were 23.31 +/- 2.96 and 23.89 +/- 3.23 kg m(-2) and the mean WC values were 79.13 +/- 8.43 and 79.54 +/- 8.27 cm for men and women, respectively. The age-standardized prevalence rates of overweight (BMI >= 24.0 kg m(-2)), general obesity (BMI >= 28.0 kg m(-2)), and abdominal obesity (WC >= 85 cm for men and >= 80 cm for women) were 32.0%, 6.7%, and 27.0% for men and 35.1%, 9.7%, and 48.3% for women, respectively. All gender differences were statistically significant (p < 0.001). In addition, the age-specific prevalence rates of general and abdominal obesity slowly decreased among men but sharply increased among women as age increased (p < 0.001). In subsequent logistic regression analysis, educational level was negatively associated with both general obesity and abdominal obesity among women but positively associated with abdominal obesity among men. No significant correlation was found between obesity and income. CONCLUSIONS: These results suggest a high prevalence of obesity which might differ by gender and age, and an inverse association among women and a mixed association among men noted between education and obesity in our locality. Preventive and therapeutic programs are warranted to control this serious public health problem. The gender-specific characteristics of populations at high-risk of developing obesity should be taken into consideration when designing interventional programs. PMID- 24224025 TI - Rural-urban differences in the long-term care of the disabled elderly in China. AB - BACKGROUND: In China, the rapid rate of population aging and changes in the prevalence of disability among elderly people could have significant effects on the demand for long-term care. This study aims to describe the urban-rural differences in use and cost of long-term care of the disabled elderly and to explore potential influencing factors. METHODS: This study uses data from a cross sectional survey and a qualitative investigation conducted in Zhejiang province in 2012. The participants were 826 individuals over 60 years of age, who had been bedridden or suffered from dementia for more than 6 months. A generalized linear model and two-part regression model were applied to estimate costs, with adjustment of covariates. RESULTS: Pensions provide the main source of income for urban elderly, while the principal income source for rural elderly is their family. Urban residents spend more on all services than do rural residents. Those who are married spend less on daily supplies and formal care than the unmarried do. Age, incapacitation time, comorbidity number, level of income, and bedridden status influence spending on medical care (beta=-0.0316, -0.0206, 0.1882, 0.3444, and -0.4281, respectively), but the cost does not increase as the elderly grow older. Urban residents, the married, and those with a higher income level tend to spend more on medical equipment. Urban residence and living status are the two significant factors that affect spending on personal hygiene products. CONCLUSIONS: The use of long-term care services varies by living area. Long-term care of the disabled elderly imposes a substantial burden on families. Our study revealed that informal care involves huge opportunity costs to the caregivers. Chinese policy makers need to promote community care and long-term care insurance to relieve the burden of families of disabled elderly, and particular attention should be given to the rural elderly. PMID- 24224026 TI - Persistence of coastal vegetation in supratidal zones of northern China. AB - Coastal vegetation comprises a number of coastal specialists and terrestrial generalists. It remains unclear how they persist on disturbed and undisturbed coastal conditions. We tested the hypothesis that coastal specialists may be superior to terrestrial generalists on supratidal zones of coasts, but their superiority can be influenced by human disturbances. Eight separate sandy coasts of the Shandong Peninsula were sampled, representing for disturbed and undisturbed sandy coasts. Plants growing on their supratidal zones were surveyed. On this basis, we compared the relative dominances, niche widths, and commonness of all species, and also analyzed species diversities of the coasts. Coastal specialists were found to be more common and widespread on supratidal zones of the sandy coasts than terrestrial generalists haphazardly invading from hinterlands. Coastal specialists exhibited lower Sorensen dissimilarities than terrestrial generalists among the coasts. Tourist trampling seemed more detrimental than pond fishery to coastal vegetation. Relative to terrestrial generalists, coastal specialists responded to human disturbances more deterministically, with steady decreases in species diversities. These evidences verify that coastal specialists are intrinsically superior to terrestrial generalists on supratidal zones of coasts, especially of undisturbed coasts, because their dispersal among coasts adapts well to local storm surge regime. They also validate that human disturbances can depress the superiority of coastal specialists, partly by inducing invasion of terrestrial generalists. PMID- 24224028 TI - The long term economic impact of severe obstetric complications for women and their children in Burkina Faso. AB - This study investigates the long term economic impact of severe obstetric complications for women and their children in Burkina Faso, focusing on measures of food security, expenditures and related quality of life measures. It uses a hospital based cohort, first visited in 2004/2005 and followed up four years later. This cohort of 1014 women consisted of two main groups of comparison: 677 women who had an uncomplicated delivery and 337 women who experienced a severe obstetric complication which would have almost certainly caused death had they not received hospital care (labelled a "near miss" event). To analyze the impact of such near miss events as well as the possible interaction with the pregnancy outcome, we compared household and individual level indicators between women without a near miss event and women with a near miss event who either had a live birth, a perinatal death or an early pregnancy loss. We used propensity score matching to remove initial selection bias. Although we found limited effects for the whole group of near miss women, the results indicated negative impacts: a) for near miss women with a live birth, on child development and education, on relatively expensive food consumption and on women's quality of life; b) for near miss women with perinatal death, on relatively expensive foods consumption and children's education and c) for near miss women who had an early pregnancy loss, on overall food security. Our results showed that severe obstetric complications have long lasting consequences for different groups of women and their children and highlighted the need for carefully targeted interventions. PMID- 24224027 TI - Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism. AB - Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP directed conditional gene knockout system, we generated an inducible Arg1 deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2) mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency. PMID- 24224029 TI - Treatment and prognosis of anaplastic thyroid carcinoma: experience from a single institution in China. AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed. METHODS: Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan-Meier). Multivariate analysis was performed using a Cox proportional hazards model. RESULTS: Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 * 10(9)/L or blood platelet (PLT) counts < 300.0 * 10(9)/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses >= 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival. CONCLUSIONS: We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count >= 10.0*10(9)/L, a PLT count >= 300.0 * 10(9)/L, or age >= 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease. PMID- 24224030 TI - Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice. AB - Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE) or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments. PMID- 24224031 TI - Bias in diet determination: incorporating traditional methods in Bayesian mixing models. AB - There are not "universal methods" to determine diet composition of predators. Most traditional methods are biased because of their reliance on differential digestibility and the recovery of hard items. By relying on assimilated food, stable isotope and Bayesian mixing models (SIMMs) resolve many biases of traditional methods. SIMMs can incorporate prior information (i.e. proportional diet composition) that may improve the precision in the estimated dietary composition. However few studies have assessed the performance of traditional methods and SIMMs with and without informative priors to study the predators' diets. Here we compare the diet compositions of the South American fur seal and sea lions obtained by scats analysis and by SIMMs-UP (uninformative priors) and assess whether informative priors (SIMMs-IP) from the scat analysis improved the estimated diet composition compared to SIMMs-UP. According to the SIMM-UP, while pelagic species dominated the fur seal's diet the sea lion's did not have a clear dominance of any prey. In contrast, SIMM-IP's diets compositions were dominated by the same preys as in scat analyses. When prior information influenced SIMMs' estimates, incorporating informative priors improved the precision in the estimated diet composition at the risk of inducing biases in the estimates. If preys isotopic data allow discriminating preys' contributions to diets, informative priors should lead to more precise but unbiased estimated diet composition. Just as estimates of diet composition obtained from traditional methods are critically interpreted because of their biases, care must be exercised when interpreting diet composition obtained by SIMMs-IP. The best approach to obtain a near-complete view of predators' diet composition should involve the simultaneous consideration of different sources of partial evidence (traditional methods, SIMM-UP and SIMM-IP) in the light of natural history of the predator species so as to reliably ascertain and weight the information yielded by each method. PMID- 24224032 TI - A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice. AB - OBJECTIVE: The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice. METHODS AND RESULTS: Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5%, p<0.01, and 47.8%, p<0.05, respectively). Four-week old male apoE-deficient mice were treated with SSR128129E (50 mg/kg/d) for 3 and 5 months in comparison with a control group. SSR128129E treatment resulted in a reduction of lesion size in the aortic sinus (16.4% (ns) at 3 months and 42.9% (p<0.01) at 5 months, without any change in serum lipids. SSR128129 significantly reduced FGFR2 mRNA levels in the aortic sinus (p<0.05, n=5-6), but did not affect the mRNA expression levels of other FGF receptors or ligands. CONCLUSION: These studies indicate that FGFs have an important role in the development of vascular diseases like atherosclerosis and graft arteriosclerosis. These data suggest that inhibition of FGF receptors by compounds like SSR128129E might be useful as a new therapeutic approach for these vascular pathologies. PMID- 24224033 TI - Effects of extreme weather on reproductive success in a temperate-breeding songbird. AB - The frequency of extreme meteorological events such as heat waves and rainstorms is predicted to increase with climate change. However, there is still little information about how extreme weather influences reproduction in animals. It may not only affect breeding success but might also alter offspring sex ratio if males and females are differentially sensitive to meteorological conditions during development. We investigated the relationship between meteorological conditions and reproductive success over 6 years in a house sparrow population in central Europe. We found that hatching success increased with the number of extremely hot days (daily maximum >31 degrees C) and decreased with the number of extremely cold days (<16 degrees C) during incubation, although the latter effect held only for clutches with relatively short incubation periods. Fledging success was unrelated to weather variables. However, the frequency of extremely hot days had a negative effect on fledglings' body mass and tarsus length, although both of these traits were positively related to average temperature. Additionally, fledglings' body mass increased with the length of period without rainfall before fledging. Male to female ratio among fledglings did not differ from 1:1 and did not vary with weather variables. The magnitude of the effects of extreme meteorological events was usually small, although in some cases comparable to those of ecologically relevant predictors of reproductive success. Our results indicate that meteorological conditions have complex effects on breeding success, as the effects of extreme weather can differ between different aspects of reproduction and also from the effects of overall meteorological conditions. PMID- 24224034 TI - Increased biomass, seed yield and stress tolerance is conferred in Arabidopsis by a novel enzyme from the resurrection grass Sporobolus stapfianus that glycosylates the strigolactone analogue GR24. AB - Isolation of gene transcripts from desiccated leaf tissues of the resurrection grass, Sporobolus stapfianus, resulted in the identification of a gene, SDG8i, encoding a Group 1 glycosyltransferase (UGT). Here, we examine the effects of introducing this gene, under control of the CaMV35S promoter, into the model plant Arabidopsis thaliana. Results show that Arabidopsis plants constitutively over-expressing SDG8i exhibit enhanced growth, reduced senescence, cold tolerance and a substantial improvement in protoplasmic drought tolerance. We hypothesise that expression of SDG8i in Arabidopsis negatively affects the bioactivity of metabolite/s that mediate/s environmentally-induced repression of cell division and expansion, both during normal development and in response to stress. The phenotype of transgenic plants over-expressing SDG8i suggests modulation in activities of both growth- and stress-related hormones. Plants overexpressing the UGT show evidence of elevated auxin levels, with the enzyme acting downstream of ABA to reduce drought-induced senescence. Analysis of the in vitro activity of the UGT recombinant protein product demonstrates that SDG8i can glycosylate the synthetic strigolactone analogue GR24, evoking a link with strigolactone-related processes in vivo. The large improvements observed in survival of transgenic Arabidopsis plants under cold-, salt- and drought-stress, as well as the substantial increases in growth rate and seed yield under non-stress conditions, indicates that overexpression of SDG8i in crop plants may provide a novel means of increasing plant productivity. PMID- 24224035 TI - Effect of GA3 treatment on seed development and seed-related gene expression in grape. AB - BACKGROUND: The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars ('Kyoho' and 'Red Globe'), along with a seedless cultivar ('Thompson Seedless'), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both 'Kyoho' and 'Red Globe' seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. CONCLUSION: Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development. PMID- 24224036 TI - Can winter-active bumblebees survive the cold? Assessing the cold tolerance of Bombus terrestris audax and the effects of pollen feeding. AB - There is now considerable evidence that climate change is disrupting the phenology of key pollinator species. The recently reported UK winter activity of the bumblebee Bombus terrestris brings a novel set of thermal challenges to bumblebee workers that would typically only be exposed to summer conditions. Here we assess the ability of workers to survive acute and chronic cold stress (via lower lethal temperatures and lower lethal times at 0 degrees C), the capacity for rapid cold hardening (RCH) and the influence of diet (pollen versus nectar consumption) on supercooling points (SCP). Comparisons are made with chronic cold stress indices and SCPs in queen bumblebees. Results showed worker bees were able to survive acute temperatures likely to be experienced in a mild winter, with queens significantly more tolerant to chronic cold temperature stress. The first evidence of RCH in any Hymenoptera is shown. In addition, dietary manipulation indicated the consumption of pollen significantly increased SCP temperature. These results are discussed in the light of winter active bumblebees and climate change. PMID- 24224038 TI - Direct RNA-based detection and differentiation of CTX-M-type extended-spectrum beta-lactamases (ESBL). AB - The current global spread of multi-resistant Gram-negatives, particularly extended spectrum beta-lactamases expressing bacteria, increases the likelihood of inappropriate empiric treatment of critically ill patients with subsequently increased mortality. From a clinical perspective, fast detection of resistant pathogens would allow a pre-emptive correction of an initially inappropriate treatment. Here we present diagnostic amplification-sequencing approach as proof of principal based on the fast molecular detection and correct discrimination of CTX-M-beta-lactamases, the most frequent ESBL family. The workflow consists of the isolation of total mRNA and CTX-M-specific reverse transcription (RT), amplification and pyrosequencing. Due to the high variability of the CTX-M-beta lactamase-genes, degenerated primers for RT, qRT as well as for pyrosequencing, were used and the suitability and discriminatory performance of two conserved positions within the CTX-M genes were analyzed, using one protocol for all isolates and positions, respectively. Using this approach, no information regarding the expected CTX-M variant is needed since all sequences are covered by these degenerated primers. The presented workflow can be conducted within eight hours and has the potential to be expanded to other beta-lactamase families. PMID- 24224037 TI - Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study. AB - PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1)H-MRS) in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B) to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A). After sixteen months post-procedure, (1)H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1)H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model. PMID- 24224039 TI - Changes in brain tissue and behavior patterns induced by single short-term fasting in mice. AB - In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis. PMID- 24224040 TI - L265P mutation of the MYD88 gene is frequent in Waldenstrom's macroglobulinemia and its absence in myeloma. AB - L265P mutation in the MYD88 gene has recently been reported in Waldenstrom's macroglobulinemia; however the incidence has been different according to the methods used. To determine the relevance and compare the incidence by different methods, we analyzed the L265P mutation in bone marrow mononuclear cells from lymphoid neoplasms. We first performed cloning and sequencing in 10 patients: 8 Waldenstrom's macroglobulinemia; 1 non-IgM-secreting lymphoplasmacytic lymphoma; and 1 low grade B-cell lymphoma with monoclonal IgG protein. The L265P mutation was detected in only 1/8 Waldenstrom's macroglobulinemia patients (2 of 9 clones). To confirm these results, direct sequencing was performed in the 10 patients and an additional 17 Waldenstrom's macroglobulinemia patients and 1 lymphoplasmacytic lymphoma patient. Nine of 28 patients (7/25 Waldenstrom's macroglobulinemia, 1/2 lymphoplasmacytic lymphoma, and B-cell lymphoma) harbored the mutation. We next tested for the mutation with BSiE1 digestion and allele specific polymerase chain reaction in the 28 patients and 38 patients with myeloma. Aberrant bands corresponding to the mutation were detected by BSiE1 digestion in 19/25 patients with Waldenstrom's macroglobulinemia (76%), 1/2 lymphoplasmacytic lymphoma and B-cell lymphoma, but not in the 38 myeloma patients. The L265P mutation was more frequent in patients with Waldenstrom's macroglobulinemia than in those with myeloma (p=1.3x10(-10)). The mutation was detected by allele-specific polymerase chain reaction in 18/25 Waldenstrom's macroglobulinemia patients (72%). In the 25 Waldenstrom's macroglobulinemia patients, the L265P was more frequently detected by BSiE1 digestion than by direct sequencing (p=5.3x10(-4)), and in males (15/16, 94%) than in females (4/9, 44%) (p=1.2x10(-2)). No siginificant difference was observed in the incidence of the L265P mutation between BSiE1 digestion and allele-specific polymerase chain reaction (p=0.32). These results suggest that the L265P mutation is involved in the majority of Waldenstrom's macroglobulinemia. BSiE1 digestion and allele specific polymerase chain reaction may detect a small fraction of mutated cells in some cases. PMID- 24224041 TI - Simplified large-scale refolding, purification, and characterization of recombinant human granulocyte-colony stimulating factor in Escherichia coli. AB - Granulocyte-colony stimulating factor (G-CSF) is a pleiotropic cytokine that stimulates the development of committed hematopoietic progenitor cells and enhances the functional activity of mature cells. Here, we report a simplified method for fed-batch culture as well as the purification of recombinant human (rh) G-CSF. The new system for rhG-CSF purification was performed using not only temperature shift strategy without isopropyl-l-thio-beta-d-galactoside (IPTG) induction but also the purification method by a single step of prep-HPLC after the pH precipitation of the refolded samples. Through these processes, the final cell density and overall yield of homogenous rhG-CSF were obtained 42.8 g as dry cell weights, 1.75 g as purified active proteins, from 1 L culture broth, respectively. The purity of rhG-CSF was finally 99% since the isoforms of rhG-CSF could be separated through the prep-HPLC step. The result of biological activity indicated that purified rhG-CSF has a similar profile to the World Health Organization (WHO) 2(nd) International Standard for G-CSF. Taken together, our results demonstrate that the simple purification through a single step of prep HPLC may be valuable for the industrial-scale production of biologically active proteins. PMID- 24224042 TI - Effects of antioxidant treatment on blast-induced brain injury. AB - Blast-induced traumatic brain injury has dramatically increased in combat troops in today's military operations. We previously reported that antioxidant treatment can provide protection to the peripheral auditory end organ, the cochlea. In the present study, we examined biomarker expression in the brains of rats at different time points (3 hours to 21 days) after three successive 14 psi blast overpressure exposures to evaluate antioxidant treatment effects on blast-induced brain injury. Rats in the treatment groups received a combination of antioxidants (2,4-disulfonyl alpha-phenyl tertiary butyl nitrone and N-acetylcysteine) one hour after blast exposure and then twice a day for the following two days. The biomarkers examined included an oxidative stress marker (4-hydroxy-2-nonenal, 4 HNE), an immediate early gene (c-fos), a neural injury marker (glial fibrillary acidic protein, GFAP) and two axonal injury markers [amyloid beta (A4) precursor protein, APP, and 68 kDa neurofilament, NF-68]. The results demonstrate that blast exposure induced or up-regulated the following: 4-HNE production in the dorsal hippocampus commissure and the forceps major corpus callosum near the lateral ventricle; c-fos and GFAP expression in most regions of the brain, including the retrosplenial cortex, the hippocampus, the cochlear nucleus, and the inferior colliculus; and NF-68 and APP expression in the hippocampus, the auditory cortex, and the medial geniculate nucleus (MGN). Antioxidant treatment reduced the following: 4-HNE in the hippocampus and the forceps major corpus callosum, c-fos expression in the retrosplenial cortex, GFAP expression in the dorsal cochlear nucleus (DCN), and APP and NF-68 expression in the hippocampus, auditory cortex, and MGN. This preliminary study indicates that antioxidant treatment may provide therapeutic protection to the central auditory pathway (the DCN and MGN) and the non-auditory central nervous system (hippocampus and retrosplenial cortex), suggesting that these compounds have the potential to simultaneously treat blast-induced injuries in the brain and auditory system. PMID- 24224043 TI - In vitro detection of prionemia in TSE-infected cervids and hamsters. AB - Blood-borne transmission of infectious prions during the symptomatic and asymptomatic stages of disease occurs for both human and animal transmissible spongiform encephalopathies (TSEs). The geographical distribution of the cervid TSE, chronic wasting disease (CWD), continues to spread across North America and the prospective number of individuals harboring an asymptomatic infection of human variant Creutzfeldt-Jakob Disease (vCJD) in the United Kingdom has been projected to be ~1 in 3000 residents. Thus, it is important to monitor cervid and human blood products to ensure herd health and human safety. Current methods for detecting blood-associated prions rely primarily upon bioassay in laboratory animals. While bioassay provides high sensitivity and specificity, it requires many months, animals, and it is costly. Here we report modification of the real time quaking-induced conversion (RT-QuIC) assay to detect blood-borne prions in whole blood from prion-infected preclinical white-tailed deer, muntjac deer, and Syrian hamsters, attaining sensitivity of >90% while maintaining 100% specificity. Our results indicate that RT-QuIC methodology as modified can provide consistent and reliable detection of blood-borne prions in preclinical and symptomatic stages of two animal TSEs, offering promise for prionemia detection in other species, including humans. PMID- 24224044 TI - Grey matter correlates of three language tests in non-demented older adults. AB - Language has been extensively investigated by functional neuroimaging studies. However, only a limited number of structural neuroimaging studies have examined the relationship between language performance and brain structure in healthy adults, and the number is even less in older adults. The present study sought to investigate correlations between grey matter volumes and three standardized language tests in late life. The participants were 344 non-demented, community dwelling adults aged 70-90 years, who were drawn from the population-based Sydney Memory and Ageing Study. The three language tests included the Controlled Oral Word Association Task (COWAT), Category Fluency (CF), and Boston Naming Test (BNT). Correlation analyses between voxel-wise GM volumes and language tests showed distinctive GM correlation patterns for each language test. The GM correlates were located in the right frontal and left temporal lobes for COWAT, in the left frontal and temporal lobes for CF, and in bilateral temporal lobes for BNT. Our findings largely corresponded to the neural substrates of language tasks revealed in fMRI studies, and we also observed a less hemispheric asymmetry in the GM correlates of the language tests. Furthermore, we divided the participants into two age groups (70-79 and 80-90 years old), and then examined the correlations between structural laterality indices and language performance for each group. A trend toward significant difference in the correlations was found between the two age groups, with stronger correlations in the group of 70 79 years old than those in the group of 80-90 years old. This difference might suggest a further decline of language lateralization in different stages of late life. PMID- 24224045 TI - Transcriptome analysis reveals crosstalk of responsive genes to multiple abiotic stresses in cotton (Gossypium hirsutum L.). AB - Abiotic stress is a major environmental factor that limits cotton growth and yield, moreover, this problem has become more and more serious recently, as multiple stresses often occur simultaneously due to the global climate change and environmental pollution. In this study, we sought to identify genes involved in diverse stresses including abscisic acid (ABA), cold, drought, salinity and alkalinity by comparative microarray analysis. Our result showed that 5790, 3067, 5608, 778 and 6148 transcripts, were differentially expressed in cotton seedlings under treatment of ABA (1 MUM ABA), cold (4 degrees C), drought (200 mM mannitol), salinity (200 mM NaCl) and alkalinity (pH=11) respectively. Among the induced or suppressed genes, 126 transcripts were shared by all of the five kinds of abiotic stresses, with 64 up-regulated and 62 down-regulated. These common members are grouped as stress signal transduction, transcription factors (TFs), stress response/defense proteins, metabolism, transport facilitation, as well as cell wall/structure, according to the function annotation. We also noticed that large proportion of significant differentially expressed genes specifically regulated in response to different stress. Nine of the common transcripts of multiple stresses were selected for further validation with quantitative real time RT-PCR (qRT-PCR). Furthermore, several well characterized TF families, for example, WRKY, MYB, NAC, AP2/ERF and zinc finger were shown to be involved in different stresses. As an original report using comparative microarray to analyze transcriptome of cotton under five abiotic stresses, valuable information about functional genes and related pathways of anti-stress, and/or stress tolerance in cotton seedlings was unveiled in our result. Besides this, some important common factors were focused for detailed identification and characterization. According to our analysis, it suggested that there was crosstalk of responsive genes or pathways to multiple abiotic or even biotic stresses, in cotton. These candidate genes will be worthy of functional study under diverse stresses. PMID- 24224046 TI - Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin. AB - OBJECTIVES: The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The OncoCarta(TM) panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico pathological characteristics and risk habits. RESULTS: Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits. CONCLUSION: Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools. PMID- 24224047 TI - Heme oxygenase-1 (HO-1) expression in prostate cancer cells modulates the oxidative response in bone cells. AB - Prostate cancer (PCa) is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1) counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs), we demonstrated that HO-1 pharmacological induction (hemin treatment) abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre treated PC3 cells (PC3 Hem) with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1) cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis. PMID- 24224048 TI - Abnormal trafficking of endogenously expressed BMPR2 mutant allelic products in patients with heritable pulmonary arterial hypertension. AB - More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predicted to express BMPR2 mutant products. However expression of endogenous NMD negative BMPR2 mutant products and their effect on protein trafficking and signaling function have never been described. Here, we characterize the expression and trafficking of an HPAH-associated NMD negative BMPR2 mutation that results in an in-frame deletion of BMPR2 EXON2 (BMPR2DeltaEx2) in HPAH patient-derived lymphocytes and in pulmonary endothelial cells (PECs) from mice carrying the same in-frame deletion of Exon 2 (Bmpr2 (DeltaEx2/+) mice). The endogenous BMPR2DeltaEx2 mutant product does not reach the cell surface and is retained in the endoplasmic reticulum. Moreover, chemical chaperones 4-PBA and TUDCA partially restore cell surface expression of Bmpr2DeltaEx2 in PECs, suggesting that the mutant product is mis-folded. We also show that PECs from Bmpr2 (DeltaEx2/+) mice have defects in the BMP-induced Smad1/5/8 and Id1 signaling axis, and that addition of chemical chaperones restores expression of the Smad1/5/8 target Id1. These data indicate that the endogenous NMD negative BMPRDeltaEx2 mutant product is expressed but has a folding defect resulting in ER retention. Partial correction of this folding defect and restoration of defective BMP signaling using chemical chaperones suggests that protein-folding agents could be used therapeutically in patients with these NMD negative BMPR2 mutations. PMID- 24224049 TI - Prevalence and risk factors for refractive errors: Korean National Health and Nutrition Examination Survey 2008-2011. AB - PURPOSE: To examine the prevalence and risk factors of refractive errors in a representative Korean population aged 20 years old or older. METHODS: A total of 23,392 people aged 20+ years were selected for the Korean National Health and Nutrition Survey 2008-2011, using stratified, multistage, clustered sampling. Refractive error was measured by autorefraction without cycloplegia, and interviews were performed regarding associated risk factors including gender, age, height, education level, parent's education level, economic status, light exposure time, and current smoking history. RESULTS: Of 23,392 participants, refractive errors were examined in 22,562 persons, including 21,356 subjects with phakic eyes. The overall prevalences of myopia (< -0.5 D), high myopia (< -6.0 D), and hyperopia (> 0.5 D) were 48.1% (95% confidence interval [CI], 47.4-48.8), 4.0% (CI, 3.7-4.3), and 24.2% (CI, 23.6-24.8), respectively. The prevalence of myopia sharply decreased from 78.9% (CI, 77.4-80.4) in 20-29 year olds to 16.1% (CI, 14.9-17.3) in 60-69 year olds. In multivariable logistic regression analyses restricted to subjects aged 40+ years, myopia was associated with younger age (odds ratio [OR], 0.94; 95% Confidence Interval [CI], 0.93-0.94, p < 0.001), education level of university or higher (OR, 2.31; CI, 1.97-2.71, p < 0.001), and shorter sunlight exposure time (OR, 0.84; CI, 0.76-0.93, p = 0.002). CONCLUSIONS: This study provides the first representative population-based data on refractive error for Korean adults. The prevalence of myopia in Korean adults in 40+ years (34.7%) was comparable to that in other Asian countries. These results show that the younger generations in Korea are much more myopic than previous generations, and that important factors associated with this increase are increased education levels and reduced sunlight exposures. PMID- 24224050 TI - Activity patterns of free-ranging koalas (Phascolarctos cinereus) revealed by accelerometry. AB - An understanding of koala activity patterns is important for measuring the behavioral response of this species to environmental change, but to date has been limited by the logistical challenges of traditional field methodologies. We addressed this knowledge gap by using tri-axial accelerometer data loggers attached to VHF radio collars to examine activity patterns of adult male and female koalas in a high-density population at Cape Otway, Victoria, Australia. Data were obtained from 27 adult koalas over two 7-d periods during the breeding season: 12 in the early-breeding season in November 2010, and 15 in the late breeding season in January 2011. Multiple 15 minute observation blocks on each animal were used for validation of activity patterns determined from the accelerometer data loggers. Accelerometry was effective in distinguishing between inactive (sleeping, resting) and active (grooming, feeding and moving) behaviors. Koalas were more active during the early-breeding season with a higher index of movement (overall dynamic body acceleration [ODBA]) for both males and females. Koalas showed a distinct temporal pattern of behavior, with most activity occurring from mid-afternoon to early morning. Accelerometry has potential for examining fine-scale behavior of a wide range of arboreal and terrestrial species. PMID- 24224051 TI - Solution and crystallographic structures of the central region of the phosphoprotein from human metapneumovirus. AB - Human metapneumovirus (HMPV) of the family Paramyxoviridae is a major cause of respiratory illness worldwide. Phosphoproteins (P) from Paramyxoviridae are essential co-factors of the viral RNA polymerase that form tetramers and possess long intrinsically disordered regions (IDRs). We located the central region of HMPV P (P(ced)) which is involved in tetramerization using disorder analysis and modeled its 3D structure ab initio using Rosetta fold-and-dock. We characterized the solution-structure of P(ced) using small angle X-ray scattering (SAXS) and carried out direct fitting to the scattering data to filter out incorrect models. Molecular dynamics simulations (MDS) and ensemble optimization were employed to select correct models and capture the dynamic character of P(ced). Our analysis revealed that oligomerization involves a compact central core located between residues 169-194 (P(core)), that is surrounded by flexible regions with alpha helical propensity. We crystallized this fragment and solved its structure at 3.1 A resolution by molecular replacement, using the folded core from our SAXS validated ab initio model. The RMSD between modeled and experimental tetramers is as low as 0.9 A, demonstrating the accuracy of the approach. A comparison of the structure of HMPV P to existing mononegavirales P(ced) structures suggests that P(ced) evolved under weak selective pressure. Finally, we discuss the advantages of using SAXS in combination with ab initio modeling and MDS to solve the structure of small, homo-oligomeric protein complexes. PMID- 24224052 TI - Foot drop caused by lumbar degenerative disease: clinical features, prognostic factors of surgical outcome and clinical stage. AB - OBJECTIVE: The purpose of this study was to analyze the clinical features and prognostic factors of surgical outcome of foot drop caused by lumbar degenerative disease and put forward the clinical stage. METHODS: We retrospectively reviewed 135 patients with foot drop due to lumbar degenerative disease. The clinical features and mechanism were analyzed. Age, sex, duration of palsy, preoperative muscle strength of tibialis anterior (TA), sensation defect of affected lower limb, affected foot, diagnosis and compressed nerve roots were recorded and compared with surgical outcome. RESULTS: Foot drop was observed in 8.1% of all inpatients of lumbar degenerative disease. L5 nerve root compression was observed in 126 of all 135 patients (93.3%). Single, double and triple roots compression was observed respectively in 43, 83, and 9 patients (31.9%, 61.5%, and 6.6%). But there was no significant relationship between preoperative muscle strength of TA and the number of compressed roots. The muscle strength of TA was improved in 113 (83.7%) patients after surgery, but it reached to >=4 in only 21 (15.6%) patients. Improvement of the muscle strength of TA was almost stable at the 6 month follow-up. At the last follow-up, the muscle strength of TA was 1, 2, 3, 4, 5 respectively in 28, 24, 62, 13, 8 patients. Multivariate logistic regression showed duration of palsy (p=0.0360, OR=2.543), preoperative muscle strength of TA (p=0.0064, OR=5.528) and age (p=0.0309, OR=3.208) were factors that influenced recovery following an operation. CONCLUSIONS: L5 nerve root was most frequently affected. The muscle strength of TA improved in most patients after surgery, but few patients can get a good recovery from foot drop. Patients of shorter duration of palsy, better preoperative muscle strength of TA and younger age showed a better surgical outcome. PMID- 24224053 TI - The neural basis of responsibility attribution in decision-making. AB - Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID- 24224054 TI - Multisensory control of multimodal behavior: do the legs know what the tongue is doing? AB - Understanding of adaptive behavior requires the precisely controlled presentation of multisensory stimuli combined with simultaneous measurement of multiple behavioral modalities. Hence, we developed a virtual reality apparatus that allows for simultaneous measurement of reward checking, a commonly used measure in associative learning paradigms, and navigational behavior, along with precisely controlled presentation of visual, auditory and reward stimuli. Rats performed a virtual spatial navigation task analogous to the Morris maze where only distal visual or auditory cues provided spatial information. Spatial navigation and reward checking maps showed experience-dependent learning and were in register for distal visual cues. However, they showed a dissociation, whereby distal auditory cues failed to support spatial navigation but did support spatially localized reward checking. These findings indicate that rats can navigate in virtual space with only distal visual cues, without significant vestibular or other sensory inputs. Furthermore, they reveal the simultaneous dissociation between two reward-driven behaviors. PMID- 24224055 TI - APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival. AB - beta-Amyloid precursor protein (APP) is a key factor in Alzheimer's disease (AD) but its physiological function is largely undetermined. APP has been found to regulate retrograde transport of nerve growth factor (NGF), which plays a crucial role in mediating neuronal survival and differentiation. Herein, we reveal the mechanism underlying APP-mediated NGF trafficking, by demonstrating a direct interaction between APP and the two NGF receptors, TrkA and p75NTR. Downregulation of APP leads to reduced cell surface levels of TrkA/p75NTR and increased endocytosis of TrkA/p75NTR and NGF. In addition, APP-deficient cells manifest defects in neurite outgrowth and are more susceptible to Abeta-induced neuronal death at physiological levels of NGF. However, APP-deficient cells show better responses to NGF-stimulated differentiation and survival than control cells. This may be attributed to increased receptor endocytosis and enhanced activation of Akt and MAPK upon NGF stimulation in APP-deficient cells. Together, our results suggest that APP mediates endocytosis of NGF receptors through direct interaction, thereby regulating endocytosis of NGF and NGF-induced downstream signaling pathways for neuronal survival and differentiation. PMID- 24224056 TI - The transcription factors Atf1 and Pcr1 are essential for transcriptional induction of the extracellular maltase Agl1 in fission yeast. AB - The fission yeast Schizosaccharomyces pombe secretes the extracellular maltase Agl1, which hydrolyzes maltose into glucose, thereby utilizing maltose as a carbon source. Whether other maltases contribute to efficient utilization of maltose and how Agl1 expression is regulated in response to switching of carbon sources are unknown. In this study, we show that three other possible maltases and the maltose transporter Sut1 are not required for efficient utilization of maltose. Transcription of agl1 was induced when the carbon source was changed from glucose to maltose. This was dependent on Atf1 and Pcr1, which are highly conserved transcription factors that regulate stress-responsive genes in various stress conditions. Atf1 and Pcr1 generally bind the TGACGT motif as a heterodimer. The agl1 gene lacks the exact motif, but has many degenerate TGACGT motifs in its promoter and coding region. When the carbon source was switched from glucose to maltose, Atf1 and Pcr1 associated with the promoters and coding regions of agl1, fbp1, and gpx1, indicating that the Atf1-Pcr1 heteromer binds a variety of regions in its target genes to induce their transcription. In addition, the association of Mediator with these genes was dependent on Atf1 and Pcr1. These data indicate that Atf1 and Pcr1 induce the transcription of agl1, which allows efficient utilization of extracellular maltose. PMID- 24224057 TI - Outcomes of extensive hybridization and introgression in Epidendrum (Orchidaceae): can we rely on species boundaries? AB - Hybridization has the potential to contribute to phenotypic and genetic variation and can be a major evolutionary mechanism. However, when hybridization is extensive it can also lead to the blurring of species boundaries and the emergence of cryptic species (i.e., two or more species not distinguishable morphologically). In this study, we address this hypothesis in Epidendrum, the largest Neotropical genus of orchids where hybridization is apparently so common that it may explain the high levels of morphological diversity found. Nonetheless, this hypothesis is mostly based on the intermediacy of morphological characters and intermediacy by itself is not a proof of hybridization. Therefore, in this study, we first assessed the existence of hybrids using cpDNA and AFLP data gathered from a large-scale sampling comprising 1038 plants of three species of Epidendrum (E. calanthum, E. cochlidium and E. schistochilum). Subsequently, a Bayesian assignment of individuals into different genetic classes (pure species, F1, F2 or backcross generations) revealed that hybrid genotypes were prevalent in all sympatric populations. In most cases, parental species were not assigned as pure individuals, rather consisting in backcrossed genotypes or F1 hybrids. We also found that reproductive barriers are apparently very weak in Epidendrum because the three species largely overlapped in their flowering periods and interspecific crosses always produced viable seeds. Further, hybridization contributed to enhance floral variability, genome size and reproductive success since we found that these traits were always higher in hybrid classes (F1, F2 and backcrosses) than in pure parental species, and offer an explanation for the blurring of species boundaries in this genus of orchids. We hypothesize that these natural hybrids possess an evolutionary advantage, which may explain the high rates of cryptic species observed in this genus. PMID- 24224058 TI - Gr1(int)CD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection. AB - BACKGROUND: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(int)CD11b(+) cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. METHODOLOGY/PRINCIPAL FINDINGS: We compared the bacterial burden, lung pathology and Gr1(int)CD11b(+) myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+) cells could be found on the edges of necrotic lung lesions in NOS2 /-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi) and Gr1(int) populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int) populations at different ratios with naive or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased. Our results illustrate a yet unrecognized interplay between Gr1(+) cells and CD4(+) T cells in tuberculosis. PMID- 24224059 TI - Developmental switch in neurovascular coupling in the immature rodent barrel cortex. AB - Neurovascular coupling (NVC) in the adult central nervous system (CNS) is a mechanism that provides regions of the brain with more oxygen and glucose upon increased levels of neural activation. Hemodynamic changes that go along with neural activation evoke a blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) that can be used to study brain activity non-invasively. A correct correlation of the BOLD signal to neural activity is pivotal to understand this signal in neuronal development, health and disease. However, the function of NVC during development is largely unknown. The rodent whisker-to-barrel cortex is an experimentally well established model to study neurovascular interdependences. Using extracellular multi-electrode recordings and laser-Doppler-flowmetry (LDF) we show in the murine barrel cortex of postnatal day 7 (P7) and P30 mice in vivo that NVC undergoes a physiological shift during the first month of life. In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF). We show in P7 animals that rCBF decreases during prolonged multi-whisker stimulation and goes along with multi unit activity (MUA) fatigue. In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF. Further we characterize in both age groups the responses in NVC to single sensory stimuli. We suggest that the observed shift in NVC is an important process in cortical development that may be of high relevance for the correct interpretation of brain activity e.g. in fMRI studies of the immature central nervous system (CNS). PMID- 24224061 TI - Isoaspartate accumulation in mouse brain is associated with altered patterns of protein phosphorylation and acetylation, some of which are highly sex-dependent. AB - Isoaspartate (isoAsp) formation is a major source of protein damage that is kept in check by the repair function of protein L-isoaspartyl methyltransferase (PIMT). Mice deficient in PIMT accumulate isoAsp-containing proteins, resulting in cognitive deficits, abnormal neuronal physiology and cytoarchitecture, and fatal epileptic seizures 30-60 days after birth. Synapsins I and II, dynamin-1, collapsin response mediator protein 2 (CRMP2), and alpha/beta-tubulin are major targets of PIMT in brain. To investigate links between isoAsp accumulation and the neurological phenotype of the KO mice, we used Western blotting to compare patterns of in vivo phosphorylation or acetylation of the major PIMT targets listed above. Phosphorylations of synapsins I and II at Ser-9 were increased in female KO vs. WT mice, and acetylation of tubulin at Lys-40 was decreased in male KO vs. WT mice. Average levels of dynamin-1 phosphorylation at Ser-778 and Ser 795 were higher in male KO vs. WT mice, but the statistical significance (P>0.1) was low. No changes in phosphorylation were found in synapsins I and II at Ser 603, in CRMP2 at Ser-522 or Thr-514, in DARPP-32 at Thr-34, or in PDK1 at Ser 241. General levels of phosphorylation assessed with Pro-Q Diamond stain, or an anti-phosphotyrosine antibody, appeared similar in the WT and KO mice. We conclude that isoAsp accumulation is associated with altered functional status of several neuronal proteins that are highly susceptible to this type of damage. We also uncovered unexpected differences in how male and female mice respond to isoAsp accumulation in the brain. PMID- 24224060 TI - The exosome cofactor Rrp47 is critical for the stability and normal expression of its associated exoribonuclease Rrp6 in Saccharomyces cerevisiae. AB - Rrp6 is a conserved catalytic subunit of the eukaryotic nuclear exosome ribonuclease complex that functions in the productive 3' end maturation of stable RNAs, the degradation of transiently expressed noncoding transcripts and in discard pathways that eradicate the cell of incorrectly processed or assembled RNAs. The function of Rrp6 in these pathways is at least partially dependent upon its interaction with a small nuclear protein called Rrp47/Lrp1, but the underlying mechanism(s) by which Rrp47 functions in concert with Rrp6 are not established. Previous work on yeast grown in rich medium has suggested that Rrp6 expression is not markedly reduced in strains lacking Rrp47. Here we show that Rrp6 expression in rrp47? mutants is substantially reduced during growth in minimal medium through effects on both transcript levels and protein stability. Exogenous expression of Rrp6 enables normal levels to be attained in rrp47? mutants. Strikingly, exogenous expression of Rrp6 suppresses many, but not all, of the RNA processing and maturation defects observed in an rrp47? mutant and complements the synthetic lethality of rrp47? mpp6? and rrp47? rex1? double mutants. Increased Rrp6 expression in the resultant rrp47? rex1? double mutant suppresses the defect in the 3' maturation of box C/D snoRNAs. In contrast, increased Rrp6 expression in the rrp47? mpp6? double mutant diminishes the block in the turnover of CUTs and in the degradation of the substrates of RNA discard pathways. These results demonstrate that a principal function of Rrp47 is to facilitate appropriate expression levels of Rrp6 and support the conclusion that the Rrp6/Rrp47 complex and Rex1 provide redundant exonuclease activities for the 3' end maturation of box C/D snoRNAs. PMID- 24224062 TI - A prospective cohort study examining the associations of dietary calcium intake with all-cause and cardiovascular mortality in older Chinese community-dwelling people. AB - BACKGROUND: Most epidemiological studies of calcium intake and mortality risk have been conducted in populations with moderate to high calcium intake, and limited studies have focused on populations with low habitual calcium intake (i.e., mean dietary calcium intake <700 mg/d). OBJECTIVE: This study investigated the association between dietary calcium intake and death from all causes and cardiovascular disease in Chinese population with low habitual calcium intake. DESIGN: Data from 3,139 Chinese men and women in a population-based prospective cohort study, aged >=65 years and free of heart diseases or stroke at baseline, were analyzed. Primary outcome measures, identified from the death registry, were death from all causes and cardiovascular disease. Dietary calcium intake assessed using a validated food frequency questionnaire was categorized into sex-specific quartiles. Data on use of supplemental calcium (yes or no) including individual calcium supplements and other calcium containing supplement were collected. Cox regression models adjusted for demographic and lifestyle variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: During a median of 9.1 years of follow-up, 529 all-cause deaths (344 men, 185 women) and 114 (74 men, 40 women) deaths from cardiovascular disease were identified. An inverse trend between dietary calcium intake and mortality was observed. Compared with the lowest quartile (<458 mg/d for men, <417 mg/d for women), the highest quartile of dietary calcium intake (>762 mg/d for men, >688 mg/d for women) had a significantly reduced risk of all-cause mortality (multivariate HR=0.63, 95% CI=0.49-0.81, P(trend)<0.001) but an insignificant decreased risk of cardiovascular mortality (multivariate HR=0.70, 95% CI=0.41-1.21, P(trend)=0.228). Similar inverse association was observed when the analyses were stratified on calcium supplemental use. CONCLUSIONS: Higher intake of dietary calcium was associated with reduced risk of all-cause mortality and possibly cardiovascular mortality in Chinese older people with low habitual calcium intake. PMID- 24224063 TI - The role of the methyltransferase domain of bifunctional restriction enzyme RM.BpuSI in cleavage activity. AB - Restriction enzyme (REase) RM.BpuSI can be described as a Type IIS/C/G REase for its cleavage site outside of the recognition sequence (Type IIS), bifunctional polypeptide possessing both methyltransferase (MTase) and endonuclease activities (Type IIC) and endonuclease activity stimulated by S-adenosyl-L-methionine (SAM) (Type IIG). The stimulatory effect of SAM on cleavage activity presents a major paradox: a co-factor of the MTase activity that renders the substrate unsusceptible to cleavage enhances the cleavage activity. Here we show that the RM.BpuSI MTase activity modifies both cleavage substrate and product only when they are unmethylated. The MTase activity is, however, much lower than that of M1.BpuSI and is thought not to be the major MTase for host DNA protection. SAM and sinefungin (SIN) increase the Vmax of the RM.BpuSI cleavage activity with a proportional change in Km, suggesting the presence of an energetically more favorable pathway is taken. We further showed that RM.BpuSI undergoes substantial conformational changes in the presence of Ca(2+), SIN, cleavage substrate and/or product. Distinct conformers are inferred as the pre-cleavage/cleavage state (in the presence of Ca(2+), substrate or both) and MTase state (in the presence of SIN and substrate, SIN and product or product alone). Interestingly, RM.BpuSI adopts a unique conformation when only SIN is present. This SIN-bound state is inferred as a branch point for cleavage and MTase activity and an intermediate to an energetically favorable pathway for cleavage, probably through increasing the binding affinity of the substrate to the enzyme under cleavage conditions. Mutation of a SAM-binding residue resulted in altered conformational changes in the presence of substrate or Ca(2+) and eliminated cleavage activity. The present study underscores the role of the MTase domain as facilitator of efficient cleavage activity for RM.BpuSI. PMID- 24224064 TI - Surface-Enhanced Raman Spectroscopy of Polyelectrolyte-Wrapped Gold Nanoparticles in Colloidal Suspension. AB - The rapidly expanding field of surface-enhanced Raman spectroscopy (SERS) has helped fuel an intense interest in noble metal nanoparticle synthesis. An in suspension approach for quantifying SERS enhancement and relating that enhancement to a spontaneous Raman equivalent signal is described. Gold nanoparticles of various shapes were wrapped with polyelectrolyte multilayers that trapped Raman reporter molecules at defined distances from the metal core. Electrospray ionization liquid chromatography mass spectrometry (ESI-LC-MS) on digested samples was employed to measure the average number of bound Raman reporter molecules per gold nanoparticle, and inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the average number of gold atoms per nanoparticle. Using these data, SERS signal intensity was compared to a spontaneous Raman calibration curve to compute a spontaneous Raman equivalent factor. Three different geometries of gold nanoparticles (cubes, spheres, and trisoctahedra) were synthesized to investigate edge and corner effects using these quantitative techniques. Finite element method (FEM) electromagnetic simulations examined the relationship between the different geometries and the observed SERS signal intensities. The experimental observations and theoretical results indicate that cubic gold nanoparticles have the highest effective signal. PMID- 24224065 TI - U.S. Cigarette Demand: 1944-2004. PMID- 24224066 TI - Sociodemographic Factors Contribute to Mental Health Disparities and Access to Services Among Young Men Who Have Sex with Men in New York City. AB - Young men who have sex with men (YMSM) may be at increased risk for mental health problems including depression, post-traumatic stress (PTSD), and suicidality. The overriding goal of the current investigation was to examine mental health and mental health services in a diverse sample of YMSM. We analyzed cross-sectional data from a cohort study of 598 YMSM, including sociodemographics, mental health, and mental health care. We then tested for bivariate associations, and used multivariable modeling to predict depression, PTSD, suicidality and mental health care utilization. Lower socioeconomic status, unstable housing, and school non enrollment predicted depression and PTSD scores, while unstable housing and school non-enrollment predicted recent suicide attempt(s). These recent suicide attempt(s) also predicted current utilization of counseling or treatment, any history of psychiatric hospitalization, and any history of psychiatric diagnosis. Black and API men were less likely to have ever accessed mental health counseling or treatment. There were significant class-based differences with regard to mental health outcomes, but not mental health services. Further, recent crises (i.e., suicide attempt, hospitalization) were strong predictors of accessing mental health services. Improving the mental health of YMSM requires addressing the underlying structural factors that influence mental health outcomes and service access. PMID- 24224067 TI - The Gorbachev Anti-Alcohol Campaign and Russia's Mortality Crisis. AB - Political and economic transition is often blamed for Russia's 40% surge in deaths between 1990 and 1994. Highlighting that increases in mortality occurred primarily among alcohol-related causes and among working-age men (the heaviest drinkers), this paper investigates an alternative explanation: the demise of the 1985-1988 Gorbachev Anti-Alcohol Campaign. Using archival sources to build a new oblast-year data set spanning 1978-2000, we find a variety of evidence suggesting that the campaign's end explains a large share of the mortality crisis - implying that Russia's transition to capitalism and democracy was not as lethal as commonly suggested. PMID- 24224068 TI - A public-private partnership develops and externally validates a 30-day hospital readmission risk prediction model. AB - INTRODUCTION: Preventing the occurrence of hospital readmissions is needed to improve quality of care and foster population health across the care continuum. Hospitals are being held accountable for improving transitions of care to avert unnecessary readmissions. Advocate Health Care in Chicago and Cerner (ACC) collaborated to develop all-cause, 30-day hospital readmission risk prediction models to identify patients that need interventional resources. Ideally, prediction models should encompass several qualities: they should have high predictive ability; use reliable and clinically relevant data; use vigorous performance metrics to assess the models; be validated in populations where they are applied; and be scalable in heterogeneous populations. However, a systematic review of prediction models for hospital readmission risk determined that most performed poorly (average C-statistic of 0.66) and efforts to improve their performance are needed for widespread usage. METHODS: The ACC team incorporated electronic health record data, utilized a mixed-method approach to evaluate risk factors, and externally validated their prediction models for generalizability. Inclusion and exclusion criteria were applied on the patient cohort and then split for derivation and internal validation. Stepwise logistic regression was performed to develop two predictive models: one for admission and one for discharge. The prediction models were assessed for discrimination ability, calibration, overall performance, and then externally validated. RESULTS: The ACC Admission and Discharge Models demonstrated modest discrimination ability during derivation, internal and external validation post-recalibration (C-statistic of 0.76 and 0.78, respectively), and reasonable model fit during external validation for utility in heterogeneous populations. CONCLUSIONS: The ACC Admission and Discharge Models embody the design qualities of ideal prediction models. The ACC plans to continue its partnership to further improve and develop valuable clinical models. PMID- 24224069 TI - Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 months in a Goat Model. AB - OBJECTIVE: The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-D geometrical match between grafted and contralateral joints at 6 and 12 months after surgery. DESIGN: Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral Non-Operated joints were harvested at 6 and 12 months, and analyzed by indentation testing, micro-computed tomography, and histology to compare (1) histological indices of repair, (2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), (3) indentation stiffness, and (4) correlations between stiffness and 3-D structure. RESULTS: Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of Operated MFC were lower than Non-Operated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to Non-Operated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness. CONCLUSION: The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure. PMID- 24224071 TI - Vibrational Photoacoustic Tomography: Chemical Imaging beyond the Ballistic Regime. AB - Proof-of-concept of vibrational photoacoustic tomography is demonstrated with a homebuilt Raman laser generating greater than 100 mJ of energy per pulse at 1197 nm wavelength. We employed this system for excitation of second overtone transition of C-H bonds. Vibrational photoacoustic signal from C-H rich polyethylene tube phantom placed under 3 cm thick chicken breast tissue was obtained with a signal to noise ratio of 2.5. Further, we recorded photoacoustic image of a polyethylene ring placed under 5 mm chicken tissue with excellent contrast. This development opens new opportunities of performing label free vibrational imaging in the deep tissue regime. PMID- 24224070 TI - Does Posting Facebook Status Updates Increase or Decrease Loneliness? An Online Social Networking Experiment. AB - Online social networking is a pervasive but empirically understudied phenomenon. Strong public opinions on its consequences exist but are backed up by little empirical evidence and almost no causally-conclusive, experimental research. The current study tested the psychological effects of posting status updates on Facebook using an experimental design. For one week, participants in the experimental condition were asked to post more than they usually do, whereas participants in the control condition received no instructions. Participants added a lab "Research Profile" as a Facebook friend allowing for the objective documentation of protocol compliance, participants' status updates, and friends' responses. Results revealed (1) that the experimentally-induced increase in status updating activity reduced loneliness, (2) that the decrease in loneliness was due to participants feeling more connected to their friends on a daily basis and (3) that the effect of posting on loneliness was independent of direct social feedback (i.e. responses) by friends. PMID- 24224073 TI - Size reduction and radiation pattern shaping of multi-fed DCC slot antennas used in conformal microwave array hyperthermia applicators. AB - The use of conformal antenna array in the treatment of superficial diseases can significantly increase patient comfort while enhancing the local control of large treatment area with irregular shapes. Originally a regular square multi-fed slot antenna (Dual Concentric Conductor - DCC) was proposed as basic unit cell of the array. The square DCC works well when the outline of the treatment area is rectangular such as in the main chest or back area but is not suitable to outline diseases spreading along the armpit and neck area. In addition as the area of the patch increases, the overall power density decreases affecting the efficiency and thus the ability to deliver the necessary thermal dose with medium power amplifier (<50W). A large number of small efficient antennas is preferable as the disease is more accurately contoured and the lower power requirement for the amplifiers correlates with system reliability, durability, linearity and overall reduced cost. For such reason we developed a set of design rules for multi-fed slot antennas with irregular contours and we implemented a design that reduce the area while increasing the perimeter of the slot, thus increasing the antenna efficiency and the power density. The simulation performed with several commercial packages (Ansoft HFSS, Imst Empire, SemcadX and CST Microwave Studio) show that the size reducing method can be applied to several shapes and for different frequencies. The SAR measurements of several DCCs are performed using an in-house high resolution scanning system with tumor equivalent liquid phantom both at 915 MHz for superficial hyperthermia systems in US) and 433 MHz (Europe). The experimental results are compared with the expected theoretical predictions and both simulated and measured patterns of single antennas of various size and shapes are then summed in various combinations using Matlab to show possible treatment irregular contours of complex diseases. The local control is expected to significantly improve while maintaining the patient comfort. PMID- 24224072 TI - ATP Binding Cassette C1 (ABCC1/MRP1)-mediated drug efflux contributes to disease progression in T-lineage acute lymphoblastic leukemia. AB - PURPOSE: In acute lymphoblastic leukemia (ALL), multidrug resistance is often mediated by ATPase Binding Cassette (ABC) proteins, which principally involve ABCB1 (multidrug resistance 1, MDR1) and ABCC1 (multidrug resistance protein 1, MRP1). However, direct comparisons between the differential effects of ABCB1 and ABCC1 have been difficult, since identical cell lines with differential expression of these transporters have not been developed. EXPERIMENTAL DESIGN: In this study, we developed and compared the biological profiles of Jurkat cell lines that selectively over-expressed ABCB1 and ABCC1. Vincristine (VCR) plays an important role in the treatment of T-lineage ALL (T-ALL), and is often the first drug given to newly-diagnosed patients. Because of its importance in treatment, we provided escalating, sub-lethal doses of VCR to Jurkat cells, and extended our observations to expression profiling of newly diagnosed patients with T-ALL. RESULTS: We found that VCR-resistant cells over-expressed ABCC1 nearly 30-fold. The calcein AM assay confirmed that VCR-resistant cells actively extruded VCR, and that ABCC1-mediated drug resistance conferred a different spectrum of multidrug resistance than other T-ALL induction agents. siRNA experiments that blocked ABCC1 export confirmed that VCR resistance could be reversed in vitro. Analyses of T-lymphoblasts obtained from 92 newly diagnosed T-ALL patients treated on Children's Oncology Group Phase III studies 8704/9404 showed that induction failure could be explained in all but one case by the over-expression of ABCB1 or ABCC1. CONCLUSIONS: Taken together, these results suggest that over expression of ABC transporters plays a contributing role in mediating treatment failure in T-ALL, and underscore the need to employ alternate treatment approaches in patients for whom induction failed or for those with relapsed disease. PMID- 24224074 TI - Clinical Utility of Magnetic Resonance Thermal Imaging (MRTI) For Realtime Guidance of Deep Hyperthermia. AB - A critical need has emerged for volumetric thermometry to visualize 3D temperature distributions in real time during deep hyperthermia treatments used as an adjuvant to radiation or chemotherapy for cancer. For the current effort, magnetic resonance thermal imaging (MRTI) is used to measure 2D temperature rise distributions in four cross sections of large extremity soft tissue sarcomas during hyperthermia treatments. Novel hardware and software techniques are described which improve the signal to noise ratio of MR images, minimize motion artifact from circulating coupling fluids, and provide accurate high resolution volumetric thermal dosimetry. For the first 10 extremity sarcoma patients, the mean difference between MRTI region of interest and adjacent interstitial point measurements during the period of steady state temperature was 0.85 degrees C. With 1min temporal resolution of measurements in four image planes, this non invasive MRTI approach has demonstrated its utility for accurate monitoring and realtime steering of heat into tumors at depth in the body. PMID- 24224075 TI - Super-resolution method for arbitrary retrospective sampling in fluorescence tomography with raster scanning photodetectors. AB - Dense spatial sampling is required in high-resolution optical imaging and many other biomedical optical imaging methods, such as diffuse optical imaging. Arrayed photodetectors, in particular charge coupled device cameras are commonly used mainly because of their high pixel count. Nonetheless, discrete-element photodetectors, such as photomultiplier tubes, are often desirable in many performance-demanding imaging applications. However, utilization of the discrete element photodetectors typically requires raster scan to achieve arbitrary retrospective sampling with high density. Care must be taken in using the relatively large sensitive areas of discrete-element photodetectors to densely sample the image plane. In addition, off-line data analysis and image reconstruction often require full-field sampling. Pixel-by-pixel scanning is not only slow but also unnecessary in diffusion-limited imaging. We propose a super resolution method that can recover the finer features of an image sampled with a coarse-scale sensor. This generalpurpose method was established on the spatial transfer function of the photodetector-lens system, and achieved super-resolution by inversion of this linear transfer function. Regularized optimization algorithms were used to achieve optimized deconvolution. Compared to the uncorrected blurred image, the proposed super-resolution method significantly improved image quality in terms of resolution and quantitation. Using this reconstruction method, the acquisition speed with a scanning photodetector can be dramatically improved without significantly sacrificing sampling density or flexibility. PMID- 24224076 TI - Ball Lens Fiber Optic Sensor based Smart Handheld Microsurgical Instrument. AB - During freehand performance of vitreoretinal microsurgery the surgeon must perform precise and stable maneuvers that achieve surgical objectives and avoid surgical risk. Here, we present an improved smart handheld microsurgical tool which is based on a ball lens fiber optic sensor that utilizes common path swept source optical coherence tomography. Improvements include incorporation of a ball lens single mode fiber optic probe that increases the working angle of the tool to greater than 45 degrees; and increases the magnitude of the distance sensing signal through water. Also presented is a cutting function with an improved ergonomic design. PMID- 24224077 TI - Treatment compliance and effectiveness in complex PTSD patients with co-morbid personality disorder undergoing stabilizing cognitive behavioral group treatment: a preliminary study. AB - BACKGROUND: In the empirical and clinical literature, complex posttraumatic stress disorder (PTSD) and personality disorders (PDs) are suggested to be predictive of drop-out or reduced treatment effectiveness in trauma-focused PTSD treatment. OBJECTIVE: In this study, we aimed to investigate if personality characteristics would predict treatment compliance and effectiveness in stabilizing complex PTSD treatment. METHOD: In a randomized controlled trial on a 20-week stabilizing group cognitive behavioral treatment (CBT) for child-abuse related complex PTSD, we included 71 patients of whom 38 were randomized to a psycho-educational and cognitive behavioral stabilizing group treatment. We compared the patients with few PD symptoms (adaptive) (N=14) with the non adaptive patients (N=24) as revealed by a cluster analysis. RESULTS: We found that non-adaptive patients compared to the adaptive patients showed very low drop out rates. Both non-adaptive patients, classified with highly different personality profiles "withdrawn" and "aggressive," were equally compliant. With regard to symptom reduction, we found no significant differences between subtypes. Post-hoc, patients with a PD showed lower drop-out rates and higher effect sizes in terms of complex PTSD severity, especially on domains that affect regulation and interpersonal problems. CONCLUSIONS: Contrary to our expectations, these preliminary findings indicate that this treatment is well tolerated by patients with a variety of personality pathology. Larger sample sizes are needed to study effectiveness for subgroups of complex PTSD patients. PMID- 24224078 TI - Growing up in armed groups: trauma and aggression among child soldiers in DR Congo. AB - BACKGROUND: Child soldiers are often both victims and perpetrators of horrendous acts of violence. Research with former child soldiers has consistently shown that exposure to violence is linked to trauma-related disorders and that living in a violent environment is correlated with enhanced levels of aggression. OBJECTIVE: To gain more insight into the experiences and the mental health status of former child soldiers, we conducted a survey with N=200 former child soldiers and adult combatants in the DR Congo. METHODS: We conducted semi-structured interviews concerning military experiences, experienced and perpetrated violence, and mental health. RESULTS: Former child soldiers reported more experienced and perpetrated violence, a greater severity of trauma-related suffering, as well as higher appetitive aggression than adult ex-combatants. Appetitive aggression was related to more perpetrated violence, higher military ranks, voluntary recruitment and higher rates of reenlistments in former child soldiers. CONCLUSIONS: Our results indicate that growing up in an armed group is related to higher levels of trauma related disorders and aggressive behavior. This may explain the challenge of reintegrating former child soldiers. It is thus important to consider mental health problems, particularly trauma-related disorders and aggressive behavior, of former child soldiers for designing adequate reintegration programs. PMID- 24224079 TI - A Hierarchical Distance Sampling Approach to Estimating Mortality Rates from Opportunistic Carcass Surveillance Data. AB - Distance sampling is widely used to estimate the abundance or density of wildlife populations. Methods to estimate wildlife mortality rates have developed largely independently from distance sampling, despite the conceptual similarities between estimation of cumulative mortality and the population density of living animals. Conventional distance sampling analyses rely on the assumption that animals are distributed uniformly with respect to transects and thus require randomized placement of transects during survey design. Because mortality events are rare, however, it is often not possible to obtain precise estimates in this way without infeasible levels of effort. A great deal of wildlife data, including mortality data, is available via road-based surveys. Interpreting these data in a distance sampling framework requires accounting for the non-uniformity sampling. Additionally, analyses of opportunistic mortality data must account for the decline in carcass detectability through time. We develop several extensions to distance sampling theory to address these problems.We build mortality estimators in a hierarchical framework that integrates animal movement data, surveillance effort data, and motion-sensor camera trap data, respectively, to relax the uniformity assumption, account for spatiotemporal variation in surveillance effort, and explicitly model carcass detection and disappearance as competing ongoing processes.Analysis of simulated data showed that our estimators were unbiased and that their confidence intervals had good coverage.We also illustrate our approach on opportunistic carcass surveillance data acquired in 2010 during an anthrax outbreak in the plains zebra of Etosha National Park, Namibia.The methods developed here will allow researchers and managers to infer mortality rates from opportunistic surveillance data. PMID- 24224080 TI - A photoisomerization-coupled asymmetric Stetter reaction: application to the total synthesis of three diastereomers of (-)-cephalimysin A. AB - The total synthesis of 8-epi, 8,9-epi, and 9-epi-(-)-cephalimysin A is described. Our catalytic enantioselective synthesis takes advantage of a novel tandem photoisomerization/Stetter reaction. The approach provides rapid access to the desired spirofuranone lactam core in good yield and excellent enantioselectivity. A late stage oxidation strategy allows for flexible access to three of the four diastereomers of cephalimysin A. Access to the epimers provides further support for the correction of the initially proposed relative stereochemistry of cephalimysin A. PMID- 24224081 TI - Halogen Photoelimination from Dirhodium Phosphazane Complexes via Chloride Bridged Intermediates. AB - Halogen photoelimination is a critical step in HX-splitting photocatalysis. Herein, we report the photoreduction of a pair of valence-isomeric dirhodium phosphazane complexes, and suggest that a common intermediate is accessed in the photochemistry of both mixed-valent and valence-symmetric complexes. The results of these investigations suggest that halogen photoelimination proceeds by two sequential photochemical reactions: ligand dissociation followed by subsequent halogen elimination. PMID- 24224082 TI - Controllably degradable beta-sheet nanofibers and gels from self-assembling depsipeptides. AB - Self-assembled peptide materials have received considerable interest for a range of applications, including 3D cell culture, tissue engineering, and the delivery of cells and drugs. One challenge in applying such materials within these areas has been the extreme stability of beta-sheet fibrillized peptides, which are resistant to proteolysis, degradation, and turnover in biological environments. In this study, we designed self-assembling depsipeptides containing ester bonds within the peptide backbone. Beta-sheet fibrillized nanofibers were formed in physiologic conditions, and two of these nanofiber-forming depsipeptides produced hydrogels that degraded controllably over the course of days-to-weeks via ester hydrolysis. With HPLC, TEM, and oscillating rheometry, we show that the rate of hydrolysis can be controlled in a straightforward manner by specifying the amino acid residues surrounding the ester bond. In 3D cell cultures, depsipeptide gels softened over the course of several days and permitted considerably more proliferation and spreading of C3H10T1/2 pluripotent stem cells than non degradable analogs. This approach now provides a reliable and reproducible means to soften or clear beta-sheet fibrillized peptide materials from biological environments. PMID- 24224083 TI - Polymer-Protein Hydrogel Nanomatrix for Stabilization of Indocyanine Green towards Targeted Fluorescence and Photoacoustic Bio-imaging. AB - Indocyanine green (ICG) is an optical contrast agent commonly used for a variety of imaging applications. However, certain limitations of the free dye molecule, concerning its low stability, uncontrolled aggregation and lack of targeting ability, have limited its use. Presented here is a method of embedding ICG in a novel polymer/protein hybrid nanocarrier so as to overcome the above inherent drawbacks of the free molecule. The hybrid nanocarrier consists of a non-toxic and biocompatible polyacrylamide nanoparticle (PAA NP) matrix that incorporates human serum albumin (HSA). This nanocarrier was synthesized through pre conjugation with HSA and amine functionalized monomer, followed by polymerization using biodegradable cross-linkers, in a water-in-oil emulsion. The ICG dye is loaded into the HSA conjugated PAA nanoparticles (HSA-PAA NPs) through post loading. Compared to the PAA polymer matrix, the presence of hydrophobic pockets in the HSA-PAA NPs further increases the chemical and physical stability of ICG. This is manifested by lowering the chemical degradation rates under physiological conditions, as well as by improving the thermal- and photo-stability of the dye. A targeting moiety, F3-Cys peptide, was attached to the surface of the NPs, for selective delivery to specific cancer cell lines. The suitability of these NPs for optical imaging applications was demonstrated by performing fluorescence imaging on a rat gliosarcoma cell line (9L). We also present the photoacoustic response of the HSA-PAA NPs, used as imaging contrast agents, in the spectral window of 700 nm to 800 nm. PMID- 24224084 TI - Angiotensin II Stimulates Sympathetic Neurotransmission to Adipose Tissue. AB - Angiotensin II (AngII) facilitates sympathetic neurotransmission by regulating norepinephrine (NE) synthesis, release and uptake. These effects of AngII contribute to cardiovascular control. Previous studies in our laboratory demonstrated that chronic AngII infusion decreased body weight of rats. We hypothesized that AngII facilitates sympathetic neurotransmission to adipose tissue and may thereby decrease body weight. The effect of chronic AngII infusion on the NE uptake transporter and NE turnover was examined in metabolic (interscapular brown adipose tissue, ISBAT; epididymal fat, EF) and cardiovascular tissues (left ventricle, LV; kidney) of rats. To examine the uptake transporter saturation isotherms were performed using [3H]nisoxetine (NIS). At doses that lowered body weight, AngII significantly increased ISBAT [3H]NIS binding density. To quantify NE turnover, alpha-methyl-para-tyrosine (AMPT) was injected in saline-infused, AngII-infused, or saline-infused rats that were pair-fed to food intake of AngII-infused rats. AngII significantly increased the rate of NE decline in all tissues compared to saline. The rate of NE decline in EF was increased to a similar extent by AngII and by pair-feeding. In rats administered AngII and propranolol, reductions in food and water intake and body weight were eliminated. These data support the hypothesis that AngII facilitates sympathetic neurotransmission to adipose tissue. Increased sympathetic neurotransmission to adipose tissue following AngII exposure is suggested to contribute to reductions in body weight. PMID- 24224085 TI - Podocalyxin regulates pronephric glomerular development in zebrafish. AB - Vertebrate glomerular podocytes possess a highly sialylated transmembrane glycoprotein, Podocalyxin. In mammals, the sialic acid of Podocalyxin plays a crucial role in the formation of the characteristic podocyte architecture required for glomerular filtration. We examined the function of Podocalyxin in the developing zebrafish pronephros by disrupting the expression of podocalyxin through the use of morpholino antisense oligonucleotides. Podocalyxin was localized at the apical membrane of podocytes throughout pronephric glomerular development in zebrafish. Translational blocking of podocalyxin expression resulted in pericardial edema and a hypoplastic glomerulus. Whereas regular foot processes with a slit diaphragm covered 66.7 +/- 7.8% of the urinary surface of glomerular basement membrane in control fish, only 14.4 +/- 7.5% of this area was covered with regular foot processes in the translationally-blocked morphants. Splice blocking of podocalyxin exon 2, which partially encodes the bulky mucin domain with extensive sialic acid-containing sugar chains, resulted in the deletion of 53% of mucin domain-coding sequence from podocalyxin mRNA. Approximately 40% of these splice-blocked morphants had mild pericardial edema. Although the pronephric glomerulus in the splice-blocked morphants exhibited almost normal appearance with developed glomerular capillaries and mesangium, they had only 36.3 +/- 6.9% of the area covered with regular foot processes. In conclusion, Podocalyxin is predominantly expressed in the podocytes and plays a distinct role in the formation of the podocyte foot processes with a slit diaphragm during zebrafish pronephric development. PMID- 24224086 TI - Migraine and Despair: Factors Associated with Depression and Suicidal Ideation among Canadian Migraineurs in a Population-Based Study. AB - This study sought to (1) investigate the association between migraine and both depression and suicidal ideation and (2) to identify the factors independently associated with each of these mental health problems among Canadian men and women with migraine. Data were analyzed from the 2005 Canadian Community Health Survey (CCHS). Presence of migraine was assessed by self-report of a health professional diagnosis. Current depression was measured using the CIDI-SF, and suicidal ideation was based on a question about serious consideration of suicide at any point during the respondent's lifetime. Migraineurs were found to have elevated odds of depression (men: OR = 2.02; 95% CI = 1.70, 2.41; women: OR = 1.89; 95% CI = 1.71, 2.10) and suicidal ideation (men: OR = 1.70; 95% CI = 1.55, 1.96; women: OR = 1.72; 95% CI = 1.59, 1.86) even when adjusting for sociodemographic variables and disability status. The odds of depression and suicidal ideation were higher among both genders of migraineurs who were younger, unmarried and had more activity limitations; associations with poverty and race depended on gender and whether the focus was on depression or suicidal ideation. While screening for depression is already recommended for those with migraine, this research helps identify which migraineurs may require more immediate attention, including those who are younger, unmarried, and experiencing limitations in their activities. PMID- 24224087 TI - Detection and Isolation of Airborne Influenza A H3N2 Virus Using a Sioutas Personal Cascade Impactor Sampler. AB - The air we breathe contains microorganisms that can cause infectious respiratory diseases. After two occupants of an apartment were diagnosed with influenza in February of 2013, efforts were made to detect and isolate airborne influenza virus using two different types of active air samplers: a Sioutas Personal Cascade Impactor Sampler (PCIS) and an SKC BioSampler. The PCIS collects size fractionated particles by impaction on polytetrafluoroethylene filters, whereas the SKC BioSampler collects airborne particles in liquid media. Influenza H3N2 virus was collected by both types of air samplers. The PCIS collected a range of particle sizes containing influenza virus near one of the sick individuals but only ultrafine particles when the samplers were positioned farther away. Viable virus was present in the liquid collection media of the SKC BioSampler and some PCIS filters. These findings suggest that influenza patients produce ultrafine aerosol particles that contain viable virus. PMID- 24224088 TI - Effects of mild and severe knee joint pain on various activities of daily living in the female elderly. AB - This study aimed to examine the differences in the ability to perform various activities of daily living (ADLs) among groups with various knee problems. The participants consisted of 328 elderly females (age 60-94; mean age 76.1 years; standard deviation 6.2). The subjects were classified into three groups: those without knee pain, those with mild knee pain, and those with severe knee pain. ADLs with markedly higher (>97%) and lower (<38%) achievement rates in the group without knee pain were not significantly different among the three groups. Achievement rates of 40%-97% for ADLs were significantly lower in the group with severe knee pain than in the group without knee pain. In addition, the groups with mild and severe knee pain demonstrated significantly lower achievement rates of ascending and descending stairs and sitting up than the group without knee pain. In conclusion, regardless of the presence of absence of mild or severe knee pain, some ADLs are difficult to achieve, while others are easy. The elderly with severe knee pain find it difficult to achieve many ADLs. In addition, it is difficult for the elderly with mild and severe knee pain to ascend and descend stairs and to sit up. PMID- 24224089 TI - Effectiveness of methylcobalamin and folinic Acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. AB - Treatments targeting metabolic abnormalities in children with autism are limited. Previously we reported that a nutritional treatment significantly improved glutathione metabolism in children with autistic disorder. In this study we evaluated changes in adaptive behaviors in this cohort and determined whether such changes are related to changes in glutathione metabolism. Thirty-seven children diagnosed with autistic disorder and abnormal glutathione and methylation metabolism were treated with twice weekly 75 ug/Kg methylcobalamin and twice daily 400 ug folinic acid for 3 months in an open-label fashion. The Vineland Adaptive Behavior Scale (VABS) and glutathione redox metabolites were measured at baseline and at the end of the treatment period. Over the treatment period, all VABS subscales significantly improved with an average effect size of 0.59, and an average improvement in skills of 7.7 months. A greater improvement in glutathione redox status was associated with a greater improvement in expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills. Age, gender, and history of regression did not influence treatment response. The significant behavioral improvements observed and the relationship between these improvements to glutathione redox status suggest that nutritional interventions targeting redox metabolism may benefit some children with autism. PMID- 24224090 TI - Factors Associated with Women's Chronic Disease Management: Associations of Healthcare Frustrations, Physician Support, and Self-Care Needs. AB - Previous research emphasizes the importance of reducing healthcare frustrations and enhancing physician supports to help patients engage in recommended healthcare regimens. However, less is known about how these factors are associated with aging women's knowledge about self-care behavior. This study examined the sociodemographics, health indicators, healthcare-related frustrations, and perceptions of physician support associated with middle-aged and older adult females' self-reported need for help to learn how to take better care of their health. Data were analyzed from 287 females with one or more chronic conditions who completed The National Council on Aging (NCOA) Chronic Care Survey. A logistic regression model was developed. Women who were non-White (OR = 2.26, P = 0.049) were more likely to need help learning how to better manage their health. Those who had some college education or more (OR = 0.55, P = 0.044) and lower healthcare-related frustrations (OR = 0.44, P = 0.017) and perceived to have more physician support (OR = 0.49, P = 0.033) were less likely to need help learning how to better manage their health. Findings can inform the planning, implementation, assessment, and dissemination of evidence-based self management programs for middle-aged and older women within and outside of clinical settings. PMID- 24224091 TI - Evaluation of Mallotus oppositifolius Methanol Leaf Extract on the Glycaemia and Lipid Peroxidation in Alloxan-Induced Diabetic Rats: A Preliminary Study. AB - Objective. Mallotus oppositifolius (Geiseler) Mull. Arg. (Euphorbiaceae) is folklorically used to "treat" diabetic conditions in some parts of Nigeria therefore the study, to investigate the extract of the leaves for activities on hyperglycaemia, lipid peroxidation, and increased cholesterol levels in vivo in alloxan diabetic rats as well as its potential antioxidant activity in vitro. Methods. Albino rats (240-280 g) were given an injection of 120 mg/kg body weight, i.p. of alloxan monohydrate. After 8 days, diabetic animals with elevated fasting blood glucose levels (>9 mmol/L) were considered and selected for the study. Results. Oral treatment with the extract administered every 12 h by gavage at doses of 100, 200, and 400 mg/kg of the extract to the test rats, for 14 days, resulted in a significant dose-dependent decrease in blood glucose levels from 12.82 +/- 1.02 mmol/dL to 4.92 +/- 2.01 mmol/dL at the highest dose of 400 mg/kg compared to the control drug and glibenclamide as well as attendant significant decline in diabetic rats employed in the study. Conclusion. The extract also showed in vitro concentration-dependent antioxidant activity following the 1,1 diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing assays. Findings further suggest the presence of active antidiabetic and antioxidant principles in M. oppositifolius leaves. PMID- 24224092 TI - Relationship of sternal foramina to vital structures of the chest: a computed tomographic study. AB - Sternal foramina are a well-known variant anatomy of the sternum and carry the risk of life-threatening complications like pneumothorax or even pericardial/cardial punction during sternal biopsy or acupuncture. There have been numerous studies numerous studies examinimg prevalence of sternal foramina, but the study of the exact anatomical relationship to intrathoracic structures has received little attention. In a retrospective study of 15 patients with sternal foramina, the topographical anatomy in respect to vital chest organs was examined. In most patients, the directly adjacent structure was the lung (53.3%) or mediastinal fat (33.3%). Only in three patients, the heart was located directly adjacent to a sternal foramen (20%). Theoretically, if the needle is inserted deep enough it will at some point perforate the pericardium in all examined patients. There was no correlation between the patient habitus (i.e., thickness of the subcutaneous fat) and the distance to a vital organ. In this sample, pericardial punction would have not occured if the needle is not inserted deeper than 2.5 cm. Given the preliminary nature of the data, general conclusions of a safe threshold for needle depth should be made with caution. To minimize the risk of hazardous complications, especially with sternal biopsy, preprocedural screening or image guidance is advocated. PMID- 24224093 TI - Interaction of Normal and Sickle Hemoglobins for Sodium Dodecylsulphate and Hydrogen Peroxide at pH 5.0 and 7.2. AB - Clinical manifestations of malaria primarily result from proliferation of the parasite within the hosts' erythrocytes. The malaria parasite digests hemoglobin within its digestive vacuole through a sequential metabolic process involving multiple proteases. The activities of these proteases could lead to the production of ROS which could lead to the death of the parasites due to the destruction of their membrane. The action of SDS on hemoglobins can be likened to the way malarial proteases destabilizes host hemoglobin. Hence, the study was designed to determine the binding parameters of SDS and H2O2 for normal, sickle trait carrier and sickle hemoglobins at pH 5.0 and 7.2 using UV-VIS Titration Spectrophotometry. Hb-SDS interactions were significantly different at pH 5.0 but were not at pH 7.2. Also, Hb-H2O2 interactions were statistically different at pH 5.0 and 7.2. The interactions suggest that HbA and HbS are easily destabilized than HbAS and that HbAS has more affinity for H2O2. These suggest a production of more ferryl intermediates or hydroxyl radicals. All these interactions may hinder the development of the malaria parasite at the intraerythrocytic stage and could likely account for a significant proportion of the mechanism that favours the resistance to malaria by individuals with HbAS. PMID- 24224095 TI - Improving compliance with screening of diabetic patients for microalbuminuria in primary care practice. AB - Studies showed suboptimal compliance rate of primary care physicians with microalbuminuria screening. This study evaluated impact of electronic medical records (EMR) and computerized physicians reminders on compliance rate and showed small to modest improvement. Combining EMR with quality control monitoring has significantly improved compliance [OR 1.556, 95% CI 1.251-1.935, P = 0.006]. PMID- 24224094 TI - Risk of cancer in diabetes: the effect of metformin. AB - Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge. PMID- 24224096 TI - Ethnic Background and Overweight among 5-Year-Old Children: The "Be Active, Eat Right" Study. AB - Introduction. This study investigates the association between ethnic background and overweight (obesity included) among 5 year olds. Methods. We used baseline data from 5 year olds (n = 7801) and their parents collected for the "Be active, eat right" study. A child was considered to be of non-Dutch ethnic background when at least one of the parents was born abroad. Odds ratios (ORs) were adjusted for sociodemographic characteristics. Results. Compared to children of Dutch ethnic background, for children with a Moroccan ethnic background the OR for being overweight (obesity included) was 2.27 (95% CI 1.48-3.47), for Turkish children the OR was 3.63 (95% confidence interval (CI) 2.46-5.35), for Antillean children the OR was 1.97 (95% CI 1.01-3.86), and for Surinamese children the OR was 0.47 (95% CI 0.20-1.06). Addition of parental overweight decreased the ORs for Moroccan and Turkish children by 10.2% and 12.5%, and addition of watching TV and having breakfast by the child decreased the ORs by 7.9% and 12.2%. Conclusion. Already at a young age, children of Moroccan and Turkish ethnic background are at increased risk for being overweight compared to Dutch children. Parental overweight, watching TV, and not having breakfast by the child are contributing factors in this association. PMID- 24224097 TI - Cognitive Dysfunction and Dementia in Primary Sjogren's Syndrome. AB - Background. Primary Sjogren's syndrome (PSS) is a frequent systemic autoimmune disease. In this study, we aimed to explore the cognitive impairment and the correlations with brain MRI. Methods. Twenty-five patients (mean age 55 +/- 11.8 years, 21 females) with PSS were prospectively selected and tested with a French translation of the Brief Repeatable Battery for Neuropsychological Examination. The results were compared with the scores for 25 matched patients with multiple sclerosis (MS) and 25 controls. Brain lesions were assessed by brain MRI using the Wahlund classification. Results. Fifteen of the 25 PSS patients (60%) presented with cognitive disorders versus 19/25 MS patients (76%). Five patients had dementia in the PSS group. Speed of information processing, attention, immediate and long-term memory, and executive functions were frequently impaired. The mean duration of cognitive complaints was 5.6 +/- 6.1 years, and the mean duration of PSS was 15.8 +/- 14.0 years. A trend towards a correlation was found between the severity of cognitive impairment and the degree of white matter lesions (WML) (P = 0.03, rho = 0.43). Conclusion. Cognitive impairment-mild or dementia-exists in patients with PSS. Further MRI studies are needed to better understand the precise neural basis of cognitive impairment in PSS patients. PMID- 24224098 TI - Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of beta -Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity. AB - Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2 dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of beta -glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of beta glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of beta -glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level. PMID- 24224099 TI - Better survival with three-dimensional conformal radiotherapy than with conventional radiotherapy for cervical cancer: a population-based study. AB - Three-dimensional conformal radiation therapy (3DCRT) has emerged as a preferred treatment for gynecologic malignancies. Yet its superiority to conventional radiotherapy (2-dimensional radiotherapy (2DRT)) for gynecologic malignancies has not been well established. Data from the 2005 to 2010 National Health Insurance Research Database (NHIRD) provided by the National Research Institutes in Taiwan were analyzed to address this issue. Patients were initially diagnosed as having cervical cancer according to the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 180, and this clinical diagnosis was confirmed histopathologically or cytologically. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the reported data. Between January 2005 and December 2010, there were 776 patients with newly diagnosed cervical cancer without metastasis, local recurrence, or surgical treatment before RT and 132 and 644 patients, respectively, who received 2DRT and 3DCRT. After adjustment for age, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, side effects, urbanization level, geographic region, and enrollee category in the 5-year follow-up period, the HR was 1.82 (95% CI, 1.16 2.85, P = 0.009). The 5-year survival rate in the 2DRT and 3DCRT groups was 73.0% and 82.3%, P = 0.007, respectively. Cervical cancer patients treated with 3DCRT had better overall survival. PMID- 24224101 TI - Postthyroidectomy throat pain and swallowing: do proton pump inhibitors make a difference? AB - Objectives. Following thyroid surgery patients complain from swallowing disability and throat pain resembling symptoms of laryngopharyngeal reflux (LPR). The purpose of this study is to assess whether proton pump inhibitors (PPIs) given to patients in the first postoperative week relieve the swallowing disability and throat pain complaints. Materials and Methods. A questionnaire was given to 523 patients who had thyroid surgery between October 2010 and August 2011. In the first postoperative clinic visit each patient was approached to fill out a questionnaire. 208 patients met criteria, 100 of which were on PPIs (study group) and 108 were not on PPIs (control group). Results. When comparing the study group to the control group, the average pain level was 2.57 compared to 3.9 during the first postoperative week, and 1.27 compared to 2.41 at day 7 (P value = 0.001). Swallowing disability was also lower in the study group when compared to the control group, 1.87 and 3.12, respectively, during the first postoperative week and 0.87 and 1.76, respectively, at day 7 (P value = 0.007). Conclusion. Patients treated with PPIs had less pain and swallowing disability in the first week following thyroid surgery, when compared to patients not treated with PPIs. PMID- 24224100 TI - The Chemokine CXCL8 in Carcinogenesis and Drug Response. AB - Although the functions of chemokines in the regulation of immune processes have been studied in some detail, the role of these biomolecules in cancer is not fully understood. Chemokines mediate migration of immune cells and other functions related to immunity. They are also involved in oncogenesis and in tumor progression, invasion, and metastasis through mechanisms similar to their roles in immune functions. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. Consequently, chemokines and their receptors present potential therapeutic targets for anticancer drugs. The chemokine CXCL8, also known as interleukin-8 (IL8), is a proinflammatory molecule that has functions within the tumor microenvironment. Due to its potent angiogenic effects and the activity of the chemokine and its receptors in the promotion of invasion and metastasis, CXCL8 and its receptors are now considered as attractive targets for cancer therapy. This review relates the current understanding of the regulation, signaling, and functions of CXCL8 that contribute to tumor growth and metastasis, and of its role in drug response. PMID- 24224103 TI - Validation of simultaneous volumetric and HPLC methods for the determination of pridinol mesylate in raw material. AB - Simple, sensitive, and economical simultaneous volumetric and HPLC methods for the determination of pridinol mesylate in raw material have been developed. The volumetric method is based on the reaction of pridinol with sodium lauryl sulphate in diluted sulphuric acid. Dimethyl yellow was used as indicator to detect the end point of the titration in aqueous/organic layer. The HPLC method for the determination of pridinol mesylate employs a reverse phase C18 column at ambient temperature with a mobile phase consisting of acetonitrile: 0.05 M potassium dihydrogen phosphate, pH adjusted to 5.0 (1 : 2, v/v). The flow rate was 0.8 mL/min. Quantitation was achieved with UV detection at 258 nm based on peak area. Both methods were found to be suitable for the quality control of pridinol mesylate in raw material. PMID- 24224104 TI - Ameloblastomatous CCOT: A Case Report of a Rare Variant of CCOT with a Review of the Literature on Its Diverse Histopathologic Presentation. AB - Calcifying odontogenic cyst is considered as a rare lesion and accounts for 1% of jaw cysts. It represents a heterogeneous group of lesions which exhibit a variety of clinicopathologic and behavioral features. It has been categorized as cyst and neoplasm. Even after several classification and subclassification, COC remains an enigma. WHO classification 2005 has reclassified the lesion as calcifying cystic odontogenic tumor (CCOT). Ameloblastomatous COC is a rare variant which is not much described in the literature. This report describes one such case which was large multicystic, involved the coronoid and condylar process of the mandible, and treated by subhemimandibulectomy. The case was recurrence free even after 1 year of followup. PMID- 24224105 TI - Transient hiccups associated with oral dexamethasone. AB - Hiccups, or singulata (hiccup is singultus), are commonly experienced by most people at one time or another and are usually brief and self-limiting. Although pharmacotherapeutic agents are not generally considered causal in the etiology of hiccups, many clinicians empirically associate episodic hiccups in their patients as being drug induced. The two classes of drugs most often cited as causing hiccups are corticosteroids and benzodiazepines. This report involved a patient who was given preoperative dexamethasone and developed hiccups before anesthesia and surgery commenced. He at no time was in distress, and the surgical procedure was completed without complication. By the second postsurgical day his hiccups were resolved completely. Although the association may be anecdotal, many clinicians consider hiccups a potential side effect of steroid therapy, especially high doses of steroids. Of interest in this case is the relatively low dose of corticosteroid used, albeit apparently linked to his hiccups. Practitioners should be aware of this potential condition. PMID- 24224106 TI - Chronic Eosinophilic Leukemia-Not Otherwise Specified (NOS) in the Background of a Large Cell Lymphoma. AB - Clonal eosinophilic disorders are rare among hematological malignancies. Most eosinophilia tends to be due to secondary causes such as infections, hypersensitivity conditions, drug reactions, and connective tissue disorders. The presence of a primary clonal eosinophilic disorder such as chronic eosinophilic leukemia-not otherwise specified (NOS) in the presence of a synchronous large cell lymphoma-is rare making the diagnosis challenging. We present a case of a 51 year-old female with the aforementioned presentation and demonstrate the extensive workup performed to identify the diagnosis. PMID- 24224107 TI - Pitfalls in the diagnosis of anaplastic large cell lymphoma with a small cell pattern. AB - Anaplastic large cell lymphoma with a small cell pattern is a rare T-cell lymphoma. This condition is more frequently seen in younger patients and should be considered when patients present with leucocytosis and constitutional symptoms. In this report, we describe our diagnostic work-up for one such case using blood, lymph node, and bone marrow aspirate samples, highlighting the variability of antigen expression seen in different sample types and methodologies. This case shows the importance of having a high index of suspicion and assessing CD30 and anaplastic lymphoma kinase expression in all suspected T cell neoplasms even though this rare condition is not necessarily expected. PMID- 24224102 TI - Ionotropic glutamate receptors and voltage-gated Ca2+ channels in long-term potentiation of spinal dorsal horn synapses and pain hypersensitivity. AB - Over the last twenty years of research on cellular mechanisms of pain hypersensitivity, long-term potentiation (LTP) of synaptic transmission in the spinal cord dorsal horn (DH) has emerged as an important contributor to pain pathology. Mechanisms that underlie LTP of spinal DH neurons include changes in the numbers, activity, and properties of ionotropic glutamate receptors (AMPA and NMDA receptors) and of voltage-gated Ca2+ channels. Here, we review the roles and mechanisms of these channels in the induction and expression of spinal DH LTP, and we present this within the framework of the anatomical organization and synaptic circuitry of the spinal DH. Moreover, we compare synaptic plasticity in the spinal DH with classical LTP described for hippocampal synapses. PMID- 24224108 TI - Anomalous origin of left coronary artery from the pulmonary trunk in a mildly symptomatic adult female. AB - Anomalous origin of the left coronary artery from the pulmonary trunk, also known as Garland-Bland-White syndrome, is an extremely rare but potentially fatal congenital cardiovascular anomaly, and it often exists as an isolated condition. We hereby report an adult female who was admitted for mild chest discomfort and was accidentally diagnosed to have anomalous origin of the left coronary artery from the pulmonary trunk. This anomaly was simply repaired by using a bovine pericardial patch to obliterate the anomalous opening in the pulmonary trunk and a single coronary artery bypass graft. This report highlights the characteristic events of the anomaly in an adult with only mild symptoms. PMID- 24224109 TI - Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction. AB - Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed. PMID- 24224110 TI - Onyx Embolization of Ruptured Intracranial Aneurysm Associated with Behcet's Disease. AB - Introduction. Intracranial aneurysms associated with Behcet's disease (BD) are a rare occurrence. They are fragile, thin-walled pseudoaneurysms, which have high tendency to rupture and present a therapeutic challenge. Case Presentation. We report a 26-year-old male with BD presented with subarachnoid hemorrhage due to ruptured middle cerebral artery aneurysm. Additionally, two unruptured aneurysms were identified. He underwent endovascular embolization using Onyx with successful obliteration of the ruptured aneurysm. Medical therapy resulted in regression of one and resolution of the other aneurysms. Conclusion. We describe the first report of the application of Onyx for obliteration of ruptured cerebral aneurysm in BD as a feasible and safe therapeutic option for patients who are not candidates for other techniques. PMID- 24224111 TI - Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer's disease. AB - We are in the midst of an epidemic of Alzheimer's disease (AD) in developed countries. We have postulated that ingestion of inorganic copper from drinking water and taking supplement pills and a high fat diet are major causative factors. Ingestion of inorganic copper can directly raise the blood free copper level. Blood free copper has been shown by the Squitti group to be elevated in AD, to correlate with cognition, and to predict cognition loss. Secondly, we have shown that AD patients are zinc deficient compared to age matched controls. Zinc is important in neuronal protection. We carried out a 6-month small double blind trial of a new zinc formulation on AD patients. We found that in patients 70 years and older, zinc therapy protected against cognition decline compared to placebo controls. We also found that zinc therapy significantly lowered blood free copper levels. So zinc efficacy could be due to restoring neuronal zinc levels, to lowering blood free copper levels, or to both. PMID- 24224112 TI - Combined treatment with Myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. AB - Background. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis, is the most common form of thyroiditis affecting more than 10% of females and 2% of males. The present study aims to evaluate the beneficial effect of a combined treatment, Myo-Inositol plus selenomethionine, on subclinical hypothyroidism. Methods. The study was designed as a double-blind randomized controlled trial. Eligible patients were women diagnosed with subclinical hypothyroidism having Tg antibodies (TgAb) titer higher than 350 IU/mL. Outcome measures were Thyroid Stimulating Hormone (TSH) levels, thyroid peroxidase antibodies (TPOAb) and TgAb titer, selenium, and Myo Inositol plasma concentration. Results. In the present paper, we demonstrated that the beneficial effects obtained by selenomethionine treatment on patients affected by subclinical hypothyroidism, likely due to the presence of autoantibody (TPOAb and TgAb), are further improved by cotreatment with Myo Inositol. Conclusions. Indeed, due to its action as TSH second messenger, Myo Inositol treatment reduces TSH levels closer to physiological concentrations. PMID- 24224113 TI - Clinicopathological study of 25 cases of diverticular disease of the appendix: experience from farwaniya hospital. AB - Background. Diverticular disease of the appendix (DDA) is a rare disease and it has been shown to be associated with locoregional neoplasms. This study was conducted to characterize clinicopathological features and to investigate its association with appendiceal neoplasms. Methods. We searched the records of the Department of Pathology at Farwaniya Hospital for cases of diverticular disease of the appendix between 2003 and 2011. Histological slides and patient charts were reviewed for relevant information. Consecutive cases of acute appendicitis were selected as a control group. Results. We identified 25 cases of DDA, 24 of which occurred in men. Mean age of DDA patients was 35 +/- 10.1 years and was significantly greater than that of appendicitis patients (P = 0.027). The mean temperature of cases (37.9 degrees ) was significantly higher (P = 0.012) than that of the controls (37.3 degrees ). The cases had lower white blood cell (WBC) counts compared to controls (13.6 versus 16.7, P = 0.04). Pathological diagnosis identified 4 cases of diverticulosis, 5 cases of diverticulitis, 6 cases of diverticulosis with acute appendicitis, and 10 cases of diverticulitis and appendicitis. None of the cases was associated with any type of neoplasm. Conclusions. DDA is a rare disease, and clinicians and radiologists should be aware of it. Male sex and adult age seem to be risk factors associated with DDA. The disease may not have any direct association with any neoplasm. PMID- 24224114 TI - Evaluation of Artemisia amygdalina D. for Anti-Inflammatory and Immunomodulatory Potential. AB - Artemisia amygdalina D. is a critically endangered endemic medicinal plant of Kashmir Himalayas. In the current study anti-inflammatory and immunomodulatory activity of the plant was carried out. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC-specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts used as test drugs showed to have anti-inflammatory potential. The methanolic fraction was observed to have the maximum effect on the inhibition of paw edema formation with the inhibitory potential of 42.26%, while in the immunomodulation studies the test drugs were found to have the immunosuppressant activity with methanolic fraction again showing the maximum potential for the suppression of both humoral (55.89% and 47.91%) and cell-mediated immunity (62.27% and 57.21%). The plant in total seems to have the anti-inflammatory potential. The suppression of immune system suggests some mechanistic way by which the inhibition of inflammation takes place. Since, in chronic inflammation like arthritis, there is the involvement of immune system, the plant in that way may serve as an alternative for the treatment of such autoimmune diseases. PMID- 24224115 TI - Antioxidant Activity and Volatile and Phenolic Profiles of Essential Oil and Different Extracts of Wild Mint (Mentha longifolia) from the Pakistani Flora. AB - The antioxidant activity and free radical scavenging capacity of the essential oil and three different extracts of wildly grown Mentha longifolia (M. longifolia) were studied. The essential oil from M. longifolia aerial parts was isolated by hydrodistillation technique using Clevenger-type apparatus. The extracts were prepared with three solvents of different polarity (n-hexane, dichloromethane, and methanol) using Soxhlet extractor. Maximum extract yield was obtained with methanol (12.6 g/100 g) while the minimum with dichloromethane (3.50 g/100 g). The essential oil content was found to be 1.07 g/100 g. A total of 19 constituents were identified in the M. longifolia oil using GC/MS. The main components detected were piperitenone oxide, piperitenone, germacrene D, borneol, and beta -caryophyllene. The total phenolics (TP) and total flavonoids (TF) contents of the methanol extract of M. longifolia were found to be significantly higher than dichloromethane and hexane extracts. The dichloromethane and methanol extracts exhibited excellent antioxidant activity as assessed by 2,2'-diphenyl-1 picrylhydrazyl (DPPH) free radical scavenging ability, bleaching beta -carotene, and inhibition of linoleic acid peroxidation assays. The essential oil and hexane extract showed comparatively weaker antioxidant and free radical scavenging activities. The results of the study have validated the medicinal and antioxidant potential of M. longifolia essential oil and extracts. PMID- 24224116 TI - Utilization of Modern Contraceptives among HIV Positive Reproductive Age Women in Tigray, Ethiopia: A Cross Sectional Study. AB - Background. HIV infected women in sub-Saharan Africa are at substantial risk of unintended pregnancy and sexually transmitted infections. In developing countries including Ethiopia counseling and provision of modern contraceptives of choice to HIV infected women including those on antiretroviral therapy (ART) is an important strategy to prevent unintended pregnancies and sexually transmitted infections. Little is known about the existing practices and utilization of modern contraceptives among HIV positive reproductive age women attending ART units. Objective. The aim of this study was to assess utilization of modern contraceptives and associated factors among HIV positive reproductive age women attending ART units in zonal hospitals of Tigray region, North Ethiopia. Method. Institution based cross-sectional study was conducted by interviewing 364 HIV positive reproductive age women in all zonal hospitals of Tigray region using systematic sampling technique. Structured and pretested questionnaire was used to obtain information from the respondents. Descriptive, bivariate, and multivariate methods were used to analyze utilization of modern contraceptives and the factors associated with it. Result. Three hundred sixty-four subjects participated with a response rate of 99.2%. The mean age of the respondents was 31.9 +/- 6.5 (SD) years. About 46% of participants utilized modern contraceptives, 59.9% out of them used dual method. However, a significant proportion of the respondents (46%) reported that they wished to have a desire for children. Being secondary education and higher (AOR: 2.85; 95% CI: 1.17-6.95) and currently on HAART (AOR: 3.23; 95% CI: 1.49-7.01) they were more likely to utilize modern contraceptive. But those women who were >=25 years old, house wives, single, divorced, or widowed were less likely to utilize modern contraceptive. Conclusion. Results of this study revealed that the number of respondents who were ever heard of modern contraceptives was high. However, modern contraceptive utilization was still low. Additional efforts are needed to promote modern contraceptive utilization in general and dual method use in particular among HIV positive reproductive age women. PMID- 24224117 TI - Apparent Motives for Aggression in the Social Context of the Bar. AB - OBJECTIVE: Little systematic research has focused on motivations for aggression and most of the existing research is qualitative and atheoretical. This study increases existing knowledge by using the theory of coercive actions to quantify the apparent motives of individuals involved in barroom aggression. Objectives were to examine: gender differences in the use of compliance, grievance, social identity, and excitement motives; how motives change during an aggressive encounter; and the relationship of motives to aggression severity. METHOD: We analyzed 844 narrative descriptions of aggressive incidents observed in large late-night drinking venues as part of the Safer Bars evaluation. Trained coders rated each type of motive for the 1,507 bar patrons who engaged in aggressive acts. RESULTS: Women were more likely to be motivated by compliance and grievance, many in relation to unwanted sexual overtures from men; whereas men were more likely to be motivated by social identity concerns and excitement. Aggressive acts that escalated tended to be motivated by identity or grievance, with identity motivation especially associated with more severe aggression. CONCLUSIONS: A key factor in preventing serious aggression is to develop approaches that focus on addressing identity concerns in the escalation of aggression and defusing incidents involving grievance and identity motives before they escalate. In bars, this might include training staff to recognize and defuse identity motives and eliminating grievance-provoking situations such as crowd bottlenecks and poorly managed queues. Preventive interventions generally need to more directly address the role of identity motives, especially among men. PMID- 24224118 TI - Meta-Analysis of Interventions for Reducing Number of Sexual Partners and Drug and Alcohol Abuse among People Living with HIV/AIDS. AB - OBJECTIVE: To perform a systematic review and meta-analysis of the efficacy of risk reduction interventions on HIV-related risk behaviors among people living with HIV/AIDS (PLWHA). METHODS: Studies included in the meta-analysis were randomized clinical trials (RCTs) of risk reduction interventions, which targeted PLWHA aged 18 year or older and assessed the changes of number of sexual partners, drug use, needle sharing, and/or alcohol abuse between pre- and post intervention. The standardized mean differences (SMD) between study arms as well as between baseline and post-intervention, defined as the effect sizes (ES), were calculated in random effects models. Heterogeneity of studies was estimated by the I2 statistic. RESULTS: Twelve RCTs involving 3993 PLWHA were included in our analysis: seven reported impacts on the number of sexual partners, and three reported impacts on drug use, needle sharing, and alcohol abuse, respectively. There were no statistically significant impacts of risk reduction interventions on the number of total sexual partners (mean ES, -0.10; 95% confidence interval [CI], -0.26, 0.06; P=0.22) or on the subset of HIV-negative or unknown-status sexual partners (mean ES, 0.003; 95% CI, -0.54, 0.54; P=0.99). Overall, risk reduction intervention studies documented a reduction of drug abuse (mean ES: 0.26; 95% CI: -0.51, -0.01; P=0.04) among HIV-infected drug users, but this impact was mainly attributable to one study. Risk reduction interventions did not show a reduction of needle sharing (mean ES, -0.15; 95% CI, -0.43, 0.13; P=0.29) or of alcohol abuse (mean ES, -0.10; 95% CI, -0.36, 0.17; P=0.47). No heterogeneity or publication bias was found across individual studies. CONCLUSIONS: Our meta-analysis did not find a positive impacts of risk reduction interventions on number of sexual partners, drug use, needle sharing, or alcohol abuse among PLWHA, but the small number of studies meeting our review criteria limits these findings. PMID- 24224119 TI - Thrombospondin-1 Deficiency Exacerbates the Pathogenesis of Diabetic Retinopathy. AB - Diabetic retinopathy is a leading cause of blindness in the United States. Access to new animal models that exhibit retinal vasculopathies with short duration of diabetes, are vital for understanding the underlying mechanisms and examining the efficacy of new treatment modalities. Our previous studies demonstrated decreased expression of Thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, in eyes from both patients and rodents with diabetes. Here we examined whether TSP1 deficiency could exacerbate diabetic retinal vasculopathies. Akita/+ male mice reproducibly develop diabetes by 4 weeks of age. These mice demonstrated the early non-proliferative stages of diabetic retinopathy, including decreased numbers of pericytes and increased glial cell activation. However, Akita/+ male mice deficient in TSP1 (Akita/+; TSP1-/-) demonstrated more advanced stages of diabetic retinopathy with a 4-fold increase in acellular capillaries and increased fibronectin and GFAP expression. These vascular changes were not attributable to aberrant retinal vascular development in the absence of TSP1, since down-regulation of TSP1 postnatally in the endothelium also resulted in more severe retinopathy. In addition, lack of another endogenous inhibitor of angiogenesis, pigment epithelium derived factor (PEDF), also enhanced diabetic retinopathy in Akita/+ mice. Akita/+; PEDF-/- male mice demonstrated increased numbers of acellular capillaries compared to controls but at a level lower than that observed in Akita/+; TSP1-/- mice. Thus, the exacerbation of diabetic retinopathy in Akita/+; TSP1-/- mice will allow the study of retinal vasculopathies with a shorter duration of diabetes and facilitate future testing of treatment modalities that protect the retinal vasculature and preserve sight. PMID- 24224120 TI - Are Markov and semi-Markov models flexible enough for cognitive panel data? AB - Markov chains and semi-Markov models are standard tools used to describe the flow of subjects from health into various stages of a disease. Applications of these techniques face challenges when modeling the flow of elderly subjects through cognitive states into dementia due to the interval censoring of the entry into cognitive states, the transient nature of pre-dementia cognitive states, time dependent risk factors, missing data, selection bias, and clinical diagnoses that may not agree with the gold standard diagnoses obtained at autopsy. There is a need to make these tools more flexible if they are to be used effectively when analyzing cognitive panel data. PMID- 24224121 TI - Synergistic Effect of AJW200, a von Willebrand Factor Neutralizing Antibody with Low Dose (0.9 mg/mg) Thrombolytic Therapy Following Embolic Stroke in Rabbits. AB - The von Willebrand factor (vWF) is an acute stroke response protein involved in platelet aggregation, adhesion, inflammation, and thrombus formation, responses that occur following an ischemic stroke. We hypothesize that administration of an anti-vWF antibody (anti-vWF-Ab) may be used as adjunctive therapy with tissue plasminogen activator (tPA) to promote behavioral improvement following an embolic stroke. In this proof-of-concept study, which used a blinded and randomized design, we studied delayed treatment with the anti-vWF-Ab, AJW200 (0.30 mg/kg), alone or in combination with a rabbit low-dose of tPA (0.9 mg/kg) using the rabbit small clot embolic stroke model (RSCEM) with behavioral function as the primary clinically relevant endpoint. To evaluate the quantitative relationship between clot burden in brain and clinical scores, so that an effective stroke dose (P50) could be calculated, logistic sigmoidal quantal analysis curves were constructed. A beneficial treatment significantly increases P50 compared to control. The effect of antibody administration, either alone or with low dose tPA was compared to a "positive control", a standard rabbit optimized dose of tPA (3.3 mg/kg), as a measure of the maximum improvement potential in the RSCEM. The anti-vWF-Ab, AJW200, or control IgG were administered IV 1 hour following embolization, and behavior was measured 48 hours later. AJW200 plus low-dose tPA significantly increased the P50 value by 74% (p<0.05, t=2.612) and 81% (p<0.05, t=2.519) compared to low dose tPA or IgG, respectively, but not the AJW200 group (p>0.05). AJW200 increased the P50 value by 28%, (p>0.05) compared to the control IgG-treated group. Standard dose tPA increased the P50 value by 154% (p<0.05). Statistically, the combination response for AJW200 plus low-dose tPA was not significantly different from standard dose tPA (p=0.26). This study shows that the concomitant administration of the anti-vWF-Ab AJW200 with low dose tPA is synergistic and results in significantly improved behavioral function following embolic stroke. We postulate that neutralization of vWF may suppress or attenuate one or more aspects of the acute phase stroke cascade response including suppression of inflammatory response and reduced leukocyte adhesion. PMID- 24224122 TI - NFkappaB function and regulation in cutaneous T-cell lymphoma. AB - The nuclear accumulation and transcriptional activity of NFkappaB are constitutively increased in cutaneous T-cell lymphoma (CTCL) cells, and are responsible for their increased survival and proliferation. However, in addition to the anti-apoptotic and pro-inflammatory genes, NFkappaB induces expression of immunosuppressive genes, such as IL-10 and TGFbeta, which inhibit the immune responses and are characteristic for the advanced stages of CTCL. While the mechanisms regulating NFkappaB-dependent transcription of anti-apoptotic and pro inflammatory genes have been studied extensively, very little is known about the NFkappaB regulation of immunosuppressive genes. The specificity of NFkappaB regulated responses is determined by the subunit composition of NFkappaB complexes recruited to the individual promoters, post-translational modifications of NFkappaB proteins, as well as by their interactions with other transcriptional factors and regulators. In this review, we discuss the mechanisms regulating the transcription of NFkappaB-dependent anti-apoptotic, pro-inflammatory and immunosuppressive genes in CTCL cells, as potential targets for CTCL therapies. PMID- 24224123 TI - Clinical implications for loss or diminution of expression of Raf-1 kinase inhibitory protein and its phosphorylated form in ductal breast cancer. AB - Raf Kinase inhibitory protein (RKIP) is a well-established metastasis suppressor that is frequently downregulated in aggressive cancers. The impact of RKIP and its phosphorylated form on disease-free survival (DFS) and other clinicopathological parameters in breast cancer is yet to be discovered. To this end, we examined RKIP expression in 3 independent breast cancer cohorts. At the Protein level, loss or reduced total RKIP expression was associated with large sized tumors characterized by high proliferative index, high-grade and diminished estrogen (ER) and progesterone receptor expression. Loss or diminution of RKIP expression was significantly associated with shorter DFS in all cohorts. Moreover, the complete loss of p-RKIP was an independent prognostic factor using multivariate analysis in operable invasive ductal breast cancer. We show for the first time that ER, partly, drives RKIP expression through MTA3-Snail axis. Consistent with this finding, we found that, at the mRNA level, RKIP expression varied significantly across the different molecular subtypes of breast cancer with the Luminal (ER+) subtype expressing high levels of RKIP and the more aggressive Claudin-low (ER-) subtype, which depicted the highest epithelial to mesenchymal transition (EMT) registered the lowest RKIP expression levels. In conclusion, loss of expression/diminution of RKIP or its phosphorylated form is associated with poor diseases-free survival in breast cancer. Determining the expression of RKIP and p-RKIP adds significant prognostic value to the management and subtyping of this disease. PMID- 24224124 TI - Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA. AB - Pancreatic cancer is the fourth leading cause of cancer related death in the US and exhibits aggressive features with short survival rate and high mortality. Therefore, it is important to understand the molecular mechanism(s) involved in the aggressive growth of pancreatic cancers, and further design novel targeted therapies for its treatment with better treatment outcome. In the present study, we found that the expression of miR-221 was significantly up-regulated in pancreatic cancer cell lines and tumor tissues compared to normal pancreatic duct epithelial cells and normal pancreas tissues. Moreover, we found that the pancreatic cancer patients with high miR-221 expression had a relatively shorter survival compared to those with lower expression, suggesting that miR-221 could be an oncogenic miRNA and a prognostic factor for poor survival of patients. Interestingly, transfection of miR-221 inhibitor suppressed the proliferative capacity of pancreatic cancer cells with concomitant up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA, which are the tumor suppressors and the predicted targets of miR-221. Most importantly, we found that the treatment of pancreatic cancer cells with isoflavone mixture (G2535), formulated 3,3'-diindolylmethane (BR-DIM), or synthetic curcumin analogue (CDF) could down-regulate the expression of miR-221 and consequently up-regulate the expression of PTEN, p27(kip1), p57(kip2), and PUMA, leading to the inhibition of cell proliferation and migration of MiaPaCa-2 and Panc-1 cells. These results provide experimental evidence in support of the oncogenic role of miR-221 and also demonstrate the role of isoflavone, BR-DIM, and CDF as potential non-toxic agents that are capable of down-regulation of miR-221. Therefore, these agents combined with conventional chemotherapeutics could be useful in designing novel targeted therapeutic strategy for the treatment of pancreatic cancer for which there is no curative therapy. PMID- 24224125 TI - Functional analysis of Drosophila DNA polymerase epsilon p58 subunit. AB - DNA polymerase epsilon (polepsilon) plays a central role in DNA replication in eukaryotic cells, and has been suggested to the main synthetic polymerase on the leading strand. It is a hetero-tetrameric enzyme, comprising a large catalytic subunit (the A subunit ~250 kDa), a B subunit of ~60 kDa in most species (~80 kDa in budding yeast) and two smaller subunits (each ~20 kDa). In Drosophila, two subunits of polepsilon (dpolepsilon) have been identified. One is the 255 kDa catalytic subunit (dpolepsilonp255), and the other is the 58 kDa subunit (dpolepsilonp58). The functions of the B subunit have been mainly studied in budding yeast and mammalian cell culture, few studies have been performed in the context of an intact multicellular organism and therefore its functions in this context remain poorly understood. To address this we examined the in vivo role of dpolepsilonp58 in Drosophila. A homozygous dpolepsilonp58 mutant is pupal lethal, and the imaginal discs are less developed in the third instar larvae. In the eye discs of this mutant S phases, as measured by BrdU incorporation assays, were significantly reduced. In addition staining with an anti-phospho histone H3 (PH3) antibody, (a marker of M phase), was increased in the posterior region of eye discs, where usually cells stop replicating and start differentiation. These results indicate that dpolepsilonp58 is essential for Drosophila development and plays an important role in progression of S phase in mitotic cell cycles. We also observed that the size of nuclei in salivary gland cells were decreased in dpolepsilonp58 mutant, indicating that dpolepsilonp58 also plays a role in endoreplication. Furthermore we detect a putative functional interaction between dpolepsilon and ORC2 in discs suggesting that polepsilon plays a role in the initiation of DNA replication in Drosophila. PMID- 24224126 TI - Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer. AB - Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific beta1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch's response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation. PMID- 24224127 TI - Enhancement of taxol, doxorubicin and zoledronate anti-proliferation action on triple-negative breast cancer cells by a PTHrP blocking monoclonal antibody. AB - Triple-negative breast cancers (TNBCs) are heterogeneous cancers that present tumors without the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Because of the absence of these receptors, there are currently no known specific molecular targets for treatment, and although TNBC tumors are chemosensitive, prognosis is poor because this type of cancer relapses more frequently and more aggressively than hormone receptor positive cancers. The mechanisms by which TNBCs escape control by chemotherapy are not clear, and it is crucial to identify novel molecular drivers that can be targeted in order to develop more efficient therapeutic approaches. We recently highlighted a pleiotropic role for parathyroid hormone-related protein (PTHrP) in all stages of breast cancer, and used our neutralizing anti-PTHrP monoclonal antibody (mAb M158) to efficiently inhibit progression and metastasis of human breast cancer xenografts in athymic mice. In the present study, we present evidence for a strong in vitro anti-proliferative effect of our blocking anti PTHrP mAb M158 as a single agent on TNBC lines of various subtypes that are known to express PTHrP (MDA-MB-231, BT-549, MDA-MB-435). The same mAb is inactive in a TNBC line without detectable PTHrP expression (MDA-MB-468). In in vitro combination studies, the mAb enhances the effect of the chemotherapeutic drugs taxol and doxorubicin in PTHrP-positive TNBC cells in an additive manner. When combined with the bisphosphonate zoledronate, M158 can act in additive or antagonistic fashion in vitro depending on the cell line. Our observations identify PTHrP as a novel target against TNBC cell proliferation, and suggest that combination therapies that include an anti-PTHrP approach might increase treatment efficacy in patients with PTHrP-positive TNBC. PMID- 24224128 TI - Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma. AB - Gene amplified in squamous cell carcinoma 1 (GASC1) is a member of Jumonji C domain containing histone demethylases that play an essential role in affecting chromatin architecture and gene expression. The purpose of this study was to determine the expression features and the clinical significance of GASC1 in esophageal squamous cell carcinoma (ESCC). GASC1 expression was detected on tissue microarrays of ESCC samples in 185 cases using immunohistochemical staining. Strong nuclear staining for GASC1 was observed in a subset of ESCC samples. The nuclear expression of GASC1 was significantly associated with lymph node metastasis (P=0.030) and tumor-node metastasis stages (P=0.013). Kaplan Meier survival analysis showed a tendency that high expression of GASC1 in the nucleus was associated with poor survival of ESCC patients, with a 5-year survival rate of 26.5%, as compared to 43.7% for patients with GASC1-negative/low expression. Furthermore, multivariate analysis revealed that high expression of GASC1 likely acts as a predictive factor for overall survival of ESCC patients, despite the P-value failing to reach significance (P=0.059). The findings indicate that histone demethylase GASC1 may play an important role in promoting cancer metastasis, and shed new light on the importance of targeting GASC1 to suppress metastatic disease in various tumor types, including ESCC. PMID- 24224129 TI - The Social Security Death Index (SSDI) most accurately reflects true survival for older oncology patients. AB - INTRODUCTION: The ability to ascertain survival information is important for retrospective and prospective studies. Two databases that can be used are the Social Security Death Index (SSDI) and the National Death Index (NDI). Although the NDI is more complete, there are advantages to the SSDI such as ease of use and cost. The intent of this study was to determine accuracy of the SSDI. METHODS: Publically available data on all known deceased individuals in the state of Ohio in 2003 were obtained from the State of Ohio Department of Health. A random sample of 63,557 of these were compared to the SSDI to identify risk factor for inclusion/exclusion. RESULTS: Overall, 94.7% of all death records were confirmed by the SSDI. Age at death, gender, race, ethnicity, and cause of death were all found to significantly affect the likelihood of inclusion. Specifically, people aged 18-24 were included only 79.8% of the time compared to 96.2% for those over the age of 65. Also, malignancy as cause of death resulted in a 95.3% inclusion while trauma as a cause of death led to 86.5% inclusion. While Caucasians had an inclusion of 95.6%, African Americans were included only 87.8% of the time. Hispanics and women also had lower inclusion rates. DISCUSSION: The SSDI is a strong tool for following up on participants lost to follow up in certain populations but is weaker in others. The SSDI would be particularly useful in a population that is largely older, Caucasian, or has malignant disease. PMID- 24224130 TI - Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy. AB - BACKGROUND: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. METHODS: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status. RESULTS: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort. CONCLUSION: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment. PMID- 24224131 TI - "White Box" Epidemiology and the Social Neuroscience of Health Behaviors: The Environmental Affordances Model. AB - Crucial advances have been made in our knowledge of the social determinants of health and health behaviors. Existing research on health disparities, however, generally fails to address a known paradox in the literature: While blacks have higher risk of medical morbidity relative to non-Hispanic whites, blacks have lower rates of common stress-related forms of psychopathology such as major depression and anxiety disorders. In this article we propose a new theoretical approach, the Environmental Affordances Model, as an integrative framework for the origins of both physical and mental health disparities. We highlight early empirical support and a growing body of experimental animal and human research on self-regulatory health behaviors and stress coping that is consistent with the proposed framework. We conclude that transdisciplinary approaches, such as the Environmental Affordances Model, are needed to understand the origins of group based disparities to implement effective solutions to racial and ethnic group inequalities in physical and mental health. PMID- 24224132 TI - Mechanisms of load dependency of myocardial ischemia reperfusion injury. AB - Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further, systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately exacerbate ischemia reperfusion injury. PMID- 24224134 TI - Gambogic acid suppresses pressure overload cardiac hypertrophy in rats. AB - Cardiac hypertrophy is a common response of the heart to a variety of cardiovascular stimuli. Pathological cardiac hypertrophy eventually leads to heart failure. Gambogic acid (GA) is a main active ingredient isolated from the gamboge resin of Garcinia hanburyi trees and has potent anti-tumor and anti inflammatory effects that are associated with inhibition of the NF-kappaB pathway. We and others recently reported that GA can significantly inhibit the function of the proteasome with much less toxicity than conventional proteasome inhibitors. The increasing lines of evidence indicate that the inhibition of the proteasome can promote the regression of cardiac hypertrophy induced by pressure overload through the blockade of the NF-kappaB pathway. In the present study, we examined the effect of GA on pressure overload or isoproterenol infusion induced cardiac hypertrophy and fibrosis, and changes in myocardial NF-kappaB signaling. We observed that the heart weight/body weight ratio, the size of cardiomyocytes, interstitial fibrosis, and the reactivation of fetal genes (alpha-SK-actin and BNP mRNA) were markedly increased by abdominal aorta constriction (AAC) or isoproterenol infusion (ISO), all of which were effectively inhibited by GA treatment. Furthermore, GA treatment abolished proteasome chymotrypsin-like activity increases induced by AAC or ISO, led to increased myocardial IkappaB protein, decreased NF-kappaB p65 subunit levels in the nuclear fraction, decreased NF-kappaB DNA-binding activity, and reduced IL2 levels in the myocardium of rats subject to AAC or ISO. In conclusion, GA treatment can suppress cardiac hypertrophy and fibrosis induced by pressure overload or isoproterenol possibly through the inhibition of the proteasome and the NF-kappaB pathway, suggesting that GA treatment may provide a new strategy to treat cardiac hypertrophy. PMID- 24224135 TI - Heart rate variability and metabolic rate in healthy young adults with low birth weight. AB - OBJECTIVE: Low birth weight (LBW) is associated with obesity and a higher cardiovascular risk in adult life. Since autonomic dysfunction could be a pathophysiological factor for this association, we assessed the impact of LBW on cardiac autonomic activity and metabolic rate in young adulthood. We hypothesized that the autonomic tone could be coupled with the metabolic rate in subjects with LBW. METHODS: Heart rate variability (HRV) from 24-hour Holter-electrocardiograms was measured in 15 healthy adults aged 20 to 30 years with LBW (<2500g at term) and 15 paired subjects with normal birth weight (NBW). The pairs were closely matched by gender, age, and body mass index. Resting energy expenditure was measured by indirect calorimetry and body composition by bioimpedance. RESULTS: Global HRV parameters were significantly higher in the LBW group and a marked difference was observed in the long wave fluctuations of the frequency domain (very low frequency). These fluctuations were positively correlated with the resting energy expenditure per body weight in the LBW and negatively in the NBW group. Only in the LBW group HRV was closely related to body fat. INTERPRETATION: This case-control study indicates that autonomous nervous function is not generally deteriorated in young adults with LBW and has a significant association with metabolic rate. Thus, it may be a determinant of the body weight regulation in this group. The higher cardiovascular risk in ageing individuals with LBW would therefore rather be a consequence of weight gain than of a primary autonomous nervous dysfunction. PMID- 24224136 TI - Publication trends in noninvasive cardiovascular imaging: 1991-2011: a retrospective observational study. AB - The last twenty years have seen an explosive growth in cardiovascular disease research. The purpose of our study was to evaluate the characteristics of published research in the field of non-invasive cardiovascular imaging research from 1991-2011. Our aims were to determine: (1) the origin of the studies (international or from the U.S.) (2) differences in funding sources for U.S. publications and (3) if there has been an evolving trend pertaining to the mode of imaging. We evaluated characteristics of original research articles from Circulation, Circulation cardiovascular imaging, Journal of the American College of Cardiology (JACC), Journal of the American College of Cardiology cardiovascular imaging, Journal of the American Medical Association and the New England Journal of Medicine for the years 1991-91, 2001-02 and 2010-11. To establish trends for contributions for U.S. based studies and proportions of U.S. based studies receiving NIH funding in the study period, data was compared using a chi-square test. A two sided p value of less than or equal to 0.05 was used as the threshold for significance. Differences in modes of imaging under study were made by comparing average number of publications between the data sets in the study period using a t-test analysis. A total of 5431 studies were reviewed; 594 studies were selected as per the standardized abstraction criteria. U.S. based publications outnumbered international publications; its' share declined from 77% in 1991-92 to 57% in 2010-2011 (p<0.0001). Funding for U.S. publications by the National Institutes of Health (NIH) remained static (1991-92: 40%; 2001-02: 49%; 2010-11: 42%). A decline was seen in the investigation of echocardiography (47%, p=0.44); cardiac computed tomography and cardiac magnetic resonance imaging studies grew 6.5 times (p=0.002) and 7-fold (p=0.01) respectively. Nuclear cardiology imaging fell by more than 50% (p=0.02). The last twenty years have seen a globalization of research in non-invasive cardiovascular imaging with a shift in focus towards investigation of cardiac magnetic resonance imaging. The decline in U.S. based publications coupled with a stasis in NIH funding may call for increased federal support for non-invasive imaging research. PMID- 24224137 TI - A predictor of atheroma progression in patients achieving very low levels of low density lipoprotein cholesterol. AB - An aggressive reduction in low-density lipoprotein cholesterol (LDL-C) with statins produces regression or stabilization of coronary artery plaques. However, after achieving very low levels of LDL-C, atheroma regression is not observed in all patients. The purpose of the present study was to evaluate the determinants of atheroma progression despite achieving very low levels of LDL-C. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound in the TRUTH study. Of these, 33 patients who achieved an on-treatment LDL-C level of <70 mg/dl were divided into 2 groups according to increase in plaque volume (progressors, n= 16) or decrease in plaque volume (regressors, n= 17) during an 8-month follow-up period. At the 8 month follow-up, serum LDL-C and apolipoprotein B levels were significantly lower in progressors than in regressors; however, significant increases in high-density lipoprotein cholesterol and apolipoprotein AI and decreases in high-sensitivity C reactive protein and oxidized LDL were observed only in regressors. The changes in the n-3 to n-6 polyunsaturated fatty acid ratios significantly differed between the 2 groups. Multivariate regression analysis showed that a decrease in the eicosapentaenoic acid + docosahexaenoic acid/arachidonic acid ratio was a significant predictor associated with atheroma progression (beta= -0.512, p= 0.004). In conclusions, n-3 to n-6 polyunsaturated fatty acid ratios affected coronary artery plaque progression and regression in patients who achieved very low levels of LDL-C during statin therapy. PMID- 24224133 TI - Evidence of endothelial dysfunction in the development of Alzheimer's disease: Is Alzheimer's a vascular disorder? AB - The etiology of Alzheimer's disease (AD) remains unclear. The emerging view is that cerebrovascular dysfunction is a feature not only of cerebrovascular diseases, such as stroke, but also of neurodegenerative conditions, such as AD. In AD, there is impaired structure and function of cerebral blood vessels and cells in the neurovascular unit. These effects are mediated by vascular oxidative stress. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood-brain barrier and reduces the brain's repair capacity. Such injury can exacerbate the cognitive dysfunction exerted by incident ischemia and coexisting neurodegeneration. This article summarises data regarding cardiovascular risk factors, vascular abnormalities and brain endothelial damage in AD. In view of accumulating evidence of vascular pathology in AD, we also review the literature (MEDLINE, EMBASE) for clinical evidence of impaired endothelial function in AD. A total of 15 articles investigating endothelial dysfunction in AD were identified. 10 of these articles showed impaired endothelial function in AD patients. The current literature suggests endothelial dysfunction may be involved in the pathogenesis of AD. This aspect of AD pathology is particularly interesting in view of its potential for therapeutic intervention. Future research on endothelial function in AD should concentrate on population-based analysis and combine multiple methods to evaluate endothelial function. PMID- 24224138 TI - How can we identify the optimal pacing site in the right ventricular septum? A simplified method applicable during the standard implanting procedure. AB - AIMS: A short paced (p) QRS duration (d) can be a marker for selecting the most appropriate RV pacing site. Although this could be achieved by continual 12-Lead ECG monitoring, such a technique is not applicable during pacemaker (PM) implantation. The purpose of this study was to validate a method for identifying the optimal site for RV septum pacing using simple markers derived from few real time ECG leads and fluoroscopy (F). METHODS AND RESULTS: An overall of 304 measurements of pQRSd in different RV sites was performed in 102 patients undergoing PM implant. In accordance with F position the lead placement was classified high, medium, and low septum. Paced electrocardiographic/fluoroscopic parameters (q-wave/negative QRS in lead I, notching in limb leads, R/S wave in lead II, QRS precordial leads transition, and F septal segments pacing site) were analyzed to predict short pQRSd (<= 160 ms). Logistic regression analysis showed that pQRSd > 160 ms was predicted by presence of pQRS notching in limb leads (OR = 3.24, p < 0.001), and with negative amplitude of QRS in lead II (OR = 2.53, p = 0.03). Short pQRSd (<= 160 ms) was observed with mid F position (OR = 0.31, p < 0.001) and with the presence of a q-wave/negative QRS in lead I. CONCLUSION: In RV septum pacing, simple QRS markers of few limb leads (lead I/II) added to F position are usefull to identifying the optimal site to place the RV lead. PMID- 24224139 TI - A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study. AB - OBJECTIVE: Psoriasis (PSO) and rheumatoid arthritis (RA) increase cardiovascular diseases (CVD) beyond traditional risk factors. Vascular inflammation has previously been demonstrated to be present in PSO and RA using [18F] fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. However, vascular inflammation has not been compared in these two disorders relative to a healthy reference population. Thus, vascular inflammation was quantitatively assessed in patients with PSO (n=10), RA (n=5), and healthy subjects (n=10) using FDG-PET/CT. METHODS: FDG-PET/CT mean standardized uptake value (SUVmean) was determined slice by slice within the ascending, aortic arch, descending thoracic, suprarenal abdominal, and infrarenal abdominal aorta, and the mean metabolic volumetric product (MVPmean) was then calculated for each aortic subsegment. Plasma lipids and metabolic and inflammatory markers were also assessed. RESULTS: CVD risk profiles were largely similar across groups. After adjustment for CV risk factors, regional aortic vascular inflammation based on MVPmean was elevated for both PSO (beta coefficients 0.31-1.47, p<0.001) and RA (beta coefficients 0.15-0.69, p<0.05) compared to healthy subjects. CONCLUSIONS: These observations using FDG-PET/CT to estimate vascular inflammation support epidemiological findings of premature atherosclerosis in PSO and RA. The use of FDG-PET/CT to investigate vascular inflammation across systemic inflammatory diseases warrants further examination in larger study populations. PMID- 24224140 TI - Combinations of acute coronary syndromes and Takotsubo syndrome. PMID- 24224141 TI - Thrombus aspiration might reduce the need for concomitant stenting in young patients with STEMI. PMID- 24224142 TI - Toward plasmonics-enabled spatiotemporal activity patterns in three-dimensional culture models. AB - Spatiotemporal activity patterns of proteases such as matrix metalloproteinases and cysteine proteases in organs have the potential to provide insight into how organized structural patterns arise during tissue morphogenesis and may suggest therapeutic strategies to repair diseased tissues. Toward imaging spatiotemporal activity patterns, recently increased emphasis has been placed on imaging activity patterns in three-dimensional culture models that resemble tissues in vivo. Here, we briefly review key methods, based on fluorogenic modifications either to the extracellular matrix or to the protease-of-interest, that have allowed for qualitative imaging of activity patterns in three-dimensional culture models. We highlight emerging plasmonic methods that address significant improvements in spatial and temporal resolution and have the potential to enable quantitative measurement of spatiotemporal activity patterns with single-molecule sensitivity. PMID- 24224144 TI - 27-day cycles in human mortality: Traute and Bernhard Dull. AB - This tribute to her parents by one co-author (NDP) is the fruit of a more than a decade-long search by the senior author (FH) for the details of the lives of Bernhard and Gertraud ("Traute") Dull. These pioneers studied how space/terrestrial weather may differentially influence human mortality from various causes, the 27-day mortality pattern being different whether death was from cardiac or respiratory disease, or from suicide. FH is the translator of personal information about her parents provided by NDP in German. Figuratively, he also attempts to "translate" the Dulls' contribution in the context of the literature that had appeared before their work and after their deaths. Although the Dulls published in a then leading journal, among others (and FH had re analyzed some of their work in a medical journal), they were unknown to academies or libraries (where FH had inquired about them). The Dulls thoroughly assembled death certificates to offer the most powerful evidence for an effect of solar activity reflected in human mortality, as did others before them. They went several steps further than their predecessors, however. They were the first to show possibly differential effects of space and/or Earth weather with respect to suicide and other deaths associated with the nervous and sensory systems vs. death from cardiac or respiratory disease as well as overall death by differences in the phase of a common 27-day cycle characterizing these mortality patterns. Furthermore, Bernhard Dull developed tests of human visual and auditory reaction time to study effects of weather and solar activity, publishing a book (his professorial dissertation) on the topic. His unpublished finding of an increased incidence of airplane crashes in association with higher solar activity was validated after his death, among others, by Tatiana Zenchenko and A. M. Merzlyi. PMID- 24224143 TI - Intravitreal Corticosteroids in the Management of Diabetic Macular Edema. AB - Diabetic macular edema (DME) remains an important worldwide cause of visual loss. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants. At this time, no steroid is approved by the United States Food and Drug Administration (FDA) for the treatment of DME. PMID- 24224145 TI - DNA ligases as therapeutic targets. AB - During DNA replication, DNA joining events link Okazaki fragments on the lagging strand. In addition, they are required to repair DNA single- and double-strand breaks and to complete repair events initiated by the excision of mismatched and damaged bases. In human cells, there are three genes encoding DNA ligases. These enzymes are ATP-dependent and contain a conserved catalytic region. Biophysical studies have shown that the catalytic region contains three domains that, in the absence of DNA, are in an extended conformation. When the catalytic region engages a DNA nick, it adopts a compact, ring structure around the DNA nick with each of the three domains contacting the DNA. Protein-protein interactions involving the regions flanking the conserved catalytic regions of human DNA ligases play a major role in directing these enzymes to participate in specific DNA transactions. Among the human LIG genes, the LIG3 gene is unique in that it encodes multiple DNA ligase polypeptides with different N- and C-termini. One of these polypeptides is targeted to mitochondria where it plays an essential role in the maintenance of the mitochondrial genome. In the nucleus, DNA ligases I, III and IV have distinct but overlapping functions in DNA replication and repair. Small molecule inhibitors of human DNA ligases have been identified using structure-based approaches. As expected, these inhibitors are cytotoxic and also potentiate the cytotoxicity of DNA damaging agents. The results of preclinical studies with human cancer cell lines and mouse models of human cancer suggest that DNA ligase inhibitors may have utility as anti-cancer agents. PMID- 24224146 TI - Reappraisal of Regional Growth Charts in the Era of WHO Growth Standards. AB - After the WHO Growth Standards (WHOGS) was published in 2006, many countries in the world endorsed and adopted the new growth references as a standard measure for the growth of infants and young children. Certainly, the WHOGS has an impact on the global policy about obesity and underweight in children. Such WHOGS innovation has influenced many regional health authorities and academies, which have managed their own growth charts for a long time, in changing their strategies to develop and use regional growth charts. In Korea, along with the tradition to create a national growth chart every decade, we now face a new era of advancing with the WHOGS. PMID- 24224147 TI - Obesity, inflammation and diet. AB - Obesity is a state in which there is an over-accumulation of subcutaneous and/or abdominal adipose tissue. This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue produces and releases a variety of adipokines (leptin, adiponectin, resistin, and visfatin), as well as pro- and anti inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-4, IL-6, and others). Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes mellitus or cardiovascular disease. Obesity is thus an underlying condition for inflammatory and metabolic diseases. Diet or dietary patterns play critical roles in obesity and other pathophysiological conditions. A healthy diet and some nutrients are generally considered beneficial; however, some dietary nutrients are still considered controversial. In this article, dietary factors that influence inflammation associated with obesity are discussed. PMID- 24224148 TI - Polyunsaturated Fatty acids in children. AB - Polyunsaturated fatty acids (PUFAs) are the major components of brain and retina, and are the essential fatty acids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fatty acids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fatty acids could bring about the shortage of essential fatty acids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs. PMID- 24224149 TI - Clinical features and role of viral isolates from stool samples of intussuception in children. AB - PURPOSE: To detect major acute gastroenteritis virus (rotavirus, norovirus, astrovirus, and enteric adenovirus) and non-enteric type of adenovirus (AdV) in the stools of intussusception patients and to investigate the clinical role of detected viruses. METHODS: From March 2012 to February 2013, major acute gastroenteritis virus and non-enteric type of AdV were isolated from stool samples that collected from 44 patients treated for intussusception in Chungnam National University Hospital. Patients were divided according to age and isolated virus. RESULTS: Virus was detected in 28 (63%) stool specimens. The virus detection rate was significantly lower in patients aged under 12 months (p = 0.04). Twenty-two patients (78.6%) had non-enteric adenovirus, 4 (14.3%) had norovirus, 1 (3.6%) had sapovirus, and 1 (3.6%) had astrovirus. AdV subgroup C (AdV 1, 2, 5, and 6) comprised the majority with 20 cases (90.9%). A monthly increment-and-decrement pattern of intussusception was similar to that of viral detection in the stool samples. Enema reductions were successful in 39 patients and surgical manual reductions were performed in 5 patients. Virus was detected in 24 patients (61.5%) of enema reduction group and 4 patients (80.0%) of surgical manual reduction group. All of the detected viruses were non-enteric adenovirus subgroup C (AdV 1, 5, and 6) in surgical reduction patients. CONCLUSIONS: The virus detection rate was high in the stools of intussusception patients. The pattern of seasonal intussusception occurrence rate was parallel with seasonal these viral detection rate in the stool samples. These findings suggest that viral infection plays an important role in the development of intussusception and further research is warranted. PMID- 24224150 TI - Adverse events associated with azathioprine treatment in korean pediatric inflammatory bowel disease patients. AB - PURPOSE: This study was aimed to evaluate the frequency and course of adverse events associated with azathioprine treatment in Korean pediatric patients with inflammatory bowel disease. METHODS: Total of 174 pediatric patients (age range, 1 to 19 years) with inflammatory bowel disease who received azathioprine in order to maintain remission at Samsung Medical Center (Seoul, Korea) from January 2002 through December 2012 were included in this study. Medical records of these subjects were retrospectively reviewed regarding the development of adverse events associated with azathioprine treatment. RESULTS: Ninety-eight patients (56.3%) of 174 patients experienced 136 episodes of adverse events, requiring dose reduction in 31 patients (17.8%), and discontinuation in 18 patients (10.3%). The mean dose of azathioprine that had been initially administered was 1.32+/-0.42 mg/kg/day. Among the adverse reactions, bone marrow suppression developed in 47 patients (27.0%), requiring dose reduction in 22 patients (12.6%) and discontinuation in 8 patients (4.6%). Other adverse events that occurred were gastrointestinal disturbance (15.5%), hair loss (12.1%), pancreatitis (7.5%), arthralgia (6.9%), hepatotoxicity (2.9%), skin rash/allergic reactions (2.9%), headache/dizziness (2.3%), sepsis (0.6%), and oral mucositis (0.6%). CONCLUSION: Bone marrow suppression, especially leukopenia was most commonly associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Close observation for possible adverse events is required in this population with inflammatory bowel diseases who are under treatment with azathioprine. PMID- 24224151 TI - Pre-diagnostic Clinical Presentations and Medical History Prior to the Diagnosis of Inflammatory Bowel Disease in Children. AB - PURPOSE: The clinical presentations of inflammatory bowel disease (IBD) prior to diagnosis are so diverse or vague that many of them waste time before final diagnosis. This study was undertaken to know the medical history of the pediatric patients until the final diagnosis could be reached. METHODS: The medical records of all pediatric patients who were diagnosed with IBD (Crohn's disease [CD] in 14 children, ulcerative colitis [UC] in 17) during the last 13 years were reviewed. We investigated the length of the diagnostic time lag, chief clinical presentation, and any useful laboratory predictor among the routinely performed examinations. Indeterminate colitis was not included. RESULTS: The mean ages of children at the final diagnosis was similar in both diseases. As for the pre clinical past history of bowel symptoms in CD patients, 5 were previously healthy, 9 had had 1-3 gastrointestinal (GI) symptoms, weight loss, bloody stool, anemia and rectal prolapse. With UC, 9 were previously healthy, 8 had had 1-3 GI symptoms, bloody stool, anorexia. The average diagnostic time lag with CD was 3.36 months, and with UC 2.2 months. Body mass index (BMI) and the initial basic laboratory data (white blood cell, hemoglobin, mean corpuscular volume, serum albumin, and serum total protein) were lower in CD, statistically significant only in BMI. CONCLUSION: IBD shows diverse clinical symptoms before its classical features, making the patients waste time until diagnosis. It is important to concern possibility of IBD even in the mildly sick children who do not show the characteristic symptoms of IBD. PMID- 24224152 TI - A case of esophageal candidiasis in an adolescent who had frequently received budesonide nebulizing therapy. AB - Corticosteroid (budesonide) nebulizer therapy is commonly performed. Its side effects have been considered as being safe or ignorable. The authors present a case of esophageal candidiasis in a healthy female adolescent who was treated with budesonide nebulizer therapy a few times for a cough during the previous winter season. This child presented with dysphagia and epigastric pain for 1 month. Esophageal endoscopy showed a whitish creamy pseudomembrane and erosions on the esophageal mucosa. Pathologic findings showed numerous candidal hyphae. She did not show any evidence of immunodeficiency, clinically and historically. The esophageal lesion did not resolve naturally. The esophageal lesion completely improved with the antifungal therapy for 2 weeks; the symptoms disappeared, and the patient returned to normal health. It is important that frequent esophageal exposure to topical corticosteroids application can cause unexpected side effects. PMID- 24224153 TI - Congenital internal hernia presented with life threatening extensive small bowel strangulation. AB - Internal hernia (IH) is a rare cause of small bowel obstruction occurs when there is protrusion of an internal organ into a retroperitoneal fossa or a foramen in the abdominal cavity. IH can be presented with acute or chronic abdominal symptom and discovered by accident in operation field. However, various kinds of imaging modalities often do not provide the assistance to diagnose IH preoperatively, but computed tomography (CT) scan has a high diagnostic accuracy. We report a case of congenital IH in a 6-year-old boy who experienced life threatening shock. CT scan showed large amount of ascites, bowel wall thickening with poor or absent enhancement of the strangulated bowel segment. Surgical exploration was performed immediately and had to undergo over two meters excision of strangulated small bowel. To prevent the delay in the diagnosis of IH, we should early use of the CT scan and take urgent operation. PMID- 24224154 TI - Congenital chloride diarrhea in dizygotic twins. AB - Congenital chloride diarrhea (CLD) is a rare inherited autosomal recessive disorder. Mutations of the solute carrier family 26 member 3 gene cause profuse, chloride ion rich diarrhea, which results in hypochloremia, hyponatremia and metabolic alkalosis with dehydration. If a fetal ultrasound shows bowel dilatation suggestive of bowel obstruction, or if a neonate shows persistent diarrhea and metabolic alkalosis, CLD should be considered in the differential diagnosis. The severity of CLD varies, but early detection and early therapy can prevent complications including growth failure. We report a case of dizygotic twins affected by CLD who had been born to non-consanguineous parents. Both of them showed growth failure, but one of the twins experienced worse clinical course. He showed developmental delay, along with dehydration and severe electrolyte imbalance. He was diagnosed with CLD first at 6-month age, and then the other one was also diagnosed with CLD. PMID- 24224155 TI - Acute Urinary Retention in a 47-month-old Girl Caused by the Giant Fecaloma. AB - We present a case of a 47-month-old female suffering from acute urinary bladder neck obstruction and bilateral hydronephrosis secondary to a fecaloma. Fecaloma is defined as an accumulation of inspissated feces in the colon or rectum giving the appearance of an abdominal mass. A fecaloma can be developed by diverse causes and the causes of the fecaloma in this case were septum reformation after the Duhamel procedure and long-term constipation. Chronic constipation is very common at outpatient clinic. However, acute urinary retention and voiding difficulty caused by fecaloma in the giant Duhamel pouch has never been reported in Korea. We would like to present our case with acute urinary retention due to a fecaloma and suggest that fecaloma might be considered as one of the causes for acute urinary retention, especially in cases with previous Duhamel operation for repair of Hischsprung disease. PMID- 24224157 TI - Direct cell lysis for single-cell gene expression profiling. AB - The interest to analyze single and few cell samples is rapidly increasing. Numerous extraction protocols to purify nucleic acids are available, but most of them compromise severely on yield to remove contaminants and are therefore not suitable for the analysis of samples containing small numbers of transcripts only. Here, we evaluate 17 direct cell lysis protocols for transcript yield and compatibility with downstream reverse transcription quantitative real-time PCR. Four endogenously expressed genes are assayed together with RNA and DNA spikes in the samples. We found bovine serum albumin (BSA) to be the best lysis agent, resulting in efficient cell lysis, high RNA stability, and enhanced reverse transcription efficiency. Furthermore, we found direct cell lysis with BSA superior to standard column based extraction methods, when analyzing from 1 up to 512 mammalian cells. In conclusion, direct cell lysis protocols based on BSA can be applied with most cell collection methods and are compatible with most analytical workflows to analyze single-cells as well as samples composed of small numbers of cells. PMID- 24224156 TI - An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development. AB - APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID- 24224158 TI - Engineering production of functional scFv antibody in E. coli by co-expressing the molecule chaperone Skp. AB - Single-chain variable fragment (scFv) is a class of engineered antibodies generated by the fusion of the heavy (VH) and light chains (VL) of immunoglobulins through a short polypeptide linker. ScFv play a critical role in therapy and diagnosis of human diseases, and may in fact also be developed into a potential diagnostic and/or therapeutic agent. However, the fact that current scFv antibodies have poor stability, low solubility, and affinity, seriously limits their diagnostic and clinical implication. Here we have developed four different expression vectors, and evaluated their abilities to express a soluble scFv protein. The solubility and binding activity of the purified proteins were determined using both SDS-PAGE and ELISA. Amongst the four purified proteins, the Skp co-expressed scFv showed the highest solubility, and the binding activity to antigen TLH was 3-4 fold higher than the other three purified scFv. In fact, this scFv is specific for TLH and does not cross-react with other TLH-associated proteins and could be used to detect TLH directly in real samples. These results suggest that the pACYC-Duet-skp co-expression vector might be a useful tool for the production of soluble and functional scFv antibody. PMID- 24224159 TI - Human papillomavirus and oropharyngeal cancer in Greenland in 1994-2010. AB - BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is associated with the sexually transmitted human papillomavirus (HPV), smoking and alcohol. In Greenland, a high rate of HPV-induced cervical cancer and venereal diseases are found, which exposes the population for high risk of HPV infection. In Greenland, only girls are included in the mandatory HPV vaccination program. OBJECTIVE: To investigate the annual incidence of OPSCC and the proportion of HPV-associated OPSCC (HPV+ OPSCC) in Greenland in 1994-2010. DESIGN: At Rigshospitalet, University of Copenhagen, we identified all Greenlandic patients diagnosed and treated for OPSCC from 1994 to 2010. Sections were cut from the patient's paraffin-embedded tissue blocks and investigated for p16 expression by immunohistochemistry. HPV analyses were performed with 2 sets of general HPV primers and 1 set of HPV16-specific primer. HPV+ OPSCC was defined as both >75% p16+ cells and PCR positive for HPV. RESULTS: Of 26 Greenlandic patients diagnosed with OPSCC, 17 were males and 9 were females. The proportion of HPV+ OPSCC in the total study period was 22%, without significant changes in the population in Greenland. We found an increase in the proportion of HPV+ OPSCC from 14% in 1994-2001 to 25% in 2002-2010 (p=0.51). Among males from 20 to 27% (p=0.63) and in females from 0 to 20% (p=0.71). The annual OPSCC incidence increased from 2.3/100,000 (CI=1.2-4.2) in 1994-2001 to 3.8/100,000 (CI=2.4-6.2) in 2002-2010: among males from 2.4/100,000 (CI=1.0-5.7) to 5.0/100,000 (CI=2.9 8.9). CONCLUSION: Even though the population is at high risk of HPV infection, the proportion of 22% HPV+ OPSCC in the total study period is low compared to Europe and the United States. This might be explained by our small study size and/or by ethnic, geographical, sexual and cultural differences. Continuing observations of the OPSCC incidence and the proportion of HPV+ OPSCC in Greenland are needed. PMID- 24224160 TI - Prognostic value of combined aquaporin 3 and aquaporin 5 overexpression in hepatocellular carcinoma. AB - BACKGROUND: Aquaporin (AQP) 3 and AQP 5 are involved in tumorigenesis and tumor progression of several tumor types. AIM: To investigate expression patterns and clinical significance of AQP3 and AQP5 in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry was performed to detect the expression of AQP3 and AQP5 in HCC tissues. RESULTS: Immunohistochemistry analysis showed the increased expression of AQP3 and AQP5 protein levels in HCC tissues compared with their adjacent nonneoplastic tissues (both P < 0.001). In addition, combined AQP3 and AQP5 protein expression was significantly associated with serum AFP (P = 0.008), tumor stage (P = 0.006), and tumor grade (P = 0.006). Moreover, HCC patients highly expressing both AQP3 and AQP5 proteins had worse 5-year disease-free survival and 5-year overall survival (P = 0.002 and 0.005, resp.). Furthermore, the Cox proportional hazards model showed that combined AQP3 and AQP5 protein expression was an independent poor prognostic factor for both 5-year disease-free survival (P = 0.009) and 5-year overall survival (P = 0.01) in HCC. CONCLUSION: Our data suggest for the first time that the aberrant expression of AQP3 and AQP5 proteins may be strongly related to tumor progression and prognosis in patients with HCC. The overexpression of AQP3 in combination with upregulation of AQP5 may be an unfavorable prognostic factor for HCC. PMID- 24224161 TI - Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel. AB - The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 MUm. Gels of 20% Pluronic F127, which were liquid at or below 24.6 degrees C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6 degrees C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries. PMID- 24224162 TI - Postoperative adiponectin levels in pediatric patients undergoing open heart surgery. AB - BACKGROUND: Adipose tissue is an important endocrine organ that secretes cytokines, including adiponectin, levels of which are negatively correlated with the severity of the inflammatory process. Aim. To assess the time course of adiponectin levels following open heart surgery with cardiopulmonary bypass and its correlation with early postoperative outcomes. MATERIALS AND METHODS: Blood samples were obtained from 24 children undergoing cardiac surgery and analyzed for adiponectin, C-reactive protein, and other inflammatory markers. RESULTS: Baseline adiponectin levels were negatively correlated with patients' preoperative weight and age. Postoperative adiponectin levels decreased compared to baseline (P = 0.01) and correlated negatively with duration of cardiopulmonary bypass (r = -0.438, P = 0.037), length of stay in the pediatric intensive care unit (r = -0.457, P = 0.025), and the inotropic score (r = -0.471, P = 0.02). Adiponectin levels were positively correlated with sVCAM 1 levels; however, there was no correlation between adiponectin levels and sP selectin, tPA, MCP1, and sCD40. CONCLUSIONS: The inflammatory response after open heart surgery with cardiopulmonary bypass is associated with a reduction in adiponectin levels. Prolonged or more complicated surgery induced a more substantial inflammatory process characterized by a significant reduction in adiponectin levels over time and a delayed return to baseline levels. PMID- 24224163 TI - Body posture asymmetry differences between children with mild scoliosis and children with unilateral cerebral palsy. AB - Patients with unilateral cerebral palsy (CP) often have impaired movement coordination, reduced between-limb synchronization, and less weight bearing on the affected side, which can affect the maintenance of an upright weight-bearing position and gait. This study evaluated whether the different postural patterns of children with unilateral CP could be statistically recognized using cluster analysis. Forty-five outpatients with unilateral CP (mean age, 9 years and 5 months) and 51 able-bodied children with mild scoliosis (mean age, 9 years and 2 months) were included. One observer performed moire topography (MT) examinations using a CQ Electronic System (Poland) device. A weight distribution analysis on the base of support (BOS) between the body sides was performed simultaneously. A force plate dynamographic platform (PDM), ZEBRIS (Germany), with FootPrint software was used for these measurements. Cluster analysis revealed three groups: Cluster 1 (n = 71, 73.96%), Cluster 2 (n = 8, 8.33%), and Cluster 3 (n = 17, 17.71%). Based on the MT parameters (extracted using a data reduction technique), three typical asymmetrical postural patterns were described: (1) the postural pattern of children with mild scoliosis (SCOL), (2) the progravitational postural pattern (PGPP), and (3) the antigravitational pattern. Patterns two and three were identified in children with unilateral CP. PMID- 24224165 TI - Cardiometabolic diseases and related complications: current status and future perspective. PMID- 24224164 TI - Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract. AB - The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg 1) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150 mg kg-1. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release. PMID- 24224166 TI - Rare variants in the TREX1 gene and susceptibility to autoimmune diseases. AB - TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. PMID- 24224167 TI - Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues. AB - Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue. PMID- 24224168 TI - Essential oil of common sage (Salvia officinalis L.) from Jordan: assessment of safety in mammalian cells and its antifungal and anti-inflammatory potential. AB - Salvia officinalis L. (Lamiaceae) is a Mediterranean species, naturalized in many countries. In Jordan, it is used in traditional medicine as antiseptic, antiscabies, antisyphilitic, and anti-inflammatory, being frequently used against skin diseases. This study aimed the assessment of the antifungal and anti inflammatory potential of its essential oils, and their cytotoxicity on macrophages and keratinocytes. The oils were investigated by gas chromatography and gas chromatography-mass spectrometry and the antifungal activity was evaluated against yeasts, dermatophyte and Aspergillus strains. Assessment of cell viability was made by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay and the in vitro anti-inflammatory potential was evaluated by measuring nitric oxide production using lipopolysaccharide stimulated mouse macrophages. The main compounds of S. officinalis oils were 1,8 cineole (39.5-50.3%) and camphor (8.8-25.0%). The oils revealed antifungal activity against dermatophyte strains and significantly inhibited NO production stimulated by LPS in macrophages, without affecting cell viability, in concentrations up to 0.64 MUL/mL. This is the first report addressing the in vitro anti-inflammatory potential of S. officinalis oil. These findings demonstrated that bioactive concentrations of S. officinalis oils do not affect mammalian macrophages and keratinocytes viability making them suitable to be incorporated in skin care formulations for cosmetic and pharmaceutical purposes. PMID- 24224169 TI - Effect of Jatropha curcas peptide fractions on the angiotensin I-converting enzyme inhibitory activity. AB - Hypertension is one of the most common worldwide diseases in humans. Angiotensin I-converting enzyme (ACE) plays an important role in regulating blood pressure and hypertension. An evaluation was done on the effect of Alcalase hydrolysis of defatted Jatropha curcas kernel meal on ACE inhibitory activity in the resulting hydrolysate and its purified fractions. Alcalase exhibited broad specificity and produced a protein hydrolysate with a 21.35% degree of hydrolysis and 34.87% ACE inhibition. Ultrafiltration of the hydrolysate produced peptide fractions with increased biological activity (24.46-61.41%). Hydrophobic residues contributed substantially to the peptides' inhibitory potency. The 5-10 and <1 kDa fractions were selected for further fractionation by gel filtration chromatography. ACE inhibitory activity (%) ranged from 22.66 to 45.96% with the 5-10 kDa ultrafiltered fraction and from 36.91 to 55.83% with the <1 kDa ultrafiltered fraction. The highest ACE inhibitory activity was observed in F2 (IC50 = 6.7 MUg/mL) from the 5-10 kDa fraction and F1 (IC50 = 4.78 MUg/mL) from the <1 kDa fraction. ACE inhibitory fractions from Jatropha kernel have potential applications in alternative hypertension therapies, adding a new application for the Jatropha plant protein fraction and improving the financial viability and sustainability of a Jatropha-based biodiesel industry. PMID- 24224170 TI - Oligomannose-coated liposome as a novel adjuvant for the induction of cellular immune responses to control disease status. AB - Professional phagocytic cells, such as dendritic cells, are mainly responsible for phagocytosis, antigen presentation, and cytokine secretion, which induce subsequent activation of T cell-mediated immunity. Thus, strategies that deliver antigens and stimulatory signals to the cells have significant implications for vaccine design. In this paper, we summarize the potential for liposomes coated with the neoglycolipids containing oligomannose residues (OMLs) as a novel adjuvant for induction of Th1 immune responses and CTLs specific for the encased antigen. OMLs preferentially take up peripheral phagocytic cells. In response to OML uptake, the cells secrete IL-12 selectively, enhance the expression of costimulatory molecules, and migrate into lymphoid tissues from peripheral tissues. OMLs also have the ability to deliver encapsulated protein antigens to the MHC class I and class II pathways to generate antigen-specific CTLs and Th1 cells, respectively, and lipid antigen to CD1d to activate NKT cells. Since administration of OML-based vaccines can eliminate an established tumor, inhibit elevation of the serum IgE level, and prevent progression of protozoan infections in several murine, human, and bovine models, OML-based vaccines have revealed their potential for clinical use in vaccination for a variety of diseases in which CTLs and/or Th1 cells act as effector cells. PMID- 24224171 TI - Development of a modelling to correlate site and diameter of brain metastases with hippocampal sparing using volumetric modulated Arc therapy. AB - PURPOSE: To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA) technique on whole brain with simultaneously integrated boost (SIB). METHODS AND MATERIALS: An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions), and SIB doses to brain metastases were 63 Gy (2 and 3 cm) or 70.8 Gy (1 cm). Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. RESULTS: Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter's metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. CONCLUSIONS: Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations. PMID- 24224173 TI - An isolated medial patellofemoral ligament reconstruction with patellar tendon autograft. AB - The aim of the study was to evaluate the results of the medial patellofemoral ligament reconstruction with a medial strip of patellar tendon autograft after a minimum 2-year followup. Ten patients (10 knees) were operated on by one surgeon, according to the modified technique, described by Camanho, without any bone plug at free graft end. The mean age of the patients was 27.2 years (ranging from 18 to 42 years). The mean follow-up period was 3 years and 7 months. All patients were reviewed prospectively. At the last follow-up visit, all the patients demonstrated a significant improvement in terms of patellofemoral joint stability, all aspects of the KOOS questionnaire, and Kujala et al.'s score (59.7 points preoperatively and 84.4 points at the last followup). No patient revealed recurrent dislocation. The SF-36 score revealed a significant improvement in bodily pain, general health, physical role functioning, social role functioning, and physical functioning domains. The described MPFL reconstruction with the use of the medial 1/3rd of patella tendon is an effective procedure that gives satisfactorily patellofemoral joint functions, improves the quality of life, and provides much pain relief. It is relatively simple, surgically not extensive, and economically cost-effective procedure. PMID- 24224174 TI - Statistical fractal models based on GND-PCA and its application on classification of liver diseases. AB - A new method is proposed to establish the statistical fractal model for liver diseases classification. Firstly, the fractal theory is used to construct the high-order tensor, and then Generalized N-dimensional Principal Component Analysis (GND-PCA) is used to establish the statistical fractal model and select the feature from the region of liver; at the same time different features have different weights, and finally, Support Vector Machine Optimized Ant Colony (ACO SVM) algorithm is used to establish the classifier for the recognition of liver disease. In order to verify the effectiveness of the proposed method, PCA eigenface method and normal SVM method are chosen as the contrast methods. The experimental results show that the proposed method can reconstruct liver volume better and improve the classification accuracy of liver diseases. PMID- 24224172 TI - Potential effects of medicinal plants and secondary metabolites on acute lung injury. AB - Acute lung injury (ALI) is a life-threatening syndrome that causes high morbidity and mortality worldwide. ALI is characterized by increased permeability of the alveolar-capillary membrane, edema, uncontrolled neutrophils migration to the lung, and diffuse alveolar damage, leading to acute hypoxemic respiratory failure. Although corticosteroids remain the mainstay of ALI treatment, they cause significant side effects. Agents of natural origin, such as medicinal plants and their secondary metabolites, mainly those with very few side effects, could be excellent alternatives for ALI treatment. Several studies, including our own, have demonstrated that plant extracts and/or secondary metabolites isolated from them reduce most ALI phenotypes in experimental animal models, including neutrophil recruitment to the lung, the production of pro-inflammatory cytokines and chemokines, edema, and vascular permeability. In this review, we summarized these studies and described the anti-inflammatory activity of various plant extracts, such as Ginkgo biloba and Punica granatum, and such secondary metabolites as epigallocatechin-3-gallate and ellagic acid. In addition, we highlight the medical potential of these extracts and plant-derived compounds for treating of ALI. PMID- 24224175 TI - Effect of adjuvant magnetic fields in radiotherapy on non-small-cell lung cancer cells in vitro. AB - OBJECTIVES: To explore sensitization and possible mechanisms of adjuvant magnetic fields (MFs) in radiotherapy (RT) of non-small-cell lung cancer. METHODS: Human A549 lung adenocarcinoma cells were treated with MF, RT, and combined MF-RT. Colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by microarray. RESULTS: A 0.5 T, 8 Hz stationary MF showed a duration-dependent inhibitory effect lasting for 1-4 hours. The MF-treated groups had significantly greater cell inhibition than did controls (P < 0.05). Surviving fractions and growth curves derived from colony-forming assay showed that the MF-only, RT-only, and MF-RT groups had inhibited cell growth; the MF-RT group showed a synergetic effect. Microarray of A549 cells exposed for 1 hour to MF showed that 19 cell cycle- and apoptosis-related genes had 2-fold upregulation and 40 genes had 2 fold downregulation. MF significantly arrested cells in G2 and M phases, apparently sensitizing the cells to RT. CONCLUSIONS: MF may inhibit A549 cells and can increase their sensitivity to RT, possibly by affecting cell cycle- and apoptosis-related signaling pathways. PMID- 24224176 TI - How ocular surface disease impacts the glaucoma treatment outcome. AB - The treatment goals for glaucoma are lowering the intraocular pressure and preservation of vision. Topical hypotensive drops are the standard form of therapy which is often associated with some symptoms of toxicity, ocular inflammation, allergy, or ocular surface disease (OSD). OSD is a common comorbidity in glaucoma patients, and its prevalence with glaucoma increases with age. Use of topical treatment could additionally increase symptoms of OSD mostly due to preservatives added to multidose medication bottles used to reduce the risk of microbial contamination. This toxicity has been particularly associated with BAK, the most commonly used preservative which damages conjunctival and corneal epithelial cells and significantly aggravates OSD symptoms. OSD adversely affects patients' quality of life causing discomfort and problems with vision which in turn may result in noncompliance, lack of adherence, and eventually visual impairment. In the management of glaucoma patients OSD symptoms should not be overlooked. If they are present, topical glaucoma treatment should be adapted by decreasing the amount of drops instilled daily, using BAK-free or preservative free medication and lubricants if necessary. Awareness of the presence and importance of OSD will in turn improve patients' adherence and compliance and thus ultimately the preservation of long-term vision. PMID- 24224177 TI - Myricitrin inhibits acrylamide-mediated cytotoxicity in human Caco-2 cells by preventing oxidative stress. AB - Oxidative stress was thought to be associated with acrylamide cytotoxicity, but the link between oxidative stress and acrylamide cytotoxicity in the gastrointestinal tract, the primary organ in contact with dietary acrylamide, is still unclear. This study was conducted to evaluate the antioxidant activity of natural dietary compound myricitrin and its protective role against acrylamide cytotoxicity. We found that myricitrin can effectively scavenge multiple free radicals (including DPPH free radical, hydroxyl radical, and ABTS free radical) in a concentration-dependent manner. Our results further indicated that the presence of myricitrin (2.5-10 MUg/mL) was found to significantly inhibit acrylamide-induced cytotoxicity in human gastrointestinal Caco-2 cells. Moreover, acrylamide-induced cytotoxicity is closely related to oxidative stress in Caco-2 cells. Interestingly, myricitrin was able to suppress acrylamide toxicity by inhibiting ROS generation. Taken together, these results demonstrate that myricitrin had a profound antioxidant effect and can protect against acrylamide mediated cytotoxicity. PMID- 24224178 TI - The role of red blood cells in enhancing or preventing HIV infection and other diseases. AB - AIM: To highlight the apparently neglected role of erythrocyte antigens in the epidemiology of infectious diseases, especially HIV, with the prime objective of stimulating research in this area. METHOD: A literature search was performed on the PubMed for relevant papers from 1984 to 2013, the era covering active HIV research. This was achieved by using the phrases "erythrocyte blood groups HIV" (81 papers) or "red cell antigen, blood groups, and HIV" (60 papers). A manual Google Scholar search was done and supplemented by original papers referenced by various authors. However, the review was limited by the relative scarcity of papers on the subject, and only papers written in English were reviewed during the period October 2012 to September 2013. RESULTS: Many communicable and noncommunicable diseases are associated with specific blood groups. Examples of these diseases are discussed in detail. HIV has been shown to bind to erythrocytes, and candidate erythrocyte-binding molecules and mechanisms are also discussed. Moreover, erythrocyte-HIV binding is associated with increased viral infectivity, thus, underscoring the need to study this phenomenon and its implications for HIV epidemiology. CONCLUSION: Erythrocyte antigens may be important in the pathogenesis and epidemiology of many diseases, including HIV. PMID- 24224179 TI - Hybrid total knee arthroplasty revisited: midterm followup of hybrid versus cemented fixation in total knee arthroplasty. AB - The optimal method of fixation in total knee arthroplasty is still debated. Hybrid total knee arthroplasty (TKA), with cemented tibial and cementless femoral components, is a proposed method of fixation to improve outcomes. Although several studies have shown favorable outcomes, there is still lack of consensus in the literature. We hypothesized that hybrid TKA yields similar clinical, radiographic, and survivorship results compared to fully cemented TKA. The clinical and radiographic outcomes of 304 cruciate retaining TKAs with minimum two-year followup, including 193 hybrid (mean followup of 4.1 years) and fully cemented TKAs (mean followup of 3.2 years) were evaluated. Knee society scores were similar between the two groups. The total number of femoral radiolucencies was also similar between the two groups, while a greater number of femoral Zone 4 radiolucencies were seen in the cemented group (9% versus 1.6%, P = 0.005). The hybrid group demonstrated a 99.2% survival rate of the femoral component out to seven years for aseptic loosening. No significant difference in survivorship was seen between the groups for all cause or aseptic failure at seven years. We conclude that hybrid fixation leads to similar intermediate-term outcomes as fully cemented components and remains a viable option in total knee arthroplasty. PMID- 24224180 TI - Mixing energy models in genetic algorithms for on-lattice protein structure prediction. AB - Protein structure prediction (PSP) is computationally a very challenging problem. The challenge largely comes from the fact that the energy function that needs to be minimised in order to obtain the native structure of a given protein is not clearly known. A high resolution 20 * 20 energy model could better capture the behaviour of the actual energy function than a low resolution energy model such as hydrophobic polar. However, the fine grained details of the high resolution interaction energy matrix are often not very informative for guiding the search. In contrast, a low resolution energy model could effectively bias the search towards certain promising directions. In this paper, we develop a genetic algorithm that mainly uses a high resolution energy model for protein structure evaluation but uses a low resolution HP energy model in focussing the search towards exploring structures that have hydrophobic cores. We experimentally show that this mixing of energy models leads to significant lower energy structures compared to the state-of-the-art results. PMID- 24224181 TI - Household survey of pesticide practice, deliberate self-harm, and suicide in the Sundarban region of West Bengal, India. AB - The toxicological impact and intentional ingestion of pesticides are major public health concerns globally. This study aimed to estimate the extent of deliberate self-harm (DSH) and suicides (suicidal behaviour) and document pesticide practices in Namkhana block of the Sundarban region, India. A cross-sectional study was conducted in 1680 households (21 villages) following a mixed random and cluster design sampling. The survey questionnaire (Household Information on Pesticide Use and DSH) was developed by the research team to elicit qualitative and quantitative information. The Kappa statistic and McNemar's test were used to assess the level of agreement and association between respondents' and investigators' opinions about safe storage of pesticides. Over five years, 1680 households reported 181 incidents of suicidal behaviour. Conflict with family members was the most frequently reported reason for suicidal behaviour (53.6%). The Kappa statistic indicated poor agreement between respondents and investigators about safe storage of pesticides. The pesticide-related annual DSH rate was 158.1 (95% CI 126.2-195.5), and for suicide it was 73.4 (95% CI 52.2 100.3) per 100,000. Unsafe pesticide practice and psychosocial stressors are related to the high rates of suicidal behaviour. An intersectoral approach involving the local governments, agricultural department and the health sector would help to reduce the magnitude of this public health problem. PMID- 24224182 TI - Human Hepatocellular Carcinoma Metabolism: Imaging by Hyperpolarized 13C Magnetic Resonance Spectroscopy. AB - PURPOSE: Most cancers exhibit high levels of aerobic glycolytic metabolism with diminished levels of mitochondrial oxidative phosphorylation even in the presence of normal or near-normal levels of oxygen ("Warburg effect"). However, technical challenges have limited the development of non-invasive in vivo imaging techniques for monitoring glycolytic metabolism of hepatocellular carcinoma (HCC) and quantitatively evaluating the impact of this effect on the growth and therapy of this disease. Thus, there is a critical need to develop non-invasive techniques for longitudinal assessment of the metabolism and treatment response of patients with unresectable HCCs. PROCEDURES: This article discusses a novel method, "Hyperpolarized 13C MRS imaging", for achieving this objective and thus improving the prognosis of HCC patients. The primary objective has been to characterize in vivo metabolic biomarkers as determinants of HCC metabolism and treatment response of unresectable HCC tumors or viable HCC cells. RESULTS: This innovative technique capitalizes on a new technology that increases the sensitivity of MRS detection of crucial metabolites in cancer cells. CONCLUSION: It is anticipated that this innovative approach will lead to improved methods, both for the diagnosis and staging of HCCs and for the facilitation of the development of enzyme targeted therapies and other therapeutic interventions. PMID- 24224183 TI - Author response. PMID- 24224184 TI - Reply to Smith and Shortle: Lacking evidence of hydraulic efficiency changes. PMID- 24224185 TI - Reply to Rattenborg and Martinez-Gonzalez: Fundamental and divergent aspects of the neurobiology of episodic memory. PMID- 24224186 TI - Coronary artery bypass grafting: the past, present, and the future. PMID- 24224187 TI - The Aswan Heart Centre project. PMID- 24224188 TI - Polio eradication: where are we now? PMID- 24224189 TI - Authors' reply. PMID- 24224190 TI - Concerns raised over the UK's first private medical school. PMID- 24224191 TI - India Alliance promotes clinical and public health research. PMID- 24224192 TI - Googling a patient. PMID- 24224193 TI - Case study. Googling a patient. Commentary. PMID- 24224194 TI - Trauma safety-net hospitals will survive under the Affordable Care Act (ACA). PMID- 24224195 TI - Microglia actions in Alzheimer's disease. AB - The identification of microglia-associated, neurological disease-causing mutations in patients, combined with studies in mouse models has highlighted microglia, the brain's intrinsic myeloid cells, as key modulators of pathogenesis and disease progression in neurodegenerative diseases. In Alzheimer's disease (AD) in particular, the activation and accumulation of microglial cells around b Amyloid (Ab) plaques has long been described and is believed to result in chronic neuroinflammation-a term that, despite being commonly used, lacks a precise definition. This seemingly directed response of microglia to amyloid deposits conflicts with the fact that the increasing buildup of Ab plaques is not inhibited by these cells during disease progression. While recent evidence suggests that microglia lose their intrinsic beneficial function during the course of AD and may even acquire a ''toxic'' phenotype over time, Ab may also simply not be an appropriate trigger to induce phagocytosis and degradation by microglia in vivo. As recent experimental evidence has indicated the importance of the microglia in AD pathogenesis, future efforts aimed at tackling this disease via utilization or modulation of microglia or factors therefrom appear to be an exciting and challenging research front. PMID- 24224196 TI - 2014 Acta Biomaterialia Gold Medal Award. PMID- 24224197 TI - Image of the month: superior mesenteric artery syndrome. PMID- 24224198 TI - [Epidemiology of a cohort of 450 urolithiasis at the Yalgado Ouedraogo university hospital of Ouagadougou (Burkina Faso)]. AB - OBJECTIVE: To report the epidemiological and diagnosis characteristics of urolithiasis in the city of Ouagadougou (Burkina Faso). PATIENTS AND METHODS: We performed a retrospective and descriptive study of a cohort of urolithiasis patients from January 2009 to December 2011 at the department of urology of the Yalgado Ouedraogo University hospital of Ouagadougou. The minimum required data were: age, gender, occupation, residence, complete medical observation and medical imaging results. RESULTS: Four hundred and fifty patients with a median age of 35 years were included in this study. Urinary stones prevalence was 12.5%. There was a male predominance with a sex ratio of 1.91. Renal colic found in 32% of patients was the main pattern of consultation. Urinary schistosomiasis was the main etiological factor correlated with the occurrence of urolithiasis (P < 0.05). The majority of urinary stones in this study were located in the upper urinary tract (86.5%). Complications were dominated by urinary tract infections (45.2%) and obstructive renal failure (8.9%). CONCLUSION: The characteristics of urolithiasis in our center were similar to those reported in the developing world but seem to evolve toward those of industrialized countries. PMID- 24224199 TI - Author response. PMID- 24224200 TI - Alexander Monro, tertius (1773-1859). PMID- 24224201 TI - Author's reply: To PMID 23516702. PMID- 24224202 TI - Rounded atelectasis mimicking lung cancer. PMID- 24224203 TI - Sir Harry C Sinderson Pasha: additional comments. PMID- 24224204 TI - Scurvy and Scott's return from the South Pole. PMID- 24224205 TI - Author's reply: To PMID 23734365. PMID- 24224210 TI - Drug-induced methaemoglobinaemia. PMID- 24224209 TI - The difference between surgeons and physicians. PMID- 24224212 TI - Averting risk through effective population management. PMID- 24224211 TI - Managing the data explosion. PMID- 24224213 TI - Using EHRs appropriately: a team-based approach to clinical care. PMID- 24224214 TI - The state of HIE: one health system CIO's view. Interview by Mark Hagland. PMID- 24224215 TI - Virtual coaching: one health plan's clever weight loss program. PMID- 24224216 TI - Insights on preparing for impending deadline. Interview by Rajiv Leventhal. PMID- 24224217 TI - Many hospitals still lag in CPOE implementation. PMID- 24224218 TI - Optimizing EHR implementation through 'pre-load services'. Interview by Mark Hagland. PMID- 24224219 TI - Tackling ED violence with RTLS at Beaumont Health System. PMID- 24224221 TI - What's next? PMID- 24224220 TI - Does health IT have a staffing crisis? PMID- 24224222 TI - New season, new goals, and a new member challenge. PMID- 24224223 TI - National journal publishes TNA health care model. PMID- 24224224 TI - TNA examines mission, vision, and values. PMID- 24224225 TI - On the edge of the possible. PMID- 24224226 TI - Executive functioning: a scoping review of the occupational therapy literature. AB - BACKGROUND: Increasingly recognized as an important factor in the performance of complex, goal-directed tasks, executive functioning is understood in different ways across disciplines. PURPOSE: The aim was to explore the ways in which executive functioning is conceptualized, discussed, described, and implied in the occupational therapy literature. METHOD: A scoping review of the occupational therapy literature was conducted following Levac, Colquhoun, and O'Brien's (2010) recommended methodology. RESULTS: Executive functioning is described both as a set of performance component skills or processes and as the executive occupational performance inherent in complex occupations. Executive functioning is implicit in occupational performance and engagement, and some health conditions seem to be commonly associated with impaired executive functioning. Assessing executive functioning requires dynamic occupation- and performance based assessment. Interventions targeting executive functioning are grounded in metacognitive approaches. CONCLUSION: Executive functioning is a complex construct that is conceptualized with considerable variance within the occupational therapy literature, creating barriers to effective service delivery. PMID- 24224227 TI - Client-centred occupational therapy in Canada: refocusing on core values. AB - BACKGROUND: The Canadian occupational therapy profession has proclaimed its allegiance to client-centred practice for three decades. However, official definitions of client-centred practice have been inconsistent, and its defining features, underlying assumptions, and power relations have been subjected to little critical reflection. PURPOSE: The aim was to reflect critically on Canadian conceptions of client-centred practice and its core values. KEY ISSUES: Definitions of client-centred practice have evolved and changed, suggesting that the occupational therapy profession in Canada may have abandoned those values that originally underpinned its vision of client-centred practice by electing to focus on the enabling skills of therapists. However, evidence suggests that clients value those qualities of client-centred practice that underpinned the profession's original vision. IMPLICATIONS: This paper proposes a renewed focus on respect-respect for clients; respect for clients' strengths, experience, and knowledge; respect for clients' moral right to make choices concerning their lives-and on fostering respectful, supportive relationships with clients. PMID- 24224228 TI - A systematic review of yoga for state anxiety: considerations for occupational therapy. AB - BACKGROUND: State anxiety can result from a variety of life situations. This type of anxiety can disrupt occupational engagement and performance, thereby affecting rehabilitation and recovery. Occupational therapists need to address the connection between mind-body-spirit and its relationship to performance and engagement in meaningful occupations. Yoga, when used as an adjunct to therapy, has the potential to address state anxiety. PURPOSE: The aim was to systematically review the evidence concerning the effectiveness of yoga as a treatment approach for state anxiety. METHODS: Six electronic databases, the authors' own files, and the references of included studies from 1990 to July 2011 were searched. FINDINGS: A total of 25 unique studies represented by 26 publications made up the sample: two systematic reviews; 16 randomized controlled trials, and seven prospective, controlled, non-randomized studies. Evidence suggests yoga can be a viable therapeutic option for reducing state anxiety in certain situations. IMPLICATIONS: In making the determination to recommend yoga as an intervention, occupational therapists should consider the client's circumstances and values as well as the type and intensity of the yoga program. PMID- 24224229 TI - Examining the construct validity of the Cognitive Competency Test for occupational therapy practice. AB - BACKGROUND: Enhancing occupational therapy practice requires critical examination of assessment tools and the conclusions being drawn from their use. When working with cognitively impaired older individuals, judgments about occupational competence are often informed by an assessment of cognitive competence. PURPOSE: The Cognitive Competency Test (CCT) is a frequently used measure in Canada to inform predictions of occupational competence. However, there is an absence of published evidence that addresses its validity. METHODS: To appraise validity of the CCT, a retrospective chart review (n = 107) of CCT reports for inpatient and outpatient clients with cognitive impairment was conducted. Data were subjected to exploratory factor analyses to examine the factor structure, and the measure was compared with commonly used clinical variables reflecting cognitive and occupational competence. FINDINGS: Results suggest that the CCT measures a unitary construct and provide some support for its predictive capacity. IMPLICATIONS: CCT scores can add incremental validity to cognitive screens, such as the Mini Mental State Exam, when evaluating occupational competence. PMID- 24224230 TI - Advancing the use of theory in occupational therapy: a collaborative process. AB - BACKGROUND: Theory is important to the growth and evolution of occupational therapy. However, use of theory remains challenging for many therapists. PURPOSE: The aim was to develop a process that occupational therapists could apply to advance theory in practice. METHOD: Based on a review of the literature and using a qualitative instrumental case study design, 18 student occupational therapists and eight fieldwork educators completed online modules on the theory advancement concepts generated from the literature, wrote journals, and/or participated in online discussions during fieldwork. Following fieldwork, educators were interviewed and students participated in focus groups exploring their experiences. Directed content analysis was used to analyze the data. FINDINGS: Based on the data collected, we developed the Theory Advancement Process (TAP). The TAP is composed of four primary contexts, a climate of collaborative relationships with four key elements, and four essential processes. IMPLICATIONS: The TAP presents a collaborative process for students, faculty, and therapists to work together to advance the use of theory in practice. PMID- 24224231 TI - Which kinds of models are useful and which are not. PMID- 24224232 TI - Reply: To PMID 23156140. PMID- 24224233 TI - Effect of Bt maize and soil insecticides on yield, injury, and rootworm survival: implications for resistance management. AB - A 2-yr field experiment was conducted to determine the effects on Diabrotica spp. (Coleoptera: Chrysomelidae) of an insecticidal seed treatment (Poncho 1250, (AI)/clothianidin) and a granular insecticide (Aztec 2.1G, (AI)/tebupirimphos and cyfluthrin) alone and in combination with maize producing the insectidical toxin Cry3Bb1 derived from the bacterium Bacillus thuringiensis (Bt). Yields for Bt maize plots were significantly greater than for non-Bt maize; however, insecticides did not significantly affect yield. Insecticides significantly decreased root injury in non-Bt maize plots, but there were no significant differences in root injury between Bt maize with or without either insecticide. Maize producing the Bt toxin Cry3Bb1 and the soil-applied insecticide Aztec significantly decreased survival of western corn rootworm (Diabrotica virgifera virgifera LeConte), while only Bt maize significantly decreased survival of the northern corn rootworm (Diabrotica barberi Smith & Lawrence). For both species, Bt maize and each of the insecticides delayed emergence. In the absence of density-dependent mortality, Bt maize imposed 71 and 80% reduction in survival on the western corn rootworm and the northern corn rootworm, respectively. The data from this study do not support combining insecticide with Bt maize because the addition of insecticide did not increase yield or reduce root injury for Bt maize, and the level of rootworm mortality achieved with conventional insecticide was likely too low to delay the evolution of Bt resistance. In addition, delays in emergence from Bt maize combined with insecticides could promote assortative mating among Bt-selected individuals, which may hasten resistance evolution. PMID- 24224234 TI - Effect of a fungicide and spray adjuvant on queen-rearing success in honey bees (Hymenoptera: Apidae). AB - Commercial producers of honey bee queens (Apis mellifera L.) have reported unexplained loss of immature queens during the larval or pupal stage. Many affected queen-rearing operations are situated among the almond orchards of California and report these losses in weeks after almond trees bloom. Almond flowers are a rich foraging resource for bees, but are often treated with fungicides, insecticides, and spray adjuvants during bloom. Anecdotal reports by queen producers associate problems in queen development with application of the fungicide Pristine (boscalid and pyraclostrobin) and spray adjuvants that are tank-mixed with it. To test the effect of these compounds on queen development, a new bioassay was developed in which queens are reared in closed swarm boxes for 4 d, until capping, with nurse bees fed exclusively on artificially contaminated pollen. Pollen was treated with four concentrations of formulated Pristine (0.4, 4, 40, and 400 ppm), a spray adjuvant (Break-Thru, 200 ppm), the combination of Pristine and spray adjuvant (400:200 ppm), the insect growth regulator insecticide diflubenzuron (100 ppm) as a positive control, or water as negative control. Chemical analysis revealed that low concentrations of pyraclostrobin (50 ppb), but no boscalid, were detectable in royal jelly secreted by nurse bees feeding on treated pollen. No significant difference in queen development or survival was observed between any of the experimental treatments and the negative control. Only diflubenzuron, the positive control, caused a substantial reduction in survival of immature queens. PMID- 24224235 TI - Geographical influences on content of 10-hydroxy-trans-2-decenoic acid in royal jelly in China. AB - The content of 10-hydroxy-trans-2-decenoic acid (10-HDA), a marker compound in royal jelly (RJ), is the most important criterion in grading RJ for commercial trade and varies with its origin. To identify the effect of geographical origin on 10-HDA content in RJ, 138 samples were collected from 19 provinces of China (divided into three groups) produced by either Apis mellifera ligustica Spinola, 1806 or a hybrid of A. m. ligustica and Apis mellifera carnica Pollman, 1879 and analyzed for moisture, sugar, crude protein, ash, acid, and 10-HDA concentration. The results show that RJ from western China has a significantly higher 10-HDA level (2.01 +/- 0.05%) than those from northeastern (1.87 +/- 0.05%) and eastern (1.75 +/- 0.03%) China. RJ secreted by hybrid bees contained more 10-HDA (1.89 +/ 0.03%) than that secreted by A. m. ligustica (1.78 +/- 0.03%). The 10-HDA content of RJ produced during flowering of rape (Brassica campestris L.), lime (Tilia amurensis Ruprecht), and vitex (Vitex negundo L. variety heterophylla (Franch.) Rehder) was 1.92, 1.80, and 1.68%, respectively. The results would be helpful during the process of price determination of RJ by providing some basis of geographical, bee strain, and botanical information for commercial trade. PMID- 24224236 TI - "Candidatus Liberibacter solanacearum" titer over time in Bactericera cockerelli (Hemiptera: Triozidae) after acquisition from infected potato and tomato plants. AB - The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a serious pest of potato and other solanaceous crops. B. cockerelli has been associated with the bacterium "Candidatus Liberibacter solanacearum" (Lso), the causal agent of zebra chip, a new and economically important disease of potato in the United States, Mexico, Central America, and New Zealand. The biology of liberibacter transmission to potato and other host plants by the potato psyllid is largely unknown. The current study determined Lso acquisition by adult psyllids following different acquisition access periods (AAP) on potato and tomato, quantified Lso titer over time in postacquisition psyllids, determined Lso-acquisition rate in psyllids at each AAP on each source of inoculum, and determined influence of host plant Lso titer on Lso acquisition rates and postacquisition titer in psyllids over time. Results showed that Lso detection rates and titer increased over time in psyllids following AAPs of 8, 24, and 72 h on tomato and potato and Lso titer was highest when psyllids acquired Lso from tomato versus potato. Lso titer ranged from 200- to 400-fold higher in tomato leaves, petioles, and stems than those of potato. The increase of Lso titer in the insects reached a plateau after an average of 15 d following 24 and 72 h AAP on potato or tomato. At this 15-d plateau, Lso titer in postacquisition psyllids was comparable with that of infective psyllids from the Lso-infected laboratory colony. Lso-acquisition rate in psyllids fed on potato and tomato increased up to 5 and 20, 15 and 35, 35 and 75, and 80 and 100%, respectively, when the insects were allowed access to plants for 4, 8, 24, and 72 h, respectively. PMID- 24224237 TI - Effect of aggregation pheromone trap of Riptortus pedestris (Hemiptera: Alydidae) on the distribution and composition of its egg parasitoids. AB - The aggregation pheromone of Riptortus pedestris (F.) (Hemiptera: Alydidae) is known to attract its egg parasitoids Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae) and Gryon japonicum (Ashmead) (Hymenoptera: Scelionidae). Distribution and composition of these egg parasitoids were compared in a soybean field in the presence and absence of aggregation pheromone-baited traps for two consecutive years. Three traps were installed on the edge of a soybean field, first without and then with aggregation pheromone in a before-after design, and changes in parasitism were assessed on nonviable host eggs released at distances of 9, 18, 27, and 36 m from the trap. A significant interactive effect of pheromone installation and distance was found in egg parasitism by both parasitoids. Parasitism on eggs recovered from 9 m away was up to 2.2 and 3.2 times higher in presence of pheromone than without pheromone for O. nezarae and G. japonicum, respectively. Parasitism by O. nezarae was always higher than that by G. japonicum, but their relative abundance, clutch size, and sex ratio were not affected by pheromone installation, irrespective of distance from the trap. In conclusion, aggregation pheromone increases abundance of parasitoids up to 18 m from trap installation points and does not affect the relative abundance of parasitoid species. PMID- 24224238 TI - Biology and rearing of Cleruchoides noackae (Hymenoptera: Mymaridae), an egg parasitoid for the biological control of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae). AB - Cleruchoides noackae Lin and Huber (Hymenoptera: Mymaridae) is a solitary egg parasitoid of Thaumastocoris peregrinus Carpintero and Dellape (Hemiptera: Thaumastocoridae). The parasitoid was first described in 2009 and its biology and rearing are poorly understood. A key obstacle to the use of C. noackae as a biological control agent has been the ability to consistently rear it under quarantine conditions. This study reports on a series of experiments conducted in quarantine to rear C. noackae and to examine the effects of diet on longevity, per capita reproduction, and progeny sex ratio, as well as to determine development time, and preference and suitability of host eggs of different ages. When supplemented with honey solution, the longevity of C. noackae females increased significantly by 2.4 d and that of males by 1.7 d, relative to the unfed adults. Mean per capita reproduction for the honey-fed wasps was 7.7 offspring per female, with progeny sex ratio slightly skewed toward males. Mean percentage parasitism was 32.2%. C. noackae was capable of parasitizing and completing development from oviposition to adult eclosion within 15.7 d in host eggs between 0 and 5 d old. The ability of C. noackae to parasitize a wide range of host egg ages increases the period of vulnerability of T. peregrinus to attack, increasing its potential efficacy as a biological control agent. The methods and results reported here represent a crucial step in the ongoing efforts to develop this potential biological control system. PMID- 24224239 TI - Evaluation of Beauveria bassiana for management of citrus thrips (Thysanoptera: Thripidae) in California blueberries. AB - Citrus thrips, Scirtothrips citri (Moulton), is a plant-feeding pest most widely recognized for causing damage to citrus and mango fruits. This insect has broadened its host range to become a significant pest of commercial blueberries grown in the San Joaquin Valley of California. We evaluated Beauveria bassiana (Balsamo) for control of citrus thrips in blueberries grown under two watering regimes (drip irrigation with and without overhead sprinklers) and using two fungal formulations (commercially available spores in suspension vs. colonized seed) over two sampling periods, that is, for two 3-d periods after treatment. We found significant differences in thrips densities as a function of water regime treatment and fungal formulation. Thrips levels were reduced significantly with both fungal treatments at 3 d after treatment, but at 6 d, only results with colonized seed differed from the control treatment. These data suggest entomopathogenic fungi might be useful for control of citrus thrips on blueberries in particular situations (in organic production or as a resistance management tool) but that traditional pesticides will likely remain the preferred management option. PMID- 24224240 TI - Releases of insectary-reared Galendromus occidentalis (Acari: Phytoseiidae) in commercial apple orchards. AB - Galendromus occidentalis (Nesbitt) is one of several phytoseiid species that are available for purchase to supplement endemic predator populations that are not providing sufficient control of spider mites. We performed a series of releases of commercially reared G. occidentalis in commercial apple (Malus domestica Borkhausen) orchards in Washington from 2010 to 2012. Releases of up to 50,000 mites per acre did not lead to an increase in populations of predatory mites or to a decrease in populations of pest mites. Assessments of mite numbers in shipments and quality (survival and fecundity) of those mites indicated that the commercial insectary was correctly estimating the number of predatory mites in their shipments, and that predator quality was not different than a laboratory colony. Finally, a predator-prey model that used the intrinsic rates of increase of tetranychid prey and the prey consumption rate of the predator indicated that the density of G. occidentalis required to control the prey at the action threshold was not economically feasible. We conclude that G. occidentalis cannot be used to bring about short-term control via inundative releases in crops such as apple with large canopy volumes. PMID- 24224241 TI - Development and validation of a quick easily used biochemical assay for evaluating the viability of small immobile arthropods. AB - Quickly, accurately, and easily assessing the efficacy of treatments to control sessile arthropods (e.g., scale insects) and stationary immature life stages (e.g., eggs and pupae) is problematic because it is difficult to tell whether treated organisms are alive or dead. Current approaches usually involve either maintaining organisms in the laboratory to observe them for development, gauging their response to physical stimulation, or assessing morphological characters such as turgidity and color. These can be slow, technically difficult, or subjective, and the validity of methods other than laboratory rearing has seldom been tested. Here, we describe development and validation of a quick easily used biochemical colorimetric assay for measuring the viability of arthropods that is sufficiently sensitive to test even very small organisms such as white fly eggs. The assay was adapted from a technique for staining the enzyme hexokinase to signal the presence of adenosine triphosphate in viable specimens by reducing a tetrazolium salt to formazan. Basic laboratory facilities and skills are required for production of the stain, but no specialist equipment, expertise, or facilities are needed for its use. PMID- 24224242 TI - Influence of modified atmosphere packaging on radiation tolerance in the phytosanitary pest melon fly (Diptera: Tephritidae). AB - Modified atmosphere packaging (MAP) produces a low-oxygen (O2) environment that can increase produce shelf life by decreasing product respiration and growth of pathogens. However, low O2 is known to increase insect tolerance to irradiation, and the use of MAP with products treated by irradiation before export to control quarantine pests may inadvertently compromise treatment efficacy. Melon fly, Bactrocera cucurbitae Coquillet (Diptera: Tephritidae), is an important economic and quarantine pest of tropical fruits and vegetables, and one of the most radiation-tolerant tephritid fruit flies known. The effect of low O2 generated by MAP on the radiation tolerance of B. cucurbitae was examined. Third-instar larval B. cucurbitae were inoculated into ripe papayas and treated by 1) MAP + irradiation, 2) irradiation alone, 3) MAP alone, or (4) no MAP and no irradiation, and held for adult emergence. Three types of commercially available MAP products were tested that produced O2 concentrations between 1 and 15%, and a sublethal radiation dose (50 Gy) was used to allow comparisons between treatments. Ziploc storage bags (1-4% O2) increased survivorship to adult from 14 to 25%, whereas Xtend PP61 bags (3-8% O2) and Xtend PP53 bags (11-15% O2) did not enhance survivorship to the adult stage in B. cucurbitae irradiated at 50 Gy. Radiation doses approved by the United States Department of Agriculture and the International Plant Protection Commission for B. cucurbitae and Ceratitis capitata (Wiedemann) (Mediterranean fruit fly) are 150 and 100 Gy, respectively. In large-scale tests, 9,000 B. cucurbitae and 3,800 C. capitata larvae infesting papayas in Ziploc bags were irradiated at 150 and 100 Gy, respectively, with no survivors to the adult stage. MAP can increase insect survivorship during irradiation treatment at certain doses and O2 concentrations, but should not compromise the efficacy of the 150-Gy generic radiation treatment for tephritid fruit flies or the 100-Gy radiation treatment for C. capitata. PMID- 24224243 TI - Factors influencing the abundance of pests in production fields and rates of interception of Dracaena marginata imported from Costa Rica. AB - Importation of live nursery plants, like Dracaena marginata Lamoureux (Ruscaceae), can provide a significant pathway for the entry of foliar pests from overseas into the United States. We studied the abundance of foliar pests of quarantine importance found on Costa Rican-grown D. marginata. These include five genera of leafhoppers (Heteroptera: Cicadellidae, Oncometopia, Caldweliola, Diestostema, Cypona, and Empoasca), Florida red scale (Heteroptera: Disapididae, Chrysomphalus aoinidum (L.)), katydids (Orthoptera: Tettigoniidae), and a snail (Succinea costarricana von Martens (Gastropoda, Stylommatophora, Succineidae)). In our first study, we examined the rationale behind size restrictions on Dracaena cuttings imported into the United States from Costa Rica. When comparing plant size, no differences were found in the abundance of quarantined pests on small (15-46 cm), medium (46-81 cm), and large (81-152 cm) propagules. In a second study, we estimated monthly abundances of pests in production plots for 1 yr to determine their relationship to rates of interception at U.S. ports. In any given month, < 6% of the marketable shoots standing in the field were infested with at least one quarantine pest. There was no relationship between the average monthly frequencies of pest detection in the field and in U.S. inspection ports. Pest detections increased during the 1 mo when average monthly shipments were abnormally high. Our data suggest that off-shore postprocessing efforts to remove pest-infested material from the market stream need to be adjusted to accommodate sharp increases in the volume of shipped plants. PMID- 24224244 TI - Cold storage enhances the efficacy and margin of security in postharvest irradiation treatments against fruit flies (Diptera: Tephritidae). AB - Cold storage is used to preserve fruit quality after harvest during transportation in marketing channels. Low temperature can be a stressor for insects that reduces survivorship, and cold storage may contribute to the efficacy of postharvest quarantine treatments such as irradiation against quarantine insect pests. The combined effect of irradiation and cold storage was examined in a radiation-tolerant fruit fly, Bactrocera cucurbitae Coquillet (melon fly), and a radiation-intolerant fruit fly, Ceratitis capitata (Wiedemann) (Mediterranean fruit fly) (Diptera: Tephritidae). Third instars on diet or in papaya were treated with a sublethal radiation dose of 30 Gy and stored at 4 or 11 degrees C for 3-13 d and held for adult emergence. For both fruit fly species, survival of third instars to the adult stage generally decreased with increasing cold storage duration at 4 or 11 degrees C in diet or papaya. Survivorship differences were highly significant for the effects of substrate (diet > papaya), temperature (11 > 4 degrees C),and irradiation (0 > 30 Gy). Few Mediterranean fruit flies survived in any cold storage treatment after receiving a radiation dose of 30 Gy. No melon fly larvae survived to the adult stage after irradiation and 11 d cold storage at 4 or 11 degrees C in papayas. Cold storage enhances the efficacy and widens the margin of security in postharvest irradiation treatments. Potentially irradiation and cold storage can be used in combination to reduce the irradiation exposure requirements of quarantine treatments. PMID- 24224245 TI - Flight performance of the orange wheat blossom midge (Diptera: Cecidomyiidae). AB - The orange wheat blossom midge, Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae), is a chronic wheat pest worldwide. Adult S. mosellana engage in short-distance flight, but also exploit weather patterns for long-distance dispersal. However, little is known about the flight performance of S. mosellana, and the effects of the biotic and abiotic factors that influence its flight activity. In this study, we explored the active flight potential of S. mosellana under various environmental factors using a 26-channel computer-monitored flight mill system. The most suitable temperature for flight and flight distance was 16 24 degrees C; flight duration peaked at 16 degrees C while speed peaked at 28 degrees C. Flight performance gradually declined between 10 and 400 lux light intensity. More than 50% individuals of 1-d-old females flew > 500 m, while only 24% of males flew > 500 m. One-day-old S. mosellana had stronger flight ability than that of 2-d-old individuals. This research showed that S. mosellana possessed strong enough flight ability that they can fly to a high altitude and then disperse via moving air currents. These results can aid in forecasting S. mosellana outbreak. PMID- 24224246 TI - Effects of Japanese beetle (Coleoptera: Scarabaeidae) and silk clipping in field corn. AB - Japanese beetle (Popillia japonica Newman) is an emerging silk-feeding insect found in fields in the lower Corn Belt and Midsouthern United States. Studies were conducted in 2010 and 2011 to evaluate how silk clipping in corn affects pollination and yield parameters. Manually clipping silks once daily had modest effects on yield parameters. Sustained clipping by either manually clipping silks three times per day or by caging Japanese beetles onto ears affected total kernel weight if it occurred during early silking (R1 growth stage). Manually clipping silks three times per day for the first 5 d of silking affected the number of kernels per ear, total kernel weight, and the weight of individual kernels. Caged beetles fed on silks and, depending on the number of beetles caged per ear, reduced the number of kernels per ear. Caging eight beetles per ear significantly reduced total kernel weight compared with noninfested ears. Drought stress before anthesis appeared to magnify the impact of silk clipping by Japanese beetles. There was evidence of some compensation for reduced pollination by increasing the size of pollinated kernels within the ear. Our results showed that it requires sustained silk clipping during the first week of silking to have substantial impacts on pollination and yield parameters, at least under good growing conditions. Some states recommend treating for Japanese beetle when three Japanese beetles per ear are found, silks are clipped to < 13 mm, and pollination is < 50% complete, and that recommendation appears to be adequate. PMID- 24224247 TI - Evaluation of inflorescence visitors as pollinators of Echinacea angustifolia (Asteraceae): comparison of techniques. AB - Inflorescences (heads or capitula) of the putative self-incompatible species, purple coneflower (Echinacea angustifolia (DC) Cronq. (Asteraceae)), were visited by insects representing the Coleoptera, Diptera, Hymenoptera, and Lepidoptera, in accordance with a generalist pollination syndrome. Measurement of the effectiveness of insect species as pollinators was accomplished by permitting solitary visits to receptive, central disc florets of virgin (previously bagged) heads. Four parameters were quantified: total stigmatic pollen load and proportion of pollen grains germinated, numbers of pollen tubes at style bases, and percentages of total receptive florets that had retracted (shrivelled) styles. Quantifying total and germinated pollen grains proved ineffective, partly owing to the tendency of self-pollen to initiate pollen tubes. The most effective pollinators were Apidae, especially bumble bees (Bombus spp.) and the European honey bee (Apis mellifera L.) (mean: 39 - 61% of styles retracted). Other noteworthy pollinators were cloudless sulfur butterflies (Phoebis sennae L.- Pieridae; mean 47% of style bases with pollen tubes), golden blister beetles (Epicauta ferruginea Say--Meloidae; 44%), and grasshopper bee flies (Systoechus vulgaris Loew--Bombyliidae; 22%). Sunflower leafcutter bees (Megachile pugnata Say) were less effective (4% of styles retracted). Promisingly, analysis of the proportion of retracted styles provided similar results to the established technique of pollen-tube quantification, but had the significant advantages of being completed more rapidly, without a microscope, and in the field. The quantitative technique of retracted-style analysis appears well suited for prompt measurement of inflorescence-visiting insects as pollinators of many asteraceans. PMID- 24224248 TI - The potential for controlling Pangaeus bilineatus (Heteroptera: Cydnidae) using a combination of entomopathogens and an insecticide. AB - The peanut burrower bug, Pangaeus bilineatus (Say), is an important pest of peanut (Arachis hypogaea L.) in the southern United States. Current control methods for this pest, which are based on the use of chemical insecticides, have not been successful. Our objective was to determine if entomopathogens applied alone or in combination with a standard chemical insecticide would provide superior levels of P. bilineatus mortality compared with the standard chemical applied alone. Specifically, we investigated the efficacy of an entomopathogenic nematode, Heterorhabditis bacteriophora Poinar (Oswego strain), and a fungus, Beauveria bassiana (Balsamo) Vuillemin (GHA strain), applied alone or in combination with chlorpyrifos. When applied as single treatments, the two entomopathogens were not pathogenic, that is, they did not cause mortality in P. bilineatus adults that was different from the nontreated control. However, 3 and 7 d posttreatment, the combination of the H. bacteriophora and chlorpyrifos caused higher mortality than the nematode, fungus, or insecticide alone, or the combination of chlorpyrifos and B. bassiana. The nature of the interaction between H. bacteriophora and chlorpyrifos was synergistic, which is of particular interest, given that this is the first time a synergy is being reported between a nematode that was not pathogenic when applied alone and a chemical insecticide. B. bassiana and its combination with the chlorpyrifos did not significantly increase insect mortality compared with chlorpyrifos alone or the control. Based on the observation of synergy, the combination of H. bacteriophora and chlorpyrifos should be investigated further for potential adoption in the management of P. bilineatus. PMID- 24224249 TI - Plant growth stage-specific injury and economic injury level for verde plant bug, Creontiades signatus (Hemiptera: Miridae), on cotton: effect of bloom period of infestation. AB - Verde plant bugs, Creontiades signatus Distant (Hemiptera: Miridae), were released onto caged cotton, Cossypium hirsutum L., for a 1-wk period to characterize the effects of insect density and bloom period of infestation on cotton injury and yield in 2011 and 2012, Corpus Christi, TX. When plants were infested during early bloom (10-11 nodes above first white flower), a linear decline in fruit retention and boll load and a linear increase in boll injury were detected as verde plant bug infestation levels increased from an average of 0.5 to 4 bugs per plant. Lint and seed yield per plant showed a corresponding decline. Fruit retention, boll load, and yield were not affected on plants infested 1 wk later at peak bloom (8-9 nodes above first white flower), even though boll injury increased as infestation levels increased. Second-year testing verified boll injury but not yield loss, when infestations occurred at peak bloom. Incidence of cotton boll rot, known to be associated with verde plant bug feeding, was low to modest (< 1% [2012] to 12% [2011] of bolls with disease symptoms), and drought stress persisted throughout the study. Caging effect was minimal: a 10% fruit retention decline was associated with caging, and the effect was not detectable in the other measurements. Overall, reduced fruit retention and boll load caused by verde plant bug were important contributors to yield decline, damage potential was greatest during the early bloom period of infestation, and a simple linear response best described the yield response insect density relationship at early bloom. Confirmation that cotton after peak bloom was less prone to verde plant bug injury and an early bloom-specific economic injury level were key findings that can improve integrated pest management decision-making for dryland cotton, at least under low-rainfall growing conditions. PMID- 24224250 TI - The distribution of European corn borer (Lepidoptera: Crambidae) moths in pivot irrigated corn. AB - The European corn borer, Ostrinia nubilalis (Hubner), is a damaging pest of numerous crops including corn, potato, and cotton. An understanding of the interaction between O. nubilalis and its spatial environment may aid in developing pest management strategy. Over a 2-yr period, approximately 8,000 pheromone trap catches of O. nubilalis were recorded on pivot-irrigated corn in northeastern Colorado. The highest weekly moth capture per pivot-irrigated field occurred on the week of 15 July 1997 at 1,803 moths captured. The lowest peak moth capture per pivot-irrigated field was recorded on the week of 4 June 1998 at 220 moths captured. Average trap catch per field ranged from approximately 1.6 moths captured per trap per week in 1997 to approximately 0.3 moths captured per trap per week in 1998. Using pheromone trap moth capture data, we developed a quantified understanding of the spatial distribution of adult male moths. Our findings suggest strong correlations between moth density and adjacent corn crops, prevailing wind direction, and an edge effect. In addition, directional component effects suggest that more moths were attracted to the southwestern portion of the crop, which has the greatest insolation potential. In addition to the tested predictor variables, we found a strong spatial autocorrelation signal indicating positive aggregations of these moths and that males from both inside and outside of the field are being attracted to within-field pheromone traps, which has implications for refuge strategy management. PMID- 24224251 TI - Effect of chipping on emergence of the redbay ambrosia beetle (Coleoptera: Curculionidae: Scolytinae) and recovery of the laurel wilt pathogen from infested wood chips. AB - Significant mortality ofredbay trees (Persea borbonia (L.) Spreng.) in the southeastern United States has been caused by Raffaelea lauricola, T.C. Harr., Fraedrich, & Aghayeva (Harrington et al. 2008), a fungal symbiont of the exotic redbay ambrosia beetle, Xyleborus glabratus, Eichhoff (Fraedrich et al. 2008). This pathogen causes laurel wilt, which is an irreversible disease that can kill mature trees within a few weeks in summer. R. lauricola has been shown to be lethal to most native species of Lauraceae and cultivated avocado (Persea americana Mill.) in the southeastern United States. In this study, we examined the survival of X. glabratus and R. lauricola in wood chips made from infested trees by using a standard tree chipper over a 10-wk period. After 2 wk, 14 X. glabratus were recovered from wood chips, whereas 339 X. glabratus emerged from nonchipped bolts. R. lauricola was not found 2 d postchipping from wood chips, indicating that the pathogen is not likely to survive for long inside wood chips. In contrast, R. lauricola persisted in dead, standing redbay trees for 14 mo. With large volumes of wood, the potential for infested logs to be moved between states or across U.S. borders is significant. Results demonstrated that chipping wood from laurel wilt-killed trees can significantly reduce the number of X. glabratus and limit the persistence of R. lauricola, which is important for sanitation strategies aimed at limiting the spread of this disease. PMID- 24224252 TI - Effects of ambient temperature on egg and larval development of the invasive emerald ash borer (Coleoptera: Buprestidae): implications for laboratory rearing. AB - The emerald ash borer, Agrilus planipennis Fairmaire, an invasive beetle from Asia causing large scale ash (Fraxinus) mortality in North America, has been extremely difficult to rear in the laboratory because of its long life cycle and cryptic nature of immature stages. This lack of effective laboratory-rearing methods has not only hindered research into its biology and ecology, but also mass production of natural enemies for biological control of this invasive pest. Using sticks from the alternate host plant, Fraxinus uhdei (Wenzig) Lingelsh, we characterized the stage-specific development time and growth rate of both emerald ash borer eggs and larvae at different constant temperatures (12-35 degrees C) for the purpose of developing effective laboratory-rearing methods. Results from our study showed that the median time for egg hatching decreased from 20 d at 20 degrees C to 7 d at 35 degrees C, while no emerald ash borer eggs hatched at 12 degrees C. The developmental time for 50% of emerald ash borer larvae advancing to third, fourth, and J-larval stages at 20 degrees C were 8.3, 9.1, and 12.3 wk, respectively, approximately two times longer than at 30 degrees C for the corresponding instars or stages. In contrast to 30 degrees C, however, the development times of emerald ash borer larvae advancing to later instars (from oviposition) were significantly increased at 35 degrees C, indicating adverse effects of this high temperature. The optimal range of ambient temperature to rear emerald ash borer larvae should be between 25-30 degrees C; however, faster rate of egg and larval development should be expected as temperature increases within this range. PMID- 24224253 TI - Captures of Rhagoletis indifferens (Diptera: Tephritidae) and nontarget insects on red spheres versus yellow spheres and panels. AB - Sticky red spheres can be used to capture western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), but red spheres have not been definitively shown to be more attractive than yellow traps. The objective of this study was to compare fly captures on ammonia-baited red spheres and yellow spheres and panels so that sensitive detection traps for fly management can be identified. Nontarget insects could interfere with fly captures, so weights of nontarget insects on traps were also determined. Yellow spheres and panels generally caught more flies than red spheres. More males than females were caught on nearly all red and yellow traps. Saffron Thread, Marigold, Sunny Summer, and Yam Yellow spheres and panels were bright yellow and generally caught more flies, especially females, than Cherry Cobbler Red or Tartar Red spheres. Twenty Carat Yellow and Glorious Gold spheres and panels were less bright and caught fewer flies than bright yellow traps and similar numbers of flies as Tartar Red spheres, respectively. Dry weights of nontarget insects on at least one yellow trap type were greater than on red spheres in only 4 of 10 tests. Results show that bright yellow spheres and panels capture more R. indifferens than red spheres and do not consistently capture greater amounts of nontarget insects than red spheres, suggesting that they should be used instead of red spheres for detecting this fly. PMID- 24224254 TI - Age-stage two-sex life tables of Panonychus ulmi (Acari: Tetranychidae), on different apple varieties. AB - To understand the influence of different apple varieties on the development and reproduction of the European red mite, Panonychus ulmi (Koch) (Acari: Tetranychidae), age-stage two-sex life tables of P. ulmi on 'Fuji,' 'Starkrimson Delicious,' 'Golden Delicious,' and 'Granny Smith' varieties were constructed under laboratory conditions at 23 +/- 1 degrees C, 75 +/- 5% relative humidity, and a photoperiod of 16:8 (L:D) h. Results showed that total development time of immature females was shorter on Fuji than on the other varieties, and this was because of its shorter egg duration. Immature survival of P. ulmi was 74.51 78.00% among four apple varieties, and no significant differences were found. The total fecundity per female was significantly higher on Golden Delicious (34.12 eggs per female) than that on Fuji (27.15 eggs per female), Starkrimson Delicious (25.15 eggs per female), and Granny Smith (20.62 eggs per female). Based on the intrinsic rate of population increase, Fuji and Golden Delicious were more suitable than Starkrimson Delicious and Granny Smith. PMID- 24224255 TI - Effects of spirotetramat on Aonidiella aurantii (Homoptera: Diaspididae) and its parasitoid, Aphytis melinus (Hymenoptera: Aphelinidae). AB - Laboratory and field studies were conducted to measure the effects of spirotetramat on life stages of California red scale, Aonidiella aurantii (Maskell), and a primary parasitoid, Aphytis melinus DeBach. Organophosphate resistant and -susceptible populations responded similarly to spirotetramat, suggesting there is no cross-resistance between these insecticide classes. First and second instar male and female A. aurantii were 10- and 32-fold more susceptible to spirotetramat (LC50 = 0.1-0.2 ppm) compared with early third (LC50 = 1.5 ppm) and late third instar females (LC50 = 5.3 ppm). The LC99 value indicated that late stage third instar females would not be fully controlled by a field rate of spirotetramat; however, spirotetramat would reduce their fecundity by 89%. Field applications of spirotetramat in two water volumes and using two adjuvants (oil and a nonionic spray adjuvant) showed similar reduction in A. aurantii numbers, even though the higher water volume demonstrated more complete coverage. These data suggest that this foliarly applied systemic insecticide can be applied in as little as 2,340 liters/ha of water volume, minimizing application costs, and that the two adjuvants acted similarly. The endoparasitoid, A. melinus, was unaffected by the field rate of spirotetramat when it was applied to the host when the parasitoid was in the egg or larval stage. Adult A. melinus showed 2 wk of moderate reductions in survival when exposed to leaves with field-weathered residues. Spirotetramat is an integrated pest management compatible insecticide, effective in reducing A. aurantii stages and allowing survival of its primary parasitoid A. melinus. PMID- 24224257 TI - Effect of climate change on annual fluctuations in the population density of the brown marmorated stink bug (Hemiptera: Pentatomidae) in northern Japan. AB - The relationship between the population density of overwintering adults of the brown marmorated stink bug and the temperatures of each month during the preceding November to April was investigated in Akita Prefecture, northern Japan, from 1999 to 2012. The number of adults entering traps for overwintering at the monitored hibernation site differed considerably among years. There was a significant negative correlation between the increase ratio (the ratio of the number collected in the current year to the number collected in the previous year) and the mean daily maximum temperature of the preceding March and April. These results suggest that the proportion of surviving adult brown marmorated stink bug may be higher when temperatures in early spring (March and April) are lower, as the postoverwintering adults may need to survive without food for a shorter period of time. PMID- 24224256 TI - Insecticide susceptibility of three species of cutworm (Lepidoptera: Noctuidae) pests of grapes. AB - Climbing cutworms in the genus Abagrotis are economically important pests of grapes in the Okanagan Valley of British Columbia (BC). Grapes are recently introduced into many areas of the region, and the association between crop and pest is new and still evolving. This has led to limited information being available on pest management strategies, including the evaluation of chemical controls compatible with local production practices. Few insecticides are currently registered in Canada for cutworm control on grapes, and our study was initiated to provide information on the efficacy of potential control materials. We were also interested in the relative susceptibilities of the three most common cutworm species attacking grape buds in BC--Abagrotis orbis (Grote), Abagrotis reedi Buckett, and Abagrotis nefascia (Smith). Dose-response bioassays with nine insecticides were conducted on neonate larvae using Bok Choy leaf disks, and on fourth-instar larvae using diet incorporation. There were considerable differences in the toxicity of insecticides within species for neonates and fourth instars. For some materials, the relative toxicity to neonates and fourth instars were not correlated. Response to insecticides among the three species showed variation as well, and correct identification of the species complex present in individual locations is important in choosing the best available control material. PMID- 24224258 TI - Separating the attractant from the toxicant improves attract-and-kill of codling moth (Lepidoptera: Tortricidae). AB - The behavior of codling moth, Cydia pomonella (L.), responding to three attract and-kill devices was compared in flight tunnel experiments measuring attraction and duration of target contact. Placing a 7.6 by 12.6 cm card immediately upwind of a rubber septum releasing pheromone, dramatically increased the duration on the target to > 60 s. In this setting, nearly all the males flew upwind, landed on the card first, and spent the majority of time searching the card. In contrast, male codling moths spent < 15 s at the source if given the lure only. In a forced contact bioassay, knockdown rate or mortality of male codling moths increased in direct proportion to duration of contact on a lambda-cyhalothrin loaded filter paper. When this insecticide-treated paper was placed immediately upwind of the lure in the flight tunnel, > 90% of males contacting the paper were knocked down 2 h after voluntary exposure. These findings suggest that past attempts to combine insecticide directly with sex pheromones into a small paste, gel, or other forms of dollops are ill-advised because moths are likely over exposed to pheromone and vacate the target before obtaining a lethal dose of insecticide. It is better to minimize direct contact with the concentrated pheromone while enticing males to extensively search insecticide-treated surface nearby the lure. PMID- 24224259 TI - Multi-state trials of Bt sweet corn varieties for control of the corn earworm (Lepidoptera: Noctuidae). AB - Field tests in 2010-2011 were performed in New York, Minnesota, Maryland, Ohio, and Georgia to compare Bt sweet corn lines expressing Cry1A.105 + Cry2Ab2 and Cry1Ab with their non-Bt isolines, with and without the use of foliar insecticides. The primary insect pest in all locations during the trial years was Heliocoverpa zea (Boddie), which is becoming the most serious insect pest of sweet corn in the United States. At harvest, the ears were measured for marketability according to fresh market and processing standards. For fresh market and processing, least squares regression showed significant effects of protein expression, state, and insecticide frequency. There was a significant effect of year for fresh market but not for processing. The model also showed significant effects of H. zea per ear by protein expression. Sweet corn containing two genes (Cry1A.105 + Cry2Ab2) and a single gene (Cry1Ab) provided high marketability, and both Bt varieties significantly outperformed the traditional non-Bt isolines in nearly all cases regardless of insecticide application frequency. For pest suppression of H. zea, plants expressing Bt proteins consistently performed better than non-Bt isoline plants, even those sprayed at conventional insecticide frequencies. Where comparisons in the same state were made between Cry1A.105 + Cry2Ab2 and Cry1Ab plants for fresh market, the product expressing Cry1A.105 + Cry2Ab2 provided better protection and resulted in less variability in control. Overall, these results indicate Cry1A.105 + Cry2Ab2 and Cry1Ab plants are suitable for fresh market and processing corn production across a diversity of growing regions and years. Our results demonstrate that Bt sweet corn has the potential to significantly reduce the use of conventional insecticides against lepidopteran pests and, in turn, reduce occupational and environmental risks that arise from intensive insecticide use. PMID- 24224260 TI - The influence of fipronil on Reticulitermes flavipes (Isoptera: Rhinotermitidae) feeding beyond treated plots. AB - A small-plot field trial was conducted to examine the area of influence of fipronil at incremental distances away from treated plots on the Harrison Experimental Forest near Saucier, MS. Small treated (water and fipronil) plots were surrounded by untreated wooden boards in an eight-point radial pattern, and examined for evidence of termite feeding every 60 d for 1 yr after treatment. Circular areas of 0, 0.28, 1.13, 2.55, 4.52, 7.07, and 10.18 m2 around the treated plots were installed to evaluate feeding damage by termites on the boards. The relationship between feeding damage to boards and area for each time interval was examined by using an exponential increase model. For both treatments and controls in nearly all periods examined, feeding was suppressed in the boards nearest to the treated plots, but increased exponentially as the area increased. Beginning 4 mo after treatment, treatment plots had lower proportions of boards with termite feeding evidence than control plots. Reduction in feeding was the only influence of fipronil observed beyond the treated plots. PMID- 24224261 TI - Detection of the A302S Rdl mutation in fipronil bait-selected strains of the German cockroach (Dictyoptera: Blattellidae). AB - Extensive usage and heavy reliance on insecticides have led to the development of insecticide resistance in the German cockroach, Blattella germanica (L.). Six field-collected strains of B. germanica from Singapore were used to investigate resistance to fipronil and dieldrin. The three strains (Boat Quay, Cavenagh Road, and Ghimmoh Road) with greatest resistance to fipronil were subjected to selection with fipronil bait up to the F5 generation. Synergism assay and molecular detection of a target site mutation were used to elucidate the mechanism of fipronil resistance in these strains. With the exception of the Cavenagh Road strain, all parental strains were susceptible to dieldrin. This strain exhibited resistance to dieldrin and fipronil with resistance ratios of 4.1 and 3.0, respectively. Piperonyl butoxide and S,S,S tributylphosphorotrithioate were antagonistic toward fipronil toxicity in all strains. Bait selection significantly increased fipronil and dieldrin resistance in the three chosen strains, either in topical bioassay or bait evaluations. There was a significant positive relationship [y = (6,852.69 +/- 1,988.37) x - (708.93 +/- 1,226.28), where x = fipronil toxicity and y = dieldrin toxicity] between dieldrin and fipronil resistance levels, indicating significant cross resistance between the insecticides. High frequencies of individuals possessing the Rdl gene mutation were found in the F5 generation of the three strains selected with fipronil bait. The synergism assays indicated that monooxygenase and esterase were not involved in fipronil resistance in the strains studied herein. The A302S Rdl mutation was the major mechanism contributing to fipronil and dieldrin resistance in these strains. PMID- 24224262 TI - Physiological and population responses of armyworm Mythimna separata (Lepidoptera: Noctuidae) to a sublethal dose of cantharidin-AC. AB - The oriental armyworm Mythimna separata Walker is a serious threat to the production of cereals. Its control has largely relied on synthetic insecticides, which led to the decrease in their effectiveness. In China, cantharidin, a natural compound of insect origin with a mode of action different from a conventional insecticide, is being developed as a bio-insecticide for the control of lepidopteran pests. Its toxicological effects have already been studied in M. separata. However, its sublethal effects on physiological and population parameters have not yet been studied. The leaf dip bioassay results showed that cantharidin-AC (cantharidin acetone solution) had a high level of toxicity against M. separata and the 96 h LC50 value was 223 microg/ml. The sublethal effects of cantharidin exposure for 72 h at LC10 (77 microg/ml) on physiological and population parameters of M. sepatata were also investigated, and data were subjected to an age-stage two-sex life-table. The sublethal effects of cantharidin indicated reduction in survival rates of larval, pupal, and adult stages. In addition, both male and female moths were observed with crippled wings in the cantharidin-treated cohort. The mean values of the finite rate of increase (lambda), the intrinsic rate of increase (gamma), and the net reproductive rate (R(o)) were significantly lower in the treatment than in the control. The fecundity was also strongly affected by a sublethal cantharidin concentration. A sublethal concentration of cantharidin may reduce the population growth of M. separata by decreasing its survival and reproduction and by increasing its generation time. PMID- 24224263 TI - Development of a methodology and evaluation of pesticides against Aceria litchii and its predator Phytoseius intermedius (Acari: Eriophyidae, Phytoseiidae). AB - The litchi erineum mite, Aceria litchii (Keifer), is the major pest of litchi, Litchi chinensis Sonnerat (Sapindaceae). This study evaluated the effect of 11 pesticides on the survival of A. litchii as well as on the survival and reproduction of Phytoseius intermedius Evans & McFarlane, the predator most found in association with it in Brazil. The containment of A. litchii in small petri dishes whose bottoms were covered with a solidified paste made of a mixture of gypsum and activated charcoal (9:1 in volume), kept humid, was shown to be adequate for this type of study. For the evaluation of the effect of pesticides on A. litchii, mites leaving the erinia from the pieces of litchi leaves (removed from the plants approximately 24 h earlier) were sprayed under a Potter tower and immediately transferred to the 2.5-cm-diameter petri dishes. After 2, 12, 24, and 48 h of the application, the dishes were examined to evaluate the mite survival. The four pesticides causing the highest levels A. litchii mortality, as well as azadirachtin, were tested for the effect on P. intermedius. For this test, experimental units consisted of discs of uninfested litchi leaves also sprayed under a Potter tower before introducing the predators. Survival and oviposition of the predator were evaluated every 24 h for 5 consecutive days; viability of the eggs laid was also evaluated. Highest mortality of A. litchii occurred with the application of fenpyroximate, sulfur, abamectin, and hexythiazox. Azadirachtin was considered moderately harmful to the predator P. intermedius, whereas other pesticides were classified as harmful. Despite the low efficiency of azadirachtin in the control of the pest, its relative selectivity to P. intermedius would encourage the evaluation on field condition, especially for use in organic production systems. PMID- 24224264 TI - Susceptibility baseline and chlorantraniliprole resistance monitoring in Chilo suppressalis (Lepidoptera: Pyralidae). AB - Chlorantraniliprole, a new anthranilic diamide insecticide, has been commercialized in China since 2008 for controlling of several lepidopterans, including rice stem borer, Chilo suppressalis Walker. Chemical control of this pest has become difficult because of its resistance development to many conventional insecticides. To facilitate chlorantraniliprole-resistance monitoring, seedling dip bioassays were conducted in 2011 and 2012 to assess the susceptibility of 30 populations of C. suppressalis from seven provinces in China. The assays established a larval susceptibility baseline with LC50 at 1.393 mg a.i/liter. The toxicity (LC50) of chlorantraniliprole against second-instar larvae of field populations ranged from 0.568 (SL12) to 13.547 (RA12) mg a.i/liter. Substantial variations of the susceptibility to chlorantraniliprole were detected among different geographic populations, but no significant difference was observed between years for most populations except for populations from Dong'an, Cangnan, and Lujiang. Resistance ratios to the chemical ranged from 1.0 to 9.7, indicating that most colonies remained susceptible or showed certain decrease in susceptibility. Approximately, 13.3% of the populations exhibited low levels of resistance to chlorantraniliprole. These data are useful in future monitoring program for detecting any changes in susceptibility as a result of use of the insecticide. PMID- 24224265 TI - Applying an integrated refuge to manage western corn rootworm (Coleoptera: Chrysomelidae): effects on survival, fitness, and selection pressure. AB - The refuge strategy can delay resistance of insect pests to transgenic maize producing toxins from Bacillus thuringiensis (Bt). This is important for the western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), because of its history of adaptation to several management practices. A 2-yr study across four locations was conducted to measure the effects of integrated refuge (i.e., blended refuge) on western corn rootworm survival to adulthood, fitness characteristics, and susceptibility to Bt maize in the subsequent generation. The treatments tested in this study were as follows: a pure stand of Bt maize (event DAS-59122-7, which produces Bt toxins Cry34Ab1/Cry35Ab1), a pure stand of refuge (non-Bt maize), and two variations on an integrated refuge consisting of 94.4% Bt maize and 5.6% non-Bt maize. Within the two integrated refuge treatments, refuge seeds received a neonicotinoid insecticidal seed treatment of either 1.25 mg clothianidin per kernel or 0.25 mg thiamethoxam per kernel. Insects in the pure stand refuge treatment had greater survival to adulthood and earlier emergence than in all other treatments. Although fecundity, longevity, and head capsule width were reduced in treatments containing Bt maize for some site by year combinations, Bt maize did not have a significant effect on these factors when testing data across all sites and years. We found no differences in susceptibility of larval progeny to Bt maize in bioassays using progeny of adults collected from the four treatments. PMID- 24224266 TI - Efficacies of spinosad and a combination of chlorpyrifos-methyl and deltamethrin against phosphine-resistant Rhyzopertha dominica (Coleoptera: Bostrichidae) and Tribolium castaneum (Coleoptera: Tenebrionidae) on wheat. AB - Highly phosphine-resistant populations of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) have recently been found in Oklahoma grain storage facilities. These findings necessitate development of a phosphine resistance management strategy to ensure continued effective use of phosphine. Therefore, we investigated the efficacies of two grain insecticides, namely, spinosad applied at label rate of 1 ppm and a mixture of chlorpyrifos-methyl and deltamethrin applied at label rates of 3 and 0.5 ppm, respectively, against highly phosphine-resistant R. dominica and T. castaneum. Adult mortality and progeny production suppression of spinosad- or chlorpyrifos-methyl + deltamethrin mixture-treated wheat that had been stored for 2, 84, 168, 252, and 336 d posttreatment were assessed. We found that both spinosad and chlorpyrifos-methyl + deltamethrin were effective against phosphine resistant R. dominica and caused 83-100% mortality and also caused total progeny production suppression for all storage periods. Spinosad was not effective against phosphine-resistant T. castaneum; the highest mortality observed was only 3% for all the storage periods. Chlorpyrifos-methyl + deltamethrin was effective against phosphine-resistant T. castaneum only in treated wheat stored for 2 and 84 d, where it caused 93-99% mortality. However, chlorpyrifos-methyl + deltamethrin was effective and achieved total suppression of progeny production in T. castaneum for all the storage periods. Spinosad was not as effective as chlorpyrifos-methyl + deltamethrin mixture at suppressing progeny production of phosphine-resistant T. castaneum. These two insecticides can be used in a phosphine resistance management strategy for R. dominica and T. castaneum in the United States. PMID- 24224268 TI - Population genetic structure of Pseudatomoscelis seriatus (Hemiptera: Miridae) in the cotton-growing regions of the United States. AB - The cotton fleahopper, Pseudatomoscelis seriatus (Reuter) (Hemiptera: Miridae) is an economically important insect pest of cotton in the United States. However, reports of cotton fleahopper infestation and its management in cotton fields are restricted primarily to Texas, Oklahoma, and Arkansas. The objective of this study was to understand the genetic diversity of cotton fleahopper populations infesting cotton in the cotton-growing areas of the United States. Amplified fragment length polymorphism markers were used to detect genetic diversity and to characterize geographic genotypes across the distribution of the cotton fleahopper in the United States. We used 172 individuals and 559 amplified fragment length polymorphism loci in this study and found significant, but low, level of genetic differentiation among geographic populations (F(ST) = 0.02; P < 0.0001). Molecular fingerprints of cotton fleahopper populations were partitioned into three broad regional genetic populations with a western, central, and eastern distribution. The western (Arizona) and eastern (Florida, Georgia, South Carolina, and North Carolina) populations are genetically distinct, whereas the central (Texas, Oklahoma, Arkansas, Mississippi, Louisiana, and Alabama) population represents an admixed population, which include both western and eastern populations. These results suggest considerable gene flow among the populations within regions but restricted gene flow among populations from eastern and western region. PMID- 24224267 TI - Colony breeding structure of the invasive termite Reticulitermes urbis (Isoptera: Rhinotermitidae). AB - Invasive species cause severe environmental and economic problems. The invasive success of social insects often appears to be related to their ability to adjust their social organization to new environments. To gain a better understanding of the biology of invasive termites, this study investigated the social organization of the subterranean termite, Reticulitermes urbis, analyzing the breeding structure and the number of reproductives within colonies from three introduced populations. By using eight microsatellite loci to determine the genetic structure, it was found that all the colonies from the three populations were headed by both primary reproductives (kings and queens) and secondary reproductives (neotenics) to form extended-family colonies. R. urbis appears to be the only Reticulitermes species with a social organization based solely on extended-families in both native and introduced populations, suggesting that there is no change in their social organization on introduction. F-statistics indicated that there were few neotenics within the colonies from urban areas, which did not agree with results from previous studies and field observations. This suggests that although several neotenics may be produced, only few become active reproductives. The results also imply that the invasive success of R. urbis may be based on different reproductive strategies in urban and semiurbanized areas. The factors influencing an individual to differentiate into a neotenic in Reticulitermes species are discussed. PMID- 24224269 TI - Feeding behavior comparison of soybean aphid (Hemiptera: Aphididae) biotypes on different soybean genotypes. AB - Soybean aphids have become a serious pest of soybean, Glycine max L. (Merrill), since they were first detected in North America in 2000. Three soybean aphid biotypes have been documented in the United States in the last 10 yr, but few studies have been done on their feeding behavior in the United States The Electrical Penetration Graph is a convenient and successful tool to study the feeding behavior of piercing and sucking insects. This is the first attempt to study the feeding behavior differences between biotype 1 and biotype 2 on soybean genotypes using the Electrical Penetration Graph technique, and includes both resistant and susceptible soybean genotypes from Kansas and Michigan. The experiments were run for 9 h each for each genotype with a total of eight channels at a time. Results indicated that aphids feeding on susceptible genotypes had a significantly greater duration of sieve element phase than when feeding on resistant genotypes. Furthermore, the time taken to reach the first sieve element phase in resistant genotypes was significantly greater than in susceptible genotypes. Most of the aphids reached sieve element phase (> 90%) in susceptible genotypes, but only a few (< 30%) reached sieve element phase in resistant genotypes during the 9-h recording period; however, we found no differences in any other probing phases between resistant and susceptible genotypes except the number of potential drops in biotype 2. Thus, the resistance was largely associated with phloem tissues. Therefore, some biochemical, physical, or morphological factors could affect stylet penetration of aphids. PMID- 24224270 TI - Is it possible to control fumonisin contamination in maize kernels by using genotypes resistant to the Mediterranean corn borer? AB - Insect activity has long been associated with Fusarium infection. The objectives of the current study were 1) to estimate the impact of Mediterranean corn borer, Sesamia nonagrioides Lefebvre, damage on fumonisin contamination in the maize kernel by comparing fumonisin contamination under infestation and protected conditions, and 2) to measure the potential use of genotypes resistant to this borer as controlling factors of fumonisin contamination. Genotypes with increased kernel damage by borers tended to increase fumonisin accumulation under infestation conditions. In particular environments, other factors influenced fumonisin contamination more than damage by borers. When ear damage by borers is significant, maize resistance to ear damage could contribute to the reduction of fumonisin contamination in the kernels. Genotype such as EP42 x EP77 that combines low ear damage by borers and low fumonisin level across environments is a good choice to control fumonisin contamination. The use of an applicable methodology to identify Mediterranean corn borer-resistant genotypes to ear attack under artificial infestations might be a promising approach. PMID- 24224271 TI - Models to predict mortality of Tribolium castaneum (Coleoptera: Tenebrionidae) exposed to elevated temperatures during structural heat treatments. AB - Novel thermal death models were developed with certain assumptions, and these models were validated by using actual heat treatment data collected under laboratory conditions at constant temperatures over time and in commercial food processing facilities where temperatures were dynamically changing over time. The predicted mortalities of both young larvae and adults of the red flour beetle, Tribolium castaneum (Herbst), were within 92-99% of actual measured insect mortalities. There was good concordance between predicted and observed mortalities of young larvae and adults of T. castaneum exposed to constant temperatures in laboratory growth chambers and at variable temperatures during structural heat treatments of commercial food-processing facilities. The models developed in this study can be used to determine effectiveness of structural heat treatments in killing young larvae and adults of T. castaneum and for characterizing insect thermotolerance. PMID- 24224272 TI - Do phosphine resistance genes influence movement and dispersal under starvation? AB - Phosphine resistance alleles might be expected to negatively affect energy demanding activities such as walking and flying, because of the inverse relationship between phosphine resistance and respiration. We used an activity monitoring system to quantify walking of Rhyzopertha dominica (F.) and a flight chamber to estimate their propensity for flight initiation. No significant difference in the duration of walking was observed between the strongly resistant, weakly resistant, and susceptible strains of R. dominica we tested, and females walked significantly more than males regardless of genotype. The walking activity monitor revealed no pattern of movement across the day and no particular time of peak activity despite reports of peak activity of R. dominica and Tribolium castaneum (Herbst) under field conditions during dawn and dusk. Flight initiation was significantly higher for all strains at 28 degrees C and 55% relative humidity than at 25, 30, 32, and 35 degrees C in the first 24 h of placing beetles in the flight chamber. Food deprivation and genotype had no significant effect on flight initiation. Our results suggest that known resistance alleles in R. dominica do not affect insect mobility and should therefore not inhibit the dispersal of resistant insects in the field. PMID- 24224273 TI - Health information management: what a ride it has been. PMID- 24224274 TI - Ticking time clock--or bomb? PMID- 24224275 TI - Analytics assemble. PMID- 24224276 TI - The weight of the I.T. evidence. PMID- 24224277 TI - Building Leaders. Interview by Elizabeth Gardner. PMID- 24224278 TI - Known knowns, known unknowns and unknown unknowns: the science and the passion of HBO2 therapy and traumatic brain injury: an editorial perspective. PMID- 24224279 TI - Publication rates for Annual Scientific Meeting abstracts: a cause for concern? An editorial perspective. PMID- 24224280 TI - Effect of hyperbaric oxygen on the growth and development of medicinal maggots. AB - Some wound care therapists use both maggot debridement therapy (MDT) and hyperbaric oxygen (HBO2) therapy to treat non-healing wounds. Some practitioners have reported success using both MDT and HBO2 therapy concurrently; others have not. To begin evaluating the utility of using MDT and HBO2 therapy concurrently, we assessed the effects of hyperbaric oxygen (HBO2) on maggot growth and development, as a surrogate for debridement capacity. Replicate sets of medical grade blowfly larvae were placed on liver-agar wound models and exposed to HBO2 at 2.0 atmospheres absolute (atm abs) for 90 minutes on 0 (control), 1, 2 or 3 sequential days. The effects of HBO2 exposure were quantified by measuring the maggots' subsequent growth and development. Exposure to HBO2 was most lethal to young larvae (second instars), but not to older larvae (third instars). There was no dose-relationship between the number of HBO2 treatments and rate of larval survival. Our findings suggest that maggot therapy and HBO2 therapy may be administered concurrently, as long as the larvae are not too immature (that is, as long as they are beyond the second instar) by the time they take their first dive. A clinical trial evaluating the clinical benefits of concurrent HBO2 therapy and MDT is warranted. PMID- 24224281 TI - The effect of hyperbaric oxygen therapy on treatment of wound complications after oral, pharyngeal and laryngeal salvage surgery. AB - INTRODUCTION: Radiation therapy alone, or combined with chemotherapy, are both used for cancer in the head and neck. This can lead to damage of tissue cells and vasculature. Surgery in such compromised tissues has increased complication rates, because wound healing with angiogenesis and fibroplasias requires normal cell growth conditions. Hyperbaric oxygen therapy raises oxygen levels in hypoxic tissue, stimulates angiogenesis and fibroplasia. In this report, we review the clinical value of hyperbaric oxygen therapy for major wounds that had shown no signs of healing as well as fistulas after salvage surgery in patients treated with (chemo)radiation of the head and neck regions. METHODS: In this retrospective study, 16 patients with soft-tissue wounds without signs of healing after salvage surgery, after radiation, and most after chemotherapy were treated in the head and neck regions with hyperbaric oxygen therapy. The patients were treated by HBO2, 2.5 bars 90 minutes daily, usually 20 treatments. RESULTS: The healing processes seemed to be initiated and accelerated by HBO2. Fourteen of the 16 patients healed completely. There were no life-threatening complications. CONCLUSION: Radiotherapy and combined chemoradiation therapy leads to damage of tissue cells and vasculature. Salvage surgery in such tissues has an increased complications rate, because wound healing requires angiogenesis and fibroplasias, all of which are jeopardized. Hyperbaric oxygen therapy raises oxygen levels in hypoxic tissue, stimulates angiogenesis and fibroplasias and is an effective and powerful treatment for postoperative wounds in oral, pharyngeal and laryngeal carcinomas surgery. PMID- 24224282 TI - Fate of abstracts presented at the annual scientific meeting of the Undersea and Hyperbaric Medical Society. AB - INTRODUCTION: The full-text publication of abstracts presented at any given scientific meeting in peer-reviewed journals is accepted as a measure of scientific quality of that particular meeting. The aim of this study is to determine the full-text publication rate of abstracts presented at the 2005 Scientific Meeting of the Undersea and Hyperbaric Medical Society (UHMS). METHODS: We identified the scientific abstracts presented at the 2005 UHMS meeting and searched the PubMed database (June 2005 to July 2010) for their corresponding full-text publication. We recorded the following parameters for each of the abstracts: number of authors, number of centers involved in the study, statistical methods used, country of origin of the study, study type, and subject of the abstract. We recorded the time to publication and the title of the journal if the abstract had been published in a peer-reviewed journal. RESULTS: Overall, we identified 187 abstracts presented at the 2005 UHMS meeting. Two of the abstracts were excluded from the study because they had been retracted from the meeting and six more because they had been already published as full-text articles at the time the meeting was held. Of the 179 abstracts, 62 (34.6%) were published as full-text articles within the succeeding five years. The mean (+/- SD) time to publication was 18.5 (+/- 13.6) months. Multivariate analysis with logistic regression identified "country of origin" and "the subject of the abstract" as independent predictors of full-text publication. CONCLUSION: We found that only one-third of the abstracts presented at the 2005 UHMS meeting were published as full-text articles within the succeeding five years. Although this rate is consistent with similar studies from various disciplines, further research is needed to identify the specific barriers to full-text publication of abstracts in the field of underwater and hyperbaric medicine. PMID- 24224283 TI - Chamber personnel's use of Nitrox 50 during hyperbaric oxygen treatment: a quality study--research report. AB - OBJECTIVE: We aimed to evaluate the feasibility and safety of using Nitrox 50 as breathing gas during attendance in a multiplace hyperbaric chamber. METHODS: Paper logs between Jan.-Dec. 2011 were reviewed to analyze nitrogen gas-loading, actual bottom time, total bottom time and surface interval time. With the use of the Norwegian Diving Tables nitrogen gas-loading was converted to Repetitive Group Letters. Symptoms of decompression sickness and health problems related to hyperbaric exposures were registered at weekly staff meetings. The chamber personnel breathed chamber air or Nitrox 50. RESULTS: 1,207 hyperbaric exposures were distributed to five chamber attendants and technicians, 14 doctors, and six nurses. Nitrox 50 was inhaled on 978 occasions (81.0%). Median nitrogen gas loading after first pressurization complied with Repetitive Group Letter A (range A-E), second to C (range A-F), third to D (range A-F), fourth to E (range C-H), fifth to F (range C-H), and sixth to E (range B-G). No symptoms of decompression sickness were reported (95% CI 0.00-0.33%). CONCLUSION: Breathing Nitrox 50 during repetitive hyperbaric sessions seems to be feasible and safe while meeting high demands in number of treatment sessions and patient flow and with fewer people employed in the hyperbaric unit. PMID- 24224284 TI - Negative pressure breathing increases cardiac output and nitrogen elimination in seated subjects. AB - During denitrogenation for rescue, crew members of an internally pressurized disabled submarine (DISSUB) must sit upright, which may hamper venous return, cardiac output and peripheral circulation. Since negative pressure breathing (NPB) might counteract this problem, denitrogenation was measured in sitting subjects performing NPB. Seven male subjects completed 125-minute nitrogen (N2) washouts breathing either 100% oxygen (O2) or a normoxic gas (21% O2 in argon) in control conditions and intermittent (I: inspirations only) or continuous (C) NPB at -10 or -15 cmH2O. N2 elimination was measured using a closed rebreathing system. INPB (intermittent) (-15cmH2O) and CNPB (continous breathing) (-10 and 15cmH2O) increased cardiac output (CO) 9% during both O2 and normoxic breathing. Systolic and diastolic blood pressures were unaffected by the CO increase, suggesting a peripheral vasodilatation and enhanced tissue perfusion leading to increased N2 elimination. With the CO boost, N2 washout increased 6% breathing O2 at -15 cmH2O CNPB and INPB, while during normoxic breathing there were 6% and 12% increases due to CNBP, -10 and -15 respectively and 6% with -15cmH2O INPB; breathing 100% O2 yielding 5% to 15% less N2 washout than normoxic breathing. Negative pressure breathing during denitrogenation may facilitate decompression in divers and in crew members being rescued from a DISSUB. PMID- 24224285 TI - Swimming-induced immersion pulmonary edema while snorkeling can be rapidly life threatening: case reports. AB - It is well known that immersion pulmonary edema can be life-threatening for divers using a self-contained underwater breathing apparatus (scuba). Swimming induced pulmonary edema in otherwise healthy individuals is not an object of dispute but its real severity is not well known and is probably underestimated. We report two cases of life-threatening acute respiratory distress while swimming and snorkeling, one of which is well documented for swimming-induced pulmonary edema. The interest of these case reports lies in the suddenness of these life threatening events. Such accidents can mimic a loss of consciousness due to cardiac dysrhythmia and lead to drowning. In the case of swimming-induced pulmonary edema, the prognosis is far better than for a cardiac disorder, but it is also dependent on the efficiency of the supervision. Swimmers, divers, race organizers and supervising physicians should be given knowledge of this pathology and its potentially acute occurrence. Adequate organizational dispositions are mandatory to prevent swimming-induced pulmonary edema-related deaths. PMID- 24224286 TI - Randomized controlled trials in diving and hyperbaric medicine. AB - Randomized controlled trials (RCTs) are widely accepted as the most appropriate methodology available for the investigation of health interventions. This is because of the low potential for systematic bias and the ability to assume causality. Well-designed RCTs, often modified by the addition of blinding participants to the treatment allocated, greatly assist physicians and funding agencies in deciding on the most effective and cost-efficient methods available to prevent and treat ill health. One of the problems for hyperbaric physicians is the widely scattered nature of the evidence, making retrieval and appraisal problematic. This review assembles the randomized evidence in order to assist practitioners, discusses the nature of randomized trials and explores approaches to designing and performing powerful and convincing trials in this area. It is extracted from the UHMS Report Hyperbaric Oxygen Therapy Indications. PMID- 24224287 TI - Regulatory considerations for a traumatic brain injury (TBI) indication for hyperbaric oxygen (HBO2). PMID- 24224288 TI - Hyperbaric oxygen (HBO2) for post-concussive syndrome/chronic TBI--product summary. PMID- 24224289 TI - Department of Defense trials for hyperbaric oxygen and TBI: issues of study design and questionable conclusions. PMID- 24224290 TI - Reply: Department of Defense trials for hyperbaric oxygen and TBI: issues of study design and questionable conclusions. PMID- 24224291 TI - Prolongation of latency is not enough in prevention of central nervous system oxygen toxicity. PMID- 24224292 TI - Diagnosis and treatment of endoleaks after endovascular repair of thoracic and abdominal aortic aneurysms. AB - A common complication of endovascular repair of a thoracic or abdominal aortic aneurysm (TEVAR - EVAR) is an endoleak occurring in up to 30% of cases. Endoleak is defined as the persistence of blood flow outside the lumen of the endoprosthesis, but within the aneurysm sac and can be classified into 5 categories, depending on the blood flow into the aneurysm sac. Typical features of the different types of endoleaks are discussed as well as the imaging modalities to detect and classify an endoleak and the diverse (endovascular) treatment options. PMID- 24224293 TI - Feasibility of an optimized MR enterography protocol in the evaluation of pediatric inflammatory bowel disease. AB - Cross-sectional imaging forms an important alternative and complimentary tool to endoscopy in aiding the clinician with diagnosis and management of pediatric inflammatory bowel disease (IBD). The purpose of the study was to evaluate the feasibility of an optimized Magnetic Resonance Enterography (MRE) protocol in the evaluation of patients with suspected IBD. 31 children (18 boys and 13 girls) were evaluated by a pediatric gastroenterologist prior to MRE and given a grading for clinical severity of disease. Imaging was then performed with oral contrast and a tailored protocol using fast T1/T2 weighted pulse sequences. Additionally, contrast and glucagon were administered intravenously. Imaging findings were then correlated with the clinical data. Excellent distension was achieved in the small bowel. The majority of the studies were of diagnostic quality with no motion artifacts. Imaging findings showed statistically significant correlation with disease activity. An optimized pediatric MRE protocol is feasible and correlates well with clinical disease activity. This in turn aids the clinician in the management of children with this chronic debilitating disease. PMID- 24224294 TI - Demographic changes in brain CT and MR imaging between 1990 and 2010. AB - STUDY OBJECTIVE: During the last decades, computed tomography and magnetic resonance imaging have revolutionized neuro-imaging. Nowadays these techniques are routinely used, but the extent and variation of use has been investigated poorly. Our purposes were to retrospectively determine the evolution in demographic variables and indications of cranial CT and MRI scanning in 1993, 2000 and 2009, at our hospital. METHODS: We retrospectively studied medical and neurologic in- and outpatients, who underwent CT- or MR imaging of the head for several demographic and patient characteristics. RESULTS: We observed a modest increase in mean age and a marked increase in total number of cranial CT examinations, MR confirmation studies and repeat examinations. Metastatic disease, head injury and headache were indications associated with more rapid growth in CT use than were others. CONCLUSION: Among the 5 patient and hospital factors considered (total number of examinations, age, indication, MR confirmation study and repeat examinations), all had a significant variation during the past 16 years. Strict regulations with compelling guidelines for the rational use of brain CT and MRI are inevitable in order to control expenditure and radiation exposure. PMID- 24224295 TI - Intralobular pulmonary sequestration. PMID- 24224296 TI - Perforation of the urinary bladder wall by Foley catheter. PMID- 24224297 TI - Benign lipoma of the inferior vena cava. PMID- 24224298 TI - Congenital hemangioma of the skull. PMID- 24224299 TI - Goblet cell carcinoid tumor of the appendix. PMID- 24224300 TI - Bilateral branchial cleft fistula. PMID- 24224301 TI - Hepar lobatum carcinomatosum. PMID- 24224302 TI - Subacute intramural hematoma of the aorta. PMID- 24224303 TI - Parathyroid carcinoma. PMID- 24224304 TI - Lyme neuroborreliosis. PMID- 24224305 TI - Multifocal nodular steatosis. PMID- 24224306 TI - Osteoid osteoma. PMID- 24224307 TI - Superior vena cava syndrome caused by Behcet's disease. PMID- 24224308 TI - Spontaneous splenic rupture in infectious mononucleosis. PMID- 24224309 TI - Bizarre parosteal osteochondromatous proliferations of the fingers. PMID- 24224310 TI - Chondroblastoma of calcaneus. PMID- 24224311 TI - Avulsion fracture of the anterior inferior iliac spine. PMID- 24224312 TI - Aortic coarctation. PMID- 24224313 TI - Gallstone ileus with a biliodigestive fistula. PMID- 24224314 TI - Polyostotic fibrous dysplasia. PMID- 24224315 TI - Small bowel diverticulosis. PMID- 24224316 TI - Rotator interval lesion. PMID- 24224317 TI - Intraosseous dissecting ganglion of the knee. PMID- 24224318 TI - Lipoma arborescens. PMID- 24224319 TI - Yolk sac tumor of the ovary. PMID- 24224320 TI - Neonatal cephalohematoma. PMID- 24224321 TI - Orbital dermoid. PMID- 24224322 TI - Large occipital nerve (Arnold's nerve) schwannoma. PMID- 24224323 TI - Sprengel's shoulder. PMID- 24224324 TI - Giant hydronephrosis in a 42-year-old man revealed by low back pain. PMID- 24224325 TI - Unusual cause of pelvis pain and polyuria in an adolescent: idiopathic megarectum. PMID- 24224326 TI - Paradoxical reaction in non HIV-tuberculosis, a rare case with pancreatic involvement. PMID- 24224327 TI - Atypical obstructive submandibular sialoadenitis. PMID- 24224328 TI - Bilateral selective amygdala calcifications: lipoid proteinosis. PMID- 24224329 TI - Shopping for whole grains: an aisle-by-aisle guide. PMID- 24224330 TI - Cooking 101: Low-fat cooking. PMID- 24224331 TI - Kidney disease: dietary restrictions for prevention and treatment. PMID- 24224332 TI - Diabetes quiz. How much do you know about the HbA1c test? PMID- 24224333 TI - Everything you ever wanted to know about injecting insulin...but didn't know to ask. PMID- 24224334 TI - Recipe makeovers. Banana nut bread. PMID- 24224335 TI - Supermarket smarts. meat substitutes. PMID- 24224336 TI - Crowded plates: for CIOs, policy mandates are piling up. Just how many policy issues are healthcare IT leaders facing? PMID- 24224337 TI - Life after the Beacon. San Diego Beacon transitions into a regional HIE organization. PMID- 24224338 TI - A framework to aid VNA implementation. VNAs are an effective way to address the clinical content that is growing in importance as EMRs evolve as part of meaningful use. PMID- 24224339 TI - Shining a light on patient engagement. How one hospital places the tools for engagement in the hands of the patients. PMID- 24224340 TI - Why the idea of a patient portal sells itself. A patient portal that meets patients' expectations of convenience, accuracy, and communication for their healthcare. Interview by Gabriel Perna. PMID- 24224341 TI - A physician-first approach to clinical documentation improvement. A regional health system's CDI initiative enlists physicians while meeting institutional and cultural needs. PMID- 24224342 TI - Helping consumers navigate claims data. An initiative aims for transparency in healthcare costs. PMID- 24224343 TI - Digital health center at UCSF clears the path for innovation. The new initiative aims to drive precision medicine forward. Interview by Rajiv Leventhal. PMID- 24224344 TI - The value of back-channel references. How to use 'back channel' contacts to shed light on job candidates. PMID- 24224345 TI - Set up to succeed. AB - You've found the new CEO; onboarding will help you keep her. PMID- 24224346 TI - In a value-based world physician alignment is the path to success. AB - Building closer, more supportive relationships with physicians is the only way to thrive in a value-based world. PMID- 24224347 TI - Competitors as collaborators. AB - Driven by a shared mission, former rivals are forming unlikely partnerships to meet community needs. PMID- 24224348 TI - 2014 Environmental Scan. PMID- 24224349 TI - Fresh insights at the table. AB - Younger trustees can bring valuable new perspectives to boards. To recruit them, start streamlining meetings. PMID- 24224350 TI - Value moves to the forefront. AB - Accountable care is changing how boards protect their hospitals' continued viability. PMID- 24224351 TI - A call to eliminate disparities. AB - A national partnership pushes equity and diversity. PMID- 24224352 TI - No longer the sole provider. AB - A Texas system connects with local partners to expand services. PMID- 24224353 TI - Preying on the pancreas? Scientists debate whether newer diabetes medications do harm. PMID- 24224354 TI - Sick-day rules: What to do when you are feeling under the weather. PMID- 24224355 TI - Doing right in Durham: Medical professionals and residents saw needs in their North Carolina community--and they're taking steps to fill them. PMID- 24224356 TI - Shopping for insurance: Marketplaces are a new way to find health care coverage. PMID- 24224357 TI - Lil Jon's big effort: Why the rap superstar raised $160,000 for the American Diabetes Association. PMID- 24224358 TI - 'We make the difference': Geisinger Medical Center's ES team lives its motto. PMID- 24224359 TI - 'Extraordinary people. Exceptional care': Blanchard Valley Hospital ES team goes the extra mile. PMID- 24224360 TI - Cost-effective design: Saving money by selecting the right finishes. PMID- 24224361 TI - Calming influence: Redesigning hospital spaces for palliative care. PMID- 24224362 TI - Game-changing opportunities in waste recycling. PMID- 24224363 TI - Going for the green: Tools to help hospitals on the road to sustainability. PMID- 24224364 TI - Favorable response: Nurse call systems evolve to boost patient satisfaction. PMID- 24224365 TI - [What is your diagnosis? Deglutition disorder, spots on hands and gums]. PMID- 24224366 TI - [These accounting items are new]. PMID- 24224367 TI - [New guidelines for chronic constipation: relief is urgently sought]. PMID- 24224368 TI - [Physical protection: stockings as standard in thrombosis prevention]. PMID- 24224369 TI - [Secondary prevention: is arteriosclerosis already an illness?]. PMID- 24224370 TI - [Risk for every tenth survivor: after cancer is before cancer]. PMID- 24224371 TI - [Growth sector psychiatry]. PMID- 24224372 TI - [Factitious disorders: doctors be aware]. PMID- 24224373 TI - [To identify and treat obsessive-compulsive disorders: an overview]. PMID- 24224374 TI - [Smoking cessation]. PMID- 24224375 TI - [Radiating pain: disc herniation is a rare cause only]. PMID- 24224376 TI - [Diabetes and skin]. PMID- 24224377 TI - [Prevention and therapy of thromboembolism: rivaroxaban - better outcome - risk profile as standard therapy]. PMID- 24224378 TI - [Phytotherapy instead of multiple medications: multimodal effect against cough and bronchitis]. PMID- 24224379 TI - Editorial policy of the Japanese Journal of Toxicology (Semiofficial journal of the Japanese Association of Clinical Toxicology). PMID- 24224380 TI - [Diagnosis and treatment of snakebite by Mamushi and Yamakagashi]. PMID- 24224381 TI - [Basics of mushroom poisoning: statistics and identification mushroom poisoning in Japan]. PMID- 24224382 TI - [Species identification of mushrooms using molecular data]. PMID- 24224383 TI - [Clinical toxicology of mushroom poisoning. Amanita virosa]. PMID- 24224384 TI - [Clinical toxicology of mushroom poisoning. Omphalotus guepiniformis]. PMID- 24224385 TI - [Clinical toxicology of mushroom poisoning. Amanita pantherina, Amanita ibotengutake]. PMID- 24224386 TI - [Clinical toxicology of mushroom poisoning. Clitocybe clavipes, Coprinopsis atramentarius]. PMID- 24224387 TI - [Survey of analytical works for drugs at emergency and critical care centers with high-performance instruments provided by the Ministry of Health and Welfare (at present: Ministry of Health, Labour, and Welfare) in fiscal 1998--continuation of survey with 2008 survey results as point of reference]. AB - In a 2008 survey of the 73 emergency and critical care centers around the nation that were equipped with the drug and chemical analytical instrument provided by the Ministry of Welfare (currently the Ministry of Health, Labour, and Welfare) in 1998, 36 of those facilities were using the analytical instruments. Of these 36 facilities, a follow-up survey of the 17 facilities that recorded 50 or analyses per year. Responses were gained from 16 of the facilities and we learned that of those, 14 facilities (87.5%) were conducting analyses using the instrument. There was a positive mutual correlation between the annual number of cases of the 14 facilities conducting analyses with the instrument and the number of work hours. Depending on the instrument in use, average analytical instrument parts and maintenance expenses were roughly three million yen and consumables required a maximum three million yen for analysis of 51-200 cases per year. From this, we calculate that such expenses can be covered under the allowed budget for advanced emergency and critical care centers of 5,000 NHI points (1 point = 10 yen). We found there were few facilities using the instrument for all 15 of the toxic substances recommended for testing by the Japanese Society for Clinical Toxicology. There tended to be no use of the analytical instrument for compounds with no toxicology cases. However, flexible responses were noted at each facility in relation to frequently analyzed compounds. It is thought that a reevaluation of compounds subject to analysis is required. PMID- 24224388 TI - Case of multiple organ failure due to benzine ingestion. AB - A 42-year-old woman was admitted to our ICU for acute respiratory failure due to benzine ingestion. On arrival at the hospital, the patient's consciousness level was GCS 3 and her SpO2 was 89% when receiving oxygen at 10 L/min. She was immediately intubated and placed on a ventilator. Chest X-ray and CT scanning showed a wide infiltrative pulmonary shadow bilaterally, and a diagnosis of acute respiratory distress syndrome (ARDS) was made. Subsequently, she became anuric and required haemodiafiltration on the 2nd day. Complications such as prolonged circulatory failure, liver dysfunction and disseminated intravascular coagulation (DIC) were then observed, and plasma exchange therapy was initiated. The patient's condition improved and a complete recovery ensued. The patient remained suicidal and was moved to the psychiatric ward for psychiatric support. Benzine is purified oil containing aliphatic hydrocarbons and is liquid at room temperature. In this case, the patient had already ARDS that required immediate intubation on arrival at the hospital. On this basis, aspiration of benzine into the lungs was considered to have occurred concomitantly with its ingestion, which therefore led to the complication of chemical pneumonitis in addition to that of circulatory shock, acute kidney injury, liver dysfunction and DIC. PMID- 24224389 TI - [Case of dyspnea due to toilet cleaner containing nitric acid for household use]. AB - A 40-year-old male tried to clean a urinal at his home storing 900 mL of a toilet cleaner containing 9.8% nitric acid to remove calcium deposit, and clean the toilet floor for twenty minutes. Immediately after using the cleaner, he experienced eye irritation. He washed out the toilet cleaner. However, he thereafter experienced dyspnea, a compressive sensation in his chest, and chest and back pain about 40 minutes after the cleaning the toilet. He monitored his symptoms overnight and found them to gradually improve. However, the symptoms still remained the next morning and therefore he came to our department on foot. He had no particular past or family history. On arrival, his physiological findings and chest computed tomography scan were negative for any abnormalities. His arterial blood gas analysis revealed a mild abnormality of oxygenation. Observation without any drugs revealed that a complete remission of his symptoms occurred after approximately 4 weeks. Based on the results of the experiments, contact with the mucosal membrane and nitric acid gas produced by any accidentally coexisting metals or contact with moisture, including nitric acid produced by a reaction between CaCO3 and cleaner, may have been the mechanism of occurrence for the symptoms observed in this case. This is the first reported case of nitric acid poisoning due to the use of a toilet cleanser intended for household use. PMID- 24224390 TI - [Acute poisoning of droxidopa: report of a case]. PMID- 24224391 TI - [Practical analysis of toxic substances useful for clinical toxicology. (3) Detection methods of cathinone compounds]. PMID- 24224392 TI - [Multicenter retrospective survey on a suicide trend using hydrogen sulfide]. PMID- 24224393 TI - [Iron (III) hexacyanoferrate (II) hydrate Prussian blue insoluble)]. PMID- 24224394 TI - [Investigation of acute aconite poisoning received in Japan Poison Information Center]. PMID- 24224395 TI - Prospective evaluation of office-based injection laryngoplasty with hyaluronic acid gel. AB - OBJECTIVES: The role of Juvederm Ultra Plus hyaluronic acid gel for use in injection laryngoplasty has not been well examined. The aim of this study was to prospectively assess the safety and clinical effectiveness of office-based injection laryngoplasty of Juvederm Ultra Plus gel in patients with glottic insufficiency. METHODS: Thirty patients met the criteria for study inclusion and were treated with unsedated office-based injection laryngoplasty of Juvederm Ultra Plus gel over a 20-month period. The preinjection acoustic and aerodynamic measures, Voice Handicap Index, Glottal Function Index, and Dysphonia Severity Index were compared with values recorded at 1 and 4 months after injection. RESULTS: Data for 27 patients were available for follow-up analysis at 1 month, and 12 patients' data were available at 4 months. Significant improvements, compared to preinjection levels (p < 0.02), were shown in all outcome measures at 1 and 4 months. One patient required intravenous steroid therapy for delayed glottic inflammation that resolved without permanent sequelae. CONCLUSIONS: The injection of Juvederm Ultra Plus gel is a relatively safe procedure that allows for short-term improvements in objective and subjective outcome measures of vocal function in patients with glottic insufficiency, provided the surgeon remains alert to the possibility of postprocedural injection site inflammation. PMID- 24224396 TI - Carbon dioxide laser fiber for the excision of oral leukoplakia. AB - OBJECTIVES: We compared the efficacies of cold knife excision and carbon dioxide (CO2) laser fiber excision of oral cavity leukoplakia. METHODS: Between August 2009 and June 2011,45 patients who underwent excision of oral cavity leukoplakia were assessed for operative time, use of bipolar cautery, blood loss, and number of intraoperative margins needed. Patients were assigned randomly to either a cold knife group (23 procedures) or a CO2 laser fiber group (24 procedures) at the time of the procedure. RESULTS: The times of excision were similar in the CO2 laser fiber group (1.64 min/cm2) and the cold knife group (1.70 min/cm2). There were large differences between the CO2 laser fiber group and the cold knife group in the categories of bipolar cautery uses per square centimeter (0.34 uses versus 3.32 uses) and blood loss (0.19 g/cm2 versus 2.55 g/cm2). The average number of margins needed to clear a specimen by frozen section was 1.21 for the CO2 laser fiber group and 1.83 for the cold knife group. CONCLUSIONS: The CO2 laser fiber did not show an advantage in operative time. The CO2 laser fiber did show better outcomes in the areas of blood loss, bipolar cautery use, and intraoperative margins needed. PMID- 24224397 TI - Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas. AB - OBJECTIVES: We sought to determine the effect of propranolol on cardiovascular and blood glucose parameters in infants with symptomatic infantile hemangiomas who were hospitalized for initiation of treatment, and to analyze adverse effects of propranolol throughout the course of inpatient and outpatient treatment. METHODS: A retrospective cohort analysis was performed on 50 infants (age less than 12 months) with symptomatic infantile hemangiomas who were hospitalized for propranolol initiation between 2008 and 2012. Demographic data and disease characteristics were recorded. Systolic and diastolic blood pressures, heart rate, blood glucose values, and adverse events recorded during hospitalization were analyzed. An additional cohort of 200 consecutively treated children was also assessed for adverse events associated with outpatient propranolol use. RESULTS: The median age among the inpatient cohort was 3.4 months (range, 0.8 to 12.0 months). Infants older than 6 months were more likely to exhibit bradycardia than were younger infants (p < 0.001). Hypotensive and/or bradycardic periods were infrequent and were not associated with observable clinical symptoms. The mean systolic and diastolic blood pressures and the mean heart rate decreased significantly from day 1 of hospitalization to day 2 (p = 0.004; p = 0.008; p < 0.001), but not from day 2 to day 3, when the propranolol dose was increased to target. Hypoglycemia was rare (0.3% incidence.) Among the 250 outpatients, 2 infants developed lethargy and hypoglycemia during a viral illness and recovered without sequelae. One infant experienced recurrent bronchospasm with viral illnesses and required concomitant bronchodilator therapy. CONCLUSIONS: Frequent deviations from normal ranges of blood pressure and heart rate occur upon initiation of propranolol, but are clinically asymptomatic. These findings support that outpatient initiation of propranolol in healthy, normotensive infants appears to be a relatively safe alternative to inpatient initiation. Hypoglycemia is rare, but can occur throughout the treatment period; parent counseling is of paramount importance. PMID- 24224398 TI - Measurement of phonation threshold power in normal and disordered voice production. AB - OBJECTIVES: Phonation threshold pressure (PTP) and phonation threshold flow (PTF) are useful aerodynamic parameters, but each is sensitive to different disorders. A single comprehensive aerodynamic parameter sensitive to a variety of disorders might be beneficial in quantitative voice assessment. We performed the first study of phonation threshold power (PTW) in human subjects. METHODS: PTP and PTF were measured in 100 normal subjects, 19 subjects with vocal fold immobility, and 94 subjects with a benign mass lesion. PTW was calculated from these two parameters. In 41 subjects with a polyp, measurements were obtained before and after excision. Receiver operating characteristic (ROC) analysis was used to determine the ability of the three parameters to distinguish between controls and disordered groups. RESULTS: The PTW (p < 0.001), PTP (p < 0.001), and PTF (p < 0.001) were different among the three groups. All parameters decreased after polyp excision. PTW had the highest area under the ROC curve for all analyses. CONCLUSIONS: PTW is sensitive to the presence of mass lesions and vocal fold mobility disorders. Additionally, changes in PTW can be observed after excision of mass lesions. PTW could be a useful parameter to describe the aerodynamic inputs to voice production. PMID- 24224399 TI - Muscular anatomy of the human ventricular folds. AB - OBJECTIVES: Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. METHODS: Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. RESULTS: The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. CONCLUSIONS: Although variability of expression was evident, a well defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens. PMID- 24224400 TI - Comparison of carbon dioxide laser-assisted versus stapler-assisted endoscopic cricopharyngeal myotomy. AB - OBJECTIVES: We directly compared endoscopic carbon dioxide (CO2) laser and stapler treatment methods for both cricopharyngeal hypertrophy (CPH) and Zenker's diverticulum (ZD). METHODS: We performed a single-institution retrospective chart review of 153 patients who underwent either CO2 laser-assisted or stapler assisted endoscopic cricopharyngeal myotomy (CPM). RESULTS: Isolated CPH was more likely to be treated with the CO2 laser than by stapler techniques. The ZD pouch size decreased significantly after surgery in both laser (p = 0.04) and stapler (p = 0.008) groups. The average duration of the procedure for CPM was longer for the laser than for the stapler (p = 0.01). Both techniques were successful when used in revision procedures. The overall complication rates were not statistically significantly different. Laser surgery trended toward a higher rate of major complications (2.4% versus 0%). Symptomatic recurrence was more likely after stapler surgery (p = 0.002). The rates of revision surgery were similar in the two groups (3.3% for laser and 4.3% for stapler). CONCLUSIONS: In the treatment of isolated CPH or ZD, stapler-assisted endoscopic surgery results in a shorter operative time, whereas laser-assisted CPM results in a decreased incidence of symptomatic recurrence. PMID- 24224401 TI - Laryngeal obstruction by cervical and endolaryngeal lymphatic malformations in children: proposed staging system and review of treatment. AB - OBJECTIVES: We review and stage a series of congenital lymphatic malformations (LMs) that caused laryngeal obstruction according to a proposed staging system, review the treatment modalities utilized, and correlate the stage of disease with clinical outcomes and tracheotomy statuses. METHODS: We present a detailed description of the clinical presentation, management approach, and clinical outcome and tracheotomy status of a series of patients with laryngeal obstruction by LMs. A 4-part staging system (stages I to IV) for congenital LMs obstructing the larynx, based upon our clinical experience, is proposed. The patients were retrospectively reviewed and staged according to the proposed system, and clinical management and outcomes were correlated with the stage of disease. RESULTS: We identified 16 patients with laryngeal obstruction by LMs. Eighty-one percent (13 of 16) received sclerotherapy, and 50% (8 of 16) underwent operative excision or debridement. Forty percent (2 of 5) of stage I lesions, 75% (3 of 4) of stage II lesions, 100% (4 of 4) of stage III lesions, and 100% (3 of 3) of stage IV lesions were in patients who required tracheotomy. All patients who had stage I and II lesions and required tracheotomy have been decannulated, whereas only 2 of the 4 patients with stage III lesions and no patients with stage IV lesions have been successfully decannulated. CONCLUSIONS: Lymphatic malformations obstructing the larynx require a careful and often staged management approach. A proposed staging system helps to predict the need for tracheotomy and the likelihood of long-term tracheotomy dependence. PMID- 24224402 TI - Bone-anchored hearing devices in children with unilateral conductive hearing loss: a patient-carer perspective. AB - OBJECTIVES: We sought to determine the outcome of implantation of a bone-anchored hearing device in children with unilateral conductive hearing loss. METHODS: A retrospective case note analysis was used in a tertiary referral pediatric hospital to study 17 consecutive cases of pediatric patients with unilateral conductive hearing loss who were fitted with a bone-anchored hearing device between 2005 and 2010. RESULTS: The average age of the patients at the time of bone-anchored hearing device fitting was 10 years 6 months (range, 6 years 3 months to 16 years). Qualitative subjective outcome measures demonstrated benefit. The vast majority of patients reported improved social and physical functioning and improved quality of life. All 17 patients are currently using their bone-anchored hearing device on a daily basis after a follow-up of 6 months. CONCLUSIONS: This study has shown improved quality of life in children with unilateral hearing loss after implantation of their bone-anchored hearing device. There was a high degree of patient satisfaction and improvement in health status reported by children and/or carers. Bone-anchored hearing devices have an important role in the management of children with symptomatic unilateral hearing loss. Perhaps earlier consideration of a bone-anchored hearing device would be appropriate in selected cases. PMID- 24224403 TI - Subacute rhinitis in infants: gastroesophageal reflux must be considered. AB - OBJECTIVES: The study sought to evaluate the influence of gastroesophageal reflux disease (GERD) and allergy on subacute rhinitis in infants. METHODS: Mothers of 74 infants with subacute rhinitis completed the Infant Gastroesophageal Reflux Questionnaire Revised. Participants with GERD were randomized to undergo one of the following regimens for 10 days: use of fluorometholone nasal drops with positional and feeding changes; positional and feeding changes; or a placebo. RESULTS: The daily amount of nasal secretion decreased by 75.9% (p < 0.001), the intensity of swallowing difficulty by 79.2% (p < 0.001), and the incidence of uneasiness by 92.0% (p < 0.001) in infants treated with nasal glucocorticoid and positional and feeding changes; and the percentage differences in the amount of nasal secretion (p < 0.001), feeding difficulty (p < 0.001), and uneasiness (p < 0.001) were greater than those in the group treated with positional and feeding changes. The infants treated with placebo did not improve. The influence of nasal allergy was nonsignificant. CONCLUSIONS: Gastroesophageal reflux disease might contribute to aggravation of subacute rhinitis in infants. PMID- 24224404 TI - Caffeic acid phenethyl ester inhibits diesel exhaust particle-induced inflammation of human middle ear epithelial cells via NOX4 inhibition. AB - OBJECTIVES: Otitis media is one of the most common diseases in pediatric populations. Recent research on its pathogenesis has focused on air pollution. Chronic exposure to particulate air pollution is associated with the impairment of middle ear function. However, the mechanisms and the underlying inhibitory pathways, especially in the human middle ear, remain unknown. Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis, a product of honeybee hives, which has anti-oxidative and anti-inflammatory activities. The aim of this study was to evaluate the inhibitory effect of CAPE on diesel exhaust particle (DEP)-induced inflammation of human middle ear epithelial cells and to determine the underlying pathway of the action of CAPE. METHODS: The inflammatory damage caused by DEPs and the anti-inflammatory effects of CAPE were determined by measuring the levels of tumor necrosis factor alpha and nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 with real-time reverse transcription polymerase chain reaction and Western blot analysis. The oxidative stress induced by DEPs and the anti-oxidative effects of CAPE were directly evaluated by measuring reactive oxygen species production by use of flow cytometric analysis of 2',7'-dichlorofluorescein diacetate. The effects of CAPE were compared with those of N-acetyl-L-cysteine, which has anti-oxidative and anti-inflammatory effects. RESULTS: Use of CAPE significantly inhibited DEP-induced up-regulation of tumor necrosis factor alpha and NOX4 expression in a dose- and time-dependent manner. The accumulation of reactive oxygen species induced by DEPs was decreased by pretreatment with CAPE. The anti-inflammatory and anti-oxidative effects of CAPE were similar to those of N-acetyl-L-cysteine. CONCLUSIONS: The inflammation induced by DEP is reduced by CAPE via the inhibition of NOX4 expression. These findings suggest that CAPE might be used as a therapeutic agent against DEP induced inflammation of human middle ear epithelial cells. PMID- 24224405 TI - Comparison between transcatheter and surgical aortic valve replacement: a single center experience. AB - BACKGROUND AND AIM OF THE STUDY: A comparison was made of the outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (AVR) in high-risk patients. METHODS: All patients aged > 75 years that underwent a procedure for severe aortic stenosis with or without coronary revascularization at the authors' institution were included in the study; thus, 64 patients underwent TAVI and 188 underwent AVR. Patients in the TAVI group were older (mean age 84 +/- 5 versus 80 +/- 4 years; p < 0.0001) and had a higher logistic EuroSCORE (p = 0.004). RESULTS: Six patients (9%) died during the procedure in the TAVI group, and 23 (12%) died in the AVR group (p = 0.5). Predictors for mortality were: age (p < 0.0001), female gender (p = 0.02), and surgical valve replacement (p = 0.01). Gradients across the implanted valves at one to three months postoperatively were lower in the TAVI group (p < 0.0001). Actuarial survival at one, two and three years was 78%, 64% and 64%, respectively, for TAVI, and 83%, 78% and 75%, respectively, for AVR (p = 0.4). Age was the only predictor for late mortality (p < 0.0001). CONCLUSION: TAVI patients were older and posed a higher predicted surgical risk. Procedural mortality was lower in the TAVI group, but mid-term survival was similar to that in patients undergoing surgical AVR. Age was the only predictor for late survival. These data support the referral of high-risk patients for TAVI. PMID- 24224406 TI - Advanced age per se should not be an exclusion criterion for minimally invasive aortic valve replacement. AB - BACKGROUND AND AIM OF THE STUDY: The introduction of transcatheter aortic valve implantation (TAVI), coupled with the increasing number of elderly patients requiring cardiac surgery, has given rise to an intense debate on the most appropriate treatment strategy for this high-risk population. The study aim was to compare clinical outcomes in older versus younger patients undergoing minimally invasive aortic valve replacement (AVR). METHODS: Between March 2010 and July 2012, 66 patients undergoing minimally invasive isolated AVR with the sutureless Perceval S bioprosthesis (Sorin Group, Saluggia, Italy) were allocated to two groups according to age > or = 80 years (group A, n = 25) or < 80 years (group B, n = 41). In-hospital and follow up data were collected for all patients, including an evaluation of the patients' quality of life, using the SF 36 questionnaire. RESULTS: Mean age and logistic EuroSCORE were statistically different between groups (p < 0.001 and p = 0.002, respectively). The length of intensive care unit stay was similar in groups A and B (1.9 +/- 0.8 and 2.5 +/- 1.4 days, respectively; p = 0.061). In-hospital mortality occurred in only one patient of group A (1.5%). Postoperative transient cerebral ischemic events occurred with similar frequency in both groups (two in group A and four in group B; p = 0.59). One patient in group A and two patients in group B required pacemaker implantation (1.5 versus 3%; p = 0.68). The mean follow up was 13.9 +/- 7.4 months, during which time three patients died (two in group A, one in group B). All enrolled patients answered the SF-36 questionnaire, and there were no significant differences between groups in all eight domains of the test. CONCLUSION: Within the setting of minimally invasive isolated AVR, the study results showed that the clinical outcomes and quality of life in patients aged > or = 80 years were comparable to those of younger patients. Therefore, advanced age per se does not preclude successful AVR through a minimally invasive approach. PMID- 24224407 TI - Percutaneous temporary aortic valve: a proof-of-concept animal model. AB - BACKGROUND AND AIM OF THE STUDY: An early prototype of a temporary aortic valve (TAV) catheter system was evaluated for its potential to serve as an integrated device for aortic valve intervention and replacement. The prototype consisted of two essential components: a central catheter for the delivery of aortic valve interventional tools (valve debulking, resection, replacement); and a balloon inflatable temporary valve for hemodynamic support when the native aortic valve is removed. After valve replacement, the TAV catheter system is designed to be readily withdrawn from the subject. METHODS: Individual aspects of both components of the prototype were examined in experiments with four pigs. The central catheter was used to deliver a self-expanding stent for native aortic valve ablation to create acute severe aortic insufficiency (AI). The balloon-TAV was deployed in the proximal aorta to control the induced AI. Electrocardiographic (ECG), cardiac output (CO), pulmonary wedge pressure (PWP), left ventricular (LV) pressure, and aortic pressure proximal and distal from the TAV were recorded. RESULTS: The central catheter was successful in delivering and deploying the valve ablation stent at the annulus to create massive AI; the LV diastolic pressure was increased from 12.6 +/- 1.1 to 32.4 +/- 2.0 mmHg (p < 0.001) with valve ablation. The deployed TAV in the proximal aorta led to a re narrowing of the distal pulse pressure with a drop in the LV diastolic pressure to 21.5 +/- 1.5 mmHg (p < 0.001). During TAV support, some PWP lowering and a CO rise occurred, but these did not achieve statistical significance; no significant acute ECG changes were noted. CONCLUSION: In this early prototype, the TAV catheter system demonstrated the potential to serve as an integrated device for both aortic valve modification and replacement. PMID- 24224408 TI - Optimal results of aortic valve replacement with small mechanical valves (< 19 mm). AB - BACKGROUND AND AIM OF THE STUDY: Controversy exists regarding the optimal operative method or type of prosthesis for patients with a small aortic root. The aim of this retrospective study was to investigate the early and mid-term outcomes of standard aortic valve replacement (AVR) using 16 mm or 18 mm ATS Advanced Performance (AP) or 17 mm St. Jude Medical (SJM) Regent valves for a small aortic root. METHODS: Between April 2003 and August 2009, 78 patients (age range: 50-86 years; 86% aged > or = 65 years) underwent AVR with 16 mm or 18 mm ATS AP valves (16AP group: n = 21, 18AP group: n = 32), or a 17 mm SJM Regent valve (17Regent group: n = 25). Fifty-six patients (72%) had a body surface area (BSA) of < 1.5 m2; the BSA in the 16AP group was significantly smaller than in the other two groups. The early and mid-term outcomes, and the hemodynamic performance of the prostheses, were evaluated and compared among the groups. RESULTS: No operative deaths were observed in the 16AP and 17Regent groups, but one hospital death occurred in the 18AP group. During follow up, there were four cardiac-related deaths (two patients each in the 16AP and 18AP groups). Although the postoperative pressure gradient of the 16AP group was significantly higher than that of the 18AP group, the left ventricular mass in all groups was decreased significantly during follow up, but the extent of left ventricular mass regression was similar among the groups (-30%, -25% and -28% in the 16AP, 17Regent and 18AP groups, respectively; p = 0.844). CONCLUSION: The early and mid term results of AVR with 16 mm or 18 mm ATS AP valves, or with a 17 mm SJM Regent valve, were satisfactory. Therefore, standard AVR using these small mechanical prostheses, which avoids the need to enlarge the annulus or to conduct stentless bioprosthesis implantation, might represent an acceptable method, especially in elderly patients with a small aortic root. PMID- 24224409 TI - Relationship between morphologic features of myocardial tissue and left ventricular function in patients with aortic valve disease and left ventricular hypertrophy. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the correlation of myocardial fibrosis with myocardial remodeling and clinical outcome of aortic valve replacement (AVR) in patients with aortic stenosis and left ventricular (LV) hypertrophy. METHODS: Between 2007 and 2010, a total of 43 patients (23 males, 20 females; mean age 65.5 +/- 10.6 years; range: 33-84 years) underwent AVR at the authors' institution. During surgery, specimens (10 mm3) were obtained from the LV outflow tract and stained with Masson's trichrome. The fibrosis fraction (FF) was quantified. The mean follow up duration was 18.8 +/- 12.2 months (range: 0-46 months). Patients were allocated to either of two groups: the lower fibrosis (LF) group (n = 24) with FF < 5%, and the higher fibrosis (HF) group (n = 19) with FF > or = 5%. RESULTS: There were no significant differences between the two groups in terms of preoperative NYHA functional class and complications. In total, 33 patients (19 LF and 14 HF) were followed up for at least six months. The preoperative LV mass index (LVMI) and LV ejection fraction (LVEF) were not significantly different between the two groups (p = 0.805 and p = 0.377, respectively). At the last follow up examination the LVMI showed a significant inter-group difference (LF group 111.4 +/- 23.2 g/m2; HF group 91.9 +/- 21.5 g/m2; p = 0.005), but the LVEF did not differ significantly between groups (p = 0.457). There was one early (non-cardiac) death in the LF group, and one early death and one late death (both cardiac-related) in the HF group. CONCLUSION: In patients with aortic stenosis, a higher LVMI was not related to more severe myocardial fibrosis, and LV mass regression after AVR was not influenced by the severity of the myocardial fibrosis. Rather, cardiac-related death might be related to a highly fibrotic heart. PMID- 24224410 TI - Aortic valve leaflet glycosaminoglycans composition and modification in severe chronic valve regurgitation. AB - BACKGROUND AND AIM OF THE STUDY: The surgical segments of aortic valve leaflets from patients with severe chronic aortic regurgitation were analyzed (by percentage and structure) for their content of complex polysaccharides and glycosaminoglycans (GAGs), and compared with control segments. METHODS: The GAG, hyaluronic acid (HA), chondroitin sulfate (CS) and dermatan sulfate (DS) and disaccharide contents were determined in segments (leaflet, root attachment region and belly) of aortic valve leaflets (non-coronary, left coronary and right coronary) using a multi-analytical approach. RESULTS: The aortic valve leaflets showed the presence of HA and CS/DS, with an overall charge density of -0.51 0.55. The CS/DS polymers showed a 4-sulfated/6-sulfated ratio of -0.70-0.77 in the belly, and -1.60-1.72 in commissure parts (-/+124%). The total amount of GAGs was -1.60-2.40 microg/mg of tissue. A significant increase in sulfated GAGs was observed in all valve parts in patients suffering from severe aortic insufficiency, as well as an increase in the 4-sulfated/6-sulfated ratio in the leaflet belly (-/+102%). CONCLUSION: It is speculated that differences in 4 sulfated/6-sulfated ratio determined in the belly and leaflet attachment region commissure parts of the leaflets may correlate with the tensile or compressive loading of normal aortic valve regions. At the same time, it may be assumed that the increase in sulfated GAGs and 4-sulfated/6-sulfated ratio in the leaflet belly of valves taken from patients suffering severe aortic insufficiency was consistent with an altered matrix microstructure capable of influencing the hydration of these pathological tissues, and of conditioning their mechanical weakness. PMID- 24224411 TI - Evaluation of cardiac valvular regurgitant lesions by cardiac MRI sequences: comparison of a four-valve semi-quantitative versus quantitative approach. AB - BACKGROUND AND AIM OF THE STUDY: Cardiac magnetic resonance (CMR) imaging generally allows a more accurate and valid quantification of cardiac function, mass and regurgitant volumes than echocardiography. Although recent technological advancements in CMR have made the evaluation of cardiac valves more reliable, no studies have yet been conducted to compare semi-quantitative grading (SQG) using CMR steady-state free precession (SSFP) sequences with quantitative grading (QG) based on stroke volumes and phase-velocity mapping (PVM). It is proposed that the SQG of cardiac valvular regurgitations based on CMR SSFP sequences is feasible, and highly correlative with standard CMR QG methods. METHODS: CMR data obtained between January 2007 and December 2011 was evaluated prospectively for valvular regurgitant lesions. Patients were included if they had right and left ventricular volumetrics based on CMR SSFP sequences and PVM across the aortic and pulmonic valves with reported regurgitant volumes and fractions. Patients were excluded if they had prosthetic valves, cardiac arrhythmias and intra-cardiac shunts. Regurgitant lesions were semi-quantitatively (visually) graded on a standard scale of 0 to 4 (trace, mild, moderate, moderate to severe, and severe) and compared with quantitative regurgitant fractions. Correlations were evaluated by Spearman's rho formula, and kappa for intra- and inter-observer variabilities were obtained on 30% of the study sample. RESULTS: A total of 97 patients (58 males, 39 females; average age 55 +/- 18 years) representing 134 valvular regurgitations [mitral (MR), aortic (AR), tricuspid (TR), and pulmonary (PR)] were analyzed by semiquantitative and quantitative methods. The regurgitant lesions included 44 mitral, 50 aortic, 29 tricuspid, and 11 pulmonary. The correlation between SQR versus QG yielded the following results: 0.67, p < 0.001 (MR, r = 0.66, p < 0.001; AR, r = 0.68, p < 0.002; TR, r = 0.68, p = 0.001; PR, r = 0.70, p = 0.017). The results for QG versus SQG accounting for clinically significant differences of +/- 1 grade for the group were as follows: 0.95, p < 0.001 (MR, r = 0.91, p < 0.001; AR, r = 0.96, p < 0.001; TR, r = 0.99, p < 0.001; PR, r = 0.93, p < 0.001). No discrepancy between surgical regurgitation was present (3+ versus 4+). Weighted kappa results were 0.67 and 0.61 for intra- and inter-observer variabilities. CONCLUSION: The visual assessment of cardiac regurgitant lesions is reliable, accurate and reproducible when compared to formal quantitative analysis via CMR. This confirms a robust role for CMR in assessing regurgitant lesions, particularly for surgical decision-making. These results were applicable to patients in sinus rhythm at the time of scanning. PMID- 24224413 TI - Impact of postoperative cusp configuration on midterm durability after aortic root reimplantation. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to examine the echocardiographic features associated with recurrent aortic regurgitation (AR) after valve-preserving aortic root reconstruction surgery. METHODS: Echocardiographic data from 86 patients who underwent aortic root replacement with or without cusp repair were retrospectively reviewed. An analysis was conducted of the height difference between the level of the ventriculoaortic junction (VAJ) and the central free margin of the cusp, defined as the effective height (EH), and the length from the aortic annulus to the edge of the body of Arantius, defined as the geometric height (GH), in addition to root dimensions (diameter of VAJ, sinus of Valsalva, and sinotubular junction). RESULTS: All patients presented with < or = mild AR at discharge. After a median follow up duration of 46.4 months, the development of moderate AR or greater was observed in 14 patients. The overall actuarial freedom from moderate AR or greater, and freedom from reoperation at three and five years were 86.2 +/- 4.4% and 81.8 +/- 5.2%, and 94.0 +/- 3.0% and 91.8 +/- 3.6%, respectively. The postoperative EH (7.47 +/- 3.3 mm in > mild AR group, versus 8.81 +/- 2.1 mm in < or = mild AR group, p = 0.049), the incidence of postoperative eccentric jet (57.1% in > mild AR group versus 12.5% in < or = mild AR group, p = 0.0005) and cusp billowing (78.6% in > mild AR group versus 20.8% in < or = mild AR group, p < 0.0001) were significantly correlated with > mild AR in the follow up. There was also correlation between postoperative EH and the severity of recurrent AR at follow up (p = -0.33, p = 0.0019). CONCLUSION: Objective information on cusp configuration, such as EH, should play an important role in stabilizing the outcome of valve-sparing surgery. PMID- 24224412 TI - Aortic root replacement with a stented bioprosthetic valved conduit: mid-term results. AB - BACKGROUND AND AIM OF THE STUDY: For patients who require aortic root replacement but are unwilling or unable to receive anticoagulants, a composite conduit was assembled intraoperatively that contained a stented biological valve sutured inside a vascular tube graft, rather than at its extremity. This simple modification of the Bentall concept may provide several advantages. The results obtained with this conduit over an 11-year period were analyzed. METHODS: Between May 2001 and April 2012, 101 consecutive patients (mean age 68.3 +/- 9.2 years) underwent aortic root replacement with the bioprosthetic valved conduit. Aortic pathologies included degenerative disease in 61 patients (60.4%), atherosclerosis in 20 (19.8%), annuloaortic ectasia in 12 (11.9%), porcelain aorta in four (4.0%), and acute dissection in four (4.0%). The whole ascending aorta was replaced in 79 patients (78.2%); a hemiarch reconstruction and a total arch replacement were added in 18 (17.8%) and four (4.0%) patients, respectively. Hypothermic circulatory arrest was performed in 60 cases (59.4%). Forty patients (39.6%) underwent additional cardiac procedures. All perioperative data were collected prospectively. RESULTS: There were five (5.0%) hospital deaths. During a mean follow up of 3.8 +/- 2.4 years there were two non-valve-related cardiac deaths and five noncardiac deaths. The seven-year actuarial survival was 79.2% (95% CI 67.0-91.4%). Bioprosthetic structural dysfunction occurred in only one patient; reoperation was easily performed by replacing the valve within the vascular graft. In the remaining 88 patients (87.1%), echocardiographic assessment showed a low transaortic mean pressure gradient (7.2 +/- 4.7 mmHg) and left ventricular wall mass reduction (p = 0.0002). CONCLUSION: This valved conduit is a safe and durable option for replacing the aortic root, thus facilitating the technique of implantation and simplifying reoperation in the case of valve failure. PMID- 24224414 TI - Predictive value of five risk scores to predict outcomes after aortic valve replacement in octogenarians. AB - BACKGROUND AND AIM OF THE STUDY: Operative risk is assessed preoperatively through the use of predictive scores. The study aim was to evaluate the validity of five different scoring systems, including the Society of Thoracic Surgeons (STS) score, additive and logistic European systems (EuroSCORE 1) for cardiac operative risk evaluation, EuroSCORE 2, and the Ambler score in octogenarian patients undergoing aortic valve replacement (AVR). METHODS: A total of 225 patients aged > or = 80 years with aortic stenosis underwent isolated AVR between January 1996 and September 2010. All five scores were evaluated with regards to their accuracy in predicting operative mortality, mortality at one year, and the capacity to identify those patients most likely to die during long-term follow up. RESULTS: The observed operative mortality rate was 7.6%. The observed/expected ratios calculated for perioperative mortality were 0.42, 0.87, 1.16 and 1.16 for the logistic EuroSCORE, Ambler score, STS score and EuroSCORE 2 cohorts, respectively. The Hosmer-Lemeshow statistical test showed that all five scores were well calibrated. The STS score was a good test for predicting operative mortality (AUC 0.81) and the EuroSCORE 2 was fair (AUC 0.72). In terms of predicting the one-year mortality rate, the STS score was ranked as fair (AUC > 0.7). It was noted that patients with a STS score > or = 75th percentile were more likely to die during the follow up period. CONCLUSION: The STS score appeared to be more adequate for predicting operative mortality among patients aged > or = 80 years. STS scores were predictive of both one-year and long-term survival rates. These results indicated that the STS score could be used to guide clinical decision-making for performing AVR in elderly patients. PMID- 24224415 TI - Surgical relocation of the papillary muscles in functional ischemic mitral regurgitation: what are the forces of the relocation stitches acting on the myocardium? AB - BACKGROUND AND AIM OF THE STUDY: In patients with chronic functional ischemic mitral regurgitation (FIMR), papillary muscle relocation has the potential to induce reverse left ventricular remodeling. However, in order to optimize function and durability, the forces imposed on the left ventricular myocardium by papillary muscle relocation should be assessed. METHODS: Eight pigs with FIMR were subjected to down-sized ring annuloplasty in combination with relocation of the anterior (5 mm) and posterior (15 mm) papillary muscles towards the respective trigone. Papillary muscle relocation was obtained by a 2-0 expanded polytetrafluoroethylene stitch fixed to the trigone, exteriorized through the myocardium overlying the papillary muscle, and fixed to an epicardial disc. Tension in these stitches was measured at a systolic blood pressure > 80 mmHg using a custom-made sliding caliper with a strain gauge mounted in line. This allowed assessment of the cyclic change from minimal diastolic to maximum systolic papillary muscle relocation stitch tension. RESULTS: Maximum cyclic change in the posterior papillary muscle (PPM) stitch tension was 1.1 N at 15 mm relocation. In comparison, the anterior papillary muscle (APM) tension was increased to a maximum of 1.4 N with only 5 mm relocation. Surprisingly, during each step of isolated PPM relocation, the APM stitch tension increased concomitantly, but in contrast APM relocation did not influence the magnitude of PPM stitch tension. There was no statistically significant difference between cyclic changes in APM and PPM stitch tension at any step of relocation. CONCLUSION: Papillary muscle relocation using stitches attached between epicardial discs and respective trigones induced a cyclic change in papillary muscle relocation stitch tension of 1.1-1.4 N. These values were in the range of normal tension in the mitral valve apparatus, and equivalent to only 19-24% of the total papillary muscle forces. Therefore, this technique does not appear to induce a non-physiologically high cyclic load on the mitral valve complex. PMID- 24224416 TI - Mitral valve resistance correlates more closely with left atrial deformation than with conventional indices of rheumatic mitral stenosis. AB - BACKGROUND AND AIM OF THE STUDY: The relationship between mitral valve (MV) resistance and left atrial (LA) mechanical function is unknown. Hence, the study aim was to investigate the relationship between LA mechanics and MV resistance, compared to conventional indices such as mitral valve area (MVA) and transmitral gradient, in patients with rheumatic mitral stenosis (MS). METHODS: The study population consisted of 73 patients with MS and 30 age- and gender-matched controls. MV resistance was calculated and LA strain parameters were assessed from the apical four-chamber view by speckle tracking echocardiography (LA reservoir strain, LA pump strain, LA strain rate (SR)) in all subjects. RESULTS: The MS group has a markedly higher MV resistance (94 +/- 46 versus 67 +/- 22 dynes x s x cm(-5), p = 0.003) and lower LA reservoir strain (24.5 +/- 7.4% versus 36.6 +/- 3.8%, p < 0.001), LA pump strain (12.0 +/- 5.0% versus 17.1 +/- 3.4%, p < 0.001) and SR (1.23 +/- 0.33 versus 1.4 +/- 0.29, p = 0.017) values compared to controls. Moreover, both LA reservoir strain and LA pump strain correlated with MV resistance more closely than did MVA and transmitral gradients. Multiple linear regression analysis revealed only MV resistance to be an independent predictor of LA reservoir strain, while MV resistance, indexed left atrial volume and mean gradient were independent predictors of LA pump strain. CONCLUSION: It can be concluded that, in patients with MS, mitral valve resistance was more closely related to LA mechanics measurements than were conventional indices of MS. PMID- 24224417 TI - Mitral subvalvular plasty for chronic ischemic mitral regurgitation: a preliminary experimental model. AB - BACKGROUND AND AIM OF THE STUDY: Restrictive annuloplasty remains the most widespread technique for the correction of chronic ischemic mitral regurgitation (IMR). However, this technique only partially corrects the underlying pathophysiology and does not address the restricted leaflet motions during systole that result from progressive left ventricular (LV) remodeling. METHODS: A novel experimental model of IMR was developed using an isolated pig heart placed on a hydrodynamic test-stand. A T-shaped LV patch was sutured onto the posterior wall of the left ventricle to simulate LV dilatation secondary to post-MI remodeling. RESULTS: Using this model, a novel technique of subvalvular mitral valvuloplasty was described that reduces the distance between the posterior mitral annulus and the papillary muscle base and appears to be effective in eliminating IMR. Pledgetted 2-0 non-absorbable sutures were placed at the base of one papillary muscle, then through the other papillary muscle and then brought to the posterior mitral annulus. The same sequence was repeated in the other direction. A specific formula was then used to calculate the length of the subvalvular support prior to suture tying. CONCLUSION: Subvalvular support of the mitral apparatus in chronic IMR can be achieved using this simple method, which appears to be effective in eliminating IMR. Further data relating to the use of this technique in the clinical setting as an adjunct to mitral annuloplasty are forthcoming. PMID- 24224418 TI - Three-dimensional echocardiographic assessment before and after percutaneous transvenous mitral commissurotomy in patients with rheumatic mitral stenosis. AB - BACKGROUND AND AIM OF THE STUDY: Real-time three-dimensional transthoracic echocardiography (RT3DE) is a relatively recent imaging technique that provides excellent image quality of the mitral valve. It has been suggested that this new echocardiographic modality, which allows a precise cross-section of the mitral orifice at the tips of the leaflets with correct plane orientation, may provide a more accurate assessment of rheumatic mitral stenosis (MS) than two-dimensional echocardiography (2DE), before and after percutaneous transvenous mitral commissurotomy (PTMC). METHODS: A total of 50 patients with symptomatic mitral stenosis who underwent PTMC was evaluated prospectively. Patients in all age groups, with evidence of severe MS admitted to the authors' institution, in whom PTMC was feasible were included. RESULTS: A good valve opening was observed in 45 patients (90%). The mitral valve area (MVA) assessed before PTMC with 3DE (3D MVA) correlated well with that assessed with 2DE (2D-MVA) (0.85 +/- 0.12 cm2 versus 0.86 +/- 0.13 cm2, p < 0.001); the mean difference between methods was small (0.01 +/- 0.11 cm2) and correlation excellent (r = 0.64, p < 0.001). After PTMC, values of 3D-MVA did not differ from, and correlated well with, values of 2D-MVA (1.79 +/- 0.20 cm2 versus 1.74 +/- 0.18 cm2, p = 0.006); the mean difference between methods was small (0.05 +/- 0.02 cm2) and correlation excellent (r = 0.76, p = 0.0001). Before PTMC, Bland-Altman analysis showed a good agreement between methods (mean difference -0.01 +/- 0.11 cm2, lower limit 0.24, upper limit 0.22). After PTMC, Bland-Altman analysis showed a good agreement between methods (mean difference -0.05 +/- 0.13 cm2, lower limit -0.3, upper limit 0.2). Evaluation of the commissural opening after PTMC, using RT3DE, showed that excellent commissural evaluation was possible in all patients. Compared with RT3DE, an underestimation of the degree of commissural fusion using 2DE was observed in 32%, with a weak agreement between methods. CONCLUSION: RT3DE provided accurate measurements of MVA, similar to 2D planimetry. RT3DE also improved the description of valvular anatomy and provided a unique assessment of the extent of commissural splitting. PMID- 24224419 TI - Impact of rheumatic mitral stenosis on aortic elastic properties. AB - BACKGROUND AND AIM OF THE STUDY: Although mitral stenosis has profound effects on the circulation and hemodynamics, few data exist regarding its impact on aortic elastic properties. The study aim was to determine the association between mitral stenosis and aortic elastic properties by using strain and distensibility as a surrogate. METHODS: Sixty-six patients with echocardiographic documentation of rheumatic mitral stenosis, and 25 age- and gender-matched healthy control subjects were enrolled in the study. Aortic elasticity parameters including strain and distensibility were measured by means of echocardiography. RESULTS: The mean age of the patient and control groups were 41.8 +/- 12.0 and 38.9 +/- 5.0 years, respectively (p = 0.12). There was a significant impairment in distensibility and strain in the patient group compared to controls (0.276 +/- 0.167 versus 0.491 +/- 0.260 cm2 x dyn(-1), p = 0.001; 6.54 +/- 3.18% versus 9.19 +/- 4.78%, p = 0.015). There was a strong correlation between distensibility and left atrial diameter (p < 0.001; r = -0.39), left atrial volume index (p < 0.001; r = -0.56), mitral valve area (p < 0.001; r = 0.40), and mean transmitral gradient (p = 0.022; r = -0.18). Strain was also associated with left atrial diameter (p = 0.002; r = -0.32), left atrial volume index (p < 0.001; r = -0.41), mitral valve area (p = 0.002; r = 0.31), and mean transmitral gradient (p = 0.035; r = -0.18). CONCLUSION: Mitral stenosis was shown to be associated with impaired aortic elasticity, but further studies are required to clarify the clinical significance of this finding. PMID- 24224420 TI - Symmetrical papillary muscle approximation for functional mitral regurgitation with idiopathic dilated cardiomyopathy. AB - The cases are reported of mitral valve repair with symmetrical papillary muscle approximation from heads to bases close to cardiac apex for functional mitral regurgitation (FMR). The two papillary heads attaching the chordae to both leaflets from the posteromedial papillary muscle were approximated parallel to the solitary head of the anterolateral papillary muscle. This procedure permits an even reduction of lateral shift of the papillary muscle, resulting in an elimination of mitral tethering, and provides a satisfactory and durable mitral valve repair with good outcomes in patients with idiopathic dilated cardiomyopathy and FMR. PMID- 24224421 TI - Fresh autologous pericardium for leaflet perforation repair in mitral valve infective endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: There is clear evidence that mitral valve (MV) repair is superior to replacement for MV infective endocarditis (IE). Leaflet perforation is a common pathologic finding in MV IE, and leaflet patch repair with glutaraldehyde-treated autologous or bovine pericardium is the currently accepted method of MV repair. In the present study, fresh autologous pericardium (FAP) was used universally to treat leaflet perforation in MV IE, and the mid term clinical and echocardiographic outcomes were determined. METHODS: Between 2002 and 2009, a total of 20 patients with leaflet perforations from MV IE underwent patch repair with FAP. Follow up echocardiography was performed in a core laboratory. RESULTS: There was one operative death (5%) secondary to sepsis, and three late deaths (15%). Late echocardiograms were available for review from 16 of the 19 patients (84%) who survived surgery. The mean time to follow up echocardiography was 793 +/- 663 days. The mitral regurgitation (MR) grade was mild or less in 14/16 patients (88%), moderate in one patient (6%), and severe in one patient (6%). The mean gradient was 4.8 +/- 2.7 mmHg, and the ejection fraction was preserved in all patients (63 +/- 4%). No expansion, retraction or calcification of the patches was observed. Freedom from reoperation, reinfection and thromboembolism was 100%. CONCLUSION: Fresh autologous pericardium for MV leaflet patch repair in IE is associated with good mid-term valve function. Given the association between late calcification and the glutaraldehyde treatment of bioprosthetic valves and this favorable experience, it is believed that FAP is an acceptable alternative for leaflet repair in MV IE. PMID- 24224422 TI - Comparison between early and late prosthetic valve endocarditis: clinical characteristics and outcomes. AB - BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) is considered a time-related event. The study aim was to compare the clinical characteristics and outcomes of early- and late-onset PVE, and to investigate potential preventive measures for each condition. METHODS: A total of 47 consecutive patients undergoing surgery for PVE between January 1986 and December 2011 were analyzed retrospectively, and classified as an early-onset group (n = 26; PVE occurring within 12 months after previous surgery) and late-onset group (n = 21; PVE occurring after 12 months). RESULTS: The prosthetic valve position significantly affected the incidence of endocarditis: 21 cases (80.7%) in the early-onset group had infected aortic prostheses, while 18 (85.7%) in the late onset group had infected mitral prostheses (p = 0.028). PVE significantly affected bioprosthetic valves in the early-onset group (18 cases, 69.2%) and mechanical valves in the late-onset group (17 cases, 80.9%) (p < 0.01). Staphylococcus spp. infections were predominant in the early-onset group (21 cases, 80.7%), and Streptococcus spp. in the late-onset group (five cases, 23.8%) (p = 0.03). Operative deaths occurred in both the early-onset (n = 6; 23.0%) and late-onset (n = 2; 9.5%) groups (p = 0.11). The long-term mortality in the early onset and late-onset groups, respectively, was 40.3 +/- 17.7% and 85.1 +/- 7.9% at 10 years, and 40.3 +/- 17.7% and 72.9 +/- 13.1% at 15 years (p 0.047). Freedom from recurrent endocarditis after two years in the early- and late-onset groups, respectively, was 67.8 +/- 10.1% and 88.8 +/- 7.4% (p = 0.048). CONCLUSION: Clinical characteristics and outcomes differed significantly between early- and late-onset PVE. The clinical outcomes of patients with early PVE tend to be serious, and therefore stringent care should be taken to avoid contamination during the initial surgery and hence to reduce the incidence of the condition. PMID- 24224423 TI - Technique to treat extensive abscesses in double valve replacement for prosthetic valve endocarditis. AB - A 52-year-old man, who underwent double valve replacement for native valve infectious endocarditis, developed prosthetic valve endocarditis (PVE) at nine months after the initial operation. Operative findings revealed a wide aortic annular abscess, which extended through the intervalvular fibrous body to the mitral annulus. The infected mitral valve was excised through the atrial septum. After complete debridement of the abscess, a xenopericardial patch was sutured on to the abscessed area in the partially destroyed intervalvular fibrous body. Using this procedure, the affected annuli were reinforced and the abscessed area was isolated from the blood flow, reducing the probability of recurrent endocarditis. For valve implantation, 'anchoring' sutures were threaded externally through the aortic root, taking into consideration the fragility of the reconstructed annulus. The patient recovered with intensive administration of antibiotics and showed no sign of recurrent infection. The reinforcement of the intervalvular fibrous body and the use of 'anchoring' sutures may represent good alternatives for the surgical treatment of PVE. PMID- 24224424 TI - Surgical management of tricuspid valve endocarditis in systemically infected patients. AB - BACKGROUND AND AIM OF THE STUDY: Isolated bacterial tricuspid valve (TV) endocarditis is usually managed medically. Whilst the indications and optimal timing for surgical treatment of the condition have not been clearly defined, it is hypothesized that early surgery in patients who are bacteremic and/or have evidence of systemic seeding is superior to medical treatment. METHODS: All cases of isolated TV endocarditis reported between 2006 and 2011 at the authors' institution were reviewed. Patients with bacteremia and/or systemic seeding who were treated surgically after short-term medical therapy were compared to an equivalent group of patients who remained under long-term medical treatment only. RESULTS: A total of 45 patients with isolated TV endocarditis showed evidence of bacteremia and/or systemic seeding. Of these patients, 10 (22.2%) were treated surgically with valve repair or replacement, and 35 (77.8%) received long-term medical therapy only. The 30-day and one-year survival rates in both groups were comparable (100% versus 88.6%, p = 0.27). Patients treated surgically had clear blood cultures sooner (2.0 versus 6.7 days, p = 0.04), defervesced earlier (0 versus 9.0 days, p = 0.02), and demonstrated a complete resolution of TV vegetations (100% versus 30.0%, p = 0.003). Change in creatinine clearance (+22.1 versus +11.6 ml/min, p = 0.40) and durations of vasopressor support (6.8 versus 8.9 h, p = 0.86), mechanical ventilation (8.5 versus 32.2 h, p = 0.44), ICU stay (148.1 versus 53.8 h, p = 0.14) and total hospital stay (32.1 versus 24.6 days, p = 0.22) were not different between groups. Long-term echocardiogram surveillance demonstrated a higher prevalence of moderate-severe tricuspid regurgitation in the medically treated patients (75.0 versus 0.0%, p < 0.001). None of the patients treated surgically was readmitted with prosthetic valve endocarditis. CONCLUSION: Early surgery is warranted in patients with isolated TV endocarditis who are bacteremic and/or systemically infected despite optimal medical therapy. PMID- 24224425 TI - Valvular calcification, inflammation, and mortality in dialysis patients. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the correlates of valvular calcification (VC), including clinical and physiologic parameters, in individuals new to dialysis. In addition, the association of VC with coronary artery calcification (CAC) progression and mortality was investigated. METHODS: A total of 101 incident dialysis individuals underwent electrocardiogram-triggered multislice computed tomography (CT) to monitor the presence and quantification of calcification. The average follow up was 2.85 +/- 0.72 years. RESULTS: Twenty-six (25.7%) patients had only one valve calcified, while 10 (9.9%) had calcifications in both valves. Patients with VC were older, more likely to have a history of diabetes and/or cardiovascular disease (CVD), more likely to have CAC, and to be Caucasian; fibrinogen and interleukin-6 (IL-6) levels were also higher in these patients. Multivariable Poisson regression analysis revealed older age, history of CVD, increasing fibrinogen, and presence of CAC were independently associated with the presence of VC. Patients with VC also had a higher median annualized CAC progression compared to those without VC (2.90 versus 105.2, p = 0.004). The mortality rate per 100 years was 2.57 in patients without VC, compared to 4.20 and 13.76, respectively, for those with one or two calcified valves. An increasing number of calcified valves was associated with a higher mortality after adjustment for gender and race [HR 2.2 (1.03-4.69), p = 0.04], but was not statistically significant after adjustment for inflammatory markers such as IL-6 or fibrinogen. CONCLUSION: Traditional and novel risk factors are associated with the presence of VC, which is a risk marker for CAC progression and mortality in incident dialysis patients. PMID- 24224426 TI - Reoperation for non-structural valvular dysfunction caused by pannus ingrowth in aortic valve prosthesis. AB - BACKGROUND AND AIM OF THE STUDY: The authors' clinical experience is presented of non-structural valvular dysfunction of the prosthetic aortic valve caused by pannus ingrowth during the late postoperative period after previous heart valve surgery. METHODS: Between January 1999 and April 2012, at the authors' institution, a total of 33 patients underwent reoperation for increased mean pressure gradient of the prosthetic aortic valve. All patients were shown to have pannus ingrowth. The mean interval from the previous operation was 16.7 +/- 4.3 years, and the most common etiology for the previous aortic valve replacement (AVR) was rheumatic valve disease. The mean effective orifice area index (EOAI) of the previous prosthetic valve was 0.97 +/- 0.11 cm2/m2, and the mean pressure gradient on the aortic prosthesis before reoperation was 39.1 +/- 10.7 mmHg. RESULTS: Two patients (6.1%) died in-hospital, and late death occurred in six patients (18.2%). At the first operation, 30 patients underwent mitral or tricuspid valve surgery as a concomitant procedure. Among these operations, mitral valve replacement (MVR) was combined in 24 of all 26 patients with rheumatic valve disease. Four patients underwent pannus removal only while the prosthetic aortic valve was left in place. The mean EOAI after reoperation was significantly increased to 1.16 +/- 0.16 cm2/m2 (p < 0.001), and the mean pressure gradient was decreased to 11.9 +/- 1.9 mmHg (p < 0.001). CONCLUSION: Non structural valvular dysfunction caused by pannus ingrowth was shown in patients with a small EOAI of the prosthetic aortic valve and combined MVR for rheumatic disease. As reoperation for pannus overgrowth showed good clinical outcomes, an aggressive resection of pannus and repeated AVR should be considered in symptomatic patients to avoid the complications of other cardiac diseases. PMID- 24224427 TI - Diagnosis and surgical management of subaortic stenosis and mitral valve systolic anterior motion. AB - The case is reported of a patient with a previously undiagnosed cause of severe congestive heart failure (CHF) caused by the presence of a discrete subaortic stenosis (SAS) from a subvalvular membrane (SVM). The clinical decision making was complicated by the concurrent presence of systolic anterior motion (SAM) of the mitral valve leaflet. Due to the limitations and eventual failure of physiologically opposing medical management strategies, the patient eventually required an open-heart surgical approach and underwent intraoperative SVM resection. A persistent intraoperative left ventricular outflow tract (LVOT) gradient of 50 mmHg due to SAM prompted mitral valve replacement, which resulted in a complete resolution of the LVOT gradient and symptoms. In this extremely rare scenario of SAS and SAM, when SVM resection is thought to be inadequate to relieve LVOT obstruction due to the concurrent presence of SAM, mitral valve replacement represents a reasonable therapeutic approach. PMID- 24224428 TI - Mechanical heart valve thrombosis in pregnancy. AB - Effective anticoagulation is critical in patients with mechanical prosthetic heart valve (MPHV), but remains challenging in pregnancy because both oral anticoagulation and heparins are associated with important fetal and maternal risks. A 33-year-old high-risk pregnant woman presented with MPHV thrombosis during early pregnancy. Resolution of the thrombus and eventual resumption of normal prosthetic mitral valve function was obtained through treatment with low molecular weight heparin (LMWH). This case of early pregnancy MPHV thrombosis emphasized the importance of adequate initial coagulation prior to pregnancy and the potential need to extend measurements to both peak and trough levels to assure an adequate level of anticoagulation in women with MPHV treated with LMWH during pregnancy. PMID- 24224429 TI - Renal cell carcinoma with extensive cavoatrial involvement. PMID- 24224430 TI - The principles of abdominal wound closure. AB - BACKGROUND: Incisional hernia (IH) is a common complication of abdominal surgery. Its incidence has been reported as high as 39.9%. Many factors influence IH rates. Of these, surgical technique is the only factor directly controlled by the surgeon. There is much evidence in the literature on the optimal midline laparotomy closure technique. Despite the high level of evidence, this optimal closure technique has not met wide acceptance in the surgical community. In preparation of a clinical trial, the PRINCIPLES trial, a literature review was conducted to find the best evidence based technique for abdominal wall closure after midline laparotomy. METHODS: An Embase search was performed. Articles describing closure of the fascia after midline laparotomy by different suture techniques and/or suture materials were selected. RESULTS: Fifteen studies were identified, including five meta-analyses. Analysis of the literature showed significant lower IH rates with single layer closure, using a continuous technique with slowly absorbable suture material. No significant difference in IH incidence was found comparing slowly absorbable and non absorbable sutures. Furthermore, a suture length to wound length ratio of four or more and short stitch length significantly decreased IH rates. CONCLUSIONS: Careful analysis of the literature indicates that an evidenced based optimal midline laparotomy closure technique can be identified. This technique involves single layer closure with a running suture, using a slowly absorbable suture with a suture length to wound length ratio of four or more and a short stitch length. We adopt this technique as the PRINCIPLES technique. PMID- 24224431 TI - Transanal endoscopic microsurgery for rectal tumours using a Single Incision Laparoscopic Port. AB - BACKGROUND: Transanal endoscopic microsurgery (TEM), first described by Buess enables a less aggressive approach of benign rectal lesions, or even early rectal cancer in a curative intent. MATERIALS AND METHODS: The SILS Port, initially designed for laparoscopic surgery, was successfully used for 20 TEM procedures in 16 patients. Local resection was sufficient in 15 procedures (benign tumours or pT1) out of 20, whereas 5 TEM operations required additional surgery: 3 rectal resections (pT1Nx, pT1sm3Nx and pT2N1) and 1 TEM revision (1 patient refused the rectal resection (pT1Nx). Postoperative complications following Dindo-Clavien were: grade II in 4 patients (pain: 2; fever: 1; bleeding: 1) and grade IIIb in 2 patients (bleeding). No long-term faecal incontinence was noted. CONCLUSION: TEM using the SILS Port is a safe and effective procedure for local resection of benign and certain malignant tumours. Using such a cheaper device, TEM procedure could be available in any operating theatre. PMID- 24224432 TI - Value of preoperative esophagogastroduodenoscopy in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: Roux-en-Y gastric bypass hinders post-operative endoscopic evaluation of the upper gastrointestinal tract. Our aims were to determine the prevalence of preoperative endoscopic findings in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) and to determine the proportion of patients in which these findings changed surgical management. METHODS: We retrospectively evaluated electronic medical records of patients undergoing esophagogastroduodenoscopy (EGD) with routine antral biopsy for Helicobacter pylori (HP) detection, prior to LRYGB between January 2003 and January 2010 at our institution. The prevalence of all endoscopic findings was determined. RESULTS: 652 underwent preoperative endoscopy prior to LRYGB. The mean age was 39.5 +/- 11.3 years and mean body mass index was 42.8 +/- 5.0 kg/m2. Abnormalities were found in 444 patients (68.1%). Findings at EGD were hiatal hernia 24.3% (n = 159), esophagitis 30.8% (n = 201), Barrett's esophagus 0.8% (n = 5), gastritis 36.2% (n = 236), gastric or duodenal ulcers 7.5% (n = 69) and 2 cases of gastric cancer. The prevalence of HP infection was 17.6% (n = 115). In 51 patients (7.8%), endoscopic findings led to postponement of surgery: in 49 patients, gastric or duodenal ulcer had to be treated prior to surgery, in 2 patients, gastric cancer led to changement in surgical approach. CONCLUSIONS: Routine preoperative EGD detects different abnormalities which need a specific approach prior to bariatric surgery. EGD with routine biopsies for HP detection should be included in the preoperative workup prior to LRYGB. Positive EGD findings led to a change in medical treatment in a quarter (24.3%) of patients. Postponement of surgery due to the EGD findings was less frequent (7.8%). PMID- 24224433 TI - Previous bariatric surgery increases postoperative morbidity after sleeve gastrectomy for morbid obesity. AB - OBJECTIVES: Sleeve gastrectomy (SG) has been used as the first step of a staged malabsorptive procedure for high-risk patients. More recently SG was proposed as an stand alone procedure in the treatment of morbidly obese patients. The aim of this study is to analyze perioperative outcome of morbid obese patients after SG. METHODS: 301 patients, 201 women and 100 men, undergoing SG were retrospectively analyzed. SG was performed by 17 surgeons all member of the Club Coelio. The mean BMI was 44.7kg/m2 (27.4-70.3 kg/m2). 34 patients (11.3%) of our series had SG as revisional surgery. These revisional procedures consisted of 32 conversions from gastric banding, 1 conversion from vertical gastroplasty (VBG) and 1 from transoral endoscopic gastroplasty. Among the 32 patients that had revisional SG after a gastric banding, 13 bands were removed at least 3 months before the revisional SG and 19 bands were removed during the SG procedure. Endpoints were perioperative morbidity and mortality and potential risk factors for complications, mainly per or postoperative bleeding or leakage. RESULTS: Overall mortality was 0% and morbidity was 10.3%. Perioperative bleeding occurred in 10 patients (3.3%), leakage in 12 patients (4%) patients and stenosis in 3 patients (1%). The risk of leakage was significantly higher after revisional bariatric surgery and in case of gastric perforation during surgery (p = 0.0001). Previous gastric banding is also associated with a higher risk of postoperative bleeding (p = 0.0006). CONCLUSIONS: SG can be safely performed but patients and surgeons must be aware of a higher risk of postoperative complications when SG is proposed as a revisional surgery. PMID- 24224434 TI - Carinal sleeve pneumonectomy for lung cancer. AB - BACKGROUND: Here, we present our experience of 12 lung cancer cases operated with carinal sleeve pneumonectomy (CSP) from 2001 to 2011. METHODS: 12 cases who had undergone CSP in our department from 2001 to 2011 were retrospectively evaluated and presented by taking into account their demographical and clinical features, the surgical technique that was used, the complications that developed and the latest conditions of these patients. RESULTS: Of the 12 cases, 11 were male and 1 was female with a mean age of 58.6 years (40-71 years). 11 cases had right and 1 had left CSP. The ethiology for resection was lung cancer in all cases. 10 cases had carinal invasion of the lung cancer, 1 had bronchopleural fistula developing after right pneumonectomy, 1 had distal tracheal rupture due to intubation tube placed during pneumonectomy; these all resulted in performing CSP. Five patients developed complications during the postoperative period. Three cases developed recurrences/metastases during the follow-up. Nine patients died, 3 patients were alive and were followed-up by our department. For all the cases, the median survival was 9 months, the estimated survival rate of 2-years was 33%, and 5-year survival rate was 22%. Survival for 2-4 years was 71%. CONCLUSIONS: We think that with increasing surgical experience better results are obtained in these technically demanding procedures. PMID- 24224435 TI - Clinical significance of the expression of alpha-methylacyl-CoA racemase in squamous cell carcinoma and adenocarcinoma of the lung. AB - BACKGROUND: The role of alpha-methylacyl-CoA racemase (AMACR) in pathogenesis and diagnosis of different types of cancer has been investigated during last decade. This study is conducted to investigate AMACR expression in adenocarcinoma and squamous cell carcinoma (SCC) of lung and its correlation with clinical characteristics and survival. METHODS: The clinicopathologic characteristics of 146 patients who underwent a potentially curative surgical resection between June 2000-2009 in our clinic were reviewed retrospectively. The patients who were given adjuvant chemotherapy and/or radiotherapy, with an evidence of residual tumor at resection margin and who died due to postoperative mortality and due to reasons not related to lung cancer were excluded. Data from remaining 67 patients were analyzed for survival. For the correlation between progression and AMACR immunoreactivity, data from 62 patients who had postoperative follow up in our center were analyzed. RESULTS: AMACR immunoreactivity was observed more frequently in adenocarcinoma group than SCC group (p = 0,046). The samples with invasive adenocarcinoma--lepidic predominant pattern also showed high rates of positive staining (73%). We could not show a statistically significant correlation between AMACR immunostaining and degree of differentiation, age, gender, pathologic T status, N status, or stage. We failed to show a statistically meaningful effect of AMACR on overall and progression-free survival. CONCLUSION: Adenocarcinoma had higher rates of positive immunostaining for AMACR than SCC (p = 0,046). But the presence of AMACR expression did not have a statistically meaningful effect on overall and progression-free survival in adenocarcinoma and SCC of lung. PMID- 24224436 TI - The use of single incision thoracoscopic pleurectomy in the management of malignant pleural effusion. AB - BACKGROUND: A number of procedures have been used in the management of malignant pleural effusion including repeated thoracentesis, tube thoracostomy, drainage with catheter, chemical pleurodesis, pleurectomy and pleuro-peritoneal shunt. However, the optimal method of management remains unclear. On the other hand, single incision thoracoscopic surgery has been defined as a less invasive method than the standard threeportal videothoracoscopy. We herein present our series of patients who underwent single incision thoracoscopic pleurectomy for malignant pleural effusion. PATIENTS AND METHODS: We performed a single incision thoracoscopic pleurectomy in a total of 19 consecutive patients, 11 (57.8%) male and 8 (42.2%) female with a mean age of 56.3 +/- 16.9 years who had malignant pleural effusions. We made a single 2-2.5 cm incision at the seventh or eighth intercostal spaces on the midaxillary line for the procedure. RESULTS: We performed a total of 23 single incision thoracoscopic total pleurectomies consisting of 11 (57.8%) right-sided, 4 (21.1%) left-sided and 4 (21.1%) bilateral procedures. The mean total postoperative drainage was 553 +/- 266 cc (Median; 470 cc), and the mean chest tube removal time was 2.3 +/- 0.4 days (Median; 2 days). We observed neither morbidity nor mortality. No patient required an additional port or a conversion to thoracotomy. Median follow-up was 83 days (range, 30 to 359 days). Pleural effusion recurred in two (8.6%) out of 23 procedures which resulted in a success rate as 91.4% for the procedure. CONCLUSION: Single incision thoracoscopic pleurectomy is a safe, less invasive and an effective method of pleurodesis with a low recurrence rate in patients with malignant pleural effusion. PMID- 24224437 TI - Penetrating cardiac injuries in Belgium: 20 years of experience in university hospitals in Brussels. AB - BACKGROUND: Cardiac wounds remain as highly lethal lesions in which their prognosis depends on the emergency management. OBJECTIVES: The aim of this study is to analyse experiences of cardiac surgeons in different hospitals in Brussels and compare it with the findings in the literature. METHODS: From 1st January 1990 till 1st December 2010, all penetrating cardiac wounds in three Brussels hospitals were retrospectively reviewed. Data recorded included clinical parameters, surgical constatation and outcome. RESULTS: A total of fourteen (12 male/2 female) patients sustained penetrating cardiac injuries. There were thirteen patients (93%) with stabs wounds and, one patient (7%) with gunshot wound. Wound locations are as follows: ten patients (71%) right ventricle, three patients (22%) the pericardium, and one patient (7%) the left ventricle. The hemodynamic status was unstable in nine patients (64%), in-extremis in two patients (14%) and stable in three patients (22%). The mean Abbreviate Injury Score was 4.6 and the mean New Injury Severity Score was 31. Thirteen patients (93%) had operations (11 sternotomie, 2 thoracotomies). Two patients required cardiopulmonary bypass. Three patients (22%) died. CONCLUSION: Penetrating cardiac wounds are relatively rare in Belgium, which is mainly due to stabs and with consequent mortality. The implementation of clear guidelines is necessary to improve survival. PMID- 24224438 TI - Sliding hernias in female children. AB - INTRODUCTION: Articles published in the English language report that 15-20% of the inguinal hernias in female children are sliding hernias. These studies do not specify the age at moment of surgery, neither the age distribution of sliding hernia. We retrospectively evaluated inguinal canal pathologies to answer these questions. MATERIAL AND METHOD: We retrospectively evaluated the records of the patients operated on at the Pediatric Surgery Clinics of the Ordu, Usak and Denizli State Hospitals and the Afyon Obstetrics and Gynecology Hospital. RESULTS: A total of 3105 cases had been operated on for an inguinal hernia between January 2008 and December 2010 and 673 (21.6%) were female. The most common age at surgery was between 0 and 1 years (26.5%). A sliding hernia was found in 22.4% (n = 151) of all cases. The sliding hernia rate was 45.8 (n = 82) and 14.9% (n = 69) in children younger and older than 1 year of age respectively (p < 0.05). The most frequently sliding organ in both groups was the ovary, followed by the fallopian tubes. CONCLUSION: A sliding hernia is more common in female children under the age of 1 year and surgical treatment should be planned within a short period once the diagnosis is made. In addition, this recent statistical value for subjects aged 0 to 1 year and over 1 year can be used in new clinical studies. PMID- 24224439 TI - The protective effect of ellagic acid on lung damage caused by experimental obstructive jaundice model. AB - AIM: This study aimed to investigate protective effects of ellagic acid on lungs in an experimental obstructive jaundice model. METHODS: Four groups were established, each consisting of ten randomly selected rats: Group 1: sham, Group 2: ellagic acid, Group 3: obstructive jaundice, and Group 4: obstructive jaundice + ellagic acid. Ellagic acid was administered orally at a dose of 60 mg/kg/day to group 2 and 4. The animals were sacrificed eight days later. The total oxidative status and the total antioxidant capacity in their lung tissue were determined, and malondialdehyde levels in their blood were measured. Histopathological changes in the lungs were examined. RESULTS: In the obstructive jaundice group treated with ellagic acid, there was a decrease in malondialdehyde levels and a reduction in the total oxidative status and the oxidative stress index, whereas the total antioxidant capacity increased (p < 0.001). The histopathological examination showed that neutrophil leukocyte infiltration and edema formation decreased and destruction of lung parenchyma disappeared following the treatment with the ellagic acid (p < 0.05). CONCLUSION: This study shows that ellagic acid has a protective effect against oxidative damage in lung tissue in obstructive jaundice. PMID- 24224440 TI - Acute chest pain while exercising: a case report of Bochdalek hernia in an adolescent. AB - We present the case of a 17-year old male patient with a symptomatic congenital posterolateral diaphragmatic hernia with acute onset of symptoms. He was admitted to our emergency department a few days after the onset of symptoms. A large thoracic herniation on the left side was seen on chest X-ray. Further investigation by computed tomography showed the presence of stomach, spleen and colon in the herniation. Semi-urgent surgery was performed by a laparoscopic approach. The diaphragmatic defect was closed with interrupted sutures. The operation and postoperative recovery were uneventful. PMID- 24224441 TI - Handlebar hernia: an uncommon cause of intra-abdominal lesions. AB - A traumatic abdominal wall hernia (TAWH) is an uncommon complication of abdominal trauma. Handlebar hernia is an even rarer type of traumatic abdominal wall hernia, with only 33 previously reported cases in literature. It is caused by a local trauma with a handlebar-like object which is not sharp enough to penetrate the elastic skin, but has sufficient focused force to breach the muscle and fascia of the abdominal wall. A high index of clinical suspicion for associated intra-abdominal lesions in patients with traumatic abdominal wall hernia is warranted. This may not only influence the immediate treatment of the abdominal hernia but also the type and timing of mesh repair to be performed. Early repair is mandatory to avoid complications. The choice for primary repair versus mesh repair will be discussed according to the size of the hernia and the amount of tissue destruction by the trauma. The type of mesh used for the repair will be determined by presence or absence of contamination in the abdomen. PMID- 24224442 TI - Presacral ganglioneuroma with abnormal FDG uptake: a case report. AB - Ganglioneuromas are rare, benign, well-differentiated, slowgrowing tumors of the sympathetic nervous system, composed of large, mature neurons in a stroma composed of Schwann cells. Ganglioneuromas are derived from the neural crest cells and can arise anywhere from the base of the skull to the pelvis. The pre sacral area is a very rare location for ganglioneuromas to develop. We describe the case of a 31 year old woman, who was incidentally found to have an abnormal pre-sacral mass. The following work-up, revealed the mass to be growing on imagery (computed tomography and magnetic resonance imagery) and fluorine-18 fluorodeoxiglucose avid. The mass was removed by assisted laparoscopy and was found to be a benign ganglioneuroma. This is the first described case of fluorine 18 fluorodeoxiglucose avid, pre-sacral, benign ganglioneuroma. PMID- 24224443 TI - Rectal duplication: a case report. AB - Gastrointestinal tract duplications are uncommon congenital abnormalities, that may occur anywhere along the alimentary tract. Most frequently they occur at the level of the small bowel tract and are symptomatic before the age of two. In our case we report the history of a 68-years old women with a colon duplication, especially a rectal duplication. This is very exceptional. PMID- 24224444 TI - Desmoid tumour of the breast: case report and review of the literature. AB - Fibromatosis or desmoid tumour of the breast is an extremely rare, locally aggressive tumour with a tendency to relapse. Nevertheless these tumours do not have metastatic potential. Early recognition and wide local excision of the tumour is the treatment of choice. We present a case of a desmoid tumour of the breast in a 67-year-old woman and provide a review of the literature. PMID- 24224445 TI - Reconstruction of a common bile duct injury by venous bypass. AB - Hepaticojejunostomy is the standard technique for the reconstruction of severe iatrogenic lesions of the common bile duct (CBD), although the technique itself is major surgery with a complication rate up to 30%. We report a case of a male patient with a iatrogenic complete transsection of the CBD. Due to multiple previous operations and the present inflammation a standard reconstruction technique was not possible to perform. A neo-bile duct was created using a segment of the Great Saphenous Vein (GSV) synchronously with an external biliary drainage by PTCA and biliary stenting (after 4 weeks). The stent was removed 8 months later. Cholangiography showed normal bile flow without occlusion. Blood tests normalised. We believe that using an autologous vein graft in combination with a removable or biodegradable stent is the right track for the reconstruction of the CBD in the future. PMID- 24224446 TI - Single-incision laparoscopic cholecystectomy: a new retraction technique. AB - BACKGROUND: Laparo-endoscopic single site cholecystectomy receives great interest from the surgical community. It has potential for reducing postoperative pain, length of hospital stay and improving cosmesis. Minimally invasive surgeons have been forced to develop techniques for providing adequate retraction of the gallbladder. Herein, we describe a new retraction technique to improve the dissection of Calot's triangle. SURGICAL TECHNIQUE: Twelve patients underwent laparo-endoscopic single site laparoscopic cholecystectomy using this retraction technique. An intra-umbilical skin incision was made by pulling out the umbilicus. A SILS port was placed through an open approach. We inserted a 10-mm 30 degrees camera through the SILS port without using any trocar. One suture was knotted in the middle of the gallbladder. Gallbladder retraction was achieved by the use of an EndoClose needle that was inserted into abdominal cavity at the subcostal border. The floppy knot was held by the notched end of the EndoClose needle. This device provided retraction of the gallbladder in every direction. CONCLUSIONS: Adequate retraction greatly simplifies laparo-endoscopic single site cholecystectomy. New retraction techniques will enable wider use of this novel minimally invasive approach. Further work is needed to investigate the advantages of this new technique. PMID- 24224447 TI - [Islet transplantation as a treatment for complications of type I diabetes]. AB - Reduced physical activity and high calories up-take along with carbohydrates based diet are considered to be a leading cause of diabetes mellitus rise in western countries. Together with rise in DM morbidity, increase of complicated diabetes is also observed. Pancreas transplantation occurred to be a milestone in diabetic patient management. Guine pig pancreatic islets isolation performed for the first time by Moskalewski in 1965 and updates of his method have given an opportunity to introduce allogenic isolated islets transplantation to clinical usage. For the first time in Poland clinical allotransplantation of isolated pancreatic islets took place in Department of General Surgery and Transplantology of Medical University of Warsaw in 12's June 2008. Unfortunately, unsatisfying results of islet transplantation, specially short period of insulin independence after successful transplantation related with multifactor islet function lost, reduce clinical indications. In this publication we have analyzed known and potential factors of islet lost and we have tried to find way to prevent them, with a long period insulin-independence after transplantation as a main goal. PMID- 24224448 TI - [The effect of coffee on blood pressure at healthy subjects]. AB - Coffee is one of the most popular beverages. Its stimulatory effects comes from the natural alkaloid- caffeine. Caffeine is the antagonist of the adenosine receptors A1 and A2. Caffeine acts chronotropic positive and increases heart action; inotropic positive and increases cardiac contraction; tronotropic positive and increases hearts muscular ton, brain's vascular stenosis, vasodilatation of coronal vessels, renal vessels, muscular vessels and skin vessels. The aim of the study was determination of coffee effect on blood pressure in healthy subjects. MATERIAL AND METHODS: 17 healthy subjects (age 22 44 years; median 22 years) was included. There were two experiments. Experiment 1: examined persons drank instant coffee with or without caffeine. Experiment 2: examined persons drank natural coffee with or without caffeine. The blood pressure and pulse were examined before coffee drinking and 15 and 30 minutes after (in experiment 1) and only 30 minutes after (in experiment 2). RESULTS: The blood pressure was increased on 10 mmHg or more in 9-40% of examined subjects in all groups, but there were no significant difference between groups. The pulse increased (10 or more per minute) was observed only in one person and decrease was observed in three who drank natural coffee with caffeine. CONCLUSIONS: In healthy subjects the blood pressure does not increased significantly after caffeine consumption. The consumption of caffeine in large doses may be harmful to some hypertensive or hypertension-prone subjects. PMID- 24224449 TI - [The impact of ascorbic acid on the concentrations of antioxidative vitamins in the plasma of patients with non-small cell lung cancer undergoing first-line chemotherapy]. AB - One of the main after-effects of chemotherapy used in cancer treatment is an augmented production of reactive oxygen species (ROS). In turn ROS become a source of unwanted side effects of chemotherapy, often forcing the discontinuation of the therapy. Ascorbic acid (vitamin C), being an antioxidant, can strengthen the antioxidative barrier of an organism. The aim of the study was an assessment of the concentrations of A, C and E vitamins in the plasma of NSCLC patients undergoing chemotherapy supplemented with vitamin C. MATERIAL AND METHODS: 25 first-line chemotherapy patients with inoperable NSCLC, including 19 men and 6 women aged between 37-73 years (average age 60.1 +/- 8.8 years) have undergone the examination. Their chemotherapy has been supplemented with ascorbic acid (vitamin C dose of 600 mg per 24 hours). Control group consisted of 24 healthy individuals, including 18 men and 6 women aged between 49-71 years (average age 59.5 +/- 6.6 years). In cancer patients the concentration of A, C and E vitamins was assessed by spectrophotometry using T60V spectrophotometer (PG Instruments) before and after first-line chemotherapy which was supplemented with vitamin C. In control group the concentrations of antioxidative vitamins was assessed only once. RESULTS: In comparison to the control group the concentrations of the A, C and E vitamins in the plasma of NSCLC patients was significantly lower (p < 0.05). After 6 weeks of chemotherapy supplemented with vitamin C a significant rise of concentrations (p < 0.05) of all the vitamins tested for was observed. The biggest rise was noted for vitamin C (99.8%). CONCLUSIONS: The supplementation of the chemotherapy of NSCLC patients with C vitamin leads to rise of the low concentrations of A, C and E vitamins in the plasma. This suggests strengthening of the antioxidative barrier in patients. PMID- 24224450 TI - [The clinical significance of GastroPanel in diagnostics of Helicobacter pylori eradication efficiency in patients with dyspepsia with correlation of family history of gastric cancer]. AB - Gastric cancer remains a significant medical and social problem. Familial, hereditary, social, and demographic factors increase the susceptibility of subjects to cancer development, especially those infected with Helicobacter pylori (H. pylori). Apart from genetic studies, there are ongoing biochemical studies of possible practical value in assessment of the risk of gastric cancer development. The GastroPanelBiohit test, that include determination of the levels of gastrin (G-17), pepsinogen I (PGI), pepsinogen II (PGII) and antibodies IgG/IgA against H. pylori in serum, allowed us to determine whether there are any abnormal changes in the gastric mucosa. The aim of the study was to determine whether GastroPanel parameters, identified in patients with dyspeptic symptoms (with or without history of gastric cancer in first degree relatives) before and after successful eradication of H. pylori, have any clinical value, especially in gastric cancer development. MATERIAL AND METHODS: The study comprised 61 patients aged 18-56 years with symptoms of dyspepsia. In all patients, the preliminary urea breath test (UBT) for the presence of H. pylori was performed and the positive result qualified for further study. For final analysis, 42 patients were approved, who were divided into two groups: group I (a control group) - 22 patients with negative family history of gastric cancer among the relatives of first degree, group II - 20 patients with positive history of gastric cancer among the relatives of first degree. All the patients had the gastroscopy with the biopsy of gastric mucosa for the histopathological evaluation. Additionally, the GastroPanel test was performed. RESULTS: In the blood serum of the patients with H. pylori infection, the concentrations of gastrin (G-17), pepsinogen I (PGI) and pepsinogen II (PGII) did not depend on family history of gastric cancer (p > 0.05). Successful eradication of H. pylori decreases the levels of G-17, PGI and PGII (statistical significance p < 0.05), and this correlates with the histopathological changes of gastric mucosa. The patients with positive family history of gastric cancer had more intense H. pylori colonization of gastric mucosa (IV degree of insensitivity of infection in UBT; group I - 22% vs group II - 69%) as compared to the control group. After effective eradication of H. pylori, statistically significant decreases of IgG H. pylori antibodies and of the level of gastrin (p < 0.05) in blood serum were seen (in a 3 months follow up) only in the control group. CONCLUSIONS: Independently of the history of familial gastric cancer, the GastroPanelBiohit test provides important clinical data useful for diagnosis, for assessment of effectiveness of H. pylori eradication therapy and in evaluation of the degree of the inflammatory changes in gastric mucosa. PMID- 24224451 TI - [The diagnostic value of non-invasive biochemical biomarkers in alcohol abuse]. AB - The diagnosis of alcoholic liver disease, steatosis, fibrosis and alcoholic steatohepatitis, can be evaluated by means of non-invasive biochemical biomarkers: SteatoTest, FibroTest and AshTest. The aim of the study was to evaluate the diagnostic usefulness of these tests for the detection of steatosis, fibrosis and alcoholic steatohepatitis in alcohol abusing patients. MATERIAL AND METHODS: The experimental group comprised 137 alcohol-dependent subjects. The control group was consisted of 50 healthy social drinkers. Ten biochemical assays were determined according to methods recommended by the provider of the tests - BioPredictive company. The scores were computed by the company according to the bilateral agreement. RESULTS: The diagnostic sensitivity and specificity were as follows: 61.9% and 93.9% for SteatoTest, 61.3% and 93.9% for FibroTest and 9.6% and 93.9% forAsh Test. The diagnostic power of Steato Test (A UC = 0.806) and FibroTest (AUC = 0.795) were significantly higher than the diagnostic power of AshTest (AUC = 0.626) but did not differ from each other. The probability of a positive test results of Steato Test and FibroTest is 10-times more likely in alcoholics than in healthy individuals. CONCLUSION: SteatoTest and FibroTest can be useful diagnostic tool for the detection of liver steatosis and fibrosis in alcohol-dependent patients but cannot differentiate of these clinical conditions. PMID- 24224452 TI - [Influence of naloxone on uterine contractions in patients with primary dysmenorrhea]. AB - Dysmenorrhea is a common condition among women in childbearing age. An increased uterine contractions, resulting among others from increased vasopressin and oxitocin secretion, is considered as a main cause of the primary dysmenorrhea. The endogenous opioids play the important role in the control of oxytocin and vasopressin release from the pituitary gland. Naloxone is a selective opioid receptor antagonis. So far, there is not much data on naloxone effect on uterine contractions. The aim of study was to determine the influence of naloxone on uterine contractions in patients with primary dysmenorrhea. MATERIAL AND METHODS: There were 10 female patients with primary dysmenorrhea included into the study. The uterine contractions had been recorded for 30 minutes before and 2 hours after injection of naloxone at the first day of menstruation. RESULTS: The intrauterine pressure recordings revealed a severe spontaneous uterine contractions, with high frequency and amplitude, at the time of dysmenorrhea. An intravenous administration of naloxone decreased uterine contractile activity and pain intensity. CONCLUSIONS: Naloxone acting on central nervous system decreases the uterus contractions in the patients suffering from dysmenorrhea. Unexplained mechanisms and multiple factors involved in the pathogenesis of primary dysmenorrhea indicates a need for the further studies on this subject. PMID- 24224453 TI - [Surgical problems of homeless people]. AB - Estimated quantity of homeless people in Poland is about 30.000. Health conditions of homeless depends on poor living conditions, alcohol abuse and lack of medical care. The aim of the study was to present surgical problems of homeless people at St. Brother Albert's Aid Society Shelter in Szczodre. MATERIAL AND METHODS: In years 2009-2011 in St. Brother Albert's Aid Society Shelter in Szczodre 1053 homeless were provided outpatient surgical care. The frequency of occurrence of diseases rated on the basis of the medical examination, medical history and medical records. RESULTS: The patients were aged 20-82 years (median: 46 years). The most common surgical problem of homeless people was skin infectious such as scabies, lice, tinea and lower limb ulceration due to underlying chronic vanous insufficiency or due to sustained injury. Other problems requiering surgical care were: frostbite, abscesses, phlegmon, unhealed wounds, back pain and pain due to sustained injuries. Most frequent causes of homelessness were family problems, alcohol abuse, conflict with the law, loss of ocupation or loss of home. CONCLUSIONS: Surgical diseases of homeless people have multifactorial etiology. The most frequent diseases in our patients were skin infectious and lower limb ulcerations. Medical care oriented on specific needs of homeless people is particulary important because poor health condition is not only consequence but could also be the cause of homelessness. PMID- 24224454 TI - [Validation of the Polish version of The Authentic Leadership Questionnaire for the of evaluation purpose of nursing management staff in national hospital wards]. AB - The Authentic Leadership Questionnaire (ALQ) is a standardized research instrument for the evaluation of individual elements of leader's conduct which contribute to the authentic leadership. The application of this questionnaire in Polish conditions required to carry out the validation process. The aim of the study was to evaluate of validity and reliability of the Polish version of the American research instrument for the needs of evaluation of authenticity of leadership of the nursing management in Polish hospitals. MATERIAL AND METHODS: The study covered 286 nurses (143 head nurses and 143 of their subordinates) employed in 45 hospitals in Poland. Theoretical validity of the instrument was evaluated using Fisher's transformation (r-Person correlation coefficient), while the criterion validity of the ALQ was evaluated using rho-Spearman correlation coefficient and the BOHIPSZO questionnaire. The reliability of the ALQ was assessed by means of the Cronbach-alpha coefficient. RESULTS: The ALQ questionnaire applied for the evaluation of authenticity of leadership of the nursing management in Polish hospital wards shows an acceptable theoretical and criterion validity and reliability (Cronbach-alpha coefficient 0.80). CONCLUSIONS: The Polish version of the ALQ is valid and reliable, and may be applied in studies concerning the evaluation of authenticity of leadership of the nursing management in Polish hospital wards. PMID- 24224455 TI - [Elafin and its influence on the patomechanism of preterm labor]. AB - The prevention of infection in pregnancy is critical to provide an appropriate fetal development and term delivery. Natural antimicrobials are the mediators of innate immune system with antibacterial, anti-viral and anti-fungal properties. It has been found that these antimicrobials play the great role in a homeostasis of bronchial and intestine epithelium, endometrium and epidermis. The activity of elafin--neutrophil elastase inhibitor--has been found in female reproductive system microenvironment (cervix, endometrium and fallopian tube) with the highest expression in the endometrium of non-pregnant women during ovulation and menstruation. The influence of elafin has been established on the maintenance of early pregnancy and the patomechanism of preterm labor and other pathology of pregnancy. Elafin level in amniotic fluid has been confirmed to be decreased in cases of preterm rupture of membranes (PROM). The protein may be a good marker of preterm labor and use in its diagnostics and treatment. PMID- 24224456 TI - [Mesothelin in ovarian cancer]. AB - Ovarian cancer is a neoplasm with high mortality rate. Its progression is mostly asymptomatic, which results in its first diagnosis in a late stage of the disease. Currently there are no reliable diagnostic methods for early detection of ovarian cancer. Molecular mechanisms leading to its development are not yet fully discovered. Recent studies show that mesothelin gene is up-regulated in patients with serous ovarian cancer. Mesothelin is a glycoprotein found in cell membranes of mesothelial cells lining the peritoneum, pericardium and pleura. Association of mesothelin in the development of ascites, intraperitoneal spread of the neoplasm, and its capability to modulate immune response have been show. It has been found that patients diagnosed with ovarian cancer have elevated serum mesothelin specific IgG levels. Mesothelin is also able to induce a cellular immune response, which is used in researches of ovarian cancer vaccines. High mesothelin expression in cancer tissues and its regular low expression in physiologic ones makes the glycoprotein a worthy candidate for the purpose of ovarian cancer treatment. Current studies assess the use of mesothelin as a target antigen as well as its immunogenicity. The methods of treatment include the use of recombined immunotoxin synthesized from the Pseudomonas exotoxin A (SSIP), MORAb-009 - chimeric monoclonal antibody, immunoconjugates (antibody - drug conjugates), cancer vaccines and gene therapy. The results of these studies are promising but further trials in larger population are required to confirm this. PMID- 24224457 TI - [The psychological and social support in patients with psoriasis]. AB - The meaning of non medical forms of support in the treatment of psoriasis is discussed in the paper. Related with psoriasis negative self image and feeling of stigmatization cause various mental disorders. Stress, depression, mental condition affect the appearance of psoriasis. Because of numerous studies and identify the factors and relationships important for psoriasis, patients can take the appropriate psychological and social support. Relaxation techniques, cognitive-behavioral therapy and support groups have a positive effect on the treatment of psoriasis. They reduce the level of stress in the patient, learn emotional control, adequate self-esteem, which leads to the acceptance of the disease and improve the quality of life of the patient. PMID- 24224458 TI - [The use of transdermal therapeutic systems in physical therapy]. AB - Methods of the transdermal administration of drugs have long been sought in the medical field in order to ensure the noninvasive and painless transmission of the medicine. Such methods include the TTS (transdermal therapeutic system). It is a method, or rather a set of methods that allows the introduction of the drug to the sites of pathologically changed areas without the pharmacological burdening of the whole body. An important aspect of this treatment is that the substance can be introduced passively (even to unconscious or sanity-limited patients) or actively, i.e. exactly at the point of the pathological changes, thus avoiding contraindications for applications in the general purpose and discomfort of the patient. The transdermal therapeutic system can be found in various areas of medicine. It is also increasingly beginning to act as an alternative to a number of other areas such as pharmacotherapy, physical therapy, and cosmetology; as a precognitive application, hormonal substitution, nutritious, analgesic, anti inflammatory, or anti-swelling application; an application for the treatment of scars, delayed fracture healing, the neuromuscular stimulation, trophy of tissues; or a bacteriostatic application. Further research in this area seems to have a great practical significance. PMID- 24224459 TI - [Old age--neither sour nor bitter]. AB - The development of medicine involves prolongation of human life. In many cases, however, chronic diseases, quite common in the elderly, make the quality of life very poor. We put the question: why we--the doctors--are not able to cope with the problem and whether the pharmacological treatment actually helps? A common medical practice is the use of proton pump inhibitors for various, often nonspecific disorders of the gastrointestinal tract. Statistics point to the overuse of the drugs from this group, also in the elderly. Despite the belief in the safety of such proceedings, proton pump inhibitors may pose a significant threat to older patients contributing to the symptoms worsening, and significantly affecting the mechanisms of acid-base balance. Inhibition of gastric acid secretion in the stomach is not a golden receipt in the case of dyspeptic symptoms, especially in people with the elderly. In many of them achlorhydria or hipochlorhydria is diagnosed. In others, such treatment, may not bring an expected relief in symptoms, while contributing to disturbances of acid base balance, and--indirectly--have an adverse effect on renal function. We suggest moderation in the use of proton pump inhibitors to bring patients to a real, and not quasi wellness. PMID- 24224460 TI - In situ electrode calibration strategy for voltammetric measurements in vivo. AB - Technological advances have allowed background-subtracted fast-scan cyclic voltammetry to emerge as a powerful tool for monitoring molecular fluctuations in living brain tissue; however, there has been little progress to date in advancing electrode calibration procedures. Variability in the performance of these handmade electrodes renders calibration necessary for accurate quantification; however, experimental protocol makes standard postcalibration difficult or in some cases impossible. We have developed a model that utilizes information contained in the background charging current to predict electrode sensitivity to dopamine, ascorbic acid, hydrogen peroxide, and pH shifts at any point in an electrochemical experiment. Analysis determined a high correlation between predicted sensitivity and values obtained using the traditional postcalibration method, across all analytes. To validate this approach in vivo, calibration factors obtained with this model at electrodes in brain tissue were compared to values obtained at these electrodes using a traditional ex vivo calibration. Both demonstrated equal power of predictability for dopamine concentrations. This advance enables in situ electrode calibration, allowing researchers to track changes in electrode sensitivity over time and eliminating the need to generalize calibration factors between electrodes or across multiple days in an experiment. PMID- 24224461 TI - Silk fibroin-based complex particles with bioactive encrustation for bone morphogenetic protein 2 delivery. AB - Application of bone morphogenetic protein 2 (BMP-2) currently faces its challenges, and its efficacy of delivery has to be improved. The proper dosage of the powerful bioactive molecule is still under discussion and needs to be investigated further. In this work, pure silk fibroin particles and particles with calcium carbonate encrustation (complex particles) are designed, developed, and functionalized by BMP-2. These are used to deliver the bioactive molecule to mesenchymal stem cells (MSCs) to induce osteogenic differentiation. Results are compared with those of control groups of BMP-2 carriers under the same condition. Silk fibroin-based particles with size and component variations are prepared by self-assembly, desolvation, and soft template formation to improve BMP-2 loading efficiency. Results show that the particles significantly enhance osteogenic differentiation of MSCs, which is evident in the high ALP enzyme activity as well as the increased level of expression of osteogenic genes. Specifically, the combination of calcium compound and BMP-2 in the silk fibroin-calcium carbonate complex particles synergistically enhances osteogenesis. Release tests and mathematical modeling are applied to describe BMP-2 dissolution profiles, and the release mechanism is based on diffusion and polymer chain relaxation. In summary, the particles show high efficacies of BMP-2 delivery, and introduction of the complex particle can progressively enhance osteogenesis. PMID- 24224462 TI - New oral anticoagulants: an emergency department overview. AB - As of September 2013, three new oral anticoagulants (NOACs) are now available for clinical use on the Pharmaceutical Benefits Scheme in Australia. All three are for stroke prevention in atrial fibrillation, and one will also be available for the treatment of deep venous thrombosis and pulmonary embolism. All have been evaluated in large, multicentre randomised clinical trials. These drugs show at least equivalent efficacy to the current standard of care, the vitamin K antagonist warfarin. Major bleeding rates are overall comparable with warfarin, but there is an important reduction in intracranial bleeding of approximately 50% with all NOAC agents. The NOACs are administered in a simple, fixed dose regimen. There are a few clinically important interactions with other medications or diet. Concerns exist about the potential for irreversible bleeding in the small number of patients in which that occurs. This short report will discuss the pharmacology of these agents, the indications for use, aspects of laboratory monitoring and the management of bleeding with these agents. PMID- 24224463 TI - Switchable magnetism: neutron diffraction studies of the desolvated coordination polymer Co3(OH)2(C4O4)2. AB - We report the magnetic structure of the two magnetically ordered phases of Co3(OH)2(C4O4)2, a coordination polymer that consists of a triangular framework decorated with anisotropic Co(II) ions. Neutron diffraction experiments allow us to confirm that the magnetic behavior changes upon dehydration and reveal the complex phase behavior of this system, relative to the hydrated compound Co3(OH)2(C4O4)2.3H2O. One phase is shown to display spin idle behavior, where only a fraction of the moments order at intermediate temperatures, while at the lowest temperatures the system orders fully, in this case with a net magnetic moment. This novel magnetic behavior is discussed within the framework of a simple Hamiltonian and representational analysis and rationalizes this multiphase behavior by considering the combination of frustration and anisotropy. The change in behavior on dehydration is also rationalized with respect to the changes in the single-ion anisotropy of the cobalt. PMID- 24224464 TI - The chemistry of aromatic osmacycles. AB - Aromatic compounds, such as benzene and its derivatives, porphyrins, fullerenes, carbon nanotubes, and graphene, have numerous applications in biomedicine, materials science, energy science, and environmental science. Metalla-aromatics are analogues of conventional organic aromatic molecules in which one of the (hydro)carbon segments is formally replaced by an isolobal transition-metal fragment. Researchers have studied these transition-metal-containing aromatic molecules for the past three decades, particularly the synthesis and reactivity of metallabenzenes. Another focus has been the preparation and characterization of other metalla-aromatics such as metallafurans, metallapyridines, metallabenzynes, and more. Despite significant advances, remaining challenges in this field include the limited number of convenient and versatile synthetic methods to construct stable and fully characterized metalla-aromatics, and the relative shortage of new topologies. To address these challenges, we have developed new methods for preparing metalla-aromatics, especially those possessing new topologies. Our synthetic efforts have led to a large family of closely related metalla-aromatics known as aromatic osmacycles. This Account summarizes the synthesis and reactivity of these compounds, with a focus on features that are different from those of compounds developed by other groups. These osmacycles can be synthesized from simple precursors under mild conditions. Using these efficient methods, we have synthesized aromatic osmacycles such as osmabenzene, osmabenzyne, isoosmabenzene, osmafuran, and osmanaphthalene. Furthermore, these methods have also created a series of new topologies, such as osmabenzothiazole and osmapyridyne. Our studies of the reactivity of these osma aromatics revealed unprecedented reaction patterns, and we demonstrated the interconversion of several osmacycles. Like other metalla-aromatics, osma aromatics have spectroscopic features of aromaticity, such as ring planarity and the characteristic bond lengths between a single and double bond, but the osma aromatics we have prepared also exhibit good stability towards air, water, and heat. Indeed, some seemingly unstable species proved stable, and their stability made it possible to study their optical, electrochemical, and magnetic properties. The stability of these compouds results from their aromaticity and the phosphonium substituents on the aromatic plane: most of our osma-aromatics carry at least one phosphonium group. The phosphonium group offers stability via both electronic and steric mechanisms. The phosphonium acts as an electron reservoir, allowing the circulation of electron pairs along metallacycles and lowering the electron density of the aromatic rings. Meanwhile, the bulky phosphonium groups surrounding the aromatic metallacycle prevent most reactions that could decompose the skeleton. PMID- 24224466 TI - On the nature of interactions of radicals with polar molecules. AB - Solvated radicals play an important role in many areas of chemistry, but to date, the nature of their interactions with polar solvent molecules lacks chemical interpretation. We present a computational quantum chemical analysis of the binding motives of binary complexes involving electron-poor and electron-rich radicals bound to water and hydrogen fluoride, considered here as model polar solvent molecules. By comparing the binding strengths of several open-shell and closed-shell complexes, in combination with natural localized molecular orbital analysis, we show that open-shell complexes can exhibit additional donor-acceptor interactions relative to analogous closed-shell systems. This may explain the unexpectedly large binding energies observed in some open-shell complexes. These exploratory results show that specific interactions in open-shell systems deserve more attention, and they imply that the quantum mechanical description of explicit solvent molecules needs to be considered carefully when designing simulation protocols for solvated radicals. PMID- 24224465 TI - Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor. AB - The CAR (constitutive androstane receptor; NR1I3) is a critical xenobiotic sensor that regulates xenobiotic metabolism, drug clearance, energy and lipid homoeostasis, cell proliferation and development. Although constitutively active, in hepatocytes CAR is normally held quiescent through a tethering mechanism in the cytosol, anchored to a protein complex that includes several components, including heat-shock protein 90. Release and subsequent nuclear translocation of CAR is triggered through either direct binding to ligand activators such as CITCO {6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4 dichlorobenzyl)oxime} or through indirect chemical activation, such as with PB (phenobarbital). In the present study, we demonstrate that proteasomal inhibition markedly disrupts CAR function, repressing CAR nuclear trafficking, disrupting CAR's interaction with nuclear co-activators and inhibiting induction of CAR target gene responses in human primary hepatocytes following treatment with either PB or CITCO. Paradoxically, these effects occur following accumulation of ubiquitinated hCAR (human CAR). Furthermore, a non-proteolytic function was indicated by its interaction with a SUG1 (suppressor for Gal1), a subunit of the 26S proteasome. Taken together, these data demonstrate that the proteasome complex functions at multiple levels to regulate the functional biology of hCAR activity. PMID- 24224467 TI - Reexpansion pulmonary edema: review of pediatric cases. AB - Reexpansion pulmonary edema (RPE) is an increased permeability pulmonary edema that usually occurs in the reexpanded lung after several days of lung collapse. This condition is recognized to occur more frequently in patients under the age of 40 years, but there has been no detailed analysis of reported pediatric cases of RPE to date. For this review, PubMed literature searches were performed using the following terms: 're(-)expansion pulmonary (o)edema' AND ('child' OR 'children' OR 'infant' OR 'boy' OR 'girl' OR 'adolescent'). The 22 pediatric cases of RPE identified were included in this review. RPE was reported in almost the entire pediatric age range, and as in adult cases, the severity ranged from subclinical to lethal. No specific treatment for RPE was identified, and treatment was administered according to the clinical features of each patient. Of the 22 reported cases, 10 occurred during the perioperative period, but were not related to any specific surgical procedures or anesthetic techniques, or to the duration of lung collapse. Pediatric anesthesiologists should be aware that pediatric RPE can occur after reexpansion of any collapsed lung and that some invasive therapies can be useful in severe cases. PMID- 24224469 TI - Relationships between sperm length and speed differ among three internally and three externally fertilizing species. AB - It is often assumed that longer sperm, by virtue of their increased swimming speed, have a fertilization advantage over shorter sperm when in competition to fertilize eggs. However, there is surprisingly little evidence for a positive correlation between sperm length and speed. Here we use an approach that accounts for within-male variation in sperm traits to examine the relationships between sperm length and sperm speed across a broad range of species, including three internally fertilizing species and three externally fertilizing species. Our results reveal that correlations between sperm size and speed are indeed present and possibly more common than currently thought. However, the direction of the correlations between sperm length and speed, which are more prevalent within a male's ejaculate than among males, were influenced by fertilization mode in contrasting and unexpected ways. Broadly, the patterns revealed that in externally fertilizing species sperm with longer flagellum and shorter heads relative to their flagellum swam faster, whereas in internally fertilizing species sperm with shorter flagellum and longer heads relative to their flagellum swam faster. We discuss these results in light of sperm competition theory and contrast the intraspecific patterns observed in this study with macroevolutionary patterns of sperm evolution reported elsewhere. PMID- 24224468 TI - Oral delivery of double-stranded RNA in larvae of the yellow fever mosquito, Aedes aegypti: implications for pest mosquito control. AB - RNA interference has already proven itself to be a highly versatile molecular biology tool for understanding gene function in a limited number of insect species, but its widespread use in other species will be dependent on the development of easier methods of double-stranded RNA (dsRNA) delivery. This study demonstrates that RNA interference can be induced in the mosquito Aedes aegypti L. (Diptera: Culicidae) simply by soaking larvae in a solution of dsRNA for two hours. The mRNA transcripts for beta-tubulin, chitin synthase-1 and -2, and heat shock protein 83 were reduced between 30 and 50% three days post-dsRNA treatment. The dsRNA was mixed with a visible dye to identify those individuals that fed on the dsRNA, and based on an absence of RNA interference in those individuals that contained no dye within their guts, the primary route of entry of dsRNA is likely through the gut epithelium. RNA interference was systemic in the insects, inducing measurable knock down of gene expression in tissues beyond the gut. Silencing of the beta-tubulin and chitin synthase-1 genes resulted in reduced growth and/or mortality of the larvae, demonstrating the utility of dsRNA as a potential mosquito larvicide. Silencing of chitin synthase-2 did not induce mortality in the larvae, and silencing of heat shock protein 83 only induced mortality in the insects if they were subsequently subjected to a heat stress. Drosophila melanogaster Meigen (Diptera: Drosophilidae) larvae were also soaked in dsRNA designed to specifically target either their own beta-tubulin gene, or that of A. aegypti, and significant mortality was only seen in larvae treated with dsRNA targeting their own gene, which suggests that dsRNA pesticides could be designed to be species-limited. PMID- 24224470 TI - Ag2S quantum dots conjugated chitosan nanospheres toward light-triggered nitric oxide release and near-infrared fluorescence imaging. AB - Nanoscaled light-triggered nitric oxide (NO) delivery vehicles with the ability of near-infrared (NIR) fluorescence imaging was presented, which consisted of chitosan (CS)-based S-nitrosothiols (SNO) and encapsulated silver sulfide quantum dots (Ag2S QDs). CS-SNO compounds that bore NO-storing functional groups were prepared via amino modification of chitosan. Water-soluble Ag2S QDs were synthesized and conjugated with the CS-SNO compounds with the aid of ethylenediaminetetraacetic acid (EDTA). The biocompatible Ag2S-CS-SNO nanospheres, with dimension of ~117 nm, exhibited bright NIR fluorescence and satisfactory photostability under NIR irradiation. The Ag2S-CS-SNO nanospheres could release NO under irradiation of UV or visible light at physiological pH and temperature yet would hardly release NO if NIR irradiation was applied. Cell imaging was successfully performed, demonstrating that the Ag2S-CS-SNO nanospheres could emit readily observable NIR fluorescence and release NO in living cells. The NIR fluorescence imaging of the Ag2S-CS-SNO nanospheres did not interfere with the light-triggered NO release from them, which would provide new perspectives for the application of multifunctional nanostructured materials in diagnostics and imaging. PMID- 24224472 TI - Neuroprotective and symptomatic effects of targeting group III mGlu receptors in neurodegenerative disease. AB - Neurodegenerative disorders possess common pathological mechanisms, such as protein aggregation, inflammation, oxidative stress (OS) and excitotoxicity, raising the possibility of shared therapeutic targets. As a result of the selective cellular and regional expression of group III metabotropic glutamate (mGlu) receptors, drugs targeting such receptors have demonstrated both neuroprotective properties and symptomatic improvements in several models of neurodegeneration. In recent years, the discovery and development of subtype selective ligands for the group III mGlu receptors has gained pace, allowing further research into the functions of these receptors and revealing their roles in health and disease. Activation of this class of receptors results in neuroprotection, with a variety of underlying mechanisms implicated. Group III mGlu receptor stimulation prevents excitotoxicity by inhibiting glutamate release from neurons and microglia and increasing glutamate uptake by astrocytes. It also attenuates the neuroinflammatory response by reducing glial reactivity and encourages neurotrophic phenotypes. This article will review the current literature with regard to the neuroprotective and symptomatic effects of group III mGlu receptor activation and discuss their promise as therapeutic targets in neurodegenerative disease. We review the neuroprotective and symptomatic effects of targeting group III mGlu receptors in neurodegenerative disease: Excess extracellular glutamate causes overactivation of NMDA receptors resulting in excitotoxicity. Externalization of phosphatidylserine stimulates phagocytosis of neurons by activated microglia, which contribute to damage through glutamate and pro-inflammatory factor release. Reactive astrocytes produce cytotoxic factors enhancing neuronal cell death. Activation of group III mGlu receptors by glutamate and/or mGlu receptor ligands results in inhibition of glutamate release from presynaptic terminals and microglia, reducing excitotoxicity. Astrocytic glutamate uptake is increased and microglia produce neurotrophic factors. PMID- 24224471 TI - OX40L blockade and allergen-induced airway responses in subjects with mild asthma. AB - BACKGROUND: The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells. OBJECTIVE: We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma. METHODS: Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-group trial (ClinicalTrials.gov identifier NCT00983658) to compare blockade of OX40L using a humanized anti-OX40L MAb to placebo-administered intravenously in 4 doses over 3 months. Allergen inhalation challenges were carried out 56 and 113 days after the first dose of study drug. The primary outcome variable was the late-phase asthmatic response. Other outcomes included the early-phase asthmatic response, airway hyperresponsiveness, serum IgE levels, blood and sputum eosinophils, safety and tolerability. RESULTS: Treatment with anti-OX40L MAb did not attenuate the early- or late-phase asthmatic responses at days 56 or 113 compared with placebo. In the anti-OX40L MAb treatment group, total IgE was reduced 17% from pre-dosing levels, and sputum eosinophils decreased 75% by day 113 (both P = 0.04). There was no effect of anti-OX40L MAb on airway hyperresponsiveness or blood eosinophils. The frequency of AEs was similar in both groups. CONCLUSION AND CLINICAL RELEVANCE: Pharmacological activity of anti-OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post-dosing, but there was no effect on allergen induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses. PMID- 24224473 TI - Determination of extremely high pressure tolerance of brine shrimp larvae by using a new pressure chamber system. AB - Hydrostatic pressure is the only one of a range of environmental parameters (water temperature, salinity, light availability, and so on) that increases in proportion with depth. Pressure tolerance is therefore essential to understand the foundation of populations and current diversity of faunal compositions at various depths. In the present study, we used a newly developed pressure chamber system to examine changes in larval activity of the salt-lake crustacean, Artemia franciscana, in response to a range of hydrostatic pressures. We showed that A. franciscana larvae were able to survive for a short period at pressures of <= 60 MPa (approximately equal to the pressure of 6000 m deep). At a pressure of > 20 MPa, larval motor ability was suppressed, but not lost. Meanwhile, at a pressure of > 40 MPa, some of the larval motor ability was lost without recovery after decompression. For all experiments, discordance of movement and timing between right and left appendages, was observed at pressures of > 20 MPa. Our results indicate that the limit of pressure for sustaining active behavior of A. franciscana larvae is ~20 MPa, whereas the limit of pressure for survival is within the range 30-60 MPa. Thus, members of the genus Artemia possess the ability to resist a higher range of pressures than their natural habitat depth. Our findings demonstrated an example of an organism capable of invading deeper environment in terms of physical pressure tolerance, and indicate the need and importance of pressure study as an experimental method. PMID- 24224474 TI - Carbon nanotube scaffolds instruct human dendritic cells: modulating immune responses by contacts at the nanoscale. AB - Nanomaterials interact with cells and modify their function and biology. Manufacturing this ability can provide tissue-engineering scaffolds with nanostructures able to influence tissue growth and performance. Carbon nanotube compatibility with biomolecules motivated ongoing interest in the development of biosensors and devices including such materials. More recently, carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or to instruct the growth and organization of neural networks. To gather further knowledge on the true potential of future constructs, in particular to assess their immune-modulatory action, we evaluate carbon nanotubes interactions with human dendritic cells (DCs). DCs are professional antigen-presenting cells and their behavior can predict immune responses triggered by adhesion-dependent signaling. Here, we incorporate DC cultures to carbon nanotubes and we show by phenotype, microscopy, and transcriptional analysis that in vitro differentiated and activated DCs show when interfaced to carbon nanotubes a lower immunogenic profile. PMID- 24224475 TI - Phantom limb pain: a systematic neuroanatomical-based review of pharmacologic treatment. AB - OBJECTIVE: Review the current evidence-based pharmacotherapy for phantom limb pain (PLP) in the context of the current understanding of the pathophysiology of this condition. DESIGN: We conducted a systematic review of original research papers specifically investigating the pharmacologic treatment of PLP. Literature was sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies with animals, "neuropathic" but not "phantom limb" pain, or without pain scores and/or functional measures as primary outcomes were excluded. A level of evidence 1-4 was ascribed to individual treatments. These levels included meta-analysis or systematic reviews (level 1), one or more well-powered randomized, controlled trials (level 2), retrospective studies, open label trials, pilot studies (level 3), and anecdotes, case reports, or clinical experience (level 4). RESULTS: We found level 2 evidence for gabapentin, both oral (PO) and intravenous (IV) morphine, tramadol, intramuscular (IM) botulinum toxin, IV and epidural Ketamine, level 3 evidence for amitriptyline, dextromethorphan, topiramate, IV calcitonin, PO memantine, continuous perineural catheter analgesia with ropivacaine, and level 4 evidence for methadone, intrathecal (IT) buprenorphine, IT and epidural fentanyl, duloxetine, fluoxetine, mirtazapine, clonazepam, milnacipran, capsaicin, and pregabalin. CONCLUSIONS: Currently, the best evidence (level 2) exists for the use of IV ketamine and IV morphine for the short-term perioperative treatment of PLP and PO morphine for an intermediate to long-term treatment effect (8 weeks to 1 year). Level 2 evidence is mixed for the efficacy of perioperative epidural anesthesia with morphine and bupivacaine for short to long-term pain relief (perioperatively up to 1 year) as well as for the use of gabapentin for pain relief of intermediate duration (6 weeks). PMID- 24224476 TI - Risk factors associated with self-reported symptoms of digital ischemia in elite male volleyball players in the Netherlands. AB - One in every four elite male volleyball players in the Netherlands reported blue or pale digits in the dominant hand. Little is known about risk factors. To assess whether personal-, sports-, and work-related risk factors are associated with these symptoms in these volleyball players, a survey was performed among elite male volleyball players in the Dutch national top league and in the Dutch beach volleyball team. The questionnaire assessed the presence of symptoms and risk factors. Binary logistic regression was performed to calculate odds ratios (ORs). A total of 99 of the 107 athletes participated - a response rate of 93%. Two sports-related risk factors were associated with symptoms of blue or pale digits: 18-30 years playing volleyball [OR = 6.70; 95% confidence interval (CI) 1.12-29.54] and often/always performing weight training to increase dominant limb strength (OR = 2.70; 95% CI 1.05-6.92). No significant other sports-, personal-, or work-related risk factors were found. Playing volleyball for more than 17 years and often/always performing weight training to increase dominant limb strength were independently associated with an increased risk on ischemia-related complaints of the dominant hand in elite male volleyball players. PMID- 24224477 TI - Effect of the infectious dose and the presence of hepatitis C virus core gene on mouse intrahepatic CD8 T cells. AB - AIM: Chronic hepatitis C viral (HCV) infections often result in ineffective CD8 T cell responses due to functional exhaustion of HCV-specific T cells. However, how persisting HCV impacts CD8 T-cell effector functions remains largely unknown. The aim of this study is to examine the effect of the infectious dose and the presence of HCV core gene. METHODS: We compared responses of intrahepatic CD8 T cells during infection of wild-type or HCV core transgenic (Tg) mice with various infectious doses of HCV-NS3-expressing recombinant adenovirus (Ad-HCV-NS3). RESULTS: Using major histocompatibility complex class I tetramer and intracellular interferon (IFN)-gamma staining method to track HCV-NS3-specific CD8 T cells, we found that a significant expansion of HCV-NS3-specific CD8 T cells was restricted to a very narrow dosage range. IFN-gamma production by intrahepatic CD8 T cells in HCV core Tg mice was suppressed as compared with wild type mice. Higher levels of expression of regulatory molecules, Tim-3 and PD-1, by intrahepatic CD8 T cells and PD-L1 by intrahepatic antigen-presenting cells were observed in HCV core Tg mice following Ad-HCV-NS3 infection, and the expression increased dependent on infectious dose. Furthermore, we found a significant inverse correlation between the percentages of IFN-gamma-producing cells and expression of regulatory molecules in antigen-specific intrahepatic CD8 T cells. CONCLUSION: High infectious dose and the presence of HCV core gene were strongly involved in ineffective CD8 T-cell responses. We consider that HCV core Tg mouse infected with high infectious dose of Ad-HCV-NS3 is useful as a chronic infection model in the development of immunotherapy for chronic hepatitis C. PMID- 24224478 TI - Study of stem cell marker nestin and its correlation with vascular endothelial growth factor and microvascular density in ependymomas. AB - BACKGROUND: Ependymomas are relatively rare glial tumours, whose pathogenesis is not well elucidated. They are enigmatic tumours that show site-specific differences in their biological behaviour. Recent studies have hypothesized that ependymoma cancer stem cells (CSCs) are derived from radial glia and express stem cell markers such as nestin, which is associated with a poor prognosis. CSCs reside in 'vascular niches', where endothelial cells and molecular signals like vascular endothelial growth factor (VEGF) play an important role in their survival. Studies analysing VEGF expression in ependymomas showed that ependymal vascular proliferation is less sensitive to induction by VEGF, questioning the possible beneficial effect of anti-VEGF therapy in ependymomas. We aimed to study nestin and VEGF immunoexpression in ependymomas, correlate them with clinicopathological parameters and reveal a role for VEGF in ependymomas that extends beyond the context of tumour angiogenesis. METHODS: We analysed 126 cases of ependymomas of different grades and locations for nestin and VEGF immunoexpression. Endothelial cells were labelled with CD34. Vascular patterns and microvascular density was determined. RESULTS: Nestin and VEGF expression in tumour cells were more frequent in supratentorial tumours [89% (33/37) and 65% (24/37) respectively], and were associated with a significantly poor progression free survival (PFS). VEGF expression did not reveal any correlation with necrosis or bizarre vascular patterns. CONCLUSIONS: Supratentorial location is an independent predictor of a poor PFS. Significant coexpression of nestin and VEGF suggests that latter possibly augments stem cell survival. Thus, anti-VEGF therapy may be a good option in future for nestin immunopositive ependymomas. PMID- 24224479 TI - Analysis of the thyroid phenotype in 42 patients with Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct. AB - BACKGROUND: Pendred syndrome (PS), a recessive disorder caused by mutations in the SLC26A4 (PDS) gene, is associated with deafness and goiter. SLC26A4 mutations have also been identified in patients exhibiting isolated sensorineural hearing loss without apparent thyroid abnormality (nonsyndromic enlargement of the vestibular aqueduct; nonsyndromic EVA). Our aim was to describe systematically the thyroidal phenotypes and the SLC26A4 genotypes of patients presenting with PS or nonsyndromic EVA. METHODS: Nineteen patients with PS and 23 patients with nonsyndromic EVA, aged 5-53 years, were included. They underwent thyroid evaluation (physical examination, biological thyroid function tests, measurement of thyroglobulin level, thyroid ultrasonography, and thyroid (123)I scintigraphy with perchlorate discharge test), otological evaluation, and SLC26A4 mutation screening. RESULTS: In 19 patients with PS, goiter was identified in 15 (79%) and hypothyroidism in 15 (79%); hypothyroidism was subclinical in four patients and congenital in six patients. The perchlorate discharge test (PDT) was positive in 10/16 (63%). Morphological evaluation of the inner ear using MRI and/or CT showed bilateral EVA in 15/15 PS patients. Mutation screening revealed two SLC26A4 mutant alleles in all 19 PS patients that were homozygous in two families and compound heterozygous in 12 families. In the 23 patients with nonsyndromic EVA, systematic thyroid evaluation found no abnormalities except for slightly increased thyroglobulin levels in two patients. SLC26A4 mutations were identified in 9/23 (39%). Mutations were biallelic in two (compound heterozygous) and monoallelic in seven patients. CONCLUSION: The thyroid phenotype is widely variable in PS. SLC26A4 mutation screening is needed in patients exhibiting PS or nonsyndromic EVA. PS is associated with biallelic SLC26A4 mutations and nonsyndromic EVA with no, monoallelic, or biallelic SLC26A4 mutations. Systematic thyroid evaluation is recommended in patients with nonsyndromic EVA associated with one or two SLC26A4 mutations. We propose using a combination of three parameters to define and diagnose PS: (i) sensorineural deafness with bilateral EVA; (ii) thyroid abnormality comprising goiter and/or hypothyroidism and/or a positive PDT; (iii) biallelic SLC26A4 mutations. PMID- 24224480 TI - Totally intracorporeal robot-assisted radical cystectomy: optimizing total outcomes. AB - We performed a systematic literature review to assess the current status of a totally intracorporeal robot-assisted radical cystectomy (RARC) approach. The current 'gold standard' for radical cystectomy remains open radical cystectomy. RARC has lagged behind robot-assisted prostatectomy in terms of adoption and perceived patient benefit, but there are indications that this is now changing. There have been several recently published large series of RARC, both with extracorporeal and with intracorporeal urinary diversions. The present review focuses on the totally intracorporeal approach. Radical cystectomy is complex surgery with several important outcome measures, including oncological and functional outcomes, complication rates, patient recovery and cost implications. We aim to answer the question of whether there are advantages to a totally intracorporeal robotic approach or whether we are simply making an already complex procedure more challenging with an associated increase in complication rates. We review the current status of both oncological and functional outcomes of totally intracorporeal RARC compared with standard RARC with extraperitoneal urinary diversion and with open radical cystectomy, and assess the associated short- and long-term complication rates. We also review aspects in training and research that have affected the uptake of RARC. Additionally we evaluate how current technology is contributing to the future development of this surgical technique. PMID- 24224481 TI - Learning to spell from reading: general knowledge about spelling patterns influences memory for specific words. AB - Adults often learn to spell words during the course of reading for meaning, without intending to do so. We used an incidental learning task in order to study this process. Spellings that contained double n, r and t which are common doublets in French, were learned more readily by French university students than spellings that contained less common but still legal doublets. When recalling or recognizing the latter, the students sometimes made transposition errors, doubling a consonant that often doubles in French rather than the consonant that was originally doubled (e.g., tiddunar recalled as tidunnar). The results, found in three experiments using different nonwords and different types of instructions, show that people use general knowledge about the graphotactic patterns of their writing system together with word-specific knowledge to reconstruct spellings that they learn from reading. These processes contribute to failures and successes in memory for spellings, as in other domains. PMID- 24224482 TI - Diaper dermatitis: etiology, manifestations, prevention, and management. AB - Pediatricians and parents report diaper dermatitis (DD) to be one of the most common skin diseases that affects almost every child at some point during the early months and years of life. Diapered skin is exposed to friction and excessive hydration, has a higher pH than nondiapered skin, and is repeatedly soiled with feces that contains enzymes with high irritation potential for the skin. The combination of these factors frequently results in skin damage, leading to visible erythematous lesions that can be irritating and painful to the child. Behavioral changes such as increased crying and agitation and changes in eating and sleeping patterns indicate emotional distress. Appropriate skin care can help to prevent the occurrence of DD and to speed up the healing of affected skin. This includes frequent diaper changes and aeration, gentle cleansing, and the use of a barrier cream. Mild to moderate cases usually resolve after a few days of following this routine, but the use of harsh cleaning products can exacerbate DD. PMID- 24224483 TI - Advanced kidney cancer: treating the elderly. AB - Advancing age represents the primary risk factor for renal tumors. Despite findings on the inhibition of angiogenesis that have led to six new drugs to treat metastatic renal cell carcinoma, elderly patients have not been fully represented in clinical trials. In addition, current opinions regarding nephrectomy in elderly patients are conflicting. Available data refer to the efficacy and safety of sorafenib, sunitinib, everolimus, bevacizumab and temsirolimus in patients aged 65 years and older; safety and efficacy data are available only for sunitinib, sorafenib,and everolimus in patients aged 70 years and older and only sorafenib has safety data for patients aged 75 years and older. A different approach based on evaluating comorbidities at baseline, risk of drug interactions and the impact of antitumor treatment in patients with polytherapy regimen is discussed. A decision-making algorithm is proposed to facilitate the selection of the best therapy for kidney tumors for a specific elderly patient profile. PMID- 24224484 TI - Natural history of postvascular-phase iso-enhanced lesions on the sonogram in chronic liver diseases. AB - BACKGROUND AND AIM: This study examined the natural history of postvascular-phase iso-enhanced lesions (PIELs) on contrast-enhanced sonograms to determine the potential risk and predictive factors for developing hepatocellular carcinoma (HCC) in chronic liver diseases. METHODS: This prospective study included 87 PIELs on contrast-enhanced sonograms (postvascular-phase: 10 min post-injection of perflubutane microbubbles) in 72 patients with chronic liver diseases (45 males and 27 females; age 65.0 +/- 10.8y; PIEL diameter 12.5 +/- 4.2 mm). The PIELs were followed up by ultrasound/contrast-enhanced ultrasound, computed tomography, or magnetic resonance imaging at 3 to 6 months intervals. RESULTS: Twenty patients developed HCCs during the study period (median, 22.0 months). The cumulative risk of HCC occurrence was 7.9% at 1 year and 36.0% at 3 years. The presence of coexistent HCC (hazard ratio [HR], 4.975; 95% confidence interval [CI], 1.729-14.316; P = 0.003) and alpha-fetoprotein > 20 ng/mL (HR, 4.104; 95% CI, 1.621-10.392; P = 0.003) were significant factors for the risk of HCC occurrence. Fourteen of these lesions were diagnosed as HCCs that developed from iso-enhanced lesions. Cumulative HCC occurrence rates from PIEL > 14 mm was 23.5% at 1 year and 46.3% at 3 years. Cox regression analysis showed that PIEL > 14 mm (HR, 6.780; 95% CI, 2.060-22.32; P = 0.002) and alpha-fetoprotein > 20 ng/mL (HR, 4.892; 95% CI, 1.559-15.350; P = 0.007) were statistically significant factors for HCC occurrence. CONCLUSIONS: Patients with coexistent HCC, alpha-fetoprotein > 20 ng/mL, or PIEL > 14 mm should be carefully monitored because of the high potential for HCC occurrence. PMID- 24224485 TI - SIM-dependent enhancement of substrate-specific SUMOylation by a ubiquitin ligase in vitro. AB - SIMs (SUMO-interaction motifs), which mediate the non-covalent binding of SUMO (small ubiquitin-related modifier) to other proteins, are usually involved in the recognition of SUMOylated substrates by downstream effectors that transmit the biological signal of the modification. In ubiquitin ligase Rad18 (radiation sensitive 18) from Saccharomyces cerevisiae, a SIM, contributes to the recognition of SUMOylated PCNA (proliferating-cell nuclear antigen) as its physiological ubiquitylation target. In the present study we show that Rad18 is also capable of enhancing PCNA SUMOylation in a SIM-dependent manner in vitro, most probably by means of directing SUMO-loaded Ubc9 (ubiquitin-conjugating enzyme 9) towards the substrate. The process shares important features with Rad18 dependent ubiquitylation, such as an exquisite specificity for the modification site on PCNA and the requirement of DNA, and the reaction proceeds under conditions that are widely used in other in vitro assays for SUMO ligase activity. However, there is no evidence that Rad18 contributes to PCNA SUMOylation in vivo. The findings of the present study therefore illustrate the problematic nature of in vitro SUMOylation assays and highlight the danger of extrapolating from this type of experiment to the biological function of a SUMO interacting protein. PMID- 24224487 TI - High-temperature, high-pressure hydrothermal synthesis, crystal structures, and spectroscopic studies of a uranium(IV) phosphate (Na10U2P6O24) and the isotypic cerium(IV) phosphate (Na10Ce2P6O24). AB - A uranium(IV) phosphate, Na10U2P6O24, was synthesized under hydrothermal conditions at 570 degrees C and 160 MPa and structurally characterized by single crystal X-ray diffraction. The valence state of uranium was established by UV-vis and U 4f X-ray photoelectron spectroscopy. The powder sample has a second harmonic-generation signal, confirming the absence of a center of symmetry in the structure. The structure contains UO8 snub-disphenoidal polyhedra that are linked to monophosphate tetrahedra by vertex and edge sharing such that a three dimensional framework with intersecting 12-sided circular and rectangular channels is formed. All 10 sodium sites are situated inside the channels and are fully occupied. This is the first uranium(IV) phosphate synthesized under high temperature, high-pressure hydrothermal conditions. The isotypic cerium(IV) phosphate, Na10Ce2P6O24, was also synthesized under the same hydrothermal conditions. It is the first structurally characterized Ce(IV) phosphate with a P/Ce ratio of 3. Crystal data of Na10U2P6O24: orthorhombic, P212121 (No. 19), a = 6.9289(3) A, b = 16.1850(7) A, c = 18.7285(7) A, V = 2100.3(2) A(3), Z = 4, R1 = 0.0304, and wR2 = 0.0522. Crystal data of Na10Ce2P6O24: orthorhombic, P2(1)2(1)2(1) (No. 19), a = 6.9375(14) A, b = 16.215(3) A, c = 18.765(4) A, V = 2111.0(7) A(3), Z = 4, R1 = 0.0202, and wR2 = 0.0529. PMID- 24224486 TI - Purinergic stimulation of K+-dependent Na+/Ca2+ exchanger isoform 4 requires dual activation by PKC and CaMKII. AB - K+-dependent Na+/Ca2+-exchanger isoform 4 (NCXK4) is one of the most broadly expressed members of the NCKX (K+-dependent Na+/Ca2+-exchanger) family. Recent data indicate that NCKX4 plays a critical role in controlling normal Ca2+ signal dynamics in olfactory and other neurons. Synaptic Ca2+ dynamics are modulated by purinergic regulation, mediated by ATP released from synaptic vesicles or from neighbouring glial cells. Previous studies have focused on modulation of Ca2+ entry pathways that initiate signalling. Here we have investigated purinergic regulation of NCKX4, a powerful extrusion pathway that assists in terminating Ca2+ signals. NCKX4 activity was stimulated by ATP through activation of the P2Y receptor signalling pathway. Stimulation required dual activation of PKC (protein kinase C) and CaMKII (Ca2+/calmodulin-dependent protein kinase II). Mutating T312, a putative PKC phosphorylation site on NCKX4, partially prevented purinergic stimulation. These data illustrate how purinergic regulation can shape the dynamics of Ca2+ signalling by activating a signal damping and termination pathway. PMID- 24224488 TI - Methemoglobin generation by 8-aminoquinolines: effect of substitution at 5 position of primaquine. AB - Currently, the only clinically approved antimalarial drug to treat relapsing malaria is primaquine (PQ), yet PQ administration can cause life-threatening hemolytic anemia in some patients. In our efforts to understand the connection between PQ and methemoglobin formation, the effect of 5-substituted primaquine derivatives on the basicity of hemoglobin-bound O2 was investigated using various computational methods, including quantum mechanics/molecular mechanics (QM/MM) calculations, molecular dynamics simulations and density functional theory calculations, to determine the geometries, relative energies, spin densities, proton affinities and ionization potentials of various PQ derivatives and PQ...hemoglobin complexes. We found that the protein environment and solvent do not change our previously proposed methemoglobin formation mechanism that 5 hydroxyprimaquine donates an electron to O2, facilitating its conversion to H2O2 and generating methemoglobin. Because of 5-hydroxyprimaquine's ability to lose an electron by this mechanism, we then used different substituents at primaquine's 5 position and found that an electron-withdrawing group (EWG) increases the ionization potential of the corresponding derivative. As a result, the EWG substituted derivatives make the hemoglobin-bound O2 less basic, because of their weaker electron-donating ability. These derivatives hence are predicted to have a lower propensity to generate methemoglobin, which can inform future design of less hemotoxic antimalarial drugs. We also carried out experimental measurement of methemoglobin formation for some of the 5-substituted derivatives. PMID- 24224490 TI - Pigmented chin papillomas in red (Cervus elaphus) x wapiti (Cervus canadensis) stags associated with a novel papillomavirus. AB - CASE HISTORY: Lesions were observed on the chins of two 2- to 3-year-old red (Cervus elaphus) x wapiti (Cervus canadensis) stags from the lower North Island of New Zealand during velvet removal. CLINICAL FINDINGS: Both stags had numerous, coalescing, darkly pigmented plaques and nodules on the skin of the chin and lower lips that were 3-10 mm in diameter. Re-examination after 12 months of initial detection revealed no appreciable change in the lesions. A biopsy sample from one lesion was submitted for histopathological examination. HISTOPATHOLOGY: Sections revealed lesions consistent with pigmented viral papillomas, characterised by marked epidermal hyperplasia forming papillary fronds, prominent clumping of keratohyalin granules, keratinocytes with dilated grey-blue cytoplasm, shrunken nuclei surrounded by a clear halo (koilocytes), and presumptive viral intranuclear inclusions. Papillomavirus DNA was amplified by PCR from a fresh tissue sample from the same papilloma. Comparison of the partial nucleotide sequence amplified to previously reported papillomaviruses suggested the presence of a novel papillomavirus type. DIAGNOSIS: A presumptive diagnosis of pigmented viral papilloma was made. CLINICAL RELEVANCE: While the papillomas described in these two cases do not appear to cause major clinical disease, they are visually unappealing and have the potential to spread to other valuable deer. PMID- 24224491 TI - Renewal of the air-water interface as a critical system parameter of protein stability: aggregation of the human growth hormone and its prevention by surface active compounds. AB - Soluble proteins are often highly unstable under mixing conditions that involve dynamic contacting between the main liquid phase and a gas phase. The recombinant human growth hormone (rhGH) was recently shown to undergo aggregation into micrometer-sized solid particles composed of non-native (mis- or unfolded) protein, once its solutions were stirred or shaken to generate a continuously renewed air-water interface. To gain deepened understanding and improved quantification of the air-water interface effect on rhGH stability, we analyzed the protein's aggregation rate (r(agg)) at controlled specific air-water surface areas (a(G/L)) established by stirring or bubble aeration. We show that in spite of comparable time-averaged values for a(G/L) (~ 100 m(2)/m(3)), aeration gave a 40-fold higher r(agg) than stirring. The enhanced r(agg) under aeration was ascribed to faster macroscopic regeneration of free a(G/L) during aeration as compared to stirring. We also show that r(agg) was independent of the rhGH concentration in the range 0.67 - 6.7 mg/mL, and that it increased linearly dependent on the available a(G/L). The nonionic surfactant Pluronic F-68, added in 1.6-fold molar excess over rhGH present, resulted in complete suppression of r(agg). Foam formation was not a factor influencing r(agg). Using analysis by circular dichroism spectroscopy and small-angle X-ray scattering, we show that in the presence of Pluronic F-68 under both stirring and aeration, the soluble protein retained its original fold, featuring native-like relative composition of secondary structural elements. We further provide evidence that the efficacy of Pluronic F-68 resulted from direct, probably hydrophobic protein-surfactant interactions that prevented rhGH from becoming attached to the air-water interface. Surface-induced aggregation of rhGH is suggested to involve desorption of non-native protein from the air-water interface as the key limiting step. Proteins or protein aggregates released back into the bulk liquid appear to be essentially insoluble. PMID- 24224492 TI - Glycosaminoglycans, hyperglycemia, and disease. AB - SIGNIFICANCE: Diabetes is a widespread disease with many clinical pathologies. Despite numerous pharmaceutical strategies for treatment, the incidence of diabetes continues to increase. Hyperglycemia, observed in diabetes, causes endothelial injury resulting in microvascular and macrovascular complications such as nephropathy, retinopathy, neuropathy, and increased atherosclerosis. RECENT ADVANCES: Proteoglycans are chemically diverse macromolecules consisting of a protein core with glycosaminoglycans (GAGs) attached. Heparan sulfate proteoglycans are important compounds found on the endothelial cell membrane and in the extracellular matrix, which play an important role in growth regulation and serve as a reservoir for cytokines and other bioactive molecules. Endothelial cells are altered in hyperglycemia by a reduction in heparan sulfate and upregulation and secretion of heparanase, an enzyme that degrades heparan sulfate GAGs on proteoglycans. Reactive oxygen species, increased in diabetes, also destroy GAGs. CRITICAL ISSUES: Preservation of heparan sulfate proteoglycans on endothelial cells may be a strategy to prevent angiopathy associated with diabetes. The use of GAGs and GAG-like compounds may increase endothelial heparan sulfate and prevent an increase in the heparanase enzyme. FUTURE DIRECTIONS: Elucidating the mechanisms of GAG depletion and its significance in endothelial health may help to further understand, prevent, and treat cardiovascular complications associated with diabetes. Further studies examining the role of GAGs and GAG-like compounds in maintaining endothelial health, including their effect on heparanase, will determine the feasibility of these compounds in diabetes treatment. Preservation of heparan sulfate by decreasing heparanase may have important implications not only in diabetes, but also in cardiovascular disease and tumor biology. PMID- 24224493 TI - Organocatalytic enantioselective synthesis of 2,3-allenoates by intermolecular addition of nitroalkanes to activated enynes. AB - The first efficient intermolecular addition of nitroalkanes to activated enynes for asymmetric synthesis of 2,3-allenoates is described. It is a new addition to the limited available strategies for catalytic asymmetric synthesis of allenoates. Enabled by a new bifunctional catalyst, a range of trisubstituted allenoates can be obtained in excellent chemical and optical purity. These allenoate products with a pendant 2-nitroethyl alpha-substituent are useful chiral building blocks. PMID- 24224494 TI - Cell culturability of Pseudomonas protegens CHA0 depends on soil pH. AB - Pseudomonas inoculants may lose colony-forming ability in soil, but soil properties involved are poorly documented. Here, we tested the hypothesis that soil acidity could reduce persistence and cell culturability of Pseudomonas protegens CHA0. At 1 week in vitro, strain CHA0 was found as culturable cells at pH 7, whereas most cells at pH 4 and all cells at pH 3 were noncultured. In 21 natural soils of contrasted pH, cell culturability loss of P. protegens CHA0 took place in all six very acidic soils (pH < 5.0) and in three of five acidic soils (5.0 < pH < 6.5), whereas it was negligible in the neutral and alkaline soils at 2 weeks and 2 months. No correlation was found between total cell counts of P. protegens CHA0 and soil composition data, whereas colony counts of the strain correlated with soil pH. Maintenance of cell culturability in soils coincided with a reduction in inoculant cell size. Some of the noncultured CHA0 cells were nutrient responsive in Kogure's viability test, both in vitro and in soil. Thus, this shows for the first time that the sole intrinsic soil composition factor triggering cell culturability loss in P. protegens CHA0 is soil acidity. PMID- 24224495 TI - Demonstration of an electrochemical liquid cell for operando transmission electron microscopy observation of the lithiation/delithiation behavior of Si nanowire battery anodes. AB - Over the past few years, in situ transmission electron microscopy (TEM) studies of lithium ion batteries using an open-cell configuration have helped us to gain fundamental insights into the structural and chemical evolution of the electrode materials in real time. In the standard open-cell configuration, the electrolyte is either solid lithium oxide or an ionic liquid, which is point-contacted with the electrode. This cell design is inherently different from a real battery, where liquid electrolyte forms conformal contact with electrode materials. The knowledge learnt from open cells can deviate significantly from the real battery, calling for operando TEM technique with conformal liquid electrolyte contact. In this paper, we developed an operando TEM electrochemical liquid cell to meet this need, providing the configuration of a real battery and in a relevant liquid electrolyte. To demonstrate this novel technique, we studied the lithiation/delithiation behavior of single Si nanowires. Some of lithiation/delithation behaviors of Si obtained using the liquid cell are consistent with the results from the open-cell studies. However, we also discovered new insights different from the open cell configuration-the dynamics of the electrolyte and, potentially, a future quantitative characterization of the solid electrolyte interphase layer formation and structural and chemical evolution. PMID- 24224496 TI - Prevalence and molecular characterization of AmpC-producing clinical isolates of Escherichia coli from southeastern Iran. AB - BACKGROUND AND OBJECTIVE: AmpC in Escherichia coli is noninducible but is regulated by promoter and attenuator mechanisms and can be expressed at high levels as a result of a mutation. This study was undertaken to characterize the AmpC hyperproducing clinical isolates of E. coli. METHODS: E. coli isolates recovered from three major hospitals in Zahedan, South Eastern Iran, were selected on the basis of resistance phenotype to the third-generation cephalosporins and cefoxitin. Phenyl boronic acid as an inhibitor and cefoxitin were used to confirm the overexpression of AmpC. The presence of genes encoding ACC, FOX, MOX, DHA, CIT, and EBC was detected using multiplex PCR. The existence of mutations in the regulatory region of the chromosomal ampC gene was assessed using PCR and sequencing. RESULTS: Thirteen of 392 E. coli isolates were selected as high-level AmpC producers. Eleven of the 13 isolates contained the blaCMY-2 gene; 12 of the 13 AmpC hyperproducing strains harbored changes in the promoter/attenuator region, which could explain the increased expression of the chromosome-encoded AmpC enzyme. In 10 of the 13 strains, we found both chromosomal- and plasmid-mediated mechanisms responsible for AmpC production. INTERPRETATION AND CONCLUSIONS: AmpC hyperproducing E. coli isolates exhibit significant resistance to cephalosporins. This work showed that strains hyperproducing chromosomal AmpC could be as frequent as strains with plasmid mediated AmpC hyperproduction. PMID- 24224497 TI - Prevalence and molecular characterization of fluoroquinolone resistance in Escherichia coli isolates from dairy cattle with endometritis in China. AB - Fluoroquinolones are frequently used to treat infectious disease that is caused by Escherichia coli in dairy cattle. However, fluoroquinolone resistance occurs and is due either to chromosomal mutations in the bacterial topoisomerase genes and/or to plasmid-mediated resistance genes. The purpose of this study was to determine the prevalence and molecular characteristics of fluoroquinolone resistance determinants in E. coli strains (n=148) isolated from dairy cattle with bovine endometritis in Inner Mongolia (China). Analysis of the mutations in the quinolone resistance-determining regions of resistant E. coli isolates confirmed previously reported substitutions in the GyrA and ParE. However, we identified additional substitutions in the ParC and GyrB that have not been reported earlier. No plasmid-mediated quinolone resistance genes in any of the isolates were found. The number of point mutations found per isolate correlated with an increase in the minimum inhibitory concentration of ciprofloxacin. Overall, 45.5% of the isolates were positive for the class I integrase gene along with four gene cassettes that were responsible for resistance to trimethoprim (dfr1 and dfrA17) and aminoglycosides (aadA1 and aadA5), respectively. The prevalence of extended-spectrum beta-lactamases (ESBLs) was 100%, and the blaTEM gene was predominant in all of the isolates. In conclusion, our results identify the mechanism of quinolone resistance for the first time and reveal the prevalence of integron and ESBLs in E. coli isolates from dairy cattle with bovine endometritis in China after 20 years of quinolone usage in cattle. PMID- 24224498 TI - Positive HBV-NAT in a blood donor 11 years after HBV vaccination. PMID- 24224499 TI - Basic processes in reading aloud and colour naming: towards a better understanding of the role of spatial attention. AB - Whether or not lexical access from print requires spatial attention has been debated intensively for the last 30 years. Studies involving colour naming generally find evidence that "unattended" words are processed. In contrast, reading-based experiments do not find evidence of distractor processing. One theory ascribes the discrepancy to weaker attentional demands for colour identification. If colour naming does not capture all of a subject's attention, the remaining attentional resources can be deployed to process the distractor word. The present study combined exogenous spatial cueing with colour naming and reading aloud separately and found that colour naming is less sensitive to the validity of a spatial cue than is reading words aloud. Based on these results, we argue that colour naming studies do not effectively control attention so that no conclusions about unattended distractor processing can be drawn from them. Thus we reiterate the consistent conclusion drawn from reading aloud and lexical decision studies: There is no word identification without (spatial) attention. PMID- 24224500 TI - Face, content, construct and concurrent validity of dry laboratory exercises for robotic training using a global assessment tool. AB - OBJECTIVES: To evaluate robotic dry laboratory (dry lab) exercises in terms of their face, content, construct and concurrent validities. To evaluate the applicability of the Global Evaluative Assessment of Robotic Skills (GEARS) tool to assess dry lab performance. MATERIALS AND METHODS: Participants were prospectively categorized into two groups: robotic novice (no cases as primary surgeon) and robotic expert (>=30 cases). Participants completed three virtual reality (VR) exercises using the da Vinci Skills Simulator (Intuitive Surgical, Sunnyvale, CA, USA), as well as corresponding dry lab versions of each exercise (Mimic Technologies, Seattle, WA, USA) on the da Vinci Surgical System. Simulator performance was assessed by metrics measured on the simulator. Dry lab performance was blindly video-evaluated by expert review using the six-metric GEARS tool. Participants completed a post-study questionnaire (to evaluate face and content validity). A Wilcoxon non-parametric test was used to compare performance between groups (construct validity) and Spearman's correlation coefficient was used to assess simulation to dry lab performance (concurrent validity). RESULTS: The mean number of robotic cases experienced for novices was 0 and for experts the mean (range) was 200 (30-2000) cases. Expert surgeons found the dry lab exercises both 'realistic' (median [range] score 8 [4-10] out of 10) and 'very useful' for training of residents (median [range] score 9 [5-10] out of 10). Overall, expert surgeons completed all dry lab tasks more efficiently (P < 0.001) and effectively (GEARS total score P < 0.001) than novices. In addition, experts outperformed novices in each individual GEARS metric (P < 0.001). Finally, in comparing dry lab with simulator performance, there was a moderate correlation overall (r = 0.54, P < 0.001). Most simulator metrics correlated moderately to strongly with corresponding GEARS metrics (r = 0.54, P < 0.001). CONCLUSIONS: The robotic dry lab exercises in the present study have face, content, construct and concurrent validity with the corresponding VR tasks. Until now, the assessment of dry lab exercises has been limited to basic metrics (i.e. time to completion and error avoidance). For the first time, we have shown it is feasibile to apply a global assessment tool (GEARS) to dry lab training. PMID- 24224501 TI - Langerhans cell disease of the eyelids masquerading as blepharochalasis. AB - Langerhans cell disease (LCD) occurring as an isolated tumor of the eyelids has been described infrequently. Moreover, none of the reported cases had associated systemic involvement. We present an unusual case of LCD of the eyelids masquerading as blepharochalasis with central diabetes insipidus (CDI). PMID- 24224502 TI - Breast care in the transgender individual. AB - INTRODUCTION: Transgender individuals undergo hormone therapy and/or alter their breasts or genitals to facilitate a transition from male to female or female to male. Changes in the breast tissue from hormone therapy, breast binding, mastectomy, or breast augmentation are of specific interest to women's health care providers. To provide competent care, providers must be knowledgeable about unique aspects of breast health in this vulnerable population, including screening guidelines and client education. The purpose of this integrative literature review is to compile the current research on breast health for transgender individuals and to serve as a resource for providers. METHODS: A search of the literature was performed using CINAHL, Ovid, and PubMed. Results were reviewed for relevant articles, and the reference lists of these were reviewed for additional resources. When available, studies specific to the transgender population are presented; studies of other populations are also included when relevant. Theories of human endocrinology, physiology, and anatomy will provide the foundation for the review and discussion. RESULTS: Research into breast care for transgender individuals is limited. Often, practitioners must draw conclusions for practice from scattered case studies or research with nontransgender populations. Many of the procedures and practices transgender individuals choose to undergo, such as implantation, injection, binding, and mastectomy, carry serious risks. DISCUSSION: Transgender individuals should be counseled on all the possible outcomes of their decisions, so they are capable of making informed choices. They must also be followed with careful consideration of these choices. More research in many areas of transgender breast care is necessary. PMID- 24224503 TI - Omega-3 fatty acids: a potential future treatment for asthma? PMID- 24224505 TI - Respiratory failure due to blastomycosis infection in a patient with hypertension, cirrhosis and chronic pancreatitis. AB - Blastomycosis is an endemic fungal infection in North America. It usually causes acute and occasionally chronic pneumonias with disseminated infection, particularly skin lesion, as an extrapulmonary manifestation. Many cases are asymptomatic; however, a few patients progress to develop severe pulmonary infection leading to acute respiratory distress syndrome, which carries a high mortality rate. Disseminated blastomycosis involving the heart is exceptionally rare and can be potentially life threatening. To our knowledge, there are only four reported cases of cardiac blastomycosis in the literature. Here, we report a case of cardiac blastomycosis who initially presented with respiratory failure. In our patient, it was practically impossible to establish a diagnosis of cardiac blastomycosis antemortem because of his previous cardiac history related to alcoholic cardiomyopathy, which confounded the cardiac findings. This case raises an important issue of clinically considering involvement of the heart in cases of disseminated blastomycosis. Perhaps if the patient did not have a prior cardiac history, a new onset heart failure may have suggested cardiac involvement. PMID- 24224506 TI - Tai Chi as a form of exercise training in people with chronic obstructive pulmonary disease. AB - Tai Chi is an ancient Chinese martial art which incorporates elements of strengthening, balance, postural alignment and concentration. The benefits of Tai Chi in the healthy population have been widely examined. In comparison, only three studies have evaluated the effects of Tai Chi in people with chronic obstructive pulmonary disease (COPD). Existing evidence suggests that the exercise intensity of Tai Chi reaches a moderate level in people with COPD. Furthermore, a short-term program of Tai Chi improves exercise capacity, health related quality of life, balance and quadriceps strength in people with mild to moderate COPD. More studies are warranted to examine the effects of different styles of Tai Chi and the long-term benefits of Tai Chi as an exercise regimen for people with COPD. PMID- 24224507 TI - Measurement of physical activity in patients with cystic fibrosis: a systematic review. AB - Physical activity (PA) improves exercise capacity, slower decline in lung function and improve quality of life in patients with cystic fibrosis (CF). Despite the importance of PA, it is important to assess the amount of PA. The objective of this literature review was to evaluate the validity and usability of instruments that are used to measure PA in patients with CF. GoogleScholar, ScienceDirect, The Cochrane Library and PUBMED database were searched. All studies that included instruments to measure PA of patients with CF, published from 2000 till June 2012 were reviewed. Eight studies were included in this systematic review. At this moment, there is not sufficient evidence to support incorporation of specific tools to facilitate the PA assessment into clinical practice. Pedometers may offer an inexpensive method of obtaining a measurement of PA, and there is some evidence for supporting its use in CF. PMID- 24224508 TI - The usefulness of the mannitol challenge test for asthma. AB - The mannitol test was developed as an easy-to-use, safe, standardized bronchial challenge test for diagnosing asthma in a wide range of clinical settings. The mannitol test has a moderate sensitivity and will only detect approximately 60% of asthma cases. Hence, a negative mannitol test cannot be used to rule out asthma. The advantage of the mannitol test is a high specificity. In an individual with symptoms suggestive of asthma, a positive test indicates a high likelihood of asthma with ongoing airway inflammation and seems useful for detecting asthma requiring regular anti-inflammatory therapy. In this review, the current knowledge on the usefulness of the mannitol in a clinical setting as well as in clinical trials is presented and outstanding questions on the usefulness of the test are discussed. PMID- 24224509 TI - Aerosol therapy in children: challenges and solutions. AB - Using aerosolized medications for the treatment of children has gained importance over the years. However, aerosol drug delivery to infants and pediatrics is not an easy task as it has been influenced by many challenges. Most aerosol devices have been designed for use in adults not for children. Therefore, they require some critical assessment in device selection and often a level of adaptation for use with smaller children. It is well documented that each aerosol device and interface that have been used for the treatment of children has its own advantages and challenges in drug delivery. This paper provides a comprehensive review of dosing, drug-device combination, aerosol devices and interfaces used for drug delivery to children with pulmonary diseases. Solutions to the challenges with the aim of optimizing aerosol therapy in this patient population are also discussed. PMID- 24224510 TI - Advances in airway clearance technologies for chronic obstructive pulmonary disease. AB - Techniques to promote clearance of sputum from the airways (airway clearance techniques; ACTs) have existed in clinical practice for more than a century. This review examines current evidence and clinical recommendations regarding ACTs for individuals with chronic obstructive pulmonary disease. Comparisons between this literature and reports of current practice suggest that discrepancies may exist in relation to the clinical management of sputum in individuals with COPD. The novel application of newer technologies has enhanced our ability to assess the complex physiological processes underpinning airway clearance therapy. The potential for physiologically tailored ACT prescription may, however, depend on the capacity for translation of such technology from the research setting into the clinical environment. Future directions regarding this common form of therapy will be discussed, including identification of the key research priorities to optimize evidence-based practice in this area. PMID- 24224512 TI - Female receptivity and secondary traumatization in the family. AB - This paper addresses the question of gendered receptivity to Secondary Traumatic Syndrome (STS) in the family. Unlike other manifestations of distress in the family, where gender comparisons are a matter of course, very few such comparisons are made in studies of STS. Review of the findings of 12 studies, the only studies, to date, that provide data enabling the comparison of STS in males and females, shows that females in the family, whether daughters, wives, or mothers, are consistently more likely than the males, whether sons, husbands, or fathers, to experience the Posttraumatic Stress Disorder (PTSD) symptoms of a traumatized family member without having experienced the traumatic event itself. This pattern pertains to whether the event that precipitated the primary trauma was a collective or individual trauma and whether the STS sufferer was a child or adult or living or not living with the PTSD casualty. The Discussion points out that gender is an important factor in the development of STS, whether in interaction with role, beyond role, or both. PMID- 24224513 TI - Loss of endoplasmic reticulum calcium pump expression in choroid plexus tumours. AB - AIMS: Sarco/Endoplasmic Reticulum Calcium ATPase-type calcium pumps (SERCA enzymes) control cell activation by sequestering calcium ions from the cytosol into the endoplasmic reticulum. Although endoplasmic reticulum calcium signalling plays an important role in the regulation of choroid plexus epithelial function, SERCA expression in the choroid plexus has not been investigated so far. METHODS: In this work we investigated the expression of the SERCA3-type calcium pump in choroid plexus epithelial cells grown in vitro, and in normal and hyperplastic choroid plexus tissue, in choroid plexus papillomas displaying various degrees of atypia, and in choroid plexus carcinoma by immunohistochemistry in situ. RESULTS: Whereas normal choroid plexus epithelial cells express SERCA3 abundantly, SERCA3 expression is strongly decreased in papillomas, and is absent in choroid plexus carcinoma, while expression in hyperplastic epithelium is high, similarly to normal epithelium. SERCA3 expression was detected also in normal primary choroid plexus epithelial cells grown in vitro, and expression was markedly enhanced by short-chain fatty acid-type cell differentiation inducing agents, including valproate. CONCLUSION: These observations show that SERCA3 is a new phenotypic marker of normal choroid plexus epithelial differentiation, and that SERCA3 constitutes an early tumour marker 'by loss of expression' in the choroid plexus that may be useful to distinguish hyperplastic processes from papillomas. Endoplasmic reticulum calcium homeostasis becomes anomalous, due to loss of SERCA3 expression, already in benign neoplastic lesions of the choroid plexus epithelium. PMID- 24224514 TI - Immunohistochemical localization of connective tissue growth factor, transforming growth factor-beta1 and phosphorylated-smad2/3 in the developing periodontium of rats. AB - BACKGROUND AND OBJECTIVE: Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta1 (TGF-beta1), and TGF-beta1-induced CTGF expression is regulated through the SMAD pathway. CTGF is implicated in the development of cartilage, bone and tooth. However, its expression in the developing periodontium is unclear. Therefore, we aimed to investigate the immunolocalization of CTGF, TGF-beta1 and phosphorylated SMAD2/3 (pSMAD2/3) in the developing periodontium of rats. MATERIAL AND METHODS: The maxillaries of Wistar rats, 2, 3, 7 and 12 wk of age, were used and the localization of CTGF, TGF-beta1 and pSMAD2/3 was detected using immunoperoxidase techniques. RESULTS: Hertwig' s epithelial root sheath (HERS) cells were strongly positive for CTGF and TGF-beta1, but not for pSMAD2/3. Positive staining for CTGF, TGF-beta1 and pSMAD2/3 was found in bone and periodontal ligament. In cementum, most cementoblasts associated with cellular cementum and some cementocytes stained strongly for CTGF, whereas cementoblasts associated with acellular cementum did not express CTGF. No signal for TGF-beta1 was observed in cellular and acellular cementum. In addition, most cementocytes were strongly positive for pSMAD2/3. CONCLUSION: CTGF, TGF-beta1 and pSMAD2/3 are localized in bone and periodontal ligament, but are differentially expressed in HERS and cementum. The results of our study indicate that the regulation of CTGF expression by TGF-beta1 might be cell-type specific in periodontium. PMID- 24224515 TI - The sedative effects and the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation in pediatric patients: a randomized comparison between two different doses of preoperative intranasal dexmedetomidine. AB - OBJECTIVE: Premedication with intranasal dexmedetomidine (DEX) has shown to be an effective sedative in pediatric patients. This prospective, randomized, and controlled investigation was designed to evaluate whether the difference in intranasal DEX dosing would produce different beneficial effects on the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation. METHODS: Forty children, aged from 3 to 6 years, of American Society of Anesthesiologists physical status I or II and scheduled for elective adenotonsillectomy randomly received intranasal DEX 1 MUg.kg(-1) (group D1) or 2 MUg.kg(-1) (group D2) 30 min before anesthesia induction. Anesthesia was induced with sevoflurane in oxygen flow. Mean arterial pressure (MAP) and heart rate (HR) as measurements of cardiovascular response and bispectral index (BIS) as an index of arousal response were recorded every 5 min after intranasal DEX administration and measured every 1 min for 5 min after intubation. Sedation status, behavior scores, and mask induction scores were also assessed. RESULTS: Mean arterial pressure did not show statistical differences during the anesthesia induction, but did demonstrate significantly milder responses to laryngoscopy and intubation in group D2 compared with group D1. Change in HR was consistent with MAP during laryngoscopy and intubation. Patients who received 2 MUg.kg(-1) DEX presented with deeper sedation and less anxiety by the assessments of the alertness scale, behavior score, and BIS scores. Group D2 dosing achieved more favorable scores in children undergoing mask induction. CONCLUSION: Intranasal DEX 2 MUg.kg(-1) administered 30 min before anesthesia induction provides considerable effect to attenuate the increase in MAP caused by intubation response. Changes in HR and BIS also demonstrate that this kind of premedication provides effective attenuation of intubation response. And preoperative intranasal DEX 2 MUg.kg(-1) produces optimal-sedation, more favorable anesthesia induction course in pediatric patients. Premedication of intranasal DEX is a considerable way to blunt cardiovascular and arousal responses to endotracheal intubation. PMID- 24224516 TI - Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. AB - IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA-matched sibling donor. We could achieve engraftment and regimen-related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor-derived Tregs and disappearance of anti-villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor-derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs. PMID- 24224517 TI - In vivo evidence of an age-related increase in ATP cost of contraction in the plantar flexor muscles. AB - Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered haemodynamic response to exercise in the elderly. Thus we examined whether (i) the ATP cost of contraction increases with age, and (ii) this results in altered convective O(2) delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining (31)P-MRS (magnetic resonance spectroscopy), Doppler ultrasound imaging and NIRS (near-IR spectroscopy) during dynamic plantar flexion exercise at 40% of WR(max) (maximal power output) in 20 healthy young and 20 older subjects matched for physical activity. The ATP cost of contraction was significantly higher in the old (7.2+/-4.1 mM/min per W) compared with the young (2.4+/-1.9 mM/min per W; P<0.05) and this was only significantly correlated with the plantar flexion WR(max) value in the old subjects (r=-0.52; P<0.05). Even when differences in power output were taken into account, end-exercise blood flow (old, 259+/-168 ml/min per W and young, 134+/-40 ml/min per W; P<0.05) and convective O(2) delivery (old, 0.048+/-0.031 l/min per W and young, 0.026+/-0.008 l/min per W; P<0.05) were greater in the old in comparison with the young subjects. In contrast, the NIRS oxyhaemoglobin, deoxyhaemoglobin and microvascular oxygenation indices were not significantly different between the groups (P>0.05). Therefore the present study reveals that, although the peripheral haemodynamic responses to plantar flexion exercise appear to be appropriate, the elevated energy cost of contraction and associated reduction in the WR(max) value in this muscle group may play a role in limiting exercise capacity with age. PMID- 24224518 TI - Extrahepatic stem cells mobilized from the bone marrow by the supplementation of branched-chain amino acids ameliorate liver regeneration in an animal model. AB - BACKGROUND AND AIMS: In recent years, bone marrow (BM)-derived stem cell repopulation of injured organs has been increasingly observed; however, the extent to which it occurs and its clinical relevance remain unclear. Here, we investigated on the potential of extrahepatic stem cells to become hepatocytes using the treatment of the oral supplementation of branched-chain amino acids (BCAA). METHODS: In the first, Sprague-Dawley (SD) rats were administered BCAA to promote liver regeneration; in the second, syngenic liver transplantations using wild-type SD rats that do not express green fluorescent protein (GFP) as syngenic donors and GFP-transgenic SD rats as recipients to confirm that an extrahepatic source of cells (GFP(+)) could repopulate the transplanted (GFP(-)) liver were performed. RESULTS: Treatment of the oral supplementation of BCAA for 2-3 weeks before transplantation to promote liver regeneration resulted in greater than 7 days graft volume, with extensive spotty conversion of a small wild-type graft to the recipient GFP(+) genotype. The treatment by oral supplementation of BCAA resulted in higher levels of CD34+SDF+c-kit+ stem cells in the blood and liver after liver transplantation. Liver repopulation could be achieved with hepatocytes that bone marrow-derived from stem cells proliferated. CONCLUSIONS: We have identified extrahepatic stem cell migration from the BM to the injured liver as a mechanism underlying liver regeneration that supports hepatocyte proliferation in diseased liver. Our results suggested that BCAA is able to mobilize a population of BM-derived cells that contribute to hepatic regeneration. PMID- 24224519 TI - Topical cholesterol treatment ameliorates hapten-evoked cutaneous hypersensitivity by sustaining expression of 11beta-HSD1 in epidermis. AB - Changes in the stratum corneum extracellular matrix impair epidermal barrier function and may cause dermatoses. The aim of this study was to examine the effect of exogenous cholesterol application on skin barrier function and cutaneous inflammation. Skin barrier-disrupted or hapten-stimulated mice were treated with topical cholesterol. The effect of topical cholesterol application on an oxazolone (OXA)-induced hypersensitivity reaction was evaluated. Topical application of cholesterol efficiently decreased transepidermal water loss in areas of barrier-disrupted skin and ameliorated OXA-induced cutaneous hypersensitivity. These favourable effects may have resulted from sustained expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the cholesterol-treated skin. As 11beta-HSD1 is known to produce active cortisol, topical cholesterol may attenuate contact hypersensitivity by normalizing secretion of hormonally active cortisol from the skin. PMID- 24224520 TI - On the morphology of the digestive system of two Monomorium ant species. AB - The digestive system of adults and mature larvae of two ant species of Monomorium Mayr (Hymoneptera: Formicidae) were described with the aid of light and scanning electron microscopy, as there is a lack of studies in this area. These two ant species are recurrently found in urban habitats and are known as 'tramp species,' as they cause problems in households, businesses, and hospitals. The most interesting finds of the present study include the existence of spinules in the crop of adults, and the number of Malpighian tubules and rectal pads was constant among different castes, ages, and species. PMID- 24224521 TI - Rationale and methodology for a multicentre randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes. AB - BACKGROUND: Submassive pulmonary embolism (PE) has a low mortality rate but can degrade functional capacity. OBJECTIVE: The present study aims to provide rationale, methodology, and initial findings of a multicentre, randomised trial of fibrinolysis for PE that used a composite end-point, including quality of life measures. METHODS: This investigator-initiated study was funded by a contract between a corporate partner and the investigator's hospital (the prime site). The investigator was the Food and Drug Administration (FDA) sponsor. The prime site subcontracted, indemnified, and trained consortia members. Consenting, normotensive patients with PE and right ventricular strain (by echocardiography or biomarkers) received low-molecular-weight heparin and random assignment to a single bolus of tenecteplase or placebo in double-blinded fashion. The outcomes were: (i) in-hospital rate of intubation, vasopressor support, and major haemorrhage, or (ii) at 90 days, death, recurrent PE, or composite that defined poor quality of life (echocardiography, 6 min walk test and surveys). The planned sample size was n = 200. RESULTS: Eight sites enrolled 87 patients over 5 years. The ratio of patients screened for each enrolled was 7.4 to 1, equating to 11 h screening time per patient enrolled. Primary barrier to enrolment was the cost of screening. Two patients died (2.5%, 95%CI [0-8%]), one developed shock, but 18 (22%, 95%CI: [13-30%]) had a poor quality of life. CONCLUSIONS: An investigator initiated, FDA-regulated, multicentre trial of fibrinolysis for submassive PE was conducted, but was limited by screening costs and a low mortality rate. Quality of life measurements might represent a more important patient-centred end-point. PMID- 24224522 TI - Controlling the dipole-dipole interactions between terbium(III) phthalocyaninato triple-decker moieties through spatial control using a fused phthalocyaninato ligand. AB - Using a fused phthalocyaninato ligand to control the spatial arrangement of Tb(III) moieties in Tb(III) single-molecule magnets (SMMs), we could control the dipole-dipole interactions in the molecules and prepared the first tetranuclear Tb(III) SMM complex. [Tb(obPc)2]Tb(Fused-Pc)Tb[Tb(obPc)2] (abbreviated as [Tb4]; obPc = 2,3,9,10,16,17,23,24-octabutoxyphthalocyaninato, Fused-Pc = bis{7(2),8(2),12(2),13(2),17(2),18(2)-hexabutoxytribenzo[g,l,q]-5,10,15,20 tetraazaporphirino}[b,e]benzenato). In direct-current magnetic susceptibility measurements, ferromagnetic interactions among the four Tb(3+) ions were observed. In [Tb4], there are two kinds of magnetic dipole-dipole interactions. One is strong interactions in the triple-decker moieties, which dominate the magnetic relaxations, and the other is the weak one through the fused phthalocyaninato (Pc) ligand linking the two triple-decker complexes. In other words, [Tb4] can be described as a weakly ferromagnetically coupled dimer of triple-decker Tb2(obPc)3 complexes with strong dipole-dipole interactions in the triple-decker moieties and weak ones through the fused phthalocyaninato ligand linking the two triple-decker complexes. For [Tb4], dual magnetic relaxation processes were observed similar to other dinuclear Tb(III)Pc complexes. The relaxation processes are due to the anisotropic centers. This is clear evidence that the magnetic relaxation mechanism depends heavily on the dipole-dipole (f-f) interactions between the Tb(3+) ions in the systems. Through a better understanding of the magnetic dipole-dipole interactions obtained in these studies, we have developed a new strategy for preparing Tb(III) SMMs. Our work shows that the SMM properties can be fine-tuned by introducing weak intermolecular magnetic interactions in a controlled SMM spatial arrangement. PMID- 24224523 TI - Pharmacokinetics in foremilk and antimicrobial activity of cephapirin following intramammary administration in healthy and Staphylococcus aureus-infected cows. AB - AIM: To evaluate the kinetic profile of cephapirin and detect differences in its milk disposition following intramammary administration in healthy, and subclinically Staphylococcus aureus infected, quarters of lactating cows, to assess the minimum inhibitory concentration (MIC) of cephapirin for Staph. aureus field isolates, and to calculate the time during which drug concentrations were above the MIC (T>MIC). METHODS: Five healthy and five Staph. aureus-infected lactating cows received cephapirin at 275 mg/quarter, twice at 12-hour intervals. Foremilk samples were manually collected from individual quarters before treatments and 2, 8, 12 hours after the last drug administration, and then every 12 hours until the tenth milking. Concentrations of cephapirin and desacetyl cephapirin were measured in milk samples after solid phase extraction and high performance liquid chromatography analysis. A non-compartmental model was applied to data to obtain pharmacokinetic results. Eleven Staph. aureus isolates from the study-infected quarters and 30 additional isolates from cows in another two farms in the same area were used to determine MIC for cephapirin using the microdilution broth method. RESULTS: Mean maximum drug concentrations were higher in milk from healthy quarters (1334.8 (SD 1322.7) ug/mL) than in the infected ones (234.7 (SD 141.4) ug/mL), but the elimination half-life was longer in the infected (4.8 (SD 1.9) hours) than uninfected (3.3 (SD 0.33) hours) quarters (p<0.05). Mean residence time was comparable in healthy and infected quarters (approximately 8 hours). The amounts of desacetyl-cephapirin recovered in the samples were very low (below 2%). The MIC90 for all field strains of Staph. aureus (n=41) was 0.25 MUg/mL. The calculated T>MIC90 was 38 (SD 13), 27 (SD 11) and 35 (SD 8) hours after last treatment in healthy, suspected and infected quarters, respectively. CONCLUSION AND CLINICAL RELEVANCE: The intramammary administration of sodium cephapirin at 275 mg/quarter, twice every 12 hours in lactating cows resulted in higher drug concentrations in milk of quarters with no infection than in the subclinically infected ones. These concentrations were above the MIC90 for 35 hours in infected cows. According to these results intramammary administration of cephapirin at 12-hour intervals during lactation should be potentially effective against Staph. aureus infection, but studies of clinical efficacy are necessary for confirmation. PMID- 24224524 TI - Transparent superhydrophobic/translucent superamphiphobic coatings based on silica-fluoropolymer hybrid nanoparticles. AB - This paper describes a simple approach to prepare a transparent superhydrophobic coating and a translucent superamphiphobic coating via spraying silica fluoropolymer hybrid nanoparticles (SFNs) without any pre- or post-treatment of substrates; these nanoparticles create both microscale and nanoscale roughness, and fluoropolymer acts as a low surface energy binder. We also demonstrate the effects of varying the concentration of the SFN sol on the water and hexadecane repellency and on the transparency of the coated glass substrates. An increase in the concentration of the sol facilitates the transition between the superhydrophobic/transparent and superamphiphobic/translucent states. This transition results from an increase in the discontinuities in the three-phase (solid-liquid-gas) contact line and in the light scattering properties due to micropapillae tuned by varying the concentration of the sol. This versatile and controllable approach can be applied to a variety of substrates over large areas and may provide a wide range of applications for self-cleaning coatings of optoelectronics, liquid-repellent coatings, and microfluidic systems. PMID- 24224525 TI - Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis. AB - AIMS: Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function. RESULTS: Long-term dietary supplementation with sodium nitrate (0.1 and 1 mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose. INNOVATION AND CONCLUSIONS: These results demonstrate the existence of a cross talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis. PMID- 24224527 TI - Bio-inspired polydopamine: a versatile and powerful platform for covalent synthesis of molecular sieve membranes. AB - Inspired by the bioadhesive ability of the marine mussel, a simple, versatile, and powerful synthesis strategy was developed to prepare highly reproducible and permselective molecular sieve membranes by using polydopamine as a novel covalent linker. Attributing to the formation of strong covalent and noncovalent bonds, ZIF-8 nutrients are attracted and bound to the support surface, thus promoting the ZIF-8 nucleation and the growth of uniform, well intergrown, and phase-pure ZIF-8 molecular sieve membranes. The developed ZIF-8 membranes show high hydrogen selectivity and thermal stability. At 150 degrees C and 1 bar, the mixture separation factors of H2/CO2, H2/N2, H2/CH4, and H2/C3H8 are 8.9, 16.2, 31.5 and 712.6, with H2 permeances higher than 1.8 * 10(-7) mol.m(-2).s(-1).Pa(-1), which is promising for hydrogen separation and purification. PMID- 24224526 TI - Model combustion-generated particulate matter containing persistent free radicals redox cycle to produce reactive oxygen species. AB - Particulate matter (PM) is emitted during thermal decomposition of waste. During this process, aromatic compounds chemisorb to the surface of metal-oxide containing PM, forming a surface-stabilized environmentally persistent free radical (EPFR). We hypothesized that EPFR-containing PM redox cycle to produce ROS and that this redox cycle is maintained in biological environments. To test our hypothesis, we incubated model EPFRs with the fluorescent probe dihydrorhodamine (DHR). Marked increases in DHR fluorescence were observed. Using a more specific assay, hydroxyl radicals ((*)OH) were also detected, and their level was further increased by cotreatment with thiols or ascorbic acid (AA), known components of epithelial lining fluid. Next, we incubated our model EPFR in bronchoalveolar lavage fluid (BALF) or serum. Detection of EPFRs and (*)OH verified that PM generate ROS in biological fluids. Moreover, incubation of pulmonary epithelial cells with EPFR-containing PM increased (*)OH levels compared to those in PM lacking EPFRs. Finally, measurements of oxidant injury in neonatal rats exposed to EPFRs by inhalation suggested that EPFRs induce an oxidant injury within the lung lining fluid and that the lung responds by increasing antioxidant levels. In summary, our EPFR-containing PM redox cycle to produce ROS, and these ROS are maintained in biological fluids and environments. Moreover, these ROS may modulate toxic responses of PM in biological tissues such as the lung. PMID- 24224528 TI - SEM-EDX analysis of brushing abrasion of chitosan and propolis based toothpastes on sound and artificial carious primary enamel surfaces. AB - PURPOSE: The objective of this study was to assess the brushing abrasion effects of toothpastes containing chitosan and propolis on sound and demineralized primary tooth enamel. METHODS: Pairs of enamel specimens were prepared from human extracted primary teeth, embedded in epoxy resin and polished. An artificial subsurface lesion was created in one specimen from each pair. All samples were divided into four groups (Chitodent, Aagaard propolis, Elmex, and Control) and brushed with slurry of toothpastes and artificial saliva in a brushing machine. The brushing abrasion depths were evaluated using computer-guided optical profilometry. RESULTS: No significant differences existed in terms of brushing depths between artificial carious enamel and brushed sound enamel specimens (P>0.05). The abrasion values of the sound enamel samples brushed with Aagaard propolis and control samples were significantly lower than the Elmex group (P<0.05). The lowest brushing abrasion values of demineralized enamel specimens were observed in the Chitodent group (P>0.05). CONCLUSIONS: The tested toothpastes exhibited similar effects in terms of brushing abrasion on both sound and artificially demineralized enamel. Based on mean values without statistical significance, the lowest brushing abrasion values in the demineralized brushed enamel samples were detected in the Chitodent group. PMID- 24224529 TI - Quantitative proteomics reveals significant changes in cell shape and an energy shift after IPTG induction via an optimized SILAC approach for Escherichia coli. AB - Stable isotope labeling by amino acids in cell culture (SILAC) has been widely used in yeast, mammalian cells, and even some multicellular organisms. However, the lack of optimized SILAC media limits its application in Escherichia coli, the most commonly used model organism. We optimized SILACE medium (SILAC medium created in this study for E. coli) for nonauxotrophic E. coli with high growth speed and complete labeling efficiency of the whole proteome in 12 generations. We applied a swapped SILAC workflow and pure null experiment with the SILACE medium using E. coli BL21 (DE3) cells hosting a recombinant plasmid coding for glutathione-S-transferase (GST) and ubiquitin binding domain before and after isopropyl thiogalactoside (IPTG) induction. Finally, we identified 1251 proteins with a significant change in abundance. Pathway analysis suggested that cell growth and fissiparism were inhibited accompanied by the down-regulation of proteins related to energy and metabolism, cell division, and the cell cycle, resulting in the size and shape change of the induced cells. Taken together, the results confirm the development of SILACE medium suitable for efficient and complete labeling of E. coli cells and a data filtering strategy for SILAC-based quantitative proteomics studies of E. coli. PMID- 24224530 TI - Storage time affects umbilical cord blood viability. AB - BACKGROUND: Cryopreserved umbilical cord blood (CB) is increasingly used as a cell source to reconstitute marrow in hematopoietic stem cell transplant patients. Delays in cryopreservation may adversely affect cell viability, thereby reducing their potential for engraftment after transplantation. STUDY DESIGN AND METHODS: The impact of delayed cryopreservation for up to 3 days on the viability of both CD45+ and CD34+ cell populations in 28 CB donations with volumes of 58.40 +/- 15.4 mL (range, 39.4-107.4 mL) was investigated to establish whether precryopreservation storage time could be extended from our current time of 24 to 48 hours in line with other CB banks. Viability was assessed on 3 consecutive days, both before and after cryopreservation, by flow cytometry using 7 aminoactinomycin D (7-AAD) and annexin V methods. RESULTS: The results using 7 AAD and annexin V indicated the viability of CD34+ cells before cryopreservation remained high (>92.33 +/- 4.11%) over 3 days, whereas the viability of CD45+ cells decreased from 86.36 +/- 4.97% to 66.24 +/- 7.78% (p < 0.0001) by Day 3. Storage time significantly affected the viability of CD34+ cells after cryopreservation. Using 7-AAD, the mean CD34+ cell viability decreased by approximately 5% per extra day in storage from 84.30 +/- 6.27% on Day 1 to 79.01 +/- 7.44% (p < 0.0057) on Day 2 and to 73.95 +/- 7.54% (p < 0.0001) on Day 3. With annexin V staining CD34+ cell viability fell by approximately 7% per extra day in storage from 77.17 +/- 8.47% on Day 1 to 69.56 +/- 13.30% (p < 0.0194) on Day 2 and to 62.89 +/- 15.22% (p < 0.0002) on Day 3. CONCLUSION: This study demonstrates that extended precryopreservation storage adversely affects viability and should be avoided. PMID- 24224531 TI - The mismatch between postpartum services and women's needs: Supermom versus lying in. PMID- 24224532 TI - Pyocyanin, a virulence factor produced by Pseudomonas aeruginosa, alters root development through reactive oxygen species and ethylene signaling in Arabidopsis. AB - Pyocyanin acts as a virulence factor in Pseudomonas aeruginosa, a plant and animal pathogen. In this study, we evaluated the effect of pyocyanin on growth and development of Arabidopsis seedlings. Root inoculation with P. aeruginosa PAO1 strain inhibited primary root growth in wild-type (WT) Arabidopsis seedlings. In contrast, single lasI- and double rhlI-/lasI- mutants of P. aeruginosa defective in pyocyanin production showed decreased root growth inhibition concomitant with an increased phytostimulation. Treatment with pyocyanin modulates root system architecture, inhibiting primary root growth and promoting lateral root and root hair formation without affecting meristem viability or causing cell death. These effects correlated with altered proportions of hydrogen peroxide and superoxide in root tips and with an inhibition of cell division and elongation. Mutant analyses showed that pyocyanin modulation of root growth was likely independent of auxin, cytokinin, and abscisic acid but required ethylene signaling because the Arabidopsis etr1-1, ein2-1, and ein3-1 ethylene-related mutants were less sensitive to pyocyanin induced root stoppage and reactive oxygen species (ROS) distribution. Our findings suggest that pyocyanin is an important factor modulating the interplay between ROS production and root system architecture by an ethylene-dependent signaling. PMID- 24224533 TI - The abscisic acid pathway has multifaceted effects on the accumulation of Bamboo mosaic virus. AB - Accepted 29 October 2013. Abscisic acid (ABA) plays a key role in modulating plant responses to different biotic and abiotic stresses. However, the effect of ABA on virus infection is not fully understood. Here, we describe the effects of the ABA pathway on the accumulation of Bamboo mosaic virus (BaMV) and Cucumber mosaic virus (CMV) in two different hosts: Arabidopsis thaliana and Nicotiana benthamiana. We report that ABA2 plays a critical role in the accumulation of BaMV and CMV. Mutants downstream of ABA2 (aao3, abi1-1, abi3-1, and abi4-1) were susceptible to BaMV, indicating that the ABA pathway downstream of ABA2 is essential for BaMV resistance. The aba2-1 mutant decreased the accumulation of BaMV (+)RNA, (-)RNA, and coat protein, with the most dramatic effect being observed for (-)RNA. These findings were further validated by the use of virus induced gene silencing and enzyme-linked immunosorbent assay in N. benthamiana. In addition, infecting N. benthamiana with BaMV or CMV increased ABA contents and activated the SA and ABA pathways, thereby disrupting the antagonism between these two cascades. Our findings uncover a novel role for ABA2 in supporting BaMV and CMV accumulation, distinct from the opposing role of its downstream genes. PMID- 24224534 TI - The Sinorhizobium meliloti EmrAB efflux system is regulated by flavonoids through a TetR-like regulator (EmrR). AB - The divergently oriented Sinorhizobium meliloti emrAB (SMc03168 and SMc03167) and emrR (SMc03169) genes are predicted to encode an efflux system of the major facilitator superfamily and a TetR-like transcriptional regulator, respectively. The transcription of the emrA gene was found to be inducible by flavonoids, including luteolin and apigenin, which are known inducers of the nodulation genes in S. meliloti. Interestingly, quercetin, which does not induce nodulation genes, was also a potent inducer of emrA, indicating that NodD is not directly involved in regulation of emrA. The likely regulator of emrAB is EmrR, which binds to palindrome-like sequences in the intergenic region. Several modifications of the palindromes, including an increase of the spacing between the two half sites, prevented binding of EmrR. Binding was also impaired by the presence of luteolin. Mutations in emrA had no obvious effect on symbiosis. This was in contrast to the emrR mutant, which exhibited a symbiotic deficiency with Medicago sativa. Conserved binding sites for TetR-like regulators within the intergenic regions between the emrAB and emrR genes were identified in many symbiotic and pathogenic members of the order Rhizobiales. PMID- 24224535 TI - Single crystalline InGaAs nanopillar grown on polysilicon with dimensions beyond the substrate grain size limit. AB - Monolithic integration of III-V optoelectronic devices with materials for various functionalities inexpensively is always desirable. Polysilicon (poly-Si) is an ideal platform because it is dopable and semiconducting, and can be deposited and patterned easily on a wide range of low cost substrates. However, the lack of crystalline coherency in poly-Si poses an immense challenge for high-quality epitaxial growth. In this work, we demonstrate, for the first time, direct growth of micrometer-sized InGaAs/GaAs nanopillars on polysilicon. Transmission electron microscopy shows that the micrometer-sized pillars are single-crystalline with pure wurzite-phase, far exceeding the substrate crystal grain size ~100 nm. The high quality growth is enabled by the unique tapering geometry at the base of the nanostructure, which reduces the effective InGaAs/Si contact area to <40 nm in diameter. The small footprint not only reduces stress due to lattice mismatch but also prevents the nanopillar from nucleating on multiple Si crystal grains. This relaxes the grain size requirement for poly-Si, potentially reducing the cost for poly-Si deposition. Lasing is achieved in the as-grown pillars under optical pumping, attesting their excellent crystalline and optical quality. These promising results open up a pathway for low-cost synergy of optoelectronics with other technologies such as CMOS integrated circuits, sensing, nanofluidics, thin film transistor display, photovoltaics, and so forth. PMID- 24224536 TI - The new potential for understanding groundwater contaminant transport. AB - The groundwater remediation field has been changing constantly since it first emerged in the 1970s. The remediation field has evolved from a dissolved-phase centric conceptual model to a DNAPL-dominated one, which is now being questioned due to a renewed appreciation of matrix diffusion effects on remediation. Detailed observations about contaminant transport have emerged from the remediation field, and challenge the validity of one of the mainstays of the groundwater solute transport modeling world: the concept of mechanical dispersion (Payne et al. 2008). We review and discuss how a new conceptual model of contaminant transport based on diffusion (the usurper) may topple the well established position of mechanical dispersion (the status quo) that is commonly used in almost every groundwater contaminant transport model, and evaluate the status of existing models and modeling studies that were conducted using advection-dispersion models. PMID- 24224537 TI - Value learning modulates goal-directed actions. AB - With experience, particular objects can predict good or bad outcomes. This alters our perceptual response to them: Reliable predictors of salient outcomes are recognized faster and better than unreliable predictors, regardless of the value (gain, loss) of the outcome they predict. When attentional resources are constrained, learned value associations matter, causing recognition of gain associated objects to be spared. Here, we ask how learned predictiveness and value change the way we interact with potentially rewarding objects. After associating virtual objects (drinking flutes) with monetary gains or losses, reaching for and grasping corresponding real objects depended on the object's learned value. Action was faster when directed at objects that previously predicted outcomes more rather than less consistently, regardless of value. Conversely, reaches were more direct for gain- than for loss-associated objects, regardless of their predictiveness. Action monitoring thus reveals how value learning components become accessible during action. PMID- 24224538 TI - Quantification of hepatic steatosis: a comparison of the accuracy among multiple magnetic resonance techniques. AB - BACKGROUND AND AIM: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are important diagnostic tools for the non-invasive assessment of hepatic steatosis (HS). This study was conducted to compare different magnetic resonance (MR) techniques and correlate the MR findings with histological and intracellular lipid density findings. METHODS: In this institutional review board approved, Health Insurance Portability and Accountability Act-compliant prospective study, 60 patients scheduled for liver resection were included in this study. Fat fraction in the non-tumorous liver parenchyma was estimated using double-echo MRI, triple-echo MRI (TE-MRI), and MRS. HS was defined by the histologic steatosis percentage (HSP), and intrahepatocellular triglyceride density (IHTGD) of the surgical specimen used as the reference standard. Imaging quantification results were evaluated using Pearson's correlation. Lin's concordance coefficient and Bland-Altman 95% limits of agreement were used to evaluate the concordance of IHTGDs estimated by the three MR techniques. The diagnostic performance was compared using receiver operating characteristic curve analysis. RESULTS: HS assessed by TE-MRI and MRS had a stronger relationship with HS assessed by HSP and IHTGD. The TE-MRI method had the highest concordance correlation coefficients (rho = 0.881) and percentage (95%, 57/60) within the Bland-Altman 95% limits of agreement. Receiver operating characteristic curve analysis for diagnosing > 5% HSP showed significantly larger area under the curve (0.9783) for TE-MRI than for double-echo MRI (0.8773, P = 0.0121). CONCLUSIONS: Among the three MR techniques, TE-MRI and MRS may be the preferred techniques for non-invasive assessment of HS. PMID- 24224539 TI - Therapeutic cancer vaccines: a long and winding road to success. AB - Harnessing the immune system to achieve therapeutic efficacy in cancer has been a milestone in immuno-oncology. Tumor-induced suppression works as an obstacle for the effectiveness of immunotherapies. Advances in our understanding of the interrelationship between cancer immunoediting and immunotherapy led to successful manipulation of anticancer immunity; this provided the platform for combining cancer vaccines with chemotherapies counteracting, to some extent, tumor-induced suppressive entities and demonstrating clinical efficacy. Targeting co-inhibitory and co-stimulatory receptors with immunostimulatory antibodies has also shown clinical promise and its combined use with vaccines is a promising new approach of immunotherapy for cancer. Recent evidence supporting vaccine administration in patients with early and less aggressive disease should be additionally placed to select the appropriate patient population and to identify earlier markers of clinical benefit and immunological parameters that correlate with survival. This review focuses on promising vaccination platforms and essential perspectives in the treatment of cancer. PMID- 24224540 TI - Expression of sarcoplasmic-endoplasmic reticulum Ca-ATPase isoforms in masticatory muscles. AB - The aim of this study was to characterize the sarcoplasmic-endoplasmic reticulum Ca-ATPase (SERCA) isoforms in rabbit masticatory muscles compared with those in fast-twitch muscle. It was hypothesized that combined expression of the SERCA isoforms in fast- and slow-twitch muscles accounts for lower Ca-ATPase activity. SERCA was isolated by differential centrifugation, the isoforms were determined by ELISA, and the activity of each isoform was measured using a colorimetric method. Activity was tested for significance by anova, and the distribution of isoforms was assessed using the chi-square test (P < 0.05) and correlated to SERCA activity using Spearman's rank correlation. SERCA1 was predominant (90.5%) in fast-twitch muscle, whereas a mixture of SERCA isoforms was found in masticatory muscles: 62-78% was SERCA2, 20-37% was SERCA1, and the SERCA3 content was negligible. Depressor muscles showed a significantly higher content (77.8%) of SERCA2, and elevator muscles showed a higher content (35.4%) of SERCA1. Elevator muscles showed higher expression of SERCA2a (58%), and depressor muscles showed higher expression of SERCA2b (20%). The SERCA1 content was mainly SERCA1a and significantly higher for elevator muscles (33%), whereas depressor muscles showed a higher content of SERCA1b (4%). The SERCA1 content of fast-twitch muscle was mainly SERCA1a (88.5%). It is concluded that the mixture of different SERCA isoforms, along with a substantial content of SERCA2b, in masticatory muscles would support lower Ca-ATPase activity and calcium transport. PMID- 24224541 TI - The history of nurse imagery and the implications for recruitment: a discussion paper. AB - AIM: This paper presents a discussion of the history of nurse imagery in the context of recent career choice research and the need for contemporary images for nursing recruitment. BACKGROUND: The critical and growing shortage of nurses is a global concern. Understanding how individuals come to know nursing as a career choice is of critical importance. Stereotypical imaging and messaging of the nursing profession have been shown to shape nurses' expectations and perceptions of nursing as a career, which has implications for both recruitment and retention. DATA SOURCES: Relevant research and literature on nurse imagery in relation to career choice and recruitment were identified through a search of the CINAHL, PsychINFO, Sociological Abstracts, PubMed; Medline and Embase databases from 1970-2012. DISCUSSION: Historical images of nurses and nursing remain prevalent in society today and continue to influence the choice of nursing as a career among the upcoming generation of nurses. Students interested in nursing may be dissuaded from choosing it as a career based on negative, stereotypical images, especially those that position the profession as inferior to medicine. IMPLICATIONS FOR NURSING: Understanding the evolution and perpetuation of popular images and messages in relation to the profession has implications for not only how we recruit and retain future generations of professional nurses but also holds implications for interprofessional collaboration between nursing and other health disciplines. CONCLUSION: Strategies for future recruitment and socialization within the nursing and the health professions need to include contemporary and realistic imaging of both health professional roles and practice settings. PMID- 24224542 TI - Neonatal hyperpigmentation: diagnosis of familial glucocorticoid deficiency with a novel mutation in the melanocortin-2 receptor gene. AB - Familial glucocorticoid deficiency (FGD), a rare autosomal recessive disorder of insensitivity to adrenocorticotropic hormone (ACTH), is characterized by isolated glucocorticoid deficiency and preserved mineralocorticoid production. The clinical features include generalized hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections. Here we describe the case of an infant who exhibited generalized hyperpigmentation and hypoglycemia. A high morning blood ACTH level and low blood cortisol level confirmed the diagnosis of FGD. The patient was found to be homozygous for a novel mutation in the melanocortin-2 receptor gene (635insC, I154H). Early initiation of corticosteroid treatment led to normalization of morning blood ACTH levels and the patient thrived, with subsequent fading of the hyperpigmentation. PMID- 24224543 TI - Detection and correction of assembly errors of rice Nipponbare reference sequence. AB - A complete and high-quality genome reference sequence of an organism provides a solid foundation for a wide research community and determines the outcomes of relevant genomic, genetic, molecular and evolutionary research. Rice is an important food crop and a model plant for grasses, and therefore was the first chosen crop plant for whole genome sequencing. The genome of the japonica representative rice variety, Nipponbare, was sequenced using a gold standard, map based clone-by-clone strategy. However, although the Nipponbare reference sequence (RefSeq) has the best quality for existing crop genome sequences, it still contains many assembly errors and gaps. To improve the Nipponbare RefSeq, first a robust method is required to detect the hidden assembly errors. Through alignments between BAC-end sequences (BESs) embedded in the Nipponbare bacterial artificial chromosome (BAC) physical map and the Nipponbare RefSeq, we detected locations on the Nipponbare RefSeq that were inversely matched with BESs and could therefore be candidates for spurious inversions of assembly. We performed further analysis of five potential locations and confirmed assembly errors at those locations; four of them, two on chr4 and two on chr11 of the Nipponbare RefSeq (IRGSP build 5), were found to be caused by reverse repetitive sequences flanking the locations. Our approach is effective in detecting spurious inversions in the Nipponbare RefSeq and can be applied for improving the sequence qualities of other genomes as well. PMID- 24224544 TI - Inorganic nanoparticle-based drug codelivery nanosystems to overcome the multidrug resistance of cancer cells. AB - Biocompatible inorganic material-based nanosystems provide a novel choice to effectively circumvent the intrinsic drawbacks of traditional organic materials in biomedical applications, especially in overcoming the multidrug resistance (MDR) of cancer cells due to their unique structural and compositional characteristics, for example, high stability, large surface area, tunable compositions, abundant physicochemical multifunctionalities, and specific biological behaviors. In this review, we focus on the recent developments in the construction of inorganic nanoparticles-based drug codelivery nanosystems (mesoporous SiO2, Fe3O4, Au, Ag, quantum dots, carbon nanotubes, graphene oxide, LDH, etc.) to efficiently circumvent the MDR of cancer cells, including the well known codelivery of small molecular anticancer drug/macromolecular therapeutic gene and codelivery of small molecular chemosensitizer/anticancer drug, and very recently explored codelivery of targeting ligands/anticancer drug, codelivery of energy/anticancer drug, and codelivery of contrast agent for diagnostic imaging and anticancer drug. The unsolved issues, future developments, and potential clinical translations of these codelivery nanosystems are also discussed. These elaborately designed biocompatible inorganic materials-based nanosystems offer an unprecedented opportunity and show the encouraging bright future for overcoming the MDR of tumors in clinic personalized medicine and the pharmaceutical industry. PMID- 24224546 TI - Efficacy and complications of intravesical BCG in immunocompromised patients. PMID- 24224545 TI - Knowing prior methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization status increases the empirical use of glycopeptides in MRSA bacteraemia and may decrease mortality. AB - To compare the management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in patients known to be MRSA-colonized/infected (C patients) with the management and outcome in those not known to be colonized/infected (NC-patients), we conducted a 10-year retrospective review of MRSA bacteraemia in an adult tertiary hospital. Clinical data were obtained by chart review, and mortality data from linked databases. Prior MRSA colonization/infection status was available to treating clinicians at the time of the bacteraemia as a 'Micro-Alert' tag on the patient's labels, in medical charts, and in electronic information systems. C-patients accounted for 35.4% of all MRSA bacteraemia episodes. C-patients were more likely to be indigenous, to be diabetic, or to have a history of previous S. aureus infection. Markers of illness severity (Simplified Acute Physiology Score (SAPS)-II, need for admission to the intensive-care unit, length of stay, and metastatic seeding) were similar in both groups. Empirical therapy included a glycopeptide in 49.3% of C-patients vs. 18.9% of NC-patients (p <0.01), and contained an antibiotic to which the MRSA isolate tested susceptible in vitro in 56.7% of C-patients vs. 45.1% of NC patients (p 0.13). All-cause 7-day and 30-day mortality were 7.5% vs. 18.9% (p 0.04), and 22.4% vs. 31.1% (p 0.20), in the C-patient and NC-patient groups, respectively. Knowing MRSA colonization status was significantly associated with lower 30-day mortality in Cox regression analysis (p <0.01). These data suggest that mortality from MRSA bacteraemia is lower in C-patients, which may reflect the earlier use of glycopeptides. The low use of empirical glycopeptides in septic patients known to be previously MRSA-colonized/infected may represent a missed opportunity for infection control to positively impact on clinical management. PMID- 24224547 TI - Modeling the magnetic properties and Mossbauer spectra of multifunctional magnetic materials obtained by insertion of a spin-crossover Fe(III) complex into bimetallic oxalate-based ferromagnets. AB - In this article, we present a theoretical microscopic approach to describe the magnetic and spectroscopic behavior of multifunctional hybrid materials which demonstrate spin crossover and ferromagnetic ordering. The low-spin to high-spin transition is considered as a cooperative phenomenon that is driven by the interaction of the electronic shells of the Fe ions with the full symmetric deformation of the local surrounding that is extended over the crystal lattice via the acoustic phonon field. The proposed model is applied to the analysis of the series [Fe(III)(sal2-trien)] [Mn(II)Cr(III)(ox)3].solv, in short 1.solv, where solv = CH2Cl2, CH2Br2, and CHBr3. PMID- 24224548 TI - Accidental spinal potassium chloride injection successfully treated with spinal lavage. AB - We describe the management of a 62-year-old man who developed severe pain, cramps, paraplegia and pulmonary oedema after the accidental administration of potassium chloride into the subarachnoid space. In addition to supportive treatment, we performed cerebrospinal fluid lavage with saline 0.9%. The patient recovered well without any permanent injury. PMID- 24224549 TI - Treatment of atoxoplasmosis in the Blue-crowned Laughing Thrush (Dryonastes courtoisi). AB - Passerines are frequently parasitized by coccidia, especially species of the genus Isospora, with extra-intestinal stages that can be highly pathogenic causing serious clinical damage in young birds. Whilst there is still no effective treatment to completely clear isosporoid coccidia with extra-intestinal stages from a host species, our results showed that prolonged treatment with toltrazuril (BAYER AG, Leverkusen, Germany) can decrease the oocysts in faeces and thus reduce the extra-intestinal phase of the infection. The toltrazuril treatment is therefore probably indirectly effective against the systemic form of atoxoplasmosis. PMID- 24224550 TI - Genotyping and antimicrobial resistance of Staphylococcus aureus isolates from diseased turkeys. AB - Staphylococcus aureus is a highly versatile pathogen in a large number of domestic animals, including avian species. To gain deeper insight into the epidemiology and diversity of S. aureus associated with articular disease in domestic turkeys, isolates were collected from infected foot joints of turkeys in Brittany (France). A total of 34 isolates were recovered and characterized by means of antimicrobial resistance, staphylococcal protein A typing, macrorestriction pulsed-field gel electrophoresis and micro-array analysis. Thirty isolates were identified as clonal complex (CC) 398 and methicillin susceptible S. aureus (MSSA), one was identified as a methicillin-resistant S. aureus (MRSA) CC398 isolate, and the remaining were also MSSA and belonged to CC5, CC101, and CC121. Eleven different antimicrobial resistance patterns were detected, with most isolates resistant to penicillin and tetracycline. Based on all typing methods used, the 34 isolates could be divided into 22 different strains. Results on selected isolates, genotyped using microarrays, indicated a high homogeneity among pathogenic MSSA isolates from turkeys. Moreover, all isolates, except the unique MRSA isolate, carried specific phiAvbeta prophage avian-niche-specific genes, demonstrating the versatility of S. aureus to adapt to the specific ecological poultry niche. PMID- 24224551 TI - Studies on the presence and persistence of Pasteurella multocida serovars and genotypes in fowl cholera outbreaks. AB - Pasteurella multocida was isolated from poultry on six farms (one free-range duck farm, one free-range turkey farm, one conventional enclosed turkey farm, and three free-range layer farms) suffering fowl cholera outbreaks. In addition, historical isolates from previous outbreaks were available for the conventional turkey farm and the three free-range layer farms. The isolates were serotyped using the Heddleston scheme and genotyped using multi-locus sequencing typing. In the current outbreaks, two of the farms had two different sequence types (STs) of P. multocida in the investigated outbreak (the free-range turkey farm and one of the free-range layer farms). The remaining four farms had one ST within the investigated outbreak. In looking at the historical isolates, two of the four farms had multiple genotypes involved. On the four farms with historical isolates from previous outbreaks, at least one new genotype was present in the investigated outbreak as compared with the historical isolates. On one layer farm, one genotype persisted over a 10-year period. Serotyping revealed the presence of multiple serovars in the current and historical outbreaks, with serovars sometimes changing over time. This study has shown that several STs of P. multocida can be present during some outbreaks of fowl cholera, although other outbreaks involve a single ST. Also, the STs present on a property suffering repeated fowl cholera can both persist and change over time. PMID- 24224552 TI - Carbohydrate diet and reproductive performance of a fruit fly parasitoid, Diachasmimorpha tryoni. AB - Augmentative releases of parasitoid wasps are often used successfully for biological control of fruit flies in programs worldwide. The development of cheaper and more effective augmentative releases of the parasitoid wasp Diachasmimorpha tryoni (Cameron) (Hymenoptera: Braconidae) may allow its use to be expanded to cover Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), a serious pest of many vegetables and most fruit production in Australia. This demands a fuller understanding of the parasitoid's reproductive biology. In this study, mating status, fecundity, and size of female D. tryoni were determined under laboratory conditions. A range of pre-release diets, 10% concentrations of honey, white sugar, and golden syrup, were also assessed in the laboratory. Mature egg loads and progeny yields of mated and unmated parasitoid females were statistically similar, demonstrating that mating status was not a determinant of parasitoid performance. Female lifespan was not negatively impacted by the act of oviposition, though larger females carried more eggs than smaller individuals, indicating a need to produce large females in mass-rearing facilities to maintain this trait. White sugar gave the highest adult female lifespan, while honey and golden syrup shared similar survivorship curves, all significantly greater compared with water control females. Pre-release feeding of D. tryoni, particularly with white sugar, may enhance the impact of released parasitoids on B. tryoni. These findings are important because honey is currently the standard diet for mass-reared braconids, but white sugar is less than one third the cost of other foods; however further work is required to assess postrelease performance of the parasitoid. PMID- 24224553 TI - Review article: evacuating hospitals in Australia: what lessons can we learn from the world literature? AB - The creation of hospitals safe from disaster is an area of increasing public policy. The vulnerability of hospitals to damage and destruction during an event has profound implications for the health of a community. Although hospital evacuations do occur in Australia, their prevalence is unknown and what leads to a successful evacuation is poorly understood. This article reviewed the worldwide hospital evacuation literature to determine the prevalence of hospital evacuations and common precipitants for evacuation. Factors leading to safe evacuation and areas of ongoing challenge were identified. The findings highlight the need for more structured and detailed reporting of hospital responses to disaster. A number of lessons can be learned from hospitals that have experienced evacuation. Most critically, all hospitals must have a practised, detailed hospital evacuation plan existing before an impending threat. There are also areas for improvement in the areas of assessing the risk to the facility, communications, leadership, logistics, staffing and planning. These lessons should be included into comprehensive, detailed evacuation plans for all Australian hospitals, supported by a national framework that standardises planning and response. PMID- 24224555 TI - Toxicity of polyamines and their metabolic products. AB - Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease. PMID- 24224554 TI - Therapists and researchers: advancing collaboration. AB - Collaborative partnerships between community-based clinicians and academic researchers have the potential to improve the relevance, utility, and feasibility of research, as well as the effectiveness of practice. Collaborative partnership research from a variety of fields can inform the development and maintenance of effective partnerships. In this paper we present a conceptual model of research community practice partnership derived from literature across disciplines and then illustrate application of this model to one case example. The case example is a multi-year partnership between an interdisciplinary group of community-based psychotherapists and a team of mental health researchers. This partnership was initiated to support federally funded research on community-based outpatient mental health care for children with disruptive behavior problems, but it has evolved to drive and support new intervention studies with different clinical foci. Lessons learned from this partnership process will be shared and interpreted in the context of the presented research-practice partnership model. PMID- 24224556 TI - Probing adsorption interactions in metal-organic frameworks using X-ray spectroscopy. AB - We explore the local electronic signatures of molecular adsorption at coordinatively unsaturated binding sites in the metal-organic framework Mg-MOF-74 using X-ray spectroscopy and first-principles calculations. In situ measurements at the Mg K-edge reveal distinct pre-edge absorption features associated with the unique, open coordination of the Mg sites which are suppressed upon adsorption of CO2 and N,N'-dimethylformamide. Density functional theory shows that these spectral changes arise from modifications of local symmetry around the Mg sites upon gas uptake and are strongly dependent on the metal-adsorbate binding strength. The expanded MOF Mg2(dobpdc) displays the same behavior upon adsorption of CO2 and N,N'-dimethylethylenediamine. Similar sensitivity to local symmetry is expected for any open metal site, making X-ray spectroscopy an ideal tool for examining adsorption in such MOFs. Qualitative agreement between ambient temperature experimental and 0 K theoretical spectra is good, with minor discrepancies thought to result from framework vibrational motion. PMID- 24224557 TI - In vitro properties of platelets stored in a small container for pediatric transfusion. AB - BACKGROUND: The quality of a platelet (PLT) concentrate (PC) is affected by the number of PLTs in relation to the size and gas permeability of the container. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of PLTs stored in a container of standard or small size. STUDY DESIGN AND METHODS: PCs with 30% plasma and 70% PLT additive solution were prepared from buffy coats. Two PCs were pooled and divided into the following containers: 1 unit and 1/2 a unit into a 1.8-L container (reference container) and 1/2 a unit into a 0.45-L container (test container). In a second set of experiments 1/4 of a unit was stored in the reference and test containers. Swirling, PLT count, blood gases, metabolic variables, PLT activation markers, hypotonic shock response (HSR), and coagulation by free oscillation rheometry were analyzed during 7 days of storage. RESULTS: Swirling was well preserved and pH was acceptable (6.4-7.4) during storage of PLTs in both containers. Glycolysis and PLT activation were higher when storing 1/2 and 1/4 of a unit in the reference container and storage of 1/4 of a unit in the reference container resulted in the largest decrease in HSR. The clotting time was similar whereas the clot elasticity was slightly lower for PLTs when stored as 1/2 and 1/4 of a unit in the reference container. CONCLUSION: Storage of a low number of PLTs benefits by storage in a small container in terms of better maintained in vitro properties. PMID- 24224558 TI - Israeli emergency department nurses' attitudes to an extension of their role and powers. AB - AIMS AND OBJECTIVES: To investigate the opinions of Israeli ED nurses as to (1) an expansion of their powers and autonomy in treating commonly presenting ED conditions, (2) whether nurses or physicians should be responsible for giving ED patients necessary information and (3) whether ED nurses should perform triage. BACKGROUND: The development of the new emergency nurse practitioner role has relieved the pressure on emergency departments, reduced patient waiting times and raised patient satisfaction. Israel has yet to introduce either this role or the triage approach into its emergency departments. DESIGN: This investigation was designed as a cross-sectional study by self-administered questionnaire. METHODS: The researchers distributed a questionnaire they had developed and validated to 270 registered nurses working in 18 general hospital emergency departments. The responses were analysed by chi-square and t-tests and anova. RESULTS: Of respondents 60-90% agreed that they should be granted 10 out of a list of 12 new powers, and a large majority thought nurses should be responsible for performing triage. They wanted to increase the information they gave to patients, both on general ED functioning and on specific medically related matters. CONCLUSIONS: The contribution of this study is the positive response of a large representative sample of ED nurses to extending their powers. It will be necessary to establish postregistration training courses and draw up new regulations reshaping the delivery of emergency medicine. RELEVANCE TO CLINICAL PRACTICE: The study demonstrates that ED nurses are convinced that they need the authority to diagnose and treat commonly presenting ED conditions and perform triage and discharge in order for their department to optimally exploit the resources available to it. The study should promote the development of the emergency nurse practitioner role in Israel and so reduce patient waiting times. PMID- 24224559 TI - How early should obesity prevention start? PMID- 24224560 TI - A recombinant viruslike particle influenza A (H7N9) vaccine. PMID- 24224562 TI - Stereoselective synthesis of P-modified alpha-glycosyl phosphates by the oxazaphospholidine approach. AB - alpha-Glycosyl phosphate derivatives are widely known as constituents of biomolecules. To date, several types of non-natural alpha-glycosyl phosphates including "P-modified analogs" have been synthesized to investigate their characteristics. Herein a new approach to the stereoselective modification of the intersugar phosphorus atom in alpha-glycosyl phosphates by use of the oxazaphospholidine method is presented. Via this approach, the dimers of alpha glycosyl phosphorothioates and alpha-glycosyl boranophosphates were obtained efficiently and stereoselectively. PMID- 24224561 TI - Mercury alters B-cell protein phosphorylation profiles. AB - Environmental exposure to mercury is suggested to contribute to human immune dysfunction. To shed light on the mechanism, we identified changes in the phosphoproteomic profile of the WEHI-231 B cell line after intoxication with Hg(2+). These changes were compared to changes in the phosphoproteome that were induced by pervanadate or okadaic acid exposure. Both 250 MUM HgCl2 and pervanadate, a known phosphotyrosine phosphatase inhibitor, caused an increase in the number of proteins identified after TiO2 affinity selection and LC-MS/MS analysis. Pervanadate treatment had a larger effect than Hg(2+) on the number of Scansite motifs that were tyrosine-phosphorylated, 17, and Ingenuity canonical signaling pathways activated, 4, with score >5.0. However, Hg(2+) had a more focused effect, primarily causing tyrosine-phosphorylation in src homology 2 domains in proteins that are in the B cell receptor signaling pathway. The finding that many of the changes induced by Hg(2+) overlap with those of pervanadate, indicates that at high concentrations Hg(2+) inhibits protein tyrosine phosphatases. PMID- 24224563 TI - Progress in remediation of groundwater at petroleum sites in California. AB - Quantifying the overall progress in remediation of contaminated groundwater has been a significant challenge. We utilized the GeoTracker database to evaluate the progress in groundwater remediation from 2001 to 2011 at over 12,000 sites in California with contaminated groundwater. This paper presents an analysis of analytical results from over 2.1 million groundwater samples representing at least $100 million in laboratory analytical costs. Overall, the evaluation of monitoring data shows a large decrease in groundwater concentrations of gasoline constituents. For benzene, half of the sites showed a decrease in concentration of 85% or more. For methyl tert-butyl ether (MTBE), this decrease was 96% and for TBE, 87%. At remediation sites in California, the median source attenuation rate was 0.18/year for benzene and 0.36/year for MTBE, corresponding to half-lives of 3.9 and 1.9 years, respectively. Attenuation rates were positive (i.e., decreasing concentration) for benzene at 76% of sites and for MTBE at 85% of sites. An evaluation of sites with active remediation technologies suggests differences in technology effectiveness. The median attenuation rates for benzene and MTBE are higher at sites with soil vapor extraction or air sparging compared with sites without these technologies. In contrast, there was little difference in attenuation rates at sites with or without soil excavation, dual phase extraction, or in situ enhanced biodegradation. The evaluation of remediation technologies, however, did not evaluate whether specific systems were well designed or implemented and did not control for potential differences in other site factors, such as soil type. PMID- 24224564 TI - Comment on "prebiotic chemistry within a simple impacting icy mixture". PMID- 24224565 TI - To pass or not to pass: more a question of body orientation than visual cues. AB - This study investigated the influence of pitch body tilt on judging the possibility of passing under high obstacles in the presence of an illusory horizontal self-motion. Seated subjects tilted at various body orientations were asked to estimate the possibility of passing under a projected bar (i.e., a parking barrier), while imagining a forward whole-body displacement normal to gravity. This task was performed under two visual conditions, providing either no visual surroundings or a translational horizontal optic flow that stopped just before the barrier appeared. The results showed a main overestimation of the possibility of passing under the bar in both cases and most importantly revealed a strong influence of body orientation despite the visual specification of horizontal self-motion by optic flow (i.e., both visual conditions yielded a comparable body tilt effect). Specifically, the subjective passability was proportionally deviated towards the body tilt by 46% of its magnitude when facing a horizontal optic flow and 43% without visual surroundings. This suggests that the egocentric attraction exerted by body tilt when referring the subjective passability to horizontal self-motion still persists even when anchoring horizontally related visual cues are displayed. These findings are discussed in terms of interaction between spatial references. The link between the reliability of available sensory inputs and the weight attributed to each reference is also addressed. PMID- 24224566 TI - Forecasting impact injuries of unrestrained occupants in railway vehicle passenger compartments. AB - OBJECTIVE: In order to predict the injury parameters of the occupants corresponding to different experimental parameters and to determine impact injury indices conveniently and efficiently, a model forecasting occupant impact injury was established in this work. METHODS: The work was based on finite experimental observation values obtained by numerical simulation. First, the various factors influencing the impact injuries caused by the interaction between unrestrained occupants and the compartment's internal structures were collated and the most vulnerable regions of the occupant's body were analyzed. Then, the forecast model was set up based on a genetic algorithm-back propagation (GA-BP) hybrid algorithm, which unified the individual characteristics of the back propagation artificial neural network (BP-ANN) model and the genetic algorithm (GA). The model was well suited to studies of occupant impact injuries and allowed multiple parameter forecasts of the occupant impact injuries to be realized assuming values for various influencing factors. Finally, the forecast results for three types of secondary collision were analyzed using forecasting accuracy evaluation methods. RESULTS: All of the results showed the ideal accuracy of the forecast model. When an occupant faced a table, the relative errors between the predicted and experimental values of the respective injury parameters were kept within +/- 6.0 percent and the average relative error (ARE) values did not exceed 3.0 percent. When an occupant faced a seat, the relative errors between the predicted and experimental values of the respective injury parameters were kept within +/- 5.2 percent and the ARE values did not exceed 3.1 percent. When the occupant faced another occupant, the relative errors between the predicted and experimental values of the respective injury parameters were kept within +/- 6.3 percent and the ARE values did not exceed 3.8 percent. CONCLUSIONS: The injury forecast model established in this article reduced repeat experiment times and improved the design efficiency of the internal compartment's structure parameters, and it provided a new way for assessing the safety performance of the interior structural parameters in existing, and newly designed, railway vehicle compartments. PMID- 24224567 TI - Clinical appraisal of the recently proposed Barcelona Clinic Liver Cancer stage B subclassification by survival analysis. AB - BACKGROUND AND AIM: To evaluate the usefulness of Barcelona Clinic Liver Cancer B subclassification (B1-B4) proposed by Bolondi et al. in subjects with hepatocellular carcinoma treated with transarterial chemoembolization according to the current Barcelona Clinic Liver Cancer policy. METHODS: A total of 466 Barcelona Clinic Liver Cancer B patients initially treated with transarterial chemoembolization were included. The subclassification system was tested and modified on the basis of correlation with survival outcomes, which were examined by Kaplan-Meier method and log-rank test. RESULTS: There were 101 (21.7%), 232 (49.8%), 35 (7.5%), and 98 (21.0%) patients in B1, B2, B3, and B4, respectively. There was a significant difference in median survival time between B1 and B2 (41.0 vs 22.1 months, P <= 0.001), and B2 and B3 (22.1 vs 14.1 months, P = 0.004), but not between B3 and B4 (14.1 vs 17.2 months, P = 0.48). We, therefore, developed a modified subclassification, in which B3 subclass was merged with B4 as BIII, and BI and BII corresponded to B1 and B2. The median survival times differed between all three modified subclasses (41.0 vs 22.1 vs 16.6 months, P <= 0.001), and multivariate Cox analysis revealed that the modified Barcelona Clinic Liver Cancer B subclasses independently predicted overall survival (hazard ratios, 1.92 and 2.78 for BII and BIII vs BI; P < 0.001 for each). CONCLUSIONS: The modified subclassification, which divides the Barcelona Clinic Liver Cancer B stage into three substages, would be an effective tool for stratifying this heterogeneous population and facilitating per-subclass-based treatment options. PMID- 24224568 TI - Localized non-conventional renal cell carcinoma: prediction of clinical outcome according to histology. AB - OBJECTIVE: A wide variety of parameters have been investigated in the prognostic significance of non-conventional clear cell renal cell carcinoma. Aim of the present study was to compare its clinical outcome and to determine the independent prognostic factors according to the histology. METHODS: This retrospective study enrolled localized non-conventional clear cell renal cell carcinomas (T1a-T4N0M0), including Xp11.2 translocation (Xp11.2t), all surgically treated in a single institution between 1988 and 2011. The study statistically analyzed the clinicopathological parameters to compare the prognostic outcomes among the different histological subtypes of non-conventional clear cell renal cell carcinoma and to define any independent prognostic factors. RESULTS: A total of 374 cases were examined, including 126 papillary (33.7%), 164 chromophobe (43.9%), eight collecting duct (2.1%), 40 unclassified (10.7%), 16 Xp11.2t (4.3%), seven mucinous tubular and spindle cell (1.8%) renal cell carcinomas and 13 oncocytomas (3.5%). The mean follow up was 56.4 months, with s mean tumor size of 4.9 +/- 3.4 cm. The 4-year recurrence-free survival, overall survival and cancer-specific survival were inversely related to the increase of pathological T stages (P < 0.001). For histological type other than 13 oncocytomas and seven mucinous tubular and spindle cell renal cell carcinomas, the chromophobe showed the best prognosis of survival, followed by papillary, Xp11.2t, unclassified and collecting duct renal cell carcinomas, in this order. All survival rates were significantly different, as according to the histology (P = 0.009). The significant prognostic factors were preoperative body mass index (hazard ratio 0.76), serum albumin (hazard ratio 0.64), T stage (hazard ratio 2.28), the sarcomatoid differentiation (hazard ratio 33.45) and lymphovascular invasion (hazard ratio 12.40) in pathology (P < 0.05). CONCLUSIONS: Different non conventional clear cell renal cell carcinoma subtypes have significantly different clinical characteristics of prognosis with many suggestive predictive factors of survival. PMID- 24224569 TI - Pediatric cutaneous lupus erythematosus treated with pulsed dye laser. AB - Pulsed dye laser (PDL) has been used in adults to treat refractory cutaneous lupus erythematosus (CLE). We report the first case of CLE in a child successfully treated with PDL. PMID- 24224570 TI - Florence Nightingale and Mary Seacole on nursing and health care. AB - AIMS: The purpose of this article is to correct inaccurate information about both Mary Seacole and Florence Nightingale, material that promotes Seacole as a pioneer nurse and heroine, while either ignoring Nightingale or trivializing her contribution. BACKGROUND: Nursing journals have been prominent in promoting inaccurate accounts of the contribution of Seacole to nursing. Some have intermittently published positive material about Nightingale, but none has published redress. DESIGN: Discussion paper. DATA: Primary sources from 1855-2012 were found, which contradict some key claims made about Seacole. Further sources not included here - are identified, with a website reference. IMPLICATIONS FOR NURSING: It is argued that Nightingale remains relevant as a model for nurses, with the many crises in patient care and continuing challenges of hospital safety. CONCLUSION: Greater accuracy and honesty are required in reporting about nursing heroes. Without these, great ideas and examples can be lost to nursing and health care. PMID- 24224571 TI - Interferon-alpha and interferon-gamma modulate Fas-mediated apoptosis in mitomycin-C-resistant human Tenon's fibroblasts. AB - BACKGROUND: The aim of the study was to investigate, using a native mitomycin-C resistant human Tenon's fibroblast cell line, the possibility that interferon alpha and gamma could be used with Fas agonists as an alternative anti-fibrotic strategy to mitomycin-C in trabeculectomy. METHODS: A clinically resistant and in vitro verified mitomycin-C-resistant human Tenon's fibroblast cell line was pretreated with interferon-alpha and interferon-gamma for 48 h before stimulation with an agonistic Fas antibody (CH11) for 2 days to induce cell death. Cell death assays were undertaken. Changes in apoptosis-related proteins were determined by flow cytometry and Western blot. RESULTS: Pretreatment with interferon-alpha or interferon-gamma for 48 h increased Fas, Fas-associated protein with death domain and caspase-8 expression. Protein expression was further increased by combined exposure to interferon-alpha and gamma. Pretreatment with cytokines had no effect on Fas-L and Bcl-2. Interferon-alpha alone did not change the rate of induced cell death. A combination of interferon-alpha and gamma synergistically increased the sensitivity of mitomycin-C-resistant human Tenon's fibroblast cell line to induced cell death. An antagonistic anti-Fas antibody (ZB4) completely blocked induced cell death. Broad caspase inhibitors specific for caspases-8 and -3 reduced induced deaths in interferon pretreated mitomycin-C-resistant human Tenon's fibroblast cell line in a dose-dependent manner. CONCLUSIONS: Interferon alpha and interferon-gamma render mitomycin-C-resistant human Tenon's fibroblast cell line sensitive to Fas-mediated apoptosis. The mechanism involves increased death-inducing signalling complex formation by upregulation of Fas, Fas associated protein with death domain and caspase-8 expression. PMID- 24224572 TI - Unravelling the relationship between degree of disorder and the dissolution behavior of milled glibenclamide. AB - Milling is an attractive method to prepare amorphous formulations as it does not require the use of solvents and is suitable for thermolabile drugs. One of the key critical quality attributes of milled amorphous formulations is their dissolution behavior. However, there are limited studies that have investigated the relationship between degree of disorder induced by milling and dissolution behavior. The main aim of this study was to identify the analytical technique used to characterize degree of disorder that correlates best with the recrystallization behavior during dissolution of milled glibenclamide samples. Solid state and surface changes during dissolution of milled glibenclamide samples were monitored in order to elucidate the processes that influence the dissolution behavior of milled glibenclamide samples. Glibenclamide was ball milled for different durations and analyzed using X-ray powder diffractometry (XRPD), Raman spectroscopy and differential scanning calorimetry (DSC). Recrystallization during dissolution of the milled amorphous materials was investigated using an in situ Raman setup. SEM was used to monitor the surfaces of the compacts during dissolution. XRPD, Raman spectroscopy and DSC indicated that glibenclamide was fully amorphous after milling for 30, 60, and 120 min, respectively. 'DSC amorphous' (i.e. fully amorphous according to the onset of crystallization obtained from DSC) glibenclamide samples experienced negligible recrystallization which had no effect on the dissolution profiles. Samples that were not 'DSC amorphous' experienced recrystallization which resulted in a decrease in dissolution rate. Unexpected elevated dissolution rate was observed initially during dissolution for samples milled for 15 to 45 min, and this was related to particle loss from surfaces of the disks during dissolution. In conclusion, the onset of crystallization obtained from DSC best predicts the recrystallization of glibenclamide during dissolution. Recrystallization and particle loss from the surface of the dissolution should be considered when interpreting the dissolution data of milled glibenclamide samples. PMID- 24224573 TI - Optimization of O3-acyl kojic acid derivatives as potent and selective human neutrophil elastase inhibitors. AB - Human neutrophil elastase (HNE) is an attractive target for treating chronic and acute inflammatory lung diseases. An optimization campaign of the kojic acid scaffold to develop new potent HNE inhibitors is reported. O3-Pivaloyl derivatives were shown to be the most potent inhibitors with IC5o values down to 80 nM. These compounds presented excellent selectivity and cytotoxicity profiles with suitable ligand efficiency. PMID- 24224574 TI - Bias and sensitivity analysis when estimating treatment effects from the cox model with omitted covariates. AB - Omission of relevant covariates can lead to bias when estimating treatment or exposure effects from survival data in both randomized controlled trials and observational studies. This paper presents a general approach to assessing bias when covariates are omitted from the Cox model. The proposed method is applicable to both randomized and non-randomized studies. We distinguish between the effects of three possible sources of bias: omission of a balanced covariate, data censoring and unmeasured confounding. Asymptotic formulae for determining the bias are derived from the large sample properties of the maximum likelihood estimator. A simulation study is used to demonstrate the validity of the bias formulae and to characterize the influence of the different sources of bias. It is shown that the bias converges to fixed limits as the effect of the omitted covariate increases, irrespective of the degree of confounding. The bias formulae are used as the basis for developing a new method of sensitivity analysis to assess the impact of omitted covariates on estimates of treatment or exposure effects. In simulation studies, the proposed method gave unbiased treatment estimates and confidence intervals with good coverage when the true sensitivity parameters were known. We describe application of the method to a randomized controlled trial and a non-randomized study. PMID- 24224575 TI - Clinical trial strategy for penis cancer. PMID- 24224576 TI - Systematic study of the luminescent europium-based nonanuclear clusters with modified 2-hydroxybenzophenone ligands. AB - The reaction of 2-hydroxybenzophenone derivatives with europium ions has afforded a new family of luminescent nonanuclear Eu(III) clusters. Crystal structure analysis of the clusters reveals that the metal core comprises two vertex-sharing square pyramidal units. Most of these complexes show emissions typical of Eu(3+) ion under visible light excitation (400-420 nm) at room temperature. Photophysical characterization and DFT study reveal a correlation between luminescent efficiencies of Eu(III) complexes and the electronic features of the ligands, which can be tuned by the nature of substituents in the 4-position of the ligands. The ligands with a fluorine substituent possess more suitable triplet energy levels, resulting in more intensive luminescence. PMID- 24224577 TI - Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance. AB - We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system. PMID- 24224578 TI - The hockey-stick method to estimate evening dim light melatonin onset (DLMO) in humans. AB - The onset of melatonin secretion in the evening is the most reliable and most widely used index of circadian timing in humans. Saliva (or plasma) is usually sampled every 0.5-1 hours under dim-light conditions in the evening 5-6 hours before usual bedtime to assess the dim-light melatonin onset (DLMO). For many years, attempts have been made to find a reliable objective determination of melatonin onset time either by fixed or dynamic threshold approaches. The here developed hockey-stick algorithm, used as an interactive computer-based approach, fits the evening melatonin profile by a piecewise linear-parabolic function represented as a straight line switching to the branch of a parabola. The switch point is considered to reliably estimate melatonin rise time. We applied the hockey-stick method to 109 half-hourly melatonin profiles to assess the DLMOs and compared these estimates to visual ratings from three experts in the field. The DLMOs of 103 profiles were considered to be clearly quantifiable. The hockey stick DLMO estimates were on average 4 minutes earlier than the experts' estimates, with a range of -27 to +13 minutes; in 47% of the cases the difference fell within +/-5 minutes, in 98% within -20 to +13 minutes. The raters' and hockey-stick estimates showed poor accordance with DLMOs defined by threshold methods. Thus, the hockey-stick algorithm is a reliable objective method to estimate melatonin rise time, which does not depend on a threshold value and is free from errors arising from differences in subjective circadian phase estimates. The method is available as a computerized program that can be easily used in research settings and clinical practice either for salivary or plasma melatonin values. PMID- 24224579 TI - A new algorithm for weekly phenprocoumon dose variation in a southern Brazilian population: role for CYP2C9, CYP3A4/5 and VKORC1 genes polymorphisms. AB - Phenprocoumon is widely used in prophylaxis and treatment of thromboembolic disorders. However, its pharmacokinetics and pharmacodynamics vary according to several genetic and non-genetic factors. Phenprocoumon metabolism is mediated by CYP2C9 and CYP3A enzymes. Moreover, VKORC1 is phenprocoumon target of action. Therefore, the aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP3A4 and CYP3A5 genes with the variance of weekly phenprocoumon dose as well as to develop an algorithm for dose prediction based on genetic and environmental factors. A total of 198 patients with stable phenprocoumon dose, 81% of European ancestry, were investigated. Genotypes were determined by allelic discrimination with TaqMan assays. Polymorphisms -1639G>A and 1173C>T in VKORC1 and the presence of CYP2C9*2 and/or CYP2C9*3 are associated with lower doses. On the other hand, 3730G>A in VKORC1 gene is associated with higher doses. No association was found between CYP3A4*1B, CYP3A5*3 and CYP3A5*6 polymorphisms. Among non-genetic factors, gender, height, age and use of captopril, omeprazole, simvastatin and beta blockers are associated with dose. Two algorithms were derived: one for the whole sample explained 42% of dose variation and one for patients of European ancestry only which explained 46% of phenprocoumon dose. The mean absolute difference between observed and predicted dose was low in both models (3.92 mg/week and 3.54 mg/week, for models 1 and 2, respectively). However, more studies with other genes and environmental factors are needed to test and to improve the algorithm. PMID- 24224580 TI - Success in making Zn+ from atomic Zn(0) encapsulated in an MFI-type zeolite with UV light irradiation. AB - For the first time, the paramagnetic Zn(+) species was prepared successfully by the excitation with ultraviolet light in the region ascribed to the absorption band resulting from the 4s-4p transition of an atomic Zn(0) species encapsulated in an MFI-type zeolite. The formed species gives a specific electron spin resonance band at g = 1.998 and also peculiar absorption bands around 38,000 and 32,500 cm(-1) which originate from 4s-4p transitions due to the Zn(+) species with paramagnetic nature that is formed in MFI. The transformation process (Zn(0) -> Zn(+)) was explained by considering the mechanism via the excited triplet state ((3)P) caused by the intersystem crossing from the excited singlet state ((1)P) produced through the excitation of the 4s-4p transition of an atomic Zn(0) species grafted in MFI by UV light. The transformation process was well reproduced with the aid of a density functional theory calculation. The thus formed Zn(+) species which has the doublet spin state exhibits characteristic reaction nature at room temperature for an O2 molecule having a triplet spin state in the ground state, forming an eta(1) type of Zn(2+)-O2(-) species. These features clearly indicate the peculiar reactivity of Zn(+) in MFI, whereas Zn(0) (H(+))2MFI hardly reacts with O2 at room temperature. The bonding nature of [Zn(2+)-O2(-)] species was also evidenced by ESR measurements and was also discussed on the basis of the results obtained through DFT calculations. PMID- 24224581 TI - CT and MR enterography in children and adolescents with inflammatory bowel disease. AB - The term inflammatory bowel disease (IBD) is used to describe multiple idiopathic disorders of the gastrointestinal tract. As many as one-quarter of patients with IBD initially present in childhood or adolescence. Multiple methods can be used to diagnose IBD in this age group, including computed tomographic (CT) enterography, magnetic resonance (MR) enterography, small bowel follow-through examination, ileocolonoscopy, and capsule endoscopy. However, CT enterography and MR enterography have become the imaging modalities of choice due to their exquisite image quality, rapid acquisition time, lack of need for bowel preparation, and ability to help diagnose the extraintestinal complications of IBD. In addition to being radiation free, MR enterography can help evaluate peristalsis, has high contrast resolution, and allows the use of diffusion weighted imaging. The authors discuss the use of CT enterography and MR enterography in the context of pediatric IBD in terms of advantages and disadvantages, protocol, and imaging findings. PMID- 24224582 TI - Invited commentary. PMID- 24224583 TI - Writing good multiple-choice questions: a brief guide for radiologists. PMID- 24224584 TI - Multidetector CT of emergent biliary pathologic conditions. AB - Various biliary pathologic conditions can lead to acute abdominal pain. Specific diagnosis is not always possible clinically because many biliary diseases have overlapping signs and symptoms. Imaging can help narrow the differential diagnosis and lead to a specific diagnosis. Although ultrasonography (US) is the most useful imaging modality for initial evaluation of the biliary system, multidetector computed tomography (CT) is helpful when US findings are equivocal or when biliary disease is suspected. Diagnostic accuracy can be increased by optimizing the CT protocol and using multiplanar reformations to localize biliary obstruction. CT can be used to diagnose and stage acute cholecystitis, including complications such as emphysematous, gangrenous, and hemorrhagic cholecystitis; gallbladder perforation; gallstone pancreatitis; gallstone ileus; and Mirizzi syndrome. CT also can be used to evaluate acute biliary diseases such as biliary stone disease, benign and malignant biliary obstruction, acute cholangitis, pyogenic hepatic abscess, hemobilia, and biliary necrosis and iatrogenic complications such as biliary leaks and malfunctioning biliary drains and stents. Treatment includes radiologic, endoscopic, or surgical intervention. Familiarity with CT imaging appearances of emergent biliary pathologic conditions is important for prompt diagnosis and appropriate clinical referral and treatment. PMID- 24224585 TI - Secretin-enhanced MR cholangiopancreatography: spectrum of findings. AB - Magnetic resonance cholangiopancreatography (MRCP) is the most effective, safe, noninvasive magnetic resonance (MR) imaging technique for the evaluation of the pancreaticobiliary ductal system. The MRCP imaging technique has substantially improved during the past 2 decades and is based mainly on the acquisition of heavily T2-weighted MR images, with variants of fast spin-echo sequences. MRCP can also be performed by utilizing the hormone secretin, which stimulates a normal pancreas to secrete a significant amount of fluid while transiently increasing the tone of the sphincter of Oddi. The transient increase in the diameter of the pancreatic duct improves the depiction of the ductal anatomy, which can be useful in patients in whom detailed evaluation of the pancreatic duct is most desired because of a suspicion of pancreatic disease. Improved depiction of the ductal anatomy can be important in (a) the differentiation of side-branch intraductal papillary mucinous neoplasms from other cystic neoplasms and (b) the diagnosis and classification of chronic pancreatitis, the disconnected pancreatic duct syndrome, and ductal anomalies such as anomalous pancreaticobiliary junction and pancreas divisum. In patients examined after pancreatectomy, stimulation with secretin can give information about the patency of the pancreaticoenteric anastomosis. Duodenal filling during the secretin enhanced phase of the MRCP examination can be used to estimate the excretory reserve of the pancreas. Secretin is well tolerated, and complications are rarely seen. Secretin-enhanced MRCP is most useful in (a) the evaluation of acute and chronic pancreatitis, congenital variants of the pancreaticoduodenal junction, and intraductal papillary mucinous neoplasms and (b) follow-up of patients after pancreatectomy. PMID- 24224586 TI - Functional imaging for radiation treatment planning, response assessment, and adaptive therapy in head and neck cancer. AB - Patients with squamous cell carcinomas (SCCs) of the head and neck are increasingly treated nonsurgically. Imaging plays a critical role in helping define the targets for radiation therapy, especially intensity-modulated radiation therapy, in which the dose gradients are steep. Anatomic imaging with conventional modalities, particularly computed tomography (CT), has been used in patients with head and neck SCCs, but this approach has limitations. Functional imaging techniques, including positron emission tomography (PET) combined with CT or magnetic resonance (MR) imaging, offer complementary information and can be used noninvasively to assess a range of biomarkers in patients with head and neck SCCs, including hypoxia, cell proliferation and apoptosis, and epidermal growth factor receptor status. These biologic markers can be monitored before, during, and after treatment to improve patient selection for specific therapeutic strategies, guide adaptation of therapy, and potentially facilitate more accurate assessment of disease response. This article discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning and reviews the potential of molecular imaging biomarkers for response assessment and therapy adaptation. The uses of PET tracers for imaging cellular processes such as metabolism, proliferation, hypoxia, and cell membrane synthesis are explored, and applications for MR techniques such as dynamic contrast material-enhanced imaging, diffusion-weighted imaging, blood oxygenation level-dependent imaging, and MR spectroscopy are reviewed. The potential of integrated PET/CT perfusion imaging and hybrid PET/MR imaging also is highlighted. These developments may allow more individualized treatment planning in patients with head and neck SCCs in the emerging era of personalized medicine. PMID- 24224587 TI - Weightless. PMID- 24224588 TI - CT findings of thoracic manifestations of primary Sjogren syndrome: radiologic pathologic correlation. AB - Primary Sjogren syndrome is an immune-mediated exocrinopathy characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands. Various systemic extraglandular disorders are associated with primary Sjogren syndrome, and the thorax is commonly affected. The pulmonary manifestations of primary Sjogren syndrome may be categorized as airway abnormalities, interstitial pneumonias, and lymphoproliferative disorders; in each category, bronchiectasis or centrilobular nodules, nonspecific interstitial pneumonia, and lymphoid interstitial pneumonia are common. These manifestations do not usually occur in isolation; they are concomitantly seen with other types of lesions. Mucosa associated lymphoid tissue (MALT) lymphoma and amyloidosis are key components of lymphoproliferative disorders, and MALT lymphoma should always be considered because its morphologic characteristics are similar to those of benign lymphoproliferative disorders. Amyloidosis is rare but important because it carries a risk for underlying MALT lymphoma or plasmacytoma, and it may lead to hemoptysis during biopsy. In addition, thin-walled air cysts are characteristic of primary Sjogren syndrome, irrespective of the main pulmonary manifestations. Lymphadenopathy and multilocular thymic cysts may be seen in the mediastinum. During the follow-up period, there is a risk for acute exacerbation of interstitial pneumonia and development of malignant lymphoma. Often, primary Sjogren syndrome is subclinical, but there are various underlying risks. Thus, imaging findings are important. In addition to the various types of interstitial pneumonia and airway abnormalities, air cysts and mediastinal manifestations may help diagnose primary Sjogren syndrome. PMID- 24224589 TI - The many faces of injury with organization in the lung. PMID- 24224590 TI - From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia. AB - Organization, characterized by fibroblast proliferation, is a common and nearly universal response to lung injury whether it is focal or diffuse. Despite the vast range of injurious agents, the lung's response to injury is quite limited, with a similar pattern of reaction seen radiologically and histologically regardless of the underlying cause. Although there is a tendency to divide organization into distinct entities, the underlying injury to the alveolar epithelial basement membrane is a uniting factor in these processes. This pattern of lung injury is seen in the organizing phase of diffuse alveolar damage, organizing pneumonia (OP), acute fibrinous and organizing pneumonia, and certain types of fibrotic lung disease. In addition, although organization can heal without significant injury, in some instances it progresses to fibrosis, which can be severe. When fibrosis due to organization is present, other histologic and imaging patterns, such as those seen in nonspecific interstitial pneumonia, can develop, reflecting that fibrosis can be a sequela of organization. This article reviews the histologic and radiologic findings of organization in lung injury due to diffuse alveolar damage, OP, and acute fibrinous and organizing pneumonia and helps radiologists understand that the histologic and radiologic findings depend on the degree of injury and the subsequent healing response. PMID- 24224591 TI - Congenital and hereditary causes of sudden cardiac death in young adults: diagnosis, differential diagnosis, and risk stratification. AB - Sudden cardiac death is defined as death from unexpected circulatory arrest usually a result of cardiac arrhythmia-that occurs within 1 hour of the onset of symptoms. Proper and timely identification of individuals at risk for sudden cardiac death and the diagnosis of its predisposing conditions are vital. A careful history and physical examination, in addition to electrocardiography and cardiac imaging, are essential to identify conditions associated with sudden cardiac death. Among young adults (18-35 years), sudden cardiac death most commonly results from a previously undiagnosed congenital or hereditary condition, such as coronary artery anomalies and inherited cardiomyopathies (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy [ARVC], dilated cardiomyopathy, and noncompaction cardiomyopathy). Overall, the most common causes of sudden cardiac death in young adults are, in descending order of frequency, hypertrophic cardiomyopathy, coronary artery anomalies with an interarterial or intramural course, and ARVC. Often, sudden cardiac death is precipitated by ventricular tachycardia or fibrillation and may be prevented with an implantable cardioverter defibrillator (ICD). Risk stratification to determine the need for an ICD is challenging and involves imaging, particularly echocardiography and cardiac magnetic resonance (MR) imaging. Coronary artery anomalies, a diverse group of congenital disorders with a variable manifestation, may be depicted at coronary computed tomographic angiography or MR angiography. A thorough understanding of clinical risk stratification, imaging features, and complementary diagnostic tools for the evaluation of cardiac disorders that may lead to sudden cardiac death is essential to effectively use imaging to guide diagnosis and therapy. PMID- 24224592 TI - Invited commentary. PMID- 24224593 TI - What radiologists need to know about diagnosis and treatment of inflammatory breast cancer: a multidisciplinary approach. AB - Inflammatory breast cancer (IBC) is a rare breast cancer with a highly virulent course and low 5-year survival rate. Trimodality treatment that includes preoperative chemotherapy, mastectomy, and radiation therapy is the therapeutic mainstay and has been shown to improve prognosis. Proper diagnosis and staging of IBC is critical to treatment planning and requires a multidisciplinary approach that includes imaging. Patients with IBC typically present with rapid onset of breast erythema, edema, and peau d'orange. Both tissue diagnosis of malignancy and clinical findings of inflammatory disease are required to confirm diagnosis of IBC. Imaging is used to identify a biopsy target; direct biopsy; stage IBC; differentiate curable from incurable (stage IV) disease; and help plan chemotherapy, surgical management, and radiation therapy. Comparison of baseline and posttreatment images helps confirm and quantitate disease response. When imaging is used early in the course of therapy to noninvasively predict treatment response, optimal tailored strategies for management of IBC can be implemented. Imaging is vital to diagnosis and treatment planning for patients with IBC, and radiologists are an integral part of the multidisciplinary patient care team. PMID- 24224594 TI - AIRP best cases in radiologic-pathologic correlation: metaplastic squamous cell carcinoma of the breast. PMID- 24224597 TI - Traumatic thoracolumbar spine injuries: what the spine surgeon wants to know. AB - The Thoracolumbar Injury Classification and Severity Score (TLICS) is a scoring and classification system developed by the Spine Trauma Study Group in response to the recognition that previous classification systems have limited prognostic value and generally do not suggest treatment pathways. The TLICS provides a spine injury severity score based on three components: injury morphology, integrity of the posterior ligamentous complex (PLC), and neurologic status of the patient. A numerical score is calculated for each category, with a lower point value assigned to a less severe or less urgent injury and a higher point value assigned to a more severe injury requiring urgent management. The total score helps guide decision making about surgical versus nonsurgical management. The TLICS also emphasizes the importance of magnetic resonance imaging in evaluating PLC injury and acknowledges that the primary driver of surgical intervention is the patient's neurologic status. Knowledge of PLC anatomy and its significance is essential in recognizing unstable injuries. Signs of PLC injury at computed tomography include interspinous distance widening, facet joint widening, spinous process fracture, and vertebral subluxation or dislocation. Familiarity with the TLICS will help radiologists who interpret spine trauma imaging studies to effectively communicate findings to spine trauma surgeons. The complete article is available online . PMID- 24224598 TI - US and MR imaging of the extensor compartment of the ankle. AB - Injuries to the extensor compartment of the ankle are uncommon and often are overlooked or misinterpreted at clinical presentation. Ultrasonography (US) and magnetic resonance (MR) imaging play a critical role in the diagnosis and evaluation of these injuries. US is a dynamic, quick, cost-effective imaging method for assessing ankle extensor compartment injuries as an alternative or adjunct to MR imaging. MR imaging provides multiplanar cross-sectional delineation of regional anatomic structures and also can be used to assess the predisposing cause, estimate the extent of injury, and aid in preoperative planning for requisite surgical repair. The spectrum of pathologic conditions affecting the ankle extensor compartment ranges from tendinosis secondary to degenerative, inflammatory, or depositional disease to traumatic tendon or retinacular rupture and entrapment neuropathy. Major components of the ankle extensor compartment at risk for injury include the anterior tibial, extensor hallucis longus, and extensor digitorum longus tendons; the extensor retinacular mechanism; and the anterior tarsal tunnel. Familiarity with the normal anatomic appearance and pathologic features of the ankle extensor compartment at US and MR imaging as well as potential imaging pitfalls is critical for accurate injury evaluation. PMID- 24224599 TI - Plantar tendons of the foot: MR imaging and US. AB - Tendon disorders along the plantar aspect of the foot may lead to significant symptoms but are often clinically misdiagnosed. Familiarity with the normal anatomy of the plantar tendons and its appearance at magnetic resonance (MR) imaging and ultrasonography (US) is essential for recognizing plantar tendon disorders. At MR imaging, the course of the plantar tendons is optimally visualized with dedicated imaging of the midfoot and forefoot. This imaging should include short-axis images obtained perpendicular to the long axis of the metatarsal shafts, which allows true cross-sectional evaluation of the plantar tendons. Normal plantar tendons appear as low-signal-intensity structures with all MR sequences. At US, accurate evaluation of the tendons requires that the ultrasound beam be perpendicular to the tendon. The normal tendon appears as a compact linear band of echogenic tissue that contains a fine, mixed hypoechoic and hyperechoic internal fibrillar pattern. Tendon injuries can be grouped into six major categories: tendinosis, peritendinosis, tenosynovitis, entrapment, rupture, and instability (subluxation or dislocation) and can be well assessed with both MR imaging and US. The radiologist plays an important role in the diagnosis of plantar tendon disorders, and recognizing their imaging appearances at MR imaging and US is essential. PMID- 24224600 TI - Now you see it, now you don't: visual illusions in radiology. AB - Visual illusions are distortions, alterations, or alternatives in the appearance of reality that result primarily from the sensory and perceptual processing mechanisms of the human visual system. These illusions are common phenomena in radiology, and it is important to understand them because they can create the illusion of disease, leading to incorrect image interpretation. Visual illusions in radiology can be organized according to the point in the visual system at which they emerge. Illusions of sensation, including Mach bands and background effect, are "lower-order" visual phenomena that occur as the eye and brain translate light into neural activity. Illusions of perception, such as ambiguous figures and distortion, occur in "higher-order" brain structures that are responsible for coalescing sensory input into a mental image interpreted by the mind. Illusions of image formation (eg, parallax), as the name implies, result from the way images are generated. Some visual illusions occur with all modalities, whereas others tend to be modality specific. The authors discuss a variety of visual illusions, describing their underlying psychologic and neuroscientific basis and demonstrating their relevance to radiology. A thorough understanding of visual illusions in radiology enhances diagnostic accuracy by minimizing the risk of mistaking illusions for disease. PMID- 24224601 TI - Practice corner: the smart CT suite. PMID- 24224602 TI - Proximal and distal terminology revisited. PMID- 24224603 TI - Easier to swallow: pictorial review of structural findings of the pharynx at barium pharyngography. AB - Barium pharyngography remains an important diagnostic tool in the evaluation of patients with dysphagia. Pharyngography can not only help detect functional abnormalities but also help identify a wide spectrum of structural abnormalities in children and adults. These structural abnormalities may reflect malignant or nonmalignant oropharyngeal, hypopharyngeal, or laryngeal processes that deform or alter normal coated mucosal surfaces. Therefore, an understanding of the normal appearance of the pharynx at contrast material-enhanced imaging is necessary for accurate detection and interpretation of abnormal findings. Congenital malformations are more typically identified in the younger population; inflammatory and infiltrative diseases, trauma, foreign bodies, and laryngeal cysts can be seen in all age groups; and Zenker and Killian-Jamieson diverticula tend to occur in the older population. Squamous cell carcinoma is by far the most common malignant process, with contrast-enhanced imaging findings that depend on tumor location and morphology. Treatments of head and neck cancers include total laryngectomy and radiation therapy, both of which alter normal anatomy. Patients are usually evaluated immediately after laryngectomy to detect complications such as fistulas; later, pharyngography is useful for identifying and characterizing strictures. Deviation from the expected posttreatment appearance, such as irregular narrowing or mucosal nodularity, should prompt direct visualization to evaluate for recurrence. Contrast-enhanced imaging of the pharynx is commonly used in patients who present with dysphagia, and radiologists should be familiar with the barium pharyngographic appearance of the normal pharyngeal anatomy and of some of the processes that alter normal anatomy. PMID- 24224604 TI - Maxillary artery: functional and imaging anatomy for safe and effective transcatheter treatment. AB - The maxillary artery is a terminal branch of the external carotid artery. Although the main maxillary artery trunk and most of its branches course within the extracranial space and supply the organs and muscles of the head and neck, other surrounding soft tissues, and the oral and rhinosinusal cavities, other branches supply the dura mater and cranial nerve and can anastomose to the internal carotid artery (ICA). Various pathologic conditions of the intracranial, head, and neck regions can involve the branches of the maxillary artery. Many of these diseases can be treated with endovascular approaches; however, there is a potential risk of complications in the brain parenchyma and cranial nerves related to the meningoneuronal arterial supply and anastomoses to the ICA. Therefore, familiarity with the functional and imaging anatomy of the maxillary artery is essential. In the past, conventional angiography has been the standard imaging technique for depicting the maxillary artery anatomy and related pathologic findings. However, recent advances in computed tomographic, magnetic resonance, and rotational angiography have further elucidated the maxillary artery anatomy by means of three-dimensional representations. Understanding the functional and imaging anatomy of the maxillary artery allows safe and successful transcatheter treatment of pathologic conditions in the maxillary artery territories. PMID- 24224605 TI - Pierre Perrault, the hydrologic cycle and the scientific revolution. PMID- 24224606 TI - Cloning and expression profiling of odorant-binding proteins in the tarnished plant bug, Lygus lineolaris. AB - In insects, the perception and discrimination of odorants requires the involvement of odorant-binding proteins (OBPs). To gain a better molecular understanding of olfaction in the agronomic pest Lygus lineolaris (the tarnished plant bug), we used a transcriptomics-based approach to identify potential OBPs. In total, 33 putative OBP transcripts, including the previously reported Lygus antennal protein (LAP), were identified based on the characteristic OBP Cys signature and/or sequence similarity with annotated orthologous sequences. The L. lineolaris OBP (LylinOBP) repertoire consists of 20 'classic' OBPs, defined by the spacing of six conserved Cys residues, and 12 'Plus-C' OBPs, defined by the spacing of eight conserved Cys and one conserved Pro residue. Alternative splicing of OBP genes appears to contribute significantly to the multiplicity of LylinOBP sequences. Microarray-based analysis of chemosensory tissues (antennae, legs and proboscis) revealed enrichment of 21 LylinOBP transcripts in antennae, 12 in legs, and 15 in proboscis, suggesting potential roles in olfaction and gustation respectively. PCR-based determination of transcript abundance for a subset of the LylinOBP genes across multiple adult tissues yielded results consistent with the hybridization data. PMID- 24224607 TI - Feasibility evaluation of a stepped procedure to identify community-dwelling frail older people in general practice. A mixed methods study. AB - BACKGROUND: Implementation of frailty identification methods in general practice has hardly been established. To achieve successful implementation, general practitioners (GPs) should be provided with an identification method that suits their needs. EASYcare-TOS is a new frailty identification method that uses a stepped approach and is specifically developed for use in general practice. The first step consists of the GP's frailty judgment based on his prior information on the patient. If the judgment is 'uncertain' or 'frail,' additional data are collected by a primary care nurse (PCN). The frailty decision is based on clinical reasoning by the GP, without applying predefined cut-offs in a numerical score. OBJECTIVE: To evaluate the acceptability of EASYcare-TOS in daily general practice. METHODS: A mixed-methods study was conducted. Questionnaires were sent to all professionals (n = 25) who participated in the EASYcare-TOS validation study. Subsequently, semi-structured interviews with primary care professionals (n = 12) and patients (n = 9) were conducted. RESULTS: Time investment was generally perceived as acceptable. Twenty-two professionals (88%) found a two step model (very) useful in the identification instrument. Seventeen professionals (68%) valued making the final frailty decision by their own clinical reasoning. Patients appreciated the broad assessment and the advice given based on the assessment. According to 24 (96%) professionals, EASYcare-TOS improved the quality of patient care. GPs stated that implementation will ask for reconsidering allocation of tasks in general practices and adequate reimbursement. CONCLUSION: EASYcare-TOS is a new identification method that fits the needs of primary care professionals to a large extent and is acceptable in daily practice. PMID- 24224608 TI - Quality of red blood cells washed using an automated cell processor with and without irradiation. AB - BACKGROUND: Sterile washing of red blood cells (RBCs) and use of an additive solution permits longer postwash storage. The effect of irradiation during this extended storage time is unclear. STUDY DESIGN AND METHODS: RBCs were washed 14 days after collection using an automated cell processor and stored in saline adenine-glucose-mannitol. To determine how long washed and irradiated RBCs could be stored, units were irradiated 1, 4, 5, and 7 days after washing and in vitro quality was assessed. Determined limits of postwash storage time for washed and washed and irradiated RBCs were validated. Quality assessment included percent recovery, hemoglobin (Hb), hemolysis, extracellular K(+) , and adenosine triphosphate. Immunoglobulin (Ig)A levels were measured in the nonirradiated arm. RESULTS: RBCs irradiated 1 and 4 days after washing had unacceptably high hemolysis by Day 7 postwash, not meeting the acceptance criterion (<0.8% hemolysis in 98% of units with 95% confidence). Therefore, a 48-hour maximum storage time after irradiation was chosen. Storage limits tested in the validation phase were as follows: washing on Day 14 and subsequent storage for 7 days (washed RBCs) and washing on Day 14, irradiation on Day 19, and subsequent storage for 48 hours (washed and irradiated RBCs). All units met criteria for Hb, hematocrit, hemolysis, and sterility for washed RBCs. However, RBCs were washed with less than 2 L of saline, and IgA levels in 27 of 40 units were too high to be suitable for transfusion to IgA-deficient recipients. CONCLUSION: The extended expiry for washed and washed and irradiated RBCs met requirements for all indications except transfusion to IgA-deficient recipients. PMID- 24224609 TI - A kinetic isotope effect and isotope exchange study of the nonenzymatic and the equine serum butyrylcholinesterase-catalyzed thioester hydrolysis. AB - Formylthiocholine (FTC) was synthesized and found to be a substrate for nonenzymatic and butyrylcholinesterase (BChE)-catalyzed hydrolysis. Solvent (D2O) and secondary formyl-H kinetic isotope effects (KIEs) were measured by an NMR spectroscopic method. The solvent (D2O) KIEs are (D2O)k = 0.20 in 200 mM HCl, (D2O)k = 0.81 in 50 mM HCl, and (D2O)k = 4.2 in pure water. The formyl-H KIEs are (D)k = 0.80 in 200 mM HCl, (D)k = 0.77 in 50 mM HCl, (D)k = 0.75 in pure water, (D)k = 0.88 in 50 mM NaOH, and (D)(V/K) = 0.89 in the BChE-catalyzed hydrolysis in MES buffer at pH 6.8. Positional isotope exchange experiments showed no detectable exchange of (18)O into the carbonyl oxygen of FTC or the product, formate, under any of the above conditions. Solvent nucleophile-O KIEs were determined to be (18)k = 0.9917 under neutral conditions, (18)k = 1.0290 (water nucleophile) or (18)k = 0.989 (hydroxide nucleophile) under alkaline conditions, and (18)(V/K) = 0.9925 for BChE catalysis. The acidic, neutral, and BChE catalyzed reactions are explained in terms of a stepwise mechanism with tetrahedral intermediates. Evidence for a change to a direct displacement mechanism under alkaline conditions is presented. PMID- 24224611 TI - 2-Pyridonate titanium complexes for chemoselectivity. Accessing intramolecular hydroaminoalkylation over hydroamination. AB - Chemoselectivity of intramolecular hydroaminoalkylation over hydroamination has been achieved with a bis(3-phenyl-2-pyridonate) titanium complex. Primary aminoalkenes are selectively alpha-alkylated by C-H functionalization adjacent to nitrogen to access five- and six-membered cycloalkylamines with a good substrate dependent diastereoselectivity of up to 19:1. PMID- 24224610 TI - Comparison of protein immunoprecipitation-multiple reaction monitoring with ELISA for assay of biomarker candidates in plasma. AB - Quantitative analysis of protein biomarkers in plasma is typically done by ELISA, but this method is limited by the availability of high-quality antibodies. An alternative approach is protein immunoprecipitation combined with multiple reaction monitoring mass spectrometry (IP-MRM). We compared IP-MRM to ELISA for the analysis of six colon cancer biomarker candidates (metalloproteinase inhibitor 1 (TIMP1), cartilage oligomeric matrix protein (COMP), thrombospondin-2 (THBS2), endoglin (ENG), mesothelin (MSLN) and matrix metalloproteinase-9 (MMP9)) in plasma from colon cancer patients and noncancer controls. Proteins were analyzed by multiplex immunoprecipitation from plasma with the ELISA capture antibodies, further purified by SDS-PAGE, digested and analyzed by stable isotope dilution MRM. IP-MRM provided linear responses (r = 0.978-0.995) between 10 and 640 ng/mL for the target proteins spiked into a "mock plasma" matrix consisting of 60 mg/mL bovine serum albumin. Measurement variation (coefficient of variation at the limit of detection) for IP-MRM assays ranged from 2.3 to 19%, which was similar to variation for ELISAs of the same samples. IP-MRM and ELISA measurements for all target proteins except ENG were highly correlated (r = 0.67 0.97). IP-MRM with high-quality capture antibodies thus provides an effective alternative method to ELISA for protein quantitation in biological fluids. PMID- 24224612 TI - Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a Hispanic population. AB - To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05-18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96-13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis. PMID- 24224613 TI - Retrospective assessment of exposure to chemicals for a microelectronics and business machine manufacturing facility. AB - A retrospective exposure assessment was performed for use in a health outcomes study of a facility manufacturing circuit boards, business machines, and other equipment during the years 1969-2002. A matrix was developed identifying chemical use by department-year based on company-provided information. Use of six chemical agents (fiberglass, lead, methylene chloride, methyl chloroform, perchloroethylene, and trichloroethylene) and six chemical classes (acid-base, aromatic hydrocarbons, chlorinated hydrocarbons, other hydrocarbons, chlorofluorocarbons, and metals), and general (including unspecified) chemicals was identified. The matrix also contained an assignment for each department-year categorizing the potential for use of chemicals as negligible, intermittent/incidental, or routine. These department-based exposure matrix data were combined with work history data to provide duration of potential chemical use for workers. Negligible, intermittent/incidental or routine extent-of chemical-use categories comprised 42.6%, 39.4%, and 17.9%, respectively, of total person-years of employment. Cumulative exposure scores were also developed, representing a relative measure of the cumulative extent of potential exposure to the six chemical agents, six chemical classes, and general (including unspecified) chemicals. Additionally, the study period was divided into manufacturing eras showing trends in chemical use, and showing that process use of trichloroethylene and methylene chloride ended in the mid-1980s and the mid 1990s, respectively. This approach may be useful in other assessments addressing a variety of chemicals, and with data constraints common to retrospective chemical exposure studies. PMID- 24224614 TI - Myocardial perfusion defects in patients with chronic hepatitis B infection. AB - BACKGROUND AND AIM: The association between hepatitis B virus (HBV) infection and myocardial injury has yet to be elucidated. We sought to investigate myocardial conditions in patients with chronic HBV infection. METHODS: In 47 consecutive patients with chronic hepatitis B who had no overt heart disease, we performed electrocardiography, echocardiography, serum tests for myocardial injury, and thallium-201 myocardial scintigraphy. Myocardial perfusion defects were confirmed by the severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. The SS was followed before and after interferon (IFN) therapy in 10 patients. RESULTS: Abnormal ECGs were found in 9% of patients with chronic hepatitis B. SS values in the hepatitis group were significantly higher than in the control group (P < 0.0001). Abnormal SS values were found in 47% of the chronic hepatitis B patients. Independent factors related to higher pretreatment SS were serum HBV DNA titer and IgG level. After interferon (IFN) therapy, the SS values of responders were significantly reduced (P <= 0.02); SS values of nonresponders were not significantly different before and after IFN therapy. SS values altered following IFN therapy, along with serum IgG concentrations. CONCLUSIONS: Myocardial perfusion defects were found in 47% of the patients with chronic hepatitis B and improved along with HBV reduction with IFN administration. SS improvement was closely correlated with decreases in serum IgG levels. PMID- 24224616 TI - Study of the structural and the spectral characteristics of [C3N3(NH2)3]n (n = 1 4) clusters. AB - Previous research has shown that interactions between melamine molecules within a cluster can give rise to the molecular self-assembly and that the spectral characteristic of melamine can be used to inspect melamine in a carrier. Although the structural and spectral characteristics of an isolated single melamine molecule and the molecular arrays on metal or semiconductor surfaces have been studied extensively, little is known about that of isolated multimolecular melamine clusters. In this work, density functional theory (DFT) calculations at the omega-B97XD/6-311++G(d,p) level were performed to study the structural and spectral characteristics of isolated melamine clusters [C3N3(NH2)3]n (n = 1-4) in the ground state. The calculation shows that a ground-state single melamine molecule takes a quasi-planar structure. The C and N atoms of the molecule are in one plane, which we call the molecular plane, while the H atoms deviate slightly from the molecular plane. When melamine molecules gather to form a cluster, the intermolecular hydrogen bonds (IHBs) N-H...N will arise, with the lengths of H...N in the range from 1.960 to 1.970 A; the length of N-H will be elongated to 1.022 A from its original of 1.004 A, the N-H...N bond angles will be about 176 degrees , and the average single-bond binding energy will be approximately -0.285 eV. In a multimolecular cluster, each melamine molecule still takes the quasi planar structure. Each molecular plane in the cluster retains a planar structure, and some H atoms diverge more from their molecular planes. The molecular planes in a cluster are not coplanar, and the dihedral angle between the molecular planes of two neighboring melamine molecules ranges from 38 to 40 degrees . In addition, the theoretical study of the infrared (IR) spectrum and nuclear magnetic resonance (NMR) spectrum of [C3N3(NH2)3]n (n = 1-4) was conducted. The results confirm the existence of IHBs in a multimolecular melamine cluster and reveal the symmetry of the electron cloud distribution in the melamine clusters. Experimental study of the IR for solid-state melamine and (13)C NMR spectra for both solid- and liquid-state melamine samples were also carried out, in which the corresponding spectral characteristics of [C3N3(NH2)3]n (n = 2-4) clusters deduced from theoretical study were observed. Findings of this study may serve as theoretical references for future identification and utilization of melamine clusters. PMID- 24224615 TI - Identification of blood meal sources in Aedes vexans and Culex quinquefasciatus in Bernalillo County, New Mexico. AB - Culex quinquefasciatus Say (Diptera: Culicidae) and Aedes vexans Meigen are two of the most abundant mosquitoes in Bernalillo County, New Mexico, USA. In this study, a polymerase chain reaction based methodology was used to identify the sources of blood meals taken by these two species. Ae. vexans was found to take a large proportion of its meals from mammals. Although less specific in terms of its blood meal preferences, Cx. quinquefasciatus was found to feed more commonly on birds. The results for Ae. vexans are similar to those reported for this species in other parts of their geographic range. Cx. quinquefasciatus appears to be more variable in terms of its host feeding under different environmental or seasonal circumstances. The implications of these results for arbovirus transmission are discussed. PMID- 24224617 TI - Urine alkalization improves the problems of pain and sleep in hypersensitive bladder syndrome. AB - OBJECTIVE: To investigate the efficacy of urine alkalization therapy using citrates in patients with hypersensitive bladder syndrome. METHODS: A total of 76 patients with urinary frequency were assessed for their symptoms using a 2-day voiding diary as well as the urine pH at each voiding during the screening period. Their symptoms were also assessed by pain score, King's health questionnaire, and O'Leary-Sant symptom and problem index scores. Finally, 50 patients were evaluated for changes in symptoms after oral treatment with citrates for 2-4 weeks after the screening period. RESULTS: After the treatment, significant increases in the urine pH (from 5.8 +/- 0.4 to 6.3 +/- 0.4; increment of 0.5 +/- 0.4; P < 0.01), and significant decreases in the number of micturitions per day (from 14.5 +/- 6.5 to 13.5 +/- 5.9; P = 0.02) and the number of episodes of pain/discomfort per day (from 7.8 +/- 6.8 to 6.1 +/- 7.1; P = 0.02) were observed. In the King's health questionnaire, the sleep/energy domain score was significantly improved (from 60.0 +/- 25.0 to 50.3 +/- 29.6; P < 0.01). In a subgroup analysis based on urine pH (urine pH <6.2 and >=6.2), significant improvements in the voiding symptoms, the sleep/energy domain score and the O'Leary-Sant problem index were observed in the group with urine pH of >=6.2. There were statistically significant differences between the subgroups in the volume per voiding, maximum volume per voiding and the problem index. In addition, the subgroup, in which patients had pain in the screening period, showed statistically significant improvements in the number of micturitions per day, episodes of pain/discomfort per day, the sleep/energy domain score and the problem index. CONCLUSIONS: Urine alkalization therapy is likely to be effective in the treatment for hypersensitive bladder syndrome. PMID- 24224618 TI - Structure and function correlation in a patient with dengue-associated maculopathy. PMID- 24224619 TI - Acapsular clinical Staphylococcus aureus isolates lack agr function. AB - Staphylococcus aureus is a major human pathogen causing community- and hospital acquired infections. Capsule production of S. aureus confers protection against host defence. There is a lack of information concerning the association of capsular polysaccharide (CP) expression and activity of the accessory gene regulator (agr) in clinical S. aureus isolates. Production of CP and agr expression were assessed in 195 S. aureus isolates from infected patients at a German University Hospital. Northern blot analysis revealed that S. aureus strains with a non-functional agr locus were more likely to be CP-negative than strains with a functional agr locus. PMID- 24224620 TI - The National Children's Study--a proposed plan. AB - With its coordinated longitudinal biologic, environmental-exposure, and phenotypic data and samples, the National Children's Study is aiming to provide an important resource for understanding children's growth, development, and health. PMID- 24224621 TI - Expediting drug development--the FDA's new "breakthrough therapy" designation. AB - The FDA's new "breakthrough therapy" designation for investigational drugs adds to the agency's portfolio of expedited programs for serious conditions. The designation requires preliminary clinical evidence demonstrating substantial improvement over existing therapies. PMID- 24224622 TI - Voided midstream urine culture and acute cystitis in premenopausal women. AB - BACKGROUND: The cause of acute uncomplicated cystitis is determined on the basis of cultures of voided midstream urine, but few data guide the interpretation of such results, especially when gram-positive bacteria grow. METHODS: Women from 18 to 49 years of age with symptoms of cystitis provided specimens of midstream urine, after which we collected urine by means of a urethral catheter for culture (catheter urine). We compared microbial species and colony counts in the paired specimens. The primary outcome was a comparison of positive predictive values and negative predictive values of organisms grown in midstream urine, with the presence or absence of the organism in catheter urine used as the reference. RESULTS: The analysis of 236 episodes of cystitis in 226 women yielded 202 paired specimens of midstream urine and catheter urine that could be evaluated. Cultures were positive for uropathogens in 142 catheter specimens (70%), 4 of which had more than one uropathogen, and in 157 midstream specimens (78%). The presence of Escherichia coli in midstream urine was highly predictive of bladder bacteriuria even at very low counts, with a positive predictive value of 10(2) colony-forming units (CFU) per milliliter of 93% (Spearman's r=0.944). In contrast, in midstream urine, enterococci (in 10% of cultures) and group B streptococci (in 12% of cultures) were not predictive of bladder bacteriuria at any colony count (Spearman's r=0.322 for enterococci and 0.272 for group B streptococci). Among 41 episodes in which enterococcus, group B streptococci, or both were found in midstream urine, E. coli grew from catheter urine cultures in 61%. CONCLUSIONS: Cultures of voided midstream urine in healthy premenopausal women with acute uncomplicated cystitis accurately showed evidence of bladder E. coli but not of enterococci or group B streptococci, which are often isolated with E. coli but appear to rarely cause cystitis by themselves. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.). PMID- 24224623 TI - A novel prion disease associated with diarrhea and autonomic neuropathy. AB - BACKGROUND: Human prion diseases, although variable in clinicopathological phenotype, generally present as neurologic or neuropsychiatric conditions associated with rapid multifocal central nervous system degeneration that is usually dominated by dementia and cerebellar ataxia. Approximately 15% of cases of recognized prion disease are inherited and associated with coding mutations in the gene encoding prion protein (PRNP). The availability of genetic diagnosis has led to a progressive broadening of the recognized spectrum of disease. METHODS: We used longitudinal clinical assessments over a period of 20 years at one hospital combined with genealogical, neuropsychological, neurophysiological, neuroimaging, pathological, molecular genetic, and biochemical studies, as well as studies of animal transmission, to characterize a novel prion disease in a large British kindred. We studied 6 of 11 affected family members in detail, along with autopsy or biopsy samples obtained from 5 family members. RESULTS: We identified a PRNP Y163X truncation mutation and describe a distinct and consistent phenotype of chronic diarrhea with autonomic failure and a length dependent axonal, predominantly sensory, peripheral polyneuropathy with an onset in early adulthood. Cognitive decline and seizures occurred when the patients were in their 40s or 50s. The deposition of prion protein amyloid was seen throughout peripheral organs, including the bowel and peripheral nerves. Neuropathological examination during end-stage disease showed the deposition of prion protein in the form of frequent cortical amyloid plaques, cerebral amyloid angiopathy, and tauopathy. A unique pattern of abnormal prion protein fragments was seen in brain tissue. Transmission studies in laboratory mice were negative. CONCLUSIONS: Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy. (Funded by the U.K. Medical Research Council and others.). PMID- 24224625 TI - Publication of trials funded by the National Heart, Lung, and Blood Institute. AB - BACKGROUND: Rapid publication of clinical trials is essential in order for the findings to yield maximal benefits for public health and scientific progress. Factors affecting the speed of publication of the main results of government funded trials have not been well characterized. METHODS: We analyzed 244 extramural randomized clinical trials of cardiovascular interventions that were supported by the National Heart, Lung, and Blood Institute (NHLBI). We selected trials for which data collection had been completed between January 1, 2000, and December 31, 2011. Our primary outcome measure was the time between completion of the trial and publication of the main results in a peer-reviewed journal. RESULTS: As of March 31, 2012, the main results of 156 trials (64%) had been published (Kaplan-Meier median time to publication, 25 months, with 57% published within 30 months). Trials that focused on clinical events were published more rapidly than those that focused on surrogate measures (median, 9 months vs. 31 months; P<0.001). The only independent predictors of more rapid publication were a focus on clinical events rather than surrogate end points (adjusted publication rate ratio, 2.11; 95% confidence interval, 1.26 to 3.53; P=0.004) and higher costs of conducting the trial, up to a threshold of approximately $5 million (P<0.001). The 37 trials that focused on clinical events and cost at least $5 million accounted for 67% of the funds spent on clinical trials but received 82% of the citations. After adjustment of the analysis for a focus on clinical events and for cost, trial results that were classified as positive were published more quickly than those classified as negative. CONCLUSIONS: Results of less than two thirds of NHLBI-funded randomized clinical trials of cardiovascular interventions were published within 30 months after completion of the trial. Trials that focused on clinical events were published more quickly than those that focused on surrogate end points. (Funded by the National Heart, Lung, and Blood Institute.). PMID- 24224624 TI - Low-intensity therapy in adults with Burkitt's lymphoma. AB - BACKGROUND: Burkitt's lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children. METHODS: We studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt's lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group). RESULTS: A total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin-etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt's lymphoma. CONCLUSIONS: In this uncontrolled prospective study, low intensity EPOCH-R-based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt's lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov numbers, NCT00001337 and NCT00006436.). PMID- 24224626 TI - Clinical practice: Adult attention deficit-hyperactivity disorder. AB - Short-term trials involving adults with ADHD have shown significant improvements in symptoms with stimulants and atomoxetine; however, data on long-term benefits and risks of these medications, particularly among older persons, have been insufficient. PMID- 24224627 TI - Images in clinical medicine: Unusual bursal fluid. AB - A 73-year-old man with seropositive rheumatoid arthritis and extraarticular involvement (rheumatoid nodules on the right elbow) presented with persistent, painless swelling of the left elbow. His medical history was unremarkable except for hypertension. PMID- 24224628 TI - Case of the Massachusetts General Hospital: Case 35-2013: a 77-year-old man with confusion and malaise. AB - A 77-year-old man was admitted to this hospital because of confusion and malaise after resection of a papillary urothelial cancer. He reported abdominal pain, facial and jaw pain, anorexia, lethargy, weakness, and night sweats; imaging revealed generalized lymphadenopathy. PMID- 24224629 TI - Uncomplicated cystitis--not so simple. PMID- 24224630 TI - When it comes to trials, do we get what we pay for? PMID- 24224631 TI - Asthma and coagulation. PMID- 24224632 TI - Survival in the prostate cancer prevention trial. PMID- 24224633 TI - Survival in the prostate cancer prevention trial. PMID- 24224634 TI - Survival in the prostate cancer prevention trial. PMID- 24224635 TI - Pazopanib versus sunitinib in renal cancer. PMID- 24224636 TI - Pazopanib versus sunitinib in renal cancer. PMID- 24224637 TI - Pazopanib versus sunitinib in renal cancer. PMID- 24224638 TI - Pazopanib versus sunitinib in renal cancer. PMID- 24224639 TI - Videos in clinical medicine: Laryngeal mask airway in medical emergencies. AB - This video demonstrates the placement of a laryngeal mask airway, an alternative airway device that is both efficacious and easy to place. The laryngeal mask airway is routinely used for patients receiving general anesthesia and, increasingly, in patient resuscitation. PMID- 24224640 TI - Images in clinical medicine: Giant C-v waves of tricuspid regurgitation. AB - A 33-year-old woman who had received a diagnosis of tricuspid valve endocarditis caused by MRSA was evaluated for replacement of the tricuspid valve. Videos show giant systolic pulsations during jugular venous examination and severe tricuspid regurgitation during transthoracic ECG. PMID- 24224641 TI - Human papilloma virus is not prevalent in nevus sebaceus. AB - Nevus sebaceus (NS) is a common congenital cutaneous hamartoma that typically presents on the scalp and face at birth or in early childhood. Occasionally NS can be associated with the Schimmelpenning-Feuerstein-Mims syndrome, which presents with concomitant severe neurologic, skeletal, cardiovascular, ophthalmic, and genitourologic disorders. In a previous study, maternal transmission of the human papillomavirus (HPV) and infection of ectodermal stem cells by HPV was postulated to result in the development of NS. In this study we aimed to determine the incidence of HPV infection in pediatric NS samples to further clarify the potential link between HPV and the pathogenesis of NS. NS tissue samples (N = 16) were analyzed for HPV DNA using type-specific, real-time polymerase chain reaction (PCR) targeting HPV 6, 11, 16, and 18 and conventional PCR with modified general primers designed for broad-range HPV detection. The tissues were also histologically evaluated for evidence of HPV infection. HPV DNA was not detected in any of the NS tissue samples using PCR and HPV-associated histopathologic changes were absent in all 16 NS tissues. HPV infection is an unlikely etiologic cause of NS. PMID- 24224642 TI - The gendered impact of Irritable Bowel Syndrome: a qualitative study of patients' experiences. AB - AIM: The aim of the study was to explore the impact of irritable bowel syndrome on daily life from a gender perspective. BACKGROUND: Irritable bowel syndrome is a common functional disorder, characterized by abdominal pain, diarrhoea and/or constipation. Sufferers experience negative emotions due to unpredictable symptoms and sometimes feel trivialized by healthcare professionals. The sufferers' experience of living with this disorder has never been explored from a gender perspective. DESIGN: A qualitative, interpretative method was used. METHODS: A qualitative, hermeneutic method was applied. Interviews were conducted with 19 patients in 2011 and analysed in a constructionist gender framework. Constructionist gender theory views gender and identity as cultural constructs that develop through interplay between the individual and his/her social context and cultural norms. FINDINGS: The main theme to emerge from the interviews was as follows: 'A normative framework of femaleness and maleness leads to suffering for persons with irritable bowel syndrome'. This consists of three interwoven themes: 'Being forced to abandon gender illusions'; 'Being forced to transcend taboos' and 'Reinforced suffering in healthcare encounters'. Men demonstrated masculinity by stressing the importance of being solid family providers while women spoke of nurturing and relational responsibilities in line with traditional notions of femininity. CONCLUSION: The experience of living with irritable bowel syndrome differs between men and women due to differing societal expectations, life situation and the everyday construction of gender identities. Gender stereotyping by healthcare professionals perpetuates rather than alleviates the suffering experienced by men and women with irritable bowel syndrome. In healthcare encounters, women risk being trivialized and men risk being overlooked due to the 'female health concern' label attached to irritable bowel syndrome. PMID- 24224643 TI - Intracellular delivery of universal proteins using a lysine headgroup containing cationic liposomes: deciphering the uptake mechanism. AB - An amino acid-based cationic lipid having a TFA counterion (trifluoroacetic acid counterion) in the lysine headgroup was used to deliver functional proteins into human cervical cancer cells, HeLa, in the presence of serum. Proteins used in the study were fluorescein isothiocyanate (FITC) labeled bovine serum albumin, mouse anti-F actin antibody [NH3], and goat anti mouse IgG conjugated with FITC. The formation of liposome/protein complexes was confirmed using native polyacrylamide gel electrophoresis. Furthermore, the complexes were characterized in terms of their size and zeta potential at different pH values and found to be responsive to changes in pH. The highest delivery efficiency of the liposome/albumin complexes was 99% at 37 degrees C. The liposomes effectively delivered albumin and antibodies as confirmed by confocal laser scanning microscopy (CLSM). Inhibition studies showed that the cellular uptake mechanism of the complexes was via caveolae-mediated endocytosis, and the proteins were subsequently released from either the early endosomes or the caveosomes as suggested by CLSM. Thus, lysine-based cationic liposomes can be a useful tool for intracellular protein delivery. PMID- 24224644 TI - Ontogeny of CYP3A and P-glycoprotein in the liver and the small intestine of the Gottingen minipig: an immunohistochemical evaluation. AB - Despite the increasing use of the minipig as a non-rodent species in general and juvenile toxicity studies, knowledge on their biotransformation processes and their ontogeny is scarce. Such data are prerequisite for the correct interpretation of non-clinical studies in this species. Therefore, the aim of our investigation was to immunohistochemically document the presence of the drug transporter P-glycoprotein (Pgp) and the metabolizing cytochrome P450 (CYP) 3A subfamily in the livers (n = 115) and the small intestines (n = 74) of foetal, neonatal, juvenile and adult Gottingen minipigs. Pgp was expressed in the liver in all age groups, whereas its presence in the jejunum was detected from 86 days of gestation onwards. Low expression of CYP3A was detected in the jejunums and livers from foetal and neonatal piglets. During postnatal development, the immunoreactivity for CYP3A increased in both organs. A centrilobular pattern, with a more intense staining for CYP3A of the hepatocytes surrounding the central vein, was noticed in the postnatal livers. In conclusion, the presented data suggest that the intestinal and hepatic ontogeny of P-glycoprotein and CYP3A in minipigs corresponds to that in man, in which a similar spatio-temporal expression has been reported. PMID- 24224645 TI - Expression of insulin/insulin-like signalling and TOR pathway genes in honey bee caste determination. AB - The development of queen and worker castes in honey bees is induced by differential nutrition, with future queens and workers receiving diets that are qualitatively and quantitatively different. We monitored the gene expression of 14 genes for components of the insulin/insulin-like signalling and TOR pathways in honey bee larvae from 40-88 h after hatching. We compared normally fed queen and normally fed worker larvae and found that three genes showed expression differences in 40-h-old larvae. Genes that show such early differences in expression may be part of the mechanism that transduces nutrition level into a hormone signal. We then compared changes in expression after shifts in diet with those in normally developing queens and workers. Following a shift to the worker diet, the expression of 9/14 genes was upregulated in comparison with queens. Following a shift to the queen diet, expression of only one gene changed. The honey bee responses may function together as a homeostatic mechanism buffering larvae from caste-disrupting variation in nutrition. The different responses would be part of the canalization of both the queen and worker developmental pathways, and as such, a signature of advanced sociality. PMID- 24224646 TI - Fast hydrazone reactants: electronic and acid/base effects strongly influence rate at biological pH. AB - Kinetics studies with structurally varied aldehydes and ketones in aqueous buffer at pH 7.4 reveal that carbonyl compounds with neighboring acid/base groups form hydrazones at accelerated rates. Similarly, tests of a hydrazine with a neighboring carboxylic acid group show that it also reacts at an accelerated rate. Rate constants for the fastest carbonyl/hydrazine combinations are 2-20 M( 1) s(-1), which is faster than recent strain-promoted cycloaddition reactions. PMID- 24224647 TI - The effects of rejuvenation during hypothermic storage on red blood cell membrane remodeling. AB - BACKGROUND: Our previous studies showed that hypothermic storage (HS) induces red blood cell (RBC) microparticle (RMP) generation and changes in phosphatidylserine (PS) and CD47 expression on RBCs and RMPs. The aim of this study was to evaluate the effect of cold rejuvenation treatment at multiple time points during storage on these prehemolytic indicators of RBC membrane storage lesion. STUDY DESIGN AND METHODS: Leukoreduced RBC units in saline-adenine-glucose-mannitol were used to generate three groups: untreated controls, sham-treated units, and units treated with a cold (1-6 degrees C) rejuvenation solution on Day 28, 35, or 42 of HS. Units were assessed for hemolysis, adenosine triphosphate (ATP) concentration, lipid composition, and RMP generation, as well as PS and CD47 expression throughout 49 days of HS. RESULTS: Rejuvenation treatment led to a significant increase in ATP concentration in all units, irrespective of treatment day. There were no significant differences between sham- and rejuvenation-treated RBC samples in the levels of PS externalization, CD47 expression, or the rate of RMP formation. RBCs rejuvenated on Day 28 were enriched in glycerophosphocholine (+23.5%), depleted in sphingomyelin (-14%), and slightly depleted in cholesterol (-3.5%). CONCLUSION: Cold rejuvenation in hypothermically stored RBCs affects the lipid composition of RBCs and respective RMPs in a time-dependent fashion. PMID- 24224648 TI - Does prostate HistoScanningTM play a role in detecting prostate cancer in routine clinical practice? Results from three independent studies. AB - OBJECTIVES: To evaluate the ability of prostate HistoScanningTM (PHS; Advanced Medical Diagnostics, Waterloo, Belgium) to detect, characterize and locally stage prostate cancer, by comparing it with transrectal ultrasonography (TRUS)-guided prostate biopsies, transperineal template prostate biopsies (TTBs) and whole mount radical prostatectomy specimens. SUBJECTS AND METHODS: Study 1. We recruited 24 patients awaiting standard 12-core TRUS-guided biopsies of the prostate to undergo PHS immediately beforehand. We compared PHS with the TRUS guided biopsy results in terms of their ability to detect cancer within the whole prostate and to localize it to the correct side and to the correct region of the prostate. Lesions that were suspicious on PHS were biopsied separately. Study 2. We recruited 57 patients awaiting TTB to have PHS beforehand. We compared PHS with the TTB pathology results in terms of their ability to detect prostate cancer within the whole gland and to localize it to the correct side and to the correct sextant of the prostate. Study 3. We recruited 24 patients awaiting radical prostatectomy for localized prostate cancer to undergo preoperative PHS. We compared PHS with standardized pathological analysis of the whole-mount prostatectomy specimens in terms of their measurement of total tumour volume within the prostate, tumour volume within prostate sextants and volume of index lesions identified by PHS. RESULTS: The PHS-targeted biopsies had an overall cancer detection rate of 38.1%, compared with 62.5% with standard TRUS-guided biopsies. The sensitivity and specificity of PHS for localizing tumour to the correct prostate sextant, compared with standard TRUS-guided biopsies, were 100 and 5.9%, respectively. The PHS-targeted biopsies had an overall cancer detection rate of 13.4% compared with 54.4% for standard TTB. PHS had a sensitivity and specificity for cancer detection in the posterior gland of 100 and 13%, respectively, and for the anterior gland, 6 and 82%, respectively. We found no correlation between total tumour volume estimates from PHS and radical prostatectomy pathology (Pearson correlation coefficient -0.096). Sensitivity and specificity of PHS for detecting tumour foci >=0.2 mL in volume were 63 and 53%. CONCLUSIONS: These three independent studies in 105 patients suggest that PHS does not reliably identify and characterize prostate cancer in the routine clinical setting. PMID- 24224649 TI - A phase 2 study of HQK-1001, an oral fetal haemoglobin inducer, in beta thalassaemia intermedia. PMID- 24224651 TI - Multiple illness perceptions in older adults: effects on physical functioning and medication adherence. AB - OBJECTIVE: Previous research on illness perceptions has focused on single illnesses, but most adults over 65 suffer from multiple illnesses (multimorbidity). This study tests three competing operationalisations of multiple illness perceptions in predicting physical functioning and adherence: (1) main effects and interactions model; (2) peak model with effects of the most prominent illness perception; and (3) combined model with averaged illness perceptions over multiple illnesses. DESIGN: Longitudinal study in N = 215 individuals (65-86 years) with multimorbidity at two measurement points over six months. Participants filled in two Brief Illness Perception Questionnaires (B IPQ) on their two most severe illnesses. MAIN OUTCOME MEASURES: Physical functioning, medication adherence. RESULTS: Factor analyses suggest that the B IPQ contains three dimensions; consequences, control and timeline. Multiple regression models fit the data best for (1) and (3). Timeline (beta = -.18) and control (beta = .21) predict adherence in (1); consequences (beta = .16) and control (beta = .20) in (3). Physical functioning was significantly predicted by interacting control beliefs in (1; beta = .13), by peak consequences in (2; beta = -.14) and by consequences (beta = -.15) in (3). CONCLUSIONS: Individuals with multimorbidity hold both distinct and combined perceptions about their illnesses. To understand individual responses to multimorbidity, perceptions about all illnesses and multimorbidity as entity should be examined. PMID- 24224650 TI - HIV-1 nucleocapsid proteins as molecular chaperones for tetramolecular antiparallel G-quadruplex formation. AB - HIV-1 nucleocapsid proteins (NCps) facilitate remodeling of nucleic acids to fold thermodynamically stable conformations, and thus called nucleic acid chaperones. To date only little is known on the stoichiometry, NCp-NCp interactions, chaperone activity on G-quadruplex formation, and so on. We report here the direct and real-time analysis on such properties of proteolytic intermediate NCp15 and mature NCp7 using DNA origami. The protein particles were found to predominantly exist in monomeric form, while dimeric and multimeric forms were also observed both in free solution and bound to the quadruplex structure. The formation and the dissociation events of the G-quadruplexes were well documented in real-time and the intermediate-like states were also visualized. We anticipate that this pioneering study will strengthen our understanding on the chaperone activity of HIV-1 proteins which in turn will be helpful for the drug design based on G-quadruplex and also for the development of drugs against AIDS. PMID- 24224653 TI - Selling anti-aging research: the perils of mixed messages. PMID- 24224652 TI - Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. AB - Interleukin-12 (IL-12) p70 and IL-23 are bioactive cytokines and their biological functions are becoming clear. Increased expression of IL-7 in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis. Here, we describe the induction of IL-7 in primary mouse and human microglia, BV-2 microglial cells, mouse peritoneal macrophages and astrocytes by IL-12p70. Interestingly, IL-12 strongly induced the expression of IL-7 whereas IL-23 and other p40 family members remained weak inducers of IL-7 in these cell types. Consistently, IL-12, but not IL-23 and other p40 family members, induced IL-7 promoter-driven luciferase activity in microglial cells. Among various stimuli tested, IL-12 emerged as the most potent stimulus followed by bacterial lipopolysaccharide and HIV-1 gp120 in inducing the activation of IL-7 promoter in microglial cells. Furthermore, increase in IL-7 mRNA expression by over-expression of IL-12p35 subunit, but not p40 and IL-23 p19 subunit, confirm that p35, but not p40 and p19, is responsible for the induction of IL-7. Finally, by using primary microglia from IL-12 receptor beta1-deficient (IL-12Rbeta1(-/-)) and IL-12Rbeta2( /-) mice, we demonstrate that IL-12 induces the expression of IL-7 in microglia and macrophages via both IL-12Rbeta2 and IL-12Rbeta1. These studies delineate a novel biological function of IL-12 that is absent in IL-23 and other p40 family members. PMID- 24224654 TI - Identification of potent and selective cathepsin S inhibitors containing different central cyclic scaffolds. AB - Starting from the weakly active dual CatS/K inhibitor 5, structure-based design supported by X-ray analysis led to the discovery of the potent and selective (>50,000-fold vs CatK) cyclopentane derivative 22 by exploiting specific ligand receptor interactions in the S2 pocket of CatS. Changing the central cyclopentane scaffold to the analogous pyrrolidine derivative 57 decreased the enzyme as well as the cell-based activity significantly by 24- and 69-fold, respectively. The most promising scaffold identified was the readily accessible proline derivative (e.g., 79). This compound, with an appealing ligand efficiency (LE) of 0.47, included additional structural modifications binding in the S1 and S3 pockets of CatS, leading to favorable in vitro and in vivo properties. Compound 79 reduced IL-2 production in a transgenic DO10.11 mouse model of antigen presentation in a dose-dependent manner with an ED50 of 5 mg/kg. PMID- 24224655 TI - A novel urinary metabolite signature for diagnosing major depressive disorder. AB - Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS DA analysis of data from training samples (82 first-episode, drug-naive MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD. PMID- 24224656 TI - Dexamethasone in outcome of patients with hepatitis B virus-related acute-on chronic liver failure. AB - BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV) is a severe disease with high mortality. Immune injury plays an important role during the early stage of the disease. Our research aimed to investigate the safety and efficacy of dexamethasone therapy for patients with HBV-related ACLF. METHODS: A total of 134 inpatients with HBV-induced ACLF were enrolled from January 2009 to December 2012. All the patients received the standard medicine treatment (SMT), among whom 31 cases underwent additional dexamethasone injection for three times (dexamethasone treatment [DMT] Group). A total of 35 patients (SMT Group) matched for baseline characters served as controls. Both the groups were followed up for 12 weeks. The survival rates, liver functions, and complications were recorded. RESULTS: The 12-week cumulative survival rates were 45.7% (16/35)and 48.4% (15/31) for SMT Group and DMT Group, respectively, and no significant differences were found (P = 0.959). There were no dramatic differences in liver function and model for end-stage liver disease (MELD) score at 1, 2, 4, 8, and 12 weeks between two groups. There were no significant differences in the incidence of complications (i.e. infection, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome, and ascites) from 1 to 12 weeks between Group SMT and Group DMT. More than 40 ages, MELD score more than 28 and encephalopathy were independent risk factors for the mortality of patients. CONCLUSIONS: Dexamethasone cannot improve liver functions and 12 week survival rates of patients with HBV-related ACLF. Age, MELD score, and encephalopathy are independent risk factors. PMID- 24224657 TI - Site-selective displacement of tobramycin hydroxyls for preparation of antimicrobial cationic amphiphiles. AB - A short site-selective strategy for the activation and derivatization of alcohols of the clinically important aminoglycoside tobramycin is reported. The choice of amine protecting group affected the site-selective conversion of secondary alcohols of tobramycin into leaving groups. Temperature-dependent, chemoselective sequential nucleophilic displacements resulted in hetero- and homodithioether tobramycin-based cationic amphiphiles that demonstrated marked antimicrobial activity and impressive membrane selectivity. PMID- 24224658 TI - The scholarship of intellectual generosity. PMID- 24224659 TI - In situ real time infrared spectroscopy of sorption of (poly)molybdate ions into layered double hydroxides. AB - The sorption of (poly)molybdate ions into layered double hydroxides (LDHs), with Zn(2+) and Al(3+) cations, has been followed by in situ infrared spectroscopy using the attenuated total reflection technique. The exchange between solution molybdate species and interlayer anions has been followed in real time, illustrating the different behavior of molybdate ions and polymolybdate species. In a first part, the Mo(VI) speciation in solution was performed by comparison of thermodynamical calculations and infrared spectroscopy of solutions with different pH. Decomposition of bands between 800 to 1000 cm(-1), corresponding to the (Mo-O) stretching vibration, has permitted to identify major (poly)molybdate species. In the presence of LDH, the measurements have shown a high affinity for heptamolybdate (Mo7O24(6-)) species, and its preferential sorption in comparison with molybdate ions or other protonated polymolybdate species even if it represents very small fractions. From these measurements, the affinity series Mo7O24(6-) > CO3(2-) > MoO4(2-) > SO4(2-) have been directly obtained. PMID- 24224660 TI - Editorial Comment to Localized non-conventional renal cell carcinoma: prediction of clinical outcome according to histology. PMID- 24224661 TI - Recombinant receptor-binding domain of diphtheria toxin increases the potency of curcumin by enhancing cellular uptake. AB - Diphtheria toxin (DT) binds to a specific cell surface receptor, gets internalized, and causes cytotoxicity through its catalytic domain. The toxicity of DT is used in several therapeutic molecules. Here, we have exploited the receptor-binding ability of DT to increase cellular uptake of curcumin, a hydrophobic molecule with low bioavailability and cellular uptake. We have expressed only the receptor-binding domain of DT (RDT) in Escherichia coli. Purified RDT binds to the receptor with an affinity equivalent to that of full length DT. It also binds to curcumin forming a curcumin-RDT complex, and this increases the fluorescence intensity and fluorescence lifetime of curcumin. The curcumin-RDT complex binds to the receptor and associates with human glioblastoma cells (U-87 MG) expressing the receptor. The cellular uptake of curcumin is higher for the curcumin-RDT complex than curcumin alone. This increase in uptake enhances the antiproliferative effect of curcumin and induces apoptosis of these cells even at a lower dose. PMID- 24224662 TI - Guidelines for the collaborative care of glaucoma patients and suspects by ophthalmologists and optometrists in Australia. PMID- 24224663 TI - What counts as effective communication in nursing? Evidence from nurse educators' and clinicians' feedback on nurse interactions with simulated patients. AB - AIM: To examine the feedback given by nurse educators and clinicians on the quality of communication skills of nurses in interactions with simulated patients. BACKGROUND: The quality of communication in interactions between nurses and patients has a major influence on patient outcomes. To support the development of effective nursing communication in clinical practice, a good understanding of what constitutes effective communication is helpful. DESIGN: An exploratory design was used involving individual interviews, focus groups and written notes from participants and field notes from researchers to investigate perspectives on nurse-patient communication. METHODS: Focus groups and individual interviews were held between August 2010-September 2011 with a purposive sample of 15 nurse educators and clinicians who observed videos of interactions between nurses and simulated patients. These participants were asked to give oral feedback on the quality and content of these interactions. Verbatim transcriptions were undertaken of all data collected. All written notes and field notes were also transcribed. Thematic analysis of the data was undertaken. FINDINGS: Four major themes related to nurse-patient communication were derived from the educators' and clinicians' feedback: approach to patients and patient care, manner towards patients, techniques used for interacting with patients and generic aspects of communication. CONCLUSION: This study has added to previous research by contributing grounded evidence from a group of nurse educators and clinicians on the aspects of communication that are relevant for effective nurse patient interactions in clinical practice. PMID- 24224664 TI - Incongruence between multi-locus sequence analysis (MLSA) and whole-genome-based phylogenies: Pseudomonas syringae pathovar pisi as a cautionary tale. AB - Previous phylogenies, built using a subset of genomic loci, split Pseudomonas syringae pv. pisi into two well-supported clades and implied convergence in host range for these lineages. The analysis of phenotypic and genotypic data within the context of this phylogenetic relationship implied further convergence at the level of virulence gene loss and acquisition. We generate draft genome assemblies for two additional P. syringae strains, isolated from diseased pea plants, and demonstrate incongruence between phylogenies created from a subset of the data compared with the whole genomes. Our whole-genome analysis demonstrates that strains classified as pv. pisi actually form a coherent monophyletic clade, so that apparent convergence is actually the product of shared ancestry. We use this example to urge caution when making evolutionary inferences across closely related strains of P. syringae. PMID- 24224665 TI - Molecular identification and expressive characterization of an olfactory co receptor gene in the Asian honeybee, Apis cerana cerana. AB - Olfaction recognition process is extraordinarily complex in insects, and the olfactory receptors play an important function in the process. In this paper, a highly conserved olfactory co-receptor gene, AcerOr2 (ortholog to the Drosophila melanogaster Or83b), cloned from the antennae of the Asian honeybee, Apis cerana cerana Fabricius (Hymenoptera: Apidae), using reverse transcriptase PCR and rapid amplification of cDNA ends. The full-length sequence of the gene was 1763 bp long, and the cDNA open reading frame encoded 478 amino acid residues, including 7 putative transmembrane domains. Alignment analysis revealed that AcerOr2 shares high homology (> 74%) with similar olfactory receptors found in other Hymenoptera species. The amino acid identity with the closely related species Apis mellifera reached 99.8%. The developmental expression analysis using quantitative real-time reverse transcriptase PCR suggested that the AcerOr2 transcript was expressed at a relatively low level in the larval stage, whereas it was expressed broadly in the pupal and adult stages, with a significantly high level on the days just before and after eclosion. In situ hybridization showed that AcerOr2 mRNA was expressed in sensilla placodea and on the basal region of the worker antennal cuticle, in accordance with the previous conclusions that the conserved genes are expressed in most olfactory receptor neurons. PMID- 24224666 TI - Tennessee health plan tobacco cessation coverage. AB - OBJECTIVE: To evaluate the smoking cessation coverage available from public and private Tennessee health plans. DESIGN AND SAMPLE: Cross-sectional study. The sampling frame for private plans was a register of licensed plans obtained from the Tennessee Commerce Department. Government websites and reports provided TennCare data. MEASURES: Data were abstracted from plan manuals and formularies for benefit year 2012. Classification of coverage included comprehensive-all seven recommended medications plus individual and group counseling; moderate-at least two forms of nicotine replacement therapy (NRT) plus bupropion and varenicline and one form of counseling; inadequate-at least one treatment, or none-no medications or counseling, or coverage only for pregnant women. RESULTS: Of nine private plans, one provided comprehensive coverage; two, moderate coverage; four, inadequate coverage, as did TennCare; and two plans provided no coverage. Over 362,800 smokers had inadequate access to cessation treatments under TennCare, while 119,094 smokers had inadequate or no cessation coverage under private plans. CONCLUSION: In 2012, Tennessee fell short of Healthy People goals for total managed care and comprehensive TennCare coverage of smoking cessation. If Tennessee mandates that all health plans provide full coverage, 481,900 smokers may immediately be in a better position to quit. PMID- 24224667 TI - Mental health follow-up among adolescents with suicidal behaviors after emergency department discharge. AB - The objective of this study was to examine mental health follow-up patterns and need for additional urgent ED evaluation in adolescents discharged home from a pediatric ED after an evaluation for suicidal ideation or attempt. In the study, the parent or guardian of suicidal youth ages 11 to 18 years who were discharged from the pediatric ED were interviewed by telephone between 1 and 2 months following the initial visit and asked about their child's suicide risk, mental health follow-up, return ED visits, and previous mental health experiences. ED records were also examined for return visits. A parent or guardian of 100 suicidal adolescents was interviewed by telephone. Most (66%) successfully followed up with a mental health provider. Mental health follow-up was more likely in those with an existing psychiatric diagnosis (OR: 3.03 [95% CI: 1.02 9.05]). The majority of those that returned to the ED within 2 months of their initial evaluation for mental health reasons were admitted [92% (19/21)]. The odds of an ED return visit were increased by a prior inpatient psychiatric admission (OR: 5.23 [95% CI: 1.80-15.16]), and a suicide attempt immediately prior to the initial ED visit (OR: 4.87 [95% CI: 1.04-22.69]). Many suicidal youth who are discharged from the ED successfully follow up with an outpatient mental health provider. However, a significant number do return to the ED within 2 months and require inpatient psychiatric admission. Future ED based interventions should focus on adolescents who attempt suicide and those with a history of prior inpatient admission. PMID- 24224668 TI - Most common methods of suicide in Eastern Mediterranean Region of WHO: a systematic review and meta-analysis. AB - The aim of this study is to determine the frequency of various methods of suicide in Eastern Mediterranean Region by a systematic review and meta-analysis. All published articles in international database were systematically searched before September 2011. In order to analyze the data we used STATA, ver.10 software. We reported proportions with standard errors (SE) for single studies and pooled estimates for proportions of different suicidal methods based on random model meta-analysis. We included 19 articles in the final analysis. The pooled proportion of hanging, self-immolation, and poisoning were 39.7% (95% CI: 26.8% 52.7%), 17.4% (95% CI: 10%-24.8%), and 20.3% (95% CI: 14%-26.5%) respectively. Self-immolation and poisoning were gender dependent and hanging was country dependent in the meta-regression method. We found out that the 3 most common methods of suicide in EMR are hanging, poisoning, and self-immolation. These methods are estimated to account for 77.4% of all methods of suicide in EMR. PMID- 24224669 TI - Retrospective identification of episodes of deliberate self-harm from emergency room registers in general hospitals: an example from Shanghai. AB - The objective of this study was to assess the feasibility of using currently available emergency department (ED) records to retrospectively ascertain the prevalence and characteristics of episodes of medically treated deliberate self harm (DSH). Discussions with ED staff identified 10 ED diagnoses in persons 12 years of age or older that were commonly used for episodes of DSH and another 7 injury-related diagnoses that could, under specific conditions, be acts of DSH. A retrospective analysis of the ED registry of one large general hospital in Shanghai for 2007 to 2010 identified all cases with one of these diagnoses. Diagnosis-specific algorithms based on the characteristics of each case were applied to classify cases as "probable DSH," "possible DSH" or "probably not DSH." The 1,495 cases of DSH identified accounted for 0.2% of all ED admissions over the 4 years; only 6 of them (0.4%) had an ED diagnosis of "suicide attempt." Three ED diagnoses-overdose of medication, fall from height, and pesticide ingestion-accounted for 1,275 (85.3%) of the DSH cases. There were substantial differences in the characteristics of male and female cases of DSH and a 43% drop in the proportion of ED admissions for DSH over the 4 years. In locations where it is not feasible to develop prospective registries of suicide attempts treated in EDs, retrospective analysis of ED records that use algorithms to classify the intentionality of injuries can provide estimates of the prevalence and characteristics of medically treated episodes of DSH. PMID- 24224670 TI - Antidepressant use and method of suicide in the United States: variation by age and sex, 1998-2007. AB - This study examines the association between antidepressant use and suicide rates, by sex, age, and method of suicide, between 1998 and 2007 in the United States. Overall suicide rates for the young and elderly declined but rates for the middle aged increased. All age groups experienced increases in antidepressant use. The elderly exhibited the largest increase in antidepressant usage and biggest declines in suicide rates. Firearm suicides for men and women declined but suicide by drug poisoning rose, particularly for women. For young males and elderly males and females, better treatment of severe depression may have contributed to declining suicide rates. However, rising rates of prescription drug use are associated with higher levels of suicide by drug poisoning. PMID- 24224671 TI - The cessation of deliberate self-harm in a university sample: the reasons, barriers, and strategies involved. AB - Information on how individuals cease deliberate self-harm behaviors, and what they experience as helpful and hindering to this process, was sought in order to optimize and inform treatment. University students (N = 54) with a past history of self-harm were queried about their experience with DSH cessation. Qualitative analysis revealed 6 themes of reasons for DSH cessation, 5 themes of strategies used to cease DSH behaviors, and 4 themes of barriers to cessation. Treatment can be informed by the motivations, strategies, and barriers that individuals experience during the cessation process. The positive strategies that individuals naturally use to cease DSH should be capitalized on in treatment, and the negative strategies should be minimized. PMID- 24224672 TI - Suicide kills more than 10,000 people every year in Bangladesh. AB - This study set out to explore the epidemiology of suicide in Bangladesh. A cross sectional study was carried out during 2003 (January to December). This encompassed a population of 819,429 of all age-groups and sexes. Data was collected by face-to-face interviews at a household level. Suicide was found to be the leading cause of death by injury in the age group of 10-19 years. Adolescent females (10-19 year age group) were found to be the most vulnerable. Overall, the suicide rate was 7.3 (95% CI 5.6-9.5) per 100,000 per year and the highest rate was found in the age group of 60+ years. The rate of suicide was found to be 17-fold higher (95% CI 5.36-54.64) in the rural population, compared to urban rates. Adolescent suicide rate in rural areas was 20.1 (95% CI 12.6 31.7) per 100,000. The rate was 17.7 (95% CI 8.6-34.9) and 22.7(95% CI 12-42) among males and females respectively. Poisoning was found as the most frequent method of suicide. The majority of the suicide victims were found to be very poor and illiterate. Suicide is a major public health problem in Bangladesh. Age, place of residence, economic status and literacy were the major associating factors related to suicide. Adolescents, elderly and those residing in rural regions were the most vulnerable groups. PMID- 24224673 TI - How often, or how many ways: clarifying the relationship between non-suicidal self-injury and suicidality. AB - This study clarified the association of maladaptive, potentially self-damaging behaviors with suicidality. Specifically, we examined whether greater frequency (i.e., how often) or greater versatility (i.e., how many ways) of several self damaging behaviors, including non-suicidal self-injury (NSSI), substance use, and disordered eating, increased risk for suicide. Participants who engaged in NSSI (N = 142) completed questionnaires assessing suicidal and self-damaging behavior at baseline and engagement in suicidal behaviors (e.g., ideation, attempts, talking about suicide) 3 months later. Results suggest that the versatility rather than frequency of self-damaging behaviors is most robustly associated with suicide risk. Engaging in multiple methods of NSSI and using a greater number of illicit substances were positively associated with suicide risk. Further, versatility of NSSI interacted with depression to predict suicide risk at 3-month follow-up such that highly depressed participants who engaged in more methods of NSSI exhibited highest risk, whereas those who engaged in more methods with low depression exhibited the lowest risk. PMID- 24224674 TI - National registration system of suicide behaviors in Iran: barriers and challenges. AB - The present article describes the process of developing a national suicide registry in Iran and evaluates the obstacles in this respect. We established a systematic and uniform portal data collection system in the country and evaluated it from March 2009 for a year. The quality of database and data registration challenges were assessed from different aspects. A total number of 41,109 suicide attempts and 1,338 completed suicides were reported from an area that covered 83.6% of Iran's population in 2009. The rate of suicide attempt was 65.8 per 100,000 people. This study revealed some of the obstacles and challenges of implementing a national registration system. Nationwide suicide registry can serve as a solid foundation for conceptual work, data collection, and preventive interventions. A concerted effort between various organizations is required to efficiently collect data on suicide behaviors. PMID- 24224675 TI - Last suicide attempt before completed suicide in severe depression: an extended suicidal process may be found in men rather than women. AB - The objective of this study was to compare the time from last suicide attempt to suicide in men and women with major depressive disorder with melancholic and/or psychotic features. The case records of 100 suicide victims with severe depression were evaluated. All suicide attempts during the course of depression were noted. The time from last suicide attempt to suicide was compared as well as the occurrence of suicide attempt during the last depressive episode, by gender. Male suicide attempters made fewer suicide attempts than women during their last depressive episode before suicide (8% versus 37%). Men appeared to have a more extended suicidal process from suicide attempt to completed suicide, which ought to be considered in the after-care. PMID- 24224676 TI - Regional brain glucose uptake distinguishes suicide attempters from non attempters in major depression. AB - This study compared regional cerebral metabolic rates of glucose (rCMRglu) determined by [(18)F]-fluoro-2-deoxyglucose positron emission tomography (FDG PET) in suicide attempters and non-attempters. Medication-free patients with major depression (n = 29) had FDG-PET after single-blind administration of placebo (day 1) and fenfluramine (day 2). Suicide attempt history was obtained before scanning and at assessments over 2 subsequent years. Statistical parametric mapping evaluated associations between attempt status and rCMRglu, controlling for age. The study included 13 patients with and 16 without a history of suicide attempt within 2 years before or after scanning. After placebo, rCMRglu in attempters was lower in right dorsolateral prefrontal regions and higher in ventromedial regions than in non-attempters. After fenfluramine, relatively hypometabolic areas enlarged, and no hypermetabolic areas were detected. Distinct rCMRglu patterns may be serotonin-sensitive biomarkers of suicide risk. PMID- 24224677 TI - Suicide by cop: clinical risks and subtypes. AB - This study examines whether clinical classification schemes from general suicide research are applicable for cases of suicide by cop (SbC) and whether there are indicators as to why the police might be engaged in the suicide. Using archival law enforcement data, 13 clinical risks were examined among 68 cases of SbC using exploratory factor analysis and k-means cluster analysis. Three subtypes of SbC cases emerged: Mental Illness, Criminality, and Not Otherwise Specified. The subtypes varied significantly on their levels of mental illness, substance use, and criminal activity. Findings suggest that reducing fragmentation between law enforcement and mental health service providers might be a crucial goal for suicide intervention and prevention, at least among cases of SbC. PMID- 24224678 TI - Association of training on attitudes towards self-injuring clients across health professionals. AB - The objective of this study was to evaluate associations between self-injury training and attitudes across different health care professions. In the study, 342 psychologists, social workers, psychiatric, and medical nurses were recruited from 12 hospitals in Belgium. Participants completed a confidential questionnaire assessing attitudes, perceived knowledge/competence in self-injury, and prior self-injury training. Professionals with training reported more positive empathy, less negative attitudes, and greater perceived knowledge/competence, which was related to positive attitudes. Mental health providers had more positive attitudes than medical professionals. CONCLUSIONS: Attitudes towards self injuring patients are multifaceted and vary across health professions. Training on self-injury should be incorporated into the educational curriculum of all health care professions. PMID- 24224681 TI - The current status of bridging anticoagulation. AB - For patients prescribed chronic vitamin K antagonist therapy requiring a surgical or invasive procedure, the question of whether or not to bridge and how to bridge is commonly encountered in clinical practice. Bridging anticoagulation has evolved over the years and the evidence base for current practice is deficient in many areas. Clinical trials currently being completed with conventional anticoagulants should help strengthen the evidence base for future practice. The availability of novel oral anticoagulants is a welcome addition, though their optimal management peri-procedure is yet to be determined. Prospective multi centre controlled studies that can provide the evidence base for novel oral anticoagulant peri-procedural management are required. PMID- 24224682 TI - Topological effects and binding modes operating with multivalent iminosugar-based glycoclusters and mannosidases. AB - Multivalent iminosugars have been recently explored for glycosidase inhibition. Affinity enhancements due to multivalency have been reported for specific targets, which are particularly appealing when a gain in enzyme selectivity is achieved but raise the question of the binding mode operating with this new class of inhibitors. Here we describe the development of a set of tetra- and octavalent iminosugar probes with specific topologies and an assessment of their binding affinities toward a panel of glycosidases including the Jack Bean alpha mannosidase (JBalphaMan) and the biologically relevant class II alpha mannosidases from Drosophila melanogaster belonging to glycohydrolase family 38, namely Golgi alpha-mannosidase ManIIb (GM) and lysosomal alpha-mannosidase LManII (LM). Very different inhibitory profiles were observed for compounds with identical valencies, indicating that the spatial distribution of the iminosugars is critical to fine-tune the enzymatic inhibitory activity. Compared to the monovalent reference, the best multivalent compound showed a dramatic 800-fold improvement in the inhibitory potency for JBalphaMan, which is outstanding for just a tetravalent ligand. The compound was also shown to increase both the inhibitory activity and the selectivity for GM over LM. This suggests that multivalency could be an alternative strategy in developing therapeutic GM inhibitors not affecting the lysosomal mannosidases. Dynamic light scattering experiments and atomic force microscopy performed with coincubated solutions of the compounds with JBalphaMan shed light on the multivalent binding mode. The multivalent compounds were shown to promote the formation of JBalphaMan aggregates with different sizes and shapes. The dimeric nature of the JBalphaMan allows such intermolecular cross-linking mechanisms to occur. PMID- 24224683 TI - Nanostar and nanonetwork crystals fabricated by in situ nanoparticlization of fully conjugated polythiophene diblock copolymers. AB - Nanostar and nanonetwork crystals were prepared from fully conjugated poly(3-(2 ethylhexyl)thiophene)-block-polythiophene (P3EHT-b-PT) via a simple INCP process. The structural conformation of the nanocrystals was investigated in detail, revealing that with an increase in the block length of PT, the morphology of the nanocrystals changed from nanospheres to nanorods, nanostars, and to nanonetworks. PMID- 24224684 TI - Serial atlas-based diffusion tensor imaging study of uncomplicated mild traumatic brain injury in adults. AB - Abstract In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our aim was to characterize regional and global macro- and microstructural attributes of white matter (WM), gray matter (GM), in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata (CR), corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM, and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time points or between the baseline and follow-up time points within the OC group (p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in the OC group in the global mean diffusivity of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3-month postinjury, as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the CR show insignificant changes in the OC group (p>0.08; N=37). CR radial diffusivity was found to be elevated in the between group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data, which is uncorrected for multiple comparisons, demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the CR. PMID- 24224685 TI - Effects of polarity on the structures and charge states of native-like proteins and protein complexes in the gas phase. AB - Native mass spectrometry and ion mobility spectrometry were used to investigate the gas-phase structures of selected cations and anions of proteins and protein complexes with masses ranging from 6 to 468 kDa. Under the same solution conditions, the average charge states observed for all native-like anions were less than those for the corresponding cations. Using an rf-confining drift cell, similar collision cross sections were measured in positive and negative ion mode suggesting that anions and cations have very similar structures. This result suggests that for protein and protein complex ions within this mass range, there is no inherent benefit to selecting a specific polarity for capturing a more native-like structure. For peptides and low-mass proteins, polarity and charge state dependent structural changes may be more significant. The charged-residue model is most often used to explain the ionization of large macromolecules based on the Rayleigh limit, which defines the upper limit of charge that a droplet can hold. Because ions of both polarities have similar structures and the Rayleigh limit does not depend on polarity, these results cannot be explained by the charged-residue model alone. Rather, the observed charge-state distributions are most consistent with charge-carrier emissions during the final stages of analyte desolvation, with lower charge-carrier emission energies for anions than the corresponding cations. These results suggest that the observed charge-state distributions in most native mass spectrometry experiments are determined by charge-carrier emission processes; although the Rayleigh limit may determine the gas-phase charge states of larger species, e.g., virus capsids. PMID- 24224686 TI - Response to: 'On the use of Glasgow Coma Scale as a predictor of intensive care unit admission in deliberate drug poisoning'. PMID- 24224687 TI - Patients' and physicians' perspectives on opioid therapy for chronic cancer and musculoskeletal pain in Germany, Italy, and Turkey: PAin RESearch (PARES) survey. AB - OBJECTIVE: Under-treatment or lack of appropriate treatment for chronic pain remains an ongoing major healthcare problem. Opioids are being increasingly recognized as an effective option for chronic pain management. The objective of this survey was to understand the perspective of patients treated with opioids on quality of treatment, preferences, and possibilities to improve treatment and communication between patients and physicians. RESEARCH DESIGN: A large-scale PAin RESearch (PARES) survey of 2860 patients (Germany, Italy, and Turkey) with chronic cancer or musculoskeletal pain prescribed opioid therapy was conducted to assess various factors such as ease of use and compliance, sleep, quality-of life, and polymedication. A physician component was also included. Relationships between variables and differences between groups were tested using Spearman and Wilcoxon signed-rank tests, respectively. RESULTS: Of the patients surveyed, 61% received strong opioids (WHO III) and 39% weak opioids (WHO II). Nearly 65% of the patients were currently on a twice daily or more dosing schedule; however, 61.5% of the patients responded that they considered once-daily dosing to be the most convenient schedule. Patients' responses indicated that different dosing schedules significantly influenced the occurrence of end-of-dose pain, feeling limited by the remaining level of pain, problems in falling asleep, and episodes of waking up at night or early in the morning. Physicians' responses showed that they were not surprised by 68.5% of patient responses; they also felt the need to change some aspect of pain treatment for a third of the patients, the commonest being pain medication (52.4%). CONCLUSIONS: The results of the survey suggest that patients prefer a convenient dosing scheme, which may have a positive impact on compliance. Physicians may have to communicate more closely with patients about their needs. PMID- 24224689 TI - Recurrence of gastroesophageal reflux disease correlated with a short dinner-to bedtime interval. AB - BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) can be classified into erosive reflux disease (ERD) and nonerosive gastroesophageal reflux disease (NERD). We aimed to compare the recurrence rates of ERD and NERD and determine the risk factors related to the recurrence. METHODS: This prospective study comprised 337 consecutive adults who completed questionnaires on their GERD symptoms, height, weight, sleeping position, dinner time, and bedtime. During upper gastrointestinal endoscopy, the presence of a hiatal hernia and mucosal breaks in the low esophagus, esophageal length (the distance between the Z-line and the incisors), and the esophageal length-to-height ratio were recorded. Recurrence was diagnosed when the patient required additional proton pump inhibitor medication after initial recovery with 4-8 weeks of treatment. RESULTS: Recurrence was experienced by 47 (26.0%) of 181 GERD patients. The recurrence rate did not differ between the 48 ERD (27.1%) and 133 NERD (25.6%) patients (P = 0.849). Of the various factors studied, recurrence was found to be correlated with a dinner-to-bedtime interval of less than 3 h (P = 0.002), globus sensation (P = 0.031), and old age (P = 0.047). Logistic regression analysis revealed that a short interval between dinner and bedtime was the only factor significantly related to the recurrence (P = 0.002). CONCLUSION: Both ERD and NERD patients who sleep within 3 h after eating have a higher risk of GERD recurrence. Our findings highlight the impact of a short dinner-to-bedtime interval on the recurrence of GERD (ClinicalTrials.gov ID: KCT0000134). PMID- 24224690 TI - Differences in the intrinsic immunogenicity and allergenicity of Bet v 1 and related food allergens revealed by site-directed mutagenesis. AB - BACKGROUND: Birch pollen allergies are frequently associated with adverse reactions to various fruits, nuts, or vegetables, described as pollen-food syndrome (PFS) and caused by cross-reactive IgE antibodies primarily directed against Bet v 1. Specific immunotherapy (SIT) represents an effective treatment for inhalant allergies; however, successful birch pollen SIT does not correlate well with the amelioration of concomitant food allergies. METHODS: As vaccine candidates, apple Mal d 1 as well as hazelnut Cor a 1 derivatives were designed by in silico backbone analyses of the respective allergens. The proteins were produced by site-directed mutagenesis as fold variants of their parental allergens. Because Mal d 1 and Cor a 1 form cysteine-mediated aggregates, nonaggregative cysteine to serine mutants were also generated. The proteins were characterized physicochemically, immunologically, and in in vivo models with or without adjuvant. RESULTS: The structurally modified proteins showed significantly decreased IgE binding capacity. Notably, both in vivo models revealed reduced immunogenicity of the hypoallergenic fold variants. When formulated with alum, the monomeric cysteine mutants induced a similar immune response as the aggregated parental allergens, which is in contrast with data published on Bet v 1. CONCLUSION: These findings lead to the suggestion that the Bet v 1 structure has unique intrinsic properties, which could account for its high allergenicity. Obviously, these characteristics are not entirely shared with its food homologues from apple and hazelnut. Thus, it is important to tackle pollen-related food allergies from different angles for the generation of effective vaccine candidates to treat birch PFS. PMID- 24224691 TI - Quality indicators for initial licensure and discipline in nursing laws in South Korea and North Carolina. AB - BACKGROUND: The Korean regulatory framework of nursing licensure reflects that of the USA, but its content differs in some of the powers related to quality assurance. AIM: This article compares regulatory quality indicators and describes core standards in nursing regulations that are related to both initial licensure and discipline for three groups: the National Council of State Boards of Nursing, the North Carolina and the South of Korea. METHODS: A descriptive, comparative law design is used to examine the differences and similarities in the quality indicators and core standards found in three documents: the National Council of State Boards of Nursing Model Act, the North Carolina Nursing Practice Act and the Korean Medical Service Act for registered nurses. RESULTS: The findings indicate that ten quality indicators and two standards appear in study objects. Although most of the quality indicators are common to all documents, some differences are found in terms of the scope of criminal background checks and the range of grounds for disciplinary action. LIMITATIONS: These findings cannot be generalized in the USA because although the North Carolina nursing act was selected as an example of US nursing laws, nursing laws differ somewhat across states. CONCLUSIONS: This comparative study shows a clear opportunity to develop indicators that acknowledge the important areas of competence and good moral character and how they can improve patient safety in Korea. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study provides recommendations for Korean nursing legislative redesign and pointers for other jurisdictions to consider. PMID- 24224692 TI - Where there is smoke there is fire: the Iranian system of paid donation. PMID- 24224693 TI - Discovery of 1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1 sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor antagonist with significant weight-loss efficacy in diet-induced obese mice. AB - After extensive synthetic efforts, we found that many structurally diverse bioisosteres could be generated via derivatizing the C-4 alkyl chain on the pyrazole ring of compound 3 (B/P = 1/33) with different electronegative groups. Especially when a sulfonamide or sulfamide moiety was added, resulting compounds exhibited not only potent CB1R activity but also a desired tPSA value over 90 A(2), a threshold considered to possess a low probability to cross BBB, leading to the identification of compound 4 (B/P = 1/64) as a peripherally restricted CB1R antagonist. Apart from its significant weight-loss efficacy in DIO mice, compound 4 also displays 163 clean off-target profiles and is currently under development for treating obesity and the related metabolic syndrome. PMID- 24224695 TI - Nickel-catalyzed aromatic C-H alkylation with secondary or tertiary alkyl-bromine bonds for the construction of indolones. AB - A nickel-catalyzed aromatic C-H alkylation with tertiary or secondary alkyl-Br bonds for the construction of indolones was demonstrated. Various functional groups were well tolerated. Moreover, the challenging secondary alkyl bromides were well introduced in this transformation. Radical trapping and photocatalysis conditions exhibited that it is most likely to be a radical process for this aromatic C-H alkylation. PMID- 24224694 TI - Very low carbohydrate diet significantly alters the serum metabolic profiles in obese subjects. AB - Emerging evidence has consistently shown that a very low carbohydrate diet (VLCD) can protect against the development of obesity, but the underlying mechanisms are not fully understood. Here we applied a comprehensive metabonomics approach using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to study the effects of an 8-week dietary intervention with VLCD on serum metabolic profiles in obese subjects. The VLCD intervention resulted in a weight loss and significantly decreased homeostasis model assessment-insulin resistance. The metabonomics analysis identified a number of differential serum metabolites (p < 0.05) primarily attributable to fatty acids, amino acids including branched chain amino acids, amines, lipids, carboxylic acids, and carbohydrates in obese subjects compared to healthy controls. The correlation analysis among time, VLCD intervention, and clinical parameters revealed that the changes of metabolites correlated with the changes of clinical parameters and showed differences in males and females. Fatty acids, amino acids, and carboxylic acids were increased in obese subjects compared with their normal healthy counterparts. Such increased levels of serum metabolites were attenuated after VLCD intake, suggesting that the health beneficial effects of VLCD are associated with attenuation of impaired fatty acid and amino acid metabolism. It also appears that VLCD induced significant metabolic alterations independent of the obesity-related metabolic changes. The altered metabolites in obese subjects post-VLCD intervention include arachidonate, cis-11,14-eicosadienoate, cis-11,14,17-eicosatrienoate, 2 aminobutyrate, acetyl-carnitine, and threonate, all of which are involved in inflammation and oxidation processes. The results revealed favorable shifts in fatty acids and amino acids after VLCD intake in obese subjects, which should be considered biomarkers for evaluating health beneficial effects of VLCD and similar dietary interventions. PMID- 24224696 TI - Maternal territoriality achieved through shaking and lunging: an investigation of patterns in associated behaviors and substrate vibrations in a colonial embiopteran, Antipaluria urichi. AB - Substrate vibration communication is displayed by a variety of insects that rely on silk for shelter. Such signaling is often associated with territoriality and social interactions. The goal in this study was to explore the use of substrate vibration by subsocial insects of the little-studied order Embioptera (also known as Embiidina). Antipaluria urichi (Saussure) (Embioptera: Clothodidae) from Trinidad and Tobago, a large embiopteran, exhibits maternal care and facultatively colonial behavior. Previous observations suggested that they were aggressive while guarding eggs but gregarious when not. Egg-guarders in particular have been observed shaking and lunging their bodies, but to date these putative signals have not been recorded nor were their contexts known. Staged interactions were conducted in the laboratory using residents that had established silk domiciles enveloping piezo-electric film used to detect vibrations. Predictions from two competing hypotheses, the maternal territoriality hypothesis and the group cohesion hypothesis, were erected to explain the occurrence of signaling. Experiments pitted pre-reproductive and egg guarding residents against female and male intruders, representing social partners that ranged from potentially threatening to innocuous or even helpful. Behavioral acts were identified and scored along with associated substrate vibrations, which were measured for associated body movements, duration, and frequency spectra. Signals, sorted by the distinct actions used to generate them, were lunge, shake, push up, and snapback. Egg-guarding females produced most signals in response to female intruders, a result that supported the maternal territoriality hypothesis. Female intruders generally responded to such signaling by moving away from egg-guarding residents. In contrast, pre-reproductive residents did not signal much, and intruders settled beside them. Theme software was used to analyze the behavioral event recordings to seek patterns over time and their association with signals. Long patterns of behavioral acts were associated with shakes, lunges, and push-ups, indicating that interactions were occurring between the residents and intruders as would be expected when communication occurs. The value of Theme software, as well as the relationship between signaling by A. urichi and the risks and benefits of coloniality, are discussed. PMID- 24224697 TI - Thin lenticule Descemet's stripping automated endothelial keratoplasty: single, slow pass technique. AB - BACKGROUND: To evaluate the outcomes of single pass thin lenticule sutureless Descemet's stripping automated endothelial keratoplasty with donor lenticules prepared using a 400 MUm microkeratome head. DESIGN: Interventional case series. PARTICIPANTS: Cases with corneal endothelial dysfunction. METHODS: Fifteen cases with corneal endothelial dysfunction (eight pseudophakic bullous keratopathy, three Fuchs' endothelial dystrophy, three congenital hereditary endothelial dystrophy and one failed graft) underwent thin lenticule Descemet's stripping automated endothelial keratoplasty at a tertiary care hospital. Donor lenticule was prepared with a single pass 400 MUm Carriazo Barraquer microkeratome (Moria, Antony, France) head. Sutureless Descemet's stripping automated endothelial keratoplasty was performed in all the cases through a 3.5 mm corneoscleral tunnel using a Busin glide for graft insertion. MAIN OUTCOME MEASURES: Main parameters evaluated were postoperative donor lenticule thickness and best-corrected visual acuity. RESULTS: Donor lenticules were harvested successfully for all 15 cases without any complications. At 6-months follow up, the mean logMAR best-corrected visual acuity improved from 1.87 +/- 0.52 to 0.109 +/- 0.11 (P = < 0.0001). The mean donor lenticule thickness was 111 +/- 17.62 MUm (range 70-134 MUm) at the last follow up. The mean endothelial cell loss was 26.33 +/- 1.34%. CONCLUSIONS AND RELEVANCE: Thin donor lenticules for Descemet's stripping automated endothelial keratoplasty can be safely harvested using a single pass technique with 400 MUm microkeratome head and can be used for a successful Descemet's stripping automated endothelial keratoplasty surgery. PMID- 24224698 TI - Intra-operative hyperthermia in a cat with a fatal outcome. AB - HISTORY: A four year old male neutered Domestic Short Hair cat presented for general anaesthesia for hind limb orthopaedic surgery. The cat had been anaesthetized four days previously with propofol and isoflurane and made an uneventful recovery. PHYSICAL EXAMINATION AND MANAGEMENT: On pre-anaesthetic examination the cat had a temperature of 38.9 degrees C and was otherwise healthy. After a premedication of acepromazine and pethidine, anaesthesia was induced with thiopental and maintained with isoflurane in oxygen 50% and nitrous oxide 50%. Increases in heart rate, respiratory rate, end tidal carbon dioxide tension and temperature were observed, occurring sequentially, from 110 to 175 minutes after anaesthetic induction. Despite ceasing all warming measures and attempting to cool the patient, body temperature continued to rapidly rise, reaching 42.5 degrees C and limb rigidity was observed. Isoflurane administration was stopped and esmolol was administered. Cardiac arrest occurred. Cardio-pulmonary cerebral resuscitation was commenced and a lateral thoracotomy was performed to allow cardiac compressions and internal defibrillation. Atropine, adrenaline, glucose and dopamine were administered and cold saline was instilled into the thoracic cavity. FOLLOW-UP: Resuscitation was unsuccessful and the cat died. CONCLUSIONS: A presumptive diagnosis of malignant hyperthermia was made. Malignant hyperthermia should be considered, even if prior exposure to volatile inhalational anaesthesia was uneventful, and prompt and aggressive therapy instituted. PMID- 24224699 TI - De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. AB - Structural characterization of highly sulfated glycosaminoglycans (GAGs) by collisionally activated dissociation (CAD) is challenging because of the extensive sulfate losses mediated by free protons. While removal of the free protons may be achieved through the use of derivatization, metal cation adducts, and/or electrospray supercharging reagents, these steps add complexity to the experimental workflow. It is therefore desirable to develop an analytical approach for GAG sequencing that does not require derivatization or addition of reagents to the electrospray solution. Electron detachment dissociation (EDD) can produce extensive and informative fragmentation for GAGs without the need to remove free protons from the precursor ions. However, EDD is an inefficient process, often requiring consumption of large sample quantities (typically several micrograms), particularly for highly sulfated GAG ions. Here, we report that with improved instrumentation, optimization of the ionization and ion transfer parameters, and enhanced EDD efficiency, it is possible to generate highly informative EDD spectra of highly sulfated GAGs on the liquid chromatography (LC) timescale, with consumption of only a few nanograms of sample. We further show that negative electron transfer dissociation (NETD) is an even more effective fragmentation technique for GAG sequencing, producing fewer sulfate losses while consuming smaller amount of samples. Finally, a simple algorithm was developed for de novo HS sequencing based on their high-resolution tandem mass spectra. These results demonstrate the potential of EDD and NETD as sensitive analytical tools for detailed, high-throughput, de novo structural analyses of highly sulfated GAGs. PMID- 24224700 TI - Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign. AB - Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab-Indian (AI) HBB (beta-globin gene) haplotype. The phenotype of AI SCD in children was described as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital-based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety-six per cent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co-inherited alpha-thalassaemia and about one-third had glucose-6 phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F-cells. PMID- 24224702 TI - Dinitrogen release from arylpentazole: a picosecond time-resolved infrared, spectroelectrochemical, and DFT computational study. AB - p-(Dimethylamino)phenyl pentazole, DMAP-N5 (DMAP = Me2N-C6H4), was characterized by picosecond transient infrared spectroscopy and infrared spectroelectrochemistry. Femtosecond laser excitation at 310 or 330 nm produces the DMAP-N5 (S1) excited state, part of which returns to the ground state (tau = 82 +/- 4 ps), while DMAP-N and DMAP-N3 (S0) are generated as double and single N2 loss photoproducts with eta ~ 0.14. The lifetime of DMAP-N5 (S1) is temperature and solvent dependent. [DMAP-N3](+) is produced from DMAP-N5 in a quasireversible, one-electron oxidation process (E1/2 = +0.67 V). Control experiments with DMAP-N3 support the findings. DFT B3LYP/6-311G** calculations were used to identify DMAP-N5 (S1), DMAP-N3(+), and DMAP-N in the infrared spectra. Both DMAP-N5 (S1) and [DMAP-N5](+) have a weakened N5 ring structure. PMID- 24224703 TI - Pain: a quality of care issue during patients' admission to hospital. AB - AIM: To determine the extent of clinically significant pain suffered by hospitalized patients during their stay and at discharge. BACKGROUND: The management of pain in hospitals continues to be problematic, despite long standing awareness of the problem and improvements, e.g. acute pain teams and patient-controlled analgesia, epidural analgesia. Poorly managed pain, especially acute pain, often leads to adverse physical and psychological outcomes including persistent pain and disability. A systems approach may improve the management of pain in hospitals. DESIGN: A descriptive cross-sectional exploratory design. METHOD: A large electronic pain score database of vital signs and pain scores was interrogated between 1st January 2010 and 31st December 2010 to establish the proportion of hospital inpatient stays with clinically significant pain during the hospital stay and at discharge. FINDINGS: A total of 810,774 pain scores were analysed, representing 38,451 patient stays. Clinically significant pain was present in 38.4% of patient stays. Across surgical categories, 54.0% of emergency admissions experienced clinically significant pain, compared with 48.0% of elective admissions. Medical areas had a summary figure of 26.5%. For 30% patients, clinically significant pain was followed by a consecutive clinically significant pain score. Only 0.2% of pain assessments were made independently of vital signs. CONCLUSION: Reducing the risk of long-term persistent pain should be seen as integral to improving patient safety and can be achieved by harnessing organizational pain management processes with quality improvement initiatives. The assessment of pain alongside vital signs should be reviewed. Setting quality targets for pain are essential for improving the patient's experience. PMID- 24224701 TI - Hepatocyte growth factor in dampening liver immune-mediated pathology in acute viral hepatitis without compromising antiviral activity. AB - BACKGROUND AND AIM: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis. METHODS: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune mediated liver damage were evaluated. We studied dendritic cell (DC) activation in the presence of HGF. T cells collected from infected mice were restimulated with virally infected DC to measure cytokine production in vitro. RESULTS: HGF ameliorated the liver inflammation during viral hepatitis as alanine transferase, intrahepatic lymphocytes, and splenocyte counts were diminished by HGF. Lower histological scores of liver pathology were observed in the HGF group. DC from the HGF group expressed reduced CD40. The hepatic expression and serum concentration of IL-12p40 were diminished in HGF-transfected mice. In vitro experiments with DC confirmed that HGF diminished CD40 expression and IL-12p40 production. The expression and serum levels of IFN-gamma, IL-6 and CXCL9 were significantly decreased in the HGF group. HGF overexpression diminished the expression and concentration of IL-10 and TGF-beta. The frequency of PD-1(+) Tim 3(+) in CD8 T cells was decreased by HGF overexpression. Moreover, T cells in the HGF group at day 14 secreted more IFN-gamma and TNF-alpha than those in the control group when restimulated with virally infected DC. CONCLUSION: HGF modulated DC activation and T cell priming, thereby limiting the immune-mediated damage in the liver. However, viral clearance was not compromised by HGF. PMID- 24224704 TI - The genotoxic and antigenotoxic effects of Salvia fruticosa leaf extract in human blood lymphocytes. AB - The aim of this study was to investigate the genotoxic and antigenotoxic effects of Salvia fruticosa (Sf) leaf extract with the absence and presence of S9 mix using sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) formation test systems in human peripheral blood lymphocytes (HPBLs) that were treated with 1.5-, 3.0- and 6.0-uL/mL concentrations for 24- and 48-hour treatment periods. The cytotoxicity of Sf leaf extract was also investigated by calculating the mitotic index (MI), proliferation index (PI) and nuclear division index (NDI). In the absence of S9 mix, Sf leaf extract alone increased SCE frequency at the 48-hour treatment period; however, it induced the CA and MN at all concentrations and at all treatment periods. Sf plus MMC (mitomycin C) synergically induced SCE and CA, except the highest concentration of Sf leaf extract and MMC on induction of SCE. In addition, Sf leaf extract induced the effect of MMC on MN frequency for 24 hours, but it significantly decreased the effect of MMC on MN frequency for the 48-hour treatment period. Sf leaf extract showed a cytotoxic effect by decreasing the MI; however, it did not decrease the PI and NDI. In the presence of S9 mix, Sf leaf extract did not increase the SCE, when compared to solvent control, whereas it reduced the effect of cyclophosphamide (Cyp). Sf leaf extract induced the CA and MN, but could not increase the effect of Cyp on CA and MN formation. Sf leaf extract had no cytotoxic effect; however, it induced the cytotoxicity of Cyp. PMID- 24224705 TI - Devising a competency-based continuing professional development programme to meet the needs of on-call consultant paediatricians. AB - AIM: To define the clinical competencies currently required by on-call consultant paediatricians in Sweden and to describe how these competencies can be acquired by using an outcome-based continuing professional development (CPD) programme. METHODS: The overall aims and objectives of the programme were formulated to meet the current responsibilities of an on-call consultant. It was delineated during a precourse needs assessment of 26 consultants, before being implemented with 16 participants, using a variety of learning, assessment and evaluation methods. RESULTS: The precourse needs assessment identified 217 clinical situations and 17 themes, and 139 subthemes were developed. During the programme evaluation, carried out using a reflective questionnaire, participants stated that they had improved their understanding of the role of, and demands on, the on-call consultant. They had also felt more confident on-call, had built a network of colleagues and updated their knowledge in relevant fields. CONCLUSION: We defined and implemented a competency-based CPD programme to meet the changing demands faced by on-call consultant paediatricians. The aims and objectives of the programme were formulated according to a needs assessment among consultant paediatricians active in on-call services. Evaluation of the programme indicates that participants moved in the direction of the overall objectives. PMID- 24224706 TI - Comprehensive assessment of isolated traumatic subarachnoid hemorrhage. AB - Recent studies have shown that isolated traumatic subarachnoid hemorrhage (tSAH) in the setting of a high Glasgow Coma Scale (GCS) score (13-15) is a relatively less severe finding not likely to require operative neurosurgical intervention. This study sought to provide a more comprehensive assessment of isolated tSAH among patients with any GCS score, and to expand the analysis to examine the potential need for aggressive medical, endovascular, or open surgical interventions in these patients. By undertaking a retrospective review of all patients admitted to our trauma center from 2003-2012, we identified 661 patients with isolated tSAH. Only four patients (0.61%) underwent any sort of aggressive neurosurgical, medical, or endovascular intervention, regardless of GCS score. Most tSAH patients without additional systemic injury were discharged home (68%), including 53% of patients with a GCS score of 3-8. However, older patients were more likely to be discharged to a rehabilitation facility (p<0.01). There were six (1.7%) in-hospital deaths, and five patients of these patients were older than 80 years old. We conclude that isolated tSAH, regardless of admission GCS score, is a less severe intracranial injury that is highly unlikely to require aggressive operative, medical, or endovascular intervention, and is unlikely to be associated with major neurologic morbidity or mortality, except perhaps in elderly patients. Based upon our findings, we argue that impaired consciousness in the setting of isolated tSAH should strongly compel a consideration of non traumatic factors in the etiology of the altered neurological status. PMID- 24224707 TI - Secreted Wnt antagonists during eradication of cytomegalovirus infection in solid organ transplant recipients. AB - We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection. PMID- 24224708 TI - Why do we sleep so late? PMID- 24224712 TI - Shallot aphids, Myzus ascalonicus, in strawberry: biocontrol potential of three predators and three parasitoids. AB - The parasitization capacity of 3 parasitoids and the predation capacity of 3 predators towards the shallot aphid, Myzus ascalonicus Doncaster (Homoptera: Aphididae), on strawberry, Fragaria x ananassa Duchesne (Rosales: Rosaceae) cv. Honeoye, were examined in laboratory experiments. In Petri dish assays, both Aphidius colemani Viereck (Hymenoptera: Aphidiidae) and A. ervi Haliday readily stung shallot aphids, with no significant difference in stinging frequency between the two species. A. ervi induced a significantly higher mortality (79.0 +/- 7.2%) in terms of stung aphids compared with A. colemani (55.3 +/- 4.1%); however, only a minor fraction (2.7 +/- 1.8% and 7.1 +/- 3.1%, respectively) of the killed aphids resulted in formation of mummies, presumably due to a physiological response to parasitism. The low percentage of mummification precludes the use of either Aphidius species in anything but inundative biocontrol. In similar set-ups, Aphelinus abdominalis (Dalman) (Hymenoptera: Aphelinidae) killed almost half (49.6 +/- 5.3%) of the exposed aphids through host feeding. In addition, 23.2 +/- 7.3% of non-host-fed aphids developed into mummified aphids, and 38.1 +/- 13.2% of non-host-fed aphids died from other parasitoid-induced causes. However, the host feeding rate was reduced to only 1.2 +/- 0.8%, and no significant parasitization mortality was observed on strawberry plants, suggesting that host plants interfered with A. abdominalis activity. This parasitoid does not, therefore, seem to be suited to either inoculative or inundative biocontrol of shallot aphids in strawberry. The three predators studied were the green lacewing, Chrysoperla carnea Steph. (Neuroptera: Chrysopidae), the two-spotted lady beetle, Adalia bipunctata L. (Coleoptera: Coccinellidae), and the gall midge Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae). Third instars of all 3 predators readily preyed upon the shallot aphid in Petri dish set-ups with significant differences in daily predation (34.62 +/- 3.45, 25.25 +/- 3.18, and 13.34 +/- 1.45, respectively). Further studies on A. bipunctata revealed that the larvae maintained their daily predation capacity (32.0 +/- 6.3) on strawberry plants. About 60% of already ovipositing A. bipunctata refrained from laying any eggs on the first day after transfer to set-ups with combinations of shallot or peach-potato aphids, Myzus persicae (Sulzer) (Homoptera: Aphididae), and strawberry or sweet pepper leaves. The aphid species and the plant species did not, however, have a significant influence on the number of females laying eggs, the average number of eggs laid during the first day being 6.37+/-1.28 per female. Adult lady beetles had a significant preference for odor from controls without plants over odors from uninfested strawberry or pepper plants, but they showed no preference for either of the plant species, whether infested with aphids or not. The predation capacity of A. bipunctata on shallot aphids holds promise for its use in inundative biocontrol, and the results on egg laying cues suggests that inoculative biocontrol may be possible, although further studies will be needed for a complete evaluation. PMID- 24224715 TI - Tetraalkylammonium-templated stereoselective Norrish-Yang cyclization. AB - Tetrabutylammonium salts serve as templates for the Norrish-Yang cyclization of 2 benzyloxy-acylbenzenes to give trans-dihydrobenzofuranols in high stereoselectivities. The dual cation-pi interactions between an ammonium with a benzene ring and a carbonyl group play a key role in changing the conformation of the substrate, which was supported by ab initio calculations. PMID- 24224716 TI - Editorial Comment to Health-related quality of life after carbon-ion radiotherapy for prostate cancer: a 3-year prospective study. PMID- 24224717 TI - Genetic variation in toll-like receptors and retinoic acid-inducible gene I and outcome of hepatitis C virus infection: a candidate gene association study. AB - We evaluated the effects of genetic variation in toll-like receptors (TLR), retinoic acid-inducible gene I (RIG-I) and their signalling pathways on spontaneous hepatitis C virus (HCV) resolution. We screened 95 single-nucleotide polymorphisms (SNPs) in 22 genes. SNPs significantly associated with resolution in the discovery cohort were genotyped in a validation cohort. Multivariate logistic regression adjusted for sex, hepatitis B surface antigen, HIV infection and the interleukin-28B rs12979860 SNP was performed in the combined cohort. Haplotype reconstruction and linkage disequilibrium analysis were performed. srs2233437, rs730775 and rs28362857 in Inhibitor of NF-kB epsilon (IkBepsilon) and rs352140 in TLR9 were associated with spontaneous HCV resolution (P <= 0.05) in the discovery cohort (n = 308). In the validation cohort (n = 216), we replicated a significant association with HCV resolution for two SNPs in the IkBepsilon, rs2233437 and rs730775. Presence of one or two of the variant allele in rs2233437 had more than twofold higher odds of resolution in adjusted logistic regression (adjusted odds ratio (aOR), 2.6; (95% CI, 1.4, 4.8) P = 0.002). We identified polymorphisms in the IkBepsilon gene associated with spontaneous HCV resolution in two independent cohorts. PMID- 24224718 TI - Minimal RED cell pairs markedly improve electrode kinetics and power production in microbial reverse electrodialysis cells. AB - Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m(2)-cat) and wastewater (WW: 0.3 to 1.7 W/m(2)), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m(2); WW: 1.9 W/m(2)). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1 CP (Acetate: 3.1 W/m(2)-mem; WW: 1.7 W/m(2)) and 2-CP (Acetate: 1.3 W/m(2)-mem; WW: 0.6 W/m(2)) reactors were much higher than previous MRCs (0.3-0.5 W/m(2)-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. PMID- 24224719 TI - Building an integrated research/policy planning age-friendly agenda. AB - This article describes an innovative model for integrating research into a policy and planning agenda aimed to help neighborhoods become more supportive of older adults. Philadelphia Corporation for Aging (PCA) established Age-Friendly Philadelphia (AFP) to catalyze efforts to improve the physical and social environments for seniors. The Research Program at PCA became an important part of this effort by providing multiple types of supports to PCA staff and other stakeholders. Most notably, the research program worked with planners to adopt the United States Environmental Protection Agency's Aging Initiative model for Philadelphia. That model focuses on (1) staying active, connected, and engaged; (2) development and housing; (3) transportation and mobility; and (4) staying healthy. Examples of practice efforts actualized using this research are also presented. By developing a new approach to the way research can support practice initiatives, AFP has been able to increase its effectiveness, and researchers have found better ways to work collaboratively with professionals in policy, planning, and practice. The PCA model should be considered as a framework for similar efforts aimed at creating age-friendly communities. PMID- 24224720 TI - Primary mesh repair of Amyand's hernia. PMID- 24224721 TI - Professor John Scott, folate and neural tube defects. AB - John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. PMID- 24224722 TI - Doxorubicin-eluting beads versus conventional transarterial chemoembolization for the treatment of hepatocellular carcinoma. AB - BACKGROUND AND AIM: Doxorubicin-eluting bead transarterial chemoembolization (DEB TACE) is a novel locoregional treatment for unresectable hepatocellular carcinoma (HCC). However, to date, the benefits of DEB-TACE versus conventional transarterial chemoembolization (TACE) remain unclear. This meta-analysis was conducted to evaluate the efficacy and safety of the two treatments for patients with unresectable HCC. METHODS: We searched for relevant articles by means of computerized bibliographic search and complementary manual search. Objective tumor response, overall survival, and adverse events were then calculated and analyzed. RESULTS: A total of seven clinical studies with 700 participants were included in the current meta-analysis. Significantly better objective tumor response was found for DEB-TACE than for conventional TACE (OR = 1.92, 95% CI [1.34, 2.77]; P = 0.0004), with relative risk difference of 0.15 [0.07, 0.24] (P = 0.0003). One-year and 2-year survival rates were statistically significantly higher for DEB-TACE compared with conventional TACE (Peto OR, 95% CI: 0.64 [0.46, 0.89], P = 0.007; 0.61 [0.47, 0.80], P = 0.0003, respectively). Peto ORs of 6 month and 3-year survival were 0.72 [0.46, 1.14] (P = 0.16) and 0.77 [0.55, 1.06] (P = 0.11), respectively, showing no difference statistically. However, we could still find a tendency favoring DEB-TACE. Adverse side effects were similar in both groups, with postembolization syndrome occurring most commonly. CONCLUSIONS: This meta-analysis shows that DEB-TACE provides significantly better tumor response compared with conventional TACE. One-year and 2-year survival are better with DEB-TACE. In addition, DEB-TACE is as safe as conventional TACE. Therefore, DEB-TACE is a better choice for HCC patients for whom curative treatments like liver transplantation and liver resection are not suitable. PMID- 24224723 TI - A novel flow partition device for spirometry during large animal anaesthesia. AB - OBJECTIVE: We describe and test a novel device for large animal anaesthesia monitoring that uses standard human medicine spirometry sensors. STUDY DESIGN: In vitro study. METHODS: The device consists of two adapters that enable the flow to be split evenly into four tubes in parallel, each tube containing a D-lite sensor. The performance of this flow partitioning device (FPD) over a range of flows from 100 to 700 L minute-1 was determined and the pressure versus flow relation, resistance and dead space was compared with a Horse-lite (Moens 2010). RESULTS: Equipped with four D-lite sensors, and a flow of 700 L minute-1 the pressure drop of the FPD was 13.5 cm H2O, resistance 1.17 cm H2O second L-1 and volume (potential dead space) 182 mL, compared to 2.8 cm H2O, 0.24 cm H2O second L-1 and 54 mL respectively for the Horse-lite. The predicted value of the flow partition of 1/4 could be confirmed. Limits of agreement were found to be 4.2% in inspiratory direction and 7.1% in expiratory direction. CONCLUSIONS AND CLINICAL RELEVANCE: The FPD is an affordable device that extends the specification of any commercially available human spirometry sensors to large animal applications. However, an increase in total resistance and dead space has to be taken into account. Therefore, the new device could be useful during equine anaesthesia. PMID- 24224724 TI - Study of the distribution of active caspase-3-positive cells in turbot, Scophthalmus maximus (L.), enteromyxosis. AB - Enteromyxosis caused by Enteromyxum scophthalmi is one of the parasitizations with a higher economic impact on turbot, Scophthalmus maximus (L.), aquaculture. This myxosporean produces severe catarrhal enteritis with abundant inflammatory infiltrates in the lamina propria-submucosa (LP), epithelial detachment and leucocyte depletion of the lymphohaematopoietic organs. Some advances made on the pathogenesis pointed to a role of apoptosis in the enteromyxosis. Therefore, the main aim of this work was to employ the TUNEL assay and the anti-(active caspase 3) immunohistochemical assay to detect apoptotic cells in both healthy and E. scophthalmi-infected turbot in order to establish the presence and distribution of apoptotic cells during development of the disease. More apoptotic cells located within the gastrointestinal epithelium were observed in the initial stages of the infection in E. scophthalmi-infected turbot compared with non infected turbot. As the infection progressed, a higher degree of apoptosis occurred in the epithelium of folds heavily parasitized. In the severely infected turbot, apoptosis was also found among the leucocytes of the intestinal inflammatory infiltrates. Moreover, the number of active caspase-3-positive cells in the lymphohaematopoietic organs tended to increase with disease severity. In view of the results, increased apoptosis in the epithelium may favour the scaling that occurs during enteromyxosis and cell death of leucocytes in the intestinal LP, contributing to leucocyte depletion in severe cases. PMID- 24224725 TI - In silico and in vitro genotoxicity evaluation of descarboxyl levofloxacin, an impurity in levofloxacin. AB - It is important to establish the safety of impurities in drug substances or drug products. The assessment of genotoxicity of impurities and the determination of acceptable limits for genotoxic impurities was addressed in some recent guidances as a difficult issue. Descarboxyl levofloxacin is an impurity isolated from levofloxacin, which may impose a risk without associated benefit. However, there is insufficient toxic information about descarboxyl levofloxacin. This study investigated the genotoxicity of this impurity by in silico and in vitro methods. We used Derek, a commercial structure-activity relationship software package, as an in silico tool. The results showed that there was a structural alert (quinoline) in this impurity. Then, the in vitro genotoxicity of descarboxyl levofloxacin was investigated by a modified Ames test and by a chromosomal aberration test, using Chinese hamster lung (CHL) cells. Both assays were conducted in the presence or absence of S-9 mix. The results showed that the test impurity was not mutagenic in the Ames test (31.25-500 MUg/plate). Whereas there was a statistically significant increase in the number of metaphase CHL cells with structural aberrations at the concentration of 1 mg/mL with S-9 mix, the aberrations rate was 7.5%. It did not significantly increase the number of structural aberration in CHL cells in the presence (at 250 and 500 MUg/mL) or absence of S-9 mix. Based on these assays, descarboxyl levofloxacin could be controlled as a nongenotoxic impurity. PMID- 24224726 TI - Evolution of influenza neuraminidase and the detection of antiviral resistant strains using mass trees. AB - A new approach employing mass trees is described and implemented which enables the evolution of influenza neuraminidase across all subtypes (N1-N9) in human and animal hosts to be monitored and charted without gene or protein sequencing. These mass trees are shown to be congruent with sequence based trees. Such trees can be built solely from the masses of the proteolytic peptide ions of viral proteins recorded by a mass spectrometer. They are shown to be able to correctly chart the evolutionary history of human pandemic influenza viruses, which originated in animal hosts, and can also resolve antiviral resistant from sensitive strains. Furthermore, experimental mass map data recorded for a circulating strain is correctly positioned onto a mass tree so as to quickly establish its evolutionary history and identify whether it is resistant or sensitive to the antiviral inhibitor oseltamivir. This new computational approach is expected to find wider application for evolutionary studies of organisms more generally. PMID- 24224727 TI - Magnetic superatoms in VLi(n) (n = 1-13) clusters: a first-principles prediction. AB - We demonstrated a first-principles investigation to search for magnetic superatoms in the vanadium-doped lithium clusters VLi(n) (n = 1-13). The stabilities of VLi(n) clusters were determined through geometrical and electronic optimizations. It is found that the growth pattern of VLi(n) in 3-space follows adding a Li atom capped on VLi(n-1) clusters. All doped clusters show larger relative binding energies compared with pure Li(n+1) partners and display tunable magnetic properties. When n = 8-13, the VLi(n) clusters adopt a cage-like structure with an endohedral V atom and are identified as superatoms with their magnetic moments successively decreasing from 5 to 0 MUB. The isolated VLi8 superatom is emphasized due to its robust magnetic moment as well as high structural and chemical stability analogue of a single Mn(2+) ion. Molecular orbitals analysis shows that VLi8 has an electronic configuration of 1S(2)1P(6)1D(5), exhibiting Hund's filling rule of maximizing the spin-like atoms. Electronic shell structures of 1S(2) and 1P(6) are virtually unchanged in Li9 cluster as the V atom substitutes for the embedded Li atom, indicating that the electron-shell-closing model is valid for explaining its structures and stabilities. The results show that the tailored magnetic building blocks for nanomaterials can be formed by seeding magnetic dopants into alkali metal cluster cages. PMID- 24224728 TI - Effectiveness of tadalafil 5 mg once daily in the treatment of men with lower urinary tract symptoms suggestive to benign prostatic hyperplasia with or without erectile dysfunction: results from naturalistic observational TadaLutsEd study. AB - INTRODUCTION: Naturalistic clinical trials provide data on the effectiveness of drugs in nonexperimental and everyday situations and are extremely helpful for decision-making purposes and for confirming experimental findings in clinical trials. No data have been published from naturalistic studies performed in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) with or without erectile dysfunction (ED) and treated with phosphodiesterase type 5 inhibitors. AIM: The aim of this study (TadaLutsEd Study) was to assess, in the context of medical practice, the effectiveness of tadalafil 5 mg once daily in patients with LUTS/BPH with or without erectile dysfunction. METHODS: The study was a 6-week uncontrolled, prospective, open label, multicentric, observational study. The patient population involved sexually active males aged >= 50 years, diagnosed with LUTS/BPH with or without concomitant ED, and treated with tadalafil 5 mg daily in accordance with standard urological practice. MAIN OUTCOME MEASURES: Effectiveness was assessed through the self-administered International Prostate Symptom Score (IPSS) questionnaire; quality of life was evaluated through the IPSS quality of life section (IPSS QoL). The patients were also evaluated with the International Index of Erectile Function (IIEF-5). Adverse events were recorded. Statistical analyses using paired data samples was applied (Wilcoxon signed-ranks test). RESULTS: Sixty-two patients (mean age 62.2 years) completed the treatment, of whom 85.5% showed improvement in their urinary symptoms. Pre- and post-treatment differences in the IPSS, IPSS-QoL, and IIEF-5 scores were statistically significant at 4.4, 1, and 5.4 points, respectively (P < 0.0001). Tadalafil was well tolerated, and adverse events were mild, with a discontinuation rate of 1.6%. CONCLUSION: According to study results, the use of tadalafil 5 mg once daily in a nonselected patient population with LUTS/BPH with or without ED led to improvements in terms of symptoms and quality of life and exhibited a safety profile similar to that obtained in controlled tadalafil clinical trials. PMID- 24224729 TI - Imidazopyridazine hepatitis C virus polymerase inhibitors. Structure-activity relationship studies and the discovery of a novel, traceless prodrug mechanism. AB - By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodrug mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented. PMID- 24224730 TI - Carbon nanotube core graphitic shell hybrid fibers. AB - A carbon nanotube yarn core graphitic shell hybrid fiber was fabricated via facile heat treatment of epoxy-based negative photoresist (SU-8) on carbon nanotube yarn. The effective encapsulation of carbon nanotube yarn in carbon fiber and a glassy carbon outer shell determines their physical properties. The higher electrical conductivity (than carbon fiber) of the carbon nanotube yarn overcomes the drawbacks of carbon fiber/glassy carbon, and the better properties (than carbon nanotubes) of the carbon fiber/glassy carbon make up for the lower thermal and mechanical properties of the carbon nanotube yarn via synergistic hybridization without any chemical doping and additional processes. PMID- 24224731 TI - Paediatric nurses' adherence to the double-checking process during medication administration in a children's hospital: an observational study. AB - AIM: To evaluate how closely double-checking policies are followed by nurses in paediatric areas and also to identify the types, frequency and rates of medication administration errors that occur despite the double-checking process. BACKGROUND: Double-checking by two nurses is an intervention used in many UK hospitals to prevent or reduce medication administration errors. There is, however, insufficient evidence to either support or refute the practice of double checking in terms of medication error risk reduction. DESIGN: Prospective observational study. METHODS: This was a prospective observational study of paediatric nurses' adherence to the double-checking process for medication administration from April-July 2012. RESULTS: Drug dose administration events (n = 2000) were observed. Independent drug dose calculation, rate of administering intravenous bolus drugs and labelling of flush syringes were the steps with lowest adherence rates. Drug dose calculation was only double-checked independently in 591 (30%) drug administrations. There was a statistically significant difference in nurses' adherence rate to the double-checking steps between weekdays and weekends in nine of the 15 evaluated steps. Medication administration errors (n = 191) or deviations from policy were observed, at a rate of 9.6% of drug administrations. These included 64 drug doses, which were left for parents to administer without nurse observation. CONCLUSION: There was variation between paediatric nurses' adherence to double-checking steps during medication administration. The most frequent type of administration errors or deviation from policy involved the medicine being given to the parents to administer to the child when the nurse was not present. PMID- 24224735 TI - Letter to the editor. PMID- 24224736 TI - Palmoplantar peeling secondary to sirolimus therapy. AB - Sirolimus (rapamycin) is an immunosuppressive agent commonly used in transplant recipients. Although sirolimus has less renal toxicity than calcineurin inhibitors, its use has been limited by its side effects. The most common cutaneous pathologies associated with sirolimus are inflammatory acneiform eruptions, lymphedema and aphthous ulcers. We present a novel cutaneous manifestation of sirolimus therapy that limited its use in at least one transplant recipient. Upon commencing sirolimus therapy, four solid organ transplant recipients developed tender, nonpruritic palmoplantar peeling within the first month of therapy. The peeling clinically resembled a mild form of hand foot syndrome, yet none of the patients had been treated with chemotherapeutics. Desquamation presented on the palms and soles with dry vesicles and minor peeling extending to the dorsal aspects of the hands and feet. Histologically, the lesions were noninflammatory; the epidermis showed subtle separation between keratinocytes, suggesting either spongiosis or a defect in intercellular adhesion. One patient opted to discontinue treatment because of the tenderness associated with the palmoplantar peeling, which resulted in complete resolution within 2 weeks. PMID- 24224737 TI - Suitability of a novel diet for a parasitic wasp, Cotesia plutellae. AB - The braconid Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae) is a major solitary, larval endoparasitoid of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae). The impact of dietary protein was investigated in the laboratory by comparing performance of C. plutellae on honey, which is commonly used to rear the parasitoid, to that on a novel diet made of honey and protein rich beebread. Cotesia plutellae was highly stimulated by honey and honey beebread, with a feeding response exceeding 95%, a level that is comparable with its responses to fructose, glucose, and sucrose. The ability of honey-beebread to support host-parasitoid colonies was also comparable with that of honey. However, parasitoids raised on honey-beebread suppressed diamondback moths in rearing cages 3 weeks before the honey-fed wasps. The development time of C. plutellae reared on honey with or without beebread showed no significant difference, but adult wasps lived longer on honey-beebread. Mean developmental periods from oviposition to pupation and from pupation to adult emergence were 8 and 6 days, respectively. Adult wasps raised on honey-beebread outlived their conspecifics that were raised on honey by at least 4 days. Honey-beebread showed potential as a good food for rearing C. plutellae in the laboratory, and its benefit in parasitoid production is discussed. PMID- 24224738 TI - Exercise reduced inflammation: but for how long after training? AB - BACKGROUND: Previous studies have reported that obese people with trisomy 21 suffer from low-grade systemic inflammation. A recent study has found that aerobic training reduced inflammation in obese women with Down syndrome. To the best of our knowledge, the study reported in this paper is the first to determine for how long these effects were maintained after completion of the programme. METHODS: Twenty premenopausal obese women (18-30 years old) with Down syndrome volunteered for this study. Eleven were randomly assigned to the intervention group and performed a 10-week aerobic training programme, 3 sessions per week, consisting of warming-up followed by treadmill exercise (30-40 min) at a work intensity of 55-65% of peak heart rate and a cooling-down period. The control group included 9, age, sex and BMI matched women with Down syndrome that did not perform any training programme. Fat mass percentage and distribution were measured. Plasma level of IL-6 and high-sensitive C-reactive protein (hs-CRP) were monitored. Time-course changes for these outcomes were assessed at pre- and post-intervention. Further, they were re-evaluated at 1, 3 and 6 months after completion of the programme. RESULTS: Three months after completion of the programme, plasma levels of IL-6 and hs-CRP were significantly increased. Up to 6 months later, both fat mass percentage and waist circumference (WC) were significantly increased. Furthermore, physical fitness was also impaired in the intervention group. No changes were observed in the control group. CONCLUSION: A 3-month detraining period significantly impaired chronic inflammation in obese women with DS. PMID- 24224739 TI - Nonvolatile organic thin film transistor memory devices based on hybrid nanocomposites of semiconducting polymers: gold nanoparticles. AB - We report the facile fabrication and characteristics of organic thin film transistor (OTFT)-based nonvolatile memory devices using the hybrid nanocomposites of semiconducting poly(9,9-dioctylfluorene-alt-bithiophene) (F8T2) and ligand-capped Au nanoparticles (NPs), thereby serving as a charge storage medium. Electrical bias sweep/excitation effectively modulates the current response of hybrid memory devices through the charge transfer between F8T2 channel and functionalized Au NPs trapping sites. The electrical performance of the hybrid memory devices can be effectively controlled though the loading concentrations (0-9 %) of Au NPs and organic thiolate ligands on Au NP surfaces with different carbon chain lengths (Au-L6, Au-L10, and Au-L18). The memory window induced by voltage sweep is considerably increased by the high content of Au NPs or short carbon chain on the ligand. The hybrid nanocomposite of F8T2:9% Au-L6 provides the OTFT memories with a memory window of ~41 V operated at +/- 30 V and memory ratio of ~1 * 10(3) maintained for 1 * 10(4) s. The experimental results suggest that the hybrid materials of the functionalized Au NPs in F8T2 matrix have the potential applications for low voltage-driven high performance nonvolatile memory devices. PMID- 24224740 TI - Assessing DSM-5 level of personality functioning from videotaped clinical interviews: a pilot study with untrained and clinically inexperienced students. AB - Several authors have raised the concern that the DSM-5 Level of Personality Functioning Scale (LPFS) is relatively complex and theory laden, and thus might put high requirements on raters. We addressed this concern by having 22 untrained and clinically inexperienced students assess the personality functioning of 10 female psychotherapy inpatients from videotaped clinical interviews, using a multi-item version of the LPFS. Individual raters' LPFS total scores showed acceptable interrater reliability, and were significantly associated with 2 distinct expert-rated measures of the severity of personality pathology. These findings suggest that, contrary to the previously mentioned concerns, successfully applying the LPFS to clinical cases might require neither extensive clinical experience nor training. PMID- 24224741 TI - Transport zonation limits coupled nitrification-denitrification in permeable sediments. AB - Measurement of biogeochemical processes in permeable sediments (including the hyporheic zone) is difficult because of complex multidimensional advective transport. This is especially the case for nitrogen cycling, which involves several coupled redox-sensitive reactions. To provide detailed insight into the coupling between ammonification, nitrification and denitrification in stationary sand ripples, we combined the diffusion equilibrium thin layer (DET) gel technique with a computational reactive transport biogeochemical model. The former approach provided high-resolution two-dimensional distributions of NO3(-) and (15)N-N2 gas. The measured two-dimensional profiles correlate with computational model simulations, showing a deep pool of N2 gas forming, and being advected to the surface below ripple peaks. Further isotope pairing calculations on these data indicate that coupled nitrification-denitrification is severely limited in permeable sediments because the flow and transport field limits interaction between oxic and anoxic pore water. The approach allowed for new detailed insight into subsurface denitrification zones in complex permeable sediments. PMID- 24224742 TI - Effects of ambroxol on Candida albicans growth and biofilm formation. AB - Typically, the onset of candidiasis is characterised by the appearance of a biofilm of Candida albicans, which is associated with several diseases including oral candidiasis in young and elderly people. The objective of this work was to investigate the in vitro fungicidal activity as well as the antibiofilm activity of ambroxol (AMB) against C. albicans growth. In the present investigation, the fungicidal activity of AMB was established using the cell viability 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also the minimum inhibitory concentration (MIC) of AMB required to inhibit the fungal growth was determined. Simultaneously, the antibiofilm activity of AMB was evaluated using fluorescence microscopy. The study revealed that 2 mg ml(-1) of AMB exhibited higher fungicidal activity than 3.3 mg ml(-1) of terbinafine, one of most common commercial antifungals. A MIC of 1 mg ml(-1) was determined for AMB to interfere with C. albicans growth. Furthermore, AMB was found to be effective in inhibiting the biofilm formation of C. albicans and exerted its fungicidal activity against the fungal cells interspersed in the preformed biofilm. The study suggests a potential role of the mucolytic agent, AMB, as an interesting therapeutic alternative in the treatment of oral candidiasis. PMID- 24224743 TI - Occlusion of the left coronary ostium by an infective endocarditis vegetation. PMID- 24224744 TI - Ascending aortic injuries following blunt trauma. AB - BACKGROUND: The diagnosis and the management of traumatic thoracic aortic injuries have undergone significant changes due to new technology and improved prehospital care. Most of the discussions have focused on descending aortic injuries. In this review, we discuss the recent management of ascending aortic injuries. METHODS: We found 5 cohort studies on traumatic aortic injuries and 11 case reports describing ascending aortic injuries between 1998 to the present through Medline research. RESULTS: Among case reports, 78.9% of cases were caused by motor vehicle accidents (MVA). 42.1% of patients underwent emergent open repair and the operative mortality was 12.5%. 36.8% underwent delayed repair. Associated injuries occurred in 84.2% of patients. Aortic valve injury was concurrent in 26.3% of patients. The incidence of ascending aortic injury ranged 1.9-20% in cohort studies. CONCLUSIONS: Traumatic injuries to the ascending aorta are relatively uncommon among survivors following blunt trauma. Aortography has been replaced by computed tomography and echocardiography as a diagnostic tool. Open repair, either emergent or delayed, remains the treatment of choice. PMID- 24224745 TI - Surgical outcome of reoperation due to left atrioventricular valve regurgitation after previous correction of complete atrioventricular septal defect. AB - OBJECTIVES: The aims of this study were to evaluate the early and late outcomes in patients undergoing reoperation due to left atrioventricular valve regurgitation (LAVVR) after initial complete repair (ICR) of complete atrioventricular septal defect (CAVSD). MATERIALS AND METHOD: Between January 1990 and April 2013, 45 consecutive patients underwent reoperation due to severe LAVVR. The mean age was 7.5 +/- 6.2 years. Associated LAVV malformations were found in 22 (49%) patients and associated cardiac malformations in 18 (40%). The mean follow-up was 6.8 +/- 2.6 years. RESULTS: LAVV repair was possible in all patients. There were two hospital deaths (4.5%). Ten patients (22%) required a second reoperation due to severe LAVVR at mean 7.5 +/- 8.4 months after the first reoperation. The actuarial overall survival and free-reoperation survival rates at one, three, and five years were 95.4%, 92.8%, and 92.8% and 89%, 80.5%, and 72%, respectively. Multivariate analysis revealed that the associated cardiac malformations, LAVV leaflet prolapse or detachment from the septal patch, associated LAVV malformations, and post-first correction LAVVR grade >= 2 were strong predictors for poor overall free-reoperation survival in patients undergoing reoperation due to LAVVR after ICR of various forms of ACVSD. CONCLUSIONS: Patients with severe LAVVR post-ICR of CAVSD may undergo reoperation with acceptable postoperative mortality and morbidity; however, they are at an increased risk for developing postoperative LAVVR and subsequent reoperation. PMID- 24224746 TI - Titanium dioxide nanoparticles relieve silk gland damage and increase cocooning of Bombyx mori under phoxim-induced toxicity. AB - Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. TiO2 nanoparticles have been demonstrated to increase pesticide resistance of Bombyx mori. While the toxicity of phoxim is well-documented, very limited information exists on the mechanisms of TiO2 nanoparticles improving the cocooning function of Bombyx mori following exposure to phoxim. The present study was, therefore, undertaken to determine whether TiO2 nanoparticles attenuate silk gland injury and elevate cocooning of B. mori following exposure to phoxim. The findings suggested that phoxim exposure resulted in severe damages of the silk gland structure and significantly decreased the cocooning in the silk gland of Bombyx mori. Furthermore, phoxim exposure significantly resulted in reductions of total protein concentrations and suppressed expressions of silk protein synthesis related genes, including Fib-L, Fib-H, P25, Ser-2, and Ser-3, in the silk gland. TiO2 nanoparticle pretreatment, however, could significantly relieve silk gland injury of Bombyx mori. Importantly, TiO2 nanoparticles could remarkably elevate cocooning and total protein contents and promote expressions of Fib-L, Fib-H, P25, Ser-2, and Ser-3 in the silk gland following exposure to phoxim. PMID- 24224747 TI - Cirrhosis but not neutropenia is associated with the development of infection in patients with chronic hepatitis C undergoing treatment with pegylated interferon alpha and ribavirin. AB - Peginterferon-alpha (PegIFNa) frequently causes neutropenia, mainly due to bone marrow suppression. The aim of this study was to explore factors that are associated with infections during antiviral treatment. We analysed data from 275 chronic hepatitis C (CHC) patients with compensated liver disease who underwent 318 courses of PegIFNa and ribavirin. Neutropenia was defined as neutrophils <1000 cells/MUL. Mean leucocytes count significantly decreased from baseline to treatment nadir (7081 +/- 2182 vs 3293 +/- 1331 cells/MUL, P < 0.001), while neutropenia was observed in 32% during treatment. Thirty-one infections were observed. The incidence rate for infection was assessed at 1.46 infections per 100 person-months of therapy. The hazard rate for infection did not correlate with the neutrophils' nadir or the decrease in white blood cells. In multivariate Cox's regression analysis, cirrhosis was the only factor that was significantly associated with the occurrence of infection. Our data show that the development of bacterial infections during treatment with PegIFNa and ribavirin in patients with compensated CHC is not associated with reduction or the nadir of white cells or neutrophil counts. Baseline cirrhosis is the only factor related with infection during treatment. The common practice of dose adjustment or discontinuation of interferon should be revised; careful assessment of liver damage before therapy and close monitoring during therapy are essential in all patients receiving interferon-based regimes, to minimize the detrimental consequences of infections. PMID- 24224748 TI - Collaborative partnership in age-friendly cities: two case studies from Quebec, Canada. AB - This article aims to explain the collaborative partnership conditions and factors that foster implementation effectiveness within the age-friendly cities (AFC) in Quebec (AFC-QC), Canada. Based on a community-building approach that emphasizes collaborative partnership, the AFC-QC implementation process is divided into three steps: (1) social diagnostic of older adults' needs; (2) an action plan based on a logic model; and (3) implementation through collaborations. AFC-QC promotes direct involvement of older adults and seniors' associations at each of the three steps of the implementation process, as well as other stakeholders in the community. Based on two contrasting case studies, this article illustrates the importance of collaborative partnership for the success of AFC implementation. Results show that stakeholders, agencies, and organizations are exposed to a new form of governance where coordination and collaborative partnership among members of the steering committee are essential. Furthermore, despite the importance of the senior associations' participation in the process, they encountered significant limits in the capacity of implementing age-friendly environments solely by themselves. In conclusion, we identify the main collaborative partnership conditions and factors in AFC-QC. PMID- 24224749 TI - Denver screening protocol for blunt cerebrovascular injury reduces the use of multi-detector computed tomography angiography. AB - BACKGROUND: Blunt cerebrovascular injury (BCVI) occurs in 0.2-2.7% of blunt trauma patients and has up to 30% mortality. Conventional screening does not recognize up to 20% of BCVI patients. To improve diagnosis of BCVI, both an expanded battery of screening criteria and a multi-detector computed tomography angiography (CTA) have been suggested. The aim of this study is to investigate whether the use of CTA restricted to the Denver protocol screen-positive patients would reduce the unnecessary use of CTA as a pre-emptive screening tool. METHODS: This is a registry-based study of blunt trauma patients admitted to Auckland City Hospital from 1998 to 2012. The diagnosis of BCVI was confirmed or excluded with CTA, magnetic resonance angiography and, if these imaging were non-conclusive, four-vessel digital subtraction angiography. RESULTS: Thirty (61%) BCVI and 19 (39%) non-BCVI patients met eligibility criteria. The Denver protocol applied to our cohort of patients had a sensitivity of 97% (95% confidence interval (CI): 83 100%) and a specificity of 42% (95% CI: 20-67%). With a prevalence of BCVI in blunt trauma patients of 0.2% and 2.7%, post-test odds of a screen-positive test were 0.03 (95% CI: 0.002-0.005) and 0.046 (95% CI: 0.314-0.068), respectively. CONCLUSIONS: Application of the CTA to the Denver protocol screen-positive trauma patients can decrease the use of CTA as a pre-emptive screening tool by 95-97% and reduces its hazards. PMID- 24224750 TI - Feasibility of a portable bihormonal closed-loop system to control glucose excursions at home under free-living conditions for 48 hours. AB - BACKGROUND: This study assessed the feasibility of a portable bihormonal closed loop system at home. SUBJECTS AND METHODS: Sixteen pump-treated patients with type 1 diabetes received 48 h of closed-loop therapy with a telemonitored insulin and glucagon-delivering closed-loop system and 48 h of patient-managed open-loop therapy. RESULTS: Owing to technical problems in five cases, only 11 patients could be analyzed. Whereas median (interquartile range) glucose levels were not significantly different during Day 1 of open-loop control (OL1) from closed-loop control (CL1) (8.27 [0.83] mmol/L vs. 8.84 [1.47] mmol/L; P=0.206), they were significantly lower during Day 2 of closed-loop control (CL2) versus open-loop control (OL2) (7.70 [2.29] mmol/L vs. 8.84 [0.87] mmol/L; P=0.027). Time spent in euglycemia (3.9-10 mmol/L) was comparable with 67.2% (38.5%) in OL1 versus 79.2% (16.9%) in CL1 (P=0.189) and 66.0% (29.8%) in OL2 versus 76.5% (23.9%) in CL2 (P=0.162). Time spent in hypoglycemia (<3.9 mmol/L) was comparable on Day 1 of control (OL1, 0.68% [8.68%]; CL1, 2.08% [7.61%]; P=0.593) but significantly higher during Day 2 of control (OL2, 0.00% [11.07%]; CL2, 2.8% [9.8%]; P=0.0172) (P=0.017). CONCLUSIONS: Bihormonal closed-loop control is feasible at home, with comparable time in euglycemia to open-loop control and significantly lower median glucose levels on Day 2 of control at the expense of more time in hypoglycemia, albeit still at a very low percentage of time. PMID- 24224751 TI - Improved diabetes screening using an extended predictive feature search. AB - BACKGROUND: Screening entire populations for diabetes is not cost-effective. Hence, an efficient screening process must select those people who are at high risk for diabetes. In this study, we investigated whether screening procedures could be improved using an extended predictive feature search. MATERIALS AND METHODS: In order to develop our model and identify persons with diabetes (prevalence) we used data from years of the National Health and Nutrition Examination Survey (2005-2010), which has not been explored for this purpose before. We calculated all combinations of predictors in order to identify the optimal subset, and we used a linear logistic classification model to predict diabetes. V-fold cross-validation was used for the process of including variables and for validating the final models. This new model was compared with two established models. RESULTS: In total, 5,398 participants were included in this study. Among these, 478 participants had unidentified diabetes. The established models had a receiver operating characteristics curve for the area under the curve (AUC) of 0.74 and 0.71 compared with an AUC of 0.78 for the new model, showing a significant difference (P<0.05). A proposed cutoff point for the established models yielded respective sensitivities/specificities of 63%/72% and 40%/72% compared with the new model, which had a sensitivity/specificity of 70%/72%. CONCLUSIONS: Our data indicate that simple healthcare and economic information such as ratio of family income to poverty can add value in deciding who is at risk of unknown diabetes by using extended investigations of predictor combinations. PMID- 24224752 TI - Hospital readmission and emergency department use based on prescribing patterns in patients with severely uncontrolled type 2 diabetes mellitus. AB - BACKGROUND: Patients with uncontrolled diabetes are more likely to be readmitted to the hospital. The study objective was to determine the risk of hospital admission or emergency department (ED) use in patients with severely uncontrolled type 2 diabetes mellitus based on whether their diabetes medication regimen was intensified at discharge. SUBJECTS AND METHODS: A retrospective cohort study of patients admitted to the medicine services at an academic medical center was conducted during a 9-month period. Medical records were reviewed to identify patients with type 2 diabetes mellitus and hemoglobin A1c >10% who were admitted for more than 24 h. Primary exclusion criteria included pregnancy, age >65 or <18 years, life expectancy of <12 months, hypoglycemia at admission, and new diagnosis of type 2 diabetes. Admission medication lists for patients were compared with discharge medications to determine whether the diabetes regimen was intensified. Patients whose regimen was intensified were then compared with patients whose regimen was not intensified for admissions and ED visits within 3 months after discharge. The primary end point was 90-day all-cause hospital and ED visits. RESULTS: Patients who had their regimens intensified had significantly fewer average all-cause hospital and ED visits at 90 days (0.41 vs. 0.85; P=0.044). Statistical differences were also found in 30-day all-cause visits, readmissions within 90 days, and hospital-free time. CONCLUSIONS: Patients whose home diabetes regimen was intensified at discharge were less likely to return to the hospital within 90 days compared with patients whose regimen was not intensified. PMID- 24224753 TI - Construction of spiro-fused 2-oxindole/alpha-methylene- gamma-butyrolactone systems with extremely high enantioselectivity via indium-catalyzed amide allylation of N-methyl isatin. AB - A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/alpha-methylene-gamma-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms. PMID- 24224755 TI - Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure. AB - BACKGROUND AND AIMS: Acute liver failure (ALF) is a critical illness with high mortality. Plasma diafiltration (PDF) is a blood purification therapy that is useful for ALF patients, but it is difficult to use when those patients have multiple organ failure or unstable hemodynamics. In these patients, symptoms are also likely to exacerbate immediately after PDF therapy. We developed continuous PDF (CPDF) as a new concept in PDF therapy, and assessed its efficacy and safety in ALF patients. METHODS: Ten ALF patients (gender: M/F 6/4, Age: 47 +/- 14) were employed CPDF therapy. The primary outcomes were altered liver function, measured by the model for end-stage liver disease (MELD) score, and total bilirubin and prothrombin time international normalized ratios (PT-INR), 5 days after CPDF therapy. Secondary outcomes included sequential organ failure assessment (SOFA) scores, 5 days after CPDF therapy, and the survival rate 14 days after this therapy. RESULTS: The MELD score (34.5-28.0; P = 0.005), total bilirubin (10.9 7.25 mg/dL; P = 0.048), PT-INR (1.89-1.31; P = 0.084), and SOFA score (10.0-7.5; P < 0.039) were improved 5 days after CPDF therapy. Nine patients were alive, and one patient died because of acute pancreatitis, complicated by ALF. There were no major adverse events related to this therapy under hemodynamic stability. CONCLUSION: In the present study, CPDF therapy safely supported liver function and generally improved the condition of critically ill patients with ALF. PMID- 24224756 TI - Comparison of invasive and oscillometric blood pressure measurement techniques in anesthetized sheep, goats, and cattle. AB - OBJECTIVE: To determine the level of agreement between an oscillometric (O-NIBP) and an invasive method (IBP) of monitoring arterial blood pressure (ABP) in anesthetized sheep, goats, and cattle. STUDY DESIGN: Prospective clinical study. ANIMALS: Twenty sheep and goats, 20 cattle weighing < 150 kg body weight, and 20 cattle weighing 150 kg body weight. METHODS: Animals were anesthetized and systolic ABP (SABP), mean ABP (MABP), and diastolic ABP (DABP) were measured using IBP and O-NIBP. Differences between IBP and O-NIBP, and 95% limits of agreement (LOA) between SABP, MABP, and DABP values were assessed by the Bland Altman method. RESULTS: Mean difference +/- standard deviation (range) between SABP, DABP, and MABP measurements in sheep and goats was 0 +/- 16 (-57 to 38) mmHg, 13 +/- 16 (-37 to 70) mmHg, and 8 +/- 13 (-34 to 54) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in small cattle was 0 +/- 19 (-37 to 37) mmHg, 6 +/- 18 (-77 to 48) mmHg, and 4 +/- 16 (-73 to 48) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in large cattle was -18 +/- 32 (-107 to 71) mmHg, 7 +/- 29 (-112 to 63) mmHg, and -5 +/- 28 (-110 to 60) mmHg, respectively. The 95% LOAs for SABP, DABP, and MABP were -31 to +31, -19 to +44, and -19 to +34 mmHg, respectively in sheep and goats; were -37 to +37, -19 to +44, and -19 to +34 mmHg, respectively in small cattle; and were -81 to +45, -50 to +63, and -59 to +50 mmHg, respectively in large cattle. CONCLUSIONS: Agreement was poor between O-NIBP and IBP monitoring techniques. CLINICAL RELEVANCE: Arterial BP should be monitored in anesthetized sheep, goats, and cattle using IBP. PMID- 24224758 TI - Improved multidimensional semiclassical tunneling theory. AB - We show that the analytic multidimensional semiclassical tunneling formula of Miller et al. [Miller, W. H.; Hernandez, R.; Handy, N. C.; Jayatilaka, D.; Willets, A. Chem. Phys. Lett. 1990, 172, 62] is qualitatively incorrect for deep tunneling at energies well below the top of the barrier. The origin of this deficiency is that the formula uses an effective barrier weakly related to the true energetics but correctly adjusted to reproduce the harmonic description and anharmonic corrections of the reaction path at the saddle point as determined by second order vibrational perturbation theory. We present an analytic improved semiclassical formula that correctly includes energetic information and allows a qualitatively correct representation of deep tunneling. This is done by constructing a three segment composite Eckart potential that is continuous everywhere in both value and derivative. This composite potential has an analytic barrier penetration integral from which the semiclassical action can be derived and then used to define the semiclassical tunneling probability. The middle segment of the composite potential by itself is superior to the original formula of Miller et al. because it incorporates the asymmetry of the reaction barrier produced by the known reaction exoergicity. Comparison of the semiclassical and exact quantum tunneling probability for the pure Eckart potential suggests a simple threshold multiplicative factor to the improved formula to account for quantum effects very near threshold not represented by semiclassical theory. The deep tunneling limitations of the original formula are echoed in semiclassical high-energy descriptions of bound vibrational states perpendicular to the reaction path at the saddle point. However, typically ab initio energetic information is not available to correct it. The Supporting Information contains a Fortran code, test input, and test output that implements the improved semiclassical tunneling formula. PMID- 24224757 TI - Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation. AB - Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate inhibitor of influenza A virus (IAV) in the lung. Interactions of SP-D with highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV envelope protein and critical virulence factor, promote viral aggregation and neutralization through as yet unknown molecular mechanisms. Two truncated human SP-D forms, wild-type (WT) and double mutant D325A+R343V, representing neck and carbohydrate recognition domains are compared in this study. Whereas both WT and D325A+R343V bind to isolated glycosylated HA, WT does not inhibit IAV in neutralization assays; in contrast, D325A+R343V neutralization compares well with that of full-length native SP-D. To elucidate the mechanism for these biochemical observations, we have determined crystal structures of D325A+R343V in the presence and absence of a viral nonamannoside (Man9). On the basis of the D325A+R343V-Man9 structure and other crystallographic data, models of complexes between HA and WT or D325A+R343V were produced and subjected to molecular dynamics. Simulations reveal that whereas WT and D325A+R343V both block the sialic acid receptor site of HA, the D325A+R343V complex is more stable, with stronger binding caused by additional hydrogen bonds and hydrophobic interactions with HA residues. Furthermore, the blocking mechanism of HA differs for WT and D325A+R343V because of alternate glycan binding modes. The combined results suggest a mechanism through which the mode of SP-D-HA interaction could significantly influence viral aggregation and neutralization. These studies provide the first atomic-level molecular view of an innate host defense lectin inhibiting its viral glycoprotein target. PMID- 24224759 TI - Outcome of kidney transplantations performed with preformed donor-specific antibodies of unknown etiology. AB - The detection of preformed donor-specific alloantibodies (DSA) with multiplex bead arrays has led to the common observation that individuals without a history of pregnancy, transfusion or transplantation can have circulating anti-HLA antibodies of unknown etiology. We retrospectively analyzed the risk of antibody mediated rejection (AMR) and graft outcome in 41 kidney transplant recipients with DSA of unknown etiology (DSA cause-unk) at the time of transplantation. Twenty-one patients received a posttransplantation desensitization protocol, and 20 received standard immunosuppressive therapy. The mean number of DSA was 1.4 +/ 0.8, ranging from 1 to 5. Complement-dependent cytotoxicity crossmatches were negative for all the patients. Flow cytometry crossmatches were positive in 47.6% of cases. The incidence of acute AMR was 14.6% at 1 year, regardless of the immunosuppressive regimen. No patients experienced graft loss following AMR. At month 12, across the entire population of patients with DSA cause-unk, the outcomes were favorable: the measured glomerular filtration rate was 63.8 +/- 16.4 mL/min/1.73 m(2), the screening biopsies showed low frequencies of microvascular inflammation and no transplant glomerulopathy, and graft and patient survival were 100%. In conclusion, patients with DSA cause-unk are able to mount AMR but have favorable 1-year outcomes. PMID- 24224760 TI - Constructing identities in the media: newspaper coverage analysis of a major UK Clostridium difficile outbreak. AB - AIM: To examine how a major Clostridium difficile outbreak in the UK was represented in the media. BACKGROUND: Clostridium difficile is a serious health care-associated infection with significant global prevalence. As major outbreaks have continued to occur worldwide over the last few decades, it has also resulted in increasing media coverage. Newspaper journalists are, however, frequently criticized for sensationalized and inaccurate reporting and alarming the public. Despite such criticisms, nothing is known about how the media frame Clostridium difficile related coverage. DESIGN: Qualitative interpretive descriptive study. METHOD: An interpretive analysis of newspaper articles from the national press that reported about the outbreak from the first day of coverage over 3 weeks (12 June-3 July 2008). FINDINGS: Twenty-eight newspaper articles were included in the study from tabloids, broadsheets, a regional and a Sunday newspaper. Monster and war metaphors were frequently adopted to portray the severity of Clostridium difficile and the impact it can have on patient safety. In addition, the positioning of the affected patients, their families, healthcare professionals and the Government produced representations of victims, villains and heroes. This subsequently evoked notions of vulnerability, blame and conflict. CONCLUSION: The media are and will remain critical convectors of public information and, as such, are hugely influential in risk perceptions and responses. Rather than simply dismissing media coverage, further understanding around how such stories in specific contexts are constructed and represented is needed so that it can help inform future communication and management strategies. PMID- 24224761 TI - The Female Sexual Function Index (FSFI): linguistic validation of the Italian version. AB - INTRODUCTION: Although several new measurements for female sexual dysfunction (FSD) have recently been developed, the Female Sexual Function Index (FSFI) remains the gold standard for screening and one of the most widely used questionnaires. The Italian translation of the FSFI has been used in several studies conducted in Italy, but a linguistic validation of the Italian version does not exist. AIM: The aim of this study was to perform a linguistic validation of the Italian version of the FSFI. METHODS: A multicenter cross-sectional study conducted in 14 urological and gynecological clinics, uniformly distributed over Italian territory. We performed all steps necessary to determine the reliability and the test-retest reliability of the Italian version of the FSFI. The study population was a convenience sample of 409 Italian women. MAIN OUTCOME MEASURES: The reliability of the questionnaire was calculated using Cronbach's alpha, which was considered weak, moderate, or high if its value was found less than 0.6, between 0.6 and 0.8, or equal to or greater than 0.8, respectively. The test retest reliability was assessed for all women in the sample by calculating Pearson's concordance correlation coefficient for each domain and for the total score, both at baseline and after 15 days (r range between -1.00 to +1.00, where +1.00 indicates the strongest positive association). RESULTS: Cronbach's alpha coefficients for total and domain score were sufficiently high, ranging from 0.92 to 0.97 for the total sample. The test-retest procedure revealed that the concordance correlation coefficient was very high both for FSFI-I total score (Pearson's P = 0.93) and for each domain (Pearson's P always >0.92). CONCLUSION: For the first time in the literature, our study has produced a validated and reliable Italian version of the FSFI questionnaire. Consequently, the Italian FSFI can be used as a reliable tool for preliminary screening for female sexual dysfunction for Italian women. PMID- 24224762 TI - Spikar speaks to spines and nuclei. PMID- 24224763 TI - Removal of human ether-a-go-go related gene (hERG) K+ channel affinity through rigidity: a case of clofilium analogues. AB - Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-a-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we designed and synthesized a series of 40 derivatives of clofilium, a class III antiarrhythmic agent. These were evaluated in radioligand binding and patch-clamp assays to establish structure-affinity relationships (SAR) for this potassium channel. Efforts were especially focused on studying the influence of the structural rigidity and the nature of the linkers composing the clofilium scaffold. It was shown that introducing triple bonds and oxygen atoms in the n butyl linker of the molecule greatly reduced affinity without significantly modifying the pKa of the essential basic nitrogen. These findings could prove useful in the first stages of drug discovery as a systematic way of reducing the risk of hERG K(+) channel blockade-induced cardiotoxicity. PMID- 24224765 TI - Phosphorus molecules on Ge(001): a playground for controlled n-doping of germanium at high densities. AB - The achievement of controlled high n-type doping in Ge will enable the fabrication of a number of innovative nanoelectronic and photonic devices. In this work, we present a combined scanning tunneling microscopy, secondary ions mass spectrometry, and magnetotransport study to understand the atomistic doping process of Ge by P2 molecules. Harnessing the one-dimer footprint of P2 molecules on the Ge(001) surface, we achieved the incorporation of a full P monolayer in Ge using a relatively low process temperature. The consequent formation of P-P dimers, however, limits electrical activation above a critical donor density corresponding to P-P spacing of less than a single dimer row. With this insight, tuning of doping parameters allows us to repeatedly stack such 2D P layers to achieve 3D electron densities up to ~2 * 10(20) cm(-3). PMID- 24224764 TI - Genetic and morphological approaches distinguish the three sibling species of the Anisakis simplex species complex, with a species designation as Anisakis berlandi n. sp. for A. simplex sp. C (Nematoda: Anisakidae). AB - Numerous specimens of the 3 sibling species of the Anisakis simplex species complex (A. pegreffii, A. simplex (senso stricto)), and A. simplex sp. C) recovered from cetacean species stranded within the known geographical ranges of these nematodes were studied morphologically and genetically. The genetic characterization was performed on diagnostic allozymes and sequences analysis of nuclear (internal transcribed spacer [ITS] of ribosomal [r]DNA) and mitochondrial (mitochondrial [mt]DNA cox2 and rrnS) genes. These markers showed (1) the occurrence of sympatry of the 2 sibling species A. pegreffii and A. simplex sp. C in the same individual host, the pilot whale, Globicephala melas Traill, from New Zealand waters; (2) the identification of specimens of A. pegreffii in the striped dolphin, Stenella coeruleoalba (Meyen), from the Mediterranean Sea; and (3) the presence of A. simplex (s.s.) in the pilot whale and the minke whale, Balaenoptera acutorostrata Lacepede, from the northeastern Atlantic waters. No F1 hybrids were detected among the 3 species using the nuclear markers. The phylogenetic inference, obtained by maximum parsimony (MP) analysis of separate nuclear (ITS rDNA region), combined mitochondrial (mtDNA cox2 and rrnS) sequences datasets, and by concatenated analysis obtained at both MP and Bayesian inference (BI) of the sequences datasets at the 3 studied genes, resulted in a similar topology. They were congruent in depicting the existence of the 3 species as distinct phylogenetic lineages, and the tree topologies support the finding that A. simplex (s.s.), A. pegreffii, and A. berlandi n. sp. (= A. simplex sp. C) represent a monophyletic group. The morphological and morphometric analyses revealed the presence of morphological features that differed among the 3 biological species. Morphological analysis using principal component analysis, and Procrustes analysis, combining morphological and genetic datasets, showed the specimens clustering into 3 well-defined groups. Nomenclatural designation and formal description are given for A. simplex species C: the name Anisakis berlandi n. sp. is proposed. Key morphological diagnostic traits are as follows between A. berlandi n. sp. and A. simplex (s.s.): ventriculus length, tail shape, tail length/total body length ratio, and left spicule length/total body length ratio; between A. berlandi n. sp. and A. pegreffii: ventriculus length and plectane 1 width/plectane 3 width ratio; and between A. simplex (s.s.) and A. pegreffii: ventriculus length, left and right spicule length/total body length ratios, and tail length/total body length ratio. Ecological data pertaining to the geographical ranges and host distribution of the 3 species are updated. PMID- 24224766 TI - An enzymatic chemical amplifier based on mechanized nanoparticles. AB - A chemical amplifier was constructed based on enzyme-encapsulated mesoporous silica nanoparticles. By employing a supramolecular nanogate assembly that is capable of controlling the access to the encapsulated enzyme, selectivity toward substrate sizes is enabled. When an analyte molecule actuates the mechanical nanogate and exposes the enzymes, a catalytic production of fluorescent molecules is initiated. This study demonstrates a new concept of self-amplification of a chemical sensing process and can potentially increase the detection sensitivity. PMID- 24224767 TI - Concentrations, fluxes, and residence time of PBDEs across the tropical Atlantic Ocean. AB - Little is known about the fate of polybrominated diphenylethers (PBDEs) across the Oceans. Air and water were sampled using both active and passive polyethylene samplers on an east-west transect across the tropical Atlantic Ocean in 2009 and analyzed for PBDEs. Typical particle-bound concentrations of PBDEs in the surface water were low, at <1 pg L(-1). Truly dissolved concentrations from passive samplers were ~0.5 pg L(-1) for BDE 47 and around 0.1 pg L(-1) for BDEs 28, 99, and 100 (results from active samples were compromised). In the atmosphere, particle-bound BDE 209 dominated overall concentrations (median 1.2 pg m(-3)), followed by BDE 99 (0.13 pg m(-3)). Gas-phase concentrations based on passive samplers were 1-8 pg m(-3) for BDE 47 and <= 4 pg m(-3) for BDE 99. Net air-water exchange gradients strongly favored gas-phase deposition of PBDEs into the water. Net gas-phase deposition fluxes ranged from tens of pg m(-2) day(-1) for BDEs 28 and 85 to around 1 ng m(-2) day(-1) for BDE 47, 99, and 209. Settling fluxes of particle-bound PBDEs in the atmosphere and surface water were around 50 pg m(-2) day(-1) for BDE 47 and <10 pg m(-2) day(-1) for the other congeners. PMID- 24224768 TI - Practice leadership and active support in residential services for people with intellectual disabilities: an exploratory study. AB - BACKGROUND: We hypothesised that a key factor determining the quality of active support was 'practice leadership' - provided by the first-line manager to focus staff attention and develop staff skills in providing direct support to enable people with intellectual disabilities to have a good quality of life. This exploratory study focused on what levels of practice leadership were found and its role in explaining variation in active support. METHOD: Relevant aspects of management, including practice leadership, were assessed by questionnaires administered to staff in residential settings alongside observational measures of active support and resident engagement in meaningful activity. Relationships between these variables were explored using regression and post hoc group comparisons. RESULTS: There was wide variation, with average levels of practice leadership being low, though improving over the period studied. Practice leadership had a significant impact on active support, but was fully mediated by the effect of quality of management. When the quality of management was higher better practice leadership did produce a significant difference in active support. However, higher quality of management on its own did not produce better active support. CONCLUSIONS: A number of limitations are acknowledged and further research is required. Practice leadership appears to be an important factor in enabling staff to provide active support but as part of generally good management. Given the rather low levels found, attention needs to be given to the training, career development and support of practice leaders and also to how to protect their time from their many other responsibilities. PMID- 24224769 TI - An essential esterase (BroH) for the mineralization of bromoxynil octanoate by a natural consortium of Sphingopyxis sp. strain OB-3 and Comamonas sp. strain 7D-2. AB - A natural consortium of two bacterial strains ( Sphingopyxis sp. OB-3 and Comamonas sp. 7D-2) was capable of utilizing bromoxynil octanoate as the sole source of carbon for its growth. Strain OB-3 was able to convert bromoxynil octanoate to bromoxynil but could not use the eight-carbon side chain as its sole carbon source. Strain 7D-2 could not degrade bromoxynil octanoate, although it was able to mineralize bromoxynil. An esterase (BroH) that is involved in the conversion of bromoxynil octanoate into bromoxynil and is essential for the mineralization of bromoxynil octanoate by the consortium was isolated from strain OB-3 and molecularly characterized. BroH encodes 304 amino acids and resembles alpha/beta-hydrolase fold proteins. Recombinant BroH was overexpressed in Escherichia coli BL21 (DE3) and purified by Ni-NTA affinity chromatography. BroH was able to transform p-nitrophenyl esters (C2-C14) and showed the highest activity toward p-nitrophenyl caproate (C6) on the basis of the catalytic efficiency value (Vmax/Km). Additionally, BroH activity decreased when the aliphatic chain length increased. The optimal temperature and pH for BroH activity was found to be 35 degrees C and 7.5, respectively. On the basis of a phylogenetic analysis, BroH belongs to subfamily V of bacterial lipolytic enzymes. PMID- 24224770 TI - To spare or not to spare...? The aortic valve in scleroderma and aortic root aneurysm. AB - Acute valve-sparing procedures are effective in the treatment of aortic root dilation when there is no valve pathology. In this review, we discuss the role of aortic valve-sparing procedures in the presence of connective tissue disorders such as scleroderma. PMID- 24224771 TI - DNA methylation score is predictive of myeloma cell sensitivity to 5-azacitidine. PMID- 24224772 TI - Safety and efficacy of probiotics in Candida colonisation and infection: where do they stand. PMID- 24224773 TI - Electrolyte-gated, high mobility inorganic oxide transistors from printed metal halides. AB - Inkjet printed and low voltage (<=1 V) driven field-effect transistors (FETs) are prepared from precursor-made In2O3 as the transistor channel and a composite solid polymer electrolyte (CSPE) as the gate dielectric. Printed halide precursors are annealed at different temperatures (300-500 degrees C); however, the devices that are heated to 400 degrees C demonstrate the best electrical performance including field-effect mobility as high as 126 cm(2) V(-1) s(-1) and subthreshold slope (68 mV/dec) close to the theoretical limit. These outstanding device characteristics in combination with ease of fabrication, moderate annealing temperatures and low voltage operation comprise an attractive set of parameters for battery compatible and portable electronics. PMID- 24224774 TI - Desired social distance from people who have hepatitis C virus: an exploration among staff in health care, dentistry, drug treatment, and tattoo/body piercing. AB - Staff who work in facilities such as health care, dentistry, drug treatment, and tattoo/body piercing are likely to encounter persons with hepatitis C virus (HCV) and be privy to their HCV status. The purpose of this paper is to assess staff comfort with varying levels of intimacy (i.e., social distance) with people who have HCV. We examine how previous contact with persons with HCV and knowledge of HCV including HCV specific training affect desire for social distance. Data are from a 2007 sample of 82 individuals working in health care, dentistry, drug treatment, or tattoo/body-piercing studios located in the Pacific Northwest region of the United States. Multivariate analyses indicate that staff desire social distance from persons with HCV, but contact of certain types reduce desire for social distance. We discuss how the findings have implications for people employed in these fields, as they point to the need to dispel myths and reduce fear among staff working in facilities that may serve persons with HCV. PMID- 24224775 TI - The aquatic communities inhabiting internodes of two sympatric bamboos in Argentinean subtropical forest. AB - In order to determine if phytotelmata in sympatric bamboos of the genus Guadua might be colonized by different types of arthropods and contain communities of different complexities, the following objectives were formulated: (1) to analyze the structure and species richness of the aquatic macroinvertebrate communities, (2) to comparatively analyze co-occurrences; and (3) to identify the main predators. Field studies were conducted in a subtropical forest in Argentina, where 80 water-filled bamboo internodes of Guadua chacoensis (Rojas Acosta) Londono and Peterson (Poales: Poaceae) and G. trinii (Nees) Nees and Rupr. were sampled. Morphological measurements indicated that G. chacoensis held more fluid than G. trinii. The communities differed between Guadua species, but many macroinvertebrate species used both bamboo species. The phytotelmata were mainly colonized by Diptera of the families Culicidae and Ceratopogonidae. PMID- 24224776 TI - Does the Village model help to foster age-friendly communities? AB - This article explores the potential role of the Village model, a social initiative that emphasizes member involvement and service access, in helping communities to become more age-friendly. A survey of 86.3% of operational Villages examined activities designed to help members access a variety of supports and services consistent with the World Health Organization's (WHO) Global Network of Age-Friendly Cities and Communities program model, as well as other potential contributions to community age friendliness. Analysis revealed that 85.5% of Villages provided assistance with at least six of the eight WHO domains, but only 10.1% implemented features of all eight; more than one-third were engaged in direct or indirect efforts to improve community physical or social infrastructures or improve community attitudes toward older persons. These findings suggest that Villages and other social organizations may have untapped potential for enhancing their members' ability to age in place consistent with the goals of age-friendly initiatives while also promoting constructive changes in the overall community. PMID- 24224777 TI - Switching from branded to generic inhaled medications: potential impact on asthma and COPD. AB - Pressure on healthcare budgets is increasing, while at the same time patent protection for many branded inhaled medications has expired, leading to the development and growing availability of generic inhaled medicines. Generic inhaled drugs are therapeutically equivalent to original branded options but may differ in their formulation and inhalation device. This new situation raises questions about the potential impact of switching from branded to generic drug/inhaler combination products in patients with asthma or COPD, with or without their consent, in countries where this is permitted. Inhalation devices, particularly dry powder inhalers, vary markedly in their design, method of operation and drug delivery to the lungs. Current guidelines stress the importance of training patients how to use their inhalers but offer little or no guidance on how this should be achieved. Non-adherence to therapy and incorrect inhaler usage are recognised as major factors in poorly or uncontrolled asthma and COPD and switching patients to a different inhaler device may exacerbate these problems, particularly in patients who disagree to switch. Where switching is permitted or mandatory, adequate patient instruction and follow-up monitoring should be provided routinely. PMID- 24224778 TI - Cystogram use and outcomes in colorectal surgery involving bladder repair: a clinical audit. AB - BACKGROUND: The role of routine cystograms after bladder repair during colorectal surgery is unclear so we aimed to evaluate this in our department. METHODS: We conducted a retrospective audit of colorectal surgical patients who had an operation and subsequent cystogram between 2006 and 2011 at the Norfolk and Norwich University Hospital. Data on patient characteristics, operative procedures and findings, and cystogram results were collected from electronic discharge summaries, operative notes and radiological records. RESULTS: A total of 59 operations were included and 92% had documented bladder involvement. The most common indications for surgery were diverticular disease (49%) and neoplastic disease (39%). Operations evaluated included high anterior resection, anterior resection, Hartmann's procedures and sigmoid colectomy. Although all patients had at least one post-operative cystogram, only 46% of cases had instructions documented in the operative note for a cystogram to be arranged. Out of the 59 operations, 4 (7%) had cystograms that showed a leak. Repeat cystography in these cases showed no leak or smaller leak and no additional procedures were required. Two of the leaks occurred in cases that had extensive bladder involvement or bladder wall sepsis, and two occurred in cases where the operative findings revealed less major bladder pathology. CONCLUSIONS: Our results suggest that majority of cystograms are negative. More studies are needed to evaluate if selective use of cystogram should be performed to reduce unnecessary the risks associated with radiation exposure and contrast exposure. PMID- 24224779 TI - Comparison of long-term effectiveness and complications of radiofrequency ablation with hepatectomy for small hepatocellular carcinoma. AB - BACKGROUND AND AIM: To determine and compare the adverse events and long-term effectiveness for patients with small hepatocellular carcinoma (HCC) (<= 3 cm) treated by percutaneous radiofrequency ablation (RFA) or hepatectomy. METHODS: Small HCC from 120 patients were randomized into either percutaneous RFA therapy or hepatectomy group, and the effectiveness and complications of two treatment modalities were analyzed. The complications of post-RFA or hepatectomy, the complete treatment rate, treatment-related mortality, and disease-free and overall survival rate were followed up and conducted. RESULTS: In patients with small HCC, complete remission rates were achieved in 95% and 96.7% in the percutaneus RFA and hepatectomy groups, respectively (P > 0.05). Hepatic function at day-7 status post-treatment, including albumin and bilirubin levels, were significantly worse in the hepatectomy group (P < 0.01). Compared with the RFA group, the incidence of postoperative complications (27.5% vs 5.0%) and hospital stay (11.8 +/- 3.1 vs 4.3 +/- 1.5) were significantly higher in the hepatectomy group (P < 0.01). After a mean follow-up of 40 months, 22 patients (36.6%) in the RFA group and 21 patients (35.0%) in the hepatectomy group developed a recurrence (P > 0.05). There was no significant difference of the disease-free and overall survival rates at 1, 2, and 3 years between the RFA group and the surgical hepatectomy group (P = 0.443 and P = 0.207, respectively). CONCLUSIONS: In patients with small HCC, percutaneous RFA showed similar local control and long term survival compared with hepatectomy. Importantly, percutaneous RFA are accompanied with a lower complication rate and shorter hospital stay day. PMID- 24224781 TI - Predictors of early treatment discontinuation in a cohort of patients treated with boceprevir-based therapy for hepatitis C infection. AB - In this real-world cohort, 49% of patients stopped boceprevir-based hepatitis C therapy early, with only 20% stopping due to treatment futility. Having more comorbidities was significantly associated with early discontinuation. Tolerability of boceprevir-based regimens may be substantially worse than reported in clinical trials, particularly for patients with comorbidities. PMID- 24224782 TI - The role of IL-6 on apical periodontitis: a systematic review. AB - The aim of this review was to examine current knowledge of the role of interleukin-6 (IL-6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro-inflammatory cytokine. It also looked at whether IL-6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL-6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL-6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL-6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL-6 is present in AP and that osteoblasts can produce IL-6 in vivo. On the other hand, two studies using IL-6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL-6's role as an anti-inflammatory cytokine. In human studies (n = 7), IL-6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL-6 may play a pro-inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL-6 is not present, other cytokines such as IL-1 and TNF-alpha induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process. PMID- 24224785 TI - On the ethics of using non-certified health 'remedies' in resource poor contexts. PMID- 24224786 TI - Hemoglobin Bohr effects: atomic origin of the histidine residue contributions. AB - The Bohr effect in hemoglobin, which refers to the dependence of the oxygen affinity on the pH, plays an important role in its cooperativity and physiological function. The dominant contribution to the Bohr effect arises from the difference in the pKa values of His residues of the unliganded (deoxy) and liganded (carbonmonoxy) structures. Using recent high resolution structures, the residue pKa values corresponding to the two structures are calculated. The method is based on determining the electrostatic interactions between residues in the protein, relative to those of the residue in solution, by use of the linearized finite difference Poisson-Boltzmann equation and Monte Carlo sampling of protonation states. Given that good agreement is obtained with the available experimental values for the contribution of His residues in HbA to the Bohr effect, the calculated results are used to determine the atomic origin of the pKa shift between deoxy and carbonmonoxy HbA. The contributions to the pKa shift calculated by means of the linear response approximation show that the salt bridge involving His146 plays an important role in the alkaline Bohr effect, as suggested by Perutz but that other interactions are significant as well. A corresponding analysis is made for the contribution of His143 to the acid Bohr effect for which there is no proposed explanation. The method used is summarized and the program by which it is implemented is described in the Appendix . PMID- 24224787 TI - Effectiveness of a peer-led self-management programme for people with schizophrenia: protocol for a randomized controlled trial. AB - AIM: To determine the effectiveness of a peer-led self-management programme for people with schizophrenia in reducing psychotic symptom severity, hospital readmission and psychiatric consultation and in enhancing cognition, empowerment, functioning level, medication adherence, perceived recovery, quality of life and social support. BACKGROUND: Several self-management programmes have been developed to empower patients with severe mental illness in achieving recovery. Research suggests that peer-led self-management programmes have positive effects on patient recovery. However, the existing evidence is inconclusive, due to a lack of credible evidence and long-term follow-up evaluations. DESIGN: A stratified randomized controlled trial will be conducted at six community mental health rehabilitation centres METHODS: A sample of 242 adults with schizophrenia will be recruited. A peer-led self-management programme, comprising six 2-hour sessions, will be implemented in the intervention group and a standard rehabilitation programme in the control group. Outcomes will be measured at baseline, postintervention and at the 6- and 12-month follow-ups. The measures will include cognition, empowerment, functioning level, medication adherence, perceived recovery, quality of life, social support, symptom severity, hospital readmission and psychiatric consultation. A mixed effects model will be used to analyse the results. Semi-structured interviews will be conducted to explore the peer-trainers' and participants' perspectives on the programme. Research Ethics Committee approval was obtained in December 2011 and funding was obtained in January 2012. CONCLUSION: This study will provide evidence on the effectiveness of a peer-led self-management programme for patient recovery. It will identify a clinically useful and potentially effective intervention that incorporates empowerment concept. PMID- 24224788 TI - Population genetic structure of the acanthocephalan Acanthosentis cheni in anadromous, freshwater, and landlocked stocks of its fish host, Coilia nasus. AB - The acanthocephalan Acanthosentis cheni was found in anadromous, freshwater, and landlocked stocks of its fish host, Coilia nasus. To examine the genetic variations of the acanthocephalan among the 3 populations with the adaptation of the host to the freshwater, the genetic structure of the helminth was investigated in anadromous (Zhoushan and Chongming islands, and Anqing), freshwater (Anqing, Ezhou, and Poyang Lake), and landlocked (Tian'ezhou Reserve) populations by sequencing intergenic transcribed spacers (ITS) of the ribosomal RNA coding genes. Low Fst values and high gene flow were found among the 7 populations (Fst = 0.0135, P = 0.2723; Nm = 36.48) and the 3 ecotypes of Acanthosentis cheni (Fst = 0.0178, P = 0.1044; Nm = 27.67). On the other hand, significant genetic differentiation of the C. nasus host populations was detected between the upstream and downstream areas of Xiaogu Mountain (Fst = 0.1961, P = 0.0030; Nm = 2.05), which is the farthest location of spawning migration for C. nasus . However, the migration break of the fish host appeared not to cause significant genetic differentiation of A. cheni populations between the upper and lower reaches of Xiaogu Mountain. Other factors might promote genetic exchange of A. cheni populations such as dispersal of the intermediate host by flooding or other fish species serving as the definitive or paratenic hosts. In Anqing, nucleotide diversity of the acanthocephalan was highest in the freshwater population (0.0038) and lower in the anadromous population (0.0026). This suggested that new mutations may have occurred in the freshwater A. cheni population in Anqing when adapting to a freshwater environment. PMID- 24224789 TI - Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. AB - AIM: Metabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. METHODS: Female mice were fed either a western (W) or low-fat control (L) semisynthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. RESULTS: Male offspring exposed to prenatal and post-weaning western-style diet (WW) showed hepatomegaly combined with accumulation of hepatic cholesterol and triglycerides. This accumulation was associated with up-regulation of de novo lipid synthesis, inflammation and dysregulation of lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histopathological analysis revealed the presence of advanced steatohepatitis in WW offspring. In addition, alterations in DNA methylation in key metabolic genes (Ppara, Insig, and Fasn) were detected. CONCLUSION: Maternal dietary fat intake during early development programmes susceptibility to liver disease in male offspring, mediated by disturbances in lipid metabolism and inflammatory response. Long-lasting epigenetic changes may underlie this dysregulation. PMID- 24224791 TI - Vanadium thiolate complexes for efficient and selective sulfoxidation catalysis: a mechanistic investigation. AB - The structural and electronic properties as well as the catalytic activity toward sulfoxidation of two new vanadium complexes have been investigated. They both possess in their coordination sphere two alkyl thiolate ligands: a dioxido V(V) complex [VO2L(NS2)](HNEt3) (1) (L(NS2) = 2,2'-(pyridine-2,6-diyl)bis(1,1' diphenylethanethiol)) and an oxido V(IV) complex [VOL(N2S2)] (2) (L(N2S2) = 2,2' (2,2'-bipyridine-6,6'-diyl)bis(1,1'-diphenylethanethiol)). The X-ray structure of 1 has revealed that the V(V) metal ion is at the center of a distorted trigonal bipyramid. The optimized structure of 2 obtained by DFT calculations displays a square-pyramidal geometry, consistent with its EPR spectrum characterized by an axial S = 1/2 signal (g? = 1.988, g? = 1.966, Ax(V) = 45 * 10(-4) cm(-1), Ay(V) = 42 * 10(-4) cm(-1), Az(V) = 135 * 10(-4) cm(-1)). DFT calculations have shown that the HOMO (highest occupied molecular orbital) of 1 is notably localized on the two thiolate sulfur atoms (56% and 22%, respectively), consistent with the expected covalent character of the V(V)-S bond. On the other hand, the SOMO (singly occupied molecular orbital) of 2 is exclusively localized at the V(IV) ion (92%). Complexes 1 and 2 have shown an ability to catalytically oxidize sulfide into sulfoxide. The oxidation reactions have been carried out with thioanisole as substrate and hydrogen peroxide as oxidant. Yields of 80% and 75% have been obtained in 10 and 15 min for 1 and 2, respectively. However, in terms of conversion, 1 is more efficient than 2 (81% and 44%, respectively). More importantly, the reaction is completely selective with no trace of sulfone produced. While 1 displays a poor stability, catalyst 2 shows the same efficiency after five successive additions of oxidant and substrate. The difference in reactivity and stability between both complexes has been rationalized through a mechanism study performed by means of experimental data ((51)V NMR and EPR spectroscopy) combined with theoretical calculations. It has been shown that the structure of the cis-oxo peroxo V(V) intermediate species, which is related to its stability, can partly explain these discrepancies. PMID- 24224790 TI - Reporting the presence of three different diseases causing GJB2 mutations in a consanguineous deaf family. AB - OBJECTIVE: This paper reports a consanguineous deaf family with three different mutations in the GJB2 gene. DESIGN: Four members of an Iranian deaf family were recruited in this study. The GJB2 coding region and exon-intron boundaries were investigated using direct sequencing. STUDY SAMPLE: The proposita was a 12-year old girl with congenital non-syndromic hearing loss. She was born to consanguineous parents. The proposita, her parents and deaf maternal uncle were screened for GJB2 mutations. RESULTS: Sequencing demonstrated the presence of the c.176_191del and c.327_328delGGinsA mutations in the proposita, the c.176_191del mutation in her father, and the c.35delG and c.327_328delGGinsA mutations in trans in her apparently unaffected mother as well as in her congenitally deaf uncle. Follow-up pure-tone audiometry revealed moderate to severe mid- and high frequency hearing loss in the mother. CONCLUSIONS: This study shows the complexity of genetic testing and counseling for hearing loss. PMID- 24224792 TI - 'My special time': Australian women's experiences of accessing a specialist perinatal and infant mental health service. AB - Women who have few social supports, poor health and a history of stressful life events are at risk of poor mental health during the perinatal period. Infants of parents whose parenting capacity is compromised are also at risk of adverse outcomes. Specifically, poor perinatal mental health can impact maternal-infant attachment. To identify women at risk of poor perinatal mental health, psychosocial assessment and depression screening in the antenatal and early postnatal periods are recommended. This qualitative study is part of a larger mixed methods study, which explored two specialist perinatal and infant mental health (PIMH) services in New South Wales (Australia). Eleven women who had accessed and been discharged from a PIMH service participated in either face-to face or telephone interviews. Data were transcribed verbatim and analysed thematically. One overarching theme, 'my special time' and three sub-themes, 'there is someone out there for me', 'it wasn't just a job' and 'swimming or stranded: feelings about leaving the service', were identified. The themes describe the women's experiences of being a client of a PIMH service. Overall, women reported a positive experience of the service, their relationship with the clinician being a key component. Findings from this study highlight the importance of the relational aspect of care and support; however, women need self determination in all therapeutic processes, including discharge, if recovery and self-efficacy as a mother are to be gained. Importantly, further research is needed about how clinicians model a secure base and how mothers emulate this for their infants. PMID- 24224793 TI - Graphene blisters with switchable shapes controlled by pressure and adhesion. AB - We created graphene blisters that cover and seal an annular cylinder-shaped microcavity in a SiO2 substrate filled with a gas. By controlling the pressure difference between the gas inside and outside of the microcavity, we switch the graphene membrane between multiple stable equilibrium configurations. We carried out experiments starting from the situation where the pressure of the gas inside and outside of the microcavity is set equal to a prescribed charging pressure, p0 and the graphene membrane covers the cavity like an annular drum, adhered to the central post and the surrounding substrate due to van der Waals forces. We decrease the outside pressure to a value, pe which causes it to bulge into an annular blister. We systematically increase the charging pressure by repeating this procedure causing the annular blister to continue to bulge until a critical charging pressure pc(i) is reached. At this point the graphene membrane delaminates from the post in an unstable manner, resulting in a switch of graphene membrane shape from an annular to a spherical blister. Continued increase of the charging pressure results in the spherical blister growing with its height increasing, but maintaining a constant radius until a second critical charging pressure pc(o) is reached at which point the blister begins to delaminate from the periphery of the cavity in a stable manner. Here, we report a series of experiments as well as a mechanics and thermodynamic model that demonstrate how the interplay among system parameters (geometry, graphene stiffness (number of layers), pressure, and adhesion energy) results in the ability to controllably switch graphene blisters among different shapes. Arrays of these blisters can be envisioned to create pressure-switchable surface properties where the difference between patterns of annular versus spherical blisters will impact functionalities such as wettability, friction, adhesion, and surface wave characteristics. PMID- 24224794 TI - Hytramycins V and I, anti-Mycobacterium tuberculosis hexapeptides from a Streptomyces hygroscopicus strain. AB - Thirty-five thousand actinomycete extracts were screened for anti-Mycobacterium tuberculosis (M. tb) activity, followed by C18 cartridge fractionation of 37 prioritized extracts. Based on MICs against replicating and nonreplicating M. tb, and IC50 values against Vero cells to generate selectivity indices, seven fractions from seven different strains were selected for further examination. When cultured in G.S.S. media and extracted with ethyl acetate, the Streptomyces hygroscopicus strain ECUM 14046 yielded an extract with promising anti-M. tb activity and a well-defined chromatographic profile. Fractionation by preparative HPLC and subsequent structure elucidation of two active fractions using 1D- and 2D-NMR and MS methods revealed the presence of two cyclohexapeptides, hytramycins V and I, each containing three unusual piperazic acid moieties. The use of (1)H iterative full spin analysis (HiFSA) on both hytramycins confirmed that quantum mechanics-simulated spectra match the experimental data, and all J(H,H) and deltaH values are consistent with the proposed structures. The absolute configuration of each amino acid moiety was determined by Marfey's method. The MICs against replicating and, more importantly, nonreplicating M. tb fall into the range of some existing second-line anti-TB drugs, such as streptomycin and capreomycin, respectively. The activities were maintained against M. tb strains that represent the major global clades, as well as H37Rv-isogenic strains that are resistant to individual clinical anti-TB drugs. PMID- 24224795 TI - Characterization of Fe-leonardite complexes as novel natural iron fertilizers. AB - Water-soluble humic substances (denoted by LN) extracted at alkaline pH from leonardite are proposed to be used as complexing agents to overcome micronutrient deficiencies in plants such as iron chlorosis. LN presents oxidized functional groups that can bind Fe(2+) and Fe(3+). The knowledge of the environment of Fe in the Fe-LN complexes is a key point in the studies on their efficacy as Fe fertilizers. The aim of this work was to study the Fe(2+)/Fe(3+) species formed in Fe-LN complexes with (57)Fe Mossbauer spectroscopy under different experimental conditions in relation to the Fe-complexing capacities, chemical characteristics, and efficiency to provide iron in hydroponics. A high oxidation rate of Fe(2+) to Fe(3+) was found when samples were prepared with Fe(2+), although no well-crystalline magnetically ordered ferric oxide formation could be observed in slightly acidic or neutral media. It seems to be the case that the formation of Fe(3+)-LN compounds is favored over Fe(2+)-LN compounds, although at acidic pH no complex formation between Fe(3+) and LN occurred. The Fe(2+)/Fe(3+) speciation provided by the Mossbauer data showed that Fe(2+)-LN could be efficient in hydroponics while Fe(3+)-LN is suggested to be used more effectively under calcareous soil conditions. However, according to the biological assay, Fe(3+)-LN proved to be effective as a chlorosis corrector applied to iron deficient cucumber in nutrient solution. PMID- 24224796 TI - Monitoring persistent platelet reactivity in patients with unprotected left main stenting. AB - OBJECTIVE: This study sought to determine the rate and potential clinical impact of persistent platelet reactivity (PPR) in unprotected left main (ULMD) stenting. BACKGROUND: PPR under aspirin or thienopyridines is associated with acute events after angioplasty. METHODS: We prospectively included 125 patients referred for ULMD stenting. For the first 64 patients (ALMA-1), angioplasty was performed under aspirin and clopidogrel without platelet reactivity assessment. For the last 61 patients (ALMA-2), platelet reactivity was assessed before angioplasty: in patients with aspirin-related PPR, aspirin twice daily was given and in those with clopidogrel-related PPR, clopidogrel double dose or prasugrel was used. RESULTS: Overall, patients' mean age was 69 +/- 13 years, 37% were diabetic, and 37% had non-ST segment elevation myocardial infarction (NSTEMI). Patients' characteristics were similar in both studies with isolated left main in 14% and associated with 1-, 2-, or 3-vessel disease in 23%, 36%, and 27%, respectively. Mean SYNTAX score was 23 +/- 9. Procedural characteristics were similar using provisional T stenting in 69%, T stenting in 27%, and other techniques in 4%. In ALMA-2, 28% patients had PPR for aspirin, 29% for clopidogrel, and 8% for both. Aspirin twice daily was given in 28% of patients, clopidogrel double dose in 26%, and prasugrel in 31%. The rate of 1-year major adverse cardiovascular and cerebrovascular events (MACCE) was lower in ALMA-2 versus ALMA-1 (8.2% vs. 20.8%; P = 0.04) as a composite end-point of cardiovascular death or stent thrombosis (0.0% vs. 8.3%; P = 0.02). CONCLUSION: PPR under aspirin and thienopyridines is frequent in ULMD stenting and could be related to subsequent major events. PMID- 24224797 TI - Efficient heat dissipation of photonic crystal microcavity by monolayer graphene. AB - Graphene, which exhibits excellent thermal conductivity, is a potential heat dissipation medium for compact optoelectronic devices. Photonic devices normally produce large- quantity of unwanted heat, and thus, a heat dissipation strategy is urgently needed. In this study, single-layer graphene (SLG) grown by chemical vapor deposition (CVD) is used to cover the surface of a photonic crystal (PhC) cavity, where the heat flux produced by the PhC cavity can be efficiently dissipated along the in-plane direction of the SLG. The thermal properties of the graphene-capped PhC cavity were characterized by experiments and theoretical calculations. The thermal resistance of the SLG-capped PhC cavity obtained from experiments is lower than half of that of a bare PhC cavity. The temperature of a SLG-capped PhC cavity is 45 K lower than that without SLG capping under an optical power of 100 MUW. Our simulation results indicate that SLG receives the majority of the heat fluxes from the device, leading to the efficient heat dissipation. Both the experimental and simulation results suggest that the SLG is a promising material to enhance the heat dissipation efficiency for optoelectronic applications. PMID- 24224798 TI - Parathyroid lipoadenoma. PMID- 24224800 TI - Making the right moves: promoting smart growth and active aging in communities. AB - This article describes an award program sponsored by the U.S. Environmental Protection Agency for excellence in smart growth and active aging. Having examined qualitative and quantitative data, we suggest that any community can foster changes to improve the health and well-being of its aging population. Diverse winners took unique paths to change their built environments and encourage physical activity. The policy changes undertaken by the award winners have both short- and long-term benefits that are important for persons of all ages, but especially for an aging society. PMID- 24224799 TI - ADX71441, a novel, potent and selective positive allosteric modulator of the GABA(B) receptor, shows efficacy in rodent models of overactive bladder. AB - BACKGROUND AND PURPOSE: The GABAB receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder (OAB). Here, we tested a novel GABAB positive allosteric modulator (PAM) ADX71441 in models of OAB in mice and guinea pigs. EXPERIMENTAL APPROACH: Mice were left untreated or given (p.o.) vehicle (1% CMC), ADX71441 (1, 3, 10 mg kg(-1) ) or oxybutynin (100 mg kg(-1) ; Experiment 1) or vehicle (1% CMC), baclofen (1, 3, 6 mg kg(-1) ) or oxybutynin (Experiment 2). Treated mice were then overhydrated with water, challenged with furosemide, before being placed into micturition chambers and monitored for urinary parameters. In anaesthetized guinea pigs, intravesical infusion of acetic acid was used to induce OAB and the effects of ADX71441 (1, 3 mg kg(-1) ) or baclofen (1 mg kg(-1) ), administered i.v., on cystometric parameters were monitored. KEY RESULTS: In mice, 10 mg kg(-1) ADX71441 increased urinary latencies, reduced the number of urinary events and the total and average urinary volumes. In guinea pigs, ADX71441 (1 and 3 mg kg( 1) ) increased the intercontraction interval (ICI) and bladder capacity (BC), and reduced micturition frequency (MF) compared to vehicle. At 3 mg kg(-1) ADX71441 completely inhibited the micturition reflex and induced overflow incontinence in five out of 10 animals. Baclofen slightly increased ICI and BC and reduced MF. CONCLUSION AND IMPLICATIONS: Our findings demonstrate, for the first time, that a GABAB PAM has potential as a novel approach for the treatment of OAB. PMID- 24224801 TI - Transforming Suzuki-Miyaura cross-couplings of MIDA boronates into a green technology: no organic solvents. AB - New technology has been developed that enables Suzuki-Miyaura couplings involving widely utilized MIDA boronates to be run in water as the only medium, mainly at room temperature. The protocol is such that no organic solvent is involved at any stage; from the reaction through to product isolation. Hence, using the E factor scale as a measure of greenness, the values for these cross-couplings approach zero. PMID- 24224802 TI - Psychological distress in mothers of children admitted to a nutritional rehabilitation unit in Malawi - a comparison with other paediatric wards. AB - In a previous study we found a very high prevalence of psychological distress in mothers of children admitted to a nutritional rehabilitation unit (NRU) in Malawi, Africa. The objective of this study was to compare the prevalence and severity of maternal distress within the NRU with that in other paediatric wards. Given the known association between poor maternal psychological well-being and child undernutrition in low- and middle-income countries, we hypothesised that distress would be higher among NRU mothers. Mothers of consecutive paediatric inpatients in a NRU, a high-dependency (and research) unit and an oncology ward were assessed for psychological distress using the Self-Reporting Questionnaire (SRQ). Two hundred sixty-eight mothers were interviewed (90.3% of eligible). The prevalence of SRQ score >=8 was 35/150 {23.3% [95% confidence interval (CI) 16.8- 30.9%]} on the NRU, 13/84 [15.5% (95% CI 8.5-25.0%)] on the high-dependency unit and 7/34 [20.6% (95% CI 8.7-37.9%)] on the oncology ward (chi(2) = 2.04, P = 0.36). In linear regression analysis, the correlates of higher SRQ score were child diarrhoea on admission, child diagnosed with tuberculosis, and maternal experience of abuse by partner; child height-for-age z-score fell only just outside significance (P = 0.05). In summary, we found no evidence of greater maternal distress among the mothers of severely malnourished children within the NRU compared with mothers of paediatric inpatients with other severe illnesses. However, in support of previous research findings, we found some evidence that poor maternal psychological well-being is associated with child stunting and diarrhoea. PMID- 24224803 TI - Synthesis of porous hierarchical MgO and its superb adsorption properties. AB - The porous hierarchical MgO with superb adsorption properties has been synthesized by a facile and scaled-up method. The X-ray powder diffraction, electron microscopy, Fourier transformed infrared, and N2 adsorption-desorption were carried out to study the microstructure of the as-synthesized precursor and product. It has been demonstrated that the as-prepared MgO has a porous hierarchical structure and a high specific surface area (148 m(2) g(-1)). And the MgO sample exhibited super adsorption properties, with maximum adsorption capacity of 2409 mg g(-1) for Congo red, which is the highest reported value. Moreover, the adsorption process of Congo red on porous hierarchical MgO was systematically investigated, which was found to obey the pseudo-second-order rate equation and Langmuir adsorption model. PMID- 24224804 TI - Allogeneic transplantation in multiple myeloma. AB - Allogeneic transplantation has the potential to cure subgroups of patients with multiple myeloma, but its role is controversial due to high transplant-related mortality. Therefore, myeloablative allogeneic transplantation has fallen out of favor. Allogeneic transplantation using reduced-intensity conditioning (RICallo) has lower transplant-related mortality and may be an option for subgroups of patients. Upfront tandem autologous/RICallo (auto/RICallo) was shown to be superior to single auto or tandem auto/auto in both progression-free and overall survival in two studies with long-term follow-up, while four similarly designed studies with shorter follow-up did not show a significant advantage. All studies included patients less than 70 years of age. No study has shown that the auto/RICallo approach is inferior to auto or auto/auto. There have been indications that poor-risk cytogenetics may be overcome by the auto/RICallo approach. Encouraging results have also been seen in treatment of relapsed patients. Small studies indicate that combining allogeneic transplant with new proteasome inhibitors and immunomodulatory drugs may further improve results. Prospective studies including these drugs for induction, conditioning and post allogeneic transplant maintenance are warranted and planned. New cell therapies, such as with natural killer cells have shown encouraging results in experimental animals and should be tried in combination with allotransplantation. PMID- 24224805 TI - Morphological and color differences between island and mainland populations in the Mexican red rump tarantula, Brachypelma vagans. AB - The introduction of species into new ecosystems, especially in small and isolated regions such as islands, offers an excellent opportunity to answer questions of the evolutionary processes occurring in natural conditions on a scale that could never be achieved in laboratory conditions. In this study, we examined the Mexican red rump tarantula Brachypelma vagans Ausserer (Mygalomorphae: Theraphosidae), a species that was introduced to Cozumel Island, Mexico, 40 years ago. This introduction provides an exceptional model to study effects such as morphological variation between island populations and those on the mainland in open habitats facing the island. Intraspecific variation related to the color polymorphism was compared. The aim of this study was to determine the phenotypic differences between continental populations of B. vagans and the introduced population on Cozumel Island. Phenotypic difference was evaluated using two approaches: 1) comparison of the morphometric measurements of adult and juvenile individuals at the local scale and between continental and island populations, and 2) comparison of individual color polymorphism between mainland and island populations. Two locations were sampled within the continental part of the Yucatan peninsula and two on the island of Cozumel. The number of samples analyzed at each site was 30 individuals. The morphometric results showed significant differences between continental and island populations, with bigger individuals on the island. In addition, three new variations of the typical color pattern of B. vagans recorded so far were observed. This study opens the door to further investigations to elucidate the origin of the phenotypic variation of the isolated individuals on Cozumel Island. Also, the widest range of color morphs found for a tarantula species is reported. PMID- 24224807 TI - New donor-pi-acceptor type triazatruxene derivatives for highly efficient dye sensitized solar cells. AB - A new class of organic dyes based on triazatruxene have been designed and synthesized for dye-sensitized solar cells. The photoelectronic properties of these donor-pi-acceptor dyes can be tuned by changing pi-conjugated linkers. The best performance was found for triazatruxene dye TD1, wherein, with thiophene as the conjugated linker and cyanoacrylic acid as the acceptor, a power conversion efficiency up to 6.10% was achieved. PMID- 24224806 TI - Microbially enhanced dissolution of HgS in an acid mine drainage system in the California Coast Range. AB - Mercury sulfides (cinnabar and metacinnabar) are the main ores of Hg and are relatively stable under oxic conditions (Ksp = 10-54 and 10-52 , respectively). However, until now their stability in the presence of micro-organisms inhabiting acid mine drainage (AMD) systems was unknown. We tested the effects of the AMD microbial community from the inoperative Hg mine at New Idria, CA, present in sediments of an AMD settling pond adjacent to the main waste pile and in a microbial biofilm on the surface of this pond, on the solubility of crystalline HgS. A 16S rRNA gene clone library revealed that the AMD microbial community was dominated by Fe-oxidizing (orders Ferritrophicales and Gallionellas) and S oxidizing bacteria (Thiomonas sp.), with smaller amounts (<= 6%) being comprised of the orders Xanthomondales and Rhodospirillales. Though the order Ferritrophicales dominate the 16S rRNA clones (>60%), qPCR results of the microbial community indicate that the Thiomonas sp. represents ~55% of the total micro-organisms in the top 1 cm of the AMD microbial community. Although supersaturated with respect to cinnabar and metacinnabar, microcosms inoculated with the AMD microbial community were capable of releasing significantly more Hg into solution compared to inactivated or abiotic controls. Four different Hg containing materials were tested for bacterially enhanced HgS dissolution: pure cinnabar, pure metacinnabar, mine tailings, and calcine material (processed ore). In the microcosm with metacinnabar, the presence of the AMD microbial community resulted in an increase of dissolved Hg concentrations up to 500 MUg L -1during the first 30 days of incubation. In abiotic control microcosms, dissolved Hg concentrations did not increase above 100 ng L-1 . When Hg concentrations were below 50 MUg L-1 , the Fe-oxidizing bacteria in the AMD microbial community were still capable of oxidizing Fe(II) to Fe(III) in the AMD solution, whereas concentrations above 50 MUg L-1 resulted in inhibition of microbial iron oxidation. Our experiments show that the AMD microbial community contributes to the dissolution of mercury sulfide minerals. These findings have major implications for risk assessment and future management of inoperative Hg mines worldwide. PMID- 24224808 TI - Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan. AB - BACKGROUNDS: Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori. METHODS: We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test. RESULTS: Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens. CONCLUSION: All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis. PMID- 24224809 TI - Differentiation between Trypanosoma cruzi and Trypanosoma rangeli using heat shock protein 70 polymorphisms. AB - OBJECTIVE: Differential diagnosis of infection with Trypanosoma cruzi or T. rangeli is relevant for epidemiological studies and clinical practice as both species infect humans, but only T. cruzi causes Chagas' disease. Their common antigen determinants complicate the distinction between both species, while current PCR assays used for differentiation show some drawbacks. We developed and validated a generic PCR discriminating the species by restriction fragment length polymorphism (RFLP) analysis and a duplex PCR specifically amplifying a differently sized fragment of both species. METHODS: The assays are based upon a partial region of the heat-shock protein 70 gene (hsp70). The analytical sensitivity and specificity were determined for both PCRs. The assays were analytically evaluated on a panel of six T. cruzi, one T. cruzi marinkellei and four T. rangeli strains, various other infectious pathogens, a panel of spiked samples of T. cruzi, and artificially mixed infections of T. cruzi and T. rangeli. Finally, the tools were applied on 36 additional isolates of Trypanosoma species. RESULTS: The detection limit of the PCRs was between 0.05 and 0.5 parasite genomes, and 1-10 parasites spiked in 200 MUl blood. In artificial mixtures, PCR-RFLP picked up both species in ratios up to 10(2) and duplex PCR up to 10(4) . In the 36 isolates tested, both single and mixed infections were identified. All assays were shown to be specific. CONCLUSION: Our PCRs show high potential for the differential diagnosis of T. cruzi and T. rangeli, which in view of their sensitivity can aid in the confirmation of infection with these parasites in vectors, reservoirs and clinical samples. PMID- 24224810 TI - Dichelyne (Cucullanellus) tornquisti n. sp. (Nematoda: Cucullanidae) from corocoro grunt, Orthopristis ruber (Cuvier, 1830) (Perciformes: Haemulidae) from Southeastern Brazil. AB - Dichelyne (Cucullanellus) tornquisti n. sp. is described from the intestine of the marine fish Orthopristis ruber (Haemulidae) of Rio de Janeiro, Brazil. The new species differs from the congeners by the location of the deirids (same level) and the excretory pore (posterior) in relation to esophagus-intestinal junction and by papillae 5 to 9 not forming a subventral line. It is the first Dichelyne species described from fish family Haemulidae in the Brazilian coastal zone. PMID- 24224812 TI - Second ISIRV International Symposium on Neglected Influenza Viruses special issue. PMID- 24224811 TI - Kinetic mechanisms of mutation-dependent Harvey Ras activation and their relevance for the development of Costello syndrome. AB - Costello syndrome is linked to activating mutations of a residue in the p-loop or the NKCD/SAK motifs of Harvey Ras (HRas). More than 10 HRas mutants that induce Costello syndrome have been identified; G12S HRas is the most prevalent of these. However, certain HRas p-loop mutations also are linked to cancer formation that are exemplified with G12V HRas. Despite these relations, specific links between types of HRas mutations and diseases evade definition because some Costello syndrome HRas p-loop mutations, such as G12S HRas, also often cause cancer. This study established novel kinetic parameter-based equations that estimate the value of the cellular fractions of the GTP-bound active form of HRas mutant proteins. Such calculations differentiate between two basic kinetic mechanisms that populate the GTP-bound form of Ras in cells. (i) The increase in the level of GTP bound Ras is caused by the HRas mutation-mediated perturbation of the intrinsic kinetic characteristics of Ras. This generates a broad spectrum of the population of the GTP-bound form of HRas that typically causes Costello syndrome. The upper end of this spectrum of HRas mutants, as exemplified by G12S HRas, can also cause cancer. (ii) The increase in the level of GTP-bound Ras occurs because the HRas mutations perturb the action of p120GAP on Ras. This causes production of a significantly high population of the only GTP-bound form of HRas linked merely to cancer formation. HRas mutant G12V belongs to this category. PMID- 24224813 TI - Comparison of influenza A virus infection in high- and low-birth-weight pigs using morphometric analysis. AB - BACKGROUND: Epigenetic studies have shown that low-birth-weight (LBW) and growth restriction has been associated with reduced immune function in humans and reduced passive immunity in pigs. To examine the immune responses of high-birth weight (HBW) and LBW groups of pigs, influenza A virus infection was used as an exemplifier of neonatal respiratory disease. OBJECTIVES: The objectives of this study were (i) to compare clinical, immunological, and pathological outcome of influenza infection in HBW to LBW pigs and (ii) to establish standardized sampling sites, score each site independently with set criteria, and compare scores between sites. METHODS: Sixty-eight 4-week-old pigs originating from either HBW or LBW litters were intratracheally inoculated with 10(6.3) TCID50 /ml of A/swine/Texas/4199-2/1998 H3N2 and euthanized 48 hours later. Samples were collected 2.5 cm from the tip of both cranial and middle lung lobes. The formalin fixed paraffin-embedded tissue sections were scored in a blinded manner by a single pathologist using established scoring criteria for routine and immunohistochemical stains. Clinical parameters, lung and nasal swab virus titers, and cytokine levels for interferon-alpha and interleukin-1-beta, IL-6, and IL-8 were measured. RESULTS AND CONCLUSIONS: Lung lesion severity and influenza staining intensity were significantly lower in LBW compared with HBW pigs (P < 0.05). Additionally, examining just the LBW group, the significant difference between lobes (P = 0.009) showed that the mean score for the right cranial lung lobe was higher compared with the other three lobes. PMID- 24224814 TI - Swine influenza: clinical, serological, pathological, and virological cross sectional studies in nine farms in Argentina. AB - BACKGROUND: Influenza A viruses (IAV) are important pathogens responsible for economic losses in the swine industry and represent a threat to public health. In Argentina, clinical, pathological, and virological findings suggest that IAV infection is widespread among pig farms. In addition, several subtypes of IAV, such as pH1N1, H3N2, delta1H1N1, and delta2H1N2, have been reported. OBJECTIVES: To evaluate the infection patterns of influenza virus in nine pig farms in Argentina. METHODS: Clinical, serological, pathological, and virological cross sectional studies were conducted. RESULTS: Clinical and pathological results were characteristic of endemic influenza infection in eight of the nine farms studied. By rRT-PCR, six of the nine farms were positive to influenza. Five IAV were obtained. Genome analysis determined that four of the isolations were pH1N1 and that the remaining one was a reassortant human origin H3N2 virus containing pandemic internal genes. Serological results showed that all farms were positive to influenza A antibodies. Moreover, the hemagglutination inhibition test showed that infection with viruses containing HA's from different subtypes (pH1, delta1H1, delta2H1, and H3) is present among the farms studied and that coinfections with two or more subtypes were present in 80.5% of positive pigs. CONCLUSIONS: Because vaccines against IAV are not licensed in Argentina, these results reflect the situation of IAV infection in non-vaccinated herds. This study provides more information about the circulation and characteristics of IAV in a poorly surveyed region. This study provides more data that will be used to evaluate the tools necessary to control this disease. PMID- 24224815 TI - Epidemiological survey of swine influenza A virus in the wild boar population of two Italian provinces. AB - OBJECTIVES: An epidemiological survey was carried out in order to obtain a better understanding of the role of wild boars in the epidemiology of the influenza virus. DESIGN: The samples were submitted to Real-Time PCR testing for gene M of the swine influenza virus (SIV), and virus isolation was performed from the positive PCR samples. Genome sequence analysis was performed on the isolates. Additionally, 1,977 boar sera samples were analyzed using ELISA and hemoagglutination inhibition. SETTING: Over recent years, the wild boar population has greatly increased in Italy, including in areas of high-density industrial pig farming, where the influenza virus is widespread. From July to December 2012, wild boar lung samples were collected in the Parma and Piacenza area, in the Emilia Romagna region. SAMPLE: 354 wild boar lung samples were collected. MAIN OUTCOME MEASURES: Wild-boar influenza A virus infection should be studied more broadly in order to obtain a better understanding of the epidemiological role played by this species. RESULTS: Three SIV strains were isolated out of 12 samples that resulted positive using PCR analysis and they were identified as avian-like SIV subtype H1N1. Phylogenetic analysis of the sequences obtained from isolate A/wild boar/291320/2012 showed that it clustered with recent Italian avian-like H1N1 SIVs isolated from domestic pigs. Sixty-eight sera samples showed a positive titer to the isolate A/wild boar/291320/2012. CONCLUSIONS: This study suggests that SIV actively circulates in the wild boar population in the investigated. area. PMID- 24224816 TI - Swine influenza in Norway: a distinct lineage of influenza A(H1N1)pdm09 virus. AB - BACKGROUND: Since the influenza A(H1N1)pdm09 virus was first introduced to the Norwegian pig population in September 2009, it has repeatedly been detected in pigs in Norway. No other subtypes of influenza virus are circulating in Norwegian pigs. OBJECTIVE: To follow the diversity of A(H1N1)pdm09 viruses circulating in pigs in Norway and to investigate the relationship between viruses circulating in Norwegian pigs and in humans. METHODS: Between January 2011 and January 2013, nasal swabs from 507 pigs were tested for A(H1N1)pdm09 virus by real-time RT-PCR. The hemagglutinin (HA) gene of virus-positive samples was sequenced and compared with publically available sequences from viruses circulating in humans at the time. RESULTS: Sequencing and phylogenetic analysis of the HA gene showed that the A(H1N1)pdm09 virus circulating in Norwegian pigs early in 2011 resembled the A(H1N1)pdm09 virus circulating in humans during this time. Viruses detected in pigs by the end of 2011 had acquired four characteristic amino acid substitutions (N31D, S84I S164F, and N473D) and formed a distinct phylogenetic group. CONCLUSIONS: A(H1N1)pdm09 virus detected in Norwegian pigs by the end of 2011 formed a distinct genetic lineage. Also, our findings indicate that reverse zoonotic transmission from humans to pigs of the A(H1N1)pdm09 virus is still important. PMID- 24224817 TI - Awareness and practices regarding zoonotic influenza prevention in Romanian swine workers. AB - BACKGROUND: Swine workers may play a key role in transmission of zoonotic influenza viruses. At the same time, little is known about the extent and effectiveness of influenza prevention programs for these at-risk workers. OBJECTIVES: To characterize practices and attitudes regarding zoonotic influenza transmission among swine workers in Romania. METHODS: We conducted a convenience survey of swine workers in Romania. The confidential survey included questions about awareness of zoonotic influenza risk, work tasks performed, flu vaccination status, and reported influenza-like illness. RESULTS: A total of 103 workers at seven farms completed the survey. The percentage of workers reporting concern about either contracting influenza from pigs or giving influenza to pigs was 78% and 70%, respectively. Although 60% of workers reported having a sick-leave policy at work, only 7% of workers reported receiving seasonal influenza vaccination during the past flu season. Only 5% of the workers reported flu-like illness during the past year while 3% of workers reported that pigs appeared sick with influenza over the same time period. The majority of workers reported using protective overalls and rubber boots during swine work, with lower rates of use of gloves. Reported use of respiratory protection was rare, and use of any personal protective equipment did not differ when pigs appeared ill. CONCLUSIONS: Despite awareness and concern regarding zoonotic influenza, Romanian swine workers report low rates of influenza vaccine or respiratory protection. As part of global pandemic influenza preparedness, enhanced prevention programs for swine workers should address such gaps. PMID- 24224818 TI - Swine influenza virus vaccine serologic cross-reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v. AB - BACKGROUND: Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. METHODS: To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. RESULTS: Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. CONCLUSIONS: Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA. PMID- 24224819 TI - Population dynamics of cocirculating swine influenza A viruses in the United States from 2009 to 2012. AB - BACKGROUND: Understanding the ecology and evolution of influenza A viruses (IAV) in mammalian hosts is critical to reduce disease burden in production animals and lower zoonotic infection risk in humans. Recent advances in influenza surveillance in US swine populations allow for timely epidemiological, phylogenetic, and virological analyses that monitor emergence of novel viruses and assess changes in viral population dynamics. METHODS: To better understand IAV in the North American swine population, we undertook a phylogenetic analysis of 1075 HA, 1049 NA, and 1040 M sequences of IAV isolated from US swine during 2009-2012 through voluntary and anonymous submissions to the US Department of Agriculture IAV swine surveillance system. RESULTS: Analyses revealed changes in population dynamics among multiple clades of A/H1N1, A/H3N2, and A/H1N2 cocirculating in US swine populations during 2009-2012. Viral isolates were categorized into one of seven genetically and antigenically distinct hemagglutinin lineages: H1alpha, H1beta, H1gamma, H1delta1, H1delta2, H1pdm09, and H3 cluster IV. There was an increase in occurrence of H1delta1 in samples submitted, with a concurrent decrease in H1pdm09. H3 cluster IV exhibited increasing diversification, warranting a re-evaluation of phylogenetic nomenclature criteria. Although H3N2 represented 25% of identified viruses, this subtype was reported in increasing proportion of sequenced isolates since late 2011. CONCLUSIONS: Surveillance and reporting of IAV in US swine have increased since 2009, and we demonstrate a period of expanded viral diversity. These data may be used to inform intervention strategies of vaccine and diagnostic updates and changes in swine health management. PMID- 24224820 TI - Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity. AB - BACKGROUND: The genetic and antigenic characteristics of influenza A viruses (IAV) within and between species change over time due to antigenic shift and drift. Although pigs are known to play a key role in the epidemiology of IAV between species, little is known about the molecular evolution of IAV hemagglutinin (HA) in pigs. OBJECTIVES: The aim of this study was to evaluate the HA drift of an H1N1 IAV after infecting weaned pigs with or without maternally derived passive immunity. METHODS: Three- to four-week-old piglets born either to vaccinated or unvaccinated sows were contact-infected upon exposure with an IAV infected pig. Nasal swabs were collected daily from each pig and tested for IAV by RRT-PCR. Full-length HA sequences were obtained directly from positive nasal swabs and compared between groups. RESULTS: Synonymous and non-synonymous mutations were detected in pigs with and without passive immunity. Most of the non-synonymous mutations occurred within the HA1 region of the HA. Changes within HA1 region were only identified in antigenic site B in pigs without passive immunity and in antigenic sites A, B, and D in pigs with passive immunity. However, there was no association between the immune status of the pig and the amino acid substitutions observed. CONCLUSIONS: Overall, we demonstrated that amino acid substitutions within antigenic sites can happen in weaned pigs with or without passive immunity shortly after infection. PMID- 24224821 TI - Epidemiological and virological investigations of equine influenza outbreaks in Ireland (2010-2012). AB - BACKGROUND: Outbreaks of equine influenza (EI) in endemic populations cause disruption and economic loss. OBJECTIVES: To identify (i) factors involved in the spread of EI (ii) virus strains responsible for outbreaks (iii) single radial haemolysis (SRH) antibody levels correlating with protection against current virus strains (iv) evidence of vaccination breakdown. METHODS: RT-PCR, virus isolation and SRH were carried out on nasopharyngeal swabs and blood samples collected from horses, ponies and donkeys on affected premises. Data relating to 629 samples from 135 equidae were analysed. RESULTS AND CONCLUSIONS: Outbreaks were sporadic, self limiting and associated with the movement of horses. Vaccination status and age influenced clinical signs of disease while housing and fomites contributed to virus spread. Subclinical infection as defined as a horse which tested positive by one or more of the following; RT-PCR, virus isolation and seroconversion in the absence of clinical signs, was identified in 9% of animals. Of the horses with up to date vaccination records 32% developed clinical signs. Vaccine breakdown occurred among horses vaccinated with all four commercially available vaccines. Analysis of HA1 sequence data generated for 26 viruses indicated that they all belonged to clade 2 of the Florida sublineage. Higher SRH antibody levels were required for both clinical and virological protection than reported in studies where vaccine strains were antigenically and genetically similar to those circulating in the field. The results of this study therefore support the OIE recommendations that vaccines be updated to include representatives of both clades of the Florida sublineage. PMID- 24224822 TI - The evaluation of a nucleoprotein ELISA for the detection of equine influenza antibodies and the differentiation of infected from vaccinated horses (DIVA). AB - BACKGROUND: Antibodies against equine influenza virus (EIV) are traditionally quantified by haemagglutination inhibition (HI) or single radial haemolysis (SRH). OBJECTIVES: To evaluate an ELISA for the detection of antibodies against influenza nucleoprotein in the diagnosis and surveillance of equine influenza (EI). METHODS: The ELISA was compared with the SRH and HI tests. Serial serum samples from 203 naturally and 14 experimentally infected horses, from 60 weanlings following primary vaccination with five different vaccines (two whole inactivated vaccines, two ISCOM-based subunit vaccines and a recombinant canarypox virus vaccine) and from 44 adult horses following annual booster vaccination with six different vaccines were analysed. RESULTS: Fewer seroconversions were detected in clinical samples by ELISA than by SRH or HI but ELISA was more sensitive than SRH in naive foals post-experimental infection. The ELISA did not detect the antibody response to vaccination with the recombinant canarypox virus vaccine confirming the usefulness of the combination of this kit and vaccine to differentiate between naturally infected and vaccinated horses, that is, DIVA. No DIVA capacity was evident with the other vaccines. CONCLUSION: The results suggest that this ELISA is a useful supplementary test for the diagnosis of EI although less sensitive than HI or SRH. It is an appropriate test for EI surveillance in a naive population and may be combined with the recombinant canarypox virus vaccine but not with other commercially available subunit vaccines, in a DIVA strategy. PMID- 24224823 TI - The genetics of virus particle shape in equine influenza A virus. AB - BACKGROUND: Many human strains of influenza A virus produce highly pleomorphic virus particles that at the extremes can be approximated as either spheres of around 100 nm diameter or filaments of similar cross-section but elongated to lengths of many microns. The role filamentous virions play in the virus life cycle remains enigmatic. OBJECTIVES/METHODS: Here, we set out to define the morphology and genetics of virus particle shape in equine influenza A virus, using reverse genetics and microscopy of infected cells. RESULTS AND CONCLUSIONS: The majority of H3N8 strains tested were found to produce filamentous virions, as did the prototype H7N7 A/eq/Prague/56 strain. The exception was the prototype H3N8 isolate, A/eq/Miami/63. Reassortment of equine influenza virus M genes from filamentous and non-filamentous strains into the non-filamentous human virus A/PR/8/34 confirmed that segment 7 is a major determinant of particle shape. Sequence analysis identified three M1 amino acid polymorphisms plausibly associated with determining virion morphology, and the introduction of these changes into viruses confirmed the importance of two: S85N and N231D. However, while either change alone affected filament production, the greatest effect was seen when the polymorphisms were introduced in conjunction. Thus, influenza A viruses from equine hosts also produce filamentous virions, and the major genetic determinants are set by the M1 protein. However, the precise sequence determinants are different to those previously identified in human or porcine viruses. PMID- 24224824 TI - Replication of avian influenza viruses in equine tracheal epithelium but not in horses. AB - We evaluated a hypothesis that horses are susceptible to avian influenza viruses by in vitro testing, using explanted equine tracheal epithelial cultures, and in vivo testing by aerosol inoculation of ponies. Results showed that several subtypes of avian influenza viruses detectably replicated in vitro. Three viruses with high in vitro replication competence were administered to ponies. None of the three demonstrably replicated or caused disease signs in ponies. While these results do not exhaustively test our hypothesis, they do highlight that the tracheal explant culture system is a poor predictor of in vivo infectivity. PMID- 24224825 TI - Biofilm mediates Enterococcus faecalis adhesion, invasion and survival into bovine mammary epithelial cells. AB - We proposed in this study that during intramammary infection, biofilm formation may facilitate adherence and colonization of Enterococcus faecalis to mammary gland epithelium. This was established by comparing six different Ent. faecalis isolates with different biofilm-forming profiles for their adhesive, invasive and survival capabilities to bovine mammary epithelial cell line (MAC-T). Our results showed increased ability of the biofilm-producer Ent. faecalis strains to adhere, invade and survive inside MAC-T cells rather than nonbiofilm-producer strains. We showed that growth of bacteria in bovine milk significantly augmented the adherence and invasion of all tested strains, and this feature was abolished again when strains were subcultured in brain heart infusion broth. Moreover, growth in bovine milk significantly increased biofilm formation by all tested strains. These results indicated that biofilm formation by Ent. faecalis, especially after expressing milk-dependent induction, may have special relevance in the pathogenesis of Ent. faecalis mastitis during intramammary infection by enhancing bovine mammary epithelial adhesion and colonization. SIGNIFICANCE AND IMPACT OF THE STUDY: Results obtained from current work highlighted the role of biofilm in the pathogenesis of Enterococcus faecalis mastitis. Those biofilm forming strains might be substantial as useful antigens in diagnostic assays and as future vaccine candidates to control Ent. faecalis mastitis. PMID- 24224826 TI - Reduction mechanisms of ethylene carbonate on si anodes of lithium-ion batteries: effects of degree of lithiation and nature of exposed surface. AB - Ab initio molecular dynamics simulations are used to identify mechanisms of reduction of ethylene carbonate on Si surfaces at various degrees of lithiation, where the low-coordinated surface Si atoms are saturated with O, OH, or H functional groups. The lowest Si content surfaces are represented by quasi amorphous LiSi4 and LiSi2; intermediate lithiation is given by LiSi crystalline facets, and the highest Li content is studied through Li13Si4 surfaces. It is found that ethylene carbonate (EC) reduction mechanisms depend significantly on the degree of lithiation of the surface. On LiSi surfaces EC is reduced according to two different two-electron mechanisms (one simultaneous and one sequential), which are independent of specific surface functionalization or nature of exposed facets. On the less lithiated surfaces, the simultaneous two-electron reduction is found more frequently. In that mechanism, the EC reduction is initiated by the formation of a C-Si bond that allows adsorption of the intact molecule to the surface and is followed by electron transfer and ring-opening. Strongly lithiated Li13Si4 surfaces are found to be highly reactive. Reduction of adsorbed EC molecules occurs via a four-electron mechanism yielding as reduction products CO(2-) and O(C2H4)O(2-). Direct transfer of two electrons to EC molecules in liquid phase is also possible, resulting in the presence of O(C2H4)OCO(2-) anions in the liquid phase. PMID- 24224830 TI - Cutting down: insights from qualitative studies of smoking in pregnancy. AB - The adverse effects of smoking in pregnancy are minimised if the mother quits completely in early pregnancy. Smokers are therefore advised to quit abruptly; cutting down is not recommended either as a method of, or alternative to, quitting. However, most pregnant smokers do not quit and cutting down is widely reported. Evidence comes primarily from quantitative studies; qualitative research has contributed little to understandings of cigarette consumption in pregnancy. In consequence, little is known about the place and meaning of cutting down for pregnant smokers. The paper investigates this important dimension of maternal smoking. It explores perceptions and experiences of cutting down among pregnant smokers by examining data from a systematic review of qualitative studies of smoking in pregnancy. The studies were located in high-income countries and published between 1970 and 2012. Twenty-six studies, reported in 29 papers, were included, representing over 640 women. Meta-ethnography guided the analysis and synthesis. Data (participants' accounts and authors' interpretations) were extracted and coded; codes were progressively combined to identify overarching themes ('lines of argument'). Running through the lines of argument was evidence on cutting down; the paper presents and analyses this evidence. The analysis indicates that cutting down figured centrally as both a method of quitting and, for persistent smokers, a method of harm reduction. While pregnant women were aware that official advice was to quit abruptly, cutting down was seen as a positive behaviour change in often-difficult domestic circumstances, and one that health professionals condoned. Our findings suggest that cutting down in pregnancy, as an aid and an alternative to quitting, requires greater recognition if healthcare and tobacco control policies are to be sensitive to the perspectives and circumstances of pregnant smokers. PMID- 24224831 TI - Thermostable recombinant beta-(1->4)-mannanase from C. thermocellum: biochemical characterization and manno-oligosaccharides production. AB - Functional attributes of a thermostable beta-(1->4)-mannanase were investigated from Clostridium thermocellum ATCC 27405. Its sequence comparison the exhibited highest similarity with Man26B of C. thermocellum F1. The full length CtManf and truncated CtManT were cloned in the pET28a(+) vector and expressed in E. coli BL21(DE3) cells, exhibiting 53 kDa and 38 kDa proteins, respectively. On the basis of the substrate specificity and hydrolyzed product profile, CtManf and CtManT were classified as beta-(1->4)-mannanase. A 1.5 fold higher activity of both enzymes was observed by Ca(2+) and Mg(2+) salts. Plausible mannanase activity of CtManf was revealed by the classical hydrolysis pattern of carob galactomannan and the release of manno-oligosaccharides. Notably highest protein concentrations of CtManf and CtManT were achieved in tryptone yeast extract (TY) medium, as compared with other defined media. Both CtManf and CtManT displayed stability at 60 and 50 degrees C, respectively, and Ca(2+) ions imparted higher thermostability, resisting their melting up to 100 degrees C. PMID- 24224832 TI - Suppression of SOS repair in E. coli: possible mechanism of antimutagenicity and protective effects of common vegetables. AB - This study aims to understand variations in antimutagenic potential of vegetables, as observed in reduction of UV-induced mutation (Rif(S)->Rif(R)) in Escherichia coli cells. On further investigation, the juice of vegetables [eggplant (small-violet), pepper (hot Arbol), bean (French), and tomato] was found to suppress mutagenic SOS response as measured by cell filamentation, LexA degradation, and induction of defective prophage as per their antimutagenic potential. Cell filamentation which was observed in 25 and 60% of the UV- and gamma-induced cells, reduced to 2-8%, and 3-16%, respectively in the presence of the vegetable juice; moreover, LexA was also not significantly affected. Phage induction frequency reduced upto 76% compared to control UV-exposed cells. The antimutagenic effect was found to be partially dependent on recB, ruvB gene functions, and was independent of uvrA function. Phenolic compounds were found to be the major contributors to the observed antimutagenicity. PMID- 24224833 TI - Mesenchymal stem cell-conditioned medium enhances osteogenic and chondrogenic differentiation of human embryonic stem cells and human induced pluripotent stem cells by mesodermal lineage induction. AB - Human mesenchymal stem cells (hMSCs) have the ability to differentiate into mesenchymal lineages. In this study, we hypothesized that treatment of embryoid bodies (EBs) composed of either human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) with a hMSC-conditioned medium (CM) can stimulate the induction of the mesodermal lineage and subsequent differentiation toward the osteogenic and chondrogenic lineage. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) analysis indicated that the hMSC-CM treatment increased gene expression related to the mesodermal lineage and decreased gene expression related to the endodermal and ectodermal lineage in EBs. Fourteen days after culturing the mesodermal lineage-induced EBs in the osteogenic or chondrogenic differentiation medium, we observed enhanced osteogenic and chondrogenic differentiation compared with untreated EBs, as evaluated using qRT-PCR, cytochemistry, immunocytochemistry, and flow cytometry. This method may be useful for enhancing the osteogenic or chondrogenic differentiation of hESCs or hiPSCs. PMID- 24224834 TI - Barrier height measurement of metal contacts to Si nanowires using internal photoemission of hot carriers. AB - Barrier heights between metal contacts and silicon nanowires were measured using spectrally resolved scanning photocurrent microscopy (SPCM). Illumination of the metal-semiconductor junction with sub-bandgap photons generates a photocurrent dominated by internal photoemission of hot electrons. Analysis of the dependence of photocurrent yield on photon energy enables quantitative extraction of the barrier height. Enhanced doping near the nanowire surface, mapped quantitatively with atom probe tomography, results in a lowering of the effective barrier height. Occupied interface states produce an additional lowering that depends strongly on diameter. The doping and diameter dependencies are explained quantitatively with finite element modeling. The combined tomography, electrical characterization, and numerical modeling approach represents a significant advance in the quantitative analysis of transport mechanisms at nanoscale interfaces that can be extended to other nanoscale devices and heterostructures. PMID- 24224835 TI - Conventional adverse features do not predict response to adjuvant chemotherapy in stage II colon cancer. AB - BACKGROUND: The role of adjuvant chemotherapy in patients with stage II colon cancer is unclear. Current guidelines recommend adjuvant chemotherapy for high risk patients, although the benefit demonstrated to date is small. Our study examined if adjuvant chemotherapy is associated with improved cancer-specific survival in high-risk patients with stage II colon cancer. METHODS: A retrospective review was performed on patients with stage II (T3-4N0M0) colon cancer in a multi-institutional database from 1999 to 2007. Additionally, histology slides were reviewed and cancer-specific survival data were obtained from the state cancer registry. Adverse features examined were perforation, obstruction, T4 disease, poor differentiation, nodal yield less than 12, lymphovascular invasion and perineural invasion. Survival analysis was performed using the Kaplan-Meier method and Cox regression. RESULTS: There were 458 patients in the study, with a median follow-up of 5.2 years. Four patients (0.8%) were lost to follow-up. There were 290 (63%) high-risk patients, defined as having at least one adverse feature. Patients who had adjuvant chemotherapy were significantly younger (median 61 years versus 72 years, P < 0.001) but had comparable ASA score (median 2 versus 2, P = 0.3). There was no significant survival benefit observed associated with any one factor or when grouped. In high risk patients the 5-year cancer specific survival with adjuvant chemotherapy was 84.8% (95% CI 78.7-91.9) compared to surgery alone 92.7% (95% CI 88.5-96.1), P = 0.85). CONCLUSION: Adjuvant chemotherapy did not significantly improve cancer specific survival in patients with stage II colon cancer with adverse features. Other markers for selecting appropriate patients for adjuvant treatment are required. PMID- 24224836 TI - Long-term results after carotid stent implantation. AB - BACKGROUND: Though carotid artery stenting (CS) has gained popularity as an alternative to carotid endarterectomy, studies examining long-term results are limited. METHODS: All consecutive patients who underwent unilateral CS between 7/1993 and 8/2005 with no or non-significant contralateral stenosis were included. Follow-up with duplex sonography and/or angiography and neurological assessment was performed at 6 and/or 12 months. Thereafter, annually, a questionnaire was sent to the patients and their referring physicians. RESULTS: Two-hundred and seventy-nine patients underwent CS. In 99% of procedures stent delivery was successful. The periprocedural major and minor stroke rates were 2.2%, respectively. The periprocedural major stroke or death rate was 2.9%. Median clinical follow-up was 49 +/- 32 months (range: 30 days-12.1 years). Excluding perioperative (<30 days) events, the annual major and minor stroke rate was 1.3% and the annual ipsilateral major and minor stroke rate was 0.6%. In symptomatic and asymptomatic patients, the annual major and minor stroke rates were 2.2% and 0.8%, respectively, and the ipsilateral major and minor stroke rates were 1.1% and 0.3%, respectively. There was no significant difference between ipsilateral and contralateral major or minor strokes at long-term follow up. At last sonographic follow-up (median 36 +/- 32 months), restenosis rates for symptomatic and asymptomatic stenoses were 5% and 3%, respectively. CONCLUSION: The results of our study demonstrate very low long-term cerebral event rates after CS supporting the long-term safety of CS. Importantly, there was no significant difference in long-term ipsilateral versus contralateral cerebral events lending support to the hypothesis of plaque stabilization. PMID- 24224837 TI - Whole-blood global DNA methylation is increased in amyotrophic lateral sclerosis independently of age of onset. AB - ALS is a heterogeneous disease that is not well understood. Epigenetic rearrangements are important in complex disorders including motor neuron diseases. The aim of this study was to determine whether whole-blood DNA methylation (DNA MET %) is a potential modifier of age at onset in ALS. DNA MET % was measured as incorporation of [(3)H]dCTP following HpaII cut in 96 ALS patients and 87 controls, comprising: early-onset (< 55 years of age) and late onset (> 74 years of age). Methionine (Met) and homocysteine (Hcy) plasma levels were assessed by liquid chromatography selected reaction monitoring coupled with isotope-dilution mass spectrometry. Results showed that DNA MET % was increased in ALS patients independently of age of onset. Compared to the other three groups, Hcy plasma levels were reduced in early-onset ALS patients but Met levels were similar. ROC analysis reported Met levels and DNA MET %, respectively, with a slight and moderate discriminative power. In conclusion, increased DNA MET % is a possible marker of epigenetic dysfunction in ALS independently of age of onset. Further studies dissecting biological determinants of phenotypic complexity in ALS may help in developing successful therapeutic strategies. PMID- 24224838 TI - Polymorphisms in the vitamin D receptor gene and risk of primary biliary cirrhosis: a meta-analysis. AB - BACKGROUND AND AIM: Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic autoimmune liver disease. Although many studies have evaluated the association between many functional polymorphisms in the vitamin D receptor (VDR) gene and PBC risk, debates still exist. Our aim is to evaluate the association between VDR gene polymorphisms, including TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and the risk of PBC by a systematic review. METHODS: We searched literatures in PubMed, SCOPUS, and EMBASE until July 2013. We calculated pooled odds ratios (OR) and 95% confidence intervals (CIs) using a fixed effects model or a random effects model for the risk to PBC associated with different VDR gene polymorphisms. And the heterogeneity assumption decided the effect model. RESULTS: A total of six relevant studies, with 1322 PBC cases and 2264 controls, were included in this meta-analysis. The results indicated that TaqI (rs731236) polymorphism was significantly associated with PBC risk (for T vs t OR = 0.75, 95% CI 0.63, 0.89, Pz = 0.001; TT + Tt vs tt OR = 0.62, 95% CI 0.44, 0.86, Pz = 0.005; OR = 0.74, 95% CI 0.58, 0.94, Pz = 0.016 for recessive model), while ApaI (rs7975232) or BsmI (rs1544410) polymorphism did not. CONCLUSION: Based on current evidences from published studies, the cumulative effect of TaqI polymorphism in VDR was significantly associated with PBC. Larger studies with mixed ethnicity subjects and stratified by clinical and sub clinical characteristics are needed to validate our findings. PMID- 24224839 TI - The safety of combined sedation with propofol plus fentanyl for endoscopy screening and endoscopic variceal ligation in cirrhotic patients. AB - OBJECTIVE: We aimed to investigate the safety of combined sedation with propofol plus fentanyl in patients with liver cirrhosis during screening esophagogastroduodenoscopy (SEGD) and a secondary prophylaxis for esophageal varices, endoscopic gastrointestinal ligation (EVL). METHODS: A total of 309 patients with liver cirrhosis were enrolled and divided into the sedated SEGD group (n = 83), the sedated EVL group (n = 137) and the conscious EVL group (n = 89), respectively, and 100 participants with no liver diseases who underwent endoscopy for gastritis were regarded as the sedated control group. Patients in the sedated groups were administrated with propofol plus fentanyl during the endoscopic procedures and their minimal hepatic encephalopathy and sedation related complications, including aspiration, hypoxia, hypotension and bradycardia, were evaluated and compared. The assessments of patient satisfaction and patient cooperation in the sedated and the conscious EVL groups were conducted. RESULTS: The incidences of complications during the endoscopic procedures were not significantly different among the sedated groups (20.5% in the sedated SEGD group, 22.6% in the sedated EVL group and 19.0% in the sedated control group). No minimal hepatic encephalopathy was induced in the sedated groups. More patients in the sedated EVL group were satisfactory with the procedure compared with the conscious EVL group, as evaluated by both endoscopists and the cirrhotic patients. CONCLUSIONS: A combined sedation with propofol plus fentanyl is safe for EVL as well as for SEGD in cirrhotic patients. Sedation might make it easier for endoscopists to perform procedures and might be more acceptable for cirrhotic patients. PMID- 24224840 TI - Effect of acclimation medium on cell viability, membrane integrity and ability to consume malic acid in synthetic wine by oenological Lactobacillus plantarum strains. AB - AIMS: The aim of this work was to evaluate the effect of acclimation on the viability, membrane integrity and the ability to consume malic acid of three oenological strains of Lactobacillus plantarum. METHODS AND RESULTS: Cultures in the stationary phase were inoculated in an acclimation medium (Accl.) containing 0, 6 or 10% v/v ethanol and incubated 48 h at 28 degrees C. After incubation, cells were harvested by centrifugation and inoculated in a synthetic wine, containing 14% v/v ethanol and pH 3.5 at 28 degrees C. Viability and membrane integrity were determined by flow cytometry (FC) using carboxyfluorescein diacetate (cFDA) and propidium iodide. Bacterial growth and malic acid consumption were monitored in a synthetic wine during 15 days. In nonacclimated strains, the damage of bacterial membranes produced a dramatic decrease in microbial viability in synthetic wine. In contrast, survival of strains previously acclimated in Accl. with 6 and 10% v/v ethanol was noticeable higher. Therefore, acclimation with ethanol increased the cultivability in synthetic wine and consequently, the consumption of l-malic acid after 15 days of growth. CONCLUSION: Acclimation of oenological strains in media containing ethanol prior to wine inoculation significantly decreases the membrane damage and improves viability in the harsh wine conditions. The role of membrane integrity is crucial to warrant the degradation of l-malic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: The efficiency of multiparametric FC in monitoring viability and membrane damage along with the malic acid consumption has a strong impact on winemaking because it represents a useful tool for a quick and highly reliable evaluation of oenological parameters. PMID- 24224841 TI - Additional data on the synlophe of Stilestrongylus aculeata (Travassos, 1918) and Stilestrongylus eta (Travassos, 1937) (Heligmonellidae) parasitic in Akodon montensis (Sigmodontinae) from the Atlantic Forest. AB - Additional data on the synlophe and morphological measurements are provided for the heligmonellids Stilestrongylus aculeata (Travassos, 1918) and Stilestrongylus eta (Travassos, 1937), collected from Akodon montensis Thomas, 1913, of the Atlantic Forest, Rio de Janeiro, Brazil. The synlophe of S. aculeata is characterized by 19 cuticular middle body ridges in males and 24 cuticular middle body ridges in females, whereas S. eta presents 17 middle body ridges in males and 20 middle body ridges in females. PMID- 24224842 TI - Design of one-dimensional coordination networks from a macrocyclic {3d-4f} single molecule magnet precursor linked by [W(CN)8]3- anions. AB - The outcome of 1:1 reactions of the tetranuclear 3d-4f Single Molecule Magnet (SMM) [Cu3Tb(L(Pr))(NO3)2(H2O)]NO3 (1) with (TBA)3[W(CN)8] (TBA = tri-n-butyl ammonium cation, [(n-Bu)3N-H](+)) in dimethylformamide (DMF) is dependent on the crystallization method employed: liquid-liquid diffusion of the reagents together gives {[Cu3Tb(L(Pr))W(CN)8(DMF)4].(DMF)}n (2) whereas diethyl ether vapor diffusion into the reaction solution gives {[Cu3Tb(L(Pr))W(CN)8(DMF)3(H2O)3].(DMF)1.5.(H2O)0.5}n (3). Both compounds are obtained as black single crystals and feature one-dimensional (1D) coordination networks (chains) of [1](3+) macrocycles linked by [W(CN)8](3-) anions. The two assemblies differ from a structural point of view. Complex 2 has a stepped arrangement with the linkers bound to the opposite faces of the macrocycle, whereas 3 has a square-wave arrangement due to the linkers binding to the same face of the macrocycle. Both compounds display an antiferromagnetic ground state below 3.5 and 2.4 K with a metamagnetic and antiferromagnetic (T, H) phase diagram for 2 and 3, respectively. Remarkably the slow dynamics of the magnetization of the [1](3+) macrocycle units is preserved in 3 while this property is quenched in 2 because of stronger intra- and interchain magnetic interactions inducing a higher critical temperature. PMID- 24224843 TI - Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity. AB - As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 +/- 0.48, 15.01 +/- 0.20, 16.82 +/- 0.42, and 4.12 +/- 0.09 MUM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents. PMID- 24224845 TI - Field emission from hybrid diamond-like carbon and carbon nanotube composite structures. AB - A thin diamond-like carbon (DLC) film was deposited onto a densely packed "forest" of vertically aligned multiwalled carbon nanotubes (VACNT). DLC deposition caused the tips of the CNTs to clump together to form a microstructured surface. Field-emission tests of this new composite material show the typical low threshold voltages for carbon nanotube structures (2 V MUm(-1)) but with greatly increased emission current, better stability, and longer lifetime. PMID- 24224844 TI - Ethanol untangles the amygdala-anxiety circuit through tonic GABA inhibition. AB - The central amygdala (CeA) has a unique role in integrating stress and the rewarding effects of ethanol (EtOH) and plays a major role in the development of EtOH dependence via signaling of corticotropin-releasing factor (CRF). A recent report by Herman and colleagues (2013) entitled "Novel Subunit-Specific Tonic GABA Currents and Differential Effects of Ethanol in the Central Amygdala of CRF Receptor-1 Reporter Mice" is the first study to investigate inhibitory tonic currents in relation to CRF signaling in the CeA. The findings of that study significantly enhance our understanding of inhibitory tonic currents in the CeA and give insight into how EtOH may differentially affect CRF signaling within the CeA, leading to the development of EtOH dependence. This commentary will focus on the recent findings of Herman and colleagues and will discuss the effects of EtOH on the entire anxiety/emotion circuitry. PMID- 24224846 TI - Effect of syringe and aggregate filter administration on survival of transfused autologous fresh feline red blood cells. AB - OBJECTIVE: To assess the effect of transfusion using a syringe and microaggregate filter on short-term survival and circulating half-life of autologous feline RBCs. DESIGN: Prospective, internally controlled, observational study. SETTING: A University Teaching Hospital ANIMALS: Six apparently healthy, owned cats. INTERVENTIONS: Blood collection by jugular venipuncture. Transfusion with labeled, autologous, fresh RBCs. MEASUREMENTS AND MAIN RESULTS: Anticoagulated whole blood (35 mL/cat) was collected in 2 equal aliquots. RBCs were washed and labeled at 2 different biotin densities, before suspension in autologous plasma. Labeled RBCs were then transfused using 2 methods, gravity flow and pump delivery using a 20 mL syringe and 18 MUm microaggregate filter. Whole blood samples were collected from each cat at 2-hour intervals for 12 hours following completion of the transfusions. Additional samples were collected at weekly intervals up to 6 weeks to assess circulating half-life of the transfused cells. Cell survival was assessed via flow cytometry. The proportion of transfused cells remaining in each of the 2 populations was measured. Biotinylated RBCs were readily detected in all cats over the 6-week sampling period. There was a significant decrease in both populations of labeled cells over the 6-week period (P < 0.01), as expected. There was no difference in probability that the RBCs would survive up to 12 hours immediately following transfusion, and no significant difference in survival between the 2 groups over 6 weeks. The average half-life of all labeled cells was approximately 23 days. CONCLUSIONS: We conclude that, in contrast to findings from dogs, transfusion of autologous feline RBCs using a syringe + aggregate filter method does not significantly impact short- or long-term survival of the transfused cells. PMID- 24224847 TI - Organ allocation in pediatric renal transplants: is there an optimal donor? AB - The 2005 revised allocation scheme for pediatric renal transplantation made the decision of whether to transplant an available living-donor (LD) kidney or use a deceased-donor (DD) kidney controversial. The aim of this study was to examine kidney allograft utilization, sensitization, and outcomes of pediatric transplant recipients. Between January 2000 and December 2009, 91 consecutive pediatric kidney recipients (<20 yr) were transplanted. The LD (n = 38) and DD (n = 53) groups were similar in age, gender, dialysis status at transplant, warm ischemia time, and overall patient survival. LD recipients were more likely to be Caucasian (92 vs. 69%), receive older allografts (39 +/- 10 vs. 23 +/- 9 yr), and have fewer human leukocyte antigen (HLA) mismatches (3.3 +/- 1.6 vs. 4.4 +/- 1.5, p < 0.01 for all). Graft survival at one, three, and five yr post-transplant was longer for LD recipients (97%, 91%, 87% vs. DD 89%, 79%, 58%, respectively, p < 0.05). At the time of transplant, 17 (33%) DD recipients had an available LD (mean age 40 yr). A greater proportion of all patients were moderately (PRA 21 79%) sensitized post-transplant (p < 0.05). A multivariable analysis of graft survival indicated that the advantage in LD organs was likely due to fewer HLA mismatched in this group. Nonetheless, LD organs appear to provide optimal outcomes in pediatric renal transplants when considering the risk of becoming sensitized post-transplant complicating later use of the LD kidney. PMID- 24224848 TI - An overview of age-friendly cities and communities around the world. PMID- 24224850 TI - All-atom molecular dynamics simulations of actin-myosin interactions: a comparative study of cardiac alpha myosin, beta myosin, and fast skeletal muscle myosin. AB - Myosins are a superfamily of actin-binding motor proteins with significant variations in kinetic properties (such as actin binding affinity) between different isoforms. It remains unknown how such kinetic variations arise from the structural and dynamic tuning of the actin-myosin interface at the amino acid residue level. To address this key issue, we have employed molecular modeling and simulations to investigate, with atomistic details, the isoform dependence of actin-myosin interactions in the rigor state. By combining electron microscopy based docking with homology modeling, we have constructed three all-atom models for human cardiac alpha and beta and rabbit fast skeletal muscle myosin in complex with three actin subunits in the rigor state. Starting from these models, we have performed extensive all-atom molecular dynamics (MD) simulations (total of 100 ns per system) and then used the MD trajectories to calculate actin-myosin binding free energies with contributions from both electrostatic and nonpolar forces. Our binding calculations are in good agreement with the experimental finding of isoform-dependent differences in actin binding affinity between these myosin isoforms. Such differences are traced to changes in actin-myosin electrostatic interactions (i.e., hydrogen bonds and salt bridges) that are highly dynamic and involve several flexible actin-binding loops. By partitioning the actin-myosin binding free energy to individual myosin residues, we have also identified key myosin residues involved in the actin-myosin interactions, some of which were previously validated experimentally or implicated in cardiomyopathy mutations, and the rest make promising targets for future mutational experiments. PMID- 24224849 TI - Substance use in clinical high risk for psychosis: a review of the literature. AB - AIM: In the literature, there is evidence suggesting an association between substance use and psychosis. However, little is known about substance use in those who may be in the pre-psychotic phase, that is, those who are putatively prodromal are considered to be at clinical high risk (CHR) of developing psychosis. METHODS: We conducted a review of publications measuring patterns and rates of substance use in CHR for psychosis individuals and the effects on the transition to psychosis. RESULTS: Of 5527 potentially relevant research papers, 10 met inclusion criteria of CHR subjects and specifically mentioned substance use in the sample. The results of these studies varied. Cannabis, alcohol and tobacco/nicotine were reported as the most commonly used substances. There was limited information on the changes in patterns of use over time. Two out of the ten studies found a significant association between the use of substances and subsequent transition to psychosis. In one of these studies, substance abuse was a predictor of psychosis when included as a variable in a prediction algorithm. In the other study, the abuse of cannabis and nicotine was associated with transition to psychosis. CONCLUSIONS: We found limited evidence to suggest that increased rates of substance use may be associated with transition to psychosis. However, further prospective research examining the association between substance use and transition to psychosis is required before any firm conclusions can be made. PMID- 24224851 TI - X-ray repair cross-complementing 1 polymorphism and prognosis of platinum-based chemotherapy in gastric and colorectal cancer: a meta-analysis. AB - BACKGROUND AND AIM: The relationships between the X-ray repair cross complementing 1 (XRCC1) Arg399Gln polymorphism (rs25487, G > A) and responses to platinum-based chemotherapy of gastric and colorectal cancer patients are controversial. Therefore, we performed a meta-analysis to assess the relationships. METHODS: We retrieved the relevant articles from MEDLINE and EMBASE databases. Fourteen studies with 1618 gastric and colorectal cancer patients were included. Primary outcomes included response rate (RR), progression free survival (PFS), and overall survival (OS). Odds ratio (OR) or hazard ratio with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software version 11.0 and Review Manager (v5.0). RESULTS: In the dominant model, the A allele of XRCC1 Arg399Gln polymorphism was associated with reduced RR to platinum-based chemotherapy in all gastric and colorectal cancer patients (A/G + A/A vs G/G OR, 0.73; 95% CI, 0.55-0.96) and in Asians (OR, 0.62; 95% CI, 0.44-0.89) but not in Caucasians (OR, 0.92; 95% CI, 0.60-1.42). In addition, stratified analysis for different types of cancers indicated a marginally significant decrease of RR in colorectal cancer patients (OR, 0.68; 95% CI, 0.46-1.00) but not in gastric cancer patients (OR, 0.78; 95% CI, 0.53 1.15). However, we did not observe a significant association between XRCC1 Arg399Gln polymorphism and hazard for PFS and OS for gastric and colorectal cancer patients in all tested models. CONCLUSIONS: XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for platinum-based chemotherapy of gastric and colorectal cancer patients, and more well-designed studies with large samples are needed to confirm our findings. PMID- 24224852 TI - Economic evaluation of sipuleucel-T immunotherapy in castration-resistant prostate cancer. AB - The objective is to examine the cost-utility of sipuleucel-T immunotherapy in asymptomatic or minimally symptomatic castration-resistant prostate cancer patients. The addition of sipuleucel-T immunotherapy to standard treatment led to a gain of 0.37 quality-adjusted life-year (QALY) at an additional cost of US$104,536. The incremental cost-utility ratio was US$283,000 per QALY saved. Threshold sensitivity analyses indicated that a price reduction of at least 53%, or application in a group of patients resulting in the relative reduction in the mortality rate of at least 39%, ought to augment the economic value of this regimen. Sipuleucel-T immunotherapy treatment at the current price with 96.5% certainty is not cost-effective. The specific group of patients who will benefit more from the treatment should be revealed and treated, or the cost of the vaccine should be lowered significantly to increase its economic value. Accounting for crossover treatment in control patients improves sipuleucel-T's value (US$132,000 per QALY saved) although further investigation is necessary. PMID- 24224853 TI - Personal care workers in Australian aged care: retention and turnover intentions. AB - AIM: This study examined factors influencing personal care workers' intentions to stay or leave Australian aged care employment - especially for older workers. BACKGROUND: Retention of personal care workers is particularly important in aged care as they provide the majority of the direct care via community aged care or long-term aged care environments. However, there is limited research on what drives their turnover and retention. METHOD: A survey was conducted during 2012 collecting 206 responses from workers within community and long-term aged care in four organisations in Australia. RESULT: Perceived supervisor support, on-the-job embeddedness and area of employment were identified as predictors of both intention to stay and to leave, although the relationship strength differed. Community care workers were more likely to stay and reported more supervisor support than long-term care workers. Unexpectedly, age and health status were not predictors of staying or leaving. CONCLUSION: While there are similarities between retention and turnover motivators, there are also differences. Within a global context of health worker shortages, such new knowledge is keenly sought to enhance organisational effectiveness and sustain the provision of quality aged care. IMPLICATIONS FOR NURSING MANAGEMENT: Retention strategies for older workers should involve increasing supervisor support, and seeking to embed workers more fully within their organisation. PMID- 24224854 TI - Evaluating food front-of-pack labelling: a pan-European survey on consumers' attitudes toward food labelling. AB - Nutrition labels on pre-packaged foods have been widely used as a medium to foster healthier eating habits in the general population, to contribute to a reduction in the incidence and prevalence of diet-related conditions. Yet, there is no convincing evidence that food labels are an effective means to achieve the desired effect at population level. Several factors have been suggested to account for this decoupling of efficacy, e.g. difficulties in understanding the information on food-labels. The present article presents the results of a survey on Europeans' understanding of nutritional labels and evaluation on the communication tools for their diffusion. A total of 7550 phone interviews were conducted in 16 European Countries: Austria, Belgium, Denmark, France, Germany, Greece, Italy, the Netherlands, Poland, Portugal, Czech Republic, Slovenia, Spain, Sweden, United Kingdom and Hungary. Consumers were asked about their opinion on nutritional information provided at different levels and their commitment to healthy behaviour. PMID- 24224855 TI - Modest long-term ethanol consumption affects expression of neurotransmitter receptor genes in the rat nucleus accumbens. AB - BACKGROUND: Over 100 million people worldwide are affected by alcohol use disorders. These conditions usually take years to develop where an initial, voluntary consumption is gradually replaced by a compulsive intake of alcohol. The exact mechanisms behind this transition remain unknown. However, ethanol (EtOH) is known to interact with several neurotransmitters and receptors in the central nervous system, and chronic EtOH consumption causes alterations in these neurotransmitter systems, proposed to contribute to the development of dependence. This study aimed to repeat previous findings that animals after long term voluntary EtOH consumption spontaneously increase their intake. That the initial encounter with EtOH causes an elevation of dopamine in the nucleus accumbens (nAc), inducing feelings of well-being and creating an incentive to continue the behavior, has been repeatedly reported in both animals and humans. The effects of chronic EtOH consumption on this region are not as well investigated. METHODS: We examined both long-term EtOH consumption behavior and its consequences on expression of neurotransmitter-related genes in the nAc of the Wistar rat using quantitative polymerase chain reaction. RESULTS: In general, the EtOH consumption of the animals in this study was modest with an average intake of 0.9 g/kg/d, and only 1 of the 24 rats consuming EtOH for 10 months drastically increased its intake in line with the results of Wolffgramm and Heyne (1995). Expression of the genes for dopamine receptor 2, MU-opioid receptor, and somatostatin receptor 4 were down-regulated in animals after 2 and/or 4, but not 10, months of EtOH consumption. CONCLUSIONS: Chronic consumption even of modest amounts of alcohol seems to affect regulation of expression of these genes, possibly leading to changes in neurotransmitter signaling. Studies are ongoing to investigate whether these alterations are specific for the nAc. PMID- 24224856 TI - Comparison of different sets of instruments for laparoendoscopic single-site surgery in a surgical simulator with novices. AB - BACKGROUND: Given the parallel entry of working instruments through a single incision in laparoendoscopic single-site surgery, loss of triangulation in the abdominal cavity and counteracting movements of the instruments are inevitable obstacles. Some specially designed devices have emerged to ameliorate these challenges. METHODS: Twenty-four novice participants were randomized into four groups using assigned instruments, conventional straight instruments, single curved instruments, double-curved instruments and articulating instruments, respectively, to perform two basic tasks (peg transferring and pattern cutting) 14 times in a modified simulator. A test of the tasks and a resection of the intestine segment of a rat were performed. The task scores and evaluation of intraoperative skills during the resection of the intestine segment were recorded. The instrument of modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) was completed. RESULTS: The task scores of the groups using single-curved instruments and articulating instruments were better than the other two groups on the simulator tasks, consistent with the evaluation of intraoperative skills during the resection of intestine segment. As the proficiency with the instruments increased, the task scores improved, as demonstrated by the learning curve. The workload measured by the modified NASA TLX tool demonstrated that the groups using articulating instruments and double curved instruments had a heavier workload in most of the categories compared with the other two groups. CONCLUSIONS: Single-curved and articulating instruments are more effective than conventional straight and double-curved devices, and are favourable in laparoendoscopic single-site surgery for novice learners. PMID- 24224857 TI - NdNiMg5, a new magnesium-rich phase with an unusual structural type. AB - The new intermetallic NdNiMg5 was discovered during the study of the Mg-rich part of the Mg-Nd-Ni system. It was synthetized by melting of the constituent elements in a sealed tantalum tube with subsequent annealing. Its structure was determined by X-ray diffraction on a single crystal. Crystal data: orthorhombic system, Cmcm, Z = 4, a = 4.4799(2) A, b = 9.9827(3) A, c = 13.7854(10) A, d(calc) = 3.49 g.cm(-3). Its structure is made of infinite layers of Mg atoms that form blocks stacked along the c axis. These blocks, with a close-packed array of Mg atoms, are separated by infinite NiNd layers and connected through short Mg-Mg bonds. In the NiNd layer, the Ni and Nd atoms form an ordered graphite-type network. Antiferromagnetic ordering is observed with T(N) = 12 K, and the effective magnetic moment MUeff is equal to 3.89(1) MUB. PMID- 24224858 TI - Examination of factors for use as potential predictors of human enteric pathogen survival in soil. AB - AIMS: Three soils that varied in their physicochemical characteristics and microbial diversity were inoculated with Escherichia coli O157:H7 and Salmonella to determine the relative impact of abiotic and biotic factors on the pathogens' survival when the soil was held at 25 degrees C. METHODS AND RESULTS: Three soils that were classified as having low, medium and high microbial diversity were divided into two batches for adjustment to 20% of water-holding capacity and to 40% of water-holding capacity. Soils were inoculated with both green fluorescent labelled E. coli O157:H7 and red fluorescent-labelled Salmonella (5 log CFU g(-1) dry weight) and held at 25 degrees C. Pathogens inoculated into an acidic soil died off within 9 weeks, whereas they were still detected in the other two soils by enrichment culture after 18 weeks. Moisture did not affect inactivation of E. coli O157:H7, but did affect Salmonella inactivation in soil having the greatest organic load and microbial diversity. Using multiple linear regression analysis, 98.7% of the variability in the inactivation rate for E. coli O157:H7 was explained by a model that included the variables of initial pH and electrical conductivity. Salmonella's inactivation rate was predicted by a model that included pH and initial cell numbers of copiotrophic and oligotrophic bacteria. CONCLUSION: This study provided evidence of specific properties that impact inactivation of E. coli O157:H7 and Salmonella in soils at 25 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of factors influential in the die-off of enteric pathogens will assist in developing guidelines for safe intervals between field contamination events and planting or harvesting of fresh cut produce crops. PMID- 24224859 TI - A review of mortality from parasitic and vector-borne diseases in the U.S. Air Force from 1970 to 2012. AB - We review a unique set of documents, death certificates, cataloged in the U.S. Air Force Mortality Registry database, which tracks deaths for all current and retired service members. We screened the records for all deaths caused by parasitic, vector-borne, or zoonotic diseases between 1970 and 2013. There were 78 deaths caused by a variety of diseases such as amebiasis, malaria, strongyloidiasis, schistosomiasis, and pneumocystosis. We compare these deaths to U.S. national deaths. U.S. Air Force service members are more likely to die from malaria, strongyloidiasis, and Q fever than the average American but are less likely to die from pneumocystosis. PMID- 24224860 TI - Prescription of antidepressants is increased in Danish patients with polycystic ovary syndrome and is associated with hyperandrogenism. A population-based cohort study. AB - OBJECTIVE: Quality of life is impaired in polycystic ovary syndrome (PCOS). In this study, we compared the time to first prescription of antidepressants (ADM) in PCOS vs two control groups. DESIGN: Register-based cohort study. PATIENTS: One thousand and one hundred and twenty-four premenopausal women with hirsutism and/or PCOS, premenopausal women with hypertension (HT, n = 301), and age- and sex-matched population controls (controls, n = 4110). MEASUREMENTS: Prescriptions for ADM on secondary care contacts from regional registers. RESULTS: The median age at cohort entry in PCOS, HT and controls was 29, 34 and 29 years, respectively. Among PCOS, HT and controls, 227 (20%), 74 (25%) and 633 (15%), respectively, had prescriptions of ADM. The median time to first prescription of ADM in the PCOS, HT and control cohorts was 6.8, 6.6 and 7.2 years, respectively. The adjusted hazard ratio for time to prescription of ADM for HT vs PCOS was 1.36 [95% CI (1.02-1.82)], P = 0.039, and for controls vs PCOS, it was 0.75 [95% CI (0.64-0.88)], P < 0.001. Within patients with PCOS, hyperandrogenism contributed significantly to the model, likelihood ratio test P = 0.009. The adjusted hazard ratio for hyperandrogenism vs no hyperandrogenism was 1.97 (1.12-3.45), P = 0.018. CONCLUSION: Patients with PCOS had moderately but significantly decreased time to first prescription of ADM compared with age-matched healthy women, whereas patients with HT had the shortest time to prescription. In PCOS, prescription of ADM was associated with the presence of hyperandrogenism. PMID- 24224861 TI - Optical diode action from axially asymmetric nonlinearity in an all-carbon solid state device. AB - Nanostructured carbons are posited to offer an alternative to silicon and lead to further miniaturization of photonic and electronic devices. Here, we report the experimental realization of the first all-carbon solid-state optical diode that is based on axially asymmetric nonlinear absorption in a thin saturable absorber (graphene) and a thin reverse saturable absorber (C60) arranged in tandem. This all-optical diode action is polarization independent and has no phase-matching constraints. The nonreciprocity factor of the device can be tuned by varying the number of graphene layers and the concentration or thickness of the C60 coating. This ultracompact graphene/C60 based optical diode is versatile with an inherently large bandwidth, chemical and thermal stability, and is poised for cost-effective large-scale integration with existing fabrication technologies. PMID- 24224862 TI - Bioactive lignans from the trunk of Abies holophylla. AB - Six new lignans (1-6) were isolated from the trunk of Abies holophylla MAXIM, together with 11 known lignans (7-17). The structures of 1-7 were elucidated by spectroscopic methods, acid hydrolysis, and use of the modified Mosher's method. The effects of the isolates on nerve growth factor induction in a C6 rat glioma cell line were evaluated. Compounds 6, 7, and 13 showed significant induction of nerve growth factor secretion at concentrations of 10 MUM. Compounds 1, 5, 6, and 16 showed moderate inhibitory effects on nitric oxide production in lipopolysaccharide-activated BV-2 cells (IC50 28.5-36.4 MUM). PMID- 24224863 TI - Rolling silver nanowire electrodes: simultaneously addressing adhesion, roughness, and conductivity. AB - Silver nanowire mesh electrodes represent a possible mass-manufacturable route toward transparent and flexible electrodes for plastic-based electronics such as organic photovoltaics (OPVs), organic light emitting diodes (OLEDs), and others. Here we describe a route that is based upon spray-coated silver nanowire meshes on polyethylene terephthalate (PET) sheets that are treated with a straightforward combination of heat and pressure to generate electrodes that have low sheet resistance, good optical transmission, that are topologically flat, and adhere well to the PET substrate. The silver nanowire meshes were prepared by spray-coating a solution of silver nanowires onto PET, in air at slightly elevated temperatures. The as-prepared silver nanowire electrodes are highly resistive due to the poor contact between the individual silver nanowires. Light pressure applied with a stainless steel rod, rolled over the as-sprayed silver nanowire meshes on PET with a speed of 10 cm s(-1) and a pressure of 50 psi, results in silver nanowire mesh arrays with sheet resistances of less than 20 Omega/?. Bending of these rolled nanowire meshes on PET with different radii of curvature, from 50 to 0.625 mm, showed no degradation of the conductivity of the electrodes, as shown by the constant sheet resistance before and after bending. Repeated bending (100 times) around a rod with a radius of curvature of 1 mm also showed no increase in the sheet resistance, demonstrating good adherence and no signs of delamination of the nanowire mesh array. The diffuse and direct transmittance of the silver nanowires (both rolled and as-sprayed) was measured for wavelengths from 350 to 1200 nm, and the diffuse transmission was similar to that of the PET substrate; the direct transmission decreases by about 7-8%. The silver nanowires were then incorporated into OPV devices with the following architecture: transparent electrode/PEDOT:PSS/P3HT:PC61BM/LiF/Al. While slightly lower in efficiency than the standard indium tin oxide substrate (ITO), the rolled silver nanowire electrodes had a very good device yield, showing that short circuits resulting from the silver nanowire electrodes can be successfully avoided by this rolling approach. PMID- 24224864 TI - Lessons learned from a Canadian province-wide age-friendly initiative: the Age Friendly Manitoba Initiative. AB - The Age-Friendly Manitoba Initiative was launched in 2008. A formative evaluation we conducted in 2011 with 44 participating rural and urban communities demonstrates considerable progress, with virtually all communities having formed an Age-Friendly Committee and conducting a community assessment to identify priorities for action. The majority of communities implemented one or more age friendly projects. Major barriers to becoming age-friendly identified by participants included lack of funding; lack of capacity, particularly in small communities; and lack of leadership or direction. The study highlights the importance of strong leadership at all levels of government (municipal, provincial, federal); the need to support communities, particularly rural ones, as they try to become more age-friendly; and the importance of ongoing promotion of age-friendliness locally and more broadly (e.g., provincially). PMID- 24224865 TI - Narrative in interprofessional education and practice: implications for professional identity, provider-patient communication and teamwork. AB - Health and social care professionals increasingly use narrative approaches to focus on the patient and to communicate with each other. Both effective interprofessional education (IPE) and practice (IPP) require recognizing the various values and voices of different professions, how they relate to the patient's life story, and how they interact with each other at the level of the healthcare team. This article analyzes and integrates the literature on narrative to explore: self-narrative as an expression of one's professional identity; the co-creation of the patient's narrative by the professional and the patient; and the interprofessional multi-vocal narrative discourse as co-constructed by members of the healthcare team. Using a narrative approach to thinking about professional identity, provider-patient communication, and interprofessional teamwork expands our thinking about both IPE and IPP by providing new insights into the nature of professional practice based on relationships to oneself, the patient, and others on the team. How professionals define themselves, gather and present information from the patient, and communicate as members of a clinical team all have important dimensions that can be revealed by a narrative approach. Implications and conclusions for the further development of the narrative approach in IPE and IPP are offered. PMID- 24224866 TI - Update on the US National Center for Interprofessional Practice and Education. PMID- 24224868 TI - Determinants of hemodialysis-induced segmental wall motion abnormalities. AB - Patients who demonstrate worsening of cardiac wall motion (WM) during hemodialysis have higher 1-year mortality. We sought to identify risk factors for dialysis-induced WM abnormalities. Additionally, we examined the effects of hemodialysis on other parameters of cardiac function. Forty patients underwent echocardiography directly before dialysis and during the last hour of dialysis (79 dialysis sessions). Candidate predictors for intradialytic worsening of WM included age, a history of heart failure (HF) or coronary artery disease, changes in blood pressure or heart rate, high sensitivity cardiac troponin T and N terminal brain natriuretic peptide. Among 40 patients, WM worsened segmentally in eight patients (20%), worsened globally in one patient (3%), and improved segmentally in four patients (10%). Diastolic function worsened in 44% of patients, and left ventricular ejection fraction was largely unchanged during dialysis. The case of globally worsened WM occurred in the setting of intradialytic hypertension in a patient without HF. Surprisingly, history of coronary artery disease, hemodynamics, and serologic factors were not associated with worsened segmental WM during dialysis. After adjustment for history of coronary artery disease and other cardiac risk factors, patients with a history of HF had a threefold higher risk of worsening segmental WM during dialysis (RR 3.1, 95% CI [1.1, 9], p = 0.04). In conclusion, patients with a history of clinical HF were at higher risk of intradialytic worsening of segmental WM. Further studies are needed to determine the mechanism of this association and whether cardioprotective medications could ameliorate this adverse cardiac effect of hemodialysis. PMID- 24224869 TI - Tendon structural adaptations to load exercise are inhibited by anabolic androgenic steroids. AB - The present study investigated the structural changes in the rat calcaneal tendon (CT), superficial flexor tendon (SFT), and deep flexor tendon (DFT) in response to jump exercises and anabolic androgenic steroids (AAS). Animals were divided into four groups: sedentary, trained, AAS-treated sedentary rats, and AAS-treated trained animals. Training increased the volume density (Vv%) of blood vessels in all regions of the CT and DFT, cell Vv% in the peritendinous sheath of the proximal and distal regions of the SFT and proximal region of DFT, and cell Vv% in the tendon proper of the proximal and distal regions of the SFT and DFT. The combination of AAS and load exercises showed little increased blood vessel Vv% at the proximal region of the CT, intermediate region of the SFT, and all regions of the DFT as opposed to an increase in adipose cell Vv% in the CT proximal region. The AAS reduced the levels of hydroxyproline in the proximal region of the DFT and in the distal region of the STF. In conclusion, exercise promoted benefits to the adaptation of the tendons to overload. These effects were absent when load exercise was combined with AAS. The abusive consumption of AAS contributes to tendon inertness and rigidity, and increases the potential risk of injury. PMID- 24224870 TI - Current concepts and future strategies in the management of intracranial germinoma. AB - Radiation therapy is the backbone in the management of intracranial germinoma. In localized disease chemotherapy followed by whole brain irradiation is the present standard providing cure rates in excess of 90%. Craniospinal irradiation alone in metastatic disease provides equally excellent outcome. Chemotherapy is able to convert macroscopic to microscopic disease permitting a dose reduction to the tumor site and possibly the ventricular system and is investigated in prospective trials. Chemotherapy alone cannot replace radiotherapy as sole treatment. Whole ventricular radiotherapy followed by a boost to tumor site without chemotherapy might be feasible. New treatment technologies such as intensity-modulated radiotherapy or proton therapy permit a dose reduction to non-target brain. Data on functional outcome are conflicting and based on small heterogeneous series only mandating prospective investigations. PMID- 24224871 TI - Molecular detection of Peronospora variabilis in quinoa seed and phylogeny of the quinoa downy mildew pathogen in South America and the United States. AB - Quinoa (Chenopodium quinoa) is an important export of the Andean region, and its key disease is quinoa downy mildew, caused by Peronospora variabilis. P. variabilis oospores can be seedborne and rapid methods to detect seedborne P. variabilis have not been developed. In this research, a polymerase chain reaction (PCR)-based detection method was developed to detect seedborne P. variabilis and a sequencing-based method was used to validate the PCR-based method. P. variabilis was detected in 31 of 33 quinoa seed lots using the PCR-based method and in 32 of 33 quinoa seed lots using the sequencing-based method. Thirty-one of the quinoa seed lots tested in this study were sold for human consumption, with seed originating from six different countries. Internal transcribed spacer (ITS) and cytochrome c oxidase subunit 2 (COX2) phylogenies were examined to determine whether geographical differences occurred in P. variabilis populations originating from Ecuador, Bolivia, and the United States. No geographical differences were observed in the ITS-derived phylogeny but the COX2 phylogeny indicated that geographical differences existed between U.S. and South American samples. Both ITS and COX2 phylogenies supported the existence of a Peronospora sp., distinct from P. variabilis, that causes systemic-like downy mildew symptoms on quinoa in Ecuador. The results of these studies allow for a better understanding of P. variabilis populations in South America and identified a new causal agent for quinoa downy mildew. The PCR-based seed detection method allows for the development of P. variabilis-free quinoa seed, which may prove important for management of quinoa downy mildew. PMID- 24224872 TI - Aspergillus parasiticus communities associated with sugarcane in the Rio Grande Valley of Texas: implications of global transport and host association within Aspergillus section Flavi. AB - In the Rio Grande Valley of Texas (RGV), values of maize and cottonseed crops are significantly reduced by aflatoxin contamination. Aflatoxin contamination of susceptible crops is the product of communities of aflatoxin producers and the average aflatoxin-producing potentials of these communities influence aflatoxin contamination risk. Cropping pattern influences community composition and, thereby, the epidemiology of aflatoxin contamination. In 2004, Aspergillus parasiticus was isolated from two fields previously cropped to sugarcane but not from 23 fields without recent history of sugarcane cultivation. In 2004 and 2005, A. parasiticus composed 18 to 36% of Aspergillus section Flavi resident in agricultural soils within sugarcane-producing counties. A. parasiticus was not detected in counties that do not produce sugarcane. Aspergillus section Flavi soil communities within sugarcane-producing counties differed significantly dependent on sugarcane cropping history. Fields cropped to sugarcane within the previous 5 years had greater quantities of A. parasiticus (mean = 16 CFU/g) than fields not cropped to sugarcane (mean = 0.1 CFU/g). The percentage of Aspergillus section Flavi composed of A. parasiticus increased to 65% under continuous sugarcane cultivation and remained high the first season of rotation out of sugarcane. Section Flavi communities in fields rotated to non-sugarcane crops for 3 to 5 years were composed of <5% A. parasiticus, and fields with no sugarcane history averaged only 0.2% A. parasiticus. The section Flavi community infecting RGV sugarcane stems ranged from 95% A. parasiticus in billets prepared for commercial planting to 52% A. parasiticus in hand-collected sugarcane stems. Vegetative compatibility assays and multilocus phylogenies verified that aflatoxin contamination of raw sugar was previously attributed to similar A. parasiticus in Japan. Association of closely related A. parasiticus genotypes with sugarcane produced in Japan and RGV, frequent infection of billets by these genotypes, and the ephemeral nature of A. parasiticus in RGV soils suggests global transport with sugarcane planting material. PMID- 24224873 TI - Homotropic cooperativity from the activation pathway of the allosteric ligand responsive regulatory trp RNA-binding attenuation protein. AB - The trp RNA-binding attenuation protein (TRAP) assembles into an 11-fold symmetric ring that regulates transcription and translation of trp-mRNA in bacilli via heterotropic allosteric activation by the amino acid tryptophan (Trp). Whereas nuclear magnetic resonance studies have revealed that Trp-induced activation coincides with both microsecond to millisecond rigidification and local structural changes in TRAP, the pathway of binding of the 11 Trp ligands to the TRAP ring remains unclear. Moreover, because each of 11 bound Trp molecules is completely surrounded by protein, its release requires flexibility of Trp bound (holo) TRAP. Here, we used stopped-flow fluorescence to study the kinetics of Trp binding by Bacillus stearothermophilus TRAP over a range of temperatures and observed well-separated kinetic steps. These data were analyzed using nonlinear least-squares fitting of several two- and three-step models. We found that a model with two binding steps best describes the data, although the structural equivalence of the binding sites in TRAP implies a fundamental change in the time-dependent structure of the TRAP rings upon Trp binding. Application of the two-binding step model reveals that Trp binding is much slower than the diffusion limit, suggesting a gating mechanism that depends on the dynamics of apo TRAP. These data also reveal that dissociation of Trp from the second binding mode is much slower than after the first Trp binding mode, revealing insight into the mechanism for positive homotropic allostery, or cooperativity. Temperature dependent analyses reveal that both binding modes imbue increases in bondedness and order toward a more compressed active state. These results provide insight into mechanisms of cooperative TRAP activation and underscore the importance of protein dynamics for ligand binding, ligand release, protein activation, and allostery. PMID- 24224874 TI - Hydrogen sensing under ambient conditions using SnO2 nanowires: synergetic effect of Pd/Sn codeposition. AB - Semiconducting SnO2 nanowires deposited with Pd and Sn nanoparticles on their surface are shown to be a highly sensitive hydrogen sensor with fast response time at room temperature. Compared with the SnO2 nanowire deposited with Pd or Sn nanoparticles alone, the Pd/Sn-deposited SnO2 nanowire exhibits a significant improvement in the sensitivity and reversibility of sensing hydrogen gas in the air at room temperature. Our investigation indicates that two factors are responsible for the synergistic effect of Pd/Sn codeposition on SnO2 nanowires. One is that in the presence of Pd the oxidation of Sn nanoparticles on the surface of the SnO2 nanowire is incomplete leading only to suboxides SnOx (1 <= x < 2), and the other is that the surface of the Pd/Sn-deposited SnO2 nanowire is almost perfectly hydrophobic. PMID- 24224875 TI - Functional insight from the tetratricopeptide repeat-like motifs of the type III secretion chaperone SicA in Salmonella enterica serovar Typhimurium. AB - SicA functions both as a class II chaperone for SipB and SipC of the type III secretion system (T3SS)-1 and as a transcriptional cofactor for the AraC-type transcription factor InvF in Salmonella enterica subsp. enterica serovar Typhimurium. Bioinformatic analysis has predicted that SicA possesses three tetratricopeptide repeat (TPR)-like motifs, which are important for protein protein interactions and serve as multiprotein complex mediators. To investigate whether the TPR-like motifs in SicA are critical for its transcriptional cofactor function, the canonical residues in these motifs were mutated to glutamate (SicAA44E , SicAA78E , and SicAG112E ). None of these mutants except SicAA44E were able to activate the expression of the sipB and sigD genes. SicAA44E still has a capacity to interact with InvF in vitro, and despite its instability in cell, it could activate the sigDE operon. This suggests that TPR motifs are important for the transcriptional cofactor function of the SicA chaperone. PMID- 24224877 TI - Perdeuterated 2,2'-bipyridine-6,6'-dicarboxylate: an extremely efficient sensitizer for thulium luminescence in solution. AB - Lanthanoid luminescence has become an important pillar for many modern photonics applications such as bioanalytical research or functional material science. So far, however, thulium despite having one of the most interesting photophysics among the lanthanoids has suffered from extremely low luminescence efficiencies in molecular complexes with organic sensitizer ligands. This has greatly hampered the investigation and application of thulium emission in solution. Here, the discovery of a powerful sensitizer for thulium photoluminescence is reported. The corresponding thulium complex exhibits emission efficiencies (quantum yield Phi > 0.12%; lifetime tauobs = 4.6 MUs; brightness epsilonPhi > 30 M(-1) cm(-1)) and can even be detected at low micromolar concentrations in high-phonon solvents like water without the need for laser excitation. PMID- 24224876 TI - Quantitative, label-free characterization of stem cell differentiation at the single-cell level by broadband coherent anti-Stokes Raman scattering microscopy. AB - We use broadband coherent anti-Stokes Raman scattering (BCARS) microscopy to characterize lineage commitment of individual human mesenchymal stem cells cultured in adipogenic, osteogenic, and basal culture media. We treat hyperspectral images obtained by BCARS in two independent ways, obtaining robust metrics for differentiation. In one approach, pixel counts corresponding to functional markers, lipids, and minerals, are used to classify individual cells as belonging to one of the three lineage groups: adipocytes, osteoblasts, and undifferentiated stem cells. In the second approach, we use multivariate analysis of Raman spectra averaged exclusively over cytosol regions of individual cells to classify the cells into the same three groups, with consistent results. The exceptionally high speed of spectral imaging with BCARS allows us to chemically map a large number of cells with high spatial resolution, revealing not only the phenotype of individual cells, but also population heterogeneity in the degree of phenotype commitment. PMID- 24224878 TI - Expression level of sonic hedgehog correlated with the speed of gastric mucosa regeneration in artificial gastric ulcers. AB - BACKGROUND AND AIM: Gastric ulcer healing is a complex process involving cell proliferation and tissue remodeling. Sonic hedgehog (Shh) activates the Shh signaling pathway, which plays a key role in processes such as tissue repair. Shh and interleukin 1beta (IL1beta) have been reported to influence the proliferation of gastric mucosa. We evaluated the relationships between the speed of gastric ulcer healing and the levels of expression of Shh and IL1beta. METHODS: The study included 45 patients (mean age 71.9 +/- 9.0 years; M/F, 30/15) who underwent endoscopic submucosal dissection (ESD) for gastric cancer, followed by standard dose of oral proton-pump inhibitor for 4 weeks. Subsequently, the size of ESD induced artificial ulcers were measured to determine the speed of gastric ulcer healing, and regenerating mucosa around the ulcers and appropriately matched controls were collected from patients by endoscopic biopsy. Polymerase chain reaction (PCR) array analysis of genes in the Shh signaling pathway was performed, and quantitative reverse transcription (RT)-PCR was used to measure IL1beta mRNA. RESULTS: The levels of Shh and IL1beta mRNA were 3.0 +/- 2.7-fold and 2.5 +/- 2.5-fold higher, respectively, in regenerating mucosa of artificial ulcers than in appropriately matched controls, with the two being positively correlated (r = 0.9, P < 0.001). Shh (r = 0.8, P < 0.001) and IL1beta (r = 0.7, P < 0.005) expression was each positively correlated with the speed of gastric ulcer healing, but multivariate analysis showed that Shh expression was the only significant parameter (P = 0.045). CONCLUSIONS: Expression of Shh was correlated with the speed of gastric ulcer healing, promoting the regeneration of gastric mucosa. PMID- 24224879 TI - Triorchidism: two case reports. AB - In this study, two cases of triorchidism are reported. The first case (29 years) had two right discrete ovoid nontender, firm, mobile lumps with testicular sensation. The second case (32 years) had two left discrete ovoid nontender, firm, mobile lumps with normal testicular sensation. They were subjected to the estimation of serum follicle-stimulating hormone, luteinising hormone, free and total testosterone, alpha-fetoprotein, prostate-specific antigen, karyotyping and semen analysis. Imaging included ultrasonography, transrectal ultrasound, magnetic resonance imaging and intravenous pyelography. The first case had two testes in the right side. Each one had an epididymis where one vas deferens was palpated. The second case had two left testes with normal testicular sensation. The lower left lump represented normal-sized testis attached to its epididymis and a single palpated vas deferens. Diagnosis of the first case was triorchidism associated with left varicocele (grade I) with oligoasthenoteratozoospermic semen profile. Intracytoplasmic sperm injection was carried out resulting in a twin. Diagnosis of the second case was triorchidism with accessory testis on the left side associated with left varicocele (grade I) and asthenozoospermic semen profile that was submitted to medical treatment. It is concluded that triorchidism is an uncommon congenital anomaly that should be not overlooked in diagnosing scrotal masses. PMID- 24224880 TI - The influence of physical activity during youth on structural and functional properties of the Achilles tendon. AB - Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon cross-sectional area or tendon free length. There was no difference between the groups with respect to maximal force or mechanical properties. The collagen content, enzymatic and nonenzymatic cross-link density did not differ between the groups, nor did collagen fibril density, diameter, and area. There was a correlation between age and pentosidine/collagen within the groups [(HAY: P < 0.05 and r(2) = 0.47) and (LAY: P < 0.05 and r(2) = 0.52)]. The data suggest that high or low activity during youth did not appreciably influence the mechanical, structural, or biochemical properties of the Achilles tendon in adult long distance runners. PMID- 24224881 TI - Competing frameworks in planning for the aged in the growth corridors of Melbourne. AB - The Ageing in the Growth Corridors Project was initiated as a partnership between the University of Melbourne and the Department of Health in the Northwest Metropolitan Region of Melbourne, Australia. It involved a research team working with six project officers appointed to stimulate development in relation to an aging population in the sprawling outer metropolitan growth corridors. This article identifies the key lessons learned in terms of project implementation relating to attitudinal and structural barriers to the development of an age friendly environment in areas of rapid urban growth. The findings illustrate some of the dilemmas raised by competing program conceptions, a dynamic and changing federal/state policy context, and local resource and strategic management constraints. The partnership with the university, nevertheless, provided a point of stability and continuity for the project officers in implementing their mandate. PMID- 24224882 TI - Maternal dietary counseling during pregnancy and infant fatty acid profiles. AB - We aimed to explore whether maternal dietary counseling to increase the intake of unsaturated fatty acids (FA) is reflected in infant FA status. Serum cholesteryl ester (CE) and triacylglycerol (TAG) FA were analyzed from infants of 45 women randomized to receive dietary counseling from the first trimester of pregnancy and 45 control women. Counseling resulted in a higher intake of polyunsaturated FA and a lower intake of saturated FA. The dietary intake was reflected in cord blood TAGs: the n-6 to n-3 FA ratio was lower [mean difference -0.50 (95%CI -0.95 to -0.06)] and the sum of n-3 FA was higher in the intervention than in the control group [1.46 (0.44 to 2.48)% of total FA]. Reasons for the lack of changes in the cord blood CE fraction and FA fractions at 1-month remain unclear, but may indicate that the changes achieved in the maternal diet through counseling were too modest. PMID- 24224883 TI - Insulin therapy for the treatment of type 1 diabetes during pregnancy. AB - Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient. PMID- 24224884 TI - Exploring functional concerns in help-seeking youth: a qualitative study. AB - AIM: This study aimed to explore the functional concerns of help-seeking young people 12-25 years of age. METHOD: Semistructured interviews with n = 10 young people seeking help from a youth mental health clinic were conducted. Data were transcribed verbatim and analysed using content analysis. Results were verified by member checking. RESULTS: Participants identified reasons for seeking help, with the main themes being relationships, emotional management, risk-taking behaviour and difficulties with employment. There appeared to be a difference between the concerns of the older, post-school-age group and the younger participants. CONCLUSION: Young people are able to identify their functional concerns and reasons for seeking help from mental health services. Understanding the concerns of these young people provides weight to the model of youth-specific mental health services. Future work examining concerns of 12-25 year olds should ensure adequate representation of the older group as their needs and concerns seem to differ from those of younger participants in this study. Post-school-age youth seem to be under-represented in existing literature in this field. However, a limitation with this study is the small sample sizes once the cohort is divided by age. Future studies with a larger, more detailed examination of the needs and concerns of this population are warranted to inform service delivery advancements and clarify the difference in needs between the post-school and current school attendee groups. PMID- 24224885 TI - Factors associated with the development of chronic pain after surgery for breast cancer: a prospective cohort from a tertiary center in the United States. AB - Chronic pain has been shown to affect up to 60% of patients undergoing surgery for breast cancer. Besides younger age, other risk factors for the development of chronic pain have not been consistent in previous studies. The objective of the current investigation was to detect the prevalence and risk factors for the development of chronic pain after breast cancer surgery by examining a patient population from a tertiary cancer center in the United States. The study was a prospective observational cohort study. Subjects were evaluated at least 6 months after the surgical procedure. Subjects responded to the modified short form Brief pain inventory and the short form McGill pain questionnaire to identify and characterize pain. Demographic, surgery, cancer treatment, and perioperative characteristics were recorded. Propensity matching regression analysis were used to examine risk factors associated with the development of chronic pain. 300 patients were included in the study. 110 reported the presence of chronic pain. Subjects with chronic pain reported median (interquartile range [IQR]) rating of worst pain in the last 24 hours of 4 (2-5) and a median (IQR) rating on average pain in the last 24 hours of 3 (1-4) on a 0-10 numeric rating scale. Independent risk factors associated with the development of chronic pain were age, OR (95% CI) of 0.95 (0.93-0.98) and axillary lymph node dissection, 7.7 (4.3-13.9) but not radiation therapy, 1.05(0.56-1.95). After propensity matching for confounding covariates, radiation was still not associated with the development of chronic pain. Chronic pain after mastectomy continues to have a high prevalence in breast cancer patients. Younger age and axillary lymph node dissection but not radiation therapy are risk factors for the development of chronic pain. Preventive strategies to minimize the development of chronic pain are highly desirable. PMID- 24224887 TI - Understanding the microscopic origin of gold nanoparticle anisotropic growth from molecular dynamics simulations. AB - We use molecular dynamics simulations in order to understand the microscopic origin of the asymmetric growth mechanism in gold nanorods. We provide the first atomistic model of different surfaces on gold nanoparticles in a growing electrolyte solution, and we describe the interaction of the metal with the surfactants, namely, cetyltrimethylammonium bromide (CTAB) and the ions. An innovative aspect is the inclusion of the role of the surfactants, which are explicitly modeled. We find that on all the investigated surfaces, namely, (111), (110), and (100), CTAB forms a layer of distorted cylindrical micelles where channels among micelles provide direct ion access to the surface. In particular, we show how AuCl2(-) ions, which are found in the growth solution, can freely diffuse from the bulk solution to the gold surface. We also find that the (111) surface exhibits a higher CTAB packing density and a higher electrostatic potential. Both elements would favor the growth of gold nanoparticles along the (111) direction. These findings are in agreement with the growth mechanisms proposed by the experimental groups of Murphy and Mulvaney. PMID- 24224886 TI - Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa. AB - Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy. PMID- 24224888 TI - Toward sensitive graphene nanoribbon-nanopore devices by preventing electron beam induced damage. AB - Graphene-based nanopore devices are promising candidates for next-generation DNA sequencing. Here we fabricated graphene nanoribbon-nanopore (GNR-NP) sensors for DNA detection. Nanopores with diameters in the range 2-10 nm were formed at the edge or in the center of graphene nanoribbons (GNRs), with widths between 20 and 250 nm and lengths of 600 nm, on 40 nm thick silicon nitride (SiN(x)) membranes. GNR conductance was monitored in situ during electron irradiation-induced nanopore formation inside a transmission electron microscope (TEM) operating at 200 kV. We show that GNR resistance increases linearly with electron dose and that GNR conductance and mobility decrease by a factor of 10 or more when GNRs are imaged at relatively high magnification with a broad beam prior to making a nanopore. By operating the TEM in scanning TEM (STEM) mode, in which the position of the converged electron beam can be controlled with high spatial precision via automated feedback, we were able to prevent electron beam-induced damage and make nanopores in highly conducting GNR sensors. This method minimizes the exposure of the GNRs to the beam before and during nanopore formation. The resulting GNRs with unchanged resistances after nanopore formation can sustain microampere currents at low voltages (~50 mV) in buffered electrolyte solution and exhibit high sensitivity, with a large relative change of resistance upon changes of gate voltage, similar to pristine GNRs without nanopores. PMID- 24224889 TI - Anticoagulant surface coating using composite polysaccharides with embedded heparin-releasing mesoporous silica. AB - Release of heparin from the surface of biomaterials is a feasible and efficient manner for preventing blood coagulation because of the high bioactivity of free heparin and a low application dosage compared to intravenous injection of heparin. Here we report a novel method featuring a blend of heparin-loaded SBA 15, catechol-modified chitosan (CCS), and heparin as a heparin-releasing film. The release of heparin was based on its leakage from heparin-loaded amino functionalized mesoporous silica SBA-15 (SBA-15-NH2), which was controlled by the amino density of the SBA-15-NH2. Heparin-loaded SBA-15-NH2, CCS, and heparin were mixed together, and the mixture was cast onto the surface of a polydopamine modified substrate, forming a heparin-releasing film on the surface of the substrate. The polydopamine acted as an adhesive interlayer that stabilized the film coated on the substrate. The sustained release rates of heparin from the film ranged from 15.8 to 2.1 MUg/cm(2)/h within 8 h. The heparin-releasing film showed low fibrinogen adsorption, platelet adhesion, and hemolysis rate, indicating that it has good blood compatibility. This new approach would be very useful for modifying the surface of versatile blood-contacting biomaterials and ultimately improve their anticoagulation performance. PMID- 24224890 TI - Ethanol plus the Jo2 Fas agonistic antibody-induced liver injury is attenuated in mice with partial ablation of argininosuccinate synthase. AB - BACKGROUND: Argininosuccinate synthase (ASS) is an enzyme shared by the urea cycle and the l-citrulline/nitric oxide (NO.) cycle. ASS is the rate-limiting enzyme in the urea cycle and along with nitric oxide synthase 2 (NOS2), it endows cells with the l-citrulline/NO. salvage pathway to continuously supply l-arginine from l-citrulline for sustained NO. generation. Thus, ASS conditions NO. synthesis by NOS2. Because of the relevance of NOS2 activation for liver injury, we examined the contribution of ASS to NO. generation and how it impacts liver injury. METHODS: Wild-type (WT) mice and Ass(+/-) mice (Ass(-/-) mice are lethal) were intraperitoneally injected with ethanol (EtOH) at a dose of 2.5 g/kg of body weight twice a day for 3 days. Two hours after the last dose of EtOH, mice were administered the agonistic Jo2 anti-mouse Fas monoclonal antibody (Ab) at a dose of 0.2 MUg/g of body weight. Mice were sacrificed 8 hours after the Jo2 Ab injection. Markers of nitrosative and oxidative stress as well as liver damage were analyzed. RESULTS: EtOH plus Jo2 injection induced liver injury as shown by serum alanine aminotransferase and aspartate aminotransferase activity, liver pathology, TUNEL, and cleaved caspase-3 were lower in Ass(+/-) mice compared with WT mice, suggesting that ASS contributes to EtOH plus Jo2-mediated liver injury. CYP2E1 induction, glutathione depletion, and elevated thiobarbituric acid reactive substances were comparable in both groups of mice, suggesting that CYP2E1-mediated oxidative stress is not linked to ASS-induced liver injury. In contrast, NOS2 induction, 3-nitrotyrosine adducts formation and elevated nitrites, nitrates, and S-nitrosothiols were higher in livers from WT mice than from Ass(+/-) mice. CONCLUSION: Decreased nitrosative stress causes lower EtOH plus Jo2-induced liver injury in Ass(+/-) mice. PMID- 24224891 TI - Does the reconstitution of RC-LH1 complexes from Rhodopseudomonas acidophila strain 10050 into a phospholipid bilayer yield the optimum environment for optical spectroscopy? AB - We have investigated reaction-center light-harvesting 1 (RC-LH1) complexes from Rhodopseudomonas (Rps.) acidophila in detergent buffer solution and reconstituted into a phospholipid bilayer and compared the results with the outcome of an earlier study conducted on RC-LH1 immobilized in polyvinyl alcohol (PVA). The aim of this study was to test whether the immobilization of the complexes in a PVA matrix might lead to a deterioration of the proteins and thereby limit the accessible information that can be obtained from optical spectroscopy. It has been found that the complexes dissolved in a detergent buffer solution are subject to fast spectral dynamics preventing any meaningful application of single molecule spectroscopy. In contrast, for the bilayer samples it is revealed that the reconstitution process results in a significantly larger fraction of broken complexes with respect to the preparation of the complexes in a PVA film. Moreover, we find that for the intact complexes the statistics of the key spectral features, such as the spectral separations of the bands and the mutual orientation of their transition-dipole moments, show no variation dependent on using either a bilayer or PVA as a matrix. Given the additional effort involved in the reconstitution process, the lower amount of intact RC-LH1 complexes and, concerning the decisive spectral details, the identical results with respect to embedding the complexes in a PVA matrix, we come to the conclusion that the immobilization of these proteins in a PVA matrix is a good choice for conducting low-temperature experiments on individual light-harvesting complexes. PMID- 24224892 TI - Intrinsic optical activity and conformational flexibility: the role of size dependent ring morphology in model cycloketones. AB - The optical rotatory dispersion of two monocyclic ketones, (R)-3 methylcyclopentanone [R-3MCP] and (R)-3-methylcyclohexanone [R-3MCH], has been investigated under isolated and solvated conditions to explore the role of ring size/morphology and to elucidate the impact of environmental perturbations. Vapor phase measurements of specific rotation, [alpha]lambdaT, were performed at 355/633 nm by means of cavity ring-down polarimetry while complementary solution phase work employed a canonical discrete-wavelength polarimeter to probe five distinct solvents. The magnitude of [alpha]lambdaT was found to increase upon solvation, albeit to different extents for the two species of interest, with the attendant sign switching between the solution and vapor phases for lambda >= 510.7 nm in the case of R-3MCH. Quantum-chemical analyses suggest two low-lying conformers to exist for each ketone, distinguished by an equatorial or axial arrangement of the methyl substituent. Linear-response calculations built upon density-functional [DFT(B3LYP)/aug-cc-pVTZ] and coupled-cluster [CCSD/aug-cc pVDZ] frameworks gave antagonistic chiroptical parameters for these isomers, which were combined with various energy metrics in a conformer-averaging ansatz to simulate the response for a thermally equilibrated ensemble. The intrinsic behavior of R-3MCP was reproduced best by averaging DFT optical-activity predictions according to relative populations deduced from free-energy differences; however, less satisfactory agreement was realized for isolated R 3MCH molecules. The sizable circular birefringence of R-3MCP can be attributed to inherent chirality of its twisted carbon ring whereas the more modest response of R-3MCH stems mainly from the lone stereogenic center. The implicit polarizable continuum model treated solvation effects in R-3MCP with moderate success, but failed to replicate solvent-dependent trends in R-3MCH. The relationship of dispersive optical activity to bulk characteristics of the surrounding medium, including dielectric constant, refractive index, and polarizability, is discussed with the goal of bridging the gap between isolated and solvated chiroptical properties. PMID- 24224893 TI - Maternal input to children with specific language impairment during shared book reading: is mothers' language in tune with their children's production? AB - BACKGROUND: The literature on input addressed to children with specific language impairment (SLI) has shown contrasting results on the role that parents assume during conversational interactions. Some studies have shown that parents compensate for the child's linguistic limitations. In contrast, other studies have indicated that mothers are able to adjust their communication in response to their children's language characteristics. AIMS: To assess the 'closeness of fit' between maternal input and child language profiles in children with SLI during shared book reading. To achieve this aim, the individual linguistic features of a group of children with SLI and their mothers were compared with those of two typically developing (TD) groups and the 'distances' (i.e., the differences between the mother's and her child's linguistic indices) within each dyad were compared. METHOD & PROCEDURES: Three groups of children with their mothers participated in the study: 14 children with expressive SLI, 14 language age matched TD children (LA-matched group), and 14 chronological age-matched TD children (CA-matched group). Each mother-child dyad was videotaped during two weekly sessions of shared book reading, at home. All sessions were entirely transcribed. For each session, the following indices were then considered: whole word phonological indices, grammatical categories and lexical indices for types and tokens, and the distance between the mother's and the child's linguistic indices within individual dyads. OUTCOMES & RESULTS: Analysis of the differences between phonological, lexical and morphosyntactic characteristics of the mothers' and children's language indicated that both children with SLI and their mothers produced adjectives and adverbs with lower phonological complexity and with higher frequency of use compared with the CA-matched group, and nouns with lower frequency of use and higher age of acquisition compared with the LA-matched group. In addition, individual dyads within the SLI group displayed reduced distances between linguistic indices produced by the mother and child compared with dyads within the CA-matched group. CONCLUSIONS & IMPLICATIONS: On the whole these findings suggest that mothers of children with SLI are able to tune their language to their children's linguistic limitations. These findings may contribute to improving early intervention programmes with children with SLI by focusing on the mother-child interaction during shared book reading. PMID- 24224894 TI - Fractal and Euclidean descriptors of platelet shape. AB - Platelet shape change is a dynamic membrane surface process that exhibits remarkable morphological heterogeneity. Once the outline of an irregular shape is identified and segmented from a digital image, several mathematical descriptors can be applied to numerical characterize the irregularity of the shapes surface. 13072 platelet outlines (PLO) were segmented automatically from 1928 microscopic images using a newly developed algorithm for the software product Matlab R2012b. The fractal dimension (FD), circularity, eccentricity, area and perimeter of each PLO were determined. 972 PLO were randomly assigned for computer-assisted manual measurement of platelet diameter as well as number, width and length of filopodia per platelet. FD can be used as a surrogate parameter for determining the roughness of the PLO and circularity can be used as a surrogate to estimate the number and length of filopodia. The relationship between FD and perimeter of the PLO reveals the existence of distinct groups of platelets with significant structural differences which may be caused by platelet activation. This new method allows for the standardized continuous numerical classification of platelet shape and its dynamic change, which is useful for the analysis of altered platelet activity (e.g. inflammatory diseases, contact activation, drug testing). PMID- 24224895 TI - Clinical Factors Influencing Removal of the Cement Excess in Implant-Supported Restorations. AB - BACKGROUND: The depth of the cementation margin has an influence on the amount of cement remnants around implants. However, the role of other clinical factors is still not clarified. PURPOSE: The aim of the study was to evaluate the correlation between undetected cement and (i) location of the implant, (ii) implant diameter, and (iii) undercut. MATERIALS AND METHODS: Sixty-five patients were treated with single metal-ceramic restorations on implants. The undercut between the restoration and the tissue was measured. After cementation, the restoration-abutment unit was unscrewed. All quadrants of the specimens were photographed and analyzed. The ratio between total restoration area/peri-implant tissue area and area of cement remnants was calculated in pixels. Significance was set to 0.05. RESULTS: Sixty-five metal-ceramic restorations were placed on 65 implants (39 molars, 22 premolars, 4 anteriors; 21 implants had a diameter of 3.5 mm, 34 of 4.0 mm, 10 of 5.0 mm). An undercut of 1 mm was found in 118 sites, 2 mm in 96 sites, and 3 mm in 46. The percentages of soft tissue and restoration, respectively, covered by cement were as follows: molars 4% and 7%; premolars 3.8% and 7.3%; anteriors 3% and 3.4%; 3.5 mm diameter 3.3% and 7.4%; 4.0 mm 7.7% and 7.7%; 5.0 mm 3.9% and 2.1%; 1-mm undercut 3.5% and 5.4%; 2-mm 4% and 8.1%; 3-mm 4.8% and 8.4%. The relationship between amount of cement remnants and implant location was insignificant (p > 0.05) for both soft tissue and the specimen, but significant relationships with amount of cement remnants were found for diameter (p = 0.026 for soft tissue, p = 0.600 for specimen) and undercut (p = 0.004 for soft tissue, p = 0.046 for specimen). CONCLUSION: If cemented crown restoration is desired, undercuts should be reduced to a minimum for better removal of cement excess, irrespective of the diameter and location of the implants in the mouth. PMID- 24224896 TI - The highs and lows of caregiving for chronically ill lesbian, gay, and bisexual elders. AB - This study examines informal caregivers' and LGB care recipients' best and worst experiences of care within their relationship. Communal relationship theory guides the research. The work uses qualitative interview data from a sample of 36 care pairs (N = 72), divided between committed partners and friends, to understand the similarities and differences in the care norms employed in varied relationship contexts. Findings from the study show that relationship context influences the experiences that caregivers and care recipients identify as best and worst, but often focus on the relationship and needs met at bests, and conflict and fear of worsening health as worsts. PMID- 24224897 TI - Eosinophil-rich granulomatous panniculitis caused by exenatide injection. PMID- 24224898 TI - Plasmonic nature of the terahertz conductivity peak in single-wall carbon nanotubes. AB - Plasmon resonance is expected to occur in metallic and doped semiconducting carbon nanotubes in the terahertz frequency range, but its convincing identification has so far been elusive. The origin of the terahertz conductivity peak commonly observed for carbon nanotube ensembles remains controversial. Here we present results of optical, terahertz, and direct current (DC) transport measurements on highly enriched metallic and semiconducting nanotube films. A broad and strong terahertz conductivity peak appears in both types of films, whose behaviors are consistent with the plasmon resonance explanation, firmly ruling out other alternative explanations such as absorption due to curvature induced gaps. PMID- 24224899 TI - Analysis of pesticide residues in strawberries and soils by GC-MS/MS, LC-MS/MS and two-dimensional GC-time-of-flight MS comparing organic and integrated pest management farming. AB - This study analysed 22 strawberry and soil samples after their collection over the course of 2 years to compare the residue profiles from organic farming with integrated pest management practices in Portugal. For sample preparation, we used the citrate-buffered version of the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. We applied three different methods for analysis: (1) 27 pesticides were targeted using LC-MS/MS; (2) 143 were targeted using low pressure GC-tandem mass spectrometry (LP-GC-MS/MS); and (3) more than 600 pesticides were screened in a targeted and untargeted approach using comprehensive, two dimensional gas chromatography time-of-flight mass spectrometry (GC * GC-TOF-MS). Comparison was made of the analyses using the different methods for the shared samples. The results were similar, thereby providing satisfactory confirmation of both similarly positive and negative findings. No pesticides were found in the organic-farmed samples. In samples from integrated pest management practices, nine pesticides were determined and confirmed to be present, ranging from 2 ug kg(-1) for fluazifop-p-butyl to 50 ug kg(-1) for fenpropathrin. Concentrations of residues in strawberries were less than European maximum residue limits. PMID- 24224900 TI - Sequencing therapy in advanced prostate cancer: focus on sipuleucel-T. AB - Immunotherapies such as sipuleucel-T present new and unique challenges for the optimal timing and sequencing of therapies for metastatic castration-resistant prostate cancer (mCRPC). Key considerations for the sequencing of sipuleucel-T are its unique proposed mechanism of action, the time required to generate a clinically relevant immune response, and the observed efficacy in Phase III trials in 'early' or asymptomatic or minimally symptomatic mCRPC. There are three broad timing and sequencing options for sipuleucel-T in patients with rising prostate-specific antigen and radiologic evidence of disease: immediately after androgen-deprivation therapy failure, after failure of secondary hormonal maneuvers, or after chemotherapy. There are several other agents in Phase III development in mCRPC and any future approvals will impact on the current treatment algorithm, and raise further questions regarding how to optimize sequencing and timing of therapies for better clinical outcomes. PMID- 24224901 TI - Protective and reparative effects of peptides from soybean beta-conglycinin on mice intestinal mucosa injury. AB - Peptides derived from alcalase digestion of soybean beta-conglycinin, containing 8.52% carbohydrate, exhibits an inhibition effect on pathogen adhesion or translocation to intestinal cells in vitro. In this study, the protective and reparative effects of beta-conglycinin peptides on intestinal mucosa injury in vivo were studied using mice with dextran sulfate sodium (DSS)-induced intestinal mucosa injury. The results showed that beta-conglycinin peptides contained approximately 21.77% glutamic acid (Glu), and significantly reduced the histological injury in mice both in the protective and reparative experiments. The myeloperoxidase activity of mice treated with beta-conglycinin peptides decreased compared with those treated DSS in the positive control group. Immunohistochemical analysis also showed that beta-conglycinin peptides inhibited the expression of inflammatory factor NF-kappaB/p65. These results suggested that peptides derived from soybean beta-conglycinin exhibited protective and reparative effects on mice intestinal mucosa injury. PMID- 24224902 TI - Predictors of nipple ischemia after nipple sparing mastectomy. AB - Nipple sparing mastectomy (NSM) has become an accepted approach in selected cases of breast cancer and prophylactic mastectomy. Various surgical techniques have been described and nipple ischemia has been a common complication. Potential risk factors for nipple ischemia after NSM are examined. To examine predisposing factors for nipple ischemia after NSM. Prospective evaluation of 71 consecutive NSM in 45 patients from 2009 to 2011 was performed. There were 40 mastectomies for cancer (56.3%), and 31 (43.7%) prophylactic mastectomies. In cases of cancer, the ducts were excised from the undersurface of the nipple. Reconstructive methods included: expander 58, latissimus flap/expander 2, implant 10, and free TRAM flap 1. Various patient and technical factors were examined for impact on nipple ischemia. Partial nipple necrosis occurred in 20 cases (28.2%). Nineteen cases healed uneventfully and one required secondary nipple reconstruction. Operations for cancer (OR 10.54, CI 1.88-59.04, p = 0.007) and periareolar incisions (OR 9.69, CI 1.57-59.77, p = 0.014) predisposed to nipple ischemia. Periareolar incisions and dissection of the nipple ducts for cancer have a higher risk of nipple necrosis after NSM. PMID- 24224904 TI - Self-reported symptoms and health service use in adolescence in persons who later develop psychotic disorders: a prospective case-control study. AB - AIM: To investigate self-reported psychiatric and somatic symptoms and health service use at age 16 in persons who later developed a psychotic disorder compared with a control group from the same geographical areas. METHOD: Responses concerning psychiatric or somatic health and health service use from Norwegian youth studies in a cohort of 15- and 16-year-olds in three Norwegian counties (N = 11 101, 90% response rate) were gathered. The questionnaire responses from persons later identified with a lifetime diagnosis of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) psychotic disorders (n = 30) (confirmed psychosis, CP) were compared with responses from the rest of the group (population control, PC) (n = 11 067). Follow-up analyses were made for cases with a confirmed onset of a psychotic disorder after the time of the survey (n = 21). RESULTS: The main significant differences between the CP and PC groups were more self-reported anxiety, depression and 'feeling in need of treatment for eating disorders' at age 16 in the CP group. The rate of self-reported eating disorder symptoms alone reached the level of statistical significance in the follow-up analyses. The CP group did not use available health services to a markedly greater extent than the control group. CONCLUSION: We found that, in comparison with others, youths who were later identified with a psychotic disorder reported more symptoms at age 16. PMID- 24224903 TI - Long-term facilitation of ventilation in humans with chronic spinal cord injury. AB - RATIONALE: Intermittent stimulation of the respiratory system with hypoxia causes persistent increases in respiratory motor output (i.e., long-term facilitation) in animals with spinal cord injury. This paradigm, therefore, has been touted as a potential respiratory rehabilitation strategy. OBJECTIVES: To determine whether acute (daily) exposure to intermittent hypoxia can also evoke long-term facilitation of ventilation after chronic spinal cord injury in humans, and whether repeated daily exposure to intermittent hypoxia enhances the magnitude of this response. METHODS: Eight individuals with incomplete spinal cord injury (>1 yr; cervical [n = 6], thoracic [n = 2]) were exposed to intermittent hypoxia (eight 2-min intervals of 8% oxygen) for 10 days. During all exposures, end-tidal carbon dioxide levels were maintained, on average, 2 mm Hg above resting values. Minute ventilation, tidal volume, and breathing frequency were measured before (baseline), during, and 30 minutes after intermittent hypoxia. Sham protocols consisted of exposure to room air and were administered to a subset of the participants (n = 4). MEASUREMENTS AND MAIN RESULTS: Minute ventilation increased significantly for 30 minutes after acute exposure to intermittent hypoxia (P < 0.001), but not after sham exposure. However, the magnitude of ventilatory long term facilitation was not enhanced over 10 days of intermittent hypoxia exposures. CONCLUSIONS: Ventilatory long-term facilitation can be evoked by brief periods of hypoxia in humans with chronic spinal cord injury. Thus, intermittent hypoxia may represent a strategy for inducing respiratory neuroplasticity after declines in respiratory function that are related to neurological impairment. Clinical trial registered with www.clinicaltrials.gov (NCT01272011). PMID- 24224905 TI - Use of intravenous propofol in the treatment of migraine headache. PMID- 24224906 TI - Yb5Ga2Sb6: a mixed valent and narrow-band gap material in the RE5M2X6 family. AB - A new compound Yb5Ga2Sb6 was synthesized by the metal flux technique as well as high frequency induction heating. Yb5Ga2Sb6 crystallizes in the orthorhombic space group Pbam (no. 55), in the Ba5Al2Bi6 structure type, with a unit cell of a = 7.2769(2) A, b = 22.9102(5) A, c = 4.3984(14) A, and Z = 2. Yb5Ga2Sb6 has an anisotropic structure with infinite anionic double chains (Ga2Sb6)(10-) cross linked by Yb(2+) and Yb(3+) ions. Each single chain is made of corner-sharing GaSb4 tetrahedra. Two such chains are bridged by Sb2 groups to form double chains of 1/infinity [Ga2Sb6(10-)]. The compound satisfies the classical Zintl-Klemm concept and is a narrow band gap semiconductor with an energy gap of around 0.36 eV calculated from the electrical resistivity data corroborating with the experimental absorption studies in the IR region (0.3 eV). Magnetic measurements suggest Yb atoms in Yb5Ga2Sb6 exist in the mixed valent state. Temperature dependent magnetic susceptibility data follows the Curie-Weiss behavior above 100 K and no magnetic ordering was observed down to 2 K. Experiments are accompanied by all electron full-potential linear augmented plane wave (FP-LAPW) calculations based on density functional theory to calculate the electronic structure and density of states. The calculated band structure shows a weak overlap of valence band and conduction band resulting in a pseudo gap in the density of states revealing semimetallic character. PMID- 24224907 TI - An essential enzyme for phospholipid synthesis associates with the Bacillus subtilis divisome. AB - The mechanism by which the membrane synthetic machinery might be co-organized with the cell-division architecture during the bacterial cell cycle remains to be investigated. We characterized a key enzyme of phospholipid and fatty acid synthesis in Bacillus subtilis, the acyl-acyl carrier protein phosphate acyltransferase (PlsX), and identified it as a component of the cell-division machinery. Comprehensive interaction analysis revealed that PlsX interacts with FtsA, the FtsZ-anchoring protein. PlsX mainly localized at the potential division site independent of FtsA and FtsZ and then colocalized with FtsA. By multidirectional approaches, we revealed that the Z-ring stabilizes the association of PlsX at the septum and pole. The localization of PlsX is also affected by the progression of DNA replication. PlsX is needed for cell division and its inactivation leads to aberrant Z-ring formation. We propose that PlsX localization is prior to Z-ring formation in the hierarchy of septum formation events and that PlsX is important for co-ordinating membrane synthesis with cell division in order to properly complete septum formation. PMID- 24224908 TI - FTIR characterization of water-polymer interactions in superacid polymers. AB - The OD stretch of dilute HOD in H2O absorbed in a series of sulfonated syndiotactic poly(styrene) and sulfonated poly(sulfone) membranes was studied using FTIR spectroscopy to measure how the character of the sulfonate head group and the backbone polarity influenced the water-membrane interactions. Using a three-state model, the OD stretch yielded information about the populations of absorbed water participating in hydrogen bonds with polymer-tethered sulfonate groups, water in an intermediate state, or water hydrogen bonding with other water molecules. The perfluoroalkyl sulfonate moiety, which behaves as a superacid, consistently displayed the largest fraction of head-group-associated water due to its strong acidic character. Measurements of the OD stretch gave insight into the strength of the hydrogen bonds formed between water and the sulfonate groups. Water associated with the superacid displayed an OD stretch peak position that was blueshifted by 39 cm(-1) compared to the aryl-sulfonate associated water with an OD stretching frequency that was centered at 2547 cm( 1). The polarity of the polymer backbone also affected the OD stretch peak position. As hydration increased, the OD peak stretching frequency in poly(styrene)-based membranes displayed a red shift from 2566 to 2553 cm(-1), whereas there was no OD peak maxima shift in poly(sulfone)-based membranes due to the greater amount of intermediate water in the more polar poly(sulfone) backbone system. PMID- 24224909 TI - The resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER related caspase-12 activation and PDE activity in vitro. AB - BACKGROUND: Endoplasmic reticulum (ER) stress plays a key role in cell apoptosis pathways. Caspase-12, a proapoptotic gene induced by ER stress, is also the key molecule in ER-related apoptosis. The purpose of this study is to evaluate the protective activity and possible mechanism of resveratrol (ResV) against ethanol (EtOH)-induced apoptosis in human hepatocyte Chang cell line. METHODS: The human hepatocyte Chang cell line was used to test the hypothesis that ResV may alleviate the liver cell apoptosis induced by EtOH. ER stress-inducible proteins and silent mating type information regulation 2 homolog 1 (SIRT1) were assayed by Western blot. Cell viability was studied by MTT assay and apoptosis was measured by Annexin-V and propidium iodide assay. Caspase-12 activation was examined by immunofluorescence staining. Alcohol dehydrogenase-2 (ADH-2) and aldehyde dehydrogenase-2 (ALDH-2) were measured by polymerase chain reaction amplified product length polymorphism. Phosphodiesterase (PDE) activity was assayed in cell lysates using a cyclic nucleotide PDE assay. RESULTS: EtOH exposure significantly increased the expression of ER stress markers and activated signaling pathways associated with ER stress. These include GRP78, p-IRE1alpha, p-eIF2alpha, p-PERK, ATF4 as well as cleaved caspase-3/12, CHOP/GADD153, and Bax in human hepatocyte Chang cell line. The expression of these proteins were significantly down regulated by ResV (10 MUM) in a SIRT1-dependent manner. ResV can inhibit EtOH-, tunicamycin-, thapsigargin-induced caspase-12 activation. ADH-2 and ALDH-2 activities are lower in this cell line. PDE activity increased by EtOH was inhibited by ResV (10 MUM). CONCLUSIONS: The results indicate that (i) EtOH induced activation of caspase-12 could be one of the underlying mechanisms of hepatocyte apoptosis; (ii) EtOH-induced cell apoptosis was alleviated via ResV (10 MUM) by inhibiting ER stress and caspase-12 activation in a SIRT1-dependent manner; and (iii) SIRT1 activated indirectly by ResV (10 MUM) attenuates EtOH induced hepatocyte apoptosis partly through inhibiting PDE activity. PMID- 24224910 TI - Polydopamine as an efficient and robust platform to functionalize carbon fiber for high-performance polymer composites. AB - Carbon fibers (CFs), which exhibit excellent physical performances and low density, suffer from their low surface activity in some application. Herein, based on dopamine chemistry, we proposed an efficient method to functionalize them: through a simple dip-coating procedure, the CFs were inverted from amphiphobic to hydrophilic with deposition of polydopamine film. Furthermore, using polydopamine as a bridge, the hydrophilic functionalized CFs were transformed to be oleophilic after following octadecylamine grafting. To illustrate applications of this functionalization strategy, we added 15 wt % functionalized CFs into polar epoxy and nonpolar poly(ethylene-co-octene), and as a consequence, their tensile strength respectively increase by 70 and 60%, which show greater reinforcing effect than the unmodified ones (35 and 35%). The results of dynamic mechanical analysis and scanning electron microscope observations indicate that this polydopamine-based functionalization route brought about satisfactory improvements in interfacial adhesion between fillers and matrix. Considering that this simple approach is facile and robust enough to allow further specific functionalization to adjust surface properties, these findings may lead to the development of new efficient strategies for surface functionalization of CFs that are of great interest to the industrial field. PMID- 24224911 TI - Folate intake and the risk of upper gastrointestinal cancers: a systematic review and meta-analysis. AB - BACKGROUND AND AIM: There is conflicting evidence on the association between folate intake and the risk of upper gastrointestinal tract cancers. In order to further elucidate this relationship, we performed a systematic review and quantitative meta-analysis of folate intake and the risk of esophageal, gastric, and pancreatic cancer. METHODS: Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched to July 26, 2013, with no language restrictions for observational studies that measured folate intake and the risk of esophageal cancer, gastric cancer, or pancreatic cancer. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model. RESULTS: The meta-analysis of dietary folate and esophageal cancer risk comprising of nine retrospective studies showed a decreased risk of esophageal cancer (odds ratio [OR] 0.59; 95% confidence interval [95% CI] 0.51-0.69). The meta-analysis of dietary folate and gastric cancer risk comprising of 16 studies showed no association (OR 0.94; 95% CI 0.78-1.14). The meta-analysis of dietary folate and pancreatic cancer risk comprising of eight studies showed a decreased risk of pancreatic cancer (OR 0.66; 95% CI 0.49-0.89). CONCLUSION: Dietary folate intake is associated with a decreased risk of esophageal and pancreatic cancer, but not gastric cancer. Interpretation of these relationships is complicated by significant heterogeneity between studies when pooled, and by small numbers of studies available to analyze when stratification is performed to reduce heterogeneity. PMID- 24224912 TI - Acute pain evaluation with Algoplus scale in Cambodian patients. AB - OBJECTIVE: Evaluation of acute pain in patients with language barriers is often difficult during humanitarian missions. Algoplus, a behavioral scale validated for acute pain evaluation in Caucasians with verbal communication difficulties, was tested during a clinical mission in Cambodia in patients admitted to hospital for acute pain. METHODS: Patients (N = 33, 19 men and 14 women [38 +/- 3 years old]) suffering from acute pain were admitted to Calmette Hospital, Phnom Penh, Cambodia during June 2010. Patients spoke Khmer only; a medical trainee who did no speak Khmer performed the Algoplus scale, and a bilingual Khmer pain specialist doctor asked the patient to score pain intensity on a numerical scale (0-10). The relevance of the scale and of each item (facial expression, complaints, look, body position, and atypical behavior yes/no) was studied. Internal consistency was assessed by Cronbach alpha analysis and convergent validity by correlation coefficient. The relationship between Algoplus items and pain intensity was analysed. RESULTS: Pain intensity (6.3 +/- 2.2) and Algoplus scores (2.1 +/- 1.2) are correlated (r = 0.61, P < 0.001): increases in Algoplus are correlated to increases in pain intensity. Internal consistency is 0.51, and scales comparison per item is significant for facial expression (P = 0.028) and complaints (P = 0.005), but not for the other items. CONCLUSION: This feasibility study shows that despite a correlation with pain intensity, Algoplus may underestimate acute pain in this population. It is, however, an interesting tool for future studies to explore facial expression and complaints as proxies of pain in non-communicative patients. PMID- 24224913 TI - Prediction of correlates of daily physical activity in Spanish children aged 8-9 years. AB - The aims of the study were (a) to examine the associations between the daily physical activity (PA) of 8- to 9-year-old children and their parents, and (b) to examine what effect the child's daily PA has on its cardiorespiratory fitness (CRF), body mass index (BMI), and health-related quality of life (HRQoL). The sample consisted of 1021 persons [351 children (8.73 +/- 0.69 years in age) and 670 parents]. Pedometers were used to evaluate PA in parents and their children over the course of 4 days (Thursday-Sunday), with the instructions on how to wear the pedometers for 24 h a day. Also evaluated were height, weight, BMI, CRF (via the maximal multistage 20-m shuttle run test), and HRQoL (via the EQ-5D-Y questionnaire). Associations between these variables were studied using path model techniques. The father's PA predicts his child's daily PA. This in turn predicts the child's lower BMI, CRF, and perceived quality of life. The findings suggest that the role model of a physically active father positively influences the child's PA habits, and hence that the family environment can have an important part to play in promoting health. PMID- 24224915 TI - Water-in-water emulsions based on incompatible polymers and stabilized by triblock copolymers-templated polymersomes. AB - Aqueous solutions containing a mixture of polyethylene glycol (PEG) and dextran homopolymers form an aqueous two-phase system which can be emulsified to give a water-in-water emulsion. We show how these emulsions can be stabilized using triblock polymers containing poly[poly(ethylene glycol) methyl ether methacrylate] (PEGMA), poly (n-butyl methacrylate) (BuMA), and poly[2 (dimethylamino) ethyl methacrylate] (DMAEMA) blocks of general structure Pp-Bb Dd, in which the middle BuMA block is hydrophobic. Low-energy input stirring of mixtures containing equal volumes of PEG- and dex-rich aqueous phases plus 1 wt % of Pp-Bb-Dd stabilizer all form dex-in-PEG emulsions (for the range of Pp-Bb-Dd triblock polymers used here) which have a polymersome-like structure. In favorable cases, the emulsion drop (or templated polymersome) sizes are a few micrometers and are stable for periods in excess of 6 months. The emulsions can be inverted from dex-in-PEG to PEG-in-dex by increasing the volume fraction of dex-rich aqueous phase. We demonstrate that both high and low molecular weight fluorescent solutes "self-load" into either the dex- or PEG-rich regions and that solute mass transfer across the water-water interface occurs on a timescale of less than 1 min. PMID- 24224916 TI - Clinicians' practice environment is associated with a higher likelihood of recommending cesarean deliveries. AB - OBJECTIVE: Little data exist regarding clinicians' role in the rising annual incidence rate of cesarean delivery in the US. We aimed to examine if clinicians' practice environment is associated with recommending cesarean deliveries. STUDY DESIGN: This is a survey study of clinicians who practice obstetrics in the US. This survey included eight clinical vignettes and 27 questions regarding clinicians' practice environment. Chi-square test and multivariable logistic regression were used for statistical comparison. RESULTS: Of 27 675 survey links sent, 3646 clinicians received and opened the survey electronically, and 1555 (43%) participated and 1486 (94%) completed the survey. Clinicians were categorized into three groups based on eight common obstetric vignettes as: more likely (n = 215), average likelihood (n = 1099), and less likely (n = 168) to recommend cesarean. Clinician environment factors associated with a higher likelihood of recommending cesarean included Laborists/Hospitalists practice model (p < 0.001), as-needed anesthesia support (p = 0.003), and rural/suburban practice setting (p < 0.001). CONCLUSION: We identified factors in clinicians' environment associated with their likelihood of recommending cesarean delivery. The decision to recommend cesarean delivery is a complicated one and is likely not solely based on patient factors. PMID- 24224917 TI - 13% efficiency hybrid organic/silicon-nanowire heterojunction solar cell via interface engineering. AB - Interface carrier recombination currently hinders the performance of hybrid organic-silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate 1,1-bis[(di-4 tolylamino)phenyl]cyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics. PMID- 24224918 TI - Preparing the way for doping wurtzite silicon nanowires while retaining the phase. AB - It is demonstrated that boron-doped nanowires have predominantly long-term stable wurtzite phase while the majority of phosphorus-doped ones present diamond phase. A simplified model based on the different solubility of boron and phosphorus in gold is proposed to explain their diverse effectiveness in retaining the wurtzite phase. The wurtzite nanowires present a direct transition at the Gamma point at approximately 1.5 eV while the diamond ones have a predominant emission around 1.1 eV. The aforementioned results are intriguing for innovative solar cell devices. PMID- 24224919 TI - 'I am not a tragedy. I am full of hope': communication impairment narratives in newspapers. AB - BACKGROUND: Individual attitudes and more general attitudes in society can negatively influence the functioning of people with communication disorders according to the World Health Organisation's (WHO) International Classification of Functioning, Disability, and Health (ICF) (2002). Personal narratives have been recommended as the best means to convey and understand a person's life experience and have been investigated extensively. Investigations of personal narratives of communication impairment in mass media continue to be relatively rare in the literature. Published narratives can enrich understandings of clients' experiences by elucidating available representations of lived experiences of communication impairment. AIMS: To answer the following research questions: What types of personal narratives of communication impairments are currently being disseminated in Irish newspapers? How are experiences of communication impairments represented in these narratives? METHODS & PROCEDURES: The study was qualitative, deploying inductive analysis and drawing on Frank's (1995) typology of illness narratives to analyse narratives that were published in two Irish national newspapers over a 12-month period. OUTCOMES & RESULTS: The results illustrate the under-representation of communication impairments in Irish newspapers as ten out of 51 narratives in the corpus pertained to conditions that may have associated communication impairments. None of the narratives related the lived experience of a person with communication impairment in depth. A combination of quest and chaos narrative types was identified in six out of the ten narratives. Three out of the ten narratives featured a combination of chaos and restitution narrative types. One narrative was identified as being entirely a quest narrative. Three narratives contained elements of restitution. Inductive analysis revealed six main themes in the data (two for each narrative type) with one sub-theme identified for each main theme. The six main themes are: positive stances, re-evaluation of life, despair, fear, hope and support of others. CONCLUSIONS & IMPLICATIONS: The under-representation of the lived experience of people with communication impairments in Irish national newspapers may be seen as contributing to a general lack of understanding and awareness of communication impairments. This under-representation, coupled with a lack of awareness, may potentially affect the ability of people with communication impairments to re engage with and reintegrate into their communities. PMID- 24224920 TI - Transfusing neonates based on platelet count vs. platelet mass: a randomized feasibility-pilot study. AB - The objective of this study was to obtain pilot data on which to judge the feasibility and sample size needed for a future comparative-effectiveness trial of platelet transfusions in the NICU. We conducted a limited-scope pilot trial in which neonates were randomized to receive platelet transfusions based on platelet mass vs. platelet count, using preset "transfusion-trigger" values. Analysis included parental consent rate, number of platelet transfusions given, bleeding episodes recorded, and mortality rate. Statistical analysis included ANOVA and Chi-square. A convenience sample of 30 were randomized; 15 per group. No differences were found between groups in gestational age, birth weight, race, gender or clinical diagnoses. The study consent rate was 52% (30/58). No differences were found in number of platelet transfusions received, bleeding episodes, or mortality. Lack of a trend in transfusion-reduction resulted in inability to estimate the number needed in a future comparative-effectiveness trial. Using platelet mass, rather than platelet count, for a NICU platelet transfusion trigger is feasible. However, any future comparative-effectiveness trial, testing the hypothesis that a platelet mass-based trigger reduces the transfusion rate will likely require a very large sample size. PMID- 24224921 TI - Graphene as dispersive solidphase extraction materials for pesticides LC-MS/MS multi-residue analysis in leek, onion and garlic. AB - A multi-residue analytical method was validated for 24 representative pesticides residues in onion, garlic and leek. The method is based on modified QuEChERS sample preparation with a mixture of graphene, primary secondary amine (PSA), and graphitised carbon black (GCB) as reversed-dispersive solid-phase extraction (r DSPE) material and LC-MS/MS. Graphene was first used as an r-DSPE clean-up sorbent in onion, garlic and leek. The results first show that the mixed sorbent of graphene, PSA and GCB has a remarkable ability to clean-up interfering substances in the r-DSPE procedure when compared with the mixture of PSA and GCB. Use of matrix-matched standards provided acceptable results for tested pesticides with overall average recoveries between 70.1% and 109.7% and consistent RSDs <15.6%. In any case, this method still meets the 1-10 MUg kg(-1) detection limit needed for pesticide testing and may be used for qualitative screening applications in which any identified pesticides can be quantified and confirmed by a more intensive method that achieves >70% recovery. PMID- 24224922 TI - Inhibitory effects of sweet cherry anthocyanins on the obesity development in C57BL/6 mice. AB - In the present study, purified sweet cherry anthocyanins (CACN) were evaluated to determine their inhibitory effects on adipocyte differentiation of 3T3-L1 cells and their anti-obesity properties in male C57BL/6 mice fed with high-fat diet (HFD). CACN prevented HFD-induced obesity in C57BL/6 mice. In vivo experiment revealed that 40 and 200 mg/kg of CACN in food reduced the body weight by 5.2% and 11.2%, respectively. CACN supplementation could also reduce the size of adipocytes, leptin secretion, serum glucose, triglyceride, total cholesterol, LDL cholesterol and liver triglycerides. Furthermore, CACN could effectively reduce the expression levels of IL-6 and TNFalpha genes, markedly increase the SOD and GPx activity. Our results indicated that CACN slowed down the development of HFD induced obesity in male C57BL/6 mice. PMID- 24224923 TI - Columnar metaplasia in the esophageal remnant after esophagectomy: a systematic review. AB - Barrett's metaplasia is a well-recognized risk factor for esophageal adenocarcinoma. It is believed to develop in response to the injurious effects of gastroesophageal reflux. Following subtotal esophagectomy and reconstruction with a gastric conduit, many patients experience profound reflux into the remnant esophagus. Barrett's-like epithelium has been described in these patients, and they have been identified as a potential human model in which to study the early events in the development of metaplasia. This phenomenon also raises clinical concerns about the long-term fate of the esophageal remnant following surgery and the potential for further malignant change. This systematic review summarizes the literature on the prevalence and timing of Barrett's metaplasia occurring after esophagectomy, reviews the evidence regarding risk factors and malignant progression in such patients, and considers the implications for clinical practice. PMID- 24224924 TI - Retrospective analysis of the relationship between infantile seborrheic dermatitis and atopic dermatitis. AB - A growing number of dermatologists dispute the existence of infantile seborrheic dermatitis (ISD) as an independent clinical entity. Therefore the aim of the present study was to estimate the epidemiologic features of ISD in a defined population of Greek children, assess its course, and identify associations, if any, with other common dermatoses of childhood. Children from the region of Athens who were examined and diagnosed with typical clinical features of ISD between 1997 and 2011 were included in the study. The relevant data were collected retrospectively from their medical records using a standardized form. Eighty-seven children were enrolled (50 boys, 37 girls; mean age 3.1 mos at the time of ISD diagnosis). The main body areas affected were the scalp and face for the majority of the children (78/87), whereas the trunk and limbs were less frequently involved (9/87). In all cases, erythema and scaling of affected patients were mild to moderate. Forty-nine of the 87 children were followed up over a period of 5 years. Thirty children in this group developed features of atopic dermatitis (AD) at a later stage, according to the UK diagnostic criteria of AD, and 23 of these children were diagnosed with AD, at an average time interval of 6.4 months from ISD onset, and seven presented with clinical features of AD at the time of ISD diagnosis. The remaining 19 children in the follow-up group progressed without developing any other chronic skin disease, and all recovered within 6 months of its onset. Thirty-eight had no further follow-up after their initial ISD diagnosis. In spite of the lack of information on the disease course for the last group, assuming they all recovered, the prevalence of AD (34.4%) in our ISD sample was significantly higher than the prevalence of AD (10.7%) in the general population for the same age group, as shown in a previous study performed in the municipality of Athens (p < 0.001). A significant number of children were found to develop AD shortly after their ISD diagnosis. This finding demonstrates a strong association in the clinical course between the two diseases or indicates that the two diseases may be in the same clinical spectrum. Further epidemiologic studies must be conducted to assess the significance of this finding. PMID- 24224925 TI - The GLT-1 (EAAT2; slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse. AB - Glutamate is the major excitatory neurotransmitter, and is inactivated by cellular uptake catalyzed mostly by the glutamate transporter subtypes GLT-1 (EAAT2) and GLAST (EAAT1). Astrocytes express both GLT-1 and GLAST, while axon terminals in the neocortex only express GLT-1. To evaluate the role of GLT-1 in glutamate homeostasis, we injected GLT-1 knockout (KO) mice and wild-type littermates with [1-(13)C]glucose and [1,2-(13)C]acetate 15 min before euthanization. Metabolite levels were analyzed in extracts from neocortex and cerebellum and (13)C labeling in neocortex. Whereas the cerebellum in GLT-1 deficient mice had normal levels of glutamate, glutamine, and (13)C labeling of metabolites, glutamate level was decreased but labeling from [1-(13)C] glucose was unchanged in the neocortex. The contribution from pyruvate carboxylation toward labeling of these metabolites was unchanged. Labeling from [1,2-(13)C] acetate, originating in astrocytes, was decreased in glutamate and glutamine in the neocortex indicating reduced mitochondrial metabolism in astrocytes. The decreased amount of glutamate in the cortex indicates that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT-1 plays a role in glutamate homeostasis in the cortex. Glutamate is the major excitatory neurotransmitter, and is inactivated by uptake via GLT-1 (EAAT2) and GLAST (EAAT1) transporters, while axon terminals in the neocortex only express GLT-1. To evaluate the role of GLT-1 in glutamate homeostasis, we used [1-(13)C]glucose and [1,2-(13)C]acetate injection and NMR spectroscopy. The results indicate that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT 1 plays a role in glutamate homeostasis in the neocortex. PMID- 24224927 TI - From 3-fold completive self-sorting of a nine-component library to a seven component scalene quadrilateral. AB - Three-fold completive self-sorting of a nine-component library with >=126 possible combinations led to the clean formation of only three heteroleptic metal ligand complexes. Due to the orthogonality of the latter, they were used as corner stones in an integrative self-sorting approach toward a seven-component scalene quadrilateral. PMID- 24224926 TI - Is the efficacy of sorafenib treatment in patients with hepatocellular carcinoma affected by age? AB - Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elderly population that is often quantitatively and qualitatively underrepresented, as a result of the presence of tight enrolment criteria. The aim of this brief review is to highlight the main concerns, pitfalls and warnings regarding the management of HCC in elderly patients, with particular focus on systemic therapy with sorafenib. PMID- 24224928 TI - Control of bond-strain-induced electronic phase transitions in iron perovskites. AB - Unusual electronic phase transitions in the A-site ordered perovskites LnCu3Fe4O12 (Ln: trivalent lanthanide ion) are investigated. All LnCu3Fe4O12 compounds are in identical valence states of Ln(3+)Cu(2+)3Fe(3.75+)4O12 at high temperature. LnCu3Fe4O12 with larger Ln ions (Ln = La, Pr, Nd, Sm, Eu, Gd, Tb) show an intersite charge transfer transition (3Cu(2+) + 4Fe(3.75+) -> 3Cu(3+) + 4Fe(3+)) in which the transition temperature decreases from 360 to 240 K with decreasing Ln ion size. In contrast, LnCu3Fe4O12 with smaller Ln ions (Ln = Dy, Ho, Er, Tm Yb, Lu) transform into a charge-disproportionated (8Fe(3.75+) -> 5Fe(3+) + 3Fe(5+)) and charge-ordered phase below ~250-260 K. The former series exhibits metal-to-insulator, antiferromagnetic, and isostructural volume expansion transitions simultaneously with intersite charge transfer. The latter shows metal-to-semiconductor, ferrimagnetic, and structural phase transitions simultaneously with charge disproportionation. Bond valence calculation reveals that the metal-oxygen bond strains in these compounds are classified into two types: overbonding or compression stress (underbonding or tensile stress) in the Ln-O (Fe-O) bond is dominant in the former series, while the opposite stresses or bond strains are found in the latter. Intersite charge transfer transition temperatures are strongly dependent upon the global instability indices that represent the structural instability calculated from the bond valence sum, whereas the charge disproportionation occurs at almost identical temperatures, regardless of the magnitude of structural instability. These findings provide a new aspect of the structure-property relationship in transition metal oxides and enable precise control of electronic states by bond strains. PMID- 24224929 TI - Amitriptyline versus tizanidine in the management of tension-type headache in Nepal. PMID- 24224930 TI - Development of a satisfaction scale for young people attending youth mental health services. AB - AIMS: This study aimed to develop a comprehensive measurement tool for assessing client satisfaction at a youth mental health service. METHODS: We developed a scale based on existing scale items and by generating new items, before undertaking revisions and item reduction in consultation with an expert panel composed of researchers, clinicians and consumer representatives. This draft scale was then pilot tested in seven enhanced primary care youth mental health services across Australia. RESULTS: A total of 215 respondents completed the scale. Cronbach's alpha (alpha = 0.953) demonstrated excellent internal consistency, and exploratory factor analysis suggested that the scale measures a global construct of satisfaction. CONCLUSIONS: Through a rigorous and participatory process involving key experts, service providers and service users, this study has resulted in the development of a scale that can appropriately measure the level of user satisfaction with youth-friendly early intervention services. PMID- 24224931 TI - The influence of status on group drinking by young adults: a survey of natural drinking groups on their way to and from bars. AB - BACKGROUND: Young people's social standing among friends and peers has been linked to general levels of drinking and has been shown to influence others' drinking. We extend previous research by examining young adults' status within their natural-occurring drinking groups as a predictor of their subsequent alcohol consumption and encouragement of group members' alcohol consumption during a night out at licensed drinking establishments, a salient context for heavy drinking and alcohol-related risk among young adults. METHODS: We recruited same-sex young adult drinking groups (n = 104 groups; 63 all-male; average group size = 3.4 members; Mage = 21.86) on their way to drinking establishments to complete a survey-containing measures of member-nominated within-group status, likeability, and self-reported alcohol consumption-and a breathalyzer test. At the end of the evening, participants completed the same alcohol consumption measures and were asked to nominate group members who encouraged other members to drink that night. RESULTS: Multilevel analysis revealed that higher-status members engaged in the most alcohol consumption (via both self-report and breathalyzer) but in heavier drinking groups only. Higher-status members also encouraged the most alcohol consumed by others, regardless of levels of group drinking. Further, even though being liked by one's peers was positively related to intoxication that night, it did not account for the significant relationship between within-group status and drinking. CONCLUSIONS: Results suggest that peer related prevention programs for young adults' problem drinking may benefit from focusing on the structure and dynamic of young people's drinking groups. Also, programs targeting peer norms may be more successful if they incorporate status related issues. PMID- 24224932 TI - Competitive crystallization of a propylene/ethylene random copolymer filled with a beta-nucleating agent and multi-walled carbon nanotubes. Conventional and ultrafast DSC study. AB - A propylene/ethylene polymeric matrix was reinforced by the simultaneous addition of a beta-nucleating agent (calcium pimelate) and multi-walled carbon nanotubes (MWCNTs) in various concentrations. The present manuscript explores the competitive crystallization tendency that is caused by the presence of the two fillers. On the one hand, calcium pimelate forces the material to crystallize predominantly in the beta-crystalline form, while, on the other, the strong alpha nucleating ability of MWCNTs compels the material to develop higher alpha crystalline content. An in-depth study has been performed on the nanocomposite samples by means of conventional, temperature-modulated, and differential fast scanning calorimetry (DFSC) under various dynamic and isothermal conditions. The results showed that beta-crystals are predominant at low MWCNT content (<2.5 wt %), while, at high MWCNT content, the material crystallizes mainly in the alpha form. The recrystallization phenomenon during melting was confirmed with step scan DSC, and the use of very high cooling rates by UFDSC made it possible to achieve and study the nucleation of the samples. The presence of MWCNTs enabled the nanocomposites to crystallize faster under both isothermal and dynamic conditions. The activation energy of the samples was also calculated according to Friedman's theory. PMID- 24224933 TI - XenoSite: accurately predicting CYP-mediated sites of metabolism with neural networks. AB - Understanding how xenobiotic molecules are metabolized is important because it influences the safety, efficacy, and dose of medicines and how they can be modified to improve these properties. The cytochrome P450s (CYPs) are proteins responsible for metabolizing 90% of drugs on the market, and many computational methods can predict which atomic sites of a molecule--sites of metabolism (SOMs)- are modified during CYP-mediated metabolism. This study improves on prior methods of predicting CYP-mediated SOMs by using new descriptors and machine learning based on neural networks. The new method, XenoSite, is faster to train and more accurate by as much as 4% or 5% for some isozymes. Furthermore, some "incorrect" predictions made by XenoSite were subsequently validated as correct predictions by revaluation of the source literature. Moreover, XenoSite output is interpretable as a probability, which reflects both the confidence of the model that a particular atom is metabolized and the statistical likelihood that its prediction for that atom is correct. PMID- 24224934 TI - Isomers and electronic states of Ni2O2H2 and evaluation of the effect of charge on the electronic properties and reactivity of Ni2O2. AB - Different isomers of Ni2O2H2 are investigated by multireference configuration interaction (MRCI) calculations, based on complete active space self-consistent field (CASSCF) calculations. The lowest-lying Ni2(OH)2 isomer has a rhombic shape with two OH(-) groups bridging two Ni(I) ions. Its ground term is a (1)Ag term. At a relative energy of 1.06 eV, there is a chain-like NiONi(OH2) isomer. A rhombic (NiH)2O2 isomer with Ni-H bonds has a considerably higher energy of 2.93 eV. Both Ni2(OH)2 and NiONi(OH2) feature a large number of low-lying electronic terms that in the case of Ni2(OH)2 form Heisenberg spin ladders due to the coupling of the electrons of two Ni(I) ions (3d(8)4s(1)) with S = 3/2. For the reaction Ni2O2 + H2 -> Ni2(OH)2, the reaction energy is estimated to -2 eV. Finally, neutral and charged Ni2O2 and their hydrogenation products (Ni2O2H2(0/+)) are compared. PMID- 24224935 TI - Native small airways secrete bicarbonate. AB - Since the discovery of Cl(-) impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl(-) transport. However, loss of bicarbonate (HCO3(-)) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3(-) transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3(-) secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3(-) transport in native porcine small airways (~ 1 mm phi). We assayed HCO3(-) transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3(-) plus 125-mM NaGlu Ringer's solution in the presence of luminal amiloride (10 MUM). Under these conditions, because no major transportable anions other than HCO3(-) were present, we took the equivalent short-circuit current to be a direct measure of active HCO3(-) secretion. Applying selective agonists and inhibitors, we show constitutive HCO3(-) secretion in small airways, which can be stimulated significantly by beta-adrenergic- (cAMP) and purinergic (Ca(2+)) -mediated agonists, independently. These results indicate that two separate components for HCO3(-) secretion, likely via CFTR- and calcium-activated chloride channel dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways. PMID- 24224937 TI - Obesity-related inflammation: implications for older adults. AB - The combination of age-related increases in obesity and inflammation can lead to chronic disease, decreased strength, and physical disability. Lifestyle interventions that include moderate caloric restriction along with aerobic and resistance exercise have shown improvements in metabolic outcomes, strength, and physical function in obese older adults. Although few weight loss studies have addressed diet quality, evidence summarized in this review suggests that encouraging intake of antioxidant-rich fruits and vegetables, high-quality protein, low-glycemic index carbohydrates, and omega-3 fatty acids may further ameliorate obesity-related inflammation. Future controlled trials are indicated to examine the effects of incorporating these foods into multimodal weight loss interventions. PMID- 24224936 TI - The Aurora B kinase in Trypanosoma brucei undergoes post-translational modifications and is targeted to various subcellular locations through binding to TbCPC1. AB - The chromosomal passenger complex (CPC) in animals, consisting of Aurora B kinase and three evolutionarily conserved proteins, plays crucial roles in mitosis and cytokinesis. However, Trypanosoma brucei expresses an unusual CPC consisting of an Aurora-like kinase, TbAUK1, and two kinetoplastid-specific proteins, TbCPC1 and TbCPC2. Despite their essential functions, little is known about the regulation of TbAUK1 and the roles of TbCPC1 and TbCPC2. Here, we investigate the effect of post-translational modification on the activity and spatiotemporal control of TbAUK1, and demonstrate that phosphorylation of two conserved threonine residues in the activation loop of the kinase domain contributes to TbAUK1 activation and function. TbAUK1 is SUMOylated in vivo, and mutation of the SUMO-conjugation site compromises TbAUK1 function. Degradation of TbAUK1 requires two destruction boxes and is mediated by the anaphase-promoting complex/cyclosome (APC/C), whereas degradation of TbCPC1 and TbCPC2 is not dependent on the predicted destruction boxes and is APC/C-independent. Moreover, we determine the domains in CPC subunits that mediate the pairwise interactions, and show that disruption of the interaction impairs the localization of TbAUK1 and TbCPC2 but not TbCPC1. Our results demonstrate the requirement of post-translational modifications for TbAUK1 function and a crucial role of TbCPC1 in mediating TbAUK1 localization. PMID- 24224938 TI - Dietary patterns and sarcopenia in an urban African American and White population in the United States. AB - The primary objective of this cross-sectional study was to characterize dietary patterns of African Americans and Whites, 30 to 64 years, examined in the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Other objectives of the study were to evaluate micronutrient adequacy of each pattern and to determine the association of diet with sarcopenia. Cluster analysis was used to determine patterns and mean adequacy ratio (MAR) to determine adequacy of 15 micronutrients. Ten clusters were identified: sandwich, sweet drink, pizza, poultry, frozen meal, dessert, alcoholic drink, bread, starchy vegetables, and pasta/rice dish. MAR ranged from 69 for the sweet drink cluster to 82 for the pasta/rice dish cluster. Sarcopenia was present in 6.4% of the sample, ranging from 1.5% in the poultry cluster to 14.1% in the alcoholic drink cluster. This study is the first to report an association between diet and sarcopenia in people younger than 65 years. The identification of presarcopenia has important implications for dietary interventions that might delay age-associated loss of lean mass. PMID- 24224939 TI - Nutritional risk and 5-year mortality of older community-dwelling Canadian men: the Manitoba Follow-Up Study. AB - This study examines nutritional risk and 5-year mortality rates of community dwelling older Canadian men participating in the Manitoba Follow-Up Study. The surviving cohort (n = 690; mean age = 86.8 years) was mailed a self-administered Nutrition Survey consisting of SCREEN II, a validated nutrition risk screening tool and health-related questions. Five hundred fifty-three completed surveys (80% completion rate) were returned, with 522 (94%) containing complete responses necessary to score nutritional risk, comprising the participants for this analysis. Forty-four percent of the 522 respondents were scored as high risk, 24% at moderate risk, and 32% at low risk. Over five years from 2007 to 2012, 212 (41%) of the men died, with 1-year, 2-year, 3-year, and 4-year survival rates of 92%, 86%, 77%, and 66%, respectively. Men in the lowest 40th percentile of the nutritional risk distribution accounted for half of all deaths. Adjusted for other characteristics, Cox proportional hazard models demonstrated that with each unit decline on the nutritional risk scale there was a 4% greater risk of mortality (hazard ratio = 0.96 [95% CI 0.94,0.98]). Early identification of older men at nutritional risk and timely nutrition interventions are essential in delaying the progression of morbidity and mortality. PMID- 24224940 TI - Nutritional status and related factors in elderly nursing home residents: comparative cross-sectional study in migrants and native Germans. AB - Former guest workers in Germany who stayed on after retirement are now older than 70 years. Nursing homes (NH) are broadening their offer to meet specific requirements of this population. The nutritional status and related problems of the older ethnic minority group living in German NH has so far not been investigated. The aim of this study was, thus, to compare the nutritional situation of older migrants to that of native residents in two "multicultural" NH (cross-sectional study). All residents 65 years and older with a migration background were enrolled and compared to nonmigrants using frequency matching for age and gender. Nutritional status was assessed using body mass index (BMI; cut off for undernourishment: BMI < 22 kg/m(2)) and calf circumference (CC; CC < 31 cm). Care staff completed a questionnaire on residents' health. Consecutive 3-day food records were evaluated to analyze the intake of energy, macro-, and micronutrients. Participants were n = 23 migrants (76 +/- 6 years, 52% female) and n = 37 nonmigrants (78 +/- 7 years, 59% female). Undernourishment was more prevalent in migrants according to BMI (39 vs. 11%; P < 0.05) and CC (57 vs. 22%; P < 0.05). Main nutritional problems in both groups were "loss of appetite" (56 vs. 19%; P < 0.05) and "refusal to eat" (56 vs. 25%; P < 0.05). Energy intake was low (6.4 +/- 1.4, 6.8 +/- 1.6 MJ/d). More than 50% of participants fell below recommended values for vitamin C, B1, B6, D, folate, calcium, and iron; 61% of the migrants had a low vitamin B12 intake. Migrant NH residents were more often undernourished than German NH residents. PMID- 24224941 TI - Construct validation and test-retest reliability of a mealtime satisfaction questionnaire for retirement home residents. AB - Mealtime satisfaction is an important component of quality of life (QOL) in residential care, yet there currently is no self-administered tool described in the literature. The purpose of this study is to investigate internal and test retest reliability, and construct validity of a mealtime satisfaction questionnaire (MSQ) designed for residential care, more specifically retirement homes. A 15-item MSQ was developed and eligible participants from four retirement homes (n = 749) were invited to participate. The participation rate was 24% and the median age was 88 years for respondents. The internal consistency of the MSQ was high (Cronbach Alpha = 0.83) and the test-retest reliability was also high (Intraclass coefficient = 0.91, P < 0.01). The MSQ was associated with a valid and reliable QOL instrument for older adults (Mann Whitney Test = 1595.5, P < 0.01). The MSQ is reliable and is content and construct valid. QOL can be enriched by improving mealtime satisfaction in retirement homes. PMID- 24224943 TI - Coupling physical exercise with dietary glucose supplement for treating cognitive impairment in schizophrenia: a theoretical model and future directions. AB - AIMS: Metabolic dysregulation may disrupt the complex neuroprotective mechanisms essential for brain health. Recent studies have pointed out the possible aetiological role of metabolic dysregulation in the onset of schizophrenia and the associated cognitive impairment. In this paper, we aimed to generate a theoretical model of how a combination of physical exercise and dietary glucose supplement may help to alleviate cognitive impairment in schizophrenia. METHODS: Literature on metabolic dysregulation, especially insulin resistance, in relation to the onset of schizophrenia and the associated cognitive impairment is reviewed. The cognitive enhancement effects of physical exercise and dietary glucose supplement are then summarised. Finally, we propose a theoretical model based on the concerted effects of physical exercise and glucose supplement. RESULTS: In general, the joint action of physical exercise and dietary glucose supplement could up-regulate glucose and insulin transport into the brain, as well as augmenting the release of insulin growth factor-1 and brain-derived neurotrophic factor. Physical exercise and glucose supplement could enhance energy supply and neuroplasticity in brain, subsequently leading to potential cognitive enhancement in schizophrenia. However, glucose supplement is not suitable for patients with abnormal metabolic profile. CONCLUSIONS: The combination of physical exercise and glucose supplement has potential therapeutic values in treating cognitive impairment in schizophrenia. Further research is necessary to investigate the optimal patterns of exercise and doses of glucose for treating cognitive impairment in schizophrenia. PMID- 24224944 TI - Adsorption isotherms and structure of cationic surfactants adsorbed on mineral oxide surfaces prepared by atomic layer deposition. AB - The adsorption isotherms and aggregate structures of adsorbed surfactants on smooth thin-film surfaces of mineral oxides have been studied by optical reflectometry and atomic force microscopy (AFM). Films of the mineral oxides of titania, alumina, hafnia, and zirconia were produced by atomic layer deposition (ALD) with low roughness. We find that the surface strongly influences the admicelle organization on the surface. At high concentrations (2 * cmc) of cetyltrimethylammonium bromide (CTAB), the surfactant aggregates on a titania surface exhibit a flattened admicelle structure with an average repeat distance of 8.0 +/- 1.0 nm whereas aggregates on alumina substrates exhibit a larger admicelle with an average separation distance of 10.5 +/- 1.0 nm. A wormlike admicelle structure with an average separation distance of 7.0 +/- 1.0 nm can be observed on zirconia substrates whereas a bilayered aggregate structure on hafnia substrates was observed. The change in the surface aggregate structure can be related to an increase in the critical packing parameter through a reduction in the effective headgroup area of the surfactant. The templating strength of the surfaces are found to be hafnia > alumina > zirconia > titania. Weakly templating surfaces are expected to have superior biocompatibility. PMID- 24224945 TI - Narrowband ultraviolet B light in Langerhans cell histiocytosis: a case report. AB - Langerhans cell histiocytosis (LCH) (previously called eosinophilic granuloma, Hand-Schuller-Christian syndrome, Letterer-Siwe disease, and Hashimoto-Pritzker disease) is a rare, heterogeneous disorder with highly variable presentation. LCH commonly affects the skin, as well as internal organs. Because the skin lesions appear benign, and LCH is unfamiliar to most physicians, diagnosis is often delayed. Treatment is controversial, with further clinical study needed. For persons with extensive, skin-limited disease, the existing topical therapies are impractical. We present a child with cutaneous LCH lesions that responded to ultraviolet light phototherapy with minimal adverse effects or patient discomfort. PMID- 24224946 TI - Dermatofibroma-associated dystrophic calcification. PMID- 24224947 TI - Pretransplant risk stratification for early survival of renal allograft recipients. AB - BACKGROUND: Baseline comorbidities influence patient outcomes in renal transplantation. Identification of high-risk recipients for patient death and early allograft loss might lead to superior stratification. MATERIAL AND METHODS: In this retrospective study, risk stratification models were developed in a cohort of 392 kidney transplant recipients and validated in an independent cohort to predict short-term (2 year) outcomes. RESULTS: Peripheral arterial disease [OR 7.7 (95% confidence interval (CI): 2.45-24.60); P < 0.001], use of oral anticoagulation [OR 18.68 (95% CI: 3.77-92.46); P < 0.0001], smoking [OR 5.15 (95% CI: 1.67-15.84); P = 0.004], recipient age > 60 years [OR 7.28 (95% CI: 2.33 22.69; P = 0.001)], serum albumin < 40 g/L [OR 5.08 (95% CI: 1.82-14.19); P = 0.002], serum calcium >= 2.42 mM [OR 6.47 (95% CI: 1.37-30.58); P = 0.02] living donation [OR 2.95, (95% CI: 0.31-28.29); P = 0.34)] and previous haemodialysis [OR 3.33, (95% CI: 0.39-28.11); P = 0.27)] were included in the model. The validated model discriminated between low- (< 3 points) and high-risk recipients (> 8.5 points) with mortality rates of 0% vs. 54%. The comparison of the model with the Charlson comorbidity index (CCI) yielded significantly better receiver operating characteristic (ROC) areas (Novel Score ROC: 0.87 vs. CCI: 0.72, P = 0.0012). Early allograft loss was associated with presensitization [OR 3.02 (95% CI: 1.29-7.09); P = 0.011] and presence of hepatitis C antibodies [OR 2.42 (95% CI: 1.09-5.34); P = 0.029]. A risk model (ROC: 0.62) for allograft loss could not be developed. CONCLUSION: Risk stratification based on the novel score might identify high-risk recipients with disproportional risk of early patient death and lead to optimized strategies. PMID- 24224948 TI - Ganglion impar phenol injection in a pediatric patient with refractory cancer pain. PMID- 24224949 TI - The interplay of bottom-up and top-down mechanisms in visual guidance during object naming. AB - An ongoing issue in visual cognition concerns the roles played by low- and high level information in guiding visual attention, with current research remaining inconclusive about the interaction between the two. In this study, we bring fresh evidence into this long-standing debate by investigating visual saliency and contextual congruency during object naming (Experiment 1), a task in which visual processing interacts with language processing. We then compare the results of this experiment to data of a memorization task using the same stimuli (Experiment 2). In Experiment 1, we find that both saliency and congruency influence visual and naming responses and interact with linguistic factors. In particular, incongruent objects are fixated later and less often than congruent ones. However, saliency is a significant predictor of object naming, with salient objects being named earlier in a trial. Furthermore, the saliency and congruency of a named object interact with the lexical frequency of the associated word and mediate the time-course of fixations at naming. In Experiment 2, we find a similar overall pattern in the eye-movement responses, but only the congruency of the target is a significant predictor, with incongruent targets fixated less often than congruent targets. Crucially, this finding contrasts with claims in the literature that incongruent objects are more informative than congruent objects by deviating from scene context and hence need a longer processing. Overall, this study suggests that different sources of information are interactively used to guide visual attention on the targets to be named and raises new questions for existing theories of visual attention. PMID- 24224950 TI - Role of enhanced multi-detector-row computed tomography before urgent endoscopy in acute upper gastrointestinal bleeding. AB - BACKGROUND AND AIM: Multi-detector-row computed tomography (MDCT) has been reported to be a potentially useful modality for detection of the bleeding origin in patients with acute upper massive gastrointestinal (GI) bleeding. The purpose of this study is to investigate the efficacy of MDCT as a routine method for detecting the origin of acute upper GI bleeding prior to urgent endoscopy. METHODS: Five hundred seventy-seven patients with acute upper GI bleeding (514 nonvariceal patients, 63 variceal patients) who underwent urgent upper GI endoscopy were retrospectively analyzed. Patients were divided into three groups: enhanced MDCT, unenhanced MDCT, and no MDCT before endoscopy. The diagnostic accuracy of MDCT for detection of the bleeding origin was evaluated, and the average procedure times needed to endoscopically identify the bleeding origin were compared between groups. RESULTS: Diagnostic accuracy among endoscopists was 55.3% and 14.7% for the enhanced MDCT and unenhanced MDCT groups, respectively. Among nonvariceal patients, accuracy was 50.2% in the enhanced MDCT group, which was significantly better than that in the unenhanced MDCT group (16.5%). In variceal patients, accuracy was significantly better in the enhanced MDCT group (96.4%) than in the unenhanced MDCT group (0.0%). These accuracies were similar to those achieved by expert radiologists. The average procedure time to endoscopic detection of the bleeding origin in the enhanced MDCT group was significantly faster than that in the unenhanced MDCT and no-MDCT groups. CONCLUSIONS: Enhanced MDCT preceding urgent endoscopy may be an effective modality for the detection of bleeding origin in patients with acute upper GI bleeding. PMID- 24224951 TI - Valley carrier dynamics in monolayer molybdenum disulfide from helicity-resolved ultrafast pump-probe spectroscopy. AB - We investigate the valley-related carrier dynamics in monolayer molybdenum disulfide using helicity-resolved nondegenerate ultrafast pump-probe spectroscopy at the vicinity of the high-symmetry K point under the temperature down to 78 K. Monolayer molybdenum disulfide shows remarkable transient reflection signals, in stark contrast to bilayer and bulk molybdenum disulfide due to the enhancement of many-body effect at reduced dimensionality. The helicity-resolved ultrafast time resolved result shows that the valley polarization is preserved for only several picoseconds before the scattering process makes it undistinguishable. We suggest that the dynamical degradation of valley polarization is attributable primarily to the exciton trapping by defect states in the exfoliated molybdenum disulfide samples. Our experiment and a tight-binding model analysis also show that the perfect valley circular dichroism selectivity is fairly robust against disorder at the K point but quickly decays from the high-symmetry point in the momentum space in the presence of disorder. PMID- 24224952 TI - Exposure to an atomic bomb explosion is a risk factor for in-hospital death after esophagectomy to treat esophageal cancer. AB - Esophagectomy, one of the most invasive of all gastrointestinal operations, is associated with a high frequency of postoperative complications and in-hospital mortality. The purpose of the present study was to determine whether exposure to the atomic bomb explosion at Hiroshima in 1945 might be a preoperative risk factor for in-hospital mortality after esophagectomy in esophageal cancer patients. We thus reviewed the outcomes of esophagectomy in 31 atomic bomb survivors with esophageal cancer and 96 controls (also with cancer but without atomic bomb exposure). We compared the incidences of postoperative complications and in-hospital mortality. Of the clinicopathological features studied, mean patient age was significantly higher in atomic bomb survivors than in controls. Of the postoperative complications noted, atomic bomb survivors experienced a longer mean period of endotracheal intubation and higher incidences of severe pulmonary complications, severe anastomotic leakage, and surgical site infection. The factors associated with in-hospital mortality were exposure to the atomic bomb explosion, pulmonary comorbidities, and electrocardiographic abnormalities. Multivariate analysis revealed that exposure to the atomic bomb explosion was an independent significant preoperative risk factor for in-hospital mortality. Exposure to the atomic bomb explosion is thus a preoperative risk factor for in hospital death after esophagectomy to treat esophageal cancer. PMID- 24224953 TI - Acceptance of disability and its predictors among stroke patients in Taiwan. AB - BACKGROUND: Modern medicine has increased the survival rate for stroke patients; however, the patient's psychosocial adaptation after stroke onset may be related to the clinical outcomes. This study aimed to investigate patients' acceptance of disability (AOD) and its predictors in stroke patients. METHODS: This cross sectional study used a purposive sampling method to recruit 175 stroke patients from a hospital in southern Taiwan. A structured questionnaire gathered data on respondent demographics and disease characteristics, and included the Chinese version of the AOD Scale-Revised. Factors associated with AOD were examined by a multiple linear regression analysis. RESULTS: The mean AOD score was 71.72, which indicated a lower level of disease acceptance (range, 32-128). Our findings showed that patients who reported no religious beliefs, shorter disease duration, recurrent stroke episodes, and poorer physical functioning also reported lower levels of disability acceptance. These factors accounted for 38.2% of the variance in AOD among participants. CONCLUSIONS: The findings are beneficial to healthcare providers by identifying those stroke patients with predisposition of having lower disability acceptance, which could then facilitate the provision of appropriate rehabilitation interventions within six months after the diagnosis of stroke to support their adaptation process. PMID- 24224954 TI - S-adenosylhomocysteine inhibits NF-kappaB-mediated gene expression in hepatocytes and confers sensitivity to TNF cytotoxicity. AB - BACKGROUND: Chronic alcohol exposure results in liver injury that is driven in part by inflammatory cytokines such as tumor necrosis factor-alpha (TNF). Hepatocytes are normally resistant to the cytotoxic effects of TNF, but they become sensitized to TNF by chronic alcohol exposure. Recently, we reported that the decrease in the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) that occurs with alcoholic liver injury renders hepatocytes sensitive to TNF cytotoxicity. The purpose of this study was to determine whether inhibition of the transcription factor nuclear factor-kappaB (NF-kappaB) contributed to TNF induced cell death in hepatocytes with high levels of SAH. METHODS: Primary human hepatocytes or HepG2 cells were pre-incubated with a combination of adenosine plus homocysteine to increase SAH levels. Following exposure to TNF, viability was determined by the MTT assay, and activation of the NF-kappaB pathway was assessed by measuring degradation of cytosolic IkappaB-alpha, phosphorylation and translocation of NF-kappaB to the nucleus, and expression of NF-kappaB-dependent genes. TNF-induced apoptotic signaling pathways were assessed by monitoring levels of the anti-apoptotic protein, A20, and cleavage products of the caspase-8 substrate, RIP1. RESULTS: NF-kappaB-mediated gene expression was inhibited in cells with high SAH, despite the fact that TNF-induced degradation of the cytoplasmic inhibitor IkappaB-alpha and accumulation of NF-kappaB in the nucleus persisted for much longer. In contrast to control cells, the NF-kappaB that accumulated in the nucleus of cells with high SAH levels was not phosphorylated at serine 536, a modification associated with activation of the transactivation potential of this transcription factor. The inhibition of transactivation by NF kappaB resulted in lower mRNA and protein levels of the anti-apoptotic protein A20 and increased cleavage of RIP1. CONCLUSIONS: High SAH levels inhibited NF kappaB-mediated gene expression and sensitized primary hepatocytes and HepG2 cells to the cytotoxic effects of TNF. It is likely that crosstalk with other transcription factors is perturbed under these conditions, resulting in still other changes in gene expression. PMID- 24224956 TI - Combining axial and radial nanowire heterostructures: radial Esaki diodes and tunnel field-effect transistors. AB - The ever-growing demand on high-performance electronics has generated transistors with very impressive figures of merit (Radosavljevic et al., IEEE Int. Devices Meeting 2009, 1-4 and Cho et al., IEEE Int. Devices Meeting 2011, 15.1.1-15.1.4). The continued scaling of the supply voltage of field-effect transistors, such as tunnel field-effect transistors (TFETs), requires the implementation of advanced transistor architectures including FinFETs and nanowire devices. Moreover, integration of novel materials with high electron mobilities, such as III-V semiconductors and graphene, are also being considered to further enhance the device properties (del Alamo, Nature 2011, 479, 317-323, and Liao et al., Nature 2010, 467, 305-308). In nanowire devices, boosting the drive current at a fixed supply voltage or maintaining a constant drive current at a reduced supply voltage may be achieved by increasing the cross-sectional area of a device, however at the cost of deteriorated electrostatics. A gate-all-around nanowire device architecture is the most favorable electrostatic configuration to suppress short channel effects; however, the arrangement of arrays of parallel vertical nanowires to address the drive current predicament will require additional chip area. The use of a core-shell nanowire with a radial heterojunction in a transistor architecture provides an attractive means to address the drive current issue without compromising neither chip area nor device electrostatics. In addition to design advantages of a radial transistor architecture, we in this work illustrate the benefit in terms of drive current per unit chip area and compare the experimental data for axial GaSb/InAs Esaki diodes and TFETs to their radial counterparts and normalize the electrical data to the largest cross sectional area of the nanowire, i.e. the occupied chip area, assuming a vertical device geometry. Our data on lateral devices show that radial Esaki diodes deliver almost 7 times higher peak current, Jpeak = 2310 kA/cm(2), than the maximum peak current of axial GaSb/InAs(Sb) Esaki diodes per unit chip area. The radial TFETs also deliver high peak current densities Jpeak = 1210 kA/cm(2), while their axial counterparts at most carry Jpeak = 77 kA/cm(2), normalized to the largest cross-sectional area of the nanowire. PMID- 24224955 TI - Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis). AB - BACKGROUND: Advances in DNA sequencing and proteomics have facilitated quantitative comparisons of snake venom composition. Most studies have employed one approach or the other. Here, both Illumina cDNA sequencing and LC/MS were used to compare the transcriptomes and proteomes of two pit vipers, Protobothrops flavoviridis and Ovophis okinavensis, which differ greatly in their biology. RESULTS: Sequencing of venom gland cDNA produced 104,830 transcripts. The Protobothrops transcriptome contained transcripts for 103 venom-related proteins, while the Ovophis transcriptome contained 95. In both, transcript abundances spanned six orders of magnitude. Mass spectrometry identified peptides from 100% of transcripts that occurred at higher than contaminant (e.g. human keratin) levels, including a number of proteins never before sequenced from snakes. These transcriptomes reveal fundamentally different envenomation strategies. Adult Protobothrops venom promotes hemorrhage, hypotension, incoagulable blood, and prey digestion, consistent with mammalian predation. Ovophis venom composition is less readily interpreted, owing to insufficient pharmacological data for venom serine and metalloproteases, which comprise more than 97.3% of Ovophis transcripts, but only 38.0% of Protobothrops transcripts. Ovophis venom apparently represents a hybrid strategy optimized for frogs and small mammals. CONCLUSIONS: This study illustrates the power of cDNA sequencing combined with MS profiling. The former quantifies transcript composition, allowing detection of novel proteins, but cannot indicate which proteins are actually secreted, as does MS. We show, for the first time, that transcript and peptide abundances are correlated. This means that MS can be used for quantitative, non-invasive venom profiling, which will be beneficial for studies of endangered species. PMID- 24224957 TI - Sybil--efficient constraint-based modelling in R. AB - BACKGROUND: Constraint-based analyses of metabolic networks are widely used to simulate the properties of genome-scale metabolic networks. Publicly available implementations tend to be slow, impeding large scale analyses such as the genome wide computation of pairwise gene knock-outs, or the automated search for model improvements. Furthermore, available implementations cannot easily be extended or adapted by users. RESULTS: Here, we present sybil, an open source software library for constraint-based analyses in R; R is a free, platform-independent environment for statistical computing and graphics that is widely used in bioinformatics. Among other functions, sybil currently provides efficient methods for flux-balance analysis (FBA), MOMA, and ROOM that are about ten times faster than previous implementations when calculating the effect of whole-genome single gene deletions in silico on a complete E. coli metabolic model. CONCLUSIONS: Due to the object-oriented architecture of sybil, users can easily build analysis pipelines in R or even implement their own constraint-based algorithms. Based on its highly efficient communication with different mathematical optimisation programs, sybil facilitates the exploration of high-dimensional optimisation problems on small time scales. Sybil and all its dependencies are open source. Sybil and its documentation are available for download from the comprehensive R archive network (CRAN). PMID- 24224959 TI - Association among oral health parameters, periodontitis, and its treatment and mortality in patients undergoing hemodialysis. AB - BACKGROUND: Chronic periodontitis (CP) is a continuous, reversible source of inflammation with a potential impact on mortality in patients undergoing hemodialysis (HD). This study investigates the impact of oral health indicators, CP, and its treatment on survival rates in a group of patients undergoing HD. METHODS: Clinically stable patients undergoing HD were referred for a dental examination. All patients were prospectively followed in the dialysis clinic, and all-cause mortality was recorded. Three groups of patients were analyzed: those who received CP treatment, those who did not, and patients without CP as a control group. RESULTS: A total of 122 patients (79 males and 43 females, aged 23 to 77 years; mean age: 50 years; range: 23 to 77 years) were enrolled. Forty percent reported having rarely been evaluated by a dentist, and 59% had CP. There were 34 fatal events during a mean follow-up time of 64.1 +/- 11.2 months. Oral factors associated with death in the univariate analysis were decreased frequency of dental visits; non-use of dental floss; increased decayed, missing, and filled teeth index; presence of CP; and absence of CP treatment. Patients with CP had a higher risk of death from all causes compared with patients without CP in the univariate analysis for untreated patients (hazard ratio 2.65 [95% confidence interval 1.06 to 6.59]; P = 0.036) and to a lesser extent for treated patients (2.36 [1.01 to 5.59]; P = 0.047). These significant differences were not maintained after adjustments for confounders in the multivariate model. CONCLUSIONS: These results suggest that poor oral health, including CP, is a common finding in patients undergoing HD. The results of this study call for intervention trials to test the hypothesis that treatment of CP improves survival in maintenance of patients undergoing HD. PMID- 24224958 TI - Involvement of NT3 and P75(NTR) in photoreceptor degeneration following selective Muller cell ablation. AB - BACKGROUND: Neurotrophins can regulate opposing functions that result in cell survival or apoptosis, depending on which form of the protein is secreted and which receptor and signaling pathway is activated. We have recently developed a transgenic model in which inducible and patchy Muller cell ablation leads to photoreceptor degeneration. This study aimed to examine the roles of mature neurotrophin-3 (NT3), pro-NT3 and p75 neurotrophin receptor (P75(NTR)) in photoreceptor degeneration in this model. METHODS: Transgenic mice received tamoxifen to induce Muller cell ablation. Changes in the status of Muller and microglia cells as well as expression of mature NT3, pro-NT3 and P75(NTR) were examined by immunohistochemistry and Western blot analysis. Recombinant mature NT3 and an antibody neutralizing 75(NTR) were injected intravitreally 3 and 6 days after Muller cell ablation to examine their effects on photoreceptor degeneration and microglial activation. RESULTS: We found that patchy loss of Muller cells was associated with activation of surviving Muller cells and microglial cells, concurrently with reduced expression of mature NT3 and upregulation of pro-NT3 and P75(NTR). Intravitreal injection of mature NT3 and a neutralizing antibody to P75NTR, either alone or in combination, attenuated photoreceptor degeneration and the beneficial effect was associated with inhibition of microglial activation. CONCLUSIONS: Our data suggest that Muller cell ablation alters the balance between the protective and deleterious effects of mature NT3 and pro-NT3. Modulation of the neuroprotective action of mature NT3 and pro-apoptotic pro-NT3/P75(NTR) signaling may represent a novel pharmacological strategy for photoreceptor protection in retinal disease. PMID- 24224960 TI - Reliability of partial-mouth recording systems to determine periodontal status: a pilot study in an adult Portuguese population. AB - BACKGROUND: The efficacy of various partial-mouth recording (PMR) systems is analyzed in the evaluation of periodontal status, using index teeth and different combinations of quadrants. METHODS: The study group was formed of 108 adults aged 25 to 65 years old. A full-mouth examination (FME) was performed in all participants to determine the periodontal probing depth (PD) and clinical attachment level (CAL) at six sites per tooth. The results of PMR using the Ramfjord teeth, the Community Periodontal Index of Treatment Needs teeth, and the four quadrants individually and combined in pairs were compared to the results obtained with FME. RESULTS: Concordance with FME in terms of the prevalence of patients with PD >=4 mm, CAL >=2 mm, and CAL >=4 mm was lowest with examination of single quadrants and highest with combinations that included one superior and one inferior quadrant. CONCLUSIONS: PMR systems, particularly with combinations of a superior plus an inferior quadrant, could be useful to evaluate periodontal status based on PD and CAL. This tool could be useful for epidemiologic surveys on periodontal status. PMID- 24224961 TI - Does periodontal infection have an effect on severe asthma in adults? AB - BACKGROUND: The effect of periodontal infection on systemic diseases and conditions has been the subject of numerous studies worldwide. It is considered that periodontitis may influence the hyperinflammatory response in patients with severe asthma as a result of immuno-inflammatory changes. This study aims to evaluate the influence of periodontitis on severe asthma in adults. METHODS: A case-control study was carried out, comprising 220 adult individuals: 113 diagnosed with asthma (case group) and 107 without asthma diagnosis (control group). The diagnosis of periodontitis was established after a full clinical examination using probing depth, clinical attachment level, and bleeding on probing. The diagnosis of severe asthma was based on the criteria recommended by the Global Initiative of Asthma (2012). Descriptive analyses of the variables were performed, followed by bivariate analyses, using the chi(2) test. Association measurements (odds ratio [OR]), with and without adjustment for potential confounders, were obtained. A significance level of 5% was used. RESULTS: The ORunadjusted for the main association was 4.38 (95% confidence interval [CI] = 2.47 to 7.75). In the logistic regression model, after adjusting for age, education level, osteoporosis, smoking habit, and body mass index, the ORadjusted was 4.82 (95% CI = 2.66 to 8.76), which was statistically significant. Individuals with periodontal infection showed, approximately, five times more likelihood to have bronchial inflammation than those without such periodontal tissue infection. CONCLUSION: The findings demonstrate the influence of periodontitis on severe asthma, given that the frequency of periodontitis is higher in individuals with severe asthma than in those without a diagnosis of bronchial inflammation. PMID- 24224962 TI - Evaluation of systemic levels of neutrophilic enzymes in patients with hypertension and chronic periodontitis. AB - BACKGROUND: Inflammation stimulates neutrophils to release their enzymes into the extracellular matrix. The aim of the present study is to investigate the serum levels of matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of MMP (TIMP) 1, myeloperoxidase (MPO), and neutrophil elastase (NE) in patients with hypertension and chronic periodontitis (CP). METHODS: A total of 95 patients were included in the study. Patients were categorized into three groups: healthy control (n = 29), hypertensive control (n = 32), and hypertensive CP (n = 34). Periodontal parameters were recorded, and serum samples were collected from each participant. Serum MMP-8, MMP-9, TIMP-1, MPO, and NE levels in circulation were assessed by enzyme-linked immunosorbent assay. RESULTS: The hypertensive CP group had significantly higher serum MMP-8, MMP-9, and NE levels than the healthy control group (P <0.05). All study groups had similar serum TIMP-1 levels (P >0.05). Significantly higher serum MPO levels were detected in patients with hypertension and CP than healthy controls and hypertensive controls (P <0.05); however, the difference in serum MPO levels was not significant between the healthy controls and hypertensive controls (P >0.05). There was no significant difference in MMP-8/TIMP-1 ratio among the study groups (P >0.05). MMP-9/TIMP-1 ratio was significantly higher in patients with hypertension and CP than healthy controls (P <0.05). CONCLUSIONS: The presence of hypertension along with CP has a considerable effect on serum neutrophilic enzyme levels, except TIMP-1. However, the levels of these enzymes do not seem to be affected by the presence of hypertension only. Further studies including patients who have only CP might help illuminate the effect of CP on these enzymes in patients with hypertension. PMID- 24224963 TI - Declining transition rates to psychosis: the contribution of potential changes in referral pathways to an ultra-high-risk service. AB - AIM: On the basis of applying 'ultra-high-risk' (UHR) criteria, initially high rates of transition to psychosis were reported. However, a decline in transition to psychosis has been observed in recent years. The current descriptive paper aims to investigate if this drop in transition rate may be due to potential changes in patterns of referral to a large UHR clinic. METHODS: One hundred fifty young people who were referred to the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne, Australia, between August 2000 and July 2004 were included. Their referral pathways were assessed using a semistructured interview. Results were compared with a similar study of a cohort referred to the same clinic between 1995 and 1996. RESULTS: The mean number of contacts prior to referral to the PACE Clinic was 1.93 (standard deviation (SD) = 1.15), and the average time between symptom onset and referral to PACE was 46.5 weeks (SD = 57.4). In comparison with the earlier cohort (mean = 2.36; SD = 1.32), our results indicate a lower number of contacts (Cohen's d = 0.35, r = 0.17). Furthermore, participants in the current study were referred twice as fast to the PACE Clinic. CONCLUSIONS: Increasing awareness of UHR symptoms among professionals and in the general population seems to have resulted in faster referral of young people to specialized mental health services. The global drop in transition rate might be due to a change in referral pathways to UHR services. PMID- 24224964 TI - Automatic analysis of selected choroidal diseases in OCT images of the eye fundus. AB - INTRODUCTION: This paper describes a method for automatic analysis of the choroid in OCT images of the eye fundus in ophthalmology. The problem of vascular lesions occurs e.g. in a large population of patients having diabetes or macular degeneration. Their correct diagnosis and quantitative assessment of the treatment progress are a critical part of the eye fundus diagnosis. MATERIAL AND METHOD: The study analysed about 1'000 OCT images acquired using SOCT Copernicus (Optopol Tech. SA, Zawiercie, Poland). The proposed algorithm for image analysis enabled to analyse the texture of the choroid portion located beneath the RPE (Retinal Pigment Epithelium) layer. The analysis was performed using the profiled algorithm based on morphological analysis and texture analysis and a classifier in the form of decision trees. RESULTS: The location of the centres of gravity of individual objects present in the image beneath the RPE layer proved to be important in the evaluation of different types of images. In addition, the value of the standard deviation and the number of objects in a scene were equally important. These features enabled classification of three different forms of the choroid that were related to retinal pathology: diabetic edema (the classification gave accuracy ACC1 = 0.73), ischemia of the inner retinal layers (ACC2 = 0.83) and scarring fibro vascular tissue (ACC3 = 0.69). For the cut decision tree the results were as follows: ACC1 = 0.76, ACC2 = 0.81, ACC3 = 0.68. CONCLUSIONS: The created decision tree enabled to obtain satisfactory results of the classification of three types of choroidal imaging. In addition, it was shown that for the assumed characteristics and the developed classifier, the location of B-scan does not significantly affect the results. The image analysis method for texture analysis presented in the paper confirmed its usefulness in choroid imaging. Currently the application is further studied in the Clinical Department of Ophthalmology in the District Railway Hospital in Katowice, Medical University of Silesia, Poland. PMID- 24224965 TI - Role of glucagon in treating diabetes: evidence and concepts. PMID- 24224967 TI - Six keys for making orthodontics a sustainable dental specialty. PMID- 24224966 TI - A comparative systems analysis of polysaccharide-elicited responses in Neurospora crassa reveals carbon source-specific cellular adaptations. AB - Filamentous fungi are powerful producers of hydrolytic enzymes for the deconstruction of plant cell wall polysaccharides. However, the central question of how these sugars are perceived in the context of the complex cell wall matrix remains largely elusive. To address this question in a systematic fashion we performed an extensive comparative systems analysis of how the model filamentous fungus Neurospora crassa responds to the three main cell wall polysaccharides: pectin, hemicellulose and cellulose. We found the pectic response to be largely independent of the cellulolytic one with some overlap to hemicellulose, and in its extent surprisingly high, suggesting advantages for the fungus beyond being a mere carbon source. Our approach furthermore allowed us to identify carbon source specific adaptations, such as the induction of the unfolded protein response on cellulose, and a commonly induced set of 29 genes likely involved in carbon scouting. Moreover, by hierarchical clustering we generated a coexpression matrix useful for the discovery of new components involved in polysaccharide utilization. This is exemplified by the identification of lat-1, which we demonstrate to encode for the physiologically relevant arabinose transporter in Neurospora. The analyses presented here are an important step towards understanding fungal degradation processes of complex biomass. PMID- 24224968 TI - Re: Labio-lingual root control of lower anterior teeth and canines obtained by active and passive self-ligating brackets. Paolo M. Cattaneo; Raaid A. Salih; Birte Melsen; The Angle Orthodontist, 2013;83(4)691-697. PMID- 24224969 TI - Re: Response to: Labio-lingual root control of lower anterior teeth and canines obtained by active and passive self-ligating brackets. Paolo M. Cattaneo; Raaid A. Salih; Birte Melsen; The Angle Orthodontist, 2013;83(4)691-697. PMID- 24224971 TI - Assessments of nursing home guidelines for quality of care provided to residents with multiple sclerosis. AB - This study assessed the opinions of nursing directors about quality guidelines developed by the National Multiple Sclerosis Society (NMSS) to assist with the care of nursing home residents with multiple sclerosis (MS). Data were collected in a survey of nursing directors at 800 nursing facilities, with 64 nursing directors participating (8.2% response rate). Participating nursing facilities are similar to other nursing homes for facility characteristics and the number of MS residents receiving care. Large majorities of participants thought these NMSS guidelines were important to the development of care plans and staff training. However, most nursing directors were unaware of these guidelines. PMID- 24224972 TI - Experiences of participation in a Swedish society among adults with cerebral palsy or spina bifida: involvement and challenges. AB - Participation in society is vital to mental health and is beneficial to individuals and society. The goal of this study was to provide insight into how people with cerebral palsy and spina bifida view their experiences of participation and to examine factors that might influence this issue. The results show that participants emphasized the importance of being accepted and treated equally. Living independently and being able to play an active and leading role in their lives was also essential. Participation was described as a process of interaction between a person and society, with mutual responsibility in respect to integration. PMID- 24224973 TI - A holistic view in psychiatric rehabilitation: the effects of structure in psychiatric institutions. AB - Achieving independence in society following hospitalization is difficult for people with mental illness. Using quantitative and qualitative research methods, this study examines rehabilitation procedures and identifies possible deficiencies. Patients (n = 150) and employees (n = 50) were invited to participate. The results show little coordination among professionals, patients, and programs. Employees generally believe rehabilitation is more beneficial than do users. Better results could possibly be achieved if the interactional model was used along with the medical model. The findings emphasize the validity of giving patients voices that can lead to better rehabilitation and quality of life. PMID- 24224974 TI - Comparing travel training innovations in Hong Kong and the United States. AB - Transportation services involving travel training provide 1 means of improving the community inclusion of persons with disabilities. Looking at 2 distinct situations, Hong Kong and the United States, this study made inquiries about the properties of the differing systems in place to improve this inclusiveness. Patterns can be identified concerning their approaches for increasing the use of fixed route transportation systems, but each had differences concerning enabling legislation, scope, and funding mechanisms. We provide generalizable suggestions for increasing the use of fixed route transportation. PMID- 24224976 TI - A case of meningitis due to varicella zoster virus reactivation in an immunocompetent child. AB - BACKGROUND: The development of neurological complications due to varicella zoster virus (VZV) reactivation is relatively uncommon, particularly in the case of immunocompetent patients. Only a few cases have been described in the literature, most of which involved adult or elderly patients. CLINICAL PRESENTATION: Two days after his pediatrician had diagnosed herpes zoster and prescribed oral acyclovir 400 mg three times a day, a 14-year-old boy was admitted to our hospital because of mild fever, severe headache, slowness, drowsiness and vomiting. A cerebrospinal fluid examination was performed and showed an increased protein concentration (95 mg/dL), normal glucose level (48 mg/dL; blood glucose level, 76 mg/dL) and lymphocytic pleocytosis (1,400 lymphocytes/MUL), and VZV DNA was detected by means of polymerase chain reaction (1,250 copies/mL). The results of immunological screening for HIV, lymphocyte subpopulation counts, serum immunoglobulin and complement (C3 and C4) levels, vaccine responsiveness and lymphocytes stimulation tests were unremarkable. Acyclovir was administered intravenously at a dose of 10 mg/kg three times a day and continued for 10 days. The therapy was highly effective and the patient's clinical condition rapidly improved: fever disappeared after two days, and all of the signs and symptoms of neurological involvement after four days. The skin lesions resolved in about one week, and no pain or dysesthesia was ever reported. Given the favourable evolution of the illness, the child was discharged without further therapy after the 10-day treatment. The findings of a magnetic resonance examination immediately after the discontinuation of the antiviral therapy were normal, and a control examination carried out about four weeks later did not find any sign or symptom of disease. CONCLUSION: VZV reactivation can also lead to various neurological complications in immunocompetent children. Prompt therapy with acyclovir and the integrity of the immune system are important in conditioning outcome, but other currently unknown factors probably also play a role. PMID- 24224977 TI - Evaluation of wound care options in patients with recessive dystrophic epidermolysis bullosa: a costly necessity. AB - Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder in which mutations in collagen VII, the main component of the anchoring fibril, lead to skin fragility and to the development of acute and chronic wounds. Wound care and dressing changes are an important part of the daily lives of individuals with RDEB. Ideal wound care should improve wound healing, minimize pain, and improve quality of life. The objective of the current study was to review wound care options that might be used in a patient with RDEB and calculate the cost of these various options based on publicly available pricing of wound care products. There is a wide range of costs for wound care options in patients with RDEB. For example, a 1-day supply of dressing for a neonate boy with RDEB ranges from $10.64 for the least expensive option to $127.54 for the most expensive option. Wound care in patients with severe, generalized RDEB has not only a significant economic effect, but also directly affects quality of life in this patient population. Although randomized controlled trials evaluating different wound care products in patients with RDEB are lacking, small studies and expert opinion support the use of specialized nonadherent dressings that minimize skin trauma and promote wound healing. Until there is a cure, prospective studies are needed to assess pain, quality of life, and wound healing associated with the use of specialized wound care products for this life-altering condition. PMID- 24224978 TI - Acute compartment syndrome: clinical course and laboratory findings in pregnant patients with McArdle's disease. PMID- 24224979 TI - Dual-barrel conductance micropipet as a new approach to the study of ionic crystal dissolution kinetics. AB - A new approach to the study of ionic crystal dissolution kinetics is described, based on the use of a dual-barrel theta conductance micropipet. The solution in the pipet is undersaturated with respect to the crystal of interest, and when the meniscus at the end of the micropipet makes contact with a selected region of the crystal surface, dissolution occurs causing the solution composition to change. This is observed, with better than 1 ms time resolution, as a change in the ion conductance current, measured across a potential bias between an electrode in each barrel of the pipet. Key attributes of this new technique are: (i) dissolution can be targeted at a single crystal surface; (ii) multiple measurements can be made quickly and easily by moving the pipet to a new location on the surface; (iii) materials with a wide range of kinetics and solubilities are open to study because the duration of dissolution is controlled by the meniscus contact time; (iv) fast kinetics are readily amenable to study because of the intrinsically high mass transport rates within tapered micropipets; (v) the experimental geometry is well-defined, permitting finite element method modeling to allow quantitative analysis of experimental data. Herein, we study the dissolution of NaCl as an example system, with dissolution induced for just a few milliseconds, and estimate a first-order heterogeneous rate constant of 7.5 (+/-2.5) * 10(-5) cm s(-1) (equivalent surface dissolution flux ca. 0.5 MUmol cm( 2) s(-1) into a completely undersaturated solution). Ionic crystals form a huge class of materials whose dissolution properties are of considerable interest, and we thus anticipate that this new localized microscale surface approach will have considerable applicability in the future. PMID- 24224980 TI - Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L arginine-induced acute pancreatitis rat model. AB - BACKGROUND AND AIM: This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. METHODS: The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. RESULTS: Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1beta (P < 0.001) and tumor necrosis factor-alpha (P < 0.001); (iv) the significant inhibition of nuclear factor-kappaB (NF-kappaB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. CONCLUSIONS: Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-kappaB activation associated with acute pancreatitis. PMID- 24224981 TI - Successful treatment of myelodysplastic syndrome and chronic hepatitis C using combined peginterferon-alpha-2b and ribavirin therapy. AB - We report a patient with myelodysplastic syndrome (MDS) and hepatitis C virus (HCV) infection who was successfully treated with a combination of peginterferon and ribavirin therapy. A 65-year-old man was referred to our hospital for treatment of chronic hepatitis C and close examination of pancytopenia. MDS of "refractory cytopenia with multilineage dysplasia" was diagnosed on the basis of bone marrow findings. Although the patient was not a good candidate for interferon (IFN) therapy because of his pancytopenia, we decided to proceed with IFN therapy for the following reasons: his elevated transaminases could not be controlled; he had a high possibility of recovery from chronic hepatitis C in consideration of his HCV genotype 2a and relatively low RNA titer; and his pancytopenia was expected to worsen in the future. After combination peginterferon/ribavirin therapy, the patient achieved sustained viral response, and the bone marrow findings showed neutrophils with normal granulation and megakaryocytes with normal morphological features. Additionally, the normal 46, XY karyotype converted from 45, X0 which was found before IFN therapy. This suggested that the patient's MDS was completely resolved. PMID- 24224982 TI - Active lifestyles related to excellent self-rated health and quality of life: cross sectional findings from 194,545 participants in The 45 and Up Study. AB - BACKGROUND: Physical activity and sitting time independently contribute to chronic disease risk, though little work has focused on aspirational health outcomes. The purpose of this study was to examine associations between physical activity, sitting time, and excellent overall health (ExH) and quality of life (ExQoL) in Australian adults. METHODS: The 45 and Up Study is a large Australian prospective cohort study (n = 267,153). Present analyses are from 194,545 participants (48% male; mean age = 61.6 +/- 10.7 yrs) with complete baseline questionnaire data on exposures, outcomes, and potential confounders (age, income, education, smoking, marital status, weight status, sex, residential remoteness and economic advantage, functional limitation and chronic disease). The Active Australia survey was used to assess walking, moderate, and vigorous physical activity. Sitting time was determined by asking participants to indicate number of hours per day usually spent sitting. Participants reported overall health and quality of life, using a five-point scale (excellent-poor). Binary logistic regression models were used to analyze associations, controlling for potential confounders. RESULTS: Approximately 16.5% of participants reported ExH, and 25.7% reported ExQoL. In fully adjusted models, physical activity was positively associated with ExH (AOR = adjusted odds ratio for most versus least active = 2.22, 95% CI = 2.20, 2.47; P(trend) < 0.001) and ExQoL (AOR for most versus least active = 2.30, 95% CI = 2.12, 2.49; P(trend) < 0.001). In fully adjusted models, sitting time was inversely associated with ExH (AOR for least versus most sitting group = 1.13, 95% CI = 1.09, 1.18; P(trend) < 0.001) and ExQoL (AOR for least versus most sitting group = 1.13, 95% CI = 1.10, 1.17; P(trend) < 0.001). In fully adjusted models, interactions between physical activity and sitting time were not significant for ExH (P = 0.118) or ExQoL (P = 0.296). CONCLUSIONS: Physical activity and sitting time are independently associated with excellent health and quality of life in this large diverse sample of Australian middle-aged and older adults. These findings bolster evidence informing health promotion efforts to increase PA and decrease sitting time toward the achievement of better population health and the pursuit of successful aging. PMID- 24224984 TI - The development of methods to semiobjectively estimate auditory sensitivity for ototoxicity monitoring. PMID- 24224983 TI - Towards an HIV cure: science and debate from the International AIDS Society 2013 symposium. AB - The International AIDS Society convened the multi-stakeholder "Towards an HIV Cure" symposium in Kuala Lumpur, Malaysia in 2013 to address the significant research challenges posed by the search for a cure for HIV infection. Current antiretroviral regimens select for a small reservoir of cells that harbour latent HIV provirus, produce few or no HIV virions, and resist detection or clearance by host immunity. The symposium examined basic molecular science and animal model data, and emerging and ongoing clinical trial results to prioritise strategies and determine the viral and immune responses that could lead to HIV remission without ART. Here we review the presentations that scrutinized the molecular mechanisms controlling virus expression from proviral DNA, and the intrinsic cellular restriction and immune mechanisms preventing viral production. Insights from the basic science have translated into new therapeutic strategies seeking HIV remission without ongoing therapy, and much interest was focused on these ongoing trials. We also summarise the emerging ethical issues and patient expectations as concepts move into the clinic. PMID- 24224986 TI - Relationship between postural stability and spatial hearing. AB - BACKGROUND: Maintaining balance is known to be a multisensory process that uses information from different sensory organs. Although it has been known for a long time that spatial hearing cues provide humans with moderately accurate abilities to localize sound sources, how the auditory system interacts with balance mediated by the vestibular system remains largely a mystery. PURPOSE: The primary goal of the current study was to determine whether auditory spatial cues obtained from a fixed sound source can help human participants balance themselves as compared to conditions in which participants use vision. RESEARCH DESIGN: The experiment uses modified versions of conventional clinical tests: the Tandem Romberg test and the Fukuda Stepping test. In the Tandem Romberg test, participants stand with their feet in a heel-to-toe position, and try to maintain balance for 40 sec. In the Fukuda Stepping test, a participant is asked to close his or her eyes and to march in place for 100 steps. The sway and angular deviation of each participant was measured with and without vision and spatial auditory cues. An auditory spatial reference was provided by presenting a broadband noise source from a loudspeaker directly in front of the participant located 1-2 m away. STUDY SAMPLE: A total of 19 participants (11 women and 8 men; mean age = 27 yr; age range = 18~52 yr), voluntarily participated in the experiment. All participants had normal vision, hearing, and vestibular function. INTERVENTION: The primary intervention was the use of a broadband noise source to provide an auditory spatial referent for balance measurements in the Tandem Romberg test and Fukuda Stepping test. Conditions were also tested in which the participants had their eyes opened or closed. DATA COLLECTION AND ANALYSIS: A head tracker recorded the position of the participant's head for the Tandem Romberg test. The angular deviation of the feet after 100 steps was measured in the Fukuda Stepping test. An average distance or angle moved by the head or feet was calculated relative to the head or feet resting position for each test. The average head sway or angular deviation was measured in an eyes-open condition (no sound), eyes-closed condition (no sound), and an eyes-closed condition with sound. Repeated-measures analysis of variance was used for both tests. RESULTS: The results showed a significant benefit in postural stability in both experiments when spatial auditory cues were present (p < .01). For the Tandem Romberg test, the benefit from spatial auditory cues alone is a 9% reduction in mean sway, as compared to 44% from visual cues alone. For the Fukuda Stepping test, the benefit from spatial auditory cues alone is a 76% reduction in mean body sway, as compared to 98% from visual cues alone. CONCLUSIONS: The current study demonstrated a connection between spatial hearing and balance. The experiments showed that a single fixed sound source can provide sufficient spatial cues for the central nervous system to better control postural stability. The compensation effect that the vestibular system receives from the auditory cues, however, is weaker than that received from visual cues. PMID- 24224985 TI - ABR obtained from time-efficient train stimuli for cisplatin ototoxicity monitoring. AB - BACKGROUND: Nonbehavioral methods for identifying cisplatin ototoxicity are important for testing patients with cancer who become too tired or sick to provide a reliable response. The auditory brainstem response (ABR) is a nonbehavioral test that is sensitive to ototoxicity but can be time consuming to implement over a range of frequencies and/or levels. To address this issue, trains of stimuli were developed that offer reliable ABR testing over a range of tone-burst frequencies and levels at a time savings of 77% relative to tone-burst stimuli presented individually. The clinical accuracy of this new method has yet to be determined on a clinical population. PURPOSE: This project was designed to determine the test performance of a time-effective ABR methodology aimed at identifying hearing shifts from cisplatin among veterans. A secondary goal was to determine whether improved test performance could be achieved by including our previously developed ototoxicity risk assessment model in the ABR prediction algorithm. RESEARCH DESIGN: A set of discriminant functions were derived using logistic regression to model the risk for cisplatin-induced hearing change. Independent variables were one of several ABR metrics alone and combined with an ototoxicity risk assessment model that includes pre-exposure hearing and cisplatin dose. Receiver operating characteristic curve analysis was used to evaluate the test performance of these discriminant functions. STUDY SAMPLE: Twenty-two male veterans treated with cisplatin for various cancers provided data from a total of 71 monitoring appointments. DATA COLLECTION AND ANALYSIS: Data were collected prospectively from one ear of each participant as designated below. Hearing shift was determined for frequencies within an octave of each patient's high-frequency hearing limit, tested in 1/6th-octave steps. ABRs were monitored using a set of two intensity trains from the highest two multiple frequency tone-burst center frequencies (up to 11.3 kHz) that yielded a robust response at baseline. Each intensity train was presented at 65-105 dB peSPL in 10 dB steps. Scorable ABRs were generally limited to the highest two intensities; therefore, analyses concern those levels. RESULTS: The ABR measurement failure was high, up to 52% for some frequencies and levels. Furthermore, the ABR was not frequently obtained at levels below 85 dB peSPL, consistent with previous studies that suggest a stimulus level of greater than 80 dB peSPL is required to obtain a reliable response to trained stimuli. Using multivariate metrics that included the dose-ototoxicity model, the most accurate scoring function was change in amplitude at lowest half-octave frequency obtained at 105 dB (change in wave V amplitude at frequency 2/105). However, absence of wave V at a monitor patient visit of the ABR response at levels 105 or 95 dB peSPL was deemed the preferred scoring function, because it had lower measurement failure and was within one standard error of the most accurate function. CONCLUSIONS: Because of the large number of responses that could not be measured at baseline, this technique as implemented holds limited value as an ototoxicity-monitoring method. PMID- 24224987 TI - Tone, rhythm, and timbre perception in school-age children using cochlear implants and hearing aids. AB - BACKGROUND: Children with hearing impairments, especially those using hearing devices such as the cochlear implant (CI) or hearing aid (HA), are sometimes not encouraged to attend music classes, as they or their parents and teachers may be unsure whether the child can perform basic musical tasks. PURPOSE: The objective of the current study was to provide a baseline for the performance of children using CIs and HAs on standardized tests of rhythm and pitch perception as well as an instrument timbre identification task. An additional aim was to determine the effect of structured music training on these measures during the course of a school year. RESEARCH DESIGN: The Intermediate Measures of Music Audiation (IMMA) Tonal and Rhythmic subtests were administered four times, with 6 wk between tests. All children in the study were also enrolled in "Music Club" teaching sessions. Measures were compared between groups and across the four testing sessions. STUDY SAMPLE: Twenty children from a single school in Melbourne, Australia, were recruited. Eleven (four girls) had impaired hearing, including six with a unilateral CI or CI and HA together (two girls) and five with bilateral HAs (two girls). Nine were normally hearing, selected to match the age and gender of the hearing-impaired children. Ages ranged from 9-13 yr. INTERVENTION: All children participated in a weekly Music Club--a 45 min session of musical activities based around vocal play and the integration of aural, visual, and kinesthetic modes of learning. DATA COLLECTION AND ANALYSIS: Audiological data were collected from clinical files. IMMA scores were converted to percentile ranks using published norms. Between-group differences were tested using repeated-measures analysis of variance, and between-session differences were tested using a linear mixed model. Linear regression was used to model the effect of hearing loss on the test scores. RESULTS: In the first session, normally hearing children had a mean percentile rank of ~50 in both the Tonal and Rhythmic subtests of the IMMA. Children using CIs showed trends toward lower scores in the Tonal, but not the Rhythmic, subtests. No significant improvements were found between sessions. In the timbre test, children generally made fewer errors within the set of percussive compared to nonpercussive instruments. The hearing loss level partially predicted performance in the Tonal, but not the Rhythmic, task, and predictions were more significant for nonpercussive compared to percussive instruments. CONCLUSIONS: The findings highlight the importance of temporal cues in the perception of music, and indicate that temporal cues may be used by children with CIs and HAs in the perception of not only rhythm, but also of some aspects of timbre. We were not able to link participation in the Music Club with increased scores on the Tonal, Rhythmic, and Timbre tests. However, anecdotal evidence from the children and their teachers suggested a wide range of benefits from participation in the Music Club that extended from increased engagement and interest in music classes into the children's social situations. PMID- 24224988 TI - Cortical auditory-evoked potentials (CAEPs) in adults in response to filtered speech stimuli. AB - BACKGROUND: Previous studies have demonstrated that cortical auditory-evoked potentials (CAEPs) can be reliably elicited in response to speech stimuli in listeners wearing hearing aids. It is unclear, however, how close to the aided behavioral threshold (i.e., at what behavioral sensation level) a sound must be before a cortical response can reliably be detected. PURPOSE: The purpose of this study was to systematically examine the relationship between CAEP detection and the audibility of speech sounds (as measured behaviorally), when the listener is wearing a hearing aid fitted to prescriptive targets. A secondary aim was to investigate whether CAEP detection is affected by varying the frequency emphasis of stimuli, so as to simulate variations to the prescribed gain-frequency response of a hearing aid. The results have direct implications for the evaluation of hearing aid fittings in nonresponsive adult clients, and indirect implications for the evaluation of hearing aid fittings in infants. RESEARCH DESIGN: Participants wore hearing aids while listening to speech sounds presented in a sound field. Aided thresholds were measured, and cortical responses evoked, under a range of stimulus conditions. The presence or absence of CAEPs was determined by an automated statistic. STUDY SAMPLE: Participants were adults (6 females and 4 males). Participants had sensorineural hearing loss ranging from mild to severe-profound in degree. DATA COLLECTION AND ANALYSIS: Participants' own hearing aids were replaced with a test hearing aid, with linear processing, during assessments. Pure-tone thresholds and hearing aid gain measurements were obtained, and a theoretical prediction of speech stimulus audibility for each participant (similar to those used for audibility predictions in infant hearing aid fittings) was calculated. Three speech stimuli, (/m/, /t/, and /g/) were presented aided (monaurally, nontest ear occluded), free field, under three conditions (+4 dB/octave, -4 dB/octave, and without filtering), at levels of 40, 50, and 60 dB SPL (measured for the unfiltered condition). Behavioral thresholds were obtained, and CAEP recordings were made using these stimuli. The interaction of hearing loss, presentation levels, and filtering conditions resulted in a range of CAEP test behavioral sensation levels (SLs), from -25 to +40 dB. RESULTS: Statistically significant CAEPs (p < .05) were obtained for virtually every presentation where the behavioral sensation level was >10 dB, and for only 5% of occasions when the sensation level was negative. In these ("false positive") cases, the greatest (negative) sensation level at which a CAEP was judged to be present was -6 dB SL. CONCLUSIONS: CAEPs are a sensitive tool for directly evaluating the audibility of speech sounds, at least for adult listeners. CAEP evaluation was found to be more accurate than audibility predictions, based on threshold and hearing aid response measures. PMID- 24224989 TI - Acceptable noise levels in preschool children with normal hearing. AB - BACKGROUND: The acceptable noise level (ANL) measure is an indicator of hearing aid use. The majority of research in this area has focused primarily on adults. Research using school-aged listeners, specifically 8 and 12 yr old children, demonstrated that the average ANL values, standard deviations (SDs), and distribution of ANL values for these children were similar to those of adult listeners. Additionally, the ANL measure is reliable over time, even in school aged listeners. Although ANL values from adult and school-aged listeners have been investigated, no research to date has been conducted using preschool children. PURPOSE: The purpose of the present study was to determine if ANLs could be obtained in preschool children, aged 4 and 5 yr, with normal hearing. This study also aimed to investigate the reliability and distribution of ANL measurements from preschool children, as well as any effect that background noise might present in the listening environment. RESEARCH DESIGN: Seated in a sound treated test suite, listeners were tasked with adjusting speech stimuli to their most comfortable listening level; then, with speech present, listeners were tasked with adjusting the background noise to their most acceptable background noise level. Three trials of each measure were averaged and were used to calculate each listener's ANL. STUDY SAMPLE: ANLs were attempted on 23 children, ages 4 yr (N = 14) to 5 yr (N = 9), with normal hearing. RESULTS: Less than half of the 4 yr old listeners performed the ANL task, whereas all of the 5 yr old listeners completed the task successfully. Good test-retest reliability was found for those preschool children who were able to complete the task. Mean ANLs, SDs, ranges, and distributions demonstrated that these values agree with ANL data collected from older school-aged listeners. CONCLUSIONS: Although ANL values were reliably measured in all of the 5 yr old listeners, this was not the case for 4 yr old listeners. ANL values were not reliably obtained from 4 yr old listeners; however, the ANL procedure is appropriate for use for 5 yr old listeners. Furthermore, ANL means, SDs, ranges, and distributions were in agreement with those from older school-aged children and adults, and ANLs in preschool listeners were unaffected by the type of background noise stimuli. PMID- 24224990 TI - Hearing impaired children's preference for, and performance with, four combinations of directional microphone and digital noise reduction technology. AB - BACKGROUND: Before advanced noise-management features can be recommended for use in children with hearing loss, evidence regarding their ability to use these features to optimize speech perception is necessary. PURPOSE: The purpose of this study was to examine the relation between children's preference for, and performance with, four combinations of noise-management features in noisy listening environments. RESEARCH DESIGN: Children with hearing loss were asked to repeat short sentences presented in steady-state noise or in multitalker babble while wearing ear-level hearing aids. The aids were programmed with four memories having an orthogonal arrangement of two noise-management features. The children were also asked to indicate the hearing aid memory that they preferred in each of the listening conditions both initially and after a short period of use. STUDY SAMPLE: Fifteen children between the ages of 8 and 12 yr with moderate hearing losses, bilaterally. RESULTS: The children's preference for noise management aligned well with their performance for at least three of the four listening conditions. The configuration of noise-management features had little effect on speech perception with the exception of reduced performance for speech originating from behind the child while in a directional hearing aid setting. Additionally, the children's preference appeared to be governed by listening comfort, even under conditions for which a benefit was not expected such as the use of digital noise reduction in the multitalker babble conditions. CONCLUSIONS: The results serve as evidence in support of the use of noise-management features in grade-school children as young as 8 yr of age. PMID- 24224991 TI - Effects of a transient noise reduction algorithm on speech understanding, subjective preference, and preferred gain. AB - BACKGROUND: Today's compression hearing aids with noise reduction systems may not manage transient noises effectively because of the short duration of these sounds compared to the onset times of the compressors and/or noise reduction algorithms. PURPOSE: The current study was designed to evaluate the effect of a transient noise reduction (TNR) algorithm on listening comfort, speech intelligibility in quiet, and preferred wearer gain in the presence of transients. RESEARCH DESIGN: A single-blinded, repeated-measures design was used. STUDY SAMPLE: Thirteen experienced hearing aid users with bilaterally symmetrical (<=7.5 dB) sensorineural hearing loss participated in the study. RESULTS: Speech identification in quiet (no transient noise) was identical between the TNR On and the TNR Off conditions. The participants showed subjective preference for the TNR algorithm when "comfortable listening" was used as the criterion. Participants preferred less gain than the default prescription in the presence of transient noise sounds. However, the preferred gain was 2.9 dB higher when the TNR was activated than when it was deactivated. This translated to 12.1% improvement in phoneme identification over the TNR Off condition for soft speech. CONCLUSIONS: This study demonstrated that the use of the TNR algorithm would not negatively affect speech identification. The results also suggested that this algorithm may improve listening comfort in the presence of transient noise sounds and ensure consistent use of prescribed gain. Such an algorithm may ensure more consistent audibility across listening environments. PMID- 24224992 TI - Optimizing otoscopy competency in audiology students through supplementary otoscopy training. AB - BACKGROUND: Scope of practice in audiology encompasses proficiency in visual inspection of ear canal and tympanic membrane (TM) as well as otoscopy interpretation skills to determine normal versus abnormal conditions of outer and middle ear. Audiology students can develop skills in otoscopy through education and supervised training. Studies have shown that additional otoscopy training increased skills in medical students and general practitioners. However, educational and supervised practices targeting otoscopy competency during audiology graduate coursework are lacking. Also, no studies have attempted to determine otoscopy skills among audiology students. PURPOSE: To determine the effectiveness of the otoscopy training model on clinical competency and confidence level of audiology students in performing and interpreting otoscopy. RESEARCH DESIGN: A combination of experimental treatment design with random assignment of treatment and control groups and delayed treatment for control group. STUDY SAMPLE: Thirty-two first- and second-year audiology graduate students who were enrolled in a pediatric audiology class participated in this study. Students were randomly assigned to the control (n = 16, 14 females) or experimental (n = 16, 14 females) group. INTERVENTION: Participants in the experimental group received supplementary otoscopy training including didactic otoscopy lectures as well as clinical training using manikin ears. The control group received the same pretest and posttest and then completed a third assessment (posttest 2) after receiving the same training. DATA COLLECTION AND ANALYSIS: An evaluation of knowledge and skills regarding otoscopy between groups and time was conducted at three times: (a) pretraining, (b) upon completion of training for the experimental group, (c) upon completion of training by the control group. The evaluation consisted of a written exam, a clinical exam, and a self-perception rating of confidence. Both written exam scores and clinical exam scores (otoscopy manikin) were analyzed via two-way analyses of variance (ANOVAs), whereas chi-square (chi2) statistic was conducted to evaluate the effects of training on the confidence level of students of both groups. RESULTS: Experimental and control groups demonstrated significant increased overall competency in otoscopy following the otoscopy training model with didactic and laboratory components. Posttest confidence ratings showed increases in all groups, and there were no significant differences between groups. CONCLUSIONS: The need for supplementary otoscopy training was warranted by low knowledge and clinical competency in otoscopy skills of audiology students as measured by pretest mean scores. After completing the training, both experimental and control groups showed significant improvement in knowledge and competency. Results also suggest that perceived confidence ratings may be misleading in determining students' clinical otoscopy skills. PMID- 24224993 TI - Screening Test for Auditory Processing (STAP): a preliminary report. AB - BACKGROUND: The presence of auditory processing disorder in school-age children has been documented (Katz and Wilde, 1985; Chermak and Musiek, 1997; Jerger and Musiek, 2000; Muthuselvi and Yathiraj, 2009). In order to identify these children early, there is a need for a screening test that is not very time-consuming. PURPOSE: The present study aimed to evaluate the independence of four subsections of the Screening Test for Auditory Processing (STAP) developed by Yathiraj and Maggu (2012). The test was designed to address auditory separation/closure, binaural integration, temporal resolution, and auditory memory in school-age children. The study also aimed to examine the number of children who are at risk for different auditory processes. RESEARCH DESIGN: Factor analysis research design was used in the current study. STUDY SAMPLE: Four hundred school-age children consisting of 218 males and 182 females were randomly selected from 2400 children attending three schools. The children, aged 8 to 13 yr, were in grade three to eight class placements. DATA COLLECTION AND ANALYSES: The children were evaluated on the four subsections of the STAP (speech perception in noise, dichotic consonant-vowel [CV], gap detection, and auditory memory) in a quiet room within their school. The responses were analyzed using principal component analysis (PCA) and confirmatory factor analysis (CFA). In addition, the data were also analyzed to determine the number of children who were at risk for an auditory processing disorder (APD). RESULTS: Based on the PCA, three components with Eigen values greater than 1 were extracted. The orthogonal rotation of the variables using the Varimax technique revealed that component 1 consisted of binaural integration, component 2 consisted of temporal resolution, and component 3 was shared by auditory separation/closure and auditory memory. These findings were confirmed using CFA, where the predicted model displayed a good fit with or without the inclusion of the auditory memory subsection. It was determined that 16% of the children were at risk for APD on one or more of the subsections of STAP. Among these 16%, the auditory memory subsection was the most affected (73.4%), followed by binaural integration (65.6%), auditory separation/closure (59.4%), and temporal resolution (53.1%). CONCLUSION: The current study revealed that the four subsections of STAP merged to form three distinct components. Dichotic CV and gap detection formed two independent components while speech perception in noise and auditory memory merged to form a single component. This indicates a possible relationship between auditory memory and speech perception in noise as suggested by Katz (1992). Thus, STAP is able to detect three different components related to auditory processing. The study also indicates that the number of children at risk for each of the different auditory processes vary. Ongoing evaluation will shed light on the usefulness of the subsections of STAP in identifying auditory processing problems. In addition to conducting the APD screening test, it is also recommended that a hearing screening be done to rule out peripheral hearing problems when hearing screening programs are not conducted in schools. PMID- 24224994 TI - Identification of vowel length, word stress, and compound words and phrases by postlingually deafened cochlear implant listeners. AB - BACKGROUND: The accurate perception of prosody assists a listener in deriving meaning from natural speech. Few studies have addressed the ability of cochlear implant (CI) listeners to perceive the brief duration prosodic cues involved in contrastive vowel length, word stress, and compound word and phrase identification. PURPOSE: To compare performance in the perception of brief duration prosodic contrasts by CI participants and a control group of normal hearing participants. This study investigated the ability to perceive these cues in quiet and noise conditions, and to identify auditory perceptual factors that might predict prosodic perception in the CI group. Prosodic perception was studied both in noise and quiet because noise is a pervasive feature of everyday environments. RESEARCH DESIGN: A quasi-experimental correlation design was employed. STUDY SAMPLE: Twenty-one CI recipients participated along with a control group of 10 normal hearing participants. All CI participants were unilaterally implanted adults who had considerable experience with oral language prior to implantation. DATA COLLECTION AND ANALYSIS: Speech identification testing measured the participants' ability to identify word stress, vowel length, and compound words or phrases all of which were presented with minimal-pair response choices. Tests were performed in quiet and in speech-spectrum shaped noise at a 10 dB signal-to-noise ratio. Also, discrimination thresholds for four acoustic properties of a synthetic vowel were measured as possible predictors of prosodic perception. Testing was carried out during one session, and participants used their clinically assigned speech processors. RESULTS: The CI group could not identify brief prosodic cues as well as the control group, and their performance decreased significantly in the noise condition. Regression analysis showed that the discrimination of intensity predicted performance on the prosodic tasks. The performance decline measured with the older participants meant that age also emerged as a predictor. CONCLUSIONS: This study provides a portrayal of CI recipients' ability to perceive brief prosodic cues. This is of interest in the preparation of rehabilitation materials used in training and in developing realistic expectations for potential CI candidates. PMID- 24224996 TI - Cortical contusion injury disrupts olfactory bulb neurogenesis in adult mice. AB - BACKGROUND: Experimental brain trauma activates quiescent neural stem cells (NSCs) to increase neuronal progenitor cell proliferation in the adult rodent brain. Previous studies have shown focal brain contusion in the form of a unilateral controlled cortical impact (CCI) stimulates NSCs to bilaterally increase neurogenesis in the adult hippocampus. RESULTS: In this study we clarified the bi-lateral effects of a unilateral CCI on proliferation in the subventricular zone (SVZ) NSC niche and on neurogenesis in the olfactory bulb of adult mice. By varying the depth of impact from 1 mm to 2 mm depth, we show CCI to the left somatosensory cortex resulted in graded changes in mouse behavior and cellular pathology in the forebrain. As expected, contusion to the sensorimotor cortex resulted in motor coordination deficits in adult mice. During the first 3 days after injury, CCI increased proliferation in the impacted cortex, deeper striatum and SVZ of the forebrain ipsilateral to the CCI. In each of these regions proliferation was increased with increasing injury severity. At 30 days post-procedure, CCI resulted in a significant reduction in neurogenesis in the olfactory bulb ipsilateral to the CCI. Olfactory avoidance testing indicated disruptions in olfactory bulb neurogenesis were associated with impaired olfactory discrimination in mice post-injury. CONCLUSION: The data demonstrate a focal cortical contusion injury to the left somatosensory cortex disrupts SVZ olfactory bulb neurogenesis and impairs olfactory discrimination and motor coordination in adult mice. PMID- 24224997 TI - Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. AB - BACKGROUND: The TARGIT-A trial compared risk-adapted radiotherapy using single dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. METHODS: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2.5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. FINDINGS: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15.2% [239 of 1571] of patients who received TARGIT (21.6% prepathology, 3.6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3.3% (95% CI 2.1 5.1) for TARGIT versus 1.3% (0.7-2.5) for EBRT (p=0.042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2.1% (1.1-4.2) versus 1.1% (0.5-2.5; p=0.31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2.5% (TARGIT 5.4% [3.0-9.7] vs EBRT 1.7% [0.6-4.9]; p=0.069). Overall, breast cancer mortality was much the same between groups (2.6% [1.5-4.3] for TARGIT vs 1.9% [1.1-3.2] for EBRT; p=0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4% [0.8-2.5] vs 3.5% [2.3-5.2]; p=0.0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3.9% (2.7-5.8) for TARGIT versus 5.3% (3.9-7.3) for EBRT (p=0.099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0.029). INTERPRETATION: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research. PMID- 24224998 TI - Intraoperative radiotherapy for breast cancer. PMID- 24224999 TI - 18F-fluoride positron emission tomography for identification of ruptured and high risk coronary atherosclerotic plaques: a prospective clinical trial. AB - BACKGROUND: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F FDG). METHODS: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. FINDINGS: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1.66 [IQR 1.40-2.25] vs highest non-culprit 1.24 [1.06-1.38], p<0.0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1.71 [1.40-2.13] vs 1.58 [1.28-2.01], p=0.34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1.90 [IQR 1.61-2.17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1.12 [1.09-1.19] vs 1.01 [0.94-1.06]; p=0.0004), microcalcification (73% vs 21%, p=0.002), and necrotic core (25% [21 29] vs 18% [14-22], p=0.001). INTERPRETATION: (18)F-NaF PET-CT is the first non invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. FUNDING: Chief Scientist Office Scotland and British Heart Foundation. PMID- 24225000 TI - A new frontier in atherosclerotic coronary imaging. PMID- 24225001 TI - Colorectal cancer. AB - More than 1.2 million patients are diagnosed with colorectal cancer every year, and more than 600,000 die from the disease. Incidence strongly varies globally and is closely linked to elements of a so-called western lifestyle. Incidence is higher in men than women and strongly increases with age; median age at diagnosis is about 70 years in developed countries. Despite strong hereditary components, most cases of colorectal cancer are sporadic and develop slowly over several years through the adenoma-carcinoma sequence. The cornerstones of therapy are surgery, neoadjuvant radiotherapy (for patients with rectal cancer), and adjuvant chemotherapy (for patients with stage III/IV and high-risk stage II colon cancer). 5-year relative survival ranges from greater than 90% in patients with stage I disease to slightly greater than 10% in patients with stage IV disease. Screening has been shown to reduce colorectal cancer incidence and mortality, but organised screening programmes are still to be implemented in most countries. PMID- 24225002 TI - Migrant background and ethnic minority status as predictors for duration of untreated psychosis. AB - AIM: The aim of the study was to explore if patients with migration and/or ethnic minority background have longer duration of untreated psychosis (DUP) than patients from the reference population, and in case to what extent this was best explained by ethnic minority status or migration background, including age at migration. METHODS: Four hundred sixty-two first-episode patients were included. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders was used for diagnostic purposes. Patients were interviewed about migration history and ethnicity using structured questionnaires. RESULTS: Being part of an ethnic minority group had a trend-level significance, and migration after the age of 6 had a statistically significant association with prolonged DUP. CONCLUSIONS: Age at migration has a moderate, but statistically significant effect on DUP. The findings indicate migrating after school start is associated with a longer DUP in immigrant populations. PMID- 24225003 TI - Sympathetic ophthalmia with sensorineural deafness - report of a case. AB - BACKGROUND: The aim of this study is to report a case of sympathetic ophthalmia with sensorineural hearing loss following penetrating trauma. This is an interventional case report. A 23-year-old male presented with bilateral, sudden, profound visual and hearing loss, disorientation, and dizziness. He had a past history of penetrating trauma with an iron rod in the right eye for which he underwent scleral tear repair, vitreo-retinal surgery with intraocular foreign body removal and silicon oil injection. His best corrected visual acuity in the right eye was counting fingers close to the face and was perception of light in the left eye. Clinical evaluation with slit biomicroscopy, indirect ophthalmoscopy, ultrasonography, and pure tone audiometry was suggestive of sympathetic ophthalmia with sensorineural hearing loss. Treatment was started with intravenous methyl prednisolone, oral corticosteroids, and immunosuppressants. FINDINGS: Following treatment, signs of panuveitis showed resolution and improvement in visual, hearing, and neurological symptoms. CONCLUSIONS: Sympathetic ophthalmia associated with sensorineural deafness and neurological symptoms is a rare clinical syndrome. Prompt diagnosis and treatment with systemic corticosteroids and immunosuppressant medication may result in clinical improvement. PMID- 24225004 TI - Evaluation of ELISA coupled with Western blot as a surveillance tool for Trichinella infection in wild boar (Sus scrofa). AB - Trichinella surveillance in wildlife relies on muscle digestion of large samples which are logistically difficult to store and transport in remote and tropical regions as well as labour-intensive to process. Serological methods such as enzyme-linked immunosorbent assays (ELISAs) offer rapid, cost-effective alternatives for surveillance but should be paired with additional tests because of the high false-positive rates encountered in wildlife. We investigated the utility of ELISAs coupled with Western blot (WB) in providing evidence of Trichinella exposure or infection in wild boar. Serum samples were collected from 673 wild boar from a high- and low-risk region for Trichinella introduction within mainland Australia, which is considered Trichinella-free. Sera were examined using both an 'in-house' and a commercially available indirect-ELISA that used excretory-secretory (E/S) antigens. Cut-off values for positive results were determined using sera from the low-risk population. All wild boar from the high-risk region (352) and 139/321 (43.3%) of the wild boar from the low-risk region were tested by artificial digestion. Testing by Western blot using E/S antigens, and a Trichinella-specific real-time PCR was also carried out on all ELISA-positive samples. The two ELISAs correctly classified all positive controls as well as one naturally infected wild boar from Gabba Island in the Torres Strait. In both the high- and low-risk populations, the ELISA results showed substantial agreement (k-value=0.66) that increased to very good (k-value=0.82) when WB-positive only samples were compared. The results of testing sera collected from the Australian mainland showed the Trichinella seroprevalence was 3.5% (95% C.I. 0.0-8.0) and 2.3% (95% C.I. 0.0-5.6) using the in-house and commercial ELISA coupled with WB respectively. These estimates were significantly higher (P<0.05) than the artificial digestion estimate of 0.0% (95% C.I. 0.0 1.1). Real-time PCR testing of muscle from seropositive animals did not detect Trichinella DNA in any mainland animals, but did reveal the presence of a second larvae-positive wild boar on Gabba Island, supporting its utility as an alternative, highly sensitive method in muscle examination. The serology results suggest Australian wildlife may have been exposed to Trichinella parasites. However, because of the possibility of non-specific reactions with other parasitic infections, more work using well-defined cohorts of positive and negative samples is required. Even if the specificity of the ELISAs is proven to be low, their ability to correctly classify the small number of true positive sera in this study indicates utility in screening wild boar populations for reactive sera which can be followed up with additional testing. PMID- 24225005 TI - Neighborhood differences in social capital in Ghent (Belgium): a multilevel approach. AB - BACKGROUND: Little research has focused on the spatial distribution of social capital, despite social capital's rising popularity in health research and policy. This study examines the neighborhood differences in social capital and the determinants that explain these differences. METHODS: Five components of neighborhood social capital are identified by means of factor and reliability analyses using data collected in the cross-sectional SWING study from 762 inhabitants in 42 neighbourhoods in the city of Ghent (Belgium). Neighborhood differences in social capital are explored using hierarchical linear models with cross-level interactions. RESULTS: Significant neighborhood differences are found for social cohesion, informal social control and social support, but not for social leverage and generalized trust. Our findings suggest that neighborhood social capital depends on both characteristics of individuals living in the neighborhood (attachment to neighborhood) and characteristics of the neighborhood itself (deprivation and residential turnover). Our analysis further shows that neighborhood deprivation reinforces the negative effect of declining neighborhood attachment on social cohesion and informal social control. CONCLUSIONS: This study foregrounds the importance of contextual effects in encouraging neighborhood social capital. Given the importance of neighborhood-level characteristics, it can be anticipated social capital promoting initiatives are likely to be more effective when tailored to specific areas. Second, our analyses show that not all forms of social capital are influenced by contextual factors to the same extent, implying that changes in neighborhood characteristics are conducive to, say, trust while leaving social support unaffected. Finally, our analysis has demonstrated that complex interrelationships between individual- and neighborhood-level variables exist, which are often overlooked in current work. PMID- 24225006 TI - Neurovascular protection by post-ischemic intravenous injections of the lipoxin A4 receptor agonist, BML-111, in a rat model of ischemic stroke. AB - Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA4 ) is an anti-inflammatory, pro-resolution lipid mediator with high affinity binding to ALX, the lipoxin A4 receptor. Since LXA4 is rapidly inactivated, potent analogs have been created, including the ALX agonist BML-111. We hypothesized that post-ischemic intravenous administration of BML-111 would provide protection to the neurovascular unit and reduce neuroinflammation in a rat stroke model. Animals were subjected to 90 min of middle cerebral artery occlusion (MCAO) and BML-111 was injected 100 min and 24 h after stroke onset and animals euthanized at 48 h. Post-ischemic treatment with BML-111 significantly reduced infarct size, decreased vasogenic edema, protected against blood-brain barrier disruption, and reduced hemorrhagic transformation. Matrix metalloproteinase-9 and matrix metalloproteinase-3 were significantly reduced following BML-111 treatment. Administration of BML-111 dramatically decreased microglial activation, as seen with CD68, and neutrophil infiltration and recruitment, as assessed by levels of myeloperoxidase and intracellular adhesion molecule-1. The tight junction protein zona occludens-1 was protected from degradation following treatment with BML-111. These results indicate that post-ischemic activation of ALX has pro-resolution effects that limit the inflammatory damage in the cerebral cortex and helps maintain blood-brain barrier integrity after ischemic stroke. PMID- 24225007 TI - [Malignant pleural mesothelioma: 2013 state of the art]. AB - Malignant pleural mesothelioma (MPM) is a bad-prognosis cancer raising difficult issues according to diagnosis. Reliable histological diagnosis indeed requires large-sized pathological samples obtained by thoracoscopy, and need diagnosis certification by the MESOPATH national expert pathological committee. MPM epidemiology shows a rising incidence among females, whereas an incidence plateau has been reached for males in France. The incidence peak is still predicted for 2030 decade in UK, Australia and North America, because of the asbestosis massive use in their industry until the end of 1980 decade. Pleural carcinogenesis is better understood with the recent discovery of BAP1 susceptibility gene although no oncogenic driver has been ever uncovered for targeted therapies, although several more or less targeted biological therapies are currently tested in early phase or more advanced-phase trials. Surgery is more and more questioned, since radical surgery is currently abandoned, whereas debulking or cyto-reduction surgery has been proposed within a multimodality approach also including adjuvant chemotherapy and radiotherapy but still need prospective trials. Pemetrexed and cisplatin-based chemotherapy remains the reference treatment, which has proved in mesothelioma some efficacy on overall survival in randomized trials, with a 13-15 months median-overall survival. Final results of the large phase 3 clinical trial "MAPS" sponsored by French collaborative Intergroup (IFCT) evaluating the effect of bevacizumab addition to pemetrexed-cisplatin doublet will be released in early 2015, since 445 patients have been included by November 2013. PMID- 24225008 TI - What is the best screening test for depression in chronic spinal pain patients? AB - BACKGROUND CONTEXT: High prevalence rates of depression have been found in patients with chronic spinal disorder (CSD). The biopsychosocial model has become widely adopted and, with it, the role of psychopathology in the development and/or exacerbation of CSD has become increasingly recognized. Standardized diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), have been used to diagnose major depressive disorder (MDD). Many measures of MDD (and depressive symptom inventories) have been developed during the past 50 years, but their comparative utility in CSD populations is still unclear. PURPOSE: To systemically compare the performance of depression screening questionnaires in detecting MDD among a large sample of patients with CSD. STUDY DESIGN/SETTING: Prospective cohort study comparing the screening ability of four popular depression measures for diagnosing MDD against the "gold standard" Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), using a receiver operating characteristic (ROC) analysis in a CSD population. PATIENT SAMPLE: A consecutive cohort of 546 patients with CSD admitted to an interdisciplinary functional restoration program. OUTCOME MEASURES: Sensitivity, specificity, ROC curves, area under the curve (AUC), and optimal cutoff points that are most closely related to the prevalence rates of MDD, with balanced sensitivity and specificity analysis. METHODS: Using the SCID-I diagnosis as a "gold standard," the ability of four screening measures in detecting MDD were compared. These included: the Beck Depression Inventory (BDI); Hamilton Rating Scale for Depression (HRSD); 9-Item Patient Health Questionnaire Depression Module (PHQ-9); and the Short Form-36 (SF-36). RESULTS: Of 542 CSD patients, 331 (61.1%) were diagnosed with MDD by the SCID-I. Results of the ROC analysis revealed that the BDI (AUC 0.768), HRSD (AUC 0.796), and PHQ-9 (AUC 0.768) have similar abilities to discriminate between depressed and nondepressed patients in this population. These depression measures outperformed the two mental health scales derived from the SF-36 (Mental Component Summary score/5-Item Mental Health Index; AUC 0.679-0.715). The optimal cut-off scores of 15 (for the BDI), 17 (for the HRSD), and 10 (for the PHQ-9) were also determined. Although the greatest overall accuracy (sensitivity of 81.3% and specificity of 65.4%) was obtained with the HRSD, it is the only clinician-administered instrument. Self report measures of depression (the BDI and PHQ-9) showed comparable abilities to detect depression, only slightly less than the HRSD. CONCLUSIONS: Compared to the HRSD, both BDI and PHQ-9 are relatively short and easy to self-administer. The cut-off scores established in this study may be used to reliably determine whether a person should be evaluated more thoroughly for an MDD diagnosis. Using an acknowledged "gold standard," the HRSD, BDI and PHQ-9 showed similar validity to recommend their use for future clinical and research purposes. The SF-36 is less appropriate for diagnosing MDD. PMID- 24225009 TI - Predicting C5 palsy via the use of preoperative anatomic measurements. AB - BACKGROUND CONTEXT: C5 nerve root palsy (C5P) is a relatively rare complication after anterior and posterior cervical decompression surgery that leads to a variety of debilitating symptoms. The precise etiology remains obscure, and a clear understanding of preoperative risk factors for C5P development does not exist. PURPOSE: To determine whether postoperative C5P can be predicted from preoperative anteroposterior diameter (APD), foraminal diameter (FD), and/or cord lamina angle (CLA). STUDY DESIGN: Retrospective review. PATIENT SAMPLE: Consecutive patients who underwent either anterior or posterior decompression surgery at C4-C5 for cervical spondylotic myelopathy. OUTCOME MEASURES: Development of C5P. METHODS: Blinded reviewers retrospectively assessed magnetic resonance images for each included patient's C4-C5 interspace, including the midline APD, the left and right FDs, and the left and right CLA. Multivariable logistic regression was used to model the probability of palsy on the basis of one or more predictors. A jackknife validation was performed to internally validate the model and assess its generalizability. RESULTS: A total of 98 patients fit the inclusion criteria; 12% had developed symptoms of C5 palsy postoperatively. Using the three variables in a predictor-model, we found that the odds ratio of having palsy for APD, FD, and CLA was 0.3, 0.02, and 1.4, respectively. For every 1-mm increase in APD and FD, the odds of developing palsy decrease 69% (p<.0001) and decrease 98% (p<.0003), respectively. In contrast, for every 1-degree increase in CLA, the odds of developing palsy increase by 43% (p<.0001). The receiver-operating characteristic curve for this three-variable model predicting development of palsy has an area under the curve (concordance index) of 0.97. After implementing a jackknife validation, the area under the curve was 95%. CONCLUSIONS: This study is the first to use the combination of APD, FD, and CLA to predict development of postoperative C5 palsy after decompression surgery for patients with spondylotic myelopathy. This prediction formula may allow for better patient selection and to prepare patients that have an increased probability of developing this complication. PMID- 24225010 TI - Spinal manipulative therapy and exercise for seniors with chronic neck pain. AB - BACKGROUND CONTEXT: Neck pain, common among the elderly population, has considerable implications on health and quality of life. Evidence supports the use of spinal manipulative therapy (SMT) and exercise to treat neck pain; however, no studies to date have evaluated the effectiveness of these therapies specifically in seniors. PURPOSE: To assess the relative effectiveness of SMT and supervised rehabilitative exercise, both in combination with and compared to home exercise (HE) alone for neck pain in individuals ages 65 years or older. STUDY DESIGN/SETTING: Randomized clinical trial. PATIENT SAMPLE: Individuals 65 years of age or older with a primary complaint of mechanical neck pain, rated >=3 (0 10) for 12 weeks or longer in duration. OUTCOME MEASURES: Patient self-report outcomes were collected at baseline and 4, 12, 26, and 52 weeks after randomization. The primary outcome was pain, measured by an 11-box numerical rating scale. Secondary outcomes included disability (Neck Disability Index), general health status (Medical Outcomes Study Short Form-36), satisfaction (7 point scale), improvement (9-point scale), and medication use (days per week). METHODS: This study was funded by the US Department of Health and Human Services, Health Resources and Services Administration. Linear mixed model analyses were used for comparisons at individual time points and for short- and long-term analyses. Blinded evaluations of objective outcomes were performed at baseline and 12 weeks. Adverse event data were collected at each treatment visit. RESULTS: A total of 241 participants were randomized, with 95% reporting primary outcome data at all time points. After 12 weeks of treatment, the SMT with home exercise group demonstrated a 10% greater decrease in pain compared with the HE-alone group, and 5% change over supervised plus home exercise. A decrease in pain favoring supervised plus HE over HE alone did not reach statistical significance. Compared with the HE group, both combination groups reported greater improvement at week 12 and more satisfaction at all time points. Multivariate longitudinal analysis incorporating primary and secondary patient-rated outcomes showed that the SMT with HE group was superior to the HE-alone group in both the short- and long-term. No serious adverse events were observed as a result of the study treatments. CONCLUSIONS: SMT with HE resulted in greater pain reduction after 12 weeks of treatment compared with both supervised plus HE and HE alone. Supervised exercise sessions added little benefit to the HE-alone program. PMID- 24225011 TI - Automatic exposure control at single- and dual-heartbeat CTCA on a 320-MDCT volume scanner: effect of heart rate, exposure phase window setting, and reconstruction algorithm. AB - PURPOSE: To investigate whether electrocardiogram (ECG)-gated single- and dual heartbeat computed tomography coronary angiography (CTCA) with automatic exposure control (AEC) yields images with uniform image noise at reduced radiation doses. MATERIALS AND METHODS: Using an anthropomorphic chest CT phantom we performed prospectively ECG-gated single- and dual-heartbeat CTCA on a second-generation 320-multidetector CT volume scanner. The exposure phase window was set at 75%, 70 80%, 40-80%, and 0-100% and the heart rate at 60 or 80 or corr80 bpm; images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR, adaptive iterative dose reduction 3D). We applied AEC and set the image noise level to 20 or 25 HU. For each technique we determined the image noise and the radiation dose to the phantom center. RESULTS: With half-scan reconstruction at 60 bpm, a 70-80% phase window- and a 20-HU standard deviation (SD) setting, the imagenoise level and -variation along the z axis manifested similar curves with FBP and IR. With half-scan reconstruction, the radiation dose to the phantom center with 70-80% phase window was 18.89 and 12.34 mGy for FBP and 4.61 and 3.10 mGy for IR at an SD setting SD of 20 and 25 HU, respectively. At 80 bpm with two segment reconstruction the dose was approximately twice that of 60 bpm at both SD settings. However, increasing radiation dose at corr80 bpm was suppressed to 1.39 times compared to 60 bpm. CONCLUSION: AEC at ECG-gated single- and dual-heartbeat CTCA controls the image noise at different radiation dose. PMID- 24225012 TI - Characterisation of a high resolution small field of view portable gamma camera. AB - A handheld, high-resolution small field of view (SFOV) pinhole gamma camera has been characterised using a new set of protocols adapted from standards previously developed for large field of view (LFOV) systems. Parameters investigated include intrinsic and extrinsic spatial resolution, spatial linearity, uniformity, sensitivity, count rate capability and energy resolution. Camera characteristics are compared to some clinical LFOV gamma cameras and also to other SFOV cameras in development. PMID- 24225013 TI - Moving upstream: a review of the evidence of the impact of outpatient palliative care. AB - BACKGROUND: There is good evidence for the efficacy of inpatient palliative care in improving clinical care, patient and provider satisfaction, quality of life, and health care utilization. However, the evidence for the efficacy of nonhospice outpatient palliative care is less well known and has not been comprehensively reviewed. OBJECTIVE: To review and assess the evidence of the impact of outpatient palliative care. METHODS: Our study was a review of published, peer reviewed outcomes research, including both observational studies and controlled trials of nonhospice outpatient palliative care services. We assessed patient, family caregiver, and clinician satisfaction; clinical outcomes including symptom management, quality of life, and mortality; and heath care utilization outcomes including readmission rates, hospice use, and cost. RESULTS: Four well-designed randomized interventions as well as a growing body of nonrandomized studies indicate that outpatient palliative care services can: 1) improve patient satisfaction, 2) improve symptom control and quality of life, 3) reduce health care utilization, and 4) lengthen survival in a population of lung cancer patients. CONCLUSIONS: The available evidence supports the ongoing expansion of innovative outpatient palliative care service models throughout the care continuum to all patients with serious illness. PMID- 24225015 TI - Accessible online neuroplasticity-targeted training for children with ADHD. AB - Childhood Attention Deficit Hyperactivity Disorder (ADHD) is a growing mental health concern worldwide. Effective, accessible and low-cost therapeutics for the disorder are urgently needed. Here we introduce a novel internet-based cognitive training intervention: Online Neuroplasticity-based Training for the Remediation of ADHD in Children (ONTRAC). The intervention is deployed in the home setting; it is customized to the cognitive capacities of each child and progressively improves performance in the specific neuro-cognitive domains deficient in ADHD. A feasibility trial of ONTRAC is being conducted in a resource limited clinical setting in New Delhi, India and is an exemplar of hi-tech global psychiatry. PMID- 24225016 TI - Evidence that a tax on sugar sweetened beverages reduces the obesity rate: a meta analysis. AB - BACKGROUND: Excess intake of sugar sweetened beverages (SSBs) has been shown to result in weight gain. To address the growing epidemic of obesity, one option is to combine programmes that target individual behaviour change with a fiscal policy such as excise tax on SSBs. This study evaluates the literature on SSB taxes or price increases, and their potential impact on consumption levels, obesity, overweight and body mass index (BMI). The possibility of switching to alternative drinks is also considered. METHODS: The following databases were used: Pubmed/Medline, The Cochrane Database of Systematic Reviews, Google Scholar, Econlit, National Bureau of Economics Research (NBER), Research Papers in Economics (RePEc). Articles published between January 2000 and January 2013, which reported changes in diet or BMI, overweight and/or obesity due to a tax on, or price change of, SSBs were included. RESULTS: Nine articles met the criteria for the meta-analysis. Six were from the USA and one each from Mexico, Brazil and France. All showed negative own-price elasticity, which means that higher prices are associated with a lower demand for SSBs. Pooled own price-elasticity was 1.299 (95% CI: -1.089 - -1.509). Four articles reported cross-price elasticities, three from the USA and one from Mexico; higher prices for SSBs were associated with an increased demand for alternative beverages such as fruit juice (0.388, 95% CI: 0.009 - 0.767) and milk (0.129, 95% CI: -0.085 - 0.342), and a reduced demand for diet drinks (-0.423, 95% CI: -0.628 - -1.219). Six articles from the USA showed that a higher price could also lead to a decrease in BMI, and decrease the prevalence of overweight and obesity. CONCLUSIONS: Taxing SSBs may reduce obesity. Future research should estimate price elasticities in low- and middle income countries and identify potential health gains and the wider impact on jobs, monetary savings to the health sector, implementation costs and government revenue. Context-specific cost-effectiveness studies would allow policy makers to weigh these factors. PMID- 24225017 TI - Mature cytotoxic CD56(bright)/CD16(+) natural killer cells can infiltrate lymph nodes adjacent to metastatic melanoma. AB - Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56(bright) NK cells among CD45(+) hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56(bright)CD16(+) NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node positive melanoma. PMID- 24225018 TI - Spectrum of RB1 mutations identified in 403 retinoblastoma patients. AB - BACKGROUND: Retinoblastoma (RB) is a malignant, childhood tumour of the developing retina that occurs with an estimated frequency of 1 in 20 000. Identification of oncogenic mutations in the RB1 gene aids in the clinical management of families with a heritable predisposition to RB. Here we present the spectrum of genetic and epigenetic changes identified in 194 tumours and 209 blood samples, from 403 unrelated RB patients. METHODS: Mutation screening was carried out across all 27 RB1 exons and their associated splice sites. Small coding sequence changes were detected using fluorescent conformation analysis followed by sequencing. Large exonic deletions were detected by quantitative fluorescent PCR. Methylation specific PCR of the RB1 promoter was performed to detect epigenetic alterations. Polymorphism analysis was used to determine loss of heterozygosity in tumour samples. RESULTS: 95% of the expected mutations were identified in the tumour samples, with 16 samples exhibiting only one mutation, while two samples had no detectable RB1 mutation. 96% of bilateral/familial RB blood samples and 9.5% of unilateral sporadic blood samples, yielded mutations. 111 were novel mutations. CONCLUSIONS: The full range of screening techniques is required to achieve a high screening sensitivity in RB patients. PMID- 24225019 TI - PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. AB - Poly(ADP-ribose)polymerase inhibitors (PARPis) have shown promising activity in patients with BRCA1/2 mutation-associated (BRCA1/2(MUT+)) ovarian and breast cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of sporadic high-grade serous ovarian cancer, and cancers defective in DNA repair pathways, such as prostate, endometrial, and pancreatic cancers. Several PARPis are currently in phase 1/2 clinical investigation, with registration trials now being designed. Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. Understanding more about the molecular abnormalities involved in BRCA-like tumors, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers, is critical to rapidly advancing the field of PARPi therapy and improve clinical outcomes. PMID- 24225020 TI - In vitro inhibition of mumps virus by retinoids. AB - BACKGROUND: Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeV in vitro. METHODS: Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot. RESULTS: The current work demonstrates that retinoids inhibit MuV in vitro due to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours. CONCLUSIONS: These results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection. PMID- 24225021 TI - Dopaminergic tone regulates transient potassium current maximal conductance through a translational mechanism requiring D1Rs, cAMP/PKA, Erk and mTOR. AB - BACKGROUND: Dopamine (DA) can produce divergent effects at different time scales. DA has opposing immediate and long-term effects on the transient potassium current (IA) within neurons of the pyloric network, in the Panulirus interruptus stomatogastric ganglion. The lateral pyloric neuron (LP) expresses type 1 DA receptors (D1Rs). A 10 min application of 5-100 MUM DA decreases LP IA by producing a decrease in IA maximal conductance (Gmax) and a depolarizing shift in IA voltage dependence through a cAMP-Protein kinase A (PKA) dependent mechanism. Alternatively, a 1 hr application of DA (>=5 nM) generates a persistent (measured 4 hr after DA washout) increase in IA Gmax in the same neuron, through a mechanistic target of rapamycin (mTOR) dependent translational mechanism. We examined the dose, time and protein dependencies of the persistent DA effect. RESULTS: We found that disrupting normal modulatory tone decreased LP IA. Addition of 500 pM-5 nM DA to the saline for 1 hr prevented this decrease, and in the case of a 5 nM DA application, the effect was sustained for >4 hrs after DA removal. To determine if increased cAMP mediated the persistent effect of 5nM DA, we applied the cAMP analog, 8-bromo-cAMP alone or with rapamycin for 1 hr, followed by wash and TEVC. 8-bromo-cAMP induced an increase in IA Gmax, which was blocked by rapamycin. Next we tested the roles of PKA and guanine exchange factor protein activated by cAMP (ePACs) in the DA-induced persistent change in IA using the PKA specific antagonist Rp-cAMP and the ePAC specific agonist 8-pCPT-2'-O-Me cAMP. The PKA antagonist blocked the DA induced increases in LP IA Gmax, whereas the ePAC agonist did not induce an increase in LP IA Gmax. Finally we tested whether extracellular signal regulated kinase (Erk) activity was necessary for the persistent effect by co-application of Erk antagonists PD98059 or U0126 with DA. Erk antagonism blocked the DA induced persistent increase in LP IA. CONCLUSIONS: These data suggest that dopaminergic tone regulates ion channel density in a concentration and time dependent manner. The D1R- PKA axis, along with Erk and mTOR are necessary for the persistent increase in LP IA induced by high affinity D1Rs. PMID- 24225022 TI - A structural explanation of the effects of dissociated glucocorticoids on glucocorticoid receptor transactivation. AB - There is a therapeutic need for glucocorticoid receptor (GR) ligands that distinguish between the transrepression and transactivation activity of the GR, the later thought to be responsible for side effects. These ligands are known as "dissociated glucocorticoids" (dGCs). The first published dGCs, RU24782 (9alpha fluoro-11beta-hydroxy-16alpha-methylpregna-21-thiomethyl-1,4-diene-3,20-dione) and RU24858 (9alpha-fluoro-11beta-hydroxy-16alpha-methylpregna-21-cyanide-1,4 diene-3,20-dione), do not have the 17alpha-hydroxyl group that characterizes dexamethasone (Dex; 9alpha-fluoro-11beta,17alpha,21-trihydroxy-16alpha methylpregna-1,4-diene-3,20-dione), and they differ from one another by having C21-thiomethyl and C21-cyanide moieties, respectively. Our aim was therefore to establish the structural basis of their activity. Both RU24782 and RU24858 induced a transactivation activity highly dependent on the GR expression level but always lower than dexamethasone. They also display less ability than dexamethasone to trigger steroid receptor coactivator 1 (SRC-1) recruitment and histone H3 acetylation. Docking studies, validated by mutagenesis experiments, revealed that dGCs are not anchored by Gln642, in contrast to Dex, which is hydrogen bonded to this residue via its 17alpha-hydroxyl group. This contact is essential for SRC-1 recruitment and subsequent dexamethasone-induced GR transactivation, but not transrepression. The ability of dGCs to make contacts with Ile747, for both RU24858 and RU24782 and with Asn564 for RU24858 are not strong enough to maintain GR in a conformation able to efficiently recruit SRC-1, unless SRC-1 is overexpressed. Overall, our findings provide some structural guidelines for the synthesis of potential new dissociated glucocorticoids with a better therapeutic ratio. PMID- 24225023 TI - Is reactivation of toxoplasmic retinochoroiditis associated to increased annual rainfall? AB - BACKGROUND: Reactivation of toxoplasmic retinochoroiditis is the most frequent form of uveitis in Misiones, Argentina. Fluctuations in the number of patients consulting with this type of uveitis were detected during the last decade. Since the province was consecutively exposed to rainy and dry periods over the last years, we decided to explore whether a relationship between reactivation of toxoplasmic retinochoroiditis and rain might be established according to the data registered during the 2004-2010 period. RESULTS: The frequency of toxoplasmic reactivation episodes increases when precipitation increases (mostly in second and fourth trimesters of each year). Analysis of the independent variables demonstrates that precipitation is a significant predictor of the frequency of reactivation episodes. Although registered toxoplasmic reactivations were more frequent during the third trimester of the year, the association between the third trimester and the reactivation episodes did not reach statistical significance. CONCLUSION: Prolonged and intense rainfall periods were significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition on both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities are discussed. PMID- 24225024 TI - Insight into the HIV-1 Vif SOCS-box-ElonginBC interaction. AB - The HIV-1 viral infectivity factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/Cullin5 containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis. The suppressors-of-cytokine-signalling-like domain (SOCS-box) of HIV 1 Vif is essential for E3 ligase engagement, and contains a BC box as well as an unusual proline-rich motif. Here, we report the NMR solution structure of the Vif SOCS-ElonginBC (EloBC) complex. In contrast to SOCS-boxes described in other proteins, the HIV-1 Vif SOCS-box contains only one alpha-helical domain followed by a beta-sheet fold. The SOCS-box of Vif binds primarily to EloC by hydrophobic interactions. The functionally essential proline-rich motif mediates a direct but weak interaction with residues 101-104 of EloB, inducing a conformational change from an unstructured state to a structured state. The structure of the complex and biophysical studies provide detailed insight into the function of Vif's proline-rich motif and reveal novel dynamic information on the Vif-EloBC interaction. PMID- 24225026 TI - Pseudomonas kunmingensis sp. nov., an exopolysaccharide-producing bacterium isolated from a phosphate mine. AB - A Gram-stain-negative, rod-shaped, exopolysaccharide-producing, strictly aerobic bacterium with a single polar flagellum, designated strain HL22-2(T), was isolated from a phosphate mine situated in a suburb of Kunmming in Yunnan province in south-western China. The taxonomic status of this strain was evaluated by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HL22-2(T) was related to members of the genus Pseudomonas. 16S rRNA gene sequence similarities between strain HL22-2(T) and Pseudomonas xanthomarina KMM 1447(T), Pseudomonas alcaliphila AL15-21(T) and Pseudomonas stutzeri ATCC 17588(T) were 98.9, 98.10% and 98.06%, respectively. The major cellular fatty acids were C(18 : 1)omega7c, C(16 : 0) and summed feature 3 (C(16 : 1)omega7c and/or C(16 : 1)omega6c). The DNA G+C content was 60.3 mol%. On the basis of phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness values, strain HL22-2(T) represents a novel species of the genus Pseudomonas, for which the name Pseudomonas kunmingensis sp. nov. is proposed. The type strain is HL22-2(T) ( = CGMCC 1.12273(T) = DSM 25974(T)). PMID- 24225025 TI - Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down regulating cholesterol synthesis and altering detergent resistant membranes composition. AB - BACKGROUND: The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors. METHODS: We studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells. RESULTS: MDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells. CONCLUSIONS: Our work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells. PMID- 24225027 TI - Dickeya solani sp. nov., a pectinolytic plant-pathogenic bacterium isolated from potato (Solanum tuberosum). AB - Pectinolytic bacteria have been recently isolated from diseased potato plants exhibiting blackleg and slow wilt symptoms found in a number of European countries and Israel. These Gram-reaction-negative, motile, rods were identified as belonging to the genus Dickeya, previously the Pectobacterium chrysanthemi complex (Erwinia chrysanthemi), on the basis of production of a PCR product with the pelADE primers, 16S rRNA gene sequence analysis, fatty acid methyl esterase analysis, the production of phosphatases and the ability to produce indole and acids from alpha-methylglucoside. Differential physiological assays used previously to differentiate between strains of E. chrysanthemi, showed that these isolates belonged to biovar 3. Eight of the isolates, seven from potato and one from hyacinth, were analysed together with 21 reference strains representing all currently recognized taxa within the genus Dickeya. The novel isolates formed a distinct genetic clade in multilocus sequence analysis (MLSA) using concatenated sequences of the intergenic spacer (IGS), as well as dnaX, recA, dnaN, fusA, gapA, purA, rplB, rpoS and gyrA. Characterization by whole-cell MALDI-TOF mass spectrometry, pulsed field gel electrophoresis after digestion of whole-genome DNA with rare-cutting restriction enzymes, average nucleotide identity analysis and DNA-DNA hybridization studies, showed that although related to Dickeya dadantii, these isolates represent a novel species within the genus Dickeya, for which the name Dickeya solani sp. nov. (type strain IPO 2222(T) = LMG25993(T) = NCPPB4479(T)) is proposed. PMID- 24225028 TI - Transitions in endocrinology: treatment of Turner's syndrome during transition. AB - Transition in health care for young patients with Turner's syndrome (TS) should be perceived as a staged but uninterrupted process starting in adolescence and moving into adulthood. As a condition associated with high risk of short stature, cardiovascular diseases, ovarian failure, hearing loss and hypothyroidism, TS requires the attention of a multidisciplinary team. In this review paper, we systematically searched the relevant literature from the last decade to discuss the array of problems faced by TS patients and to outline their optimal management during the time of transfer to adult service. The literature search identified 233 potentially relevant articles of which 114 were analysed. The analysis confirmed that all medical problems present during childhood should also be followed in adult life. Additionally, screening for hypertension, diabetes mellitus, dyslipidaemia, and osteoporosis is needed. After discharge from the paediatric clinic, there is still a long way to go. PMID- 24225029 TI - Decreased prevalence of hypercholesterolaemia and stabilisation of obesity trends in 5-year-old children: possible effects of changed public health policies. AB - BACKGROUND: Overweight/obesity in children is a worldwide public health problem. Together with hypercholesterolaemia they are associated with early atherosclerotic complications. OBJECTIVES: In this study, we aimed to investigate the anthropometric characteristics and total cholesterol (TC) levels in a population of 5-year-old children, to determine trends in the prevalence of overweight/obesity and hypercholesterolaemia in 5-year-old children over a period of 8 years (2001-2009) and to assess the impact of modified national nutritional guidelines for kindergartens implemented in 2005. DESIGN: Cross-sectional studies of overweight/obesity prevalence in the years 2001, 2003-2005 and 2009, and hypercholesterolaemia in years 2001 and 2009, in 5-year-old children. SUBJECTS: Altogether, 12 832 (6308 girls/6524 boys) children were included. METHODS: Overweight/obesity was defined by IOTF criteria. Hypercholesterolaemia was defined by TC level >5 mmol/l. Multivariable logistic regression models were used. RESULTS: NO CORRELATION BETWEEN BMI VALUES AND TC LEVELS WAS FOUND. OVERWEIGHT AND OBESITY PREVALENCE WERE STABILISED FROM 2001 TO 2009 (ODDS RATIO (OR) (95% CI): 1.13 (0.99-1.3) and 1.13 (0.89-1.42) respectively). Girls were more frequently overweight/obese than boys (OR (95% CI): 0.71 (0.65-0.79) and 0.75 (0.64-0.89) respectively). Prevalence of hypercholesterolaemia significantly decreased from 2001 to 2009 (OR (95% CI): 0.47 (0.41-0.55)). It was less frequent in boys than in girls (OR (95% CI): O.7 (0.61-0.8)). CONCLUSIONS: This is the first study to describe a negative trend in the prevalence of hypercholesterolaemia in pre-pubertal children. In addition, the prevalence of overweight/obesity in these children has been stabilised. Nationwide changes in public health policies could have influenced these observations. PMID- 24225031 TI - How Patient Interactions With a Computer-Based Video Intervention Affect Decisions to Test for HIV. AB - The current study examines predictors of HIV test acceptance among emergency department patients who received an educational video intervention designed to increase HIV testing. A total of 202 patients in the main treatment areas of a high-volume, urban hospital emergency department used inexpensive netbook computers to watch brief educational videos about HIV testing and respond to pre postintervention data collection instruments. After the intervention, computers asked participants if they would like an HIV test: Approximately 43% (n = 86) accepted. Participants who accepted HIV tests at the end of the intervention took longer to respond to postintervention questions, which included the offer of an HIV test, F(1, 195) = 37.72, p < .001, compared with participants who did not accept testing. Participants who incorrectly answered pretest questions about HIV symptoms were more likely to accept testing F(14, 201) = 4.48, p < .001. White participants were less likely to accept tests than Black, Latino, or "Other" patients, chi(2)(3, N = 202) = 10.39, p < .05. Time spent responding to postintervention questions emerged as the strongest predictor of HIV testing, suggesting that patients who agreed to test spent more time thinking about their response to the offer of an HIV test. Examining intervention usage data, pretest knowledge deficits, and patient demographics can potentially inform more effective behavioral health interventions for underserved populations in clinical settings. PMID- 24225030 TI - Replication characteristics of swine influenza viruses in precision-cut lung slices reflect the virulence properties of the viruses. AB - Precision-cut lung slices of pigs were infected with five swine influenza A viruses of different subtypes (A/sw/Potsdam/15/1981 H1N1, A/sw/Bad Griesbach/IDT5604/2006 H1N1, A/sw/Bakum/1832/2000 H1N2, A/sw/Damme/IDT5673/2006 H3N2, A/sw/Herford/IDT5932/2007 H3N2). The viruses were able to infect ciliated and mucus-producing cells. The infection of well-differentiated respiratory epithelial cells by swine influenza A viruses was analyzed with respect to the kinetics of virus release into the supernatant. The highest titres were determined for H3N2/2006 and H3N2/2007 viruses. H1N1/1981 and H1N2/2000 viruses replicated somewhat slower than the H3N2 viruses whereas a H1N1 strain from 2006 multiplied at significantly lower titres than the other strains. Regarding their ability to induce a ciliostatic effect, the two H3N2 strains were found to be most virulent. H1N1/1981 and H1N2/2000 were somewhat less virulent with respect to their effect on ciliary activity. The lowest ciliostatic effect was observed with H1N1/2006. In order to investigate whether this finding is associated with a corresponding virulence in the host, pigs were infected experimentally with H3N2/2006, H1N2/2000, H1N1/1981 and H1N1/2006 viruses. The H1N1/2006 virus was significantly less virulent than the other viruses in pigs which was in agreement with the results obtained by the in vitro-studies. These findings offer the possibility to develop an ex vivo-system that is able to assess virulence of swine influenza A viruses. PMID- 24225032 TI - Prediction of injury by limited and asymmetrical fundamental movement patterns in american football players. AB - CONTEXT: Previous injury is the strongest risk factor for future injury in sports. It has been proposed that motor-control changes such as movement limitation and asymmetry associated with injury and pain may be perpetuated as part of an individual's movement strategy. Motor control of fundamental 1-*-body weight tasks can reliably and efficiently be measured in the field. OBJECTIVE: To determine whether the motor control of fundamental movement patterns and pattern asymmetry have a relationship with time-loss injury over the course of the preseason in professional football. DESIGN: Injury-risk study. SETTING: American professional football facilities. PARTICIPANTS: 238 American professional football players. INTERVENTION: To measure the motor control of 1-*-body-weight fundamental movement patterns, Functional Movement Screen scores were obtained before the start of training camp. The previously established cutoff score of <=14 and the presence of any asymmetries on the FMS were examined using relative risk to determine if a relationship exists with time-loss injury. MAIN OUTCOME MEASURE: Time-loss musculoskeletal injury defined as any time loss from practice or competition due to musculoskeletal injury. RESULTS: Players who scored <=14 exhibited a relative risk of 1.87 (CI95 1.202.96). Similarly, players with at least 1 asymmetry displayed a relative risk of 1.80 (CI95 1.112.74). The combination of scoring below the threshold and exhibiting a movement asymmetry was highly specific for injury, with a specificity of .87 (CI95 .84.90). CONCLUSION: The results of this study suggest that fundamental movement patterns and pattern asymmetry are identifiable risk factors for time-loss injury during the preseason in professional football players. PMID- 24225033 TI - Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. AB - PURPOSE: Sodium nitrite, a food additive that is used as a color fixative and preservative for meats and fish, has been reported to have adverse health effects due to increased oxidative stress that could be harmful to different organs including the liver. Meanwhile, silymarin protects against hepatotoxicity caused by a variety of agents, on account of its antioxidative and anti-inflammatory effects. We therefore examined the impact of dietary silymarin on sodium nitrite induced liver damage in rats. METHODS: Fifty adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite in the presence or absence of silymarin (10 and 25 mg/kg). Hepatic proinflammatory cytokines (TNF-alpha and IL-1beta), hepatic fibrosis marker (MCP-1 and TGF-beta1), mitochondrial activity marker (cytochrome C oxidase) and c-reactive protein (CRP) levels were measured. Hepatic apoptosis was assessed through determination of caspase-3 activity and DNA fragmentation. RESULTS: We found that oral sodium nitrite enhanced oxidative stress with subsequent increases in TNF-alpha (2-fold), IL-1beta (4-fold), MCP-1 (4-fold), TGF-beta1 (3-fold) and CRP (4-fold). In addition, sodium nitrite brings about reduced cytochrome C oxidase and enhanced caspase-3 activity and DNA fragmentation. Daily treatment with silymarin markedly ameliorated all these effects. CONCLUSIONS: Silymarin ameliorated the impairment of hepatic function in rats that had ingested sodium nitrite. Silymarn possesses antioxidant, anti inflammatory, antifibrotic and anti-apoptotic effects. PMID- 24225034 TI - Understanding consumer acceptance of intervention strategies for healthy food choices: a qualitative study. AB - BACKGROUND: The increasing prevalence of overweight and obesity poses a major threat to public health. Intervention strategies for healthy food choices potentially reduce obesity rates. Reviews of the effectiveness of interventions, however, show mixed results. To maximise effectiveness, interventions need to be accepted by consumers. The aim of the present study is to explore consumer acceptance of intervention strategies for low-calorie food choices. Beliefs that are associated with consumer acceptance are identified. METHODS: Data was collected in the Netherlands in 8 semi-structured interviews and 4 focus group discussions (N = 39). Nine archetypical strategies representing educational, marketing and legal interventions served as reference points. Verbatim transcriptions were coded both inductively and deductively with the framework approach. RESULTS: We found that three beliefs are related to consumer acceptance: 1) general beliefs regarding obesity, such as who is responsible for food choice; 2) the perceived effectiveness of interventions; and 3) the perceived fairness of interventions. Furthermore, the different aspects underlying these general and intervention-specific beliefs were identified. CONCLUSIONS: General and intervention-specific beliefs are associated with consumer acceptance of interventions for low-calorie food choices. Policymakers in the food domain can use the findings to negotiate the development of interventions and to assess the feasibility of interventions. With respect to future research, we recommend that segments of consumers based on perceptions of intervention strategies are identified. PMID- 24225035 TI - Effects of tea saponin on glucan conversion and bonding behaviour of cellulolytic enzymes during enzymatic hydrolysis of corncob residue with high lignin content. AB - BACKGROUND: Recently, interest in the utilization of corncob residue (CCR, with high lignin of 45.1%) as a feedstock for bioethanol has been growing. Surfactants have been one of the most popular additives intended to prevent the inhibitory effect of lignin on cellulolytic enzymes, thereby improving hydrolysis. In this study, the effects of biosurfactant tea saponin (TS) on the enzymatic hydrolysis of CCR and the bonding behavior of cellulolytic enzymes to the substrate were investigated. The surface tension in the supernatant was also detected to obtain information about the characteristics and stability of TS. RESULTS: The glucose concentration was 17.15 mg/mL at 120 hours of hydrolysis with the low loading of cellulolytic enzymes (7.0 FPU/g cellulose and 10.5 BGU/g cellulose) and 5% CCR. The optimal dosage of TS was its critical micelle concentration (cmc, 1.80 mg/mL). The glucose yield was enhanced from 34.29 to 46.28 g/100 g dry matter by TS. The results indicate that TS can promote the adsorption of cellulolytic enzymes on the substrate and mediate the release of adsorbed enzymes. Meanwhile, TS improves the recovery of the cellulolytic enzymes after a hydrolysis cycle and prevents deactivation of the enzymes during the intense shaking process. The surface tension in supernatants of digested CCR with TS remained at 50.00 mN/m during the course of hydrolysis. It is interesting to note that biosurfactant TS can maintain the surface tension in supernatants, despite its digestibility by cellulolytic enzymes. CONCLUSIONS: Serving as an accelerant of lignocellulose hydrolysis, TS can also be degraded by the cellulolytic enzymes and release glucose while retaining stability, which reduces the cost of both the cellulolytic enzymes and the additive. As the glucose from the TS could be utilized by yeast, further efforts will investigate the mechanism of function and the application of TS in the production of ethanol by simultaneous saccharification and fermentation (SSF). PMID- 24225036 TI - Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status. AB - Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID- 24225038 TI - Bartholin's gland hyperplasia. Case report and a review of literature. AB - BACKGROUND: Tumors arising from glands of the female ano-genital area, such as minor and major vestibular glands, are very rare. Lesions affecting Bartholin's gland can be divided into two groups: benign and malignant lesions. In the first group we can include nodular hyperplasia, adenoma, adenomioma which can sometimes cause Bartholin's gland enlargement and difficult differential diagnosis. Surgery is considered the treatment of choice, frequently represented by marsupialization with rates of local recurrence. CASE REPORT: We describe a case of a 50-year-old woman with a several-years history of recurrent episodes of Bartholinitis, previously treated with marsupialization. Patient underwent complete excision of the left Bartholin's gland without operative complications. Pathological findings showed a Bartholin's gland hyperplasia. Post-operative course was regular, free from surgical complications. After one year, the patient is free from any local disease. RESULTS AND CONCLUSION: In women in postmenopausal age, in those cases in which marsupialization doesn't lead to an improvement in symptomatology and in those cases in which, at physical examination, Bartholin's gland enlargement appeared to be firm and irregular, because of the higher incidence of malignancy in these situations, total excision of the gland is recommended. Total excision of the Bartholin's Gland is a safe technique, given the low incidence of procedure- related morbilities. We do not consider biopsy of the gland a proper strategy for the high percentage of false negative results. PMID- 24225037 TI - Stress susceptibility-specific phenotype associated with different hippocampal transcriptomic responses to chronic tricyclic antidepressant treatment in mice. AB - BACKGROUND: The effects of chronic treatment with tricyclic antidepressant (desipramine, DMI) on the hippocampal transcriptome in mice displaying high and low swim stress-induced analgesia (HA and LA lines) were studied. These mice displayed different depression-like behavioral responses to DMI: stress-sensitive HA animals responded to DMI, while LA animals did not. RESULTS: To investigate the effects of DMI treatment on gene expression profiling, whole-genome Illumina Expression BeadChip arrays and qPCR were used. Total RNA isolated from hippocampi was used. Expression profiling was then performed and data were analyzed bioinformatically to assess the influence of stress susceptibility-specific phenotypes on hippocampal transcriptomic responses to chronic DMI. DMI treatment affected the expression of 71 genes in HA mice and 41 genes in LA mice. We observed the upregulation of Igf2 and the genes involved in neurogenesis (HA: Sema3f, Ntng1, Gbx2, Efna5, and Rora; LA: Otx2, Rarb, and Drd1a) in both mouse lines. In HA mice, we observed the upregulation of genes involved in neurotransmitter transport, the termination of GABA and glycine activity (Slc6a11, Slc6a9), glutamate uptake (Slc17a6), and the downregulation of neuropeptide Y (Npy) and corticotropin releasing hormone-binding protein (Crhbp). In LA mice, we also observed the upregulation of other genes involved in neuroprotection (Ttr, Igfbp2, Prlr) and the downregulation of genes involved in calcium signaling and ion binding (Adcy1, Cckbr, Myl4, Slu7, Scrp1, Zfp330). CONCLUSIONS: Several antidepressant treatment responses are similar in individuals with different sensitivities to stress, including the upregulation of Igf2 and the genes involved in neurogenesis. However, the findings also reveal that many responses to antidepressant treatments, involving the action of individual genes engaged in neurogenesis, neurotransmitter transport and neuroprotection, depend on constitutive hippocampal transcriptomic profiles and might be genotype dependent. The results suggest that, when and if this becomes feasible, antidepressant treatment should take into consideration individual sensitivity to stress. PMID- 24225039 TI - Role of non-invasive assessment in prediction of preclinical cardiac affection in multi-transfused thalassaemia major patients. AB - BACKGROUND: The principal cause of mortality and morbidity in beta-thalassemia major (beta-TM) is the iron overload as these patients receive about 20 times the normal intake of iron, which leads to iron accumulation and damage in the liver, heart, and endocrine organs. Chronically transfused patients used to die from cardiac iron overload in their teens and twenties. Monitoring of iron status through cardiac magnetic resonance imaging (CMRI) has replaced the conventional methods of assessment, yet this modality is not readily available in centers where the disease distribution is maximal. Objectives The aim of this work is to study some simple non-invasive tools and their abilities to predict preclinical cardiac affection reflecting cardiac iron deposition (CID) in multi-transfused beta-TM patients taking the T2* CMRI as a gold standard reference test. METHODS: One hundred consecutive multi-transfused, clinically stable beta-TM patients with age ranging from 16 to 30 years (mean +/- SD, 21.1 +/- 3.9) were included in this study. Assessment of serum ferritin, serum hepcidin, and high-sensitivity C reactive protein as well as cardiac assessment by echo-doppler and 24-hour Holter were used to predict CID, and consequently predict preclinical cardiac affection, in reference to CMRI results as the standard method of cardiac iron assessment. RESULTS: According to CMRI results, patients were subdivided into a group of 42 patients with detectable myocardial iron (T*<= 20 ms) and a group of 58 patients with no detectable myocardial iron (T* > 20 ms). No differences in age, gender, or distribution of splenectomized patients were observed between both groups. Patients with detectable myocardial iron received significantly higher number of transfusions per year than those with no detectable myocardial iron (mean +/- SD, 14.6 +/- 1.7 vs. 12.5 +/- 1.7; P < 0.001) yet comparable levels of serum ferritin, serum hepcidin, and hepcidin/ferritin ratio (P > 0.05) were noted. Cardiac iron detection was associated with significantly lower heart rate (mean +/- SD, 75 +/- 6.1 vs. 80 +/- 6.9; P < 0.001), lower left ventricular ejection fraction (LVEF) (mean +/- SD 60.1 +/- 3.2 vs. 70.1 +/- 2.8; P < 0.001), and higher total number of premature ventricular contractions (PVCs) (median 78 vs. 14; P < 0.001). The group with CID comprised significantly more patients with left ventricular diastolic dysfunction (15/42, 35.7% vs. 3/58, 5.2%; P < 0.001); PVCs >=10/hour (13/42, 31% vs. 2/58, 3.4%; P < 0.001); episodes of sinus pauses (6/42, 14.3% vs. 1/58, 1.7%; P < 0.05); episodes of high-grade atrio-ventricular block (5/42, 11.9% vs. 1/58, 1.7%; P < 0.05) compared to the group with no (CID). In presence of normal LVEF, detection of 10 or more PVCs per hour was the most predictive of cardiac iron loading with a positive predictive value of 86.7% and specificity of 96.6%, and the highest likelihood ratio (9.09). Detection of more than 22 PVCs/24 hours had the best sensitivity (81%) and the best negative predictive value (84%). The positive likelihood ratio of the studied parameters was highest in case of presence of PVCs >=10/hour and lowest in case of average heart rate with a cut-off level of <=77.5 bpm (9.09 and 1.46, respectively). CONCLUSION: Our results support our hypothesis that monitoring beta-TM patients with echo and Holter electrocardiogram can help in the detection of preclinical cardiac affection in centers lacking cardiac MRI; however, due to relatively low sensitivity they can not fully replace CMRI. Further work is needed to identify additional simple parameters that can form a diagnostic model with adequate sensitivity. PMID- 24225040 TI - [Adherence to medication and epilepsy: a current issue]. AB - As in other chronic diseases, adherence to medication in epilepsy is critical for seizure control. Its assessment remains challenging in research as in clinical practice. Recent evidences showed another face of nonadherence: the overconsumption of antiepileptic drugs. Some educational interventions with easy implementation were found to be effective in improving adherence and should be therefore more used in everyday practice. PMID- 24225041 TI - [Generic drugs and the consumption trends of antihypertensives in Morocco]. AB - BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population. PMID- 24225042 TI - [Is there any interest to dose the azathioprine's metabolites during inflammatory bowel diseases?]. AB - OBJECTIVE: The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. METHOD: We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1 year. Each patient had a dosage of azathioprine metabolites. RESULTS: We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. CONCLUSION: Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule. PMID- 24225043 TI - [Sulfasalazine-induced DRESS syndrome associated with Epstein Barr virus reactivation]. PMID- 24225044 TI - [Tachycardia and precordial pain with agomelatine: a case report]. PMID- 24225045 TI - [Pityriasis rosea-like adverse reaction induced by pristinamycine]. PMID- 24225046 TI - [Microscopic colitis in a patient treated with duloxetine]. PMID- 24225047 TI - [Cytolysis in an elderly patient treated with dabigatran etexilate]. PMID- 24225048 TI - The post-activation potentiation effect on squat jump performance: age and sex effect. AB - This study examined the post-activation potentiation (PAP) effects on squat jump (SJ) performance and on peak rate of force development (RFDpeak) in preadolescent (10-12 y), adolescents (14-15 y) and adults (20-25 y) males and females. All participants performed a SJ with and without prior conditioning stimulus (PAP and control protocol, respectively), consisting of 3 * 3-second maximal isometric squats. Jump height and RFDpeak of the vertical ground reaction force during SJ were assessed before, and at 20 seconds and at 4 minutes following the conditioning stimulus. The results revealed a different pattern of age-effect on SJ performance within males and females. The RFDpeak significantly increased as a factor of age in both males and females (P < .05). Increase in SJ performance after conditioning stimulus occurred only in men (P < .05), with no effects in teen-males, boys, and female groups. There was a significant PAP effect on RFDpeak in both adult groups (P < .05) and teen-males, with no effects in children. In conclusion, the PAP effects on SJ performance and RFDpeak are age- and sex-dependent; that is PAP appears as a viable method for acutely enhancing SJ performance in men but not in pediatric population. PMID- 24225049 TI - Inhibition of keratinocyte proliferation by phospholipid-conjugates of a TLR7 ligand in a Myc-induced hyperplastic actinic keratosis model in the absence of systemic side effects. AB - BACKGROUND: The Toll-like receptor 7 (TLR7) activator imiquimod (IMQ) is safe and effective in treating actinic keratosis; however, an intermittent treatment regimen is necessary because of excessive local reactions. OBJECTIVES: To evaluate in vitro potency, pharmacodynamics/pharmacokinetics, toxicity and efficacy in vivo of the newly developed TLR7 ligand-phospholipid conjugate, TMX 202, in a gel formulation. MATERIAL AND METHODS: The effects of TMX-202 were assessed both in vitro on a murine macrophage cell line and in primary bone marrow-derived dendritic cells and in vivo on mice (C57BL/6-wild type, Myd88(-/-) and Tlr7(-/-)). RESULTS: TMX-202 was more potent than IMQ in vitro using murine and human cells. In contrast, in vivo it showed less systemic pro-inflammatory activity and better safety than IMQ. Moreover, the TMX-202 gel formulation exhibited at least comparable efficacy to Aldara in a mouse model for skin proliferative diseases. CONCLUSION: TMX-202 is safe and efficacious without causing excessive adverse effects, suggesting that it may be an alternative to Aldara for the treatment of proliferative skin conditions. PMID- 24225050 TI - 3DScapeCS: application of three dimensional, parallel, dynamic network visualization in Cytoscape. AB - BACKGROUND: The exponential growth of gigantic biological data from various sources, such as protein-protein interaction (PPI), genome sequences scaffolding, Mass spectrometry (MS) molecular networking and metabolic flux, demands an efficient way for better visualization and interpretation beyond the conventional, two-dimensional visualization tools. RESULTS: We developed a 3D Cytoscape Client/Server (3DScapeCS) plugin, which adopted Cytoscape in interpreting different types of data, and UbiGraph for three-dimensional visualization. The extra dimension is useful in accommodating, visualizing, and distinguishing large-scale networks with multiple crossed connections in five case studies. CONCLUSIONS: Evaluation on several experimental data using 3DScapeCS and its special features, including multilevel graph layout, time course data animation, and parallel visualization has proven its usefulness in visualizing complex data and help to make insightful conclusions. PMID- 24225051 TI - Evaluation of health related quality of life in children with immune thrombocytopenia with the PedsQLTM 4.0 Generic Core Scales: a study on behalf of the pays de Loire pediatric hematology network. AB - BACKGROUND: Immune thrombocytopenia (ITP) is a childhood disorder that is often life-altering for children and their parents. Health related quality of life (HRQL) has never been chronologically monitored in children with ITP. We initiated a prospective study to assess HRQL from diagnosis to six months and define factors that influence this outcome in children with ITP. METHODS: 73 children with acute ITP aged from 2 to 18 years were prospectively enrolled in the study. According to the presence of bleeding, they were or were not given a 4 day course of corticosteroid treatment. The PedsQLTM 4.0 Generic Core Scale was completed by children and parents upon their inclusion in the study and 6 months after diagnosis. RESULTS: Over the six month period, quality of life improved in terms of their global, physical and psychosocial well-being for 54.5%, 35.6% and 36.2% of patients respectively. This improvement is clinically relevant compared to scores at diagnosis, corresponding at least to a minimal clinically important difference (MCID). Factors such as sex, age, platelet count, bleeding scores, bone marrow aspiration and persistence of ITP at 6 months were not significantly associated with HRQL scores. However, preceding viral infection was identified to have an impact on HRQL. CONCLUSIONS: This first longitudinal study assessing HRQL in children with ITP reveals a global improvement in PedSQLTM 4.0. However, these results should be considered with caution since our data also confirm that self report HRQL scores are not influenced by any analyzed biologic or clinical parameters. Others tools, such as Kids' ITP Tools, would probably be required to assess the HRQL of this population. TRIAL REGISTRATION: Trial registration clinical trials.gov Identifier: NCT00331357. PMID- 24225052 TI - Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients. AB - BACKGROUND: The p.Leu1077Pro CFTR mutation was firstly described in 1992 as a mild allele that confers a pancreatic sufficiency phenotype but the information collected in database CFTR2 lead to consider p.Leu1077Pro as a severe CF mutation. Although it is typical of Southern Italy, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area. The aim of our study was to describe prevalence and clinical features in patients bearing this mutation followed in our Cystic Fibrosis Centre to demonstrate that this mutation should be included in the mutation panel firstly tested in patients originated from Southern Italy. FINDINGS: We reviewed data from a cohort of 111 cystic fibrosis patients. 4 patients who were heterozygous for the p.Leu1077Pro mutation were included in the study.In our Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had positive sweat test values, pancreatic insufficiency and pulmonary exacerbations. One out of four patients even showed both FEV1 and FVC values significantly below the normal range, the presence of bronchiectasis and chronic Pseudomonas aeruginosa colonization. CONCLUSIONS: We found that the p.Leu1077Pro CFTR mutation is associated with a classic CF phenotype confirming what is reported in CFTR2 database. The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy. PMID- 24225053 TI - Effect of MWCNT size, carboxylation, and purification on in vitro and in vivo toxicity, inflammation and lung pathology. AB - BACKGROUND: Several properties of multi-walled carbon nanotubes (MWCNT) have the potential to affect their bioactivity. This study examined the in vitro and in vivo outcomes of the influence of diameter, length, purification and carboxylation (in vitro testing only) of MWCNT. METHODS: Three original 'as received' MWCNT that varied in size (diameter and length) were purified and functionalized by carboxylation. The resulting MWCNT were characterized and examined for cytotoxicity and inflammasome activation in vitro using THP-1 cells and primary alveolar macrophages from C57BL/6 mice. Oropharyngeal aspiration administration was used to deliver original MWCNT and in vivo bioactivity and lung retention was examined at 1 and 7 days. RESULTS: Studies with THP-1 macrophages demonstrated that increased length or diameter corresponded with increased bioactivity as measured by inflammasome activation. Purification had little effect on the original MWCNT, and functionalization completely eliminated bioactivity. Similar results were obtained using alveolar macrophages isolated from C57BL/6 mice. The in vivo studies demonstrated that all three original MWCNT caused similar neutrophil influx at one day, but increasing length or diameter resulted in the lavaged cells to release more inflammatory cytokines (IL-6, TNF alpha, and IL-1beta) ex vivo. Seven-day histology revealed that, consistent with the in vitro results, increasing width or length of MWCNT caused more severe pathology with the longest MWCNT causing the most severe inflammation. In addition, the same two larger MWCNT were retained more in the lung at 7 days. CONCLUSIONS: Taken together, the results indicated that in vitro and in vivo bioactivity of MWCNT increased with diameter and length. Purification had no significant modifying effect from the original MWCNT. Functionalization by carboxylation completely eliminated the bioactive potential of the MWCNT regardless of size in in vitro testing. PMID- 24225054 TI - The efficacy of dapagliflozin combined with hypoglycemic drugs in treating type 2 diabetes: protocol for meta-analysis of randomized controlled trials. AB - BACKGROUND: Dapagliflozin is a first-in-class oral sodium glucose co-transporter 2 (SGLT2) inhibitor. It is often used in combination with conventional anti diabetic drugs such as metformin, glimepiride, and insulin in treating type 2 diabetes (T2D). It not only reduces glucose reabsorption in the kidney but also increases renal glucose excretion. Some studies found the actions of dapagliflozin independent of insulin and free from risk of weight gain. This meta analysis aims to evaluate whether dapagliflozin is synergistic with other anti diabetic drugs without risk of weight gain. METHODS/DESIGN: This meta-analysis will include the randomized controlled trials (RCT) evaluating the efficacy of dapagliflozin as an add-on drug in treating T2D for >8 weeks with the outcome measures glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight. Information of relevant RCTs will be retrieved from major databases including PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Google Scholar according to a pre-specified search strategy. Google and manual search will find other unpublished reports and supplementary data. Eligible RCTs will be selected according to pre-specified inclusion and exclusion criteria. Data will be extracted and input into a pre-formatted spreadsheet. The Cochrane risk of bias tool will be used to assess the quality of the eligible RCTs. Meta-analysis based on the random-effects model will be conducted to compare the changes of HbA1c (%), FPG (mmol/L), and body weight (kg) between dapagliflozin arm and placebo arm. Publication bias will be evaluated with a funnel plot and the Egger's test. Heterogeneity will be assessed with the I2 statistics. Sensitivity analysis will be conducted on follow-up periods. The evidential quality of the findings will be assessed with the GRADE profiler. DISCUSSION: The findings of this meta-analysis will be important to clinicians, patients, and health policy makers regarding the use of dapagliflozin in T2D treatment. STUDY REGISTRATION: PROSPERO registration number: CRD42013005034. PMID- 24225055 TI - Twentieth anniversary of the European Union health mandate: taking stock of perceived achievements, failures and missed opportunities - a qualitative study. AB - BACKGROUND: The European Union (EU) health mandate was initially defined in the Maastricht Treaty in 1992. The twentieth anniversary of the Treaty offers a unique opportunity to take stock of EU health actions by giving an overview of influential public health related EU-level policy outputs and a summary of policy outputs or actions perceived as an achievement, a failure or a missed opportunity. METHODS: Semi-structured expert interviews (N = 20) were conducted focusing on EU-level actions that were relevant for health. Respondents were asked to name EU policies or actions that they perceived as an achievement, a failure or a missed opportunity. A directed content analysis approach was used to identify expert perceptions on achievements, failures and missed opportunities in the interviews. Additionally, a nominal group technique was applied to identify influential and public health relevant EU-level policy outputs. RESULTS: The ranking of influential policy outputs resulted in top positions of adjudications and legislations, agencies, European Commission (EC) programmes and strategies, official networks, cooperative structures and exchange efforts, the work on health determinants and uptake of scientific knowledge. The assessment of EU health policies as being an achievement, a failure or a missed opportunity was often characterized by diverging respondent views. Recurring topics that emerged were the Directorate General for Health and Consumers (DG SANCO), EU agencies, life style factors, internal market provisions as well as the EU Directive on patients' rights in cross-border healthcare. Among these recurring topics, expert perceptions on the establishment of DG SANCO, EU public health agencies, and successes in tobacco control were dominated by aspects of achievements. The implementation status of the Health in All Policy approach was perceived as a missed opportunity. CONCLUSIONS: When comparing the emerging themes from the interviews conducted with the responsibilities defined in the EU health mandate, one can identify that these responsibilities were only partly fulfilled or acknowledged by the respondents. In general, the EU is a recognized public health player in Europe which over the past two decades, has begun to develop competencies in supporting, coordinating and supplementing member state health actions. However, the assurance of health protection in other European policies seems to require further development. PMID- 24225057 TI - An evaluation of nurses' professional autonomy in Turkey. AB - BACKGROUND: The development of a profession's autonomy closely relates to that profession's level of autonomy in performing its specific role. For the nursing profession, this key role is nursing care. OBJECTIVES: This study was undertaken to evaluate the professional autonomy of nurses in care provision, from an ethical perspective. RESEARCH DESIGN: A mixed methods approach is employed in this research, which makes use of both quantitative and qualitative methods. The quantitative dimension of this research covers sociodemographic aspects and makes use of the Sociotropy-Autonomy Scale. The qualitative dimension of the research relates to the factors that affect professional autonomy in nursing care. PARTICIPANTS AND RESEARCH CONTEXT: The sample consisted of 30 nurses working in the orthopedics, neurology, or intensive care units of three hospitals. ETHICAL CONSIDERATIONS: Before conducting this research, we received permission from the ethical committee, as well as written permits from all the institutions in which the research was carried out. Informed consent was obtained from all participants. FINDINGS: According to the findings of this study, only 6.7% of the nurses surveyed stated that nurses had professional autonomy; they also stated that professional autonomy in nursing was mostly restricted by the need to be "dependent upon the physician in nursing implementations" and that autonomy in nursing care was mostly limited by a "high number of patients per nurse." DISCUSSION: This study determined that delays in resolving problems with regard to professional autonomy in nursing care in Turkey could be creating many of the professional and ethical problems that nurses face there. CONCLUSION: It is recommended that: individuals choose the nursing profession conscientiously; nurses need to be given professional awareness; their professional organizations need to be strengthened; and plans need to be made to increase research and to accumulate both knowledge and expertise. PMID- 24225056 TI - Effects of carvedilol treatment on cardiac cAMP response element binding protein expression and phosphorylation in acute coxsackievirus B3-induced myocarditis. AB - BACKGROUND: The role of beta-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of beta adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective beta-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis. METHODS: This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied. RESULTS: The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-alpha in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-alpha were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-alpha with amelioration of acute viral myocarditis. CONCLUSION: These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation. PMID- 24225058 TI - Evaluating moral reasoning in nursing education. AB - Evidence-based practice suggests the best approach to improving professionalism in practice is ethics curricula. However, recent research has demonstrated that millennium graduates do not advocate for patients or assert themselves during moral conflicts. The aim of this article is the exploration of evaluation techniques to evaluate one measurable outcome of ethics curricula: moral reasoning. A review of literature, published between 1995 and 2013, demonstrated that the moral orientations of care and justice as conceptualized by Gilligan and Kohlberg are utilized by nursing students to solve ethical dilemmas. Data obtained by means of reflective journaling, Ethics of Care Interview (ECI) and Defining Issues Test (DIT), would objectively measure the interrelated pathways of care-based and justice-based moral reasoning. In conclusion, educators have an ethical responsibility to foster students' ability to exercise sound clinical judgment, and support their professional development. It is recommended that educators design authentic assessments to demonstrate student's improvement of moral reasoning. PMID- 24225059 TI - Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis. AB - OBJECTIVE: This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. METHODS: Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. RESULTS: Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 um in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including alpha-tubulin and beta-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L lysine and L-arginine between chondrocytes. CONCLUSIONS: This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID- 24225060 TI - Incarcerated hernia in a trocar site following laparoscopic gastric bypass. AB - This paper reports a case of small bowel occlusion due to the herniation of an ileal ansa at the site of the insertion of a 12-mm trocar. A 28-year-old obese female patient underwent laparoscopic surgery for gastric bypass, the skin incisions of the trocar insertion sites were closed with absorbable sutures. Small bowel occlusion occurred on post-operative day 6 and the patient again underwent laparoscopic surgery. Laparoscopic exploration confirmed the suspected presence of the incarcerated hernia of an ileal ansa at the site of the trocar insertion which was freed without any need for bowel resection. The fascial defect was successfully closed under direct vision with the use of a special system of fascial sutures. PMID- 24225061 TI - Socioeconomic and disability consequences of injuries in the Sudan: a community based survey in Khartoum State. AB - BACKGROUND: Fatal and non-fatal injuries are of increasing public health concern globally, particularly in low and middle-income countries. Injuries sustained by individuals also impact society, creating a loss of productivity with serious economic consequences. In Sudan, there is no documentation of the burden of injuries on individuals and society. METHODS: A community-based survey was performed in Khartoum State, using a stratified two-stage cluster sampling technique. Households were selected in each cluster by systematic random sampling. Face-to-face interviews during October and November 2010 were conducted. Fatal injuries occurring during 5 years preceding the survey and non fatal injuries occurring during 12 months preceding interviews were included. RESULTS: The total number of individuals included was 5661, residing in 973 households. There were 28 deaths due to injuries out of a total of 129 reported deaths over 5 years. A total of 441 cases of non-fatal injuries occurred during the 12 months preceding the survey. The number of disability days differed significantly between mechanisms of injury. Road traffic crashes and falls caused the longest duration of disability. Men had a higher probability than women of losing a job due to an injury. CONCLUSIONS: This study demonstrates the importance of prioritising prevention of road traffic crashes and falls. The loss of productivity in lower socioeconomic strata highlights the need for social security policies. Further research is needed for estimating the economic cost of injuries in Sudan. PMID- 24225063 TI - Acute exercise and postprandial lipemia in young people. AB - Exaggerated postprandial triacylglycerol concentrations (TAG) independently predict future cardiovascular events. Acute exercise and diet interventions attenuate postprandial TAG in adults. This paper aims to examine the exercise postprandial lipemia studies published to date in young people. Nine studies satisfied the inclusion criteria adopted for this summary. The majority of studies are in boys (22% girls) and have shown a single ~60-min session of moderate-intensity exercise, performed 12-18 hours before a standardized meal, reduces postprandial TAG. Manipulations of exercise duration and intensity suggest an exercise energy expenditure dose-dependent response is not supported directly in healthy young people. Studies investigating alternative exercise bouts have reported lower postprandial TAG after simulated intermittent games activity, high-intensity interval running and cumulative 10-min blocks over several hours, which may appeal to the spontaneous physical activity habits of young people. Although extension of these initial findings is warranted, exercise may be an effective strategy to promote regular benefits in TAG metabolism in children and adolescents; this may contribute to an improved cardiovascular disease risk profile early in life. PMID- 24225062 TI - CoMAGC: a corpus with multi-faceted annotations of gene-cancer relations. AB - BACKGROUND: In order to access the large amount of information in biomedical literature about genes implicated in various cancers both efficiently and accurately, the aid of text mining (TM) systems is invaluable. Current TM systems do target either gene-cancer relations or biological processes involving genes and cancers, but the former type produces information not comprehensive enough to explain how a gene affects a cancer, and the latter does not provide a concise summary of gene-cancer relations. RESULTS: In this paper, we present a corpus for the development of TM systems that are specifically targeting gene-cancer relations but are still able to capture complex information in biomedical sentences. We describe CoMAGC, a corpus with multi-faceted annotations of gene cancer relations. In CoMAGC, a piece of annotation is composed of four semantically orthogonal concepts that together express 1) how a gene changes, 2) how a cancer changes and 3) the causality between the gene and the cancer. The multi-faceted annotations are shown to have high inter-annotator agreement. In addition, we show that the annotations in CoMAGC allow us to infer the prospective roles of genes in cancers and to classify the genes into three classes according to the inferred roles. We encode the mapping between multi faceted annotations and gene classes into 10 inference rules. The inference rules produce results with high accuracy as measured against human annotations. CoMAGC consists of 821 sentences on prostate, breast and ovarian cancers. Currently, we deal with changes in gene expression levels among other types of gene changes. The corpus is available at http://biopathway.org/CoMAGCunder the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0). CONCLUSIONS: The corpus will be an important resource for the development of advanced TM systems on gene-cancer relations. PMID- 24225064 TI - The impact of resilience on psychological outcomes in women after preeclampsia: an observational cohort study. AB - BACKGROUND: Preeclampsia is a frequent obstetric complication which affects the mother's and the fetus's health and can be life threatening. It also has an impact on psychological outcomes. There may be protective variables such as resilience shielding against psychosocial distress in women experiencing these pregnancy complications. The aim of this study was to examine differences in resilience in terms of quality of life, depression and post-traumatic stress symptoms in women after preeclampsia. METHODS: Four international validated questionnaires were used to measure the psychological outcomes (Medical Outcome Study Short-Form SF12, Edinburgh Postnatal Depression Scale EPDS, Resilience Scale RS13, Impact of Event Scale IES-R). Statistical analyses were performed using independent-samples t-test and chi-square test. RESULTS: 67 women with previous preeclampsia returned the questionnaires. Women with high resilience showed significantly less depression (p = 0.001) and better mental quality of life (p = 0.002) compared to women with low resilience. No group differences were found on the medical and socio-demographic characteristics. CONCLUSIONS: Resilience has an important impact on the psychological outcomes in women after preeclampsia. A screening for resilience, depression and quality of life may be appropriate to identify these women. PMID- 24225065 TI - A surveillance system to assess the need for updating systematic reviews. AB - BACKGROUND: Systematic reviews (SRs) can become outdated as new evidence emerges over time. Organizations that produce SRs need a surveillance method to determine when reviews are likely to require updating. This report describes the development and initial results of a surveillance system to assess SRs produced by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program. METHODS: Twenty-four SRs were assessed using existing methods that incorporate limited literature searches, expert opinion, and quantitative methods for the presence of signals triggering the need for updating. The system was designed to begin surveillance six months after the release of the original review, and then ceforth every six months for any review not classified as being a high priority for updating. The outcome of each round of surveillance was a classification of the SR as being low, medium or high priority for updating. RESULTS: Twenty-four SRs underwent surveillance at least once, and ten underwent surveillance a second time during the 18 months of the program. Two SRs were classified as high, five as medium, and 17 as low priority for updating. The time lapse between the searches conducted for the original reports and the updated searches (search time lapse - STL) ranged from 11 months to 62 months: The STL for the high priority reports were 29 months and 54 months; those for medium priority reports ranged from 19 to 62 months; and those for low priority reports ranged from 11 to 33 months. Neither the STL nor the number of new relevant articles was perfectly associated with a signal for updating. Challenges of implementing the surveillance system included determining what constituted the actual conclusions of an SR that required assessing; and sometimes poor response rates of experts. CONCLUSION: In this system of regular surveillance of 24 systematic reviews on a variety of clinical interventions produced by a leading organization, about 70% of reviews were determined to have a low priority for updating. Evidence suggests that the time period for surveillance is yearly rather than the six months used in this project. PMID- 24225066 TI - Assessing the 'system' in safe systems-based road designs: using cognitive work analysis to evaluate intersection designs. AB - While a safe systems approach has long been acknowledged as the underlying philosophy of contemporary road safety strategies, systemic applications are sparse. This article argues that systems-based methods from the discipline of Ergonomics have a key role to play in road transport design and evaluation. To demonstrate, the Cognitive Work Analysis framework was used to evaluate two road designs - a traditional Melbourne intersection and a cut-through design for future intersections based on road safety safe systems principles. The results demonstrate that, although the cut-through intersection appears different in layout from the traditional intersection, system constraints are not markedly different. Furthermore, the analyses demonstrated that redistribution of constraints in the cut-through intersection resulted in emergent behaviour, which was not anticipated and could prove problematic. Further, based on the lack of understanding of emergent behaviour, similar design induced problems are apparent across both intersections. Specifically, incompatibilities between infrastructure, vehicles and different road users were not dealt with by the proposed design changes. The importance of applying systems methods in the design and evaluation of road transport systems is discussed. PMID- 24225067 TI - Prevalence and treatment gap in childhood epilepsy in a north Indian city: a community-based study. AB - BACKGROUND: Epilepsy is one of the most common neurological disorders prevalent in childhood period. There is scarcity of epidemiological data, required to plan services in resource constrained developing nations. OBJECTIVE: To study the prevalence and treatment gap in childhood epilepsy in north Indian city, in the age group of 1-18 years. METHODS: A two stage stratified cluster sampling; probability proportionate to size (PPS) was employed. A ten question screening questionnaire was employed to identify the presence of epilepsy. Definitions provided by International League against Epilepsy (ILAE) were used to classify screen positive subjects as epilepsy and to calculate the treatment gap. RESULTS: The prevalence rate for epilepsy was 6.24/1000 population. Febrile seizures and neurocysticercosis were most common causes of symptomatic seizures in childhood. CONCLUSION: This study of epidemiology of epilepsy provides valuable aid in optimizing effective community approach, thereby improving outcomes of childhood epilepsy. PMID- 24225068 TI - Characterization of the impact of catheter-tissue contact force in lesion formation during cavo-tricuspid isthmus ablation in an experimental swine model. AB - AIMS: Catheter-tissue contact is critical for effective lesion creation. The objective of this study was to determine in an experimental swine model the pathological effects of cavo-tricuspid isthmus ablation using two systems that provide reliable measures of the pressure at the catheter tip during radiofrequency ablation procedures. METHODS AND RESULTS: We performed the procedure in eight pigs in our experimental electrophysiology laboratory after right femoral vein dissection and insertion of a 12 Fr. introducer during general anaesthesia and endotracheal intubation. The target contact force during the applications was <10 grs. (axial or lateral), 10-20, 20-30, and >30 grs. in two pigs each. The power was set at 40 W and maximum target temperature at 45 degrees C. We performed a radiofrequency line dragging from the tricuspid valve to the inferior vena cava in the eight pigs. Euthanasia of the animals was carried out a week after the procedure and a pathological examination of the lesions was performed. In the endocardial macroscopic analysis the extent of lesions, presence of thrombus, transmurality, and endothelial rupture was assessed. External surface was examined searching for transmural lesions. The mean contact force applied was 18.7 +/- 8.4 grs. and the mean depth of the lesions was 3.6 +/- 2 mm. Lesions were never transmural with average forces <10 grs., and the mean depth was very low (0.75 mm). To achieve transmural lesions contact forces of at least 20 grs. were required. We found a positive correlation (r = 0.85, P < 0.05) between the average force during the applications and depth of the lesions. CONCLUSION: When ablating the cavo-tricuspid isthmus in a swine model, contact forces of at least 20 grs. are required to achieve transmural lesions. Catheter tissue contact is critical for effective lesion creation. This information is important for improving ablation efficacy. PMID- 24225069 TI - A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan. AB - BACKGROUND: The publication of protocols by medical journals is increasingly becoming an accepted means for promoting good quality research and maximising transparency. Recently, Finfer and Bellomo have suggested the publication of statistical analysis plans (SAPs).The aim of this paper is to make public and to report in detail the planned analyses that were approved by the Trial Steering Committee in May 2010 for the principal papers of the PACE (Pacing, graded Activity, and Cognitive behaviour therapy: a randomised Evaluation) trial, a treatment trial for chronic fatigue syndrome. It illustrates planned analyses of a complex intervention trial that allows for the impact of clustering by care providers, where multiple care-providers are present for each patient in some but not all arms of the trial. RESULTS: The trial design, objectives and data collection are reported. Considerations relating to blinding, samples, adherence to the protocol, stratification, centre and other clustering effects, missing data, multiplicity and compliance are described. Descriptive, interim and final analyses of the primary and secondary outcomes are then outlined. CONCLUSIONS: This SAP maximises transparency, providing a record of all planned analyses, and it may be a resource for those who are developing SAPs, acting as an illustrative example for teaching and methodological research. It is not the sum of the statistical analysis sections of the principal papers, being completed well before individual papers were drafted. TRIAL REGISTRATION: ISRCTN54285094 assigned 22 May 2003; First participant was randomised on 18 March 2005. PMID- 24225070 TI - Identification of the gene for beta-fructofuranosidase from Ceratocystis moniliformis CMW 10134 and characterization of the enzyme expressed in Saccharomyces cerevisiae. AB - BACKGROUND: beta-Fructofuranosidases (or invertases) catalyse the commercially important biotransformation of sucrose into short-chain fructooligosaccharides with wide-scale application as a prebiotic in the functional foods and pharmaceutical industries. RESULTS: We identified a beta-fructofuranosidase gene (CmINV) from a Ceratocystis moniliformis genome sequence using protein homology and phylogenetic analysis. The predicted 615 amino acid protein, CmINV, grouped with an existing clade within the glycoside hydrolase (GH) family 32 and showed typical conserved motifs of this enzyme family. Heterologous expression of the CmINV gene in Saccharomyces cerevisiae BY4742?suc2 provided further evidence that CmINV indeed functions as a beta-fructofuranosidase. Firstly, expression of the CmINV gene complemented the inability of the ?suc2 deletion mutant strain of S. cerevisiae to grow on sucrose as sole carbohydrate source. Secondly, the recombinant protein was capable of producing short-chain fructooligosaccharides (scFOS) when incubated in the presence of 10% sucrose. Purified deglycosylated CmINV protein showed a molecular weight of ca. 66 kDa and a Km and Vmax on sucrose of 7.50 mM and 986 MUmol/min/mg protein, respectively. Its optimal pH and temperature conditions were determined to be 6.0 and 62.5 degrees C, respectively. The addition of 50 mM LiCl led to a 186% increase in CmINV activity. Another striking feature was the relatively high volumetric production of this protein in S. cerevisiae as one mL of supernatant was calculated to contain 197 +/- 6 International Units of enzyme. CONCLUSION: The properties of the CmINV enzyme make it an attractive alternative to other invertases being used in industry. PMID- 24225071 TI - Visceral leishmaniasis with cutaneous dissemination in a renal transplant recipient. PMID- 24225072 TI - The red cell distribution width (RDW): value and role in preterm, IUGR (intrauterine growth restricted), full-term infants. AB - OBJECTIVE: To measure the red cell distribution width (RDW) ranges at birth and to evaluate potential association with typical neonatal diseases: patent of the ductus arteriousus (PDA), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS) mortality. METHODS: Forty-six full-term, 41 preterm, and 35 intrauterine growth restricted (IUGR) infants participated in this retrospective, observational study. RDW was measured before 3 days of life (T0) in all infants, and at first month of life (T1) in preterm/IURG patients. RESULTS: RDW% mean (standard deviation) at T0 was: 15.65 (1.18) in full-term newborns; 17.7 (2.06) in preterm; 17.45 (1.81) in IUGR. A negative correlation (r = -0.51; P < 0.001) between RDW and gestational age was found. RDW at T1 was: 17.25 (2.19) in the preterm group; 17.37 (2.56) in IUGR group. Fourteen preterm infants reported: 12 PDA, 5 LOS, 4 BPD, and 3 died; 10 IUGR infants had: 4 PDA, 6 LOS, 3 BPD, and 1 died. RDW of IUGR infants suffering from those pathologies was not statistically different compared with unaffected infants, while preterm newborns with pathologies reported higher RDW: PDA vs. PDA absent: P = 0.008 at T0; P < 0.002 at T1. BPD vs. BPD absent: P < 0.005 at T1. LOS vs. LOS absent: P < 0.005 at T0. RDW in preterm/IUGR population was associated with early mortality, T0: dead 21.2 (2.7) vs. alive 16.7 (1.7), P < 0.0001. CONCLUSION: RDW and gestational age at birth were negatively correlated. High RDW resulted to be an indication of risk for critical newborns. This parameter can be inexpensively and routinely verified and further studies are required to confirm its prognostic role in neonatal pathologies. PMID- 24225073 TI - Post-stress left ventricular ejection fraction drop in patients with diabetes: a gated myocardial perfusion imaging study. AB - BACKGROUND: To evaluate the relevance of stress-induced decrease in left ventricular ejection fraction (LVEF) in patients with type-2 diabetes. METHODS: A total of 684 diabetic patients with available rest and post-stress gated myocardial perfusion single-photon emission computed tomography (MPS) data were enrolled. An automated algorithm was used to determine the perfusion scores using a 17-segment model. LVEF drop was considered significant if the post-stress LVEF was >=5% below the rest value. Follow-up data were available in 587 patients that were followed for the occurrence of cardiac death, nonfatal myocardial infarction, or unstable angina requiring revascularization. RESULTS: A post stress LVEF drop >=5% was observed in 167 (24%) patients. Patients with LVEF drop had higher summed stress score (p < 0.05), summed difference score (p < 0.001), and rest LVEF (p < 0.001) compared to patients without. Conversely, summed rest score, a measure of infarct size, was comparable between the two groups. At multivariable analysis, summed difference score and rest LVEF were independent predictors (both p < 0.001) of post-stress LVEF drop. Myocardial perfusion was abnormal in 106 (63%) patients with post-stress LVEF drop and in 296 (57%) of those without (p = 0.16). The overall event-free survival was lower in patients with post-stress LVEF drop than in those without (log rank chi2 7.7, p < 0.005). After adjusting for clinical data and MPS variables, the hazard ratio for cardiac events for post-stress LVEF drop was 1.52 (p < 0.01). CONCLUSIONS: In diabetic patients stress-induced ischemia is an independent predictor of post-stress LVEF drop; however, a reduction in LVEF is detectable also in patients with normal perfusion. Finally, post-stress LVEF drop increases the risk of subsequent cardiac events in diabetic patients. PMID- 24225074 TI - Creating a gold medal Olympic and Paralympics health care team: a satisfaction survey of the mobile medical unit/polyclinic team training for the Vancouver 2010 winter games. AB - BACKGROUND: The mobile medical unit/polyclinic (MMU/PC) was an essential part of the medical services to support ill or injured Olympic or Paralympics family during the 2010 Olympic and Paralympics winter games. The objective of this study was to survey the satisfaction of the clinical staff that completed the training programs prior to deployment to the MMU. METHODS: Medical personnel who participated in at least one of the four training programs, including (1) week end sessions; (2) web-based modules; (3) just-in-time training; and (4) daily simulation exercises were invited to participate in a web-based survey and comment on their level of satisfaction with training program. RESULTS: A total of 64 (out of 94 who were invited) physicians, nurses and respiratory therapists completed the survey. All participants reported favorably that the MMU/PC training positively impacted their knowledge, skills and team functions while deployed at the MMU/PC during the 2010 Olympic Games. However, components of the training program were valued differently depending on clinical job title, years of experience, and prior experience in large scale events. Respondents with little or no experience working in large scale events (45%) rated daily simulations as the most valuable component of the training program for strengthening competencies and knowledge in clinical skills for working in large scale events. CONCLUSION: The multi-phase MMU/PC training was found to be beneficial for preparing the medical team for the 2010 Winter Games. In particular this survey demonstrates the effectiveness of simulation training programs on teamwork competencies in ad hoc groups. PMID- 24225075 TI - Are anti-proteinase-3 ANCA a useful marker of granulomatosis with polyangiitis (Wegener's) relapses? Results of a retrospective study on 126 patients. AB - OBJECTIVES: Predicting granulomatosis with polyangiitis (Wegener's) (GPA) relapses based on ANCA titers remains a source of debate. Our objective was to evaluate the relevance of monitoring PR3-ANCA titers for GPA management. METHODS: This retrospective study included 126 patients fulfilling the 1990 ACR criteria for GPA and PR3-ANCA-positive at the time of diagnosis. Disease activity was assessed with BVAS/WG and Disease Extent Index. For each patient, a median of 12 serum samples was analyzed, i.e., one every 5.5months. RESULTS: Induction therapy obtained remission in 88% of the patients. ANCA became negative by IF for 70/115 (60.9%) patients and by ELISA for 90/115 (78.3%). After median follow-up of 70months, 85/126 (67.5%) patients had 154 clinical relapses associated with cANCA and PR3-ANCA-positivity for 122 (79.2%) and 102 (66.2%) of them, respectively. Relapse-free survival was significantly longer for patients who remained PR3-ANCA negative (HR 0.60 [95% CI 0.39-0.92], P=0.02). Individual ANCA-profile analysis revealed that, for 60% of GPA patients, clinical outcomes and ANCA-titer changes were closely associated, i.e., ANCA were always positive during relapses and negative during remission. The 35 patients with fluctuating ANCA-positivity during remission were in partial remission or had developed grumbling GPA. CONCLUSION: Although ANCA were positive during most systemic relapses or residual disease, no strict clinical-immunological correspondence was observed for 25% of the patients. Thus, GPA management cannot be based on ANCA levels alone. PMID- 24225076 TI - Molecular and cellular mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system. AB - Over the last decade multiple autoantigens located on the plasma membrane of neurons have been identified. Neuronal surface antigens include molecules directly involved in neurotransmission and excitability. Binding of the antibody to the antigen may directly alter the target protein's function, resulting in neurological disorders. The often striking reversibility of symptoms following early aggressive immunotherapy supports a pathogenic role for autoantibodies to neuronal surface antigens. In order to better understand and treat these neurologic disorders it is important to gain insight in the underlying mechanisms of antibody pathogenicity. In this review we discuss the clinical, circumstantial, in vitro and in vivo evidence for neuronal surface antibody pathogenicity and the possible underlying cellular and molecular mechanisms. This review shows that antibodies to neuronal surface antigens are often directed at conformational epitopes located in the extracellular domain of the antigen. The conformation of the epitope can be affected by specific posttranslational modifications. This may explain the distinct clinical phenotypes that are seen in patients with antibodies to antigens that are expressed throughout the brain. Furthermore, it is likely that there is a heterogeneous antibody population, consisting of different IgG subtypes and directed at multiple epitopes located in an immunogenic region. Binding of these antibodies may result in different pathophysiological mechanisms occurring in the same patient, together contributing to the clinical syndrome. Unraveling the predominant mechanism in each distinct antigen could provide clues for therapeutic interventions. PMID- 24225077 TI - Psychometric properties of a short version of the HIV stigma scale, adapted for children with HIV infection. AB - BACKGROUND: HIV is a stigmatizing medical condition. The concept of HIV stigma is multifaceted, with personalized stigma (perceived stigmatizing consequences of others knowing of their HIV status), disclosure concerns, negative self-image, and concerns with public attitudes described as core aspects of stigma for individuals with HIV infection. There is limited research on HIV stigma in children. The aim of this study was to test a short version of the 40-item HIV Stigma Scale (HSS-40), adapted for 8-18 years old children with HIV infection living in Sweden. METHODS: A Swedish version of the HSS-40 was adapted for children by an expert panel and evaluated by think aloud interviews. A preliminary short version with twelve items covering the four dimensions of stigma in the HSS-40 was tested. The psychometric evaluation included inspection of missing values, principal component analysis (PCA), internal consistency, and correlations with measures of health-related quality of life (HRQoL). RESULTS: Fifty-eight children, representing 71% of all children with HIV infection in Sweden meeting the inclusion criteria, completed the 12-item questionnaire. Four items concerning participants' experiences of others' reactions to their HIV had unacceptable rates of missing values and were therefore excluded. The remaining items constituted an 8-item scale, the HIV Stigma Scale for Children (HSSC-8), measuring HIV-related disclosure concerns, negative self-image, and concerns with public attitudes. Evidence for internal validity was supported by a PCA, suggesting a three factor solution with all items loading on the same subscales as in the original HSS-40. The scale demonstrated acceptable internal consistency, with exception for the disclosure concerns subscale. Evidence for external validity was supported in correlational analyses with measures of HRQoL, where higher levels of stigma correlated with poorer HRQoL. CONCLUSION: The results suggest feasibility, reliability, as well as internal and external validity of the HSSC-8, an HIV stigma scale for children with HIV infection, measuring disclosure concerns, negative self-image, and concerns with public attitudes. The present study shows that different aspects of HIV stigma can be assessed among children with HIV in the age group 8-18. PMID- 24225078 TI - Immune activation, HIV persistence, and the cure. AB - HIV infection is characterized by persistent immune activation, even in the context of suppressive antiretroviral therapy. This persistent activation, which appears to be fueled by microbial translocation from the gut resulting from HIV related damage, is associated with deficits in immune function that in turn contribute to persistent activation. The presence of latent HIV reservoirs in lymphoid tissues also provokes immune activation in the context of immune suppression, resulting in expansion of the viral reservoir and potential viral replication, even with suppressive antiretroviral therapy. Therapeutic strategies are being devised to reduce persistent immune activation and limit the size of the HIV reservoir. This article summarizes a presentation by Daniel C. Douek, MD, PhD, at the IAS-USA continuing education program held in San Francisco, California, in March 2013. PMID- 24225079 TI - Linkage, engagement, and retention in HIV care among vulnerable populations: "I"m sick and tired of being sick and tired". AB - There are disparities in engagement and retention in HIV care and outcomes of care across segments of society. For example, HIV mortality rates remain markedly elevated among black women and men compared with their white counterparts. These differences reflect broader disparities across social, economic, and cultural lines. Improvement in engagement and retention in HIV care requires interventions that account for forces present in the socioecologic framework of health behaviors. Improvement in linkage to care at HIV testing is crucial to overall engagement and retention in care. Strategies for linkage to care at testing can help overcome many of the forces that result in failure to engage and remain in care by starting the patient on a solid path to clinical care. This article summarizes a presentation by Victoria A. Cargill, MD, MSCE, at the IAS-USA continuing education program held in New York, New York, in May 2013. PMID- 24225080 TI - Implications of the Affordable Care Act for people with HIV infection and the Ryan White HIV/AIDS Program: what does the future hold? AB - There are numerous aspects of the Patient Protection and Affordable Care Act that will be important for people in the United States with HIV infection, including consumer protections and private insurance reforms, establishment of health care marketplaces in every state, new benefit standards, Medicare fixes, prevention enhancements, expansion of Medicaid, and health system improvements. However, it is unlikely that these changes will address all the needs of people with HIV infection in the United States. The Ryan White HIV/AIDS Program will thus remain crucial for the provision of adequate health care to HIV-infected individuals, but it will need to change. Changes in the role of the Ryan White HIV/AIDS Program will depend largely on state decisions on Medicaid expansion and health care marketplaces. This article summarizes a presentation by Jennifer Kates, PhD, at the IAS-USA continuing education program held in New York, New York, in April 2013. PMID- 24225081 TI - Porvoo sarcopenia and nutrition trial: effects of protein supplementation on functional performance in home-dwelling sarcopenic older people - study protocol for a randomized controlled trial. AB - BACKGROUND: Age-related muscle loss (that is, sarcopenia) is a common health problem among older people. Physical exercise and dietary protein have been emphasized in prevention and treatment of sarcopenia. Rigorous trials investigating the effects of protein supplementation on physical performance in sarcopenic populations are still scarce. The aim of this study is to investigate the effects of protein supplementation along with simple home-based exercises on physical performance among home-dwelling sarcopenic older people. METHODS/DESIGN: During 2012 the entire 75 and older population (N = 3,275) living in Porvoo, Finland was contacted via a postal questionnaire. Persons at risk of sarcopenia are screened with hand grip strength and gait speed. Poorly performing persons are further examined by segmental bioimpendance spectroscopy to determine their skeletal muscle index. Sarcopenic patients (target N = 250) will be enrolled in a 12-month randomized controlled trial with three arms: 1) no supplementation, 2) protein supplementation (20 grams twice a day), and 3) isocaloric placebo. All the participants will receive instructions on simple home-based exercises, dietary protein, and vitamin D supplementation (20 MUg/d). The recruitment of patients will be completed during 2013. The primary endpoint of the trial is the change in short physical performance battery score and percentage of patients maintaining or improving their physical performance. Secondary endpoints will be, among other things, changes in muscle functions, nutritional status, body composition, cognition, quality of life, use of health care services, falls, and mortality. The assessment times will be 0, 6, 12 and 24 months. DISCUSSION: To our knowledge, this is the first large scale randomized controlled trial among community dwelling older people with sarcopenia that focuses on the effects of protein supplementation on physical performance. TRIAL REGISTRATION: ACTRN12612001253897, date of registration 28 October 2012, first patient was randomized 11 April 2012. PMID- 24225083 TI - Ten recommendations for creating usable bioinformatics command line software. AB - Bioinformatics software varies greatly in quality. In terms of usability, the command line interface is the first experience a user will have of a tool. Unfortunately, this is often also the last time a tool will be used. Here I present ten recommendations for command line software author's tools to follow, which I believe would greatly improve the uptake and usability of their products, waste less user's time, and improve the quality of scientific analyses. PMID- 24225082 TI - ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians. AB - BACKGROUND: Many long non-coding RNA (lncRNA) genes identified in mammals have multiple exons and functional domains, allowing them to bind to polycomb proteins, DNA methyltransferases, and specific DNA sequences to regulate genome methylation. Little is known about the origin and evolution of lncRNAs. ANRIL/CDKN2B-AS consists of 19 exons on human chromosome 9p21 and regulates the expression of three cyclin-dependent kinase inhibitors (CDKN2A/ARF/CDKN2B). RESULTS: ANRIL/CDKN2B-AS originated in placental mammals, obtained additional exons during mammalian evolution but gradually lost them during rodent evolution, and reached 19 exons only in simians. ANRIL lacks splicing signals in mammals. In simians, multiple transposons were inserted and transformed into exons of the ANRIL gene, after which ANRIL became highly conserved. A further survey reveals that multiple transposons exist in many lncRNAs. CONCLUSIONS: ANRIL shows a two stage, clade-specific evolutionary process and is fully developed only in simians. The domestication of multiple transposons indicates an impressive pattern of "evolutionary tinkering" and is likely to be important for ANRIL's structure and function. The evolution of lncRNAs and that of transposons may be highly co-opted in primates. Many lncRNAs may be functional only in simians. PMID- 24225084 TI - The degradation of chondrogenic pellets using cocultures of synovial fibroblasts and U937 cells. AB - Osteoarthritis (OA) of the knee is often characterized by joint space narrowing on X-ray, knee pain, and a loss of joint function through progressive cartilage degradation and intermittent synovial inflammation. The objective of this work was to develop an in vitro model in a clinically relevant system. Normal human synovial fibroblasts were cultured with U937 cells for 3 days then combined with a chondrogenic stem cell pellet for another 4 days. This culture system mimicked many of the aspects of early stage OA including production of cytokines and degradative enzymes, MMP-1 and MMP-3, resulting in a conditioned medium profile similar to OA synovial fluid. This catabolic environment resulted in the release of glycosaminoglycan (GAG) from the pellet. In a similar manner to early stage OA, the pellet had increased aggrecan and collagen II expression. All of these effects are hallmarks of early stage OA. This relatively simple tissue model containing a 3D cartilage component interacting with synoviocytes and macrophages could be useful to understand early causes and progression of OA. It can be scaled easily thus useful for high throughput screening of disease modifying drugs in a clinically relevant system. PMID- 24225085 TI - A neural stem/precursor cell monolayer for neural tissue engineering. AB - The purpose of this study was to prepare a monolayer of neural stem/precursor cells (NSPCs) for neural tissue engineering applications. Two components present in serum, fibronectin and epidermal growth factor (EGF) were added into DMEM/F12 medium (termed medium B) to examine the effect of the migration-, proliferation- and differentiation-promoting potential on the cultured NSPCs, isolated from embryonic rat cerebral cortex. Compared with the serum effect, medium B also permitted neurosphere attachment onto the substrate surface and cell migration out of neurospheres extensively, but enhanced more extensive cell division and slowed down NSPC differentiation to generate a confluent NSPC monolayer. It was found the medium B-treated NSPCs possessed the capability to form typical neurospheres or to undergo differentiation into neuron-related cell types on various biomaterial surfaces. Therefore, we proposed a two-stage process for wound healing or nerve conduit preparation. Extensive NSPC division and MAP2 positive neuron differentiation were manipulated in NSPCs cultured in the medium B followed by the neuronal differentiation-favorable medium. These results should be useful for controlling the proliferation and differentiation of NSPCs on various biomaterials and conduits in neuroscience research. PMID- 24225086 TI - Xin is a marker of skeletal muscle damage severity in myopathies. AB - Xin is a striated muscle-specific protein that is localized to the myotendinous junction in skeletal muscle. However, in injured mouse muscle, Xin expression is up-regulated and observed throughout skeletal muscle fibers and within satellite cells. In this study, Xin was analyzed by immunofluorescent staining in skeletal muscle samples from 47 subjects with various forms of myopathy, including muscular dystrophies, inflammatory myopathies, mitochondrial/metabolic myopathy, and endocrine myopathy. Results indicate that Xin immunoreactivity is positively and significantly correlated (rs = 0.6175, P = <0.0001) with the severity of muscle damage, regardless of myopathy type. Other muscle damage measures also showed a correlation with severity [Xin actin-binding repeat-containing 2 (rs = 0.7108, P = 0.0006) and collagen (rs = 0.4683, P = 0.0783)]. However, because only Xin lacked immunoreactivity within the healthy muscle belly, any detectable immunoreactivity for Xin was indicative of muscle damage. We also investigated the expression of Xin within the skeletal muscle of healthy individuals subjected to damaging eccentric exercise. Consistent with our previously mentioned results, Xin immunoreactivity was increased 24 hours after exercise in damaged muscle fibers and within the activated muscle satellite cells. Taken together, these data demonstrate Xin as a useful biomarker of muscle damage in healthy individuals and in patients with myopathy. The strong correlation between the degree of muscle damage and Xin immunoreactivity suggests that Xin may be a suitable outcome measure to evaluate disease progression and treatment effects in clinical trials. PMID- 24225088 TI - Implementation of CFD modeling in the performance assessment and optimization of secondary clarifiers: the PVSC case study. AB - The water industry and especially the wastewater treatment sector has come under steadily increasing pressure to optimize their existing and new facilities to meet their discharge limits and reduce overall cost. Gravity separation of solids, producing clarified overflow and thickened solids underflow has long been one of the principal separation processes used in treating secondary effluent. Final settling tanks (FSTs) are a central link in the treatment process and often times act as the limiting step to the maximum solids handling capacity when high throughput requirements need to be met. The Passaic Valley Sewerage Commission (PVSC) is interested in using a computational fluid dynamics (CFD) modeling approach to explore any further FST retrofit alternatives to sustain significantly higher plant influent flows, especially under wet weather conditions. In detail there is an interest in modifying and/or upgrading/optimizing the existing FSTs to handle flows in the range of 280-720 million gallons per day (MGD) (12.25-31.55 m(3)/s) in compliance with the plant's effluent discharge limits for total suspended solids (TSS). The CFD model development for this specific plant will be discussed, 2D and 3D simulation results will be presented and initial results of a sensitivity study between two FST effluent weir structure designs will be reviewed at a flow of 550 MGD (~24 m(3)/s) and 1,800 mg/L MLSS (mixed liquor suspended solids). The latter will provide useful information in determining whether the existing retrofit of one of the FSTs would enable compliance under wet weather conditions and warrants further consideration for implementing it in the remaining FSTs. PMID- 24225087 TI - Hepatitis C and alcohol exacerbate liver injury by suppression of FOXO3. AB - Hepatitis C virus (HCV) infection exacerbates alcoholic liver injury by mechanisms that include enhanced oxidative stress. The forkhead box transcription factor FOXO3 is an important component of the antioxidant stress response that can be altered by HCV. To test whether FOXO3 is protective for alcoholic liver injury, we fed alcohol to FOXO3(-/-) mice. After 3 weeks, one third of these mice developed severe hepatic steatosis, neutrophilic infiltration, and >10-fold alanine aminotransferase (ALT) elevations. In cell culture, either alcohol or HCV infection alone increased FOXO3 transcriptional activity and expression of target genes, but the combination of HCV and alcohol together caused loss of nuclear FOXO3 and decreased its transcriptional activity. This was accompanied by increased phosphorylation of FOXO3. Mice expressing HCV structural proteins on a background of reduced expression of superoxide dismutase 2 (SOD2; Sod2(+/-)) also had increased liver sensitivity to alcohol, with elevated ALT, steatosis, and lobular inflammation. Elevated ALT was associated with an alcohol-induced decrease in SOD2 and redistribution of FOXO3 to the cytosol. These results demonstrate that FOXO3 functions as a protective factor preventing alcoholic liver injury. The combination of HCV and alcohol, but not either condition alone, inactivates FOXO3, causing a decrease in expression of its target genes and an increase in liver injury. Modulation of the FOXO3 pathway is a potential therapeutic approach for HCV-alcohol-induced liver injury. PMID- 24225089 TI - Factors affecting the performance of a single-chamber microbial fuel cell-type biological oxygen demand sensor. AB - Microbial fuel cells (MFCs) are devices that exploit microorganisms as biocatalysts to degrade organic matter or sludge present in wastewater (WW), and thereby generate electricity. We developed a simple, low-cost single-chamber microbial fuel cell (SCMFC)-type biochemical oxygen demand (BOD) sensor using carbon felt (anode) and activated sludge, and demonstrated its feasibility in the construction of a real-time BOD measurement system. Further, the effects of anodic pH and organic concentration on SCMFC performance were examined, and the correlation between BOD concentration and its response time was analyzed. Our results demonstrated that the SCMFC exhibited a stable voltage after 132 min following the addition of synthetic WW (BOD concentration: 200 mg/L). Notably, the response signal increased with an increase in BOD concentration (range: 5-200 mg/L) and was found to be directly proportional to the substrate concentration. However, at higher BOD concentrations (>120 mg/L) the response signal remained unaltered. Furthermore, we optimized the SCMFC using synthetic WW, and tested it with real WW. Upon feeding real WW, the BOD values exhibited a standard deviation from 2.08 to 8.3% when compared to the standard BOD5 method, thus demonstrating the practical applicability of the developed system to real treatment effluents. PMID- 24225090 TI - Design, construction and performance of a horizontal subsurface flow wetland system in Australia. AB - Malabugilmah is a remote Aboriginal community located in Clarence Valley, Northern NSW, Australia. In 2006, seven horizontal subsurface flow wetland clusters consisting of 3 m * 2 m wetland cells in series were designed and constructed to treat septic tank effluent to a secondary level (Total Suspended Solids (TSS) < 30 mg/L and Biochemical Oxygen Demand (BOD5) <20 mg/L) and achieve >50% Total Nitrogen (TN) reduction, no net Total Phosphorus (TP) export and >=99.9% Faecal Coliform (FC) reduction. The wetland cell configuration allowed the wetlands to be located on steeper terrain, enabling effluent to be treated to a secondary level without the use of pumps. In addition to the water quality targets, the wetlands were designed and constructed to satisfy environmental, economic and social needs of the community. The wetland systems were planted with a local Australian wetland tree species which has become well established. Two wetland clusters have been monitored over the last 4 years. The wetlands have demonstrated to be robust over time, providing a high level of secondary treatment over an extended period. PMID- 24225091 TI - Biodegradation of Bisphenol-A in aerobic membrane bioreactor sludge. AB - Bisphenol-A (BPA) biodegradation was studied in a membrane bioreactor under aerobic conditions. The effects of the initial BPA concentration and initial chemical oxygen demand (COD) concentration on BPA biodegradation were investigated. The degradation process followed a first-order kinetic (more than 98% of BPA was removed) with a kinetic rate constant of 1.134 h(-1) using an initial BPA concentration of 1.0 mg L(-1). The kinetic rate constant decreased to 0.611 h(-1) when the initial BPA concentration increased to 5.0 mg L(-1). The initial COD concentration (400 and 2,000 mg L(-1)) did not affect the biodegradation kinetic of BPA. PMID- 24225092 TI - Performance of activated sludge diffusion for biological treatment of hydrogen sulphide gas emissions. AB - Odours from wastewater treatment plants are comprised of a mixture of various gases with hydrogen sulphide (H(2)S) often being the dominant constituent. Activated sludge diffusion (ASD) as a biotreatment system for odour abatement has been conducted for over 30 years but has limited broad application due to disagreement in the literature regarding the effect that ASD may have on wastewater treatment performance. The effects of continuous H(2)S diffusion at 25 ppmv, with weekly peaks of approximately 100 ppmv, on H(2)S removal efficiency and wastewater treatment performance was evaluated over a 2-month period using an activated sludge pilot plant. H(2)S removal averaged 100% during diffusion at 25 ppmv, and 98.9% during the 100 ppmv peak periods. A significant increase in mixed liquor volatile suspended solids concentration (P < 0.01) was observed during H(2)S diffusion, which may be due to an increase in H(2)S-degrading microorganisms. There was no adverse effect of H(2)S on nitrification throughout the ASD trials. Ammonia (NH(3)) removal was slightly better in the test receiving H(2)S diffusion (87.6%) than in the control (85.4%). H(2)S diffusion appeared to improve robustness of the AS biomass to operational upsets. PMID- 24225093 TI - Electrocoagulation for the removal of phenol and aldehyde contaminants from resin effluent. AB - This paper is a report on a study which aimed to investigate the effect of different current density, pH, temperature, and cathode-anode combination on the removal of phenol and aldehyde in two samples of actual resin effluent through the process of electrocoagulation using solar energy. Current density 60 A/m(2) and pH 6 proved to be the best levels for both contaminants. As for the effect of temperature, although the highest degree of phenol and aldehyde removal was achieved at 15 degrees C, 25 degrees C was taken to be the optimum temperature for economic reasons. The Fe-Fe combination of electrodes was found to be the best as it led to nearly 93% of phenol removal and approximately 95% of aldehyde removal. Also, the effect of electrode combination on energy consumption was studied. It was observed that the Fe-Fe combination consumed the least amount of energy (0.7-4.3 kWh/m(3) of wastewater in the case of phenol and 0.8-4 kWh/m(3) of wastewater in the case aldehyde). Moreover, the Fe-Fe combination brought about the best results in terms of chemical oxygen demand removal: 93% in both cases. Finally, an economic analysis was performed for the electrocoagulation process. PMID- 24225094 TI - Assessing the potential for restoration of surface permeability for permeable pavements through maintenance. AB - Permeable pavements (PPs) have been in use as stormwater management systems in Canada and the United States for over 20 years. After years of exposure to sediment and debris build-up, surface clogging reduces the infiltration of stormwater and inhibits the hydraulic and environmental functions of the pavement. Removal of surface material has been shown to restore infiltration but the majority of studies have been limited to small-scale testing. This paper presents the results of small- and full-sized equipment testing aimed at restoring surface permeability, including the first testing of regenerative-air and vacuum-sweeping streetsweepers in Ontario. Maintenance achieved partial restoration of PP surface permeability. Post-treatment surface infiltration rates displayed large spatial variability, highlighting that localized conditions throughout the pavement have a confounding influence on the overall effectiveness of maintenance. The impact of maintenance may be improved by establishing regular cleaning intervals and developing instructional guidelines for pavement owners and equipment operators. PMID- 24225095 TI - Metagenomes obtained by 'deep sequencing' - what do they tell about the enhanced biological phosphorus removal communities? AB - Metagenomics enables studies of the genomic potential of complex microbial communities by sequencing bulk genomic DNA directly from the environment. Knowledge of the genetic potential of a community can be used to formulate and test ecological hypotheses about stability and performance. In this study deep metagenomics and fluorescence in situ hybridization (FISH) were used to study a full-scale wastewater treatment plant with enhanced biological phosphorus removal (EBPR), and the results were compared to an existing EBPR metagenome. EBPR is a widely used process that relies on a complex community of microorganisms to function properly. Insight into community and species level stability and dynamics is valuable for knowledge-driven optimization of the EBPR process. The metagenomes of the EBPR communities were distinct compared to metagenomes of communities from a wide range of other environments, which could be attributed to selection pressures of the EBPR process. The metabolic potential of one of the key microorganisms in the EPBR process, Accumulibacter, was investigated in more detail in the two plants, revealing a potential importance of phage predation on the dynamics of Accumulibacter populations. The results demonstrate that metagenomics can be used as a powerful tool for system wide characterization of the EBPR community as well as for a deeper understanding of the function of specific community members. Furthermore, we discuss and illustrate some of the general pitfalls in metagenomics and stress the need of additional DNA extraction independent information in metagenome studies. PMID- 24225096 TI - Occurrence of earthy and musty odor compounds (geosmin, 2-methylisoborneol and 2,4,6-trichloroanisole) in biologically treated wastewater. AB - The concentrations of earthy and musty odor compounds (2-methylisoborneol (2 MIB), geosmin and 2,4,6-trichloroanisole (TCA)) in treated wastewater were measured. Concentrations of 2,4,6-TCA (4.3-37.7 ng/L) and geosmin (3.7-42.2 ng/L) higher than their odor thresholds were detected for effluents from large-scale treatment plants. The effluent from a small-scale wastewater plant treating toilet and kitchen wastewater contained the target earthy and musty odor compounds below the odor thresholds. The ozonation applied as an advanced wastewater treatment process was considerably more effective for the removal of 2,4,6-TCA than for the removal of 2-MIB and geosmin. The measured concentrations of 2,4,6-TCA in river environments without the influence of large-scale wastewater effluents were less than the odor threshold. PMID- 24225097 TI - Chemical and toxicological evaluation of transformation products during advanced oxidation processes. AB - The entry of pharmaceuticals into the water cycle from sewage treatment plants is of growing concern because environmental effects are evident at trace levels. Ozonation, UV- and UV/H(2)O(2)-treatment were tested as an additional step in waste water treatment because they have been proven to be effective in eliminating aqueous organic contaminants. The pharmaceuticals carbamazepine, ciprofloxacin, diclofenac, metoprolol and sulfamethoxazole as well as the personal care products galaxolide and tonalide were investigated in terms of degradation efficiency and by-product formation in consideration of toxic effects. The substances were largely removed from treatment plant effluent by ozonation, UV- and UV/H(2)O(2)-treatment. Transformation products were detected in all tested treatment processes. Accompanying analysis showed no genotoxic, cytotoxic or estrogenic potential for the investigated compounds after oxidative treatment of real waste waters. The results indicate that by-product formation from ozonation and advanced oxidation processes does not have any negative environmental impact. PMID- 24225098 TI - Impact of rainfall data resolution in time and space on the urban flooding evaluation. AB - Climate change and modification of the urban environment increase the frequency and the negative effects of flooding, increasing the interest of researchers and practitioners in this topic. Usually, flood frequency analysis in urban areas is indirectly carried out by adopting advanced hydraulic models to simulate long historical rainfall series or design storms. However, their results are affected by a level of uncertainty which has been extensively investigated in recent years. A major source of uncertainty inherent to hydraulic model results is linked to the imperfect knowledge of the rainfall input data both in time and space. Several studies show that hydrological modelling in urban areas requires rainfall data with fine resolution in time and space. The present paper analyses the effect of rainfall knowledge on urban flood modelling results. A mathematical model of urban flooding propagation was applied to a real case study and the maximum efficiency conditions for the model and the uncertainty affecting the results were evaluated by means of generalised likelihood uncertainty estimation (GLUE) analysis. The added value provided by the adoption of finer temporal and spatial resolution of the rainfall was assessed. PMID- 24225099 TI - Assessing the potential of a UV-based AOP for treating high-salinity municipal wastewater reverse osmosis concentrate. AB - The UVC/H(2)O(2) process was studied at laboratory scale for the treatment of one moderate (conductivity ~8 mS/cm) and two high salinity (~23 mS/cm) municipal wastewater reverse osmosis concentrate (ROC) samples with varying organic and inorganic characteristics. The process efficiency was characterized in terms of reduction of dissolved organic carbon (DOC), chemical oxygen demand (COD), colour and absorbance at 254 nm (A(254)), and the improvement of biodegradability. The reduction of colour and A(254) was significantly greater than for DOC and COD for all samples due to the greater breakdown of humic compounds, as confirmed by fluorescence excitation-emission matrix spectra. Fairly small differences in the reduction of DOC (26-38%) and COD (25-37%) were observed for all samples, suggesting that the salinity of the ROC did not have a significant impact on the UVC/H(2)O(2) treatment under the test conditions. The biodegradability of the treated ROC samples improved markedly (approximately 2-fold) after 60 min UVC/H(2)O(2) treatment. This study indicates the potential of UVC/H(2)O(2) treatment followed by biological processes for treating high-salinity concentrate, and the robustness of the process where the characteristics of the secondary effluent (influent to RO) and thus resultant ROC vary significantly. PMID- 24225100 TI - Influence of air flow rate and backwashing on the hydraulic behaviour of a submerged filter. AB - The aim of this study was to evaluate backwashing effects on the apparent porosity of the filter media and on the hydraulic behaviour of a pilot scale submerged filter, prior to biofilm colonization, under different hydraulic retention times, and different air flow rates. Tracer curves were analysed with two mathematical models for ideal and non-ideal flow (axial dispersion and Wolf and Resnick models). The filter media was lava stones sieved to 4.5 mm. Backwashing causes attrition of media particles, decreasing the void volume of the filter media and, consequently, the tracer flow is more uniform. The eroded media presented lower dead volumes (79% for the filter with aeration and 8% for the filter without aeration) compared with the new media (83% for the filter with aeration and 22% for the filter without aeration). The flow patterns of eroded and new media were different because the more regular shape of the particles decreases the void volume of the filter media. The dead volume is attributed, in the case of the filter with aeration, to the turbulence caused by the air bubbles that generate preferential channelling of the bulk liquid along the filter media, creating large zones of stagnant liquid and, for the filter without aeration, to the channels formed due to the irregular shaped media. PMID- 24225101 TI - Tracking of arsenics during the thermal stabilization of an AsH3 scrubber sludge. AB - Toxic arsenics in an AsH(3) scrubber sludge were thermally stabilized in the temperature range of 973-1,373 K. To better understand how the high-temperature treatments can stabilize arsenics in the sludge, their synchrotron X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra of arsenics were determined. It is found that the reduced arsenic leachability may be associated with the formation of As(2)O(5) (51-59%) and embedded As(V) within the Ca(3)(PO(4))(2) matrix (41-49%) in the stabilized sludge. In addition, the As-O bond distances in the stabilized As(2)O(5) are much less than that of normal As(2)O(5) by 0.05-0.07 A. The shorter As-O bond distances accompanied with the higher bonding energy also have a contribution to the thermal stabilization of arsenics. PMID- 24225102 TI - Effect of the rotifer Lecane inermis, a potential sludge bulking control agent, on process parameters in a laboratory-scale SBR system. AB - The influence of a high density of rotifers, which is known to be able to control filamentous bacteria, on the parameters of an activated sludge process was examined in four professional laboratory batch reactors. These reactors allow the imitation of the work of a wastewater treatment plant with enhanced nutrient removal. The parameters, including oxygen concentration, pH and temperature, were constantly controlled. The experiment showed that Lecane rotifers are able to proliferate in cyclically anaerobic/anoxic and aerobic conditions and at dissolved oxygen concentrations as low as 1 mg/L. In 1 week, rotifer density increased fivefold, exceeding the value of 2,200 ind./mL. The grazing activity led to an improvement in settling properties. Extremely high numbers of rotifers did not affect the main parameters, chemical oxygen demand (COD), N-NH(4), N NO(3), P-PO(4) and pH, during sewage treatment. Therefore, the use of rotifers as a tool to limit the growth of filamentous bacteria appears to be safe for the entire wastewater treatment process. PMID- 24225103 TI - Removal of phosphorus from wastewaters by biomass ashes. AB - Removal batch assays of phosphates from a synthetic wastewater (SWW) and a pulp and paper mill wastewater (PPWW) with two forestry biomass ashes were performed. The supernatants were not only chemically characterized but also the ecotoxicity was determined using two organisms: Vibrio fischeri and Artemia franciscana. The addition of fly ash and bottom ash to the SWW in solid/liquid (S/L) ratios of 3.35 and 9.05 g L(-1), respectively, achieved removal percentages of phosphates >97% for both ashes. The addition of fly ash and bottom ash to the PPWW in S/L ratios of 34.45 and 46.59 g L(-1), respectively, yield removal percentages of phosphates >90% for both ashes. According to the results of the Langmuir and Freundlich isotherms, the removal of phosphates from the SWW was mainly explained by surface removal mechanisms, while the removal from the PPWW was partially explained by multi-layer mechanisms. The supernatants resulting from the treatment of SWW and PPWW with both biomass ashes did not present acute ecotoxicity. PMID- 24225104 TI - The effects of electrode spacing on the performance of microbial fuel cells under different substrate concentrations. AB - In this study, the electricity generation and organic removal in microbial fuel cells (MFCs) were examined for electrode spacing (ES) covering 5.8, 10.2, 15.1, and 19.5 cm, and for each ES the MFCs were discharged with a series of influent substrates (COD(in)). Results indicate that organic removal was related to COD(in) but not to ES. Best chemical oxygen demand (COD) removals of 64-71% could be achieved at COD(in) around 100 mg COD/L (0.11-0.14 kg COD/m(3)-day). Best power output 3.32 mW/m(2) occurred at ES 5.8 cm and nominal COD(in) 300 mg COD/L. For every ES, the relationship of electricity generation to local substrate near anode (COD(ad)) could be adequately modeled by Monod-type kinetics. The estimated kinetic constants involve maximum current production, I(max), 15.3-19.6 mA/m(2); maximum attainable power output, P(p,max), 4.0-2.5 mW/m(2); half-saturation constant of current, K(si), 22-30 mg COD/L; and half-saturation constant of power, K(sp), 24-90 mg COD/L. This study reveals that the control over ES for improving electricity generation is dependent on the level of COD(ad), which profoundly affects the optimal design of electrode placement. PMID- 24225105 TI - Achieving nitrogen removal via nitrite pathway from urban landfill leachate using the synergetic inhibition of free ammonia and free nitrous acid on nitrifying bacteria activity. AB - In this study, a biological system consisting of an up-flow anaerobic sludge blanket (UASB) and anoxic-oxic (A/O) reactor was established for the advanced treatment of high ammonium urban landfill leachate. The inhibitory effect of free ammonia (FA) and free nitrous acid (FNA) on the nitrifying bacterial activity was used to achieve stable nitritation in the A/O reactor. The results demonstrated that the biological system achieved chemical oxygen demand (COD), total nitrogen (TN) and NH(4)(+)-N removal efficiencies of 95.3, 84.6 and 99.2%, respectively at a low carbon-to-nitrogen ratio of 3:1. Simultaneous denitritation and methanogenesis in the UASB could improve the removal of COD and TN. Nitritation with above 90% nitrite accumulation was successfully achieved in the A/O reactor by synergetic inhibition of FA and FNA on the activity of nitrite oxidizing bacteria (NOB). Fluorescence in situ hybridization (FISH) analysis showed that ammonia oxidizing bacteria (AOB) was dominant and was considered to be responsible for the satisfactory nitritation performance. PMID- 24225106 TI - Purification of inkjet ink from water using liquid phase, electric discharge polymerization and cellulosic membrane filtration. AB - A method to separate inkjet ink from water was developed using a liquid phase, electric discharge process. The liquid phase, electric discharge process with filtration or sedimentation was shown to remove 97% of inkjet ink from solutions containing between 0.1-0.8 g/L and was consistent over a range of treatment conditions. Additionally, particle size analysis of treated allyl alcohol and treated propanol confirmed the electric discharge treatment has a polymerization mechanism, and small molecule analysis of treated methanol using gas chromatography and mass spectroscopy confirmed the mechanism was free radical initiated polymerization. PMID- 24225107 TI - AOX removal from industrial wastewaters using advanced oxidation processes: assessment of a combined chemical-biological oxidation. AB - In this paper, the abatement of adsorbable halogenated organic compounds (AOX) from an industrial wastewater containing relatively high chloride concentrations by a combined chemical and biological oxidation is assessed. For chemical oxidation, the O(3)/UV, H(2)O(2)/UV and photo-Fenton processes are evaluated on pilot scale. Biological oxidation is simulated in a 4 h respirometry experiment with periodic aeration. The results show that a selective degradation of AOX with respect to the matrix compounds (expressed as chemical oxygen demand) could be achieved. For O(3)/UV, lowering the ratio of O(3) dosage to UV intensity leads to a better selectivity for AOX. During O(3)-based experiments, the AOX removal is generally less than during the H(2)O(2)-based experiments. However, after biological oxidation, the AOX levels are comparable. For H(2)O(2)/UV, optimal operating parameters for UV and H(2)O(2) dosage are next determined in a second run with another wastewater sample. PMID- 24225108 TI - Removal of As from groundwater by in situ bioprecipitation and zero-valent iron. AB - The aim of this study was to evaluate the in situ bioprecipitation (ISBP) and zero-valent iron (ZVI) for removal of arsenic from groundwater. Batch experiments were set up to test the metal/oxyanion removal efficiency using the processes induced by ZVI, by ISBP and by combining both technologies. For the construction of microcosms in anaerobic condition, aquifer material was mixed with synthetic groundwater in serum bottles. Solutions that contained commercial iron (powder, filings), iron from foundry (chips) and lactate with the carbon concentration of 0.02% (w/v) were amended. After 57 days the pH increased to 7.9 in the microcosm with lactate + iron chips. In the microcosms amended with lactate + commercial iron (powder and filings), pH was between 6.9 and 7.5 The highest decrease in sulfate concentrations was observed in the microcosm supplied with lactate (from 1,976 to 630 mg/L), and with lactate + iron filings (from 1,985 to 1,280 mg/L). The results showed that ISBP and ZVI can be efficient in the removal of As from groundwater; however, it strongly depends on the type and particle size of ZVI. The most effective was commercial ZVI. The highest decrease in As concentration was observed in the microcosm supplied with ethanol and iron powder (from 4,832 to 131 MUg/L). PMID- 24225109 TI - Production of propionic acid-enriched volatile fatty acids from co-fermentation liquid of sewage sludge and food waste using Propionibacterium acidipropionici. AB - Volatile fatty acids (VFA), derived from sludge fermentation, have been used as one effective carbon source for biological nutrient removal, especially favorable with VFA containing with high levels of propionic acid. In this paper, a new fermentation method was employed to significantly produce the propionic acid enriched VFA from the co-fermentation liquid of sewage sludge and food waste: including (1) mixing food waste with sludge in the anaerobic digester (the first stage) and (2) separating the mixture, sterilizing the first stage liquid and fermenting it after inoculation with Propionibacterium acidipropionici (the second stage). The effect of the key parameters including pH, the mixing ratio of the food waste and sludge, fermentation time and temperature of the first stage on the propionic acid-enriched VFA production (the second stage) was individually discussed. By the molecular weight distribution analysis, the comparison of the solubilisation and hydrolysis process in difference parameters was fully elaborated. The optimal combination of the parameters was then obtained. Finally, the propionic acid-enriched VFA fermentation was successfully conducted in a semi continuous reactor using the first stage liquid from the optimal condition. PMID- 24225110 TI - Paraben resistance in bacteria from sewage treatment plant effluents in India. AB - Parabens, the antimicrobial preservatives used in cosmetics, food and pharmaceuticals, are often detected in the aquatic environment. Generally, sewage treatment plants (STPs) receive community sewage containing parabens, which are ultimately released into streams/rivers. In this study, bacteria in STP effluents were evaluated for their resistance to parabens. The susceptibility was in the order of Staphylococcus aureus > Bacillus sp. >Escherichia coli > Pseudomonas aeruginosa. Gram-negative bacteria showed less susceptibility than their control and Gram-positive bacteria. Further, the bacteria were more sensitive towards butyl and ethyl parabens. Interestingly, the strains showed resistance to >=5 mg of parabens, which is equivalent to or higher than reported environmental concentrations. The increase in paraben chain length did not enhance the susceptibility in all cases and it was understood that the activity may differ for each bacterium in the environment. This is the first profile on paraben resistance in common pathogens of Indian STPs. Paraben resistance may be developed due to continuous exposure even at sub-inhibitory and/or chronic levels in the environment and this resistance may be transferred to other pathogenic bacteria in receiving waters. Thus the study demonstrates the effectiveness of the disc diffusion method in environmental bacterial resistance assessment and addresses the risk involved in the use of parabens. PMID- 24225111 TI - Adsorption of fluoride from aqueous solution by enhanced chitosan/bentonite composite. AB - In this work, enhanced chitosan/bentonite composite was prepared by treating chitosan/bentonite composite with concentrated hydrochloric acid (HCl). The adsorption of fluoride ions from aqueous solution onto the enhanced chitosan/bentonite composite was investigated. Adsorption studies were performed in a batch system, and the effects of various parameters, such as the pH value of the solution, adsorbent dosage and initial fluoride concentration, were evaluated. The optimum operating conditions for fluoride removal by the enhanced chitosan/bentonite composite were pH = 7 or so, and adsorbent dosage =1.2 g. Increasing initial fluoride concentration reduced the adsorption of fluoride onto the enhanced chitosan/bentonite composite. Furthermore, the presence of other co anions weakened the adsorption of fluoride onto this adsorbent. The equilibrium adsorption isotherms were well described by both the Freundlich and Langmuir models. The maximum monolayer adsorption capacity was 2.95 mg/g at 293 K. PMID- 24225112 TI - Simulating future trends in urban stormwater quality for changing climate, urban land use and environmental controls. AB - The effects of climatic changes, progressing urbanization and improved environmental controls on the simulated urban stormwater quality in a northern Sweden community were studied. Future scenarios accounting for those changes were developed and their effects simulated with the Storm Water Management Model (SWMM). It was observed that the simulated stormwater quality was highly sensitive to the scenarios, mimicking progressing urbanization with varying catchment imperviousness and area. Thus, land use change was identified as one of the most influential factors and in some scenarios, urban growth caused changes in runoff quantity and quality exceeding those caused by a changing climate. Adaptation measures, including the reduction of directly connected impervious surfaces (DCIS) through the integration of more green spaces into the urban landscape, or disconnection of DCIS were effective in reducing runoff volume and pollutant loads. Furthermore, pollutant source control measures, including material substitution, were effective in reducing pollutant loads and significantly improving stormwater quality. PMID- 24225113 TI - Performic acid for advanced wastewater disinfection. AB - The disinfection efficiency of performic acid (PFA) against various microbial contaminants has been studied in municipal secondary effluent. The study demonstrated that PFA provides rapid, efficient and safe disinfection, degrading both bacteria and viruses even at low doses. The resistance order starting from the most resistant microorganism is as follows: MS2-coliphages > DNA-coliphages > enterococci and Escherichia coli. PFA is also efficient in the elimination of Salmonella spp., Clostridium perfringens spores and Giardia cysts. The results showed that a PFA dose as low as 0.5-1 mg L(-1) with contact time of 10 min was efficient in achieving and maintaining for 72 h the disinfection level required for unrestricted agricultural water reuse (<=3 log units for faecal coliforms). However, the optimal dose will depend on the quality of wastewater. Regarding the formation of by-products during disinfection with PFA, very low amounts of hydrogen peroxide and organic per-acids were observed; active oxygen was not detected. The amounts of adsorbable organically bound halogens (AOX) compounds formed were significantly lower compared to the amounts generated during chlorine disinfection. This chlorine-free solution enables compliance with microbiological criteria for various water reuse applications and is already on the market for advanced disinfection. PMID- 24225114 TI - Improving the reliability of closed chamber methodologies for methane emissions measurement in treatment wetlands. AB - Non-homogeneous mixing of methane (NHM) within closed chambers was studied under laboratory conditions. The experimental set-up consisted of a PVC vented chamber of 5.3 litres of effective volume fitted with a power-adjustable 12 V fan. NHM within the chamber was studied according to fan position (top vs lateral), fan airflow strength (23 vs 80 cubic feet per minute) and the mixing time before sample withdrawal (5, 10, 15 and 20 minutes). The potential bias of methane flux densities caused by NHM was addressed by monitoring the difference between linearly expected and estimated flux densities of ca. 400, ca. 800 and ca. 1,600 mg CH(4).m(-2) d(-1). Methane within the chamber was under non-homogeneous conditions. Accordingly, methane concentrations at the bottom of the chamber were between 20 to 70% higher than those recorded at the middle or top sections of the chamber, regardless of fan position, fan air-flow strength or time before sample withdrawal. NHM led to notable biases on flux density estimation. Accordingly, flux density estimated from top and middle sampling sections were systematically lower (ca. 50%) than those expected. Flux densities estimated from bottom samples were between 10% higher and 25% lower than expected, regardless of the flux density considered. PMID- 24225115 TI - Experimental evaluation of the nitrite sensitivity coefficient in granular anammox biomass. AB - Nitrite is widely reported to inhibit anammox activity and growth. One modeling approach for nitrite impairment of anammox growth is the use of a nitrite sensitivity coefficient which increases the endogenous decay coefficient of anammox bacteria proportionally to nitrite concentration. The objective of this study was to measure nitrite concentration profiles within active anammox granules incubated at fixed bulk nitrite concentrations and to compare these with nitrite concentration profiles predicted by a biofilm model that incorporates the nitrite sensitivity coefficient. We developed an apparatus for the repeated measurement of nitrite concentration profiles along the radius of granular anammox biomass over a period of 6 days at fixed bulk nitrite concentrations. Granular anammox biomass was obtained from a two-stage bench-scale partial nitritation/anammox reactor system. There was no apparent effect of nitrite concentration on nitrite utilization kinetics after 6 days at exposures up to 90 mg NO(2)(-)-N/L. These findings suggest that anammox bacteria tolerate extended exposures to elevated nitrite concentrations, and in its present form, the nitrite sensitivity coefficient is not applicable for anammox growth modeling. PMID- 24225116 TI - Efficient cellular fractionation improves RNA sequencing analysis of mature and nascent transcripts from human tissues. AB - BACKGROUND: The starting material for RNA sequencing (RNA-seq) studies is usually total RNA or polyA+ RNA. Both forms of RNA represent heterogeneous pools of RNA molecules at different levels of maturation and processing. Such heterogeneity, in addition to the biases associated with polyA+ purification steps, may influence the analysis, sensitivity and the interpretation of RNA-seq data. We hypothesize that subcellular fractions of RNA may provide a more accurate picture of gene expression. RESULTS: We present results for sequencing of cytoplasmic and nuclear RNA after cellular fractionation of tissue samples. In comparison with conventional polyA+ RNA, the cytoplasmic RNA contains a significantly higher fraction of exonic sequence, providing increased sensitivity in expression analysis and splice junction detection, and in improved de novo assembly of RNA seq data. Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics. CONCLUSION: Our results show that cellular fractionation is a more rapid and cost effective approach than conventional polyA+ enrichment when studying mature RNAs. Thus, RNA-seq of separated cytosolic and nuclear RNA can significantly improve the analysis of complex transcriptomes from mammalian tissues. PMID- 24225117 TI - Gender difference in relationship between body mass index and development of chronic kidney disease. AB - BACKGROUND: An epidemiological approach to preventing the development or progression of chronic kidney disease (CKD) is necessary, while few effective preventive measures are currently available. We conducted a community-based, cohort study to identify the factors associated with the development of CKD in the general population. METHODS: We examined 1876 local residents of a Japanese community who had an annual health check-up and, of those, 1506 residents judged not to have CKD (473 men and 1033 women) were followed for the development of CKD over 10 years. RESULTS: The numbers of male and female residents who developed CKD during the follow-up period were 167 (35.3%) and 299 (28.9%), respectively. As compared to those without CKD development, the residents who developed CKD were older, and had a higher body mass index (BMI), systolic blood pressure, and creatinine in both genders. The rate of CKD development in obese female residents was higher than in non-obese women, but such a difference was not noted in male residents. In addition to age and serum creatinine, we identified BMI as an independently significant factor for the development of CKD in women, but not in men. CONCLUSIONS: Increased BMI is a significant risk factor for the development of CKD in women, and there seems to be a gender difference in the association between increased BMI and the development of CKD in the general population. PMID- 24225118 TI - [Alternative medicine, beliefs, and management of people with HIV in Gabon]. AB - BACKGROUND: According to WHO, 80% of the population in Africa has used alternative medicine for primary health care at least once. Gabon continues to have a high prevalence of HIV, estimated in 2011 at 5.2%. Overall, 22 253 PLWHA (people living with HIV/AIDS) - adults and children - are being treated, including 9976 on ARVs (antiretroviral drugs). The procedures for ARV initiation are very long, ARVs are frequently out of stock, and treatment in care centers for PLWHA is stigmatized: all these factors favor the development of alternative medicine for HIV care in Gabon. OBJECTIVE: To analyze the impact of alternative medicine in the treatment of PLWHA in Gabon. METHODOLOGY: This cross-sectional survey was conducted during a total of four months between May 2009 and September 2010 among PLWHA older than 18 years who had been receiving ARVs for at least 6 months and consented to participate (7 centers) and among physicians and other caregivers of these centers (8 centers). We used a simple random sample method. Epidata software was used for data collection, and the analyses were performed with SASTM software. RESULTS: Of the 5752 patients on ARVs followed at the 7 study sites, 422 PLWHA were interviewed (58.3% of them women): 284 (67.29%) in Libreville and 138 (38.7) in the provinces. Christians accounted for 90.5% (including 21.5% from Protestant evangelical churches), and Muslins for 5.68%, while 4% stated that they had no religion. 12.5% of doctors referred their patients to religious or spiritual groups. CONCLUSION: Our study showed that half of PLWHA did not know the procedures for access to ARV treatment and that beliefs about HIV/AIDS differed strongly according to place of residence. Finally, the cultural context related to alternative medicine is very present in the PLWHA treatment settings in Gabon. Although PLWHAs have easy access to ARVs, their association with organized and controlled alternative medicine can be beneficial. PMID- 24225119 TI - Restoration of horizontal stability in complete acromioclavicular joint separations: surgical technique and preliminary results. AB - BACKGROUND: Our purpose was to investigate the clinical efficacy of arthroscope assisted acromioclavicular ligament reconstruction in combination with double endobutton coracoclavicular ligament reconstruction for the treatment of complete acromioclavicular joint dislocation. METHODS: During the period from February 2010 to October 2012, ten patients with Rockwood types IV and V acromioclavicular joint dislocation were hospitalized and nine were treated with acromioclavicular ligament reconstruction combined with double endobutton of coracoclavicular ligament reconstruction. The improvement in shoulder functions was assessed using a Constant score and visual analog scale (VAS) system. RESULTS: The mean follow up period was 33.6 +/- 5.4 months. The mean Constant scores improved from 25.2 +/ 6.6 preoperatively to 92.4 +/- 6.5 postoperatively, while the mean VAS score decreased from 5.9 +/- 1.4 to 1.2 +/- 0.9; significant differences were observed. The final follow-up revealed that excellent outcomes were achieved in eight patients and good outcome in two patients. CONCLUSION: Arthroscope-assisted acromioclavicular ligament reconstruction in combination with double endobutton of coracoclavicular ligament reconstruction is an effective approach for treatment of acute complete acromioclavicular joint dislocation. PMID- 24225120 TI - Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling. AB - Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-l-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis. PMID- 24225121 TI - Effect of salinity on N2O production during shortcut biological nitrogen removal from landfill leachate. AB - Three identical SBR adapted to different salinity were applied to investigate the characteristics of the treatment performance and N2O production [Formula: see text] during shortcut biological nitrogen removal from landfill leachate under various operating parameters. Increase of salinity might deteriorate the activity of the microorganisms leading to the increase of [Formula: see text] , however, the system could be gradually adapted to the inhibition and alleviate the detrimental effect to some extent. The system acclimated to high salinity provided better performance under high salinity shock and a lower possibility of [Formula: see text] , while a sudden decrease in salinity can cause a temporary increase in [Formula: see text] . High salinity strengthened the influence of high ammonia nitrogen concentration and low DO concentration on [Formula: see text] while the strengthening effect was unconspicuous at high DO concentration. The anoxic phase did not produce a significant amount of N2O even at the lowest C/N ratio of 0.5 and was less susceptible to salinity. Characterization of the biomass composition using fluorescence in situ hybridization analysis confirmed that the relative proportion of Nitrosomonas europaea was increased with the increase of the salinity, which may be an important factor for the strengthening effect of salinity on [Formula: see text] . PMID- 24225122 TI - Renal sympathetic denervation for resistant hypertension--an alternate view. AB - Catheter-based renal denervation (RDN) is an effective treatment for resistant hypertension. But negative results with this procedure are also not uncommon. It is believed that the effectiveness of RDN is due to decreased sympathetic activity. It is suggested that the beneficial action of RDN could also at least, in part, due to restoration of balance between sympathetic and parasympathetic nervous systems. Thus, occasional negative results seen with RDN to decrease blood pressure may be attributed to failure of restoration of this balance to near normal or normal. This hypothesis explains the involvement of free radicals, immune system and nitric oxide pathways in the pathogenesis of essential hypertension since both sympathetic and parasympathetic branches of autonomic nervous system have modulatory influence on these systems. Hence, it is suggested that efforts made to augment parasympathetic tone in addition to RDN may form a more effective strategy to reduce blood pressure in resistant hypertension than RDN alone. PMID- 24225123 TI - Development of a prediction model on the acceptance of electronic laboratory notebooks in academic environments. AB - Documentation of research data plays a key role in the biomedical engineering innovation processes. It makes an important contribution to the protection of intellectual property, the traceability of results and fulfilling the regulatory requirement. Because of the increasing digitalization in laboratories, an electronic alternative to the commonly-used paper-bound notebooks could contribute to the production of sophisticated documentation. However, compared to in an industrial environment, the use of electronic laboratory notebooks is not widespread in academic laboratories. Little is known about the acceptance of an electronic documentation system and the underlying reasons for this. Thus, this paper aims to establish a prediction model on the potential preference and acceptance of scientists either for paper-based or electronic documentation. The underlying data for the analysis originate from an online survey of 101 scientists in industrial, academic and clinical environments. Various parameters were analyzed to identify crucial factors for the system preference using binary logistic regression. The analysis showed significant dependency between the documentation system preference and the supposed workload associated with the documentation system (p<0.006; odds ratio=58.543) and an additional personal component. Because of the dependency of system choice on specific parameters it is possible to predict the acceptance of an electronic laboratory notebook before implementation. PMID- 24225124 TI - Fetal behavioral states are stable over daytime - evidence by longitudinal and cross-sectional fetal biomagnetic recordings. AB - AIMS: Fetal behavioral states can be distinguished by biomagnetic recordings. We performed a longitudinal and a cross-sectional study to address the question whether the distribution of fetal behavioral states changes during the daytime. METHODS: For the longitudinal study, 32 magnetocardiographic recordings were performed on a singleton pregnancy on a weekly basis. On each examination day, two recordings were performed at different times between 25 and 40 weeks of gestation. For the cross-sectional study, fetal magnetocardiograms (fMCG) were recorded in a group of 32 singleton pregnancies matched for gestational age and daytime to the longitudinal study. The recordings were separated into two gestational age groups (less and more than 32 weeks). Fetal behavioral states were extracted from actocardiograms generated from MCG. RESULTS: No significant differences in fetal behavioral state distribution were found between morning and afternoon recordings in either the longitudinal or the cross-sectional study. CONCLUSION: This is the first magnetographic approach to show that daytime does not influence the distribution of fetal behavioral states in standardized recordings of 30 min length. This result implies that fetal magnetography recordings at normal daytimes can be combined without a bias and future recordings can be conducted independently of daytime as long as the varying behavioral states are generally taken into account during analysis. PMID- 24225125 TI - Austrian Newborn Screening Program: a perspective of five decades. AB - In 1966, the National Austrian Newborn Screening Program for inherited metabolic and endocrine disorders was initiated. In the last five decades, around four million babies were screened and in more than 2600 babies, various inborn errors of metabolism and endocrine disorders were detected. This health-preventive program was continuously expanded from phenylketonuria and galactosemia to congenital hypothyroidism, biotinidase deficiency, cystic fibrosis, and congenital adrenal hyperplasia. In 2002, the introduction of tandem mass spectrometry substantially increased the number of detectable rare diseases, and now includes disorders of fatty acid oxidation, organic acidurias, and various disorders of amino acid metabolism. In this review, we highlight the development of the Austrian screening program, and pinpoint future disorders and challenges. PMID- 24225126 TI - Etomidate with or without flumazenil anesthesia for stem cell transplantation in autistic children. AB - BACKGROUND: The aim of this study was to investigate etomidate administration with or without flumazenil in autistic children who underwent intrathecal transplantation of stem cells by lumbar puncture. METHODS: Forty autistic children aged 2-12, who were scheduled for stem cell transplantation via lumbar puncture under anesthesia, were randomized for a double-blind study. The children were randomly assigned to two groups: the flumazenil group (group F, n=20) and the etomidate group (group E, n=20). All children received 0.2 mg/kg of etomidate. In the case of inadequate anesthesia, patients received repeated doses of 0.1 mg/kg of etomidate until reaching deep sedation. After operation, children in group F were given flumazenil (0.01 mg/kg) and children in group E received placebo. Heart rate (HR), mean arterial pressure, oxygen saturation, respiratory rate, the Ramsay sedation score (RSS), and recovery time of all children were continuously monitored and recorded during the entire procedure. RESULTS: After anesthesia, blood pressure and HR measurements were not significantly changed in both groups compared with the baseline. There were no respiratory depression, bradycardia, hypotension, nausea, and vomiting. Five patients complained of pain on the site of injection. Myoclonus occurred in seven patients. Recovery time in group F was significantly shorter than in group E (p<0.001), and after the injection of flumazenil, RSS in group F significantly decreased than in group E. There were no significant differences in operation time. Physician satisfaction in both groups was similar. CONCLUSIONS: Etomidate resulted in stable hemodynamic responses and relatively less adverse effects, and flumazenil antagonized the anesthetic effect of etomidate; thus, etomidate with flumazenil is suitable for performing stem cell transplantation in autistic children. PMID- 24225127 TI - Integration of stress signals by homeodomain interacting protein kinases. AB - The family of homeodomain interacting protein kinases (HIPKs) consists of four related kinases, HIPK1 to HIPK4. These serine/threonine kinases are evolutionary conserved and derive from the yeast kinase Yak1. The largest group of HIPK phosphorylation substrates is represented by transcription factors and chromatin associated regulators of gene expression, thus transferring HIPK-derived signals into changes of gene expression programs. The HIPKs mainly function as regulators of developmental processes and as integrators of a wide variety of stress signals. A number of conditions representing precarious situations, such as DNA damage, hypoxia, reactive oxygen intermediates and metabolic stress affect the function of HIPKs. The kinases function as integrators for these stress signals and feed them into many different downstream effector pathways that serve to cope with these precarious situations. HIPKs do not function as essential core components in the different stress signaling pathways, but rather serve as modulators of signal output and as connectors of different stress signaling pathways. Their central role as signaling hubs with the ability to shape many downstream effector pathways frequently implies them in proliferative diseases such as cancer or fibrosis. PMID- 24225128 TI - A potent soluble epoxide hydrolase inhibitor, t-AUCB, modulates cholesterol balance and oxidized low density lipoprotein metabolism in adipocytes in vitro. AB - The cholesterol metabolism in adipose tissue is dependent on the balance between cholesterol uptake and efflux. Adipocytes dysfunction and its cholesterol imbalance are associated with obesity. Adipocytes are the site for clearance of oxidized low density lipoprotein (oxLDL) in blood. Soluble epoxide hydrolase (sEH) is highly expressed in adipocytes. sEH converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids, which regulate cholesterol metabolism in adipocytes and block the development of atherosclerosis. In vitro, 3T3-L1 differentiated adipocytes were incubated with the sEH inhibitor t-AUCB (0, 1, 10, 50 or 100 MUmol/l) for 24 h with or without the PPARgamma inhibitor GW9662. To determine the effect of t-AUCB on oxLDL endocytosis, degradation and cholesterol efflux from adipocytes, we demonstrated that t-AUCB enhances the CD36-mediated recognition and degradation of oxLDL and improves cholesterol efflux via the upregulation of ABCA1 expression. Furthermore, t-AUCB blocked TNF-alpha secretion and increased adiponectin levels found in adipocytes culture medium. We provide evidence that these effects are PPARgamma-dependent. These results suggest that an increase in EETs because of sEH inhibition could maintain cellular cholesterol homeostasis by the regulation of oxLDL clearance and cholesterol efflux via the EETs-PPARgamma pathway. PMID- 24225129 TI - Prism effect of specimen receiving - generation of fundamentals for the smooth progress of analytical processing. PMID- 24225130 TI - Value-added reporting of antinuclear antibody testing by automated indirect immunofluorescence analysis. AB - BACKGROUND: Automated systems for antinuclear antibody analysis are being introduced. The aim was to evaluate whether automated quantitative reading of fluorescence intensity is clinically relevant and allows for value-added reporting of test results. METHODS: Consecutive samples (n=260) were used to correlate fluorescence intensity with end-point titer. Moreover, 434 samples from controls (150 healthy blood donors, 150 chronic fatigue syndrome, and 134 diseased controls) and 252 samples (obtained at diagnosis) from patients with systemic rheumatic diseases were screened for antinuclear antibodies (1:80) on HEp-2 cells using NOVA View, and likelihood ratios were calculated for fluorescence intensity result intervals. RESULTS: There was a significant correlation between end-point titer and fluorescence intensity. Likelihood ratios for a systemic rheumatic disease increased with increasing fluorescence intensity. The likelihood ratio for a systemic rheumatic disease was 0.06, 0.18, 0.51, 5.3, and 37.5 for a fluorescence intensity of <=66, 67-150, 151-300, 301 1000, >1000, respectively. A range of 31%-37% of the patients with Sjogren's syndrome, systemic sclerosis or systemic lupus erythematosus had fluorescence intensities >1000. CONCLUSIONS: Estimation of fluorescence intensity by automated antinuclear antibody analysis offers clinically useful information. Likelihood ratios based on fluorescence intensity test result intervals aid with the interpretation of automated antinuclear antibody analysis and allow value-added reporting. PMID- 24225131 TI - S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study. AB - BACKGROUND: S100B protein measurement in blood is proposed to exclude the presence of computed tomography (CT) lesions after minor head injury (MHI). We aimed to validate S100B as an accurate and valuable screening tool for MHI diagnosis in a large multicenter study, as well as: 1) to evaluate whether a second S100B blood level determination 3 h after the first one would be informative; 2) to compare the bioclinical performances of the two commercially available automated methods of measurement of S100B for the screening of patients. METHODS: Four thousand and thirty MHI subjects were enrolled in a prospective observational multicenter study; results for serum S100B measurement determined within 3 h after the clinical event (H0) then at H3 were compared to that of cranial CT scans performed with 6 h following the presentation to emergency department. Both the Diasorin and the Roche Diagnostics assays were systematically performed. RESULTS: Cerebral lesions on CT scan were identified with sensitivity and negative-predictive value (NPV) of 96.3% and 99.4% (Diasorin, 1 dissonant case), and of 100% and 100% (Roche Diagnostics, no dissonant case). Sensitivity and NPV at H3 appeared lower than those at H0, due to the rapid decrease in S100B levels. CONCLUSIONS: Serum S100B level on admission of patients with MHI is an accurate and useful screening tool to exclude intracranial lesions. Performing a second late S100B level determination is not informative. The two automated immunoassays appear usable in a similar manner, although the two methods are not interchangeable. PMID- 24225132 TI - HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction. AB - During the last two decades a large number of computational methods have been developed for predicting transmembrane protein topology. Current predictors rely on topogenic signals in the protein sequence, such as the distribution of positively charged residues in extra-membrane loops and the existence of N terminal signals. However, phosphorylation and glycosylation are post translational modifications (PTMs) that occur in a compartment-specific manner and therefore the presence of a phosphorylation or glycosylation site in a transmembrane protein provides topological information. We examine the combination of phosphorylation and glycosylation site prediction with transmembrane protein topology prediction. We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. The method is freely available at http://bioinformatics.biol.uoa.gr/HMMpTM. PMID- 24225133 TI - A molecular phylogeny of Alpine subterranean Trechini (Coleoptera: Carabidae). AB - BACKGROUND: The Alpine region harbours one of the most diverse subterranean faunas in the world, with many species showing extreme morphological modifications. The ground beetles of tribe Trechini (Coleoptera, Carabidae) are among the best studied and widespread groups with abundance of troglobionts, but their origin and evolution is largely unknown. RESULTS: We sequenced 3.4 Kb of mitochondrial (cox1, rrnL, trnL, nad1) and nuclear (SSU, LSU) genes of 207 specimens of 173 mostly Alpine species, including examples of all subterranean genera but two plus a representation of epigean taxa. We applied Bayesian methods and maximum likelihood to reconstruct the topology and to estimate divergence times using a priori rates obtained for a related ground beetle genus. We found three main clades of late Eocene-early Oligocene origin: (1) the genus Doderotrechus and relatives; (2) the genus Trechus sensu lato, with most anisotopic subterranean genera, including the Pyrenean lineage and taxa from the Dinaric Alps; and (3) the genus Duvalius sensu lato, diversifying during the late Miocene and including all subterranean isotopic taxa. Most of the subterranean genera had an independent origin and were related to epigean taxa of the same geographical area, but there were three large monophyletic clades of exclusively subterranean species: the Pyrenean lineage, a lineage including subterranean taxa from the eastern Alps and the Dinarides, and the genus Anophthalmus from the northeastern Alps. Many lineages have developed similar phenotypes independently, showing extensive morphological convergence or parallelism. CONCLUSIONS: The Alpine Trechini do not form a homogeneous fauna, in contrast with the Pyrenees, and show a complex scenario of multiple colonisations of the subterranean environment at different geological periods and through different processes. Examples go from populations of an epigean widespread species going underground with little morphological modifications to ancient, geographically widespread lineages of exclusively subterranean species likely to have diversified once fully adapted to the subterranean environment. PMID- 24225134 TI - Copper induces--and copper chelation by tetrathiomolybdate inhibits--endothelial activation in vitro. AB - Endothelial activation with increased expression of cellular adhesion molecules and chemokines critically contributes to vascular inflammation and atherogenesis. Redox-active transition metal ions play an important role in vascular oxidative stress and inflammation. Therefore, the goal of the present study was to investigate the role of copper in endothelial activation and the potential anti inflammatory effects of copper chelation by tetrathiomolybdate (TTM) in human aortic endothelial cells (HAECs). Incubating HAECs with cupric sulfate dose- and time-dependently increased mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1). Copper also activated the redox-sensitive transcription factors, nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), which was inhibited by pretreatment of the cells with TTM. Furthermore, TTM dose-dependently inhibited tumor necrosis factor alpha (TNFalpha)-induced activation of NF-kappaB and AP-1, as well as mRNA and protein expression of VCAM 1, ICAM-1, and MCP-1, which was abolished by preincubating the cells with 5 uM TTM and 15 uM cupric sulfate. The inhibitory effect of TTM on TNFalpha-induced NF kappaB activation was associated with decreased phosphorylation and degradation of IkappaBalpha. These data suggest that intracellular copper causes activation of redox-sensitive transcription factors and upregulation of inflammatory mediators in endothelial cells. Copper chelation by TTM may attenuate TNFalpha induced endothelial activation and, hence, inhibit vascular inflammation and atherosclerosis. PMID- 24225135 TI - Following the money: copy-paste of lifestyle counseling documentation and provider billing. AB - BACKGROUND: Evidence suggests that copy-pasted components of electronic notes may not reliably reflect the care delivered. Federal agencies have raised concerns that such components may be used to justify inappropriately inflated claims for reimbursement. It is not known whether copied information is used to justify higher evaluation and management (E&M) charges. METHODS: This retrospective cohort study aimed to assess the relationship between the level of evaluation and management (E&M) charges and the method of documentation (none, distinct or copied) of lifestyle counseling (diet, exercise and weight loss) for patients with diabetes mellitus. To determine the association, an ordered multinomial logistic regression model that corrected for clustering within individual providers and patients and adjusted for patient and encounter characteristics was utilized. E&M charge level served as the primary outcome variable. Patients were included if they were followed by primary care physicians affiliated with two academic hospitals for a minimum of two years between 01/01/2000 and 12/13/2009. RESULTS: Lifestyle counseling was documented in 65.4% of 155,168 primary care encounters of 16,164 patients. Copied counseling was identified in 12,527 encounters. In multivariable analysis higher E&M charges were associated with older patient age, longer notes, treatment with insulin, medication changes and acute complaints. However, copied lifestyle counseling was associated with a decrease of 70.5% in the odds of higher E&M charge levels when time spent on counseling (required to justify higher charges based on counseling) was recorded (p<0.0001). This finding is opposite to what would have been expected if the impetus for copied documentation of lifestyle counseling was an increase in submitted E&M charges. CONCLUSION: There is no evidence that copied documentation of lifestyle counseling is used to justify higher evaluation and management charges. Higher charges were generally associated with indicators of complexity of care. PMID- 24225136 TI - Alkylphosphocholines and curcumin induce programmed cell death in cutaneous T cell lymphoma cell lines. AB - While most patients with early-stage cutaneous T-cell lymphomas (CTCL) have a very good prognosis, the survival of patients with extensive tumour stage and visceral involvement remains extremely poor and necessitates the development of more effective treatment modalities. In this study, we evaluated the in vitro effects of two alkylphosphocholines (APCs, miltefosine and erufosine) and the polyphenolic compound curcumin on 5 human CTCL cell lines (Hut-78, HH, MJ, My-La CD4+ and My-La CD8+). All tested drugs showed considerable cytotoxic activity, as determined by the MTT dye reduction assay. The IC50 values of both APCs ranged from the low micromolar level (Hut-78 cells) to 60-80MUM (HH cells). The IC50 values of curcumin ranged from 12 to 24MUM. All tested drugs induced apoptosis, as ascertained by morphological changes, DNA fragmentation and activation of caspase cascades. Miltefosine and erufosine induced dephosphorylation of Akt in My-La CD8+ cells and phosphorylation of JNK in Hut-78 and My-La CD8+ cells. APCs increased the level of the autophagic marker LC3B in Hut-78 and MJ cells. Results from co-treatment with autophagy modulators suggested that the cytotoxicity of APCs in CTCL cells is mediated, at least in part, by induction of autophagy. PMID- 24225137 TI - Overexpression of regenerating gene Ialpha appears to reflect aberration of crypt cell compartmentalization in sessile serrated adenoma/polyps of the colon. AB - BACKGROUND: Colorectal sessile serrated adenoma/polyps (SSA/Ps) are characterized by asymmetrical distribution of Ki67-positive cells, which varies among crypts and involves the crypt length to a variable extent; the pattern has been designated as aberration of crypt cell compartmentalization. The regenerating gene (REG) Ialpha is a cell growth and/or anti-apoptotic factor and its overexpression might be associated with aberration of crypt cell compartmentalization in SSA/Ps. We investigated REG Ialpha expression in SSA/Ps in comparison to hyperplastic polyps (HPs). METHODS: A total of 64 cases of serrated polyps (>= 10 mm in size), including 53 SSA/Ps and 11 HPs, were included in the present study. Immunostaining was performed using a labeled streptavidin biotin method. REG Ialpha expression was classified as follows: (i) expression of endocrine cells: grade 0 (a few positive cells) to 3 (marked increase in positive cells); (ii) expression of goblet cells: grade 0 (negative) to 2 (positive for crypts and surface epithelial cells); (iii) staining intensity of goblet cells: grade 0 (negative) to 2 (strong); (iv) staining intensity of crypt (absorptive) cell membranes: grade 0 (negative) to 2 (strong). The presence of aberration of crypt cell compartmentalization was assessed using Ki67 immunostaining. RESULTS: With regard to the REG Ialpha expression of endocrine cells, 8 out of 11 HPs (73%) were grade 0, whereas 51 of 53 SSA/Ps (96%) were grade 1 or higher (p < 0.001). With regard to the distribution of REG Ialpha-immunoreactive goblet cells, 10 of 11 HPs (91%) were grade 1, whereas 50 of 53 SSA/Ps (94%) were grade 2 (p < 0.001). A similar trend was found in the staining intensity of goblet cells or crypt cell membranes (p = 0.011). Aberration of crypt cell compartmentalization was more frequently identified in SSA/Ps (72%) than in HPs (18%; p = 0.002). A significant association was observed between REG Ialpha overexpression and the aberration of crypt cell compartmentalization in serrated polyps (p = 0.037). CONCLUSIONS: REG Ialpha overexpression is a characteristic of SSA/Ps, which appears to reflect aberration of crypt cell compartmentalization. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7240956081100040. PMID- 24225139 TI - The art of interdisciplinary teamwork. PMID- 24225140 TI - Management of pathological tooth migration in patients with advanced periodontal disease. PMID- 24225138 TI - Is a randomised controlled trial of a maternity care intervention for pregnant adolescents possible? An Australian feasibility study. AB - BACKGROUND: The way in which maternity care is provided affects perinatal outcomes for pregnant adolescents; including the likelihood of preterm birth. The study purpose was to assess the feasibility of recruiting pregnant adolescents into a randomised controlled trial, in order to inform the design of an adequately powered trial which could test the effect of caseload midwifery on preterm birth for pregnant adolescents. METHODS: We recruited pregnant adolescents into a feasibility study of a prospective, un-blinded, two-arm, randomised controlled trial of caseload midwifery compared to standard care. We recorded and analysed recruitment data in order to provide estimates to be used in the design of a larger study. RESULTS: The proportion of women aged 15-17 years who were eligible for the study was 34% (n=10), however the proportion who agreed to be randomised was only 11% (n = 1). Barriers to recruitment were restrictive eligibility criteria, unwillingness of hospital staff to assist with recruitment, and unwillingness of pregnant adolescents to have their choice of maternity carer removed through randomisation. CONCLUSIONS: A randomised controlled trial of caseload midwifery care for pregnant adolescents would not be feasible in this setting without modifications to the research protocol. The recruitment plan should maximise opportunities for participation by increasing the upper age limit and enabling women to be recruited at a later gestation. Strategies to engage the support of hospital-employed staff are essential and would require substantial, and ongoing, work. A Zelen method of post randomisation consent, monetary incentives and 'peer recruiters' could also be considered. PMID- 24225141 TI - Presurgical preparation for mandibular advancement with retromolar skeletal anchorage. PMID- 24225142 TI - A multidisciplinary approach to the management of long-face syndrome and bilateral microtia. PMID- 24225143 TI - Retreatment of an adult skeletal Class II patient. PMID- 24225144 TI - The Neoslider appliance for uprighting mesially impacted mandibular second molars. PMID- 24225145 TI - Chairside fabrication of a multipurpose power arm. PMID- 24225146 TI - Knowledge translation in Iranian universities: need for serious interventions. AB - BACKGROUND: The aim of this study was to assess the status of knowledge translation (KT) in Iranian medical science universities in order to assess the strengths and weaknesses of the most important organizations responsible for producing knowledge in the country. METHODS: The KT activities were assessed qualitatively and quantitatively in nine universities using the Self-Assessment Tool for Research Institutes. RESULTS: The strengths and weaknesses of universities were determined using seven main themes: priority setting; research quality and timeliness; researchers' KT capacities; interaction with research users; the facilities and prerequisites of KT; the processes and regulations supporting KT; and promoting and evaluating the use of evidence.The quantitative and qualitative results showed that the Iranian universities did not have an appropriate context for KT. There were significant shortcomings in supportive regulations, facilities for KT activities, and the level of interaction between the researchers and research users. CONCLUSIONS: The shortcomings in KT were mostly in the area of stewardship and policymaking (macro level), followed by planning and implementation at the universities. In order to strengthen KT in Iran, it should occupy a prominent and focused role in the strategies of the country's health research system. PMID- 24225147 TI - Kcne3 deletion initiates extracardiac arrhythmogenesis in mice. AB - Mutations in the human KCNE3 potassium channel ancillary subunit gene are associated with life-threatening ventricular arrhythmias. Most genes underlying inherited cardiac arrhythmias, including KCNE3, are not exclusively expressed in the heart, suggesting potentially complex disease etiologies. Here we investigated mechanisms of KCNE3-linked arrhythmogenesis in Kcne3(-/-) mice using real-time qPCR, echo- and electrocardiography, ventricular myocyte patch-clamp, coronary artery ligation/reperfusion, blood analysis, cardiac synaptosome exocytosis, microarray and pathway analysis, and multitissue histology. Kcne3 transcript was undetectable in adult mouse atria, ventricles, and adrenal glands, but Kcne3(-/-) mice exhibited 2.3-fold elevated serum aldosterone (P=0.003) and differentially expressed gene networks consistent with an adrenal-targeted autoimmune response. Furthermore, 8/8 Kcne3(-/-) mice vs. 0/8 Kcne3(+/+) mice exhibited an activated-lymphocyte adrenal infiltration (P=0.0002). Kcne3 deletion also caused aldosterone-dependent ventricular repolarization delay (19.6% mean QTc prolongation in females; P<0.05) and aldosterone-dependent predisposition to postischemia arrhythmogenesis. Thus, 5/11 Kcne3(-/-) mice vs. 0/10 Kcne3(+/+) mice exhibited sustained ventricular tachycardia during reperfusion (P<0.05). Kcne3 deletion is therefore arrhythmogenic by a novel mechanism in which secondary hyperaldosteronism, associated with an adrenal-specific lymphocyte infiltration, impairs ventricular repolarization. The findings highlight the importance of considering extracardiac pathogenesis when investigating arrhythmogenic mechanisms, even in inherited, monogenic channelopathies. PMID- 24225148 TI - Angiogenesis stimulated by human kallikrein-related peptidase 12 acting via a platelet-derived growth factor B-dependent paracrine pathway. AB - KLK12, a kallikrein peptidase, is thought to take part in the control of angiogenesis. Our analysis of the secretome of endothelial cells (ECs) that had been treated with KLK12 showed that KLK12 converts the extracellular matrix- or membrane-bound precursor of platelet-derived growth factor B (PDGF-B) into a soluble form. Both PDGF-B and vascular endothelial growth factor A (VEGF-A) take part in the induction of angiogenesis by KLK12 in a coculture model of angiogenesis that mimics endothelial tubule formation. We used a cellular approach to analyze the interplay between KLK12, PDGF-B, and VEGF-A and showed that release of PDGF-B by KLK12 leads to the fibroblast-mediated secretion of VEGF-A. This then stimulates EC differentiation and the formation of capillary tube-like structures. Thus, KLK12 favors the interaction of ECs and stromal cells. The released PDGF-B acts as a paracrine factor that modulates VEGF-A secretion by stromal cells, which ultimately leads to angiogenesis. Moreover, the genes encoding KLK12 and PDGFB are both expressed in ECs and up-regulated in tumor cells kept under hypoxic conditions, which is consistent with the physiological involvement of KLK12 in PDGF-B maturation. PMID- 24225149 TI - Diabetes self-management smartphone application for adults with type 1 diabetes: randomized controlled trial. AB - BACKGROUND: Persistently poor glycemic control in adult type 1 diabetes patients is a common, complex, and serious problem initiating significant damage to the cardiovascular, renal, neural, and visual systems. Currently, there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores. OBJECTIVE: The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group randomized controlled trial. METHODS: Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia. In a 6-month intervention, followed by a three month follow-up, patients (n=72) were randomized to usual care (control group) or usual care and the use of a smartphone application (Glucose Buddy) with weekly text-message feedback from a Certified Diabetes Educator (intervention group). All outcome measures were collected at baseline and every three months over the study period. Patients' glycosylated hemoglobin levels (HbA1c) were measured with a blood test and diabetes-related self-efficacy, self-care activities, and quality of life were measured with online questionnaires. RESULTS: The mean age of patients was 35.20 years (SD 10.43) (28 male, 44 female), 39% (28/72) were male, and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years (SD 9.66). Of the initial 72 patients, 53 completed the study (25 intervention, 28 control group). The intervention group significantly improved glycemic control (HbA1c) from baseline (mean 9.08%, SD 1.18) to 9-month follow-up (mean 7.80%, SD 0.75), compared to the control group (baseline: mean 8.47%, SD 0.86, follow-up: mean 8.58%, SD 1.16). No significant change over time was found in either group in relation to self-efficacy, self-care activities, and quality of life. CONCLUSIONS: In adjunct to usual care, the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000132842; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261200013284 (Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u). PMID- 24225150 TI - Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion. AB - Kisspeptin and its receptor GPR54 play a major role in trophoblast invasion, and progesterone-induced blocking factor (PIBF) is needed for maintaining pregnancy. The expression of kisspeptin/GPR54 and PIBF/progesterone receptor (PR) in trophoblasts and deciduas and the relationship between kisspeptin and PIBF were investigated in the same women with recurrent spontaneous abortion (RSA). Trophoblastic and decidual tissues were collected from 32 RSA women who miscarried a genetically normal fetus, and 35 women who had voluntary abortion. Kisspeptin, GPR54, PIBF and PR were investigated using immunohistochemistry. Kisspeptin, GPR54 and PIBF expressions in syncytiotrophoblasts and cytotrophoblasts were decreased in RSA women as compared to controls (P<0.05). Kisspeptin, PIBF and PR expressions in deciduas were significantly decreased in RSA women as compared to controls (P<0.01). GPR54 expression in deciduas nearly showed no difference between the RSA group and the control group (P=0.958). Kisspeptin and PIBF expressions in syncytiotrophoblasts, cytotrophoblasts and deciduas were correlated with each other in the RSA group (Kappa=0.602, P=0.001; Kappa=0.590, P=0.001; Kappa=0.392, P=0.011). These data support the hypothesis that decreased kisspeptin and PIBF expressions in trophoblasts and deciduas are associated with RSA. PMID- 24225151 TI - Increased container-breeding mosquito risk owing to drought-induced changes in water harvesting and storage in Brisbane, Australia. AB - BACKGROUND: Extended drought conditions in south-east Queensland during the early 2000s have resulted in a culture of water harvesting and legislated water restrictions. Aedes notoscriptus is a container-breeding mosquito vector of Ross River and Barmah Forest viruses. METHODS: From 2008-2009, the larval habitats and seasonal abundance of domestic container-breeding mosquitoes were recorded from three suburbs of Brisbane. A knowledge, attitudes and practice questionnaire was administered to householders. A low-cost, desktop methodology was used to predict the proportion of shaded premises compared with front-of-property estimates. RESULTS: We highlight changes in the frequency of container categories for A. notoscriptus as a response to human behavioural changes to drought. Garden accoutrements, discarded household items and water storage containers accounted for 66.2% (525/793) of positive containers and 77.5% (73 441/94 731) of all immature mosquitoes. Of all household premises surveyed, 52.6% (550/1046) contained rainwater tanks and 29.4% (308/1046) harvested water in other containers, contrasting with a previous 1995 survey where neither category was observed. Both Premise Condition Index and shade directly correlated with positive premises. CONCLUSIONS: Human response to drought has resulted in new habitats for domestic container-breeding mosquitoes. This recent trend of prolific water storage is similar to earlier years (1904-1943) in Brisbane when Aedes aegypti was present and dengue epidemics occurred. PMID- 24225152 TI - Personal experiences and attitudes towards intimate partner violence in healthcare providers in Guyana. AB - BACKGROUND: Intimate partner violence (IPV) is prevalent throughout the world and is a devastating public health problem. Healthcare workers (HCWs) are tasked with treating victims of IPV but may be victims themselves. Guyana is a lower-middle income country in South America. This study sought to determine the knowledge and attitudes of Guyanese HCWs and their perceived barriers to providing care in addition to determining the prevalence of IPV victimization and perpetration among HCWs. METHODS: HCWs at the only tertiary care hospital in the Guyana completed an anonymous survey that comprised 30 questions relating to IPV. RESULTS: The survey was completed by 87.5% of eligible HCWs. Of the respondents, 81.8% were female, 49.9% had ever experienced abuse and 21% admitted to perpetrating violence. Multivariate analysis found that the age groups 31-40 years (OR 2.3, 95% CI 1.1-4.6) and 41-50 years (OR 2.3, 95% CI 1.2-4.7) had higher odds of accepting justification for physical violence, and so did nursing staff (OR 4.3, 95% CI 1.4-13.1). Overall, 29.9% of HCWs accepted justification for physical violence in at least one of the named scenarios. CONCLUSION: This study demonstrates a high prevalence of IPV among HCWs and identifies prevailing attitudes regarding IPV. This knowledge is essential in developing effective, appropriate training programs and identifies a need to address IPV among the healthcare workforce. PMID- 24225153 TI - Stimulation of glucose uptake by theasinensins through the AMP-activated protein kinase pathway in rat skeletal muscle cells. AB - Theasinensins, dimeric catechins, have been reported to possess anti hyperglycemic activity, but the underlying mechanism for this activity remains unknown. In this study, the effect of theasinensins A and B on glucose uptake into rat skeletal muscle cells (L6 myotubes) was investigated. A glucose uptake study using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2 NBDG) indicated that both theasinensins A and B stimulated glucose uptake in a concentration-dependent manner and translocation of glucose transporter 4 (GLUT4) to the plasma membrane. In addition, inhibition studies measuring 2-NBDG uptake in L6 cells revealed that compound C (AMP-activated protein kinase inhibitor) suppressed theasinensin-stimulated glucose uptake, whereas genistein (insulin receptor tyrosine kinase inhibitor) and wortmannin (phosphatidylinositol 3-kinase inhibitor) were inactive. Subsequent experiments on GLUT4-related signaling pathways in L6 cells demonstrated that theasinensins promoted the phosphorylation of AMPK, but not that of Akt, and that the theasinensin-promoted glucose uptake was blocked in the presence of a CaMKK inhibitor. The promotion of AMPK phosphorylation by theasinensins was not blocked in LKB1-knockdown cells. Consequently, it was concluded that theasinensins A and B did in fact promote GLUT4 translocation to the plasma membrane in L6 myotubes through the CaMKK/AMPK signaling pathway, but not through the PI3K/Akt pathway. PMID- 24225154 TI - Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells. AB - Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-kappaB and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells. PMID- 24225155 TI - Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. AB - BACKGROUND: Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. METHODS: This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48-75 years with early breast cancer, a maximum tumour diameter of up to 2.5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1.0 cm vs 1.0-1.4 cm vs >=1.5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7.5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01849133. FINDINGS: 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5.8 years (IQR 4.1-7.7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0.0001). The 5-year event rate for IBRT was 4.4% (95% CI 2.7-6.1) in the intraoperative radiotherapy group and 0.4% (0.0-1.0) in the external radiotherapy group (hazard ratio 9.3 [95% CI 3.3 26.3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0.59). 5-year overall survival was 96.8% (95% CI 95.3-98.3) in the intraoperative radiotherapy group and 96.9% (95.5-98.3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0.0002). INTERPRETATION: Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons. FUNDING: Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation. PMID- 24225156 TI - S-1: another oral agent for patients with colorectal cancer. PMID- 24225158 TI - Intra-specific variability and biological relevance of P3N-PIPO protein length in potyviruses. AB - BACKGROUND: Pipo was recently described as a new ORF encoded within the genome of the Potyviridae family members (PNAS 105:5897-5902, 2008). It is embedded within the P3 cistron and is translated in the +2 reading frame relative to the potyviral long ORF as the P3N-PIPO fusion protein. In this work, we first collected pipo nucleotide sequences available for different isolates of 48 Potyvirus species. Second, to determine the biological implications of variation in pipo length, we measured infectivity, viral accumulation, cell-to-cell and systemic movements for two Turnip mosaic virus (TuMV) variants with pipo alleles of different length in three different susceptible host species, and tested for differences between the two variants. RESULTS: In addition to inter-specific variation, there was high variation in the length of the PIPO protein among isolates within species (ranging from 1 to 89 amino acids). Furthermore, selection analyses on the P3 cistron did not account for the existence of stop codons in the pipo ORF, but showed that positive selection was significant in the overlapping region for Potato virus Y (PVY) and TuMV. In some cases, variability in length was associated with host species, geographic provenance and/or other strain features. We found significant empirical differences among the phenotypes associated with TuMV pipo alleles, though the magnitude and sign of the effects were host-dependent. CONCLUSIONS: The combination of computational molecular evolution analyses and experiments stemming from these analyses provide clues about the selective pressures acting upon the different-length pipo alleles and show that variation in length may be maintained by host-driven selection. PMID- 24225157 TI - Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. AB - BACKGROUND: Studies done in Asia have shown that a regimen of S-1 plus oxaliplatin (SOX) has promising efficacy and safety in patients with metastatic colorectal cancer. We aimed to establish whether SOX plus bevacizumab is non inferior to mFOLFOX6 (modified regimen of leucovorin, fluorouracil, and oxaliplatin) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer. METHODS: We undertook an open-label, non-inferiority, randomised phase 3 trial in 82 sites in Japan. We enrolled individuals aged 20-80 years who had metastatic colorectal cancer, had an Eastern Cooperative Oncology Group performance status of 0 or 1, had assessable lesions, had received no previous chemotherapy or radiotherapy, could take drugs orally, and had adequate organ function. Eligible patients were randomly assigned (1:1) to receive either mFOLFOX6 plus bevacizumab (on day 1 of each 2-week cycle, 5 mg/kg intravenous infusion of bevacizumab and a simultaneous intravenous infusion of 85 mg/m(2) oxaliplatin, 200 mg/m(2)l-leucovorin, 400 mg/m(2) bolus fluorouracil, and 2400 mg/m(2) infusional fluorouracil) or SOX plus bevacizumab (on day 1 of each 3-week cycle, 7.5 mg/kg intravenous infusion of bevacizumab and 130 mg/m(2) intravenous infusion of oxaliplatin; assigned dose of S-1 twice a day from after dinner on day 1 to after breakfast on day 15, followed by 7-day break). Randomisation was done centrally with the minimisation method, with stratification by institution and whether postoperative adjuvant chemotherapy had been given. Participants, investigators, and data analysts were not masked to treatment assignment. The primary endpoint was progression-free survival (PFS), which was defined as the interval between enrolment and progressive disease (>=20% increase in sum of longest dimensions of target lesions from baseline, or appearance of new lesions) or death, whichever came first. The primary analysis was done by modified intention to treat. This trial is registered with the Japan Pharmaceutical Information Center, number JapicCTI-090699. FINDINGS: Between Feb 1, 2009, and March 31, 2011, 512 patients underwent randomisation. 256 patients assigned to receive SOX plus bevacizumab and 255 assigned to receive mFOLFOX6 plus bevacizumab were included in the primary analysis. Median PFS was 11.5 months (95% CI 10.7-13.2) in the group assigned to mFOLFOX6 plus bevacizumab and 11.7 months (10.7-12.9) in the group assigned to SOX plus bevacizumab (HR 1.04, 95% CI 0.86-1.27; less than non-inferiority margin of 1.33, pnon-inferiority=0.014). The most common haematological adverse events of grade 3 or higher were leucopenia (21 [8%] of 249 patients given mFOLFOX6 plus bevacizumab included in safety analysis vs six [2%] of 250 given SOX plus bevacizumab; p=0.0029) and neutropenia (84 [34%] vs 22 [9%]; p<0.0001). Grade 3 or higher anorexia (13 [5%] vs three [1%]; p=0.019) and diarrhoea (23 [9%] vs seven [3%]; p=0.0040) were significantly more common in patients given SOX plus bevacizumab than in those given mFOLFOX6 plus bevacizumab. We recorded seven treatment-related deaths (three in the group given mFOLFOX6 plus bevacizumab; four in that given SOX plus bevacizumab). INTERPRETATION: SOX plus bevacizumab is non-inferior to mFOLFOX6 plus bevacizumab with respect to PFS as first-line treatment for metastatic colorectal cancer, and could become standard treatment in Asian populations. FUNDING: Taiho. PMID- 24225159 TI - Alteration in lymphocyte responses, cytokine and chemokine profiles in chickens infected with genotype VII and VIII velogenic Newcastle disease virus. AB - Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus-host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM+ B cells and KUL01+ macrophages were detected in the infected spleens at 1, 3 and 4 days post infection (dpi) (P<0.05). The gene expression profiles showed an up-regulation of CCLi3, CXCLi1, CXCLi2 (IL-8), IFN-gamma, IL-12alpha, IL-18, IL-1beta, IL-6, iNOS, TLR7, MHCI, IL-17F and TNFSF13B (P<0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4dpi and caused a more rapid up-regulation of CXCLi2, IFN-gamma, IL-12alpha, IL-18, IL-1beta, iNOS and IL-10 at 3dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-gamma, IL-12alpha, IL 1beta and iNOS genes were significantly higher in AF2240 at 4dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions. PMID- 24225160 TI - Treatment of melasma in Caucasian patients using a novel 694-nm Q-switched ruby fractional laser. AB - BACKGROUND: Melasma is a common hypermelanosis of the face. The use of a classical Q-switched ruby laser (QSRL) to treat melasma is discussed controversially and is associated with frequent adverse effects, such as hyper- or hypopigmentation. Recently a fractional-mode (FRx) QSRL was developed to minimize the adverse effects of classical QSRL. The objective of this research was to evaluate the efficacy and safety of a novel FRx-QSRL in the treatment of melasma in Caucasian patients. METHODS: We performed a retrospective study of 25 Caucasian melasma patients (Fitzpatrick skin types I to III). Patients received one to three FRx-QSRL treatments (Tattoostar FRx, Asclepion Laser Technologies, Jena, Germany) at pulse energies of 4 to 8 J/cm2. Three blinded investigators independently evaluated the melasma area and severity index (MASI) score before treatment and at the four- to six-week follow-ups. At additional three-month follow-ups, patients evaluated subjective improvement, pain and over-all satisfaction with the treatment according to a numeric analogue score (NAS). Side effects were documented. RESULTS: At four to six weeks post laser treatment for a mean of 1.4 sessions, we observed a significant (P=0.0001) reduction of the MASI score from 6.54 to 1.98 (72.3%). Patients rated the pain of the intervention at a mean 2.46 points (0=no pain; 10=maximum pain), the improvement at a mean 5.55 points (0=no improvement; 10=maximum improvement) and the overall satisfaction at a mean 4.66 points (0=not satisfied; 10=maximum satisfaction). After three months, post-inflammatory hyperpigmentation (PIH) and/or recurring melasma were observed in 7 (28%) and 11 (44%) patients, respectively. CONCLUSION: The 694-nm FRx-QSRL is a safe and effective option for treating melasma in Caucasian patients. Over periods of >3 months, PIH and/or recurring melasma may develop at significant rates and may reduce patient satisfaction. Multiple treatment sessions with lower pulse energies and/or a post-interventional therapy with hypopigmenting ointments and UV protection may help to minimize these complications. PMID- 24225161 TI - Total and high molecular weight adiponectin and ethnic-specific differences in adiposity and insulin resistance: a cross-sectional study. AB - BACKGROUND: Ethnic-specific differences in insulin resistance (IR) are well described but the underlying mechanisms are unknown. Adiponectin is an insulin sensitizing adipocytokine that circulates as multiple isoforms, with high molecular weight (HMW) adiponectin associated with greatest insulin sensitivity. The objective of this study is to determine if plasma total and HMW adiponectin concentrations underlie ethnic-specific differences in IR. METHODS: Healthy Canadian Aboriginal, Chinese, European, and South Asian adults (N = 634) were assessed for sociodemographics; lifestyle; fasting plasma insulin, glucose, and total and HMW adiponectin; and adiposity measures [BMI, waist circumference, waist-to-hip ratio, percent body fat, and subcutaneous and visceral adipose tissue (quantified by computed tomography)]. The homeostasis model assessment insulin resistance (HOMA-IR) assessed IR. RESULTS: South Asians had the greatest HOMA-IR, followed by Aboriginals, Chinese, and Europeans (P < 0.001). Plasma total and HMW adiponectin concentrations were lower in Chinese and South Asians than Aboriginal and Europeans (P < 0.05). Total and HMW adiponectin were inversely associated with HOMA-IR (P < 0.001). Ethnicity modified the relationship between HMW adiponectin and HOMA-IR with stronger effects observed in Aboriginals (P = 0.001), Chinese (P = 0.002), and South Asians (P = 0.040) compared to Europeans. This was not observed for total adiponectin (P = 0.431). At mean total adiponectin concentrations South Asians had higher HOMA-IR than Europeans (P < 0.001). CONCLUSIONS: For each given decrease in HMW adiponectin concentrations a greater increase in HOMA-IR is observed in Aboriginals, Chinese, and South Asians than Europeans. Ethnic-specific differences in HMW adiponectin may account for differences in IR. PMID- 24225162 TI - 3D scaffold of PLLA/pearl and PLLA/nacre powder for bone regeneration. AB - Naturally occurring pearl and its derivatives have recently gained interest in bone regeneration due to their bioactive characteristics and good mechanical properties. In this study, three-dimensional scaffolds composed of poly-l-lactide (PLLA)/aragonite pearl powder, PLLA/vaterite pearl powder and PLLA/nacre powder were fabricated by freeze-drying. Scanning electron microscope (SEM) images indicated that the addition of powder made no visible difference to the morphology of the composite scaffolds. These composite scaffolds were found to have nearly twice the compressive strength and compressive modulus of the pure PLLA scaffold. X-ray diffraction patterns reveal that both PLLA/aragonite and PLLA/nacre composite scaffolds have pure aragonite crystals as their inorganic component, while PLLA/vaterite has pure vaterite crystals. The attachment and morphology of rat bone marrow-derived mesenchymal stem cells (rBMSCs) on scaffolds was observed by the SEM. The proliferation and osteogenic differentiation of rBMSCs on composite scaffolds was also investigated. The results indicate that PLLA/aragonite and PLLA/nacre scaffolds better stimulate cell proliferation and alkaline phosphatase activity than the PLLA scaffold. However, the PLLA/vaterite scaffold appears to decrease rBMSCs proliferation as well as the osteogenic differentiation, possibly due to the high pH of the solution containing PLLA/vaterite. PMID- 24225163 TI - Managing the vertical dimension. PMID- 24225164 TI - Master Clinician. Birte Melsen, DDS, DO. Interview by Peter M. Sinclair. PMID- 24225165 TI - Surgical-orthodontic correction of a skeletal Class III malocclusion with severe maxillary constriction. PMID- 24225166 TI - A fixed extrusion appliance for fractured anterior teeth. PMID- 24225167 TI - Repairing fractured tie wings of ceramic brackets. PMID- 24225168 TI - A biomechanical approach to second-molar intrusion. PMID- 24225169 TI - Correction of lip protrusion with lingual brackets and palatal anchorage. PMID- 24225170 TI - Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice. AB - BACKGROUND: Gout is estimated to affect 1.4% of adults in the UK. Appropriate and timely management is essential to reduce the risk of further flares, complications, and to reduce cardiovascular disease risk. The British Society for Rheumatology and British Health Professionals in Rheumatology (BSR/BHPR) and the European League Against Rheumatism (EULAR) have published guidance regarding the management of gout, thereby providing standards against which performance can be measured. This audit was designed to assess the extent to which patients diagnosed with gout in one primary care medical practice in North Staffordshire, UK, are managed in accordance with current best practice guidelines, and to identify strategies for improvement where appropriate. METHODS: Audit criteria were derived from the EULAR and BSR/BHPR guidelines; standards were set arbitrarily, but with consideration of patient comorbidity and other factors which may influence concordance. An electronic search of the practice records was performed to identify adults with a diagnosis of gout. Medical record review with a descriptive analysis was undertaken to assess the extent to which medical management adhered to the predefined standards. RESULTS: Of the total >=18 year old practice population (n = 8686), 305 (3%) patient records included a diagnosis of gout. Of these, 74% (n = 226) had an electronic record of serum uric acid (SUA), and 11% (n = 34) and 53% (n = 162) a measure of estimated glomerular filtration rate (eGFR) ever and serum glucose since diagnosis respectively. 34% (n = 105) of patients had ever taken urate-lowering therapy with 25% (n = 77) currently prescribed this at the time of data extraction. Dose adjustment and monitoring of treatment according to SUA was found to be inadequate. Provision of lifestyle advice and consideration of comorbidities was also lacking. CONCLUSIONS: The primary care management of gout in this practice was not concordant with national and international guidance, a finding consistent with previous studies. This demonstrates that the provision of guidelines alone is not sufficient to improve the quality of gout management and we identify possible strategies to increase guideline adherence. PMID- 24225171 TI - Evaluation of the educational value of YouTube videos about physical examination of the cardiovascular and respiratory systems. AB - BACKGROUND: A number of studies have evaluated the educational contents of videos on YouTube. However, little analysis has been done on videos about physical examination. OBJECTIVE: This study aimed to analyze YouTube videos about physical examination of the cardiovascular and respiratory systems. It was hypothesized that the educational standards of videos on YouTube would vary significantly. METHODS: During the period from November 2, 2011 to December 2, 2011, YouTube was searched by three assessors for videos covering the clinical examination of the cardiovascular and respiratory systems. For each video, the following information was collected: title, authors, duration, number of viewers, and total number of days on YouTube. Using criteria comprising content, technical authority, and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-useful videos. RESULTS: A total of 1920 videos were screened. Only relevant videos covering the examination of adults in the English language were identified (n=56). Of these, 20 were found to be relevant to cardiovascular examinations and 36 to respiratory examinations. Further analysis revealed that 9 provided useful information on cardiovascular examinations and 7 on respiratory examinations: scoring mean 14.9 (SD 0.33) and mean 15.0 (SD 0.00), respectively. The other videos, 11 covering cardiovascular and 29 on respiratory examinations, were not useful educationally, scoring mean 11.1 (SD 1.08) and mean 11.2 (SD 1.29), respectively. The differences between these two categories were significant (P<.001 for both body systems). The concordance between the assessors on applying the criteria was 0.89, with a kappa score >.86. CONCLUSIONS: A small number of videos about physical examination of the cardiovascular and respiratory systems were identified as educationally useful; these videos can be used by medical students for independent learning and by clinical teachers as learning resources. The scoring system utilized by this study is simple, easy to apply, and could be used by other researchers on similar topics. PMID- 24225172 TI - Melkerrson-Rosenthal Syndrome, a rare case report of chronic eyelid swelling. AB - Melkerrson-Rosenthal syndrome is a rare disorder of unknown etiology. The classical triad of recurrent facial paralysis, swelling of the face, lips and deep furrowed tongue (Lingua Plicata) is seen in very few cases, majority of the patients often present with one or two symptoms only, which often leads to misdiagnosis and mismanagement. Clinically these symptoms vary from days to years, which further delay the definitive diagnosis and symptoms may eventually become permanent. The cause of this entity is not very well understood, but thought to be attributable to multiple entities including genetic and Infectious. As this entity has been associated with numerous other clinical entities, diagnosis often remains an exclusion process. METHODS: A middle age male with a chronic history of heavy eyelids with skin indurations predominately around left eye was presented to ophthalmology clinic. Physical examination revealed a deep furrowed tongue. The skin biopsy from left eyelid revealed a non-specific granulomatous lesion. The clinical correlation of facial swelling and deep plicated tongue prompted the differential of MRS Results: Histologically a non specific granulomatous lesion was seen in dermis. As a rule, other causes of granulomatous diseases were ruled out especially Crohn's disease and sarcoidosis. Polarization failed to reveal any foreign body. CONCLUSIONS: The finding of granulomatous lesion and clinical picture led to the definite diagnosis of Melkerrson-Rosenthal syndrome. Association with rosacea was other findings. Clinically his sign and symptoms are under control and no occurrence of symptoms has been noted so far. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1647494495993706. PMID- 24225173 TI - Researching male circumcision for HIV prevention in Papua New Guinea: a process that incorporates science, faith and culture. AB - BACKGROUND: Undertaking HIV research in the culturally diverse Pacific nation of Papua New Guinea (PNG) requires careful consideration of social, cultural and religious beliefs and practices. Here, we share a detailed description of culturally informed research processes and lessons learned from the first ever study undertaken on male circumcision for HIV prevention at a faith-based university in PNG. METHODS: Male and female staff and students at Pacific Adventist University were invited to complete an anonymous self-administered questionnaire, and/or participate in a semi-structured interview or focus group discussion. Male participants were invited for clinical examination. Results were collated and disseminated to the university community in gender segregated sessions. The study deliberately partnered with student leaders and centralised social, cultural, and religious paradigms. Student leaders were interviewed about their experience of partnering in sensitive health research. RESULTS: The student leaders reported that pre-existing relationships, cultural ties, gendered sensitivity and regular communication reinforced trust between researchers, student leaders and participants, and helped the success of the study. The amount of time, complex logistics and social and cultural relationships between single and married staff and students were highlighted as challenges. CONCLUSIONS: Partnering with regional student leaders to plan and implement the study gave a legitimate and immediate mechanism for involving PNG staff and students in this sensitive health research. Gendered research processes utilised established social and cultural structures and ensured the safety of participants; all of these factors contributed to the acceptability of the study. Capacity was strengthened in PNG and Australian researchers to undertake sensitive HIV research in PNG. The study demonstrated that it is possible to conduct sensitive sexual health research at a faith-based university in PNG. PMID- 24225174 TI - Reappraisal and mindfulness: a comparison of subjective effects and cognitive costs. AB - The present study investigated the relative effects of mindfulness and reappraisal in reducing sad mood and whether trait mindfulness and habitual reappraisal moderated the effects. The study also compared the extent to which implementation of these strategies incurred cognitive resources. A total of 129 participants were randomly assigned to receiving training in mindfulness, reappraisal, or no training prior to undergoing an autobiographical sad mood induction. Results showed that mindfulness and reappraisal were superior to no training, and equivalent in their effects in lowering sad mood. Compared to mindfulness, reappraisal resulted in significantly higher interference scores on a subsequent Stroop test, reflecting greater depletion of cognitive resources. Higher trait mindfulness, but not habitual reappraisal, predicted greater reductions in sadness across conditions. The study suggests that although mindfulness and reappraisal are equally effective in down-regulating sad mood, they incur different levels of cognitive costs. PMID- 24225175 TI - Children with limited oral opening can be safely managed without a tracheostomy. AB - OBJECTIVE: To describe airway management of children with limited oral opening that does not allow for routine orotracheal intubation by direct laryngoscopy. To analyze the incidence and outcome of airway compromise or loss in patients without a tracheostomy in place. STUDY DESIGN: Case series with chart review. SETTING: Tertiary children's hospital. SUBJECTS: Children with limited oral opening that does not allow for routine orotracheal intubation. METHODS: Children treated at Children's Hospitals and Clinics of Minnesota from 1997 to 2012 with severe trismus were identified and included in the study. Hospital and clinic records were reviewed. RESULTS: Ten children (mean age, 13 years; range, 7-17 years) were identified for inclusion into the study. A total of 109 operations requiring general anesthesia (average of 10.9 per patient; range, 0-23) were performed on patients without a tracheostomy in place. Flexible fiber-optic nasotracheal intubation was performed in 58 cases. The remainder of airway control was by mask ventilation (33 cases), various methods of orotracheal intubation (10 cases), unknown (6 cases), and laryngeal mask airway (2 cases). There was a total of 118 patient-years of follow-up without a tracheostomy tube in place (average of 11.8 years per patient). During this period, there were no episodes of acute airway compromise that resulted in neurologic deficits. CONCLUSION: Children with limited oral opening that does not allow for routine orotracheal intubation with direct laryngoscopy may be safely managed without a tracheostomy, even when the child requires frequent procedures under general anesthesia. PMID- 24225176 TI - The astroglial reaction along the mouse cochlear nerve following inner ear damage. AB - OBJECTIVE: Determine how the astroglial cells of the peripheral and central nervous system transitional zone (PCTZ) react to sensorineural hearing loss using a mouse cochlear nerve model. STUDY DESIGN: Prospective, basic science. SETTING: Research laboratory. SUBJECTS AND METHODS: Neomycin was injected into the mouse inner ear to cause chemically induced hearing loss. Auditory brainstem responses (ABRs) were used to determine hearing threshold shifts after neomycin treatment. Immunofluorescence was used to detect the expression of proteins specific for hair cells, spiral ganglion neurons, astrocytes, and the myelin components of both oligodendrocytes and Schwann cells. RESULTS: ABR threshold shifts and immunofluorescence results supported that hair cells and spiral ganglion neurons were damaged in neomycin-treated mice. Immunofluorescence showed the peripheral and central nervous system (PNS and CNS) transitional zone of the cochlear nerve at the interface of the myelin components of the PNS and CNS. In the control mice, the expression of glial fibrillary acidic protein (GFAP) was observed proximally to the PCTZ closer to the CNS, which is their normal location. However, in neomycin-treated animals the expression of GFAP was detected distally to the PCTZ and was found close to the spiral lamina level in the basal cochlear turn, suggesting that GFAP-expressing astrocytes migrated across the PCTZ and reached the PNS. CONCLUSION: The GFAP positive astrocyte processes extended across the PCTZ along the mouse cochlear nerve following chemically induced sensorineural hearing loss. PMID- 24225177 TI - Maxillary swing: the paramedian palatal incision. PMID- 24225178 TI - Genome-wide analysis and evolutionary study of sucrose non-fermenting 1-related protein kinase 2 (SnRK2) gene family members in Arabidopsis and Oryza. AB - The over-expression of plant specific SnRK2 gene family members by hyperosmotic stress and some by abscisic acid is well established. In this report, we have analyzed the evolution of SnRK2 gene family in different plant lineages including green algae, moss, lycophyte, dicot and monocot. Our results provide some evidences to indicate that the natural selection pressure had considerable influence on cis-regulatory promoter region and coding region of SnRK2 members in Arabidopsis and Oryza independently through time. Observed degree of sequence/motif conservation amongst SnRK2 homolog in all the analyzed plant lineages strongly supported their inclusion as members of this family. The chromosomal distributions of duplicated SnRK2 members have also been analyzed in Arabidopsis and Oryza. Massively Parallel Signature Sequencing (MPSS) database derived expression data and the presence of abiotic stress related promoter elements within the 1 kb upstream promoter region of these SnRK2 family members further strengthen the observations of previous workers. Additionally, the phylogenetic relationships of SnRK2 have been studied in all plant lineages along with their respective exon-intron structural patterns. Our results indicate that the ancestral SnRK2 gene of land plants gradually evolved by duplication and diversification and modified itself through exon-intron loss events to survive under environmental stress conditions. PMID- 24225180 TI - SELDI-TOF analysis of glioblastoma cyst fluid is an approach for assessing cellular protein expression. AB - OBJECTIVES: In about 10% of glioblastoma patients, preoperative MRI discloses the presence of tumor cysts. Whereas the impact of cystic appearance on prognosis has been discussed extensively, only little is known about the tumor cyst fluid. In this study, we tested the feasibility of the surface enhanced laser desorption ionization time of flight (SELDI-TOF) technique to detect cyst fluid proteins. METHODS: Cyst fluid was collected from 21 glioblastoma patients for SELDI-TOF analysis and compared to control cerebrospinal fluids from 15 patients with spinal stenosis. Resulting protein peaks with significant differences between groups were further described, using the molecular weight in an internet search of protein databases and publications. Two potential cyst fluid proteins, basigin and ferritin light chain, were selected for immunohistological detection in the histologic slides of the patients, metallothionein (MT) served as negative control. RESULTS: As supposed from the results of the SELDI-TOF analysis, basigin and ferritin were detected immunohistochemically in the cyst wall, whereas MT was more equally distributed between the cyst wall and the surrounding tumor tissue. Median survival time of the patients was 20 months (range 2 to 102 months) and correlated with age, but not with expression of the three proteins. DISCUSSION: The SELDI-TOF approach reveals a number of proteins, potentially present in glioblastoma cyst fluid. Identification of these proteins in tumor cells may help understand the pathogenetic pathways and the prognostic value of cystic changes. PMID- 24225179 TI - PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to beta-adrenergic signaling. AB - beta-Adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca(2+) handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50=10.6+/-0.7 min; EC50=89.0 nmol/L) than in the cytosol (t50=3.71+/-0.25 min; EC50=1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca(2+) and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50=1.84 nmol/L) over cell hypertrophy (EC50=85.9 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile beta-adrenergic signaling responses. PMID- 24225181 TI - Zinc oxide nanoparticles provide an adjuvant effect to ovalbumin via a Th2 response in Balb/c mice. AB - Zinc oxide nanoparticles (ZNPs) have been used in dietary supplements and may cause an immunomodulatory effect. The present study investigated the effect of ZNPs on antigen-specific immune responses in mice sensitized with the T-cell dependent antigen ovalbumin (OVA). BALB/c mice were intraperitoneally administered ZNPs (0.25, 0.5, 1 and 3mg) once, in combination with OVA, and the serum antibodies, splenocyte reactivity and activation of antigen-presenting cells were examined. The serum levels of OVA-specific IgG1 and IgE were found significantly enhanced by treatment with ZNPs over control. An increased level of IL-2, IL-4, IL-6, IL-17 and decreased level of IL-10 and TNF-alpha in splenocytes administered with ZNPs were observed in comparison with control. The ZNPs and OVA stimulated T lymphocytes showed enhanced proliferation compared with control. Macrophages and B cells showed high expression of MHC class II, whereas higher expression of CD11b in macrophages of the ZNPs and ZNPs/OVA treated groups was observed. The lungs and spleen had increased eosinophils and mast cell numbers. Also, myeloperoxidase activity in lungs was found to be increased by 2.5-fold in the case of ZNPs and 3.75-fold increase in ZNPs/OVA, whereas in intestine, there was significant increase in both the groups. Increased expression of the genes for GATA-3, SOCS-3, TLR-4, IL-13 and IL-5 in the intestine was observed. Collectively, these data indicate that systemic exposure to a single administration of ZNPs could enhance subsequent antigen-specific immune reactions, including the serum production of antigen-specific antibodies, and the functionality of T cells. PMID- 24225182 TI - Tubular scaffolds of gelatin and poly(epsilon-caprolactone)-block-poly(gamma glutamic acid) blending hydrogel for the proliferation of the primary intestinal smooth muscle cells of rats. AB - The proper regeneration of intestinal muscle for functional peristalsis is the most challenging aspect of current small intestine tissue engineering. This study aimed to fabricate a hydrogel scaffold for the proliferation of intestinal smooth muscle cells (ISMCs). Tubular porous scaffolds of 10-20 wt% gelatin and 0.05-0.1 wt% poly(epsilon-caprolactone)-block-poly(gamma-glutamic acid) blending hydrogel were cross-linked by carbodiimide and succinimide in an annular space of a glass mold. The scaffolds with higher gelatin contents degraded slower in the phosphate buffer solution. In rheological measurements, the hydrated scaffolds were elastic (all tangent delta <0.45); they responded differentially to frequency, indicating a complete viscoelastic property that is beneficial for soft tissue regeneration. Isolated rat ISMCs, with the characteristic biomarkers alpha-SMA, calponin and myh11, were loaded into the scaffolds by using either static or centrifugal methods. The average cell density inside the scaffolds increased in a time dependent manner in most scaffolds of both seeding groups, although at early time points (seven days) the centrifugal seeding method trapped cells more efficiently and yielded a higher cell density than the static seeding method. The static seeding method increased the cell density from 7.5-fold to 16.3-fold after 28 days, whereas the centrifugal procedure produced a maximum increase of only 2.4 fold in the same period. In vitro degradation data showed that 50-80% of the scaffold was degraded by the 14th day. However, the self-secreted extracellular matrix maintained the integrity of the scaffolds for cell proliferation and spreading for up to 28 days. Confocal microscopic images revealed cell-cell contacts with the formation of a 3D network, demonstrating that the fabricated scaffolds were highly biocompatible. Therefore, these polymeric biomaterials hold great promise for in vivo applications of intestinal tissue engineering. PMID- 24225183 TI - Could the patient have been seen by a nurse; a questionnaire based survey of GP and patient views in Danish general practice. AB - BACKGROUND: Nurses in Denmark have been increasingly involved in general practice care, which may have implications for the role of the general practitioner (GP) and patients' experience of primary care. The aim of this study was to explore possibilities of doctor-nurse substitution seen from GP and patient perspectives and patient preferences in regard to consultations with a personal GP. METHODS: The study was based on data from a Danish survey on disease patterns in general practice (KOS 2008). Background information on patients and GPs was linked with their responses to whether a nurse could have substituted the GP in consultations and patient-assessed importance of seeing a personal GP. Associations were measured with prevalence rate ratio (PR). RESULTS: Doctor-nurse substitution was a possibility in 14.8% of consultations according to GPs and in 11.7% according to patients. GP and patient agreed on substitution in 3.5% of consultations (Kappa = 0.164). Follow-up consultations were more often feasible for substitution than new episode according to GPs (adj. PR = 2.06 (1.62-2.62)), but not according to patients (adj. PR = 1.02 (0.64-1.33)). Follow-up consultations were related to high importance of seeing the personal GP (adj. PR = 1.18 (1.05 1.33). For both patients and GPs, consultations with patients with chronic conditions were not significantly associated with nurse substitution. Male and younger patients did more often suggest substitution than women and older patients. For GPs, increasing patient age was associated with relevance of substitution. Patients who found it 'very important' to see their personal GP were less likely to consider nurse substitution a possibility (adj. PR = 0.57 (0.45-0.71). CONCLUSIONS: GPs and patients found nurse substitution relevant in more than one in ten consultations, although they rarely agreed on which consultations. Follow-up consultations and consultations with older patients were associated with GPs considering nurse substitution appropriate more often. For patients, male and younger patients most often found substitution relevant. High importance of seeing the personal GP may contribute to patient reluctance to nurse substitution, especially for follow-up consultations. The results indicate a need for involving patients' perspective when altering the future roles of primary health care professionals. PMID- 24225184 TI - Equivalence of Gyn GEC-ESTRO guidelines for image guided cervical brachytherapy with EUD-based dose prescription. AB - BACKGROUND: To establish a generalized equivalent uniform dose (gEUD) -based prescription method for Image Guided Brachytherapy (IGBT) that reproduces the Gyn GEC-ESTRO WG (GGE) prescription for cervix carcinoma patients on CT images with limited soft tissue resolution. METHODS: The equivalence of two IGBT planning approaches was investigated in 20 patients who received external beam radiotherapy (EBT) and 5 concomitant high dose rate IGBT treatments. The GGE planning strategy based on dose to the most exposed 2 cm3 (D2cc) was used to derive criteria for the gEUD-based planning of the bladder and rectum. The safety of gEUD constraints in terms of GGE criteria was tested by maximizing dose to the gEUD constraints for individual fractions. RESULTS: The gEUD constraints of 3.55 Gy for the rectum and 5.19 Gy for the bladder were derived. Rectum and bladder gEUD-maximized plans resulted in D2cc averages very similar to the initial GGE criteria. Average D2ccs and EUDs from the full treatment course were comparable for the two techniques within both sets of normal tissue constraints. The same was found for the tumor doses. CONCLUSIONS: The derived gEUD criteria for normal organs result in GGE-equivalent IGBT treatment plans. The gEUD-based planning considers the entire dose distribution of organs in contrast to a single dose volume-histogram point. PMID- 24225186 TI - Potential: the valuation of imagined future achievement. AB - The concept of potential is central to a number of decisions, ranging from organizational hiring, to athletic recruiting, to the evaluation of artistic performances. While potential may often be valued for its future payoffs, the present studies investigate whether people value potential even when making decisions about goods and experiences that can only be consumed in the present. Experiment 1 demonstrates that potential makes people more likely to consume inferior performances in the present. Experiment 2 manipulated temporal focus and demonstrates that focusing on the present (vs. the future) attenuates the effect of potential on enjoyment. Experiment 3 demonstrates that merely moving the performance into the past negates the effect of potential. And, Experiment 4 demonstrates that potential increases valuation only when value is tied to abstract, hedonic dimensions, but not when it is tied to concrete, utilitarian dimensions. PMID- 24225185 TI - Expression changes of ribosomal proteins in phosphate- and iron-deficient Arabidopsis roots predict stress-specific alterations in ribosome composition. AB - BACKGROUND: Ribosomes are essential ribonucleoprotein complexes that are engaged in translation and thus indispensable for growth. Arabidopsis thaliana ribosomes are composed of 80 distinct ribosomal proteins (RPs), each of which is encoded by two to seven highly similar paralogous genes. Little information is available on how RP genes respond to a shortage of essential mineral nutrients such as phosphate (Pi) or iron (Fe). In the present study, the expression of RP genes and the differential accumulation of RPs upon Pi or Fe deficiency in Arabidopsis roots were comprehensively analyzed. RESULTS: Comparison of 3,106 Pi-responsive genes with 3,296 Fe-responsive genes revealed an overlap of 579 genes that were differentially expressed under both conditions in Arabidopsis roots. Gene ontology (GO) analysis revealed that these 579 genes were mainly associated with abiotic stress responses. Among the 247 RP genes retrieved from the TAIR10 release of the Arabidopsis genome (98 small subunit RP genes, 143 large subunit RP genes and six ribosome-related genes), seven RP genes were not detected in Arabidopsis roots by RNA sequencing under control conditions. Transcripts from 20 and 100 RP genes showed low and medium abundance, respectively; 120 RP genes were highly expressed in Arabidopsis roots. As anticipated, gene ontology (GO) analysis indicated that most RP genes were related to translation and ribosome assembly, but some of the highly expressed RP genes were also involved in the responses to cold, UV-B, and salt stress. Only three RP genes derived from three 'sets' of paralogous genes were differentially expressed between Pi-sufficient and Pi-deficient roots, all of which were induced by Pi starvation. In Fe deficient plants, 81 RP genes from 51 'sets' of paralagous RP genes were significantly down-regulated in response to Fe deficiency. The biological processes 'translation' (GO: 0006412), 'ribosome biogenesis (GO: 0042254), and 'response to salt (GO: 0009651), cold (GO: 0009409), and UV-B stresses (GO: 0071493)' were enriched in this subset of RP genes. At the protein level, 21 and two RPs accumulated differentially under Pi- and Fe-deficient conditions, respectively. Neither the differentially expressed RP genes nor the differentially expressed RPs showed any overlap between the two growth types. CONCLUSIONS: In the present study three and 81 differentially expressed RP genes were identified under Pi and Fe deficiency, respectively. At protein level, 21 and two RP proteins were differentially accumulated under Pi- and Fe-deficient conditions. Our study shows that the expression of paralogous genes encoding RPs was regulated in a stress-specific manner in Arabidopsis roots, presumably resulting in an altered composition of ribosomes and biased translation. These findings may aid in uncovering an unexplored mechanism by which plants adapt to changing environmental conditions. PMID- 24225187 TI - MicroRNA-gene signaling pathways in pancreatic cancer. AB - Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients. PMID- 24225188 TI - Chronic allograft dysfunction: a model disorder of innate immunity. AB - The innate immune system is a highly sensitive organ of perception sensing any cell stress and tissue injury. Its major type of response to all potential inciting and dangerous challenges is inflammation and tissue repair and, if needed, induction of a supportive adaptive immune response, the aim always being to maintain homeostasis. However, although initially beneficial, innate immunity mediated, protection-intended repair processes become pathogenic when they are exaggerated and uncontrolled, resulting in permanent fibrosis which replaces atrophic or dying tissue and may lead to organ dysfunction or even failure. In this sense, atherosclerosis and organ fibrosis reflect classical disorders caused by an overreacting innate immune system. Strikingly, these two pathologies dominate the development of chronic allograft dysfunction as the main clinical problem still left in transplantation medicine. Growing evidence suggests that acute and chronic allograft injuries, including alloimmune-, isoimmune-, nonimmune-, and infection-mediated insults, not only lead to cell death associated graft atrophy but also activate the innate immune system which, over time, leads to uncontrolled intragraft fibrogenesis, thereby compromising allograft function. Acute and chronic allograft injuries lead to induction of damage-associated molecular patterns (DAMPs) which, after recognition by pattern recognition receptors, activate cells of the innate immune system such as donor derived intragraft fibroblasts and vascular cells as well as recipient-derived graft-invading macrophages and leukocytes. It is mainly the orchestrated action and function of these cells that slowly but steadily metamorphose the originally life-saving allograft into a poorly functioning organ of marginal viability. PMID- 24225189 TI - Cisplatin, tegafur-uracil and leucovorin plus mitomycin C: an acceptably effective and toxic regimen for patients with recurrent or metastatic nasopharyngeal carcinoma. AB - BACKGROUND: This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma. METHODS: Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m(2) on day 1, 22 and mitomycin C 6 mg/m(2) on day 1 were administered. Oral tegafur-uracil 300 mg/m(2)/day and oral leucovorin 60 mg/day were given on day 1 14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively. RESULTS: Twenty-two patients with the median age of 47 (35-69) years were enrolled in the study. Sixteen (72.7%) patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6%) who experienced grade IV anorexia, and two patients (9.1%) who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6%) complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months. CONCLUSION: This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma. PMID- 24225190 TI - Ultrasound localization of the femoral vein facilitates successful cannulation for hemodialysis. AB - BACKGROUND: Real-time ultrasound-guided techniques allow for improved cannulation of the internal jugular vein and femoral vein for hemodialysis; however, these techniques require extra sterilization procedures, specialized probes, or needle guides. A simpler ultrasound vessel localization method was performed to investigate whether this alternative approach would aid in the cannulation of the femoral vein for patients in whom temporary angioaccess was required for hemodialysis. METHODS: Patients requiring temporary femoral vein catheters for hemodialysis were divided into 2 groups on alternating days of the week during a 6-month period. One group underwent ultrasound localization of the femoral vein before cannulation and the second group received conventional landmark localization. Data regarding the strength of the femoral arterial pulse, number of attempts, failures, and complications were recorded. RESULTS: Ultrasound localization resulted in significantly improved first-attempt success rates, reduced attempts, and reduced failure and complication rates overall (p < 0.001, p < 0.001, p = 0.002 and p = 0.004 respectively) as well as in the group of patients with a clearly discernible arterial pulse (p < 0.001, p = 0.001, p = 0.004 and p = 0.011 respectively). The same trend was observed among patients with faintly palpable or non-palpable femoral arterial pulses, although the differences were not statistically significant. CONCLUSION: Cannulation of the femoral vein for hemodialysis should be performed with the aid of ultrasound. If real-time ultrasound-guided cannulation is not available, the vessel localization method is a good alternative, given its known limitations and the fact that it is simpler. It remains to be determined whether 1 - dimensional localization or localization including vessel depth information can improve outcomes in patients with faintly palpable or non-palpable femoral arterial pulses. PMID- 24225191 TI - Health related quality of life of long-term kidney transplantation recipients. AB - BACKGROUND: Health related quality of life (HRQOL) is an important issue for long term kidney transplantation (KT) patients. Nevertheless, few studies have focused on long-term HRQOL in KT recipients with a functional graft. Thus, the aim of this study is to describe the long-term (10-year) HRQOL of KT recipients. METHODS: This is a cross-sectional and correlational design. The Medical Outcome Survey (MOS SF-36) questionnaire was used to collect data on HRQOL. The data were collected from November 2009 to September 2010 at a medical center in Northern Taiwan. RESULTS: A total of 88 patients were interviewed. The mean years after transplantation was 14.48 (SD = 3.9). The mean score of each of the HRQOL subscales ranged from 59.4 to 82.5. The mean scores on the bodily pain (BP) subscale were the highest and, on the general health (GH) subscale, the lowest. Compared to the general population, with the exception of the BP subscale, long term KT patients had a lower mean score (poorer HRQOL) on all subscales. Age, gender, serum creatinine level, and employment status were significantly related to HRQOL. CONCLUSION: HRQOL of long-term KT patients was, overall, poorer than that of the general population. When comparing the HRQOL of KT patients with that of the general population, one should take into account age and gender. Finally, the physical, psychological, and social adjustment domains of HRQOL of KT patients warrant further attention. PMID- 24225192 TI - Assessment of videoendoscopy-assisted abdominoplasty for diastasis recti patients. AB - BACKGROUND: The objective of this retrospective analysis was to assess the treatment of endoscope abdominoplasty for diastasis recti deformity patients. METHODS: From January 1999 to January 2011, 88 patients ranging from 35 to 46 years in age were treated with videoendoscopy-assisted minimally invasive surgery. All patients were Asian. Early (< 3 months) and late (> 6 months) complications were assessed throughout a follow-up period of up to 66 months. RESULTS: Observations were conducted at the end of three weeks, six months, and 66 months. Early on, all patients experienced numbness with local paresthesia (100%) closely after treatment, and reported the feelings to subside by six months post-treatment. Four patients (4.5%) experienced ecchymosis, and three patients (3.4%) were affected by seroma. One patient (1.1%) had dyspnea immediately after surgery, which recovered after oxygen (O2) administration. Only one patient (1.1%) experienced minimal skin loss, which recovered after 3 months of surgery, and there were no further complications. Hypertrophic scars were apparent in three patients (3.4%) who showed no unwanted signs or further complications after post-operative scar care. No hematoma had been reported. All complications subsided (> 6 months) postoperatively. CONCLUSIONS: Videoendoscopy assisted abdominoplasty can be used for diastasis recti deformity with minimal excess skin. Our study demonstrated effects against the formation of seroma and other complications. PMID- 24225193 TI - From polychemotherapy regimens to molecular targeting strategies. PMID- 24225194 TI - Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury. AB - BACKGROUND: ARA290 is a non-erythropoietic EPO derivative which only binds to the cytoprotective receptor complex (EPOR2-betacR2) consisting of two EPO-receptors (EPOR) and two beta common receptors (betacR). ARA290 is renoprotective in renal ischemia/reperfusion (I/R). In a renal I/R model we focussed on timing of post reperfusional administration of ARA290. Furthermore, we investigated the anti inflammatory properties of ARA290. METHODS: Twenty-six male Lewis/HanHsd rats were exposed to unilateral ischemia for 30 minutes, with subsequent removal of the contralateral kidney. Post-reperfusion, ARA290 was administered early (one hour), late (four hours) or repetitive (one and four hours). Saline was used as vehicle treatment. Rats were sacrificed after three days. RESULTS: Early ARA290 treatment improved renal function. Late- or repetitive treatment tended to improve clinical markers. Furthermore, early ARA290 treatment reduced renal inflammation and acute kidney injury at three days post-reperfusion. Late- or repetitive treatment did not affect inflammation or acute kidney injury. CONCLUSIONS: ARA290 attenuated renal ischemia/reperfusion injury. This study showed the anti-inflammatory effect of ARA290 and suggests early administration in the post-reperfusional phase is most effective. ARA290 is a candidate drug for protection against ischemic injury following renal transplantation. PMID- 24225195 TI - Assessing radiotracer kinetics in the Langendorff perfused heart. AB - BACKGROUND: The Langendorff perfused heart is a physiologically relevant and controllable model with potential for assessing the pharmacokinetics of new radiotracers under a range of pathophysiological conditions.. We assess the feasibility of extending the methods validated for in vivo PET data analysis to the characterisation of PET tracer kinetics applied to Langendorff perfused hearts. METHODS: Monte Carlo simulations were used to study the accuracy and reproducibility of linear and non-linear spectral analysis (SA/NLSA), the Patlak graphical method and normalised tissue activity (NA). The methods were used to analyse time-activity curves of two widely used PET tracers, [18 F]-FDG and [18 F]-FMISO, acquired ex vivo from Langendorff perfused rat hearts under normoxic and hypoxic conditions. RESULTS: Monte Carlo simulations showed NLSA to be superior to SA in identifying and quantifying the presence of irreversible trapping component (alphao), for low values of alphao. The performance of NLSA and SA for high values of trapping was comparable. NLSA was also more precise than SA in determining the absence of trapping over the range of simulated kinetics and SNR. Simulations also suggest that the semi-quantitative method NA is adequate for the evaluation of trapping, and it was found to be more accurate than Patlak. The values of alpha0 estimated with NLSA from the time series of both [18 F]-FDG and [18 F]-FMISO increased significantly from normoxia to hypoxia in agreement with previous studies. The values of trapping derived using SA increased but not significantly, reflecting the larger error associate with this method. Patlak estimated from the experimental datasets increased from normoxia to hypoxia but was not significant. NA estimated from the [18 F]-FDG data increased from normoxia to hypoxia, but was not significant, whilst NA calculated for [18 F]-FMISO time-activity curves increased significantly. CONCLUSIONS: Monte Carlo simulations suggested that spectral-based quantitative analysis methods are adequate for the kinetic characterisation of time-activity curves acquired ex vivo from perfused hearts. The uptake rate Patlak and the index NA also represent a good alternative to the SA and NLSA algorithms when the aim of the kinetic analysis is to measure changes in the amount of tracer trapped in the irreversible compartment in response to external stimuli. For low levels of trapping, NLSA and NA were subject to lower errors than SA and Patlak, respectively. PMID- 24225196 TI - Novel biologically-inspired rosette nanotube PLLA scaffolds for improving human mesenchymal stem cell chondrogenic differentiation. AB - Cartilage defects are a persistent issue in orthopedic tissue engineering where acute and chronic tissue damage stemming from osteoarthritis, trauma, and sport injuries, present a common and serious clinical problem. Unlike bone, cartilage repair continues to be largely intractable due to the tissue's inherently poor regenerative capacity. Thus, the objective of this study is to design a novel tissue engineered nanostructured cartilage scaffold via biologically-inspired self-assembling rosette nanotubes (RNTs) and biocompatible non-woven poly (l lactic acid) (PLLA) for enhanced human bone marrow mesenchymal stem cell (hMSC) chondrogenic differentiation. Specifically, RNTs are a new class of biomimetic supramolecular nanomaterial obtained through the self-assembly of low-molecular weight modified guanine/cytosine DNA base hybrids (the G?C motif) in an aqueous environment. In this study, we synthesized a novel twin G?C-based RNT (TB-RGDSK) functionalized with cell-favorable arginine-glycine-aspartic acid-serine-lysine (RGDSK) integrin binding peptide and a twin G?C based RNT with an aminobutane linker molecule (TBL). hMSC adhesion, proliferation and chondrogenic differentiation were evaluated in vitro in scaffold groups consisting of biocompatible PLLA with TBL, 1:9 TB-RGDSK:TBL, and TB-RGDSK, respectively. Our results show that RNTs can remarkably increase total glycosaminoglycan, collagen, and protein production when compared to PLLA controls without nanotubes. Furthermore, the TB-RGDSK with 100% well-organized RGDSK peptides achieved the highest chondrogenic differentiation of hMSCs. The current in vitro study illustrated that RNT nanotopography and surface chemistry played an important role in enhancing hMSC chondrogenic differentiation thus making them promising for cartilage regeneration. PMID- 24225197 TI - Involvement of alpha7 nAChR subtype in rat oxaliplatin-induced neuropathy: effects of selective activation. AB - Oxaliplatin, unlike other platinum anticancer agents, has only mild toxic effects on the hematopoietic, urinary and gastrointestinal systems. Its dose-limiting side effect is neurotoxicity that may evolve to a neuropathic syndrome which is difficult to treat. In this study we treated rats with oxaliplatin (2.4 mg/kg/day intraperitoneally, for 3 weeks), and observed that expression levels of the alpha7 nicotinic acetylcholine receptor (nAChR) subunit were dramatically decreased both in the peripheral and central nervous system. The repeated administration (30 mg/kg/day per os, for 3 weeks) of (R)-ICH3, the most active enantiomer of a novel alpha7 nAChR agonist, and of PNU-282987 prevented the receptor down-regulation. On the other hand, both agonists per se up-regulated the alpha7 nAChR subunit compared to control. (R)-ICH3 and PNU-282987 significantly reduced oxaliplatin-dependent alterations of the pain threshold when noxious or non-noxious stimuli were used. Further ex vivo analysis highlighted their neuroprotective effects in dorsal root ganglia and peripheral nerves. The two agonists did not prevent the increase in microglia cell number induced by oxaliplatin in the central nervous system. Astrocyte density was enhanced by the agonist treatment in the spinal cord, thalamus and somatosensory area 1 as opposed to the effects of oxaliplatin treatment. (R)-ICH3 and PNU 282987 per se increased glial cell number in a region-specific manner. In summary, alpha7 nAChR is involved in oxaliplatin-dependent neuropathology and the agonists (R)-ICH3 and PNU-282987 reduce pain and protect nervous tissue with concomitant glial activation. Since glial cells play a role both in pain and in neuroprotection, an alpha7 AChR-dependent modulation of glial functions is suggested to distinguish rescue signals from the pathological pain-mediating pathway. PMID- 24225198 TI - Cooperation of taurine uptake and dopamine D1 receptor activation facilitates the induction of protein synthesis-dependent late LTP. AB - Co-activation of NMDA and dopamine receptors is required for the induction of the late phase of LTP (L-LTP) that is dependent on new protein synthesis. Other neuromodulatory substances may also contribute to this process. Here, we examined whether taurine is one of the neuromodulators contributing to L-LTP induction, since it is known that taurine uptake induces a long-lasting synaptic potentiation dependent on protein synthesis, and taurine uptake inhibition blocks L-LTP induced by tetanization. Experiments were conducted using rat hippocampal slices where field synaptic potentials were evoked and recorded in CA3-CA1 synapses. Taurine (1 mM) applied 10 min before a high frequency stimulation (HFS) train converted a transitory early-LTP (E-LTP) into an L-LTP dependent on protein synthesis. This taurine effect was blocked by a taurine uptake inhibitor. A facilitation of L-LTP induction was also obtained by pre-application of SKF38393, a D1/D5 dopamine receptor (D1R) agonist. In this case, LTP facilitation was not affected by the taurine uptake inhibitor. Nevertheless, when taurine and SKF38393 were simultaneously pre-applied at a concentration that individually did not modify E-LTP, they produced a synergistic mechanism that facilitated the induction of L-LTP with a sole HFS train. This facilitation of L-LTP was blocked by inhibiting either taurine uptake or D1R activation. Taurine and SKF38393 activated different signaling pathways to transform E-LTP into L-LTP. Taurine induced L-LTP facilitation required MAPK activation, while D1R-agonist-induced facilitation depended mainly on PKA activation and partially on MAPK activation. On the other hand, the synergistic mechanisms induced by the cooperative action of taurine and SKF38393 were impaired by inhibitors against MAPK, PKA and PI3-K. This pharmacological profile resembles that displayed by L-LTP induced by three HFS trains at 10-min intervals. These results indicate that taurine uptake is necessary and cooperates with other neurotransmitter systems in the induction of L-LTP. PMID- 24225199 TI - Predictors, cost, and outcomes of patients with acute coronary syndrome who receive optimal secondary prevention therapy: results from the antiplatelet treatment observational registries (APTOR). AB - BACKGROUND: We sought to evaluate outcomes, costs of care, quality of life and predictors at 12 months in patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and evaluated use of optimal secondary prevention therapy, defined as use of aspirin and clopidogrel along with >= 3 of the following 4 therapies at both hospital discharge and at one-year post-PCI: statins, beta-blockers, ARB/ACE-inhibitors, and exercise or diet. METHODS: Data were from the prospective, observational APTOR study of 14 European countries from 2007 to 2009 (n=4184 patients). RESULTS: Optimal therapy was received in 43% of patients. Use of optimal therapy varied significantly by country. Diet or exercise at 1 year was more likely prescribed to the optimal cohort (34% vs 16%) as was dual antiplatelet therapy (99% vs 49%). Rates of CV event (3.1% vs 3.5%), bleeding (2.9% vs 2.8%) and mortality (0.9% vs 1.3%) at 1 year were similar between the optimal and non-optimal cohorts, respectively. Total costs were similar for both cohorts, but differences in post-discharge costs were observed (optimal: L1760 [L1682-L1844]; non-optimal: L1492 [L1434 L1554]), primarily due to post-discharge medication and resource use. CONCLUSIONS: In conclusion, in this contemporary, European ACS-PCI registry, optimal therapy was low (<50%) overall, particularly for diet or exercise and dual antiplatelet therapy, highlighting a considerable gap between evidence-based guidelines and implementation of such treatments. Whether this gap reflects a missed opportunity to improve patient outcomes or whether it reflects appropriate deviation from guidelines by front-line clinicians requires further investigation. PMID- 24225200 TI - Using a large cuff reduces the difference between peripheral and central blood pressure readings. The BP-CUFF study. PMID- 24225201 TI - Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. AB - BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist, with undefined prognostic and therapeutic implications. We investigated clinical profile and outcomes of patients with chronic HF and COPD, notably the efficacy and safety of ivabradine, a heart rate-reducing agent. METHODS: 6505 ambulatory patients, in sinus rhythm, heart rate >= 70 bpm and stable systolic HF were randomised to placebo or ivabradine (2.5 to 7.5mg bid). Multivariate Cox model analyses were performed to compare the COPD (n=730) and non-COPD subgroups, and the ivabradine and placebo treatment effects. RESULTS: COPD patients were older and had a poorer risk profile. Beta-blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. The primary endpoint (PEP) and its component, hospitalisation for worsening HF, were more frequent in COPD patients (HRs f, 1.22 [p=0.006]; and 1.34 [p<0.001]) respectively, but relative risk was reduced similarly by ivabradine in both COPD (14%, and 17%) and non-COPD (18% and 27%) patients (p interaction=0.82, and 0.53, respectively). Similar effect was noted also for cardiovascular death. Adverse events were more common in COPD patients, but similar in treatment subgroups. Bradycardia occurred more frequently in ivabradine subgroups, with similar incidence in patients with or without COPD. CONCLUSIONS: The association of COPD and HF results in a worse prognosis, and COPD represents a barrier to optimisation of beta-blocker therapy. Ivabradine is similarly effective and safe in chronic HF patients with or without COPD, and can be safely combined with beta blockers in COPD. PMID- 24225202 TI - Metabolic engineering of Escherichia coli to optimize melanin synthesis from glucose. AB - BACKGROUND: Natural aromatic polymers, mainly melanins, have potential and current applications in the cosmetic, pharmaceutical and chemical industries. The biotechnological production of this class of compounds is based on tyrosinase dependent conversion of L-tyrosine and other aromatic substrates into melanins. The purpose of this work was to apply metabolic engineering for generating Escherichia coli strains with the capacity to synthesize an aromatic polymer from a simple carbon source. RESULTS: The strategy was based on the expression in E. coli of the MutmelA gene from Rhizobium etli, encoding an improved mutant tyrosinase. To direct the carbon flow from central metabolism into the common aromatic and the L-tyrosine biosynthetic pathways, feedback inhibition resistant versions of key enzymes were expressed in strains lacking the sugar phosphotransferase system and TyrR repressor. The expressed tyrosinase consumed intracellular L-tyrosine, thus causing growth impairment in the engineered strains. To avoid this issue, a two phase production process was devised, where tyrosinase activity was controlled by the delayed addition of the cofactor Cu. Following this procedure, 3.22 g/L of melanin were produced in 120 h with glucose as carbon source. Analysis of produced melanin by Fourier transform infrared spectroscopy revealed similar characteristics to a pure eumelanin standard. CONCLUSIONS: This is the first report of a process for producing melanin from a simple carbon source at grams level, having the potential for reducing production cost when compared to technologies employing L-tyrosine as raw material. PMID- 24225203 TI - Mitochondrial targeting of alpha-tocopheryl succinate enhances its anti mesothelioma efficacy. AB - Malignant mesothelioma (MM) is a fatal neoplastic disease with no therapeutic option. Therefore, the search for novel therapies is of paramount importance. METHODS: Since mitochondrial targeting of alpha-tocopheryl succinate (alpha-TOS) by its tagging with triphenylphosphonium enhances its cytotoxic effects to cancer cells, we tested its effect on MM cells and experimental mesotheliomas. RESULTS: Mitochondrially targeted vitamin E succinate (MitoVES) was more efficient in killing MM cells than alpha-TOS with IC50 lower by up to two orders of magnitude. Mitochondrial association of MitoVES in MM cells was documented using its fluorescently tagged analogue. MitoVES caused apoptosis in MM cells by mitochondrial destabilization, resulting in the loss of mitochondrial membrane potential, generation of reactive oxygen species, and destabilization of respiratory supercomplexes. The role of the mitochondrial complex II in the activity of MitoVES was confirmed by the finding that MM cells with suppressed succinate quinone reductase were resistant to MitoVES. MitoVES suppressed mesothelioma growth in nude mice with high efficacy. DISCUSSION: MitoVES is more efficient in killing MM cells and suppressing experimental mesotheliomas compared with the non-targeted alpha-TOS, giving it a potential clinical benefit. PMID- 24225204 TI - Italian registry of cardiac magnetic resonance. AB - OBJECTIVES: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). MATERIALS AND METHODS: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 +/- 19 years; range 1-92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. RESULTS: Exams were performed with 1.5T scanners in 96% of cases followed by 3T (3%) and 1T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. CONCLUSIONS: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile. PMID- 24225205 TI - Medication management for people with dementia in primary care: description of implementation in the DelpHi study. AB - BACKGROUND: As the population ages, the relative and absolute number of age associated diseases such as dementia will increase. Evaluation of the suitability and intake of medication and pharmacological treatment is an important aspect of care for people with dementia, especially if they live at home. Regular medication reviews and systematic cooperation between physicians and pharmacists are not common in routine care. Medication management (MM), based on such a comprehensive home medication review could help to reduce drug-related problems and costs. The present article presents a medication management specifically for the application in the ambulatory setting and describes its implementation as part of a larger trial. METHODS/DESIGN: A home medication review (HMR) and MM is implemented as part of the DelpHi study, a population based prospective, cluster randomized controlled intervention study to test the efficacy and efficiency of the implementation of a collaborative care model in primary care. PARTICIPANTS: people with dementia (PWD) and their caregivers are recruited by the patient's general practitioner. Inclusion criteria are a positive screening result for dementia, living at home and regular intake of drugs. PWD are asked to specify their regular pharmacy which is asked to participate in the study, too. INTERVENTION: a comprehensive HMR is conducted as computer-assisted personal interview by specifically qualified Dementia Care Manager (DCM) at the people's home. It includes detailed information about drugs taken, their storage, administration, adherence and adverse events. The MM is conducted in cooperation between DCM, pharmacist and general practitioner and consists of a pharmaceutical evaluation, pharmaceutical recommendations and their application. Pharmacists are trained and provided with regularly updated information. The MM is designed to give information and recommendations concerning antidementia drugs, occurrence of drug related problems, intake of anticholinergic drugs, potentially clinically relevant drug-drug-interactions, adverse drug events and medication adherence. DISCUSSION: The DelpHi-approach for medication management employs comprehensive instruments and procedures in the primary care setting under routine care conditions, and this approach should be useful in improving pharmacotherapy as part of the comprehensive treatment and care for people with dementia. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, number NCT01401582. PMID- 24225207 TI - [High-quality cardiopulmonary resuscitation: exploration and challenges]. PMID- 24225206 TI - Adjuvant radiotherapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials. AB - BACKGROUND: Radiotherapy (RT) improves overall survival (OS) of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved lymph nodes (LN). The contribution of RT to the regional LN to this survival benefit was poorly understood. Recently, the results of three large randomized trials addressing this question have become available. MATERIAL AND METHODS: The published abstracts (full publication pending) of the MA.20 (n=1832) and the EORTC 22922-10925 (EORTC) (n=4004) trial and the full publication of the French trial (n=1334) were basis of the meta-analysis. Main eligibility criteria were positive axillary LN (all trials), LN negative disease with high risk for recurrence (MA.20), and medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial tested the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS). RESULTS: Regional RT of the MS-LN and the IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS (Hazard Ratio (HR) 0.85 (95% CL 0.75 - 0.96)). Adding the results of the French trial and using the random effects model to respect the different design of the French trial, the effect on OS of regional radiotherapy was still significant (HR 0.88 (95% CL 0.80 - 0.97)). The absolute benefits in OS were 1.6% in the MA.20 trial at 5 years, 1.6% in the EORTC trial at 10 years, and 3.3% in the French trial at 10 years (not significant in single trials). Regional radiotherapy of the MS-LN and the IM-LN (MA.20 and EORTC) was associated with a significant improvement of DFS (HR 0.85 (95% CL 0.77 - 0.94)) and DMFS (HR 0.82 (95% CL 0.73 - 0.92)). The effect sizes were not significantly different between trials for any end point. CONCLUSION: Additional regional radiotherapy to the internal mammary and medial supraclavicular lymph nodes statistically significantly improves DFS, DMFS, and overall survival in stage I-III breast cancer. PMID- 24225208 TI - [Effects of tramadol hydrochloride preconditioning on the activation of nuclear factor-KappaB induced by norepinephrine in cultured neonatal rat cardiomyocytes]. AB - OBJECTIVE: To investigate the effects of tramadol hydrochloride preconditioning on activation of nuclear factor-KappaB (NF-KappaB) induced by norepinephrine (NE) in cultured neonatal rat cardiomyocytes. METHODS: 1 to 3-day old Sprague-Dawley (SD) rats were raised, and their cardiomyocytes were cultured for 4 to 5 days. Sixteen wells of cultured cardiomyocytes were randomly divided into four groups (n=4): blank control group, NE1 group in which the cells were incubated with 1*10(-6) mmol/L of NE, NE2 group in which cells were incubated with 1*10(-7) mmol/L of NE, and NE3 group in which cells were incubated with 1*10(-8) mmol/L of NE. Another 12 wells of cultured cardiomyocytes were randomly divided into three groups (n=4): blank control group, NE3 group in which cells were incubated with 1*10(-8) mmol/L of NE, tramadol plus NE group (T + NE group) in which cells were incubated with 1*10(-5) mmol/L of tramadol hydrochloride plus 1*10(-8) mmol/L of NE. Tramadol hydrochloride was added 30 minutes before the use of NE in T + NE group. After exposure to NE for 24 hours, the expression and activation of NF KappaB in the cultured cardiomyocytes were determined by immunocytochemistry and flow cytometry (FCM). RESULTS: The results of immunocytochemistry showed that the expression of NF-KappaB (including average optical density and positive units) in NE3 group was significantly increased as compared with that in the blank control group (A average optical density: 0.30+/-0.03 vs. 0.12+/-0.04, t=7.200, P=0.008; positive units: 39+/-14 vs. 22+/-6, t=4.610, P=0.020). The results of FCM showed that the levels of cytoplasm NF-KappaB in cultured cardiomyocytes were decreased significantly in NE1 group, NE2 group and NE3 group compared with blank control group [(45.8+/-1.9)%, (38.3+/-1.8)%, (20.9+/-1.6)% vs. (54.6+/-0.6)%, all P<0.05], and the level in NE3 group was significantly lower than that in NE1 and NE2 groups (both P<0.05). The level of the cardiomyocytes cytoplasm NF-KappaB in T + NE group was higher than that in NE3 group [(57.8+/-0.4)% vs. (20.9+/-1.6)%, t=57.524, P=0.001]. CONCLUSIONS: Tramadol hydrochloride preconditioning can inhibit the activation of NF-KappaB induced by NE in cultured rat cardiomyocytes. It plays a protective role in ischemia myocardium at cell level. PMID- 24225209 TI - [The value of D-dimer for etiological diagnosis of mortal chest pain: an analysis of 438 cases]. AB - OBJECTIVE: To investigate the role of plasma D-dimer in differentiating fatal chest pain due either to acute myocardial infarction (AMI), acute pulmonary embolism (APE) or acute aortic dissection (AAD) in emergency department. METHODS: The data of a total of 445 consecutive patients complaining chest (back) pain and/or dyspnea who visited emergency department of Peking University Third Hospital from January 2011 to January 2012 were retrospectively analyzed. All cases were either diagnosed as AMI, APE or AAD finally. D-dimer concentrations were assessed and compared among different groups. The receiver operating characteristic curve (ROC curve) was established. The potency of D-dimer in distinguishing AMI, non-ST-segment elevation myocardial infarction (NSTEMI) by difference in values was assessed. RESULTS: Finally, 438 cases were enrolled, including 327 AMI [253 ST-segment elevation myocardial infarction (STEMI) and 74 NSTEMI], 76 APE and 35 AAD cases. The D-dimer concentrations in AMI group [0.21(0.15, 0.33) mg/L] were significantly lower than those in APE group [1.06 (0.86, 3.01) mg/L, Z=-11.416, P<0.001], AAD group [1.79 (0.83, 3.37) mg/L, Z= 8.715, P<0.001], APE/AAD group [1.15 (0.85, 3.13) mg/L, Z=-13.509, P<0.001]. The D-dimer concentrations in STEMI group were significantly lower than those in NSTEMI group [mg/L: 0.20 (0.15, 0.30) vs. 0.24 (0.17, 0.54), Z=-3.248, P=0.001]. The area under ROC curve (AUC) to discriminate AMI from APE/AAD was 0.929+/ 0.015, and optimal value was 0.535 mg/L. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) with cut-off value of 0.535 mg/L were 86.2%, 93.7%, 97.6%, 69.8%,13.68, 0.15, while sensitivity, specificity, PPV, NPV, PLR, NLR with cut-off value of 0.5 mg/L were 84.4%, 93.7%, 97.5%, 67.1%, 13.40, 0.17. The AUC to discriminate NSTEMI from APE/AAD was 0.881+/-0.028. Sensitivity, specificity, PPV, NPV with cut-off value of 0.535 mg/L were 75.7%, 93.7%, 88.9%, 85.2%, while sensitivity, specificity, PPV, NPV with cut-off value of 0.5 mg/L were 70.3%, 93.7%, 88.1%, 82.5%, respectively. CONCLUSIONS: D-dimer is a better index in differentiating AMI from APE/AAD in emergency setting, guiding further examination and therapy, and increasing diagnosis efficiency. PMID- 24225210 TI - [Comparison of value of GRACE, APACHEII and REMS for early prognosis of death in patients with acute myocardial infarction]. AB - OBJECTIVE: To evaluate and compare the predictive value of short-term risk of death of global registry of acute coronary events (GRACE) risk scores, acute physiology and chronic health evaluation II (APACHEII) scores and rapid emergency medicine score (REMS) in patients with acute myocardial infarction (AMI). METHODS: A retrospective review of clinical data of 390 patients with AMI admitted from October 2012 to March 2013 in emergency department and cardiology care unit (CCU) in Guizhou People's Hospital were performed. The lowest scores within 24 hours of GRACE risk score, APACHEII risk score, and REMS risk score, respectively, for each patient were recorded. Mortality rate within 30 days after onset was calculated. Prediction of the mortality rate of AMI within 30 days as made in three scoring systems was compared. RESULTS: A total of 54 patients died from cardiovascular disease within 30 days. GRACE risk scores, APACHEII scores, and REMS risk scores were higher in non-survivors as compared with that of survivors (GRACE: 206.09+/-24.67 vs. 150.17+/-25.72, t=-4.349, P=0.000; APACHEII: 15.81+/-7.60 vs. 7.50+/-2.83, t=-4.182, P=0.000; REMS: 7.11+/-2.70 vs. 5.38+/ 2.59, t=-2.345, P=0.020). Area under the receiver operator characteristic curve (ROC curve) for GRACE risk scores, APACHEII risk scores and REMS in patients with AMI died from cardiac vascular disease in 30 days were 0.862 [95% confidence interval (95%CI) 0.76-0.95, P=0.000], 0.825 (95%CI 0.71-0.93, P=0.002) and 0.615 (95%CI 0.46-0.77, P=0.192), sensitivity of three kinds of scoring system was 92.32%, 76.91%, 69.26%, respectively, with specificity of 66.23%, 77.84%, 54.02% respectively. CONCLUSIONS: GRACE and APACHEII scores for patients with AMI risk of short-term death showed more accurate in predicting early than GRACE scores, and REMS for AMI risk of short-term death did not have predictive value. PMID- 24225211 TI - [Experimental study of the effect of Shenmai injection on post-cardiac arrest syndrome in rabbit]. AB - OBJECTIVE: To observe the effects of Shenmai injection on post-cardiac arrest syndrome (PCAS) in rabbit and to discuss the underlying mechanism. METHODS: Seventy-three rabbits were divided into sham operation group (n=10), model group (n=21), high and low dosage Shenmai group (each n=21) by random number table method. The animal model of cardiac arrest was reproduced by clamping the endotracheal tube. The rabbits in sham operation group were only given anesthesia and tracheostomy without producing asphyxia by clamping the trachea to produce asphyxia. Serum creatine kinase isoenzyme (CK-MB), alanine aminotransferase (ALT), creatinine (Cr), troponin I (cTnI), tumor necrosis factor-alpha (TNF alpha), interleukin (IL-1beta, IL-6) and nuclear transcription factors-KappaB (NF KappaB) levels were determined before asphyxia and 3, 6, 12, 24, 48 hours after restoration of spontaneous circulation (ROSC), and dynamic changes in various parameters were determined in each group. RESULTS: All the indexes in model group and Shenmai groups were gradually increased after ROSC. IL-6 peaked at 6 hours, IL-1beta peaked at 12 hours, CK-MB, cTnI, TNF-alpha and NF-KappaB peaked at 24 hours, ALT and Cr peaked at 48 hours. CK-MB, ALT, cTnI levels in high dosage Shenmai group were significantly lower than those in the model group 6 hours after ROSC [CK-MB (U/L): 571.69+/-24.39 vs. 587.98+/-22.38, ALT (U/L): 74.88+/ 8.71 vs. 81.49+/-5.79, cTnI (MUg/L): 7.82+/-1.52 vs. 8.97+/-1.87], serum levels of TNF-alpha and NF-KappaB 12 hours after ROSC [TNF-alpha(ng/L): 120.36+/-12.38 vs. 135.23+/-20.13, NF-KappaB (ng/L): 2.18+/-0.17 vs. 2.29+/-0.15], and the serum levels of IL-1beta and IL-6 24 hours after ROSC in high dose Shenmai group were significantly lower than those in the model group [IL-1beta (ng/L): 1.49+/-0.13 vs. 1.62+/-0.17, IL-6 (ng/L): 72.01+/-5.02 vs. 79.35+/-11.28], however, serum Cr in high dosage Shenmai group was significantly lower than in the model group at 24 hours after ROSC (MUmol/L: 158.73+/-4.40 vs. 162.97+/-5.02, P<0.05 or P<0.01). In low dosage Shenmai group, the serum level of CK-MB, Cr, cTnI were significantly lower than those in the model group 24 hours after ROSC [CK-MB (U/L): 1 769.00+/-19.73 vs. 2 120.96+/-24.15, Cr (MUmol/L): 159.32+/-3.02 vs. 162.97+/-5.02, cTnI (MUg/L): 12.17+/-3.04 vs. 14.89+/-3.09,P<0.05 or P<0.01). But after ROSC, ALT, TNF-alpha, IL-1beta, IL-6 and NF-KappaB showed no significant change as compared with model group. In high dosage Shenmai group, serum levels of CK-MB and cTnI at 6, 12 hours and TNF-alpha and IL-6 at 24 hours after ROSC were significantly lower than those in the low dosage Shenmai group(all P<0.05). CONCLUSIONS: Severity of injury of different organs in rabbit cardiac arrest model showed positive correlation with the alterations in serum TNF-alpha, IL 1beta, IL-6, NF-KappaB after cardiopulmonary resuscitation. Early use of Shenmai injection after cardiopulmonary resuscitation can retard the development of PCAS, especially in the protection of ischemia and hypoxia of myocardium after cardiopulmonary resuscitation. PMID- 24225212 TI - [The clinical value of atrial natriuretic peptide in early diagnosis of sepsis]. AB - OBJECTIVE: To evaluate the clinical value and specificity of atrial natriuretic peptide (ANP) in early diagnosis of sepsis. METHODS: A prospective study was performed. Data of patients with sepsis were consecutively collected from September 2007 to December 2012 according to the international criteria for the diagnosis of sepsis, and that of 114 patients admitted to intensive care unit (ICU) and the cadre health care ward were divided into three groups: systemic inflammatory response syndrome (SIRS) group (n=37), sepsis group (n=41) and severe sepsis group (including severe sepsis and septic shock, n=36). Venous blood of each patient was drawn instantly when admitted to ICU. The concentration of plasma ANP in each group was determined on the 1st day using a new type of sandwich immunofluorescence assay, and other biomarkers, such as procalcitonin (PCT, detected with double antibody immunochemi luminometry), blood lactic acid (detected with electrode meter), and C-reactive protein (CRP, detected with immunonephelometric analysis), and the acute physiology and chronic health evaluation II (APACHEII) score was recorded. APACHEII score and biomarkers were compared among three groups. The risk factor for severity was confirmed with stepwise regression, and the value of each index in early diagnosis of sepsis was analyzed with receiver operating characteristic (ROC) curve. RESULTS: The plasma concentration of ANP exhibited a gradual increase with the aggravation of the disease, and the median ANP value was found to be highest in the severe sepsis group compared with SIRS group and sepsis group [MUg/L: 0.26 (0.22) vs. 0.19 (0.05), 0.21 (0.08), P<0.01 and P<0.05]. The regression equation was established at y=0.69 + 0.66APACHEIIscore + 1.285 ANP value, with group as independent variable, and APACHEII score, ANP, PCT, CRP and blood lactic acid value as dependent variables. It could be concluded that APACHEII score and ANP value were correlated with severity of sepsis, and accordingly they were regarded as the independent predictors of severity of sepsis. It was found through the ROC curve analysis of ANP in the sepsis patients, that the area under the ROC curve for ANP [0.805, P=0.000, 95% confidence interval (95%CI) 0.726-0.883, sensitivity 75.8%, specificity 78.4%] was similar with the area under the APACHEII score (0.820, P=0.000, 95%CI 0.742-0.897, sensitivity 68.4%, specificity 78.4%), and it was apparently higher than AUCs of PCT (0.716, P=0.000, 95%CI 0.622-0.810, sensitivity 67.1%, specificity 62.2%), CRP (0.569, P=0.236, 95%CI 0.463-0.675, sensitivity 76.3%, specificity 41.5%), or blood lactic acid (0.566, P=0.254, 95%CI 0.453-0.679, sensitivity 75.0%, specificity 48.6%). CONCLUSIONS: Plasma ANP concentration is clinically valuable in early diagnosis and severity assessment of sepsis, and it is more specific and sensitive than biomarkers PCT and CRP. PMID- 24225213 TI - [A study of relationship between dialectical classification according to traditional Chinese medicine of acute coronary syndrome with serum osteoprotegerin and its ligand]. AB - OBJECTIVE: To investigate the relationship between osteoprotegerin (OPG) system and acute coronary syndrome (ACS) and its classification according to traditional Chinese medicine (TCM). METHODS: A prospective study was conducted. The patients with ACS (n=210) and the patients with stable angina pectoris (SAP, n=200) were enrolled. The serum OPG and its ligand (sRANKL) were determined by enzyme-linked immunosorbent assay (ELISA), the OPG/sRANKL ratio was calculated, and the number of coronary vessels was involved, finally their relationship with the typing according to TCM was evaluated. One hundred and fifty non-coronary heart disease patients were enrolled as control. RESULTS: The serum OPG, OPG/sRANKL in ACS and SAP groups were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). The OPG, OPG/sRANKL in ACS groups were significantly higher than those in SAP group (both P<0.01). Serum OPG, OPG/sRANKL in ACS patients with different number of coronary vessel disease were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). OPG and OPG/sRANKL were gradually increased with increase in number of diseased coronary vessels, but the sRANKL descended (P<0.05 or P<0.01). Serum OPG and OPG/sRANKL were descended according to dialectical classification of TCM: Yang Qi weakening syndrome>Qi and blood stagnation syndrome>Qi deficiency with blood stasis syndrome>stagnation of phlegm blocks the heart-vessels syndrome>Yin deficiencies of the heart and the kidney syndrome>deficiency of both Qi and Yin syndrome, among them they were significantly higher in Yang Qi failure syndrome and Qi and blood stagnation syndromes than those of both Qi and Yin syndrome [OPG(ng/L): 621.38+/-32.86, 617.63+/-39.60 vs. 593.86+/-36.19, OPG/sRANKL(g/mol): 1 018.98+/ 106.03, 1 011.27+/-121.61 vs. 942.16+/-115.82, P<0.05 or P<0.01]. Among different types of TCM in ACS group the serum sRANKL was significantly lower than that in control group (all P<0.01), but the difference among different types was not significant. CONCLUSIONS: Serum OPG, sRANKL, OPG/sRANK levels were related with incidence and severity of coronary lesions in ACS patients. Serum OPG and OPG/sRANKL ratio may have correlation with Yang Qi weakening syndrome and Qi deficiency with blood stasis syndrome. PMID- 24225215 TI - [Analysis of drug resistance of Acinetobacter baumannii and its related factors in ICU]. AB - OBJECTIVE: To investigate drug resistance of Acinetobacter baumannii and its related factors in intensive care unit (ICU), and to provide clinical basis for prevention and treatment. METHODS: A retrospective analysis was conducted. Clinical data was collected from 1 050 patients in ICU of Foshan Hospital of Traditional Chinese Medicine from January 2011 to June 2013. The risk factors of nosocomial infection were analyzed with univariate analysis. The independent risk factor was sieved from the risk factors with P<0.05 with unconditional logistic regression analysis to analyze the related factors and drug resistance of Acinetobacter baumannii in ICU. RESULTS: One hundred and thirteen patients suffering from nosocomial infection of Acinetobacter baumannii were found, and its incidence rate was 10.76%. There were 96 cases of infection of multi-drug resistant, extensive-drug resistant and pan-drug resistant Acinetobacter baumannii, accounting for 84.96%. Acinetobacter baumannii detection rate was 79.65% in sputum, 10.62% in urine, 4.42% in wound secretion, 3.54% in blood, and 1.77% in other drainage discharges, respectively. Univariate analysis showed that mechanical ventilation, ICU stay time>=7 days, coma [Glasgow coma score (GCS)<8], usage of broad-spectrum antibiotics were risk factors of nosocomial infection of Acinetobacter baumannii. Multivariate logistic analysis showed that the independent risk factors of nosocomial infection caused by Acinetobacter baumannii in ICU were mechanical ventilation [odds ratio (OR)= 2.957, 95%confidence interval (95%CI) 1.106-6.253, P=0.023], ICU stay time>=7 days (OR=2.991, 95%CI 1.135-6.544, P=0.022), coma (GCS<8,OR=2.894, 95%CI 1.803-7.462, P=0.010), and usage of broad-spectrum antibiotics (OR=3.054, 95%CI 1.009-6.550, P=0.004). Rate of resistance to polymyxin B was the lowest (6.19%), and it was followed by tobramycin and tigecycline, 11.50% and 28.32%, respectively. CONCLUSIONS: Acinetobacter baumannii in ICU was conditional pathogenic bacteria with high infection rate, and the lower respiratory tract was the main site of infestation. The related factors include mechanical ventilation, ICU stay time, coma, usage of broad-spectrum antibiotics. Its antimicrobial resistance rate was high. Comprehensive measures, including environmental isolation, strict bed unit disinfection, enforcement of hand disinfection, strengthening the effort to shorten the duration of mechanical ventilation, reduction of ICU length of stay, enhancement of drainage of mucus, excretions, and other body fluids, and rational use of antibiotics should be encouraged in order to reduce Acinetobacter baumannii in ICU. PMID- 24225214 TI - [An investigation on correlation of severity of brain injury with the expression of activin A and C-reactive protein]. AB - OBJECTIVE: To determine the dynamic change in serum levels of activin A (ACTA) and C-reaction protein (CRP) in patients with brain injury, and to investigate its significance. METHODS: A prospective study was conducted. A total of 57 adult patients with brain injury occurring within 24 hours admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from August 2012 to June 2013 were enrolled. The patients were allocated into three groups according to their Glasgow coma scale (GCS) as follows: minor brain injury (GCS 13-15, n=17), moderate brain injury (GCS 9-12, n=18), heavy brain injury (GCS 3 8, n=22). The clinical and related laboratory data (reflecting the function of liver, kidney, lung, blood coagulability etc.) were recorded after ICU admission. At the same time, venous samples were collected on the day 1, 2, 3, 5, 7 after ICU admission for determination of ACTA with enzyme linked immunosorbent assay (ELISA) and CRP with fluorescence immunoassay technology. The correlation between ACTA and CRP was analyzed by linear correlation. The receiver operating characteristic (ROC) curve was plotted to analyze the accuracy of ACTA and CRP as a prognostic indicator in brain injury. Fifteen healthy persons were enrolled as the control group. RESULTS: The serum levels of ACTA and CRP in patients with minor, moderate and heavy brain injury were significantly higher than those in healthy control group [ACTA (MUg/L): 23.96+/-3.55, 42.06+/-5.67, 52.32+/-4.46 vs. 13.66+/-2.45, all P<0.01; CRP (mg/L): 14.12+/-2.45, 23.05+/-2.85, 30.93+/-2.35 vs. 3.42+/-2.25, all P<0.01]. As the patients' condition worsening, levels of ACTA and CRP tended to elevate (all P<0.01). Levels of ACTA and CRP in minor, moderate and heavy brain injury groups were increased after ICU admission. On day 3, levels of serum ACTA and CRP reached the peak values [ACTA (MUg/L):30.62+/ 2.54, 51.35+/-2.55, 60.52+/-2.55; CRP (mg/L): 18.62+/-2.64, 30.35+/-2.25, 37.52+/ 2.55], and then they lowered gradually. In minor and moderate brain injury groups, the levels of ACTA and CRP were slowly descending, and on day 7, they maintained at a lower level [ACTA (MUg/L): 13.68+/-2.54, 37.74+/-2.55; CRP (mg/L): 6.68+/-2.44, 19.74+/-2.55]. On the contrary, the levels of ACTA and CRP in heavy brain injury group persistently maintained at a high level on day 7 [ACTA: (42.32+/-2.54) MUg/L, CRP: (33.32+/-2.56) mg/L]. There were significant differences in ACTA and CRP among different degrees of brain injury groups (all P<0.01). There was a positive correlation between ACTA and CRP (r=0.958, P=0.007). ROC curve analysis showed that the sensitivity for brain injury prediction was 93.3% for ACTA with specificity 95.0%, area under ROC curve(AUC) 0.843, and the sensitivity for CRP was 89.1% with specificity 68.2%, AUC 0.723. CONCLUSIONS: Serum levels of ACTA and CRP in patients with brain injury are strongly correlated with the severity of the injury. Furthermore, ACTA is more sensitive than CRP in detecting early brain injury. Therefore, ACTA is a specific factor for detecting brain injury. PMID- 24225216 TI - [Clinical significance of dynamic monitoring of procalcitonin in guiding the use of antibiotics in patients with sepsis in ICU]. AB - OBJECTIVE: To investigate the significance of dynamic monitoring of procalcitonin (PCT) in guiding the use of antibiotics for treating patients with sepsis in intensive care unit (ICU). METHODS: Eighty-two patients with sepsis from January 2012 to June 2013 hospitalized in ICU of First Hospital of Jilin University were enrolled, and they were randomly divided into regular antibiotic therapy group (RAT group, n=40) and PCT monitoring in guiding the use of antibiotics group (PCT group, n=42). Patients in RAT group were treated according to principle of antibiotics usage, while in PCT group patients' PCT value was observed everyday. When no active symptoms of infection were shown, and acute physiology and chronic health evaluation II (APACHEII) scores declined, PCT value decreased over 90% or PCT value lower than 0.25 MUg/L time point were selected as drug withdrawal indication. The general status of the patient, antimicrobial drug use time, and prognosis were compared between the two groups, and Kaplan-Meier method was used for survival curve analysis. Variance analysis was used for repeating measurement to observe dynamic serum PCT level of the two groups of patients for survival and death during 7 days. RESULTS: Mann-Whitney U test or chi(2) test showed that there were no statistical significance in age, gender, APACHEII score, blood culture positive rate, sputum culture positive rate, cardiac insufficiency, renal failure, respiratory failure, and ventilator and hemofiltration usage (all P>0.05). Log Rank test results showed that the time of antimicrobial drug usage was significantly reduced in PCT group than that in RAT group [days: 8.1+/-0.3, 95% confidence interval (95%CI 8.3-9.7) vs. 9.3+/-0.3 (95%CI 8.7-10.1), P=0.013]. Kaplan-Meier univariate survival curves showed that the speed of curve declination in PCT group was faster significantly than that in RAT group, suggesting that the time of using antimicrobial drug was shortened. There was no significant difference in length of hospital stay, ICU stay time, number of death in 28 days, number of cases of recurrence in 28 days and clinical cure rate between two groups (all P>0.05). PCT level in non-survivors in both groups was significantly higher than that in the survivors, exceeding more than 10 MUg/L in the early and late stages of treatment. CONCLUSIONS: Dynamic monitoring of PCT can effectively reduce antimicrobial drug use in ICU patients with sepsis, but there is no significant difference in patients' prognosis. PMID- 24225217 TI - [An analysis of relationship between the severity of coronary artery lesion and risk factors of cardiovascular events in Tianjin]. AB - OBJECTIVE: to evaluate the correlation between the severity of coronary artery lesion and multiple risk factors of events of coronary heart disease (CHD) in patients with coronary arteriography (CAG) in Tianjin. METHODS: A retrospective study was conducted. One thousand six hundred and twenty-nine patients with CHD as diagnosed with CAG in Tianjin Chest Hospital were enrolled in the study. Using the SYNTAX score to evaluate the outcomes of CAG, The patients wer divided into three groups, i.e. low (0-22, n=962), medium (23-32, n=446) and high (>= 33, n=221) score groups. The relationship between the severity of CHD patients analysis. RESULTS: The single factor analysis results showed that the severer the coronary artery lesion, the higher the SYNTAX score, the higher the proportion of patients having one of single risk factors (old, male, smoking, hypertension, type 2 diabetes mellitus, blood lipid abnormality), the lower the high density lipoprotein cholesterol (HDL-C), and the higher the low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) level, fibrinogen (FIB) content, and body mass index (BMI, all P<0.01). The logistic regression analysis showed that male, old age, hypertension, typed 2 diabetes mellitus, TC were the independent risk factors in aggravating the severity of CHD. Hypertension [ odds ration (OR)=3.947, 95% confidence interval (95% CL) 1.45-10.704, P<0.001] and type 2 diabetes mellitus (OR=5.760, 95% CI 2.549-13.018, P<0.001) were the two most prominent predictors for CHD, while HDL-C was the protective factor for CHD (OR=0.541, 95% CI 0.295-0.992, P=0.992, P=0.004). CONCLUSION. The severity of CHD was closely related to CHD was closely related to various risk factors, among them hypertension and type 2 diabetes mellitus were the most predominant risk factors of CHD. Therefore it should be emphasized that clinicians should control blood pressure, blood glucose, and also blood lipid level in CHD patients to prevent cardiac event. PMID- 24225218 TI - Cordycepin-mediated transcriptional regulation of human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N-BE(2)-C cells. AB - In the present study, we firstly found that cordycepin elevated the gene expression of the human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N BE(2)-C cells. To elucidate the mechanism underlying the upregulation of hST8Sia I gene expression in cordycepin-treated SK-N-BE(2)-C cells, functional characterization of the promoter region of the hST8Sia I gene was performed. Analysis of promoter activity using varying lengths of 5'-flanking region showed a dramatic increase by cordycepin in the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1, and NF kappaB. Site-directed mutagenesis for these binding sites and chromatin immunoprecipitation assay revealed that the NF-kappaB binding site at -731 to 722 is essential for the cordycepin-induced expression of the hST8Sia I in SK-N BE(2)-C cells. Moreover, the hST8Sia I expression induced by cordycepin was significantly repressed by pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB. These results suggested that cordycepin induces upregulation of hST8Sia I gene expression through NF-kappaB activation in SK-N-BE(2)-C cells. PMID- 24225219 TI - The fate of the embedded virgin sand flea Tunga penetrans: hypothesis, self experimentation and photographic sequence. AB - We describe the morphological development of a single penetrated female sand flea (Tunga penetrans) in a medical expatriate working in Madagascar. The embedded parasite developed abnormally in two aspects. First, it lived twice as long as usually. Second, it did not expel a single egg during a period of two months. We explain these abnormalities by the fact that the female sand flea remained virgin after the penetration into the skin and, therefore, mature eggs did not develop. Our observations are seminal findings in a long dispute between entomologists and suggest that normally the fertilization of a female sand flea takes place on-host when it is already embedded in the epidermis. We conclude that a single sand flea lesion in a traveller may develop in a different way as compared to parasites penetrating into the skin of inhabitants living in endemic areas. PMID- 24225220 TI - Patient comfort during treatment with heated humidified high flow nasal cannulae versus nasal continuous positive airway pressure: a randomised cross-over trial. AB - OBJECTIVE: To compare patient comfort in preterm infants treated with heated humidified high flow nasal cannulae (HHHFNC) versus nasal continuous positive airway pressure (NCPAP). DESIGN: Randomised cross-over trial (2*24 h). SETTING: Single tertiary neonatal unit. PATIENTS: 20 infants less than 34 weeks postmenstrual age treated with NCPAP due to mild respiratory illness. INTERVENTIONS: After parental consent, infants were randomised to 24 h of treatment with NCPAP or HHHFNC followed by 24 h of the alternate therapy. MAIN OUTCOME MEASURES: Primary outcome was patient comfort assessed by the EDIN (neonatal pain and discomfort) scale. Secondary outcomes were respiratory parameters (respiratory rate, FiO2, SpO2, TcPCO2), ambient noise, salivary cortisol and parental assessments of their child. RESULTS: We found no differences between HHHFNC and NCPAP in mean cumulative EDIN score (10.7 vs 11.1, p=0.25) or ambient noise (70 vs 74 dBa, p=0.18). Parents assessed HHHFNC treatment as significantly better in the three domains, 1) child satisfied, 2) parental contact and interaction and 3) possibility to take part in care. Mean respiratory rate over 24 h was lower during HHHFNC than CPAP (41 vs 46, p=0.001). Other respiratory parameters were similar. CONCLUSIONS: Using EDIN scale, we found no difference in patient comfort with HHHFNC versus NCPAP. However, parents preferred HHHFNC, and during HHHFNC respiratory rate was lower than during NCPAP. CLINICALTRIALSGOV, NUMBER: NCT01526226. PMID- 24225221 TI - Rapidly involuting congenital haemangioma. PMID- 24225222 TI - Genome wide analysis reveals single nucleotide polymorphisms associated with fatness and putative novel copy number variants in three pig breeds. AB - BACKGROUND: Obesity, excess fat tissue in the body, can underlie a variety of medical complaints including heart disease, stroke and cancer. The pig is an excellent model organism for the study of various human disorders, including obesity, as well as being the foremost agricultural species. In order to identify genetic variants associated with fatness, we used a selective genomic approach sampling DNA from animals at the extreme ends of the fat and lean spectrum using estimated breeding values derived from a total population size of over 70,000 animals. DNA from 3 breeds (Sire Line Large White, Duroc and a white Pietrain composite line (Titan)) was used to interrogate the Illumina Porcine SNP60 Genotyping Beadchip in order to identify significant associations in terms of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). RESULTS: By sampling animals at each end of the fat/lean EBV (estimate breeding value) spectrum the whole population could be assessed using less than 300 animals, without losing statistical power. Indeed, several significant SNPs (at the 5% genome wide significance level) were discovered, 4 of these linked to genes with ontologies that had previously been correlated with fatness (NTS, FABP6, SST and NR3C2). Quantitative analysis of the data identified putative CNV regions containing genes whose ontology suggested fatness related functions (MCHR1, PPARalpha, SLC5A1 and SLC5A4). CONCLUSIONS: Selective genotyping of EBVs at either end of the phenotypic spectrum proved to be a cost effective means of identifying SNPs and CNVs associated with fatness and with estimated major effects in a large population of animals. PMID- 24225223 TI - Effects of selenoprotein S on oxidative injury in human endothelial cells. AB - BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Calpha (PKCalpha) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCalpha were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCalpha gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCalpha. PMID- 24225224 TI - Involvement of a novel genistein-inducible multidrug efflux pump of Bradyrhizobium japonicum early in the interaction with Glycine max (L.) Merr. AB - The early molecular dialogue between soybean and the bacterium Bradyrhizobium japonicum is crucial for triggering their symbiotic interaction. Here we found a single large genomic locus that is widely separated from the symbiosis island and was conspicuously induced within minutes after the addition of genistein. This locus (named BjG30) contains genes for the multidrug efflux pump, TetR family transcriptional regulator, and polyhydroxybutyrate (PHB) metabolism. The induction of BjG30 by genistein was competitively inhibited by daidzein, although both genistein and daidzein are soybean-derived inducers of nodulation (nod) genes. Such a differential expression pattern is also observed in some legume derived flavonoids, which structurally differ in the hydroxy/deoxy group at the 5 position. In addition, not only did the induction start far in advance of nodW and nodD1 after the addition of genistein, but the levels showed distinct concentration dependence, indicating that the induction pattern of BjG30 is completely different from that of nod genes. The deletion of genes encoding either the multidrug efflux pump or PHB metabolism, especially the former, resulted in defective nodulation performance and nitrogen-fixing capability. Taken together, these results indicate that BjG30, and especially its multidrug efflux pump, may play a key role in the early stage of symbiosis by balancing the dual functions of genistein as both a nod gene inducer and toxicant. PMID- 24225227 TI - A facile approach for dual-responsive prodrug nanogels based on dendritic polyglycerols with minimal leaching. AB - A novel pH and redox dual-responsive prodrug nanogel was prepared by an inverse nanoprecipitation method, which is mild and surfactant free, and based on a thiol disulfide exchange reaction and thiol-Michael addition reaction. Highly biocompatible hyperbranched polyglycerol (hPG) was cross-linked with disulfide bonds, to obtain biodegradable nanogels, which could be degraded under intracellular reductive conditions. Doxorubicin (DOX) was conjugated to the biodegradable nanogel matrix via an acid-labile hydrazone linker. This is the first dual-responsive prodrug nanogel system that shows very low unspecific drug leaching, but efficient intracellular release of the payload triggered by the intracellular conditions. Two different prodrug nanogels were prepared with a size of approximately 150nm, which is big enough to take the advantage of the enhanced permeation and retention (EPR) effect in tumor tissue. Cell culture analysis by microscopy and flow cytometry revealed that the prodrug nanogels were efficiently internalized by tumor cells. Distinct release profiles of DOX were achieved by adjusting the nanogel architecture, and online detection of cytotoxicity showed that, unlike free DOX, the dual-responsive prodrug nanogels exhibited a delay in the onset of toxicity, indicating the different uptake mechanism and the need for prodrug activation to induce cell death. PMID- 24225225 TI - The neuropeptide Y Y1 receptor knockdown modulates activator protein 1-involved feeding behavior in amphetamine-treated rats. AB - BACKGROUND: Hypothalamic neuropeptide Y (NPY) and two immediate early genes, c fos and c-jun, have been found to be involved in regulating the appetite suppressing effect of amphetamine (AMPH). The present study investigated whether cerebral catecholamine (CA) might regulate NPY and POMC expression and whether NPY Y1 receptor (Y1R) participated in activator protein-1 (AP-1)-mediated feeding. METHODS: Rats were given AMPH daily for 4 days. Changes in the expression of NPY, Y1R, c-Fos, c-Jun, and AP-1 were assessed and compared. RESULTS: Decreased CA could modulate NPY and melanocortin receptor 4 (MC4R) expressions. NPY and food intake decreased the most on Day 2, but Y1R, c-Fos, and c-Jun increased by approximately 350%, 280%, and 300%, respectively, on Day 2. Similarly, AP-1/DNA binding activity was increased by about 180% on Day 2. The expression patterns in Y1R, c-Fos, c-Jun, and AP-1/DNA binding were opposite to those in NPY during AMPH treatment. Y1R knockdown was found to modulate the opposite regulation between NPY and AP-1, revealing an involvement of Y1R in regulating NPY/AP-1-mediated feeding. CONCLUSIONS: These results point to a molecular mechanism of CA/NPY/Y1R/AP-1 signaling in the control of AMPH-mediated anorexia and may advance the medical research of anorectic and anti-obesity drugs. PMID- 24225228 TI - The Retrograde Tibial Nail: presentation and biomechanical evaluation of a new concept in the treatment of distal tibia fractures. AB - Displaced distal tibia fractures require stable fixation while minimizing secondary damage to the soft tissues by the surgical approach and implants. Antegrade intramedullary nailing has become an alternative to plate osteosynthesis for the treatment of distal metaphyseal fractures over the past two decades. While retrograde intramedullary nailing is a standard procedure in other long bone fractures, only few attempts have been made on retrograde nailing of tibial fractures. The main reasons are difficulties of finding an ideal entry portal and the lack of an ideal implant for retrograde insertion. The Retrograde Tibial Nail (RTN) is a prototype intramedullary implant developed by our group. The implant offers double proximal and triple distal interlocking with an end cap leading to an angle-stable screw-nail construct of the most distal interlocking screw. Its design meets the requirements of a minimally invasive surgical approach, with a stable fracture fixation by multiple locking options. The 8mm diameter curved nail, with a length of 120 mm, is introduced through an entry portal at the medial malleolus. We see possible indications for the RTN in far distal tibial shaft fractures, distal extraarticular metaphyseal tibial fractures and in distal tibia fractures with simple extension into the ankle joint when the nail is combined lag screw fixation. A biomechanical comparison of the current RTN prototype against antegrade nailing (Expert Tibial Nail, Synthes((r)), ETN) was performed. Both implants were fixed with double proximal and triple distal interlocking. Seven biomechanical composite tibiae were treated with either osteosynthesis techniques. A 10mm defect osteotomy 40 mm proximal to the joint line served as an AO 43-A3 type distal tibial fracture model. The stiffness of the implant-bone constructs was measured under low and high extra-axial compression (350 and 600 N) and under torsional load (8 Nm). Results show a comparable stability during axial loading for the two implant types with slightly higher stability in the RTN group. Rotational stability was superior for the RTN. Statistical analysis proved a significant difference (p<0.05) between the ETN and RTN for rotational stability. This study suggests that retrograde tibia nailing with the RTN is a promising new concept for the treatment of distal tibia fractures. PMID- 24225229 TI - The expression and clinical significance of HERC4 in breast cancer. AB - BACKGROUND: Increasing evidence suggest that ubiquitin-proteasome system (UPS) plays a key role in tumorigenesis. HERC4 is a recently identified ubiqutin ligase. However, the expression status and biological functions of HERC4 in cancers are not clearly. METHODS: We evaluated the HERC4 expression in breast cancer cell lines and breast tumor tissues by quantitative real-time PCR and western blot analysis. To investigate the clinicopathological significance of HERC4, immunohistochemistry analysis for HERC4 was performed on a tissue microarray including 13 benign fibroadenoma, 15 intraductal carcinoma, 120 histologically confirmed invasive ductal carcinoma. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of HERC4, when HERC4 positive expression percentage was above 60%, tumor was defined as "positive". RESULTS: HERC4 was up-regulated in breast cancer cell lines and breast tumor tissues compared to non-tumorigenic cell line and adjacent normal breast tissues. According to ROC analysis, HERC4 positive expression was detected in 1/16 (6.3%) of normal breast tissue, in 3/13 (23.1%) of fibroadenoma, in 6/15 (40%) of intraductal carcinoma and 66/120 (55%) of invasive ductal carcinoma. Positive expression of HERC4 was positively correlated with pT status, pN status, clinical stage and histological grade of patients with invasive ductal carcinoma (p < 0.05). CONCLUSIONS: Our findings suggest that HERC4 was a significant diagnostic marker for invasive ductal carcinoma of the breast. PMID- 24225226 TI - Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury. AB - The possibility to control the fate of the cells responsible for secondary mechanisms following spinal cord injury (SCI) is one of the most relevant challenges to reduce the post traumatic degeneration of the spinal cord. In particular, microglia/macrophages associated inflammation appears to be a self propelling mechanism which leads to progressive neurodegeneration and development of persisting pain state. In this study we analyzed the interactions between poly(methyl methacrylate) nanoparticles (PMMA-NPs) and microglia/macrophages in vitro and in vivo, characterizing the features that influence their internalization and ability to deliver drugs. The uptake mechanisms of PMMA-NPs were in-depth investigated, together with their possible toxic effects on microglia/macrophages. In addition, the possibility to deliver a mimetic drug within microglia/macrophages was characterized in vitro and in vivo. Drug-loaded polymeric NPs resulted to be a promising tool for the selective administration of pharmacological compounds in activated microglia/macrophages and thus potentially able to counteract relevant secondary inflammatory events in SCI. PMID- 24225230 TI - 3D Reconstruction of virtual colon structures from colonoscopy images. AB - This paper presents the first fully automated reconstruction technique of 3D virtual colon segments from individual colonoscopy images. It is the basis of new software applications that may offer great benefits for improving quality of care for colonoscopy patients. For example, a 3D map of the areas inspected and uninspected during colonoscopy can be shown on request of the endoscopist during the procedure. The endoscopist may revisit the suggested uninspected areas to reduce the chance of missing polyps that reside in these areas. The percentage of the colon surface seen by the endoscopist can be used as a coarse objective indicator of the quality of the procedure. The derived virtual colon models can be stored for post-procedure training of new endoscopists to teach navigation techniques that result in a higher level of procedure quality. Our technique does not require a prior CT scan of the colon or any global positioning device. Our experiments on endoscopy images of an Olympus synthetic colon model reveal encouraging results with small average reconstruction errors (4.1 mm for the fold depths and 12.1 mm for the fold circumferences). PMID- 24225231 TI - Epidemiology and clinical characteristics of hand foot, and mouth disease in a Shenzhen sentinel hospital from 2009 to 2011. AB - BACKGROUND: We investigated the epidemiological and clinical data of all hand, foot, and mouth disease (HFMD) cases in a sentinel hospital of Shenzhen, China from 2009 to 2011. METHODS: HFMD cases diagnosed in our institution were assessed from 2009 to 2011. Both epidemiological and clinical features were analyzed retrospectively. All the fatal cases were reported. RESULTS: A total of 12132 patients were diagnosed with HFMD, of which 2944 (24.3%) were hospitalized. Of the 2944 hospitalized patients, the highest proportion of diagnosed cases were admitted in May and July (989/2944, 33.6%). In 2009 all severe HFMD cases were diagnosed with enterovirus 71 (EV71). In 2010 and 2011, some of the severe HFMD were diagnosed with Coxsackievirus A16 (CA16). Incidence was highest in 0-4-year old children, with males being predominant. There were sporadic cases with HFMD the whole year except in February. All cases were cured in 2009. Six deaths were reported during 2010 and 2011. CONCLUSIONS: EV71 can cause severe complications and deaths in our region. HFMD is an important public health problem in Shenzhen in spite of stringent measures taken in preschool centers. A high degree of vigilance should be maintained over the disease situation. PMID- 24225232 TI - Control of actin-based motility through localized actin binding. AB - A wide variety of cell biological and biomimetic systems use actin polymerization to drive motility. It has been suggested that an object such as a bacterium can propel itself by self-assembling a high concentration of actin behind it, if it is repelled by actin. However, it is also known that it is essential for the moving object to bind actin. Therefore, a key question is how the actin tail can propel an object when it both binds and repels the object. We present a physically consistent Brownian dynamics model for actin-based motility that includes the minimal components of the dendritic nucleation model and allows for both attractive and repulsive interactions between actin and a moveable disc. We find that the concentration gradient of filamentous actin generated by polymerization is sufficient to propel the object, even with moderately strong binding interactions. Additionally, actin binding can act as a biophysical cap, and may directly control motility through modulation of network growth. Overall, this mechanism is robust in that it can drive motility against a load up to a stall pressure that depends on the Young's modulus of the actin network and can explain several aspects of actin-based motility. PMID- 24225234 TI - [Farnesoid-X-receptor blockade reduces myocardial reperfusion injury in cholesterol-fed apolipoprotein E knockout mice]. AB - OBJECTIVE: To investigate the effect of farnesoid-X-receptor (FXR) antagonist Z guggulsterone in an in vivo high-fat fed apolipoprotein E knockout (ApoE(-/-)) mice model of myocardial ischemia/reperfusion (I/R). METHODS: Male ApoE(-/-) mice were randomly divided into three groups: standard ApoE(-/-) group (fed with standard mouse diet for 12 weeks before myocardial I/R procedure, n = 18), high fat ApoE(-/-) group (fed with high-fat mouse diet for 12 weeks before myocardial I/R procedure, n = 22), and high-fat ApoE(-/-) + FXR antagonist group(fed with high-fat mouse diet for 12 weeks and received FXR antagonist Z-Guggulsterone 30 minutes before myocardial I/R procedure, n = 17). The expression of FXR was detected by real-time quantitative-PCR. Myocardial infarct size was determined by Evans blue/TTC double staining methods. Myocardial apoptosis was determined by in situ TUNEL technique. Markers of the mitochondrial-mediated apoptotic pathway (cytochrome c release, caspase-9 activity, and BAX and BCL-2 levels), endoplasmic reticulum stress apoptotic pathway (caspase-12 activity and CHOP level), and death receptor apoptotic pathway (caspase-8 activity, and Fas and FasL levels) were also measured. RESULT: FXR expression (3.7-fold higher, P < 0.01), myocardial infarct size [(62.1 +/- 7.0)% vs. (33.8 +/- 5.8)%, P < 0.01] and myocardial apoptosis index[ (36.8 +/- 5.7)% vs. (17.2 +/- 3.8)%, P < 0.01]were all significantly higher in high-fat ApoE(-/-) group than those in standard ApoE( /-) group. Compared with high-fat ApoE(-/-) group, myocardial infarct size [(24.4 +/- 4.7)% vs. (62.1 +/- 7.0)%, P < 0.01] and myocardial apoptosis index [(13.8 +/ 2.7)% vs. (36.8 +/- 5.7)%, P < 0.01] were significantly reduced in high-fat ApoE(-/-) + FXR antagonist group. Moreover, levels of mitochondrial-mediated apoptotic pathway markers (cytochrome c release, caspase-9 activity, and BAX/BCL 2 levels) and endoplasmic reticulum stress apoptotic pathway markers (caspase-12 activity and CHOP level) were significantly lower in high-fat ApoE(-/-) + FXR antagonist group than those in high-fat ApoE(-/-) group (all P < 0.01). Levels of death receptor apoptotic pathway markers (caspase-8 activity, and Fas and FasL levels) were similar between high-fat ApoE(-/-) group and high-fat ApoE(-/-) + FXR antagonist group. CONCLUSION: FXR antagonist alleviates myocardial reperfusion injury in cholesterol-fed ApoE(-/-) mice via inhibition of the mitochondrial-mediated and endoplasmic-reticulum stress pathway. PMID- 24225233 TI - Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: efficacy and safety outcomes of a randomized, multi-center phase II study investigating. AB - BACKGROUND: Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. PATIENTS AND METHODS: Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m(2)) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m(2) loading dose one week prior to radiotherapy followed by weekly 250 mg/m(2)). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6-8 weeks after treatment. Toxicity was reported as well. RESULTS: Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months. The OLCR was 84% in Arm A and 92% in Arm B (p=0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p=0.39; OS p=0.99). Toxicity compared equally between both groups. CONCLUSION: The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity. PMID- 24225235 TI - [Pharmacological postconditioning with lactic acid and low dose edaravone could attenuate myocardial reperfusion injury through mitochondrial pathway]. AB - OBJECTIVE: To test the hypothesis that pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper trigger of mechanical postconditioning and relieve reperfusion injury through mitochondrial pathway. METHODS: Rats were randomly divided into 6 groups (n = 18 each): sham, reperfusion/injury(I/R), postconditioning (IP), lactic acid (Lac, 60 ul), low dose edaravone (Eda, 3 ug/kg), and Lac+Eda. After 45 min myocardial ischemia, different drugs or saline were administrated around the infarct border according to different groups using micro syringe at the time of reperfusion. After 10 min reperfusion, right atrial plasma pH value was determined in all rats. Then the rats were sacrificed at 1, 6 and 24 h (n = 6 each), apoptotic index was measured by TUNEL, infarct area and ischemic area were measured through Evans blue-TTC double staining, mitochondrial absorbance, the contents of MDA and SOD in ischemic myocardium were detected by spectrophotometry, and the expression of apoptotic pathway molecules, such as Bcl-2, Bax and Cytochrome c (Cyt-c) , were detected by Western blot. RESULTS: Right atrial plasma pH value was significantly lower, the content of MDA was significantly lower, and the content of SOD was significantly higher in IP and Lac+Eda groups than in I/R group (all P < 0.05). The mitochondrial absorbance in Lac+Eda group at all time points were all significantly higher than those in I/R group (all P < 0.05). The level of Bcl-2 in ischemic myocardium in Lac+Eda group was significantly higher than in I/R group (1.02 +/- 0.19 vs.0.02 +/- 0.01, P < 0.05), the level of Bax (0.38 +/- 0.07 vs.2.40 +/- 0.45, P < 0.05) and Cyt-c(0.78 +/- 0.05 vs.6.54 +/- 1.86, P < 0.05) were all lower than those in I/R group. The content of CK[(849 +/- 228) vs.(1249 +/- 211) U/L, P < 0.05] and CK-MB[(470 +/- 266) vs. (966 +/- 263) U/L, P < 0.05] in Lac+Eda group were all significantly lower than in I/R group, apoptotic index [(10.51 +/- 1.52)% vs. (15.00 +/- 1.90) %, P < 0.05] and infarct area [(27.12 +/- 5.55)% vs. (45.66 +/- 10.81)%, P < 0.05] in Lac+Eda group were all significantly lower than those in I/R group. CONCLUSION: Pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper triggers of mechanical postconditioning and attenuate myocardial reperfusion injury through mitochondrial pathway. PMID- 24225236 TI - [Lycopene protects against hypoxia/reoxygenation-injury by preventing calpain activation]. AB - OBJECTIVE: To investigate the possible mechanism of lycopene on protecting against hypoxia/reoxygenation (H/R)-injury. METHODS: Primary cultured cardiomyocytes, isolated from neonatal mouse, were divided into three groups randomly: control group (C) ; H/R group(4 h H followed by 8 h R); lycopene+H/R group(L+H/R), in which the cardiomyocytes were pretreated with lycopene for 4 h before H/R. The survival of cardiomyocytes was counted. Apoptotic cells were detected by TUNEL assays. The release of cytochrome c from mitochondrial matrix into the cytosol, the activity of caspase-3, intracellular ROS levels and the activity of calpain were also determined in these groups respectively at the same time. RESULTS: The pretreatment of cardiomyocytes with lycopene significantly improved the survival of cardiomyocytes [C: (89.84 +/- 5.15)%, H/R: (63.59 +/- 5.11)%, L+H/R: (79.25 +/- 1.48)%, P < 0.05] and reduced the extent of apoptosis [C: ( 10.37 +/- 1.25)%, H/R: (32.03 +/- 4.79)%, L+H/R: (22.57 +/- 3.22)%, P < 0.05], significantly reduced caspase-3 activation [C: (2.61 +/- 0.19), H/R: (5.82 +/- 0.92), L+H/R: (3.74 +/- 0.64) pNA pmol/ug protein, P < 0.05]. To further study the mechanism underlying the benefits of lycopene, interactions between lycopene and calpain activation were examined. Lycopene pretreatment of cardiomyocytes suppressed the activation of calpain(C:272.33 +/- 300.46, H/R: 1156.00 +/- 212.02, L+H/R: 607.33 +/- 166.23, P < 0.05) by reducing the H/R induced increased intracellular ROS levels [C: 100%, H/R: (239.79 +/- 27.27)%, L+H/R: (188.19 +/- 17.63)%, P < 0.05]. CONCLUSION: Lycopene may protect against hypoxia/reoxygenation-induced injury by preventing calpain activation. PMID- 24225237 TI - [Analyses of super-response to cardiac resynchronization therapy in patients with congestive heart failure: a multiple center trial]. AB - OBJECTIVE: To evaluate the incidence of super-response and the potential predictors related to super-response after cardiac resynchronization therapy (CRT) in patients with congestive heart failure. METHODS: 190 patients [145 men and 45 women;age: (60.48 +/- 11.91) years] underwent CRT between March 2001 and March 2012 were enrolled in this multi-center trial, of which, 54 patients with ischemic cardiomyopathy and 136 patients with non-ischemic cardiomyopathy. These patients were followed up from 6 months to 11 years (mean 58 months) post CRT. RESULTS: Ten patients died within 6 months post CRT, the others were followed up for more than 6 months. At 6-month follow-up, 51 patients were identified as CRT super-responders (28.33%), 75 patients were CRT responders (41.67%) and 29 patients were CRT non-responders (16.11%), and 25 patients were CRT negative responders (13.89%). Super-response occurred more frequently in non-ischemic cardiomyopathy patients, while non-response most commonly occurred in ischemic cardiomyopathy patients (P < 0.05); patients in the negative response group had higher serum creatinine level than other groups (P < 0.05) , and patients in the non-response group and negative response group had higher pulmonary artery pressure than patients in the super-response group (P < 0.05); the average QRS duration was >= 160 ms before CRT, and the mean decrease was around 30 ms after CRT in the super-response group while the average QRS duration was 139 ms before CRT, and the mean reduction was around 8 ms after CRT in the negative response group (P < 0.05). LV lead position in the super-response group was usually in the middle and base of the heart, while in the negative response group it was more commonly located in the apex of the heart (P < 0.01) . CONCLUSIONS: LV lead located at the middle and pre-CRT ORS duration >= 160 ms are associated with super-response post CRT procedure in this patient cohort. PMID- 24225238 TI - [Effects of cardiac resynchronization therapy in patients with advanced congestive heart failure evaluated by real-time 3-dimensional echocardiography]. AB - OBJECTIVE: To quantitatively assess the effects of cardiac resynchronization therapy (CRT) in patients with advanced congestive heart failure by real-time 3 dimensional(3D) echocardiography (RT-3DE). METHODS: Eighteen patients with advanced congestive heart failure underwent CRT with New York Heart association(NYHA) class III and IV and wide QRS complex (>120 ms) were included (17 dilated cardiomyopathy and 1 ischemic cardiomyopathy). Before CRT and 8 months after CRT, the clinical and RT-3DE parameters and outcome were analyzed. RESULTS: The biventricular pacemaker was successfully implanted in 17 patients (94.4%). Compared with before CRT, NYHA class of patients decreased by 1.5 class (P < 0.01), left ventricular ejection fraction increased by 25% (P < 0.01), left ventricular end systolic volume decreased by 38% (P < 0.01), left ventricular systolic dyssynchrony index (SDI) improved significantly (14.2% before CRT vs. 9.8% after CRT, P < 0.01 ) post CRT. Change in SDI and change in LVEF was positively correlated (r = 0.62, P < 0.01) . The procedure complications and outcome during and after CRT included coronary sinus dissection (n = 1), left ventricular lead dislodgement (n = 1), phrenic nerve stimulation (n = 1), sudden cardiac death (n = 1). Three non-response patients were complicated with atrial fibrillation, nonspecific intraventricular block and dilated cardiomyopathy with postero-lateral scar tissue. CONCLUSIONS: CRT could improve the cardiac function, correct the mechanical desynchronization and reverse left ventricular remodeling in patients with congestive heart failure, and SDI quantification by RT-3DE could predict increase of LVEF after CRT, however, there were complications related to the implantation procedure and possibilities of non-response. PMID- 24225239 TI - [Primary experience of treating 23 lone atrial fibrillation patients with a completely thoracoscopic modified Maze procedure]. AB - OBJECTIVE: To evaluate the safety and feasibility of a completely thoracoscopic modified Maze procedure for treatment of patients with lone atrial fibrillation(AF). METHODS: From September 2010 to October 2011, completely thoracoscopic modified Maze procedure was performed in 23 patients with lone atrial fibrillation (14 paroxysmal AF and 9 persistent AF). All patients were either refractory or intolerant to antiarrhythmic drug therapy or already experienced unsuccessful catheter-based ablation. This procedure includes three 1 cm ports for thoracoscopic camera and ablation device on each side of chest wall. Bilaterally pulmonary vine isolation was made by an Atricure TM bipolar radiofrequency device. Two epicardial ablation lines were created on LAPW to connect bilaterally pulmonary vine ablation lesion using Coolrail linear pen. LAA was removed by a Johnson and Johnson EZ45G stapler. RESULTS: The procedures were successful in all the patients, 20 patients were in sinus rhythm immediately after surgery, 2 patients were still in AF rhythm and 1 patient in pacing rhythm post surgery. Three-month follow up were finished in 23 patients and there was 1 patient in AF rhythm, 95.7% patients were free of AF; 6-month follow up were finished in 22 patients, 3 patients were in AF rhythm and 2 patients in AFL rhythm, 77.3% patients were free of AF. CONCLUSION: Our results suggested that the completely thoracoscopic modified Maze procedure is a safe, feasible and effective technique for treating patients with atrial fibrillation. PMID- 24225240 TI - [Value of identifying the slow conduction zone of idiopathic left ventricular tachycardia by electroanatomic mapping]. AB - OBJECTIVE: To explore the value of identifying slow conduction zone(SCZ) of idiopathic left ventricular tachycardia(ILVT) by electroanatomic mapping. METHODS: Twelve patients with ILVT were mapped by a 3-dimensional electroanatomic (EA) mapping system. Left posterior fascicular potential (PP) and the SCZ with diastolic potential (DP) in LV during sinus rhythm (SR) and ventricular tachycardia (VT) were mapped after a three-dimensional endocardial geometry of the left ventricular was established. Then we investigated the electrophysiological and anatomic characteristics of SCZ. RESULTS: EA mapping was successfully performed in 9 patients during SR and VT, and in 3 patients during VT. The SCZ with DP was located at the inferoposterior septum, and the length of the SCZ was (25.1 +/- 2.2) mm with a conduction velocity of (0.08 +/- 0.01) m/s. There was no difference in these parameters between patients during SR and VT (P > 0.05). There was one area with PP located at the posterior septum. The areas with both DP and PP were found in 9 patients during SR and VT. In addition, this area was coincided with such area during VT during SR and radiofrequency ablation targeting the site within the area abolished VT in all patients. CONCLUSIONS: The ILVT substrate within the junction area of the SCZ and the posterior fascicular can be identified by EA mapping and used to guide the ablation of ILVT. PMID- 24225241 TI - [Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients]. AB - OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea >= 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients. PMID- 24225242 TI - [Clinical value of multi-detector computed tomography source image on detecting extracoronary abnormalities]. AB - OBJECTIVE: To assess the clinical value of multi-detector computed tomography (MDCT) source image on detecting extracoronary abnormalities in a large cohort of patients with suspected coronary artery disease (CAD). METHOD: MDCT source images from 3240 consecutive patients (mean 64.5 years) with suspected CAD were reviewed retrospectively by 2 readers.Extra-coronary findings were classified according to involved organ and level of clinical significance.Following organs were examined:lungs, upper abdomen, spine, chest wall, mediastinum and vascularatures. Clinical relevance of extracoronary findings was considered as either "significant" or "non-significant"."Significant" findings were subclassified as score 1:findings necessitating immediate therapeutic actions, or score 2:findings with uncertain clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent)."Non-significant" findings were assigned to score 3:findings without clinical implication. The irrelevant incidental findings (e.g. spinal degenerative changes, aortic calcification) were not analyzed. RESULTS: Extracoronary findings was evidenced in 330 patients with 424 abnormalities, 20.3% (67/330) patients had multiple lesions, 16.5% lesions were located in the lungs, 13.2% lesions found in the upper abdomen, 56.8% (241/424) lesions evidenced in the mediastinum,0.9% (4/424) lesions seen in the spine and chest wall, 13.9% (53/424) lesions were related to other vascular disease. Pleural effusion accounts for 5.5% of the mediastinum lesions.Incidence of heart cavity enlargement, heart valve disease, pericardial effusion/calcification, atrial/ventricular perfusion defects, myocardial disease, congenital heart disease, ventricular aneurysm was 14.7% (56/380), 15.5% (59/380), 10.8% (41/380), 3.9% (15/380), 0.8% (3/380), 1.6% (6/380), and 1.8% (7/380) respectively. The clinical significance score 1-3 was 8.5% (36/424) , 81.1% (344/424) , and 10.4% (44/424) respectively.Incidence of detected extracoronary findings was the highest by bone window and the lowest by lung window.Incidence of extracoronary findings was not related to CAD (chi2 = 81.76, C = 0.155, P > 0.05).Inter-reader agreement on extracoronary findings was excellent (Kappa = 0.934, P > 0.05). CONCLUSION: Our data show that it is of clinical value to observe and report extracoronary findings with source image of cardiac MDCT. PMID- 24225243 TI - [Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats]. AB - OBJECTIVE: To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization(CME) in rats. METHODS: Adult rats were randomly assigned into CME group (intraventricular injection of 3000 microspheres with 42 um in diameter), sham-operated group (0.1 ml saline) and CME plus metoprolol group (pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection, n = 15, each group). Cardiac function was evaluated by echocardiography at 6 hours post various treatments. Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis. RESULTS: Compared with sham-operated group, LVEF (72.68% +/- 3.26% vs. 82.64% +/- 3.43%, P < 0.05), fractional shortening (FS) (37.46% +/- 2.38% vs. 42.85% +/- 3.25%) and cardiac output (CO) [(0.101 +/- 0.006) L/min vs. (0.162 +/- 0.008) L/min] were significantly reduced while left ventricular end-diastolic diameter (LVEDd) [(6.22 +/- 0.17) mm vs. (5.18 +/- 0.43) mm] was significantly increased in CME group (all P < 0.05). Cardiac function [LVEF:73.94% +/- 4.22%, FS:38.53% +/- 2.03%, CO:(0.120 +/- 0.012) L/min, LVEDd:(6.18 +/- 0.27) mm] was similar in CME plus metoprolol group compared to CME group (all P > 0.05). The cardiomyocytes apoptosis rates (3.19% +/- 1.23% vs. 0.18% +/- 0.10%) and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group (all P < 0.05). The cardiomyocyte apoptosis rate (1.32% +/- 0.28%) and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group (all P < 0.05). CONCLUSIONS: Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway. PMID- 24225244 TI - [Stimulation of adenosine A1 receptor attenuates angiotensin II induced myocardial hypertrophy in neonatal rats via the extracellular signal-regulated kinase signal pathways]. AB - OBJECTIVE: To observe the impact of adenosine A1 receptor stimulation on extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathways on angiotensin II (AngII) stimulated cardiomyocytes of neonatal rats in vitro. METHODS: Cardiomyocytes of neonatal rats were cultured in vitro. Cardiomyocytes hypertrophy was induced by AngII (0.1 umol/L). The antihypertrophic effect of adenosine A1 receptor stimulation via adenosine A1 receptor agonist R-PIA (1 umol/L) was observed in the presence or absence of ERK1/2 inhibitor 1, 4-Diamino 2, 3-dicyano-1, 4-bis(o-aminophenylmercapto) butadiene (U0126) 1 umol/L, PKC inhibitor Ro-31-8220 (50 nmol/L), and pertussis toxin (PTX, 5 mg/L). The total protein content was assayed by the method of Lowry. The expression of mRNA of atrial natriuretic peptide (ANP) was determined by RT-PCR. [Ca(2+)]i was measured by confocal microscope using Fluo-3/AM as fluorescent indicator. The relative expression of ERK1/2 was determined by Western blot. RESULTS: Compared with normal control group, AngII induced significant cardiomyocyte hypertrophy. Compared with AngII group, R-PIA significantly inhibited AngII-induced increase of the protein content, cardiomyocytes volume and expression of ERK1/2, calcium ion fluorescence intensity, similar as U0126 and Ro-31-8220. The inhibitory effects on AngII induced cardiomyocytes hypertrophy of R-PIA were lost when preincubated with PTX. CONCLUSION: Adenosine A1 receptor can inhibit AngII induced cardiomyocyte hypertrophy through downregulating ERK signal pathways and reducing intracellular Ca(2+). PMID- 24225245 TI - [Risk factors of congenital heart defects in fetal and infants born from 2004 to 2011 in Guangdong]. AB - OBJECTIVE: To analyze the risk factors of congenital heart defects (CHD) in fetal and infants born from 2004 to 2011 in Guangdong province. METHODS: Babies with CHD aged from 28th week of gestation to 1 year old postnatal from July 1 2004 to December 31 2011 were registered in Guangdong CHD monitoring network with 34 participating units. Totally 2568 CHD cases were included, and 1: 1 matched with a normal control cohort by gender, living district and birth date (time span within 3 months).Exposed information of mother and father at pre-pregnancy and early pregnancy was collected. Post collinearity diagnostics analysis, univariate analysis results were included in a multivariate analysis model with forward stepwise conditional logistic regression. RESULTS: Multivariate conditional logistic regression analysis showed that high risk factors for CHD included low birth weight infant (OR = 5.34, P < 0.01), macrosomia (OR = 1.67, P < 0.05), low per capita income (0-1200 yuan, OR = 1.68, P < 0.01), exposure to chemical agent at early pregnancy (OR = 19.72, P < 0.01), floating population (OR = 2.13, P < 0.01), abnormal reproductive history (OR = 3.18, P < 0.01), exposure to passive smoking (OR = 2.59, P < 0.01), suffering from fever (OR = 3.74, P < 0.01), equal to or more than twice parity (OR = 1.45, P < 0.01), living in a newly (within six months)-decorated-apartment (OR = 2.74, P < 0.01), suffering from virus infection (OR = 2.08, P < 0.01), rural residence (OR = 1.33, P < 0.01), living in an apartment within 50 meters of major traffic road (OR = 1.52, P < 0.01), syphilis infection at early pregnancy (OR = 13.06, P < 0.05) and father's drinking habit at pre-pregnancy (OR = 1.57, P < 0.05). CONCLUSION: Numerous risk factors for CHD in fetal and infants of Guangdong province are indicated by our results, comprehensive intervention should be considered in pre-pregnancy and early pregnancy to reduce the risk of CHD. PMID- 24225246 TI - [Associations between G1165C and A145G polymorphism of beta1-adrenoceptor and resting heart rate in the Northern Han Chinese]. AB - OBJECTIVE: To systematically investigate the possible associations between G1165C and A145G polymorphism of beta1-adrenoceptor (ADRB1) and resting heart rate (HRrest) in Northern Han Chinese. METHODS: HRrest of 700 healthy Northern Han Chinese were measured in the sitting position.SNPs were genotyped by the TaqMan assay.Genotypes were differentiated by analyzing the fluorescence levels of PCR products using an ABI Prism 7900HT Sequence Detector. RESULTS: HRrest was significantly lower in A145G AA carriers than in AG and GG carriers (all P < 0.01) . Multiple linear regression analysis showed that age, smoking habits, systolic blood pressure, triglyceride, serum creatinine and A145G polymorphism were associated with HRrest (P < 0.01) . A145G was significantly related with HRrest independent of other possible confounding variables, and the partial regression coefficient was 2.148 (P < 0.05) . After adjusting for other confounding factors, significant association between A145G and HRrest was only found in male subjects (P < 0.05) but not in female subjects (P > 0.05) . CONCLUSION: The A145G polymorphism of ADRB1 gene is associated with HRrest in Northern male Han Chinese. PMID- 24225247 TI - [Transcatheter closure of residual fistula after second surgery repair of ventricular]. PMID- 24225248 TI - [The clinical and social implications of mutation detection in patients with hypertrophic cardiomyopathy]. PMID- 24225249 TI - [Advance of modern acoustic cardiography in the diagnosis and treatment of heart failure]. PMID- 24225250 TI - Genome-wide survey and expression profiles of the AP2/ERF family in castor bean (Ricinus communis L.). AB - BACKGROUND: The AP2/ERF transcription factor, one of the largest gene families in plants, plays a crucial role in the regulation of growth and development, metabolism, and responses to biotic and abiotic stresses. Castor bean (Ricinus communis L., Euphobiaceae) is one of most important non-edible oilseed crops and its seed oil is broadly used for industrial applications. The available genome provides a great chance to identify and characterize the global information on AP2/ERF transcription factors in castor bean, which might provide insights in understanding the molecular basis of the AP2/ERF family in castor bean. RESULTS: A total of 114 AP2/ERF transcription factors were identified based on the genome in castor bean. According to the number of the AP2/ERF domain, the conserved amino acid residues within AP2/ERF domain, the conserved motifs and gene organization in structure, and phylogenetical analysis, the identified 114 AP2/ERF transcription factors were characterized. Global expression profiles among different tissues using high-throughput sequencing of digital gene expression profiles (DGEs) displayed diverse expression patterns that may provide basic information in understanding the function of the AP2/ERF gene family in castor bean. CONCLUSIONS: The current study is the first report on identification and characterization of the AP2/ERF transcription factors based on the genome of castor bean in the family Euphobiaceae. Results obtained from this study provide valuable information in understanding the molecular basis of the AP2/ERF family in castor bean. PMID- 24225251 TI - The effect of targeted therapy on overall survival in advanced renal cancer: a study of the national surveillance epidemiology and end results registry database. AB - INTRODUCTION: With the advent and availability of targeted therapy, the treatment of advanced/metastatic renal cell carcinoma (RCC) underwent a drastic change in 2005. The effect of this change on clinical outcome within the population has not been studied. The aim of this study was to evaluate the overall survival (OS), before, and after availability of targeted therapy, for advanced RCC cases in the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry. MATERIALS AND METHODS: All advanced (regional and distant stage) RCC cases diagnosed within the 2000 to 2008 time periods were included. Because SEER does not report the exact therapy, and because targeted therapy was initially approved in 2005, we evaluated and compared the OS outcomes of advanced RCC cases diagnosed between the years 2000 and 2003 (before targeted therapy era) with that of those diagnosed between 2005 and 2008 (targeted therapy era). RESULTS: There was a significant improvement in OS for advanced RCC patients treated in the targeted therapy era (n = 12,330) compared with those treated in the era before targeted therapy (n =11,565) (median OS 20 months vs. 15 months, P = .0006). Multivariate analysis revealed that in the time period before targeted therapy, age older than 65 years, black race, and lack of nephrectomy were predictors of a shorter OS. CONCLUSION: In univariate and multivariate analysis, targeted therapy demonstrated improvement in OS. Increasing access to targeted therapies is likely to improve outcomes in advanced RCC. PMID- 24225252 TI - Association between haptoglobin, hemopexin and mortality in adults with sepsis. AB - INTRODUCTION: Plasma levels of cell-free hemoglobin are associated with mortality in patients with sepsis; however descriptions of independent associations with free hemoglobin and free heme scavengers, haptoglobin and hemopexin, are lacking beyond their description as acute phase reactants. We sought to determine the association of plasma levels of endogenous free hemoglobin and haptoglobin and hemopexin with in-hospital mortality in adults with sepsis. METHODS: We conducted a retrospective observational study of a total of 387 critically ill patients with sepsis in multiple intensive care units in an academic tertiary care hospital. Measurements of plasma haptoglobin and hemopexin were made on blood drawn within 24 hours of intensive care unit admission. The primary outcome was the association between plasma haptoglobin and hemopexin with in-hospital mortality. RESULTS: Survivors had significantly higher plasma haptoglobin concentrations (median 1234 MUg/ml, interquartile range (IQR) 569 to 3037) and hemopexin concentrations (616 MUg/ml, IQR 397 to 934) measured on enrollment compared to non-survivors (haptoglobin 750 MUg/ml, IQR 404 to 2421, P = 0.008; hemopexin 470 MUg/ml, IQR 303 to 891, P = 0.012). After controlling for potential confounders including cell-free hemoglobin concentration, patients with higher haptoglobin concentrations were significantly less likely to die in the hospital (odds ratio (OR) 0.653, 95% CI 0.433 to 0.984, P = 0.042), while the same association was not seen with hemopexin (OR 0.53, 95% CI 0.199 to 1.416, P = 0.206). In a subgroup analysis, the association between increased haptoglobin and hemopexin and decreased risk of mortality was no longer significant when analyzing patients with no detectable cell-free hemoglobin (P = 0.737 and P = 0.584, respectively). CONCLUSION: In critically ill patients with sepsis, elevated plasma levels of haptoglobin were associated with a decreased risk of in hospital mortality and this association was independent of confounders. Increased haptoglobin may play a protective role in sepsis patients who have elevated levels of circulating cell-free hemoglobin beyond its previous description as an acute phase reactant. PMID- 24225255 TI - A preference test for sweet taste that uses edible strips. AB - A novel delivery method is described for the rapid determination of taste preferences for sweet taste in humans. This forced-choice paired comparison approach incorporates the non-caloric sweetener sucralose into a set of one-inch square edible strips for the rapid determination of sweet taste preferences. When compared to aqueous sucrose solutions, significantly lower amounts of sucralose were required to identify the preference for sweet taste. The validity of this approach was determined by comparing sweet taste preferences obtained with five different sucralose-containing edible strips to a set of five intensity-matched sucrose solutions. When compared to the solution test, edible strips required approximately the same number of steps to identify the preferred amount of sweet taste stimulus. Both approaches yielded similar distribution patterns for the preferred amount of sweet taste stimulus. In addition, taste intensity values for the preferred amount of sucralose in strips were similar to that of sucrose in solution. The hedonic values for the preferred amount of sucralose were lower than for sucrose, but the taste quality of the preferred sucralose strip was described as sweet. When taste intensity values between sucralose strips and sucralose solutions containing identical amounts of taste stimulus were compared, sucralose strips produced a greater taste intensity and more positive hedonic response. A preference test that uses edible strips for stimulus delivery should be useful for identifying preferences for sweet taste in young children, and in clinical populations. This test should also be useful for identifying sweet taste preferences outside of the lab or clinic. Finally, edible strips should be useful for developing preference tests for other primary taste stimuli and for taste mixtures. PMID- 24225256 TI - A robust design for identification of the Parasite Clearance Estimator. AB - BACKGROUND: Anti-malarial efficacy needs to be monitored continually to ensure optimal dosing in the face of emerging anti-malarial drug resistance. The efficacy of artemisinin based combination therapies (ACT) is assessed by repeated measurements of parasite density in the blood of patients following treatment. Parasite density is measured from a capillary or venous blood sample, but this can be logistically and ethically challenging if multiple samples are required within a short time period. The aim of this work was to apply optimal design theory to derive clinically feasible blood sampling schedules from which parasite clearance could be defined using the Parasite Clearance Estimator (PCE), a recently developed tool to identify and quantify artemisinin resistance. METHODS: Robust T-optimal design methodology was applied to offer a sampling schedule that allows for discrimination across models that best describe an individual patient's parasite-time profile. The design was based on typical parasite-time profiles derived from the literature combined with key sampling constraints of no more than six samples per patient within 48 hours of initial treatment. The design was evaluated with a simulation-estimation procedure that implemented the PCE. RESULTS: The optimal sampling times (sampling windows) were: 0 (0 to 1.1), 5.8 (4.0 to 6.0), 9.9 (8.4 to 11.5), 24.8 (24.0 to 24.9), 36.3 (34.8 to 37.2) and 48 (47.3, 48.0) hours post initial treatment. The simulation-estimation procedure showed that the design supported identification of the appropriate method by the PCE to determine an individual's parasite clearance rate constant (the main output calculation from the PCE). CONCLUSIONS: The proposed sampling design requires six samples per patient within the first 48 hours. The derived design requires validation in a real world setting, but should be considered for future studies that intend to employ the PCE. PMID- 24225254 TI - Determination and comparison of the smallest detectable change (SDC) and the minimal important change (MIC) of four-shoulder patient-reported outcome measures (PROMs). AB - BACKGROUND: There is a need for better interpretation of orthopedic treatment effects. Patient-reported outcome measures (PROMs) are already commonly used for patient evaluation. PROMs can be used to determine treatment effects in research as well as in clinical settings by calculating change scores, with pre- and post treatment evaluation. The smallest detectable change (SDC) and minimal important change (MIC) are two important benchmarks for interpreting these change scores. The purpose was to determine the SDC and the MIC for four commonly used shoulder related PROMs: Simple Shoulder Test (SST), Disabilities of the Arm, Shoulder and Hand (DASH and QuickDASH), and the Oxford Shoulder Score (OSS). METHODS: A cohort of 164 consecutive patients with shoulder problems visiting an orthopedic outpatient clinic completed the SST, DASH, and the OSS at their first visit and 6 months after operative or non-operative treatment. The SDC was calculated with a test re-test protocol (0-2 weeks). For the MIC, change scores (0-6 months of evaluation) were calculated in seven subgroups of patients, according to an additional self-administered ranking of change over time (anchor-based mean change technique). The MIC is defined as the average score of the 'slightly improved' group according to the anchor. The QuickDASH was computed from the DASH. RESULTS: The SDC of the SST was 2.8, DASH 16.3, QuickDASH 17.1, and OSS 6.0. The MIC change score for the SST was 2.2, DASH 12.4, QuickDASH 13.4, and OSS 6.0. CONCLUSION: This study shows that on an individual patient-based level, when taking into account SDC and MIC, the change score should exceed 2.8 points for the SST, 16.3 points for the DASH, 17.1 points for the QuickDASH, and 6.0 points for the OSS to have a clinically relevant change on a PROM, which is not due to measurement error. PMID- 24225257 TI - Malignancies in children and young adults on etanercept: summary of cases from clinical trials and post marketing reports. AB - BACKGROUND: Malignancy risk may be increased in chronic inflammatory conditions that are mediated by tumor necrosis factor (TNF), such as juvenile idiopathic arthritis (JIA), but the role of TNF in human cancer biology is unclear. In response to a 2011 United States Food & Drug Administration requirement of TNF blocker manufacturers, we evaluated reporting rates of all malignancies in patients =30 years old who received the TNF blocker etanercept. METHODS: All malignancies in etanercept-exposed patients aged =30 years from the Amgen clinical trial database (CTD) and postmarketing global safety database (PMD) were reviewed. PMD reporting rates were generated using exposure information based on commercial sources. Age-specific incidence rates of malignancy for the general US population were generated from the Surveillance Epidemiology and End Results (SEER) database v7.0.9. RESULTS: There were 2 malignancies in the CTD: 1 each in etanercept and placebo/comparator arms (both in patients 18-30 years old). Postmarketing etanercept exposure was 231,404 patient-years (62,379 patient-years in patients 0-17 years; 168,485 patient-years in patients 18-30 years). Reporting rates of malignancy per 100,000 patient-years in the PMD and incidence rates in SEER were 32.0 and 15.9, respectively, for patients 0-17 years and 46.9 and 42.1 for patients 18-30 years old. Reporting rates were higher than SEER incidence rates for Hodgkin lymphoma in the 0-17 years age group. PMD reporting rates per 100,000 patient-years and SEER incidence rates per 100,000 person-years for Hodgkin lymphoma were 9.54 and 0.9, respectively, for patients 0-17 years and 1.8 and 4.2 for patients 18-30 years old. There were =5 cases of leukemia, lymphoma, melanoma, thyroid, and cervical cancers. Leukemia, non-Hodgkin lymphoma, melanoma, thyroid cancer, and cervical cancer rates were similar in the PMD and SEER. CONCLUSIONS: Overall PMD malignancy reporting rates in etanercept-treated patients 0-17 years appeared higher than incidence rates in SEER, attributable to rates of Hodgkin lymphoma. Comparison to patients with similar burden of disease cannot be made; JIA, particularly very active disease, may be a risk factor for lymphoma. No increased malignancy reporting rate in the PMD relative to SEER was observed in the young-adult age group. PMID- 24225258 TI - Neuroprotective effect of Ginkgolide K against H2O2-induced PC12 cell cytotoxicity by ameliorating mitochondrial dysfunction and oxidative stress. AB - Mitochondria and oxidative stress play important roles in neuronal cell death associated with cerebral ischemia. Elevated level of reactive oxygen species (ROS) and mitochondrial dysfunction are thought to be responsible for cerebral ischemia injury along with neural cells death through several apoptotic mechanisms. In this study, exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide (H2O2) at the concentration of 0.3 mM for 24 h caused significant loss of cell viability, lactate dehydrogenase (LDH) release from cells, ascent of ROS level and mitochondrial membrane potential (MMP) decrease. Moreover, the activities of caspase-9, caspase-8 and caspase-3 all were increased in H2O2-induced PC12 cells. However, pretreatment with ginkgolide K (GK) solutions of different concentrations (10, 50, 100 uM) for 24 h prior to exposuring to H2O2 significantly increased cells viability, suppressed LDH release, attenuated ROS level, prevented cytochrome c release from mitochondria and boosted MMP expression. In addition, ginkgolide K notably inhibited the caspase-3 and caspase-9 but not caspase-8 activities in exogenous H2O2-treated PC12 cells. These results demonstrated that ginkgolide K protected PC12 cells from H2O2-induced apoptosis by restoring MMP expression, ameliorating oxidative stress and subsequently leading to inhibit the activity of caspase-3 protein. Therefore, the present study supported that ginkgolide K may be a promising neuroprotective compound for cerebral ischemia treatment. PMID- 24225259 TI - Comparative study of novel ultradeformable liposomes: menthosomes, transfersomes and liposomes for enhancing skin permeation of meloxicam. AB - In the present study, novel ultradeformable liposomes (menthosomes; MTS), deformable liposomes (transfersomes; TFS) and conventional liposomes (CLP) were compared in their potential for transdermal delivery of meloxicam (MX). MTS, TFS and CLP were investigated for size, size distribution, zeta potential, elasticity, entrapment efficiency and stability. In vitro skin permeation using hairless mice skin was evaluated. Vesicular morphology was observed under freeze fractured transmission electron microscopy (FF-TEM). Intrinsic thermal properties were performed using differential scanning calorimetry (DSC) and X-ray diffraction. The skin permeation mechanism was characterized using confocal laser scanning microscopy (CLSM). The results indicated that the difference in physicochemical characteristics of MTS, TFS and CLP affected the skin permeability. MTS and TFS showed higher flux of MX than CLP. CLSM image showed deformable vesicles mechanism for delivery of MX across the hairless mice skin. Our study suggested that ultradeformable and deformable liposomes (MTS and TFS) had a potential to use as transdermal drug delivery carriers for MX. PMID- 24225260 TI - Serum prolidase enzyme activity and oxidative status in patients with Behcet's disease. AB - OBJECTIVES: To assess serum prolidase enzyme activity and oxidative stress in patients with Behcet's disease (BD). METHODS: The study population consisted of BD patients (n = 42) and healthy participants (n = 29). BD patients were classified as active (n = 18) or inactive (n = 24) according to disease activity. Serum prolidase enzyme activity, total antioxidant status (TAS), total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA) levels were measured. RESULTS: In BD patients with active disease, serum prolidase activity was significantly higher compared with the inactive and control participants. Serum prolidase activity was also significantly higher in all BD patients in comparison with controls. Serum prolidase activity was also positively correlated with OSI, C-reactive protein, and active BD. MDA, TOS, and OSI levels were all significantly higher in the BD group when compared with the healthy control participants. Serum TAS levels were significantly lower in BD patients in comparison with healthy controls. CONCLUSION: High prolidase activity may indicate critical biological activities relevant to pathological events in BD, and this activity may be a biological indicator of disease. Further studies are needed to verify these findings. PMID- 24225261 TI - High prevalence of hepatitis B virus dual infection with genotypes A and G in HIV 1 infected men in Amsterdam, the Netherlands, during 2000-2011. AB - BACKGROUND: Hepatitis B virus (HBV) is divided into 8 definite (A-H) and 2 putative (I, J) genotypes that show a geographical distribution. HBV genotype G, however, is an aberrant genotype of unknown origin that demonstrates severe replication deficiencies and very little genetic variation. It is often found in co-infections with another HBV genotype and infection has been associated with certain risk groups such as intravenous drug users and men having sex with men (MSM). We aimed to estimate the prevalence of HBV-G in the Netherlands by analysing samples from HBV-positive patients visiting the Academic Medical Center in Amsterdam. METHODS: Ninety-six HBV-infected patients, genotyped as HBV-A or HBV-G infected, were retrieved from the clinical database. Blood plasma samples were analysed with a newly-developed real-time PCR assay that detects HBV-A and HBV-G. For three patients, the HBV plasma viral load (pVL) of both genotypes was followed longitudinally. In addition, three complete genomes of HBV-G were sequenced to determine their relationship to global HBV-G strains. RESULTS: Ten HBV-G infections were found in the selected Dutch patients. All concerned HIV-1 infected males with HBV-A co-infection. Dutch HBV-G strains were phylogenetically closely related to reference HBV-G strains. CONCLUSIONS: In this study, HBV-G infection in the Netherlands is found exclusively in HIV-1 infected men as co infection with HBV-A. A considerable percentage (37%) of men infected with HBV and HIV-1 are actually co- infected with two HBV genotypes. PMID- 24225262 TI - The effects of mode of delivery and time since birth on chronic pelvic pain and health-related quality of life. AB - OBJECTIVE: To assess the effects of mode of delivery and time since birth on chronic pelvic pain (CPP) and health-related quality of life (HRQoL) among primiparous Chinese women. METHODS: Primiparous women of childbearing age who had given birth at least 6months previously were invited to participate in the present cross-sectional study, which was conducted from October 2011 to April 2012 in the Chaoyang District of Beijing. Time since birth was divided into the following 4 periods: less than 1year, 1-5years, 6-10years, and more than 10years. The factors associated with CPP status were analyzed using logistic regression. RESULTS: Among the 1456 participants, CPP was more common following cesarean delivery (11.2% versus 6.9% among women with a vaginal delivery; P=0.007), and the rate of CPP increased with time since birth (2.3%, 9.3%, 10.7%, and 13.1% for the 4 specified time periods, respectively (P<0.001). Cesarean delivery, longer time since birth, and CPP were all associated with a lower HRQoL utility score. CONCLUSION: Although the absolute risks were small, cesarean delivery and time since birth were significant risk factors for CPP, which had a negative impact on the participants' HRQoL. PMID- 24225263 TI - Parenteral nutrition utilization: response to drug shortages. PMID- 24225264 TI - Peripherally inserted central catheter for use in home parenteral nutrition: a 4 year follow-up study. AB - BACKGROUND: Peripherally inserted central catheters (PICCs) are a relatively new device for home parenteral nutrition (HPN). Usually, tunneled central catheters such as the Hickman catheter are used for this purpose. However, severe complications (eg, pneumothorax) have been reported in association with the insertion of the central catheter. In contrast, PICCs may offer some advantages due to the peripheral insertion. There are only few studies on the use of PICCs for HPN. METHOD: A retrospective study (2008-2012) was performed in our Center for Nutrition and Bowel Disease. Patients receiving parenteral nutrition through PICCs were identified, their files examined, and indication, dwell time, cause of removal, and complications recorded. RESULTS: Fifty-six patients (aged 28-81 years) had a total of 94 lines. Total catheter days were 9859. Mean catheter days per patient were 179.1, and mean dwell time of each line was 104.9 days (longest, 572 days). There were no major complications in relation to the insertion of the catheters. The catheters were removed due to catheter-related sepsis, mechanical reasons, and thrombotic complications in 1.7, 2.1, and 0.2 per 1000 catheter days, respectively. CONCLUSION: This study demonstrates that PICCs are appropriate for use in HPN for at least 3-4 months (a period that sometimes unexpectedly becomes long term). The complications equal those reported for tunneled central catheters. We conclude that PICCs are a relevant alternative to patients receiving HPN, especially if they cannot handle a central line. At present, the choice of catheter must be determined on an individual basis. PMID- 24225265 TI - Comparison of the accuracy of digital stereophotogrammetry and projection moire profilometry for three-dimensional imaging of the face. AB - The aim of this study was to compare the three-dimensional (3D) imaging accuracy between a digital stereophotogrammetry device and a projection moire profilometry setup using anatomical models in conjunction with surface matching software. Twenty-two 3D surface models of the middle third of the face derived from computed tomography (CT) scans were used to fabricate photopolymer models by rapid prototyping. These were digitized using digital stereophotogrammetry and projection moire profilometry. The 3D surface models acquired were compared for shape differences with the original CT models using surface matching software. Global registration between each pair of corresponding models was carried out using an iterative closest point algorithm. The mean surface deviations following registration were used to calculate Bland-Altman limits of agreement between the two methods. The distributions of measured surface differences were used to calculate L-moments. Paired t-tests were carried out for hypothesis testing. Correlation between difference and mean was -0.3, and 95% limits of agreement were -0.084mm and 0.064mm. No statistically significant differences in mean measurement error (L1 moments) were observed (P=0.1882). The experimental moire profilometry setup employed produced 3D models of facial anatomy of comparable accuracy to a widely used commercialized digital stereophotogrammetry device. PMID- 24225266 TI - Idiopathic granulomatous mastitis: a rare entity with a variable presentation. AB - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, chronic benign breast disease which may mimic a breast abscess or malignancy. It is a diagnosis of exclusion, and requires a high index of suspicion. Most patients present in the third or fourth decade of life. CASE SERIES: We present a case series of IGM with varied presentation, as a non-resolving abscess and as a lump, clinically appearing to be malignant. Patients required repeated drainage and/or lumpectomy. CONCLUSION: Although IGM is considered to be autoimmune in aetiology, however other infectious aetiologies causing granulomatous mastitis and malignancy have to be ruled out by histopathology. In the event of relapse immunosuppression may be required. PMID- 24225268 TI - Collaboration, capacity building and co-creation as a new mantra in global health. PMID- 24225267 TI - Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: interdisciplinary approaches. AB - Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about overtreatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of overdiagnosis among some women and failure of early detection among others. These concerns are heightened by the multifold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS. PMID- 24225269 TI - Association of healthcare expenditures with aggressive versus palliative care for cancer patients at the end of life: a cross-sectional study using claims data in Japan. AB - BACKGROUND: End-of-life (EOL) care imposes heavy economic burdens on patients and health insurers. Little is known about the association between the types of EOL care and healthcare costs for cancer patients across various providers. OBJECTIVE: To explore the association of healthcare expenditures with benchmarking indicators of aggressive versus palliative care among terminally ill cancer patients, from the perspective of health insurers. DESIGN: Cross-sectional retrospective study using health insurance claims data. SETTING: participants Cancer patients who had died in Kyoto prefecture, Japan, between April 2009 and May 2010. Main outcome measure Claims data were analyzed using multilevel generalized linear models to examine whether aggressive care and palliative care were associated with expenditures during the last 3 months of life, after adjusting for patient characteristics, hospital characteristics and other non indicator procedures. RESULTS: We analyzed 3143 decedents from 54 hospitals. Median expenditure per patient during the last 3 months was US$13 030. Higher expenditures were associated with the aggressive care indicators of higher mortality at acute-care hospitals and use of chemotherapy in the last month of life, as well as with the palliative care indicators of increased hospice care and opioid use in the last 3 months of life. However, increased physician home care in the last 3 months was associated with lower expenditure. CONCLUSIONS: Indicators of both aggressive and palliative EOL care were associated with higher healthcare expenditures. These results may support the coherent development of measures to optimize aggressive care and reduce the financial burdens of terminal cancer care. PMID- 24225270 TI - Associations between rates of unassisted inpatient falls and levels of registered and non-registered nurse staffing. AB - OBJECTIVE: To enhance understanding of how nurse staffing relates to unassisted falls by exploring non-linear associations between unassisted fall rates and levels of registered nurse (RN) and non-RN staffing on 5 nursing unit types, thereby enabling managers to improve patient safety by making better-informed decisions about staffing. DESIGN: Cross-sectional analysis of routinely collected data using hierarchical negative binomial regression. SETTING: 8069 nursing units in 1361 U.S. hospitals participating in the National Database of Nursing Quality Indicators((r)). Main outcome measure Rate of unassisted falls per inpatient day. RESULTS: Associations between unassisted fall rates and nurse staffing varied by unit type. For medical-surgical units, higher RN staffing was weakly associated with lower fall rates. On step-down and medical units, the association between RN staffing and fall rates depended on the level of staffing: At lower staffing levels, the fall rate increased as staffing increased, but at moderate and high staffing levels, the fall rate decreased as staffing increased. Higher levels of non-RN staffing were generally associated with higher fall rates.. CONCLUSIONS: Increasing non-RN staffing seems ineffective at preventing unassisted falls. Increasing RN staffing may be effective, depending on the unit type and the current level of staffing. PMID- 24225271 TI - Trends in resting pulse rates in 9-11-year-old children in the UK 1980-2008. AB - OBJECTIVE: Little is known about whether levels of physical fitness, which is related to adiposity and physical activity (PA), have changed in children, particularly the progressive increase in childhood obesity levels. We aimed to examine the time trends in resting pulse rate (a marker of physical fitness) among UK children, in order to better understand the trends in levels of physical fitness in recent decades. DESIGN AND SETTING: We used a cross-sectional study design and included data on over 22 000 children aged 9-11 years (mean 10.3 years) from five population-based studies conducted in the UK between 1980 and 2008. MAIN OUTCOME MEASURES: Resting pulse rate (bpm). RESULTS: Observed mean resting pulse rate was higher for girls than boys (82.2 bpm vs 78.7 bpm). During the study period mean pulse rate increased by 0.07 bpm/year (95% CI 0.04 to 0.09) among boys and to a lesser extent among girls, by 0.04 bpm/year (0.01 to 0.06) (p<0.05 for gender interaction). For boys, there was an indication that the trend was steeper after the mid-1990 s, compared to that prior to 1994 (annual increase 0.14 vs 0.04 bpm). The trends for Body Mass Index (BMI) accounted for only 13.8% (11.3% to 16.3%) of increase in pulse rate for boys and 17.2% (9.4% to 24.9%) for girls. CONCLUSIONS: Increases in mean resting pulse rate have occurred during the period 1980-2008 in girls and especially in boys. The increase was not explained by increased BMI. The observed trends in children, though modest, could have important public health implications for future cardiovascular risk. PMID- 24225272 TI - No evidence of an increase in early infant mortality from congenital adrenal hyperplasia in the absence of screening. AB - OBJECTIVE: Congenital adrenal hyperplasia (CAH) is not currently included in the UK newborn screening programme. We investigated the hypothesis that, owing to non specificity of symptoms, a proportion of males affected by salt-wasting (SW) CAH have died in infancy without being diagnosed. DESIGN: Stored newborn screening blood spot samples were analysed for 17alpha-hydroxyprogesterone (17-OHP) in the following groups: Infants born in the North West of England, 1994 to 2006, who had died by 6 months age; (n=1198), a neonatal reference group (full-term n=100; preterm n=100) and a CAH positive control group. A newborn blood spot sample collected before diagnosis was available in 29/61 CAH patients recruited. SW CAH was present in 18/29 patients (16 males and 2 females). Samples from the deceased group with elevated 17-OHP were analysed for 8 common mutations in the 21 hydroxylase gene (CYP21A2). SETTING: North West of England. RESULTS: Grouped by gestational age, mean (maximum) blood spot 17-OHP in nmol/L was as follows. Deceased full-term n=279, 6 (107); deceased premature n=365, 28 (251); deceased unknown gestational age n=553, 13 (>394). In the SW positive control group, the lowest level of 17-OHP was 179 nmol/L and 14 had levels greater than the highest standard (>268 to >420 nmol/L). All samples from the deceased group with 17-OHP results >179 nmol/L (n=6) and a further 13 samples underwent mutation analysis. No mutations were identified. CONCLUSIONS: Our findings do not support the hypothesis that, in our unscreened population, males affected by SW CAH are dying prior to diagnosis. PMID- 24225273 TI - Self-harm: are we doing enough? PMID- 24225274 TI - Undescended testis: 513 patients' characteristics, age at orchidopexy and patterns of referral. AB - OBJECTIVE: Undescended testis (UDT) affects 1-6% of males. Current recommendations are to correct maldescent by 1 year of age. We identify the population characteristics of children referred and managed for UDT, age at referral and orchidopexy, and patterns of referral. DESIGN, SETTING AND PATIENTS: Retrospective 5-year review of all patients operated for UDT from 2007 to 2011 in our institution. Patient demographics, neonatal diagnosis of UDT, age at referral, referral source and age at first orchidopexy were recorded. Data are reported as median (range). RESULTS: There were 513 boys with 576 undescended gonads; 450 (88%) had unilateral UDT. Congenital (present at birth) UDT was diagnosed in 287 (56%) children. Seventy-nine (15%) were premature births, 41 (8%) had associated major genitourinary abnormalities. Median age at referral was 1.1 (0-16.2) years; median age at first orchidopexy was 1.6 (0-17.2) years. When corrected for age, those with a history of prematurity and associated major genitourinary malformations were referred and operated on earlier. There was no difference in age at referral and orchidopexy when comparing unilateral versus bilateral maldescent, and palpability of UDT. Of those with congenital UDT, 70% were operated at beyond 1 year of age. Those referred from public tertiary hospitals were younger than those referred from community clinics (p<0.0001) and private healthcare institutions (p=0.003). CONCLUSIONS: Despite early diagnosis in many patients with UDT, most are referred and operated after 1 year of age, even in congenital UDT. Premature babies, those with major genitourinary anomalies, and those seen in public tertiary hospitals are referred earlier. Community health initiatives must emphasise prompt referral to allay the impact of delayed surgery. PMID- 24225275 TI - Can foster care ever be justified for weight management? AB - Article nine of the UN Convention of the Rights of the Child states that 'Children must not be separated from their parents unless it is in the best interests of the child.' We describe the impact that placing a child into care can have on long-standing and intractable obesity when this is a component of a child safeguarding strategy. Significant weight loss was documented in a male adolescent following his placement into foster care due to emotional harm and neglect within his birth family. The child's body mass index (BMI) dropped from a peak of 45.6 to 35 over 18 months. We provide brief details of two further similar cases and outcomes. Childhood obesity is often not the sole concern during safeguarding proceedings. Removal from an 'obesogenic' home environment should be considered if failure by the parents/carers to address the obesity is a major cause for concern. It is essential that all other avenues have been explored before removing a child from his birth family. However, in certain circumstances we feel it may be justified. PMID- 24225276 TI - Association of carbamazepine-induced severe cutaneous drug reactions and HLA B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore. AB - OBJECTIVES: To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. METHOD: Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. RESULTS: HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to infinity). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7 12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. CONCLUSIONS: HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses. PMID- 24225277 TI - Simplifying and refining the assessment of early puberty. PMID- 24225279 TI - Trocar site hernia after laparoscopy, including robotic-assisted laparoscopy. PMID- 24225278 TI - How is epigenetic information maintained through DNA replication? AB - DNA replication is a highly conserved process that accurately copies the genetic information from one generation to the next. The processes of chromatin disassembly and reassembly during DNA replication also have to be precisely regulated to ensure that the genetic material is compactly packaged to fit into the nucleus while also maintaining the epigenetic information that is carried by the histone proteins bound to the DNA, through cell divisions. Half of the histones that are deposited during replication are from the parental chromatin and carry the parental epigenetic information, while the other half of the histones are newly-synthesized. It has been of growing interest to understand how the parental pattern of epigenetic marks is re-established on the newly synthesized histones, in a DNA sequence-specific manner, in order to maintain the epigenetic information through cell divisions. In this review we will discuss how histone chaperone proteins precisely coordinate the chromatin assembly process during DNA replication. We also discuss the recent evidence that histone modifying enzymes, rather than the parental histones, are themselves epigenetic factors that remain associated with the DNA through replication to re-establish the epigenetic information on the newly-assembled chromatin. PMID- 24225280 TI - Trocar site hernia on an 8-mm port following robotic-assisted hysterectomy. AB - The increasing use of laparoscopy has resulted in added complications specific to the laparoscopic approach, such as trocar site hernia (TSH), which is an uncommon but well-recognized problem for both regular laparoscopic and robotic-assisted laparoscopic procedures. We describe an extremely rare case of TSH at an 8-mm port site occurring a relatively short time after surgery in a 53-year-old patient undergoing robotic-assisted laparoscopic hysterectomy for benign reasons. Additionally, this report attempts to explain the possible etiological factors relating to TSH following robotic-assisted surgery. According to our case report, a defect in the 8-mm port that may lead to hernia is one possible explanation, and closure of the 8-mm trocar sites' fascia may be a safer approach during robotic-assisted surgery. Additional reports are needed to accurately determine the frequency of occurrence and importance of this complication. PMID- 24225281 TI - Lipopolysaccharide binding protein in cirrhotic patients with severe sepsis. AB - BACKGROUND: Lipopolysaccharide binding protein (LBP) is an acute-phase protein produced by the liver. It has been shown that LBP plays an important role in the inflammatory response to sepsis. LBP has also been shown to protect animals from endotoxin challenge by facilitating the removal of endotoxin from the blood circulation. Cirrhotic patients are susceptible to bacterial infection. It is unknown whether pre-existing liver dysfunction impacts the LBP levels and thus the prognosis in severe sepsis. METHODS: We evaluated the serum LBP, inflammatory cytokines, and the relationship between LBP concentrations, functional liver reserve and outcomes in 58 critically ill cirrhotic patients with severe sepsis. RESULTS: The serum LBP levels were significantly higher in 28-day survivors, while the interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly higher in non-survivors. We analyzed the receiver operating characteristic (ROC) curve to determine the cut-off point for LBP to predict 28 day mortality. The cumulative rates at 28 days were 58.3% versus 16.7% for the high LBP group (>46 ng/mL) and low LBP group (<46 ng/mL) (p < 0.001). The high LBP group had significantly lower INR, Child-Pugh, Model for End-stage Liver Disease (MELD) scores and TNF-alpha level. Meanwhile, the LBP levels were inversely correlated with INR, and Child-Pugh, MELD and sequential organ failure assessment (SOFA) scores. CONCLUSION: The concentration of LBP is associated inversely with disease severity scores and outcomes in critically ill cirrhotic patients with severe sepsis. PMID- 24225282 TI - Occurrence of atrioventricular block during supraventricular tachycardia: What is its possible mechanism? AB - A female patient was admitted to our hospital for catheter ablation arising from paroxysmal supraventricular tachycardia (PSVT). In the laboratory, PSVT (the earliest retrograde atrial activation at the coronary sinus ostium) with intermittent atrioventricular (AV) block could be induced repeatedly. The tachycardia could be terminated during ventricular pacing without retrograde conduction to the atria. Therefore, orthodromic AV reciprocating tachycardia (AVRT) and atrial tachycardia (AT) could be ruled out and AV nodal re-entrant tachycardia (AVNRT) was subsequently considered. Initial attempts using slow or intermediate AV nodal ablation failed to cure the tachycardia. We considered the possibility of orthodromic AV reciprocating tachycardia (AVRT) with AV block occurring during the tachycardia. The tachycardia was successfully terminated during the ablation of the right posteroseptal pathway at the coronary sinus ostium. We hypothesized about the possible explanation that might help to clarify the phenomenon of AV block during SVT in order to provide some guidance to other clinicians confronted with similar patient challenges in the future. PMID- 24225283 TI - [Further improve the level of the etiological diagnosis of pediatric cardiomyopathy]. PMID- 24225284 TI - [Promote multidisciplinary study on anthracycline-induced cardiotoxicity in children]. PMID- 24225285 TI - [To attach great importance to clinical management of Kawasaki disease with coronary arterial lesions]. PMID- 24225286 TI - [Meta-analyses of the associations of genome-wide association study- linked gene loci with Kawasaki disease]. AB - OBJECTIVE: Kawasaki disease (KD) is a common autoimmune vasculitis. It has been regarded as the leading cause of acquired heart disease in children. This study aimed to assess the relationship between genome-wide association study (GWAS) linked gene loci and KD. METHOD: By March of 2013, the published GWAS literatures of KD were retrieved from the databases including PubMed, MEDLINE, Web of Science, Cochrane Library, CNKI, VIP and Wanfang, and the gene loci associated with KD at genome-wide significance of P < 5.0*10(-8) were determined. For each of the gene loci, one single-nucleotide polymorphism (SNP) with strong association with KD was chosen for meta-analysis. Then the published case-control studies reporting the associations of the SNPs with KD were collected from English and Chinese databases with the same criteria. The Meta-analyses were conducted with RevMan 5.1 software after screening and evaluation. RESULT: A total of 4 gene loci including FCGR2A, BLK, CD40 and HLA were observed having association with KD at genome-wide significance of P < 5.0*10(-8) in at least one GWAS. The risk alleles of the SNPs in the gene loci were all more common in patients with KD relative to controls in the systematic reviews with 8, 4, 6 and 4 extracted case-control studies, respectively[ FCGR2A rs1801274: P < 0.001, OR = 1.40, 95% CI (1.30, 1.51); BLK rs2254546: P < 0.001, OR = 1.69, 95% CI (1.52, 1.88); CD40 rs4813003: P < 0.001, OR = 1.31, 95% CI (1.22, 1.41); HLA rs2857151: P < 0.001, OR = 1.41, 95% CI (1.27, 1.57)]. The significant publication bias was not observed in the meta-analyses. CONCLUSION: Our results confirmed the overall association of the 4 gene loci with KD in observed populations, together with the consistent presence of the relationship between BLK or HLA and KD in the populations, suggesting that it is hopeful to find the genetic marker combination predicting the risk of KD, the formation of secondary coronary artery lesions and the resistance of intravenous immunoglobulin, by further seeking the function SNPs of the gene loci and investigating the effect on the important clinical phenotypes of KD. PMID- 24225287 TI - [Left atrial and ventricular epicardial dual chamber pacing through a left lateral thoracotomy to treat pediatric complete atrioventricular block]. AB - OBJECTIVE: To investigate the feasibility, advantages and efficacy of implantation of left atrial and ventricular epicardial dual chamber pacemaker to treat pediatric complete atrioventricular block. METHOD: Eleven children with median age 4.0 years (0.5-7.6 years) diagnosed as complete atrioventricular block resisting to drug therapy received implantations of left atrial and ventricular epicardial dual chamber pacemakers. Six were male and five female. Temporal or permanent right ventricular pacing was used for all of them before implantation of left atrial and ventricular epicardial dual chamber pacemakers. Three cases showed cardiac dysfunction. Left lateral thoracotomy was performed at 4th intercoastal space along anterior axillary line under general anesthesia, the pericardium was incised vertically anterior to the phrenic nerve, two pacing leads were individually located at left atrial appendage and left ventricular lateral wall. After all the parameters were detected to be satisfactory, a pouch was made at left abdomen under coastal margin. Dual chamber pacemaker was connected with pacing leads through subcutaneous tunnels. The sizes of heart chambers, cardiac functions, parameters of pacemaker, sensitivity, pacing status, PR interval and QRS interval were closely followed up post-operatively. RESULT: Implantations of pacemakers were successful for all of the patients with no complications associated with operations. Preoperative electrocardiograms showed QRS interval (180 +/- 33)ms under right ventricular pacing, it decreased to (140 +/- 24)ms after implantation of left atrial and ventricular epicardial dual chamber pacemaker, significantly lower than right ventricular pacing (t = 8.8, P < 0.05) . Atrioventricular (AV) interval was set at 90 ms, PR interval (124 +/- 4)ms. Echocardiograms performed within 2-3 days after implantation of left atrial and ventricular epicardial dual chamber pacemakers showed that for the 3 cases who were previously under right atrial and right ventricular dual chamber pacing presenting cardiac dysfunction, their left ventricular diastolic diameter (LVDd) decreased from (46.3 +/- 12.5) (32.0-55.0) ms to (44.7 +/- 12.0) (31.0-53.0) mm and left ventricular ejection fraction (LVEF) increased from 30% +/- 15% (18% 47%) to 44% +/- 18% (33%-65%). During 2-14 months' follow up, LVEF increased progressively which became significantly higher than before (65% +/- 8% vs. 30% +/- 15%, t = 5.6, P < 0.05) . Cardiac chamber sizes and left ventricular systolic function for the other 8 patients maintain normal during follow up. Pacing status and sensitivity were satisfactory for all these patients during follow up. CONCLUSION: Implantation of left atrial and ventricular epicardial pacemaker might be considered for children diagnosed as complete atrioventricular block for whom endocardial pacemaker could not be implanted, due to its utmost protection for cardiac function with minimal injury and its ability to prevent or reverse pacemaker syndrome. Left atrial and left ventricular epicardium should be regarded as the first-choice and routine locations for epicardial pacing. PMID- 24225288 TI - [Perinatal integrative intervention for critical pulmonary artery valve stenosis]. AB - OBJECTIVE: To investigate the effect of different operation time to percutaneous balloon pulmonic valvuloplasty (PBPV) to critical pulmonary valve stenosis (CPS). METHOD: Twenty-one infants (age <= 60 days at operating day) suffered from CPS, diagnosed by fetal echocardiogram and confirmed by echocardiography after birth, were enrolled in this case-control-study with written informed consent during April 2007 to December 2011. Of the 21 cases, 7 had prenatal diagnosis in our prenatal diagnosis center (prenatal group, Pre) and 14 were referred from other hospitals, who were divided into postpartum group A (Post A, referred within 28 days after birth) and postpartum group B (Post B, referred 29 to 60 days after birth). To Pre-group, the integrative interventional protocol was cautiously made by the consultative specialists, including intrauterine diagnosis, perinatal care and urgent PBPV soon after birth. To Post-group, emergency PBPV was preformed after the referral. Tei index of right ventricular and pressure-gradient (PG) between right ventricular and pulmonary artery were measured before and at different time points one year after PBPV. RESULT: The values of SpO2 in Pre group ranged from 82%-92% (86.57% +/- 5.34%) under the state of continuous intravenous infusion of alprostadil. PBPV was successfully preformed within 3-6 days after birth. The values of SpO2 increased to 97.33% +/- 1.15% post procedure. The values of PG pre- and post- procedure were (86.34 +/- 11.77) mm Hg and (31.43 +/- 8.46) mm Hg respectively. Preoperative RV Tei-index was 0.68 +/- 0.05, it decreased rapidly after procedure, and recovered to normal one month after procedure. Only one case showed restenosis seven months after procedure and repeated PBPV. Fourteen referral cases (6 cases in Post A group and 8 cases in Post B group, accompanied in 1 and 3 cases with heart failure), the values of SpO2 ranged from 83%-91% under state of continuous intravenous infusion of alprostadil. And the operating time was 10-57 days after birth. The values of SpO2 recovered to normal post procedure, and heart failure alleviated. Increased preoperative RV pressure obviously decreased significantly post-procedure. And increased Tei-index declined gradually, at one-year follow-up, the value of Tei index in Post A group recovered to normal, whereas that of Post B was (0.51 +/- 0.06), compared to Pre and Post A groups, the difference was significant (P < 0.05) . One case showed restenosis nine months after procedure and repeated PBPV was performed. The hypoxic exposure durations were (4.43 +/- 0.68) , (16.33 +/- 4.46) , (41.25 +/- 9.19) , respectively, and the difference among the three groups was significant (P < 0.05). CONCLUSION: To the fetuses with definite prenatal diagnosis of critical pulmonary valve stenosis, preoperative general condition can be adjusted to more suitable for emergency operation. Early PBPV can achieve shorter hypoxic exposure and better recovery of right ventricular function post procedure. Perinatal integrated intervention for CPS can significantly improve the prognosis and quality of life in this patient population. PMID- 24225290 TI - [Recommendations for gene assays for cardiomyopathy in children]. PMID- 24225289 TI - [Budd-Chiari syndrome in children and adolescents: therapeutic radiological intervention]. AB - OBJECTIVE: Due to its minimal-invasive approach, endovascular procedure had replaced surgery in treating Budd-Chiari syndrome (BCS). The interventional therapy was a safe and effective treatment in adults with BCS and the cure rate was high. However Budd-Chiari syndrome in children and adolescents is rare. Published literature on interventional procedure for Budd-Chiari syndrome in children and adolescents is scarce. The aim of the study was to present results of percutaneous transluminal angioplasty (PTA) and stents placement in children and adolescents with BCS and to evaluate the efficacy and safety in these patients of this approach. METHOD: Twenty-five patients [16 boys and 9 girls; average age of (14.5 +/- 3.4) years old; age ranged from 5 to 17 years] with Budd Chiari syndrome who were hospitalized from December 1990 to August 2012 were presented. All of them were diagnosed by color Doppler ultrasound scan while 12 of them had magnetic resonance venography (MRV) scan. All of the patients had undergone angiographic examination. Four cases with membranous obstruction of the inferior vena cava (IVC) were treated with PTA. One case with segmental block of IVC was treated with PTA and stent placement. Five cases with membranous obstruction of IVC and hepatic vein (/and accessory hepatic vein) were treated with PTA. Among 8 cases with membranous obstruction of hepatic veins, 6 cases were treated with PTA and the others with PTA and stent placement. Among 4 cases with blocks of 3 hepatic veins (HVs), one was treated with PTA, one with PTA plus catheter thrombolysis plus PTA, one with PTA and stent placement and the other one was unsuccessful. Three cases with obstruction of HV and accessory HV (AHV) were treated with PTA. Totally, 24 patients were treated with interventional approach and followed up. RESULT: The procedure was successful in 24 patients. The involved veins (hepatic veins or IVC) were patented after interventional procedure. The pressure of hepatic vein was (42.1 +/- 4.2) cm H2O (37-50 cm H2O) (1 cm H2O = 0.098 kPa) before the interventional therapy, while it was (17.3 +/- 3.3) cm H2O (14-26 cm H2O) after it. The pressure of IVC was (30.6 +/- 2.9) cm H2O (26-36 cm H2O) before the interventional therapy, while it was (18.8 +/- 4.2) cm H2O (15-26 cm H2O) after it. The symptoms and signs vanished instantly after interventional procedure. There were no procedure-related complications. The rate of overall initial cure was 96%. The patients were followed up for a mean of 25.8 months (range 6 months to 8 years). Seven cases developed restenosis after first procedure. Five of them were treated with PTA, one with PTA plus catheter thrombolysis plus PTA, one with PTA and stent placement. All of the involved veins were patented again. Clinical symptoms were relieved. There were no procedure-related complications as well. CONCLUSION: The interventional procedure in children and adolescents with BCS is the same as in adults. Radiological therapeutic intervention is efficacious and safe in children and adolescents with BCS. PMID- 24225291 TI - [Risk factors of invasive fungal infections in patients admitted to non- hematological oncology department and pediatric intensive care unit]. AB - OBJECTIVE: To determine risk factors of invasive fungal infections (IFI) in patients admitted to non-hematological oncology department and pediatric intensive care unit (PICU), in order to improve diagnostic level of invasive fungal infections. METHOD: We retrospectively assessed 85 hospitalized pediatric patients with invasive fungal infections in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2007 to Nov.2012. All the cases were either from non-hematological oncology department or the PICU.We reviewed risk factors of invasive fungal infections. RESULT: Among 85 patients, 42 had invasive candida infection, 20 invasive aspergillus infection, 21 cryptococcus infection, 1 Histoplasma capsulatum infection and 1 Mucor mucedo infection.In the 42 patients with invasive candida infection, 5 were young infants, 3 had combined immunodeficiency, 1 cellular immunodeficiency, 25 secondary infection due to long term use of corticosteroids and/or combined use of more than 2 kinds of antibiotics with primary disease, 5 prior intestinal tract surgery or chronic diarrheal disease, 1 reflux gastritis.In the 20 patients with invasive aspergillosis infection, 10 patients had chronic granulomatous disease, 5 long term use of corticosteroids >= 1 month, 3 long term use of corticosteroids and combined use of more than 2 kinds of antibiotics, 2 had no apparent host factors.In the 21 patients with cryptococcus infection, 2 patients had used corticosteroids >= 1 month, 2 had immunodeficiency mainly for lack of antibodies, while others had no apparent host factors. The child with Mucor mucedo infection had diabetes mellitus. And the one with Histoplasma capsulatum infection had immunodeficiency. CONCLUSION: High risk factors for IFI in patients admitted to non-hematological oncology department and PICU are primary immunodeficiency disease and long term use of corticosteroids and/or long term combined use of more than 2 kinds of antibiotics. Besides, young infant is also a high risk factor for invasive candida infection. Most of the cryptococcus infections and certain aspergillosis had no obvious host factors. PMID- 24225292 TI - [Diversity analysis of biofilm bacteria on tracheal tubes removed from intubated neonates]. AB - OBJECTIVE: The catheter-related infections caused by mechanical ventilation have become a intractable clinical problem, and it is related to the formation of bacterial biofilm (BF) on the surface of the implanted material. The majority of natural biofilms are formed by multiple bacterial species. However, there always only one or limited species were detected on tracheal tubes removed from intubated neonates by using traditional methods including bacterium culture and antigen detection. The aims of this study were to observe the bacterial communities diversity of BF on endotracheal tube (ETT), and discuss the difference between traditional bacterium culture methods and the use of molecular biology techniques on the basis of denatured gradient gel electrophoresis (DGGE), to provide new ideas for clinical prevention, diagnosis and treatment of bacterial infections. METHOD: Thirty-five ETTs were obtained from 26 neonates on mechanical ventilator (from October 2012 to March 2013) in Department of Neonatology of Children's Hospital. Among the patients, 18 were boys and 8 girls, and 19 patients were < 37 weeks gestational age and 7 patients >= 37 weeks. DGGE profiling of 16S rDNA gene amplicons was used to assess the diversity of the bacterial population by using the software of quantity one. TA Cloning Kit and sequencing were used to investigate the distribution of bacteria and common dominant bacteria in ETT-BF. RESULT: The mean bands of 35 ETTs cases were 13.8 +/ 5.4 from 16S rDNA PCR-DGGE, and the mean Shanon-Wiener indexes was 2.42 +/- 0.38. The 16 ETTs were collected in different stages of diseases from the 7 patients. The indwelling days of 6/7 patients' ETTs increased, the Shanon-siener indexes were decreased. Among the 6 cases from different basic illnesses, and there were different Shanon-siener indexes. The result of molecular cloning and sequencing for 24 dominant bands showed that 35 cases (100%) contained Klebsiella SP., 28 cases (80%) had Pseudomonas SP., 27 cases (77%) had Streptococcus SP., and 32 cases (91%) had Uncultured bacterium, while more than 2 bacterial species were found in 34 cases (97%). 28/35 (80%) Klebsiella SP. and 22/27(82%) Streptococcus SP. were accompanied by Pseudomonas SP.. There were 22 positive results of sputum culture from 26 newborns, including 10 strains (45%) of Klebsiella pneumoniae, 2 strains (9%) of Acinetobacter baumannii, Enterobacter cloacae and non-cultured bacterium in each patient (5%), but only one bacterium isolated from every sputum. Eight sputum samples had normal flora only, corresponding to the ETTs on which Klebsiella and other bacterial genuses were found. CONCLUSION: The diversity of microbiota in BF on ETT was confirmed. 16S rDNA PCR-DGGE could produce a more complete picture of bacterial community than traditional bacterium culture method. Klebsiella, Pseudomonas and Streptococcus were common dominant bacteria in ETT-BF, and there might be interactions among them in the formation of BF. PMID- 24225293 TI - [Analysis of influencing factors of transient hypothyroxinemia and low T3 syndrome in premature infants]. AB - OBJECTIVE: To investigate the influencing factors of transient hypothyroxinemia (THT) and low T3 syndrome (LT3S) in premature infants. METHOD: We have studied 418 premature infants whose gestational age was between 26 and 36 weeks.Serum thyronine (T4), triiodothyronine (T3) and thyrotropin (TSH) of them were detected on the fourteenth day approximately after birth. The patients were divided according to their serum T4, T3 and TSH into 3 groups (transient hypothyroxinemia, low T3 syndrome and normal). Then 20 Perinatal factors which may be associated with THT and LT3S were collected. The factors were analyzed by using Chi-square test and Logistic regression. RESULT: Forty-nine infants were found suffering from THT, 35 infants suffering from LT3S, and 334 infants in normal group. The prevalence rate of THT was 11.7%, and the prevalence rate of LT3S was 8.4%. Among the 20 factors, the factors related to the incidence of THT were male gender (OR = 1.863, 95%CI 0.966-3.594), albumin (OR = 2.401, 95%CI 1.294-4.455), dopamine (OR = 3.295, 95%CI 1.110-9.783) and those related to the incidence of LT3S were male gender (OR = 2.592, 95%CI 1.171-5.736), gestational age <= 28 wk (OR = 3.503, 95%CI 1.275-9.627). CONCLUSION: Male gender, albumin and dopamine are perinatal risk factors of THT, meanwhile, male gender and gestational age <= 28 wk are perinatal risk factors of LT3S.With the use of risk factors identified in our study, it may be possible to separate infants having the highest risk of THT and LT3S, so as to form optimizing treatment strategies. PMID- 24225294 TI - [Expert's comment]. PMID- 24225295 TI - [Diagnostic value of amplitude-integrated electroencephalography in predicting outcome of newborn patients in neonatal intensive care unit]. AB - OBJECTIVE: To assess the diagnostic value of amplitude-integrated electroencephalography (aEEG) in predicting outcome of newborns who were at high risk for central nervous system without severe hypoxic-ischemic encephalopathy. METHODS: Forty-two consecutive patients at risks for neurological disorders referred to our level-III NICU were prospectively enrolled in the study over a period of 3 years. They were classified on the basis of their primary diagnoses including hypoglycemic brain damage, meningoencephalitis, bilirubin encephalopathy, and metabolic disease. Clinical data were collected. Amplitude integrated and raw EEG tracings were assessed for background pattern, sleep-wake cycling, and epileptiform activity. The neuromotor development of survivors was assessed by using the Infant Neurological International Battery (INFANIB). RESULT: The characteristic of aEEG tracings in 42 infants showed continuous normal voltage (CNV)(n = 15), discontinuous voltage (DC)(n = 9), burst suppression (BS) BS(+) (n = 6), BS(-)(n = 7), flat (FT, n = 5); mature sleep-wake cycling (SWC, n = 4), immature SWC (n = 14), no SWC (n = 24); 30 infants (71.4%) had electrical seizures: single seizure (n = 6); repetitive seizures (n = 7), and status epilepticus (SE) (n = 17).aEEG of 20 infants who had poor outcome showed FT (n = 5), BS(-)/SE (n = 6), BS(-)/ repetitive seizures (n = 1) , BS(+)/SE (n = 1), BS(+)/repetitive seizures (n = 1), DC/SE(n = 6). Chi-square analysis and Spearman rank correlation analysis showed the classification of aEEG background pattern, SWC and comprehensive score (score system was developed by evaluation of the above 3 variables) were correlated with the outcome of these infants at high neurological risks. CONCLUSION: Amplitude-integrated electroencephalography can provide important information of the status of cerebral function in neonates at high neurological risk and help to predict their outcome. PMID- 24225296 TI - [Clinical characteristics and imaging evaluation in children with renovascular hypertension]. AB - OBJECTIVE: To characterize the clinical and angiographic features in children with renovascular hypertension. METHOD: Clinical data of 14 children (7 male, 7 female; age 0.8-14 years, mean 8.7 years), who were diagnosed with renovascular hypertension by renal angiography in our institute from January 2005 to December 2012 were collected and retrospectively analyzed. RESULT: The mean blood pressure at the diagnosis was 187/127 mm Hg. Chief complaints of symptomatic patients were headache (29%, 4/14), hypertensive encephalopathy (36%, 5/14), signs of congestive heart failure (14%, 2/14) and hematemesis (7%, 1/14). Renovascular hypertension was found incidentally in 14% (2/14) of patients who were asymptomatic. Conventional renal angiography elucidated the anatomical distribution of lesions in the renal arterial system. It was found that 14% (2/14) of patients had bilateral disease, 50% (7/14) had single stenosis at main or accessory renal artery, while multiple stenoses was seen in 43% (6/14) of children, with involvement of segmental renal artery and small interlobar or arcuate vessels. Compared with catheter angiography, 50% (7/14) of patients with renovascular hypertension, especially intrarenal arterial disease, were missed on computed tomography angiography or magnetic resonance angiography. CONCLUSION: It is mandatory to emphasize blood pressure measurement in pediatric clinical practice for early recognition of renovascular hypertension. As children with renovascular hypertension display involvement of multiple arteries, including in smaller intrarenal arteries, digital subtraction angiography is the only method that can reliably diagnose pediatric renovascular hypertension. PMID- 24225297 TI - [Clinical features of a Chinese infant with inborn error of bile acid metabolism 3beta-hydroxy-Delta(5)-C27-steroid dehydrogenase deficiency and review of the literature]. AB - OBJECTIVE: To study the clinical features of children with 3beta-hydroxy-Delta(5) C27-steroid dehydrogenase deficiency and review the literature. METHOD: Clinical features and treatment of one Chinese infant with 3beta-hydroxy-Delta(5)-C27 steroid dehydrogenase deficiency confirmed by HSD3B7 gene mutation analysis were retrospectively reviewed, and 51 cases of 3beta-hydroxy-Delta(5)-C27-steroid dehydrogenase deficiency who were internationally reported since 2000 were also reviewed in this paper. RESULT: (1) A 3-month-old infant with neonatal cholestasis was admitted to our hospital because of hyperbilirubinemia and abnormal liver dysfunction (total bilirubin 110.7 umol/L, direct bilirubin 74.5 umol/L, gamma-glutamyltransferase 24.4 IU/L, total bile acid 0.1 umol/L).His jaundice disappeared within a few weeks, serum liver biochemistries improved and his growth in weight and height was excellent after oral cholic acid therapy.HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patient identified compound heterozygous mutations. This child was confirmed as the most common inborn error of bile acid metabolism-3beta-hydroxy-Delta(5)-C27 steroid dehydrogenase deficiency by molecular analysis.(2) Retrospective review of the literature showed that the clinical features of 3beta-hydroxy-Delta(5)-C27 steroid dehydrogenase deficiency included neonatal cholestasis, some patients progressed to severe liver disease and needed liver transplantation without effective therapy; however, serum biochemical characteristics of normal gamma glutamyltransferase activity, normal or low total bile acid concentrations were not consistent with cholestasis, the replacement treatment with cholic acid produced a dramatic improvements in symptoms, biochemical markers of liver injury; 31 cases were diagnosed by HSD3B7 gene mutation analysis. CONCLUSION: The clinical characteristics of 3beta-hydroxy-Delta(5)-C27-steroid dehydrogenase deficiency include neonatal cholestasis, normal serum gamma-glutamyltransferase activity, and normal or low serum total bile acid concentration.Oral cholic acid replacement is an effective therapy; definitive diagnosis of 3beta-hydroxy Delta(5)-C27-steroid dehydrogenase deficiency can be identified by molecular genetic testing technology. PMID- 24225298 TI - [Klinefelter syndrome complicated by mediastinal teratomas and precocious puberty: a case report]. PMID- 24225300 TI - [Spasmus nutans]. PMID- 24225299 TI - [Development of inhibitor against hemophilia and prevention and management strategies forpatients with hemophilia]. PMID- 24225301 TI - [Summary of the 12th national conference on pediatric endocrine, genetic and metabolic diseases]. PMID- 24225302 TI - A review on radiation-induced nucleation and growth of colloidal metallic nanoparticles. AB - This review presents an introduction to the synthesis of metallic nanoparticles by radiation-induced method, especially gamma irradiation. This method offers some benefits over the conventional methods because it provides fully reduced and highly pure nanoparticles free from by-products or chemical reducing agents, and is capable of controlling the particle size and structure. The nucleation and growth mechanism of metallic nanoparticles are also discussed. The competition between nucleation and growth process in the formation of nanoparticles can determine the size of nanoparticles which is influenced by certain parameters such as the choice of solvents and stabilizer, the precursor to stabilizer ratio, pH during synthesis, and absorbed dose. PMID- 24225303 TI - Optimal sampling designs for estimation of Plasmodium falciparum clearance rates in patients treated with artemisinin derivatives. AB - BACKGROUND: The emergence of Plasmodium falciparum resistance to artemisinins in Southeast Asia threatens the control of malaria worldwide. The pharmacodynamic hallmark of artemisinin derivatives is rapid parasite clearance (a short parasite half-life), therefore, the in vivo phenotype of slow clearance defines the reduced susceptibility to the drug. Measurement of parasite counts every six hours during the first three days after treatment have been recommended to measure the parasite clearance half-life, but it remains unclear whether simpler sampling intervals and frequencies might also be sufficient to reliably estimate this parameter. METHODS: A total of 2,746 parasite density-time profiles were selected from 13 clinical trials in Thailand, Cambodia, Mali, Vietnam, and Kenya. In these studies, parasite densities were measured every six hours until negative after treatment with an artemisinin derivative (alone or in combination with a partner drug). The WWARN Parasite Clearance Estimator (PCE) tool was used to estimate "reference" half-lives from these six-hourly measurements. The effect of four alternative sampling schedules on half-life estimation was investigated, and compared to the reference half-life (time zero, 6, 12, 24 (A1); zero, 6, 18, 24 (A2); zero, 12, 18, 24 (A3) or zero, 12, 24 (A4) hours and then every 12 hours). Statistical bootstrap methods were used to estimate the sampling distribution of half-lives for parasite populations with different geometric mean half-lives. A simulation study was performed to investigate a suite of 16 potential alternative schedules and half-life estimates generated by each of the schedules were compared to the "true" half-life. The candidate schedules in the simulation study included (among others) six-hourly sampling, schedule A1, schedule A4, and a convenience sampling schedule at six, seven, 24, 25, 48 and 49 hours. RESULTS: The median (range) parasite half-life for all clinical studies combined was 3.1 (0.7-12.9) hours. Schedule A1 consistently performed the best, and schedule A4 the worst, both for the individual patient estimates and for the populations generated with the bootstrapping algorithm. In both cases, the differences between the reference and alternative schedules decreased as half-life increased. In the simulation study, 24-hourly sampling performed the worst, and six-hourly sampling the best. The simulation study confirmed that more dense parasite sampling schedules are required to accurately estimate half-life for profiles with short half-life (<= three hours) and/or low initial parasite density (<= 10,000 per MUL). Among schedules in the simulation study with six or fewer measurements in the first 48 hours, a schedule with measurements at times (time windows) of 0 (0-2), 6 (4-8), 12 (10-14), 24 (22-26), 36 (34-36) and 48 (46-50) hours, or at times 6, 7 (two samples in time window 5-8), 24, 25 (two samples during time 23-26), and 48, 49 (two samples during time 47-50) hours, until negative most accurately estimated the "true" half-life. For a given schedule, continuing sampling after two days had little effect on the estimation of half life, provided that adequate sampling was performed in the first two days and the half-life was less than three hours. If the measured parasitaemia at two days exceeded 1,000 per MUL, continued sampling for at least once a day was needed for accurate half-life estimates. CONCLUSIONS: This study has revealed important insights on sampling schedules for accurate and reliable estimation of Plasmodium falciparum half-life following treatment with an artemisinin derivative (alone or in combination with a partner drug). Accurate measurement of short half-lives (rapid clearance) requires more dense sampling schedules (with more than twice daily sampling). A more intensive sampling schedule is, therefore, recommended in locations where P. falciparum susceptibility to artemisinins is not known and the necessary resources are available. Counting parasite density at six hours is important, and less frequent sampling is satisfactory for estimating long parasite half-lives in areas where artemisinin resistance is present. PMID- 24225304 TI - Report of a pertussis outbreak in a low coverage booster vaccination group of otherwise healthy children in Italy. AB - BACKGROUND: The introduction of universal pertussis immunization and the high coverage achieved in most developed countries have largely changed the epidemiology of the disease. Although vaccination rates are high in the first year of life, the rates of booster doses are unsatisfactory and lead to the onset of outbreaks. This report describes an outbreak of pertussis affecting school students already immunized in a town of Puglia (Italy), detected at the end of April 2009. METHODS: Vaccine effectiveness is measured by calculating the incidence rates (attack rates- AR) of disease among vaccinated (ARV) and unvaccinated (ARU) people and determining the percentage reduction in the incidence rate of disease among vaccinated people compared to unvaccinated people. RESULTS: The index case was a healthy child, female, 9-years-old who attended a local elementary school and developed pertussis on 27 April 2009. The secondary cases were the aunt and the cousin of the index case who developed a cough on 10 May 2009. In the elementary class of the index case, a cluster occurred. The overall AR was 15.8%, in particular 20% in children who did not receive the booster doses at 5-6 years old (ARU) and 14.3% in children receiving the booster (ARV). The VE of booster dose in this setting was 28.5%. Moreover, only the index case developed a persistent cough; the VE against moderate to severe pertussis was 100%. A cluster was detected in the middle school class that the cousin of the index case attended; AR was 44.4% (12/27); ARU was 50% (10/20) and ARV 28.6% (2/7). VE in this setting was 42.8%. CONCLUSIONS: Our results confirm the need to administer booster doses; failure the booster is the principal determinant for the outbreak onset. PMID- 24225305 TI - Impact of cardiac rehabilitation on renal function in patients with and without chronic kidney disease after acute myocardial infarction. AB - BACKGROUND: Although there is a general fear that exercise training might deteriorate renal function in chronic kidney disease (CKD) patients, the effect of cardiac rehabilitation (CR) on renal function in acute myocardial infarction (AMI) patients with CKD remains unknown. We sought to determine whether CR is associated with amelioration or deterioration of renal function in such patients. METHODS AND RESULTS: We enrolled 528 AMI patients who participated in a 3-month CR program. Clinical data before and after CR were compared according to participation in CR and comorbidities. In patients without CKD (estimated glomerular filtration rate [eGFR] >=60ml.min(-1).1.73m(-2), n=348), peak oxygen uptake (VO2) and B-type natriuretic peptide (BNP) improved without a change in eGFR. In contrast, in patients with CKD (eGFR <60ml.min(-1).1.73m(-2), n=180), eGFR improved (48+/-12 to 53+/-15ml.min(-1).1.73m(-2), P<0.001), together with improvements in peak VO2 and BNP. When patients with CKD were divided into non active (<=1time/week, n=70) and active participants (>=1.1time/week, n=110) according to attendance in CR, active participants showed an improvement in eGFR (50+/-10 to 53+/-13ml.min(-1).1.73m(-2), P<0.001), whereas eGFR did not change in non-active participants. Similar results were obtained in each subgroup of patients with hypertension, dyslipidemia, or diabetes mellitus. CONCLUSIONS: In AMI patients with CKD, active participation in CR was associated with improved peak VO2, BNP, and eGFR. PMID- 24225306 TI - Echolucency of carotid plaque is useful for assessment of residual cardiovascular risk in patients with chronic coronary artery disease who achieve LDL-C goals on statin therapy. AB - BACKGROUND: Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS: Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32+/-18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS: Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment. PMID- 24225307 TI - Incremental shuttle walk test as a valuable assessment of exercise performance in patients with pulmonary arterial hypertension. AB - BACKGROUND: Nearly all clinical trials investigating patients with pulmonary arterial hypertension (PAH) have used the 6-min walk test (6MWT) to evaluate exercise tolerance. The incremental shuttle walk test (SWT), however, has been proposed as a more valid and reproducible alternative to the 6MWT in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease. The efficacy of SWT in clinical practice to evaluate the exercise capacity of patients with PAH was investigated. METHODS AND RESULTS: The peak oxygen consumption (pVO2) and oxygen consumption at anaerobic threshold (VO2 at AT), the gold standard for measurement of exercise tolerance, 6MWT and SWT were measured in 19 clinically stable PAH patients (WHO functional class II-III) and the data compared. There was a higher correlation between SWT walk distance and pVO2 than between 6MWT walk distance and pVO2 (r=0.866 and 0.765, respectively; P<0.05), and a higher correlation between SWT walk distance and VO2 at AT than between 6MWT walk distance and VO2 at AT (r=0.775 and 0.587, respectively; P<0.05). No adverse events occurred during the exercise tests. CONCLUSIONS: SWT is a better reflection than 6MWT of exercise tolerance in PAH patients, and thus is a preferable alternative for assessment of exercise tolerance in PAH patients. PMID- 24225308 TI - Acute inactivation of the serine-threonine kinase Stk25 disrupts neuronal migration. AB - BACKGROUND: Neuronal migration involves the directional migration of immature neurons. During much of the migration period these neurons are polarized with defined leading and trailing processes. Stk25 has been shown to bind to the LKB1 activator STRAD and regulate neuronal polarization and dendritogenesis in an opposing manner to Reelin-Dab1 signaling. It is not known, however, whether Stk25 controls neuronal migration, a key developmental process regulated by Reelin-Dab1 signal transduction. FINDINGS: Here we find that while constitutive Stk25 deficiency does not lead to neuronal phenotypes, acute reduction by either Cre mediated gene inactivation or by knockdown causes a developmental neuronal migration error. Furthermore, we find that knockdown of LKB1, STRAD and GM130, molecules that have previously been implicated with Stk25, causes similar aberrations in neuronal migration. CONCLUSIONS: Loss of Stk25 function early in development likely leads to functional compensation for its roles in neuronal development. Stk25 regulates neuronal positioning, possibly as part of the LKB1 STRAD-Stk25-GM130 pathway that was previously shown to be important for neuronal polarization. PMID- 24225309 TI - New approach for fish breeding by chemical mutagenesis: establishment of TILLING method in fugu (Takifugu rubripes) with ENU mutagenesis. AB - BACKGROUND: In fish breeding, it is essential to discover and generate fish exhibiting an effective phenotype for the aquaculture industry, but screening for natural mutants by only depending on natural spontaneous mutations is limited. Presently, reverse genetics has become an important tool to generate mutants, which exhibit the phenotype caused by inactivation of a gene. TILLING (Targeting Induced Local Lesions IN Genomes) is a reverse genetics strategy that combines random chemical mutagenesis with high-throughput discovery technologies for screening the induced mutations in target genes. Although the chemical mutagenesis has been used widely in a variety of model species and also genetic breeding of microorganisms and crops, the application of the mutagenesis in fish breeding has been only rarely reported. RESULTS: In this study, we developed the TILLING method in fugu with ENU mutagenesis and high-resolution melting (HRM) analysis to detect base pair changes in target sequences. Fugu males were treated 3 times at weekly intervals with various ENU concentrations, and then the collected sperm after the treatment was used to fertilize normal female for generating the mutagenized population (F1). The fertilization and the hatching ratios were similar to those of the control and did not reveal a dose dependency of ENU. Genomic DNA from the harvested F1 offspring was used for the HRM analysis. To obtain a fish exhibiting a useful phenotype (e.g. high meat production and rapid growth), fugu myostatin (Mstn) gene was examined as a target gene, because it has been clarified that the mstn deficient medaka exhibited double-muscle phenotype in common with MSTN knockout mice and bovine MSTN mutant. As a result, ten types of ENU-induced mutations were identified including a nonsense mutation in the investigated region with HRM analysis. In addition, the average mutation frequency in fugu Mstn gene was 1 mutant per 297 kb, which is similar to values calculated for zebrafish and medaka TILLING libraries. CONCLUSIONS: These results demonstrate that the TILLING method in fugu was established. We anticipate that this TILLING approach can be used to generate a wide range of mutant alleles, and be applicable to many farmed fish that can be chemically mutagenized. PMID- 24225311 TI - The prevalence of fibromyalgia among patients with cervical radiculopathy due to cervical disc herniation: a pilot study. AB - BACKGROUND: Cervical disc herniation (CDH) is the most common cause of cervical radiculopathy and could overlap with fibromyalgia (FM). OBJECTIVE: The primary aim of the present study was to investigate the prevalences of FM and widespread pain in patients with cervical radiculopathy diagnosed as CDH in a cross sectional study. The secondary aim was to analyze the localization of tender points (TPs) and associated symptoms in these patients comparing patients with FM. METHODS: Fifty-two patients with cervical radiculopathy who carried the diagnosis of CDH and 51 patients with FM included to the study. The patients were questioned for the distribution and the duration of pain and for a group of symptoms related to FM such as headache, fatigue with a two-point scale (0 "no", 1 "yes"). The diagnosis of CDH was made with patients' clinical evaluation and radiological findings with Magnetic Resonans Imaging Study. FM was diagnosed using the American College of Rheumatology criteria. Widespread pain was defined as all of the following parameters were present: pain in the left side of the body; pain in the right side of the body; pain above the waist; pain below the waist; axial skeletal pain; and duration of pain for more than 3 months. The number of TPs were counted by digital palpation. RESULTS: Six female patients (11.5%) with CDH fulfilled the ACR 1990 criteria for FM. Of the patients with CDH 71.8% of TPs were located around the neck and shoulder regions, while 58.7% of TPs of the patients with FM were located around these regions. There were statistically significant differences between the patients with CDH and the patients with FM in terms of the duration of widespread pain, the number of TPs and the localization of TPs (p< 0.05). CONCLUSIONS: The prevalences of FM and widespread pain in patients with CDH were found as 11.5% and 78.8% respectively. PMID- 24225312 TI - Effects of thermal agents on electrical sensory threshold and current tolerance when applied prior to neuromuscular electrical stimulation. AB - BACKGROUND AND OBJECTIVE: This study aimed to investigate the effects of thermal agents on electrical sensory threshold and current tolerance when applied prior to neuromuscular electrical stimulation. METHODS: In this single-blind and cross over trial, electrical sensory threshold and current tolerance of 24 healthy volunteers were evaluated by using biphasic symmetrical pulses (240 MUsec, 50 pps), before and after thermal agent (cold pack, hot pack and ultrasound) applications. RESULTS: Electrical sensory threshold increased after cold-pack, and current tolerance reduced after hot-pack applications (p< 0.05). Inter-agent comparisons of pre and post-application differences of the investigated parameters revealed that the most obvious effects were caused by application of hot pack. CONCLUSIONS: Hot pack application prior to neuromuscular electrical stimulation (NMES) may reduce current tolerance and limit to reach the desired current intensity for strengthening the electrically induced contractions. Results are considered to be valuable for physiotherapists, who apply thermal agents and NMES consecutively, in their treatment programs. PMID- 24225313 TI - Paraoxonase 1 in neurological disorders. AB - Paroxonase 1 displays multiple physiological activities that position it as a putative player in the pathogenesis of neurological disorders. Here we reviewed the literature focusing on the role of paraoxonase 1 (PON1) as a factor in the risk of stroke and the major neurodegenerative diseases. PON1 activity is reduced in stroke patients, which significantly correlates inversely with carotid and cerebral atherosclerosis. The presence of the R allele of the Q192R PON1 polymorphism seems to potentiate this risk for stroke. PON1 exerts peroxidase activities that may be important in neurodegenerative disorders associated with oxidative stress. PON1 is also a key detoxifier of organophosphates and organophosphate exposure has been linked to the development of neurological disorders in which acetylcholine plays a significant role. In Parkinson's disease most of the studies suggest no participation of either L55M or the Q192R polymorphisms in its pathogenesis. However, many studies suggest that the MM55 PON1 genotype is associated with a higher risk for Parkinson's disease in individuals exposed to organophosphates. In Alzheimer's disease most studies have failed to find any association between PON1 polymorphisms and the development of the disease. Some studies show that PON1 activity is decreased in patients with Alzheimer's disease or other dementias, suggesting a possible protective role of PON1. No links between PON1 polymorphisms or activity have been found in other neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. PON1 is a potential player in the pathogenesis of several neurological disorders. More research is warranted to ascertain the precise pathogenic links and the prognostic value of its measurement in neurological patients. PMID- 24225314 TI - Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions. AB - Single-stranded DNA (ssDNA) plays a major role in several biological processes. It is therefore of fundamental interest to understand how the elastic response and the formation of secondary structures are modulated by the interplay between base pairing and electrostatic interactions. Here we measure force-extension curves (FECs) of ssDNA molecules in optical tweezers set up over two orders of magnitude of monovalent and divalent salt conditions, and obtain its elastic parameters by fitting the FECs to semiflexible models of polymers. For both monovalent and divalent salts, we find that the electrostatic contribution to the persistence length is proportional to the Debye screening length, varying as the inverse of the square root of cation concentration. The intrinsic persistence length is equal to 0.7 nm for both types of salts, and the effectivity of divalent cations in screening electrostatic interactions appears to be 100-fold as compared with monovalent salt, in line with what has been recently reported for single-stranded RNA. Finally, we propose an analysis of the FECs using a model that accounts for the effective thickness of the filament at low salt condition and a simple phenomenological description that quantifies the formation of non-specific secondary structure at low forces. PMID- 24225315 TI - The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. AB - The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37,000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states. PMID- 24225316 TI - Rapid metabolic pathway assembly and modification using serine integrase site specific recombination. AB - Synthetic biology requires effective methods to assemble DNA parts into devices and to modify these devices once made. Here we demonstrate a convenient rapid procedure for DNA fragment assembly using site-specific recombination by C31 integrase. Using six orthogonal attP/attB recombination site pairs with different overlap sequences, we can assemble up to five DNA fragments in a defined order and insert them into a plasmid vector in a single recombination reaction. C31 integrase-mediated assembly is highly efficient, allowing production of large libraries suitable for combinatorial gene assembly strategies. The resultant assemblies contain arrays of DNA cassettes separated by recombination sites, which can be used to manipulate the assembly by further recombination. We illustrate the utility of these procedures to (i) assemble functional metabolic pathways containing three, four or five genes; (ii) optimize productivity of two model metabolic pathways by combinatorial assembly with randomization of gene order or ribosome binding site strength; and (iii) modify an assembled metabolic pathway by gene replacement or addition. PMID- 24225317 TI - The transporter classification database. AB - The Transporter Classification Database (TCDB; http://www.tcdb.org) serves as a common reference point for transport protein research. The database contains more than 10,000 non-redundant proteins that represent all currently recognized families of transmembrane molecular transport systems. Proteins in TCDB are organized in a five level hierarchical system, where the first two levels are the class and subclass, the second two are the family and subfamily, and the last one is the transport system. Superfamilies that contain multiple families are included as hyperlinks to the five tier TC hierarchy. TCDB includes proteins from all types of living organisms and is the only transporter classification system that is both universal and recognized by the International Union of Biochemistry and Molecular Biology. It has been expanded by manual curation, contains extensive text descriptions providing structural, functional, mechanistic and evolutionary information, is supported by unique software and is interconnected to many other relevant databases. TCDB is of increasing usefulness to the international scientific community and can serve as a model for the expansion of database technologies. This manuscript describes an update of the database descriptions previously featured in NAR database issues. PMID- 24225318 TI - Selectome update: quality control and computational improvements to a database of positive selection. AB - Selectome (http://selectome.unil.ch/) is a database of positive selection, based on a branch-site likelihood test. This model estimates the number of nonsynonymous substitutions (dN) and synonymous substitutions (dS) to evaluate the variation in selective pressure (dN/dS ratio) over branches and over sites. Since the original release of Selectome, we have benchmarked and implemented a thorough quality control procedure on multiple sequence alignments, aiming to provide minimum false-positive results. We have also improved the computational efficiency of the branch-site test implementation, allowing larger data sets and more frequent updates. Release 6 of Selectome includes all gene trees from Ensembl for Primates and Glires, as well as a large set of vertebrate gene trees. A total of 6810 gene trees have some evidence of positive selection. Finally, the web interface has been improved to be more responsive and to facilitate searches and browsing. PMID- 24225319 TI - DNASU plasmid and PSI:Biology-Materials repositories: resources to accelerate biological research. AB - The mission of the DNASU Plasmid Repository is to accelerate research by providing high-quality, annotated plasmid samples and online plasmid resources to the research community through the curated DNASU database, website and repository (http://dnasu.asu.edu or http://dnasu.org). The collection includes plasmids from grant-funded, high-throughput cloning projects performed in our laboratory, plasmids from external researchers, and large collections from consortia such as the ORFeome Collaboration and the NIGMS-funded Protein Structure Initiative: Biology (PSI:Biology). Through DNASU, researchers can search for and access detailed information about each plasmid such as the full length gene insert sequence, vector information, associated publications, and links to external resources that provide additional protein annotations and experimental protocols. Plasmids can be requested directly through the DNASU website. DNASU and the PSI:Biology-Materials Repositories were previously described in the 2010 NAR Database Issue (Cormier, C.Y., Mohr, S.E., Zuo, D., Hu, Y., Rolfs, A., Kramer, J., Taycher, E., Kelley, F., Fiacco, M., Turnbull, G. et al. (2010) Protein Structure Initiative Material Repository: an open shared public resource of structural genomics plasmids for the biological community. Nucleic Acids Res., 38, D743-D749.). In this update we will describe the plasmid collection and highlight the new features in the website redesign, including new browse/search options, plasmid annotations and a dynamic vector mapping feature that was developed in collaboration with LabGenius. Overall, these plasmid resources continue to enable research with the goal of elucidating the role of proteins in both normal biological processes and disease. PMID- 24225320 TI - The Genome Database for Rosaceae (GDR): year 10 update. AB - The Genome Database for Rosaceae (GDR, http:/www.rosaceae.org), the long-standing central repository and data mining resource for Rosaceae research, has been enhanced with new genomic, genetic and breeding data, and improved functionality. Whole genome sequences of apple, peach and strawberry are available to browse or download with a range of annotations, including gene model predictions, aligned transcripts, repetitive elements, polymorphisms, mapped genetic markers, mapped NCBI Rosaceae genes, gene homologs and association of InterPro protein domains, GO terms and Kyoto Encyclopedia of Genes and Genomes pathway terms. Annotated sequences can be queried using search interfaces and visualized using GBrowse. New expressed sequence tag unigene sets are available for major genera, and Pathway data are available through FragariaCyc, AppleCyc and PeachCyc databases. Synteny among the three sequenced genomes can be viewed using GBrowse_Syn. New markers, genetic maps and extensively curated qualitative/Mendelian and quantitative trait loci are available. Phenotype and genotype data from breeding projects and genetic diversity projects are also included. Improved search pages are available for marker, trait locus, genetic diversity and publication data. New search tools for breeders enable selection comparison and assistance with breeding decision making. PMID- 24225321 TI - The genome portal of the Department of Energy Joint Genome Institute: 2014 updates. AB - The U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a national user facility, serves the diverse scientific community by providing integrated high throughput sequencing and computational analysis to enable system-based scientific approaches in support of DOE missions related to clean energy generation and environmental characterization. The JGI Genome Portal (http://genome.jgi.doe.gov) provides unified access to all JGI genomic databases and analytical tools. The JGI maintains extensive data management systems and specialized analytical capabilities to manage and interpret complex genomic data. A user can search, download and explore multiple data sets available for all DOE JGI sequencing projects including their status, assemblies and annotations of sequenced genomes. Here we describe major updates of the Genome Portal in the past 2 years with a specific emphasis on efficient handling of the rapidly growing amount of diverse genomic data accumulated in JGI. PMID- 24225322 TI - Progenetix: 12 years of oncogenomic data curation. AB - DNA copy number aberrations (CNAs) can be found in the majority of cancer genomes and are crucial for understanding the potential mechanisms underlying tumor initiation and progression. Since the first release in 2001, the Progenetix project (http://www.progenetix.org) has provided a reference resource dedicated to provide the most comprehensive collection of genome-wide CNA profiles. Reflecting the application of comparative genomic hybridization techniques to tens of thousands of cancer genomes, over the past 12 years our data curation efforts have resulted in a more than 60-fold increase in the number of cancer samples presented through Progenetix. In addition, new data exploration tools and visualization options have been added. In particular, the gene-specific CNA frequency analysis should facilitate the assignment of cancer genes to related cancer types. In addition, the new user file processing interface allows users to take advantage of the online tools, including various data representation options for proprietary data pre-publication. In this update article, we report recent improvements of the database in terms of content, user interface and online tools. PMID- 24225323 TI - PATRIC, the bacterial bioinformatics database and analysis resource. AB - The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10,000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue. PMID- 24225324 TI - Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes. AB - Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres. PMID- 24225325 TI - Efficacy of a nurse-led email reminder program for cardiovascular prevention risk reduction in hypertensive patients: a randomized controlled trial. AB - BACKGROUND: Many strategies have been evaluated to improve the prevention and control of cardiovascular (CVD) risk factors. Nursing telephonic and tele counseling individualized lifestyle educational programs have been found to improve blood pressure control and adherence to lifestyle recommendation. This study tested the efficacy of a nurse-led reminder program through email (NRP-e) to improve CVD risk factors among hypertensive adults. METHODS: All participants received usual CVD prevention and a guideline-based educational program. Subjects in the NRP-e group also received weekly email alerts and phone calls from a nurse care manager for 6 months. Emails contained a reminder program on the need for adherence with a healthy lifestyle based upon current guidelines. Follow-up visits were scheduled at 1, 3 and 6 months after enrollment; randomization was made centrally and blood samples were evaluated into a single laboratory. RESULTS: The final sample consisted of 98 (control) and 100 (NRP-e) subjects (mean age 59.0 +/- 14.5 years; 51.0% males). After 6 months, the following CVD risk factors significantly improved in both groups: body mass index, alcohol and fruit consumption, cigarette smoking, adherence to therapy hours, systolic and diastolic blood pressure, fasting blood glucose, low-density lipoproteins (LDL) and total cholesterol, triglycerides, and physical activity. In the NRP-e group, however, the prevalence of several behaviors or conditions at risk decreased significantly more than in the control group: obesity (-16%), low fruit consumption (-24%), uncontrolled hypertension (-61%), LDL (-56%), and total cholesterol (-40%). CONCLUSIONS: The NRP-e improved a range of CVD risk factors. The program had low costs, required only an average of <20 min per day in addition to normal practice, and may deserve further evaluation for the inclusion among existing care management approaches. PMID- 24225326 TI - Asteropsins B-D, sponge-derived knottins with potential utility as a novel scaffold for oral peptide drugs. AB - BACKGROUND: Known linear knottins are unsuitable as scaffolds for oral peptide drug due to their gastrointestinal instability. Herein, a new subclass of knottin peptides from Porifera is structurally described and characterized regarding their potential for oral peptide drug development. METHODS: Asteropsins B-D (ASPB, ASPC, and ASPD) were isolated from the marine sponge Asteropus sp. The tertiary structures of ASPB and ASPC were determined by solution NMR spectroscopy and that of ASPD by homology modeling. RESULTS: The isolated asteropsins B-D, together with the previously reported asteropsin A (ASPA), compose a new subclass of knottins that share a highly conserved structural framework and remarkable stability against the enzymes in gastrointestinal tract (chymotrypsin, elastase, pepsin, and trypsin) and human plasma. CONCLUSION: Asteropsins can be considered as promising peptide scaffolds for oral bioavailability. GENERAL SIGNIFICANCE: The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides. PMID- 24225327 TI - Eslicarbazepine acetate: an update on efficacy and safety in epilepsy. AB - Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. PMID- 24225329 TI - Physical independence and mortality at the extreme limit of life span: supercentenarians study in Japan. AB - BACKGROUND: Prevention of disability is a major challenge in aging populations; however, the extent to which physical independence can be maintained toward the limit of human life span remains to be determined. METHODS: We examined the health and functional status of 642 centenarians: 207 younger centenarians (age: 100-104 years), 351 semi-supercentenarians (age: 105-109 years), and 84 supercentenarians (age: >110 years). All-cause mortality was followed by means of an annual telephone or mailed survey. RESULTS: Age-specific disability patterns revealed that the older the age group, the higher the proportion of those manifesting independence in activities of daily living at any given age of entry. Multiple logistic regression analysis identified male gender and better cognitive function as consistent determinants of physical independence across all age categories. In a longitudinal analysis, better physical function was significantly associated with survival advantage until the age of 110. However, mortality beyond that age was predicted neither by functional status nor biomedical measurements, indicating alternative trajectories of mortality at the highest ages. CONCLUSIONS: These findings suggest that maintaining physical independence is a key feature of survival into extreme old age. Future studies illuminating genetic and environmental underpinnings of supercentenarians' phenotypes will provide invaluable opportunities not only to improve preventive strategies but also to test the central hypotheses of human aging. PMID- 24225328 TI - Seizure-induced disinhibition of the HPA axis increases seizure susceptibility. AB - Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility. PMID- 24225330 TI - Assessment of a nanocrystal 3-D morphology by the analysis of single HAADF-HRSTEM images. AB - This work presents the morphological characterization of CeO2 nanocrystals by the analysis of single unfiltered high-angle annular dark-field (HAADF)-high resolution scanning transmission electron microscopy (HRSTEM) images. The thickness of each individual atomic column is estimated by the classification of its HAADF integrated intensity using a Gaussian mixture model. The resulting thickness maps obtained from two example nanocrystals with distinct morphology were analyzed with aid of the symmetry from the CeO2 crystallographic structure, providing an approximation for their 3-D morphology with high spatial resolution. A confidence level of +/-1 atom per atomic column along the viewing direction on the thickness estimation is indicated by the use of multislice image simulation. The described characterization procedure stands out as a simple approach for retrieving morphological parameters of individual nanocrystals, such as volume and specific surface areas for different crystalline planes. The procedure is an alternative to the tilt-series tomography technique for a number of nanocrystalline systems, since its application does not require the acquisition of multiple images from the same nanocrystal along different zone axes. PMID- 24225331 TI - High-risk multiple myeloma: different definitions, different outcomes? AB - Multiple myeloma (MM) is a clonal plasma cell malignancy. Although MM is still not completely curable, it can be maintained at the level of a long-term chronic condition. Irrespective of the treatment strategy, relapse is still a major problem for most patients. Approximately 10% to 15% of all MM patients relapse early and have poor prognosis and outcome. Currently, there are many ways of identifying these high-risk patients using cytogenetics or molecular biology. Despite these various approaches to definition of high risk patients, a clear definition of high-risk MM has not been widely accepted. In this review, we discuss and compare various approaches, and their strengths and weaknesses in early identification of high-risk MM patients. PMID- 24225332 TI - Trial to examine text message-based mHealth in emergency department patients with diabetes (TExT-MED): a randomized controlled trial. AB - STUDY OBJECTIVE: Increasingly, low-income inner-city patients with diabetes utilize emergency departments (EDs) for acute and chronic care. We seek to determine whether a scalable, low-cost, unidirectional, text message-based mobile health intervention (TExT-MED) improves clinical outcomes, increases healthy behaviors, and decreases ED utilization in a safety net population. METHODS: We conducted an randomized controlled trial of 128 adult patients with poorly controlled diabetes (glycosylated hemoglobin [Hb A1C] level >=8%) in an urban, public ED. The TExT-MED group received 2 daily text messages for 6 months in English or Spanish. The primary outcome was change in Hb A1C level. Secondary outcomes included changes in medication adherence, self-efficacy, performance of self-care tasks, quality of life, diabetes-specific knowledge, ED utilization, and patient satisfaction. RESULTS: Hb A1C level decreased by 1.05% in the TExT MED group compared with 0.60% in the controls (Delta0.45; 95% confidence interval [CI] -0.27 to 1.17) at 6 months. Secondary outcomes favored the TExT-MED group, with the most sizable change observed in self-reported medication adherence (as measured by the Morisky Medication Adherence Scale, an 8-point validated scale with higher scores representing better adherence), which improved from 4.5 to 5.4 in the TExT-MED group compared with a net decrease of -0.1 in the controls (Delta1.1 [95% CI 0.1 to 2.1]). Effects were larger among Spanish speakers for both medication adherence (1.1 versus -0.3; Delta1.4; 95% CI 0.2 to 2.7) and Hb A1C (-1.2% versus -0.4%) in the TExT-MED group. The proportion of patients who used emergency services trended lower in the TExT-MED group (35.9% versus 51.6%; Delta15.7%; 95% CI 9.4% to 22%). Overall, 93.6% of respondents enjoyed TExT-MED and 100% would recommend it to family/friends. CONCLUSION: The TExT-MED program did not result in a statistically significant improvement in Hb A1C. However, trends toward improvement in the primary outcome of Hb A1C and other secondary outcomes, including quality of life, were observed, the most pronounced being improved medication adherence. TExT-MED also decreased ED utilization. These findings were magnified in the Spanish-speaking subgroup. Technologies such as TExT-MED represent highly scalable, low-cost, and widely accessible solutions for safety-net ED populations. PMID- 24225333 TI - A case of skeletal tuberculosis and psoas abscess: disease activity evaluated using (18) F-fluorodeoxyglucose positron emission tomography-computed tomography. AB - BACKGROUND: Psoas abscess complicating tuberculous spondylitis is a rare morbidity in extrapulmonary tuberculosis. There are no established guidelines for evaluating the clinical response of psoas abscess. Although several studies have shown that positron emission tomography-computed tomography with 18 F fluorodeoxyglucose can play a potential role in diagnosing multifocal tuberculosis and monitoring the clinical response of pulmonary tuberculosis, to our knowledge, this is the first report demonstrating that positron emission tomography-computed tomography is useful for evaluating local inflammation and disease activity of a tuberculous psoas abscess. CASE PRESENTATION: We report a case of multifocal bone and lymph node tuberculosis with concomitant lumbar psoas abscess in a 77-year-old man, along with a literature review. An initial positron emission tomography-computed tomography scan showed intense 18 F fluorodeoxyglucose accumulation in the sternum, ribs, vertebrae, and lymph nodes. The patient was successfully treated with antitubercular agents and computed tomography-guided drainage therapy. A follow-up positron emission tomography computed tomography after abscess drainage and 9 months of antitubercular drug treatment revealed that the majority of lesions improved; however, protracted inflammation surrounding the psoas abscess was still observed. These results indicate that disease activity of psoas abscess can remain, even after successful drainage and antitubercular medication regime of appropriate duration. CONCLUSION: We have successfully followed up the extent of skeletal tuberculosis complicated with psoas abscess by positron emission tomography-computed tomography. In this patient, positron emission tomography-computed tomography is useful for evaluating the disease activity of tuberculous psoas abscess and for assessing the appropriate duration of antitubercular drug therapy in psoas abscess. PMID- 24225334 TI - Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema: a prospective, multicentre, UK study. AB - OBJECTIVES: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. DESIGN: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. SETTING: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. PARTICIPANTS: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. INTERVENTIONS: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. MAIN OUTCOME MEASURES: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). RESULTS: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. CONCLUSIONS: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. STUDY REGISTRATION: This study has been registered as REC/IRAS 07/S0801/107, UKCRN ID 9063 and NIHR HTA 06/402/49. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 51. See the HTA programme website for further project information. PMID- 24225335 TI - Malaria in pregnancy in rural Gabon: a cross-sectional survey on the impact of seasonality in high-risk groups. AB - BACKGROUND: Malaria remains one of the most important infectious diseases in pregnancy in sub-Saharan Africa. Whereas seasonal malaria chemoprevention is advocated as public health intervention for children in certain areas of highly seasonal malaria transmission, the impact of seasonality on malaria in pregnancy has not yet been investigated for stable, hyper-endemic transmission settings of Equatorial Africa. The aim of this study was to investigate the influence of seasonality on the prevalence of malaria in pregnancy in Gabon. METHODS: The study was conducted at a rural district hospital in Gabon between January 2008 and December 2011. At first antenatal care visits demographic data, parity, age, and gestational age of pregnant women were documented and thick blood smears were performed for the diagnosis of malaria. Seasonality and established risk factors were evaluated in univariate and multivariate analysis for their association with Plasmodium falciparum infection. RESULTS: 1,661 pregnant women were enrolled in this study. Participants presenting during high transmission seasons were at significantly higher risk for P. falciparum infection compared to low transmission seasons (adjusted odds ratio [AOR] 1.91, 95% confidence interval [CI] 1.39-2.63, p < 0.001). Established risk factors including parity (AOR 0.45, CI 0.30-0.69, p < 0.001 for multipara versus paucipara) and age (AOR, CI and p value for women aged 13-17, 18-22, 23-27 and >= 28 years, respectively: AOR 0.59, CI 0.40-0.88; AOR 0.57, CI 0.34-0.97; AOR 0.51, CI 0.29-0.91) were significant risk factors for P. falciparum infection. High-risk groups including nulli- and primipara and younger women aged 13-17 years showed a disproportionately increased risk for malaria in high transmission seasons from 17% to 64% prevalence in low and high transmission periods, respectively. CONCLUSION: Seasonal variations lead to important differences in the risk for P. falciparum infection in pregnancy in the setting of central African regions with stable and hyper-endemic malaria transmission. The seasonal increase in malaria in pregnancy is most pronounced in high-risk groups constituted by young and pauciparous women. The evaluation of tailored seasonal prevention strategies for these high risk populations may, therefore, be warranted. PMID- 24225337 TI - Right ventricular reverse remodeling, but not subjective clinical amelioration, predicts long-term outcome after surgery for isolated severe tricuspid regurgitation. AB - BACKGROUND: Subjective clinical improvement does not always go hand-in-hand with right ventricular (RV) reverse remodeling after surgery for isolated severe tricuspid regurgitation (TR). This study aimed to evaluate the level of agreement between clinical improvement and echocardiographic RV reverse remodeling, and determine the relative prognostic powers of these 2 factors in terms of long-term prognosis for patients with isolated TR surgery. METHODS AND RESULTS: Sixty-one consecutive patients (58+/-8 years) were included. During a median follow up of 55 months (IQR, 36.5~71.5 months), a composite endpoint including death and admission for right heart failure was investigated. Extents of reductions in RV end-systolic area (RV-ESA) and subjective clinical improvement at 6 months were examined. There were 6 deaths and 5 admissions for right heart failure. A reduction in RV-ESA of >20% effectively predicted event-free survival, with a sensitivity of 90.9% and a specificity of 72.0% (AUC 0.81, P=0.001). With this cut-off, the agreement between a clinical and echocardiographic response was only 57.4% (35 patients). On Cox regression analysis, RV-ESA change emerged as the only independent predictor of event-free survival, whereas subjective clinical improvement did not. CONCLUSIONS: A discrepancy between subjective and echocardiographic improvement at 6 months after isolated TR surgery was observed in 42.6% of the patients. Echocardiographic RV reverse remodeling, but not subjective clinical amelioration, was a strong prognosticator after surgery. PMID- 24225338 TI - Comparison of effects of alpha-Glucosidase inhibitors and glinide drugs on endothelial dysfunction in diabetic patients with coronary artery disease. AB - BACKGROUND: Studies have shown that repeated post-prandial hyperglycemia may play an important role in the development of atherosclerosis by suppressing endothelial function. alpha-Glucosidase inhibitors (alpha-GIs), which reduce post prandial hyperglycemia without stimulating insulin secretion, significantly reduce the risk of coronary artery disease (CAD), whereas glinides, which improve post-prandial hyperglycemia through post-prandial insulin secretion, do not appear to affect CAD. METHODS AND RESULTS: A total of 104 diabetic patients with CAD were randomly divided into 2 groups: those treated with miglitol (M-group; n=52) and those treated with nateglinide (N-group; n=52). After 4 months' treatment, although hemoglobin A1c and 1,5-anhydroglucitol were significantly improved in both groups, only the M-group had significant reductions in insulin resistance index and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C; a beneficial index for assessing the presence of small dense low-density lipoprotein, and a marker of atherogenic dyslipidemia). Furthermore, only the M group had improvement in percentage flow-mediated dilatation (%FMD) and reactive oxygen metabolites. In the M-group, multiple regression analysis showed that improvement in TG/HDL-C, in addition to 1,5-anhydroglucitol, was an independent predictor of improvement in %FMD. CONCLUSIONS: The ameliorating effect of alpha GI on post-prandial hyperglycemia without stimulating insulin secretion may improve atherogenic dyslipidemia by reducing insulin resistance. These effects are associated with its beneficial impact on oxidative stress, consequently leading to an improvement in endothelial dysfunction. PMID- 24225339 TI - Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease. AB - Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease, and is now predominantly among patients with uncorrected left-to right shunts. A growing population is characterized by persistent or recurrent PAH after surgical or interventional correction of left-to-right shunts; the latter having a worse prognosis than other forms of PAH associated with congenital heart disease. New treatments for PAH have been shown to be effective in improving PAH exercise capacity and hemodynamics, raising the hope for making previously inoperable congenital heart defects operable and shifting the framework for the assessment of operability. This review focuses on current methods for assessing operability in PAH associated with congenital heart disease, and the possibility of "treat-and-repair" vs. "repair-and-treat" strategies for patients with inoperable or borderline PAH. PMID- 24225340 TI - Encephalopathy in children with Dravet syndrome is not a pure consequence of epilepsy. AB - BACKGROUND: Dravet syndrome (DS) is currently considered as an epileptic encephalopathy, a condition in which epilepsy causes deterioration or developmental delay but preliminary data suggested that cognitive course may worsen independently from epilepsy. Our objective was to prospectively analyze the neuropsychological features in a large cohort of DS patients and its relationships with epilepsy and SCN1A mutation. METHODS: 81 examinations were performed in 67 patients with typical DS (9m-24y, 15 longitudinally studied) using Brunet-Lezine (developmental/intelligence quotient [DQ/IQ] and DQ sub scores), Achenbach, Conners, and a semi-quantitative psychomotor score (SQPS). We studied the correlation between DQ/IQ/SQPS and age, epilepsy characteristics, and whether patients presented SCN1A mutation. RESULTS: DQ/IQ significantly decreased with age (r = -.53, p < .001), from normal before 2y (mean 80, range 64-105) to low after 3y (mean 48, range 30-69), with hyperactivity and attention disorders hampering learning abilities especially up to 6y. However, raw (not age-adjusted) DQ sub-scores increased with age during the first decade, showing that there is no regression. We did not find any significant correlation between DQ/IQ at last evaluation and epilepsy data, i.e. first seizure (age, type, duration, fever), seizures during the course (type, fever sensitivity), status epilepticus (age of onset, number, fever), photosensitivity, and treatment, except for myoclonus and focal seizures which were associated with a lower QD/IQ after 3y. SCN1A mutated patients (n = 58) seemed to exhibit worse psychomotor course than non-mutated ones (n = 9) (severe SQPS in 26% vs 0%), although their epilepsy tended to be less severe (tonic seizures in 12% vs 44% [p = 0.04], first status epilepticus before 6 m in 26% vs 67% [p = .02], mean number of SE 2.5 vs 4.5 [p = .09]). DQ sub-scores were dissociated throughout the whole course: from onset hand-eye coordination was significantly lower than language, posture and sociability (p < .01). Dissociation seemed to be more frequent in mutated than in non-mutated patients (motor SQPS was normal for in 77% vs 44% [p = 0.017] whereas language SQPS was normal for 47% vs 100%). CONCLUSIONS: Although psychomotor/cognitive delay declines with age, there is no regression. In addition, encephalopathy is not a pure consequence of epilepsy but SCN1A mutation seems to play an additional, direct role. PMID- 24225341 TI - Genomes of "Spiribacter", a streamlined, successful halophilic bacterium. AB - BACKGROUND: Thalassosaline waters produced by the concentration of seawater are widespread and common extreme aquatic habitats. Their salinity varies from that of sea water (ca. 3.5%) to saturation for NaCl (ca. 37%). Obviously the microbiota varies dramatically throughout this range. Recent metagenomic analysis of intermediate salinity waters (19%) indicated the presence of an abundant and yet undescribed gamma-proteobacterium. Two strains belonging to this group have been isolated from saltern ponds of intermediate salinity in two Spanish salterns and were named "Spiribacter". RESULTS: The genomes of two isolates of "Spiribacter" have been fully sequenced and assembled. The analysis of metagenomic datasets indicates that microbes of this genus are widespread worldwide in medium salinity habitats representing the first ecologically defined moderate halophile. The genomes indicate that the two isolates belong to different species within the same genus. Both genomes are streamlined with high coding densities, have few regulatory mechanisms and no motility or chemotactic behavior. Metabolically they are heterotrophs with a subgroup II xanthorhodopsin as an additional energy source when light is available. CONCLUSIONS: This is the first bacterium that has been proven by culture independent approaches to be prevalent in hypersaline habitats of intermediate salinity (half a way between the sea and NaCl saturation). Predictions from the proteome and analysis of transporter genes, together with a complete ectoine biosynthesis gene cluster are consistent with these microbes having the salt-out-organic-compatible solutes type of osmoregulation. All these features are also consistent with a well adapted fully planktonic microbe while other halophiles with more complex genomes such as Salinibacter ruber might have particle associated microniches. PMID- 24225342 TI - Lymphangiogenesis in canine mammary tumours: a morphometric and prognostic study. AB - Canine mammary tumours (CMTs) are the most common tumours of entire female dogs and represent a promising model for human breast cancer. Little is known about the presence and prognostic value of lymphangiogenesis in CMTs. The aims of the present study were to analyze selected characteristics of lymphatic vessels in CMTs, to evaluate their prognostic significance and to compare these results with studies of human breast cancer. Fifty-six benign CMTs, 55 malignant CMTs and 13 control samples of normal canine mammary gland tissue were studied. Serial immunohistochemical labelling with the lymphatic marker prox-1 and the proliferation marker Ki67 was performed. In intratumoural (IT) and peritumoural (PT) regions, the lymphatic vessel density (LVD), mean lymphatic vessel perimeter (LVP) and relative area occupied by lymphatic vessels (LVA) were analyzed. Lymphatic endothelial cell proliferation (LECP) and tumour cell proliferation (TCP) were also measured. Lymphatic vessels were identified in IT and PT regions and lymphangiogenesis was present in both regions. The IT lymphatic vessels were smaller, less numerous and occupied a smaller relative area compared with those of the PT region. Although no differences in lymphatic vessel parameters were observed between benign and malignant tumours, control tissue differed significantly from neoplastic tissue. None of the lymphatic vessel parameters showed a prognostic value, except for LECP in PT regions of benign tumours. The findings were in accordance with results of investigations into human breast cancer, which supports the use of dogs with spontaneously occurring CMTs as an animal model in comparative oncology trials. PMID- 24225343 TI - Are lopinavir and efavirenz serum concentrations in HIV-infected children in the therapeutic range in clinical practice? AB - BACKGROUND: In antiretroviral treatment the role of therapeutic drug monitoring via measurement of serum levels remains unclear, especially in children. AIM: To quantify exposure to LPV and EFV in children receiving therapy in a routine clinical setting in order to identify risk factors associated with inadequate drug exposure. METHOD: A prospective study was conducted in a routine clinical setting in Tygerberg Children's Hospital, South Africa. A total of 53 random serum levels were analyzed. Serum concentrations were determined by an established high-performance liquid chromatography method. RESULTS: Of 53 HIV infected children treated with lopinavir (n = 29, median age 1.83 y) or efavirenz (n = 24, median age 9.3 years), 12 showed serum levels outside the therapeutic range (efavirenz) or below Cmin (lopinavir). Low bodyweight, rifampicin co treatment, and significant comorbidity were potential risk factors for inadequate drug exposure. CONCLUSION: These findings, together with previous studies, indicate that therapeutic drug monitoring can improve the management of antiretroviral therapy in children at risk. PMID- 24225344 TI - Adsorption of Trametes versicolor laccase to soil iron and aluminum minerals: enzyme activity, kinetics and stability studies. AB - Laccases play an important role in the degradation of soil phenol or phenol-like substance and can be potentially used in soil remediation through immobilization. Iron and aluminum minerals can adsorb extracellular enzymes in soil environment. In the present study, we investigated the adsorptive interaction of laccase, from the white-rot fungus Trametes versicolor, with soil iron and aluminum minerals and characterized the properties of the enzyme after adsorption to minerals. Results showed that both soil iron and aluminum minerals adsorbed great amount of laccase, independent of the mineral specific surface areas. Adsorbed laccases retained 26-64% of the activity of the free enzyme. Compared to the free laccase, all adsorbed laccases showed higher Km values and lower Vmax values, indicating a reduced enzyme-substrate affinity and a lower rate of substrate conversion in reactions catalyzed by the adsorbed laccase. Adsorbed laccases exhibited increased catalytic activities compared to the free laccase at low pH, implying the suitable application of iron and aluminum mineral-adsorbed T. versicolor laccase in soil bioremediation, especially in acid soils. In terms of the thermal profiles, adsorbed laccases showed decreased thermal stability and higher temperature sensitivity relative to the free laccase. Moreover, adsorption improved the resistance of laccase to proteolysis and extended the lifespan of laccase. Our results implied that adsorbed T. versicolor laccase on soil iron and aluminum minerals had promising potential in soil remediation. PMID- 24225345 TI - Molecular memory with atomically smooth graphene contacts. AB - We report the use of bilayer graphene as an atomically smooth contact for nanoscale devices. A two-terminal bucky-ball (C60) based molecular memory is fabricated with bilayer graphene as a contact on the polycrystalline nickel electrode. Graphene provides an atomically smooth covering over an otherwise rough metal surface. The use of graphene additionally prohibits the electromigration of nickel into the C60 layer. The devices exhibit a low resistance state in the first sweep cycle and irreversibly switch to a high resistance state at 0.8 to 1.2 V bias. In the subsequent cycles, the devices retain the high-resistance state, thus making it write-once read-many memory. PMID- 24225346 TI - Conflict management styles, emotional intelligence and implicit theories of personality of nursing students: a cross-sectional study. AB - BACKGROUND: Conflict management is an essential skill that nursing students need to master as conflict is unavoidable in clinical settings. Examining nursing students' conflict management styles and the associating factors can inform nurse educators on how to equip nursing students for effective conflict management. OBJECTIVES: This study aimed at examining undergraduate nursing students conflict management styles in managing conflict with their supervisors in clinical placement. The associations of emotional intelligence and implicit theories of personality with conflict management styles were also investigated. DESIGN: This is a cross-sectional quantitative survey. SETTING: This study took place at a nursing school at a university in Hong Kong. PARTICIPANTS: 568 undergraduate nursing students participated in the study. METHODS: Students completed a questionnaire which consisted of demographics, Measure of Implicit Theories of Personality, The Schutte Emotional Intelligence Scale (SEIS) and The Rahim Organizational Conflict Inventory-II (ROCI-II) and received a HKD 20 book coupon as compensation. The data were analyzed by descriptive statistics, reliability analyses, t-tests, correlational and linear regression analyses. RESULTS: For managing conflict with clinical supervisors, students used obliging and integrating most frequently whereas used dominating least. Emotional intelligence was a significant predictor of all five conflict management styles. The higher the emotional intelligence, the more students used integrating, obliging, compromising and dominating. The lower the emotional intelligence, the more students used avoiding. There was a significant association between implicit theories of personality and compromising. The less malleable students perceived personality to be, the more they used compromising. CONCLUSIONS: Emotional intelligence was significantly associated with all five conflict management styles while implicit theories of personality were significantly associated with compromising style only. Efforts of nurse educators to enhance students' conflict management skills and emotional intelligence to face conflicts in clinical settings are discussed. PMID- 24225347 TI - Lipopolyplexes comprising imidazole/imidazolium lipophosphoramidate, histidinylated polyethyleneimine and siRNA as efficient formulation for siRNA transfection. AB - Lipopolyplexes formulations resulting from association of nucleic acid, cationic liposomes and a cationic polymer are attracting formulations for siRNA delivery. Herein, imidazole- and imidazolium-based liposomes in association with histidinylated polymers are studied to produce siRNA lipopoplyplexes (LPRi) subsequently used for gene silencing. Several kinds of imidazole/histidine liposomes and cationic polymers are tested. The gene silencing effect is evaluated with synthetic siRNA directed against EGFP or luciferase mRNA, in HeLa cells stably expressing EGFP or B16F10 melanoma cells stably expressing luciferase, respectively. SiRNA formulations are compared with those prepared using some commercial transfection reagents. One formulation called His-lPEI LPRi100 comprising siRNA, histidinylated lPEI (His-lPEI) and liposomes 100 made with O,O-dioleyl-N-[3N-(N-methylimidazolium iodide)propylene] phosphoramidate and O,O-dioleyl-N-histamine phosphoramidate appears to give the best specific inhibition of gene expression at 10nM siRNA in a dose-dependent manner with low cytotoxicity. This formulation exhibits a size and a zeta potential of 60 nm and +84 mV, respectively. According to our previous works, histidinylated lipopolyplexes appears as a versatile formulation for DNA, mRNA and siRNA transfection. PMID- 24225348 TI - Interventions for increasing ankle joint dorsiflexion: a systematic review and meta-analysis. AB - BACKGROUND: Ankle joint equinus, or restricted dorsiflexion range of motion (ROM), has been linked to a range of pathologies of relevance to clinical practitioners. This systematic review and meta-analysis investigated the effects of conservative interventions on ankle joint ROM in healthy individuals and athletic populations. METHODS: Keyword searches of Embase, Medline, Cochrane and CINAHL databases were performed with the final search being run in August 2013. Studies were eligible for inclusion if they assessed the effect of a non-surgical intervention on ankle joint dorsiflexion in healthy populations. Studies were quality rated using a standard quality assessment scale. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and results were pooled where study methods were homogenous. RESULTS: Twenty-three studies met eligibility criteria, with a total of 734 study participants. Results suggest that there is some evidence to support the efficacy of static stretching alone (SMDs: range 0.70 to 1.69) and static stretching in combination with ultrasound (SMDs: range 0.91 to 0.95), diathermy (SMD 1.12), diathermy and ice (SMD 1.16), heel raise exercises (SMDs: range 0.70 to 0.77), superficial moist heat (SMDs: range 0.65 to 0.84) and warm up (SMD 0.87) in improving ankle joint dorsiflexion ROM. CONCLUSIONS: Some evidence exists to support the efficacy of stretching alone and stretching in combination with other therapies in increasing ankle joint ROM in healthy individuals. There is a paucity of quality evidence to support the efficacy of other non-surgical interventions, thus further research in this area is warranted. PMID- 24225349 TI - A comparison of CKD-EPI estimated glomerular filtration rate and measured creatinine clearance in recently admitted critically ill patients with normal plasma creatinine concentrations. AB - BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) has been widely integrated into clinical practice. Although useful in screening for CKD, its' application in critically ill patients with normal plasma creatinine concentrations remains uncertain. The aim of this study was to assess the performance of CKD-EPI eGFR in comparison to creatinine clearance (CLCR) in this setting. METHODS: This prospective observational study was performed in a tertiary level, university affiliated intensive care unit (ICU). Study participants had to have an expected ICU length of stay > 24 hours, a plasma creatinine concentration < 121 MUmol/L, and no history of prior renal replacement therapy or CKD. CKD-EPI eGFR was compared against 8-hour measured urinary CLCR. Data capture occurred within 48 hours of admission. RESULTS: One hundred and ten patients (n = 110) were enrolled in the study. 63.6% were male, the mean age was 50.9 (16.9) years, 57.3% received invasive mechanical ventilation, and 30% required vasopressor support. The mean CLCR was 125 (45.1) ml/min/1.73 m(2), compared to a CKD-EPI eGFR of 101 (23.7) ml/min/1.73 m(2) (P < 0.001). Moderate correlation was evident (r = 0.72), although there was significant bias and imprecision (24.4 +/- 32.5 ml/min/1.73 m(2)). In those patients with a CKD-EPI eGFR between 60-119 ml/min/1.73 m(2) (n = 77), 41.6% displayed augmented renal clearance (CLCR >= 130 ml/min/1.73 m(2)), while 7.8% had a CLCR < 60 ml/min/1.73 m(2). CONCLUSIONS: These data suggest CKD EPI eGFR and measured CLCR produce significantly disparate results when estimating renal function in this population. Clinicians should consider carefully which value they employ in clinical practice, particularly drug dose modification. PMID- 24225350 TI - The HIV epidemic and human rights violations in Brazil. PMID- 24225351 TI - Low prevalence of the molecular markers of Plasmodium falciparum resistance to chloroquine and sulphadoxine/pyrimethamine in asymptomatic children in Northern Benin. AB - BACKGROUND: In Benin, very few studies have been done on the genetics of Plasmodium falciparum and the resistance markers of anti-malarial drugs, while malaria treatment policy changed in 2004. Chloroquine (CQ) and sulphadoxine pyrimethamine (SP) have been removed and replaced by artemisinin-combination therapy (ACT). The objective of this study was to determine the genetic diversity of P. falciparum and the prevalence of P. falciparum molecular markers that are associated with resistance to CQ and SP in northern Benin seven years after the new policy was instituted. METHODS: The study was conducted in northern Benin, a region characterized by a seasonal malaria transmission. Blood samples were collected in 2012 from children presenting with asymptomatic P. falciparum infections. Samples collected in filter paper were genotyped by primary and nested PCR in block 2 of msp-1 and block 3 of msp-2 to analyse the diversity of P. falciparum. The prevalence of critical point mutations in the genes of Pfcrt (codon 76), Pfmdr1 (codon 86), Pfdhfr (codons, 51, 59 and 108) and Pfdhps (codons 437, 540) was examined in parasite isolates by mutation-specific restriction enzyme digestion. RESULTS: Genotyping of 195 isolates from asymptomatic children showed 34 msp-1 and 38 msp-2 genotypes. The multiplicity of infection was 4.51 +/ 0.35 for msp-1 and 4.84 +/- 0.30 for msp-2. Only the codon 51 of Pfdhfr and codon 437 of Pfdhps showed a high mutation rate: I51: 64.4% (57.3; 71.2); G437: 47.4% (40.2; 54.7), respectively. The prevalence of Pfdhfr triple mutant IRN (I51, R59 and N108) was 1.5% (0.3; 3.9), and Pfdhfr/Pfdhps quadruple mutant IRNG (PfdhfrI51, R59, N108, and PfdhpsG437): 0. 5% (0; 2.5). No mutation was found with codon 540 of Pfdhps. Analysis of mutation according to age (younger or older than ten years) showed similar frequencies in each category without significant difference between the two groups. CONCLUSIONS: This study showed a high diversity of P. falciparum in northern Benin with a very low prevalence of resistance markers to CQ and SP that dramatically contrasted with the pattern observed in southern Benin. No influence of age on genetic diversity of P. falciparum and on distribution of the mutations was observed. PMID- 24225352 TI - Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults. AB - OBJECTIVE: The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including beta-amyloid 1-42 (Abeta1-42) and phosphorylated tau (P-tau) protein, in cognitively normal older adults. METHODS: One hundred seventy-seven cognitively normal, stroke-free older adult participants (aged 55-100 years) underwent blood pressure assessment for determination of PP (systolic - diastolic blood pressure) and lumbar puncture for measurement of CSF Abeta1-42 and P-tau. Pearson correlations and multiple linear regression, controlling for age, sex, APOE genotype, and body mass index, evaluated the relationship between PP and Alzheimer disease biomarkers. RESULTS: PP elevation was associated with increased P-tau (r = 0.23, p = 0.002), reduced Abeta1-42 (r = -0.19, p = 0.01), and increased P-tau to Abeta1-42 ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P tau (beta = 0.18, p = 0.0196) and P-tau to Abeta1-42 ratio (beta = 0.0016, p < 0.001) but was no longer associated with Abeta1-42 (beta = -0.1, p = 0.35). Post hoc multivariate analyses indicated that increased PP was associated with all biomarkers in younger participants (aged 55-70 years) (Abeta1-42: p = 0.050; P tau: p = 0.003; P-tau to Abeta ratio: p = 0.0007) but not older participants (aged 70-100 years). CONCLUSIONS: PP elevation is associated with increased CSF P tau and decreased Abeta1-42 in cognitively normal older adults, suggesting that pulsatile hemodynamics may be related to amyloidosis and tau-related neurodegeneration. The relationship between PP and CSF biomarkers is age dependent and observed only in participants in the fifth and sixth decades of life. PMID- 24225354 TI - A longitudinal study of weight gain in pregnancy in Malawi: unconditional and conditional standards. AB - BACKGROUND: To monitor weight gain during pregnancy and assess its relation with perinatal health outcomes, both unconditional (cross-sectional) and conditional (longitudinal) standards of maternal weight are needed. OBJECTIVE: This study aimed to develop and validate unconditional and conditional maternal weight standards for use in Malawi, Africa. DESIGN: Longitudinal data were drawn from an antenatal care intervention study conducted in Malawi. Participants were selected for this analysis if they had a healthy profile defined by body mass index and infectious disease measures and delivered healthy singletons defined by birth weight, gestational age, and neonatal survival status. A total of 1733 measurements from 358 women were randomly split to form development and validation samples. RESULTS: Unconditional and conditional standards were developed and validated. An electronic spreadsheet implements the calculations. Weight gain during pregnancy was substantially slower in this cohort than the US Institute of Medicine recommendation. The percentiles increased linearly; therefore, the use of the conditional standards is robust to inaccuracy in gestational age estimates. CONCLUSION: The standards can facilitate researchers and clinicians to examine maternal weight and weight gain and estimate their associations with pregnancy outcomes in Malawi. This trial was registered at www.clinicaltrials.gov as NCT00131235. PMID- 24225355 TI - Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study. AB - BACKGROUND: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change. OBJECTIVE: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk. DESIGN: This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association. RESULTS: A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. BMI at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found. CONCLUSIONS: BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women. PMID- 24225356 TI - Linear growth increased in young children in an urban slum of Haiti: a randomized controlled trial of a lipid-based nutrient supplement. AB - BACKGROUND: Haiti has experienced rapid urbanization that has exacerbated poverty and undernutrition in large slum areas. Stunting affects 1 in 5 young children. OBJECTIVE: We aimed to test the efficacy of a daily lipid-based nutrient supplement (LNS) for increased linear growth in young children. DESIGN: Healthy, singleton infants aged 6-11 mo (n = 589) were recruited from an urban slum of Cap Haitien and randomly assigned to receive: 1) a control; 2) a 3-mo LNS; or 3) a 6 mo LNS. The LNS provided 108 kcal and other nutrients including vitamin A, vitamin B-12, iron, and zinc at >=80% of the recommended amounts. Infants were followed monthly on growth, morbidity, and developmental outcomes over a 6-mo intervention period and at one additional time point 6 mo postintervention to assess sustained effects. The Bonferroni multiple comparisons test was applied, and generalized least-squares (GLS) regressions with mixed effects was used to examine impacts longitudinally. RESULTS: Baseline characteristics did not differ by trial arm except for a higher mean age in the 6-mo LNS group. GLS modeling showed LNS supplementation for 6 mo significantly increased the length-for-age z score (+/-SE) by 0.13 +/- 0.05 and the weight-for-age z score by 0.12 +/- 0.02 compared with in the control group after adjustment for child age (P < 0.001). The effects were sustained 6 mo postintervention. Morbidity and developmental outcomes did not differ by trial arm. CONCLUSION: A low-energy, fortified product improved the linear growth of young children in this urban setting. The trial was registered at clinicaltrials.gov as NCT01552512. PMID- 24225357 TI - Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials. AB - BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake. OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake. DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged >=18 y. For each biomarker response, the regression coefficient (beta) for individual studies and the overall pooled beta were calculated by using random-effects meta-analysis. RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 MUg/d. Calculation of the overall pooled beta for studies in the range of 50 to 400 MUg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate. CONCLUSIONS: Studies administering >400 MUg folic acid/d show no dose response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement. PMID- 24225358 TI - High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III. AB - BACKGROUND: Elevated serum phosphorus is associated with all-cause mortality, but little is known about risk associated with dietary phosphorus intake. OBJECTIVE: We investigated the association between phosphorus intake and mortality in a prospective cohort of healthy US adults (NHANES III; 1998-1994). DESIGN: Study participants were 9686 nonpregnant adults aged 20-80 y without diabetes, cancer, or kidney or cardiovascular disease. Exposure to dietary phosphorus, which was assessed by using a 24-h dietary recall, was expressed as the absolute intake and phosphorus density (phosphorus intake divided by energy intake). All-cause and cardiovascular mortality was assessed through 31 December 2006. RESULTS: Median phosphorus intake was 1166 mg/d (IQR: 823-1610 mg/d); median phosphorus density was 0.58 mg/kcal (0.48-0.70 mg/kcal). Individuals who consumed more phosphorus dense diets were older, were less often African American, and led healthier lifestyles (smoking, physical activity, and Healthy Eating Index). In analyses adjusted for demographics, cardiovascular risk factors, kidney function, and energy intake, higher phosphorus intake was associated with higher all-cause mortality in individuals who consumed >1400 mg/d [adjusted HR (95% CI): 2.23 (1.09, 4.5) per 1-unit increase in ln(phosphorus intake); P = 0.03]. At <1400 mg/d, there was no association. A similar association was seen between higher phosphorus density and all-cause mortality at a phosphorus density amount >0.35 mg/kcal [adjusted HR (95% CI): 2.27 (1.19, 4.33) per 0.1-mg/kcal increase in phosphorus density; P = 0.01]. At <0.35 mg/kcal (approximately the fifth percentile), lower phosphorus density was associated with increased mortality risk. Phosphorus density was associated with cardiovascular mortality [adjusted HR (95% CI): 3.39 (1.43, 8.02) per 0.1 mg/kcal at >0.35 mg/kcal; P = 0.01], whereas no association was shown in analyses with phosphorus intake. Results were similar by subgroups of diet quality and in analyses adjusted for sodium and saturated fat intakes. CONCLUSIONS: High phosphorus intake is associated with increased mortality in a healthy US population. Because of current patterns in phosphorus consumption in US adults, these findings may have important public health implications. PMID- 24225359 TI - Intake and serum concentrations of alpha-tocopherol in relation to fractures in elderly women and men: 2 cohort studies. AB - BACKGROUND: A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting. OBJECTIVE: The objective was to determine whether alpha-tocopherol intake or serum concentrations are associated with fracture risk in older women and men. DESIGN: Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used. RESULTS: During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of alpha-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). alpha-Tocopherol-containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of alpha-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1-4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum alpha-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48). CONCLUSION: Low intakes and low serum concentrations of alpha-tocopherol are associated with an increased rate of fracture in elderly women and men. PMID- 24225360 TI - Brain volumetric correlates of memory in early Parkinson's disease. AB - BACKGROUND: Free recall memory deficits are common in Parkinson's disease (PD), even at early stages before mild cognitive impairment or dementia. Their association with brain structural changes has not been established. OBJECTIVE: We studied local gray matter volumes in relation to different memory tasks in early stage PD. METHODS: Magnetic resonance images (MRI) and neuropsychological data were obtained from 28 non-demented, medicated PD patients, and 28 healthy controls. The gray matter segments of T1-weighted MRI images were analyzed using voxel-based morphometry in relation to visual and verbal memory tasks. Measures of immediate free recall, verbal learning, delayed recall and memory consolidation were obtained. A novel measure of incidental memory was included. RESULTS: Patients and controls showed no significant group differences in local gray matter volumes. Voxel-based morphometry analyses revealed that worse performance on an incidental visual memory task was associated with smaller right parietal gray matter volume (Family-wise error corrected P = 0.002). This association was present in the PD group (corrected P = 0.005), but not in controls (corrected P > 0.99). No associations between gray matter volumes and the other memory tasks were found in either group. CONCLUSIONS: The results suggest that right parietal cortical gray matter volume is related to free recall memory deficits in early stage PD in conditions not involving an intention to memorize visual items. This preliminary finding needs to be established in further studies utilizing incidental memory tasks in PD. PMID- 24225361 TI - The Gut Microbiotassay: a high-throughput qPCR approach combinable with next generation sequencing to study gut microbial diversity. AB - BACKGROUND: The intestinal microbiota is a complex and diverse ecosystem that plays a significant role in maintaining the health and well-being of the mammalian host. During the last decade focus has increased on the importance of intestinal bacteria. Several molecular methods can be applied to describe the composition of the microbiota. This study used a new approach, the Gut Microbiotassay: an assembly of 24 primer sets targeting the main phyla and taxonomically related subgroups of the intestinal microbiota, to be used with the high-throughput qPCR chip 'Access Array 48.48', AA48.48, (Fluidigm(r)) followed by next generation sequencing. Primers were designed if necessary and all primer sets were screened against DNA extracted from pure cultures of 15 representative bacterial species. Subsequently the setup was tested on DNA extracted from small and large intestinal content from piglets with and without diarrhoea. The PCR amplicons from the 2304 reaction chambers were harvested from the AA48.48, purified, and sequenced using 454-technology. RESULTS: The Gut Microbiotassay was able to detect significant differences in the quantity and composition of the microbiota according to gut sections and diarrhoeic status. 454-sequencing confirmed the specificity of the primer sets. Diarrhoea was associated with a reduced number of members from the genus Streptococcus, and in particular S. alactolyticus. CONCLUSION: The Gut Microbiotassay provides fast and affordable high-throughput quantification of the bacterial composition in many samples and enables further descriptive taxonomic information if combined with 454 sequencing. PMID- 24225363 TI - Screening for intestinal microflora influencing superoxide dismutase activity in mouse cecal mucosa. AB - We have suggested that intestinal microflora reduces the activity of the antioxidant enzyme superoxide dismutase (SOD) in the mouse cecal mucosa. In this study, gnotobiotic mice were used to examine the species of intestinal microflora influencing SOD activity in the cecal mucosa. The total SOD activity in the cecal mucosa of each germ-free (GF), gnotobiotic mouse with Escherichia coli, Lactobacillus and Bacteroides was significantly higher than that in the cecal mucosa of gnotobiotic mice with chloroform-treated feces (CHF), conventionalized (CVz) mice and conventional (CV) mice (P<0.05). In addition, CuZnSOD mRNA expression showed similar tendencies. Our results suggest that the antioxidant defense status in the cecal mucosa is influenced by CHF inoculation. PMID- 24225362 TI - Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. AB - BACKGROUND: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. METHODS: To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. RESULTS: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean +/- SE: 1.61 +/- 0.41) than in SCA2 (0.71 +/- 0.31), SCA3 (0.65 +/- 0.24) and SCA6 (0.87 +/- 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). CONCLUSIONS: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. PMID- 24225364 TI - 3-D aluminum nanostructure with microhole array synthesized by femtosecond laser radiation for enhanced light extinction. AB - This article presents 3-D aluminum micro-nanostructures for enhanced light absorption. Periodic microhole arrays were created by firing a train of femtosecond laser pulses at megahertz pulse frequency onto the surface of an aluminum target at ambient conditions. The laser trains ablated the target surface and created microholes leading to the generation of deposited nanostructures inside and around the microholes. These micro-nanostructures showed enhanced light absorption, which is attributed to surface plasmonics induced by the generation of both nano- and microstructures. These micro nanostructures may be promising for solar cell applications. PMID- 24225365 TI - Disc herniation in the thoracolumbar junction treated by minimally invasive transforaminal interbody fusion surgery. AB - Minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) has demonstrated efficacy in the treatment of lumbar degenerative diseases. Use of this procedure for thoracolumbar junction disc herniation remains challenging. Reports concerning MIS-TLIF at the thoracolumbar junction are rare. Thus, we performed a retrospective analysis of the clinical outcomes of 10 patients with thoracolumbar junction disc herniation treated by MIS-TLIF between December 2007 and October 2010. The purpose of this study was to investigate the efficacy and safety of MIS-TLIF for disc herniation in the thoracolumbar junction. Clinical and radiological data were collected and analyzed. Fusion levels included T12-L1 (two patients), L1-L2 (four patients) and L2-L3 (four patients). Clinical outcome was assessed using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). The average follow-up period was 39.2 months, with a minimum of 24 months. The mean +/- standard error of the mean of the operative time, intraoperative blood loss, and x-ray exposure were 128 +/- 36 minutes, 204 +/- 35 mL, and 43 +/- 12 seconds, respectively. The VAS for back and leg pain decreased significantly postoperatively from 6.4 +/- 2.7 to 1.5 +/- 0.6 (p<0.01), and from 7.1 +/- 2.4 to 1.3 +/- 0.4 (p<0.01) respectively, as did the ODI from 39.3 +/- 11.2 to 16.5 +/- 4.7 (p<0.01). Bone fusion was observed in eight patients. There were no other major complications at last follow-up. MIS-TIF is a safe and effective procedure for disc herniation in the thoracolumbar junction. Occurrence of non-union is relatively high compared to previous findings. PMID- 24225366 TI - Intact cell/intact spore mass spectrometry (IC/ISMS) on polymer-based, nano coated disposable targets. AB - Identification and differentiation of microorganisms has and still is a long arduous task, involving culturing of the organism in question on different growth media. This procedure, which is still commonly applied, is an established method, but takes a lot of time, up to several days or even longer. It has thus been a great achievement when other analytical tools like matrix-assisted laser desorption/ionization (MALDI) mass spectrometry were introduced for faster analysis based on the surface protein pattern. Differentiation and identification of human pathogens as well as plant/animal pathogens is of increasing importance in medical care (e.g. infection, sepsis, and antibiotics resistance), biotechnology, food sciences and detection of biological warfare agents. A distinction between microorganisms on the species and strain level was made by comparing peptide/protein profiles to patterns already stored in databases. These profiles and patterns were obtained from the surface of vegetative forms of microorganisms or even their spores by MALDI MS. Thus, an unknown sample can be compared against a database of known pathogens or microorganisms of interest. To benefit from newly available, metal-based disposable microscope-slide format MALDI targets that promise a clean and even surface at a fraction of the cost from full metal targets or MTP (microtiter plate) format targets, IC/ISMS analysis was performed on these and the data evaluated. Various types of bacteria as well as fungal spores were identified unambiguously on this disposable new type of metal nano-coated targets. The method even allowed differentiation between strains of the same species. The results were compared with those gained from using full metal standard targets and found to be equal or even better in several aspects, making the use of disposable MALDI targets a viable option for use in IC/ISMS, especially e.g. for large sample throughput and highly pathogenic species. PMID- 24225367 TI - High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency. AB - Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy. PMID- 24225368 TI - Proteolytic activity of Escherichia coli oligopeptidase B against proline-rich antimicrobial peptides. AB - Oligopeptidase B (OpdB) is a serine peptidase widespread among bacteria and protozoa that has emerged as a virulence factor despite its function has not yet been precisely established. By using an OpdB-overexpressing Escherichia coli strain, we found that the overexpressed peptidase makes the bacterial cells specifically less susceptible to several proline-rich antimicrobial peptides known to penetrate into the bacterial cytosol, and that its level of activity directly correlates with the degree of resistance. We established that E. coli OpdB can efficiently hydrolyze in vitro cationic antimicrobial peptides up to 30 residues in length, even though they contained several prolines, shortening them to inactive fragments. Two consecutive basic residues are a preferred cleavage site for the peptidase. In the case of a single basic residue, there is no cleavage if proline residues are present in the P1 and P2 positions. These results also indicate that cytosolic peptidases may cause resistance to antimicrobial peptides that have an intracellular mechanism of action, such as the proline-rich peptides, and may contribute to define the substrate specificity of the E. coli OpdB. PMID- 24225369 TI - Electricity generation by microbial fuel cell using microorganisms as catalyst in cathode. AB - The cathode reaction is one of the most seriously limiting factors in a microbial fuel cell (MFC). The critical dissolved oxygen (DO) concentration of a platinum loaded graphite electrode was reported as 2.2 mg/l, about 10-fold higher than an aerobic bacterium. A series of MFCs were run with the cathode compartment inoculated with activated sludge (biotic) or not (abiotic) on platinum-loaded or bare graphite electrodes. At the beginning of the operation, the current values from MFCs with a biocathode and abiotic cathode were 2.3 +/- 0.1 and 2.6 +/- 0.2 mA, respectively, at the air-saturated water supply in the cathode. The current from MFCs with an abiotic cathode did not change, but that of MFCs with a biotic cathode increased to 3.0 mA after 8 weeks. The coulomb efficiency was 59.6% in the MFCs with a biotic cathode, much higher than the value of 15.6% of the abiotic cathode. When the DO supply was reduced, the current from MFCs with an abiotic cathode decreased more sharply than in those with a biotic cathode. When the respiratory inhibitor azide was added to the catholyte, the current decreased in MFCs with a biotic cathode but did not change in MFCs with an abiotic cathode. The power density was higher in MFCs with a biotic cathode (430 W/m(3) cathode compartment) than the abiotic cathode MFC (257 W/m(3) cathode compartment). Electron microscopic observation revealed nanowire structures in biofilms that developed on both the anode and on the biocathode. These results show that an electron consuming bacterial consortium can be used as a cathode catalyst to improve the cathode reaction. PMID- 24225370 TI - Potential probiotic characterization of Lactobacillus plantarum strains isolated from Inner Mongolia "Hurood" cheese. AB - Total 121 lactic acid bacteria were isolated from homemade Inner Mongolia extra hard Hurood cheese. Seven of these strains, identified as Lactobacillus plantarum, were studied for probiotic characteristics. All seven strains survived at pH 3.0 for 3 h, or in the presence of oxgall at 0.3% or 0.6% for 4 h, but their viabilities were affected to different extents at pH 2.0 for 3 h. Strains C37 and C51 showed better adherence to Caco-2 cells, and higher hydrophobicity. The seven L. plantarum strains were different in in vitro free radical scavenging activities and cholesterolreducing ability. In vivo evaluation of the influence of L. plantarum C37 on the intestinal flora in a mouse model showed strain C37 could increase the viable counts of lactobacilli in feces of mice and decrease the viable counts of enterococci. When L. plantarum C37 was used to prepare probiotic Hurood cheese, it was able to maintain high viable counts (>7.8 log CFU/g) during the whole storage period, but the composition of the cheese was not changed. These results indicate that L. plantarum C37 could be considered as a promising probiotic strain. PMID- 24225371 TI - Design of quorum quenching microbial vessel to enhance cell viability for biofouling control in membrane bioreactor. AB - Quorum quenching (QQ) with a microbial vessel has recently been reported as an economically feasible biofouling control platform in a membrane bioreactor (MBR) for wastewater treatment. In this study, a quorum quenching MBR with a ceramic microbial vessel (CMV) was designed to overcome the extremely low F/M ratio inside a microbial vessel. The CMV was prepared with a monolithic ceramic microporous membrane and AHLdegrading QQ bacteria, Pseudomonas sp. 1A1. The "inner flow feeding mode" was introduced, under which fresh feed was supplied to the MBR only through the center lumen in the CMV. The inner flow feeding mode facilitated nutrient transport to QQ bacteria in the CMV and thus enabled relatively long-term maintenance of cell viability. The quorum quenching effect of the CMV on controlling membrane biofouling in the MBR was more pronounced with the inner flow feeding mode, which was identified by the slower increase in the transmembrane pressure as well as by the visual observation of a biocake that formed on the used membrane surface. In the QQ MBR with the CMV, the concentrations of extracellular polymeric substances were substantially decreased in the biocake on the membrane surface compared with those in the conventional MBR. The CMV also showed its potential with effective biofouling control over long-term operation of the QQ MBR. PMID- 24225372 TI - Optimization of extracellular production of recombinant human bone morphogenetic protein-7 (rhBMP-7) with Bacillus subtilis. AB - Extracellular production of recombinant human bone morphogenetic protein-7 (rhBMP 7) was carried out through the fermentation of Bacillus subtilis. Three significant fermentation conditions and medium components were selected and optimized to enhance the rhBMP-7 production by using the response surface methodology (RSM). The optimum values of the three variables for the maximum extracellular production of rhBMP-7 were found to be 2.93 g/l starch, 5.18 g/l lactose, and a fermentation time of 34.57 h. The statistical optimization model was validated with a few fermentations of B. subtilis in shake flasks under optimized and unoptimized conditions. A 3-L jar fermenter using the shake-flask optimized conditions resulted in a higher production (413 pg/ml of culture medium) of rhBMP-7 than in a shake flask (289.1 pg/ml), which could be attributed to the pH being controlled at 6.0 and constant agitation of 400 rpm with aeration of 1 vvm. PMID- 24225373 TI - Direct evaluation of the effect of gene dosage on secretion of protein from yeast Pichia pastoris by expressing EGFP. AB - Increasing the gene copy number has been commonly used to enhance the protein expression level in the yeast Pichia pastoris. However, this method has been shown to be effective up to a certain gene copy number, and a further increase of gene dosage can result in a decrease of expression level. Evidences indicate the gene dosage effect is product-dependent, which needs to be determined when expressing a new protein. Here, we describe a direct detection of the gene dosage effect on protein secretion through expressing the enhanced green fluorescent protein (EGFP) gene under the direction of the alpha-factor preprosequence in a panel of yeast clones carrying increasing copies of the EGFP gene (from one to six copies). Directly examined under fluorescence microscopy, we found relatively lower levels of EGFP were secreted into the culture medium at one copy and two copies, substantial improvement of secretion appeared at three copies, plateau happened at four and five copies, and an apparent decrease of secretion happened at six copies. The secretion of EGFP being limiting at four and five copies was due to abundant intracellular accumulation of proteins, observed from the fluorescence image of yeast and confirmed by western blotting, which significantly activated the unfolded protein response indicated by the up regulation of the BiP (the KAR2 gene product) and the protein disulfide isomerase. This study implies that tagging a reporter like GFP to a specific protein would facilitate a direct and rapid determination of the optimal gene copy number for high-yield expression. PMID- 24225374 TI - Screening of genes expressed in vivo during interaction between chicken and Campylobacter jejuni. AB - Chicken are considered as the most important source of human infection by Campylobacter jejuni, which primarily arises from contaminated poultry meats. However, the genes expressed in vivo of the interaction between chicken and C. jejuni have not been screened. In this regard, in vivo-induced antigen technology (IVIAT) was applied to identify expressed genes in vivo during interaction between chicken and C. jejuni, a prevalent foodborne pathogen worldwide. Chicken sera were obtained by inoculating C. jejuni NCTC 11168 into Leghorn chickens through oral and intramuscular administration. Pooled chicken sera, adsorbed against in vitrogrown cultures of C. jejuni, were used to screen the inducible expression library of genomic proteins from sequenced C. jejuni NCTC 11168. Finally, 28 unique genes expressed in vivo were successfully identified after secondary and tertiary screenings with IVIAT. The genes were implicated in metabolism, molecular biosynthesis, genetic information processing, transport, regulation and other processes, in addition to Cj0092, with unknown function. Several potential virulence-associated genes were found to be expressed in vivo, including chuA, flgS, cheA, rplA, and Cj0190c. We selected four genes with different functions to compare their expression levels in vivo and in vitro using real-time RT-PCR. The results indicated that these selected genes were significantly upregulated in vivo but not in vitro. In short, the expressed genes in vivo may act as potential virulence-associated genes, the protein encoded by which may be meaningful vaccine candidate antigens for campylobacteriosis. IVIAT provides an important and efficient strategy for understanding the interaction mechanisms between Campylobacter and hosts. PMID- 24225375 TI - Effects of iron-reducing bacteria on carbon steel corrosion induced by thermophilic sulfate-reducing consortia. AB - Four thermophilic bacterial species, including the iron-reducing bacterium Geobacillus sp. G2 and the sulfate-reducing bacterium Desulfotomaculum sp. SRB-M, were employed to integrate a bacterial consortium. A second consortium was integrated with the same bacteria, except for Geobacillus sp. G2. Carbon steel coupons were subjected to batch cultures of both consortia. The corrosion induced by the complete consortium was 10 times higher than that induced by the second consortium, and the ferrous ion concentration was consistently higher in iron reducing consortia. Scanning electronic microscopy analysis of the carbon steel surface showed mineral films colonized by bacteria. The complete consortium caused profuse fracturing of the mineral film, whereas the non-iron-reducing consortium did not generate fractures. These data show that the iron-reducing activity of Geobacillus sp. G2 promotes fracturing of mineral films, thereby increasing steel corrosion. PMID- 24225376 TI - Mini Nutritional Assessment and short-form Mini Nutritional Assessment can predict the future risk of falling in older adults - results of a national cohort study. AB - BACKGROUND & AIMS: Falling is a major issue in geriatric health. Tools that identify individuals at risk of falling can help reduce the risk of falling. The study aimed to determine whether the full and short-form Mini Nutritional Assessment (MNAs) have the ability to predict the risk of falling in older adults. METHODS: Subjects were 3118 >= 53-year old Taiwanese who completed both the 1999 and 2003 "Taiwan Longitudinal Study on Aging" surveys. We rated these subjects with normalized versions of the MNA and applied the standard cut-offs to define under-nutrition (<=23.5 and <=11 points, respectively). We used multivariate logistic regression analysis and receiver operating characteristics to evaluate the ability of these tools in predicting the risk of falling three years later. RESULTS: Older adults rated as at risk of malnutrition with the full MNA (OR = 1.87, 95% confidence interval = 1.33-2.63, p < 0.001) or the short-form (1.39, 1.07-1.80, p = 0.014) were associated with increased risk of falling three years later. Both versions significantly predicted the risk of falling and performed slightly better in >=65-year old persons than in younger (53-64-year old) persons. The short-form performed relatively well compared to the full scale. CONCLUSIONS: Results suggest that the full and short-form MNAs, in addition to rating the risk of malnutrition, also predict the risk of falling in older adults. Although the short-form is slightly less effective than the full scale in predicting the future risk of falling, its simplicity, effectiveness and efficiency make it ideal as a multipurpose screening tool in clinical settings. PMID- 24225377 TI - PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria. AB - BACKGROUND: The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC50) values to validate the trimodal distribution previously described and to validate the use of the pftetQ and pfmdt genes as molecular markers of decreased in vitro doxycycline susceptibility in Plasmodium falciparum malaria. METHODS: Doxycycline IC50 values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the different in vitro phenotypic groups by their IC50 values. Quantitative real-time polymerase chain reaction was used to evaluate the pftetQ and pfmdt copy numbers of 89 African P. falciparum isolates that were randomly chosen from the phenotypic groups. RESULTS: The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC50 was significantly higher in the group with a pftetQ copy number >1 compared to the group with a pftetQ copy number = 1 (33.17 MUM versus 17.23 MUM) and the group with a pfmdt copy number >1 (28.28 MUM versus 16.11 MUM). There was a significant difference between the combined low and medium doxycycline IC50 group and the high IC50 group in terms of the per cent of isolates with one or more copy numbers of the pftetQ gene (0% versus 20.69%) or pfmdt gene (8.33% versus 37.93%). In the logistic regression model, the pfmdt and pftetQ copy numbers >1 (odds ratio = 4.65 and 11.47) were independently associated with the high IC50 group. CONCLUSIONS: Copy numbers of pftetQ and pfmdt are potential predictive molecular markers of decreased susceptibility to doxycycline. PMID- 24225378 TI - Quantitative MRI analysis in children with multiple sclerosis: a multicenter feasibility pilot study. AB - BACKGROUND: Pediatric multiple sclerosis (MS) is a rare disorder with significant consequences. Quantitative MRI measurements may provide significant insights, however multicenter collaborative studies are needed given the small numbers of subjects. The goal of this study is to demonstrate feasibility and evaluate lesion volume (LV) characteristics in a multicenter cohort of children with MS. METHODS: A common MRI-scanning guideline was implemented at six member sites of the U.S. Network of Pediatric MS Centers of Excellence. We included in this study the first ten scans performed at each site on patients meeting the following inclusion criteria: pediatric RRMS within 3 years of disease onset, examination within 1 month of MRI and no steroids 1 month prior to MRI. We quantified T2 number, T2-LV and individual lesion size in a total of 53 MRIs passing quality control procedures and assessed gadolinium-enhancing lesion number and LV in 55 scans. We studied MRI measures according to demographic features including age, race, ethnicity and disability scores, controlling for disease duration and treatment duration using negative binomial regression and linear regression. RESULTS: The mean number of T2 lesions was 24.30 +/- 19.68 (range:1-113) and mean gadolinium-enhancing lesion count was 1.85 +/- 5.84, (range:0-32). Individual lesion size ranged from 14.31 to 55750.60 mm3. Non-white subjects had higher T2 LV (unadjusted pT2-LV = 0.028; adjusted pT2-LV = 0.044), and maximal individual T2-LV (unadjusted pMax = 0.007; adjusted pMax = 0.011) than white patients. We also found a trend toward larger mean lesion size in males than females (p = 0.07). CONCLUSION: Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS. PMID- 24225379 TI - Visual outcome of patients following NAION after treatment with adjunctive fluocortolone. AB - PURPOSE: Nonarteriitic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden loss of vision, which particularly affects individuals older than 50 years. Up to now there is no treatment that is effective at reversing or limiting the course of this disease. To study the short- and long-term effects of fluocortolone (FC) on the visual outcome of patients with acute NAION compared to standard treatment with pentoxifylline (PFX). METHODS: A prospective, quasirandomized intervention trial was conducted involving 60 patients with acute onset NAION. Patients in the comparison (PFX) group (n = 30) received PFX intravenously and per os for 7 days and then per os for a further 6 months, which is a standard treatment. Patients in the intervention (PFX + FC) group (n = 30) received the standard treatment plus 1 mg/kg FC for 5 days, with a subsequent stepwise dose reduction over time. As a primary outcome measure, the best corrected visual acuity (BCVA) was determined at the initial baseline consultation (i.e., before treatment), and at 3 days and 6 months after therapy onset. Visual field (VF) was analyzed using standard automated perimetry at the initial baseline examination and at 6 month after therapy onset. Changes in BCVA and visual field in the PFX and PFX + FC groups were compared and analyzed statistically. RESULTS: Treatment with FC resulted in a significant improvement in BCVA. Patients receiving FC in acute NAION were more likely to experience improvement and less likely to have worsened visual acuity (mean BCVA scores: at baseline, 0.22; after 3 days and 6 months of treatment, 0.33 and 0.43, respectively) than PFX patients (mean BCVA scores: at baseline, 0.33; after 3 days and 6 months of treatment, 0.33 and 0.28, respectively; p < 0.002 and 0.001). The beneficial effect was even more marked 6 months after therapy onset. Remarkably, patients with a baseline BCVA score of >=0.05 profited significantly by FC treatment (p < 0.006 and 0.001), whereas those with a baseline BCVA score of <0.05 did not (p < 0.4). PFX did not improve BCVA. However, VF did not show any significant improvement due to FC therapy. CONCLUSION: This is the first prospective randomized intervention trial that demonstrates the distinctive beneficial effects of FC in terms of the visual outcome of patients with NAION compared to standard treatment with only PFX. FC significantly improves both short- and long-term visual acuity in patients with moderate BCVA impairment due to recent onset of NAION, while VF did not show any significant improvement; however, PFX did neither enhance BCVA nor VF. Administration of FC should be seriously considered for the treatment of NAION whenever there are no contraindications. PMID- 24225381 TI - Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons. AB - PURPOSE OF REVIEW: The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field. RECENT FINDINGS: Several individual antiretroviral agents (ARVs) including tenofovir and several protease inhibitors have, in diverse study settings, been associated with renal impairment. Traditional renal risk factors are common among those experiencing adverse renal impairment to ARVs, but do not fully explain why only some develop these effects. Discontinuation of nephrotoxic ARVs is common with declining renal function, but has unknown long-term consequences. Immune suppression is a strong independent risk factor for renal impairment, and ongoing investigations will clarify whether initiating ARVs with nephrotoxic properties at higher CD4 cell counts will have net beneficial effects on renal function. SUMMARY: With improvements in survival, multiple risk factors have emerged for renal impairment in HIV-positive persons. Although certain ARVs may cause moderate renal impairment, effects on more severe renal impairment remain unresolved. Regular renal function monitoring allow for switching away from nephrotoxic ARVs in case of decreasing function. If such actions prove beneficial higher prevalence of ARV-associated severe renal impairment may emerge in populations without access to regular monitoring. PMID- 24225380 TI - Particle size and pathogenicity in the respiratory tract. AB - Particle size dictates where aerosolized pathogens deposit in the respiratory tract, thereafter the pathogens potential to cause disease is influenced by tissue tropism, clearance kinetics and the host immunological response. This interplay brings pathogens into contact with a range of tissues spanning the respiratory tract and associated anatomical structures. In animal models, differential deposition within the respiratory tract influences infection kinetics for numerous select agents. Greater numbers of pathogens are required to infect the upper (URT) compared with the lower respiratory tract (LRT), and in comparison the URT infections are protracted with reduced mortality. Pathogenesis in the URT is characterized by infection of the URT lymphoid tissues, cervical lymphadenopathy and septicemia, closely resembling reported human infections of the URT. The olfactory, gastrointestinal, and ophthalmic systems are also infected in a pathogen-dependent manner. The relevant literature is reviewed with respect to particle size and infection of the URT in animal models and humans. PMID- 24225383 TI - Does antiretroviral therapy started at high CD4 cell counts reduce an individual HIV-positive patient's disease risk? PMID- 24225382 TI - Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk. AB - PURPOSE OF REVIEW: To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk. RECENT FINDINGS: Factors leading to increased risk of non-AIDS-defining malignancies (NADMs) in particular remain poorly understood. Immunodeficiency appears to be key, whereas evidence is emerging that a direct pro-oncogenic effect of HIV, activated inflammatory and coagulation pathways, and cART toxicity may also contribute. By reducing HIV replication, improving immune function, and limiting chronic inflammation, cART initiation at higher CD4 cell counts may, therefore, reduce NADM risk. However, cART only partly normalizes enhanced inflammation and coagulation seen during HIV infection and conflicting laboratory and epidemiological data have been reported as to whether (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive. SUMMARY: Continuous epidemiological surveillance is warranted to monitor trends in cancer incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or antithrombotic therapies to reduce cancer risk deserves further investigation. PMID- 24225384 TI - Identification of novel transcripts and noncoding RNAs in bovine skin by deep next generation sequencing. AB - BACKGROUND: Deep RNA sequencing (RNAseq) has opened a new horizon for understanding global gene expression. The functional annotation of non-model mammalian genomes including bovines is still poor compared to that of human and mouse. This particularly applies to tissues without direct significance for milk and meat production, like skin, in spite of its multifunctional relevance for the individual. Thus, applying an RNAseq approach, we performed a whole transcriptome analysis of pigmented and nonpigmented bovine skin to describe the comprehensive transcript catalogue of this tissue. RESULTS: A total of 39,577 unique primary skin transcripts were mapped to the bovine reference genome assembly. The majority of the transcripts were mapped to known transcriptional units (65%). In addition to the reannotation of known genes, a substantial number (10,884) of unknown transcripts (UTs) were discovered, which had not previously been annotated. The classification of UTs was based on the prediction of their coding potential and comparative sequence analysis, subsequently followed by meticulous manual curation. The classification analysis and experimental validation of selected UTs confirmed that RNAseq data can be used to amend the annotation of known genes by providing evidence for additional exons, untranslated regions or splice variants, by approving genes predicted in silico and by identifying novel bovine loci. A large group of UTs (4,848) was predicted to potentially represent long noncoding RNA (lncRNA). Predominantly, potential lncRNAs mapped in intergenic chromosome regions (4,365) and therefore, were classified as potential intergenic lncRNA. Our analysis revealed that only about 6% of all UTs displayed interspecies conservation and discovered a variety of unknown transcripts without interspecies homology but specific expression in bovine skin. CONCLUSIONS: The results of our study demonstrate a complex transcript pattern for bovine skin and suggest a possible functional relevance of novel transcripts, including lncRNA, in the modulation of pigmentation processes. The results also indicate that the comprehensive identification and annotation of unknown transcripts from whole transcriptome analysis using RNAseq data remains a tremendous future challenge. PMID- 24225385 TI - Strain dependent neurochemical changes induced by embryonic alcohol exposure in zebrafish. AB - Fetal Alcohol Spectrum Disorder (FASD) is a preventable disease of the child resulting from alcohol (ethanol) consumption by pregnant women. Despite being preventable, FASD represents a prevalent problem throughout the world. Embryonic alcohol induced abnormalities in behavioral responses to social stimuli have been shown in humans and zebrafish. The neurobiological mechanisms underlying the abnormalities remain obscured. Here we start a mechanistic analysis by investigating the effect of embryonic alcohol exposure on the neurochemistry of zebrafish. The differing severity of symptoms seen in FASD may be partially due to genetic factors. To explore such genetic effects, here we analyzed two distinct zebrafish strains: AB and TU. Zebrafish were exposed to one of the following concentrations of alcohol, 0.00%, 0.25%, 0.50%, 0.75%, or 1.00% (vol/vol %) at 24 hours post-fertilization (hpf) for 2h. From whole brain extracts we analyzed the amount of neurotransmitters dopamine and serotonin and their metabolites across 4 different developmental time points: 15, 40, 70 and 102 days post-fertilization (dpf) using high performance liquid chromatography (HPLC). AB zebrafish exhibited a significant dose dependent embryonic alcohol exposure effect which increased in robustness with age. However, TU showed no such concentration effect: the levels of neurochemicals remained mainly unaltered by embryonic alcohol exposure in all age groups. We also analyzed the amount of alcohol reaching the embryo in the two strains and ruled out the possibility that TU has a more protective chorion. We conclude that the uncovered strain differences are due to genetic differences that protect TU from the deleterious effects of embryonic alcohol exposure. PMID- 24225386 TI - [COMMODE] a large-scale database of molecular descriptors using compounds from PubChem. AB - BACKGROUND: Molecular descriptors have been extensively used in the field of structure-oriented drug design and structural chemistry. They have been applied in QSPR and QSAR models to predict ADME-Tox properties, which specify essential features for drugs. Molecular descriptors capture chemical and structural information, but investigating their interpretation and meaning remains very challenging. RESULTS: This paper introduces a large-scale database of molecular descriptors called COMMODE containing more than 25 million compounds originated from PubChem. About 2500 DRAGON-descriptors have been calculated for all compounds and integrated into this database, which is accessible through a web interface at http://commode.i-med.ac.at. PMID- 24225387 TI - Moisture absorption early postmortem predicts ultimate drip loss in fresh pork. AB - Water-holding capacity is the ability of meat to hold moisture and is subject to postmortem metabolism. The objective of this study was to characterize the loss of moisture from muscle postmortem and investigate whether these losses are useful in predicting the ultimate drip loss of fresh pork. Cotton-rayon absorptive-based devices were inserted in the longissimus dorsi muscles of pork carcasses (n = 51) postmortem and removed at various intervals for 24h. Greatest moisture absorption was observed at 105 min post exsanguination. Drip loss varied (0.6-15.3%) across carcasses. Individual absorption at 75 min correlated (r = 0.33) with final drip loss. Correlations improved using individual absorption values at 90 min (r = 0.48) and accumulated absorption values at 150 min (r = 0.41). Results show that significant moisture is lost from muscle tissue early postmortem and suggest that capture of this moisture may be useful in predicting final drip loss of fresh meat. PMID- 24225388 TI - What are our moral duties? Critical reflections on clinical equipoise and publication ethics, clinical choices, and moral theory. PMID- 24225389 TI - The ethics of limiting informed debate: censorship of select medical publications in the interest of organ transplantation. AB - Recently, several articles in the scholarly literature on medical ethics proclaim the need for "responsible scholarship" in the debate over the proper criteria for death, in which "responsible scholarship" is defined in terms of support for current neurological criteria for death. In a recent article, James M. DuBois is concerned that academic critiques of current death criteria create unnecessary doubt about the moral acceptability of organ donation, which may affect the public's willingness to donate. Thus he calls for a closing of the debate on current death criteria and for journal editors to publish only critiques that "substantially engage and advance the debate." We argue that such positions as DuBois' are a threat to responsible scholarship in medical ethics, especially scholarship that opposes popular stances, because it erodes academic freedom and the necessity of debate on an issue that is literally a matter of life and death, no matter what side a person defends. PMID- 24225390 TI - Reproductive autonomy as self-making: procreative liberty and the practice of ethical subjectivity. AB - In this article, I consider recent debates on the notion of procreative liberty, to argue that reproductive freedom can be understood as a form of positive freedom-that is, the freedom to make oneself according to various ethical and aesthetic principles or values. To make this argument, I draw on Michel Foucault's later work on ethics. Both adopting and adapting Foucault's notion of ethics as a practice of the self and of liberty, I argue that reproductive autonomy requires enactment to gain meaning within the life contexts of prospective parents. Thus, I propose a shift away from the standard negative model of freedom that sees it solely as a matter of noninterference or nonimpedance, a view advocated by major commentators such as John Harris and John Robertson. Instead, reproduction should be understood as a deeply personal project of self-making that integrates both negative and positive freedom. PMID- 24225391 TI - "Comparable placebo treatment" and the ethics of deception. AB - Recent research, especially with functional brain imaging, demonstrated cases where the administration of a placebo produces objective effects in tissues that are indistinguishable from those of the real therapeutic agents. This phenomenon has been shown in treatments of pain, depression, Parkinsonism, and more. The main ethical complaint against placebo treatment is that it is a kind of deception, where supposedly we substitute what works just psychologically for a real drug that actually works on the tissue level. We claim that the scientific findings bring to a new level the seeming deconstruction of the distinction between "placebo" and "real" drugs, and that instances of placebo treatment which fulfill this criterion should be recognized as a unique category-we call it "comparable placebo treatment" (CPT). The paper uses an analysis of the notion of deception to argue that CPT does not amount to deception; that it can preserve patient autonomy; and that it is therefore morally legitimate. PMID- 24225396 TI - Blood-brain barrier impairment in MPS III patients. AB - BACKGROUND: Mucopolysaccharidosis type III (MPS III) is an autosomal recessive disorder caused by deficiency of a specific enzyme leading to heparan sulfate (HS) accumulation within cells and to eventual progressive cerebral and systemic organ abnormalities. Different enzyme deficiencies comprise the MPS III subcategories (A, B, C, D). Since neuropathological manifestations are common to all MPS III types, determining blood-brain barrier (BBB) condition may be critical to understand potential additional disease mechanisms. METHODS: We investigated BBB integrity in various brain structures of post-mortem tissues from an eleven year old Caucasian female with MPS III A and from a twenty four year old Caucasian female with MPS III D. Control tissues were obtained post mortem from three Caucasians without neurological deficits: a twelve year old male, a twenty four year old female, and a twenty seven year old female. BBB capillary ultrastructure (electron microscopy) and capillary functional integrity (IgG leakage, tight junction proteins, and lysosomal accumulation within endothelium) were examined. RESULTS: Compromised BBB integrity was found in both MPS III cases. Major study findings were: (1) capillary endothelial and pericyte cell damage; (2) mucopolysaccharide bodies in a majority of endothelial cells and pericytes rupturing cell membranes; (3) severe extracellular edema; (4) IgG microvascular leakage and reductions of occludin and claudin-5 with variations between MPS III types; (5) extensive lysosomal accumulation in capillary endothelium. CONCLUSIONS: These new findings of BBB structural and functional impairment, although from only two cases, MPS III A and III D, may have implications for disease pathogenesis and should be considered in treatment development for MPS III. PMID- 24225399 TI - Genetic factors associated with gemcitabine pharmacokinetics, disposition, and toxicity. AB - AIM: The goal of this work was to investigate the associations of genetic and environmental factors with gemcitabine disposition and toxicity from genomewide data using a novel information theoretic approach. METHODS: We utilized the information theoretic K-way interaction information (KWII) metric to detect gene gene and gene-environment interactions associated with gemcitabine disposition and gemcitabine-induced neutropenia in genomic and clinical data from Japanese cancer patients. RESULTS: The information theoretic KWII analyses identified age and four genes - DMD, HEXDC, CNTN4, and ALOX5AP - to be associated with gemcitabine pharmacokinetics (PK). The rs4769060 single-nucleotide polymorphism in the ALOX5AP gene was associated with all PK parameters studied. For gemcitabine-induced neutropenia, multiple associations with long intergenic noncoding RNA regions were detected. Pathway analysis identified leukotriene and eoxin synthesis, platelet homeostasis, and L1CAM interactions as potential pathways associated with gemcitabine disposition. CONCLUSION: The KWII analyses detected novel associations with gemcitabine PK and toxicity. These results could be used to inform future investigations involving gemcitabine efficacy in clinical settings. PMID- 24225400 TI - Spatial-temporal targeting of lung-specific mesenchyme by a Tbx4 enhancer. AB - BACKGROUND: Reciprocal interactions between lung mesenchymal and epithelial cells play essential roles in lung organogenesis and homeostasis. Although the molecular markers and related animal models that target lung epithelial cells are relatively well studied, molecular markers of lung mesenchymal cells and the genetic tools to target and/or manipulate gene expression in a lung mesenchyme specific manner are not available, which becomes a critical barrier to the study of lung mesenchymal biology and the related pulmonary diseases. RESULTS: We have identified a mouse Tbx4 gene enhancer that contains conserved DNA sequences across many vertebrate species with lung or lung-like gas exchange organ. We then generate a mouse line to express rtTA/LacZ under the control of the Tbx4 lung enhancer, and therefore a Tet-On inducible transgenic system to target lung mesenchymal cells at different developmental stages. By combining a Tbx4-rtTA driven Tet-On inducible Cre expression mouse line with a Cre reporter mouse line, the spatial-temporal patterns of Tbx4 lung enhancer targeted lung mesenchymal cells were defined. Pulmonary endothelial cells and vascular smooth muscle cells were targeted by the Tbx4-rtTA driver line prior to E11.5 and E15.5, respectively, while other subtypes of lung mesenchymal cells including airway smooth muscle cells, fibroblasts, pericytes could be targeted during the entire developmental stage. CONCLUSIONS: Developmental lung mesenchymal cells can be specifically marked by Tbx4 lung enhancer activity. With our newly created Tbx4 lung enhancer-driven Tet-On inducible system, lung mesenchymal cells can be specifically and differentially targeted in vivo for the first time by controlling the doxycycline induction time window. This novel system provides a unique tool to study lung mesenchymal cell lineages and gene functions in lung mesenchymal development, injury repair, and regeneration in mice. PMID- 24225401 TI - How do employment types and job stressors relate to occupational injury? A cross sectional investigation of employees in Japan. AB - OBJECTIVE: This study investigated whether 1) the risk of occupational injury differs among permanent employees and specific types of temporary workers, 2) the risk of occupational injury differs across different employment types depending on the degree of job stressors. STUDY DESIGN: A cross-sectional study design based on self-report survey data. METHODS: A total of 36,688 full-time workers (28,868 men and 7820 women; average age = 35.4) were surveyed by means of a self administered questionnaire. Employment types consisted of permanent employment and two forms of temporary employment: direct-hire and temporary work agent (TWA). Job characteristics including job demands, job control, and social support at work were measured. Occupational injury was measured by asking whether the participant had an injury on the job in the past 12 months that required a medical treatment. To investigate the relationships between employment types, job stressors, and occupational injury, hierarchical moderated logistic regression tests were conducted. RESULTS: High job demands (OR = 1.44) and low job control (OR = 1.21) were significantly associated with an increased risk of occupational injury, while controlling for demographic, life style, health, and occupational factors. In addition, direct-hires (OR = 1.85) and temporary agent workers (OR = 3.26) had a higher risk of occupational injury compared with permanent employees. However, the relationship between employment types and the risk of occupational injury depended on the levels of job demands and job control. Specifically, the magnitude of the relationship between job demands and the risk of occupational injury was substantially greater for temporary work agents than for permanent employees when they reported low levels of job control. Such an interaction effect between job demands and job control on the risk of occupational injury was not observed between permanent employees and direct-hire temporary workers. CONCLUSION: The current study indicated that temporary workers might be more vulnerable to occupational injury than permanent employees. High levels of job demands and low levels of job control might also add to temporary workers' risk of occupational injury, particularly for TWAs. PMID- 24225402 TI - Ginkgo biloba extract and ginkgolide antiarrhythmic potential by targeting hERG and ICa-L channel. AB - We investigated the effects of Ginkgo biloba extract (GBE) and ginkgolide (GLD) on human ether-a-go-go-related gene (hERG)-encoded K(+) channels and its underlying mechanisms in the hERG-HEK293 cell line by determining GBE- and GLD induced changes in action potential duration (APD), L-type calcium currents (ICa L), and the intracellular calcium concentration ([Ca(2+)]i) in guinea-pig ventricular myocytes. hERG currents, APD and ICa-L were recorded using the whole cell patch clamp technique, the [Ca(2+)]i was examined by an immunofluorescence experiment. In the present study, we found that a low concentration of GBE (0.005 mg/ml) increased hERG currents, but the high concentration of GBE (from 0.05 to 0.25 mg/ml) reduced hERG currents. GLD reduced hERG currents in a concentration dependent manner (from 0.005 to 0.25 mg/ml). Both GBE and GLD altered kinetics of the hERG channel. GBE accelerated the activation of hERG channels without changing the inactivation curve, but reduced the time constant of inactivation; GLD did not shift the activation or the inactivation curve, but only reduced the time constant of inactivation. Both GBE and GLD shortened the APD, inhibited the ICa-L currents, and decreased the [Ca(2+)]i in isolated guinea-pig ventricular myocytes. The results indicate that GBE and GLD can prevent ischemic arrhythmias and have an antiarrhythmic effect potential via inhibition of IKr and ICa-L currents. PMID- 24225403 TI - Pharmacological evidence that dopamine inhibits the cardioaccelerator sympathetic outflow via D2-like receptors in pithed rats. AB - It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D1/2-like receptors or even alpha2-adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D2-like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 MUg/kg?min, D1-like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 MUg/kg?min) or quinpirole (100 MUg/kg?min): i) remained unaltered after saline or the antagonists SCH-23390 (D1-like, 300 MUg/kg) and rauwolscine (alpha2 adrenoceptors, 300 MUg/kg); and ii) was significantly antagonized by raclopride (D2-like, 300 MUg/kg). These antagonists, at the above doses, failed to modify the sympathetically-induced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D2-like receptors but not D1-like receptors or alpha2-adrenoceptors. PMID- 24225405 TI - Endogenous gas formation of carbon dioxide used for wound flooding--an experimental study with implications regarding gas microembolism during cardiopulmonary bypass. AB - BACKGROUND: Gas microembolisation is an identified risk in cardiac surgery. Flooding the wound with carbon dioxide is a method proposed to reduce this problem. The high solubility of carbon dioxide is beneficial, but may also cause problems. The gas solubility diminishes at warming and endogenous bubbles are formed when cold blood saturated with carbon dioxide is returned by cardiotomy suction. METHODS: The release of endogenous gas was measured at high resolution in an experimental digital model. A medium (water or blood) was incubated and equilibrated with gas (100% carbon dioxide or air) at a low temperature (10 degrees C or 23 degrees C). The temperature was increased to 37 degrees C and the gas release was measured, at rest and at fluid motion. RESULTS: The amount of carbon dioxide released at warming was substantial for both water and blood (both p=0.005). The effect was more pronounced when the temperature differential increased (p=0.005). However, blood and water differed in these terms: with water, the release of carbon-dioxide started instantly at warming; with blood, carbon dioxide remained dissolved and was released at fluid motion. When blood was warmed from 10 degrees C to 37 degrees C, the gas release corresponded to 44.4% (40.6/46.5) of the medium volume (median with quartile range). CONCLUSION: Gas dissolved in a medium becomes released at warming, as confirmed here. Blood exposed to carbon dioxide became heavily oversaturated at warming, with the gas instantly released at fluid motion. The amount of contained gas increased with a higher temperature differential. Our study has relevance to wound flushing, using carbon dioxide, in cardiac surgery. The clinical consequences of these findings remain to be answered. PMID- 24225404 TI - Pediatric sepsis: important considerations for diagnosing and managing severe infections in infants, children, and adolescents. AB - Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child's age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID- 24225407 TI - Ergonomic laparoscopic spreader for infantile hypertrophic pyloric stenosis. AB - BACKGROUND: Laparoscopic pyloromyotomy (LP) for Infantile Hypertrophic Pyloric Stenosis (IHPS) is associated with an increased risk of mucosal tears or incomplete myotomy when compared with open myotomy. Keeping these risks in mind, a new ergonomically designed spreader for LP was developed and investigated in IHPS. METHODS: The new Pyloric Spreader was designed as a 3.5 mm instrument specifically for minimal access application taking into consideration the specific needs of LP. RESULTS: LP was performed using this spreader in 25 infants with IHPS during a 5-year period from 2006-2012. After incising the pylorus using an arthrotomy knife blade, the spreader could be inserted with ease in the pyloric muscle slit and permitted spreading of the pyloric muscle without any circular tears. The axial handle attached to the spreader enable a wide and controlled muscular spreading without mucosal injuries or incomplete spreads. Two infants underwent surgical revision due to recurrent vomiting; however no signs of incomplete myotomy were evident and the vomiting which subsequently subsided was attributed to the preoperative administration of Rotavirus vaccines in these infants. CONCLUSION: The newly designed Pyloric Spreader offers a new ergonomically designed instrument with a flat tip for easy placement in the pyloric muscle slit, broad instrument surface to avoid circular muscle tears, rounded tip edges to prevent mucosal injuries, wide spreading capability for optimal muscle spread and an axial handle for better hand ergonomic for LP in IHPS. PMID- 24225408 TI - Efficacy of kinesiology taping for recovery of dominant upper back pain in female sedentary worker having a rounded shoulder posture. AB - BACKGROUND: Sedentary workers are most prone to work-related musculoskeletal disorders. OBJECTIVE: We report the case of a female sedentary worker with rounded shoulder posture (RSP) whose dominant upper back pain decreased after correction of her RSP with kinesiology taping. METHODS: We applied kinesiology taping around the patient's upper back and shoulder for 1 month (six times per week, each session lasting approximately 16 h) without any other interventions. RESULTS: After kinesiology taping, the RSP decreased progressively and the dominant upper back pain gradually disappeared. The patient no longer complained of dominant upper back pain during desk work. CONCLUSION: We believe that kinesiology taping may be used to enable recovery from dominant upper back pain in female sedentary workers with RSP. PMID- 24225406 TI - Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania. AB - BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ susceptibility in Malawi, Kenya, Mozambique, and Tanzania based on the prevalence of wild types at codon 76 of the Pfcrt gene in indigenous P. falciparum populations. The current prevalence of this Pfcrt-76 CQ resistance marker from six regions of Tanzania mainland is hereby reported. METHODS: DNA extracted from filter-paper dried blood spots and rapid diagnostics kit strips collected from finger-prick blood were used to genotype the Pfcrt-76 resistance marker using PCR RFLP. Data from previously published studies were used to generate CQ susceptibility recovery trends using logistic regression model. RESULTS: Seven hundred and forty one (741) samples were genotyped. The current frequency of the CQ-susceptible Pfcrt-K76 was above 92% and did not differ between regions in Tanzania (chi(2) = 2.37; p = 0.795). The K76 allelic prevalence was between 85.7 and 93% in regions (chi(2) = 7.88, p = 0.163). The CQ resistance recovery trends showed regional variability that may be caused by differences in malaria transmission intensity, but overall the trends converge as the susceptibility levels in all regions approach >90%. CONCLUSIONS: CQ withdrawal in Tanzania has resulted into >90% recovery of susceptibility in ten years of withdrawal. These findings are in support of the search for CQ-based combination drugs as a possible future alternative to SP for IPTp in places where full recovery of CQ susceptibility will be evident. PMID- 24225409 TI - Amount of accidental flush by syringe pump due to inappropriate release of occluded intravenous line. AB - BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner. OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount. METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion(r) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured. RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p < 0.001). CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful. PMID- 24225410 TI - Detection of Pantoea agglomerans in hip prosthetic infection by sonication of the removed prosthesis: the first reported case. AB - Pantoea agglomerans is a rare isolate in orthopaedic patients. We describe the first case of an acute hip prosthetic joint infection (PJI) caused by Pantoea agglomerans. The microorganism was detected after sonication of the removed hip endoprosthesis. PMID- 24225411 TI - Disease surveillance among newly arriving refugees and immigrants--Electronic Disease Notification System, United States, 2009. AB - PROBLEM/CONDITION: Approximately 450,000 legal permanent immigrants and 75,000 refugees enter the United States annually after receiving required medical examinations by overseas panel physicians (physicians who follow the CDC medical screening guidelines provided to the U.S. Department of State). CDC has the regulatory responsibility for preventing the introduction, transmission, and spread of communicable diseases into the United States as well as for developing the guidelines, known as technical instructions, for the overseas medical examinations. Other conditions that are not infectious might preclude an immigrant or refugee from entering the United States and also are reported as part of the medical examination. After arrival in the United States, all refugees are recommended to obtain a medical assessment by a health-care provider or a health department within 30 days. In addition, immigrants with certain medical conditions such as noninfectious tuberculosis at the time of the original medical examination are recommended to be evaluated after arrival to ensure that appropriate prevention or treatment measures are instituted. Health departments need timely and accurate notifications of newly arriving immigrants, refugees, and persons with other visa types to facilitate these evaluations. Notifications for all newly arriving refugees (with or without medical conditions) and immigrants with medical conditions are provided by CDC's Electronic Disease Notification (EDN) system. This is the first report describing EDN. REPORTING PERIOD: This report summarizes notifications by the EDN system during January December 2009. DESCRIPTION OF SYSTEM: The EDN system is a centralized electronic reporting system that collects health information on newly arriving refugees and immigrants with Class A and Class B medical conditions. Class A conditions render applicants inadmissible and require a waiver for entry; Class B conditions are admissible but might require treatment or follow-up. Information in the EDN system is used to notify state health departments in all 50 states and the District of Columbia about the arrival of these persons in the United States. RESULTS: In 2009, the EDN system notified U.S. state and local health departments of 104,954 newly arriving refugees and immigrants, of whom 78,899 (75.2%) were refugees (with or without medical conditions), 19,358 (18.4%) were immigrants with medical conditions, and 6,697 (6.4%) were persons with other visa types. Of the 78,899 refugees, 21,319 (27%) had a medical condition. The majority (93.4%) of immigrants with medical conditions had tuberculosis classifications (i.e., either had evidence of latent tuberculosis infection or chest radiograph findings interpreted by the overseas panel physician as consistent with tuberculosis). Of the 41,415 refugees and immigrants with Class A or Class B medical conditions, 405 (1%) had Class A conditions, and 40,994 (99%) had Class B conditions. The majority of refugees and immigrants with suspected Class B tuberculosis were born in the Philippines (41.3%), Mexico (12.1%), Burma (8.7%), Vietnam (7.8%), and the Dominican Republic (5.8%). The majority of refugee notifications were for persons born in Iraq (23.9%), Burma (18.9%), and Bhutan (15.1%). Approximately one third of the tuberculosis notifications were sent to health departments in California (20.5%), Texas (9.8%), and New York (6.3%), and the national reporting rate for tuberculosis follow-up was 75.4% within 30 days of arrival. INTERPRETATION: The findings in this report suggest that 1) overseas medical screening results in a low frequency (0.4%) of inadmissible medical conditions in the United States, 2) the EDN system provides more direct notifications to health departments than the previous paper-based system about newly arriving immigrants and refugees who need medical follow-up, and 3) approximately 75% of follow-up occurs among persons with suspected tuberculosis who are reported to EDN by states receiving newly arriving refugees and immigrants. PUBLIC HEALTH ACTIONS: The data in this report can be used to help state and local health departments provide prompt and effective follow-up, evaluation, and treatment to newly arriving immigrants and refugees. Timely follow-up might prevent additional spread of tuberculosis or other communicable diseases of public health significance into their communities. In addition, information from the EDN system allows health departments to use their resources as effectively as possible by providing clinical information that identifies the refugees and immigrants who should be prioritized for evaluation and treatment. PMID- 24225412 TI - Ballistic-like supercurrent in suspended graphene Josephson weak links. AB - The interplay of the massless Dirac fermions in graphene and the Cooper pair states in a superconductor has the potential to give rise to exotic physical phenomena and useful device applications. But to date, the junctions formed between graphene and superconductors on conventional substrates have been highly disordered. Charge scattering and potential fluctuations caused by such disorder are believed to have prevented the emergence or observation of new physics. Here we propose to address this problem by forming suspended graphene-superconductor junctions. We demonstrate the fabrication of high-quality suspended monolayer graphene-NbN Josephson junctions with device mobility in excess of 150,000 cm(2) per Vs, minimum carrier density below 10(10) cm(-2), and the flow of a supercurrent at critical temperatures greater than 2 K. The characteristics of our Josephson junctions are consistent with ballistic transport, with a linear dependence on the Fermi energy that reflects of linear dispersion of massless Dirac fermions. PMID- 24225413 TI - Targeting the heat shock protein 90: a rational way to inhibit macrophage migration inhibitory factor function in cancer. AB - PURPOSE OF REVIEW: Macrophage migration inhibitory factor (MIF), originally identified as a proinflammatory cytokine, is highly elevated in many human cancer types, independent of their histological origin. MIF's tumour promoting activities correlate with tumour aggressiveness and poor clinical prognosis. Genetic depletion of MIF in mouse cancer models results in significant inhibition of cell proliferation and induction of apoptosis, making it an attractive target for anticancer therapies. Here, we summarize the current possibilities to inhibit MIF function in cancer. RECENT FINDINGS: All known small molecule MIF inhibitors antagonize MIF's enzymatic function. However, a recent knockin mouse model suggested that protein interactions play a bigger biological role in tumour cell growth regulation than MIF's enzymatic activity. Thus, alternative strategies are important for targeting MIF. Recently, we identified that MIF in cancer cells is highly stabilized through the heat shock protein 90 machinery (HSP90). Thus, MIF is an HSP90 client. Pharmacological inhibition of the Hsp90 ATPase activity results in MIF degradation in several types of cancer cells. This provides a new way to inhibit MIF function independent of its enzymatic activity. SUMMARY: Targeting the HSP90 machinery is a promising way to inhibit MIF function in cancer. Along with MIF and dependent on the molecular make-up of the tumour, a large number of other critical tumourigenic proteins are also destabilized by HSP90 inhibition, overall resulting in a profound block of tumour growth. PMID- 24225414 TI - Appropriate dosing of adjuvant radioactive iodine for differentiated thyroid cancer. AB - PURPOSE OF REVIEW: The incidence of well differentiated thyroid cancer (WDTC) is increasing in the US population and is now a major public health concern. Although surgery is the mainstay of treatment, radioactive iodine (RAI) is routinely used for adjuvant therapy, remnant ablation, and for the treatment of metastatic disease. Despite excellent prognosis and stable mortality rates, the use of RAI is increasing in many low and intermediate risk WDTC patients without clear indication that it changes the outcome. As a result, the current treatment paradigm has shifted towards a risk-stratified approach. RECENT FINDINGS: Although there is widespread acceptance that RAI improves overall and recurrence free survival in patients with metastatic disease, controversy remains regarding radioactive remnant ablation use in low and intermediate risk patients. Additional studies have shown that reduced doses of RAI can provide similar rates of remnant ablation and adjuvant therapy in low and intermediate risk patients without adversely affecting the recurrence rates and mortality. SUMMARY: Recent studies suggest potential new paradigms in radioactive remnant ablation dosing and indications for use. Risk stratification is important in determining the proper use and dosing of RAI. PMID- 24225415 TI - Indications for the use of external beam radiation in thyroid cancer. AB - PURPOSE OF REVIEW: The role of external beam radiation therapy (EBRT) in the management of thyroid cancer is not clearly defined. In the absence of randomized studies, the review aims to identify any recent literature that helps define the role. RECENT FINDINGS: In differentiated thyroid cancer, single institutional studies report durable locoregional disease control in patients considered to be at high risk of local relapse after EBRT and recent guidelines are consistent in their recommendations. In medullary thyroid cancer, the evidence is more limited but again there is benefit in selected cases. In anaplastic thyroid cancer, multimodality therapy is superior to surgery alone in achieving local control and possibly survival but the benefit must be weighed against the toxicity. Newer radiation techniques may help reduce toxicity. SUMMARY: Although surgery is the main treatment for thyroid carcinoma, EBRT has a role in the adjuvant setting following surgery in high-risk patients and in unresectable cancer. Advances in the delivery of external beam radiotherapy, including intensity-modulated radiotherapy reduces toxicity. PMID- 24225416 TI - Molecular diagnostic testing and the indeterminate thyroid nodule. AB - PURPOSE OF REVIEW: To summarize the latest developments in the use of molecular diagnostic testing in cytologically indeterminate thyroid nodules. RECENT FINDINGS: The majority of nodules with fine needle aspiration biopsy (FNAB) results that are classified as indeterminate (i.e., atypia of undetermined significance/lesion of undetermined significance, follicular neoplasm, and suspicious for malignancy) are histologically benign. Improvements in diagnostic discrimination can potentially be achieved with immunocytochemical analysis for candidate protein markers such as galectin-3, or analysis of differential microRNA expression patterns although larger prospective validation studies are still needed. After large-scale gene expression analysis, a marker panel was selected with the goal of optimizing the negative predictive value, and in indeterminate nodules, the panel may be helpful in lowering but not eliminating the risk of cancer. Another panel composed of gene mutations and rearrangements associated with thyroid cancer can improve the specificity and positive predictive value of preoperative FNAB, and better identify cytologically indeterminate nodules with a high risk of cancer. SUMMARY: Molecular diagnostic testing improves preoperative risk stratification for nodules that have indeterminate FNAB results. Although currently available tests do not yet have the sensitivity to reliably exclude malignancy altogether, improvements in specificity can be used to guide the extent of initial surgery and clinical management. PMID- 24225417 TI - The genetic-metabolic duality of cancer. PMID- 24225418 TI - Mission of randomness. PMID- 24225419 TI - Modulation in the expression of SHP-1, SHP-2 and PTP1B due to the inhibition of MAPKs, cAMP and neutrophils early on in the development of cerulein-induced acute pancreatitis in rats. AB - The protein tyrosine phosphatases (PTPs) SHP-1, SHP-2 and PTP1B are overexpressed early on during the development of cerulein -induced acute pancreatitis (AP) in rats, and their levels can be modulated by some species of mitogen-activated protein kinases (MAPKs), the intracellular levels of cAMP and by general leukocyte infiltration, the latter at least for SHP-2 and PTP1B. In this study we show that cerulein treatment activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) but not p38 MAPK during the early phase of cerulein-induced AP (2h after the first injection of cerulein). Therefore, by using the MAPK inhibitors SP600125 (a specific JNK inhibitor) and PD98059 (a specific ERK inhibitor), we have unmasked the particular MAPK that underlies the modulation of the expression levels of these PTPs. JNK would act by preventing SHP-1 protein expression from increasing beyond a certain level. ERK 1/2 was the main MAPK involved in the increase in SHP-2 protein expression due to cerulein. JNK negatively modulated the SH2-domain containing PTPs. Both MAPKs played a role in the increase in PTP1B protein expression due to cerulein. Finally, by using the white blood cell inhibitors vinblastine sulfate, gadolinium chloride and FK506 (tacrolimus), we show that the macrophage activity or T-lymphocytes does not modulate the expression of any of the PTPs, although neutrophil infiltration was found to be a regulator of SHP-2 and PTP1B protein expression due to cerulein. PMID- 24225420 TI - ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease. AB - The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domains. As such, delineating the functional pathways for LRRK2 and mechanisms by which PD-linked variants contribute to age-related neurodegeneration could result in pharmaceutically tractable therapies. A growing number of recent studies implicate dysregulation of mitogen activated protein kinases 3 and 1 (also known as ERK1/2) as possible downstream mediators of mutant LRRK2 effects. As these master regulators of growth, differentiation, neuronal plasticity and cell survival have also been implicated in other PD models, a set of common cell biological pathways may contribute to neuronal susceptibility in PD. Here, we review the literature on several major cellular pathways impacted by LRRK2 mutations--autophagy, microtubule/cytoskeletal dynamics, and protein synthesis- in context of potential signaling crosstalk involving the ERK1/2 and Wnt signaling pathways. Emerging implications for calcium homeostasis, mitochondrial biology and synaptic dysregulation are discussed in relation to LRRK2 interactions with other PD gene products. It has been shown that substantia nigra neurons in human PD and Lewy body dementia patients exhibit cytoplasmic accumulations of ERK1/2 in mitochondria, autophagosomes and bundles of intracellular fibrils. Both experimental and human tissue data implicate pathogenic changes in ERK1/2 signaling in sporadic, toxin-based and mutant LRRK2 settings, suggesting engagement of common cell biological pathways by divergent PD etiologies. PMID- 24225422 TI - Urban PM source apportionment mapping using microscopic chemical imaging. AB - To evaluate the health impacts of particulate matter and develop effective pollutant abatement strategies, one needs to know the source contributions to the observed concentrations. The most common approach involves the collection of ambient air samples on filters, laboratory analyses to quantify the chemical composition, and application of receptor modeling methods. This approach is expensive and time consuming and limits the ability to monitor the temporal and spatial impacts from different pollutant sources. An alternative method for apportioning the sources of ambient PM is the application of microscopic chemical imaging (MCI). The MCI method involves measuring individual particle's fluorescence and source attribution is based on the individual particle analysis coupled with identification from a source library. Using this approach, the apportionment of ambient PM can be performed in near real time, which allows for the generation of temporal and spatial maps of pollutant source impacts in an urban area. PMID- 24225423 TI - Vertebral compression exacerbates osteoporotic pain in an ovariectomy-induced osteoporosis rat model. AB - STUDY DESIGN: Basic pain study using osteoporotic rodent models. OBJECTIVE: To examine alterations in distribution of pain-related neuropeptides after compressive force on osteoporotic vertebrae and their chronic pain-related properties. SUMMARY OF BACKGROUND DATA: We previously reported significantly increased production of calcitonin gene-related peptide (CGRP), a marker of inflammatory pain, in the dorsal root ganglia (DRG) of vertebrae in osteoporosis model ovariectomized (OVX) rats. Here, we hypothesized that longitudinal compressive force on vertebrae can affect osteoporotic pain properties, which has not been examined yet. METHODS: OVX rats were used as the osteoporosis model. Female Sprague-Dawley rats were prepared and Fluoro-Gold (FG) neurotracer was applied to the periosteal surface of the Co5 vertebra. After FG labeling, the animals were divided into 4 groups: Control, Control + compression, OVX, and OVX + compression. The Control groups were not ovariectomized. In the compression groups, K-wires were stabbed transversely through Co4 and Co6 with Co5 compressed longitudinally by rubber bands bridged between the 2. One, 2, 4, and 8 weeks after surgery, bilateral S1 to S3 DRGs were excised for immunofluorescence assays. Expression of CGRP and activating transcription factor 3, a marker of neuronal injury, were compared among the 4 groups. RESULTS: Sustained upregulation of CGRP in DRG neurons was observed after compression of the Co5 vertebra, and Co5 compression caused significant increase in CGRP production in DRG neurons, whereas a greater level of activating transcription factor 3 upregulation was observed in DRGs in OVX rats after dynamic vertebral compression 8 weeks after surgery, implying potential neuropathic pain. CONCLUSION: There was sustained upregulation of CGRP and activating transcription factor 3 in DRGs in osteoporotic model rats compared with controls, and levels were further enhanced by dynamic vertebral compression. These findings imply that dynamic compression stress on vertebrae can exacerbate osteoporotic pain by inducing both inflammatory and neuropathic pain mediators. LEVEL OF EVIDENCE: N/A. PMID- 24225421 TI - Biofilms: an advancement in our understanding of Francisella species. AB - Our understanding of the virulence and pathogenesis of Francisella spp. has significantly advanced in recent years, including a new understanding that this organism can form biofilms. What is known so far about Francisella spp. biofilms is summarized here and future research questions are suggested. The molecular basis of biofilm production has begun to be studied, especially the role of extracellular carbohydrates and capsule, quorum sensing and two-component signaling systems. Further work has explored the contribution of amoebae, pili, outer-membrane vesicles, chitinases, and small molecules such as c-di-GMP to Francisella spp. biofilm formation. A role for Francisella spp. biofilm in feeding mosquito larvae has been suggested. As no strong role in virulence has been found yet, Francisella spp. biofilm formation is most likely a key mechanism for environmental survival and persistence. The significance and importance of Francisella spp.'s biofilm phenotype as a critical aspect of its microbial physiology is being developed. Areas for further studies include the potential role of Francisella spp. biofilms in the infection of mammalian hosts and virulence regulation. PMID- 24225424 TI - Preferential scattering by interfacial charged defects for enhanced thermoelectric performance in few-layered n-type Bi2Te3. AB - Over the past two decades several nano-structuring methods have helped improve the figure of merit (ZT) in the state-of-the art bulk thermoelectric materials. While these methods could enhance the thermoelectric performance of p-type Bi2Te3, it was frustrating to researchers that they proved ineffective for n-type Bi2Te3 due to the inevitable deterioration of its thermoelectric properties in the basal plane. Here, we describe a novel chemical-exfoliation spark-plasma sintering (CE-SPS) nano-structuring process, which transforms the microstructure of n-type Bi2Te3 in an extraordinary manner without compromising its basal plane properties. The CE-SPS processing leads to preferential scattering of electrons at charged grain boundaries, and thereby increases the electrical conductivity despite the presence of numerous grain boundaries, and mitigates the bipolar effect via band occupancy optimization leading to an upshift (by ~ 100 K) and stabilization of the ZT peak over a broad temperature range of ~ 150 K. PMID- 24225429 TI - DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1alpha in type 2 diabetic patients with incipient nephropathy. AB - Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new class of anti-diabetic drug which exerts its glucose-lowering action by suppressing the degradation of a gut incretin hormone glucagon-like peptide-1 (GLP-1). To elucidate whether treatment with stronger DPP-4 inhibitor on top of angiotensin II type 1 receptor blocker (ARB) provides greater renal protective effects, we performed a crossover study with two DPP-4 inhibitors, sitagliptin and alogliptin, in twelve type 2 diabetic patients with incipient nephropathy taking ARBs. This study consisted of three treatment periods: sitagliptin 50 mg/day for 4 weeks (first period), alogliptin 25 mg/day for 4 weeks (second period), and sitagliptin 50 mg/day for 4 weeks (third period). Significant changes in body mass index, blood pressure, serum lipids, serum creatinine, estimated glomerular filtration rate, and HbA1c were not observed among the three treatment periods. Reduced urinary levels of albumin and an oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased urinary cAMP levels, and elevated plasma levels of stromal cell-derived factor 1alpha (SDF-1alpha) which is a physiological substrate of DPP-4 were observed after the switch from sitagliptin to a stronger DPP-4 inhibitor alogliptin. Given a large body of evidence indicating anti-oxidative action of cAMP and up regulation of cellular cAMP production by SDF-1alpha, the present results suggest that more powerful DPP-4 inhibition on top of angiotensin II type 1 receptor blockade would offer additional protection against early-stage diabetic nephropathy beyond that attributed to glycemic control, via reduction of renal oxidative stress by SDF-1alpha-cAMP pathway activation. PMID- 24225430 TI - Synthesis and photophysics of reverse saturable absorbing heteroleptic iridium(III) complexes bearing 2-(7-R-fluoren-2'-yl)pyridine ligands. AB - Three new heteroleptic cationic iridium(III) complexes (1-3) bearing 5,5'-bis(7 benzothiazolylfluoren-2'-yl)-2,2'-bipyridine (N^N) and 2-(7-R-fluoren-2' yl)pyridine (R = H, naphthalimide, NPh2) (C^N) ligands were synthesized and characterized. Their photophysical properties were investigated systematically by UV-vis absorption, emission, and transient absorption spectroscopy, and the UV vis absorption spectra were simulated by time-dependent density functional theory (TDDFT). All complexes exhibit ligand-centered (1)pi,pi* transitions with minor contributions from (1)ILCT (intraligand charge transfer, pi(benzothiazolylfluorene) -> pi* (bpy)) and (1)MLCT (metal-to-ligand charge transfer, dpi(Ir) -> pi* (bpy)) transitions below 475 nm, and very weak (1,3)MLCT and (1,3)LLCT (ligand-to-ligand charge transfer, pi(C^N) -> pi* (bpy)) transitions above 475 nm. Complexes 1-3 are weakly emissive in fluid solution at room temperature and in glassy matrix at 77 K. The emission of 2 in toluene solution is possibly dominated by the substituted bipyridine ligand-localized (3)pi,pi* emission, while 1 and 3 likely exhibit (3)MLCT/(3)LLCT dominated emission in toluene solution. All complexes possess relatively strong triplet transient absorption (TA) from visible to NIR region, where reverse saturable absorption (RSA) could occur. Nonlinear transmission experiments at 532 nm using ns laser pulses demonstrate that all three complexes exhibit strong RSA, with the RSA strength following this trend: 1 >3 > 2. The different substituents on the fluorenyl groups of the C^N ligands alter the energy and lifetime of the lowest singlet and triplet excited states. They also affect the ground-state and excited state absorption characteristics. The differences in the ratio of the excited state absorption to that of the ground state and the triplet excited-state quantum yield result in the different degrees of RSA. Complexes 1-3 are strong reverse saturable absorbers at 532 nm and could potentially be used as broadband nonlinear absorbing materials. PMID- 24225431 TI - Activity-based diubiquitin probes for elucidating the linkage specificity of deubiquitinating enzymes. AB - We report a new class of deubiquitinating enzyme (DUB) probes that resemble the native diubiquitin with a same linkage size and contain a Michael addition acceptor for trapping the DUB active-site cysteine. Both K63- and K48-linked diubiquitin probes were generated using a facile chemical ligation method. The diUb probes were demonstrated to label DUBs from different families and revealed intrinsic linkage specificities of DUBs. PMID- 24225432 TI - Water VBAC: exploring a new frontier for women's autonomy. AB - BACKGROUND: although Vaginal Birth After Caesarean section (VBAC) has been promoted successfully as one means of reducing the caesarean section rate, the practice of VBAC using water immersion (Water VBAC) is restricted. Very little valid, reliable research evidence is available on this birth method, although initial small-scale audits indicate that Water VBAC has no adverse effect on maternal and neonatal outcomes. METHOD: in-depth semi-structured interviews were carried out with a purposive sample of eight women who had undergone Water VBAC in one midwife-led unit. The interviews aimed to explore their reasons for requesting this birthing method, and their experience of the process. An interpretative phenomenological analytical approach was adopted. FINDINGS: the women pursued Water VBAC for two main reasons: in order to prevent a repeat of the obstetric events that previously led to a caesarean section, and to counteract their previous negative birth experiences. The women reported improved physical and psychological outcomes from their Water VBAC experience when compared with their previous experience of caesarean section. Three main themes emerged: 'minimising', 'maximising' and 'managing'. Water VBAC entailed an attempt to minimise the medicalisation of the women's childbirth experience. This was achieved by limiting medical staff input in favour of midwife-led care, which was believed to minimise negative physical and psychological experiences. Correspondingly, Water VBAC was perceived as maximising physical and psychological benefits, and as a means of allowing women to obtain choice and assert control over their labour and birth. The women planning a Water VBAC believed they had to manage the potential risks associated with Water VBAC, as well as manage the expectations and behaviour of friends, family and the health care professionals involved in their care. CONCLUSIONS: for the women participating in this research, actively pursuing Water VBAC constituted a means of asserting their autonomy over the childbirth process. The value accorded to being able to exercise choice and control over their childbearing experience was high. These women's accounts indicated that information-giving and shared decision-making require improvement, and that inconsistencies in the attitudes of health care professionals need to be addressed. PMID- 24225434 TI - The utility of Criterion A under chronic national terror. AB - According to DSM-IV-TR, both an objective and a subjective exposure component (A1 and A2 criteria, respectively) are required in order to qualify for a Posttraumatic stress Disorder (PTSD) diagnosis. one proposed DSM-5 change is that Criterion A be more explicitly defined and made purely objective. the DSM and the ICD appear to be largely products of the north american and european societies and, therefore, may be culturally-biased. Compared with other societies, the latter are not exposed to chronic national traumatic stress. therefore, the current structure of Criterion A may be especially relevant to single traumatic incidents, rather than to chronic national scale. the current review raises the question of whether the proposed DSM-5 changes to Criterion A are congruent with the reality of nations where exposure to terror is persistent, constant and of national proportions. PMID- 24225433 TI - Human immunodeficiency virus type 1 viral protein R (Vpr) induces CCL5 expression in astrocytes via PI3K and MAPK signaling pathways. AB - BACKGROUND: Neurocognitive impairments remain prevalent in HIV-1 infected individuals despite current antiretroviral therapies. It is increasingly becoming evident that astrocytes play a critical role in HIV-1 neuropathogenesis through the production of proinflammatory cytokines/chemokines. HIV-1 viral protein R (Vpr) plays an important role in neuronal dysfunction; however, its role in neuroinflammation is not well characterized. The major objective of this study was to determine the effect of Vpr in induction of proinflammatory chemokine CCL5 in astrocytes and to define the underlying mechanism(s). METHODS: SVGA astrocytes were either mock transfected or were transfected with a plasmid encoding HIV-1 Vpr, and the cells were harvested at different time intervals. The mRNA level of CCL5 expression was quantified using real-time RT-PCR, and cell culture supernatants were assayed for CCL5 protein concentration. Immunocytochemistry was performed on HIV-1 Vpr transfected astrocytes to check CCL5 expression. Various signaling mechanisms such as p38 MAPK, PI3K/Akt, NF-kappaB and AP-1 were explored using specific chemical inhibitors and siRNAs. RESULTS: HIV-1 Vpr transfected astrocytes exhibited time-dependent induction of CCL5 as compared to mock transfected astrocytes at both the mRNA and protein level. Immunostained images of astrocytes transfected with HIV-1 Vpr also showed much higher accumulation of CCL5 in comparison to untransfected and mock-transfected astrocytes. Pre treatment with NF-kappaB (SC514) and PI3K/Akt (LY294002) inhibitor partially abrogated CCL5 mRNA and protein expression levels as opposed to untreated controls after HIV-1 Vpr transfection. Specific siRNAs against p50 and p65 subunits of NF-kappaB, p38delta MAPK, Akt-2 and Akt-3, and AP-1 transcription factor substantially inhibited the production of CCL5 in HIV-1 Vpr transfected astrocytes. CONCLUSION: These results demonstrate the ability of HIV-1 Vpr to induce CCL5 in astrocytes in a time-dependent manner. Furthermore, this effect was observed to be mediated by transcription factors NF-kappaB and AP-1 and involved the p38-MAPK and PI3K/Akt pathway. PMID- 24225435 TI - Elaboration on posttraumatic stress disorder diagnostic criteria: a factor analytic study of PTSD exposure to war or terror. AB - BACKGROUND: In societies facing prolonged exposure to war and terror, empirical research provides mixed support for the posttraumatic stress disorder (PTSD) symptom clusters groupings identified by the Diagnostic and Statistical Manual (DSM-IV-TR) as re-experiencing the event, avoidance and emotional numbing, and hyperarousal. METHOD: This study examines the validity of the PTSD symptom clusters in elements of Israeli society exposed to man-made trauma. Survivors (N=2,198) of seven different war and terror-related traumas were assessed using a DSM-IV-TR based PTSD inventory. Four confirmatory factor analytic models were compared. RESULTS/CONCLUSIONS: The most acceptable model was a correlated model consisting of four factors of re-experiencing, avoidance, emotional numbing, and hyperarousal. DSM-IV-TR avoidance empirically split into active avoidance and emotional numbing. These results corroborate knowledge and suggest that in Israel, where stressors are ongoing, the PTSD symptom clusters may be reformulated in DSM-5 to consist of re-experiencing, active avoidance, emotional numbing and hyperarousal. PMID- 24225436 TI - PTSD, resilience and posttraumatic growth among ex-prisoners of war and combat veterans. AB - BACKGROUND: Past studies have shown that adversity may yield various salutogenic outcomes. two constructs that have been at the center of this scientific investigation are resilience and posttraumatic growth (PTG). the present study aims to clarify the relations between posttraumatic stress symptoms, resilience and PTG among israeli war veterans. METHOD: the sample includes former prisoners of war (ex-POWs) (n=103) and comparable veterans (n=106) of the 1973 Yom Kippur War. the veterans were assessed twice: 18 and 30 years after the war with self report questionnaires. RESULTS: resilience, defined as the absence of posttraumatic symptoms, and PTG are negatively correlated. resilient ex- POWs and veterans reported the lowest levels of PTG when compared to participants diagnosed with clinical and sub-clinical posttraumatic stress disorder (PtSd). Furthermore, PTG dimensions were found to be the most differentiating factor between study groups, followed by war exposure measures and clinical reports of depression and anxiety symptoms. CONCLUSIONS: this study strengthens the understanding that combatants who report high-level PtSd symptoms also report higher levels of positive psychological changes in the face of severe adversity. PMID- 24225437 TI - A longitudinal study of changes in psychological responses to continuous terrorism. AB - OBJECTIVE: The impact of ongoing terror over time has received little attention. This study assesses longitudinally prevalence and predictors of posttraumatic stress symptoms' trajectories, namely resistance, resilience, late-onset and chronicity in the course of intensive and ongoing terror. METHOD: Two surveys were performed at a two-year interval among 153 Jewish Israeli adults. RESULTS: Results show probable PTSD prevalence, number of traumatic stress related symptoms (TSRS), and rate of severe posttraumatic symptomatology (PTSS) to increase over time (from 18.2% to 31.2%). With this, many (66.7% of those with PTSD and 39.3% of those with PTSS at wave 1) recovered. Late-onset of severe PTSS (19.6% of the sample) was predicted by income reduction, a major lifetime traumatic event, sense of threat, dissociation, coping via disengagement and low mood. Chronicity was predicted by sense of threat, pessimism, dissociation and disengagement. CONCLUSIONS: Continuous exposure to terror has a strong negative impact on mental health. Secondly, even within a chronic situation of terror, a large proportion of individuals with elevated levels of posttraumatic symptomatology recover over time; third, prolonged exposure to terror may also exacerbate symptomatology, but not per-se trigger new PTSD cases. PMID- 24225438 TI - Sense of coherence and sense of community as coping resources of religious adolescents before and after the disengagement from the Gaza Strip. AB - In August 2005, all of the Jewish communities in the Gaza Strip were permanently evacuated, implementing a political decision of the Israeli government. Employing the salutogenic approach, this study explores individual and community coping resources - sense of coherence and sense of community - among adolescents who were displaced from their homes. We examined the way these coping resources operated in three stages: before the disengagement from Gaza, a few months after the event, and five years after the disengagement. Data were gathered among religious adolescents who had grown up in small Jewish communities in the Gaza Strip. Adolescents aged 12-18 filled out self-reported questionnaires, evaluating state anxiety and state anger as stress reactions, and sense of coherence and sense of community as coping resources. Results suggest that both sense of coherence and sense of community were weakened immediately after the disengagement. However, sense of coherence has recovered five years after the event. Furthermore, during the two stages after the disengagement, sense of coherence and sense of community had more explanatory power of stress reactions than during the acute state. Results are discussed against the backdrop of the salutogenic model, including practical implications for different interventions which should be applied in various states of stress. PMID- 24225439 TI - Trauma and psychological distress observed in journalists: a comparison of Israeli journalists and their Western counterparts. AB - BACKGROUND: There is limited evidence on how reporting war influences journalists' psychological wellbeing. A significant minority of journalists may develop symptoms of emotional distress; however it is unclear whether the type and amount of distress differs between those journalists who report from potentially dangerous areas within their own country compared to those who do so from war zones in other countries. METHOD: We compared indices of psychological health in 38 Israeli journalists with 38 Western journalists whose careers have been defined by work in war zones. RESULTS: While both groups reported high levels of exposure to traumatic events, there were no significant differences in frequency or type of exposure between the groups. Western journalists reported more frequent posttraumatic stress disorder (PTSD), intrusion-type symptoms and drank more alcohol while Israeli journalists reported higher levels of depression, anxiety and somatic distress. CONCLUSION: This pattern of results suggests that social circumstances and environmental factors may influence how different groups of individuals respond to traumatic events. PMID- 24225440 TI - Ethical considerations during times of conflict: challenges and pitfalls for the psychiatrist. AB - Despite the advances of civilization, conflict remains in many areas around the world. Often psychiatry finds itself playing an essential role in dealing with the consequences of conflict or influencing the process. Along with this involvement comes great responsibility as well as many associated ethical dilemmas. Although bound by professional medical oaths, many physicians disregard fundamental medical ethical principles during times of conflict and situations of "dual loyalty." The phenomenon should be addressed so that ethical awareness and sensitivity to these issues are nurtured. Important factors for psychiatrists during times of conflict to consider include their "social contract" with the community, dangers of boundary violations, the ethics of media contact, involvement in governmental and political activities and confidentiality. In addition, their role in conflict resolution and unique ethical considerations in the military should be considered. While as regular citizens, psychiatrists in their individual capacity may involve themselves in political activism, at an organizational level it should be discouraged. A physician's skills should only be exploited to save lives and provide comfort as entrusted by society, and any other pursuit, even in the name of the state, should be proscribed. Rather than engage in political activism, psychiatrists can promote the rights of patients, especially if these rights are limited during conflict. Responsibility and ethically-driven commitment needs to be primary for the psychiatrist who involves himself either directly or indirectly with patients during times of conflict. Trauma and its effects during conflict should be addressed without any unbalanced attention to pathological responses. PMID- 24225441 TI - On the links between religion, mental health and inter-religious conflict: a brief summary of empirical research. AB - Recently, the field of psychology has begun to display a growing interest in the influence of religion on people's psychological well-being. By and large, the empirical findings of this body of inquiry have revealed positive associations between religious beliefs and practices and different indices of health and well being and demonstrated that religion serves as a valuable tool for individuals dealing with life stressors. Yet, there is ample data to suggest that religion can also have a negative influence on the psychological well-being of the individual. This duality of religion is the focus of this summary paper which consists of two main sections. The first considers the potential constructive and destructive sides of religion with regard to general health and well- being. The second section refers to religious variables that promote or mitigate prejudice and perceived conflict with others. PMID- 24225443 TI - Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse. AB - The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture. PMID- 24225444 TI - Measuring the quality of vision after cataract surgery. AB - PURPOSE OF REVIEW: The purpose of this review is to report some of the latest advances in visual acuity measurements and to review key articles on quality of visual after cataract surgery with intraocular lens (IOL) implantation. RECENT FINDINGS: Different quality of life instruments were used in the most recent studies and showed improvements in subjective quality of vision after cataract surgery with or without ocular comorbidities and independent of the type of IOL implanted. The use of multifocal IOLs improved near vision without any adverse effect on distance acuity. Contrast sensitivity was lower in patients with multifocal IOLs. Femtosecond laser cataract surgery increased predictability of the steps involved in cataract surgery but has a definite learning curve associated with an initial high rate of complications. Toric IOLs showed significant improvement in uncorrected distant visual acuity with low amount of decentration and wavefront error. Incorporating the testing of visual acuity in real-life scenarios that patients encounter routinely using automated instruments promises to transform visual assessment in a rapid manner that can be integrated into clinical practice. SUMMARY: Visual outcomes of cataract surgery with IOL implantation generally yield highly satisfactory results. Newer cataract surgery technology has emerged in an era wherein patients are demanding excellent visual results. Changes in the way we normally assess routine visual acuities should be implemented. We have introduced testing of visual acuity in timed, real-life scenarios that patients encounter daily, in an automated instrument, which may help us better document patient's complaints and surgical outcomes. PMID- 24225442 TI - Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization. AB - During apoptosis, phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and serves as an 'eat-me' signal to trigger phagocytosis. It is poorly understood how PS exposure is activated in apoptotic cells. Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. Cleavage of CED-8 by CED-3 activates its proapoptotic function and generates a carboxyl-terminal cleavage product, acCED-8, that promotes PS externalization in apoptotic cells and can induce ectopic PS exposure in living cells. Consistent with its role in promoting PS externalization in apoptotic cells, ced-8 is important for cell corpse engulfment in C. elegans. Our finding identifies a crucial link between caspase activation and PS externalization, which triggers phagocytosis of apoptotic cells. PMID- 24225445 TI - Cadherin AdCad1 in Alphitobius diaperinus larvae is a receptor of Cry3Bb toxin from Bacillus thuringiensis. AB - Bacillus thuringiensis (Bt) Cry proteins are used as components of biopesticides or expressed in transgenic crops to control diverse insect pests worldwide. These Cry toxins bind to receptors on the midgut brush border membrane and kill enterocytes culminating in larval mortality. Cadherin proteins have been identified as Cry toxin receptors in diverse lepidopteran, coleopteran, and dipteran species. In the present work we report a 185 kDa cadherin (AdCad1) from larvae of the lesser mealworm (Alphitobius diaperinus) larvae as the first identified receptor for Cry3Bb toxin. The AdCad1 protein contains typical structural components for Cry toxin receptor cadherins, including nine cadherin repeats (CR9), a membrane-proximal extracellular domain (MPED) and a cytosolic region. Peptides corresponding to the CR9 and MPED regions bound Cry3Bb toxin with high affinities (23 nM and 40 nM) and significantly synergized Cry3Bb toxicity against A. diperinus larvae. Silencing of AdCad1 expression through RNA interference resulted in highly reduced susceptibility to Cry3Bb in A. diperinus larvae. The CR9 peptide fed with toxin to RNAi-treated larvae restored Cry3Bb toxicity. These results are evidences that AdCad1 is a functional receptor of Cry3Bb toxin and that exogenously fed CR9 peptide can overcome the effect of reduced AdCad1expression on Cry3Bb toxicity to larvae. PMID- 24225446 TI - Painfully obvious: a longitudinal examination of medical use and misuse of opioid medication among adolescent sports participants. AB - PURPOSE: The objective of this longitudinal study was to assess the prevalence of medical use, medical misuse, and non-medical use of opioid medication among adolescents who participate in organized sports. METHODS: Data for this study were taken from the Secondary Student Life Survey. A total of 1,540 adolescents participated in three waves of data collection occurring between the 2009-2010 and 2011-2012 school years, with 82% of the baseline sample completing all three waves. RESULTS: Using generalized estimating equation models to analyze the longitudinal data, it was found that male adolescents who participated in organized sports during each wave of the Secondary Student Life Survey had higher odds of being prescribed an opioid medication (i.e., medical use) during the past year (adjusted odds ratio [AOR], 1.86; 95% confidence interval [CI], 1.23-2.82), higher odds of past-year medical misuse of opioid medication as a result of taking too much (AOR, 10.5; 95% CI, 2.42-45.5), and higher odds of past-year medical misuse of opioid medication to get high (AOR, 4.01; 95% CI, 1.13-14.2) compared with males who did not participate in organized sports during the study period. Among females, no association was found between participation in organized sports and medical use, medical misuse, and non-medical use of opioid medication. CONCLUSIONS: The results of this study indicate that adolescent males who participate in sports may have greater access to opioid medication, which puts them at greater risk to misuse these controlled substances. PMID- 24225448 TI - Oxytocin decreases accuracy in the perception of social deception. PMID- 24225447 TI - The effects of bedtime and sleep duration on academic and emotional outcomes in a nationally representative sample of adolescents. AB - PURPOSE: The overall aim of this study was to clarify and better characterize the sleep/circadian patterns of adolescents in a nationally representative sample. METHODS: We used three waves of data from the National Longitudinal Study of Adolescent Health to assess sleep/circadian patterns of 2,700 adolescents in grades seven through 12. RESULTS: Late school year bedtime was associated with shorter total sleep time cross-sectionally, whereas late summertime bedtime was not. Moreover, late school year bedtime was not associated with late summertime bedtime cross-sectionally. Late school year bedtime in Wave I (1994-1995) was associated with worse educational outcomes and emotional distress 6-8 years later. In addition, late summertime bedtime in Wave II (1996) was associated with more emotional distress at Wave III (2001-2002). Short total sleep time was not associated longitudinally with changes in emotional and academic functioning. Across Waves I and II, more than three quarters of adolescents who went to sleep at 11:15 a.m. or later during the school year or 1:30 a.m. or later during the summer reported sleeping fewer than the recommended 9 hours. CONCLUSIONS: These findings underscore the significance of evaluating and monitoring bedtime in adolescents and the importance of intervention strategies that target bedtimes in an effort to reduce associated functional impairments, and improve academic and emotional outcomes. PMID- 24225449 TI - Plasma and erythrocyte fatty acids reflect intakes of saturated and n-6 PUFA within a similar time frame. AB - Erythrocytes, compared with plasma, are considered more robust markers of n-3 (omega-3) polyunsaturated fatty acid (PUFA) intake, because dietary-induced change in fatty acid (FA) composition takes longer to complete. The extent to which this applies to intakes of saturated fatty acid (SFA) or n-6 PUFA is unclear. We compared the pattern of change over time in the fatty acid composition of plasma, erythrocyte, buccal cell, and adipose tissue lipids when changing between diets high in SFA or n-6 PUFA. Twenty-four (n = 7 male) healthy participants were instructed to consume either an SFA-rich (18% energy) or n-6 PUFA-rich (10% energy) diet for 8 wk before crossing over, without washout, to the alternate diet. The FA composition of plasma triacylglycerol (TG), nonesterified FAs, cholesterol ester, total phospholipids, erythrocyte total phospholipids, erythrocyte phosphatidylcholine, and buccal cell total phospholipids was measured every 2 wk and adipose tissue TG every 4 wk during the 16-wk intervention. Linoleic acid composition of plasma, erythrocyte, and buccal cell lipids increased (P < 0.01) during the first 2 wk of the n-6 PUFA diet and remained unchanged during the remaining 6 wk. During the 8-wk SFA diet, the same pattern of change over time occurred for the pentadecanoic acid composition of plasma and erythrocyte lipids; however, the pentadecanoic acid composition of buccal cell lipids did not differ between the diet periods. There were no differences in linoleic or pentadecanoic acid composition of adipose tissue TG. These results suggest plasma and erythrocyte FAs reflect intakes of SFA and n-6 PUFA over a similar period of time. PMID- 24225450 TI - Daidzein supplementation decreases serum triglyceride and uric acid concentrations in hypercholesterolemic adults with the effect on triglycerides being greater in those with the GA compared with the GG genotype of ESR-beta RsaI. AB - Daidzein (one of the major isoflavones) can be metabolized to equol in certain individuals. The effects of isoflavones alone and equol status on lipid profiles are still controversial. To evaluate the 6-mo effects of daidzein on cardiovascular risk factors in hypercholesterolemic individuals and the interactions of these effects with equol status and estrogen receptor (ESR) genotypes, we conducted a randomized, double-blind, placebo-controlled trial consisting of 210 hypercholesterolemic adults (40-65 y old). The participants were randomly assigned (177 completed) to consume placebo, 40 mg daidzein (DAI40), or 80 mg daidzein (DAI80) daily for 6 mo. Daidzein decreased serum triglycerides (TGs) by 0.15 +/- 0.62 mmol/L (mean +/- SD) and 0.24 +/- 0.61 mmol/L and decreased serum uric acid by 23 +/- 47 MUmol/L and 29 +/- 44 MUmol/L in the DAI40 and DAI80 groups, respectively. These reductions in the DAI40 and DAI80 groups were greater than those in the placebo group (P < 0.05). Other blood lipids, glucose, insulin, or glycated hemoglobin did not significantly change after daidzein treatment. No dose-dependent effects of daidzein were found. The reduction of TGs was influenced by the ESR genotype, with a greater effect observed in participants with the GA genotype compared with those with the GG genotype of ESR-beta RsaI. These effects were not influenced by equol status. Six month supplementation of daidzein significantly decreased TGs and uric acid. ESR beta RsaI genotype, not equol status, influenced daidzein's effects on TGs. Daidzein consumption may be effective to improve cardiovascular risk factors, especially in adults with the GA genotype of ESR-beta RsaI. This trial was registered at the Chinese clinical trial registry as ChiCTR-TRC-10001048. PMID- 24225451 TI - Absorbed zinc and exchangeable zinc pool size are greater in Pakistani infants receiving traditional complementary foods with zinc-fortified micronutrient powder. AB - Adequacy of zinc intake from breast milk alone becomes marginal in relation to infant requirements by around 6 mo of age. Simple and cost-effective strategies are needed at the population level to ensure adequate intakes of zinc in infants and toddlers in populations at risk of zinc deficiency. We determined the amount of absorbed zinc (AZ) from a micronutrient powder (MNP) without and with 10 mg of zinc (MNP+Zn) added to local complementary foods used in Pakistan and the impact on the exchangeable zinc pool (EZP) size. As a nested study within a large, prospective, cluster randomized trial, 6-mo-old infants were randomly assigned to receive MNP or MNP+Zn. Stable isotope methodology was applied after ~3 and 9 mo of use to measure AZ from MNP-fortified test meals of rice-lentils (khitchri) and EZP. Nineteen infants per group completed the first metabolic studies and 14 and 17 infants in the MNP and MNP+Zn groups, respectively, completed the follow-up studies. AZs were (mean +/- SD) 0.1 +/- 0.1 and 1.2 +/- 0.5 mg at the first point for the MNP and MNP+Zn groups, respectively (P < 0.001); results were nearly identical at the follow-up measurement. EZP did not differ between groups at the first measurement but was less in the MNP group (3.7 +/- 0.6 mg/kg) than in the MNP+Zn group (4.5 +/- 1.0 mg/kg) at the second measurement (P = 0.01). These data confirm that the MNP+Zn in khitchri were well absorbed and after 1 y of home fortification, zinc status assessed by EZP was significantly better for the MNP+Zn group. Additional field studies may be necessary to ascertain the adequacy of this dose for infants at high risk of deficiency. This trial was registered at ClinicalTrials.gov as NCT00705445. PMID- 24225452 TI - Female rhesus macaques discriminate unfamiliar paternal sisters in playback experiments: support for acoustic phenotype matching. AB - Widespread evidence exists that when relatives live together, kinship plays a central role in shaping the evolution of social behaviour. Previous studies showed that female rhesus macaques (Macaca mulatta) recognize familiar maternal kin using vocal cues. Recognizing paternal kin might, however, be more difficult as rhesus females mate promiscuously during the possible conception period, most probably concealing paternity. Behavioural observations indicate that semi free ranging female rhesus macaques prefer to associate with their paternal half sisters in comparison to unrelated females within the same group, particularly when born within the same age cohort. However, the cues and mechanism/s used in paternal kin discrimination remain under debate. Here, we investigated whether female rhesus macaques use the acoustic modality to discriminate between paternal half-sisters and non-kin, and tested familiarity and phenotype matching as the underlying mechanisms. We found that test females responded more often to calls of paternal half-sisters compared with calls of unrelated females, and that this discrimination ability was independent of the level of familiarity between callers and test females, which provides, to our knowledge, the first evidence for acoustic phenotype matching. Our study strengthens the evidence that female rhesus macaques can recognize their paternal kin, and that vocalizations are used as a cue. PMID- 24225454 TI - Why is timing of bird migration advancing when individuals are not? AB - Recent advances in spring arrival dates have been reported in many migratory species but the mechanism driving these advances is unknown. As population declines are most widely reported in species that are not advancing migration, there is an urgent need to identify the mechanisms facilitating and constraining these advances. Individual plasticity in timing of migration in response to changing climatic conditions is commonly proposed to drive these advances but plasticity in individual migratory timings is rarely observed. For a shorebird population that has significantly advanced migration in recent decades, we show that individual arrival dates are highly consistent between years, but that the arrival dates of new recruits to the population are significantly earlier now than in previous years. Several mechanisms could drive advances in recruit arrival, none of which require individual plasticity or rapid evolution of migration timings. In particular, advances in nest-laying dates could result in advanced recruit arrival, if benefits of early hatching facilitate early subsequent spring migration. This mechanism could also explain why arrival dates of short-distance migrants, which generally return to breeding sites earlier and have greater scope for advance laying, are advancing more rapidly than long distance migrants. PMID- 24225455 TI - Alternative mating tactics in the yellow dung fly: resolving mechanisms of small male advantage off pasture. AB - Recent work suggests that the yellow dung fly mating system may include alternative patroller-competitor mating tactics in which large males compete for gravid females on dung, whereas small, non-competitive males search for females at foraging sites. Small males obtain most matings off pasture, yet the behavioural mechanism(s) giving rise to this pattern are unknown. We investigated the male and female behaviours that determine mating success in this environment by conducting field mating experiments and found small males to benefit from several attributes specific to the off-pasture mating environment. First, small males from foraging sites exhibited higher mating propensity, indicating that large males away from dung may be depleted of energy and/or sperm. Second, small males were more discriminating, being significantly less likely to attempt with non-gravid females, which are absent on dung but common off pasture. Third, non gravid females were generally more likely to actively struggle and reject mating attempts; however, such behaviours occurred disproportionately more often with large males. Female Scathophaga stercoraria thus appear to preferentially mate with small males when off pasture. These findings challenge assumptions about male-female interactions in systems with alternative mating tactics and reveal hidden processes that may influence selection patterns in the field. PMID- 24225453 TI - Correlations in the population structure of music, genes and language. AB - We present, to our knowledge, the first quantitative evidence that music and genes may have coevolved by demonstrating significant correlations between traditional group-level folk songs and mitochondrial DNA variation among nine indigenous populations of Taiwan. These correlations were of comparable magnitude to those between language and genes for the same populations, although music and language were not significantly correlated with one another. An examination of population structure for genetics showed stronger parallels to music than to language. Overall, the results suggest that music might have a sufficient time depth to retrace ancient population movements and, additionally, that it might be capturing different aspects of population history than language. Music may therefore have the potential to serve as a novel marker of human migrations to complement genes, language and other markers. PMID- 24225456 TI - Marine mollusc predator-escape behaviour altered by near-future carbon dioxide levels. AB - Ocean acidification poses a range of threats to marine invertebrates; however, the potential effects of rising carbon dioxide (CO2) on marine invertebrate behaviour are largely unknown. Marine gastropod conch snails have a modified foot and operculum allowing them to leap backwards rapidly when faced with a predator, such as a venomous cone shell. Here, we show that projected near-future seawater CO2 levels (961 uatm) impair this escape behaviour during a predator-prey interaction. Elevated-CO2 halved the number of snails that jumped from the predator, increased their latency to jump and altered their escape trajectory. Physical ability to jump was not affected by elevated-CO2 indicating instead that decision-making was impaired. Antipredator behaviour was fully restored by treatment with gabazine, a GABA antagonist of some invertebrate nervous systems, indicating potential interference of neurotransmitter receptor function by elevated-CO2, as previously observed in marine fishes. Altered behaviour of marine invertebrates at projected future CO2 levels could have potentially far reaching implications for marine ecosystems. PMID- 24225457 TI - Differential allocation in a lekking bird: females lay larger eggs and are more likely to have male chicks when they mate with less related males. AB - The differential allocation hypothesis predicts increased investment in offspring when females mate with high-quality males. Few studies have tested whether investment varies with mate relatedness, despite evidence that non-additive gene action influences mate and offspring genetic quality. We tested whether female lekking lance-tailed manakins (Chiroxiphia lanceolata) adjust offspring sex and egg volume in response to mate attractiveness (annual reproductive success, ARS), heterozygosity and relatedness. Across 968 offspring, the probability of being male decreased with increasing parental relatedness but not father ARS or heterozygosity. This correlation tended to diminish with increasing lay-date. Across 162 offspring, egg volume correlated negatively with parental relatedness and varied with lay-date, but was unrelated to father ARS or heterozygosity. Offspring sex and egg size were unrelated to maternal age. Comparisons of maternal half-siblings in broods with no mortality produced similar results, indicating differential allocation rather than covariation between female quality and relatedness or sex-specific inbreeding depression in survival. As males suffer greater inbreeding depression, overproducing females after mating with related males may reduce fitness costs of inbreeding in a system with no inbreeding avoidance, while biasing the sex of outbred offspring towards males may maximize fitness via increased mating success of outbred sons. PMID- 24225458 TI - Large-scale distribution of hybridogenetic lineages in a Spanish desert ant. AB - Recently, a unique case of hybridogenesis at a social level was reported in local populations of the desert ants Cataglyphis. Queens mate with males originating from a different genetic lineage than their own to produce hybrid workers, but they use parthenogenesis for the production of reproductive offspring (males and females). As a result, non-reproductive workers are all inter-lineage hybrids, whereas the sexual line is purely maternal. Here, we show that this unorthodox reproductive system occurs in all populations of the ant Cataglyphis hispanica. Remarkably, workers are hybrids of the same two genetic lineages along a 400 km transect crossing the whole distribution range of the species. These results indicate that social hybridogenesis in C. hispanica allows their maintenance over time and across a large geographical scale of two highly divergent genetic lineages, despite their constant hybridization. The widespread distribution of social hybridogenesis in C. hispanica supports that this reproductive strategy has been evolutionarily conserved over a long period. PMID- 24225459 TI - Cephalo-traumatic secretion transfer in a hermaphrodite sea slug. AB - Mating rituals in the animal kingdom are often quite extraordinary, in particular when mating is traumatic. We here describe the exceptional traumatic mating behaviour of the currently undescribed sea slug, Siphopteron sp. 1. Similar to four congeners, Siphopteron sp. 1 routinely exhibits traumatic secretion transfer through a stylet-like penis appendage. Contrary to previous descriptions, however, prostate secretions are injected centrally into the partner's forehead, representing, to our knowledge, the first-known instance of 'cephalo-traumatic secretion transfer'. We further provide a comparative quantification of within- and between-species variation in injection sites and derive a potential neurophysiological function of prostate secretions that are injected close to, or into, the central nervous system. PMID- 24225460 TI - Why not lie? Costs enforce honesty in an experimental signalling game. AB - Communication depends on reliability. Yet, the existence of stable honest signalling presents an evolutionary puzzle. Why should animals signal honestly in the face of a conflict of interest? While students of animal signalling have offered several theoretical answers to this puzzle, the most widely studied model, commonly called the 'handicap principle', postulates that the costs of signals stabilize honesty. This model is the motivating force behind an enormous research enterprise that explores signal costs--whether they are physiological, immunological, neural, developmental or caloric. While there can be no question that many signals are costly, we lack definitive experimental evidence demonstrating that costs stabilize honesty. This study presents a laboratory signalling game using blue jays (Cyanocitta cristata) that provides, to our knowledge, the first experimental evidence showing honesty persists when costs are high and disappears when costs are low. PMID- 24225461 TI - Sociality influences cultural complexity. AB - Archaeological and ethnohistorical evidence suggests a link between a population's size and structure, and the diversity or sophistication of its toolkits or technologies. Addressing these patterns, several evolutionary models predict that both the size and social interconnectedness of populations can contribute to the complexity of its cultural repertoire. Some models also predict that a sudden loss of sociality or of population will result in subsequent losses of useful skills/technologies. Here, we test these predictions with two experiments that permit learners to access either one or five models (teachers). Experiment 1 demonstrates that naive participants who could observe five models, integrate this information and generate increasingly effective skills (using an image editing tool) over 10 laboratory generations, whereas those with access to only one model show no improvement. Experiment 2, which began with a generation of trained experts, shows how learners with access to only one model lose skills (in knot-tying) more rapidly than those with access to five models. In the final generation of both experiments, all participants with access to five models demonstrate superior skills to those with access to only one model. These results support theoretical predictions linking sociality to cumulative cultural evolution. PMID- 24225462 TI - Social status and personality: stability in social state can promote consistency of behavioural responses. AB - Stability of 'state' has been suggested as an underlying factor explaining behavioural stability and animal personality (i.e. variation among, and consistency within individuals in behavioural responses), but the possibility that stable social relationships represent such states remains unexplored. Here, we investigated the influence of social status on the expression and consistency of behaviours by experimentally changing social status between repeated personality assays. We used male domestic fowl (Gallus gallus domesticus), a social species that forms relatively stable dominance hierarchies, and showed that behavioural responses were strongly affected by social status, but also by individual characteristics. The level of vigilance, activity and exploration changed with social status, whereas boldness appeared as a stable individual property, independent of status. Furthermore, variation in vocalization predicted future social status, indicating that individual behaviours can both be a predictor and a consequence of social status, depending on the aspect in focus. Our results illustrate that social states contribute to both variation and stability in behavioural responses, and should therefore be taken into account when investigating and interpreting variation in personality. PMID- 24225463 TI - Fitness benefits of low infectivity in a spatially structured population of bacteriophages. AB - For a parasite evolving in a spatially structured environment, an evolutionarily advantageous strategy may be to reduce its transmission rate or infectivity. We demonstrate this empirically using bacteriophage (phage) from an evolution experiment where spatial structure was maintained over 550 phage generations on agar plates. We found that a single substitution in the major capsid protein led to slower adsorption of phage to host cells with no change in lysis time or burst size. Plaques formed by phage isolates containing this mutation were not only larger but also contained more phage per unit area. Using a spatially explicit, individual-based model, we showed that when there is a trade-off between adsorption and diffusion (i.e. less 'sticky' phage diffuse further), slow adsorption can maximize plaque size, plaque density and overall productivity. These findings suggest that less infective pathogens may have an advantage in spatially structured populations, even when well-mixed models predict that they will not. PMID- 24225464 TI - How superdiffusion gets arrested: ecological encounters explain shift from Levy to Brownian movement. AB - Ecological theory uses Brownian motion as a default template for describing ecological movement, despite limited mechanistic underpinning. The generality of Brownian motion has recently been challenged by empirical studies that highlight alternative movement patterns of animals, especially when foraging in resource poor environments. Yet, empirical studies reveal animals moving in a Brownian fashion when resources are abundant. We demonstrate that Einstein's original theory of collision-induced Brownian motion in physics provides a parsimonious, mechanistic explanation for these observations. Here, Brownian motion results from frequent encounters between organisms in dense environments. In density controlled experiments, movement patterns of mussels shifted from Levy towards Brownian motion with increasing density. When the analysis was restricted to moves not truncated by encounters, this shift did not occur. Using a theoretical argument, we explain that any movement pattern approximates Brownian motion at high-resource densities, provided that movement is interrupted upon encounters. Hence, the observed shift to Brownian motion does not indicate a density dependent change in movement strategy but rather results from frequent collisions. Our results emphasize the need for a more mechanistic use of Brownian motion in ecology, highlighting that especially in rich environments, Brownian motion emerges from ecological interactions, rather than being a default movement pattern. PMID- 24225465 TI - Disentangling multiple drivers of pollination in a landscape-scale experiment. AB - Animal pollination is essential for the reproductive success of many wild and crop plants. Loss and isolation of (semi-)natural habitats in agricultural landscapes can cause declines of plants and pollinators and endanger pollination services. We investigated the independent effects of these drivers on pollination of young cherry trees in a landscape-scale experiment. We included (i) isolation of study trees from other cherry trees (up to 350 m), (ii) the amount of cherry trees in the landscape, (iii) the isolation from other woody habitats (up to 200 m) and (iv) the amount of woody habitats providing nesting and floral resources for pollinators. At the local scale, we considered effects of (v) cherry flower density and (vi) heterospecific flower density. Pollinators visited flowers more often in landscapes with high amount of woody habitat and at sites with lower isolation from the next cherry tree. Fruit set was reduced by isolation from the next cherry tree and by a high local density of heterospecific flowers but did not directly depend on pollinator visitation. These results reveal the importance of considering the plant's need for conspecific pollen and its pollen competition with co-flowering species rather than focusing only on pollinators' habitat requirements and flower visitation. It proved to be important to disentangle habitat isolation from habitat loss, local from landscape-scale effects, and direct effects of pollen availability on fruit set from indirect effects via pollinator visitation to understand the delivery of an agriculturally important ecosystem service. PMID- 24225466 TI - Himalayan fossils of the oldest known pantherine establish ancient origin of big cats. AB - Pantherine felids ('big cats') include the largest living cats, apex predators in their respective ecosystems. They are also the earliest diverging living cat lineage, and thus are important for understanding the evolution of all subsequent felid groups. Although the oldest pantherine fossils occur in Africa, molecular phylogenies point to Asia as their region of origin. This paradox cannot be reconciled using current knowledge, mainly because early big cat fossils are exceedingly rare and fragmentary. Here, we report the discovery of a fossil pantherine from the Tibetan Himalaya, with an age of Late Miocene-Early Pliocene, replacing African records as the oldest pantherine. A 'total evidence' phylogenetic analysis of pantherines indicates that the new cat is closely related to the snow leopard and exhibits intermediate characteristics on the evolutionary line to the largest cats. Historical biogeographic models provide robust support for the Asian origin of pantherines. The combined analyses indicate that 75% of the divergence events in the pantherine lineage extended back to the Miocene, up to 7 Myr earlier than previously estimated. The deeper evolutionary origin of big cats revealed by the new fossils and analyses indicate a close association between Tibetan Plateau uplift and diversification of the earliest living cats. PMID- 24225469 TI - Documenting reality. PMID- 24225467 TI - Sexual conflict over mating in red-sided garter snakes (Thamnophis sirtalis) as indicated by experimental manipulation of genitalia. AB - Sexual conflict over mating can result in sex-specific morphologies and behaviours that allow each sex to exert control over the outcome of reproduction. Genital traits, in particular, are often directly involved in conflict interactions. Via genital manipulation, we experimentally investigated whether genital traits in red-sided garter snakes influence copulation duration and formation of a copulatory plug. The hemipenes of male red-sided garter snakes have a large basal spine that inserts into the female cloaca during mating. We ablated the spine and found that males were still capable of copulation but copulation duration was much shorter and copulatory plugs were smaller than those produced by intact males. We also anaesthetized the female cloacal region and found that anaesthetized females copulated longer than control females, suggesting that female cloacal and vaginal contractions play a role in controlling copulation duration. Both results, combined with known aspects of the breeding biology of red-sided garter snakes, strongly support the idea that sexual conflict is involved in mating interactions in this species. Our results demonstrate the complex interactions among male and female traits generated by coevolutionary processes in a wild population. Such complexity highlights the importance of simultaneous examination of male and female traits. PMID- 24225470 TI - Caring for older lesbian, gay and bisexual people. AB - Ageing brings about a number of challenges for heterosexual, lesbian, gay and bisexual people. It can be a time of anxiety and concern. The expectations that many lesbian, gay and bisexual people have of how they would like to be cared for if they were to enter sheltered housing or other forms of residential care can be very different from the expectations of heterosexual people. This article considers issues that older lesbian, gay and bisexual people may encounter with regard to their health-care needs. PMID- 24225471 TI - Stoma complications: an overview. PMID- 24225472 TI - Unlicensed medicines: the right to prescribe 'specials' and the problem of overcharging. AB - The Government has announced an inquiry into alleged overcharging by wholesalers and pharmacists for the supply of unlicensed medicines known as 'specials'. This article explores what specials are, a district nurse's right to prescribe specials and why they are susceptible to gross overcharging in the NHS. PMID- 24225473 TI - Medication non-compliance in older patients: a multifactorial problem. PMID- 24225474 TI - The missing link: district nurses as social connection for older people with type 2 diabetes mellitus. AB - The relationship between social connection and health is widely recognised. However, there is a paucity of literature regarding the impact of district nursing care on social connection for people with a chronic illness such as type 2 diabetes mellitus (T2DM). Using a mixed-method approach, an exploration of the perceptions of older people living in the community with T2DM regarding their health and social connections was carried out. Findings revealed a strong relationship between the clients and the district nurse. The district nurse is an important aspect of clients' social connection. For some clients where their social connection is limited, the district nurse is a central element. When the district nurse is the major social connection, problems can arise for the client, especially when they are being discharged or changes are made to their care. PMID- 24225475 TI - Effect of home-based nursing pulmonary rehabilitation on patients with chronic obstructive pulmonary disease: a randomised clinical trial. AB - Fatigue is a common symptom of patients with chronic obstructive pulmonary disease (COPD), and results in a reduction of daily activity and quality of life in patients with the disease. The authors aimed to identify the effect of home based nursing pulmonary rehabilitation on fatigue, activities of daily living (ADL) and quality of life (QOL) in patients with COPD. A block randomisation method was used to randomise participants into case and control groups. Fatigue, ADL and QOL were assessed before and after the intervention in both groups. Independent and paired t-tests, chi-squared tests and covariance analysis were used to analysing data. Findings showed the significant decrease in the mean scores of fatigue (p<0.001) and significant improvement in mean scores of ADL (p<0.001) and QOL (p<0.001) after home-based nursing pulmonary rehabilitation in the case group. Home-based nursing pulmonary rehabilitation can be an effective, inexpensive and accessible programme for decreasing fatigue and improving ADL and QOL for patients with COPD. PMID- 24225476 TI - District nursing: the hidden giant of the NHS? AB - The recent 65th birthday of the NHS is a reminder of the purpose of the NHS: to provide a service that puts people that need it at the heart of care. However, recent negative reports have questioned nurses' ability to provide this care, which led to the development of the 6Cs. This article examines each of these values from the viewpoint of the district nursing service, in particular from a district nurse's perspective, as well as providing a critical commentary regarding the future of the service. PMID- 24225477 TI - Recurrent urinary tract infection in older women: an evidence-based approach. AB - Ageing increases the risk of a woman developing a urinary tract infection (UTI). It also increases the risk of misdiagnosis and inappropriate antibiotic therapy being prescribed. Antibiotic therapy has costs as well as benefits and can lead to changes in gut and vaginal flora that further predispose older women to UTI. Antibiotic resistance is growing and those who do have a UTI may experience treatment failure because of resistance to commonly used antibiotics. Accurate diagnosis and effective evidence-based treatment becomes even more crucial in the face of an ageing population and increasing antimicrobial resistance. Furthermore, the need for specific evidence-based guidelines for UTI in older people is increasing. PMID- 24225478 TI - Managing competing philosophies with palliative care. PMID- 24225479 TI - Optimising resources and medication management. PMID- 24225480 TI - k Opioids inhibit tumor angiogenesis by suppressing VEGF signaling. AB - Opioids are effective analgesics for the management of moderate to severe cancer pain. Here we show that kappa opioid receptor (KOR) agonists act as anti angiogenic factors in tumors. Treatment with KOR agonists, U50,488H and TRK820, significantly inhibited human umbilical vein endothelial cell (HUVEC) migration and tube formation by suppressing VEGFR2 expression. In contrast, treatment with a MU opioid receptor agonist, DAMGO, or a delta opioid receptor agonist, SNC80, did not prevent angiogenesis in HUVECs. Lewis lung carcinoma (LLC) or B16 melanoma grafted in KOR knockout mice showed increased proliferation and remarkably enhanced tumor angiogenesis compared with those in wild type mice. On the other hand, repeated intraperitoneal injection of TRK820 (0.1-10 MUg/kg, b.i.d.) significantly inhibited tumor growth by suppressing tumor angiogenesis. These findings indicate that KOR agonists play an important role in tumor angiogenesis and this knowledge could lead to a novel strategy for cancer therapy. PMID- 24225481 TI - Oxidized high-density lipoprotein induces the proliferation and migration of vascular smooth muscle cells by promoting the production of ROS. AB - AIM: As the major atheroprotective particle in plasma, high-density lipoprotein(HDL) is oxidized during atherosclerotic processes. Oxidized HDL(ox HDL) may lose its cardioprotective properties and develop a proinflammatory and proatherogenic phenotype. The proliferation and migration of vascular smooth muscle cells(VSMCs) play a crucial role in atherogenesis. However, the influence of ox-HDL on VSMC proliferation and migration remains poorly understood. METHODS: VSMCs were treated with native HDL(N-HDL) or ox-HDL at varying concentrations for different time intervals and used in several analyses. The degree of cell proliferation was assayed using CCK-8 kits. The level of cell migration was determined using a Transwell chamber and scratch-wound assay. The presence of intracellular reactive oxygen species(ROS) was detected based on ROS-mediated 2',7'-dichlorofluorescein fluorescence. The activation of NADPH oxidase was measured in terms of the Rac1 activity and NADP(+)/NADPH ratio. RESULTS: Compared to N-HDL, ox-HDL significantly promoted VSMC proliferation and migration in a dose-dependent manner. In addition, ox-HDL remarkably activated NADPH oxidase and enhanced ROS generation in the VSMCs. Diphenyleneiodonium chloride, an inhibitor of NADPH oxidase, and N-acetylcysteine, a ROS scavenger, efficiently inhibited the ROS production triggered by ox-HDL and subsequently blocked the proliferating and migrating effects of ox-HDL in the VSMCs. CONCLUSIONS: Ox-HDL significantly induces VSMC proliferation and migration by promoting NADPH oxidase activation and ROS production. Furthermore, the inhibition of NADPH oxidase and ROS generation blocks the proliferation and migration of VSMCs induced by ox-HDL. These proliferating and migrating effects of ox-HDL are closely related to its proinflammatory and proatherogenic roles. PMID- 24225483 TI - Thrombin activatable fibrinolysis inhibitor (TAFI): more complex when it meets the clot. PMID- 24225482 TI - Spike timing-dependent selective strengthening of single climbing fibre inputs to Purkinje cells during cerebellar development. AB - Shaping functional neural circuits in developing brain involves activity dependent refinement of early-formed redundant synapses. In the developing cerebellum, a one-to-one connection between a climbing fibre (CF) and a Purkinje cell (PC) is established by selective strengthening of a single CF followed by elimination of surplus CFs. Here we investigate developmental changes in CF mediated responses in PCs by using in vivo whole-cell recordings and two-photon Ca(2+) imaging. We show that each neonatal PC receives temporally clustered inputs from multiple CFs and temporal integration of these inputs is required to induce burst spiking and Ca(2+) rise in PCs. Importantly, a single CF input closest to PC's spike output is selectively strengthened during postnatal development. This spike timing-dependent selective strengthening is much less prominent in PC-selective P/Q-type voltage-dependent Ca(2+) channel knockout mice. Thus, spike timing- and Ca(2+)-dependent plasticity appears to underlie the selection of a single 'winner' CF and the establishment of mature CF-PC connections. PMID- 24225484 TI - Clinical outcome of surgically treated low-grade gliomas: a retrospective analysis of a single institute. AB - OBJECTIVE: Low grade gliomas (LGGs) are slow-growing primary brain tumors with heterogeneous clinical behaviors. The aim of our study is to review the treatment outcome of 63 patients with LGGs focusing on surgical outcome and the current therapeutic strategy. METHODS: We retrospectively enrolled 63 patients surgically treated for LGGs. The gross total resection (GTR) was performed in 35 patients (60.3%), subtotal resection (STR) was performed in 19 patients (31.7%) and partial resection (PR) or biopsy was performed in 9 patients (14.3%). We analyzed their progression-free survival (PFS), overall survival (OS), and malignant transformation with regard to age, gender, Karnofsky performance score (KPS), clinical presentation, tumor location, radiologic pattern, contrast enhancement, extent of removal, pathologic subtype, chemotherapy (CT) and radiotherapy (RT) treatment. RESULTS: Among all LGGs, the 3-year OS rate was 80% and the 5-year OS was 76%. The 3-year PFS rate was 83.6% and the 5-year PFS was 25%. The non eloquent area location showed a longer PFS than the eloquent area location (p=0.05). Oligodendroglial pathology showed a longer PFS compared to oligoastrocytomas and astrocytomas (p=0.02). Patients older than 60 years had poorer OS than younger patients (p<0.05). Female gender had a shorter OS than male gender (p<0.05), and a KPS of 90 or 100 had a longer OS than a KPS of 80 (p<0.05). Oligodendroglial pathology statistically correlated with a longer OS (p<0.05). CONCLUSION: The findings from our study, which were confirmed by uni- and multivariate analyses, demonstrated that radical tumor resection was associated with better long-term outcomes and tumor progression for patients with LGG. PMID- 24225485 TI - High-density array analysis of DNA methylation in Tamoxifen-resistant breast cancer cell lines. AB - Roughly two-thirds of all breast cancers are ERalpha-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understanding of Tamoxifen-resistance and identify novel pathways and targets of aberrant methylation, DNA from MCF-7 breast cancer cells and Tamoxifen-resistant derivatives, TMX2-11 and TMX2-28, were analyzed using the Illumina HumanMethylation450 BeadChip. Normalizing against MCF-7 values, ERalpha-positive TMX2-11 had 4000 hypermethylated sites and ERalpha negative TMX2-28 had over 33 000. Analysis of CpG sites altered in both TMX2-11 and TMX2-28 revealed that the Tamoxifen-resistant cell lines share 3000 hypermethylated and 200 hypomethylated CpGs. ZNF350 and MAGED1, two genes hypermethylated in both cell lines, were examined in greater detail. Treatment with 5-aza-2?deoxycitidine caused a significant reduction in promoter methylation of both ZNF350 and MAGED1 and a corresponding increase in expression in TMX2-28. A similar relationship between methylation and expression was not detected in TMX2-11. Our findings are indicative of the variable responses to methylation targeted breast cancer therapy and highlight the need for biomarkers that accurately predict treatment outcome. PMID- 24225487 TI - Recent advances in the medical management of Takayasu arteritis: an update on use of biologic therapies. AB - PURPOSE OF REVIEW: To critically review recent advances in medical management of Takayasu arteritis, with a special focus on the rationale and evidence to support the use of biologic agents in this disease. RECENT FINDINGS: Multiple case series and observational studies support the use of anti-tumor necrosis factor (TNF) medications, in particular infliximab, in patients who relapse upon tapering steroids and/or adding nonbiologic immunosuppressive agents. However, these medications must be continued to maintain effect, and often patients require increased doses over time. Tocilizumab and rituximab have been shown to lead to improved disease activity in small numbers of Takayasu's patients, including those refractory to anti-TNF treatment. SUMMARY: Anti-TNF agents are recommended for the treatment of Takayasu's patients who are unable to taper prednisone despite treatment with a nonbiologic immunosuppressive medication. Whether these biologic agents should be considered earlier in the treatment algorithm of these complicated patients remains an area of interest. Tocilizumab and rituximab may also be of benefit in refractory patients. Prospective randomized controlled trials are needed to confirm these findings. PMID- 24225488 TI - Retest imaging of [11C]NOP-1A binding to nociceptin/orphanin FQ peptide (NOP) receptors in the brain of healthy humans. AB - [(11)C]NOP-1A is a novel high-affinity PET ligand for imaging nociceptin/orphanin FQ peptide (NOP) receptors. Here, we report reproducibility and reliability measures of binding parameter estimates for [(11)C]NOP-1A binding in the brain of healthy humans. After intravenous injection of [(11)C]NOP-1A, PET scans were conducted twice on eleven healthy volunteers on the same (10/11 subjects) or different (1/11 subjects) days. Subjects underwent serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (one- and two tissue) modeling in large regions and by simpler regression methods (graphical Logan and bilinear MA1) in both large regions and voxel data. Retest variability and intraclass correlation coefficient (ICC) of VT were determined as measures of reproducibility and reliability respectively. Regional [(11)C]NOP-1A uptake in the brain was high, with a peak radioactivity concentration of 4-7 SUV (standardized uptake value) and a rank order of putamen>cingulate cortex>cerebellum. Brain time-activity curves fitted well in 10 of 11 subjects by unconstrained two-tissue compartmental model. The retest variability of VT was moderately good across brain regions except cerebellum, and was similar across different modeling methods, averaging 12% for large regions and 14% for voxel based methods. The retest reliability of VT was also moderately good in most brain regions, except thalamus and cerebellum, and was similar across different modeling methods averaging 0.46 for large regions and 0.48 for voxels having gray matter probability >20%. The lowest retest variability and highest retest reliability of VT were achieved by compartmental modeling for large regions, and by the parametric Logan method for voxel-based methods. Moderately good reproducibility and reliability measures of VT for [(11)C]NOP-1A make it a useful PET ligand for comparing NOP receptor binding between different subject groups or under different conditions in the same subject. PMID- 24225489 TI - A multiple kernel learning approach to perform classification of groups from complex-valued fMRI data analysis: application to schizophrenia. AB - FMRI data are acquired as complex-valued spatiotemporal images. Despite the fact that several studies have identified the presence of novel information in the phase images, they are usually discarded due to their noisy nature. Several approaches have been devised to incorporate magnitude and phase data, but none of them has performed between-group inference or classification. Multiple kernel learning (MKL) is a powerful field of machine learning that finds an automatic combination of kernel functions that can be applied to multiple data sources. By analyzing this combination of kernels, the most informative data sources can be found, hence providing a better understanding of the analyzed learning task. This paper presents a methodology based on a new MKL algorithm (nu-MKL) capable of achieving a tunable sparse selection of features' sets (brain regions' patterns) that improves the classification accuracy rate of healthy controls and schizophrenia patients by 5% when phase data is included. In addition, the proposed method achieves accuracy rates that are equivalent to those obtained by the state of the art lp-norm MKL algorithm on the schizophrenia dataset and we argue that it better identifies the brain regions that show discriminative activation between groups. This claim is supported by the more accurate detection achieved by nu-MKL of the degree of information present on regions of spatial maps extracted from a simulated fMRI dataset. In summary, we present an MKL-based methodology that improves schizophrenia characterization by using both magnitude and phase fMRI data and is also capable of detecting the brain regions that convey most of the discriminative information between patients and controls. PMID- 24225486 TI - Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology. AB - In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005. PMID- 24225490 TI - The diagnosis and molecular analysis of a novel 21.9kb deletion (Qinzhou type deletion) causing alpha+ thalassemia. AB - alpha-Thalassemia is a common single-gene genetic disease that can cause Hb Bart's hydrops fetalis and Hb H disease in tropical and subtropical regions. When examining conventional thalassemia genes, an only detected --(SEA) genotype sample needs further analysis. In doing so, we found a novel 21.9kb deletion (Qinzhou type deletion). The deletion position of the novel 21.9kb deletion is from 14373bp to 36299bp of the alpha-globin gene cluster (NG_000006.1); thus, there exists a 21927bp sequence deletion, into which a 29bp sequence is added. After sequence analysis, a group of Gap-PCR primers were synthesized to diagnose this novel thalassemia genotype. Through pedigree analysis, we deduced that the propositus obtained the novel alleles from her mother. The genotype of this propositus is --(SEA)/-alpha(21.9) and its phenotype conforms to the characteristics of Hb H disease, establishing that the combination between alpha(21.9) genotype and alpha(0) genotype can lead to Hb H disease. By molecular analysis, we established that this case fits the characteristic of an alpha(+) thalassemia genotype. PMID- 24225491 TI - Synchronous occurrence of colon adenocarcinoma and gastric schwannoma: case report and review of the literature. AB - MATERIAL OF STUDY: We report a case of a 66-year-old man with a gastric schwannoma incidentally discovered during the treatment of a colon cancer. At the pre-operative computed tomography performed for the stadiation of the colonic tumor was incidentally noted the presence of a nodular tumor between the liver and the gastric wall. RESULT: A wedge resection of this gastic tumor and the surgical resection of the left colon were performed all at once. The pathological examination of the gastric neoplasia revealed a picture consistent with gastric schwannoma. DISCUSSION: Gastrointestinal schwannomas are difficult but not impossible to diagnose preoperatively although they are often asymptomatic and radiologic findings are often nonspecific. Radiological features of Gastrointestinal schwannomas described in literature are reviewed. CONCLUSIONS: The treatment of choice is complete surgical excision with free margins because of diagnostic uncertainty, and the long-term outcome is excellent as these lesions are uniformly benign. PMID- 24225492 TI - Thiocholine mediated stabilization of in situ produced CdS quantum dots: application for the detection of acetylcholinesterase activity and inhibitors. AB - The use of acetylcholinesterase (AChE) inhibitors as chemical warfare agents or pesticides represents a strong hazard against human health. The high toxicity of these compounds arises from their ability to inhibit acetylcholinesterase from degrading acetylcholine (ACh), which could affect the physiology of the nervous system with serious or fatal consequences. Here we report a simple and fluorimetric system for a highly sensitive detection of AChE activity and inhibitors. The principle of this approach is based on the hydrolysis of acetylthiocholine (ATCh) by AChE, which yields the thiol-bearing compound thiocholine (TCh) that at trace concentrations stabilized the in situ generated CdS quantum dots (QDs). The system shows a linear relationship between the fluorescence intensity and AChE activity from 1 to 10 mU mL(-1) in buffer solution. The accuracy of the proposed system was further demonstrated through the determination of AChE activity in human serum (HS) by the standard addition method. Furthermore, this novel and highly sensitive sensing system allows the detection of 80 pM of the AChE inhibitor paraoxon and 100 nM of galanthamine. The reported methodology shows potential applications for the development of a simple and inexpensive assay for the routine quantification of AChE activity and inhibitors. PMID- 24225493 TI - Work, work-life conflict and health in an industrial work environment. AB - BACKGROUND: Work-life conflict has been poorly studied as a cause of ill-health in occupational medicine. AIMS: To study associations between physical and psychosocial working conditions, including work-life conflict on the one hand and general, physical and mental health outcomes on the other. METHODS: Cross sectional data were used from an employee survey among the workforces of four medium-sized and large companies in Switzerland. Physical work factors included five demands and exposures such as heavy loads, repetitive work and poor posture. Psychosocial factors included 14 demands and limited resources such as time pressure, overtime, monotonous work, job insecurity, low job autonomy, low social support and work-life conflict. Health outcomes studied were self-rated health, sickness absence, musculoskeletal disorders, sleep disorders, stress and burnout. RESULTS: There was a response rate of 49%; 2014 employees participated. All adverse working conditions were positively associated with several poor health outcomes in both men and women. After mutual adjustment for all work factors and additional covariates, only a few, mainly psychosocial work factors remained significant as risk factors for health. Work-life conflict, a largely neglected work-related psychosocial factor in occupational medicine, turned out to be the only factor that was significantly and strongly associated with all studied health outcomes and was consistently found to be the strongest or second strongest of all the studied risk factors. CONCLUSIONS: Even in an industrial work environment, psychosocial work factors, and particularly work-life conflict, play a key role and need to be taken into consideration in research and workplace health promotion. PMID- 24225494 TI - Zoledronate attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of Rho/ROCK-dependent JNK and NF-kappaB pathway. AB - AIMS: Abdominal aortic aneurysm (AAA) is a life-threatening disease affecting almost 10% of the population over the age of 65. Nitrogen-containing bisphosphonates (N-BPs) have been shown to exert anti-atherogenic and anti angiogenic effects, but the potential effects of N-BPs on AAA remain unclear. Here, we tested whether a potent N-BP, zoledronate, can attenuate the formation of Angiotensin II (Ang II)-induced AAA in hyperlipidaemic mice. METHODS AND RESULTS: Low-density lipoprotein receptor(-/-) (LDLR(-/-)) mice infused for 28 days with Ang II were treated with placebo and 100 MUg/kg/day zoledronate. Continuous Ang II infusion in LDLR(-/-) mice exhibited a 59% incidence of AAA formation, and treatment with zoledronate decreased AAA formation (21%). Compared with the saline group, administration of zoledronate in Ang II-infused LDLR(-/-) mice attenuated the expansion of the suprarenal aorta (maximal aortic diameter), reduced elastin degradation in the media layer of the aorta, and significantly diminished vascular inflammation by reduction in vascular cell adhesion molecule expression and macrophage accumulation. Treatment with zoledronate decreased matrix metalloproteinase-2 (MMP-2) in aortic tissues. Zoledronate-treated mice had significant down-regulation of JNK, NF-kappaB, and reduced Ang II-induced Rho/ROCK activation. Zoledronate reduced monocytes adherence to human aortic endothelial cells in vitro. CONCLUSION: Zoledronate-attenuated Ang II induced AAA formation by suppression of MMP-2 activity and suppressed vascular inflammation and Ang II-induced Rho/ROCK activities. PMID- 24225495 TI - Au25 clusters as electron-transfer catalysts induced the intramolecular cascade reaction of 2-nitrobenzonitrile. AB - Design of atomically precise metal nanocluster catalysts is of great importance in understanding the essence of the catalytic reactions at the atomic level. Here, for the first time, Au25(z) nanoslusters were employed as electron transfer catalysts to induce an intramolecular cascade reaction at ambient conditions and gave rise to high conversion (87%) and selectivity (96%). Electron spin-resonance spectra indeed confirmed the consecutive electron transfer process and the formation of N radical. UV-vis absorption spectra also verified Au25(z) was intact after the catalytic circle. Our research may open up wide opportunities for extensive organic reactions catalyzed by Au25(z). PMID- 24225496 TI - Biological dose assessment after low-dose overexposures in nuclear medicine. AB - This paper focuses on the application of dicentric chromosome assay biodosimetry in cases of low-dose overexposures to professionals working in nuclear medicine and discusses how to present the results and associated uncertainties, to make possible a better understanding of biodosimetric reports. Five examples are presented of low or possibly zero exposure dose that are illustrative of typical problems that arise in occupational settings, in this instance in nuclear medicine departments. This is a scenario of minor concern in terms of health consequences but it is relevant in legal terms. They pose dilemmas for investigators but biological dosimetry can make a valuable contribution to resolving the cases. PMID- 24225497 TI - Pathology caused by persistent murine norovirus infection. AB - Subclinical infection of murine norovirus (MNV) was detected in a mixed breeding group of WT and Stat1(-/-) mice with no outward evidence of morbidity or mortality. Investigations revealed the presence of an attenuated MNV variant that did not cause cytopathic effects in RAW264.7 cells or death in Stat1(-/-) mice. Histopathological analysis of tissues from WT, heterozygous and Stat1(-/-) mice revealed a surprising spectrum of lesions. An infectious molecular clone was derived directly from faeces (MNV-O7) and the sequence analysis confirmed it was a member of norovirus genogroup V. Experimental infection with MNV-O7 induced a subclinical infection with no weight loss in Stat1(-/-) or WT mice, and recapitulated the clinical and pathological picture of the naturally infected colony. Unexpectedly, by day 54 post-infection, 50 % of Stat1(-/-) mice had cleared MNV-O7. In contrast, all WT mice remained infected persistently. Most significantly, this was associated with liver lesions in all the subclinically infected WT mice. These data confirmed that long-term persistence in WT mice is established with specific variants of MNV and that despite a subclinical presentation, active foci of acute inflammation persist within the liver. The data also showed that STAT1-dependent responses are not required to protect mice from lethal infection with all strains of MNV. PMID- 24225498 TI - IL-10 encoded by viruses: a remarkable example of independent acquisition of a cellular gene by viruses and its subsequent evolution in the viral genome. AB - Many viruses have evolved strategies to deregulate the host immune system. These strategies include mechanisms to subvert or recruit the host cytokine network. IL 10 is a pleiotropic cytokine that has both immunostimulatory and immunosuppressive properties. However, its key features relate mainly to its capacity to exert potent immunosuppressive effects. Several viruses have been shown to upregulate the expression of cellular IL-10 (cIL-10) with, in some cases, enhancement of infection by suppression of immune functions. Other viruses encode functional orthologues of cIL-10, called viral IL-10s (vIL-10s). The present review is devoted to these virokines. To date, vIL-10 orthologues have been reported for 12 members of the family Herpesviridae, two members of the family Alloherpesviridae and seven members of the family Poxviridae. Study of vIL 10s demonstrated several interesting aspects on the origin and the evolution of these viral genes, e.g. the existence of multiple (potentially up to nine) independent gene acquisition events at different times during evolution, viral gene acquisition resulting from recombination with cellular genomic DNA or cDNA derived from cellular mRNA and the evolution of cellular sequence in the viral genome to restrict the biological activities of the viral orthologues to those beneficial for the virus life cycle. Here, various aspects of the vIL-10s described to date are reviewed, including their genetic organization, protein structure, origin, evolution, biological properties and potential in applied research. PMID- 24225499 TI - Entry of influenza A virus: host factors and antiviral targets. AB - Influenza virus is a major human pathogen that causes annual epidemics and occasional pandemics. Moreover, the virus causes outbreaks in poultry and other animals, such as pigs, requiring costly and laborious countermeasures. Therefore, influenza virus has a substantial impact on health and the global economy. Here, we review entry of this important pathogen into target cells, an essential process by which viral genomes are delivered from extracellular virions to sites of transcription/replication in the cell nucleus. We summarize current knowledge on the interaction of influenza viruses with their receptor, sialic acid, and highlight the ongoing search for additional receptors. We describe receptor mediated endocytosis and the recently discovered macropinocytosis as alternative virus uptake pathways, and illustrate the subsequent endosomal trafficking of the virus with advanced live microscopy techniques. Release of virus from the endosome and import of the viral ribonucleoproteins into the host cell nucleus are also outlined. Although a focus has been on viral protein function during entry, recent studies have revealed exciting information on cellular factors required for influenza virus entry. We highlight these, and discuss established entry inhibitors targeting viral and host factors, as well as the latest prospects for designing novel 'anti-entry' compounds. New entry inhibitors are of particular importance for current efforts to develop the next generation of anti influenza drugs - entry is the first essential step of virus replication and is an ideal target to block infection efficiently. PMID- 24225500 TI - High pressure synthesis, structure, and multiferroic properties of two perovskite compounds Y2FeMnO6 and Y2CrMnO6. AB - High purity crystals of Y2FeMnO6 (YFMO) and Y2CrMnO6 (YCMO) have been synthesized for the first time using a flux method under a high temperature of 1573 K and high pressure of 6 GPa. Both YFMO and YCMO have orthorhombic structures in space group Pnma. The temperature-dependent magnetization and the nonlinear M-H hysteresis loops of both materials indicate that an antiferromagnetic transition occurs at the Neel temperature of 328 K for YFMO, and a ferrimagnetic transition occurs at 74 K for YCMO. YFMO is a relaxor ferroelectric in which three dielectric relaxations were observed at 245, 328 and 358 K, respectively. The first relaxation process is due to Maxwell-Wagner polarization at the grain boundary whereas the second and the third relaxation behaviours arise from the beginning and the ending of antiferromagnetic ordering, respectively. The presence of the dielectric anomaly near TN indicates the magnetoelectric effect. Ferroelectric hysteresis loops and PUND (positive-up & negative-down) pulse data reveal weak ferroelectric behavior of YFMO at 77 K. Otherwise one dielectric constant anomaly has been found for YCMO at about 390 K. But no ferroelectric polarization was observed in YCMO. PMID- 24225501 TI - Reduced expression of prostacyclin synthase and nitric oxide synthase in subcutaneous arteries of type 2 diabetic patients. AB - Diabetic endothelial dysfunction is characterized by impaired endothelium dependent relaxation. In this study, we measured the expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS), and prostacyclin receptor (IP) in subcutaneous arteries of type-2 diabetic and non-diabetic patients. Subcutaneous arteries were dissected from tissues from seven diabetics (4 males and 3 females) and seven non diabetics (5 males and 2 females) aged between 18 to 65 years, who underwent lower limb surgical procedures. Diabetics had higher fasting blood glucose compared to non-diabetics, but there were no differences in blood pressure, body mass index and age. Patients were excluded if they had uncontrolled hypertension, previous myocardial infarction, coronary heart disease, renal or hepatic failure and tumor. The relative expression levels of eNOS, COX-1, COX-2, PGIS and IP receptor were determined by Western blotting analysis, normalized with the beta actin level. Increased expression of COX-2 was observed in subcutaneous arteries of diabetics compared to non-diabetics, whereas the expression levels of eNOS and PGIS were significantly lower in diabetics. There were no significant differences in expression levels of COX-1 and IP receptor between the two groups. Immunohistochemical study of subcutaneous arteries showed that the intensities of eNOS and PGIS staining were lower in diabetics, with higher COX-2 staining. In conclusion, type-2 diabetes is associated with higher COX-2 expression, but lower eNOS and PGIS expression in subcutaneous arteries. These alterations may lead to impaired endothelium-dependent vasodilatation, and thus these proteins may be potential targets for protection against the microvascular complications of diabetes. PMID- 24225502 TI - Evolution in management and outcome after repair of abdominal aortic aneurysms in the pre- and post-EVAR era. AB - OBJECTIVE: To compare outcomes of abdominal aortic aneurysm repairs before and after the endovascular era. METHODS: Group A (1997-1998) included 331 patients, 321 (97%) with open repair (OR) and 10 (3%) with endovascular aneurysm repair (EVAR). Group B (2007-2008) included 330 patients, 136 (41%) with OR and 194 (59%) with EVAR. RESULTS: Patients in Group B were older (74 +/- 8.5 vs 73 +/- 7.0 years, P = .02), had higher comorbidity scores (8.3 +/- 4.8 vs 7.5 +/- 4.6, P = .04), shorter hospitalization (5.1 +/- 6.4 vs 9.8 +/- 6.3, P < .001), less intensive care unit days than in Group B (0.9 +/- 2.1 vs 2.2 +/- 2.7, P < .001). Early mortality was 0.6% in both groups. Two-year survival was similar (88% vs 89%), with less reinterventions in Group A (4% vs 17%, P = .004). OR patients had similar 30-day mortalities (0.9% vs 0.7%, P = .89). CONCLUSION: EVAR and OR have low mortalities. However, in the post-EVAR era we treat older patients with more comorbidities, hospitalization is shorter, and intensive care unit days are less; interventions in EVAR are, however, high. PMID- 24225503 TI - Variability in the management of superficial venous thrombophlebitis among phlebologists and vascular surgeons. AB - INTRODUCTION: This study aimed to compare management patterns of patients with superficial venous thrombophlebitis (SVT) among phlebologists and vascular surgeons. METHODS: A survey was provided to practitioners who attended the American Venous Forum meeting in 2011. Statistical analysis included descriptive statistics, unpaired t tests, and Friedman's test for correlation. RESULTS: There were 354 US or Canadian health care providers of whom 169 were phlebologists and 185 were vascular surgeons. There was a significant different in anticoagulation administration and duration (P = .034, P = .032, respectively). Friedman's test for correlation between multiple surgical treatments showed no correlation between surgical treatments tested with all treatments having an equal distribution in our data. Follow-up differed between groups with vascular surgeons following up with imaging more than phlebologists (P = .03). CONCLUSION: Our data indicate that there is no consensus between or among phlebologists or vascular surgeons as to the surgical management of superficial venous thrombophlebitis, duration of follow-up, and anticoagulation parameters. PMID- 24225504 TI - Stent fracture in the superficial femoral and proximal popliteal arteries: literature summary and economic impacts. AB - OBJECTIVES: To summarize available evidence regarding stent fracture in the femoropopliteal region. METHODS: We searched PubMed, 2000-2011, using MeSH search terms "stents," "popliteal artery," and "femoral artery." RESULTS: We identified 29 original studies reporting 0% to 65% incidence of stent fracture. Fracture related repeat revascularization could be avoided in the absence of device failure. Recently published data suggest that even a 5% rate of fracture-related reintervention would generate $118.4 million in health care cost in the United States. These excess procedures would also result in major complications and deaths that might have been avoided in the absence of stent fracture. CONCLUSIONS: Reported incidence and clinical relevance of femoropopliteal stent fractures vary across studies. Stent fracture may lead to repeat revascularization. These reinterventions create considerable--and potentially avoidable--economic burden for patients and payers. Further, these costs are effectively invisible wherever stent fractures are not systematically documented as the reason for reintervention. PMID- 24225505 TI - Pressure ulcers in Jordan: a snapshot survey of a tertiary public hospital. AB - BACKGROUND: Patients are at risk of developing pressure ulcers while they are hospitalised. These risks need to be managed effectively to avoid harm and to minimise costs. OBJECTIVE: This study was aimed at determining the prevalence and incidence of pressure ulcers at selected acute clinical settings in central Jordan. DESIGN: A cross-sectional survey design. METHOD: An inpatient snapshot survey was conducted over 4 weeks in the two medical wards in a tertiary public hospital. RESULTS: 190 participants were surveyed, 30 cases were identified, 53% were male, and 75% were aged 60 years or older. Prevalence was 24%, approximately half of the cases were grade 2 and 23% were grade 3 and 4. Pressure ulcers were mainly found on the sacrum (43%), followed by the heel (24%). Over 4 weeks, 29 new pressure ulcer cases were identified; 55% were male, and 90% were aged 60 years or older. Pressure ulcers were mainly-in 38% of cases-identified with cerebral vascular accident patients. CONCLUSION: The results of the snapshot survey confirmed that there is a problem with maintaining patients' safety in terms of patients acquiring pressure ulcers in hospital. The number of pressure ulcers indicate less-than-optimal management of patient safety, which requires a more detailed investigation. PMID- 24225506 TI - Preregistration nurses' views on the delivery of tissue viability. AB - This article outlines an evaluation of preregistration nursing students' views on the delivery of tissue viability during their preregistration education in preparation for registration with the Nursing and Midwifery Council (NMC, 2010). Data were collected from two cohorts of preregistration (n=170) over a 2-year period by means of interactive voting keypads. The author concludes that preregistration preparation within the university was inadequate for both the prevention and provision of tissue viability care in clinical practice. PMID- 24225508 TI - Wound infection conundrum. PMID- 24225507 TI - Reducing hospital-acquired pressure damage: an NHS acute trust initiative. AB - During 2009, Maidstone and Tunbridge Wells NHS Trust reviewed its pressure ulcer prevention strategy; this included patient interventions and equipment provision. Standard hospital mattresses were requiring replacement and dynamics were used frequently, while the overall prevalence of pressure damage remained high. Replacing the standard foam mattress with a non-powered pressure-redistributing system (AtmosAir) was proposed. The rationale for this was that by renewing all standard foam mattresses with the AtmosAir 4000, all patients would have immediate access to a pressure redistributing mattress. Training and education of staff was increased and the Trust redesigned documentation. The outcome of this approach was a significant reduction in hospital-acquired pressure damage. PMID- 24225509 TI - Patient care and management: reduced skin integrity of the foot. AB - The development and deterioration of pressure ulcers are a frequent occurrence across all healthcare settings and specialties, posing daily challenges to the healthcare worker and unnecessary suffering to the patient. Reduced skin integrity occurs within those patients deemed high risk, particularly to the vulnerable areas such as the heel and ankle (American Physical Therapy Association (APTA), 1996). The incidence of pressure ulcers, alongside diabetes, vascular insufficiency and obesity, is on the increase, posing additional demands on current clinical resources; specialist clinics, debridement therapies and appropriate dressing management regimes. This article will focus on the heel and ankle in regards to reduced skin integrity and the positive introduction of an innovative dressing product as an adjunct to the overall care and management of this patient group. PMID- 24225510 TI - Removing all barriers: a 10-patient evaluation in the acute care setting. AB - Wound bed preparation is an essential component of care in the management of wounds where healing is delayed. The removal of devitalised tissue quickly and safely may present as a challenge to clinicians. Drawtex Hydroconductive Dressing with LevaFiber Technology was evaluated within an acute hospital on a range of wounds and was shown to effectively prepare the wound bed. The speed and cost of debridement observed in this small group of patients was remarkable and suggests that this dressing can play an essential part in the wound healing process. PMID- 24225511 TI - Interrater reliability of the Glamorgan scale: overt and covert data. AB - The Glamorgan Paediatric Pressure Ulcer Risk Assessment Scale (Glamorgan scale) had been developed using statistical analysis of patient data. The aim of this study was to assess the reliability of the Glamorgan scale using overt and covert methods. METHOD: For the overt data collection, randomly selected trained nursing staff were invited to participate. Twenty-seven trained nursing staff assessed 27 children and young people within 10 minutes of an assessment by the researcher. For the covert part of the data collection the researcher and the paediatric tissue viability (TV) link nurse risk assessed inpatients on wards and units where the overt data collection had taken place, their findings were compared with the last recorded assessment by the clinical nurses. RESULTS: In the overt data collection 24 out of 27 nurses agreed with the researcher (88.9% agreement, kappa 0.867). In the covert data collection, 41 out of 55 risk assessments had been completed. Of the 41 completed assessments 34 agreed with the researcher and tissue viability link nurse (82.9% agreement, kappa 0.763). CONCLUSION: The level of agreement was good for overt and covert interrater reliability data. PMID- 24225512 TI - Hand burn management: minimising pain and trauma at dressing change. AB - The aim of wound management in hand burn injuries is to restore function and prevent problem scars, so a key consideration in wound healing is the removal of dressings without causing pain and further trauma as well as preserving function. Conventionally, wound dressings such as paraffin gauze were used for burn injuries, but this led to pain and trauma on removal, as well as drying out. This study looks at the use of Mepitel(r) One on hand burns; this dressing incorporates all the benefits of Mepitel, however, it only has Safetac technology on the wound contact side, allowing easy handling and application. PMID- 24225513 TI - The role of barrier protection ain pressure ulcer prevention. AB - This article considers the anatomy and physiology of the skin, the natural protection the skin provides in relation to barrier protection and the importance of barrier protection in pressure ulcer prevention. The current national pressure ulcer agenda including high impact actions and the SSKIN care bundle, along with their implementation within one NHS Health Care Trust are discussed. PMID- 24225514 TI - Martyn Butcher. PMID- 24225515 TI - ACSM clinician profile. PMID- 24225516 TI - Preventing exertional sickling deaths: the right way, the wrong way, and the Army way. PMID- 24225518 TI - Behavioral modification to reduce concussion in collision sports: ice hockey. PMID- 24225519 TI - Exaggerated pain after injury in the athlete: complex regional pain considerations. PMID- 24225520 TI - Recurrent exertional rhabdomyolysis: coincidence, syndrome, or acquired myopathy? AB - The purposes of this report are to review and discuss the issue of recurrent exertional rhabdomyolysis (ER), the return to physical activity after ER, and the possible causes of recurrence, with special consideration to metabolic myopathies and the possibility of an acquired post-ER myopathy. We discuss the medical investigation required prior to return to physical activity after an episode of ER and suggest two possible mechanisms for recurrence of ER in the absence of a known cause: premature return to activity and an acquired post-ER muscular disorder. We also emphasize the need to create proper guidelines for return to physical activity after ER and, for further investigation, the possible mechanisms of ER recurrence in patients without a known metabolic myopathy. PMID- 24225521 TI - Use of graded exercise testing in concussion and return-to-activity management. AB - Concussion is a physiologic brain injury that produces systemic and cognitive symptoms. The metabolic and physiologic changes of concussion result in altered autonomic function and control of cerebral blood flow. Evaluation and treatment approaches based upon the physiology of concussion may therefore add a new dimension to concussion care. In this article, we discuss the use of a standard treadmill test, the Buffalo Concussion Treadmill Test (BCTT), in acute concussion and in postconcussion syndrome (PCS). The BCTT has been shown to diagnose physiologic dysfunction in concussion safely and reliably, differentiate it from other diagnoses (e.g., cervical injury), and quantify the clinical severity and exercise capacity of concussed patients. It is used in PCS to establish a safe aerobic exercise treatment program to help speed recovery and return to activity. The use of a provocative exercise test is consistent with world expert consensus opinion on establishing physiologic recovery from concussion. PMID- 24225522 TI - Helmets in sport: fact and fallacy. AB - Head injuries and the prevention of both the short-term and long-term consequences have received heightened awareness in recent years. Education and legislative efforts have promoted both appropriate treatment of concussion and pushed the use of helmets for protection from head injuries. Current scientific data would suggest that helmets are effective at decreasing the risk of serious head injuries. However there is no evidence to suggest that helmets are protective against concussive injuries or the long-term impact of repetitive head trauma. PMID- 24225523 TI - Injuries in professional football: current concepts. AB - Professional football is one of the most popular sports in the United States. There is a common constellation of injuries that are seen frequently. Much attention has been focused on concussions and their long-term outcomes in this population. Other common causes of morbidity include cervical spine injuries, knee injuries including anterior cruciate ligament and other ligamentous injuries, ankle sprains, and medical issues including cardiac and sickle trait. Several recent studies have focused on hip impingement and hamstring injuries, among others, as sources of missed playing time as well. This review describes some of the frequently seen injuries and medical issues in professional football players. Proper management of both medical disease and on-field injuries can reduce morbidity and may lead to faster return to play and reduced risk of future injury. PMID- 24225524 TI - Medical issues in synchronized skating. AB - Synchronized skating is a unique sport of team skating and currently represents the largest competitive discipline in U.S. Figure Skating. Synchronized skating allows skaters to compete as part of a team with opportunities to represent their country in international competitions. As the popularity of the sport continues to grow, more of these athletes will present to sports medicine clinics with injuries and illnesses related to participation in synchronized skating. The purpose of this article is to review the common injuries and medical conditions affecting synchronized skaters. PMID- 24225525 TI - Athletes and the arts--the role of sports medicine in the performing arts. AB - Performing artists are athletes. Like athletes, performing artists practice and/or perform most days with little off season, play through pain, "compete" in challenging environments, and risk career-threatening injury. Athletes and the Arts is a multiorganizational initiative linking the sport athlete and musician/performing artist communities. Performing artists of all ages and genre are an underserved population related to medical coverage, care, injury prevention, performance enhancement, and wellness. Sports medicine professionals are a valuable resource for filling this gap by applying existing knowledge of treating sport athletes (nutrition, injury prevention) while gaining a better understanding of performers' unique needs (hearing loss, focal dystonia) and environment. These applications can occur in the clinical setting and through developing organizational policies. By better understanding the needs of the performing arts population and applying existing concepts and knowledge, sports medicine professionals can expand their impact to a new patient base that desperately needs support. PMID- 24225526 TI - Anterior knee pain in the active and athletic adolescent. AB - Anterior knee pain (or patellofemoral pain) continues to be a source of frustration and confusion among clinicians. There is wide variation in symptom history, physical exam findings, imaging, and treatment that often confounds the use of any straightforward algorithm or decision tree. This review aims to provide an approach that partners the adolescent athlete with clinician and an experienced physiotherapist. This team approach uses available evidence to develop a treatment program that is specific to the adolescent's symptoms, body movement patterns, and activity demands. PMID- 24225527 TI - Prolonged perioperative surgical prophylaxis within European hospitals: an exercise in uncertainty avoidance? AB - OBJECTIVES: Socio-cultural factors have been hypothesized to be important drivers for inappropriate antibiotic prescribing in ambulatory care. This study sought to assess any potential role in perioperative surgical prophylaxis (PAP) administered for >24 h (PAP > 24). Within hospitals, PAP continues to be administered for longer than 24 h, despite unequivocal evidence of ineffectiveness beyond this period. A recently published European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) has reported that in 70% of participating countries, PAP > 24 was administered in more than half of the surgical operations surveyed. METHODS: Correlation and simple linear regression modelling was performed using the PAP > 24 proportions for the countries in the ECDC PPS report and the respective scores for the cultural construct of uncertainty avoidance (UA), as detailed by Hofstede. RESULTS: Pearson correlation analysis produced a moderately strong coefficient (r) of 0.50 (95% CI 0.16-0.74; P = 0.007). Simple regression yielded a model of PAP > 24 = 29.87 + 0.40UA (R(2) = 0.25; P = 0.007). CONCLUSIONS: Cultural factors, namely UA, appear to be an important driver for PAP > 24. Any strategy aimed at improving prolonged PAP should be informed by clear knowledge of local socio cultural barriers, so as to achieve the most successful intervention possible. PMID- 24225528 TI - Ultralow field NMR spectrometer with an atomic magnetometer near room temperature. AB - We present a Cs atomic magnetometer with a sensitivity of 150fT/Hz(1/2) operating near room temperature. The nuclear magnetic resonance (NMR) signal of 125MUL tap water was detected at an ultralow magnetic field down to 47nT, with the signal-to noise ratio (SNR) of the NMR signal approaching 50 after eight averages. Relaxivity experiments with a Gd(DTPA) contrast agent in zero field were performed, in order to show the magnetometer's ability to measure spin-lattice relaxation time with high accuracy. This demonstrates the feasibility of an ultralow field NMR spectrometer based on a Cs atomic magnetometer, which has a low working temperature, short data acquisition time and high sensitivity. This kind of NMR spectrometer has great potential in applications such as chemical analysis and magnetic relaxometry detection in ultralow or zero fields. PMID- 24225530 TI - Job strain and hypertension. PMID- 24225529 TI - Resolution and measurement of heteronuclear dipolar couplings of a noncrystalline protein immobilized in a biological supramolecular assembly by proton-detected MAS solid-state NMR spectroscopy. AB - Two-dimensional (15)N chemical shift/(1)H chemical shift and three-dimensional (1)H-(15)N dipolar coupling/(15)N chemical shift/(1)H chemical shift MAS solid state NMR correlation spectra of the filamentous bacteriophage Pf1 major coat protein show single-site resolution in noncrystalline, intact-phage preparations. The high sensitivity and resolution result from (1)H detection at 600MHz under 50kHz magic angle spinning using ~0.5mg of perdeuterated and uniformly (15)N labeled protein in which the exchangeable amide sites are partially or completely back-exchanged (reprotonated). Notably, the heteronuclear (1)H-(15)N dipolar coupling frequency dimension is shown to select among (15)N resonances, which will be useful in structural studies of larger proteins where the resonances exhibit a high degree of overlap in multidimensional chemical shift correlation spectra. PMID- 24225531 TI - Eremophila glabra reduces methane production and methanogen populations when fermented in a Rusitec. AB - Eremophila glabra Juss. (Scrophulariaceae), a native Australian shrub, has been demonstrated to have low methanogenic potential in a batch in vitro fermentation system. The present study aimed to test longer-term effects of E. glabra on rumen fermentation characteristics, particularly methane production and the methanogen population, when included as a component of a fermentation substrate in an in vitro continuous culture system (Rusitec). E. glabra was included at 150, 250, 400 g/kg DM (EG15, EG25, and EG40) with an oaten chaff and lupin-based substrate (control). Overall, the experiment lasted 33 days, with 12 days of acclimatization, followed by two periods during which fermentation characteristics (total gas, methane and VFA productions, dry matter disappearance, pH) were measured. The number of copies of genes specifically associated with total bacteria and cellulolytic bacteria (16S rRNA gene) and total ruminal methanogenic archaeal organisms (the methyl coenzyme M reductase A gene (mcrA)) was also measured during this time using quantitative real-time PCR. Total gas production, methane and volatile fatty acid concentrations were significantly reduced with addition of E. glabra. At the end of the experiment, the overall methane reduction was 32% and 45% for EG15 and EG25 respectively, compared to the control, and the reduction was in a dose-dependent manner. Total bacterial numbers did not change, but the total methanogen population decreased by up to 42.1% (EG40) when compared to the control substrate. The Fibrobacter succinogenes population was reduced at all levels of E. glabra, while Ruminococcus albus was reduced only by EG40. Our results indicate that replacing a portion of a fibrous substrate with E. glabra maintained a significant reduction in methane production and methanogen populations over three weeks in vitro, with some minor inhibition on overall fermentation at the lower inclusion levels. PMID- 24225532 TI - Hierarchically macro-mesoporous Pt/gamma-Al2O3 composite microspheres for efficient formaldehyde oxidation at room temperature. AB - Room temperature catalytic oxidation by noble metals is considered to be the most promising strategy for the removal of HCHO, which is one of the major indoor air pollutants. Hierarchically macro-mesoporous structured Pt/gamma-Al2O3 hollow spheres with open and accessible pores were synthesized and used for catalytic oxidative decomposition of HCHO at room temperature. The prepared composite hollow spheres showed higher catalytic activity than the conventional nanoparticle supports, which is mainly due to their hierarchical macro-mesoporous structure facilitating diffusion of reactants and products, and the high dispersion of accessible catalytic Pt nanoparticles. This work may contribute to the development of hierarchically structured materials and high-performance catalysts for indoor air purification and related catalytic processes. PMID- 24225534 TI - Bronchoalveolar lavage fluid in Standardbred racehorses: influence of unilateral/bilateral profiles and cut-off values on lower airway disease diagnosis. AB - The aim of this study was to determine whether the lung side being sampled would significantly influence bronchoalveolar lavage (BAL) cytological profiles and subsequent diagnosis in Standardbred racehorses. One hundred and thirty-eight French Trotters in active training and racing were included in a prospective observational study. BAL was performed using videoendoscopy in both right and left lungs during summer meetings in 2011 (64 horses) and 2012 (74 horses). Cytological data performed 24h later from right and left lungs were compared and specifically used to classify horses as affected with exercise-induced pulmonary haemorrhage (EIPH), inflammatory airway disease (IAD), or were 'controls'. For IAD, cytological definition was based on two different cut off values. Neutrophil percentages, haemosiderophage percentages and the haemosiderophage/macrophage (H/M) ratios were significantly higher in the right compared to the left lung. Measures of intra-class correlation coefficients revealed a fair agreement between left and right lungs for percentages of mast cells, eosinophils, and for the H/M ratio, and a moderate agreement for neutrophil percentages. Fair to moderate agreements were observed between left and right lungs for the diagnosis of IAD and/or EIPH based on kappa coefficients. When sampling one lung only, the risk of incorrectly classifying a horse as a 'control' increased with the use of the restraint cut-off values for IAD. As BAL from one lung is not representative of the other lung in the same horse, both lungs should be sampled for a better assessment of lung cellularity and for a precise diagnosis of lower airway diseases. PMID- 24225533 TI - Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid beta secretion via deregulated lysosomal exocytosis. AB - Alzheimer's disease (AD) belongs to a category of adult neurodegenerative conditions, which are associated with intracellular and extracellular accumulation of neurotoxic protein aggregates. Understanding how these aggregates are formed, secreted and propagated by neurons has been the subject of intensive research, but so far no preventive or curative therapy for AD is available, and clinical trials have been largely unsuccessful. Here we show that deficiency of the lysosomal sialidase NEU1 leads to the spontaneous occurrence of an AD-like amyloidogenic process in mice. This involves two consecutive events linked to NEU1 loss-of-function--accumulation and amyloidogenic processing of an oversialylated amyloid precursor protein in lysosomes, and extracellular release of Abeta peptides by excessive lysosomal exocytosis. Furthermore, cerebral injection of NEU1 in an established AD mouse model substantially reduces beta amyloid plaques. Our findings identify an additional pathway for the secretion of Abeta and define NEU1 as a potential therapeutic molecule for AD. PMID- 24225536 TI - Aberrant synchrony in the somatosensory cortices predicts motor performance errors in children with cerebral palsy. AB - Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices. PMID- 24225537 TI - Human stretch reflex pathways reexamined. AB - Reflex responses of tibialis anterior motor units to stretch stimuli were investigated in human subjects. Three types of stretch stimuli were applied (tap like, ramp-and-hold, and half-sine stretch). Stimulus-induced responses in single motor units were analyzed using the classical technique, which involved building average surface electromyogram (SEMG) and peristimulus time histograms (PSTH) from the discharge times of motor units and peristimulus frequencygrams (PSF) from the instantaneous discharge rates of single motor units. With the use of SEMG and PSTH, the tap-like stretch stimulus induced five separate reflex responses, on average. With the same single motor unit data, the PSF technique indicated that the tap stimulus induced only three reflex responses. Similar to the finding using the tap-like stretch stimuli, ramp-and-hold stimuli induced several peaks and troughs in the SEMG and PSTH. The PSF analyses displayed genuine increases in discharge rates underlying the peaks but not underlying the troughs. Half-sine stretch stimuli induced a long-lasting excitation followed by a long-lasting silent period in SEMG and PSTH. The increase in the discharge rate, however, lasted for the entire duration of the stimulus and continued during the silent period. The results are discussed in the light of the fact that the discharge rate of a motoneuron has a strong positive linear association with the effective synaptic current it receives and hence represents changes in the membrane potential more directly and accurately than the other indirect measures. This study suggests that the neuronal pathway of the human stretch reflex does not include inhibitory pathways. PMID- 24225538 TI - Shape selectivity and remapping in dorsal stream visual area LIP. AB - We explore the visual world by making rapid eye movements (saccades) to focus on objects and locations of interest. Despite abrupt retinal image shifts, we see the world as stable. Remapping contributes to visual stability by updating the internal image with every saccade. Neurons in macaque lateral intraparietal cortex (LIP) and other brain areas update information about salient locations around the time of a saccade. The depth of information transfer remains to be thoroughly investigated. Area LIP, as part of the dorsal visual stream, is regarded as a spatially selective area, yet there is evidence that LIP neurons also encode object features. We sought to determine whether LIP remaps shape information. This knowledge is important for understanding what information is retained from each glance. We identified 82 remapping neurons. First, we presented shapes within the receptive field and tested for shape selectivity in a fixation task. Among the remapping neurons, 28 neurons (34%) were selective for shape. Second, we presented the same shapes in the future location of the receptive field around the time of the saccade and tested for shape selectivity during remapping. Thirty-one (38%) neurons were selective for shape. Of 11 neurons that were shape selective in both tasks, 5 showed significant correlation between shape selectivity in the two tasks. Across the population, there was a weak but significant correlation between responses to shape in the two tasks. Our results provide neurophysiological evidence that remapped responses in area LIP can encode shape information as well as spatial information. PMID- 24225539 TI - Activation of group I metabotropic glutamate receptors enhances persistent sodium current and rhythmic bursting in main olfactory bulb external tufted cells. AB - Rhythmically bursting olfactory bulb external tufted (ET) cells are thought to play a key role in synchronizing glomerular network activity to respiratory driven sensory input. Whereas spontaneous bursting in these cells is intrinsically generated by interplay of several voltage-dependent currents, bursting strength and frequency can be modified by local intrinsic and centrifugal synaptic input. Activation of metabotropic glutamate receptors (mGluRs) engages a calcium-dependent cation current (I(CAN)) that increases rhythmic bursting, but mGluRs may also modulate intrinsic mechanisms involved in bursting. Here, we used patch-clamp electrophysiology in rat olfactory bulb slices to investigate whether mGluRs modulate two key intrinsic currents involved in ET cell burst initiation: persistent sodium (I(NaP)) and hyperpolarization activated cation (Ih) currents. Using a BAPTA-based internal solution to block I(CAN), we found that the mGluR1/5 agonist DHPG enhanced I(NaP) but did not alter Ih. I(NaP) enhancement consisted of increased current at membrane potentials between -60 and -50 mV and a hyperpolarizing shift in activation threshold. Both effects would be predicted to shorten the interburst interval. In agreement, DHPG modestly depolarized (~3.5 mV) ET cells and increased burst frequency without effect on other major burst parameters. This increase was inversely proportional to the basal burst rate such that slower ET cells exhibited the largest increases. This may enable ET cells with slow intrinsic burst rates to pace with faster sniff rates. Taken with other findings, these results indicate that multiple neurotransmitter mechanisms are engaged to fine-tune rhythmic ET cell bursting to context- and state-dependent changes in sniffing frequency. PMID- 24225540 TI - Differential requirement for NMDAR activity in SAP97beta-mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses. AB - PSD-95-like, disc-large (DLG) family membrane-associated guanylate kinase proteins (PSD/DLG-MAGUKs) are essential for regulating synaptic AMPA receptor (AMPAR) function and activity-dependent trafficking of AMPARs. Using a molecular replacement strategy to replace endogenous PSD-95 with SAP97beta, we show that the prototypic beta-isoform of the PSD-MAGUKs, SAP97beta, has distinct NMDA receptor (NMDAR)-dependent roles in regulating basic properties of AMPAR containing synapses. SAP97beta enhances the number of AMPAR-containing synapses in an NMDAR-dependent manner, whereas its effect on the size of unitary synaptic response is not fully dependent on NMDAR activity. These effects contrast with those of PSD-95alpha, which increases both the number of AMPAR-containing synapses and the size of unitary synaptic responses, with or without NMDAR activity. Our results suggest that SAP97beta regulates synaptic AMPAR content by increasing surface expression of GluA1-containing AMPARs, whereas PSD-95alpha enhances synaptic AMPAR content presumably by increasing the synaptic scaffold capacity for synaptic AMPARs. Our approach delineates discrete effects of different PSD-MAGUKs on principal properties of glutamatergic synaptic transmission. Our results suggest that the molecular diversity of PSD-MAGUKs can provide rich molecular substrates for differential regulation of glutamatergic synapses in the brain. PMID- 24225541 TI - Cortical regulation of dopaminergic neurons: role of the midbrain superior colliculus. AB - Dopaminergic (DA) neurons respond to stimuli in a wide range of modalities, although the origin of the afferent sensory signals has only recently begun to emerge. In the case of vision, an important source of short-latency sensory information seems to be the midbrain superior colliculus (SC). However, longer latency responses have been identified that are less compatible with the primitive perceptual capacities of the colliculus. Rather, they seem more in keeping with the processing capabilities of the cortex. Given that there are robust projections from the cortex to the SC, we examined whether cortical information could reach DA neurons via a relay in the colliculus. The somatosensory barrel cortex was stimulated electrically in the anesthetized rat with either single pulses or pulse trains. Although single pulses produced small phasic activations in the colliculus, they did not elicit responses in the majority of DA neurons. However, after disinhibitory intracollicular injections of the GABAA antagonist bicuculline, collicular responses were substantially enhanced and previously unresponsive DA neurons now exhibited phasic excitations or inhibitions. Pulse trains applied to the cortex led to phasic changes (excitations to inhibitions) in the activity of DA neurons at baseline. These were blocked or attenuated by intracollicular administration of the GABAA agonist muscimol. Taken together, the results indicate that the cortex can communicate with DA neurons via a relay in the SC. As a consequence, DA neuronal activity reflecting the unexpected occurrence of salient events and that signaling more complex stimulus properties may have a common origin. PMID- 24225543 TI - Normalization of input patterns in an associative network. AB - Numerous brain structures have a cerebellum-like architecture in which inputs diverge onto a large number of granule cells that converge onto principal cells. Plasticity at granule cell-to-principal cell synapses is thought to allow these structures to associate spatially distributed patterns of granule cell activity with appropriate principal cell responses. Storing large sets of associations requires the patterns involved to be normalized, i.e., to have similar total amounts of granule cell activity. Using a general model of associative learning, we describe two ways in which granule cells can be configured to promote normalization. First, we show how heterogeneity in firing thresholds across granule cells can restrict pattern-to-pattern variation in total activity while also limiting spatial overlap between patterns. These effects combine to allow fast and flexible learning. Second, we show that the perceptron learning rule selectively silences those synapses that contribute most to pattern-to-pattern variation in the total input to a principal cell. This provides a simple functional interpretation for the experimental observation that many granule cell to-Purkinje cell synapses in the cerebellum are silent. Since our model is quite general, these principles may apply to a wide range of associative circuits. PMID- 24225544 TI - Predictive control of ankle stiffness at heel contact is a key element of locomotor adaptation during split-belt treadmill walking in humans. AB - Split-belt treadmill walking has been extensively utilized as a useful model to reveal the adaptability of human bipedal locomotion. While previous studies have clearly identified different types of locomotor adaptation, such as reactive and predictive adjustments, details of how the gait pattern would be adjusted are not fully understood. To gain further knowledge of the strategies underlying split belt treadmill adaptation, we examined the three-dimensional ground reaction forces (GRF) and lower limb muscle activities during and after split-belt treadmill walking in 22 healthy subjects. The results demonstrated that the anterior component of the GRF (braking force) showed a clear pattern of adaptation and subsequent aftereffects. The muscle activity in the tibialis anterior muscle during the early stance phase was associated with the change of braking force. In contrast, the posterior component of GRF (propulsive force) showed a consistent increase/decrease in the fast/slow leg during the adaptation period and was not followed by subsequent aftereffects. The muscle activity in the gastrocnemius muscle during the stance phase gradually decreased during the adaptation phase and then showed a compensatory reaction during the washout phase. The results indicate that predictive feedforward control is required to set the optimal ankle stiffness in preparation for the impact at the heel contact and passive feedback control is used for the production of reflexively induced propulsive force at the end of the stance phase during split-belt treadmill adaptation. The present study provides information about the detailed mechanisms underlying split-belt adaptation and should be useful for the construction of specific rehabilitation protocols. PMID- 24225542 TI - Association of COMT val158met and DRD2 G>T genetic polymorphisms with individual differences in motor learning and performance in female young adults. AB - Individuals learn new skills at different rates. Given the involvement of corticostriatal pathways in some types of learning, variations in dopaminergic transmission may contribute to these individual differences. Genetic polymorphisms of the catechol-O-methyltransferase (COMT) enzyme and dopamine receptor D2 (DRD2) genes partially determine cortical and striatal dopamine availability, respectively. Individuals who are homozygous for the COMT methionine (met) allele show reduced cortical COMT enzymatic activity, resulting in increased dopamine levels in the prefrontal cortex as opposed to individuals who are carriers of the valine (val) allele. DRD2 G-allele homozygotes benefit from a higher striatal dopamine level compared with T-allele carriers. We hypothesized that individuals who are homozygous for COMT met and DRD2 G alleles would show higher rates of motor learning. Seventy-two young healthy females (20 +/- 1.9 yr) performed a sensorimotor adaptation task and a motor sequence learning task. A nonparametric mixed model ANOVA revealed that the COMT val-val group demonstrated poorer performance in the sequence learning task compared with the met-met group and showed a learning deficit in the visuomotor adaptation task compared with both met-met and val-met groups. The DRD2 TT group showed poorer performance in the sequence learning task compared with the GT group, but there was no difference between DRD2 genotype groups in adaptation rate. Although these results did not entirely come out as one might predict based on the known contribution of corticostriatal pathways to motor sequence learning, they support the role of genetic polymorphisms of COMT val158met (rs4680) and DRD2 G>T (rs 1076560) in explaining individual differences in motor performance and motor learning, dependent on task type. PMID- 24225545 TI - Sensory feedback to ankle plantar flexors is not exaggerated during gait in spastic hemiplegic children with cerebral palsy. AB - It is still widely believed that exaggerated stretch reflexes and increased muscle tone in ankle plantar flexors contribute to reduced ankle joint movement during gait in children with cerebral palsy (CP). However, no study has directly measured stretch reflex activity during gait in these children. We investigated sensory feedback mechanisms during walking in 20 CP children and 41 control children. Stretch responses in plantar flexor muscles evoked in stance showed an age-related decline in control but not CP children. In swing the responses were abolished in control children, but significant responses were observed in 14 CP children. This was related to reduced activation of dorsiflexors in swing. Removal of sensory feedback in stance produced a drop in soleus activity of a similar size in control and CP children. Soleus activity was observed in swing to the same extent in control and CP children. Removal of sensory feedback in swing caused a larger drop in soleus activity in control children than in CP children. The lack of age-related decline in stretch reflexes and the inability to suppress reflexes in swing is likely related to lack of maturation of corticospinal control in CP children. Since soleus activity was not seen more frequently than in control children in swing and since sensory feedback did not contribute more to their soleus activity, spasticity is unlikely to contribute to foot drop and toe walking. We propose that altered central drive to the ankle muscles and increased passive muscle stiffness are the main causes of foot drop and toe walking. PMID- 24225546 TI - Amplified plasmonic detection of DNA hybridization using doxorubicin-capped gold particles. AB - We show in this article that doxorubicin-modified gold nanoparticles (Au NP-DOX) can be used for the post-amplification of the wavelength shift of localized surface plasmon resonance (LSPR) signals after DNA hybridization events. We take advantage of the intercalation properties of DOX with guanine-rich oligonucleotides and the plasmon coupling between surface-linked gold nanostructures and Au NP-DOX in solution to detect in a sensitive manner DNA hybridisation events. Post-treatment of double-stranded DNA with Au NP-DOX resulted in a detection limit of ~600 pM, several times lower than that without post-incubation (LOD ~ 40 nM). PMID- 24225547 TI - Redressing the public image of general practice. PMID- 24225548 TI - The rise of health coaching. PMID- 24225549 TI - Holding children and young people: defining skills for good practice. AB - Physical holds are used to help children and young people receive clinical care in situations where their behaviour may limit the ability of nurses and allied professionals to deliver treatment effectively. This article provides an overview of a qualitative study of 11 nurses and allied professionals who were interviewed with semi-structured questions. The major findings suggest there is a lack of clear and agreed terminology and nurses and allied professionals are guessing at how to describe the practice. As a result, there was no discussion or documentation of the practices of holding (whether successful or unsuccessful) within the clinical area. For the last decade, professional opinion was that this is an 'uncontested practice'. It can therefore be questioned whether this practice has moved from being 'uncontested' to 'indifferent'. Nurses and allied professionals need to revive a common definition of 'good' around the actions of holding, which can hopefully lead to holding skills being more clearly defined and evidence-based. PMID- 24225550 TI - Integrative health care: implications for nursing practice and education. AB - The significance of complementary and alternative medicine (CAM) to contemporary health care is reflected in the relatively recent integrative health care (IHC) movement. Having emerged in response to the public's sustained use of CAM, IHC reflects the evolving needs and expectations of modern-day service users, making it consistent with today's culture of patient-responsive health care. IHC therefore carries important implications for nursing practice but, to fulfil their responsibilities with regard to these implications, nurses need a fundamental knowledge of CAM concepts as well as an understanding of the ways in which CAM and conventional health care might affect one another. An educational strategy that embeds IHC and makes explicit its relation to nursing practice is desirable if nurses are to engage with patients who use CAM. Evidence suggests, however, that neither CAM nor IHC are adequately represented in nursing curricula. This paper considers ways in which IHC could be incorporated into nursing curricula as a means to prepare nurses for this important challenge. PMID- 24225551 TI - Perioperative simulation learning and post-registration development. AB - Competence to practise in the perioperative environment requires specialist knowledge (Gillespie and Hamlin, 2009). Newly qualified staff in this environment can experience difficulty in making the transition into practice (Stratton, 2011) and often feel overwhelmed by the skills required (Callaghan, 2010). Simulation based learning techniques are increasingly used by practice educators specifically within these environments (Cato and Murray, 2010) to aid with acquisition of skills, emergency care delivery, general post-registration development and also as a standardised indicator of 'competence' (Bullock et al, 2008; Cato and Murray, 2010). This article will consider the impact of this educational strategy on the learner's lifelong development following registration, and its position in relation to the widely accepted learning paradigms of Benner's 'Novice to Expert' and Maslow's 'Hierarchy of Needs'. Through discussion of the nature of education in the practice setting, the reader will be prompted to reconsider the actual value of simulation-based learning in the post-registration arena and how this may be used to redefine simulation in the clinical setting. PMID- 24225552 TI - Knowing Generation Y: a new generation of nurses in practice. AB - Generation Y is commonly defined as those people born between 1980 and 2000, now aged in their 20s and 30s. Their grandparents experienced post-World War II reconstruction, their parents the economic boom of the 1980s. There are currently 81 million individuals in the Generation Y cohort in the USA, making it the second-largest, and possibly most influential, cohort since World War II (Manion, 2009). Members of Generation Y are diverse, technologically advanced and vocal about their opinions. They tend to resist traditional hierarchy, want recognition/reward for achievements and distrust institutions. Knowing these characteristics is useful for nurse managers, preceptors and team members working with members of Generation Y. Studies have proven that Generation Y is challenging the nursing workforce through rapid turnover (Cogin, 2012). This article explores a theoretical model that predicts retention and/or turnover of nurses in light of Generation Y behaviours and motivators-for example, moving from agency to agency rather than devoting many years to a single practice. Further research is needed to find out whether these behaviours and motivators are unique to Generation Y alone. PMID- 24225553 TI - Integrated health care for patients with motor neurone disease. AB - This article presents the findings from a study trip to Kaiser Permanente (KP), a private healthcare provider in the USA. The aim of the trip was to understand how healthcare integration is managed in KP and how this might help patients in the UK with motor neurone disease (MND). This article makes reference to the American and British healthcare systems, identifying the simple differences between health economies, and their impact on health care, with specific reference to MND. The trip was undertaken as part of the author's ongoing work on how patients with MND rate services delivered by the multidisciplinary team (MDT) in the UK. The author's community matron role involves caring for patients with long-term conditions (LTCs) including long-term neurological conditions (LTNCs). In executing this role and in service delivery to patients with LTNCs, specifically MND, the author noticed a lack of robust integration, highlighting the need to consider and address the various contributory factors. This article presents a literature review and analyses the role of the MDT including specialist neurological professionals in executing duties and in delivering healthcare services to patients diagnosed with MND. The implications for practice are also presented along with areas for practice development. PMID- 24225554 TI - Extending the scope of wilful neglect will result in paternalistic nursing care. AB - The recommendation that the criminal offence of wilful neglect be extended to protect all patient groups may seem a proactive way for the Government to begin to restore public confidence in nursing following the Mid Staffordshire NHS Trust Inquiry. However, the experience of the courts hearing cases of wilful neglect in relation to adults who lack capacity show that they are complex trials and, despite several appeals, still lack clear guidance that nurses can apply in practice to avoid prosecution while still promoting the autonomy of patients. In this article the author reviews recent cases of wilful neglect to come before the Court of Appeal and argues that rather than offering protection to patients, criminalising a failure to act is more likely to result in paternalistic interventions, with nurses insisting on providing care because they fear prosecution if they fail to do so. PMID- 24225555 TI - A simple guide to the Research Excellence Framework. PMID- 24225557 TI - Clinical supervision: from staff nurse to nurse consultant. Part 8: confidentiality and records. PMID- 24225556 TI - The House of Commons Health Committee reports on Francis. PMID- 24225558 TI - Engaging with NMC revalidation. PMID- 24225559 TI - BiOI/TiO2 nanotube arrays, a unique flake-tube structured p-n junction with remarkable visible-light photoelectrocatalytic performance and stability. AB - A series of unique flake-tube structured p-n heterojunctions of BiOI/TiO2 nanotube arrays (TNTAs) were successfully prepared by loading large amounts of BiOI nanoflakes onto both the outer and inner walls of well-separated TiO2 nanotubes using anodization followed by the sequential chemical bath deposition (S-CBD) method. The as-prepared BiOI/TNTAs samples were characterized by X-ray diffraction, electron microscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy and nitrogen sorption. The photoelectrocatalytic (PEC) activity and stability of the BiOI/TNTAs samples toward degradation of methyl orange (MO) solutions under visible-light irradiation (lambda > 420 nm) were evaluated. The visible-light PEC performance of BiOI/TNTAs samples was further confirmed by the transient photocurrent response test. The results from the current study revealed that the 5-BiOI/TNTAs sample exhibited the best PEC activity, favourable stability, and the highest photocurrent density among all the BiOI/TNTAs heterostructured samples. The combined effects of several factors may contribute to the remarkable visible-light PEC performance for the 5 BiOI/TNTAs sample including a 3D connected intertube spacing system and an open tube-mouth structure, strong visible-light absorption by BiOI, the formation of a p-n junction, larger specific surface area, and the impact of the applied external electrostatic field. PMID- 24225561 TI - Probing kojic acid binding to tyrosinase enzyme: insights from a model complex and QM/MM calculations. AB - An unambiguous picture of the interaction between the inhibitor kojic acid and a model of the dicopper active site of tyrosinase is reported. The observed binding mode probed on bacterial enzyme is confirmed and further refined by QM/MM calculations. PMID- 24225560 TI - Oral L-arginine before resistance exercise blunts growth hormone in strength trained males. AB - Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 +/- 4 y; body mass: 81.4 +/- 9.0 kg; height: 179.4 +/- 6.9 cm; and training experience: 6.3 +/- 3.4 y) participated in a randomized double blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g.kg-1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 +/- 368.7 vs. placebo = 487.9+/- 482.0 min.ng.mL1, p < .05). L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop. PMID- 24225562 TI - [A case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody without anti-myelin-associated glycoprotein (MAG) activity]. AB - We report a case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody. An 84-year old man complained of numbness on the left side of the face and in the distal portions of the limbs. Neurological examination showed mild sensory ataxia. The laboratory tests revealed the presence of IgM lambda paraproteinemia and anti-SGPG IgG antibody without anti-myelin-associated glycoprotein (MAG) activity and anti-MAG/SGPG IgM antibody. Results of nerve conduction study showed decreased sensory nerve action potential (SNAP) amplitude, indicating the presence of sensory-dominant axonal polyneuropathy, and the prolongation of distal latency was not observed. Treatment with corticosteroids resulted in a rapid improvement in neurological abnormalities. In IgM paraproteinemic neuropathy associated with anti-MAG/SGPG antibody, distal acquired demyelinating sensory neuropathy and resistance to immunological treatments are the characteristic pathologic and clinical features, respectively. On the other hand our rare case of IgM paraproteinemic neuropathy positive for anti-SGPG IgG antibody presented with axonal sensory polyneuropathy and a good responsiveness to corticosteroids. PMID- 24225563 TI - [Leptomeningeal infiltlation of primary CNS B-cell lymphoma diagnosed by the biopsy of cauda equina: a case report]. AB - A 49-year-old man was admitted to our hospital with progressive gait disturbance. Our examination revealed a low grade fever, weight loss derived muscle weakness, sensory disturbance and loss of deep tendon reflex of the lower extremities. Magnetic resonance imaging (MRI) detected an abnormal intensity and gadolinium enhancement in the cauda equina. Two weeks after admission, disturbance of consciousness and bladder appeared. Cerebrospinal fluid examination showed pleocytosis, elevated protein and soluble IL-2R, but cytological examination was class II negative. We performed a cauda equina biopsy urgently and diagnosed malignant lymphoma, of a diffuse large B-cell type. We selected combined MTX based chemoradiotherapy and his symptoms significantly improved after a month. He achieved complete remission and remains recurrence-free after 10 months post treatment although he remains with light paraparesis and sensory disturbance of the lower extremities. He has already gone back to a normal life. An examination of cauda equina biopsy led to quick diagnosis and treatment. PMID- 24225564 TI - [A case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with treatment-resistant status epilepticus that was effectively treated with lamotrigine]. AB - A 16-year-old woman with MELAS developed fever and myoclonic epilepsy which improved with conventional anti-epileptic drugs. Since seizures recurred one month after successful treatment, the doses of phenobarbital, clonazepan, and valproate were increased. However, there was no improvement and status epilepticus continued. The addition of lamotrigine resulted in a decreased frequency and good control of seizures. This case is important, showing satisfactory results from the addition of lamotrigine for treatment-resistant status epilepticus. PMID- 24225565 TI - [An autopsy case of Alzheimer's disease presenting with corticobasal syndrome]. AB - A right-handed Japanese man developed memory loss at 51 years of age. The right side clumsiness developed from 52 years of age and then progressively worsened. Temporal/parietal lobe atrophy was observed predominantly on the left side upon MR imaging. Subsequently, limb-kinetic apraxia and parkinsonism became apparent predominantly on the right side. These symptoms became aggravated along with dementia, ultimately leading to an apallic state. The patient eventually died at the age of 59 due to aspiration pneumonia. An autopsy was carried out and cerebral atrophy was observed predominantly on the left side. Senile plaques were observed on the entire cerebral cortex at a high frequency, along with many cotton wool plaques. Anti-phosphorylated tau-positive neurofibrillary tangles and several neuropil threads were observed upon immunostaining. The tau-positive structures were also positive for both RD3 and RD4 antibodies. The findings of tauopathy of the glia were poor, and the tau lesion of the brainstem was milder than that of the cerebral cortex. These results suggest the possibility that the corticobasal syndrome clinically developed in some type of Alzheimer's disease and a definite diagnosis was made only by pathological examination. PMID- 24225566 TI - [Neurosarcoidosis presenting with severe hyposmia and polyradiculopathy]. AB - A 50-year-old woman presented with constriction sensation in the lower part of the chest, paresthesia in the right forearm and hypesthesia in the right thigh. One month later, she noticed a loss of sense of smell. The normal findings of the nasal mucosa and the impaired results of standard olfactory acuity test (T&T olfactometry) and intravenous olfactory test (Alinamin test) suggested a lesion proximal to the nasal mucosa. Sensory disturbances in the segmental areas of cervical, thoracic and lumbar regions were clinically and electrophysiologically attributed to polyradiculopathy. MRI of the brain and whole spine revealed no abnormalities. Cerebrospinal fluid examination showed lymphocytic pleocytosis. Sarcoidosis was diagnosed based on the findings including an elevated serum angiotensin-converting enzyme level, bilateral hilar lymphadenopathy on the chest CT and histological evidence of noncaseating granulomas. Methylprednisolone pulse therapy improved the olfactory and sensory disturbances. Neurosarcoidosis should be considered in the differential diagnosis of olfactory impairment. PMID- 24225567 TI - [Streptococcus pneumoniae meningitis treated successfully with polymyxin B immobilized fiber therapy: a case report]. AB - A-61-year old man was admitted to our hospital with fever and severe disturbance of consciousness. He was diagnosed with Streptococcus pneumoniae meningitis on the basis of cerebrospinal fluid (CSF) analysis and urinary antigen detection by immunochromatography. Although he was treated with dexamethasone and antibiotics, his general status worsened as systemic inflammatory response syndrome (SIRS), disseminated intravascular coagulation (DIC), and status epileptics developed. Following treatment with polymyxin B-immobilized fiber therapy (PMX), which can also absorb bacteria-derived toxic substances, he recovered from DIC and SIRS, and disturbance of consciousness improved immediately. In addition, the concentration of several CSF cytokines--IL-1, IL-2, and TNF-alpha--was decreased. The present case suggests that PMX is a good option for severe bacterial meningitis. PMID- 24225568 TI - [Primary central nervous system lymphoma mimicking ventriculitis]. AB - A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, lambda+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis. PMID- 24225569 TI - [Intracranial germinoma masquerading as a granulomatous inflammation, diagnostic failure after brain biopsy]. AB - We report the case of a 33-year-old man with diplopia, sleepiness, and paresthesia of the left upper limb that were slowly progressive. On admission, he presented with restriction in the vertical movement of the eyes and abduction of the right eye, and horizontal and convergence nystagmus. Slight weakness of the left upper limb, bilateral Babinski sign, and truncal ataxia were also noted. Cerebral magnetic resonance imaging was performed, and gadolinium-enhanced T1 weighted imaging revealed a mass lesion that involved the diencephalon and the corpus callosum, which was invariably enhanced. Specimens obtained using a brain biopsy showed epithelioid granuloma with the presence of foreign body giant cells and lymphocytic infiltration. Prednisolone was administrated because we suspected neurosarcoidosis, but the clinical symptoms worsened with the enlargement of the lesion. A re-evaluation of the biopsy specimens using immunohistochemistry revealed tumor cells of germinoma that were scattered among the lymphocytes and positive for periodic acid-Schiff staining, placental alkaline phosphatase, and c kit. A combination of chemotherapy and radiation resulted in clinical improvement and marked reduction of the mass lesion in size. We concluded that the possibility of germinoma should be considered in case granulomatous inflammation is observed in brain biopsy specimens. PMID- 24225570 TI - []An adult case of mumps-associated encephalitis/encephalopathy successfully treated with steroid pulse therapy]. AB - A 32-year-old-immunologically healthy woman suffered from mumps. A few days later, she was brought to our hospital because of generalized convulsions. On arrival, she developed a decorticate posture. Anti-mumps virus antibodies were detected in her serum. Elevated protein levels without pleocytosis were observed in her cerebrospinal fluid. On the basis of a diagnosis of mumps-associated encephalitis/encephalopathy, steroid pulse therapy was administered, which improve her disturbance of consciousness. She exhibited akinetic mutism, which was followed by deterioration of the frontal lobe. Single-photon emission computed tomography demonstrated decreased regional cerebral blood flow in the bilateral frontal regions. Therefore, she was suspected with frontal lobe dysfunction associated with the lesion, including the thalamus and/or brain stem. We consider that the encephalitis/encephalopathy present in this case was caused by a reversible autoimmune process triggered by mumps virus infection. PMID- 24225571 TI - [Ineffective mefloquine therapy in progressive multifocal leukoencephalopathy complicated with malignant lymphoma: finding and usefulness of susceptibility weighted imaging]. AB - A 57-year-old woman presented with motor and cognitive impairments under treatment for cryptogenic organizing pneumonia with immunosuppressive agents. Magnetic resonance imaging showed widespread signal abnormalities in the cerebral white matter. Susceptibility-weighted imaging showed attenuated contrast of the cerebral medullary vein in the lesions, and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) revealed decreased uptake at the same site and increased uptake in multifocal lung involvements. Lung biopsy findings were consistent with diffuse large B-cell lymphoma. Polymerase chain reaction for JC Virus DNA in cerebrospinal fluid yielded positive results. Based on these findings, the present case was given a diagnosis of progressive multifocal leukoencephalopathy (PML). The patient was treated with oral mefloquine, but her respiratory condition deteriorated and chemotherapy was required to prevent further deterioration. As a result, chemotherapy to treat lymphoma could not result in beneficial immune reconstitution, PML continued to progress despite mefloquine treatment, and the patient developed decorticate posture. The efficacy of mefloquine in patients with non-HIV-associated PML warrants further investigation. PMID- 24225578 TI - Newly available antibodies with practical applications in surgical pathology. AB - Selected antibodies that have become available in recent years and have applications in diagnostic pathology are discussed. They include antibodies that are organ-related, provide information on cellular differentiation or histogenetic type, have predictive value in tumors, and highlight infective agents. PAX8 (paired box gene 8) is a marker expressed in the lower female genital tract, thyroid, and kidney and their tumors. Napsin A is expressed in the lung and kidney and is an alternative marker for pulmonary adenocarcinoma. Arginase A is a sensitive and specific marker for liver tumors. ERG (Ets-related gene) is an excellent marker for endothelium and vascular tumors as well as prostatic cancer (about 50% of cases). SOX10 (SRY-related HMG box) is expressed predominantly in melanocytic and Schwann cells and the corresponding tumors. DOG1 (discovered on GIST 1) is an excellent marker for gastrointestinal stromal tumor (GIST) and acinic cell carcinoma. OCT3/4 is a pan-germ cell tumor marker, except yolk sac tumor. SALL4 is positive in various types of germ cell tumors, including yolk sac tumor. MUC4 (mucin-related antigen 4) is a sensitive and specific marker for low-grade fibromyxoid sarcoma. Langerin is a specific marker for Langerhans cells and their tumors. SOX11 is a sensitive marker for mantle cell lymphoma. New generation antibodies against anaplastic lymphoma kinase (ALK) are required to reliably demonstrate ALK gene translocation in pulmonary carcinomas. Lack of expression of succinate dehydrogenase B is seen in paragangliomas of the hereditary form and in the pediatric type of GIST. Antibodies against Trepenoma pallidum can facilitate the diagnosis of syphilis, whereas those against SV40 (simian virus 40) are helpful for diagnosis of BK virus infection and progressive multifocal leukoencephalopathy. PMID- 24225579 TI - State residence restrictions and forcible rape rates: a multistate quasi experimental analysis of UCR data. AB - This study examines whether the presence of state residence restrictions resulted in changes in statewide rates of forcible rape. It builds on the limited geographic coverage of prior studies by including state-level Uniform Crime Report (UCR) data across 19 years for 49 states and the District of Columbia. It uses a quasi-experimental research method based on a longitudinal fixed-effects panel model design, which can help control for relatively static differences between states. Results indicate that when a state residence restriction was present, regardless of how it was measured, rates of UCR forcible rape were higher in the state than when the policy was not present. This suggests that residence restrictions, at least at the state level, are not useful as an overall crime prevention measure, but may be useful for increasing detection or reporting levels of such crimes. However, results also suggest that the size of the increase varied by whether the policy only applied to offenders with child victims or also included those with adult victims. Implications for research and policy are discussed. PMID- 24225580 TI - From protein sequence to dynamics and disorder with DynaMine. AB - Protein function and dynamics are closely related; however, accurate dynamics information is difficult to obtain. Here based on a carefully assembled data set derived from experimental data for proteins in solution, we quantify backbone dynamics properties on the amino-acid level and develop DynaMine--a fast, high quality predictor of protein backbone dynamics. DynaMine uses only protein sequence information as input and shows great potential in distinguishing regions of different structural organization, such as folded domains, disordered linkers, molten globules and pre-structured binding motifs of different sizes. It also identifies disordered regions within proteins with an accuracy comparable to the most sophisticated existing predictors, without depending on prior disorder knowledge or three-dimensional structural information. DynaMine provides molecular biologists with an important new method that grasps the dynamical characteristics of any protein of interest, as we show here for human p53 and E1A from human adenovirus 5. PMID- 24225581 TI - Improvement of the cloud point extraction of uranyl ions by the addition of ionic liquids. AB - The cloud point extraction (CPE) of uranyl ions by different kinds of extractants in Triton X-114 (TX-114) micellar solution was investigated upon the addition of ionic liquids (ILs) with various anions, i.e., bromide (Br(-)), tetrafluoroborate (BF4(-)), hexafluorophosphate (PF6(-)) and bis[(trifluoromethyl)sulfonyl]imide (NTf2(-)). A significant increase of the extraction efficiency was found on the addition of NTf2(-) based ILs when using neutral extractant tri-octylphosphine oxide (TOPO), and the extraction efficiency kept high at both nearly neutral and high acidity. However, the CPE with acidic extractants, e.g., bis(2-ethylhexyl) phosphoric acid (HDEHP) and 8-hydroxyquinoline (8-HQ) which are only effective at nearly neutral condition, was not improved by ILs. The results of zeta potential and (19)F NMR measurements indicated that the anion NTf2(-) penetrated into the TX-114 micelles and was enriched in the surfactant-rich phase during the CPE process. Meanwhile, NTf2(-) may act as a counterion in the CPE of UO2(2+) by TOPO. Furthermore, the addition of IL increased the separation factor of UO2(2+) and La(3+), which implied that in the micelle TOPO, NTf2(-) and NO3(-) established a soft template for UO2(2+). Therefore, the combination of CPE and IL provided a supramolecular recognition to concentrate UO2(2+) efficiently and selectively. PMID- 24225583 TI - Cationic polymer-immobilized polysulfone-based fibers as high performance sorbents for Pt(IV) recovery from acidic solutions. AB - This work reports a novel concept for the development of a polysulfone (PS)-based fiber as a high-performance acid-tolerant adsorbent for the recovery of platinum group metals (PGMs), particularly Pt(IV), in acidic media. Polyethylenimine (PEI) coated PS-Escherichia coli biomass composite fiber (PEI-PSBF) was prepared by spinning biomass-PS blends in water, coating with PEI and cross-linking with glutaraldehyde. The E. coli biomass on the fiber was executed as a functional group donor for binding PEI. PS fiber (PSF), PS-biomass composite fiber (PSBF), and PEI-modified PSF (PEI-PSF) were also prepared and compared with PEI-PSBF. The results of SEM and FTIR analyses revealed the presence of PEI on the surface of PEI-PSBF. Kinetic and isotherm experiments showed the negligible sorption capacity of PSF. In contrast, adsorption equilibrium on PSBF and PEI-PSBF was attained after 40 min and 6h, respectively. The maximum Pt(IV) uptake of PEI-PSBF was 6.6 times higher than that of PSBF. Pt(IV) ions were completely recovered from loaded PEI-PSBF by 0.1M thiourea in 1M HCl solution. The PEI-PSBF was also stable in 0.1M and 1M HCl solutions. The PEI-PSBF exhibited promising properties as an adsorbent for PGMs-containing acidic wastewaters. PMID- 24225582 TI - Physiological and proteomic changes suggest an important role of cell walls in the high tolerance to metals of Elodea nuttallii. AB - Macrophytes bioaccumulate metals, the suggestion being made that they be considered for phytoremediation. However, a thorough understanding of the mechanisms of metal tolerance in these plants is necessary to allow full optimization of this approach. The present study was undertaken to gain insight into Hg and Cd accumulation and their effects in a representative macrophyte, Elodea nuttallii. Exposure to methyl-Hg (23 ng dm(-3)) had no significant effect while inorganic Hg (70 ng dm(-3)) and Cd (281 MUg dm(-3)) affected root growth but did not affect shoots growth, photosynthesis, or antioxidant enzymes. Phytochelatins were confirmed as having a role in Cd tolerance in this plant while Hg tolerance seems to rely on different mechanisms. Histology and subcellular distribution revealed a localized increase in lignification, and an increased proportion of metal accumulation in cell wall over time. Proteomics further suggested that E. nuttallii was able to efficiently adapt its energy sources and the structure of its cells during Hg and Cd exposure. Storage in cell walls to protect cellular machinery is certainly predominant at environmental concentrations of metals in this plant resulting in a high tolerance highlighted by the absence of toxicity symptoms in shoots despite the significant accumulation of metals. PMID- 24225584 TI - Physics-based agent to simulant correlations for vapor phase mass transport. AB - Chemical warfare agent simulants are often used as an agent surrogate to perform environmental testing, mitigating exposure hazards. This work specifically addresses the assessment of downwind agent vapor concentration resulting from an evaporating simulant droplet. A previously developed methodology was used to estimate the mass diffusivities of the chemical warfare agent simulants methyl salicylate, 2-chloroethyl ethyl sulfide, di-ethyl malonate, and chloroethyl phenyl sulfide. Along with the diffusivity of the chemical warfare agent bis(2 chloroethyl) sulfide, the simulant diffusivities were used in an advection diffusion model to predict the vapor concentrations downwind from an evaporating droplet of each chemical at various wind velocities and temperatures. The results demonstrate that the simulant-to-agent concentration ratio and the corresponding vapor pressure ratio are equivalent under certain conditions. Specifically, the relationship is valid within ranges of measurement locations relative to the evaporating droplet and observation times. The valid ranges depend on the relative transport properties of the agent and simulant, and whether vapor transport is diffusion or advection dominant. PMID- 24225585 TI - Influence of generated intermediates' interaction on heterogeneous Fenton's degradation of an azo dye 1-diazo-2-naphthol-4-sulfonic acid by using sludge based carbon as catalyst. AB - Sewage sludge based carbons have recently been used as novel catalyst in heterogeneous Fenton's reactions to degrade azo dye molecules. The carbons, functioning as both catalyst and adsorbent, play an important role in pollutants elimination, especially for those simultaneously generated organic intermediates. Different factors, i.e., H2O2 concentration, may influence the type and properties of those intermediates and may have great impacts on their elimination through the interactions with catalysts' surface. Thus, techniques including Temperature Programmed Desorption-Mass Spectrometer (TPD-MS), N2 adsorption isotherm and Scanning Electron Microscope (SEM) were used to probe the ways of the interaction between oxidation products and catalyst by using different initial H2O2 concentrations (10 and 20mM). The higher Chemical Oxygen Demand (COD) removal with 20mM H2O2 was found to be related not only to the higher hydroxyl radicals but also the specific interactions between the intermediates and catalyst' surface. The deep oxidation occurred in the conditions with higher oxidant amount enhances the intermediates' adsorption on catalyst, thus increasing the COD removal by large margin. Simulated adsorption experiments by using six primarily formed intermediates and three deeply mineralized products on three different catalysts also confirmed the assumption. Results suggested close relations between adsorption capacities and intermediates' properties such as polar surface area and octanol-water partition coefficient. PMID- 24225586 TI - Transformation of 2,2',4,4'-tetrabromodiphenyl ether under UV irradiation: potential sources of the secondary pollutants. AB - A commercial brominated flame retardant 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) was used as the model chemical to investigate the degradation and transformation of polybrominated diphenyl ethers (PBDEs) in gas and liquid phases, respectively, under ultraviolet (UV) irradiation. The results showed that BDE-47 can be transformed to less-brominated BDE analogs. A total of six compounds that are less-brominated BDEs and two brominated phenols were observed as transformation products in the reaction mixtures. Different degradation rates of BDE-47 in n-nonane and in isooctane in the same chamber system were observed. Degradation rate of BDE-47 in n-nonane was faster than in isooctane. Under UV irradiation, the bromine on the ortho positions of the phenyl rings was lost first to form 2,4,4'-tribromodiphenyl ether (BDE-28), which then progressively lead to 4,4'-dibromodiphenyl ether (BDE-15) or 2,4'-dibromodiphenyl ether (BDE 8). An airborne transformation pathway has been proposed according to observed transformation products. The more volatile less-brominated BDEs from transformation of BDE-47 are easily evaporated into air to be a source of secondary pollutants in the environment. PMID- 24225587 TI - Reductive transformation of p-nitrophenol by Fe(II) species: the effect of anionic media. AB - Electron exchange between aqueous Fe(II) and structural Fe(III) of iron minerals has been illustrated for understanding the reduction of nitroaromatic compounds (NAC). However, factors influencing Fe(II)-induced the reduction of NAC still remain elusive. In this paper, p-nitrophenol (1.5mM) was selected to explore the effects of pH, the stabilizing ligands (Cl(-), SO4(2-)) of ferrous ions and the extra addition of iron hydroxide on the reduction of NAC via Fe(II) species. The results indicate that the reduction degree of is much lower in SO4(2-) medium than that in Cl(-) medium at pH 7.6. p-Nitrophenol reduction increased in SO4(2-) medium and slightly decreased in Cl(-) medium when Fe hydroxide was extra added. Cl(-) strength (0.01-0.1 mol L(-1)) has no obvious effect on p-NP reduction. SO4(2-) species and its dosage have markedly inhibitory effect on p-NP reduction due to the selective adsorption of SO4(2-) and the formation of sulphated surface complexes on the fresh Fe hydroxide. PMID- 24225588 TI - Isolation and characterization of a novel phenanthrene (PHE) degrading strain Psuedomonas sp. USTB-RU from petroleum contaminated soil. AB - The phenanthrene degrading novel bacterium strain USTB-RU was isolated from petroleum contaminated soil in Dagan oilfield, southeast of Tianjin, northeast China. The novel isolate was identified as Pseudomonas sp. USTB-RU on the basis of morphological, physicochemical characteristics and analysis of 16S rDNA gene sequence. The strain could degrade 86.65% of phenanthrene at an initial concentration of 100 mg L(-1) in 8 days and identified intermediate metabolite evident the biodegradation of phenanthrene through protocatechuate metabolic pathway. The strain showed the potential to produce surface-active compounds that may have caused for the resulted efficient biodegradation through enhancing the substrate bioavailability. The results highlighted that the adaptability of USTB RU to grow in a range of temperature, pH and potential to utilize various commonly co-exist pollutants in contaminated site other than phenanthrene as sole carbon and energy source. Further, susceptibility of the strain for the tested antibiotics inferred the possibility to absence of risk of spreading drug resistant factor to other indigenous bacteria. Therefore, the isolated novel strain USTB-RU may have a high potential for application in in situ bioremediation of phenanthrene contaminated environment. PMID- 24225589 TI - Fluorescent BINOL-based sensor for thorium recognition and a density functional theory investigation. AB - A novel 1,1'-bi-2-naphthol (BINOL) derivative fluorescence sensor L-1 for the recognition of thorium ion with a fluorescence quench response. This ligand showed high selectivity and sensitivity for thorium ion recognition. Coordination effects were investigated by DFT calculations, and the coordination modes and sites were confirmed. Moreover, the coordination abilities of the L-1 ligand with Th(4+) and UO2(2+) were evaluated. PMID- 24225590 TI - Exogenous auxin alleviates cadmium toxicity in Arabidopsis thaliana by stimulating synthesis of hemicellulose 1 and increasing the cadmium fixation capacity of root cell walls. AB - Auxin is involved in not only plant physiological and developmental processes but also plant responses to abiotic stresses. In this study, cadmium (Cd(2+)) stress decreased the endogenous auxin level, whereas exogenous auxin (alpha naphthaleneacetic acid, NAA, a permeable auxin analog) reduced shoot Cd(2+) concentration and rescued Cd(2+)-induced chlorosis in Arabidopsis thaliana. Under Cd(2+) stress conditions, NAA increased Cd(2+) retention in the roots and most Cd(2+) in the roots was fixed in hemicellulose 1 of the cell wall. NAA treatment did not affect pectin content and its binding capacity for Cd(2+), whereas it significantly increased the content of hemicellulose 1 and the amount of Cd(2+) retained in it. There were highly significant correlations between Cd(2+) concentrations in the root, cell wall and hemicellulose 1 when the plants were subjected to Cd(2+) or NAA+Cd(2+) treatment for 1 to 7d, suggesting that the increase in hemicellulose 1 contributes greatly to the fixation of Cd(2+) in the cell wall. Taken together, these results demonstrate that auxin-induced alleviation of Cd(2+) toxicity in Arabidopsis is mediated through increasing hemicellulose 1 content and Cd(2+) fixation in the root, thus reducing the translocation of Cd(2+) from roots to shoots. PMID- 24225591 TI - Influence of promoter on the catalytic activity of high performance Pd/PATP catalysts. AB - A series of Pd-M/PATP (M=Fe, Cu, Ce) catalysts applied in low temperature CO oxidation were prepared by a deposition-precipitation (DP) method. The techniques of N2 adsorption/desorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), temperature programmed reduction by H2 (H2-TPR), BET and ICP were employed for catalyst characterization. It was found that the Pd-Fe/PATP catalyst had superior activity than Pd-Cu/PATP and Pd-Ce/PATP catalyst under similar condition. The characterization results showed Pd nanoparticles of Pd-Fe/PATP catalyst were dispersed highly and small size. The effects of Fe loading content, calcination temperature and H2 reduction on low temperature CO catalytic oxidation were also investigated in detail. At 10 wt.% Fe loading, the catalyst which was calcined at 200 degrees C and no reduced with H2 had the highest activity. An additional reduction peak which was indicated by H2-TPR in the range of 200-250 degrees C (beside Pd oxide and Fe2O3) was detected in Pd-Fe-PATP catalyst when Fe content was 10 wt.%. It was ascribed to the reduction of weakly chemical-adsorbed oxygen and was very important to enhance the activity of Pd-Fe/PATP catalysts. From the analysis of research result, it could be seen that reaction pathway for low temperature CO oxidation over Pd-Fe/ATP was due to the Langmuir-Hinshelwood reaction mechanism. PMID- 24225592 TI - Quantitative dielectrophoretic tracking for characterization and separation of persistent subpopulations of Cryptosporidium parvum. AB - Microbial persistence to antibiotics is attributed to subpopulations with phenotypic variations that cause a spread of susceptibility levels, leading to the recurrence of infections and stability of biofilms. Herein, persistent oocyst subpopulations identified by animal infectivity and excystation assays during the disinfection of Cryptosporidium parvum, a water-borne pathogen capable of causing enteric infections at ultra-low doses, are separated and characterized by quantitative dielectrophoretic tracking over a wide frequency range (10 kHz-10 MHz). To enable the simultaneous and facile dielectrophoretic tracking of individual oocysts, insulator constrictions in a microfluidic channel are utilized to spatially modulate the localized field over the extent needed for defining oocyst trajectories and for obtaining high-resolution displacement versus time measurements under both, positive and negative dielectrophoresis. In this manner, by obviating the need for averaging dielectrophoretic data over a large collection region, the force response is more sensitive to differences in electrophysiology from sub-population fractions. Hence, the electrophysiology of sensitive and persistent oocysts after heat and silver nanoparticle treatments can be quantified by correlating the force response at low frequencies (<100 kHz) to the integrity of the oocyst wall and at high frequencies (0.4-1 MHz) to the sporozoites in the oocyst. This label-free method can characterize heterogeneous microbial samples with subpopulations of phenotypically different alterations, for quantifying the intensity of alteration and fraction with a particular alteration type. PMID- 24225593 TI - The selective transfer of patterned graphene. AB - We demonstrate a selective microcleaving graphene (MG) transfer technique for the transfer of graphene patterns and graphene devices onto chosen targets using a bilayer-polymer structure and femtosecond laser microfabrication. In the bilayer polymer structure, the first layer is used to separate the target graphene from the other flakes, and the second layer transfers the patterned graphene to the chosen targets. This selective transfer technique, which exactly transfers the patterned graphene onto a chosen target, leaving the other flakes on the original substrate, provides an efficient route for the fabrication of MG for microdevices and flexible electronics and the optimization of graphene's performance. This method will facilitate the preparation of van der Waals heterostructures and enable the optimization of the performance of graphene hybrid devices. PMID- 24225594 TI - Amphiphilic modification and asymmetric silica encapsulation of hydrophobic Au Fe3O4 dumbbell nanoparticles. AB - A facile method is developed for amphiphilic surface modification and asymmetric silica encapsulation of hydrophobic Au-Fe3O4 dumbbell nanoparticles. The obtained asymmetric Janus nanocomposites display tunable wettability, enhanced catalysis and better cell internalization as compared to those with complete silica encapsulation. PMID- 24225596 TI - When I grow up, I want to be a doctor, policeman, doctor...? PMID- 24225595 TI - Dose response of whey protein isolate in addition to a typical mixed meal on blood amino acids and hormonal concentrations. AB - The purpose was to investigate the effects of a controlled typical 1-day diet supplemented with two different doses of whey protein isolate on blood amino acid profiles and hormonal concentrations following the final meal. Nine males (age: 29.6 +/- 6.3 yrs) completed four conditions in random order: a control (C) condition of a typical mixed diet containing ~10% protein (0.8 g.kg1), 65% carbohydrate, and 25% fat; a placebo (P) condition calorically matched with carbohydrate to the whey protein conditions; a low-dose condition of 0.8 grams of whey protein isolate per kilogram body mass per day (g.kg1.d1; W1) in addition to the typical mixed diet; or a high-dose condition of 1.6 g.kg1.d1 (W2) of supplemental whey protein in addition to the typical mixed diet. Following the final meal, significant (p < .05) increases in total amino acids, essential amino acids (EAA), branch-chained amino acids (BCAA), and leucine were observed in plasma with whey protein supplementation while no changes were observed in the control and placebo conditions. There was no significant group difference for glucose, insulin, testosterone, cortisol, or growth hormone. In conclusion, supplementing a typical daily food intake consisting of 0.8 g of protein.kg1.d1 with a whey protein isolate (an additional 0.8 or 1.6 g.kg1.d1) significantly elevated total amino acids, EAA, BCAA, and leucine but had no effect on glucose, insulin, testosterone, cortisol, or growth hormone following the final meal. Future acute and chronic supplementation research examining the physiological and health outcomes associated with elevated amino acid profiles is warranted. PMID- 24225597 TI - NPWT or HRT-dressing? Results of an expert panel and a Delphi panel analysis. AB - OBJECTIVE: To investigate the similarities and differences between Hydration Response Technology (HRT) and negative pressure wound therapy (NPWT) with regard to wound bed preparation, and to devise a set of recommendations for their use on the basis of the opinion of two panels. METHOD: An expert panel that analysed in vitro and clinical data as well as the similarities and differences between the two modalities was established. This culminated in a series of recommendations on which modality to use for which indication. These recommendations were presented to a Delphi panel, consisting of users of both NPWT and HRT-dressing. The panel was then asked to produce its own recommendations. RESULTS: The outcomes and recommendations of both panels were reported. NPWT is the preferred treatment modality for abdominal dehisced wounds, and to a lesser extent, for surgical wound healing by secondary intention. For all other indications, the treatment modalities are at least equal, with HRT-dressing often being the superior mode to treat wounds such as venous leg ulcers, arterial ulcers and vasculitis. CONCLUSION: In the opinion of the expert panel and the Delphi panel, both modalities share a number of clinical and non-clinical properties. However, because of the numerous advantages of HRT technology, HRT dressing has the potential to replace NPWT in a number of indications, where the patient, health care providers and institutions may benefit. DECLARATION OF INTEREST: This study was sponsored by Sorbion GmbH & Co, Senden, Germany. Authors M. Hermans and K. Cutting are consultants to Sorbion GmbH & Co, Senden, Germany. PMID- 24225598 TI - Negative pressure wound therapy: improving the patient experience Part 2 of 3. AB - Despite the clear benefits of negative pressure wound therapy (NPWT) as a treatment for wounds, it is essential that greater focus is given to the patient experience of this treatment. In particular, it is important that any unpleasant consequences, such as pain, stress, and skin trauma are minimised, so as to promote quality of life and healing. This article presents part two of three studies which aim to explore ways in which the patient experience of NPWT can be improved. In this study, the views of wound care clinicians (n=12) were investigated in greater depth through semi-structured interviews. Findings indicate a pressing need to minimise pain, particularly through ongoing assessment and collaboration with patients, and also through the use of appropriate dressings, films and other products that promote patient comfort. Additionally, it is evident that greater education is needed for both nurses and patients about NPWT, in order to promote high-quality care and patient wellbeing. PMID- 24225599 TI - In vitro studies on the beneficial effect of a hydrokinetic fiber dressing on wound healing by reduction of protease activity. AB - OBJECTIVE: To test the binding capacity of a hydrokinetic fiber dressing for PMN elastase, MMP-2 and MMP-9 in vitro, and to determine whether testing of dressing material samples in vitro is sufficient to predict the performance of the whole dressing. METHOD: In vitro protease binding assays for PMN elastase, MMP-2 and MMP-9 were used to evaluate the protease modulating capacity of sorbion sachet EXTRA, a superabsorbant dressing that consists of special hydrokinetic fibers, which are formed from cellulose and sodium polyacrylate in a mechanical process without any bonding agents or adhesives. The ability of the hydrokinetic fiber dressing to inhibit elastase and collagenase activity was also tested at 0%, 50% and 100% saturation volume. RESULTS: The hydrokinetic fiber wound dressing was able to bind considerable amounts of elastase, reducing elastase activity by approximately 84%. Moreover, it significantly decreased MMP-2 and MMP-9 concentrations in vitro and was able to completely inhibit collagenase activity. CONCLUSION: In summary, the hydrokinetic fiber dressing sorbion sachet EXTRA was able to significantly reduce the concentration and activity of proteolytic enzymes in vitro. These results suggest that sorbion sachet EXTRA should have a beneficial action by reducing the detrimental effects of proteolytic enzymes in vivo. DECLARATION OF INTEREST: This work was supported by Sorbion GmbH & Co. KG, Senden, Germany. PMID- 24225600 TI - Report on a clinical evaluation of the KerraPro Heel silicone heel pad. AB - Heels are at increased risk of injury due to the posterior prominence and lack of padding over the calcaneus. Pressure injuries, once established, are extremely costly, both in terms of the detrimental effect on psychosocial wellbeing and threat to life, as well as financially due to length of hospital stay and resources used to heal the wounds. A new and inexpensive silicone heel pad has been designed to simplify the necessary decisions and to address the problems associated with pressure injuries to the heels. This article will describe an observational evaluation of the product. KerraPro Heel pads were evaluated in two separate cohorts of 17 participants over a 4-week period with the primary aim to evaluate the efficacy of the product in preventing and alleviating pressure injuries on the heels. All participants had been reported as 'at risk' or 'at high risk' of pressure injury to the heels and had a history of developing such lesions. The KerraPro heel pads were compared with the participant's standard protocol. The outcome of the evaluation demonstrated the effectiveness of the KerraPro Heel pads in the prevention and treatment of heel pressure injuries. PMID- 24225601 TI - Maximising the secondary beneficial effects of larval debridement therapy. AB - Laboratory-based clinical investigations have shown that maggots and their secretions promote, among other activities, fibroblast motogenesis and angiogenesis. These events would contribute to re-granulation if translated to the wound environment. Maggot secretions also have ascribed antibacterial actions and may exhibit anti-inflammatory effects. Many of these biological events would be lost in the presence of necrotic tissue, making debridement a prerequisite for the release of larval-secreted secondary beneficial effects on the wound. We argue that Larval Debridement Therapy (LDT) should be considered as a primary and secondary treatment in wound management, with the primary application designed to debride the wound, and with subsequent applications to the debrided wound targeted to cellular events that promote healing. This review lends support to a re-evaluation of larval application protocols, in order to optimally harness the potential secondary beneficial clinical effects of larval therapy. PMID- 24225602 TI - An exploration of fourth-year undergraduate nurses' knowledge of and attitude towards pressure ulcer prevention. AB - OBJECTIVE: To determine undergraduate nurses' knowledge of and attitudes towards pressure ulcer prevention. METHOD: A quantitative, cross-sectional survey design was used for this study. Ethical approval was received. A convenience sample of fourth-year undergraduate nurses was selected to participate (n=60). Data were collected using a pre-designed questionnaire. RESULTS: Overall, the participants showed a positive attitude towards pressure ulcer prevention but displayed poor knowledge of pressure ulcer prevention. Interestingly, having a high level of competency corresponded with having a positive attitude towards pressure ulcer prevention, but did not equate to possessing knowledge of pressure ulcer prevention. CONCLUSION: The findings of this study suggest that fourth-year undergraduates have a positive attitude but lack adequate knowledge on the prevention of pressure ulcers. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare. PMID- 24225603 TI - Feelings of powerlessness in patients with venous leg ulcers. AB - OBJECTIVE: To assess feelings of powerlessness in patients with venous leg ulcers. METHOD: An exploratory, descriptive, analytic, cross-sectional study was conducted at the Plastic Surgery Outpatient Clinic of the Sao Paulo Hospital (HSP) and at the Outpatient Wound-Care Clinic of the Sorocaba Hospital Complex (CHS), Brazil, from May 2010 to April 2012. Sixty patients with venous leg ulcers (VLUs), of both sexes, aged greater than or equal to 18 years, from the two outpatient wound-care clinics were selected to participate in the study. All participants responded to the Powerlessness Assessment Tool (PAT) for adult patients. Statistical analysis was performed using the Chi-square test, Mann Whitney U test and Kruskal-Wallis test at a significance level of 5% (p<0.05). RESULTS: Forty-four (73%) patients were women and 38 (63%) were aged 61-70 years. Eight (13%) patients were alcoholics and 46 (77%) were smokers. Thirty-two (53%) patients had a VLU for more than 10 years; the ulcer area ranged from 11-20 cm2 in 19 (32%) patients and was >30 cm2 in 18 (30%) patients. Mean total PAT score was 47.83 +/- 7.99 and ranged from 51-60 for 31 (52%) patients and from 41-50 for 19 (32%) patients. CONCLUSION: Most patients with venous leg ulcers reported high PAT scores, revealing the presence of strong feelings of powerlessness. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare. PMID- 24225604 TI - Hemisoleus muscle flap in the reconstruction of exposed bones in the lower limb. AB - OBJECTIVES: To evaluate the efficacy of soleus muscle flap for covering complex defects of the middle and lower leg. The study also outlines functional gain after the reconstructive procedure, the donor site morbidity and the technical details of the operative procedure. METHOD: This prospective study consists of a total of 40 patients with middle and lower third defects with exposed bone present in the leg. In all cases, a proximally-based hemisoleus flap was used. All patients were between 15-65 years of age. Depending upon the position of the defect and ease of rotation, either the medial or lateral hemisoleus was used to cover the defects. In 7 patients with large defects, both the hemi-gastrocnemius and hemisoleus flap were used. RESULTS: Most of the patients studied (52.5%) had defects in the middle third of their leg. A further 12(30%) patients had defects over the upper part of the lower third of the leg and 7(17.5%) cases involved large defects exposing bones comprising both the middle and lower thirds of the leg. All the flaps survived well except 5 which developed partial skin graft loss, and 1 where complete flap loss was observed. Out of 5 patients who developed partial graft loss, 3 patients achieved complete healing by regular dressings and 2 required regrafting. The patient who developed complete flap loss required below knee amputation. No donor site morbidity was observed, except minimal depression in the posterior leg. CONCLUSION: Due to a high degree of reliability, versatility, minimal donor site morbidity, less operating time, low cost and good functional gain, this procedure is highly suitable for the treatment of complex middle and lower leg defects. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare. PMID- 24225605 TI - 'Clinical and cost-effectiveness of absorbent dressings in the treatment of highly exuding VLUs'. PMID- 24225606 TI - Back to basics: histological, microbiological and biochemical sampling in wound care. AB - Despite the advances in our understanding of normal and abnormal wound healing over the past decade, a specific biomarker which can be used clinically to identify 'hard-to-heal' wounds still remains elusive. Tissue and exudate samples extracted from the site of the wound are traditionally analysed using histological, microbiological and biochemical laboratory techniques. The aim of this paper is to review the advantages of these techniques, their limitations and the rapid developments in the fields of microbiology and proteomics, which are offering new insights into the differences between healing and non-healing wounds. PMID- 24225607 TI - Developing a new, national approach to surveillance for ventilator-associated events: executive summary. PMID- 24225608 TI - Pediatric antimicrobial susceptibility trends across the United States. AB - OBJECTIVE: Antimicrobial susceptibility patterns across US pediatric healthcare institutions are unknown. A national pooled pediatric antibiogram (1) identifies nationwide trends in antimicrobial resistance, (2) allows across-hospital benchmarking, and (3) provides guidance for empirical antimicrobial regimens for institutions unable to generate pediatric antibiograms. METHODS: In January 2012, a request for submission of pediatric antibiograms between 2005 and 2011 was sent to 233 US hospitals. A summary antibiogram was compiled from participating institutions to generate proportions of antimicrobial susceptibility. Temporal and regional comparisons were evaluated using chi(2) tests and logistic regression, respectively. RESULTS: Of 200 institutions (85%) responding to our survey, 78 (39%) reported generating pediatric antibiograms, and 55 (71%) submitted antibiograms. Carbapenems had the highest activity against the majority of gram-negative organisms tested, but no antibiotic had more than 90% activity against Pseudomonas aeruginosa. Approximately 50% of all Staphylococcus aureus isolates were methicillin resistant. Western hospitals had significantly lower proportions of S. aureus that were methicillin resistant compared with all other regions tested. Overall, 21% of S. aureus isolates had resistance to clindamycin. Among Enterococcus faecium isolates, the prevalence of susceptibility to ampicillin (25%) and vancomycin (45%) was low but improved over time (P< .01), and 8% of E. faecium isolates were resistant to linezolid. Southern hospitals reported significantly higher prevalence of E. faecium with susceptibilities to ampicillin, vancomycin, and linezolid compared with the other 3 regions (P< .01). CONCLUSIONS: A pooled, pediatric antibiogram can identify nationwide antimicrobial resistance patterns for common pathogens and might serve as a useful tool for benchmarking resistance and informing national prescribing guidelines for children. PMID- 24225609 TI - Identifying targets for antimicrobial stewardship in children's hospitals. AB - OBJECTIVE: Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts. DESIGN: Retrospective cross-sectional study. SETTING AND PATIENTS: Children admitted to 32 freestanding children's hospitals in the United States in 2010. METHODS: We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient days, adjusting for patient demographics and severity of illness. RESULTS: In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions. CONCLUSIONS: Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions. PMID- 24225610 TI - The use of best practice alerts with the development of an antimicrobial stewardship navigator to promote antibiotic de-escalation in the electronic medical record. AB - OBJECTIVE: Develop a clinical decision support tool comprised of an electronic medical record alert and antimicrobial stewardship navigator to facilitate antimicrobial stewardship. DESIGN: We analyzed alerts targeting antimicrobial de escalation to assess the effectiveness of the navigator as a stewardship tool. The alert provides antimicrobial recommendations, then directs providers to the navigator, which includes order management, relevant patient information, evidence-based clinical information, and bidirectional communication capability. SETTING: Academic, tertiary care medical center with an electronic medical record. INTERVENTION: Alerts containing stewardship recommendations and immediate access to the navigator were created. RESULTS: Antibiotic use and response data were collected 1 day before stewardship recommendation via the best practice alert (BPA) tool and 1 day after the BPA tool response. A total of 1,285 stewardship BPAs were created. Two hundred and forty-four (18.9%) of the BPAs were created and acted upon within 72 hours for the purpose of de-escalation: 169 (69%) were accepted, 30 (12%) were accepted with modification, and 45 (18%) were rejected. Statistically significant decreases in total antibiotic use as well as in use of broad-spectrum (anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal) agents occurred when accepted recommendations were compared with rejected recommendations. CONCLUSIONS: We describe the successful development of a clinical decision support tool to perform prospective audit and feedback comprised of an alert and navigator system featuring evidence-based recommendations and clinical and educational information. We demonstrate that this tool improves antibiotic use through our example of de-escalation. PMID- 24225611 TI - Incidence, classification, and risk stratification for Candida central line associated bloodstream infections in pediatric patients at a tertiary care children's hospital, 2000-2010. AB - OBJECTIVE: To identify risk factors for pediatric Candida central line-associated bloodstream infections (CLABSIs). DESIGN: Retrospective case-control study. SETTING: Freestanding tertiary care children's hospital. PATIENTS: Patients with Candida CLABSI from January 31, 2000, through December 31, 2010, compared with age- and year-matched controls. METHODS: Demographics, comorbidities, presence of indwelling foreign bodies, exposure to antibiotics or corticosteroids, total parenteral nutrition (TPN) or blood transfusions, complications, and outcome were evaluated. Bivariate and then logistic regression were used to compare temporal trends and risk factors. Results. A total of 160 Candida CLABSI patients (median age, 1.96 years) were compared with 457 controls. Those with Candida CLABSIs were more likely to have intestinal failure (adjusted odds ratio [aOR], 6.777 [95% confidence interval (CI), 2.315-19.839]; P< .001), to have a gastrostomy tube in place (aOR, 4.156 [95% CI, 2.317-7.456]; P< .001), and to receive TPN (aOR, 3.897 [95% CI, 2.403-6.319]; P< .001) or blood transfusions (aOR, 2.990 [95% CI, 1.841 4.856]; P< .001), and they had a 3-fold increase in mortality (aOR, 3.543 [95% CI, 1.501-8.364]; P< .004). Candida albicans was most common, but non-albicans strains resistant to amphotericin (C. lusitaniae) and fluconazole (C. glabrata and C. krusei) were also found. Conclusions. Those patients with intestinal failure, gastrostomy tube presence, and/or receipt of TPN and blood transfusions are at increased risk for development of Candida CLABSI. PMID- 24225612 TI - Management of neurosurgical instruments and patients exposed to Creutzfeldt-Jakob disease. AB - OBJECTIVE: To summarize the approaches used to manage exposure of patients to inadequately sterilized neurosurgical instruments contaminated as a result of Creutzfeldt-Jakob disease (CJD). METHODS: Information on past CJD exposure incidents reported to the Centers for Disease Control and Prevention (CDC) was aggregated and summarized. In addition, inactivation studies were reviewed, and data from selected publications were provided for reference. RESULTS: Nineteen incidents of patient exposure to potentially CJD-contaminated instruments were reported to the CDC, including 17 that involved intracranial procedures and 2 that involved ophthalmologic procedures. In more than 50% of incidents, the neurosurgical procedures were performed for diagnostic work up of the index patients. At least 12 of the hospitals had multiple neurosurgical sets, and the CJD-contaminated instruments could not be identified in 11 of 19 hospitals. In 12 of 15 hospitals with neurosurgical incidents, a decision was made to notify patients of their potential exposure. CONCLUSIONS: Neurosurgical instruments used for treatment of patients with suspected or diagnosed CJD or patients whose diagnosis is unclear should be promptly identified and sterilized using recommended CJD decontamination protocols. Inability to trace instruments complicates appropriate management of exposure incidents. The feasibility of instituting instrument tracking procedures should be considered. PMID- 24225613 TI - Incidence and pathogen distribution of healthcare-associated infections in pilot hospitals in Egypt. AB - OBJECTIVE: To report type and rates of healthcare-associated infections (HAIs) as well as pathogen distribution and antimicrobial resistance patterns from a pilot HAI surveillance system in Egypt. METHODS: Prospective surveillance was conducted from April 2011 through March 2012 in 46 intensive care units (ICUs) in Egypt. Definitions were adapted from the Centers for Disease Control and Prevention's National Healthcare Safety Network. Trained healthcare workers identified HAIs and recorded data on clinical symptoms and up to 4 pathogens. A convenience sample of clinical isolates was tested for antimicrobial resistance at a central reference laboratory. Multidrug resistance was defined by international consensus criteria. RESULTS: ICUs from 11 hospitals collected 90,515 patient-days of surveillance data. Of 472 HAIs identified, 47% were pneumonia, 22% were bloodstream infections, and 15% were urinary tract infections; case fatality among HAI case patients was 43%. The highest rate of device-associated infections was reported for ventilator-associated pneumonia (pooled mean rate, 7.47 cases per 1,000 ventilator-days). The most common pathogens reported were Acinetobacter species (21.8%) and Klebsiella species (18.4%). All Acinetobacter isolates tested (31/31) were multidrug resistant, and 71% (17/24) of Klebsiella pneumoniae isolates were extended-spectrum beta-lactamase producers. CONCLUSIONS: Infection control priorities in Egypt should include preventing pneumonia and preventing infections due to antimicrobial-resistant pathogens. PMID- 24225614 TI - Infection control knowledge, attitudes, and practices among healthcare workers in Addis Ababa, Ethiopia. AB - OBJECTIVE: To better understand hospital infection control practices in Ethiopia. DESIGN: A cross-sectional evaluation of healthcare worker (HCW) knowledge, attitudes, and practices about hand hygiene and tuberculosis (TB) infection control measures. METHODS: An anonymous 76-item questionnaire was administered to HCWs at 2 university hospitals in Addis Ababa, Ethiopia. Knowledge items were scored as correct/incorrect. Attitude and practice items were assessed using a Likert scale. RESULTS: In total, 261 surveys were completed by physicians (51%) and nurses (49%). Fifty-one percent of respondents were male; mean age was 30 years. While hand hygiene knowledge was fair, self-reported practice was suboptimal. Physicians reported performing hand hygiene 7% and 48% before and after patient contact, respectively. Barriers for performing hand hygiene included lack of hand hygiene agents (77%), sinks (30%), and proper training (50%) as well as irritation and dryness (67%) caused by hand sanitizer made in accordance with the World Health Organization formulation. TB infection control knowledge was excellent (more than 90% correct). Most HCWs felt that they were at high risk for occupational acquisition of TB (71%) and that proper TB infection control can prevent nosocomial transmission (92%). Only 12% of HCWs regularly wore a mask when caring for TB patients. Only 8% of HCWs reported that masks were regularly available, and 76% cited a lack of infrastructure to isolate suspected/known TB patients. CONCLUSIONS: Training HCWs about the importance and proper practice of hand hygiene along with improving hand sanitizer options may improve patient safety. Additionally, enhanced infrastructure is needed to improve TB infection control practices and allay HCW concerns about acquiring TB in the hospital. PMID- 24225615 TI - Innovative solution to sharp waste management in a tertiary care hospital in Karachi, Pakistan. AB - BACKGROUND: Prevalence of hepatitis B and C in Pakistan is 2.5% and 4.5%, respectively. Major cause of these infections is reuse of syringes. OBJECTIVE: To determine a cost-effective, innovative solution to prevent syringe reuse and break the transmission cycle of blood-borne infections. STUDY DESIGN, SETTINGS, AND DURATION: Analytical study in a tertiary care hospital, Jinnah Postgraduate Medical Centre, Karachi, Pakistan, July 2011 to June 2012. METHODS: Healthcare workers from 30 wards included in the study were trained on injection safety, use of needle remover and needle pit, and management of needlestick injuries. Each ward was provided with 2 needle-removing devices, and a pit was constructed for disposal of needles. Usage of the device in wards and pit use were monitored regularly. RESULTS: In 28 (93.3%) wards, sharp containers were accessible by public and were slack. Syringes were recapped using both hands in 27 (90%) cases; needlestick injury was reported by 30% of paramedics, while 25 (83.3%) of the interviewed staff had not received any formal training in injection safety. Vigilant monitoring and information sharing led to healthcare workers in 28 (96.5%) wards using the device. Needle containers were emptied in 27 (93.1%) wards, and needle pits were used in 26 (96.3%) wards. Needlestick injury was nil in follow-up. CONCLUSIONS: Needle removers permanently disable syringes. The needle pit served as a cost-effective, innovative method for disposal of needles. The intervention resulted in reducing the risk of needlestick injury. PMID- 24225616 TI - Assessment for possible healthcare-associated transmission of a new variant influenza virus--Pennsylvania, August 2011. AB - In August 2011, one of the earliest cases of influenza A(H3N2) variant [A(H3N2)v] virus infection was hospitalized with severe illness. To investigate the potential for healthcare-associated transmission of influenza A(H3N2)v, we evaluated both healthcare providers and patient contacts of the case. We found that healthcare-associated transmission was unlikely. PMID- 24225617 TI - Carbapenem de-escalation therapy in a resource-limited setting. AB - Pulmonary infection (P=.01) and an infectious diseases consultation (P=.04) were associated with carbapenem de-escalation; pulmonary infection and septic shock were associated with unsuccessful de-escalation. Successful de-escalation was associated with lower mortality (0% vs 23%; P<.001) and shorter duration of carbapenem use (4 vs 10 days; P <= .001). PMID- 24225618 TI - Impact of different catheter lock strategies on bacterial colonization of permanent central venous hemodialysis catheters. AB - Thirty-nine hemodialysis patients with permanent central venous catheters were analyzed for bacterial catheter colonization comparing different catheter-lock strategies. The closed needleless Tego connector with sodium chloride lock solution was significantly more frequently colonized with bacteria than the standard catheter caps with antimicrobially active citrate lock solution (odds ratio, 0.22 [95% confidence interval, 0.07-0.71]; P = .011). PMID- 24225619 TI - The impact of observation units on the rate of hospital-acquired infection. AB - Using Clostridium difficile as an example, we calculated the impact that reduced inpatient-day denominators resulting from implementation of hospital observation units would have on hospital-acquired infection rates. Using proposed scenarios of reduced inpatient-days, we estimated an increase in the hospital-acquired C. difficile infection rate of up to 12%. PMID- 24225620 TI - Harnessing claims to improve detection of surgical site infections following hysterectomy and colorectal surgery. AB - Surgical site infection (SSI) surveillance is performed using a variety of methods with unclear performance characteristics. We used claims data to identify records for review following hysterectomy and colorectal surgery. Claims-enhanced screening identified SSIs missed by routine surveillance and could be used for targeted chart review to improve SSI detection. PMID- 24225621 TI - A multicenter study measuring appropriateness of carbapenem use. PMID- 24225622 TI - Frequency of disinfectant resistance genes in pediatric strains of methicillin resistant Staphylococcus aureus. PMID- 24225623 TI - Development of a core team for the management of peripherally inserted central catheters. PMID- 24225624 TI - Reply to Parcell et al. PMID- 24225625 TI - Mucosal barrier injury laboratory--confirmed bloodstream infection or contaminant? PMID- 24225626 TI - Monitoring of cleaning practices for portable, multiuse medical equipment. PMID- 24225627 TI - Sharing eyedrops between patients: when will it end? PMID- 24225628 TI - Survival of a surrogate virus on N95 respirator material. PMID- 24225629 TI - Evaluation of universal methicillin-resistant Staphylococcus aureus screening using nasal polymerase chain reaction compared with nasal, axilla, and groin and throat and perianal cultures in a hospital setting. PMID- 24225630 TI - Multiple-locus variable number tandem repeat analysis typing of vancomycin resistant Enterococcus faecium in Serbia. PMID- 24225631 TI - Clostridium difficile 027 emerging outbreak in Marseille, France. PMID- 24225634 TI - Simultaneous quantification of cocaine, amphetamines, opiates and cannabinoids in vitreous humor. AB - A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was <10.4% for all the analytes and accuracy ranged from 95.6 to 104.0%. An limit of quantitation for all drugs was 10 ng/mL and recoveries ranged from 70.4 to 100.1% for basic and neutral compounds; the acid compounds had poor recovery--<40%. The validated method was applied to 10 VH samples taken from individuals whose blood had screened positive for drugs of abuse. All the individuals screened positive for COC in the blood (seven samples) also had positive results in VH; COC concentration ranged from 30.81 to 283.97 ng/mL (mean 186.98 ng/mL) and benzoylecgonine concentration ranged from 11.47 to 460.98 ng/mL (mean 133.91 ng/mL). It was also noticed that, in five cases, cocaethylene was detected. AEME was also quantified in one case. The use of AMP detected by blood analysis was confirmed in the VH of one individual (24.31 ng/mL). However, samples taken from three individuals whose blood tested positive for carboxy-tetrahydrocannabinol presented negative results. The results demonstrated that VH is a suitable alternative biological sample to determine COC, AMPs, opiates and their metabolites. PMID- 24225635 TI - Ni(II) tetraphosphine complexes as catalysts/initiators in the ring opening polymerization of epsilon-caprolactone. AB - Reactions of the tetraphosphine ligand N,N,N',N' tetra(diphenylphosphanylmethyl)ethylene diamine) (dppeda) or 1,4-N,N,N',N' tetra(diphenylphosphanylmethyl)benzene diamine (dpppda) with NiCl2, ancillary ligand (C2H5)2NCS2Na (Na(dtc)) and NH4PF6 afforded two binuclear complexes [(dtc)Ni(dppeda)Ni(dtc)](PF6)2 (1) and [(dtc)Ni(dpppda)Ni(dtc)](PF6)2 (2). Compounds 1 and 2 were characterized by elemental analyses, IR spectra, (1)H, (13)C{(1)H} NMR and (31)P{(1)H} NMR, electrospray ionization (ESI) mass spectra, thermogravimetric (TGA) experiments and single crystal X-ray diffraction. The Ni(ii) atoms in both compounds form a square planar coordination geometry while the ligands hold a similar end-to-end coordination mode. Both products can catalyze the ring-opening polymerization (ROP) of epsilon-caprolactone (epsilon CL) while 1 exhibited a higher catalytic activity than 2. Influencing aspects such as solvent, temperature, the ratio of epsilon-CL to catalyst, the presence of benzyl alcohol, concentration of epsilon-CL and reaction intervals were investigated. PMID- 24225636 TI - Boning up on autophagy: the role of autophagy in skeletal biology. AB - From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the heart and lungs (ribs) and spinal cord (vertebrae and intervertebral discs). However, bone has a considerable number of other functions: serving as a store for mineral ions, providing a site for blood cell synthesis and participating in a complex system-wide endocrine system. Not surprisingly, bone and cartilage cell homeostasis is tightly controlled, as is the maintenance of tissue structure and mass. While a great deal of new information is accruing concerning skeletal cell homeostasis, one relatively new observation is that the cells of bone (osteoclasts osteoblasts and osteocytes) and cartilage (chondrocytes) exhibit autophagy. The focus of this review is to examine the significance of this process in terms of the functional demands of the skeleton in health and during growth and to provide evidence that dysregulation of the autophagic response is involved in the pathogenesis of diseases of bone (Paget disease of bone) and cartilage (osteoarthritis and the mucopolysaccharidoses). Delineation of molecular changes in the autophagic process is uncovering new approaches for the treatment of diseases that affect the axial and appendicular skeleton. PMID- 24225638 TI - Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach. AB - Recombinant adeno-associated viruses are important vectors for retinal gene delivery. Currently utilized vectors have relatively slow onset, and for efficient transduction it is necessary to deliver treatment subretinally, with the potential for damage to the retina. Amino-acid substitutions in the viral capsid improve efficiency in rodent eyes by evading host responses. As dogs are important large animal models for human retinitis pigmentosa, we evaluated the speed and efficiency of retinal transduction using capsid-mutant vectors injected both subretinally and intravitreally. We evaluated AAV serotypes 2 and 8 with amino-acid substitutions of surface-exposed capsid tyrosine residues. The chicken beta-actin promoter was used to drive green fluorescent protein expression. Twelve normal adult beagles were injected; four dogs received intravitreal injections and eight dogs received subretinal injections. Capsid-mutant viruses tested included AAV2(quad Y-F) (intravitreal and subretinal) and self complementary scAAV8(Y733F) (subretinal only). Contralateral control eyes received injections of scAAV5 (subretinal) or scAAV2 (intravitreal). Subretinally delivered vectors had a faster expression onset than intravitreally delivered vectors. Subretinally delivered scAAV8(Y733F) had a faster onset of expression than scAAV5. All subretinally injected vector types transduced the outer retina with high efficiency and the inner retina with moderate efficiency. Intravitreally delivered AAV2(quad Y-F) had a marginally higher efficiency of transduction of both outer retinal and inner retinal cells than scAAV2. Because of their rapid expression onset and efficient transduction, subretinally delivered capsid-mutant AAV8 vectors may increase the efficacy of gene therapy treatment for rapid photoreceptor degenerative diseases. With further refinement, capsid-mutant AAV2 vectors show promise for retinal gene delivery from an intravitreal approach. PMID- 24225639 TI - Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. AB - For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies. PMID- 24225640 TI - Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice. AB - Mutations in GJB2, which codes for the gap junction (GJ) protein connexin26 (Cx26), are the most common causes of human nonsyndromic hereditary deafness. We inoculated modified adeno-associated viral (AAV) vectors into the scala media of early postnatal conditional Gjb2 knockout mice to drive exogenous Cx26 expression. We found extensive virally expressed Cx26 in cells lining the scala media, and intercellular GJ network was re-established in the organ of Corti of mutant mouse cochlea. Widespread ectopic Cx26 expression neither formed ectopic GJs nor affected normal hearing thresholds in wild-type (WT) mice, suggesting that autonomous cellular mechanisms regulate proper membrane trafficking of exogenously expressed Cx26 and govern the functional manifestation of them. Functional recovery of GJ-mediated coupling among the supporting cells was observed. We found that both cell death in the organ of Corti and degeneration of spiral ganglion neurons in the cochlea of mutant mice were substantially reduced, although auditory brainstem responses did not show significant hearing improvement. This is the first report demonstrating that virally mediated gene therapy restored extensive GJ intercellular network among cochlear non-sensory cells in vivo. Such a treatment performed at early postnatal stages resulted in a partial rescue of disease phenotypes in the cochlea of the mutant mice. PMID- 24225641 TI - Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies. AB - Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3(+) engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3(+), CD4(+), and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD. PMID- 24225642 TI - Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques. AB - Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-gamma, IL-2 and TNF-alpha) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge. PMID- 24225643 TI - Lithium in tap water and suicide mortality in Japan. AB - Lithium has been used as a mood-stabilizing drug in people with mood disorders. Previous studies have shown that natural levels of lithium in drinking water may protect against suicide. This study evaluated the association between lithium levels in tap water and the suicide standardized mortality ratio (SMR) in 40 municipalities of Aomori prefecture, which has the highest levels of suicide mortality rate in Japan. Lithium levels in the tap water supplies of each municipality were measured using inductively coupled plasma-mass spectrometry. After adjusting for confounders, a statistical trend toward significance was found for the relationship between lithium levels and the average SMR among females. These findings indicate that natural levels of lithium in drinking water might have a protective effect on the risk of suicide among females. Future research is warranted to confirm this association. PMID- 24225645 TI - How do grass species, season and ensiling influence mycotoxin content in forage? AB - Mycotoxins are secondary metabolites produced by fungal species that have harmful effects on mammals. The aim of this study was to assess the content of mycotoxins in fresh-cut material of selected forage grass species both during and at the end of the growing season. We further assessed mycotoxin content in subsequently produced first-cutting silages with respect to the species used in this study: Lolium perenne (cv. Kentaur), Festulolium pabulare (cv. Felina), Festulolium braunii (cv. Perseus), and mixtures of these species with Festuca rubra (cv. Gondolin) or Poa pratensis (Slezanka). The mycotoxins deoxynivalenol, zearalenone and T-2 toxin were mainly detected in the fresh-cut grass material, while fumonisin and aflatoxin contents were below the detection limits. July and October were the most risky periods for mycotoxins to occur. During the cold temperatures in November and December, the occurrence of mycotoxins in fresh-cut material declined. Although June was a period with low incidence of mycotoxins in green silage, contents of deoxynivalenol and zearalenone in silages from the first cutting exceeded by several times those determined in their biomass collected directly from the field. Moreover, we observed that use of preservatives or inoculants did not prevent mycotoxin production. PMID- 24225646 TI - Impediments to comprehensive research on climate change and health. AB - During every climatic era Life on Earth is constrained by a limited range of climatic conditions, outside which thriving and then surviving becomes difficult. This applies at both planetary and organism (species) levels. Further, many causal influences of climate change on human health entail changes-often disruptive, sometimes irreversible-in complex system functioning. Understanding the diverse health risks from climate change, and their influence pathways, presents a challenge to environmental health researchers whose prior work has been in a more definable, specific and quantitative milieu. Extension of the research agenda and conceptual framework to assess present and future health risks from climate change may be constrained by three factors: (i) lack of historically-informed understanding of population-health sensitivity to climatic changes; (ii) an instinctual 'epidemiologising' tendency to choose research topics amenable to conventional epidemiological analysis and risk estimation; and (iii) under-confidence in relation to interdisciplinary collaborative scenario based modeling of future health risks. These constraints must be recognized and remedied. And environmental researchers must argue for heightened public attention to today's macro-environmental threats to present and future population health-emphasising the ecological dimension of these determinants of long-term health that apply to whole populations and communities, not just to individuals and social groupings. PMID- 24225647 TI - IAServ: an intelligent home care web services platform in a cloud for aging-in place. AB - As the elderly population has been rapidly expanding and the core tax-paying population has been shrinking, the need for adequate elderly health and housing services continues to grow while the resources to provide such services are becoming increasingly scarce. Thus, increasing the efficiency of the delivery of healthcare services through the use of modern technology is a pressing issue. The seamless integration of such enabling technologies as ontology, intelligent agents, web services, and cloud computing is transforming healthcare from hospital-based treatments to home-based self-care and preventive care. A ubiquitous healthcare platform based on this technological integration, which synergizes service providers with patients' needs to be developed to provide personalized healthcare services at the right time, in the right place, and the right manner. This paper presents the development and overall architecture of IAServ (the Intelligent Aging-in-place Home care Web Services Platform) to provide personalized healthcare service ubiquitously in a cloud computing setting to support the most desirable and cost-efficient method of care for the aged aging in place. The IAServ is expected to offer intelligent, pervasive, accurate and contextually-aware personal care services. Architecturally the implemented IAServ leverages web services and cloud computing to provide economic, scalable, and robust healthcare services over the Internet. PMID- 24225644 TI - Flaviviruses in Europe: complex circulation patterns and their consequences for the diagnosis and control of West Nile disease. AB - In Europe, many flaviviruses are endemic (West Nile, Usutu, tick-borne encephalitis viruses) or occasionally imported (dengue, yellow fever viruses). Due to the temporal and geographical co-circulation of flaviviruses in Europe, flavivirus differentiation by diagnostic tests is crucial in the adaptation of surveillance and control efforts. Serological diagnosis of flavivirus infections is complicated by the antigenic similarities among the Flavivirus genus. Indeed, most flavivirus antibodies are directed against the highly immunogenic envelope protein, which contains both flavivirus cross-reactive and virus-specific epitopes. Serological assay results should thus be interpreted with care and confirmed by comparative neutralization tests using a panel of viruses known to circulate in Europe. However, antibody cross-reactivity could be advantageous in efforts to control emerging flaviviruses because it ensures partial cross protection. In contrast, it might also facilitate subsequent diseases, through a phenomenon called antibody-dependent enhancement mainly described for dengue virus infections. Here, we review the serological methods commonly used in WNV diagnosis and surveillance in Europe. By examining past and current epidemiological situations in different European countries, we present the challenges involved in interpreting flavivirus serological tests and setting up appropriate surveillance programs; we also address the consequences of flavivirus circulation and vaccination for host immunity. PMID- 24225648 TI - Evaluating multipollutant exposure and urban air quality: pollutant interrelationships, neighborhood variability, and nitrogen dioxide as a proxy pollutant. AB - BACKGROUND: Although urban air pollution is a complex mix containing multiple constituents, studies of the health effects of long-term exposure often focus on a single pollutant as a proxy for the entire mixture. A better understanding of the component pollutant concentrations and interrelationships would be useful in epidemiological studies that exploit spatial differences in exposure by clarifying the extent to which measures of individual pollutants, particularly nitrogen dioxide (NO2), represent spatial patterns in the multipollutant mixture. OBJECTIVES: We examined air pollutant concentrations and interrelationships at the intraurban scale to obtain insight into the nature of the urban mixture of air pollutants. METHODS: Mobile measurements of 23 air pollutants were taken systematically at high resolution in Montreal, Quebec, Canada, over 34 days in the winter, summer, and autumn of 2009. RESULTS: We observed variability in pollution levels and in the statistical correlations between different pollutants according to season and neighborhood. Nitrogen oxide species (nitric oxide, NO2, nitrogen oxides, and total oxidized nitrogen species) had the highest overall spatial correlations with the suite of pollutants measured. Ultrafine particles and hydrocarbon-like organic aerosol concentration, a derived measure used as a specific indicator of traffic particles, also had very high correlations. CONCLUSIONS: Our findings indicate that the multipollutant mix varies considerably throughout the city, both in time and in space, and thus, no single pollutant would be a perfect proxy measure for the entire mix under all circumstances. However, based on overall average spatial correlations with the suite of pollutants measured, nitrogen oxide species appeared to be the best available indicators of spatial variation in exposure to the outdoor urban air pollutant mixture. PMID- 24225649 TI - Autophagy during beef aging. AB - The conversion of muscle into meat is a complex process of major concern for meat scientists due to its influence on the final meat quality. The aim of this study was to investigate the occurrence of autophagic processes in the conversion of muscle into meat. Our findings demonstrated, for the first time, the occurrence of autophagic processes in the muscle tissue at early postmortem period (2 h to 24 h) in both beef breeds studied (Asturiana de los Valles and Asturiana de la Montana) showing significant time-scale differences between breeds, which could indicate a role of this process in meat maturation. These breeds have different physiological features: while Asturiana de los Valles is a meat-specialized breed showing high growth rate, an elevated proportion of white fibers in the muscle and low intramuscular fat level, Asturiana de la Montana is a small- to medium sized rustic breed adapted to less-favored areas, showing more red fibers in the muscle and a high intramuscular fat content. PMID- 24225650 TI - Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field. AB - Biological clocks have evolved as an adaptation to life on a rhythmic planet, synchronising physiological processes to the environmental light-dark cycle. Here we examine circadian clock function in Mexican blind cavefish Astyanax mexicanus and its surface counterpart. In the lab, adult surface fish show robust circadian rhythms in per1, which are retained in cave populations, but with substantial alterations. These changes may be due to increased levels of light-inducible genes in cavefish, including clock repressor per2. From a molecular standpoint, cavefish appear as if they experience 'constant light' rather than perpetual darkness. Micos River samples show similar per1 oscillations to those in the lab. However, data from Chica Cave shows complete repression of clock function, while expression of several light-responsive genes is raised, including DNA repair genes. We propose that altered expression of light-inducible genes provides a selective advantage to cavefish at the expense of a damped circadian oscillator. PMID- 24225651 TI - Effects of site-specific level adjustments on speech recognition with cochlear implants. AB - OBJECTIVES: Modulation detection thresholds (MDTs) vary across stimulation sites in a cochlear implant (CI) electrode array in a manner that is subject and ear specific. Previous studies have demonstrated that speech recognition with a CI can be improved by site-selection strategies, where selected stimulation sites with poor modulation sensitivity are removed from a subject's processor MAP. Limitations of site-selection strategies are that they can compromise spectral resolution and distort frequency-place mapping because the frequencies assigned to the removed sites are usually reallocated to other sites, and site bandwidths are broadened. The objective of the present study was to test an alternative approach for rehabilitation that aimed at improving the across-site mean MDTs by adjusting stimulation parameters at the poorly performing sites. On the basis of previous findings that modulation detection contributes to speech recognition and improves significantly with stimulus level, the authors hypothesized that modulation sensitivity at the poor sites could be improved by artificially increasing stimulation levels at those sites in the speech processor, which then would lead to improved speech recognition. DESIGN: Nine postlingually deafened ears implanted with Nucleus CIs were evaluated for MDTs, absolute-detection threshold levels (T levels), and the maximum loudness levels (C levels) on each of the available stimulation sites. For each ear, the minimum stimulation level settings in the speech-processor MAP were raised by 5%, and alternatively by 10%, of the dynamic range (DR) from true thresholds on five stimulation sites with the poorest MDTs. For comparison, a 5% level raise was applied globally to all stimulation sites. The C levels were fixed during these level manipulations. MDTs at the five poorest stimulation sites were compared at 20% DR before and after the level adjustments. Speech-reception thresholds (SRTs), that is, signal to noise ratios required for 50% correct speech recognition, were evaluated for these MAPs using CUNY sentences. The site-specific level-adjusted MAPs were compared with the global-level-adjusted MAP and the MAP without level adjustment. The effects on speech recognition of adjusting the minimal stimulation level settings on the five poorest stimulation sites were also compared with effects of removing these sites from the speech-processor MAP. RESULTS: The 5% level increase on the five electrodes with the worst MDTs resulted in an improvement in the group mean SRT of 2.36 dB SNR relative to the MAP without level adjustment. The magnitude of level increase that resulted in the greatest SRT improvement for individuals varied across ears. MDTs measured at 20% DR significantly improved on the poor sites after the level adjustment that resulted in the best SRT for that ear was applied. Increasing the minimal stimulation levels on all stimulation sites or removing sites selected for rehabilitation, the parsimonious approaches, did not improve SRTs. CONCLUSIONS: The site-specific adjustments of the T level settings improved modulation sensitivity at low levels and significantly improved subjects' SRTs. Thus, this site-rehabilitation strategy was an effective alternative to site-selection strategies for improving speech recognition in CI users. PMID- 24225652 TI - Auditory phenotype of Niemann-Pick disease, type C1. AB - OBJECTIVES: The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-beta-cyclodextrin) may be more appropriately monitored and understood. DESIGN: Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients. RESULTS: Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4 kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function. CONCLUSIONS: This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype. PMID- 24225653 TI - The medaka mutation tintachina sheds light on the evolution of V-ATPase B subunits in vertebrates. AB - Vacuolar-type H(+) ATPases (V-ATPases) are multimeric protein complexes that play a universal role in the acidification of intracellular compartments in eukaryotic cells. We have isolated the recessive medaka mutation tintachina (tch), which carries an inactivating modification of the conserved glycine residue (G75R) of the proton pump subunit atp6v1Ba/vatB1. Mutant embryos show penetrant pigmentation defects, massive brain apoptosis and lethality before hatching. Strikingly, an equivalent mutation in atp6v1B1 (G78R) has been reported in a family of patients suffering from distal renal tubular acidosis (dRTA), a hereditary disease that causes metabolic acidosis due to impaired kidney function. This poses the question as to how molecularly identical mutations result in markedly different phenotypes in two vertebrate species. Our work offers an explanation for this phenomenon. We propose that, after successive rounds of whole-genome duplication, the emergence of paralogous copies allowed the divergence of the atp6v1B cis-regulatory control in different vertebrate groups. PMID- 24225654 TI - Recognition of the protein kinase AVRPPHB SUSCEPTIBLE1 by the disease resistance protein RESISTANCE TO PSEUDOMONAS SYRINGAE5 is dependent on s-acylation and an exposed loop in AVRPPHB SUSCEPTIBLE1. AB - The recognition of pathogen effector proteins by plants is typically mediated by intracellular receptors belonging to the nucleotide-binding leucine-rich repeat (NLR) family. NLR proteins often detect pathogen effector proteins indirectly by detecting modification of their targets. How NLR proteins detect such modifications is poorly understood. To address these questions, we have been investigating the Arabidopsis (Arabidopsis thaliana) NLR protein RESISTANCE TO PSEUDOMONAS SYRINGAE5 (RPS5), which detects the Pseudomonas syringae effector protein Avirulence protein Pseudomonas phaseolicolaB (AvrPphB). AvrPphB is a cysteine protease that specifically targets a subfamily of receptor-like cytoplasmic kinases, including the Arabidopsis protein kinase AVRPPHB Susceptible1 (PBS1). RPS5 is activated by the cleavage of PBS1 at the apex of its activation loop. Here, we show that RPS5 activation requires that PBS1 be localized to the plasma membrane and that plasma membrane localization of PBS1 is mediated by amino-terminal S-acylation. We also describe the development of a high-throughput screen for mutations in PBS1 that block RPS5 activation, which uncovered four new pbs1 alleles, two of which blocked cleavage by AvrPphB. Lastly, we show that RPS5 distinguishes among closely related kinases by the amino acid sequence (SEMPH) within an exposed loop in the C-terminal one-third of PBS1. The SEMPH loop is located on the opposite side of PBS1 from the AvrPphB cleavage site, suggesting that RPS5 associates with the SEMPH loop while leaving the AvrPphB cleavage site exposed. These findings provide support for a model of NLR activation in which NLR proteins form a preactivation complex with effector targets and then sense a conformational change in the target induced by effector modification. PMID- 24225655 TI - Augmentation of LPS-induced vascular endothelial cell growth factor production in macrophages by transforming growth factor-beta1. AB - The effect of LPS on the production of vascular endothelial growth factor (VEGF) was examined using RAW 264.7 macrophage cells. LPS induced VEGF production in RAW 264.7 cells and mouse peritoneal cells. LPS induced VEGF production via the expression of hypoxia inducible factor-1alpha and LPS-induced VEGF production was dependent on the activation of p38 MAPK and NF-kappaB activation. Transforming growth factor (TGF)-beta1 augmented LPS-induced VEGF production, although TGF beta1 alone did not induce VEGF production. The augmentation of LPS-induced VEGF production by TGF-beta1 was inhibited by a p38 MAPK inhibitor and was correlated with the phosphorylation of Smad3. The enhancing effect of TGF-beta1 on LPS induced VEGF production was observed in vivo in the skin lesions of mice receiving a subcutaneous injection of LPS. Taken together, it is suggested that LPS induced the VEGF production in macrophages and that it was augmented by TGF beta1 in vitro and in vivo. PMID- 24225656 TI - The acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines and their antimicrobial activity. AB - The synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines using acidic conditions, namely, a mixture of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA), is described. This methodology resulted in the synthesis of fifteen 7-azaindoles, with most containing substituents at the 2- and 5 positions. The majority of these were tested for antimicrobial activity against a range of bacteria and yeasts. The 7-azaindoles displayed the best activity against the yeasts, particularly against Cryptococcus neoformans, where activities as low as 3.9 MUg ml(-1) were observed. PMID- 24225658 TI - Comparison of different multielement techniques for analysis of mosses used as biomonitors. AB - Mosses are used as biomonitors on a regular basis to study trends in the atmospheric deposition of trace elements in Norway. In this paper the analytical scheme used so far, based on a combination of instrumental neutron activation analysis and atomic absorption spectrometry (INAA/AAS) is compared with inductively coupled plasma emission spectrometry (ICP-ES) and inductively coupled plasma mass spectrometry (ICP-MS). ICP-ES provided satisfactory data for nearly 20 elements, but detection limits were inadequate for some elements of importance. For ICP-MS quantitative data were obtained for 33 elements including the heavy metals of key interest in air pollution studies. In most cases where comparison was possible the ICP-MS data compared favourably with data obtained by the reference scheme or by ICP-ES. On the basis of this study ICP-MS is considered to be an equivalent alternative to INAA/AAS in multielement studies using mosses as biomonitors. In addition ICP-MS offers some promise for the study of elements such as Be, Ga, Mo, Te, Tl, and Bi, for which very little information exists regarding their behaviour as air pollutants. PMID- 24225657 TI - A novel renal epithelial cell in vitro assay to assess Candida albicans virulence. AB - Candida albicans, an opportunistic fungal pathogen, can cause severe systemic infections in susceptible patient groups. Systemic candidiasis is mainly studied in the mouse intravenous challenge model, where progressive infection correlates with increased early renal chemokine levels. To develop a new in vitro assay to assess C. albicans virulence, which reflects the events occurring in the murine infection model, renal M-1 cortical collecting duct epithelial cells were evaluated as the early producers of cytokines in response to C. albicans. We show that renal epithelial cells respond only to live C. albicans cells capable of forming hyphae, producing chemokines KC and MIP-2, with levels correlating with epithelial cell damage. By assaying epithelial cell responses to strains of known virulence in the murine intravenous challenge model we demonstrate that renal epithelial cells can discriminate between virulent and attenuated strains. This simple, novel assay is a useful initial screen for altered virulence of C. albicans mutants or clinical isolates in vitro and provides an alternative to the mouse systemic infection model. PMID- 24225659 TI - Temporal changes in blood lead levels of hazardous waste workers in New Jersey, 1984-1987. AB - The blood lead levels of 568 New Jersey hazardous waste workers were determined at least once in the period 1984-1987. Workers almost always wore protective clothing in the field, which should have prevented exposure to lead. Therefore, despite their occupation, these workers are probably representative of the New Jersey suburban population in the mid-1980s. Blood lead levels ranged from 2.0 20.7 ug/dL, with an arithmetic mean value of 5.8 ug/dL, representing a decline from levels measured a decade earlier, but there was no clear change over the four years of the study. Blood lead levels increased with age of the worker up to age 60. Women showed lower levels than men in every age group. PMID- 24225660 TI - Heavy metals in the SPM of air in the environment surrounding a ferro-alloy industrial plant in India. AB - Prices for ferro-alloys have hardened due to the closure of plants in developed countries on account of increasingly stringent pollution control legislation, resulting in a higher cost of production. A ferro-alloy industry with a capacity of 80000 MT per annum was selected to study the nature of pollution. Because of the objectionable nature of polluting air in and around the plant it was located in a rural area where there was no other industry. The area was agriculturally active and there was no effective control system for this plant.The quality of ambient air around the plant site is discussed in this paper along with the meteorological conditions. The maximum concentration of suspended particulate matter (SPM) was 768 ug/NM(3) downwind of the plant, minimum 184 ug/NM(3), and the average was more than 446 ug/NM(3). The presence of heavy metals, viz. Fe, Mn, Cr and Pb, was also assessed. The concentration of Fe was 50 ug/NM(3) downwind and 10 ug/NM(3) upwind. The concentration of other metals followed a similar trend. PMID- 24225661 TI - Cadmium, zinc and total mercury levels in the tissues of several fish species from La Plata river estuary, Argentina. AB - A survey of the concentrations of heavy metals - cadmium, zinc and total mercury in the tissues of fifteen fish species from Samborombon Bay, La Plata river estuary, in Argentina, has been carried out. Liver appeared to be the main organ accumulating cadmium and zinc, while both liver and muscle showed a similar ability for accumulating mercury. The bioaccumulation process was verified for the three metals analyzed, even though low concentrations have been determined. The biomagnification process of the metals studied was not verified in this environment. The highest metal concentrations were recorded in Mugil liza, and particulate matter and sediments - which are closely related to its trophic and ecological habits - seemed to be the main source of metals for this species. Both Micropogonias furnieri and Mugil liza were recognized as possible indicator species for future monitoring programmes for heavy metals in Samborombon Bay. Considering the present results, this area of La Plata river estuary is characterized as a non-polluted environment. PMID- 24225662 TI - Coral lipids and environmental stress. AB - Environmental monitoring of coral reefs is presently limited by difficulties in recognising coral stress, other than by monitoring coral mortality over time. A recent report described an experiment demonstrating that a measured lipid index declined in shaded corals. The technique described might have application in monitoring coral health, with a decline in coral lipid index as an indicator of coral stress. The application of the technique as a practical monitoring tool was tested for two coral species from the Great Barrier Reef. Consistent with the previous results, lipid index for Pocillopora damicornis initially declined over a period of three weeks in corals maintained in filtered seawater in the dark, indicating possible utilization of lipid stored as energy reserves. However, lipid index subsequently rose to near normal levels. In contrast, lipid index of Acropora formosa increased after four weeks in the dark in filtered seawater. The results showed considerable variability in lipid content between samples from the same colony. Results were also found to be dependent on fixation times and sample weight, introducing potential error into the practical application of the technique. The method as described would be unsuitable for monitoring environmental stress in corals, but the search for a practical method to monitor coral health should continue, given its importance in coral reef management. PMID- 24225663 TI - Sulphate-sulphur levels of topsoils related to atmospheric sulphur dioxide pollution. AB - Sulphate-sulphur levels were determined in topsoils from areas of varying vehicular traffic densities, population densities and industrial activities in Ibadan City, Nigeria. The factors of traffic and population densities, as well as industrial activities, had been shown to correlate positively with ambient sulphur dioxide levels.The soil-SO 4 (=) levels correlated positively with gradients in the factors tested. Vehicular traffic density variations had the most pronounced and significant effect on the SO 4 (=) level trend. The results indicate that soil-SO 4 (=) levels may be indirectly empirically related to ambient sulphur dioxide levels derived from diffuse sources. PMID- 24225664 TI - Interspecies comparison of lichens as biomonitors of trace-element air pollution. AB - The linearity of the interspecies relation between the elemental contents in Parmelia sulcata and Lecanora conizaeoides, sampled in a polluted area, was examined by the function y=az+b and yz (-1)=a+bz (-1), with y and z being the elemental content in Parmelia and Lecanora, respectively. For As, Co, V and Zn significant positive a and b values were found, allowing interspecies calibration. For Br, Cd, Cr, Fe, La, Sb, Se and W the a values were zero and the b values were positive, indicating saturation of Parmelia and thus ruling out interspecies calibration. For Cu a part of the data set showed saturation effects in Lecanora. The results showed that the average concentration ratio could not be used for intercalibration purposes, because the concentration ratios were dependent on the concentrations. PMID- 24225665 TI - Ground level nitrogen dioxide concentrations in the rural Waikato Valley, New Zealand. AB - Ground level nitrogen dioxide (NO2) concentrations have been measured for one year over an area of 400 square kilometres in rural New Zealand using an array of 21 sites. Three passive samplers were exposed at each site for intervals of two weeks from August 1989 to August 1990. The exposure sites were centred around the Waikato Valley township of Huntly (population 6900). Important features of the survey area include a 1000 MW thermal power station situated on the outskirts of the town, the Waikato River and State Highway 1, a major north-south traffic route along the valley. The NO2 concentrations in the survey area ranged from below 0.1 to 10.1 ppb, with an annual average of 1.2 ppb. Seasonal variations indicate summer values about three times lower than those found in the winter. The spatial distribution of NO2 appears to be related to contributions from State Highway 1. PMID- 24225666 TI - Left lower quadrant mass. PMID- 24225667 TI - A golden future in medicinal inorganic chemistry: the promise of anticancer gold organometallic compounds. AB - From wedding rings on fingers to stained glass windows, by way of Olympic medals, gold has been highly prized for millennia. Nowadays, organometallic gold compounds occupy an important place in the field of medicinal inorganic chemistry due to their unique chemical properties with respect to gold coordination compounds. In fact, several studies have proved that they can be used to develop highly efficient metal-based drugs with possible applications in the treatment of cancer. This Perspective summarizes the results obtained for different families of bioactive organometallic gold compounds including cyclometallated gold(iii) complexes with C,N-donor ligands, gold(I) and gold(I/III) N-heterocyclic (NHC) carbene complexes, as well as gold(I) alkynyl complexes, with promising anticancer effects. Most importantly, we will focus on recent developments in the field and discuss the potential of this class of organometallic compounds in relation to their versatile chemistry and innovative mechanisms of action. PMID- 24225668 TI - Fish oil supplementation reduces markers of oxidative stress but not muscle soreness after eccentric exercise. AB - Due to the potential anti-inflammatory properties of fish-derived long chain n-3 fatty acids, it has been suggested that athletes should regularly consume fish oils-although evidence in support of this recommendation is not clear. While fish oils can positively modulate immune function, it remains possible that, due to their high number of double bonds, there may be concurrent increases in lipid peroxidation. The current study aims to investigate the effect of fish oil supplementation on exercise-induced markers of oxidative stress and muscle damage. Twenty males underwent a 6-week double-blind randomized placebo controlled supplementation trial involving two groups (fish oil or placebo). After supplementation, participants undertook 200 repetitions of eccentric knee contractions. Blood samples were taken presupplementation, postsupplementation, immediately, 24, 48, and 72 hr postexercise and muscle soreness/maximal voluntary contraction (MVC) assessed. There were no differences in creatine kinase, protein carbonyls, endogenous DNA damage, muscle soreness or MVC between groups. Plasma thiobarbituric acid reactive substances (TBARS) were lower (p < .05) at 48 and 72 hr post exercise and H2O2 stimulated DNA damage was lower (p < .05) immediately postexercise in the fish oil, compared with the control group. The current study demonstrates that fish oil supplementation reduces selected markers of oxidative stress after a single bout of eccentric exercise. PMID- 24225669 TI - Non-covalent surface modification of boron nitride nanotubes for enhanced catalysis. AB - Boron nitride nanotubes were functionalized with microperoxidase-11 in aqueous media, showing improved catalytic performance due to a strong electron coupling between the active centre of microperoxidase-11 and boron nitride nanotubes. PMID- 24225670 TI - A dramatic platform for oxygen reduction reaction based on silver nanoclusters. AB - We report a high-yield strategy for the synthesis of very small silver nanoclusters (2 to 5 silver atoms) formed from conventional silver salts and scaffolds as high-performance catalysts for oxygen reduction reaction (ORR). The work demonstrates that Ag NCs are excellent catalysts for ORR and show great potential in alkaline fuel cells. PMID- 24225671 TI - Tomato resistance to Alternaria stem canker: localization in host genotypes and functional expression compared to non-host resistance. AB - The Alternaria stem canker resistance locus (Asc-locus), involved in resistance to the fungal pathogen Alternaria alternata f. sp. lycopersici and in insensitivity to host-specific toxins (AAL-toxins) produced by the pathogen, was genetically mapped on the tomato genome. Susceptibility and resistance were assayed by testing a segregating F2 population for sensitivity to AAL-toxins in leaf bioassays. Linkage was observed to phenotypic markers solanifolium and sunny, both on chromosome 3. For the Asc-locus, a distance of 18 centiMorgan to solanifolium was calculated, corresponding to position 93 on chromosome 3. This map position of the resistance locus turned out to be the same in three different resistant tomato accessions, one Dutch and two American, that are at least 40 years apart. AAL-toxin sensitivity in susceptible and resistant tomato genotypes was compared with AAL-toxin sensitivity in a non-host Nicotiana tabacum during different levels of plant cell development. In susceptible and resistant tomato genotypes, inhibitory effects were demonstrated at all levels, except for leaves of resistant genotypes. However, during pollen and root development, inhibitory effects on susceptible genotypes were larger than on resistant genotypes. In the non-host Nicotiana tabacum, hardly any effects of AAL-toxins were demonstrated. Apparently, a cellular target site is present in tomato, but not in Nicotiana tabacum. It was concluded that three levels of AAL-toxin sensitivity exist: (1) a susceptible host sensitivity, (2) a resistant host sensitivity, (3) a non-host sensitivity, and that the resistance mechanism operating in tomato is different from that operating in Nicotiana tabacum. PMID- 24225672 TI - Internal estimation and controlled selection with applications to sheep. AB - This paper examines the relationship of economic weights, a i, with a general economic value surface. It is inferred that the a i may vary across the population, as they can depend on the mean vector for the characters of interest. It is shown how these ideas extend to provide simple mechanisms for controlled selection. The problem of estimation is raised, and it is suggested that the procedures can be efficiently implemented, even in small populations, by a system of 'internal' parameter estimation. This makes the entire selection programme independent of externally generated estimates of genetic parameters. PMID- 24225673 TI - A comparison of anther and microspore culture as a breeding tool in Brassica napus. AB - A direct comparison of microspore culture and anther culture was made in Brassica napus using F1 crosses of Regent (canola) by Golden (rapeseed), and their reciprocals, as well as a hybrid between Reston and a highly embryogenic, canola quality breeding line (G231) as donor plants. The study confirmed that microspore culture can be ten times more efficient than anther culture for embryo production. Embryo yields from cultures initiated from the Reston x G231 were four-fold greater than those initiated from the Regent x Golden crosses, and significant differences were also detected among cultures initiated from the different Regent x Golden crosses. These results illustrate the influence that donor plant genotype has on embryo production. However, superior embryogenic potential among donor material was not always coincident with superior plant production. The average haploid-todiploid ratio in microspore-derived regenerates was 2?1 for the population obtained from the Regent x Golden crosses but 1?1 for the Reston x G231 cross. For both types of material, the frequency of diploids increased upon repeated cycles of explanting. A field study showed that there were no differences between the populations of anther-derived and microspore derived spontaneous diploid and doubled haploid lines, with respect to the days required for them to flower or to mature. The information is valuable for canola breeding programs considering the use of haploidy. PMID- 24225674 TI - Variation in outcrossing rate and population genetic structure of Clarkia tembloriensis (Onagraceae). AB - Outcrossing rate estimates for eight accessions of Clarkia tembloriensis indicate that this annual plant species has a wide interpopulational range of outcrossing rate ([Formula: see text]). Populations' t estimates were significantly correlated with observed heterozygosity and mean number of alleles per locus. Estimated fixation indices, [Formula: see text], for most populations were very close to their expected values, Feq, for a given [Formula: see text] Nei's gene diversity statistics showed that the group of outcrossing populations have more total genetic variation and less differentiation among populations than does the group of selfing populations. These results indicate that the breeding system of C. tembloriensis has had a strong influence on the amount and distribution of genetic variation within and among its populations. PMID- 24225675 TI - An isozyme marker for resistance to race 3 of Fusarium oxysporum f. sp. lycopersici in tomato. AB - The inheritance and the linkage relationship of resistance to race 3 of Fusarium oxysporum f. sp. lycopersici derived from Lycopersicon pennellii (LA 716) were analyzed in an interspecific backcross to L. esculentum. Progeny from each backcross (BC1) individual were in-oculated with race 3 and their response was measured according to a visual rating system; progeny responses were used to calculate a mean disease rating for each BC1 individual. The frequency distribution of the disease ratings was bimodal, indicating that resistance to race 3 was controlled by one major locus. Linkage analysis of this locus proceeded in two steps. Initially, disease ratings were compared between homozygotes and heterozygotes at each of 17 segregating marker enzyme loci. Highly significant differences were detected for the chromosome segment marked by the Got-2 locus on chromosome 7. This indicated that Got-2 was linked to the race 3 resistance gene, designated I-3; this gene accounted for the observed bimodal distribution of BC1 disease ratings. In the second step, the genotype of each BC1 individual at the I-3 locus was determined using cluster analysis of the disease ratings; a test for independent assortment between I-3 and Got-2 revealed strong linkage, with an estimated map distance of 2.5 centiMorgans. Additional evidence for this linkage was obtained from the analysis of five breeding lines previously selected for resistance to race 3 solely on the basis of inoculations; all five showed co-selection for Got-2. The Got-2 locus is proposed as a selectable marker to expedite the transfer of race 3 resistance to commercial tomato cultivars. PMID- 24225676 TI - RFLP-based genetic maps of wheat homoeologous group 7 chromosomes. AB - Restriction fragment length polymorphism (RFLP) mapping was attempted using 18 cDNA clones, 14 anonymous and 4 of known function, which had been shown to have homologous DNA sequences on the group 7 chromosomes of wheat. The loci identified by these probes have been mapped on one or more chromosomes in this homoeologous group using linkage data derived from various F2, random inbred, doubled haploid and single chromosome recombinant populations. The maps also include three isozyme loci, five disease resistance loci, two anthocyanin pigment loci and a vernalisation response locus. The mapping data have been used to determine the extent of map co-linearity over the A, B and D genomes, the degree of RFLP variability in the three genomes and the relative efficiency of various restriction enzymes in detecting RFLPs in wheat. The strategy for future mapping in wheat, particularly the use of "alien" genomes or segments, such as that from Aegilops ventricosa used here, is discussed. PMID- 24225677 TI - Protein mapping and genome expression variations in the basidiomycete Agrocybe aegerita. AB - A procedure suitable for the extraction and mapping of total proteins from the basidiomycete, Agrocybe aegerita, was developed. A. aegerita mycelia were fragmented either with a Dangoumeau grinder, an X-press bomb or a sonicator and the efficiency of these three disruption methods were compared. The extraction buffer composition was optimized to avoid proteolytic activities. 2D-SDS-PAGE analysis of protein extracts showed that the rate of reproducibility depending on extractions and electrophoretic separations was always greater than 96% for all strains. The differences in efficiency observed between the breaking procedures indicate that the A. aegerita cell wall is more mechanically resistant than that of other basidiomycetes. The efficient action of protease inhibitors (PMSF and SDS) showed that A. aegerita mycelia contains numerous and/or highly active proteases. Reproducibility of protein extraction and separation methods allowed the establishment and the comparison of standard maps. Qualitative and quantitative variations in gene products between a wild dikaryotic strain and 11 homokaryotic strains from its progeny were examined. The genetic diversity, determined by comparing the distribution of proteic variations in 11 homokaryons from the same progeny, was comparable to that observed between co-isogenic homokaryons of another basidiomycete. PMID- 24225678 TI - Transfer of resistance against Phoma lingam to Brassica napus by asymmetric somatic hybridization combined with toxin selection. AB - Irradiated mesophyll protoplasts from nine different accessions of B. juncea, B. nigra and B. carinata, all resistant to Phoma lingam, were used as gene donors in fusion experiments with hypocotyl protoplasts isolated from B. napus as the recipient. A toxin, sirodesmin PL, was used to select those fusion products in which the resistant gene(s) was present. In the fusion experiments different gene donors, various irradiation dosages and toxin treatments were combined. Symmetric and asymmetric hybrid plants were obtained from the cell cultures with and without toxin selection. Isozymes were used to verify hybrid characters in the symmetric hybrids, whereas two DNA probes were used to identify donor-DNA in the asymmetric hybrids. Resistance to P. lingam was expressed in all symmetric hybrids, and in 19 of 24 toxin-selected asymmetric hybrids, while all the unselected asymmetric hybrids were susceptible. PMID- 24225679 TI - Effects of auxin and cytokinin on induction of sister chromatid exchanges in cultured cells of wheat (Triticum aestivum L.). AB - In order to know the mutagenic effects of synthetic auxins (NAA, 2,4-D, and 2,4,5 T) and a cytokinin (kinetin) in vitro, sister chromatid exchanges (SCEs) were analyzed in cultured cells of a hexaploid wheat (Triticum aestivum L.). In the MS medium supplemented with 2.0 mg/l 2,4-D, the mean number of SCEs per cell was 15.2, and per pg of DNA, 0.42. No significant effect was found in the treatments of NAA or 2,4-D at concentrations of 0.5-10.0 mg/l, whereas more than 2.0 mg/l of 2,4,5-T induced dramatic increases of SCEs. Kinetin itself had no significant effect on SCE induction, but there was a tendency that SCEs induced by 2,4,5-T were suppressed by kinetin. PMID- 24225680 TI - Microspore mutagenesis and selection: Canola plants with field tolerance to the imidazolinones. AB - In vitro microspore mutagenesis and selection was used to produce five fertile double-haploid imidazolinone-tolerant canola plants. The S2 plants of three of the mutants were resistant to at least the field-recommended levels of Assert and Pursuit. One mutant was tolerant to between five and ten times the field recommended rates of Pursuit and Scepter. Two semi-dominant mutants, representing two unlinked genes, were combined to produce an F1 hybrid which was superior in imidazolinone tolerance to either of the heterozygous mutants alone. Evaluation of the mutants under field conditions indicated that this hybrid and the original homozygous mutants could tolerate at least two times the field-recommended rates of Assert. The field results indicated the mutants were unaffected in seed yield, maturity, quality and disease tolerance. These genes represent a potentially valuable new herbicide resistance system for canola, which has little effect on yield, quality or maturity. The mutants could be used to provide tolerance to several imidazolinones including Scepter, Pursuit and Assert. PMID- 24225681 TI - Factors affecting transient gene expression in electroporated black spruce (Picea mariana) and jack pine (Pinus banksiana) protoplasts. AB - Methods were developed for transient gene expression in protoplasts of black spruce (Picea mariana) and jack pine (Pinus banksiana). Protoplasts were isolated from embryogenic suspension cultures of black spruce and from non-embryogenic suspensions of jack pine. Using electroporation, transient expression of the chloramphenicol acetyltransferase (CAT) gene was assayed and shown to be affected by the cell line used, by voltage, temperature, and by the plasmid concentration and conformation. Increasing the plasmid DNA concentration (0-150MUg ml(-1)) resulted in higher levels of transient CAT expression. In jack pine, linearized plasmid gave 2.5 times higher levels of CAT enzyme activity than circular. Optimal voltage varied for each cell line of the two species within the range 200 350 V cm(-1) (960 MUF). A heat shock treatment of protoplasts for 5 min at 45 degrees C resulted in enhanced CAT gene expression for both species. PMID- 24225682 TI - Biochemical genetic markers in sugarcane. AB - Isozyme variation was used to identify biochemical markers of potential utility in sugarcane genetics and breeding. Electrophoretic polymorphism was surveyed for nine enzymes among 39 wild and noble sugarcane clones, belonging to the species most closely related to modern varieties. Up to 114 distinct bands showing presence versus absence type of variation were revealed and used for qualitative characterization of the materials. Multivariate analysis of the data isolated the Erianthus clone sampled and separated the Saccharum spontaneum clones from the S. robustum and S. officinarum clones; the latter two were not differentiated from one another. The analysis of self-progenies of a 2n=112 S. spontaneum and of a commercial variety showed examples of mono- and polyfactorial segregations. Within the progeny of the variety, co-segregation of two isozymes frequent in S. spontaneum led to them being assigned to a single chromosome initially contributed by a S. spontaneum donor. This illustrates how combined survey of ancestral species and segregation analysis in modern breeding materials should permit using the lack of interspecific cross-over to establish linkage groups in a sugarcane genome. PMID- 24225683 TI - System of pleiotropic polygenes in the Cucurbitacea Ecballium elaterium (L.) Rich. related to durability and size of plant. AB - The statistical association between the characters "life durability of plant" and "size of plant" observed in a set of samples - cultivated forming a system of randomly balanced incomplete blocks - and corresponding to filial generations (pure, hybrid or backcross) from hybridization between the monoecious subspecies and the dioecious subspecies of the Cucurbitacea Ecballium elaterium (L.) Rich, respectively, is in concordance with the hypothesis that the system of polygenes governing the life durability of the plant in this species and the system of polygenes governing the size of the plants belong to the same system of polygenes. This system of pleiotropic polygenes governs the size and life durability of the plants at the same time. PMID- 24225684 TI - Transmission of organelles in triploid hybrids produced by gametosomatic fusions of two Nicotiana species. AB - Gametosomatic hybrids produced by the fusion of microspore protoplasts of Nicotiana tabacum Km(+)Sr(+) with somatic cell protoplasts of N. rustica were analysed for their organelle composition. For the analysis of mitochondrial (mt)DNA, species-specific patterns were generated by Southern hybridization of restriction endonuclease digests of total DNA and mtDNA with four DNA probes of mitochondrial origin: cytochrome oxidase subunit I, cytochrome oxidase subunit II, 26s rDNA and 5s-18s rDNA. Of the 22 hybrids analyzed, some had parental-type pattern for some probes and novel-type for the others, indicating interaction between mtDNA of the two parent species. For chloroplast (cp)DNA analysis, species-specific patterns were generated by Southern hybridization of restriction endonuclease digests of total DNA with large subunits of ribulose bisphosphate carboxylase and cpDNA as probes. All the hybrids had N. rustica-specific patterns. Hybrids were not resistant to streptomycin, a trait encoded by the chloroplast genome of N. tabacum. In gametosomatic fusions of the two Nicotiana species, mitochondria but not the chloroplasts are transmitted from the parent contributing microspore protoplasts. PMID- 24225685 TI - Spatial and temporal expression of the two sucrose synthase genes in maize: immunohistological evidence. AB - We describe the spatial and temporal immunohistological distributions of the two sucrose synthases, SS1 and SS2, encoded by the Sh and Sus genes, respectively, in different parts of the maize plant. The two similar isozymes were differentially localized in developing endosperm cells through the combined uses of a shrunken (sh) mutant lacking the SS1 protein and the SS1 and SS2 antisera. The accumulation of SS1 protein always coincided with starch deposition in the Sh endosperm cells, whereas in the sh endosperm, the centrally located cells were lost at or during the most critical phase of starch biosynthesis. The SS2 specific cells, including aleurone layer and the basal endosperm transfer cells in both genotypes, were not associated with detectable starch deposition. Such heterogeneity was indicative of two cell types separable by gene expression, and of differential in vivo roles of the two isozymes in the endosperm. In young roots, the expression of both SS encoding genes was predominantly in the vascular cylinder region. These data fulfill a previous prediction, based on the genetic analyses, that the expression of the SS genes is spatially and/or temporally separated in endosperm cells but not in root cells. PMID- 24225686 TI - Genetic parameters and selection efficiency using part-records for production traits in strawberries. AB - The efficiency of selection for yield and fruit size using parts of the complete season record was evaluated using data collected for individual strawberry seedlings (Fragaria x annanasa) in four genetic tests. Part-records were generated for each trait using cumulative weekly sums, and these were compared with complete records to assess the value of extended data collection. In addition, part-records were generated using data from alternate weeks of harvest. Scoring separate sets of seedlings in alternate weeks was assumed to allow a doubling of the unselected population size, halving the selection proportion and increasing selection intensity. Heritabilities estimated for part-records were often larger for mid-season cumulative part-records than for the complete-season records. Seasonal patterns for broad-sense and narrow-sense heritabilities differed, suggesting temporal expression of genes that condition yield and fruit size. Predicted genetic gains were largest using cumulative part-records between 4 and 12 weeks of the 15-week season, depending on trait and breeding objective (breeding value versus clonal value), with 8-9 weeks as a reasonable compromise. Selection using alternate-weeks records was identified as an efficient alternative to selection using total complete-season records. Superiority of the alternate-weeks option depends on the balance between increased selection intensity and decreased individual genetic information, and will differ for specific traits and program designs. PMID- 24225687 TI - Non-additive gene effects in populations under different methods of selection. AB - The genetic parameters of two quantitative traits, 13-day larval weight and pupal weight, in Tribolium populations developed by reciprocal recurrent selection (RRS) and by within-line purebred selection (WLS) were compared each with the other and also with the parameters of the unselected base populations using the genetic model of Carbonell, Nyquist and Bell. The variability for two and three way crosses of inbred lines derived from "companion" populations (two strains, breeds, or varieties used for a terminal cross or hybrid) was analyzed into genetic effects: autosomal additivity ((*) g), autosomal heterosis ((*) s), sex linked additivity (L), sex-linked heterosis (LL), general maternal (m), specific maternal or reciprocal (r), additive by additive epistasis (aa), and deviations from the model due, among other causes, to higher order epistasis (dev). One series of crosses involved companion populations with diverse origins. For contrast, a second series of crosses involved companion populations originating from a common heterogenous base population. For the heterotic trait larval weight, (*) g and (*) s effects were equally important and accounted for over 50% of the total variation. The aa epistasis contributed another 20% and was followed in importance by higher order epistasis and general maternal effects. For the more highly heritable trait, pupal weight, (*) g effects were most important with (*) s, aa, and m effects having smaller but significant influences. Sex-linked and reciprocal effects were statistically significant for many crosses, but they were relatively unimportant overall. In general, the unselected base populations showed higher (*) g variation than either RRS or WLS populations with the reverse true for (*) s effects. In agreement with theoretical expectations, RRS was more effective than WLS in exploiting (*) s effects. The aa epistatic effects for larval weight were of major importance in the unselected populations, but RRS and WLS did not differ significantly for exploiting superior aa gene combinations. Companion populations with diverse origins revealed significantly larger variation due to (*) g and (*) s effects in crosses than did populations initiated from a common heterogeneous base. PMID- 24225688 TI - Characterization of proteins associated with self-incompatibility in Solanum tuberosum. AB - The gametophytic self-incompatibility system of Solarium tuberosum is controlled by a single locus, designated as the S-locus. Protein extracts from potato styles of defined S-genotypes have been analysed by two-dimensional gel electrophoresis, and found to contain a group of basic glycoproteins. Each genetically determined allele S 1 to S 4 was associated with the presence of one of a number of these polypeptides differing slightly in isoelectric points (in the range 8.3->9.1) and/or apparent molecular weight (ranging from 23,000 to 29,000). Two abundant basic polypeptides, one of which is apparently not glycosylated, were present in all genotypes examined. Amino-terminal protein sequence determinations revealed homologies of the S. tuberosum stylar proteins S2, S3 and S4 with SI-associated polypeptides from Nicotiana alata and Lycopersicon peruvianum. With an oligonucleotide generated to the potato-S2 N-terminal protein sequence, it was possible to detect a style-specific RNA species of ~920 nucleotides. The oligonucleotide also behaved as an allele-specific probe when hybridized to total RNA of different S-genotypes. PMID- 24225689 TI - Dialect-I, species-specific repeated DNA sequence from barley, Hordeum vulgare. AB - Dialect-1, species-specific repetitive DNA sequence of barley Hordeum vulgare, was cloned and analysed by Southern blot and in situ hybridization. Dialect-1 is dispersed through all barley chromosomes with copy number 5,000 per genome. Two DNA fragments related to Dialect-1 were revealed in lambda phage library, subcloned and mapped. All three clones are structurally heterogenous and it is suggested that the full-length genomic repeat encompassing Dialect-1 is large in size. The Dialect-1 DNA repeat is represented in the genomes of H. vulgare and ssp. agriocrithon and spontaneum in similar form and copy number; it is present in rearranged form with reduced copy number in the genomes of H. bulbosum and H. murinum, and it is absent from genomes of several wild barley species as well as from genomes of wheat, rye, oats and maize. Dialect-1 repeat may be used as a molecular marker in taxonomic studies and for identification of barley chromosomes in interspecies hybrids. PMID- 24225690 TI - Efficient transformation of potato (Solanum tuberosum L.) using a binary vector in Agrobacterium rhizogenes. AB - We transformed three potato (Solanum tuberosum L.) genotypes by using A. rhizogenes or a mixture of A. rhizogenes and A. tumefaciens. Inoculations of potato stem segments were performed with Agrobacterium rhizogenes AM8703 containing two independent plasmids: the wild-type Ri-plasmid, pRI1855, and the binary vector plasmid, pBI121. In mixed inoculation experiments, Agrobacterium rhizogenes LBA1334 (pRI1855) and Agrobacterium tumefaciens AM8706 containing the disarmed Ti-plasmid (pAL4404) and the binary vector plasmid (pBI121) were mixed in a 1?1 ratio. The T-DNA of the binary vector plasmid pBI121 contained two marker genes encoding neomycin phosphotransferase, which confers resistance to kanamycin, and beta-glucuronidase. Both transformation procedures gave rise to hairy roots on potato stem segments within 2 weeks. With both procedures it was possible to obtain transformed hairy roots, able to grow on kanamycin and possessing beta-glucuronidase activity, without selection pressure. The efficiency of the A. rhizogenes AM8703 transformation, however, was much higher than that of the "mixed" transformation. Up to 60% of the hairy roots resulting from the former transformation method were kanamycin resistant and possessed beta glucuronidase activity. There was no correlation between the height of the kanamycin resistance and that of the beta-glucuronidase activity in a root clone. Hairy roots obtained from a diploid potato genotype turned out to be diploid in 80% of the cases. Transformed potato plants were recovered from Agrobacterium rhizogenes AM8703-induced hairy roots. PMID- 24225691 TI - Segregation of genetic markers in the two-spored secondarily homothallic basidiomycete Coprinus bilanatus. AB - Secondarily homothallic basidiomycetes, of which the cultivated mushroom Agaricus bisporus is an example, produce both self-fertile and non self-fertile spores. The random migration of nuclei from the basidia to give binucleate spores provides the simplest explanation for the regulation of breeding behaviour in this group of fungi. To test the predictions of the random migration hypothesis, the segregation of mating-type, auxotrophy and antimetabolite resistance has been determined in the secondarily homothallic ink-cap fungus, Coprinus bilanatus. In 41 of a total of 56 spore progenies tested, the segregation ratios conformed to the predictions of the random migration hypothesis. Poor fits to the predicted ratios were, in many instances, associated with an adenine auxotrophy. On the basis of the data reported, random migration can be regarded as the primary control of secondary homothallism. PMID- 24225692 TI - Reconceptualizing schizophrenia. AB - The recent emphasis for research on psychiatric disorders focuses on supposed underlying processes and their biological elements. Although such a direction may be fruitful, it would be a mistake to ignore more integrated approaches for understanding the mysteries of schizophrenia or other psychiatric disorders. The complexity of the biopsychosocial paradigm should not lead to ignoring its potential value for understanding these disorders. The role of subjective data other than those identified as "symptoms" is also likely to be crucial. PMID- 24225693 TI - Ultrastructure of bacteria and the proportion of Gram-negative bacteria in marine sediments. AB - Bacteria in sediments from the surface aerobic layer (0-1 cm) and a deeper anaerobic layer (20-21 cm) of a seagrass bed were examined in section by transmission electron microscopy. Bacteria with a Gram-negative ultrastructure made up 90% of bacteria in the surface layer, and Gram-positive bacteria comprised 10%. In the anaerobic zone, Gram-negative bacteria comprised 70% and Gram-positive bacteria 30% of the bacterial population. These differences were highly significant and support predictions of these proportions made from muramic acid measurements and direct counting with fluorescence microscopy. Most cells were enveloped in extracellular slime layers or envelopes, some with considerable structural complexity. The trophic value to animals of these envelopes is discussed. A unique organism with spines was observed. PMID- 24225694 TI - Evaluation of a proposed surface colonization equation usingThermothrix thiopara as a model organism. AB - The colonization equation shown below was evaluated usingThermothrix thiopara as a model organism.[Formula: see text] where: N=number of cells on surface (cells field(-1)); A = attachment rate (cells field(-1) h(-1)); M=specific growth rate (h(-1)); t=incubation period (h).Previous studies of microbial surface colonization consider attachment and growth independently. However, the proposed colonization equation integrates the effects of simultaneous attachment and growth. Using this equation, the specific growth rate ofT. thiopara was found to be 0.38+/-0.3 h(-1) during in situ colonization. Estimates ofMU were independent of incubation period after 4 h (2 generations). Shorter incubations were inadequate to produce sufficient microcolonies for accurate determination of specific growth rate. Empirical data for the time course of colonization fell within the 95% confidence interval of predicted values. The attachment rate, although assumed to be constant, was found to continuously increase with time. This increase may have been an artifact due to the continuous deposition of travertine on the surface, or may indicate the need for a function to replace A in the colonization equation. Using the exponential growth equation, the progeny of cells that attach during incubation are considered to be progeny of cells that attach initially. This erroneously inflated the growth rate by 55%. PMID- 24225695 TI - Growth and uptake kinetics of a facultatively oligotrophic bacterium at low nutrient concentrations. AB - In oligotrophic waters, not only community structure but also physiological properties of heterotrophic bacteria are influenced by the concentration of organic matter.The relationship between growth rate of two facultatively oligotrophic strains ofAeromonas sp. No. 6 andFlavobacterium sp. M1 was studied in comparison with that of two eutrophic strains ofEscherichia coli 7020 andFlavobacterium sp. M2. These strains had two or three different substrate constants (Ks values) depending on substrate concentrations: Ks values for the two former were remarkably lower than those for the two latter. For instance, Ks value forAeromonas sp. No. 6 was about 8.9MUM when substrate concentration was greater than 53MUM and about 1.1MUM when substrate concentration was less man 53MUM. InE. coli the Ks value was about 260MUM at greater than 5600MUM and about 47MUM at less than 5600MUM substrate concentration.Uptake kinetics ofAeromonas sp. grown in a medium containing 2.7 mM glutamate (H-cell) and 0.11MUM glutamate (L-cell) have been determined for the intact cells. H-cell had two distinct values of Km for glutamate assimilation and respiration, and L-cell had three distinct values of Km for glutamate assimilation and respiration: In H-cell Km of assimilation was 2.8*10(-7) M and 1.5*10(-4) M, and Km of respiration was 2.3*10( 7) M and 1.7*10(-4) M; in L-cell Km of assimilation was 7.4*10(-8) M, 8.3*10(-6) M, and 1.3*10(-4) M, and Km of respiration was 2.5*10(-7), 8.9*10(-6)M, and 1.7*10(-4) M. More than 60% of glutamate taken up by the H- and L-cells was respired when the substrate concentration was less than 10(-6) M, although at greater than 10(-6) M, 50% and 30% of glutamate was respired by H-cells and L cells, respectively. These results suggest that the facultatively oligotrophic bacteria grow with high efficiency in environments with extremely low nutrient concentration, such as oligotrophic waters of lakes and ocean, as compared with in their growth in conditions of high nutrient concentraton, such as nutrient broth. PMID- 24225696 TI - Bacterial productivity in the water column and sediments of the Georgia (USA) coastal zone: Estimates via direct counting and parallel measurement of thymidine incorporation. AB - Three methods of estimating bacterial productivity were compared using parallel samples of Atlantic Ocean water (within 0.25-15 km of the Georgia coast). The frequency-of-dividing cells (FDC) method and the [(3)H]thymidine incorporation method gave results which were strongly correlated (r=0.97), but the FDC estimates were always higher (X2 to X7) than the [(3)H]thymidine estimates. Estimates of bacterial productivity ranged from 2-4*10(8) cells.l(-1).h(-1) at 0.25 km from shore to 1-9*10(7)cells.l(-1).h(-1) at 15 km. A method involving incubation of 3-MUm filtrates and direct counting gave results that could not be easily translated into estimates of bacterial productivity. Application of the FDC method to sediment samples gave high productivity estimates, which could be not reconciled with productivity estimates based on sediment oxygen uptake. PMID- 24225697 TI - Abiotic formation of particles from extracellular organic carbon released by phytoplankton. AB - (14)C-labeled extracellular organic carbon (EOC) released by the phytoplankton in a Danish Estuary was shown immediately to form particles (>0.2MUm) when the products were added to a natural water sample. About 14%-20% of the added activity could be recovered as particles. Any bacterial assimilation of the extracellular products was thus masked. The abiotic origin of the particulate EOC was verified, and it was shown that the particle formation was due to some factors present in the estuarine water with a nominal diameter >0.2MUm. Precaution must be taken to avoid misinterpretations in studies concerning carbon flow from algae to bacteria. PMID- 24225698 TI - Further studies on respiratory rates of freshwater amoebae (Rhizopoda, Gymnamoebia). AB - The respiration rates of axenically culturedAcanthamoeba castellanii (Gymnamoebia) and of the test organismTetrahymena pyriformis (Ciliophora) were compared using both Warburg and cartesian diver respirometer techniques at 20 degrees C. Furthermore, the latter procedure was employed to measure the oxygen consumption of the amoebae,Polychaos fasciculatum, Saccamoeba limax, andAmoeba sp. The linear relationship between respiration rate and mean cell volume in amoebae was reassessed in view of these additional estimates. The importance of this regression in ecological studies is discussed. PMID- 24225699 TI - Statistical sampling of bacterial strains and its use in bacterial diversity measurement. AB - The cultural bacterial strains of two sediment samples, i.e., 260 strains, were submitted to numerical taxonomy to determine "ecological profiles." From these profiles several calculations of bacterial diversity were done with increasing number of strains (between 10 and 130). Studying 20-30 strains was sufficient to obtain a diversity of bacterial community.Number of tests could be reduced from 62 to 30 without any influence on bacterial diversity. Similarity between studied tests was shown by using numerical taxonomy. PMID- 24225700 TI - Analysis of the community structure of yeasts associated with the decaying stems of cactus. I.Stenocereus gummosus. AB - Yeast communities of decayingStenocereus gummosus were analyzed for spatial, temporal, and physiological characteristics. Analysis of random samples within plants, between plants, and between localities shows that the species proportions of the yeast community are relatively constant within plants and between localities, but that there is significant variability between rotting plants. It is suggested that the increased variability between plants represents sampling of different stages of succession. The physiological abilities of the yeast community also show a relatively constant pattern within plants and between localities yet more variability between plants.The variablity profiles of species proportions and community physiological characters are demonstrated to be correlated within and between plants. This observation is an extension of the Kluge-Kerfoot phenomenon to the level of the community. The correlation of within and between plant variability profiles is suggested to be a result of the temporal and spatial availability of resources during the stages of rotting plant succession. The community structure is thus postulated to result from a set of possible future resource states of the habitat. PMID- 24225701 TI - Yeast flora of grape berries during ripening. AB - The yeast flora associated with the surface of grapes during ripening was studied with regard to different sectors of the grape skin and the position in the bunch by means of traditional as well as more vigorous preisolation and precounting treatments. The yeast number per square centimeter of skin increases with ripening and is highest in the area immediately surrounding the stem. The cluster sector closer to the peduncle seems to constitute a favorable substrate for yeasts, hosting a resident flora about 10 and 100 times higher than the central and lower parts of the bunch, respectively.Kloeckera apiculata was the normal resident species of grapes regardless of the sector or the ripening period, and constitutes the fermenting flora of mature grapes. The ecological implications of the results of this survey are discussed. PMID- 24225702 TI - Decomposers and the fire cycle in a phryganic (East Mediterranean) ecosystem. AB - Dehydrogenase activity, cellulose decomposition, nitrification, and CO2 release were measured for 2 years to estimate the effects of a wildfire over a phryganic ecosystem. In decomposers' subsystem we found that fire mainly affected the nitrification process during the whole period, and soil respiration for the second post-fire year, when compared with the control site. Our data suggest that after 3-4 months the activity of microbial decomposers is almost the same at the two sites, suggesting that fire is not a catastrophic event, but a simple perturbation common to Mediterranean-type ecosystems. PMID- 24225703 TI - Vital staining permits isolation of calcium vesicles from the green alga Mougeotia. AB - The calcium vesicles of the green alga Mougeotia (G. Wagner and R. Rossbacher, 1980, Planta 149, 298-305) were isolated for characterization in vitro by fractionation of algal homogenate on sucrose density gradients. A new technique, based on vital staining by neutral red or rhodamine B, permitted isolation. Minimum dye binding to the calcium vesicles prevented desintegration, and for isolation a single, thoroughly defined centrifugation step sufficed, facilitated by the exceptionally high vesicular density of >=1.3 g. cm(-3). Neutral red in particular seems to be accumulated by the vesicles via hydrogen bonds to abundant phenolic hydroxyl groups which, reversibly bound to an as yet undefined vesicle core, may well provide coordination sites for the observed calcium binding. PMID- 24225704 TI - Immuno-gold localization of alpha-L-arabinofuranosyl residues in pollen tubes of Nicotiana alata Link et otto. AB - Immuno-gold labelling using a monoclonal antibody (PCBC3) with a primary specificity for alpha-L-arabinofuranosyl residues was used to locate these residues in pollen tubes of Nicotiana alata grown in vivo. The antibody bound to the outer fibrillar layer of the pollen-tube wall: the inner, non-fibrillar wall layer was not labelled. Cytoplasmic vesicles (0.2 MUm diameter) were also labelled. The antibody may bind to an arabinan in the pollen-tube wall. PMID- 24225705 TI - Immunocytological and chemical studies on the stromacentre-forming protein from Avena plastids. AB - The stromacentre (SC), a particular structure in the plastids of Avena, was isolated from etioplasts of Avena sativa by density gradient centrifugation and then analyzed and compared with ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBPCase) from A. sativa, with pyrenoids of Chlorella vulgaris and with the "stromacentre" of Opuntia. Purified SC-elements consisted of protein subunits with a relative molecular weight of 63 kDa, different from the isolated RuBPCase of A. sativa as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After peptide mapping, the proteolytic cleavage patterns of the 63-kDa protein were also found to be different from those of the RuBPCase. Antibodies against SC-elements, RuBPCase, and the large subunit of RuBPCase were produced. Ouchterlony double immunodiffusion tests did not give crossreactions between the SC-elements and RuBPCase or the large subunit of this enzyme. Immunogold labelling of ultrathin sections showed that antibodies against the SC elements marked the stromacentre in Avena, but not the pyrenoids in Chlorella. Antibodies against the large subunit of RuBPCase, however, did not label the SC, but labelled the stroma of the plastids in Avena and the pyrenoids of Chlorella. In Opuntia, a comparable structure described as an SC was not labelled by any of the antisera. Immunoelectrophoretical investigations demonstrated a strong correlation between the presence of the 63-kDa protein and the occurrence of the SC in different Avena species with and without SC. PMID- 24225706 TI - Characterization of monoclonal antibodies to protoplast membranes of Nicotiana tabacum identified by an enzyme-linked immunosorbent assay. AB - Murine monoclonal antibodies to protoplast membrne antigens were generated using mouse myelomas and spleen cells from mice immunized with Nicotiana tabacum L. leaf protoplasts. For selecting antibody-secreting clones, a sensitive and rapid enzyme-linked immunosorbent assay (ELISA) for monoclonal antibody binding to immobilized cellular membrane preparations or immobilized protoplasts was developed. With intact protoplasts as immobilized antigen, the ELISA is selective for antibodies that bind to plasma-membrane epitopes present on the external surface of protoplasts. Using the membrane ELISA, a total of 24 hybridoma lines were identified that secreted antibodies to plant membrane epitopes. The protoplast ELISA and subsequent immunofluorescence studies identified four hybridoma lines as secreting antibodies which bound to the external surface of protoplasts and cells. The corresponding antigens were not species- or tissue specific, were periodatesensitive, and were located in membranes which equilibrated broadly throughout a linear sucrose gradient. When protein blots of electrophoretically separated membrane proteins were probed with these antibodies, a band of Mr 14 kilodaltons (kDa) and a smear of bands of Mr 45-120 kDa were labeled. An additional set of three antibodies appeared by immunofluorescence to bind to the plasma membrane of broken but not intact protoplasts and labeled membranes equilibrating at a density of approx. 1.12 kg.l(-1) in a linear sucrose density gradient. These classes of monoclonal antibodies enlarge the library of monoclonal antibodies (Norman et al. 1986, Planta 167, 452-459) available for the study of plant plasma-membrane structure and function. PMID- 24225707 TI - Water stress in Eucalyptus pauciflora: comparison of effects on stomatal conductance with effects on the mesophyll capacity for photosynthesis, and investigation of a possible involvement of photoinhibition. AB - Seedlings of Eucalyptus pauciflora Sieb. ex Spreng., grown in 4-1 pots, were stressed by withholding water while relationships between net assimilation rate (A) and intercellular partial pressure of CO2 (pi) in selected leaves were obtained repeatedly throughout the stress cycle. Water stress at first caused stomatal closure without any decline in the A(pi) relationship. As stress became more severe, the A(pi) relationship was affected as well. This always affected assimilation rate at both high and low intercellular partial pressures of CO2. It was then tested whether water-stressed leaves were more prone to photoinhibition than unstressed ones. Plants were water-stressed while at the same time subjected to strong photon flux area density (2000 MUmol quanta.m(-2).s(-1)). A possible light-induced inhibition was assessed by comparing quantum yields of photosynthesis with light directed onto one or the other surface of the leaf. A decline in quantum yield was observed, and the decline on the previously irradiated side was more pronounced than on the previously shaded side, but the effect was small and disappeared entirely within 1 d of rewatering the plants. It is concluded that photoinhibition can play a role, but not an important one, in the effect of water stress on the A(pi) relationship in leaves of E. pauciflora. PMID- 24225708 TI - Sucrose uptake in isolated phloem of celery is a single saturable transport system. AB - The uptake of different sugars was studied in segments of isolated phloem from petioles of celery (Apium graveolens L.) in order to determine the kinetics and specificity of phloem loading in this highly uniform conductive tissue. The uptake kinetics of sucrose and the sugar alcohol, mannitol, which are both phloem translocated, indicated presence of a single saturable system, while uptake of non-phloem sugars (glucose and 3-O-methylglucose) exhibited biphasic kinetics with lower uptake rates than those for sucrose and mannitol. The presence of unlabeled mannitol, 3-O-methylglucose and maltose in the incubation solution did not cause inhibition of labeled-sucrose uptake, indicating high carrier specificity and lack of sucrose hydrolysis in vivo. The pH optimum for sucrose uptake was 5-6. Furthermore, a rapid and transient alkalinization of the external media by sucrose indicated a sugar/H(+)-cotransport mechanism. Dual-labeling experiments showed that sucrose influx continued at a constant rate (V max=15 MUmol.h(-1).(g FW)(-1)), whereas sucrose efflux was low and insensitive to external concentration. Therefore, the saturable uptake kinetics for sucrose did not appear to be the result of an equilibrium between rates of sucrose influx and efflux. PMID- 24225709 TI - Purification of an autocatalytic protein-glycosylating enzyme from cell suspensions of Daucus carota L. AB - A glycosyltransferase was identified in the 174 000 . g membrane pellet and the supernatant from extracts of cell suspensions of Daucus carota L. The enzyme from the supernatant was enriched 475-fold, and sodium dodecyl sulfate-gel electrophoresis and fluorography of this purified sample showed that the only enriched protein band (40 000 Da) was simultaneously an enzyme and a glucose acceptor. Gel filtration and electrophoresis under non-denaturing conditions proved that in vivo this protein provides the subunits for a very large molecule. Radio-gas-liquid chromatography demonstrated that only one glucosyl moiety was transferred from UDP-glucose to the protein. PMID- 24225710 TI - Acetyl-CoA-carboxylase activity in normally developing wheat leaves. AB - In order to investigate the role of acetyl CoA carboxylase (ACC) in the regulation of fatty-acid biosynthesis in chloroplasts, the activities and relative amounts of the enzyme have been measured in the tissue of wheat (Triticum aestivum L.) leaves undergoing development and cellular differentiation. The total activity in the first leaves of 5- to 7-d-old plants was similar but decreased to less than half in 9-d-old plants. The activity of ACC in the cells of the first leaf of 7-d-old plants doubled when cell age increased from 24 to 48 h, remained relatively constant for a further 24 h and then declined. The amount of ACC in cells increased 15-fold during the first 36 h of cell enlargement. Cells more than 36 h old contained about two-thirds the maximum amount of ACC found in younger cells. The most rapid phase of fatty-acyl accumulation in lipids was in cells aged between 60 and 84 h. Tenfold changes in the activity of ACC were observed when the assay conditions with respect to ATP, ADP, Mg(2+) and pH were changed to correspond to the physiological conditions in chloroplasts during light/dark transitions. This observation and the magnitude of the changes in the optimum activity and amount of ACC in leaf cells undergoing development are consistent with a role for ACC in the regulation of the flow of carbon from acetyl CoA to fatty acids in chloroplasts. PMID- 24225711 TI - Ammonium regulation of urate uptake in Chlamydomonas reinhardtii. AB - Urate was taken up at a negligible rate by Chlamydomonas reinhardtii cells grown on ammonium and transferred to media containing urate plus ammonium or urate plus chloral hydrate or cycloheximide. Addition of ammonium to cells actively consuming urate produced a rapid inhibition of urate uptake whereas the intracellular oxidation of urate was unaffected. Methylammonium but not glutamine or glutamate inhibited urate uptake. Addition of L-methionine-DL-sulfoximine to cells actively consuming urate provoked ammonium excretion, which was accompanied by a rapid inhibition of urate uptake. In cells growing on urate and exhibiting noticeable levels of nitrite-reductase activity, nitrite caused a sudden inhibition of urate uptake whereas nitrate required a time to induce nitrate reductase and to exert its inhibitory effect on uptake. The urate-uptake system did not require urate for induction since the urate-uptake capacity appeared in nitrogen-starved cells. From these results it is concluded that, in Chlamydomonas reinhardtii, ammonium inhibits urate uptake and also acts as co-repressor of the uptake system. PMID- 24225712 TI - Auxin carriers in Cucurbita vesicles : I. Imposed perturbations of transmembrane pH and electrical potential gradients characterised by radioactive probes. AB - The behaviour of radioactive probes of transmembrane pH gradients ([(14)C]butyric acid) and electrical potential gradients ((86)Rb(+) and S(14)CN(-)) has been characterised in membrane vesicles from Cucurbita pepo L. hypocotyls subjected to changing gradients and ionophore-mediated changes in the conductivity of K(+) and H(+) ions. The vesicles are sealed in the presence of 25 mM KCl. The K(+) ionophore valinomycin changes the distribution of (86)Rb(+) and of S(14)CN(-) in opposite directions, which depend on the external K(+) concentration. The accumulation of [(14)C]butyric acid by the vesicles and its association with the membranous phase are enhanced by increasing acidity, as expected for this lipophilic weak acid (pKa=4.8). Uptake of S(14)CN(-) increases and valinomycin stimulated (86)Rb(+) uptake decreases when the external pH is lowered, indicating a strongly pH-dependent H(+) diffusion potential. PMID- 24225713 TI - Auxin carriers in Cucurbita vesicles : II. Evidence that carrier-mediated routes of both indole-3-acetic acid influx and efflux are electroimpelled. AB - The association at 0 degrees C of [(3)H]indole-3-acetic acid (IAA) with membrane vesicles prepared from Cucurbita pepo L. hypocotyls at pH 7.9 and resuspended at pH 6.0 was greatly diminished by osmotic shrinkage. Nonradioactive IAA inhibited a large proportion of this association thus revealing a saturable component, also decreased by osmotic shrinkage, which mainly represents operation of an auxin uptake carrier, with saturable binding having only a minor role. The contribution of this carrier to the steady state of IAA transport changed in the same direction as the proton motive force (transmembrane pH and electrical potential difference) which was manipulated using the K(+) ionophore valinomycin with differing K(+) concentration gradients over a range of assay pH values. We conclude that the uptake carrier is electroimpelled with IAA(-)/2H(+) (or IAAH/H(+)) symport as a possible mechanism. The same procedures were used to examine the behaviour of the IAA efflux carrier, whose inhibition by N-1 naphthylphthalamic acid (NPA) causes an increase in IAA accumulation by the vesicles. The extent of NPA-stimulation was linked to the magnitude of the electrical potential difference (negative inside) across the vesicle membranes. We conclude that IAA transport by the efflux carrier is electroimpelled, with IAA(-) a likely substrate. PMID- 24225714 TI - Auxin carriers in Cucurbita vesicles : III. Specificity, with particular reference to 1-naphthylacetic acid. AB - Carrier-mediated uptake of indole-3-acetic acid (IAA) by microsomal vesicles from Cucurbita pepo L. hypocotyls was strongly inhibited by 2,4-dichlorophenoxyacetic acid (2,4-D; i 50= 0.3 MUM) but only weakly by 1-naphthylacetic acid (NAA). The fully ionised auxin indol-3-yl methanesulphonic acid also inhibited (i 50=3 MUM). The same affinity ranking of these auxins for the uptake carrier, an electroimpelled auxin anion-H(+) symport, is demonstrable in hypocotyl segments. The specificity of the auxin-anion eflux carrier was tested by the ability of different nonradioactive auxins to compete with [(3)H]IAA and reduce the stimulation of net radioactive uptake by N-1-naphthylphthalamic acid (NPA), a noncompetitive inhibitor of this carrier. By this criterion, NAA and IAA had comparable affinities, with 2,4-D interaction more weakly. Stimulation of [(3)H]IAA uptake by NAA, as a result of competition for the efflux carrier, could also be demonstrated when a suitable concentration of 2,4-D was used selectively to inhibit the uptake carrier. However, when [(3)H]NAA was used, no stimulation of its association with vesicles by NPA, 2,3,5-triiodobenzoic acid, or nonradioactive NAA was found. In hypocotyl segments, [(3)H]NAA net uptake was much less sensitive to NPA stimulation than was [(14)C]IAA uptake. The apparent contradictions concerning NAA could be explained by carrier-mediated auxin efflux making a smaller relative contribution to the overall transport of NAA than of IAA. The relationship between carrier specificity as manifested in vitro and the specificity of polar auxin transport is discussed. PMID- 24225715 TI - Differential induction of enzyme in soybean cell cultures by elicitor or osmotic stress. AB - Soybean cell cultures were challenged either by glucan elicitor from Phytophthora megasperma f.sp. glycinea or by osmotic stress (0.4 M glucose). Osmotic stress induced production of a microsomal NADPH-dependent flavone synthase (flavone synthase II) which catalyses conversion of (2S)-naringenin to apigenin. In one of our cell-lines this enzyme activity was not detected either in unchallenged cells or in cells treated with glucan elicitor. Inducibility of flavone synthase II by 0.4 M glucose was highest at the end of the linear growth phase. Changes in the activities of a number of other enzymes were determined after treatment of the cells with elicitor or 0.4 M glucose. The activities of phenylalanine ammonialyase, cinnamate 4-hydroxylase, chalcone synthase and dihydroxypterocarpan 6a-hydroxylase all increased with elicitor and with osmoticum, albeit to a different degree. The rise in enzyme activity occurred later with osmoticum than with elicitor. The prenyltransferase involved in glyceollin synthesis was induced strongly by elicitor but only very weakly by osmoticum, whereas isoflavone synthase and NADPH: cytochrome-c reductase were only induced by elicitor. The activity of glucose-6-phosphate dehydrogenase did not change with elicitor or with osmoticum. Different product patterns were also obtained: whereas with elicitor, glyceollin I was the major product, intermediates of the glyceollin pathway (7,4'-dihydroxyflavanone, trihydroxypterocarpan) accumulated with osmoticum. PMID- 24225716 TI - Gibberellins regulate seed germination in tomato by endosperm weakening: a study with gibberellin-deficient mutants. AB - The germination of seeds of tomato [Lycopersicon esculentum (L.) Mill.] cv. Moneymaker has been compared with that of seeds of the gibberellin-deficient dwarf-mutant line ga-1, induced in the same genetic background. Germination of tomato seeds was absolutely dependent on the presence of either endogenous or exogenous gibberellins (GAs). Gibberellin A4+7 was 1000-fold more active than commercial gibberellic acid in inducing germination of the ga-1 seeds. Red light, a preincubation at 2 degrees C, and ethylene did not stimulate germination of ga 1 seeds in the absence of GA4+7; however, fusicoccin did stimulate germination independently. Removal of the endosperm and testa layers opposite the radicle tip caused germination of ga-1 seeds in water. The seedlings and plants that develop from the detipped ga-1 seeds exhibited the extreme dwarfy phenotype that is normal to this genotype. Measurements of the mechanical resistance of the surrounding layers showed that the major action of GAs was directed to the weakening of the endosperm cells around the radicle tip. In wild-type seeds this weakening occurred in water before radicle protrusion. In ga-1 seeds a similar event was dependent on GA4+7, while fusicoccin also had some activity. Simultaneous incubation of de-embryonated endosperms and isolated axes showed that wild-type embryos contain and endosperm-weakening factor that is absent in ga-1 axes and is probably a GA. Thus, an endogenous GA facilitates germination in tomato seeds by weakening the mechanical restraint of the endosperm cells to permit radicle protrusion. PMID- 24225717 TI - Nitrogen limitation and amino-acid metabolism of Chlorella symbiotic with green hydra. AB - Chlorella algae symbiotic in the digestive cells of Hydra viridissima Pallas (green hydra) were found to contain less amino-N and smaller pools of free amino acids than their cultured counterparts, indicating that growth in symbiosis was nitrogen-limiting. This difference was reflected in uptake of amino acids and subsequent incorporation into protein; symbiotic algae incorporated a greater proportion of sequestered radioactivity, supplied as (14)C-labelled alanine, glycine or arginine, than algae from nitrogen-sufficient culture, presumably because smaller internal pools diluted sequestered amino acids to a lesser extent. Further experiments with symbiotic algae showed that metabolism of the neutral amino acid alanine differed from that of the basic amino acid arginine. Alanine but not arginine continued to be incorporated into protein after uptake ceased, and while internal pools of alanine were exchangeable with alanine in the medium, those of arginine were not exchangeable with external arginine. Thin layer chromatography of ethanol-soluble extracts of algae incubated with [(14)C]alanine or [(14)C]arginine showed that both were precursors of other amino acids. The significance of nitrogen-limiting growth of symbiotic algae is discussed in terms of host-cell regulation of algal cell growth and division. PMID- 24225718 TI - Initiation of auxin autonomy in Nicotiana glutinosa cells by the cytokinin biosynthesis gene from Agrobacterium tumefaciens. AB - Agrobacteria carrying mutations at the auxin-biosynthesizing loci (iaaH and iaaM of the Ti plasmid) induce shoot-forming tumors on many plant species. In some cases, e.g. Nicotiana glutinosa L., tumors induced by such mutant strains exhibit an unorganized and fully autonomous phenotype. These characteristics are stable in culture at both the tissue and cellular level. We demonstrate that the cytokinin-biosynthesis gene (ipt) of the Ti plasmid is responsble for the induction of both auxin and cytokinin autonomy in N. glutinosa. Cloned cell lines carrying an ipt gene but lacking iaaH and iaaM are capable of accumulating indole 3-acetic acid. Interestingly, non-transformed N. glutinosa tissues exhibit an auxin-requiring phenotype when they are grown on medium supplemented with an exogenous supply of cytokinin. These results strongly indicate that exogenously supplied cytokinin does not mimic all the effects of the expression of the ipt gene in causing the auxin-autonomous growth of N. glutinosa cells. PMID- 24225719 TI - The photosynthetic induction response in wheat leaves: net CO2 uptake, enzyme activation, and leaf metabolites. AB - The photosynthetic induction response was studied in whole leaves of wheat (Triticum aestivum L.) following 5-min, 30-min and 10-h dark periods. After the 5 min dark treatment there was a rapid burst in the rate of photosynthesis upon illumination (half of maximum after 30s), followed by a slight decrease after 1.5 more min and then a gradual rise to the maximum rate. During this initial burst in photosynthesis, there was a rapid rise in the level of 3-phosphoglycerate (PGA) and a high PGA/triose-phosphate (triose-P) ratio was obtained. In addition, after the 5-min dark treatment, ribulose-1,5-bisphosphate carboxylase (Rubisco, EC 4.1.1.39), ribulose-5-phosphate kinase (EC 2.7.1.19) and chloroplastic fructose-1,6-bisphosphatase (EC 3.1.3.11) maintained a relatively high state of activation, and maximum activation occurred within 1 min of illumination. The results indicate there is a high capacity for CO2 fixation in the cycle upon illumination but attaining maximum rates requires an increase in the ribulose-1,5 bisphosphate (RuBP) pool (adjustment in triose-P utilization for carbohydrate synthesis versus RuBP synthesis). With both the 30-min and 10-h dark pretreatments there was only a slight rise in photosynthesis upon illumination, followed by a lag, then a gradual increase to steady-state (half-maximum rate after 6 min). In contrast to the 5-min dark treatment, the level of PGA was low and actually decreased initially, whereas the level of RuBP increased and was high during induction, indicating that Rubisco is limiting. This regulation via the carboxylase was not reflected in the initial extractable activity, which reached a maximum by 1 min after illumination. The light activation of chloroplastic fructose-1,6-bisphosphatase in leaves darkened for 30 min and 10 h prior to illumination was relatively slow (reaching a maximum after 8 min). However, this was not considered to limit carbon flux through the carbon-fixation cycle during induction since RuBP was not limiting. When photosynthesis approached the maximum steady-state rate, a high PGA/triose-P ratio and a high PGA/RuBP ratio were obtained. This may allow a high rate of photosynthesis by producing a favorable mass-action ratio for the reductive phase (the conversion of PGA to triose phosphate) while stimulating starch and sucrose synthesis. PMID- 24225720 TI - Comparison of de-novo flower-bud formation in a photoperiodic and a day-neutral tobacco. AB - Regeneration of flower buds in thin tissue layers from pedicels of photoinduced short-day (SD) tobacco, Nicotiana tabacum L. cv. Maryland Mammoth, is described. Up to seven flower buds per explant were obtained in a medium containing Murashige and Skoog's macro- and microclements, 100 mg/l myoinositol, 0.1 mg/l thiamine-HCl, 6% glucose, 5 MUM N(6)-benzylaminopurine, and 0.5 MUM alpha naphthaleneacetic acid. Usually some vegetative buds were also formed in the pedicel thin tissue layers. Thin tissue layers from other positions in the induced SD tobacco regenerated vegetative buds only. A comparative study with a day-neutral (DN) tobacco, Samsun, showed that the capacity to form de-novo flower buds was more localized and less strongly determined in photoperiodic than in the DN tobacco. The differences between the photoperiodic and DN tobaccos in flower bud regeneration capacity are thus quantitative and not qualitative. The basis for this quantitative difference is not known, but may depend on factors controlling production of floral stimulus (florigen) and competency of cells to respond to florigen, and-or stability of the determined state to form flower buds in vitro. PMID- 24225721 TI - Spinach ferredoxin is a calcium-binding protein. AB - Spinach-leaf ferredoxin was identified as a calcium-binding protein by (45)Ca autoradiography on nitrocellulose membranes and with the cationic carbocyanine dye 1-ethyl-2-[3-(1-ethylnaphtho[1,2-d]thiazolin-2-ylidene)-2-methylpropenyl] naphtho[1,2-d]thiazolium bromide ("stains-all"). Binding of (45)Ca was observed at pH 6.8 and pH 7.8 and in the presence of 5 mM and 20 mM MgCl2. At the higher MgCl2 concentration the Ca(2+)-binding capacity is reduced. Only micromolar concentrations of LaCl3, however, are required to achieve a similar effect. Both the oxidized and reduced forms of ferredoxin bind calcium. PMID- 24225722 TI - Doped organic transistors operating in the inversion and depletion regime. AB - The inversion field-effect transistor is the basic device of modern microelectronics and is nowadays used more than a billion times on every state-of the-art computer chip. In the future, this rigid technology will be complemented by flexible electronics produced at extremely low cost. Organic field-effect transistors have the potential to be the basic device for flexible electronics, but still need much improvement. In particular, despite more than 20 years of research, organic inversion mode transistors have not been reported so far. Here we discuss the first realization of organic inversion transistors and the optimization of organic depletion transistors by our organic doping technology. We show that the transistor parameters--in particular, the threshold voltage and the ON/OFF ratio--can be controlled by the doping concentration and the thickness of the transistor channel. Injection of minority carriers into the doped transistor channel is achieved by doped contacts, which allows forming an inversion layer. PMID- 24225723 TI - Air pollution exposures during adulthood and risk of endometriosis in the Nurses' Health Study II. AB - BACKGROUND: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis. OBJECTIVE: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter<2.5 MUm, between 2.5 and 10 MUm, and <10 MUm, (PM2.5, PM10-2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses' Health Study II. METHODS: Proximity to major roadways and outdoor levels of PM2.5, PM10-2.5, and PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk. RESULTS: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM2.5, PM10-2.5, or PM10 averaged over follow-up or during the previous 2- or 4-year period. CONCLUSIONS: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women. PMID- 24225725 TI - Robotic assisted prostatic surgery in the Trendelenburg position does not impair cerebral oxygenation measured using two different monitors: A clinical observational study. AB - BACKGROUND: Robotic assisted prostatic surgery is frequently used because of its reduced side-effects compared with conventional surgery. During surgery, an extreme Trendelenburg position and CO2 pneumoperitoneum are necessary, which may lead to cerebral oedema, can potentially reduce brain perfusion and therefore could impair cerebral oxygenation. Cerebral oxygen saturation can be measured non invasively using near-infrared spectroscopy (NIRS). OBJECTIVE: The hypothesis of the present study was that steep Trendelenburg positioning during robotic assisted prostatic surgery impairs cerebral oxygen saturation measured using two different NIRS monitors. DESIGN: Clinical observational study. SETTING: Primary care university hospital, study period from March 2012 to February 2013. PATIENTS: A total of 29 patients scheduled for robotic assisted prostatic surgery in a steep Trendelenburg position. INTERVENTIONS: Cerebral oxygen saturation was measured throughout anaesthesia using the INVOS sensor (a trend monitor using two infrared wavelengths) for one hemisphere and the FORE-SIGHT sensor (a monitor using four wavelengths of laser light to calculate absolute oxygen saturation) for the other hemisphere in an alternate randomisation. MAIN OUTCOME MEASURE: Changes in cerebral oxygenation of more than 5% during surgery in the Trendelenburg position. RESULTS: The median duration of Trendelenburg positioning was 190 (interquartile range 130 to 230) min. Cerebral oxygen saturation decreased with INVOS from 74 +/- 5% at baseline to a lowest value of 70 +/- 4% with a slope of -0.0129 min(-1) (P < 0.01) and with FORE-SIGHT from 72 +/- 5% at baseline to a nadir of 70 +/- 3% with a slope of -0.008 min(-1) (P < 0.01). Comparing INVOS with FORE-SIGHT, there was a good association, with a slope of 0.86 +/- 0.04 (P < 0.01). CONCLUSION: Both monitors showed a clinically irrelevant decrease in cerebral oxygen saturation of less than 5% over 4 h in a steep Trendelenburg position combined with CO2 pneumoperitoneum in patients undergoing robotic assisted prostatic surgery. This extreme positioning seems to be acceptable with regard to cerebral oxygenation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ID NCT01275898. PMID- 24225726 TI - Pain assessment in the postanaesthesia care unit using pupillometry: A cross sectional study after standard anaesthetic care. AB - BACKGROUND: Patients assess their own pain with a numerical rating scale (NRS). In the postanaesthesia care unit (PACU), NRS helps to determine and monitor analgesic administration, but is useless in patients who are unable to communicate. In non-PACU patients, acute pain increases pupillary diameter and pupillary light reflex amplitude (PLRA), the difference between pupillary diameter before and after light stimulation. OBJECTIVES: To study the association between postoperative pain (NRS) and pupillary diameter or PLRA in PACU patients after routine anaesthetic care. DESIGN: Cross-sectional cohort study. SETTING: Bichat-Claude Bernard Hospital, Paris. PATIENTS: One hundred and forty-five patients undergoing planned surgery under general anaesthesia. INTERVENTIONS: NRS, pupillary diameter and PLRA were measured on arrival in the PACU. When NRS was more than 4, intravenous morphine titration was started and a second measurement performed. MAIN OUTCOME MEASURES: Association between NRS and pupillary diameter or PLRA was assessed with Pearson correlation coefficient (r) as was association between changes in these variables after morphine titration. RESULTS: Mean NRS was 4.7, and was more than 4 in 79 patients (55%). No statistically significant association was observed between NRS and pupillary diameter (r = 0.10, P = 0.54) or PLRA (r = 0.03, P = 0.72). Twenty-seven patients (19%) received morphine titration with significant decreases in NRS, pupillary diameter and PLRA afterwards. No association was observed between NRS changes and pupillary diameter or PLRA changes. CONCLUSION: Acute postoperative pain is not associated with pupillary diameter or PLRA. Further research is required to develop tools to assess pain in the PACU. PMID- 24225727 TI - Iowa Satisfaction with Anesthesia Scale for general anaesthesia. PMID- 24225728 TI - History of anaesthesia: early forms of local anaesthesia. AB - The direct application of volatile anaesthetic and the application of intense cold to traumatic injuries and surgical sites were important steps in 18th and 19th century anaesthesia. Local tissue temperature could be brought down by the application of ice and salt by the surgeon. Techniques used topical applications of chloroform, Dutch Oil, amyl hydrate, the vaporisation of nebulised ether, methylene and ethylene chloride applied by spray or fumigation and vaginal douche with carbonic acid gas. Mastering the projection of cold was extremely difficult. Keeping the aperture of the device used for the spraying of anaesthetic liquids clear of obstruction became a major challenge for instrument makers. To improve the precision of the jet, a different system of nozzles had to be invented. Nineteenth century medical practitioners were able to call on general anaesthesia, but some individuals and specific indications such as minor surgery called for an alternative approach. The introduction of cocaine in 1884 completely changed common practice. PMID- 24225729 TI - Reply to: A Simple epidural simulator: fruits and potatoes, and what kind of bananas? PMID- 24225732 TI - A complex odontoma of the anterior maxilla associated with an erupting canine. AB - Many developmental anomalies of the jaw are accidentally diagnosed during radiographic investigations for other symptoms. Complex odontomas are odontogenic tumours, relatively rare in the anterior maxilla and generally asymptomatic. Frequently the odontoma may interfere with the eruption of teeth. This paper describes a case of complex odontoma in an 8-year-old girl, which resulted in the palatal displacement of the lateral incisor and an erupting permanent canine. A calcified mass was seen on the radiograph and was provisionally diagnosed as an odontoma which was surgically enucleated. Routine follow-up was carried out for more than 1 year and no recurrence was seen. PMID- 24225730 TI - Penicillinolide A: a new anti-inflammatory metabolite from the marine fungus Penicillium sp. SF-5292. AB - In the course of studies on bioactive metabolites from marine fungi, a new 10 membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher's method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-alpha, IL-1beta and IL-6 production, and these anti inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IkappaB-alpha, NF-kappaB nuclear translocation, and NF-kappaB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro inflammatory mediators and NF-kappaB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation. PMID- 24225733 TI - Rectosigmoid gallstone coleus: a rare emergency presentation. AB - An elderly woman presented with abdominal pain and vomiting, was known to have gallstones. A CT scan was arranged identifying gallstone ileus and cholecystitis. Ensuing sepsis precipitated fast atrial fibrillation delaying the planned laparotomy. Her symptoms subsequently resolved with conservative management. Ten days following admission her abdomen became distended. A repeat CT scan showed large bowel dilation with intramural air suggestive of obstruction and bowel ischaemia. Emergency laparotomy was performed identifying a large 23 mm gallstone impacted at the rectosigmoid junction (gallstone coleus). The stone was milked back to the transverse colon where it was retrieved and a transverse loop colostomy was formed. Gallstone ileus is rare; gallstone coleus is even rarer. On review of the published literature both entities have not been seen in the same patient during the same admission or indeed caused by the same gallstone. PMID- 24225734 TI - Transient intussusception: rare cause of abdominal pain in cystic fibrosis. PMID- 24225735 TI - Successful revision of polyethylene only, after delayed presentation of a dislocated bearing in an Oxford unicompartmental knee replacement. AB - We present the case of a 79-year-old man who dislocated the mobile bearing of a well-functioning Oxford unicompartmental knee replacement in a fall. The diagnosis was delayed by 14 days during which time the patient remained fully mobile. At the time of arthrotomy, there was some visible burnishing of the femoral articular surface where it had been rubbing on the tibial component. Both components were soundly fixed and had been functioning well for 7 years. The decision was made to leave the components in situ and simply replace the mobile meniscal bearing. The patient returned to full normal activity and has been followed-up for 3.5 years. Serial X-rays reveal no evidence of polyethylene wear and the knee remains pain free and fully functional. We conclude that it is safe to retain the components of an Oxford unicompartmental knee replacement despite some evidence of surface damage. Replacing just the mobile meniscus gave a good result in our patient. PMID- 24225736 TI - Under pressure: a contribution to the pathogenesis of acquired ileal atresia. AB - An acquired ileal atresia is a rare occurrence. A 3-week-old neonate is presented, who developed postnatally a type 2 ileal atresia and an ileal stenosis within a pre-existing internal hernia secondary to an adhesion band. The literature reports a total of eight cases (4 females) with acquired ileal atresia in babies ranging in age from 3 weeks to 2 years (median 4 months). Mechanical forces (eg, adhesion band, intussusception and volvulus) onto the intestine are most frequently (75%) implicated as the primary event. The distal ileum is most often affected and a type 3A atresia is identified in six of eight (75%) cases. PMID- 24225737 TI - A patient with pneumopericardium secondary to extranodal T-cell lymphoma. AB - Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoma derived from either activated NK cells or cytotoxic T cells. Most cases with T/NK cell lymphoma present with extranodal manifestations. Primary nodal disease is very rare. The upper respiratory tract is the most common site involved in extranodal disease. Symptoms include epistaxis and nasal obstruction. T/NK cell lymphomas show aggressive and invasive clinical progression, with a poor prognosis. Without treatment, survival is measured in months. We report a case of a 51-year-old male patient with pneumopericardium as a complication of intestinal T/NK cell lymphoma. To the best of our knowledge, this is the first report showing pneumopericardium as a fatal complication of T/NK cell lymphoma. Pneumopericardium should be considered in patients diagnosed with T/NK cell lymphoma presenting with chest pain. PMID- 24225738 TI - Formation of alumina nanocapsules by high-energy-electron irradiation of Na dawsonite nanorods. AB - We report the synthesis of unique Al2O3 nanocapsules by high-energy-electron irradiation of Na-dawsonite and a formation mechanism different from thermal decomposition which usually produces NaAlO2. The novel decomposition process may open up a shortcut for fabricating hollow nanostructures. PMID- 24225739 TI - Sometimes consensus and expert opinion is the best we can do. PMID- 24225740 TI - Effects of antioxidant supplementation on exercise performance in acute normobaric hypoxia. AB - BACKGROUND/OBJECTIVES: To compare the effects of a 3-week supplementation between two different mixtures of antioxidants and placebo on aerobic exercise performance in acute normobaric hypoxia. SUBJECTS/METHODS: Seventeen subjects were randomly assigned in a double-blind fashion to receive a broad-based antioxidants supplement containing beta-carotene, ascorbic acid, d-alpha tocopherol-succinate, N-acetylcysteine, riboflavin, zinc, and selenium (antioxidant capsule group [AO group]), or a combination of alpha-ketoglutaric acid (alpha-KG) and 5-hydroxymethylfurfural (5-HMF; CYL concentrate supplementation group [CS group]), or placebo (PL group). Before and after supplementation, subjects performed two incremental cycle-exercise tests until exhaustion. The first test was conducted under normoxic conditions (LA, FiO2 of 20.9%, ~547 m) and the second after the 3-week supplementation period under normobaric hypoxic conditions (AHA, FiO2 of 12.9%, ~4300m). RESULTS: In CS peak cycling performance (peak power) declined from LA to AHA 7.3% (90% CI: 2.2-12.4) less compared with PL (p = .04) and 6.7% (90%CI: 3.2-10.2) less compared with AO (p = .03). Better maintenance of aerobic exercise capacity in CS was associated with an attenuated reduction in maximal heart rate in hypoxia. CONCLUSIONS: Aerobic exercise performance was less impaired in acute normobaric hypoxia after 3 weeks with supplementation of alpha-KG and 5-HMF compared with a broad-based antioxidants supplement or PL. PMID- 24225741 TI - The use and value of polling to determine public opinion on GMOs in Europe: limitations and ways forward. AB - In this article, we review and assess existing surveys that attempt to gauge public opinion about GM crops. This review shows that consumer surveys can be something of a blunt instrument. Questionnaires, however well-constructed and professionally delivered, are answered in a vacuum of knowledge and elicit misleading responses. People recurrently admit they lack information on the technology behind GM food. It is a part of the general unfamiliarity with the food production process with which people show equal, if not greater, concern. Lacking control over a process involving such an emotive subject like food makes people uneasy and reluctant to accept "unknowns". In addition, if people give answers to hypothetical questions, they do so as "cautious citizens" rather than consumers and this is not a good guide to actual behavior in real life. Qualitative studies using focus groups can be a much better guide to how people really feel about issues, but they also need expert facilitation and analysis to be of real value. An even better guide to acceptance and purchasing behavior (if that is the objective) is to put people in a situation where they are actually making a choice of whether or not to buy GM products. PMID- 24225742 TI - The predictive ability of a CK5/p63/CK8/18 antibody cocktail in stratifying breast papillary lesions on needle biopsy: an algorithmic approach works best. AB - OBJECTIVES: Immunohistochemical markers have been shown to assist in the stratification of breast papillary lesions. We evaluated the ability of different cytokeratin (CK) and p63 expression profiles on needle biopsy specimens to predict excision diagnoses. METHODS: A CK5/p63/CK8/18 antibody cocktail was applied to 58 needle biopsy specimens (32 papillomas, 7 atypical papillomas, 19 papillary carcinomas on excision). RESULTS: p63 expression was greater in papillomas than in atypical papillomas (P = .044) and papillary carcinomas (P< .0001). Papillary carcinomas and atypical papillomas showed greater CK8/18 expression (and conversely less CK5 expression) than did papillomas (P < .0001). Negative or focal p63 expression was 96% sensitive for diagnosing any atypical lesion (atypical papilloma or papillary carcinoma) on excision, whereas CK8/18 predominant expression (>=80% cells) was 100% sensitive. In contrast, the sensitivity of the original diagnosis was only 81%. The greatest accuracy for the diagnosis of atypical papillary lesions (95%) was achieved when both p63 and cytokeratins were used in combination in an algorithmic fashion. This method also correctly identified all cases that had papillary carcinoma (100% sensitivity) on excision. CONCLUSIONS: Although a single stain or combination cannot independently stratify papillary lesions, a CK5/p63/CK8/18 antibody cocktail is a useful adjunct to morphology for evaluating breast papillary lesions in needle biopsy specimens. PMID- 24225743 TI - Comparison of outcomes of group O vs non-group O premature neonates receiving group O RBC transfusions. AB - OBJECTIVES: At some institutions all infants requiring RBC transfusions in neonatal intensive care units (NICUs) receive only group O RBCs. Although transfused group O plasma is minimized in packed RBCs, small amounts of residual anti-A, anti-B, and anti-A,B in group O packed RBCs may bind to the corresponding A and B antigens of non-group O RBCs, possibly hemolyzing their native RBCs and thereby releasing free hemoglobin, theoretically resulting in hypercoagulability and promoting bacterial growth from free iron. METHODS: Premature infants in the University of Kentucky Children's Hospital NICU database who were transfused (all received group O transfusions) were compared for a number of severity markers to determine if non-group O patients had worse outcomes than group O patients. RESULTS: In this NICU sample, 724 neonates received at least 1 blood component. No significant differences were found between group O and non-group O infants with regard to final disposition or complications. CONCLUSIONS: This reassuring finding validates the longstanding neonatal transfusion practice of using group O packed RBCs for infants of all blood groups in the NICU. However, a recent study shows increased mortality from necrotizing enterocolitis in group AB neonates at a facility transfusing only group O RBCs to neonates of all blood groups and suggests a change in neonatal transfusion practice to ABO group-specific RBCs; therefore more studies may be warranted. PMID- 24225744 TI - Splenic lymphoid subsets with less well-recognized phenotypes mimic aberrant antigen expression. AB - OBJECTIVES: Flow cytometry can assist in the diagnosis of lymphoma by identifying aberrant antigen expression. Recognition of aberrancy requires knowledge of the phenotype of normal lymphoid cells. METHODS: Lymphoid subsets were characterized in 20 spleens removed for traumatic rupture, using 8-color flow cytometry. RESULTS: Normal variation in splenic lymphoid subsets was highlighted and several well-recognized subsets were identified: CD5+ B cells (20/20 specimens), CD7- T cells (20/20), and CD3 brightgammadeltaT cells (16/20). In addition, less well recognized lymphoid subsets that resemble those described in lymphoma were identified in all specimens: CD5- T cells (4.5 +/- 5.1% of T cells), CD2- natural killer (NK) cells (38 +/- 7% of NK cells), and CD7dim+ NK cells. Similar populations were identified in 20 control peripheral blood specimens, where they represented a smaller proportion of total lymphoid cells. CONCLUSIONS: Familiarity with the phenotype of normal lymphoid subsets can help prevent misinterpreting flow cytometric data. Furthermore, in the context of neoplastic cells, the phenotype may suggest expanded normal subsets rather than aberrant antigen expression. PMID- 24225745 TI - Polyclonal antibody targeting SOX11 cannot differentiate mantle cell lymphoma from B-cell non-Hodgkin lymphomas. AB - OBJECTIVES: To determine whether SOX11 is a diagnostic marker of mantle cell lymphoma (MCL). METHODS: We analyzed SOX11 expression in 349 B-cell non-Hodgkin lymphomas (B-NHLs) via immunohistochemistry. RESULTS: Nuclear staining of SOX11 was observed in 54 (93.1%) of 58 MCLs. We noticed that SOX11 protein was also expressed on the nuclei in 8 (21.6%) of 37 B-lymphoblastic lymphomas, 45 (32.6%) of 138 diffuse large B-cell lymphomas, 15 (44.1%) of 34 follicular lymphomas, 8 (30.8%) of 26 Burkitt lymphomas, 2 (10.0%) of 20 chronic lymphocytic leukemia/small cell lymphomas, and 3 (18.8%) of 16 marginal zone lymphomas. CONCLUSIONS: Although the positive rate of SOX11 expression in MCL was significantly higher than other B-NHLs (P < .001), polyclonal antibody targeting SOX11 is not able to identify MCL from B-NHLs because the nuclear staining of SOX11 was widely positive in B-NHLs. PMID- 24225746 TI - An intervention to improve the timing of vancomycin levels. AB - OBJECTIVES: Blood samples for vancomycin levels are often drawn too early, leading to potential misinterpretation of results. However, only a few studies describe interventions to reduce mistimed vancomycin levels. METHODS: We implemented an information technology (IT)-based intervention that provided educational instructions to nurses and determined the percentage of levels drawn too early for 27 months before (n = 6,291) and 14 months after (n = 3,608) the intervention. In addition, we conducted nurse interviews (n = 40) and dataset analysis to assess the root causes of mistimed levels. RESULTS: The percentage of vancomycin timing errors decreased from 39% (2,438/6,291) to 32% (1,137/3,608), though in a time series analysis this decrease was not statistically significant (P = .64). Four common causes of mistimed levels were found: (1) unclear provider orders, (2) scheduling levels to be drawn with morning laboratory tests, (3) lack of communication between providers, and (4) failure to adjust the blood draw in relation to the previous dose. CONCLUSIONS: A real-time, IT-based intervention that links the timing of levels with medication administration might have a more substantial impact. PMID- 24225747 TI - Occult hematologic malignancy in routine tonsillectomy specimens: a single institutional experience and review of the literature. AB - OBJECTIVES: Handling of tonsillectomy specimens often includes gross and histologic examination. The published incidence of occult malignancy in benign appearing tonsils is vanishingly rare, and consequently some propose omitting histologic analysis in young patients without clinical risk factors for malignancy or grossly suspicious features. METHODS: At our institution, an occult Burkitt lymphoma in a grossly benign-appearing tonsil from an otherwise healthy 5 year-old prompted review of our cases. We retrospectively reviewed tonsillectomy findings over a 5-year period, excluding patients with known lymphoma or head and neck malignancies. A total of 740 patients were identified. All cases underwent gross and histologic examination. RESULTS: Four additional malignancies were diagnosed, including a clinically unsuspected lymphoma in a 14-year-old patient. In our experience, although most tonsillar malignancies present with suspicious clinical or gross findings, occult malignancies do occur. CONCLUSIONS: Recognition of these occult findings may facilitate early diagnosis and treatment; thus pathologic study of these specimens may still be justified. PMID- 24225748 TI - Quantification of expression of antigens targeted by antibody-based therapy in chronic lymphocytic leukemia. AB - OBJECTIVES: Anti-CD20 (rituximab), anti-CD52 (alemtuzumab), anti-CD22 (BL22, HA22), and anti-CD25 (Oncotac) are therapeutic options that are the mainstay or in preclinical development for the treatment of chronic lymphocytic leukemia (CLL). Studies suggest that levels of surface antigen expression may affect response to monoclonal antibody-based therapy. METHODS: Using the flow cytometric Quantibrite method (BD Biosciences, San Jose, CA) to determine antibodies bound per cell, we quantified the levels of surface expression of CD20, CD22, CD25, and CD52 in CLL cells from 28 untreated patients. RESULTS: The CLL cells in all cases expressed CD20, CD22, and CD52 but 4 (14%) cases were negative for CD25. Although the ranking of levels of expression from highest to lowest was CD52, CD20, CD22, and CD25, the level of antigen expression on any specific case could not be accurately predicted. CONCLUSIONS: Quantification of antigens might be useful in evaluating new antigens to target for therapy and may provide a systematic approach to selecting individualized therapy in CLL. PMID- 24225749 TI - Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis. AB - OBJECTIVES: p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS). METHODS: In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS. RESULTS: We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses. CONCLUSIONS: Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS. PMID- 24225750 TI - Automated evaluation of synovial and ascitic fluids with the Advia 2120 hematology analyzer. AB - OBJECTIVES: The purpose of this study was to determine if the Advia 2120 hematology analyzer (Siemens Healthcare Diagnostics, Deerfield, IL) can accurately quantify both WBCs and the proportion of neutrophils from synovial and ascitic body fluids. METHODS: We analyzed 60 samples on the Advia and compared the results with manual counts and smear reviews. We also assessed the effect of adding hyaluronidase to the samples. WBC counts and the proportion of neutrophils reported by the hematology analyzer were harmonized and highly correlated with manual counts and fluid smear reviews. RESULTS: The addition of hyaluronidase to the synovial fluid consistently increased the WBC counts on both manual and automated analysis (P < .001). CONCLUSIONS: We conclude that the Advia hematology analyzer can be used for WBC and neutrophil counting of cells in synovial and ascitic fluids. Hyaluronidase should be added before manual or automated counting of cells in synovial fluids. PMID- 24225751 TI - Histologic findings and clinical characteristics in acutely symptomatic ulcerative colitis patients with superimposed Clostridium difficile infection. AB - OBJECTIVES: To examine biopsy specimens for histologic features suggestive of Clostridium difficile infection in patients with ulcerative colitis (UC). METHODS: Nine patients with UC had colonic biopsy specimens taken during a symptomatic flare that coincided with positive C difficile (C difficile+) tests. Twenty-eight controls were biopsied during a UC flare but tested negative for C difficile. We reviewed the slides for evidence of pseudomembranes, ischemic-like changes, degree of colitis, and lamina propria hemorrhage. RESULTS: In C difficile+ patients, 4 (44.4%) of 9 had microscopic pseudomembranes compared with 11% in controls (P < .05). Other histologic/clinical features were not predictive. CONCLUSIONS: Although the presence of microscopic pseudomembranes suggests C difficile infection in patients with UC, sensitivity and specificity are poor; biopsy findings do not reliably detect this infection in patients with UC. PMID- 24225752 TI - p63 expression in Merkel cell carcinoma predicts poorer survival yet may have limited clinical utility. AB - OBJECTIVES: To determine the clinical utility of p63 expression, which has been identified in several cohorts as a predictor of poorer prognosis in Merkel cell carcinoma (MCC). METHODS: Immunohistochemistry was used to determine p63 expression on MCC tumors from 128 patients. RESULTS: Of the patients, 33% had detectable p63 expression. p63 Positivity was associated with an increased risk of death from MCC (hazard ratio, 2.05; P = .02) in a multivariate Cox regression model considering stage at presentation, age at diagnosis, and sex. Although p63 expression correlated with diminished survival in this largest cohort reported thus far, the effect was weaker than that observed in prior studies. Indeed, within a given stage, p63 status did not predict survival in a clinically or statistically significant manner. CONCLUSIONS: It remains unclear whether this test should be integrated into routine MCC patient management. PMID- 24225753 TI - Performance and abnormal cell flagging comparisons of three automated blood cell counters: Cell-Dyn Sapphire, DxH-800, and XN-2000. AB - OBJECTIVES: To compare two hematological analyzers-the DxH-800 (DxH; Beckman Coulter, Miami, FL) and XN-2000 (XN; Sysmex, Kobe, Japan)-with the Cell-Dyn Sapphire (SAPH; Abbott, Santa Clara, CA). METHODS: We analyzed 4,375 samples. Slide reviews were made in the presence of blast, abnormal lymphocyte, and immature granulocyte (IG) flags or nucleated RBC (NRBC) count. RESULTS: The analyzers exhibited excellent correlations for CBC and neutrophils but displayed a limit correlation for lymphocytes. The XN did not miss circulating blasts (0.5% 95% in microscopy). For NRBCs, the XN demonstrated a sensitivity of 90%; DxH, 74%; and SAPH, 29%. Only the XN demonstrated a correlation with microscopy, permitting a WBC six-part differential until 15% of NRBCs. The XN and DxH gave useful IG counts with a cutoff less than 5% and a WBC level more than 2,500/mm(3). For abnormal lymphocytes detection, only XN demonstrated sensitivity of more than 95%, but its specificity of 54% requires adaptation. CONCLUSION: The XN increases the sensitivity of abnormal cell detection compared with the other counters, permitting a seven-part differential between predefined levels, decreasing the slide review from 20% to 9%. PMID- 24225754 TI - Expression of the activating receptor, NKp46 (CD335), in human natural killer and T-cell neoplasia. AB - OBJECTIVES: To evaluate the expression of CD335 (NKp46), an activation receptor that is selectively expressed on natural killer (NK) cells. METHODS: We assessed CD335's potential utility as a diagnostic marker in 657 cases by flow cytometry and 410 cases by immunohistochemistry. RESULTS: We observed that CD335 was highly specific for NK cells in nonneoplastic tissues. Moreover, 61 (90%) of 68 of NK cell neoplasms demonstrated CD335 expression, whereas B-cell, myelomonocytic, and plasma cell neoplasms lacked expression. Notably, 16 (20%) of 82 mature T-cell neoplasms, particularly T-cell large granular lymphocytic leukemia, mycosis fungoides, and ALK+ anaplastic large cell lymphoma, aberrantly expressed CD335. CONCLUSIONS: Collectively, these data support the diagnostic utility of CD335 in evaluating hematopoietic malignancies and suggest that CD335 could be a useful target for selective immunotherapy in patients with mature NK and T-cell neoplasms. PMID- 24225755 TI - Evaluation of an external quality assessment program for HIV testing in Haiti, 2006-2011. AB - OBJECTIVES: To evaluate an external quality assessment (EQA) program for human immunodeficiency virus (HIV) rapid diagnostics testing by the Haitian National Public Health Laboratory (French acronym: LNSP). Acceptable performance was defined as any proficiency testing (PT) score more than 80%. METHODS: The PT database was reviewed and analyzed to assess the testing performance of the participating laboratories and the impact of the program over time. A total of 242 laboratories participated in the EQA program from 2006 through 2011; participation increased from 70 laboratories in 2006 to 159 in 2011. RESULTS: In 2006, 49 (70%) laboratories had a PT score of 80% or above; by 2011, 145 (97.5%) laboratories were proficient (P < .05). CONCLUSIONS: The EQA program for HIV testing ensures quality of testing and allowed the LNSP to document improvements in the quality of HIV rapid testing over time. PMID- 24225756 TI - Immunohistochemistry for the novel markers glypican 3, PAX8, and p40 (DeltaNp63) in squamous cell and urothelial carcinoma. AB - OBJECTIVES: To examine squamous cell carcinomas (SCCs) from diverse anatomic sites and invasive urothelial carcinomas (UCs) for expression of the oncofetal antigen glypican 3 (GPC3), the paired box transcription factor PAX8, and the DeltaN isoform of p63 (p40). METHODS: Immunohistochemistry for GPC3, PAX8, and p40 was performed on whole sections of 107 SCCs from 11 anatomic sites and 49 UCs; evaluation included extent and intensity of staining. RESULTS: GPC3 was detected in 20% of SCCs and 12% of UCs and PAX8 in 3% of SCCs, limited to the uterine cervix, and 10% of UCs. p40 Was found in 99% of SCCs and 96% of UCs. CONCLUSIONS: GPC3 expression is frequent in SCC/UC, awareness of which should guard against an incorrect diagnosis of hepatocellular carcinoma, while PAX8, limited in distribution, may have some use in suggesting a cervical or urothelial tract origin in a metastatic squamotransitional carcinoma of unknown primary. There is no drop-off in sensitivity for the diagnoses of SCC or UC with DeltaNp63 specific immunohistochemistry, and if this performance can be extended to other applications, p40 may supplant the dominant "pan-p63" antibody clone. PMID- 24225758 TI - Replacing urine protein electrophoresis with serum free light chain analysis as a first-line test for detecting plasma cell disorders offers increased diagnostic accuracy and potential health benefit to patients. AB - OBJECTIVES: To determine the most clinically effective diagnostic testing strategy for plasma cell disorders in the clinical laboratory. METHODS: Serum and urine samples from 2,799 patients with suspected plasma cell dyscrasias were tested by alternative diagnostic testing strategies consisting of serum protein electrophoresis (SPE) with either urine protein electrophoresis (UPE) or serum free light chain (sFLC) analysis. RESULTS: The combination of sFLC analysis and SPE had the greatest sensitivity (100%), detecting abnormalities in all 124 patients diagnosed with plasma cell disorders. Routine sFLC testing would have had much potential health benefit for two patients in the study population. First, a patient who had a markedly abnormal sFLC result was diagnosed with light chain deposition disease by renal biopsy, but no abnormality was detected by SPE or UPE. Second, a patient diagnosed with multiple plasmacytomas following biopsy of a lung tumor had a grossly abnormal sFLC result but an equivocal weak-positive SPE result, and no urine sample was received by the laboratory for the patient. CONCLUSIONS: Our study suggests that the combination of SPE and sFLC analysis is the most clinically effective first-line diagnostic testing strategy for detecting plasma cell disorders in the clinical laboratory. PMID- 24225757 TI - Improving diagnostic capability for HPV disease internationally within the NIH NIAID Division of AIDS Clinical Trial Networks. AB - OBJECTIVES: To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network. METHODS: A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit. RESULTS: Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested. CONCLUSIONS: The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement. PMID- 24225762 TI - Sysmex XE-5000 blast Q flag analysis. PMID- 24225759 TI - Traditional serrated adenoma of the colorectum: clinicopathologic implications and endoscopic findings of the precursor lesions. AB - OBJECTIVES: To investigate the clinicopathologic and endoscopic features of precursor lesions associated with traditional serrated adenomas (TSAs). METHODS: Mutation studies for BRAF, KRAS, PIK3CA, and EGFR and immunohistochemical staining for Ki-67 were performed on 107 TSAs from 104 patients. RESULTS: Nondysplastic hyperplastic polyp (HP) or sessile serrated adenoma/polyp (SSA/P) precursor lesions were found in 56 (52.3%) TSAs, among which 32 (57.1%) cases showed a flat-elevated lesion with a type II pit pattern during endoscopy. TSAs with an SSA/P precursor lesion were usually found in the proximal colon, while TSAs with an HP or with no precursor lesion were mainly located in the distal colon and rectum (P < .001). TSAs with a precursor lesion showed a lower frequency of conventional epithelial dysplasia and KRAS mutation as well as a higher frequency of BRAF mutation compared with those with no precursor lesion (P = .002, P < .001, and P < .001, respectively). CONCLUSIONS: A significant proportion of HP or SSA/P precursor lesions accompanied by TSAs can be detected by endoscopy based on both their flat-elevated growth and type II pit patterns. The heterogeneity of TSAs in terms of clinicopathologic and molecular features correlated with the status or type of precursor lesions. PMID- 24225763 TI - [Personalized medicine and breast cancer: anticipatory medicine, prognostic evaluation and therapeutic targeting]. AB - Breast cancer is now considered as a large collection of distinct biological entities, the management of which is increasingly personalized. Personalized medicine - defined as a medicine, which uses molecular profiles, notably genetic profiles, from patients and/or tumors to tailor therapeutic decisions - is now introduced in the management of breast cancer at any stages: screening and prevention of hereditary forms, prognostic and predictive evaluation of early breast cancer, and, more recently, novel clinical trials in advanced breast cancer, where genetic characterization of tumor tissue based on genomics, including next-generation sequencing tools, is used to drive specific therapeutic targeting. PMID- 24225769 TI - Water-oxidation catalysis by synthetic manganese oxides--systematic variations of the calcium birnessite theme. AB - Layered manganese oxides from the birnessite mineral family have been identified as promising heterogeneous compounds for water-oxidation catalysis (WOC), a key reaction for the conversion of renewable energy into storable fuels. High catalytic rates were especially observed for birnessites which contain calcium as part of their structures. With the aim to systematically improve the catalytic performance of such oxide materials, we used a flexible synthetic route to prepare three series of calcium birnessites, where we varied the calcium concentrations, the ripening times of the original precipitates and the temperature of the heat treatment following the initial synthetic steps (tempering) during the preparation process. The products were carefully analysed by a number of analytical techniques and then probed for WOC activity using the Ce(4+)-system. We find that our set of twenty closely related manganese oxides shows large, but somewhat systematic alterations in catalytic rates, indicating the importance of synthesis parameters for maximum catalytic performance. The catalyst of the series for which the highest water-oxidation rate was found is a birnessite of medium calcium content (Ca : Mn ratio 0.2 : 1) that had been subjected to a tempering temperature of 400 degrees C. On the basis of the detailed analysis of the results, a WOC reaction scheme for birnessites is proposed to explain the observed trends in reactivity. PMID- 24225771 TI - Palladium-catalyzed stereospecific cross-coupling of enantioenriched allylic alcohols with boronic acids. AB - In the presence of 2.5 mol% Pd2(dba)3-TMEDA (1 : 4), a range of enantioenriched allylic alcohols smoothly coupled with boronic acids in a highly regioselective fashion with inversion of configuration to afford structurally diverse alkenes in good yields with perfect retention of ee. PMID- 24225770 TI - Decreased perivascular CGRP-containing nerves in Otsuka Long-Evans Tokushima Fatty rats with insulin resistance and hypertension. AB - We previously reported that chronic hyperinsulinemia induced by drinking fructose elicited an abnormal neuronal regulation of vascular tone, which contributed to the development of hypertension. This study was designed to elucidate the possible mechanisms underlying the dysfunctional neuronal regulation of vascular tone induced by chronic hyperinsulinemia by comparing isolated mesenteric vascular beds from Otsuka Long-Evans Tokushima Fatty (OLETF) rats with those of control Long-Evans Tokushima Otsuka rat (LETO) rats. Insulin, triglyceride and total cholesterol levels in plasma, blood glucose concentrations, a glucose insulin index, systolic blood pressure and perivascular innervations were assessed using biochemical and immunohistochemical methods. Mesenteric vascular beds isolated from OLETF and LETO rats were perfused with a Krebs solution containing methoxamine, and changes in perfusion pressure in response to periarterial nerve stimulation (PNS) and the perfusion of vasoactive agents were measured. OLETF rats (8-25 weeks old) showed age-related increases in insulin, triglycerides, total cholesterol, blood glucose, the glucose-insulin index (homeostasis model assessment ratio (HOMA-IR)) and systolic blood pressure compared with LETO rats. In perfused mesenteric vascular beds, the PNS-induced adrenergic nerve-mediated vasoconstrictor responses in OLETF rats were significantly greater than those in LETO rats, whereas the PNS-induced calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator responses in OLETF rats were significantly smaller than those in LETO rats. In immunohistochemical experiments, the density of CGRP-immunopositive nerves in the mesenteric arteries of OLETF rats decreased significantly with age. The present findings suggest that the abnormal innervation of perivascular nerves in mesenteric resistance arteries induced by chronic hyperinsulinemia disturbs the neuronal regulation of vascular tone and may cause hypertension in OLETF rats. PMID- 24225772 TI - A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line. AB - Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 and Lewis tumor-bearing C57BL/6 mice were used for the evaluation of their activities. A MTT assay was used to determine the proliferation inhibition in A549 cells. Annexin-V/PI double staining as well as flow cytometry was performed to detect apoptosis and cell cycle status. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in serum. Furthermore, western blot analysis was applied to evaluate the expressions of proteins associated with cell death. Alkaloids or triterpenes showed a high anti proliferative activity in A549 cells, with IC50 values of 14.4 ug/mL and 9.3 ug/mL, respectively. The alkaloids and triterpenes combination could significantly inhibit tumor growth in tumor-bearing C57BL/6 mice, compared with alkaloids or triterpenes alone (7.5, 15, 30 g raw material/kg). The immune organs indexes including spleen index and thymus index were increased remarkably by the combination of alkaloids and triterpenes, whereas the levels of IL-6 and TNF alpha were up-regulated significantly. Moreover, Annexin-V/PI double staining and flow cytometry showed that the combination of alkaloids and triterpenes (1, 2 and 3 mg raw material/kg) could induce apoptosis and cause S cell cycle arrest in A549 cells. Western blot analysis also showed that their combination (2 mg raw material/kg) significantly down-regulated Bcl-2 expression and pro-casp8 level, whereas it remarkably increased the level of cleaved caspase-8 leading to apoptosis in A549 cells. These observations provide preliminary evidence that both alkaloids and triterpenes possess immune regulation and induction apoptosis activities. Their combination has a stronger activity than that of either class alone. Our findings suggested that these components might be beneficial for the prevention and treatment of NSCLC through a significant synergy effect. PMID- 24225773 TI - Synthesis of a versatile building block combining cyclen-derivative DO3A with a polyamine via a rigid spacer. AB - The five-step synthesis of a polydentate building block combining a cyclen-based macrocycle (DO3A) with N-(2-aminoethyl)propane-1,3-diamine, which are linked through the xylylen moiety as a rigid C-spacer is described. These two molecular parts were coupled by subsequent bromine atom substitution in 1,4 bis(bromomethyl)benzene. First, N-(2-aminoethyl)propane-1,3-diamine was protected by phthaloyl moieties and then it was reacted with 1,4-bis(bromomethyl)benzene to form (2-phthalimidoethyl)(3-phthalimido-prop-1-yl)(4-bromomethylbenzyl)amine (2). This compound underwent a substitution reaction with DO3A in the form of its tert butyl esters leading to the intermediate 1-{4-[(2-phthalimidoethyl)(3 phthalimidoprop-1-yl)aminomethyl]phenylmethyl}-4,7,10-tris(t-butoxy carbonylmethyl)-1,4,7,10-tetraazacyclododecane (3). The phthaloyl as well as the t-butyl protecting groups were removed in the next two reaction steps to form the final product 1-{4-[(2-aminoethyl)(3-aminoprop-1-yl)aminomethyl]phenylmethyl} 4,7,10-tris(carboxy-methyl)-1,4,7,10-tetraazacyclododecane (5). The intermediates 1-4 as well as the final product 5 were characterized by elemental analysis, mass spectrometry, and multinuclear (1H and 13C) and two-dimensional NMR spectroscopy. The final product 5 could serve as a potential building block in subsequent syntheses of binuclear complexes of lanthanides and/or transition metals. PMID- 24225774 TI - Synthesis and biological evaluation of RGD-conjugated MEK1/2 kinase inhibitors for integrin-targeted cancer therapy. AB - Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor- PD0325901--have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9a-g showed anti proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells. PMID- 24225775 TI - Processes of care in the multidisciplinary treatment of gastric cancer: results of a RAND/UCLA expert panel. AB - IMPORTANCE: There is growing interest in reducing the variations and deficiencies in the multidisciplinary management of gastric cancer. OBJECTIVE: To define optimal treatment strategies for gastric adenocarcinoma (GC). DESIGN, SETTING, AND PARTICIPANTS: RAND/UCLA Appropriateness Method involving a multidisciplinary expert panel of 16 physicians from 6 countries. INTERVENTIONS: Gastrectomy, perioperative chemotherapy, adjuvant chemoradiation, surveillance endoscopy, and best supportive care. MAIN OUTCOMES AND MEASURES: Panelists scored 416 scenarios regarding treatment scenarios for appropriateness from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores from 1 to 3 were considered inappropriate; 4 to 6, uncertain; and 7 to 9, appropriate. Agreement was reached when 12 of 16 panelists scored the scenario similarly. Appropriate scenarios agreed on were subsequently scored for necessity. RESULTS: For patients with T1N0 disease, surgery alone was considered appropriate, while there was no agreement over surgery alone for patients T2N0 disease. Perioperative chemotherapy was appropriate for patients who had T1-2N2-3 or T3-4 GC without major symptoms. Adjuvant chemoradiotherapy was classified as appropriate for T1 2N1-3 or T3-4 proximal GC and necessary for T1-2N2-3 or T3-4 distal GC. There was no agreement regarding surveillance imaging and endoscopy following gastrectomy. Surveillance endoscopy was deemed to be appropriate after endoscopic resection. For patients with metastatic GC, surgical resection was considered inappropriate for those with no major symptoms, unless the disease was limited to positive cytology alone, in which case there was disagreement. CONCLUSIONS AND RELEVANCE: Patients with GC being treated with curative intent should be considered for multimodal treatment. For patients with incurable disease, surgical interventions should be considered only for the management of major bleeding or obstruction. PMID- 24225778 TI - Reverse-CD mimics with flexible linkages offer adaptable cavity sizes for guest encapsulation. AB - Reverse-CD mimics with adaptable cavity sizes have been synthesized. The adaptability has been demonstrated through single crystal structure determination and guest binding studies. PMID- 24225776 TI - Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin. AB - The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3(ecto)), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2(Fu1-Fu2)), and Rspo2(Fu1-Fu2) in complex with ZNRF3(ecto), or RNF43(ecto). A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3(ecto) and RNF43(ecto) surface. Rspo binding enhances dimerization of ZNRF3(ecto) but not of RNF43(ecto). Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2. PMID- 24225777 TI - Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53 dependent endoplasmic reticulum stress. AB - Aberrant DNA hypermethylation is frequently found in tumor cells and inhibition of DNA methylation is an effective anticancer strategy. In this study, the therapeutic effect of DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) on colorectal cancer (CRC) was investigated. Zeb exhibited anticancer activity in cell cultures, tumor xenografts and mouse colitis-associated CRC model. It stabilizes p53 through ribosomal protein S7 (RPS7)/MDM2 pathways and DNA damage. Zeb-induced cell death was dependent on p53. Microarray analysis revealed that genes related to endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were affected by Zeb. Zeb induced p53-dependent ER stress and autophagy. Pro-survival markers of ER stress/UPR (GRP78) and autophagy (p62) were increased in tumor tissues of CRC patients, AOM/DSS-induced CRC mice and HCT116-derived colonospheres. Zeb downregulates GRP78 and p62, and upregulates a pro-apoptotic CHOP. Our results reveal a novel mechanism for the anticancer activity of Zeb. PMID- 24225779 TI - Bone grafts using autogenous tooth blocks: a case series. AB - OBJECTIVE: A case study was conducted to examine the clinical results and histologic healing of bone grafts performed using an autogenous tooth block (AutoBT block), which was developed recently and proprietary. STUDY DESIGN: Guided bone regeneration, extraction socket graft, sinus bone graft, and ridge augmentation were performed using autogenous tooth block graft material in 12 patients from March 2009 to June 2010. The clinical outcomes of each case were examined, and tissue specimens were collected from 1 case 2.5 months after the bone graft for histopathological analysis. RESULTS: All of the cases had successful bone graft results. One patient developed wound dehiscence after surgery, although favorable secondary healing was achieved. One implant resulted in osseointegration failure. A histopathologic examination was performed after 2.5 months and showed excellent bone healing due to osteoconduction. The AutoBT block was incorporated into the upper soft tissue, aponeurosis, and lower recipient bone. CONCLUSION: There were no notable complications associated with the bone transplant materials. The AutoBT block is clinically useful for a variety of bone grafts. PMID- 24225780 TI - Photodynamic therapy to treat periimplantitis. AB - AIM: : Periimplantitis is a bacterial complication after dental implants implantation. Photodynamic therapy (PDT) implies the use of low-power laser in combination with appropriate photosensitizer to increase the detoxification of the implant surfaces. Little information exists about PDT in the treatment of periimplantitis. A randomized comparative case-control study has been conducted with 20 patients and 20 controls to compare the efficacy of antimicrobial PDT versus surgical therapy in patients with periimplantitis, who have received dental implants with rough surfaces. MATERIALS AND METHODS: In the surgery group, mucoperiosteal flap surgery was used with scaling on implant surfaces and debridement of granulation tissue. Microbiologic testing was evaluated before and after intervention treatment, at 12 and 24 weeks in the study subjects. DISCUSSION: Total anaerobic counts of bacteria did not differ significantly between patients assigned to receive PDT and those assigned to receive surgical therapy (mean, 95.2% and 80.85%, respectively). PDT was associated with a significant decrease in bleeding scores (P = 0.02) as well as inflammatory exudation (P = 0.001). CONCLUSION: Treatment with PDT in patients with periimplantitis was not associated with major reduction of total anaerobic bacteria on the rough surfaces of dental implants as compared with surgical therapy. A significantly lower proinflammatory index of periimplantitis was observed in the PDT group at 24 weeks of follow-up. PMID- 24225781 TI - Is BMF central for anoikis and autophagy? PMID- 24225782 TI - Electron transport in purified glyoxysomal membranes from castor-bean endosperm. AB - Glyoxysomes isolated from castor-bean (Ricinus communis L.) endosperm were treated with water, 0.2 M KCl, 1 M KCl, or 0.1 M Na2CO3. Glyoxysomal sacs, i.e. membranes which retained some visible matrix, resulted from the treatments with water and KCl. Glyoxysomal ghosts, i.e. intact membranes free of matrix, were only obtained following treatment with carbonate. The ghosts were free of activities of matrix enzymes, particularly palmitoyl-CoA oxidation, isocitrate dehydrogenase (EC 1.1.1.42) and isocitrate lyase (EC 4.1.3.1), and contained only negligible amounts of malate synthase (EC 4.1.3.2), malate dehydrogenase (EC 1.1.1.37), beta-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.98) and catalase (EC 1.11.1.6). Distribution and appearance of membrane-associated particles in the protoplasmic and ectoplasmic faces of freeze-fracture replicas of the glyoxysomal membrane were the same in intact tissue, isolated glyoxysomes, and ghosts. Membranes purified by treatment with 0.2 M KCl or 0.1 M carbonate catalyzed the reduction of cytochrome-c when NADH or NADPH was provided as the electron donor. beta-Oxidation, localized in the matrix, could be linked to reduction of cytochrome-c or ferricyanide when purified membranes were combined with the matrix supernatant. Cytochrome-c could also be reduced by coupling enzyme activities in the matrix, NADP-isocitrate dehydrogenase or malate dehydrogenase, with those of the membrane. These results indicate that electrons from beta oxidation, malate oxidation or isocitrate oxidation can be transferred directly to the redox components of the glyoxysomal membrane. We, therefore, conclude that any NADH and NADPH formed by enzymes in the matrix can be recycled continuously within the organelle. PMID- 24225783 TI - Electron-microscopic analysis of ground elder (Aegopodium podagraria L.) lectin: evidence for a new type of supra-molecular protein structure. AB - The lectin of ground elder (Aegopodium podagraria L.) was investigated electron microscopically after negative staining with uranyl salts. Affinity-purified preparations of this glycoprotein were highly heteromorphous as they contained small particles approximately 4.6 nm in diameter and very large particles of different shapes. Among the latter, circular and helicoidal structures were the most regular in appearance. The circles were 9.3 nm in diameter, whereas the helices were 9 nm or 20 nm in diameter and up to 60 nm in length. After photographic enhancement, pictures of the molecules indicated that both the larger structures and the small particles could be obtained in pure forms by gel filtration of the lectin on Sepharose 4B. Since the former were the only constituents of the excluded fraction (Mr>5000000), whereas they were totally absent in the fraction eluting with an apparent molecular weight of about 500000, these supra-molecular structures revealed by the electron microscope cannot be artefacts generated during preparation of the lectin for electron-microscopic observation. PMID- 24225784 TI - Water droplets and ice deposits in leaf intercellular spaces: redistribution of water during cryofixation for scanning electron microscopy. AB - An experimental study is described of the formation of extracellular deposits on the surfaces of cells in freeze-fractured, frozen-hydrated primary leaves of Phaseolus vulgaris examined by low-temperature scanning electron microscopy. The deposits, observed under a range of experimental conditions, consisted of (a) droplets with diameters of 1.5 to 3.0 MUm, (b) droplets with diameters of 10 to 30 MUm, (c) crystals with diameters of 1.0 to 6.0 MUm, and (d) granules with diameters up to 0.15 MUm. The types of deposit were influenced by specimen cooling rate, and their distribution was influenced by the direction of the thermal gradient during cooling. All deposits were predominantly water ice. The quantities of deposited water (up to 4.0% of the leaf water content) increased as the cooling rate was reduced. It is concluded that the ice deposits were primarily artefacts of cryofixation and do not represent the location of water in vivo, as recently suggested. We propose that the deposits arose in four main ways: (1) displacement of water from underlying cells by a pressure wave resulting from the volume increase of intracellular water as it freezes, (2) evaporation of water from warmer cells and its condensation onto colder cells, (3) withdrawal of water from underlying cells by extracellular ice crystallization, (4) condensation of pre-existing water vapour in the intercellular spaces onto cells. The significance of the findings is discussed in relation to the use of lowtemperature scanning electron microscopy in studies of plant morphology and for localizing water and soluble ions within plant cells and tissues. PMID- 24225785 TI - Effects of specific inhibitors on the coordination of the concentrations of ribulose-bisphosphate-carboxylase subunits and their corresponding mRNAs in the alga Chlorogonium. AB - Investigations were carried out on the effects of inhibitors of transcription and translation on the concentrations of the subunits of the plastid enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPCase) and their corresponding mRNAs in the unicellular green alga Chlorogonium elongatum Dangeard. The light-induced increase of nuclear-coded small-subunit mRNA was strongly inhibited by alpha amanitin while the increase of plastid-coded large-subunit mRNA was only weakly affected: Consequently, the mRNAs of the two subunits were present in very different proportions. Nevertheless, the light-induced increase of both subunits was strongly reduced by alpha-amanitin to the same degree, and hence the ratio of their concentrations was not affected compared with the untreated control cells. The effect of cycloheximide on the subunit mRNAs was similar to but weaker than that of alpha-amanitin. Again the increases in the subunit levels were strongly inhibited to the same degree. By contrast, rifampicin and chloramphenicol inhibited the light-induced increase of large-subunit mRNA more strongly than that of small-subunit mRNA, but the differences were less distinct than those caused by alpha-amanitin and cycloheximide. Again, the increase in both subunits was inhibited almost to the same extent. These results - especially those of the alpha-amanitin experiments - clearly show that the fine coordination of the RuBPCase subunits occurs posttranscriptionally at the level of translation and-or degradation. This conclusion was confirmed by pulse-chase experiments. Inhibition of the synthesis of the large subunits by chloramphenicol resulted - as also found by other authors-in a degradation of excess small subunits in the plastid. On the other hand, inhibition of the concentration of small subunits caused a proportionate reduction in the synthesis of large subunits, but no rapid degradation of large subunits could be detected. Therefore, the fine coordination of both subunits of RuBPCase is achieved by the degradation of an excess of small subunits, while the level of large subunits is adapted to the small subunit concentration, probably by adjustment of translation of the large-subunit mRNA. Furthermore, our experiments with alpha-amanitin and cycloheximide allow us to conclude that in the blue-light induction of large-subunit mRNA in the plastid the nucleocytoplasmic compartment is not directly involved. PMID- 24225786 TI - Identification of oxindole-3-acetic acid, and metabolic conversion of indole-3 acetic acid to oxindole-3-acetic acid in Pinus sylvestris seeds. AB - Oxindole-3-acetic acid (OxIAA) has been identified in germinating seeds of Scots pine (Pinus sylvestris) using gas chromatography-mass spectrometry. Seeds germinated for 5 d contained 2.7 ng OxIAA.g(-1) (dry weight) whereas ungerminated seeds contained 0.2 ng.g(-1). Isotopically labelled OxIAA was formed in seeds incubated with [1'-(14)C]-, [2'-(14)C]- or [(2)H5]indole-3-acetic acid. PMID- 24225787 TI - Implications for cytoplasmic pH, protonmotice force, and amino-acid transport across the plasmalemma of Riccia fluitans. AB - By means of pH-sensitive microelectrodes, cytoplasmic pH has been monitored continuously during amino-acid transport across the plasmalemma of Riccia fluitans rhizoid cells under various experimental conditions. (i) Contrary to the general assumption that import of amino acids (or hexoses) together with protons should lead to cytoplasmic acidification, an alkalinization of 0.1-0.3 pHc units was found for all amino acids tested. Similar alkalinizations were recorded in the presence of hexoses and methylamine. No alkalinization occurred when the substrates were added in the depolarized state or in the presence of cyanide, where the electrogenic H(+)-pump is inhibited. (ii) After acidification of the cytoplasm by means of various concentrations of acetic acid, amino-acid transport is massively altered, although the protonmotive force remained essentially constant. It is suggested that H(+)-cotransport is energetically interconnected with the proton-export pump which is stimulated by the amino-acid-induced depolarization, thus causing proton depletion of the cytoplasm. It is concluded that, in order to investigate H(+)-dependent cotransport processes, the cytoplasmic pH must be measured and be under continuous experimental control; secondly, neither DeltapH nor the protonmotive force across a membrane are reliable quantities for analysing a proton-dependent process. PMID- 24225788 TI - Inhibition and promotion by light of the accumulation of translatable mRNA of the light-harvesting chlorophyll a/b-binding protein of photosystem II. AB - The amount of in-vitro translatable mRNA of the light-harvesting chlorophyll a/b binding protein (LHCP) of photosystem II strongly increases in darkness (D) after a 5-min red-light pulse while continuous illumination of mustard seedlings with far-red (FR), red or white light leads only to a slight increase in the amount of translatable LHCP-mRNA. No increase can be observed after a long-wavelength FR (RG9-light) pulse. However, a FR pretreatment prior to the RG9-light pulse strongly increase LHCP-mRNA accumulation in subsequent D. This is not observed in the case of the mRNA for the small subunit of ribulose-1.5-bisphosphate carboxylase. The increase of LHCP-mRNA in D after a FR pretreatment can be inhibited by a reillumination of the seedlings with FR. The inhibition of LHCP mRNA accumulation during continuous illumination with FR and the strong increase in D following a FR illumination was found to be independent of chlorophyll biosynthesis since no correlation between chlorophyll biosynthesis and translatable LHCP-mRNA levels could be detected. Even strong changes in the amount of intermediates of chlorophyll biosynthesis caused by application of levulinic acid or 5-aminolevulinic acid did not affect LHCP-mRNA levels. Therefore, we conclude that the appearance of LHCP-mRNA is inhibited during continuous illumination, even though illumination leads to a storage of a light singal which promotes accumulation of translatable LHCP-mRNA in D. PMID- 24225789 TI - Ribonuclease in plant vacuoles: purification and molecular properties of the enzyme from cultured tomato cells. AB - A ribonuclease which was previously shown to be located in isolated vacuoles from suspension-cultured cells of tomato (Lycopersicon esculentum L.; Abel and Glund 1986, Physiol. Plant. 66, 79-86) has been purified to near homogeneity. Purification was up to 55000-fold with a yield of about 20%. The vacuolar origin of the protein was evidenced by comparing its electrophoretic mobility, isoelectric point, pH-optimum for activity and other properties with that of the RNA-degrading activity present in isolated vacuoles. The molecular weight of the native single polypeptide chain was estimated at 17500 and 20300 by gel filtration and sedimentation analysis, respectively. The enzyme hydrolyzed only single-stranded RNA with a mode of action that was endonucleolytic. The vacuolar ribonuclease had no requirement for divalent metal ions, and did not exhibit phosphomonoesterase (EC 3.1.3.1; EC 3.1.3.2) and phosphodiesterase (EC 3.1.15.1; EC 3.1.16.1) activity. The specificity of the enzyme has been studied by using homopolyribonucleotides as substrates. The end-products obtained were the respective nucleoside 2':3'-cyclic monophosphates and, to minor extents, the corresponding nucleoside 3'(2')-monophosphates. According to these observations, the vacuolar ribonuclease from tomato can be classified as ribonuclease I (EC 3.1.27.1). PMID- 24225791 TI - Gradient in the degree of Crassulacean acid metabolism within leaves of Kalanchoe daigremontiana. AB - Leaves of the Crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perr., about 3.3 mm thick, showed higher rates of net CO2 exchange through the lower than through the upper surface during day and night, although the lower surface received only a small fraction of the light which was incident on the upper surface. Nocturnal acidification was more pronounced in cells from the lower than from the upper portion of leaves. The lower activity of the exposed side of these long-lived succulent leaves may be related to the potentially adverse effects of excessive light. PMID- 24225790 TI - Blue-light control of mRNA level and transcription during chloroplast differentiation in photomixotrophic and photoautotrophic cell cultures (Chenopodium rubrum L.). AB - In cell suspension cultures of Chenopodium rubrum maintained under photomixotrophic or photoautotrophic growth conditions the differentiation of chloroplasts is strictly blue-light-dependent. During this process of greening the steady-state concentration of mRNAs coding for plastid proteins increases rapidly in response to blue-light exposure as was determined by a dothybridization technique employing cloned DNA sequences complementary to these nuclear and plastid transcripts (light-harvesting chlorophyll a/b protein, rbcs, rbcl, psbA, atpB, atpE). Red light suppresses this response when applied at an advanced stage of chloroplast development. Indications are that blue-light dependency of chloroplast differentiation is a common feature of cultured plant cells irrespective of their metabolism. A DNA-protein complex with an active RNA polymerase ("transcriptionally active chromosome"; TAC) which specifically transcribes the plastid genes of its endogenous DNA has been isolated and purified from chloroplasts of light-grown cells. Quantitative analyses of these in-vitro transcripts show that the activity of TAC from cells grown in blue light prior to isolation is significantly higher than that of TAC from cells raised in red light under the same conditions. The results indicate that blue light enhances the transcription of plastid genes encoding prominent proteins. This response could account for the observed rise in transcript level in vivo. PMID- 24225792 TI - Some characteristics of anion transport at the tonoplast of oat roots, determined from the effects of anions on pyrophosphatedependent proton transport. AB - The effects of anions on inorganicpyrophosphate-dependent H(+)-transport in isolated tonoplast vesicles from oat (Avena sativa L.) roots were determined. Both fluorescent and radioactive probes were used to measure formation of pH gradients and membrane potential in the vesicles. Pyrophosphate hydrolysis by the H(+)-translocating pyrophosphatase was unaffected by anions. Nonetheless, some anions (Cl(-), Br(-) and NO3-) stimulated H(+)-transport while others (malate, [Formula: see text] and iminodiacetate) did not. These differential effects were abolished when the membrane potential was clamped at zero mV using potassium and valinomycin. Stimulation of H(+)-transport by Cl(-) showed saturation kinetics whereas that by NO3- consisted of both a saturable component and a linear phase. For Cl(-) and NO3-, the saturable phase had a K m of about 2 mol.m(-3). The anions that stimulated H(+)-transport also dissipated the membrane potential (Deltapsi.) generated by the pyrophosphatase. It is suggested that the stimulatory anions cross the tonoplast in response to the positive Deltapsi generated by the pyrophosphatase, causing dissipation of Deltapsi and stimulation of DeltapH, as expected by the chemiosmotic hypothesis. The work is discussed in relation to recent studies of the effects of anions on ATP-dependent H(+) transport at the tonoplast, and its relevance to anion accumulation in the vacuole in vivo is considered. PMID- 24225793 TI - Race cultivar-specific differences in callose deposition in soybean roots following infection with Phytophthora megasperma f.sp. glycinea. AB - Primary roots of soybean (Glycine max (L.), Merrill, cv. Harosoy 63) seedlings were inoculated with zoospores from either race 1 (incompatible, host resistant) or race 3 (compatible, host susceptible) of Phytophthora megasperma f.sp. glycinea and total callose was determined at various times after inoculation. From 4 h onward, total callose was significantly higher in roots showing the resistant rather than the susceptible response. Local callose deposition in relation to location of fungal hyphae was determined in microtome sections by its specific fluorescence with sirofluor and was quantified on paper prints with an image-analysis system. Callose deposition, which occurs adjacent to hyphae, was found soon after inoculation (2, 3 and 4 h post inoculation) only in roots displaying the resistant response, and was also higher at 5 and 6 h after inoculation in these resistant roots than in susceptible roots. Early callose deposition in the incompatible root-fungus reaction could be a factor in resistance of soybean against P. megasperma. PMID- 24225794 TI - Photorespiratory N donors, aminotransferase specificity and photosynthesis in a mutant of barley deficient in serine: glyoxylate aminotransferase activity. AB - A mutant of Hordeum vulgare L. (LaPr 85/84) deficient in serine: glyoxylate aminotransferase (EC 2.6.1.45) activity has been isolated. The plant also lacks serine: pyruvate aminotransferase and asparagine: glyoxylate aminotransferase activities. Genetic analysis of the mutation strongly indicates that these three activities are all carried on the same enzyme protein. The mutant is incapable of normal rates of photosynthesis in air but can be maintained at 0.7% CO2. The rate of photosynthesis cannot be restored by supplying hydroxypyruvate, glycerate, glutamate or ammonium sulphate through the xylem stream. This photorespiratory mutant demonstrates convincingly that photorespiration still occurs under conditions in which photosynthesis becomes insensitive to oxygen levels. Two major peaks and one minor peak of serine: glyoxylate aminotransferase activity can be separated in extracts of leaves of wild-type barley by diethylaminoethyl sephacel chromatography. All three peaks are missing from the mutant, LaPr 85/84. The mutant showed the expected rate (50%) of ammonia release during photorespiration but produced CO2 at twice the wild-type rate when it was fed [(14)C]glyoxylate. The large accumulation of serine detected in the mutant under photorespiratory conditions shows the importance of the enzyme activity in vivo. The effect of the mutation on transient changes in chlorophyll a fluorescence initiated by changing the atmospheric CO2 concentration are presented and the role of the enzyme activity under nonphotorespiratory conditions is discussed. PMID- 24225795 TI - Amylase activity and growth in internodes of deepwater rice. AB - Isoelectrofocusing, product analysis, thermal denaturation studies and affinity chromatography on cycloheptaamylose-Sephadex were used to identify the amylolytic enzymes in internodes of deepwater rice (Oryza sativa L.). Amylolytic activity in internodes of deepwater rice consists of alpha-amylase (sometimes separated into two isoforms) and of beta-amylase. During submergence of whole plants, alpha amylase activity increases in young, growing internodes, but beta-amylase activity declines. Although non-growing, mature internodes contain higher levels of beta-amylase than do the elongating younger internodes, the effect of submergence on amylase activities in both tissues follows the same trend. Submergence, gibberellic acid (GA3) and ethylene all promote alpha-amylase activity in growing and non-growing internodes of excised deepwater-rice stem sections. Inhibitor studies showed that submergence and ethylene promote alpha amylase activity in the absence of endogenous gibberellin (GA), and GA3 enhances alpha-amylase activity when ethylene action is inhibited. Therefore, ethylene and GA appear to increase alpha-amylase activity independently of each other. Enhanced alpha-amylase activities are probably responsible for the mobilization of carbohydrates which are needed to support internode elongation during submergence of deepwater rice. PMID- 24225796 TI - Phytochrome-induced flavonoid biosynthesis in mustard (Sinapis alba L.) cotyledons. Enzymic control and differential regulation of anthocyanin and quercetin formation. AB - Phytochrome-induced increases in enzyme activities for phenylalanine ammonia lyase (EC 4.3.1.5) and chalcone isomerase (EC 5.5.1.6), and in amounts of the related end products, anthocyanin and the flavonol, quercetin, were measured in cotyledons of mustard (Sinapis alba L.). There was no correlation between the activities of these enzymes and the rate of anthocyanin accumulation; however, some correlation was found with the quercetin accumulation rate. Since anthocyanin and flavonol accumulation is spatially separated in mustard (flavonols in the upper epidermis, anthocyanin in the lower epidermis), it was possible to measure anthocyanin-associated phenylalanine ammonia-lyase independently. This activity correlated well with the accumulation rate for anthocyanin during the first few hours after induction. The phytochrome effect on anthocyanin formation differed from that on quercetin formation: anthocyanin was strongly induced by continuous far-red light and by both continuous red light and red light pulses, whereas quercetin was only effectively induced by continuous far-red light. PMID- 24225797 TI - A plant lipid and the platelet-activating factor stimulate ATP-dependent H(+) transport in isolated plant membrane vesicles. AB - A plant lipid was isolated from zucchini (Cucurbita pepo L.) membranes and from soybean (Glycine max [L.] Merr) phospholipids by thinlayer chromatography and further purified by high-performance liquid chromatography. This plant lipid was chromatographically very similar to the platelet-activating factor, an ether phospho-lipid with hormone-like properties found in mammals. Both the plant lipid and the platelet-activating factor stimulated ATP-dependent H(+) transport in isolated membrane vesicles from zucchini hypocotyls. PMID- 24225799 TI - A simple, effective method of determining efficiency of boiler dust remover. PMID- 24225798 TI - Photomorphogenesis in Chenopodium album. Effects of supplementary far-red light on the kinetics of stem extension. AB - The effects of far-red light given against a background of white light on the stem-extension kinetics of three-week-old, light-grown Chenopodium album seedlings were investigated. Under white light alone, the stems (cotyledon-to apex) extended almost exactly logarithmically with time. Under these conditions the increase in log [stem length in mm] per hour was approx. 3.7.10(-3), equivalent to about 1% per h during both skoto-and photoperiods. Supplementary far-red given throughout each photoperiod massively stimulated extension. The calculated logarithmic extension rate, however, slowly returned to that of the controls, following an initial large increase. This is predicted by a model in which far-red light linearly increases the extension rate of individual internodes which arise at an exponentially increasing rate. The behaviour of the model is also consistent with critical experiments in which far-red was given as a pre-treatment or transiently, as well as with other published data. Far-red stimulation of logarithmic extension rate in successive photoperiods was closely and linearly correlated with calculated phytochrome photoequilibrium. Daily short periods of supplementary far-red were especially potent in accelerating extension; the plants seemed least responsive at the end of the photoperiod. PMID- 24225800 TI - Migration of pollutants in groundwater. V. Modelling the removal of DNAPL droplets by flushing. AB - Mathematical models are developed for the flushing of droplets of dense nonaqueous phase liquids (DNAPLs) distributed in aquifers. The kinetics of the diffusion of dissolved volatile organic compound (VOC) from the droplets into the moving liquid is included in the models. Models are developed for the flushing of DNAPL droplets in lab columns, in aquifers with a one-dimensional radial flow field and in quiescent aquifers in which a single well screened at the bottom is used to bring about the flushing. Some representative results are given. PMID- 24225801 TI - Migration of pollutants in groundwater. VI. Flushing of DNAPL droplets/ganglia. AB - Models for describing the flushing of DNAPL from contaminated aquifers are developed, and the dependence of the calculated cleanup times on the model parameters is explored. Diffusion transport from isolated DNAPL droplets, from low-permeability porous spherical domains containing distributed DNAPL droplets, and from low-permeability porous planar lamellae containing distributed DNAPL is analyzed, and the resulting expressions then coupled with the equations for advective transport of dissolved VOC by means of natural uniform flow and a system of injection and recovery wells generating a two-dimensional flow field. The models are readily run on currently available microcomputers. The results of computations with the models are consistent with the severe tailing and slow rates of remediation which are generally observed when DNAPLs are removed by flushing. PMID- 24225802 TI - A method of rapid identification of the most important ecological problems in polluted areas. AB - A comprehensive method is presented for the evaluation of the living elements of the environment by way of an example of an area situated within the emission range of a non ferrous metal works. The exposure of particular components of the environment is shown using the method of indices, taking into consideration the action of pollutants on the most essential and sensitive receptors. Methods of exposure reduction are also suggested. The proposed method may be helpful in land use planning in polluted environments and can also be applied to determine the sequence of activities aimed at diminishing the effects of pollution. PMID- 24225803 TI - Substrate influence on epiphytic lichens. AB - The origin of the presence of soil elements in the epiphytic lichen Lecanora conizaeoides was investigated in an area of heavily polluted soil (The Broekpolder The Netherlands). Analysis results of lichens, bark and tree rings of the supporting trees indicated that for As, Co, Cr, Cu, Fe, Hg, Sc and V the levels in lichens may be considered to originate from wet and dry deposition. The Cd, Mn and Zn levels in lichens might have originated from both wet and dry deposition and the substrate bark. For these three elements, in particular, accumulation characteristics in lichens should be further investigated. PMID- 24225804 TI - Trace elements and organochlorines in the shoalgrass community of the lower Laguna Madre, Texas. AB - Our objectives were to measure concentrations of seven trace elements and 14 organochlorine compounds in sediment and biota of the shoalgrass (Halodule wrightii) community of the lower Laguna Madre of south Texas and to determine whether chemicals associated with agriculture (e.g. mercury, arsenic, selenium, organochlorine pesticides) were highest near agricultural drainages. Arsenic, mercury, selenium, lead, cadmium, and organochlorines were generally at background concentrations throughout the lower Laguna Madre. Nickel and chromium concentrations were exceptionally high in shrimp and pinfish (Lagodon rhomboides), which is difficult to explain because of no known anthropogenic sources for these trace elements. For sediment and blue crabs (Callinectes sapidus), mercury was highest near agricultural drainages. Also, DDE was more frequently detected in blue crabs near agricultural drainages than farther away. In contrast, selenium concentrations did not differ among collecting sites and arsenic concentrations were lowest in shoalgrass, blue crabs, and brown shrimp (Penaeus aztecus) near agricultural drainages. PMID- 24225805 TI - Bacterial secondary production in freshwater measured by(3)H-thymidine incorporation method. AB - Bacterial secondary production in lake water was measured by(3)H-thymidine incorporation into DNA. The application of the method to freshwater systems studied required (1) thymidine concentration > 10 nM (10-25 nM) evaluated from isotope dilution by varying the specific activity of labeled thymidine, (2) short incubation periods less than 1 hour, and (3) partial purification of the DNA fraction for measuring(3)H-thymidine incorporation. During 2 diel studies, bacterial productivity was compared to phytoplankton primary production and extracellular release of organic carbon. Diel changes in bacterial growth suggested substantial activity during the morning and evening. Possible mechanisms of control of bacterial growth, such as extracellular release of organic carbon, are discussed. PMID- 24225806 TI - Nutritional relationships among microorganisms in an epilithic biofilm community. AB - Previous studies of an epilithic algal-bacterial community in a pristine mountain stream suggested that heterotrophic bacteria were responding to the metabolic activities of the phototrophic population. Subsequent studies were performed to follow the flow of labeled carbon, from its initial inorganic form, through the trophic levels of the mat community. A majority of primary production metabolites were excreted by the algal population during active growth; this shifted to an incorporation into cellular material as phototrophic activity declined. Results suggest that there was a direct flux of soluble algal products to the bacterial population, with little heterotrophic utilization of dissolved organics from the overlying stream water. Both phototrophic productivity and bacterial utilization of algal products peaked at approximately the same time of year. Activity of the diatom-dominated algal population declined as silica concentrations in the stream water dropped, leading to a situation in which the sessile bacteria were substrate limited. These events resulted in an almost complete disappearance of the community in early September. PMID- 24225807 TI - Physical determinants of microbial colonization and decomposition of plant litter in an Arctic Lake. AB - Physical effects on the microbial colonization and decomposition of plant litter in an oligotrophic lake were studied in Toolik Lake, Alaska. Colonization, measured by adenosine triphosphate (ATP) analysis, and decomposition, measured by weight loss, were correlated with depth of incubation, light, and temperature. The effects of turbulence, light, and temperature were studied in microcosm experiments. A 10 degrees C increase (above ambient) in temperature caused a doubling in the amount of microbial colonization and a 50% increase in decomposition. Light intensity had no quantitative effect on either colonization or decomposition. Turbulence experiments conducted in Toolik Lake showed significant differences in decomposition between natural turbulence and no turbulence. Elevated temperature (20 degrees C, which was 10 degrees C above ambient), high turbulence, and total darkness changed the composition of the litter microbiota, causing a shift from a bacterially dominated microbiota to one dominated by large filamentous forms, as revealed by scanning electron microscopy. This study shows the importance of these physical factors in determining the rate at which plant litter is colonized and degraded in aquatic environments. PMID- 24225808 TI - Transport of microbial biomass through the North Inlet ecosystem. AB - Tidal fluctuations and transports of total microbial biomass (measured as adenosine triphosphate [ATP]) were investigated at three marsh creeks comprising the major transfer points between the North Inlet marsh and the adjoining aquatic ecosystems. Two creeks, Town Creek and North Jones Creek, form the inlet mouth and are the only marsh-ocean exchange points. The third creek, South Jones Creek, connects to a brackish water embayment. The creeks were simultaneously sampled every 1.5 hours for 50 consecutive hours during neap tides (four tidal cycles) and 50 consecutive hours during spring tides of each season. At the inlet, ATP concentration fluctuated in phase with the tide during winter and fall and out of phase with the tide during the spring. Fluctuation patterns at South Jones Creek were irregular. The highest ATP concentrations were during the spring (mean=2.17 mg of ATP per m(3)) and the lowest concentrations were during the winter (mean=0.65 mg of ATP per m(3)). Net transports of ATP varied from tidal cycle to tidal cycle with regard to direction of transport (import or export) and magnitude. Net transports were small compared to large instantaneous transports and only 4 of 22 determinations of net transport were different from zero transport. PMID- 24225809 TI - Biotic adjustments to changing salinities in the Great Salt Lake, Utah, USA. AB - The salinity of the Great Salt Lake, Utah has changed greatly over the past 23 years. The north arm of the lake has increased in salinity and decreased in overall biological diversity, whereas the south arm has decreased in salinity and increased markedly in biological diversity. PMID- 24225810 TI - Measurement of Electron Transport System (ETS) activity in soil. AB - Electron transport system (ETS) activity was measured in amended and nonamended soil by measuring the reduction of 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride (INT) to iodonitrotetrazolium formazan (INT-formazan), which can be easily extracted with methanol without interference from other compounds found in soil. A high correlation between ETS activity and oxygen consumption was observed. This technique allows rapid quantitative measurements of microbial ETS activity in soil. PMID- 24225811 TI - Powder puff spiroplasma: A new epiphytic mycoplasma. AB - A spiroplasma (strain PPS1) isolated from healthy flowers ofCalliandra haematocephala in Florida has been found to be a member of a serogroup of the Spiroplasmataceae. It is distinct fromSpiroplasma citri and from other described spiroplasmas as determined by growth inhibition, fluorescent antibody, and ELISA serological tests. PPS1 was also distinguished fromS. citri and several other spiroplasmas by the guanine + cytosine content of its DNA. PPS1 requires sterol for growth, is inhibited by digitonin, grows at 20-30 degrees C, and does not hydrolyze arginine or urea. The ready isolation of this and similar organisms from surfaces of healthy plants emphasizes that caution should be exercised in attempts to isolate cell wall-less prokaryotes from the interior of diseased plants. Although some strains of spiroplasmas are known as insect pathogens in nature, the ecological role(s) of the flower-inhabiting spiroplasmas has yet to be fully determined. PMID- 24225812 TI - Segmented filamentous bacteria in the rodent small intestine: Their colonization of growing animals and possible role in host resistance toSalmonella. AB - The establishment and proliferation of a model population of autochthonous surface-associated microorganisms in the small bowel of growing rats (2-12 weeks of age) was studied. Segmented filamentous bacteria on the distal ileal villi were examined by scanning electron microscopy (SEM) and countedin situ by transect line analysis. In young animals, these bacteria first colonized the villous base, but occupied all areas on the villus by adult age. Their distribution on Peyer's patches was also noted.In growing animals, colonization of the ileal villi by filamentous bacteria was significantly correlated to the development of host resistance to fatal infection by orally-dosedSalmonella enteritidis. In animals givenSalmonella and examined by SEM and transmission EM (TEM), the pathogen was seen only on ileal tissue surfaces, predominantly the villous base, from which the autochthonous population was absent. Conversely, in animals with filamentous bacteria,Salmonella surface colonization was not observed. The results suggest a possible protective role for the surface flora in the small bowel. PMID- 24225814 TI - Evaluation of a proposed surface colonization equation usingThermothrix thiopara as a model organism. PMID- 24225813 TI - Yeasts from exudates ofQuercus, Ulmus, Populus, andPseudotsuga: New isolations and elucidation of some factors affecting ecological specificity. AB - The yeast flora associated with exudates ofQuercus, Ulmus, Populus, andPseudotsuga was examined in the light of new isolations in geographic areas different from those in previous reports. Application of multivariate analytic methods indicated that geographic distance, although a meaningful ecological factor, is largely overshadowed by host tree specificity, provided that yeast community physiological profiles and not yeast taxa, are used as ecological descriptors. Some physiological attributes used in classifying yeasts were identified as particularly important in shaping the yeast communities of those trees. The possible divergence between these attributes and those generally considered taxonomically useful is discussed. PMID- 24225815 TI - The reverse remodeling effect of mesenchymal stem cells is independent from the site of epimyocardial cell transplantation. AB - OBJECTIVE: The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)-induced failing hearts. METHODS: Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. RESULTS: The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% +/- 1.4%, and RV-MSC, 39.2% +/- 2.6%, vs sham group, 29.8% +/- 3.7%; P < 0.001), without significance between the MSC groups (P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% +/- 3.4%; and RV-MSC, 8.1% +/- 2.2%; P < 0.05), without significance between the two MSC groups (P = 0.927). CONCLUSIONS: Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings. PMID- 24225816 TI - Effect of sodium bicarbonate and Beta-alanine on repeated sprints during intermittent exercise performed in hypoxia. AB - PURPOSE: To investigate the separate and combined effects of sodium bicarbonate and beta-alanine supplementation on repeated sprints during simulated match play performed in hypoxia. METHODS: Study A: 20 recreationally active participants performed two trials following acute supplementation with either sodium bicarbonate (0.3 g.kg-1BM) or placebo (maltodextrin). Study B: 16 recreationally active participants were supplemented with either a placebo or beta-alanine for 5 weeks (6.4 g.day-1 for 4 weeks, 3.2 g.day-1 for 1 week), and performed one trial before supplementation (with maltodextrin) and two following supplementation (with sodium bicarbonate and maltodextrin). Trials consisted of 3 sets of 5 * 6 s repeated sprints performed during a football specific intermittent treadmill protocol performed in hypoxia (15.5% O2). Mean (MPO) and peak (PPO) power output were recorded as the performance measures. RESULTS: Study A: Overall MPO was lower with sodium bicarbonate than placebo (p = .02, 539.4 +/- 84.5 vs. 554.0 +/- 84.6 W), although there was no effect across sets (all p > .05). Study B: There was no effect of beta-alanine, or cosupplementation with sodium bicarbonate, on either parameter, although there was a trend toward higher MPO with sodium bicarbonate (p = .07). CONCLUSIONS: The effect of sodium bicarbonate on repeated sprints was equivocal, although there was no effect of beta-alanine or cosupplementation with sodium bicarbonate. Individual variation may have contributed to differences in results with sodium bicarbonate, although the lack of an effect with beta-alanine suggests this type of exercise may not be influenced by increased buffering capacity. PMID- 24225817 TI - Increasing organ donation in Hispanic Americans: the role of media and other community outreach efforts. AB - IMPORTANCE: The growing demand for organs continues to outpace supply. This gap is most pronounced in minority populations, who constitute more than 40% of the organ waiting list. Hispanic Americans are particularly less likely to donate compared with other minorities for reasons that remain poorly understood and difficult to change. OBJECTIVE: To determine whether outreach interventions that target Hispanic Americans improve organ donation outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prospective before-after study of 4 southern California neighborhoods with a high percentage of Hispanic American residents. We conducted cross-sectional telephone surveys before and 2 years after outreach interventions. Respondents 18 years or older were drawn randomly from lists of Hispanic surnames. Awareness, perceptions, and beliefs regarding organ donation and intent to donate were measured and compared before and after interventions. INTERVENTION: Television and radio commercials about organ donation and educational programs at 5 high schools and 4 Catholic churches. MAIN OUTCOMES AND MEASURES: Number of survey participants who specify intent to donate. RESULTS: A total of 402 preintervention and 654 postintervention individuals participated in the surveys. We observed a significant increase in awareness of and knowledge about organ donation and a significant increase in the intent to donate (17.7% vs 12.1%; adjusted odds ratio, 1.55 [95% CI, 1.06-2.26; P = .02]). CONCLUSIONS AND RELEVANCE: Focused donor outreach programs sustain awareness and knowledge and can significantly improve intent to donate organs in the Hispanic American population. These programs should continue to be evaluated and implemented to influence donor registration. PMID- 24225818 TI - Somatic hybridization in Citrus: navel orange (C. sinensis Osb.) and grapefruit (C. paradisi Macf.). AB - Protoplasts of navel orange, isolated from embryogenic nucellar cell suspension culture, were fused with protoplasts of grapefruit isolated from leaf tissue. The fusion products were cultured in the hormone-free medium containing 0.6 M sucrose. Under the culture conditions, somatic embryogenesis of navel orange protoplasts was suppressed, while cell division of grapefruit mesophyll protoplasts was not induced. Six embryoids were obtained and three lines regenerated to complete plants through embryogenesis. Two of the regenerated lines exhibited intermediate morphological characteristics of the parents in the leaf shape. Chromosome counts showed that these regenerated plants had expected 36 chromosomes (2n=2x=18 for each parent). The rDNA analysis using biotin-labeled rRNA probes confirmed the presence of genomes from both parents in these plants. This somatic hybridization system would be useful for the practical Citrus breeding. PMID- 24225819 TI - Estimation of recombination parameters between a quantitative trait locus (QTL) and two marker gene loci. AB - A new method is described to obtain maximum likelihood estimates of recombination frequencies between quantitative trait loci (QTL) and marker gene loci; it is based on Fisher's method of scoring and numerical differentiation. The method is applied to data from chromosome-doubled monoploid lines of barley originating from the F1 generation of a cross between two well-adapted barley varieties. The lines segregated for marker gene loci ddt (DDT resistance) and s (short rachilla hairs) on chromosome 7. The quantitative trait of single-kernel weight was found statistically significantly associated with locus s, but not with locus ddt. The association is ascribed to a QTL designated Kw1. It could not be ascribed to pleiotropism at locus s since the recombination frequency between s and Kw1 (0.26+/-0.09) differed significantly from zero. The recombination frequencies between Kw1 and ddt and between ddt and s were 0.42+/-0.07 and 0.31+/-0.03, respectively, suggesting the locus order ddt, s, Kw1. The segregation ratio for alleles in locus Kw1 was estimated to be 43?57, which is not significantly different from a 1?1 ratio. Means and standard deviations of single-kernel weight for lines with either of the two Kw1 alleles were estimated; the Kw1 locus accounted for 25% of the variance of the single kernel weight. PMID- 24225820 TI - Inheritance of resistance to bacterial blight in common bean. AB - Inheritance of resistance to common bacterial blight in the trifoliate leaf, plant canopy, and pods was controlled by a single major gene. Additive followed by dominance effects were more important than epistatic interactions. Narrow sense heritability values ranged from 0.18 to 0.87 for trifoliate leaf, from 0.26 to 0.76 for canopy, and from 0.11 to 0.36 for pods. Observed gains from selection for resistance were higher than expected gains. Implications of these results in breeding for resistance are discussed. PMID- 24225821 TI - Monosomic analysis of tissue culture response in wheat (Triticum aestivum L.). AB - The ability of immature embryos of wheat (Triticum aestivum L.) to respond in cell culture was examined in crosses between the 'Wichita' monosomic series and a highly regenerable line, 'ND7532'. Segregation in disomic controls and 13 monosomic families showed a good fit to a monogenic ratio indicating a qualitative mode of inheritance. Segregation in the cross involving monosomic 2D showed a high frequency of regeneration (93.6%) and high callus growth rate (1.87 g/90 days) indicating that 2D is a critical chromosome. Modifying genes may be located on other chromosomes. Substitution of chromosomes from a low regenerable cultivar 'Vona' further indicated that the group 2 chromosomes, in particular chromosome 2D, possess genetic factors promoting callus growth and regeneration. PMID- 24225822 TI - Comparison of the organization and expression of mtDNA of fertile and male sterile sugar beet varieties (Beta vulgaris L.). AB - Analysis of minicircle occurrence in different samples of sugar beet mitochondrial (mt) DNA invalidates the postulated relationship between cytoplasmic male sterility (CMS) phenotype and the absence of minicircle c and d. In high molecular weight mt DNA, two types of restriction patterns are found for fertile genomes and only one type for the CMS; in spite of the multiplicity of crosses carried out by plant breeders, all the CMS varieties analyzed seem to have derived from the original cytoplasm discovered by Owen in 1945. Southern hybridizations with mitochondrial genes coding for cytochrome oxidase subunits II and III, ATPase subunits alpha, 6 and 9 and 26S ribosomal RNA indicate that gene organization is different between fertile and sterile genomes but similar in all fertile genomes. Transcription analysis with the same genes indicate several differences between fertile and sterile varieties but also within some fertile varieties. These results suggest that the mt genome found in male-sterile sugar beet may originate not from modifications of the fertile mitochondrial genome but from a particular source of cytoplasm, of which a possible origin is discussed. PMID- 24225823 TI - Interspecific hybridization between Vigna radiata (L.) Wilczek and V. glabrescens. AB - Interspecific hybrids of the mungbean, Vigna radiata (L.) Wilczek (2n=22) and V. glabrescens (2n=44) were generated with the aid of embryo culture. V. glabrescens x V. radiata hybrids were recovered via germination of the immature embryos. Reciprocal hybrids were obtained via shoot formation from embryonic callus. The authenticity of the hybrids was determined by morphological characteristics, chromosome number, and isozyme patterns. The hybrids were highly sterile upon selfing, but backcrossing to the diploid parent yielded viable seeds. Some of the plants resembled the diploid parent morphologically while others resembled neither parent. The backcross plants were sufficiently fertile to give a large number of mature, selfed seeds. Plants obtained differed morphologically and in their isozyme patterns from either parent, indicating introgression. These progeny populations will be used as bridging materials to transfer pest resistance from the wild tetraploid to the cultivated mungbean. PMID- 24225824 TI - Selection of higher regenerative callus and change in isozyme pattern in rice (Oryza sativa L.). AB - Calli were initiated from seedling roots in rice (Oryza sativa L. var. Tadukan) and subcultured at 45-day intervals on MS medium supplemented with 2 mg/l 2,4-D. Sectors of callus which differentiated shoot meristems (green spots) under the same 2,4-D concentration were selected from the calli subcultured 90 days after initiation. The selection was continued for about 2 years. Responses to 2,4-D between original and selected lines differed considerably, although differentiation was not generally seen in rice callus in the presence of 2 mg/l 2,4-D. After 180 days, calli of the selected line differentiated into numerous shoot-bud primordia and grew out new callus tissues under 2 mg/l 2,4-D concentration; the frequency of the differentiation exceeded 90%. On the other hand, no calli of non-selected line differentiated into shootbuds under 2 mg/l 2,4-D, and the frequency of the shootbud was only about 50% under lower 2,4-D concentration (0.1 mg/l). The pattern and activity of peroxidase isozyme varied markedly between calli of the selected and non-selected lines. First, two strong peroxidase bands which show fast mobility and one intermediate peroxidase band with slow mobility were detected only in the calli of selected line. Secondly, changes in band pattern of proteins separated by SDS-PAGE were observed. In the calli of selected line, there was a loss of the polypeptide bands with molecular weight of 24 and 42 K in the selected calli, but they were clearly present in the unselected line. The appearance of new peroxidase isozyme bands and loss of polypeptide bands, change in response to auxin and increased ability for shoot bud differentiation are closely correlated to each other. PMID- 24225825 TI - Diversity within and between populations of two sympatrically distributed Hordeum species in Jordan. AB - The diversity of two sympatrically distributed barley species (Hordeum vulgare L. and Hordeum spontaneum C. Koch.) has been assessed for 7 morphometric and 13 qualitative traits. Phenotypically, Hordeum vulgare was more stable than Hordeum spontaneum for all morphometric traits; this is a reflection of domestication and selection. The overall diversity indexes were 0.546+/-0.125 and 0.502+/-0.113 for Hordeum vulgare and Hordeum spontaneum, respectively (P=0.095). However, Hordeum spontaneum expressed a higher level of diversity for most qualitative traits. The observed similarity for a number of diversity indexes is probably due to gene flow between the two species. PMID- 24225826 TI - Chromosomal control of the aminopeptidases of wheat and its close relatives. AB - Isoelectric focussing was used to separate the isozymes of aminopeptidase of wheat and its relatives. Three distinct homoeoallelic sets of genes have been shown to be present. AMP-1, controlled by genes on the long arms of group 6, has previously been described, but two new systems, AMP-2 (group 4) and AMP-3 (group 7) are described here. The three systems are distinguished by their electrophoretic characteristics, by their genetic control and by their substrate specificity. Intervarietal, interspecific and intergeneric polymorphism has been observed at most of the loci. A further set of isozymes, AMP-4, was detected but the chromosomal control of these could not be determined. PMID- 24225827 TI - Optimising visual selection in early clonal generations of potato based on genetic and economic considerations. AB - In 1985, 1986 and 1987, 600 clones were visually assessed at harvest on plant appearance. The clones were harvested 80 days after planting in the first year, in the following years after approximately 80 days as well as after 145 days. The correlation coefficients between years and between harvest times were low to medium. Simulating different selection intensities using the performance of these 600 clones in two successive years, the relation between selection pressure in the first year and the retained proportion of well performing clones in the second year was described. Including the costs of testing, the most economic selection procedure was calculated. This procedure consisted in testing 1,579 first-year clones and 499 second-year clones for every 100 third-year clones required. The optimal period of the main evaluation in the second clonal year is at ware potato harvest time. This selection procedure also provides good selection possibilities for underwater weight and foliage maturity. PMID- 24225828 TI - In vitro selection for methomyl resistance in CMS-T maize. AB - Many plants resistant to methomyl (Lannate), an insecticide which selectively damages maize with the Texas (T) type of cytoplasmic male sterility (CMS-T), were obtained by in vitro selection and also without selection. The selection procedure used 0.6-0.7mM methomyl and callus from CMS-T versions of several field and sweet corn genotypes (W182BN, Wf9, P39, MDM1, SW1 and hybrids of SW1, IL766A1, IL766A2, and 442 with W182BN-N). Addition of 1 mM methomyl to the regeneration medium greatly reduced recovery of methomyl-sensitive escapes. Resistance was linked with reversion to male fertility and maternally inherited. Most progeny of resistant plants exhibited stable maternally inherited resistance for two generations in field tests. First-generation progeny of seven culture derived plants segregated for resistance and sensitivity; this suggests that ears of these seven regenerants were cytoplasmically chimeral. Resistance to methomyl was associated with resistance to T toxin from Helminthosporium maydis race T and with changes in mitochondrial physiology. Prolonged culture (14-16 months versus 6-8 months) increased the frequency of resistance among both selected and non selected regenerants. Little or no resistance was found among regenerants from certain genotypes. Selection with methomyl may be useful for production of improved sweet corn lines and as a source of mitochondrial mutants. This system is also convenient for studies of the effects of nuclear background and of culture and selection systems on the generation of cytoplasmic mutants. PMID- 24225829 TI - Multiple reconstruction of barley karyotype resulting in complete cytological marking of the chromosome complement. AB - A new reconstructed barley karyotype, PK88, which is a quadruple homozygote for three unequal translocations, 1-2, 3-4, 5-7, and one pericentric inversion in chromosome 6, was studied. As a result of these chromosome rearrangements, a complete cytological marking of the complement has been achieved. Due to the specific intra or interchromosomal transfer of particular bands, Giemsa staining of somatic chromosomes provided clear-cut indications about the localization of translocation and inversion breakpoints. It was established that the long arms of chromosomes 1, 2, 4, 5 and 7 and the short arm of chromosome 3 have been involved in interchanges 1-2, 3-4, and 5-7. The breakpoints of pericentric inversion proved to be located proximally to the short (satellite) arm and distally in the long arm of chromosome 6. PK-88 offers an essential gain in resolution power and extension of the areas of application in cytogenetics over other reconstructed karyotypes produced so far in barley. PMID- 24225830 TI - The pleiotropic phenotype of tomato cells selected for altered response to Fusarium oxysporium f. sp. lycopersici cell wall components. AB - With the aim of better understanding in vitro host-parasite interactions, tomato cell lines selected for altered response to Fusarium oxysporum f. sp. lycopersici cell wall components were further characterized. Particularly, their behaviour in dual culture in regard to both fungal inhibition and peroxidase activation was analysed and selected, and control cell clones were screened for esopolysaccharide content and toxin tolerance. Interclonal differences in growth response to 2,4-D and DMSO and the capacity to grow on a medium devoid of hormones (habituation) were taken as parameters representative of physiological variability not directly correlated with the response to pathogens. Significant differences between clones selected for increased (F+) and decreased (F-) response to fungal elicitors were found for pathogen inhibition, peroxidase and esopolysaccharide content, toxin tolerance being reduced in F but not significantly different from the control in F+. As expected, clonal variability for the response to 2,4-D and DMSO, although significant, was not connected with hostparasite interactions. The data reported thus show that selection for a character (response to elicitors), probably critical for the response to pathogens, may lead to the recovery of genotypes showing a set of modifications suggestive of a cascade of events leading to active defense. PMID- 24225831 TI - Molecular, cytogenetic and morphological characterization of somatic hybrids of dihaploid Solanum tuberosum and diploid S. brevidens. AB - Fifty-eight somatic hybrid plants, produced both by chemical (11) and electrical fusion (47) of protoplasts of dihaploid Solanum tuberosum and S. brevidens, have been analysed by molecular, cytological and morphological methods. The potentially useful euploid plants constituted 34% of the total, of which 20% were tetraploid and 14% hexaploid; the remainder were aneuploid at the tetraploid, hexaploid and octoploid levels. Analysis of chloroplast DNA showed that 55% of hybrids contained chloroplasts from S. brevidens and 45% from S. tuberosum. Hexaploids, the products of three protoplasts fusing together, were analyzed with specific DNA probes, and this revealed that nuclear genome dosages could be either 2?1 S. tuberosum?S. brevidens, or vice-versa. Chloroplast types of hexaploids were not influenced by nuclear genome dosage, and all six possible combinations of genome dosage and chloroplast types were found amongst tetraploids and hexaploids. To examine the morphology of the hybrid population and its possible relation to the chromosome number and chloroplast DNA type, 18 morphological characteristics were measured on greenhouse-grown plants and analyzed by principal component and canonical variate analyses. Both analyses showed that nuclear ploidy has the most prominent influence on the overall morphology of the hybrids. Differential parental genome expression in the morphology of the hybrids is discussed. These results provide useful data on the range of genetic combinations that can be expected to occur amongst somatic hybrid plants. PMID- 24225832 TI - Expression and inheritance of inserted markers in binary vector carrying Agrobacterium rhizogenes-transformed potato (Solanum tuberosum L.). AB - Transgenic shoots were regenerated from eight diploid potato hairy root clones obtained by transformation with Agrobacterium rhizogenes harboring next to its wild-type Ri-plasmid a binary vector containing the neomycin phosphotransferase and the beta-glucuronidase genes. The plants exhibited the typical hairy root phenotype. Of the plants isolated, 58% were tetraploid and 38% were diploid. Flowering and tuberization was much better in the diploid than in the tetraploid plants. Transgenic plants formed a significantly larger root system when grown on kanamycin-containing medium as compared to growth on kanamycin-free medium. Direct evidence for genetic transformation was obtained by opine, neomycin phosphotransferase and beta-glucuronidase assays, and by molecular hybridization. Fourteen flowering diploid plants were reciprocally crossed with untransformed S. tuberosum plants, but only six were successful. Seedlings obtained from four crosses showed that all traits were transmitted to the offspring. Molecular analysis confirmed the presence of multiple integrations (copies) of both vector T-DNA and Ri-T-DNA. The genetic data, furthermore, suggest that the traits derived from Ri-T-DNA and binary vector T-DNA are linked, as no recombination between the different traits was observed. PMID- 24225833 TI - Localization of the T-DNA on marker chromosomes in transformed tobacco cells by in situ hybridization. AB - Chromosome and molecular analyses were conducted on tobacco cells which had been transformed by the T-DNA of the Ti-plasmid. These analyses showed that there were specific chromosome rearrangements in the transformed cells (marker chromosomes). There was a positive correlation between the number of marker chromosomes per cell and the oncogenic potential of the transformed cells. However, we show, using the Southern hybridization method, that the TL fragment of T-DNA, but not the TR, clearly hybridizes with nuclear DNA. In situ hybridization was used to locate the insertion site of T-DNA: the hybridization signal was found on a small metacentric chromosome. This chromosome may occur single or translocated onto other chromosomes, to make marker chromosomes. Thus, by locating the T-DNA, we have confirmed the correlation between the marker chromosomes and the oncogenic potential. PMID- 24225834 TI - Embryo-callus-regenerated hybrids and their colchicine-induced amphiploids between Elymus canadensis and Secale cereale. AB - Intergeneric hybrids recovered through plant regeneration from embryo callus culture and their colchicine-induced amphiploids were obtained from a cross of Elymus canadensis with Secale cereale (cv 'Gazeller'). The embryo-callus regenerated F1 plants grew vigorously to maturity and regrew well after clipping, while the embryo-rescued F1 died of hybrid necrosis before maturity. Most of the morphological characters of the sterile F1 hybrids were intermediate between the parents, but tiller number and dry matter yield were higher than the parents. Amphiploids from these F1 plants had improved fertility but were less vigorous than the F1 plants. The predominance of univalents in the F1 and bivalents in the amphiploids indicated that the genomes S, H, and R were distinct. However, the occasional occurrence of multivalents reflected a random, intergenomic or intragenomic pairing. The mean chromosome associations of the F1 (2n=21, SHR), the C0 amphiploids (2n=42, SSHHRR), and the C1 amphiploid (2n=40) at metaphase I (MI) were 16.51I+2.05II+0.06III+0.02IV+0.02V, 2.20I+19.87II +0.02IV, and 7.10I+16.37II+0.04III+0.02IV, respectively. These amphiploids could be exploited as new germplasm for forage crop improvement by controlled introgression and backcrosses to the parents. PMID- 24225835 TI - Extent of genetic variability of endosperm esterases in Triticum aestivum L. 2n=6x=42. AB - Genetic variability of endosperm esterase has been studied in 42 cultivars of Triticum aestivum L. 2n=6x=42. Different techniques, including sequential electrophoresis and electrofocusing, have been used with various substrates and esterase inhibitors. The electrophoretic patterns in each cultivar are described. Chromosomal location using the nullitetrasomic and ditelosomic lines of Chinese Spring was carried out in order to relate and/or locate the esterase genes to specific chromosomes. Most of the esterase isozymes located were in the long arm of the chromosomes of the homoeology group 3; but we have found six located in the short arms, five of them in the chromosome 3AS and one in the 3DS. This location increases the number of esterase genes described, because no esterase genes had been described so far in short arms of chromosomes of the homoeology group 3. The genetic control is discussed and, according to our results, between 12 and 15 loci, organized in five "compound loci", control the endosperm esterases in wheat. Also one "modifier" gene modifying the mobility of two esterase bands and present in all the cultivars studied is postulated. PMID- 24225836 TI - Method to estimate genotype probabilities at individual loci in farm livestock. AB - A Bayesian method to estimate genotype probabilities at a single locus using information on the individual and all its relatives and their mates has been developed. The method uses data over several generations, can deal with large numbers of individuals in large livestock families and allows for missing information. It can be extended to multiple alleles and can be used for autosomal or sex-linked loci. The allele frequencies and the form of expression (dominance, penetrance) must be specified. An algorithm using the method and involving an iterative procedure has been developed to calculate the genotype probabilities for practical use in livestock breeding. The method and algorithm were used to determine the accuracy of estimating genotype probabilities of sires for a female sex-limited trait, such as genetic variants of milk proteins. Data were similated and genotype probabilities estimated for 100 sires (20 replicates) with 3, 6 and 12 female offspring per sire, for different population frequencies, for additive and dominance gene action and for variable genotypic expression. Such simulation is useful in the design of testing systems for the use of information on specific genetic loci in selection. PMID- 24225837 TI - Protoplast-fusion-mediated transfer of organelles from Microcitrus into Citrus and regeneration of novel alloplasmic trees. AB - Iodoacetate-treated Citrus protoplasts from embryogenic nucellar calli of Sour orange (C. aurantium) or from Rough lemon (C. jambhiri) were fused with gamma irradiated protoplasts from a related genus, Microcitrus. The fused protoplasts were cultured to obtain colonies and micro-calli. Micro-calli derived from these two fusion combinations were isolated, propagated and differentiated into embryos, which subsequently regenerated trees having the morphology of Sour orange or Rough lemon. These intergeneric fusions resulted in mitochondria with novel DNA, indicating recombination between the chondriomes of Citrus and Microcitrus. Chloroplast DNA analyses of fusion-derived embryos indicated that they contained the chloroplasts of either fusion-partner or a mix of these chloroplasts. Later plastome analyses of leaves from fully differentiated plants showed that cybrids having Rough lemon morphology had either Rough lemon or Microcitrus chloroplast DNA, indicating complete sorting out of chloroplasts. Likewise, sorting out of Microcitrus chloroplasts was detected in a cybrid plant having Sour orange morphology. PMID- 24225838 TI - Fast-germinating low beta-glucan mutants induced in barley with improved malting quality and yield. AB - Mutation breeding has been used to improve the speed of germination in the high yielding spring barley variety Troubadour. Five mutants were selected which combined fast germination and good agronomic performance. Two of these mutants yielded significantly more than did Troubadour over eight environments, and showed a clear improvement in their malting quality through an increase in extract yield. The improvement in malting quality appeared to be due to a decrease in the beta-glucan content, which seemed to enhance the germination speed and thus the starch degradation. The improvement in grain yield is postulated to be due to a better early growth caused by the enhanced germination speed. All the described changes could theoretically be explained by a single mutation event in each of the mutant genotypes, affecting the quantity of beta glucans present in the endosperm. PMID- 24225839 TI - An RFLP marker in tomato linked to the Fusarium oxysporum resistance gene I2. AB - The locus, I2, which in tomato confers resistance against Fusarium oxysporum f. sp. lycopersici race 2, was introgressed into Lycopersicon esculentum from the wild species L. pimpinellifolium (P.I. 126915). We searched for restriction fragment length polymorphisms (RFLPs) between nearly isogenic lines (NILs) in clones that map to the region introgressed from the wild species. Since I2 maps to chromosome 11, we used DNA clones from this chromosome as hybridization probes to Southern blots containing bound DNA of the NILs digested with 23 restriction enzymes. Of the 14 chromosome 11 clones, 9 exhibited polymorphism. These clones were further hybridized to "verification" filters that contained DNA from resistant and susceptible L. esculentum varieties digested with the enzymes that gave the polymorphism. One clone, TG105, was found to be associated with I2; 19 susceptible lines showed a different RFLP with this probe than 16 resistant lines, including the original L. pimpinellifolium accession used as a source for the resistance gene. These results together with our mapping analysis indicate that TG105 is closely linked to the resistance gene. PMID- 24225840 TI - A novel approach for separating bacteriophages from other bacteriophages using affinity chromatography and phage display. AB - Practical applications of bacteriophages in medicine and biotechnology induce a great need for technologies of phage purification. None of the popular methods offer solutions for separation of a phage from another similar phage. We used affinity chromatography combined with competitive phage display (i) to purify T4 bacteriophage from bacterial debris and (ii) to separate T4 from other contaminating bacteriophages. In 'competitive phage display' bacterial cells produced both wild types of the proteins (expression from the phage genome) and the protein fusions with affinity tags (expression from the expression vectors). Fusion proteins were competitively incorporated into the phage capsid. It allowed effective separation of T4 from a contaminating phage on standard affinity resins. PMID- 24225841 TI - Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. AB - Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. During eversion, peripodial epithelial cells lose apico-basal polarity and adherens junctions, and become migratory and invasive--a process similar to an epithelial-mesenchymal transition. Loss of netrinA inhibits the breakdown of cell-cell junctions, leading to eversion failure. In contrast, the Netrin receptor Frazzled blocks eversion when overexpressed, whereas frazzled RNAi accelerates eversion in vitro. In peripodial cells Frazzled is endocytosed, and undergoes NetA-dependent degradation, which is required for eversion. Finally, we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis. PMID- 24225842 TI - Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3 CK20/CD44s/p53) and alpha-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia. AB - Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions especially in the setting of prior therapy. Various markers including CK20, CD44s, and p53 have been used as an adjunct in making this distinction; however, the utility of these markers in the posttreatment scenario is not fully established. alpha-Methylacyl-CoA racemase (AMACR) is a tumor-associated marker that is expressed in a subset of high-grade urothelial carcinomas but has not been studied in CIS. This study was undertaken to evaluate the immunoreactivity of CK20, CD44s, and p53 as a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3) in distinguishing CIS from its mimics and to compare its utility with AMACR in the diagnosis of CIS. A total of 135 specimens (7 benign ureters and 128 bladder biopsies-28 reactive, 33 posttherapy reactive, 43 CIS, 24 CIS posttherapy) were included in this study. Immunostaining for p53 (brown, nuclear), CD44s (brown, membranous), and CK20 (red, cytoplasmic and membranous) was performed as a cocktail, and the staining pattern was further classified as: malignant (full-thickness CK20 and/or full-thickness p53 with CD44s negativity), reactive/benign (CK20 limited to the umbrella cell layer, p53 negative, and CD44s positivity ranging from basal to full thickness), and indeterminate (CK20 and p53 positive but not full thickness and/or CD44s positive). AMACR staining was performed in 50 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak focal staining [<5% cells]) and positive (>=5%). The "IUN-3 malignant" pattern was observed in 84% of cases of CIS without a history of prior therapy and in 71% of the cases of CIS with a history of prior therapy. Cases with posttherapy reactive atypia showed an "IUN-3 reactive" pattern in 84% cases and "IUN-3 indeterminate" pattern in 16% of the cases; the IUN-3 malignant pattern was not identified in any of the cases. Benign and reactive urothelium (with and without a history of therapy) showed an IUN-3 reactive pattern and negative AMACR staining in all the cases (100%). AMACR positivity was observed in 78% of nontreated CIS cases and 50% of CIS posttherapy cases. In these cases, the IUN-3 cocktail showed an IUN-3 malignant pattern in 83% of untreated CIS cases and 88% of CIS posttherapy cases. AMACR positivity is a potentially useful marker of CIS. However, the IUN-3 malignant pattern is a more reliable indicator of CIS compared with AMACR, especially in the posttreatment setting. The simultaneous evaluation of all 3 markers (p53, CD44s, and CK20) in a single slide in the form of a cocktail is advantageous, especially in small biopsy specimens. PMID- 24225843 TI - Amylase alpha-1A (AMY1A): a novel immunohistochemical marker to differentiate chromophobe renal cell carcinoma from benign oncocytoma. AB - Chromophobe renal cell carcinoma (ChRCC) and oncocytoma present with a perplexing overlap of morphologic and immunohistochemical features. ChRCC have deletions in the 1p21.1 region including the amylase alpha-1A gene (AMY1A). No such deletions are found in oncocytoma. Instead, oncocytomas shared other deletions on chromosome 1: 1p31.3, 1q25.2, and 1q44. We performed AMY1A immunostaining on 75 oncocytomas (57 tissue microarray [TMA] cores, 18 whole slides) and 54 ChRCCs (20 TMA cores, 34 whole slides). Staining was assessed using the H-score method. The intensity was graded as follows: no staining=0, weak=1, moderate=2, and strong=3. The AMY1A immunostain preferentially stained the distal tubules and collecting ducts of normal kidney. All oncocytomas (100%) expressed AMY1A with an H-score that varied from 100 to 300 (mean 205). Mild to moderate heterogeneity in staining intensity was noted within a given oncocytoma. For oncocytomas, 87% (65/75) cases had H-scores of at least 120 with a mean score of 221. Notably, the 13% (10/75) of oncocytoma cases that had an H-score of 100 were derived from the TMA. A total of 87% (47/54) of the ChRCC cases were negative for the AMY1A immunostain. Of the ChRCC cases, 4% (2/54) showed very weak cytoplasmic staining (H-score of 70 each), which was less than the lowest H-score of oncocytoma cases. All 5 cases of ChRCC, which showed an H-score of 100 or more, were referred to as eosinophilic variants of ChRCC. Three of these 5 cases showed a very nondescript, diffuse staining of the cytoplasm. Two of these 5 cases showed an H-score of 130. We think that as the staining pattern of these 2 cases is similar to that of oncocytoma, they should be put in a category of renal oncocytic neoplasms favoring oncocytoma. This result shows that AMY1A staining could be very helpful in further classifying even a subset of the eosinophilic variants of ChRCC. The difference between ChRCC and oncocytoma was statistically significant (chi test, P<0.0001). All cases of clear cell RCC and papillary RCC were negative for AMY1A expression. Overall, sensitivity and specificity of AMY1A staining for oncocytoma was 100% (95% confidence interval, 0.95-1.00) and 96.75% (95% confidence interval, 0.93-0.99), respectively. Similarly, the sensitivity and specificity for distinguishing oncocytoma from ChRCC was 100% (95% confidence interval, 0.95 1.00) and 90.74% (95% confidence interval, 0.80-0.97), respectively. These data show that the novel marker AMY1A can be of great diagnostic utility when trying to differentiate ChRCC (classic and eosinophilic variant) and oncocytoma. PMID- 24225844 TI - Discontinuous foci of cancer in a single core of prostatic biopsy: when it occurs and performance of quantification methods in a private-practice setting. AB - In addition to clinical data, prostatic biopsy (Bx) reports orient urologists in outlining the patient's treatment options. Discontinuous involvement of a core by multiple foci of cancer is not infrequent; however, there is currently no consensus as to which method of quantification should be the standard. We applied 2 distinct approaches to quantify the length of cancer foci in the Bx and compared the results to prostatectomy (RP) parameters. All patients with matched Bx and RP treated by the same medical team between 2006 and 2010 were consecutively included in the study. Tumor extent in the Bx was estimated by multiple approaches, and the length was measured in millimeters. The subset of cases with discontinuous foci of cancer in a single core was initially reported by adding each foci and ignoring the benign intervening prostatic tissue, which was designated as additive quantification (AQ). Upon slide review, these foci were reassessed as a single focus and measured by linear quantification (LQ). RPs were partially embedded according to the International Society of Urological Pathology recommendations, and the percentage of tumor was evaluated with graphic precision. Mean percentage of the tumor in RP (%RP) and in the Bx were arbitrarily classified as limited (<6%) and nonlimited (>=6%). Bx parameters were then correlated with %RP and margin status. All methods of quantification of the tumor in the Bx obtained excellent correlation with %RP. LQ and AQ diverged in 14/38 patients, with a mean total length of cancer of 5.8 mm more than the length obtained by LQ in the same population, accurately upgrading 6/14 cases to nonlimited. This subset (LQ>AQ) was more often seen in Bx with significantly more positive cores (P=0.003) of predominantly Gleason score 7 and associated with positive surgical margins in RP (P=0.034) independent of %RP (21% vs. 19% in the margin-negative cases). However, in the subset of Bx in which the tumor infiltration was continuous (AQ=AL) positive margins were indeed associated with tumor extent (31% vs. 6% in margin-negative cases). Discontinuous foci of cancer in a single core were most often seen in Bx sampling nonlimited disease, and this event was associated with positive surgical margins. LQ of cancer improved the performance of the Bx in predicting RP tumor extent relative to the traditional millimetric sum. Our findings support the idea that discontinuous foci may represent undersampling of a larger irregular nodule; however, this study is based on routine reports and does not directly access tumor biology. PMID- 24225845 TI - Vitamin B12 deficiency in relation to functional disabilities. AB - This study was designed to assess whether symptoms, functional measures, and reported disabilities were associated with vitamin B12 (B12) deficiency when defined in three ways. Participants, aged 60 or more years of age, in 1999-2002 National Health and Nutrition Examination Surveys (NHANES) were categorized in relation to three previously used definitions of B12 deficiency: (1) serum B12 < 148 pmol/L; (2) serum B12 < 200 pmol/L and serum homocysteine > 20 MUmol/L; and (3) serum B12 < 258 pmol/L or serum methylmalonic acid > 0.21 MUmol/L. Functional measures of peripheral neuropathy, balance, cognitive function, gait speed, along with self-reported disability (including activities of daily living) were examined with standardized instruments by trained NHANES interviewers and technicians. Individuals identified as B12 deficient by definition 2 were more likely to manifest peripheral neuropathy OR (odds) (95% confidence intervals), p value: 9.70 (2.24, 42.07), 0.004 and report greater total disability, 19.61 (6.22, 61.86) 0.0001 after adjustments for age, sex, race, serum creatinine, and ferritin concentrations, smoking, diabetes, and peripheral artery disease. Smaller, but significantly increased, odds of peripheral neuropathy and total disability were also observed when definition 3 was applied. Functional measures and reported disabilities were associated with B12 deficiency definitions that include B12 biomarkers (homocysteine or methylmalonic acid). Further study of these definitions is needed to alert clinicians of possible subclinical B12 deficiency because functional decline amongst older adults may be correctable if the individual is B12 replete. PMID- 24225846 TI - Health-related quality of life in children with celiac disease: a study based on the Critical Incident Technique. AB - Celiac Disease (CD) is a chronic autoimmune disease triggered by dietary gluten. Gluten avoidance, which is the only available treatment for CD, could impact on quality of life of children with CD. We present the results of a qualitative study on the emotional impact of gluten free diet (GFD) on the everyday life of children affected with CD. We investigated 76 celiac patients aged 2-18 years (average age: 9.5 years). By using the Critical Incident Technique (CIT), we defined emotions related to difficulties and awkward situations experienced by the patients. Written answers to open-ended questions from either children (older than 8 years) and parents (children younger than 8 years) were analyzed qualitatively. We found 80 dilemmas experienced in three different arenas (food situations at school, meals at home, meals outside) and characterized lived experiences of children with CD in everyday life (specific emotions, difficulties in relationships and in management of daily life). Children with CD experience strong emotions related to the GFD, permeating several aspects of everyday life. These dilemmas may be missed by a conventional, questionnaire-based approach to the psycho-social consequences of CD treatment. PMID- 24225847 TI - Stable Cu nanoclusters: from an aggregation-induced emission mechanism to biosensing and catalytic applications. AB - Highly luminescent and stable Cu nanoclusters (NCs) have been prepared, displaying an intriguing aggregation-induced emission (AIE) feature. The attractive AIE feature allowed the CuNCs to serve as pH stimuli-responsive functional materials. Additionally, we explored the utility of CuNCs for biosensing and catalysis applications. PMID- 24225848 TI - Chiral bis(phthalocyaninato) yttrium double-decker complexes. Synthesis, structure, spectroscopy, and electrochemistry. AB - Two new chiral sandwich-type bis(phthalocyaninato) yttrium double-decker complexes including the homoleptic species (R)- and (S)-Y[Pc(OBNP)4]2 (1) and a heteroleptic analogue (R)- and (S)-Y(Pc)[Pc(OBNP)4] (2) {Pc = unsubstituted phthalocyaninate; [Pc(OBNP)4] = tetrakis(dinaphtho[1,2-e:1',2'-g]-1,4 (dioxocine)[2,3-b;2',3'-k;2'',3''-t;2''',3'''-c']phthalocyaninate)} have been synthesized and spectroscopically characterized. In particular, the molecular structures of (R)- and (S)-1 were determined on the basis of single crystal X-ray diffraction analysis, representing the first structurally characterized chiral bis(phthalocyaninato) rare earth double-decker complexes. Perfect mirror-image CD signals observed in the whole phthalocyanine absorption range of the CD spectra of the (R)- and (S)-enantiomers for both compounds reveal the effective chiral information transfer from the peripheral binaphthyl moieties to the phthalocyanine chromophore, while the difference observed in the CD spectrum between 1 and 2 indicates the effect of the chiral substituent number on the chiral information transfer. Nevertheless, the absolute structures unambiguously elucidated for both enantiomers of the homoleptic double-decker render it possible to clarify the chirality of optically active bis(phthalocyaninato) rare earth compounds. PMID- 24225849 TI - One-step electrochemical fabrication of nanoporous gold wire arrays from ionic liquid. AB - Nanoporous gold wire arrays were fabricated by a simple and straightforward template-free method from ionic liquid. The electrodeposition of AuZn nanowires was coupled with the galvanic metal displacement of the zinc in the wires by gold, creating the final nanoporous gold wire arrays. PMID- 24225850 TI - HIV provides ample PAMPs for innate immune sensing. PMID- 24225851 TI - Chronic arsenic exposure and microbial drug resistance. PMID- 24225852 TI - Pathogen selection drives nonoverlapping associations between HLA loci. AB - Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host-pathogen systems. PMID- 24225853 TI - More players in the plant unfolded response. PMID- 24225855 TI - Editor's note. PMID- 24225854 TI - Fine-scale variation in meiotic recombination in Mimulus inferred from population shotgun sequencing. AB - Meiotic recombination rates can vary widely across genomes, with hotspots of intense activity interspersed among cold regions. In yeast, hotspots tend to occur in promoter regions of genes, whereas in humans and mice, hotspots are largely defined by binding sites of the positive-regulatory domain zinc finger protein 9. To investigate the detailed recombination pattern in a flowering plant, we use shotgun resequencing of a wild population of the monkeyflower Mimulus guttatus to precisely locate over 400,000 boundaries of historic crossovers or gene conversion tracts. Their distribution defines some 13,000 hotspots of varying strengths, interspersed with cold regions of undetectably low recombination. Average recombination rates peak near starts of genes and fall off sharply, exhibiting polarity. Within genes, recombination tracts are more likely to terminate in exons than in introns. The general pattern is similar to that observed in yeast, as well as in positive-regulatory domain zinc finger protein 9 knockout mice, suggesting that recombination initiation described here in Mimulus may reflect ancient and conserved eukaryotic mechanisms. PMID- 24225856 TI - Medical crisis counseling: A new service delivery model. AB - The diagnosis or exacerbation of a chronic illness, the aftermath of a serious accident, or worries about future in the context of illness or debilitating injury are all examples of medical crises that pose significant coping challenges. Too often, traditional approaches to psychotherapy have been unable to respond the most urgent needs of people confronting such crises. Medical crisis counseling is a specialized approach to addressing the needs of individuals and families confronted by the difficulties of coping with losses or changes, as well as the challenge of living with long-term illness. This paper describes the medical crisis counseling model in contrast with other more traditional intervention approaches. PMID- 24225857 TI - Within-family reproductive technologies as a solution to childlessness due to infertility: Psychological issues and interventions. AB - Patients choosing new reproductive technologies benefit from psychological consultation as they face unforeseen emotional and interpersonal sequalae from these procedures. This paper focuses on those patients who choose family members or close friends (i.e., "known donors") to donate sperm or eggs or uteri in order to conceive and produce their babies. Medical family therapy offers these patients and families a framework from which to examine the biological, psychological, and interpersonal issues involved in these within-family solutions to childlessness due to infertility. PMID- 24225858 TI - Family management of childhood diabetes. AB - This paper reviews the available literature on family management of childhood diabetes and highlights gaps in the current knowledge base. Four aspects of family management of childhood diabetes are discussed: coping (how the family adjusts to living with a child who has diabetes), compliance (how the family manages the child's diabetes on a daily basis), communication (how the family learns from interactions with the health provider), and context (how the family environment "sets the stage" for managing diabetes). PMID- 24225859 TI - Couples coping with cancer: Research issues and recent findings. AB - The diagnosis of cancer in one partner can impose numerous changes for both the individual diagnosed with cancer and his or her healthy spouse. In this article, the literature on spouse social support in the context of cancer is reviewed. The importance of understanding support given and received within a close relationship using an interactional, contextual perspective is emphasized. Examining support-related interactions and understanding the personal characteristics that determine the type and amount of support that providers give and the kind of support individuals prefer, and investigating why significant others respond in supportive or critical ways is important. In addition, the study of support interactions must be placed in the both in the context of a marriage and in the context of a catastrophic life event such as cancer. A longitudinal study of patients with gastrointestinal cancer and their healthy partners was undertaken to examine these issues, and the design of this study is described. General problems conducting research with couples undergoing a severe life stressor as well as specific problems our research group has encountered while setting up a research program in the cancer setting are reviewed. PMID- 24225860 TI - Psychological impact of breast cancer on the patient and the family: A clinical perspective. AB - Breast cancer is the most frequently occurring cancer in women, with 182,000 new cases diagnosed in 1993. Breast cancer will strike a sizable percentage of women during the child-rearing years impacting, therefore, not only on the woman, but on the significant others in her life. This article explores the impact of breast cancer for the patient's life partner, parents, and children. A model intervention program for cancer patients with young children, piloted at the Derner Institute and developed in conjunction with the American Cancer Society, is also discussed. PMID- 24225862 TI - Treatment of urethral catheter dependence: A case study of intervention in the interdisciplinary geriatric setting. AB - This case report describes the assessment and treatment of a 69-year-old male medical patient with urethral catheter dependence. Assessment revealed an anxiety/phobic component to the dependence and hypothesized detrusor muscle deconditioning. Retraining of the bladder and desensitization to the anxiety provoking situation were achieved by exposure to decatheterization in the context of a supportive adult day health care setting. Interdisciplinary collaboration between nursing and psychology were associated with successful functional, social, and psychological outcomes. PMID- 24225861 TI - Adult urinary incontinence: Assessment, intervention, and the role of clinical health psychology in program development. AB - Urinary incontinence (UI) is a disorder receiving little attention from clinical health psychologists. This paper establishes the importance of addressing the issue of UI within the clinical and research practices of clinical health psychologists. Over 10 million Americans suffer from loss of bladder control. Incontinence affects over half of older individuals in long-term care institutions, about one-third of hospitalized elderly, and up to 30% of Americans over the age of 60 living at home. Because of social stigma and misconceptions attached to urinary incontinence, it is estimated that less than half of those affected see a physician about their condition. Since UI is generally associated with medical, social, psychological, and economic consequences, a multidisciplinary perspective is important because these factors are integral in the selection of appropriate treatment. Definitions of UI, its incidence and costs, and brief reviews of treatment and management techniques are presented. Psychological sequelae and treatments are presented as a foundation for developing further treatment and research approaches. Guidelines for collaboration and consultation by clinical health psychologists with medical professionals in the area of UI are also discussed. PMID- 24225863 TI - Neurobehavioral deficits, adolescent traumatic brain injury, and transition to college. AB - Outcome following traumatic brain injury (TBI) has been frequently evaluated for adults, although there has been minimal research on adolescents with TBI. It has been argued that TBI sequelae may be more difficult for adolescents to adjust to given developmental changes in physical (puberty), interpersonal (self-concept), and environmental domains (transition to college). In addition, it is commonly acknowledged that moderator variables such as psychiatric history, family functioning, substance use, and sexuality impact functional outcome following TBI, although it is often difficult to objectively evaluate these variables. The current study examined relationships among TBI-related deficits, moderator variables, and academic outcomes for six adolescents transitioning to college. The findings suggest that it may not be appropriate to predict functional outcome based solely on objective neuropsychological results. However, moderator variables appear to have a more direct relationship with outcome, depending on the moderator variable and the individual. PMID- 24225864 TI - Relationship between the Millon Behavioral Health Inventory and the minnesota multiphasic personality inventory (MMPI) in low-back pain patients. AB - The Millon Behavioral Health Inventory (MBHI) is being used with increasing frequency for the assessment of chronic pain, although there is a relative lack of evidence as to its utility, and prior studies have not examined low back pain. This investigation compared the MBHI to the MMPI in a sample of low-back pain patients and analyzed subgroups of pain patients based upon their MBHI responses. Subjects were 60 patients who had been admitted to outpatient multidisciplinary pain clinics of two Chicago-area hospitals. Patients completed both the MMPI and the MBHI and provided demographic information. Results of correlational analyses indicated strong relationships between the MBHI psychogenic attitude, psychosomatic correlate, and prognostic index scales and the validity scales of the MMPI. The MBHI Pain Treatment Responsivity scale (PP) correlated with 16 of the other 19 MBHI scales. PP did not demonstrate specificity with low back pain patients. The results of both the scale comparisons and the exploratory two-group cluster subgroup analysis support the notion that responses to the MBHI are largely affected by the respondent's tendency to deny psychopathology or to admit emotional distress. PMID- 24225865 TI - Correlation of photosystem-II complexes with exoplasmatic freeze-fracture particles of thylakoids of the cyanobacterium Synechococcus sp. AB - The supramolecular structure of the exoplasmic freeze-fracture particles of thylakoids of the thermophilic cyanobacterium Synechococcus sp. is compared with that of isolated photosystem-II complexes. The in-situ EF particles are scattered on the thylakoids or organized in rows of variable length; the latter aligned particles measure 10 nmx20 nm and are separated perpendicular to their long axis into two parts. We propose that they represent dimers composed of two monomeric 10-nm EF particles side by side. Isolated photosystem (PS)II particles correspond in size to the monomeric 10-nm EF particles as analysed by negative contrast and freeze-fracture electron microscopy. Dimeric PSII particles, very similar to the in-situ 10 nmx20 nm EF particles, are obtained after incorporation of purified PSII complexes into liposomes made from phospholipid and cholesterol. Each monomeric complex consists of the reaction center, the water-splitting system, the chlorophyll antennae and phycobilisome-binding polypeptides. We propose that the dimeric complexes bind one hemidiscoidal phycobilisome at their domains exposed to the external side of the thylakoids. The implications of this arrangement of the PSII-phycobilisome complexes within the thylakoids upon excitation-energy distribution are discussed. PMID- 24225866 TI - The release of alpha-amylase through gibberellin-treated barley aleurone cell walls : An immunocytochemical study with Lowicryl K4M. AB - Localisation of alpha-amylase (EC 3.2.1.1.) in low-temperature-embedded isolated barley (Hordeum vulgare L.) aleurone has been achieved using rhodamine-labelled secondary antibodies and the protein A-gold technique. Treatment with gibberellic acid (GA3) resulted in an increase of immunofluorescence in the cytoplasm of aleurone cells and also its appearance in specific regions of the cell walls. Cytoplasmic label was neither perinuclear nor associated specifically with aleurone grains as had been found in earlier work, but was present throughout the cytoplasm of all cells. A relatively high level of labelling occurred in hydrolysed wall regions. Label was also associated with plasmodesmata in both hydrolysed and unhydrolysed wall regions. The pattern of labelling indicates that alpha-amylase is released from aleurone via digested wall channels and that, except for the inner wall layer, unhydrolysed regions are impermeable to the enzyme. It is suggested that the resistant wall tubes around plasmodesmata may facilitate enzyme release by providing a pathway for transfer, especially of wall hydrolases, into the more impermeable parts of the wall. PMID- 24225867 TI - Cellular compartmentation of ureide biogenesis in root nodules of cowpea (Vigna unguiculata (L.) Walp.). AB - Cowpea (Vigna unguiculata (L.) Walp.) nodules have been investigated by means of cytochemical and immunocytochemical procedures at the ultrastructural level in order to assess the role of the uninfected cells in ureide biogenesis. Uricase activity in the nodules was shown by cytochemical methods to be localized exclusively in the numberous large peroxisomes confined to the uninfected cells; the small peroxisomes in the infected cells did not stain for uricase. Uricase was also localized in the peroxisomes of uninfected cells by immunogold techniques employing polyclonal antibodies against nodule-specific uricase of soybean. There was no labeling above background of any structures in the infected cells. The results indicate that the uninfected cells are essential for ureide biogenesis in cowpea. Although tubular endoplasmic reticulum, the presumptive site of allantoinase, increases greatly in the uninfected cells during nodule development, it virtually disappears as the nodules mature. The inconsistency between the disappearance of the tubular endoplasmic reticulum from older nodules and the high allantoinase activity reported for older plants remains to be explained. PMID- 24225868 TI - Ultrastructure of the salt glands of the mangrove, Avicennia marina (Forssk.) Vierh., as indicated by the use of selective membrane staining. AB - Each salt-excreting gland of the mangrove Avicennia marina (Forsskal) Vierh. consists of two to four collecting cells, one stalk cell, and eight to twelve excretory cells. Differential membrane staining by zinc iodide-osmium tetroxide (as a post-fixative) or phosphotungstic acid (as a section-stain) was used to characterise the ultrastructure of the glands. A large amount of tubular endoplasmic reticulum was found in the stalk and excretory cells of the gland, but not in the collecting cells. The ultrastructural arrangement of the endoplasmic reticulum indicates that salt is loaded from the apoplasm into the endoplasmic reticulum of the symplasm at the base of the stalk cell, traverses both cell types in the endoplasmic reticulum, and is excreted at the outer edge of the gland by an eccrine-type mechanism. Increasing development of the tubular endoplasmic reticulum accompanied differentiation of the gland cells. PMID- 24225869 TI - Elicitor induction of the synthesis of a novel lectin-like arabinosylated hydroxyproline-rich glycoprotein in suspension cultures of Phaseolus vulgaris L. AB - A novel lectin-like glycoprotein which accumulates in response to fungal elicitor action has been characterised in endomembranes from suspension cultures of French bean (Phaseolus vulgaris L.). The lectin, which has specificity towards N acetylglucosamine oligomers, consists of a polypeptide of apparent molecular weight (Mr) 31 000 which is rich in glycine and contains 6.7% hydroxyproline O linked to arabinose-containing oligosaccharides to give a glycoprotein of Mr 42500. A dual-labelling technique has been used to identify changes in the synthesis of the glycoprotein in cells exposed to fungal elicitor molecules. Thus, incorporation of [(14)C]proline into membranes in vivo and of [1( 3)H]arabinose from uridine 5'-diphosphate [1(-3)H]arabinose in vitro and analysis by isoelectric focussing-polyacrylamide gel electrophoresis gave absolute correspondence of the labelled isoform of the glycoprotein. Having established the absence of contaminating polypeptides, subsequent analysis of microsomal fractions bysodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the peak of sythesis of the Mr-42500 glycoprotein occurred 4 h after the addition of fungal elicitor. The changes in the level of incorporation into the glycoprotein monomers were concomitant with increases in the activity of prolyl hydroxylase (EC 1.14.11.2)Incorporation of [(14)C]proline and its subsequent post translational modification to hydroxyproline in microsomal polypeptides was followed by rapid transfer into the wall with an average t 1/2 of about 7 min. The Mr-42500 glycoprotein was rapidly transferred out of the endomembrane fraction with a t 1/2 of 2 min and could be detected in wall fractions where it became progressively less extractable. The glycoprotein, which clearly differs from bean extensin, accounts for up to 40% of the hydroxyproline newly exported in response to elicitor action. The lectin, which resembles those found in the Solanaceae and which is coinduced with enzymes of phytoalexin synthesis, may play some role in disease resistance. PMID- 24225870 TI - Model systems for the immunolocalisation of cis, trans abscisic acid in plant tissues. AB - To explore the feasibility of immunolocalisation of endogenous abscisic acid (ABA), model systems were developed for testing quantitatively the sensitivity of the second antibody peroxidase/antiperoxidse (PAP) method for immunolocalisation of ABA on plant tissues. Exogenous (+/-)ABA was fixed to carrot sections on glass slides or to homogenised pea cotyledon material on microtitre plates, either directly by carbodiimide fixation or by glutaraldehyde fixation of ABA-protein conjugates linked through the C1 carboxyl by 1-ethyl-3(3-dimethyl-amino-propyl) carbodiimide hydrochloride (EDC). Backgrounds were decreased by including 0.1% normal goat serum in the incubations, by including 0.1% Triton X-100 as a wetter, by including glycine in the rinses after EDC fixation and by using low-pH rinses after incubation with the primary antibody. Serum antibodies recognising the peptide bond between the protein and abscisic acid were removed by preincubating the serum with acetic acid conjugated to protein. Positives were only accepted when they could be eliminated by adding an excess of ABA-protein conjugate in the primary antiserum. By using a soluble peroxidase reaction product to facilitate quantitation, the limit of reliable exogenous ABA detection was found to be only of the order of 1 pmol. For the histochemical immunolocalisation of endogenous ABA, better antisera and lower backgrounds will be required.The efficiency of fixation of exogenous ABA was determined using [(3)H] or [(14)C]ABA. When aqueous EDC or di-isopropyl carbodiimide (IPC) were used the fixation efficiency was low (up to 5%), but much higher efficiencies (up to 80%) were obtained using IPC vapour with freeze-dried material. Similarly efficient fixation of endogenous ABA in pea cotyledon material, as determined by gas chromatography-mass spectrometry analysis, was obtained using the same technique. The PAP method failed to detect fixed endogenous ABA in pea cotyledons, even though the total tissue amounts present exceeded 1 pmol, evidence that not enough of the ABA was accessible to the antibody. PMID- 24225871 TI - Effects of aluminum on the release and-or immobilization of soluble phosphate in corn root tissue : A (31)P-nuclear magnetic resonance study. AB - The effects of aluminum ions on the generation of mobile inorganic phosphate (Pi) within the cells of excised maize (Zea mays L.) root tips were examined using (31)P-nuclear magnetic resonance ((31)P-NMR) spectroscopy. When perfused with a solution containing 50 mM glucose and 0.1-5.0 mM Ca(2+) at pH 4.0, 3-5-mm-long excised maize root tips from 3-d-old seedlings showed a significant (approx. 100%) increase in the amount of mobile Pi, (primarily vacuolar) over a period of 30 h. This increase was above that which can be accounted for by the hydrolysis of endogenous sugar phosphates and nucleotides. A change of the pH of the perfusion solution to 7.0 reduced the increase in Pi to approx. 50%. Omission of Ca(2+) in the solution at pH 4.0 caused the mobile Pi to increase to about 170%. However, the presence of Al(3+) or both Ca(2+) and Al(3+) in the solution resulted in a significant loss (35-50%) of mostly vacuolar Pi over the same period of time. When root tips containing up to 65% of newly released Pi, produced after 20 h perfusion, were exposed to Al(3+), no additional increase in the level of the mobile-Pi signal area was noted. Exposure to Al(3+) with Ca(2+) and glucose under hypoxia at pH 4.0 resulted in a threefold decrease in intracellular Pi content after the root tips were returned to aerobic conditions. These results indicate that external pH plays an important role in the generation of mobile intracellular Pi and that the presence of both Ca(2+) and Al(3+) can independently suppress the production of this excess Pi and ultimately reduce the vacuolar Pi. PMID- 24225872 TI - Energy relations of solute loading in sieve elements of willow. AB - Experiments are described which attempt to clarify the quantitative relationship between sieve-tube loading of sucrose, and ATP-turnover rates in the phloem of willow (Salix viminalis L.). Two experimental approaches have been made towards the solution of this problem. In the first of these the respiratory breakdown of (14)C-sugars was measured in segments of willow stem when no sieve-tube transport was taking place, and also under conditions where transport was occurring in response to the feeding of individuals of the aphid Tuberolachnus salignus (Gmelin). An increase in respiratory activity, measured by the output of (14)CO2, was found to occur as a consequence of transport. Since the rate of sieve-tube sugar loading could be measured by the production of honeydew from the aphids, and by making assumptions concerning the production of ATP in respiration, it was concluded that the stoichiometry of sucrose loading was 1.9 mol ATP . (mol sucrose)(-1). A somewhat higher value of 2.5 mol ATP . (mol sucrose)(-1) was found using the second approach. In this, attempts were made to measure ATP turnover rates using [(32)P]orthophosphate supplied to strips of willow bark which bore exuding aphid stylets. PMID- 24225873 TI - Reassimilation of carbon dioxide by Flaveria (Asteraceae) species representing different types of photosynthesis. AB - The capability to reassimilate CO2 originating from intracellular decarboxylating processes connected with the photorespiratory glycolate pathway and-or decarboxylation of C4 acids during C4 photosynthesis has been investigated with four species of the genus Flaveria (Asteraceae). The C3-C4 intermediate species F. pubescens and F. anomala reassimilated CO2 much more efficiently than the C3 species F. cronquistii and, with respect to this feature, behaved similarly to the C4 species F. trinervia. Therefore, under atmospheric conditions the intermediate species photorespired with rates only between 10-20% of that measured with F. cronquistii. At low oxygen concentrations (1,5%) the reassimilation potential of F. anomala approached that of F. trinervia and was distinct from that found with F. pubescens. The data are discussed with respect to a possible sequence of events during evolution of C4 photosynthesis. If compared with related data for C3-C4 intermediate species from other genera they support the hypothesis that, during evolution of C4 photosynthesis, an efficient capacity for CO2 reassimilation evolved prior to a CO2-concentrating mechanism. PMID- 24225874 TI - Phytochrome action in light-grown mustard: kinetics, fluence-rate compensation and ecological significance. AB - Internode extension in young, light-grown mustard plants was measured continuously to a high degree of resolution using linear voltage displacement transducers. Plants were grown in background white light (WL) and the first internode was irradiated with supplementary far-red (FR) from fibre-optic light guides, depressing the Pfr/P (ratio of FR-absorbing form of phytochrome to total spectrophotometrically assayable phytochrome) within the internode and causing an acceleration of extension rate. The internode was sensitive to periods of FR as brief as 1 min, with a sharp increase in extension rate occurring after the return to background WL only. The mean latent period of the response to FR was approx. 10 min. Periods of FR longer than approx. 35 min caused an apparently biphasic growth response, with an initial sharp acceleration in extension rate (Phase 1) being followed by a brief deceleration and a further acceleration to a more-or-less steady elevated rate, somewhat less than the first peak (Phase 2). With such longer-term FR, extension rate decelerated upon FR switch-off after a mean lag of approx. 6 min, achieving the prestimulation extension rate within 16 min. The magnitude of the FR-induced increase in extension rate, expressed as a percentage of the rate in WL alone, was an inverse, linear function of the phytochrome photoequilibrium (i.e. Pfr/P, measured in etiolated test material irradiated under the same geometry) over the range 0.17 to 0.63. This relationship was not significantly affected by variations in backround WL fluence rate over the range 50-150 MUmol.m(-2).s(-1) and was held both for Phase 1 and Phase 2 of the response. The data provide evidence for rapid coupling/uncoupling between phytochrome and its transduction chain in the light-grown plant and for fluence-rate compensation of the regulation of extension rate. The extensive linearity of the relationship between phytochrome photoequilibrium and proportional extension rate increment allows for fine tuning in shade avoidance. The results are discussed with respect to recent evidence on the nature of phytochrome in light-grown plants and in relation to the function of phytochrome in plants growing in the natural environment. PMID- 24225875 TI - Implication of tyramine in the biosynthesis of morphinan alkaloids in Papaver. AB - Doubly-labeled [(3)H, (14)C]tyrosines, [1-(13)C-]tyramine or [2-(14)C]tyramine, administered to the stems of intact Papaver somniferum L. plants, were found to be incorporated into the morphinan alkaloids of the plant with comparable efficiency. (3)H/(14)C ratios of alkaloids from plants fed the tyrosines were consistent with an almost equal conversion of this amino acid into the tetrahydroisoquinoline (TIQ) and benzyl-derived segments. Nuclear magnetic resonance (NMR) analyses of morphine isolated after administration of [1 (13)C]tyramine demonstrated selective labeling of C-16 of the alkaloid, indicating the conversion of this amine primarily into the TIQ-derived moiety. Morphine and thebaine labeled by [2-(14)C]tyramine were degraded to phenanthridines and N,N'-dimethyl ethylamines. Of the total radioactivity in the alkaloids 97% was found to be associated with the ethylamines, a distribution consistent with the NMR data. This preferential utilization of tyramine in the biosynthesis of morphinan alkaloids can be explained by the compartmentalization of intermediates and enzymes of the pathway. PMID- 24225876 TI - Cell-suspension culture of Arachis hypogaea L.: model system of specific enzyme induction in secondary metabolism. AB - A peanut (Arachis hypogaea L.) cell-suspension culture susceptible to selective induction of stilbene formation was established. The principles of defense responses of the whole plant were found to be retained in the artificial system. The suspension culture was characterized by its growth curve and by various biochemical parameters. In the stationary phase, reached 8 d after transfer to a new medium, the formation of stilbenes and stilbene synthase could be induced without altering the levels of other enzymes. Eighteen hours after applying an artificial elicitor (ultraviolet-C light) or 4 h after eliciting with a crude preparation of Phytophthora cambivora cell walls, phenylalanineammonia-lyase activity was increased eightfold and stilbene-synthase activity 20-fold. The activity of phenylalanine ammonia-lyase reached its peak at a slightly different time from that of stilbene synthase. The main products of L-phenylalanine metabolism in the induced cells were resveratrol, 3,3',5-trihydroxy-4' methoxystilbene and isopentenylresveratrol. Likewise, feruloyl-CoA reductase, as a parameter of lignin formation, was enhanced following induction, albeit with a different time course and with a less steep increase than found for phenylalanine ammonia-lyase and stilbene synthase. PMID- 24225877 TI - Embryogenic callus formation from maize protoplasts. AB - Maize (Zea mays L.) protoplasts have been obtained which divide rapidly and produce a callus that differentiates to form somatic embryos. The somatic embryos can be induced to form roots and small leaf-like structures. The genotype was the hybrid A188xBlack Mexican Sweet. Protoplasts were prepared from an embryogenic suspension culture derived from a Type II callus which had been selected from Type I callus produced by immature zygotic embryos. The basal medium for the suspension culture was N6 (C.C. Chu et al., 1975, Scientia Sinica 18, 659-668). The 2,4-dichlorophenoxyacetic acid concentration of the suspension culture was critical for subsequent protoplast growth and was optimal at 4.0 mg.l. Protoplasts had to be cultured in a low-osmoticum medium (0.3 M mannitol) for subsequent cell divisions to occur. The protoplasts have been transformed transiently with the gene chloramphenicol acetyltransferase (CAT) containing the 35S promoter obtained from cauliflower mosaic virus (CaMV-35S). PMID- 24225878 TI - Oryzalin, a dinitroaniline herbicide, binds to plant tubulin and inhibits microtubule polymerization in vitro. AB - The effects of oryzalin, a dinitroaniline herbicide, on chromosome behavior and on cellular microtubules (MTs) were examined by light microscopy and immunogold staining, respectively, in endosperm cells from Haemanthus katherinae Bak. Brief treatments with 1.0.10(-8) M oryzalin reduced markedly the migration rate of anaphase chromosomes and 1.0.10(-7) M oryzalin stopped migration abruptly. Oryzalin (1.0.10(-7) M) depolymerized MTs and prevented the polymerization of new MTs at all stages of the mitotic cycle. The chromosome condensation cycle was unaffected by oryzalin. Endothelial cells from the heart of Xenopus leavis showed no chromosomal or microtubular rearrangements after oryzalin treatment. The inhibition by oryzalin of the polymerization of tubulin isolated from cultured cells of Rosa sp. cv. Paul's scarlet was examined in vitro by turbidimetry, electron microscopy and polymer sedimentation analysis. Oryzalin inhibited the rapid phase of taxol-induced polymerization of rose MTs at 24 degrees C with an apparent inhibition constant (K i ) of 2.59.10(6) M. Shorter and fewer MTs were formed with increasing oryzalin concentrations, and maximum inhibition of taxol induced polymerization occurred at approx. 1:1 molar ratios of oryzalin and tubulin. Oryzalin partially depolymerized taxol-stabilized rose MTs. Ligand binding experiments with [(14)C]oryzalin demonstrated the formation of a tubulin oryzalin complex that was time- and pH-dependent. The tubulin-oryzalin interaction (24 degrees C, pH 7.1) had an apparent affinity constant (K app) of 1.19.10(5) M(-1). Oryzalin did not inhibit taxol-induced polymerization of bovinebrain MTs and no appreciable binding of oryzalin to brain tubulin or other proteins was detected. The results demonstrate pharmacological differences between plant and animal tubulins and indicate that the most sensitive mode of action of the dinitroaniline herbicides is the direct poisoning of MT dynamics in cells of higher plants. PMID- 24225879 TI - Calcium transport by pea root membranes : I. Purification of membranes and characteristics of uptake. AB - Calcium transport has been studied using purified endomembrane vesicles from dark grown roots of Pisum sativum L. Membranes from a mixed microsomal (non mitochondrial) fraction showed ATP-dependent calcium uptake which was released by the ionophore A 23187, had a pH optimum of 7.2 and required Mg(2+) for uptake. Membranes were further purified using a rapid sucrosedensity-gradient technique yielding vesicles suitable for transport studies, and were identified using marker enzymes. Uptake by plasma membrane, tonoplast, endoplasmic reticulum and Golgi apparatus was indicated. Uptake by membranes of low density (predominantly tonoplast) had a pH optimum of 7.2-7.4 and nucleotide specificity ATP> guanosine 5'-triphosphate>inosine 5'-triphosphate>ADP>, while that by high-density membranes had a pH optimum of 7.5-7.9 and less specificity for ATP. The importance of regulating sucrose concentrations in calcium transport studies was demonstrated. PMID- 24225880 TI - Calcium transport by pea root membranes : II. Effects of calmodulin and inhibitors. AB - Calcium transport by purified endomembrane vesicles from roots of Pisum sativum L. was studied. Two types of ATP-dependent transport were demonstrated, protonophore-sensitive calcium/proton antiport and protonophore-insensitive transport. The former was predominantly located in the tonoplast, while the latter was associated with the plasma membrane and Golgi apparatus. Calcium uptake by membranes of low buoyant density (tonoplast) was inhibited by nitrate and was not sensitive to sodium orthovanadate while that by membranes of high buoyant density (plasma membrane, Golgi apparatus) was inhibited by sodium orthovanadate and insensitive to nitrate. Endoplasmic reticulum also took up calcium in the presence of ATP; however, because of its imperfect separation from the tonoplast, the nature of the calcium-transport system present could not be fully characterised. None of the calcium transporters were stimulated by calmodulin or inhibited by calmodulin inhibitors. PMID- 24225881 TI - Gibberellins and the procera mutant of tomato. AB - The procera mutant of tomato (Lycopersicon esculentum L.) has a phenotype which is remarkably similar to that of normal tomatoes treated with exogenous gibberellin (GA), indicating that it might be a GA over-producer. However, analysis of endogenous GAs by gas chromatography-mass spectrometry showed that Procera actually has lower levels of GA20 and GA1 than normal. The reason for these anomalously low GA levels is not clear, as there was no difference between procera and normal plants in their ability to metabolize [(3)H]GA20. The procera mutant responded to exogenous gibberellic acid with increased extension growth, but the proportional response for a given dose of GA was the same in procera and normal plants. It therefore appears that the procera mutation does not directly affect either the GA status of the plant, or its ability to respond to GA. PMID- 24225882 TI - In-vitro auxin transport in membrane vesicles from maize coleoptiles. AB - When membrane vesicles from maize (Zea mays L.) coleoptiles are extracted at high buffer strength, a pH-driven, saturable association of [(14)C] indole-3-acetic acid is found, similar to the in-vitro auxin-transport system previously described for Cucurbita hypocotyls. The phytotropins naphthylphthalamic acid and pyrenoylbenzoic acid increase net uptake, pressumably by inhibiting the auxin efflux carrier. PMID- 24225883 TI - Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes. AB - The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of beta-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, we investigated the role of galectin-3 during the invasion and intracellular trafficking of T. cruzi extracellular amastigotes (EAs). Endogenous galectin-3 from mouse peritoneal macrophages accumulated around the pathogen during cell invasion by EAs. In addition, galectin-3 accumulated around parasites after their escape from the parasitophorous vacuole. Thus, galectin-3 behaved as a novel marker of phagolysosome lysis during the infection of host cells by T. cruzi. PMID- 24225885 TI - I don't know the question, but sex is definitely the answer! Focus on "In pursuit of scientific excellence: sex matters" and "Do you know the sex of your cells?". PMID- 24225884 TI - Cellular calcium dynamics in lactation and breast cancer: from physiology to pathology. AB - Breast cancer is the second leading cause of cancer mortality in women, estimated at nearly 40,000 deaths and more than 230,000 new cases diagnosed in the U.S. this year alone. One of the defining characteristics of breast cancer is the radiographic presence of microcalcifications. These palpable mineral precipitates are commonly found in the breast after formation of a tumor. Since free Ca(2+) plays a crucial role as a second messenger inside cells, we hypothesize that these chelated precipitates may be a result of dysregulated Ca(2+) secretion associated with tumorigenesis. Transient and sustained elevations of intracellular Ca(2+) regulate cell proliferation, apoptosis and cell migration, and offer numerous therapeutic possibilities in controlling tumor growth and metastasis. During lactation, a developmentally determined program of gene expression controls the massive transcellular mobilization of Ca(2+) from the blood into milk by the coordinated action of calcium transporters, including pumps, channels, sensors and buffers, in a functional module that we term CALTRANS. Here we assess the evidence implicating genes that regulate free and buffered Ca(2+) in normal breast epithelium and cancer cells and discuss mechanisms that are likely to contribute to the pathological characteristics of breast cancer. PMID- 24225887 TI - Isotopic signatures of N2O produced by ammonia-oxidizing archaea from soils. AB - N2O gas is involved in global warming and ozone depletion. The major sources of N2O are soil microbial processes. Anthropogenic inputs into the nitrogen cycle have exacerbated these microbial processes, including nitrification. Ammonia oxidizing archaea (AOA) are major members of the pool of soil ammonia-oxidizing microorganisms. This study investigated the isotopic signatures of N2O produced by soil AOA and associated N2O production processes. All five AOA strains (I.1a, I.1a-associated and I.1b clades of Thaumarchaeota) from soil produced N2O and their yields were comparable to those of ammonia-oxidizing bacteria (AOB). The levels of site preference (SP), delta(15)N(bulk) and delta(18)O -N2O of soil AOA strains were 13-30%, -13 to -35% and 22-36%, respectively, and strains MY1-3 and other soil AOA strains had distinct isotopic signatures. A (15)N-NH4(+)-labeling experiment indicated that N2O originated from two different production pathways (that is, ammonia oxidation and nitrifier denitrification), which suggests that the isotopic signatures of N2O from AOA may be attributable to the relative contributions of these two processes. The highest N2O production yield and lowest site preference of acidophilic strain CS may be related to enhanced nitrifier denitrification for detoxifying nitrite. Previously, it was not possible to detect N2O from soil AOA because of similarities between its isotopic signatures and those from AOB. Given the predominance of AOA over AOB in most soils, a significant proportion of the total N2O emissions from soil nitrification may be attributable to AOA. PMID- 24225886 TI - Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms. AB - An unusual symbiosis, first observed at ~3000 m depth in the Monterey Submarine Canyon, involves gutless marine polychaetes of the genus Osedax and intracellular endosymbionts belonging to the order Oceanospirillales. Ecologically, these worms and their microbial symbionts have a substantial role in the cycling of carbon from deep-sea whale fall carcasses. Microheterogeneity exists among the Osedax symbionts examined so far, and in the present study the genomes of the two dominant symbionts, Rs1 and Rs2, were sequenced. The genomes revealed heterotrophic versatility in carbon, phosphate and iron uptake, strategies for intracellular survival, evidence for an independent existence, and numerous potential virulence capabilities. The presence of specific permeases and peptidases (of glycine, proline and hydroxyproline), and numerous peptide transporters, suggests the use of degraded proteins, likely originating from collagenous bone matter, by the Osedax symbionts. (13)C tracer experiments confirmed the assimilation of glycine/proline, as well as monosaccharides, by Osedax. The Rs1 and Rs2 symbionts are genomically distinct in carbon and sulfur metabolism, respiration, and cell wall composition, among others. Differences between Rs1 and Rs2 and phylogenetic analysis of chemotaxis-related genes within individuals of symbiont Rs1 revealed the influence of the relative age of the whale fall environment and support possible local niche adaptation of 'free living' lifestages. Future genomic examinations of other horizontally-propogated intracellular symbionts will likely enhance our understanding of the contribution of intraspecific symbiont diversity to the ecological diversification of the intact association, as well as the maintenance of host diversity. PMID- 24225888 TI - Ecological succession among iron-oxidizing bacteria. AB - Despite over 125 years of study, the factors that dictate species dominance in neutrophilic iron-oxidizing bacterial (FeOB) communities remain unknown. In a freshwater wetland, we documented a clear ecological succession coupled with niche separation between the helical stalk-forming Gallionellales (for example, Gallionella ferruginea) and tubular sheath-forming Leptothrix ochracea. Changes in the iron-seep community were documented using microscopy and cultivation independent methods. Quantification of Fe-oxyhydroxide morphotypes by light microscopy was coupled with species-specific fluorescent in situ hybridization (FISH) probes using a protocol that minimized background fluorescence caused by the Fe-oxyhydroxides. Together with scanning electron microscopy, these techniques all indicated that Gallionellales dominated during early spring, with L. ochracea becoming more abundant for the remainder of the year. Analysis of tagged pyrosequencing reads of the small subunit ribosomal RNA gene (SSU rRNA) collected during seasonal progression supported a clear Gallionellales to L. ochracea transition, and community structure grouped according to observed dominant FeOB forms. Axis of redundancy analysis of physicochemical parameters collected from iron mats during the season, plotted with FeOB abundance, corroborated several field and microscopy-based observations and uncovered several unanticipated relationships. On the basis of these relationships, we conclude that the ecological niche of the stalk-forming Gallionellales is in waters with low organic carbon and steep redoxclines, and the sheath-forming L. ochracea is abundant in waters that contain high concentrations of complex organic carbon, high Fe and Mn content and gentle redoxclines. Finally, these findings identify a largely unexplored relationship between FeOB and organic carbon. PMID- 24225889 TI - Some physiological aspects of the autecology of the suspension-feeding protozoanTetrahymena pyriformis. AB - Feeding, growth, and reproductive responses of the suspension-feeding protozoanTetrahymena pyriformis to shifts up or down of the density of its bacterial food were observed. The rates of feeding, growth, and reproduction were determined by measuring the rates of uptake of viable bacterial cells, of change of mean volume of the protozoan cells, and of change of number of protozoan cells, respectively. The effects of the nutritional status of the protozoans at the time of shifting were observed also. Results are interpreted in terms of the limited polymorphism exhibited in the life cycle of this organism. Responses in all cases seem to reflect a strategy for exploiting a patchy, transient environment, a conclusion already reached by several earlier investigators. PMID- 24225890 TI - Experimental and modeling studies of a four-trophic level predator-prey system. AB - Experimental studies of a microbial food chain involving organic carbon substrates,Enterobacter aerogenes, and ciliate protozoansParamecium primaurelia andDldinium nasutum were conducted in stirred, aerated batch cultures. Quantitative measurements were made of organic carbon levels and of cell numbers, mean cell volumes, and total biovolumes for all three microbial populations. A mathematical model based on Monod kinetics was developed to describe this four trophic level predator-prey system. The model was formulated in terms of biovolume, which is the product of cell numbers and mean cell size, and includes terms for bio-volume decay. Batch culture data were used to derive parameter values, and model simulations were compared to experimental results. Despite the significance ofParamecium-Didinium studies in ecological literature, the entire food chain has not been previously studied or modeled. PMID- 24225891 TI - Predacity by nematophagous fungi and its relation to the attraction of nematodes. AB - Predacity, the ability of nematophagous fungi to destroy nematodes, was investigated for eight species of fungi by a method using sterilized soil and the nematodePanagrellus redivivus. In addition, the ability of the fungi to attract nematodes was investigated using an agar plate technique. Predacity and attraction were highly correlated (r=0.98) in these tests. The presence of traps in cultures ofArthrobotrys oligospora increased the ability to attract nematodes by a factor of 2. PMID- 24225892 TI - Accumulation and fate of tri-n-butyltin cation in estuarine bacteria. AB - The accumulation and possible metabolic transformation of tri-n-butyltin cation by tin-resistant estuarine bacteria was studied. The bacterial isolates accumulated tributyltin to 3.7-7.7 mg tin per g dry weight of cells by a nonenergy requiring process, probably by adsorption to the cell envelope. Chemical speciation of cell extracts and culture media by combined liquid chromatography-atomic absorption spectrophotometry and tin-selective purge and trap flame photometric gas chromatography for possible tributyltin degradation products revealed no significant biotransformations of tributyltin cation by the tributyltin-resistant isolates. Apparently the isolates accumulate, but do not metabolize tributyltin. PMID- 24225893 TI - Soil microbial counts in relation to site characteristics at a subantarctic Island. AB - Enumerations of colony-forming units of aerobic bacteria and fungi at Marion Island (46 degrees 54'S, 37 degrees 45'E) showed that the mire and bog peats investigated possessed greater numbers of microorganisms on a dry soil weight basis than did the slope fernbrake soils but that counts from both sites were similar per unit soil volume. Afjaeldmark soil of an exposed rocky ridge contained very low microbial populations. Manuring by sea-birds and seals caused an increase in levels of soil N and P and in the numbers of bacteria and fungi. Regression analyses indicated that inorganic N and soil pH explained more of the variation in bacterial and fungal counts respectively than all other soil parameters included in the regression. Variation in botanical composition between the sites was examined using multivariate analysis and the resulting pattern compared with the soil microorganism and nutrient levels. This analysis emphasized the importance of manuring influences in elevating NH4-N and bacterial levels in the soil and allowing the occurrence of a vegetation cover dominated by copriphilous species. No correlation occurred between site botanical factors and soil fungi counts. PMID- 24225894 TI - Mixed continuous culture experiments with an antibiotic-producing streptomycete andEscherichia coli. AB - Four strains ofStreptomyces aureofaciens capable of producing different amounts of tetracycline have been grown in continuous culture with either of two strains ofEscherichia coli orBacillus pumillus. Each of the bacteria had faster specific growth rates than any of the streptomycetes.E. coli NTCT 5993 had a higher affinity for sucrose than didS. aureofaciens SR 11. In mixed culture experiments, the bacteria displaced the streptomycete under the following conditions: (a) when the streptomycete produced no tetracycline; (b) in tetracycline-producing cultures after a fraction of the bacteria had died-the bacterial population that subsequently developed was resistant to the drug; and (c) when using tetracycline resistant bacteria. Under nutrient conditions leading to high antibiotic levels, it was possible to kill all the bacteria, and the streptomycete survived after a transient fall in mycelium and tetracycline levels. No stable mixed population was ever seen. Once tetracycline-resistant bacteria had displaced the streptomycete, and tetracycline concentrations had fallen, a sensitive bacterial population reappeared. Competition between sensitive and resistantE. coli NCTC 5993 in the chemostat confirmed the selective advantage of the sensitive strain. Results were discussed in terms of the role of antibiotics in nature. PMID- 24225895 TI - Background precipitation chemistry monitoring in the Soviet Union. AB - An overview is given of the precipitation chemistry field and laboratory programs of the former U.S.S.R. World Meteorological Organization Background Air Pollution Monitoring Program (WMO BAPMoN). Field and laboratory procedures are discussed, siting criteria are examined, station histories are documented, and four Soviet quality assurance techniques are discussed. Comparison of data from three Soviet BAPMoN stations with data from three U.S. BAPMoN stations indicate that sulfate concentrations are comparable but that U.S. samples are typically much more acidic. Soviet samples tend to have higher concentrations of cations of soil origin and higher concentrations of ammonium. PMID- 24225896 TI - The epiphytic lichen hypogymnia physodes as a biomonitor of atmospheric nitrogen and sulphur deposition in Norway. AB - Hypogymnia physodes was sampled from 179 sites of Scots pine forests regularly distributed throughout Norway. The purpose was to map the nitrogen and sulphur contents of lichen thalli on a large-scale geographical basis, and to relate these values to differences in atmospheric deposition and climate.The lichen nitrogen and sulphur concentrations showed large differences; the highest concentration values being 4-5 times greater than the lowest. The highest nitrogen and sulphur values occurred along the coast of southern Norway and on some sites in the inland of southern Norway. There was a close correlation between the two elements. The lichen N/S ratio decreased with increasing latitude.The nitrogen and sulphur contents ofHypogymnia physodes were both significantly correlated to estimated atmospheric deposition of these two elements in Norway. The degree of explanation improved when climatic variables such as temperature sum, altitude, annual precipitation and temperature were included. Factors promoting growth, such as high bark pH, mild winters, hot summers, high precipitation, high ammonium deposition and high evapotranspiration, were all associated with lower lichen nitrogen and/or sulphur concentrations. Unfavourable growth conditions, such as at high altitude, was related to higher concentrations than expected from deposition models. This indicates that differences in element concentration between nearby localities might be related to local differences in climate and lichen growth conditions. This should be taken into consideration whenever using lichens for biomonitoring. PMID- 24225897 TI - Matrix diffusion effects in the cleanup of heterogeneous aquifers. AB - Simple mathematical models are developed to account for the rather slow mass transport of nonaqueous phase liquid (NAPL) into aqueous solution in groundwater during flushing operations. The models are based on the assumption that this bottleneck in the process is associated with diffusion in the aqueous phase in the porous medium from the location of the NAPL drops/ganglia in a region of relatively low permeability out into a region of substantially higher permeability, somewhat analogous to diffusion from a block of porous rock into a nearby fracture, where the fracture system overwhelmingly dominates the overall permeability. The models include batch flushing, flushing in a laboratory column, and a one-dimensional model for flushing by means of a single recovery well. PMID- 24225898 TI - Using 'found' data to augment a probability sample: Procedure and case study. AB - While probability sampling has the advantage of permitting unbiased population estimates, many past and existing monitoring schemes do not employ probability sampling. We describe and demonstrate a general procedure for augmenting an existing probability sample with data from nonprobability-based surveys ('found' data). The procedure, first proposed by Overton (1990), uses sampling frame attributes to group the probability and found samples into similar subsets. Subsequently, this similarity is assumed to reflect the representativeness of the found sample for the matching subpopulation. Two methods of establishing similarity and producing estimates are described: pseudo-random and calibration. The pseudo-random method is used when the found sample can contribute additional information on variables already measured for the probability sample, thus increasing the effective sample size. The calibration method is used when the found sample contributes information that is unique to the found observations. For either approach, the found sample data yield observations that are treated as a probability sample, and population estimates are made according to a probability estimation protocol. To demonstrate these approaches, we applied them to found and probability samples of stream discharge data for the southeastern US. PMID- 24225900 TI - Novel characteristics of energy spectrum for 3D Dirac oscillator analyzed via Lorentz covariant deformed algebra. AB - We investigate the Lorentz-covariant deformed algebra for Dirac oscillator problem, which is a generalization of Kempf deformed algebra in 3 + 1 dimension of space-time, where Lorentz symmetry are preserved. The energy spectrum of the system is analyzed by taking advantage of the corresponding wave functions with explicit spin state. We obtained entirely new results from our development based on Kempf algebra in comparison to the studies carried out with the non-Lorentz covariant deformed one. A novel result of this research is that the quantized relativistic energy of the system in the presence of minimal length cannot grow indefinitely as quantum number n increases, but converges to a finite value, where c is the speed of light and beta is a parameter that determines the scale of noncommutativity in space. If we consider the fact that the energy levels of ordinary oscillator is equally spaced, which leads to monotonic growth of quantized energy with the increment of n, this result is very interesting. The physical meaning of this consequence is discussed in detail. PMID- 24225899 TI - Expression of CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) by blastic plasmacytoid dendritic cell neoplasms. AB - IMPORTANCE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant neoplasm with cutaneous manifestations and a rapidly progressive clinical course. The diagnosis relies on characteristic clinicopathologic and immunopathologic features. However, the overlap of immunophenotypic features with other cancers, as well as newly discovered interpersonal and intrapersonal phenotypic variations, renders the identification of BPDCN challenging. A greater understanding of the proteins expressed by BPDCN might facilitate its recognition and provide insights into its clinical behavior. OBSERVATIONS: In 7 of 9 patients at 4 tertiary care institutions, immunohistochemical analysis demonstrated strong CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) expression by neoplastic cells. Combined with similar findings observed in 1 former patient, 8 of 10 cases of BPDCN were CD31/PECAM-1 positive. CONCLUSIONS AND RELEVANCE: Expression of CD31/PECAM-1 by BPDCN adds new information about the antigenic profile of this unusual neoplasm. CD31/PECAM-1 influences multiple cell functions including adhesion, apoptosis, coagulation, host response, and protein synthesis that might affect clinical features of BPDCN such as hemorrhage, aggressive tumor growth, and resistance to therapy. Therefore, the potential role of this molecule in the tumor formation and progression of BPDCN warrants additional exploration. PMID- 24225901 TI - Iron regulation in athletes: exploring the menstrual cycle and effects of different exercise modalities on hepcidin production. AB - The trace element iron plays a number of crucial physiological roles within the body. Despite its importance, iron deficiency remains a common problem among athletes. As an individual's iron stores become depleted, it can affect their well-being and athletic capacity. Recently, altered iron metabolism in athletes has been attributed to postexercise increases in the iron regulatory hormone hepcidin, which has been reported to be upregulated by exercise-induced increases in the inflammatory cytokine interleukin-6. As such, when hepcidin levels are elevated, iron absorption and recycling may be compromised. To date, however, most studies have explored the acute postexercise hepcidin response, with limited research seeking to minimize/attenuate these increases. This review summarizes the current knowledge regarding the postexercise hepcidin response under a variety of exercise scenarios and highlights potential areas for future research such as: a) the use of hormones though the female oral contraceptive pill to manipulate the postexercise hepcidin response, b) comparing the use of different exercise modes (e.g., cycling vs. running) on hepcidin regulation. PMID- 24225902 TI - VapC20 of Mycobacterium tuberculosis cleaves the sarcin-ricin loop of 23S rRNA. AB - The highly persistent and often lethal human pathogen, Mycobacterium tuberculosis contains at least 88 toxin-antitoxin genes. More than half of these encode VapC PIN domain endoribonucleases that inhibit cell growth by unknown mechanisms. Here we show that VapC20 of M. tuberculosis inhibits translation by cleavage of the Sarcin-Ricin loop (SRL) of 23S ribosomal RNA at the same position where Sarcin and other eukaryotic ribotoxins cleave. Toxin-inhibited cells can be rescued by the expression of the antitoxin, thereby raising the possibility that vapC20 contributes to the extreme persistence exhibited by M. tuberculosis. VapC20 cleavage is inhibited by mutations in the SRL that flank the cleavage site but not by changes elsewhere in the loop. Disruption of the SRL stem abolishes cleavage; however, further mutations that restore the SRL stem structure restore cleavage, revealing that the structure rather than the exact sequence of the SRL is important for this activity. PMID- 24225903 TI - Novel, electrolyte solutions comprising fully inorganic salts with high anodic stability for rechargeable magnesium batteries. AB - Herein the first inorganic magnesium salt solution capable of highly reversible magnesium electrodeposition is presented. Synthesized by acid-base reaction of MgCl2 and Lewis acidic compounds such as AlCl3, this salt class demonstrates upwards of 99% Coulombic efficiency, deposition overpotential of <200 mV, and anodic stability of 3.1 V. PMID- 24225904 TI - Heterogeneity among studies in rates of decline of antiretroviral therapy adherence over time: results from the multisite adherence collaboration on HIV 14 study. AB - OBJECTIVE: To use electronic drug monitoring to determine if adherence to HIV antiretroviral therapy (ART) changes over time, whether changes are linear, and how the declines vary by study. DESIGN: We conducted a longitudinal study of pooled data from 11 different studies of HIV-infected adults using ART. The main outcome was ART adherence (percent of prescribed doses taken) measured by electronic drug monitoring. We modeled and compared changes in adherence over time using repeated measures linear mixed effects models and generalized additive mixed models (GAMMs). Indicator variables were used to examine the impact of individual studies, and the variation across studies was evaluated using study specific parameter estimates calculated by using interaction terms of study and time. RESULTS: The mean age of the subjects was 41 years, 35% were female, most had high school education or less, and 46% were African American. In GAMMs, adherence declined over time. The GAMMs further suggested that the decline was nonlinear, and in both sets of models, there was considerable study-to-study variability in how adherence changed over time. LIMITATIONS: Findings may not be generalizable to non-US populations or to patients not in clinical studies. CONCLUSIONS: Although overall ART adherence declined with time, not all studies showed declines, and a number of patterns of change were seen. Studies that identify clinical and organizational factors associated with these different patterns are needed. Models of changes in adherence with time should take account of possible nonlinear effects. PMID- 24225905 TI - One-pot phase transfer and surface modification of CdSe-ZnS quantum dots using a synthetic functional copolymer. AB - We present a facile, one-pot procedure for the organic-to-water phase transfer and biofunctionalization of semiconductor nanocrystals (quantum dots, or QDs) which employs a synthetic functional copolymer, namely poly(DMA-NAS-MAPS), consisting of three components: a surface interacting monomer, N,N dimethylacrylamide (DMA), a chemically reactive monomer, N-acryloyloxysuccinimide (NAS), and a silane monomer, [3-(methacryloyloxy)-propyl]-trimethoxysilane (MAPS). The nanocrystals were transferred to water by exploiting the amphiphilic character of the copolymer backbone. Hydrolyzed MAPS units contributed to improve the solubility of QDs in water, whereas NAS exhibited reactivity toward biomolecules. A solution of streptavidin in phosphate buffer exhibited good dispersion ability leading to a clear and transparent colloidal suspension, indicative of good QD dispersion during phase transfer and purification. Unlike most of the published methods, the proposed functionalization approach does not require coupling agents and multistep reactions. PMID- 24225906 TI - Genetically encoded fluorescent redox probes. AB - Redox processes are involved in almost every cell of the body as a consequence of aerobic life. In the past decades, redox biology has been increasingly recognized as one of the key themes in cell signaling. The progress has been accelerated by development of fluorescent probes that can monitor redox conditions and dynamics in cells and cell compartments. This short paper focuses on fluorescent redox probes that are genetically encoded, and discusses their properties, molecular mechanism, advantages and pitfalls. Our recent work on reaction-based encoded probes that are responsive to particular redox signaling molecules is also reviewed. Future challenges and directions are also commented. PMID- 24225907 TI - Process mining for individualized behavior modeling using wireless tracking in nursing homes. AB - The analysis of human behavior patterns is increasingly used for several research fields. The individualized modeling of behavior using classical techniques requires too much time and resources to be effective. A possible solution would be the use of pattern recognition techniques to automatically infer models to allow experts to understand individual behavior. However, traditional pattern recognition algorithms infer models that are not readily understood by human experts. This limits the capacity to benefit from the inferred models. Process mining technologies can infer models as workflows, specifically designed to be understood by experts, enabling them to detect specific behavior patterns in users. In this paper, the eMotiva process mining algorithms are presented. These algorithms filter, infer and visualize workflows. The workflows are inferred from the samples produced by an indoor location system that stores the location of a resident in a nursing home. The visualization tool is able to compare and highlight behavior patterns in order to facilitate expert understanding of human behavior. This tool was tested with nine real users that were monitored for a 25 week period. The results achieved suggest that the behavior of users is continuously evolving and changing and that this change can be measured, allowing for behavioral change detection. PMID- 24225909 TI - Improving oral function and cosmesis in a case of Freeman-Sheldon syndrome. AB - Children born with the rare congenital condition Freeman-Sheldon syndrome (FSS) have a characteristic facial appearance: microstomia, a long philtrum, 'H-shaped' chin abnormality and 'pinched lips' in addition to extra-facial features such as kyphoscoliosis and hand deformities. Such children often have problems with oral continence and difficulties with speech leading to both nutritional and psychosocial concerns. Prompt correction through surgery is therefore important in effectively managing the condition. We report the case of a 7-year-old girl who presented with the appearance of scarred lips with difficulties in closing her mouth, a speech impediment and oral incontinence. Using a muscle-sparing technique to reconstruct the upper and lower lips, better oral continence was achieved alongside markedly improved speech and an aesthetically pleasing result. Taken together, this case aptly illustrates the benefits of lip reconstruction in improving function and cosmesis in patients with FSS. PMID- 24225908 TI - Microfluidic transwell inserts for generation of tissue culture-friendly gradients in well plates. AB - Gradients of biochemical molecules play a key role in many physiological processes such as axon growth, tissue morphogenesis, and trans-epithelium nutrient transport, as well as in pathophysiological phenomena such as wound healing, immune response, bacterial invasion, and cancer metastasis. In this paper, we report a microfluidic transwell insert for generating quantifiable concentration gradients in a user-friendly and modular format that is compatible with conventional cell cultures and with tissue explant cultures. The device is simply inserted into a standard 6-well plate, where it hangs self-supported at a distance of ~250 MUm above the cell culture surface. The gradient is created by small microflows from the device, through an integrated track-etched porous membrane, into the cell culture well. The microfluidic transwell can deliver stable, quantifiable gradients over a large area with extremely low fluid shear stress to dissociated cells or tissue explants cultured independently on the surface of a 6-well plate. We used finite-element modeling to describe the porous membrane flow and molecular transport and to predict gradients generated by the device. Using the device, we applied a gradient of the chemotactic peptide N formyl-met-leu-phe (fMLP) to a large population of HL-60 cells (a neutrophil cell line) and directly observed the migration with time-lapse microscopy. On quantification of the chemotactic response with an automated tracking algorithm, we found 74% of the cells moving towards the gradient. Additionally, the modular design and low fluid shear stress made it possible to apply gradients of growth factors and second messengers to mouse retinal explant cultures. With a simplified interface and well-defined gradients, the microfluidic transwell device has potential for broad applications to gradient-sensing biology. PMID- 24225910 TI - Durable recovery of the macular architecture and functionality of a diagnosed age related macular degeneration 1 year after a single intravitreal injection of dobesilate. AB - Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID- 24225911 TI - Lipoma of the sinus tarsi. AB - Lipoma is rarely found in the foot. It is usually asymptomatic although sometimes can present with pain. We report a case of lipoma of the sinus tarsi presenting with functional instability. PMID- 24225912 TI - Giant leiomyoma of the oesophagus with eosinophilic infiltration. AB - The most common benign tumour of the oesophagus is leiomyoma. Haemopoietic elements rarely infiltrate oesophageal leiomyoma. We report the case of a 24-year old man with a long history of intermittent dysphagia. Endoscopy revealed external compression with normal oesophageal mucosa. A barium swallow study showed a defect in the oesophageal wall and a narrow oesophageal lumen. A CT scan of the chest confirmed a mass in the mid-oesophagus. A tumour was excised and the histology report revealed leiomyoma infiltrated with eosinophils, which is a rare variant. PMID- 24225913 TI - Immunoassay and ultrastructural localization of isopentenyladenine and related cytokinins using monoclonal antibodies. AB - Two hybridoma cell lines, J40-IV-A1 and J40-IV-C4 were obtained from a fusion of spleen cells of Balb/c mice immunized against an isopentenyladenosine-bovine serum albumin conjugate with X63. Ag 8.653 myeloma cells. These hybrids secrete monoclonal antibodies of the immunoglobulin G (IgG) class and share high affinities and specificities to isopentenyladenine and isopentenyladenosine suitable for the detection of femtomole amounts of these cytokinins in plant extracts by enzyme-linked immunosorbent assay (ELISA). One of the monoclonal antibodies (J40-IV-C4) has been employed to localize isopentenyladenine immunoreactivity in a cytokinin-over-producing mutant of the moss, Physcomitrella patens. After fixation and embedding at low temperature, immunoreactivity was visualized in protonemal filaments of the moss mutant by the use of indirect immunogold labelling. In the mutant, the labelling was predominantly in the wall of the protonemal cells. Neither the wild-type nor control treatments showed any labelling. The signficance of these observations is discussed with respect to the applicability of immunocytochemical techniques for the localization of low molecular-weight compounds in plant tissue. PMID- 24225914 TI - The effects of immobilization on the biochemical, physiological and morphological features of Anabaena azollae. AB - Anabaena azollae, a presumptive isolate from Azolla filiculoides, was immobilized in polyurethane foam, hydrophilic polyvinyl foam and alginate. When viewed by low temperature scanning electron microscopy a thick mucilage layer covered the surface of both cells and matrix; this closely resembles the mode of attachment of the symbiont Anabaena in the Azolla leaf cavity. The heterocyst frequency of the immobilized A. azollae doubled relative to free-living cells and reached a level of 14-17%. Immobilization induced increases in both hydrogen production via nitrogenase or hydrogenase and in the rates and stabilization of acetylene reduction (N2-fixation). Ammonia production by immobilized cells with L methionine-D,L-sulfoximine (MSX) is greater than that of freeliving cells. Immobilized cells without MSX were, however, able to excrete ammonium at lower rates thus emulating the characteristic of the symbiotic cyanobacteria (A. azollae) in the leaf cavity of Azolla. PMID- 24225915 TI - Observations on dividing plastids in the protonema of the moss Funaria hygrometrica Sibth. : Arrangement of microtubules and filaments. AB - The process of division was investigated in the different types of plastids found in the tip cell of the protonema of Funaria hygrometrica Sibth. There were no structural changes in the envelope membranes of any of the plastid types during the initial stage of division. As the process of constriction advanced, thylakoids were locally disintegrated and sometimes starch grains in the isthmus were locally dissolved. In the isthmus, tightly constricted plastids were characterized by an undulating envelope and an increasing number of vesicles. After three-dimensional reconstruction of electronmicrographs a distinct filamentous structure was observed in the plane of division outside the plastid but close to the envelope. At different stages of division the constricted regions were partly surrounded by one or a few filaments. The roundish plastids in the apical zone were accompanied by single microtubule bundles, and the spindle-shaped plastids in the cell base were surrounded by single microtubules and microtubule bundles. A model of co-operation between microtubules and the filamentous structure in the division process is discussed. PMID- 24225916 TI - Do some plant responses to cytokinins involve the cyanide-resistant respiratory pathway? AB - A disengagement of the cyanide-resistant, alternative respiratory pathway in soybean (Glycine max (L.) Merr.) callus tissue was observed prior to the start of deoxyisoflavone production stimulated by addition of the cytokinin benzyladenine. To test whether this loss of alternativepathway activity was part of the response to cytokinin, inhibitors of the alternative pathway were assayed for their ability to elicit cytokinin-like responses. Salicylhydroxamic acid (SHAM) was found to produce a deoxyisoflavone difference spectrum similar to that observed following treatment of the callus tissue with benzyladenine, while propyl gallate (PG) was without effect. Both SHAM and PG were further tested for cytokinin-like activity in other bioassays. In two anti-senescence bioassays using leaf tissue (of Avena sativa L. and Xanthium pensylvanicum Wallr.) and in the Cucumis sativus L. bioassay which measures stimulation of weight gain by excised cotyledons, both SHAM and PG were effective "cytokinins" at 1 mM and 0.1 mM, respectively. In two other bioassays (betacyanin formation in Amaranthus caudatus L. seedlings and the soybean-callus celldivision assay), SHAM appeared to be toxic. These results substantiate the suggestion that effects on the alternative pathway may play a role in some cytokinin responses and further raise the question of what should be considered a true cytokinin response. PMID- 24225917 TI - Immunogold-localization and synthesis of an oil-body membrane protein in developing soybean seeds. AB - The synthesis of a major oil-body membrane brotein was studied in maturing soybean (Glycine max (L.) Merr.) cotyledons. The membrane contained four abundant proteins with apparent molecular mass (Mr) of 34000, 24000, 18000 and 17000. The Mr=24000 protein (mP 24) was selected for more detailed analysis. The protein was purified to apparent homogeneity by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and isolated from the gel by electroelution or chemical hydrolysis of gel crosslinks. It was then used to elicit rabbit antibodies which were judged to be specific when assayed by SDS PAGE-immunoblot procedures. The mP 24 was localized in immature soybean cotyledon cells by indirect immunogold procedures on thin sections of Lowicryl- and LR White-embedded tissue. Indirect labeling with the primary antiserum followed by colloidal gold-protein A showed specific labeling of the oil-body membrane and an absence of label on the other subcellular organelles including the endoplasmic reticulum (ER). Parallel tissue samples were studied by conventional transmission electron microscopy. Although segments of the ER were observed to be closely juxtaposed to the oil bodies, continuity between the two organelles was not observed. The synthesis of mP 24 was studied by in-vitro translation and in-vivo labeling with [(3)H]leucine followed by indirect immunoaffinity isolation of the labeled products. The SDS-PAGE fluorography results indicated that the primary translation product and the in-vivo synthesized protein have the same Mr, and this is also the same Mr as the protein in the mature membrane. PMID- 24225918 TI - The permeability of electroporated cells and protoplasts of sugar beet. AB - A simple method has been developed to determine the changes in permeability of protoplasts and intact cells when electroporated. Cells and protoplasts of sugar beet, Beta vulgaris L., were subjected to electric pulse treatments of different field strengths, pulse number and pulse duration, and the ability to accumulate and retain the hydrophilic dye phenosafranine was determined spectrophotometrically. Results of timecourse studies of phenosafranine accumulation and retention indicated that pores are formed or enlarged rapidly in the plasmamembrane and remain permeable to phenosafranine for relatively long periods; the half-life of the 'pores" was temperaturedependent. Both cells and protoplasts retained the highest levels of phenosafranine when supplied with a series of five rectangular pulses of 50 MUs duration and of field strength 2500 V.cm(-1). If these parameters were exceeded, The phenosafranine content was reduced, concomitant with a decline in viability as indicated by fluorescein diacetate staining, indicating the loss of the integrity of the plasmamembrane. The pattern of accumulation and retention by protoplasts of radioactivity from [(3)H]pABD1, a modified bacterial plasmid, was similar to that of phenosafranine, but uptake of the plasmid by cells was not demonstrated. The mothod can be used to determine conditions for the optimum permeabilization of protoplasts for direct gene transfer. PMID- 24225919 TI - Isolation and characterization of a genomic clone encoding the beta-subunit of beta-conglycinin. AB - beta-Conglycinin, and abundant storage protein in soybean (Glycine max (L.) Merr.) seeds, is a trimeric protein consisting of various isomers containing the three subunits, alpha', alpha and beta. Accumulation of the beta-subunit is unique because it appears to be regulated by a variety of developmental and environmental signals. In this paper we describe the isolation and characterization of a genomic clone encoding the beta-subunit of beta conglycinin. The genomic clone was characterized by restriction-enzyme mapping and partial DNA sequence analysis, by immunoprecipitation of a hybrid-selected invitro translation product, and by RNA blot hybridization reactions. An mRNA of approx. 1700 nucleotides hybridized to an internal 2-kilobase (kb) region of this 4.4-kb cloned DNA restriction fragment and was translated to yield a polypeptide with an approximate molecular weight of 48 kilodalton. This polypeptide is immunoprecipitable by antibody against beta-conglycinin and is of appropriate size to represent the precursor polypeptide of the beta-subunit. When this sequence was used as a probe in RNA blot hybridization experiments, the beta-gene transcript was first detected by stage K and accumulated through stage O during soybean seed development, coincident with appearance of the beta-subunit. Partial DNA sequence analysis of the 5' end of the gene confirmed that the isolated gene encoded a beta-subunit, based upon the previously reported amino terminal sequence for this protein. Genomic DNA blot hybridization analyses indicate that multiple DNA restriction fragments are highly homologous to this cloned beta-gene sequence. PMID- 24225920 TI - Expression of the beta-subunit of beta-conglycinin in seeds of transgenic plants. AB - Soybean (Glycine max (L.) Merr.) seeds contain the storage protein beta conglycinin, encoded by a multigene family. beta-Conglycinin consists of three subunits; alpha', alpha, and beta. A genomic clone for a beta-subunit of beta conglycinin has been characterized by restriction-enzyme mapping and hybrid selected in-vitro translation followed by immunoprecipitation. In order to determine the developmental regulation of this beta-subunit gene, its expression was studied in seeds of transgenic petunia (Petunia hybrida) and tobacco (Nicotiana tabacum L.) plants. The beta-subunit expressed in seeds of petunia and tobacco was recognized by anti-beta-conglycinin serum at a relative molecular mass of 53 000, equivalent to that of the native protein. Separation of the petunia-seed proteins by isoelectric focusing followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblot analysis showed that multiple isoelectric forms of the beta-subunit were produced. There was approximately a twofold variation in the accumulation of the beta-subunit protein in the mature seeds of transgenic petunia plants, each containing a single beta-subunit gene. However, the level of protein accumulation in mature seeds and the amount of beta subunit mRNA in developing seeds was not correlated. Accumulation of the beta subunit protein in transgenic seeds was less than the alpha'-subunit protein that accumulated in transgenic petunia seeds containing a single alpha'-subunit gene and less than the amount of the beta-subunit in mature soybean seeds which contain 8-13 beta-subunit genes. In transgenic tobacco plants, the accumulation of the beta-subunit protein in seeds was generally well correlated with the number of genes that were incorporated in the different transformants. PMID- 24225921 TI - The levels of two distinct species of phytochrome are regulated differently during germination in Avena sativa L. AB - The abundance and molecular mass of phytochrome in germinating embryos of A. sativa (oat) grown in light or darkness have been monitored using immunoblot and spectrophotometric assays. Immunoblot analysis shows that imbibed but quiescent embryos have two immunochemically distinct species of phytochrome with monomeric molecular masses of 124 and 118 kDa (kdalton). The 118-kDa species has the properties of the 118-kDa phytochrome extracted from fully green oat tissue (J.G. Tokuhisa, S.M. Daniels, P.H. Quail, 1985, Planta 164, 321-332), whereas the 124 kDa polypeptide appears similar to the well-characterized photoreceptor of etiolated tissue. The capacity of antibodies directed against etiolated-oat phytochrome to immunoprecipitate the 124-kDa species but not the 118-kDa species has been exploited to quantitate the levels of each separately over a 72-h time course of germination and seedling development. The abundance of the 124-kDa molecule increases at least 200-fold in etiolated seedlings over 72 h whereas in light-grown seedlings the level of this molecule is relatively constant. In contrast, the amount of the 118-kDa species increases only twofold in both dark- and light-grown seedlings over the same period of time. These data indicate that whereas the abundance of 124-kDa phytochrome is regulated at the protein level by the well-documented, differential stability of the red- and far-red-absorbing forms in vivo, the 118-kDa molecule is present at a low constitutive level, presumably reflecting no such difference in the stability of the two spectral forms. PMID- 24225922 TI - Photoinhibition, 77K chlorophyll fluorescence quenching and phosphorylation of the light-harvesting chlorophyll-protein complex of photosystem II in soybean leaves. AB - When the capacity of leaves for orderly dissipation of excitation energy in photosynthesis is exceeded, one mechanism by which the excess energy appears to be dissipated is through a nonradiative decay process. This process is observed as a reversible quenching of chlorophyll fluorescence emission (77K) from both photosystem II and photosystem I which persists in darkness (Demmig and Bjorkman 1987, Planta 171, 171-184). Fluorescence quenching was induced in soybean (Glycine max (L.) Merr.) leaves by two methods: 1) changing the composition of the gas surrounding the leaf from normal air to 2% O2, 0% CO2 at a low, constant photon flux density (PFD=photon fluence rate), and 2) increasing the PFD in the presence of normal air. In either case the quenching was fully reversible after return to the original condition (low PFD, normal air). The half-time of the relaxation of the quenching was in the order of 30 min. Both treatments resulted in reversible dephosphorylation of the light-harvesting chlorophyll-protein complex of photosystem II (LHC-II). Treatment under photoinhibitory conditions (high PFD plus chloramphenicol) also caused dephosphorylation of LHC-II. Therefore, phosphorylation of LHC-II cannot account for the observed fluorescence quenching. In addition, our results indicate that in vivo a factor other than the redox state of the plastoquinone pool controls LHC-II phosphorylation. This factor may be DeltapH, the pH gradient across the thylakoid membranes. PMID- 24225923 TI - Ethylene regulation of beta-1,3-glucanase in tobacco. AB - Ethylene treatment (approx. 20 MUl .1(-1) in air for 2 d) of tobacco (Nicotiana tabacum L. cv. Havana 425) plants markedly increases the endo-beta-1,3-glucanase (EC 3.2.1.39) content of leaves. The antigenic form of the enzyme induced is the same one whose production is blocked by treating cultured cells with combinations of auxin (1.1 . 10(-5) M alpha-naphthaleneacetic acid) and cytokinin (1.4 . 10( 6) M kinetin). Evidence is presented that cultured tobacco cells require ethylene for beta-1,3-glucanase accumulation: i) ethylene treatment increased the accumulation of ?-1,3-glucanase in callus tissues >10 d after subculturing and in cell-suspension cultures; ii) callus tissues can produce ethylene; iii) conditions known to inhibit ethylene production (1 mM CoCl2; 33 degrees C treatment) or ethylene action (approx. 1.6 mmol . 1(-1) norbornadiene in air) inhibited beta-1,3-glucanase accumulation by callus tissues treated for 4 d following subculturing; and, these inhibitory effects were prevented by exogenous ethylene. Combinations of auxin and cytokinin blocked ethylene-induced accumulation of beta-1,3-glucanase by cell-suspension cultures. The results favor a model in which ethylene induces results favor a model in which ethylene induces beta 1,3-glucanase accumulation, and auxin and cytokinin inhibit this induction process. PMID- 24225924 TI - Temporal and light control of plastid transcript levels for proteins involved in photosynthesis during mustard (Sinapis alba L.) seedling development. AB - Transcript levels of four plastid genes encoding constituents of the photosynthetic apparatus were assessed in cotyledons of developing mustard (Sinapis alba L.) seedlings. These genes, encoding the P700 apoproteins of photosystem I, the alpha subunit of the extrinsic CF1 moiety of the plastid ATP synthase complex, and the cytochromes f and b 6, have been localized and mapped previously on mustard chloroplast DNA (G. Dietrich and G. Link, 1985 Curr. Genet. 9, 683-692). Dot blot and Northern hybridization analysis provides evidence that in dark-grown seedlings transcript levels of all four genes rise between 30 h and 72 h after sowing and thereafter fall again, pointing to the existence of an endogenous, light-independent, developmental program. In light-grown seedlings, an additional enhancement of transcript levels beyond, the dark values becomes noticeable at approx. 30-36 h and then continues throughout the subsequent "light responsive" phase until 96 h after sowing. This is consistent with a photoregulated modulation mechanism operating once "competence" has been reached. Enhanced transcript accumulation occurs following continuous illumination by either white light or (photosynthetically inefficient) far-red light thought to operate mainly through phytochrome. However, the degree of light enhancement for the transcript specifying the P700 apoprotiens is higher with white light than with far-red light, implying involvement of additional photoreceptor(s) mediating this response. In addition to the endogenous gross regulation and light enhancement, a fine regulation of transcript levels seems to operate, as indicated by temporal variations of two related transcripts originating from the cytochrome-f gene region. The observed developmental and photocontrolled changes in specific transcript levels for photosynthesis proteins are only reflected in part by changes in total RNA content and do not appear due to light-dark differences in plastid-DNA copy number during mustard seedling development. PMID- 24225925 TI - Regulation of auxin transport in pea (Pisum sativum L.) by phenylacetic acid: effects on the components of transmembrane transport of indol-3yl-acetic acid. AB - Phenylacetic acid (PAA), a naturally-occurring acidic plant growth substance, was readily taken up by pea (Pisum sativum L. cv. Alderman) stem segments from buffered external solutions by a pH-dependent, non-mediated diffusion. Net uptake from a 0.2 MUM solution at pH 4.5 proceeded at a constant rate for at least 60 min and, up to approx. 100 MUM, the rate of uptake was directly proportional to the external concentration of the compound. The net rate of uptake of PAA was not affected by the inclusion of indol-3yl-acetic acid (IAA) in the uptake medium (up to approx. 30 MUM) and, unlike the net uptake of IAA, was not stimulated by N-1 naphthylphthalamic acid (NPA) or 2,3,5-triiodobenzoic acid. At an external concentration of 0.2 MUM and pH 4.5, the net rate of uptake of PAA was about twice that of IAA. It was concluded that the uptake of PAA did not involve the participation of carriers and that PAA was not a transported substrate for the carriers involved in the uptake and polar transport of IAA. Nevertheless, the inclusion of 3-100 MUM unlabelled PAA in the external medium greatly stimulated the uptake by pea stem segments of [1-(14)C]IAA (external concentration 0.2 MUM). It was concluded that whilst PAA was not a transported substrate for the NPA sensitive IAA efflux carrier, it interacted with this carrier to inhibit IAA efflux from cells. Over the concentration range 3-100 MUM, PAA progressively reduced the stimulatory effect of NPA on IAA uptake, indicating that PAA also inhibited carrier-mediated uptake of IAA. The consequences of these observations for the regulation of polar auxin transport are discussed. PMID- 24225926 TI - Regulation of auxin transport in pea (Pisum sativum L.) by phenylacetic acid: inhibition of polar auxin transport in intact plants and stem segments. AB - The transport of [(14)C]phenylacetic acid (PAA) in intact plants and stem segments of light-grown pea (Pisum sativum L. cv. Alderman) plants was investigated and compared with the transport of [(14)C]indiol-3yl-acetic acid (IAA). Although PAA was readily taken up by apical tissues, unlike IAA it did not undergo long-distance transport in the stem. The absence of PAA export from the apex was shown not to be the consequence of its failure to be taken up or of its metabolism. Only a weak diffusive movement of PAA was observed in isolated stem segments which readily transported IAA. When [1-(14)C]PAA was applied to a mature foliage leaf in light, only 5.4% of the (14)C recovered in ethanol extracts (89.6% of applied (14)C) had been exported from the leaf after 6.0 h. When applied to the corresponding leaf, [(14)C]sucrose was readily exported (46.4% of the total recovered ethanol-soluble (14)C after 6.0 h). [1-(14)C]phenylacetic acid applied to the root system was readily taken up but, after 5.0 h, 99.3% of the recovered (14)C was still in the root system.When applied to the stem of intact plants (either in lanolin at 10 mg.g(-1), or as a 10(-4) M solution), unlabelled PAA blocked the transport through the stem of [1-(14)C]IAA applied to the apical bud, and caused IAA to accumulate in the PAA-treated region of the stem. Applications of PAA to the stem also inhibited the basipetal polar transport of [1-(14)C]IAA in isolated stem segments. These results are consistent with recent observations (C.F. Johnson and D.A. Morris, 1987, Planta 172, 400 407) that no carriers for PAA occur in the plasma membrane of the light-grown pea stem, but that PAA can inhibit the carrier-mediated efflux of IAA from cells. The possible functions of endogenous PAA are discussed and its is suggested that an important role of the compound may be to modulate the polar transport and-or accumulation by cells of IAA. PMID- 24225927 TI - A selective assay for prephenate aminotransferase activity in suspension-cultured cells of Nicotiana silvestris. AB - Prephenate aminotransferase in Nicotiana silvestris Speg. et Comes is highly stable to thermal treatment. This property was exploited to obtain, by treatment at 70 degrees C for 10 min, a residual level (1-4%) of aspartate aminotransferase activity that proved to be catalyzed exclusively by prephenate aminotransferase. The latter enzyme was the most mobile of all aspartate aminotransferase bands during polyacrylamide-gel electrophoresis conducted under non-denaturing conditions. This methodology for convenient assay of prephenate aminotransferase in crude extracts, as demonstrated for N. silvestris, may generally apply to higher plants since prephenate aminotransferase from a variety of plant sources has been found to exhibit high thermal stability. PMID- 24225928 TI - Effects of R-(1-amino-2-phenylethyl)phosphonic acid on glyceollin accumulation and expression of resistance to Phytophthora megasperma f.sp. glycinea in soybean. AB - (R)-(1-Amino-2-phenylethyl)phosphonic acid (R-APEP), an inhibitor of phenylalanine ammonia-lyase (PAL), was applied to the tap root of 42-h-old soybean (Glycine max. (L.) Merrill cv. Harosoy 63) seedlings during inoculation with zoospores of the incompatible race 1 of Phytophthora megasperma f.sp. glycinea (Pmg1) for 2 h and during a subsequent incubation period. In contrast to L-2-aminooxy-3-phenylpropionic acid, R-APEP was not toxic to the zoospores which remained virulent in presence of the inhibitor. A 50% inhibition of PAL activity in vitro was observed with 4.2 MUM R-APEP and with 36 MUM of the S-enantiomer. When R-APEP at 330 MUM was applied for a total of 36 h to the seedlings, resistance against Pmg 1 was abolished. Such seedlings were indistinguishable in appearance from those seedlings which had been inoculated with the compatible race 3 of Pmg. Roots treated with R-APEP at 330 MUM showed a reduction of about 47% in glyceollin content when measured 12 h after inoculation, and with 1 mM a 67% reduction. In contrast, treatment with S-APEP (1 mM) caused only a 20% reduction in glyceollin content. As determined by indirect immunofluorescence of fungal hyphae in cryotome cross-sections of roots, the growth pattern of the incompatible race 1 of Pmg changed to that of the compatible race 3 under conditions where R-APEP caused loss of resistance against Pmg 1. The results support the concept of an important role of glyceollin in resistance of soybean against incompatible races of the fungus. PMID- 24225929 TI - Phoretic egg parasitoid,Telenomus euproctidis (Hymenoptera: Scelionidae), uses sex pheromone of tussock mothEuproctis taiwana (Lepidoptera: Lymantriidae) as a kairomone. AB - The phoretic egg parasitoid,Telenomus euproctidis Wilcox (Hymenoptera: Scelionidae) was found more frequently on virgin than on mated female moths ofEuproctis taiwana (Shiraki) (Lepidoptera: Lymantriidae), when virgin and mated moths were exposed concurrently in the field for 24 hr. A synthetic component of the moth's sex pheromone. (Z)-16-methyl-9-heptadecenyl isobutyrate, attracted both the wasp,T. euproctidis, and maleE. taiwana. These findings suggest thatT. euproctidis uses the sex pheromone of the female moth,E. taiwana, as a kairomone to locate a host female moth and through her the host eggs. PMID- 24225930 TI - Behavioral responses ofSpodoptera littoralis males to sex pheromone components and virgin females in wind tunnel. AB - The major component of the sex pheromone of femaleSpodoptera littoralis, (Z,E) 9,11-tetradecadienyl acetate (1), elicited all steps of the male behavioral sequence, i.e., wing fanning and taking flight, oriented upwind flight and arrival to the middle of the tunnel, close approach and contact with the source. The activity was equivalent to that elicited by virgin females. In the range of doses tested, the dosage of1 had no significant effect on the number of source contacts. Male response was significantly affected by light intensity, being optimum at 3 lux. Activity of the minor components (Z)-9-tetradecenyl acetate (2), (E)-11-tetradecenyl acetate (3), tetradecyl acetate (4), (Z)-11-tetradecenyl acetate (5), and (Z,E)-9,12-tetradecadienyl acetate (6) was significantly lower than that of the major component when assayed individually. In multicomponent blends compound4 appeared to strongly decrease the number of males arrested at the source, the effect being particularly important when compound5 was present in the blend. Results of single sensillum experiments confirmed the existence of two main physiologically distinct sensillar types. The most common type of sensilla contained a neuron that responded specifically to compound1. A second type of sensilla, located laterally on the ventral sensory surface, contained two receptor neurons responding to compound6 and to (Z)-9-tetradecenol. Among short sensilla, one hair responded to compound4 and could represent a minor sensillar type. No sensory neuron was found to detect the other minor pheromone compounds2, 3, and5. PMID- 24225931 TI - Sex pheromone ofStenoma cecropia Meyrick (Lepidoptera: Elachistidae). AB - (Z,E)-9,11-tetradecadienal (Z9,E11-14: Ald; 11%), (Z,E)-9,11,13-tetradecatrienal (Z9,E11, 13-14: Ald; 67%), (Z,E)-9,11-tetradecadienyl acetate (Z9,E11-14: Ac, 5.5%), and (Z,E)-9,11,13-tetradecatrienyl acetate (Z9,E11,13-14: Ac; 16.5%) were identified in the extracts of female pheromone glands ofStenoma cecropia (Lepidoptera: Elachistidae). From electroantennograms and single sensillum recordings, receptors toZ9,E11,13-14:Ald andZ9,E11-14: Ald were found on male antenna. Behavioral data were obtained from olfactometric tests in the laboratory and field trapping experiments in Colombia. It appeared that a blend ofZ9,E11,13 14:Ald (83%) andZ9,E11-14:Ald (17%) was attractive to males. These aldehydes are assumed to be components of the sex pheromone ofS. cecropia, whereas the acetates found in gland extracts might be precursors of the pheromone. PMID- 24225932 TI - Allelopathic potential of well water fromPluchea lanceolata-infested cultivated fields. AB - Pluchea lanceolata, an allelopathic perennial weed, has an extensive deep root and rhizome system. The objective of the present study was to determine the allelopathic potential of well water collected from weed-infested cultivated fields. Results indicate that well water recovered fromP. lanceolata-infested cultivated fields inhibited the shoot growth of pea, chick pea, mustard, and wheat under greenhouse conditions. Two phenolic compounds, phenol and phloroglucinol, were isolated and identified from collected well water using UV spectroscopy. The allelopathic potential of the aqueous extract of the two compounds was determined by growth experiments with 10(4) M solutions of the compounds. As a consequence of repeated irrigation with well water fromP. lanceolata-infested fields, higher levels of phenolics can accumulate in the soil, which may contribue to increased interference to crop plants. The present study is of significance since it cautions on the use of well water for irrigating cultivated fields infested with the perennial allelopathic weed (P. lanceolata) with dense subterranean systems and emphasizes the importance of controlling such weeds in cultivated fields. PMID- 24225933 TI - Within-plant variation in concentrations of amino acids, sugar, and sinigrin in phloem sap of black mustard,Brassica nigra (L.) Koch (Cruciferae). AB - Although within-plant variation in the nutrient and allelochemical composition of phloem sap has been invoked to explain patterns of host use by phloem-feeding insects, little is known about within-plant variation in phloem chemistry. Here I describe a new technique in which I use the green peach aphid,Myzus persicae Sulz., to investigate within-plant variation in the concentrations of chemicals in the phloem sap of black mustard,Brassica nigra (L.) Koch (Cruciferae). Relationships between the concentrations of chemicals in aphid diets and honeydew were established using honeydew from aphids fed on artificial diets with known concentrations of amino acids, sucrose, and sinigrin. These relationships were applied to honeydew from aphids fed on different aged leaves of black mustard to estimate the concentrations of the chemicals in phloem sap. Sinigrin concentration was estimated to be high (>10 mM) in phloem sap in young leaves, calling into question the prevailing opinion that phloem sap contains only low concentrations of allelochemicals. High concentrations may function as defenses against sap-feeding herbivores. Within-plant variation in phloem sap composition was high: (1) young leaves had high concentrations of nutrients (216 mM amino acids, 26% sugar) and sinigrin (>10 mM); (2) mature and presenescent leaves had lower concentrations of nutrients (77-83 mM amino acids, 19-20% sugar) and low concentrations of sinigrin (1-2 mM); and (3) senescing leaves had high concentrations of nutrients (199 mM amino acids, 25% sugar) and low concentrations of sinigrin (3 mM). PMID- 24225934 TI - Influence of alkaloid concentration on acceptability of tall larkspur (Delphinium spp.) to cattle and sheep. AB - Tall larkspur (Delphinium spp.) is a serious toxic plant problem on western U.S. ranges. The major toxins in tall larkspur are methyllycaconitine (MLA) and 14 deacetylnudicauline (14-DAN); the sum of both is termed the toxic alkaloid concentration. Toxic alkaloids comprise about 20-50% of the total alkaloid concentration in tall larkspur. Toxic and total alkaloid concentration generally declines with maturity, whereas cattle and sheep consumption of larkspur typically increases with plant maturity. We hypothesized that cattle and sheep consumption of tall larkspur was negatively related to higher concentrations of total or toxic alkaloid. We compared consumption of several collections of dried, ground larkspur and fresh larkspur in a series of trials. In another trial, a crude alkaloid fraction was extracted with ethanol, added to alfalfa hay, and consumption compared to untreated alfalfa hay, alcohol-treated hay, and the essentially alkaloid-free plant residue. In all cases we correlated amounts eaten with total and toxic alkaloid concentration. A grazing trial was also conducted to relate larkspur consumption over time to alkaloid concentrations. Total alkaloid concentrations in dried, whole-plant collections ranged from 9.3 to 38.8 mg/g of dry weight, whereas toxic alkaloid concentrations varied from 0.0 to 7.1 mg/g. In one pen trial, cattle preferred a larkspur collection (P<0.01) that contained no toxic alkaloids but had a high total alkaloid concentration (39 mg/g). There was no correlation (P>0.05), however, between concentrations of total or toxic alkaloids and amount of dry plant consumed in this or any other trial. Conversely, sheep consumption tended to be negatively influenced by total and toxic alkaloid concentration (P<=0.08). In the trials with extract, cattle preferred the alcohol-treated hay and rejected the alkaloid-free residue (P<0.01), whereas the alkaloid-treated hay was of intermediate acceptability. Cattle preferred the alkaloid-treated hay over the alkaloid-free residue, indicating that alkaloids did not deter consumption. Conversely, the alkaloid treated hay was less preferred than either untreated or alcohol-treated hay, suggesting a negative effect on acceptability. There was no correlation between alkaloid concentration and amount of treated feed eaten. In field trials, the amount of composited, fresh leaves or flowers eaten by cattle was influenced by plant part (P=0.04), but was not related (P>0.05) to alkaloid concentration. Cattle preferred leaves over flowers when offered individual plants differing in phenological stage and/or amount of shade, but alkaloid concentration was not related to consumption. We conclude that knowledge of the concentration of total or toxic alkaloid in tall larkspur will give little or no indication of plant acceptability to cattle. Even though accurate predictions can be made about the potential toxicity of larkspur based on the concentration of toxic alkaloids, predictions about consumption must be based primarily on plant phenology. PMID- 24225935 TI - Sex pheromone of aphid parasitoidPraon volucre (Hymenoptera, Braconidae). AB - Mating in the aphid parasitoidPraon volucre is mediated by a female-produced sex pheromone, which laboratory behavioral studies suggest is released from the abdomen. Gas chromatography coupled with electrophysiological and behavioral assays on males showed one area of activity in an air entrainment sample of virgin females. However, levels of pheromone production are very low and this has so far precluded its identification. PMID- 24225936 TI - Sensitivity ofLemna bioassay interacts with stock-culture period. AB - The effect of stock-culture period on the sensitivity of theLemna bioassay to four different phenolic substances was evaluated in this study. The sensitivity of the bioassay interacted with the stock-culture period of either 11, 14, or 18 days. After a seven-day testp-hydroxybenzoic acid (HBA), vanillic acid (VA),trans cinnamic acid (CA), and ferulic acid (FA) with a concentration of 0.05 mM significantly reduced the number of fronds and the dry weight compared with the untreated control when the stock-culture period had been exactly 14 days. The sensitivity after the shorter (11 days) or longer (18 days) stock-culture period was reduced, and the differences in the dry weight to the untreated control were not significant after a stock culture period of 18 days. The two higher concentrations (0.1 and 0.25 mM) showed stronger inhibition. A comparison of the inhibition at 0.05 mM revealed that the stock-culture period affected the relative toxicity of the four phenolic substances. Since the pH increased in the stock-culture flasks during the 18-day period from 6.25 to 7.9, we hypothesize that differences in theLemna assay can be at least partly attributed to a pH effect, possibly in combination with a relative nutrient deficiency. We recommend a standardization of the stock-culture period to 14 days to improve the sensitivity of theLemna bioassay. PMID- 24225937 TI - Chemoecological role of mammalian urine in host location by tsetse,Glossina spp. (Diptera: Glossinidae). AB - Trap catch size was used to investigate whetherGlossina pallidipes andG. longipennis could distinguish between the urine of the African buffalo, cattle, and waterbuck at Nguruman in southwest Kenya. NG2G traps baited with aged urine of these bovids caught significantly more of each tsetse than did the controls. The mean catch of either tsetse species in traps baited with aged urine of buffalo and cattle (tsetse hosts) and waterbuck (a nonhost) did not differ significantly. Aged urine from both tsetse hosts (buffalo and cattle) and the nonhost (waterbuck) was found to contain 4-cresol and 3-n-propylphenol in about the same ratio. However, the aged urine from other tsetse hosts (bushpig and warthog) lacked 3-n-propylphenol. Cattle urine had to be aged outside the soil to produce statistically significant increases in the trap catch ofG. pallidipes. Furthermore, patches of soil on which fresh urine of cattle was deposited, and in which it was aged, failed to effect a significant increase in the trap catch of eitherG. austeni, G. brevipalpis, orG. pallidipes as Gazi, southeast Kenya. The likelihood of tsetse either differentiating its hosts from nonhosts or locating favored hosts by the urine scent appears remote under natural conditions. It is more likely that the chemical signals critical for host location by the tsetse emanate from skin glands rather than volatilize from the urine of mammals. PMID- 24225938 TI - Intrapopulational changes in sex pheromone composition during scotophase in oriental tobacco budworm,Helicoverpa assulta (Guenee) (Lepidoptera: Noctuidae). AB - Solvent extracts of individual pheromone glands were prepared from femaleHelicoverpa assulta (Guenee) at 2-hr intervals throughout the scotophase. The amounts of female sex pheromone components, (Z)-9-hexadecenal, (Z)-11 hexadecenal, (Z)-9-hexadecenyl acetate, and (Z)-11-hexadecenyl acetate, in the extracts were determined by gas chromatographic analysis. Although females called from early scotophase (2 hr) until late scotophase (6 hr) the quantity of extracted pheromone remained high at 8 hr, the end of the scotophase. More than 70% of the pheromone gland extracts contained sex pheromone components regardless of whether the donor females had been called or resting. Pheromone components were absent from gland extracts prepared at the onset of the scotophase. The quantity of (Z)-9-hexadecenal and (Z)-11-hexadecenal increased rapidly to reach a maximum of approximately 260 and 30 ng/female, respectively, that was maintained for up to 8 hr, the duration of the scotophase. The quantity of (Z)-9-hexadecenyl acetate and (Z)-11-hexadecenyl acetate increased continuously during the scotophase to peak at 600 and 30 ng/female, respectively, 8 hr into the scotophase. At the end of scotophase the quantity of all pheromone components decreased significantly. PMID- 24225939 TI - Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma. AB - BACKGROUND AND AIMS: The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk. METHODS: This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers. RESULTS: The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean+/-SD, 4.35+/-1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75 years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither. CONCLUSIONS: Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk. PMID- 24225940 TI - Prevalence and characteristics in coding, classification and diagnosis of diabetes in primary care. AB - INTRODUCTION: Approximately 366 million people worldwide live with diabetes and this figure is expected to rise. Among the correct diagnosis, there will be errors in the diagnosis, classification and coding, resulting in adverse health and financial implications. AIM: To determine the prevalence and characteristics of diagnostic errors in people with diabetes managed in primary care settings. METHODS: We conducted a cross-sectional study in nine general practices in Leicester, UK, from May to August 2011, using a validated electronic toolkit. Searches identified cases with potential errors which were manually checked for accuracy. RESULTS: There were 54 088 patients and 2434 (4.5%) diagnosed with diabetes. Out of 316 people identified with potential errors with the toolkit, 180 (57%) had confirmed errors after manually reviewing the records, resulting in an error prevalence of 7.4%. Correctly coded people on registers had significantly greater glycated haemoglobin (HbA1c) reductions. There were no significant differences between patients with and without errors in their HbA1C, body mass index, age and size of practice. There was also no significant association of the errors with pay-for-performance initiatives; however, those patients not on disease register had worse glycaemic control. CONCLUSIONS: A high prevalence of diabetic diagnostic errors was confirmed using medication, biochemical and demographic data. Larger studies are needed to more accurately assess the scale of this problem. Automation of these processes might be possible, which would allow searches to be even more user friendly. PMID- 24225941 TI - Preserving youth: does rapamycin deliver? AB - Research suggests that the drug rapamycin slows mammalian aging, but a provocative new study has gained attention by claiming to show it does not. PMID- 24225942 TI - Piecing together the puzzle of severe malaria. AB - Severe malaria manifests as several overlapping syndromes with high mortality. Interaction of parasites with endothelial protein C receptors and high parasite biomass have recently been identified as key determinants of severe disease. However, gaps in our understanding of severe malaria might hinder translation of these findings into new therapies. PMID- 24225943 TI - Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. AB - Perturbations in endoplasmic reticulum (ER) homeostasis can evoke stress responses leading to aberrant glucose and lipid metabolism. ER dysfunction is linked to inflammatory disorders, but its role in the pathogenesis of autoimmune type 1 diabetes (T1D) remains unknown. We identified defects in the expression of unfolded protein response (UPR) mediators ATF6 (activating transcription factor 6) and XBP1 (X-box binding protein 1) in beta cells from two different T1D mouse models and then demonstrated similar defects in pancreatic beta cells from T1D patients. Administration of a chemical ER stress mitigator, tauroursodeoxycholic acid (TUDCA), at the prediabetic stage resulted in a marked reduction of diabetes incidence in the T1D mouse models. This reduction was accompanied by (i) a significant decrease in aggressive lymphocytic infiltration in the pancreas, (ii) improved survival and morphology of beta cells, (iii) reduced beta cell apoptosis, (iv) preserved insulin secretion, and (v) restored expression of UPR mediators. TUDCA's actions were dependent on ATF6 and were lost in mice with beta cell-specific deletion of ATF6. These data indicate that proper maintenance of the UPR is essential for the preservation of beta cells and that defects in this process can be chemically restored for preventive or therapeutic interventions in T1D. PMID- 24225944 TI - Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. AB - High-dose, posttransplantation cyclophosphamide (PTCy) is an effective strategy for preventing graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT). However, the mechanisms by which PTCy modulates alloimmune responses are not well understood. We studied early T cell reconstitution in patients undergoing alloBMT with PTCy and the effects of mafosfamide, a cyclophosphamide (Cy) analog, on CD4(+) T cells in allogeneic mixed lymphocyte reactions (MLRs) in vitro. Patients exhibited reductions in naive, potentially alloreactive conventional CD4(+) T cells with relative preservation of memory CD4(+)Foxp3(+) T cells. In particular, CD4(+)CD45RA( )Foxp3(+hi) effector regulatory T cells (Tregs) recovered rapidly after alloBMT and, unexpectedly, were present at higher levels in patients with GVHD. CD4(+)Foxp3(+) T cells from patients and from allogeneic MLRs expressed relatively high levels of aldehyde dehydrogenase (ALDH), the major in vivo mechanism of Cy resistance. Treatment of MLR cultures with the ALDH inhibitor diethylaminobenzaldehyde reduced the activation and proliferation of CD4(+) T cells and sensitized Tregs to mafosfamide. Finally, removing Tregs from peripheral blood lymphocyte grafts obviated PTCy's GVHD-protective effect in a xenogeneic transplant model. Together, these findings suggest that Treg resistance to Cy through expression of ALDH may contribute to the clinical activity of PTCy in preventing GVHD. PMID- 24225946 TI - SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure. AB - Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice. In a previous study, we showed that SUMO-1 gene transfer substantially improved cardiac function in a murine model of pressure overload induced HF. Toward clinical translation, we evaluated in this study the effects of SUMO-1 gene transfer in a swine model of ischemic HF. One month after balloon occlusion of the proximal left anterior descending artery followed by reperfusion, the animals were randomized to receive either SUMO-1 at two doses, SERCA2a, or both by adeno-associated vector type 1 (AAV1) gene transfer via antegrade coronary infusion. Control animals received saline infusions. After gene delivery, there was a significant increase in the maximum rate of pressure rise [dP/dt(max)] that was most pronounced in the group that received both SUMO-1 and SERCA2a. The left ventricular ejection fraction (LVEF) improved after high dose SUMO-1 with or without SERCA2a gene delivery, whereas there was a decline in LVEF in the animals receiving saline. Furthermore, the dilatation of LV volumes was prevented in the treatment groups. SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients. PMID- 24225945 TI - Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome. AB - Osteoporosis pseudoglioma syndrome (OPPG) is a rare genetic disease that produces debilitating effects in the skeleton. OPPG is caused by mutations in LRP5, a WNT co-receptor that mediates osteoblast activity. WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST). It is unclear whether OPPG patients might benefit from the anabolic action of sclerostin neutralization therapy (an approach currently being pursued in clinical trials for postmenopausal osteoporosis) in light of their LRP5 deficiency and consequent osteoblast impairment. To assess whether loss of sclerostin is anabolic in OPPG, we measured bone properties in a mouse model of OPPG (Lrp5(-/-)), a mouse model of sclerosteosis (Sost(-/-)), and in mice with both genes knocked out (Lrp5(-/-);Sost(-/-)). Lrp5(-/-);Sost(-/-) mice have larger, denser, and stronger bones than do Lrp5(-/-) mice, indicating that SOST deficiency can improve bone properties via pathways that do not require LRP5. Next, we determined whether the anabolic effects of sclerostin depletion in Lrp5( /-) mice are retained in adult mice by treating 17-week-old Lrp5(-/-) mice with a sclerostin antibody for 3 weeks. Lrp5(+/+) and Lrp5(-/-) mice each exhibited osteoanabolic responses to antibody therapy, as indicated by increased bone mineral density, content, and formation rates. Collectively, our data show that inhibiting sclerostin can improve bone mass whether LRP5 is present or not. In the absence of LRP5, the anabolic effects of SOST depletion can occur via other receptors (such as LRP4/6). Regardless of the mechanism, our results suggest that humans with OPPG might benefit from sclerostin neutralization therapies. PMID- 24225947 TI - Protein phosphatase 2A is regulated by protein kinase Calpha (PKCalpha)-dependent phosphorylation of its targeting subunit B56alpha at Ser41. AB - Protein phosphatase 2A (PP2A) is a family of multifunctional serine/threonine phosphatases consisting of a catalytic C, a structural A, and a regulatory B subunit. The substrate and therefore the functional specificity of PP2A are determined by the assembly of the enzyme complex with the appropriate regulatory B subunit families, namely B55, B56, PR72, or PR93/PR110. It has been suggested that additional levels of regulating PP2A function may result from the phosphorylation of B56 isoforms. In this study, we identified a novel phosphorylation site at Ser(41) of B56alpha. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCalpha. We detected a 7-fold higher phosphorylation of B56alpha in failing human hearts compared with nonfailing hearts. Purified PP2A dimeric holoenzyme (subunits C and A) was able to dephosphorylate PKCalpha-phosphorylated B56alpha. The potency of B56alpha for PP2A inhibition was markedly increased by PKCalpha phosphorylation. PP2A activity was also reduced in HEK293 cells transfected with a B56alpha mutant, where serine 41 was replaced by aspartic acid, which mimics phosphorylation. More evidence for a functional role of PKCalpha-dependent phosphorylation of B56alpha was derived from Fluo-4 fluorescence measurements in phenylephrine-stimulated Flp293 cells. The endoplasmic reticulum Ca(2+) release was increased by 23% by expression of the pseudophosphorylated form compared with wild-type B56alpha. Taken together, our results suggest that PKCalpha can modify PP2A activity by phosphorylation of B56alpha at Ser(41). This interplay between PKCalpha and PP2A represents a new mechanism to regulate important cellular functions like cellular Ca(2+) homeostasis. PMID- 24225948 TI - Characterization of intermediate steps in amyloid beta (Abeta) production under near-native conditions. AB - Processing of the amyloid precursor protein (APP) by gamma-secretase results in generation of Abeta peptides of different lengths ranging from 51 to 30 residues. Accumulation of Abeta and in particular Abeta42 is enhanced by familial Alzheimer disease (FAD) causing mutations in APP and is believed to play a pivotal role. The molecular mechanism underlying normal Abeta production, the impact of FAD mutations on this process and how anti-amyloidogenic gamma-secretase modulators (GSMs) cause a selective decrease in Abeta40 and Abeta42 and an increase in shorter Abeta peptides, however, is poorly understood. By using a combined immuno and LC-MS-based assay we identify several major intermediates, i.e. 3- and 4 peptides that line up head to head across the entire APP transmembrane sequence from Abeta51 to Abeta31/Abeta30 and from Abeta49 to Abeta30/31. FAD APP mutations displayed a relative increase in 3- and 4-peptides from Abeta48 to Abeta38 compared with Abeta49 to Abeta37. These findings correlate with an increase in the Abeta42/40 ratio. GSMs caused a decrease in Abeta40 and Abeta42 and an increase in Abeta37 and Abeta38 paralleled by an increase of the intermediates Abeta40-38 and Abeta42-39. Collectively, these data provide a thorough characterization of all intermediate steps in Abeta production in native cell membranes and provide key mechanistic insights to genetic and pharmacological modulation of Abeta generation. PMID- 24225949 TI - In planta mutagenesis of Src homology 3 domain-like fold of NdhS, a ferredoxin binding subunit of the chloroplast NADH dehydrogenase-like complex in Arabidopsis: a conserved Arg-193 plays a critical role in ferredoxin binding. AB - Chloroplast NADH dehydrogenase-like (NDH) complex mediates cyclic electron transport around photosystem I and chlororespiration in angiosperms. The Src homology 3 domain (SH3)-like fold protein NdhS/CRR31 is an NDH subunit that is necessary for high affinity binding of ferredoxin, indicating that chloroplast NDH functions as a ferredoxin:plastoquinone oxidoreductase. However, the mechanism of the interaction between NdhS and ferredoxin is unclear. In this study, we analyzed their interaction in planta by using site-directed mutagenesis of NdhS. In general, binding of ferredoxin to its target proteins depends on electrostatic interaction. In silico analysis predicted the presence of a positively charged pocket in the SH3-like domain of NdhS, where nine charged residues are highly conserved among plants. Systematic alteration of these sites with neutral glutamine revealed that only arginine 193 was required for high NDH activity in vivo. Further replacement of arginine 193 with negatively charged aspartate or glutamate or hydrophobic alanine significantly decreased the efficiency of ferredoxin-dependent plastoquinone reduction by NDH in ruptured chloroplasts. Similar results were obtained in in vivo analyses of NDH activity and electron transport. From these results, we propose that the positive charge of arginine 193 in the SH3-like domain of NdhS is critical for electrostatic interaction with ferredoxin in vivo. PMID- 24225950 TI - Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. AB - PCSK9 (proprotein convertase subtilisin/kexin type 9) is a negative regulator of the hepatic LDL receptor, and clinical studies with PCSK9-inhibiting antibodies have demonstrated strong LDL-c-lowering effects. Here we screened phage-displayed peptide libraries and identified the 13-amino acid linear peptide Pep2-8 as the smallest PCSK9 inhibitor with a clearly defined mechanism of inhibition that has been described. Pep2-8 bound to PCSK9 with a KD of 0.7 MUm but did not bind to other proprotein convertases. It fully restored LDL receptor surface levels and LDL particle uptake in PCSK9-treated HepG2 cells. The crystal structure of Pep2-8 bound to C-terminally truncated PCSK9 at 1.85 A resolution showed that the peptide adopted a strand-turn-helix conformation, which is remarkably similar to its solution structure determined by NMR. Consistent with the functional binding site identified by an Ala scan of PCSK9, the structural Pep2-8 contact region of about 400 A(2) largely overlapped with that contacted by the EGF(A) domain of the LDL receptor, suggesting a competitive inhibition mechanism. Consistent with this, Pep2-8 inhibited LDL receptor and EGF(A) domain binding to PCSK9 with IC50 values of 0.8 and 0.4 MUm, respectively. Remarkably, Pep2-8 mimicked secondary structural elements of the EGF(A) domain that interact with PCSK9, notably the beta-strand and a discontinuous short alpha-helix, and it engaged in the same beta-sheet hydrogen bonds as EGF(A) does. Although Pep2-8 itself may not be amenable to therapeutic applications, this study demonstrates the feasibility of developing peptidic inhibitors to functionally relevant sites on PCSK9. PMID- 24225951 TI - The prion protein modulates A-type K+ currents mediated by Kv4.2 complexes through dipeptidyl aminopeptidase-like protein 6. AB - Widely expressed in the adult central nervous system, the cellular prion protein (PrP(C)) is implicated in a variety of processes, including neuronal excitability. Dipeptidyl aminopeptidase-like protein 6 (DPP6) was first identified as a PrP(C) interactor using in vivo formaldehyde cross-linking of wild type (WT) mouse brain. This finding was confirmed in three cell lines and, because DPP6 directs the functional assembly of K(+) channels, we assessed the impact of WT and mutant PrP(C) upon Kv4.2-based cell surface macromolecular complexes. Whereas a Gerstmann-Straussler-Scheinker disease version of PrP with eight extra octarepeats was a loss of function both for complex formation and for modulation of Kv4.2 channels, WT PrP(C), in a DPP6-dependent manner, modulated Kv4.2 channel properties, causing an increase in peak amplitude, a rightward shift of the voltage-dependent steady-state inactivation curve, a slower inactivation, and a faster recovery from steady-state inactivation. Thus, the net impact of wt PrP(C) was one of enhancement, which plays a critical role in the down-regulation of neuronal membrane excitability and is associated with a decreased susceptibility to seizures. Insofar as previous work has established a requirement for WT PrP(C) in the Abeta-dependent modulation of excitability in cholinergic basal forebrain neurons, our findings implicate PrP(C) regulation of Kv4.2 channels as a mechanism contributing to the effects of oligomeric Abeta upon neuronal excitability and viability. PMID- 24225952 TI - Actin-binding and cell proliferation activities of angiomotin family members are regulated by Hippo pathway-mediated phosphorylation. AB - Whether the Hippo pathway has downstream targets other than YAP and TAZ is unknown. In this report, we have identified angiomotin (Amot) family members as novel substrates of Hippo core kinases. The N-terminal regions of Amot proteins contain a conserved HXRXXS consensus site for LATS1/2-mediated phosphorylation. Phospho-specific antibodies showed that Hippo core kinases could mediate phosphorylation of endogenous as well as exogenous Amot family members. Knockdown of LATS1 and LATS2 endogenously reduced the phosphorylation of Amots detected by the phospho-specific antibodies. Mutation of the serine to alanine within this HXRXXS site in Amot and AmotL2 established that this site was essential for Hippo core kinase-mediated phosphorylation. Wild-type and non-phosphorylated Amot (Amot S175A) were targeted to actin filaments, whereas phospho-mimic Amot (Amot-S175D) failed to be localized with actin. Overexpression of LATS2 caused dissociation of Amot from actin but not Amot-S175A. Mapping of the actin-binding site of Amot showed that serine 175 of Amot was important for the actin-binding activity. Amot S175A promoted, whereas Amot and Amot-S175D inhibited, cell proliferation. These results collectively suggest that the Hippo pathway negatively regulates the actin-binding activity of Amot family members through direct phosphorylation. PMID- 24225953 TI - Novel key metabolites reveal further branching of the roquefortine/meleagrin biosynthetic pathway. AB - Metabolic profiling and structural elucidation of novel secondary metabolites obtained from derived deletion strains of the filamentous fungus Penicillium chrysogenum were used to reassign various previously ascribed synthetase genes of the roquefortine/meleagrin pathway to their corresponding products. Next to the structural characterization of roquefortine F and neoxaline, which are for the first time reported for P. chrysogenum, we identified the novel metabolite roquefortine L, including its degradation products, harboring remarkable chemical structures. Their biosynthesis is discussed, questioning the exclusive role of glandicoline A as key intermediate in the pathway. The results reveal that further enzymes of this pathway are rather unspecific and catalyze more than one reaction, leading to excessive branching in the pathway with meleagrin and neoxaline as end products of two branches. PMID- 24225954 TI - Body fluid exosomes promote secretion of inflammatory cytokines in monocytic cells via Toll-like receptor signaling. AB - Tumor-derived exosomes have been shown to induce various immunomodulatory effects. However, the underlying signaling pathways are poorly understood. Here, we analyzed the effects of ex vivo-derived exosomes on monocytic cell differentiation/activation using THP-1 cells as model. We isolated exosomes from various body fluids such as amniotic fluid, liver cirrhosis ascites, and malignant ascites of ovarian cancer patients. We observed that exosomes were internalized by THP-1 cells and induced the production of IL-1beta, TNF-alpha, and IL-6. Analysis of the signaling pathways revealed a fast triggering of NFkappaB and a delayed activation of STAT3. Pharmacologic and antibody-blocking experiments showed that the initial production of IL-6 was instrumental for subsequent activation of STAT3. Importantly, triggering of cell signaling was not a unique property of tumor exosomes but was also observed with exosomes of noncancerous origin. Exosomal signaling was TLR-dependent as the knockdown of Toll-like receptor 2 (TLR2) and TLR4 blocked NFkappaB and STAT3 activation. Similar results were obtained with TLR-neutralizing antibodies. Exosomes also triggered the release of cytokines from mouse bone marrow-derived dendritic cells or macrophages. This process was MyD88-dependent, further supporting a role of TLR signaling. Our results suggest that exosomes trigger TLR-dependent signaling pathways in monocytic precursor cells but possibly also in other immune cells. This process could be important for the induction of immunosuppressive mechanisms during cancer progression and inflammatory diseases. PMID- 24225955 TI - Structure of soybean serine acetyltransferase and formation of the cysteine regulatory complex as a molecular chaperone. AB - Serine acetyltransferase (SAT) catalyzes the limiting reaction in plant and microbial biosynthesis of cysteine. In addition to its enzymatic function, SAT forms a macromolecular complex with O-acetylserine sulfhydrylase. Formation of the cysteine regulatory complex (CRC) is a critical biochemical control feature in plant sulfur metabolism. Here we present the 1.75-3.0 A resolution x-ray crystal structures of soybean (Glycine max) SAT (GmSAT) in apoenzyme, serine bound, and CoA-bound forms. The GmSAT-serine and GmSAT-CoA structures provide new details on substrate interactions in the active site. The crystal structures and analysis of site-directed mutants suggest that His(169) and Asp(154) form a catalytic dyad for general base catalysis and that His(189) may stabilize the oxyanion reaction intermediate. Glu(177) helps to position Arg(203) and His(204) and the beta1c-beta2c loop for serine binding. A similar role for ionic interactions formed by Lys(230) is required for CoA binding. The GmSAT structures also identify Arg(253) as important for the enhanced catalytic efficiency of SAT in the CRC and suggest that movement of the residue may stabilize CoA binding in the macromolecular complex. Differences in the effect of cold on GmSAT activity in the isolated enzyme versus the enzyme in the CRC were also observed. A role for CRC formation as a molecular chaperone to maintain SAT activity in response to an environmental stress is proposed for this multienzyme complex in plants. PMID- 24225956 TI - Cdc48 chaperone and adaptor Ubx4 distribute the proteasome in the nucleus for anaphase proteolysis. AB - The cell cycle transition is driven by abrupt degradation of key regulators. While ubiquitylation of these proteins has been extensively studied, the requirement for the proteolytic step is less understood. By analyzing the cell cycle function of Cdc48 in the budding yeast Saccharomyces cerevisiae, we found that double mutations in Cdc48 and its adaptor Ubx4 cause mitotic arrest with sustained Clb2 and Cdc20 proteins that are normally degraded in anaphase. The phenotype is neither caused by spindle checkpoint activation nor a defect in the assembly or the activity of the ubiquitylation machinery and the proteasome. Interestingly, the 26S proteasome is mislocalized into foci, which are colocalized with nuclear envelope anchor Sts1 in cdc48-3 ubx4 cells. Moreover, genetic analysis reveals that ubx4 deletion mutant dies in the absence of Rpn4, a transcriptional activator for proteasome subunits, and the proteasome chaperone Ump1, indicating that an optimal level of the proteasome is required for survival. Overexpression of Rpn4 indeed can rescue cell growth and anaphase proteolysis in cdc48-3 ubx4 cells. Biochemical analysis further shows that Ubx4 interacts with the proteasome. Our data propose that Cdc48-Ubx4 acts on the proteasome and uses the chaperone activity to promote its nuclear distribution, thereby optimizing the proteasome level for efficient degradation of mitotic regulators. PMID- 24225958 TI - E-cigarettes: good for children? PMID- 24225957 TI - The crystal structure of shiga toxin type 2 with bound disaccharide guides the design of a heterobifunctional toxin inhibitor. AB - Shiga toxin type 2 (Stx2a) is clinically most closely associated with enterohemorrhagic E. coli O157:H7-mediated hemorrhagic colitis that sometimes progresses to hemolytic-uremic syndrome. The ability to express the toxin has been acquired by other Escherichia coli strains, and outbreaks of food poisoning have caused significant mortality rates as, for example, in the 2011 outbreak in northern Germany. Stx2a, an AB5 toxin, gains entry into human cells via the glycosphingolipid receptor Gb3. We have determined the first crystal structure of a disaccharide analog of Gb3 bound to the B5 pentamer of Stx2a holotoxin. In this Gb3 analog,-GalNAc replaces the terminal-Gal residue. This co-crystal structure confirms previous inferences that two of the primary binding sites identified in theB5 pentamer of Stx1 are also functional in Stx2a. This knowledge provides a rationale for the synthesis and evaluation of heterobifunctional antagonists for E. coli toxins that target Stx2a. Incorporation of GalNAc Gb3 trisaccharide in a heterobifunctional ligand with an attached pyruvate acetal, a ligand for human amyloid P component, and conjugation to poly[acrylamide-co-(3 azidopropylmethacrylamide)] produced a polymer that neutralized Stx2a in a mouse model of Shigatoxemia. PMID- 24225959 TI - Ultrasound hip screening: why bother? PMID- 24225960 TI - Question 1: Is there a role for high-flow nasal cannula oxygen therapy to prevent endotracheal intubation in children with viral bronchiolitis? PMID- 24225961 TI - Towards evidence based medicine for paediatricians. PMID- 24225962 TI - Question 2: Will continuous positive airway pressure reduce the need for ventilation in bronchiolitis? PMID- 24225964 TI - An update on venous thromboembolism in cancer. PMID- 24225965 TI - Joint statement by members of the NCCN Prostate Cancer Guidelines Panel. PMID- 24225966 TI - Treatment of cancer-associated retinopathy with rituximab. AB - Cancer-associated retinopathy (CAR) is a rare autoimmune condition associated with various cancers, causing significant visual impairment. Visual symptoms in CAR may or may not correlate with the extent of systemic disease or its response to chemotherapy, and must be addressed separately from the management of systemic malignancy. Steroids have been the mainstay of CAR therapy. Various immunomodulatory therapies have also been described with varying responses, but the overall visual prognosis remains poor. Rituximab is a monoclonal antibody used in the treatment of non-Hodgkin's B-cell lymphoma and many autoimmune disorders. This case report describes a patient with small cell uterine cancer who initially presented with visual impairment associated with CAR. The patient's deteriorating visual symptoms were successfully halted for an extended, clinically meaningful period with rituximab. PMID- 24225967 TI - Chronic Myelogenous Leukemia, Version 1.2014. AB - The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. A BCR ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months (BCR-ABL1 transcript level <=10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months). PMID- 24225968 TI - Translating genomics in cancer care. AB - There is increasing enthusiasm for genomics and its promise in advancing personalized medicine. Genomic information has been used to personalize health care for decades, spanning the fields of cardiovascular disease, infectious disease, endocrinology, metabolic medicine, and hematology. However, oncology has often been the first test bed for the clinical translation of genomics for diagnostic, prognostic, and therapeutic applications. Notable hereditary cancer examples include testing for mutations in BRCA1 or BRCA2 in unaffected women to identify those at significantly elevated risk for developing breast and ovarian cancers, and screening patients with newly diagnosed colorectal cancer for mutations in 4 mismatch repair genes to reduce morbidity and mortality in their relatives. Somatic genomic testing is also increasingly used in oncology, with gene expression profiling of breast tumors and EGFR testing to predict treatment response representing commonly used examples. Health technology assessment provides a rigorous means to inform clinical and policy decision-making through systematic assessment of the evidentiary base, along with precepts of clinical effectiveness, cost-effectiveness, and consideration of risks and benefits for health care delivery and society. Although this evaluation is a fundamental step in the translation of any new therapeutic, procedure, or diagnostic test into clinical care, emerging developments may threaten this standard. These include "direct to consumer" genomic risk assessment services and the challenges posed by incidental results generated from next-generation sequencing (NGS) technologies. This article presents a review of the evidentiary standards and knowledge base supporting the translation of key cancer genomic technologies along the continuum of validity, utility, cost-effectiveness, health service impacts, and ethical and societal issues, and offers future research considerations to guide the responsible introduction of NGS technologies into health care. It concludes that significant evidentiary gaps remain in translating genomic technologies into routine clinical practice, particularly in efficacy, health outcomes, cost effectiveness, and health services research. These caveats are especially germane in the context of NGS, wherein efforts are underway to translate NGS results despite their limited accuracy, lack of proven efficacy, and significant computational and counseling challenges. Further research across these domains is critical to inform the effective, efficient, and equitable translation of genomics into cancer care. PMID- 24225969 TI - Rapid access to mental health professionals with experience in treating cancer related distress: the American Psychosocial Oncology Referral Helpline. AB - The new quality standard for cancer care established in 2008 by the Institute of Medicine requires that the psychosocial domain be integrated into routine cancer care. The American College of Surgeons Commission on Cancer has incorporated this standard in its accreditation requirements for 1500 cancer centers in the country, to be fully implemented by 2015. Oncology offices and clinics are developing procedures for quickly identifying distressed patients and referring them to appropriate mental health professionals. The American Psychosocial Oncology Society (APOS), the Association of Oncology Social Work, and the Oncology Nursing Society are currently drafting recommendations to assist clinics in complying with accreditation requirements. A critical component of this new quality standard is assuring that those who need mental health services are referred to the appropriate resource. A large disconnect exists in most communities between oncology and mental health professionals because they treat very different patient populations. Therefore, oncology staff may have difficulty identifying mental health professionals for patients in need of psychological help. This step can be simplified by use of the APOS Helpline. This article discusses the unique role of the APOS Referral Helpline in the context of this new era of psychosocial care for patients with cancer. PMID- 24225970 TI - Models of care and NCCN guideline adherence in very-low-risk prostate cancer. AB - NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer. PMID- 24225971 TI - Molecular tumor testing for Lynch syndrome in patients with colorectal cancer. AB - Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, and accounts for 2% to 3% of all colorectal cancers. These tumors are caused by germline mutations of DNA mismatch repair genes, which result in microsatellite instability. Colonic and extracolonic malignancies can occur at a young age, and are often diagnosed at a late stage because of underrecognition of the syndrome. Identifying individuals with LS before the development of these malignancies decreases mortality because of frequent screening and surveillance of colonic and extracolonic cancers. Moreover, family members of these individuals can be tested and begin screening at a young age if appropriate. Classically, Amsterdam criteria and Bethesda guidelines have been used to identify at-risk individuals; however, these tools miss a significant number of cases. As the molecular basis for LS has been clarified, more sophisticated strategies have emerged. Testing all colorectal cancers for loss of mismatch repair proteins, known as universal screening, is a strategy used to identify individuals at risk for LS. This approach has been shown to be more sensitive than previous methods that rely on family history. Implementation of universal tumor testing necessitates a systematic approach to positive results in order to have maximal effect, and could prove to be the most cost-effective approach to reducing cancer mortality in patients with LS. PMID- 24225973 TI - Venous thromboembolic disease. AB - Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer. PMID- 24225974 TI - Venous thromboembolism prevention in cancer outpatients. AB - Venous thromboembolism (VTE) has serious consequences for patients with cancer, including mortality. VTE is preventable with appropriate thromboprophylaxis, but prior public health efforts have focused on prophylaxis in the inpatient setting. However, most VTE events in malignancy currently occur in outpatients. Several recent clinical trials have addressed thromboprophylaxis in the ambulatory setting. Their findings suggest potential benefit, but with significant variation in underlying risk. A risk-adapted approach that incorporates risk of thrombosis, risk of bleeding, and patient preference can target high-risk patients and also allow low-risk patients to avoid prophylaxis. Risk assessment is therefore key to patient selection for outpatient prophylaxis. This article focuses on results of recent trials and updates from major guideline panels, with the intent of providing guidance to clinical providers. PMID- 24225972 TI - Efficacy trial of an Internet-based intervention for cancer-related female sexual dysfunction. AB - The recent NCCN Guidelines for Survivorship recommend systematic evaluation and multidisciplinary treatment of cancer-related sexual dysfunctions. However, most oncology professionals fail to routinely assess sexual problems and lack expertise to treat them. An Internet-based intervention was designed to educate female patients and their partners about cancer-related sexual problems, describe medical treatment options and how to find expert care, and provide self-help strategies. A randomized trial assessed efficacy of the intervention when used as self-help versus the same Web access and 3 supplemental counseling sessions. Survivors of localized breast or gynecologic cancers completed online questionnaires at baseline, posttreatment, and 3- and 6-month follow-up, including the Female Sexual Function Index (FSFI), the Menopausal Sexual Interest Questionnaire (MSIQ), the Brief Symptom Inventory-18 (BSI-18) to assess emotional distress, and the Quality of Life in Adult Cancer Survivors (QLACS) scale. Program evaluation ratings were completed posttreatment. Fifty-eight women completed baseline questionnaires (mean age, 53 +/- 9 years). Drop-out rates were 22% during treatment and 34% at 6-month follow-up. Linear mixed models for each outcome across time showed improvement in total scores on the FSFI, MSIQ, and QLACS (P<.001) and BSI-18 (P=.001). The counseled group improved significantly more on sexuality measures, but changes in emotional distress and quality of life did not differ between groups. Program content and ease of use were rated positively. Research is needed on how best to integrate this intervention into routine clinical practice, and particularly how to improve uptake and adherence. PMID- 24225975 TI - Are new oral anticoagulants ready for use in patients with cancer? AB - Patients with cancer have long been an important and enigmatic part of basic science and clinical research in thromboembolic disease. The reciprocal deleterious effects on outcomes of a cancer diagnosis on patients with thrombosis and a thrombotic event on patients with cancer have been observed and documented for more than a century. Patients with cancer continue to be one of the more difficult populations to manage using the available unfractionated and low molecular-weight heparins and the oral vitamin K antagonists. High rates of failure and bleeding complications have made researchers and practitioners alike seek newer more effective anticoagulation agents. The novel oral direct thrombin and activated factor Xa inhibitors have been shown in large clinical trials to be safe and efficacious in many prophylaxis and treatment settings. However, practitioners who treat patients with cancer should be cautious using these agents until more studies are specifically performed in this thrombophilic patient population. PMID- 24225976 TI - Underinsured patients and the financial fallout of cancer care. PMID- 24225979 TI - SCVA December 2013: update in perioperative medicine. PMID- 24225982 TI - Editor's note. PMID- 24225980 TI - Extenders of cognition. PMID- 24225983 TI - Psychology and primary care: Evolving traditions. AB - The involvement of psychology and psychologists in primary health care is based upon patient care needs which suggest that upward of 60% of all visits to primary care physicians' offices are psychological in nature. Psychologists have a strong tradition of providing primary health care to medically ill patients and as long term members of the health care team. The wide array of cost-effective patient care services provided by psychologists is discussed. Present APA initiatives in primary health care are presented, along with descriptions of the manuscripts in this special issue of theJournal of Clinical Psychology in Medical Settings focusing on primary health care. PMID- 24225984 TI - Building a primary care discipline: Notes from a psychologist in family medicine. AB - Psychologists of a variety of emphases have actively participated in the growth of family medicine as an academic discipline. Rather than simply collaborate, they have shaped the very nature of the field. This paper describes a number of contributions from psychologists in family systems and educational arenas. In particular, physician-psychologist collaborative work is highlighted. PMID- 24225985 TI - Teaching psychological knowledge and skills to family physicians. AB - Psychological problems (e.g., anxiety, depression, substance abuse) are prevalent in primary care medical settings. Family physicians (FPs) treat more patients than any other primary care medical specialists. Thus, FPs can play an extremely important role in providing psychological services to their patients. In contrast to other specialists (e.g., internists, obstetricians), FPs are required to complete behavioral science training in their residencies. In this paper, we describe standard undergraduate, graduate, and postgraduate training of FPs. We present our unique program for teaching psychological principles and skills to family practice residents at the University of Kansas Medical Center. And finally, we introduce an instrument, the Interview Rating Scale (IRS), for evaluating the interviewing skills of physicians and residents. PMID- 24225986 TI - Primary health care for women: What is it and who provides it? AB - Recent federal policy has highlighted historically underrecognized women's health issues. Women comprise the majority of the population, especially the elderly. Women's health care needs, utilization patterns, and outcomes vary from those of men, and often among each other. Primary health care services for women are multidisciplinary and emphasize prevention, education, and early intervention as well as treatment. Psychologists and other primary health care providers can collaborate to provide their services in a cost-effective manner that optimizes quality of care and comprehensive health care. PMID- 24225987 TI - Domestic violence in primary care: The psychologist's role. AB - This paper highlights the difficulties facing medical and mental health professionals in helping families in which there is violence. Emphasis is placed on how domestic violence presents in primary care medical settings. Physician and patient characteristics that interfere with domestic violence detection are reviewed. A role is outlined for psychologists in primary care settings to facilitate detection and treatment. Facilitative efforts include educating physicians through collaboration and serving as an on-site resource for information and consultation. PMID- 24225988 TI - The detection and management of mental health disorders in pediatric primary care. AB - We reviewed the literature on the detection and management of mental health disorders within the context of pediatric primary care. Pediatricians have displayed a low sensitivity and high specificity in research investigating the detection of mental health impairment in children. Active management efforts characterize approaches to identified cases with more recently trained primary care pediatricians displaying a wider range of skills in managing mental health disorders. Few efforts have been made by pediatric psychologists to develop strategies for enhancing detection rates and management or to empirically evaluate the integration of pediatric psychology services into the primary care context. A conceptual model of factors influencing detection rates and ongoing management of mental health disorders within pediatric primary care is presented. Recommendations are made for more direct involvement of pediatric psychologists within the primary care context. PMID- 24225989 TI - Evaluating pediatric psychology consultation services in a medical setting: An example. AB - We examined the nature of referrals to a health center-based pediatric psychology service from 1990 to 1993 and assessed the satisfaction of health professionals with these services. Archival evaluation of 1467 records showed that over half of the consultation requests came from general pediatrics, pediatric neurology, and surgical services and that 70% of the psychological services were delivered on an outpatient basis. The most frequent referrals were for cognitive/neuropsychological evaluation and externalizing behavior problems. Pediatric psychology trainees were involved in 94% of the consultations. Survey of health professionals (n = 143) indicated very high overall satisfaction with the quality of services delivered. Presenting problems yielding the greatest likelihood for future consultation requests were behavior problems, child abuse, coping with illness, and depression/suicide. Results are discussed in the context of previous evaluations of pediatric psychology services and recommendations for future evaluation research. PMID- 24225990 TI - New directions for the education of clinical psychologists: The primary care setting, the VA's PRIME program, and the in-depth generalist model. AB - As part of this special issue on psychology in primary care settings, we describe the Department of Veterans Affairs' (VA's) new approach to education for practice in the primary care setting and we concurrently address some general issues related to the education of clinical psychologists for practice in this setting. In this article we argue that the primary care psychologist, in parallel with the generalist in medicine, must have a strong generic background in clinical psychology in order to gain the broad range of clinical skills necessary to function effectively as an "in-depth generalist" (IDG) who is capable of addressing the variety of psychological issues that emerge in the primary care setting. The IDG model of professional practice, which we believe is best suited for primary care/managed care settings, requires extensive training in generic clinical skills and increased time devoted to its implementation at both the predoctoral and the postdoctoral levels. PMID- 24225991 TI - A commentary on high-dose enzyme replacement therapy attenuates cerebroventriculomegaly in a mouse model of mucopolysaccharidosis type II. PMID- 24225992 TI - Differences in carrier frequency between mothers of Duchenne and Becker muscular dystrophy patients. AB - Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked inherited muscular disorders caused by mutations in the dystrophin gene. Two-thirds of DMD cases are thought to be caused by inheritance from carrier mothers and this study aimed to clarify and compare the carrier frequency of mothers of DMD and BMD patients according to the mutation type. We included 139 DMD and 19 BMD mothers. Of these, 113 patients (99 DMD and 14 BMD) and 13 patients (12 DMD and 1 BMD) had deletions and duplications of one or more exons, respectively. Small mutations, including nonsense mutations, small deletions/insertions and splice site mutations, were identified in 32 patients (28 DMD and four BMD). The overall carrier frequency for BMD mothers was significantly higher than for DMD (89.5% vs 57.6%, P<0.05), probably as BMD patients can leave descendants. The carrier frequency tended to be lower in mothers of DMD patients with deletion mutations than with duplications and small mutations (53.5%, 66.7% and 67.9%, respectively). It was suggested that de novo mutations are more prevalent for deletions than other mutations. This is the first report to analyze the carrier frequency according to mutation type. PMID- 24225994 TI - Computer simulation of single-ion trajectories in paul-type ion traps. AB - The computer simulation of single-ion trajectories using a number of computer programs is described together with associated theory. The programs permit calculation of ion trajectories while the ion is subjected to collisions with buffer gas of variable pressure, resonance excitation in any of three modes, and static or ramped DC and radiofrequency levels. Initially, the programs were designed for the calculation of ion trajectories in a quadrupole ion trap. The programs now permit such calculations for ions confined in traps having electrodes shaped to include percentages of hexapole and octupole components in the electric field as well as electrode surface geometries for which there is no closed-form expression. The Langevin collision theory is reviewed and a theoretical treatment of the multipole trap is presented. PMID- 24225993 TI - A new mutation in the C-SH2 domain of PTPN11 causes Noonan syndrome with multiple giant cell lesions. AB - Noonan syndrome (NS), an autosomal dominant multisystem disorder, is caused by the dysregulation of the RAS-MAPK pathway and is characterized by short stature, heart defects, pectus excavatum, webbed neck, learning problems, cryptorchidism and facial dysmorphism. We here present the clinical and molecular characterization of a family with NS and multiple giant cell lesions (MGCLs). The proband is a 12-year-old girl with NS and MGCL. Her mother shows typical NS without MGCL. Whole-exome sequencing of the girl, her mother and her healthy maternal grand parents revealed a previously unobserved mutation in exon 5 of the PTPN11 gene (c.598 A>T; p.N200Y), transmitted from the mother to the proband. As no other modification in the RAS-MAPK pathway genes as related to Rasopathies was detected in the proband, this report demonstrates for the first time that a unique mutation affecting this, otherwise unaffected signaling route, can cause both NS and NS/MGCL in the same family. This observation further confirms that NS/MGCL is not a distinct entity but rather that MGCL represents a rare complication of NS. Moreover, the localization of the p.N200Y mutation suggests an alternative molecular mechanism for the excessive phosphatase activity of the PTPN11-encoded protein. PMID- 24225995 TI - A method of increasing the sensitivity for laser desorption in an ion trap mass spectrometer. AB - Laser desorption in an ion trap mass spectrometer shows significant promise for both qualitative and trace analysis. In this work, we explore various combinations of time-varying DC and radiofrequency (RF) fields in order to optimize laser-generated signals. By judicious choice of timing between the laser desorption pulse and the rise in the applied RF trapping potential, we observed over an order of magnitude enhancement in the trapped ion signal. This new method for laser desorption has enabled us to observe mass spectra of many compounds (e.g., pyrene, dichlorobenzene, and ferrocene) that are barely detectable using previous laser desorption methods. Effects of laser timing and the magnitude of the steady-state RF potential are discussed. PMID- 24225996 TI - Selective detection of phosphopeptides in complex mixtures by electrospray liquid chromatography/mass spectrometry. AB - A mass spectrometry-based method that does not involve the use of radiolabeling was developed for selective detection of phosphopeptides in complex mixtures. Mixtures of phosphorylated and nonphosphorylated peptides at the low picomole level are analyzed by negative ion electrospray liquid chromatography/mass spectrometry using C-18 packed fused-silica columns (<=320-MUm i.d.). Peptides and phosphopeptides in the chromatographic eluant undergo collision-induced dissociation in the free-jet expansion region prior to the mass analyzing quadrupole. Using relatively high collisional excitation potentials, phospho|peptides containing phosphoserine, phosphothreonine, and phosphotyrosine fragment to yield diagnostic ions at m/z 63 and 79 corresponding to PO2 (-); and PO3 (-), respectively. Chromatographic peaks containing phosphopeptides are indicated where these diagnostic ions maximize. The highest sensitivity for phosphopeptide detection is obtained using selected-ion monitoring for m/z 63 and 79. Full-scan mass spectra that exhibit the diagnostic phosphopeptide fragment ions, together with pseudomolecular ions, may be obtained by stepping the collisional excitation potential from a high value during the portion of each scan in which the low-mass-to-charge ratio diagnostic marker ions are being detected to a lower value while the upper mass-to-charge ratio range is being scanned. Good sensitivity for phosphopeptide detection was achieved using standard trifluoroacetic acid containing mobile phases for reversed-phase high performance liquid chromatography. Data illustrating the selectivity and sensitivity of the approach are presented for mixtures of peptides and phosphopeptides containing the three commonly phosphorylated amino acids. PMID- 24225997 TI - Comparison of the orders of gas-phase basicities and ammonium ion affinities of polyethers by the kinetic method and ligand exchange technique. AB - The orders of relative gas-phase basicities and ammonium ion affinities of a series of polyethers obtained by application of the kinetic method and ligand exchange technique are compared to evaluate the discrepancies of results between the two techniques. The order of gas-phase basicities determined by the ligand exchange technique in a quadrupole ion trap agrees with the order established previously by Kebarle using equilibrium methods in a high-pressure mass spectrometer. The order obtained by the kinetic method in a triple quadrupole mass spectrometer varies for the ranking of one polyether (12-crown-4), and this discrepancy is attributed to a difference in the rates of the competing dissociation pathways from the triethylene glycol dimethyl ether/12-crown4 proton bound adduct, owing to a substantial variation in the flexibilities of these two ethers. For the order of gas-phase ammonium ion affinities, the kinetic method results agree overall with the ligand exchange results; however, the order of ammonium ion affinities for tetraethylene glycol dimethyl ether and 15-crown-5 could not be differentiated by the ligand exchange method because of the rapidity of ammonium ion transfer between the two polyethers in both directions. PMID- 24225998 TI - Gas-phase acidities of diols. AB - The gas-phase acidities of several alpha, omega-alkanediols were measured with the equilibrium method in an ion cyclotron resonance spectrometer. The values obtained imply cyclization of the structures via an intramolecular hydrogen bond. The results are in quantitative disagreement with those obtained by the method of dissociation of the excited dimer species; care must be used in applying that method to ensure that all of the criteria for relating kinetics to equilibria are met. PMID- 24225999 TI - Ion formation processes in the afterpeak time regime of pulsed glow discharge plasmas. AB - The formation of ions following the termination of power in a pulsed glow discharge ion source is investigated. The populations of ionized species containing sputtered atoms M(+), M 2 (1) :, and MAr(+) are observed to maximize after the termination of discharge power. Collisions involving sputtered atoms and metastable argon atoms, Penning and associative ionization, are considered to be responsible for the formation of ions in the discharge afterpeak time regime. The domination of these ion formation processes during the afterpeak time regime is supported by the results from investigations of discharge operating parameters, metastable argon atom quenching, and ion kinetic energy distributions. PMID- 24226000 TI - Inductively coupled plasma mass spectrometry with an electrically floating sampling interface. AB - In conventional inductively coupled plasma mass spectrometry devices, the sampler and skimmer are grounded. In this work, modest DC voltages (+ 10 to + 50 Vl are applied to either (or both) sampler and skimmer. Alternatively, the skimmer is biased, and the sampler is merely left floating. The latter arrangement improves sensitivity for Co(+) by sixfold, provides nearly the same molar sensitivity for CO(+), Rh(+), and Ho(+), and extends the upper end of the linear dynamic range to approximately 100 ppm. These changes to the interface do not affect the background perceptibly. The relationship between applied potential and the potential actually measured on the sampler and skimmer is also discussed. PMID- 24226001 TI - Networking mass spectrometer data systems for improved productivity and electronic archiving of data. AB - Several Finngan-MAT mass spectrometer data systems were networked together to achieve the following two primary objectives: (1) to allow access to mass spectrometry data and data processing functions from remote locations without affecting simultaneous data acquisition at the instruments, and (2) to electronically archive mass spectrometry data at a central location on a high capacity, fast-access device that allows rapid retrieval of archived data for all data processing operations at all locations. UNIX workstations, IBM PC/AT compatible computers, and Data General Nova minicomputers were connected via Ethernet interfaces to allow rapid data transfer among all systems as well as X Windows access to UNIX-based systems. Bridging techniques were used to isolate possible high-traffic areas of the network and to enable security measures for adequate protection of files. Additionally, serial connections were made through a Northern Telecom phone system to provide remote terminal access to the Data General Nova-based systems. Use of these connectivity techniques significantly improved productivity by allowing retrieval, processing, and printing of data from remote locations, such as office areas, without affecting data acquisition, processing, and printing performed simultaneously at the instruments. For archival purposes, data files are electronically stored on high-capacity magneto optical disks for rapid retrieval. A highcapacity fixed disk is also available for centralized temporary data file storage. A Digital Equipment Corporation DECstation 2100 UNIX workstation was used as the file server for centralized data storage while being simultaneously utilized as the data system computer for one of the mass spectrometers. Utilization of this UNIX-based file server system in conjunction with Ethernet connectivity techniques provides a centralized, rapid access, high-capacity, cost- and space-efficient method for electronic archival of mass spectrometry raw data recorded at all of the instruments. PMID- 24226002 TI - High Efficiency Photo-Induced Dissociation of Precursor Ions in a Tandem Time-of Flight Mass Spectrometer. AB - High efficiency photo-induced dissociation (PID) has been demonstrated in a tandem time-of-flight mass spectrometer. This instrument focuses isomass ion packets to temporal and spatial dimensions similar to those of the focused laser pulses from a high power excimer laser. This high density overlap of photons and ions yields highly efficient fragmentation and also provides high resolution selection of specific precursor ion mass-to-charge ratio values. Using 193 nm photon excitation of the molecular ion of bromobenzene (m/z = 1561, fragmentation, collection, and PID efficiencies af 79%, 132%, and 104%, respectively, were obtained. Characteristic fragmentations of toluene, nitrobenzene, acetophenone, triethylamine, N,N-diethylformamide, N methylacetamide, and cyclohexene have also been demonstrated. PMID- 24226003 TI - Genetic analysis of methionine-rich storage protein accumulation in maize. AB - Experiments were conducted to determine the chromosomal location of the gene conditioning overproduction of a methionine-rich, 10-K zein in maize kernels of line BSSS53. In addition, the chromosomal location of the structural gene encoding the overproduced protein was determined. Whereas the structural gene, designated Zps10/(22), was found to be located on the long arm of chromosome 9 near the centromere, the locus regulating overproduction of the zein protein was mapped to the short arm of chromosome 4. This regulatory gene has been designated Zpr10/(22). Regulation of 10-K zein production by Zpr10/(22) is, therefore, via a trans-acting mechanism. PMID- 24226004 TI - Inheritance of plastids in interspecific hybrids of blue spruce and white spruce. AB - Chloroplast DNA (cpDNA) was purified from blue spruce (Picea pungens Engelm.) and white spruce [P. glauca (Moench) Voss], and was digested with several different restriction endonucleases. Restriction fragment length polymorphisms (RFLPs) were identified that differentiated the cpDNA of both species. Intraspecific conservation of the RFLPs that differentiated each species was confirmed by examining trees from across the natural range of each species. Ten F1 hybrids were examined, and the cpDNA from each showed the banding pattern of the paternal species. Cloned Petunia cpDNA containing part of the rbcL gene hybridized to polymorphic bands, while a cloned maize mtDNA probe of the coxII gene failed to hybridize to any band. PMID- 24226005 TI - Selection strategies for developing smooth bromegrass cell wall ideotypes. AB - A random sample of 80 families of the B8HD smooth bromegrass (Bromus inermis Leyss.) population were tested in three environments for forage yield and cell wall constituents. Expected progress from one cycle of family selection was computed for single-trait selection and multiple-trait restricted selection. Expected gains were compared to desired goals and actual results from one cycle of phenotypic selection. Desired goals were: Model I = reduced lignin and cellulose, with increased hemicellulose, resulting in no change in cell wall content; Model II = reduced lignin and cellulose with no change in hemicellulose; or Model III = reduced lignin, cellulose, and hemicellulose. Single-trait selection for high hemicellulose in first harvest or low cellulose in second harvest had the best expected responses, of any single trait, for Model I. Possible undesirable effects of selection for low cellulose would be a reduction in forage yield potential. Multiple-trait restricted selection was judged to be more effective, with responses all in the desired direction, by specifying increased hemicellulose in index development. Selection in second harvest was expected to have similar responses as first harvest, except for a greater increase in forage yield. Development of Models II or III is expected to be difficult due to a negative correlation estimate between first and second harvest cell wall concentration. PMID- 24226006 TI - Control of tissue culture response in wheat (Triticum aestivum L.). AB - The ability of immature embryos of wheat (Triticum aestivum L.) to respond to tissue culture has been shown to involve the group 2 chromosomes. The available group 2 ditelosomic and nullisomic-tetrasomic lines of 'Chinese Spring' wheat were used to determine the chromosome arm location and chromosome dosage effect associated with the expression of tissue culture response (TCR). Significant differences were found between the aneuploid lines and the euploid control for the expression of both regenerable callus formation and callus growth rate. A model is proposed suggesting that a major TCR gene is located on 2DL and that 2AL and 2BS possess minor TCR genes. Furthermore, a major regulatory gene controlling the expression of TCR genes may be located on chromosome 2BL. PMID- 24226007 TI - Inheritance of two endosperm protein loci in rice (Oryza sativa L.). AB - Previous studies indicated two types of phenotypic protein markers as two minor bands of SDS-PAGE for rice storage protein. A variant derived from a Pakistani variety, Dular, was found to show a mobility variant with Band 11, a relatively faster-moving band as compared to Band 10, while most of the other cultivated rices exhibited Band 10 at a molecular weight of around 100-110 K. Band 11 was also observed in several wild rice species. How this variant occurred is not known. Another marker is characterized by the presence of either Band 56 (slower migrating band) or Band 57 (faster-migrating band) in most cultivars at a molecular weight of about 28-27 K. Most indica varieties developed in Taiwan have Band 57 and japonica varieties have Band 56. Genetic analysis of F1, F2 and F3 seeds from interstrain crosses indicated that Band 10 versus Band 11 and Band 56 versus Band 57 are due to codominant alleles at two loci. Tests of independent inheritance between these two loci (Band 10/11 versus Band 56/57) indicated that there is no linkage between them. Both of these two protein loci encode for endosperm proteins and mostly belong to the minor polypeptide subunits of the glutelin fraction of rice seed proteins. Studies on reciprocal crosses indicate dosage effects as exhibited in band patterns. Variations in band intensity were frequently observed when the maternal genotype was different. PMID- 24226008 TI - Genetic control of linolenic acid concentration in seed oil of rapeseed (Brassica napus L.). AB - Results from a diallel mating of two rapeseed lines with distinctly different linolenic acid concentration show that this trait is mainly under control of nuclear genes of the embryo. However, significant differences in reciprocal F1, BC1 and BC2 indicate maternal control, which is realized by interaction between maternal genotype and nuclear genes of the embryo. Additionally, temperature exerts considerable influence on the degree of maternal control. Since no reciprocal differences are detectable in F2, cytoplasmic factors seem not to be involved in the inheritance of linolenic acid concentration. Hypotheses on the physiological nature of maternal control of this trait are discussed. PMID- 24226009 TI - A proposal to improve the efficiency of index selection by "rounding". AB - This paper describes a rounding procedure to improve the efficiency of index selection. The procedure involves performing canonical variate analysis on the phenotypic and genotypic variances of a group of traits estimated from a progeny test experiment. The eigenvectors corresponding to the significant eigenvalues are used to transform the original traits into a set of independent variables. The selection index is then constructed based on the new set of variables. The efficiency of the new index is expected to be improved by rounding off the variables associated with the insignificant eigenvalues. PMID- 24226010 TI - Species relationship in the Pennisetum gene pool: enzyme polymorphism. AB - Variation in leaf esterases (EST), 6-phosphogluconate dehydrogenase (PGD), shikimate dehydrogenase (SKDH), leucine aminopeptidase (AMP), phosphoglucomutase (PGM) and malate dehydrogenase (MDH) is reported in the Pennisetum gene pool. In the primary gene pool, polymorphism for EST, AMP, SKDH was very high, as compared to the near-monomorphic isozymes of PGD. Two loci controlling leaf esterases Est 1 and Est-2, were identified in the primary gene pool. Differences in allelic frequency distribution of the polymorphic Est-1 locus occur between the cultivated and wild pearl millet. The prevalent alleles of Est-1 are absent in P. purpureum Schumach (secondary gene pool). A monomorphic band of the alpha esterase-specific Est-2 locus was identified in most of the secondary gene pool accessions, P. squamulatum Fresen and an accession of P. pedicellatum. SKDH and EST revealed differences between most of the tertiary gene pool species. By contrast, a PGD zymogram was prevalent in several species of different sectional taxa. Gene duplication for PGD isozymes occurs in the diploid species, P. ramosum, of the tertiary gene pool. Heterodimers of PGD and EST were observed in the hybrid between pearl millet and P. squamulatum, whereas a monomeric structure characterized SKDH and AMP. PMID- 24226011 TI - Allozyme diversity in wild Phaseolus vulgaris: further evidence for two major centers of genetic diversity. AB - Allozyme analysis was performed on 83 wild Phaseolus vulgaris accessions, representing a wide geographical distribution from Mesoamerica to Argentina, to determine levels of genetic diversity and geographic patterns of variability at nine polymorphic isozyme loci. The collection can be divided into two major groups, one consisting of accessions from Mexico, Central America, Colombia and Peru, and the other consisting of accessions from Peru and Argentina. One accession from northern Peru is distinct from the two major groups, and may delineate a transition zone between the two divergent groups. The level of genetic diversity within wild P. vulgaris (Ht=0.132) is comparable with those found in other Phaseolus species. There was no significant within-accession gene diversity (Hs=0.006); however, there is a moderate level of genetic diversity (Dst=0.126) between accessions. Our results are consistent with previous studies on the genetic diversity of wild P. vulgaris using phaseolin, the major seed storage protein of beans. PMID- 24226012 TI - Triple hybridization with cultivated barley (Hordeum vulgare L.). AB - A crossing programme for trispecific hybridization including cultivated barley (Hordeum vulgare L.) as the third parent was carried out. The primary hybrids comprised 11 interspecific combinations, each of which had either H. jubatum or H. lechleri as one of the parents. The second parent represented species closely or distantly related to H. jubatum and H. lechleri. In trispecific crosses with diploid barley, the seed set was 5.7%. Crosses with tetraploid barley were highly unsuccessful (0.2% seed set). Three lines of diploid barley were used in the crosses, i.e. 'Gull', 'Golden Promise' and 'Vada'. Generally, cv 'Gull' had high crossability in crosses with related species in the primary hybrid. It is suggested that 'Gull' has a genetic factor for crossability not present in cv 'Vada' and cv 'Golden Promise'. One accession of H. brachyantherum used in the primary hybrid had a very high crossability (seed set 54.7%) in combination with cv 'Vada' but no viable offspring was produced. In all, two trispecific hybrids were raised, viz. (H. lechleri x H. brevisubulatum) x 'Gull' (2n=7-30) and (H. jubatum x H. lechleri) x 'Gull' (2n=20-22). The first combination invariably had a full complement of seven barley chromosomes plus an additional chromosome no. 7, but a varying number of chromosomes (19-22) of the wild-species hybrid. The second combination had a full set of barley chromosomes. The meiotic pairing was low in both combinations. PMID- 24226013 TI - Inheritance of photoperiod-induced flowering in three photoperiodic lines of Aeschynomene americana L. AB - Induction of flowering by photoperiod was studied in the parental, F1, F2, and reciprocal backcross generations of crosses between three photoperiod-responsive Aeschynomene americana L. lines. Generation means appeared additive. Analysis with Mather and Jinks' scaling tests showed little or no epistasis and indicated that an additive-dominance model was adequate. Partitioning components of variation revealed that nearly all variation was additive genetic with dominance and environmental variation negligible. An additive genetic model with two loci, each with two alleles and all alleles having equal net effect, was tested using Power's partitioning method. Results demonstrated that the model fit the data and that there is a major additive genetic system controlling flowering in these crosses, with minor genetic and environmental influences present. Selection for flowering at a desired day length should be feasible. PMID- 24226014 TI - Haploid transformation in Brassica napus using an octopine-producing strain of Agrobacterium tumefaciens. AB - Microspore-derived embryos of Brassica napus were transformed using the disarmed octopine-producing LBA4404 strain of Agrobacterium tumefaciens containing the binary vector pBin19. Octopine-producing strains have previously been reported to be ineffective in transforming Brassica. Four actively growing yellow/ green sectors were selected from the embryos on 50 mg/l kanamycin and plants regenerated. Analysis for NPT-II activity in these young plants initially indicated no expression of the bacterial NPT-II gene. The plants were nevertheless grown to maturity, selfed and S1 seed was collected. Three of the S1 plants produced microspores which were from 4 to 20 times more tolerant to kanamycin than the original parent. Southern analysis revealed that one plant (EC 1) had a single site of insertion and the other two plants (EC-2 and EC-6) had two sites of insertion with sequence homology to the bacterial NPT-II gene. Microspores from the EC-2 and EC-6 transgenics produced embryos on approximately five times the level of kanamycin tolerated by microspores from untransformed plants, while the EC-1 transgenic produced microspores with more than 20 times the tolerance to kanamycin. Analysis of S1 progeny of the EC-1 transgenic indicated that 100% of the progeny exhibited the trait through both Southern analysis and by expressing tolerance to kanamycin in microspore-derived embryos. PMID- 24226015 TI - In vitro culture of Cucumis sativus L. : 7. Genes controlling plant regeneration. AB - The ability to regenerate plants from leaf explants has been tested for three highly inbred cucumber lines (B, G, S), their reciprocal hybrids, F2 and BC1 generations. The lines differed from each other in their regenerating ability, which was expressed by the percentage of explants regenerating embryoidal callus and mean number of plantlets per plant. Thus, the lines could be classified as frequently (B), intermediately (G) or occasionally regenerating ones (S). There were no reciprocal cross differences in the regeneration. It was found that the intermediately and intensively regenerating lines contain two pairs of dominant genes responsible for plant regeneration, characterized by complementary and probably additive interaction. The frequently regenerating line differed from the intermediately regenerating in the effect of one gene. It is supposed that the above-mentioned genes belong to three different loci. The ability to regenerate plants from leaf expiants had high heritability. PMID- 24226016 TI - Genetic improvement of pyrethrum : 4. Selective divergence, heterosis and potential hybrid clones. AB - Pyrethrum (Chrysanthemum cinerariefolium), an important paramedicinal plant is a potential source of pyrethrins, which have a long history of safe uses against mosquito larvae - a carrier of malarial parasite. It was introduced in India from Kenya in 1931. Considerable genetic diversity has been generated over the years. Repeated clonal selection could lead to isolation of a number of divergent clones representing selective divergence. Planned hybridization among some of the chosen clones could further enlarge the spectrum of variation as measured by multivariate analyses (D(2)-statistic and canonical analysis). The resulting hybrids manifested a variable degree of heterosis which was found to be, by and large, positively associated with the degree of divergence between the two constituent parents of a hybrid. However, the choice of the potential hybrid clone(s) for commercial exploitation was most viable when parents for hybridization were short-listed on the basis of parental divergence coupled essentially with per se performance for specific traits. The latter criterion assumes greater significance since low x low or medium x low parental hybrids also tended to register high heterosis for both the pyrethrins content and yield. Four hybrids: 234xL, 8xL, 326*395 and 319xL were identified to be the most promising for clonal selection. PMID- 24226017 TI - Use of restriction fragment length polymorphism to fingerprint beets at the genotype and species levels. AB - cDNA probes have been used to assess genetic variation in beet using hybridisation techniques that detect restriction fragment length polymorphism. Probes have been identified which differ in the levels of variation that they can detect (i) within closely related genetic material of sugar beet, and (ii) between sugar beet and a taxonomically distant Beta species. PMID- 24226018 TI - An attempt to elucidate the origin of cultivated soybean via comparison of nucleotide sequences encoding glycinin B4 polypeptide of cultivated soybean, Glycine max, and its presumed wild progenitor, Glycine soja. AB - Nucleotide sequences of cDNAs encoding soybean glycinin B4 polypeptide were compared for three soybean cultivars and two introductions of wild soybean, G. soja. For three G. max cultivars, only two nucleotide substitutions were found, while G. max and G. soja nucleotide sequences had four substitutions. These data give added proof that G. max originated from G. soja. On the other hand, the time required for the accumulation of four nucleotide substitutions (calculated from the parameters of 11S globulin molecular evolution) appeared to be longer than the duration of the soybean domestication period. PMID- 24226019 TI - Ecotypes and genetic divergence among sympatrically distributed populations of Hordeum vulgare and Hordeum spontaneum from the xeric region of Jordan. AB - The progeny of paired samples of Hordeum vulgare L. and Hordeum spontaneum C. Koch, collected from Jordan's xeric region was used in this study. Statistical analyses of seven easily measured morphometric traits were used to elucidate the relationships and distances between populations of both species, to detect any ecogeographical races, and to study the interrelationships and adjustments in the morphometric traits under study. Flag leaf area and plant height were the two most important discriminating variables which totally separated Hordeum vulgare from Hordeum spontaneum and accounted for 85.3% of total phenotypic variance in the collection. Cluster analysis indicated that the level of divergence among populations of both species was considerably different. Populations of Hordeum vulgare clustered at a maximum Euclidean distance of 2.08, while the maximum distance at which populations of Hordeum spontaneum clustered was 1.49. Three ecotypes each of Hordeum vulgare and Hordeum spontaneum were identified. These ecotypes corresponded to the environmental range of the collection sites. The interrelationships between the seven morphometric traits were adjusted in different ways as revealed by the principal components analysis. Sampling from the different clusters identified in this analysis is expected to increase the allelic diversity for selection and breeding purposes. PMID- 24226020 TI - Paternal inheritance of plastids in Medicago sativa. AB - Plastids are plant cellular organelles that are generally inherited from the maternal parent in the angiosperms. Many species exhibit biparental inheritance of plastids, but usually with a predominantly maternal influence. In contrast to this, we report strong paternal inheritance of plastids in reciprocal crosses of alfalfa, Medicago sativa, by following restriction fragment length polymorphisms for plastid DNA in two normal green plastids. Mitochondrial inheritance remained exclusively maternal. PMID- 24226021 TI - Evidence for cytoplasmic control of in vitro microspore embryogenesis in the anther culture of wheat (Triticum aestivum L.). AB - Anthers were cultured from two sets of seven lines of hexaploid wheat (Triticum aestivum L.) with different cytoplasms, the euplasmic nucleus donors, 'Siete Cerros 66' and 'Penjamo 62', as well as their six alloplasmic lines derived from wild relative species of the genera Triticum and Aegilops. Significant cytoplasmic and nuclear effects but no cytoplasmic-nuclear interaction were found for embryogenic anther response, with the best performance of 'Penjamo 62' in Ae. kotschyi cytoplasm. Plant regeneration was not affected significantly by the cytoplasmic background of the lines cultured. The possible genetic implications of the observed cytoplasmic and nuclear influences on the in vitro haploid induction of wheat are discussed. PMID- 24226022 TI - Chromosomal location of genes controlling heat shock proteins in hexaploid wheat. AB - The low molecular weight heat shock protein (HSP) profiles of the hexaploid wheat cultivar "Chinese Spring" and its ditelosomic series were characterized by isoelectric focusing polyacrylamide gel electrophoresis of denatured in vivo radiolabeled proteins. Comparisons of the ditelosomics (DTs) to the euploid "Chinese Spring" enabled the assignment of genes controlling 9 of the 13 targeted HSPs to seven chromosome arms. There did not appear to be a genome-specific action in the regulation of expression of these HSPs. There did appear to be a higher frequency of controlling genes within homoeologous DT lines 3, 4 and 7. Significant variation in protein quantity was evident among the DT lines for some HSPs, while other HSPs were remarkably stable in their expression across all DTs examined. The results are useful in identifying specific DT lines for the investigation of HSP functions in hexaploid wheat. PMID- 24226023 TI - Nuclear genes affecting albinism in wheat (Triticum aestivum L.) anther culture. AB - Inheritance of the ability to respond in wheat anther culture was studied from 6*2 reciprocal crosses between six varieties with high and two varieties with low capacity for green plant formation and their parents, replicated in two environments. Effects of genotypes dominated embryo formation and percentages of green plants, accounting for 78.4% and 85.4% of total variation, respectively, while smaller genetic effects were indicated for regeneration. Nuclear genes could explain almost all the genotype effects in this material. Embryo formation showed heterosis over high parent for 5 of the 12 hybrids, while percentages of green plants from the hybrids were intermediate to the parents. General Combining Ability (GCA) could explain 78.8% of the variation for embryo formation among the hybrids, whereas differences in percentage of green plants were dominated by Specific Combining Ability (SCA), accounting for 67.9% of hybrid variation. A positive correlation (r=0.81(**)) was observed between the genetic capacity for regeneration and green plant formation. Analysis of covariance indicated that effects causing GCA for green plant formation were mainly responsible for this correlation. A regression model with two parallel lines divided the six parent lines with high green plant formation into three groups with respect to their reactions with the two testers. The results are discussed with regard to possible involvement of two sets of nuclear genes affecting the percentage of green plants obtained in wheat anther culture: one set consisting of mainly additive effects affecting green plant percentage through an initial effect on regeneration ability, and another set of two or a few more major genes with dominance or epistatic effects uncorrelated with regeneration. PMID- 24226024 TI - Flower production, male sterility and berry setting in andigena potato. AB - Unlike tuberosum, andigena potato germ plasm exhibits a high degree of genetic variation in morphological, biochemical and reproductive traits. Sixty-five percent of the 565 genotypes comprising 145 accessions of Solanum tuberosum ssp. andigena obtained from Argentina, Bolivia, Chile, Colombia and Peru remain totally vegetative and never develop any floral bud when cultivated in northern India. In 18% of genotypes, the floral buds develop but they drop off from the plants prematurely. Thus, 83% of genotypes do not develop mature flowers. The frequency of such genotypes is maximum in the Bolivian genotypes. Whereas 17% of genotypes produce mature flowers, only 2% develop berries. The highest proportion of floral bud formation and their subsequent development and differentiation into mature flowers occur in Peruvian and Colombian genotypes. Partial to high male sterility occurs in 93% of the flowering genotypes; their pollen sterility ranges from 15% to 91%. Seven percent of the flowering genotypes are completely pollen sterile. The male sterility is expressed variously, ranging from structural to sporogenous types. The floral bud formation, its development and retention to maturity, pollen and ovule functionability and fruit development are under the control of a large number of genes, most of which are unlinked and independent. Many of these genes are polygenic in nature. PMID- 24226025 TI - Meiotic behaviour of telo-tertiary compensating trisomics of rye: evaluation for use in hybrid varieties. AB - Meiosis of four telocentric-tertiary compensating trisomics of rye (Secale cereale L.) was studied with the purpose of evaluating their suitability for use in maintaining genic male-sterile lines applied in hybrid varieties. They had been constructed from four different reciprocal translocations and three different telocentrics. In one trisomic a slight, but significant tendency was demonstrated for preferential pairing of the two normal chromosomes associated with the compensating complex. This promotes the desired segregation into one normal and one compensating karyotype. In all trisomies, however, too high a frequency of failure of chiasma formation in a critical segment of the complex was evident. This is correlated with the ease of recovery of the trisomics, but results in undesired segregational products. Interstitial chiasmata leading to the formation of branched configurations were also present, more in some trisomics than in others. These also result in undesired segregations. The behaviour at meiosis was so closely correlated with the length of the chromosome segments involved that a prediction of the most favourable combination of telocentric and translocation can be made. The telocentric should be large, the corresponding translocated segment large and the interstitial segment small. The non-translocated arm of the translocated chromosome should be large and the second translocated segment small. The combinations of translocations and telocentrics had not been selected for these criteria and did not meet the requirements for practical application. PMID- 24226026 TI - Nuclear and cytoplasmic gene control of resistance to loose smut (Ustilago tritici (Pers.) Rostr.) in wheat (Triticum aestivum L.). AB - Using disomic chromosome substitution lines based on the susceptible wheat cultivar 'Chinese Spring', loose smut resistance of wheat cultivars 'Hope' and 'Thatcher' was shown to be conferred in each case by a single dominant major gene carried on chromosome 7 A ('Hope') or 7 B ('Thatcher'). Partial resistance was determined by genes on an additional eight 'Hope' or seven 'Thatcher' chromosomes, and similarities were evident between the partial resistance genotypes of'Hope' and 'Thatcher'. 'Chinese Spring' exhibited a mean infection value of approximately 50%, indicating a significant level of partial resistance, which was found to be due, in part, to genes on the homoeologous chromosome arms 1 As, 1 Es and 1 Ds, and to cytoplasmic genes. Substitution of the 'Chinese Spring' nucleus into the cytoplasm of Aegilops squarrosa, Ae. variabilis or Ae. mutica resulted in increased susceptibility to Ustilago tritici. Several alloplasmic lines of the resistant wheat cultivars 'Selkirk' and 'Chris' exhibited race-specific susceptibility to U. tritici. PMID- 24226027 TI - High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus. AB - Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 MUg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus. PMID- 24226029 TI - Urinary oxygen tension: a clinical window on the health of the renal medulla? AB - We describe the determinants of urinary oxygen tension (Po2) and the potential for use of urinary PO2 as a "physiological biomarker" of the risk of acute kidney injury (AKI) in hospital settings. We also identify knowledge gaps required for clinical translation of bedside monitoring of urinary PO2. Hypoxia in the renal medulla is a hallmark of AKI of diverse etiology. Urine in the collecting ducts would be expected to equilibrate with the tissue PO2 of the inner medulla. Accordingly, the PO2 of urine in the renal pelvis changes in response to stimuli that would be expected to alter oxygenation of the renal medulla. Oxygen exchange across the walls of the ureter and bladder will confound measurement of the PO2 of bladder urine. Nevertheless, the PO2 of bladder urine also changes in response to stimuli that would be expected to alter renal medullary oxygenation. If confounding influences can be understood, urinary bladder PO2 may provide prognostically useful information, including for prediction of AKI after cardiopulmonary bypass surgery. To translate bedside monitoring of urinary PO2 into the clinical setting, we require 1) a more detailed knowledge of the relationship between renal medullary oxygenation and the PO2 of pelvic urine under physiological and pathophysiological conditions; 2) a quantitative understanding of the impact of oxygen transport across the ureteric epithelium on urinary PO2 measured from the bladder; and 3) a simple, robust medical device that can be introduced into the bladder via a standard catheter to provide reliable and continuous measurement of urinary PO2. PMID- 24226031 TI - Screening for nodal metastasis and its challenges: nodal needles in the SCC haystack. PMID- 24226028 TI - Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats. AB - The purpose of this study was to assess whether the deleterious effect of chronic alcohol consumption differs in adult and aged female rats. To address this aim, adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% total calories) or an isocaloric isonitrogenous control diet for 20 wk. Cardiac structure and function, assessed by echocardiography, as well as myocardial protein synthesis and proteolysis did not differ in either alcohol- versus control-fed adult rats or in adult versus aged control-fed rats. In contrast, cardiac function was impaired in alcohol-fed aged rats compared with age-matched control rats. Additionally, alcohol feeding decreased cardiac protein synthesis that was associated with decreased phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle RING finger protein-1 (MuRF1). These changes were associated with increased regulated in development and DNA damage response 1 (REDD1) and phosphorylation of AMP activated protein kinase (AMPK) but no increase in AKT or forkhead transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy (e.g., LC3B, Atg7, Atg12) and TNF-alpha were increased to a greater extent in alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an enhanced sensitivity to alcohol compared with adult animals. Our data are consistent with a model whereby alcohol increases proteolysis via FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore impairs formation of a functional preinitiation complex and protein synthesis. PMID- 24226030 TI - Do metaboreceptors alter heat loss responses following dynamic exercise? AB - Metaboreceptor activation during passive heating is known to influence cutaneous vascular conductance (CVC) and sweat rate (SR). However, whether metaboreceptors modulate the suppression of heat loss following dynamic exercise remains unclear. On separate days, before and after 15 min of high-intensity treadmill running in the heat (35 degrees C), eight males underwent either 1) no isometric handgrip exercise (IHG) or ischemia (CON), 2) 1 min IHG (60% of maximum, IHG), 3) 1 min IHG followed by 2 min of ischemia (IHG+OCC), 4) 2 min of ischemia (OCC), or 5) 1 min IHG followed by 2 min of ischemia with application of lower body negative pressure (IHG+LBNP). SR (ventilated capsule), cutaneous blood flow (Laser Doppler), and mean arterial pressure (Finometer) were measured continuously before and after dynamic exercise. Following dynamic exercise, CVC was reduced with IHG exercise (P < 0.05) and remained attenuated with post-IHG ischemia during IHG+OCC relative to CON (39 +/- 2 vs. 47 +/- 6%, P < 0.05). Furthermore, the reduction in CVC was exacerbated by application of LBNP during post-IHG ischemia (35 +/- 3%, P < 0.05) relative to IHG+OCC. SR increased during IHG exercise (P < 0.05) and remained elevated during post-IHG ischemia relative to CON following dynamic exercise (0.94 +/- 0.15 vs. 0.53 +/- 0.09 mg.min(-1).cm( 2), P < 0.05). In contrast, application of LBNP during post-IHG ischemia had no effect on SR (0.93 +/- 0.09 mg.min(-1).cm(-2), P > 0.05) relative to post-IHG ischemia during IHG+OCC. We show that CVC is reduced and that SR is increased by metaboreceptor activation following dynamic exercise. In addition, we show that the metaboreflex-induced loading of the baroreceptors can influence the CVC response, but not the sweating response. PMID- 24226032 TI - The solubility of oxygen in physiological salines. AB - The oxygen solubility coefficient (alphaO2) of several different physiological saline solutions was measured over a broad range of temperatures (0 to 25?C). Distilled water had a higher value than a physiological salt solution (similar to Cortland's saline). Plasma expanders (polyvinylpyrrolidone, dextran, albumin) lowered the alphaO2 value of the physiological salt solution. A salt solution with a 4% (w/v) mixture of protein substitute had a lower alphaO2 value than the corresponding 1% mixture. The solubility of oxygen was inversely related to temperature. PMID- 24226033 TI - Elasmobranch pericardial function 2. The influence of pericardial pressure on cardiac stroke volume in horn sharks and blue sharks. AB - The importance of negative pericardial pressure to heart function in clasmobranchs has been questioned due to the discovery of positive pericardial pressures in healthy horn sharks (Heterodontus francisci). We therefore implanted electromagnetic flow probes on the ventral aorta of horn sharks and blue sharks (Prionace glauca) and assessed stroke volume and pericardial pressure as pericardial fluid volume (PFV) was varied to test the hypothesis that elasmobranchs are capable of maintaining a relatively large stroke volume at pericardial pressures near and above ambient. Stroke volume was maximum between zero and 25% maximum PFV (maximum PFV: the volume of pericardial fluid required to open the pericardioperitoneal canal), where pericardial pressure was most negative. At 50% maximum PFV (pericardial pressure near or slightly above ambient) stroke volume was 70% and 98% of its maximum in horn sharks and blue sharks, respectively. At a larger PFV, stroke volume declined drastically, reaching zero where both PFV and pericardial pressure were maximum. Thus, at a pericardial pressure apparently associated with resting or mild activity, stroke volume is a relatively large proportion of the apparent maximum. Increased circulatory demands associated with strenuous activity may induce ejection of pericardial fluid through the perieardioperitoneal canal, which then lowers pericardial pressure. The lowered pericardial pressure causes an increase in stroke volume, indicating that control is in part effected by changing pericardial pressure. PMID- 24226034 TI - Seasonal changes in reproductive condition and plasma levels of sex steroids in the blue cod,Parapercis colias (Bloch and Schneider) (Mugiloididae). AB - Gonad and plasma samples were taken from blue cod captured throughout the reproductive cycle, gonad condition was assessed, and plasma levels of 17alpha hydroxyprogesterone (17alphaOHP), 17alpha,20Beta-dihydroxy-4-pregnen-3-one (17alpha,20BetaP), testosterone (T), 17Beta-estradiol (E2) and estrone (E1) were measured by radioimmunoassay. It was confirmed that spawning occurred over an extended period in late winter and spring, with individual fish being involved in multiple spawning events. Plasma levels of T were bimodal in both sexes with peaks (maximum of 6.0 ng.ml(-1)) occurring 2 months prior to, and also during the early part of the spawning period. 17alpha,20BetaP was elevated in males (2.1 ng.ml(-1)) in mid-spermatogenesis coinciding with the first T peak (4.9 ng.m.( 1)). 17alpha,20BetaP was detectable but not significantly elevated (0.6-1.2 ng.ml(-1)) at any sample time in females. E2 was elevated in mature females (1.0 ng.ml(-1)) early in the spawning period but remained at assay detection limits (0.3 ng.ml(-1)) at all other sample times. Neither 17alphaOHP nor E1 were detectable in the plasma of either sex. It is suggested that bimodal increases in sex steroids prior to spawning may be a feature of species with rapid recrudescence. PMID- 24226035 TI - Free amino acids in metamorphosing bonefish (Albula sp.) leptocephali. AB - Metamorphosing leptocephalous larvae of the bonefish (Albula sp.) were analyzed for total ninhydrinpositive substances (NPS) and free amino acids. Total NPS content showed little change during metamorphosis. The average NPS value (+/ S.E.) for 16 larvae was 1.8 (+/-0.1) mg*larva(-1), which represents approximately 4% and 8% of the total dry weight of early and advanced larvae, respectively. Taurine was the most abundant free amino acid in whole-larva extracts, accounting for 36% and 59% of the total by weight in early and advanced larvae, respectively. The essential amino acids, leucine, isoleucine, phenylalanine, histidine, valine, methionine, lysine and arginine, accounted for about half (47%) of the total in early larvae but were reduced to about 23% of the total in advanced larvae. All of the component essential amino acids decreased during metamorphosis, but the greatest effect was seen with the first five. The remaining non-essential amino acids comprised less than 20% of the total in early larvae and, although the overall value changed little during metamorphosis, certain components such as glycine and glutamic acid showed large increases whereas others such as tyrosine and serine were reduced. Increases in amino acid content after acid hydrolysis of whole-larva extracts indicated that trichloroacetic acid-soluble, low molecular weight peptides were present in both early and advanced leptocephali. PMID- 24226036 TI - Polar and neutral lipid composition of the gonads and serum of the plaice,Pleuronectes platessa L. AB - The individual polar and neutral lipids of plaice (Pleuronectes platessa L.) ovaries, testes and serum were determined, just before spawning, in February 1984 and March 1985. Serum was also assayed in June and September 1984. Phosphatidylcholine (PC) was found to be the major polar lipid in both male and female plaice serum throughout the year and in the ovaries. The testes, however, contained almost equal amounts of PC and phosphatidylethanolamine. The polar lipid levels in plaice gonads, expressed as a percentage of the total lipid present, were higher in the ovaries than in the testes, but in male plaice serum, the percentage of polar lipid was consistently higher than in the female. In plaice testes, 86% of the total neutral lipid occurred as cholesterol, but this represented only 49% of the total neutral lipid in the ovaries, with triacylglycerol as the other major ovarian neutral lipid. PMID- 24226037 TI - Interactions among dietary minerals, arginine and lysine in rainbow trout (Salmo gairdneri). AB - Studies were conducted to determine whether interactions occur among dietary lysine, arginine and monovalent minerals in rainbow trout. In one experiment, rainbow trout fingerlings were fed diets containing three levels of lysine (2.4, 3.1 and 3.8 g per 100 g diet), two levels of arginine (1.7 and 2.5 g per 100 g diet) and two mixtures of Na(+) K(+) and Cl in a 3*2*2 factorial design. The mixtures varied in the proportions of cations to anions such that Cl equalled the sum of Na(+) and K(+) (cations - anions = 0 mEq/kg diet) in one mixture and exceeded the sum of Na(+) and K(+) (cations - anions = -200 mEq/kg diet) in the second mixture. Growth and efficiency of feed conversion were not affected by dietary lysine and arginine in fish fed diets containing - 200 mEq/kg balance, but when fish were fed diets containing a 0 mEq/kg balance, 3.8% lysine and a combination of 3.1% lysine and 2.5% arginine depressed both measures of response. Trout receiving the 0 mEq/kg cation-anion balance had significantly higher free histidine concentrations and lower free lysine concentrations in muscle and higher hepatic arginase activity (P<=0.01) than those receiving -200 mEq/kg. In another experiment, trout were fed diets containing three levels of K(+) (21, 191 and 360 mEq/kg), two levels of Na(+) (21 and 191 mEq/kg) and two levels of Cl(-) (179 and 347 mEq/kg) in a 3*2*2 factorial design. Growth and efficiency of feed conversion were depressed and hepatosomatic index increased with higher levels of dietary K(+) (P<=0.01), Na(+) (P<=0.05) and Cl (P<=0.01), with significant K(+) x Cl(+) (P<=0.01) and K(+) x Na(+) x Cl (P<=0.05) interactions. Increasing dietary K(+) resulted in increased levels of muscle free histidine and decreased levels of muscle free lysine and arginine (P<=0.01), while increasing dietary Cl increased muscle free lysine, the effect of which was dependent on dietary potassium (K(+) x Cl(-), P<=0.01). It is concluded that dietary levels of K(+), Na(+) and Cl(-), irrespective of overall cation-anion balance of these minerals, affects growth rate, efficiency of feed utilization and the metabolism of basic amino acids in tissues of trout. Excess lysine causes depressed growth and efficiency of feed utilization. These effects were due to a lysine toxicity rather than a lysine-arginine antagonism, as they were not prevented by supplemental dietary arginine. PMID- 24226038 TI - Serum metabolites related to cardiorespiratory fitness, physical activity energy expenditure, sedentary time and vigorous activity. AB - The aim of our study was to investigate the relationship between objectively measured physical activity (PA) and cardiorespiratory fitness (CRF) and serum metabolites measured by targeted metabolomics in a population- based study. A total of 100 subjects provided 2 fasting blood samples and engaged in a CRF and PA measurement at 2 visits 4 months apart. CRF was estimated from a step test, whereas physical activity energy expenditure (PAEE), time spent sedentary and time spend in vigorous activity were measured by a combined heart rate and movement sensor for a total of 8 days. Serum metabolite concentrations were determined by flow injection analysis tandem mass spectrometry (FIA-MS/MS). Linear mixed models were applied with multivariable adjustment and p-values were corrected for multiple testing. Furthermore, we explored the associations between CRF, PA and two metabolite factors that have previously been linked to risk of Type 2 diabetes. CRF was associated with two phosphatidylcholine clusters independently of all other exposures. Lysophosphatidylcholine C14:0 and methionine were significantly negatively associated with PAEE and sedentary time. CRF was positively associated with the Type 2 diabetes protective factor. Vigorous activity was positively associated with the Type 2 diabetes risk factor in the mutually adjusted model. Our results suggest that CRF and PA are associated with serum metabolites, especially CRF with phosphatidylcholines and with the Type 2 diabetes protective factor. PAEE and sedentary time were associated with methionine. The identified metabolites could be potential mediators of the protective effects of CRF and PA on chronic disease risk. PMID- 24226040 TI - Achieving balance in alert implementations. PMID- 24226041 TI - Boston strong, nursing strong. PMID- 24226042 TI - A descriptive study of point-of-care reference resource use by advanced practice RNs in Texas. AB - This descriptive study replicates and extends previous research on advanced practice RNs and the (1) reference resources available to them at the point of care, (2) resources they use to inform their clinical practice, and (3) resources they are accessing from handheld electronic devices such as PDAs, smartphones, and tablet computers during practice. These elements formed the purpose of the current study. A sample of advanced practice RNs from Texas Public Health Region 11 was surveyed. Available resources were current journals appropriate to setting and current clinical guidelines. These advanced practice RNs "always or frequently" based their professional practice on personal experience of caring for patients/clients over time, information learned in college/university, and information learned about each patient/client as an individual. Responses for Hispanic respondents as well as electronic device users were similar. Content and features accessed daily by handheld computer devices were reference materials, e mail, address/phonebook, Internet access other than e-mail, calendar/date book, alarm/reminder, calculator, and memo pad. Software installed on handheld devices and used daily included drug references, medical text/reference book, medical math/formula calculator, practice guidelines, and language translator/dictionary. Respondents who did not report using handheld devices at work were older, had more years in advanced practice nursing, and were more likely to work in a hospital, birthing center, or institution such as a prison, school, or military facility. There was no difference in resource or electronic device use by Hispanic advanced practice RNs. Electronic resources for practice are growing and being used by advanced practice RNs. Consideration should be given to incorporating evaluation and implementation of electronic clinical resources into advanced practice RN educational programs. Future research should include greater detail about the origin of information used in practice. Patient responses to the use of electronic handheld devices in clinical settings needs illuminating. PMID- 24226039 TI - Risk assessment of shellfish toxins. AB - Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the tissues of the predators, which then become toxic to animals higher up the food chain. This is a particular problem with shellfish, and many cases of poisoning are reported in shellfish consumers each year. At present, there is no practicable means of preventing uptake of the toxins by shellfish or of removing them after harvesting. Assessment of the risk posed by such toxins is therefore required in order to determine levels that are unlikely to cause adverse effects in humans and to permit the establishment of regulatory limits in shellfish for human consumption. In the present review, the basic principles of risk assessment are described, and the progress made toward robust risk assessment of seafood toxins is discussed. While good progress has been made, it is clear that further toxicological studies are required before this goal is fully achieved. PMID- 24226044 TI - Construction and validation of a distance learning module on premedication antisepsis for nursing professionals. AB - The aim of this descriptive study, carried out at a public university, was to design, develop, and validate a distance learning module on intramuscular premedication antisepsis. The content was introduced in the Modular Object Oriented Dynamic Learning Environment, based on the Systematic Model for Web Based Training projects. Ten nurses and information technologists at work consented to participate, in compliance with ethical guidelines, and answered a questionnaire to validate the Virtual Learning Environment. The educational aspects of the environment interface were mostly evaluated as "excellent," whereas the assessment of didactic resources indicated interactivity difficulties. It is concluded that distance learning is an important tool for the teaching of premedication antisepsis. To ensure its effectiveness, appropriate methods and interactive devices must be used. PMID- 24226046 TI - Editorial. PMID- 24226045 TI - Single-neuron criticality optimizes analog dendritic computation. AB - Active dendritic branchlets enable the propagation of dendritic spikes, whose computational functions remain an open question. Here we propose a concrete function to the active channels in large dendritic trees. Modelling the input output response of large active dendritic arbors subjected to complex spatio temporal inputs and exhibiting non-stereotyped dendritic spikes, we find that the dendritic arbor can undergo a continuous phase transition from a quiescent to an active state, thereby exhibiting spontaneous and self-sustained localized activity as suggested by experiments. Analogously to the critical brain hypothesis, which states that neuronal networks self-organize near criticality to take advantage of its specific properties, here we propose that neurons with large dendritic arbors optimize their capacity to distinguish incoming stimuli at the critical state. We suggest that "computation at the edge of a phase transition" is more compatible with the view that dendritic arbors perform an analog rather than a digital dendritic computation. PMID- 24226047 TI - Detection ofLegionella antibodies by enzyme-linked immunosorbent assay (ELISA) using whole cell and carbohydrate antigens. AB - The systematic study ofLegionella as a human pathogen and a bacterium widely disseminated in the environment requires simplification of present methodology. We describe a highly sensitive enzyme-linked immunosorbent assay (ELISA) for the detection of serum antibodies that can also be used for the detection of antigen.Legionella pneumophila serogroups 1 and 3 (Philadelphia 2 and Bloomington 2),L. bozemanii (WIGA), andL. micdadei (TATLOCK) were grown in diphasic medium consisting of charcoal yeast extract agar (CYE) overlayed with yeast extract medium (YEM) for the production of whole cell antigen and CYE for the extraction of carbohydrate antigen. The whole cells were inactivated with 0.5% formalin. The carbohydrate was obtained from the supernatant of cells resuspended twice in phosphate buffered saline (PBS). The antigen was sterilized and concentrated by filtration and purified by chromatography through a Sepharose 4B column. The highest molecular weight fractions were used for chemical characterization, which confirmed the carbohydrate nature of the antigen, and for micro-ELISA. Titers ranging from 5*10(3) to 3*10(5) (inverse of serum dilutions) were obtained from rabbit sera collected after 1, 2, or 3 injections of whole cells. The titers were somewhat higher and more consistent with the higher of 2 antigen concentrations used (5 or 15MUg/ml protein or dry weight), and with the carbohydrate rather than the whole cell antigen. The reactions were serogroup and species specific and only low titers were obtained with some of the heterologous antigens. The sensitivity and specificity of the reactions were not diminished when as many as 4 antigens were mixed in the same well. Thus, the micro-ELISA can be used as a test of highly specific antigens as well as a screening test with mixtures of antigens. A preliminary test withLegionella containing water specimen concentrates and high-titer rabbit sera indicated that the micro-ELISA can also be used for the detection of antigen. This investigation appears to have paved the way for the simplification of the serological methodology for the study ofLegionella. PMID- 24226048 TI - Vibrios in the Louisiana gulf coast environment. AB - A polyphasic approach, using bacteriological, immunological, and molecular biological techniques was used to elucidate the distribution of pathogenicVibrio species in the Louisiana coastal environment. A variety ofVibrio species pathogenic for man, includingV. cholerae, V. parahaemolyticus, V. fluvialis, andV. vulnificus, were found to be ubiquitous in Louisiana.Vibrio species monitored were shown to fluctuate in response to environmental factors of temperature, salinity, and nutrient level, and to vary independently of fecal coliform counts. A comprehensive serological screening system, based on species specific H antigens, was developed to identify pathogenicVibrio sp. 1 step after primary isolation.Vibrio sp. were correctly identified with accuracies ranging from 93-100%, depending on the specific H antiserum. Over 2,500V. cholerae isolates were rapidly screened for production of cholera toxin by DNA hybridization of specific toxin gene probes to colonies inoculated on nitrocellulose filter paper. The toxin gene probes, together with O antigen analysis, revealed that enterotoxigenicV. cholerae 01 serovars were recovered only from sewage stations or human disease, whereas enterotoxigenicV. cholerae non 01 serovars were recovered from environmental samples in addition to clinical and sewage samples. The results of this study indicate that techniques of immunology and molecular biology are very valuable supplements to conventional bacteriological techniques in studying the epidemiology and ecology of pathogenicVibrio sp. PMID- 24226049 TI - Survival and viability of nonculturableEscherichia coli andVibrio cholerae in the estuarine and marine environment. AB - Plating methods for estimating survival of indicator organisms, such asEscherichia coli, and water-borne pathogens includingVibrio cholerae, have severe limitations when used to estimate viable populations of these organisms in the aquatic environment. By combining the methods of immunofluorescent microscopy, acridine orange direct counting, and direct viable counting, with culture methods such as indirect enumeration by most probable number (MPN) estimation and direct plating, it was shown that bothE. coli andV. cholerae undergo a "nonrecoverable" stage of existence, but remain viable. Following 2 week incubations in saltwater (5-25%o NaCl) microcosms, total counts, measured by direct microscopic examination of fluorescent antibody and acridine orange stained cells, remained unchanged, whereas MPN estimates and plate counts exhibited rapid decline. Results of direct viable counting, a procedure permitting estimate of substrate-responsive viable cells by microscopic examination, revealed that a significant proportion of the nonculturable cells were, indeed, viable. Thus, survival of pathogens in the aquatic environment must be re-assessed. The "die-off" or "decay" concept may not be completely valid. Furthermore, the usefulness of the coliform and fecal coliform indices for evaluating water quality for public health purposes may be seriously compromised, in the light of the finding reported here. PMID- 24226050 TI - Aeromonas sobria in chlorinated drinking water supplies. AB - Aeromonas species were recovered from over 27% of 183 chlorinated drinking water samples collected during an 18-month period. Sixteen of 20 isolates tested elicited a cytotoxic response by Y-1 mouse adrenal cells. None of the strains was either enterotoxigenic by the rabbit ligated ileal loop assay, exhibited piliation, or showed significant mannose resistant adherence to human buccal cells. TheAeromonas isolates were further identified to beA. sobria and were resistant to ampicillin and susceptible to chloramphenicol, kanamycin, streptomycin, and tetracycline. Total coliform levels did not correlate withAeromonas densities in distribution water. With 85% of the samplings,Aeromonas occurred in distribution water when no coliforms were detectable by either the membrane filter or most-probable-number techniques. A significant correlation (P<.001) existed between standard plate count levels andAeromonas. PMID- 24226051 TI - Gentamicin-resistantPseudomonas aeruginosa: Concepts regarding their evolution and attenuated virulence. AB - Pseudomonas aeruginosa, a free-living bacterial species, is a major nosocomial pathogen, especially of compromised patients within medical facilities. Numerous factors contribute to the ecological selection of this bacterial species within the hospital environment, among which the expression of newly acquired or quiescent enzymatic capability seems par-amount. The emergence of pathogenic strains ofP. aeruginosa appears to be gradual, embodying a transition of strains from their natural aquatic environment, to establishing inanimate (hospital) and animate (human) reservoirs. In this stepwise transition, subsets ofP. aeruginosa may evolve which express a survival trait, for example, gentamicin resistance, but concomitantly suffer a loss of invasive potential. In this study,P. aeruginosa strains from natural [22], hospital [11], and stool [17] sources were evaluated for their physiological and exoenzymatic activity and compared with gentamicin-resistantP. aeruginosa (GRPA) strains [49] of clinical origin. As a whole, environmental and hospital isolates showed reduced enzymatic potential, for example, frequency of production of elastase, lipase, deoxyribonuclease, and pyocyanin production. Human fecal isolates most closely resembled the prototype of human invasiveP. aeruginosa in their gentamicin susceptibility (95%) and increased frequencies of exoenzymes, including elastase production. On the other hand, GRPA were frequently apyocyanogenic (9/49), lacked extracellular enzymes correlated with pathogenicity, and were rarely isolated from systemic sites. When encountered, these strains appeared to represent colonization of a body site rather than incitants of overt infection. As a "subset" ofP. aeruginosa, gentamicin resistance was seen predominantly among serotype 11 strains, and encountered most frequently from patients with localized urinary tract infections. PMID- 24226052 TI - Waterborne transmission ofCampylobacter enteritis. AB - Campylobacter jejuni is an important cause of human diarrheal disease throughout the world and likeSalmonella enteritidis, has a large animal reservoir which includes most of man's domestic animals. Until recently, it has been difficult to trace the chain of transmission from animals to man because of inadequate environmental sampling techniques and means to distinguish strains. Recent improvements in these techniques have made environmental studies more feasible in 2 water-related out-breaks.In 1 study,C. jejuni was found to be an important cause of sporadic, summertime diarrheal disease among hikers in national wilderness areas of Wyoming. In this setting, illness was significantly associated with drinking untreated surface water. SubsequentlyC. jejuni was isolated from surface water, including mountian streams, and from animals in the area. Some of the environmental isolates were serotypically identical to strains isolated from humans.A second study occurred as a result of an outbreak of Campylobacter enteritis in a community in northern Illinois which was epidemiologically associated with the community water system.Campylobacter jejuni was isolated from several surface water sources and from the implicated water system. These studies demonstrate that environmental isolation ofC. jejuni is now possible and may add to our understanding of disease transmission. PMID- 24226053 TI - The ecology of the streptococci. AB - All species of streptococci are divided into several groups according to the ecological niches they occupy. Members of the lactic acid group are found only in the plant environment and the dairy. Members of the pyogenic group and the buccal and intestinal residents of the subthermophilic group are found in intimate association only with homeothermic hosts. Members of the virulent pyogenic group, such asStreptococcus pyogenes, S. equi, andS. infrequens, are restricted to single hosts-the human, the horse, and the pig-whereas others, such asS. agalactiae can be found in several hosts. The intestinal dwellers of the subthermophilic group,S. bovis andS. equinus, occur in several animal species and are not isolated from other sources. The superficially homogeneousS. faecalis of the "enteric" group may actually consist of a group specifically restricted to the human host, and of a second group distributed among wild animals, insects, and plants. The latter group differs from the human type by the ability to hydrolyze starch and to produce a rennin-proteolytic type of curd in milk.Streptococcus faecium is widely distributed in both the homeothermic and poikilothermic environments, but no properties which differentiate the sources are known.Streptococcus faecium biot.casseliflavus has been isolated only from insects and plants.Streptococcus uberis occurs on the bovine lips and skin. Unidentified streptococci from all environments vary widely in properties. Many resembleS. lactis, S. faecalis, andS. faecium. PMID- 24226054 TI - Distribution and possible interrelationships of pathogenic and nonpathogenicAcanthamoeba from aquatic environments. AB - Among the more recently discovered agents of human disease are small, free-living amebae belonging to the generaNaegleria andAcanthamoeba. An overview of the distribution ofAcanthamoeba in recent surveys of the near shore waters of the northeastern United States is presented. There appears to be a particular association between the presence ofAcanthamoeba in marine sediments and the sites of oceanic sludge dumping. Amebae belonging to the genusNaegleria have not been isolated from these marine sediments which routinely yieldedAcanthamoeba. Starch gel electrophoretic analysis of enzymes suggests that some isolates ofAcanthamoeba from oceanic sludge dump-sites are not members of previously recognized pathogenic species. PMID- 24226055 TI - A spiroplasma of serogroup IV causes a May-disease-like disorder of honeybees in Southwestern France. AB - Honeybees affected by a disorder resembling the classical "May disease" in southwestern France contained numerous helical, motile organisms in their digestive tracts and hemolymph. Two strains of the organism (B31 and B39) were cultured and triply cloned in the BSR spiroplasma medium. The electrophoretic patterns of spiroplasmal proteins in 1 - and 2-dimensional polyacrylamide gels were similar to those of group IV spiroplasmas F1 and F2, cultured previously from flower surfaces in France. The organism could be introduced into adult bees by injection or food ingestion at various stages after emergence. Agent administered by either route multiplied to high titers in the hemolymph and killed the bees. Both multiplication and the induced lethal effect of the agent could be prevented by tetracycline but not penicillin. Spiroplasmas that were nearly identical to the B31 and B39 strains were also recovered from the surface of flowers collected within the area visited by the bees from the diseased hives. PMID- 24226056 TI - Spiroplasmas from coleopterous insects: New ecological dimensions. AB - The genusSpiroplasma (helical wall-less prokaryotes) is a recently described group of microorganisms that cause disease in plants, arthropods, and experimentally, in vertebrates. Two spiroplasmas from beetles have now been discovered in a search for microorganisms suitable for biological control of economically important coleopterous insects. Colorado potato beetles (CPB) infected with spiroplasma were commonly found on potato and other solanaceous plants in Maryland. Although this spiroplasma occurred in high concentration in gut fluids and sputum, it could not be cultivated in conventional spiroplasma media. However, another spiroplasma (CN-5 and related strains) reported here to occur commonly in association with larvae and adults of the green June beetle,Cotinus nitida, could be cultivated readily in the SM-1 formulation and several other conventional spiroplasma media. The CN-5 spiroplasma was serologically distinct from representative members of all 8 major groups now recognized. Thus, it represents a ninth major spiroplasma serogroup (IX), and can be considered to be an unnamed species. The CPB spiroplasma is apparently maintained in plant surface-insect gut cycles, but details of maintenance of the CN-5 spiroplasma are incompletely understood. Isolation of CN-5 spiroplasma from soil in which host larvae had fed suggests that transmission of this agent may occur in the soil. Both CN-5 and CPB spiroplasmas exhibited unusually active translational motility in natural fluids, and CN-5 organisms exhibited such motility in culture media. Although we have no evidence that either spiroplasma is pathogenic to its usual host, the pathogenicity of spiroplasmas to many hosts, including the beetle,Melolontha melolontha, suggests possible application for biological control. PMID- 24226057 TI - Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs. AB - RATIONALE AND OBJECTIVES: Earlier initiation of antiretroviral therapy (ART) in HIV-tuberculosis (TB) is associated with increased immune reconstitution inflammatory syndrome (IRIS). The severity, frequency, and complications of TB IRIS were evaluated in A5221, a randomized trial of earlier ART (within 2 weeks after TB treatment initiation) vs. later ART (8-12 weeks after TB treatment) in HIV-infected patients starting TB treatment. METHODS AND MEASUREMENTS: In 806 participants, TB IRIS was defined using published clinical criteria. Cases were classified as severe (hospitalization/death), moderate (corticosteroid use/invasive procedure), or mild (no hospitalization/procedures/steroids). Fisher exact, Wilcoxon, and log-rank tests were used for comparisons. MAIN RESULTS: TB IRIS occurred in 61 (7.6%) patients: 10.4% in earlier vs. 4.7% in later ART, 11.5% with CD4 <50 vs. 5.4% with CD4 >=50 cells per cubic millimeter. The CD4/ART arm interaction was significant, P = 0.014, with 44.3% of TB IRIS occurring with CD4 <50 and earlier ART. TB IRIS occurred sooner with earlier vs. later ART initiation, at a median of 29 vs. 82 days after TB treatment initiation (P < 0.001). IRIS manifestations included lymphadenopathy (59.0%), constitutional symptoms (54.1%), and radiographic changes (41.0%); central nervous system TB IRIS was uncommon (6.6%). TB IRIS was mild in 27.9%, moderate in 41.0%, and severe in 31.1%. No TB IRIS-associated deaths occurred. IRIS management required >=1 invasive procedures in 34.4%, hospitalization in 31.1%, and corticosteroids in 54.1%. CONCLUSIONS: TB IRIS was more frequent with earlier ART initiation and CD4 <50 cells per cubic millimeter. As ART is implemented earlier in HIV-TB coinfection, programs will require the diagnostic capabilities, clinical resources, and training necessary to manage TB IRIS. PMID- 24226058 TI - The VACS index predicts mortality in a young, healthy HIV population starting highly active antiretroviral therapy. AB - BACKGROUND: The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest. METHODS: NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality. RESULTS: The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%). CONCLUSIONS: The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment. PMID- 24226061 TI - Ultrastructure and development of the gametophyte vaginula-sporophyte foot complex in the liverwort Targionia hypophylla L. AB - The development of the placental complex including the gametophyte vaginula and the bulbous foot of the sporophyte in the liverwort Targionia hypophylla L. (Marchantiales) was studied by transmission electron microscopy. The vaginula and foot are separated by an intervening space and each consist of parenchymatous cells without intercellular spaces. Transfer cells begin to differentiate at the gametophyte-sporophyte interface just prior the onset of meiosis. While a single epidermal transfer-cell layer has developed in the foot by the end of meiosis, a multilayered pattern of transfer cells is formed in the vaginula. Gametophyte transfer cells have wall labyrinths which decrease in complexity with distance from the foot, lack plasmodesmata, and show signs of degeneration in the proximity of the foot. During meiosis, amyloplasts of both vaginula and foot lack starch and develop some thylakoid grana. In the subsequent stage of spore maturation, obliteration of the wall labyrinth occurs in both gametophyte and sporophyte transfer cells. The developmental pattern of the placental complex in Targionia is discussed in relation to that of mosses. PMID- 24226059 TI - Serial cervicovaginal exposures with replication-deficient SIVsm induce higher dendritic cell (pDC) and CD4+ T-cell infiltrates not associated with prevention but a more severe SIVmac251 infection of rhesus macaques. AB - OBJECTIVE: Intravaginal exposure to simian immunodeficiency virus (SIV) acutely recruits interferon-alpha (IFN-alpha) producing plasmacytoid dendritic cells (pDC) and CD4 T-lymphocyte targets to the endocervix of nonhuman primates. We tested the impact of repeated cervicovaginal exposures to noninfectious, defective SIV particles over 72 hours on a subsequent cervicovaginal challenge with replication competent SIV. METHODS: Thirty-four female Indian Rhesus macaques were given a 3-day twice-daily vaginal exposures to either SIVsmB7, a replication-deficient derivative of SIVsmH3 produced by a T lymphoblast CEMx174 cell clone (n = 16), or to CEM supernatant controls (n = 18). On the fourth day, animals were either euthanized to assess cervicovaginal immune cell infiltration or intravaginally challenged with SIVmac251. Challenged animals were tracked for plasma viral load and CD4 counts and euthanized at 42 days after infection. RESULTS: At the time of challenge, macaques exposed to SIVsmB7, had higher levels of cervical CD123 pDCs (P = 0.032) and CD4 T cells (P = 0.036) than those exposed to CEM control. Vaginal tissues showed a significant increase in CD4 T-cell infiltrates (P = 0.048) and a trend toward increased CD68 cellular infiltrates. After challenge, 12 SIVsmB7-treated macaques showed 2.5-fold greater daily rate of CD4 decline (P = 0.0408), and viral load rise (P = 0.0036) as compared with 12 control animals. CONCLUSIONS: Repeated nonproductive exposure to viral particles within a short daily time frame did not protect against infection despite pDC recruitment, resulting instead in an accelerated CD4 T-cell loss with an increased rate of viral replication. PMID- 24226062 TI - The development of the placenta in the anthocerote Phaeoceros laevis (L.) Prosk. AB - The development of the placenta in the anthocerote Phaeoceros laevis (L.) Prosk. was studied by transmission electron microscopy. By the time the sporophyte emerges from the involucre, a conspicuous placental region is formed by the intrusive growth of sporophyte foot haustorial cells into the adjacent gametophyte vaginula tissue. The separation of gametophyte cells by haustorial cells and their incorporation into the placenta are preceded by the loosening and swelling of their walls and the formation of a periplasmic space. This process causes the disruption of the plasmodesmata, and may eventually result in the complete isolation and consequent degeneration of the cells. Crystals are commonly observed in the vacuoles of gametophyte placental cells. Crystals become more abundant during cytoplasmic degeneration, and are released in the placental lacunae that result from the complete dissolution of gametophyte cells. During the subsequent phase of capsule elongation, the gametophyte placental cells that retain the symplastic connection with the adjoining gametophyte parenchyma develop a wall labyrinth typical of transfer cells. Obliteration of the wall labyrinth by deposition of lightly staining wall material is observed later in sporophyte development, in concomitance with capsule dehiscence. Crystals are negative to the periodic acid/thiocarbohydrazide/silver proteinate test for carbohydrates whilst they are completely digested by pepsin or protease, denoting protein composition. PMID- 24226060 TI - Cervicovaginal HIV-1 shedding in women taking antiretroviral therapy in Burkina Faso: a longitudinal study. AB - BACKGROUND: Antiretroviral therapy (ART) reduces transmission of HIV-1. However, genital HIV-1 can be detected in patients on ART. We analyzed factors associated with genital HIV-1 shedding among high-risk women on ART in Burkina Faso. METHODS: Plasma viral load (PVL) and enriched cervicovaginal lavage HIV-1 RNA were measured every 3-6 months for up to 8 years. Random-effects logistic and linear regression models were used to analyze associations of frequency and quantity of genital HIV-1 RNA with behavioral and biological factors, adjusting for within-woman correlation. The lower limit of detection of HIV-1 RNA in plasma and eCVL samples was 300 copies per milliliter. RESULTS: One hundred and eighty eight participants initiated ART from 2004 to 2011. PVL was detectable in 16% (171/1050) of visits, in 52% (90/174) of women. Cervicovaginal HIV-1 RNA was detectable in 16% (128/798) of visits with undetectable plasma HIV-1 RNA in 45% (77/170) of women. After adjusting for PVL, detectable cervicovaginal HIV-1 RNA was independently associated with abnormal vaginal discharge and use of nevirapine or zidovudine vs. efavirenz and stavudine, respectively; longer time on ART and hormonal contraception were not associated with increased shedding. The presence of bacterial vaginosis, herpes simplex virus-2 DNA, and the use of nevirapine vs efavirenz were independently associated with an increased quantity of cervicovaginal HIV-1 RNA. CONCLUSIONS: Certain ART regimens, abnormal vaginal discharge, bacterial vaginosis, and genital herpes simplex virus-2 are associated with HIV-1 cervicovaginal shedding or quantity in women on ART after adjusting for PVL. This may reduce the effectiveness of ART as prevention in high-risk populations. PMID- 24226063 TI - Stability and expression of transferred DNA in F1 tobacco transformants studied at various states of differentiation. AB - Grafts from the SR1 tobacco crown-gall lines NT1 (having a deletion eliminating part of the transferred (TL)-DNA auxin locus) and NT2 (having an IS60 insertion in gene 2 of this auxin locus) were cross-pollinated with pollen from nontransformed SR1 tobacco plants. One half of the resulting F1 progeny resembled the female parent ("transformed" NT1-like and NT2-like seedlings respectively) and one half resembled the male parent ("non-transformed" SR1-like seedlings). For three states of differentiation (callus, shoot, graft) all phenotypic markers of the transformed seedlings studied were identical to those of the transformed female parent. Most phenotypic markers of non-transformed seedlings corresponded with markers of the male parent. Unlike the SR1 male parent, however, the SR1 like seedlings showed the maternal traits hyperstyly and male sterility. These two traits were inherited by 100% of the F1 seedlings studied. Ninety percent of the non-transformed F2 seedlings were still male-sterile whereas in as much as 50 100% of the non-transformed F3 progeny, male fertility had been restored. The SR1 like F1 seedlings did not contain any T-DNA. At the level of restriction-fragment analysis the T-DNA structures of all 22 NT1-like seedlings examined were identical to the T-DNA structure of their female parent NT1. The steady-state level of transcripts 4 (cytokinin locus) and 6a/6b relative to transcript 3 (octopine-synthase locus) was less in shoots and grafts than in callus. Observed variation in shoot morphology among the twenty-two NT1-like seedlings was not correlated with T-DNA structure, organization and expression at the level of steady-state mRNA. The T-DNA structure of NT2 and its transformed seedlings deviated from regular border-to-border TL-DNA, in that it extended beyond the left border repeat. PMID- 24226064 TI - The Chlamydomonas cell cycle is regulated by a light/dark-responsive cell-cycle switch. AB - Cultures of the unicellular green alga Chlamydomonas reinhardii can be synchronized by light/dark cycling not only under photoautotrophic but also under mixotrophic growth conditions. We observed that cultures synchronized in the presence of acetate continue to divide synchronously for one cell-cycle period when transferred to heterotrophic growth conditions. This finding enabled us to investigate the differential effects of light on cell growth and cell division. When cells were exposed to continuous light at the beginning of the growth period they entered the division phase earlier than dark-grown cells as a consequence of an increased growth rate. Illumination at the end of the growth period, however, caused a considerable delay in cell division and an extended growth period. The light-induced delay in cell division was also observed in the presence of 3 (3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II. This finding demonstrates that cell division is directly influenced by a light/dard-responsive cell-cycle switch rather than by light/dark-dependent changes in energy metabolism. The importance of this light/dark control to the regulation of the Chlamydomonas cell cycle was investigated in comparison with other control mechanisms (size control, time control). We found that the light/dard-responsive cell-cycle switch regulates the transition from G1-to S phase. This control mechanism is effective in cells which have attained the commitment to at least one round of DNA replication and division but have not attained the maximal cell mass which initiates cell division in the light. PMID- 24226065 TI - Efficient induction by amiprophos-methyl and flow-cytometric sorting of micronuclei in Nicotiana plumbaginifolia. AB - Amiprophos-methyl (APM) is a potential herbicide which acts at the level of microtubules. By exposure of suspension cells of Nicotiana plumbaginifolia to this agent, a high degree of metaphase arrest was observed and single as well as groups of chromosomes were scattered throughout the cell, offering good prospects for application in cytology and chromosome isolation. After prolonged exposure to the drug, the chromosomes decondensed and micronuclei were formed. Based on their DNA content, the micronuclei were sorted by flow cytometry. Prospects for application of isolated micronuclei for partial genome transfer and gene mapping are discussed. PMID- 24226066 TI - Day-night changes in the levels of adenine nucleotides, phosphoenolpyruvate and inorganic pyrophosphate in leaves of plants having Crassulacean acid metabolism. AB - The levels of phosphorylated compounds studied during the dark period of Crassulacean acid metabolism (CAM) in Kalanchoe leaves showed increases for ATP and pyrophosphate and decreases for ADP, AMP and phosphenolpyruvate; levels of inorganic phosphate remained constant. Changes in adenylate levels and the correlated nocturnal increase in adenylate-energycharge were closely related to changes in malate levels. The increase in ATP levels was much inhibited in CO2 free air and stimulated after induction of CAM in short-day-treated plants of K. blossfeldiana cv. Tom Thumb. Changes in levels of phosphoenolpyruvate and pyrophosphate were independent of the presence of CO2. The results show the operation of complex regulatory mechanisms in the energy metabolism of CAM plants during nocturnal malic-acid accumulation. PMID- 24226067 TI - The relationship between turgor pressure and titratable acidity in mesophyll cells of intact leaves of a Crassulacean-acid-metabolism plant, Kalanchoe daigremontiana Hamet et Perr. AB - Day/night changes in turgor pressure (P) and titratable acidity content were investigated in the (Crassulacean-acid-metabolism (CAM) plant Kalanchoe daigremontiana. Measurements of P were made on individual mesophyll cells of intact attached leaves using the pressure-probe technique. Under conditions of high relative humidity, when transpiration rates were minimal, changes in P correlated well with changes in the level of titratable acidity. During the standard 12 h light/12 h dark cycle, maximum turgor pressure (0.15 MPa) occurred at the end of the dark period when the level of titratable acidity was highest (about 300 MUeq H(+).g(-1) fresh weight). A close relationship between P and titratable acidity was also seen in leaves exposed to perturbations of the standard light/dark cycle. (The dark period was either prolonged, or else only CO2-free air was supplied in this period). In plants deprived of irrigation for five weeks, diurnal changes in titratable acidity of the leaves were reduced (DeltaH=160 MUeq H(+).g(-1) fresh weight) and P increased from essentially zero at the end of the light period to 0.02 MPa at the end of the dark period. Following more severe water stress (experiments were made on leaves which had been detached for five weeks), P was zero throughout day and night, yet small diurnal changes in titratable acidity were still measured. These findings are discussed in relation to a hypothesis by Luttge et al. 1975 (Plant Physiol. 56,613-616) for the role of P in the regulation of acidification/de-acidification cycles of plants exhibiting CAM. PMID- 24226068 TI - Peroxidase-mediated integration of tyramine into xylem cell walls of tobacco leaves. AB - When [2-(14)C]tyramine was fed in vivo by petiolar uptake to Nicotiana tabacum Xanthi n.c. leaves partially inoculated with tobacco mosaic virus, radioactivity accumulated in inoculated areas bearing necrotic lesions, mainly in the veins and around the lesions. Light-microscopic autoradiography showed that integration of radioactivity was especially evident in xylem cell walls. This was confirmed in sections of petiole by electron-microscopic autoradiography. Study of the mechanism of insolubilisation of tyramine showed that the amine was integrated in regions in which peroxidase activity could be located cytochemically using 3,3' diaminobenzidine and H2O2 as substrates. When sections of petiole were incubated with labelled tyramine and H2O2 after fixation in glutaraldehyde, a distribution of radioactivity similar to that obtained after feeding tyramine by petiolar uptake was observed. It is concluded that simple phenols such as tyramine can be integrated in vivo into cell walls because they are oxidised by peroxidases. This result illustrates the difficulty of studying the metabolism of exogenous phenols in plants, especially in lignifying tissues which contain active wall-bound peroxidases. PMID- 24226069 TI - Gibberellin modulation of phosphatidyl-choline turnover in wheat aleurone tissue. AB - Phosphatidyl choline (PC) is synthesised in wheat (Triticum aestivum L. cv. Flanders) aleurone tissue during early germination when new endomembranes are being formed. Although gibberellic acid does not ostensibly affect PC levels, it inhibits the incorporation of choline and differentially and specifically modulates the turnover of the N-methyl and methylene carbons of the choline headgroup of PC. Gibberellic acid has no effect on turnover of the phosphate moiety of either PC or the other major phosphatides. The possible biological importance of the findings is discussed. PMID- 24226070 TI - Role of intracellular carbonic anhydrase in inorganic-carbon assimilation by Porphyridium purpureum. AB - Air-grown cells of Porphyridium purpurem contain appreciable carbonic-anhydrase activity, comparable to that in air-grown Chlamydomonas reinhardtii, but activity is repressed in CO2-grown cells. Assay of carbonic-anhydrase activity in intact cells and cell extracts shows all activity to be intracellular in Porphyridium. Measurement of inorganic-carbon-dependent photosynthetic O2 evolution shows that sodium ions increase the affinity of Porphyridium cells for HCO 3 (-) . Acetazolamide and ethoxyzolamide were potent inhibitors of carbonic anhydrase in cell extracts but at pH 5.0 both acetazolamide and ethoxyzolamide had little effect upon the concentration of inorganic carbon required for the half-maximal rate of photosynthetic O2 evolution (K0.5[CO2]). At pH 8.0, where HCO 3 (-) is the predominant species of inorganic carbon, the K0.5 (CO2) was increased from 50 MUM to 950 MUM in the presence of ethoxyzolamide. It is concluded that in air grown cells of Porphyridium. HCO 3 (-) is transported across the plasmalemma and intracellular carbonic anhydrase increases the steady-state flux of CO2 from inside the plasmalemma to ribulose-1,5-bisphosphate carboxylase-oxygenase by catalysing the interconversion of HCO 3 (-) and CO2 within the cell. PMID- 24226071 TI - Auxin-induced rapid changes in translatable mRNAs in tobacco cell suspension. AB - When 2,4-dichlorophenoxyacetic acid (2,4-D)-dependent tobacco cell suspensions, one normal and one transformed by Agrobacterium tumefaciens, were subcultured on hormone-lacking medium the stationary phase of the cell cycle was reached earlier than on medium containing 2,4-D. Addition of the auxin 2,4-D could restore cell division activity within 10-12 h for the most rapidly reacting cell line. The cell-division response was characterized as being auxin-specific and optimal with 2,4-D at 2.2 10(-6) M. Although the cell lines used showed different characteristics, both reacted with a rapid increase in at least three mRNA species within 1 or 2 h after 2,4-D application. Two, 2,4-D-induced protein spots, seen after in-vitro translation, had the same characteristics (MWs 35 kilodaltons (kDa) and 25 kDa with isoelectric points of 7.1 and 6.3, respectively) in both cell lines. Water-treated controls did not show alterations in the translatable mRNA populations. This indicates that the accumulation of the corresponding mRNAs is an early hormone-induced event. Since cell division is the only measurable reaction found after auxin application, cell systems as described here offer excellent possibilities for studying early auxin-induced changes at the molecular level preceding mitosis. PMID- 24226072 TI - Hormonal regulation of zeatin-riboside accumulation by cultured tobacco cells. AB - Auxin (11 MUM alpha-naphthaleneacetic acid) and cytokinin (1.4 MUM kinetin) regulate cytokinin accumulation by cytokinin-requiring (C(-)) and cytokinin autotrophic (C(+)) lines of Havana 425 tobacco (Nicotiana tabacum L.) tissues. No trans-zeatin riboside (ZR) (<0.5 pmol.g(-1) fresh weight) was detected in six C( ) and nine C(+) lines grown for 14 d on auxin + cytokinin and auxin medium, respectively. C(+) lines, but not C(-) lines accumulated ZR (1.9-5.1 pmol.g(-1) fresh weight) when incubated on hormone-free medium but both lines accumulated ZR when incubated on kinetin medium. Therefore, it appears that kinetin treatment can induce ZR accumulation and that this accumulation is blocked by auxin treatment. Similar effects were obtained with some lines of cells autotrophic for both auxin and cytokinin. Tobacco plants carrying the dominant Habituated leaf-1 allele (Hl-1) differ from wild-type plants in that leaf-derived tissues in culture exhibit a C(+) phenotype. No differences in ZR content were found in C(+) leaf tissues from Hl-1/Hl-1 plants and C(+) tissues that arise epigenetically in wild-type plants. This indicates that the H-1 allele does not act to induce overproduction of ZR. The Hl-1 allele is known to have oncogenic functions similar to the isopentenyl transferase (ipt) locus of the Ti plasmid. Although Hl 1/Hl-1 cells transformed with Ti plasmids defective at the ipt locus are tumorigenic and hormone-autotrophic in culture, they contain low levels of ZR typical of non-transformed Hl-1/Hl-1 cells. Therefore, the high levels of ZR characteristics of cells transformed with wild-type Ti plasmids are not necessary for expression of the tumor phenotype. PMID- 24226073 TI - Induction and floral determination in the terminal bud of Nicotiana tabacum L. cv. Maryland Mammoth, a short-day plant. AB - Floral determination in the terminal bud of the short-day plant Nicotiana tabacum cv. Maryland Mammoth has been investigated. Plants grown continuously in short days flowered after producing 31.4+/-1.6 (SD) nodes while plants grown continuously in long days did not flower and produced 172.5+/-9.5 nodes after one year. At various ages, expressed as number of leaves that were at least 1.0 cm in length above the most basal 10-cm leaf, one of three treatments was performed on plants grown from seed in short days: 1) whole plants were shifted from short days to long days, 2) the terminal bud was removed and then rooted and grown in long days, and 3) the terminal bud was removed and then rooted and grown in short days. Whole plants flowered only when shifted from short days to long days at age 15 or later. Only rooted terminal buds from plants at age 15 or older produced plants that flowered when grown in long days. Only terminal buds from plants at age 15 or older that were rooted and grown in short days produced the same number of nodes as they would have produced in their original locations while buds from younger plants produced more nodes than they would have in their original locations. Thus, determination for floral development in the terminal bud, as assayed by rooting, is simultaneous with the commitment to flowering as assayed by shifting whole plants to non-inductive conditions. PMID- 24226074 TI - Close coupling between extrusion of H(+) and uptake of K (+) by barley roots. AB - Extrusion of H(+) by intact barley (Hordeum vulgare L.) roots was automatically titrated. Simultaneously, uptake of K(+) into the roots, transport of K(+) through the roots, and (as a residual term) accumulation of K(+) within the root tissue were determined. When no monovalent cation was present in the medium the steady rate of H(+) release was close to zero. Addition of K(+) stimulated H(+) extrusion within less than 1 min. The stimulation of H(+) release was apparently limited only by the movement of K(+) through the apoplast of the roots. The steady rate of H(+) extrusion depended on the availability of external K(+) and saturated at a K(+) concentration of about 100 MUmol. dm(-3). Half-maximum rates of net K(+) uptake and H(+) extrusion were reached at a K(+) concentration of about 10 MUmol.dm(-3). With (slowly absorbable) sulfate as the only anion present, the stoichoimetry between H(+) release and net K(+) uptake was one. In conclusion, the uptake of K(+) across the plasmalemma of the cells of the root cortex is electrically coupled to H(+) extrusion. PMID- 24226075 TI - A monoclonal antibody specific for the red-absorbing form of phytochrome. AB - Characterisation of a new monoclonal antibody (mAb), designated LAS 41, directed against 124-kilodalton (kDa) etiolated-oat (Avena sativa L.) phytochrome, indicates that it recognises an epitope unique to the red-light-absorbing form, Pr. In a solid-phase enzyme-linked immunosorbent assay (ELISA), LAS 41 exhibits a seven- to eight-fold higher affinity for Pr than for the far-red-light-absorbing form of phytochrome, Pfr. In addition, in immunoprecipitation assays LAS 41 effectively precipitates 100% of phytochrome presented as Pr but only precipitates a maximum of 24.5% of phytochrome presented as Pfr. These values are indicative of binding exclusively to Pr. Peptide-mapping studies show that LAS 41 recognises and epitope located within a region 6-10 kDa from the aminoterminus of the phytochrome molecule. Since binding of LAS 41 to Pr induces alterations in the spectral properties of Pr, this indicates that at least part of the 4 kDa domain to which the antibody binds is essential for protein-chromophore interaction. Subsequent photoconversion of LAS 41-Pr complexes produces native Pfr spectra, with concomitant production of free antibody and antigen, as shown by a modified ELISA. The specificity of LAS 41 for Pr has facilitated the purification of Pfr which is free of contaminating Pr. This has enabled direct determination of the mole fraction of Pfr established by red light to be 0.874. PMID- 24226076 TI - Control of nitrate and nitrite assimilation by carbohydrate reserves, adenosine nucleotides and pyridine nucleotides in leaves of Zea mays L. under dark conditions. AB - The rate of in-vivo nitrate reduction by leaf segments of Zea mays L. was found to decline during the second hour of dark anaerobic treatment. On transfer to oxygen the capacity to reduce nitrate under dark conditions was restored. These observations led to the proposal that nitrate reductase is a regulatory enzyme with ADP acting as a negative effector. The effect of ADP on the invitro activity of nitrate reductase and the changes in the in-vivo adenylate pool under dark-N2 and dark-O2 were investigated. It was found that ADP inhibited the activity of partially purified nitrate reductase. Similarly, the in-vivo anaerobic inhibition of nitrate reduction was associated with a build-up of ADP in the leaf tissue. Under anaerobic conditions nitrite accumulated and on transfer to oxygen the accumulated nitrite was reduced. To explain this phenomenon the following hypothesis was proposed and tested. Under anaerobic conditions the supply of reducing equivalents for nitrite reduction in the plastid becomes restricted and nitrite accumulates as a consequence. On transfer to oxygen this restriction is removed and nitrite disappears. This capacity to reduce accumulated nitrite was found to be dependent on the carbohydrate status of the leaf tissue. PMID- 24226077 TI - The Pseudomonas savastanoi tryptophan-2-mono-oxygenase is biologically active in Nicotiana tabacum. AB - It has been proposed that the "eukaryotic" T-DNA-encoded indole-3-acetic acid (IAA) biosynthesis genes of Agrobacterium tumefaciens and their prokaryotic counterpart in Pseudomonas savastanoi originated from common ancestor genes. This paper provides additional evidence for the functional similarity between the gene products. We have demonstrated that a chimeric gene consisting of the coding sequence of the P. savastanoi tryptophan-2-mono-oxygenase (iaaM gene) and a plant promoter encodes an active enzyme in Nicotiana tabacum. Transformants obtained with this chimeric gene grew as a callus on hormone-free media. No stably transformed plantlets could be isolated. The callus tissues contained extremely high levels of indole-3-acetamide and slightly elevated levels of IAA. Either indole-3-acetamide by itself has a low auxin activity or, alternatively, it is converted aspecifically and at low rates into IAA. The P. savastanoi tryptophan-2 mono-oxygenase activity in plants is also able to detoxify the amino-acid analogue 5-methyltryptophan. This property can be used for positive selection of transformed calli. PMID- 24226078 TI - Vacuolar pH in radish cotyledonal mesophyll cells. AB - The vacuolar pH in cotyledonal mesophyll cells from radish (Raphanus sativus L. var. sativus) seedlings was determined from vacuoles, isolated from protoplasts through osmotic shock, by means of measurement of vacuole extracts with a pH meter and the "methylamine method", and gave mean pH values of 6.28 and 6.26, respectively. Direct in situ measurements of the vacuolar pH from intact leaf tissue were recorded with pH-sensitive microelectrodes and gave a mean value of 6.0. The results are discussed with respect to possible erroneous pH measurements and the vacuolar location of specific anabolic reactions. PMID- 24226079 TI - Quality versus quantity of social ties in experimental cooperative networks. AB - Recent studies suggest that allowing individuals to choose their partners can help to maintain cooperation in human social networks; this behaviour can supplement behavioural reciprocity, whereby humans are influenced to cooperate by peer pressure. However, it is unknown how the rate of forming and breaking social ties affects our capacity to cooperate. Here we use a series of online experiments involving 1,529 unique participants embedded in 90 experimental networks, to show that there is a 'Goldilocks' effect of network dynamism on cooperation. When the rate of change in social ties is too low, subjects choose to have many ties, even if they attach to defectors. When the rate is too high, cooperators cannot detach from defectors as much as defectors re-attach and, hence, subjects resort to behavioural reciprocity and switch their behaviour to defection. Optimal levels of cooperation are achieved at intermediate levels of change in social ties. PMID- 24226080 TI - Identification of major components of larviposition pheromone from larvae of tsetse fliesGlossina morsitans morsitans Westwood andGlossina morsitans centralis Machado. AB - The presence of pheromones produced by larvae ofGlossina morsitans morsitans andG. m. centralis, respectively, which attract gravid females and result in aggregation of pupae, is confirmed. Behavioral experiments indicated that females preferred to larviposit over moist sand conditioned by previously allowing larvae to pupariate in it. Similar results were obtained with filter papers contaminated with the prepupariation excretions of larvae and with volatiles collected from larvae prior to pupariation.n-Pentadecane andn-dodecane were identified as the dominant electrophysiologically active components of the larviposition pheromones ofG. m. morsitans andG. m. centralis, respectively, by GC-EAD and GC-MS analysis of the trapped larval volatiles. Both identified compounds were shown to significantly attract gravid females to larviposition sites in laboratory behavioral assays. PMID- 24226081 TI - Chemistry of venom alkaloids in someSolenopsis (Diplorhoptrum) species from Puerto Rico. AB - A number of 15-carbon alkaloids have been identified in venom extracts of four Puerto Rican species of ants in the genusSolenopsis (Diplorhoptrum). Workers of a species from El Verde produced thecis andtrans isomers of 2-methyl-6 nonylpiperidine with the latter isomer predominating. The same compounds were identified in queens of a species from Rio Grande, but in this species no alkaloids were detected in worker extracts. Workers of aDiplorhoptrum species collected on Mona Island produced primarily atrans-2-methyl-6-(Z-4 nonenyl)piperidine,3, with smaller amounts of thecis isomer, whereas the major compound found in the queens of the same species on Mona Island was (5Z,9Z)-3 hexyl-5-methylindolizidine, identical with the alkaloid produced by queens of a species collected on Cabo Rojo. Surprisingly, workers of the Cabo Rojo species produced (5Z,9Z)- and (5E,9E)-3-butyl-5-propylindolizidine (4 and5, respectively) reported earlier as the 223AB indolizidines from skins of dendrobatid frogs. The possible significance of the qualitative and quantitative differences in the venom alkaloids synthesized by queens and workers is discussed as is the possibility that ants containing such alkaloids may serve as a dietary source for the skin alkaloids used by certain frogs in chemical defense. PMID- 24226082 TI - Corn volatiles as attractants for northern and western corn rootworm beetles (Coleoptera: Chrysomelidae:Diabrotica spp.). AB - Synthetic corn volatiles and selected analogs were tested in commercial corn fields for attractiveness to feral northern (NCR,Diabrotica barberi) and western corn rootworm beetles (WCR,D. virgifera virgifera). Two new attractants, geranylacetone and alpha-terpineol, were identified among corn terpenes and compared at four stages in crop development with the phenylpropanoid standards cinnamyl alcohol and 4-methoxy-cinnamaldehyde, with each component at 30 mg/trap. Dose-response relationships (0.1-100 mg/trap) and efficacy of two-component blends (30 mg/component) were also examined. More beetles were captured on traps baited with (+)- than (-)-alpha-terpineol, but the difference was statistically significant only for WCR. Captures with geranylacetone or (+)-alpha-terpineol were directly proportional to the logarithm of the attractant dose. WCR females were attracted to as little as 0.1 mg of either compound. WCR males required >= 1.0 mg of (+)-alpha-terpineol and were not attracted to geranylacetone at any dose. NCR required >=0.3 mg of either attractant and showed less marked response differences between the sexes than did WCR. Geranylacetone and cinnamyl alcohol were equally effective attractants, whereas (+)-alpha-terpineol was significantly less attractive to WCR but more attractive to NCR than was 4 methoxycinnamaldehyde. Corn terpenes and phenylpropanoid standards produced similar seasonal response patterns in that captures tended to rise in each case as the season progressed, except during silking when no compound was attractive. Mixing corn terpenes or phenylpropanoid standards synergized responses of WCR females, but (+)-alpha-terpineol suppressed attraction of NCR females to geranylacetone. PMID- 24226083 TI - Control of low-density gypsy moth (Lepidoptera: Lymantriidae) populations by mating disruption with pheromone. AB - This four-year study demonstrated that low-density populations of the gypsy moth,Lymantria dispar (L.), were effectively suppressed by annual aerial application of 75 g of racemic disparlure per hectare formulated in plastic laminate flakes. These tests also showed that, when plots were treated with 150 g of pheromone per hectare in 1990 only and left untreated for the following three years, populations continued to be suppressed in 1991-1993 as compared with the controls. Although none of the plots were treated in 1994, population assessment continued and showed that the gypsy moth population density remained low in the plots that had been treated annually for the preceding four years. The laminate flakes released an average of 0.48 g disparlure per day per hectare from each of the two applications in 1990, and 0.72 g per day per hectare from the single application in each of the following three years (1991-1993). Only 27-40% of the applied pheromone dose was emitted during male moth flight. PMID- 24226084 TI - A new assay for quantifying brown algal phlorotannins and comparisons to previous methods. AB - Quantitative measurement of phlorotannins (polyphenolics) in brown algae (Phaeophyta) by colorimetric assays can be confounded because: (1) most such assays also react to nonphlorotannin substances (interferences) and (2) the appropriate reference compound for such assays is not always clear, although phloroglucinol is typically used. We developed a new assay in which 2,4 dimethoxybenzaldehyde (DMBA) reacts specifically with 1,3-and 1,3,5-substituted phenols (e.g., phlorotannins) to form a colored product. This new assay, as well as eliminating the problem of measuring interferences, is inexpensive, rapid, and can be used with small sample volumes. We recommend it for all assays of phlorotannins from one or a set of closely related species where the structural types of phlorotannins present are likely to be similar among samples. It is also appropriate for broader surveys of phlorotannin levels across many species, but in this case a reference must be chosen with care. We also compared the DMBA assay to existing assays, including the Folin-Denis [both before and after the samples were mixed with polyvinylpolypyrrolidone (PVPP)] and the Prussian blue assays. PVPP was not 100% efficient (and often much less) at removing phlorotannins from solution, and its effectiveness varied among different phlorotannins. Thus, in contrast to previous studies, measuring phenolic levels in extracts before and after treatment with PVPP will not necessarily result in an interference-free measure of phlorotannins. Based on an analysis of reactive substances in red and green algae (which do not contain phlorotannins) in the Folin-Denis and Prussian blue assays, we estimate that the average level of interferences (nonphlorotannins) in brown algae measured in these two assays is on the order of 0.5% by dry weight. PMID- 24226085 TI - Volatile compounds from crabapple (Malus spp.) cultivars differing in susceptibility to the Japanese beetle (Popillia japonica Newman). AB - The volatile compounds emitted by leaves of four crabapple cultivars susceptible to damage by Japanese beetles and four relatively resistant cultivars were examined. Twelve compounds, mostly terpene hydrocarbons, were identified from intact leaves. The terpenes (E)-beta-ocimene, caryophylene, germacrene D and (E,E)-alpha-farnesene occurred in significantly higher levels in susceptible cultivars, whereas resistant cultivars produced greater amounts of (E)-4,8 dimethyl 1,3,7-nonatriene and linalool. The relative attractiveness of the cultivars as determined in a pitfall bioassay, however, was not related to their susceptibility to the Japanese beetle as previously determined by defoliation sustained in the field. The attractiveness of individual cultivars was found to be positiviely correlated with linalool as a percent of the total volatile blend emitted by leaves. This study and previous work suggest that variation in susceptibility of crabapple cultivars to defoliation by Japanese beetles is not due to the attractiveness of the individual cultivars but rather to nonvolatile components of susceptibility and/or resistance. A scenario for host location by the Japanese beetle is presented. PMID- 24226086 TI - Volatile components in dorsal gland secretions of the collared peccary,Tayassu tajacu (Tayassuidae, mammalia). AB - Secretions of the dorsal gland of free-ranging adult male and female collared peccaries (Tayassu tajacu) were analyzed by gas chromatography-mass spectrometry. Both sexes contain (2E,6E,10E)-geranylgeraniol; squalene (allE isomer); and the following isomers of springene, a diterpene homolog of beta-farnesene: (3E,6E,10E)-alpha-springene, (3Z,6E,10E)-alpha-springene, and (6E,10E)-beta springene. A diterpene alcohol and an additional isomer each of squalene and springene also were observed. Straight- and branched-chain esters abound in the secretions of females, but they were not detected in males. PMID- 24226087 TI - Structure-activity relationship observations for the bagworm moth pheromone. AB - Structure-activity relationship (SAR) observations were made for the bagworm moth pheromone, (R)-2-pentyl decanoate, and a series of analogs with modifications in the alcohol portion of the molecule. Observed attractiveness of these analogs was related to molecular structure and their physical attributes using computational chemistry. Electrostatic potential and Van der Waals (VdW) electrostatic coded surface three-dimensional (3D) maps of the molecular mechanics (MM) minimized lowest energy conformation of the pheromone show that size, shape, charge distribution, and chirality of the molecule are related to attractiveness. PMID- 24226088 TI - Toxicity of lignans to symbiotic fungus of leaf-cutting ants. AB - Lignans fromVirola sebifera Aubl.,Virola sp., andOtoba parvifolia (Mkfg.) A. Gentry (Myristicaceae) inhibited the in vitro growth of the fungus cultivated by leaf-cutting ants of the speciesAtta sexdens rubropilosa Forel (Hymenoptera: Formicidae). A comparison of activity among the lignans was obtained. PMID- 24226089 TI - Dichloromethane attracts diabroticite larvae in a laboratory behavioral bioassay. AB - A two-choice laboratory behavioral bioassay was used to demonstrate that dichloromethane elicits the dose-dependent attraction of secondinstar western and southern corn rootworms. Preliminary data suggest that second-instar banded cucumber beetles are also attracted to dichloromethane. An eluotropic series of 10 materials, including distilled water, ethanol, methanol, acetone, ethyl dichloroacetate, dichloromethane, diethyl ether, benzene, hexadecane, and hexane, was tested for attraction of western corn rootworm larvae. Dichloromethane was the only one attractive at all doses tested, and orthogonal comparisons revealed a quadratic trend (convex) for responses of larvae to increasing dose. Benzene and hexadecane also attracted larvae, but significantly fewer than dichloromethane, and only at three doses and one dose, respectively. Orthogonal comparisons revealed no linear or quadratic trend for responses of larvae to increasing doses of either compound. Dichloromethane is the first organic compound demonstrated to attract western corn rootworm larvae in the absence of carbon dioxide. Carbon dioxide has previously been reported to attract western corn rootworm larvae either independently or when combined with other organic compounds, and the sensitivity of our bioassay was tested by demonstrating the dose-dependent attraction of western corn rootworm larvae to carbonated water as a carbon dioxide source. We have also demonstrated the attraction of southern corn rootworm larvae to carbon dioxide and propose that carbon dioxide and dichloromethane behave analogously when they interact with chemoreceptor sites on larvae. PMID- 24226090 TI - Reproductive performance and population dynamics of cowpea aphid (Homoptera: Aphididae) on leaf extracts of resistant and susceptible cowpeas. AB - Membrane feeding studies were conducted to determine the effects of raw juices and chemical extracts of leaves of aphid-resistant (ICV-12) and aphid-susceptible (ICV-1) cultivars of cowpea [Vigna unguiculata L. (Walp.)], on the survival, growth, and reproduction of cowpea aphidAphis craccivora Koch. Life table and demographic statistics of the cohort population and subsequent generations were estimated. Compared to ICV-1, the leaf juices and chemical extracts of ICV-12 exhibited significant (P<-0.05) adveres effects on aphid survival, growth, and reproduction. Raw leaf juice and ethyl acetate extract of ICV-12 in both water and sucrose significantly (P<-0.05) limited aphid performance. The adverse long term effects were often more extreme than those resulting from a diet of distilled water alone. Methanol extract of ICV-12 showed an intermediate level of adverse effects on aphids, being generally less than that of ethyl acetate but greater than that of hexane. Compared to the other ICV-12 extracts, the hexane extracts in water or sucrose media did not significantly affect the aphid performance. Overall, it was determined that antibiosis was a governing modality of aphid-resistance in ICV-12. Postingestive intoxication was caused by foliage components of seedling plants of that cultivar. PMID- 24226092 TI - Access, affordability, and insurance complexity are often worse in the United States compared to ten other countries. AB - The United States is in the midst of the most sweeping health insurance expansions and market reforms since the enactment of Medicare and Medicaid in 1965. Our 2013 survey of the general population in eleven countries-Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States-found that US adults were significantly more likely than their counterparts in other countries to forgo care because of cost, to have difficulty paying for care even when insured, and to encounter time-consuming insurance complexity. Signaling the lack of timely access to primary care, adults in the United States and Canada reported long waits to be seen in primary care and high use of hospital emergency departments, compared to other countries. Perhaps not surprisingly, US adults were the most likely to endorse major reforms: Three out of four called for fundamental change or rebuilding. As US health insurance expansions unfold, the survey offers benchmarks to assess US progress from an international perspective, plus insights from other countries' coverage-related policies. PMID- 24226091 TI - Simultaneous detection of antibodies against Apx toxins ApxI, ApxII, ApxIII, and ApxIV in pigs with known and unknown Actinobacillus pleuropneumoniae exposure using a multiplexing liquid array platform. AB - Surveillance for the presence of Actinobacillus pleuropneumoniae infection in a population plays a central role in controlling the disease. In this study, a 4 plex fluorescent microbead-based immunoassay (FMIA), developed for the simultaneous detection of IgG antibodies to repeat-in-toxin (RTX) toxins (ApxI, ApxII, ApxIII, and ApxIV) of A. pleuropneumoniae, was evaluated using (i) blood serum samples from pigs experimentally infected with each of the 15 known A. pleuropneumoniae serovars or with Actinobacillus suis, (ii) blood serum samples from pigs vaccinated with a bacterin containing A. pleuropneumoniae serovar 1, 3, 5, or 7, and (iii) blood serum samples from pigs with an unknown A. pleuropneumoniae exposure status. The results were compared to those obtained in a previous study where a dual-plate complement fixation test (CFT) and three commercially available enzyme-linked immunosorbent assays (ELISAs) were conducted on the same sample set. On samples from experimentally infected pigs, the 4-plex Apx FMIA detected specific seroconversion to Apx toxins as early as 7 days postinfection in a total of 29 pigs inoculated with 14 of the 15 A. pleuropneumoniae serovars. Seroconversion to ApxII and ApxIII was detected by FMIA in pigs inoculated with A. suis. The vaccinated pigs showed poor humoral responses against ApxI, ApxII, ApxIII, and ApxIV. In the field samples, the humoral response to ApxIV and the A. pleuropneumoniae seroprevalence increased with age. This novel FMIA (with a sensitivity of 82.7% and a specificity of 100% for the anti-ApxIV antibody) was found to be more sensitive and accurate than current tests (sensitivities, 9.5 to 56%; specificity, 100%) and is potentially an improved tool for the surveillance of disease and for monitoring vaccination compliance. PMID- 24226093 TI - Progressive cognitive decline and neuropathy in a sailor. PMID- 24226094 TI - Composite growth model applied to human oral and pharyngeal structures and identifying the contribution of growth types. AB - The growth patterns of different anatomic structures in the human body vary in terms of growth amount over time, growth rate and growth periods. The oral and pharyngeal structures, also known as vocal tract structures, are housed in the craniofacial complex where the cranium/brain follows a distinct neural growth pattern, and the face follows a distinct somatic or skeletal growth pattern. Thus, it is reasonable to expect the oral and pharyngeal structures to follow a combined or mixed growth pattern. Existing parametric growth models are limited in that they are mainly focused on modeling one particular type of growth pattern. In this paper, we propose a novel composite growth model using neural and somatic baseline curves to fit the combined growth pattern of select vocal tract structures. The method can also determine the overall percent contribution of each of the growth types. PMID- 24226096 TI - Addressing the American health-care cost crisis: role of the oncology community. AB - Health-care cost growth is unsustainable, and the current level of spending is harming our economy and our patients. This commentary describes the scope of the health-care spending problem and the particular factors in cancer care that contribute to the problem, reflecting in part presentations and discussions from an Institute of Medicine National Cancer Policy Forum Workshop held in October 2012. Presenters at the workshop identified a number of steps that the oncology community can take to reduce the rate of growth in cancer-care costs while maintaining or improving upon the quality of care. This commentary aims to highlight opportunities for the oncology community to take a leadership role in delivering affordable, high-quality cancer care. PMID- 24226095 TI - Retinoic acid-related orphan receptor alpha regulates diurnal rhythm and fasting induction of sterol 12alpha-hydroxylase in bile acid synthesis. AB - Sterol 12alpha-hydroxylase (CYP8B1) is required for cholic acid synthesis and plays a critical role in intestinal cholesterol absorption and pathogenesis of cholesterol gallstone, dyslipidemia, and diabetes. In this study we investigated the underlying mechanism of fasting induction and circadian rhythm of CYP8B1 by a cholesterol-activated nuclear receptor and core clock gene retinoic acid-related orphan receptor alpha (RORalpha). Fasting stimulated, whereas restricted-feeding reduced expression of CYP8B1 mRNA and protein. However, fasting and feeding had little effect on the diurnal rhythm of RORalpha mRNA expression, but fasting increased RORalpha protein levels by cAMP-activated protein kinase A-mediated phosphorylation and stabilization of the protein. Adenovirus-mediated gene transduction of RORalpha to mice strongly induced CYP8B1 expression, and increased liver cholesterol and 12alpha-hydroxylated bile acids in the bile acid pool and serum. A reporter assay identified a functional RORalpha response element in the CYP8B1 promoter. RORalpha recruited cAMP response element-binding protein-binding protein (CBP) to stimulate histone acetylation on the CYP8B1 gene promoter. In conclusion, RORalpha is a key regulator of diurnal rhythm and fasting induction of CYP8B1, which regulates bile acid composition and serum and liver cholesterol levels. Antagonizing RORalpha activity may be a therapeutic strategy for treating inflammatory diseases such as non-alcoholic fatty liver disease and type 2 diabetes. PMID- 24226097 TI - The imperative to address the cost of oncology care. PMID- 24226098 TI - Intermediate vaginal flora and bacterial vaginosis are associated with the same factors: findings from an exploratory analysis among female sex workers in Africa and India. AB - OBJECTIVES: Several recent studies suggest that intermediate vaginal flora (IVF) is associated with similar adverse health outcomes as bacterial vaginosis (BV). Yet, it is still unknown if IVF and BV share the same correlates. We conducted a cross-sectional and exploratory analysis of data from women screened prior to enrolment in a microbicide trial to estimate BV and IVF prevalence and examine their respective correlates. METHODS: Participants were interviewed, examined and provided blood and genital samples for the diagnosis of IVF and BV (using Nugent score) and other reproductive tract infections. Polytomous logistic regressions were used in estimating respective ORs of IVF and BV, in relation to each potential risk factor. RESULTS: Among 1367 women, BV and IVF prevalences were 47.6% (95% CI 45.0% to 50.3%) and 19.2% (95% CI 17.1% to 21.2%), respectively. Multivariate polytomous analysis of IVF and BV showed that they were generally associated with the same factors. The respective adjusted ORs were for HIV 1.98 (95% CI 1.37 to 2.86) and 1.62 (95% CI 1.20 to 2.20) (p=0.2248), for gonorrhoea 1.25 (95% CI 0.64 to 2.4) and 2.01 (95% CI 1.19 to 3.49) (p=0.0906), for trichomoniasis 3.26 (95% CI 1.71 to 6.31) and 2.39 (95% CI 1.37 to 4.33) (p=0.2630), for candidiasis 0.52 (95% CI 0.36 to 0.75) and 0.59 (95% CI 0.44 to 0.78) (p=0.5288), and for hormonal contraception 0.65 (95% CI 0.40 to 1.04) and 0.62 (95% CI 0.43 to 0.90) (p=0.8819). In addition, the association between vaginal flora abnormalities and factors such as younger age, HIV, gonorrhoea trichomoniasis and candidiasis were modified by the study site (all p for interaction <=0.05). CONCLUSIONS: IVF has almost the same correlates as BV. The relationship between some factors and vaginal flora abnormalities may be site specific. PMID- 24226099 TI - Location-based HIV behavioural surveillance among MSM in Auckland, New Zealand 2002-2011: condom use stable and more HIV testing. AB - OBJECTIVES: Over the last decade, annual HIV diagnoses among men who have sex with men (MSM) in New Zealand increased, then stabilised in 2006 and have not increased further. The aim was to examine trends in behaviours in order to better understand this pattern and inform community-based prevention. METHODS: From 2002 to 2011, we conducted five repeat cross-sectional behavioural surveillance surveys among MSM at community locations in Auckland (fair day, gay bars, sex-on site venues; n=6091). Participation was anonymous and self-completed. Recruitment methods were consistent at each round. RESULTS: Overall, the samples became more ethnically diverse and less gay community attached over time. Condom use during anal intercourse was stable across three partnering contexts (casual, current regular fuckbuddy, current regular boyfriend), with a drop among casual contacts in 2011 only. In the 6 months prior to surveys, there was a gradual decline over time in the proportion reporting >20 male partners, an increase in acquiring partners from the internet and increases in engagement in anal intercourse in some partnering contexts. HIV testing in the 12 months prior to surveys rose from 35.1% in 2002 to 50.4% in 2011, mostly from 2008. CONCLUSIONS: This first indepth examination of trends in HIV-related behaviours among five consecutive large and diverse samples of MSM in New Zealand does not suggest condom use is declining. However, subtle changes in sexual networks and partnering may be altering the epidemic determinants in this population and increasing exposure. PMID- 24226100 TI - C-reactive protein and hypertension. AB - C-reactive protein (CRP), the prototypical acute-phase reactant, is one of the most widely known biomarkers of cardiovascular disease. Circulating levels of CRP are clinically used to predict the occurrence of cardiovascular events and to aide in the selection of therapies based on more accurate risk assessment in individuals who are at intermediate risk. This paper reviews the role of CRP in hypertension. In hypertensive individuals, CRP levels associate with vascular stiffness, atherosclerosis and the development of end-organ damage and cardiovascular events. Data suggest that some anti-hypertensive medications may lower CRP levels in a manner independent of their effect on blood pressure. In individuals who are normotensive at baseline, CRP levels have been shown in multiple cohorts to foretell the development of hypertension on follow-up. Whether genetic variability that influences circulating levels of CRP independent of environmental and behavioral factors can also be used in a similar manner to predict the change in blood pressure and development of hypertension is controversial. In addition to its role as a biomarker, experimental studies have unraveled an active direct participation of CRP in the development of endothelial dysfunction, vascular stiffness and elevated blood pressure. CRP has also been implicated as a mediator of vascular remodeling in response to injury and cardiac remodeling in response to pressure overload. Emerging data may reveal novel vascular inflammatory pathways and identify new targets for treatment of vascular pathology. PMID- 24226102 TI - Bromoperoxidase activity of amavadin dissected: a DFT investigation. AB - Bromoperoxidase catalytic activity exerted by oxidated amavadin [V(HIDPA)2](-) (HIDPA = 2,2'-(hydroxyimino) dipropionate) in mono- and bis-protonated forms has been investigated by DFT. Possible reaction pathways for formation of peroxido/hydroperoxido complexes and subsequent bromide oxidation have been systematically dissected. The effect of increasing [H(+)] on catalytically active species and on halogenide oxidation has been also studied. Similarly to vanadium haloperoxidase (VHPO), the results point to a hydroperoxido amavadin adduct as the most reactive species toward bromide oxidation. However, comparison of the reactivity of amavadin and VHPO reveals also crucial differences in the catalytic mechanism of such natural V complexes. PMID- 24226103 TI - Board certification in health psychology. AB - As professional practice in health psychology has matured, mechanisms for board certification through the American Board of Professional Psychology have been developed. This article describes the American Board of Health Psychology and its role in the credentialing of practitioners who demonstrate advanced competence in the science and practice of psychology related to health, including the prevention, treatment, and rehabilitation of illness. PMID- 24226101 TI - Predictors of plasma and urinary catecholamine levels in normotensive and hypertensive men and women. AB - Age, sex, hypertension and dietary sodium are proposed to affect plasma and urinary catecholamines. Yet no prior study has examined the simultaneous effects of these factors within the same study population. So results may have been confounded by factors not determined. We investigate, for the first time, the impact of simultaneously determined predictors of plasma and urinary catecholamines and the relationship of catecholamines with the diagnosis of hypertension. Hypertensive and normotensive subjects (n=308) were studied off antihypertensives in liberal and low sodium balance. 24 h urinary catecholamines (norepinephrine and epinephrine) were measured. Plasma catecholamines were measured supine after overnight fast. Repeated measures multivariate linear regression models examined the effect of sex, race, age, body mass index (BMI), dietary salt (liberal salt vs low salt), hypertension status and mean arterial pressure (MAP) on plasma and urinary catecholamines. Logistic regression determined the relationship of catecholamines with diagnosis of hypertension. Dietary sodium restriction and increasing age predicted increased plasma and urinary norepinephrine, with sodium restriction having the greatest effect. Female sex predicted lower urinary and plasma epinephrine. Neither plasma nor urinary catecholamines predicted the diagnosis of hypertension. In summary, specific demographic factors variably impact catecholamines and should be considered when assessing catecholamines in research and clinical settings. PMID- 24226104 TI - Analysis of long-term stress reactions in emergency room patients: An initial study. AB - The psychological stress reactions of 44 family medicine patients who were treated in the emergency room were examined approximately a year after the event. Patients were assessed on several psychological measures, including one for posttraumatic stress disorder (PTSD), and on their perception of how stressful the event was initially and now. Results show continuing stress reactions related to the emergency room event. Three patients endorsed symptoms indicating full PTSD and 13 appeared to have at least partial PTSD. Age appeared to be a factor in the presence of stress symptoms and in degree of perceived communication with the physician. PMID- 24226105 TI - Multiaxial taxonomy of fibromyalgia syndrome patients. AB - Pain, disability, and depression are present in various degrees in patients with fibromyalgia syndrome. Cluster analysis was used in this research to ascertain the existence of subgroups of patients in a fibromyalgia sample based on these variables. Two clusters were defined: one characterized by high levels of pain, disability, and depression (n=51) and another characterized by low levels of pain, disability, and depression (n=67). Multivariate analysis of variance (MANOVA) confirmed differences between clusters on these health status factors and a second MANOVA revealed that the subgroup with a poorer health status reported greater passive coping, helplessness, and stress, and less satisfaction with social support, than the subgroup with better health status. Logistic regression indicated that the best discriminator of subgroup membership was helplessness. These results suggest that different approaches to patient management, particularly intervention strategies aimed at reducing helplessness, may be beneficial for patients with high levels of pain, disability, and depression. PMID- 24226106 TI - Anxious attachment and psychological distress in cardiac rehabilitation patients. AB - This study investigated the relevance of anxious attachment to the differentiation of psychologically distressed and non-psychologically distressed cardiac patients. Attachment is a biologically based behavioral system in which proximity to a special other is sought or maintained to achieve a sense of safety and security. Anxious attachment, as the name denotes, fails to achieve the function of attachment in the sense of individuals having little or no confidence in the availability of their attachment figures. Empirically, three scales (feared loss of the attachment figure, proximity seeking and separation protest) capture the features of anxious attachment as elaborated by Bowlby. These scales were administered to 178 cardiac rehabilitation patients drawn from the cardiac rehabilitation program of the Calgary General Hospital. The results indicate that feared loss and proximity seeking differentiated psychologically distressed from non-psychologically distressed patients. The implications of this finding for the understanding of psychologically distressed cardiac patients are discussed. PMID- 24226107 TI - Antihypertensive treatment, compliance, and quality of life: Review of a little understood relation. AB - If patients notoriously violate treatment regimens known to effectively control hypertension, then there must be some subjective costs associated with adherence to these regimens. Generally speaking, there must be some reduction in quality of life associated with antihypertensive medication. Unfortunately the concept of quality of life, due to its lack of specificity, is of little help in further investigating the nature of these subjective costs. We developed a simple neuropsychophysiological model based on fundamental psychological and physiological processes: corticoinhibitory effects of phasic blood pressure elevation reduce the aversive or painful qualities of many stressors. This negative reinforcement increases the rate of the reinforced physiological behavior, i.e., phasic analgesic blood pressure increases. Such negatively reinforced operant behavior is known to be extremely resistant to extinction. Counter actions such as taking antihypertensive medication not only lead to reduced quality of life due to their cancellation of the analgesic effect of conditioned blood pressure increase, but also lead to some form of reluctance to comply with treatment. The model not only provides an innovative etiological path to the emergence of neurogenic essential hypertension, but also yields a highly specific and "lean" concept of quality of life. Furthermore, it supplies the health care community with a concise explanation for the well-known low compliance of patients with their antihypertensive regimens. In addition to its parsimony, the model fits well with various experimental findings and has been operationalized and tested empirically. Specific therapeutic implications can be derived. PMID- 24226108 TI - The relationship between the Wechsler Memory Scale-Revised (WMS-R) Attention index and putative measures of Attention. AB - Although the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) is one of the more frequently used measures of memory and attention, its Attention/Concentration Index (ACI) has been minimally researched. If the ACI is to be used as a measure of "attention," the need exists to determine if it is related to other measures theoretically argued to be sensitive to attention deficits. The present study evaluated the relationship between the WMS-R ACI and other putative measures of attention by comparing individuals labeled as Attention Impaired [ACI at least 15 points < General Memory Index (GMI)] versus those labeled as Memory Impaired (GMI at least 15 points < ACI). Contrary to expectations, the Attention Impaired group scored equal to the Memory Impaired group on all measures theorized to be sensitive to attention deficits (Trails A and B time, Trails B errors, Rey AVLT interference list), except for statistically weaker performance on Trails A errors. In contrast but as expected, the Memory Impaired group scored statistically worse on all memory tests (Rey AVLT, all TPT variables). The groups also did not differ on tests argued not to be differentially affected by either attention or memory (WAIS-R FIQ, Category Test). It is concluded that the WMS-R Attention Index is not related to deficits on other measures sensitive to attention, further emphasizing the need to identify more clearly specific attention constructs. PMID- 24226109 TI - A role for clinical psychology in health care and policy concerning the physical environment. AB - Some persons adversely react to specific environments, while others are impervious or actually thrive. Medical attention often overlooks such sensitivities to the physical environment. Such sensitivities, including phobias and seasonal affectivity, fall within clinical psychology's purview. A theoretical/clinical approach called the Synchronous Systems Model, which defines and uses individual differences in people and in settings, could serve medical health care and policy. When specific people are matched appropriately with specific treatments within the most propitious settings, cost effectiveness and medical efficacy rise. Such documented accountability could make clinical psychologists central to triage of medical services as well as health care policy in these days of the shrinking health care dollar. The Synchronous Systems Model provides theory, supportive data, and clinical assessment devices to strengthen clinical psychology's role in medical settings. PMID- 24226110 TI - A chip-to-world connector with a built-in reservoir for simple small-volume sample injection. AB - We present a novel connector that allows for easy handling and injection of sample volumes between 1 and 20 MUl. All tubing connections between external pumps and the microfluidic device are established before the sample is introduced into a sealable reservoir built into the connector. This approach allows for multiple injections of small sample volumes without the need to dismantle the chip-tubing assembly. We demonstrate that the connector reservoir seal can withstand pressures of up to 6 bar, that opening or closing the reservoir does not dislocate the sample by more than 35 nl, and that the connector can be used for injecting samples into both miscible and immiscible carrier fluids. PMID- 24226111 TI - A repeated sequence probe for the C genome in Avena (Oats). AB - The genus Avena consists of at least 23 species composed of three ploidy levels. Cytogenetic analysis has characterised four distinct karyotypes. These are the A, B, C and D genomes. We have isolated a repeated sequence clone that can be used for the detection of the C genome in Avena by filter hybridization techniques. This clone, termed RS-1, is a genomic DNA clone containing at least one highly repeated sequence that is abundant in Avena species containing the C genome. This sequence or a related sequence is also present, but at much reduced levels, in species that do not contain the C genome. Because of its abundance and the characteristic Southern blot pattern, we have termed this clone a C genome specific clone. We have also done similar analysis of the Avena genus using a rDNA clone from wheat. The results of these experiments demonstrate that clearly definable C genome-specific markers can be identified with both probes. These molecular probes can be useful in studying the genomic relationships of Avena and can provide some clues as to the origin of the cultivated Avena species. These results can, therefore, provide breeders with directions for the efficient transfer of desirable traits of wild Avena species into commencal varieties. PMID- 24226112 TI - Nitrate reductases in hexaploid and tetraploid wheats and Aegilops. AB - Nitrate reductase activity (NR activity), protein content (NR protein) and polypeptides were compared in shoots of Triticum aestivum ssp. vulgare (L.) cv Fidel (bread wheat, AABBDD genome), Triticum dicoccum cv Vernal (AABB genome), Aegilops squarrosa var. strangulata (DD genome) and the amphiploid 365 (AABBDD genome), produced by crossing T. dicoccum cv Vernal and Ae. squarrosa var. strangulata. Constitutive NR protein and activity were found in shoots of all seedlings grown without nitrate, with the highest activity in the bread wheat. The inducible NR protein and activity developed upon the addition of nitrate. A 116-K polypeptide was identified as the main component of the NR from the bread wheat, while a faint, sometimes discernable 94-K band appeared on Western blots. Only one NR polypeptide could be identified in Ae. squarrosa -the 94 K. An intermediary situation was observed with the tetraploid T. dicoccum and the amphiploid: The 94-K polypeptide was the only one separated from NR of seedlings grown in the absence of nitrate. The 116-K polypeptide appeared after the addition of nitrate. The intensity of its band on the gel increased with the duration of the nitrate treatment. When comparing Ae. squarrosa and T. dicoccum, the constitutive isozyme (94-K polypeptide) was found in the D as well as in the AB genomes, while the inducible NR (116-K polypeptide) was absent from the D genome. Addition of the D genome into the AB genome slightly reinforced the expression of the inducible form (AB genome expression) in the amphiploid wheat. We postulate that the inducible form of NR in the bread wheat resulted from an evolutionary selection pressure favoured by cultivation. PMID- 24226113 TI - Inheritance of resistance in cucumber to race 2 of Colletotrichum lagenarium. AB - The resistant breeding line, AR79-95, and the susceptible cultivar, Model, were crossed to develop F1, F2, F3, and backcross populations for genetic analysis of resistance in cucumbers to race 2 of Colletotrichum lagenarium (Pass.) Ellis & Halsted., the causal agent of cucurbit anthracnose. There was no maternal effect on resistance and a small amount of F1 heterosis toward the susceptible parent. Generation means analysis showed that there was additive and dominance but no epistatic gene action detected on the scale used. Additive and dominance genetic variances were estimated, and narrow-sense heritability was low to moderate. Based on effective factor formulae, at least five effective factors contrtolled the resistance. Some of these factors were dominant and others recessive. Implications for breeding procedures are discussed. PMID- 24226114 TI - Recombination of Chlamydomonas chloroplast DNA occurs more frequently in the large inverted repeat sequence than in the single-copy regions. AB - It is well documented that chloroplast DNA (cpDNA) recombination occurs at a relatively high frequency during sexual reproduction of unicellular green algae from the Chlamydomonas genus. Like the cpDNAs of most land plants, those of Chlamydomonas species are divided into two single-copy regions by a large inverted repeat sequence, part of which encodes the chloroplast rRNA genes. In the present study, we scored the inheritance of polymorphic loci spanning the entire chloroplast genome in hybrids recovered from reciprocal interspecific and F1 crosses between Chlamydomonas eugametes and C. moewusii, and from these data, estimated the density of recombination junctions within each region of recombinant cpDNAs. Our results indicate that recombination junctions occur at highly variable frequencies across the three main domains of the chloroplast genome. The large inverted repeat sequence was found to exhibit at least a five fold higher density of recombination junctions compared to one of the singlecopy regions, whereas junctions in the latter region were five-fold more abundant relative to those in the other single-copy region. This marked difference in the densities of recombination junctions implies that the extent of genetic linkage between two given chloroplast loci will depend not only on their physical distance, but also on their locations within the genome. PMID- 24226115 TI - Extensive homologous chloroplast DNA recombination in the pt14 Nicotiana somatic hybrid. AB - In a previous study, six recombination sites have been confirmed in the chloroplast DNA (cpDNA) of pt14, a somatic hybrid of Nicotiana tabacum and Nicotiana plumbaginifolia. In the present study, physical mapping revealed six recombination sites in the 11.4-kb SalI fragment alone, only one of which has been previously identified. This fragment is located in the large unique region. We assume, therefore, that the pt14 cpDNA is a fine mosaic of the parental genomes with a recombination site about every 2 kb. A 748-bp region that comprised the intergenic region between ORF73 and ORF74B, and 460 bp of the petD intron have been sequenced. Parent-specific sequences in the pt14 DNA defined the regions within which recombination took place. The exact site of recombination events could not be determined because the parental sequences were identical between the polymorphic markers, and these sequences have been preserved in the pt14 line. PMID- 24226116 TI - Genotype, plant, bud size and media factors affecting anther culture of cauliflowers (Brassica oleracea var. botrytis). AB - Eleven F1 hybrid cultivars of cauliflower, representing a range of maturity types, were examined for their responsiveness to anther culture. Embryos were produced from each of the cultivars tested, and the mean embryo yield varied from 82.2 embryos per 100 anthers cultured for cv Dova to 0.6 embryos for cv Serrano. Variation between genotypes and between plants within a genotype was significant, both in terms of embryo yield and percentage responsive anthers. Autumn and winter maturing cauliflowers were generally more responsive than summer types. Embryo yields were enhanced by culturing anthers on solid rather than on liquid media. An increase in concentration of 2,4-Dichlorophenoxyacetic acid (2,4-D) from 0.1 to 0.3 mg/l also increased embryo yield. Embryo yield was doubled when anthers were cultured on solid media containing 0.3 mg/l 2,4-D compared to liquid media containing 0.1 mg/l 2,4-D. Although bud size alone did not have a significant effect on embryo production, genotype x bud size and plant x bud size (within genotype) interactions were significant. Estimation of the variance components demonstrated that, apart from the residual plate-to-plate variation, variation between plants was the largest source of variation, accounting for approximately 30% of total variance. Plant x bud size (within genotype) interaction accounted for 18% of total variance and genotypic differences for approximately 8%. PMID- 24226117 TI - Meiotic and isozymic characterization of plants regenerated from euploid and selfed monosomic tall fescue embryos. AB - Tissue culture of tall fescue (Festuca arundinacea Schreb., 2n=6x=42) would be enhanced by improving the callus induction and plant regeneration efficiency, and evaluating the meiotic and isozymic variation induced by culture. Mature embryos were cultured from four lines of Kenhy tall fescue and from the progeny of three selfed monosomics. Evaluation of six media-auxin combinations showed callus initiation was greatest on SH medium with 2.5 mg/l 2,4,5-T or 7.4 mg/l pCPA, while plant regeneration was greatest on SH medium with 0.5 mg/l 2,4-D. Cytological analyses of 27 plants derived from euploid parents showed a high frequency of aneuploidy (15/27). Chromosome numbers of aneuploids ranged from 36 to 41, with one plant having 80 chromosomes and two plants being asynaptic. Two of ten monosomic-derived plants were euploid, five were monosomic, one was monosomic with a fragment and two were double monosomic. Zymograms of the parents and regenerants were obtained for the enzymes ACPH, ADH, GOT, 6-PGD and PGI. Isozyme variation was observed for two groups of plants derived from the same Kenhy embryos. One group of four monosomic-derived plants differed for the enzymes GOT and ACPH, and all four plants had a PGI pattern. different from that of the parental monosomic plant. This indicated loss of a PGI allele, probably as a result of callus culture. PMID- 24226118 TI - A novel intergeneric hybrid in the Triticeae: Triticum aestivum x Psathyrost achys juncea. AB - Two hybrid embryos of intergeneric origin between Triticum aestivum cv Fukuho (2n=6x=42, AABBDD) and Psathyrostachys juncea (2n=2x=14, NN) were successfully rescued. One hybrid plant had the expected chromosome number of 28 (ABDN), whereas the second plant had 35 chromosomes. The average meiotic chromosome pairing in the 35-chromosome hybrid was 21.87 univalents + 6.38 bivalents + 0.11 trivalents + 0.009 quadrivalents, which indicates that two copies of the N genome were present. Chromosome pairing in the 28-chromosome hybrid was low (1.35 bivalents), and pointed out the lack of homology between the wheat genomes and the P. juncea genome. These new hybrids showed some necrosis and chlorosis, which caused severe floral abortion in the plant that had 35 chromosomes. These problems became gradually less severe after 18 months. PMID- 24226119 TI - High transmission of paternal plastid DNA in alfalfa plants demonstrated by restriction fragment polymorphic analysis. AB - A high frequency of paternal plastid transmission occurred in progeny from crosses among normal green alfalfa plants. Plastid transmission was analyzed by hybridization of radiolabeled alfalfa plastid DNA (cpDNA) probes to Southern blots of restriction digests of the progeny DNA. Each probe revealed a specific polymorphism differentiating the parental plastid genomes. Of 212 progeny, 34 were heteroplastidic, with their cpDNAs ranging from predominantly paternal to predominantly maternal. Regrowth of shoots from heteroplasmic plants following removal of top growth revealed the persistence of mixed plastids in a given plant. However, different shoots within a green heteroplasmic plant exhibited paternal, maternal, or mixed cpDNAs. Evidence of maternal nuclear genomic influence on the frequency of paternal plastid transmission was observed in some reciprocal crosses. A few tetraploid F1 progeny were obtained from tetraploid (2n=4x=32) Medicago sativa ssp. sativa x diploid (2n=2x=16) M. sativa ssp. falcata crosses, and resulted from unreduced gametes. Here more than the maternal genome alone apparently functioned in controlling plastid transmission. Considering all crosses, only 5 of 212 progeny cpDNAs lacked evidence of a definitive paternal plastid fragment. PMID- 24226120 TI - Extrachromosomal plasmid-like DNA in the obligate parasitic fungus Erysiphe graminis f. sp. hordei. AB - The obligate parasitic fungus, Erysiphe graminis f. sp. hordei, was found to harbour plasmid-like extrachromosomal DNA. A 1.35-kb fragment of this 9kb plasmid was cloned into the pUC12 vector. No homology was detected to nuclear or mitochondrial DNA. As only about half of the 27 isolates examined contained plasmid-like DNA, this appears to be inessential for fungal survival. The plasmid is frequent in European isolates and is found in both newly collected isolates and in isolates kept under laboratory conditions for many years. No correlation between presence of plasmid and specific avirulence/virulence genes was found. The plasmid appear to be located in the mitochondria. PMID- 24226121 TI - Implications of non-linear economic weights for breeding. AB - Relationships were studied theoretically between phenotypic values of selection candidates ('parents') and economic worth of the 'offspring' that would belong to production populations. The candidates could include individuals, crosses or clones, and the offspring could be produced either sexually or vegetatively. Cases considered included: three systems for generating production populations [clonal propagation, pair(full-sib)crosses and half-sib crosses]; three economic worth (profit) functions for individual offspring (linear, intermediate optimum, acceptable versus cull); and independently varying heritabilities for both parents and offspring. The heritabilities were varied in the model against a background of fixed genetic variance. Parental values were considered in terms of phenotypic standard deviations from the population mean, assuming normality. Lower heritabilities and, to a lesser extent, genetic segregation severely damped down the non-linearities of economic worth in relation to measured parental values, such that the linear weightings for traits in a selection index should usually be a good approximation, provided the profit function for individual offspring is monotonic. The economic advantages of corrective mating within a select population may be minimal if both heritabilities are low and the profit functions apply to individual offspring. The economic advantages accruing from genetic uniformity of clones (or crosses between inbreds) in conjunction with non linear profit functions are strongly dependent on achieving high broad-sense heritabilites, particularly in the offspring (production population). PMID- 24226122 TI - Quantitative three-dimensional study on the position of the female gametophyte and its constituent cells as a prerequisite for corn (Zea mays) transformation. AB - The position of the embryo sac in the spikelet and of the embryo sac's constituent cells within the sporophytic tissues of Zea mays was localized by scanning electron microscopy, serial thick sectioning, and computer three dimensional reconstruction. Within certain limits, the embryo sac is consistently oriented in the same position inside of the spikelet. This information is a prerequisite for successful microinjections into the in situ female cells of Zea mays. PMID- 24226123 TI - In vitro microspore reaction of different German wheat cultivars. AB - The in vitro microspore androgenesis reaction of 25 commercial German spring (including 4 Triticum durum) and 50 winter wheat cultivars was investigated. Tremendous genotypical differences were found in microspore response. The best responding winter wheat cultivai, "Florida", is characterized by the presence of a 1B/1R wheat-rye translocation chromosome. The significance of this finding and other genetic systems for future use of haploids in plant breeding is discussed. PMID- 24226124 TI - Ribosomal gene spacer length variability in cultivated and wild rice species. AB - Restriction fragment length polymorphism of the rDNA spacer was studied in the genus Oryza using a cloned rice rDNA probe. One-hundred-five accessions, including 58 cultivated rice and 47 wild species with various genome types, were analysed. Seven size classes differing from one another by an "increment" of ca. 300 bp were observed amongst the Asiatic cultivated rice of the species O. sativa. A general tendency from a smaller spacer in the Japonica subtypes to longer ones in Indica is observed. Classification as Japonica or Indica on the basis of rDNA pattern generally agrees with classification based on isozyme patterns. In contrast, African rice of the species O. glaberrima does not display any rDNA size variation. When wild species are considered, extensive variation is observed, but the fragment sizes do not fall into regularly increasing size classes except for O. rufipogon and O. longistaminata. The variation is greater in these species than in the cultivated ones. PMID- 24226125 TI - Selection system efficiencies for computer simulated progeny test field designs in loblolly pine. AB - Six simulated progeny test field designs in combination with three within-family selection systems were tested on three loblolly pine (Pinus taeda L.) progeny test sites in southeastern Oklahoma and southwestern Arkansas, to compare genetic gains for the single trait, height. Residual deviations obtained by subtraction of family and plantation mean effects for each plantation were combined with simulated genetic effects with known family variance structure. The simulated genetic populations, arranged in the following progeny test field designs - large square or almost square plots, five- and ten-tree row plots, five-tree noncontiguous plots, two tree row plots, and single-tree plots - were superimposed on the residual data for each plantation. Within-family selection methods based on deviations from block means, deviations from neighborhood means and deviations from plot means were built into the model. Realized genetic gain attained by each design - selection system combination was compared with the genetic gain theoretically possible if selection accuracy were perfect, and with expected gain estimated using the general linear model. In general, average realized genetic gain compared well with expected gain. Differences between designs with large versus small plots were generally lower than expected, although the single-tree plot design always yielded highest realized gain. Realized gain was generally higher than expected when within-family selection was based on deviations from block or neighborhood means, but equal to or lower than expected when selection was based on deviations from plot means. PMID- 24226126 TI - Modifications of floral development in tobacco induced by fusion of protoplasts of different male-sterile cultivars. AB - Protoplasts derived from different cytoplasmic male-sterile cultivars of Nicotiana tabacum were fused. Nearly 200 cybrid calli were regenerated into plants and their flower morphologies were examined. Most cybrids exhibited parental-type male-sterile morphologies. Some, however, showed novel male-sterile phenotypes or phenotypes which combined traits of both male-sterile parents in a new combination. Others were restored to fertility, with stamens which produced functional pollen. PMID- 24226127 TI - Genetic and environmental factors in the resistance of Drosophila subobscura adults to high temperature shock : 1. Breeding temperature and crowding. AB - Survival time following a high temperature shock of Drosophila subobscura adults in dry air has shown great variability. This experimental condition involved desiccation as the first cause of death. Here survival is studied under saturation humidity, so that the mortality may be imputed only to thermic stress. We analyze the influence of culture temperature and crowding on resistance for different sex and age of the adults. The results show strong influences of these environmental factors on heat shock resistance and show interactions with the age and sex of the adults. We suggest that these facts could be due to acclimatization and/or to adaptation. The acclimatization would occur during development and would affect physiological processes related to aging of the flies. The adaptation would take place for selection, acting through differential mortality before the heat shock. Of course, other processes could be significant. Whatever the causal explanation, it will be necessary in any future research related with heat shock resistance to take these factors into account. PMID- 24226128 TI - The effects of 'gibberellin-insensitive' dwarfing alleles in wheat on grain weight and protein content. AB - Three series of near-isogenic wheat lines differing in dwarfing alleles, in the varietal backgrounds of 'Maris Huntsman', 'Maris Widgeon' and 'Bersee', and the F2 grain on intravarietal F1 hybrids, produced with a chemical hybridising agent, were examined for grain size and protein content. Individual F2 grains from Rht1/rht, Rht2/rht and Rht3/rht F1 spikes were classified for Rht genotype by assaying embryo half grains in a gibberellic acid seedling response test, while the remaining half was used for protein determination. Mean grain weight and protein percentage were lower in all homozygous isogenic lines and the Rht/rht F1 hybrids than in the respective tall lines, in an allele dose-dependent manner. In all the hybrids, the Rht genotype of individual F2 grains, which segregated within the spikes of F1 plants, had no significant effects on grain weight or protein. Consequently, the pleiotropic effects of the Rht alleles on these yield and quality components must be attributed to their presence in maternal plant tissues rather than in the endosperm or embryo tissues of individual grains. PMID- 24226129 TI - Introgression of Allium fistulosum L. into Allium cepa L.: cytogenetic evidence. AB - A diploid Allium cepa plant was recovered from the backcross of an interspecific triploid (2 x A. cepa + 1 x A. fistulosum) to an A. cepa diploid which exhibited both A. cepa and A. fistulosum Adh-1 alleles. Cytogenetic analyses revealed a recombinant sub-telocentric chromosome. The ADH-1 locus is believed to be on the long arm of the sub-telocentric A. fistulosum chromosome 5. Meiosis of the triploid progenitor gives strong evidence that recombination occurred. A. fistulosum chromosome 8 has been substituted for A. cepa chromosome 1. PMID- 24226130 TI - Chloroplast DNA in Pinus monticola : 1. Physical map. AB - Restriction sites on the chloroplast genome of Pinus monticola have been mapped, and the gene for the large subunit of ribulose bisphosphate carboxylase/oxygenase, the genes for the photosystem II polypeptides psbA, psbD and psbC, and the 16S and 23S ribosomal RNA genes have been located. The genome lacks the large inverted repeat characteristic of most angiosperms. The gene order is similar to that found in P. radiata. The presence of dispersed repeated sequences is likely. Two structural features, lack of a large inverted repeat and the presence of dispersed repeats, may confer a degree of variability on the genome which will prove useful in studies of population structure. PMID- 24226131 TI - The genetic interaction between non-nodulation and supernodulation in soybean: an example of developmental epistasis. AB - The interaction between three non-nodulation mutants (nod49, nod772 and nod139) and a supernodulation mutant (nts382) of soybean was studied by analysing the progeny from crosses between these mutants. Previously it had been shown that the non-nodulation mutants arose from single mutation events and that nod49 and nod772 are allelic, whereas nod139 represents another gene required for nodulation. Analysis of progeny from crosses between nts382 and the wild type showed that this mutant also arose from a single mutation. Complementation tests demonstrated that the mutation responsible for supernodulation in nts382 is not allelic to either of these non-nodulation characters, and that it segregates independently. Progeny were identified that were homozygous for both supernodulation and non-nodulation, and these plants were incapable of nodulation. Thus, non-nodulation is epistatic over supernodulation and this is discussed in terms of the developmental blockage in the two mutant types. The identification and confirmation of these double mutants of the supernodulation and non-nodulation mutations are described. Although the non-nodulation mutations behave as recessive characters in a wild-type background, these mutations are incompletely dominant in a genetic background homozygous for supernodulation. The significance of these results to the understanding of nodule ontogeny is discussed. PMID- 24226132 TI - Energy expenditure and locomotor activity in mice selected for food intake adjusted for body weight. AB - The aim of this study was to examine the differences in physical activity and their contribution to differences in energy utilization in mice, selected either high or low for food intake, adjusted for body weight, which show correlated responses in lean content and metabolic rate. Simultaneous measurements of fasting metabolic rate and activity were made in lines of mice selected at either: a young age, 4-to 6-week food intake corrected for 4-week body weight; or an older age, 8- to 10-week food intake corrected for mean weight at 8 and 10 weeks of age. Correlated response in metabolic rate was found to have been accompanied by changes in locomotor activity near the ages at selection in both sets of lines. Activity, however, accounted for only a small proportion of variation in fasting heat production, generally less than 5%, although a highly positive correlation (r=0.63) between the two traits was found. It was concluded that selection for food intake adjusted for body weight has led to correlated response in physical activity. In consequence, mice selected in the upward direction expend some of the excess energy intake rather than assimilating it as body mass and are, therefore, slightly leaner than their counterparts selected in the downward direction. PMID- 24226133 TI - Cytology of F1 hybrids and chromosome number of F2 and BC 1 progeny of the cross Bromus riparius x B. inermis. AB - Hybrids between B. inermis Leyss (2n=8x=56) and B. riparius Rehm. (2n=10x=70) were easily made. The F1 hybrids had a fertility of 20%-50% under open pollination and backcrossing to B. inermis. Chromosome pairing in B. riparius was predominantly as bivalents (29.04-33.85 per cell for plant means). Bivalents also predominated in the F1 hybrid (2n=9x=63) and there was a high level of pairing with no reduction in chiasma frequency. It was impossible to estimate the frequency of auto-versus allosyndetic pairing. Chromosome pairing in a hybrid between B. arvensis (2n=2x=14) and B. riparius confirmed that the B. riparius complement is capable of complete autosyndetic pairing. Chromosome numbers in the F2 progeny ranged from 2n=56 to 72 but they were skewed towards 2n=63 to 70. Backcrosses ranged from 2n=56 to 63, as expected, with the distribution skewed towards 2n=56. Selection towards the 2n=56 level would be difficult in the F2. Empirical observation suggested that cytoplasm had a major influence on morphology in the backcrosses. Additional studies are required to determine the best breeding scheme to introgress germ plasm between B. inermis and B. riparius. PMID- 24226134 TI - Aerosol matrix-assisted laser desorption ionization mass spectrometry. AB - A new method of liquid sample introduction for a time-of-flight mass spectrometer (TOF-MS) has been developed by applying the method of matrix-assisted laser desorption ionization to aerosols. Analyte biomolecules are dissolved in a methanol solvent along with a UVabsorbing matrix and formed into an aerosol with a pneumatic nebulizer. The aerosol particles are dried in a heated skimmer tube before ionization by pulsed 355-nm UV laser radiation. Mass analysis is achieved in a linear TOF-MS. Results for the ionization of bovine insulin (5733.5 Mw) are reported. PMID- 24226135 TI - Matrix-assisted laser desorption mass spectrometry of biotransformation products of dynorphin a in vitro. AB - The utility of matrix-assisted laser desorption mass spectrometry for characterizing products of in vitro processing of synthetic dynorphin A (Dyn A) peptides in biologic matrices is described. A series of laser desorption matrices were tested for their response to Dyn A (1-6), Dyn A (1-7), Dyn A (1-8), Dyn A (1 9), Dyn A (1-l0), Dyn A (1-13), Dyn A (2-17), and Dyn A (1-17). alpha-Cyano-4 hydroxycinnamic acid was chosen as a suitable matrix for subsequent studies. Mass spectra of dynorphin peptides indicated a good signal-to-noise response down to (1) 10 fmole of Dyn A (1-10) amide standard in aqueous acidic solution and (2) a concentration of 10(-7) M for seven dynorphin peptides spiked into human plasma. Two examples of the mass spectrometric analysis of the products of in vitro processing are presented: Dyn A (1-13) and Dyn A (1-17) in human blood. The presence and identity of processed peptides can be simply inferred from the molecular masses provided by the mass spectrometric measurement without extensive sample purification. A comparison of matrixassisted laser desorption mass spectrometry is made with high-performance liquid chromatography. PMID- 24226136 TI - An aerodynamic drag model for protein ions. AB - The energy losses of protein ions passing through a collision cell filled with inert gas have been modeled as the aerodynamic drag on a projectile at high Knudsen number. When applied to the energy loss data of Covey and Douglas (J. Am. Soc. Mass Spectrom. 1993, 4, 616-623) with drag coefficients from the gas dynamics literature, derived protein cross sections are ~0.8 of those found with the simple collision model used by Covey and Douglas. PMID- 24226137 TI - Probing high order structure of proteins by fast-atom bombardment mass spectrometry. AB - During the past decade, numerous investigations have demonstrated that the rate at which amide hydrogens located at peptide linkages undergo isotopic exchange is a sensitive probe of the high order structure and dynamics of proteins. The present investigation demonstrates that microbore high-performance liquid chromatography (HPLC) continuous-flow fast-atom bombardment mass spectrometry (FABMS) can be used to accurately quantify deuterium located at peptide linkages in short segments of large proteins. This result is important because it demonstrates the feasibility of using mass spectrometry as a tool for studying the high order structure and dynamics of large proteins. Following a period of deuterium exchange-in, a protein was placed into slow-exchange conditions and fragmented into peptides with pepsin. The digest was analyzed by continuous-flow HPLC FABMS to determine the molecular weights of the peptides, from which the number of deuterons located at the peptide linkages could be deduced. The HPLC step was used both to fractionate the peptides according to their hydrophobicities and to remove through back-exchange all deuterium except that located at peptide amide linkages. This approach has been applied to alpha crystallin, a lens protein composed of two gene products with monomer molecular weights of 20 kDa and an aggregate molecular weight approaching 1000 kDa. Results from this study show that some of the peptide amide hydrogens in alphaA crystallin exchange very rapidly (k > 10 h(-1)) while others exchange very slowly (k < 10(-3) h(-1)). The ability not only to detect that a conformational change has occurred, but also to identify the specific regions within the protein where the change occurred, was demonstrated by measuring changes in the exchange rates within these regions as the deuterium exchange-in temperature was increased from 10 to 80 degrees C. PMID- 24226138 TI - Determination of ion frequencies in a quadrupole ion trap by using a fast direct current pulse as pump and a laser probe. AB - A new technique has been developed which allows the direct measurement of frequencies of ions trapped in a quadrupole ion trap mass spectrometer. This pump/probe method employs a fast direct current (DC) pulse (pump) to displace a kinetically cooled ion population from the center of the trap, and a laser (probe) which recognizes when ions reappear at the center of the trap by the formation of photodissociation fragments. The translationally excited ions undergo periodic motion within the confines of the ion trap, and this periodic motion can be followed by recording the intensity of the photodissociation fragment as a function of the delay time between the DC pump and the laser probe. The DC pulse has a rise time of 15 ns; data are taken 1 ms after its application to allow stable ion motion to be sampled. Sampling of the ion cloud is done at 50 ns intervals, and fast Fourier transformation of the time-based data yields the ion frequencies and their relative magnitudes. Data are reported for ions derived from acetophenone (m/z 105) and 1,4-cyclohexadiene (m/z 80) under various trapping conditions corresponding to different Mathieu qz values. The measured fundamental secular frequencies, fz and fr, are found to agree well with those predicted. The presence of higher order multipole contributions to the trapping field is evident from such ion frequencies as the drive frequency, fRF,. The ability to measure ion frequencies under operating conditions provides a new tool for comparing simulated and experimental data. Simulation data from the program ITSIM, modified to account for the effects of collisions, are shown to predict the major frequency components observed in the experimental data. PMID- 24226139 TI - Charge compensation for imaging large insulating samples by using secondary ion tandem mass spectrometry. AB - A charge compensation technique has been developed for secondary ion mass spectrometry and imaging of insulating samples as large as 1 cm(2) using a triple quadrupole-based microprobe. The microprobe secondary ion extraction field is synchronized with a periodic primary Cs(+) beam to allow a sheetlike beam of 5-eV electrons to pass over the sample surface when the extraction field is zeroed. Electrons are attracted to, and neutralize, any points on the sample that have accumulated positive charge. Positive secondary ion images from Teflon(r), a well known insulator, illustrate the effectiveness of charge compensation. Locating and identifying analytes on dry filter paper by using tandem mass spectrometry are also demonstrated. PMID- 24226140 TI - Correlation between electron capture negative chemical ionization mass spectrometric fragmentation and calculated internal energies for polychlorinated biphenyls. AB - Correlationbse tween molecular structure and fragmentation observed in electron capture negative chemical ionization mass spectra (moderator gas = methane) of 49 selected tetrachlorinated, pentachlorinated, and hexachlorinated biphenyls have been investigated by using molecular modeling. The semiempirical general molecular orbital program MOPAC was used to calculate molecular properties for biphenyl and the 209 polychlorinated biphenyls. The mass spectrometric ionization and fragmentation processes were found to be linked to the number of chlorine atoms present on the biphenyl, and to the number of those chlorine atoms in the ortho (2, 2', 6, and 6') positions. The intensity of molecular ions increased with the number of chlorine atoms present, but this was counteracted by enhanced fragmentation as the number of ortho position chlorine atoms increased. The molecular parameters that were most closely linked with the number of ortho chlorine atoms were the twist angle between the phenyl rings and the energy of the lowest unoccupied molecular orbital (LUMO). It is suggested that fragmentation occurs when the energy of the ionizing electron exceeds the energy difference between the LUMO and LlJMO + 1 orbitals. PMID- 24226143 TI - Health and physical function predicting strength and balance training adoption: a community-based study among individuals aged 75 and older. AB - This study was conducted to determine the characteristics of health and physical function that are associated with not starting strength and balance training (SBT). The study population consisted of 339 community-dwelling individuals (75 98 years, 72% female). As part of a population-based intervention study they received comprehensive geriatric assessment, physical activity counseling, and had the opportunity to take part in SBT at the gym once a week. Compared with the SBT-adopters, the nonadopters (n = 157, 46%) were older and less physically active, had more comorbidities and lower cognitive abilities, more often had sedative load of drugs or were at the risk of malnutrition, had lower grip strength and more instrumental activities of daily living (IADL) difficulties, and displayed weaker performance in Berg Balance Scale and Timed Up and Go assessments. In multivariate models, higher age, impaired cognition, and lower grip strength were independently associated with nonadoption. In the future, more individually-tailored interventions are needed to overcome the factors that prevent exercise initiation. PMID- 24226144 TI - Secretion of hatching enzyme and its proteolytic activity in coregoninae (Coregonus albula L andC. lavaretus L) embryos. AB - After the electrial stimulation Coregoninae embryos secreted the hatching enzyme (chorionase) within 0.1-0.5 h, and the dissolution of their chorions lasted 1.2 2.0 h, depending on embryo's developmental stage (DS 13 or DS 14) and water temperature (5.2 or 9.6-9.8 degrees C).Crude chorionase (hatching liquid) ofCoregonus albula andC. lavaretus was collected in large quantities by means of the electric stimulation of eggs. In both species the temperature optimum of proteolytic activity of the crude chorionasc was 30 degrees C; the activity was lost at temperatures < 3-2 degrees C and > 35-40 degrees C. The maximal proteolytic activity was observed at pH 8.5; a rapid decrease in enzyme activity was evident at pH < 7.0, and the activity was zero at pH 6.The temperature activity curve of chorionase may reflect the adaptation of Coregoninae to hatching immediately after the ice cover recedes from lakes, whereas the rapid decrease of enzyme activity at pH 7 -pH 6 can affect adversely the process of hatching in acidified lakes. PMID- 24226145 TI - Oxygen consumption and responses to hypoxia of ammocoetes of the southern hemisphere lampreyGeotria australis. AB - The standard rate of oxygen consumption of ammocoetes (larvae) ofGeotria australis with a mean weight of c. 0.5 g was 9.6, 31.4 and 59.4MUl g(-1) h(-1) at 4.5, 15.5 and 25.0 degrees C respectively, which gives an overall Q10 of 2.4. The regression coefficient for the logarithmic relationship between oxygen consumption and body weight at 15.5 degrees C was 0.704. The ammocoetes ofG. australis have a much lower rate of oxygen consumption at 15.5 and 25.0 degrees C than those of holarctic lampreys. This presumably reflects the lower oxygen delivery pressure to their tissues and helps account for their slow growth rate. At 15.5 degrees C, ammocoetes ofG. australis emerged from the substrate at 21-25 mm Hg and, unlike those of the Northern HemisphereIchthyomyzon greeleyi, died at 14-17 mm Hg. Thus, despite having a thinner water/blood barrier in the gills and blood with a higher oxygen affinity and capacity than holarctic ammocoetes, the larvae ofG. australis cannot survive very low dissolved oxygen tensions. This is apparently related to an inability of larvalG. australis to meet the high oxygen requirements of the respiratory pump at these oxygen tensions. During metamorphosis, oxygen consumption at 15.5 degrees C rose from approximately 27MUl g(-1) h(-1) at the beginning of transformation to 33.2MUl g(-1) h(-1) by Stage 3 and then rapidly to 66MUl g(-1) h(-1) at Stage 6. It remained near this level in Stage 7 and the downstream migrant. PMID- 24226146 TI - An analysis of the energetic cost of the branchial and cardiac pumps during sustained swimming in trout. AB - Experimental data are available for the oxygen cost of the branchial and cardiac pumps in fish. These data were used to theoretically analyze the relative oxygen cost of these pumps during rest and swimming in rainbow troutSalmo gairdneri. Efficiency of the heart increases with activity and so the relative oxygen cost of the cardiac pumps decreased from 4.6% at rest to 1.9% at the critical swimming speed. The relative oxygen cost of the branchial pump is significant in the resting and slowly swimming fish, being 10 to 15% of total oxygen uptake. However, when swimming trout switch to a ram mode of ventilation, a considerable saving in oxygen cost is accrued by switching the cost of ventilation from the branchial to the tail musculature. Thus, the relative oxygen cost of the branchial and cardiac pumps actually decreases at critical swimming speed compared to rest and therefore is unlikely to be a major limiting factor in maximum oxygen delivery to the tissues. PMID- 24226147 TI - Autocatalytic pathways to cell death: A new analysis of the tuna burn problem. AB - During capture and storage of tuna, a small but significant number of fish display a characteristic muscle degeneration termed tuna burn. Based on detailed amino acid analyses and on previous studies of metabolite changes during online swimming of tuna, a new model of the etiology of burnt muscle is developed. According to this model oxygen-lack to white muscle (developing initially during capture) leads to a metabolic collapse, to a drop in ATP concentration, to a consequent opening of ATP-dependent K(+) channels, with an efflux of K(+), and thus to a collapse of membrane potential. When the membrane potential falls far enough to open voltage-dependent Ca(++) channels, Ca(++) influx occurs leading to elevated Ca(++) concentrations in the cytosol. This process is augmented by simultaneous movement of Ca(++) from sarcoplasmic reticulum (SR) and from mitochondria into the cytosol. At high intracellular concentrations Ca(++) can be devastating. One of its more notable effects involves the activation of Ca(++) dependent proteases, which preferentially target key components of the contractile machinery (troponins, tropomyosin, C-protein, M-protein, Z-discs, alpha-actinin) and thus cause disassembly of myofilaments prior to any significant hydrolysis of myosin or actin. This process is autocatalytic in the sense that Ca(++)-activated proteases may act upon SR, thus increasing Na(+) /Ca(++) exchange, and ultimately adding more Ca(++) to the cytosolic pool. According to this model, the difference between burnt and unburnt regions of the myotome is simply due to how far each region has moved along this self destructive, autocatalytic pathway. The model is helpful in explaining previously perplexing data and in making useful (i.e. measurable) predictions for further studies of this important problem. PMID- 24226148 TI - Renal corpuscle development in boreal fishes with and without antifreezes. AB - Light and election microscopy were used to document the degree of renal corpuscle development in boreal telcost fishes that produce peptide or glycopeptide antifreeze compounds on a seasonal or permanent basis. Emphasis was placed on gadids, cottids and pleuronectids from both the North Atlantic and North Pacific Oceans. Based on the classification of Marshall and Smith (1930), corpuscle development ranged from fully glomerular (Type 1) to pauciglomerular (Type III). Unlike the situation in Antarctic notothenioid fishes, there were no aglomerular species among the boreal fishes. Corpuscles were small in diameter in gadids whereas in cottids they ranged from small to large with considerable intraspecific variation. Eight of eleven species with antifreeze had intermediate (Type II-III) or pauciglomerular kidneys with relatively few dense corpuscles (dia. 36-82MUm). In some of these species an extensive mesangium and a substantial capillary endothelium contributed to a glomerular filtration barrier that was four to five times thicker than that in Type I kidneys. The corpuscles of other pauciglomerular species were unremarkable and appeared functional at the ultrastructural level. The boreal fish fauna is taxonomically diverse and, compared to the unrelated Antarctic fauna, of relatively recent evolutionary origin. Furthermore, antifreeze is present only during the winter in some species. Hence it is not surprising that the urinary conservation of antifreeze is accomplished by mechanisms other than the evolutionary loss of renal corpuscles. PMID- 24226149 TI - Osmoregulatory ability of chum salmon,Oncorhynchus keta, reared in fresh water for prolonged periods. AB - The osmoregulatory ability of chum salmon (Oncorhynchus keta), reared in fresh water for a prolonged period, was examined by transferring them directly to seawater and then back to fresh water. When fry and juveniles weighing 0.3-125g, reared in fresh water for 1.5-13 months, were transferred directly to seawater, they adjusted their plasma Na(+) concentration to the seawater-adapted level within 12-24h. When they were transferred back to fresh water after having been adapted to seawater for 2 weeks, the plasma Na(+) level gradually decreased during the first 12-24h, and then increased to reattain the initial freshwater level after 5-7 days. No mortality was observed during the experiment except among the smallest fry weighing about 0.3g after transfer to seawater (2.1%). The maintenance of good osmoregulatory ability of the chum salmon for a prolonged period in fresh water seems to be unique among Pacific salmon, with the possible exception of the pink salmon.Changes in plasma levels of hormones during the transfer experiments were recorded in juveniles reared in fresh water for 13 months. Prolactin levels increased maximally 3 days after transfer from seawater to fresh water, as would be expected from its well-established role in freshwater adaptation in several euryhaline teleosts. In addition, an increase in plasma growth hormone was observed during the first 12h after seawater transfer, along with a tendency towards a decrease during freshwater transfer, suggesting an important role for this hormone in seawater adaptation. There were no consistent changes in plasma levels of thyroxine and cortisol during freshwater to seawater or seawater to freshwater transfer. PMID- 24226150 TI - First international symposium on fish endocrinology. PMID- 24226151 TI - Clinical and immunological factors associated with bullous pemphigoid relapse. PMID- 24226153 TI - Flexible high-repetition-rate ultrafast fiber laser. AB - High-repetition-rate pulses have widespread applications in the fields of fiber communications, frequency comb, and optical sensing. Here, we have demonstrated high-repetition-rate ultrashort pulses in an all-fiber laser by exploiting an intracavity Mach-Zehnder interferometer (MZI) as a comb filter. The repetition rate of the laser can be tuned flexibly from about 7 to 1100 GHz by controlling the optical path difference between the two arms of the MZI. The pulse duration can be reduced continuously from about 10.1 to 0.55 ps with the spectral width tunable from about 0.35 to 5.7 nm by manipulating the intracavity polarization controller. Numerical simulations well confirm the experimental observations and show that filter-driven four-wave mixing effect, induced by the MZI, is the main mechanism that governs the formation of the high-repetition-rate pulses. This all fiber-based laser is a simple and low-cost source for various applications where high-repetition-rate pulses are necessary. PMID- 24226152 TI - Influence of single nucleotide polymorphisms on thrombin generation in factor V Leiden heterozygotes. AB - Carriership of the factor V (FV) Leiden mutation increases the risk of venous thromboembolism (VTE) ~4-fold, but the individual risk of each FV Leiden carrier depends on several co-inherited risk and protective factors. Under the hypothesis that thrombin generation might serve as an intermediate phenotype to identify genetic modulators of VTE risk, we enrolled 188 FV Leiden heterozygotes (11 with VTE) and determined the following parameters: thrombin generation in the absence and presence of activated protein C (APC); plasma levels of prothrombin, factor X, antithrombin, protein S and tissue factor pathway inhibitor; and the genotypes of 24 SNPs located in the genes encoding these coagulation factors and inhibitors. Multiple regression analysis was subsequently applied to identify the (genetic) determinants of thrombin generation. The endogenous thrombin potential (ETP) showed a striking inter-individual variability among different FV Leiden carriers and, especially when measured in the presence of APC, correlated with VTE risk. Several SNPs in the F2 (rs1799963, rs3136516), F10 (rs693335), SERPINC1 (rs2227589), PROS1 (Heerlen polymorphism) and TFPI (rs5940) genes significantly affected the ETP-APC and/or the ETP+APC in FV Leiden carriers. Most of these SNPs have shown an association with VTE risk in conventional epidemiological studies, suggesting that the genetic dissection of thrombin generation leads to the detection of clinically relevant SNPs. In conclusion, we have identified several SNPs that modulate thrombin generation in FV Leiden heterozygotes. These SNPs may help explain the large variability in VTE risk observed among different FV Leiden carriers. PMID- 24226154 TI - Regeneration of fertile plants from protoplasts derived from embryogenic cell suspensions of barley (Hordeum vulgare L.). AB - We report regeneration of fertile plants from barley (Hordeum vulgare L. cv. Igri) protoplasts isolated from regenerable suspension cultures initiated from anther-derived embryogenic callus. Plants were routinely regenerated from these suspension cultures, which maintained their regenerative capacity for several months. It was first possible to isolate protoplasts from suspensions after three months of culture and after four months protoplasts capable of division could be isolated. Protoplasts maintained the regenerative capacity of the donor cells and formed embryogenic callus. Green plants were regenerated from protoplast-derived calli, although the proportion of albino plantlets was high. Viable regenerants were transferred to soil and fertile plants were recovered. PMID- 24226155 TI - Plantlet regeneration from encapsulated somatic embryos of hybrid Solanum melongena L. AB - High frequency somatic embryogenesis was induced from leaf expiants of F1 hybrid Solanum melongena L. on Murashige and Skoog's medium supplemented with 8.0 mg/1 NAA and 0.1 mg/1 Kn. The somatic embryos were encapsulated in various concentrations (2-6%) of sodium alginate and complexed with calcium chloride (25 100mM): 3% sodium alginate and 75 mM calcium chloride were found to be optimal for encapsulation. The encapsulated somatic embryos were transferred to various conversion media in vitro and in vivo. The frequency of plantlet regeneration varied from 27.0-49.7% in vitro and 2.0-4.5% in vivo. PMID- 24226156 TI - Regeneration of Gossypium hirsutum and G. barbadense from shoot apex tissues for transformation. AB - A method of regenerating cotton plants from the shoot apical meristem of seedlings was developed for use with particle gun and Agrobacterium-mediated transformation. This method was developed to circumvent the problems of genotype restriction and chromosomal damage frequently encountered in cotton regeneration in tissue culture through somatic embryogenesis. In this procedure, the cells of the shoot meristem are targeted for transformation. Normal and fertile plants of Gossypium barbadense Pima S-6, and 19 cultivars of G. hirsutum were regenerated using this method. Shoot regeneration from these tissues was direct and relatively rapid. A MS based, hormone-free medium could be used with all the varieties tested. PMID- 24226157 TI - Auxin-stimulated somatic embryogenesis from immature cotyledons of white clover. AB - Cotyledons from immature embryos of white clover (Trifolium repens L.) cv. Osceola were exposed to 2,4-D or NAA to induce somatic embryogenesis. NAA at 10 or 20 mg 1(-1) was very inefficient at stimulating embryogenesis, while concentrations of 30 or 40 mg 1(-1) resulted in death of the explant tissue. Continuous exposure of cotyledons to 40 mg 1(-1) 2,4-D resulted in somatic embryos which were arrested at the globular stage, or which underwent cycles of secondary embryogenesis, never proceeding beyond the globular stage. A 10 day exposure time to 2,4-D at the same concentration led to formation of somatic embryos, most of which had poorly developed cotyledons. Almost 10% of the somatic embryos converted into plants following transfer to medium devoid of growth regulators. Attempts to improve morphology of somatic embryos by using shorter exposure times to 2,4-D at 40 mg 1(-1), or by maintaining the 10 day exposure time while varying the concentration of 2,4-D, were not successful. Plants were obtained from all parents evaluated, although at different frequencies. PMID- 24226158 TI - Plant cell growth under different levels of oxygen and carbon dioxide. AB - An experimental system, in which gases of known composition were passed through flasks, was used to systematically study the effects of oxygen and carbon dioxide on plant cell growth. As expected, oxygen limiting conditions resulted in suppressed growth of Catharanthus roseus cultures. Oxygen limitations did not alter the amount of cell mass produced per gram of sugar consumed which suggests that the production of fermentative metabolites was limited. Varying levels of carbon dioxide were observed to have no effect on the growth rates of either C. roseus or Daucus carota cultures. The amount of C. roseus cell mass generated per gram of sugar consumed appeared to be slightly increased at higher carbon dioxide levels. PMID- 24226159 TI - Induction of catharanthine synthesis and stimulation of major indole alkaloids production by Catharanthus roseus cells under non-growth-altering treatment with Pythium vexans extracts. AB - A Catharanthus roseus cell line was selected that synthesised catharanthine exclusively under elicitation.From the first day of culture, treatment with very low concentrations of a Pythium extract did not alter the growth of the suspension but, within 24 hours, induced the synthesis of catharanthine and stimulated the production of ajmalicine. Kinetic analysis showed that serpentine then began to accumulate and that all of these effects lasted more than 7 days. Elicitation also induced changes in the cell/medium distribution of the alkaloids. Higher, although non-lethal, concentrations of the fungal elicitor were shown to impair alkaloid production. This cell line will serve as a model to study the conditions for the expression of catharanthine synthesis at the molecular level. PMID- 24226160 TI - Agrobacterium-mediated transformation of Solanum tuberosum L. cv. 'Russet Burbank'. AB - Stem sections from shoot cultures maintained in vitro were used to produce transgenic plants of the potato, Solanum tuberosum L. cv. 'Russet Burbank'. Stem internode pieces inoculated with Agrobacterium tumefaciens containing coat protein genes from potato virus X and potato virus Y, produced shoots with a frequency of 60% in the absence of selection and 10% on medium containing 100 mg/l kanamycin monosulfate. Regenerated shoots were assayed for kanamycin resistance by placing stem segments on callus induction medium containing an increased level of kanamycin. Of a total 255 regenerated shoots, 47 (18%) were kanamycin resistant. Of the kanamycin resistant shoots, 25 (53%) expressed the PVX or PVY coat protein genes as assayed by enzyme-linked immunosorbent assay or Western immunoblot analysis. PMID- 24226161 TI - Effect of abscisic acid and callus size on regeneration of american and international rice varieties. AB - Embryogenesis and plant regeneration of Texas and international rice, Oryza saliva (L.), varieties (both indica and japonica types) were induced in culture on a regime consisting of the use of ABA or BAP in the subculture medium and small (10 mg) callus pieces on the regeneration medium. Ten 10 mg callus pieces on regeneration medium resulted in a 2- to 10-fold increase in plant regeneration over single 100 mg pieces. Plant regeneration of Texas rice cultivars (Lemont, Rico I, Rexmont and Skybonnet) and Taipei 309 was enhanced by the use of ABA in the subculture medium with a 2-fold and a 3- to 10-fold increase in plant regeneration with 2.6 mgL(-1) and 26 mgL(-1) ABA in the subculture media, respectively. Regeneration of plants from callus of IR36 and IR64 was not enhanced by ABA but by the use of BAP and Trp in the subculture medium or by 2,4 D alone. The subculture medium containing BAP and Trp produced a 5-fold increase in plant regeneration rate from IR64 callus and was equal to subculture medium containing only 2,4-D for IR36 callus. Both Lemont and IR36 were previously reported to be difficult to regenerate or non-regenerative, however, the use of ABA or BAP in the subculture medium, small callus pieces and visual selection of embryogenic callus allowed the regeneration of up to 20 and 22 plants from 100 mg of Lemont and IR36 callus, respectively. PMID- 24226162 TI - Plantlet regeneration from immature cotyledon protoplasts of soybean (Glycine max L.). AB - Protoplasts were isolated from immature cotyledons of Glycine max L. Merr. cv. Clark 63 and cultured in liquid or in agarose-gelled modified KP8 medium. Plating efficiencies of 45-50% were obtained in liquid medium and 55-60% in 1.2% (w/v) agarose beads. Upon regular dilution with K8 medium rapidly growing green microcalli (1-2 mm in size) were obtained in 5-6 weeks, which upon transfer to MSB medium with 0.5 mg 1(-1) each of 2,4-D, BA, Kn and 500 mg 1(-1) CH produced compact green calli in 4-6 weeks. After 3-4 regular subcultures of 14 days each on MSB medium containing 0.5 mg 1(-1) each of BA, Kn, ZT, 0.1 mg 1(-1) NAA and 500 mg 1(-1) CH, about 21% of the compact calli formed multiple shoots. Addition of glutamine, asparagine and GA3 enhanced shoot regeneration up to 30%. Shoots of 0.5-1.0 cm length were transferred to 1/2 MS medium with 0.01 mg 1(-1) TH and 0.5 mg 1(-1) GA3 for elongation. In 2 to 3 weeks, approximately 60% of the shoots were 2-3 cm in length. These shoots were rooted on 1/2 MS with 1% sucrose and 0.2 mg 1(-1) IBA or 0.5 mg 1(-1) NAA. So far, twenty six plants have been transferred to the greenhouse, where they all have set seed. PMID- 24226163 TI - Selection of atrazine tolerant soybean calli and expression of that tolerance in regenerated plants. AB - Lines of soybean [Glycine max (L.)] tolerant of atrazine were developed by an in vitro and in vivo atrazine challenge. Cotyledonary node plus epicotyl explants from mature germinated seed of soybean introduction PI 438489B were cultured on RV-5 medium containing 48 mg active ingredient (a.i.)/l atrazine for one month. Most of the explants (66%) on medium containing atrazine, and 10% on medium without atrazine died. Explants surviving exposure to atrazine callused and organogenically regenerated shoots developed. Soil around R0 plants regenerated from atrazine tolerant shoots and nonatrazine challenged shoots (controls) were subsequently tested in vivo for atrazine tolerance. All controls died. Seeds were collected from atrazine tolerant R0 plants. Two weeks after planting, emerged R1 seedlings were tested in vivo for atrazine tolerance as the R0 plants were. This procedure was repeated on the R2 plants. All nonatrazine selected control plants died when exposed to this herbicide. Atrazine tolerant R2 plants were maintained in atrazine amended soil and appeared as healthy and vigorous as the control growing in atrazine free soil. PMID- 24226164 TI - In vitro induction of androgenic haploids in Safflower (Carthamus tinctorius L.). AB - The influence of culture medium on induction of androgenic calli was examined with five different basal media. MS medium was the most responsive in inducing callus. Differences in induction of calli among ten genotypes revealed that the most responsive genotype was a local cultivar, Mangira, with 48.6% anthers initiating callus formation. The influence of temperature pre-treatment (5 degrees +/-1 degrees C) for varying periods (0 to 15 days) on immature capitula prior to inoculation of anthers on the medium revealed that the percentage of anthers inducing callus increased till 3-5 days of pre-treatment. The effect of physiological conditions of anther donor plants grown in the field and in green houses on induction and re-differentiation have shown that the field grown anther donor plants exhibited optimum response. Shoot regeneration was observed on MS supplemented with BAP (2.0 mg/l) and NAA (0.5 mg/l) and rhizogenesis on MS (half strength) medium, supplemented with NAA (0.1 mg/l) and 1% sucrose. Cytological studies of anther derived plants showed two ploidy levels, where the haploids were predominant (64%). PMID- 24226165 TI - Effects of Pluronic F-68 on callus growth and protoplast plating efficiency of Solanum dulcamara. AB - The effects of the non-ionic surfactant, Pluronic F-68, on the growth of callus and protoplasts from Solanum dulcamara L. have been studied. Growth of callus was stimulated by addition of 0.1% (w/v) commercial grade Pluronic to culture medium, whereas lower concentrations (0.01% w/v) had no corresponding effect. In contrast, higher concentrations (1.0% w/v) of Pluronic inhibited callus growth. The mean plating efficiency of protoplasts grown at different densities (15 days after plating) was increased up to 26% following culture with 0.1% (w/v) Pluronic, while 0.01% (w/v) Pluronic was ineffective. Mean protoplast plating efficiency decreased by up to 32% following culture with 1.0% (w/v) Pluronic. PMID- 24226167 TI - Lewis base-catalyzed reactions of cyclopropenones: novel synthesis of mono- or multi-substituted allenic esters. AB - The reactions of cyclopropenones with nucleophiles (H2O or methanol) could be catalyzed by nitrogen-containing Lewis bases or phosphorus-containing Lewis bases, affording the corresponding mono- or multi-substituted allenic esters in moderate to excellent yields. PMID- 24226166 TI - Genome scale transcriptomics of baculovirus-insect interactions. AB - Baculovirus-insect cell technologies are applied in the production of complex proteins, veterinary and human vaccines, gene delivery vectors' and biopesticides. Better understanding of how baculoviruses and insect cells interact would facilitate baculovirus-based production. While complete genomic sequences are available for over 58 baculovirus species, little insect genomic information is known. The release of the Bombyx mori and Plutella xylostella genomes, the accumulation of EST sequences for several Lepidopteran species, and especially the availability of two genome-scale analysis tools, namely oligonucleotide microarrays and next generation sequencing (NGS), have facilitated expression studies to generate a rich picture of insect gene responses to baculovirus infections. This review presents current knowledge on the interaction dynamics of the baculovirus-insect system' which is relatively well studied in relation to nucleocapsid transportation, apoptosis, and heat shock responses, but is still poorly understood regarding responses involved in pro-survival pathways, DNA damage pathways, protein degradation, translation, signaling pathways, RNAi pathways, and importantly metabolic pathways for energy, nucleotide and amino acid production. We discuss how the two genome-scale transcriptomic tools can be applied for studying such pathways and suggest that proteomics and metabolomics can produce complementary findings to transcriptomic studies. PMID- 24226168 TI - Relationship between wave reflection and renal damage in hypertensive patients: a retrospective analysis. AB - OBJECTIVE: Arterial stiffening has harmful effects; peripheral pulse wave reflections deleteriously increase central pressure, but on the contrary they could also possibly be protective, as the pulse is transmitted to the microcirculation to a lesser extent. The aim of this study was, therefore, to explore the relationship between wave reflection and small vessel damage in the kidney. METHODS: In 216 hypertensive patients, data on renal resistive index, obtained by Doppler ultrasound sampling of the interlobar arteries, as well as augmentation index (AIx) and carotid-to-femoral pulse wave velocity (PWV), were retrospectively analyzed. Reflection magnitude was computed through a triangular flow estimate. RESULTS: AIx and reflection magnitude were positively correlated with resistive index; age, BMI, central pulse pressure, and cholesterol, but not AIx or reflection magnitude, were predictors of resistive index in multivariate analyses. Crossing tertiles of PWV and AIx, resistive index did not differ between patients with high AIx and low PWV (n=25; 0.632 (0.064)) and those with low AIx and high PWV (n=17; 0.645 (0.053)), despite a difference in reflection magnitude (74.9 (6.7) vs. 51.2 (7.3)%; P<0.001). CONCLUSION: Pressure wave reflection is positively correlated with resistive index in a hypertensive population. No negative relationship was found even adjusting for confounders or when it was examined separately from the influence of arterial stiffness. These findings do not support the hypothesis of peripheral wave reflections having a significant protective role for the microcirculation of a low resistance vascular bed such as the kidney. PMID- 24226169 TI - Orthodontic treatment for prominent upper front teeth (Class II malocclusion) in children. AB - BACKGROUND: Prominent upper front teeth are a common problem affecting about a quarter of 12-year old children in the UK. The correction of this condition is one of the most common treatments performed by orthodontists. This condition develops when the child's permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. These teeth are more likely to be injured and their appearance can cause significant distress.If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. OBJECTIVES: To assess the effects of orthodontic treatment for prominent upper front teeth when this treatment is initiated when the child is seven to 11 years old compared to when they are in early adolescence, or when treatment uses different types of orthodontic braces. SEARCH METHODS: We searched the following databases: Cochrane Oral Health Group's Trials Register (to 17 April 2013), CENTRAL (The Cochrane Library 2013, Issue 3), MEDLINE (OVID) (1946 to 17 April 2013) and EMBASE (OVID) (1980 to 17 April 2013). There were no restrictions regarding language or publication date. SELECTION CRITERIA: Randomised controlled trials of children and/or adolescents (age < 16 years) on early treatment (either one or two-phase) with any type of orthodontic braces (removable, fixed, functional) or head-braces compared with late treatment with any type of orthodontic braces or head-braces; or, on any type of orthodontic braces or head braces compared with no treatment or another type of orthodontic brace or appliance (with treatment starting in children of similar ages in both groups) to correct prominent upper front teeth. DATA COLLECTION AND ANALYSIS: Review authors screened the search results, extracted data and assessed risk of bias independently, used odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous outcomes, mean differences (MDs) and 95% CIs for continuous outcomes and a fixed-effect model for meta-analyses as there were fewer than four studies. MAIN RESULTS: We included 17 studies based on data from 721 participants.Three trials (n = 343) compared early (two-phase) treatment (7-11 years of age) with a functional appliance, with adolescent (one-phase) treatment. Statistically significant differences in overjet, ANB and PAR scores were found in favour of functional appliance when the first phase of early treatment was compared with observation in the children due to receive treatment in adolescence. However, at the end of treatment in both groups, there was no evidence of a difference in the overjet (MD 0.21, 95% CI -0.10 to 0.51, P = 0.18) (low quality evidence), final ANB (MD -0.02, 95% CI -0.47 to 0.43, P = 0.92), PAR score (MD 0.62, 95% CI -0.66 to 1.91, P = 0.34) or self concept score (MD 0.83, CI -2.31 to 3.97, P = 0.60). However, two-phase treatment with functional appliance showed a statistically significant reduction in the incidence of incisal trauma (OR 0.59, 95% CI 0.35 to 0.99, P = 0.04) (moderate quality evidence). The incidence of incisal trauma was clinically significant with 29% (54/185) of patients reporting new trauma incidence in the adolescent (one-phase) treatment group compared to only 20% (34/172) of patients receiving early (two-phase) treatment.Two trials (n = 285), compared early (two-phase) treatment using headgear, with adolescent (one-phase) treatment. Statistically significant differences in overjet and ANB were found in favour of headgear when the first phase of early treatment was compared with observation in the children due to receive treatment in adolescence. However, at the end of treatment in both groups, there was no evidence of a difference in the overjet (MD 0.22, 95% CI -0.56 to 0.12, P = 0.20) (low quality evidence), final ANB (MD -0.27, 95% CI -0.80 to 0.26, P = 0.32) or PAR score (MD -1.55, 95% CI 3.70 to 0.60, P = 0.16). The incidence of incisal trauma was, however, statistically significantly reduced in the two-phase treatment group (OR 0.47, 95% CI 0.27 to 0.83, P = 0.009) (low quality evidence). The adolescent treatment group showed twice the incidence of incisal trauma (47/120) compared to the young children group (27/117).Two trials (n = 282) compared different types of appliances (headgear and functional appliance) for early (two-phase) treatment. At the end of the first phase of treatment statistically significant differences, in favour of functional appliances, were shown with respect to final overjet only. At the end of phase two, there was no evidence of a difference between appliances with regard to overjet (MD -0.21, 95% CI -0.57 to 0.15, P = 0.26), final ANB (MD -0.17, 95% CI -0.67 to 0.34, P= 0.52), PAR score (MD -0.81, 95% CI 2.21 to 0.58, P = 0.25) or the incidence of incisal trauma (OR 0.79, 95% CI 0.43 to 1.44, P = 0.44).Late orthodontic treatment for adolescents with functional appliances showed a statistically significant reduction in overjet of -5.22 mm (95% CI -6.51 to -3.93, P < 0.00001) and ANB of -2.37 degrees (95% CI -3.01 to 1.74, P < 0.00001) when compared to no treatment (very low quality evidence).There was no evidence of a difference in overjet when Twin Block was compared to other appliances (MD 0.01, 95% CI -0.45 to 0.48, P = 0.95). However, a statistically significant reduction in ANB (-0.63 degrees , 95% CI -1.17 to 0.08, P = 0.02) was shown in favour of Twin Block. There was no evidence of a difference in any reported outcome when Twin Block was compared with modifications of Twin Block.There was insufficient evidence to determine the effects of Activator, FORSUS FRD EZ appliances, R-appliance or AIBP. AUTHORS' CONCLUSIONS: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is more effective in reducing the incidence of incisal trauma than providing one course of orthodontic treatment when the child is in early adolescence. There appears to be no other advantages for providing treatment early when compared to treatment in adolescence. PMID- 24226170 TI - Long-term statin use and risk of breast cancer--letter. PMID- 24226171 TI - Local perceptions on factors influencing the introduction of international healthcare accreditation in Pakistan. AB - One contributor to poor health outcomes in developing countries is weak health systems; key to strengthening them are interventions to improve quality of health services. Though the value of healthcare accreditation is increasingly recognized, there are few case studies exploring its adaptation in developing countries. The aim of our study in Pakistan was to identify perceived factors influencing the adaptation of international healthcare accreditation within a developing country context. We used qualitative methods including semi-structured interviews, a structured group discussion, focus groups and non-participant observation of management meetings. Data analysis used a grounded theory approach and a conceptual framework adapted from implementation science. Using our conceptual framework categories of 'inner' and 'outer' setting, we found six perceived inner health system factors that could influence the introduction of healthcare accreditation and two 'outer' setting factors, perceived as external to the health system but able to influence its introduction. Our research identified that there is no 'one size fits all' approach to introducing healthcare accreditation as a means to improve healthcare quality. Those planning to support healthcare accreditation, such as national and provincial ministries and international development partners, need to understand how the three components of healthcare accreditation fit into the local health system and into the broader political and social environment. In our setting this included moving to supportive and transparent external evaluation mechanisms, with a first step of using locally developed and agreed standards. In addition, sustainable implementation of the three components was seen as a major challenge, especially establishment of a well-managed, transparent accreditation agency able to lead processes such as training and support for peer surveyors. Consideration of local change mechanisms and cultural practices is important in designing a local accreditation approach. The results of our study are important for health systems strengthening in Pakistan and in other developing countries. PMID- 24226172 TI - Absence of ribosomes in Capsicum chromoplasts. AB - Ribosome development was followed by electron microscopy and gel electrophoresis of ribosomal (r)RNAs in the plastids of fully expanded fruits of Capsicum annuum L. during ripening. Chloroplasts from young Capsicum leaves were used as a structural and electrophoretic standard. Four stages were distinguished on the basis of colour changes during fruit ripening. Chloroplasts of the green fruit had a lower content of 16S and 23S rRNAs than leaf chloroplasts. They contained only a few ribosomes, some more discrete "ribosomal particles", and the contrast of ribosomal structures was faint. From the outset of ripening, most of the ribosomal structures in the plastid stroma disappeared. A continuous decrease in plastid rRNAs occurred during ripening. Fully differentiated chromoplasts of the red fruit did not contain rRNAs or ribosomes. Throughout plastid development, DNA nucleoids were evident and there was only a small decrease in the DNA peak on electrophoretograms. The loss of ribosomes during the chloroplast-to-chromoplast conversion in Capsicum fruit is discussed in relation to the variations in pigments and enzymic systems in both plastid types. PMID- 24226173 TI - Immunological characterization of chlorophyll a/b-binding proteins of barley thylakoids. AB - Monoclonal antibodies have been raised against the light-harvesting chlorophyll a/b-binding proteins of photosystem I (LHCI) using a photosystem (PS) I preparation (PSI-200) wild-type from barley (Hordeum vulgare L. cv. Svalof's Bonus) as the antigen. These antibodies cross-reacted with a minor light harvesting chlorophyll a/b-protein of PSII (Chla/b-P1=CP29), but not with the major one, LHCII (=Chla/b-P2(**)). Similarly, a monoclonal antibody to Chla/b-P1, elicited by a PSII preparation as the antigen, cross-reacted with LHCI, but not LHCII. This explains why an antigen consisting of LHCII, free of LHCI, but contaminated with Chla/b-P1, can elicit antibodies which cross-react with LHCI. Immunoblot assays showed that LHCI and Chla/b-P1 have at least two epitopes in common. Immunogold labelling of thin-sectioned wild-type thylakoids confirmed a preferential localisation of Chla/b-P1 in grana partition membranes and LHCI in stroma lamellae. The presence of LHCI was demonstrated in barley mutants lacking the PSI reaction centre (viridis-zb (63)) and chlorophyll b (chlorina-f2), and was correlated with the presence of long-wavelength (730 nm) fluorescence emission at 77 K. The mutant viridis-k (23), which has a 77 K long-wavelength fluorescence peak at 720 nm, was shown by immune-blot assay to lack LHCI, although Chla/b-P1 was present. PMID- 24226174 TI - Spatial relationship between microtubules and plasma-membrane rosettes during the deposition of primary wall microfibrils in Closterium sp. AB - The mechanism by which cortical microtubules (MTs) control the orientation of cellulose microfibril deposition in elongating plant cells was investigated in cells of the green alga, Closterium sp., preserved by ultrarapid freezing. Cellulose microfibrils deposited during formation of the primary cell wall are oriented circumferentially, parallel to cortical MTs underlying the plasma membrane. Some of the microfibrils curve away from the prevailing circumferential orientation but then return to it. Freeze-fracture electron microscopy shows short rows of particle rosettes on the P-face of the plasma membrane, also oriented perpendicular to the long axis of the cell. Previous studies of algae and higher plants have provided evidence that such rosettes are involved in the deposition of cellulose microfibrils. The position of the rosettes relative to the underlying MTs was visualized by deep etching, which caused much of the plasma membrane to collapse. Membrane supported by the MTs and small areas around the rosettes resisted collapse. The rosettes were found between, or adjacent to, MTs, not directly on top of them. Rows of rosettes were often at a slight angle to the MTs. Some evidence of a periodic structure connecting the MTs to the plasma membrane was apparent in freeze-etch micrographs. We propose that rosettes are not actively or directly guided by MTs, but instead move within membrane channels delimited by cortical MTs attached to the plasma membrane, propelled by forces derived from the polymerization and crystallization of cellulose microfibrils. More widely spaced MTs presumably allow greater lateral freedom of movement of the rosette complexes and result in a more meandering pattern of deposition of the cellulose fibrils in the cell wall. PMID- 24226175 TI - Protein bodies in ray cells of Populus x canadensis Moench 'robusta'. AB - Light- and electron-microscopical investigations revealed distinct intravacuolar protein aggregates of 0.3-0.8 MUm in diameter in ray cells of poplar during the dormant season. In semi-thin sections, these bodies showed positive protein staining and enzymatic digestibility with pepsin, indicating their proteinaceous nature. Morphometric measurements showed such protein bodies in 7-13% of the area of the ray-cell lumen. This amount corresponded with the protein content of the wood determined biochemically, e.g. 2.0-5.0 MUg.mg(-1) dry weight. Polyacrylamide gel electrophoresis of the total protein fraction extracted from wood showed prominent polypeptide species with an apparent molecular weight of 30-32 kilodaltons. The results indicate considerable protein storage in ray cells, especially in the form of protein-storage vacuoles. PMID- 24226176 TI - Plasmatubules in the pollen tubes of Nicotiana sylvestris. AB - Ultrastructural studies of the pollen tubes of Nicotiana sylvestris grown in the pistil revealed an extensive development of plasmatubules formed by evaginations of the plasma membrane. The plasmatubules occurred as twisted tubular structures in the periplasmic space along the tube wall and, in cross section, exhibited circular profiles with an outer diameter of 28+/-4 nm. They were also seen in deep, pocket-like invaginations of the plasma membrane and in this case the profiles had an outer diameter of 34+/-8 nm. In the pocket-like invaginations they were partially branched and often closely packed to form groups with obvious patterns. The enlargement of the plasma-membrane area resulting from plasmatubules formed along the tube wall was about six-to tenfold. Pollen tubes grown in vitro exhibited poorly developed plasmatubules. It is suggested that the large extension of the plasma membrane could enhance the uptake of nutrients, and thus might be responsible for the comparatively fast growth of pollen tubes in the pistil. Moreover, it is also assumed that the turnover rate of the Golgi apparatus must be higher in pollen tubes growing in vivo than in vitro, in order to provide a sufficient amount of membrane for the formation of the plasma membrane with its tubular modifications. PMID- 24226177 TI - The effect of red and far-red light on proton secretion from mesophyll-cell protoplasts of Vicia faba L. AB - The influence of red and far-red irradiation on the transport of H(+) and (86)Rb(+) through the plasmalemma was studied using parenchymal protoplasts isolated from Vicia faba leaves. The results indicate that red light stimulates H(+) secretion and the uptake of (86)Rb(+). Moreover, it has been demonstrated that far-red irradiation acts antagonistically with respect to red light in both these processes. PMID- 24226178 TI - An endogenous RNA-synthesis-promoting oligopeptide from Cucurbita pepto var. patissonina. AB - The effect of CPPTI (Cucurbita pepo patissonina trypsin inhibitor) on the growth of Cucurbita pepo var patissonina (White bush) was examined. Plants treated with CPPTI grew faster than untreated plants and similarly to those treated with gibberellic acid. Isolated cell nuclei from plants treated with CPPTI showed that of the three DNA-dependent RNA polymerases assayed, RNA polymerase I (EC2.7.7.6) activity was preferentially elevated. PMID- 24226179 TI - Development of nitrogen-assimilating enzymes in sunflower cotyledons during germination as affected by the exogenous nitrogen source. AB - Activities of nitrate reductase (NR; EC 1.6.6.1), nitrite reductase (NiR; EC 1.7.7.1), glutamine synthetase (GS; EC 6.3.1.2) and glutamate dehydrogenase (GDH; EC 1.4.1.3) were measured in cotyledons of sunflower (Helianthus annuus L. cv Peredovic) seedlings during germination and early growth under various external nitrogen sources. The presence of NO 3 (-) in the medium promoted a gradual increase in the levels of NR and NiR activities during the first 7 d of germination. Neither NR nor NiR activities were increased in a nitrogen-free medium or in media with either NH 4 (+) or urea as nitrogen sources. Moreover, the presence of NH 4 (+) did not abolish the NO 3 (-) -dependent appearance of NR and NiR activities. The increase of NR activity was impaired both by cycloheximide and chloramphenicol, which indicates that both cytoplasmic 80S and plastidic 70S ribosomes are involved in the synthesis of the NR molecule. By contrast, the appearance of NiR activity was only inhibited by cycloheximide, indicating that NiR seems to be exclusively synthesized on the cytoplasmic 80S ribosomes. Glutamine-synthetase activity was also strongly increased by external NO 3 (-) but not by NH 4 (+) or urea. The appearance of GS activity was more efficiently suppressed by cycloheximide than chloramphenicol. This indicates that GS is mostly synthesized in the cytoplasm. The cotyledons of the dry seed contain high levels of GDH activity which decline during germination independently of the presence or absence of a nitrogen source. Cycloheximide, but not chloramphenicol, greatly prevented the decrease of GDH activity. PMID- 24226180 TI - In vitro synthesis of the cyanelle proteins of Cyanophora paradoxa by isolated cyanelles and cyanelle RNA. AB - Cyanelles isolated from the alga Cyanophora paradoxa Korschikoff synthesized cyanelle proteins in vitro. This synthesis was stimulated by light and totally inhibited by chloramphenicol. Cycloheximide had only a small inhibitory effect. Electrophoretic separation of the labelled soluble cyanelle proteins yielded at least 20 discrete polypeptides. The RNA isolated from the cyanelles and the whole cells was successfully translated in a rabbit reticulocyte-lysate system. PMID- 24226181 TI - Cross-reactivity of monoclonal antibodies against phytochrome from Zea and Avena : Localization of epitopes, and an epitope common to monocotyledons, dicotyledons, ferns, mosses, and a liverwort. AB - The cross-reactivity of diverse monoclonal antibodies against phytochrome from Zea and Avena was tested by enzyme-linked immunosorbentassay (ELISA) and by immunoblotting. About 40 antibodies were selected by means of nondenatured phytochrome; all of them reacted with sodium dodecyl sulfate denatured homologous antigen on immunoblots. The epitopes for 14 antibodies (4 raised against Avena and 10 against Zea phytochrome) were localized in 6 regions of the phytochrome molecule by means of Western blot analysis of proteolytic fragments of known localization. Results of studies on the inhibition of antibody binding by other antibodies were largely compatible with these latter findings. Except in a few cases, inhibition occurred when antibodies were located on the same or a closely adjacent region. As demonstrated by 16 species, cross-reactivity with phytochromes from other Poaceae was high. Greater losses in cross-reactivity were observed only with antibodies recognizing an epitope in the vicinity of the carboxyl terminus of 118-kg . mol(-1) phytochrome. Cross-reactivity with phytochrome from dicotyledons was restricted to a few antibodies. However, phytochrome(s) from plants illuminated for 24 h or more could be detected. One of the antibodies that recognized phytochrome from dicotyledons was also found to recognize phytochrome or a protein of 120-125 kg.mol(-1) from several ferns, a liverwort and mosses. This antibody (Z-3B1), which was localized within a 23.5 kg.mol(-1) section of Avena phytochrome (Grimm et al., 1986, Z. Naturforsch. 41c, 993), seems to be the first antibody raised against phytochrome from a monocotyledon with such a wide range of reactivity. Even though epitopes were recognized on different phytochromes, the strength of antibody binding indicated that these epitopes are not necessarily wholly identical. PMID- 24226182 TI - Isolation and characterization of a barley mutant with abscisic-acid-insensitive stomata. AB - A barley (Hordeum vulgare L.) mutant ("cool") with leaf transpiration unaffected by the application of 1 mM abscisic acid (ABA) was isolated from the population of M2 seedlings using thermography (electronic visualization, and quantitation of the temperature profiles on the surface of the leaves). Stomata of the mutant plants were insensitive to exogenously applied ABA, darkness, and such desiccation treatments as leaf excision and drought stress. The evaporative cooling of the leaves of the "cool" barley was always higher than that of the wild-type barley, even without ABA application, indicating that the diffusive resistance of the mutant leaves to water loss was always lower. Guard-cell morphology and stomatal density as well as ABA level and metabolism were seemingly unaltered in the mutant plants. In addition, gibberellin-induced alpha amylase secretion and precocious embryo germination in the mutant barley was inhibited by ABA to the same extent as in the wild-type barley. PMID- 24226183 TI - Rapid elicitation of second messengers by nanomolar doses of triacontanol and octacosanol. AB - Triacontanol (TRIA) increases the dry weight and alters the metabolism of rice (Oryza sativa L.) seedlings within 10 min of application to either the shoots or roots. This activity is prevented if octacosanol (OCTA, C28 primary alcohol) is applied with the TRIA on the roots or shoots. Triacontanol activity is also stopped if the OCTA is applied at least 1 min before the TRIA on the opposite part of the seedling.Triacontanol rapidly elicits a second messenger that moves rapidly throughout the plant resulting in stimulation of growth (dry-weight increase) and water uptake. Octacosanol also produces a second messenger that inhibits TRIA activity. We have named the putative secondary messengers elicited by TRIA and OCTA, TRIM and OCTAM, respectively. The water-soluble TRIM extracted from plants treated with TRIA increases the growth of rice seedlings about 50% more than extracts from untreated plants, within 24 h of application. Both OCTAM and OCTA inhibit the activity of TRIA but not of TRIM.The TRIA messenger was isolated from rice roots within 1 min of a foliar application of TRIA. The TRIM elicited by TRIA will pass through a 4-mm column of water connecting cut rice shoots with their roots and can also be recovered from water in which cut stems of TRIA-treated plants have been immersed. Triacontanol applied to oat (Avena sativa L.) or tomato (Lycopersicon esculentum Mill.) shoots connected to rice roots by a 4-mm water column also results in the appearance of TRIM in rice roots. PMID- 24226184 TI - Induced net Ca(2+) uptake and callose biosynthesis in suspension-cultured plant cells. AB - In suspension-cultured cells of Glycine max and Catharanthus roseus, marked callose synthesis can be induced by digitonin and chitosan. Leakage of a limited pool of electrolytes precedes callose formation, K(+) representing the major cation lost. Poly-L-ornithine, as well as the ionophores A 23187 and ionomycin, also induces some callose synthesis but to a lesser extent. Digitonin increases the net uptake of Ca(2+) from the external buffer with a time course parallel to callose synthesis but lagging behind the leakage of K(+). Nifedipine partly blocks callose synthesis as well as the digitonin-induced increase in net Ca(2+) uptake. Taken together, the data support the hypothesis that addition of the various substances might indirectly lead to membrane perturbation causing the common event of an increase in net Ca(2+) uptake which results in callose deposition by a direct activition of the Ca(2+)-dependent and plasma-membane located 1,3-beta-glucan synthase. PMID- 24226186 TI - Metabolism and compartmentation of dihydrozeatin exogenously supplied to photoautotrophic suspension cultures of Chenopodium rubrum. AB - [(3)H]Dihydrozeatin supplied to photoautotrophically growing cell suspension cultures of Chenopodium rubrum was rapidly taken up and metabolized by the cells. The predominant metabolites in extracts of the cells were [(3)H]dihydrozeatin-O glucoside and [(3)H]dihydrozeatin riboside-O-glucoside. Both these compounds could be shown to be compartmented within the vacuole, whereas [(3)H]dihydrozeatin and [(3)H]dihydrozeatin riboside, which were both present to a minor extent in cell extracts, were both present to a minor extent in cell extracts, were localized predominantly outside the vacuole. Analysis of the culture medium at the end of the 36-h incubation period showed that there had been an efflux of [(3)H]dihydrozeatin metabolites out of the cells. Whereas [(3)H]dihydrozeatin riboside was found to be the major extracellular [(3)H]dihydrozeatin metabolite, the O-glucosides of neither this compound nor [(3)H]dihydrozeatin could be detected in the medium. The differential compartmentation of [(3)H]dihydrozeatin metabolites found with the C. rubrum suspension-culture system is discussed with respect to possible mechanisms governing the metabolism of cytokinins in plants cells. PMID- 24226185 TI - Uridine 5'-diphospho-D-glucose-dependent vectorial sucrose synthesis in tonoplast vesicles of the storage hypocotyl of red beet (Beta vulgaris L. ssp. conditiva). AB - Tonoplast vesicles were prepared from red-beet (Beta vulgaris L. ssp. conditiva) hypocotyl tubers ("beetroot") known to store sucrose. Uptake experiments, employing uridine 5'-diphospho-[(14)C]glucose (UDP-[(14)C]glucose) showed the operation of an UDP-glucose-dependent group translocator for vectorial synthesis and accumulation of sucrose, recently described for sugarcane and red-beet vacuoles and for tonoplast vesicles prepared from sugarcane suspension cells. Characterization of the kinetic properties yielded the following results. Uptake of UDP-glucose was linear for 15 min. The apparent K m was 0.75 mM for UDP glucose (at pH 7.2, 1 mM Mg(2+)), V max was 32 nmol.(mg protein)(-1).min(-1). The incorporation of UDP-glucose exhibited a sigmoidal substrate-saturation curve in the absence of Mg(2+), the Hill coefficient (n H) was 1.33; Michaelis-Menten kinetics were obtained, however, in the presence of 1 mM MgCl2. For the reaction sequence under the control of the group translocator a dual pH optimum was found at pH 7.2 and 7.9, respectively. All reaction intermediates and the end product sucrose could be identified by two-dimensional high-performance thin-layer chromatography and autoradiography. The distribution pattern of radioactivity showed almost uniformly high labeling of all intermediates and sucrose. The physiological relevance of the results is discussed in the light of the fact that the tonoplast of red-beet storage cells accommodates two mechanisms of sucrose uptake (i) vectorial sucrose synthesis and (ii) direct ATP-dependent sucrose assimilation. PMID- 24226187 TI - Determination of endogenous abscisic acid levels in immature cereal embryos during in vitro culture. AB - Levels of endogenous abscisic acid (ABA) in immature wheat (Triticum aestivum cv. Timmo) and barley (Hordeum vulgare cv. Golden Promise) embryos have been determined by enzyme-linked immunosorbent assay. Embryos of both cereal species showed an increase in ABA content during development on the parent plant. Immature embryos were excised and cultured in vitro on nutrient media that led to precocious germination or on media containing 9% (w/v) mannitol that maintained their developmental arrest. Barley and wheat embryos responded to these culture conditions in an identical manner with respect to changes in morphology, fresh weight, protein and lectin content. However, in complete contrast, the ABA content of barley embryos increased by an order of magnitude during culture on mannitol, whereas that of wheat embryos showed no significant change. The results are discussed within the context of the role of ABA in the regulation of embryo development. PMID- 24226188 TI - Model of gas exchange and diffusion in legume nodules : I. Calculation of gas exchange rates and the energy cost of N2 fixation. AB - A mathematical model is described which allows the estimation of rates of O2, CO2, N2, and H2 exchange from legume nodules under steady state conditions of N2 fixation. Calculated rates of gas exchange under defined conditions of nodule size, relative growth rate (RGR), specific total nitrogenase activity (TNA), nitrogenase electron allocation coefficient (EAC), uptake-hydrogenase activity (HUP) and nature of the N export product compared favorably with experimentally obtained rates reported in the literature. Therefore the model was used to predict the effects of varying each of these nodule characteristics on the rates of gas exchange, and on the apparent respiratory cost (CO2/NH3) and sucrose cost (sucrose consumed/NH3) of N2 fixation.The model predicted that, all other characters being equal, ureide-producing nodules would consume 8% less sucrose per N fixed than asparagine-producing nodules, but would display an apparent respiratory cost which would be 5% higher than that in asparagine-producing nodules. In both ureide-producing and asparagine-producing nodules, the major factor affecting the apparent respiratory cost of N2 fixation was predicted to be EAC, followed by TNA, nodule RGR and nodule size. The relative importance of HUP in improving the apparent respiratory cost of N2 fixation was predicted to be largely dependent upon its potential role in the regulation of EAC. PMID- 24226189 TI - Model of gas exchange and diffusion in legume nodules : II. Characterisation of the diffusion barrier and estimation of the concentrations of CO2, H 2 and N 2 in the infected cells. AB - The rates of nodule O2, CO2, N2 and H2 exchange calculated in the previous modeling study (D.B. Layzell et al., 1987, Planta 173, 117-127) were combined with information on the diffusion characteristics of each gas, and the structural characteristics of soybean nodules, to produce a comprehensive mathematical model of nodule structure and function. The model assumed that an aqueous barrier to gas diffusion exists in the nodule cortex which may be regulated to maintain an O2 concentration of 10 nM in the centre of the infected cells of the central zone. The model was used to predict the concentration of N2, CO2 and H2 in the infected cells as the physical and physiological characteristics of the nodule were varied. The model predicted that (a) the diffusion barrier may be represented by plugs of water in the intercellular spaces of a layer of cells between the inner and outer cortex, the depth of which may be varied to vary the resistance of the barrier; (b) facilitated diffusion of O2 by oxyleghemoglobin is essential to the regulation of free O2 concentration in the infected cells; (c) the diffusion barrier is less effective in regulating CO2 flux than the fluxes of other gases with the result that the total gas pressure in the central zone is less than atmospheric pressure; (d) concentrations of N2 and HCO 3 (-) in the infected cells are saturating with respect to nitrogenase activity and phosphoenolpyruvate carboxylase activity respectively and (e) under atmospheric conditions the concentration of H2 in the infected cells is similar to, or greater than the K i . (H2) for N2 fixation, which may account for values of nitrogenase electron allocation coefficient below 0.75. PMID- 24226191 TI - Selective photocatalytic conversion of glycerol to hydroxyacetaldehyde in aqueous solution on facet tuned TiO2-based catalysts. AB - Glycerol is selectively converted to hydroxyacetaldehyde (HAA) and H2 in aqueous solution on TiO2-based photocatalysts. The product selectivity was verified to be strongly dependent on the facets of TiO2. Rutile with high percentage of {110} facets results in over 90% superior selectivity of HAA, while anatase with {001} or {101} facets gives only 16% and 49% selectivity for HAA, respectively. PMID- 24226192 TI - Signalling: Finding the GAPs in mTORC1 signalling. PMID- 24226194 TI - The interface between physical and mental disorders: The need to dismantle the biopsychosocialneuroimmunological model of disease. AB - This article argues for the necessity of cognitive-behavioral assessment for a thorough understanding of how psychological factors mediate disease process across a wide range of diseases including coronary artery disease, breast cancer, and human immunodeficiency disease. Based on empirical data presented as part of the APA Presidential miniconvention, "To Your Health: Psychology through the Life Span," the conclusion is that psychological treatment can help extend life. Stress management programs can positively influence adherence to treatment regimens and positively influence the human immune system response during the course of treatment and recovery from illness. Even in the face of life threatening circumstances such as liver transplantation, Stage II and III breast cancer, and after HIV infection has been diagnosed, the quality of life can be remarkably improved. Physicians and psychologists must work together to produce the beneficial effects of the synergy between mind-body processes. PMID- 24226195 TI - Hypertension and cognitive function. AB - Previous research indicates that blood pressure may impact a variety of cognitive functions, including short-term memory, abstract reasoning, visual-spatial abilities, and attention (Boller, Vrtunski, Mack, & Kim, 1977; Elias, Robbins, Schultz, & Pierce, 1990; Franceschi, Tancredi, Smirne, Mercinelli, & Canal, 1982; Mazzucchiet al., 1986). However, studies which have assessed the cognitive functioning of hypertensive adults have offered conflicting results, particularly when hypertension levels were in the mild range (e.g., Bolleret al., 1977; Eliaset al., 1990; Elias, Wolf, D'Agostino, Cobb, & White, 1993; Farmeret al., 1987, 1990; Franceschiet al., 1982; Perez-Stable, Coates, Halliday, Gardiner, & Hauck, 1992; Schmidtet al., 1991; Waldstein, Ryan, Manuck, Parkinson, & Bromet, 1991). A number of factors may contribute to the inconsistent findings in this area. Researchers have employed a wide range of neuropsychological instruments to assess varying domains of cognitive function. Sample sizes in some studies have been too small to ensure sufficient power. Finally, studies have employed varying methodological control over potential confounding factors such as concurrent medical conditions, alcohol abuse, psychiatric disorders, or antihypertensive medication. This study compared male veterans with blood pressures in the mildly hypertensive range (n=166) to normotensive veterans (n=176) on neuropsychological measures of verbal fluency, visual-spatial ability, verbal and visual memory, dexterity, attention, and executive functions. Results revealed that, after controlling for differences in education and income, there was no relationship between mild hypertension and combined measures of cognitive performance. The present findings suggest that mild hypertension alone has little effect on cognitive function in adults. PMID- 24226196 TI - The relationship among the transtheoretical model of behavioral change, psychological distress, and diet attitudes in obesity: Implications for primary care intervention. AB - Obesity is prevalent but undertreated in primary care. Family practice volunteer outpatients (N=454) were administered the Stage of Change for Weight (URICA), the Brief Symptom Inventory (BSI), and the Diet Readiness Test (DRT) to assess the relationship between these variables and obesity. The body mass index (BMI) was used to classify obesity revealing 197 patients with elevated BMI's. There was no significant difference between the obese and the nonobese on any of the psychological measures. The obese reported significantly more difficulty setting diet goals and less control over their eating, ate more to emotional situations, and exercised less than the nonobese. The obese sample (46.7%) reported being in the Action stage of change for weight management. Implications for intervention in primary care include targeting attitudes (DRT) and dispelling physician attitudes that obese individuals have increased levels of psychological distress. Addressing Stage of Change for weight management can facilitate tailoring the appropriate intervention when used in concert with the DRT variables. PMID- 24226197 TI - Mental health treatment and medical utilization: First pilot study in the military. AB - Savings in medical utilization, as a function of psychotherapeutic intervention, which has been widely demonstrated elsewhere, can be replicated in military medical settings. Results point not only to decreased medical utilization following mental health intervention, but also to more appropriate treatment. PMID- 24226193 TI - Immunity, inflammation and cancer: a leading role for adenosine. AB - Cancer is a complex disease that is dictated by both cancer cell-intrinsic and cell-extrinsic processes. Adenosine is an ancient extracellular signalling molecule that can regulate almost all aspects of tissue function. As such, several studies have recently highlighted a crucial role for adenosine signalling in regulating the various aspects of cell-intrinsic and cell-extrinsic processes of cancer development. This Review critically discusses the role of adenosine and its receptors in regulating the complex interplay among immune, inflammatory, endothelial and cancer cells during the course of neoplastic disease. PMID- 24226198 TI - Clinical expression and diagnosis of atypical cortical degenerative syndromes. AB - Atypical cortical degenerative syndromes of the non-Alzheimer's disease type are becoming increasingly recognized in the literature. Three cases consisting of primary progressive aphasia, posterior cortical atrophy, and frontal lobe dementia of the non-Alzheimer's type are presented to replicate and extend emerging literature. Detailed clinical description and neuropsychological data, coupled with confirmatory neurofunctional imaging, are presented to provide empirical support that specific inclusion and exclusion criteria can be applied to clinically diagnosis atypical degenerative cortical dementias. PMID- 24226199 TI - The clinical psychologist as program consultant: When is enough enough? AB - One of the most influential roles clinical psychologists play in health care settings is as consultant to medical colleagues. The psychologist consultant typically approaches either clinical or programmatic questions intending to tap both empirical research and clinical judgment perspectives in trying to answer them. This paper describes a specific "program consultation case," a not atypical consultation situation in which graduate medical education directors asked for advice about their residency training program. The purpose is to use this example to generate ideas and provoke discussion about such consultation processes and their usefulness in the health care training and service delivery world. The psychologist may be faced with questions that have meaningful implications beyond the specific consultation. What if the concerns being posed by this particular program are concerns which have been raised before, have been researched before, and have generated reasonable suggestions, conclusions, and strategies for improvement? And what if no one has paid attention, so that the questions are being raised again? When empirical and clinical data consistently combine to identify problems within health-related training or service delivery systems, and when suggestions or alternatives for their solutions have been presented and, also presumably, ignored, what does the clinical psychologist consultant do next? PMID- 24226200 TI - When is enough enough? We are only beginning. AB - Sheridan (1995) presents the problem of the psychologist consulting to a medical residency program as an example of the difficulty one experiences in attempting to challenge, even from a data-based perspective, the calcification inherent in health systems and medical education in particular. This paper responds to her challenging questions, "How much should we get involved in changing health care and medical education, and at what level (local, national) should psychology intervene (if at all)?" It is suggested that psychologists pick up the challenge to bring about change, whenever possible, with the admonition-we are only beginning. PMID- 24226203 TI - Evidence for an alternatively spliced MITF exon 2 variant. PMID- 24226202 TI - The expression of proinflammatory genes in epidermal keratinocytes is regulated by hydration status. AB - Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dressing preserves the hydration of the skin and results in a wound healing phenotype that more closely resembles that of mucosa. Here we explored whether changes in hydration status alter epidermal gene expression patterns in rabbit partial-thickness incisional wounds. Using microarray studies on injured epidermis, we showed that global gene expression patterns in highly occluded versus non-occluded wounds are distinct. Many genes including IL-1beta, IL-8, TNF-alpha (tumor necrosis factor-alpha), and COX-2 (cyclooxygenase 2) are upregulated in non-occluded wounds compared with highly occluded wounds. In addition, decreased levels of hydration resulted in an increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Hierarchical analysis of genes using RNA interference showed that both TNF-alpha and IL-1beta regulate the expression of IL-8 through independent pathways in response to reduced hydration. Furthermore, both gene knockdown and pharmacological inhibition studies showed that COX-2 mediates the TNF-alpha/IL-8 pathway by increasing the production of prostaglandin E2 (PGE2). IL-8 in turn controls the production of matrix metalloproteinase-9 in keratinocytes. Our data show that hydration status directly affects the expression of inflammatory signaling in the epidermis. The identification of genes involved in the epithelial hydration pathway provides an opportunity to develop strategies to reduce scarring and optimize wound healing. PMID- 24226206 TI - Development of an evaluation framework for African-European hospital patient safety partnerships. AB - BACKGROUND: Patient safety is recognised as a significant healthcare problem worldwide, and healthcare-associated infections are an important aspect. African Partnerships for Patient Safety is a WHO programme that pairs hospitals in Africa with hospitals in Europe with the objective to work together to improve patient safety. OBJECTIVE: To describe the development of an evaluation framework for hospital-to-hospital partnerships participating in the programme. METHODS: The framework was structured around the programme's three core objectives: facilitate strong interhospital partnerships, improve in-hospital patient safety and spread best practices nationally. Africa-based clinicians, their European partners and experts in patient safety were closely involved in developing the evaluation framework in an iterative process. RESULTS: The process defined six domains of partnership strength, each with measurable subdomains. We developed a questionnaire to measure these subdomains. Participants selected six indicators of hospital patient safety improvement from a short-list of 22 based on their relevance, sensitivity to intervention and measurement feasibility. Participants proposed 20 measures of spread, which were refined into a two-part conceptual framework, and a data capture tool created. CONCLUSION: Taking a highly participatory approach that closely involved its end users, we developed an evaluation framework and tools to measure partnership strength, patient safety improvements and the spread of best practice. PMID- 24226205 TI - Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer. AB - One way sunlight causes skin cancer is by suppressing anti-tumor immunity. A major mechanism involves altering mast cell migration via the C-X-C motif chemokine receptor 4-C-X-C motif chemokine ligand 12 (CXCR4-CXCL12) chemokine pathway. We have discovered that pharmacologically blocking this pathway with the CXCR4 antagonist AMD3100 prevents both UV radiation-induced immune suppression and skin cancer. The majority of control mice receiving UV-only developed histopathologically confirmed squamous cell carcinomas. In contrast, skin tumor incidence and burden was significantly lower in AMD3100-treated mice. Perhaps most striking was that AMD3100 completely prevented the outgrowth of latent tumors that occurred once UV irradiation ceased. AMD3100 protection from UV immunosuppression and skin cancer was associated with reduced mast cell infiltration into the skin, draining lymph nodes, and the tumor itself. Thus a major target of CXCR4 antagonism was the mast cell. Our results indicate that interfering with UV-induced CXCL12 by antagonizing CXCR4 significantly inhibits skin tumor development by blocking UV-induced effects on mast cells. Hence, the CXCR4-CXCL12 chemokine pathway is a novel therapeutic target in the prevention of UV-induced skin cancer. PMID- 24226208 TI - Reasons for using and failing to use sunscreen: comparison among whites, Hispanics, and Asian/Pacific Islanders in Southern California. PMID- 24226207 TI - The role of technological progress vs. accidental discoveries and clinical experience. AB - The 50th anniversary of dialysotherapy celebrated by nephrologists around the world in 2012 provided an opportunity for discussion on the role of clinical experience in relation to technological progress in the evolution of dialysis, especially of recently observed inadequate decrease in mortality/morbidity rates of patients on chronic dialysis. My report, based on almost 50 years of career in nephrology, refers the evolution of dialysis, from catharsis to modern dialysotherapy with special attention devoted to nowadays gravely underestimated role of clinical experience and personalized professional care for patients. PMID- 24226209 TI - Ionization-induced pi -> H site-switching in phenol-CH4 complexes studied using IR dip spectroscopy. AB - IR spectra of phenol-CH4 complexes generated in a supersonic expansion were measured before and after photoionization. The IR spectrum before ionization shows the free OH stretching vibration (nu(OH)) and the structure of neutral phenol-CH4 in the electronic ground state (S0) is assigned to a pi-bound geometry, in which the CH4 ligand is located above the phenol ring. The IR spectrum after ionization to the cationic ground state (D0) exhibits a red shifted nu(OH) band assigned to a hydrogen-bonded cationic structure, in which the CH4 ligand binds to the phenolic OH group. In contrast to phenol-Ar/Kr, the observed ionization-induced pi -> H migration has unity yield for CH4. This difference is attributed to intracluster vibrational energy redistribution processes. PMID- 24226210 TI - The allotetraploidization of maize : 5. The utilization of zygomeres. AB - Artificial allotetraploidization is the derivation of synthetic allotetraploids. In an allotetraploid, chromosomes of similar genomes pair with their homologues in similar genomes rather than with their homoeologues in the dissimilar genomes. The basis of this discrimination is not completely understood because the mechanisms of chromosome pairing are not adequately known. Sybenga has hypothesized the existence of special units of DNA (zygomeres) that are responsible for the initiation of synapsis of chromosomes during meiosis. Zygomeres, if they exist, should be detectable by preferential pairing studies. In the work reported here, trisome 3 maize plants had two standard chromosomes 3 marked with the genes al sh2 or al Sh2, and an odd chromosome 3 from a commercial inbred line (or derivatives thereof) marked with the dominant alleles A1 Sh2. In a previous study, three inbred lines (B41, Hy, and 38-11) were found to have chromosomes 3 that caused a great amount of preferential pairing. It may be assumed that they have different zygomeres than those of the standard chromosome 3. Hybrids between these inbred lines and hybrids between the inbreds and the standard were used as the donors of the odd chromosome. Segregation for preferential pairing (and presumably for zygomeres) was observed. The data can be explained on the basis of only two zygomeres per chromosome. Zygomeres should be able to be mapped as though they were genes. PMID- 24226211 TI - Genetic variation detected by use of the M13 "DNA fingerprint" probe in Malus, Prunus, and Rubus (Rosaceae). AB - Recently, "DNA fingerprints" have been reported in a wide array of organisms. We used the M13 repeat probe on several genera and species in the angiosperm family Rosaceae. Four apple cultivars could be differentiated when any one of five restriction enzymes was used to analyze minisatellite DNA. Similarly, four individual trees of Prunus serotina (black cherry) exhibited different "fingerprints" with each of four enyzmes. A total of 14 Rubus (blackberries and raspberries) plants representing four species were investigated with two enzymes. Extensive inter-and intraspecific variation was found. However, some closely growing plants had identical "fingerprints", probably due to their being derived through vegetative propagation. PMID- 24226212 TI - Chromosomal location of adenylate kinase isozymes in Triticeae species. AB - One system of monomeric adenylate kinase isozymes, designated ADK, was observed in Triticum aestivum and in five diploid Triticeae species. The gene loci Adk-a, Adk-b and Adk-d were located on 7AL, 7BL and 7DL Triticum aestivum cv "Chinese Spring" chromosomal arms, respectively. Adk gene loci were also located on the 7RL chromosomal arm of Secale cereale cv "Ailes", the 7H chromosome of Hordeum vulgare cv "Betzes", 7X of Agropyron intermedium, 7E of Elytrigia elongata and CSU-E of Aegilops umbellulata. The results suport the notion of the conservation of gene synteny groups within Triticeae species. PMID- 24226213 TI - Germinal reversion of an unstable mutation for anthocyanin pigmentation in soybean. AB - Plants of the "w4-mutable" line of soybean [Glycine max (L.) Merr.] are chimeral for anthocyanin pigmentation. Mutable plants produce both near-white and purple flowers, as well as flowers of mutable phenotype with purple sectors on near white petals. It is established here that the mutable trait is conditioned by an unstable recessive allele of the w4 locus that conditions anthocyanin biosynthesis. The gene symbol w4-m is assigned to the mutable allele. Allele w4-m was derived from a stable, wild-type W4 progenitor allele and reverts at high frequency to a stable, wild-type W4 allele. Reversion occurs both early and late during the development of the germ line. Several experiments give estimates of germinal reversion frequency, indicating that approximately 6% of mutable alleles revert to wild-type from one generation to the next. Allele w4-m exhibits many features typical of an allele controlled by a transposable element. PMID- 24226214 TI - The three C's - competition, coexistence and coevolution - and their impact on the breeding of forage crop mixtures. AB - The role of competition, coexistence and co-evolution in the formation of plant communities is discussed, particularly in relation to the breeding of improved grass/legume mixtures. Competition occurs whenever the demand for a particular resource outstrips supply, with the pressures generated within a species expected to exceed those between species. These pressures must be withstood before populations can coexist within a community. This is accomplished by a process of niche diversification, arising from temporal or spatial differences between the populations, that enables them to draw on resources not readily available to their competitors. Coexistence is crucial to the success of any breeding programme designed to raise the productivity of grass/ legume pastures, because it enables components to adapt not only to the environment which they share, but also to each other. A strategy that improves the "general ecological combining ability" of one or both components by a process of recurrent or reciprocal recurrent unilateral adaptation may prove successful, particularly if existing niche differences are increased thereby. Although both processes may give rise to populations which have apparently coevolved, only those resulting from reciprocal recurrent selection will meet the criteria of specificity and reciprocity. PMID- 24226215 TI - Construction of Beta procumbens-specific DNA probes and their application for the screening of B. vulgaris x B. procumbens (2n = 19) addition lines. AB - Beta procumbens-specific DNA probes have been constructed by cloning digested total DNA in E. coli and screening the resulting recombinant plasmids in dot blot hybridizations with labelled B. procumbens and B. vulgaris DNA. Four clones (pTS1 4) have been analyzed in detail determining their degree of specificity and DNA sequence. Two clones (pTS1 and pTS2) with the highest degree of B. procumbens specificity were adapted for the squash dot hybridization with the aim of screening large numbers of individual hybrid plants (B. vulgaris x B. procumbens) carrying an alien B. procumbens chromosome (2n = 19). These addition lines carry in some cases B. procumbens resistance genes to the beet cyst nematode (Heterodea schachtii Schm.). PMID- 24226216 TI - The assignment of a Thinopyrum distichum (Thunb.) Love-derived translocation to the long arm of wheat chromosome 7D using endopeptidase polymorphisms. AB - Endopeptidase zymograms of the translocation line 'Indis' revealed the presence of several major and minor bands that had differential expression in coleoptile and seed tissues. While 'Indis' lacks Ep-D1a, which is present in the parental cultivar 'Inia 66', it also may not express any of the Th. distichum bands. The 'Indis' zymogram was found to be identical to that of an isogenic line of 'Inia 66' possessing Lr19. Since the absence of an Ep-D1a product appears to be linked to the 7DL translocation, it is possible to use the null condition as a marker for both the Lr19 or 'Indis' translocations. The 'Indis' translocation also did not show recombination with the cn-D1 chlorophyl mutant on 7DL, confirming that a part of 7D was involved. The results of a telocentric mapping experiment involving the 7D telosomes indicated that in 'Indis' a chromosome segment from Th. distichum replaced a large section of 7DL of 'Inia 66'. PMID- 24226217 TI - The development of bridge lines for interspecific gene transfer between Lycopersicon esculentum and L. peruvianum. AB - Using a modified embryo callus culture technique, hybrids between Lycopersicon esculentum and L. peruvianum were developed and their usefulness as bridge lines for facilitating interspecific gene transfer was evaluated. Four of these lines showed a high level of sexual compatibility with several other L. peruvianum var. typicum accessions, as well as with accessions of L. peruvianum var. humifusum and L. peruvianum var. glandulosum and L. esculentum. These bridge line x L. peruvianum hybrids could be crossed with L. esculentum to introgress genes from L. peruvianum into L. esculentum. PMID- 24226218 TI - Molecular analysis of the extent of asymmetry in two asymmetric somatic hybrids of tomato. AB - Two somatic hybrid plants generated from a single fusion event between Lycopersicon esculentum and irradiated L. pennellii protoplasts have been analyzed at the molecular level. Over 30 loci have been analyzed using isozymes and RFLPs. All loci tested on chromosomes 2-10 were heterozygous, while those loci on chromosome 12 were homozygous L. pennellii in both somatic hybrids. In one of the somatic hybrids, 2850, loci on chromosome 1 were also homozygous L. pennellii. The other somatic hybrid, 28F5, was heterozygous at all chromosome 1 loci tested, but exhibited altered stoichiometry of parental bands as compared to the sexual hybrid. Loci on chromosome 2 from both somatic hybrids have altered stoichiometry, with L. pennellii alleles being four times more abundant than expected. Both somatic hybrids contain the L. esculentum chloroplast genome, while only L. pennellii polymorphisms have been detected in the mitochondrial genome. PMID- 24226219 TI - Mapping seed storage protein loci Sec-1 and Sec-3 in relation to five chromosomal rearrangements in rye (Secale cereale L.). AB - Linkage relationships were established between the secalin loci, Sec 1 (40-K gamma and omega secalins, homologous to the wheat gliadins) and Sec 3 (HMW = high molecular-weight secalins, homologous to the wheat HMW glutenin subunits), and five chromosomal rearrangements involving chromosome 1R of rye (Secale cereale L.). These were: interchanges T273W (1RL/5RS), T306W (1RS/5RL), and T850W (1RS/ 4RL), Robertsonian centromere split Rb1RW and the interchanged Robertsonian split Rb2R/248W. The analysis established the linkage relationships between the secalin loci and the breakpoints of the rearrangements, in addition to the quantitative effects of the rearrangements on the linkage. Sec-1 is located in the satellite at a position at least 2.5 cMorgan from the proximal border of the terminal C band, and about 30 cMorgan from the nucleolar organizing region (NOR). The locus is also physically closer to the terminal C-band than to the NOR, but not as much as corresponds with the map distances. Similarly, the physical distance between Sec-3 and the centromere is greater than corresponds with the recombination frequency (0%-9%). Although overall recombination in 1RL remains the same, recombination between the centromere and Sec-3 is greatly reduced in the Robertsonian split combined with the interchange. This is not the case with the single Robertsonian split. PMID- 24226220 TI - Tissue culture isolation of a second mutant locus for increased threonine accumulation in maize. AB - Regenerable maize (Zea mays L.) tissue cultures were selected for ability to grow in the presence of inhibitory (1.0-1.5 mM) concentrations of L-lysine plus L threonine. Testcross kernels from one regenerated plant (LT20) segregated for wild-type and high free threonine concentration in a 1?1 ratio consistent with a single dominant gene for high free threonine. Free threonine concentrations (nmol/mg dry weight) increased an average of 29-fold in bulked F2 kernel samples from heterozygous mutant plants, and the total (free plus protein-bound) threonine concentration increased 68%. Increases in protein-bound methionine, lysine and glycine concentrations were also noted, suggesting a possible effect of the mutation on protein concentration and composition. Allelism tests with a previously selected mutant line, Ltr (*)19, showed that two unlinked, codominant genes conditioned the high free threonine phenotype. Based on a separate study of aspartate kinase feedback inhibition characteristics in the two mutant lines, we propose that the mutant alleles [gene and allele designations are according to guidelines for maize genetic nomenclature (Burnham et al. 1975)] be designated Ask-LT19 and Ask2-LT20 for the Ltr (*)19 and LT20 mutants, respectively. PMID- 24226221 TI - Genetic diversity among Plantagos : 17. A novel trisomic in Plantago lagopus. AB - In the progenies of the crosses between disomics and trisomies, two plants were isolated which carried an extra chromosome that was unlike any in the standard complement. The plants were not alike; while one carried a metacentric, the other had a telocentric extra chromosome. Their detailed structure and possible modes of origin are discussed. PMID- 24226222 TI - Effects of epistasis on tests for linkage in self-pollinated species. AB - Tests for linkage based on covariances among relatives in self-pollinated species are usually based upon an assumption that epistasis is not important. This study was conducted to determine the impact of epistasis on, and to investigate the sensitivity of, such tests. Thirty covariances were calculated for each of ten non-epistatic and ten epistatic genetic models with varying probabilities of recombination between two coupling or repulsion loci. Each set of covariances was tested for linkage by comparing covariances calculated for the model with those expected for an additive-dominance model with no linkage. Results showed that the test for linkage is quite insensitive to the effects of linkage due to the disproportionate influence of inbreeding. Repulsion linkages should be easier to detect than coupling linkages for all models. Epistasis was found to mimic or counteract the effects of linkage. Tests for linkage based on covariances within a hierarchical mating design appear to be insensitive to linkage and may confuse the effects of linkage and epistasis. PMID- 24226223 TI - Multiattribute evaluation of regional cotton variety trials. AB - The Australian Cotton Cultivar Trials (ACCT) are designed to investigate various cotton [Gossypium hirsutum (L.)] lines in several locations in New South Wales and Queensland each year. If these lines are to be assessed by the simultaneous use of yield and lint quality data, then a multivariate technique applicable to three-way data is desirable. Two such techniques, the mixture maximum likelihood method of clustering and three-mode principal component analysis, are described and used to analyze these data. Applied together, the methods enhance each other's usefulness in interpreting the information on the line response patterns across the locations. The methods provide a good integration of the responses across environments of the entries for the different attributes in the trials. For instance, using yield as the sole criterion, the excellence of the namcala and coker group for quality is overlooked. The analyses point to a decision in favor of either high yields of moderate to good quality lint or moderate yield but superior lint quality. The decisions indicated by the methods confirmed the selections made by the plant breeders. The procedures provide a less subjective, relatively easy to apply and interpret analytical method of describing the patterns of performance and associations in complex multiattribute and multilocation trials. This should lead to more efficient selection among lines in such trials. PMID- 24226224 TI - Restriction fragment length polymorphism (RFLP) of wild perennial relatives of soybean. AB - Total DNA from callus tissue of 28 accessions representing seven wild perennial Glycine species was compared using recombinant genomic probes derived from G. max, the soybean. Using two probes, we show that this molecular approach both confirms and extends the model for the taxonomic relationships between the species derived from morphological and cytogenetic data, and that it provides clear evidence that RFLP analysis of genomic sequences has the potential for revealing the derivation of the member species of the wild perennial Glycine taxon. Although, in this preliminary report, the sample size for each species is small, it is clear that the greatest between-accession variation occurs in G. tabacina (B2B2) and G. clandestine (A1A1), suggesting that these may be the taxa from which further speciation occurred in the subgenus. PMID- 24226225 TI - The effect of parental divergence on F2 heterosis in winter wheat crosses. AB - In winter wheat (Triticum aestivum L.), the development of a methodology to estimate genetic divergence between parental lines, when combined with knowledge of parental performance, could be beneficial in the prediction of bulk progeny performance. The objective of this study was to relate F2 heterosis for grain yield and its components in 116 crosses to two independent estimates of genetic divergence among 28 parental genotypes of diverse origins. Genetic divergence between parents was estimated from (a) pedigree relationships (coefficients of kinship) determined without experimentation, and (b) quantitative traits measured in two years of field experimentation in Kansas and North Carolina, USA. These distances, designated (1 -r) and G, respectively, provided ample differentiation among the parents. The 116 F2 bulks were evaluated at four locations in Kansas and North Carolina in one year. Significant rank correlations of 0.46 (P = 0.01) and 0.44 (P = 0.01) were observed between G and grain yield and kernel number heterosis, respectively. Although (1 -r) was poorly associated with grain yield heterosis, G and midparent performance combined to account for 50% of the variation in F2 yields among crosses when (1 -r) was above the median value, whereas they accounted for only 9% of the variation among crosses when (1-r) was below the median. Midparent and (1 -r) had equal effects on F2 grain yield (R (2)= 0.40) when G was greater than the median value. A breeding strategy is proposed whereby parents are first selected on the basis of performance per se and, subsequently, crosses are made between genetically divergent parents that have both large quantitative (G) and pedigree divergence (1 -r). PMID- 24226226 TI - Chloroplast DNA in Pinus monticola : 2. Survey of within-species variability and detection of heteroplasmic individuals. AB - Within-species variability of a restriction site in the chloroplast (cp) DNA in Pinus monticola has been surveyed. Frequencies of two variants of the cp genome are significantly different in interior versus coastal populations. Paternal inheritance of the cp genome predominates, though some individuals have both variants of the genome. The presence of heteroplasmic individuals indicates occasional biparental inheritance. PMID- 24226227 TI - Individual and group selection for productivity in Tribolium castaneum. AB - The usefulness of a non-random group selection method in the improvement of a character influenced by interactions among individuals has been experimentally tested in a population of Tribolium castaneum. The selected trait -number of adults produced in a fixed period of time -showed a clear increase after 11 generations of selection. This increase is related to a reduction in developmental time, and it was specific for the population structure in which selection was applied, vanishing when this structure was altered. PMID- 24226228 TI - Evaluation of selection index: application to the choice of an indirect multitrait selection index for soybean breeding. AB - Selection indices can be used to predict one trait from information available on several traits in order to improve the prediction accuracy. Plant or animal breeders are interested in selecting only the best individuals, and need to compare the efficiency of different trait combinations in order to choose the index ensuring the best prediction quality for individual values. As the usual tools for index evaluation do not remain unbiased in all cases, we propose a robust way of evaluation by means of an estimator of the mean-square error of prediction (EMSEP). This estimator remains valid even when parameters are not known, as usually assumed, but are estimated. EMSEP is applied to the choice of an indirect multitrait selection index at the F5 generation of a classical breeding scheme for soybeans. Best predictions for precocity are obtained by means of indices using only part of the available information. PMID- 24226229 TI - Selection for increased length of reproductive life in mice. AB - An experiment was conducted in mice to examine whether selection can increase reproductive life and lifetime production of progeny. Mice in two lines with litter size standardized at birth and in two lines without standardization were pair-mated at 7 weeks of age and maintained as long as they produced litters up to 382 days. Progeny from the sixth litters were used to maintain the four selected lines, while progeny from the first litters were bred to maintain unselected control lines. Selected and control lines were compared at five and six generations of the selected lines. Contemporary comparisons revealed that the length of reproductive life and most lifetime production traits were significantly greater in the selected than in control lines. Realized heritability of the length of reproductive life ranged from 0.08 to 0.13. It was concluded that the length of reproductive life and lifetime production in mice can be increased by selection. PMID- 24226230 TI - The role of pith, tube, and stalk density in determining sugarcane sucrose content and stalk weight. AB - Selection against pith and tube is one of the major criteria used to eliminate inferior sugarcane (Saccharum spp.) cultivars in early stages of new cultivar evaluation. Understanding the genetic relationships for these traits would facilitate crossing and selection decisions. This study was conducted to determine heritability, genetic coefficient of variation, and the potential for genetic advance by selection for pith, tube, and stalk density. Correlation and path-coefficient analysis studies were conducted to determine the effects of Brix, pith, and stalk density on sucrose content and the effects of stalk volume, tube, and pith on stalk weight. Eighty randomly selected cultivars (four progeny from each of 20 crosses), representing a first clonal stage of a Louisiana sugarcane breeding population, and their parents were planted at St. Gabriel/LA, and yield data were collected in 1986, 1987, and 1988. Pith and tube exhibited large genotype and genotype-by-year variation, whereas variation in stalk density was nonsignificant. Broad-sense and narrow-sense heritabilities were high, moderately high, and low for pith, tube, and stalk density, respectively. Path coefficient analysis revealed that stalk volume was the major factor determining stalk weight. Tube and pith were factors that decreased stalk weight. As expected, Brix was the single most important factor determining sucrose content, however, high stalk density and low pith were also associated with high sucrose content. Sugarcane breeders should practice stringent selection for low pith across years to increase stalk weight and sucrose content. Since stalk density was effectively increased by high sucrose content and low pith, the use of stalk density in breeding and selection should be avoided. The minimal effect of tube on stalk weight suggests that its use as selection criteria be minimized or dropped. PMID- 24226231 TI - The heritability of fitness: some single gene models. AB - Because directional selection exhausts additive-genetic variance, it is frequently claimed that the heritability of fitness should be very close to zero. However, mutation-selection balance generates a certain amount of additive genetic variance, so that even parent-offspring measures of heritability may be greater than zero at equilibrium. Intra-generation heritability may also be non zero, providing the potentials for genetic change following environmental change. PMID- 24226232 TI - Male sterility caused by cytoplasm of Brassica oxyrrhina in B. campestris and B. juncea. AB - Synthetic alloploid Brassica oxyrrhina (2n = 18, OO) x B. campestris (2n = 20, AA) was repeatedly backcrossed with B. campestris to place B. campestris nucleus in the cytoplasm of B. oxyrrhina. Alloplasmic plants, obtained in BC5 generation, were stably male sterile but mildly chlorotic during initial development. Synthetic alloploid B. oxyrrhina-campestris was also hybridized with B. juncea to transfer B. oxyrrhina cytoplasm. Segregation for green and chlorotic plants was observed in BC1 and BC2 generations. By selection, however, normal green male sterile B. juncea was obtained in BC3. Pollen abortion in both B. campestris and B. juncea is post-meiotic. PMID- 24226233 TI - Ion transport by viscous gas flow through capillaries. AB - The effects of a number of experimental parameters on the efficiency of ion transport by viscous gas flow through narrow capillaries have been studied. Both electrospray and corona ion sources were used. The experimental data are consistent with ions loss to the walls of the capillary, which initially is caused mainly by space-charge expansion, but later is caused by diffusion. These processes can result in severe discrimination against low mass ions. The extent of ion loss may be calculated by using a simple model for radial diffusional loss in long cylinders, with an exponential decay of the ion density along the transport capillary. However, such a simple model underestimates ion loss by ignoring the effects of space-charge, turbulent flow, and rapid decay of higher radial diffusion modes (enhanced loss of ions that enter the capillary close to the wall). In contrast, Monte Carlo simulations showed that the effect of the parabolic velocity profile, under laminar flow conditions, is to increase the transmitted ion current, sometimes by several orders of magnitude, relative to the predictions of the simple diffusion model. After considering all these factors, the transmitted current from a corona was well reproduced by using mobility values for ions formed in such discharges. However, the measured transmitted current from an electrospray source was much too high. To explain this, it was necessary to assume that about 2% of the electrospray current is carried by aerosol particles with radii in the 10-25-A range. Finally, it is argued that in glass capillaries wall charging may explain why the transmitted ion current is observed to be very similar to that in metal capillaries. PMID- 24226234 TI - Infrared multiple photon dissociation in the quadrupole ion trap via a multipass optical arrangement. AB - The design of a novel multipass optical arrangement for use with infrared multiple photon dissociation (IRMPD) in the quadrupole ion trap is presented. This design circumvents previous problems of limited IR laser power, small IR absorption cross sections for many molecules, and the limited ion statistics of trapping and detection of ions for IRMPD in the quadrupole ion trap. In contrast to previous designs that utilized the quadrupole ion store, the quadrupole ion trap was operated in the mass selective instability mode with concurrent resonance ejection. The instrumental design consisted of a modified ring electrode with three spherical concave mirrors mounted on the inner surface of the ring. This modified design allowed for eight laser passes across the radial plane of the ring electrode. IRMPD of protonated bis(2-methoxyethyl)ether (diglyme) was used to characterize the performance of the multipass ring electrode. Two consecutive reactions for the IRMPD of protonated diglyme were observed with a lower energy channel predominant at less than 0.6 J (irradiation times from 1 to 30 ms) and a second channel predominant at energies greater than 0.6 J (irradiation times > 30 ms). Other studies presented include a discussion of the dissociation kinetics of protonated diglyme, the use of a pulsed valve for increased trapping efficiency of parent ion populations, and the effects of laser wavelength and of ion residence time in the radial plane of the ring electrode on photodissociation efficiency. PMID- 24226235 TI - Capillary electrophoresis fourier transform ion cyclotron resonance mass spectrometry with sustained off-resonance irradiation for the characterization of protein and peptide mixtures. AB - A new approach to protein and peptide analysis that involves the coupling of on line capillary electrophoresis-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry with a variation of sustained off-resonance irradiation is described. With this technique, multiple irradiation frequencies are broadcast simultaneously, which yields fragmentation of species at different mass-to-charge ratio values from the same waveform. In conjunction with capillary electrophoresis, this technique can provide sequence information from small amounts of proteins or peptides in complex mixtures. Initial results obtained from a mixture of gramicidin S (1141 u), bee venom melittin (2845 u), and equine apomyoglobin (16,951 u) are presented. PMID- 24226236 TI - Selective parent ion axialization for improved efficiency of collision-induced dissociation in laser desorption-ionization fourier transform ion cyclotron resonance mass spectrometry. AB - We have systematically established the excitation frequency, amplitude, duration, and buffer gas pressure for optimal axialization efficiency and mass selectivity of quadrupolar excitation-collisional cooling for isolation of parent ions for collision-induced dissociation in Fourier transform ion cyclotron resonance mass spectrometry. For example, at high quadrupolar excitation amplitude, ion axialization efficiency and selectivity are optimal when the applied quadrupolar excitation frequency is lower than the unperturbed ion cyclotron frequency by up to several hundred hertz. Moreover, at high buffer gas pressure (10(-6) Torr), quadrupolar excitation duration can be quite short because of efficient collisional cooling of the cyclotron motion produced by magnetron-to-cyclotron conversion. Efficiency, detected signal magnitude, and mass resolving power for collision-induced dissociation (CID) product ions are significantly enhanced by prior parent ion axialization. With this method, we use argon CID to show that C 94 (+) (m/z 1128) formed by Nd:YAG laser desorption-ionization behaves as a closed-cage structure. PMID- 24226237 TI - Investigation of the effect of a dc glow discharge on the performance of a particle beam liquid chromatography/mass spectrometry interface. AB - A low voltage (180-V) dc glow discharge device was inserted just below the pneumatic nebulizer in a particle beam interface of a high performance liquid chromatography/mass spectrometry system. The discharge in a helium atmosphere increased the signal produced by 12 test compounds by factors of about 2-6. The increases in signal were probably produced by an increase in the efficiency of solute transmission through the interface. The signal increases caused by the glow discharge were compared to somewhat larger increases caused by 0.01-M ammonium acetate in the mobile phase. The combination of glow discharge and ammonium acetate provided no meaningful advantage over the individual techniques. The mechanism of improved transport efficiency is not proven, but the neutralization of charged particles is a viable hypothesis. PMID- 24226239 TI - A tandem mass spectrometry study of the gas phase RSC6H 5Cr (+)L (R = H, C 6H 5; L = arene) and C 6H 5SSC 6H 5Cr (+) ions. AB - Ion-molecule reactions of chromium containing ions with arylsulfides have been studied in the gas phase and their products have been characterized by tandem mass spectrometry. C6H5SH and (C6H5)2S react as typical aromatic compounds and give rise to Cr(+)C6H5SR] and RC6H5Cr(+)QH5SR' [R = H, CH3, CH(CH3)2; R' = H, C6H5] ions. Metastable ion mass spectra of the latter species show that the metal is more strongly bound to diphenylsulfide than to alkylbenzenes. C6H5SSC6H5 reacts with chromium-containing ions to form only Cr(+)(C6H5SSC6H5). The decomposition characteristics of this ion and, in particular, the presence of a recovery signal in the neutralization-reionization mass spectrum are in keeping with the formation of a 1,2-dithia[2]cyclophane complex ion, which rearranges into a structurel(s) that contains Cr-S bond(s). No evidence was found for metal atom insertion into S-S, C-S, or S-H bonds. PMID- 24226238 TI - Ion formation of N-Methyl carbamate pesticides in thermospray mass spectrometry: The effects of additives to the liquid chromatographic eluent and of the vaporizer temperature. AB - The effects of three additives-ammonium acetate, ammonium formate, and nicotinic acid-to the liquid chromatographic (LC) eluent and of the vaporizer temperature on the ion formation of N-methyl carbamate pesticides in thermospray (TSP) mass spectrometry was investigated by using filament- or discharge-assisted ionization. Nineteen carbamates and 12 of their known environmental degradation products were used as model compounds. The additives cause a strong reduction in the abundance of the characteristic fragment ions [M + H - CH3NCO](+) and [M - H CH3NCO](-) for some of the carbamates. The addition of nicotinic acid reduces the quasimolecular ion intensity and, in most cases, produces nicotinic acid adduct ions. The addition of ammonium acetate or ammonium formate increases the intensity of the quasimolecular ion and in most cases produces a base peak for the ammonium adduct ion. The combination of a suppression of fragmentation and an enhancement of quasimolecular ion formation produces an overall gain in sensitivity. As to more specific effects, the addition of the ammonium salts reduces the intensity of M(-*) with the chlorinated carbamate barban and suppresses the formation of "odd" adduct ions in the TSP mass spectra of most other carbamates. Monitoring the intensity of the fragment and the quasimolecular ion signal as a function of the probe stem temperature, and the related probe tip temperature, proved to be an easy method to study the thermal degradation of the carbamates. This monitoring procedure showed that methiocarb and its sulfone already suffer from thermal degradation at a stem temperature of 90 degrees C and that these compounds will therefore present problems in quantitation with LC/TSP mass spectrometry. PMID- 24226240 TI - N-Alkylnicotinium halides: A class of cationic matrix additives for enhancing the sensitivity in negative ion Fast-Atom bombardment mass spectrometry of polyanionic analytes. AB - The addition of some surfactants to the fast-atom bombardment (FAB) matrix previously has been demonstrated to enhance analyte signals in fast-atom bombardment mass spectrometry. In particular, cationic surfactants appear to enhance the negative ion FAB detectability of analytes that exist as anionic species in the matrix solution. It has been proposed that the charged surfactant concentrates the oppositely charged analyte near the surface, which results in larger signals for the analyte. Cationic surfactants that contain a fixed positive charge and an additional basic site were prepared with different hydrophobic moieties and were evaluated for their effectiveness as FAB matrix additives. The compound N-octylnico-tinium bromide (ONBr) is shown to improve greatly the analyte-related signals in negative ion fast-atom bombardment mass spectrometry for a variety of polyanionic analytes, relative to other surfactants (e.g., cetylpyridinium salts). This surfactant not only enhances detectability, but also simplifies the pseudomolecular ion region of the resulting spectra by reducing or eliminating metal cation adduct peaks. The simple mechanism of enhancement via surface activity is evaluated, and alternative mechanisms are considered. It is clearly shown that ONBr, as a FAB matrix additive, will allow mass spectrometry to be used for the analysis of anionic compounds that normally exhibit very low responses. PMID- 24226242 TI - Involvement of strictosidine as a defensive chemical inCatharanthus roseus. AB - The involvement of the glucoalkaloid strictosidine in antimicrobial and antifeedant activity inCatharanthus roseus leaves was investigated. Strictosidine and its deglucosylation product, specifically formed by the enzyme strictosidine glucosidase, were shown to be active against several microorganisms. In contrast, neither the intact glucoside, nor the aglycone product(s) was found to exhibit antifeedant activity againstSpodoptera exigua larvae, as was found for intactC. roseus leaves and leaf extracts. Besides alkaloids further downstream in the biosynthesis pathway, a more apolar, yet unidentified compound may be involved in this activity. PMID- 24226243 TI - Combined chemical defenses against an insect-fungal complex. AB - This study considered how host plant allelochemicals may contribute to defense against insects and fungi that jointly colonize the subcortical tissues of trees, the relative roles of constitutive and inducible chemistry in these defenses, and how the actions of two different feeding guilds might be interrelated. Our model consisted of the coniferous treePinus resinosa, the root- and lower stem colonizing beetlesHylastes porculus andDendroctonus valens, and their associated fungiLeptographium procerum andL. terebrantis, and the stem-colonizing bark beetleIps pini and its associated fungusOphiostoma ips. In a novel bioassay, extracts from reaction tissue elicted by wound inoculation withL. terebrantis were more repellent to beetles than were similar extracts from constitutive or mechanically wounded tissue. The effect on beetle behavior was more pronounced in nonpolar extracts, which contain mostly monoterpenes, than in polar extracts, which contain mostly phenolics. Synthetic monoterpenes at concentrations present in the various tissues exerted similar effects and were likewise repellent in dose-response experiments. Growth ofL. procerum andL. terebrantis was inhibited by polar extracts from constitutive and reaction tissue. Inhibition was higher in wounded than control tissue, but the inhibition response did not vary with the type of wounding. Synthetic monoterpenes strongly inhibited spore germination and mycelial growth of both fungi. Colonization of red pine roots byLeptographium spp. altered the subsequent effects of extracts of stem phloem tissue onI. pini. These effects varied with host condition. Beetles preferred extracts from constitutive stem phloem tissue of healthy trees to that of root-diseased trees. However, extracts from reaction tissues of healthy trees were more repellent toI. pini than were the reaction tissues of root-diseased trees. The implications of these results to plant defense against insect-fungal complexes and interactions among different feeding guilds are discussed. PMID- 24226244 TI - Optimization of semiochemical-based trapping ofMetamasius hemipterus sericeus (Olivier) (Coleoptera: Curculionidae). AB - Response of adults of the West Indian sugarcane weevil,Metamasius hemipterus sericeus, to various semiochemical treatments and physical trap designs was studied in southern Florida in field-grown banana and Canary Island date palms. Ethyl acetate released alone at 860-1007 mg/day was as effective for the capture ofM. h. sericeus as a combination of ethyl acetate (844-919 mg/day), ethyl propionate (348-362 mg/day), and ethyl butyrate (117-137 mg/day) and in one trial was more effective than fermenting sugarcane (250 g), ethyl propionate alone (353 384 mg/day), ethyl butyrate alone (123-174 mg/day), or no treatment. Ethyl acetate released alone at 675-683 mg/day was as attractive as 250 g of fermenting sugarcane or the racemic blend of the male-produced aggregation pheromones [(+/-) 5-methyl-nonan-4-ol and (+/-)-2-methyl-heptan-4-ol (8:1 ratio) "metalure"] at 3 mg/day. Weevil counts increased with binary combinations of ethyl acetate, sugarcane, and/or metalure over these treatments alone and the ternary combination was two to three times more effective than any of the binary treatments. Attraction to ethyl acetate released alone at 777 mg/day with metalure was greater than to the hydrolysis products of ethyl acetate (ethanol and/or acetic acid each released at about 6-8 mg/day) with metalure. Weevil counts from traps baited with 250 g of sugarcane and metalure increased with increasing dose of ethyl acetate to about 400 mg/day and then appeared to plateau. Ethyl acetate (about 700 mg/day) and metalure increased weevil counts in traps with increasing amounts of sugarcane (0-2 kg). Molasses (45 g) + water (158 ml) substitutes for sugarcane were about as effective for capturingM. h. sericeus as 250 g of fermenting sugarcane [all treatments with ethyl acetate (847 mg/day) and metalure]. Early experiments used a lethal pitfall trap. We demonstrated that several alternative trap designs were more effective than the lethal pitfall trap for capturing weevils. Color and height (on ground vs. 1 m on pole) did not affect trap efficacy when baited with the ternary combination of ethyl acetate (672-825 mg/day), sugarcane (250 g), and metalure. PMID- 24226245 TI - Lipid compounds in secretions of fishing bat,Noctilio leporinus (Chiroptera: Noctilionidae). AB - The distinctive odor ofNoctilio leporinus arises from oily secretions found beneath the wings in the subaxillary region. Analysis of secretions by gas chromatography-mass spectrometry identified 372 lipid compounds. Differences in number and chemical composition of glycolipids suggest that secretions of males from the same roost are more similar to each other than to other males or females. Differences in number and chemical composition of nonpolar lipids indicate that secretions of males are more similar to each other than to females. Since secretions differ between sexes, information on sexual identity and reproductive condition may be communicated. Individually unique lipid compositions further suggest that bats may be recognizable by their odor within the roost and while flying. PMID- 24226246 TI - Attractant pheromone for male rice bug,Leptocorisa chinensis: Semiochemicals produced by both male and female. AB - GC profiles of the airborne volatiles produced by adult males and females of the rice bug,L. chinensis showed no qualitative chemical dimorphism. However, GC-EAD experiments showed that eight of the compounds elicited strong responses in male and female antennae. Ruling out alarm pheromone and compounds that were not found in the whole-body extracts of the bugs, four compounds remained to be tested as possible attractants. In field experiments, the whole mixture or tertiary blends were not attractive: however, males were strongly attracted to a 5 : 1 mixture of 2-(E)-octenyl acetate and octanol. The attractancy of the binary mixture was decreased by the addition of 3-(Z)-octenyl actetate. Although the binary lure specifically attracted males, there was no evidence that it triggered any response of sexual behavior in males. PMID- 24226247 TI - Interspecific advantage results in intraspecific disadvantage: Chemical protection versus cannibalism inUtetheisa ornatrix (Lepidoptera: Arctiidae). AB - This study suggests that alkaloid deficiency inUtetheisa (Lepidoptera: Arctiidae) is a main cause of cannibalism; moreover, cannibalism can be predicted on the basis of alkaloid deficiency and of systemic alkaloid accumulation. This chemical plays a central role in the life of this species, because, first, it provides acquired chemical protection from potential predators, and, second, it determines mating success (as the alkaloid is an essential precursor of the male pheromone). Consequently, losers in the larval sequestering of alkaloids, which would result in a lack of chemical protection and in decreased mating success, tend to target conspecific winners, which are normally substantially protected against a variety of predators; by cannibalizing those accumulated alkaloid sources the losers tend to become the winners of cannibalistic encounters while making up their shortfall of these chemicals. What is a presumptive advantage in selection under high predation pressures and/or high alkaloid availabilities could become a disadvantage under high conspecific population densities and shortages of alkaloid supplies for larval uptake. Cannibalism may be expected to have general ecological importance in the evolutionary play ofUtetheisa and may contribute to a balanced regulation of the acquired alkaloid contents in these arctiid populations. PMID- 24226248 TI - Insect antifeedant and growth-regulating activities of Salannin and other c-seco limonoids from neem oil in relation to Azadirachtin. AB - The antifeedant and insect growth-regulating activities of salannin, nimbin, and 6-deacetylnimbin, in comparison with azadirachtin-A, have been studied againstSpodoptera litura, Pericallia ricini, andOxya fuscovittata. Salannin deterred feeding, delayed molt by increasing larval duration, caused larval and pupal mortalities, and decreased pupal weights in the two lepidopterans. Salannin also caused molt delays and nymphal mortalities inOxya fuscovittata. The role of salannin and other compounds in conferring bioactivity, along with azadirachtin A, to neem oil/neem seed extracts is emphasized. PMID- 24226249 TI - Threshold chemosensitivity and hypothetical chemoreceptor function of the nematodeCaenorhabditis elegans. AB - The behavioral responses by the nematodeCaenorhabditis elegans to 12 organic compounds was explored using tethered nematode and computer tracking methods. Results indicate that the nematode is attracted to acetone, diethyl ether, isoamyl acetate, isoamyl alcohol, 2,4-pentanedione, andn-propanol. No responses were detected to acetaldehyde, acetylcholine, ethanol, formaldehyde, i-propanol, and valerate. Isoamyl acetate and acetone were found to be the most potent attractants eliciting minimal responses at concentrations near 10(-10) M. The geometry and charge distribution of a single hypothetical receptor that would interact with all the compounds that elicited a response and none of the compounds that failed to elicit a response is explored. PMID- 24226250 TI - 9-Methylgermacrene-B; proposed structure for novel homosesquiterpene from the sex pheromone glands ofLutzomyia longipalpis (Diptera: Psychodidae) from Lapinha, Brazil. AB - The principal volatile component (99 + %) of the sex pheromone glands ofLutzomyia longipalpis from Lapinha, Brazil, has been isolated and characterized as a novel homosesquiterpene with the specific structure proposed as 9-methylgermacrene-B, (E,E)-8-(1-methylethylidenyl)-1,5,10-trimethyl-1,5-cyclodecadiene. PMID- 24226251 TI - Effect of simple phenolic compounds of heather (Calluna vulgaris) on rumen microbial activity in vitro. AB - Heather (Calluna vulgaris), a common dietary component of many mammalian herbivores, contains a broad range of tannin phenolics, flavonoids, and simple phenolic compounds. These may lead to a number of negative effects on herbivores as a result of toxicity or digestive inhibition. We assessed the effect of some simple phenolic compounds from heather on rumen microbial activity using thein vitro consecutive batch culture technique. The compounds tested were orcinol, quinol, and arbutin, a glucoside of quinol. At a concentration of 10 mM, both orcinol and quinol depressed production of gas and volatile fatty acids (VFAs). Orcinol and, to a lesser extent, quinol also reduced digestion of the substrate. In contrast to these negative effects on rumen microbial fermentation, arbutin stimulated both gas and VFA production, probably due to the presence of the fermentable sugar moiety. The presence of arbutin also resulted in different concentrations and proportions of VFAs compared to the presence of orcinol and quinol. Since many simple phenolic compounds are found in plants in the form of glycosides, the negative digestive effects of the phenolic moieties may be accompanied by the positive effect of the sugar moiety, which is liberated in the gastrointestinal tract on hydrolysis by glycosidase enzymes. This study suggests that when phenolics are present as glycosides, they do not necessarily adversely affect digestion by herbivores. PMID- 24226252 TI - Olefinic acetates, Delta-9,11-14: OAc and Delta-7,9-12: OAc used as sex pheromone components in three geometrid moths,Idaea aversata, I. straminata, andI. biselata (Geometridae, Lepidoptera). AB - Pheromone compounds so far identified from most geometrid moths consist of all-Z diene, triene, or tetraene hydrocarbons with chain lengths of C17 to C21, and their monoepoxide derivatives biosynthesized from linoleic and linolenic acids. The present study reports the occurrence of olefinic acetates as sex pheromones in three species of Geometridae. (Z,Z)-9,11-tetradecadienyl acetate and (Z,Z)-7,9 dodecadienyl acetate found in female gland extracts ofIdaea aversata elicited significant responses from conspecific male antennae in gas chromatography with electroantennographic detection (GCEAD). In extracts ofI. straminata, (Z,Z)-7,9 dodecadienyl acetate, (E,Z)-7,9-dodecadienyl acetate, and (Z,Z)-7,9-dodecadienyl acetate were found, and the synthetic compounds elicited strong responses from conspecific male antennae. In the third species,I. biselata, only (Z,Z)-7,9 dodecadienyl acetate was found in the female extracts, and this compound elicited a strong EAD response from the conspecific male antenna. The identities of the pheromone components inI. aversata andI. straminata were further confirmed according to their characteristic ions after GC-MS analyses. Single sensillum recordings fromI. aversata showed two types of pheromone-detecting sensilla present on the male antenna. One type contained two receptor neurons, one of which was specifically tuned to (Z,Z)-9,11-tetradecadienyl acetate, the other to (Z,E)-9,11-tetradecadienyl acetate. A second type contained one neuron responding to (Z,Z)-7,9-dodecadienyl acetate. The two types were clearly different also with respect to external morphology, the former being considerably longer and having a larger base diameter. Also inI. straminata two physiological types of sensilla could be distinguished. One type contained two neurons, one of which responded to (Z,Z)-7,9-dodecadienyl acetate, the other to (Z,E)-9,11-tetradecadienyl acetate. The second type contained one neuron, responding to (Z,Z)-7,9-dodecadienyl acetate. No correlation between external morphology and physiological response of the investigated sensilla was observed inI. straminata. In field tests, a two component blend containing (Z,Z)-9,11-tetradecadienyl acetate and (Z,Z)-7,9 dodecadienyl acetate in a ratio of 10:1 was attractive to males ofI. aversata. This two-component blend was also attractive to males ofI. straminata, but in a ratio of 1:1. High numbers of maleI. biselata were caught in traps baited with (Z,Z)-7,9-dodecadienyl acetate alone. The incorporation of deuterium labels into pheromone components after topical application of deuterium-labeled palmitic acid confirmed that the pheromone components ofI. aversata could be synthesized from this precursor, as has been previously observed for acetate pheromone components of many other moth species. Our results suggest that an evolutionary reversal back to the production of palmitic acid-derived pheromone components has occurred within the geometrid subfamily Sterrhinae. PMID- 24226253 TI - The importance of sequestered iridoid glycosides as a defense against an ant predator. AB - We reared larvae ofJunonia coenia Hubner (Nymphalidae) on artificial diets with trace concentrations of iridoid glycosides and on leaf diets with higher concentrations of iridoid glycosides. We offered these caterpillars to predacious ants and observed the effects of the following on predation: diet (artificial vs. leaf), site (ant colonies in dry vs. wet areas), instar (early vs. late), and time (changes in predation over five days). Diet and site were consistently significant predictors of the ants' propensities to reject prey and the caterpillars' abilities to escape predation. Leaf-diet caterpillars escaped more frequently than artificial-diet caterpillars, and ants from dry sites were more likely to reject prey than ants from wet sites. The percentage of iridoid glycosides found in individual caterpillars was also a good predictor of the probability of rejection by predators and prey escape. Caterpillars with higher levels of iridoids were more likely to be rejected and to escape, suggesting that sequestered iridoid glycosides are a defense against predaceous ants. PMID- 24226254 TI - Mass-trapping ofCarpophilus spp. (Coleoptera: Nitidulidae) in stone fruit orchards using synthetic aggregation pheromones and a coattractant: Development of a strategy for population suppression. AB - Experiments were conducted in southern New South Wales to evaluate the potential of mass-trapping using synthetic aggregation pheromones and a coattractant as a control option forCarpophilus spp. in stone fruit orchards. A cordon of 54 pipe and 54 funnel traps (one trap of each type per perimeter tree) baited with pheromones ofC. mutilatus andC. davidsoni and coattractant (fermenting bread dough) was maintained around an apricot orchard for three weeks prior to harvest. The incidence ofCarpophilus spp. in ripe fruit in the center of the orchard was significantly reduced compared to a nearby orchard or the perimeter trees containing traps. A cordon of 16 water-filled Magnet funnel traps baited with pheromones ofC. mutilatus andC. davidsoni and coattractant was placed around a 9 * 9 block of trees in a peach orchard (single traps on alternate perimeter trees). This trapping regime significantly reduced infestation of fruit baits byCarpophilus spp. in the center tree over a period of six weeks compared to fruit baits in trap trees and distant (100 m) control trees. However, cordons of eight pheromone traps within 1 m of single trees or a single trap adjacent to a tree increasedCarpophilus spp. infestation of fruit baits by up to 7.5 * compared to trees without pheromone traps. Mass-trapping based on perimeter positioning of pheromone traps (at a yet to be determined distance from protected trees) appears to show potential as a control strategy forCarpophilus spp. in stone fruit orchards during fruit ripening and harvest but traps too close to trees must be avoided. Development of a strategy for population suppression is discussed with respect to trap type, efficacy, positioning, and density; pheromone and coattractant delivery systems; and orchard sanitation. PMID- 24226255 TI - Aggregation of the scarab beetleHolotrichia consanguinea in response to female released pheromone suggests secondary function hypothesis for semiochemical. AB - The pheromone system of the scarab beetleH. consanguinea, an agricultural pest native to India, was investigated by extracting abdominal glands of females with dichloromethane and ether and analyzing them by GC-MS. Indoor bioassays with the natural product separated on a silica gel column showed that males responded to the hexane-ether (80:20) fraction by displaying a clear sexual behavior. Although the indoor bioassay-oriented approach did not lead to the identification of the active compound(s), field tests of candidate chemicals-anisole, indole, and phenol-showed that beetles responded strongly to anisole. Males and females were captured in anisolebaited traps in a ratio close to 1:1. Nearly the same sex ratio was also observed in beetles captured over the time during the flight activity of the beetles in the field. Because no clear evolutionary basis exists for why competing females are attracted to the semiochemical, it was simply referred to as a "female-released pheromone." PMID- 24226256 TI - Structure-activity relationships in glucosinolates and other compounds stimulating oviposition in the cabbage root fly (Delia radicum). AB - The ability of a range of glucosinolates and other compounds in stimulating oviposition of the cabbage root fly (Delia radicum) was determined using a bioassay based on the use of surrogate leaves coated with test compounds. The results show that chemically dissimilar compounds are effective stimulants providing they contain the S=O group. No other part of the glucosinolate molecule was shown to be necessary. It has been shown that compounds other than glucosinolates may be important in the oviposition behavior ofD. radicum. PMID- 24226257 TI - Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE). AB - There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis. PMID- 24226258 TI - Does oral 3,5,3 '-triiodo-l-thyronine affect dietary glucose utilization and plasma insulin levels in rainbow trout (Salmo gairdneri)? AB - A factorial experiment was conducted to determine the effect and interaction of dietary carbohydrate level and triiodo-L-thyronine (T3) supplementation on the growth, physiological response and plasma insulin and cortisol levels of rainbow trout. The oral administration of T3 significantly increased the growth, protein efficiency ratio and feed efficiency of trout, indicating an increased protein and perhaps energy utilization in these fish. However, T, administration did not significantly increase the utilization of dietary glucose as an energy source by the trout. Similarly, the administration of T3 did not significantly affect plasma insulin levels in either the fed or the fasted trout. Plasma insulin levels were significantly higher in fed trout reared on the non-T3 supplemented high carbohydrate diet in comparison to trout reared on the low carbohydrate diets. This indicates that increased dietary carbohydrate stimulates increased insulin secretion in the trout. Therefore, although rainbow trout are not insulin deficient, they can still be considered a diabetic-like animal due to their poor glucose tolerance. Plasma cortisol levels were not affected by diet composition and altered plasma glucose levels. PMID- 24226259 TI - Effects of triiodothyronine and propylthiouracil on thyroid function and smoltification of coho salmon (Oncorhynchus kisutch). AB - Yearling coho salmon (Oncorhynchus kisutch) were fed diets containing triiodothyronine (T3; 4 or 12gmg), propylthiouracil (PTU; 1.5 or 6.0 mg/g), or both T3 (12MUg/g) and PTU (1.5 mg/g) from January 10 to May 29. Plasma T4 and T3, concentrations were maintained within normal physiological limits in all groups of treated fish. Increases in plasma thyroxine (T4) occurred in late April in groups receiving the high dose of T3 or PTU, or the combination of T3, and PTU. Peaks of plasma T4 occurred in May in the other groups. Thyroid follicle epithelial cell height was increased in the groups in the following order: highest; PTU (6.0 mg/g), PTU (1.5 mg/g), PTU + T3, control, T3 (4gmg/g), T3 (12MUg/g); lowest. In March specific binding of T3 by liver nuclei was not affected by treatment with T3 (12MUg/g) but was decreased 30% by treatment with PTU (6.0MUg/g). Body growth, food conversion efficiency, and pigmentary changes were increased by T3 (12MUg/g), decreased dose-dependently by PTU, and unaffected by the other dietary treatments. All treatments altered body proximate composition. Food consumption and the ability to osmoregulate in seawater were decreased in fish fed 6.0 mg/g PTU, but were unaffected by the other dietary treatments. These results suggest that during smoltification: 1) Thyroid hormones may be involved in control of thyroidal function and body growth and pigmentary changes, 2) Hypo-osmoregulatory competence is not further stimulated by exogenous T3 and 3) PTU does not block T4 synthesis but may block T3, action by interfering with nuclear T3 binding. PMID- 24226260 TI - Annual cycle of plasma insulin and glucose of sea bass.Dicentrarchus labrax, L. AB - Annual plasma insulin and glucose cycles were studied inDicentrarchus labrax maintained in either seawater (37.80/00) or brackish water (3.50/00). In both media, the highest insulin levels were found during the prespawning period (August-November) coincident to increases in weight and a decrease in plasma glucose. During spawning (December-April) and postspawning (May-July) periods, the decrease in insulin occurred at the same time as a reduction in growth and an increase of plasma glucose. Temperature and salinity conditions impeded spawning in the brackish water group, in which a minor weight loss was regained more quickly than in the sea water group; insulin levels were also higher. PMID- 24226261 TI - Control of gallbladder motility in the rainbow trout,Salmo gairdneri. AB - Immunohistochemistry revealed nerves containing VIP-like and 5-HT-like material in both gallbladder wall and bile duct of the rainbow trout, while endocrine cells containing gastrin/CCK-like and substance P-like material were present in the mucosa of the bile duct and the duodenum. Fluorescence histochemistry showed adrenergic nerves close to the muscle layer of the gallbladder.Sulphated CCK8, caerulein and non-sulphated CCK8 (in this order of potency), 5-HT and acetylcholine were excitatory on isolated strip preparations, while VIP and adrenergic agonists were inhibitory. The adrenergic drugs were probably actingvia a beta-adrenergic receptor, while the effects of 5-HT and cholinergic drugs were antagonized by methysergide and atropine respectively.Electrical stimulation of the gallbladder nervesin situ failed to show any effect or under certain conditions induced a rebound effect.It is concluded that the motility control of the rainbow trout gallbladder may involve an inhibitory innervation by adrenergic and possibly VIP-releasing nerves, while 5-HT, acetylcholine and a CCK-like substance may be involved in the excitatory control. PMID- 24226262 TI - Physiological responses to continuous swimming in wild salmon (Salmo salar L.) parr and smolt. AB - Wild salmon (Salmo salar) parr and smolt were forced to swim against constant flow (50 cm.s(-1)) for 8 hours. Physiological properties describing the hormonal status, the energy metabolism and the ionic and osmotic balance of fish were measured from the fish prior to and at the end of the swimming test.Plasma cortisol levels were elevated in response to enforced swimming; the response of the smolt was clearly greater than that of the parr. Plasma thyroxine concentration increased in the parr but stayed at the initial level in the smolts. The parr consumed much of their coelomic fat, but the glycogen stores stayed nearly constant. The smolts had very low fat stores, and the glycogen stores were depleted in the test. The ionic and osmotic balance of the parr was stable in the test, but in smolts, the plasma Cl(-1) and osmotic concentrations decreased and muscle moisture increased.The results indicate that downstream migration smolts have markedly lower physiological capacity for continuous swimming than parr. PMID- 24226263 TI - The regulation of reactive changes around multiple sclerosis lesions by phosphorylated signal transducer and activator of transcription. AB - Activation of signal transducer and activator of transcription 3 (STAT3) by phosphorylation is thought to mediate anti-inflammatory responses to CNS injury. Several studies have reported an increase in phosphorylated STAT3 (pSTAT3) in peripheral T cells and monocytes from patients with multiple sclerosis (MS) during relapses, suggesting that pSTAT3 might represent an inflammatory marker. Here, we examined immunoreactivity for pSTAT3 in brain tissue samples from MS patients and controls. Phosphorylated STAT3 immunoreactivity was sparse within lesions, with no difference between active and inactive lesions. It was, however, significantly greater in white matter (WM) adjacent to active and inactive lesions; moreover, it was significantly greater in WM adjacent to active versus inactive lesions. Phosphorylated STAT3-positive cells were identified as astrocytes and macrophages/microglia. Phosphorylated STAT3 expression was also detected by Western blotting in WM of patients with MS. In comparison, pSTAT3 immunoreactivity was either rare or found focally in brain tissue samples from patients with other neurologic diseases. Our findings show that pSTAT3 does not correlate with inflammatory activity in MS lesions, but that it may play an important role in regulating reactive changes proximal to MS lesions. PMID- 24226264 TI - Thiamine deficiency induces massive cell death in the olfactory bulbs of mice. AB - Thiamine (vitamin B1) deficiency (TD) leads to focal brain necrosis in particular brain regions in humans and in experimental animal models. The precise mechanism of the selective topographic vulnerability triggered by TD still remains unclear. We examined the distribution pattern of cell death in the brains of mice in an experimental model of TD using anti-single-strand DNA immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling methods. We found that interneurons in the olfactory bulb were sensitive to TD. The morphologic aspects of cell death in the olfactory bulb resembled those of cell death in thalamic neurons, which have previously been examined in detail. Furthermore, cell death in the olfactory bulb was partly relieved by the administration of an N-methyl-d-aspartate receptor antagonist, as was the case in thalamic lesions by TD. The superficial part of the olfactory granule cell layer seemed to be the most sensitive to TD, suggesting that differences in the afferents between superficial and deep granule cells may influence the sensitivity of these cells to TD. Our results indicate that the olfactory bulb should be considered as one of the vulnerable regions to TD. PMID- 24226265 TI - Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients. AB - There is a cholinergic deficit in Parkinson disease (PD) and in dementia with Lewy bodies (DLB) that plays a role in a variety of clinical symptoms, including visual hallucinations (VH). The aim of this study was to assess cholinergic neuronal loss and PD and Alzheimer disease pathology in the pedunculopontine nucleus pars compacta (PPNc) of PD and DLB patients with VH. Postmortem brainstem tissue samples of 9 clinically diagnosed and pathologically confirmed PD patients with VH, 9 DLB patients with VH, and 9 age- and sex-matched nondemented controls were obtained from the Netherlands Brain Bank. Using a morphometric approach, we estimated the density of cholinergic neurons in the PPNc and determined the local load of alpha-synuclein-immunoreactive Lewy pathology, neurofibrillary tangles, and beta-amyloid plaques. Cholinergic cell density in the PPNc was significantly lower in PD compared with DLB patients with VH (-39%, p < 0.001) and controls ( 41%, p < 0.001). Alpha-synuclein load was higher in PD, whereas beta-amyloid plaque pathology was more pronounced in DLB patients. The mean cell density in DLB patients was not significantly reduced compared with that in controls. These results may indicate different patterns of degeneration of cholinergic output structures in PD and DLB. PMID- 24226266 TI - Decreased hypothalamic prohormone convertase expression in huntington disease patients. AB - In Huntington disease (HD), hypothalamic neuropeptidergic systems are not equally affected at the peptide and mRNA levels. Because prohormone convertases (PCs) are critically involved in the conversion of propeptides into their active forms, we postulated that a decrease in PC expression may underlie these discrepancies. Therefore, we assessed the expression of PC1/3 and PC2 in the hypothalamic infundibular, suprachiasmatic, and paraventricular nuclei in postmortem tissues of HD patients and controls (n = 9, each) using immunocytochemistry and quantitative reverse transcription polymerase chain reaction. We also assessed PC1/3 and PC2 mRNA expression in the inferior frontal gyrus and colocalization of both PCs with corticotropin-releasing hormone and alpha-melanocyte-stimulating hormone. In HD patients, PC1/3 and PC2 expression was decreased in the hypothalamic infundibular (both p = 0.046) and paraventricular nuclei (p = 0.031 and p = 0.019). In the suprachiasmatic nucleus, PC1/3 and PC2 expressions were not different between HD and control cases; PC1/3 and PC2 mRNA levels in the inferior frontal gyrus were also not different. None of the PCs was colocalized with corticotropin-releasing hormone, whereas alpha-melanocyte-stimulating hormone showed colocalization with PC1/3 and PC2. These data suggest that defects in the processing of hypothalamic neuropeptides in HD may partially arise from decreased PC1/3 and PC2 expressions. These changes might contribute to selective neuropathology underlying various clinical manifestations and may provide novel therapeutic targets in HD patients. PMID- 24226268 TI - Proteolytic cleavage of polymeric tau protein by caspase-3: implications for Alzheimer disease. AB - Truncated tau protein at Asp(421) is associated with neurofibrillary pathology in Alzheimer disease (AD); however, little is known about its presence in the form of nonfibrillary aggregates. Here, we report immunohistochemical staining of the Tau-C3 antibody, which recognizes Asp(421)-truncated tau, in a group of AD cases with different extents of cognitive impairment. In the hippocampus, we found distinct nonfibrillary aggregates of Asp(421)-truncated tau. Unlike Asp(421) composed neurofibrillary tangles, however, these nonfibrillary pathologies did not increase significantly with respect to the Braak staging and, therefore, make no significant contribution to cognitive impairment. On the other hand, despite in vitro evidence that caspase-3 cleaves monomeric tau at Asp(421), to date, this truncation has not been demonstrated to be executed by this protease in polymeric tau entities. We determined that Asp(421) truncation can be produced by caspase-3 in oligomeric and multimeric complexes of recombinant full-length tau in isolated native tau filaments in vitro and in situ in neurofibrillary tangles analyzed in fresh brain slices from AD cases. Our data suggest that generation of this pathologic Asp(421) truncation of tau in long-lasting fibrillary structures may produce further permanent toxicity for neurons in the brains of patients with AD. PMID- 24226269 TI - Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is pathologically characterized by alpha synuclein aggregates in the brain. Most patients with DLB also show cerebral Alzheimer disease-type pathology (i.e. beta-amyloid plaques and hyperphosphorylated tau deposits). It is unclear whether this overlap is coincidental or driven by specific regional or cellular interactions. The aims of this study were to investigate the regional convergence of alpha-synuclein, tau, and beta-amyloid and to identify patterns of cellular co-occurrence of tau and alpha-synuclein in DLB. The study group consisted of 22 patients who met clinical and neuropathologic criteria for DLB. Protein aggregates were assessed semiquantitatively in 17 brain areas. APOE and MAPT genotypes were determined. Cellular co-occurrence of tau and alpha-synuclein was evaluated by double immunofluorescence. We found that total beta-amyloid pathology scores correlated positively with total alpha-synuclein pathology scores (rho = 0.692, p = 0.001). The factors that correlated best with the amount of alpha-synuclein pathology were the severity of beta-amyloid pathology and presence of the MAPT H1 haplotype. Tau and alpha-synuclein frequently colocalized in limbic areas, but no correlation between total pathology scores was observed. This study confirms and extends the role of beta-amyloid deposition and the MAPT H1 haplotype as contributing factors in DLB pathogenesis and demonstrates the confluence of multiple agents in neurodegenerative diseases. PMID- 24226267 TI - Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum. AB - Traumatic brain injury frequently causes traumatic axonal injury (TAI) in white matter tracts. Experimental TAI in the corpus callosum of adult mice was used to examine the effects on oligodendrocyte lineage cells and myelin in conjunction with neuroimaging. The injury targeted the corpus callosum over the subventricular zone, a source of neural stem/progenitor cells. Traumatic axonal injury was produced in the rostral body of the corpus callosum by impact onto the skull at the bregma. During the first week after injury, magnetic resonance diffusion tensor imaging showed that axial diffusivity decreased in the corpus callosum and that corresponding regions exhibited significant axon damage accompanied by hypertrophic microglia and reactive astrocytes. Oligodendrocyte progenitor proliferation increased in the subventricular zone and corpus callosum. Oligodendrocytes in the corpus callosum shifted toward upregulation of myelin gene transcription. Plp/CreER(T):R26IAP reporter mice showed normal reporter labeling of myelin sheaths 0 to 2 days after injury but labeling was increased between 2 and 7 days after injury. Electron microscopy revealed axon degeneration, demyelination, and redundant myelin figures. These findings expand the cell types and responses to white matter injuries that inform diffusion tensor imaging evaluation and identify pivotal white matter changes after TAI that may affect axon vulnerability vs. recovery after brain injury. PMID- 24226271 TI - Structural and expression differences between the vasculature of pilocytic astrocytomas and glioblastomas. AB - The identification of differences in vascular architecture and utilization of angiogenic pathways is a first step for identifying specific targets for tailored antiangiogenic therapies of brain tumor patients. Here, we compared the proliferating vasculature of 2 glioma subtypes with entirely different biologic behaviors and molecular background at the immunophenotype and gene expression levels. Proliferating vessels in 13 pilocytic astrocytomas and 8 glioblastomas were compared for differences in the composition of the vascular walls using confocal microscopy for markers of endothelial cells and pericytes/mural cells. Endothelial, pericytic, and mural cells had normal-appearing arrangements in the vessels in pilocytic astrocytomas, whereas those in glioblastomas appeared to be more disorganized. In addition, differences in expression of angiogenesis-related genes were sought in the tumor specimens using RNA expression arrays. There were 114 out of 2,894 differentially expressed angiogenesis-related genes between these 2 glioma subtypes indicating differences in the utilization of various pathways. These results point to the need for detailed information on mechanisms of neoangiogenesis in tumor subtypes to facilitate the development of specific antiangiogenic strategies. PMID- 24226270 TI - Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center. AB - To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. PMID- 24226272 TI - Low intensity aerobic exercise and oxidative stress markers in older adults. AB - This comparative study examined the effects of regular low intensity aerobic exercise on oxidative stress markers in older adults. The study was carried out on 15 sedentary subjects (age: 65.1 +/- 3.5 years) versus 18 subjects performing fitness exercises (age: 65.8 +/- 3.3 years). Before and after an incremental exercise test, oxidative stress markers were assessed. Superoxide dismutase was higher at rest and at the recovery for the physically active subjects compared with sedentary subjects (p < .05). At recovery, glutathione peroxidase and alpha Tocopherol increased significantly above the resting values only in the active group (p < .05). Malondialdehyde had increased in both groups (p < .01), associated with a higher level in the sedentary group (p < .05) at the recovery. These data suggest that low intensity aerobic exercise may be useful to prevent the decline of antioxidants linked with aging. PMID- 24226273 TI - Differential protein profile in sexed bovine semen: shotgun proteomics investigation. AB - The preparation of sexed semen is based on the differential DNA content between the X and Y chromosome bearing sperm cells determined by fluorescence-activated cell sorting. In spite of its intrinsic limitations this represents the only effective method. However, the employment of sexed sperm for breeding food producing animals on a large scale requires additional knowledge in the protein repertoire for the development of improved methods to differentiate X and Y sperm cells maintaining high vitality. In order to address this issue, we performed a comparative shotgun proteomic investigation by nUPLC-MS/MS to characterize sexed bovine semen. The protein profiles of these two types of sperm cells have shown differential expression of proteins that may be directly associated with the main components of cytoskeletal structures of flagellum, as the axoneme, outer dense fibers and fibrous sheath, as well as glycolytic enzymes and calmodulin, involved in the energetic metabolism regulation. Overall these results may provide a base to a better comprehension of the biological features of sperm cells and may be useful to the development of alternative methods of separation. PMID- 24226274 TI - Effects ofVerticillium albo-atrum culture filtrate on somatic embryogenesis in alfalfa. AB - Cell suspensions derived from young petioles of alfalfa (Medicago sativa L.) were cultured in the presence and absence of aVerticillium albo-atrum culture filtrate (20% v/v) for 6 cycles. The frequency of somatic embryogenesis and the growth rate of the suspension cultures were investigated at each cycle. Somatic embryogenesis in the filtrate-treated cultures declined but was still at a relatively high level after 6 subcultures, compared to controls cultures which virtually lost the capacity for embryo formation in the same period. The decline in the embryogenic capacity of filtrate treated-cultures was accompanied by a six fold increase in the rate of growth of the cultures. PMID- 24226275 TI - Improved efficiency of the walnut somatic embryo gene transfer system. AB - AnAgrobacterium-mediated gene transfer system which relies on repetitive embryogenesis to regenerate transgenic walnut plants has been made more efficient by using a more virulent strain ofAgrobacterium and vectors containing genes for both kanamycin resistance and beta-glucuronidase (GUS) activity to facilitate early screening and selection. Two plasmids (pCGN7001 and pCGN7314) introduced individually into the disarmedAgrobacterium host strain EHA101 were used as inoculum. Embryos maintained on medium containing 100 mg/l kanamycin after co cultivation produced more transformed secondary embryos than embryos maintained on kanamycin-free medium. Of the 186 GUS-positive secondary embryo lines identified, 70% were regenerated from 3 out of 16 primary embryos inoculated with EHA101/pCGN7314 and grown on kanamycin- containing medium, 28% from 4 out of 17 primary embryos inoculated with EHA101/ pCGN7001 and grown on kanamycin medium, and 2% from one out of 13 primary embryos inoculated with EHA101/pCGN7001 but not exposed to kanamycin. Because kanamycin inhibits but does not completely block new embryo formation in controls, identification of transformants formerly required repetitive selection on kanamycin for several months. Introduction of the GUS marker gene allowed positive identification of transformant secondary embryos as early as 5-6 weeks after inoculation. DNA analysis of a representative subset of lines (n=13) derived from secondary embryos confirmed transformation and provided evidence for multiple insertion events in single inoculated primary embryos. PMID- 24226276 TI - Interspecific somatic hybrids ofRudbeckia hirta andR. Laciniata (Compositae). AB - Interspecific somatic hybrid plants betweenRudbeckia hirta cv. Marmalade andR.laciniata cv. Irish Eyes were regenerated following the electro-fusion of mesophyll protoplasts ofR.hirta with callus protoplasts ofR.laciniata. A hybrid selection scheme was based on the fact that plant regeneration, from parental protoplasts ofR.hirta, was via shoot regeneration of callus, and only via rhizogenesis forR.laciniata. The other half of the selection strategy was based on the presence of anthocyanin-pigmented roots; a characteristic of theR.hirta parent only. Somatic hybrids were regenerated, via rhizogenesis, alongside normalR.laciniata but were distinguished by the presence of pigmented roots (a feature ofR.hirta). Hybrid plants had a floral morphology that was intermediate as compared to that of the two parents, with an expected somatic chromosome number of 2n=(2x+4x)=74. Pollen viability though was low. Esterase and peroxidase isozyme profiles confirmed the hybrid nature of the regenerated plants with pigmented roots, whilst chloroplast DNA restriction analysis showed that these hybrids had aR.laciniata chloroplast DNA. This demonstration of somatic hybridisation not only opens up the possibility of incorporating novel traits between such ornamentalCompositae species, but provides a selection strategy based on rhizogenesis as the route to plant regeneration coupled with heritable pigmentation production of roots as a confirmatory hybrid marker. PMID- 24226277 TI - In vitro clonal multiplication of turmeric (Curcuma spp.) and ginger (Zingiber officinale Rosc.). AB - Rhizome buds, excised from threeCurcuma spp., and ginger, inoculated aseptically on MS medium with varying levels of BAP and kinetin, produced multiple shoots. For shoot multiplication, a concentration of 3.0 mg/l BAP was found to be optimum for all the species.In vitro plants were successfully established in the field and were morphologically uniform. A simple method to extend the subculture interval was used and its relevance to germplasm conservation is discussed. PMID- 24226278 TI - The effects of interactions of culture environment with genotype on wheat (Triticum aestivum) anther culture response. AB - The interactions of genotype and several variables related to culture environment, including temperature pretreatment, conditioned medium and agar concentrations were examined in a series of experiments for their effects on percent anthers producing callus and number of embryoids produced per 100 anthers scored. Significant genotypic interaction was observed for both traits with all environmental variables except methods of medium conditioning. Such interactions involve both changes of response magnitude and changes of rank order of genotypes. The highest response frequencies observed were in excess of 30% of anthers callusing. Most lines examined responded relatively well to a culture regime utilizing a 4 degrees C treatment for 7-14 d prior to anther excision, followed by float culture, without transfer and without preconditioning of the culture medium. The results indicate, however, that particular genotypes may have specific requirements with respect to various environmental conditions so that culture conditions may need to be adjusted, especially for the least responsive genotypes. PMID- 24226279 TI - Production of first and second generations aposporous gametophytes fromPyrrosia piloselloides (L.) Price frond strips cultured in vitro. AB - Second generation aposporous gametophytes were obtained from sporophytes derived from first generation aposporous gametophytes, which in turn came from the mature fronds grown from spores in the laboratory. Murashige and Skoog modified medium in 1% agar supplemented with sugar alcohols (sorbitol, mannitol), auxins (NAA, 2,4-D) and cytokinin (BA) promoted a higher percentage of aposporous development from mature fronds ofPyrrosia piloselloides derived from aseptically cultured spores as compared with those obtained from plants in the field. A method using 4'6-diamidino-2-phenyl indole and fluorescence microscopy correlated the deoxyribonucleic acid contents of the aposporous gametophytes and sporophytes derived from them with their ploidy level. PMID- 24226280 TI - Plant regeneration fromArabidopsis thaliana protoplasts. AB - Arabidopsis thaliana protoplasts, isolated from a cell suspension, regenerated cell walls and then exhibited sustained cell divisions. Within 10 days after isolation as many as 40% of the protoplast-derived cells divided. Protoplast derived calli exhibited a wide range of developmental responses, including apparent embryogenesis. The cell suspension has been cryopreserved. PMID- 24226281 TI - An in vitro method for screening for the presence of thepat-2 gene in tomatoes (Lycopersicon esculentum Mill.). AB - Under field conditions,pat-2, the gene which conditions parthenocarpy in tomatoes, is recessive. A simple method has been devised for distinguishing the heterozygote from the two homozygotes using tissue culture. Ovaries of plants segregating for thepat-2 gene were excised and cultured on a medium containing 100 ppm gibberellic acid. After three weeks in culture, three distinct ovary sizes could be seen. It was shown, using F 3 progeny tests, that the largest ovaries corresponded to those plants homozygous for thepat-2 gene, the smallest ovaries corresponded to those plants homozygous for the wild type allele, and the intermediate sized ovaries were the heterozygotes. The ability to identify the heterozygote would greatly simplify a backcross breeding program aimed at incorporating thepat-2 gene into commercial cultivars by eliminating the need for an F 3 progeny test to determine the genotype of a plant. PMID- 24226282 TI - In situ detection of transposition of the maize controlling element (Ac) in transgenic soybean tissues. AB - The development of a transposon mutagenesis system in soybean would aid in the isolation of unknown genes. The maize controlling element (Ac) has, therefore, been introduced into the soybean (Glycine max (L.) Merr.) genome byAgrobacterium mediated transformation.Ac was inserted into the untranslated leader region of the bacterial beta-glucuronidase gene (GUS) such that the excision ofAc resulted in restoration of the GUS gene activity. Excision events of theAc element were monitored by detecting blue cells or sectors in transgenic soybean tissues. Using the GUS gene assay and with hybridization data, we have demonstrated that theAc element transposes in transgenic soybean calli, leaves, stems, and roots. PMID- 24226283 TI - Cultivation of plant cells in aqueous two-phase polymer systems. AB - Suspension cultures ofNicotiana tabacum have been successfully grown in aqueous, two-phase systems comprised of polyethylene glycol (PEG) and dextran in a modified LS medium. Aqueous two-phase systems may be advantageous for plant tissue cultivation since cells can be immobilized in one phase while secondary products are collected and withdrawn in the other phase, thus enhancing productivity. Culture growth rate was compared in a variety of two-phase systems, covering a range of both polymer molecular weight and concentration. Systems exhibiting relatively higher phase miscibility yielded increased growth rates as compared to less miscible phase formulations. The highest observed growth rate occurred in 3% PEG 20000/5% crude dextran and approached growth rates and cell densities of cultures grown in standard LS medium. PMID- 24226284 TI - Differentiation in explants from mature leguminous trees. AB - Stem and petiole explants, obtained from mature trees, ofAlbizzia lebbeck,Cassia fistula andC.siamea callused and differentiated shoot-buds and later shoots on B5 medium supplemented with either 0.5 mg/l IAA + 1 mg/l BAP or BM + 2 mg/l NAA + 0.5 mg/l BAP. The stem explants were more responsive than the petiole explants. InA.lebbeck, the IAA substituted medium favoured differentiation from both types of explants. However, inC.fistula, the type of explants rather than the medium composition had an overriding influence on shoot differentiation since those from petiole hardly responded in either medium. It has been possible to obtain plantlets from bothA.lebbeck andC.fistula under conditions conducive to rooting. Plantlets ofA.lebbeck have also been successfully transferred to the field. PMID- 24226285 TI - Methylation of ribosomal RNA genes inPetunia hybrida plants, callus cultures and regenerated shoots. AB - The extent of methylation of the 18S-25S ribosomal RNA genes ofPetunia hybrida has been investigated using methylation-sensitive restriction endonucleases and Southern hybridisation. The genes in leaves, ovaries, petals, stigmas, anthers, and seed are methylated to a similar extent, but those in roots are hypomethylated. Genes in adventitious roots formed from stem cuttings are also hypomethylated. Genes in callus cultures initiated from leaf discs vary widely in the extent of methylation, but the pattern obtained is stable during culture. Callus cells containing hypomethylated genes can give rise to shoots in which the extent of methylation has reverted to that of the original leaf explant. These results demonstrate the striking plasticity of ribosomal RNA gene methylation inPetunia. PMID- 24226286 TI - Somaclonal variant plants of wheat derived from mature embryo explants of three genotypes. AB - Somaclones regenerated from three wheat (Triticum aestivum L.) cultivars, Glennson, Pavon and PAK-16171 were evaluated for variation in agronomic and morphological characters. Calli were initiated from germinating seeds on Linsmaier and Skoog (LS) medium plus 2 mg/l 2,4-dichlorophenoxyacetic acid, 2% sucrose and 1% agar. Calli were isolated and regenerated into whole plants on LS medium containing 0.1 mg/l indole - 3-acetic acid and 0.5 mg/l benzyladenine. Comparisons among the somaclones and their parents were made for plant height, spike length, number of grains per spike, and 100 grain weight. Significant variation was observed in these characters between the somaclones and parents. Genotypic differences were observed among the somaclones for many of these agronomic and morphological characters. PMID- 24226287 TI - Glutathione-elicited changes in chromatin structure within the promoter of the defense gene chalcone synthase. AB - Sites hypersensitive to digestion by DNase I have been identified within the 5' flanking and 3'-coding sequences of genes encoding the defense enzyme chalcone synthase in bean (Phaseolus vulgaris L.). Two of the 5'-flanking hypersensitive sites are markedly induced upon elicitation of cells with glutathione and delineate sequence elements that are also present in the promoters of coordinately regulated genes. In contrast, other hypersensitive sites within the 5'-flanking sequences are expressed constitutively and one maps within an element that is also present in the promoters of coordinately regulated genes. These results suggest that the transcriptional activation of chalcone synthase genes is accompanied by structural changes in the chromatin associated with the proximal region of the promoter and that these probably reflect the binding of transcription factors tocis-regulatory elements. PMID- 24226288 TI - Root hair protoplasts ofLotus corniculatus L. (birdsfoot trefoil) express their totipotency. AB - Treatment of the roots of 24-48 h old seedlings of the forage legumeLotus corniculatus with 1.0% Cellulase YC, and 0.1% Pectolyase Y-23 in 4.2% mannitol solution released protoplasts from the tips of root hairs within 30-40 sec of enzyme incubation. Roots from approximately 1000 seedlings yielded 1.7*10(5) protoplasts. Ten percent of protoplasts divided to form cell colonies when cultured at 1.0*10(5) ml(-1) in droplets of KM8P medium with 0.6% Sea Plaque agarose. Colonies formed callus on UM agar medium; protoplast-derived tissues produced shoots on B5 medium containing 0.05 mg 1(-1) of BAP. Regenerated plants were phenotypically and cytologically normal (2n=2x=24+/-2), and produced nitrogen fixing root nodules following inoculation withRhizobium. These results confirm the totipotency of protoplasts isolated from specialised epidermal cells of seedling roots ofLotus corniculatus. PMID- 24226289 TI - The ROC program: accelerated restoration of competency in a jail setting. AB - In 29 months of operation, the restoration of competency (ROC) program provided treatment services to 192 incompetent to stand trial patients in a jail setting. The ROC restored competency for 55% of the patients in an average of 57 days compared to the state hospital average of 180 days. The average cost of treatment/restoration per admission was $15,568 compared to the state hospital average of $81,000. The ROC model accelerates needed treatment for mentally ill defendants, cuts demand for costly state hospital forensic beds, and assists jails in better managing inmates with severe psychiatric disorders--yielding major cost savings and improved care. In addition to preventing readmissions and negative behavioral episodes, the ROC improved the broader forensic system by eliminating the state hospital waiting list, accelerating access to psychiatric services, promoting local access for lawyers and family, and gaining stakeholder satisfaction. PMID- 24226290 TI - Central nervous system involvement in scrub typhus. AB - Scrub typhus is an emerging infectious disease in India. Among its protean clinical manifestations, central nervous system involvement is common. In this prospective observational study, altered sensorium, headache, seizures and aseptic meningitis were found to be common central nervous system manifestations. Prompt treatment with doxycycline reduces morbidity and mortality. PMID- 24226291 TI - Primary hydatid disease of brachialis and biceps brachii muscles: a case report. AB - Primary hydatid cyst of the skeletal muscle is very rare and accounts for less than 1% of all cases. It is often asymptomatic and can pose diagnostic problems. Accurate diagnosis should be made using ultrasonography and magnetic resonance imaging. Proper treatment should be a wide surgical resection of the localized muscle with the aid of antihelmintic chemotherapy pre- and postoperatively. We report a case of primary hydatic cyst located simultaneously in both the biceps brachii and brachialis muscles, treated with wide resection surgery and pre- and postoperative anthelmintic chemotherapy. PMID- 24226292 TI - Bleeding after expandable nitinol stent placement in patients with esophageal and upper gastrointestinal obstruction: incidence, management, and predictors. AB - BACKGROUND: Placement of self-expandable nitinol stents is useful for the treatment of esophageal and upper gastrointestinal (GI) obstruction. However, complications such as stent migration, tumor overgrowth, and bleeding occur. Although stent migration and tumor overgrowth are well documented in previous studies, the occurrence of bleeding has not been fully evaluated. PURPOSE: To evaluate the incidence, management strategies, and predictors of bleeding after placement of self-expandable nitinol stents in patients with esophageal and upper GI obstruction. MATERIAL AND METHODS: We retrospectively reviewed the medical records and results of computed tomography and endoscopy of 1485 consecutive patients with esophageal and upper GI obstructions who underwent fluoroscopically guided stent placement. RESULTS: Bleeding occurred in 25 of 1485 (1.7%) patients 0 to 348 days after stent placement. Early stent-related bleeding occurred in 10 patients (40%) and angiographic embolization was used for 5/10. Late bleeding occurred in 15 patients (60%) and endoscopic hemostasis was used for 7/15. Twenty two of 25 (88%) patients with bleeding had received prior radiotherapy and/or chemotherapy. CONCLUSION: Bleeding is a rare complication after placement of expandable nitinol stents in patients with esophageal and upper GI obstruction, but patients with early bleeding may require embolization for control. Care must be exercised on placing stents in patients who have received prior radiotherapy or chemotherapy. PMID- 24226293 TI - Latest developments in the imaging of fibrotic liver disease. AB - According to the World Health Organization, liver cirrhosis accounted for 1.8% of all deaths in Europe, causing about 170,000 deaths per year. Approximately 29 million persons in the EU suffer from chronic liver disease and this trend is on the rise. Liver disease is the EU's fifth most common cause of death accounting for at least one in six deaths. Early detection and monitoring of fibrosis has the potential to direct management of these chronic liver diseases and avert morbidity and mortality. Although the available techniques are in their infancy and the very early stages of fibrosis are difficult to detect, there have been significant advances in imaging over the last decade that has resulted in the use of these new imaging techniques being introduced into the patient pathway. This review explores the accuracies of these imaging techniques, their role in the management of patients, and the potential for the future. PMID- 24226294 TI - Percutaneous embolization of symptomatic dissecting aneurysms of the celiac artery. AB - BACKGROUND: Isolated spontaneous dissection of visceral arteries, not associated with aortic dissection, is a rare condition. To date, there is no consensus on the optimal treatment strategy. PURPOSE: To investigate the feasibility, efficacy, and safety of percutaneous embolization for the treatment of isolated and symptomatic dissecting aneurysm of the celiac artery. MATERIAL AND METHODS: From March 2010 to October 2011, four patients were diagnosed at our institution with symptomatic dissecting aneurysm of the celiac trunk. All patients had acute abdominal pain, two had intra-abdominal hemorrhage and bleeding shock. Three patients underwent elective "trapping" embolization of the celiac trunk with Amplatzer vascular plugs in the hepatic and splenic artery and celiac trunk, and coils in left gastric artery. One patient had a splenic artery rupture and underwent selective embolization of this vessel with platinum-fiber coils. RESULTS: Angiography and postoperative CT scan confirmed artery occlusion after embolization in all cases. Revascularization of celiac trunk branches was obtained via collaterals. No procedure-related adverse events occurred during follow-up (median, 4.5 months; range, 3-24 months) and vessel occlusion was maintained. CONCLUSION: Isolated and symptomatic dissecting aneurysm of the celiac trunk can be successfully managed by embolization techniques with good short- to mid-term results. PMID- 24226295 TI - The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy. AB - Invasion and metastasis are the main causes of treatment failure and death in breast cancer. Thus, novel invasion-based therapies such as those involving natural agents are urgently required. In this study, we examined the effects of magnolol (Mag), a compound extracted from medicinal herbs, on breast cancer cells in vitro and in vivo. Highly invasive cancer cells were found to be highly sensitive to treatment. Mag markedly inhibited the activity of highly invasive MDA-MB-231 cells. Furthermore, Mag significantly downregulated matrix metalloproteinase-9 (MMP-9) expression, an enzyme critical to tumor invasion. Mag also inhibited nuclear factor-kappaB (NF-kappaB) transcriptional activity and the DNA binding of NF-kappaB to MMP-9 promoter. These results indicate that Mag suppresses tumor invasion by inhibiting MMP-9 through the NF-kappaB pathway. Moreover, Mag overcame the promoting effects of phorbol 12-myristate 13-acetate (PMA) on the invasion of MDA-MB-231 cells. Our findings reveal the therapeutic potential and mechanism of Mag against cancer. PMID- 24226297 TI - An effort to 'leverage' the effect of participation in a mass event on physical activity. AB - Despite the considerable interest in community-based physical activity (PA) interventions, there is a lack of clarity on which strategies are most effective and most likely to work in different contexts. The purpose of this study was to use existing community resources to promote PA in a population sample of insufficiently active women using a cluster RCT design. Participants (n = 402) were grouped into 32 geographical-based clusters, which were randomly allocated into 16 intervention (n = 193) and 16 control (n = 209) regions. The intervention was delivered in conjunction with regional units of the Irish Sports Council; participants received a pack containing tailored information about local PA options in their community, training plans, stage-matched behaviour change booklets and a pedometer. Control participants received health promotion leaflets. Evaluation was conducted using the RE-AIM framework to assess both effectiveness and generalizability. Repeated measures ANOVAs with adjustment for clustering revealed that both groups displayed an approximate 39 min increase in PA, but decreases in sitting were greater in the intervention group than the control group (32.9 versus 1.2 min). Recall of materials was high ranging between 85 and 97% for the various intervention components. Finally, those who received higher doses of the intervention (three or more components) reported an approximate 50 min increase in PA compared with 18 min among those who did not use any aspect of the intervention. While no clear intervention effect was evident, this research was successful in linking and implementing good research design with PA promoting networks. PMID- 24226296 TI - Extensive lesions in the gustatory cortex in the rat do not disrupt the retention of a presurgically conditioned taste aversion and do not impair unconditioned concentration-dependent licking of sucrose and quinine. AB - Although damage to gustatory cortex (GC) in the rat has been reported to severely impair, if not eliminate, retention of a presurgically conditioned taste aversion (CTA), it has equivocal effects on taste preference as measured by intake tests. Because intake tests can be influenced by nongustatory (e.g., postingestive) factors, we employed the brief-access taste test to assess the effects of ibotenic acid-induced lesions targeting the GC on unconditioned licking to a sucrose and then a quinine concentration series in a specialized lickometer. As a functional lesion assessment, a presurgical CTA to 0.1M NaCl was established in thirsty rats by following 15-min intake with intraperitoneal administration of either LiCl (or NaCl for control) on 2 occasions. Both conditioned sham-operated (SHAM) rats and rats with histologically confirmed extensive damage to the GC (GCX) avoided a NaCl concentration series relative to unconditioned controls in a postsurgical brief-access CTA test, with no difference between the surgical groups in their responses to NaCl or similar concentrations of KCl. GCX rats also did not differ from SHAM rats in the EC50 of concentration-response functions for sucrose or quinine. Clearly, the critical cortical area required for the retention of a presurgical CTA falls outside of the extensive area of damage, which was well centered within the conventionally defined gustatory zone of the insular cortex. The absence of an effect on unconditioned responsiveness to sucrose and quinine suggests that the damaged region is also unnecessary for the normal expression of affective licking responses to tastants. PMID- 24226298 TI - Protein synthesis in tissues of fed and starved carp, acclimated to different temperatures. AB - The temperature dependence of the rates of protein synthesis in the red and white skeletal muscle of the carp (Cyprinus carpio) was measured using a method which involved a single injection of tritiated phenylalanine. Plasma and muscle-free phenylalanine quickly reached a plateau level at all temperatures. During the plateau phase the incorporation of label into protein was liner. Muscle from fish previously acclimated to either a low temperature (8 degrees C) or a high temperature (28 degrees C), showed marked differences in the rates of protein synthesis. The results show that cold acclimation is associated with significantly higher rates of protein synthesis (p<0.001) in both red and white muscle. Arrhenius activation energies, derived from the rates of protein synthesis at the different experimental temperatures, were similar for both red and white muscle in fish acclimated to warm or cold temperatures. Measurements for both acclimated groups over the temperature range 8-34 degrees C showed that the activation energy for the process of protein synthesis was 86.7 kJ/mol and 78.7 kJ/mol for the red and white muscle respectively. PMID- 24226299 TI - Isolation and partial characterization of a novel keratan sulfate proteoglycan from metamorphosing bonefish (Albula) larvae. AB - Proteoglycans (PGs) were isolated from leptocephalous larvae of the bonefish (Albula sp.), which were in the early stages of metamorphosis, using both associative and dissociative conditions in the presence of protease inhibitors. The procedure was rapid and resulted in an extraction efficiency of 75% (associative) and 85-90% (dissociative). The majority of co-extracted protein could be effectively separated from the PGs by utilizing either Sepharose CL-2B or CL-6B gel chromatography. Sepharose CL-2B chromatography of extracted PGs after treatment with bacterial keratan sulfate-endo-beta-galactosidase (keratanase) showed that most of the high molecular weight (M r) carbohydrate was degraded. Free keratan sulfate (KS) chains were prepared from whole-larva extracts (which also contain small amounts of chondroitin sulfate) by both chondroitinase ABC treatment and ethanol fractionation. Sepharose CL-6B chromatography under dissociative conditions showed that larval KS chains were much larger (M r~55,000) than those from cornea. These chains tended to aggregate when chromatographed under associative conditions. Larval KS was degraded by keratanase and resistant to chondroitinase, ABC and testicular hyaluronidase. Differences were also noted in the oligosaccharides produced by keratanase treatment of the two preparations. However, biochemical composition of larval and corneal KS was similar. PMID- 24226300 TI - Effects of prolonged epinephrine infusion on blood respiratory and acid-base states in the rainbow trout: Alpha and beta effects. AB - Rainbow trout were infused continuously for 12h with epinephrine in the presence or absence of alpha-and/or beta-adrenergic blockade to characterize the specific adrenergic mechanisms involved in the control of blood acid-base status and oxygen transport capacity. Infusion of epinephrine, alone, produced a transient respiratory acidosis, as indicated by an increase in carbon dioxide tension and a decrease in whole blood pH, yet arterial oxygen tension was elevated. Red blood cell pH increased by approximately 0.2 pH units during epinephrine infusion and this increase as well as the increase in oxygen tension were prevented by pretreatment with propranolol (a beta-adrenergic antagonist). Epinephrine infusion during alpha-adrenergic blockade caused a prolonged elevation of blood carbon dioxide tension and abolished the increases in hematocrit and hemoglobin concentrations observed during epinephrine infusion alone. Infusion of the alpha adrenergic agonists phenylephrine (an alpha1 agonist) or clonidine (an alpha2 agonist) caused respiratory acidosis (decreased pH, increased CO2 tension) and a reduction in oxygen tension. Infusion of isoprenaline (a non-specific beta agonist) caused delayed increases in carbon dioxide and oxygen tensions. We speculate that the increased carbon dioxide tension observed during epinephrine infusion is a result of beta-adrenoceptor mediated inhibition of red blood cell bicarbonate dehydration and not branchial convective or diffusive adjustments. The effects of epinephrine on blood O2 tension, content and carrying capacity are discussed with reference to the participation of alpha- and beta-adrenergic mechanisms at the gill, spleen and red blood cell. PMID- 24226302 TI - Referees of articles submitted to the Journal in 1987. PMID- 24226301 TI - Cardiac, ventilatory and metabolic responses of two ecologically dissimilar species of fish to waterborne cyanide. AB - Changes in heart rate, ventilatory activity and oxygen consumption were determined in trout (Salmo gairdneri) and brown bullhead catfish (Ictalurus nebulosus) during exposure to a steadily increasing concentration of waterborne cyanide selected to produce death in 8-9 hours for each species. The lethal cyanide concentration for the bullheads was an order of magnitude higher than for trout. Trout developed an immediate and gradually increasing bradycardia throughout the exposure period. Cyanide produced tachycardia in the bullhead followed by a gradual onset of bradycardia as the concentration of cyanide was raised. Pericardial injection of atropine (a muscarinic cholinergic antagonist) indicated that bradycardia in the trout was due initially to increased vagal tone but later due to the direct effect of cyanide on the heart. Hyperventilation in the trout persisted throughout the exposure period, although the rate and amplitude fluctuated and was variable between individual fish. During the last hour of exposure (highest cyanide concentration), ventilation was characterized by rapid, shallow breaths followed by a sudden respiratory arrest. The bullheads exhibited hyperventilation during the first 3 hours of exposure followed by a gradual, linear drop in ventilation rate and amplitude until death occurred. Cardiac and ventilatory responses in both species were attributed to stimulation of central and peripheral chemoreceptors by cyanide. Evidence is presented which suggests the initial response in the bullheads was due, at least in part, to gustatory stimulation by the cyanide. Oxygen consumption of the trout remained above pre-exposure levels for the majority of the test period. Oxygen consumption in the bullhead paralleled the changes in heart and ventilatory rates. Whole-body lactate levels of fingerlings of both species during cyanide exposure were measured to estimate the extent of anaerobiosis. Whole-body lactate levels were much greater in the bullheads than the trout, indicating a higher capacity for anaerobiosis, possibly due to a greater fuel supply. Overall, the trout responded to cyanide in a manner similar to that produced by environmental hypoxia whereas the bullheads experienced a gustatory stimulus which masked the hypoxia-like response. PMID- 24226303 TI - Erratum. PMID- 24226304 TI - Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography. AB - BACKGROUND: Among physicians who perform endoscopic retrograde cholangiopancreatography (ERCP), the relationship between procedure volume and outcome is unknown. OBJECTIVE: Quantify the ERCP volume-outcome relationship by measuring provider-specific failure rates, hospitalization rates, and other quality measures. RESEARCH DESIGN: Retrospective cohort. SUBJECTS: A total of 16,968 ERCPs performed by 130 physicians between 2001 and 2011, identified in the Indiana Network for Patient Care. MEASURES: Physicians were classified by their average annual Indiana Network for Patient Care volume and stratified into low (<25/y) and high (>=25/y). Outcomes included failed procedures, defined as repeat ERCP, percutaneous transhepatic cholangiography or surgical exploration of the bile duct<=7 days after the index procedure, hospitalization rates, and 30-day mortality. RESULTS: Among 15,514 index ERCPs, there were 1163 (7.5%) failures; the failure rate was higher among low (9.5%) compared with high volume (5.7%) providers (P<0.001). A second ERCP within 7 days (a subgroup of failure rate) occurred more frequently when the original ERCP was performed by a low-volume (4.1%) versus a high-volume physician (2.3%, P=0.013). Patients were more frequently hospitalized within 24 hours when the ERCP was performed by a low volume (28.3%) versus high-volume physician (14.8%, P=0.002). Mortality within 30 days was similar (low=1.9%, high=1.9%). Among low-volume physicians and after adjusting, the odds of having a failed procedure decreased 3.3% (95% confidence interval, 1.6%-5.0%, P<0.001) with each additional ERCP performed per year. CONCLUSIONS: Lower provider volume is associated with higher failure rate for ERCP, and greater need for postprocedure hospitalization. PMID- 24226305 TI - Surgeons' perceptions of public reporting of hospital and individual surgeon quality. AB - BACKGROUND: Hospital-specific and surgeon-specific public reporting of performance measures is expanding largely due to calls for transparency from the public and oversight agencies. Surgeons continue to voice concerns regarding public reporting. Surgeons' perceptions of hospital-level and individual-level public reporting have not been assessed. This study (1) evaluated surgeons' perceptions of public reporting of surgical quality; and (2) identified specific barriers to surgeons' acceptance of public reporting. METHODS: All surgeons (n=185) at 4 hospitals (university, children's, 2 community hospitals), representing all surgical specialties, received a 41-item anonymous Internet based survey. Twenty follow-up qualitative interviews were conducted to assess surgeons' interpretation of findings. RESULTS: The survey response rate was 66% (n=122). Most surgeons supported public reporting of quality metrics at the hospital level (80%), but opposed individual reporting (53%, P<0.01). Fewer surgeons expected that individual (26%) or hospital (47%) public reporting would improve outcomes (P<0.01). Few indicated that their practice would change with hospital (11%) or individual (18%) public reporting (P=0.20). Primary concerns regarding public reporting at the hospital level included patients misinterpreting data, surgeons refusing high-risk patients, and outcome metric validity. Individual-surgeon level concerns included outcome metric validity, adequate sample sizes, and patients misinterpreting data. To make public reporting more acceptable, surgeons recommended patient education, simplified data presentation, continued risk-adjustment refinement, and internal review before public reporting. CONCLUSIONS: Surgeons expressed concerns about public reporting of quality metrics, particularly reporting of individual surgeon performance. These concerns must be addressed to gain surgeons' acceptance and to use public reporting to improve health care quality. PMID- 24226306 TI - The impact of technology diffusion on treatment for prostate cancer. AB - BACKGROUND: The use of local therapy for prostate cancer may increase because of the perceived advantages of new technologies such as intensity-modulated radiotherapy (IMRT) and robotic prostatectomy. OBJECTIVE: To examine the association of market-level technological capacity with receipt of local therapy. DESIGN: Retrospective cohort. SUBJECTS: Patients with localized prostate cancer who were diagnosed between 2003 and 2007 (n=59,043) from the Surveillance Epidemiology and End Results-Medicare database. MEASURES: We measured the capacity for delivering treatment with new technology as the number of providers offering robotic prostatectomy or IMRT per population in a market (hospital referral region). The association of this measure with receipt of prostatectomy, radiotherapy, or observation was examined with multinomial logistic regression. RESULTS: For each 1000 patients diagnosed with prostate cancer, 174 underwent prostatectomy, 490 radiotherapy, and 336 were observed. Markets with high robotic prostatectomy capacity had higher use of prostatectomy (146 vs. 118 per 1000 men, P=0.008) but a trend toward decreased use of radiotherapy (574 vs. 601 per 1000 men, P=0.068), resulting in a stable rate of local therapy. High versus low IMRT capacity did not significantly impact the use of prostatectomy (129 vs. 129 per 1000 men, P=0.947) and radiotherapy (594 vs. 585 per 1000 men, P=0.579). CONCLUSIONS: Although there was a small shift from radiotherapy to prostatectomy in markets with high robotic prostatectomy capacity, increased capacity for both robotic prostatectomy and IMRT did not change the overall rate of local therapy. Our findings temper concerns that the new technology spurs additional therapy of prostate cancer. PMID- 24226307 TI - Rate of utilization and determinants of withdrawal of care in acute ischemic stroke treated with thrombolytics in USA. AB - BACKGROUND: Our current practices for utilization of thrombolytics are based on results of clinical trials with no or restricted use of "withdrawal of care" among treated patients. The increasing use of "withdrawal of care" in routine practice may lead to suboptimal outcomes among acute ischemic stroke patients. METHODS: We determined the frequency of "withdrawal of care" and determined demographic and clinical characteristics, and in-hospital outcomes among thrombolytic-treated ischemic stroke patients stratified by use of "withdrawal of care" using National Inpatient Sample data files from 2002 to 2010. RESULTS: "Withdrawal of care" during hospitalization was instituted in 4287 (3.3%) of the 130,437 acute ischemic stroke patients treated with thrombolytics. In the stepwise logistic regression analysis, women [odds ratio (OR) 1.2, 95% confidence interval (CI), (1.0-1.5)], presence of atrial fibrillation [OR 1.2, 95% CI, (1.0 1.5)], hemiplegia/hemiparesis [OR 1.4, 95% CI, (1.1-1.7)], aphasia [OR 1.2, 95% CI, (1.0-1.5)], and postthrombolytic intracerebral hemorrhage (OR 1.5, 95% CI, 1.1-1.8) were significant predictors of "withdrawal of care" among thrombolytic treated ischemic stroke patient. Hospitals located in the west region [OR 1.7, 95% CI, (1.2-2.4)], and teaching hospitals [OR 1.4, 95% CI, (1.0-1.8)] were more likely to use withdrawal of care. In-hospital mortality (61% vs. 9.0%, P<=0.0001) were higher among those with "withdrawal of care." CONCLUSIONS: Several individual-related and institution-related factors were associated with the use of "withdrawal of care" among thrombolytic-treated ischemic stroke patients. The excessively high mortality and resource utilization mandates a more evidence based policy for "withdrawal of care" in these patients. PMID- 24226308 TI - Prevalence, risk, and correlates of posttraumatic stress disorder across ethnic and racial minority groups in the United States. AB - OBJECTIVES: We assess whether posttraumatic stress disorder (PTSD) varies in prevalence, diagnostic criteria endorsement, and type and frequency of potentially traumatic events (PTEs) among a nationally representative US sample of 5071 non-Latino whites, 3264 Latinos, 2178 Asians, 4249 African Americans, and 1476 Afro-Caribbeans. METHODS: PTSD and other psychiatric disorders were evaluated using the World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) in a national household sample that oversampled ethnic/racial minorities (n=16,238) but was weighted to produce results representative of the general population. RESULTS: Asians have lower prevalence rates of probable lifetime PTSD, whereas African Americans have higher rates as compared with non-Latino whites, even after adjusting for type and number of exposures to traumatic events, and for sociodemographic, clinical, and social support factors. Afro-Caribbeans and Latinos seem to demonstrate similar risk to non-Latino whites, adjusting for these same covariates. Higher rates of probable PTSD exhibited by African Americans and lower rates for Asians, as compared with non-Latino whites, do not appear related to differential symptom endorsement, differences in risk or protective factors, or differences in types and frequencies of PTEs across groups. CONCLUSIONS: There appears to be marked differences in conditional risk of probable PTSD across ethnic/racial groups. Questions remain about what explains risk of probable PTSD. Several factors that might account for these differences are discussed, as well as the clinical implications of our findings. Uncertainty of the PTSD diagnostic assessment for Latinos and Asians requires further evaluation. PMID- 24226309 TI - Telephone-based motivational interviewing to promote physical activity and stage of change progression in older adults. AB - This study examined the efficacy of motivational interviewing (MI) for increasing physical activity in aging adults. Eighty-six participants aged 55 years and older were randomly assigned to receive either four weekly sessions of telephone based MI for increasing physical activity, or a healthy activity living guide (information only control). Changes from baseline weekly caloric expenditure from physical activity, self-efficacy for physical activity, and stage of change for physical activity were compared across groups at posttreatment and six months follow-up. Results indicated that MI participants had higher weekly caloric expenditures from physical activity at posttreatment, but not at six months follow-up; higher self-efficacy for physical activity at six months follow-up; and demonstrated greater stage of change progression across assessments. These findings support the use of telephone-based MI for increasing physical activity in older adults in the short-term. Future studies will need to determine if follow-up booster sessions increase long-term efficacy. PMID- 24226310 TI - The doctor personality--does it exist? PMID- 24226311 TI - Norway and the goat kid that refused to count. PMID- 24226312 TI - [Better knowledge about pain management]. PMID- 24226313 TI - [Blood Pressure Treatment--towards consensus on many things]. PMID- 24226314 TI - [B. Gjelsvik replies]. PMID- 24226315 TI - [Changes within analytical variation]. PMID- 24226316 TI - [R.J. Ulvik replies]. PMID- 24226319 TI - [The law and the budget]. PMID- 24226320 TI - [Budget or estimates]. PMID- 24226321 TI - [M. Halvorsen replies]. PMID- 24226322 TI - [The origin of the word "quarantine"]. PMID- 24226323 TI - [E. Hem replies]. PMID- 24226324 TI - [Long-acting naltrexone--a new way out of opiate addiction?]. PMID- 24226325 TI - [The lyme borreliosis controversy]. PMID- 24226326 TI - [New guidelines for intravenous fluid therapy for children]. PMID- 24226328 TI - [Notification of highly deviant biochemical analysis results]. PMID- 24226327 TI - Long-acting injectable olanzapine can give rise to a condition consistent with central anticholinergic syndrome. PMID- 24226329 TI - [New recommendations for the interpretation of troponin values]. PMID- 24226332 TI - Treatment of type 1 diabetes in the specialist health service--data from the Norwegian Diabetes Register for Adults. AB - BACKGROUND: The Norwegian Diabetes Register for Adults was established in 2005. The aim of the study is to assess the quality of treatment for adult patients with type 1 diabetes in the specialist health service based on register data. MATERIAL AND METHOD: We included patients >= 18 years with type 1 diabetes in the specialist health service for whom the register has data for the period from 1 July 2010-to 31 December 2011. The patients were asked to consent to the transfer of data to the register when they attended a routine consultation. As of 31 December 2011, 95% of the patients asked gave their consent. It is not known how large a proportion of patients were asked. RESULTS: We included the last registered data for 3,697 patients (46.8% women) from 24 outpatient clinics and specialist centres. The average age was 41.8 years and the average duration of diabetes was 20.8 years. Median HbA1c, systolic blood pressure and LDL cholesterol were 8.0%, 126 mm Hg and 2.8 mmol/l respectively. 9.8% achieved all treatment targets set out in the national guidelines for diabetes. 18% had HbA1c <= 7.0%, while 22% had HbA1c >= 9%. 39% of patients on statin therapy achieved the treatment target for LDL cholesterol. 19.6% smoked on a daily basis. 14.9% had received treatment for retinopathy and 5.8% had experienced coronary heart disease. There was no record of foot examination or ophthalmoscopy being performed in 33% and 29% of patients. INTERPRETATION: The preliminary register data indicate that diabetes treatment should be improved both with respect to the implementation of recommended procedures and the proportion of patients who achieve the treatment targets. PMID- 24226333 TI - Late onset metastases to the thyroid gland from renal carcinoma. AB - BACKGROUND: Metastases from renal cell carcinoma to the thyroid gland are uncommon and the clinical course often prolonged. We wished to determine the incidence of such metastases in surgical biopsy records from two Norwegian hospitals. MATERIAL AND METHOD: The archives of the Department of Pathology at Nordland Hospital Bodo (for the period 2002-11) and the Department of Pathology and Medical Genetics at St. Olav's Hospital (for the period 1986-2011) were searched for possible metastases from renal cell carcinoma to the thyroid gland. Biopsy and clinical records were later reviewed to determine sex, age, symptoms, the results of preoperative examinations, tumour size, immune profile and treatment, as well as subsequent clinical course and survival. RESULTS: The biopsy records of five patients, four females and one male, between the ages of 58 and 89 years showed metastases in the thyroid gland that were morphologically and immunohistochemically identical to the renal cell carcinomas that had previously been removed from these patients. A considerable length of time had elapsed, up to 25 years (median 21 years), before the metastases appeared and gave rise to clinical symptoms. All of the patients underwent surgery. Survival following hemithyroidectomy ranged from two months to 13 years. One patient was still alive when the material was reviewed. INTERPRETATION: Metastases from renal clear cell carcinoma to the thyroid gland can occur many years after removal of the primary tumour and produce clinical symptoms such as multinodular goitres. Surgery is indicated if there are no other metastases. The prognosis is good in some patients. PMID- 24226334 TI - [Transcranial direct current stimulation for chronic pain]. AB - BACKGROUND: Transcranial Direct Current Stimulation (tDCS) is a non-invasive method for neuromodulation. By changing the neurons' resting membrane potential, the method can alter the activity in areas of the brain. We therefore wished to review randomised controlled trials (RCTs) that investigate the treatment effect of tDCS on chronic pain. EVIDENCE: We undertook a search in PubMed with the search terms "transcranial direct current stimulation" and "pain", with "randomized controlled trial" as a filter. RESULTS: Five randomised, controlled trials that used quantitative outcome measures for pain were identified. The studies focused on strongly varying groups of patients suffering from pain. The results from some of the studies showed that stimulation with the aid of tDCS led to a significantly lower level of pain, but seen as a whole, the results were not conclusive. INTERPRETATION: The method should be further investigated in studies that include clearly defined groups of patients suffering from pain, as well as a larger number of participants, before implementation of the method is considered as a treatment option for chronic pain. PMID- 24226335 TI - [A horseshoe-shaped wound on the back]. PMID- 24226336 TI - [A man in his 50s with incontinence, difficulty walking and hypernatremia]. PMID- 24226337 TI - [Think holistically, think cooperation]. PMID- 24226338 TI - Irritable bowel syndrome--a microbial perspective. PMID- 24226339 TI - [Confounder in Norwegian]. PMID- 24226342 TI - [National guidelines for the interpretation of troponin values in the diagnosis of acute myocardial infarction]. PMID- 24226343 TI - Notification of highly abnormal laboratory results to doctors outside hospitals. PMID- 24226344 TI - Selection index: economic weights for maximum simultaneous genetic gain. AB - Selection indices that maximize the correlation between an individual organism's index score and its breeding value frequently require a priori known "economic" weights before the optimum phenotypic weights can be estimated. The long generation intervals and economic uncertainty that surround forest tree breeding can make the choice of weights arbitrary. In this paper an algorithm is introduced for finding "economic" weights that will ensure maximum simultaneous progress in all index traits. At the outset the traits are assumed to be of equal preference. The solutions are functions of the eigenvalues and eigenvectors of a quadratic form of the additive genetic and phenotypic covariance matrices. Examples of applications in tree breeding emphasize the practical aspects of the method. PMID- 24226345 TI - Genetic characterisation of a further homoeoallelic series of grain esterase loci,Est-6, in wheat. AB - Isoelectric focussing in alkaline pH gels has permitted the identification of a new homoeoallelic series of genes,Est-6, encoding grain esterases in bread wheat,Triticum aestivum. Nullisomic analysis located these genes to the short arms of the homoeologous group 2 chromosomes. A search for polymorphism withinEst 6 revealed null alleles at each ofEst-A6,Est-B6 andEst-D6. A further homoeolocus,Est-M6, is present on chromosome arm2MS ofAegilops comosa. PMID- 24226346 TI - Protein polymorphism in sugarcane revealed by two-dimensional gel analysis. AB - In order to identify molecular markers for the analysis of the sugarcane genome, proteins extracted from apical segments of shoot tissues were resolved by a combination of equilibrium (IEF) and nonequilibrium (NEPHGE) two-dimensional polyacrylamide gel electrophoresis. A number of taxa of the "Saccharum complex" group (Saccharum species and the related genera of Andropogoneae) with presumed contributions to the sugarcane genome were surveyed. Protein profiles were compared to a reference map consisting of 1,482 protein spots from the noble cane,Saccharum officinarum L. Fifty-three polypeptides, representing about 3.6% of the total resolved spots, showed interspecific variation, whereas 78 polypeptides, about 5.3% of the total, showed intergeneric variation. Of the total polymorphic protein spots, qualitative (presence/absence) variation was more prevalent among the wild than among the cultivated species of the genusSaccharum, but the quantitative (spot intensity) variation was similar for both groups. The population of protein spots showing qualitative and quantitative variations was similar among the related genera of Andropogoneae. These polymorphic proteins can be used in genetic and evolutionary studies of the sugarcane genome. PMID- 24226347 TI - The genetical control of tissue-specific peroxidases,Per-1,Per-2,Per-3,Per-4, andPer-5 in wheat. AB - Isoelectric focusing (IEF) of extracts from different tissues of hexaploid wheat cv "Chinese Spring" provided a method of distinguishing and identifying the four known, and one newly discovered, sets of genes encoding peroxidase isozyme production.Per-1, carried on the short arms of homoeologous group 1 chromosomes, shows a high degree of conservation and is active in coleoptile tissue.Per-2, carried on the short arms of group 2 chromosomes, shows some polymorphism and is most active in root tissue.Per-3, on the long arms of group 3 chromosomes, is highly variable and most active in embryo tissue.Per-4, carried on chromosome arms7AS,4AL, and7DS, is quite variable and most active in endosperm tissue. (The chromosome nomenclature used in this paper is that agreed to by the 7th International Wheat Genetics Symposium, where the previous designations of4A and4B were reversed.) Restriction fragment length polymorphism (RFLP)-based maps of the group 7 chromosomes were used to locatePer-A4 to a distal region of7AS. In addition, a further set of genes was identified as being active in root tissue. In wheat a single locus,Per-D5, was found on chromosome arm2DS. PMID- 24226348 TI - Expression of alcohol-soluble endosperm proteins in maize single and double mutants. AB - Many maize (Zea mays L.) mutant genes exist. Some affect protein content or composition, while others modify carbohydrates or kernel phenotype. In doublemutant lines, two mutant genes are present. We know little about interactions of such genes, however. We therefore examined a normal maize inbred, B37, 10 near-isogenic single mutants and 46 double mutants to analyze quantitative effects on alcohol-soluble endosperm proteins. Proteins were extracted with 70% ethanol0.5% sodium acetate-5% mercaptoethanol, and fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC). Early peaks were alcohol-soluble glutelin (ASG) subunits, while late peaks contained zein. Results were quantified and statistically analyzed. In many double mutants, protein compositions differed significantly from averages of compositions of corresponding single mutants. For example, a high-methionine, water-insoluble ASG is absent when the opaque-2 (o2) gene combines with shrunken 1 (sh1) or surgary-1 (su1). Another water-insoluble ASG nearly doubled when floury-2 (fl2) andsu1 combined. A high-proline, high-histidine, water-soluble ASG nearly doubled in combinations offl2 witho2,su1 and sugary-2 (su2). Zein was about half its expected value wheno2 combined with amylose-extender (ae), floury 1 (fl1), soft-starch (h),sh1 andsu1. Thus, rapid protein extraction and quantitative RP-HPLC showed major new epistatic and synergistic effects of several mutant genes on protein composition. Unexpectedly, these effects often involve genes that primarily affect starch composition or kernel phenotype. Alcohol-soluble proteins often vary in amount, as ino2 lines. They also differ in nutritional value. Thus, RP-HPLC analysis of these proteins can identify nutritionally superior genotypes, and may help explain the basis of such quality. PMID- 24226349 TI - Use of recombinant inbred lines of wheat for study of associations of high molecular-weight glutenin subunit alleles to quantitative traits : 1. Grain yield and quality prediction tests. AB - The high-molecular-weight glutenin subunits (HMW glutenin), encoded by alleles at homoeologous lociGlu-A1,Glu-B1, andGlu-D1 on the long arms of chromosomes1A,1B, and1D of a set of F8 random recombinant inbred lines (RIL) derived from the bread wheat cross Anza * Cajeme 71, were classified by SDS-PAGE. Anza has poor breadmaking quality and HMW-glutenin subunits (Payne numbers) null (Glu-A1c), 7+8 (Glu-B1b), and 2+12 (Glu-D1a); Cajeme 71 has good quality and 1 (Glu-A1a), 17+18 (Glu-B1i), and 5+10 (Glu-D1d). The combinations of these alleles in the RIL were examined for associations with grain yield and four indicators of grain quality - protein content, yellowberry, pearling index, and SDS sedimentation volume. Data were obtained from a field experiment with three nitrogen fertilization treatments on 48 RIL and the parents. Orthogonal partitioning of the genetic variance associated with the three HMW glutenin subunit loci into additive and epistatic (digenic and trigenic) effects showed strong associations of these loci with grain yield and the indicators of quality; however, the associations accounted for no more than 25% of the differences between the parents. Genetic variance was detected among the RIL, which had the same HMW glutenin genotype for all traits. Epistatic effects were absent for grain yield and yellowberry, but were substantial for grain protein content, pearling index, and SDS sedimentation volume. All three loci had large single-locus additive effects for grain yield, protein, and SDS sedimentation volume. Yellowberry was largely influenced byGlu B1 andGlu-D1, whereas pearling index was associated withGlu-A1 andGlu-B1. Even though the observed associations-of effects of HMW glutenin loci with the quantitative characters were small relative to the total genetic variability, they are of considerable importance in understanding the genetics of wheat quality, and are useful in the development of new wheat varieties with specific desired characteristics. PMID- 24226350 TI - Resistance toHeterodera avenue in the rye genome of triticale. AB - The cereal cyst nematode,Heterodera avenue Wollenweber, is a serious pest of cereals in many countries. A high level of resistance to the unique Australian pathotype of the nematode has been demonstrated in a triticale line (T701-4-6), which was originally obtained from CIMMYT. The level of resistance is similar to that in rye cultivar, South Australian, but higher than that in the wheat line (AUS 10894), hitherto reported to have useful resistance to the Australian pathotype. The gene for resistance was located on rye chromosome 6 (6R) after backcrossing the T701-4-6 line to wheat and correlating the resistance with the presence of individual rye chromosomes identified by morphological, cytological, and isozyme markers. Preliminary evidence suggests that the gene is located on the long arm of6R. To transfer the resistance to wheat, double monosomics of6R and6D in aph1bph1b homozygous background were selected from F2 progeny from a cross of disomic6R substitution for6D to theph1b mutant. Selfed seeds from these F2 plants will be screened for wheat-rye chromosome recombinants. PMID- 24226351 TI - Cotransformation frequencies of foreign genes in soybean cell cultures. AB - Through the use of electroporation and a soybean (Glycine max L.) protoplast system, we generated stably transformed cell lines expressing a number of foreign genes (neomycin phosphotransferase,beta-glucuronidase, chloramphenicol acetyl transferase, and phosphinothricin acetyl transferase). Selected and unselected marker genes were cointroduced either linked on a single plasmid or as separate plasmids. Calli expressing multiple genes were recovered, and Cotransformation frequencies were established for both cases. Our results show a 50% cotransformation frequency in the case of linked genes. In situations in which two genes are introduced on independent plasmids, cotransformation frequencies are 18%-27%. Similar rates of cotransformation were observed among various marker pairs. PMID- 24226352 TI - Stability of mitochondrial DNA in tissue-cultured cells of rice. AB - Restriction analysis of mitochondrial (mt) DNA from 3-month-old callus cultures of the cytoplasmic male sterile rice, V41A, which contains S2 or "wild abortive" cytoplasm, and its fertile maintainer, V41B, showed the same BamHI restriction profiles as mtDNA from the corresponding leaf material. Similarly, mtDNA of rice (var. Taipei 309) from leaves, a 2-month-old cell suspension (T3MS2/A), a totipotent suspension (T3MS) and a 19-month-old suspension, which had lost its protoplast regeneration ability (LB3), showed indistinguishable BamHI restriction profiles. However, clear differences in mtDNA restriction profiles were observed between LB3 and a 30-month-old suspension culture of Taipei 309 (LB1), which appeared to reflect substantial changes in the relative abundance of specific DNA sequences. Hybridisation of a maizecoxII gene probe to blots of restricted mtDNA confirmed that, while the relative abundance of certain mtDNA sequences was preserved during long-term tissue culture of rice, major changes in abundance were observed with other sequences. PMID- 24226353 TI - Linkage and cytogenetic maps of genes controlling endosperm storage proteins and isozymes in rye (Secale cereale L.). AB - An F1 plant fromSecale cereale ssp.ancestrale xtelocentric substitution lines3R of the cultivated rye "Petkus spring" was used as female in a cross with the inbred line Riodeva (I28), which has the standard chromosome arrangement. Single plants from this backcross progeny were analyzed for chromosome constitution, storage protein, and isozymic patterns. The seed protein loci were identified asSec-1a andSec-1b loci controlling 40-Kgamma-secalins andomega-secalins, respectively. These loci are located on the short arm of chromosome1R. TheSec-3 locus controlling high-molecular-weight secalins is located on the long arm of chromosome1R. A further seed protein locus,Pr-3 (55-K protein), was located on the short arm of chromosome1R. A linkage was found between the6Pgd-2 isozyme locus controlling 6-phosphogluconate dehydrogenase isozymes located on the long arm of chromosome1R and the four seed protein loci. The results favor the gene order:6Pgd-2 ...Sec-3 ... [centromere] ...Pr-3 ...Sec-1b ...Sec-1a. Other linkages detected werePer-3a andPer-3b (0.33+/-0.33 cM),Est-8 andEst-12 (0.33+/ 0.33 cM), andGot-3 and centromere (20.57+/-2.42 cM). The proxidase (Per), glutamate oxaloacetate transaminase (Got), and esterase (Est) loci were located on chromosome arms2RS,3RL, and6RL, respectively. The distances and the maps obtained are compared with data available in the literature. PMID- 24226354 TI - The effects of promoter on transient expression in conifer cell lines. AB - Protoplasts from suspension cultures of somatic embryos of white spruce (Picea glauca Moench Voss) were electroporated with plasmids containing the chimeric genes for chloramphenicol acetyl transferase (CAT) or beta-glucuronidase (GUS), under control of one of three promoters. Transient CAT gene expression of approximately equal magnitude resulted when the CAT gene was fused to either the cauliflower mosaic virus (CaMV) 35S promoter or the nopaline synthase (NOS) promoter. When the CAT gene was fused to a tandem repeat CaMV 35S promoter (pPBI 363), CAT enzyme activity compared to NOS or 35S promoters increased up to eightfold (cell line WS-34), and were up to 100-fold greater than control (electroporated without plasmid). Comparatively, protoplasts of black spruce (Picea mariana Mill) and jack pine (Pinus banksiana Lamb.), electroporated with pPBI-363, produced increases in CAT activity compared to control of 90-fold and 70-fold, respectively. White spruce (WS-34) protoplasts were subsequently electroporated with the GUS gene fused to the tandem repeat CaMV 35S promoter. Comparatively, GUS enzyme activity increased up to tenfold compared to GUS fused to a CaMV 35S promoter. The results indicated that transient expression of the CAT and GUS genes was influenced by the type of promoter and cell line used, as well as by electroporation conditions. PMID- 24226355 TI - Phylogeny of wild and cultivatedSolanum species based on nuclear restriction fragment length polymorphisms (RFLPs). AB - Phylogenetic relationships between 14 wild and 3 cultivatedSolanum species, including the European potato,Solanum tuberosum ssp.tuberosum, were inferred using DNA restriction fragment length polymorphisms (RFLPs) as discriminating characters. Phenetic trees were obtained based on distance matrices as well as on parsimony methods, which were not significantly altered either by the computational method used, or by the individual plant genotypes or RFLP markers chosen for the analysis. The reliability of the tree topologies was assessed and, as expected, it increased with the number of polymorphic restriction fragments scored. The individual genotypes within each species, the different species themselves, and the main branches of the trees were clearly separated from each other. The least reliable parts in the trees were the positions of closely related species within the main clusters.S. tuberosum spp.tuberosum formed one group closely related withS. tuberosum spp.andigena,S. stenotomum, andS. canasense. This was well separated from a second group formed byS. sparsipilum,berthaultii,kurtzianum,gourlayi,vernei,spegazzinii,chacoense, andmegistacrolobum. Two further branches were formed byS. demissum andS. acaule, and byS. polyadenium,S. pinnatisectum,S. stoloniferum, andS. etuberosum. The phenetic trees presented here supported the description of relationships amongSolanum species based on biosystematic studies, with the exception of the placement ofS. chacoense andS. megistacrolobum. PMID- 24226357 TI - Screening of rice (Oryza sativa L.) genotypes for physiological characters contributing to salinity resistance, and their relationship to overall performance. AB - Phenotypic resistance of salinity is expressed as the ability to survive and grow in a salinised medium. Some subjective measure of overall performance has normally been used in plant breeding programmes aimed at increasing salinity resistance, not only to evaluate progeny, but to select parents. Salinity resistance has, at least implicitly, been treated as a single trait. Physiological studies of rice suggest that a range of characteristics (such as low shoot sodium concentration, compartmentation of salt in older rather than younger leaves, tolerance to salt within leaves and plant vigour) would increase the ability of the plant to cope with salinity. We describe the screening of a large number of rice genotypes for overall performance (using an objective measure based on survival) and for the aforementioned physiological traits. There was wide variation in all the characters studied, but only vigour was strongly correlated with survival. Shoot sodium concentration, which a priori is expected to be important, accounted for only a small proportion of the variability in the survival of salinity. Tissue tolerance (the cellular component of resistance reflecting the ability to compartmentalise salt within leaves) revealed a fivefold range between genotypes in the tolerance of their leaves to salt, but this was not correlated positively with survival. On the basis of such (lack of) correlation, these traits would be rejected in normal plant breeding practice, but we discuss the fallacies involved in attempting correlation between individual traits and the overall performance of a salt-sensitive species in saline conditions. We conclude that whilst overall performance (survival) can be used to evaluate the salt resistance of a genotype, it is not the basis on which parents should be selected to construct a complex character through breeding. It was the norm for varieties which had one good characteristic affecting salt resistance to be unexceptional or poor in the others. This constitutes experimental evidence that the potential for salt resistance present in the rice genome has not been realised in genotypes currently extant. The results are discussed in relation to the use of physiological traits in plant breeding, with particular reference to environmental stresses that do not affect a significant part of a species' ecological range. PMID- 24226356 TI - The inheritance of beta-amylase null in storage roots of sweet potato,Ipomoea batatas (L.) Lam. AB - Several sweet potato genotypes were found to lack completely or to have only traces ofbeta-amylase in their storage roots. Such genotypes do not increase in sweetness during cooking because, without a sufficient amount ofbeta-amylase, the normal hydrolysis of starch to maltose does not occur in the cooking process. In order to study the inheritance of this biochemical variant in the genotype, 41 families were generated. The following conclusions were drawn from analyzing these families. (1) This trait is controlled by one recessive allele (designatedbeta-amy) (2) It is inherited in a hexasomic or tetradisomic manner, but not disomically or tetrasomically. This conclusion supports previous cytological data that sweet potato is an autohexaploid or has two identical genomes plus one genome which is somewhat different. (3) Thebeta-amy allele appears to exist at a high frequency in cultivated germplasm. (4) Breeding sweet potato for lowbeta-amylase activity is relatively easy. New types of sweet potato without normalbeta-amylase activity have great potential for processing and as a staple food. PMID- 24226358 TI - Transfer of Hessian fly resistance from 'Chaupon' rye to hexaploid wheat via a 2BS/2RL wheat-rye chromosome translocation. AB - Four wheat-rye lines derived from a cross between hexaploid wheat 'ND 7532' and 'Chaupon' rye were homogeneous for resistance to biotype L of the Hessian fly,Mayetiola destructor. Because the wheat parent was susceptible and the rye parent was resistant to larval feeding, resistance was derived from rye. Resistance of 'Chaupon' and the wheat-rye lines was expressed as larval antibiosis. First-instar larvae died after feeding on plants. Chromosomal analyses using C- and N-banding techniques were performed on plants of each line to identify genomes and structural changes of chromosomes. Results showed that two of the resistant lines were chromosome addition lines carrying either the complete rye chromosome,2R, or only the long arm of2R. The other two resistant lines were identified as being2BS/ 2RL wheat-rye translocation lines. It was concluded, therefore, that the long arm of rye chromosome2R carries a gene or gene complex that conditions antibiosis to Hessian fly larvae and, in the2BS/2RL translocation lines, this rye chromatin is cytologically stable and can be used directly in wheat breeding programs. PMID- 24226360 TI - Chromosome structure of durum wheat. AB - Meiotic pairing was analyzed at metaphase I in ABRR triticale * rye hybrids to identify the arm homoeology of chromosomes ofTriticum turgidum. Wheat chromosomes were identified using a C-banding technique. Results confirmed that the homoeologous relationships between chromosome arms of the A and B genomes inT. turgidum are the same as inT. aestivum, and that a double translocation involving4AL,5AL, and7BS is present inT. turgidum. It is proposed that a pericentric inversion involving a substantial portion of chromosome4A is present inT. turgidum andT. aestivum. PMID- 24226359 TI - Transfer of cytoplasm from newBeta CMS sources to sugar beet by asymmetric fusion : 1. Shoot regeneration from mesophyll protoplasts and characterization of regenerated plants. AB - For our program on the transfer of cytoplasmic male sterility (CMS) by cybridization inBeta vulgaris L. (sugar beet), we have developed a procedure for the isolation and culture of mesophyll protoplasts of sugar beet followed by shoot regeneration. A prerequisite proved to be the presence in the media of n propylgallate (nPG), a lipoxygenase inhibitor. Sustained divisions were found in all accessions that were tested. Plating efficiencies and regeneration ability varied greatly from one experiment to the other and appeared to be accession dependent. Shoots could be easily transferred to soil. A majority of the regenerants (72%) retained the diploid chromosome number. Somaclonar variation in phenotype was low (4.9%). Mitochondrial DNA probes, capable of discriminating different cytoplasms ofBeta spp. showed no rearrangements due to the protoplast and in vitro culture phase, indicating that these probes can be used to identify cybrids after asymmetric fusions. The data presented here open up possibilities for genetic engineering using protoplasts in one of the world's most important arable crops. PMID- 24226361 TI - Genetics of resistance toPuccinia graminis tritici andPuccinia recondite tritici in four South African wheats. AB - Genes for resistance toPuccinia graminis tritici andPuccinia recondita tritici identified in four South African wheats were:Sr6,Sr8a,Sr9e, andLr13 in 'W3762';Sr5,Sr8a,Sr9b,Sr12,Sr24,Lr13, andLr24 in 'W3760';Sr2,Sr24,SrC,Lr13, andLr24 in 'W3751'; andSr7a,Sr23,Sr36, andLr16 in 'W3755'. GenesSr2,Sr9e, andSr24 also conferred adult plant resistance to the predominant pathotypes ofP. graminis tritici. GenesSr7a,Sr23, andSrC, when present alone, did not confer acceptable adult plant resistance, even though low seedling reactions were associated with them when tested with the same pathotypes. Genetic recombination betweenLr13 andSr9e was estimated at 12.5%+/-2.3%. PMID- 24226362 TI - Deletion mutation as a means of isolating avirulence genes in flax rust. AB - The interaction between flax rust,Melampsora lini, and its host, flax,Linum usitatissimum, has been extensively studied, and certain genetic features make the system an appropriate choice to utilize in isolating genes conferring avirulence in rust. A mutant that was selected for virulence on Lx plants was isolated, after treatment with gamma rays, from a strain that is genotypicallyA L5,A-L6,A-L7,A-Lx/A-L5,A-L6,a-L7,a-Lx. These four specificities are tightly linked. Breeding tests showed that this mutant was genotypicallyA-L5,A-L6,a-L7,a Lx/a-L5,a-L6,a-L7,a-Lx and, when made homozygous for the mutant chromosome, was virulent onL5,L6,L7, andLx. This result excludes somatic recombination as a source of the mutation and indicates deletion as a likely cause. A 250 bp genomic sequence from a strain of rust homozygous for these four linked avirulence genes (A-L5,A-L6,A-L7,A-Lx) was isolated, using a method that allows the differential cloning of the specific DNA sequences located within a deletion in the mutant genome. This clone hybridized to two EcoRI bands in genomic DNA from the strain homozygous for the four linked avirulence genes and from the strain homozygousA L5 andA-L6 and heterozygousA-L7 andA-Lx, but showed no homology to DNA from the strain carrying the putative chromosomal deletion. The correlation between the genetically characterized deletion mutation and the isolation of a sequence from within a region of chromosome missing from this strain of rust suggests that this 250 bp tract may be part of, or closely linked to, the defined set of avirulence genes. PMID- 24226363 TI - Theoretical determination of the optimum number of parents for synthetics. AB - From the consideration of the expressions of the mean and of the variances amongk parent synthetics, it is possible, in the absence of epistasis, to give an algebraic determination of the optimum number of parents to include in a synthetic. The knowledge of four components of variance of inbred populations is necessary. Such components can be replaced by four simple statistics for the plant breeder: variances of general and specific combining abilities, variance among S1 families from the parents, and covariance between S1 value and general combining ability (GCA). A numerical study shows that this optimum is rather broad for a number of parents greater than four. As expected, the optimum tends to be higher for greater inbreeding depression. With inbreeding depression greater than 0.30, the maximum gain, in comparison to the random mating population with realistic selection intensity, would be less than 5%. In such a situation it will be better to use as synthetic the population improved by recurrent selection. PMID- 24226364 TI - Association between dwarfing genes 'Rht1' and 'Rht 2' and resistance toSeptoria tritici Blotch in winter wheat (Triticum aestivum L. em Thell). AB - Differences in levels of resistance toSeptoria tritici blotch were observed in plants with a specific height-reducing gene. When the gene 'Rht 2' was present either as an isoline or in the progeny, a higher degree of resistance was found. The most susceptible plants were observed in populations carrying the 'Rht 1' gene. Associations, as determined by phenotypic correlations, were detected betweenSeptoria tritici blotch and tall stature, late heading, and maturity. Plants having short stature, early heading, early maturity, and acceptable levels of resistance were identified in the F2 population whenRht 2 was present. Results of this study indicated that wheat breeders must select the appropriate dwarfing source that may confer resistance and grow large F2 populations, in order to increase the probability of obtaining desired genotypes. PMID- 24226365 TI - Quantitatively determined self-incompatibility : 2. Outcrossing inBorago officinaux. AB - It has been claimed that Borage (Borago officInalis L.) has a multifactorial self incompatibility system. Such systems may have a high level of ineffective pollination, and we show that this is the case in borage. The ranking of seed set from highest to lowest is as follows: bee-pollination; natural pollination in the absence of bees; artificial cross-pollination between unrelated plants; artificial cross-pollination between related plants; artificial self-pollination. In diallel crosses, significant parental effects were detected but no consistent patterns of seed set, which suggest a simple self-incompatibility system, were detected. The level of outcrossing with natural pollination was very variable but greater than 50%. Thus, there appears to be no straightforward self incompatibility system in borage. PMID- 24226366 TI - Intrinsic GUS-like activities in seed plants. AB - Fifty-two plant species, covering some Gymnosperms and all the key groups of Angiosperms, were chosen for surveying their intrinsic beta-glucuronidase-like activities. Histochemical (overnight incubation) and qualitative fluorometric (24 h incubation) assays indicated that, with few exceptions, such activities were detected in certain part(s) of the fruit walls, seed coats, endosperms or, especially, the embryos of the tested plants. Most of such activities in the excised immature embryos of soybean and string bean disappeared after one to a few days' in vitro culturing. Such activities in the intact mature seeds of these two species diminished also during germination process. The vegetative organs of seedlings/mature plants usually lack such activities. The enzyme(s) responsible for such activities was antigenically dissimilar to E. coli beta-glucuronidase. PMID- 24226367 TI - Induced expression of a chimeric gene construct in transgenic lettuce plants using tobacco pathogenesis-related protein gene promoter region. AB - The expression of a stress- and salicylic acidinducible protein gene from tobacco, PR1a protein gene, was determined after its Introduction to lettuce (Lactuca sativa L.) plants. The 5' flanking 2.4 Kb fragment from PR1a gene was joined to the bacterial beta -glucuronidase (GUS) gene (PR-GUS) and introduced into lettuce cotyledons by Agrobacterium-mediated gene transfer using a binary vector containing a kanamycin-resistance gene as a selectable marker. As a control with constitutive expression, the chimeric gene consisting of CaMV 35S RNA promoter and GUS gene (35S-GUS) was used. An improved method for shoot formation directly from lettuce cotyledons was used effectively for transformation, shortening the time for regeneration. In 70% or more of kanamycin resistant regenerated lettuce plants, into which PR-GUS or 35S-GUS was introduced, high GUS activity and integration of the chimeric gene into the lettuce genome were detected. By treatment with salicylic acid, GUS activity increased 3- to 50-fold in PR-GUS transformants, however, no increase was detected in 35S-GUS plants. These results showed that the promoter of the stress inducible tobacco PR1a protein gene was introduced into lettuce plants, and the introduced chimeric gene was expressed normally under the regulated control of the PRla promoter. PMID- 24226368 TI - Agrobacterium-mediated transformation of strawberry calli and recovery of transgenic plants. AB - Transformed calli and shoots of strawberry (Fragaria * ananassa Duch.) cv. Redcoat were obtained using Agrobacterium tumefaciens carrying plasmid pB1121. Inoculated leaf explants produced transgenic calli at a frequency of 3% on selection medium containing 50 MUg/ml kanamycin. Twenty per cent of selected caili regenerated, giving rise to transgenic shoots. All transgenic calli and shoots expressed substantial amounts of GUS and NPT-II activity. The Southern blot analysis confirmed the insertion of both marker genes into the strawberry genome as single and multiple copy inserts. The transgenic shoots elongated on rooting medium in the presence of 25 MUg/ml kanamycin, but exhibited reduced rooting ability. PMID- 24226369 TI - Embryo yield in wheat anther culture is influenced by the choice of sugar in the culture medium. AB - The effect of employing different sugars in wheat anther culture has been investigated using four Spring wheat cultivars. The most responsive cultivar, Orofen, gave a three to four-fold increase in embryo yield when maltose was used in place of sucrose, with 50 embryos being produced for every 100 anthers cultured. Measurement of sugar concentrations in the culture media indicated that sucrose was more rapidly hydrolysed than maltose. However, neither the osmotic potential of the medium nor the concentration of glucose appeared to be critical factors in determining embryo yield. PMID- 24226370 TI - Genotype- and promoter-induced variability in transient beta-glucuronidase expression in pea protoplasts. AB - Leaf mesophyll protoplasts isolated from pea (Pisum sativum L.) genotypes Century and PI244253 showed transient expression of beta-glucuronidase (GUS) when electroporated with plasmid DNA containing various promoter-leader sequence constructs driving the GUS gene. The optimum conditions for transient expression were: using protoplasts isolated from leaf material that had been kept in the dark for 90 h; electroporating at 250 V and 960 MUF; and using 125 MUg of calf thymus carrier DNA and 75 MU of plasmid DNA. PI244253 had 5 to 20 times the GUS activity levels of Century. Similar levels of transient expression were obtained using either the nopaline synthase or cauliflower mosaic virus 35S (35S) promoters. These levels were lower than that obtained using a duplicated 35S promoter derivative. The presence of an untranslated coat protein mRNA leader sequence from alfalfa mosaic virus between each promoter and the GUS gene resulted in increased GUS activity. Leaf mesophyll protoplasts and root protoplasts of PI244253 did not differ in levels of transient expression. PMID- 24226371 TI - Direct embryogenesis from single mesophyll protoplasts in alfalfa (Medicago sativa L.). AB - We used a tetraploid clone derived from an anther culture operation of 'Ladak' alfalfa to study the pathway of direct embryogenesis from leaf-mesophyll protoplasts. About 72% of the protoplasts divided, and 7% of those produced proembryos. Approximately 38% of the proembryos developed into green embryos, and 33% initiated calluses. Other proembryos dedifferentiated into calluses which later redifferentiated embryos. Sixteen percent of the embryos developed directly into plants, whereas 81% produced plants indirectly via secondary embryos. The remaining 3% of the primary embryos failed to develop into plants. The lowest plating efficiency for direct embryogenesis was 0.3%. The high percentage of direct embryogenesis observed was related to the genetic nature of the clone, low density of liquid medium, low protoplast culture density, and the composition of culture media. PMID- 24226372 TI - Transformation of eggplant (Solanum melongena L.) using a binary Agrobacterium tumefaciens vector. AB - Kanamycin resistant plants of Solarium melongena L. (eggplant) cv. Picentia were obtained following the cocultivation of leaf explants with Agrobacterium tumefaciens. A disarmed binary vector system containing the neomycin phosphotransferase (NPTII) gene as the selectable marker and chloramphenicol acetyltransferase (CAT) as a reporter gene was utilized. In vitro grown plants were used as sources of explants to produce transgenic plants on selective medium containing 100 mg/l kanamycin. The transformation and expression of the foreign genes was confirmed by DNA hybridizations, leaf disc assays, and by measuring NPTII and CAT enzyme activities. This technique is simple, rapid, efficient, and transgenic eggplants of this commercial cultivar have been transferred to soil where they have flowered and set seed. PMID- 24226373 TI - Cryopreservation of nucellar cells of navel orange (Citrus sinensis Osb. var. brasiliensis Tanaka) by vitrification. AB - The nucellar cells of navel orange(Citrus sinensis Osb. var. brasiliensis Tanaka) were successfully cryopreserved by vitrification. In this method, cells were sufficiently dehydrated with highly concentrated cryoprotective solution(PVS2) prior to direct plunge in liquid nitrogen. The PVS2 contains(w/v) 30% glycerol, 15% ethylene glycol and 15% DMSO in Murashige-Tucker medium(MT) containing 0.15 M sucrose. Cells were treated with 60% PVS2 at 25 degrees C for 5 min and then chilled PVS2 at 0 degrees C for 3 min. The cell suspension of about 0.1 ml was loaded in a 0.5 ml transparent plastic straw and directly plunged in liquid nitrogen for 30 min. After rapid warming, the cell suspension was expelled in 2 ml of MT medium containing 1.2 M sucrose. The average rate of survival was about 80%. The vitrified cells regenerated plantlets. This method is very simple and the time required for cryopreservation is only about 10 min. PMID- 24226374 TI - Somatic proembryo production from excised, wounded zygotic carrot embryos on hormone-free medium: evaluation of the effects of pH, ethylene and activated charcoal. AB - Wounded zygotic embryos of cultivated carrot produce somatic proembryos on hormone-free nutrient medium containing 1 mM NH 4 (+) as the sole nitrogen source. Continued maintenance of proembryos on this medium leads to a "pure" culture of preglobular stage proembryos (PGSPs). Ethylene had no effect on this process. Also, somatic embryo production was not affected by growing cultures on activated charcoal-impregnated filter papers. However, somatic proembryos initiated on activated charcoal papers were not maintainable as PGSPs and developed into later embryo stages. Normally, medium pH dropped from 5.7 to 4 during each subculture period, but when using activated charcoal papers the pH endpoint was around 6-7 due to a leachable substance(s) within the filter papers. When powdered, activated charcoal was used in the medium as an adsorbent of products potentially released after wounding, pH dropped at the normal rate and to the expected levels; proembryos did not mature into later embryo stages and were maintainable exclusively as PGSPs. Low pH (~ 4) is detrimental to proembryo production, but is essential to maintaining PGSPs on hormone-free nutrient medium, whereas a sustained pH >5.7 allows continued development of PGSPs into later embryo stages. PMID- 24226375 TI - Stress responses in alfalfa (Medicago sativa L.) III. Induction of medicarpin and cytochrome P450 enzyme activities in elicitor-treated cell suspension cultures and protoplasts. AB - Cell suspension cultures of alfalfa (Medicago sativa L.) accumulated phenolic secondary metabolites in a pattern similar to that seen in alfalfa roots. Upon treatment with a crude elicitor preparation from the bean pathogen Colletotrichum lindemuthianum, the pterocarpan phytoalexin medicarpin accumulated in cells and culture medium. The extractable activities of six enzymes involved in medicarpin biosynthesis (including three cytochrome P450 activities) were induced by treatment with elicitor, and their induction kinetics correlated with the rate of medicarpin accumulation. However, protoplasts prepared from these cultures accumulated neither medicarpin nor other secondary products after treatment with elicitor. The cytochrome P450 activities were induced during the preparation of the protoplasts, but could be further induced by treatment with fungal elicitor. The results are discussed in relation to the use of alfalfa protoplasts as a system for functional analysis of cloned defense genes. PMID- 24226376 TI - Stress responses in alfalfa (Medicago sativa L.) IV. Expression of defense gene constructs in electroporated suspension cell protoplasts. AB - We have investigated conditions for the uptake and expression of chimeric genes in protoplasts of alfalfa (Medicago sativa L.). Constructs containing the bacterial reporter gene chloramphenicol acetyltransferase (CAT) under the control of either the cauliflower mosaic virus 35S promoter or a bean chalcone synthase (CHS) promoter were introduced into protoplasts by electroporation in the presence of polyethyleneglycol. The extent of expression in the absence of added inducers depended on the conditions for isolation, electroporation and subsequent culture of the protoplasts. Expression of the CHS promoter construct was increased on exposure of the protoplasts to a fungal elicitor or reduced glutathione. The relative levels of induced expression in relation to either basal expression or the type of elicitor used depended on the age of the suspension cultures from which the protoplasts were isolated. Electroporation of protoplasts with a construct from which bean CHS antisense transcripts were synthesized under the control of the 35S promoter resulted in the inhibition of appearance of elicitor-induced endogenous alfalfa CHS activity. The suitability of the alfalfa protoplast system for analysis and potential identification of defense response genes is discussed. PMID- 24226377 TI - Production of isolated somatic embryos from sunflower thin cell layers. AB - We describe here a two step procedure which allows the easy isolation of somatic embryos from Sunflower (Helianthus annuus L.) hypocotyl tissues. Thin cell layers composed of the epidermis plus 3 to 6 parenchyma cell layers were incubated for 5 days in a basal Murashige and Skoog medium using an auxin to cytokinin weight ratio of 1/1. The epidermis layers were then transferred to a Gamborg medium containing a high level of sucrose. After one week of incubation in this medium, many somatic embryos started to be released from the parental epidermal tissue. Even though the germination of these embryos is difficult, we have been able to induce secondary embryos and regenerate fertile plants. PMID- 24226378 TI - Regeneration of fertile plants from embryogenic suspension culture protoplasts of Sorghum vulgare. AB - Protoplasts were isolated from immature inflorescence-derived embryogenic suspension cultures of two cultivars of Sorghum vulgare. The protoplasts were cultured in a modified K8P liquid medium. They started to divide after 4-5 days of culture, and achieved 16.8% division frequency by 10 days. Protocalli proliferated further upon transfer to C1 solid medium. After that, they were moved to C1 differentiation medium to induce shoot formation, followed by whole plant regeneration. So far, 60 plants have been obtained, with only two albinos. Some of these have been transplanted to soil in pots and grown to flowering and have set seeds. PMID- 24226379 TI - Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease. AB - Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves. PMID- 24226380 TI - Elusive diagnosis of left ear nodules. Cutaneous Rosai-Dorfman disease (RDD). PMID- 24226382 TI - Enantioselective organocatalytic oxidative enamine catalysis-1,5-hydride transfer cyclization sequences: asymmetric synthesis of tetrahydroquinolines. AB - The first organocatalytic enantioselective intramolecular oxidative enamine catalysis and 1,5-hydride transfer-ring closure reaction cascade is described. This neutral reaction cascade allows for the efficient formation of ring-fused tetrahydroquinolines with high enantioselectivities. PMID- 24226381 TI - Prophylaxis of intra- and postoperative nausea and vomiting in patients during cesarean section in spinal anesthesia. AB - BACKGROUND: This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable anti-emetic strategy for these patients. MATERIAL AND METHODS: Spinal anesthesia was performed in left prone position, at L3/L4 with hyperbaric 0.5% Bupivacaine according to a cc/cm body height ratio. There were no opioids given peri-operatively. The patients received either no prophylaxis (Group I) or tropisetron and metoclopramide (Group II) or dimenhydrinate and dexamethasone (Group III), or tropisetron as a single medication (Group IV). The primary outcome was nausea and/or vomiting (NV) in the intraoperative, early (0-2 h) or late (2-24 h) postoperative period. Multivariate statistical analysis was conducted with a regression analysis and a backward elimination of factors without significant correlation. RESULTS: All prophylactic agents significantly reduced NV incidence intraoperatively. Relative risk reduction for NV by prophylaxis was most effective (59.5%) in Group II (tropisetron and metoclopramide). In Group III (dimenhydrinate and dexamethasone), NV risk was reduced by 29.9% and by 28.7% in Group IV (tropisetron mono-therapy). The incidence of NV in the early (0?2 h) and the late (2?24 h) postoperative period was low all over (7.8%), but the relative risk reduction of NV in the early postoperative period was 54.1% (Group IV), 45.1% (Group III), and 34.8% (Group II), respectively. In the late postoperative period, there was no significant difference between the 4 groups. CONCLUSIONS: We recommend a prophylactic medication with tropisetron 2 mg and metoclopramide 20 mg for patients during caesarean section. These agents are safe, reasonably priced, and highly efficient in preventing nausea and vomiting. PMID- 24226383 TI - Progestin-only pills for contraception. AB - BACKGROUND: The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined oral contraceptives containing an estrogen plus progestin, these pills contain only a progestin (progestogen) and are taken without interruption. How these pills compare to others in their class or to combined oral contraceptives is not clear. OBJECTIVES: This review examined randomized controlled trials of progestin-only pills for differences in efficacy, acceptability, and continuation rates. SEARCH METHODS: Through October 2013, we searched the computerized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, and LILACS for studies of progestin-only pills. We also searched for current trials via ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE. SELECTION CRITERIA: We included all randomized controlled trials in any language that included progestin-only pills for contraception. We incorporated any comparison with a progestin-only pill; this could include different doses, other progestin-only pills, combined oral contraceptives, or other contraceptives. DATA COLLECTION AND ANALYSIS: The first author abstracted the data and entered the information into RevMan 5. Another author performed a second, independent data abstraction to verify the initial data entry.We attempted to extract life-table rates (actuarial or continuous) and used the rate difference as the effect measure. Where life-table rates were not published, we used the incidence rate ratio (ratio of Pearl rates). Where only the crude number of events was published, we calculated the Peto odds ratio with 95% confidence interval (CI) using a fixed-effect model. For continuous variables, the mean difference (MD) was computed with 95% CI. Because of disparate exposures, we were not able to combine studies in meta-analysis. MAIN RESULTS: Six trials met the inclusion criteria. We have not found any new studies since the initial review. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin only pill containing levonorgestrel 30 MUg had higher efficacy than did the pill containing norethisterone 350 MUg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial. AUTHORS' CONCLUSIONS: Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives. PMID- 24226384 TI - Improved mass accuracy in matrix-assisted laser desorption/ionization time-of flight mass spectrometry of peptides. AB - One problem of matrix-assisted laser desorption ionization coupled to time-of flight mass spectrometry is the moderate mass accuracy that typically can be obtained in routine applications, Here we report improved mass accuracy for peptides, even when low amounts and complex peptide mixtures are used. A new procedure for preparing matrix surfaces is used, and there is no need to mix the matrix with the sample or to add internal standards. Examples are shown with a mass accuracy better than 50 ppm in a peptide mixture. Peptide mapping as well as sequencing by creating "ragged ends" or "ladder sequencing" should benefit especially from the improved mass accuracy. PMID- 24226385 TI - Interaction of angiotensin peptides and zinc metal ions probed by electrospray ionization mass spectrometry. AB - Electrospray ionization-tandem mass spectrometry experiments were used to provide evidence regarding the sites of interactions between zinc metal ions and angiotensin peptides. The electrospray ionization mass spectra of histidine containing human angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) and angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) in the presence of zinc show abundant multiply charged ions for the zinc-attached peptide [M + aZn(2+) +(c - 2a)H(+)](c+), where a = 1, 2 and c is charge. From collisionally activated dissociation experiments, with both low energy (triple quadrupole mass spectrometry) and high energy collisions (linked scan at constant B/E with a double focusing instrument) of the [M + Zn](2+) and [M + Zn + H](3+) ions for angiotensin II, a [b 6 + Zn](2+) species is produced as the most abundant product ion, suggesting that the zinc interaction site is in the vicinity of the His(6) residue. Additionally, tandem mass spectra from the zinc-attached ions for angiotensin I show abundant [b 6 + Zn](2+) and [b 9 + Zn](2+) products, providing evidence that both His(6) and His(9) are involved in zinc coordination. PMID- 24226386 TI - The effect of charge state and the localization of charge on the collision induced dissociation of peptide ions. AB - The effect that charge state has on the collision-induced dissociation (CID) of peptide ions is examined in detail for several representative peptides under high energy collision conditions. The CID spectra of singly and doubly charged precursor ions (generated by fast-atom bombardment and electrospray ionization, respectively) are compared for several peptides with similar primary structure. It is shown that for peptides that contain highly basic amino acids, the dissociation of doubly charged ions is strongly influenced by the position of these residues within the peptide and the general observations reported concerning the dissociation of singly charged ions can be extended to precursors with higher charge states. Based on the dissociation behavior of the doubly charged ions of these peptides, it is demonstrated that two charges can reside in close proximity in the precursor ions, overcoming possible repulsion effects, when favored by a high concentration of basic sites. In addition)' this work illustrates that in the case of doubly charged ions..the charge state of some fragment ions can be determined directly from the mass-to-charge ratio assignments of the CID spectrum. PMID- 24226387 TI - An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. AB - A method to correlate the uninterpreted tandem mass spectra of peptides produced under low energy (10-50 eV) collision conditions with amino acid sequences in the Genpept database has been developed. In this method the protein database is searched to identify linear amino acid sequences within a mass tolerance of +/-1 u of the precursor ion molecular weight A cross-correlation function is then used to provide a measurement of similarity between the mass-to-charge ratios for the fragment ions predicted from amino acid sequences obtained from the database and the fragment ions observed in the tandem mass spectrum. In general, a difference greater than 0.1 between the normalized cross-correlation functions of the first- and second-ranked search results indicates a successful match between sequence and spectrum. Searches of species-specific protein databases with tandem mass spectra acquired from peptides obtained from the enzymatically digested total proteins of E. coli and S. cerevisiae cells allowed matching of the spectra to amino acid sequences within proteins of these organisms. The approach described in this manuscript provides a convenient method to interpret tandem mass spectra with known sequences in a protein database. PMID- 24226388 TI - Gas-Phase reactions of O 2 (-.) with alkyl and aryl esters of benzenedicarboxylic acids. AB - The reactions of O 2 (-.) with alkyl and aryl esters of benzenedicarboxylic acids have been studied under negative-ion chemical ionization (NICI) conditions via a conventional chemical ionization source. Reaction mechanisms have been elucidated by using ion isolation techniques on a Fourier transform ion cyclotron resonance mass spectrometer. In addition, (18)O 2 (-.) has been used as the reagent and the products of competitive reactions that involve the mixed esters of benzenedicarboxylic acids have been studied. O 2 (-.) reactions with the alkyl esters of 1,2- and l,3-benzenedicarboxylic acids are attributed to SN2 displacement at the O-alkyl carbon. The spectra of mixed alkyl esters show that O 2 (-.) attack is reduced at sterically hindered alkyl groups. In contrast with the spectra of 1,2- and l,3-benzenedicarboxylic acids, the spectra of 1,4 benzenedicarboxylic acids are dominated by M(-.) production. Reactions of O 2 ( .) with phenyl benzoates and the aryl esters of benzenedicarboxylic acids proceed via addition-elimination pathways. Experiments with mixed alkyl-aryl benzenedicarboxylic acid esters show that the addition-elimination reaction pathway is preferred over O-alkyl SN2 displacement. The O2/ Ar-NICI mass spectra show features that can be used to distinguish 1,2-, 1,3-, and 1/4 benzenedicarboxylic acid esters. Molecular and fragment ions provide structural information complementary to that generated under electron ionization and chemical ionization conditions. PMID- 24226389 TI - Automated high-speed analysis of selected organic compounds in urban air by on line isotopic dilution cryofocusing gas chromatography/mass spectrometry. AB - An automated environmental air monitor has been developed to measure selected organic compounds in urban air. The instrument is based on a cryofocusing-thermal desorption gas chromatographic mass spectrometry technique where the mass spectrometer is a slightly modified residual gas analyzer (RGA). The RGA was chosen as a detector because the whole system must be robust for long periods, with 24-h continuous air monitoring. RCA are extremely simple and seemed the most reliable mass spectrometers for this purpose. Moreover, because they have no physically limited ion source, contamination is considerably reduced, so maintenance intervals are longer.The gas chromatograph is equipped with a computer-controlled six-way sampling valve, with a 100-mL sampling loop and thermal desorption cold trap injector. Environmental air is enriched with an isotopically labeled internal standard in the sampling line. This internal standard is added with a validated, custom-made, permeation tube device. The "on line" internal standard provides for high quality quantitative data because all variations in instrument sensitivity in cryofocusing or in thermal desorption efficiency are taken into account. High repetition rates (down to 5 min for a full analytical cycle) are obtained with the use of an isothermal gas chromatography program, microbore capillary column, and environmental air sampling during the gas chromatography run. PMID- 24226390 TI - An inductively coupled plasma-time-of-flight mass spectrometer for elemental analysis. Part I: Optimization and characteristics. AB - An inductively coupled plasma-time-of-flight mass spectrometer (ICP-TOFMS) has been constructed and evaluated for elemental analysis. The instrument produces analog spectra similar to those from quadrupole inductively coupled plasma mass spectrometers. The large abundance of Ar ions is deflected away from the microchannel plate detector to reduce detector dead time and space-charge complications. The ICP-TOFMS, operated in a linear (nonreflecting) mode, currently has a resolving power of 500 (full width at half maximum). Present ion optics employed in the instrument require a trade-off between signal-to-noise ratio and resolving power. In addition, mass-dependent kinetic energies in the supersonic beam created in the ICP mass spectrometer interface cause a mass bias in the right-angle TOFMS because the ions must be steered to the detector to compensate for their velocity in the supersonic beam direction. In the current design the sampling duty cycle is only approximately 3%, thereby limiting sensitivity. However, positive potentials applied to the right-angle extraction region can increase sensitivity by a factor of 2-4 by slowing down the ions that enter the extraction zone. The transmission efficiency of the TOFMS is approximately 20% and is limited by divergence of the ion packet in the drift tube. PMID- 24226391 TI - Beam-induced reaction between meta-nitrobenzyl alcohol and dipyridocyanine dyes in liquid-secondary-ion mass spectrometry. AB - Analyses of cationic dipyridocyanine dyes by liquid-secondary-ion mass spectrometry in a liquid matrix of meta-nitrobenzyl alcohol (rnNBA) provide evidence for beam-induced addition reactions between the sample molecule (C) and the mNBA solvent. The ionic products of these addition reactions formally correspond to [C+mNBA-O2](+), Ic+mNBA-O2-H](+), and [C+mNBA-O2-2H](+). Initial loss of H from the adduct ion extends the conjugation of the adduct into the mNBA ring structure, whereas the final loss of hydrogen is thought to be promulgated by the formation of a benzylic radical stabilized through resonance with the pi electron system of the nitrobenzyl alcohol. Alternatively, two hydrogens may be lost from the alcohol functionality to form an aldehyde. PMID- 24226392 TI - Matrix design for matrix-assisted laser desorption ionization: Sensitive determination of PAH-DNA adducts. AB - Two matrices, 4-phenyl-alpha-eyanocinnamic acid (PCC) and 4-benzyloxy-alpha eyanocinnamic acid (BCC), were identified for the determination of polycyclic aromatic hydrocarbon (PAH) adducts of DNA bases by matrix-assisted laser desorption ionization. These matrices were designed based on the concept that the matrix and the analyte should have structural similarities. PCC is a good matrix for the desorption of not only PAH-modified DNA bases, but also PAHs themselves and their metabolites. Detections can be made at the femtomolar level. PMID- 24226393 TI - Erratum to: Atmospheric pressure chemical ionization of alkanes, alkenes, and cydoalkanes. PMID- 24226395 TI - Isolation of monoclonal antibodies reacting with peribacteriod membranes and other components of pea root nodules containing Rhizobium leguminosarum. AB - Plant and bacterial antigens contributing to nodule development and symbiosis in pea (Pisum sativum L.) roots were identified after isolation of a set of monoclonal antibody (McAb)-producing hybridoma lines. Rats were immunised with the peribacteriod material released by mild osmotic shock treatment from membrane enclosed bacteroids of Rhizobium leguminosarum bv. viceae. In order to diversify the range of McAb specificities, this material was either used as immunogen directly (method 1), or after immunodepletion of a set of glycoprotein and lipopolysaccharide antigens (method 2), or after deglycosylation (method 3). After fusion and screening of cloned hybridoma lines, these three immunisation methods gave respectively 4, 2 and 1 classes of McAb with unique antigen specificities. Ultrastructural immunogold localisation studies showed four different antigens to be present on peribacteriod and plasma membranes (identified by MAC 64, 202, 206 or 209); in addition, a glycoprotein of plant origin but present in the infection-thread matrix was identified by MAC 204. Although none of the epitopes recognised by these McAb was nodule-specific, several were found to be more abundant in extracts of nodule tissue than in uninfected roots (MAC 64, 202, 204, 206). Two McAb reacted with new bacterial antigens: MAC 203 identified a bacterial antigen expressed upon infection but not in free-living cultures of Rhizobium, and MAC 115 identified a bacterial polypeptide (55 kdaltons) that was present in both free-living and bacteroid forms. There were also some McAb of broader specificity that react with antigens present in both plant and bacterial cytoplasms. PMID- 24226396 TI - Growth of anthers in Lilium longiflorum : A kinematic analysis. AB - The post-initiation growth of 64 anthers (1.1-17.4 mm long) in Lilium longiflorum Thumb. was examined by time-lapse marking experiments in combination with serial sections and the scanning electron microscope. Each anther was characterized by spatial and temporal variation in growth rate. Larger anthers had two, and occasionally three, series of peaks and troughs in local growth rate. Regions of negative growth rate were frequently encountered. When observed over several days, the growth maxima and minima were found to move basipetally as a waveform down the length of the anther. The wavelength was longer in taller anthers; amplitude and frequency were variable, and anthers of the same size were not always synchronous. Distribution patterns of cell division (and elongation, once division has ceased) recapitulate the growth data. Anther growth is a non-steady system, therefore, with growth centers constantly shifting. Implications for future studies in organ growth patterns are discussed. PMID- 24226397 TI - The capacity of plastids from developing pea cotyledons to synthesise acetyl CoA. AB - In order to determine whether the enzymes required to convert triose phosphate to acetyl CoA were present in pea (Pisum sativum L.) seed plastids, a rapid, mechanical technique was used to isolate plastids from developing cotyledons. The plastids were intact and the extraplastidial contamination was low. The following glycolytic enzymes, though predominantly cytosolic, were found to be present in plastids: glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12), phosphoglycerate kinase (EC 2.7.2.3), and pyruvate kinase(EC 2.7.1.40). Evidence is presented which indicates that plastids also contained low activities of enolase (EC 4.2.1.11) and phosphoglycerate mutase (EC 2.7.5.3). Pyruvate dehydrogenase, although predominantly mitochondrial, was also present in plastids. The plastidial activities of the above enzymes were high enough to account for the rate of lipid synthesis observed in vivo. PMID- 24226398 TI - Leaf anatomy and ultrastructure of the Crassulacean-acid-metabolism plant Kalanchoe daigremontiana. AB - Light-microscopic analysis of leaf clearings of the obligate Crassulacean-acid metabolism (CAM) species Kalanchoe daigremontiana Hamet et Perr. has shown the existence of unusual and highly irregular venation patterns. Fifth-order veins exhibit a three-dimensional random orientation with respect to the mesophyll. Minor veins were often observed crossing over or under each other and over and under major veins in the mesophyll. Paraffin sections of mature leaves show tannin cells scattered throughout the mesophyll rather evenly spaced, and a distinct layer of tannin cells below the abaxial epidermis. Scanning electron microscopy showed that bundle-sheath cells are distinct from the surrounding mesophyll in veins of all orders. Transmission electron microscopy demonstrated developing sieve-tube elements in expanded leaves. Cytosolic vesicles produced by dictyosomes undergo a diurnal variation in number and were often observed in association with the chloroplasts. These vesicles are an interesting feature of cell ultrastructure of CAM cells and may serve a regulatory role in the diurnal malic-acid fluctuations in this species. PMID- 24226399 TI - Plasmalemma- and tonoplast-ATPase activity in mesophyll protoplasts, vacuoles and microsomes of the Crassulacean-acid-metabolism plant Kalanchoe daigremontiana. AB - Adenosine-triphosphatase activity on the plasmalemma and tonoplast of isolated mesophyll protoplasts, isolated vacuoles and tonoplast-derived microsomes of the Crassulacean-acid-metabolism plant Kalanchoe daigremontiana Hamet et Perr., was localized by a cytochemical procedure using lead citrate. Enzyme activity was detected on the cytoplasmic surfaces of the plasmalemma and tonoplast. The identity of the enzymes was confirmed by various treatments differentiating the enzymes by their sensitivity to inhibitors of plasmalemma and tonoplast H(+) ATPase. Isolated vacuoles and microsomes prepared from isolated vacuoles clearly exhibited single-sided deposition on membrane surfaces. PMID- 24226400 TI - Cellular localization of nonhost resistance reactions of parsley (Petroselinum crispum) to fungal infection. AB - The response of parsley seedlings (Petroselinum crispum) inoculated with zoospores of the soybean-pathogenic fungus, Phytophthora megasperma f. sp. glycinea, ranged from "immunity" to "physiological susceptibility" depending on the post-inoculation environmental conditions. Typical nonhost resistance reactions, hypersensitive cell death and the formation of small local lesions, occurred under high relative humidity and 16 h illumination per day. Localized biochemical reactions were monitored using fluorescence microscopy combined with histochemical and immunohistochemical methods. The rapid accumulation of furanocoumarin phytoalexins, wall-bound phenolics and callose was detected around infection sites. Indirect antibody staining of frozen tissue sections demonstrated the local accumulation of phenylalanine ammonia-lyase, a key enzyme of general phenylpropanoid metabolism, and S-adenosyl-L-methionine: bergaptol O methyltransferase, a specific enzyme of the furanocoumarin pathway. The results indicate that phenylpropanoid derivatives are synthesized de novo at infection sites. PMID- 24226401 TI - Influence of energy flux and quality of light on the molecular organization of the photosynthetic apparatus in Scenedesmus. AB - The photosynthetic apparatus of the unicellular green alga Scenedesmus obliquus adapts to different levels and qualities of light as documented by the fluence rate curves of photosynthetic oxygen evolution. Cultures adapted to low fluence rates of white light (5W.m(-2)) have more chlorophyll (Chl) per cell mass, a higher chlorophyll to carotenoid ratio and a doubling of the chlorophyll to cytochrome f ratio compared with cells adapted to high fluence rates of white light (20W.m(-2)). Only small differences can be observed in the halfrise time of fluorescence induction, the electrophoretic profile of the pigment-protein complexes and the Chl a/Chl b-ratio. Scenedesmus cells adapted to blue light of high spectral purity demonstrate, in comparison with those adapted to red light, a higher chlorophyll content, a higher ratio of chlorophyll to carotenoid and a much higher ratio of chlorophyll to cytochrome f. Regarding these parameters and the fluence-rate curves of photosynthesis, the blue light causes the same effects as low levels of white light. In contrast, the action of red light resembles rather that of high levels of white light. Blue-light-adapted Scenedesmus cells have a smaller Chl a to Chl b ratio, a faster half-rise time of fluorescence induction and more chlorophyll in the light-harvesting system than red-light adapted cells, as shown in the electrophoretic profile of the pigment-protein complexes. Based on these results we propose a model for the adaptation of the photosynthetic apparatus of Scenedesmus to different levels and qualities of light. In this model low as compared with high levels of white light result in an increase in the number of photosystems per electron-transport chain, but not in an increase in the size of these photosystems. The same result is obtained by adaptation to blue light. The lack of sufficient Chl b formation in red-light adapted cells results in a decrease in the light harvesting chlorophyll-protein complexes and a photosynthetic response like that found in cells adapted to high light levels. The findings reported here confirm our earlier results in comparing blue-and red-light adaptation of the photosynthetic apparatus with adaptation to low and high levels of white light, respectively. PMID- 24226402 TI - Purification and characterization of D-glycerate-3-kinase from maize leaves. AB - Glycerate kinase (GK; EC 2.7.1.31) from maize (Zea mays L.) leaves was purified by a sequence of ammonium-sulfate precipitations and chromatography on diethylaminoethyl-cellulose, hydroxyapatite, Sephadex G-75SF and dye ligand (Green A) columns. The purest preparation was almost 1300-fold enriched and had a specific activity of 68 MUmol . min(-1) . (mg protein) (-1). The enzyme was a monomer of a relative molecular mass (Mr) of 44 kDa (kdalton) as determined by gel filtration, electrophoresis in dissociating conditions and by immunoblots. The enzyme was only weakly recognized by polyclonal antibodies against purified spinach GK, indicating substantial differences in molecular structure of the two proteins. Highly reducing conditions stabilized GK activity and were required for activation of crude leaf enzyme. The enzyme had a broad pH optimum of 6.8-8.5, and formed 3-phosphoglycerate and ADP as reaction products. Apparent K ms for D glycerate and Mg-ATP were 0.11 and 0.25 mM, respectively. The enzyme was strongly affected by a number of phosphoesters, especially by 3-phosphoglycerate (K i= 0.36 mM), fructose bisphosphates and nucleoside bisphosphates. Inhibition by 3 phosphoglycerate was competitive to Mg-ATP and noncompetitive to D-glycerate. Pyruvate was found noncompetitive to D-glycerate (K is=4 mM). The ratio of stromal concentration of Mg-ATP to phosphoesters, particularly to 3 phosphoglycerate, may be of importance in the regulation of GK during C4 photosynthesis. PMID- 24226403 TI - Sulfur-dioxide fluxes into different cellular compartments of leaves photosynthesizing in a polluted atmosphere : I. Computer analysis. AB - Using experimental information obtained in earlier studies on cellular buffering and SO2 uptake into leaves (Pfanz and Heber, 1986, Plant Physiol. 81, 597-602; Pfanz et al., 1987 a, b, Plant Physiol.), a mathematical model is presented which permits computer analysis of the transport of SO2 from the atmosphere into the mesophyll of leaves and describes the intracellular distribution of hydration products of SO2. Oxidation of sulfite and metabolization of sulfate can also be included. Although the model does not attempt to incorporate all available information on the intracellular transport of sulfur species, it permits general conclusions in regard to cellular responses to SO2. The model can be extended and modified for gases other than SO2. Examples are presented to illustrate the information the model is able to give. Times required for SO2 equilibration are long. Equilibrium relationships between SO2 in the atmosphere and cellular SO2 show that in order to survive in even slightly contaminated air, leaves must prevent equilibration between external and internal SO2. PMID- 24226404 TI - Sulfur-dioxide fluxes into different cellular compartments of leaves photosynthesizing in a polluted atmosphere : II. Consequences of SO2 uptake as revealed by computer analysis. AB - A computer model is used to analyze fluxes of SO2 from polluted air into leaves and the intracellular distribution of sulfur species derived from SO2. The analysis considers only effects of acidification and of anion accumulation. (i) The SO2 flux into leaves is practically exclusively controlled by the boundary layer resistance of leaves to gas diffusion and by stomatal opening. At constant stomatal opening, flux is proportional to the concentration of SO2 in air. (ii) The sink capacity of cellular compartments for SO2 depends on intracellular pH and the intracellular localization of reactions capable of oxidizing or reducing SO2. In the mesophyll of illuminated leaves, the chloroplasts possess the highest trapping potential for SO2. (iii) If intracellular ion transport were insignificant, and if bisulfite and sulfite could not be oxidized or reduced, leaves with opened stomata would rapidly be killed both by the accumulation of sulfites and by acidification of chloroplasts and cytosol even if SO2 levels in air did not exceed concentrations thought to be permissible. Acidification and sulfite accumulation would remain confined largely to the chloroplasts and to the cytosol under these conditions. (iv) Transport of bisulfite and protons produced by hydration of SO2 into the vacuole cannot solve the problem of cytoplasmic accumulation of bisulfite and sulfite and of cytoplasmic acidification, because SO2 generated in the acidic vacuole from the bisulfite anion would diffuse back into the cytoplasm. (v) Oxidation to sulfate which is known to occur mainly in the chloroplasts can solve the problem of cytoplasmic sulfite and bisulfite accumulation, but aggravates the problem of chloroplastic and cytosolic acidification. (vi) A temporary solution to the problem of acidification requires the transfer of H(+) and sulfate into the vacuole. This transport needs to be energized. The storage capacity of the vacuole for protons and sulfate defines the extent to which SO2 can be detoxified by oxidation and removal of the resulting protons and sulfate anions from the cytoplasm. Calculations show that even at atmospheric levels of SO2 thought to be tolerable, known vacuolar buffer capacities are insufficient to cope with proton production during oxidation of SO2 to sulfate within a vegetation period. (vii) A permanent solution to the problem of acidification is the removal of protons. Protons are consumed during the reduction of sulfate to sulfide. Proteins and peptides contain sulfur at the level of sulfide. During photosynthesis in the presence of the permissible concentration of 0.05MUl.l(-1) SO2, sulfur may be deposited in plants at a ratio not far from 1/500 in relation to carbon. The content of reduced sulfur to carbon is similar to that ratio only in fast-growing, protein-rich plants. Such plants may experience little difficulty in detoxifying SO2. In contrast, many trees may contain reduced sulfur at a ratio as low as 1/10 000 in relation to carbon. Excess sulfur deposited in such trees during photosynthesis in polluted air gives rise to sulfate and protons. If detoxification of SO2 by reduction is inadequate, and if the storage capacity of the vacuoles for protons and sulfate is exhausted, damage is unavoidable. Calculations indicate that trees with a low ratio of reduced S to C cannot tolerate long-term exposure to concentrations of SO2 as low as 0.02 or 0.03 MUl.l(-1) which so far have been considered to be non-toxic to sensitive plant species. PMID- 24226405 TI - Calcium requirement in nitrogen fixation in the cyanobacterium Synechococcus RF 1. AB - Under diurnal 16/8-h light-dark cycles, ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) at 1 mM completely blocked the appearance of rhythmic N2-fixing activity in Synechococcus RF-1. Ca(2+) at 2 mM, when supplied either together with or several hours after the EGTA application, restored the nitrogenase activity, whereas, when Ca(2+) was supplied several hours later, the peak of nitrogenase activity was shifted from the dark to the light period in which the activity is normally suppressed. Sr(2+) also reversed the inhibition by EGTA, but only partially. When O2 in the gas phase above the culture was below 1%, the inhibition of nitrogenase activity by EGTA was reduced to less than 20% of the control value without EGTA. Thus Ca(2+) appears to be required by the cell to protect its nitrogenase from inactivation by O2. In media without EGTA, a close correlation between nitrogenase activity and concentrations of Ca(2+) was also observed. PMID- 24226406 TI - Effect of light and gibberellic acid on cell division in the first foliage leaf of durum wheat (Triticum durum Desf.). AB - The present paper is part of a research program which aims at a quantitative analysis of the effects of light and gibberellic acid (GA3) on growth of the first foliage leaf in durum wheat (Triticum durum Desf.). Since leaf growth is the combined result of the increase in cell number (cell division) and cell enlargement, the influence of light and GA3 treatment on cell division in the basal meristem of the first leaf in two cultivars, Cappelli and Creso, was investigated. Creso is a short-strawed cultivar carrying the Gai 1 gene which influences both plant height and insensitivity to applied GA3. Cell division, as measured by mitotic index, was similar in darkness, continuous red light and dichromatic irradiation (far-red plus red), while lower mitotic rates were observed under continuous far-red light: this indicates that the response of cell division is modulated by a high-irradiance reaction of phytochrome in both cultivars. The two cultivars showed different responses to blue light. In Cappelli, blue light and dichromatic irradiation (blue plus red) gave lower mitotic indices than the dark control, indicating the action of a specific blue light-absorbing photoreceptor, whereas in Creso the response kinetics to all light regimes which included blue light were more complex. On the basis also of the results obtained with GA3 application in Cappelli, it appears that (i) the hormonal treatment is able to change the pattern of mitotic index only in the presence of the action of a blue-light receptor and (ii) the different responses of the two cultivars could be the result of different endogenous hormonal levels. The importance of the observations in relation to the data for first-leaf longitudinal growth reported in a previous paper (Baroncelli et al. 1984, Planta 160, 298-304) is discussed. PMID- 24226407 TI - Long-chain acyl CoA synthetase, carnitine and beta-oxidation in the pea-seed mitochondrion. AB - Mitochondria from pea (Pisum sativum L.) seeds were separated into two fractions, mitoplasts (intact inner membrane) and the outer-membrane fraction. The mitoplasts only oxidised palmitate in the presence of carnitine and added outermembrane fraction. Mitoplasts were able to oxidise palmitoylCoA in the presence of carnitine and added outer-membrane fraction had no effect on this oxidation. It was concluded that a long-chain acylCoA synthetase (EC 6.2.1.3) was located on the outer membrane and that the activity of this enzyme in assays was more than sufficient to account for any observed rate of O2 uptake during palmitate oxidation by pea mitochondria. The location of carnitine long-chain acyltransferase (carnitine palmitoyl transferase EC 2.3.1.21) would appear to be the mitoplast i.e. the inner mitochondrial membrane, and confirms the previous work at Newcastle. PMID- 24226408 TI - Fractional control of photosynthesis by the QB protein, the cytochrome f/b 6 complex and other components of the photosynthesic apparatus. AB - In order to obtain information on fractional control of photosynthesis by individual catalysts, catalytic activities in photosynthetic electron transport and carbon metabolism were modified by the addition of inhibitors, and the effect on photosynthetic flux was measured using chloroplasts of Spinacia oleracea L. In thylakoids with coupled electron transport, light-limited electron flow to ferricyanide was largely controlled by the QB protein of the electron-transport chain. Fractional control by the cytochrome f/b 6 complex was insignificant under these conditions. Control by the cytochrome f/b 6 complex dominated at high energy fluence rates where the contribution to control of the QB protein was very small. Uncoupling shifted control from the cytochrome f/b 6 complex to the QB protein. Control of electron flow was more complex in assimilating chloroplasts than in thylakoids. The contributions of the cytochrome f/b 6 complex and of the QB protein to control were smaller in intact chloroplasts than in thylakoids. Thus, even though the transit time for an electron through the electron-transport chain may be below 5 ms in leaves, oxidation of plastohydroquinone was only partially responsible for limiting photosynthesis under conditions of light and CO2 saturation. The energy fluence rate influenced control coefficients. Fractional control of photosynthesis by the ATP synthetase, the cytochrome f/b 6 complex and by ribulose-1,5-bisphosphate carboxylase increased with increasing fluence rates, whereas the contributions of the QB protein and of enzymes sensitive to SH-blocking agents decreased. The results show that the burdens of control are borne by several components of the photosynthetic apparatus, and that burdens are shifted as conditions for photosynthesis change. PMID- 24226409 TI - Determination of carbon-reduction-cycle intermediates in leaves of Arbutus unedo L. suffering depressions in photosynthesis after application of abscisic acid or exposure to dry air. AB - Gas exchange and contents of photosynthetic intermediates of leaves of Arbutus unedo L. were determined with the aim of recognizing the mechanisms of inhibition that were responsible for the "midday depression" of photosynthesis following exposure to dry air, and the decline in photosynthetic capacity following application of abscisic acid (ABA). Rapidly killed (<0.1 s) leaf samples were taken when gas analysis showed reduced CO2 assimilation. Determination of the contents of 3-phosphoglyceric acid (PGA), ribulose 1,5-bisphosphate (RuBP), triose phosphates, fructose 1,6-bisphosphate and hexose phosphates in the samples showed that significant variation occurred only in the level of PGA. As a result, the ratio PGA/RuBP decreased with increasing inhibition of photosynthesis, particularly when application of ABA had been the cause. A comparison of metabolite patterns did not bring out qualitative differences that would have indicated that effects of ABA and of dry air had been caused by separate mechanisms. Depression of photosynthesis occurred in the presence of sufficient RuBP which indicated that the carboxylation reaction of the carbon-reduction cycle was inhibited after application of ABA or exposure to dry air. PMID- 24226410 TI - Spermidine and flower-bud differentiation in thin-layer explants of tobacco. AB - Three lines of evidence indicate a connection between high spermidine levels and floral initiation in thin-layer tissue cultures of Wisconsin-38 tobacco (Nicotiana tabacum L.). (1) Spermidine levels are much higher in floral buds than in vegetative buds. (2) Inhibition of spermidine synthesis by cyclohexylamine prevents the rise in spermidine titer, inhibits floral initiation and promotes the formation of vegetative buds instead. (3) Application of exogenous spermidine causes floral initiation in cultures which would otherwise form vegetative buds. PMID- 24226411 TI - Vibrationally resolved absorption, emission and resonance Raman spectra of diamondoids: a study based on time-dependent correlation functions. AB - The time-dependent approach to electronic spectroscopy, as popularized by Heller and coworkers in the 1980's, is applied here in conjunction with linear-response, time-dependent density functional theory to study vibronic absorption, emission and resonance Raman spectra of several diamondoids. Two-state models, the harmonic and the Condon approximations, are used for the calculations, making them easily applicable to larger molecules. The method is applied to nine pristine lower and higher diamondoids: adamantane, diamantane, triamantane, and three isomers each of tetramantane and pentamantane. We also consider a hybrid species "Dia = Dia" - a shorthand notation for a recently synthesized molecule comprising two diamantane units connected by a C=C double bond. We resolve and interpret trends in optical and vibrational properties of these molecules as a function of their size, shape, and symmetry, as well as effects of "blending" with sp(2)-hybridized C-atoms. Time-dependent correlation functions facilitate the computations and shed light on the vibrational dynamics following electronic transitions. PMID- 24226412 TI - Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy. AB - Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as pi-pi interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the alpha-helix and increase of the beta-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green. PMID- 24226414 TI - Predicting quality of life with a pretransplantation assessment battery: A prospective study of cardiac recipients. AB - This study provides descriptive data on the prevalence of symptoms and quality of life of cardiac transplantation recipients and tests the predictive validity of a pre-cardiac transplantation psychological assessment battery on posttransplantation quality of life. Following the formation of four cluster groups of pretransplantation MMPI profiles based on previous research, frequency analysis found that the cluster groups were not equally represented among cardiac recipients, such that the "Distressed/Confused" cluster had only one recipient member. Tests of significance among the three remaining cluster groups on the posttransplantation quality of life variables found no significant differences. Regression analyses to test the predictive validity of other pretransplantation medical and psychological variables indicated that trait anxiety was a significant predictor of increased symptom frequency and symptom problems and decreased mental health among recipients. Collectively, modest support was found for the use of pretransplantation psychological variables as predictors of posttransplantation quality of life. Interpretation of psychological test data in the context of other psychosocial variables is discussed. PMID- 24226413 TI - Managing stress and managing illness: Survival and quality of life in chronic disease. AB - Interest has been steadily building in the impact of stress on psychological and physiological functioning, in particular on immune system responses, furthering the concept of a strong connection between the mind and the body. Implications for prevention of disease onset or treatment of stress-induced illness or immunocompromised conditions have been explored through the implementation of stress management techniques. Cognitive behavioral stress management interventions, biofeedback, relaxation, guided imagery, hypnosis, individual and group psychotherapy, aerobic exercise, and guided self-efficacy treatment are briefly reviewed to identify possible treatment mechanisms that may affect immune function and promote quality of life. The application of behavioral techniques to reduce distress and sharpen coping skills has great promise in reducing the costs associated with chronic disease and in enhancing quality of life among those afflicted. PMID- 24226415 TI - Quality of life and social support of patients being evaluated for bone marrow transplantation. AB - A sample of 437 patients completed self-report measures of quality of life and social support while they were being evaluated for bone marrow transplantation (BMT) at The Johns Hopkins Oncology Center. Generally, the candidates showed reasonably high levels of quality of life (QOL) on the Satisfaction with Life Domains Scale (SLDS), their present ranking on the Cantril Self-Anchoring Ladder of Life, and their scores on the Bradburn Positive Affect Scale. The level of QOL of these candidates for transplant was significantly related to their level of social support. Both availability and adequacy of social support for these transplant candidates were found to be significantly related to QOL as measured by the SLDS. Availability of social support as measured by patient membership in religious and other organizations was significantly related to Positive Affect but not Negative Affect. The Family APGAR and Relational Support Scales measures of social support were significantly correlated with both Positive and Negative Affect. PMID- 24226416 TI - Psychologists' sensitivity to medical factors examined during standard psychological evaluations: A preliminary description. AB - Medical disorders among psychiatric patients have frequently been overlooked by all mental health disciplines. These medical conditions have, at times, been later identified as influencing some of the presenting psychological symptoms. Although the relationship between medical factors and psychological symptoms has been recognized and discussed in the literature for several decades, improvement has not been well documented regarding the frequency of recognizing medical factors with psychiatric patients. Little research was found that reviewed the effectiveness of psychologists in recognizing related medical concerns. This study examined the frequency with which a random sampling of psychologists reviewed specific medical factors with their patients during the initial psychological evaluation. The results reveal that many psychologistsare sensitive to the possible influence of medical factors, which is especially important given the increased focus of psychologists as primary care providers and the increasing collaborative practice efforts between medicine and psychology. A summary and discussion of these descriptive results are presented and recommendations are offered. PMID- 24226417 TI - Teaching medical staff psychological concepts via a hospital newsletter. AB - Despite the increased recognition of the critical role of social and psychological factors in health and illness, the teaching of psychology is rarely integrated in medical education. Staff generally have minimal formal training in psychological concepts. Patients on the inpatient rehabilitation unit frequently present with unexpected reactions in response to acute trauma and resulting changes in identity and capabilities. Rehabilitation goals therefore, must be based on psychological, as well as physical, capacities. A one-page, "user friendly" newsletter was designed to illustrate basic psychological principles via case vignettes. The topics of fear, countertransference, and resistance were selected as critical issues staff frequently encounter in their work with patients. The newsletters provided the staff with basic conceptual tools for effectively treating patients, and the work of psychologists was demystified. The newsletter format is proposed as a creative adjunct to didactic teaching. PMID- 24226418 TI - Vertical integration in medical settings: A brief introduction to its potential effects on professional psychology. AB - Vertical integration in medical settings typically involves the merging of independent physicians, physician groups, and hospitals to render an organized health care network. Such systems are considered to be vertical, as they may allow for a seamless continuation of services throughout the range of needs a patient may require. Mergers often result in the redefining of professional services offered in the acquired facility or across the network. As such, mergers have the potential of adversely impacting psychological practices. Professional psychology needs to take a proactive stance in this changing health care landscape. Research regarding empirically validated treatments and effects of psychological interventions on overall health-care costs needs to be properly disseminated to health care administrators to assure their knowledge of the utility of psychological services in the medical setting. Training psychologists to assume leadership positions in health-care institutions, gaining representation on hospital staff boards, and linking psychologists and physicians through collaborative training, to provide improved care, may allow for psychology to influence health care delivery. PMID- 24226419 TI - The role of IL-32 in cutaneous T-cell lymphoma. AB - IL-32 is a pro-inflammatory cytokine expressed by activated natural killer cells, T cells, keratinocytes, and fibroblasts. In this study, we examined the role of IL-32 in cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sezary syndrome (SS). IL-32 mRNA expression levels in lesional skin of MF patch, plaque, and tumor were increased compared with those of normal skin, which positively correlated with CCL17 and CCL18 mRNA expression levels. Serum IL-32 levels positively correlated with disease activity within each patient. Immunostaining showed that keratinocytes expressed IL-32 in the lesional skin of MF patch and plaque, whereas in MF tumor, atypical T cells in the dermis strongly expressed IL-32. We also showed that IL-32 dose-dependently accelerated the proliferation of MF and SS cell lines in vitro, which was inhibited by blocking mitogen-activated protein kinase and NF-kappaB-mediated signaling. The addition of anti-IL-32 antibodies in culture decreased the proliferation of SS cells and the viability of MF cells, suggesting that IL-32 serves as an autocrine growth factor. In conclusion, our results suggest that IL-32 has a role in the formation and maintenance of CTCL lesions, providing a possible therapeutic target for patients with this disease. PMID- 24226420 TI - Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing. AB - Lipid mediators derived from 5-lipoxygenase (5-LO) metabolism can activate both pro- and anti-inflammatory pathways, but their role in wound healing remains largely unexplored. In this study we show that 5-LO knockout (5-LO(-/-)) mice exhibited faster wound healing than wild-type (WT) animals, and exhibited upregulation of heme oxygenase-1 (HO-1). Furthermore, HO-1 inhibition in 5-LO(-/ ) mice abolished the beneficial effect observed. Despite the fact that 5-LO(-/-) mice exhibited faster healing, in in vitro assays both migration and proliferation of human dermal fibroblasts (HDFs) were inhibited by the 5-LO pharmacologic inhibitor AA861. No changes were observed in the expression of fibronectin, transforming growth factor (I and III), and alpha-smooth muscle actin (alpha-SMA). Interestingly, AA861 treatment significantly decreased ROS formation by stimulated fibroblasts. Similar to 5-LO(-/-) mice, induction of HO 1, but not superoxide dismutase-2 (SOD-2), was also observed in response to 5-LO (AA861) or 5-LO activating protein (MK886) inhibitors. HO-1 induction was independent of nuclear factor (erythroid derived-2) like2 (Nrf-2), cyclooxygenase 2 (COX-2) products, or lipoxin action. Taken together, our results show that 5-LO disruption improves wound healing and alters fibroblast function by an antioxidant mechanism based on HO-1 induction. Overexpression of HO-1 in wounds may facilitate early wound resolution. PMID- 24226421 TI - Tumor necrosis factor-alpha and apoptosis induction in melanoma cells through histone modification by 3-deazaneplanocin A. PMID- 24226422 TI - CD271 on melanoma cell is an IFN-gamma-inducible immunosuppressive factor that mediates downregulation of melanoma antigens. AB - IFN-gamma released from cytotoxic T lymphocytes (CTLs) during the effector phase is essential for rejecting bulky melanoma tumors. In contrast, IFN-gamma is known to induce certain immunosuppressive factors in tumor cells such as programmed cell death 1 ligand 1 (PD-L1). In this study, we have identified candidates for IFN-gamma-inducible CTL-suppressive factors in melanoma cells using complementary DNA microarray analysis, and CD271/p75/neurotrophin receptor (NTR) was one of the candidate genes. Recently, CD271 was identified as a marker of the cancer stem cell-like population in human melanoma tissues. In this study, we showed that overexpression of CD271 on melanoma cells suppressed the in vitro activation of melanoma-specific CTLs. This suppression was mediated by CD271 ligation with activated CTL-derived nerve growth factor and the subsequent downregulation of melanoma antigens. Moreover, we found that the expression levels of PD-L1 on melanoma cells correlated with those of CD271, and they additively suppressed the activation of melanoma-specific CTLs. To the best of our knowledge, the role of overexpression of CD271 in an anti-melanoma T-cell response has been unreported. PMID- 24226423 TI - Increased beta-adrenergic inotropy in ventricular myocardium from Trpm4-/- mice. AB - RATIONALE: The Trpm4 gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca2+ -activated, but Ca2+ impermeable, nonselective cation channels and are expressed both in atrial and in ventricular cardiomyocytes. The physiological function of TRPM4 in the heart remains, however, incompletely understood. OBJECTIVE: To establish the role of TRPM4 in cardiac muscle function. METHODS AND RESULTS: We used TRPM4 knockout mice and performed patch-clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure-volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca2+ -induced Ca2+ release. In Trpm4(-/ ) mice, cardiac muscle displays an increased beta-adrenergic inotropic response both in vitro and in vivo. Measurements of action potential duration show a significantly decreased time for 50% and 90% repolarization in Trpm4(-/-) ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L-type Ca2+ current during the action potential, which explains the altered contractility of the heart muscle. CONCLUSIONS: Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of beta-adrenergic stimulation on the ventricular heart muscle. PMID- 24226424 TI - Middle cerebral artery bifurcation aneurysms: an anatomic classification scheme for planning optimal surgical strategies. AB - BACKGROUND: Changing landscapes in neurosurgical training and increasing use of endovascular therapy have led to decreasing exposure in open cerebrovascular neurosurgery. To ensure the effective transition of medical students into competent practitioners, new training paradigms must be developed. OBJECTIVE: Using principles of pattern recognition, we created a classification scheme for middle cerebral artery (MCA) bifurcation aneurysms that allows their categorization into a small number of shape pattern groups. METHODS: Angiographic data from patients with MCA aneurysms between 1995 and 2012 were used to construct 3-dimensional models. Models were then analyzed and compared objectively by assessing the relationship between the aneurysm sac, parent vessel, and branch vessels. Aneurysms were then grouped on the basis of the similarity of their shape patterns in such a way that the in-class similarities were maximized while the total number of categories was minimized. For each category, a proposed clip strategy was developed. RESULTS: From the analysis of 61 MCA bifurcation aneurysms, 4 shape pattern categories were created that allowed the classification of 56 aneurysms (91.8%). The number of aneurysms allotted to each shape cluster was 10 (16.4%) in category 1, 24 (39.3%) in category 2, 7 (11.5%) in category 3, and 15 (24.6%) in category 4. CONCLUSION: This study demonstrates that through the use of anatomic visual cues, MCA bifurcation aneurysms can be grouped into a small number of shape patterns with an associated clip solution. Implementing these principles within current neurosurgery training paradigms can provide a tool that allows more efficient transition from novice to cerebrovascular expert. PMID- 24226425 TI - High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory Cushing disease from capecitabine and temozolomide (CAPTEM): a case series. AB - BACKGROUND AND IMPORTANCE: Rarely, corticotrophic pituitary tumors take on an aggressive form characterized by rapid growth, invasion into local structures, compression of cranial nerves, and possible spread to distant sites. When conventional surgery, radiation therapy, and hormones fail to control progression and symptoms, alternative therapies are needed. A novel chemotherapeutic regimen of capecitabine and temozolomide (CAPTEM), originally designed in our laboratory, demonstrated dramatic antineoplastic effects against corticotrophic pituitary tumors. CLINICAL PRESENTATION: We present a case series of 4 patients with aggressive, adrenocorticotrophic hormone--producing pituitary tumors who had previously depleted all surgical, radiation, and hormonal therapies and were then treated with CAPTEM. Dramatic clinical improvements in neurological deficits and Cushing symptoms were evident in all patients after treatment was initiated. Confirmed by radiographic imaging, 2 of 4 patients demonstrated complete regression of disease, 1 patient had a 75% regression, and the fourth patient has ongoing stable disease for > 4.5 years at the time of this writing. Immunohistochemical analysis of patients' tumor samples showed low O-methyguanyl methyltransferase expression and adequate levels of mismatch repair enzymes (MLH 1, MSH-2, MSH-6, and PMS-2), which are important for the in vivo efficacy of CAPTEM. CONCLUSION: This is the first report of prolonged antitumor response to and radiographic complete remissions as a result of CAPTEM in patients with aggressive pituitary tumors who had exhausted all other therapies. PMID- 24226426 TI - Allogeneic bone marrow mesenchymal stem cell transplantation for periodontal regeneration. AB - In this study, we investigated the possibility of using local administration of allogeneic bone marrow mesenchymal stem cells (BMMSCs) to induce tissue regeneration in periodontal defects in a rat model of periodontitis. BMMSCs isolated from rats were mixed with 0.9% NaCl solution and injected into periodontal defects. Control groups were 0.9% NaCl solution or left untreated. The clinical assessments, x-rays, and histological examinations were used to evaluate the effect. At 12 wks post-transplantation, quantitative analysis revealed average probing bone loss values of 1.2 +/- 0.19, 1.6 +/- 0.2, and 1.7 +/- 0.14; the bone regeneration rate was 53%, 45%, and 44% in the BMMSC+NaCl group, NaCl group, and untreated group, respectively. The clinical assessments, x rays, and histological examinations revealed significant periodontal tissue regeneration in the BMMSC injection group, compared with the control groups. The ELISA results showed that TNFalpha, IFNgamma, and IL1beta were 2,674.88 +/- 102.77 pg/mL vs. 3,422.1 +/- 51.98 pg/mL, 609.85 +/- 25.5 pg/mL vs. 803.79 +/- 33.85 pg/mL, and 1,038.46 +/- 76.29 pg/mL vs. 1,175.26 +/- 105.55 pg/mL in the BMMSC+NaCl group and NaCl group, respectively, indicating that BMMSC injection inhibited the inflammatory factors TNFalpha, IFNgamma, and IL1beta. Our results indicate that local administration of BMMSCs can repair defects due to periodontitis, exerting anti-inflammatory and immunomodulatory functions. PMID- 24226427 TI - How important is it to keep taking the aspirin? PMID- 24226429 TI - Meristem transformation of sunflower via Agrobacterium. AB - For transformation of sunflower (Helianthus annuus L. cv. Zebulon), shoot apical meristems were dissected from seeds and cocultivated with a disarmed Agrobacterium tumefaciens strain harboring a binary vector carrying genes encoding GUS- and NPTII-activity. The influence of the media conditions, the time of cocultivation and the stage of the developing seed on shoot development and meristem transformation was analysed. Transformants were selected by their ability to grow on kanamycin. Transformation was confirmed by assays for GUS and NPTII. GUS-positive shoots were rooted on rockwool and transferred to soil. Transformation of shoot meristem cells occurred at low frequencies. Chimaeric expression of the two genes was observed in transformed plants. Integration of the foreign DNA in the sunflower genome was confirmed with the polymerase chain reaction. PMID- 24226428 TI - Clinical and immunologic factors associated with bullous pemphigoid relapse during the first year of treatment: a multicenter, prospective study. AB - IMPORTANCE: Although predisposing factors for bullous pemphigoid (BP) have been recently established, no clinical or immunologic factors have yet been identified to predict disease outcome. OBJECTIVE: To identify risk factors for BP relapse during the first year of treatment. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study of 120 consecutive patients with newly diagnosed BP in 8 French dermatology departments. Baseline and 6 follow-up visits were planned to record disease activity and collect blood samples for measurement of serum anti-BP180 and anti-BP230 levels by means of enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOMES AND MEASURES: The end point was clinical relapse within the first year of therapy. Associations of clinical and immunologic (including serum levels of anti-BP180 and anti-BP230 autoantibodies) parameters with clinical relapse were assessed using univariate and multivariate analyses. RESULTS: During the 1-year follow-up, 35 patients (29.2%) experienced relapse, whereas anti-BP180 and anti-BP230 ELISA results were similar at baseline between patients who did and did not experience relapse. Factors at baseline independently associated with relapse were extensive disease at inclusion (hazard ratio [HR], 2.37 [95% CI, 1.2-4.8]) and an associated dementia (HR, 2.09 [95% CI, 1.0-4.2]). Use of superpotent topical corticosteroids alone (by 100 patients [83.3%]) induced a dramatic, early decrease in serum levels of anti-BP180 and anti-BP230 autoantibodies. Mean early decreases in autoantibody levels between baseline and day 60 were lower in patients with relapse compared with patients with ongoing remission (-10.0% and -45.2%, respectively, for anti-BP180 levels [P < .001] and -11.8% and -35.4%, respectively, for anti-BP230 levels [P = .046]). A higher serum level of anti-BP180 at day 150, with a cutoff of 23 U/mL, provided 84.2% sensitivity, 44.8% specificity, 33.3% positive predictive value, and 89.7% negative predictive value for the occurrence of relapses between days 150 and 360. CONCLUSIONS AND RELEVANCE: The pronounced decrease in the level of anti BP180 autoantibodies and, to a lesser extent, those directed against BP230 confirmed the use of superpotent topical corticosteroids alone as a reference BP treatment. Furthermore, our study suggests that neurological diseases play a major role in BP, not only as a predisposing but also as a prognostic factor. PMID- 24226430 TI - Isolation, culture and plantlet regeneration from cotyledon and mesophyll protoplasts of two pickling cucumber (Cucumis sativus L.) genotypes. AB - Optimal protoplast yields from cotyledons (2.0*10(6) protoplasts/ 0.5 g tissue) and from true leaves (5.0*10(6) protoplasts/g tissue) of two Cucumis sativus genotypes were obtained following a 16 h digestion with, respectively, 1.25% pectinase+0.5% Cellulysin and 0.5 % pectinase+ 1.0% Cellulysin. Enzyme solutions were prepared in modified MS medium containing half-strength major salts, full complement of minor salts and vitamins, 2% sucrose and 0.25 M mannitol. A plating density of 3.5-4.0* 10(4) protoplasts/ml or higher was required for sustained division, with first division occurring in 6-7 days, second-third division in 8-9 days, and minicalli formation by day 13. Embedding in 0.4% agarose provided the highest plating efficiency (proportion that formed minicalli) of mesophyll protoplasts, which was 28.3% for genotype 3672 and 15% for genotype 3676. By comparison, liquid culture and droplet culture gave lower plating efficiencies (10-19%). Cotyledon and mesophyll protoplasts of one genotype formed minicalli on MS medium containing 2,4-D/BA at 1.0/2.5 MUM and 5.0/5.0 MUM, respectively, within 21 days, while mesophyll protoplasts of the second genotype formed minicalli on MS medium containing NAA/BA at 5.0/5.0 MUM within 12 days. Shoot buds or somatic embryos were obtained upon subculture of calli to MS medium containing lower concentrations (0.05-0.01 MUM) of 2,4-D/BA or NAA/BA and a few plantlets, ca.18, were recovered on hormone-free medium. PMID- 24226431 TI - Production of theanine and other gamma-glutamyl derivatives by Camellia sinensis cultured cells. AB - The maximum theanine production by Camellia sinensis cultured cells was achieved by culturing in the modified MS medium containing 2 mg/l indole-3-butyric acid, 0.1 mg/l kinetin, 0 mM NH4NO3 and 39.6 mM KNO3 with 40 mM ethylamine hydrochloride or 20 mM ethylamine hydrochloride and 10 mM L-glutamic acid. Other primary amines, such as methylamine, n-butylamine, 2-hydroxyethylamine, 2cyanoethylamine, aniline, benzylamine and phenylethylamine, were also biotransformed to N(5)-alkyl-L-glutamine derivatives by C. sinensis cultured cells. PMID- 24226432 TI - Improved plant regeneration from shed microspore culture in barley (Hordeum vulgare L.) cv. igri. AB - This report describes rapid regeneration of green plants from microspores of the barley cultivar Igri. Use of 0.3 M mannitol during maceration and isolation was essential for response from mechanically isolated microspores of barley cv. Igri grown under our conditions. A shed microspore culture system proved to be simple and gave a fast response; plants were obtained as early as 25 days after the material was taken from the donor plant. A 28-day cold-pretreatment of spikes can also be replaced with a 3-4 day pretreatment of anthers in mannitol. Shed microspores from 100 anthers produced an average of 292 plants with 91% of them green. Approximately 80% of the regenerated plants were spontaneously doubled haploids. PMID- 24226433 TI - Induction of shikonin biosynthesis by endogenous polysaccharides in Lithospermum erythrorhizon cell suspension cultures. AB - Endogenous polysaccharides capable of inducing shikonin biosynthesis in a growth medium were isolated from shikonin-producing Lithospermum cells cultured in a production medium. Chemical analysis showed that these active polysaccharides consist of galacturonic acid, galactose, arabinose and glucose. Their activity, however, was lost by a treatment with pectinlyase. Addition of a small amount of pectinase to cell cultures in the growth medium induced shikonin formation. This is the first report that endogenous polysaccharides participate in inducing normal secondary metabolism of higher plants. PMID- 24226434 TI - Somatic embryogenesis and shoot organogenesis from interspecific hybrid embryos of Vigna glabrescens and V. radiata. AB - Somatic embryogenesis occurred on cotyledons of morphologically abnormal embryos derived from Vigna glabrescens x V. radiata crosses and cultured on Murashige and Skoog (MS) medium without growth regulators. The frequency of 15-17 day old embryos that gave rise to somatic embryos increased from 8% to 29% by application a mixture of 100 mg/l gibberelllc acid, 25 mg/l alpha-naphthaleneacetic acid (NAA) and 5 mg/l kinetin daily to the pedicels of the developing pods. However, only callus formed on immature hybrid embryos of the reciprocal cross. These callus tissues occasionally gave rise to shoots via organogenesis when transferred to MS medium with 2 mg/l N(6)-benzyladenine and 0.05 mg/l NAA. Treatment of pods with growth regulators did not influence the frequency of organogenic callus. Selfed embryos of the parents did not form somatic embryos in culture, nor did callus derived from the selfed embryos produce shoots. Thus, the ability to redifferentiate appears to be associated with interspecific hybridity. PMID- 24226435 TI - Growth, ammonia accumulation and glutamine synthetase activity in alfalfa (Medicago sativa L.) shoots and cell cultures treated with phosphinothricin. AB - Phosphinothricin is a non-selective herbicide which inhibits glutamine synthetase (EC 6.3.1.2) activity causing an overaccumulation of ammonia in higher plants. Alfalfa (Medicago sativa L) shoot tissue and petiole-derived callus exposed to phosphinothricin show 50 and 70% reductions, respectively, in glutamine synthetase activity with a concomitant rise of 10 and 20 fold, respectively, in endogenous ammonia. The diffusibility of ammonia may limit the use of a detoxifying gene, phosphinothricin acetyltransferase, as a selectable marker for alfalfa transformation. However, the addition of up to 40 times the standard levels of ammonium nitrate to the culture media used in this study had no effect on callus growth, although glutamine synthetase activity was inhibited by 50% and endogenous ammonia increased 27 fold. Therefore, ammonia accumulation may not be the primary cause of cell death in alfalfa after exposure to phosphinothricin. It follows that diffusion of ammonia from cell to cell would not restrict the selection for phosphinothricin acetyltransferase transformed cells, thereby indicating that this enzyme could be used as a selectable marker in transformation experiments. PMID- 24226436 TI - Regeneration of Lycium barbarum L. plants from leaf tissue, callus culture and callus protoplasts. AB - The possibility of plant regeneration from leaf tissue, callus and callus protoplasts of Lycium barbarum L. has been studied. Leaf segments were cultured on B5 medium (Gamborg et al. 1968) containing 1.5 mg/1 6-benzylaminopurine and 0.5 mg/1 alpha-naphthaleneacetic acid. Regeneration of shoots was initiated after 30 days of cultivation. Callus was obtained from leaf and internode tissues on MS medium (Murashige and Skoog 1962) containing 0.4 mg/1 of 2,4dichlorophenoxyacetic acid. Subsequently, callus was successfully subcultured on the same medium with 1 mg/l of 2,4-dichlorophenoxyacetic acid and 0.2 mg/l alpha-naphthaleneacetic acid. Organogenesis in callus culture was obtained in the course of 40 days after transferring to TM-4 (Shahin 1984). Protoplasts were isolated from callus tissue grown in vitro using an enzymatic method. Cell colonies, minicallus formation and organogenesis were obtained. Shoots were rooted on Murashige and Skoog medium containing 0..1 mg/l alpha-naphthaleneacetic acid. Regenerated plants were transferred to soil and were grown to maturity. Regenerated plants carried normal morphological traits. PMID- 24226438 TI - High frequency embryoid and plantlet formation from tissue cultures of the Finger millet-Eleusine coracana (L.) Gaertn. AB - Compact nodulated embryogenic callus differentiated from cultured seeds of Eleusine coracana (Finger Millet) on Murashige and Skoog (1962) basal medium with 2,4-dichlorophenoxyacetic acid (1.0, 3.0 mg (l)). This embryogenic callus was maintained on a medium with a lower level of 2,4 - dichlorophenoxyacetic acid. At every subculture the embryogenic callus had some preexisting embryoids in it. With this method of subculture the callus has retained its morphogenic potential for four years. Following transfer to media with different levels of auxins and cytokinins, the callus showed varied patterns of growth and morphogenesis. Embryoids could be germinated in profusion to form plantlets which could be transferred to the field. Shoot buds also differentiated from the whole surface of the embryoid or from the flattened meristemoids. PMID- 24226437 TI - Recovery of morphologically normal transgenic tobacco from hairy roots co transformed with Agrobacterium rhizogenes and a binary vector plasmid. AB - Co-transformation of tobacco (Nicotiana tabacum) leaf explants with Agrobacterium rhizogenes harbouring pRi1855 and the binary vector pBin19 was achieved at a frequency of 67%. The kanamycin resistant hairy roots were cultured via a callusing phase to regenerate plants which were partially fertile when outcrossed with wild-type pollen. Phenotypic and molecular analysis of the F1 progeny demonstrated the efficient segregation of the hairy root marker from the kanamycin resistance marker, enabling morphologically normal plants to be recovered which retained the binary vector marker gene. This co-transformation strategy provides a means of introducing non-selectable genes into plants in cases where antibiotic resistance markers are undesirable. PMID- 24226439 TI - Increased podophyllotoxin production in Podophyllum hexandrum cell suspension cultures after feeding coniferyl alcohol as a beta-cyclodextrin complex. AB - Cell suspension cultures, derived from roots of Podophyllum hexandrum Royle (Berberidaceae), accumulate podophyllotoxin. In this study the use of beta cyclodextrin in feeding the poorly water-soluble precursor coniferyl alcohol to these cultures is described. By complexation with beta-cyclodextrin, a solution of 3 mM coniferyl alcohol could be fed, resulting in enhanced podophyllotoxin accumulation. The same concentration of non-complexed suspended coniferyl alcohol had only little effect on the podophyllotoxin accumulation. beta-Cyclodextrin itself was proven to be non-toxic for the cells. It did not influence the podophyllotoxin content and it was not metabolized or used as a carbon source by the cells. For comparison, coniferin, the water-soluble beta-D-glucoside of coniferyl alcohol, was also fed in the same concentration. The effect of coniferin on the podophyllotoxin accumulation was stronger than that of coniferyl alcohol complexed with beta-cyclodextrin, but coniferin is not commercially available. PMID- 24226440 TI - Alkaloids of hairy root cultures of a Datura candida hybrid. AB - From the in vitro hairy root cultures of a Datura candida hybrid, 19 tropane alkaloids have been identified using capillary gas-liquid chromatography and mass spectrometry. As in the parent plants, scopolamine is the major alkaloid. Two hitherto undescribed alkaloids have been detected and their structure tentatively characterised on the basis of their mass spectral fragmentations. PMID- 24226441 TI - Temporary inhibition of cell wall synthesis improves the transient expression of the GUS gene in Brassica napus mesophyll protoplasts. AB - Transformation of Brassica napus mesophyll protoplasts was performed with the beta-glucuronidase gene fusion system. After electroporation, transient expression in protoplasts transformed directly after isolation was about 1 to 2 per million. By the use of 2,6-dichloro-benzonitrile, a non-toxic inhibitor of cell wall synthesis, and in the presence of 5% polyethyleneglycol, transformation of the cell material was performed three days after isolation. At that time, about 25-30% of the protoplasts had reached the first S-phase of the mitotic cycle. A 1000 fold increase of protoplasts expressing the beta-glucoronisidase gene transiently was obtained, in the partly synchronized protoplasts, compared to those transformed directly after isolation. PMID- 24226442 TI - Plant regeneration from protoplasts of Felicia and Brachycome. AB - Protoplasts were isolated from leaves of axenic shoot cultures of Felicia bergeriana (Kingfisher Daisy) and Brachycome iberidifolia (Swan River Daisy) and from callus cultures of Felicia. Plants were regenerated from all three sources and since both species are of ornamental value (blue flowered) the establishment of plant regeneration provides a basis for their incorporation in somatic hybridisation programmes involving important ornamentals such as Chrysanthemum. PMID- 24226443 TI - Tetraploids, triploids, and 2n pollen from diploid interspecific crosses with cassava. AB - Interspecific crosses of five cultivated cassava varieties (2n=36) were made with two related Manihot species, M. epruinosa (2n=36) and M. glaziovii (2n=36). From these diploid interspecific crosses, four spontaneous tetraploids (2n=4x=72) and two triploids (2n=3x=54) were isolated for the first time in cassava. Occurrence of relatively high frequencies (0.1%-35.6%) of 2n pollen and of apomixis seems to be associated with sexual polyploidization. The tetraploids and triploids were very vigorous and one of the tetraploids performed as well as the best variety in uniform yield trials conducted in Nigeria. These spontaneous polypoloids provide greater genetic variation and offer an opportunity to breed radically new cassava varieties. Approaches for isolating and utilizing the polyploid cassava clones for varietal and population improvement are discussed. PMID- 24226444 TI - Comparison of chloroplast and mitochondrial DNA from five morphologically distinct Beta vulgaris cultivars: sugar beet, fodder beet, beet root, foliage beet, and Swiss chard. AB - Two cytoplasms, N and S, are used in the breeding of sugar beet, Beta vulgaris var. altissima. These cytoplasms can be distinguished by their mitochondrial DNA. In an attempt to detect new cytoplasms, we compared the restriction profiles of chloroplast and mitochondrial DNA from five different cultivars of Beta vulgaris. All restriction patterns of chloroplast DNA were identical. With the exception of sugar beet with S-cytoplasm, all cultivars studied showed the same restriction profile of mitochondrial DNA, indicating that these cultivars all contain the N cytoplasm. These results are discussed with regard to the large morphological differences of the cultivars and the cytoplasmic variability found in natural populations of the wild beet, Beta maritima. PMID- 24226445 TI - Quantitative analysis of resistance in cotton to three new isolates of the bacterial blight pathogen. AB - Genetic variability for virulence of the bacterial blight pathogen [Xanthomonas campestris pv malvacearum (Smith) Dye] on cotton (Gossypium hirsutum L.) has been shown by the identification of 19 races of the pathogen based on disease reactions of a set of ten host differentials. This study was conducted to determine the inheritance of host resistance to three recently identified isolates of X. campestris pv malvacearum, which are virulent on the entire set of differentials. True leaves of Tamcot CAMD-E, LEBOCAS-3-80, Stoneville 825, and their f1, F2, and backcross progenies were wound-inoculated in the field with separate bacterial suspensions of the virulent HV3, HV7, and Sudan isolates of the pathogen. LEBOCAS-3-80 was replaced with S295, a new immune cultivar, for a greenhouse study in which both cotyledons and true leaves were inoculated. Disease reactions were rated on a scale of 1-10, and genetic models were proposed utilizing generation means analysis. Dominance, when significant, was in the direction of resistance in all but one cross-isolate combination. Digenic interaction components indicated a duplicate type. Narrow-sense heritability for resistance ranged from 0.59 to 0.68; therefore, primarily additive-genetic variability among the selected cutlivars was detected, indicating that breeding for improved resistance to these isolates is a practical goal. PMID- 24226446 TI - Somatic Mutator activity expression is dependent on the strength of Cy trans active signals in maize. AB - Two receptor element alleles (vp-rcy and bz-rcy) that respond to the trans-active element (Cy) controlling Mutator activity were used to analyze the strength of trans-active signals from Cy elements derived from a Mutator active line. Evidence is presented that the Mutator population tested consists mainly of a class of weak Cy elements designated as Cy:Mu. When Cy:Mu element are present in only a few copies, the strength of the combined transposition signal is weak. It is only when these active elements have a high copy number that the overall transposition signal is sufficiently strong enough to elicit a high frequency of transposition events. This study seeks to investigate the nature of the trans active signal from Cy:Mu elements. The implication of these results for molecular studies is discussed. PMID- 24226447 TI - Numbers of sporophytic self-incompatibility alleles in populations of wild radish. AB - To estimate the numbers of sporophytic S-alleles in two adjacent populations of wild radish, we performed 701 reciprocal crosses among 50 individuals. Each cross was replicated five times in each direction. Sixteen plants were fully intercompatible, indicating the presence of at least 32 S-alleles in the two populations. A minimum of 22 S-alleles occur in a single population. The frequency of incompatibility was significantly higher for within-population crosses (14.5%) than for between-population crosses (7.8%). This suggests that the two populations differ in the composition and frequency of alleles at the S locus. PMID- 24226448 TI - Cytogenetic studies in the genus Zea : 2. Colchicine-induced multivalents. AB - Premeiotic colchicine treatment brings about the production of one to five quadrivalents in Zea mays ssp. mays (maize, 2n=20) and an increase in the number of quadrivalents from five to ten in Zea perennis (2n=40). The results confirm the allotetraploid nature of maize and suggest that the species possesses two homoeologous genomes (A2A2 B2B2) that fail to pair, probably due to the presence of Ph-like genes. Moreover, the autoallooctoploid nature of Zea perennis, with a genome formula A'1A'1 A"1A"1 C1C1 C2C2, is supported by the present results. PMID- 24226449 TI - Genetic analysis of soybean hard seededness with molecular markers. AB - Hard seededness in soybean [Glycine max (L.) Merr.] is a quantitative trait that affects the germination rate, viability, and quality of stored seeds. We have used 72 restriction fragment length polymorphisms (RFLPs) to identify genomic regions containing quantitative trait loci (QTL) affecting hard seededness in a segregating population from a G. max by a Glycine soja (Sieb. & Zucc.) cross. Five independent RFLP markers were found to be associated with variation in the hard-seeded trait. These markers and the epistatic interactions between them explain 71% of the variation for hard seededness. A genomic region associated with the i locus accounted for 32% of the variation in this segregating population. This study illustrates one approach to physiological genetic studies in plants. PMID- 24226450 TI - Genome size variation in Zea mays ssp. mays adapted to different altitudes. AB - Previous studies have indicated a positive correlation between genome size and altitude among plant species. It has been hypothesized that increasing genome size occurs due to increasing C-banded heterochromatin. In corn, increasing altitude has been correlated with decreasing knob (C-banded) heterochromatin, suggesting that DNA content may decrease with increasing altitude. In this study, nuclear DNA content of 12 southwestern United States Indian maize populations, collected at various altitudes, was determined. The significant positive correlation observed between genome size and altitude suggests that corn follows the trend of increasing DNA content with increasing altitude observed in other plant species. Whether this correlation is due to increasing knob heterochromatin or additional intra- or supernumerary chromosomal DNA sequences has yet to be determined. PMID- 24226451 TI - Genetic elements inducing gene changes at the pallida locus of Antirrhinum majus. AB - The pal-rec-low-o is a special repressed state of the pallida-recurrens allele, which normally mutates from the recessive to the dominant condition, giving pigmented Pal spots on corolla lobes. The pal-rec-low-o in the homozygous condition is stably colorless (except for rare mutant spots), but when crossed with the recessive tester strain, pal-tub pal-tub (also stably colorless), the mutation frequency of the particular repressed state of pal-rec (i.e., pal-rec low-o) increases spectacularly, giving several shifts of varying sizes. The evidence suggests that the activity of the repressed state of the: pal-rec-low-o allele is dependent on the presence of an independently located Pr element, contributed by the pal-tub tester strain. In the absence of such a regulatory element, the repressed allele exhibits stable expression due to the effect of a "repressor" Rp element residing at or near the locus. It has also been shown that the pal-tub regulatory element, Pr, while coming through a phase of heterozygosity, could be changed either by picking up an element from the stabilized colorless "original" strain which, being dominant, suppresses the gene action completely; or a change may take place in pal-tub's own regulatory machinery, which otherwise has characteristics of gene regulation. However, the pal-tub regulatory element, when inactive, can be made trans-active by introducing a fresh regulator into the genome, which may segregate at meiosis. PMID- 24226452 TI - Genetic analysis of ecologically relevant morphological variability in Plantago lanceolata L. : 5. Diallel analysis of two natural populations. AB - Morphological variability was studied in two populations of Plantago lanceolata using diallel analysis. In each population, reciprocal crosses between all possible pairs of ten plants were made. In the greenhouse, six members of each family were grown and many characters were measured. Using the model of Cockerham and Weir, the contributions of the different genetic variance components were calculated. From earlier papers it was postulated in advance to what extent and by which effect the characters in both populations were genetically determined. The populations had been differentiated for life history and morphological characters, and varied also in the relative contribution of genetic components to variability. In the Merrevliet (Me) population, where strong biotic selection was assumed, low levels of additive-genetic variability were present and the relative dominance appeared to be high. The contrasting population, Westduinen (Wd), which is abiotically controlled and shows strong environmental variability, possessed higher levels of additive-genetic variability and lower levels of relative dominance. It is possible that differential natural selection has diminished additive-genetic variability to different extents in both populations: plasticity and environmental heterogeneity prevented the loss of additive-genetic variability in Wd, whereas in the stable population, Me, natural selection had the opportunity of not only changing the means of the characters but also of diminishing additive-genetic variability to a great extent. PMID- 24226453 TI - Mapping of ripening-related or -specific cDNA clones of tomato (Lycopersicon esculentum). AB - Nineteen ripening-related or -specific clones from Lycopersicon esculentum were mapped via RFLP analysis using an F2 population from the cross L. esculentum x L. pennellii and cDNA or genomic clones of known map location. The map produced using cDNA and genomic clones of known map location corresponded well with previously published maps of tomato. The number of loci detected for each ripening-related or-specific clone varied from one to seven. These loci were located on all 12 chromosomes of the tomato genome. There was no significant clustering of ripening-related or-specific genes. Regions of very low recombination were observed. The clone for polygalacturonase (TOM6) mapped to a single region on chromosome 10, the same chromosome as the nor and alc ripening mutants. To fine map this chromosome, two backcross populations were produced from the cross of L. esculentum x L. pimpenillifolium, in which the esculentum parents used were homozygous for either the alc or the nor. The coding region for polygalacturonase is functionally unlinked to either of these two ripening mutants. PMID- 24226455 TI - Prediction of the performance of inbred lines derived from a population cross in autumn-sown onions (Allium cepa L.). AB - A design and model are presented to allow the prediction, in early generations, of the mean and distribution of recombinant inbred lines derived from a cross between two parental populations or partially inbred lines. The procedure has been tested in autumn-sown onions (in the UK) using a wide cross between the openpollinated Japanese cultivar, Senshyu, and a partially inbred line derived from the European cultivar, Rawska. The early generations used for prediction included the first self-pollinated generation of the two parental populations and the F3 generation produced from the hybrid population. The predictions were tested by reference to the field performance of a random array of inbred lines, which were produced by single-seed descent (SSD) and had been selfed for three generations. The early generations, used for prediction, and a sample of SSD lines were raised alongside each other in each of two seasons. Within each season, good agreement was found between the predicted and observed performance of the recombinant inbred lines for three characters - yield, quality and maturity. This is used as evidence of the validity of the genetical model and the assumptions made. The effects of genotype x environment interactions prevented predictions made in one season being reliably applied to those made in the other and, therefore, reduce the attraction of this type of prediction study to the plant breeder. PMID- 24226454 TI - Brassica taxonomy based on nuclear restriction fragment length polymorphisms (RFLPs) : 3. Genome relationships in Brassica and related genera and the origin of B. oleracea and B. rapa (syn. campestns). AB - RFLPs were used to study genome evolution and phylogeny in Brassica and related genera. Thirtyeight accessions, including 10 accessions of B. rapa (syn. campestris), 9 cultivated types of B. oleracea, 13 nine-chromosome wild brassicas related to B. oleracea, and 6 other species in Brassica and allied genera, were examined with more then 30 random genomic DNA probes, which identified RFLPs mapping to nine different linkage groups of the B. rapa genome. Based on the RFLP data, phylogenetic trees were constructed using the PAUP microcomputer program. Within B. rapa, accessions of pak choi, narinosa, and Chinese cabbage from East Asia constituted a group distinct from turnip and wild European populations, consistent with the hypothesis that B. rapa had two centers of domestication. A wild B. rapa accession from India was positioned in the tree between European types and East Asian types, suggesting an evolutionary pathway from Europe to India, then to South China. Cultivated B. oleracea morphotypes showed monophyletic origin with wild B. oleracea or B. alboglabra as possible ancestors. Various kales constitute a highly diverse group, and represent the primitive morphotypes of cultivated B. oleracea from which cabbage, broccoli, cauliflower, etc. probably have evolved. Cauliflower was found to be closely related to broccoli, whereas cabbage was closely related to leafy kales. A great diversity existed among the 13 collections of nine-chromosome wild brassicas related to B. oleracea, representing various taxonomic states from subspecies to species. Results from these studies suggested that two basic evolutionary pathways exist for the diploid species examined. One pathway gave rise to B. fruticulosa, B. nigra, and Sinapis arvensis, with B. adpressa or a close relative as the initial ancestor. Another pathway gave rise to B. oleracea and B. rapa, with Diplotaxis erucoides or a close relative as the initial ancestor. Raphanus sativus and Eruca sativus represented intermediate types between the two lineages, and might have been derived from introgression or hybridization between species belonging to different lineages. Molecular evidence for an ascending order of chromosome numbers in the evolution of Brassica and allied genera was obtained on the basis of RFLP data and phylogenetic analysis. PMID- 24226456 TI - Asymmetric hybridization in Nicotiana by "gamma fusion" and progeny analysis of self-fertile hybrids. AB - Mesophyll protoplasts of the nitrate-reductase (NR)-deficient Nicotiana plumbaginifolia mutant, "Nia26", were fused with gamma-irradiated mesophyll protoplasts of Nicotiana sylvestris, V-42. Hybrid selection was based on complementation of NR deficiency by transfer of the donor NR gene to N. plumbaginifolia. Regenerated hybrids had different numbers of donor chromosomes in a tetraploid background of N. plumbaginifolia. The transfer and expression of different isozymes from the donor were also observed. Six self-fertile regenerants were obtained from 21 independently isolated cell colonies. Progeny analyses revealed: (1) the linkage of NR and shikimate dehydrogenase (ShDh); (2) a stabilization of the transmission rate of NR; and (3) the obtainment of mono- and disomic addition lines in the first and second progeny of the original regenerants. Southern hybridization analyses demonstrated unequivocally the presence of the NR gene from the donor partner in progeny plants. PMID- 24226457 TI - Effects of the d 2 dwarfing gene in pearl millet. AB - Dwarf varieties have had virtually no impact on the production of pearl millet, in contrast to the case of wheat, rice, and sorghum. This research compared tall and dwarf near-isogenic F1 hybrids to attempt to determine if there were deleterious effects of the d 2 dwarfing gene that might account for the lack of release/cultivation of dwarf pearl millet cultivars. Dwarf isohybrids on average yielded less than the tails, because of a smaller average seed size combined with a similar grain number per unit area. There was, however, a larger contribution of background genetic variation (pollinator, male-sterile, and interaction effects) to hybrid variation for nearly all characters measured, including seed size, than there was of the dwarfing gene. Selection of dwarf parents capable of producing hybrids with equal seed size and yield to that of tall parents should not be difficult. PMID- 24226458 TI - Production and meiotic analysis of autotriploid Triticum speltoides and T. bicorne. AB - Autotriploid Triticum speltoides and T. bicorne (2n=3x=21) were produced by pollinating autotetraploids with pollen from their respective diploids. The autotriploid plants were vigorous, male sterile, and morphologically resembled their diploid parents. At meiosis, T. speltoides (3x) averaged 2.52 univalents, 0.42 rod bivalents, 2.03 ring bivalents, 4.48 trivalents, and 0.03 chain quadrivalents per cell, and T. bicorne (3x) had 2.30 univalents, 0.20 rod bivalents, 2.10 ring bivalents, and 4.70 trivalents. Panhandle trivalents made up 27% of the total trivalents, and involved 18% of the total number of chromosomes observed in T. bicorne (3x), and 26% and 17% in T. speltoides (3x), respectively. The observed chromosome pairing in both triploids was predicted well from the expressions developed by Alonso and Kimber. PMID- 24226459 TI - Allozyme evidence for the origin and diversification of Gossypium barbadense L. AB - Gossypium barbadense L. is a commercially important cotton species of tropical South American origin presently grownin many regions of the world. The species is morphologically diverse, consisting of a wide range of wild (or feral), commensal, landrace, and highly improvedcommercial forms. We performed allozyme analysis on 153 accessions representing the spectrum of G. barbadense diversityto ascertain the geographic origin of the species, its patterns of diffusion subsequent to domestication, and to reveal infraspecific relationships. Levels ofgenetic variation in G. barbadense are moderate. Of 59 loci scored, 24 were polymorphic, with a mean number of alleles perlocus of 1.69 and an average panmictic heterozygosity of 0.062. Principal component analysis revealed geographic clustering of accessions into six relativelydiscrete regions. Gene frequencies at many loci are significantly heterogeneous among these regions, with an average G STof 0.272. Northwestern South America contains the greatest genetic variability; we suggest that this region is the ancestral home of the species. The data indicate separate diffusion pathways from this region into Argentina-Paraguay and into eastern and northern South America east of the Andes. Caribbean Island and Central American forms appear to be derived from the latter. These diffusion pathways are in accordance with morphological evidence and historical record. In contrast to expectations based on geographic proximity, Pacific Island forms have their closest affinity to accessions from eastern South America. Advanced cultivated stocks seem largely derived from western Andean material, but also contain introgressed G. hirsutum germ plasm. Introgression was relatively high (22%-50% of accessions) in commercial stocks and in forms from Argentina-Paraguay and various Pacific Islands, but was conspicuously low or absent in material from Central America and the Caribbean, where commensal and commercial forms of both species are sympatric. PMID- 24226460 TI - Genetic changes from introgression of highland Mexican germ plasm into a Corn Belt Dent population of maize. AB - A backcross population (NZS1) of maize (Zea mays L.) was produced by crossing a highland Mexican population with the elite Corn Belt Dent synthetic AS3, and then by backcrossing to AS3. S1 lines, S2 lines, and S2 testcrosses with an elite tester were used to compare the means, correlations, genetic variances, and predicted gains from selection of NZS1 and AS3 for grain yield, grain moisture at harvest, root and stalk lodging in a cool, temperate environment in New Zealand. The S1 and S2 lines from NZS1 had lower mean grain yields, higher levels of root lodging and higher mean grain moistures than the S1 and S2 lines from AS3. Mean grain yields of testcrosses of NZS1 and AS3 were similar, but NZS1 testcrosses had higher levels of root lodging. Genotypic variances estimated from S1 and S2 lines were larger for grain yield and root lodging for NZS1, smaller for grain moisture, and similar for stalk lodging. Predicted gains from selection for grain yield using intrapopulation methods based on the additive-genetic variance were larger for NZS1, but predicted gains for testcross selection were similar for the two populations. Lines with high combining ability for grain yield and acceptable grain moisture in combination with the tester occurred in NZS1. Because of the higher additive-genetic variance and the occurrence of lines with high combining ability for grain yield, we concluded that populations including highland Mexican germ plasm should be valuable for recurrent selection programs in New Zealand and in other cool, temperate regions. PMID- 24226461 TI - Cybrids of Nicotiana tabacum and Petunia hybrida have an intergeneric mixture of chloroplasts from P. hybrida and mitochondria identical or similar to N. tabacum. AB - The mitochondrial genomes of cybrids of Nicotiana tabacum containing chloroplasts of Petunia hybrida were characterized by restriction endonuclease digestion and agarose gel electrophoresis. Cybrids that displayed normal growth and development contained mitochondrial DNA indistinguishable from N. tabacum mitochondrial DNA. Cybrids that displayed abnormal growth and development contained mitochondrial DNA that differed from N. tabacum either by possessing a few additional fragments, by lacking a few fragments, or both. In spite of these differences, the mitochondrial DNA of cybrids showing abnormal growth and development was much more similar to N. tabacum than to P. hybrida mitochondrial DNA. In those cybrids that contained P. hybrida chloroplasts and N. tabacum mitochondria, cotransfer of cytoplasmic organelles did not occur. Although P. hybrida chloroplasts can interact compatibly with the N. tabacum nucleus, no cybrids were found in which P. hybrida mitochondria coexisted with the N. tabacum nucleus. PMID- 24226462 TI - Double-stranded RNA and male sterility in rice. AB - Double-stranded RNA (dsRNA) was isolated from rice Oryza sativa ssp. japonica, but not from other subspecies. The dsRNA has been found in all of the examined cytoplasmic male-sterile (CMS) lines of BT (Chinsurah Boro II)-type rice, but was not detected in their companionate maintainer lines. It is uniquely and positivley correlated with the CMS trait in BT-type rice. Recently, the dsRNA was also found in a nuclear malesterile (NMS) rice, Nongken 58s, but was not found in its normal Nongken 58. The molecular weight of this dsRNA was estimated to be about 18 kb. Electron microscopic analysis reveals that it is linear snapped. The double strandedness of the RNA molecules was characterized by CF-11 cellulose column chromatography and nuclease treatments. It bound to CF-11 cellulose in the presence of 15% ethanol. It was sensitive to RNase A at low salt concentrations, but insensitive to DNase I, SI nuclease, and RNase A at high salt concentrations. The dsRNA was detected in both mitochondrial and cytoplasmic fractions. Dot-blot hybridization reveals that there is no sequence homology between this dsRNA and mtDNA, but there is homology between this dsRNA and nuclear genomic DNA. We have not been able to transmit this dsRNA to fertile rice. PMID- 24226463 TI - "Erussica", the intergeneric fertile somatic hybrid developed through protoplast fusion between Eruca sativa Lam. and Brassica juncea (L.) Czern. AB - Hypocotyl calli-derived protoplasts of two cultivars of Brassica juncea (2n=36), a major oil-seed crop, were fused with normal as well as gamma-irradiated mesophyll protoplasts of Eruca sativa (2n=22). The irradiation of the Eruca fusion partner increased the plating efficiency as well as the morphogenic potentiality of the fusion products over the normal fusion. Fertile plants could be regenerated from such fusion products. Analysis of 63 out of 181 plants regenerated showed that, indeed, 11 somatic hybrids (2n=58) and 10 partial somatic hybrids (chromosome number ranged between 50 and 56) had been obtained. Pollen viability (0%-82.9%) and seed set (0%-50%) of the hybrids indicated them to be useful for future studies. PMID- 24226464 TI - The effect of repeated cycles of selection on genetic variance, heritability, and response. AB - The genetic variance of a quantitative trait decreases under directional selection due to generation of linkage disequilibrium. After a few cycles of selection on individual phenotype, a limit is reached where there is no further reduction in the genetic variance. Bulmer's model is extended to an animal breeding situation where selection is on information on relatives rather than on the individual's own performance. Algebraic expressions are derived to predict the decrease in genetic variance and associated reductions in heritability and response in the limit. Consequences of the results are discussed in the context of breeding strategies. PMID- 24226465 TI - Reverse Fox test for detecting visuospatial dysfunction corresponding to parietal hypoperfusion in mild Alzheimer's disease. AB - BACKGROUND/AIM: We developed a novel visuospatial clinical task to detect parietal dysfunction in mild Alzheimer's disease (AD). METHODS: A total of 65 outpatients, including 47 with mild AD and 18 cognitively and neuroradiologically normal individuals with subjective memory impairment (NL), performed the "Reverse Fox" test and underwent brain single photon emission tomography. Patients with AD were divided into subgroups according to the results of the Reverse Fox test (successful vs unsuccessful). RESULTS: Success in the Reverse Fox test was achieved by 31.9% of patients with AD and 94.4% of NL. The unsuccessful AD subgroup had reduced perfusion of the medial parietal and bilateral temporoparietal regions compared with the successful AD subgroup. CONCLUSIONS: Failure in the Reverse Fox test was related to parietal hypoperfusion in patients with mild AD. Our findings suggest that the Reverse Fox test may be one of the useful supporting tools for detecting mild AD at outpatient clinic. PMID- 24226466 TI - NAD(+)-linked isocitrate dehydrogenase in fish tissues. AB - NAD(+)-linked isocitrate dehydrogenase was found in the brain, heart, gills, kidney, liver and muscle of trout, and in the liver and muscle of eel. A complex homogenization buffer containing 1 mM ADP, 5 mM MgSO4, 5 mM citrate and 40% glycerol is required for retrieval of significant amounts of stable enzyme. The highest activities were found in brain of trout and the lowest in white muscle of trout and eel. The enzyme was partially purified from frozen trout heart to a final activity of 0.04 MUM/min/mg protein, and the kinetic properties of this partially purified enzyme were studied. The enzyme requires either Mn(2+) or Mg(2+) for activity, higher activities being observed with Mn(2+). Saturation kinetics for DL-isocitrate were sigmoidal, apparent S0.5=8.2+/-0.6 mM and nH=1.8+/-0.2, in the absence of ADP, changing to hyperbolic, apparent S0.5=1.4+/ 0.3 mM and nH=1.0, with 1 mM ADP added. Citrate and Ca(2+) were found to activate the enzyme to a small extent. NADH strongly inhibited the enzyme, I50=3.7+/-0.5 MUM. ATP was also found to be an inhibitor, I50=7.2+/-1.4 mM. These properties are consistent with the role of the enzyme as a major control site of the tricarboxylic acid cycle. PMID- 24226467 TI - Interacting effects of diet and environmental temperature on biochemical parameters in the liver ofLeuciscus idus melanotus (Cyprinidae: Teleostei). AB - One year old golden ide (Leuciscus idus melanotus) were starved for 2 weeks at 20 degrees C (time zero) and then they were fed either freeze-dried mosquito larvae (natural diet) or a commercial fish chow (artificial diet) at an ambient temperature of 14 degrees C and 20 degrees C, respectively. Growth parameters and biochemical data in the liver were measured at time zero and after 3 and 7 weeks of specific regimen. If compared to natural food, the artificial diet caused transient increase in anabolic activity of the liver, but prevented long-lasting hepatocyte proliferation (increase of total liver DNA). After 3 weeks on artificial diet, the body weight was significantly higher and the liver mass doubled compared to ide kept on the natural regimen; tissue DNA content indicated that the hepatocyte volume increased mainly by increased protein content and corresponding uptake of water; lipid and glycogen contents were increased by a factor of 3-6, and the RNA?DNA ratio was increased accordingly. The growth of the ide, as reflected by the condition factor and hepatosomatic index (HSI), was virtually stopped when the artificial regimen was maintained for 7 weeks, whereas on natural food the condition factor was increased and liver weight and DNA were doubled. Growth of the fish maintained at 14 degrees C was significantly lower than that of fish maintained at 20 degrees C, though the total liver DNA was still increased on the natural regimen during the experiment. Less lipid was stored by fish maintained at 14 degrees C, whereas protein and glycogen deposits were enlarged, if compared to fish maintained at 20 degrees C. The specific activity of cytochrome oxidase in liver mitochondria and of NADPH cytochrome c reductase in the microsomal fraction were found independent of diet and ambient temperature. Oxidative capacity of hepatocytes (mitochondrial protein/mg DNA) remained unchanged, and microsomal protein/cell appeared reduced in response to the artificial food. However, reduction of cell number on this diet resulted in less total mitochondrial and microsomal protein in the organ. Golden ide liver is found to be a sensitive experimental model to characterize the mutual influence of diet and temperature on fish; the results are discussed with regard to the usage of golden ide as test fish for water pollution. PMID- 24226468 TI - Relationship between transmembrane potential and activation of motility in rainbow trout (Salmo gairdneri). AB - A hypothesis is developed that activation of motility in rainbow trout spermatozoa is a result of membrane hyperpolarization. This hypothesis was developed to explain experimental observations of a relationship between membrane potential and motility as revealed by the use of voltage sensitive fluorescent dyes. The results lead to the following conclusions: a) Transmembrane potential hyperpolarizes with decreasing KCl concentration in 100 mM NaCl. b) Transmembrane potential hyperpolarizes with decreasing NaCl concentration. c) NaCl is three time less effective in changing transmembrane potential and two orders of magnitude less effective in inhibiting activation of motility than KCl. d) Chloride ions have little effect on transmembrane potential or motility. e) Increases in osmotic pressure with the non-ionic molecule sucrose increased the amount of KCl required to inhibit activation. f) The major effect of Na(+) on K(+) inhibition may be osmotic.It is suggested that while sperm cells are in the seminal plasma in the reproductive tract of the male rainbow trout their transmembrane potential is maintained above an activation threshold, probably through Na/K pumps which are found in almost all animal cells. Since K(+) is the most important ion in determining the transmembrane potential, hyperpolarization of the plasma membrane below an activation threshold occurs when the sperm cells are diluted, during spawning, into the low K(+) environment of freshwater. PMID- 24226469 TI - Characterization of transport Na(+)-ATPases in gills of freshwater tilapia : Evidence for branchial Na(+)/H (+) (-NH4 (+)), ATPase activity in fish gills. AB - Branchial plasma membranes from the freshwater cichlid teleostOreochromis mossambicus (tilapia) contain two Na(+)-dependent ATPases: Na(+)/K(+) ATPase, and an amiloride-sensitive ATPase which is postulated to operate as a Na(+)/H(+) ( NH4 (+)) ATPase. It is suggested that both enzyme activities are located in the basolateral membrane system of the chloride cells. K(+) has opposing effects on the two enzymes: it stimulates Na(+)/K(+) ATPase and inhibits Na(+)/H(+) (-NH4 (+)) ATPase activity. Na(+)/H(+) ATPase appears more sensitive to NH4 (+) at low concentrations than Na(+)/K(+) ATPase and the stimulatory effect by NH4 (+) ions on the first enzyme could be important in facilitating NH4 (+) excretion by tilapia gills under physiological conditions.In vitro maximum stimulation by NH4 (+) is similar for the two enzymes (200%). In contrast to Na(+)/K(+) ATPase, Na(+)/H(+) ATPase activity is inhibited by supra-physiological (>20 mM) concentrations of NH4 (+). PMID- 24226470 TI - Smoltification in steelhead trout (Salmo gairdneri): Developmental aspects of plasma constituents. AB - Selected biochemical parameters were measured in the plasma of both underyearling anadromous steelhead trout (Salmo gairdneri) and underyearling residentS. gairdneri. The analyses were conducted in an effort to determine whether or not there might be changes which could be associated with the parr-smolt transformation of anadromous strains. Plasma NH(+) 4 and plasma Na(+) were assayed and plasma proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE).Ammonia was the only plasma ion to show changes with time that were different between the two strains of fish. Proteins prepared by 2D PAGE exhibited developmental changes in both migratory and nonmigratory fish. Each strain exhibited changes with time and the anadromous fish displayed patterns of proteins that were not observed in the nonanadromous strain. It is possible that certain changes in the protein constituents found in anadromous fish are associated with the processes of smoltification. The data are consistent with the notion that this developmental event occurs over an extended period of time and is not restricted to the spring.The data suggest that there may be some changes that occur in certain plasma constituents of migratory fish beginning in the fall and continuing into the spring. The data also indicate that certain ontogenetic events that are not associated with smoltification can be ascertained by analyses of plasma. PMID- 24226471 TI - Stopped-flow kinetic studies of the formation and disintegration of polyion complex micelles in aqueous solution. AB - The formation of soluble polyion complexes (PICs) from anionic block copolymers, poly(ethylene oxide)-b-poly(sodium 4-styrene sulfonate) (PEO-b-PSSNa) and cationic block copolymers, poly(ethylene oxide)-b-poly(quaternized 2-(dimethyl amino)ethyl methacrylate) (PEO-b-PQDMA) was investigated by fluorescence spectroscopy, laser light scattering (LLS), and stopped-flow light scattering. Colloidally stabilized dispersions could be obtained upon direct mixing of the aqueous solutions of these two block copolymers, which indicated the formation of core-shell nanostructures with the core consisting of interpolymer electrostatic complexes between PSSNa and PQDMA blocks and the corona of PEO block. Both LLS and fluorescence results revealed that the most compact complex micelles formed at the equal molar ratio of oppositely charged SSNa and QDMA residues. The kinetics of the assembly process was studied via stopped-flow upon direct mixing of the two polymer solutions. The complexation process between PEO-b-PQDMA and PEO-b-PSSNa was fast and could finish within seconds. Moreover, the relaxation process can only be detected at near equal SSNa to QDMA molar ratios. The relaxation curves can be well fitted by a double-exponential function, leading to a fast relaxation process related to the initial quasi-equilibrium complex formation and a slow process related to the pre-complex structure rearrangements to the final equilibrium complexes. Both stages are determined as second-order reactions and processed through a micelle fusion-fission mechanism. Fluorescence kinetic studies revealed that the neutralization of an oppositely charged polyion was too fast to be detected and should be completed within the stopped-flow dead time. Thermodynamic studies revealed that spontaneous complexation is entropy driven. Upon increasing the ionic strength of the solutions, the complexation processes became slower due to the decrease of entropy driving force. The PIC dissociation process was further studied and considered to consist of two competing processes: a second-order process depending on PIC concentration and a first-order process independent of the PIC concentration. PMID- 24226472 TI - Calcium chloride as a major component contributing to aphid resistance ofNicotiana benthamiana. AB - Substances with antiaphid activity were extracted from the leaf surface of aphid resistantN. benthamiana and purified. Sugar esters and diacyl glycerols were isolated from the chloroform extract, but only diacyl glycerols showed significant activity. However, the major activity was found in the water extract rather than in the chloroform extract. From the water extract calcium chloride was isolated as the most abundant active substance. Only calcium chloride showed significant activity among several calcium salts and chlorides of several metals that are abundant in plants. Calcium contents per unit area of leaf surface ofN. benthamiana and aphid-resistantN. gossei were almost equal to each other and 10 100 times higher than that of aphid-susceptibleN. tabacum. PMID- 24226473 TI - Relative importance of semiochemicals from first and second trophic levels in host foraging behavior ofAphidius ervi. AB - The responses of femaleAphidius ervi to odors from a host food plant (Vicia faba), host aphids (Acyrthosiphon pisum), nonhost aphids (Aphis fabae), and aphid plant complexes were investigated in a specially designed wind tunnel and a Y tube olfactometer. In single-target (no-choice) and two-target (dual-choice) experiments, plant volatiles played a crucial role in the host foraging behavior ofA. ervi. The odor from theA. pisum-plant complex elicited the strongest responses byA. ervi females, followed by the odor from plants previously damaged by the feeding ofA. pisum. There was a significantly weaker response to odor fromA. pisum in the absence of the plant and to undamaged plants. Similarly, mechanically damaged plants and plants infested with the nonhost aphidA. fabae did not elicit strong responses. A plant that had been damaged byA. pisum and subsequently washed with distilled water was as attractive as an unwashed, previously infested plant.Aphidius ervi probably overcomes the reliability detectability problem by selectively responding to herbivore-induced, volatile, semiochemical cues emitted by the first trophic level and by distinguishing between the volatiles induced by host and nonhost aphids. PMID- 24226474 TI - Electroantennogram activity from antennae ofCeratitis capitata (Wied.) to fresh orange airborne volatiles. AB - Twenty-six compounds have been identified from fresh orange airborne volatiles, the most abundant being limonene and alloaromadendrene. Ethyl- and butylhexanoates were found in middle concentrations, whereas the other compounds occur at low levels. Electroantennograms recorded fromCeratitis capitata Wied. (males and females) revealed limonene. butyl hexanoate, dihydrocarvone, and limonene oxide to be most active. In the case of dihydrocarvone, 4-ethyl acetophenone, and carvone, female antennae give greater responses than antennae of males. Limonene oxide was more active for males than females. Total airborne volatiles recovered from oranges elicited high EAGs, with females being more sensitive than males. PMID- 24226475 TI - Quantitative comparison of volatile compounds among sevenMedicago spp. accessions. AB - Previous research identified the presence of unique semivolatile compounds in alfalfa weevil (Hypera postica Gyllenhal) (AW) -resistantMedicago accessions. These compounds may impart repellency to AW in alfalfa (Medicago sativa L.). The objective of our study was to analyze within- and between-population variation for four of these unique semivolatile compounds across eglandular and glandular hairedMedicago accessions. SevenMedicago accessions were evaluated under greenhouse conditions in an experiment arranged as randomized complete blocks with four replicates. Volatile compounds were extracted via supercritical fluid extraction and then quantitatively analyzed for levels of 2,7-dimethyl, 2,6 octadienol;cis-geraniol; 1,(E)-8,(Z)-10-tetradecatriene; and 1-hepten-3-ol. Significant difference (P<0.05) among entries were observed for 2,7-dimethyl,2,6 octadienol;cis-geraniol; 1, and (E)-8,(Z)-10-tetradecatriene. These compounds were found only in glandularhaired accessions. There were no significant differences in levels of 1-hepten-3-ol. Our findings demonstrate that the genetic incorporation of 2,7-dimethyl, 2,6-octadienol;cis-geraniol; 1, and (E)-8,(Z)-10 tetradecatriene into cultivated alfalfa will require interspecific crossing. Alfalfa weevil behavioral tests using these compounds must be conducted prior to such crosses in order to ascertain the efficacy of repellency by these compounds. PMID- 24226476 TI - Variation in aphid alarm pheromone content among glandular and eglandular hairedMedicago accessions. AB - Pea (Acyrthosiphon pisum Harris) and blue alfalfa aphid (A. kondoi Shinji) deterrency in alfalfa (Medicago saliva L.) may result from incorporating higher levels of the aphid alarm pheromone,(E)-beta-farnesene relative to(E)-beta caryophyllene. We evaluated five eglandular and two glandular-haired alfalfa accessions for differences in(E)-beta-farnesene and(E)-beta-caryophyllene content under glasshouse conditions using supercritical fluid extraction and gas chromatography. In addition, pea and blue alfalfa aphid olfactory behavioral tests were conducted uponMedicago species containing different ratios of(E)-beta famesene relative to(E)-beta-caryophyllene. No differences in(E)-beta caryophyllene content were observed among the seven entries (MU=0.42 ng/g plant material). Significant differences (P <= 0.05) among entries were observed for(E) beta-famesene content, with KS94GH6 exhibiting the highest (1.18 ng/g), and CUF 101 the lowest levels (0.35 ng/g). Elite tetraploid sources possessed significantly lower levels (MU=0.42 ng/g) of(E)-beta-farnesene than did wild and cultivated diploid accessions (MU=0.83 ng/g). Olfactory behavioral tests for both the pea and blue alfalfa aphids demonstrated KS94GH6 repelled aphids while cultivated alfalfa types attracted aphids in each case. Previously demonstrated aphid resistance in diploid KS94GH6 may result from superior(E)-beta- farnesene levels, but(E)-beta-farnesene is probably not a factor in cultivated alfalfa resistance. Finally, accession KS94GH6 could act as an excellent germplasm resource for the incorporation of higher(E)-beta-farnesene levels into cultivated alfalfa. PMID- 24226477 TI - Grain weevil,Sitophilus granarius (L.): Antennal and behavioral responses to male produced volatiles. AB - Coupled GC-EAG techniques have been applied to the study of volatiles from the grain weevil,Sitophilus granarius. for the first time. The size of EAG response was independent of the sex of the responding insect but was consistently larger to extracts of males than those of females. This difference was reflected in a behavioral preference for the male extracts by mated adults of both sexes tested together and virgin adults of both sexes tested separately. The GC-EAG results provide evidence for two materials that are released specifically by the males. Using circular dichroism. one has been found to be identical stereochemically with the (2S,3R)-sitophilate reported by others as the aggregation pheromone in a different strain. This enhances the prospects for the development of a single pheromone lure that would be generally applicable whatever the origin of the strain. The small amount of sitophilate found in the males suggests that it is not stored in large amounts. The other material, present in such a small amount that it has yet to be fully characterized, elicits a higher antennal activity than sitophilate and may have a significant role to play in enhancing the trap catch of this economically important pest. PMID- 24226478 TI - Hemicellulose is an important leaf-feeding resistance factor in corn to the fall armyworm. AB - The fall armyworm,Spodoptera frugiperda (J. E. Smith), (FAW) is a major pest of corn,Zea mays L., in the southeastern United States. The damage to pretassel corn is caused by larvae feeding primarily on immature inner whorls. In this study, resistant lines were found to contain more crude fiber in whorls, mostly hemicellulose and cellulose. While hemicellulose, chiefly an arabinoxylan, was higher in resistant (R) lines than in susceptible (S) lines, the distribution of constituent neutral sugars was very similar in the lines. Both lines also containedp-coumaric and ferulic acids. These phenolic acids are known to occur both in the free state and in the cell wall as complexes bound by ester linkages to the arabinose moiety of the arabinoxylan.(13)C NMR data showed that the intensity of the carbonyl carbon (184 ppm) in resistant hemicellulose was stronger, indicating a greater degree of cross-linking. Thus, resistant hemicellulose is both structurally different from susceptible hemicellulose and present in greater quantities. In two of three laboratory dietary tests, FAW larval weight gains were significantly higher on diets with (S) hemicellulose incorporated at the same level as (R) hemicellulose. Therefore, resistance to the FAW appears to be correlated with both a greater amount and a higher degree of cross-linking of the hemicellulose of (R) lines. PMID- 24226479 TI - Intra- and interindividual variation in flank gland secretions of free-ranging shrewsCrocidura russula. AB - Individual differences in flank gland secretions were examined among males of the monogamous shrewCrocidura russula during the breeding and nonbreeding seasons. Gas chromatography was used to measure intra- and interindividual variation of flank gland secretions of free-ranging shrews from different populations. The number of compounds detected by gas Chromatographic analyses was correlated with body mass, flank gland size, and the presence of blood parasites in individual shrews. Very few compounds were detected from the flank gland area of juvenile males. After they reached sexual maturity, however, the number of compounds detected from the flank gland secretions increased significantly. At the beginning of the reproductive season 48 different compounds were detected from male flank gland secretions. In the middle of the breeding season 70 compounds were detected, while only 11 compounds were detected during the nonbreeding season. Few compounds were common to all males. There were more volatile compounds in the flank gland secretions of males in the beginning of the breeding season than later in the breeding season. Males from the same population had fewer differences in the elution profile of compounds than males from different populations indicating that individuals from a distinct population have similar elution profiles of compounds and that each population has its own type of elution profile. No correlations were found between the number of compounds detected by gas chromatography for each male and the male's body mass or flank gland size. Blood parasites (trypanosomes,Trypanosoma crocidurae) were found in only three of 30 males investigated. PMID- 24226480 TI - Volatile compounds from interdigital gland of male white-tailed deer (Odocoileus virginianus). AB - Interdigital secretions were collected from eight male white-tailed deer of various ages. Analysis of volatiles was performed by gas chromatography-mass spectrometry with a modified headspace technique. Forty-six volatile compounds were found including alkanes, arenes, aldehydes, ketones, aliphatic acids, esters, pyrroles, furans, and sulfur compounds. Eleven occurred in higher concentrations (P<=0.10) in dominant (>=3.5-year-old) than in subordinate (>=1.5 year-old) animals. Dominant males typically have higher serum testosterone levels, and fatty acids and esters fluctuate with sebum production, which is under hormonal control. Therefore, these compounds may reflect testosterone levels and act as chemical signals indicating the presence of a dominant male. Interdigital volatiles also may act as generalized scent trail markers. PMID- 24226481 TI - Field attraction ofBiprorulus bibax Breddin (Hemiptera: Pentatomidae) to synthetic aggregation pheromone and (E)-2-hexenal, a pentatomid defense chemical. AB - A synthetic blend of the aggregation pheromone [(3R,4S,1'E)-3,4-bis(1' butenyl)tetrahydro-2-furanol, linalool, farnesol, and nerolidol] of the spined citrus bug,Biprorulus bibax, and the pentatomid defense chemical, (E)-2-hexenal, both attracted adultB. bibax to individual trees in citrus orchards. Lemon trees containing single glass vials with aggregation pheromone or (E)-2-hexenal were colonized by significantly greater numbers of reproductiveB. bibax than unbaited trees. There was no significant difference between the treatments and bug recruitment was not improved by using both treatments.B. bibax did not enter cylinder/funnel traps baited with aggregation pheromone but colonized trees containing the traps. Orange or lemon trees containing aggregation pheromone on orchard perimeters recruited significantly larger populations of emigrating, nonreproductiveB. bibax during fall than untreated trees. Nonreproductive bugs were not attracted to trees containing (E)-2-hexenal. The potential for using these semiochemicals as management tools forB. bibax is discussed. PMID- 24226482 TI - Avoidance response of a terrestrial salamander (Ambystoma macrodactylum) to chemical alarm cues. AB - Organisms from a wide variety of taxonomic groups possess chemical alarm cues that are important in mediating predator avoidance. However, little is known about the presence of such alarm cues in most amphibians, and in particular terrestrial salamanders. In this study we tested whether adult long-toed salamanders (Ambystoma macrodactylum) showed an avoidance response to stimuli from injured conspecifics. Avoidance of stimuli from injured conspecifics could represent avoidance of a chemical alarm cue or, alternatively, avoidance of a territorial pheromone or conspecific predator odor. Consequently, we also tested whether salamanders avoided stimuli from noninjured conspecifics. Salamanders avoided stimuli from injured but not from noninjured conspecifics. Therefore, we concluded that the response to injured conspecifics represents avoidance of a chemical alarm cue and not avoidance of a territorial pheromone or predator cue. This is the first clear demonstration of chemical alarm signaling by a terrestrial amphibian and the first report of chemical alarm signaling in an ambystomatid salamander. By avoiding an area containing stimuli from injured conspecifics, long-toed salamanders may lower their risk of predation by avoiding areas where predators are foraging. PMID- 24226483 TI - Factors affecting behavioral phase transition in the desert locust,Schistocerca gregaria (Forskal) (Orthoptera: Acrididae). AB - The behavior of the desert locust,Schistocerca gregaria (Forskal) (Orthoptera: Acrididae), is adjusted rapidly to population density and is a phase characteristic. We used discriminant analysis to quantify the extent of phase transition from the solitary to the gregarious phase and accurately classify the phase status on the basis of two decisive behavioral parameters: nymphal activity and social interaction. Fecal extracts. examined by olfactometry, attract solitarious nymphs but do not contribute to behavioral phase transition. Neither do visual stimuli alone. Short-range olfaction of airborne volatiles slightly affects behavioral phase transition. Antennectomy abolishes density response. Cuticular lipid extract, containing presumptive contact pheromones, does not attract nymphs, but does significantly affect behavioral phase transition. PMID- 24226484 TI - Hydration, ionic valence and cross-linking propensities of cations determine the stability of lipopolysaccharide (LPS) membranes. AB - The supra-molecular structure of LPS aggregates governs outer membrane permeability and activation of the host immune response during Gram-negative bacterial infections. Molecular dynamics simulations unveil at atomic resolution the subtle balance between cation hydration and cross-linking ability in modulating phase transitions of LPS membranes. PMID- 24226485 TI - Recent advances and contributions to procedural sedation with considerations for the future. AB - As the demand for sedation services have increased, the delivery of sedation has shifted from the operating room setting to areas distant to the operating room, both within and outside the hospital setting. Sedation delivery is not monopolized by any one specialty, but rather is being delivered by anesthesiologists as well as non-anesthesiologists. As the field of sedation burgeons and multi-specialists enter the realm of meeting the demands, so also have the politics increased. Unfortunately, the choice of sedative agents has not increased in parallel with the demand for sedation. Over the past decade, there has been a paucity of new introductions for procedural sedation. Rather, new formulations of approved agents are being reexamined. The safe, efficient and predictable delivery of sedation remains at the forefront of discussion and review worldwide. This review will explore the recent, significant and noteworthy contributions to the field of sedation. PMID- 24226486 TI - A pharmacokinetic study of 48-hour sevoflurane inhalation using a disposable delivery system (AnaConDa(r)) in ICU patients. AB - BACKGROUND: Little is known regarding sevoflurane kinetics and toxicity during long-term sedation of intensive care unit (ICU) patients using the AnaConDa(r) system. The objective of the present study was to establish a pharmacokinetic description of 48-h sevoflurane administration, and to estimate plasma concentrations of metabolites. METHODS: Forty-eight hour sedation with sevoflurane vaporized via an AnaConDa(r) device, with an end-tidal concentration objective of 1.5% (v/v), was initiated in 12 non-obese patients who did not have hepatic or renal failure but who required sedation for more than 48 h in our ICU. Plasma sevoflurane, hexafluoroisopropanol, and fluoride concentrations were determined over this time period and pharmacokinetic analysis was performed. RESULTS: The mean plasma concentration of sevoflurane was 76 mg/L at 24 h and 70 mg/L at 48 h. Wash-out of plasma sevoflurane correlated with a rapid decrease in the mean end-tidal sevoflurane level. The mean free plasma fraction of hexafluoroisopropanol never exceeded 8 mg/mL. The mean fluoride concentration was 0.8 umol/L on day 0, 51.7 umol/L on day 1, and 68.1 umol/L on day 2 (P<0.0001). The distribution volume was 53 L, the elimination constant 2.9 h-1, the transfer constant from compartment 1 to compartment 2 (K1-2) 1.2 h-1, the K2-1 0.26 h-1, the half-life of elimination 3.78 h, and the total clearance 156 L/h. CONCLUSION: Following 48 hours of sedation using sevoflurane inhalation administered using an AnaConDa(r) delivery device, sevoflurane washout was rapid. Plasma fluoride levels accumulated over the study period without apparent nephrotoxicity. PMID- 24226487 TI - Propofol versus thiopental by target controlled infusion in patients undergoing craniotomy. AB - BACKGROUND: For decades thiopental has been considered as the hypnotic drug of choice for intracranial surgery. However, total intravenous anesthesia performed with thiopental is associated with delayed recovery, whereas early post-operative neurological evaluation is critical. For this reason, target controlled infusion (TCI) of propofol is increasingly used for maintenance of anesthesia. However, a thiopental TCI has never been assessed for this purpose. We tested the hypothesis that a thiopental TCI provides an acceptable way to achieve early recovery compared to a propofol TCI during supratentorial surgery. METHODS: Eighty patients undergoing elective craniotomy for a supratentorial tumor were randomized to receive either a propofol TCI (group P) or a thiopental TCI (group T). Both groups received a sufentanil TCI and the bispectral index was monitored. The primary end-point was time to tracheal extubation. Secondary end-points were per- and post-operative hemodynamics as well as respiratory and recovery parameters. Assessment of study end-points was performed by an intensive care specialist blinded (like the patient) to the received hypnotic. RESULTS: Time to extubation was significantly (P<0.0001) shorter in group P (median 149 minutes; interquartile range 72-250 minutes) than in group T (median 453 minutes; interquartile range 286-813 minutes). Similarly, the recovery parameters were significantly better in group P than in group T. There was no difference between groups in terms of patient characteristics and hemodynamic parameters. CONCLUSION: Even with TCI and bispectral index monitoring, thiopental is associated with an inappropriate delayed recovery from supratentorial surgery compared to propofol TCI. PMID- 24226488 TI - Changes in thenar muscle tissue oxygen saturation assessed by near-infrared spectroscopy during weaning from mechanical ventilation. AB - BACKGROUND: Tissue oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) has been used to provide information on local tissue oxygenation in different clinical settings. This study aims to determine the effect of weaning from mechanical ventilation on thenar muscle StO2. METHODS: In consecutive critically ill mechanically ventilated patients, StO2 at the thenar eminence, along with a vascular occlusion test (VOT), were measured by NIRS, on mechanical ventilation and during a 2-hour T-piece spontaneous breathing trial (SBT). Hemodynamic, gas exchange and respiratory variables were recorded. RESULTS: Forty-four patients were included in this study, 25 tolerated the SBT and 19 failed. On mechanical ventilation, no differences in any measured variable were observed between patients who succeeded or failed. Two minutes after SBT start, StO2 was decreased in patients who failed whereas it did not change in patients who succeeded (P<0.001). For all data, 2 minutes after the start of SBT, StO2 significantly correlated with SaO2 (r=0.32, P=0.037) and with the respiratory frequency/tidal volume (f/VT) index (r=-0.34, P=0.023). VOT-derived StO2 downslope and StO2 upslope did not change significantly along the SBT test. The maximum StO2 value, its ratio to minimum StO2, and the post-VOT StO2 value decreased significantly in patients who failed whereas no change was found in those who succeeded the SBT (P=0.003, P=0.025 and P<0.001 respectively). StO2 and f/VT at the second minute of SBT yielded a receiver operator characteristics curve area value of 0.77 and 0.80, P=0.002, respectively, in detecting the SBT outcome. CONCLUSION: SBT failure was associated with a significant impairment of thenar muscle StO2. A decrease of StO2 at 2 minutes after disconnection from the ventilator was associated with SBT failure. Further validation is warranted. PMID- 24226489 TI - Immediate postoperative and mid-term survival in nonagenarians undergoing non traumatic emergency surgery. AB - BACKGROUND: Nonagenarian people are increasingly using the emergency services, however, few studies have addressed this population. The goal of this prospective observational study is to determine relevant factors that independently reduce their immediate postoperative and mid-term survival. METHODS: We included all the nonagenarians who underwent non-traumatic emergency surgery between 2006-2011. The dependent variable, days of postoperative survival, was studied at 2 intervals: 0-30 days and 31 days to 1 year after surgery (immediate and mid-term respectively). Firstly, we calculated the Kaplan-Meier survival curve (KMsc) of the whole population. To analyse the bivariate relationship between each of the pre-, intra-, and postoperative variables and mortality we used c2 and Fischer's test. Finally, we performed a stepwise Cox regression analysis and developed two models -one for each interval. RESULTS: The study included 142 patients. The overall one-year mortality rate was 47.2%, and the 30-day mortality rate was 35.9%. The KMsc showed a steep drop during the first month, and then a more gradual one for the rest of year. The inflection point was at day 26. The variables associated with a reduced immediate postoperative survival were neoplasms and 4 complications: heart failure, pulmonary aspiration, renal impairment and stroke. The factors associated with a reduced mid-term survival were: postoperative arrhythmia, surgical reintervention, and perioperative red blood cell transfusion. CONCLUSION: Postoperative complications are an important predictor of reduced survival both immediately, and in the mid-term. Furthermore, most postoperative mortality occurs within the first 26 days postsurgery; hence the need for an aggressive treatment of such complications during this period. PMID- 24226490 TI - Influence of LMA cuff pressure on the incidence of pharyngolaryngeal adverse effects and evaluation of the use of manometry during different ventilation modes: a randomized clinical trial. AB - BACKGROUND: Pharyngolaryngeal discomfort is a significant complication following the use of laryngeal mask airway (LMA). The present study aimed to investigate the relation of LMA cuff pressure and the occurrence of pharyngolaryngeal discomfort during spontaneous ventilation (SV), pressure support (PSV) and pressure control ventilation (PCV). METHODS: A hundred and twenty patients, ASA I III, were included in this study. Originally the patients were divided into three groups: the 1st group was left to breath spontaneously, the 2nd group was placed under PSV while PCV was used in the 3rd group. Each group was divided into two subgroups: A) intervention group (maintaining cuff pressure at 60 cmH2O, measurement in 10 min intervals) and B) observation group (no intervention in cuff pressure, measurement in 10 min intervals). Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane in air/oxygen. Patients were assessed 2 and 24 hours post-surgery, for sore throat, dysphonia or dysphagia. RESULTS: A and B subgroup comparison at 24 hours revealed a statistically significant difference in the presence of pharyngolaryngeal discomfort in the PSV group (10% versus 55% respectively, P=0.006). Furthermore, when assessing the effect of maintaining a constant cuff pressure regardless of mode of ventilation, significantly fewer adverse effects were observed (8.3% vs. 35%, P=0.001) when compared to the non-intervention subgroup. CONCLUSION: Maintaining LMA cuff pressure in values which do not exceed 60 cmH2O probably contributes in decreasing pharyngolaryngeal discomfort independently of ventilation mode. The ventilation mode which leads to the highest incidence of pharyngolaryngeal morbidity when cuff pressures are not closely monitored is PSV. PMID- 24226491 TI - Influence of apneic oxygenation and minimal tidal volumes on ventilator associated lung injury. AB - BACKGROUND: Protective tidal volumes such as 6 mL/kg can still result in tidal hyperinflation and expose the lung to mechanical stress. Further reduction of tidal volume and apneic oxygenation might mitigate lung injury. We aimed to assess the influence of minimal tidal volumes and apneic oxygenation in combination with arterio-venous extracorporeal lung assist (av-ECLA) on ventilator-associated lung injury. METHODS: Acute respiratory distress syndrome was induced in swine (N.=24) by saline lavage. The animals were randomized into three groups, ventilated in a pressure-controlled mode with a tidal volume (VT) of 6 mL/kg, 3 mL/kg and 0 mL/kg body weight, respectively. The latter two groups were instrumented with an av-ECLA device. Lung injury was assessed by histological examination of lung tissue at the end of the 24 hour experiment and by gas exchange parameters. RESULTS: Oxygenation was significantly lower in the 3 and 0 mL/kg groups, whereas CO2 remained in the targeted range in all groups. Histological examination revealed a reduction of tidal hyperinflation in the apical lung regions in the 3 and 0 mL/kg groups. In lower lung regions an increase of inflammation, intra-alveolar exudation and formation of atelectasis was shown in the animals ventilated with lower VTs. CONCLUSION: In combination with highly effective CO2-removal, the reduction of tidal volumes up to 0 mL was feasible. Tidal hyperinflation could be reduced in the upper lung areas, yet inflammation in the lower lung was higher with low tidal volumes. This stresses the differing mechanical properties of inhomogeneous injured lungs. PMID- 24226492 TI - Total intravenous anesthesia with superficial cervical block or morphine transition in patients undergoing carotid endarterectomy. AB - BACKGROUND: The aim of this study was compare the Aldrete score at 5 minutes of two groups of patients undergoing carotid endarterectomy with intravenous anesthesia, receiving either anesthetic superficial cervical plexus block or intravenous morphine as transition analgesia. METHODS: After Ethics Committee approval, this randomized, controlled, double-blind, single-center study was performed on patients undergoing carotid endarterectomy, who received total intravenous anesthesia with propofol and remifentanil infusion. After intubation, each patient was randomly assigned to Block (superficial cervical block with levobupivacaine before the surgical incision), or Morphine group (standardized dose of morphine 30 minutes before the end of surgery). In the recovery room, an investigator unaware of the patient randomization recorded time to extubation, Aldrete score, pain, nausea/vomiting, and shiver at T0 (time of extubation), and at 5 (T5), 10 (T10), and 30 minutes (T30) after extubation. RESULTS: Sixty-four patients were studied. Time to extubation was 11 +/- 6 min for Block and 20 +/- 10 min for Morphine group (P>0.001). Median Aldrete score at T0 was 9 in the Block and 6.5 in the Morphine group (P<0.001), at T5 it was 8.5 and 7.0 (P<0.001), respectively. At T5, 29 (90.6%) Block and 8 (25%) Morphine patients had an Aldrete score >= 8 (P<0.001). Systolic blood pressure was higher in the Block than in Morphine patients at T0 and T5. CONCLUSION: This study demonstrates shorter time to extubation and better emergence from anesthesia when total intravenous anesthesia is associated with superficial cervical block than with morphine as transition analgesia. PMID- 24226493 TI - Protective lung ventilation in operating room: a systematic review. AB - Postoperative pulmonary and extrapulmonary complications adversely affect clinical outcomes and healthcare utilization, so that prevention has become a measure of the quality of perioperative care. Mechanical ventilation is an essential support therapy to maintain adequate gas exchange during general anesthesia for surgery. Mechanical ventilation using high tidal volume (VT) (between 10 and 15 mL/kg) has been historically encouraged to prevent hypoxemia and atelectasis formation in anesthetized patients undergoing abdominal and thoracic surgery. However, there is accumulating evidence from both experimental and clinical studies that mechanical ventilation, especially the use of high VT and plateau pressure, may potentially aggravate or even initiate lung injury. Ventilator-associated lung injury can result from cyclic alveolar overdistension of non-dependent lung tissue, and repetitive opening and closing of dependent lung tissue resulting in ultrastructural damage at the junction of closed and open alveoli. Lung-protective ventilation, which refers to the use of lower VT and limited plateau pressure to minimize overdistension, and positive end expiratory pressure to prevent alveolar collapse at end-expiration, was shown to improve outcome in critically ill patients with acute respiratory distress syndrome (ARDS). It has been recently suggested that this approach might also be beneficial in a broader population, especially in critically ill patients without ARDS at the onset of mechanical ventilation. There is, however, little evidence regarding a potential beneficial effect of lung protective ventilation during surgery, especially in patients with healthy lungs. Although surgical patients are frequently exposed to much shorter periods of mechanical ventilation, this is an important gap in knowledge given the number of patients receiving mechanical ventilation in the operating room. This review developed the benefits of lung protective ventilation during surgery and general anesthesia and offers some recommendations for mechanical ventilation in the surgical context. PMID- 24226494 TI - Use of ETView Tracheoscopic Ventilation Tube(r) in airway management of a patient with tracheal injury. PMID- 24226495 TI - Comparison of unilateral and bilateral spinal anesthesia with 2% hyperbaric prilocaine in day-case inguinal herniorrhaphy: a randomized controlled trial. AB - BACKGROUND: Hyperbaric 2% prilocaine produces a faster onset and shorter duration of spinal anesthesia than a plain solution. The anesthetic profile could be improved by restricting the block to the operative side. We compared unilateral versus conventional bilateral spinal anesthesia with hyperbaric 2% prilocaine in day-case patients undergoing unilateral inguinal herniorrhaphy. METHODS: Eighty patients were randomly assigned to receive either conventional bilateral (N.=40) or unilateral (N.=40) spinal anesthesia with 50 mg hyperbaric prilocaine 2%. In the unilateral group, lateral decubitus was maintained for 10 minutes. Sensory and motor block courses, time to first micturition, and side effects were recorded. RESULTS: On the operated side, the highest sensory block was T8 (T12 T2) in the unilateral and T9 (T11-T4) in the bilateral group (P=0.0328); the time to motor (115 +/- 26 min in the unilateral and 108 +/- 24 min in the bilateral groups, P=0.2350) and sensory (156 +/- 30 min in the unilateral and 158 +/- 26 min in the bilateral groups, P=0.7550) block resolution was similar in both groups. On the non-operated side, the unilateral group had a faster motor (64 +/- 48, P<0.001) and sensory (120 +/- 47, P<0.001) time to block resolution than the conventional group. Restricted unilateral motor and sensory block was achieved in 30% and 12.5% of patients, respectively. Time to voiding was shorter in the unilateral than in the conventional group (220 +/- 47 vs. 249 +/- 51 min, respectively, P=0.0104). There were no significant differences in adequacy for surgery and side effects between the groups. CONCLUSION: In day-case inguinal herniorrhaphy, attempting unilateral spinal anesthesia with 50 mg hyperbaric 2% prilocaine produced faster time to voiding. PMID- 24226496 TI - Hypercapnic hypoventilation due to tracheobroncomalacia: the success of non invasive respiratory support with continuous positive airway pressure. PMID- 24226497 TI - The need to clot: a review of current management strategies for adverse bleeding events with new oral anticoagulants. AB - The new factor Xa inhibitors and direct thrombin inhibitors have offered alternatives to traditional anticoagulants, with benefits of no routine monitoring, less drug interactions, and oral administration. Current approved uses of these agents include prophylaxis of stroke in non-valvular atrial fibrillation and prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. However, concern over bleeding risk in the context of having no specific antidotes available is a topic of focus for many physicians in an acute care setting. This manuscript examines the recent literature in the management of acute bleeding and the various methods of reversing anticoagulation in this setting. Literature published over the last 18 months (2011/07/01 present) was gathered from PubMed, Ovid, and Medline under a combined search strategy covering bleeding, reversal, and new oral anticoagulants, both factor Xa and direct thrombin inhibitors. The use of prothrombin complex concentrate, fresh frozen plasma, activated recombinant factor VII, activated prothrombin complex concentrate, as well as adjuncts of charcoal, hemodialysis, and antifibrinolytics are discussed. Recommendations are based on the determination of the severity of the bleed and physiological markers of anticoagulation, and involve the use of prothrombin complex concentrate, activated recombinant factor VII, and adjunctive therapy as appropriate. PMID- 24226498 TI - Urine sodium profile in the course of septic acute kidney injury: insights relevant for kidney function monitoring. PMID- 24226499 TI - Which factors determine prognosis after ventilator-associated pneumothorax in mechanically ventilated patients? PMID- 24226500 TI - Oral fiberoptic intubation: the importance of the bevel orientation. PMID- 24226501 TI - High flow oxygen therapy: tracheal pressure and oxygenation relationships: still too much complex? PMID- 24226502 TI - Chest compressions for cardiac arrest: easier said than done... PMID- 24226503 TI - Hyponatremia: killer or innocent bystander? PMID- 24226504 TI - Assessing pain outcome: is oblique subcostal transversus abdominis plane block better than other techiques? PMID- 24226505 TI - Assessing association between postoperative hemoglobin levels and myocardial ischemic events. PMID- 24226506 TI - Vitamin C for preventing and treating tetanus. AB - BACKGROUND: Tetanus is a severe disease that can be prevented by vaccination. In developing countries vaccination coverage is not always high. Cases still occur also in developed countries, particularly in elderly people owing to their reduced immuno protection. There are about 1 million tetanus cases per year globally. In animal studies, vitamin C has protected against various infections and bacterial toxins. In a study with rats, vitamin C protected against the purified tetanus toxin. OBJECTIVES: To assess the prophylactic and therapeutic effect of vitamin C on tetanus. SEARCH METHODS: In May 2013 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations ); and Ovid EMBASE for this third update. SELECTION CRITERIA: Controlled trials of vitamin C as a prevention or treatment for tetanus, whether or not these were placebo controlled, in any language, published or unpublished. Two review authors independently made inclusion decisions. DATA COLLECTION AND ANALYSIS: Both review authors independently extracted data from trial reports and assessed methodological quality. Since one of the cells in a 2 * 2 table had no events, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for case fatality rate by using the Peto-method. Another of the 2 * 2 tables had no empty cells and the inverse-variance method was used to calculate its risk ratio (RR) estimate and 95% CI. We also used the Fisher's exact test to calculate the exact 95% CI for the OR of the 2 * 2 table with the empty cell. MAIN RESULTS: One single trial was eligible for inclusion. This non-randomised, unblinded, controlled trial undertaken in Bangladesh involved 117 tetanus patients. Vitamin C at a dosage of 1 g/day was administered intravenously alongside conventional treatment. At recruitment, the participants were stratified into two age groups and the results were reported by age. There was a significant difference in the vitamin C effect between the two age groups (P = 0.01). In the tetanus patients aged 1 to 12 years (n = 62), vitamin C treatment was associated with a 100% reduction in case fatality rate (95% CI from -100% to -94%). In patients aged 13 to 30 years (n = 55), vitamin C treatment was associated with a 45% reduction in case fatality rate (95% CI from -69% to -5%). AUTHORS' CONCLUSIONS: A single, non-randomised, poorly reported trial of vitamin C as a treatment for tetanus suggests a considerable reduction in mortality. However, concerns about trial quality mean that this result must be interpreted with caution and vitamin C cannot be recommended as a treatment for tetanus on the basis of this evidence. New trials should be carried out to examine the effect of vitamin C on tetanus treatment. PMID- 24226507 TI - Mechanistic investigations of test article-induced pancreatic toxicity at the endocrine-exocrine interface in the rat. AB - Pancreatic toxicity commonly affects the endocrine or exocrine pancreas. However, it can also occur at the endocrine-exocrine interface (EEI), where the capillary network of the islet merges with the capillaries of the surrounding acinar tissue, that is, the insulo-acinar portal system. The goal of this article is to describe a novel, test article-induced pancreatic toxicity that originated at the EEI and to summarize investigations into the mechanistic basis of the injury. This injury was initially characterized by light microscopy in 7/14 day-toxicity studies in Sprague-Dawley (Crl: CD(r)[SD]) rats with undisclosed test articles. Microvascular injury at the interface resulted in peri-islet serum exudation, fibrin deposition, hemorrhage, inflammation, and secondary degeneration/necrosis of surrounding exocrine tissue. More chronic injury presented as islet fibrosis and lobular atrophy. Direct cytotoxicity affecting the capillary endothelium at the EEI was confirmed ultrastructurally on day 4. Endothelial microparticle and blood flow studies further confirmed endothelial involvement. Similar lesions occurred less frequently in 2 other rat strains and not in the mouse, dog, or cynomolgus macaque. In summary, in vivo and investigative study data confirmed primary endothelial cytotoxicity in the pathogenesis of this lesion and suggested that the lesion may be rat/rat strain-specific and of uncertain relevance for human safety risk assessment. PMID- 24226508 TI - Concurrent and discriminant validity of the Star Excursion Balance Test for military personnel with lateral ankle sprain. AB - The Star Excursion Balance Test (SEBT) has frequently been used to measure motor control and residual functional deficits at different stages of recovery from lateral ankle sprain (LAS) in various populations. However, the validity of the measure used to characterize performance--the maximal reach distance (MRD) measured by visual estimation--is still unknown. OBJECTIVES: To evaluate the concurrent validity of the MRD in the SEBT estimated visually vs the MRD measured with a 3D motion-capture system and evaluate and compare the discriminant validity of 2 MRD-normalization methods (by height or by lower-limb length) in participants with or without LAS (n = 10 per group). RESULTS: There is a high concurrent validity and a good degree of accuracy between the visual estimation measurement and the MRD gold-standard measurement for both groups and under all conditions. The Cohen d ratios between groups and MANOVA products were higher when computed from MRD data normalized by height. CONCLUSION: The results support the concurrent validity of visual estimation of the MRD and the use of the SEBT to evaluate motor control. Moreover, normalization of MRD data by height appears to increase the discriminant validity of this test. PMID- 24226509 TI - NMR-based metabolomics and LC-MS/MS quantification reveal metal-specific tolerance and redox homeostasis in Chlorella vulgaris. AB - Live green algae are promising candidates for phytoremediation, but a suitable algal species which bio-accumulates high concentrations of heavy metals, and survives well in industrial water is yet to be identified. Potential metabolic engineering may be applied to improve algal phytoremediation performance, but the metal tolerance and bioaccumulation mechanisms in green algae have to be first fully understood. In this study, NMR-based metabolomics was used to study the effect of different metal species (copper, cadmium and lead) and metal concentrations in green microalgae, Chlorella vulgaris. High Cu concentrations influenced substantial decrease in organic osmolytes (betaine and glycerophosphocholine), which indicated Cu-induced redox imbalance. Accompanying redox imbalance, growth inhibition and photosynthesis impairments in Cu-spiked C. vulgaris revealed a clear relationship between Cu toxicity and redox homeostasis. As these metabolic changes were less prominent in Cd and Pb-spiked cultures, we inferred metal-specific toxicity in C. vulgaris, where redox active Cu(2+) is more potent than non-redox active Cd(2+) and Pb(2+) in causing redox imbalance. Subsequently, ICP-MS and LC-MS/MS quantification shed light on the metal-specific bioaccumulation and detoxification mechanisms. The metal bioconcentration factor (BCF) correlated well with the phytochelatin (PC) content in Cu and Cd-spiked C. vulgaris biomass. High BCF and PC levels with increasing Cu and Cd exposure concentrations indicated that PCs played a significant role in Cu and Cd bioaccumulation and detoxification. In contrast, the undetectable PC levels in Pb spiked cultures despite high Pb BCF suggest an alternative detoxification mechanism for Pb: either by passive absorption to the algal cell wall or interaction with glutathione (GSH). PMID- 24226510 TI - Competition between resonance ejection and ion dissociation during resonant excitation in a quadrupole ion trap. AB - The competition between ion dissociation and ion ejection during resonant excitation in a quadrupole ion trap is investigated. Ions of similar mass but with a range of critical energies for the onset of dissociation have been examined. The effects of the amplitude and duration of the resonant excitation, the well depth in which the ions are trapped, and the pressure and nature of the collision gas are explored. Once the onset of ion ejection is reached, the rate of ion ejection increases with increased amplitude of the resonant excitation signal. The rate of ejection decreases or stays constant as a function of the duration of the resonant excitation, depending upon the ion species being excited. Increasing the trapping well depth increases the relative amount of dissociation versus ejection as does increasing the pressure of the bath gas. Adding heavier bath gases lowers the onset of ion dissociation and raises the onset of ion ejection. PMID- 24226511 TI - Characterization of a high-pressure quadrupole collision cell for low-energy collision-indneed dissociation. AB - A RF-only quadrupole collision cell of new design has been evaluated for use in tandem mass spectrometry experiments as a component of a triple quadrupole mass spectrometer. The new design permits operation at values of collision gas thickness higher by 1 order of magnitude than those used in most cells of this type. When operated at sufficiently high collision gas pressures, the transmission efficiency for precursor ions increases with increasing pressure, often to values greater than those observed in the absence of collision gas. Simultaneously, the attainable resolving power for fragment ions across the entire mass-tocharge ratio range, even for multiply charged precursors, also increases to the point where isomers of a quadruply charged fragment are resolved. The performance of the cell, judged in terms of yields and resolution of fragment ions, has been investigated as a function of the nature and pressure of collision gas, the kinetic energy of the precursor ions that enter the cell, and of the size and charge state of the precursors. The enhanced performance is explicable in terms of a marked deceleration of all ions that emerge from the cell to very low energies, probably a few tens of millielectronvolts, so that the cell effectively acts as an ion source for the second mass filter (fragment ion analyzer) to provide a spectrum of ions of fixed axial energy. The high transmission efficiency appears to arise from a collisional focusing effect analogous to that exploited in three-dimensional RF ion traps. The low axial energies imply that ion transit times through the cell are sufficiently long (several milliseconds) that, in precursor ion experiments where the first mass filter is scanned, a hysteresis effect is observed. This implies that in this operating mode compromises must be sought between scan speed and quality of peak shape. Examples are given of spectra obtained under realistic operating conditions that employ flow injection of samples. PMID- 24226512 TI - Proton transfer reaction studies of multiply charged proteins in a high mass-to charge ratio quadrupole mass spectrometer. AB - Proton transfer reactions of multiply charged ions at high mass-to-charge ratios were explored with a low frequency quadrupole mass spectrometer. This instrument enabled a qualitative comparison of proton transfer reaction rates at low charge states for ions generated by electrospray ionization (ESI) from different solution conformations and for disulfide-linked versus disulfide-reduced protein ions. Proton transfer reactions that efficiently reduced the number of charges for ESI-generated ions to approximately the number of arginines in the polypeptide sequence were observed. No significant differences in gas-phase reaction rates were noted between different solution conformers. Differences in reaction rates between "native" and disulfide-reduced proteins were much smaller than those observed below m/z 2000 with lower proton affinity reagents or by using lower reagent concentrations. These smaller differences in reaction rates are thought to reflect the reduced electrostatic contributions from widely spaced charge sites and thus, the reduced sensitivi ty to an ion's three-dimensional structure or U compactness. PMID- 24226513 TI - Tandem mass spectrometry of poly(ethylene glycol) lithium-attachment ions. AB - A study of the fast-atom bombardment tandem mass spectrometry behavior of a number of ethylene glycol polymers (PEGs) has been carried out. Both linear (hydroxyl, amino, and/or alkyl end groups) and cyclic (crown ether) polymers were studied. One of the materials is a block copolymer of ethylene and propylene oxides. Collisional activation was carried out in the collision octapole of a BEoQ hybrid mass spectrometer at a translational energy of 50 eV, with collision gas air. For the linear polymers, the most intense product ions are lithiated, linear polyglycol oligomers, These ions are formed via internal hydrogen transfer reactions that are facilitated (charge-induced) by lithium. This series of product ions allows for the observation of consecutive losses of monomer units from the chain end; this is useful to determine the sequence of monomers in a copolymer. The most abundant product ions from cyclic PEGs are lithiated radical cations. An especially interesting finding in this work is the preferential loss of two internal ethylene oxide (EO) units (dioxane, 88 u) from some [M + Li](+) precursors. Factors that influence this loss include (a) the sequence length of EO repeat units in the oligomer and (b) the identity of the end groupts) on the oligomer. It is proposed that this elimination of dioxane involves a six-membered ring intermediate; this decomposition reaction is believed to be a lithium mediated (charge-induced) rearrangement. PMID- 24226514 TI - Dissociation characteristics of [M + X](+) ions (X = H, Li, Na, K) from linear and cyclic polyglycols. AB - The unimolecular reactions of protonated and metalated polyglycols with kiloelectronvolt translational energies have been studied by collisionally activated dissociation and neutralization-reionization mass spectrometry. The former method provides information on the ionic dissociation products, whereas the latter allows for the identification of the complementary neutral losses. Protonated linear polyglycols mainly undergo charge-initiated decompositions that lead to eliminations of smaller oligomers, On the other hand, protonated crown ethers ("cyclic" polyglycols) favor charge-induced reactions that proceed by cleavages of two ethylene oxide units in the form of 1,4-dioxane. Replacement of one O by NH in the crown ether dramatically changes its unimolecular chemistry; now, charge-remote 1,4-eliminations from ring-opened isomers are preferred. Charge-remote reactions are also the major decomposition channels of all metalated precursors studied. The linear polyglycols decompose primarily by 1,4 H2 eliminations and to a lesser extent by homolytic cleavages near chain ends. The reverse is true for metalated crown ethers, which preferentially produce distonic radical cations by the loss of saturated radicals; these reactions are proposed to involve prior rearrangement to open-chain isomers. The nature of the metal ion (Li(+), Na(+), or K(+)) does not greatly affect the unimolecular chemistry of the cationized polyglycol. In general, metalated precursors form many abundant fragment ions over the entire mass range; hence, collisional activation of such ions at high kinetic energy should be particularly useful for structure elucidations. PMID- 24226515 TI - Internal energy distributions of tungsten hexacarbonyl ions after neutralization Reionization. AB - The internal energy distributions P(epsilon) transferred to W(CO) 6 (+.) during the kiloelectronvolt collisions that occur upon neutralization-reionization (NR) have been estimated based on the relative abundances of the W(CO) 0-6 (+.) products present in NR spectra (thermochemical method). The average internal energy of the incipient {W(CO) 6 (+.) }(*) ions arising after near thermoneutral neutralization with trimethylamine followed by reionization with O2 is ~9 eV for 8-keV precursor ions and is mainly deposited during reionization, For comparison, the mean internal energy of {W(CO) 6 (+.) }(*) after electron ionization (EO or collisionally activated dissociation (CAD) is ~ 6 eV. Making the neutralization step endothermic slightly increases the overall excitation gained; however, a large increase in endothermicity (> 16 eV) causes only a modest rise of the average internal energy (<2 eV). The P(epsilon) curve for NR increases exponentially up to ~ 6 eV and levels off at higher energies.. showing that the probability of imparting large internal energies (6-17 eV) is high. In sharp contrast, the most probable excitation on CAD is <=6 eV, and the probability of deposition of larger energies declines exponentially. The mean internal energies after CAD and NR decrease steadily when the kinetic energy is lowered. The structure (minima-maxima) observed in the P(epsilon) distribution for El, which most likely originates from Franck-Condon factors, is not reproduced in the distributions for NR or high energy CAD, despite the fact that all three methods involve electronic excitation. Because of the large internal energies transferred upon NR, NR mass spectrometry could be particularly useful in the differentiation of ionic isomers with high dissociation but low isomerization thresholds. PMID- 24226516 TI - Elimination of methane from protonated acetaldehyde: The Ab initio transition state. AB - The transition state (TS) for loss of CH4 from protonated acetaldehyde has been located at the second-order Moller-Plesset (MP2)/6-31G(d, p) level of theory. The activation energy is predicted to be 263.9 kJ/mol starting from the more stable form (methyl and hydrogen E) and 261.6 kJ/mol starting from the less stable form (methyl and hydrogen Z) that is required for reaction. The products (methane and the formyl ion) are predicted to lie 136.6 kJ/mol below the TS for their formation. MP2 methods underestimate the heats of formation of both the TS and the reaction products by about 40 kJ/mol when compared with experiment. Restricted Hartree-Fock (RHF) calculations give much more accurate relative energies. The MP2 TS leads directly to fragmentation and is described as a protonation of the methyl group by the acidic proton on oxygen. Under RHF theory the reaction is stepwise. An RHF TS similar to the MP2 TS leads to a nonclassical intermediate (which is stable at this level of theory) that has one of the C-H bonds protonated. This mechanism (protonation of an alkyl group) appears to be a general one for high energy 1,2 eliminations from organic cations. PMID- 24226517 TI - Nitric oxide-assisted atmospheric pressure corona discharge ionization for the analysis of automobile hydrocarbon emission species. AB - Nitric oxide reagent gas has been found to improve the sensitivity and robustness of the atmospheric pressure corona discharge ionization (APCDI) process. Sensitivity has been increased by a factor of 20-100, depending on the compound, over APCDI without nitric oxide. The robustness (defined as the sensitivity to matrix interferences) of APCDI in the presence of water has been improved by a factor of 3 over normal APCDI. These improvements are due in part to a modification of the commercial inlet system and ionization chamber that allows the chamber and sample gases to be heated to 100 and 350 degrees C, respectively. Nitric oxide was chosen as the reagent gas because of the variety and selectivity of its interaction with hydrocarbons with differing functional groups. Product ions of nitric oxide ionization and their subsequent tandem mass spectra are presented and discussed for selected alkanes; alkenes, alkylbenzenes, alcohols; aldehydes, and an ether. A tandem mass spectrometry (unique parent ion-daughter ion transition) method was developed to quantify compounds of specific interest in vehicle emissions. The absolute sensitivity for these compounds, under ideal conditions, was determined and ranges from 0.006 ppb for xylene (most sensitive) to 80 ppb for C8 (or larger) normal alkanes. Routine sensitivity for real-world samples was in the single parts per billion range for aromatic and olefinic species. Potential applications include the real-time, on-line monitoring of selected hydrocarbons in automobile exhaust. PMID- 24226518 TI - RBP-J in FOXD1+ renal stromal progenitors is crucial for the proper development and assembly of the kidney vasculature and glomerular mesangial cells. AB - The mechanisms underlying the establishment, development, and maintenance of the renal vasculature are poorly understood. Here, we propose that the transcription factor "recombination signal binding protein for immunoglobulin kappa J region" (RBP-J) plays a key role in the differentiation of the mural cells of the kidney arteries and arterioles, as well as the mesangial cells of the glomerulus. Deletion of RBP-J in renal stromal cells of the forkhead box D1 (FOXD1) lineage, which differentiate into all the mural cells of the kidney arterioles along with mesangial cells and pericytes, resulted in significant kidney abnormalities and mortality by day 30 postpartum (P30). In newborn mutant animals, we observed a decrease in the total number of arteries and arterioles, along with thinner vessel walls, and depletion of renin cells. Glomeruli displayed striking abnormalities, including a failure of FOXD1-descendent cells to populate the glomerulus, an absence of mesangial cells, and in some cases complete loss of glomerular interior structure and the development of aneurysms. By P30, the kidney malformations were accentuated by extensive secondary fibrosis and glomerulosclerosis. We conclude that RBP-J is essential for proper formation and maintenance of the kidney vasculature and glomeruli. PMID- 24226519 TI - Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. AB - In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ~3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40 50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1-/-) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1-/- vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1-/- vs. WT after 24 h (-33 vs. -11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 +/- 2% in WT and 17 +/- 2% in Sglt1-/-. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ~10-fold and reduced FGR to 44 +/- 3% in WT and to -1 +/- 3% in Sglt1-/-. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50-60% of filtered glucose is excreted. PMID- 24226520 TI - Impaired renal function and development in Belgrade rats. AB - Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ~50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID- 24226521 TI - Biomechanical regulation of cyclooxygenase-2 in the renal collecting duct. AB - High-dietary sodium (Na), a feature of the Western diet, requires the kidney to excrete ample Na to maintain homeostasis and prevent hypertension. High urinary flow rate, presumably, leads to an increase in fluid shear stress (FSS) and FSS mediated release of prostaglandin E2 (PGE2) by the cortical collecting duct (CCD) that enhances renal Na excretion. The pathways by which tubular flow biomechanically regulates PGE2 release and cyclooxygenase-2 (COX-2) expression are limited. We hypothesized that FSS, through stimulation of neutral sphingomyelinase (N-SM) activity, enhances COX-2 expression to boost Na excretion. To test this, inner medullary CD3 cells were exposed to FSS in vitro and mice were injected with isotonic saline in vivo to induce high tubular flow. In vitro, FSS induced N-SM activity and COX-2 protein expression in cells while inhibition of N-SM activity repressed FSS-induced COX-2 protein abundance. Moreover, the murine CCD expresses N-SM protein and, when mice are injected with isotonic saline to induce high tubular flow, renal immunodetectable COX-2 is induced. Urinary PGE2 (445 +/- 91 vs. 205 +/- 14 pg/ml; P < 0.05) and microdissected CCDs (135.8 +/- 21.7 vs. 65.8 +/- 11.0 pg.ml(-1).mm(-1) CCD; P < 0.05) from saline-injected mice generate more PGE2 than sham-injected controls, respectively. Incubation of CCDs with arachidonic acid and subsequent measurement of secreted PGE2 are a reflection of the PGE2 generating potential of the epithelia. CCDs isolated from polyuric mice doubled their PGE2 generating potential and this was due to induction of COX-2 activity/protein. Thus, high tubular flow and FSS induce COX-2 protein/activity to enhance PGE2 release and, presumably, effectuate Na excretion. PMID- 24226522 TI - ROS dependence of cyclooxygenase-2 induction in rats subjected to unilateral ureteral obstruction. AB - Oxidative stress resulting from unilateral ureteral obstruction (UUO) may be aggravated by increased production of ROS. Previous studies have demonstrated increased cyclooxygenase (COX)-2 expression in renal medullary interstitial cells (RMICs) in response to UUO. We investigated, both in vivo and in vitro, the role of ROS in the induction of COX-2 in rats subjected to UUO and in RMICs exposed to oxidative and mechanical stress. Rats subjected to 3-day UUO were treated with two mechanistically distinct antioxidants, the NADPH oxidase inhibitor diphenyleneiodonium (DPI) and the complex I inhibitor rotenone (ROT), to interfere with ROS production. We found that UUO-mediated induction of COX-2 in the inner medulla was attenuated by both antioxidants. In addition, DPI and ROT reduced tubular damage and oxidative stress after UUO. Moreover, mechanical stretch induced COX-2 and oxidative stress in RMICs. Likewise, RMICs exposed to H2O2 as an inducer of oxidative stress showed increased COX-2 expression and activity, both of which were reduced by DPI and ROT. Similarly, ROS production, which was increased after exposure of RMICs to H2O2, was also reduced by DPI and ROT. Furthermore, oxidative stress-induced phosphorylation of ERK1/2 and p38 was blocked by both antioxidants, and inhibition of ERK1/2 and p38 attenuated the induction of COX-2 in RMICs. Notably, COX-2 inhibitors further exacerbated the oxidative stress level in H2O2-exposed RMICs. We conclude that oxidative stress as a consequence of UUO stimulates COX-2 expression through the activation of multiple MAPKs and that the induction of COX-2 may exert a cytoprotective function in RMICs. PMID- 24226523 TI - Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling. AB - Kindlin-2 is an adaptor protein that contributes to renal tubulointerstitial fibrosis (TIF). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells was regarded as one of the key events in TIF. To determine whether kindlin 2 is involved in the EMT process, we investigated its regulation of EMT in human kidney tubular epithelial cells (TECs) and explored the underlying mechanism. In this study, we found that overexpression of kindlin-2 suppressed epithelial marker E-cadherin and increased the expression of fibronectin and the myofibroblast marker alpha-smooth muscle actin (SMA). Kindlin-2 significantly activated ERK1/2 and Akt, and inhibition of ERK1/2 or Akt reversed kindlin-2 induced EMT in human kidney TECs. Mechanistically, kindlin-2 interacted with Ras and son of sevenless (Sos)-1. Furthermore, overexpression of kindlin-2 increased Ras activation through recruiting Sos-1. Treatment with a Ras inhibitor markedly repressed kindlin-2-induced ERK1/2 and Akt activation, leading to restraint of EMT. We further demonstrated that knockdown of kindlin-2 inhibited EGF-induced Ras-Sos-1 interaction, resulting in reduction of Ras activation and suppression of EMT stimulated by EGF. Importantly, we found that depletion of kindlin-2 significantly inhibited activation of ERK1/2 and Akt signaling in mice with unilateral ureteral obstruction. We conclude that kindlin-2, through activating Ras and the downstream ERK1/2 and Akt signaling pathways, plays an important role in regulating renal tubular EMT and could be a potential therapeutic target for the treatment of fibrotic kidney diseases. PMID- 24226525 TI - The fire within: pyroptosis in the kidney. PMID- 24226524 TI - SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. AB - Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60-80 mg.kg(-1).day(-1)) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38-56%) and reduced the expression of SGLT1 (by 33 37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187 237 vs. 517-535 mg/dl in vehicle group; 100-140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 MUl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 MUl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG. PMID- 24226526 TI - Tuberous sclerosis complex, mTOR, and the kidney: report of an NIDDK-sponsored workshop. AB - Remarkable basic and translational advances have elucidated the role of the mammalian target of rapamycin (mTOR) signaling network in the pathogenesis of renal disease. Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC), leading to one of the clearest therapeutic opportunities to target mTOR with rapamycin and its analogs ("rapalogs"), which effectively inhibit mTOR complex 1 (mTORC1) by an allosteric mechanism. Clinical trials based on these discoveries have provided strongly positive therapeutic results in TSC (Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN. N Engl J Med 358: 140-151, 2008; Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. N Engl J Med 363: 1801-1811, 2010; McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC. N Engl J Med 364: 1595-1606, 2011). In June 2013, the National Institute of Diabetes and Digestive and Kidney Diseases convened a small panel of physicians and scientists working in the field to identify key unknowns and define possible "next steps" in advancing understanding of TSC- and mTOR-dependent renal phenotypes. TSC-associated renal disease, which affects >85% of TSC patients, and was a major topic of discussion, focused on angiomyolipomas and epithelial cysts. The third major topic was the role of mTOR and mTOR inhibition in the pathogenesis and therapy of chronic renal disease. Renal cell carcinoma, while recognized as a manifestation of TSC that occurs in a small fraction of patients, was not the primary focus of this workshop and thus was omitted from panel discussions and from this report. PMID- 24226527 TI - Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis. AB - Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short-hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt, and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling and annexin V/propidium iodide staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis. PMID- 24226528 TI - Neuropsychological rehabilitation after brain injury: Scientific and professional issues. AB - Neuropsychological rehabilitation after acquired brain injury is an important contribution to our health-care system. Despite a growing database which supports its clinical utility, the insurance coverage for this form of care is now being threatened. This paper addresses some of the professional and scientific issues that psychologists need to face in order to continue to provide these services. PMID- 24226529 TI - Differential diagnosis of steroid-dependent nephrotic syndrome with psychosis: Practical and ethical issues. AB - The present case illustrates practical and ethical issues that can be encountered by clinical psychologists providing consultation services in medical settings. The neuropsychological consultation service was asked to evaluate a 22-year-old male with psychosis, steroid-dependent nephrotic syndrome, and a family history of schizophrenia. MRI revealedmarked cortical atrophy. Clinical findings were consistent with (1) steroid inducedapparent atrophy, which has been shown to be reversible with withdrawal of steroids; (2) uremia secondary to steroid withdrawal; (3) cortical atrophy, found in some schizophrenics; or (4) an atypical, diffuse degenerative disorder. Clinical interview and psychological testing revealed significant thought disorder, prominent delusions, somatic hallucinations, and mood disturbance. Deterioration in social and academic functioning was also present. Except for impaired attention and concentration, neuropsychological evaluation showed no clear evidence of brain-based dysfunction. Further, neuropsychological results effectively ruled out a degenerative process and were not consistent with a steroid effects profile. A conclusive differential diagnosis of steroid induced psychosis versus severe psychopathology would require withdrawal from steroids and antipsychotics. In addition to the practical and ethical issues of withholding antipsychotics, steroid withdrawal would require either dialysis or renal transplant surgery. Decision making regarding dialysis dependency and the possibility of postsurgical psychosis secondary to true psychopathology were salient issues to both the patient and the treatment team. PMID- 24226530 TI - Understanding symptoms of medical frontal lobe disorder: A clinical case study. AB - A case of anterior communicating artery aneurysm with damage to inferior medial frontal areas (Brodmann areas 25, 32, 24-inferior) is presented. Four prominent deficits are discussed: (1) anterograde amnesia, (2) inert perseverative card sorting, (3) motor stereotypies, and (4) reduplicative paramnesia. These four deficits are discussed as negative or positive symptoms, related either to damage in inferior medial frontal (Brodmann areas 25, 32, 24-inferior) regions or release phenomena of superior medial frontal (Brodmann areas 6-medial and 24 superior) regions. It is concluded that the inferior and superior medial frontal regions act as opponent processors, with the inferior (B25, 32) area functioning to switch current mental set while the superior (B24-superior, 6-medial) region functions to maintain current mental set. Testable hypotheses about the opponent processor mechanism are suggested, as applied to neuropsychiatric disorders. PMID- 24226531 TI - The role of the clinical psychologist on a burn unit in a general teaching hospital. AB - This paper reviews the core skills that a clinical psychologist brings to a burn unit and suggests a model for optimal psychological management of burn patients, families, and staff. Recovery from a burn injury involves three stages that comprise (a) acute treatment of severe medical complications, (b) adjustment to hospitalization, and (c) long-term rehabilitation. Each stage contains numerous issues that the clinical psychologist should monitor and manage. Assessment of patients at risk, early intervention, and specialist management are highlighted as critical components of effective psychological management of burn injury in a multidisciplinary team context. PMID- 24226532 TI - Social desirability, perceived stress, and PACT ratings in lung transplant candidates: A preliminary investigation. AB - Some aspect of psychosocial criteria is commonly utilized by most transplant programs in assessing candidates' acceptability for transplantation. However, regardless of the assessment methodology, information obtained in pretransplant assessments may be limited given the evaluative nature of the assessment as well as the sensitive nature of the contents. Indeed, transplant candidates may present themselves in a favorable fashion, minimizing any negative traits or psychological dysfunction which they perceive might prevent transplantation. Unfortunately, there are limited data addressing the extent to which transplant candidates may present themselves in an overly positive light. This investigation surveys the prevalence of social desirability in lung transplant candidates as well as its association with self-reports of perceived stress. Further, the relationship between social desirability and interviewer ratings of transplant candidacy is examined. Subjects included 24 patients in end-stage organ failure being evaluated for lung transplant candidacy. Subjects completed the Perceived Stress Scale and a brief version of the Marlowe-Crowne Social Desirability Scale. Additionally, subjects were interviewer-rated on the Psychosocial Assessment of Candidates for Transplantation. Results indicate social desirability is a prevalent phenomenon in lung transplant candidates, with more than half of the sample scoring at or above the 84th percentile on the social desirability measure. Further, self-reports of perceived stress are moderately and inversely associated with social desirability (r=-.55,p <= .01). Social desirability was unrelated to interviewer-ratings of transplant candidates acceptability (r=.13,p <= .56). Future research might include larger samples of subjects, other organ transplant candidates, and more detailed assessments of symptom distress. PMID- 24226533 TI - The impact of defibrillator discharges on psychological functioning of implantable cardioverter defibrillator recipients. AB - A lag exists with respect to our understanding of the psychological demands and rehabilitation needs of individuals who have undergone implantable cardioverter defibrillator (ICD) implantation. The ICD is designed to transmit an electric shock to the heart to treat a potentially life-threatening arrhythmia. This study specifically examined the impact of defibrillator discharges on the psychological functioning of ICD recipients. A questionnaire was self-administered to 33 individuals who have been living with the ICD for at least 6 months. Results revealed that levels of anger and depression were significantly higher in those subjects who reported a lower discharge rate, while sense of well-being was significantly higher in those subjects who reported a greater discharge rate. Possible explanations for our findings were proposed as well as implications for clinical intervention were discussed. PMID- 24226534 TI - Sex differences in anger expression, depressed mood, and aggression in children and adolescents. AB - The current study examined anger expression styles and their relationship to levels of depressed mood and aggressive behavior in male and female children and adolescents. Measures of anger, anger expression, and depressed mood were collected from both children and their parents. Hierarchical multiple regressions revealed that anger expression significantly predicted sadness but not aggression for females, after accounting for age and anger level. Among males, anger expression was important in predicting aggression but not sadness, whereas age and anger level best predicted sadness. These results suggest that age, anger level, and anger expression may be risk factors for depression and aggression among children and adolescents. Sex appears to be an important factor in anger expression styles and related depression and aggressive behavior. PMID- 24226535 TI - Glyoxysomal citrate synthase from watermelon cotyledons: immunocytochemical localization and heterologous translation in Xenopus oocytes. AB - Glyoxysomal citrate synthase (gCS) was purified from crude extracts of watermelon (Citrullus vulgaris Schrad.) cotyledons, yielding a homogenous protein with a subunit MW of 48 kDa. The enzyme was selectively inhibited by 5,5'-dithiobis-(2 nitrobenzoic acid), allowing quantification in the presence of the mitochondrial isoenzyme (mCS). Differences were also observed with respect to inhibition by ATP (k i=2.6 mmol . l(-1) for gCS, k i=0.33 mmol . l(-1) for mCS). The antibodies prepared against gCS did not cross-react with mCS. The immunocytochemical localization of gCS by the indirect protein A-gold procedure was restricted to the glyoxysomal membrane or the peripheral matrix of glyoxysomes. Other compartments, e.g. the endoplasmic reticulum, were not labeled. Xenopus oocytes were used for the translation of watermelon polyadenylated RNA (poly(A)(+)RNA). A translation product with a MW of 51 kDa was immunoprecipitated by the anti-gCS antibodies. It was absent in controls without poly(A)(+)RNA or with preimmune serum. A similar translation product was also immunoprecipitated after cell-free synthesis of watermelon poly(A)(+)RNA in a reticulocyte system, in contrast to the in-vivo labeled gCS (48 kDa). It was concluded that gCS is synthesized as a higher-molecular-weight precursor. PMID- 24226536 TI - Photorespiratory metabolism and immunogold localization of photorespiratory enzymes in leaves of C3 and C 3-C 4 intermediate species of Moricandia. AB - Photorespiratory metabolism of the C3-C4 intermediate species Moricandia arvensis (L.) DC has been compared with that of the C3 species, Moricandia moricandioides (Boiss.) Heywood. Assays of glycollate oxidase (EC 1.1.3.1), glyoxylate aminotransferases (EC 2.6.1.4, EC 2.6.1.45) and hydroxypyruvate reductase (EC 1.1.1.29) indicate that the capacity for flux through the photorespiratory cycle is similar in both species. Immunogold labelling with monospecific antibodies was used to investigate the cellular locations of ribulose 1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39), glycollate oxidase, and glycine decarboxylase (EC 2.1.2.10) in leaves of the two species. Ribulose 1,5 bisphosphate carboxylase/oxygenase was confined to the stroma of chloroplasts and glycollate oxidase to the peroxisomes of all photosynthetic cells in leaves of both species. However, whereas glycine decarboxylase was present in the mitochondria of all photosynthetic cells in M. moricandioides, it was only found in the mitochondria of bundle-sheath cells in M. arvensis. We suggest that localized decarboxylation of glycine in the leaves of M. arvensis will lead to improved recapture of photorespired CO2 and hence a lower rate of photorespiration. PMID- 24226537 TI - The utilisation of fatty-acid substrates in triacylglycerol biosynthesis by tissue-slices of developing safflower (Carthamus tinctorius L.) and sunflower (Helianthus annuus L.) cotyledons. AB - Developing cotyledons of safflower (Carthamus tinctorius L.) and sunflower (Helianthus annuus L.) readily utilised exogenously supplied (14)C-labelled fatty acid substrates for the synthesis of triacylglycerols. The other major radioactive lipids were phosphatidylcholine and diacylglycerol. In safflower cotyledons, [(14)C]oleate was rapidly transferred to position 2 of sn phosphatidylcholine and concomitant with this was the appearance of radioactive linoleate. The linoleate was further utilised in the synthesis of diacyl- and triacyl-glycerol via the reactions of the so-called Kennedy pathway. Supplying [(14)C]linoleate, however, resulted in a more rapid labelling of the diacylglycerols than from [(14)C]oleate. In contrast, sunflower cotyledons readily utilised both labelled acyl substrates for rapid diacylglycerol formation as well as incorporation into position 2 of sn-phosphatidylcholine. In both species, however, [(14)C]palmitate largely entered sn-phosphatidylcholine at position 1 during triacylglycerol synthesis. The results support our previous in vitro observations with isolated microsomal membrane preparations that (i) the entry of oleate into position 2 of sn-phosphatidylcholine, via acyl exchange, for desaturation to linoleate is of major importance in regulating the level of polyunsaturated fatty acids available for triacylglycerol formation and (ii) Palmitate is largely excluded from position 2 of sn-phosphatidylcholine and enters this phospholipid at position 1 probably via the equilibration with diacylglycerol. Specie differences appear to exist between safflower and sunflower in relation to the relative importance of acyl exchange and the interconversion of diacylglycerol with phosphatidylcholine as mechanisms for the entry of oleate into the phospholipid for desaturation. PMID- 24226538 TI - Distribution of polyamines and their related catabolic enzyme in etiolated and light-grown leguminosae seedlings. AB - Diamine-oxidase (DAO; EC 1.4.3.6) activity and di-and polyamine levels were estimated along the epicotyl and root of light-grown and etiolated lentil (Lens culinaris Medicus) and pea (Pisum sativum L.) seedlings. The activity of DAO was higher in etiolated epicotyls than in lightgrown ones. In both species there was a positive correlation between DAO activity and the diamine (putrescine and cadaverine) levels along the whole epicotyl and root. Polyamine (spermine and spermidine) distribution seemed to be associated with the meristematic and elongating zone of the epicotyl and root. The physiological function of DAO is discussed in relation to its possible role in providing hydrogen peroxide to peroxidase-dependent reactions occurring in the cell wall. PMID- 24226539 TI - Ethanol production and toxicity in suspension-cultured carrot cells and embryos. AB - The process of carrot (Daucus carota L.) somatic embryogenesis is highly sensitive to exogenously added ethanol, since 5 mM ethanol inhibits this process by 50%, whereas the growth of proliferating carrot cells is inhibited to the same extent by 20 mM ethanol. This is consistent with the fact that proliferating cultures produce ethanol and release it into the medium at concentrations up to 20 mM, whereas embryogenic culture medium contains less than 1 mM ethanol. Data are presented showing the influence of cell density and 2,4-dichlorophenoxyacetic acid on ethanol production and on the presence of an alcohol-dehydrogenase (EC 1.1.1.1.) inactivator in carrot embryos. PMID- 24226540 TI - A monoclonal antibody to (S)-abscisic acid: its characterisation and use in a radioimmunoassay for measuring abscisic acid in crude extracts of cereal and lupin leaves. AB - A monoclonal antibody produced to abscisic acid (ABA) has been characterised and the development of a radioimmunoassay (RIA) for ABA using the antibody is described. The antibody had a high selectivity for the free acid of (S)-cis, trans-ABA. Using the antibody, ABA could be assayed reliably in the RIA over a range from 100 to 4000 pg (0.4 to 15 pmol) ABA per assay vial. As methanol and acetone affected ABA-antibody binding, water was used to extract ABA from leaves. Water was as effective as aqueous methanol and acetone in extracting the ABA present. Crude aqueous extracts of wheat, maize and lupin leaves could be analysed without serious interference from other immunoreactive material. This was shown by measuring the distribution of immunoreactivity in crude extracts separated by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), or by comparing the assay with physicochemical methods of analysis. Analysis of crude extracts by RIA and either, after TLC purification, by gas chromatography using an electron-capture detector or, after HPLC purification, by combined gas chromatography-mass spectrometry (GC-MS) gave very similar ABA concentrations in the initial leaf samples. However, RIA analysis of crude aqueous extracts of pea seeds resulted in considerable overestimation of the amount of ABA present. Determinations of ABA content by GC-MS and RIA were similar after pea seed extracts had been purified by HPLC. Although the RIA could not be used to analyse ABA in crude extracts of pea seeds, it is likely that crude extracts of leaves of several other species may be assayed successfully. PMID- 24226541 TI - Effect of nitrogen stress and abscisic acid on nitrate absorption and transport in barley and tomato. AB - The potential of barley (Hordeum vulgare L.) and tomato (Lycopersicon esculentum Mill.) roots for net NO 3 (-) absorption increased two-to five fold within 2 d of being deprived of NO 3 (-) supply. Nitrogen-starved barley roots continued to maintain a high potential for NO 3 (-) absorption, whereas NO 3 (-) absorption by tomato roots declined below control levels after 10 d of N starvation. When placed in a 0.2 mM NO 3 (-) solution, roots of both species transported more NO 3 (-) and total solutes to the xylem after 2 d of N starvation than did N sufficient controls. However, replenishment of root NO 3 (-) stores took precedence over NO 3 (-) transport to the xylem. Consequently, as N stress became more severe, transport of NO 3 (-) and total solutes to the xylem declined, relative to controls. Nitrogen stress caused an increase in hydraulic conductance (L p) and exudate volume (J v) in barley but decrased these parameters in tomato. Nitrogen stress had no significant effect upon abscisic acid (ABA) levels in roots of barley or flacca (a low-ABA mutant) tomato, but prevented an agerelated decline in ABA in wild-type tomato roots. Applied ABA had the same effect upon barley and upon the wild type and flacca tomatoes: L p and J v were increased, but NO 3 (-) absorption and NO 3 (-) flux to the xylem were either unaffected or sometimes inhibited. We conclude that ABA is not directly involved in the normal changes in NO 3 (-) absorption and transport that occur with N stress in barley and tomato, because (1) the root ABA level was either unaffected by N stress (barley and flacca tomato) or changed, after the greatest changes in NO 3 (-) absorption and transport and L p had been observed (wild-type tomato); (2) changes in NO 3 (-) absorption/transport characteristics either did not respond to applied ABA, or, if they did, they changed in the direction opposite to that predicted from changes in root ABA with N stress; and (3) the flacca tomato (which produces very little ABA in response to N stress) responded to N stress with very similar changes in NO 3 (-) transport to those observed in the wild type. PMID- 24226542 TI - Growth response of barley and tomato to nitrogen stress and its control by abscisic acid, water relations and photosynthesis. AB - Barley (Hordeum vulgare L.) and tomato Lycopersicon esculentum Mill.) were grown hydroponically and examined 2, 5, and 10 d after being deprived of nitrogen (N) supply. Leaf elongation rate declined in both species in response to N stress before there was any reduction in rate of dryweight accumulation. Changes in water transport to the shoot could not explain reduced leaf elongation in tomato because leaf water content and water potential were unaffected by N stress at the time leaf elongation began to decline. Tomato maintained its shoot water status in N-stressed plants, despite reduced water absorption per gram root, because the decline in root hydraulic conductance with N stress was matched by a decline in stomatal conductance. In barley the decline in leaf elongation coincided with a small (8%) decline in water content per unit area of young leaves; this decline occurred because root hydraulic conductance was reduced more strongly by N stress than was stomatal conductance. Nitrogen stress caused a rapid decline in tissue NO 3 (-) pools and in NO 3 (-) flux to the xylem, particularly in tomato which had smaller tissue NO 3 (-) reserves. Even in barley, tissue NO 3 (-) reserves were too small and were mobilized too slowly (60% in 2 d) to support maximal growth for more than a few hours. Organic N mobilized from old leaves provided an additional N source to support continued growth of N-stressed plants. Abscisic acid (ABA) levels increased in leaves of both species within 2 d in response to N stress. Addition of ABA to roots caused an increase in volume of xylem exudate but had no effect upon NO 3 (-) flux to the xylem. After leaf-elongation rate had been reduced by N stress, photosynthesis declined in both barley and tomato. This decline was associated with increased leaf ABA content, reduced stomatal conductance and a decrease in organic N content. We suggest that N stress reduces growth by several mechanisms operating on different time scales: (1) increased leaf ABA content causing reduced cell-wall extensibility and leaf elongation and (2) a more gradual decline in photosynthesis caused by ABA-induced stomatal closure and by a decrease in leaf organic N. PMID- 24226543 TI - Lectin-gene expression in pea (Pisum sativum L.) roots. AB - The expression of a lectin gene in pea (Pisum sativum L.) roots has been investigated using the copy DNA of a pea seed lectin as a probe. An mRNA which has the same size as the seed mRNA but which is about 4000 times less abundant has been detected in 21-d-old roots. The probe detected lectin expression as early as 4 d after sowing, with the highest level being reached at 10 d, i.e. just before nodulation. In later stages (16-d- and 21-d-old roots), expression was substantially decreased. The correlation between infection by Rhizobium leguminosarum and lectin expression in pea roots has been investigated by comparing root lectin mRNA levels in inoculated plants and in plants grown under conditions preventing nodulation. Neither growth in a nitrate concentration which inhibited nodulation nor growth in the absence of Rhizobium appreciably affected lectin expression in roots. PMID- 24226544 TI - The lithium-chloride-soluble cell-wall layers of Chlamydomonas reinhardii contain several immunologically related glycoproteins. AB - Cell-wall glycoproteins of the unicellular green alga Chlamydomonas reinhardii have been purified from LiCl extracts of intact cells by gel exclusion chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antibodies were raised against several polypeptide components isolated from the LiCl extracts. All these antibodies specifically reacted with the cell surface of formaldehyde-fixed cells. They showed cross-reactivity with the different antigens and were also reactive against some other polypeptides present in the LiCl extracts of intact wild-type cells as shown by double diffusion assays and immunoblot analyses. These antigens were largely missing in LiCl extracts from the cell-wall-deficient mutant CW-15. The pattern of immunologically related cell-wall polypeptides of C. reinhardii varied during the vegetative cell cycle and was found to be also dependent on the growth conditions. Dot-immunobinding assays on chemically modified cell-wall glycoproteins demonstrated differences between the various antibodies with respect to their specificities. Differences were observed especially with respect to their reactivities against chemically deglycosylated cell-wall polypeptides. Chemical deglycosylation generally reduced the binding of the different antibodies indicating that all these antibodies recognize carbohydrate side chains. Only two of these antibody preparations, raised against cell-wall glycoproteins of relative molecular mass 35 and 150 kilodaltons, were found to be strongly reactive against deglycosylated cell-wall polypeptides. When these antibodies were saturated with cell-wall-derived glycopeptides in order to abolish the binding to carbohydrate side chains, they still recognized the same cell-wall polypeptides as did the untreated antibodies. These findings indicate that the cross-reactivity of the different cell-wall polypeptides with the antibodies is not exclusively the consequence of similar glycosylation patterns but is also the result of the presence of similar structures within the non glycosylated stretches of the polypeptide backbones. Cell walls isolated from growing tobacco pollen tubes contained a single polypeptide component which showed crossreactivity with the antibodies to the cell-wall glycoproteins of C. reinhardii. PMID- 24226545 TI - Studies on the regulation of 1-aminocyclopropane-1-carboxylate synthase in tomato using monoclonal antibodies. AB - A partially purified preparation of 1-aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14) from tomato (Lycopersicon esculentum (Mill.) fruit tissue was used to generate monoclonal antibodies (MAb) specific for the two different MAbs yielded a 50-kDa polypeptide as shown by sodium dodecylsulfate polyacrylamide gel electrophoresis. An enzyme-linked immunosorbent assay (ELISA) capable of detecting <1 ng of antigen was developed. The ELISA system was used to demonstrate that two of the MAbs recognized different epitopes on the ACC synthase protein. Wound-induced increases in ACC-synthase activity in tomato fruit tissue were correlated with changes in ELISA-detectable protein. In-vivo labeling of wounded tissue with [(35)S]methionine followed by extraction and immunopurification in the presence of various protease inhibitors yielded one major radioactive band of 50 kDa molecular mass. Pulse labeling with [(35)S]methionine at various times after wounding indicated that the wound induced increase in ACC-synthase activity involved de-novo synthesis of a rapidly turning over 50-kDa polypeptide. PMID- 24226546 TI - Inhibition of light-induced stomatal opening and of guard-cell-protoplast swelling in Vicia faba L. by tentoxin, an inhibitor of photophosphorylation. AB - The fungal phytotoxin tentoxin and its natural derivative dihydrotentoxin impair light-induced stomatal opening in epidermal strips of broad bean (Vicia faba L.) incubated in a potassium-rich medium. Swelling of guard-cell protoplasts (GCPs) of the same species is inhibited in the presence of both substances. Swollen GCPs shrink after tentoxin or dihydrotentoxin treatment and these effects cannot be fully compensated by the phytoeffector fusicoccin. A comparison with the potassium carrier valinomycin shows that tentoxin acts in a different manner, because it is effective in the light only, whereas valinomycin causes shrinkage of GCPs also in the dark. Determination of adenine nucleotides in GCPs indicates a reduced ATP content and an enhanced ADP level after addition of tentoxin. At the same time, tentoxintreated GCPs contain more NADPH and less NAD(+) than the control (NADP(+) and NADH content does not differ). The results presented are consistent with the hypothesis that tentoxin closes stomata as a consequence of its inhibitory action on photophosphorylation. PMID- 24226547 TI - Xanthoxin levels and metabolism in the wild-type and wilty mutants of tomato. AB - Using (13)C-labelled internal standards and gas chromatography-mass spectrometry/multiple-ion monitoring the levels of xanthoxin (Xan) and 2-trans xanthoxin (t-Xan) have been determined in stressed and non-stressed leaves of wildtype tomato (Lycopersicon esculentum Mill cv. Ailsa Craig), and the wilty mutants, notabilis (not), flacca (flc) and sitiens (sit). Levels of Xan were very low in all tissues. Ratios of t-Xan: Xan ranged from 10:1 to <500:1. In the wild type and flc, t-Xan levels increased following stress. The results from feeding experiments using [(13)C]Xan and t-Xan demonstrated that whilst wild-type and not plants readily converted Xan into abscisic acid (ABA), flc and sit plants converted only a small amount of applied Xan into ABA. In all plants t-Xan was not converted into ABA. These results indicate that the flc and sit mutants are impaired in ABA biosynthesis because they are unable to convert Xan into ABA, whereas the not mutant is blocked at a metabolic step prior to Xan. Another possible ABA precursor, ABA-1',4'-trans-diol (ABA-t-diol) was found to occur in wild-type and mutant tissue. All four tissues could convert [(2)H]ABA-t-diol to ABA. Incubation of stressed leaves in the presence of (18)O2 provided evidence consistent with Xan and ABA originating via oxidative cleavage of a xanthophyll such as violaxanthin. PMID- 24226548 TI - Generation of hydroxyl radicals by soybean nodule leghaemoglobin. AB - Leghaemoglobin, a protein present in root nodules of soybean (Glycine max (L.) Merr.), generates the highly reactive hydroxyl radical (.OH) upon incubation with hydrogen peroxide (H2O2). The H2O2 appears to cause breakdown of the haem, releasing iron ions that convert H2O2 into .OH outside the protein. Oxyleghaemoglobin (oxygenated ferrous protein) is more sensitive to attack by H2O2 than is metleghaemoglobin (ferric protein). The possibility of oxyleghaemoglobin breakdown by H2O2 and formation of damaging .OH may explain why the root nodule is equipped with iron-storage proteins and enzymes that can remove H2O2. PMID- 24226549 TI - Incorporation of (14)CO 2 into C 4 acids by leaves of C 3-C 4 intermediate and C 3 species of Moricandia and Panicum at the CO 2 compensation concentration. AB - Comparative (14)CO2 pulse-(12)CO2 chase studies performed at CO2 compensation (Gamma)-versus air-concentrations of CO2 demonstrated a four-to eightfold increase in assimilation of (14)CO2 into the C4 acids malate and aspartate by leaves of the C3-C4 intermediate species Panicum milioides Nees ex Trin., P. decipiens Nees ex Trin., Moricandia arvensis (L.) DC., and M. spinosa Pomel at Gamma. Specifically, the distribution of (14)C in malate and aspartate following a 10-s pulse with (14)CO2 increases from 2% to 17% (P. milioides) and 4% to 16% (M. arvensis) when leaves are illuminated at the CO2 compensation concentration (20 MUl CO2/l, 21% O2) versus air (340 MUl CO2/l, 21% O2). Chasing recently incorporated (14)C for up to 5 min with (12)CO2 failed to show any substantial turnover of label in the C4 acids or in carbon-4 of malate. The C4-acid labeling patterns of leaves of the closely related C3 species, P. laxum Sw. and M. moricandioides (Boiss.) Heywood, were found to be relatively unresponsive to changes in pCO2 from air to Gamma. These data demonstrate that the C3-C4 intermediate species of Panicum and Moricandia possess an inherently greater capacity for CO2 assimilation via phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31) at the CO2 compensation concentration than closely related C3 species. However, even at Gamma, CO2 fixation by PEP carboxylase is minor compared to that via ribulosebisphosphate carboxylase (EC 4.1.1.39) and the C3 cycle, and it is, therefore, unlikely to contribute in a major way to the mechanism(s) facilitating reduced photorespiration in the C3-C4 intermediate species of Panicum and Moricandia. PMID- 24226550 TI - Variation in endoplasmic-reticulum-associated glycoproteins of carrot cells cultured in vitro. AB - Glycoproteins extracted from microsomes of in-vitro-cultured cells of Daucus carota L. cv. US-Harumakigosun were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and detected by peroxidase-conjugated concanavalin A. The appearance of a glycoprotein with Mr 31 000 (GP 31) was correlated with the ability of cells to form somatic embryos. GP 31 appeared in embryogenic cells cultured in 2,4-dichlorophenoxyacetic acid (2,4-D)-containing medium, but not in somatic embryos and non-embryogenic cells; it disappeared when the cultures were transferred to auxin-free medium. Another glycoprotein with Mr 32 000 (GP 32) was detected only in non-embryogenic cells, regardless of the presence or absence of 2,4-D. Both glycoproteins, GP 31 and GP 32, were associated with the rough endoplasmic reticulum and were extractable with 0.05% deoxycholate. PMID- 24226551 TI - Simultaneous influx of ammonium and potassium into maize roots: kinetics and interactions. AB - The interaction between ammonium and potassium during influx was examined in roots of dark-grown decapitated corn seedlings (Zea mays L., cv. Pioneer 3369A). Influx was measured during a 10-min exposure to either ((15)NH4)2SO4 ranging from 10 to 200 MUM NH 4 (+) with and without 200 MUM K((86)Rb)Cl or to K((86)Rb)Cl ranging from 10 to 200 MUM K(+) with and without 200 MUM NH 4 (+) as ((15)NH4)2SO4. The simple Michaelis-Menten model described the data well only for potassium influx in the presence of ambient ammonium. For the other three instances, the data were improved by assuming that a second influx mechanism became operative as the low-concentration phase approached saturation. Two distinct mechanisms are thus indicated for both ammonium and potassium influx within the range of 10 to 200 MUM.The influx mechanism operating at low concentrations showed greater affinity for potassium than for ammonium, even though the capacity for ammonium transport was twice as large as that for potassium. It is suggested that this phase involved a common transport system for the two ions and that localized low acidity next to the internal surface, following H(+) extrusion, favored ammonium deprotonation and dissociation from the transport system-ammonium complex. Parallel decreases in V max and increases in Km of the low-concentration saturable phase occurred for ammonium influx when ambient potassium was present and for potassium influx when ambient ammonium was present. The data support a mixed-type inhibition in each case. Simultaneous measurement of potassium and ammonium influx showed that they were highly negatively correlated at the lower concentrations, indicating that the extent to which influx of the inhibited ion was restricted was associated with influx of the inhibitor ion. Presence of ambient ammonium eliminated the second phase of potassium influx. In contrast, the presence of ambient potassium decreased the concentration at which the second phase of ammonium influx was initiated but did not restrict the rate. PMID- 24226552 TI - Effectively addressing addiction requires changing the language of addiction. AB - Public knowledge and attitudes about addiction are largely inconsistent with scientific evidence. The gap between the facts and public and professional perceptions is due in part to the language used to describe the disease and those who have it. A key step in modifying public attitudes and improving how health professionals and policymakers address addiction is to better align the language of addiction with the scientific evidence. Unless we clarify the language, those with the disease will continue to experience the stigma associated with it and attempts to deliver comprehensive and effective evidence-based prevention, treatment, and disease management will be profoundly compromised. PMID- 24226553 TI - Hinged circular fixator construct for correction of congenital metatarsal deformity in a foal. AB - A five-week-old American Quarter Horse colt was presented for evaluation of a left hindlimb deformity and lameness. Radiographs of the left hindlimb revealed a varus deformity with recurvatum originating in the mid-diaphysis of the third metatarsal bone. Surgical correction was undertaken by performing an osteotomy through the centre of rotation of angulation located within the mid-diaphysis of the third metatarsal bone, and a four-ring hinged circular external fixator construct was applied. Distraction of the osteotomy site was performed over an 11 day period. Notable complications included failure of a fixation pin, infection of the surgical site, and temporary laxity of the supporting tendons and ligaments of the contralateral metatarsophalangeal joint. The fixator was maintained until there was sufficient bone formation to allow frame removal, 152 days after the initial surgery. Use of a hinged circular construct allowed for partial correction of the deformity with resultant lengthening and resolution of the lameness in this colt. PMID- 24226554 TI - Functional outcomes for children with severe sepsis: is a "good save" good enough? PMID- 24226555 TI - Toward a restrictive transfusion practice in the PICU: if not now, when? if not us, who? PMID- 24226556 TI - Extracorporeal membrane oxygenation: a decade of progress, one patient at a time. PMID- 24226557 TI - Defining adequate pain control in the child with Down syndrome: are we treating perception or reality? PMID- 24226558 TI - Extracorporeal membrane oxygenation in resource-limited countries. PMID- 24226559 TI - Neuromonitoring of neonatal extracorporeal membrane oxygenation patients using serial cranial ultrasounds. PMID- 24226560 TI - Pediatric drug dosing during renal replacement therapy: searching for help. PMID- 24226561 TI - Optimizing fluid management in children on extracorporeal life support. PMID- 24226562 TI - Simulation-based procedural training for pediatric residents: one small step for a program ... one giant leap for mankind! PMID- 24226563 TI - The ventricular assist device: bridge to transplant. Bridge to recovery? Bridge to beyond? PMID- 24226564 TI - Pediatric risk of mortality: is it the time of admission or the disease? PMID- 24226565 TI - The author replies. PMID- 24226566 TI - Simulation training for pediatric residents on central venous catheter placement: a pilot study. AB - OBJECTIVE: To assess the effect of simulation training on pediatric residents' acquisition and retention of central venous catheter insertion skills. A secondary objective was to assess the effect of simulation training on self confidence to perform the procedure. DESIGN: Prospective observational pilot study. SETTING: Single university clinical simulation center. SUBJECTS: Pediatric residents, postgraduate years 1-3. INTERVENTIONS: Residents participated in a 60- to 90-minute ultrasound-guided central venous catheter simulation training session. Video recordings of residents performing simulated femoral central venous catheter insertions were made before (baseline), after, and at 3-month following training. Three blinded expert raters independently scored the performances using a 24-item checklist and 100-mm global rating scale. At each time point, residents rated their confidence to perform the procedure on a 100-mm scale. MEASUREMENTS AND MAIN RESULTS: Twenty-six residents completed the study. Compared with baseline, immediately following training, median checklist score (54.2% [interquartile range, 40.8-68.8%] vs 83.3% [interquartile range, 70.0 91.7%]), global rating score (8.0 mm [interquartile range, 0.0-64.3 mm] vs 79.5 mm [interquartile range, 16.3-91.7 mm]), success rate (38.5% vs 80.8%), and self confidence (8.0 mm [interquartile range, 3.8-19.0 mm] vs 52.0 mm [interquartile range, 43.5-66.5 mm]) all improved (p < 0.05 for all variables). Compared with baseline, median checklist score (54.2% [interquartile range, 40.8-68.8%] vs 54.2% [interquartile range, 45.8-80.4%], p = 0.47), global rating score (8.0 mm [interquartile range, 0.0-64.3 mm] vs 35.5 mm [interquartile range, 5.3-77.0], p = 0.62), and success rate (38.5% vs 65.4%, p = 0.35) were similar at 3-month follow-up. Self-confidence, however, remained above baseline at 3-month follow-up (8.0 mm [interquartile range, 3.8-19.0 mm] vs 61.0 mm [interquartile range, 31.5 71.8 mm], p < 0.01). CONCLUSIONS: Simulation training improved pediatric residents' central venous catheter insertion procedural skills. Decay in skills was found at 3-month follow-up. This suggests that simulation training for this procedure should occur in close temporal proximity to times when these skills would most likely be used clinically and that frequent refresher training might be beneficial to prevent skills decay. PMID- 24226567 TI - Imbalance between pulmonary angiotensin-converting enzyme and angiotensin converting enzyme 2 activity in acute respiratory distress syndrome. AB - OBJECTIVE: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter regulatory enzyme of angiotensin-converting enzyme that converts angiotensin II into angiotensin-(1-7). The aim of this study was to determine pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in patients with acute respiratory distress syndrome. DESIGN: Prospective observational pilot study. SETTING: A PICU of a university hospital. PATIENTS: Fourteen patients admitted, requiring mechanical ventilation for respiratory syncytial virus lower respiratory tract infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two groups of patients were distinguished at admission: a group fulfilling the criteria for acute respiratory distress syndrome and a non-acute respiratory distress syndrome group. Angiotensin converting enzyme and angiotensin-converting enzyme 2 activity were measured in bronchoalveolar lavage fluid. Patients with acute respiratory distress syndrome had increased angiotensin-converting enzyme activity and decreased angiotensin converting enzyme 2 activity (p < 0.001) compared with the control group. CONCLUSION: It is shown for the first time that in acute respiratory distress syndrome, enhanced angiotensin-converting enzyme activity is paralleled by a reduced angiotensin-converting enzyme 2 activity, similar to that found in an experimental rat model of acute respiratory distress syndrome. The reduced angiotensin-converting enzyme 2 activity may be counteracted by restoring angiotensin-(1-7) level, thereby offering a novel treatment modality for this syndrome. PMID- 24226568 TI - Clobetasol propionate, 0.05%, vs hydrocortisone, 1%, for alopecia areata in children: a randomized clinical trial. AB - IMPORTANCE: Alopecia areata is an idiopathic cause of hair loss with limited therapeutic repertoire. OBJECTIVE: To compare the efficacy and safety of a high- vs low-potency topical corticosteroid in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized, blind, 2-arm, parallel-group, superiority trial was carried out over a 24-week period at a tertiary referral academic dermatology clinic at The Hospital for Sick Children in Toronto, Ontario, Canada. Forty-two children attending the outpatients clinic, 2 to 16 years of age with alopecia areata affecting at least 10% of scalp surface area, were eligible; 1 declined to participate. There were no withdrawals from the study. INTERVENTIONS FOR CLINICAL TRIALS: Patients were randomly assigned to receive clobetasol propionate, 0.05% cream, or hydrocortisone, 1%, cream. Patients applied a thin layer of the assigned cream twice daily to the areas of hair loss for 2 cycles of 6 weeks on, 6 weeks off, for a total of 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in scalp surface area with hair loss over 24 weeks following enrollment. RESULTS All participants were assessed at 6, 12, 18, and 24 weeks (except 1 participant who missed the 6-week visit). After adjusting for baseline hair loss, the clobetasol group had a statistically significant (P < .001) greater decrease in the surface area with hair loss, compared with the hydrocortisone group at all time points except at 6 weeks. One patient with extensive alopecia areata experienced skin atrophy that resolved spontaneously in 6 weeks. There was no difference observed in the number of patients with abnormal urinary cortisol at the beginning and the end of the study. CONCLUSIONS AND RELEVANCE: Topical clobetasol propionate, 0.05%, cream is efficacious and safe as a first-line agent for limited patchy childhood alopecia areata. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01453686. PMID- 24226569 TI - Structural variation around prolactin gene linked to quantitative traits in an elite Holstein sire family. AB - Digestion of genomic DNA with the restriction endonuclease Avail disclosed a probable insertion deletion of approximately 200 base pairs (bp) near the prolactin gene. Two alleles were apparent as three distinct hybridization patterns. These alleles were statistically associated with quantitative trait loci among sons of one elite Holstein sire family. The favorable genotype was correlated with the presence of a 1.15-kb hybridization band inherited from the sire when genomic DNA was probed with a full-length cDNA for prolactin. Pedigree estimates of genetic merit among genotypes were similar, differing by only 19.3 kg for milk in ancestor merit. Comparisons of genetic estimates for quantitative yield traits in offspring of this heterozygous sire showed significant (P<0.05) differences between homozygous genotypes for predicted difference milk (PDM), predicted difference dollars (PD$), cheese yield dollars, and protein dollars. The estimated differences between homozygous genotypes for USDA Transmitting Abilities of PDM, PD$, Cheese Yield $ and Protein $ were 282.93 kg, $74.35, $48.58 and $53.67, respectively. However, the estimated breeding values from progeny ranged over 900 kg in transmitting ability for milk. Frequency of the favorable marker allele was estimated to be 0.231 in the elite cow population used as dams of sons. These results demonstrate the potential of molecular biological techniques to discriminate between individuals within a family and to predict breeding values for selection schemes. PMID- 24226570 TI - Mapping quantitative trait loci using molecular marker linkage maps. AB - High-density restriction fragment length polymorphism (RFLP) and allozyme linkage maps have been developed in several plant species. These maps make it technically feasible to map quantitative trait loci (QTL) using methods based on flanking marker genetic models. In this paper, we describe flanking marker models for doubled haploid (DH), recombinant inbred (RI), backcross (BC), F1 testcross (F1TC), DH testcross (DHTC), recombinant inbred testcross (RITC), F2, and F3 progeny. These models are functions of the means of quantitative trait locus genotypes and recombination frequencies between marker and quantitative trait loci. In addition to the genetic models, we describe maximum likelihood methods for estimating these parameters using linear, nonlinear, and univariate or multivariate normal distribution mixture models. We defined recombination frequency estimators for backcross and F2 progeny group genetic models using the parameters of linear models. In addition, we found a genetically unbiased estimator of the QTL heterozygote mean using a linear function of marker means. In nonlinear models, recombination frequencies are estimated less efficiently than the means of quantitative trait locus genotypes. Recombination frequency estimation efficiency decreases as the distance between markers decreases, because the number of progeny in recombinant marker classes decreases. Mean estimation efficiency is nearly equal for these methods. PMID- 24226572 TI - Interspecific variation for thermal dependence of glutathione reductase in sainfoin. AB - Understanding the biochemical and physiological consequences of species variation would expedite improvement in agronomically useful genotypes of sainfoin (Onobrychis spp.) Information on variation among sainfoin species is lacking on thermal dependence of glutathione reductase (B.C. 1.6.4.2.), which plays an important role in the protection of plants from both high and low temperature stresses by preventing harmful oxidation of enzymes and membranes. Our objective was to investigate the interspecific variation for thermal dependency of glutathione reductase in sainfoin. Large variation among species was found for: (i) the minimum apparent Km (0.4-2.5 MUM NADPH), (ii) the temperature at which the minimum apparent Km was observed (15 degrees -5 degrees C), and (iii) the thermal kinetic windows (2 degrees -30 degrees C width) over a 15 degrees -45 degrees C temperature gradient. In general, tetraploid species had narrower (<=17 degrees C) thermal kinetic windows than did diploid species (~30 degrees C), with one exception among the diploids. Within the tetraploid species, the cultivars of O. viciifolia had a broader thermal kinetic window (>=7 degrees C) than the plant introduction (PI 212241, >2 degrees C) itself. PMID- 24226571 TI - Study of two different recombination events in maize cmsT-regenerated plants during reversion to fertility. AB - The change of phenotype from sterility to fertility for some cmsT callus tissue culture regenerated plants and their progenies has been correlated with changes in their mitochondrial genome. Those changes that have been analyzed here are the result of recombination events. Two different sets of repeated sequences have been found to be involved in those recombination events. The most common one is a recombination through a 127-bp repeat between various independently isolated revertants. The second one is a recombination through a 58-bp repeat. In every case the products of recombination containing the urf13 gene have been deleted. PMID- 24226573 TI - Long-term storage of Pennisetum glaucum (L.) R. Br. pollen. AB - Pearl millet [Pennisetum glaucum (L.) R. Br.] pollen has been successfully stored for 2,615 and 2,911 days at -18 degrees and -73 degrees C, respectively, and continues to be viable. Viability of pollen stored at -73 degrees C appears to be little affected either by pollen storage moisture contents below 7.2% or by storage in glass vial or zip-lock plastic bag containers. Pollen moisture content appears to be more critical for maintaining viability at -18 degrees C than at 73 degrees C. Glass vials appear to be more desirable for longer term (>3 years) storage at -18 degrees C. PMID- 24226574 TI - Identification of callus types for long-term maintenance and regeneration from commercial cultivars of wheat (Triticum aestivum L.). AB - Immature embryos, inflorescences, and anthers of eight commercial cultivars of Triticum aestivum (wheat) formed embryogenic callus on a variety of media. Immature embryos (1.0-1.5 mm long) were found to be most suitable for embryogenic callus formation while anthers responded poorly; inflorescences gave intermediate values. Immature embryos of various cultivars showed significant differences in callus formation in response to 11 of the 12 media tested. No significant differences were observed when the embryos were cultred under similar conditions on MS medium with twice the concentration of inorganic salts, supplemented with 2,4-D, casein hydrolysate and glutamine. Furthermore, with inflorescences also no significant differences were observed. Explants on callus formation media formed two types of embryogenic calli: an off-white, compact, and nodular callus and a white compact callus. Upon successive subcultures (approximately 5 months), the nodular embryogenic callus became more prominent and was identified as 'aged callus'. The aged callus upon further subculture, formed an off-white, soft, and friable embryogenic callus. Both the aged and friable calli maintained their embryogenic capacity over many subculture passages (to date up to 19 months). All embryogenic calli (1 month old) from the different callus-forming media, irrespective of expiant source, formed only green shoots on regeneration media that developed to maturity in the greenhouse. There were no significant differences in the response of calli derived from embryos and inflorescences cultured on the different initiation media. Also, the shoot-forming capacity of the cultivars was not significantly different. Anther-derived calli formed the least shoots. Aged and friable calli on regeneration media also formed green shoots but at lower frequencies. Plants from long-term culture have also been grown to maturity in soil. PMID- 24226575 TI - Theory and application of open-pollination and polycross in forage grass breeding. AB - Progeny testing and selection of forage grasses by means of growing half-sib (HS) families from openpollination and polycross have been considered from theoretical and practical points of view. Special attention has been paid to the genetic variation within half-sib families, which is expected to be large as compared to the genetic variation between families. Based on observations of individual plants within plots, the environmental component of the variation is expected to be large and nonestimatable. The results of an experiment in meadow fescue (Festuca pratensis Huds.) are presented. In this experiment, randomly selected individual plants within HS families were cloned and laid out in randomized blocks. For the characters observed (earliness and raw matter yield) no significant variance component for dominance was found. The highly significant additive component estimated for earliness, as well as for yield, after each of three cuts and in total were about three times as large within as between families, as expected from the theoretical considerations. The estimated response to selection was much higher for a combination of between- and within-family selection as compared to free clone or family mean selection alone. It is suggested that a program for progeny testing and selection in a base population of perennial forage grasses should start with an experiment in which a large number of randomly selected parental clones and a fixed number of clones from each of the half-sib families derived from the mother genotypes are grown simultaneously. The selected clones within superior families could later on be further cloned, placed in a polycross field, and the new HS-families could be sown in ordinary field trials at various locations for further selection. PMID- 24226576 TI - Bialaphos selection of stable transformants from maize cell culture. AB - Stable transformed Black Mexican Sweet (BMS) maize callus was recovered from suspension culture cells bombarded with plasmid DNA that conferred resistance to the herbicide bialaphos. Suspension culture cells were bombarded with a mixture of two plasmids. One plasmid contained a selectable marker gene, bar, which encoded phosphinothricin acetyl transferase (PAT), and the other plasmid encoded a screenable marker for beta-glucuronidase (GUS). Bombarded cells were selected on medium containing the herbicide bialaphos, which is cleaved in plant cells to yield phosphinothricin (PPT), an inhibitor of glutamine synthetase. The bialaphos resistant callus contained the bar gene and expressed PAT as assayed by PPT inactivation. Transformants that expressed high levels of PAT grew more rapidly on increasing concentrations of bialaphos than transformants expressing low levels of PAT. Fifty percent of the bialaphos-resistant transformants tested (8 of 16) expressed the nonselected gene encoding GUS. PMID- 24226577 TI - Protoplast-fusion-derived Solanum cybrids: application and phylogenetic limitations. AB - We established interspecific Solanum cybrids in order to study the intrageneric nuclear-organelle compatibility and the introgression of advantageous plasmone coded breeding traits into potato. Cybridization was performed by the donor recipient protoplast-fusion procedure. We found that the plastomes of S. chacoense, S. brevidens, and S. etuberosum could be transferred into the cybrids having S. tuberosum nuclear genomes; chondriome components were likewise transferred from the former species into these cybrids. The combination with S. chacoense as organelle donor and potato as recipient resulted in green fertile plants with potato morphology. By using S. etuberosum as an organelle donor and potato as recipient, male-sterile cybrid plants, most of them having pigmentation abnormalities, were obtained. The combination of S. brevidens with potato resulted in palegreen (almost albino) regenerants. The latter albino plantlets had both the chloroplast DNA and the mitochondrial DNA of the donor (S. brevidens) and did not survive the transfer into the greenhouse. An immediately applicative result of this study is the de novo establishment of male-sterile plants in a potato cultivar. Such plants should be useful as seed parents in the production of hybrid, true-potato seeds. PMID- 24226578 TI - Genetic analysis of resistances to races 1 and 2 of Fusarium oxysporum f. sp. lycopersici from the wild tomato Lycopersicon pennellii. AB - Resistance to race 3 of Fusarium wilt in the wild tomato Lycopersicon pennellii (LA 716) was previously found to be controlled by one major locus, I-3, tightly linked to Got-2 on chromosome 7. This accession was also found to carry resistance to races 1 and 2; a genetic analysis of these resistances is reported in this paper. This analysis proceeded in two steps. First, allelism tests demonstrated that race 1 and 2 resistances carried by L. pennellii were not allelic to the I and I-2 genes originally incorporated into L. esculentum from L. pimpinellifolium. Second, an interspecific backcross with L. pennellii (BC1) was used to determine the mode of inheritance of these new resistances and their chromosomal location by segregation and linkage analysis. BC1 responses to each of the races were determined using progeny tests (BC1S1). BC1S1 plants were inoculated with race 1 or 2 and evaluated after 1 month using a visual disease rating system; mean disease ratings were calculated for each BC1 individual for each race based on the progeny scores. A bimodal frequency distribution of the BC1 mean disease ratings was observed for both races, indicating that one major locus controlled resistance in each case. Statistical comparisons of the mean disease ratings of homozygous versus heterozygous individuals at each of 17 segregating enzyme loci were used to map the resistances to races 1 and 2. Tight linkage was detected between the enzyme locus Got-2 and resistances to both races, as was previously reported for the I-3 locus. Therefore, the Got-2 locus can be used as a selectable marker for resistances to all three races. The relationship of these resistances is discussed in the paper. In addition, as previously reported for race 3, significance was also detected for the chromosome segment marked by Aps-2 on chromosome 8 for both races. Currently many cultivars carry I and I-2 resistances to races 1 and 2. Incorporation of the LA 716 resistances to these two races into cultivars may reduce the likelihood of new race development. PMID- 24226579 TI - Biochemical characterization of lines descended from 8x triticale x 4x triticale cross. AB - Fifty-two progenies originating from a cross between 8x and 4x triticale were submitted to cytogenetic analyses and to various electrophoretic studies [high molecular-weight (HMW) glutelins, HMW secalins, gamma-secalins, alpha and omega gliadins, beta-amylases] to identify new genetic structures, more specifically the input of the D genome in a genetic context other than the wheat one. Markers of the rye genome (HMW and omega-secalins) were identified in all of the triticale lines, but they originated either from the 4x or from the 8x parent, or from both. Chromosomes 4A, 1B, and 2R, present in both parents, showed the same banding patterns in all progenies. Chromosomes 1R and 5R, present in both parents, showed heterogeneous labelling. The expression of chromosomes 6A, 1D, and 4D, present in the 8x parent only, was more complex with a possible involvement of a regulatory system. Several hexaploid progenies had introgressed part of the D genome, suggesting that crossing 8x and 4x triticale was a practicable approach for transferring D chromosomes into hexaploid triticale. PMID- 24226580 TI - Within-population variation in susceptibility to Agrobacterium tumefaciens A281 in Picea abies (L.) Karst. AB - The purpose of this study was to investigate the genetic variation of susceptibility to Agrobacterium within a Picea abies population. Tumor formation was studied in 16 open-pollinated families belonging to a central Swedish population of Picea abies. Strain A281 of Agrobacterium tumefaciens was used to infect 3-monthold seedlings in a five-block greenhouse experiment. The analysis of variance showed strong significance for the between-family variation of tumor formation percentages, varying from 28% to 73%. The most susceptible material will be suitable for experiments on the production of transgenic plants in vitro using disarmed Agrobacterium strains. PMID- 24226581 TI - A genetic analysis of mutations recovered from tomato following Agrobacterium mediated transformation with the maize transposahle elements Activator and Dissociation. AB - The maize autonomous transposable element, Activator (Ac), and the nonautonomous element Dissociation (Ds), were introduced into the tomato cultivars VF36 and VFNT Cherry by Agrobacterium-mediated transformation. Progeny families from 145 primary transformants were scored at the seedling stage for phenotypically variant individuals. When VF36 was transformed, 20% of families had progeny with aberrant phenotypes. The mutation frequency in VFNT Cherry transformants was lower; in this cultivar 7% of the transformants had progeny segregating for seedling mutations. The majority of the mutations showed monogenic inheritance in the R1 population, suggesting that the mutations occurred early in the transformation/regeneration process. One mutation, however, was recovered at low frequency in the R1, suggesting a late mutagenesis event. When tomato was transformed with either the Ac or Ds elements, no differences in mutation frequencies were observed. Since Ac is transpositionally active in tomato transformants while Ds is not, these numbers indicate that the mutation frequency inherent to the transformation process is higher than the mutational activity of Ac. These results demonstrate that efficient gene tagging using heterologous transposable elements will require screening for transposon-induced mutations in later generations. PMID- 24226582 TI - Analysis of DNA from a Beta procumbens chromosome fragment in sugar beet carrying a gene for nematode resistance. AB - We have begun to apply techniques for the preparation and anaylsis of large DNA segments from sugar beet (Beta vulgaris) addition lines carrying a mitotically stable chromosome fragment from B. procumbens that confers monogenic resistance to the nematode Heterodera schachtii, with a view towards isolating the resistance gene. DNA probes specific for this chromosome fragment were selected, and various methods for cloning genome-specific fragments, including probes from megabase DNA separated in pulsed-field slab gels, are compared. Probes that display high homology to B. procumbens have been used for hybridization of a representative genomic library and for initial step in mapping the chromosome fragment via pulsed-field gel electrophoresis after restriction with infrequently cutting enzymes. Our data indicate that DNA molecules from the entire chomosome fragment can be separated from protoplast DNA lysates. PMID- 24226583 TI - Genetic variability of leaf esterases in Triticum aestivum L. 2n=6x=42. AB - Starch gel electrophoresis with two different buffer systems and several substrates and inhibitors have been used to study the electrophoretic variability of esterases in leaves of cultivars of Triticum aestivum. Each one of the buffer systems showed different levels of variability, according to the electrophoretic patterns. At the same time green and etiolated leaves showed different patterns in each buffer system. The variability was dependent upon the developmental stage of the leaves. According to the results from chromosomal location, the genes controlling esterases in green leaves were located in homoeology group 3, while the genes controlling esterases in etiolated leaves were in homoeology group 6. But both esterase isozymes showed a similar electrophoretic migration and a similar reponse to substrates and inhibitors. The possible origin of both sets of genes due to an interchromosomal duplication is discussed. PMID- 24226584 TI - Effect of various irradiation treatments of plant protoplasts on the transformation rates after direct gene transfer. AB - In P. hybrida and B. nigra an enhancement of transformation rates (direct gene transfer) of about six to seven-fold was obtained after irradiation of protoplasts with 12.5 Gy (X-ray). The effect of protoplast irradiation was similar in experiments where protoplasts were irradiated 1h before transformation (X-ray/DNA) or 1h after completion of the transformation procedure (DNA/X-ray). Increased X-ray doses up to 62.5 Gy resulted in further enhancement of percentages of transformed colonies, indicating a correlation between relative transformation frequencies (RTF) and the doses applied. Estimation of degradation rates of plasmid sequences in plant protoplasts yielded a reduction of plasmid concentration to 50% 8-12 h after transformation. In 1-day-old protoplasts, the level of plasmid fragments dropped to 0%-10% compared to 1h after transformation. The results demonstrate that the integration rates of plasmid sequences into the plant genome may in part be governed by DNA repair mechanisms. This could be an explanation for the observed genotypic dependence of transformation rates in different plant species and plant genotypes. Gene copy number reconstructions revealed enhanced integration rates of plasmid sequences in transformed colonies derived from irradiated protoplasts. PMID- 24226585 TI - Chromosomal identification and meiotic behavior of reciprocal translocations in a rye polymorphic population. Evolutionary implications. AB - The spontaneous interchange polymorphism of rye cultivar "Ailes" is composed, as can be deduced from the chromosomal identification of the interchanges analyzed, of several different reciprocal translocations in which the chromosomes of its haploid complement are involved with a similar frequency, except for chromosomes 4R and 6R. Several features of chromosome behavior at metaphase I, such as configuration and orientation of quadrivalents and frequency of chiasmata, were analyzed in structural heterozygotes for different interchanges. The two main factors affecting the orientation of quadrivalents at metaphase I proved to be the morphology of these chromosome associations at metaphase I and, in particular, the frequency of bound chromosome arms that they showed. A genotypic control of alternate orientation of quadrivalents independent of chiasmata frequency was not detected. In addition, the frequency of alternate orientation shows no relation to the fitness. Possible evolutionary implications of the results obtained are discussed. PMID- 24226586 TI - Genetic differences between the Chinese and European races of the common carp : 6. Growth of fish in cages. AB - Relative growth rates of six genetic groups of common carp were compared in small netting cages and in earthen ponds. These groups of carp included an isolate of the Chinese 'Big Belly Carp', its crossbred with a European isolate, and four European progenies, purebreds or crossbreds. Five different environments were produced in the ponds, mainly by varying the stocking rates of carp. Each of the (ten) cages was treated as a different environment. Each cage and each pond were stocked with random samples of each genotype, i.e., 'communal testing' was carried out. The performance of a given genotype in a given environment was estimated from its weight gain in that environment. The mean weight gain of all groups, stocked into a given environment, was taken as an estimate of that environment as it influenced the growth of carp. The characteristics of the regression of growth of a given genotype on the environment in which it grew [i.e., the coefficient of regression (b) and the Y intercept (a)] are taken as measures of its adaptation to that environment. No real differences in adaptation to pond versus cage conditions were isolated for four of the tested groups, the Chinese x European crossbred, the two European crossbreds and one of the European purebreds. The Chinese carp showed a specific adaptation to growth in ponds (or a lack of adaptation to growth in cages), whereas Dor-70 was specifically adapted to cage conditions. These results may be explained by the genetic history of the two lines. The Big Belly Carp was domesticated under conditions of Chinese subsistence aquaculture, which apparently generated an adaptation to gathering and utilizing natural foods. These are prominently absent in cages. Dor-70 was produced in a long-term selection experiment, which apparently generated a response for growth in cages. These results may be of applicative value, if common carp were to be considered as candidates for commercial cage aquaculture. It would then be important to use strains like Dor-70, which are adapted to these conditions, and avoid strains like the Chinese Big Belly carp. PMID- 24226587 TI - Estimation of heritability and genetic trend in populations at a physiological limit. AB - Limits on physiological processes, though perhaps unknown, must exist. The reported simulations evaluate the effect of a physiological limit on the estimation of genetic parameters and genetic progress. Simulation experiments reveal no change in the estimate of heritability, even for limits as restrictive as 1.5 phenotypic standard deviations above the population mean. However, estimates of additive genetic and environmental variance shrink as limits on performance increase in severity. Simulated physiological limits do not affect the rate of genetic progress. However, absolute measures of estimated genetic change are less than those predicted by response equations. PMID- 24226588 TI - Genetic analysis of the obligate parasitic barley powdery mildew fungus based on RFLP and virulence loci. AB - Genome organization of the biotrophic barley powdery mildew fungus was studied using restriction fragment length polymorphism (RFLP). Genomic DNA clones containing either low-or multiple-copy sequences appeared to be the best RFLP markers, as they frequently revealed polymorphisms that could be readily detected. A total of 31 loci were identified using 11 genomic DNA clones as probes. Linkage analysis of the 31 RFLP loci and five virulence loci resulted in the construction of seven groups of linked loci. Two of these contained both RFLP markers and virulence genes. RFLP markers were found to be very efficient in characterizing mildew isolates, as only three markers were necessary to differentiate 28 isolates. The DNA of the barley powdery mildew fungus appeared to contain a considerable number of repetitive sequences dispersed throughout the genome. PMID- 24226590 TI - Erratum. PMID- 24226589 TI - Autofertility and rate of cross-fertilization: crucial characters for breeding synthetic varieties in faba beans (Vicia faba L.). AB - To increase the level and stability of yield in faba beans (Vicia faba L.), heterosis must be exploited. Hybrids are not available because of the instability of male sterility. Synthetic varieties can and should be bred. Thus, we studied the reproductive behavior of this partially allogamous, insect-pollinated crop. Autofertility (AF) and the rate of cross-fertilization (C) were measured in 36 inbred lines and 28 crosses in F1, F2, and F3 generations for 3 years at Hohenheim, Stuttgart, FRG. Heterozygosity strongly increased AF and decreased C. AF was negatively correlated with C. AF varied from 1% to 98%, and C varied from 7% to 82%. Heritability for both characters was high. For an optimum exploitation of heterosis, breeders should utilize lines with high C as variety components. It is often labor-intensive to multiply such lines, due to low AF. Hence, breeders tend to use autofertile lines with rather limited C. We showed that even in this case about 50% of the total heterosis, which equals a yield increase of at least 25% over the inbred line level, is realized. An increase in yield stability due to heterogeneity will occur simultaneously. PMID- 24226591 TI - Division and gametophytic tissue formation from protoplasts of young sporophytes in fern Lygodium japonicum. AB - Protoplasts isolated enzymatically from juvenile leaflets of sporophytes in fern Lyqodium japonicum were inoculated in a MS medium containing NAA 2.7 MUm, BAP 2.2 MUm, 0.6 M mannitol, and 0.05 M sucrose. Cell division took place within 8 days of culture initiation, and after 30 days cell-clusters with 10-15 cells were observed. When the cell-clusters were transferred into fresh hormone-free medium containing no mannitol, they developed rhizoids and protonema-like regenerants. About 2 months later, cordate prothallia developed bearing both antheridia and archegonia. PMID- 24226592 TI - Controlled cell wall regeneration for efficient microinjections of Nicotiana tabacum var. Carlson protoplasts. AB - Nicotiana tabacum var. Carlson protoplast culture conditions were modified to contain a cell wall inhibitor, 2,6-dichlorobenzonitrile, in order to delay cell wall regeneration and to allow efficient nuclear and cytoplasmic microinjections. Under modified conditions, the protoplast preparations appeared healthier as compared to the control protoplasts and showed no resistance at all during microinjection. Furthermore, the duration of protoplast microinjection was extended for up to 3-4 days. In order to set up nuclear microinjections, the nuclei of these protoplasts were stained either before or after immobilization without any adverse effect on their mitotic activity. Successful cytoplasmic microinjections were demonstrated by injecting Alfalfa mosaic virus (AMV) RNA, which resulted in viral infection of 14% of the injected protoplasts. PMID- 24226593 TI - Genetic transformation of foxglove (Digitalis purpurea) by chimeric foreign genes and production of cardioactive glycosides. AB - The chimeric neo and gus genes on a mini Ti vector are efficiently transferred into the genome of fox glove (Digitalis purpurea L.) using a binary vector system based on a rootinducing Ri plasmid, pRi15834. The transgenic state of established transformed roots was confirmed by Southern blot analysis and by detection of agropine and mannopine. The expression of the chimeric genes controlled by the promoters from TR 1'-2' genes, nos gene and cauliflower mosaic virus 35S RNA was demonstrated by enzymatic and histochemical assays of neomycin phosphotransferase II and beta-glucuronidase. Enzyme-linked immunosorbent assay (ELISA) was carried out using polyclonal antibody reactable against digitoxin to investigate the production of cardenolides. The results of ELISA indicated that the cardioactive glycosides were highly produced in the green transformed hairy roots. PMID- 24226594 TI - Long term culture and caffeine production of immobilized coffee (Coffea arabica) L. cells in polyurethane foam. AB - Coffee (Coffea arabica L.) cells could be immobilized in polyurethane foam and subcultured repeatedly for a long time. Four phases were observed for cell growth and caffeine production, I; immobilization, II; growth, III; caffeine production, IV; regrowth. Their periods were influenced by the number of foam particles. Especially in the phase III, the immobilized cells produced a relatively large amount of caffeine in the subculture numbers 5-8 (34 cubes) when the fresh weight of the immobilized cells decreased despite culture in growth medium (DK medium). Caffeine production appeared to have a negative correlation with the growth of the immobilized cells throughout the subcultures. PMID- 24226595 TI - Direct analysis of RNA transcripts in electroporated carrot protoplasts. AB - We describe a method for direct analysis of RNA transcribed from DNA introduced into carrot cells by electroporation. Octopine synthase RNA transcribed from the plasmid p35SOcs was detected in total and poly A(+) RNA on Northern blots and in RNA protection assays. The highest level of octopine synthase transcript was detected at approximately 8 hrs post-electroporation, although RNA could still be detected after 48 hrs. This method allows detection of foreign gene expression in a plant system and bypasses the need for reporter genes. PMID- 24226596 TI - Specific differences in tolerance to exogenous berberine among plant cell cultures. AB - The tolerance of plant cells to exogenously administered berberine, an antimicrobial isoquinoline alkaloid, was studied using berberine-producing and nonproducing cell suspension cultures. Both Coptis japonica and Thalictrum flavum cells, which have an intrinsic ability to synthesize berberine, took up exogenous berberine from the culture medium by an energy-requiring active transport to accumulate it exclusively in vacuoles. By contrast, T. minus cells, which excrete indigenous berberine mostly into the medium, did not take up exogenously supplied berberine, indicating that the alkaloid transport in this species is unidirectional. No inhibition of cell growth by exogenous berberine was observed in the three berberine-producing cell cultures. On the other hand, a small amount of exogenous berberine strongly inhibited cell growth in the berberine-free cultures of Datura innoxia, Catharanthus roseus, and Paeonia albiflora. The berberine taken up actively by Datura cells could not be transported into vacuoles but was dispersed in the cytoplasm, causing a severe inhibition of cell growth. PMID- 24226597 TI - Somatic embryogenesis and plant regeneration from callus cultures of Bunium persicum Boiss. AB - Callus was obtained from mericarps of Bunium persicum Boiss. on MS medium supplemented with 2.0 mg/1 2,4-D and 4.0 mg/1 Kn. Small white clumps of compactly packed cells developed on the callus on a medium containing 1.0 mg/1 2,4-D and 0 mg/1 Kn. These cell clumps differentiated numerous globular embryos on the same medium. Embryo maturation and germination was achieved on the basal as well as on 1 mg/1 Kn supplemented medium. All regenerated plants examined were normal diploids with 2n=14. PMID- 24226598 TI - Callus formation from root protoplasts of Quercus rubra L. (red oak). AB - Root protoplasts of Quercus rubra L. were isolated from 12 day old seedlings with an enzyme mixture containing Cellulase R1O + Rhozyme HP150 + Macerozyme R1O, supplemented with cysteine and bovine serum albumin.Protoplasts were purified by a Ficoll density gradient centrifugation and cultured at low density in a liquid medium. The modified woody plant medium, containing 2.2 MUM benzyladenine + 1.8; MUM zeatin + 5.3 MUM alpha-naphthaleneacetic acid + 2.2 MUM dichlorophenoxyacetic acid, allowed sustained divisions and formation of microcalluses.Protoplast - derived microcallus developed into green and compact callus when transferred to an agarose solidified medium, supplemented with casein hydrolysate and indole 3 acetic acid (devoid of 2,4 dichlorophenoxyacetic acid) and placed under low illumination. PMID- 24226599 TI - Accumulation of anthocyanins enhanced by a high osmotic potential in grape (Vitis vinifera L.) cell suspensions. AB - A cell suspension of grape, Vitis vinifera L. cv Gamay Freaux, was grown under different conditions of water stress (high external osmotic potential) induced by an increase of sucrose concentration or by the addition of mannitol to the culture medium. Best growth (cell density) was achieved in the low osmotic potential medium. Increasing the osmotic potential of the medium from -0.5 MPa to -0.9 MPa medium resulted in a significant increase in accumulation of anthocyanins in pigmented cells. Regulation of the osmotic potential of culture medium may be useful in controlling anthocyanin production. PMID- 24226600 TI - Extracellular accumulation of high specific-activity peroxidase by cell suspension cultures of cowpea. AB - Cell suspension cultures of cowpea (Vigna sp.) were able to produce extracellular peroxidase. Different growth regulator concentrations induced different peroxidase activity in callus. The crude extracellular medium after four weeks of culture showed higher (6 times) specific peroxidase activity and higher thermo stability than commercial horse-radish peroxidase. The commercial production of peroxidase enzyme from cowpea by utilizing plant cell cultures is discussed. PMID- 24226601 TI - Growth characteristics and ion contents of non-selected and salt-selected callus lines of highbush blueberry (Vacdnium corymbosum) cultivars Blue Crop and Denise Blue. AB - Non-selected and sodium chloride selected callus lines of Vacdnium corymbosum L.cv Blue Crop and cv. Denise Blue were grown on media supplemented with 0-100 mM NaCl. For both cultivars, fresh weight and dry weight yields were greater in selected lines on all levels of NaCl. Selected lines of Blue Crop displayed better growth than selected lines of Denise Blue at most concentrations of NaCl. Internal Na(+) and Cl(-) concentrations in selected and non-selected lines of both cultivars increased as external concentration was raised. However, selected lines of Blue Crop and Denise Blue accumulated more Na(+) and Cl(-) than non selected lines. Selected lines of both cultivars maintained higher levels of K(+) than non-selected lines on all external NaCl levels. Selected lines of Blue Crop had higher levels of Na(+) and Cl(-) than that of Denise Blue. The results suggest Na(+) and Cl(-) accumulation could be a mechanism allowing better growth in selected lines at moderate salinity levels (50-75 mM NaCl). PMID- 24226602 TI - Effect of NaCl on lipid content of plasma membranes isolated from roots and cell suspension cultures of the dicot halophyte Kosteletzkya virginica (L.) Presl. AB - Lipid concent was examined in plasma membrane fractions isolated by discontinuous sucrose density-gradient centrifugation from both salinized and unsalinized roots and cell suspension cultures of Kosteletzkva virginica (L.) Presl., seashore mallow, a halophytic dicot. The distribution of marker enzymes along the gradient indicated that plasma membranes of roots and cell cultures accumulated primarily at the 34%/45% interface. Total sterol and phospholipid content increased significantly in plants and cell suspensions grown on salinized nutrient media. In addition, K. virginica plasma membranes were constitutively rich in sterols, and a high sterol-to-phospholipid ratio was maintained or elevated under saline conditions. These results are discussed in relation to membrane composition as a mechanism involved in the cellularly based salt tolerance of K. virginica. PMID- 24226603 TI - Agrobacterium tumefaciens mediated transformation and regeneration of muskmelon plants. AB - Transgenic muskmelon (Cucumis melo L.) plants were produced efficiently by inoculating cotyledon explants with Agrobacterium tumefaciens strain LBA4404 bearing a Ti plasmid with the NPT II gene for kanaymcin resistance. After co cultivation for three days, expiants were transferred to melon regeneration medium with kanamycin to select for transformed tissue. Shoot regeneration occurred within 3-5 weeks; excised shoots were rooted on medium containing kanamycin before transferring to soil. Morphologically normal plants were produced in three months. Southern blot analysis confirmed that ca. 85% of the regenerated plants contained the NPT gene. Dot blot analysis and leaf callus assay of progeny of transgenic plants verified transmission of the introduced gene(s) to the next generation. Factors affecting transformation efficiency are discussed. PMID- 24226604 TI - Axillary shoot proliferation and growth of Populus deltoides shoot cultures. AB - Shoot cultures of four genotypes of Populus deltoides Bartr. ex Marsh. were established from adventitious shoots regenerated from internodal stem explants. Stable shoot cultures for all four genotypes were maintained in a continuous culture regime for over one year. The stable shoot cultures were used as explants to investigate the effects of zeatin concentration and genotype on axillary shoot production and growth. The concentration of zeatin significantly affected the production of axillary shoots, with 1.0 mgL(-1) zeatin producing the greatest number of shoots (31.0 shoots per culture vessel) while 0.25 mgL(-1) zeatin produced the greatest growth (5.9 mg per axillary shoot) when measured by dry weight accumulation per shoot. Genotypic differences were significant in the production and growth of axillary shoots. PMID- 24226605 TI - Co-transformation of indica rice protoplasts with gusA and neo genes. AB - Protoplasts of the indica rice (Oryza sativa L.) variety, IR54, were transiently transformed with the gusA gene and stably transformed with both the neo and gusA genes. We show that PEG-mediated co-transformation of protoplasts with two genes on separate plasmids coupled with selection on kanamycin is an effective way of transferring foreign gene(s) into the indica rice genome. The efficiency of co transformation was generally 20-30%, i.e. the frequency of kanamycin-resistant calli having both the neo and gusA active genes. Southern blot analysis using a probe for gusA indicated integration of several copies of the gene, often as head to tail tandem repeats. PMID- 24226606 TI - Comments on fluorescence methods for probing local deviations from lamellar packing. AB - Fluorescence probes have been used to monitor the conversion from the lamellar to nonlamellar phases. In addition there is current interest in understanding the nature of the changes in the physical properties of phospholipid bilayers that are correlated with their propensity for forming nonlamellar phases. Fluorescent probes have been used to demonstrate changes in surface hydrophobicity, quenching efficiency, and rates of interbilayer transfer of fluorescently labeled analogs. These studies are beginning to provide an assessment of the nature of the differences between stable bilayers and those that readily convert into inverted phases. Such studies are important because these differences in physical properties often lead to altered membrane functional behavior. PMID- 24226607 TI - Long-lived fluorescence probes for studying lipid dynamics: A review. AB - A great many studies have focused on the heterogeneous packing of lipids in the bilayer matrix. However, less attention has been directed toward the temporal aspects of these lipid-lipid interactions. Studies of lipid packing fluctuations, or 'gel-fluid' exchange, using fluorescence probe methodologies have been limited. This limitation arises from thesubmicrosecond time scale over which the fluctuations are expected to occur. Traditionally, dynamic studies of lipid bilayers have been restricted to the nanosecond time regime, and the submicrosecond time 'window' has not been explored in any great depth by fluorescence methods, although persistent lipid dynamics has been evident. Probes with long fluorescence lifetimes (several hundred nanoseconds) have the potential to expand this important time 'window,' providing information on 'gel-fluid' exchange rates and insights into how important biological effectors such as proteins, cholesterol, and anesthetics affect or modulate these fluctuations. Using the long-lived fluorescence probe coronene, combined with time-resolved fluorescence methods geared toward microheterogeneity, we present a view of bilayer dynamics in an alternate time domain. Fluorescence probes are expected to inhabit an equilibrium between fluid and gel environments. Some probes remain in their respective environments throughout their excited-state lifetime, while others reside in surroundings that will change (i.e., 'melt'). Long-lived fluorescence membrane probes can provide direct estimates of submicrosecond lipid fluctuation or 'melt' rates. Simple Landau modeling leads to adistribution of 'melt' rates and provides an attractive alternative to a simplercompartmental model where a unique lipid fluctuation of gel-fluid exchange rate is measured. Thedistribution model is probe independent (defined by thermodynamic quantities) and can be applied generally to the rotational motions of fluorescence probes embedded in the lipid bilayer. PMID- 24226608 TI - Fluorescence techniques for probing water penetration into lipid bilayers. AB - Fluorescence spectroscopy can be used as a highly sensitive and localized probe for hydration in lipid bilayers. Water associates with the head-group region, where it participates in an interlipid network of hydrogen bonds. Deeper in the bilayer, water is contained within acyl-chain packing defects. Fluorescence methodology is available to probe both the interstitial and head-group hydration in lipid bilayers, and results are in good agreement with other techniques. Using fluorescence spectroscopic approaches, cholesterol is shown to dehydrate the acyl chain region, while hydrating the head-group region. Membrane proteins appear to increase acyl-chain hydration at the protein-lipid interface. Overall fluorescence spectroscopic techniques may be most effective in studying the water content of lipid bilayers and especially of biological membranes. PMID- 24226609 TI - Fluorescence lifetimes of diphenylhexatriene-containing probes reflect local probe concentrations: Application to the measurement of membrane fusion. AB - An important process in the life of a cell is fusion between cellular membranes. This is the process by which two cellular compartments surrounded by different membranes join to become a single compartment surrounded by a single membrane, without significant loss of compartment contents. To demonstrate fusion, the cell biophysicist must demonstrate all three critical aspects of the process: (1) mixing of membrane components, (2) mixing of compartment contents; and (3) retention of compartment contents. Most commonly, accomplishing this involves the use of fluorescence probes. The general theme to the methods described involves some form of concentration-dependent quenching. An unique method developed in our laboratory utilizes the concentration dependence of the fluorescence lifetime of a phosphatidylcholine containing carboxyethyl diphenylhexatriene at position 2 and palmitic acid at position 1 of glycerol (DPHpPC). The fluorescence lifetime of this molecule and that of its parent fluorophore diphenylhexatriene (DPH) shorten dramatically as their two-dimensional concentrations in a membrane increase. This "lifetime quenching" can be described by dimer formation that reduces the symmetry of the DPH excited state. This phenomenon allows one to use the fluorescence lifetime to gain insight into the local concentration of probe in microscopic regions of a membrane. One application of this is in distinguishing lipid transfer between the outer leaflets of two contacting membrane bilayers from fusion between these membranes that leads to mixing of lipids in both the inner and outer leaflets of the membrane bilayers. This allows a single measurement to demonstrate fusion between membrane pairs. PMID- 24226610 TI - Determination of DPH order parameters in unoriented vesicles. AB - This article reviews the determination of orientational order parameters in non macroscopically oriented membranes from the data obtained with the fluorescent probe all-trans-1,6-diphenyl-1,3,5-hexatriene (DPH). Special attention is paid to the effect of microheterogeneity in the probe environment on the recovered values of the order parameters. An effort is made to accommodate new findings in the existing picture of orientational order in membranes. PMID- 24226611 TI - Fluorescence lifetime distributions in membrane systems. AB - Membranes are complex biological systems that display heterogeneity at all spatial scales. At a molecular level, the heterogeneity arises from lipid and protein composition. At the cellular level, heterogeneity is due to membrane organization and large scale morphology. A quantitative evaluation of membrane heterogeneity at a microscopic level is very important for several fields of membrane studies. We have developed a method for the analysis of the decay of fluorescent membrane probes that can provide a quantity sensitive to membrane heterogeneity. This method is based on the analysis of the fluorescence decay using continuous lifetime distributions. The major challenge in the interpretation of the analysis results is in the identification, at a molecular level, of the mechanisms that influence the fluorescence decay. In this review we illustrate the principles of data analysis and we show examples of identification of the measured parameters with specific variables that affect membrane heterogeneity. PMID- 24226612 TI - Membrane lipid domains and dynamics as detected by Laurdan fluorescence. AB - 2-Dimethylamino-6-lauroylnaphthalene (Laurdan) is a membrane probe of recent characterization, which shows high sensitivity to the polarity of its environment. Steady-state Laurdan excitation and emission spectra have different maxima and shape in the two phospholipid phases, due to differences in the polarity and in the amount of dipolar relaxation. In bilayers composed of a mixture of gel and liquid-crystalline phases, the properties of Laurdan excitation and emission spectra are intermediate between those obtained in the pure phases. These spectral properties are analyzed using the generalized polarization (GP). TheGP value can be used for the quantitation of each phase. The wavelength dependence of theGP value is used to ascertain the coexistence of different phase domains in the bilayer. Moreover, by following the evolution of Laurdan emission vs. time after excitation, the kinetics of phase fluctuation in phospholipid vesicles composed of coexisting gel and liquid-crystalline phases was determined.GP measurements performed in several cell lines did not give indications of coexistence of phase domains in their membranes. In natural membranes, Laurdan parameters indicate a homogeneously fluid environment, with restricted molecular motion in comparison with the phospholipid liquid crystalline phase. The influence of cholesterol on the phase properties of the two phospholipid phases is proposed to be the cause of the phase behavior observed in natural membranes. In bilayers composed of different phospholipids and various cholesterol concentrations, Laurdan response is very similar to that arising from cell membranes. In the absence of cholesterol, from the steady-state and time-resolved measurements of Laurdan in phospholipid vesicles, the condition for the occurrence of separate coexisting domains in the bilayer has been determined: the molecular ratio between the two phases must be in the range between 30% and 70%. Below and above this range, a single homogeneous phase is observed, with the properties of the more concentrated phase, slightly modified by the presence of the other. Moreover, in this concentration range, the calculated dimension of the domains is very small, between 20 and 50 A. PMID- 24226613 TI - Video fluorescence microscopic techniques to monitor local lipid and phospholipid molecular order and organization in cell membranes during hypoxic injury. AB - Digitized video microscopy is rapidly finding uses in a number of fields of biological investigation because it allows quantitative assessment of physiological functions in intact cells under a variety of conditions. In this review paper, we focus on the rationale for the development and use of quantitative digitized video fluorescence microscopic techniques to monitor the molecular order and organization of lipids and phospholipids in the plasma membrane of single living cells. These include (1) fluorescence polarization imaging microscopy, used to measure plasma membrane lipid order, (2) fluorescence resonance energy transfer (FRET) imaging microscopy, used to detect and monitor phospholipid domain formation, and (3) fluorescence quenching imaging microscopy, used to spatially map fluid and rigid lipid domains. We review both the theoretical as well as practical use of these different techniques and their limits and potential for future developments, and provide as an illustrative example their application in studies of plasma membrane lipid order and topography during hypoxic injury in rat hepatocytes. Each of these methods provides complementary information; in the case of hypoxic injury, they all indicated that hypoxic injury leads to a spatially and temporally heterogeneous alteration in lipid order, topography, and fluidity of the plasma membrane. Hypoxic injury induces the formation of both fluid and rigid lipid domains; the formation of these domains is responsible for loss of the plasma membrane permeability barrier and the onset of irreversible injury (cell death). By defining the mechanisms which lead to alterations in lipid and phospholipid order and organization in the plasma membrane of hypoxic cells, potential sites of intervention to delay, prevent, or rescue cells from hypoxic injury have been identified. Finally, we briefly discuss fluorescence lifetime imaging microscopy (FLIM) and its potential application for studies monitoring local lipid and phospholipid molecular order and organization in cell membranes. PMID- 24226614 TI - Configurational relaxation of "Van Der Waals complexes" in solution. AB - Novel measurements on the microscopic solvation dynamics of 3-amino-N methylphthalimide (3ANMP) in nonpolar decalin (decahydronaphthalene) solutions with small concentrations of ethanol and other polar additives have been made, using the time-dependent fluorescence Stokes shift (TDFSS) technique. It is found that the experimentally measured TDFSS slightly differs from that predicted by the theory of the generalized Smoluchowski-Vlasov equation (SVE). The essentially slower character of the TDFSS in binary solutions than given by the SVE approach may be explained by the control of the solvation behavior by the large-wavevector processes involving nearest-neighbor molecules. PMID- 24226615 TI - Band shape analysis of electronic spectra of polar dye solutions. AB - A semiclassical theory of electronic spectra of polar dye solutions is presented and analytical expressions of the spectra are given. A quasi-molecular approach is applied and the quasi-molecule model of the spectra previously published is reanalyzed. It is assumed that a large-amplitude motion plays a key role in the broadening of the spectra of polar dye solutions. An energy-level diagram of a quasi-molecule, considered as a dye molecule with its nearest neighborhood, is presented. In addition, the energy of reorientation in going from a Franck-Condon to an equilibrated state is determined. The orientation energy is equal to that part of the excitation energy given by the difference of the excited Franck Condon state of a quasi-molecule from that of its equilibrated excited state. It is shown that after excitation, not only is excess vibrational, but also part of the electrostatic interaction energy is transferred to the surroundings. This energy may be obtained directly from absorption and fluorescence spectra of polar dye solutions. Experimental verification is performed on several coumarin solutions. The mean value for the reorientation energy in this case is found to be 645 cm-1. PMID- 24226616 TI - Evidence for an excited-state reaction contributing to NADH fluorescence. AB - The fluorescence of reduced beta-nicotinamide adenine dinucleotide (NADH) was monitored as a function of the excitation and emission wavelengths. In aqueous and organic solvents the intensity decay was found to be more heterogeneous than reported earlier. When the ternary complex of NADH with the enzyme (horse liver alcohol dehydrogenase) and substrate analog (iso-butyramide) is formed, three exponents are required to fit the data. The decay-associated spectrum for the shortest lifetime undergoes a sign change from positive at the blue edge of emission to negative at the red edge. This phenomenon is interpreted as an outcome of reversible excited-state reaction leading to the appearance of at least one fluorescent product. PMID- 24226617 TI - Direct determination of kinetic parameters for diffusion-influenced reactions in solution by analysis of fluorescence decay curves. AB - Fluorescence decay curves were synthesized using the Smoluchowski-Collins-Kimball (SCK) model for diffusion-influenced bimolecular reactions so as to simulate measurements using the technique of time-correlated single photon counting (TCSPC). The experimental conditions required for successful recovery of the parameters used to generate these decay curves were assessed by direct analysis using the decay function associated with the SCK model, where the term "direct analysis" refers to analysis in which all of the fundamental parameters associated with the SCK model are permitted to vary freely. Analysis of decay curves synthesized using an instrument response function measured using a flash lamp TCSPC system and having a full-width at halfmaximum (fwhm) of approximately 2.8 ns was unsuccessful for the values of the parameters associated with the SCK model that were used in this work. However, analysis of these synthesized fluorescence decay curves using the long-time approximation to the SCK model was found to be valid. The results of analysis of fluorescence decay curves synthesized using a 37-ps fwhm instrument response function indicate that the long-time approximation becomes a poor description of the kinetics of diffusion on the time scale associated with these decay curves. Furthermore, direct analysis using the function associated with the SCK model of the synthesized fluorescence decay curves convoluted with this response function and containing 5.0* 10(4) or 1.0 * 10(5) counts in the channel of maximum intensity resulted in the recovery of parameter values that are in very good agreement with those used to generate these decay curves. The results obtained using the simple methodology developed in this work demonstrate for the first time that direct analysis of fluorescence decay curves measured using TCSPC according to the decay function derived from the SCK model can yield reliable estimates for values of the relevant parameters under suitable experimental conditions. PMID- 24226618 TI - Plasma kinetics of injected recombinant chicken somatotropin in juvenile coho salmon (Oncorhynchus kisutch) using a homologous radioimmunoassay. AB - Although somatotropins are potent growth promoters in salmonids, there is little information on how these proteins are metabolized by poikilotherms. In the present study, the plasma uptake and clearance rates of recombinant chicken somatotropin (rcGH) were investigated in juvenile coho salmon (Oncorhynchus kisutch). Two doses of rcGH were administered by intraperitoneal (ip) or intramuscular (im) injection and blood samples were collected over a period of 32 days. A specific radioimmunoassay was validated and used to discriminate rcGH from endogenous somatotropin. Plasma rcGH concentration was proportional to the dose delivered, but uptake and clearance rates were found to be independent of dose (between 0.5 and 5.0 MUg/g). Absorption of rcGH into the plasma was faster from the im site, but the peak levels attained were similar after im or ip treatment (using the same dose) as was area under the curve. Plasma half-life was calculated from the declining phase of the uptake/clearance profile but the results were biased by the concurrent uptake of rcGH from the ip or im reservoir of material, resulting in an over-estimation of the true half-life value. Effective treatment doses and intervals are discussed. PMID- 24226619 TI - An homologous radioimmunoassay for brown trout (Salmo trutta) vitellogenin. AB - An homologous radioimmunoassay for brown trout vitellogenin (VTG) was developed. Intact VTG, isolated from juvenile brown trout by selective precipitation and anion exchange chromatography was labelled with Na(125)I, with 1,3,4,6 tetrachloro-3alpha,6alpha-diphenylglycoluril (Iodogen) as the oxidizing agent. Incorporation of Na(125)I into VTG was higher than 75% and there was little degradation of the labelled protein. Labelled VTG eluted at the same position as unlabelled, purified brown trout VTG when analyzed by gel filtration on Sepharose 6B. Antisera with high titers, i.e. 1?250 000, against brown trout VTG were raised in rabbits. The sensitivity of the assay was 5 ng VTG/ml and the standard curve was linear between 10 and 100 ng VTG/ml. Plasma from maturing female brown trout, as well as estradiol-treated and untreated juvenile brown trout diluted parallel to the standard curve, while plasma from maturing female rainbow trout and estradiol-treated arctic charr diluted non-parallel to the standard curve for brown trout VTG. Purified rainbow trout VTG and plasma from maturing female rainbow trout diluted parallel to each other, but with lower sensitivity than for brown trout VTG. Determinations of protein-bound phosphorus in the plasma of estradiol-treated juvenile brown trout correlated well with the RIA determinations of VTG. Repeated freezing and thawing of plasma samples yielded up to a hundred-fold increase in the apparent VTG level, while storage of a plasma sample for one year at -20 degrees C did not affect the VTG level as measured by RIA. PMID- 24226620 TI - Bilirubin-binding protein in the serum of spawning-migrating chum salmon,Oncorhynchus keta: Its identity with carotenoid-carrying lipoprotein. AB - The serum carotenoid level gradually increased during the spawning migration of chum salmon (Oncorhynchus keta). Zeaxanthin, a yellowish carotenoid, was detected in the serum of spent males, while astaxanthin was a main carotenoid in the serum of males and females at other developmental stages. A high bilirubin level was found in the serum of spent males; the serum of spent male was yellow in colour due to the presence of zeaxanthin and bilirubin, although the serum of the other fish was bright orange.Three types of carotenoid-carrying lipoprotein such as low density lipoprotein, high density lipoprotein (HDL) and very high density lipoprotein fractions were present in the serum. Carotenoid-carrying lipoprotein from the HDL fraction became a main component during spawning migration. The serum bilirubin from the spent male salmon was distributed in the HDL fraction. Because bilirubin, as well as carotenoids, were present in the HDL fraction, the carotenoid-carrying lipoprotein from the HDL fraction was identical with bilirubin-binding protein in the serum of spent males. This carrier lipoprotein had two subunits (molecular weight 24,000 and 12,000); no disulfide bond was detected between the two subunits. PMID- 24226621 TI - Hepatocellular adaptation to extreme nutritional conditions in ide,Leuciscus idus melanotus L. (Cyprinidae). A morphofunctional analysis. AB - The adaptive response of the omnivorous ide,Leuciscus idus melanotus, to drastic metabolic conditions was analyzed on different levels of organisation investigating a variety of parameters: Organism (condition factor, liver-somatic index), organ (liver structure), cellular and subcellular level (hepatocyte structure, glycogen and lipid storage, contents and distribution of nucleic acids, enzyme alterations).During starvation, ide were able to maintain liver integrity in a biphasic process: after an initial phase of disturbance, ide established a new structural and metabolic homeostasis. Recovery from starvation was possible only with a complete diet but not with a sucrose diet. Carbohydrate overload, as evoked by sucrose refeeding, did not result in liver or carcass fattening as known from mammals.To the best of our knowledge, the present study is the first to use enzyme histochemistry in fish nutrition research. In mammals, histochemistry is particularly helpful for understanding processes of hepatic metabolic adaptation. In fish, however, on the basis of our results, enzyme histochemical studies appear to be of limited value, as long as no further data are available on a zonal distribution of enzyme activities in teleost liver parenchyma. Instead, the histochemical detection of the distribution of hepatic storage products and RNA-positive material yielded important information on liver adaptive processes. PMID- 24226622 TI - Characterization of the receptor for gonadotropin-releasing hormone in the pituitary of the African catfish,Clarias gariepinus. AB - Receptors for gonadotropin-releasing hormone (GnRH) were characterized using a radioligand prepared from a superactive analog of salmon GnRH (sGnRH), D-Arg(6) Pro(9)-sGnRH-NEt (sGnRHa). Binding of(125)I-sGnRHa to catfish pituitary membrane fractions reached equilibrium after 2 h incubation at 4 degrees C. Displacement experiments with several GnRH analogs as well as other peptides, demonstrated the specificity of(125)I-sGnRHa binding. Specific binding was enhanced in the presence of the cation chelator ethylene bis (oxyethylenenitrilo) tetra-acetic acid (EGTA), indicating an inhibitory effect of cations on GnRH-receptor binding. The binding of(125)I-sGnRHa to pituitary membranes was found to be saturable at radioligand concentrations of 5 nM and above. A Scatchard analysis of the saturation data suggested the presence of a single class of high-affinity binding sites (Ka=0.901+/-0.06*10(9)M(-1), Bmax=1678+/-150 fmol/mg protein). A comparative study on(125)I-sGnRHa binding to pituitary membrane fractions of male and female catfish, indicated that there were no differences in binding affinity and binding capacity between both sexes. The results demonstrate the presence of specific, saturable GnRH receptors in the African catfish pituitary. PMID- 24226623 TI - Effect of running retraining on pain, function, and lower-extremity biomechanics in a female runner with iliotibial band syndrome. AB - CONTEXT: Iliotibial-band syndrome (ITBS) is a common overuse running injury. There is inconclusive evidence to support current management strategies, and few advances have been made in the past few years. New management approaches should thus be developed and evaluated. OBJECTIVE: To assess the effects of a real-time running-retraining program on lower-extremity biomechanics, pain while running, and function. DESIGN: Single-subject experimental study. SETTING: University motion-analysis laboratory. PARTICIPANT: Female recreational runner with ITBS. INTERVENTION: Nine real-time running-retraining sessions were implemented based on the biomechanical alterations of the participant's symptomatic lower limb, including pelvic and knee movement in the transverse plane, as well as foot movement in the frontal plane. Real-time visual feedback of the pelvic-rotation angle was provided during the running-retraining sessions. MAIN OUTCOME MEASUREMENTS: 3-dimensional lower-extremity running kinematics, pain on a verbal analog scale while running on a treadmill, and the Lower Extremity Functional Scale (LEFS). RESULTS: Pelvic external rotation decreased, although the aim was to increase pelvic external rotation and knee rotation. The foot-progression angle improved after the intervention and at 1-mo follow-up. There was a 12.5% improvement in running time, and the pain score while running improved by 50% postintervention; these improvements were maintained at 1-mo follow-up. The mean LEFS score, indicative of function, improved by 8.75% and by 10% at the end of the intervention and at 1-mo follow-up, respectively. CONCLUSION: The real-time running-retraining program improved pain while running, as well as function, and was effective in addressing the lower-limb biomechanical alterations of the knee and foot in a female runner with ITBS. The application, effectiveness, and feasibility of real-time training should be addressed in larger studies in the future. PMID- 24226624 TI - In situ grafted carbon on sawtooth-like SiC supported Ni for high-performance supercapacitor electrodes. AB - A novel C-Ni-SiC composite using sawtooth-like SiC as support and carbon as modified material was prepared by hydrothermal synthesis and thermochemical pyrolysis. As a supercapacitor electrode, it exhibits very high specific capacitance (1780 F g(-1)) and excellent cycling performance (>96% for 2500 cycles). PMID- 24226625 TI - Tobacco product use among middle and high school students--United States, 2011 and 2012. AB - Nearly 90% of adult smokers in the United States began smoking by age 18 years. To assess current tobacco product use among youths, CDC analyzed data from the 2012 National Youth Tobacco Survey (NYTS). This report describes the results of that analysis, which found that, in 2012, the prevalence of current tobacco product use among middle and high school students was 6.7% and 23.3%, respectively. After cigarettes, cigars were the second most commonly used tobacco product, with prevalence of use at 2.8% and 12.6%, respectively. From 2011 to 2012, electronic cigarette use increased significantly among middle school (0.6% to 1.1%) and high school (1.5% to 2.8%) students, and hookah use increased among high school students (4.1% to 5.4%). During the same period, significant decreases occurred in bidi and kretek use among middle and high school students, and in dissolvable tobacco use among high school students. A substantial proportion of youth tobacco use occurs with products other than cigarettes, so monitoring and prevention of youth tobacco use needs to incorporate other products, including new and emerging products. Implementing evidence-based interventions can prevent and reduce tobacco use among youths as part of comprehensive tobacco control programs. In addition, implementation of the 2009 Family Smoking Prevention and Tobacco Control Act, which granted the Food and Drug Administration (FDA) the authority to regulate the manufacture, distribution, and marketing of tobacco products, also is critical to addressing this health risk behavior. PMID- 24226626 TI - Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. AB - On June 19, 2013, the Advisory Committee on Immunization Practices (ACIP) voted to extend existing recommendations for use of inactivated Vero cell culture derived Japanese encephalitis (JE) vaccine (JE-VC) (Ixiaro, Intercell Biomedical) to include children aged 2 months through 16 years. The ACIP JE Vaccine Workgroup reviewed the epidemiology of JE in travelers and evaluated published and unpublished data on JE-VC immunogenicity and safety in adults and children. The evidence for benefits and risks associated with JE-VC vaccination of children was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and outlines the recommendations for use of JE-VC in children traveling to JE-endemic countries. PMID- 24226627 TI - Notes from the field: late vitamin K deficiency bleeding in infants whose parents declined vitamin K prophylaxis--Tennessee, 2013. AB - Vitamin K deficiency bleeding (VKDB) is a coagulopathy that develops in infants who do not have sufficient vitamin K stores to support production of clotting factors. In adults, vitamin K is absorbed from food and from vitamin K synthesized by gut bacteria. However, placental transfer in humans is limited; cord blood and infant liver reserve levels of vitamin K are substantially below adult levels. As a result, infants are predisposed to develop VKDB, which is classified as early, classic, and late, according to when it presents. In the United States, administration of intramuscular vitamin K at birth to prevent all forms of VKDB has been standard practice since first recommended by the American Academy of Pediatrics in 1961. Without this prophylaxis, incidence of early and classical VKDB ranges from 0.25% to 1.7% of births; incidence of late VKDB ranges from 4.4 to 7.2 per 100,000 infants. The relative risk for developing late VKDB has been estimated at 81 times greater among infants who do not receive intramuscular vitamin K than in infants who do receive it. PMID- 24226628 TI - Notes from the field: primary amebic meningoencephalitis associated with ritual nasal rinsing--St. Thomas, U.S. Virgin islands, 2012. AB - On November 21, 2012, the U.S. Virgin Islands (USVI) Department of Health documented the first case and death from primary amebic meningoencephalitis (PAM) in the territory. PAM, a rare and almost universally fatal condition, results when Naegleria fowleri, a free-living thermophilic ameba found in warm freshwater, enters the nose and migrates to the brain. The patient was a man aged 47 years whose only reported freshwater exposures were the use of tap water for daily household activities and for ablution, a ritual cleansing that he practiced several times a day in preparation for Islamic prayer. Ablution can include nasal rinsing. On November 16, 2012, the patient had visited the emergency department with a headache; he was treated symptomatically and released. The following day, the patient returned to the emergency department by ambulance with fever, confusion, agitation, and a severe headache, for which he was admitted. Cerebrospinal fluid (CSF) studies were consistent with bacterial meningitis, and antibiotics were started. On November 18, neurologic findings included fixed nonresponsive pupils, no response in the upper or lower extremities, muted plantar responses, and no response to verbal commands. Microscopic examination of the CSF obtained from a second lumbar puncture revealed motile amebic trophozoites. CSF specimens sent to CDC for confirmatory testing were positive for N. fowleri by real-time polymerase chain reaction testing. On the morning of November 21, the patient was pronounced brain dead based on neurologic criteria. PMID- 24226629 TI - Notes from the field: outbreak of tuberculosis associated with a newly identified Mycobacterium tuberculosis genotype--New York City, 2010-2013. AB - In January 2010, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) identified a tuberculosis (TB) case caused by Mycobacterium tuberculosis with a genotype not reported previously in the United States. The patient was evaluated for TB while incarcerated but was released before the diagnosis was confirmed and before beginning TB treatment. The patient, who had a history of homelessness and clinical characteristics suggesting infectiousness, could not be located by DOHMH for 13 months. Numerous efforts were made to locate the patient, including queries to shelters, jails, and infection-control staff members at local hospitals. The patient was located after he had an abnormal chest radiograph result following referral by a local jail to a hospital emergency department (ED) for symptoms of alcohol withdrawal; he died from complications of liver cirrhosis 5 days later, without having started TB treatment. During February 2012-May 2013, DOHMH identified four additional patients with the same TB genotype. All five patients were U.S.-born black men aged 52-57 years. Four had a history of substance abuse; three had a history of homelessness; and two had a history of incarceration. All patients had drug-susceptible TB and were negative for human immunodeficiency virus. Three patients completed TB treatment. One patient, who was homeless at the time of diagnosis, began TB treatment but was lost to follow-up by DOHMH. PMID- 24226630 TI - Diagnosis and treatment of mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is a relatively rare lymphoma entity accounting for an estimated 3%-6% of all non-Hodgkin's lymphoma cases. Characterised by both the incurability of indolent lymphomas and the rapid growth of aggressive lymphomas, MCL has a median overall survival of only 4-5 years. Although the disease often shows an encouraging response to first-line treatment, its clinical course is usually marked by recurrent relapses, resulting in a dismal long-term outcome. The choice of therapy for managing the disease is a complex problem that still requires evidence-based guidance. Owing to the rarity of MCL, the bulk of data comes from phase II trials in small numbers of patients. Nevertheless, therapeutic strategies for MCL have evolved in an effort to adapt treatment according to the individual patient's risk profile, and the overall survival has nearly doubled in the last 30 years. The use of effective immunochemotherapy regimens in first-line therapy, advances in stem cell transplantation, and the development of more active salvage therapy regimens have improved the outcome. This review will summarise the key factors that drive clinical practice with respect to the management of MCL. PMID- 24226631 TI - Core-binding factor acute myeloid leukemia in pediatric patients enrolled in the AIEOP AML 2002/01 trial: screening and prognostic impact of c-KIT mutations. PMID- 24226632 TI - Effect of oxygen inhalation on cerebral blood flow velocity in premature neonates. AB - BACKGROUND: The study tested the hypothesis that hyperoxemia and hypoxemia differentially alter cerebral blood flow velocity (CBFV) in a gestational age dependent manner. METHODS: Cases comprised 98 neonates with mild respiratory distress, receiving oxygen for >24 h in first 48 h of life. Ninety-eight age- and weight-matched healthy neonates served as controls. Infants with perinatal asphyxia, shock, sepsis, malformations, acidosis/alkalosis, and hypo/hypercarbia were excluded. Resistance index (RI), pulsatility index (PI), peak systolic flow velocity (PSV), and vascular diameter were measured in internal carotid, vertebral, and middle cerebral arteries by transcranial doppler ultrasonography between 24 and 48 h of life with immediate postdoppler arterial blood gas analysis. For subgroup analysis, neonates were divided by gestational age and PaO2. RESULTS: An overall decrease in RI/PI and increase in PSV and vasodilation was observed in cases. Hyperoxemia (PaO2 >90 mm Hg) was more common in premature neonates. Neonates <32 wk showed an increase in CBFV (decreased RI/PI and increased PSV/diameter) in association with hyperoxemia. An opposite response was observed in neonates >= 32 wk, where CBFV increased in response to hypoxemia (PaO2 <50 mm Hg) and decreased in hyperoxemia. Increased CBFV showed high predictive accuracy for immediate mortality and intracranial hemorrhage. CONCLUSION: Depending on gestational maturity, hyperoxemia or hypoxemia produce differential effects in CBFV. PMID- 24226633 TI - Brain tissue oxygen monitoring identifies cortical hypoxia and thalamic hyperoxia after experimental cardiac arrest in rats. AB - BACKGROUND: Optimization of cerebral oxygenation after pediatric cardiac arrest (CA) may reduce neurological damage associated with the post-CA syndrome. We hypothesized that important alterations in regional partial pressure of brain tissue oxygen (PbO2) occur after resuscitation from CA and that clinically relevant interventions such as hyperoxia and blood pressure augmentation would influence PbO2. METHODS: Cortical and thalamic PbO2 were monitored in immature rats subjected to asphyxial CA (9 or 12 min asphyxia) and sham-operated rats using oxygen sensors. RESULTS: Thalamus and cortex showed similar baseline PbO2. Postresuscitation, there was early and sustained cortical hypoxia in an insult duration dependent fashion. In contrast, thalamic PbO2 initially increased fourfold and afterwards returned to baseline values. PbO2 level was dependent on the fraction of inspired O2, and the response to oxygen was more pronounced after a 9 vs. 12 min CA. After a 12 min CA, PbO2 was modestly affected by blood pressure augmentation using epinephrine in the thalamus but not in the cortex. CONCLUSION: After asphyxial pediatric CA, there is marked regional variability of cerebral oxygenation. Cortical hypoxia is pronounced and appears early, whereas thalamic hyperoxia is followed by normoxia. Compromised PbO2 in the cortex may represent a relevant and clinically measurable therapeutic target aimed at improving neurological outcome after pediatric CA. PMID- 24226634 TI - Targeting intracellular degradation pathways for treatment of liver disease caused by alpha1-antitrypsin deficiency. AB - The classic form of alpha1-antitrypsin deficiency (ATD) is a well-known genetic cause of severe liver disease in childhood. A point mutation alters the folding of a hepatic secretory glycoprotein such that the protein is prone to misfolding and polymerization. Liver injury, characterized predominantly by fibrosis/cirrhosis and carcinogenesis, is caused by the proteotoxic effect of polymerized mutant alpha1-antitrypsin Z (ATZ), which accumulates in the endoplasmic reticulum (ER) of hepatocytes. Several intracellular pathways have been shown to be responsible for disposal of ATZ after it accumulates in the ER, but autophagy appears to be specialized for disposal of insoluble ATZ polymers. Recently, we have found that drugs that enhance the activity of the autophagic pathway reduce the cellular load of mutant ATZ and reverse hepatic fibrosis in a mouse model of ATD. Because several of these autophagy enhancers have been used safely in humans for other reasons, we have been able to initiate a clinical trial of one of these drugs, carbamazepine, to determine its efficacy in severe liver disease due to ATD. In this review, we discuss the autophagy enhancer drugs as a new therapeutic strategy that targets cell biological mechanisms integral to the pathogenesis of liver disease due to ATD. PMID- 24226635 TI - Combined effects of maternal inflammation and neonatal hyperoxia on lung fibrosis and RAGE expression in newborn rats. AB - BACKGROUND: Receptors for advanced glycation end products (RAGE) have been implicated in fibrotic processes. We hypothesized that lung fibrosis induced by maternal lipopolysaccharide (LPS)-mediated inflammation and neonatal hyperoxia involves RAGE in newborn rats. METHODS: Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS or normal saline (NS) on 20 and 21 d of gestation. The pups were reared in room air (RA) or an O2-enrich atmosphere (O2), creating the four study groups, NS + RA, NS + O2, LPS + RA, and LPS + O2. The O2 treatment was >95% O2 for 7 d, followed by 60% O2 for 14 d. RESULTS: Rat pups born to LPS-injected dams exhibited significantly higher lung interferon-gamma and interleukin-1beta (IL-1beta) on postnatal day 7 than the pups born to NS injected dams. Rat pups reared in hyperoxia expressed higher lung IL-10 on postnatal day 7, compared with the RA-reared pups. The LPS + O2 group had significantly higher total collagen and transforming growth factor-beta1 on postnatal days 7 and 21 than the NS+RA group. RAGE mRNA and sRAGE protein expression were significantly lower in the LPS + O2 group on postnatal day 7 than the NS+RA group. CONCLUSION: RAGE may be involved in the pathogenesis of lung fibrosis induced by maternal systemic inflammation and postnatal hyperoxia in rat neonates. PMID- 24226636 TI - Disappearance of cryoproteins in the sera of a patient with SLE after treatment with blisibimod, a novel subcutaneous anti-B cell therapy. PMID- 24226637 TI - Nurse psychologists: A unique group within health psychology. AB - Since the mid-1980s commonalities between nursing and psychology have been explored, with subsequent establishment of a Nursing and Health Psychology Committee within the American Psychological Association's Division 38. A survey was undertaken to study this little-known, unique cadre of individuals with dual preparation in both nursing and psychology. Participants were queried regarding their educational preparations in both disciplines, current employment, theoretical and/or research interests, and current projects. Results of the survey provide information about the characteristics of this group. Dual preparation appears to offer certain advantages for the practice of health psychology. PMID- 24226638 TI - The psychologist's role in assessing and facilitating patients' knowledge of advance directives in medical settings: A preliminary investigation. AB - In a time of budgetary shortfalls in the medical industry, an aging population, and an increased emphasis on health care choices, psychologists are being called upon to administer advance medical directive programs to patients. This study reports preliminary findings from a program to assess and facilitate patients' knowledge of advance directives (ADs) by the Psychology Service at the Ann Arbor VA Medical Center. The participant pool included 243 male veteran patients admitted to medical and surgical wards at the hospital. The intervention included the use of a computer-generated prompt for consultation, which was sent to the psychology staff in response to a patient inquiry regarding ADs. It also involved an increased emphasis on the delivery of written material on ADs by the admissions clerks. The intervention appeared to result in a modest increase in patients' knowledge of advance directives. Suggestions are offered for areas that should be emphasized in future attempts to increase patients' knowledge and utilization of advance directives. PMID- 24226640 TI - The K-BIT: A screen for IQ in six diverse populations. AB - Performance data were collected on the Kaufman Brief Intelligence Test (K-BIT) from a total of 196 individuals from six diverse populations. College students did best, followed closely by closed head-injured adults and their controls; the order of performance then was learning-disabled children, psychiatric patients, and finally, neurosurgical patients in the acute stages of recovery. PMID- 24226639 TI - Psychological distress and well-being in advanced cancer: The effects of optimism and coping. AB - This study examined the relations among optimism, coping, functional status, and psychological adjustment in 75 adults diagnosed with cancer. Both the positive and the negative aspects of psychological adjustment were assessed. All participants had been diagnosed with advanced stages of cancer (i.e., Stages II, III, and IV). Participants completed three assessments across a 4-month time period. Both optimism and coping were associated with psychological adjustment, even after controlling for functional status and prior adjustment. Additionally, optimism and coping were differentially related to distress and well-being. Optimism was strongly and positively associated with well-being and inversely related to distress. Escape-Avoidance coping was positively associated with distress and Accepting Responsibility coping was negatively associated with well being. Comparisons between the current and prior studies indicated that individuals who are diagnosed with more advanced stages of cancer or who have survived bone marrow transplantation exhibit higher levels of optimism than do healthy individuals and individuals with early-stage disease. PMID- 24226641 TI - Psychology and mind-body segregation: Are we part of the problem? AB - Despite advances in behavioral medicine and health psychology, the health care system and medical education continue to show resistance to a truly biopsychosocial model of medical practice. Psychologists in medical settings have generally been identified as challenging the concept of mind-body duality and the segregation of biologic and psychosocial sciences in medicine. However, examples are presented of how psychologists contribute to and perpetuate mind-body segregation via exclusive theoretical conceptualizations, arbitrary definitions of professional behavior, and dogmatic constraints on the limits of psychology's field of knowledge. PMID- 24226642 TI - Establishing psychological services in a community-based, health care setting: A 3-year case study. AB - Health care practitioners are being challenged to reorganize service delivery and psychology providers are emerging as important participants in shaping the development of primary health care practices. The article outlines the 3-year process of a community/academic/health care center partnership to develop a new model for providing interdisciplinary health care services. The authors describe the process of integrating psychological services into an interdisciplinary, primary care community-based health care center, outline specific planning strategies, and identify the roadblocks and barriers encountered. PMID- 24226643 TI - The psychological physician: Semantics and survival. AB - The calls for change in three areas of professional psychology are briefly reviewed, along with the reasons why such changes would be in the best interest of not only psychology but also the consumers of mental health services. Psychology's survival is linked to the implementation of these changes. It is argued that psychology must (1) standardize its education, training, and doctoral degree; (2) expand its scope of practice; and (3) become, legally and otherwise, "psychological physicians," or risk being rolled-over by history. The importance of terminology and semantics is also discussed. Conclusions are drawn and discussed. PMID- 24226644 TI - The psychological physician: Onward to the future. AB - This article considers the future of professional psychology, with particular reference to the scope of practice. Contemporary threats to, and opportunities for, professional psychology are discussed. It is argued that the course of our continuing evolution could lead to our becoming the premier primary behavioral health care profession, as psychological physicians. The prescription privilege agenda is discussed as the next logical step in that evolution. PMID- 24226645 TI - A rose by any other name: Maintaining the name and highlighting the uniqueness of psychology as a health care profession. AB - In this article, we reply to the comments made by Holden and Levant (preceding articles). While we agree with their goals of expanding the scope of practice of psychology, standardizing training, and educating the public and other health care professionals about the field of clinical psychology, we do not agree that changing the discipline's name to "psychological physician" is a necessary or sufficient means to these ends. We outline the bases for our disagreement with the name change proposal and provide other proposals for reaching the goals set forth by Holden and Levant. PMID- 24226647 TI - Ilial crest bone graft transposition as treatment for fracture of the medial femoral trochlear ridge in a dog. AB - This is a report of a fracture of the medial trochlear ridge of the distal femur occurring as a major complication after surgery for medial patellar luxation. To address the complication, a non-vascularized iliac bone graft was collected and fixated with two positional screws to the trochlea. An external skeletal fixator was placed to prevent motion of the stifle joint during the healing period and to reduce the risk for fragment dislodgment. One year after the graft was placed the dog's function was satisfactory. This case report indicates that a non vascularized iliac bone graft provides an alternative for management of fractures of the medial ridge of the distal femur. PMID- 24226648 TI - Stabilities of thiomolybdate complexes of iron; implications for retention of essential trace elements (Fe, Cu, Mo) in sulfidic waters. AB - In aquatic ecosystems, availabilities of Fe, Mo and Cu potentially limit rates of critical biological processes, including nitrogen fixation, nitrate assimilation and N2O decomposition. During long periods in Earth's history when large parts of the ocean were sulfidic, what prevented these elements' quantitative loss from marine habitats as insoluble sulfide phases? They must have been retained by formation of soluble complexes. Identities of the key ligands are poorly known but probably include thioanions. Here, the first determinations of stability constants for Fe(2+)-[MoS4](2-) complexes in aqueous solution are reported based on measurements of pyrrhotite (hexagonal FeS) solubility under mildly alkaline conditions. Two linear complexes, [FeO(OH)MoS4](3-) and [(Fe2S2)(MoS4)2](4-), best explain the observed solubility variations. Complexes that would be consistent with cuboid cluster structures were less successful, implying that such clusters probably are minor or absent in aqueous solution under the conditions studied. The new data, together with prior data on stabilities of Cu(+)-[MoS4](2-) complexes, are used to explore computationally how competition of Fe(2+) and Cu(+) for [MoS4](2-), as well as competition of [MoS4](2-) and HS( ) for both metals would be resolved in solutions representative of sulfidic natural waters. Thiomolybdate complexes will be most important at sulfide concentrations near the [MoO4](2-)-[MoS4](2-) equivalence point. At lower sulfide concentrations, thiomolybdates are insufficiently stable to be competitive ligands in natural waters and at higher sulfide concentrations HS(-) ligands out compete thiomolybdates. PMID- 24226646 TI - Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. AB - BACKGROUND: In sickle cell disease, a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Without intervention, stroke affects around 10% of children with sickle cell anaemia (HbSS) and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso occlusion and stroke. However, side effects can be severe. OBJECTIVES: To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease to prevent first stroke or recurrences. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Date of the latest search of the Group's Haemoglobinopathies Trials Register: 28 January 2013. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with sickle cell disease to alternative or no treatment. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the risk of bias of the included trials and extracted data. MAIN RESULTS: Searches identified three eligible randomised trials (n = 342). The first two trials addressed the use of chronic transfusion to prevent primary stroke; the third utilized the drug hydroxycarbamide (hydroxyurea) and phlebotomy to prevent both recurrent (secondary) stroke and iron overload in patients who had already experienced an initial stroke. In the first trial (STOP) a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% was compared with standard care in 130 children with sickle cell disease judged (through transcranial Doppler ultrasonography) as high risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group, odds ratio 0.08 (95% confidence interval 0.01 to 0.66). This meant the trial was terminated early. The transfusion group had a high complications rate, including iron overload, alloimmunisation, and transfusion reactions. The second trial (STOP II) investigated risk of stroke when transfusion was stopped after at least 30 months in this population. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued as measured by reoccurrence of abnormal velocities on Doppler examination or the occurrence of overt stroke in the group that stopped transfusion. The third trial (SWiTCH) was a non-inferiority trial comparing transfusion and iron chelation (standard management) with hydroxyurea and phlebotomy (alternative treatment) with the combination endpoint of prevention of stroke recurrence and reduction of iron overload. This trial was stopped early after enrolment and follow up of 133 children because of analysis showing futility in reaching the composite primary endpoint. The stroke rate (seven strokes on hydroxyurea and phlebotomy, none on transfusion and chelation, odds ratio 16.49 (95% confidence interval 0.92 to 294.84)) was within the non inferiority margin, but the liver iron content was not better in the alternative arm. AUTHORS' CONCLUSIONS: The STOP trial demonstrated a significantly reduced risk of stroke in participants with abnormal transcranial Doppler ultrasonography velocities receiving regular blood transfusions. The follow-up trial (STOP 2) indicated that individuals may revert to former risk status if transfusion is discontinued. The degree of risk must be balanced against the burden of chronic transfusions. The combination of hydroxyurea and phlebotomy is not as effective as "standard" transfusion and chelation in preventing secondary stroke and iron overload. Ongoing multicentre trials are investigating the use of chronic transfusion to prevent silent infarcts, the use of hydroxyurea as an alternative to transfusion in children with abnormal transcranial Doppler ultrasonography velocities, and the use of hydroxyurea to prevent conversion of transcranial Doppler ultrasonography velocities from conditional (borderline) to abnormal values. PMID- 24226649 TI - Postadmission sepsis as a screen for quality problems: a case-control study. AB - The present on admission (POA) indicator used with diagnosis codes listed in hospital discharge abstracts makes it possible to screen for possible in-hospital complications, which may in turn point to quality of care problems. A case control study was performed among 382 patients from 30 New York State hospitals to see if lapses in quality were associated with the development of postadmission sepsis. Cases with hospital-acquired sepsis (labeled not POA) were compared with matched controls without sepsis. The authors found that central venous catheters and emergently inserted peripheral intravenous catheters were associated with subsequent development of sepsis. Urethral catheters were associated with sepsis for medical patients but not for surgical patients. Adherence to several process of care guidelines was incomplete but none occurred statistically significantly more frequently among sepsis cases than controls. Using discharge abstract diagnosis codes to determine the presence of postadmission complications shows promise for identifying areas for quality improvement. PMID- 24226650 TI - Reduction of central line-associated bloodstream infections in a pediatric hematology/oncology population. AB - This study reports the results of an initiative to reduce central line-associated bloodstream infections (CLABSIs) among pediatric hematology/oncology patients, a population at increased risk for CLABSI. The study design was a pre-post comparison of a series of specific interventions over 40 months. Logistic regression was used to determine if the risk of developing CLABSI decreased in the postintervention period, after controlling for covariates. The overall CLABSI rate fell from 9 infections per 1000 line days at the beginning of the study to zero in a cohort of 291 patients encompassing 2107 admissions. Admissions during the intervention period had an 86% reduction in odds of developing a CLABSI, controlling for other factors. At the study team's institution, an initiative that standardized blood culturing techniques, lab draw times, line care techniques, and provided physician and nurse education was able to eliminate CLABSI among pediatric hematology/oncology patients. PMID- 24226651 TI - Staging for cutaneous squamous cell carcinoma as a predictor of sentinel lymph node biopsy results: meta-analysis of American Joint Committee on Cancer criteria and a proposed alternative system. AB - IMPORTANCE: The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed. OBJECTIVE: To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC. DESIGN, SETTING, AND PARTICIPANTS: Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system. EXPOSURE: Nonanogenital cSCC and SLNB. MAIN OUTCOMES AND MEASURES: Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes. RESULTS: A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system. CONCLUSIONS AND RELEVANCE: Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system. PMID- 24226652 TI - Third Conference on Methods and Applications of Fluorescence spectroscopy, Prague, Czech Republic, October 18-21, 1993. PMID- 24226653 TI - Fluorescence lifetime-based biosensing of zinc: Origin of the broad dynamic range. AB - Fluorescence lifetime-based chemical sensors have recently been described for applications in medicine, environmental monitoring, and bioprocess control. These sensors transduce the level of the analyte as a change in the apparent fluorescence lifetime of an indicator phase. We have previously developed a wavelength-ratiometric fluorescence biosensor for zinc based on binding of zinc and dansylamide to apo-carbonic anhydrase which exhibited high sensitivity and selectivity. We demonstrate that the apo-carbonic anhydrase/dansylamide indicator system is very well suited for lifetime-based sensing, with a subnanomolar detection limit and greater than 1000-fold dynamic range. The theoretical basis for the wide dynamic range is discussed. PMID- 24226654 TI - Diclofenac and naproxen analysis by microbore liquid chromatography (LC) with native fluorescence detection. AB - A microbore LC system applying native fluorescence detection is described for analysis of the nonsteroidal antiinflammatory agents diclofenac and naproxen in pharmaceutical preparations, allowing the visualization of some diclofenac decomposition products. The suggested system is practical and specific and offers detection limits of 0.2 MUg ml(-1) for diclofenac and of 1 pg ml(-1) for naproxen (solutions to be injected). Moreover, the solvent consumption is reduced by a 10 fold factor compared to the classical HPLC setup. PMID- 24226655 TI - Application of a novel lipophilized fluorescent dye in an optical nitrate sensor. AB - A new lipophilic pH probe (1-hydroxypyrene-3,6,8-tris-octadecylsulfonamide) has been synthesized, and its spectral properties and applications in a solid state nitrate sensor are shown. The sensor is investigated with respect to sensitivity, limits of detection, and selectivity over other anions found in drinking water. PMID- 24226656 TI - Fluorescence spectroscopy of polynuclear aromatic compounds in environmental monitoring. AB - The occurrence of polynuclear aromatic compounds (PAC) in the environment and experimental techniques suitable for the detection of PAC in environmental compartments are briefly reviewed. The specific requirements for on-site andin situ environmental analysis are outlined. Particular emphasis is given to fluorescence spectroscopic techniques for the investigation of humic acid- and soil-containing samples. Some examples of studies in the literature on Shpol'skii and jet spectroscopy and on laser-induced fluorescence (OF) measurements of PAC and mineral oils are highlighted. Contaminants in the environment are usually encountered as multicomponent mixtures in very complex matrices. Total fluorescence analysis in combination with the chemometrical technique of rank annihilation factor analysis (RAFA) was employed for the evaluation of a six component PAC mixture in toluene. It was shown that even in the presence of strong spectral overlap the qualitative identification of all compounds and the reliable quantification of five substances was possible. Results are presented from our stationary and time-resolved fluorescence investigations of the interactions between pyrene and humic acid in water. The Stern-Volmer analysis showed a significant effect of pH on the static quenching efficiency which can be explained by the pH-dependent macromolecular structure of humic acids. Preliminary results from studies of the deactivation of triplet PAC and quenching of delayed fluorescence by humic acid are reported. LIF measurements of mineral oils directly from soil surfaces and of a model oil in a soil column were performed with a fiber-optic coupled multichannel spectrometer. The fluorescence intensity/ concentration relationships were established for a crude and a fuel oil; the corresponding lower limits of detection (LOD) were determined to be 0.025 and 0.125% m/m (mass/mass percentages). These detection limits are compared with realistic oil contaminations of soils. In a soil column designed to mimic fixed-bed bioreactors the distributions of fluorescence signal intensities from a perylene-doped model oil before and after water flooding were determined. These results fromin situ measurements can provide a quantitative basis for the modelling of temporal and spatial contaminants' distributions in reactor design. PMID- 24226657 TI - Time-resolved chlorophyll fluorescence of spruce needles under various light conditions. AB - Different branches of a declined spruce were exposed to full sunlight, reduced sunlight (using a fine wire mesh), and natural shadow. Subnanosecond decay kinetics and time-gated fluorescence spectra of individual needles were measured and compared with their chlorophyll concentration. Sunlight-exposed needles showed lower chlorophyll concentrations and higher intensitiesI 3 of a long-lived fluorescent component (decay time about 3 ns) than shadow needles. This seems to be due to a reduced energy transfer from the chlorophyll antenna molecules to the reaction centres of Photosystem II. After light reduction to 15-20% during one summer season the chlorophyll concentration increased, whereasI 3 decreased, thus proving some recovery of the photosynthetic apparatus. PMID- 24226658 TI - Effect of C-H bonds on the quenching of luminescent lanthanide chelates. AB - The quenching of europium(III) and terbium(III) chelate luminescence by high energy C-H vibrational manifolds was studied with two types of stable chelates, i.e., a seven-dentate phenylethynylpyridine derivative and a nine-dentate terpyridine derivative. The replacement of C-H bonds by C-D bonds in the chelating parts of the ligands had a clear positive effect on Eu(3+) luminescence but a negligible effect on Tb(2+) luminescence. In aqueous solution, however, the positive effect was undetectable, if the chelating ligand did not create complete shielding of the ion against aqueous quenching. In chelates, where the coordination of water molecules to the inner sphere is prevented, the residual quenching through C-H vibrational quanta can be avoided by replacement of all C-H bonds in the vicinity of the emitting ion by C-D bonds. PMID- 24226659 TI - Fluorescence yields and molecular orientation of thin organic films: Vapor Deposited Oligothiophenes alpha3T-alpha8T. AB - The fluorescence quantum yields of vapor-deposited (VD) films of alpha oligothiophenes,nT, with ring numbers ofn=3-8 and layer thicknesses ofd=3-50 nm were determined at room temperature andT=77 K and compared to the yields of dilute solutions and small (5T)x clusters. The yields of highly oriented ultrathin films are of the order of PhiF=5*10(-5)-1*10(-4). The yields increase strongly with the layer thickness and also upon cooling, but do not reach the values in dilute solution. The main nonradiative deactivation step S1 -> T1 in solution was quantified by(1)O2 production, the yields of which systematically decrease withn from PhiF (3T) to 0.36 (6T), in contrast to the fluorescence yields, which increase from PhiF=0.01 (2T) to 0.40 (6T). In films or clusters the S1 -> T1 deactivation step must be a very unimportant side reaction: neither(1)O2 nor any signal of triplet-triplet absorption could be positively identified. PMID- 24226660 TI - Time-resolved fluorescence relaxation of 3-methyllumiflavin in polar solution. AB - We have studied the fluorescent properties of a well-defined model flavin compound (3-methyllumiflavin) in a relatively polar solvent like propylene glycol or ethanol. Inhomogeneous spectral broadening effects were directly time-resolved by detection at the extreme blue and red edges of the fluorescence band of 3 methyllumiflavin using excitation in the main absorption band. At the high-energy side of the emission band a rapid decay component (tens of picoseconds) was resolved indicative for the disappearance of the initially prepared, nonequilibrium state with a characteristic dipolar relaxation time. At the low energy side the rise of a solvent relaxed fluorescent species could be time resolved. The wavelength-dependent effects on the dipolar relaxation were abolished when excitation was at the low-energy side of the absorption band. The experimental decays of the flavin "solvate" at different energies of fluorescence and excitation are presented as they represent an easy diagnosis for energy dependent solvation dynamics. Wavelength dependent rotation of 3 methyllumiflavin, examined by fluorescence anisotropy decay, turned out to be absent for 3-methyllumiflavin in propylene glycol between 263 and 293 K, probably because of the small change in dipole moment upon flavin excitation. PMID- 24226661 TI - Specific solvent effects of hydroxylic solvents on the emission properties of ruthenium(ii)tris(2,2'-bipyridyl) chloride. AB - The excited state of Ru(II)[bpy]3 (2+) dissolved in hydroxylic solvents is subject to specific solvent effects, which were hitherto not understood on a quantitative basis. We determined the solvent effects of linear monovalent alcohols on the energy gap law of internal conversion with the help of lifetime and intensity measurements. An on-line method for measurement of the temperature dependence of quantum efficiencies was introduced. A modified Franck-Condon analysis of emission spectra by taking into account the shape of a Morse potential of the involved states was applied to compute excited-state energies. PMID- 24226662 TI - Hydrolysis kinetics of photoexcited 6-methoxyquinoline in aqueous acetonitrile solutions. AB - 6-Methoxyquinoline undergoes pseudo-first-order hydrolysis and its conjugate acid, second-order proton abstraction by hydroxide ion, in the lowest excited singlet state. The proton transfer kinetics in water containing acetonitrile up to a mole fraction of about 0.1 have been evaluated as a function of acetonitrile concentration. At mole fractions above 0.13 of acetonitrile, proton transfer does not occur. At mole fractions below 0.1 steady-state and pulsed-source fluorimetries show the rate constant for hydrolysis to decrease exponentially with the mole fraction of acetonitrile. This is believed to be due to penetration of the aqueous solvent cage of the 6-methoxyquinoline by acetonitrile rather than to specific solvation by the organic cosolvent. The rate of neutralization of the conjugate acid by hydroxide ion is found to vary only slightly and depends on the bulk dielectric properties of the solvent. PMID- 24226663 TI - Specific molecular properties of organic solvents determine the fluorescence depolarization of DPH and TMA-DPH in membranes. AB - In pig liver microsomes and protein-free egg PC liposomes the effects of organic solvent molecules on the fluorescence depolarization of 1,6-diphenyl-1,3,5 hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-hexa-3,5-triene (TMA DPH) were investigated. Aromaticity, alkyl chain length, and stereometry of the solvent molecules are shown to determine the changes of fluorescence depolarization. A concentration-dependent decrease in the fluorescence anisotropy is obtained with aromatic molecules but not with aliphatic molecules. The decrease correlates with the increasing side chain length of alkylbenzenes for both fluorophors and both membrane systems. Benzene in microsomes deviates characteristically from this trend. Measurements of TMA-DPH reveal smaller changes of anisotropy but yield the same qualitative results. Moreover, it is possible to distinguish the effects of the different stereometric properties of the three xylene isomers on the fluorescence anisotropy of DPH. According to their alkyl chain length and their specific stereometry, they exert the strongest fluidizing effect of all solvents investigated. PMID- 24226664 TI - Recovery of lifetime distributions from frequency-domain fluorometry data by means of the quantified maximum entropy method. AB - The new quantified version of the maximum entropy method allows one to recover lifetime distributions with a precise statement of the accuracy of position, surface, and broadness of peaks in the distribution. Applications to real data (2,6-ANS in aqueous solutions of sodium dodecyl sulfate micelles of Beta cyclodextrin) are presented. PMID- 24226665 TI - End-to-end diffusion coefficients and distance distributions from fluorescence energy transfer measurements: Enhanced resolution by using multiple donors with different lifetimes. AB - We describe a method to improve the resolution of donor-to-acceptor distance distributions in molecules which are flexing on the timescale of the fluorescence lifetime. We measured the timedependent donor decays of two donor (D)-acceptor (A) pairs, where the donor lifetimes were substantially different. The donors were an indole residue (5.7 ns) and a naphthalene residue (24.4 ns). The same dansyl acceptor was used for both D-A pairs. The donor decays are complex due to both a distribution of D-A distances and D-A diffusion. Using the donor decay data for each D-A pair alone, it is difficult to resolve both the distance distribution and the D-to-A diffusion coefficient. However, these values are unambiguously recovered from global analysis of the data from both D-A pairs. The increased resolution from the global analysis is apparently the result of the complementary information content of the data for each D-A pair. The shorter lived indole donor provides more information on the time-zero distance distribution because there is less time for D-A diffusion, and the longer-lived naphthyl donor is quenched to a greater extent than indole due to the longer time for diffusion-enhanced energy transfer. Simulations were also used to demonstrate the increased resolution of global analysis with different lifetime donors to obtain distance distribution parameters in the presence of D-A diffusion. PMID- 24226666 TI - Aggregation ofNaja nigricollis cardiotoxin: Characterization and quantitative estimate by time-resolved polarized fluorescence. AB - After purification to homogeneity by Bio-Rex 70 ion exchange chromatography, micromolar solutions ofNaja nigricollis cardiotoxin were found to contain significant amounts of aggregates, as detected by time-resolved polarized fluorescence of its single tryptophan residue. The level of cardiotoxin aggregation depends strongly and reversibly on the protein concentration and pH. However, supplementary reverse-phase HPLC completely suppresses this aggregation, resulting in all cases in fluorescence anisotropy decays characteristic of the pure cardiotoxin monomer. The self-association properties of cardiotoxin, in the presence of a possible cofactor eliminated by the HPLC step, may be functionally relevant, and would deserve further investigation. The physical heterogeneity of the cardiotoxin samples required an appropriate model for the analysis of fluorescence depolarization, which was iteratively improved by comparison with experimental results. In this way, an approximate molar fraction of 10-15% aggregated cardiotoxin at a 90MUM total protein concentration, pH 7, was determined. The fluorescence of the partly aggregated samples is significantly perturbed as compared to the HPLC-treated monomer, indicating that the cardiotoxin aggregate must have an increased average fluorescence lifetime and a strongly decreased initial anisotropy. The decrease in initial anisotropy suggests either an increased mobility of the tryptophan residue upon aggregation or fast energy transfers between residues of different cardiotoxin molecules brought within a short distance in the aggregate. This study illustrates the high sensitivity of the time-resolved fluorescence technique, through both total fluorescence and anisotropy parameters, to low levels of physical or chemical heterogeneity in a protein sample. PMID- 24226667 TI - Fluorescence investigations of pure and mixed evaporated dye layers. AB - Fluorescence spectroscopy is used to investigate energy transfer processes in evaporated layers consisting of several different dyes. In this study films ofN,N'-dimethylperylene-3,4?9,10-bis-dicarboximide (methylperylene pigment, MPP), coevaporated with copper phthalocyanine (CuPc) at varying ratios, and double layers of MPP and CuPc with different thicknesses are investigated. It is shown that energy transfer from MPP to CuPc occurs in both mixed and double layers. The energy transfer leads to a strong quenching of the MPP fluorescence and sensitized CuPc emission in the NIR region. The concentration dependence of the fluorescence quenching in mixed layers can be described by a Stern-Volmer plot. A simple model based on exciton diffusion between MPP molecules toward active quenching centers is used to determine the diffusion length. PMID- 24226668 TI - Simultaneous determination of benomyl and morestan residues in waters by synchronous solid-phase spectrofluorimetry. AB - In this paper a new, sensitive, and simple method for simultaneous determination of pesticides morestan and benomyl at trace levels in waters is reported. Both chemicals, showing native fluorescence in solution at neutral medium, were fixed on C-18 silica gel at pH 1, giving a fluorescent system. The benomyl-morestan silica gel system, after dry, was packed in a 1-mm silica cell and its synchronous fluorescence spectra were recorded at deltalambda=80 nm for determination of benomyl and deltalambda=25 nm for determination of morestan. Measurements of fluorescence were performed at lambda1=289 nm and lambda2=367 nm for benomyl and morestan analysis, respectively. The applicable concentration ranges were from 0.5 to 15.0 ng.ml(-1) for benomyl and from 0.6 to 15.0 ng.ml(-1) for morestan, with relative standard deviations of 1.2 and 1.5% for benomyl and morestan, respectively, being 0.15 and 0.18 ng.ml(-1) its respective detection limits. The method was applied to the simultaneous determination of residues of both pesticides in water of different provenances. PMID- 24226669 TI - A long-wavelength biolabeling reagent based on the oxonol fluorophore. AB - A red fluorescent dye of the oxonol class, bis-[1-(carboxymethyl)barbituric acid (5)]-pentamethinoxonol, has been synthesized and, in the form of the succinimidyl active ester, has been applied to antibody labeling for application to flow cytometry and to imaging of tissue sections. The new dye, named CMOX (for carboxymethyloxonol), shows maximum excitation at 583 nm and emission at 611 nm, with a quantum yield of 0.2 in aqueous buffer and methanol. Antibodies labeled with the new dye show favorable brightness, photostability, and low levels of nonspecific binding. PMID- 24226670 TI - Immunohistochemical investigation of the pituitary of the sturgeon (Acipenser baeri, Chondrostei). AB - An immunohistochemical study of the sturgeon (Acipenser baeri) pituitary was undertaken using antisera directed against hormones from various classes of vertebrates, including the only pituitary hormone available from sturgeon, gonadotrophin. A positive reaction was obtained after application of antisera towards the following hormones 1-24 synthetic ACTH (1-24 ACTH), melanophore stimulating hormone (MSH), ovine prolactin (oPRL), ovine growth hormone (oGH), salmon growth hormone (sGH), carp gonadotrophin (cGTH) and its beta subunit (betacGTH), sturgeon gonadotrophin (aciGTH), carp thyrotrophin (cTSH) and beta subunit of the human thyrotrophin (betahTSH). The results demonstrate that, in general, the sturgeon pituitary resembles that of teleosts as regards the distribution of the different cell types: ACTH and PRL cells in the rostral pars distalis, GTH, TSH and GH cells in the proximal pars distalis and MSH and PAS cells in pars intermedia. In addition to the topographical organization of the sturgeon pituitary, this study provides data on the immunological relationships between sturgeon pituitary hormones and those of other vertebrates. PMID- 24226671 TI - Studies on the effect of air exposure on gill Na(+)/K (+)-ATPase of the marble goby,Oxyeleotris marmorata, a facultative air-breathing fish. AB - Gill and liver microsomal Na(+)/K(+)-adenosine triphosphatase (ATPase) activities, body weight, and several blood parameters were measured in marble gobies held in freshwater, in air on wet filter paper for 7 days and three days after return to freshwater following 7 days in air. During the 7 days in air, body weight, and blood Na(+) and K(+) concentrations remained unchanged. During the same period, however, mean specific activity of the gill ATPase fell 79% while liver ATPase specific activity was unchanged. When these fish were returned to water the specific activity of the gill ATPase returned to values seen in freshwater gobies within 3 days. Several changes were also noted in the characteristics of the ATPase in the fish held in air. PMID- 24226672 TI - Steroid release from separated theca and granulosa layers of Atlantic salmon (Salmo salar) ovarian follicles: the effects of a purified salmon gonadotrophin preparation. AB - Theca and granulosa layers were removed from ovarian follicles of mature Atlantic salmon (Salmo salar) and were separately incubated under sterile conditions with and without a partially purified salmon gonadotrophin preparation (GTH). Aliquots of the incubation media were removed at intervals and analysed for the steroids 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17alpha20betaP), 17alpha hydroxyprogesterone, progesterone, androstenedione, testosterone and oestradiol. The biosynthesis of C19 and C21 steroids was very largely restricted to the thecal tissue and was markedly stimulated in the presence of GTH. Androstenedione (max 65 ng/ml) and testosterone (max 14 ng/ml) were released from the earliest stages of incubation whereas the release of 17alpha-hydroxyprogesterone (max 51 ng/ml) and progesterone (max 5.5 ng/ml) commenced only after a lengthy induction period. A trace (1.0 ng/ml) of 17alpha20betaP was produced by the theca in the presence of GTH but oestradiol was not detected. The granulosa preparations released levels of 17alpha-hydroxyprogesterone and androstenedione only marginally above the detection limits (ca 0.7 ng/ml) and there was little stimulation of output with GTH. Oestradiol (max 4 ng/ml) was released only in the presence of GTH. 17alpha20betaP, progesterone and testosterone were not detected as products of this tissue. These results, together with those derived earlier from incubations of complete follicles support the view that the synthesis of 17alpha20betaP is essentially a two-cell process in which 17alpha hydroxyprogesterone produced in the theca is subject to the action of steroid 20beta-hydroxysteroid dehydrogenase in the granulosa. The temporal pattern of release of steroids in these and earlier experiments is considered in relation to mechanisms of steroid biosynthesis and to their possible roles in oocyte final maturation. PMID- 24226673 TI - Interaction between ovine growth hormone and triiodo-L-thyronine on metabolic reserves of rainbow trout,Salmo gairdneri. AB - Rainbow trout (Salmo gairneri) were given slow-release coconut oil implants which contained triiodo-L-thyronine (T3) and were subsequently administered ovine growth hormone (oGH) (either 0.24 or 2.5 MUg/g body weight) or saline every seventh day for four injections. The purpose of the study was to examine the interactions between oGH and T3 on several aspects of the metabolism in rainbow trout.Trout treated with T3 alone had higher carcass water content, lower liver glycogen, higher plasma T3 levels and lower plasma cholesterol, triglyceride and protein levels compared with the controls implanted with coconut oil implants alone. Trout treated with oGH alone had higher condition factors, lowered carcass total lipid content, elevated liver lipid and RNA content, and elevated plasma T3 and L-thyroxine (T4) levels compared with the coconut oil-implanted and saline injected controls. Trout treated with T3 and oGH had lower liver glycogen content, higher plasma T3 and fatty acid levels and lower plasma T4, cholesterol and triglyceride levels compared with the controls given coconut oil implants and saline injections alone. There were no apparent effects of either hormone alone or in combination on liver: body mass ratios, liver DNA content, liver RNA:DNA ratios, liver RNA:protein ratios, liver protein:DNA ratios and liver protein content.The data suggest an interaction between oGH and T3 as regards the regulation of condition factor, carcass water content, carcass and liver total lipid content, liver RNA content, plasma fatty acid and plasma protein content. PMID- 24226674 TI - Effect of gender and reproductive status on brain catecholamine and indoleamine levels of flagfish (Jordanella floridae). AB - Levels of serotonin, 5-hydroxyindoleacetic acid, tryptophan, noradrenalin and dopamine were determined in whole brains of male (dominant, subordinate, solitary and resting) and female (laying and resting) flagfish (Jordanella floridae) and related to reproductive activity. Levels of serotonin were consistently elevated in sexually active male flagfish, relative to resting males. Dominant males exhibited lower noradrenalin levels than all other groups of fish. Solitary males exhibited higher levels of noradrenalin than dominant males, and were not significantly different from resting males. The lowest levels of tryptophan were apparent in brains of sexually inactive males and females. Neither sex nor reproductive status had a significant impact on 5-hydroxyindoleacetic acid levels. The hatchability of eggs fertilized by solitary males was reduced by over 40% when compared to dominant males. PMID- 24226675 TI - Muscle ammonia stores are not determined by pH gradients. AB - The theory of non-ionic diffusion predicts that ammonia will distribute between intracellular and extracellular tissue compartments according to transmembrane pH gradients. The distribution of ammonia and(14)C-DMO were compared in white muscle and plasma of rainbow trout (Salmo gairdneri) at rest, and following exhaustive exercise. Under both experimental conditions, intracellular ammonia levels far exceeded those predicted by transmembrane pH gradients. Calculated equilibrium potentials for[Formula: see text]) were very close to published resting values of membrane potential Em in fish white muscle. We conclude that NH 4 (+) is permeable across cell membranes and that intracellular ammonia stores are not determined by pH gradients. PMID- 24226676 TI - The effect of size on the mechanical properties of the myotomal-skeletal system of rainbow trout (Salmo gairdneri). AB - The length and mean cross-sectional area of the myotome of rainbow trout,Salmo gairdneri, scale isometrically with total length (L, cm) and L(2) respectively for fish from 5 to 35 cm in length. The net maximum force, (F, kN.m(-2)) developed by a single twitch of thein situ myotome on one side of the body, and measured normal to the hypural complex increased as; F=1.05*10(-3).L(2.6), and maximum lateral velocity (W, m.s(-1)) at the hypural plate as; W=0.29 L(-0.47). Maximum power (P, W) increased as; P=7.64*10(-5).L(3.06). Acceleration rates predicted from these data do not agree well with observations. In addition, except for small fish, predicted maximum speeds differed from those calculated from minimum twitch times of excised muscle blocks and stride length, the popular method for estimating maximum speed. It is suggested that temporal summation of twitches must occur in larger fish. This could provide forces matched to inertial loads which are important in fitness-critical maneuvers. PMID- 24226677 TI - Estimation of the refractive indices of imidazolium-based ionic liquids using their polarisability values. AB - Statistical models have been used to estimate the refractive index of 72 imidazolium-based ionic liquids using the electronic polarisability of their ions as the data for two different mathematical approaches: artificial neural networks, in the form of multi-layer perceptrons, and multiple linear regression models. Although the artificial neural networks and linear models have been able to accomplish this task, the multi-layer perceptron model has been shown to be a more accurate method, thanks to its ability of determining non-linear relationships between different dependent variables. Additionally, it is clear that the multiple linear regression presents a systematic deviation in the estimated refractive index values, which confirms that it is an inappropriate model for this system. PMID- 24226678 TI - Plasmodesmatal distribution and frequency in vascular bundles and contiguous tissues of the leaf ofThemeda triandra. AB - Small and intermediate vascular bundles and contiguous tissues of the leaf blade ofThemeda triandra var.imberbis (Retz.) A. Camus were examined with transmission and scanning electron microscopes to determine the distribution and frequency of plasmodesmata between various cell types. Plasmodesmata are most abundant at the mesophyll/bundle-sheath cell and bundle-sheath/vascular parenchyma cell interfaces, and their numbers decrease with increasing proximity to both thick- and thin-walled sieve tubes. Among cells of the vascular bundles, the greatest frequency of plasmodesmata occurs between vascular parenchyma cells, followed by that of plasmodesmata between vascular parenchyma cells and companion cells, and then by the pore-plasmodesmata connections between companion cells and thin walled sieve tubes (sieve tube-companion cell complexes). The sieve tube companion cell complexes of theT. triandra leaf are not isolated symplastically from the rest of the leaf and, in this respect, differ from their counterparts in theZea mays leaf. However, the thick-walled sieve tubes, like their counterparts inZea mays, lack companion cells and are symplastically connected with vascular parenchyma cells that about the xylem. PMID- 24226679 TI - Microfilament bundles of F-actin inSpirogyra observed by fluorescence microscopy. AB - Microfilament bundles (MFBs) of F-actin were observed by fluorescence microscopy in cells ofSpirogyra treated with rhodamine-phalloidin. Four types of MFBs could be recognized on the basis of locality and appearance: those dispersed in the cytoplasm near the cell surface; those beneath the plasma membrane running parallel to each other; those at the edges of the chloroplast; and those surrounding the nucleus. Each type exhibited a unique behavior during the cell cycle. Microfilament bundles dispersed in the cytoplasm came together at the middle of the cell to form a fibril ring at the mitotic prophase. The fibril ring decreased in diameter, causing the development of a furrow in the protoplast that progressed from the outside to the inside. After the completion of furrowing, the MFBs in the fibril ring dispersed beneath the plasma membrane. Microfilament bundles surrounding the nucleus formed a net-like cage which became invisible at the mitotic anaphase, while MFBs seen at the chloroplast edges persisted there during the cell cycle without changing their position. Parallel MFBs running perpendicular to the long axis of the cell were seen at all stages in the cell cycle. PMID- 24226680 TI - Isolation of functional extensor and flexor protoplasts fromPhaseolus coccineus L. pulvini: potassium induced swelling. AB - Methods are described for the isolation of functional protoplasts from secondary pulvinus tissue (flexor and extensor) and from leaf mesophyll tissue of primary leaves ofPhaseolus coccineus L. Integrity of the protoplasts was shown by vital staining and their ability to evolve oxygen in the light. Extensor-cell protoplasts increased their volume for up to 60% upon addition of 10 mM KCl. This K(+)-induced swelling was accompanied by increased rates of proton extrusion. PMID- 24226681 TI - Differential regulation and tissue-specific distribution of enzymes of phenylpropanoid pathways in developing parsley seedlings. AB - Characteristic enzymes of general phenylpropanoid metabolism (phenylalanine ammonialyase) and of the flavonoid-glycoside and furanocoumarin branch pathways (chalcone synthase and S-adenosyl-L-methionine: bergaptol O-methyltransferase, respectively) were localized immuno-histochemically in cross-sections of various aerial parts of parsley (Petroselinum crispum) at different stages of seedling development. Phenylalanine ammonia-lyase occurred predominantly in epidermal and oil-duct epithelial cells, but was also detectable in other tissue parts. The two pathway-specific enzymes were localized in the epidermis (chalcone synthase) and in oil ducts (bergaptol O-methyl-transferase). High chalcone-synthase concentrations occurred very early in leaf development and then declined. High levels of the methyltransferase were present at all times investigated. The temporal and spatial at all times investigated. The temporal and spatial distribution of all three enzymes is in agreement with the time courses and sites of accumulation of the biosynthetic end products. PMID- 24226682 TI - Studies on the limitations to photosynthesis in leaves of the atrazine-resistant mutant ofSenecio vulgaris L. AB - In leaves of an atrazine-resistant mutant ofSenecio vulgaris the quantum efficiency of CO2 assimilation was reduced by 21% compared to the atrazine susceptible wild type, and at a light level twice that required to saturate photosynthesis in the wild type the CO2 fixation rate in the mutant was decreased by 15%. In leaves at steady-state photosynthesis there was a measurable increase in the reduction state of the photosystem II (PSII) primary quinone acceptor,Q A. Although this would lead to a decreased rate of PSII electron transport and may thus explain the decrease in quantum efficiency, this cannot account for the fall in the maximum rate of CO2 fixation. The atrazine-resistant mutant showed an appreciably longer photosynthetic induction time which indicates an effect on carbon metabolism; however, the response of CO2-fixation rate to intercellular CO2 concentration revealed no differences in carboxylation efficiency. There were also no differences in the ability to perform a State 1-State 2 transition between the atrazine-resistant and susceptible biotypes and no difference in the profiles of phosphorylated thylakoid polypeptides. It is concluded that the alteration of the redox equilibrium between PSII quinone electron acceptors in the atrazine-resistant biotype limits appreciably the photosynthetic efficiency in non-saturating light. Additionally, there is a further, as yet unidentified, limitation which decreases photosynthesis in the resistant mutant under light saturating conditions. PMID- 24226683 TI - Effect of high light intensities on oxygen evolution and the light activation of NADP-malate dehydrogenase in intact spinach chloroplasts. AB - The factors limiting the photosynthetic carbon metabolism of intact spinach (Spinacia oleracea L.) chloroplasts after a high-light pretreatment have been studied. Photosynthetic CO2 fixation was decreased and became more sensitive to the inhibitory effect of the cyclic-electron-flow inhibitor, antimycin A. Depending on the extent of photoinhibition, changing the balance of linear to cyclic electron flow by adding oxaloacetate and antimycin A either did not relieve, or partially relieved the photoinhibitory effect. The decrease in CO2 fixation appeared to be the consequence of either a limitation by photosystem-II activity (in the case of moderate inhibition) or, at least partially an unfavourable balance between the linear and cyclic electron flows (in the case of strong inhibition). The light activation of NADP-malate dehydrogenase (EC 1.1.1.82) was decreased only in the presence of CO2, i.e. when there was strong competition for reducing power; otherwise, it was unaffected by photoinhibitory treatments, in accordance with its low energy requirement. PMID- 24226684 TI - The stromacentre inAvena plastids: an aggregation ofbeta-glucosidase responsible for the activation of oat-leaf saponins. AB - The stromacentre, a particular structure in the plastids of mostAvena species, was isolated from etioplasts ofAvena sativa and then characterized to determine its biological function. When comparing differentAvena species with or without stromacentre, it was shown that the stromacentre, a 63-kDa protein, and saponins (characteristic compounds ofAvena sativa) either occur together or not at all. This linkage was confirmed by demonstrating a transformation of saponins by the isolated stromacentre protein: avenacosides were hydrolyzed to 26-desgluco avenacosides. Therefore, the stromacentre protein had to be regarded as abeta glucosidase. Enzyme assays usingp-nitrophenyl-beta-D-glucopyranoside as substrate showed that thisbeta-glucosidase has a pH optimum at pH 6.0. The calculatedK m value for this substrate was 2.2.10(-3) M. Antibodies against the stromacentre protein inhibitedbeta-glucosidase activity. The determination of the molecular weight of thebeta-glucosidase by sodium dodecyl sulfate-gel electrophoresis showed that it consists of subunits of 63 kDa. After gel electrophoresis under non-denaturing conditions, enzymatically active molecules were shown to consist of at least two of these subunits. Molecules aggregated up to about 10(6) Da also had enzyme activity. Enzyme assays using avenacosides as substrate showed a pH optimum at pH 6.0. The calculatedK m value for this substrate was 1.2.10(-5) M. The high affinity to the avenacosides and the high specificity for the C-26 bound glucose indicate that avenacosides are the natural substrates for thisbeta glucosidase. Assuming that the avenacosides in oat leaves play a role as preformed chemical inhibitory substances against phytopathogenic microorganisms, a model is presented showing the stromacentre with a central role in activating the fungitoxicity of avenacosides. PMID- 24226685 TI - Wheat-germ agglutinin is synthesized as a glycosylated precursor. AB - The biosynthesis and processing of wheat-germ agglutinin (WGA) were studied in developing wheat (Triticum aestivum L. cv. Marshall) embryos using pulse-chase labeling, subcellular fractionation and immunocytochemistry. A substantial amount of newly synthesized WGA was organelle-associated. Isolation of WGA on affinity columns of immobilized N-acetylglucosamine indicated that it was present in a dimeric form. When extracts from embryos pulse-labeled with [(35)S]cysteine were fractionated on an isopycnic sucrose gradient, radioactivity incorporated into WGA was detected at a position coincident with the endoplasmic reticulum (ER) marker enzyme NADH-cytochromec reductase. The WGA in the ER could be slowly chased into the soluble, vacuolar fraction, with a half-life of approx. 8 h. Immunolocalization studies demonstrated the accumulation and distribution of WGA throughout the vacuoles.Four forms of the WGA monomer were characterized using immunoaffinity purification and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In-vitro translation of polyadenylated RNA isolated from developing wheat embryos produced a polypeptide with Mr 21 000. In-vivo labeling of embryos with radioactive amino acids resulted in the formation of a polypeptide of Mr 23 000 and the mature monomer of Mr 18000. When [(3)H]mannose was used in labeling studies, only the polypeptide of Mr 23 000 was detected. In vivo labeling in the presence of tunicamycin yielded an additional polypeptide of Mr 20 000. These results indicate that WGA is cotranslationally processed by the removal of a signal peptide and the addition of a glycan, presumably at the carboxy-terminus (N.V. Raikhel and T.A. Wilkins, 1987, Proc. Natl. Acad. Sci. USA 84, 6745-6749). The glycosylated precursor of WGA is post-translationally processed to the mature form by the removal of a carboxyl-terminal glycopeptide. PMID- 24226686 TI - Blue light promotes ionic current influx at the growing apex ofVaucheria terrestris. AB - Irradiation of the growing apex of the algaVaucheria terrestris Gotz var.terrestris with blue light (BL), which causes a transient acceleration of growth, also causes a large transient increase in inwardly directed current, which was monitored with a vibrating probe. The growing apex is normally the site of an inward current, and the surface of the non-growing, basal part of the coenocytic cell the site of an outward current. Irradiation of the apex causes only a slight increase in current efflux at the basal part of the cell. The BL promoted current influx at the apex (BLCI) usually starts within 10 s after the onset of irradiation, preceding the light-growth response. With BL pulses shorter than 3 min, the BLCI reaches a maximum in about 3 min, and then declines to its original value over the next 3 min. If the BL pulse is longer than 3 min, the BLCI continues until the light is turned off. The threshold energy of the BLCI with broad-band BL is 2-5 J.m(-2), i.e. smaller than for both the light-growth response and phototropic response. The maximum BLCI reaches a value of approx. 5 MUA.cm(-2), equivalent to an influx of 50 pmol.cm(-2).s(-1) of monovalent cations. The effect of red light (RL) is completely different from that of BL: it either causes increases in the inward current of less than 0.3 MUA.cm(-2), or a transient decrease of current. Furthermore, the direction of the RL-induced change is always the same at the apex and trunk, indicating the participation of photosynthesis. Our results indicate that the BLCI is kinetically and spatially related to the light-growth response and the phototropic bending ofVaucheria. It seems to be a necessary step for the phototropic bending. PMID- 24226687 TI - Expression sites and developmental regulation of genes encoding (1->3,1->4)-beta glucanases in germinated barley. AB - Expression sites of genes encoding (1->3,1->4)-beta-glucan 4-glucanohydrolase (EC 3.2.1.73) have been mapped in germinated barley grains (Hordeum vulgare L.) by hybridization histochemistry. A(32)P-labelled cDNA (copy DNA) probe was hybridized to cryosections of intact barley grains to localize complementary mRNAs. No mRNA encoding (1->3,1->4)-beta-glucanase is detected in ungerminated grain. Expression of (1->3,1->4)-beta-glucanase genes is first detected in the scutellum after 1 d and is confined to the epithelial layer. At this stage, no expression is apparent in the aleurone. After 2 d, levels of (1->3,1->4)-beta glucanase mRNA decrease in the scutellar epithelium but increase in the aleurone. In the aleurone layer, induction of (1->3,1->4)-beta-glucanase gene expression, as measured by mRNA accumulation, progresses from the proximal to distal end of the grain as a front moving away from, and parallel to, the face of the scutellum. PMID- 24226688 TI - Phosphorylation of the plasma-membrane H(+)-ATPase of oat roots by a calcium stimulated protein kinase. AB - When plasma-membrane vesicles isolated from oat (Avena sativa L.) root cells were incubated with [gamma-(32)P]ATP, the H(+)-ATPase was found to be phosphorylated at serine and threonine residues. Phosphotyrosine was not detected. Endogenous ATPase kinase activity was also observed in plasma-membrane vesicles isolated from potato (Solanum tuberosum L.) root cells as well as from yeast (Saccharomyces cerevisiae). Identity of the phosphorylated oat root Mr=100 000 polypeptide as the ATPase was confirmed using conventional glycerol density gradient centrifugation to purify the native enzyme and by a new procedure for purifying the denatured polypeptide using reversephase high-performance liquid chromatography. Kinase-mediated phosphorylation of the oat root plasma-membrane H(+)-ATPase was stimulated by the addition of low concentrations of Ca(2+) and by a decrease in pH, from 7.2 to 6.2. These results demonstrate that kinase-mediated phosphorylation of the H(+)-ATPase is a plausible mechanism for regulating activity. They further indicate that changes in the cytoplasmic [Ca(2+)] and pH are potentially important elements in modulating the kinase-mediated phosphorylation. PMID- 24226689 TI - Limitation of photosynthesis by changes in temperature : Factors affecting the response of carbon-dioxide assimilation to temperature in barley leaves. AB - The aim of this work was to examine the effect of abrupt changes in temperature in the range 5 to 30 degrees C upon the rate of photosynthetic carbon assimilation in leaves of barley (Hordeum vulgare L.). Measurement of the CO2 assimilation rate in relation to the intercellular partial pressure of CO2 at different temperatures and O2 concentrations and at saturating irradiance showed that as the temperature was decreased photosynthesis was saturated at progressively lower CO2 partial pressures and that the transition between the CO2 limited and ribulose-1,5-bisphosphate-regeneration-limited rate became more abrupt. Feeding of orthophosphate to leaves resulted in an increased rate of CO2 assimilation at lower temperatures at around ambient or higher CO2 partial pressures both in 20% O2 and in 2% O2 and it removed the abruptness in the transition between the CO2-limited and ribulose-1,5-bisphosphate-regeneration limited rates. Phosphate feeding tended to inhibit carbon assimilation at higher temperatures. The response of carbon assimilation to temperature was altered by feeding orthophosphate, by changing the concentrations of CO2 or of O2 or by leaving plants in the dark at 4 degrees C for several hours. Similarly, the response of carbon assimilation to phosphate feeding or to changes in 2% O2 was altered by leaving the plants in the dark at 4 degrees C. The mechanism of limitation of photosynthesis by an abrupt lowering of temperature is discussed in the light of the results. PMID- 24226690 TI - Abscisic-acid contents and concentrations in protoplasts from guard cells and mesophyll cells ofVicia faba L. AB - The abscisic-acid (ABA) contents of isolated guard-cell protoplasts and mesophyll cell protoplasts fromVicia faba were determined by high-pressure liquid chromatography followed by gas chromatography. The amounts of ABA found immediately after preparation of the protoplasts varied from 90 to 570 amol per guard-cell protoplast, and from 75 to 100 amol per mesophyll-cell protoplast. These contents correspond to concentrations between 36 and 230 MUmol per liter in guard-cell protoplasts and between 2.7 and 3.3 MUmol per liter in mesophyll-cell protoplasts. During exposure of protoplasts to betaine concentrations of 0.3, 0.5, and 0.8 mol.l(-1) at 0 degrees and 20 degrees C for 30 min, ABA contents as well as the fractions of ABA that leaked into the medium remained constant for both protoplast types. There was no evidence for net production of ABA in isolated protoplasts subjected to osmotic stress. PMID- 24226691 TI - Chalcone synthases from spinach (Spinacia oleracea L.) : I. Purification, peptide patterns, and immunological properties of different forms. AB - The two chalcone-synthase forms from leaves ofSpinacia oleracea L. were purified to apparent homogeneity. Antibodies were raised against both proteins in rabbits. The specificity of the antibodies was tested using immunotitration, immunoblotting, and immunoelectrophoresis techniques. The antibodies exhibited exclusive specificity for chalcone synthase and did not discriminate between the two antigens. The homodimeric chalcone synthases had the same subunit molecular weight but differed in their apparent native molecular weights. The peptide maps indicated extensive homology between the proteins. Chalcone-synthase activity was not detected in isolated spinach chloroplasts. Both enzyme forms were present in spinach cell-suspension cultures in which they were induced by light. PMID- 24226692 TI - Chalcone synthases from spinach (Spinacia oleracea L.) : II. Immunofluorescence and immunogold localization. AB - The distribution of the two chalcone synthases in leaves ofSpinacia oleracea L. was studied at both the tissue and the subcellular level using immunofluorescence and immunogold techniques. Neither technique differentiated between the two enzyme forms. The chalcone synthases are located in the upper and the lower epidermis and to a minor extent in the subepidermal layers. Traces of the two enzyme forms may be present in the residual mesophyll. This distribution is independent of leaf age. A similar distribution of chalcone synthase among tissues was observed in parsley, pea, and bean. Chalcone synthase is also present in guard cells. The spinach chalcone synthases are cytosolic enzymes, and are not associated with tonoplast or endoplasmic reticulum. A small fraction of the chalcone synthases is located in the stroma of the chloroplasts. PMID- 24226693 TI - The effect of humidity and light on cellular water relations and diffusion conductance of leaves ofTradescantia virginiana L. AB - Turgor (Psip) and osmotic potential (Psis) in epidermal and mesophyll cells, in situ xylem water potential (Psi-xyl) and gas exchange were measured during changes of air humidity and light in leaves ofTradescantia virginiana L., Turgor of single cells was determined using the pressure probe. Sap of individual cells was collected with the probe for measuring the freezing-point depression in a nanoliter osmometer. Turgor pressure was by 0.2 to 0.4 MPa larger in mesophyll cells than in epidermal cells. A water-potential gradient, which was dependent on the rate of transpiration, was found between epidermis and mesophyll and between tip and base of the test leaf. Step changes of humidity or light resulted in changes of epidermal and mesophyll turgor (Psip-epi, Psip-mes) and could be correlated with the transpiration rate. Osmotic potential was not affected by a step change of humidity or light. For the humidity-step experiments, stomatal conductance (g) increased with increasing epidermal turgor.Deltag/Psip-epi appeared to be constant over a wide range of epidermal turgor pressures. In light step experiments this type of response was not found and stomatal conductance could increase while epidermal turgor decreased. PMID- 24226694 TI - Iron assimilation in plants: reduction of a ferriphytosiderophore by NADH:nitrate reductase from squash. AB - NADH:nitrate reductase (EC 1.6.6.1) from squash (Cucurbita maxima Duch., cv. Buttercup) can catalyze the reduction of a ferriphytosiderophore from barley (Hordeum vulgare L. cv. Europa). Maximal activity occurs at pH 6, with an apparentK m andV max of 76 MUM and 21 nmol.min(-1).(mg protein)(-1), respectively. The ferriphytosiderophore strongly inhibits nitrate reduction catalyzed by nitrate reductase at the optimal pH for nitrate reduction, i.e. 7.5. On the contrary, nitrate is a poor inhibitor of ferriphytosiderophore reduction catalyzed by nitrate reductase at the optimal pH for this reaction, pH 6.0. Thus, squash has the potential to assimilate the iron from a ferriphytosiderophore synthesized by another plant. PMID- 24226695 TI - A method for separating PEGylated Au nanoparticle ensembles as a function of grafting density and core size. AB - After ligand exchange with PEG, Au NPs with differently mixed surface functionalities co-exist in the as-synthesized sample. It is found that the poorly grafted nanoparticles can be simply removed using a chromatographic method, and the well grafted nanoparticles can be eluted as a function of the core size. PMID- 24226696 TI - Effects of long-term preservation on growth and productivity of Panax ginseng and Catharanthus roseus cell cultures. AB - Cell cultures of Panax ginseng and Catharanthus roseus producing secondary metabolites were preserved in liquid nitrogen or under mineral oil for six months. The growth behaviour and the ability of the cultures to produce ginsenosides or indole alkaloids were measured after a recovery period and compared with cultures maintained by frequent subcultivation during the same period. Neither growth kinetics nor the degree of vacuolization during growth were affected by the long term preservation. Some changes in secondary metabolism were however found, indicating that preservation under mineral oil does not preserve the productivity of cell cultures whereas the cryogenic method does. PMID- 24226697 TI - Cryopreservation of isolated mint shoot tips by vitrification. AB - Shoot tips isolated from a mint clone, Mentha aquatica x M. spicata, were gradually exposed to a mixture containing 35% ethylene glycol, 1 M dimethylsulfoxide and 10% polyethylene glycol-8000 and then immersed into liquid nitrogen. Cooling and warming rates were approximately 4800 degrees C/min and 9000 degrees C/min respectively. Survival after liquid nitrogen treatment ranged from 31% to 75% among experiments. There was no obvious reason for this variation. In many cases the treated shoot tip directly developed into a shoot without any or with only slight callus formation. PMID- 24226698 TI - Triterpenoid biosynthesis in tissue cultures of Glycyrrhiza glabra var. glandulifera. AB - The incorporation of [1-(14)C]acetate and [2(14) C]mevalonate into free and esterified triterpen-3-ols was examined in original plant organs and tissue cultures of Glycyrrhiza glabra var. glandulifera. Both substrates labeled beta amyrin, an oleanane-type triterpene, and cycloartenol and 24 methylenecycloartanol, both of which are intermediates of phytosterol biosynthesis. The label in esterified triterpenes was distributed mainly in phytosterol intermediates, but not in beta-amyrin. The ratio of betaamyrin formation among the three triterpenes from [2-(14)C]mevalonate was relatively high in stolon segments and in root cultures, but negligible in callus cultures. Administration of a specific inhibitor of squalene-2, 3-epoxide:cycloartenol (lanosterol) cyclase caused a marked increase of beta-amyrin synthesis in root suspension cultures, and of 24-methylenecycloartanol synthesis in cell suspension cultures, from [2-(14)C]mevalonate. PMID- 24226699 TI - The transfer of 'Polima' cytoplasmic male sterility from oilseed rape (Brassica napus) to broccoli (B. oleracea) by protoplast fusion. AB - Protoplast fusion was utilised to transfer Polima type cytoplasmic male sterility (CMS) from Brassica napus, canola cv. Polima Karat (Pol-Karat) to B. oleracea, broccoli, var. "Green Comet". Southern and RFLP analysis confirmed that four cybrids possessed nuclear genomes of broccoli with Polima mitochondria and chloroplasts. A fifth cybrid was a nuclear hybrid between broccoli and Pol-Karat, with Polima mitochondria and chloroplasts of broccoli. The broccoli type cybrids were morphologically similar to "Green Comet", while the hybrid type was an intermediate of the two fusion parents. Flowers on the cybrids were distinctive in that although they possessed a morphology typical of Polima, they had very reduced petals. The broccoli type cybrids exhibited some female fertility, albeit low, establishing potential for F1 hybrid production. PMID- 24226700 TI - Stable transformation of papaya via microprojectile bombardment. AB - Stable transformation of papaya (Carica papaya L.) has been achieved following DNA delivery via high velocity microprojectiles. Three types of embryogenic tissues, including immature zygotic embryos, freshly explanted hypocotyl sections, and somatic embryos derived from both, were bombarded with tungsten particles carrying chimeric NPTII and GUS genes. All tissue types were cultured prior to and following bombardment on half-strength MS medium supplemented with 10 mg 1(-1) 2,4-D, 400 mg 1(-1) glutamine, and 6% sucrose. Upon transfer to 2,4-D free medium containing 150 mg 1(-1) kanamycin sulfate, ten putative transgenic isolates produced somatic embryos and five regenerated leafy shoots. Leafy shoots were produced six to nine months following bombardment. Tissues from 13 of these isolates were assayed for NPTII activity, and 10 were positive. Six out of 15 isolates assayed for GUS expression were positive. Three isolates were positive for both NPTII and GUS. PMID- 24226701 TI - Effect of AgNO3 and aminoethoxyvinylglycine on in vitro shoot and root organogenesis from seedling explants of recalcitrant Brassica genotypes. AB - The presence of 1-10 MUM aminoethoxyvinylglycine (AVG) or 5-30 MUM AgNO3 markedly enhanced shoot regeneration from cotyledon and hypocotyl cultures of eight recalcitrant Brassica campestris and B. juncea genotypes tested. Expiants of B. campestris ssp. chinensis and ssp. parachinensis grown with a high AVG concentration (20 MUM), regenerated poorly. All cytokinins tested were equally effective in promoting shoot formation, except that kinetin was inhibitory to shoot regeneration from hypocotyls of B. campestris ssp. pekinensis (cv. Wong Bok). Both AgNO3 and AVG had no effect on percent rooting and number of roots per rooted cutting of Wong Bok, White Sun and Leaf Heading, but AgNO3 was inhibitory to rooting of India Mustard. However, root elongation of all cuttings was markedly inhibited by AVG at concentrations of 5 and 10 MUM. PMID- 24226702 TI - Plant regeneration from cotyledon protoplasts of Xinjiang muskmelon. AB - Cotyledon protoplasts were isolated from seedlings of Xinjiang muskelon (Cucumis melo var.saccharinus) grown under sterile conditions and cultured in modified Miller medium. High frequency division of the protoplast-derived cells was observed. Agarose bead culture with B6S3 tobacco crown gall nurse cells was found most suitable for the cotyledon protoplasts when compared with other culture methods. Intact plants were regenerated from the protocalli by a two-step culture procedure with liquid and then solid media. PMID- 24226703 TI - Somatic embryogenesis and plant regeneration in Triticum aestivum x Leymus angustus F1 hybrids and the parental lines. AB - Somatic embryos and plants were produced from cultured inflorescence and leaf segments of Triticum aestivum X Leymus anaustus F1 hybrids and the parental lines. Inflorescences showed a better capacity for somatic embryogenesis and plant regeneration than leaves. Leymus anaustus produced the highest number of embryogenic calli, while the hybrids were intermediate between this species and Triticum aestivum. Presence of 2,4-D was shown to be essential for induction and maintenance of somatic embryogenesis. Addition of five amino acids (glutamine, proline, asparagine, aspartic acid and glutamic acid) did not have any marked effect when they were used in the callus induction medium. The regenerated plants had the same morphology as the original plants. No cytological modification was observed in the examined plants. PMID- 24226704 TI - Direct gene transfer to plant protoplasts by mild sonication. AB - A novel procedure employing mild sonication for transformation of plant protoplasts is described. Transient expression of a chloramphenicol acetyltransferase (CAT) gene in protoplasts of sugar beet (Beta vulgaris L.) and tobacco (Nicotiana tabacum L.) was obtained by a brief exposure of the protoplasts to 20 kHz ultrasound in the presence of plasmid DNA. Maximum levels of CAT activity were achieved by sonication for 500-900 ms at 30-70 W electric power (0.65-1.6 W/cm2 acoustic power). This reduced the viability to 15-20 % and 60 % for sugar beet and tobacco protoplasts, respectively. Up to 12 % (sugar beet) and 81 % (tobacco) of maximum transient expression could be achieved with no significant loss of viability. Protoplasts surviving exposure to ultrasound were found to have a similar long-term viability and to regenerate to micro-calli as untreated protoplasts. Plasmid DNA concentrations of 80-110 MUg/ml and sucrose concentrations of 21-28 % in the sonication medium were found to be optimal for transient expression. PMID- 24226705 TI - Partial purification and characterization of phytases from pollen of lily (Lilium longiflorum Thunb.). AB - Two phytases from lily pollen (Lilium longiflorum Thunb.) were partially purified and characterized. The first (pH optimum 5.0) was purified 40-fold from ungerminated pollen. The second (pH optimum 6.5) appeared during germination and was purified 68-fold from pollen germinated 2 h. Molecular weight of the first was 72 kD, and the second was 36 kD as determined by gel filtration. Both were active against phosphate esters other than phytate, although purification of the first reduced its activity against AMP and myo-inositol 2-P to 10% of activity against phytate. Phytase from germinated pollen (but not ungerminated) was inhibited by the sulfhydryl agent parahydroxy mercuribenzoate; P i inhibited phytase from ungerminated but not germinated pollen. Such different catalytic and physical properties may reflect different biochemical functions. PMID- 24226706 TI - Efficient plant regeneration from rice protoplasts in general medium. AB - We established an efficient and reproducible procedure for protoplast propagation and fertile plant regeneration of rice (Oryza sativa L.) cultivars Nipponbare and Taipei 309. Selection of scutellum-derived secondary calli, the use of General medium and nurse culture were all found to be critical in the procedure. When 5 basal media (Murashige and Skoog, RY-2, modified R2, Amino Acid and General media) were compared, suspension callus growth rate, protoplast yield and plating efficiency were all about 30% higher in General medium than in the second-best R2 medium. Only one month was required to develop suspension cultures for protoplast isolation using General medium. A plating efficiency as high as 17% and a plant regeneration frequency of 67% were achieved by the improved procedure. Agronomic traits of protoplast- and seed-derived plants were found to be similar. PMID- 24226707 TI - Calcium increases the yield of somatic embryos in carrot embryogenic suspension cultures. AB - An upward shift in the concentration of calcium present in the medium during somatic embryogenesis increased the number of embryos produced approximately two fold. This was observed when embryogenic suspension cells grown in 2,4-D medium with the normal calcium concentration of 10(-3) M were transferred to hormone free medium containing 10(-2) M calcium and when embryogenic suspension cells grown in 2,4-D medium containing 10(-4) M calcium were transferred to hormone free medium with 10(-3) M calcium. At calcium concentrations between 6.10(-3) and 10(-2) M globular stage somatic embryos were found in cultures supplemented with 2.10(-6) M of 2,4-D indicating that elevated calcium counteracts the inhibitory effect of 2,4-D on somatic embryogenesis. No qualitative changes were found in the pattern of extracellular polypeptides as a result of growth and embryogenesis in media with different calcium concentrations. PMID- 24226708 TI - Beet necrotic yellow vein virus coat protein-mediated protection in sugarbeet (Beta vulgaris L.) protoplasts. AB - Transformed Beta vulgaris L. suspension cultures were obtained after cocultivation of sugarbeet cells with Agrobacterium tumefaciens harbouring a binary vector containing the coat protein gene of beet necrotic yellow vein virus inserted between the kanamycin resistance gene and a beta-glucuronidase reporter gene. Protoplasts were isolated both from untransformed cells, and from transformed cells expressing the viral coat protein, and both were then infected with beet necrotic yellow vein virus. Comparison of the levels of infectivity shows that the expression of the coat protein gene in sugarbeet protoplasts mediates high levels of protection against infection by beet necrotic yellow vein virus. PMID- 24226709 TI - Plant regeneration in vitro of South Pacific taro (Colocasia esculenta var. esculenta cv. Akalomamale, Aracea). AB - Axillary bud expiants from South Pacific (Solomon Islands) taro, Colocasia esculenta var. esculenta cv. Akalomamale (Araceae) cultured on a modified Murashige-Skoog medium containing 1 mg NAA 1(-1) and TE formed callus and produced multiple plantlets. Explants died if NAA was present at levels lower than 0.1 mg 1(-1). BA was not required and may have been inhibitory. Plantlets developed faster and became larger following transfer to a hormone-free medium two weeks after the start of culture. Fully grown plants were established in a potting mix and are growing well in a greenhouse. PMID- 24226710 TI - Low-cost solar cell based on a composite of silicon nanowires and a highly conductive nonphotoactive polymer. PMID- 24226711 TI - A randomized, double-blind, placebo-controlled trial to assess the essentiality of acid inhibitors for abdominal pain after gastroscopic mucosal biopsy. AB - BACKGROUND/AIMS: Gastroscopy and gastroscopic mucosal biopsy techniques have become increasingly used as of late for evaluating symptoms presumed to be originated in the upper gastrointestinal tract. Patients often complain however of abdominal pain post-gastroscopic mucosal biopsy, and this study aimed to explore the necessity of acid inhibitors when abdominal pain worsened. MATERIALS AND METHODS: In this randomized, double-blinded, placebo-controlled study, we screened 272 participants, and ultimately enrolled 200 into the study. These 200 participants were randomly assigned in a 1:1 ratio to receive acid inhibitors (esomeprazole, treatment group, n=100; dose,20 mg/d) or matched placebo (control group, n=100) for 3 days post-gastroscopic mucosal biopsy. The presence of abdominal pain was observed pre-and post-gastroscopy, and the therapeutic effect of esomeprazole was assessed. This study was registered at the Chinese clinical trial registry as ChiCTR-TRC-00000500. RESULTS: Ten subjects were lost to followup (4 in treatment group; 6 in the control group). There was no significant difference in the number of subjects with aggravating abdominal pain (treatment 29.2% vs. control 22.3%; p>0.05) between the two groups. Esomeprazole did not significantly (p>0.05) affect the rate of abdominal pain within 24 h (treatment 27.1% vs. control 19.1%), 48 h (treatment 40.6% vs. control 27.7%), and 96 h (treatment 43.8% vs. control 34.0%) on abdominal pain in all in the evaluated subjects. Between the two groups however, a statistically significant difference (p<0.05) was found on overall effective treatment rates at 48 h (treatment 92.9% vs. control 66.7%) and at 96 h (treatment 100% vs. control 81%) in the subjects with worsened abdominal pain. CONCLUSIONS: The study suggests that routine prophylaxis with acid inhibitors is not recommended for all patients post gastroscopic mucosal biopsy, however acid inhibitors should be administered for patients with aggravating abdominal pain. PMID- 24226712 TI - Acid buffering effects of aqueous leaf extract of Ocimum gratissimum L. in the rabbit stomach. AB - BACKGROUND/AIMS: Although the gastroprotective properties of Ocimum gratissimum L. have been mentioned, the exact mechanism is yet to be explored. Since acid output plays a significant role in the pathogenesis of gastric ulceration, the present study was aimed at investigating the effect of leaf extract of Ocimum gratissimum on gastric luminal pH, acid output, parietal cell mass and gastric mucous cell population in rabbits. MATERIALS AND METHODS: The model of pyloric ligation for acid secretion and ulcer study was employed. Prior to the 4 h ligation, male New Zealand rabbits were treated orally with 75 mg/kg, 150 mg/kg and 250 mg/kg b.w aqueous leaf extract of Ocimum gratissimum twice daily for three weeks. The antisecretory and antiulcer effect of Ocimum gratissimum was compared with omeprazole (20 mg/kg p.o). Parietal cell mass and gastric mucous cell population were determined in the gastric samples by histometry. RESULTS: Aqueous leaf extract of Ocimum gratissimum caused significant reduction in ulcer formation, gastric secretion volume and acid output in a dose dependent manner (p<0.05). Percentage inhibition was recorded as 29%, 46.2%, 52.9% for ulcer; and 16.2%, 35.9%, 52.1% for acid output upon pretreatment with 75 mg/kg, 150 mg/kg and 250 mg/kg b.w respectively. Parietal cell mass was also reduced while gastric mucous cell population and luminal pH increased accordingly when compared to the control group. Data were comparable with the antisecretory effect of omeprazole. CONCLUSION: The results indicate that the anti-secretory activity of Ocimum gratissimum may be the anti-ulcer mechanism of this plant. PMID- 24226713 TI - Investigation of ErbB-2 overexpression on patients with gastric cancer in Eastern Anatolia of Turkey. AB - BACKGROUND/AIMS: In the present study, the frequency of ErbB-2 overexpression and its relationship with pathologic parameters on patients with gastric cancer in Eastern Anatolia of Turkey was studied. MATERIALS AND METHODS: A total of 32 newly diagnosed patients were enrolled in the study. DNA isolation was performed on paraffinized tumor tissues obtained from patients by endoscopy or surgical resection. ErbB-2 overexpression was investigated from the isolated DNA by "Real Time Polymerase Chain Reaction". RESULTS: ErbB-2 positivity was detected in five (15.6%) of 32 gastric cancer patients. The correlation between distant metastases and ErbB-2 positivity was found to be statistically significant (p=0.04). Additionally, no statistically significant correlation was noted between ErbB-2 positivity and parameters such as level of differentiation (p=0.7), the depth of tumor invasion (p=0.08), lymph node metastases (p=0.6), Lauren's classification (p=0.4), World Health Organization classification (p=0.3), tumor, node, metastasis staging (p=0.3) and tumor localization (p=0.2). Lymph node involvement was present in all ErbB-2 positive patients, the depth of tumor invasion was T3 (one case) and T4 (four cases) with the cardia being the most common location, which was remarkable, though not statistically significant (p>0.05). All ErbB-2 positive patients were detected with intestinal-type gastric cancer according to Lauren's classification and with the tubular-type according to World Health Organization classification. CONCLUSION: According to our findings, given the rates of ErbB-2 overexpression (15.6%) in gastric cancer, the investigation of ErbB-2 overexpression as an important biomarker in humanized monoclonal-antibody treatment in patients with gastric cancer was considered appropriate. PMID- 24226714 TI - The role of second-look endoscopy in endoscopic submucosal dissection for early gastric cancer. AB - BACKGROUND/AIMS: Delayed bleeding is a major complication of endoscopic submucosal dissection. Second-look endoscopy is routinely performed in most hospitals to reduce the possibility of delayed bleeding without solid evidence to support this practice. The aim of this study was to evaluate whether second-look endoscopy prevents delayed bleeding, and to verify clinicopathological features of delayed bleeding in order to identify lesions that may benefit from a second look endoscopy. MATERIALS AND METHODS: We investigated 392 lesions in 388 patients who underwent endoscopic submucosal dissection for early gastric cancer from January 2006 to July 2011. Clinically evident bleeding from mucosal defects 24 hours after endoscopic submucosal dissection was considered delayed bleeding. Data including characteristics of patients, lesions, and procedures were reviewed. Furthermore, the rate of delayed bleeding before and after second-look endoscopy, performed within three days of endoscopic submucosal dissection, was investigated to determine the utility of second-look endoscopy. RESULTS: Delayed bleeding was evident in 12 of 392 lesions (3,1%), all of which achieved endoscopic hemostasis. The only significant factor predicting delayed bleeding was a resected specimen size of over 40 mm (OR=6,200, 95% CI=1,912 - 20,108). Delayed bleeding occurred more frequently prior to the second-look endoscopy (p=0,022). CONCLUSIONS: In our endoscopic submucosal dissection data about early gastric cancer, it is too early to conclude that second-look endoscopy is not a valuable procedure, and second-look endoscopy may be useful for preventing post endoscopic submucosal dissection bleeding, especially in resected specimens greater than 40 mm in size. PMID- 24226715 TI - Iloprost reduces colitis induced oxidative stress: An experimental study in rats. AB - BACKGROUND/AIMS: Reactive oxygen species have a known potent role in the pathogenesis of ulcerative colitis. Iloprost, a pharmaceutical, is a chemically stable derivative of a naturally- occurring human prostacyclin. Several studies have demonstrated protective effects of iloprost via its antioxidant and its anti inflammatory activity. The aim of this study is to evaluate the effects of iloprost on oxidant/antioxidant status, as well as the large bowel histopathology in experimental colitis. MATERIALS AND METHOD: Forty adult male Wistar-albino rats were randomly divided in to four equal weight-matched groups: sham group (n=10), iloprost administered sham group (n=10), colitis group (n=10), iloprost administered colitis group (n=10). Acetic acid (1 ml of 4% solution) was used to induce colonic inflammation in the rats. RESULTS: Colonic tissue and plasma malondialdehyde levels were significantly lower in the iloprost administered colitis group than the colitis group (p<0.01). Tissue glutathione levels of the iloprost administered colitis group were significantly higher than the colitis group (p<0.001). CONCLUSION: We have demonstrated in this study iloprost to be an antioxidant, as well as iloprost demonstrating protective activity against colitis induced oxidative stress. PMID- 24226716 TI - Comparison of the forty-eight week efficacy between telbivudine and entecavir in HBeAg-positive Asian patients with chronic hepatitis B: A meta-analysis. AB - BACKGROUND/AIMS: Telbivudine and entecavir are two pharmacologic agents recommended and also widely used for the treatment of chronic hepatitis B in most Asian countries. There are few conclusive results when comparing the efficacy of these two drugs for the treatment of chronic hepatitis B. The aim of this study is to evaluate, by means of meta-analysis, the short-term efficacy between the two drugs in nucleos(t)ide-naive Asian HBeAg-positive chronic hepatitis B patients. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Wanfang Database and CNKI (National Knowledge Infrastructure). Twelve eligible trials (1011 patients in total) were included into this study, and they were evaluated for quality and heterogeneity. RESULTS: Meta-analysis date showed the rate of HBeAg clearance and rate of HBeAg seroconversion in the telbivudine group was higher than the entecavir group, respectively. There was no statistically significant difference however between the two groups in the rate of alanine aminotransferase normalization, or the rate of HBV DNA suppression. Although creatine kinase elevations occurred more frequently in the telbivudine group than when compared to the entecavir group, there was no statistically significant difference between the two groups in the short-term treatment duration. CONCLUSIONS: For the short-term treatment of HBeAg positive nucleos(t)ide-naive Asian patients with chronic hepatitis B, telbivudine is as potent as entecavir in normalizing alanine aminotransferase and suppressing HBV DNA, and telbivudine is superior to entecavir in clearing HBeAg and developing anti-HBe. Careful monitoring is needed to avoid adverse events, as well as drug resistance during antiviral therapy with telbivudine. PMID- 24226717 TI - Increased bile lithogenicity by SCP2 via HMGCR and CYP7A1 regulation in human hepatocytes. AB - BACKGROUND/AIMS: Lithogenic bile is a major cause of cholesterol gallstones, and hypersecretion of biliary cholesterol is believed to be an important cause of lithogenic bile. Sterol carrier protein 2 plays a key role in cholesterol trafficking and may regulate lipid metabolism in hepatocytes. MATERIALS AND METHODS: Human sterol carrier protein 2 cDNA was cloned and shRNAs against sterol carrier protein 2 were synthesized. Sterol carrier protein 2-modified hepatocyte models were then set up using adenoviral vectors to study its regulatory function in lipid metabolism. Following overexpression and knockdown of sterol carrier protein 2, HMGCR and CYP7A1 expression as well as the secretion of bile lipids were studied in hepatocytes. RESULTS: The expression of HMGCR was enhanced by sterol carrier protein 2 overexpression and downregulated by sterol carrier protein 2 knockdown. The concentration of cholesterol in the supernatant was elevated under sterol carrier protein 2 overexpression and decreased under sterol carrier protein 2 downregulation. Although sterol carrier protein 2 overexpression could repress the expression of CYP7A1, no changes were noted in total bile acid concentration. Thus, the expression of sterol carrier protein 2 could influence bile lithogenicity in the sterol carrier protein 2-modified hepatocyte models. CONCLUSIONS: Sterol carrier protein 2 may function as a moderator of HMGCR in human hepatocytes. Likely influences cholesterol metabolism and bile lithogenicity of human liver cells by regulating the expression of HMGCR and CYP7A1. PMID- 24226718 TI - The effects of chronic bile reflux on the gastric mucosa of rats. AB - BACKGROUND/AIMS: To establish a rat model mimicking human bile reflux for studying the pathological effects of chronic bile reflux. MATERIALS AND METHODS: The duodenum of Sprague-Dawley rats was transected below the opening of the common bile duct, and a gastrojejunostomy was performed at the greater curvature of the forestomach. After the rats demonstrated bile reflux for 1 year, we studied the pathological features of the glandular stomach and forestomach mucosa. We also studied the effect of bile reflux on gastrin expression in the glandular stomach mucosa by using immunohistochemistry. RESULTS: Chronic bile reflux caused significant hyperplasia and expansion of gastric glands in the glandular stomach. Dysplasia and cancer formation also developed, but the incidence was significantly lower than that reported in the literature. Intestinal metaplasia and ulceration in the glandular stomach were also rare. In the forestomach, the squamous epithelium showed significant hyperplasia and keratinization along with keratin pearls and keratocysts. Intestinal metaplasia was rare and no tumorigenesis was observed. Chronic bile reflux significantly increased gastrin expression in the glandular stomach mucosa. CONCLUSIONS: When simulating the physiological bile reflux pathway, chronic bile reflux caused hyperplasia and expansion of gastric glands in the glandular stomach and squamous epithelial hyperplasia and keratinization in the forestomach. PMID- 24226719 TI - Major predictors for difficult common bile duct stone. AB - BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography has become the standard treatment for common bile duct stones worldwide. However, there are only a few reports with small number of patients concerning the factors that contribute to the technical difficulty of endoscopic retrograde cholangiopancreatography in these patients. In this study we aimed to investigate these factors in a large group of patients. MATERIALS AND METHODS: All patients with a naiive papilla (n=1850) who underwent endoscopic retrograde cholangiopancreatography during a study period of 2 years were prospectively evaluated. Of these, 757 patients with common bile duct stones were included in the study. Following successful cannulation, patients who needed either more than one episode for stone extraction or mechanical lithotripsy, extracorporeal shock wave lithotripsy, or patients in whom stone extraction could not be achieved endoscopically and underwent surgery were regarded as having "difficult stones". Age, sex, laboratory parameters, endoscopic and cholangiographic findings were recorded in all patients. Predictive factors for difficult stones were investigated using univariate and multivariate analysis. RESULTS: The study group consisted of 432 women and 325 men with a mean age of 60+/-16 years (range, 4 96). Of the total 757 patients, 654 (86.4%) had easy and 103 (13.6%) had difficult stones. Endoscopic stone extraction was successful in 98.1% of patients. A stricture distal to the stone (OR: 8.248), smaller common bile duct/stone diameter ratio (OR: 0,348), stone diameter (OR: 1,187) stone impaction (OR: 1,117) and higher bilirubin levels (OR: 1,1) were found to be independent predictors of difficult stone extraction on multivariate analysis. CONCLUSION: Endoscopic retrograde cholangiopancreatography is a very effective method for the treatment of common bile duct stones. Presence of a stricture distal to the stone, smaller common bile duct/stone diameter ratio, stone diameter, impacted stone, and higher bilirubin levels are significant predictors of difficult stone. PMID- 24226720 TI - A study in four European countries to examine the importance of sensory attributes of oral nutritional supplements on preference and likelihood of compliance. AB - BACKGROUND/AIMS: A study designed to examine the importance of the sensory attributes of oral nutritional supplements on preference and likelihood of compliance. MATERIALS AND METHODS: Independent individuals >= 50 years not currently receiving oral nutritional supplements were recruited to a two-stage, single-blind, randomised, preference study, conducted in four European countries. Stage 1 consisted of a 5-day trial period during which two units of commonly prescribed oral nutritional supplements were administered, with a different oral nutritional supplements being consumed each day. In Stage 2, all participants consumed two units daily of one oral nutritional supplements for five days and two units daily of a second oral nutritional supplements for a further five days. Using standardised hedonic scales, participants reported their perceptions of each oral nutritional supplements for a range of sensory attributes, and estimated how many units of each oral nutritional supplements they could consume. RESULTS: One thousand seven hundred seventy one individuals completed the study. The overall opinion of each oral nutritional supplements was strongly correlated with taste (r=0.91; p<0,0001), while unit volume demonstrated a weak relationship (r =0,29; p<0,0001). One oral nutritional supplements (Reformulated Ensure Plus) was preferred overall, scoring significantly higher for taste (p<0,05) and oral sensation (p<0,05) than other oral nutritional supplements. CONCLUSIONS: This study contributes to the understanding of how sensory attributes, particularly taste and oral sensation, influence preference and compliance to oral nutritional supplements. PMID- 24226721 TI - Jejunal stricture in a premature infant: Is cytomegalovirus the causative pathogen or a superinfection? AB - Cytomegalovirus infection can cause gastrointestinal disease, especially in immunocompromised patients and premature infants. In the neonatal period, however, gastrointestinal involvement is infrequent. A case of cytomegalovirus enteritis and jejunal stricture in a preterm neonate is presented. The diagnosis was established after the histopathology of the surgical specimen demonstrated the presence of cytomegalovirus inclusion bodies. Every neonatal gastrointestinal cytomegalovirus infection case has been described in the literature as a necrotizing enterocolitis-like illness, but none of them clearly identifies whether cytomegalovirus was the pathogen responsible for causing necrotizing enterocolitis or whether cytomegalovirus occured as an infection during the course of necrotizing enterocolitis. PMID- 24226722 TI - A severe course of Cronkhite-Canada syndrome and the review of clinical features and therapy in 49 Chinese patients. AB - We describe a severe case of Cronkhite-Canada syndrome and review the clinical features and therapy in 49 Chinese patients. A 67-year-old man who underwent severe chronic diarrhea had typical clinical manifestations of hyperpigmentation, hair loss, and dystrophic changes in the fingernails. Although sufficient nutrition support and other therapies reported in the literature were provided, the patient died of systemic failure one year later. Cronkhite-Canada syndrome is characterized by generalized gastrointestinal polyps associated with hyperpigmentation, hair loss, and onycholysis. Anemia, positive stool occult blood, serum electrolyte disturbances, and low serum proteins are the main clinical features of patients with Cronkhite-Canada syndrome. Most patients were diagnosed by esophagogastroduodenoscopy and/or colonoscopy, and polyps were found in the entire alimentary tract, except the notable exception of the esophagus. The polyp-like samples of mucosa, hyperplasia, and adenoma were characterized by acute/chronic inflammation. Four cases were complicated with cancer. The treatment of Cronkhite-Canada syndrome includes symptomatic and support therapy, administration of corticosteroids, antibiotics and acid inhibitors, therapeutic endoscopy, and surgery. While the mortality rate was reported as 47.3% (9/19), some patients may live a long life with controlled symptoms. PMID- 24226723 TI - Multidetector computed tomography diagnosis of adenomyomatosis of the gallbladder. AB - The differentiation of gallbladder adenomyomatosis from gallbladder carcinoma is important as both conditions may present with thickening of the gallbladder wall or as a focal mass. Identification of Rokitansky-Aschoff sinuses is the key feature in making an accurate diagnosis of gallbladder adenomyomatosis on imaging studies. The diagnosis of gallbladder adenomyomatosis can be made with accurately by multidetector computed tomography when the presence of Rokitansky-Aschoff sinuses (small cystic spaces within the thickened gallbladder wall) are noted. Herein we present multidetector computed tomography findings of a 27-year-old patient with gallbladder adenomyomatosis. PMID- 24226724 TI - Endosonography and elastography in the diagnosis of esophageal tuberculosis. PMID- 24226725 TI - An unusual simultaneous occurence of gastric adenocarcinoma, leiomyoma and B-cell small lymphocytic lymphoma involving the perigastric lymph nodes and spleen. PMID- 24226726 TI - Acute gastric volvulus presenting with gastric outlet obstruction and upper gastrointestinal bleeding. PMID- 24226727 TI - Thrombocytopenia as a side effect of pantoprazole. PMID- 24226728 TI - Preventive approaches for intrafamilial H. pylori transmission as an efficient target strategy to decrease the prevalence of the infection in developing countries. PMID- 24226729 TI - Small bowel volvulus secondary to post appendectomy adhesion band. PMID- 24226730 TI - A duodenal mass and acute pancreatitis. PMID- 24226731 TI - Discrimination between closely related Triticeae species using genomic DNA as a probe. AB - Labelled total genomic DNA was used as a probe in combination with blocking DNA to discriminate between taxonomically closely related species in the genera Hordeum and Secale. Discrimination was possible both by Southern hybridization to size-fractionated restriction enzyme digests of genomic DNA and by in situ hybridization to chromosome preparations. To distinguish between two species (e.g. H. vulgare and H. bulbosum), genomic DNA from one species was used as the labelled probe, while unlabelled DNA from the other species was applied at a much higher concentration as a block. The blocking DNA presumably hybridized to sequences in common between the block and the labelled probe, and between the block and DNA sequences on the membrane or chromosomes in situ. If so, mainly species-specific sequences would remain as sites for probe hybridization. These species-specific sequences are dispersed and represent a substantial proportion of the genome (unlike many cloned, species-specific sequences). Consequently, rapid nonradioactive methods detected probe hybridization sites satisfactorily. The method was able to confirm the parentage of hybrid plants. It has potentially wide application in plant breeding for the detection of alien DNA transfer, and it can be easily adapted to many species. PMID- 24226732 TI - Genetic structure of Glycine canescens, a perennial relative of soybean. AB - Allozyme variation as detected by starch gel electrophoresis was used to assess the extent and spatial organization of genetic variation across the entire range of Glycine canescens sensu lato. Eleven enzyme systems were assayed in 116 accessions of this taxon and 102 alleles were detected at a total of 31 loci. Eighty-one percent of loci were polymorphic. Most of this variation occurred between and very little within accessions. Three major groupings were detected. These groupings (groups 1, 2, and 3) also differed with respect to mean seed size and their geographic distribution. A further ten accessions stood out from these distinct groups. These accessions were most closely related to group 3 but were variable among themselves. In general, they were collected from highly dissected terrain, often in the remote interior of the continent. A final group of 18 problematic accessions (group X), originally tentatively identified as G. canescens on morphological grounds, was shown to be isozymically distinct from this species and was reclassified as one form of the polytypic species G. clandestina. PMID- 24226733 TI - Somaclonal variation in high tannin sorghums. AB - Genetic variants were found among over 6,000 primary plants (R1) regenerated from embryogenic tissue cultures of eight high tannin sorghums [Sorghum bicolor (L.) Moench]. Field assessment of somaclonal variation has progressed to the R2 population, with over 48,000 R2 seedlings (27,000 plants) in 1,126 rows from 1,055 R1 plants. A total of 43 variant phenotypes was recovered, including several types of chlorophyll deficiencies, dwarfism, short culm, sterility, narrow leaf, and several previously unreported variants, such as ragged leaf, multibranched heads, and Hydra, a developmental variant which produces large numbers of panicles. Variation production greatly depends on parent genotype and appears to increase with increasing time in cultures. The toal average somaclonal variation rate (based per 100 R1 plants) and somaclonal variant frequency (based per 100 R2 plants) estimated in the tested population were 11.3 and 1.6, respectively. Chimerism was found in regenerants. The estimated size of the mutated sector carried by mutant regenerants ranged from the whole plant to less than 3% of a single head. The average proportion of mutated R1 heads carrying large (80%-100%), medium (40%-80%), and small (<40%) mutated sectors was 38.7%, 26.0% and 35.3%, respectively. Some sector mutations do not appear until the R3 generation. In order to avoid losing variants, the population for selecting somaclonal variation should be as large as possible. Some of these variants found may be useful for further study or for use in breeding programs. PMID- 24226734 TI - Intraspecific variation in nuclear DNA content among world populations of a mosquito, Aedes albopictus (Skuse). AB - Aedes albopictus is commonly distributed in most parts of the Oriental region and on many islands in the Indian and the Pacific Oceans. The species was recently introduced into the United States and Brazil. Feulgen cytophotometric quantitation of haploid nuclear DNA content was carried out for 37 populations of Ae. albopictus to determine the extent of intraspecific variation in nuclear DNA content and whether the range expansion of the species has coincided with an increase in DNA content. The haploid nuclear DNA content varied nearly three fold. The minimum DNA content was 0.62 pg in Koh Samui from Thailand, and the maximum DNA content was 1.66 pg in Houston-61 from the United States. Statistical comparisons of populations revealed significant differences in DNA contents. No geographic clustering of populations was noted with respect to DNA content. In general, populations from the United States and Brazil had higher DNA contents, but there was no indication that the range expansion had occurred hand in hand with an increase in DNA content. Each population had a specific amount of DNA that is probably imposed by the microenvironment. PMID- 24226735 TI - Imputing missing yield trial data. AB - The Additive Main effects and Multiplicative Interaction (AMMI) statistical model has been demonstrated effective for understanding genotype-environment interactions in yields, estimating yields more accurately, selecting superior genotypes more reliably, and allowing more flexible and efficient experimental designs. However, AMMI had required data for every genotype and environment combination or treatment; i.e., missing data were inadmissible. The present paper addresses the problem. The Expectation-Maximization (EM) algorithm is implemented for fitting AMMI depite missing data. This missing-data version of AMMI is here termed "EM-AMMI". EM-AMMI is used to quantify the direct and indirect information in a yield trial, providing theoretical insight into the gain in accuracy observed and into the process of imputing missing data. For a given treatment, the direct yield data are the replicates of that treatment, and the indirect data are all the other yield data in the trial. EM-AMMI is used to inpute missing data for a New York soybean yield trial. Important applications arise from both unintentional and intentional missing data. Empirical measurements demonstrate good predictive success, and statistical theory attributes this success to the Stein effect. PMID- 24226736 TI - DNA "fingerprints" applied to paternity analysis in apples (Malus x domestica). AB - Analysis of minisatellite DNA sequences, yielding so called DNA "fingerprints", has proven useful in paternity analysis for several different organisms. Here 64 apple seedlings, grown from seeds collected in an orchard with three cultivars, were analyzed using the M13 "fingerprint" probe. Paternity could be determined for 56 of the seedlings, 2 of which were derived through selfing. The analysis was facilitated by the occurrence of a multiallelic locus. The five different fragments determined by this locus migrated to similar positions, whether digesting the DNA with restriction enzymes TaqI or RsaI. PMID- 24226737 TI - Cytogenetic identification of Aegilops squarrosa chromosome additions in durum wheat. AB - A set of four normal chromosomes (1D, 2D, 3D, and 6D), and three translocation chromosomes (4DS.5DS, 5DL.7DS, and 7DL.4DL) involving all 14 chromosome arms of the D-genome were obtained as monosomic additions from Aegilops squarrosa (genome D, n=7) in Triticum durum Desf. cv 'PBW114' (genome AB, n=14). The cyclical translocation occurred during the synthesis of the amphiploid probably as a result of misdivision and reunion of the univalents during meiosis of the F1 hybrid T. durum x A. Squarrosa. The amphiploid was backcrossed twice with the durum parent to obtain monosomic addition lines. The monosomic addition chromosomes were identified by C-banding and associated phenotypic traits. All monosomic addition lines were fertile. The development of disomic and ditelosomic addition lines is underway, which will be useful for cytogenetic analysis of individual D-genome chromosomes in the background of T. Durum. PMID- 24226738 TI - An analytical model for the estimation of chromosome substitution effects in the offspring of individuals heterozygous at a segregating marker locus. AB - Use of marker genes for quantitative traits has been suggested as a supplement to selection for livestock species. Linkage relationships can be estimated by using data from offspring of a heterozygous parent, if offspring can be positively assigned segregation of one or the other of the marker alleles. In field data, some data on offspring can be characterized and used to estimate the difference in chromosome substitution effects, but other matings result in uncertain transfer of the marker alleles. In this study, an alternative estimation procedure is proposed that would allow incorporation of data on all offspring of a heterozygous parent, even those where chromosome segregation is ambiguous. If the frequency of the marker alleles is known in the population of mates of a heterozygous individual, the mean and variance of the heterozygous offspring can be used in a generalized leastsquares model to estimate the chromosome substitution effect. When gene frequencies are not known, maximum likelihood estimates can be obtained from the data for use in a conditional estimate. Monte Carlo simulations of data following the assumed genetic model were analyzed as proposed, and parameter estimates were characterized. Estimates of chromosome substitution effects were reasonable approximations of input values. Distributions of t-statistics testing the null hypothesis of no difference between marked chromosome segments were unbiased, with only slightly larger variance than expected. Addition of data from heterozygous offspring improved the efficiency of detection of chromosome substitution effects by more than four times when marker gene frequencies were low. PMID- 24226739 TI - Est-7, a set of genes controlling green tissue esterases in wheat and related species. AB - Analysis using isoelectric focusing of "Chinese Spring" wheat genetic stocks revealed a set of coleoptile and leaf esterase loci, designated Est-7, on the long arms of the group 2 chromosomes. A survey of 38 other hexaploid genotypes revealed onyl a single variant, at Est-D7. Homoeoloci were found on chromosome (arm) 2HL of Hordeum vulgare, 2RL of Secale cereale, 2R (m)alpha of S. montanum, 2U of Aegilops umbellulata, 2E of Agropyron elongation and 2V of Dasypyrum villosa. PMID- 24226740 TI - Characterization of soybean vegetative storage proteins and genes. AB - Soybean vegetative storage proteins (VSPs) were purified and characterized. Anion exchange HPLC resolved partially purified VSPs into fractions containing 27-kD/27 kD and 29-kD/29-kD homodimers and 27-kD/29-kD heterodimers. Reversed-phase HPLC resolved partially purified VSPs into three fractions. One fraction contained only 27-kD VSP and the other two contained 29-kD VSP. The two 29-kD VSP fractions differed with respect to their cyanogen bromide cleavage patterns, an observation that indicated the 29-kD VSPs were heterogeneous. Genomic clones that contained 29-kD VSP genes were also isolated and characterized. One genomic clone contained a complete 29-kD VSP gene and was sequenced. The coding region in the clone contained two introns whose borders had regulatory sequences typical of other eukaryotic genes. Putative polyadenlyation signals were present in the 3' flanking region of the gene, while putative TATA, CAAT, and enhancer core sequences were found in the 5'-flanking regions. A second genomic clone that was studied contained the 5' regions of two partial 29-kD VSP genes in an inverted linkage. Genomic DNA gel blots showed that the two genes were organized in the same arrangement in the soybean genome. PMID- 24226741 TI - Variation in the ribosomal DNA intergenic spacer of a maize population mass selected for high grain yield. AB - Variation in the intergenic spacer of ribosomal DNA (rDNA) was detected among individual plants of the open-pollinated maize variety 'Hays Golden' and populations derived from this variety. rDNA intergenic spacer-length variants were detected at approximately 200 bp intervals, consistent with the number of 200 bp subrepeats as the basis for this variation. Inheritance data revealed that more than one spacer-length class may be present on an individual chromosome. Fourteen different predominant rDNA intergenic spacer hybridization fragment patterns were detected. C-29, a population developed by 29 cycles of mass selecting Hay Golden for high grain yield, exhibited a significant change in rDNA intergenic spacer hybridization fragment pattern composition in comparison to Hays Golden. This change included a reduction in frequency of the shortest predominant space-length variant (3.4 kb) and an increase in a 5.2 -kb hybridization fragment. I-31, a population developed through thermal neutron irradiation of Hays Golden and 31 generations of mass selection for high grain yield, did not exhibit a significant change in overall rDNA intergenic spacer composition. I-31 did exhibit an increase in frequency of the 5.2-kb hybridization fragment and a significant change in two specific hybridization fragment patterns that had also changed in C-29. These data, particularly for the C-29 population, suggest that rDNA intergenic spacer-length variants and/or associated loci were influenced by selection. PMID- 24226742 TI - Abscisic acid deficiency prevents development of freezing tolerance in Arabidopsis thaliana (L.) Heynh. AB - Abscisic acid (ABA) has been implicated as a regulatory factor in plant cold acclimation. In the present work, the cold-acclimation properties of an ABA deficient mutant (aba) of Arabidopsis thaliana (L.) Heynh. were analyzed. The mutant had apparently lost its capability to cold acclimate: the freezing tolerance of the mutant was not increased by low temperature treatment but stayed at the level of the nonacclimated wild type. The mutational defect could be complemented by the addition of exogenous ABA to the growth medium, restoring freezing tolerance close to the wild-type level. This suggests that ABA might have a central regulatory function in the development of freezing tolerance in plants. Cold acclimation has been previously correlated to the induction of a specific set of proteins that have been suggested to have a role in freezing tolerance. However, these proteins were also induced in the aba mutant by low temperature treatment. PMID- 24226743 TI - Homologies to plastid DNA in the nuclear and mitochondrial genomes of potato. AB - Potato plastid DNA clones, representing onefourth of the potato plastome complexity and containing sequences of the 16SrRNA, rps16, atpA, atpE, psaA, psaB, trnK, trnV, and trnG genes, were used as hybridization probes on nuclear- and mitochondrial-enriched DNAs. Each probe hybridized to multiple nuclear restriction fragments distinct from the plastid cleavage products generated by the same endonucleases. The nuclear hybridizable fragments are highly methylated at their Hpall target sequences (C/CGG). In some instances, the transfer seemed to involve plastid regions of several kilobase pairs, as reflected by the co integration in the nucleus of restriction sites that are distant in the plastome. Three clones hybridized additionally to distinct mitochondrial fragments. These results indicate that extensive DNA transfers did occur between plastids and other organelles in potato. PMID- 24226744 TI - The agronomic performance of wheat doubled haploid lines derived from wheat x maize crosses. AB - The agronomic performance of 9 doubled haploid (DH) lines of Chinese Spring, 6 DH lines of Hope, 14 DH lines of the single chromosome substitution line Chinese Spring (Hope 5 A) and their respective parents was analyzed under field conditions. Seventeen Chinese Spring DH lines derived from wheat x Hordeum bulbosum crosses were also included for comparison. No significant variation was detected in either population of Chinese Spring DH lines and neither DH population differed from its parent. The Hope DH lines differed significantly for tiller biomass, spikelet number per ear, ear grain weight and 50-grain weight. However, all the variation could be attributed to the poor performance of only one line. Chinese Spring (Hope 5 A) DH lines showed significant variation for ear emergence time, but this was probably due to genetic heterogeneity in the parental stock. Overall, the results suggest that most DH lines produced by the wheat x maize method resemble their wheat parent, and that the variation induced in DH production is likely to be similar to that found in DHs from wheat x Hordeum bulbosum crosses. PMID- 24226745 TI - High-rate spontaneous reversion to cytoplasmic male sterility in sugar beet: a characterization of the mitochondrial genomes. AB - Among the fertile sugar beet lines with nuclear sterility maintenance genes, rf, in a homozygous recessive state, sublines capable of reverting spontaneously at a high rate to sterility were identified. Of 24 related fertile sublines studied, 6 were found to spontaneously revert to sterility with a frequency of about 19%. Genetic analysis confirmed the cytoplasmic nature of spontaneously arising sterility. Reversion to sterility in these sublines was accompanied by alterations in the mitochondrial genome structure: loss of the autonomously replicating minicircle c (1.3 kb) and changes in the restriction patterns of high molecular-weight mitochondrial DNA (mtDNA). Southern hybridixation analysis with cloned minicircle c as a probe revealed no integration of this DNA molecule into the main mitochondrial and nuclear genomes of the revertants. Comparative BamHI and EcoRI restriction analysis of the mtDNA from the sterile revertants and fertile parental subline showed that the spontaneous reversion is accompanied by extensive genomic rearrangement. Southern blot analysis with cloned alpha-subunit of F1-ATPase (atpA) and cytochrome c oxidase subunit II (COX II) genes as probes indicated that the changes in mtDNA accompanying spontaneous reversion to sterility involved these regions. The mitochondrial genomes of the spontaneous revertants and the sterile analogue were shown to be identical. PMID- 24226746 TI - Early-acting inbreeding depression and reproductive success in the highbush blueberry, Vaccinium corymbosum L. AB - Tetraploid Vaccinium corymbosum genotypes exhibit wide variability in seed set following self- and cross-pollinations. In this paper, a post-zygotic mechanism (seed abortion) under polygenic control is proposed as the basis for fertility differences in this species. A pollen chase experiment indicated that self-pollen tubes fertilize ovules, but are also 'outcompeted' by foreign male gametes in pollen mixtures. Matings among cultivars derived from a pedigree showed a linear decrease in seed number per fruit, and increase in seed abortion, with increasing relatedness among parents. Selfed (S1) progeny from self-fertile parents were largely self-sterile. At zygotic levels of inbreeding of F>0.3 there was little or no fertility, suggesting that an inbreeding threshold regulates reproductive success in V. corymbosum matings. Individuals below the threshold are facultative selfers, while those above it are obligate outcrossers. Inbreeding also caused a decrease in pollen viability, and reduced female fertility more rapidly than male fertility. These phenomena are discussed in terms of two models of genetic load: (1) mutational load - homozygosity for recessive embryolethal or sub-lethal mutations and (2) segregational load - loss of allelic interactions essential for embryonic vigor. Self-infertility in highbush blueberries is placed in the context of 'late-acting' self-incompatibility versus 'early-acting' inbreeding depression in angiosperms. PMID- 24226747 TI - Predicting cumulated response to directional selection in finite panmictic populations. AB - Accurate prediction of the cumulated genetic gain requires predicting genetic variance over time under the joint effects of selection and limited population size. An algorithm is proposed to quantify at each generation the effects of these factors on average coefficient of inbreeding, genetic variance, and genetic mean, under a purely additive polygenic model, with no mutation, and under the assumption of absence of inbreeding depression on viability affecting selection differentials. This algorithm is relevant to populations where mating is at random and generations do not overlap. It was tested via Monte Carlo simulation on a population of 3 males and 25 females mass selected out of 50 candidates of each sex, over 30 generations. For two values of the initial heritability of the selected trait, 0.5 and 0.9 (to represent high accuracy in index selection), predicted values of the genetic variance are in agreement with observed results up to the 12th and 19th generations, respectively. Beyond these generations, the variance is overestimated, due to an underestimation of the effect of selection on the rate of inbreeding. Finally, the algorithm provides predictions of the cumulated responses close to the observed values in both selected populations. It is concluded that, as regards the hypotheses of the study, the proposed algorithm is satisfactory, and could be used to optimize selection methods with respect to the cumulated genetic gain in the mid- or long-term. Possible extensions of the algorithm to more realistic situations are discussed. PMID- 24226748 TI - Genetic analysis of risk in clonal populations of forest trees. AB - A major concern arising from the culture of clonally propagated crops of forest trees is risk of catastrophic loss due to an agent or event not anticipated at the time of population establishment. Since danger of such a catastrophe depends to some degree on the genetic variability within clonal mixtures, attention has been focused on the number of clones needed to keep the risk of catastrophic loss below specified levels. In this paper, we describe a genetical analysis of susceptibility to a destructive agent and the effect that frequency of genes for susceptibility have on the number of clones needed to effectively manage this risk. As a part of the analysis, parameters representing the minimum unacceptable mortality rates in plantations (beta) and acceptable levels of risk (alpha) are defined, and their effects on the number of single-pair matings needed for the production of clonal stock are evaluated. Dominance and recessive gene action models for a single two-allele genetic locus are investigated. Probabilities for plantation failure are functions of the gene frequency for the allele conferring susceptibility. These functions converge to zero for allele frequencies less than beta but to one for frequencies greater than or equal to beta. This convergence is periodic rather than monotonie, since probabilities for plantation failure increase rather than decrease over restricted ranges of increasing numbers of clones. Recessive and dominance gene actions are found to have different effects on the minimum number of clones needed to attain acceptable risk levels. For conditions in which substantial numbers of clones are required, selecting multiple clones per mating is an effective method for reducing the number of matings necessary to achieve acceptable risks. PMID- 24226749 TI - Asymptotically efficient partial diallel crosses. AB - The asymptotic efficiency of partial diallel crosses is defined, and circulant plans having such a property are identified. In the absence of an optimal plan to suit his requirements, the breeder should opt for suggested plans to derive maximum information for given resources. PMID- 24226750 TI - The equivalence of two linear methods for the improvement of traits expressed as ratios. AB - Many traits of interest to animal breeders can be expressed as ratios. Yet there remains no uniquely agreed upon method for the genetic evaluation for ratio traits. To generalize, livestock breeders make direct use of ratios (e.g., feed/gain) or linear approximations to ratios. Dairy breeders, on the other hand, tend to use ratios of linear predictors of genetic merit for the evaluation of ratio traits (e.g., fat percent). In the present note, we demonstrate that the two methods are nearly, though not exactly, identical. The proof relies on the expression of the approximate correlation between two ratios. PMID- 24226751 TI - Biomolecular identification of ancient Mycobacterium tuberculosis complex DNA in human remains from Britain and continental Europe. AB - Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB. PMID- 24226752 TI - Elevated first trimester PAPP--a is associated with increased risk of placenta accreta. AB - OBJECTIVES: The objective of this article is to determine whether there were differences in first trimester serum analytes between cases of placenta previa with and without accreta. METHODS: Cases of placenta previa in which the patient had first trimester aneuploidy screening were identified. Pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fbhCG) MoMs were compared with those with an accreta. Accreta cases were also compared with published distributions to determine significance and to develop likelihood ratios based on MoM values. RESULTS: Eighty-two cases of previa were identified, including 16 with a histological diagnosis of placenta accreta. The median PAPP-A MoM of 1.68 in accreta was significantly greater than that of 0.98 in non-accreta (P = 0.002). For fbhCG, the median MoM was 1.00 and 1.01 in accreta and non accreta, respectively. Of the 16 patients with accreta, 14 (87.5%, 95% confidence interval: [61.6%, 98.4%]) had PAPP-A MoM above 1.0. Six of 16 (37.5%) accreta cases were above the 90th percentile of the unaffected distribution. The likelihood ratios for accreta were 0.5, 2.0, and 3.0. PAPP-A MoMs were 0.19, 2.11, and 4.27, respectively. CONCLUSIONS: First trimester PAPP-A levels may be useful in identifying pregnancies at high risk for placenta accreta. Larger studies could incorporate both clinical and biochemical data into a risk algorithm. PMID- 24226753 TI - Molecular characterisation and phylogenetic analysis of feline astrovirus in Korean cats. AB - Astroviruses (AstVs) are important pathogens associated with enteric diseases in humans and other animals. However, most animal AstVs, including feline astrovirus (FAstV), are poorly understood. The aim of the present study was to investigate the prevalence and association of FAstV with enteric diseases in cats, and to conduct a molecular analysis of FAstVs, in Korea. Eleven faecal samples from 62 hospitalised cats at animal hospitals in the Moran market in South Korea tested positive for FAstV. The prevalence of FAstV was higher in cats <2 months old (25%) than in cats >2 months old (14.3%) (P = 0.31). Diarrhoea and normal faeces were observed in 19% (8/42) and 15% (3/20) of cats with FAstV, respectively (P = 1.00). Amino acid sequences alignment and phylogenetic tree analysis showed that FAstVs, including Korean strains, formed a single clade within the mamastroviruses. PMID- 24226754 TI - Feline reference intervals for the Sysmex XT-2000iV and the ProCyte DX haematology analysers in EDTA and CTAD blood specimens. AB - Laser-based haematology analysers are routinely used in veterinary clinical pathology laboratories, and are available to practitioners. However, feline haematological reference intervals (RIs) determined according to international recommendations are, to our knowledge, not available. Furthermore, platelet count RI is difficult to establish in cats because of the frequent occurrence of platelet aggregation in blood specimens. The purpose of this study was to establish feline haematological RIs with the Sysmex XT-2000iV and ProCyte DX analysers, in ethylenediamine tetra-acetic acid (EDTA) and in citrate, theophylline, adenosine and dipyridamole (CTAD), which is a combination of anticoagulants limiting platelet aggregation. Blood specimens from 120 healthy cats were analysed in duplicate, and the degree of platelet aggregation was assessed on blood smears. After exclusion of inadequate specimens, 81 sets of results (from 44 males and 37 females, aged from 6 to 116 months) were available for the determination of RIs by the non-parametric method. The effects of the anticoagulant, analyser and aggregation score were assessed. When the aggregation effect was significant, the RIs were determined using the subgroup of blood specimens with no or little aggregation. The effects of sex, age and weight were also investigated, but were moderate. The different RIs obtained with the Sysmex XT-2000iV and ProCyte DX analysers, and the two anticoagulants, were very similar to previous RIs established in EDTA with the ADVIA 120, another laser-based analyser, except for the platelet count in CTAD specimens. Its lower reference limit was higher in CTAD vs EDTA specimens, which confirms the interest in this anticoagulant in cats. PMID- 24226755 TI - Prevalence of otitis externa in stray cats in northern Italy. AB - Feline otitis externa is a dermatological disorder that has not been evaluated much in stray cats. One hundred and eighty-seven stray cats were randomly selected during a trap-neuter-release programme to investigate the prevalence of otitis externa in stray cat colonies in northern Italy. Swabs for cytological examination were obtained from the external ear canal of each cat. A direct otoscopic assessment of the external ear canal was made in 86/187 cats. Cytological evidence of otitis externa was present in 55.1% of cats. The influence on otitis of age, gender, habitat and season of sampling was tested, but no risk factors were found. Otodectes cynotis (as a sole agent or in combination) was the primary cause of otitis in 53.3% of cats. Cocci and rods, either alone or in combination with other agents, were perpetuating factors in 71.8% and 29.1% of cats, respectively. Pregnancy status was a risk factor for otitis caused by coccal infections. Malassezia species, alone or in combination, was the perpetuating factor in 50.5% of cats with otitis. Urban habitat and winter season were risk factors for otitis associated with Malassezia species. Demodex cati was identified as an incidental finding in two cats. There was good agreement between otoscopy and cytology with regard to the diagnosis of otitis externa. The results of this study show a high prevalence of otitis externa in stray colony cats and provide information on causal factors for feline otitis externa. PMID- 24226756 TI - Addressing women's breast cancer risk and perceptions of control in medical settings. AB - Many women with family histories of breast cancer deal with two distinct but related issues: their objective physical risk and the emotions this risk engenders. Studies indicate that approximately 70% of African American and white women are concerned about their chances of developing breast cancer someday and perceive themselves to be at risk. Health care providers, including psychologists, need to be aware of the special needs and psychosocial concerns of high-risk women with family histories of breast cancer, since perceptions of breast cancer risk influence screening practices. Providers need training in understanding the significance of specific family patterns of breast cancer, screening guidelines appropriate for women at risk, and the benefits and risks of available prevention options, including genetic screening. Delivering accurate information about both established risk factors known to elevate personal risk, such as age and family history, and factors which women associate with breast cancer, such as bumping and bruising a breast, smoking, and oral contraceptive use, is essential for promoting accurate risk perceptions and appropriate screening schedules. PMID- 24226757 TI - Psychosocial correlates of eczema in a non-treatment-seeking population. AB - Data from the Vietnam Experience Study were used to examine psychosocial correlates of eczema. Based upon the results of dermatologic examinations, three groups of male veterans were identified: (a) subjects with eczema (n = 80), (b) subjects with tinea (n = 282), and (c) subjects with no medical diagnosis (n = 176). These three groups were compared on measures of anxiety, depression, hostility, and social support. The Diagnostic Interview Schedule (Version III-A) was used to determine diagnoses of anxiety and depression and level of social support. MMPI Scales 2 and 7, the Wiggins content scale of Depression, and the Cook-Medley Hostility Scale were used to assess anxiety, depression, and hostility. Eczema subjects did not differ from tinea or no-disease control groups on dependent measures. These results are contrasted with previous studies of treatment-seeking patients, which showed greater prevalence of anxiety and depression among individuals with eczema. Directions for future research are suggested. PMID- 24226758 TI - Interaction of asthmatics and their spouses: A preliminary study of individual differences. AB - Some asthmatics show evidence of airways reactivity triggered by strong emotions. Six case studies of married patients with severe asthma are reported. The videotaped interactions of the asthmatic and his/her spouse were coded for affect and behavior. Repeated measures of pulmonary function and affective state were recorded before and after two interaction tasks. Over the course of the experimental period, two patients' pulmonary function improved and four patients' deteriorated. In general, decreased pulmonary function was associated with more self-rated hostility and depression. The results are discussed in terms of their implications for the intra- and interpersonal factors that are important in asthma management. PMID- 24226759 TI - Personality disorders and response to outpatient treatment of chronic pain. AB - As part of a comprehensive interdisciplinary evaluation conducted prior to participation in an outpatient chronic pain treatment program, the psychological status of 101 persons was assessed. The majority of participants was found to have a form of personality disorder, determined by conservative cutoff scores applied to their Millon Clinical Multiaxial Inventory (MCMI) profiles. DSM-III-R Cluster C disorders (i.e., Avoidant, Dependent, Obsessive-Compulsive, and Passive Aggressive) were overrepresented in this sample. Subsequent analyses revealed that personality disorders were related to higher levels of self-reported distress and pain at both the beginning and the end of outpatient treatment. Differential responses to treatment were observed on self-report measures; however, few relations were found between personality disorder and physical therapist ratings of impairment and improvement. Implications for the assessment of personality disorders in outpatient pain treatment programs are discussed and appropriate intervention strategies are considered. PMID- 24226760 TI - Developmental changes of parental-reported sleep disturbance symptoms in children with attention deficit disorder. AB - The primary goal of this retrospective study was to assess parental report of current sleep disorders in school-aged attention deficit disorder (ADD) children, as well as recalled sleep problems from when the children were infants (0-12 months) and toddlers (1-3 years). Results of a sleep questionnaire completed by mothers of 48 ADD children and a comparison group of 30 patients with school problems indicate that ADD children were perceived to have significantly more sleep problems and that these problems had onset in infancy. Specific items in the questionnaire which were increased included latency to sleep onset of more than 30 min at least 3 nights per week, fatigue upon awakening, and recall of nightmares. Pediatric clinicians should be alert to possible sleep disorders in children suspected of attention disorders and should consider "sleep hygiene" measures as a component of treatment. PMID- 24226761 TI - Prevalence of traumatic brain injury in an inpatient psychiatric population. AB - This study investigated the prevalence of traumatic brain injury (TBI) in an inpatient psychiatric population. We hypothesized increased prevalence of TBI relative to the general population due to a variety of risk factors observed in psychiatric patients. One hundred (mean age = 34) psychiatric inpatients completed the revised Head Injury Questionnaire. Chart review of 17 subjects reporting injuries established whether injuries were documented in medical records. Sixty-eight percent of this psychiatric population reported one or more injuries in which they were unconscious or dazed. This number is higher than the prevalence in the general population. Injuries were generally of mild to moderate severity; multiple injuries were common. Chart review of 17 subjects reporting TBI indicated that histories of TBI had not been noted in the medical record. Finally, 63% of TBI subjects reported that their injury predated the onset of their psychiatric symptoms. These results suggest a possible role of TBI in psychiatric symptomatology and have implications for psychiatric treatment in this population. PMID- 24226762 TI - Psychological aspects of scuba diving injuries: Suggestions for short-term treatment from a psychodynamic perspective. AB - Dive medicine is described as an area of practice in which psychologists may choose to expand their clinical service and research activities. The author argues that most research studying risk behavior and sports take into account biological, behavioral or cognitive approaches, while ignoring unconscious conflict in risk-taking and injury management. The present paper uses a psychodynamically-oriented, interview-based approach to studying psychological reactions to decompression sickness in three experienced scuba divers. Brief interventions and their outcomes are described. PMID- 24226763 TI - Methods for overcoming methodological problems in the measurement of client satisfaction in a clinical psychology practice. AB - This study surveyed client satisfaction with an outpatient service in clinical psychology at a university-based clinic in New Zealand. In an effort to collect honest opinions rather than "grateful testimonials" from clients, special consideration was given to the methodology used. In the absence of guidelines on how to analyze client satisfaction data, a variety of techniques was developed. These methods and analyses are reviewed and recommendations made with regard to future use. PMID- 24226764 TI - Long-term prognosis of metacarpal and metatarsal fractures in dogs. A retrospective analysis of medical histories in 100 re-evaluated patients. AB - OBJECTIVES: Lameness after metacarpal and metatarsal fractures in dogs is reported to occur with an incidence of 18% to 70%. On the basis of long-term results, the prognosis of these injuries was re-evaluated retrospectively. METHODS: Medical records of 100 dogs with complete clinical and radiographic follow-up examinations after an average of four years (4 months - 14 years) were evaluated. According to their treatment, patients were allocated to three groups (Group 1=conservative, Group 2=surgical, Group 3=combined). Assessment included complications during the healing period and the final radiographic and functional outcome, which was statistically compared for differences between groups (Fisher exact test, exact Wilcoxon-Mann-Whitney test). Further, risk factors for each bone were analyzed (stepwise, multiple logistic regression model). In 15 dogs, kinetic data (relative stance phase, peak vertical force and impulse) were investigated by computed gait analysis. RESULTS: Complications were observed in 11 of 67 (16%) conservatively, in three of 25 (12%) surgically, and in three of eight (37%) conservatively and surgically treated dogs. Overall frequency of lameness evaluated by visual clinical assessment was three percent. Frequency of osteoarthritis and nonunion was also low, accounting for three percent and one percent respectively, although healing of mainly single-bone fractures resulted in malunions in 14% radiographically. Synostoses were found in 19% of patients, and significantly more frequent in surgically treated dogs. A higher risk of complications was identified for metatarsal compared to metacarpal fractures. Further, an increased risk for complications was detected for a higher degree of displacement and instability. CLINICAL SIGNIFICANCE: According to the long-term results found in this study, the prognosis for metacarpal and metatarsal fractures is better than reported in the literature to date. With the reservation that more severe injuries are generally treated surgically, and these fractures more frequently developed synostosis, no significant difference could be detected between conservative and surgical treatment. PMID- 24226765 TI - Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study. AB - There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. PMID- 24226766 TI - Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing. AB - miRNAs are generally classified as "intergenic" or "intronic" based upon their genomic location. Intergenic miRNAs are known to be transcribed as independent transcription units, while intronic miRNAs are believed to be processed from the introns of their hosting transcription units and hence share common regulatory mechanisms and expression patterns with its host gene. Recent reports in the literature suggest that some intronic miRNAs, which do not show concordance in expression with their respective host genes, might be transcribed and regulated as independent transcription units. However, there is no direct evidence for the existence of independently transcribed intronic miRNA in humans to date. We have characterized the full-length primary transcripts (pri-miRNAs) of three human intronic miRNAs-miR 106b, miR 93, and miR 24-1-by RNA ligase-mediated RACE and show that human intronic miRNA can indeed be transcribed as independent transcription units. Also, clustered miRNAs are generally believed to arise from a common primary transcript and are expected to have similar expression profiles. However, we have identified several novel alternatively spliced transcripts by RT PCR, each of which harbors a single pre-miRNA from a cluster of closely located intronic miRNAs. We show that these transcripts represent unique pri-miRNAs for each of these clustered miRNAs. We also report the identification of conserved splice acceptor signals which are responsible for maturation of these novel splice variants. Our results suggest that alternative splicing might play a role in uncoupling the expression of clustered miRNAs from each other, which otherwise are generally believed to be co-transcribed and co-expressed. PMID- 24226767 TI - Themis sets the signal threshold for positive and negative selection in T-cell development. AB - Development of a self-tolerant T-cell receptor (TCR) repertoire with the potential to recognize the universe of infectious agents depends on proper regulation of TCR signalling. The repertoire is whittled down during T-cell development in the thymus by the ability of quasi-randomly generated TCRs to interact with self-peptides presented by major histocompatibility complex (MHC) proteins. Low-affinity TCR interactions with self-MHC proteins generate weak signals that initiate 'positive selection', causing maturation of CD4- or CD8alphabeta-expressing 'single-positive' thymocytes from CD4(+)CD8alphabeta(+) 'double-positive' precursors. These develop into mature naive T cells of the secondary lymphoid organs. TCR interaction with high-affinity agonist self ligands results in 'negative selection' by activation-induced apoptosis or 'agonist selection' of functionally differentiated self-antigen-experienced T cells. Here we show that positive selection is enabled by the ability of the T cell-specific protein Themis to specifically attenuate TCR signal strength via SHP1 recruitment and activation in response to low- but not high-affinity TCR engagement. Themis acts as an analog-to-digital converter translating graded TCR affinity into clear-cut selection outcome. By dampening mild TCR signals Themis increases the affinity threshold for activation, enabling positive selection of T cells with a naive phenotype in response to low-affinity self-antigens. PMID- 24226768 TI - Antibiotics: Killing the survivors. PMID- 24226769 TI - The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. AB - Heterotaxy is a disorder of left-right body patterning, or laterality, that is associated with major congenital heart disease. The aetiology and mechanisms underlying most cases of human heterotaxy are poorly understood. In vertebrates, laterality is initiated at the embryonic left-right organizer, where motile cilia generate leftward flow that is detected by immotile sensory cilia, which transduce flow into downstream asymmetric signals. The mechanism that specifies these two cilia types remains unknown. Here we show that the N acetylgalactosamine-type O-glycosylation enzyme GALNT11 is crucial to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking the ciliopathy primary ciliary dyskinesia. Together our data demonstrate that Galnt11 modifies Notch, establishing an essential balance between motile and immotile cilia at the left right organizer to determine laterality, and reveal a novel mechanism for human heterotaxy. PMID- 24226771 TI - Human evolution: Group size determines cultural complexity. PMID- 24226770 TI - Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. AB - Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host microbe interactions establish immunological homeostasis in the gut. PMID- 24226772 TI - Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. AB - Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic beta-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus. PMID- 24226774 TI - Baryons in the relativistic jets of the stellar-mass black-hole candidate 4U 1630 47. AB - Accreting black holes are known to power relativistic jets, both in stellar-mass binary systems and at the centres of galaxies. The power carried away by the jets, and, hence, the feedback they provide to their surroundings, depends strongly on their composition. Jets containing a baryonic component should carry significantly more energy than electron-positron jets. Energetic considerations and circular-polarization measurements have provided conflicting circumstantial evidence for the presence or absence of baryons in jets, and the only system in which they have been unequivocally detected is the peculiar X-ray binary SS 433 (refs 4, 5). Here we report the detection of Doppler-shifted X-ray emission lines from a more typical black-hole candidate X-ray binary, 4U 1630-47, coincident with the reappearance of radio emission from the jets of the source. We argue that these lines arise from baryonic matter in a jet travelling at approximately two-thirds the speed of light, thereby establishing the presence of baryons in the jet. Such baryonic jets are more likely to be powered by the accretion disk than by the spin of the black hole, and if the baryons can be accelerated to relativistic speeds, the jets should be strong sources of gamma-rays and neutrino emission. PMID- 24226773 TI - Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. AB - Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms. PMID- 24226775 TI - Experimental evidence for the influence of group size on cultural complexity. AB - The remarkable ecological and demographic success of humanity is largely attributed to our capacity for cumulative culture. The accumulation of beneficial cultural innovations across generations is puzzling because transmission events are generally imperfect, although there is large variance in fidelity. Events of perfect cultural transmission and innovations should be more frequent in a large population. As a consequence, a large population size may be a prerequisite for the evolution of cultural complexity, although anthropological studies have produced mixed results and empirical evidence is lacking. Here we use a dual-task computer game to show that cultural evolution strongly depends on population size, as players in larger groups maintained higher cultural complexity. We found that when group size increases, cultural knowledge is less deteriorated, improvements to existing cultural traits are more frequent, and cultural trait diversity is maintained more often. Our results demonstrate how changes in group size can generate both adaptive cultural evolution and maladaptive losses of culturally acquired skills. As humans live in habitats for which they are ill suited without specific cultural adaptations, it suggests that, in our evolutionary past, group-size reduction may have exposed human societies to significant risks, including societal collapse. PMID- 24226777 TI - Exposure to seawater stimulates lipid mobilization from depot tissues of juvenile coho (Oncorhynchus kisutch) and chinook (O. tshawytscha) salmon. AB - Tissue lipid content and lipolytic enzyme activity was determined in selected tissues of coho salmon,Oncorhynchus kisutch, at various developmental stages (freshwater parr, freshwater smolt, seawater smolt, and seawater stunt) and in tissues of coho salmon and chinook salmon,O. tshawytscha, exposed to seawater periodically during smoltification. Among developmental groups, total lipid concentration of liver and dark muscle was highest in freshwater (FW) parr. Lipid concentration in both liver and dark muscle was significantly lower in FW smolts, seawater (SW) smolts and SW stunts; no difference was observed among these groups. Alterations in lipid composition were reflected in depot triacylglycerol lipase activity. FW smolts, SW smolts and SW stunts displayed significantly higher lipase activity than FW parr in each of the tissues examined (live, dark muscle and mesenteric fat). Early in smoltification (March, April), exposure to seawater results in enhanced lipid depletion from liver, dark muscle and mesenteric fat, both 30 and 60 days after exposure, compared to FW controls. This depletion was accompanied by increased liver (March and April) dark muscle (March) and mesenteric fat (March) lipase activity. Later in smoltification (May), salinity-induced alterations in lipid metabolism were not observed. These results indicate that exposure to seawater stimulates lipid depletion in juvenile salmon and that the depletion can be explained, in part, by increased depot lipase activity. Furthermore, these data confirm that metabolic dysfunction is associated with stunting. PMID- 24226778 TI - Transepithelial ion exchange in smolting atlantic salmon (Salmo Salar L.). AB - Whole-body (but predominantly gill) Na(+) exchange, gill Na(+)/K(+)/ATPase activity and seawater tolerance were examined in juvenile Atlantic salmon during the smolting period. Transepithelial net Na(+) gain decreased steadily from late February showing a net loss in April and early May, returning to approximate equilibrium in mid-May. This seasonal net loss of Na(+) to the environment occurred slightly after maximal gill epithelial Na(+)/K(+)/ATPase activity and preceded maximal seawater tolerance. The results are discussed in relation to changes in gill permeability and salt intake via the diet. PMID- 24226776 TI - Activated ClpP kills persisters and eradicates a chronic biofilm infection. AB - Chronic infections are difficult to treat with antibiotics but are caused primarily by drug-sensitive pathogens. Dormant persister cells that are tolerant to killing by antibiotics are responsible for this apparent paradox. Persisters are phenotypic variants of normal cells and pathways leading to dormancy are redundant, making it challenging to develop anti-persister compounds. Biofilms shield persisters from the immune system, suggesting that an antibiotic for treating a chronic infection should be able to eradicate the infection on its own. We reasoned that a compound capable of corrupting a target in dormant cells will kill persisters. The acyldepsipeptide antibiotic (ADEP4) has been shown to activate the ClpP protease, resulting in death of growing cells. Here we show that ADEP4-activated ClpP becomes a fairly nonspecific protease and kills persisters by degrading over 400 proteins, forcing cells to self-digest. Null mutants of clpP arise with high probability, but combining ADEP4 with rifampicin produced complete eradication of Staphylococcus aureus biofilms in vitro and in a mouse model of a chronic infection. Our findings indicate a general principle for killing dormant cells-activation and corruption of a target, rather than conventional inhibition. Eradication of a biofilm in an animal model by activating a protease suggests a realistic path towards developing therapies to treat chronic infections. PMID- 24226779 TI - Diurnal variations in hypothalamic monoamine levels in the teleostChanna punctatus (bloch) in response to melatonin under two photothermal conditions. AB - Hypothalamic dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) levels exhibited marked day-night variations under ambient photoperiod and temperature (12L?12D; 17+/-1 degrees C) with peak values at mid-light phase. The 16L?8D; 22+/-1 degrees C treatment reversed the diurnal rhythm of 5-HT, but not that of DA and NA. However, there was an overall increase in the levels of the catecholamines on exposure to the long photoperiod and high temperature. The administration of melatonin in the fish held on 16L?8D; 22+/-1 degrees C regime restored the 5-HT rhythm to that of the 12L?12D; 17+/-1 degrees C control group, but with elevated mid-photophase value. However, there was no effect of the indole treatment on the 5-HT rhythm under the 12L?12D; 17+/-1 degrees C regime. Melatonin causes a significant reduction of NA level in both the groups, while DA level did not change in either group. PMID- 24226780 TI - Effects of diet and feeding time on daily variations in plasma insulin, hepatic c AMP and other metabolites in a teleost fish,Dicentrarchus labrax L. AB - Juvenile sea bass, 1.5 years old, of mixed sex, held on long photoperiods were fed early on the photoperiod and late on the photoperiod, using different diets. Fish fed natural diets showed a daily rhythmicity of plasma insulin, liver c-AMP, plasma glucose, liver glycogen and muscle glycogen content, however, fish fed a commercial diet did not show this daily rhythmicity except for plasma insulin levels. In addition, these fish had significantly lower levels of plasma insulin, liver c-AMP and plasma glycerol than the group fed on the natural diets at similar feeding times. The time of feeding also induced different rhythmicity patterns in hormones and metabolites as well as a significant change in their mean levels. These facts are discussed in relation with the pre-feeding activity and increased appetite exhibited by the fish fed late on the photoperiod and with their implications on fish culture. PMID- 24226781 TI - Thyroidal compensation in rainbow trout (Salmo gairdneri) fed canola meal. AB - Rainbow trout (Salmo gairdneri Richardson) were fed either a soybean mealbased (SM) or canola meal-based (CM) diet for up to 20 weeks. Plasma thyroxine (T4) and triiodothryonine (T3) levels were significantly lower in the CM-fed fish sampled after 12 weeks. However, there appeared to be some compensation after 12 and 20 weeks in that the thyroid hormone levels in trout fed the CM were not significantly different from those of the SM-fed fish. Nevertheless, there was marked thyroid hyperplasia and hypertrophy in the CM-fed fish sampled at 12, 16 and 20 weeks after commencement of the experiment. Moreover, the growth rate was significantly lower in the CM-fed fish in comparison to the SM-fed fish throughout the 20 week study period.Plasma T4 levels were similar in SM-fed fish sampled 12, 16 and 20 weeks after commencement of the experiment, but plasma T3 levels progressively increased over this period, as did the apparent activity of the thyroid tissue based on histological criteria.Fasting for up to 8 weeks resulted in the arrested growth of the SM-fed fish, and a loss in body weight of the CM-fed animals over the 8 week period of the fast. In addition, the plasma thyroid hormone levels in the fasted fish tended to be lower than in fish fed both the SM and CM diets prior to fasting, and there was histological evidence indicating a reduced activity of the pituitary-thyroid axis. However, thyroid hyperplasia and hypertrophy were still evident in the fasted fish previously fed the CM diet indicating that the adverse affects of CM diets are not completely reversible after 8 weeks.In fish fed the CM diet for 12 weeks and then the SM diet for up to a further 8 weeks (diet C-S) there was a compensatory increase in plasma thyroid hormone levels evident within 4 weeks after the change in diet, but no apparent decrease in thyroid hyperplasia or hypertrophy. In addition, in the fish fed the C-S diet there was a marked compensatory growth rate, and an increased feed: gain ratio; body weights of this group of fish were not significantly different from those of the SM-fed animals after 20 weeks of study, indicating a considerably higher growth rate over the last 8 week period. PMID- 24226782 TI - Gonadotropic hormone (GtH) receptors in the testis of the troutSalmo gairdneri: in vitro studies. AB - A particulate fraction obtained from trout testis at the time of spermiation shows saturable binding sites for(125)I-labeled salmon gonadotropin ((125)I-GtH). Non-gonadal tissues (liver, muscle and spleen) did not demonstrate specific(125)I GtH binding. The tracer's specific activity was determined by the self displacement method (18 to 30 MUCi/MUg). Maximal specific binding ability of(125)I-GtH varied from 20 to 30% of the labelled ligand added, depending on the hormone preparation. Specific binding of(125)I-GtH to 20 mg of the testis membrane varied from 40 to 85% of the total binding depending on the method of membrane prepratation, and was competitively inhibited by concentrations of unlabelled GtH ranging from ca 1 to 1000 ng/ml of incubate. Gonadotropin of mammalian origin, ovine TSH or salmon prolactin competed only weakly, or not at all, for testicular gonadotropin binding sites (relative potencies s GtH>>FSH=hCG>s-PRL>bTSH). Scatchard analysis of equilibrium binding studies shows that saturable gonadotropin binding was due to a class of high affinity binding sites (sites I Ka?3*10(10) M(-1)) and possibly to a second class of lower affinity binding sites (sites II Ka=5 to 14*10(8) M(-1)). The binding capacity of sites I, as measured in enriched membrane preparations, was 45+/-18 fmoles/g of testis during the period of spermiation. The concentration of GtH required to obtain half maximal displacement of(125)I-GtH in the binding studies was of the same order of magnitude as the apparent ED50 for GtH stimulation of 11 Cetotestosterone (11KT) secretion by trout testesin vitro. Mammalian LH and FSH were 100 to 1000 folds less potent than salmor GtH to increase 11 KT secretion. PMID- 24226783 TI - The fatty acid compositions of established fish cell lines after long-term culture in mammalian sera. AB - The effect of long-term culture of fish cells in mammalian serum on the phospholipid fatty acid composition was investigated. All the cell lines studied had much lower levels of polyunsaturated fatty acids (PUFA) than those found in intact fish tissues. In particular (n-3) PUFA were considerably depleted in the cultured cell lines, leading to very low (n-3)/(n-6) ratios in all the phospholipid classes. In general the cells were rich in 18:1, 16:0, 18:0 and 16:1 with 20:4(n-6) and 22:6(n-3) as the major PUFA. The fatty acid composition reflected the composition of the fetal calf serum added to the media rather than their fish tissue origins. The results were discussed in relation to the roles of PUFA in general cell metabolism and more specifically the role of (n-3) PUFA in fish cells. PMID- 24226784 TI - Fatty acid compositions of the major phosphoglycerides from fish neural tissues; (n-3) and (n-6) polyunsaturated fatty acids in rainbow trout (Salmo gairdneri) and cod (Gadus morhua) brains and retinas. AB - The fatty acid compositions of brain phosphoglycerides from a freshwater fish, the rainbow trout (Salmo gairdneri), and a marine fish, the cod (Gadus morhua), were determined and compared with those from a terrestrial mammal, the rat. Fish brain lipids were characterized by a higher degree of unsaturation encompassing increased percentages of (n-3)PUFA (22?6 and 20?5) and lower percentages of (n 6)PUFA (20?4 and 22?4). However the distribution of fatty acids and specific PUFA between different phosphoglycerides was essentially similar in rat and fish brain tissue. PE and PS contained the highest percentages of 22?6(n-3), PI was characterized by higher 18?0 and 20?4(n-6)/20?5(n-3), and PC had higher 16?0 and the lowest percentage of PUFA in all species. A generally similar pattern was found in the fish retinal phosphoglycerides except that PC was also rich in 22?6(n-3). Overall trout brain phosphoglycerides were slightly more unsaturated than the cod lipids but with lower (n-3)/(n-6) ratios whereas cod retinal lipids were more unsaturated than the trout retinal lipids. PMID- 24226785 TI - Mitochondrial NAD(P)-malic enzyme from herring skeletal muscle : Purification and some kinetic and regulatory properties. AB - Mitochondrial NAD(P)-dependent malic enzyme [EC 1.1.1.39, L-malate: NAD(+) oxidoreductase (decarboxylating)] was purified from herring skeletal muscle to a specific activity of 8.2 MUmol/min/mg. The purification procedure involved chromatography on DEAE-cellulose, Red Agarose and a Sephacryl S-300 with a final recovery of 38% of enzyme activity. This enzyme catalyzes the oxidative decarboxylation of malate in the presence of either NAD or NADP in the presence of Mn(2+). Some kinetic characteristics of this enzyme were determined. The pH optimum of activity is 7.0. ATP was shown to be a competitive inhibitor with malate. The inhibition by ATP displayed hyperbolic competitive kinetics with a Ki (ATP) of 0.28 mM in the presence of NAD and 0.75 mM in the presence of NADP. Fumarate reversed ATP inhibition.In vivo, regulation of NAD(P)-dependent malic enzyme might respond to changing levels of mitochondrial ATP and fumarate with the enzyme undergoing kinetic activation by an increase in the concentration of mitochondrial fumarate which could reverse enzyme inhibition by ATP. PMID- 24226786 TI - Respiratory stress in rainbow trout dying from aluminium exposure in soft, acid water, with or without added sodium chloride. AB - Rainbow trout exposed to 32 MUM aluminium at pH=5.0 in artificial soft water ([Ca(++)]=50 MUM), with or without added sodium chloride (150 mM), suffer from severe respiratory stress characterized by hyperventilation, low PaO 2, high PaCO 2, low pHa and high blood lactate concentrations at death. Plasma chloride concentration at death had decreased in the group with no added NaCl, but not in the presence of added NaCl. Median survival times were not significantly different in the two groups. These findings suggest that death under the given conditions is primarily due to impeded gas exchange. PMID- 24226787 TI - Influence of pH and temperature on force development and shortening velocity in skinned muscle fibres from fish. AB - Three species of fish were studied: Atlantic cod (Gadus morhua), sculpin (Myoxocephalus scorpius) (from the North Sea, temperature 2 to 12 degrees C) andNotothenia neglecta (from Antarctica, temperature -2 to +2 degrees C). Single fast muscle fibres were isolated from anterior myotomes and skinned with detergent in order to directly determine the effects of pH and temperature on force production and shortening velocity.In all species maximum force production (Po) was independent of pH over the range 7.3-8.0. Decreasing the pH from 7.3 to 6.6 reduced maximum force by 28% in fibres fromG. morhua andN. neglecta but had no effect on fibres fromM. scorpius. The depression in maximum force with acidosis was accompanied by a proportional decrease in stiffness and an increase in the rate of force recovery after stretch.Unloaded contraction velocity of cod fibres (Vmax) showed a pH optimum at around pH 7.6 decreasing by 31% at pH 6.6. Vmax of fibres from the other species was independent of pH over the range 6.6 8.0.The effects of pH on Po and Vmax were similar at 0 and 10 degrees C. Thus for maximally activated fibres both force and contraction velocity are independent of temperature induced changes in pH. In some species acidosis depresses contractility and is likely to be a contributory factor to muscle fatigue. PMID- 24226788 TI - Recurrent melanocytic nevi and melanomas in dermoscopy: results of a multicenter study of the International Dermoscopy Society. AB - IMPORTANCE Differentiating recurrent nevi from recurrent melanoma is challenging. OBJECTIVE To determine dermoscopic features to differentiate recurrent nevi from melanomas. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of 15 pigmented lesion clinics from 12 countries; 98 recurrent nevi (61.3%) and 62 recurrent melanomas (38.8%) were collected from January to December 2011. MAIN OUTCOMES AND MEASURES Scoring the dermoscopic features, patterns, and colors in correlation with the histopathologic findings. RESULTS In univariate analysis, radial lines, symmetry, and centrifugal growth pattern were significantly more common dermoscopically in recurrent nevi; in contrast, circles, especially if on the head and neck area, eccentric hyperpigmentation at the periphery, a chaotic and noncontinuous growth pattern, and pigmentation beyond the scar's edge were significantly more common in recurrent melanomas. Patients with recurrent melanomas were significantly older than patients with recurrent nevi (mean [SD] age, 63.1 [17.5] years vs 30.2 [12.4] years) (P<.001), and there was a significantly longer time interval between the first procedure and the second treatment (median time interval, 25 vs 8 months) (P<.001). In a multivariate analysis, pigmentation beyond the scar's edge (P=.002), age (P<.001), and anatomic site (P=.002) were significantly and independently associated with the diagnosis of recurrent melanoma in dermoscopy. CONCLUSIONS AND RELEVANCE Dermoscopically, pigmentation beyond the scar's edge is the strongest clue for melanoma. Dermoscopy is helpful in evaluating recurrent lesions, but final interpretation requires taking into account the patient age, anatomic site, time to recurrence, growth pattern, and, if available, the histopathologic findings of the first excision. PMID- 24226789 TI - Endovascular management of venous ulcer in a patient with occluded duplicated inferior vena cava and review of inferior vena cava development. AB - Duplication of inferior vena cava (IVC) is the most common IVC anomaly. We report a successful iliac vein and collateral stenting for venous decompression in a patient with an occluded right femorocaval graft with a duplicated IVC. We also review the literature of embryological development of IVC. PMID- 24226790 TI - Inflammatory abdominal aortic aneurysm: a case report and review of literature. AB - We report a case of an abdominal aortic aneurysm (AAA) that underwent inflammatory transformation which we treated medically with corticosteroids. Medical therapy resulted in resolution of presenting symptoms and observed inflammatory changes. We review the clinical features, associated pathology, diagnostic, and therapeutic options in the management of inflammatory AAA. PMID- 24226791 TI - Wavelength-selective fluorescence as a novel tool to study organization and dynamics in complex biological systems. AB - The dynamics exhibited by a given component of a large macromolecule such as a folded globular protein or an organized supramolecular assembly like the biological membrane is a function of its precise localization within the larger system. A set of approaches based on the red edge effect in fluorescence spectroscopy, which can be used to monitordirectly the environment and dynamics around a fluorophore in a complex biological system, is reviewed in this article. A shift in the wavelength of maximum fluorescence emission toward higher wavelengths, caused by a shift in the excitation wavelength toward the red edge of the absorption band, is termed the red edge excitation shift (REES). This effect is mostly observed with polar fluorophores in motionally restricted media such as very viscous solutions or condensed phases. This phenomenon arises from the slow rates of solvent relaxation around an excited-state fluorophore, which is a function of the motional restriction imposed on the solvent molecules in the immediate vicinity of the fluorophore. Utilizing this approach, it becomes possible to probe the mobility parameters of the environment itself (which is represented by the relaxing solvent molecules) using the fluorophore merely as a reporter group. Further, since the ubiquitous solvent for biological systems is water, the information obtained in such cases will come from the otherwise 'optically silent' water molecules. This makes REES and related techniques extremely useful in biology since hydration plays a crucial modulatory role in a large number of important cellular events. PMID- 24226792 TI - New fluorescent dyes in the red region for biodiagnostics. AB - The increased sensitivity together with the advent of low-cost optical sources and detectors in the visible-near IR region has led us to current efforts to develop new efficient fluorescent labels for biodiagnostics with absorption and emission beyond 600 nm. In view of the general fluorescence decrease with increasing emission wavelength, we investigated the possibility to shift the absorption of rhodamine dyes toward the region 620-670 nm. The hydrophobic nature of all known long-wavelength dyes results in the tendency to form intra- and intermolecular aggregates in hydrophilic solvents, especially in aqueous environment. Due to the aggregation with biological materials, fluorescence quenching of the dyes is often observed. New strategies for prevention of these processes are considered. PMID- 24226793 TI - 6-Thioguanine luminescence probe to study DNA and low-molecular-weight systems. AB - 6-Thioguanine, an antitumor drug, has been tested as a luminescence probe to study DNA and cryoprotector solutions at temperatures between 4.2 and 273 K. The electronic structure of the tautomeric and ionic forms of 6-thioguanine is studied comprehensively both theoretically and experimentally. An excited-state diagram of 6-thioguanine N9H tautomer is proposed. The temperature behavior of 6 thioguanosine is examined in different cryoprotector solutions and with different aggregate states of solvents. Structure and phase transitions in low-molecular weight cryoprotectors (glycerol, ethanol, propanediol, DMSO) and their water solution are investigated in the 4.2-273 K temperature range. New structural transitions in propanediol-water solutions are found in the temperature interval 10-180 K. DNA solutions are investigated by using 6-thioguanine incorporated in DNA by the method of biosynthesis. Phosphorescence intensity curves for 6 thioguanosine in native DNA manifest peculiarities at 21, 64, 87, 140, 180, and 268 K. PMID- 24226794 TI - Fluorescence spectroscopy of monoclonal antibodies produced against the fluorescyl hapten conjugated through the xanthene ring. AB - Two mouse anti-fluorescyl monoclonal antibodies (mAb), clones FL43.1 and FL55.3, were produced to the fluorescein hapten, which was conjugated to the carrier protein through the 4' position of the xanthene ring. Association constants (K A) and thermodynamic parameters for both mAb were ascertained by monitoring the steady-state intrinsic and fluorescein fluorescence. Both techniques were in good agreement and gaveK A values in the 10(9) M (-1) range. Ligand-induced intrinsic fluorescence quenching showed a hypsochromic shift for mAb FL43.1, but not for FL55.3, suggesting that the ligand interacts with different tryptophan residues in each mAb. Because these mAb are directed toward the phenylcarboxylate portion of fluorescein, the different ionic and structural forms should be useful as indicators of antibody binding site pH and buffering capacity near the binding site. PMID- 24226795 TI - Polarized fluorescence and absorption spectroscopy of 1,32-dihydroxy dotriacontane-bis-rhodamine 101 ester. A new and lipid bilayer-spanning probe. AB - We report on the properties of 1,32-dihydroxy-dotriacontane-bis-rhodamine 101 ester (Rh101C32Rh101) in lipid bilayers of 1,2-dioleoyl-sn-glycero-3 phosphocholine (DOPC) and in liquid solvents. The results are compared with those of rhodamine 101 octadecanyl ester (Rh101C18). Both molecules are solubilized in the lipid bilayer and the Rh101 moieties are anchored in the lipid-water interface, so that the electronic transition dipole moments (S 0 <->S 1) are oriented preferentially in the plane of the bilayer. At low concentrations of the dyes in lipid bilayers of DOPC, the fluorescence relaxation is single exponential with a lifetime of tau=4.9+/-0.2 ns. The relative fluorescence quantum yield of PhiC32/PhiC18 ~ 0.95 in DOPC vesicles. These results strongly suggest that only a small fraction of the Rh101C32Rh101 molecules are quenched, by, for example, intra- or intermolecular dimers in the ground state at mole fractions of less than 0.1% in the lipid bilayers. For Rh101C32Rh101 in lipid vesicles, the steady state and time-resolved fluorescence anisotropies are compatible with efficient intramolecular electronic energy transfer. It is concluded that nearly every Rh101C32Rh101 molecule is spanning across the lipid bilayer of DOPC. PMID- 24226796 TI - Spectral inhomogeneity and wavelength-dependent rotation of probe molecules in membranes. AB - Using subnanosecond laser spectrofluorometry, the spectral and polarization time resolved characteristics of 1-phenylnaphthylamine (1-AN) fluorescent probe in phospholipid bilayer and red blood cell (RBC) membranes have been studied. It is shown that the electronic spectra of the probe in model-membranes are inhomogeneously broadened. In contrast to low-molecular weight solvents, there are two reasons for inhomogeneous broadening. The first is connected with different levels of location of probe molecules in the membrane. Inhomogeneous broadening due to the first factor has a static character. The second reason is similar to that of solutions and linked with fluctuations of solvate structure. This type of broadening has a dynamic character. The process of intermolecular relaxation in membranes is accompanied by the release of the free energy excess, which results in wavelength-dependent rotation of probe. PMID- 24226797 TI - Electronic absorption and emission spectral data and fluorescence quantum yields of bridgedp-oligophenylenes, bi- to deciphenyls, and related furans and carbazoles. AB - Absorption and fluorescence emission spectral data, as well as fluorescence quantum yields (Phif), were determined for 41p-oligophenylene compounds containing 2-6, 8, and 10 benzene rings. Of 29 compounds containing carbon bridged rings (fluorenes), 28 were dialkylated on each bridge for improved solubility and photostability. Absorption maxima for oligophenylenes were observed at wavelengths as long as 366 nm, emission maxima to 437 nm, and molar extinction coefficients (E) as large as 153,000 L/mol-cm; all three exceeded predicted maximum values for the corresponding unbridged oligophenylenes. The substitution of furan for benzene or carbazole for a fluorene (two examples each) bathochromically shifted absorption and emission maxima. Dialkylated carbon bridges bathochromically shifted absorption and emission maxima, and lowered Phif in biphenyl and in one terphenyl analogue, but appeared to cause no diminution of Phif in higher oligophenylenes. Bis(2-methoxyethyl) substitution on the bridges, incorporated to provide solubility in polar solvents, lowered Phif in all examples. Tertiary alkyl substituents on terminal rings bathochromically shifted the absorption and emission maxima and generally increased Phif. The "loose bolt" effect, which lowers Phif in mononuclear substituted benzenes, may operate in 9,9 dialkylfluorenes, but not in 2,7-di-t-butylfluorene or in higher oligophenylenes. Cyclic ether and methoxy substituents as auxofluors on terminal rings generally bathochromically shifted absorption and emission maxima and increased E and Phif. Cyano substituents bathochromically shifted absorption and emission maxima, and increased E, but lowered Phif slightly. PMID- 24226798 TI - The use of parent material/slope positions as soil mapping units in irrigation soil surveys of Northern Nigeria. AB - The problems of different mapping units which hitherto formed the basis for irrigation soil surveys of the savanna landscapes in Nigeria are discussed. Using data from a semi-detailed soil survey, the possibility of establishing the major variations in soil properties which are relevant to irrigation by using a combination of parent material and slope position as mapping units are examined. In the mapping units considered, thirteen topsoil and eleven subsoil properties are significantly different between mapping units and have smaller variances within than between the mapping units. The variations of these topsoil and subsoil properties are also adequately accounted for by using parent material/slope position as a basis for mapping, suggesting that units based on parent material/slope position are of high utility for establishing the irrigation potentials of areas at the feasibility level of survey. PMID- 24226799 TI - Butyltin and copper monitoring in a Northern Chesapeake Bay marina and river system in 1989: An assessment of tributyltin legislation. AB - This study was designed to: (1) evaluate dibutyltin (DBT) and tributyltin (TBT) bi-weekly in the water column for four months during the peak boating season (June-September, 1989) at seven stations in the Back Creek and Severn River area of Maryland waters of Chesapeake Bay; (2) compare butyltin values from the 1989 study with values obtained from a similar butyltin monitoring study conducted in 1988 (after Maryland TBT legislation) and 1986 (before Maryland TBT legislation); (3) determine the extent of TBT paint use in the Back Creek area by surveying boat owners; (4) determine dissolved copper concentrations from three of the seven stations bi-weekly during the four-month study; and (5) compare dissolved copper concentrations at these stations with previous copper data collected in 1988.Mean four-month DBT concentrations ranged from 10 to 73 ng/L at the seven stations. Highest DBT concentrations occurred at Station 1 in a marina; lowest concentrations occurred at Station 7 in the Severn River. Mean four-month TBT concentrations ranged from 177 ng/L at Station 1 (marina) to 21 ng/L at Station 7 (Severn River). Maximum TBT concentrations of 361 and 570 ng/L occurred at marina SDtations 1 and 3, respectively. Temporal trends in both DBT and TBT (station mean concentrations by date) showed that peak concentrations occurred during the early part of the boating season followed by reductions in late summer and early fall. Spike concentrations of both DBT (117 and 62 ng/L) and TBT (308 and 366 ng/L) were reported on two sampling dates near a boat maintenance facility in Back Creek.There was a significant reduction in DBT concentrations from 1986 to 1989 when date was treated as a fixed effect. However, TBT concentrations were not significantly reduced between 1986 and 1989 when mean concentrations of TBT were averaged across stations and dates for each year. A significant reduction was reported at Station 1 (marina station) when each station was examined for differences between years. TBT was also reported to significantly decrease (p=0.0442) at Station 7 between 1988 and 1989. A boat owner survey in the study area showed that 6% of the recreational boats that were surveyed were painted with TBT paint in 1989. This was a significant decrease in TBT paint use from the previous year when 31% of recreational boat owners surveyed used TBT paints.An evaluation of dissolved copper concentrations at three stations in the study area in 1989 showed that mean concentrations from bi-weekly sampling for four months was 10 MUg/L at Station 1, 7.8 MUg/L at Station 4 and 2.7 MUg/L at Station 7. Copper concentrations decreased with distance away from the Back Creek marinas. Copper concentrations at all three stations were significantly lower in 1989 than in 1988. PMID- 24226800 TI - Economics of ground-water quality monitoring: A survey of experts. AB - The cost of a monitoring program can be easily ascertained in terms of the expenditures incurred for such items as personnel, supplies, field visits, instrumentation and laboratory analyses. The benefits of a monitoring program, however, cannot be easily evaluated due to the diversity of objectives for which monitoring programs are initiated and operated. The case study and the results of the follow-up exploratory survey reported in this paper were intended to capture the objective as well as the subjective reasons employed by a group of experts in responding to selected socio-economic questions related to the design of monitoring programs. Ninety-seven individuals, through a formal questionnaire, participated in the survey. They showed definite preferences, although there was some variability in responses due to such factors as residential status, institutional affiliation, education, and the length of professional experience. It was clear that the respondents favored the inclusion of cost-effectiveness criteria in monitoring programs; were ambivalent to the idea of initiating a regulatory program to monitor the wells of a large number of private owners; and if such a program were to be initiated they recommended that individual well owners share the bulk of the financial burden. Preliminary results from such exploratory surveys can lead to the framing of insightful research questions or hypotheses for further evaluation. Confirmatory testing of such questions or hypotheses in real world settings is a valuable area for further research. PMID- 24226801 TI - Effects of Cu(2+), Pb (2+) and Zn (2+) on voltage-activated currents in Helix pomatia L. Neurons. AB - Effects of Cu(2+), Pb(2+) and Zn(2+) were studied on voltage-activated Na-, Ca-, and K-currents in snail neurons. It was found that: 1. In normal physiological saline Cu(2+), Pb(2+) and Zn(2+) ions exerted complex changes on the total ionic currents; 2. All three metal ion have depressed the inward Na-currents but with different K D , moreover Pb (2+) increased Na-current at low concentrations (5 MUM); 3. The inward Ca-current was also reduced. The sequence of the blocking effect of metals was different: Pb>Cu>Zn, however the steady-state inactivation was influenced only by Cu(2+); 4. Outward currents were decreased in all neurons by Cu(2+), but the effects of Pb(2+) and Zn(2+) were either depression or enhancement in different indentified neurons; 5. The possibility of binding heavy metals to wide variety of membrane proteins and the observed effects on different ionic channels suggest that the metal effect is complex and cannot be taken as a specific one to a single channel type or site of location. PMID- 24226802 TI - Correlation between environmental parameters and leaf injury in Nicotiana tabacum L. cv. 'Bel-W 3'. AB - Tobacco plants (Nicotiana tabacum L. cv. 'Bel-W3') were exposed to ambient air for 25 weeks during the 1987 growing season next to an air pollution monitoring station in Brera (Milan, Italy). The research objective was to study the influence of selected environmental parameters on leaf damage in this plant, which is widely used as an ozone indicator. A multiple linear correlation model was estimated between leaf damage and available meteorological and air pollution data. Leaf injury was positively correlated with ozone integrated exposure and temperature, but negatively with vapour pressure deficit. A linear correlation model was used to estimate ozone integrated exposure from the leaf injury index. PMID- 24226803 TI - Population Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda. AB - Pregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether-lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether-lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e83; doi:10.1038/psp.2013.59; advance online publication 13 November 2013. PMID- 24226804 TI - Accelerated thrombolysis for pulmonary embolism: will clinical benefit be ULTIMAtely realized? PMID- 24226805 TI - Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. AB - BACKGROUND: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS: Fifty-nine patients (63+/-14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio >=1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28+/-0.19 at baseline to 0.99+/-0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20+/-0.14 and 1.17+/-0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30+/-0.20 versus 0.03+/-0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS: In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166997. PMID- 24226806 TI - Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. PMID- 24226807 TI - Association between insomnia symptoms and mortality: a prospective study of U.S. men. AB - BACKGROUND: Insomnia complaints are common in older adults and may be associated with mortality risk. However, evidence regarding this association is mixed. Thus, we prospectively examined whether men with insomnia symptoms had an increased risk of mortality during 6 years of follow-up. METHODS AND RESULTS: A prospective cohort study of 23,447 US men participating in the Health Professionals Follow-Up Study and free of cancer, reported on insomnia symptoms in 2004, were followed through 2010. Deaths were identified from state vital statistic records, the National Death Index, family reports, and the postal system. We documented 2025 deaths during 6 years of follow-up (2004-2010). The multivariable-adjusted hazard ratios of total mortality were 1.25 (95% confidence interval [CI], 1.04-1.50) for difficulty initiating sleep, 1.09 (95% CI, 0.97-1.24) for difficulty maintaining sleep, 1.04 (95% CI, 0.88-1.22) for early-morning awakenings, and 1.24 (95% CI, 1.05-1.46) for nonrestorative sleep, comparing men with those symptoms most of the time with men without those symptoms, after adjusting for age, lifestyle factors, and presence of common chronic conditions. Men with difficulty initiating sleep and nonrestorative sleep most of the time had a 55% (hazard ratio, 1.55; 95% CI, 1.19-2.04; P-trend=0.01) and 32% (hazard ratio, 1.32; 95% CI, 1.02-1.72; P-trend=0.002) increased risk of cardiovascular disease mortality, respectively, relative to men without those symptoms. CONCLUSION: Some insomnia symptoms, especially difficulty initiating asleep and nonrestorative sleep, are associated with a modestly higher risk of mortality. PMID- 24226809 TI - Distribution of trace elements in the mammalian retina and cornea by use of particle-induced X-ray emission (PIXE): localisation of zinc does not correlate with that of metallothioneins. AB - Proton-induced X-ray emission (PIXE) in combination with 3D depth profiling with Rutherford backscattering spectrometry (RBS) was used to establish the distribution and concentration of trace elements within individual corneal and retinal areas in frozen sections from adult male Wistar rats (n = 6). The distribution of endogenous trace elements in the cornea and retina is non homogenous. The most abundant metal in the cornea is calcium followed by zinc. Iron and copper are present in small amounts localised particularly to the epithelium. Iron is also identified in keratocytes. Relatively high levels of calcium occur in the corneal epithelial cell bodies. Zinc has a wide intense distribution across the corneal epithelium (with greater levels in the basal part) and posterior stroma. In the retina, zinc is the most common metal followed by iron and copper. Relatively high levels of zinc exist in the retinal pigment epithelium (RPE), photoreceptor inner segments (RIS) and inner nuclear layer (INL). Chelatable zinc was localised with fluorescent TSQ in the RPE, RIS and plexiform layers. It is interesting to note that the highest levels of total zinc and the greatest intensity of chelatable zinc staining do not coincide. In the RPE and corneal epithelium, zinc co-localised with the zinc-containing metallothioneins (MT). However, there was a clear mismatch between the localisation of the most intense levels of zinc in the neuroretina (i.e. INL) and corneal posterior stroma with that reported for MT. For example, the presence of zinc is not particularly associated with the retinal ganglion cells, retinal area that contains MTs in significant amounts. While high amounts of zinc are present in the INL and corneal posterior stroma, which are largely devoid of MTs. This probably represents pools of static, catalytic and structural zinc associated with substances other than the MTs. PMID- 24226808 TI - High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. AB - BACKGROUND: High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. METHODS AND RESULTS: At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (>=1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels >=23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42-2.78), P=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05-6.70), P<0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11-1.86), P=0.0250. Adding hs-TnI levels to the CHA2DS2VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. CONCLUSIONS: Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. PMID- 24226810 TI - Interactions of polymers with reduced graphene oxide: van der Waals binding energies of benzene on graphene with defects. AB - The interaction of benzene molecules with various defects in graphene is studied using density functional theory enhanced by two different recent dispersion corrections. Both provide the same qualitative picture: the binding strength of benzene to the various defects is governed by steric hindrance. Our first principles calculations in combination with a simple model predict reduced stabilities of polymer-graphene nanocomposites made of reduced graphene oxides depending on the defect density. Above ~15% defect coverage the interaction is lowered to roughly one third as compared to pristine graphene. PMID- 24226811 TI - The tangible common denominator of substance use disorders: a reply to commentaries to Rehm et al. (2013a). AB - In response to our suggestion to define substance use disorders via 'heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, 'heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorder. PMID- 24226812 TI - Self-intoxication with baclofen in alcohol-dependent patients with co-existing psychiatric illness: an emergency department case series. AB - AIMS: The aim of the study was to describe the characteristics and management of alcohol-dependent patients with co-existing psychiatric illness seen after self intoxication with oral baclofen in an emergency department (ED). METHODS: A retrospective review of medical records of such patients over a 12-month period from January 2012. RESULTS: Twelve such patients were identified, median age 39.5 years. The median supposed ingested dose of baclofen was 340 mg (range 140-800 mg). Three patients who had co-ingested benzodiazepines had a decreased level of consciousness (Glasgow Coma Scale <8) and flumazenil had been given to reverse coma. Blood alcohol concentration, requested for all patients, was positive in three (ranging from 153 to 495 mg/100 ml). Gastric lavage was performed in two cases. All patients made a full recovery. They were discharged from the ED or intensive care unit after psychiatric assessment. CONCLUSION: Baclofen overdose affects the autonomic and central nervous system. Supportive care is symptom based. Care should be taken when prescribing baclofen with other central nervous system depressants and to patients with past attempted suicide. PMID- 24226813 TI - Excellent electrochemical properties of yolk-shell LiV3O8 powder and its potential as cathodic material for lithium-ion batteries. PMID- 24226814 TI - A new type of DNA "light-switch": a dual photochemical sensor and metalating agent for duplex and G-quadruplex DNA. AB - Ru(bpy)2dppz, a well studied "light-switch" metal complex, transforms into a photochemical "light-switch" and DNA damaging agent by incorporating structural strain. This distorted compound is photoreactive and ejects a ligand upon binding duplex and G-quadruplex DNA, producing a reactive metal center that metalates the DNA. PMID- 24226815 TI - Transgenic Brassica napus plants obtained by cocultivation of protoplasts with Agrobacterium tumefaciens. AB - Hypocotyl protoplasts of German winter oilseed, rape (Brassica napus) lines of double-low quality were transformed using Agrobacterium tumefaciens harbouring pGV 3850?1103 neo (dimer) containing chimaeric kanamycin resistance reporter genes. Transformed protoplasts were regenerated to fertile and phenotypically normal plants. Transformation was confirmed by kanamycin resistance, nopaline production, neomycinphosphotransferase II activity, and Southern blot hybridization. Seed progeny from self-pollinated transformants expressed the introduced kanamycin resistance as a Mendelian trait. PMID- 24226816 TI - Kanamycin sensitivity of cultured tissues of Vitis. AB - The kanamycin sensitivity of callus growth and adventitious shoot and root formation was studied in several cultivars of Vitis vinifera L. and in V. rupestris Scheele cv. St. George to investigate the suitability of kanamycin resistance as a selectable marker for grape transformation. Kanamycin concentrations ranged from 0 to 30 mg/l. Carbenicillin was added to the medium in all experiments at concentrations of 500 or 250 mg/l, as normally used in cocultivation experiments with Agrobacterium. Callus formation, root initiation, and adventitious shoot formation were completely inhibited by 20, 10, and 7 mg/l kanamycin, respectively; suggesting that these are the minimum concentrations that should be necessary to select transformed plants. Carbenicillin produced inhibitory effects that sometimes resembled those of growth regulators. The high kanamycin sensitivity of adventitious shoot formation in grape exceeds that reported for any other plant species and is likely to hinder the recovery of transformed plants. PMID- 24226817 TI - Atrazine and diuron resistant plants from photoautotrophic protoplast-derived cultures of Nicotiana plumbaginifolia. AB - Atrazine and diuron resistant clones were isolated from diploid photoautotrophic protoplastderived colonies of Nicotiana plumbaginifolia. Protoplasts were mutagenised with 0.1 mM N-ethyl-N-nitrosourea and colonies were screened for resistance after plating. Selection of calli was carried out on their ability to grow and green on a selective medium containing either atrazine or diuron. Plants were regenerated from most tolerant calli. Herbicide spray showed that plants of 6 and 4 clones were resistant to atrazine and diuron, respectively. PMID- 24226818 TI - Transformation of Cucumis sativus tissue by Agrobacterium tumefaciens and the regeneration of transformed plants. AB - Cotyledons of cucumber seedlings (Cucumis sativus L. cv. Poinsett 76) were co cultivated with disarmed Agrobacterium strain C58Z707. The Agrobacterium strain contained the Agrobacterium-derived binary vector plasmid pGA482, its T-DNA region contains a plant expressible bacterial derived neomycin phosphotransferase II (NPT II) gene which upon transfer, genome integration, and expression in plant tissues confers resistance to the antibiotic kanamycin. After growth of inoculated cotyledon sections on selective medium containing 100 mg/l kanamycin, transformed embryogenic calli were obtained followed by the development of embryos and plant regeneration. Transformed R0 and R1 cucumber plants appeared normal and tested positive for NPT II enzyme activity. Genomic DNAs isolated from the NPT II positive plants all showed hybridization to the characteristic 2.0 kb (BamHI to HindIII) NPT II gene-containing fragment. These results show that the Agrobscterium-mediated gene transfer system and regeneration via somatic embryogenesis is an effective method for the transfer of genetic material into plant species belonging to the family Cucurbitaceae. PMID- 24226819 TI - Transmission of paternal chloroplasts in tobacco (Nicotiana tabacum). AB - Medgyesy et al. (1986, Mol. Gen. Genet. 204, 195-198) have described in Nicotiana plumbaginifolia and in an interspecific cross involving N. plumbaginifolia and N. tabacum a procedure for selecting cell lines derived from seedlings carrying paternal chloroplasts by taking advantage of a plastid-encoded mutation which confers resistance to streptomycin. We have extended their demonstration of occasional transmission of chloroplasts through pollen to the case of an intraspecific cross in N. tabacum. The line used as maternal parent, ITB19(sua), displayed a cytoplasmic male sterility due to the presence of a cytoplasm originating from N. suaveolens. The line used as paternal parent, SR1, was fertile and possessed mutant chloroplasts conferring resistance to streptomycin. From cell lines derived from 204 seedlings, three were regenerated into streptomycin-resistant buds. The plants derived from these three clones were male sterile. Their progeny, after crossing with a wild type tobacco line, XHFD8, was resistant to streptomycin. Tests of resistance of the seedlings to tentoxin and restriction analyses of the chloroplast DNA indicated that two clones still had the maternal chloroplasts and were thus probably new streptomycin-resistant mutants, whereas the third one had acquired the chloroplasts of the paternal parent, but had retained the mitochondria of the maternal parent. PMID- 24226820 TI - Fertile Indica rice plants regenerated from protoplasts isolated from microspore derived cell suspensions. AB - Rice plants (Oryza sativa L., Chinsurah Boro II var. Indica) were regenerated from protoplasts isolated from microspore derived cell suspensions. A simple procedure for the establishment of such cell suspension cultures from embryogenic microcallus derived from cultured isolated microspores of Indica-type rice is described. Regenerating protoplasts could readily be isolated from 5-12 months old cell suspensions showing visible colony formation in the range of 180-1050 colonies/10(6) protoplasts after about one month in culture. More than 100 independent green plantlets were regenerated via secondary embryogenesis from ca 20*10(6) protoplasts. Out of 32 plants grown to maturity under greenhouse conditions 24 were fertile. PMID- 24226821 TI - The accumulation of podophyllotoxin-beta-D-glucoside by cell suspension cultures derived from the conifer Callitris drummondii. AB - Podophyllotoxin was produced by cell cultures derived from needles of Callitris drummondii. The needles of this conifer contained 1.56% podophyllotoxin on a dry weight basis, 32% being present in the beta-glucosidic form. Trace amounts of desoxypodophyllotoxin and matairesinol were also detected. In dark-grown cell cultures, ca. 0.02 % podophyllotoxin was accumulated, 85-90 % in the beta-D glucosidic form. Moreover, traces of the lignans matairesinol, hinokinin and asarinin were detected. Illumination stimulated the endogenous production of podophyllotoxin-beta-D-glucoside; contents of up to 0.11 % could be measured. PMID- 24226822 TI - Production of canthin-6-one alkaloids by cell suspension cultures of Brucea javanica (L.) Merr. AB - Cell suspension cultures of Brucea javanica (L.) Merr. were used to determine culture growth characteristics and production of canthin-6-one alkaloids. The major alkaloids produced were canthin-6-one, 11-hydroxycanthin-6-one, 5 methoxycanthin-6-one and 11-methoxycanthin-6-one. Alkaloids were synthesised throughout the 36 day growth cycle of the cells with maximum amounts within the cells occurring between days 20 to 28; approximately 10% of the alkaloids were in the medium at day 24 rising to 45% at day 32. PMID- 24226823 TI - Wheat germ agglutinin in wheat seedling roots: induction by elicitors and fungi. AB - Treatment of wheat (Triticum aestivum L.) seedlings with elicitors originating from either plant or fungal cell walls induces about a 2-fold increase of wheat germ agglutinin (WGA) in the roots. While the WGA content in roots of healthy plants normally decreases as a function of germination time, a transient accumulation of WGA could be observed in plants challenged with different fungi, including Rhizoctonia solani, Fusarium culmorum, Pythium ultimum and Neurospora crassa. Peak levels in challenged roots were 2 to 5 times as high as in control plants. Most of this induced WGA could be released from the roots by soaking them in a solution of the hapten N-acetylglucosamine. On the basis of the results obtained it is postulated that WGA may be involved in the defence of wheat against fungal attack. PMID- 24226824 TI - Plant regeneration from root callus protoplasts of sour cherry (Prunus cerasus L.). AB - Callus protoplasts of sour cherry clone CAB4D entered sustained division in Murashige and Skoog's (1962) medium with 1-naphthaleneacetic acid, 6 beneylaminopurine and zeatin. Further to callusing, organogenesis was induced from the protoplastderived callus, in a basal regeneration medium with these same growth regulators at 0.01 mg/l, 2,0 mg/l and 0.05 mg/l, respectively. The regeneration pathway, from such callus, could be altered by adding different organic compounds to this medium. Casein hydrolysate, added alone, promoted rhizogenesis, with shoot buds regenerated from the protoplast-derived roots, while in a basal regeneration medium with casein hydrolysate and a group B vitamin mixture direct caulogenesis occurred. PMID- 24226825 TI - Evidence for quantitative responses during co-culture of Pyrus communis protoplasts and Erwinia amylovora. AB - Mesophyll protoplasts were isolated from axenic shoot cultures of pear cultivars, exhibiting different degrees of susceptibility to fire blight infection at the whole plant level and they were co-cultured with the wild-type strain CFBP 1430 of Erwinia amylovora, and with an avirulent transposon mutant of the former (PMV 6046). Results, as assessed in terms of the effects of bacteria on protoplast viability, the time to the onset of divisions, the percentage of the originally cultivated protoplasts that divided once and of those proliferating to give 10 cell colonies, correlated with field resistance to fire blight of the respective pear genotypes. These results might provide a model for a better understanding of the interaction between pear and E. amylovora. PMID- 24226826 TI - Agrobacterium tumefaciens-mediated transformation of Pisum sativum L. using binary and cointegrate vectors. AB - Epicotyl segments and nodus expiants from etiolated seedlings of Pisum sativum were transformed using Agrobacterium tumefaciens strains GV 2260 (p35S GUS INT) and GV 3850 HPT carrying either a neomycin- or hygromycinphosphotransferase-gene as selectable markers. The transgenic character of hygromycin- or kananamycin resistant tissue was confirmed by detection of nopaline or neomycinphosphotransferase-II- and beta-glucuronidase activity in crude extracts of resistant tissues. Up to 5 % of developing shoots from shoot proliferating nodi were regenerated via organogenesis to kanamycin-resistant plantlets. Transformation frequency in vitro was found to be influenced by expiant source, A. tumefaciens strain, pea genotype and duration of cocultivation. Acetosyringone did not increase the transformation rate. PMID- 24226827 TI - Rapid multiplication of adventitious somatic embryos in peach and nectarine by secondary embryogenesis. AB - Somatic embryos were multiplied by secondary embryogenesis in cotyledonary cultures of peach and nectarine (Prunus persica L.) using a simplified culture medium for immature seeds. A three-stage process with an initial callus phase was established in darkness on a medium containing basal salts (modified MS) supplemented with 2,4-D (5 mg/l), Kn (2 mg/l) and BAP (2 mg/l) and casein hydrolysate (500 mg/l). This was followed by a growth regulator-free medium with activated charcoal for the adventitious and direct multiplication of somatic embryos under continuous light. Somatic embryos (10-15) originated from the epidermal layer of primary somatic embryos of 4-6 mm size. The incidence of morphologically abnormal embryos was reduced by subculturing every 20 days. Calli which were isolated and grown on a 2,4-D medium were more embryogenic than those on NAA. These embryos multiplied continuously for more than 10 months by a repetitive somatic embryogenic process. A third stage medium, supplemented with BAP (2 mg/l), was required for axis elongation, germination and transfer to soil. PMID- 24226828 TI - The effect of antibiotics on the inhibition of callus induction and plant regeneration from cotyledons of sugarbeet (Beta vulgaris L.). AB - Callus induction and plantlet regeneration from cotyledonary expiants of sugarbeet was observed utilizing two media formulations, MS and a modified MS termed RVIM both supplemented with 1.0 MUg/ml BAP as the sole growth regulator. Callus induction was genotype dependent The USDA line 8787 produced the highest response for callus induction followed by 'Betaseed 4587' and the USDA line C600. This order was conserved on both media formulations. Shoot induction was consistently higher averaging 32% from the RVIM formulation over the 3 genotypes compared to 25% from MS. The antibiotics geneticin, gentamycin, hygromycin, kanamycin and phleomycin were screened with the modified RV system utilizing 'Betaseed 4587'. Callus growth was inhibited by levels of 50 MUg/ml geneticin, 150 MUg/ml gentamycin, 10 MUg/ml hygromycin, 150 MUg/ml kanamycin and 20 MUg/ml phleomycin. The results indicate that the concentrations of antibiotics used to inhibit callus induction will be sufficient for use as selectable markers in transformation experiments with Beta vulgaris. PMID- 24226829 TI - Plant regeneration from protoplasts isolated from seedling cotyledons of Stylosanthes guianensis, S. macrocephala and S. scabra. AB - Plant regeneration from protoplasts is a prerequisite to the production of modified plants using somatic hybridization and transformation. Whole plant regeneration was achieved from protoplasts isolated from seedling cotyledons of Stylosanthes guianensis, S. macrocephala and S. scabra, three economically important species of this tropical forage legume genus. The effects of both protoplast density and protoplast culture method on cell division and plating efficiency are presented. PMID- 24226830 TI - Suspension feeding in ciliated protozoa: Functional response and particle size selection. AB - The quantitative uptake of latex beads of different sizes and of live cells by 14 species of ciliates was studied. The functional response (uptake rate as function of food particle concentration) can be fitted to a hyperbolic function and this can be explained in terms of the function of the mouth apparatus. Each species shows a distinct size spectrum of particles which are retained and ingested. These size spectra may be explained by mouth morphology, and particle size selection may play a role for niche separation of coexisting ciliates. Most bacterivorous holotrich ciliates retain particles down to 0.2MUm and in one case down to 0.1MUm; they retain particles between 0.3 and 1MUm most efficiently. The spirotrich ciliates investigated do not retain particles smaller than 1-2MUm. PMID- 24226831 TI - Suspension feeding in ciliated protozoa: Feeding rates and their ecological significance. AB - The quantitative uptake of suspended particles has been studied in 14 species of ciliated protozoa in terms of the maximum rate of water cleared at low particle concentrations and of the maximum ingestion rate at high particle concentrations. The results, supported by data from the literature, show that ciliates which feed on larger particles (> 1-5MUm) compare favorably with metazoan suspension feeders with respect to the ability to concentrate dilute suspensions of particles. Species specialized on smaller food particles (0.2-1MUm), the size range of most bacteria in natural environments, require a higher concentration of particles. Bacterial population densities which can sustain ciliate growth are found in sediments, waters rich in organic material, and in the early successional stages of decomposing organic material. This is not the case in open waters in general where bacterivorous ciliates cannot play a role as grazers of bacteria. PMID- 24226832 TI - Microspatial heterogeneity in the distribution of ciliates in a small pond. AB - Five transects of contiguous samples from the surface of a small pond and one transect from its bottom were collected in order to quantify microspatial heterogeneity in the distribution of ciliated protozoa. Examination of the frequency-abundance relations for these transects suggests that they can be approximated by negative binomial distributions with a commonk of 1.87. Contagiousness or crowding increases with population density.Mean patch size and mean interpatch distance were measured for 4 transects as 1.5 to 2 cm and 3 to 4 cm, respectively. This heterogeneity is suggested to arise from behavioral aggregation about discrete food sources and be very ephemeral.Blocking of adjacent contiguous samples was used to investigate the effect of sample size on the apparent correlation between the numbers of pairs of taxa. In all cases examined, taxa were relatively independent in their distribution at small sample sizes and became more negatively or positively associated as samples were combined. This may reflect that the small scale patches are essentially monospecific. PMID- 24226833 TI - Use of numerical profiles for studying bacterial diversity. AB - A total of 308 bacteria were isolated from oil-storage tanks. Of these 20% were unidentifiable, even at the generic level. A numerical scoring method differentiated between the isolates and was used to estimate the diversity of the bacterial communities in the tanks over a period of 11 months. Although the scoring method suggested a higher diversity than did conventional identification, there was some consistency in the results produced by the two approaches. It is suggested that a scoring method based on only nine tests could be useful for estimating and comparing bacterial diversity in other habitats. PMID- 24226834 TI - Occurrence ofAeromonas hydrophila in limnetic environments: Relationship of the organism to trophic state. AB - The densities ofAeromonas hydrophila in various natural waters were found to be strongly correlated with a relative index proposed for use in trophic state assessments of fresh waters. No such correlation was found with the recoverable heterotrophic population of whichA. hydrophila is a part.A. hydrophila was found to be seasonally distributed with maximal densities occurring during summer through early fall. It was also found to be spatially distributed within a pond with the most consistent densities occurring from 1 m depth down to that depth in the water column where the temperature reaches 16 degrees C. The densities of the organism correlated most strongly with total phosphorus, chlorophylla, and Secchi depth. Moderate correlations were found with dissolved phosphorus, Kjeldahl nitrogen, and dissolved organic carbon. Little or no correlation was obtained with ammonia, orthophosphate, pH, alkalinity, or dissolved oxygen. The discriminating ability that theA. hydrophila density measurements provide in the oligotrophic through mesotrophic range appears to exceed those of presently available methods. The facility and sensitivity of the enumeration method forA. hydrophila should make it a useful tool for trophic state assessments. PMID- 24226835 TI - Composition of the saprophytic bacterial communities in freshwater systems contaminated by heavy metals. AB - The bacterial communities of three aquatic systems were analyzed in order to compare the influence of heavy metals. The first system was a sedimentation pond in a zinc-copper factory. The second was the bank of the Belgian river Meuse covered by the mossPlatyhypnidium riparioides (Hedw.) Dix. contaminated with heavy metals. The third was the bank of the same river covered by the same uncontaminated moss.The study was focused mainly on cadmium.The reciprocal averaging method showed that some bacterial strains could develop in very high concentrations of cadmium, but their physiological characteristics were not the same as those of the sensitive strains. In addition, the characteristics of the resistant strains depended on the environment. Correlation between resistance to heavy metals and to antibiotics was observed but was not the same in all communities. The density of resistant strains was roughly related to the level of toxicity in the environment. PMID- 24226836 TI - Positional variation in phylloplane microbial populations within an apple tree canopy. AB - Variation in density of epiphytic yeasts, filamentous fungi, and bacteria on apple leaves collected from eight trees at nine dates for two seasons was determined with respect to three positional factors: height, compass direction from the center of the tree, and lateral proximity to the canopy periphery. Univariate analyses of variance were performed on each of the microbial classes for each date according to a model that excluded tree effect but accounted for the positional factors with interactions. The assumption of no tree effect was explored by residual analysis and examination of the seasonal pattern of microbial densities for each tree. No persuasive evidence was obtained to invalidate this assumption. For filamentous fungi and yeasts, height and lateral position were the most significant factors withp<0.05 for yeasts at several periods. The two factors appeared to be of equal importance. Trends were less clear for bacteria, but all three positional factors and some two-way interactions seemed of some importance. For filamentous fungi and bacteria, frequently no factors were significant at a level of 0.10, but at almost all sampling dates certain positional factors and interactions were significant at a level of 0.25. Inspection of partial correlation coefficients indicated no apparent linear association between densities of most pairs of microbial classes. Implications of these results for experimental design and for the microbial ecology of the phylloplane community are discussed. PMID- 24226837 TI - Bacterial symbionts on green hydra and their effect on phosphate uptake. AB - Gram-negative rod-shaped bacteria (1.5-2MUm long and 0.5MUm wide) have been found associated with green hydra. They are always present on the hydra surface delineating the ectodermal cells, on animals in culture, and also on those sampled from a natural habitat. The bacteria could be removed by a 30-min treatment with antibiotics (50MU/ml polymyxin B and 50MU/ml streptomycin). Antibiotic-treated hydra took up 55% less phosphate from the medium than control hydra. The nutritional relationship between the bacteria and green hydra and possible routes of infection of the hydra by these prokaryotic symbionts are discussed. Their importance in interpreting results of certain types of physiological experiments using aquatic organisms is emphasized. PMID- 24226838 TI - [Alternative splicing--principles, functional consequences and therapeutic implications]. AB - Protein-coding genes in higher eukaryotes are transcribed as pre-mRNA in which the coding regions (exons) are separated by non-coding segments (introns). The exons are connected to form the mature mRNA in a process called splicing. In the case of alternative splicing an exon can be either included or skipped from the mature transcript leading to formation of several mRNAs from a single pre-mRNA. As over 90 % of all human genes are alternatively spliced, alternative splicing dramatically increases proteome diversity and fulfills important regulatory functions. This is underlined by mutations that interfere with splicing regulation and directly correlate with the formation of several diseases. Correction of these disturbed splicing processes has emerged as a promising therapeutic concept and has led to the development of several drugs that are currently being tested in clinical trials. PMID- 24226839 TI - First trimester maternal serum alpha-fetoprotein is not raised in pregnancies with open spina bifida. AB - BACKGROUND: Two recent studies have suggested that maternal serum alpha fetoprotein (AFP) levels are increased in the first trimester of pregnancies in which the fetus has an open spina bifida. This is contrary to previously published studies. This study assesses further whether maternal serum AFP is elevated in the first trimester in cases with open spina bifida. METHODS: Cases with open spina bifida were identified from our fetal database, and corresponding first trimester screening samples were retrieved and analysed for maternal serum AFP. A control group was selected by taking three samples matched for gestational age (exact day), ethnicity and smoking status and received in the laboratory on the same day. AFP was measured with the Kryptor platform and free beta-hCG and pregnancy-associated plasma protein A results were available from the fetal database. RESULTS: Thirty-nine open spina bifida cases were identified with a control group of 126 cases. The median multiple of the median AFP in the cases were not significantly different from the controls (0.92 vs 1.06 p = 0.3511) as was the case for free beta-hCG (0.87 vs 0.95 p = 0.7146) and pregnancy-associated plasma protein A (1.04 vs 1.04 p = 0.261). CONCLUSION: Our results confirm that maternal serum biochemical markers in the first trimester are unable to distinguish cases in which the fetus has open spina bifida. PMID- 24226840 TI - Editor's note. PMID- 24226841 TI - Introduction to the special issue on "psychological research and practice in organ transplantation". AB - This paper provides a brief overview of articles in this Special Issue on "Psychological Research and Practice in Organ Transplantation." The articles provide empirical information on the psychological adaptation of transplant candidates and recipients, as well as addressing the myriad ethical and clinical issues evident in the field of organ transplantation. Heart, liver, lung, kidney, and bone marrow transplantation for children and adults has increased in frequency in recent years, and the articles address the need for more sophisticated and comprehensive assessment of psychological concomitants. The Guest Editor's "Top Ten" list of research needs which transplantation psychologists might further address is discussed in this article. PMID- 24226842 TI - Psychological adjustment of pediatric lung transplantation candidates and their parents. AB - Investigated psychological functioning of 45 children and adolescents (ages 5 to 17 years) and their parents presenting at a major medical center for evaluation for lung transplantation. Patients completed self-reports, and parents completed measures on their children's behavior problems and emotional distress as well as on their own symptoms of distress. In general, children and their parents reported normal functioning on standard psychological measures. Few children fell in the clinically significant range, whereas 21% of mothers and 14% of fathers reported clinically significant levels of distress. Older children reported lower levels of depressive symptoms than younger children, and patients with cystic fibrosis manifested lower levels of internalizing symptoms than those with other pulmonary diseases. Findings demonstrate the resiliency of children and their parents facing a stressful point in the child's medical status and document the usefulness of psychological screening of patients and parents to identify those in need of clinical intervention. PMID- 24226843 TI - Psychological adjustment of children in the pretransplant phase of bone marrow transplantation: Relationships with parent distress, parent stress, and child coping. AB - Families of 22 children preparing to undergo bone marrow transplantation (BMT) provided information concerning parent-reported major negative life stress, child coping strategies, parental psychological symptomatology, and child adjustment. Immediately prior to BMT, children and families are confronted with multiple stresses which challenge the child's coping and strain the parents' ability to assist the child with coping. Hence, stress, parental adjustment (distress), and child coping may be important factors affecting the child's overall psychological adjustment. Results showed that 15-25% of children and parents experienced clinically significant levels of psychological distress. Parent and child psychological distress were closely related. Major negative life stresses experienced by the parent and use of avoidant coping by the child significantly predicted child adjustment problems in the pretransplant period. Coping skills interventions targeting avoidant coping and management of parental stress/distress may reduce child psychosocial risk prior to BMT. PMID- 24226844 TI - Depression and coping in candidates for kidney transplantation: Racial and ethnic differences. AB - Subjects were 288 adolescents and adults with end-stage renal disease who were candidates for kidney transplantation, a group identified at risk for noncompliance. The purpose was to examine racial and ethnic variations in coping variables that may underlie noncompliance and impact upon health outcome. Secondarily, the relationship between depression and particular styles of coping was investigated. Race/Ethnicity was divided into three categories: Black/Non Hispanic, White/Non-Hispanic, and Hispanic. Coping and depression were assessed using the COPE and Beck Depression Inventory, respectively. Results indicated that Hispanic and Black subjects were more likely to use maladaptive styles of coping and less likely to use adaptive coping than were White subjects and that Black subjects reported more physical symptoms of depression. These findings point to possible mechanisms underlying the occurrence of noncompliance and resulting poorer health outcome for individuals of different racial and ethnic groups. PMID- 24226845 TI - Coping strategies and psychological distress in cancer patients before autologous bone marrow transplant. AB - The increased use of bone marrow transplantation (BMT) to treat a variety of cancers has led researchers to study psychological functioning of BMT patients. The majority of studies conducted, however, has focused on adjustment after transplantation. Cancer patients' use of coping strategies before undergoing this procedure may also relate to levels of psychological distress. Our aims were (1) to provide normative coping data, controlling for situation-specific variables with a homogeneous sample, targeted stressor, and fixed time point, using the Ways of Coping Questionnaire; and (2) to identify coping strategies associated with distress before high-dose chemotherapy. Subjects were 49 patients scheduled to receive high-dose chemotherapy and an autologous bone marrow transplant. Consistent with previous coping research, we found that escape-avoidance was related to psychological distress on several measures. Item endorsement analyses of the escape-avoidance subscale suggest that patients may have used more passive than active avoidance strategies. Subsequent participation in a longitudinal study was not affected by initial levels of avoidant coping. PMID- 24226846 TI - Gender differences in patterns of emotional distress following heart transplantation. AB - The study provides the first empirical evaluation of gender differences in psychological symptomatology and DSM-III-R major depressive disorder (MDD) across the first year following heart transplantation. An important goal was to identify physical health-related and psychosocial factors that could account for, or mediate, any association between gender and psychological distress. The sample for the present analyses was drawn from a larger cohort of 172 heart recipients and included all 28 women in the cohort plus 118 men who were matched demographically with the group of women. Detailed patient assessments were completed at 2, 7, and 12 months posttransplant. As expected, women's symptom levels were consistently higher than men's. However, while men's symptom levels in all areas declined with time posttransplant, women's distress in the area of depression initially improved but then worsened by the 12-month assessment. The distribution of episodes of MDD showed a temporal pattern of gender differences similar to that of depressive symptoms. The most important mediators of the gender-depression relationship were factors related to early posttransplant daily functional limitations: women reported more impairments in daily activities. Higher levels of such impairments, in turn, predicted subsequently higher depression levels by 12 months posttransplant. Several additional variables pertaining to transplant-related concerns and a low sense of personal mastery while not serving as mediators-exerted their own independent effects on 12-month depression levels. The findings are relevant to the tailoring of educational and clinical interventions to the individual needs of women and men who receive heart transplants. PMID- 24226847 TI - Relapse prevention treatment for liver transplant patients. AB - This paper explores the utility of relapse prevention therapy (RPT) for transplant candidates with substance use disorders. Similarities and differences between this population and the general substance abuse patient population are discussed and suggestions are made for modifying the RPT treatment protocol. Major issues include the source and intensity of motivation for treatment, the nature of the therapeutic relationship, the type and severity of psychosocial consequences that may have been experienced as a result of substance use, and the patient's perception of the problem (addiction versus liver disease). Recommendations are made to provide empathy and support around medical concerns, motivate them for sobriety, and work to build collaborative relationships between team members and patients. Patients need to see the RP therapists as working to help them maintain sobriety and obtain a transplant, not as policing their drug use. PMID- 24226848 TI - Noncompliance in end-stage renal disease: A threat to quality of care and cost containment. AB - Noncompliance to treatment regimen after kidney transplantation is a threat to health outcomes and cost containment. Although there are methodological challenges to obtaining reliable compliance data, the results of noncompliance are increased morbidity and mortality in posttransplant patients. In addition, recent research suggests that patients who incur repeated rejection episodes leading to graft failure have higher levels of medical utilization. Some psychosocial factors related to compliance and medical utilization are potentially modifiable through cognitive-behavioral intervention. PMID- 24226849 TI - Cognitive functioning as a contraindication to organ transplant surgery: Dilemmas encountered in medical decision making. AB - A case is presented to illustrate some of the difficulties encountered when providing psychological consultation to evaluate the readiness of patients for pediatric heart-lung transplantation. The outcome of complex medical decision making can often hinge on information provided by the psychological consultant who is attempting to simultaneously serve the needs of the patient as well as the transplant team. Ethical dilemmas frequently arise when medical decision making is driven by limited health care resources and cost constraints. The utility of cognitive functioning as a variable in pediatric transplant decision making is discussed. Recommendations are made for further work in this area on both conceptual and empirical grounds to guide the integration of psychological information into transplant decision making as health care delivery continues to evolve in the future. PMID- 24226850 TI - Biomechanical testing of a beta-tricalcium phosphate wedge for advancement of the tibial tuberosity. AB - OBJECTIVES: to evaluate in vitro the strength of different compositions of beta tricalcium phosphate (beta-TCP) wedges in comparison with titanium foam and cages. To study the response to cyclic loading of the strongest beta-TCP wedge, titanium foam and titanium cage. METHODS: Compression test: Twenty-five tibiae were prepared for tibial tuberosity advancement using the modified Maquet technique. Five groups were defined depending on the material used to maintain the tibial tuberosity: Group 1=titanium cage; Group 2=wedges of porous titanium foam with 50% porosity (OrthoFoam(r)); Group 3=blocks of biphasic synthetic bone (60% hydroxyapatite [HAP] and 40% beta-TCP, porosity 80%); Group 4=blocks of biphasic synthetic bone (60% HAP and 40% beta-TCP, porosity 70%) and Group 5=blocks of biphasic synthetic bone (65% HAP and 35% beta-TCP, porosity 60%). Loads to failure were calculated for each implant. Cyclic study: Five additional tibiaes of group 1, 2 and 5 were fatigue tested from 100 to 500 N at a rate of 4 Hz for 200,000 cycles or until failure. RESULTS: Compression test: For the five groups, the mean load at failure was 1895 N, 1917 N, 178 N, 562 N and 1370 N respectively. Cyclical study: All samples in the three groups tested withstood 200,000 cycles without failure. CLINICAL SIGNIFICANCE: The ideal implant to maintain tibial tuberosity advancement after the modified Maquet technique would be absorbable and allow osteoconduction and osteoinduction. As such, beta-TCP wedges have many advantages and our study shows that they can withstand loads in the patellar tendon up to 500 N over 200,000 cycles in vitro and deserve more investigation. PMID- 24226851 TI - In vivo antitumor effect of an intracellular single-chain antibody fragment against the E7 oncoprotein of human papillomavirus 16. AB - Human papillomavirus (HPV)-associated tumors still represent an urgent problem of public health in spite of the efficacy of the prophylactic HPV vaccines. Specific antibodies in single-chain format expressed as intracellular antibodies (intrabodies) are valid tools to counteract the activity of target proteins. We previously showed that the M2SD intrabody, specific for the E7 oncoprotein of HPV16 and expressed in the endoplasmic reticulum of the HPV16-positive SiHa cells, was able to inhibit cell proliferation. Here, we showed by confocal microscopy that M2SD and E7 colocalize in the endoplasmic reticulum of SiHa cells, suggesting that the E7 delocalization mediated by M2SD could account for the anti-proliferative activity of the intrabody. We then tested the M2SD antitumor activity in two mouse models for HPV tumors based respectively on TC-1 and C3 cells. The M2SD intrabody was delivered by retroviral vector to tumor cells before cell injection into C57BL/6 mice. In both models, a marked delay of tumor onset with respect to the controls was observed in all the mice injected with the M2SD-expressing tumor cells and, importantly, a significant percentage of mice remained tumor-free permanently. This is the first in vivo demonstration of the antitumor activity of an intrabody directed towards an HPV oncoprotein. We consider that these results could contribute to the development of new therapeutic molecules based on antibodies in single-chain format, to be employed against the HPV-associated lesions even in combination with other drugs. PMID- 24226852 TI - Review by quality not quantity for better policy. PMID- 24226864 TI - Large NIH projects cut. PMID- 24226866 TI - Physicists plan to build a bigger LHC. PMID- 24226865 TI - Warsaw talks to thrash out UN climate roadmap. PMID- 24226867 TI - Mars mission set for launch. PMID- 24226868 TI - Social scientists hit back at grant rules. PMID- 24226869 TI - Preprints come to life. PMID- 24226870 TI - AIDS prevention: Africa's circumcision challenge. PMID- 24226871 TI - Malaria: A race against resistance. PMID- 24226877 TI - Research infrastructure: US shutdown should spur other nations. PMID- 24226878 TI - Impact: Take peer review into account. PMID- 24226879 TI - Antarctic: Riding shutdowns in developing world. PMID- 24226880 TI - Communication: Science is not about simple stories. PMID- 24226881 TI - Impact: Akin to quantifying dreams. PMID- 24226882 TI - Impact: China needs to review its metrics. PMID- 24226883 TI - Applied physics: A cascade laser's random walk. PMID- 24226884 TI - Solar System: Russian skyfall. PMID- 24226885 TI - Quantum physics: The right ambience for a single spin. PMID- 24226886 TI - Biodiversity: The ecological deficit. PMID- 24226887 TI - Sound and heat revolutions in phononics. AB - The phonon is the physical particle representing mechanical vibration and is responsible for the transmission of everyday sound and heat. Understanding and controlling the phononic properties of materials provides opportunities to thermally insulate buildings, reduce environmental noise, transform waste heat into electricity and develop earthquake protection. Here I review recent progress and the development of new ideas and devices that make use of phononic properties to control both sound and heat. Advances in sonic and thermal diodes, optomechanical crystals, acoustic and thermal cloaking, hypersonic phononic crystals, thermoelectrics, and thermocrystals herald the next technological revolution in phononics. PMID- 24226888 TI - Stabilizing the magnetic moment of single holmium atoms by symmetry. AB - Single magnetic atoms, and assemblies of such atoms, on non-magnetic surfaces have recently attracted attention owing to their potential use in high-density magnetic data storage and as a platform for quantum computing. A fundamental problem resulting from their quantum mechanical nature is that the localized magnetic moments of these atoms are easily destabilized by interactions with electrons, nuclear spins and lattice vibrations of the substrate. Even when large magnetic fields are applied to stabilize the magnetic moment, the observed lifetimes remain rather short (less than a microsecond). Several routes for stabilizing the magnetic moment against fluctuations have been suggested, such as using thin insulating layers between the magnetic atom and the substrate to suppress the interactions with the substrate's conduction electrons, or coupling several magnetic moments together to reduce their quantum mechanical fluctuations. Here we show that the magnetic moments of single holmium atoms on a highly conductive metallic substrate can reach lifetimes of the order of minutes. The necessary decoupling from the thermal bath of electrons, nuclear spins and lattice vibrations is achieved by a remarkable combination of several symmetries intrinsic to the system: time reversal symmetry, the internal symmetries of the total angular momentum and the point symmetry of the local environment of the magnetic atom. PMID- 24226889 TI - Evidence for high salinity of Early Cretaceous sea water from the Chesapeake Bay crater. AB - High-salinity groundwater more than 1,000 metres deep in the Atlantic coastal plain of the USA has been documented in several locations, most recently within the 35-million-year-old Chesapeake Bay impact crater. Suggestions for the origin of increased salinity in the crater have included evaporite dissolution, osmosis and evaporation from heating associated with the bolide impact. Here we present chemical, isotopic and physical evidence that together indicate that groundwater in the Chesapeake crater is remnant Early Cretaceous North Atlantic (ECNA) sea water. We find that the sea water is probably 100-145 million years old and that it has an average salinity of about 70 per mil, which is twice that of modern sea water and consistent with the nearly closed ECNA basin. Previous evidence for temperature and salinity levels of ancient oceans have been estimated indirectly from geochemical, isotopic and palaeontological analyses of solid materials in deep sediment cores. In contrast, our study identifies ancient sea water in situ and provides a direct estimate of its age and salinity. Moreover, we suggest that it is likely that remnants of ECNA sea water persist in deep sediments at many locations along the Atlantic margin. PMID- 24226892 TI - Low vitamin D levels are associated with symptoms of depression in young adult males. AB - OBJECTIVE: Results from studies examining associations between serum 25 hydroxyvitamin D (25(OH)D) concentrations and depressive symptoms are equivocal. We investigated the relationship between serum 25(OH)D concentrations and symptoms of depression, anxiety and stress in a cross-sectional analysis of a population-based sample of young adults participating in the Western Australian Pregnancy Cohort (Raine) Study. METHODS: Participants provided a blood sample at the 20-year follow-up (March 2010-April 2012) for the measurement of serum 25(OH)D concentrations. Mental health symptoms were assessed using the 21-item Depression Anxiety Stress Scales (DASS-21). Associations between serum 25(OH)D concentrations and total DASS-21 scores and subscale scores of depression, anxiety and stress were explored in males and females using negative binomial regression, adjusting for age, race, body mass index (BMI) and physical activity (n=735). Models examining subscale scores were also adjusted for the other subscale scores. RESULTS: After adjusting for confounders, an increase in serum 25(OH)D concentrations of 10 nmol/L decreased total DASS-21 scores in males by 9% (rate ratio (RR) 0.91; 95%CI 0.87,0.95; p<0.001) and depression subscale scores in males by 8% (RR 0.92; 95%CI 0.87,0.96; p=0.001). However, in adjusted models there were no significant associations between serum 25(OH)D concentrations and symptoms of anxiety and stress in males. There were no significant associations between serum 25(OH)D concentrations and symptoms of depression, anxiety and stress in females. CONCLUSIONS: We found an association between serum 25(OH)D concentrations and symptoms of depression, but not anxiety and stress, in males. Randomised controlled trials are necessary to determine any benefit of vitamin D supplementation in the prevention and treatment of depressive symptoms in young adults. PMID- 24226893 TI - Patterns of service utilisation in psychosis: findings of the 2010 Australian national survey of psychosis. AB - OBJECTIVE: This paper reports patterns of health service utilisation in the second Australian national survey of psychosis corresponding with changes in available services of this period. METHOD: Semi-structured interviews were carried out of an age-stratified random sample of adults who screened positive for psychosis. Multivariate logistic regressions were used to identify predictors of service use for a sample of 1825 individuals. RESULTS: Use of psychiatric inpatient services was associated with higher symptom levels, suicidal ideation, poor social functioning and younger age. High users of emergency mental health services similarly reported higher symptom levels, poor functioning and younger age, and also reported being married or in a de facto relationship. Recipients of general practitioner services had greater anxiety symptoms and suicidal thoughts, fewer negative symptoms, single marital status and English as their first language. Rehabilitation service use was associated with greater anxiety symptoms, unemployment, younger age of illness onset, living alone and having no dependent children living at home. Last, outpatient/community services were more frequently used by younger people with good premorbid adjustment, hallucinations and a less severe course of illness. CONCLUSIONS: Service utilisation patterns vary with the clinical and socio-demographic features of those who use them - inpatient and emergency service users being similar in such features and differing from users of other services. Comparison with the first national survey of psychosis revealed a significant decline in acute inpatient service use and a substantial increase in the use of outpatient/community and rehabilitation services over the past 10 years. PMID- 24226894 TI - Isotopic examination of links between diet, social differentiation, and DISH at the post-medieval Carmelite Friary of Aalst, Belgium. AB - Stable isotope ratios (delta(13) C and delta(15) N) were measured in human burials from the post-medieval (16th-18th c. AD) Carmelite friary burial grounds at Aalst, a town in Flanders, Belgium. Dietary patterns of 39 adult individuals were analyzed, from a mixed monastic and lay population buried in three different locations, reflecting groups with differing social status. The data show significant variation in the consumption of perhaps meat, but certainly also marine protein between females and males. This result represents a remarkable continuity with medieval dietary patterns, suggesting that the social and economic changes of the early modern period had a limited effect on everyday life. When both sexes were examined together, individuals buried in the cloister garth consumed significantly less marine protein compared to people buried in the church, likely reflecting social stratification. No statistical differences were observed between isotopic values from the church and the cloister alley, suggesting a similarly diverse diet of the monastic part of the buried population and that of the richer lay population. Finally, the hypothesis that diffuse idiopathic skeletal hyperostosis (DISH) is linked to a diet rich in animal protein was tested. No systematic or statistically significant differences between pathological and non-pathological bones from the same individuals affected with DISH were observed, and no statistical differences were found between individuals with DISH and individuals without DISH. PMID- 24226895 TI - Creatine turnover in the starry flounder,Platichthys stellatus. AB - Starry flounder (Platichthys stellatus) were cannulated and a bolus of 9 MUCi(14)C-creatine in saline was injected into the caudal vein. The fish were sacrificed at intervals ranging from 1h to 36d after label injection. Creatine pool size (PCr+Cr) and creatinine (Crn) content in blood, muscle, gills and liver were analyzed and specific activities (SA) determined.Mean concentrations of PCr+Cr/Crn in PCA-extracts of muscle, gills, liver and blood of experimental fish (at rest) were 38.1/2.40, 4.1/0.25, 5.6/0.45 and 0.3/n.d. MUmol.g(-1) respectively.Within 10 min, plasma SA had decreased by approximately 90%. In white muscle, the rate of(14)C-Cr appearance as well as label disappearance was slow compared to gills and liver. In fish examined 36d postinjection, mean SA in muscle had decreased to 23% of maximum SA which occurred 24h after injection.(14)C-Cr was incorporated into the liver tissue at a very high rate, SA being two orders of magnitude higher in liver than in white muscle. Over the first 6d, retention of label was observed in liver; after 36d only 3% of the original label was detected.Creatine pool size (PCr+Cr) in white muscle decreased with food deprivation. In flounder sacrificed after 36d, PCr+Cr was only 52% that of fed control fish, suggesting that creatine or precursors for its biosynthesis are supplied with the diet. PMID- 24226896 TI - Smoltification induced by a 'skeleton' photoperiod in underyearling coho salmon (Oncorhynchus kisutch). AB - Underyearling coho salmon fry were subjected to three initial photoperiod treatments (6L?18D, 10L?14D, 14L?10D) for two months and subsequently to three final treatments (16L?8D, 9L?6D?1L?8D, 10L?14D) in a factorial design. Growth rates and seawater adaptability were monitored regularly. The groups that were exposed initially to 6L?18D or 10L?14D and then to 16L?8D grew faster and had lower plasma sodium ion levels after seawater challenge tests than any of the other groups. Fish which were initially exposed to 6 L or 10 L daylength and then to a 9L?6D?1L?8D skeleton photoperiod, showed a slightly lower growth rate and seawater adaptability than those given the corresponding complete 16L?8D photoperiod. However fish maintained on skeleton photoperiods had significantly greater growth rates and seawater adaptability than those kept on the 10L?14D photoperiod. This indicates that it is not the accumulated number of hours of exposure to light that initiates smolting, but rather the time during the day when light is experienced. Fish exposed initially to 14L?10D showed little or no response to subsequent changes in photoperiod, suggesting that responsiveness to inductive photoperiods depends on the initial photoperiod treatment. PMID- 24226897 TI - The presence of 17alpha,20beta-dihydroxy-4-pregnen-3-one receptor activity in the ovary of the brook trout,Salvelinus fontinalis, during terminal stages of oocyte maturation. AB - The presence of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-DHP) oocyte receptor activity has been demonstrated in brook troutSalvelinus fontinalis. Scatchard analyses of the cytosol fraction during various terminal stages of oocyte maturation gave a high equilibrium association constant (Ka) value of 1.394+/-0.669 10(8)M(-1) (n=7) and low maximum binding capacities (Nmax). The association kinetics of the receptor was second order k+1=2.292*10(6)M(-1) sec(-1). The dissociation rate constant ka was 1.502*10(-2) sec(-1) for the first order dissociation reaction. The Ka=1.526*10(8)M(-1), when it was determined from k+1/k-1 a value close to that found from the Scatchard analysis. Competition studies showed the following binding affinities testosterone > 17alpha-HP > 17alpha,20beta-DHP > Promegestone > progesterone > estradiol > pregnenolone; cortisol showed no competitive inhibition. Cytosolic extracts when pre-equilibrated with various labelled steroids and eluted from a Sephacryl S-300 column gave multiple specific binding peaks. On sucrose density gradient centrifugation specific binding was observed at 3.05 S in cytosol containing 0.15M sodium chloride buffer. The receptor lost binding activity when incubated with various proteases, but DNase and RNase had no effect. Blood plasma without heparin at (1?10) dilution also bound [(3)H]17alpha,20beta-DHP, Ka was 8.04*10(7) M(-1).The nuclear pellet extract (750*g) gave very little specific binding activity even at high radiolabelled steroid concentrations and a linear Scatchard plot was not obtained. Nevertheless the nuclear extract, after dextran charcoal treatment, pre-equilibrated with [(3)H]17alpha,20beta-DHP, bound specifically to DNA cellulose, and cytosol from the same oocytes also bound to DNA cellulose under similar conditions. Although specific binding to DNA cellulose was obtained the salt concentrations at which the steroid-receptor complex elution took place was not reproducible in both nuclear extracts and cytosol samples. Also binding activity was extremely small compared to the total cytosolic binding. The nuclear extract when pre-equilibrated with high concentrations (20 nM) of the labelled steroid and then chromatographed on Sephacryl S-300 column gave a specific binding peak which was similar to that of the cytosolic preparation.The receptor levels in cytosol decreased progressively during final maturation (Stages 1-7). There is preliminary evidence for the presence of 17alpha,20beta-DHP receptor activity in cytosol of landlocked Atlantic salmonSalmo salar ouananiche, and rainbow troutSalmo gairdneri. The zona radiata fraction from late stages oocyes 5, 6, and 7 in brook and rainbow trout oocytes were isolated by ultracentrifugation; from this fraction a protein was characterized which covalently bound [(3)H]R5020 after photoaffinity labelling. The same protein also bound [(3)H]17alpha,20beta-DHP after solubilization in Brig 35 buffer. The SDS gel electrophoresis subunit composition of the above protein was similar to the cytosol counterpart binding [(3)H]17alpha,20beta-DHP, although the molecular weights were different. The blood sample [(3)H]R5020 binding component subunit composition was different from that of the membrane extracted protein. These results demonstrate the presence of 17alpha,20beta-DHP receptor activity in the cytosol and zona radiata membranes of the oocytes during final maturation. PMID- 24226898 TI - Comparison of whole body and tissue blood volumes in rainbow trout (Salmo gairdneri) with(125)I bovine serum albumin and (51)Cr-erythrocyte tracers. AB - Total, packed cell and, plasma volume estimates were made for the whole body and selected tissues of rainbow trout by the simultaneous injection of radiolabelled trout erythrocyte ((51)Cr-RBC) and radioiodinated bovine serum albumin ((125)I BSA) tracers. Blood volumes were estimated with both markers separately by the tracer-hematocrit method and as the combination of the(51)Cr-RBC packed cell and(125)I-BSA plasma volumes. Mean whole body blood volume was significantly less when calculated from the(51)Cr-RBC tracer data (3.52+/-0.78 ml/100 g; +/-SD) than when calculated with the(125)I-BSA tracer (5.06+/-0.86 ml/100 g) or as the sum of the two volumes combined (4.49+/-0.60 ml/100 g). The whole body hematocrit (28+/ 5%), estimated as the quotient of the(51)Cr-RBC volume divided by the sum of the(125)I-BSA and the(51)Cr-RBC volumes, also was significantly less than the dorsal aortic microhematocrit (36+/-4%). Estimates of total blood volumes in most tissues were significantly smaller when calculated from the(51)Cr-RBC data than when calculated by the other two methods. Tissue blood volumes were greatest in highly vascularized and well perfused tissues and least in poorly vascularized tissues. The relative degree of vascularization among tissues generally remained the same regardless of whether the red cell or the plasma tracer was used to calculated blood volume. It is not clear whether the expanded plasma volume is the result of the distribution of erythrocyte-poor blood into the secondary circulation or the result of extravascular exchange of plasma proteins. PMID- 24226899 TI - Some errors in respirometry of aquatic breathers: How to avoid and correct for them. AB - Respirometry in closed and flow-through systems is described with the objective of pointing out problems and sources of errors involved and how to correct for them.Both closed respirometry applied to resting and active animals and intermillent-flow respirometry is described. In addition, flow-through or open respirometry is discussed, in particular when the system is in non-steady state.Simulations are used to show how improper analysis can lead to improper conclusions. PMID- 24226900 TI - A study of diffusion models applied to dust emissions from industrial complexes. AB - Industrial complexes may release dust emissions through several to up to tens of stacks, as well as via fugitive area sources. Several diffusion models for small scale fugitive dust sources have been developed and combined with a point source model to form a series of models for industrial complexes. The applicable area of these models and the methods for obtaining the main parameters in the models have been tested and verified using measurement data gained from several field experiments. The models developed in this paper can give quite satisfactory results when compared to other current models. PMID- 24226901 TI - Effects of an oil spill on emergence and mortality in fiddler crabs Uca pugnax. AB - Following a spill of 567 000 gallons of No. 2 fuel oil into the Arthur Kill in New York and New Jersey in January 1990 we studied the emergence and mortality of fiddler crabs. We (1) compared seven salt marsh creeks immediately adjacent to the oil spill with 23 creeks at varying distances from the spill; (2) examined the temporal pattern of emergence in one creek; and (3) compared mortality rate of crabs that emerged with those we dug up. Twice as many crabs emerged in the adjacent creeks compared to those that were only 4.5km away. There were significant differences in the number of crabs that emerged as a function of distance from the spill. Crabs continued to emerge until mid-March. For all the emerged crabs, the percentage of females ranged from 28 to 80, whereas the percentage of females in intact burrows was 64-65%. For all emerged samples, females died earlier than males. In the laboratory, all emerged crabs died within four weeks whereas over 90% of the controls were still alive eight weeks after the initiation of the experiment. PMID- 24226902 TI - Carbon dioxide flux across a forest-field ecotone. AB - CO2 flux of a deciduous forest and an old-field surface, and the ecotone between these two typical southern U.S. ecological communities, was studied in July, 1989. Rates of CO2 flux were greatest in the old field and least in the forest plots. The ecotone showed the greatest variation in CO2 flux. These differences appear to be due to differences in soil surface temperature, the old field being more exposed to direct solar radiation. The ecotonal community represents a landscape property which should be considered in studies of the transfer of carbon across the soil-atmosphere boundary. PMID- 24226903 TI - Scaling methods in assessing environmental quality: A methodological approach to eutrophication. AB - The identification of pollution levels by numerical classification-ordination and the statistical confirmation of the detected trends-were attempted in a eutrophication assessment study. Special emphasis was placed on the importance of data scaling and the selection of a distance coefficient that would accentuate discrete states within the system. Among metric, binary and ordinal variable scaling, ordinal numbers showed the maximum sensitivity in discriminating pollution levels; the observed trends were further enhanced by using the absolute distance coefficient as a resemblance measure. The eutrophic patterns identified were statistically confirmed by a non-parametric permutation test. Finally a step by-step multivariate procedure is proposed for assessing environmental quality in aquatic ecosystems. PMID- 24226904 TI - Past and present water-quality conditions in the Hanford Reach, Columbia River. AB - Twelve water quality variables from upstream and downstream locations in the Hanford Reach of the mainstem Columbia River, southcentral Washington, were compared statistically for the two time periods 1951 to 1953 and 1986 to 1988. During the 1951 to 1953 period, beta radioactivity and, most likely, water temperatures in the Hanford Reach were significantly higher downstream than upstream, while dissolved oxygen and sulfate were significantly lower. The increased beta radioactivity and temperature downstream were due to the discharge of cooling water from five single-purpose production reactors then operating on the Hanford Site. The last production reactor closed in January 1971. During the 1986 to 1988 period, beta radioactivity and water temperatures were similar upstream and downstream, but nitrate nitrogen had become significantly higher downstream. Comparison of 1951 to 1953 with 1986 to 1988 showed, as expected, that beta radioactivity was much lower today, at essentially background levels. Phosphate in the Hanford Reach had decreased significantly over the 35 year interval, while biochemical oxygen demand, dissolved oxygen, and nitrate nitrogen had increased. These changes, while detectable statistically, were relatively small. Today, the quality of water in the Hanford Reach remains well within Washington State standards for Class A waters. Occasional low pH values, which appear to orginate upriver, violate these standards. PMID- 24226905 TI - Radon risk assessment: The effect of voluntary sampling distributions and bias. AB - This paper examines the problem of estimating indoor radon concentrations for radon-induced lung cancer risk assessment. Previous authors have identified various problems and possible corrections for the use of generally available radon screening measurements. Bias evident in data collected from volunteers is described; regional databases developed from voluntary data generally exhibit higher mean values than those obtained from random samples. Tools are developed to better characterize the differences in voluntary and random concentration distributions. Application is demonstrated using voluntary and random radon survey data for the state of North Dakota. PMID- 24226907 TI - Nonradiative excitation energy transport in one-component disordered systems. AB - High-accuracy Monte Carlo simulations of the time-dependent excitation probabilityG (s) (t) and steady-state emission anisotropyr M /r 0M for one component three-dimensional systems were performed. It was found that the values ofr M /r 0M obtained for the averaged orientation factor[Formula: see text] only slightly overrate those obtained for the real values of the orientation factor kappa ik (2) . This result is essentially different from that previously reported. Simulation results were compared with the probability coursesG (s) (t) andR(t) obtained within the frameworks of diagrammatic and two-particle Huber models, respectively. The results turned out to be in good agreement withR(t) but deviated visibly fromG (s) (t) at long times and/or high concentrations. Emission anisotropy measurements on glycerolic solutions of Na-fluorescein and rhodamine 6G were carried out at different excitation wavelengths. Very good agreement between the experimental data and the theory was found, with lambdaex~lambda0-0 for concentrations not exceeding 3.5.10(-2) and 7.5.10(-3) M in the case of Na fluorescein and rhodamine 6G, respectively. Up to these concentrations, the solutions investigated can be treated as one-component systems. The discrepancies observed at higher concentrations are caused by the presence of dimers. It was found that forlambda ex lambda0-0), they lie higher than the respective theoretical values. Such a dispersive character of the energy migration can be explained qualitatively by the presence of fluorescent centers with 0-0 transitions differing from the "mean" at lambda0-0. PMID- 24226908 TI - A statistical model of steady-state solvatochromism. AB - This work provides a description of the solvatochromic effect in terms of a hard sphere model taking into account the microscopic parameters of the solution. The average energies of the solute-solvent system were calculated for Franck-Condon and relaxed states assuming pairwise electrostatic interactions between polarizable, dipolar molecules contained in clusters made of 1-solute and 10 solvent molecules. This in turn allowed us to estimate the values of the solvatochromic shifts. The dependence of these shifts on temperature and electronic properties of molecules expressed in terms of their polarity and polarizability was investigated. PMID- 24226906 TI - Diapause, signal and molecular characteristics of overwintering Chilo suppressalis (Insecta: Lepidoptera: Pyralidae). AB - Diapause is a complex and dynamic process. Chilo suppressalis, an important rice pest in Asia enters facultative diapause as larvae. Our results demonstrated in Yangzhou, China, diapause was initiated between September 4 and 12, 2010. After diapause termination, C. suppressalis remained in quiescence in the field for as long as three months. The average time between collection of field larvae of C. suppressalis and their pupation decreased as the season progressed from fall to next spring. Unexpectedly, the pupated ratio of female to male in the initiation of diapause was 0.22. The abundance of hsp90, hsp70, hsp60 and CsAQP1 all peaked on January 8 or 15, 2011. Nitric oxide (NO) is a secondary messenger that is positively correlated with the diapause of C. suppressalis. Among several geographically separated populations of C. suppressalis, there are no significant differences in the mRNA levels of hsp70, hsp60 or CsAQP1. PMID- 24226909 TI - Accurate whole-spectrum measurements of intracellular pH and [Na(+)]. AB - Fluorescent measurements of intracellular H(+) and Na(+) are improved by using whole spectra of the fluorescent indicators BCECF and SBFI, respectively. The extra data in whole spectra enable both an accurate calibration and a ready detection of artifacts which are not possible to identify using a more conventional data analysis that relies upon only two wavelength "windows" in the fluorescence spectra. The whole-spectrum technique is applicable to cell suspensions in a conventional fluorimeter (as is reported here with SBFI), as well as to attached cells using a fluorimeter combined with an inverted epifluorescence microscope. The spectral method was highly reproducible in that pairs of successive pH measurements differed, on average, by only 0.01+/-0.02 U. Random uncertainty from sample to sample was estimated numerically from the standard deviation of measurements on ionophore-treated cells. When full-spectrum analysis was employed, this scatter showed a two-fold improvement over results obtained using the two-wavelength ratio method. Because SBFI has a relatively narrow dynamic range, whole-spectrum analysis has been applied to improve the accuracy of sodium determinations. The calibrated system measured [Na(+)]i with excellent linearity over the range 2-150 mM and with an accuracy of approximately 5 mM. PMID- 24226910 TI - Quantitative treatment of the effect of solvent on the electronic absorption and fluorescence spectra of substituted coumarins: Evaluation of the first excited singlet-state dipole moments. AB - The electronic absorption and fluorescence spectra of coumarin and 11 substituted coumarins were measured in several solvents (dioxane, ethyl ether, ethyl acetate, ethanol, dimethylformamide, acetonitrile, and dimethyl sulfoxide). Ground-state dipole moments were determined in dioxane at 298 K. The results were used to obtain the first excited singlet-state dipole moments of the coumarins under study by the solvatochromic shift method (Bakhshiev, Kawski-Chamma-Viallet, McRae, and Suppan correlations). Also, the ground- and the first excited singlet state dipole moments were calculated using a combination of the PPP method (pi contribution) and the vector sum of the sigma-bond and group moments (sigma contribution). In general, the first excited singlet-state dipole moments of the coumarins are noticeably higher than the corresponding ground-state values, indicating a substantial redistribution of thepi-electron densities resulting in a more polar excited state. There is a reasonably good agreement between the calculated and the experimental dipole moments. PMID- 24226911 TI - Time-resolved tryptophan fluorescence in flavodoxins. AB - The time-resolved fluorescence characteristics of tryptophan in flavodoxins isolated from the bacteriaDesulfovibrio gigas, Desulfovibrio vulgaris, Clostridium beijerinckii, andMegasphaera elsdenii were examined. The fluorescence decays were recorded using pulsed synchrotron radiation as the excitation source and time-correlated single-photon counting in detection. The results were analyzed as lifetime distributions using the maximum entropy method. Comparison of the fluorescence decays of normal and flavin mononucleotide-depleted flavodoxins demonstrates that radiationless energy transfer from tryptophan to flavin occurs in all flavodoxins investigated. On comparing the lifetime distribution patterns of apo and holoflavodoxins, it was noticed that a certain amount of apoprotein is present in all holoflavodoxin samples. The three dimensional structure of two flavodoxins allowed us to compare experimental with theoretical transfer rates and the results were in fair agreement. PMID- 24226912 TI - Myosin head rotation in muscle fibers measured using polarized fluorescence photobleaching recovery. AB - The technique of polarized fluorescence photobleaching recovery (PFPR) has been applied for the first time to investigation of the rotational correlation time of the myosin head in muscle fibers. This is a novel application of PFPR because it is the first time PFPR has been applied to a sample which is not cylindrically symmetric about the optical axis. Therefore we present a method for analysis of PFPR results from an oriented sample such as the muscle fibers aligned perpendicularly to the optical axis used here. Control experiments performed on fluorescently labeled myosin heads in solution demonstrate that, under some conditions, our PFPR apparatus can easily measure a rotational correlation time of less than 200 MUs. Validity of this application of PFPR to muscle fibers is provided by the agreement of our results with published results from a variety of other spectroscopic techniques. In particular, using glycerinated rabbit psoas muscle fibers, we find that for relaxed fibers and isometrically contracting fibers, the myosin heads undergo high-amplitude rotations on the submillisecond time domain. For fibers in rigor the myosin heads are highly oriented and nearly immobile. For fibers in ADP the myosin heads are highly ordered in a distribution quite different from that in rigor, and they are slightly more mobile than in rigor. PMID- 24226913 TI - Synthesis and spectroscopic studies of 4-Formyl-4'-N,N-dimethylamino-1,1' biphenyl: The unusual red edge effect and efficient laser generation. AB - The synthesis and photophysics of 4-formyl-4'-N,N-dimethylamino-1,1'-biphenyl are reported. The emission spectrum in various solvent polarities demonstrates solvatochromism, indicating that the fluorescence originates from an electronically excited species with a strong charge transfer character. The change in Delta[Formula: see text] [[Formula: see text] max(absorption) [Formula: see text] max(emission)] varies from ~1500 cm(-1) inn-heptane to as much as ~7500 cm(-1) in acetonitrile. In protic solvents, the unusual excitation energy-dependent steady-state emission (red edge effect), resulting from solvent dielectric relaxation, was observed in media with a low viscosity. The large Stokes-shifted and high-yield fluorescence led to the observation of the efficient lasing action. The frequency tunability of the laser output is strongly solvent dependent, generating a new charge transfer laser dye in the blue-green region. PMID- 24226914 TI - Electronic energy transfer in benzophenone adlayer. AB - The extent to which energy transfer occurs in electronically excited organic adlayer films on dielectric surfaces is investigated. Migration and subsequent trapping of the energy in the film are observed by pumping the singlet state of an organic adlayer of benzophenone and by monitoring the phosphorescence and fluorescence lifetimes. To observe the effects of adsorption, benzophenone was chosen as the adlayer because the energies of its well characterizedn,pi carbonyl states are remarkably sensitive to solvent interactions. Upon excitation with a nitrogen laser, the perturbation on the electronic states of benzophenone by the substrate caused the emergence of the normally absent fluorescence from the adlayer traps at the interface between the surface of the dielectric substrate and the adlayer. Energy transfer to this interface was observed as a function of film thickness. On the surface of a single crystal of an organic crystal, naphthalene, energy transfer from the adlayer to the substrate was observed, whereas such transfer was not energetically possible with the other dielectric surfaces. PMID- 24226915 TI - An ammonia-stabilized mixed-cation borohydride: synthesis, structure and thermal decomposition behavior. AB - We demonstrate the synthesis, crystal structure and thermal decomposition behavior of a novel ammonia-stabilized mixed-cation borohydride where the NH3 groups enable the coexistence of Li and Mg cations as an "assistant". Li2Mg(BH4)4.6NH3, which is comprised of orderly arranged Mg[NH3]6(2+) ammine complexes and Li2[BH4]4(2-) complex anions, was synthesized by the mechanochemical reaction between Mg(BH4)2.6NH3 and LiBH4. This novel compound crystallizes in a tetragonal P4(3)2(1)2 (No. 96) structure with lattice parameters a = b = 10.7656(8) A and c = 13.843(1) A with very short dihydrogen bonds, which determine a very low onset temperature of 80 degrees C for hydrogen release and are also responsible for the nucleation of Li2Mg(BH4)4.3NH3 as a decomposition intermediate. Mechanistic investigations on the thermal decomposition showed that the H(delta+)-H(delta-) combination in the ammonia stabilized mixed-cation borohydride was significantly enhanced due to the strengthened Mg-N bonds. Upon heating, 11.02 moles of H2 (equivalent to 11.1 wt%) and 3.07 moles of NH3 are evolved from one mole of Li2Mg(BH4)4.6NH3 with a three step reaction. The insights into the formation mechanism of ammonia-stabilized mixed-cation borohydride and the role played by NH3 group are very useful as a guideline for the design and synthesis of novel B-N-based materials with high hydrogen content. PMID- 24226916 TI - Pretreatment of urine samples with SDS improves direct identification of urinary tract pathogens with matrix-assisted laser desorption ionization-time of flight mass spectrometry. AB - We pretreated with SDS 71 urine samples with bacterial counts of >10(5) CFU/ml and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) identification scores of <2, in order to minimize failure rates. Identification improved in 46.5% of samples, remained unchanged in 49.3%, and worsened in 4.2%. The improvement was more evident for Gram-negative (54.3%) than for Gram-positive (32%) bacteria. PMID- 24226917 TI - Incorporation of a proteotyping approach using mass spectrometry for surveillance of influenza virus in cell-cultured strains. AB - The reemergence of deadly pandemic influenza virus strains has necessitated the development of improved methods for rapid detection and subtyping of influenza viruses that will enable more strains to be characterized at the molecular level. Representative circulating strains of human influenza viruses from primary clinical specimens were grown in cell culture, purified through polyethylene glycol precipitation, proteolytically digested with an endoproteinase, and analyzed and identified by high-resolution mass spectrometry using unique signature peptides that are characteristic of type A H1N1 and H3N2 and type B influenza viruses. This proteotyping approach enabled circulating strains of type A influenza virus to be typed and subtyped, cocirculating seasonal and pandemic H1N1 viruses to be differentiated, and the lineage of type B viruses to be determined through single-ion detection by high-resolution mass spectrometry. Results were obtained using virus titers comparable to those used in reverse transcription (RT)-PCR assays with clinical specimens grown in cell cultures. The methodology represents a more rapid and direct approach than RT-PCR and can be integrated into existing procedures currently used for the surveillance of emerging pandemic and seasonal influenza viruses. PMID- 24226918 TI - Rapid detection of Mycobacterium tuberculosis and pyrazinamide susceptibility related to pncA mutations in sputum specimens through an integrated gene-to protein function approach. AB - Testing the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis isolates is challenging. In a previous paper, we described the development of a rapid colorimetric test for the PZA susceptibility of M. tuberculosis by a PCR based in vitro-synthesized-pyrazinamidase (PZase) assay. Here, we present an integrated approach to detect M. tuberculosis and PZA susceptibility directly from sputum specimens. M. tuberculosis was detected first, using a novel long fragment quantitative real-time PCR (LF-qPCR), which amplified a fragment containing the whole pncA gene. Then, the positive amplicons were sequenced to find mutations in the pncA gene. For new mutations not found in the Tuberculosis Drug Resistance Mutation Database (www.tbdreamdb.com), the in vitro PZase assay was used to test the PZA resistance. This approach could detect M. tuberculosis within 3 h with a detection limit of 7.8 copies/reaction and report the PZA susceptibility within 2 days. In an initial testing of 213 sputum specimens, the LF-qPCR found 53 positive samples with 92% sensitivity and 97% specificity compared to the culture test for M. tuberculosis detection. DNA sequencing of the LF-qPCR amplicons revealed that 49 samples were PZA susceptible and 1 was PZA resistant. In the remaining 3 samples, with new pncA mutations, the in vitro PZase assay found that 1 was PZA susceptible and 2 were PZA resistant. This integrated approach provides a rapid, efficient, and relatively low-cost solution for detecting M. tuberculosis and PZA susceptibility without culture. PMID- 24226919 TI - Detection of Rickettsia in Rhipicephalus sanguineus ticks and Ctenocephalides felis fleas from southeastern Tunisia by reverse line blot assay. AB - Ticks (n = 663) and fleas (n = 470) collected from domestic animals from southeastern Tunisia were screened for Rickettsia infection using reverse line blot assay. Evidence of spotted fever group Rickettsia was obtained. We detected Rickettsia felis in fleas, Rickettsia massiliae Bar 29 and the Rickettsia conorii Israeli spotted fever strain in ticks, and Rickettsia conorii subsp. conorii and Rickettsia spp. in both arthropods. The sensitivity of the adopted technique allowed the identification of a new association between fleas and R. conorii subsp. conorii species. The presence of these vector-borne Rickettsia infections should be considered when diagnosing this disease in humans in Tunisia. PMID- 24226932 TI - Pinning effect for photoisomerization of a dicationic azobenzene derivative by anionic sites of the clay surface. AB - The photoisomerization behaviour of a dicationic azobenzene derivative on the inorganic surface was examined. The isomerization reaction was controlled by the charged array of the inorganic surface due to the "pinning effect" because of the electrostatic interaction between anionic charged sites on the inorganic surface and cationic charged sites in dye molecules. PMID- 24226924 TI - Comparison of Simplexa universal direct PCR with cytotoxicity assay for diagnosis of Clostridium difficile infection: performance, cost, and correlation with disease. AB - Simplexa Clostridium difficile universal direct PCR, a real-time PCR assay for the detection of the C. difficile toxin B (tcdB) gene using the 3M integrated cycler, was compared with a two-step algorithm which includes the C. Diff Chek-60 glutamate dehydrogenase (GDH) antigen assay followed by cytotoxin neutralization. Three hundred forty-two liquid or semisolid stools submitted for diagnostic C. difficile testing, 171 GDH antigen positive and 171 GDH antigen negative, were selected for the study. All samples were tested by the C. Diff Chek-60 GDH antigen assay, cytotoxin neutralization, and Simplexa direct PCR. Of 171 GDH positive samples, 4 were excluded (from patients on therapy or from whom duplicate samples were obtained) and 88 were determined to be true positives for toxigenic C. difficile. Of the 88, 67 (76.1%) were positive by the two-step method and 86 (97.7%) were positive by PCR. Seventy-nine were positive by the GDH antigen assay only. Of 171 GDH antigen-negative samples, none were positive by PCR. One antigen-negative sample positive by the cytotoxin assay only was deemed a false positive based on chart review. Simplexa C. difficile universal direct PCR was significantly more sensitive for detecting toxigenic C. difficile bacteria than cytotoxin neutralization (P = 0.0002). However, most PCR positive/cytotoxin-negative patients did not have clear C. difficile disease. The estimated cost avoidance provided by a more rapid molecular diagnosis was outweighed by the cost of isolating and treating PCR-positive/cytotoxin-negative patients. The costs, clinical consequences, and impact on nosocomial transmission of treating and/or isolating patients positive for toxigenic C. difficile by PCR but negative for in vivo toxin production merit further study. PMID- 24226933 TI - Magnetoresistive polyaniline/multi-walled carbon nanotube nanocomposites with negative permittivity. AB - Contrary to the observed positive giant magnetoresistance (GMR) in as-received multi-walled carbon nanotubes (MWNTs), pure polyaniline (PANI) synthesized with Cr(vi) as oxidant and MWNTs/PANI nanocomposites with ammonium persulfate (APS) as oxidant, a room temperature negative GMR of around -2% was reported in MWNTs/PANI nanocomposites with Cr(vi) as oxidant. Different from a frequency switch of permittivity from negative to positive in MWNTs/PANI nanocomposites with APS as oxidant, unique negative permittivity was observed in MWNTs/PANI nanocomposites with Cr(vi) as oxidant within the measured frequency range from 20 to 2 * 10(6) Hz. The obtained unique negative permittivity was explained by the plasma frequency from the Drude model, at which the permittivity changes from negative to positive and the material changes from a metamaterial to an ordinary dielectric medium. The observed positive and negative GMR behaviors in these disordered systems as verified by the temperature dependent resistivity exploration were well explained through a wave-function shrinkage model and orbital magnetoconductivity theory by calculating the changed localization length (a0). PMID- 24226934 TI - Trapped in misbelief for almost 40 years: selective synthesis of the four stereoisomers of mefloquine. AB - Here we report the synthesis of all four stereoisomers of mefloquine. Mefloquine (Lariam) is an important anti-malaria drug that is applied as a racemate of the erythro form. However, the (-)-isomer induces psychosis, while the (+)-enantiomer does not have this undesired side effect. There are six syntheses of which five lead to the wrong enantiomer without the authors of these syntheses noting that they had synthesized the wrong compound. At the same time physical chemistry investigations had assigned the absolute configuration correctly and the last enantioselective synthesis that took these results into account delivered the correct absolute configuration. Since various synthetic approaches failed to provide the correct stereoisomers in previous syntheses, we submit here a synthetic approach with a domino Sonogashira-6pi-electrocyclisation as key step that confirmed synthetically the correct absolute configuration of all four isomers. PMID- 24226936 TI - Genetic transformation of strawberry by Agrobacterium tumefaciens using a leaf disk regeneration system. AB - An efficient genetic transformation protocol has been developed for strawberry cv. Redcoat using Agrobacterium tumefadens. The protocol relies on a high frequency (84%) shoot regeneration system from leaf disks. The leaf disks were inoculated with a non-oncogenic Agrobacterium tumefadens strain MP90 carrying a binary vector plasmid pBI121 which contains a chimeric nopaline synthase (NOS) promoter driven neomycin phosphotransferase (NPT II) gene and a cauliflower mosaic virus 35S (CaMV35S) promoter driven, beta-glucuronidase (GUS) marker gene. The inoculated leaf disks, pre-cultured for 10 days on non-selective shoot regeneration medium, formed light green meristematic regions on selection medium containing 50 MUg/ml kanamycin. These meristematic regions developed into transformed shoots at a frequency of 6.5% on a second selection medium containing 25 MUg/ml kanamycin. The selected shoots were multiplied on shoot proliferation medium in the presence of kanamycin. All such shoots were resistant to kanamycin and expressed varying levels of NPT II and GUS enzyme activity. Histochemical assays for GUS activity indicated that the 35S promoter was highly active in meristematic cells of shoot and root apices. Molecular analysis of each transgenic clone confirmed the integration of both marker genes into the strawberry genome. Leaf disks prepared from transformed plants, when put through the second selection cycle on kanamycin, formed callus and exhibited GUS activity. The rooted transformed plants were grown in a greenhouse for further characterization. The protocol may be useful for improvement of strawberry through gene manipulations. PMID- 24226935 TI - The influence of type-specific human papillomavirus infections on the detection of cervical precancer and cancer: A population-based study of opportunistic cervical screening in the United States. AB - There are limited data on the prospective risks of detecting cervical precancer and cancer in United States (US) populations specifically where the delivery of opportunistic cervical screening takes place outside managed care and in the absence of organized national programs. Such data will inform the management of women with positive screening results before and after widespread human papillomavirus (HPV) vaccination and establishes a baseline preceding recent changes in US cervical cancer screening guidelines. Using data reported to the statewide passive surveillance systems of the New Mexico HPV Pap Registry, we measured the 3-year HPV type-specific cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 or more severe (CIN3+) detected during real-world health care delivery across a diversity of organizations, payers, clinical settings, providers and patients. A stratified sample of 47,541 cervical cytology specimens from a screening population of 379,000 women underwent HPV genotyping. Three-year risks for different combinations of cytologic interpretation and HPV risk group ranged from <1% (for several combinations) to approximately 70% for CIN2+ and 55% for CIN3+ in women with high-grade (HSIL) cytology and HPV16 infection. A substantial proportion of CIN2+ (35.7%) and CIN3+ (30.9%) were diagnosed following negative cytology, of which 62.3 and 78.2%, respectively, were high-risk HPV positive. HPV16 had the greatest 3-year risks (10.9% for CIN2+,8.0% for CIN3+) followed by HPV33, HPV31, and HPV18. Positive results for high-risk HPV, especially HPV16, the severity of cytologic interpretation, and age contribute independently to the risks of CIN2+ and CIN3+. PMID- 24226937 TI - Transient expression of the beta-glucuronidase gene introduced into barley coleoptile cells by microinjection. AB - A beta-glucuronidase gene was introduced directly into barley (Hordeum vulgare L. cv. Kobinkatagi) coleoptile cells by microinjection and transient expression of the gene was examined. Inner epidermis tissue of coleoptiles was excised and injected with plasmid DNA, pBI221, carrying cauliflower mosaic virus 35S promoter, beta-glucuronidase gene, and a nopaline synthase polyadenylation region. Histochemical assay for beta-glucuronidase production showed positive enzyme activity only in coleoptile cells injected with plasmid DNA. Expression of the beta-glucuronidase gene was examined chronologically using honogenates of injected coleoptile tissues. Glucuronidase activity first appeared after 6 hr, reached the maximum level 24 hr after injection, and decreased afterwards. These results suggest that microinjection of coleoptile tissues may be a useful approach for the genetic engineering of Gramineae plants in which protoplast regeneration is difficult. PMID- 24226938 TI - Transformation of cultured cells of Chenopodium quinoa by binary vectors that carry a fragment of DNA from the virulence region of pTiBo542. AB - A 15.2-kb KpnI fragment from the virulence region of pTiBo542, the Ti plasmid harbored by Agrobacterium tumefaciens strain A281, was introduced into binary vectors. The fragment contained the virB, virC and virG genes, and it is known to have the ability to increase the virulence of strains of A. tumefaciens. The strains of A. tumefaciens that carried the resulting plasmids were able to transform cells in a suspension culture of Chenopodium quinoa Willd cells which were not transformable by common vectors. Although the sizes of the plasmids was very large, a foreign segment of DNA was introduced into one of the plasmids by homologous recombination in A. tumefaciens cells, and the segment was subsequently transferred to plant cells. PMID- 24226939 TI - Lobeline production by hairy root culture of Lobelia inflata L. AB - Hairy roots were obtained following inoculation of the stems of Lobelia inflata L. with Agrobacterium rhizogenes strain ATCC 15834. These hairy roots contained agropine and mannopine. In addition, lobeline was detected by HPLC and confirmed by mass spectrometry. Various media were tested for the growth of hairy roots as well as for the content of lobeline in hairy roots. The growth rate of hairy roots cultured in Nitsch and Nitsch's medium was approximately one third of those cultured in other media. The lobeline content of hairy roots (18-54 MUg/g dry weight) cultured in these media was the same order of magnitude compared with that of roots of L. inflata (24 MUg/g dry weight) cultivated in pots. The hairy roots cultured in Nitsch and Nitsch's medium were morphologically different from those cultured in other media. PMID- 24226940 TI - Efficient plant regeneration from hypocotyl protoplasts of broccoli (Brassica oleracea L. ssp. italica Plenck). AB - We have assessed the capacity of cultured protoplasts from two tissue sources of several commercially-grown broccoli cultivars to regenerate plants. A procedure that employs hypocotyl protoplasts and a culture medium with a high NAA:2,4-D auxin ratio was developed. The procedure permits highly efficient formation of colonies that regenerate shoots at frequencies of 8-17% with two of the four cultivars tested. The time required for the development of plants from protoplasts was 8-11 weeks. No mtDNA rearrangements were observed among any of 17 analysed regenerants. Double-stranded RNAs were detected in mitochondrial DNA (mtDNA) preparations of some, but not all, regenerants of one of the cultivars. PMID- 24226941 TI - A simple, versatile feeder layer system for Brassica oleracea protoplast culture. AB - Protoplasts from cauliflower (Brassica oleracea ssp. botrytis) and broccoli (ssp. italica) leaves and hypocotyls were successfully cultured on membrane filters over a feeder layer of cells from a B. campestris suspension culture. Cells from rice, tomato and tobacco suspensions were not as effective as the B. campestris cells. Plants were recovered from protoplasts of previously recalcitrant Brassica genotypes. Protoplasts cultured in low numbers (10-100) on the feeder layer divided and formed colonies capable of plant regeneration, as did fused protoplasts. PMID- 24226942 TI - Somatic embryogenesis and plant regeneration from immature zygotic embryos of papaya (Carica papaya L.). AB - Immature zygotic embryos from open-pollinated and selfed Carica papaya L. fruits, 90 to 114 days post-anthesis, produced 2 to 20 somatic embryos on apical domes, cotyledonary nodes, and radicle meristems after culture for three weeks on half strength Murashige and Skoog (MS) medium supplemented with 0.1 to 25 mg l(-1) 2,4 dichlorophenoxyacetic acid (2,4-D), 400 mg l(-1) glutamine, and 6% sucrose. After six weeks of culture, about 40 to 50% of the zygotic embryos had become embryogenic, and each embryogenic embryo yielded hundreds of somatic embryos within five months of culture on media supplemented with 2,4-D. Somatic embryos matured on half-strength MS medium, germinated on MS medium containing 5 mg l(-1) kinetin, and grew large enough for greenhouse culture on MS medium. Shoots were rooted in vermiculite and grown in the greenhouse. PMID- 24226943 TI - Glucosylation of salicylic acid by cell suspension cultures of Mallotus japonicus. AB - Salicylic acid was converted into its O-glucoside when administered to cell suspension cultures of Mallotus japonicus. The efficiency of the glucosylation was highest in the cells grown in Linsmaier-Skoog medium containing 1 MUM 2,4 dichlorophenoxy-acetic acid at any scale of culture (7 ml - 3 1). The yield of salicylic acid-O-glucoside could be increased up to 1.1 g/l by continuously dripping a non-toxic amount of salicylic acid (5.8 mg/31 medium/h) to a 51 fermenter during a culture period of 14 d. PMID- 24226944 TI - Cryopreservation of dried axillary buds from plantlets of Asparagus officinalis L. grown in vitro. AB - Dried axillary buds from plantlets of Asparagus lofficinalis L. grown in vitro were successfully cryopreserved. Single node segments (5mm in length) with axillary bud were taken from mature in vitro plantlets. The segments were precultured on solidfied Murashige-Skoog medium (1962) containing 0.7M sucrose at 25 degrees C in light for 2 days. Thereafter, these precultured segments were subjected to dehydration with silica gel at room temperature for 0 to 24 h. The axillary buds of precultured segments tolerated dehydration to about 14% water content(FW) with 50% lethality (LD50) and the threshold water content at which the dried buds remained alive after exposure to liquid nitrogen was 16.9%(LD50). The maximum rate of survival of cryopreserved buds was about 71% of untreated control. Surviving buds produced shoots and regenerated into plantlets. These results demonstrate the feasibility of cryopreserving dried axillary buds from in vitro plantlets. PMID- 24226945 TI - Botanical and chemical evaluation of Atractylodes lancea plants propagated in vitro and by division of the rhizome. AB - A single plant of Atractylodes lancea, a perennial herb of Asteraceae, was propagated in vitro by shoot culture from floral buds and shoot tips. The reproduced plants were then grown under field conditions for up to four years and their botanical and chemical characteristics were compared to those of control plants that were propagated by dividing the rhizome of the parent plant. The first-year-plants of the micropropagated plants were scanty, but in the second year they were comparable to the control in most botanical features. On the other hand, the contents of two sesquiterpenes (hinesol and beta-eudesmol) and a polyacetylenic compound (atractylodin) in the rhizome of the micropropagated plants remained low for the first two or three years of cultivation and at the third or fourth year they reached to the same level as that of the control. Accordingly micropropagation yields clonal plants of A. lancea comparable to those obtained by conventional propagation methods within three or four years of cultivation. PMID- 24226946 TI - Factors affecting PEG-mediated stable transformation of maize protoplasts. AB - Factors influencing the frequency of stable transformation and co-transformation of maize protoplasts utilizing a polyethylene glycol (PEG) mediated DNA uptake procedure have been investigated. Protoplast plating conditions, pre-treatment buffer composition, PEG concentration, and DNA concentration were all found to be important. Carrier DNA was not beneficial when transforming with circular plasmid DNA. The effect of linearizing plasmid DNA was inconsistent across experiments, and may be dependent on the presence of carrier DNA. Functional co-transformation of an unlinked marker gene (hygromycin phosphotransferase) was increased by increasing the ratio of nonselected:selected DNA, and varied from 39% at a 1?1 ratio to 65% at a 100?1 ratio. Under optimum conditions, up to 300 transformed calli were recovered per million input protoplasts. The protocol is simple, inexpensive, and effective, and is useful for studies in maize requiring large numbers of stably transformed or co-transformed cell lines. PMID- 24226947 TI - Isolation and culture of protoplasts from embryogenic suspension cultures of red fescue (Festuca rubva L.). AB - Protoplasts were isolated from fast-growing embryogenic suspension cultures of red fescue cv. Dawson (Festuca rubra L.) without agitation. The enzyme isolation solution was highly efficient at releasing protoplasts of greater than 95% viability (5*10(6)-10(7) protoplasts per ml of packed cell volume). A three step procedure was followed for washing and transferring protoplasts from a solution high in inorganic salts to a medium containing glucose and sucrose. The addition of 30 mM sodium thiosulfate to the wash and culture media was found to be helpful in reducing the number of lysed protoplasts. Isolated protoplasts began to divide within 48-72 h when protoplasts were plated in agarose squares and surrounded by nurse cells (mixed nurse plating technique). Maximum colony formation (plating efficiency) was approximately 1%. Many of the colonies continued to grow and produced embryos when transferred to a medium consisting of half-strength MS salts, 4 mg/l 2,4-D, 3 g/l casein hydrolysate and 30 g/l sucrose. Upon transfer to hormone-free medium and exposure to light 16 h/day, many of the embryos germinated to produce green leaves and roots. PMID- 24226948 TI - Plant regeneration capacity of callus derived from leaf, stem, and root segments of Populus alba L. x P. grandidentata Michx. AB - Expiants for establishing callus cultures originated from in vitro cultured hybrid poplar (Populus alba L. X P. grandidentata Michx.). Plant regeneration was achieved from established callus cultures derived from stem internodes (SI), leaf discs (LD), and root segments (RS). Shoot regeneration from callus occurred within 4 weeks of culture on most of the media tested. Frequency of shoot formation was greatly increased by subculturing the selected organogenic calli on regeneration media. The highest rate of multiple shoot formation (an average number of 7/SI, 11/LD, and 8/RS) was obtained by using 0.05 MUM IBA in combination with 22.5 MUM 2iP, 22.5 MUM zeatin, and 12.5 MUM 2iP, respectively. Regenerated shoots were easily rooted in polyterra(TM) peat plugs in transparent plastic boxes. The rooted plantlets were subsequently transferred to pots containing an artificial potting mix. PMID- 24226949 TI - Erratum. PMID- 24226950 TI - A new system to bioassay pesticides present in the surface microlayer using floating propagules of an aero-aquatic hyphomycetous fungus Pseu doaegerita matsushimae. AB - The surface microlayer often contains pesticides at levels which may be more than one hundred thousand times those sampled in the remainder of the water column. Standard bioassay systems cannot asses these pesticides since no system yet devised has made use of organisms inhabiting the surface microlayer. Using floating propagules of Pseudoaegerita matsushimae, an aeroaquatic hyphomycetous fungus, a bioassay system was devised in which the percentage germinations of such propagules after exposure to various levels of pesticides were plotted to produce a dosegermination scale onto which subsequent data could be fitted. The following pesticides and pesticide mixtures were used: PCP; DDT; Methoxychlor; Bis(tributyl)tin Oxide; Malathion; Captan; 1 part PCP/1 part DDT; 2 parts PCP/1 part DDT; 3 parts PCP/1 part DDT; 2 parts DDT/1 part PCP; 3 parts DDT/1 part PCP; 1 part PCP/1 part Methoxychlor; 2 parts PCP/1 part Methoxychlor; 3 parts PCP/1 part Methoxychlor; 2 parts Methoxychlor/1 part PCP; 3 parts Methoxychlor/1 part PCP. The bioassay system revealed increased sensitivity to pesticides and pesticide mixtures which affected respiratory metabolism. Some pesticide mixtures were more effective in inhibiting germination than their individual components while others appeared much less toxic to the propagules than their unassisted components. PMID- 24226951 TI - Mercury bioaccumulation in organisms from three Puerto Rican estuaries. AB - We analyzed mercury levels in shrimp (Palaemonetes sp.), Blue Crabs (Callinectes sp.), fish (Tarpon Megalops atlantica and Tilapia Tilapia mossambica), lizards (Ameiva exsul), Cattle Egret (Bubulcus ibis) and Moorhen (Gallinula chloropus) in three estuaries in Puerto Rico in 1988. There were no quantifiable concentrations greater than the method detection limit of mercury in shrimp, crabs and lizards from any site. Mercury levels were also below detection limits in Tilapia, except for specimens collected at Frontera Creek, allegedly contaminated with mercury. However, mercury levels ranged from 92-238 MUg/kg (wet weight) in Tarpon, a predaceous fish that feeds on smaller fish. Few of the birds had detectable levels of mercury. Our results indicate relatively low concentrations of mercury in biota collected in all of the three estuaries at most trophic levels, although 10 of 12 Tarpon fillet samples from Frontera had detectable mercury compared to 3 of 12 fillet samples for the other two lagoons. PMID- 24226952 TI - COD and TOC analysis of leachate from a solidified organic waste. AB - Several combinations of binders and absorbent additives were utilized to solidify a typical organic waste, API Separator sludge. The effectiveness of the materials was based on the waste leachability from the solidified samples. COD and TOC analyses were used to determine the organic content of the leachate samples.The ability of the COD and TOC analyses to assess waste leachability was limited. The inability of the COD and TOC tests to differentiate between organic compounds made the results difficult to interpret. This was due to organic contaminants from the solidification materials contributing to the COD and TOC contents of the leachates. Also, the COD test may have be influenced by reduced inorganic compounds contained in the flyash binder and the sludge. Representative samples for the TOC analysis were difficult to obtain for the leachates containing oils or suspended particles. It is recommended that the COD and TOC tests only be used as a screening method for determining solidified organic waste leachability and other methods need to be employed to obtain more accurate results. PMID- 24226953 TI - An environmental stress information system. AB - This paper reports on the development of an environmental stress information system (ESIS) for the purpose of storing, updating and analysing environmental stress data related to noise, heat, improper illumination and air contaminants. The information system (ESIS) consists of a set of programs as well as a set of data base files for the purpose of efficient data processing. The system is user friendly and, once started, guides the user with the help of menu-driven options. All data related to noise, heat, illumination and air contaminants can be entered, updated, displayed or printed in certain specified formats. Finally, the use of the ESIS in evaluating air contaminants such as total suspended particles, certain specified metals and inorganic gases in the Jeddah Industrial estate is also reported. PMID- 24226954 TI - Riverine pollution in some northern and north eastern states of india. AB - Water samples from 30 rivers in northern and north-eastern hilly states of India were analysed for bacteriological and physicochemical parameters along with metals and pesticide residues. It was found that 34% of samples had >50 coliforms/100 ml, while 24% of samples demonstrated >50 thermotolerant (faecal) coliforms/100 ml. Among the metals, iron was found to be above maximum permissible limits in the rivers of all the states, while manganese was found to be above the maximum permissible limit in the rivers of Tripura and some northern states. Zinc, lead, nickel, chromium, copper, cobalt and cadmium plus physicochemical parameters and residual pesticides, however, were within their maximum permissible limits. PMID- 24226955 TI - Distribution of suspended particulate matter with trace element composition and apportionment of possible sources in the Raniganj coalfield, India. AB - Ambient air monitoring for suspended particulate matter was carried over a period of one year in some coal mining areas of the Raniganj coalfield. Concentrations of seven elements in suspended particulate matter were determined. The set of data obtained was analysed to determine the sources of trace elements by factor analysis. The data could be interpreted on the basis of five factors. These factors are attributed to various sources of particulate matter by noting the dependence of factors on the elements. PMID- 24226956 TI - Innate lymphoid cells: new players in atherosclerosis? PMID- 24226957 TI - Notice of retraction. PMID- 24226961 TI - Effects of desiccation and rehydration on nitrogen fixation by epiphylls in a tropical rainforest. AB - Nitrogen fixation rates by epiphyllous microorganisms are affected by desiccation. Rates from leaf samples which had been dried for 12 h were 0.66 ng N/10 cm(2)/h. In contrast, rates from leaves which had been kept continuously wet were 18.69 ng N/10 cm(2)/h. Leaf samples which had been rehydrated for 2 and 4 h showed intermediate fixation rates (4.26 and 9.76 ng N/10 cm(2)/h, respectively). Epiphyllous bryophytes maintain moist conditions on the leaf surface and thus create a microenvironment suitable for prolonged fixation by the microorganisms. PMID- 24226960 TI - Nitrogen economy of endolithic microbial communities in hot and cold deserts. AB - The source of combined nitrogen in endolithic microbial communities was studied in samples from desert localities in North and South America, the Middle East, South Africa, and Antarctica. Nitrogen fixation (acetylene reduction) seems to occur only exceptionally. Evidence suggests that, in general, the nitrogen source for endolithic microorganisms in deserts is abiotically fixed nitrogen produced by atmospheric electric discharges (lightning or aurorae), conveyed to the rock by atmospheric precipitation. Nitrogen is apparently not a limiting factor in these low-productivity communities. An incomplete nitrogen cycle seems to be present which includes the following pathways: supply of nitrates and ammonia from the atmosphere; decomposition of organic matter to ammonia; reassimilation of ammonia; ammonia volatilization; loss of organic matter through weathering (only in certain Antarctic rocks); biological nitrogen fixation (exceptional). PMID- 24226962 TI - Effects of water fluctuations on microbial mass and activity in soil. AB - When previously dried soil was remoistened, a series of microbial events occurred. The bacterial plate count population increased rapidly, with a doubling time of 4-5 h. The length of fungal hyphae and microscopic counts of bacteria increased more slowly. The microscopically counted bacterial population was estimated to have a doubling time of about 90 h. The respiratory burst occurring after 2-3 days coincided with the maximal growth rate of the bacterial plate count population. From the respiratory data, plate count bacteria were estimated to have a cell mass of 0.4 pg dry weight, whereas the mass of microscopically counted bacteria was only 10% of this. Changes in bacterial DNA content corresponded to changes in the microscopic count, whereas changes in soil catalase activity mainly corresponded to changes in the fungal biomass, which was dominant.It is suggested that bacterial plate counts and microscopic counts represent two distinct populations of bacteria, which for practical purposes may be termed zymogenous and autochthonous, respectively. PMID- 24226963 TI - Characterization, distribution, and significance ofMetallogenium in Lake Washington. AB - During summer stratification,Metallogenium personatun was found exclusively in the hypolimnion of Lake Washington where the oxygen tension was below 8 ppm. Numbers of the organism decreased in the lake immediately following turnover in October. Significant concentrations ofMetallogenium microcolonies did not recur until spring, after the lake had stratified. During stratification the distribution of particulate manganese closely followed the distribution ofMetallogenium. EDAX analysis, confirmed by electron microprobe analyses of the encrustation, showed that the primary component was manganese. Iron and some trace elements were also precipitated on the organism but to a lesser degree. In addition, phosphate, the primary substance limiting phytoplankton growth in Lake Washington, was found in the encrustation, indicatingMetallogenium maybe important in limiting algal blooms in the lake. Attempts to growMetallogenium in the laboratory were unsuccessful. This inability, combined with the negative results of thin-sectioning and acridine orange staining ofMetallogenium microcolonies, suggests that the microcolonial structures seen in Lake Washington are not a living form of an organism. PMID- 24226964 TI - DNA base compositions of halophilic and nonhalophilicBacillus firmus strains of marine origin. AB - The mineral salt requirements of 27 strains ofBacillus firmus were determined. Twenty-six of these strains were of marine origin and one terrestrial strain was used as a reference. Three strains demonstrated strictly halophilic behavior, i.e., they showed no growth in media prepared without sodium chloride. Seven strains were nonhalophilic. The growth of 17 strains was stimulated by the addition of sodium chloride, but the cells were able to grow without it. These results were compared with the DNA base compositions of the strains. In contrast to literature data, relationships between the DNA base ratios and the halophilic or nonhalophilic behavior of the cells could not be detected. But strains with guanine plus cytosine values above 41 mol% did grow well at 44 degrees C, and those strains showing poor growth at this temperature had lower guanine plus cytosine percentages. PMID- 24226965 TI - Chemotactic responses ofThiobacillus thioparus. AB - A capillary assay was employed to quantify chemotactic responses in the chemoautotrophic bacterium,Thiobacillus thioparus. NH4Cl, KNO3, and Na2S2O3 were strong attractants. The minimum concentration of each of these inorganic chemicals needed to elicit an observable response was approximately 10(-4) M.T. thioparus did not respond to carbohydrates or amino acids. PMID- 24226966 TI - Effect of food level on reproduction and metamorphosis in the suctorian protozoanTokophrya lemnarum stein. AB - A sessile predator, the ciliated protozoanTokophrya lemnarum, produces a motile embryo. The embryo attaches to a substrate and secretes a stalk at metamorphosis. Production of the offspring is closely synchronized with the feeding schedule, so that fecundity per individual varies directly with the food level. Some embryos produced by an adult do not attach at metamorphosis but become freely floating adults. The percentage of nonattaching embryos is compared between adults fed high or low level diets. Adults on the low level diet produce 25% or more nonattaching embryos compared to 10% or less produced by adults on a high level diet. If the adult is switched from a low level diet to a high level diet, or from high to low, the percentage of nonattaching embryos produced on each diet remains relatively constant. It is suggested that nonattachment provides one means for individuals to escape areas of low prey density and availability. PMID- 24226967 TI - Physiological ecology of acetylene reduction (nitrogen fixation) in a Delaware salt marsh. AB - The effects of several fixed nitrogen compounds on acetylene reduction activity (nitrogen fixation) of surface sediments from a Delaware salt marsh were studied. Ammonia addition caused little decrease in activity early in the summer but resulted in a considerable decrease (85-95%) in activity late in the summer and early in the fall. Nitrate caused a near complete suppression of activity at all times. Other compounds such as glutamate, urea, and yeast extract caused a slight increase in activity in tallSpartina sediments and caused more than a 2.5-fold increase in shortSpartina sediments. There was a lag period (1-2 days) before the commencement of in vitro acetylene reduction activity during the spring and early summer, but this lag period was not present in the late summer. The addition of chloramphenicol to samples from a shortSpartina zone caused decreases in activity similar to those obtained with ammonia, whereas chlorate amendments yielded results which, when compared on an electron basis, were comparable to those obtained with nitrate. These results indicated that the observed lag period may be the result of a physiological response to the in situ levels of ammonia and/or nitrate. It is suggested here that in situ nitrogenase activity may be controlled by two processes: (a) repression and derepression of nitrogenase synthesis mediated by the levels of ammonia, and (b) competition for reducing power (electrons) and energy (ATP) between the processes of nitrate reduction and nitrogen fixation. PMID- 24226968 TI - Toxicity of carbide waste to heterotrophic microorganisms in caves. AB - The spent carbide from acetylene-generating lamps used by spelunkers has long been assumed to be toxic. Pure cultures ofE. coli, S. cerevisiae, andB. subtilis were inhibited within 15 minutes by addition of a 1% solution of waste carbide. The heterotrophic microorganisms which form the food base in caves were depressed 81% in 1 hour by the application of fresh carbide waste to a cave stream mudbank. The effects were temporary as the toxicity was lost when the extremely alkaline pH of the waste was neutralized. The reduction in pH occurs naturally over time by atmospheric and substrate buffering and is probably related to soil type and available moisture. PMID- 24226969 TI - A method of the selective isolation and enumeration of marine Vibrionaceae. AB - A noninhibitory medium and GasPack anaerobic culture system were employed for the selective enumeration and isolation of Vibrionaceae in seawater and marine sediments.Vibrio counts obtained by the new method for seawater and sediment samples were compared with vibrio numbers in the heterotrophic bacterial population appearing on a medium routinely employed in the laboratory for such counts. The ratio of the former to the latter counts ranged from 0.5 to 1.3, the average being 0.96. The seawater and sediment bacteria that grew and produced visible colonies on the medium under anaerobic conditions for 3 days at 20 degrees C were almost exclusively vibrios.From the results reported here it is concluded that most of the vibrios present in seawater and sediment samples can be recovered by the new method developed in this study. PMID- 24226970 TI - Prediction of obstetrical risk using maternal serum markers and clinical risk factors. AB - OBJECTIVE: Abnormal maternal serum analytes (pregnancy associated plasma protein A, total human chorionic gonadotropin, alpha fetoprotein, Inhibin A, and unconjugated estriol) measured as part of aneuploidy screening programs have been associated with adverse obstetrical outcomes in euploid pregnancies. This study aimed to determine if their predictive ability could be enhanced with additional information on obstetrical history. METHOD: Forty-five thousand two hundred eighty-seven women participated in the screening program and delivered euploid singleton infants between 2010 and 2012 in British Columbia, Canada. A split sample design was used to develop and validate prognostic models for serious perinatal events (stillbirth, preterm birth <32 weeks, or HELLP syndrome) and severe pre-eclampsia [pre-eclampsia with preterm birth <34 weeks or small for gestational age <10th percentile] using logistic regression. RESULTS: Three thousand five hundred four women (7.7%) had at least one abnormal marker using standard cut-off values. The combination of serum markers and clinical risk factors improved the ability of statistical models to predict a serious perinatal event [area under the curve (AUC) = 0.62] and severe pre-eclampsia (AUC = 0.78) compared with serum markers or clinical risk factors alone. CONCLUSIONS: While detection rates are low, the combination of maternal serum markers and obstetrical history helps to identify a small subset of women at higher risk for serious perinatal events and severe pre-eclampsia. PMID- 24226971 TI - [Model aeroplanes: a not to be ignored source of complex injuries]. AB - With the incidence of work-related injuries decreasing, we continue to observe an unchanged trend in leisure-related accidents. As in any other hobby, model flying devices bear the risk for accidents among builders and flyers ranging from skin lacerations to complicated and even life-threatening injuries. The fast-moving razor-sharp propeller blades predominantly cause trauma to the hands and fingers resulting in typical multiple parallel skin injuries also affecting structures deep to the dermis (e. g., tendons, vessels and nerves). The resultant clinical management involves complex reconstructive surgical procedures and prolonged rehabilitative follow-up. Improving the legal framework (e. g., warnings by the manufacturer) on the one hand, providing informative action and sensitising those affected on the other, should form a basis for an altered prevention strategy to reduce model flying device-related injuries in the future. PMID- 24226972 TI - Fast presurgical magnetic resonance imaging of meniscal tears and concurrent subchondral bone marrow lesions. Study of dogs with naturally occurring cranial cruciate ligament rupture. AB - Meniscal tears and subchondral bone marrow lesions have both been described in dogs with cranial cruciate ligament rupture, but their possible concurrence has not been evaluated. In a population of 14 dogs exhibiting signs of stifle pain with surgically confirmed cranial cruciate ligament rupture, a short presurgical 1.5T magnetic resonance (MR) imaging protocol including dorsal proton density, dorsal T1-weighted gradient recalled echo, and sagittal fat-saturated dual echo sequences was tested to further investigate these features and illustrate meniscal tears. Interobserver agreement for detection of medial meniscal tears (k=0.83) and bone marrow lesions (k=0.87) was excellent. Consensus MR reading allowed detection of nine out of 12 surgically confirmed medial meniscal tears and there was no false positive. All dogs had cruciate ligament enthesis-related bone marrow lesions in the tibia, femur or both bones. Additionally, among the 12 dogs with confirmed medial meniscal tears, subchondral bone marrow lesions were present in the caudomedial (9 dogs) and caudoaxial (11 dogs) regions of the tibial plateau, resulting in odds ratios (13.6, p=0.12, and 38.3, p=0.04, respectively) that had large confidence intervals due to the small group size of this study. The other two dogs had neither tibial bone marrow lesions in these locations nor medial meniscal tears. These encouraging preliminary results warrant further investigation using this clinically realistic preoperative MR protocol. As direct diagnosis of meniscal tears remained challenging in dogs even with high-field MR, identification of associated signs such as subchondral bone marrow lesions might indirectly allow suspicion of an otherwise unrecognized meniscal tear. PMID- 24226973 TI - Steroidogenesis during induced oocyte maturation and ovulation in the African catfish,Clarias gariepinus. AB - Changes in ovarian steroidogenesis accompanying oocyte maturation and ovulation were studied in the African catfish,Clarias gariepinus. Laboratory-reared females with postvitellogenic ovaries were treated with pimozide and LHRH-analogue. The plasma gonadotropin levels were determined by means of a homologous radioimmunoassay, the condition of the ovaries was studied by histological examination of the follicles, and the steroidogenetic capacity of the ovaries was analyzed byin vitro incubation of tissue fragments for 3 h with [(3)H] pregnenolone and [(3)H]androstenedione as precursors. Data were collected at regular intervals between 0 and 16 h after pimozide-LHRH analogue administration.Until 4 h after the beginning of the experiments the plasma gonadotropin levels did not rise above 25 ng/ml, the ovaries remained in the stage of postvitellogenesis, and testosterone was the main end product of steroidogenesis. Four hours later the gonadotropin concentration in the blood had risen to more than 150 ng/ml, and the ovaries had entered the stage of germinal vesicle migration. At the same time steroidogenesis shifted towards the production of 17alpha,20beta-dihydroxy-4-pregnen-3-one, 5beta-pregnane-3alpha, 17alpha-diol-20-one, 5beta-pregnane-3alpha,6alpha,17alpha-triol-20-one, 5beta pregnane-3alpha,17alpha,20beta-triol and 5beta-pregnane 3alpha,6alpha,17alpha,20beta-tetrol. During the subsequent stage of germinal vesicle breakdown the plasma gonadotropin level remained high, and the synthesis of the C21-steroids showed a further increase. Simultaneously, the production of some C19-steroid glucuronides was enhanced. The preovulation and especially the postovulation stages were accompanied by a gradual decrease in steroidogenic capacity of the ovaries, even though the plasma gonadotropin level remained high. It is concluded that the prematuration surge of gonadotropin influences the activity of enzymes involved in steroidogenesis, leading to a reduced C17,20 lyase and to an augmented activity of the enzymes 20beta-hydroxysteroid dehydrogenase (HSD), 5beta-reductase, 3alpha-HSD, 6alpha-hydroxylase and UDP glucuronosyltransferase. During ovulation the activity of all steroidogenic enzymes, including such key enzymes as 3beta-HSD and 17alpha-hydroxylase, gradually decreases.Not only 17alpha,20beta-dihydroxy-4-pregnen-3-one, but also the 5beta-reduced pregnanes may be involved in inducing oocyte maturation and/or ovulation. The very polar triol and tetrol products may function, together with the steroid glucuronides as sex pheromones. PMID- 24226974 TI - Plasma profiles of fourteen ovarian steroids before, during and after ovulation in African catfish,Clarias gariepinus, determined by gas chromatography and mass spectrometry. AB - The plasma concentrations of fourteen ovarian steroids were measured in postvitellogenic African catfish,Clarias gariepinus, which had been injected with pimozide and LHRHa. Postvitellogenesis persisted for at least four hours after pimozide and LHRHa administration. During this stage a limited rise in the plasma gonadotropin (GTH) level was accompanied by an increase in the testosterone concentration. The estradiol level was high and remained high except for a passing drop during the stage of germinal vesicle migration. At the stage of germinal vesicle migration a strong increase in the plasma GTH level coincided with a maximum in the testosterone concentration and a concomitant increase in the levels of 17alpha,20beta-dihydroxy-4-pregnen-3-one and of five 5beta-reduced pregnanes. During germinal vesicle breakdown the GTH concentration remained high, the plasma level of 17alpha-hydroxyprogesterone tended to increase, and the levels of 5beta-pregnane-3alpha, 17alpha-diol-20-one, 5beta-pregnane 3alpha,17alpha,20beta-triol and 5beta-pregnane-3alpha,17alpha,20alpha-triol reached a maximum. At pre-ovulation the GTH concentration did not change, and peak levels were reached of 17alpha,20beta-dihydroxy-4-pregnen-3-one and 5beta pregnane-3alpha,6alpha,17alpha-triol-20-one. Shortly after ovulation the GTH concentration slightly decreased together with a sharp decline in the concentrations of 17alpha,20beta-dihydroxy-4-pregnen-3-one and the 5beta-reduced steroids, with the exception of 5beta-pregnane-3alpha,17alpha,20alpha-triol, 5beta-pregnane-3alpha,6alpha,17alpha,20beta-tetrol and 5beta-dihydrotestosterone. The plasma concentrations of androstenedione, estrone, etiocholanolone and 5beta androstane-3alpha,17beta-diol showed marginal fluctuations during oocyte maturation and ovulation. Apart from 17alpha,20beta-dihydroxy-4-pregnen-3-one, the 5beta-reduced pregnanes might be candidates for the function of oocyte maturation inducing hormone inC. gariepinus. PMID- 24226975 TI - Steroids and steroid glucuronides in the ovarian fluid of the African catfish,Clarias gariepinus, between ovulation and oviposition. AB - As part of a series of experiments concerning a possible pheromonal function of steroids and steroid glucuronides excreted by the sex organs of the African catfish,Clarias gariepinus, qualitative and quantitative studies, using GCMS, were carried out to examine the presence of the steroids, that can be synthesized by the ovary during oocyte maturation and ovulation, and of the corresponding steroid glucuronides, in the fluid surrounding the eggs in the ovarian cavity shortly after ovulation.Full mass spectra were obtained of 5beta-pregnane 3alpha,17alpha-diol-20-one, 5beta-pregnane-3alpha,17alpha,20alpha-triol, 5beta pregnane-3alpha,6alpha,17alpha-triol-20-one, 5beta-pregnane 3alpha,6alpha,17alpha,20beta-tetrol, 5beta-androstane-3alpha,17beta-diol and 5beta-androstane-3alpha,17beta-diol-11-one. After selected ion monitoring the following steroids could be detected by the presence of at least two characteristic ions at the expected retention time: 5beta-pregnane-3alpha, 17alpha,20beta-triol, etiocholanolone, 5beta-dihydrotestosterone, 5beta androstane-3alpha,11beta-diol-17-one, testosterone and estradiol. After treatment with beta-glucuronidase the following steroids could be determined in a similar way: 5beta-pregnane-3alpha,17alpha-diol-20-one, 5beta-pregnane 3alpha,17alpha,20alpha-triol, 5beta-pregnane-3alpha,17alpha,20beta-triol, 5beta pregnane-3alpha,6alpha,17alpha-triol-20-one, 5beta pregnane,3alpha,6alpha,17alpha,20beta-tetrol, 5beta-androstane-3alpha,17beta diol, etiocholanolone, 5beta-dihydrotestosterone, testosterone and estradiol.The free steroids 5beta-pregnane-3alpha,6alpha,17alpha,20beta-tetrol and 5beta pregnane-3alpha,6alpha,17alpha-triol-20-one and the steroid glucuronides of testosterone, 5beta-dihydrotestosterone and estradiol appeared to be the most abundant of these compounds. The results indicate that very polar steroids and steroid glucuronides, synthesized in the ovary, can be excreted via the ovarian fluid shortly before and during oviposition, and possibly function as sex attractants, inducing reproductive behaviour in male conspecifics. PMID- 24226976 TI - The growth and reproductive endocrinology of adult triploid Pacific salmonids. AB - This paper describes the effect of triploidy on growth and reproductive endocrinology in the months leading up to and including spawning in rainbow trout,Salmo gairdneri, and pink salmon,Oncorhynchus gorbuscha. Growth rates were the same for diploid and triploid rainbow trout, but triploid female pink salmon were smaller than maturing diploid females and diploid and triploid males of the same age. Triploid males of both species developed typical secondary sexual characteristics and had normal endocrine profiles, although their cycle appeared to be delayed by about one month. Triploid females remained silvery in appearance and showed no endocrine signs of maturation, even at the level of the pituitary. Thus, although triploids of both sexes are genetically sterile, only the females do not undergo physiological maturation. PMID- 24226977 TI - Antifreeze proteins in the urine of marine fish. AB - Several species of marine teleosts have evolved blood plasma antifreeze polypeptides which enable them to survive in ice-laden seawater. Four distinct antifreeze protein classes differing in carbohydrate content, amino acid composition, protein sequence and secondary structure are currently known. Although all of these antifreezes are relatively small (2.6-33 kd) it was generally thought that they were excluded from the urine by a variety of glomerular mechanisms. In the present study antifreeze polypeptides were found in the bladder urine of winter flounder (Pseudopleuronectes americanus), sea raven (Hemitripterus americanus), ocean pout (Macrozoarces americanus) and Atlantic cod (Gadus morhua). Since the plasma of each of these fish contains a different antifreeze class it would appear that all four classes of antifreeze can enter the urine. The major antifreeze components in the urine of winter flounder were found to be identical to the major plasma components in terms of high performance liquid chromatography retention times and amino acid composition. It is concluded that plasma antifreeze peptides need not be chemically modified before they can enter the urine. PMID- 24226978 TI - Species-specific composition of free amino acids on the leaf surface of fourSenecio species. AB - The specificity of the chemical composition of the leaf surface of fourSenecio species was studied in order to understand the host selection ofTyria jacobaeae, a monophagous moth that hasSenecio jacobaea as its principal host plant. Pyrrolizidine alkaloids characteristic forSenecio species were not detected in water and sulfuric acid extracts of the leaf surface ofSenecio jacobaea. Water extracts of the leaf surfaces ofS. jacobaea, S. vulgaris, S. viscosus, andS. sylvaticus contained low concentrations of free amino acids. The proportions of these amino acids were very different from those inside the leaf tissues. In a discriminant analysis, the four species could be completely separated on the basis of the relative proportions of amino acids on the leaf surface. PMID- 24226979 TI - Chemosensory predator recognition in the lizardPodarcis hispanica: Effects of predation pressure relaxation. AB - We compared the behavior of two subspecies ofPodarcis hispanica lizards in cages that had been chemically marked by a saurophagous snake, the viperVipera latastei. One of the subspecies (P.h. atrata) has experienced a relaxation from predation pressure by this viper, as snakes were eradicated from the island it inhabits over 100 years ago. Nevertheless, individuals fromP.h. atrata responded to the snake's chemicals similarly to individuals from a population ofP.h. hispanica, currently sympatric withV. latastei. Lizards exhibited more stress indicating behaviors (foot shakes, tail vibrations, sudden starts), became less mobile, and tongue-flicked more while moving in a snake-inhabited terrarium than when in a clean, unfamiliar terrarium. PMID- 24226980 TI - Investigation of the role of diterpenes produced by marine pulmonatesTrimusculus reticulatus andT. conica. AB - The intertidal pulmonate limpetTrimusculus reticulatus, which is found in caves or crevices along the California coast, was previously reported to contain two novel diterpenoids, 6beta-isovaleroxylabda-8,13-dien-7alpha,15-diol (1) and 2alpha,7alpha-diacetoxy-6beta-isovaleroxylabda-8,13-dien-15-ol (2). Dissection of the animals prior to extraction revealed that the diterpenoids were concentrated in the mantle, foot, and mucus, but not in the viscera. The presence ofT. reticulatus or its mucus was toxic to veliger larvae of the sabellariid reef building tube wormPhragmatopoma californica. The major diterpenoid1 was responsible for the observed larvicidal activity. Protection against overgrowth by settling invertebrate larvae is important for the survival of this sessile filter-feeding pulmonate. A related pulmonate,T. conica, which was found in similar intertidal habitats in New Zealand, contained 6beta-acetoxy-7alpha isovaleroxylabda-8,13-dien-15-oic acid (3) and 1beta,7beta,12beta,18-tetraacetoxy cholest-5-en-3beta-ol (4). The diterpene3 was also localized in the foot, mantle, and mucus ofT. conica but was not larvicidal toP. californica. PMID- 24226981 TI - Ant repellent effect of the sternal gland secretion ofPolistes dominulus (Christ) andP. sulcifer (Zimmermann). (Hymenoptera: Vespidae). AB - The long-chain carboxylic acids identified in the sternal gland secretion ofPolistes dominulus andP. sulcifer females were tested individually on three species of ants,Crematogaster scutellaris, Formica cunicularia, andLasius sp., in order to verify if they have a repellent effect. The unsaturated acids (palmitoleic, linoleic, and oleic) act as repellents of all three ant species, while the saturated acids (lauric, myristic, palmitic, and stearic) have no effect. The mixture reproducing the secretion of the sternal glands ofP. dominulus maintained its repellency for at least four days. PMID- 24226982 TI - Isolation and identification of house fly,Musca domestica L., repellents from pepper tree,Schinus molle L. AB - Foliage from the pepper tree,Schinus molle L., is traditionally used in Ethiopia to "repel" house flies,Musca domestica L. The volatile extracts of pepper tree leaves were shown to have repellent and feeding-deterrent activity against house flies in a two-choice laboratory bioassay. High-performance liquid chromatographic fractionation of steam-distilled volatiles from leaves, monitored by laboratory bioassays, demonstrated that bioactivity is associated with two compounds,cis-menth-2-en-1-ol andtrans-piperitol. The absolute configuration of the latter was established as (1S,6S)-piperitol by comparison of acetyl lactate derivatives. Racemic compounds were synthesized from piperitone, and bioassays with house flies indicatedtrans-piperitol to be the most active house fly repellent. PMID- 24226983 TI - Effects of octadecanoid metabolites and inhibitors on induced nicotine accumulation inNicotiana sylvestris. AB - We examined the effects of inhibitors of the octadecanoid pathway (n-propyl gallate, acetosalicylic acid, salicylhydroxamic acid, methyl salicylate, and antipyrine) on wound- and jasmonate-induced nicotine accumulation and compared the nicotine-inducing ability of exogeneous additions of linolenic acid (18:3) and its methyl ester, linoleic acid (18:2), abscisic acid, traumatic acid, and methyl dihydrojasmonate to the nicotine-inducing ability of exogenous additions of methyl jasmonate (MJ). The first four of these inhibitors significantly reduced wound-induced nicotine accumulation when applied in a lanolin paste to wounded tissues immediately after wounding at concentrations of 89-90ug/plant. When methyl salicylate and propyl gallate were mixed individually with MJ, neither inhibited MJ-induced nicotine synthesis, which suggests that the inhibitors block jasmonate synthesis or release from stored pools and not its effects. Linolenic acid or its methyl ester applied to undamaged plants or damaged plants (to either damaged or undamaged leaves) or to the roots of hydroponically growing plants did not induce nicotine accumulation or increase nicotine accumulation above levels found in damaged plants. Similarly, traumatic acid, linoleic acid, and abscisic acid did not induce nicotine accumulations. Methyl dihydrojasmonate, which is biosynthetically derived from linoleic acid, had 12-56% of the nicotine-inducing acitivity of MJ when added to the roots of hydroponically grown plants. The signal transduction pathway mediating wound induced nicotine production therefore shares many features of the pathway eliciting wound-induced proteinase inhibitor production but differs in not being regulated at the lipase step in jasmonic acid production and not being responsive to abscisic acid. PMID- 24226984 TI - Identification of sex pheromone ofTetanolita mynesalis (Lepidoptera: Noctuidae), a prey species of bolas spider,Mastophora hutchinsoni. AB - The bolas spider,Mastophora hutchinsoni, attracts adult males of four species of nocturnally active Lepidoptera through aggressive chemical mimicry of those species' sex pheromones. Here we report the identification of the sex pheromone of one prey species, the smoky tetanolita (Tetanolita mynesalis). In sex pheromone gland extracts, only two peaks stimulated an electrophysiological response as measured by a coupled gas chromatography-electroantennographic detection analysis. These two peaks had retention times identical to (3Z,6Z,9Z) heneicosatriene (3Z,6Z,9Z-21:H) and (3Z,9Z)-cis-6,7-epoxy-heneicosadiene (3Z,9Z cis-6,7-epoxy-21:H), respectively, and mass spectra identical to these two compounds. It was determined that 0.23+/-0.16 and 0.56+/-0.26 ng of 3Z,6Z,9Z-21:H and 3Z,9Z-cis-6,7-epoxy-21:H, respectively, were present in pheromone gland extracts from individual females. A 1:1 blend of 3Z,6Z,9Z-21:H and 3Z,9Z-6S,7R epoxy-21:H was an effective attractant for adult males from feral populations. Blend ratios of these two components from 2:1 to 1:2 were equally effective as attractants. Greater deviation from the optimal blends resulted in diminished trap catches. The enantiomer 3Z,9Z-6R,7S-epoxy-21:H not only was not effective in attracting males, its presence in the effective blend shut down trap catches. These results indicate that the pheromone blend consists of 3Z,6Z,9Z-21:H and 3Z,9Z-6S,7R-epoxy-21:H. This is the first report of a hydrocarbon/epoxide pheromone for a prey species of this bolas spider. Sex attractants or pheromones for the other three prey species are composed of aldehydes or acetates. PMID- 24226985 TI - Biological performance of Colorado potato beetle larvae on potato genotypes with differing levels of polyphenol oxidase. AB - Two potato genotypes resistant to the Colorado potato beetle (CPB) and three susceptible genotypes were used to investigate the role of total foliar polyphenol oxidase (PPO) on the performance of CPB larvae in long-term feeding assays. A significant positive correlation was found between larval mortality and PPO content in potato foliage. Moreover, a significant negative correlation was also observed between PPO content and larval weight, fecundity, and relative larval growth rate. These results suggest a significant role of PPO in conferring potato resistance to the Colorado potato beetle at least in those clones where the PPO levels were above a certain threshold. PMID- 24226986 TI - Sex pheromone of caddisflyHesperophylax occidentalis (Banks) (Trichoptera: Limnephilidae). AB - The main component of the sex pheromone of the caddisflyHesperophylax occidentalis (Banks) (Trichoptera: Limnephilidae) was identified as 6-methylnonan 3-one (enantiomeric composition has not yet been determined). Extracts of adult females elicited strong electroantennogram (EAG) responses from adult male antennae, but elicited significantly smaller EAG responses from adult female antennae. Extracts of adult males did not elicit appreciable EAG responses from antennae of either sex. Racemic 6-methylnonan-3-one was synthesized and elicited EAG responses from male antennae as strong as those obtained with female extracts. In field tests with baited sticky traps near lakes and streams, traps baited with synthetic racemic 6-methylnonan-3-one caught significantly more males than control traps. Female adults contained approximately 1 ug of 6-methylnonan-3 one per individual. Related ketones and alcohols of other chain lengths were also tentatively identified, being present in tiny amounts in female extracts. Extraction of different body parts showed that 6-methylnonan-3-one occurs only in a region near the intersegmental membrane between the fourth and fifth abdominal sternites of the female (no discrete glands were observed). Extracts of males did not contain 6-methylnonan-3-one, nor did pupae of either sex. PMID- 24226987 TI - Hesperophylax occidentalis (Trichoptera: Limnephilidae): Electroantennogram structure-activity study of sex pheromone component 6-methylnonan-3-one. AB - Electroantennogram (EAG) analyses ofHesperophylax occidentalis male and female antennae were used to generate dose-response curves for synthetic, racemic 6 methylnonan-3-one and to demonstrate the chemical specificity of male antennal olfactory cells. Male antennae responded to 6-methylnonan-3-one, the main female pheromone component. Females also demonstrated a response to 6-methylnonan-3-one, but a smaller one than males. The chemical specificity of male antennal receptors was determined by comparing EAG activity of synthetic, racemic 6-methylnonan-3 one and a series of structural analogs. The three structural parameters considered, including keto position, chain length, and methyl-group position, were demonstrated to contribute significantly to the reception of synthetic, racemic 6-methylnonan-3-one by male antennae. For straight-chain nonanones with keto groups at different positions, nonan-3-one elicited the greatest EAG responses from male antennae. For straight-chain alkan-3-ones with different chain lengths, the EAG responses of male antennae to nonan-3-one and decan-3-one were the same, but greater than those to other chain lengths. For methyl-branched nonan-3-ones, 6-methylnonan-3-one elicited greater EAG responses from antennae than analogs with the methyl group at another position. PMID- 24226988 TI - Feeding and oviposition deterrent activities of flower buds of globemallow,Sphaeralcea emoryi torrey, against boll weevil,Anthonomus grandis Boheman (Coleoptera: Curculionidae). AB - The globemallow,Sphaeralcea emoryi Torrey, a plant native to Arizona was evaluated as a source of feeding or oviposition deterrents to the boll weevil,Anthonomus grandis Boheman. Feeding and oviposition responses of reproductive weevils to the flower buds and artificial diets spiked with dry powder or extracts of the globemallow buds were determined. Boll weevils were deterred from feeding and ovipositing in the flower buds unless the calyxes were removed. Male and virgin female weevils were discouraged from feeding as much as gravid weevils. Secondary chemicals in the flower buds served primarily as feeding deterrents but also prevented oviposition. The concentration of these chemicals was highest in the calyxes of the buds, and potent deterrent activity could be extracted from the calyxes with methanol. Boll weevils were able to perceive the deterrents by contact chemosensory organs on the antennae, maxillary palps and labial palps. PMID- 24226989 TI - Phytotoxicity of sesquiterpene lactone parthenin on aquatic weeds. AB - The sesquiterpene lactone parthenin, one of the major toxins in an obnoxious weed, parthenium (Parthenium hysterophorus L.), was toxic at 50 ppm to the floating aquatic weeds pistia (Pistia stratiotes L.) and lemna (Lemna pausicostata Hegelm.) and at 100 ppm to water hyacinth (Eichhornia crassipes Mart Solmns.), salvinia (Salvinia molesta Mitchell), azolla (Azolla nilotica Decne.), and spirodella (Spirodella polyrhiza L. Schleid). The lethal dose for the submerged weeds najas (Najas graminea Del.), ceratophyllun (Ceratophyllum demersun L.), and hydrilla (Hydrilla verticillata L. f. Royle) was 25 ppm. The submerged aquatic weeds were more sensitive to parthenin. Water hyacinth was used as a representative for studying the phytotoxicity of parthenin on aquatic weeds. Inhibition of water hyacinth by parthenin was associated with decline in water use, root dysfunction, excessive leakage of solutes from roots indicative of massive damage to cellular membranes, loss of dehydrogenase activity in the roots, and loss of chlorophyll in the leaves. Plant death occurred in a period of one to two weeks. Parthenin phytotoxicity is gradually lost in an aquatic environment as a lethal dose became nonlethal in about 30 days under outdoor conditions. Possible buildup of a toxin concentration may affect population dynamics and a shift in the aquatic weed flora in the immediate area of parthenium stands. Accumulation of the toxin in an aquatic environment, however, at a level sufficient to produce such changes in a natural ecosystem as a consequence of rain washing parthenium plants and leaching of toxin from their residue appears to be unlikely. PMID- 24226990 TI - Oviposition response ofLobesia botrana females to long-chain free fatty acids and esters from its eggs. AB - Avoidance of occupied ovisposition sites supposes that females perceive information related to their own progency. Fatty acids identified from egg extracts have been reevaluated using a different extraction method, and we have investigated the dose-dependent oviposition response of European grape vine moths (Lobesia botrana) to myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, methyl palmitate, methyl oleate, and ethyl palmitate; all except ethyl palmitate have been identified from eggs ofL. botrana. A methylene dichloride extract of eggs fromL. botrana revealed the presence of saturated free fatty acids (myristic, palmitic, and stearic) and unsaturated acids (palmitoleic, oleic, linoleic, and linolenic) in amounts ranging from 3.9 ng/egg equivalent for myristic acid to 30 ng/egg equivalent for palmitic and oleic acids. The extract also contained traces of methyl palmitate and methyl stearate. The greatest avoidance indexes were observed in response to palmitic, palmitoleic, and oleic acids. All the other compounds tested caused weaker responses. A reduction in the number of eggs laid was observed when moths were exposed to each of the esters applied at 0.3 ug per application spot. Reduction in eggs laid was also observed at a 10-fold higher dose of oleic acid. The present results confirm that general and simple molecules can be involved in the regulation of oviposition site selection and that they may participate in chemical marking of the eggs. PMID- 24226991 TI - Fluorescence of the Schiff bases of pyridoxal and pyridoxal 5'-phosphate withL isoleucine in aqueous solutions. AB - The present study reports on the absorption and emission properties of the Schiff bases formed by pyridoxal and pyridoxal 5'-phosphate withL-isoleucine in aqueous solutions. Species protonated at the imine and ring nitrogen are the most fluorescent in both Schiff bases with a quantum yield of 0.02, i.e., 20-fold the value found for species in alkaline solutions. In agreement with other studies, species protonated at the imine nitrogen shows an emission around 500 nm upon excitation at 415 nm. In contrast to previous observations on other PLP Schiff bases, emissions at 560 nm (PL-Ile) and 540 nm (PLP-Ile) are observed upon excitation at 365 and 415 nm, respectively. The emission at 470 nm found in PLP Ile Schiff base upon excitation at 355 nm is ascribed to a multipolar monoprotonated species. An estimation for the pK a of the imine in the excited state ( ~ 8.5) for both Schiff bases is also reached. Our results suggest that fast protonation reactions on the excited state are responsible for the observed fluorescence. These effects, in which the hydrogen bond and the phosphate group seem to play a role, could be extended to understanding coenzyme environments in proteins. PMID- 24226992 TI - Ground- and excited-state spectroscopic studies on [1-(4-methoxyphenyl)-3-(amino) 2,4-(dicyano)-9,10-tetrahydrophenanthrene]. AB - The effects of polar and nonpolar solvents on both the ground and the excited state properties of [1-(4-methoxyphenyl)-3-(amino)-2,4-(dicyano)-9,10 tetrahydrophenanthrene] is examined. Light absorption results in a population of a locally excited (LE) first singlet state (S1,npi(*)) which shows sensitivity to the polarity of the surrounding solvent and hydrogen-bonding ability to the quencher 4-methylpyridine. Relaxation of this state leads to an intramolecular charge-transfer state (ICT) which leads to a large Stokes shift in polar solvents and an excited-state dipole moment of MUe= 10D. The quenching of the fluorescence state by 4-methylpyridine studied inn-hexane and acetonitrile at room temperature is found to be efficient and a positive deviation from linearity was observed in the Stern-Volmer plots even at concentrations of 4-methylpyridine below 0.4M. This is explained as a result of the occurrence of both a dynamic and a static quenching mechanism. The static quenching constants (K sv) along with those obtained by visible spectroscopy (K GS) indicate that the ground-state complex is weak and relatively solvent dependent. PMID- 24226993 TI - Use of the SPP scale for the analysis of molecular systems with dual emissions resulting from the solvent polarity. AB - The solvent polarity/polarizability (SPP) scale is shown to be highly useful for analyzing the solvatochromic behavior of molecular systems emitting dual fluorescence by virtue of the solvent polarity. Stokes' shift data are presented on a test set of seven solutes in 58 solvents correlating with the SPP (single parameter polarity/polarizability index). SPP values for seven further solvents are given, extending the previously available list. PMID- 24226994 TI - Extrinsic fluorescence probe study of human serum albumin using Nile red. AB - Nile red bound to human serum albumin (HSA) shows an order of magnitude increase in the probe's fluorescence intensity. Here, we report on the fluorescence characteristics of the probe-protein complex in Trizma buffer (pH 7.1), urea, guanidine hydrochloride, and AOT/isooctane/buffer reverse micelles using both steady-state and time-resolved fluorescence techniques. With a view to illustrating the use of extrinsic probe fluorescence spectroscopy in protein research, we demonstrate that protein unfolding can be observed through measurements of the probe's time-resolved anisotropy and steady-state fluorescence spectrum. Moreover, this shows that thermal unfolding is fundamentally different from using denaturant, with respect to changes in both the nanosecond diffusional rotation of the probe at intermediate stages and in the denatured protein's structure. Also, the large Stokes shift of Nile red allows the changes in the environment of the probe-protein complex in reverse micelles of varying waterpool size to be easily identified in the steady-state fluorescence. This was not seen in earlier work exploiting the intrinsic tryptophan fluorescence of HSA and further demonstrates the complementary information that extrinsic fluorescence probe studies can offer protein science. We discuss the complex acrylamide quenching characteristics of Nile red bound to HSA in terms of the possibility of at least two binding sites for the probe and the effect of acrylamide on the probe-protein structure at very high quencher concentrations. PMID- 24226995 TI - Two distinguishable fluorescent modes of 1-anilino-8-naphthalenesulfonate bound to human albumin. AB - We study the interaction of 1-anilino-8-naphthalenesulfonate (ANS) with human (HSA) and bovine serum albumin (BSA) by phase and modulation fluorescence spectroscopy. We determined that both HSA and BSA show one or two distinguishable fluorescent sites, depending of the ANS/serum albumin ratio. At above a 1?1 ANS/HSA molar ratio, the steady-state emission spectra for ANS can be resolved in two components: component 1, emitting with a lifetime (tau1) of 16 ns and a lambda1max of 478 nm, with a quantum yield (ff1) of 0.67, and component 2, with a lifetime (tau2) of 2-4 ns and a lambda2max of 483 nm, with an average quantum yield (ff2) of about 0.11. Considering these findings, the binding analysis is fitted with a model of two independent sites. Site 1 has an association constantK as1=0.87*10(6)M(-1) and a capacity of 1.04 mol of ANS/mol of HSA, and site 2 aK as2=0.079*10(6)M(-1) and a capacity of 2.34 mol of ANS/mol of HSA. Analysis of fluorescence lifetime distributions shows that the rigidity of the fluorophore environment at site 1 changes when site 2 is occupied. These findings suggest an interconnection between the two sites and that ligands can stabilize the protein's globular structure. To assess the identity of the ANS binding sites we used diazepam as a marker of the site located at the IIIA HSA subdomain and aspirin as a marker of sites located at the IIIA and IIA HSA subdomains. Both ligands displace ANS only from site 1, suggesting that it corresponds to the binding site located at the IIIA sub-domain of the protein. We determined that theK as values for diazepam and aspirin are 0.113* 10(6) and 0.021*10(6) M (-1) respectively. PMID- 24226996 TI - Intramolecular energy transfer in compounds with two 1-pyrenoate groups separated by methylene spacers. AB - Steady-state fluorescence anisotropy (r) and fluorescence lifetime (tau) measurements have been used to study the efficiency of nonradiative singlet energy transfer as a function of alkane size in 1-pyrenecarboxylic acid alkanediyl esters (as a function ofm in Py-COO-(CH2) m -OOC-Py, where Py denotes pyrene substituted in the 1-position, andm=2-6). Experiments were performed in media of different viscosity, eta, obtained by changing the temperature (from -20 to 40 degrees C) of dilute solutions in ethylene glycol and by examination of the compounds in a solid matrix of poly(methyl methacrylate) (PMMA) at ambient temperature. The Py-COO-(CH2)m-OOC-Py exhibit intramolecular excimer emission in ethylene glycol at these temperatures, but the intensity of this emission is much lower than when these compounds are placed in common solvents of lower eta. The values of tau indicate that excitation hopping or intramolecular energy transfer takes place between the chromophores attached to the ends of the alkane bridges. Values ofr obtained by the extrapolationsT/eta->0 ortauT/eta->0 in ethylene glycol, as well as the values obtained in the rigid matrix of PMMA, show very little dependence onm. A theoretical conformational analysis, using the rotational isomeric state (RIS) model, was also performed. The combination of the experimental results forr in the media of high eta with the theoretical (RIS) analysis produces an estimated value of 21 +/-2 A for the Forster radius in Py COO-(CH2)m-OOC-Py. PMID- 24226997 TI - Fluorescence of horse liver alcohol dehydrogenase using one- and two-photon excitation. AB - We examined the steady-state and time-resolved emission of liver alcohol dehydrogenase resulting from one-photon and two-photon excitation. Previous studies with one-photon excitation revealed that the two nonidentical tryptophan residues display different emission spectra and decay times. The use of two photon excitation resulted in similar emission spectra, multiexponential intensity decays, time-resolved emission spectra, and anisotropy decays as was observed for one-photon excitation. These results suggest that both nonidentical tryptophan residues are excited to a similar extent for one- and two-photon excitation. However, the limiting anisotropy (r 0) with two-photon excitation from 585 to 610 nm is below 0.1 and appears distinct from that observed previously forN-acetyl-L-tryptophanamide. PMID- 24226998 TI - The spine. PMID- 24226999 TI - Drug development: Chemical brace. PMID- 24227000 TI - Perspective: Protecting the neck. PMID- 24227001 TI - Emergency medicine: The need for speed. PMID- 24227002 TI - Technology: Mobility machines. PMID- 24227003 TI - Perspective: Avoiding injury. PMID- 24227004 TI - Sensation and loss. PMID- 24227005 TI - Stem cells: A time to heal. PMID- 24227006 TI - Regenerative medicine: Rebuilding the backbone. PMID- 24227007 TI - Canine mammary tumors: a review and consensus of standard guidelines on epithelial and myoepithelial phenotype markers, HER2, and hormone receptor assessment using immunohistochemistry. AB - Although there have been several studies on the use of immunohistochemical biomarkers of canine mammary tumors (CMTs), the results are difficult to compare. This article provides guidelines on the most useful immunohistochemical markers to standardize their use and understand how outcomes are measured, thus ensuring reproducibility of results. We have reviewed the biomarkers of canine mammary epithelial and myoepithelial cells and identified those biomarkers that are most useful and those biomarkers for invasion and lymph node micrometastatic disease. A 10% threshold for positive reaction for most of these markers is recommended. Guidelines on immunolabeling for HER2, estrogen receptors (ERs), and progesterone receptors (PRs) are provided along with the specific recommendations for interpretation of the results for each of these biomarkers in CMTs. Only 3+ HER2 positive tumors should be considered positive, as found in human breast cancer. The lack of any known response to adjuvant endocrine therapy of ER- and PR positive CMTs prevents the use of the biological positive/negative threshold used in human breast cancer. Immunohistochemistry results of ER and PR in CMTs should be reported as the sum of the percentage of positive cells and the intensity of immunolabeling (Allred score). Incorporation of these recommendations in future studies, either prospective or retrospective, will provide a mechanism for the direct comparison of studies and will help to determine whether these biomarkers have prognostic significance. Finally, these biomarkers may ascertain the most appropriate treatment(s) for canine malignant mammary neoplasms. PMID- 24227008 TI - Laser capture microdissection for the investigative pathologist. AB - An important step in translational research is the validation of molecular findings from in vitro experiments using tissue specimens. However, tissue specimens are complex and contain a multitude of diverse cell populations that interfere with the molecular profiling data of a specific cell type. Laser capture microdissection (LCM) alleviates this issue by providing a valuable tool for the enrichment of a specific cell type within complex tissue samples. However, LCM and molecular analysis from tissue specimens can be complex and challenging due to numerous issues related with the tissue processing and its impact on the integrity of biomolecules in the specimen. The intricate nature of this application highlights the essential role a pathologist plays in translational research by contributing an expertise in histopathology, tissue handling, tissue analysis techniques, and clinical correlation of biological findings. The present review examines key practical aspects in tissue handling, specimen selection, quality control, and sample preparation for LCM and downstream molecular analyses that are a primary objective of the investigative pathologist. PMID- 24227009 TI - Veterinary and human biobanking practices: enhancing molecular sample integrity. AB - Animal models have historically informed veterinary and human pathophysiology. Next-generation genomic sequencing and molecular analyses using analytes derived from tissue require integrative approaches to determine macroanalyte integrity as well as morphology for imaging algorithms that can extend translational applications. The field of biospecimen science and biobanking will play critical roles in tissue sample collection and processing to ensure the integrity of macromolecules, aid experimental design, and provide more accurate and reproducible downstream genomic data. Herein, we employ animal experiments to combine protein expression analysis by microscopy with RNA integrity number and quantitative measures of morphologic changes of autolysis. These analyses can be used to predict the effect of preanalytic variables and provide the basis for standardized methods in tissue sample collection and processing. We also discuss the application of digital imaging with quantitative RNA and tissue-based protein measurements to show that genomic methods augment traditional in vivo imaging to support biospecimen science. To make these observations, we have established a time course experiment of murine kidney tissues that predicts conventional measures of RNA integrity by RIN analysis and provides reliable and accurate measures of biospecimen integrity and fitness, in particular for time points less than 3 hours post-tissue resection. PMID- 24227010 TI - Megaesophagus in Friesian horses associated with muscular hypertrophy of the caudal esophagus. AB - Friesian horses have a perceived high rate of congenital or hereditary diseases, including megaesophagus, that may lead to choke and death. A retrospective study was performed to determine the prevalence and pathologic characteristics of esophageal disease in 852 horses, including 17 Friesians, that had been necropsied over a 6-year period at the Diagnostic Center for Population and Animal Health. Forty-two horses had grossly described esophageal lesions (25 muscular hypertrophy, 7 hemorrhage, 6 megaesophagus, 4 erosion/ulceration, 3 obstruction, 2 tears, 2 secondary neoplasms, 2 lymphoid patches, 1 thin wall, 1 esophagitis). Some of these lesions occurred concurrently in the same horse. Ten of these horses died or were euthanatized because of severe esophageal disease (6 megaesophagus causing tears in 2 horses, 3 esophageal obstruction with food bolus, and 1 esophagitis). All 6 horses with megaesophagus were Friesians. No cause for megaesophagus was noted in the necropsy reports; however, 5 of these 6 Friesians had marked caudal esophageal muscular hypertrophy (wall thickness: 1.9 +/- 0.3 cm). Microscopic review of the esophagus of these Friesians confirmed smooth muscle hypertrophy, with no obvious fibrosis, degeneration, or loss of myenteric plexi. Unlike the Friesians, the 4 non-Friesian horses with severe esophageal disease had esophageal obstruction with an intraluminal food bolus or severe esophagitis. None had caudal esophageal muscular hypertrophy. It is concluded that in comparison to other horse breeds, Friesians have a higher prevalence of severe esophageal disease, specifically megaesophagus, that is commonly associated with marked caudal muscular hypertrophy. PMID- 24227011 TI - Switching light with light--advanced functional colloidal monolayers. AB - Colloidal monolayers comprising of highly ordered two dimensional crystals are of high interest to generate surface patterns for a variety of different applications. Mostly, unfunctionalized polymer or silica colloids are assembled into monolayers. However, the incorporation of functional molecules into such colloids offers a convenient possibility of implementing additional properties to the two-dimensional crystal. Here, we present the formation of novel functional colloidal monolayers with photoswitchable fluorescence. The miniemulsion polymerization technique was used to incorporate an appropriate dye system of a perylene-based fluorophore and a bis-arylethene as a photochrome in polymeric colloids in defined ratios. Upon irradiation with UV or visible light the photochrome reversibly isomerizes from the ring-closed form, which is able to absorb light of the emission wavelength of the fluorescent dye and the ring-open form, which is not. The fluorescence emission of the dye can thus be reversibly switched on and off with light even when embedded in colloids. The colloids were self-assembled at the air-water interface to produce hexagonally ordered functional monolayers and more complex binary crystals. We investigate in detail the influence of the polymeric matrix on the switching properties of the fluorophore/photochrome system and find that the rate constants for the photoswitching, which all lie in the same range, are less influenced by the polymeric environment than expected. We demonstrate the reversible switching of the fluorescence emission in self-assembled colloidal monolayers. The arrangement of broadly distributed functional colloids into ordered monolayers with high addressability was obtained by the formation of binary colloidal monolayers. PMID- 24227012 TI - Analysis of Sartans: a review. AB - The risk of cardiovascular diseases is closely related to hypertension, high cholesterol levels, and diabetes. When these risk factors appear together they are referred to as a metabolic syndrome. In the treatment of cardiovascular diseases, a combination of antihypertensive, hypolipemiant, and antidiabetic drugs is often applied. Diuretics (chlortalidone, hydrochlorothiazide, etc.) and angiotensin II receptors antagonist (sartans) are used to control hypertension, whereas statins (fluvastatin, simvastatin, etc.) are used to reduce cholesterol levels. This review is concerned with methods for the analysis of sartans in various matrices, such as pharmaceutical formulations, environmental and biological samples, and discusses the current status of stability studies of sartans . It also presents analytical methods for the simultaneous determination of sartans, diuretics, and statins. PMID- 24227013 TI - Quinoline-attached triazacyclononane (TACN) derivatives as fluorescent zinc sensors. AB - TACN (1,4,7-triazacyclononane) derivatives with three 6-methoxy-2-quinolylmethyl or 1-isoquinolylmethyl moieties were examined as fluorescent zinc sensors. Upon the addition of zinc, 6-MeOTQTACN (5) exhibited a 9-fold fluorescence increase at 420 nm (lambdaex = 341 nm, phiZn = 0.070). Fluorescence enhancement is specific for zinc and cadmium, although cadmium induces smaller increases (ICd/I0 = 3.6 and ICd/IZn = 40%). The isoquinoline analog 1-isoTQTACN (6) exhibits minimal fluorescence enhancement upon zinc binding. TPEN (N,N,N',N'-tetrakis(2 pyridylmethyl)ethylene-diamine) does not extract zinc from the 6-MeOTQTACN-Zn complex (5-Zn). The quantum yield, metal ion selectivity and metal binding affinity differences between TACN and ethylenediamine (EN) skeletons in quinoline based ligands are discussed based on the X-ray crystallographic analysis of zinc and cadmium complexes, demonstrating the superiority of quinoline-TACN conjugates. PMID- 24227014 TI - Family nursing is more than family centered care. PMID- 24227016 TI - Longitudinal associations between neighborhood recreational facilities and change in recreational physical activity in the multi-ethnic study of atherosclerosis, 2000-2007. AB - Many cross-sectional studies have investigated the relationship between neighborhood physical environment and physical activity. However, few studies have examined this relationship longitudinally, and no study has examined the association between change in objective measurements of physical activity resources and change in physical activity in adults. We used longitudinal data from the Multi-Ethnic Study of Atherosclerosis (2000-2007) of 6,814 adults who were aged 45-84 years at baseline. Physical activity was assessed via a semiquantitative questionnaire at baseline and at 2 follow-up visits (approximately 1.6 and 3.2 years later). We measured the density of recreational facilities within 1 mile of each participant's home address and used linear mixed effects models to estimate the association between change in recreational facility density and change in physical activity. After adjusting for potential confounders, we found that a greater increase in recreational density was associated with a less pronounced decline in physical activity (mean difference in annual change in physical activity for each 1-unit increase in recreational density over time = 10.3 (95% confidence interval: 0.7, 19.9)). This association was stronger in older adults. Better access to recreational facilities may benefit middle-aged and older adults by enabling them to maintain activity levels as they age. PMID- 24227017 TI - Associations between short-term changes in air pollution and correlates of arterial stiffness: The Veterans Affairs Normative Aging Study, 2007-2011. AB - We investigated associations between short-term exposure to air pollution and central augmentation index and augmentation pressure, correlates of arterial stiffness, in a cohort of elderly men in the Boston, Massachusetts, metropolitan area. This longitudinal analysis included 370 participants from the Veterans Affairs Normative Aging Study with up to 2 visits between 2007 and 2011 (n = 445). Augmentation index (as %) and augmentation pressure (in mmHg) were measured at each visit by using radial artery applanation tonometry for pulse wave analysis and modeled in a mixed effects regression model as continuous functions of moving averages of air pollution exposures (over 4 hours and 1, 3, 7, and 14 days). The results suggest that short-term changes in air pollution were associated with augmentation index and augmentation pressure at several moving averages. Interquartile range (IQR) increases in 3-day average exposure to particles with aerodynamic diameter less than 2.5 MUm (3.6-MUg/m(3) IQR increase) and sulfate (1.4-MUg/m(3) IQR increase) and 1-day average exposure to particle number counts (8,741-counts/cm(3) IQR increase) were associated with augmentation index values that were 0.8% (95% confidence interval (CI): 0.2, 1.4), 0.6% (95% CI: 0.1, 1.2), and 1.7% (95% CI: 0.4, 2.9) higher, respectively. Overall, the findings were similar for augmentation pressure. The findings support the hypothesis that exposure to air pollution may affect vascular function. PMID- 24227018 TI - 'Consumed by breathing' - a critical interpretive meta-synthesis of the qualitative literature. AB - OBJECTIVE: To derive an improved understanding of how patients respond to, appraise, and understand the experience of an acute exacerbation of chronic obstructive pulmonary disease via a critical interpretive meta-synthesis. METHODS: Search terms - Exacerbate* OR hospital* AND 'Chronic obstructive' OR emphysema OR bronchitis AND interview* OR qualitative. Inclusion criteria - Primary research published in English of patients' experiences of an acute exacerbation of chronic obstructive pulmonary disease. Data extraction and synthesis - eight papers were identified. Data were extracted by three researchers and constructs elicited via reciprocal translational analysis. FINDINGS: Themes reflected two domains of understanding an acute exacerbation: (1) Acute effect - encompassing intense emotions, somatic awareness and patients need for rescue. (2) Sustained regulation - reflecting life as interrupted, ongoing beliefs and behaviour and help-seeking. DISCUSSION: Acute exacerbations of chronic obstructive pulmonary disease result in heightened patient arousal, vigilance and powerlessness in response to symptoms. Ongoing, psychological interventions which promote partnership working by both acknowledging patients fear and shaping their appraisals may mitigate distress, enhancing the impact of health messages and engagement in pulmonary rehabilitation. PMID- 24227019 TI - Reproducibility of the quantification of arterial and tissue contributions in multiple postlabeling delay arterial spin labeling. AB - PURPOSE: To evaluate the reproducibility of estimation of cerebral blood flow (CBF), bolus arrival time (BAT), and arterial blood volume (aBV) from arterial spin labeling (ASL) data acquired at multiple postlabeling delays (PLDs). MATERIALS AND METHODS: CBF, BAT, and aBV parameters were estimated from flow suppressed and nonflow-suppressed multiple-PDL PICORE-Q2TIPS ASL using model based Bayesian and least-squares fitting frameworks, and aBV was also obtained from a model-free approach. Reproducibility of these parameters was assessed by computing the within- and between-subject coefficients of variability (CVw and CVb). RESULTS: CVw and CVb were comparable across model-based approaches, but were greater for the aBV from the model-free approach. Overall, the Bayesian model estimation procedure was found to provide the best compromise between reliability and reproducibility, yielding CVw/CVb values of 21/21, 3/4, and 24/26% for CBF, BAT, and aBV, respectively. Although a CBF range of 45 mL/100g/min to 59 mL/100g/min was found on average and a BAT of 0.7-1.0 seconds across methods, the corresponding maps were comparable in terms of the parameters' spatial distributions, and in particular in the identification of macrovascular locations, as assessed through comparison with time-of-flight images. CONCLUSION: Reproducible estimates of CBF, BAT, and aBV values can be obtained from non-macroflow-suppressed ASL using both least-squares and Bayesian model-based methods. PMID- 24227020 TI - One-pot synthesis of 3-alkylidenephthalides from benzoic acids by a rhodium catalyzed ortho-C-H acylation process. PMID- 24227021 TI - Persistent polyclonal B lymphocytosis. PMID- 24227022 TI - Physical map of chloroplast DNA of aerial yam, Dioscorea bulbifera L. AB - A physical map of chloroplast DNA (ctDNA) of aerial yam, Dioscorea bulbifera L. was constructed using three restriction endonucleases, PstI, SalI, and SmaI. In addition, a clone bank of the BamHI-digested fragments were generated, and the locations of most BamHI fragments on the map were also determined. The ctDNA of D. bulbifera was found to be a circular molecule with a total size of ca. 152 kb involving two inverted repeats of ca. 25.5 kb, and small and large single copy regions of ca. 18.5 and 83.4 kb, respectively. The genes for the large subunit of the ribulose 1,5-bisphosphate carboxylase (rbcL) and the ATP-synthase subunits beta and E (atpB/atpE) were mapped. PMID- 24227023 TI - Developmental mutants showing abnormal organ differentiation in rice embryos. AB - Zygotes of rice (Oryza sativa L. cv Taichung 65) were treated with 1.0 mM solution of the chemical mutagen N-methyl-N-nitrosourea. Out of 1420 M2 lines, 28 single-locus recessive mutants on embryogenesis were identified. Among them, we analyzed 11 mutants in the present study, which differentiated the shoot (plumule) and/or root (radicle) with abnormality. Of the 11 mutants, two showed no shoot differentiation with normal root. On the other hand, we could not detect any mutant which exhibited a normal shoot without a root. This suggests that shoot and root are genetically controlled by different loci and that the alleles associated with shoot formation mutate more frequently than do those of the root. Five mutants showed aberrant morphology of shoot when both the shoot and root developed. One of them, odm 5 (organ differententiation mutant 5) was germinable, but produced many fine and twisted leaves. This mutant was, however, lethal at the early post-germination stage under the usual cultural conditions. In another mutant (odm 4), shoot differentiation seemed to be initiated at an arbitrary position, resulting in a very abnormal morphology of the shoot when the position fronted the endosperm. The other two mutants showed abnormal morphology of both the shoot and root. One (odm 11) of the remaining two mutants showed a wide variation of abnormalities including no organ differentiation, either shoot or root differentiation and the development of both shoot and root with abnormalities. The last one (odm 16) was unique. It had an embryo with normal shoot and root but the embryo size was only one-third to one-half of normal embryos in length. Of course, the shoot and root are also small but viable. Therefore, odm 16 is considered to be a mutant in the size regulation of the embryo. Although an allelism test has not yet been done, most of these mutants are probably non-allelic, as the phenotypic abnormality differs largely with each one. In rice, the shoot and root highly differentiate in contrast to dicotyledonous embryo. Accordingly, these developmental mutants are very useful materials for investigating the regulatory mechanism of gene expression in organ differentiation. PMID- 24227024 TI - Identification of 2n breeding lines and 4n varieties of potato (Solanum tuberosum, ssp. tuberosum) with RFLP-fingerprints. AB - The possibility of genotype identification with RFLP fingerprints was examined with 20 tetraploid potato varieties and 38 diploid potato lines. By using a sensitive detection system for small restriction fragment length differences and highly variable potato sequences as probes, all genotypes (diploids and tetraploids) were distinguished by a minimum of two probe/enzyme combinations. The best single probe/enzyme combination distinguished 19 out of 20 4n varieties and 33 out of 38 2n lines. Intravarietal variability was very small compared to the intervarietal variability, and patterns obtained with different DNA sources of the same genotype were identical. PMID- 24227025 TI - Alloplasmic male sterility in AD allotetraploid Gossypium hirsutum upon replacement of its resident A cytoplasm with that of D species G. harknessii. AB - Alloplasmic male sterile (cms) and restoration-of-fertility (Rf) lines of the AD allotetraploid Gossypium hirsutum were earlier derived from the presumed introgression of the cytoplasm of the D species G. harknessii. To confirm that this happened and address its significance, cytoplasms of the maternal progenitor, backcross intermediates, derived breeding lines, related A, D, and F species, and a synthetic AD tetraploid were examined by agarose and polyacrylamide gel electrophoresis of 140 restriction enzyme fragments of chloroplast DNA. Length mutations of 10-50 nucleotides predominate over site loss/gain mutations. Chloroplast DNA is maternally inherited and that of G. harknessii has been maintained in the cms lines for at least 13 successive generations without detectable alteration. Chloroplast DNA divergence is consistent with current nuclear genome classification and shows that the A progenitor was the maternal parent of the AD tetraploids. As predicted from incompatability models of cms, the degree of male sterility in alloplasmic Gossypium tetraploids is correlated with the extent of evolutionary divergence of their cytoplasms. It is suggested that the A genome in the AD tetraploids dominates those nuclear-cytoplasm interactions reflected by male fertility. PMID- 24227026 TI - Delivery of foreign genes to intact barley cells by high-velocity microprojectiles. AB - Foreign DNA was introduced through the cell walls of intact suspension culture cells of barley (Hordeum vulgare L.) by utilizing the particle acceleration approach. DNA-coated microscopic tungsten particles were accelerated to velocities that permitted their penetration of intact cells. Chimaeric constructs of beta-glucuronidase and neomycin phosphotransferase II under the control of the dual Agrobacterium TR 1'2' promoter or the cauliflower mosaic virus 35S promoter served as reporter genes. Three days after particle delivery, high-level expression of both reporter genes was observed. That plasmid size could be critical for stabilizing DNA in the course of particle delivery will be discussed. PMID- 24227027 TI - Somatic hybridization of sexually incompatible top-fruit tree rootstocks, wild pear (Pyrus communis var. pyraster L.) and Colt cherry (Prunus avium x pseudocerasus). AB - Mesophyll protoplasts of wild pear (Pyrus communis var. pyraster L., Pomoideae) were chemically fused with cell suspension protoplasts of cherry rootstock Colt (Prunus avium x pseudocerasus, Prunoideae), following an electroporation treatment of the separate parental protoplast systems. Fusion-treated protoplasts were cultured, on modified K8P medium, where it had been previously established that neither parental protoplasts were capable of division. Somatic hybrid calli were recovered and, following caulogenesis on MS medium with zeatin and after rooting of regenerated shoots, complete trees were obtained and grown in vivo. Hybridity of these trees was confirmed based on morphological characters, chromosome complement and isozyme analysis. Two separate cloned lines of this intersubfamilial rootstock somatic hybrid (wild pear (+) Colt cherry) were produced. This is the first report of the production of somatic hybrid plants of two woody species, of agronomic value, within the order Rosales. PMID- 24227028 TI - Hierarchical cluster analysis as a tool to manage variation in germplasm collections. AB - The potential of using hierarchical cluster analysis to classify entries from a germplasm collection according to their degree of similarity was assessed. Results suggest that similarity is generally greatest among individual entries by country of origin and that hierarchical cluster analysis could be used as a tool to classify entries from germplasm collections according to their respective gene pools, even when no passport data are available. Based on this technique, it is also shown that the segregative potential of entries can be estimated. PMID- 24227029 TI - Restriction fragment length polymorphism (RFLP) analyses of plants produced by in vitro anther culture of Solanum chacoense Bitt. AB - In this study, a novel approach was used to characterize the genetic architecture of plants produced by in vitro anther culture of two lines of self-incompatible Solanum chacoense Bitt. (2n=2x=24). We used cytological observations to determine the ploidy level of the regenerated plants and scanned genomic DNA of the anther donor plants to identify heterozygous sequences. Restriction fragment length polymorphism (RFLP) analyses permitted the visualization of DNA variations. Several heterozygous DNA markers were found within single anther donor plants. Completely homozygous lines could be easily identified. Somatically derived plants could be separated from diploid plants produced from 2n (unreduced) microspores. Our results demonstrate first division restitution (FDR) as the mechanism operating during the production of 2n microspores in one of our S. chacoense line. Potential applications of RFLP analyses for genetic mapping, identification of lethal alleles and quantitative trait loci (QTL) with haploid or homozygous diploid plants and determination of gene-centromere distance with diploid plants derived from 2n microspores will be discussed. PMID- 24227030 TI - Use of tissue culture to bypass wheat hybrid necrosis. AB - Hybrid necrosis in wheat is a barrier to gene transfer in wheat breeding practice. It is based on two complementary genes, Ne1 and Ne2. Recovery mutants (Re1, Re2 and Re3) which can grow to maturity were recovered from immature embryo cultures of necrotic hybrids between T. aestivum and T. durum. Cytological observation demonstrated that Re1 had 34 chromosomes instead of 35. This indicated that one of the chromosomes carrying the Ne genes was lost. Genetic study suggested that for Re1, the lost chromosome was chromosome 5B of the durum parental line. Re mutants are male sterile but can be maintained through a young ear culture method. Re mutants could be successfully pollinated by either parental line and the BC1 progeny is partially fertile. Re mutants were repeatedly induced in about 1% of the regenerated plants from immature embryo culture. This technique provides a practical way to bypass hybrid necrosis. PMID- 24227031 TI - Comparison of unpredictable environmental variation generated by year and by seeding-time factors for measuring type 4 stability. AB - Type 4 stability has been proposed to measure a cultivar's homeostatic property to resist unpredictable environmental variation. The requirement for calculating this stability is that the experiment must contain a time factor in addition to the cultivar x location factors. Of the two time factors, year and seeding-time, the latter is less attractive biologically because it represents only a part of the broader context of unpredictable variation represented by years, but it is attractive in terms of shortening the test period. Investigation of historical data from the Eastern Cooperative trials and the Ontario Production trials in Canada indicates that the unpredictable variation generated by seeding-time was about half that generated by year. Although type 4 stability measured by both factors appears to be the same, the stability measured by seeding-time is more prone to variation. The implication is that complete substitution of the year factor by seeding-time is not appropriate, but use of both factors in combination may be sensible. PMID- 24227032 TI - RFLP analysis and linkage mapping in Solanum tuberosum. AB - A morphologically and agronomically heterogeneous collection of 38 diploid potato lines was analysed for restriction fragment length polymorphisms (RFLPs) with 168 potato probes, including random genomic and cDNA sequences as well as characterized potato genes of known function. The use of four cutter restriction enzymes and a fragment separation range from 250 to 2,000 bases on denaturing polyacrylamide gels allowed the detection of RFLPs of a few nucleotides. With this system, 90% of all probes tested showed useful polymorphism, and 95% of those were polymorphic with two or all three enzymes used. On the average, 80% of the probes were informative in all pairwise comparisons of the 38 lines with a minimum of 49% and a maximum of 95%. The percentage of heterozygosity was determined relative to each other for each line and indicated that direct segregation analysis in F1 populations should be feasible for most combinations. From a backcross involving one pair of the 38 lines, a RFLP linkage map with 141 loci was constructed, covering 690 cMorgan of the Solanum tuberosum genome. PMID- 24227033 TI - A BamHI family of highly repeated DNA sequences of Nicotiana tabacum. AB - HRS60.1, a monomer unit (184 bp) of a highly repeated nuclear DNA sequence of Nicotiana tabacum, has been cloned and sequenced. Following BamHI digestion of tobacco DNA, Southern hybridization with HRS60.1 revealed a ladder of hybridization bands corresponding to multiples of the basic monomer unit. If the tobacco DNA was digested with restriction endonucleases which have no target site in HRS60.1, the larger part of DNA homologous to HRS60.1 remained as uncleaved "relic" DNA. These results suggest a tandem arrangement of this DNA repeat unit. Four other clones of tobacco nuclear DNA cross-hybridized with HRS60.1, thus forming a "HRS60-family". Sequencing their inserts has shown their strong mutual homology. HRS60-family comprised about 2% of the nuclear genome of N. tabacum. Computer comparisons with other tandem plant-repeated DNA sequences could not detect any other homologous sequence. PMID- 24227034 TI - Isolation and characterization of streptomycin-resistant mutants in Nicotiana plumbaginifolia. AB - Streptomycin-resistant colonies were isolated from protoplast cultures of haploid Nicotiana plumbaginifolia based on their ability to green in medium containing 1 mg/ml streptomycin sulfate. The frequency of resistant colonies was 0.9*10(-5) in nonmutagenized culture, and increased ten-fold following treatment of culture with 10 MUg/ml N-methyl-N'-nitro-N-nitrosoguanidine. Of a total of 52 resistant clones isolated, 2 gave rise to haploid, 15 to diploid, and 3 to tetraploid plants upon transfer of calli to differentiation medium. Leaf-segment and protoplast assays showed that all diploid regenerates were resistant to streptomycin but sensitive to chloramphenicol, kanamycin, lincomycin, neomycin, and spectinomycin. Plants in most diploid clones were fertile and able to set seeds when self-fertilized and crossed reciprocally to wild-type plants. Inheritance of streptomycin resistance was studied in the diploid clones and, without exception, the resistance was transmitted maternally. Comparative studies of the ultrastructure of organelles and protein synthesis in isolated chloroplasts between wild-type and resistant clones in the presence of streptomycin suggest that streptomycin resistance is controlled by chloroplasts. PMID- 24227035 TI - Selection strategies and artificial evolution. AB - Artificial selection results in biolgical changes, creating artificial evolution. When using selection indexes, the artificial evolution depends on the relative economic (or other) weight of traits in the breeding objective, and on the phenotypic and genetic variances and covariances among these traits and the traits recorded in the selection index. As shown here, the selection strategy (in this case, individual selection versus progeny test selection) can also have marked effects on the kind of artificial evolution produced. Thus, where economic weights are uncertain, choice between alternative selection strategies might take into account the different types of animal or plant resulting. PMID- 24227036 TI - Localization of the alpha2-macroglobulin gene and Lpm gene family on mink chromosome 9. AB - Using cloned cDNA for human alpha2-macroglobulin (A2M) as a probe, mink-Chinese hamster hybrid cells were analysed. The results allowed us to assign a gene for A2M to mink chromosome 9. Breeding tests demonstrated that the Lpm-locus coding for other related alpha-macroglobulin protein and the gene for peptidase B (PEPB) are linked 11+/-3 cm apart. The PEPB gene is located on mink chromosome 9, and hence, the Lpw-locus is on the same mink chromosome. The relationship of the genetic systems controlling the isotypically different alpha-macroglobulins in mink serum are discussed. PMID- 24227037 TI - Genetical control and linkage relationships of isozyme markers in sugar beet (B. vulgaris L.) : 1. Isocitrate dehydrogenase, adenylate kinase, phosphoglucomutase, glucose phosphate isomerase and cathodal peroxidase. AB - Five isozyme systems were genetically investigated. The different separation techniques, the developmental expression and the use as marker system in sugar beet genetics and breeding is discussed. Isocitrate dehydrogenase was controlled by two genes. The gene products form inter- as well as intralocus dimers, even with the gene products of the Icd gene in B. procumbens and B. patellaris. Adenylate kinase was controlled by one gene. Three different allelic forms were detected, which were active as monomeric proteins. Glucose phosphate isomerase showed two zones of activity. One zone was polymorphic. Three allelic variants, active as dimers, were found. Phosphoglucomutase also showed two major zones of activity. One zone was polymorphic and coded for monomeric enzymes. Two allelic forms were found in the accessions studied. The cathodal peroxidase system was controlled by two independent genes, of which only one was polymorphic. The gene products are active as monomers. Linkage was found between red hypocotyl color (R) and Icd 2. Pgm 1, Gpi 2, Ak 1 and the Icd 2-R linkage group segregated independently. PMID- 24227038 TI - Plant regeneration and variants from calli derived from immature embryos of diploid barley (Hordeum vulgare L.) and H. vulgare L. x H. bulbosum L. crosses. AB - Plant regeneration from calli was carried out at two locations using several parental genotypes and environments. Selfed immature diploid (VV) barley (Hordeum vulgare) embryos and immature haploid (V) or hybrid (VB) embryos from crosses between H. vulgare and H. bulbosum were used as explants. 'Golden Promise', 'Emir' and 'CB 7432' were the best cultivars for plant regeneration, and 15 degrees C tended to be more suitable for plant development than higher temperatures. A total of 844 regenerants were obtained, and over 200 fertile progenies were screened agronomically. Apart from the occurrence of polyploidy and albinism, three variants were identified. One showed maternal inheritance for yellow leaf striping while the other two were controlled by single recessive genes. One of these possessed increased resistance to scald (Rhynchosporium secalis) compared with the donor parent cv 'Triumph', and one resembled a chlorina mutant. PMID- 24227039 TI - Effect of repeated DNA sequences on direct gene transfer in protoplasts of Nicotiana plumbaginifolia. AB - Highly repeated nuclear DNA sequences from leaves of Nicotiana plumbaginifolia were cloned in pBR322 and tested for their effect on direct gene transfer in protoplasts of the same organism. Protoplasts were prepared from suspension cultures and were incubated in the presence of the plasmid pHP23 carrying the kanamycin resistance gene APH(3')II and in the presence of the plasmids carrying the cloned sequence. DNA uptake was induced by a polyethyleneglycol (PEG) treatment. Out of the 22 tested clones, 3 significantly stimulated the frequency of appearance of transformed colonies. DNA was extracted from some of the kanamycin-resistant calli obtained by co-transformations. Dot-blots have shown that the stimulatory effect on transformation frequency is often accompanied by a consistent increase in integrated genes sequences. PMID- 24227040 TI - Genetic diversity in Cucumis sativus L. assessed by variation at 18 allozyme coding loci. AB - The genetic diversity of the U.S. Cucumis sativus L. germplasm collection [757 plant introductions (PI) representing 45 countries] was assessed using 40 enzymes which represented 74 biochemical loci. Polymorphisms were observed at 18 loci (G2dh-1, Gpi-1, Gpi-2, Gr-1, Gr-2, Idh, Mdh-1, Mdh-2, Mdh-3, Mpi-2, Pepla-2, Peppap-2, Per-4, Pgd-1, Pgd-2, Pgm-1, Pgm-3, and Skdh). Two PIs (285606 and 215589) contained alleles [G2dh-1(1) and Per-4(2), respectively] which did not occur in any other PI. Other alleles which occurred in low frequencies (in < 1% of the PIs) included Gpi-1(3), Gpi-2(3), Gr-1(3), Gr-2(1), Idh(1), Mdh-1(2), Mdh 2(1), Peppap-2(1), and Pgd-1(1). Individual loci containing more than one allele in greater than 20% of the PIs included Mpi-2, Pepla-2, Pgd-2, and Pgm-1. Multivariate analyses aided in the reduction of data (principle components), depicted relationships among PIs (cluster), and identified the most discriminating enzyme loci (Pgm-1, Pepla-2, Gr-1, Pgd-2, Mpi-2, and Skdh) (classification and regression tree). PMID- 24227041 TI - The mentor pollen phenomenon in poplars: a new concept. AB - The mentor effect has been investigated in poplars. Attempts to overcome interspecific incompatibility are analysed by pollen germination and pollen tube behaviour in situ, both for compatible and incompatible crosses. We have demonstrated that following the mixed pollination, the two pollen sets interact at different levels of the progamic phase. A hypothetical model is proposed which describes mentor effect as the result of interactions of antagonist and cynergic forces applying on compatible pollen and tubes. These forces promote pollen tube growth both on the female partner surface and within the tissues. PMID- 24227042 TI - Inheritance of somatic embryogenesis and organ regeneration from immature embryo cultures of winter wheat. AB - Diallel analyses of F1 and reciprocal crosses among five winter wheat lines show that additive, non-additive, and cytoplasmic genetic effects were significant in the genetic control of somatic embryogenesis, shoot, and root induction frequencies as well as in numbers of somatic embryos, shoots, and roots. However, additive genetic effect appears to be most important since, in most cases a larger portion of the cross variation was accounted for by general combining ability. The results suggest that somatic embryogenesis and organ regeneration in winter wheat can be improved through genetic manipulation. Due to the presence of maternal effects, it may be critical to use a suitable genotype as a female parent in a selection program. PMID- 24227043 TI - Inheritance of seed dormancy in Cummis sativus var. hardwickii (Royle) Alef. AB - Reciprocal matings were made between two Cucumis sativus var. sativus L. inbred lines (WI 1606 and WI 2808) and two var. hardwickii (Royle) Alef. accessions (PI 215589 and PI 183967). Each case produced a series of reciprocal F1, F2, and BC1 and BC2 progenies which were used to evaluate seed dormancy in var. hardwickii. Under controlled conditions (25 degrees +/-1 degrees C and 85%+/-5% RH; 12 h fluorescent light, 30 MUmol s(-1) m(-2)), no seed dormancy was observed in the var. sativus inbred lines 36 days following seed extraction from fruit. With rare exception, var. hardwickii accessions were dormant for at least 60 days. Seed dormancy in the F1 was absent 36 days post extraction, indicating that dormancy in var. hardwickii is conditioned by recessive genes present. Seed of some F1 progeny germinated between 36 and 50 days post-extraction, indicating the presence of transient dormancy or the more variable expression of the dormancy of var. hardwickii. No significant reciprocal differences in either germination rate or percentage were detected in either of the F1 and F2 progeny sets, suggesting lack of cytoplasmic or maternal control over these traits. It was estimated that three to seven factors or loci are involved with the expression of this trait depending on the method of calculation, and that a complex interaction between embryonic and non-embryonic tissue exists. Least square estimates indicate that both additive and dominance effects were important in the expression of dormancy. Comparison of theoretical geometric and arithmetic F2 means to observed F2 means also suggests that non-additive gene action contributes substantially to the observed variation. Broad-sense heritability ranged between 78 and 95%. PMID- 24227044 TI - Alternative male reproductive tactics drive asymmetrical hybridization between sunfishes (Lepomis spp.). AB - The potential role of alternative reproductive tactics in circumventing premating isolating mechanisms and driving hybridization between species has long been recognized, but to date there is little empirical support from natural systems. Hybridization occurs between bluegill (Lepomis macrochirus) and pumpkinseed sunfish (Lepomis gibbosus) and it is known to be asymmetrical (male bluegill * female pumpkinseed). Here, we test whether this pattern is driven by a recognition failure by pumpkinseed females or by an alternative cuckolder reproductive tactic in bluegill males. Using genetic parentage data, we found that bluegill cuckolders fathered 24.9% of the larvae in bluegill nests, but no evidence that pumpkinseed females spawned in bluegill nests. Pumpkinseed cuckolders fathered 8.7% of the larvae in pumpkinseed nests, whereas bluegill cuckolders fathered 13.6% of the larvae in those nests. Bluegill cuckolders thus frequently spawn in pumpkinseed nests and are responsible for the asymmetrical hybridization between the species. We discuss the evolutionary consequences of interactions between bluegill and pumpkinseed and the role of alternative reproductive tactics in adaptation and introgression. PMID- 24227045 TI - Evidence for a recent origin of penguins. AB - Penguins are a remarkable group of birds, with the 18 extant species living in diverse climatic zones from the tropics to Antarctica. The timing of the origin of these extant penguins remains controversial. Previous studies based on DNA sequences and fossil records have suggested widely differing times for the origin of the group. This has given rise to widely differing biogeographic narratives about their evolution. To resolve this problem, we sequenced five introns from 11 species representing all genera of living penguins. Using these data and other available DNA sequences, together with the ages of multiple penguin fossils to calibrate the molecular clock, we estimated the age of the most recent common ancestor of extant penguins to be 20.4 Myr (17.0-23.8 Myr). This time is half of the previous estimates based on molecular sequence data. Our results suggest that most of the major groups of extant penguins diverged 11-16 Ma. This overlaps with the sharp decline in Antarctic temperatures that began approximately 12 Ma, suggesting a possible relationship between climate change and penguin evolution. PMID- 24227046 TI - Oxytocin shapes parental motion during father-infant interaction. AB - An infant-oriented parental repertoire contributes to an infant's development and well-being. The role of oxytocin (OT) in promoting affiliative bonds and parenting has been established in numerous animal and human studies. Recently, acute administration of OT to a parent was found to enhance the carer's, but at the same time also the infant's, physiological and behavioural readiness for dyadic social engagement. Yet, the exact cues that are involved in this affiliative transmission process remain unclear. The existing literature suggests that motion and vocalization are key social signals for the offspring that facilitates social participation, and that distance and motion perception are modulated by OT in humans. Here, we employed a computational method on video vignettes of human parent-infant interaction including 32 fathers that were administered OT or a placebo in a crossover experimental design. Results indicate that OT modulates parental proximity to the infant, as well as the father's head speed and head acceleration but not the father's vocalization during dyadic interaction. Similarly, the infant's OT reactivity is positively correlated with father's head acceleration. The current findings are the first to report a relationship between the OT system and parental motion characteristics, further suggesting that the cross-generation transmission of parenting in humans might be underlaid by nuanced, infant-oriented, gestures relating to the carer's proximity, speed and acceleration within the dyadic context. PMID- 24227047 TI - Action at a distance: dependency sensitivity in a New World primate. AB - Sensitivity to dependencies (correspondences between distant items) in sensory stimuli plays a crucial role in human music and language. Here, we show that squirrel monkeys (Saimiri sciureus) can detect abstract, non-adjacent dependencies in auditory stimuli. Monkeys discriminated between tone sequences containing a dependency and those lacking it, and generalized to previously unheard pitch classes and novel dependency distances. This constitutes the first pattern learning study where artificial stimuli were designed with the species' communication system in mind. These results suggest that the ability to recognize dependencies represents a capability that had already evolved in humans' last common ancestor with squirrel monkeys, and perhaps before. PMID- 24227048 TI - Brains and the city in passerine birds: re-analysis and confirmation of the original result. PMID- 24227049 TI - Chronology of fusion of the primary and secondary ossification centers in the human sacrum and age estimation in child and adolescent skeletons. AB - Little is known about fusion times of the primary and secondary centers of ossification in the sacrum, particularly from dry bone observations. In this study, the timing of union of these centers was studied in a sample of modern Portuguese skeletons (90 females and 101 males) between the ages of 0 and 30 years, taken from the Lisbon documented skeletal collection. A three-stage scheme was used to assess fusion status between ossification centers as unfused, partially fused and completely fused. Posterior probability tables of age, given a certain stage of fusion, were calculated for most anatomical locations studied using both reference and uniform priors. Partial union of primary centers of ossification was observed from 1 to 8 years of age and partial union of secondary centers of ossification was observed from 15 to 21 years of age. The first primary centers of ossification to complete fusion are the neural arch with the centrum of the fifth sacral vertebrae and the last are the costal element with the centrum of the first sacral vertebra. The annular and sacroiliac epiphyses are the first, among the secondary centers of ossification observed, to complete fusion, after which the lateral margin fuses. This study offers information on timing of fusion of diverse locations in the developing sacrum useful for age estimation of complete or fragmented immature human skeletal remains and fills an important gap in the literature, by adding to previously published times of fusion of primary and secondary ossification centers in this sample. PMID- 24227050 TI - Isomerization and decomposition of a Criegee intermediate in the ozonolysis of alkenes: dynamics using a multireference potential. AB - The isomerization and decomposition dynamics of the simplest Criegee intermediate CH2 OO have been studied by classical trajectory simulations using the multireference ab initio MR-PT2 potential on the fly. A new, accelerated algorithm for dynamics with MR-PT2 was used. For an initial temperature of 300 K, starting from the transition state from CH2 OO->CH2 O2 , the system reaches the dioxirane structure in around 50 fs, then isomerizes to formic acid (in ca. 2800 fs), and decomposes into CO+H2 O at around 2900 fs. The contributions of different configurations to the multiconfigurational total electronic wave function vary dramatically along the trajectory, with diradical contributions being important for transition states corresponding to H-atom transfers, while being only moderately significant for CH2 OO. The implications for reactions of Criegee intermediates are discussed. PMID- 24227052 TI - Embryogenesis and plant regeneration from anther culture of bamboo (Sinocalamus latiflora (Munro) McClure). AB - Embryogenic callus was initiated from bamboo (Sinocalumus satiflora (Munro) McClure) anthers cultured on N6 medium supplemented with 1 mg/l 2,4-D, 1 mg/l BA, 2 g/l charcoal, 0.8% agar (Sigma) and 9% sucrose. Anthers with microspores at miduninucleate to early-binucleate stages showed better rate of response for callus induction. Prolonged culture of these embryogenic calli on the original medium or subculture to an auxin-free medium resulted in embryoid formation and their subsequent germination to form rooted plantlets. Chromosome counts from root-tip cells of anther-derived plant indicated that they were haploid (N=36). PMID- 24227051 TI - Socioeconomic inequalities in all-cause mortality in the Czech Republic, Russia, Poland and Lithuania in the 2000s: findings from the HAPIEE Study. AB - BACKGROUND: Relatively large socioeconomic inequalities in health and mortality have been observed in Central and Eastern Europe (CEE) and the former Soviet Union (FSU). Yet comparative data are sparse and virtually all studies include only education. The aim of this study is to quantify and compare socioeconomic inequalities in all-cause mortality during the 2000s in urban population samples from four CEE/FSU countries, by three different measures of socioeconomic position (SEP) (education, difficulty buying food and household amenities), reflecting different aspects of SEP. METHODS: Data from the prospective population-based HAPIEE (Health, Alcohol, and Psychosocial factors in Eastern Europe) study were used. The baseline survey (2002-2005) included 16 812 men and 19 180 women aged 45-69 years in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Data were analysed by direct standardisation and Cox regression, quantifying absolute and relative SEP differences. RESULTS: Mortality inequalities by the three SEP indicators were observed in all samples. The magnitude of inequalities varied according to gender, country and SEP measure. As expected, given the high mortality rates in Russian men, largest absolute inequalities were found among Russian men (educational slope index of inequality was 19.4 per 1000 person-years). Largest relative inequalities were observed in Czech men and Lithuanian subjects. Disadvantage by all three SEP measures remained strongly associated with increased mortality after adjusting for the other SEP indicators. CONCLUSIONS: The results emphasise the importance of all SEP measures for understanding mortality inequalities in CEE/FSU. PMID- 24227053 TI - Regulation of alpha-amylase promoter by gibberellic acid and abscisic acid in barley protoplasts transformed by electroporation. AB - Transient gene expression was studied in isolated protoplasts of barley (Hordeum vulgare L. cv Himalaya) transformed by electroporation. Two plasmid constructions were used, both of which contained the gene coding for neomycin phosphotransferase II (nptII) as a reporter gene. In one plasmid the reporter gene was under the control of an alpha-amylase group 1 gene promoter of barley and in the other, used as a control, under the CaMV 35S transcript promoter. Protoplasts were isolated from three different types of tissue: the aleurone layer, the scutellar epithelium and the mesophyll. All three types of protoplasts electroporated with 35S -nptII plasmid construction showed strong NPTII activity on which GA3 and ABA had no effect. In protoplasts isolated from the aleurone layer and scutellum the expression of amy-nptII was low when compared with the expression of 35S -nptII. In aleurone protoplasts GA3 enhanced the expression of amy-nptII about tenfold and ABA prevented the action of GA3. In protoplasts isolated from the scutellar epithelium GA3 did not affect the low level of expression of amy-nptII. In mesophyll protoplasts the amy-nptII was not expressed at all. PMID- 24227054 TI - Optimizing sweet potato [Ipomoea batatas (L.) Lam.] root and plantlet formation by selection of proper embryo developmental stage and size, and gel type for fluidized sowing. AB - Potassium starch polyacrylamide, potassium acrylate, a copolymer of potassium acrylate and acrylamide, and hydroxyethylcellulose carrier gels were tested to find a fluid drilling material suited for synthetic seeding of sweet potato (Ipomoea batatas (L.) Lam.) somatic embryos. Somatic embryo developmental stage and size, and maturation (incubation) time were also evaluated to improve plantlet formation. All embryos suspended in the fluidized hydroxyethylcellulose gel were viable after six days and 7% developed into plantlets after two weeks. Up to 97% of the somatic embryos suspended in acrylate and/or acrylamide gels died within six days. Root development was at least 10% and plantlet development at least 30% greater when embryos were subcultured on basal medium for 16 instead of 25 days prior to placement and suspension in hydroxyethylcellulose gel. Up to 25% more plantlets were obtained from embryos at the elongated torpedo stage than those at the cotyledonary or torpedo stages of development. When suspended in hydroxyethylcellulose gel embryo length had no effect on the percentage of plantlets obtained. PMID- 24227055 TI - Agrobacterium induced gall formation in bell pepper (Capsicum annuum L.) and formation of shoot-like structures expressing introduced genes. AB - The objective of this research was to define an in vitro regeneration and transformation system for bell pepper (Capsicum annuum L.) using six cultivars and one Guatemalan wild accession. The wild accession exhibited the best regeneration response. Only occasional elongation of shoot buds in 'Yolo Wonder L' was achieved by culture in the dark on a medium containing 10 mg/l BA and l mg/l IAA. Transformed shoot buds and leaf-like structures were obtained, showing beta- glucuronidase activity predominantly in the vascular and perivascular tissues, with no indication of contaminating Agrobacterium in the tissues. Attempts to regenerate whole transgenic plants from transformed shoot buds were unsuccessful. PMID- 24227056 TI - Improved embryoid induction and green shoot regeneration from wheat anthers cultured in medium with maltose. AB - Anthers from spring wheat (Triticum aestivum L.) genotypes, including six F1 hybrids, were cultured in a modified liquid N6 medium containing either sucrose or maltose. In every case, use of maltose resulted in greater microspore callus induction and green shoot regeneration than culture in sucrose-containing medium. Induction in maltose medium also allowed green shoots to be recovered from crosses that showed only a poor response in other media and from two genotypes that did not respond to modified N6 medium with sucrose. Replacement of sucrose with maltose generally resulted in microspores having a more embryogenic mode of development in which distinct embryoids often formed. The most responsive genotype produced over 200 green shoots/100 anthers when cultured in medium with maltose. PMID- 24227057 TI - Shoot regeneration from stem and leaf callus of Eucalyptus tereticornis. AB - Adventitious shoots were obtained from leaf and stem callus of Eucalyptus tereticornis SM. Callus was induced on B5 medium with 0.1 mg/l benzyladenine (BA) and 3 or 5 mg/l naphthalene acetic acid in the dark. Shoot initiation occurred on modified Woody Plant medium (mWP) containing 0.5 mg/l BA, 500 mg/l polyvinylpyrrolidone and 10% (v/v) coconut milk. Multiple shoots were also regenerated directly from hypocotyl segments of 4 to 6 week old seedlings on B5 medium with 0.5 mg/l BA. Regenerated shoots could be rooted with 100% efficiency on mWP medium containing 0.5 mg/l indolebutyric acid and transferred to soil in the greenhouse. Suspension cultures were obtained from the callus using B5 medium with 0.5 mg/l 2,4-dichlorophenoxyacetic acid. Callus clumps grew from less than 1 mm to 4-6 mm in diameter within two weeks on transfer to shoot regeneration medium but failed to form shoots or somatic embryos. PMID- 24227058 TI - Air pollutants from hydrocarbons and derivatives in micropropagation laboratories: toxicity symptoms on tissue culture of the cherry rootstock Colt (Prunus avium x P. pseudocerasus). AB - Several air pollutants in research and micropropagation laboratories originate from the combustion of hydrocarbons and their derivatives. The combustion products of some natural gases (propane-butane, propane, methane) and ethanol were analyzed, and the atmosphere composition was investigated inside the laminar flow box, inside the room where transplanting is performed and inside the culture vessels after transplanting. Large quantities of ethylene and other biologically active compounds are produced when hydrocarbons are partially oxidized or unevenly combusted and when ethanol is used for sterilization of dissecting instruments during transplanting operations. Air pollutants' effects have been tested on Prunus Colt shoot cultures; the toxicity symptoms observed suggest the elimination of gas combustion and alcohols during transplanting operations. PMID- 24227059 TI - Selection of penstemide and serrulatoloside producing clones in penstemon serrulatus by small-aggregate cloning. AB - A plating method is described for cultured cells of Penstemon serrulatus Menz. which allows effective cloning of aggregates consisting of less than 10 cells, on a simple synthetic medium. The obtained clones snowed high diversity with respect to their ability to produce penstemide, an ester iridoid of the Valeriana-type. Some of the clones produced higher quantities of this compound than the original cell line. The content of another iridoid glucoside of the same type, serrulatoloside, was also determined. PMID- 24227060 TI - Production of tumour-inhibitory lignans in callus cultures of Podophyllum hexandrum. AB - Callus cultures have been established from root explants of aseptically-grown Podophyllum hexandrum seedlings. A fully defined medium based on Gamborg's B5 salts supplemented with 2/4-dichlorophenoxyacetic acid, gibberellic acid and 6 benzylaminopurine was effective for both initiation and sustained growth of callus tissue. Cultures produced anticancer lignans podophyllotoxin, 4' demethylpodophyllotoxin and podophyllotoxin 4-O-glucoside at levels similar to those found in the expiant material as assayed by high performance liquid chromatography. The relative proportions of podophyllotoxin and 4'-demethyl podophyllotoxin were markedly influenced by the presence of plant growth regulators. Particularly high levels of podophyllotoxin were associated with growth regulator induced tissue differentiation. PMID- 24227061 TI - Competence for gene transfer by electroporation in a sub-population of protoplasts from uniform carrot cell suspension cultures. AB - We have investigated the basis for increased transient reporter gene expression following electroporation of protoplasts from uniform carrot cell suspension cultures at increasing DNA concentrations. Use of a combination of histochemical and fluorometric GUS gene assays allowed differentiation between increases due to a higher proportion of expressing protoplasts and increases due to higher expression by each expressing protoplast. A plateau of 20-25% expressing protoplasts was reached by 50 MUg ml(-1) DNA but total expression continued to increase in direct proportion to applied DNA concentration up to at least 100 MUg ml(-1). This indicates the existence of a subpopulation of protoplasts competent for the uptake and expression of genes by electroporation. PMID- 24227062 TI - Micropropagation of Phytolacca dodecandra through shoot-tip and nodal cultures. AB - A procedure for micropropagation of endod (Phytolacca dodecandra) is described. BA at 0.44 MUM produced 3.1 new shoots per expiant in six weeks using shoot tips. Nodal expiants, however, produced up to 4.7 shoots per explant on medium with 0.44 MUM BA and 0.27 MUM GA,. IBA at 0.49 MUM induced 90% rooting with minimal callus. Plantlets were successfully transferred to the greenhouse and some staminate clones produced flowers after six months. PMID- 24227063 TI - Production of nematocidal compounds by hairy root cultures of Tagetes patula L. AB - Marigold (Tagetes patula L.) hairy roots induced by infection with Agrobacterium rhizogenes produced alpha-terthienyl when grown in darkness, and an n-hexane extract of the roots showed nematocidal activity. Depending on the hairy root line used, the level of alpha-terthienyl varied from 15 to 1268 MUg per g dry weight, a level that corresponded to 0.15 to 12.7-fold that in intact roots. Analysis by HPLC indicated that the nematocidal activity was due predominantly to alpha-terthienyl. However, it is suggested that nematocidal compounds other than alpha-terthienyl are present in hairy roots cultured in the dark for long periods or in the light. PMID- 24227064 TI - Plant regeneration by somatic embryogenesis from cultured immature embryos of oak (Querem robur L.) and linden (Tilia cordata Mill.). AB - Embryogenic cultures and somatic embryos were obtained from immature zygotic embryos of oak (Quercus robur L.) cultured on a modified MS medium and WPM containing BAP (1 mg.l(-1)) and GA3 (1 mg.l(-1)) or BAP and IBA. Germination and conversion of oak somatic embryos into plantlets was achieved on WPM containing a reduced concentration of cytokinin. Linden (Tilia cordata Mill.) somatic embryos developed in embryogenic tissues initiated from immature zygotic embryos cultured on a modified MS medium supplemented with 2,4-D (0.3-2.0 mg.l(-1)). Germination of linden somatic embryos and plantlet formation occurred on MS medium containing a low concentration of IBA. Oak and linden plantlets produced from somatic embryos were successfully established in soil. Somatic embryos and plantlets were also regenerated from embryogenic cultures of Quercus petraea and Tilia platyphyllos. PMID- 24227065 TI - Plant regeneration from mesophyll protoplasts of Centaurea cyanus, Senecio x hybridus and Callistephus chinensis. AB - Protoplasts were isolated from leaves of glasshouse-grown plants of Centaurea cyanus and axenic shoot cultures of Senecio x hybridus. Upon culture, using modified MS-based media, protoplasts of both systems entered division to produce callus, followed by plant regeneration. Leaf protoplasts of Callistephus chinensis entered sustained division only following the preconditioning for 24h of peeled leaf tissues on agar-solidified MS-based medium. Protoplasts were also isolated from cell suspensions of C. chinensis and divided in MS-based or KM media. However, only leaf mesophyll protoplasts of Callistephus produced callus, which developed shoots.The establishment of protoplast-to-plant protocols for these ornamental species has provided a basis for broadening their gene pools through somatic hybridisation. PMID- 24227066 TI - Excision of the maize transposable element Ac in flax callus. AB - The frequency and fidelity of Ac transposition, and that of its non-autonomous derivative Ds, were investigated in flax callus. Flax (Linum usitatissimum var. Antares) hypocotyls were transformed with Agrobacterium Ti plasmid vectors containing the Ac or Ds element inserted within the untranslated leader sequence of a chimaeric neomycin phosphotransferase II gene. Kanamycin resistant tissues were produced as a result of excision of Ac in around 35% of the total number of Ac-containing transformants. In contrast, no excision was observed from transformants containing the Ds element. Whilst Ac appears to have excised completely from T-DNAs, little evidence was found to infer reintegration of the Ac element into the genome. PMID- 24227067 TI - The accumulation of podophyllotoxin-beta-D-glucoside by cell suspension cultures derived from the conifer Callitris drummondii. PMID- 24227068 TI - In vitro hepatic monodeiodination of L-thyroxine and the temporal effect of 17beta-estradiol on deiodination in rainbow trout (Salmo gairdneri Richardson). AB - Thein vitro hepatic monodeiodination of L-thyroxine (T4) to triiodo-L-thyronine (T3) in rainbow trout (Salmo gairdneri) was found to be pH- and temperature dependent, and was related to the amount of homogenate in the reaction vessel, suggestive of an enzyme-regulated event. Dithiothreitol (DTT) introduced into the reaction medium stimulated T3 production in a dose-related manner, whilst 6n propyl-2-thiouracil (PTU) inhibited T3 production, also in a dose-related manner. The conversion was stimulated in the presence of light and depressed at buffer concentrations of less than 0.1 M.Prior treatment of fish with an intraperitoneal slow-release implant containing 17beta-estradiol (E2), at doses which are known to induce chronic mild elevations in plasma E2 levels, elicited a biphasic response to E2 as regards hepatic T3 production from T4 with a depression of T4 to T3 conversion evident within 1-2 days after implantation, and a subsequent stimulation of T3 production evident 56 days after, implantation. This increased hepatic deiodinase activity after chronic exposure to E2 at physiological doses was accompanied by a 3.5 fold increase in Vmax without a significant change in Km, suggesting the presence of an increased amount of the enzyme. PMID- 24227069 TI - Fundulus heteroclitus Gonadotropin(s) 2. Year-round husbandry of animals with active pituitaries and responsive follicles. AB - Mummichogs (Fundulus heteroclitus) were exposed to various regimens of temperature and photoperiod in order to develop a routine husbandry procedure so as to have throughout the year a population of reproductively healthy fish with a good quantity and quality of prematuration follicles (1.2-1.5 mm) suitable for carrying out homologous bioassays ofF. heteroclitus gonadotropin. During the fall and winter months, wild fish in the field all had regressed ovaries (gonadosomatic index <1). On the other hand, laboratory-maintained fish, with or without cold temperature (15 degrees C) and short photoperiod (10 h light/day) pretreatment, generally had sexually mature ovaries (GSI>10) when maintained on a warm temperature (25 degrees C) and long photoperiod (14 h light) protocol. Ovarian follicles retrieved from laboratory fish were responsive toF. heteroclitus pituitary extract stimulation, and underwent germinal vesicle breakdown normallyin vitro. Hence these ovarian follicles served well as a bioassay forF. heteroclitus gonadotropin even outside of the normal breeding season. The pituitary glands retrieved from laboratory fish in winter also retained high gonadotropic potencies, in terms of maturational and steroidogenic activities. Our results thus demonstrated that active gametogenesis in laboratory maintained fish can be extended five months beyond the end of the normal breeding season. Apparently,F. heteroclitus in Florida is potentially a continuous breeder when under favorable conditions, but has a reproductive quiescent period imposed upon it by some environmental stressor(s). Although the design of the present experiments did not determine the relative importance of nutritional factors, temperature, and photoperiod on the annual reproductive cycle ofF. heteroclitus, there are indications that diatary factors may play a much more dominant role in the reproductive cycle than previously recognized. PMID- 24227070 TI - The effect of feeding three anabolic steroids in different combinations on the growth, food conversion efficiency and protein and nucleic acid levels of liver, kidney, brain and muscle of mirror carp (Cyprinus carpio). AB - A study on the effect of three different anabolic-androgenic steroids on the growth, food conversion efficiency and nucleic acid contents of liver, kidney, brain and muscle of carp,Cyprinus carpio was undertaken. The three steroids, methyltestosterone (MT), ethylestrenol (EE) and oxandrolone (ON), were fed in different combinations at final concentrations of 5 or 6 mg/kg diet for 60 days. No effect on the growth was observed in any of the experimental groups. A decrease in the specific growth rate (11-21%) and food conversion efficiency (20 29%) was noted. Feeding of drugs increased the cranio-somatic and reno-somatic index in all except one group. Hepatosomatic (ON+MT) and viscero-somatic (ON+MT; EE+MT+ON) indices decreased. Protein increased and RNA/DNA decreased in only one group while a decrease in protein/DNA was observed in the liver of all experimental groups. RNA/DNA increased and protein/RNA decreased only in one group while no effect was seen in protein and protein/DNA contents in any of the treated kidneys. Proteins, protein/RNA and protein/DNA decreased in certain groups in brain tissue. In muscle, no effect was seen in proteins or protein/DNA. Protein/RNA decreased in all but one group while RNA/DNA was higher only in the group fed all the three steroids together. PMID- 24227071 TI - The fate of noradrenaline and adrenaline in the perfused cod spleen. AB - The time course of appearance of catecholamine metabolites was studied in the spleen of cod,Gadus morhua, during perfusion with radioactively labelled noradrenaline and adrenaline at 10 degrees C. The tlag for appearance of the metabolites ranged between 1.78 and 6.76 min after onset of perfusion for both amines, indicating a rapid disposition of catecholamines. Perfusion with noradrenaline resulted in mainly MOPEG, VMA and DOMA formation, while perfusion with adrenaline additionally resulted in MN formation. There was still formation of deaminated metabolites after denervation, which indicates an additional non neuronal site of deamination. It is concluded from the study that the fate of noradrenaline and adrenaline within the cod spleen depends on their affinities for the two uptake mechanisms and an extraneuronal site of deamination of great importance cannot be excluded. PMID- 24227072 TI - Species differences in the adrenergic responses of fish red cells: studies on whitefish, pikeperch, trout and carp. AB - The occurrence and pH dependence (pHe 7-8) of the adrenergic red cell responses of two salmonids, trout and whitefish, and a percinid, pikeperch were studied. These are all species that live in well-oxygenated waters. The responses were compared to those of carp, which tolerates oxygen-deficient waters.The adrenergic responses of trout and whitefish red cells were pronounced. In these species red cell swelling, the accumulation of sodium and chloride in the cell, and the increase in red cell oxygen content at atmospheric oxygen tension were maximal at pH 7.3. In contrast, pikeperch red cells responded to beta-adrenergic stimulation only at extracellular pH 7.1. In carp, the adrenergic response, occurring below extracellular pH 7.5, was small as compared to the two salmonids. In each case the onset of the adrenergic response coincided with the onset of the Root effect.The differences in the adrenergic responses between the two salmonids and pikeperch suggest that the occurrence of the adrenergic response is not directly related to the environmental oxygen requirements of the species, but may be linked to the activity pattern. PMID- 24227073 TI - The influence of the dietary carbohydrate: lipid ratio on the chronic toxicity of sodium pentachlorophenate to rainbow trout (Salmo gairdneri Richardson). AB - The influence of diets varying in carbohydrate: lipid ratio on the chronic toxicity of waterborne sodium pentachlorophenate (0 or 50 MUg NaPCP.l(-1)) to rainbow trout (Salmo gairdneri) was examined over a 12 week period. The three diets used were practical salmonid formulations, equivalent in energy and protein content, with cerelose: fish oil ratios of 18.2?4.7% (high carbohydrate, HC), 9.3?9.1% (intermediate, INT), and 0.6?13.8% (low carbohydrate, LC). With increasing levels of dietary carbohydrate trout exhibited enlarged livers, elevated liver glycogen content, reduced liver protein content, reduced body lipid content, reduced weight gain, and elevated feed: gain ratio. For all diet groups, exposure of trout to NaPCP resulted in reduced liver glycogen content, higher liver protein content, reduced levels of plasma total triiodo-L-thyronine and L-thyroxine, increased thyroid epithelial cell height, and increased feed: gain ratios relative to their respective dietary control group. NaPCP exposure led to nominal reductions in weight gain and body lipid content of fish reared on the HC and INT diets. NaPCP exposed fish on the LC diet gained significantly less weight but had a higher body lipid content than control fish. The increasing NaPCP bioconcentration factor (BCF) associated with increasing lipid content of fish (log BCF=2.75 [log % lipid] +0.30; r=0.95) may explain the differences in response. Correction of bioconcentration data for the lipid content of fish reduced the range in BCF from 5- to 2.8-fold. PMID- 24227074 TI - Lactate dehydrogenase isozymes in the trunk and cardiac muscles of an antarctic teleost fish,Notothenia neglecta Nybelin. AB - The distribution and kinetics of lactate dehydrogenase (LDH) isozymes in the red and white trunk muscles, and cardiac muscle of an antarctic teleost fish (Notothenia neglecta Nybelin) have been studied. Pyruvate inhibition of LDH in all three muscle types is very low, being less than 50% even at a concentration of 60mM pyruvate. Activity versus pyruvate concentration profiles are not significantly different for LDH in all three muscle types. The Michaelis constant (Km) for pyruvate was not significantly different for all three LDH's. Raising the assay temperature caused an increase in Km of similar form in all three muscle types, while Km was lowest at the lowest assay temperature (-1 degrees C). When samples were run on a polyacrylamide gel, the bands stained specifically for LDH activity appeared at identical positions as those of the H2M2 band of the standards.It would appear therefore that the LDH isozyme found in the red and white trunk muscle ofN. neglecta is identical to that in cardiac muscle. This fact is discussed in relation to the physiological ecology of antaretic fishes, and the metabolic constraints imposed by their habitat, including their apparent low capacity for utilising glycolytic fuels. PMID- 24227075 TI - Referees of articles submitted to the journal in 1988. PMID- 24227076 TI - Thyroidal compensation in rainbow trout (Salmo gairdneri) fed canola meal. PMID- 24227077 TI - Anti-Mullerian hormone: reality check. PMID- 24227079 TI - Semiclassical approach to fluorescence spectra of polar dye solutions. Anharmonic approximation. AB - On the basis of the quasi-molecule model of electronic spectra of polar dye solutions, a description of structureless fluorescence spectra is accomplished. In the model, parameters of the spectrum have a simple physical interpretation and allow us to specify the dye-solvent interaction potentials in the initial and final states of fluorescence. These parameters for a few coumarin solutions are found by fitting theoretical distributions to the experimentally obtained spectra. A whole fluorescence spectrum can be theoretically reproduced only when the anharmonicity of the motion of molecules in solution is taken into account. However, a main part of the spectrum can also be recovered in harmonic approximation. A criterion for the fitting range in this case is formulated. PMID- 24227078 TI - Barcode tagging of human oocytes and embryos to prevent mix-ups in assisted reproduction technologies. AB - STUDY QUESTION: Is the attachment of biofunctionalized polysilicon barcodes to the outer surface of the zona pellucida an effective approach for the direct tagging and identification of human oocytes and embryos during assisted reproduction technologies (ARTs)? SUMMARY ANSWER: The direct tagging system based on lectin-biofunctionalized polysilicon barcodes of micrometric dimensions is simple, safe and highly efficient, allowing the identification of human oocytes and embryos during the various procedures typically conducted during an assisted reproduction cycle. WHAT IS KNOWN ALREADY: Measures to prevent mismatching errors (mix-ups) of the reproductive samples are currently in place in fertility clinics, but none of them are totally effective and several mix-up cases have been reported worldwide. Using a mouse model, our group has previously developed an effective direct embryo tagging system which does not interfere with the in vitro and in vivo development of the tagged embryos. This system has now been tested in human oocytes and embryos. STUDY DESIGN, SIZE, DURATION: Fresh immature and mature fertilization-failed oocytes (n = 21) and cryopreserved day 1 embryos produced by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 205) were donated by patients (n = 76) undergoing ARTs. In vitro development rates, embryo quality and post-vitrification survival were compared between tagged (n = 106) and non-tagged (control) embryos (n = 99). Barcode retention and identification rates were also calculated, both for embryos and for oocytes subjected to a simulated ICSI and parthenogenetic activation. Experiments were conducted from January 2012 to January 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Barcodes were fabricated in polysilicon and biofunctionalizated with wheat germ agglutinin lectin. Embryos were tagged with 10 barcodes and cultured in vitro until the blastocyst stage, when they were either differentially stained with propidium iodide and Hoechst or vitrified using the Cryotop method. Embryo quality was also analyzed by embryo grading and time-lapse monitoring. Injected oocytes were parthenogenetically activated using ionomycin and 6-dimethylaminopurine. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst development rates of tagged (27/58) and non-tagged embryos (24/51) were equivalent, and no significant differences in the timing of key morphokinetic parameters and the number of inner cell mass cells were detected between the two groups (tagged: 24.7 +/- 2.5; non-tagged: 22.3 +/- 1.9), indicating that preimplantation embryo potential and quality are not affected by the barcodes. Similarly, re-expansion rates of vitrified-warmed tagged (19/21) and non-tagged (16/19) blastocysts were similar. Global identification rates of 96.9 and 89.5% were obtained in fresh (mean barcode retention: 9.22 +/- 0.13) and vitrified warmed (mean barcode retention: 7.79 +/- 0.35) tagged embryos, respectively, when simulating an automatic barcode reading process, though these rates were increased to 100% just by rotating the embryos during barcode reading. Only one of the oocytes lost one barcode during intracytoplasmic injection (100% identification rate) and all oocytes retained all the barcodes after parthenogenetic activation. LIMITATIONS, REASONS FOR CAUTION: Although the direct embryo tagging system developed is effective, it only allows the identification and traceability of oocytes destined for ICSI and embryos. Thus, the traceability of all reproductive samples (oocytes destined for IVF and sperm) is not yet ensured. WIDER IMPLICATIONS OF THE FINDINGS: The direct embryo tagging system developed here provides fertility clinics with a novel tool to reduce the risk of mix-ups in human ARTs. The system can also be useful in research studies that require the individual identification of oocytes or embryos and their individual tracking. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Sociedad Espanola de Fertilidad, the Spanish Ministry of Education and Science (TEC2011-29140-C03) and the Generalitat de Catalunya (2009SGR-00282 and 2009SGR 00158). The authors do not have any competing interests. PMID- 24227080 TI - Design and development of a fiber-optic immunosensor utilizing near-infrared fluorophores. AB - The design and application of a fluorescent fiber-optic immunosensor (FFOI) are reported. The FFOI is utilized for the detection of antibody/antigen binding within the near-infrared (NIR) spectral region. The technique is developed through the combined use of fiber-optic, semiconductor laser-excitation, fluorescence detection, NIR dye, and immunochemical techniques. The antibody is immobilized on the FFOI and utilized as a recognition component for trace amounts of specific antigen. The FFOI is constructed to utilize an antibody sandwich technique. The assay involves the immobilization of the capture antibody on the sensing tip of the FFOI followed by the exposure of the immobilized sensing tip to the antigen. The antigen-coated FFOI is then introduced to a second antibody previously labeled with the NIR dye. Typical measurements are performed in about 15 min. A semiconductor laser provides the excitation (780 nm) of the immune complex. The resulting emission is detected by a silicon photodiode detector (820 nm). The intensity of the resulting fluorescence is directly proportional to the concentration of the antigen. The sensitivity of the analysis reaches 10 ng/ml and the response time is 10-15 min. PMID- 24227081 TI - Assessment of murine neuroblastoma (N1E-115) resting membrane potential by confocal microscopy. AB - Digital imaging (confocal microscopy) and a slow potentiometric dye (tetramethylrhodamine methyl ester) were used to assess the resting membrane potential (V m) of murine neuroblastoma cells (N1E-115). The averageV m was found to be -64.0+/-2.0 mV. The difference between this and the previously reported higher values was attributed to the use of glass microelectrode techniques that probably caused mechanical injury to the cell membranes: Digital imaging of N1E 115V m was found to be sensitive, reproducible, fast, and simple. PMID- 24227082 TI - Fluorescence lifetime characterization of magnesium probes: Improvement of Mg(2+) dynamic range and sensitivity using phase-modulation fluorometry. AB - We measured the Mg(2+)-dependent absorption spectra, emission spectra, quantum yields, and intensity decays of most presently available fluorescent magnesium probes. The lifetimes were found to be strongly Mg(2+) dependent for Mag-quin-1, Mag-quin-2, magnesium green, and magnesium orange and increased 2- to 10-fold upon binding of Mg(2+). The lifetimes of Mag-fura-2, Mag-fura-5, Mag-fura red, and Mag-indo-1 were similar in the presence and absence of Mg(2+). Detailed timeresolved measurements were carried out for Mag-quin-2 and magnesium green using phase-modulation fluorometry. Apparent dissociation constants (K d) were determined from the steady-state and time-resolved data. Their values were compared and discussed. Mg(2+) sensing is described using phase and modulation data measured at a single modulation frequency. Phase angle and modulation data showed the possibility of obtaining a wider Mg(2+)-sensitive range than available from intensity measurements. A significant expansion in the Mg(2+)-sensitive range was found for Mag-quin-2 using excitation wavelengths from 343 to 375 nm, where the apparentK d from the phase angle was found to vary from 0.3 to about 100 mM. Discrimination against Ca(2+) was also measured for Mag-quin-2 and magnesium green. Significant phototransformation and/or photode-composition, which affect the sensitivity to Mg(2+), were observed for Mag-quin-2 and magnesium green under intense and long illumination. PMID- 24227083 TI - Photometric and fluorimetric study of the acid-base behavior of 2,2'-diquinolyl and 2,2',2"-terpyridyl. AB - A photometric and fluorimetric study of the acid-base behavior of 2,2'-diquinolyl and 2,2',2"-terpyridyl was performed. In sulfuric acid medium, the doubly charged 2,2'-diquinolynium ion undergoes the first dissociation atH 0=0.20+/-0.09, as determined by fluorimetry (lambdaex=336 nm, lambdaem=424 nm). Photometric titration is less accurate because of the overlapping of the absorption spectra. The second dissociation constant of 2,2'-diquinolyl was determined by fluorimetric titration (lambdaex=336 nm, lambdaem=420 nm), obtaining a value of 3.67+/-0.03. The triply charged 2,2',2"-terpyridyl molecule was found to undergo the first dissociation atH 0=-7.17+/-0.04, as determined by fluorimetric titration (lambdaex=316 nm, lambdaem=350 nm), in aqueous sulfuric acid medium. Photometric titration (lambda=335 nm) was performed in the presence of 6.5% ethanol because of the low solubility of the compound in water. In this ethanolic?water medium, a value of the dissociation constant atH 0=-7.39+/-0.03 was calculated. The second dissociation constant was determined to be 2.81+/-0.12 by photometric titration at 285 nm, and values of 4.03+/-0.26 and 4.16+/-0.20 were found for the third dissociation constant by photometric titrations at 320 and 295 nm, in 10% ethanol, in close agreement with previously reported values. The fluorimetric titration profile obtained by exciting at 274 nm and measuring the fluorescence emission at 350 nm, in the zone betweenH 0=-3 and pH=10, is complicated by the several equilibria involved. PMID- 24227084 TI - Filter switching device for dual-wavelength videoimaging. AB - An inexpensive, dual-wavelength, videoimaging system that can be used for parallel observation of two fluorescent dyes is described. All four filters, two for excitation and two for emission, are placed on the same oscillating holder. Filters are coupled with a single dichroic mirror having two spectral windows. A coil driven by an electronic circuit connected to photosensors, which determine the position of the holder, moves the magnet that shifts the position of the filters. Since the filter holder is placed between two springs, it oscillates with the frequency of mechanical resonance. As a result the filter switching did not require much power and did not produce significant vibrations of the base. Switching frequencies up to 4.5 s(-1) were reached with the first experimental device. System performance was tested using phospholipid vesicles loaded with water-soluble and membrane dyes. It has been demonstrated that the device can be used successfully in experiments on membrane fusion with rhodamine- and calcein labeled liposomes. PMID- 24227086 TI - Development of a laser-based fluorescence microscope with subnanosecond time resolution. AB - This report describes the development of a fluorescence microscope based on a standard inverted optical microscope which incorporates a pulsed picosecond dye laser excitation source and a detector consisting of a gated image intensifier coupled to a CCD camera. Fluorescence images have been obtained using gate durations of 0.5 ns from this apparatus, representing a reduction in gate duration of an order of magnitude compared with similar instruments reported by others recently. Subnanosecond gated fluorescence images of V79-4 Chinese hamster lung fibroblasts stained with a phthalocyanine photosensitizer used in photodynamic therapy are presented. The results of these measurements are discussed in terms of the intracellular distribution of the sensitizer. Other potential applications and limitations of this technique are also outlined. PMID- 24227085 TI - Diffusion-enhanced resonance energy transfer shows that linker-DNA accessibility decreases during salt-induced chromatin condensation. AB - Accessibility of linker-DNA chromatin during salt-induced condensation of chicken erythrocytes chromatin was studied by diffusion-enhanced resonance energy transfer. A terbium complex was covalently bound to linker-DNA and fluorescein molecules bound to latex particles with diameters ranging from 14 to 2470 nm were used as acceptor. The accessibility of linker-DNA to molecules with a diameter superior to 14 nm diminished during condensation, but for an acceptor diameter of 14 nm or less, no accessibility variation was observed. It can be concluded that (1) linker-DNA is located inside the fiber when chromatin is in the condensed state, (2) chromatin condensation can prevent the approach to DNA due to steric hindrance, (3) salt-induced chromatin condensation is a gradual process, and (4) condensed chromatin models containing a central cavity are more likely. PMID- 24227087 TI - An expert system for water quality modelling. AB - The RAISON-micro (Regional Analysis by Intelligent System ON a micro-computer) expert system is being used to predict the effects of mine effluents on receiving waters in Ontario. The potential of this system to assist regulatory agencies and mining industries to define more acceptable effluent limits was shown in an initial study. This system has been further developed so that the expert system helps the model user choose the most appropriate model for a particular application from a hierarchy of models. The system currently contains seven models which range from steady state to time dependent models, for both conservative and nonconservative substances in rivers and lakes. The menu driven expert system prompts the model user for information such as the nature of the receiving water system, the type of effluent being considered, and the range of background data available for use as input to the models. The system can also be used to determine the nature of the environmental conditions at the site which are not available in the textual information database, such as the components of river flow. Applications of the water quality expert system are presented for representative mine sites in the Timmins area of Ontario. PMID- 24227088 TI - Expres: An expert system for assessing the fate of pesticides in the subsurface. AB - The expert system described here is designed to aid regulatory personnel in their assessment of the potential for pesticides to contaminate the soil and groundwater environment. The expert system, known as EXPRES (EXpert system for Pesticide Regulatory Evaluation Simulations), consists of existing numerical models which are used to simulate the transport and transformation of pesticides in the unsaturated zone, coupled with a knowledge-based system that guides the user through the choice of all the necessary information for characterizing the physical, meteorological, hydrogeological, pedological and agricultural settings of typical agricultural regions across Canada, as required by the pesticide model. The expert system is designed to be used as a management tool to aid in policy decisions. Thus, its purpose is to provide an assessment of the potential hazards and to identify if further study is warranted. PMID- 24227089 TI - Derivation of unit and flood hydrographs using a gis. AB - A geographic information system (GIS) supporting a flood hydrograph prediction software package is described. The hydrograph prediction method is based on the convolution of excess rainfall with a synthetic unit hydrograph, derived by the Soil Conservation Service runoff curve number and a regional dimensionless unit hydrograph method, respectively. The GIS uses a raster method to store the following data: land use and land cover, soil type, rainfall intensity-frequency duration statistics, runoff curve numbers (CN), regional dimensionless unit hydrograph, and regional lag-time relationship. The GIS has also the capability of computing a number of watershed and hydrologic parameters required for predictions, such as a watershed average rainfall and CN value, area, centroid, stream length etc. Most of the data for such computations are input from a digitizer. Substantial time and cost savings are possible once the data base has been created. Application of the system is illustrated by an example predicting flood frequency curves for selected watersheds in Alberta's Rocky Mountain foothills, Canada. PMID- 24227090 TI - An expert system for assessing safety and security of heterogeneous public water sources. AB - We have implemented a diagnostic system designed to advise on the likely causes of sanitary problems with public water sources. The approach to the problem makes extensive use of rule based expert systems and multi media information (maps, data, text, expert knowledge). The rules were based on actual water survey data, with a weighting scheme designed to highlight causes of health risks approximately in reverse order of importance (where such order may be presumed to exist). Out put is a vailable in one of several languages. PMID- 24227091 TI - Evaluation of the effects of acid precipitation in eastern Canada using the raison system. AB - Evaluations have been made of the key chemical factors in the aquatic effects upon surface waters due to acidic precipitation in eastern Canada. The region of Canada east of the Manitoba/Ontario border was divided into 22 aggregates and assessments of inorganic and organic ion chemistry appraised relative to sulphate deposition rates and distributions. Aquatic sensitivity is largely dominated by the concentration, distribution and magnitude of SO inf4 (sup2-) (sulphate) deposition and by the prevalent geology and derived soils found in each aggregate. The RAISON system provided an adaptable and highly flexible platform to evaluate interactively, multiple data sets of divergent characteristics. Attributes usually associated with geographical information systems are significantly augmented by quantitative numerical and stochastic capabilities that were used extensively in this study. PMID- 24227092 TI - A knowledge-based approach to regional acidification modelling. AB - Data from over 2000 stations and knowledge from experts on atmospheric transport, soil geochemistry, lake chemistry, wetland processes and acidification modelling were assembled in an expert system. The data were grouped by aggregates of tertiary watersheds based on water chemistry knowledge. A set of expert rules was used to determine which of six existing models was most appropriate for a given set of data. Comparison of computed and observed alkalinity indicated median relative errors from 11.3-17.9%, with regression slopes ranging from 0.91-1.18 and regression coefficients between 0.82 and 0.99. The expert model performance was further confirmed with paleolimnological data and other independent sets of data. The sensitivity of the predicted alkalinity was illustrated by changing some of the rules. Given that the rules were acceptable by experts and produced reasonable agreement with observations, the knowledge-based system seemed a viable approach to the impact assessment of acidic deposition. PMID- 24227093 TI - The predicted effect of SO2 emission controls on the water quality of eastern Canadian lakes. AB - Changes in SO inf4 (sup2-) deposition predicted to occur in response to implementation of announced SO2 emission control programs in Canada and the U.S.A. have been used as input to water chemistry models thereby giving an estimate of the changes in lake acid neutralizing capacity (ANC) and pH that can be expected from these programs. Eastern Canada has been divided into 22 subregions for the purpose of this analysis. Relative to the current level (1982 86) of SO inf4 (sup2-) deposition (Scenario 1), the effect of the Canadian SO2 emission control program alone (Scenario 2) is compared to that obtained when controls are implemented throughout North America (Scenarios 3 and 4). SO2 emission reduction will effect a shrinkage of the high wet SO inf4 (sup2-) deposition field in NE North America such that under Scenario 4 conditions, almost no area will remain in Canada that receives >20 kg ha(-1) yr(-1). The greatest decrease in deposition and resulting change in lake chemistry occurs in southern Ontario and southwestern Quebec. ANC distributions shift to higher concentrations and the percentage of lakes having pH<6 decreases in these areas. The Atlantic Provinces will obtain only a minor benefit from the control programs, i.e. experiencing only a small decrease in deposition and improvement in water quality. High sensitivity of the terrain in many parts of Atlantic Canada means that large numbers of lakes will remain acidic (i.e. ANC<0) and/or have pH<6 (an important biological threshold) even after full implementation of the current plans for SO2 control in Canada and the U.S. PMID- 24227094 TI - A prototype expert system for fishway design. AB - The design of structures for fish passage in rivers and streams provides an opportunity to apply expert system concepts to a design problem. Fishways contribute to the sustainable development of water resources projects by providing a path that allows fish migrations to be maintained. A prototype expert system (FDES) has been developed to recommend the most suitable fishway type for given design conditions. A recommendation is provided on the basis of fishway hydraulics, fish passage performance, and cost requirements. Fishway design demands expertise in various scientific disciplines such as hydrology, hydraulics, and fish biology. Expert system technology may be used to reduce design time requirements and to serve as a teaching aid to inexperienced engineers by organizing and accessing the cumulative knowledge of the most experienced designers. The rule-based expert system development tool, VP-Expert, supplies the backward chaining control structure for accessing the knowledge within the prototype. PMID- 24227095 TI - A physically based method for prediction of runoff frequencies. AB - A method is described for predicting changes in flood frequencies resulting from various causes affecting runoff in a watershed. The method utilizes the curve number and the traingular unit hydrograph procedures of the United States Department of Agriculture's Soil Conservation Service to transform rainfall frequencies into frequencies of peak discharge. The theory underlying the method is discussed. Application is illustrated by an example. PMID- 24227096 TI - Plotting formula for pearson type III distribution considering historical information. AB - Most of the existing plotting position formulas have been proposed for use in the analysis of systematic flood records, but little has been reported on the plotting formulas for historical or non-systematic flood samples. In particular, no previous investigations have specifically examined the probability plots for the Pearson type III (P3) distribution in the analysis of historical flood information. The present paper suggests a new plotting position formula for the P3 distribution for use with both systematic and historical flood records. The proposed formula has a simple structure as do most existing formulas, but it is more flexible because in can take explicitly into account the skewness coefficient of the underlying distribution. Further, results of graphical and numerical comparisons have demonstrated that the suggested formula provided the least bias in flood quantile estimation as compared with many available plotting formulas, including the well-known Weibull formula. Finally, results of a numerical example using actual flood data have indicated the practica convenience of the proposed plotting formula. It can be concluded that the formula developed in this study is the most appropriate for the P3 distribution in the analysis of flood records considering historical information. PMID- 24227097 TI - Application of generalized linear models to the analysis of toxicity test data. AB - Generalized linear models give a unified approach to the performance of regression analysis of dichotomous, count or continuous data. This paper studies binomial, negative binomial and gamma regression models and gives a detailed description of inference procedures based on them. In particular, the maximum likelihood procedure is described for a logistic function (binomial regression) or a log-linear regression model (negative binomial and gamma regression). The process of model fitting and evaluation is illustrated by examples referring to the determination of endpoints in acute and chronic toxicity tests. PMID- 24227098 TI - Statistical analyses of regional surface water quality in southeastern Ontario. AB - Historical records from Ontario's Provincial Water Quality Monitoring Network (PWQMN) for rivers and streams were analyzed to assess the feasibility of mapping regional water quality patterns in southeastern Ontario which spans two major geologic zones, the Precambrian Shield and the St. Lawrence Lowlands, thus serving as a paradigm for much of Ontario. Despite biases toward the populated Lowlands and associated pollution problems, general spatial trends are evident via the analysis of intervariable relations, individual parameter maps and multivariate analysis. Using a robust algorithm designed to identify outliers and abstract underlying bivariate relations, a linear regional hardness-alkalinity relation was derived, where most anomalies proved to be mine drainage impacted sites. Regionally, multivariate ordination reveals that central tendencies of common indicators of ionic strength and nutrient richness correlate positively and that site clusters broadly reflect the transition from oligotrophic Shield waters to eutrophic conditions of heavily agricultural Lowland streams. Results suggest that on the Shield more precisely delineated aquatic regions may be realized by applying GIS to integrate river and synoptic lake survey data. Further synthesis with bedrock and surficial geology, physiography, pedology and other temporally invariant spatial attributes should yield regional patterns of background quality from which locally 'attainable' water objectives might be defined. Additional synoptic surveys of sedimentary Lowland streams may be required as most available sites relflect anthropogenic pollution. PMID- 24227099 TI - Monitoring statistics which have increased power over a reduced time range. AB - The problem of monitoring trends for changes at unknown times is considered. Statistics which permit one to focus high power on a segment of the monitored period are studied. Numerical procedures are developed to compute the null distribution of these statistics. PMID- 24227100 TI - Trend evaluation of water quality parameters in the Niagara and St. Lawrence Rivers. AB - Physical and chemical (nutrients and major ions) indicators of water quality monitored by Environment Canada between 1977 and 1987 in the Niagara River at Niagara-on-the-Lake and in the St. Lawrence River at Wolfe Island are analyzed for seasonal and annual variations. Parametric methods such as moving averages and linear regression and nonparametric methods (Spearman's rank coefficient) are used to test for the existence of trends in these data. The results indicate that specific conductivity, sodium and chloride have decreased significantly over the period of study. During the same period there is no significant trend for either discharge and nutrients. PMID- 24227101 TI - Detection of water quality changes along a river system. AB - Water quality monitoring networks are generally multi-purpose, and thus the data generated are expected to provide information on a set of objectives. Two questions that are fundamental to these objectives are the detection of long term trends and of differences between locations. The extent to which these questions can be answered and the types of statistical methods which can be used are considered in a case study of conventional parameters sampled monthly for nine years. Regression and nonparametric methods, which explicitly account for seasonality, are compared for both the determination of change over time and of differences between locations. Changes over time in the form of step changes and differences between locations which depend upon season were found. PMID- 24227102 TI - Variances and covariances underlying loading estimates and part-whole relationships. AB - The effluent limit guidelines are usually based on loading estimates of chemicals discharged into the environment. The loading estimates, calculated as the product of flow times concentration, have underlying mathematical relationships in terms of variances and covariances. These relationships are presented by using the moment generating function technique. Estimators of loading means are compared. Cramer-Rao bounds for the variances of unbiased estimators of the loading means are presented. Mathematical details underlying several part-whole and ratio estimators are also presented. An understanding of these relationships should provide unbiased estimates of loading means, variances and covariances. PMID- 24227103 TI - Design and model based inferences with applications to acidification of lakes in eastern Canada. AB - The design and model based approaches for making inferences about the number of lakes affected by acidic deposition and the chemical characteristics of aquatic resources at risk are described. In many instances when the lakes in the sample are selected for convenience without any randomization, the model based approach continues to provide valid inferences about the population of lakes. The performances of the two approaches are compared using a small population of 177 lakes which are located in southern Quebec. Examples from the Canadian acid rain monitoring program in the Atlantic provinces are also given. PMID- 24227104 TI - Editorial. PMID- 24227105 TI - Patients' perceptions of the potential of breathing training for asthma: a qualitative study. AB - BACKGROUND: Poor symptom control is common in asthma. Breathing training exercises may be an effective adjunct to medication; it is therefore important to understand facilitators and barriers to uptake of breathing training exercises. AIMS: To gain insight into patients' perceptions of breathing training exercises designed to help control asthma symptoms. METHODS: Semi-structured think-aloud interviews were conducted with 29 people with asthma about their views of a booklet on breathing training exercises. RESULTS: Thematic analysis showed breathing training exercises were seen as acceptable in principle because they were viewed as nonpharmacological, holistic, unobtrusive, and likely to increase patient confidence in managing symptoms. Anticipated disadvantages included the time required and perceived irrelevance for those with well-controlled asthma. These views were influenced by prior experience of changing breathing, wanting to self-manage asthma, negative views of medication, and perceived asthma control/severity. Anticipated barriers to carrying out the exercises included difficulties with nose breathing, remembering to do them, and persevering with them. Anticipated facilitators included monitoring tools and social support. CONCLUSIONS: The idea of breathing training was viewed positively as an acceptable non-pharmacological treatment that patients can do discreetly to help them breathe more easily and reduce their reliance on medication. Uptake of breathing training may be greater among those who perceive their asthma as severe and/or have negative views of medication. To enhance uptake, it might be helpful to present breathing training exercises as holistic skills that can also benefit those with mild symptoms. PMID- 24227106 TI - Electroantennogram responses ofHyles lineata (Sphingidae: Lepidoptera) to volatile compounds fromClarkia breweri (Onagraceae) and other moth-pollinated flowers. AB - Electroantennograms (EAGs) from field-collectedHyles lineata moths were recorded in response to 10 individual floral volatiles identified fromClarkia breweri (Onagraceae), to 22 scent compounds produced by other moth-pollinated flowers and to eight ubiquitous "green leaf volatiles." Females' EAGs were generally 1.5- to 2-fold greater than those observed for male moths. Female:male EAG rank orders were significantly correlated, but marked differences in order were observed for some compounds (e.g., benzyl alcohol, cinnamic aldehyde, geraniol, and linalool). Linalool, benzyl acetate, methyl salicylate, and pyranoid linalool oxide elicited the largest EAG responses (-1.2 to -0.8 mV) among scent compounds fromC. breweri. EAG responses were significantly lower for monoterpenes as a pooled compound class than for aromatic esters, alcohols and aldehydes, fatty acid derivatives, N bearing compounds and oxygenated terpenoids. EAG responses to structurally related scent compounds were not significantly different in most cases. Both male and femaleH. lineata were sensitive to mostC. breweri scent compounds at 10(-2) to 10(-4) ug/ul doses, and rank order in potency varied with the dose/concentration tested.H. lineata's olfactory sensitivity to diverse volatile compounds across a range of doses/concentrations suggests that a broad array of volatiles could function as floral attractants for foraging hawkmoths. PMID- 24227107 TI - Exogenous jasmonates simulate insect wounding in tomato plants (Lycopersicon esculentum) in the laboratory and field. AB - Wounding increases the levels and activities of several defense-related proteins in the foliage of the tomato plant,Lycopersicon esculentum Mill. Evidence indicates that two of these responses, the systemic increases in polyphenol oxidase and proteinase inhibitors, are regulated by an octadecanoid-based signalling pathway which includes the wound hormone, jasmonic acid. It is not known whether other responses to wounding are also regulated by this same signalling pathway. In this paper, we show that application of jasmonates (jasmonic acid or its volatile derivative, methyl jasmonate) in low concentrations to foliage of young tomato plants induced, in a dose-dependent manner, the same protein responses-polyphenol oxidase, proteinase inhibitors, lipoxygenase, and peroxidase-as doesHelicoverpa zea Boddie feeding. Application of jasmonic acid to a single leaflet of four-leaf tomato plants induced these four proteins in a spatial pattern nearly identical to that produced by localized feeding ofH. zea. Exogenous jasmonic acid also decreased suitability of foliage for the beet armyworm,Spodoptera exigua Hubner in the laboratory. Based on these results, we conducted an experiment to measure the effects of jasmonic acid spray under field conditions. We provide the first evidence that jasmonic acid spray on field plants induces production of chemical defenses above the levels found in unsprayed controls. Exogenous jasmonic acid sprayed on plants in agricultural plots increased levels of polyphenol oxidase and proteinase inhibitors. Because application of jasmonic acid induces these defensive compounds at low concentrations in a manner similar to natural wounding, it may prove to be a useful tool for stimulating plant resistance to insects in the field. PMID- 24227108 TI - High recaptures and long sampling range of pheromone traps for fall web worm mothHyphantria cunea (Lepidoptera: Arctiidae) males. AB - Newly emerged males ofHyphantria cunea (Drury) (Lepidoptera: Arctiidae), marked with different fluorescent colors, were recaptured by pheromone trapping. Three Uni-traps, baited with (3Z,6Z)9,10-epoxyheneicosadiene, (9Z,12Z,15Z)octadecatrienal, and (3Z,6Z)9,10-epoxyheneicosa-triene in a 1:10:1 ratio, total 6 mg/dispenser, were placed in a line 15 m apart, perpendicular to the dominant wind direction, and checked after 12, 36, and 60 hr. At dusk, releases of 10-25 males were made over distances from 30 to 250 m, during 4 periods over a soybean field (nonhost plant). Recapture rates were high; of a total of 176 males released, 115 were recaptured with 88% of these within 12 hours. Between 40 and 100% of males were recovered over shorter distances (30-150 m), and between 10-24% at longer distances (200 and 250 m). No other species or unmarked males were captured. The trapping period showed little effect on recaptures. The central trap of the three traps had somewhat higher catches, but the slope of the regression of recapture over distance did not differ among traps. There was a significant decline of recapture over distance (r=-0.56) for catches of individual traps but a large scatter. Summed recaptures per distance gave less scatter and hadr=-0.86, allowing calculation of the maximum sampling range (R s ) after 60 hr as 340 m with a 95% confidence interval of 190-710 m (regression of arcsin ?p and ?R). The area of sampling, found by integrating the probability function of recapture over distance, from the source to maximumR, was 7 ha. The high recapture rates and the longR,. compared to those in the literature for other taxa, indicate that pheromone traps are highly efficient sampling devices in this species. PMID- 24227109 TI - Role of allelopathy as a possible factor associated with the rising dominance ofBunias orientalis L. (Brassicaceae) in some native plant assemblages. AB - Leaf extracts ofBunias orientalis were shown to inhibit seed germination of a variety of cultivar plant species and of species cooccurring withB. orientalis in the field. Root exudate solutions and leaf litter leachates ofB. orientalis were tested for their allelopathic activity using seedling growth assays. Additionally, in comparative seedling growth assays soil cores removed from denseB. orientalis stands were tested bimonthly for elevated allelopathic effects. The impact of root exudates on seedling growth was generally weak and varied between species. Similar results were obtained for the effect ofB. orientalis leaf litter leachates on seedlings grown in sand culture relative to the effect of leaf litter leachates of a plant species mixture. When soil as a growth substrate was used, no consistent differences in seedling growth were obtained between the two litter leachate treatments. In the soil core experiment seedlings grown in soil cores collected from a denseB. orientalis stand unexpectedly showed better performance than seedlings grown in soil cores collected from a nearby mixed plant stand withoutB. orientalis, at least in early spring and late autumn. Predominating nutrient effects are, therefore, assumed to conceal a potentially increased allelopathic effect of soil beneath denseB. orientalis stands. It is concluded that other factors than allelopathy must be investigated to explain the rapid establishment of dense stands of this alien plant species. PMID- 24227110 TI - Intercaste, intercolony, and temporal variation in cuticular hydrocarbons ofCopotermes formosanus shiraki (Isoptera: Rhinotermitidae). AB - We characterized the variation in cuticular hydrocarbon mixtures between seven colonies of the Formosan subterranean termite,Coptotermes formosanus Shiraki, from the same population. We report differences between castes, between colonies, and within the population over time to assess seasonality. Colonies ofC. formosanus from Oahu, Hawaii, were sampled for 25 months. Each month, one sample each of 200 workers, 50 soldiers, nymphs, or alates from each colony was subjected to gas chromatography-mass spectrometry (GC-MS) analysis of the cuticular hydrocarbons. We resolved 39 individual peaks and identified 52 individual or isomeric mixtures of hydrocarbons. Onlyn-alkanes and methyl branched alkanes occur; no olefins were found. Internally branched monomethylalkanes were the most abundant class of hydrocarbons, representing 45% to 50% of the total 9-;11-;13-Methyl-heptacosane accounted for over 30% of the total hydrocarbon for all castes. 2-Methyl- and 3-methylalkanes comprise approximately 30% of the total. Internally branched dimethylalkanes constitute 15% to 20% of the total cuticular hydrocarbon. Only one trimethylalkane, 13,15,17 trimethylnonacosane, was found in small amounts. The hydrocarbon mixtures of all four castes were similar. Quantitative differences in hydrocarbon mixtures among the castes were easily displayed using canonical discriminant analysis. Soldiers and workers are significantly different from one another and from nymphs and alates. Nineteen peaks are statistically significant between workers and soldiers. Nymphs and alates were not statistically different. We detected statistically significant quantitative differences between colonies in 18 peaks for workers and 12 peaks for soldiers. Each of the colonies ofC. formosanus can be separated from the others by the proportions of their hydrocarbon components. We detected statistically significant differences between months of the year for 12 peaks for workers and four peaks for soldiers; two peaks each for workers and soldiers showed distinct, seasonal trends. This seasonal shift in proportions of hydrocarbons correlates with the production of alates. PMID- 24227111 TI - Aggregation pheromones ofDrosophila immigrans, D. phalerata, andD. subobscura. AB - Aggregation pheromones ofDrosophila immigrans, D. phalerata andD. subobscura were demonstrated by testing attraction of adult flies to hexane extracts of the flies in a windtunnel bioassay. Extracts of adult males of all species attracted conspecific males and females. However,D. subobscura flies were attracted only when the extract (cVA) in the extracts of adult maleD. immigrans andD. phalerata. Both species were attracted to synthetic cVA. Male and femaleD. phalerata. Both species were attracted to synthetic cVA. Male and femaleD. subobscura produced 5,9-pentacosadiene, 5-pentacosene, 2-methylhexacosene and 5,9-heptacosadiene, while only maleD. subobscura produced (Z)-5-tricosene and minor amounts of cVA. PMID- 24227112 TI - Experiments on bioassay sensitivity in the study of allelopathy. AB - The purpose of these experiments was to study the effects of various experimental procedures and conditions on bioassay sensitivity in allelopathic studies. The following factors were considered: bioassay methods, choice of test species, the effect of osmotic potential on germination and growth of the test species, growth in dark or in light and the effect of concentrating the extracts in vacuo. Extracts from rape and rye were used in the studies to act as allelopathic agents. Ryegrass appeared as the most sensitive test species when grown horizontally on quartz sand, while radish was the most sensitive test species when grown on filter paper in transparent boxes at a 45 degrees angle. Root length was the most sensitive growth variable measured. Percent germination appeared a more sensitive measure than the speed of germination index, "S", when germinated seeds were counted after one and two days for radish and ryegrass, respectively. A rise in the osmotic potential affected germination more than root length, and radish appeared more sensitive to a rise in osmotic potential than ryegrass. A confounding of germination and root length inhibition may therefore, give misleading results. PMID- 24227113 TI - Green leaf volatiles as antiaggregants for the mountain pine beetle,Dendroctonus ponderosae Hopkins (Coleoptera: Scolytidae). AB - We tested the hypothesis that green leaf volatiles act as antiaggregants for the mountain pine beetle (MPB),Dendroctonus ponderosac Hopkins. In coupled gas chromatographic-electroantennographic detection (GC-EAD) analysis MPB antennae responded to 30 ng doses of all six-carbon green leaf alcohols tested [1-hexanol, (E)-2-hexen-1-ol, (Z)-2-hexen-1-ol, (E)-3-hexen-1-ol, and (Z)-3-hexen-1-ol], but not to the aldehydes, hexanal or (E)-2-hexenal, or to alcohol or aldehyde homologues with more or fewer than six carbon atoms. In field trapping experiments a blend of green leaf alcohols [1-hexanol, (Z)-2-hexen-1-ol, (E)-3 hexen-1-ol and (Z)-3-hexen-1-ol] effectively disrupted the response to attractive semiochemicals; a blend of the aldehydes hexanal and (E)-2-hexenal was inactive. The two best disruptants. (E)-2-hexen-1-ol and (Z)-3-hexen-1-ol, reduced catches of both sexes to levels not significantly different from catches in unbaited control traps. They also reduced the attack on trees baited with attractive MBP pheromones to a level not significantly different from that on unbaited control trees. Neither of the clerid predators captured,Enoclerus sphegeus (F.) norThanasimus undatulus (Say), was repelled by green leaf volatiles. Our results suggest that green leaf alcohols are promising disruptants which may be used to supplement the antiaggregation pheromone, verbenone, in protecting single high value trees as well as carefully selected stands with low-level populations of MPBs. PMID- 24227114 TI - Phlorotannin-protein interactions. AB - Tannins are one of the most broadly distributed types of plant secondary compounds, and have been the focal point for many studies of plant/herbivore interactions. Tannins interact strongly with proteins, so that the fate and effects of ingested tannins are in part dependent on the mode of interaction of the tannin with dietary and endogenous proteins in an herbivore's gut. We investigated the factors affecting the precipitation of proteins by phlorotannins from three species of marine brown algae:Carpophyllum maschalocarpum, Ecklonia radiata, andLobophora variegata. Phlorotannins were precipitated by proteins in a pH-dependent and concentration-dependent fashion. Precipitation also varied as a function of the presence of reducing agent, the type of phlorotannin or protein used, and the presence of organic solvents such as hydrogen bond inhibitors. Of particular significance was the ability of some phlorotannins to oxidize and form covalent bonds with some proteins. In contrast, under similar experimental conditions three types of terrestrial tannins (procyanidins, profisetinidins, and gallotannins) apparently did not form covalent complexes with proteins. Our results suggest several ways in which the biological activity of phlorotannins may vary as a function of the properties of the gut environment of marine herbivores. Moreover, we identify specific structural characteristics of phlorotannins which affect their tendency to oxidize, and thus, their potential effects on marine herbivores. PMID- 24227115 TI - Reassessment of the roles of the peritrophic envelope and hydrolysis in protecting polyphagous grasshoppers from ingested hydrolyzable tannins. AB - We examined several of the mechanisms that have been reported to enable polyphagous grasshoppers (Orthoptera: Acrididae) to tolerate ingested hydrolyzable tannins: hydrolysis, adsorption on the peritrophic envelope, and peritrophic envelope impermeability. None of these mechanisms explain the tolerance ofMelanoplus sanguinipes to ingested tannic acid. In this species, tannin hydrolysis was 12-47% complete, adsorption accounted for less than 1% of the tannic acid contained in the midgut, and the peritrophic envelope was permeated by several gallotannins. The foregut is the main site for the chemical transformation of tannic acid in this species. InPhoetaliotes nebrascensis, hydrolysis was more extensive (82% complete), but the peritrophic envelope was readily permeated by two gallotannins. Oxidizing redox conditions were found in the guts of both species, and ingested tannins were oxidized inM. sanguinipes. We hypothesize that the tolerance of some polyphagous grasshoppers to ingested hydrolyzable tannins may be the consequence of their ability to tolerate the reactive oxygen species generated by polyphenol oxidation, whereas others may rely on rapid and extensive hydrolysis. PMID- 24227116 TI - Mediation of cardiac glycoside insensitivity in the monarch butterfly (Danaus plexippus): Role of an amino acid substitution in the ouabain binding site of Na(+),K (+)-ATPase. AB - The Monarch butterfly (Danaus plexippus) sequesters cardiac glycosides (CG) for its chemical defense against predators. Larvae and adults of this butterfly are insensitive towards dietary cardiac glycosides, whereas other Lepidoptera are sensitive and intoxicated by ouabain. Ouabain inhibits Na(+),K(+)-ATPase by binding to its alpha-subunit. We have amplified and cloned the DNA-sequence encoding the respective ouabain binding site. Instead of the amino acid asparagine at position 122 in ouabain-sensitive insects, the Monarch has a histidine in the putative ouabain binding site, which consists of 12 amino acids. Starting with the CG-sensitive Na(+),K(+)-ATPase gene fromDrosophila, we converted pos. 122 to a histidine residue as inDanaus plexippus by site-directed mutagenesis. Human embryonic kidney cells (HEK) (which are sensitive to ouabain) were transfected with the mutated Na(+),K(+)-ATPase gene in a pSVDF-expression vector and showed a transient expression of the mutatedDrosophila Na(+),K(+) ATPase. When treated with ouabain, the transfected cells tolerated ouabain at a concentration of 50 mM, whereas untransformed controls or controls transfected with the unmutatedDrosophila gene, showed a substantial mortality. This result implies that the asparagine to histidine exchange contributes to ouabain insensitivity in the Monarch. In two other CG-sequestering insects, e.g.,Danaus gilippus andSyntomeida epilais, the pattern of amino acid substitution differed, indicating that the Monarch has acquired this mutation independently during evolution. PMID- 24227117 TI - Isolation and identification of (3-methoxyphenyl)acetonitrile as a phytotoxin from meadowfoam (Limnanthes alba) seedmeal. AB - Ethyl ether, ethanol, and water extracts of meadowfoam (Limnanthes alba Hartweg ex. Benth.) seedmeal were prepared and bioassayed against velvetleaf (Abutilon theophrasti Medicus) and wheat (Triticum aestivum L. "Cardinal"). Both the ethyl ether and ethanol fractions, but not the water extract, inhibited velvetleaf and wheat radicle elongation. Fractionation of the extracts indicated that (3 methoxyphenyl)acetonitrile (3-MPAN) was the active compound from both extracts, comprising >97% of the active ethanol fraction. 3-Methoxybenzyl isothiocyanate, which had been previously shown to be the major breakdown product of glucolimnanthin, the majorL. alba glucosinolate, was not detected in either extract. Radicle elongation of velvetleaf and wheat were inhibited by 3-MPAN with I50 (the concentration required to inhibit growth by 50%) values of approximately 4 * 10(-4) M (velvetleaf) and 7*10(-4) M (wheat). PMID- 24227118 TI - The GDF5 SNP is associated with meniscus injury and function recovery in male Chinese soldiers. AB - Genetic factor have previously been shown to play an important role in sports injuries and recovery. GDF5 Single-Nucleotide Polymorphism rs143383 has been recently reported to be associated with fracture susceptibility. Furthermore, the effect of GDF5 during the recovery processes of trauma is increased. In the present study, we aimed to evaluate whether this SNP was associated with susceptibility to the meniscus injury and postoperative recovery in Chinese male soldiers. GDF5 SNP was genotyped in 135 male soldiers with meniscus injury and 400 healthy male controls. Moreover, the function recovery of the soldiers suffering from the meniscal repair was also assessed. Our data showed that the GDF5 TT genotype (60.0 vs. 47.25%; P=0.010) and T allele (76.3 vs. 68.75%; P=0.019) were significantly over-represented in the meniscus injury group compared with the control group. We found that the TC (P<0.05), CC (P<0.05) and C carriers (P<0.05) genotype exhibited significantly higher Lysholm Scores than the TT genotype at 1 month postoperative. In addition, the CC (P<0.05) genotype also demonstrated significantly higher Lysholm Scores than the TT genotype 2 months postoperative. Taken together, our results revealed that the GDF5 SNP was associated with susceptibility to the meniscus injury and postoperative function recovery in Chinese male soldiers. PMID- 24227119 TI - Exercise decreases susceptibility to homocysteine seizures: the role of oxidative stress. AB - The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity. PMID- 24227120 TI - Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects. AB - We investigated the early effects of whole body vibration (WBV) added to hypocaloric diet on insulin-resistance and other parameters associated with glucose regulation in sedentary obese individuals. We randomly assigned 34 patients to WBV plus hypocaloric diet (WBV group) or diet alone (CON group) for 8 weeks. Fasting and post-load glucose, insulin, lipids, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin were assessed. Insulin sensitivity index (ISI) was derived from oral-glucose-tolerance test. Body composition was evaluated with dual-energy X-ray absorptiometry. Both groups lost approximately 5% of weight, with greater reduction of body fat in WBV than in CON (-7.1+/-1.2 Kg vs. -5.3+/-1.0 Kg, p=0.003). Percent variation of ISI was more pronounced in WBV than in CON group (+35+/-4% vs. + 22+/-5%, p=0.002), accompanied by slight improvement in post-load glucose (-1.07+/-0.02 vs. - 0.12+/-0.01 mmol/l, p=0.031) but without changes in fasting levels. Adiponectin significantly increased in WBV group compared with CON (p=0.021 for comparison) whereas no differences in leptin and inflammatory markers were observed. In middle-aged sedentary obese subjects, WBV added to hypocaloric diet for 8 weeks improved body composition, insulin resistance, glucose regulation and adiponectin levels to a greater extent compared with diet alone. Efficacy and feasibility of this approach in the long term need to be ascertained. PMID- 24227121 TI - Validating the EMG(FT) from a single incremental cycling test. AB - The purposes of this study were to (1) identify the EMG(FT) from a single incremental cycle ergometry test and (2) validate this fatigue threshold by having participants perform constant workload rides at 70, 100 and 130% of the estimated EMG(FT). 11 healthy college-age participants performed incremental cycle ergometry on the initial visit. The EMG amplitude was recorded from the vastus lateralis muscle for each power output and fitted with linear regression which provided the estimated EMG(FT). In subsequent visits, participants exercised at 3 percentages of their EMG(FT) with the EMG amplitude recorded for each condition. The results indicated no significant (p>0.05) increases in EMG amplitude vs. time for the 70% and 100% workloads, respectively. In addition, the participants were able to maintain these exercise intensities for over 40 min. For the 130% workload, however, EMG amplitude vs. time increased significantly (p<0.001) and the participants were able to maintain the exercise condition for less than 12 min. These findings indicate that the EMG(FT) estimated from a single incremental cycle ergometry test is a valid measure of neuromuscular fatigue and may potentially be useful in assessing the efficacy of rehabilitative interventions. PMID- 24227122 TI - Comparison of selected lactate threshold parameters with maximal lactate steady state in cycling. AB - The aim of the present investigation was to compare power at "onset of blood lactate accumulation" (OBLA), "individual anaerobic threshold" (IAT) and "+1.5 mmol ? l(-1) lactate model" with power in maximal lactate steady state (MLSS) in cycling. However, there is a lack of studies concerning the absolute individual differences between different lactate parameters and MLSS.A total of 57 male participants performed several 30-min constant-load tests to determine MLSS by measuring blood lactate concentration (BLC). Depending on BLC, power was increased or decreased by 10 W in the following 30-min test. For detecting power at different threshold parameters, an incremental test was performed that began at 40 W and increased by 40 W every 4 min.Highly significant correlations were found between OBLA and MLSS: r=0.89 (mean difference -7.4 W); IAT and MLSS: r=0.83 (mean difference 12.4W), "+1.5 mmol ? l(-1) lactate model" and MLSS: r=0.88 (mean difference -37.4W). On average, the parameters of OBLA and IAT approximate MLSS with no significant differences. The "+1.5 mmol ? l(-1) lactate model" underestimates MLSS significantly.Based on Bland-and-Altman, the comparison of power of all threshold parameters with power in MLSS shows great individual differences despite the high regression coefficients and low mean differences between these methods. PMID- 24227126 TI - Differential filtration studies of carbon flux from living algae to microheterotrophs, microplankton size distribution and respiration in Lake Kinneret. AB - The flux of newly photosynthetically fixed, dissolved organic carbon (PDOC) from phototrophs to microheterotrophs in Lake Kinneret was examined by differential (3 and 0.4MUm) filtration after samples were incubated with(14)C-bicarbonate for 3 hours (in the light) and subsequently for 21 hours (in darkness). Only a small proportion (average about 10%) of the carbon fixed from(14)C-bicarbonate in the light was associated with particulate matter <3MUm. In 14 out of 16 experiments there was no significant decrease in the relative proportion of radioactivity associated with larger (>3MUm) organisms after the dark period, suggesting that the amount of PDOC taken up by unclumped, single bacteria (<3MUm) was not very great. Respiration rates, estimated by the decrease in(14)C particulate counts in the dark period, ranged from 3.4 to 21.2% of daylight net photosynthesis. In almost all cases, parallel experiments with additions of radioactive glucose or amino acids indicated that the majority of active heterotrophs passed through 3MUm filters. Apparent residence times for glucose and amino acids were 20 to 168 hours and 20 to 152 hours, respectively. PMID- 24227123 TI - Force-velocity profile: imbalance determination and effect on lower limb ballistic performance. AB - This study sought to lend experimental support to the theoretical influence of force-velocity (F-v) mechanical profile on jumping performance independently from the effect of maximal power output (P max ). 48 high-level athletes (soccer players, sprinters, rugby players) performed maximal squat jumps with additional loads from 0 to 100% of body mass. During each jump, mean force, velocity and power output were obtained using a simple computation method based on flight time, and then used to determine individual linear F-v relationships and P max values. Actual and optimal F-v profiles were computed for each subject to quantify mechanical F-v imbalance. A multiple regression analysis showed, with a high-adjustment quality (r2=0.931, P<0.001, SEE=0.015 m), significant contributions of P max , F-v imbalance and lower limb extension range (h PO ) to explain interindividual differences in jumping performance (P<0.001) with positive regression coefficients for P max and h PO and a negative one for F-v imbalance. This experimentally supports that ballistic performance depends, in addition to P max , on the F-v profile of lower limbs. This adds support to the actual existence of an individual optimal F-v profile that maximizes jumping performance, a F-v imbalance being associated to a lower performance. These results have potential strong applications in the field of strength and conditioning. PMID- 24227127 TI - Significance of algal extracellular products to bacteria in lakes and in cultures. AB - In simulated diurnal experiments withChlorella pyrenoidosa andPseudomonas fluorescens, bacterial growth was virtually confined to the daylight period and occurred at the expense of glycolate, the predominant extracellular product of the alga. Both glycolate levels and(14)C-DOC excretion rates were much lower in mixed algal-bacterial than in axenicChlorella cultures.This close coupling of bacterial growth to algal photosynthesis and extracellular release was also observed in Jack's Lake, but not in Lake Erie. Experimental enrichment with lake water particulates >30MUm suppressed the daytime growth of bacteria in Jack's Lake, but increased it dramatically in Lake Erie. Daylight doubling times for bacteria in lakewater ranged from 2 to 19 days. In mixed culture withChlorella, Pseudomonas had a doubling time of about 2 hours in the light. PMID- 24227128 TI - Respiratory studies on two small freshwater amoebae. AB - The changes in respiration rate and mean cell volume induced by temperature within the range 10 degrees C-25 degrees C were investigated in two small species of freshwater amoebae,Saccamoeba limax Page andVannella sp. Mean cell volume varied in response to temperature, with maxima at 20 degrees C inVannella sp. (10.15* 10(3) (+/-1.80)MUm(3) and 15 degrees C inS. limax (9.08*10(3) (+/ 0.93)MUm(3). Respiration rate increased over the temperature range investigated. The highest rates and the greatest rate of increase between temperatures occurred inVannella sp. Q10 ranged between 0.12 and 1.33 inS. limax and between 1.77 and 7.36 inVannella sp. A regression of log oxygen uptake versus log cell volume incorporating the data of the present investigation and the data of other workers on amoeba respiration is presented, and the ecological significance and application of such data discussed. PMID- 24227129 TI - Fluorescein diacetate hydrolysis as an estimator of microbial biomass on coniferous needle surfaces. AB - Estimating microbial standing crops and microbial production in natural habitats has been difficult for microbial ecologists. The present paper describes a simple spectrophotometric assay based on the hydrolysis of fluorescein diacetate which estimates well the standing crops of microbial cells on coniferous needles and twigs. A technique is also presented for correlating optical density readings with actual dry weights of microbial cells epiphytic on needles, and thus for standardizing the assay. The assay shows promise of broad applicability to other microbial habitats. PMID- 24227130 TI - Influence of zinc, lead, and cadmium pollutants on the microflora of hawthorn leaves. AB - Transect studies were conducted to determine the relative effects of zinc, lead, and cadmium pollution on microorganisms occurring on hawthorn leaves at varying distances from a smelting complex.Sporobolomyces roseus was absent from the most heavily contaminated leaves but, although lead was inhibitory, other environmental factors were also important in determining its overall population level. Conversely,Aureobasidium pullulans and nonpigmented yeasts showed a significant partial positive correlation with lead but were inhibited by zinc and/or cadmium. Numbers of bacterial colonies were only slightly reduced by the combined effect of all three metals, but total numbers of bacteria were highly negatively correlated with lead. Filamentous fungi, isolated by leaf washing, were only slightly inhibited by all three metals, and the degree of mycelial proliferation on senescent leaves was little affected by heavy metal pollution. Computer-generated maps were produced of the distribution ofA. pullulans in relation to zinc and lead fallout. PMID- 24227131 TI - Determination of volatile nematode exudates and their effects on a nematode trapping fungus. AB - Volatile compounds exuded from axenically grown free-living nematodes were determined with gas chromatographic and mass spectrometric techniques. Carbon dioxide evolved from 5-200 nematodes was determined with an ampoule technique, whereas total ammonia (NH3 + NH4 (+)) and acetic and propionic acids were determined by direct injection of water in which nematodes had been suspended for 1-3 days. CO2 amounted to about 80 ng nematode(-1) d(-1), total ammonia to 1-5 ng, and acetic and propionic acids to 0.5 and 1.0 pg nematode(-1) d(-1).The effects of these compounds on induction of trap formation in the nematodetrapping fungusArthrobotrys oligospora were tested. CO2 inhibited trap formation at 5-10% CO2 in air (v/v), whereas ammonia stimulated trap formation in a certain concentration range. No effects of acetic and propionic acids were noted for the concentrations tested. The combined effects of these volatiles in the aqueous environment are discussed on the basis of stoichiometric considerations. PMID- 24227132 TI - In vitro inhibition of root-rot pathogensPhellinus weirii, Armillariella mellea, Fomes annosus, andPhytophthora cinnamomi by a newly isolatedBacillus sp. AB - A Gram-positive bacterium that inhibits several root-rot pathogens was isolated from alder forest soil on the Oregon coast. This organism, similar toBacillus cereus, produces in culture media a heat-stable, broad-spectrum antibiotic which inhibits growth of four important Northwest conifer root disease fungi:Phellinus weirii (Murr.) Gilbertson,Fomes annosus (Fr.) Cke.,Armillariella mellea (Fr.) Karst., andPhytophthora cinnamomi Rands. PMID- 24227133 TI - Degradation of some phenoxy acid herbicides by mixed cultures of bacteria isolated from soil treated with 2-(2-methyl-4-chloro)phenoxypropionic acid. AB - Mixed bacterial cultures capable of using 2-methyl-4-chIorophenoxyacetic acid (MCPA) and 2, 4-dichlorophenoxyacetic acid (2, 4-D) as the sole source of carbon and energy were isolated from field soil treated with the herbicide (+/-)2-(2 methyl-4-chloro)phenoxypropionic acid (mecoprop). An enrichment technique with two aromatic compounds as sources of carbon was used. Effects of temperature and substrate concentration were studied. The mixed cultures retained their ability to degrade MCPA although the bacteria were grown for 3 months (32 successive passages) with glucose as the sole source of carbon and energy. With benzoic acid as co-substrate, one of the cultures was also able to degrade mecoprop and (+/-)2 (2, 4-dichloro)phenoxypropionic acid (dichlorprop). This ability was not maintained, however, over more than 10 passages. PMID- 24227134 TI - Interaction between an ammonium-oxidizer,Nitrosomonas sp., and two heterotrophic bacteria,Nocardia atlantica andPseudomonas sp.: A note. AB - Closed culture experiments showed that the ability of an estuarine chemolithotrophic ammonium-oxidizer,Nitrosomonas sp., to convert ammonium to nitrite was substantially increased by as much as 150% and 50% when grown in the presence of two heterotrophs isolated from the same environment. The heterotrophs were identified asNocardia atlantica andPseudomonas sp. The growth of the heterotrophs was stimulated by as much as one order of magnitude in the presence of the ammonium-oxidizer. PMID- 24227135 TI - Aerotaxis and chemotaxis ofAzospirillum brasilense: A note. AB - Azospirillum brasilense was attracted to capillaries containing either phosphate buffer, distilled water, or saline. The number of bacteria in these capillaries was 3-4*10(4), after 1 h of incubation. In the presence of phosphate buffer + attractants, the number of cells accumulated in the capillary increased only to 5*10(4)-1.1*10(5) cells. It was not possible, therefore, to measure chemotaxis inA. brasilense as distinct from aerotaxis by the capillary method. Chemotaxis was observed in semi-solid agar plates and was determined by a growth band oriented towards the attractant. Positive chemotactic response was obtained with peptone, tryptone, yeast extract, amino acids, organic acids, arabinose and galactose. PMID- 24227137 TI - Antibody responses in mice to particles formed from adsorption of a murine monoclonal antibody onto glass microparticles. AB - Immunogenicity of therapeutic monoclonal antibodies (mAbs) is a concern because of the effects of anti-drug antibodies (ADAs) on therapeutic efficacy. Particulate matter has been suggested as a potential contributing factor to immunogenicity. In this study, we investigated ADA levels in mice in response to administration of a murine immunoglobulin G (IgG)2c/kappa mAb (mAb1) that was generated in C57BL/6J mice. Particles of mAb1 were formed by adsorbing the protein to glass microparticles. Formulations containing microparticles were administered subcutaneously to mice of either the syngeneic strain, C57Bl/6J, or the allogeneic strain, BALB/c. ADA levels were measured using an isotype-specific enzyme-linked immunosorbent assay method. Whereas BALB/c mice showed strong IgG1 and IgG2b responses against both the particulate and native mAb1 samples, adsorption of mAb1 to particles rendered it slightly more immunogenic than its native, soluble form. In BALB/c mice, immunoglobulin M (IgM) was produced after the first week of injections and then faded gradually. In contrast, C57BL/6J mice showed moderate IgM, IgG1, IgG2b, and IgG3 responses to injections of glass particle-adsorbed mAb1. ADA responses were higher in the allogeneic BALB/c mice, which do not produce mAbs of the IgG2c/kappa isotype. Thus, the presence of both foreign epitopes and particles may be important in inducing ADA responses. PMID- 24227138 TI - Selection of somatic hybrids between diploid clones of potato (Solanum tuberosum L.) transformed by direct gene transfer. AB - Five diploid potato clones have been transformed by electroporation of protoplasts with different selectable markers. The resulting diploid regenerated plants have been used in somatic hybridization. It has been shown that hybrid cell selection on the basis of antibiotic or herbicide resistances brought by the two parents of fusion is an efficient method for the recovery of tetraploid somatic hybrids. PMID- 24227139 TI - Heavy metal tolerant transgenic Brassica napus L. and Nicotiana tabacum L. plants. AB - A chimeric gene containing a cloned human metallothionein-II (MT-II) processed gene was introduced into Brassica napus and Nicotiana tabacum cells on a disarmed Ti-plasmid of Agrobacterium tumefaciens. Transformants expressed MT protein as a Mendelian trait and in a constitutive manner. Seeds from self-fertilized transgenic plants were germinated on media containing toxic levels of cadmium and scored for tolerance/ susceptibility to this heavy metal. The growth of root and shoot of transformed seedlings was unaffected by up to 100 MUM CdCl2, whereas control seedlings showed severe inhibition of root and shoot growth and chlorosis of leaves. The results of these experiments indicate that agriculturally important plants such as B. napus can be genetically engineered for heavy metal tolerance/sequestration and eventually for partitioning of heavy metals in non consumed plant tissues. PMID- 24227140 TI - A simple, nondestructive spraying assay for the detection of an active kanamycin resistance gene in transgenic tomato plants. AB - A simple, nondestructive kanamycin spraying assay for detecting neomycin phosphotransferase II activity in tomato has been developed. This assay does not require the use of tissue culture or biochemical methods, but allows transgenic and non-transgenic tomato plants to be distinguished directly at the plant level in the green-house. Its potential applications in large-scale genetic analyses are discussed. PMID- 24227141 TI - A modified pedigree method of selection. AB - A dismal 81% failure of newly bulked lines against checks was observed in Indian wheat material evolved by the pedigree method. This is considered to be the consequence of selection in space planting in early generations followed by yield tests in a competitive environment which did not allow any scope of selection for competitive ability. Thus, most of the homozygous lines, which were until now raised and carried forward under space planting, failed to compete with the checks for yield in close planting. It is, therefore, necessary to modify the method to combine both the competitive ability and identity of selected plants. The proposed modified procedure involves raising the population under spaced planting as well as under drilling from F2 onwards. Evaluation for tiller index marks an important step. On the basis of tiller index, single plants are isolated from spaced populations. Steps of the modified procedure are outlined in detail. The modified method, which economises on breeders' workload and other physical inputs, besides having other advantages, can also be used for certain other grain crops. Preliminary results based on the modified method during the past two seasons have indicated its utility. PMID- 24227142 TI - Chromosomal location of gliadin coding genes in T. aestivum ssp. spelta and evidence on the lack of components controlled by Gli-2 loci in wheat aneuploids. AB - Electrophoretical analyses of the gliadin fraction extracted from seeds of the intervarietal substitution lines of T. aestivum ssp. spelta in the T. aestivum ssp. vulgare cv 'Chinese Spring' for the homoeologous groups 1 and 6 and substitution lines of 6D chromosome of 'Chinese Spring' in the durum wheat cv 'Langdon' allowed the identification of seeds without gliadin proteins controlled by genes on chromosome 6A and 6B. A gliadin component of 'Chinese Spring', not previously assigned to any specific chromosome, is controlled by chromosome 6D in the 6D (6A) and 6D (6B) disomic substitution lines of 'Langdon'. Additional genes controlling the synthesis of this component may be present on other chromosomes, very likely 6A and 6B, since the analysis of the 'Chinese Spring' compensating nullisomic-tetrasomics involving the 6D chromosome does not show the loss of this component or any apparent change in staining intensity. Chromosomal location data and two-dimensional gliadin maps reveal close homologies between the two hexaploid wheats, 'Chinese Spring' (T. aestivum ssp. vulgare) and T. aestivum ssp. spelta, belonging to different subspecies in the hexaploid group of genomic formula AABBDD. The comparison of gliadin electrophoretic patterns aiding in the identification of evolutionary pathways in wheat is stressed. PMID- 24227143 TI - Fate of introduced genetic markers in transformed root clones and regenerated plants of monohaploid and diploid potato genotypes. AB - Agrobacterium transformation of stem internodes of four monohaploid (839-79, 849 7, 851-23, 855-1) and two diploid (M9 and HH260) potato genotypes using hairy root-inducing single (LBA 1020, LBA 9365, LBA 9402) and binary (LBA 1060KG) vectors is reported. Various media and successive culture steps were tested for plant regeneration from different transformed root clones. The fate of introduced genetic markers in root clones and regenerated plants (hairy root phenotype, hormone autotrophy, opine production, kanamycin resistance, beta-glucuronidase activity), the ploidy stability and protoplast yield were analysed. The transformation efficiency of stem internodes (hairy root production) and the regeneration capacity of the transformed root clones greatly differed within and between the various potato genotypes. The regenerated plants obtained after transformation with both types of vectors often showed the absence of one or more genetic markers. However, transformation with the binary Agrobacterium vector generally resulted in the stable presence of the opines in all transformed root clones and most regenerated plants. In HH260, transformation efficiency, plant regeneration of transformed root clones, protoplast yield and ploidy stability were the highest as compared to the other genotypes. The application of these transformed plants as marker lines in gene mapping and gene expression studies is indicated. PMID- 24227144 TI - Incorporation of hygromycin resistance in Brassica nigra and its transfer to B. napus through asymmetric protoplast fusion. AB - With the idea to develop a selection system for asymmetric somatic hybrids between oilseed rape (Brassica napus) and black mustard (B. nigra), the marker gene hygromycin resistance was introduced in this last species by protoplast transformation with the disarmed Agrobacterium tumefaciens strain C58 pGV 3850 HPT. The B. nigra lines used for transformation had been previously selected for resistance to two important rape pathogens (Phoma lingam, Plasmodiophora brassicae). Asymmetric somatic hybrids were obtained through fusion of X-ray irradiated (mitotically inactivated) B. nigra protoplasts from transformed lines as donor with intact protoplasts of B. napus, using the hygromycin resistance as selection marker for fusion products. The somatic hybrids hitherto obtained expressed both hygromycin phosphotransferase and nopaline synthase genes. Previous experience with other plant species had demonstrated that besides the T DNA, other genes of the donor genome can be co-transferred. In this way, the produced hybrids constitute a valuable material for studying the possibility to transfer agronomically relevant characters - in our case, diseases resistances - through asymmetric protoplast fusion. PMID- 24227145 TI - Genome-specific repetitive sequences in the genus Oryza. AB - Repetitive DNA sequences are useful molecular markers for studying plant genome evolution and species divergence. In this paper, we report the isolation and characterization of four genome-type specific repetitive DNA sequences in the genus Oryza. Sequences specific to the AA, CC, EE or FF genome types are described. These genome-type specific repetitive sequences will be useful in classifying unknown species of wild or domestic rice, and in studying genome evolution at the molecular level. Using an AA genome-specific repetitive DNA sequence (pOs48) as a hybridization probe, considerable differences in its copy number were found among different varieties of Asian-cultivated rice (O. sativa) and other related species within the AA genome type. Thus, the relationship among some of the members of AA genome type can be deduced based on the degree of DNA sequence similarity of this repetitive sequence. PMID- 24227146 TI - Inheritance of potato aphid resistance in hybrids between Lycopersicon esculentum and L. pennellii. AB - The potato aphid, Macrosiphum euphorbiae Thomas, is an important pest of tomato, Lycopersicon esculentum Mill., because it transmits tomato viruses and directly reduces crop yields by its feeding. This study was conducted to determine whether the wild tomato species, Lycopersicon pennellii (Corr.) D'Arcy, would be useful as a source of potato aphid resistance for tomato. Type IV trichome density and aphid resistance were assessed in six generations (P1, P2, F1, F2, BC1P1, and BC1P2) from crosses between L. pennellii (LA 716) and two tomato cultivars, New Yorker and VF Vendor. Weighted leastsquares were used in joint scaling tests to estimate the relative importance of gene effects on type IV trichome density and potato aphid resistance of the hybrids. A simple additive-dominance model adequately explained the variation in type IV trichome density. Models which included digenic epistatic effects were required to explain the variation in aphid resistance. Standard unit heritability estimates of aphid resistance in the backcross to L. esculentum were obtained by regression of BC1F2 off-spring families on BC1F1 parents. Regression coefficients and heritability estimates varied between years with the level and uniformity of the aphid infestation. In the 1985-1986 growing seasons, when aphid infestations were uniform, aphid resistance exhibited a moderate level of heritability (29.8% +/- 14.1% and 47.1% +/- 11.5% in New Yorker and VF Vendor backcross populations, respectively). The non-uniform aphid infestation of 1984 resulted in lower heritability estimates in the 1984-1985 growing seasons (16.1% +/- 15.7% and 21.9% +/- 14.8% in the New Yorker and VF Vendor backcross populations, respectively). Selection for potato aphid resistance would probably be most efficient if it were delayed until gene combinations are fixed in later generations, because of the large epistatic effects and the low heritability of this trait in seasons with variable aphid infestations. PMID- 24227147 TI - Correlated responses in development and distribution of fat depots in mice selected for body composition traits. AB - Development of adipose tissue in five depots was investigated in mice selected for high or low 12-week epididymal fat pad weight as a percentage of body weight (HF and LF lines), or high or low 12-week hind carcass weight as a percentage of body weight (HL and LL lines). An unselected control line (RC) was maintained. Hind carcass (HC) and fat pads from subcutaneous hindlimb, subcutaneous forelimb, gonads, kidneys and mesentery were dissected and weighed at 4, 6, 9, 12 or 15 weeks of age. Generally, body weight (BW), daily gain (DG), feed intake (FI), feed efficiency (FE) and feed intake/metabolic body weight (FC) were higher (P<=0.05) in HF than in LF, and in LL than in HL. HF had more fat (as a percentage of BW) than LF in all depots (P?-0.01), and asymmetry (P<=0.01) was detected for gonadal fat. LL consistently had a higher (P<=0.01) fat percentage than HL, and asymmetry (P<=0.01) was observed for perirenal fat. At age of selection, ranking of fat depot weights as a percentage of total fat depot weight was not changed by selection; however, gonadal fat accounted for more of the total fat in HF and LL compared with RC, while the opposite was found in LF and HL. HC percentage was higher (P<=0.01) in HL than LL, and higher (P<=0.01) in LF than HF. Growth rate of each fat depot relative to BW was not affected by selection. These results demonstrated that selection for proportion of fat in one depot or for HC percentage changed fat percentage in other depots. However, the rate of fat deposition in each depot relative to body weight gain was not altered. PMID- 24227148 TI - Association of four isozyme loci with a reciprocal translocation between 1R/4R chromosomes in cultivated rye (Secale cereale L.). AB - The progeny of four crosses between a structural heterozygote for a reciprocal translocation and a homozygote for the standard chromosome arrangement were analyzed in rye (Secale cereale L. cv "Ailes") for the electrophoretic patterns of eight different leaf and endosperm isozymes and also for the meiotic configuration at metaphase I. The Pgi-1, 6-Pgd-2 and Mdh-1 loci are linked to each other and also to the reciprocal translocation. These loci have been located on chromosome 1R. The Mdh-1 locus is located in the interstitial segment of chromosome 1R, between the centromere and the breakpoint. The Pgm-1 locus has been located on chromosome arm 4RS and is linked to Pgi-1, 6-Pgd-2, Mdh-1 and the reciprocal translocation. The estimated distance between the Pgm-1 locus and the centromere is 14.98 +/- 2.27 cM. Therefore, the reciprocal translocation involves the 1R and 4R chromosomes. Other linked loci detected have been Mdh-2b and Est-2 (7.40 +/- 2.90 cM) and Got-3 and Est-2 (5.62 +/- 3.07 cM). These three last loci are located on chromosome 3R and their order most probably is Mdh-2b - Est-2 - Got-3. PMID- 24227149 TI - Mechanism of durable resistance: a new approach. AB - Wheat genotypes, including backcross derivatives of 'Thatcher' carrying Lr10 and Lr23, substitution lines for Lr10 and Lr23 in Chinese Spring background and Chinese Spring and Thatcher were analysed against 21 pathotypes of leaf rust in seedling tests. Adult plant responses in all these stocks were observed in the field nurseries under exposure to the inoculum of the Indian virulent races of leaf rust. The seedling data demonstrated that both the substitution lines and the backcross derivatives for each gene carry identical pattern of infection for resistance. The high level of adult plant resistance in the substitution lines, in contrast to the backcross derivatives in Thatcher, has been postulated to be due to the combination of resistance contributed by Lr10 and adult plant Chinese Spring resistance or to Lr23 and Chinese Spring adult plant resistance. It has been suggested that genes Lr10 and Lr23 added to the Chinese Spring background provide sources for durable resistance, since Chinese Spring has continued to provide a moderate level of adult plant resistance to leaf rust for a very long time. PMID- 24227150 TI - Some aspects of autotetraploid population dynamics. AB - Self-compatible autotetraploids are likely to set much of their seed by selfing. Formulae are presented for the frequencies in any generation of states of loci, from homozygous to quadri-allelic, considering the frequencies of selfing and of double reduction but not allowing for the effects of inbreeding depression on population structure. The changing structure of populations over generations is also explored by computer simulation, incorporating selection against inbreds but ignoring double reduction. The findings are discussed in relation to mass selection programmes. PMID- 24227151 TI - Environmental sensitivity and heterosis for egg laying in Drosophila melanogaster. AB - Genotype * temperature interactions for egg laying were studied in Drosophila melanogaster using two sets of half diallel crosses: one between inbred lines of the same geographic origin, and the other between established laboratory, newly derived inbred lines from different geographic origins. The sensitivity of most genotypes to changes in temperature was adequately described as a linear regression of mean in temperature. The regression coefficients (linear sensitivities) were heterogeneous between genotypes. Hybrids were more affected by temperature variation than were inbreds. All the heterogeneity of linear sensitivities was accounted for by a linear function of the genotypic means, which strongly suggests that a scale effect is responsible for the differences in sensitivity to temperature. In contrast, no general relationship was found between standard error deviation (sensitivity to small environmental changes) and mean performance between genotypes, although hybrids tended to be less variable than inbreds. This shows that the sensitivity to environmental variation depends not only on the genotype, but also on the nature of the environmental variation. The variability within temperatures may be affected by the general homeostasis of individual genotypes, while the variability between temperatures could be the result of genes directly affecting the trait and their multiplicative interaction with the environment. PMID- 24227152 TI - Cytogenetic studies of Haplopappus gracilis in both callus and suspension cell cultures. AB - Investigations have been carried out on karyotype change in both callus and suspension cell cultures of Haplopappus gracilis (2n=4). It has been found that polyploidization arises directly in culture to give up to six times the normal diploid chromosome number in some cultures. In polyploid cultures, both chromosome loss and chromosome rearrangements occur to give rise to aneuploid karyotypes displaying chromosomes which differ in morphology from the diploid set. Whole or partial chromosome loss has been observed in the form of lagging chromosomes and chromosome bridges at anaphase, and micronuclei, ring chromosomes and chromosome fragments at other stages in mitosis. C-banded preparations have confirmed the occurrence of chromosomal rearrangements. Comparative investigations suggest that (i) more polyploidy occurs in callus cultures than in suspension cell cultures, and (ii) the presence of cytokinin (kinetin) in the culture medium may reduce the extent of karyotype change. PMID- 24227153 TI - Genetic diversity in wild diploid wheats Triticum monococcum var. boeoticum and T. urartu (Poaceae). AB - The genetic diversity of two wild diploid wheat species, Triticum monococcum var. boeoticum and T. urartu, was assessed using starch gel electrophoresis. Genetic diversity is uniformly low in both species. Number of alleles per locus was very low with a mean of 1.22 for T. monococcum var. boeoticum and 1.19 in T. urartu. Percentage of polymorphic loci was also low, with a mean of 19.71 for T. monococcum var. boeoticum and a mean of 18.35 for T. urartu. Mean gene diversity was low with a mean of 0.052 in populations of T. monococcum var. boeoticum and a mean of 0.040 in populations of T. urartu. Genetic affinities of the species and of populations were computed using Nei's identity index (NI). Overall genetic affinities of the two species are NI=0.697. The genetic affinities of different populations of a species are uniformly high with NIs ranging from 0.894 to 1.000 in T. monococcum var. boeoticum and from 0.898 to 1.000 in T. urartu. PMID- 24227154 TI - In vitro selection for 2,4-D tolerance in red clover. AB - In vitro, selection is a viable method of selecting herbicide-tolerant crops. This research was to evaluate in vitro selection techniques for enhancing 2,4-D [(2,4-dichlorophenoxy) acetic acid] tolerance in red clover (Trifolium pratense L.). In vivo and in vitro responses to 2,4-D of eight diverse red clover populations were correlated (r=0.77), justifying in vitro selection for 2,4-D tolerance. Suspension cultures of a red clover genotype capable of regeneration were plated onto agar-based nutrient media supplemented with 0.18 mM 2,4-D for selection experiments. After two cycles of selection, 16 2,4-D tolerant callus lines were identified based on visual growth assessment. These lines were evaluated for 2,4-D tolerance (based on 2,4-D content), using a 2,4-D bioassay procedure which consisted of placing selected callus tissue pieces on top of oat (Avena sativa L.) coleoptile or internode sections. The relative amount of 2,4-D in the callus tissue was estimated by the amount of oat section elongation after 24 h. Two of the more tolerant callus lines had 61% and 83% less 2,4-D in their tissues than the susceptible control tissue. These studies indicated that in vitro selection can enhance the levels of 2,4-D tolerance in red clover callus tissue. PMID- 24227155 TI - Atrazine-resistant cauliflower obtained by somatic hybridization between Brassica oleracea and ATR-B. napus. AB - Somatic hybridization between Brassica oleracea ssp. botrytis (cauliflower, 2n=18), carrying the Ogura (R1) male-sterile cytoplasm and B. napus (2n= 38), carrying a male-fertile, atrazine-resistant (ATR) cytoplasm, yielded three hybrids (2n=56) and six cauliflower cybrids (2n=18), which were selected for resistance to the herbicide in vitro. The hybrids and cybrids were male fertile and self-compatible. They contained both chloroplasts and mitochondria from the ATR cytoplasm. We found no evidence for mtDNA recombination in any of the regenerated plants. Selfed progeny of the B. oleracea atrazine-resistant cybrids were evaluated for tolerance to the herbicide in the field. Resistant plants exposed to 0.56-4.48 kg/ha (0.5-4.0 pounds/acre) atrazine in the soil showed no damage at any herbicide level, whereas plants of a susceptible alloplasmic line were severely damaged at the lowest level of herbicide application and killed at all higher levels. These atrazine-resistant cauliflower may have potential horticultural use, especially in fields where atrazine carry over is a serious problem. PMID- 24227156 TI - Genetic diversity of six isozyme loci in cultivated barley of Tibet. AB - A random sample of 463 accessions of cultivated barley from the Tibet Hordeum germplasm collection was assayed electorphoretically for genetic diversity at six isozyme loci. Two loci (Acp-1 and Got-1) were found to be monomorphic and extensive variation was detected at the remaining four loci (Est-1, Est-2, Est-3 and Est-4). The allelic composition of Tibetan barley appeared to be distinct as compared to the results of previous studies of barleys from other parts of the world. Partitioning of genetic diversity showed that approximately 96% of the total variation was maintained at the within-subregion level and only about 4% was accounted for by differentiation among the eight subregions. Analysis of multilocus genotypes revealed non-random association of the alleles at the four loci, both in the entire sample and in all the subregions, although the four major multilocus genotypes did not show significant departure from the expectation based on complete random association. The possible causes for the establishment of these multilocus associations were discussed. PMID- 24227157 TI - PEG- and electroporation-induced transformation in Nicotiana tabacum: influence of genotype on transformation frequencies. AB - Experimental parameters for direct gene transfer with recombinant DNA encoding neomycin phosphotransferase II (NPTII) under control of eukaryotic expression signals were established. The introduced gene was shown by the growth of transformants on media containing kanamycin, by genomic blotting and by assaying NPTII activity. Leaf protoplasts from three green genotypes of varieties xanthii and petit havanna, and from four plastome-encoded albino genotypes of Nicotiana tabacum were analyzed with respect to cell division kinetics and yield of kanamycin-tolerant colonies after direct gene transfer. No clear correlation was found between the time of onset of cell division and transformation frequency. PMID- 24227158 TI - A new cytoplasmic male sterile genotype in the sugar beet Beta vulgaris L.: a molecular analysis. AB - Mitochondrial DNA (mtDNA) from fertile (N) and possibly new cytoplasmic male sterile (CMS) genotypes was studied in the sugar beet Beta vulgaris L. It was found by restriction endonuclease analysis that BMC-CMS, a cytoplasm that was derived from the wild beet Beta maritima, contained a unique type of mtDNA which is distinguishable from both the N and S-CMS, the only other CMS genotype that is currently availabe in B. vulgaris L. The organization of three genes: coxI, coxII and cob, was analyzed by hybridization with heterologous probes from maize. These genes have a similar structure in N and BMC-CMS that is different from S-CMS. It is concluded that BMC-CMS is a novel CMS genotype in the sugar beet. PMID- 24227159 TI - Effect of selection intensity and population size on percent oil in maize, Zea mays L. AB - The effect of selection intensity and population size on the response to selection for percent oil in the grain of maize (Zea mays L.) was evaluated in a replicated experiment over ten cycles of selection. An open-pollinated variety, Armel's Reid Yellow Dent, was divided into subpopulations of 6,10 and 50 plants. Selection proportions of 17% and 5% were imposed upon each subpopulation. Selection was based on the percentage of oil in individual kernels as determined by wide-line nuclear magnetic resonance spectroscopy. As expected, total response to selection increased with larger population sizes and selection intensities. The concave shape of the response curves suggested that an appreciable part of the genetic variance can be attributed to additive genes at high initial frequencies, dominance genes at low initial frequencies, or to the generation of negative linkage disequilibrium due to selection. The consistently greater loss of vigor experienced by the more intensely selected populations reflects the enhancement of inbreeding due to artificial selection, an effect that increases with the intensity of selection. The results indicate that combined selection, based on kernels and using within- and amongfamily information, will be more efficient than other conventional selection procedures, including the normal combined scheme where selection is based on plants. PMID- 24227160 TI - Oxidative addition of disulfide/diselenide to group 10 metal(0) and in situ functionalization to form neutral thiasalen/selenasalen group 10 metal(II) complexes. AB - Three components, one pot synthesis of thiasalen/selenasalen Ni(II), Pd(II) and Pt(II) complexes, 14-19, by the oxidative addition of S-S/Se-Se bond of bis(o formylphenyl)disulfide/-diselenide to Ni(0), Pd(0) and Pt(0) followed by in situ Schiff base formation with ethylenediamine is reported. S-S or Se-Se bonds were cleaved and coordinated to the metal center as thiolate (ArS(-)) or selenolate (ArSe(-)) while the formal oxidation state of metal centers was changed from '0' to '+2'. The disulfide/diselenide reacted with zero-valent metals at room temperature to give only the monometallic complexes. All complexes (except Pd thiolate complex 15) were studied by single crystal X-ray crystallography and revealed the square planar geometry around metal centers. PMID- 24227162 TI - Micellar control of the photooxidation pathways of 10-methyl phenothiazine: electron versus energy transfer mechanisms. AB - 10-Methyl phenothiazine (MPS) was chosen as a model compound to investigate the effects of compartmentalisation and of charged interfaces on the primary mechanisms involved in the phototoxic reactions related to phenothiazine drugs. Two most important pathways resulting from the interaction of the triplet excited state of MPS ((3)MPS*) with molecular oxygen ((3)O2) have to be considered: (i) energy transfer producing singlet oxygen ((1)O2) and (ii) electron transfer generating the superoxide anion (O2(-)) and the radical cation (MPS(+)). The quantum yields of (1)O2 production by MPS solubilized in the dispersed pseudo phase of aqueous micellar systems were found to be similar to those determined in solvents of various polarities, regardless of the anionic or cationic nature of the surfactant (SDS or CTAC). However, micellar compartmentalisation and surfactant charge affect considerably both the sensitized and the self-sensitized photooxidation of MPS. The formation of 10-methyl phenothiazine sulfoxide (MPSO), produced by the reaction of MPS with (1)O2, proceeds at a higher rate in SDS micelles than in neat polar solvents. This result may be explained by the protonation of the zwitterionic intermediate Z (MPS(+)OO(-)) at the micellar interface to yield the corresponding cation C (MPS(+)OOH) that is stabilized in the negatively charged micelles and reacts much faster with MPS than Z to yield MPSO. The electron transfer reaction from (3)MPS* to O2 yielding MPS(+) and O2(-) is also enhanced in SDS micelles, as back electron transfer (BET) is prevented by ejection of O2(-) to the aqueous bulk phase and stabilization of MPS(+) in the anionic micelles. The size of the SDS micelles modulates the relative contribution of each pathway (formation of MPSO or MPS(+)) to the overall conversion of MPS to its oxidation products. Photooxidation of MPS in cationic micelles is a very slow process, as the formation of neither C nor MPS(+) is favoured in positively charged micelles. PMID- 24227161 TI - Investigating biocomplexity through the agent-based paradigm. AB - Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machines--or agents--to simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex. PMID- 24227163 TI - Tooth cusp sharpness as a dietary correlate in great apes. AB - Mammalian molars have undergone heavy scrutiny to determine correlates between morphology and diet. Here, the relationship between one aspect of occlusal morphology, tooth cusp radius of curvature (RoC), and two broad dietary categories, folivory and frugivory, is analyzed in apes. The author hypothesizes that there is a relationship between tooth cusp RoC and diet, and that folivores have sharper teeth than frugivores, and further test the correlation between tooth cusp RoC and tooth cusp size. Eight measures of tooth cusp RoC (two RoCs per cusp) were taken from 53 M(2) s from four species and subspecies of frugivorous apes (Pongo pygmaeus, Pan troglodytes troglodytes, Pan troglodytes schweinfurthii, and Gorilla gorilla gorilla) and two subspecies of folivorous apes (Gorilla beringei beringei, and Gorilla beringei graueri). Phylogenetically corrected ANOVAs were run on the full dataset and several subsets of the full dataset, revealing that, when buccolingual RoCs are taken into account, tooth cusp RoCs can successfully differentiate folivores and frugivores. PCAs revealed that folivores consistently had duller teeth than frugivores. In addition, a weak, statistically significant positive correlation exists between tooth cusp size and tooth cusp RoC. The author hypothesizes differences in tooth cusp RoC are correlated with wear rates, where, per vertical unit of wear, duller cusps will have a longer length of exposed enamel ridge than sharper cusps. More data need to be gathered to determine if the correlation between tooth cusp RoC and tooth cusp size holds true when small primates are considered. PMID- 24227164 TI - A highly active perovskite electrode for the oxygen reduction reaction below 600 degrees C. PMID- 24227165 TI - Highly asymmetrical porphyrins with enhanced push-pull character for dye sensitized solar cells. AB - A porphyrin pi-system has been modulated by enhancing the push-pull character with highly asymmetrical substitution for dye-sensitized solar cells for the first time. Namely, both two diarylamino moieties as a strong electron-donating group and one carboxyphenylethynyl moiety as a strong electron-withdrawing, anchoring group were introduced into the meso-positions of the porphyrin core in a lower symmetrical manner. As a result of the improved light-harvesting property as well as high electron distribution in the anchoring group of LUMO, a push-pull enhanced, porphyrin-sensitized solar cell exhibited more than 10% power conversion efficiency, which exceeded that of a representative highly efficient porphyrin (i.e., YD2)-sensitized solar cell under optimized conditions. The rational molecular design concept based on highly asymmetric, push-pull substitution will open the possibilities of further improving cell performance in organic solar cells. PMID- 24227166 TI - Somatic hybrid plants produced by electrofusion between dihaploid potatoes: BF15 (H1), Aminca (H6) and Cardinal (H3). AB - In order to regenerate somatic hybrids, mesophyll protoplasts from a dihaploid potato, BF15 (H1), were electrofused with those from two other dihaploid clones, Aminca (H6) and Cardinal (H3). Determination of the ploidy level by flow cytometry showed that 10% of plants regenerated from the fusion experiment with "BF15 + Aminca" were diploids, 14% triploids, 63% tetraploids and very few were mixoploids or had a higher ploidy level. Using morphological markers and vigour in plant growth, we were able to recover a total of 24 somatic hybrid plants, respectively 20 and 4 hybrids (accounting for 12% and 13% of regenerants) from the fusions "BF15 + Aminca" and "BF15 + Cardinal". Most of the somatic hybrids were at the expected tetraploid level (2n=4x=48). The hybrid nature was confirmed by examining isoenzyme patterns for malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICD). PMID- 24227167 TI - Silicon carbide fiber-mediated DNA delivery into plant cells. AB - Silicon carbide fiber-mediated delivery of DNA into intact plant cells was investigated. Black Mexican Sweet (BMS) maize (Zea mays) and tobacco (Nicotiana tabacum) suspension culture cells were vortexed in the presence of liquid medium, plasmid DNA encoding beta-glucuronidase (GUS), and silicon carbide fibers. Penetration of BMS cells by the silicon carbide fibers was observed by scanning electron microscopy of vortexed cells. Following fiber and DNA treatment, BMS cells transiently expressed GUS activity at a mean frequency of 139.5 units (one unit = one blue cell or one colony of blue cells) per sample. Treated tobacco cells expressed an average of 373 GUS units per sample. Untreated controls did not exhibit GUS activity. These results indicate that the silicon carbide fibers vortex procedure can be used to rapidly and inexpensively deliver foreign DNA into intact plant cells for investigations of transient gene expression. PMID- 24227168 TI - Plant regeneration from a cryopreserved embryogenic cell suspension of a commercial sugarcane hybrid (Saccharum sp.). AB - Efficient plant regeneration was obtained from a cryopreserved embryogenic cell suspension of sugarcane established from leaf derived callus. Pregrowing the cells for three days in MS basal medium supplemented with 0.33 M sorbitol was essential to the process. The cells were cooled at a rate of 0.5 degrees C/min to -40 degrees C and then stored in liquid nitrogen. Thawing was carried out rapidly in water at +40 degrees C, and the cells were then plated without washing onto filter paper discs placed on a semi-solid regeneration medium (MS basal + 3% sucrose + 0.13 mg/1 2,4-D +0.25 mg/1 BAP + 0.25 mg/1 kinetin + 0.25 mg/1 zeatin). The filter paper discs, along with the cells, were transferred to the same, fresh medium after five hours. After 24 hours the cells were scraped off, placed on fresh semi-solid medium and incubated at 28 degrees C in the dark for two weeks before transfer to light. A regeneration efficiency of 92% was obtained (regenerated plants, expressed as a percent of unfrozen control). Plants regenerated from cryopreserved cells, and grown to maturity in the greenhouse, were morphologically identical to regenerated control plants. PMID- 24227169 TI - Immobilization of cells of Nicotiana tabacum L. on polyphenyleneoxide coated with poly-L-lysine. AB - Cells of Nicotiana tabacum L. cv. Wisconsin 38 were immobilized on poly (2,6 dimethyl)-p-phenyleneoxide in powder form (Sorfix) coated with poly-L-lysine (molecular weight 40 000 daltons). The dependence of cell immobilization on the amount of bound polyL-lysine was estimated. PMID- 24227170 TI - Plant regeneration from callus and protoplasts of Brassica nigra (IC 257) through somatic embryogenesis. AB - A method to obtain plants from embryogenic callus of Brassica nigra and protoplasts of hypocotyl expiants is described. Callus was initiated on Murashige and Skoog medium containing kinetin (kn) and 2,4-dichlorophenoxy acetic acid (2,4 D). Lowering of auxin induced embryo formation. Supplementation with gibberellic acid (GA3) enhanced embryogenic response tenfold. Passage through liquid medium devoid of growth regulators was essential for the growth of embryos. Secondary embryos were produced on transfer to solid basal medium. Embryogenic callus retained its morphogenic ability even after 12 subcultures. Both primary and secondary embryos produced fertile plants. Hypocotyl-derived protoplasts were also regenerated to plants following the same protocol. The survival of plants on transfer to soil was about 80%. The seeds from plants derived from callus and protoplasts were viable. PMID- 24227171 TI - In vitro propagation of the bamboo (Bambusa tulda Roxb.) through shoot proliferation. AB - An efficient protocol has been developed for the in vitro propagation of Bambusa tulda through shoot proliferation. Shoots from 3-week-old aseptically grown seedlings were used to initiate cultures. Multiple shoots were obtained on liquid Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (8*10(-6)M) and kinetin (4*10(-6)M). Continuous shoot proliferation at a rate of 4-5 fold every three weeks was achieved through forced axillary branching. More than 90% of the shoots could be rooted on a modified MS medium containing indoleacetic acid (1*10(-5)M) and coumarin (6.8*10(-5)M). Following simple hardening procedures, the in vitro raised plants were transferred to the soil with more than 80% success. PMID- 24227172 TI - Phytochrome-mediated swelling of etiolated leaf protoplasts and its possible biological significance. AB - Red light, mediated by the photoreceptor phytochrome, induces maize leaf unrolling as well as leaf expansion. Protoplasts prepared from maize leaves still in the rolled condition swell in a red-far red photoreversible manner indicating that phytochrome mediates this phenomenon. To determine if protoplast swelling is related to leaf unrolling, leaf expansion, or both, we compared red-light induced swelling of protoplasts from rolled maize leaves to protoplasts prepared from tissues that are known to grow in response to light but do not unroll. We also compared the swelling response of protoplasts from rolled vs. unrolled leaves. In all cases, we found that swelling correlated with the unrolling response and not leaf expansion. PMID- 24227173 TI - Rapid mass propagation of Chrysanthemum morifolium by callus derived from stem and leaf explants. AB - A procedure for rapid multiplication of Chrysanthemum morifolium RAMAT cv. Birbal Sahni using leaf callus and stem (nodal/internodal) callus as well as node and apical shoots has been developed. Murashige and Skoog's medium (1962) supplemented with 2mg/1 2,4-D yielded good green calli from both leaf and stem segments within 2 weeks. About 1 cm * 1 cm callus regenerated 2-3 shoots after 3 weeks on MS solid medium supplemented with 0.1 mg/l IAA and 0.2 mg/l BAP. Each of the regenerated shoots when transferred to the same shooting medium without agar yielded about 150 new shoots, which in turn regenerated roots after another week in MS half strength or modified White's media (Rangaswamy, 1961). It has been estimated that about 10(14) plantlets could be produced in a year from one expiant following the proposed protocol. PMID- 24227174 TI - Plant regeneration through somatic embryogenesis in the forage grass Caucasian bluestem (Bothriochloa caucasica). AB - Plantlets were regenerated from cultured seed explants of the forage grass Caucasian bluestem [Bothriochloa caucasica (Trin.) C.E. Hubbard] via somatic embryogenesis. Embryogenic callus was produced in four weeks when surface sterilized seeds were cultured on a medium containing MS-salts, B-5 vitamins, 12 mM L-proline, 2% sucrose, 0.8% agar and 5MUM 2,4-D. Plantlets were regenerated in 6-8 weeks after culture initiation. Healthy root and shoot systems were produced within three weeks after the plantlets were transferred to a medium lacking 2,4 D. Approximately 95% of the plantlets survived greenhouse acclimation and produced healthy plants and viable seeds. Caucasian bluestem callus cultures exhibit natural resistance to kanamycin. High levels of kanamycin (up to 800 mg/l) did not completely inhibit callus growth. However, the regeneration of healthy-plantlets was completely inhibited by kanamycin even at low levels (50 mg/l). PMID- 24227175 TI - Plant regeneration from leaf and seed-derived calli and suspension cultures of the African perennial wild rice, Oryza longistaminata. AB - Plant regeneration from 2-month-old callus cultures derived from immature leaves of 7-day-old aseptic seedlings and mature embryos of the African wild rice Oryza longistaminata was achieved at 20% and 100% frequency, respectively. The morphogenic potential of the embryo-derived calluses dropped from 100% at the third subculture to 12.5 % at the 12th subculture. Five-month-old morphogenic calluses were used to establish a fast-growing suspension culture which, when plated onto semisolid medium, still retained its ability to regenerate plantlets 9 months after initiation. Histological analyses demonstrated that late plant regeneration from established callus and suspension cultures occured through organogenesis, although some embryogenesis events may have taken place during initiation of these cultures. PMID- 24227176 TI - Manipulating the desiccation tolerance and vigor of dry somatic embryos of Medicago sativa L. with sucrose, heat shock and abscisic acid. AB - The effects of sucrose concentration in the maturation medium in combination with a heat shock treatment at 36 degrees C were investigated in an attempt to improve the vigor of seedlings grown from dry somatic embryos of alfalfa (Medicago sativa L.). Callus was formed from petiole expiants and dispersed in liquid suspension medium in the presence of 5 MUM 2,4-D. The cell suspension was sieved to synchronize embryo development. The 200 - 500 MUm fraction was plated on embryo development medium without 2,4-D, grown for 14 days, and transferred to maturation medium. With 3% sucrose in the maturation medium, the somatic embryos germinated precociously and were unable to survive desiccation. At higher sucrose concentrations, germination was delayed and the embryos continued to accumulate dry matter. After 13 days on 6% sucrose medium (27 days after sieving), the somatic embryos were tolerant of drying to 12% moisture without exposure to exogenous ABA. Heat shock, which presumably stimulates endogenous ABA synthesis, improved the desiccation tolerance of somatic embryos if applied prior to day 27 after sieving, but its effects were minimal after day 27. High sucrose concentrations up to 9% in the maturation medium were optimal during the first 8 days on maturation medium (days 14 to 22 after sieving), but a lower concentration (6%) was optimal during the later stages of embryo maturation (days 22 to 30 after sieving). The inclusion of 10(-5) M ABA in the maturation medium with 6% sucrose further improved embryo quality if applied approximately 20 days after sieving. PMID- 24227177 TI - Somatic embryogenesis and regeneration of flowering plants in rose. AB - Somatic embryos of the cut rose cultivars 'Domingo' and 'Vickey Brown' were obtained from callus derived from leaf explants on half strength Murashige and Skoog medium with low concentrations of kinetin and 1-naphthyl acetic acid or 2 naphthyloxyacetic acid. Somatic embryos were first observed after 6 to 12 weeks of culture on callus formed at the basis or midrib of the leaf. Embryos could be grown to phenotypically true to type greenhouse plants. PMID- 24227178 TI - Induction of callus from axillary buds of taro (Colocasia esculenta var. esculenta, Araceae) and subsequent plantlet regeneration. AB - Axillary buds of taro (Colocasia esculenta var. esculenta, Araceae) cultured on half strength Murashige-Skoog medium (HMS) containing taro extract (HMSTE) and 2, 4, 5-trichlorophenoxyacetic acid produce a compact, hard, slow growing callus which is not very active morphogenetically and produces only a few plantlets. When cultured on HMSTE plus 5 mg 1(-1) each of naphthaleneacetic acid and benzyl adenine (HMSNB) the buds produce a fast growing, friable and morphogenetically active callus. Meristematic regions form on the friable callus after 30 days on HMSNB. If transferred to HMSTE at this point the callus gives rise to plantlets. Addition of taro extract to the media is required for the culture of buds, induction of callus and plantlet regeneration. PMID- 24227179 TI - Establishing axenic cultures from mature pecan embryo explants on media with low water availability. AB - Endophytic fungi associated with mature pecan (Carya illinoensis (Wangenh.) C. Koch) nuts prevented successful, contaminant-free in vitro culture of embryo expiants, even after rigorous surface disinfestation of the nuts and careful aseptic shelling. Disinfestation with sodium hypochlorite after shell removal was also unsuccessful, because even dilute concentrations which were ineffective against the fungal contaminants prevented subsequent growth from the embryo. Explanting media with low water availability which would not sustain growth of fungal contaminants, but supported growth from mature pecan embryos, were developed as an alternative disinfestation method. The explanting media were supplemented with 0.9-1.5% agar, and other media components were selectively omitted to test their influence on water availability and fungal growth. Disinfestation of up to 65% of the cultures was accomplished, depending on the medium formulation, compared to 100% loss to contamination on control medium (0.5% agar). A complete medium (containing sucrose, salts, vitamins, 18 MUM BAP, and 5 MUM IBA) with 1.5% agar provided control of contamination, and encouraged subsequent regeneration from the embryo expiants, which remained free of contaminant growth through subsequent subcultures. PMID- 24227180 TI - Phytochelatin accumulation and stress tolerance in tomato cells exposed to cadmium. AB - Cell suspension cultures of tomato (Lycopersicon esculentum) adapted to growing continuously in the presence of 0.1 mM CdCl2 and accumulated phytochelatins (PCs, poly(gamma-Glu-Cys)n-Gly). The highest level of PCs was measured 4 days after inoculation and coincided with the peak of cellular cadmium concentration. At this time there was an 8-fold molar excess of PC (gamma-Glu-Cys) over Cd. PCs could not be detected after 12 days when the cellular concentration of cadmium was 0.2 mM. These results indicate that PCs are produced in excess of that required to bind the cellular cadmium in the early stage of the culture period followed by degradation of PCs during the stationary phase. Adaptation to 0.1 mM CdCl2 did not increase tolerance to higher concentrations of cadmium when compared with control cells, but did significantly enhance tolerance to both anaerobiosis and heat shock. Exposure of tomato cells to 0.1 mM CdCl2 resulted in several changes in proteins synthesized. PMID- 24227181 TI - Strategies for sustaining self used by family caregivers for older adults with dementia. AB - The negative health consequences of caring for an older adult family member with dementia are well documented. However, not all family caregivers experience these negative health consequences. The purposes of this study were to describe strategies family caregivers use to help them continue to provide care for an older family member with dementia despite challenges and describe these family caregivers' resilience and psychological distress. A mixed methods design was used with a narrative approach dominant and standardized scales for resilience and psychological distress used to enhance the description of the sample. Data were collected through telephone interviews with 18 family caregivers residing in an urban area. The findings indicate that family caregivers used four strategies to sustain the self: drawing on past life experiences, nourishing the self, relying on spirituality, and seeking information about dementia. Understanding strategies used by family caregivers to sustain themselves is essential for providing holistic nursing care and developing effective interventions. PMID- 24227182 TI - Longitudinal pattern of depressive symptoms around natural menopause. AB - IMPORTANCE: An increased risk of depressive symptoms has been associated with the transition to menopause, but the risk of depressive symptoms in the early postmenopausal years has not been well characterized. OBJECTIVES: To identify within-woman changes in depressive symptoms during a 14-year period around menopause, determine associations of a history of depression with the pattern of depressive symptoms, and evaluate the rate of change in reproductive hormones as predictors of depressive symptoms following menopause. DESIGN, SETTING, AND PARTICIPANTS: A randomly identified, population-based sample in Philadelphia County, Pennsylvania, of 203 late-reproductive-age women who were premenopausal at baseline and reached natural menopause. MAIN OUTCOMES AND MEASURES: Center for Epidemiologic Studies Depression Scale. RESULTS: The prevalence of high scores on the Center for Epidemiologic Studies Depression Scale decreased from 10 years before to 8 years after the final menstrual period (FMP), with a decrease of approximately 15% of baseline per year (odds ratio, 0.85; 95% CI, 0.81-0.89; P < .001). Relative to the FMP, the risk of depressive symptoms was higher in the years before and lower in the years after the FMP. Among women with a history of depression, the likelihood of depressive symptoms was more than 13 times greater overall and 8 times greater after menopause compared with women with no depression history. Among women who first experienced depressive symptoms approaching menopause, the risk of depressive symptoms declined after the FMP, with a significantly lower risk the second year after menopause. The risk of depressive symptoms after menopause decreased by 35% for each unit (SD) increase before the FMP in the log rate of change of follicle-stimulating hormone (odds ratio, 0.65; 95% CI, 0.46-0.91; P = .01). CONCLUSIONS AND RELEVANCE: The FMP was pivotal in the overall pattern of decreasing depressive symptoms in midlife women, with higher risk before and lower risk after the FMP. A history of depression strongly increased the risk both before and after menopause. Women who had no history of depression before the menopause transition had a low risk of depressive symptoms 2 or more years after the FMP. PMID- 24227183 TI - Level of physical activity associated with risk of cardiovascular diseases and mortality in patients with type-2 diabetes: report from the Swedish National Diabetes Register. AB - AIMS: To estimate risks of coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality with low or higher levels of physical activity (PA) assessed with questionnaire, in an observational study of patients with type-2 diabetes from the Swedish National Diabetes Register. SUBJECTS AND METHODS: A total of 15,462 patients (60 years), were followed for 5 years from baseline in 2004 until 2009, with 760 CVD events and 427 total mortality events based on 54,344 person-years. RESULTS: Comparing 6963 patients with low baseline PA (never or 1-2 times/week for 30 min) and 8499 patients with higher baseline PA (regular 3 times/week or more), hazard ratios for fatal/nonfatal CHD, fatal/nonfatal CVD, fatal CVD, and total mortality were 1.25 (95% CI 1.05-1.48; p = 0.01), 1.26 (95% CI 1.09-1.45; p = 0.002), 1.69 (95% CI 1.18-2.41; p = 0.004), and 1.48 (95% CI 1.22-1.79; p < 0.001), adjusting for age, sex, diabetes duration, diabetes treatment, and smoking (model 1). Adjusting also for HbA1c, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides, body mass index, and albuminuria (model 2), HRs were 1.19 (95% CI 1.00-1.42; p = 0.049), 1.18 (95% CI 1.02-1.36; p = 0.04), 1.54 (95% CI 1.07-2.22; p = 0.02), and 1.41 (95% CI 1.16-1.72; p < 0.001), respectively. Corresponding results (model 2), comparing 4166 patients having low PA both baseline and at follow up with all other 11,296 patients were 1.68 (95% CI 1.41-2.01), 1.68 (95% CI 1.45-1.96), 2.12 (95% CI 1.48-3.03), and 2.03 (95% CI 1.66-2.48) (all p < 0.001) and compared to 2797 patients with low baseline PA and higher PA at follow up were 2.51 (95% CI 1.87-3.38), 2.54 (95% CI 1.98-3.27), 3.26 (95% CI 1.74-6.10), and 2.91 (95% CI 2.08-4.07) (all p < 0.001). CONCLUSIONS: This large observational study of patients with type-2 diabetes showed considerably increased risks for CVD and mortality with low PA. PMID- 24227184 TI - The impact of the macroeconomy on health insurance coverage: evidence from the Great Recession. AB - This paper investigates the impact of the macroeconomy on the health insurance coverage of Americans using panel data from the Survey of Income and Program Participation for 2004-2010, a period that includes the Great Recession of 2007 2009. We find that a one percentage point increase in the state unemployment rate is associated with a 1.67 percentage point (2.12%) reduction in the probability that men have health insurance; this effect is strongest among college-educated, white, and older (50-64 years old) men. For women and children, health insurance coverage is not significantly correlated with the unemployment rate, which may be the result of public health insurance acting as a social safety net. Compared with the previous recession, the health insurance coverage of men is more sensitive to the unemployment rate, which may be due to the nature of the Great Recession. PMID- 24227185 TI - Clinical psychology in medical settings: Psychology's role in health care. AB - The number of clinical psychologists working in medical settings has grown along with the range of services provided by psychologists to patients with a multitude of medical problems across the lifespan. Medical care cost savings brought about by these psychological interventions is highlighted along with issues of public policy and specialization of training. The opportunity for ongoing development of clinical psychology in medical settings is described as unlimited and the mission of the newJournal of Clinical Psychology in Medical Settings is presented as supporting that growth. PMID- 24227186 TI - Health and behavior: The coming together of science and practice in psychology and medicine after a century of benign neglect. AB - For thousands of years, physicians had available only a few drugs with which to minister to patients and the practice of psychology was an integral and therapeutically powerful component in the practice of medicine. Thus, good "bedside medicine" consisting of empathy, compassion, and a nurturant attitude toward the ill individual was a major component of the physician's armamentarium until relatively recently. However, the explosion in scientific knowledge in biology, physiology, chemistry, and microbiology which began a century ago and has continued through the twentieth century helped produce several generations of physician specialists and subspecialists with little knowledge of the powerful role psychological factors play in health and illness. As a result, practitioners of medicine and practitioners of psychology have had little or no contact during most of this century. However, as advances in microbiology, public health, and nutrition have eradicated many of the infectious diseases, infirmities associated with one's lifestyle have replaced the latter as the major causes of death today. One offshoot of this shift is that after a century of benign neglect, physicians and psychologists have rediscovered a common ground in the arena labeled health and behavior. Some factors responsible for these recent developments are highlighted. PMID- 24227188 TI - Psychological assessment of quality of life following liver transplantation. AB - Administered measures of functional status, psychological distress, and quality of life to a consecutive series of 48 liver transplant recipients in follow-up clinic. Results showed that nearly total functional recovery was the norm. Thirty six patients (75%) had a Karnofsky Performance Status (KPS) score of 80-100. Twelve transplant recipients had KPS scores below 80; none were employed, and most had been transplanted within 1 year. In spite of their impaired financial status, eight of these 12 reported being mostly satisfied on the self-report Quality-of-Life Scale (QLS). For the posttransplant sample as a whole, 83% were mostly satisfied with their quality of life. Pre- and posttransplant patient samples were not significantly different in reporting mild emotional distress. Results for the small subgroup with significant objective or subjective problems in achieving acceptable quality of life following liver transplantation were reviewed. Higher than normal emotional distress on the Symptom Checklist (SCL-90 R) was consistently reported by these patients. Prospective studies are needed to identify predictor variables of quality-of-life problems and to develop prevention and rehabilitation interventions. PMID- 24227189 TI - Relative absence of neuropsychological deficit in patients with low grade astrocytomas. AB - Given the current accuracy and precision of modern brain imaging technology, there is presumed to be little utility in neuropsychological assessment procedures in patients with brain tumors. The primary exposure of many clinical neuropsychologists to patients with brain tumors is during their training, in the form of didactic classroom activities, such as reviewing the brain tumor cases of early investigators in the field. Historically, these brain tumors were the more aggressive and destructive tumors, such as grade III and IV astrocytomas, that could be identified with pre CT and pre MRI technology. With current imaging technology, low grade tumors that might previously have gone undiagnosed for years can be detected and patients followed over time. This series of cases represents documentation of the very unique neuropsychological status of patients with relatively slow growing, infiltrative brain tumors classified as grade II astrocytomas. The potential relevance of neuropsychological assessment for such cases is discussed. PMID- 24227187 TI - Current status of psychological research in organ transplantation. AB - Research addressing the psychological concomitants of organ transplantation is reviewed. Specifically, cognitive, behavioral, and psychosocial correlates of kidney, heart, liver, and bone marrow transplantation in both children and adults are discussed. Despite several conceptual and methodological shortcomings of the psychologically-based research in this area, results seem to indicate that organ transplantation is associated with many psychological issues at pretransplantation, posttransplantation, and follow-up periods. Implications of these general findings for the advancing roles of the health psychologist in organ transplantation are discussed. PMID- 24227190 TI - Variation in tibial tubercle-trochlear groove measurement as a function of age, sex, size, and patellar instability. AB - BACKGROUND: The tibial tubercle-trochlear groove (TT-TG) measurement was developed to quantify morphologic abnormalities about the knee associated with patellar instability and to help guide surgical decision making. PURPOSE: To assess variations in TT-TG as a function of patient age and size in a population of patients with patellar instability compared with those with no instability. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: All patients younger than 20 years who underwent surgery for patellar instability from 2010 to 2012 were included in this retrospective study. A total of 180 patients with no history of patellar instability or patellofemoral complaints were used as a control group. The TT-TG was measured on magnetic resonance axial images using the centers of the tibial tubercle and the trochlear groove. Data were normalized based on patient height, weight, body mass index (BMI), and femur width. Alpha was set at P < .05 to declare significance. RESULTS: The average age of the 45 patellar instability patients was 15.4 years (range, 10-18 years), their mean TT TG was 16.3 mm (range, 6.5-26 mm), and 51% were male. By comparison, the mean age of the control group was 16 years (range, 10-19 years), the mean TT-TG was 11.7 mm (range, 3-22 mm), and 58% were male. The TT-TG and the normalized TT-TG for height, weight, BMI, and femur width were all greater in the patellar instability group compared with the control group (P <= .001). Thirty-one percent of patients had a TT-TG greater than 20 mm in the instability group compared with 3% in the control group (P < .05, specificity 97%, sensitivity 31%). The TT-TG was found to increase as a function of height in both groups (r = 0.14, P = .04) and decreased with age only in the instability group (r = -0.3, P = .04). CONCLUSION: An elevated TT-TG is associated with patellar instability both in pediatric and adolescent patients. However, this measurement varies as a function of patient age and height, with each centimeter in height increasing the TT-TG by 0.12. Normalization of TT-TG to patient height may control for size variations and should be undertaken in the work-up and management of patients with patellar instability. PMID- 24227192 TI - Woodstove emission measurement methods: Comparison and emission factors update. AB - On February 26, 1988, the U.S. Environmental Protection Agency promulgated Standards of Performance for residential wood heaters, or woodstoves. Over the past several years, a number of field studies have been undertaken to determine the actual level of emission reduction achieved by new technology woodstoves in everyday use. These studies have required the development and use of particulate and gaseous emission sampling equipment compatible with operation in private houses. Since woodstoves are tested for certification in the laboratory using EPA Methods 5G and 5H, it is of substantial interest to determine the correlation between these regulatory methods and the in-house equipment. Two in-house sampling systems have been used most widely. One is an intermittent, pump-driven particulate sampler which collects particulate and condensable organics on a filter and organic adsorbent resin. Oxygen concentration is measured by a sensor in the sample line. The sampler is controlled by a data logger which also records other parameters of interest. The second system uses an evacuated cylinder as the motive force. Particulate and condensable organics are collected in a condenser and dual filter. The sampler operates continuously whenever the stack temperature is above the set point. Average stack gas concentrations are measured from the evacuated cylinder at the conclusion of the sampling period. Both samplers were designed to operate unattended for 1-week periods. A large number of tests have been run comparing Methods 5G and 5H to both of the field samplers. This paper presents these comparison data and determines the relationships between laboratory certification sampling methods and field samplers. PMID- 24227193 TI - Comparison of PM10 concentrations in high- and medium-volume samplers in a desert environment. AB - The USEPA replaced TSP with PM10 as the National Ambient Air Quality Standard for particulate matter. The commercially available PM10 sampler is a high-volume model using quartz fiber filters. In certain investigations, such as source apportionment studies, chemical analysis of the filter is necessary, however, many analyses cannot be run on quartz filters. An alternate filter such as Teflon is amenable to XRF and ion chemical analyses but is not amenable to analysis for carbon. To overcome these problems DRI constructed a medium-volume PM10 sampler that is capable of collecting particulates on both Teflon and quartz fiber filters simultaneously. This paper describes the design of the DRI medium-volume PM10 sampler, discusses a method for determining equivalence of two samplers, the results of applying the method to test the equivalence of the medium-volume sampler and a commerical high-volume sampler, and examines differences between PM10 and TSP measurements in a southwestern desert. PMID- 24227191 TI - Angiogenic growth factors augment K-Cl cotransporter expression in erythroid cells via hypoxia-inducible factor-1alpha. AB - The potassium chloride cotransporters (KCC) family of proteins are widely expressed and are involved in the transepithelial movement of potassium and chloride ions and the regulation of cell volume. KCC activity is high in reticulocytes, and contributes to the dehydration of sickle red blood cells. Because plasma levels of both vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are elevated in sickle cell individuals, and VEGF has been shown to increase KCC expression in other cells, we hypothesized that VEGF and PlGF influence KCC expression in erythroid cells. Both VEGF and PlGF treatment of human erythroid K562 cells increased both mRNA and protein levels of KCC1, KCC3b, and KCC4. VEGF- and PlGF-mediated cellular signaling involved VEGF R1 and downstream effectors, specifically, PI-3 kinase, p38 MAP kinase, mTOR, NADPH-oxidase, JNK kinase, and HIF-1alpha. VEGF and PlGF-mediated transcription of KCC3b and KCC4 involved hypoxia response element (HRE) motifs in their promoters, as demonstrated by promoter analysis, EMSA and ChiP. These results were corroborated in vivo by adenoviral-mediated overexpression of PlGF in normal mice, which led to increased expression of mKCC3 and mKCC4 in erythroid precursors. Our studies show that VEGF and PlGF regulate transcription of KCC3b and KCC4 in erythroid cells via activation of HIF-1alpha, independent of hypoxia. These studies provide novel therapeutic targets for regulation of cell volume in RBC precursors, and thus, amelioration of dehydration in RBCs in sickle cell disease. PMID- 24227194 TI - Phytomonitoring of urban-industrial pollutants: A new approach. AB - Biological effect monitoring of urban-industrial pollutants was carried out using an 'air pollution tolerance index' (APTI) of plants. For the purpose four leaf parameters - namely, ascorbic acid, total chlorophyll, relative water content and leaf extract pH - were combined together in a formulation signifying the APTI of plants. The index indicated the plant response at the cell membrane and chloroplast levels. SitesP 1,P 2 andP 3 were selected in western parts of Varanasi, India, near the junction of a national highway and a railway track. The control site was selected in the University campus. In the prevailing wind direction from siteP 1, pollution zones I, II and III were marked. None of the four above mentioned plant parameters indicated a consistent response to pollutants. However, the APTI showed the most sensitive and consistent response of plants to urban-industrial pollutants. The APTI of plants showed a marked gradation as the pollutant load decreased from zone I, II and III to the control site. The APTI can be used as a good indicator of the impact of pollution on plants. PMID- 24227195 TI - Evaluation of acoustical particle counter for the sizing of fog droplets. AB - An acoustical particle counter (or acoustical particle sizing device) was evaluated for counting and sizing of fog droplets. Fog droplets were generated under controlled conditions in the laboratory. Fog droplet sizes were measured by an optical and an electron microscope and compared to results from the acoustical particle counter. Most of the droplets were found to be in the size range of 5-30 um. The mean diameters estimated from the acoustical particle counter were in agreement with the microscope values of mean droplet diameter. A Rich 100 condensation nuclei monitor was also operated simultaneously during the fog droplet counting to monitor the condensation nuclei counts in the laboratory. The results indicate that condensation nuclei count is inversely correlated with the fog droplet threshold diameter. Aerosols of uniform size (35 um) were generated by the vibrating orifice monodisperse aerosol generator and counted at three different flow rates by the acoustical particle counter. The counts/liter/minute were similar, indicating the reliability of the acoustical particle counter. PMID- 24227196 TI - Cleanup of fractured rock aquifers: Implications of matrix diffusion. AB - As contamination moves through a fractured rock aquifer, it tends to diffuse from the flowing fracture water into the rock's essentially stagnant pore water. This process tends both to retard a contamination plume's advance through a fractured rock aquifer and to substantially increase the difficulty of purging contamination from the aquifer. A mathematical model has been developed to evaluate the potential impact of this phenomenon upon water quality restoration in fractured rock aquifers. The numerical modeling reveals that cleanup of fractured rock aquifers will, in many cases, require many decades, even centuries, to achieve, particularly where substantial improvements in water quality are sought. The parameters which most strongly govern the degree to which matrix diffusion prolongs the aquifer restoration process are the rock's matrix porosity, fracture spacing, and matrix diffusivity, the chemical identity of the contaminant(s), and the length of time the aquifer has been contaminated.Since sedimentary rocks tend to have both relatively high matrix porosities and matrix diffusivities, it can be particularly difficult to purge contamination from sedimentary rock aquifers. Crystalline rocks, in contrast, typically have lower matrix porosities and matrix diffusivities, and therefore undergo more rapid cleanup. However, even in crystalline rocks, attainment of very high degrees of water quality improvement may be problematic. Numerical modeling also indicates that conventional groundwater 'pump and treat' programs are not likely to be very effective in speeding up aquifer restoration if the rate limiting step in the process is diffusion of contaminants from the rock matrix. PMID- 24227197 TI - Macrobenthic surveys as a valuable tool for assessing freshwater quality in the Iberian Peninsula. AB - Relationships between natural macrobenthic communities and aquatic environmental conditions have been recently used to perform the Biological Monitoring Water Quality (BMWQ) score system for assessing freshwater quality in the Iberian Peninsula. In this paper, the second version of the BMWQ score system is applied to two selected field studies (organic and nonorganic pollution) in order to illustrate the suitable functional character of this method. The total BMWQ (t BMWQ) score and the average BMWQ (a-BMWQ) score are calculated, and their relationships with diversity indices are also examined. The BMWQ method appears to be very sensitive to changes in freshwater quality generated by simple organic pollution, but this method appears to be less sensitive to changes generated by complex nonorganic pollution. In addition, both scores are more sensitive measures to assess macroinvertebrate response to organic pollution than total density and diversity indices, exhibiting higher positive coefficients of linear correlation with Camargo's diversity index than with Shannon's and MacArthur's diversity indices. However, the a-BMWQ score is more sensitive to changes in family composition than the t-BMWQ score, whereas this latter score is more sensitive to family richness and sample size. In this sense, the use of the a BMWQ score is recommended for the biological assessment of freshwater quality degradation in the Iberian Peninsula. More information is obtained for less effort when the a-BMWQ score is used. PMID- 24227198 TI - Erratum. PMID- 24227199 TI - DNA copy number aberrations in endobronchial lesions: a validated predictor for cancer. AB - We recently identified a DNA copy number aberration (CNA)-based classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia. The current study was set out to validate the prediction accuracy of this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions. The study included 36 high-risk subjects who had endobronchial lesions of various histological grades that were identified and biopsied by autofluorescence bronchoscopy and were subjected to arrayCGH in a nested case-control design. Of the 36 patients, 12 had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer free (78 months, range 21-142). The previously defined CNA-based classifier demonstrated 92% (95% CI 77% to 98%) accuracy for cancer (in situ) prediction. All nine subjects with CNA-based classifier-positive endobronchial lesions at baseline experienced cancer outcome, whereas all 24 controls and 3 cases were classified as being low risk. In conclusion, CNAs prove to be a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic intervention or surveillance. PMID- 24227200 TI - Protease-mediated ectodomain shedding. AB - Ectodomain shedding is the proteolytic cleavage of cell surface proteins resulting in the loss of the extracellular domains. This mechanism is important in a variety of normal and pathological processes, including growth factor signalling, cell adhesion, inflammation and cell survival. Elevated protease activity in the lungs is a key pathological mechanism in emphysema which could enhance ectodomain shedding in lung cells. Here, the major steps and consequences of ectodomain shedding are reviewed. PMID- 24227201 TI - 2-Naphthol-phosphatidylethanolamine: A fluorescent phospholipid analogue for excited-state proton transfer studies in membranes. AB - The fluorescence properties of the phospholipid derivative,N-[1-(2-naphthol)] phosphatidylethanolamine (NAPH-PE), have been studied by steady-state and time resolved fluorescence techniques. The new probe is a naphthol adduct of phosphatidylethanolamine. The emission spectrum of the fluorescent phospholipid depends on the pH and on the proton acceptor concentration as expected for a typical two-state excited-state proton transfer reaction. In ethanol solutions at an apparent pH of 6.7 and in the presence of acetate anion (0.14M), a biexponential decay is obtained from global analysis of the data. The lifetimes,tau 1=3.9 ns andtau 2=6.2 ns. are constant across the spectral region 350-460 nm. The decay-associated spectra and the species-associated spectra reproduce well the profiles reported for a two-state excited-state proton transfer reaction. The fluorescent phospholipid has been incorporated into dimyristoyllecithin and dipalmitoyllecithin vesicles. Although lower proton transfer is found, the reaction appears to be dependent on the gel-to-liquid crystalline phase transition of the lipid membrane. In addition, the steady-state anisotropy of NAPH-PE measured as a function of temperature trace the phase transition of the two vesicle systems. Thus, it is shown that the physical state of the bilayer affects a reaction which takes place at the membrane surface. In the presence of acetate ions (0.3M), global analysis, performed in terms of fluorescence decay parameters, recovers preexponential coefficients that are consistent with an excited-state proton transfer reaction. The short lifetime drops from 3.9 to 0.44 ns without significant changes of the longer-lifetime component. PMID- 24227202 TI - Three-photon excitation ofp-quaterphenyl with a mode-locked femtosecond Ti:sapphire laser. AB - We observed emission fromp-quaterphenyl (p-QT) at 360 nm when exposed to the focused light from a femtosecond (fs) Ti:sapphire laser at 850 nm. This wavelength is too long to allow two-photon excitation of p-QT. The emission intensity of p-QT was found to depend on the cube of the laser power at 850 nm, suggesting that excitation occurs due to a three-photon process. The same emission spectrum and single exponential decay times were observed for three photon excitation at 850 nm as for two-photon excitation at 586 nm and for one photon excitation at 283 nm. The same rotational correlation times were observed for one-, two-, and three-photon excitation, but higher time-zero anisotropies were observed for two- and three-photon excitation. The steady-state anisotropies for one-, two-, and three-photon excitation are precisely consistent with cos(2)theta, cos(4)theta, and cos(6)theta excitation photoselection, where theta is the angle between the electric field of the incident light and the absorption dipole. These experiments were performed with 3*10(-5) M solutions of p-QT. Use of such low concentrations was possible because p-QT displays one of the highest apparent cross sections we have observed to date for three-photon excitation. The spatial distribution of the excited fluorescence was less for three-photon excitation than for two-photon excitation of Coumarin 102 at the same 850-nm excitation wavelength. The high cross section, photostability, and clear cos(6)theta photoselection of p-QT make it an ideal three-photon standard for spectroscopy and microscopy. PMID- 24227203 TI - Spectral properties of the prototropic forms of fluorescein in aqueous solution. AB - The commonly used fluorescent probe, fluorescein, can exist in seven prototropic forms. We have used global analysis procedures to reanalyze the absorption data of Diehl and Horchak-Morris (Talanta 34, 739-741, 1987) in terms of five alternative ionization models. We identify the forms of fluorescein present in aqueous solution and the pK a of each ionisation transition. The pKa values of the neutral xanthene, carboxylic acid, and cationic xanthene groups are 6.3, 3.1 3.4, and 3.1-3.4, respectively, and the pKa value of lactonization is 2.4. As a consequence, the neutral form of fluorescein is a mixture of the lactone (70%), zwitterionic (15%), and quinoid (15%) forms. A knowledge of the forms present in solution permits the characterization of their spectral properties. It is shown that the quinoid and monoanion forms have similar absorption spectra, while the zwitterion spectrum is similar to that of the cation but blue-shifted by 3 nm. The emission spectra of the monoanion and quinoid forms are also identified and shown to be similar but not identical. A model for the excited-state reactions of fluorescein is presented. PMID- 24227204 TI - Time-resolved response of fluorescent alkali ion indicators and detection of short-lived intermediates upon binding to molecular cavities. AB - Stopped-flow kinetic studies have been performed to determine the kinetic parameters of K(+) binding to the fluorescent cryptand F222 and of Na(+)binding to F221 at pH 8.O. The results clearly indicate that a comparatively stable intermediate is formed before the rate-limiting binding step occurs with a rate constant around 30 s(-1) under the chosen experimental conditions. The conversion of the intermediate to the final cation complex is assigned to the final penetration of the already bound, but still partially solvated cation into the ligand's cavity. The main fluorescence intensity change found upon cation binding is attributed to the second reaction step, and not to the fast, initial binding reaction. The comparatively slow overall binding reaction is interpreted on the bases of a special solvate substitution mechanism which, in principle, can also account for the 1500 times slower binding of Ca 2(+) to F221. With regard to time resolved analytical Na(+) and K(+) determinations, the response times under the chosen conditions are around 20 ms. Differentiation between Na(+) and Ca(2+), for example, is possible with F221 on the basis of completely different response times. PMID- 24227205 TI - Conformational changes of Na,K-ATPase probed with eosin Y. AB - Time-resolved fluorescence and binding studies have been carried out on Na,K ATPase in the presence of the fluorescent dye eosin Y to obtain thermodynamic and kinetic parameters for the interaction of the enzyme with different cations. Eosin Y binding is indicated by a 3 ns fluorescence decay process and is observed only in the presence of mono- and divalent cations. This type of cation binding is interpreted as a nonselective electrostatic interaction, with negatively charged groups of the enzyme providing a high-affinity eosin Y binding site. Eosin Y binding is observed only under conditions where the enzyme exists in the conformational state F1. The kinetic parameters of eosin Y binding have been determined employing stopped-flow fluorometry. PMID- 24227206 TI - Time-resolved fluorescence studies of ribonuclease T1 in reversed micelles. AB - Time-resolved fluorescence intensity and anisotropy decay data were obtained for ribonuclease T1 entrapped in bis(2-ethylhexyl) sodium sulfosuccinate/heptane reverse micelles, as a function of the size of the inner water pool at neutral pH. Data have been presented previously to show that this protein retains its native structure and undergoes reversible thermal unfolding in these reverse micelles (Shastry and Eftink,Biochemistry 36, in press). The fluorescence decay of entrapped protein is similar to that for the protein in buffer. The rotational correlation time of entrapped ribonuclease T1 is found to be longer than that in buffer; this rotational correlation time decreases with increasing size of the water pool but is still over twice the value for the protein in buffer for the largest size of water pool investigated, indicating an increased microviscosity within the reverse micelle. Thermal unfolding of the protein results in a significant decrease in the rotational correlation time of the entrapped proteins, consistent with the protein being unfolded but not interacting with the inner surfactant wall of the reverse micelle. PMID- 24227207 TI - Resolution of multiexponential spectral relaxation of Yt-base by global analysis of collisionally quenched samples. AB - We measured the wavelength-dependent intensity decays of 4,9-dihydro-4,6-dimethyl 9-oxo-1H-imidazo-1,2a-purine (Yt-base) in propanol to determine the time-resolved emission spectra and rates of spectral relaxation. We found that resolution of the spectral relaxation times was dramatically improved by global analysis of the frequency-domain data with increasing amounts of the collisional quencher CCl4. Collisional quenching preferentially decreases the longer-lived relaxed component of the emission, thereby increasing the fractional contribution of the incompletely relaxed portion of the emission. The data could not be explained by a single spectral relaxation time, and at least two relaxation times are needed to describe the time-dependent emission center of gravity of Yt-base. PMID- 24227208 TI - Arterial ischemic stroke as a complication to disseminated infection with Fusobacterium necrophorum. AB - Lemierre syndrome (LS) is a rare complication of oropharyngeal and odontogenic infections in otherwise healthy young individuals. It is characterized by septic internal jugular vein thrombophlebitis and disseminated metastatic abscesses. Cerebral arterial ischemic stroke is rarely seen in LS. The authors present a 14 year-old, previously healthy girl, who developed cerebral arterial infarction following acute tonsillitis and abscess formations due to Fusobacterium necrophorum. PMID- 24227209 TI - Phenylpropenoid phenolics in sweetbay magnolia as chemical determinants of host use in saturniid silkmoths (Callosamia). AB - Host plant chemistry can play an important role in determining the evolution of host use patterns in herbivorous insects by influencing host selection, consumption, and assimilation of foliage. We used a comparative approach to test the hypothesis that specialist herbivores of sweetbay magnolia (Magnolia virginiana) possess adaptations that allow them to overcome chemical deterrents or toxins that prevent herbivory by unadapted herbivores. The three silkmoth species in the genusCallosamia can be collectively regarded as specialists on magnoliaceous hosts; however, only the monophagousC. securifera is able to complete development on sweetbay magnolia, its natural host. In laboratory assays with intact foliage, bothC. angulifera and the polyphagousC. promethea fed readily on sweetbay but were unable to survive past the third instar. Two neolignan compounds, magnolol and a biphenyl ether, were found to reduce neonate growth and survival of unadapted herbivore species when painted on acceptable host leaves at concentrations similar to those found in sweetbay foliage. Both compounds significantly reduced neonate growth ofC. angulifera andC. promethea but had no effect on the sweetbay specialist,C. securifera, indicating that the latter species possesses the unique ability in the genus to tolerate, metabolize, or otherwise circumvent the phytochemical defenses of this host. PMID- 24227210 TI - Disruption of male oriental fruit moth to calling females in a wind tunnel by different concentrations of synthetic pheromone. AB - Disruption of male Oriental fruit moth orientation to calling females was studied in a wind tunnel by surrounding calling female moths with septa loaded with synthetic pheromone. At the lowest loadings, 0.01 and 0.1ug, which produced release rates well below those of calling females, some males flew to septa instead of the females. At loadings of 1 and 10ug, which produced release rates close to those of a calling female, more than half the males flew to septa instead of the females, but there was little evidence of habituation at any of these loadings. At higher loadings, 100 and 1000ug, upwind flight of males was arrested, and many males remained inactive, indicating habituation. Preexposure of the males for 3 hr to ambient pheromone concentrations in the tunnel had no significant effect on numbers of disrupted males. However, at the 1000-ug loading, most of the males that had been preexposed to the synthetic pheromone remained inactive. This may indicate a higher level of habituation than among males that had not been preexposed, most of which flew, although they subsequently showed flight arrestment. Levels of disruption were similar to those found for the spruce budworm in comparable experiments. In both species, less than 1% of the males were able to locate females when time-averaged concentrations of synthetic pheromone were above 20 ng/m(3). However, levels of inactivity and flight arrestment were higher among male Oriental fruit moths than among male spruce budworms, which may explain why Oriental fruit moths are more susceptible to disruption than are spruce budworms. PMID- 24227211 TI - The role of primary and secondary metabolites in chrysanthemum resistance toFrankliniella occidentalis. AB - The presence of deleterious secondary metabolites to western flower thrips (WFT) (Frankliniella occidentalis Pergande) in several chrysanthemum (Dendranthema grandiflora Tzvelev) cultivars was tested. WFT performance on leaf sap mixed with artificial diet was compared to WFT performance on a control of artificial diet mixed with water. Leaf sap of six of 10 chrysanthemum cultivars tested had a significant negative effect on WFT performance and therefore contained deleterious secondary metabolites. Leaf sap of a resistant and a susceptible chrysanthemum cultivar were fractionated by gel to study the role of secondary metabolites in greater detail. None of the 20 individual fractions obtained had a negative effect on WFT performance, whereas after mixing of these fractions activity was found again. Moreover, WFT performance on the fraction mixture of the resistant cultivar was significantly lower than on the susceptible fraction mixture. The results suggest that WFT resistance in the cultivars studied was caused by several secondary metabolites that had an additional or synergistic negative effect on WFT performance. The role of a deficiency of primary metabolites in WFT resistance of chrysanthemum was also investigated. WFT performance on leaf sap with and without extra primary metabolites (artificial diet) was compared. The variance in WFT performance was significantly smaller when extra primary metabolites were added; WFT performance on leaf sap with and without extra primary metabolites was not correlated. The results suggest that resistance was partly caused by a deficiency of primary metabolites. PMID- 24227212 TI - Scarab beetleAnomala albopilosa albopilosa utilizes a more complex sex pheromone system than a similar speciesA. cuprea. AB - Four compounds have been identified as sex pheromone constituents of the scarab beetleAnomala albopilosa albopilosa, namely (R, Z)-5-(-)-(oct-1 enyl)oxacyclopentan-2-one (buibuilactone), 2-(E)-nonenol, 2-(E)-nonenal, and methyl benzoate (in the ratio 10:3:3:1). The diel rhythm of pheromone release inA. a. albopilosa showed a peak at the beginning of the scotophase, which is also a peak of mating activity. On the other hand, the similar speciesA. cuprea utilizes a two-constituent sex pheromone, having a common major component, but the pheromone is released both during scoto-and photophase. Temporal difference in mating activity and pheromone release along with chemical diversity seem to form the basis for maintaining species specificity in pheromonal communication betweenA. a. albopilosa andA. cuprea. PMID- 24227213 TI - Food deprivation affects preference of sheep for foods varying in nutrients and a toxin. AB - We investigated how food deprivation affected preference of lambs for foods that varied in concentrations of nutrients and a toxin. Thirty lambs (10 lambs/treatment) were fed different amounts of alfalfa pellets (high in protein, marginal in energy for growth) as a basal ration (20, 40, or 60 g/kg body weight). Every morning, prior to ingesting the basal ration of alfalfa pellets, each lamb was offerend three foods for 15 min. The foods contained different amounts of energy and a toxin, depending on the addition of barley (energy) and LiCl (toxin) to alfalfa. The proportions of barley and LiCl changed every five days during the 25-day study. The results showed: (1) all lambs preferred food that was high > intermediate > low in energy (barley) in the absence of LiCl, but all lambs decreased consumption of foods high in energy as LiCl concentrations increased; (2) the greater the level of food deprivation, the lower the consumption of foods containing LiCl, even if the foods provided high levels of energy; (3) lambs moderately food deprived or fed ad libitum ingested more LiCl than lambs that were highly deprived; and (4) lambs quickly (15 min/day) regulated intake of foods in response to changes in barley and LiCl concentrations. Thus, our results suggest that the interaction between nutritional status and toxicosis plays an important role in food preference of lambs. Our findings also suggest that toxic plants may kill herbivores that lack nutritious alternative foods not only because the animals are forced to be less discriminating, but also because they are more susceptible to toxins. PMID- 24227214 TI - Variation of total phenolic content and individual low-molecular-weight phenolics in foliage of mountain birch trees (Betula pubescens ssp.tortuosa). AB - We studied seasonal and between-tree variation in the composition and content of total and individual low-molecular-weight phenolics (LMWP) in leaves of mountain birch trees (Betula pubescens ssp.tortuosa). The major phenolic compounds were chlorogenic acid, quercetin-3-O-beta-D-glucuronopyranoside, myricetin-3-O-(5 acetyl)-L-rhamnopyranoside, and 1-O-galloyl-beta-D-(2-O-acetyl)-glucopyranose. The content of total phenolics, as well as the sum of individual LMWP, varied only slightly among trees while variation in contents of individual LMWP was large. Concentrations of almost all phenolics decreased during the growing season but pairwise correlations between individual phenolics remained similar over the whole season indicating tree-specific LMWP profiles over the season. Among flavonoids, the between-tree component of variation was 2.6 times as large as the seasonal component, while for variation of nonflavonoids the between-tree component was larger than the seasonal one. To explain the significant correlations within both flavonoid and nonflavonoid compounds, we discuss the biogenesis of LMWP in birch leaves, as well as their ecological role. PMID- 24227215 TI - Antifouling activity oflyso-platelet-activating factor extracted from australian spongeCrella incrustans. AB - Larvae of the ascidianClavelina moluccensis do not settle in the field on the spongeCrella incrustans and are deterred from settling by crude chemical extracts of the sponge. Progressive refinement of extracts, guided by bioassays, led to the identification oflyso-platelet-activating factor (lyso-PAF) from the sponge.lyso-PAF is inhibitory in assays using ascidian, bryozoan, barnacle, and algal settlement and mussel byssal attachment. Its role in the field has not yet been demonstrated. PMID- 24227216 TI - Sex recognition inDiglyphus isaea walker (Hymenoptera: Eulophidae): Role of an uncommon family of behaviorally active compounds. AB - The sexual behavior of the ectoparasitoidDiglyphus isaea is described. Recognition of the female by the male occurs at close range. Males initiate courtship behavior in the presence of a living female regardless of age, as well as in the presence of a female killed by freezing. Courtship behavior is not observed in the presence of a dead female washed with organic solvents but could be elicited using a lure covered with a female organic extract. These findings demonstrate that each sex develops a specific chemical signature that can be dissolved in hexane and transferred to a lure. Analysis of organic extracts by gas chromatography revealed chemical dimorphism between the two sexes. Gas chromatography coupled with mass spectrometry showed that the main components in females were esters of medium-chain fatty acids and long-chain 11-alcohols. There were few hydrocarbons. Female esters, which were present in only small proportions in males, were recovered in the nonhydrocarbon fraction obtained after fractionation of the total extract on a silica-filled microcolumn as a mixture containing 11-heneicosyl, 11-docosyl, 11-tricosyl, 11-tetracosyl, and 11 pentacosyl octanoate, and 11-docosyl, 11-tricosyl, 11-tetracosyl, and 11 pentacosyl decanoate. These results demonstrate that there is a specific gender related chemical signature. PMID- 24227217 TI - Hydrocarbons ofNasutitermes acajutlae and comparison of methodologies for sampling cuticular hydrocarbons of caribbean termites for taxonomic and ecological studies. AB - Using data from the arboreal nestingNasutitermes acajutlae (Holmgren), we propose standard collection and extraction methodology for characterization of cuticular hydrocarbons of termites under field conditions in the tropics. Specifically, we evaluated: (1) the effect of the duration and the number of extractions; (2) the effect of drying termites before extraction; (3) the effect of sample size; (4) the effect of solvents (ethanol versus hexane) on cuticular hydrocarbon profiles. Olefins comprise ca. 70% of the cuticular hydrocarbons ofN. acajutlae. Hydrocarbons consist of two distinct groups: early-eluting components, primarilyn alkanes and methyl-branched alkanes, and late-eluting compounds, which consist almost exclusively of unsaturated components with one to six double bonds. Soldiers have more early-eluting compounds than workers or alates. Nests from the same island had qualitatively similar, but quantitatively dissimilar hydrocarbon mixtures. Brief extractions of 300 live workers in 10 ml of hexane for only 20 sec produced a hydrocarbon mixture equivalent to a 10-min extraction. Long-term extraction of 300 workers in hexane for two years resulted in different mixtures of hydrocarbons. Drying workers tended to enhance extraction of the less abundant unsaturated compounds such as C41.4 and C41.5. A single extraction of a minimum of 100 workers (live or dried), with hexane for 20 sec to 10 min is best; these extraction regimes resulted in mixtures of hydrocarbons that are quantitatively very similar. For quantitative comparisons, extracts from dried samples should not be compared to those from live samples. Storage in ethanol caused numerous unidentified, nonhydrocarbon compounds to be extracted either from the cuticle or from internal tissues. PMID- 24227218 TI - Self-germination inhibitors fromColletotrichum fragariae. AB - The conidial germination ofColletotrichum fragariae in water was dependent on population, size germination was inhibited at higher concentrations of conidia in water. The inhibition was considered to be caused by some germination-inhibiting substances exuded from conidia, since the germination did occur after washing the conidia repeatedly. The germination-inhibiting substances were searched for in the acetone extract of potato-sucrose-agar (PSA) cultures of the fungus and five active compounds were isolated. Their structures were characterized spectroscopically. HPLC analysis indicated that one of the isolated compounds among these was exuded not only from mycelia but also from the conidia in water under crowded conditions. We suggest that these compounds control the conidial germination of the fungi. PMID- 24227219 TI - A comparison of the effectiveness of predator odor and plant antifeedant in deterring small mammal feeding damage on lodgepole pine seedlings. AB - The influence of mustelid (weasel) anal-gland compounds (semiochemicals) and a plant antifeedant (pinosylvin) on snowshoe hare (Lepus americanus) and meadow vole (Microtus pennsylvanicus) feeding damage was investigated. This study has shown conclusively that when applied to spring-planted lodgepole pine seedlings, pinosylvin is effective in significantly reducing feeding damage. Seedlings treated with pinosylvin suffered damage levels of 2.3% and 21.2% compared to the controls with damage levels of 24.5% and 41.0%. Weasel scent was found to reduce damage levels, but the reduction was not statistically significant in all blocks. PMID- 24227220 TI - Temporal clumping of bark beetle arrival at pheromone traps: Modeling anemotaxis in chaotic plumes. AB - The sequence of arrival of the bark beetlesIps typographus andPityogenes chalcographus (Coleoptera: Scolytidae) at traps baited with their synthetic pheromones was monitored with a portable fraction collector. Histograms of the natural arrival patterns of both species were nonrandom and clumped at shorter time scales (1-, 2-, 4-, 5-, or 6-min cells) but appeared random at larger time scales (10, 20 or 30 min). Monte Carlo generation of similar histograms showed them to be random at all of these time scales. A stochastic computer model could graphically simulate insect orientation to odor sources based on present theories of odor-modulated anemotaxis and casting. Although this model was used throughout, since it assumes only that insects cast perpendicular to the current wind direction, a second model could slightly improve orientation success. However, the second model requires that the insect remember its ground path (upwind) prior to losing the plume (after an abrupt wind direction change). The effects of casting and flight parameters on orientation success and randomness of arrival sequence within various plumes were determined by simulation. Similarly, the effects of random walks in plume direction, plume width, and wind speed were explored. The results showed that dynamic random variations in plume direction and especially wind speed could cause an otherwise random arrival sequence (e.g., under constant wind) to become clumped and nonrandom. Therefore, the clumped arrival patterns of bark beetles and other insects, includingSpodoptera litura, at pheromone sources could result from random-walk fluctuations in wind speed and wind direction. PMID- 24227221 TI - Enantiospecific pheromone production and response profiles for populations of pine engraver,Ips pini (Say) (Coleoptera: Scolytidae), in British Columbia. AB - Analyses of the enantiomeric composition of ipsdienol produced by individual male pine engravers,Ips pini (Say), from six populations in British Columbia, support the hypothesis that New York and Idaho races of this species hybridize in southeastern British Columbia. Production profiles, expressed as frequency distributions of (+):(-) ipsdienol ratios [= ratio of (S)-(+)-ipsdienol to (R)-( )-ipsdienol], were bimodal for four western British Columbia populations. The (+):(-) ratios ranged from 63:37 to 71:29. consistent with those previously found for the New York race. The profile for a southeastern population from Radium, British Columbia, was intermediate between those for the four western British Columbia populations and that from one population in Kimberley, British Columbia, just south of Radium. Males in the Kimberley population produce predominantly (R) (-)-ipsdienol, typical of California nad Idaho males. Response profiles of different individuals ofI. pini, determined by captures of beetles in multiple funnel traps baited with ipsdienol of 11 different (+):(-) ratios, were not consistent with production profiles. Populations in Williams Lake and Princeton, in western British Columbia, and Radium, in southeastern British Columbia, had response profiles with maximal attraction to ipsdienol over a broad range of (+):(-) ratios, falling off as enantiomeric purity was approached at either end of the spectrum. This type of response profile is consistent with that for the New York race, which has been shown to respond optimally to (+):(-) ratios ranging from 40:60 to 70:30. The response profile of the Kimberley population gradually declined from maximal attraction to ipsdienol with a (+):(-) ratio of 2:98 to the lowest response at a (+):(-) ratio of 98:2. The attraction ofI. pini to chemical stimuli in California is interrupted by ipsdienol with a (+):(-) ratio >5:95, a pheromone of a host competitor, the California five-spined ips,Ips paraconfusus Lanier. We hypothesie that the Idaho race, which does not compete withI. paraconfusus due to geographical separation, is characterized by a Kimberley-type enantiomeric response profile, intermediate between those of the New York and California races. PMID- 24227222 TI - Determination of fusaric acid in maize using molecularly imprinted SPE clean-up. AB - A new LC method to detect fusaric acid (FA) in maize is reported based on a molecularly imprinted SPE clean-up using mimic-templated molecularly imprinted polymers. Picolinic acid was used as a toxin analog for imprinting polymers during a thermolytic synthesis. Both acidic and basic functional monomers were predicted to have favorable binding interactions by MP2 ab initio calculations. Imprinted polymers synthesized with methacrylic acid or 2-dimethylaminoethyl methacrylate exhibited imprinting effects in SPE analysis. FA levels were determined using RP ion-pairing chromatography with diode-array UV detection and tetrabutylammonium hydrogen sulfate in the mobile phase. A method was developed to detect FA in maize using molecularly imprinted SPE analysis within the range of 1-100 MUg/g with recoveries between 83.9 and 92.1%. PMID- 24227223 TI - Role of the unfolded protein response in organ physiology: lessons from mouse models. AB - The endoplasmic reticulum (ER) is a key subcellular compartment involved in the folding and maturation of around one-third of the total proteome. Accumulation of misfolded proteins in the ER lumen engages a signal transduction pathway known as unfolded protein response (UPR) that feedback to recover ER homeostasis or to trigger apoptosis of irreversible damaged cells. The UPR is initiated by three main stress sensors including protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein 1alpha (IRE1alpha), which reprogram the genome through the control of downstream transcription factors. In this article, the authors have reviewed most relevant studies uncovering the physiological function of the UPR in different organs and tissues based on the phenotypes observed after genetic manipulation of the pathway in vivo. Biomedical applications of targeting the UPR on a disease context are also discussed. PMID- 24227224 TI - Physiological effects of hydrocarbons on the marine diatomCyclotella cryptica. AB - Effects of hydrocarbons on the marine diatomCyclotella cryptica have been studied in laboratory experiments. Low hydrocarbon concentrations (100 MUg. l(-1)) stimulate growth whereas higher concentrations (l mg. l(-1)) inhibit growth. The aromatics are most toxic among the hydrocarbons, whereas the paraffins do not seem to have any serious effect on growth or photosynthesis of the algae. Both aromatic and paraffin fractions affected the chlorophyll a, protein, and sugar contents of the cells. Toxicity levels were affected by the presence of dissolved organic material in the medium. Studies on the ultrastructure ofC. cryptica have shown that paraffins affect the thickness of the cell wall. PMID- 24227225 TI - Effect of light intensity on macromolecular synthesis in cyanobacteria. AB - The light-dependent incorporation of NaH(14)CO3 into low molecular weight compounds, polysaccharide, or protein was determined in cultures of the cyanobacteriumMerismopedia tenuissima incubated at a series of light intensities. There was an inverse relationship between incorporation into polysaccharide and protein. At light intensities of 90 MUE/m(2)/sec or above, relative incorporation of radioisotope into polysaccharide was greatest and relative incorporation into protein was lowest. Optimal relative protein accumulation occurred in samples incubated at 20 MUE/m(2)/sec. A broader optimum of light intensity for maximal protein accumulation was found if ammonia rather than nitrate was the nitrogen source. Physiological adaptation of cultures to growth at a particular light intensity did not alter the pattern of macromolecular incorporation when those cultures were tested over the series of light intensities. The response of cultures ofOscillatoria rubescens to light intensity was similar to that ofM. tenuissima, although incorporation into low molecular weight compounds was significantly greater.The effect of light intensity on macromolecular synthesis in a natural population ofOscillatoria rubescens was also determined. A pattern similar to that observed in batch cultures ofO. rubescens was occasionally found, but in other experiments there was no increase in relative protein incorporation when light intensity was decreased. PMID- 24227226 TI - Response of thermal algal-bacterial mat to grazing by brine flies. AB - Gelatinous mats of blue-green algae (cyanobacteria) and bacteria in alkaline thermal springs of Yellowstone National Park add biomass at the surface more rapidly than material is degraded in the anaerobic layers underneath. This inequality leads to flow diversion and exposure of mat surface. The microenvironment of these cool exposed "islands" is drastically altered as adults and larvae of ephydrid fly species invade, feed on, and solubilize the mat. We studied the effect of this grazing by comparing hot and cool ungrazed controls with mat that was cooled and remained open to invasion by ephydrid flies. Mat community biomass changes (ash free dry weight-AFDW) and changes in bacterial numbers were determined. Mat biomass was essentially unchanged for 3 weeks in the controls. Numbers of bacteria remained unchanged in the cool ungrazed control but decreased by more than 90% in the hot-ungrazed control. Grazing by ephydrid flies initially increased both mat biomass and numbers of unicellular heterotrophic bacteria. When grazed mat was reexposed to flowing hot water, biomass and bacterial numbers per mg AFDW declined immediately and significantly. The long term effect of grazing on the mat is solubilization with downstream biomass export and subsequent initiation of successional algal-bacterial mat regrowth. Our experimental results suggest an initial stimulation of net photosynthesis by grazing, possibly related to the promotion of bacterial activity resulting in the release of essential mineral nutrients and/or free CO2. PMID- 24227227 TI - Microbial succession on a chitinous substrate in a woodland stream. AB - Plate counts, scanning electron microscopy, and direct observations were utilized to determine successional trends of different groups of microorganisms onProcambarus versutus (Hagen) exoskeletons incubatedin situ in a second-order, acidic woodland stream in Northwest Florida. Plate counts and SEM observations indicated a definite successional pattern dominated in numbers initially by the nonbranching bacteria, followed by the actinomycetes. The greatest number of fungal propagules coincided with the least number of bacterial colony-forming units. Chitinoclastic bacterial colonizers increased on the substrate throughout the study, comprising as much as 88% of the total bacterial community during the final stages of chitin decomposition. Scanning electron micrographs taken over the duration of the study revealed the abundance of an actinomycete, identified as a species ofStreptomyces, on the exoskeleton. Enumeration of microorganisms in the stream sediment was also performed in conjunction with the exoskeleton analysis. Relatively constant numbers of bacteria and fungi were observed, with chitinoclastic bacteria comprising between 3 and 11% of the total sediment bacterial community. PMID- 24227228 TI - Measurement of in situ rates of nitrification in sediment. AB - A method has been developed for the measurement of nitrification rates in intact sediment cores without disturbing the concentration gradients of oxygen and ammonium. N-serve (2-chloro-6-trichloromethyl-pyridine), a specific inhibitor of the autotrophic ammonium oxidation, was injected into a 0-2 cm surface layer of the sediment (20 ppm) and added to the water column of sediment cores (5 ppm). N serve in these concentrations was sufficient to inhibit nitrification, but did not change the rate of ammonium production or incorporation in sediment suspensions, which were incubated aerobically and anaerobically. The ammonium accumulation in cores injected with N-serve was thus equal to the amount of ammonium which was oxidized to nitrate in the control cores. Nitrification rates were in the range of 0-3 mmol N m(-2) (-1.) PMID- 24227229 TI - Effects of temperature, ph, salinity, and inorganic nitrogen on the rate of ammonium oxidation by nitrifiers isolated from wetland environments. AB - Ammonium-oxidizing bacteria were examined in two wetland environments, a freshwater marsh and an estuarine bay, during a 2-year period. Two predominant types were consistently isolated, one from each environment. Both isolates were identified as species ofNitrosomonas. Using a closed culture, high cell density assay, the effects of temperature, pH, salinity, Na(+), K(+), nitrite, nitrate, and ammonium concentrations on ammonium oxidation were determined. Maximum activity was observed for the freshwater isolate at 35 degrees C, pH 8.5, salinities of 0.3 to 0.5% Na(+) and K(+), and ammonium concentrations greater than 0.5 g/l. For the estuarine isolate, maximum activity was observed at 40 degrees C, pH 8.0, salinities of 0.5 to 1.0%, 1.0% Na(+) and K(+), and 0.2 g/l ammonium. The estuarine isolate had a Na(+) requirement which could be partially substituted by the K(+), suggesting that the organism is a true estuarine bacterium. Nitrite inhibited both isolates at concentrations greater than 5 mg/l, whereas nitrate had no significant effect on either isolate. PMID- 24227230 TI - N2 Fixation (C2H 2 reduction) by epiphylls on coffee,Coffea arabica. AB - Nitrogen fixation (C2H2 reduction) by epiphylls on coffee,Coffea arabica, grown in sites with different degrees of shade, was determined. Coffee leaves with nitrogen-fixing epiphylls were found in all sites in approximately equal numbers. Rates of C2H2 reduction were similar for all sites and throughout the year, averaging 3.21 nmoles C2H2 reduced leaf with epiphylls(-1) day(-1). Apparently, neither rates of activity nor abundance of leaves with nitrogen-fixing epiphylls is related to the degree of shade in a site. No correlation was found between percent epiphyll cover and the presence or magnitude of nitrogen-fixing activity. Calculated annual fixation by epiphylls on coffee was low, ranging from 0.7 g N2 ha(-1) year(-1) for the shadeless site to 1.4 g N2 ha(-1) year(-1) for the site withIngajinicuil shade trees. These results suggest that epiphyll fixation is not an important source of nitrogen for the coffee ecosystem studied. PMID- 24227231 TI - Effect of Kepone on estuarine microbial activity. AB - In situ heterotrophic uptake of mixed(14)C-amino acids and direct viable cell (DVC) count of Chesapeake Bay water samples were not significantly affected by the insecticide Kepone at concentrations [Symbol: see text]0.01 mg/1. Maximum inhibition of heterotrophic uptake,ca. 85-90%, and DVC count, 45-97%, was evident at concentrations of Kepone exceeding 0.2 mg/1. A specific activity index (Metabolic Activity/DVC or Kepone-resistant DVC), heterotrophic uptake, and DVC count were found to be statistically correlated (a=0.05) to one another, but negatively correlated with concentration of Kepone. The direct viable cell count proved to be a rapid, simple method for estimating the effect of Kepone on in situ estuarine microbial activity. PMID- 24227233 TI - Mutants for rice storage proteins : 2. Isolation and characterization of protein bodies from rice mutants. AB - Rice storage proteins of the endosperm are localized in two types of protein bodies, PB-I and PB-II. Protein bodies were isolated by sucrose density gradient centrifugation from developing endosperm of three rice mutants, CM 21, CM 1675 and CM 1834, and characterized after pepsin-digestion treatment by protein contents determination. Mutant protein bodies (PBs) except for their internal structure, were similar in shape and density to PB-I of the variety Kinmaze. Electrophoretic analysis of PB-I polypeptides revealed that SDS (Sodium dodecylsulfate) bands of 13 and 16 kilodaltons consisted, respectively, of four and two individual polypeptides with different pI values, while the 10-kilodalton band behaved as a single polypeptide after isoelectric focussing (IEF) electrophoresis. The differences in the polypeptide composition induced by mutants were due to the decrease and/or increase in the content of specific PB-I polypeptides. Electron microscopic observations revealed that the typical lamellar structure of the PB-I is not visible in CM 1675. On the contrary, the inner portion of PB-I in CM 1834 and CM 21 showed higher electron density than that of the variety Kinmaze. On these two mutants, the content of pepsin indigestible and -digestible proteins were similar to those of Kinmaze, although the values of the PB-II/PB-I ratio were greater than those for Kinmaze, suggesting that these two mutants are high-glutelin rice mutants. PMID- 24227234 TI - Species relationships in the Hordeum murinum aggregate viewed from chloroplast DNA restriction fragment patterns. AB - Three annual widespread species of Hordeum were investigated by the fragment pattern method on their chloroplast (cp) DNA. The species were H. glaucum, H. leporinum and H. murinum; H. vulgare was surveyed for comparison. Twelve restriction enzymes were used, nine recognizing 6 bp, one 5 bp and two 4 bp, thus, randomly surveyed, a total of 2,113 bp or 1.6% of the cp genome. Differences in patterns were found in three enzymes, HindIII, CfoI and MspI. CfoI characterizes H. glaucum from the other two species. HindIII and MspI revealed polymorphisms within species. These results confirm previous numerical taxonomic relationships among these three closely related species. Furthermore, cpDNA polymorphism in Hordeum is discussed in view of earlier reports on cpDNA polymorphism in H. vulgare. The taxonomic implications of cpDNA polymorphism are discussed after reviewing several articles using the fragment pattern method on cpDNA. The importance of using material from several populations representative of a species is stressed. PMID- 24227235 TI - A note on the formation of optimal composite populations. AB - Two recently proposed methods for predicting the optimal breed contributions to a new composite breed are discussed. It is shown that these can both lead to incorrect solutions, and a reliable method is proposed. PMID- 24227236 TI - An investigation into the role of 5-Azacytidine in tissue culture. AB - A major problem associated with cereal biotechnology remains the extreme difficulty of reliably and efficiently regenerating plants from protoplasts. Because of the assumed inverse correlation between levels of the modified nucleotide 5-methylcytosine in a gene and the degree of transcription, we report here on experiments to determine whether exposure of maize and tobacco cultures to the 5-methylcytosine analogue 5-Azacytidine (5-Azt) induces gene de methylation and, as such, enhances tissue culture response, for example by increasing protoplast division frequency. The results show that whilst 5-Azt may be of use in expanding leaf areas capable of producing callus as well as increasing the amount of callus produced, in all other aspects 5-Azt is strongly inhibitory to growth at all but the lowest concentrations. Molecular analysis shows that no readily discernible changes in gene methylation status can be found, regardless of 5-Azt concentration or the gene probe used. Differences can, however, be found in methylation status between callus and developmentally determined tissues, irrespective of 5-Azt treatment. The results suggest that, apart from a very limited role, 5-Azt has no obvious use in tissue culture. PMID- 24227237 TI - Occurrence of 2n pollen and ps gene frequencies in cultivated groups and their related wild species in tuber-bearing Solanums. AB - The gene frequency for parallel spindles (ps) was estimated from the frequency of plants producing 2n pollen in three cultivated groups: 2x Phureja (phu), 2x Stenotomum (stn), and 4x Andigena (adg), as well as in four related wild taxa: 2x Solanum brevicaule (brc), 2x S. sparsipilum (spl), 4x S. gourlayi (grl) and 4x S. gourlayi-S. infundibuliforme hybrids (grl-ifd). Plants with more than 1% large pollen were considered as 2n pollen producers. Observations of meiosis in a sample of 2n pollen-producing plants indicated that parallel spindles is the mechanism of 2n pollen formation. The number of plants with 2n pollen among the total examined was 228 plants (15.5%) of 1,473 in 2x spl, 31 (26.7%) of 116 in 2x brc, 92 (17.4%) of 528 in 2x stn, 665 (22.1%) of 3,008 in 2x phu, 731 (51.4%) of 1,421 in 4x adg, 591 (41.2%) of 1,436 in 4x grl, and 36 (64.3%) out of 56 in 4x grl-ifd. The ps gene frequencies assuming Hardy-Weinberg equilibrium were: 0.393 for 2x spl, 0.462 for 2x brc, 0.417 for 2x stn, 0.470 for 2x phu, 0.847 for 4x adg, 0.801 for 4x grl, and 0.895 for 4x grl-ifd. Twenty-five adg clones were randomly selected from a large population and were crossed with 2x clone W5295.7, which produces 2n pollen by parallel spindles (ps). The 4x progenies from 4x*2x crosses were used to determine the genotypes at the ps locus by screening 10-20 plants in each family for 2n pollen. Based on chromosome segregation at the ps locus, 9, 14, 1, and 1 clones were nulliplex, simplex, simplex or duplex, and duplex, respectively. The frequency of the ps gene in the adg population was estimated to be 0.825 and 0.815 for chromosome and chromatid segregation, respectively. The high frequencies of 2n pollen and the ps gene in cultivated 2x and 4x groups, and in wild taxa closely related to them, provide evidence for sexual polyploidization in the tuber-bearing Solanums. PMID- 24227238 TI - Nucleus substitution between Petunia species using gamma ray-induced androgenesis. AB - The ovaries of two different Petunia species: Petunia hybrida (hort) and Petunia parodii (Steere) were irradiated with tau-ray doses ranging from 50 to 1,000 Gy before pollination. Seed setting occurred after 4 days preculture on a non sterile medium. Ovaries transformed into fruits were then cultivated aseptically with the following results: (1) tau-ray doses ranging from 200 to 1,000 Gy led to the development of two types of plants: haploids 2n=x=7 and overdiploids 2n>2x=14. (2) The androgenetic origin of haploids was ascertained by using genetic markers. The origin of overdiploids is discussed. (3) Androgenetic haploids contained the chloroplasts of the irradiated female parent. No visible change of cp DNA patterns was observed after irradiation. (4) The four possible androgenetic events were successfully obtained between the two Petunia species: hybrida haploids with hybrida or parodii cytoplasm, and parodii haploids with parodii or hybrida cytoplasm. PMID- 24227239 TI - The isolation, characterization and application in the Triticeae of a set of wheat RFLP probes identifying each homoeologous chromosome arm. AB - To investigate the use of RFLP analysis in the Triticeae, a set of low copy number probes has been isolated from a wheat cDNA library. The probes identify each of the 14 homoeologous chromosome arms of wheat as determined by analysis of DNA fragments hybridizing to the probes in aneuploid lines of Chinese Spring. These probes can be used in RFLP analyses both for the assignment of homoeology of alien chromosomes or arms added to wheat, and for the determination of chromosome dosage in wheat aneuploids. Different chromosomes from various Triticeae species can therefore be followed in a wheat genetic background using a single technique. The potential uses of the set in facilitating the transfer of alien segments into wheat are outlined. PMID- 24227240 TI - The chromosomal location of a third set of malate dehydrogenase loci, Mdh-3, in wheat, barley and related species. AB - A third set of malate dehydrogenase loci have been identified and located on the short arms of homoeologous group 5 chromosomes in wheat. Allelic differences have been found at each of the three Mdh-3 loci. However, Mdh-D3 appears to be least variable, with a second allele found only in Sears' 'Synthetic' among a survey of 42 varieties. Homoeoloci were identified on chromosome 7 (5H) of Hordeum vulgare, the short arm of 5E in Agropyron elongatum and 5U in Aegilops umbellulata. PMID- 24227241 TI - High molecular weight glutenin subunit in durum wheat (T. durum). AB - The diversity of high molecular weight (HMW) glutenin subunits of 502 varieties of durum wheat (Triticum durum) from 23 countries was studied using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Twenty-nine types of patterns were observed with 18 mobility bands. A total of 18 alleles were identified by comparing the mobilities of their subunits to those previously found in hexaploid wheat (T. aestivum) and in Triticum turgidum var. dicoccum. Five new alleles were detected: two on the Glu A1 and three on the Glu B1 locus. Comparison of the frequency of alleles in the three species T. aestivum, T. dicoccum and T. durum was investigated. Significant differences exist between each of these species on the basis of the frequency distributions of their three and four common alleles at the Glu A1 and Glu B1 locus, respectively. The Glu B1c allele occuring very frequently in hexaploid wheats was not found in the two tetraploid species. More than 83% of the T. durum analysed were found to have the Glu A1c (null) allele. PMID- 24227242 TI - Genetic and environmental considerations for evaluating crown position of wheat. AB - Crown position affects winter survival of fallsown wheat (Triticum aestivum L.) Direct or indirect selection for crown depth has been little practiced. Reports have suggested that short subcrown internode length was closely related to semidwarf plant height and that semidwarfism was related to poor emergence. This study determined the relationships among crown depth, plant height, and emergence rate index in three wheat populations. The efficiency of evaluating crown placement in the field was examined and additional information was obtained on its genetic control. The F2-derived F4 and F5 lines from the crosses of female parents 'Daws', 'Nugaines', and 'Stephens' with male parent 'Selection 7952' were planted at Central Ferry and Pullman, Washington, respectively. Correlations from each population indicated that crown depth and subcrown internode length were not closely associated with plant height and emergence rate index. Crown depth was a more reliable indicator of crown placement than subcrown internode length. Adjustment of the data for seed depth differences was essential for evaluating subcrown internode length but less important for evaluating crown depth. After adjustment for seed depth, narrow-sense h (2) values for subcrown internode length and crown depth were 0.25-0.41. Crown depth and subcrown internode length were inherited as quantitative traits in phenotypes that expressed variable dominance. Modest gains due to selection for crown depth were achieved. PMID- 24227243 TI - Additive genetic variance within populations derived by single-seed descent and pod-bulk descent. AB - Breeders of self-pollinated legumes commonly use single-seed descent (SSD) or pod bulk descent (PBD) to produce segregating populations of highly inbred individuals. We presented equations for the expected value of the additive genetic variance within populations derived by SSD (E(V A)SSD) and PBD (E(V A)PBD) in terms of the initial population size (N 0), the number of seed harvested per pod (M), the probability of survival of an individual (theta), and the generation at which the population is evaluated (S t). Differences between (E(V A)SSD) and (E(V A)PBD) are due to differences in the expected amount of random drift which occurs with the two methods after the S 0 generation. With both methods, random drift occurs when progeny are sampled from heterozygous parents. An additional component of random drift occurs when sampled progeny fail to survive during SSD, or when sampling occurs amoung families during PBD. For values of N 0, M, theta, and S t that are typical of soybean (Glycine max (L.) Merr.) breeding programs, (E(V A)SSD) will be greater than (E(V A)PBD). The ratio of (E(V A)SSD) to (E(V A)PBD) will: (1) increase as M and theta increase; (2) approach a value of 1.00 as N 0 increases; and (3) be a curvilinear function of S t. Plant breeders should compare SSD and PBD based upon values of (E(V A)SSD) and (E(V A)PBD) and the expected cost of carrying out the two methods. PMID- 24227244 TI - Expression and fate of CAT reporter gene microinjected into fertilized medaka (Oryzias latipes) eggs in the form of plasmid DNA, recombinant phage particles and its DNA. AB - Fertilized medaka (Oryzias latipes) eggs were cytoplasmically injected with the chloramphenicol acetyltransferase (CAT) gene encompassed in supercoiled and linear plasmid DNA, as well as in intact recombinant phage particles and DNA isolated from the phage. Expression for the CAT plasmid DNA was highest at the gastrula/neurula stage, while for the DNA of the phage, it peaked in the 1-week old embryo; then expression declined but was still detectable in early adulthood (4 weeks post injection). Following the fate of exogenous DNA, an extensive replication was observed in early embryogenesis, and DNA was still found 4 weeks after injection, suggesting a possibility of integration. The system is useful as a transient expression system for the analysis of early developmental genes in particular, but also as a test system for the analysis of cloned genes of interest for the farming of economically important fish species. The fact that DNA transferred in intact phage particles or its DNA is functionally active opens the possibility to introduce larger DNA pieces (20 kb), e.g., for the functional test of larger and more distant control regions. PMID- 24227245 TI - Efficient design of crossbreeding experiments. AB - The efficiencies of different experimental configurations for estimating additive (A) and heterotic (H) effects in purebred and crossbred populations derived from two parent breeds are examined. Allocation of resources over six groups is considered: the two parental breeds, the F1, the F2 and the backcrosses to the two parental breeds. Additive and heterotic effects are best estimated by allocating resources to the two parental groups and F1 in the proportions 35%, 35%, 30% and for many practical situations, an experiment involving numbers in the region 250-300 is reasonable. If it is not possible to include all three groups, other combinations involving a subset of them and some of the other three groups can be used to give estimates of A and H. However, even the best of these alternatives requires over twice the resources to give the same precision as the optimal design and, further, these estimates may be correlated. Relatively modest reallocation of resources to the F2 to estimate or test for an epistatic effect (E) leads to a minor reduction in the precision of estimates of A and H while giving reasonable precision for the estimate of E. The inclusion of maternal effects in the model greatly reduces the efficiency of estimation of A and H. Where one of the breeds is introduced through the sire line only, optimal allocation gives roughly equal replication to the pure lines and F1 but about 63% of allocation is placed in equal amounts on the two backcrosses produced through crossing F1 dams with pure sires of both breeds. The relevance of these results to the planning of livestock crossbreeding trials, particularly those involving a local and an exotic or imported breed, is discussed. PMID- 24227246 TI - Ribosomal DNA repeat unit polymorphism in 25 Hordeum species. AB - Tandemly repeated DNA sequences containing structural genes encoding ribosomal RNA (rDNA) were investigated in 25 species of Hordeum using the wheat rDNA probe pTA71. The rDNA repeat unit lengths were shown to vary between 8.5 and 10.7 kb. The number of length classes (1-3) per accession generally corresponded to the number of nucleolar organizing regions (NORs). Intraspecific variation was found in H. parodii, H. spontaneum and H. leporinum, but not in H. bulbosum. Restriction analysis showed that the positions of EcoRI, SacI and certain BamHI cleavage sites in the rRNA structural genes were highly conserved, and that repeat unit length variation was generally attributable to the intergenic spacer region. Five rDNA BamHI restriction site maps corresponded to the following groups of species: Map A - H. murinum, H. glaucum, H. leporinum, H. bulbosum, H. marinum, H. geniculatum; Map B - H. leporinum; Map C - H. vulgare, H. spontaneum, H. agriocrithon; Map D - H. chilense, H. bogdanii; and Map E - remaining 14 Hordeum species. The repeat unit of H. bulbosum differed from all other species by the presence of a HindIII site. The closer relationship of H. bulbosum to H. leporinum, H. murinum and H. glaucum than to H. vulgare was indicated by their BamHI restriction maps. PMID- 24227247 TI - Autopolyploidy in Dactylis glomerata L.: further evidence from studies of chloroplast DNA variation. AB - Chloroplast DNA variation has been used to examine some of the maternal lineages involved in the evolution of the intraspecific polyploid complex, Dactylis glomerata L. Diploid (2x) and tetraploid (4x) individuals were collected from natural populations of the subspecies glomerata (4x), marina (4x) and lusitanica (2x), as well as from sympatric 2x/4x populations of the Galician type. Digestion of their ctDNA with 11 restriction endonucleases revealed enough variation to characterise three ctDNA variants, designated MBMK, MBmK and mBMK. The distribution of these ctDNA variants reflects different stages in their spread among the populations. The MBMK ctDNA variant predominated at both ploidy levels in subspecies glomerata, lusitanica and marina, and in recent tetraploid Galician/glomerata hybrids. The MBmK variant was detected in a single tetraploid individual and probably results from a relatively recent mutation. Fixation of the mBMK minority variant in the diploid and tetraploid Galician populations adds to the evidence concerning the possible origin of the Galician tetraploids. It means that the Galician diploids were maternal ancestors of the tetraploids. This result complements evidence from earlier studies based on morphology or biochemical markers, and reduces the likelihood that the tetraploids arose by hybridisation between an ancient Galician diploid and an alien tetraploid. It is, however, consistent with a true autopolyploid origin of the tetraploids. PMID- 24227248 TI - Evidence for the existence of 2n gametes in Lotus tenuis Wald. et Kit. (2n=2x=12): their relevance in evolution and breeding of Lotus corniculatus L. (2n=4x=24). AB - Crosses between male sterile L. corniculatus (2n=4x=24) and L. tenuis (2n=2x=12) plants were performed in order to verify the presence of 2n gametes in L. tenuis. All but one of the plants from these crosses had 2n=4x=24 and the L. corniculatus phenotype; this plant had 2n=2x=12 and the L. tenuis phenotype. The plants also showed good quantity of pollen at tripping, good pollen fertility and good percentage of seed setting in the backcross to L. corniculatus. On the whole, both cytological and morphological observations, showing that all but one of the plants from L. corniculatus x L. tenuis were normal tetraploids, suggest the existence of diploandrous gametes in L. tenuis. On the other hand, haploid parthenogenesis probably gave origin to the dihaploid plant 2n=2x=12. PMID- 24227249 TI - Partitioning of variation derived from tissue culture of winter wheat. AB - The presence of somaclonal variation is well documented in wheat, but information is needed which identifies point(s) during the tissue culture process at which variation is most likely induced. Field experiments were designed to partition the total somaclonal variation among three potential sources: single embryo derived calli, regenerant (R0) plants of a common embryo-derived callus, and spike-derived lines of a common R0 plant. Three populations of winter wheat ('TAM 105', 'Vona', and 'KS75210') totaling 72 lines were evaluated in replicated drilled plots in the R2 and R3 generations. The principal source of variation was influenced by parent genotype. Considering all traits, somaclonal variation in the 'TAM 105' and 'Vona' populations was predominantly attributed to tillers from the same regenerant plant. This source, as well as the original R0 plant source, contributed to variation in the 'KS75210' population, depending on the trait measured. Embryos did not consistently provide a significant source of variation. The presence of somaclonal variation was not always associated with a downward shift in population mean compared to parental controls. Significant population increases were noted for spike density and biomass, and some lines showed significantly higher grain protein content without a yield reduction, but these responses were again genotype-specific. PMID- 24227250 TI - Variability and correlations in muskmelon in relation to the cultivation method. AB - Six fruit characters have been measured in 23 cultivars of Cucumis melo, representing a wide geographical range. Plants were grown both in the greenhouse and in the field. When the 23 cultivars were analyzed together, the largest component of variance was found between cultivars under both growth conditions, suggesting the existence of large genetic diversity for all the characters studied. Generally, variance between plants within cultivars was less than or equal to variance between fruits within plant. This indicates that environmental variation is the most important part of the variation within cultivars. Correlations between pairs of characters at cultivar, plant and fruit levels were calculated from the variance-covariance components. In the majority of paired traits, the correlation values indicated that genetic and environmental factors may act in the same direction. PMID- 24227251 TI - C-banding pattern and powdery mildew resistance of Triticum ovatum and four T. aestivum-T. ovatum chromosome addition lines. AB - C-banding patterns of T. ovatum (Ae. ovata) and four T. aestivum cv 'Poros'-T. ovatum chromosome addition lines are presented, and the added chromosomes of T. ovatum have been identified. Furthermore, nucleolar activity and powdery mildew resistance were analyzed in the 'Poros'-ovatum addition lines and compared to that of T. ovatum and T. aestivum cv 'Poros'. The addition lines II, III and IV and 'Poros' were highly susceptible to powdery mildew isolates nos. 8 and 9, whereas the addition lines VI1 and VI2 showed high resistance. Even for an Ml-k virulent isolate, these two lines were highly resistant. By combining the cytological results and those of the powdery mildew analysis, the added chromosomes of T. ovatum can be excluded from responsibility for the high powdery mildew resistance of the addition lines VI1 and VI2. The same is true for a modified chromosome 6B, which is present in the 'Poros'-ovataum addition lines II, III and VI. The high variation in C-banding pattern observed in the A-, B- and D-genome complement of the addition lines is believed to be the result of crossing different lines of T. aestivum instead of 'Poros' alone. Thus, we cannot trace the powdery mildew resistance back to a specific chromosome. PMID- 24227252 TI - Cytological characterization, powdery mildew resistance and storage protein composition of tetraploid and hexaploid 1BL/1RS wheat-rye translocation lines. AB - Progenies of a tetraploid 1BL/1RS wheat-rye translocation line, CV 256, selected from the cross 'Cando' x 'Veery', were analyzed by means of Giemsa C-banding. CV 256 is cytologically stable for the presence of the 1BL/1RS translocation but still segregating for A- and B-genome chromosomes of 'Cando' and 'Veery'. In CV 256, nucleolar activity of the 1RS NOR locus is suppressed, as judged by the absence of a secondary constriction in that rye segment and the capability of organizing nucleoli. PAGE analysis of prolamins confirmed the presence of two 1RS secalins in all single seeds analyzed. SDS-PAGE analysis of reduced glutenins of single seeds indicated that some seeds contained the 'Cando' Glu-B1 locus (subunits 6+8), some contained the 'Veery' Glu-B1 locus (subunits 7+9) while others contained all four subunits, indicating that the material was heterozygous. Pm8 resistance is expressed in the tetraploid 1BL/1RS translocation line based on the reactions of six well-defined powdery mildew isolates. However, Pm8 resistance is not expressed in the hexaploid wheat cultivars 'Olymp', 'Heinrich' and 'Florida', which also contain the 1BL/1RS translocation. Obviously, the existence of the 1BL/1RS translocation is not a proof for the expression of the associated genes. PAGE results did not show a clear linkage between powdery mildew resistance and the presence of 1RS secalins. PMID- 24227253 TI - Induced genetic variability in Rhizobium leguminosarum for nitrogen fixation parameters in Vicia faba L. AB - SUMARY: The objective of this work was to know the behaviour and variability of Rhizobium leguminosarum after irradiation. The induced variation was tested under greenhouse conditions on the variety JV 3 of broad beans (Vicia faba) in six replications. Induced genetic variabilty was observed for strain, parent and mutant versus parent. Out of 24 irradiated strains, strain 93-32 performed better with a greater number of nodules and higher dry weight of nodules per plant and biological yield. Environment played an important role in the expression of characters observed. High heritability and genetic advance of these traits indicated that the nitrogen fixation ability of Rhizobium can easily be improved by selection. PMID- 24227254 TI - Production and cytogenetics of hybrids of Triticum aestivum x Leymus innovatus. AB - Hybrid plants were obtained between Triticum aestivum (2n=6x=42, AABBDD) and Leymus innovatus (2n=4x=28, JJNN) at a frequency varying from 0.4% to 1.2% of the pollinated florets. Improvement of the embryo culture medium resulted in a higher frequency of embryo rescue. Eight of ten hybrids had the expected chromosome number of 35 (ABDJN). Meiotic analysis indicated that there was no homology between the genomes of the two species. Two hybrids had only 28 chromosomes. Comparison of chromosome pairing between the two types of hybrids suggested that Leymus innovatus carries genes that affect chromosome pairing and behavior. The relatively high occurrence of spontaneous doubling in the meiocytes of these hybrids may indicate that backcrossing of the hybrids to wheat should be possible, although frequent chromosome irregularities observed in the meiocytes of the hybrids may decrease the probability of success of this step, which is essential to the process of gene transfer from L. innovatus to wheat. PMID- 24227255 TI - Synthesis of male sterile, triazine-resistant Brassica napus by somatic hybridization between cytoplasmic male sterile B. oleracea and atrazine-resistant B. campestris. AB - Fusion of leaf protoplasts from an inbred line of Brassica oleracea ssp. botrytis (cauliflower, n=9) carrying the Ogura (R1) male sterile cytoplasm with hypocotyl protoplasts of B. campestris ssp. oleifera (cv "Candle", n=10) carrying an atrazine-resistant (ATR) cytoplasm resulted in the production of synthetic B. napus (n=19). Thirty-four somatic hybrids were produced; they were characterized for morphology, phosphoglucose isomerase isoenzymes, ribosomal DNA hybridization patterns, chromosome numbers, and organelle composition. All somatic hybrids carried atrazine-resistant chloroplasts derived from B. campestris. The mitochondrial genomes in 19 hybrids were examined by restriction endonuclease and Southern blot analyses. Twelve of the 19 hybrids contained mitochondria showing novel DNA restriction patterns; of these 12 hybrids, 5 were male sterile and 7 were male fertile. The remaining hybrids contained mitochondrial DNA that was identical to that of the ATR parent and all were male fertile. PMID- 24227257 TI - Multifunctional core-shell structured nanocarriers for synchronous tumor diagnosis and treatment in vivo. AB - Multifunctional, mesoporous, silica-coated upconversion luminescent/magnetic NaGdF4:Yb/Er@NaGdF4:Yb@mSiO2-PEG (referred to as UCNPS; PEG=polyethylene glycol) nanocomposites were fabricated through a phase-transfer-assisted surfactant templating coating process, followed by hydrophilic polymer (PEG) functionalization to improve the stability and biocompatibility. The UCNP core imparts the nanomaterials with luminescence and magnetic properties for simultaneous upconversion optical and magnetic resonance (MR) imaging, whereas the mesoporous shell affords the nanomaterials the ability to load the anticancer drug doxorubicin. Proof-of-principle in vitro and in vivo experiments are presented to demonstrate that the resultant composite nanomaterials can serve as nanotheranostics for synchronous upconversion luminescence/MR dual modal imaging and anticancer drug delivery; this finally realizes the integration of diagnostics and the treatment of cancers. PMID- 24227258 TI - Evolution of lead concentration in the particulate matter of Santiago, Chile, since 1978. AB - Santiago is a city of over 4.5 million inhabitants and about 415000 motor vehicles using leaded gasoline. Twenty-four-hour samples were taken of total and fractionated particulate matter using a low-volume system and two Andersen cascade impactors, between 1978 and 1989 at different sites of the city of Santiago. Lead concentrations were determined by atomic absorption spectrophotometry. The results show that Pb concentrations vary greatly depending on the site selected. Higher values are always detected near the city center. An annual variation with the highest value during the autumn-winter period (May July) is clearly observed. Lead concentrations versus size are clearly biased to particles smaller than 2 um. A correlation is observed between Pb concentrations and the suspended particulate matter under 3 um at different sites of the city. The curves of Pb concentration versus size of the aerosols emitted by the gas exhaust of motor vehicles using leaded gasoline are similar to those of the atmospheric aerosols. PMID- 24227259 TI - A stress-strain model to evaluate the forest situation in Germany and the state of the art of damage research. AB - The situation and the latest findings of forest damage research in Germany are discussed. A newly developed concept for this research is described. This concept allows to identify the drawbacks of the recent damage research concept but also the integration of results compiled up to now. The importance for including natural occurring stress factors such as climate, soil conditions or local situation of individual species is outlined. PMID- 24227260 TI - Survey and evaluation of contaminants in earthworms and in soils derived from dredged material at confined disposal facilities in the Great Lakes Region. AB - Soils derived from dredged material were collected, together with earthworms from nine confined disposal facilities located in the Great Lakes Region. These samples were analyzed for 18 elements, 11 organochlorine pesticides, PCBs, and 24 polycyclic aromatic hydrocarbons. The concentrations detected in earthworms were evaluated in terms of their potential hazard to wildlife, which for the sake of the evaluation were assumed to prey entirely either on earthworms or on other soil invertebrates having similar concentrations. The soil concentrations (dry wt.) of the contaminants of greatest concern were <1.9 to 32 ppm Cd, <0.053 to 0.94 ppm Hg, 4.6 to 550 ppm Pb, and <0.1 to 1.0 ppm PCBs. The concentrations in earthworms (dry wt., ingested soil included) were as high as 91 ppm Cd, 1.6 ppm Hg, 200 ppm Pb, and 1.8 ppm PCBs. Based on laboratory toxicity studies of relatively sensitive species, and on concentration factors calculated from the earthworm and soil data, we estimated that lethal or serious sublethal effects on wildlife might be expected at concentrations of 10 ppm Cd, 3 ppm Hg, 670 ppm Pb, and 1.7 ppm PCBs in alkaline surface soils derived from dredged material. Concentrations of polycyclic aromatic hydrocarbons in earthworms were well below those in soil. PMID- 24227261 TI - A real-time monitoring system for Kerava river quality. AB - The hygienic quality of the water of the Kerava river, southern Finland, deteriorates occasionally. The purpose of the study was to design a real-time monitoring system that would inform the public using the river for recreational purposes about the changes in water quality. The system was constrained to consist of on-line sensing of water quality and quantity, and adjacent forecasting models. Four different system alternatives were analyzed and compared. The first alternative observes river flow in real-time; the second alternative also monitors water temperature, turbidity, pH, conductivity and dissolved oxygen. The data collected in this way are used to forecast Streptococcus and E. coli concentrations, using canonical correlation and regression analysis. The third configuration is a two-step procedure, where river flow is first predicted by an ARMAX model and the hygienic state is then based on the flow estimate, as in the first assemblage. The most expensive monitoring system, which at present is the least well-known, is to apply the Lidar system, where the hygienic status of the river quality is observed directly using laser technology, placing less emphasis on modeling. In this paper, the alternatives are formulated and a preliminary comparison is made, using the criteria of operational feasibility, prediction uncertainty, investment and maintenance costs, and suitability for in-situ monitoring. PMID- 24227262 TI - Metals in feathers of brown noddy (Anous stolidus): Evidence for bioaccumulation or exposure levels? AB - Levels of environmental pollution are generally assumed to be greater in nearshore and estuarine habitats compared to the open ocean. This difference presumably derives from high inputs from industrial and agricultural sources entering estuaries and bays from rivers and as direct runoff. This suggests that levels of heavy metals should be higher in birds that obtain their food resources from nearshore habitats rather than the open ocean far from land. I compared the levels of lead, cadmium, mercury and selenium in feathers of young and adult brown noddies (Anous stolidus) along the coast of Oahu, Hawaii. Prior to fledging, young noddies obtain all their food resources from their parents that bring back fish and squid from a few km offshore, whereas adults spend much of the year outside the breeding season on the open ocean, where they obtain most of the metals that accumulate in their feathers. For all metals, the young noddies had lower levels than adults. These data do not support the hypothesis that heavy metal pollution is greater nearshore than on the open ocean, but further investigation is needed to distinguish simple biaccumulation with age from differential exposure by habitat, and contamination from the birds own secretions during preening and from the outside. PMID- 24227263 TI - Evidence for long-term migration on the Balkan Peninsula using dental and cranial nonmetric data: Early interaction between corinth (Greece) and its colony at Apollonia (Albania). AB - This article seeks to identify "Greeks" and "non-Greeks" in "mixed" mortuary contexts in a Greek colony. Specifically, we test the hypothesis that Illyrian and Greek individuals lived and were buried together at the Corinthian colony of Apollonia, Albania (established ca. 600 BC). The pattern of human biological interaction at Apollonia is tested by identifying variation in genetic relatedness using biodistance analysis of dental and cranial nonmetric traits for three sites: Apollonia (n = 116), its founder-city Corinth (n = 69), and Lofkend (n = 108), an inland site near Apollonia pre-dating colonization. Logistic regression analysis estimates that individuals from colonial Apollonia are most closely related to prehistoric Illyrian populations (from Lofkend and prehistoric Apollonia), rather than Greeks (from Corinth). The phenotypic similarity between colonial Apollonia and prehistoric Illyria suggests that there was a large Illyrian contribution to the gene pool at the colony of Apollonia. However, some trait combinations show low biological distances among all groups, suggesting homogeneity among Illyrian and Greek populations (assessed through pseudo Mahalanobis' D(2) ). The degree of phenotypic similarity suggests shared ancestry and long-term migration throughout these regions. The impacts of missing data and small sample sizes are also considered. PMID- 24227264 TI - The evolution of gender. PMID- 24227265 TI - A multidisciplinary approach to the study of the plasma membrane of Zea mays pollen during controlled dehydration. AB - A multidisciplinary approach (freeze-fracture, nuclear magnetic resonance, differential scanning calorimetry, isoelectric focusing and fluorochromatic reaction test) has been used to follow the behaviour of Zea mays pollen during dehydration - and to estimate its quality. At anthesis, the water content of maize pollen is 57-58% and the vegetative plasma membrane is continous and well structured with a very low density of intramembraneous particles on the extraplasmic fracture face. Maize pollen grains can withstand the drying process until a water content of 28% is reached, at which point 60-80% of the individuals show a negative reaction in the fluorochromatic test. At this water content, there is no more crystallizable water and thus metabolism decreases, leading to oxidative damage and the formation of gelphase microdomains in the plasma membrane. Consequently, the plasma-membrane permeability is modified. At 15-13% water content, all pollen grains show a negative fluorochromatic reaction, and gel-phase microdomains are more numerous but membranes still have a bilayer structure. Relaxation-time experiments indicate the occurrence of water replacement at the membrane level. Thus, sugar may stabilize the membrane structure at water contents as low as 3%. During the dehydration process, pollen walls act as elastic structures and remain closely applied to the protoplast. The combination of wall deformation and water replacement would permit pollen survival until oxidative damage occurs in the dehydrated grain. PMID- 24227266 TI - Somatic instability of carotenoid biosynthesis in the tomato ghost mutant and its effect on plastid development. AB - The tomato (Lycopersicon esculentum (L.) Mill.) ghost plant is a mutant of the San Marzano cultivar affected in carotenoid biosynthesis. ghost plants exhibit a variable pattern of pigment biosynthesis during development. Cotyledons are green but true leaves are white. Green sectors, which appear to be clonal in origin, are frequently observed in the white tissue. Because of the lack of photosynthesis ghost plants have a very low viability in soil. We have developed a strategy for propagating ghost plants that employs organ culture to generate variegated green-white plants which, supported by the photosynthetic green areas, develop in soil to almost wild-type size. These plants were used to analyze the pigment content of the different tissues observed during development and plastid ultrastructure. Cotyledons and green leaves contain both colored carotenoids and chlorophyll but only the colorless carotenoid phytoene accumulates in white leaves. the plastids in the white tissue of ghost leaves lack internal membrane structures but normal chloroplasts can be observed in the green areas. The chromoplasts of white fruits are also impaired in their ability to form thylakoid membranes. PMID- 24227267 TI - Pathway of assimilate transfer between mesophyll cells and minor veins in leaves of Cucumis melo L. AB - Photoassimilating mature leaves of Cucumis melo exported carbon at a rate of 1.7 mg C.dm(-2).h(-1). Radiolabeling with (14)C showed that stachyose and raffinose are the main carbohydrates translocated. Autoradiograms indicated that sieve elements of the abaxial phloem of minor veins are the sole conduits for carbon export from mature leaves and carbon import into immature leaflets. Sieve elements of the abaxial phloem are associated with intermediary cells which are intimately connected with the surrounding mesophyll cells by numerous plasmodesmata. Photoassimilate, labeled with (14)C, was released into the leaf apoplast and could be trapped in a buffer solution circulating over the abraded adaxial epidermis. Carbon efflux was 1% of the carbon-export rate. A comparable distribution of (14)C among the sugars, amino acids and organic acids, recovered from the free space and from leaf extracts, was recorded. The composition of released (14)C-labeled carbohydrates in the free space resembled the pattern of photoassimilate, but differed clearly from the translocate. Release of organic compounds into the leaf apoplast was stimulated by chelating agents like Na-ATP, ethylenediaminetetraacetic acid and ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid; a correlation between carbon efflux into the apoplast and carbon export from the leaf was not detected. It is suggested that the release of organic compounds into the leaf apoplast of Cucumis melo is the consequence of a general leakage from mesophyll and vascular parenchyma cells. A selective release of transport oligosaccharides was not observed. The experimental results presented here do not preclude a symplastic transfer of assimilates in mature leaves. PMID- 24227268 TI - Microtubule cytoskeleton in intact and wounded coenocytic green algae. AB - Microtubule (MT) arrangements were investigated, with immunofluorescence and electron microscopy, in two related species of coenocytic green algae. Intact cells of both Ernodesmis verticillata (Kutzing) Boergesen and Boergesenia forbesii (Harvey) Feldmann have two morphologically distinct populations of MTs: a highly regular cortical array consisting of a single layer of parallel, longitudinal MTs; and perinuclear MTs radiating from the surface of the envelope of each interphase nucleus. In both algae, mitotic figures lack perinuclear MTs around them. Pre-incubation with taxol does not alter the appearance of these arrays. The cortical and nuclear MTs appear to coexist throughout the nuclear cycle, unlike the condition in most plant cells. At the cut/contracting ends of wounded Ernodesmis cells, cortical MTs exhibit bundling and marked convolution, with some curvature and slight bundling of MTs throughout the cell cortices. In Boergesenia, wound-induced reticulation and separation of the protoplasm into numerous spheres also involves a fasciation of MTs within the attenuating regions of the cytoplasm. Although some cortical MTs are fairly resistant to cold and amiprophos-methyl-induced depolymerization, the perinuclear ones are very labile, depolymerizing in 5-10 min in the cold. The MT cytoskeleton is not believed to be directly involved in wound-induced motility in these plants because amiprophos methyl and cold depolymerize most cortical MTs without inhibiting motility. Also, the identical MT distributions in intact cells of these two algae belie the very different patterns of cytoplasmic motility. Although certain roles of the MT arrays may be ruled out, their exact functions in these plants are not known. PMID- 24227269 TI - Secretion and membrane recycling in plant cells: novel intermediary structures visualized in ultrarapidly frozen sycamore and carrot suspension-culture cells. AB - Freeze-fracture electron microscopy of propane-jet-frozen samples has been employed to investigate vesicle-mediated secretion and membrane recycling events in carrot (Daucus carota L.) and sycamore maple (Acer pseudoplatanus L.) suspension-culture cells. Stabilization of the cells by means of ultrarapid freezing has enabled us to preserve the cells in a turgid state and to visualize new intermediate membrane configurations related to these events. Indeed, many of the observed membrane configurations, such as flattened membrane vesicles with slit-shaped membrane fusion sites and horseshoe-shaped membrane infoldings, appear to result from the action of turgor forces on the plasma membrane. Individual cells exhibited great variations in numbers and types of membrane configurations postulated to be related to secretion and membrane-recycling events. In the majority of cells, the different membrane profiles displayed a patchy distribution, and within each patch the membrane configurations tended to be of the same stage. This result indicates that secretory events are triggered in domains measuring from 0.1 to about 10 MUm in diameter. Based on an extensive analysis of the different membrane configurations seen in our samples, we have formulated the following model of vesicle-mediated secretion in plant cells: Fusion of a secretory vesicle with the plasma membrane leads to the formation of a single, narrow-necked pore that increases in diameter up to about 60 nm. During discharge, the vesicle is flattened, forming a disc-shaped structure perpendicular to the plane of the plasma membrane. As the vesicle is flattened, the pore is converted to a slit, the maximum length of which coincides with the diameter of the flattened vesicle. The flattened vesicle then tips over and concomitantly the plasma-membrane slit becomes curved into a horseshoe-shaped configuration as it extends along the outer margins of the tipped-over vesicle. Some coated pits are present interspersed between the above-mentioned structures, but their numbers appear insufficient to account for an exclusively endocytotic mechanism of membrane recycling. Instead, our micrographs are more consistent with a mixed mode of recycling of membrane components to the cortical endoplamic reticulum and to Golgi cisternae that involves both internalization of membrane by endocytosis and of individual lippid molecules by unknown mechanisms (lipid exchange proteins?). To this end, overall flattening out of the horseshoe-shaped membrane infoldings is accompanied by a retraction and reduction in size of their central, tongue-like structure. PMID- 24227270 TI - Microcallus growth from maize protoplasts. AB - Maize (Zea mays L.) protoplasts obtained from Type I and Type II calli from several genotypes were shown to be capable of synthesizing cell walls and forming small clusters of cells. The medium used also supported cluster formation from protoplasts obtained from root tips. The effects of various additions to the medium (such as casein hydrolysate, coconut water, amino acids, sugars, phytohormones, nitrate, calcium, and dimethylsulfoxide as well as pH variations on cellcluster formation were determined. The method of culture (protoplasts plated in agarose or supported in alginate beads in liquid medium) as well as several components of the medium were found to be critical for microcallus formation. Protoplasts obtained from embryogenic Type I callus and cultured in the medium of C. Nitsch and J.P. Nitsch (1967, Planta 72, 355-370) modified by various additions (NN 67-mod medium) were affected most by various sugars, casein hydrolysate, coconut water, and a combination of the auxins napthalene-1-acetic acid (2 mg/l) and 2,4-dichlorophenoxyacetic acid (0.1 mg/l), and the cytokinin N(6)-benzylaminopurine (0.5 mg/l). Cluster size in the agarose culture system was from 0.1 to 0.5 mm diameter and in the alginate culture system, up to 2.0 mm diameter. PMID- 24227271 TI - Fast photoacoustic transients from dark-adapted intact leaves: oxygen evolution and uptake pulses during photosynthetic induction - a phenomenology record. AB - Using a photoacoustic technique it has been possible to observe fast oxygen evolution and uptake transients at a high time resolution (approx. 0.2 s), when a dark-adapted leaf is reilluminated. There is initially a rapid pulse of oxygen evolution, correlated with the initial fluorescence rise (total duration under the experimental conditions used about 1-2 s), corresponding presumably to the photoreduction of the plastoquinone pool. This phenomenon may be utilized to calibrate the oxygen-evolution photoacoustic signal. The first pulse is followed by a series of slower bursts of oxygen uptake and evolution, reflecting various pools which are expressed following sequential activation of various parts of the photosynthetic apparatus, until achievement of a steady state. PMID- 24227272 TI - Phloem unloading in tobacco sink leaves: insensitivity to anoxia indicates a symplastic pathway. AB - Phloem unloading in transition sink leaves of tobacco (Nicotiana tabacum L.) was analyzed by quantitative autoradiography. Detectable levels of labeled photoassimilates entered sink leaves approx. 1 h after source leaves were provided with (14)CO2. Samples of tissue were removed from sink leaves when label was first detected and further samples were taken at the end of an experimental phloem-unloading period. The amount of label in veins and in surrounding cells was determined by microdensitometry of autoradiographs using a microspectrophotometer. Photoassimilate unloaded from first-, second-and third order veins but not from smaller veins. Import termination in individual veins was gradual. Import by the sink leaf was completely inhibited by exposing the sink leaf to anaerobic conditions, by placing the entire plant in the cold, or by steam-girdling the sink-leaf petiole. Phloem unloading was completely inhibited by cold; however, phloem unloading continued when the sink-leaf petiole was steam girdled or when the sink leaf was exposed to a N2 atmosphere. Compartmental efflux-analysis indicated that only a small percentage of labeled nutrients was present in the free space after unloading from sink-leaf veins in a N2 atmosphere. The results are consistent with passive symplastic transfer of photoassimilates from phloem to surrounding cells. PMID- 24227273 TI - Quality of a stress-sensitive Cucurbita pepo L. pollen. AB - The quality of Cucurbita pepo L. pollen was studied using field pollinations and the fluorochromatic-reaction test. The extreme sensitivity of this pollen to dehydration and ageing is demonstrated. Controlled stress applied to mature pollen leads to the development of seedless fruits. Molecular signals seem to be involved in the induction of this parthenocarpy. These results indicate the existence of distinct sequences involved in the completion of the fertilization program of pollen. With pollen altered by stress, the fertilization process may be stopped at different stages of its completion. We bring evidence that Cucurbita pepo plants have developed special adaptations in order to compensate for the poor viability of their pollen. PMID- 24227274 TI - On the properties of fluorescing compounds in guard and epidermal cells of Allium cepa L. AB - Onion guard cells, in contrast to those of Vicia and Pisum, do not require an alkaline treatment in order to fluoresce. Fluorescing compounds of Allium cepa L. were characterized using in-vivo microspectrophotometry; furthermore, invitro chemical analysis for epidermal tissue, intact guard and epidermal cells, and isolated guard-cell protoplasts was performed. The emission intensity (lambdamax 520 nm) decreased when intact onion guard cells were excited with 436 nm light, but increased (lambdamax 470 nm) when excited at 365 nm. This photodecomposition at 436 nm is typical of flavins or flavoproteins whereas an increase in fluorescence intensity with excitation at 365 nm may be explained by the presence of other substances. The presence of flavins could not be unambiguously confirmed from these results. Indeed, the absorption spectra of the vacuolar area of guard cells did not show the peak at 445 nm which is characteristic for flavins. Furthermore, there was no decrease of absorption at the excitation wavelengths of 440 and 330 nm. Since spectral data indicate the presence at high amounts of flavonoids in guard and epidermal cells, this may reduce the sensitivity for the detection of flavins in guard cells. Using thin-layer chromatography and high performance liquid chromatography together with hydrolytic procedures, flavonol glycosides with kaempferol and quercetin as aglycones substituted with sulphate and glucuronate were identified. Further studies on guard-cell metabolism should consider the presence of flavonoids in stomata of onion and other plants. PMID- 24227275 TI - Action spectrum for the blue-light-dependent morphogenesis of hair whorls in Acetabularia mediterranea. AB - In young Acetabularia mediterranea Lamouroux (=A. acetabulum (L.) Silva) the formation of the lateral hair whorls can be induced by a short pulse of blue light after continuous red preillumination. In this paper we describe the experimental conditions for optimum response and the properties of the action spectrum. The probit of the cells which eventually form hair whorls is linearly correlated to the logarithm of the incident quanta of blue light. Parallel fluence-response curves for all wavelengths indicate the involvement of only one photoreceptor pigment. The action spectrum shows no effectiveness of wavelengths above 520 nm, a high action peak at 470 nm and two lower ones at 425 and 370 nm, and is in accordance with those of cryptochrome-like photoreceptors. PMID- 24227276 TI - Changes in cotyledon mRNA during floral induction of Pharbitis nil CV. Violet. AB - Floral induction in seedlings of Pharbitis nil Choisy cv. Violet, with one cotyledon removed, was manipulated by applying various photoperiodic treatments to the remaining cotyledon. Populations of polyadenylated RNA from treated cotyledons were examined to identify messages specifically involved in floral induction. The RNA was translated in vitro using a wheat-germ system, and the resulting translation products were analysed by two-dimensional polyacrylamide gel electrophoresis. Substantial qualitative and quantitative differences were found between mRNA from cotyledons of seedlings kept in continuous light (non induced) and of seedlings given a 16-h dark period (induced). In contrast, inhibition of flowering with a night-break resulted only in one detectable, quantitative difference in mRNA. PMID- 24227277 TI - Kinetic modelling of phototropism in maize coleoptiles. AB - Blue-light-induced phototropism of maize (Zea mays L.) coleoptiles was studied with a view to kinetic models. Red-light-grown plants were used to eliminate complication arising from the activation by blue light of phytochrome-mediated phototropism. In the first part, mathematical models were developed to explain the phototropic fluence-response data, which were obtained for the responses induced by a single unilateral pulse (30 s) and those induced by a unilateral pulse (30 s) given immediately after a bilateral pulse (30 s, fixed fluences). These data showed bell-shaped fluence-response curves, characteristic of "first positive curvature". Modelling began with the assumptions that the light gradient plays a fundamental role in phototropism and that the magnitude of the response is determined by the gradient, or the concentration difference, in a photoproduct between the irradiated and the shaded sides of the tissue. Minimal mathematical models were then derived, by defining chemical kinetics of the photoreaction and introducing the minimum of parameters needed to correlate the incident fluencerate to the functional fluence-rates within the tissue, the functional fluence-rate to the rate constant of the photoreaction, and the photoproduct concentration difference to the curvature response. The models were tested using a curve-fitting computer program. The model obtained by assigning first-order kinetics to the photoreaction failed to explain the fluence-response data, whereas application of second-order kinetics led to a successful fit of the model to the data. In the second part, temporal aspects of the photosystem were examined. Experimental results showed that a high-fluence bilateral pulse eliminated the bell-shaped fluence-response curve for an immediate unilateral pulse, and that the curve gradually reappeared as the time for unilateral stimulation elapsed after the bilateral pulse. The model based on a second-order photoreaction could be extended to explain the results, with assumed changes in two components: the concentration of the reactant for the photoproduct, and the light-sensitivity of the reaction. The reactant concentration, computed with the curvefitting program, showed a gradual increase from zero to a saturation level. This increase was then modelled in terms of regeneration of the reactant from the photoproduct, with an estimated first-order rate constant of about 0.001.s(-1). The computed value for the constant reflecting the light-sensitivity showed a sharp decline after the high-fluence pulse, followed by a gradual return to the initial level. From these analytical results, the appearance of "second positive curvature" was predicted. PMID- 24227278 TI - Calmodulin-like protein from the fern Anemia phyllitidis L. Sw. AB - Spores and prothallia of the fern Anemia phyllitidis L. Sw. contain a protein which in its physicochemical properties corresponds largely to calmodulin. It shows immunoreactivity with a calmodulin antiserum and activates bovine brain phosphodiesterase. Its content increases during the early processes of light induced spore germination, indicating that the Ca(2+)-dependence of these processes may be mediated by this protein. PMID- 24227279 TI - Calcium ions and polyamines activate the plasma membrane-located 1,3-beta-glucan synthase. AB - Sucrose-density-gradient centrifugation and partitioning in a polyethylene glycol/dextran two-phase system were used to isolate plasmamembrane vesicles from microsomal preparations of soybean cell suspension cultures. Both methods resulted in the enrichment of the activity of a 1,3-beta-glucan synthase which forms a polymer consisting of more than 99% of 1,3-linked glucose (callose). Digitonin increases the 1,3-beta-glucan synthase activity in the various membrane fractions to a different degree, supporting the suggestion that this enzyme is vectorially arranged in the plasma membrane. The enzyme is greatly activated either by poly-L-ornithine or synergistically by Ca(2+) and spermine, indicating that the same enzyme is affected and exhibits the regulatory properties necessary for callose synthesis. PMID- 24227280 TI - Signal storage in phytochrome action on nitrate-mediated induction of nitrate and nitrite reductases in mustard seedling cotyledons. AB - Application of nitrate leads to an induction of nitrate reductase (NR; EC 1.6.6.1) and nitrite reductase (NIR; EC 1.7.7.1) in the cotyledons of dark-grown mustard (Sinapis alba L.) seedlings, and this induction can strongly be promoted by a far-red-light pretreatment - operating through phytochrome - prior to nitrate application. This light treatment is almost ineffective - as far as enzyme appearance is concerned - if no nitrate is given. When nitrate is applied, the stored light signal potentiates the appearance of NR and NIR in darkness, even in the absence of active phytochrome, to the same extent as continuous far red light. This action of previously stored light signal lasts for approx. 12 h.Storage of the light signal was measured for NR and NIR. The process shows enzyme-specific differences. Storage occurs in the absence as well as in the presence of nitrate, i.e. irrespective of whether or not enzyme synthesis takes place. The kinetics of signal transduction and signal storage indicate that the formation and action of the stored signal are a bypass to the process of direct signal transduction. Signal storage is possibly a means of enabling the plant to maintain the appropriate levels of NR and NIR during the dark period of the natural light/dark cycle. PMID- 24227281 TI - Erratum. PMID- 24227283 TI - Hydrogen evolution coupled with the photochemical oxygenation of cyclohexene with water sensitized by tin(IV) porphyrins by visible light. AB - Hydrogen evolution coupled with the photochemical oxygenation of cyclohexene with water was observed in the system sensitized by Sn(IV)-porphyrin adsorbed on Pt loaded TiO2 nano-particles in aqueous acetonitrile solution upon visible light irradiation. PMID- 24227282 TI - Expert consensus statement on the use of fractional flow reserve, intravascular ultrasound, and optical coherence tomography: a consensus statement of the Society of Cardiovascular Angiography and Interventions. PMID- 24227284 TI - Mitochondria-targeting oxidovanadium(IV) complex as a near-IR light photocytotoxic agent. AB - Oxidovanadium(IV) complexes [VO(L(1))(phen)].Cl (1) and [VO(L(2))(L(3))].Cl (2), in which HL(1) is 2-{[(benzimidazol-2-yl)methylimino]-methyl}phenol (sal-ambmz), HL(2) is 2-[({1-[(anthracen-9-yl)methyl]-benzimidazol-2-yl}methylimino) methyl]phenol (sal-an-ambmz), phen is 1,10-phenanthroline and L(3) is dipyrido[3,2-a:2',3'-c]phenazine (dppz) conjugated to a Gly-Gly-OMe dipeptide moiety, were prepared, characterized, and their DNA binding, photoinduced DNA cleavage, and photocytotoxic properties were studied. Fluorescence microscopy studies were performed by using complex 2 in HeLa and HaCaT cells. Complex 1, structurally characterized by X-ray crystallography, has a vanadyl group in VO2N4 core with the VO(2+) moiety bonded to N,N-donor phen and a N,N,O-donor Schiff base. Complex 2, having an anthracenyl fluorophore, showed fluorescence emission bands at 397, 419, and 443 nm. The complexes are redox-active exhibiting the V(IV)/V(III) redox couple near -0.85 V versus SCE in DMF 0.1 M tetrabutylammonium perchlorate (TBAP). Complex 2, having a dipeptide moiety, showed specific binding towards poly(dAdT)2 sequence. The dppz-Gly-Gly-OMe complex showed significant DNA photocleavage activity in red light of 705 nm through a hydroxyl radical ((.) OH) pathway. Complex 2 showed photocytotoxicity in HaCaT and HeLa cells in visible light (400-700 nm) and red light (620-700 nm), however, the complex was less toxic in the dark. Fluorescence microscopy revealed the localization of complex 2 primarily in mitochondria. Apoptosis was found to occur inside mitochondria (intrinsic pathway) caused by ROS generation. PMID- 24227285 TI - Whole genome sequencing as a diagnostic test: challenges and opportunities. AB - BACKGROUND: Extraordinary technological advances and decreases in the cost of DNA sequencing have made the possibility of whole genome sequencing (WGS) as a highly accessible clinical test for numerous indications feasible. There have been many recent, successful applications of WGS in establishing the etiology of complex diseases and guiding therapeutic decision-making in neoplastic and nonneoplastic diseases and in various aspects of reproductive health. However, there are major, but not insurmountable, obstacles to the increased clinical implementation of WGS, such as hidden costs, issues surrounding sequencing and analysis, quality assurance and standardization protocols, ethical dilemmas, and difficulties with interpretation of the results. CONTENT: The widespread use of WGS in routine clinical practice remains a distant proposition. Prospective trials will be needed to establish if, and for whom, the benefits of WGS will outweigh the likely substantial costs associated with follow-up tests, the risks of overdiagnosis and overtreatment, and the associated emotional distress. SUMMARY: WGS should be carefully implemented in the clinic to allow the realization of its potential to improve patient health in specific indications. To minimize harm the use of WGS for all other reasons must be carefully evaluated before clinical implementation. PMID- 24227286 TI - Psychology, behavioral sciences, and the challenge to medical education. AB - It is generally agreed that the health care system is in crisis despite reform efforts over the past two decades. Evidence is presented which suggests that medical education has failed successfully to integrate medically relevant behavioral science research findings into medical school curricula or train physicians in the application of behaviorally based treatment technologies. Psychologists in medical education settings have the opportunity to impact medical education and foster psychology's role in health care. If psychology fails to respond to this opportunity, we cannot then complain of the inevitable consequences. PMID- 24227287 TI - Optimism and coping as determinants of psychosocial adjustment to rheumatoid arthritis. AB - Psychosocial adjustment in 66 patients with chronic rheumatoid arthritis, with a mean duration of 12 years with the disease, were evaluated in a prospective design, with 62% of the sample followed up 16 months later. It was predicted that dispositional optimism would predict adjustment over time and that perceived support and perceived control would be related to psychosocial adjustment at the time of concurrent measurement. At Time 1, psychosocial adjustment was associated with greater optimism and perceived support and less disability. Optimism at Time 1 was the only significant predictor of changes in adjustment at Time 2 controlling for Time 1 adjustment and Time 2 disability. It was found that optimism temporally precedes increases in psychosocial adjustment. In terms of coping strategies, wishful thinking was related to poorer social adjustment, whereas problem-focused coping was marginally related to positive adjustment. Neither coping strategy predicted adjustment across time. Optimism at Time 1 did predict problem-focused coping at Time 2. Perceived social support regarding a specific circumstance at a given point in time enables one to persist in solving a task. Interventions to enhance the quality of life of individuals coping with progressive deteriorative disease must look at the influence of their behavior and attitude on those who provide care for them. PMID- 24227288 TI - Psychometric assessment of cardiac transplantation candidates. AB - Psychometric assessment protocols were used to chart the course of 287 end-stage cardiac patients' psychological adjustment at pretransplantation and, again, in 34 who were subsequently transplanted. The regression and repeated-measures analyses suggested that psychological distress is typical of the adult transplantation candidate, although impaired cognitive functioning is more typical of the acute postoperative stage. Negative affect, cognitive, personality, and coping measures are interrelated at pretransplantation; depression and mental control show significant decreases at 2 weeks posttransplantation. Whereas the transplantation process is inherently distressing, psychological testing may identify cognitive and personality features that require more specific clinical attention. PMID- 24227289 TI - Readability of prescription drug labels by older and younger adults. AB - This experiment investigated the readability of medication labels using various combinations of fonts, sizes, and weights of print. Older and younger adult reading speeds and error rates for different print types were compared for both bottle and flat labels. Findings of the study indicated significant differences in reading speed, error rates, and subjective evaluations for print characteristics investigated. Furthermore, the effects of these print characteristics varied for different age groups. Implications of these findings for the design of medication labels for older adults are discussed. PMID- 24227290 TI - Failed back surgeries and minnesota multiphasic personality inventory (MMPI) profiles. AB - MMPI profiles were evaluated for 105 prospective surgical patients who had previously undergone surgery or other procedures for treatment of back pain. Patients were classified into groups having undergone zero, one, two, three, or four or more previous surgeries. While all groups demonstrated a characteristicsomatogenic profile, none of the MMPI validity or clinical scales significantly differentiated the groups and there was no relationship between increased number of surgeries and MMPI scale characteristics. These results support the nonoptimistic prognostication of thesomatogenic MMPI profile for surgical intervention for back pain but show no clear relationship of MMPI profile characteristics to degree of experience of previously failed surgery. PMID- 24227291 TI - Personality disorder correspondence between the million behavioral health inventory (MBHI) and the minnesota multiphasic personality inventory (MMPI). AB - The MBHI and MMPI personality disorder scales were analyzed for convergent and discriminant validity. Correlational data demonstrated that six of the eight scales were significantly related, while the remaining two scales approached significance. Further analyses of these data, however, demonstrated that none of the scales correlated significantly better with its convergent scale compared to nonconvergent scales. The MBHI classified significantly more of the sample as personality disordered (93%) compared to the MMPI personality disorder scales (17%). Furthermore, the MBHI tended to describe the sample as falling within the Anxious cluster of personality disorders, whereas the MMPI described them within the Dramatic cluster. Single scale codetype correspondence was found to be 15%, while two-point concordance was 12.5%, indicating very low congruence between personality style codetypes. These two measures do not appear to be measuring the same personality style constructs. PMID- 24227292 TI - Determination of fluoroquinolones in bovine milk samples using a pipette-tip SPE step based on multiwalled carbon nanotubes prior to CE separation. AB - A simple CE-UV method was developed for the simultaneous determination of ciprofloxacin, norfloxacin, and ofloxacin in milk samples. The optimum separation was obtained using a 20 mM ammonium dihydrogenphosphate solution with 2 mM cetyltrimethylammonium bromide at pH 3.0 as the BGE. Satisfactory resolution for structurally very similar analytes, like norfloxacin and ciprofloxacin, was achieved without including any organic solvent. Milk samples were prepared using a simple/extraction procedure based on acidic protein precipitation followed by an SPE step using only 5 mg of multiwalled carbon nanotubes as the sorbent material. The LODs for the three compounds were between 7.5 and 11.6 MUg/L and the RSDs for the peak areas were between 2.6 and 4.9%. The complete method was applied to spiked real milk samples with satisfactory recoveries for all analytes (84-106%). PMID- 24227295 TI - Social closure, aggressive behavior, and cuticular hydrocarbon profiles in the polydomous antCataglyphis iberica (hymenoptera, Formicidae). AB - Nestmate recognition was studied in the polydomous antCataglyphis iberica (Formicinae) in the laboratory. The study examined six colonies collected from two different populations 600 km apart in the Iberian peninsula (Barcelona and Murcia). Introduction of an alien worker into an allocolonial arena always ended in death to the intruder, demonstrating that in this species societies are extremely closed. Dyadic encounters composed of individuals from different colonies in a neutral arena confirmed the existence of high aggression between allocolonial individuals. We also investigated variability in the composition of the major cuticular hydrocarbons between the colonies used in the behaviorial tests. There were marked quantitative differences between the profiles of ants from the two populations, suggesting that the populations are completely segregated. Cuticular profiles within a population tended to be more similar, but were nevertheless colony specific. The degree of colony closure inC. iberica seemed to be independent of geographic distance since aggression between the colonies was always at its maximum, irrespective of their population origin. PMID- 24227294 TI - Statistical testing of shared genetic control for potentially related traits. AB - Integration of data from genome-wide single nucleotide polymorphism (SNP) association studies of different traits should allow researchers to disentangle the genetics of potentially related traits within individually associated regions. Formal statistical colocalisation testing of individual regions requires selection of a set of SNPs summarising the association in a region. We show that the SNP selection method greatly affects type 1 error rates, with published studies having used methods expected to result in substantially inflated type 1 error rates. We show that either avoiding variable selection and instead testing the most informative principal components or integrating over variable selection using Bayesian model averaging can help control type 1 error rates. Application to data from Graves' disease and Hashimoto's thyroiditis reveals a common genetic signature across seven regions shared between the diseases, and indicates that in five of six regions associated with Graves' disease and not Hashimoto's thyroiditis, this more likely reflects genuine absence of association with the latter rather than lack of power. Our examination, by simulation, of the performance of colocalisation tests and associated software will foster more widespread adoption of formal colocalisation testing. Given the increasing availability of large expression and genetic association datasets from disease relevant tissue and purified cell populations, coupled with identification of regulatory sequences by projects such as ENCODE, colocalisation analysis has the potential to reveal both shared genetic signatures of related traits and causal disease genes and tissues. PMID- 24227293 TI - A general framework for association tests with multivariate traits in large-scale genomics studies. AB - Genetic association studies often collect data on multiple traits that are correlated. Discovery of genetic variants influencing multiple traits can lead to better understanding of the etiology of complex human diseases. Conventional univariate association tests may miss variants that have weak or moderate effects on individual traits. We propose several multivariate test statistics to complement univariate tests. Our framework covers both studies of unrelated individuals and family studies and allows any type/mixture of traits. We relate the marginal distributions of multivariate traits to genetic variants and covariates through generalized linear models without modeling the dependence among the traits or family members. We construct score-type statistics, which are computationally fast and numerically stable even in the presence of covariates and which can be combined efficiently across studies with different designs and arbitrary patterns of missing data. We compare the power of the test statistics both theoretically and empirically. We provide a strategy to determine genome wide significance that properly accounts for the linkage disequilibrium (LD) of genetic variants. The application of the new methods to the meta-analysis of five major cardiovascular cohort studies identifies a new locus (HSCB) that is pleiotropic for the four traits analyzed. PMID- 24227296 TI - Effect of ethanol and alpha-pinene on response of ambrosia beetle,Trypodendron lineatum, to lineatin-baited funnel and drainpipe traps. AB - The response ofT. lineatum to ethanol and alpha-pinene, when used with the pheromone lineatin, was tested for two trap types. Funnel traps, which are passive barrier traps, caught significantly more beetles than drainpipe traps, which require an active response by the beetle to enter the trap. However, the response ofT. lineatum to the semiochemical treatments did not significantly differ for the two trap types. Treatments that included alpha-pinene with the pheromone, either with or without ethanol, caught significantly moreT. lineatin than those with the pheromone alone. When ethanol and or alpha-pinene were added to the pheromone significantly more female beetles were trapped than with pheromone alone. Male-female ratios were significantly lower for both types of traps when ethanol was included in the bait than for lineatin alone or with alpha pinene. A higher percentage of male beetles entered the drainpipe traps than was captured with funnel traps. PMID- 24227297 TI - Role of prey odor in food recognition by rock crabs,Cancer irroratus say. AB - Rock crabs,Cancer irroratus, respond to food odors in low concentration as measured by changes in antennular flicking rate. The responses of rock crabs to prey odor were tested in the presence and absence of visual cues to determine the role of chemical cues in prey recognition. Crabs were attracted to the source of mussel odor introduced into one arm of a Y maze. Natural and artificial prey shells and resin boxes were presented to crabs with and without the presence of mussel extract. The crabs were able to see, handle, and manipulate these objects. Crabs opened and consumed contents that emitted chemosensory cues and ignored identical objects that did not. Rock crabs were attracted to food odors and are capable of utilizing chemical cues to detect, locate, and identify food items. PMID- 24227298 TI - Structures and allelopathic effects ofNuphar alkaloids: Nupharolutine and 6,6' dihydroxythiobinupharidine. AB - Two of the majorNuphar alkaloids, nupharolutine and 6,6' dihydroxythiobinupharidine, were isolated from the aquatic perennial herbNuphar lutea (L.) Sibth. & Sm., yellow water lily. In a lettuce seedling bioassay of the two pure compounds, the former was inactive and the latter was highly inhibitory of radicle elongation at concentrations greater than 2 ppm. Structures and stereochemistry of the two compounds were confirmed by DEPT,(1)H-(1)H COSY,(1)H (13)C COSY, and(1)H-(1)H NOESY experiments. PMID- 24227299 TI - Resorcinol in exudates ofNuphar lutea. AB - Resorcinol (1,3-dihydroxybenzene) was identified as one of the major constituents of the exudate ofNuphar lutea seedlings, which were raised from seeds and cultivated under axenic conditions. The compound is released from the plants in considerable amounts (up to 15 nmol/seedling/day). Highest rates of resorcinol exudation were measured when the seedlings were incubated under physiological conditions (macronutrient and light supply) that resembled those of natural stands of the plant. An inverse correlation exists between nitrate and/or light supply and resorcinol production. Because of its generally toxic properties, resorcinol is suggested to play a role as an allelochemical in interactions between macrophytes and other organisms of the aquatic ecosystem. A first approach of resorcinol application to zooplankton and phytoplankton organisms resulted in deleterious effects against aDaphnia species. Two Cryptophyceae species reduced resorcinol concentration to zero, showing a concomitant increase of the size of starch granule enclosures. Cyanophyceae and Chlorophyceae seemed not to be affected. PMID- 24227300 TI - Identification of sex pheromones from cowpea weevil,Callosobruchus maculatus, and related studies withC. analis (coleoptera: Bruchidae). AB - Female cowpea weevils,Callosobruchus maculatus, produce a sex pheromone that elicits orientation and sexual behavior in males. Bioassay-directed isolation of the sex pheromone was conducted and compounds in the active fraction were identified and synthesized. Volatiles were collected from individual virgin females by adsorption on filter paper dises and hexane extraction. A bioassay was used in which the locomotory response of single males in glass vials was recorded upon exposure to treatments or controls. Crude extracts were subjected to silica gel column chromatography with solvents of increasing polarity; all activity eluted with methanol. Activity in the highly polar methanol fraction suggested a carboxylic acid or a compound with multiple polar functionality. Acid-base partitioning of the crude extract isolated all activity in the acid fraction, confirming that the pheromone was a carboxylic acid. The acid fraction was further fractionated by preparative GC with a Carbowax column. The most active GC fraction contained the following five 8-carbon acids identified by GC-MS and comparison with synthetic candidates: 3-methyleneheptanoic acid, (Z)-3-methyl-3 heptenoic acid, (E)-3-methyl-3-heptenoic acid, (Z)-3-methyl-2-heptenoic acid, and (E)-3-methyl-2-heptenoic acid. Each of the synthetic acids was active individually for males, and combinations of two or more of the acid pheromones had an additive effect. Upwind flight responses to natural and synthetic pheromones were observed in a flight tunnel. (Z)-3-Methyl-2-heptenoic acid was previously identified as the sex pheromone for the relatedC. analis, but this and the other four acid pheromones fromC. maculatus were inactive for maleC. analis. There was no cross-attraction betweenC. maculatus andC. analis in reciprocal studies using extracted volatiles from females of both species, GC-MS analysis ofC. analis female volatiles failed to detect any of theC. maculatus compounds but did find an unidentified C-8 acid with a GC retention time different from any of theC. maculatus pheromones. PMID- 24227301 TI - The pheromone of the eastern tent caterpillar,Malacosoma americanum (F.) (lepidoptera, Lasiocampidae). AB - The pheromone system of the eastern tent caterpillar,M. americanum, has been identified as a mixture of (E,Z)-5,7-dodecadienal and the corresponding alcohol. Field data on the attractiveness of the aldehyde alone were not consistent, but mixtures of aldehyde and alcohol in varying proportions were attractive to males. Addition of small amounts ofE,Z acetate toE,Z aldehyde had no effect on male response, but larger amounts reduced trap catch. Traps baited withZ,E, E,E, orZ,Z aldehydes were not more attractive than blank traps. Pherocon IC traps fortified with extra adhesive and baited with lures consisting of 500 ug (E,Z)-5,7 dodecadienal with either 250 or 100 ug of the corresponding alcohol trapped as many as 100 males/trap/night with means of 15-20. Lures prepared from purified (94%E,Z) aldehyde and alcohol were more attractive than those prepared from unpurified (58%E,Z) materials. PMID- 24227302 TI - Sex phermone components of mulberry looper,Hemerophila atrilineata butler (lepidoptera: Geometridae). AB - (6Z-9S, 10R)-Epoxy-octadecene (SR-1) and (3Z, 6Z-9S, 10R)-epoxy-octadecadiene (SR 2) are sex pheromone components of the mulberry looper (MBL),Hemerophila atrilineata Butler. Compounds extracted from female MBL pheromone glands were identified by coupled gas chromatographic-electroantennographic detection (GC EAD) and GC-mass spectrometry. In field experiments in China,SR-2,RS-2, or both combined were hardly attractive, butSR-2 in combination withSR-1 attracted significant numbers of MBL males. Synergistic behavioral activity ofSR-1 plusSR 2, but not of corresponding antipode mixtures, indicates enantiospecificity of MBL pheromone communication. Because blends of racemic and enantiospecific (SR)1 plus2 were similarly attractive, racemic1 plus2 may have potential for mass trapping or confusion of MBL males in commercial mulberry plantations. PMID- 24227303 TI - Aggregation pheromone system of nymphal gregarious desert locust,Schistocerca gregaria (forskal). AB - Hexanal, octanal, nonanal, decanal, hexanoic acid, octanoic acid, nonanoic acid, and decanoic acid were identified in the volatile emissions from fifth instars ofSchistocerca gregaria by coupled gas chromatography-electroantennography (GC EAD) detection and coupled GC-mass spectrometry (MS). In laboratory assays, synthetic blends of the eight compounds, with acids and aldehydes tested separately, evoked strong aggregation responses from fifth instars, similar to responses evoked by a crude volatile extract of the nymphs. A nymphal fecal volatile phenolic blend of guaiacol and phenol, which we have previously shown to evoke an aggregative response from different stages of the insect, significantly synergized the activity of the blend of eight compounds, suggesting mutually augmentative roles for nymphal and fecal volatiles in evoking aggregation. These results indicate that the aggregation behavior of gregarious second to fifth instars is modulated by three sets of pheromonal compounds: aldehydes and acids emitted by the nymphs themselves and phenols associated with their feces. PMID- 24227304 TI - Some chemical bases for gypsy moth,Lymantria dispar, larval rejection of green ash,Fraxinus pennsylvanica, foliage as food. AB - Green ash is one of the few tree species rejected as food by larvae of the generalist gypsy moth,Lymantria dispar L. (Lepidoptera: Lymantriidae). Such rejection is based especially on chemicals present in green ash foliage. The gypsy moth larval feeding-inhibitory activity is contained in the ethyl acetate extractables of green ash foliage. Three representative columnchromatographed fractions of the extractables contained antifeedant activity. Individual fractions showed weaker antifeedant activity compared to the total ethyl acetate extractables. Acid hydrolysis of the extractables destroyed antifeedant activity and yielded feeding stimulant activity at higher concentrations. The aqueous extractables were not feeding-inhibitory. Compounds in the green ash extractables were separated by TLC, HPLC, CC, and GC. PMID- 24227305 TI - Olfactory responses ofIps plastographus maritimus lanier (coleoptera: Scolytidae) to insect and host-associated volatiles in the laboratory. AB - Attraction of both sexes ofIps plastographus maritimus Lanier to bark-phloem xylem discs of Monterey pine,Pinus radiata D. Don, was demonstrated in the laboratory. Increasing concentrations of male and female volatiles trapped separately and released in a one-to-one ratio decreased attraction for both sexes combined. Attraction of both sexes to volatiles derived from males and females tunneling together in a one-to-one ratio increased with increasing concentration of extract. Attraction of males and females to male-infested discs and to trapped male volatiles increased with increasing dose of males or male extract. Attraction of males and females to female-infested discs and to trapped female volatiles was also demonstrated. The presence of females in male galleries reduced the attractiveness of infested disks to both sexes combined. Increasing numbers of females, tunneling separately from males in the same disc, reduced attraction of males, but not females. When a constant attractive dose of male volatiles was released with increasing doses of female volatiles, there was no difference in response of either sex when female volatiles were present compared with the response to male volatiles alone. When a constant attractive dose of male volatiles was released with increasing concentrations of volatiles derived from males and females tunneling together in a one-to-one ratio, attraction ofI. p. maritimus decreased. Response of females was frequently higher than that of males to the same attractant source. Hence, both sexes produce an attractant, and both sexes tunneling together in the same gallery reduce attraction of males and females to an attractive dose of male attractant. PMID- 24227306 TI - Comparative study of hermit crab responses to shell-related chemical cues. AB - The responses of Australian hermit crabs to two types of shell-related odor cues were compared. Introduction of gastropod snail odor elicited an increase in grasping of shells in all four species tested (Clibanarius infraspinatus, C. taeniatus, C. virescens, andDiogenes avarus). However, the magnitude of response in the case ofC. virescens was significantly lower than the responses of individuals of the other species. Individuals ofC. infraspinatus responded to introduction of conspecific hemolymph with an increase in both locomotion and the frequency of grasping of shells.C. infraspinatus also responded to the hemolymph of the other three species, and there were no differences in the magnitude of the responses depending upon the source of the hemolymph. When individuals ofC. infraspinatus were exposed to snail odor and conspecific hemolymph at the same time, the responses were indistinguishable from those shown to hemolymph alone. PMID- 24227307 TI - 3-Methyl-alpha-himachalene: Proposed structure for novel homosesquiterpene sex pheromone ofLutzomyia longipalpis (diptera: Psychodidae) from Jacobina, Brazil. AB - The principal behaviorally active volatile component (ca. 90% +) of the sex pheromone glands ofLutzomyia longipalpis from Jacobina. Brazil, has been isolated and characterized as a novel homosesquiterpene with the structure 3-methyl-alpha himachalene (C16H26). A minor component (ca. 10%) of the gland extract has also been identified as the sesquiterpenealpha-himachalene (C15H24). This work confirms that there are at least 3 members of theL. longipalpis species complex. PMID- 24227308 TI - Quantification of contact oviposition stimulants for black swallowtail butterfly,Papilio polyxenes, on the leaf surfaces of wild carrot,Daucus carota. AB - Ovipositing black swallowtail butterflies,Papilio polyxenes, make their final host-selection decisions on the basis of compounds present on the leaf surface. Little information is available, however, on the chemistry of leaf surfaces. The purpose of this study was to develop a technique to extract and quantify the concentrations of compounds from the leaf surfaces ofDaucus carota, one of the main host species forP. polyxenes, with particular reference to compounds already identified as contact oviposition stimulants, namelytrans-chlorogenic acid (CA) and luteolin-7-O-(6"-O-malonyl)-beta-D-glucopyranoside (L7MG), as well as its degradation product luteolin-7-glucoside (L7G). Plant surfaces were extracted by dipping leaves sequentially in pairs of solvents: (1) CHCl3-MeOH, (2) near boiling H2O, (3) CHCl3-near-boiling H2O, and (4) CH2Cl2-CH2Cl2. The resulting extracts were fractionated and analyzed using high-performance liquid chromatography. The leaf-surface concentrations of each compound were calculated using regressions relating leaf surface area to leaf weight that were obtained from measurements of field-collected carrot plants. All four methods removed the three compounds from carrot leaf surfaces, but the solvent systems differed in effectiveness. The chloroform-near-boiling water solvent system performed better than the other solvent combinations, but not significantly so. This system also extracted the highest number of polar, UV-absorbing compounds. Methylene chloride was significantly less efficient than the other methods. An additional test confirmed that the chloroform-near-boiling water method removed compounds from the surface alone and probably not from the apoplast or symplast. Surface concentrations of CA (up to 600 ng/cm(2) leaf surface) were substantially greater than those of the two flavonoid compounds. No clear seasonal trend in concentrations was evident from the limited number of sampling dates. PMID- 24227309 TI - Determination of feeding preference of Formosan subterranean termite (Coptotermes formosanus Shiraki) for some amino acid additives. AB - A choice feeding test using 21 amino acids was conducted to determine the feeding preference of Formosan subterranean termite,Coptotermes formosanus Shiraki, in the laboratory. Significantly more filter paper treated withD-aspartic acid orL glutamic acid was consumed by Formosan subterranean termites than was control filter paper treated with water. In two-choice feeding tests, termites consumed significantly more filter paper treated withD-aspartic acid orL-aspartic acid than paper treated with water. AddingL-proline,L-lysine, orL-isoleucine to filter paper significantly increased consumption compared with control filter paper in no-choice tests. The use of amino acid additives in termite baits is briefly discussed. PMID- 24227310 TI - FGF7 signals are relayed to autocrine EGF family growth factors to induce branching morphogenesis of mouse salivary epithelium. AB - BACKGROUND: The Matrigel-embedded epithelium of the mouse submandibular gland undergoes branching morphogenesis when cultured in medium supplemented with fibroblast growth factor 7 (FGF7) and lysophosphatidic acid (LPA), whereas it elongates a stalk with limited branching in medium with only FGF7. Because LPA is a well-known activator of epidermal growth factor (EGF) signaling, we hypothesized the involvement of autocrine EGF family growth factors in the branching morphogenesis. RESULTS: Reverse transcriptase polymerase chain reaction studies showed that three members, Tgfa, Hbegf,and Nrg1 of the EGF family were expressed in the epithelium cultured with FGF7 + LPA as well as in the epithelium freshly isolated from the rudiments. All the growth factors induced extensive branching morphogenesis in the Matrigel-embedded epithelium in the presence of LPA. Tyrphostin AG112, an inhibitor of EGF signaling, severely impaired branching morphogenesis induced by FGF7 + LPA without exogenous addition of EGF family growth factors to the culture medium. The shaking cultures, which were expected to decrease the concentration of autocrine growth factors near the epithelium by promoting their diffusion, significantly reduced branching morphogenesis induced by FGF7 + LPA. CONCLUSIONS: Autocrine EGF family growth factors are involved in epithelial branching morphogenesis induced by FGF7 + LPA. PMID- 24227312 TI - Volumetric quantification of fluid flow reveals fish's use of hydrodynamic stealth to capture evasive prey. AB - In aquatic ecosystems, predation on zooplankton by fish provides a major pathway for the transfer of energy to higher trophic levels. Copepods are an abundant zooplankton group that sense hydromechanical disturbances produced by approaching predators and respond with rapid escapes. Despite this capability, fish capture copepods with high success. Previous studies have focused on the predatory strike to elucidate details of this interaction. However, these raptorial strikes and resulting suction are only effective at short range. Thus, small fish must closely approach highly sensitive prey without triggering an escape in order for a strike to be successful. We use a new method, high-speed, infrared, tomographic particle image velocimetry, to investigate three-dimensional fluid patterns around predator and prey during approaches. Our results show that at least one planktivorous fish (Danio rerio) can control the bow wave in front of the head during the approach and consumption of prey (copepod). This alters hydrodynamic profiles at the location of the copepod such that it is below the threshold required to elicit an escape response. We find this behaviour to be mediated by the generation of suction within the buccopharyngeal cavity, where the velocity into the mouth roughly matches the forward speed of the fish. These results provide insight into how animals modulate aspects of fluid motion around their bodies to overcome escape responses and enhance prey capture. PMID- 24227311 TI - Investigation of nerve injury through microfluidic devices. AB - Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment. PMID- 24227313 TI - Incidence of unplanned admissions after sinonasal surgery: a 6-year review. AB - BACKGROUND: There has been an increasing transition from hospital-based surgeries to ambulatory surgery center (ASC)-based surgeries. A significant portion of ASC cases are otolaryngological procedures, with sinonasal surgery as one of the most common procedures. However, admissions into the hospital from the ASC can be difficult for the patient and the provider. This study evaluates the incidence of unplanned admissions after sinonasal surgery in a 6-year period and identifies the factors for these admissions. METHODS: A retrospective study was conducted of patients who had ambulatory sinonasal surgeries from January 2007 to December 2012 at Weill Cornell Medical Center/New York Presbyterian Hospital performed by the senior author (A.K.). Electronic medical records were reviewed for age, gender, procedure/surgery performed, and admission and/or discharge information. RESULTS: A total of 750 patients who underwent sinonasal surgeries from January 2007 to December 2012 were eligible for review. The study sample had a mean age of 46 years and 55.6% were male. There were a total of 24 admissions, of which 6 were unplanned (0.8%). Reasons for unplanned admissions included pain (most common, 50%), followed by epistaxis, nausea, and other. CONCLUSION: The rate for unplanned admissions for sinonasal surgeries was 0.8%, which is lower than the national rate (2.65%), indicating that sinonasal surgeries are appropriate as ambulatory cases. Because the reason for unplanned admission was highest for pain, patients should be further evaluated for more effective methods of pain control postoperatively or preemptively. PMID- 24227314 TI - Quantitation of microbial growth on surfaces. AB - An equation describing the initial phases of microbial surface colonization is presented. Simultaneous microbial attachment and growth are considered as the primary components of colonization. A table is given that permits determination of growth rate from the density and distribution of cells present on surfaces after incubation in situ. Other methods used to calculate microbial growth rate on surfaces are evaluated. The new procedure is more accurate and less time consuming than those used previously. Published data on microbial surface colonization more closely follow the proposed colonization equation than the exponential growth equation, which overestimates the growth rate. PMID- 24227315 TI - Specificity of bacterial symbionts in Mediterranean and Great Barrier Reef sponges. AB - Bacteria were isolated from marine sponges from the Mediterranean and the Great Barrier Reef and characterized using numerical taxonomy techniques. A similar sponge-specific bacterial symbiont was found in 9 of 10 sponges examined from both geographic regions. This symbiont occurred in sponges of two classes and seven orders, and it probably has been associated with sponges over a long geological time scale. Another symbiont apparently specific to the spongeVerongia aerophoba was found. This sponge is yellow-orange, similar in color to the bacterial symbiont. These symbionts are two of a large mixed bacterial population present in many sponges. PMID- 24227316 TI - Identification and population dynamics of bacteria in symptomatic oat leaves. AB - Bacteria isolated from symptomatic oat leaves included pseudomonads,Erwinia herbicola, and others.Pseudomonas coronafaciens was isolated predominantly from leaves with halo blight symptoms or necrotic spots. Leaves with red leaf symptoms yielded many types of bacteria, including saprophytic pseudomonads,P. syringae, E. herbicola, Bacillus sp.,Micrococcus sp.,Corynebacterium sp., a yeast, and other unidentified species. Only isolates ofP. coronafaciens were pathogenic on the plant hosts tested. The bacteria associated with red leaf symptoms exist as saprophytes and/or epiphytes on leaves with those symptoms. It is concluded that bacteria do not contribute to red leaf symptom development in oats, but symptomatic leaves provide an environment for their growth. PMID- 24227317 TI - Trichoderma hamatum: Its hyphal interactions withRhizoctonia solani andPythium spp. AB - The mode of hyphal interaction and parasitism ofPythium spp. andRhizoctonia solani byTrichoderma hamatum was studied by both phase-contrast and Nomarski differential interference-contrast microscopy. Directed growth of the mycoparasite toward its host was observed. In the area of interaction,T. hamatum produced appressorial-like structures attached to the host cell wall. Subsequently, several different types of interactions occurred.T. hamatum either grew parallel to and along the host hypha or coiled around its host. In the contrast regions the parasite formed bulbular or hook-like structures that contained granular cytoplasm. In other cases the parasite penetrated into and grew within the mycelium ofR. solani orP. ultimum. As a consequence of the attack, the host hypha became vacuolated, shrank, collapsed, and finally disintegrated. These observations suggest the involvement of parasitism followed by lysis rather than involvement of antibiotics in this host-mycoparasite relationship. PMID- 24227318 TI - Occurrence and activity of iron- and sulfur-oxidizing microorganisms in alkaline coal strip mine spoils. AB - Spoils samples collected from a coal strip mine in southeastern Montana were examined for populations and activities of iron- and sulfur-oxidizing bacteria. Spoils examined were of three types: (a) acidic pyrite-rich waste coal, (b) oxidation halo material, and (c) alkaline material, which was the most widespread type. Bacterial numbers, sulfur oxidation, and(14)CO2 uptake activity declined to low levels in the summer when spoils were dry. Even in wetter spring months pyritic spoils contained relatively low numbers of acidophilic iron- and sulfur oxidizing bacteria, probably indicative of water stress since the same spoils incubated with excess water or dilute mineral salts showed considerably greater bacterial numbers and activity. Certain wells in coal and spoils aquifers contained substantial populations of iron-oxidizing acidophilic bacteria. However, these wells were always of alkaline or neutral pH, indicating that bacterial pyrite oxidation occurred where groundwaters contacted either replaced spoils or coal that contained pyrite or other metal sulfides. Bacterial activity may contribute to trace metal and sulfate leaching in the area. PMID- 24227319 TI - A pressure-retaining deep ocean sampler and transfer system for measurement of microbial activity in the deep sea. AB - A deep ocean sampler (DOS) has been developed for microbiological sampling and is capable of aseptically collecting 400-ml water samples from any depth in the world oceans. The instrument maintains samples under in situ pressure and temperature. A hyperbaric transfer system has also been developed, enabling transfer of sample volumes up to 150 ml, without decompression or dilution, to pressurized incubation chambers. Utilization of(14)C-glutamate (21 to 96MUg/l) and(14)C-acetate (4.6MUg/l) by microbial populations in undecompressed water samples from the N.W. Atlantic and the Cape and Angola Basins was recorded over incubation periods of 2 to 18 weeks. Rates of substrate utilization ranged from 1 to 38*10(-2) MUg/l/day. PMID- 24227320 TI - Filterable marine bacteria found in the deep sea: Distribution, taxonomy, and response to starvation. AB - A significant number of viable colony-forming bacteria were recovered from deep ocean bottom water samples passed through a 0.45MUm filter. However, these bacteria small enough to pass through a 0.45MUm membrane filter and termed "filterable bacteria" were less abundant in open-ocean surface water and coastal water samples. The reduced size of bacterial cells present in deep-ocean bottom water samples was documented by scanning electron microscopy. The concentration of ATP in the water samples was found to be correlated with results of direct counts of bacteria.Numerical taxonomy of bacterial strains isolated from water samples collected at two stations in the deep sea yielded taxonomic clusters grouped according to sample and size fraction. The generic composition of bacterial populations of bottom water filtrates was compared with that of bacteria retained by 0.45MU m filters. Strains ofAlcaligenes, Flavobacterium, Pseudomonas, andVibrio spp. were identified among those retained by, as well as passing through, 0.45MUm filters.Two marine isolates obtained from the filtrate of a deep-ocean water sample were incubated for 9 weeks in nutrient-free artificial seawater, during which the cells became rounded and reduced in size. After the 9-week incubation period, more than 10% of the viable cells of both cultures were able to pass through a 0.4MUm filter. The viable count at 9 weeks wasca. 10% of that of the initial population, although from direct counts the total population number remained relatively constant throughout the incubation period. From the observed reduction in cell size and increased starvation resistance of cells held under low nutrient conditions, it is concluded that a significant relationship exists between decreased cell size and increased survival of marine bacteria in the deep sea. PMID- 24227321 TI - Barophilic growth of bacteria from intestinal tracts of deep-sea invertebrates. AB - Digestive tracts of abyssal scavenging amphipods and a deep-sea holothurian were examined for the presence of intestinal microflora capable of rapid proliferation under in situ pressures of 430 to 520 atmospheres (atm) and temperatures of 3-5 degrees C. For two amphipod specimens, population doubling times of 5 and 6 hours were observed under in situ conditions, compared to 8 and 6 hours, respectively, at 1 atm. Growth enhancement under pressure was related inversely to initial population size and directly to concentration of available nutrient. In the case of the deposit-feeding holothurian, attached bacteria scraped from the intestinal lining showed a doubling time, under pressure, of 11 hours, compared to 36 hours for transient sediment bacteria that comprised the gut contents. These data suggest that deep-sea animals possess a commensal gut flora capable of responding to increased nutrient levels, via feeding of the host, without inhibition by the elevated hydrostatic pressures encountered in the deep ocean environment. PMID- 24227322 TI - Hydrodynamic radius alone governs the mobility of molecules through plasmodesmata. AB - Various fluorescent molecular probes have been injected into the cytoplasm of nectary trichome cells of Abutilon striatum to ascertain the conductivity of the plasmodesmata. Most of the probes were based on fluorescein conjugated to a range of amino acids and peptides. The probes are not broken down by cytoplasmic enzymes during the period of observation. The results indicate that there are no specific effects of aromatic amino acids, either polar or hydrophobic types, on the conductivity of the Abutilon plasmodesmata, contrary to reports for other plants. The conductivity of the plasmodesmata in the trichomes is slightly greater than for any that have been studied in the tissues of other plants. It is proposed that in Abutilon the mobility of a probe is determined solely by the effective Stokes radius of the molecule, and that the radius of the molecule is governed by the molecular weight and, in particular, by the nature of the side groups in the peptide chain attached to the fluorochrome. Calculations are presented which indicate that channels between material in the plasmodesmatal annulus are the most likely route for the diffusion of the probes, and that the width of individual channels in the annulus is close to 3 nm. PMID- 24227323 TI - Localization of membrane-associated calcium during development of fucoid algae using chlorotetracycline. AB - During the first day of development, fertilized eggs of fucoid algae generate an embryonic axis and commence rhizoid growth at one pole. Using Fucus distichus (L.) Powell, F. vesiculosus L. and Pelvetia fastigiata (J.Ag.) DeTony we have investigated the role of calcium in axis formation and fixation as well as in tip growth. The intracellular distribution of membrane-associated calcium was visualized with the fluorescent calcium probe chlorotetracycline (CTC). Punctate fluorescence associated with organelle-like structures was found in conjunction with diffuse staining at all developmental stages. This membrane-associated calcium remained uniformly distributed throughout the cortical cytoplasm while the axis was established, but increased in the rhizoid protuberance at germination. In subsequent development, fluorescence was restricted to the cortical cytoplasm at the elongating tip and at sites of crosswall biosynthesis.The requirement for Ca(2+) uptake during development was investigated through inhibition studies; influx was impaired with transport antagonists or by removal of extracellular calcium. Both treatments curtailed germination and tip elongation but had little effect on axis polarization. Reductions in external calcium that interfered with elongation also markedly reduced the apical CTC fluorescencence, indicating that calcium uptake and localization are prerequisites for tip growth. This apical Ca(2+) is probably involved in the secretory process that sustains tip elongation. By contrast, calcium was not implicated in the generation of an embryonic axis. PMID- 24227324 TI - Comparison of the effect of excessive light on chlorophyll fluorescence (77K) and photon yield of O2 evolution in leaves of higher plants. AB - High-light treatments (1750-2000 MUmol photons m(-2) . s(-1)) of leaves from a number of higher-plant species invariably resulted in quenching of the maximum 77K chlorophyll fluorescence at both 692 and 734 nm (F M, 692 and F M, 734). The response of instantaneous fluorescence at 692 nm (F O, 692) was complex. In leaves of some species F O, 692 increased dramatically in others it was quenched, and in others yet it showed no marked, consistent change. Regardless of the response of F O, 692 an apparently linear relationship was obtained between the ratio of variable to maximum fluorescence (F V/F M, 692) and the photon yield of O2 evolution, indicating that photoinhibition affects these two variables to approximately the same extent. Treatment of leaves in a CO2-free gas stream containing 2% O2 and 98% N2 under weak light (100 MUmol . m(-2) . s(-1)) resulted in a general and fully reversible quenching of 77K fluorescence at 692 and 734 nm. In this case both F O, 692 and F M, 692 were invariably quenched, indicating that the quenching was caused by an increased non-radiative energy dissipation in the pigment bed. We propose that high-light treatments can have at least two different, concurrent effects on 77K fluorescence in leaves. One results from damage to the photosystem II (PSII) reaction-center complex and leads to a rise in F O, 692; the other results from an increased non-radiative energy dissipation and leads to quenching of both F O, 692 and F M, 692 This general quenching had a much longer relaxation time than reported for DeltapH-dependent quenching in algae and chloroplasts. Sun leaves, whose F V/F M, 692 ratios were little affected by high-light exposure in normal air, suffered pronounced photoinhibition when the exposure was made under conditions that prevent photosynthetic gas exchange (2% O2, 0% CO2). However, they were still less susceptible than shade leaves, indicating that the higher capacity for energy dissipation via photosynthesis is not the only cause of their lower susceptibility. The rate constant for recovery from photoinhibition was much higher in mature sun leaves than in mature shade leaves, indicating that differences in the capacity for continuous repair may in part account for the difference in their susceptibility to photoinhibition. PMID- 24227325 TI - Transport of sugars across the plasma membrane of beetroot protoplasts. AB - Protoplasts isolated from beetroot tissue took up glucose preferentially whereas sucrose was transported more slowly. The (14)C-label from [(14)C]glucose and [(14)C]sucrose taken up by the cells could be detected rapidly in phosphate esters and, after feeding of [(14)C]glucose was found also in sucrose. The temperature-dependent uptake process (activation energy EA about 50 kJ . mol(-1)) seems to be carrier mediated as indicated by its substrate saturation and, for glucose, by competition experiments which revealed positions C1, C5 and C6 of the D-glucose molecule as important for effective uptake. The apparent Km(20 degrees C) for glucose (3-O-methylglucose) was about 1 mM whereas for sucrose a significantly lower apparent affinity was determined (Km about 10 mM). When higher concentrations of glucose (5 mM) or sucrose (20 mM) were administered, the uptake process followed first-order kinetics. Carrier-mediated transport was inhibited by N,N'-dicyclohexylcarbodiimide, Na-orthovanadate, p chloromercuribenzenesulfonic acid, and by uncouplers and ionophores. The uptake system exhibited a distinct pH optimum at pH 5.0. The results indicate that generation of a proton gradient is a prerequisite for sugar uptake across the plasma membrane. Protoplasts from the bundle regions in the hypocotyl take up glucose at higher rates than those derived from bundle-free regions. The results favour the idea that apoplastic transport of assimilates en route of unloading might be restricted to distinct areas within the storage organ (i.e. the bundle region) whereas distribution in the storage parenchyma is symplastic. PMID- 24227326 TI - Control of photoassimilate movement in source-leaf tissues of Ipomoea tricolor Cav. AB - Autoradiographs obtained from discs from mature, peeled Ipomoea tricolor Cav. leaves indicated that a 15-min 2 mM p-chloromercuribenzene sulfonic acid (PCMBS) pretreatment did not prevent the accumulation of (14)CO2-derived (14)C photosynthate within the minor veins. However, accumulation of (14)C photosynthate within these veins was almost, or completely prevented by treatment of the leaf discs at pH 9.0. Peeled Ipomoea leaf discs were also used to study the kinetics of exogenously supplied [(14)C]sucrose; influx occurred by the combined operation of a saturable and a first-order kinetic mechanism. Both transport mechanisms were inhibited by a 15-min 2 mM PCMBS pretreatment or by treatment at pH 9.0. An analysis of autoradiographs obtained on leaf discs that had been fed exogenous [(14)C]sucrose, showed that whereas all cells of the leaf took up sucrose at pH 5.0, uptake at pH 9.0 occurred primarily into cells of the minor veins. In contrast with (14)C-photoassimilate experiments, PCMBS pretreatment, at either pH 5.0 or pH 9.0, resulted in a reduction in the radioactivity within the minor veins when the label was supplied exogenously as [(14)C]sucrose. Kinetic experiments conducted with mesophyll cells isolated enzymatically from peeled source-leaf discs indicated that [(14)C]sucrose influx also occurred by a saturable and a first-order kinetic mechanism. Comparative studies between leaf discs and isolated mesophyll cells showed that mesophyll cells could account for 75% of the total uptake occurring into the peeled leaf discs. These results indicate that the effects of PCMBS and alkaline pH on net sucrose uptake by leaf tissues are not exerted solely on phloem tissues, and that some of the effects of these treatments may be attributable to an inhibition of symplasmic transport to the minor veins. PMID- 24227327 TI - Intracellular feruloylation of pectic polysaccharides. AB - The pectic polysaccharides of spinach cell walls carry feruloyl groups on arabinose and galactose residues. The following experiments were designed to discover whether the arabinose residues are feruloylated intra-or extracellularly. Cultured spinach cells started to incorporate exogenous [(3)H]arabinose into polymers at a linear rate after a lag period of approx. 3-4 min, although radioactive polysaccharides and extensin did not start to appear outside the plasmalemma until after an approx. 25-min lag. In the same cells, polysaccharide-bound feruloyl-[(3)H]arabinose units starded to accumulate radioactivity at a linear rate after a lag period of approx. 4-5 min. Therefore, arabinose residues of polysaccharides began to be feruloylated while still intracellular. The rate of formation of polysaccharide-bound feruloyl [(3)H]arabinose units did not appreciably increase after 25 min, showing that any additional extracellular feruloylation of the polysaccharide was relatively slow. This conclusion was supported by two different types of pulse-chase experiments, one of which was designed to detect feruloylation of polysaccharides up to 6 d after synthesis. PMID- 24227328 TI - Comparison of gas chromatography-mass spectrometry, radioimmunoassay and bioassay for the quantification of gibberellin A9 in norway spruce (Picea abies (L.) Karst.). AB - Quantitative estimates of gibberellin A9 in Norway spruce extracts obtained by gas chromatography-mass spectrometry, radioimmunoassay (RIA_ and bioassay were compared after successive purifications of the extracts. The extracts were assayed in several dilutions with and without the addition of standard gibberellin A9, thus showing the effect of extract components on the response of the assays. Radioimmunoassay produced estimates comparable to gas chromatography mass spectrometry after one purification step by high-performance liquid chromatography. Extracts purified by polyvinylpyrrolidone-column chromatography and solvent partitioning but not high-performance liquid chromatography resulted in inaccurate RIA estimates. The performance of the RIA could be monitored by logit-log transformations of the standard curve and extract dilution curve and by calculating the slope of the standard addition curve. It was, however, not possible to correct for the interference caused by extract components by the standard addition procedure. Quantifications by Tan-ginbozu dwarf-rice bioassay were accurate, but a large and unpredictable variation makes it unsuitable for quantitative determinations. PMID- 24227329 TI - Non-photochemical quenching of chlorophyll a fluorescence in isolated chloroplasts under conditions of stressed photosynthesis. AB - Non-photochemical quenching of chlorophyll a fluorescence after short-time light, heat and osmotic stress was investigated with intact chloroplasts from Spinacia oleracea L. The proportions of non-photochemical fluorescence quenching (q N ) which are related (q E ) and unrelated (q I ) to the transthylakoid proton gradient (DeltapH) were determined. Light stress resulted in an increasing contribution of q Ito total q N.The linear dependence of q. Eand DeltapH, as seen in controls, was maintained. The mechanisms underlying this type of quenching are obviously unaffected by photoin-hibition. In constrast, q Ewas severely affected by heat and osmotic stress. In low light, the response of q Eto changes in DeltapH was enhanced, whereas it was reduced in high light. The data are discussed with reference to the hypothesis that q Eis related to thermal dissipation of excitation energy from photosystem II. It is shown that q Eis not only controlled by DeltapH, but also by external factors. PMID- 24227330 TI - Evidence for a light-dependent system for reassimilation of photorespiratory CO2, which does not include a C 4 cycle, in the C 3-C 4 intermediate species Moricandia arvensis. AB - Three methods of estimating photorespiratory rate in leaves of the C3-C4 intermediate species Moricandia arvensis and the related C3 species Moricandia moricandioides were compared. The results indicated that the photorespiratory rate in M. arvensis is less than in M. moricandioides, and that this is caused partly by reduced carbon flux through the photorespiratory pathway, and partly by the presence of a mechanism for enhanced photorespiratory CO2 reassimilation in the intermediate species. Measurements of the CO2 compensation point (Gamma) in the two species supported this conclusion. A functional C4 pathway is unlikely to be involved in the reduction of photorespiratory rate in M. arvensis since pulse chase experiments showed that carbon did not move from C4 acids to the reductive pentose-phosphate pathway in attached leaves under steady-state conditions at Gamma. PMID- 24227331 TI - Effects of fusicoccin and abscisic acid on glucose uptake into isolated beetroot protoplasts. AB - Uptake of glucose, 3-O-methylglucose and sucrose into beetroot protoplasts is considerably stimulated by 10(-6)M fusicoccin. This effect is decreased in the presence of 10mM Na(+) or K(+), 2 mM Mg(2+) or Ca(2+). Whereas fusicoccin causes no change in the pH-optimum of the sugar uptake (pH 5.0), the apparent Km of this uptake which obeys a biphasic kinetics is decreased by the action of fusicoccin. In the protoplast suspension, fusicoccin induces an acidification which is suppressed by uncoupling agents. Correspondingly, uncouplers as well as vanadate and diethylstilbestrol markedly inhibit the effect of fusicoccin on sugar uptake. The present data support the view that glucose uptake into beetroot protoplasts depend on the proton-pumping activity of the plasmalemma-ATPase. cis-Abscisic acid diminishes significantly the fusicoccin-enhanced glucose uptake. By using a radioimmunoassay, the internal abscisic acid content of the protoplast was estimated to be in the range of 10(-6) M. Protoplasts isolated from bundle tissue contain twice as much abscisic acid as those derived from storage parenchyma. Because protoplasts from the bundle tissue were shown to take up sugars much faster than those from the storage cells, the observed effect of abscisic acid might reflect an involvement of this hormone in the regulation of carbohydrate partitioning in the beet. PMID- 24227332 TI - Thionin genes specifically expressed in barley leaves. AB - Complementary-DNA (cDNA) clones encoding thionin were identified as one of the most frequent types of clones in a cDNA library constructed from total polyadenylated RNA from young barley leaf cells. One full-length clone codes for a precursor protein that starts with a signal peptide (28 amino acids) followed by the mature thionin (46 amino acids) and terminated by a long acidic extension (63 amino acids). The amino-acid sequence of the leaf thionin is 52% homologous to thionins from barley endosperm and in the C-terminal extension the homology decreases to 41%. In contrast, the leaf thionin is 72% homologous to viscotoxin from mistletoe leaves. Leaf thionin is coded by a multigene family with an estimated nine to eleven genes and analysis of the cDNA clones showed that at least two extremely homologous genes are expressed. Northern hybridization experiments indicate that the leaf thionin genes are not expressed in endosperm and roots. In leaves, the expression of the thionin genes is strongly repressed by light. PMID- 24227333 TI - Sodium efflux from perfused giant algal cells. AB - Internodal cells of the giant alga Chara corallina were perfused internally to replace the native cytoplasm, tonoplast and vacuole with artificial cytoplasm. Sodium efflux from perfused cells, measured by including (22)Na in the perfusion media, was increased by increasing the internal sodium concentration and by decreasing the external pH, and was inhibited by external application of the renal diuretic amiloride. The sodium efflux was markedly ATP-dependent, with a 50 fold decrease in efflux observed after perfusion with media lacking ATP. Efflux in the presence of ATP was reduced by 33% by inclusion of 10 MUM N,N' dicyclohexylcarbodiimide in the perfusion medium. The membrane potential of the perfused cells approximated that of intact cells from the same culture. It is suggested that sodium efflux in perfused Chara cells proceeds via a secondary antiporter with protons, regulated by ATP in a catalytic role and with the proton motive force acting as the energy source. PMID- 24227334 TI - Nuclease sensitivity of storage-protein genes in isolated nuclei of pea seeds. AB - The chromatin structure of legumin genes in nuclei isolated from leaves and cytyledons of pea (Pisum sativum L.) was investigated. Digestions with micrococcal nuclease (EC 3.1.31.1.) showed that the nucleosomal repeat length of total chromatin (171+/-25 base pairs) was similar in nuclei from both tissues. The sensitivity to pancreatic deoxyribonuclease (DNase I; EC 3.1.21.1.) of the legumin genes in cotyledon nuclei was greater than that in leaf nuclei; this increase in sensitivity correlated with transcriptional activity of the genes. No DNase-I-hypersensitive sites were detected in these genes in either tissue. PMID- 24227335 TI - Calcium binding by spinach stromal proteins. AB - Calcium binding to spinach (Spinacia oleracea L.) stromal proteins was examined by dual-wavelength spectrophotometry using the metallochromic indicator tetramethylmurexide. The data are consistent with the existence of at least two, probably independent, classes of binding sites. The total number of binding sites varied between 90-155 nmol.mg(-1) protein with "average" binding constants of 1.1 2.7.mM(-1). Both Mg(2+) and La(3+) inhibited calcium binding competitively, with "average" inhibitor constants of 0.26.mM(-1) and 39.4.mM(-1), respectively; an increase in the potassium concentration up to 50 mM had no effect. In a typical experiment a decrease in pH (7.8 to 7.1) resulted in a decrease in the total number of calcium binding sites from 90 to 59 nmol.mg(-1) protein, but in an increase of the "average" affinity from 2.7 to 4.5.mM(-1). Calculations, using these data and those of Gross and Hess (1974, Biochim. Biophys. Acta 339, 334 346) for binding site I of washed thylakoid membranes, showed that the free Ca(2+) concentration in the stroma under dark conditions, pH 7.1, is higher than under light conditions, pH 7.8. The physiological relevance of the observed calcium binding by stromal proteins is discussed. PMID- 24227336 TI - Wall relaxation in growing stems: comparison of four species and assessment of measurement techniques. AB - This study was carried out to develop improved methods for measuring in-vivo stress relaxation of growing tissues and to compare relaxation in the stems of four different species. When water uptake by growing tissue is prevented, in-vivo stress relaxation occurs because continued wall loosening reduces wall stress and cell turgor pressure. With this procedure one may measure the yield threshold for growth (Y), the turgor pressure in excess of the yield threshold (P-Y), and the physiological wall extensibility (phi). Three relaxation techniques proved useful: "turgor-relaxation", "balance-pressure" and "pressure-block". In the turgor-relaxation method, water is withheld from growing tissue and the reduction in turgor is measured directly with the pressure probe. This technique give absolute values for P and Y, but requires tissue excision. In the balance pressure technique, the excised growing region is sealed in a pressure chamber, and the subsequent reduction in water potential is measured as the applied pressure needed to return xylem sap to the cut surface. This method is simple, but only measures (P-Y) not the individual values of P and Y. In the pressure block technique, the growing tissue is sealed into a pressure chamber, growth is monitored continuously, and just sufficient pressure is applied to the chamber to block growth. The method gives high-resolution kinetics of relaxation and does not require tissue excision, but only measures (P-Y).The three methods gave similar results when applied to the growing stems of pea (Pisum sativum L.), cucumber (Cucumis sativus L.), soybean (Glycine max (L.) Merr.) and zucchini (Curcubita pepo L.) seedlings. Values for (P-Y) averaged between 1.4 and 2.7 bar, depending on species. Yield thresholds averaged between 1.3 and 3.0 bar. Compared with the other methods, relaxation by pressure-block was faster and exhibited dynamic changes in wall-yielding properties. The two pressure-chamber methods were also used to measure the internal water-potential gradient (between the xylem and the epidermis) which drives water uptake for growth. For the four species it was small, between 0.3 and 0.6 bar, and so did not limit growth substantially. PMID- 24227337 TI - Occurrence of phytoalexins and other putative defense-related substances in uninfected parsley plants. AB - Considerable amounts of the following substances were found in uninfected parsley (Petroselinum crispum) cotyledons: furanocoumarins, the putative phytoalexins of this and some related plant species, two enzymes of the furanocoumarin pathway (S adenosyl-L-methionine: xanthotoxol and S-adenosyl-L-methionine: bergaptol O methyltransferases), two hydrolytic enzymes (1,3-beta-glucanase, EC 3.2.1.39, and chitinase, EC 3.2.1.14), and 'pathogenesis-related' proteins. The furanocoumarins and the methyltransferase activities reached their highest levels at the onset of cotyledon senescence as the hydrolytic enzymes increased from low to relatively high activity values. The relative amounts of pathogenesis-related proteins 1 and 2, as well as the corresponding mRNAs, also increased markedly. Two enzymes of general phenylpropanoid metabolism, L-phenylalanine ammonia-lyase and 4 coumarate: CoA ligase, decreased in activity in a biphasic fashion during cotyledon development. At all developmental stages, the levels of these putative defense-related agents in total cotyledon extracts were too high to enable detection of, possibly, additional changes upon infection with zoospores of Phytophthora megasperma f. sp. glycinea, a fungal pathogen to which parsley shows a non-host, hypersensitive resistance response. PMID- 24227339 TI - Crop management impacts the efficiency of quantitative trait loci (QTL) detection and use: case study of fruit load*QTL interactions. AB - Mapping studies using populations with introgressed marker-defined genomic regions are continuously increasing knowledge about quantitative trait loci (QTL) that correlate with variation in important crop traits. This knowledge is useful for plant breeding, although combining desired traits in one genotype might be complicated by the mode of inheritance and co-localization of QTL with antagonistic effects, and by physiological trade-offs, and feed-back or feed forward mechanisms. Therefore, integrating advances at the genetic level with insight into influences of environment and crop management on crop performance remains difficult. Whereas mapping studies can pinpoint correlations between QTL and phenotypic traits for specific conditions, ignoring or overlooking the importance of environment or crop management can jeopardize the relevance of such assessments. Here, we focus on fruit load (a measure determining competition among fruits on one plant) and its strong modulation of QTL effects on fruit size and composition. Following an integral approach, we show which fruit traits are affected by fruit load, to which underlying processes these traits can be linked, and which processes at lower and higher integration levels are affected by fruit load (and subsequently influence fruit traits). This opinion paper (i) argues that a mechanistic framework to interpret interactions between fruit load and QTL effects is needed, (ii) pleads for consideration of the context of agronomic management when detecting QTL, (iii) makes a case for incorporating interacting factors in the experimental set-up of QTL mapping studies, and (iv) provides recommendations to improve efficiency in QTL detection and use, with particular focus on model-based marker-assisted breeding. PMID- 24227338 TI - A chloroplast-targeted DnaJ protein contributes to maintenance of photosystem II under chilling stress. AB - DnaJ proteins act as essential molecular chaperones in protein homeostasis and protein complex stabilization under stress conditions. The roles of a tomato (Lycopersicon esculentum) chloroplast-targeted DnaJ protein (LeCDJ1), whose expression was upregulated by treatment at 4 and 42 degrees C, and with high light, NaCl, polyethylene glycol, and H2O2, were investigated here using sense and antisense transgenic tomatoes. The sense plants exhibited not only higher chlorophyll content, fresh weight and net photosynthetic rate, but also lower accumulation of reactive oxygen species and membrane damage under chilling stress. Moreover, the maximal photochemistry efficiency of photosystem II (PSII) (F v/F m) and D1 protein content were higher in the sense plants and lower in the antisense plants, and the photoinhibitory quenching was lower in the sense plants and higher in the antisense plants, suggesting that the inhibition of PSII was less severe in the sense plants and more severe in the antisense plants compared with the wild type. Furthermore, the PSII protein complexes were also more stable in the sense plants. Interestingly, the sense plants treated with streptomycin (SM), an inhibitor of organellar translation, still showed higher F v/F m, D1 protein content and PSII stability than the SM-untreated antisense plants. This finding suggested that the protective effect of LeCDJ1 on PSII was, at least partially, independent of D1 protein synthesis. Furthermore, chloroplast heat shock protein 70 was identified as the partner of LeCDJ1. These results indicate that LeCDJ1 has essential functions in maintaining PSII under chilling stress. PMID- 24227341 TI - Distance-dependent quenching of Nile Blue fluorescence byN,N-diethylaniline observed by frequency-domain fluorometry. AB - Fluorescence quenching of Nile Blue by amines is thought to be due to electron transfer to the excited dye molecule from the amine electron donor. We used electron transfer quenching of Nile blue byN,N-diethylaniline in propylene glycol as a model system for an interaction which depends exponentially on distance. We investigated the time dependence of the presumed distance-dependent process using gigahertz harmonic-content frequency-domain fluorometry. The frequency-domain data and the steady-state quantum yield were analyzed globally based on either the Smoluchowski-Collins-Kimball radiation boundary condition (RBC) model or the distancedependent quenching (DDQ) model, in which the rate of quenching depends exponentially on the flourophore-quencher distance. We performed a global analysis which included both the frequencydomain time-resolved decays and the steady-state intensities. The latter were found to be particularly sensitive to the model and parameter values. The data cannot be satisfactorily analyzed using the RBC model for quenching. The analysis shows the excellent agreement of the DDQ model with the experimental data, supporting the applicability of the DDQ model to describe the quenching by the electron transfer process, which depends exponentially on the donor-acceptor distance. PMID- 24227340 TI - Directed evolution of 2G12-targeted nonamannose glycoclusters by SELMA. PMID- 24227342 TI - Invariance of activity coefficients for the hydrogen ion with charge-type of fluorescent indicators in aqueous-methanol solutions. AB - Steady-state fluorimetric pH titrations of three fluorescent indicators of differing charge-type were carried out in aqueous methanol solutions containing up to 64 mol% methanol. The plot of the ratio of the relative fluorescence efficiency of the indicator acid to that of its conjugate base versus the product of the formal hydrogen ion concentration and the appropriate Bronsted kinetic activity factor gives straight lines for titrations in each mixed solvent, just as it does in water, but only if the constant terms in the Bronsted factor are modified to account for the bulk dielectric constant in each solvent. The product of the formal charges on the proton and the particular conjugate base studied in each titration must also be included in the Bronsted factor. This supports the hypothesis that a valid operational pH can be defined and kinetic parameters related to proton transfer can be extracted from the fluorimetric titrations in mixed solvents. PMID- 24227343 TI - Dynamics ofLens culinaris agglutinin studied by red-edge excitation spectra and anisotropy measurements of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) and of tryptophan residues. AB - The fluorescence of 2-p-toluidinylnaphthalene-6-sulfonate bound toLens culinaris agglutinin and of the Trp residues of the protein was investigated. Red-edge excitation spectra and steady-state anisotropy as a function of temperature indicate that the TNS is bound rigidly. Red-edge excitation spectra, steady-state anisotropy as a function of sucrose and anisotropy decay experiments performed on Trp residues fluorescence prove that the internal fluorophore presents residual motion independent of the global rotation of the protein. Fluorescence anisotropy decay allows to calculate the rotational correlation time (351 ps) of this local motion. Quenching resolved emission anisotropy with iodide gives values equal to 0.257 and 0.112 for the anisotropies of the buried and the surface Trp residues, respectively. This result indicates that the Trp residues present at the surface of the protein have important local motions compared to those embedded in the protein matrix. The results obtained from TNS and Trp residues indicate that the agglutinin has different dynamic domains. PMID- 24227344 TI - Spectroscopic and photophysical investigations on the nature of localization of rhodamine-123 and its dibromo derivative in different cell lines. AB - Steady-state and time-resolved spectroscopic properties of rhodamine-123 (rh123) and 4,5-dibromorhodamine methyl ester (dbr123) bound to different cell lines are evaluated. Studies are also performed on the dye bound to extracted mitochondria. Results are compared with those obtained in homogeneous and microheterogeneous media. Results suggest that these dyes can specifically bind only with cell mitochondria. As a result of binding, excitation and emission spectra are red shifted by 10 to 12 nm. The fluorescence decay of these dyes bound to mitochondria shows two lifetimes. Values are about 4.0 and 2.0 ns forrh123 and about 1.9 and 0.5 ns fordbr123. Detailed global analysis of emission wavelength and dye concentration dependences of the fluorescence decay is performed. Results indicate that these dyes are bound to two different binding sites at mitochondria. The decay-associated fluorescence spectrum for the species corresponding to each binding site is recovered. Species1, corresponding to the longer lifetime, is found to be more red shifted compared to species2. The fluorescence of species2 is heavily quenched. The origin of this quenching is explained in terms of resonance energy transfer between donor species2 and acceptor species1. The possible nature of the two binding sites is also discussed. PMID- 24227345 TI - Fluorescence evidence for cholesterol regular distribution in phosphatidylcholine and in sphingomyelin lipid bilayers. AB - Our previous studies indicated that sterols (including cholesterol and dehydroergosterol) can be regularly distributed into hexagonal superlattices in the plane of liquid-crystalline phosphatidylcholine bilayers. It was suggested that regular and irregular regions coexist in the membrane. In the present study, we report supporting evidence for our sterol regular distribution model. We have examined the fractional concentration dependencies of dehydroergosterol (a naturally occurring cholesterol analogue) fluorescence intensity and lifetime in various phosphatidylcholine and sphingomyelin bilayers. Fluorescence intensity and lifetime dips have been observed at specific sterol mole fractions. At those mole fractions, the acrylamide quenching rate constant of dehydroergosterol fluorescence reaches a local maximum. Those mole fractions match the critical sterol mole fractions at which sterol molecules are expected to be regularly distributed into hexagonal superlattices. The results support the idea that the sterols in the regular region are embedded in the bilayer less deep than those in the irregular regions. We have also examined the fractional cholesterol concentration dependencies of diphenylhexatriene (DPH) fluorescence intensity, lifetime, and polarization in DMPC vesicles. DPH fluorescence intensity and polarization also exhibit distinct dips and peaks, respectively, at critical sterol mole fractions for hexagonal superlattices. However, DPH lifetime changes little with sterol mole fraction. As a comparison, the fluorescence properties of DHE and DPH behave differently in response to the formation of sterol regular distribution. Furthermore, finding evidence for sterol regular distribution in both phosphatidylcholine and sphingomyelin membranes raises the possibility that sterol regular distribution may occur within phospholipid/cholesterol enriched domains of real biological membranes. PMID- 24227346 TI - Effect of hydrostatic pressure on the fluorescence of indole derivatives. AB - Effects of hydrostatic pressure on the fluorescence emission of L-tryptophan, N acetyl-L-trytophanamide and indole were investigated. An increase in pressure ranging from 1 bar to 2.4 kbar results in reversible red-shifts of the emission of the three fluorophores. The pressure-induced redshift amounts to about 170 cm( 1) at 2.4 kbar, and appears related to changes in Stokes shift of the fluorophores caused by pressure effects on the dielectric constant and/or refractive index of the medium. As the pressure range investigated here is the range commonly used in studies of protein subunit association and/or folding, these observations raise the need for caution in interpreting pressure-induced spectral shifts. The significance of these observations to pressure studies of proteins is illustrated by investigation of pressure effects on human Cu,Zn Superoxide dismutase (SOD) and azurin fromPseudomonas aeruginosa. A reversible 170 cm(-1) red-shift of the emission of SOD was observed upon pressurization to 2.4 kbar. This might be interpreted as pressure-induced conformational changes of the protein. However, further studies using SOD that had been fully unfolded by guanidine hydrochloride, and fluorescence anisotropy measurements indicated that the observed red-shift was likely due to a direct effect of pressure on the fluorescence of the single tryptophan residue of SOD. Similar pressure-induced red-shifts were also observed for the buried tryptophan residue of azurin or for azurin that had been previously denatured by guanidine hydrochloride. These observations further suggest that the effective dielectric constant of the protein matrix is affected by pressure similarly to water. PMID- 24227347 TI - Cation-sensitive fluorescence of anionic polymers bearing naphtho-18-crown-6 units. AB - Changes in the fluorescence intensity of anionic polymers bearing naphtho-18 crown-6 moieties on addition of cations were studied in water at 30 degrees C. On addition of alkali metal cations, the fluorescence intensity of the polymers decreased sharply for Tl(+) less for Cs(+) and little for Li(+), K(+) and Rb(+). On addition of alkaline earth metal cations, Ba(2+) caused the strongest decrease of the fluorescence intensity of the polymers. The decrease of the fluorescence intensity of the polymers was suggested to be caused by the external heavy-atom effect of the cations bound to the cavity of the crowned naphthalene moiety. The content of the crowned naphthalene units in the polymers affected the cation dependent fluorescence change. The fluorescence change of the polymers based on the cation complexation competition was also studied. PMID- 24227348 TI - Polarized emission from a rhenium metal-ligand complex. AB - We report the first observation of polarized emission from a rhenium phenanthroline complex, Re(CO)3(phen)Cl. Highly luminescent rhenium complexes are known, with quantum yields near 0.5 and lifetimes in excess of 10 MUs. The detection of polarized emission suggests the use of rhenium complexes as probes of the hydrodynamics of large macromolecular complexes and for use in fluorescence polarization immunoassays with gated detection. PMID- 24227349 TI - The effect of cooking on the phytochemical content of vegetables. AB - Cooking induces many chemical and physical modifications in foods; among these the phytochemical content can change. Many authors have studied variations in vegetable nutrients after cooking, and great variability in the data has been reported. In this review more than 100 articles from indexed scientific journals were considered in order to assess the effect of cooking on different phytochemical classes. Changes in phytochemicals upon cooking may result from two opposite phenomena: (1) thermal degradation, which reduces their concentration, and (2) a matrix softening effect, which increases the extractability of phytochemicals, resulting in a higher concentration with respect to the raw material. The final effect of cooking on phytochemical concentration depends on the processing parameters, the structure of food matrix, and the chemical nature of the specific compound. Looking at the different cooking procedures it can be concluded that steaming will ensure better preservation/extraction yield of phenols and glucosinolates than do other cooking methods: steamed tissues are not in direct contact with the cooking material (water or oil) so leaching of soluble compounds into water is minimised and, at the same time, thermal degradation is limited. Carotenoids showed a different behaviour; a positive effect on extraction and the solubilisation of carotenes were reported after severe processing. PMID- 24227350 TI - Surgical aphorisms. PMID- 24227351 TI - Psychological insight for surgeons. PMID- 24227352 TI - Communication in the operating theatre. AB - BACKGROUND: Communication is extremely important to ensure safe and effective clinical practice. A systematic literature review of observational studies addressing communication in the operating theatre was conducted. The focus was on observational studies alone in order to gain an understanding of actual communication practices, rather than what was reported through recollections and interviews. METHODS: A systematic review of the literature for accessible published and grey literature was performed in July 2012. The following information was extracted: year, country, objectives, methods, study design, sample size, healthcare professional focus and main findings. Quality appraisal was conducted using the Critical Appraisal Skills Programme. A meta-ethnographic approach was used to categorize further the main findings under key concepts. RESULTS: Some 1174 citations were retrieved through an electronic database search, reference lists and known literature. Of these, 26 were included for review after application of full-text inclusion and exclusion criteria. The overall quality of the studies was rated as average to good, with 77 per cent of the methodological quality assessment criteria being met. Six key concepts were identified: signs of effective communication, signs of communication problems, effects on teamwork, conditions for communication, effects on patient safety and understanding collaborative work. CONCLUSION: Communication was shown to affect operating theatre practices in all of the studies reviewed. Further detailed observational research is needed to gain a better understanding of how to improve the working environment and patient safety in theatre. PMID- 24227353 TI - Meta-analysis of ischaemic preconditioning for liver resections. AB - BACKGROUND: Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping. METHODS: This was a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating IP in adults undergoing liver resection under either continuous clamping (CC) or intermittent clamping (IC). Primary outcomes were mortality, liver failure and morbidity. Secondary outcomes included duration of operation, blood loss, length of hospital stay, length of intensive therapy unit stay, transfusion requirements, prothrombin time, and bilirubin and aminotransferase levels. Weighted mean differences were calculated for continuous data, and pooled odds ratios (ORs) for dichotomous data. Results were produced with a random effects model with 95 per cent confidence intervals (c.i.). RESULTS: A total of 2960 records were identified and 11 RCTs included 669 patients (IP 331, control 338). No significant difference in mortality (6 RCTs; IP 186, control 190; OR 1.36, 95 per cent c.i. 0.13 to 13.68; P = 0.80) or morbidity (6 RCTs; IP 186, control 190; OR 0.58, 0.31 to 1.07; P = 0.08) was found for IP plus CC versus CC. Nor was there a significant difference in mortality (4 RCTs; IP 122, control 121; OR 1.33, 0.24 to 7.32; P = 0.74) or morbidity (4 RCTs; IP 122, control 121; OR 0.87, 0.52 to 1.47; P = 0.61) for IP plus (CC or IC) versus IC. No significant differences were found for secondary outcome measures. CONCLUSION: This meta analysis failed to find a significant benefit of IP in liver resection. PMID- 24227354 TI - Systematic review and meta-analysis of oesophageal Doppler-guided fluid management in colorectal surgery. AB - BACKGROUND: Oesophageal Doppler monitor (ODM)-guided fluid therapy has been recommended for routine use in patients undergoing colorectal surgery. However, recent trials have suggested either equivalent or inferior results for patients randomized to ODM-guided fluid management, especially when compared with fluid restriction or within the context of optimized perioperative care. Hence, an updated systematic review and meta-analysis was conducted. METHODS: A systematic review and meta-analysis was conducted of all randomized trials exploring ODM guided fluid management in major colorectal surgery with the endpoints total complications and length of hospital stay (LOS). Subset analyses were planned a priori specifically to investigate the role of the ODM in the context of fluid restriction or optimized perioperative care. RESULTS: Six high-quality trials comprising a total of 691 patients were included in the final analysis. ODM guided fluid therapy did not influence the incidence of complications (odds ratio 0.74, 95 per cent confidence interval (c.i.) 0.50 to 1.11; P = 0.15), with moderate heterogeneity in the results (I(2) = 33 per cent; P = 0.19). There was no difference in mean LOS between patients receiving ODM-guided fluid therapy and controls: mean difference -0.88 (95 per cent c.i. -2.89 to 1.13) days (P = 0.39). There was no difference in complications or LOS when ODM-guided fluid therapy was compared with fluid restriction or used within an otherwise optimized perioperative environment. CONCLUSION: ODM-guided fluid therapy did not influence LOS or complications in patients undergoing colorectal surgery. Results favouring the ODM were seen only in early studies, whereas newer trials did not show any benefit from such monitoring. PMID- 24227355 TI - Systematic review and meta-analysis of single-incision versus conventional multiport appendicectomy. AB - BACKGROUND: The aim of this systematic review and meta-analysis was to compare clinical outcomes following single-incision laparoscopic appendicectomy (SILA) and conventional multiport laparoscopic appendicectomy (CLA) for the treatment of acute appendicitis. METHODS: An electronic search of MEDLINE, Embase, Web of Science and Cochrane Library databases was performed. Publications were included if they were clinical trials randomizing patients with appendicitis to SILA or CLA. Outcome measures evaluated included operating time, length of hospital stay, total postoperative complications, and, specifically, wound infection, intra abdominal collection and ileus. Weighted mean difference was calculated for the effect size of SILA on continuous variables, and pooled odds ratios were calculated for discrete variables. RESULTS: The literature search identified seven randomized clinical trials that met the inclusion criteria for meta analysis. In total, 1108 appendicectomies were included, 555 SILA and 553 CLA procedures. There were no significant differences between the groups in the incidence of total postoperative complications, wound infection, intra-abdominal collection, ileus or length of hospital stay. However, SILA was associated with a significantly longer operating time compared with CLA (weighted mean difference 6.96 (95 per cent confidence interval 3.79 to 10.12) min; P < 0.001). Insertion of an additional port was required in 7.6 per cent of patients undergoing SILA. CONCLUSION: SILA is a safe procedure for the treatment of acute appendicitis, with comparable clinical outcome to CLA when undertaken by experienced laparoscopic surgeons. PMID- 24227356 TI - Systematic review of the impact of registration and screening on colorectal cancer incidence and mortality in familial adenomatous polyposis and Lynch syndrome. AB - BACKGROUND: The British Society of Gastroenterology recommends that all familial adenomatous polyposis (FAP) and Lynch syndrome (LS) families are screened in the context of a registry. This systematic review was performed to appraise the published evidence for registration and screening in relation to colorectal cancer (CRC) incidence and mortality. METHODS: Five electronic databases were searched using a combination of medical subject heading terms and free-text keywords. Titles and abstracts were scrutinized by two independent reviewers. Inclusion criteria were English-language studies describing CRC incidence and/or mortality in patients with FAP or LS, with comparison of either: screened and unscreened patients, or time periods before and after establishment of the registry. RESULTS: Of 4668 abstracts identified, 185 full-text articles were selected; 43 studies fulfilled the inclusion criteria. No randomized clinical trial evidence was identified. For FAP, 33 of 33 studies described a significant reduction of CRC incidence and mortality with registration and screening. For LS, nine of ten studies described a reduction of CRC incidence and mortality with registration and screening. Five studies (FAP, 2; LS, 3) provided evidence for complete prevention of CRC-related deaths during surveillance. Clinical and statistical heterogeneity prevented pooling of data for meta-analysis. CONCLUSION: Studies consistently report that registration and screening result in a reduction of CRC incidence and mortality in patients with FAP and LS (level 2a evidence, grade B recommendation). Funding and managerial support for hereditary CRC registries should be made available. PMID- 24227357 TI - Randomized clinical trial of intraoperative superficial cervical plexus block versus incisional local anaesthesia in thyroid and parathyroid surgery. AB - BACKGROUND: Moderate wound pain and opiate analgesia requirement is reported following thyroid and parathyroid surgery. A randomized clinical trial was performed to investigate whether intraoperative superficial cervical plexus block (SCPB) would decrease postoperative pain and analgesia use. METHODS: Patients were randomized to incisional local anaesthesia (control) or incisional local anaesthesia plus intraoperative SCPB. The primary outcome measure was pain, assessed by a visual analogue scale (VAS). Secondary outcome measures were analgesia use (strong opiates defined as having potency at least as strong as that of oral morphine), respiratory rate and sedation score. Primary outcome measures were analysed with non-parametric tests, as well as with receiver operating characteristic (ROC) curves calculated as area under the curve (AUC) to discriminate between trial limbs. RESULTS: Twenty-nine patients were randomized to each group. Pain (VAS) scores were lower in patients who received intraoperative SCPB than in controls 30 min after surgery and subsequently (P < 0.020 at all time points), with a median pain score of zero on the day of operation in the SCPB group. Corresponding analysis of ROC curves showed differences between groups at 30 min (AUC = 0.722, P = 0.012), 90 min (AUC = 0.747, P = 0.005), 150 min (AUC = 0.803, P < 0.001) and 210 min (AUC = 0.849, P < 0.001) after surgery, and at 07.00 hours on postoperative day 1 (AUC = 0.710, P = 0.017). Fewer patients in the SCPB group required strong opiates (5 of 29 versus 16 of 29 in the control group; P = 0.003) and rescue opiates (6 of 29 versus 20 of 29; P < 0.001). CONCLUSION: Intraoperative SCPB reduces pain scores following thyroid and parathyroid surgery, and reduces the requirement for strong and rescue opiates. REGISTRATION NUMBER: 2009-012671-98 (https://www.clinicaltrialsregister.eu). PMID- 24227358 TI - Randomized clinical trial of fluid and salt restriction compared with a controlled liberal regimen in elective gastrointestinal surgery. AB - BACKGROUND: Excessive intravenous fluid prescription may play a causal role in postoperative complications following major gastrointestinal resectional surgery. The aim of this study was to investigate whether fluid and salt restriction would decrease postoperative complications compared with a more modern controlled liberal regimen. METHODS: In this observer-blinded single-site randomized clinical trial consecutive patients undergoing major gastrointestinal resectional surgery were randomized to receive either a liberal control fluid regimen or a restricted fluid and salt regimen. The primary outcome was postoperative complications of grade II and above (moderate to severe). RESULTS: Some 240 patients (194 colorectal resections and 46 oesophagogastric resections) were enrolled in the study; 121 patients were randomized to the restricted regimen and 119 to the control (liberal) regimen. During surgery the control group received a median (interquartile range) fluid volume of 2033 (1576-2500) ml and sodium input of 282 (213-339) mmol, compared with 1000 (690-1500) ml and 142 (93-218) mmol respectively in the restricted group. There was no significant difference in major complication rate between groups (38.0 and 39.0 per cent respectively). Median (range) hospital stay was 8 (3-101) days in the controls and 8 (range 3 76) days among those who received restricted fluids. There were four in-hospital deaths in the control group and two in the restricted group. Substantial differences in weight change, serum sodium, osmolality and urine : serum osmolality ratio were observed between the groups. CONCLUSION: There were no significant differences in major complication rates, length of stay and in hospital deaths when fluid restriction was used compared with a more liberal regimen. REGISTRATION NUMBER: ISRCTN39295230 (http://www.controlled-trials.com). PMID- 24227359 TI - Randomized clinical trial of fluid and salt restriction compared with a controlled liberal regimen in elective gastrointestinal surgery (Br J Surg 2013; 100: 1739-1746). PMID- 24227360 TI - Surgical complications and their implications for surgeons' well-being. AB - BACKGROUND: Healthcare professionals can be seriously affected when they are involved in major clinical incidents. The impact of such incidents on staff is of particular relevance to surgery, as the operating room is one of the highest-risk areas for serious complications. This qualitative study aimed to assess the personal and professional impact of surgical complications on surgeons. METHODS: This single time point study involved semistructured, individual interviews with general and vascular surgeons, consultants and senior registrars from two National Health Service organizations in London, UK. RESULTS: Twenty-seven surgeons participated. Many were seriously affected by major surgical complications. Surgeons' practice was also often affected, not always in the best interest of their patients. The surgeons' reactions depended on the preventability of the complications, their personality and experience, patient outcomes and patients' reactions, as well as colleagues' reactions and the culture of the institution. Discussing complications, deconstructing the incidents and rationalizing were the most commonly quoted coping mechanisms. Institutional support was generally described as inadequate, and the participants often reported the existence of strong institutional blame cultures. Suggestions for supporting surgeons in managing the personal impact of complications included better mentoring, teamwork approaches, blame-free opportunities for the discussion of complications, and structures aimed at the human aspects of complications. CONCLUSION: Those involved in the management of surgical services need to consider how to improve support for surgeons in the aftermath of major surgical incidents. PMID- 24227361 TI - Nomogram for predicting invasion in patients with a preoperative diagnosis of ductal carcinoma in situ of the breast. AB - BACKGROUND: The aim of this study was to identify risk factors for invasive breast cancer in patients diagnosed with ductal carcinoma in situ (DCIS) on a preoperative biopsy. These factors were used to develop a nomogram for predicting the risk of invasion in the preoperative setting. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for DCIS diagnosed before surgery between 1997 and 2009. Multivariable analysis was used to identify clinical, radiological and histopathological factors that may predict upstaging. A nomogram was developed to predict the probability of invasion using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of patients with a preoperative diagnosis of DCIS between 2010 and 2012. RESULTS: Upstaging to invasive cancer occurred in 123 (24.9 per cent) of 493 women treated between 1997 and 2009. A larger DCIS lesion (at least 15 mm), lack of hormone receptor expression, intermediate or high nuclear grade, diagnosis on core biopsy compared with vacuum-assisted biopsy, and non-cribriform subtype of DCIS were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic (ROC) curve (AUC) 0.823, 95 per cent confidence interval 0.787 to 0.860). The nomogram showed similar predictive performance in the validation data set, based on another 149 women (AUC 0.700, 0.613 to 0.786). CONCLUSION: Upstaging to invasive cancer in women with a preoperative diagnosis of DCIS is common. A nomogram based on the five most significant factors related to upstaging accurately predicted invasive cancer. This nomogram may be useful when deciding whether to pursue axillary staging with sentinel lymph node biopsy in patients with DCIS. PMID- 24227362 TI - Vascular reconstruction combined with liver resection for malignant tumours. AB - BACKGROUND: The resectability criteria for malignant liver tumours have expanded during the past two decades. The use of vascular reconstruction after hepatectomy has been integral in this process. However, the majority of reports are anecdotal. This is a retrospective analysis of the techniques, morbidity, mortality and risk factors of liver resections with vascular reconstruction based on a large series from a single centre. METHODS: Patients who underwent hepatic resection combined with vascular resection and reconstruction between 1997 and 2009 were included in this study. Indications for surgery, morbidity and 90-day mortality are reported along with factors predictive of operative mortality. RESULTS: Eighty-four patients had liver resection with 97 vascular resections and reconstruction. There were 44 men and 40 women with a mean(s.d.) age of 56.9(12.1) years. Mean(s.d.) follow-up was 37.3(34.1) months. All patients had primary or metastatic liver tumours. The perioperative morbidity rate was 62 per cent (52 patients) and the operative mortality rate 14 per cent (12). Predictors of operative mortality were: bilirubin level exceeding 34 umol/ml (P = 0.023), indocyanine green retention rate at 15 min over 10 per cent (P = 0.031), duration of ischaemia (P = 0.011), amount of blood transfused (P = 0.025) and combined major extrahepatic procedure (P = 0.042). Actuarial 3- and 5-year survival rates were 44 and 26 per cent respectively. CONCLUSION: Liver resection with combined vascular resection and reconstruction can be performed in selected patients with acceptable morbidity and mortality. The lack of therapeutic alternatives and the poor outcome of non-operative management seem to justify this approach. The identification of risk factors should help improve patient selection and postoperative outcome as well as facilitate objective risk communication with surgical candidates. PMID- 24227363 TI - Vascular reconstruction combined with liver resection for malignant tumours (Br J Surg 2013; 100: 1764-1775). PMID- 24227364 TI - Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival. AB - BACKGROUND: Most patients requiring an extended right hepatectomy (ERH) have an inadequate standardized future liver remnant (sFLR) and need preoperative portal vein embolization (PVE). However, the clinical and oncological impact of PVE in such patients remains unclear. METHODS: All consecutive patients presenting at the M. D. Anderson Cancer Center with colorectal liver metastases (CLM) requiring ERH at presentation from 1995 to 2012 were studied. Surgical and oncological outcomes were compared between patients with adequate and inadequate sFLRs at presentation. RESULTS: Of the 265 patients requiring ERH, 126 (47.5 per cent) had an adequate sFLR at presentation, of whom 123 underwent a curative resection. Of the 139 patients (52.5 per cent) who had an inadequate sFLR and underwent PVE, 87 (62.6 per cent) had a curative resection. Thus, the curative resection rate was increased from 46.4 per cent (123 of 265) at baseline to 79.2 per cent (210 of 265) following PVE. Among patients who underwent ERH, major complication and 90 day mortality rates were similar in the no-PVE and PVE groups (22.0 and 4.1 per cent versus 31 and 7 per cent respectively); overall and disease-free survival rates were also similar in these two groups. Of patients with an inadequate sFLR at presentation, those who underwent ERH had a significantly better median overall survival (50.2 months) than patients who had non-curative surgery (21.3 months) or did not undergo surgery (24.7 months) (P = 0.002). CONCLUSION: PVE enabled curative resection in two-thirds of patients with CLM who had an inadequate sFLR and were unable to tolerate ERH at presentation. Patients who underwent curative resection after PVE had overall and disease-free survival rates equivalent to those of patients who did not need PVE. PMID- 24227365 TI - Postoperative adverse outcomes after non-hepatic surgery in patients with liver cirrhosis. AB - BACKGROUND: Postoperative adverse outcomes in patients with liver cirrhosis are not completely understood. This study evaluated the association between liver cirrhosis and adverse outcomes after non-hepatic surgery. METHODS: Reimbursement claims were used to identify patients with preoperative liver cirrhosis who underwent non-hepatic surgery from 2004 to 2007. Control patients without cirrhosis were matched by age, sex, type of surgery and anaesthesia. The adjusted odds ratios (ORs) and 95 per cent confidence intervals (c.i.) of postoperative adverse events associated with liver cirrhosis were analysed by multivariable logistic regression. RESULTS: Thirty-day mortality rates among 24 282 patients with cirrhosis and 97 128 control patients were 1.2 per cent (299 deaths) and 0.7 per cent (635 deaths) respectively. Liver cirrhosis was associated with postoperative 30-day mortality (OR 1.88, 95 per cent c.i. 1.63 to 2.16), acute renal failure (OR 1.52, 1.34 to 1.74), septicaemia (OR 1.42, 1.33 to 1.51) and intensive care unit admission (OR 1.39, 1.33 to 1.45). Postoperative mortality increased in patients who had liver cirrhosis with viral hepatitis (OR 2.87, 1.55 to 5.30), alcohol dependence syndrome (OR 3.74, 2.64 to 5.31), jaundice (OR 5.47, 3.77 to 7.93), ascites (OR 5.85, 4.62 to 7.41), gastrointestinal haemorrhage (OR 3.01, 2.33 to 3.90) and hepatic coma (OR 5.11, 3.79 to 6.87). CONCLUSION: Patients with liver cirrhosis had increased mortality and complications after non hepatic surgery, particularly those with cirrhosis-related clinical indicators. PMID- 24227366 TI - Value of peritoneal cytology in potentially resectable pancreatic cancer. AB - BACKGROUND: Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. METHODS: Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. RESULTS: Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0.005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0.030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY- tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY- tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15.3 versus 10.0 months; P = 0.057). CONCLUSION: CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status. PMID- 24227367 TI - Altered central pain processing after pancreatic surgery for chronic pancreatitis. AB - BACKGROUND: Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. METHODS: Patients with CP underwent quantitative sensory testing. Pain processing was measured via electrical pain detection (ePDT) and electrical pain tolerance (ePTT) thresholds in dermatomes C5 and L4. Inhibitory descending pain control mechanisms were assessed using the conditioned pain modulation (CPM) paradigm. Healthy controls and patients with CP were compared, and patients with CP and a poor pain outcome (visual analogue scale (VAS) score greater than 30) were compared with those with a good pain outcome (VAS score 30 or less). RESULTS: Forty-eight patients with CP had lower ePDT, ePTT and CPM responses compared with values in 15 healthy controls (P < 0.030). The sum of ePDT values was lower in patients with a poor pain outcome than in those with a good outcome (median 7.1 versus 11.2 mA; P = 0.008). There was a correlation with the VAS score and the sum of ePDT values (rs = -0.45, P = 0.016) and ePTT values (rs = -0.46, P = 0.011), and CPM response (rs = -0.43, P = 0.006) in patients with CP. CONCLUSION: After pain-relieving pancreatic surgery, patients with CP exhibit altered central pain processing compared with that in healthy controls. Poor pain outcomes are associated with more central sensitization and more pronociceptive descending pain modulation, and this should be considered when managing persistent pain after pain-relieving surgery for CP. PMID- 24227368 TI - Local recurrence after stenting for obstructing left-sided colonic cancer. AB - BACKGROUND: Self-expanding metallic stents (SEMS) may be used in acute obstructing left-sided colonic cancers to avoid high-risk emergency surgery. However, oncological safety remains uncertain. This study evaluated the long-term oncological outcome of SEMS as a bridge to elective curative surgery versus emergency resection. METHODS: A consecutive prospective cohort of patients admitted with obstructing left-sided colonic cancer between 2006 and 2012 was analysed. The decision to stent as a bridge to surgery or to perform emergency surgery was made by the on-call consultant colorectal surgeon in conjunction with a consultant interventional radiologist; when appropriate, they performed the stent procedure together. Primary outcomes were local and distant recurrence, and overall survival. Secondary outcomes were postoperative complications, in hospital mortality, proportion of procedures undertaken laparoscopically, and anastomosis and stoma rates. RESULTS: In total, 105 patients with obstructing left-sided colonic cancer were treated with curative intent; 62 were treated with SEMS as a bridge to surgery and 43 had emergency resection. In patients aged 75 years or less, stenting and delayed surgery was associated with a higher local recurrence rate compared with emergency surgery at the end of follow-up (32 versus 8 per cent; P = 0.038). This did not translate into a significant difference in overall survival. CONCLUSION: SEMS was associated with an increased local recurrence rate. PMID- 24227369 TI - Population-based cohort study comparing 30- and 90-day institutional mortality rates after colorectal surgery. AB - BACKGROUND: Surgical mortality results are increasingly being reported and published in the public domain as indicators of surgical quality. This study examined how mortality outlier status at 90 days after colorectal surgery compares with mortality at 30 days and subsequent intervals in the first year after surgery. METHODS: All adults undergoing elective and emergency colorectal resection between April 2001 and February 2007 in English National Health Service (NHS) Trusts were identified from administrative data. Funnel plots of postoperative case mix-adjusted institutional mortality rate against caseload were created for 30, 90, 180 and 365 days. High- or low-mortality unit status of individual Trusts was defined as breaching upper or lower third standard deviation confidence limits on the funnel plot for 90-day mortality. RESULTS: A total of 171 688 patients from 153 NHS Trusts were included. Some 14 537 (8.5 per cent) died within 30 days of surgery, 19 466 (11.3 per cent) within 90 days, 23 942 (13.9 per cent) within 180 days and 31 782 (18.5 per cent) within 365 days. Eight institutions were identified as high-mortality units, including all four units with high outlying status at 30 days. Twelve units were low-mortality units, of which six were also low outliers at 30 days. Ninety-day mortality correlated strongly with later mortality results (rs = 0.957, P < 0.001 versus 180-day mortality; rs = 0.860, P < 0.001 versus 365-day mortality). CONCLUSION: Extending mortality reporting to 90 days identifies a greater number of mortality outliers when compared with the 30-day death rate. Ninety-day mortality is proposed as the preferred indicator of perioperative outcome for local analysis and public reporting. PMID- 24227370 TI - Risk of infection and sepsis in severely injured patients related to single nucleotide polymorphisms in the lectin pathway. AB - BACKGROUND: Infectious complications remain a serious threat to patients with multiple trauma. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess whether single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients. METHODS: A prospective cohort of severely injured patients admitted to a level I trauma centre between January 2008 and April 2011 were genotyped for SNPs in MBL2 (mannose-binding lectin 2), MASP2 (MBL-associated serine protease 2) and FCN2 (ficolin 2). Association of genotype with prevalence of positive culture findings and infection was tested by chi(2) and logistic regression analysis. RESULTS: A total of 219 patients were included, of whom 112 (51.1 per cent) developed a positive culture from sputum, wounds, blood or urine. A systemic inflammatory response syndrome (SIRS) developed in 139 patients (63.5 per cent), sepsis in 79 (36.1 per cent) and septic shock in 37 (16.9 per cent). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (odds ratio (OR) 2.51, 95 per cent confidence interval 1.12 to 5.62; P = 0.025). A MASP2 Y371D DD genotype predisposed to SIRS (OR 4.78, 1.06 to 21.59; P = 0.042) and septic shock (OR 2.53, 1.12 to 4.33; P = 0.003). A FCN2 A258S AS genotype predisposed to positive wound cultures (OR 3.37, 1.45 to 7.85; P = 0.005) and septic shock (OR 2.18, 1.30 to 4.78; P = 0.011). CONCLUSION: Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings, and to infectious complications, SIRS and septic shock than patients with a wildtype genotype. PMID- 24227372 TI - Outcomes following prosthetic patch repair in newborns with congenital diaphragmatic hernia. AB - BACKGROUND: The anatomical defect in congenital diaphragmatic hernia (CDH) can usually be closed primarily but prosthetic patch repair may be required in newborns with a deficient diaphragm. High rates of patch failure and hernia recurrence (up to 50 per cent) have been reported. This study evaluated contemporary outcomes following patch repair of CDH at a UK paediatric surgical centre. METHODS: Medical records of newborns undergoing surgery for CDH between 1 February 1990 and 1 November 2010, and attending a multidisciplinary follow-up clinic, were examined. Operative details and patch utilization are reported. RESULTS: Of 118 newborns with CDH, 37 required a patch to the diaphragmatic defect. Gore-Tex(r) patches were used in 35 and biological Surgisis(r) patches in two. Eight babies additionally required an abdominal wall patch. Seven infants had an abdominal patch alone with primary diaphragm repair. A total of 102 infants (86.4 per cent) survived after surgery. Two early recurrences were both related to the use of biological patches, leading to revisional surgery with Gore Tex(r) patch reconstruction. Diaphragmatic patch use was associated with a greater requirement for intensive cardiovascular and respiratory support, although there was no significant difference in mortality between patch versus primary diaphragm repair. The mortality rate was significantly higher among infants requiring abdominal wall patching (with or without a diaphragmatic patch): 40 per cent (6 of 15) versus 9.7 per cent (10 of 103) (P = 0.006). Postoperative survival rates for infants with a diaphragmatic patch alone, abdominal wall patch alone, and both abdominal and diaphragmatic patches were 86 per cent (25 of 29), 57 per cent (4 of 7) and 63 per cent (5 of 8) respectively. CONCLUSION: Prosthetic diaphragmatic hernia repair at this centre has a good outcome and low rate of recurrence (5 per cent). The recognition of an inadequate abdominal domain prenatally may additionally prove to be a useful marker for predicting increased mortality in newborns with CDH. PMID- 24227371 TI - Population-based study of presentation and adverse outcomes after femoral hernia surgery. AB - BACKGROUND: Rates of emergency admission with femoral hernia are high compared with those for other hernias. This study aimed to determine the modes and consequences of presentation to primary care before admission to hospital. METHODS: This was a population-based cohort study using healthcare records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from 1997 to 2007. Length of hospital stay, bowel resection rates and 30-day mortality were calculated. RESULTS: A total of 885 patients (690 female, 78.0 per cent) underwent femoral hernia repair, with 406 operations (45.9 per cent) performed as an emergency. The majority of patients who were admitted as an emergency (331, 81.5 per cent) presented to the general practitioner for the first time with symptoms of a hernia in the 7 days before admission, compared with just ten (2.1 per cent) of 479 patients admitted electively (P < 0.001). The median (i.q.r.) length of stay for patients undergoing elective surgery was 1 (0 2) day compared with 5 (3-9) days for those having an emergency repair (P < 0.001). Adverse events were more common among patients operated on as emergency, with 94 (23.2 per cent) having a small bowel resection compared with one (0.2 per cent) who had elective surgery. There were no deaths within 30 days in the elective group, but seven (1.7 per cent) in the emergency group. CONCLUSION: A large proportion of patients with femoral hernia present late to primary care and are operated on as an emergency, with worse outcomes. PMID- 24227373 TI - Authors' reply: systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication (Br J Surg 2012; 99: 1630-1638). PMID- 24227374 TI - Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication (Br J Surg 2012; 99: 1630-1638). PMID- 24227376 TI - Superoxide dismutase activity of the naturally occurring human serum albumin copper complex without hydroxyl radical formation. AB - The superoxide radical anion (O2(.-)) is biologically toxic and contributes to the pathogenesis of various diseases. Here we describe the superoxide dismutase (SOD) activity of human serum albumin (HSA) complexed with a single Cu(II) ion at the N-terminal end (HSA-Cu complex). The structure of this naturally occurring copper-coordinated blood serum protein has been characterized by several physicochemical measurements. The O2(.-) dismutation ability of the HSA-Cu (1:1) complex is almost the same as that of the well-known SOD mimics, such as Mn(III) tetrakis(N-methylpyridinium)porphyrin. Interestingly, the HSA-Cu complex does not induce a subsequent Fenton reaction to produce the hydroxyl radical (OH(.)), which is one of the most harmful reactive oxygen species. PMID- 24227377 TI - A systematic large-scale phenotypic analysis of de novo and inherited copy number variation. PMID- 24227378 TI - Field performance of woodburning stoves in crested butte, Colorado. AB - The carbon monoxide (CO) and particulate matter (PM) emissions of woodburning stoves have been measured under field conditions. Both conventional airtight stoves and newly installed airtight stoves certified by the U.S. Environmental Protection Agency to be low emitters of PM were monitored. The certified stoves were of two types, catalytic and noncatalytic. Compared to the conventional stoves, PM emission rates (g/hr) were reduced approximately 70% by both types of certified stoves. The CO emission rates were reduced 71% and 53% by catalytic and noncatalytic stoves respectively. These rate reductions occur because the certified stoves burn cleaner (less pollutant formation per kg of wood burned) and the average burn rate of certified stoves in field use is less than the average burn rate of conventional stoves. PMID- 24227379 TI - Effect of contaminated groundwater on tree growth: A tree-ring analysis. AB - A study was conducted of the effect of contaminated groundwater seepage on tree growth downslope from the F- and H-Area seepage basins of the Department of Energy's Savannah River Site in South Carolina. Trees in wetlands along Four Mile Creek began to show localized stress and mortality in the late 1970s. Extreme winter temperatures and high rainfall were ruled out as potential causal factors of tree stress. Drought was shown to affect trees in both contaminated and uncontaminated zones, but trees in uncontaminated areas exhibited better recovery after drought than trees in contaminated areas. Pollution-mediated alteration of soil acidity and aluminum, sodium, and heavy metal concentrations likely acted to predispose trees to decline, with severe drought acting as the trigger for decline initiation and tree death. Thus, a moderate pollution loading, not sufficient to cause visible damage of itself, may create conditions in which sudden, severe decline could result from natural stresses. This mechanism of forest decline may be common, and should be considered in evaluations of the impact of pollution on wetland forest systems. PMID- 24227380 TI - Evaluation of sampling strategies to characterize dissolved oxygen conditions in northern Gulf of Mexico estuaries. AB - Dissolved oxygen was continuously monitored in eight sites of northern Gulf of Mexico estuaries in August, 1990. Monte Carlo analyses on subsamples of the data were used to evaluate several commonly used monitoring strategies. Monitoring strategies which involve single point sampling of dissolved oxygen may often misclassify an estuary as having good water quality. In the case of shallow, often well-mixed estuaries that experience diurnal cycles, such monitoring often does not occur at night, during the time of lowest dissolved oxygen concentration. Our objective was to determine the minimum sampling effort required to correctly classify a site in terms of the observed frequency of hypoxia. Tests concluded that the most successful classification strategy used the minimum dissolved oxygen concentration from a continuously sampled 24-hour period. PMID- 24227381 TI - Remote measurement of NO2 in the brown cloud over Albuquerque, New Mexico. AB - Remote measurements of nitrogen dioxide (NO2) were recorded in the 'brown cloud' over Albuquerque, NM, using absorption spectroscopy in the winter of 1987-88 and summer of 1989. The NO2 burdens (optical densities) measured in this manner were found to be in excess of 100 ppm-m. These long pathlength measurements correspond to total concentrations of approximately 5-10 ppb over the integrated observation pathlengths, which ranged from 10-20 km. These concentrations compare well with single location, independent NO x analyses. Using two correlation (absorption) spectrometers simultaneously, it was shown that the NO2 distribution is not uniform over the city and can change on the order of minutes in the boundary layer late in the day, demonstrating the advantages of NO2 optical measurements for assessing the location and extent of urban nitrogen dioxide levels in the boundary layer. PMID- 24227382 TI - Tilapia cage culture and the dissolved oxygen trends in Sampaloc Lake, the Philippines. AB - The 28-hectare tilapia cage culture that occupied the 104-hectare Sampaloc Lake, a crater lake, shifted to intensive method in 1986 when tilapia growth slowed done at the beginning of 1982. Thus, commercial feeds became the main source of allochthonous organic matter in the lake. Total feeds given annually for the 28 hectare cage culture at 3 croppings per year amounted to 5250 tons. At feed conversion ratio of 1 : 2 a significant portion of the feeds given ended as organic wastes in the lake. In 1988, tilapia cage operators began experiencing their worst occurrences of fishkill, worth millions of pesos. An assessment of the dissolved oxygen condition of Sampaloc lake in late 1989, 1990 and mid-1991 showed ominous trends which might adversely affect the use of Sampaloc lake for fishery. PMID- 24227383 TI - Comparative rice seed toxicity tests using filter paper, growth pouch-tm, and seed tray methods. AB - Paper substrate, especially circular filter paper placed inside a Petri dish, has long been used for the plant seed toxicity test (PSTT). Although this method is simple and inexpensive, recent evidence indicates that it gives results that are significantly different from those obtained using a method that does not involve paper, especially when testing metal cations. The study compared PSTT using three methods: filter paper, Growth Pouch-TM, and seed tray. The Growth Pouch-TM is a commercially available device. The seed tray is a newly designed plastic receptacle placed inside a Petri dish. The results of the Growth Pouch-TM method showed no toxic effects on rice for Ag up to 40 mg L(-1) and Cd up to 20 mg L( 1). Using the seed tray method, IC50 (50% inhibitory effect concentration) values were 0.55 and 1.4 mg L(-1) for Ag and Cd, respectively. Although results of filter paper and seed tray methods were nearly identical for NaF, Cr(VI), and phenol, the toxicities of cations Ag and Cd were reduced by using the filter paper method; IC50 values were 22 and 18 mg L(-1), respectively. The results clearly indicate that paper substrate is not advisable for PSTT. PMID- 24227384 TI - Trace monitoring of water-borne phenolics in the Klang River Basin. AB - The Klang River Basin is located in the most densely populated region in Malaysia, with its heavy concentration of industries and population. A systematic study of the pollution to this river system caused by phenolic compounds have been carried out under this project. Analyses of water samples from the Klang River by high performance liquid chromatography (HPLC) with an ultraviolet (UV) detector at 280 nm have shown the presence of some priority phenolic pollutants. PMID- 24227385 TI - Editor's note. PMID- 24227386 TI - On perhaps becoming what you had previously despised: Psychologists as prescribers of medication. AB - The authors contend that organized psychology's efforts to gain limited prescriptive privileges may be misguided. The modification of psychology's traditional scope of practice may produce harm in the form of lessened patient regard, devaluation of nonpharmacologic elements of practice, and markedly increased exposure to claims of malpractice. The authors also decry the disingenuous use of psychopharmacologically "underserved" populations as rationales for the pursuit of prescriptive privileges. Psychology may mount a major effort to make this change without sufficient justification, in the view of the authors. PMID- 24227387 TI - Prescription privileges and psychology: A reply to adams and Bieliauskas. AB - The ability to prescribe psychoactive medications is a legitimate extension of the practice of psychology. Arguments raised against this proposition by Adams and Bieliauskas should not deter the profession from attaining prescriptive authority. Prescription privileges will expand the range of disorders and patient populations that psychologists can treat. Their acquisition will be of benefit to both the profession and the patient alike. PMID- 24227388 TI - Could versus should: A reply to Sammons. AB - Sammons (1994) believes that our critique of organized psychology's efforts to gain limited prescriptive privileges (Adams & Bieliauskas, 1994) is comprised of pseudo-problems (e.g., the noncurative nature of psychopharmacology) or issues that can readily be handled (e.g., malpractice exposure). We disagree and attempt herein to inject some reality into the picture of the bright new world of psychologists armed with prescription pads. Most importantly, the seemingly vanished distinction between whatcould be done politically or legislatively and whatshould be done for the profession and the public good is redrawn. PMID- 24227389 TI - Training program in psychosocial intervention for high-risk infants and their families. AB - A multidisciplinary training program for psychosocial intervention in the Neonatal Intensive Care Unit (NICU) was developed. The purpose of the program was to train mental health and health care professionals in a psychosocial preventive intervention model for high-risk infants and their families throughout the infants' hospital course in the NICU. The program was divided into modules that include assessment and intervention with the infant, parents, family, and larger caregiving environment. Over a 3-year period 40 trainees from 9 disciplines were trained. A randomized clinical trial was conducted which showed the positive effects of the intervention. A clinical service including inpatient and outpatient follow-up has been established in the NICU based on the psychosocial model developed from the training program. PMID- 24227390 TI - Caregivers of adults with cancer: Multidimensional correlates of psychological distress. AB - The relationship between psychological distress and intrapersonal, family, and socioecological variables was examined in 77 caregivers of adults actively receiving cancer treatment. Results indicated that a sizable minority (29%) of caregivers was experiencing clinically significant psychological distress. Furthermore, family disturbances and maladaptive coping strategies were most predictive of psychological distress in this sample. The clinical implications of these findings in relation to the assessment and treatment of both patients and caregivers are discussed. PMID- 24227391 TI - Meta-monitoring: Case illustrations of a potential "Slump-Buster" for self regulatory problems. AB - Meta-monitoring has been defined as a secondary feedback system in which people monitor their rates of progress in attaining their primary self-regulatory goals. The purpose of this study was to explore the effects of adding an explicit version of meta-monitoring to a long-term cognitive-behavioral treatment program for obesity. It was expected that meta-monitoring in this therapeutic context might increase positive affect and, thereby, improve self-regulated cognitive and behavioral changes. Four obese women who were in treatment for 1 to 2 years prior to the study served as subjects. They meta-monitored by rating their self monitoring, affect, and eating and thinking patterns for each of 34 weeks. Weight changes and measures of self-monitoring, affect, and eating/thinking patterns suggested some initially positive effects (during the first 2 weeks, especially). While the duration of the impact of meta-monitoring in this clinical trial seemed modest, the approach may have promise as a means of reenergizing self-regulatory efforts during lapses or slumps. Experiments on various methods of operationalizing meta-monitoring, examining its effects on different problems, and testing its hypothesized mechanisms seem warranted. PMID- 24227392 TI - Measuring depressive symptomatology of patients referred to a behavioral medicine clinic: Concordance of self-report measures. AB - We measured depressive symptomatology of 134 outpatient veterans treated within a Behavioral Medicine Clinic utilizing three reliable instruments with depression subscales: Minnesota Multiphasic Personality Inventory (MMPI), Derogatis Stress Profile (DSP), and Symptom Checklist 90-Revised (SCL-90-R). Results indicate that although the instruments correlate significantly, they differ in sensitivity to depression and are clinically discordant. The MMPI classified a substantially higher number of patients as depressed than either the DSP or SCL-90-R. The present study argues that the discrepancy in clinical concordance and sensitivity of the three depression scales has considerable implications for psychologists concerned with the assessment and treatment of depression. PMID- 24227393 TI - The clinical utility of the Rey Auditory-Verbal Learning Test in medical rehabilitation. AB - Recent research has reported the Rey Auditory-Verbal Learning Test Trial V (RAVLT V) score to be a sensitive indicator of global cognitive functioning, not merely verbal learning skills. The concurrent validity of the RAVLT-V relative to other neuropsychological measures frequently utilized in medical rehabilitation was investigated in a sample of 64 outpatients diagnosed with traumatic brain injury (TBI). The sample was predominantly male (77%), white (97%), youthful (31.4+/ 11.5 years), high school educated, and an average of 53 months postinjury. Using stepwise multiple regression analysis, a three-variable model consisting of gender, Wechsler Memory Scale-Revised Delayed Memory Index, and Trailmaking Part B (time) accounted for 61% of the variance in RAVLT-V scores. These findings suggest that in TBI patients, the RAVLT taps not only specific verbal learning and memory, but also global cognitive functions. Sensitivity to diffuse neuropsychological changes and ease/speed of administration make the RAVLT a valuable tool in medical rehabilitation settings. PMID- 24227394 TI - Self-appraised problem-solving skills and the prediction of secondary complications among persons with spinal cord injuries. AB - Secondary complications following spinal cord injury (SCI) include decubitus ulcers and recurrent urinary tract infections. These conditions can significantly impair quality of life and prove life-threatening; it is also believed that these conditions are mediated by behavioral pathways. According to the social problem solving model, persons who report effective problem-solving skills should be capable of adhering to long-term therapeutic regimens of self-care necessary to prevent these complications. We tested this assumption in the present study. Discriminant function analyses revealed self-appraised skills in approaching and defining problems contributed to the prediction of secondary complications among 53 persons with SCI. Results are discussed in light of the social problem-solving model, and the utility of problem-solving interventions in rehabilitation is explored. PMID- 24227395 TI - A metal-free multicomponent cascade reaction for the regiospecific synthesis of 1,5-disubstituted 1,2,3-triazoles. PMID- 24227396 TI - Medial patellofemoral ligament (MPFL) reconstruction for the treatment of patellofemoral instability. AB - Patellofemoral instability can be a disabling problem. Numerous techniques are employed for its treatment. Medial patellofemoral ligament (MPFL) reconstruction in combination with other procedures has been explored by many orthopedic surgeons. The purpose of the study was to determine the effectiveness of isolated MPFL reconstruction in treating the symptoms associated with patellofemoral instability, preventing recurrence of patella dislocation, and returning patients to preinjury level of activity. This is a case series study. We conducted a clinical follow-up study on 56 knees (49 patients) after MPFL reconstruction for recurrent patellar instability with a mean follow-up of 4.3 years (range, 1.1 6.8). A single MPFL reconstruction technique was performed in all cases. Patient outcomes were evaluated using: International Knee Documentation Committee (IKDC) subjective knee form, Tegner activity score, functional hop test, and radiographs. Mean age at time of surgery was 24 years old (range, 13-49). Females comprised 75% of the sample. Mean interval from injury to surgery was 7.2 +/- 8.6 years (range, 51 days-37 years). At follow-up, there were no recurrent dislocations reported, patella subluxation in 6 (11%) cases, and radiographic degenerative changes were none to mild in all patients. The series mean IKDC scores at follow-up was 76.3 +/- 19.2 (range, 30-99), and Tegner activity scores were 5.6 +/- 2.5. MPFL reconstruction is an option for treating the symptoms of patellar instability, preventing recurrent dislocation, and returning patients near to their preinjury level of activity. The level of evidence is IV. PMID- 24227397 TI - Anterior horn lateral meniscus tear, repair, and meniscectomy. AB - The purpose of this study was to describe the effect of anterior horn of the lateral meniscus (AHLM) tears on tibiofemoral contact pressures and the ability to restore normal parameters with repair. Eight fresh-frozen cadaveric knees were used. The specimens were subjected to a load of 1,000 N at 0 and 30 degrees of flexion and peak pressure, force and contact area were recorded. The test was repeated for four different instances. Peak force in the lateral compartment was significantly increased at 0 degrees of knee flexion from 37 N intact to 47 N after the tear and 56 N postmeniscectomy. At 0 degrees of knee flexion, the peak pressure of the lateral meniscus was significantly increased from 1.1 MPa in the intact state to 1.9 MPa after meniscectomy. The peak pressure in the nontraumatized medial compartment was significantly increased after partial lateral meniscectomy (p < 0.05). This cadaveric study demonstrated a significant increase in tibiofemoral peak forces in both the medial and lateral compartments with a tear of the AHLM. It also showed an increase in peak contact pressure after meniscectomy. With repair, the preinjury condition peak forces were restored to normal, suggesting the importance of repairing tears of the AHLM. PMID- 24227398 TI - A new simplified onlay technique for posterior cruciate ligament reconstruction. AB - The integrity of posterior cruciate ligament (PCL) is essential for the normal kinematics of the knee. Injury to the PCL has adverse consequences, with worsening of functional performance and an increased risk to develop osteoarthritis. Conservative treatment is sometimes adopted, not only because it is an acceptable option for selected patients but also due to the lack of consensus in the orthopedic literature regarding the best surgical method. Hereby we describe a simplified technique for onlay PCL reconstruction pointing out possible advantages if compared with the traditional transtibial or inlay techniques. PMID- 24227399 TI - Time to get rid of the clock: intraobserver and interobserver reliability in determination of the o'clock position of the femoral tunnel in ACL reconstruction. AB - This study evaluates intraobserver and interobserver agreement in reporting the o'clock position of the femoral tunnel during anterior cruciate ligament (ACL) reconstruction. Four PGY2 residents, four PGY5 residents, and four sports medicine orthopedic surgeons reported the o'clock position of the femoral ACL tunnel in 10 arthroscopic pictures on two occasions 3 months apart. Intraobserver agreement was determined using the intraobserver correlation coefficient (r > 0.576 for 0.05 significance level). Interobserver agreement between members of each group and between reviewer groups was evaluated with the intraclass correlation coefficient (ICC > 0.75 considered good agreement). Poor interobserver agreement was demonstrated between the attending and PGY2 groups (ICC = 0.1685), between the attending and PGY5 groups (ICC = 0.2982), and between the PGY5 and PGY2 groups (ICC = 0.267). Attending surgeons, PGY5s, and PGY2s demonstrated poor interobserver agreement amongst themselves (ICC = 0.2244, 0.471, and 0.0859, respectively). PGY2s and PGY5s demonstrated good intraobserver agreement, but attending surgeons demonstrated poor intraobserver agreement. Attending orthopedic surgeons and residents of different levels of training interpret the o'clock position of the femoral tunnel differently. Greater years of experience does not improve intraobserver or interobserver agreement on the o'clock position. The clock face terminology for femoral tunnel placement may not be a reliable descriptor for scientific investigations or clinical instruction. PMID- 24227400 TI - Comparison of robot surgery modular and total knee arthroplasty kinematics. AB - The kinematics of seven knee specimens were measured from 0 to 120 degrees flexion using an up-and-down crouching machine. Motion was characterized by the positions of the centers of the lateral and medial femoral condyles in the anterior-posterior direction relative to a fixed tibia. A modular unicompartmental knee, trochlea flange, and patella resurfacing (multicompartmental knee [MCK] system) were implanted using a surgeon-interactive robot system that provided accurate surface matching. The MCK was tested, followed by standard cruciate retaining (CR) and posterior stabilized (PS) knees. The motion of the MCK was close to anatomic, especially on the medial side, in contrast to the CR and PS knees that showed abnormal motion features. Such a modular knee system, accurately inserted, has the potential for close to normal function in clinical application. PMID- 24227401 TI - Contrasting reactions of loggerhead shrikes to two types of chemically defended insect prey. AB - Feeding tests with loggerhead shrikes (Lanius ludovicianus) showed this bird to acceptUtetheisa ornatrix, a moth (Arctiidae) protected by pyrrolizidine alkaloids, but to avoidLytta polita, a beetle (Meloidae) containing cantharidin. PMID- 24227402 TI - Influence of snail feces and mucus on oviposition and larval behavior ofPherbellia cinerella (Diptera: Sciomyzidae). AB - Larvae of the sciomyzid flyPherbellia cinerella are voracious predators of terrestrial helicid snails. Eggs are deposited in areas where snails occur and larvae hunt actively for their prey. Snail feces and mucus were tested to determine if they had any kairomone or stimulatory effects onP. cinerella. Adult flies oviposited more frequently on substrates containing fresh snail feces than on substrates containing snail mucus or water (control). However, mucus and feces both stimulated increased search behaviour in first instar larvae. These results are discussed in relation to snail biology, and the potential for augmentation of these flies in areas affected by pest snails. PMID- 24227403 TI - Behavioral observations and measurements of aerial pheromone in a mating disruption trial against pea mothCydia nigricana F. (Lepidoptera, Tortricidae). AB - Synthetic sex pheromone of the pea mothCydia nigricana. (E,E)-8,10-dodecadien-1 yl acetate (E8,E10-12 : Ac), was applied in a 3-ha pea field at a rate of 17 g/ha, in two different dispenser formulations. Aerial concentrations within pea canopy, as determined by a field electroantennogram (EAG) apparatus, were 2 and 3 ng/m(3) in the two dispenser treatments. The validity of the EAG measurements was corroborated by sampling of field air, followed by gas chromatographic quantification ofE8,E10-12 : Ac. Males were attracted to fresh dispensers releasingE8,E10-12 : Ac plus less than 2% of the antagonisticE, Z; Z, E; andZ, Z isomers. Two days after placement, the proportion of these isomers had increased to 6%. Males were then no longer attracted to the dispensers, but were observed to fly out of the treated field. Male attraction to calling females was almost entirely suppressed, and attraction to traps baited with synthetic pheromone was significantly reduced. Larval infestation in the pheromone-treated field was 2%, compared to 36% in a control field. PMID- 24227404 TI - A method for collection, long-term storage, and bioassay of labile volatile chemosignals. AB - A procedure for headspace sampling and long-term storage of organic volatiles coupled with gas chromatographic-mass spectrometric (GC-MS) analysis was used to study the volatile chemosignals in a biological secretion prior to bioassay. The approach involved collecting the volatiles in evacuated canisters from an apparatus in which 1 ml of secretion was dispersed for headspace sampling. These canisters, stainless steel, 850 ml, and 100% internally electropolished, have been demonstrated to store volatile compounds, in chemically stable form, for several weeks. The GC-MS analyses provided the quantitation and identification of compounds from C3 through C14 at concentrations as low as 0.10 parts per billion volume. The approach was used to study chemosignals of musth temporal gland secretions (TGS) from a male Asian elephant (Elephas maximus). Fresh TGS material loses its biological activity within 1 hr. TGS material stored at -20 degrees C usually looses its activity within 30 days. The usefulness of this method for long-term storage of the volatile chemosignals was demonstrated by the retention of biologically active TGS headspace compounds, as determined through bioassays, stored in these canisters for one year. PMID- 24227405 TI - Daily rhythms of metabolic rates: Role of chemical signals in coexistence of spiny mice of the genusAcomys. AB - The common spiny mouseAcomys cahirinus and the golden spiny mouseA. russatus coexist in the extreme arid and hot parts of the Arava Rift Valley in Israel. The coexistence of these two species is through exclusion ofA. russatus from nocturnal activity byA. cahirinus, which is nocturnal. An attempt was made to study the daily activity rhythm response ofA. russatus to chemical signals released byA. cahirinus, in order to understand the mechanism of segregation. For this purpose oxygen consumption,[Formula: see text]O2, was studied in individuals ofA. russatus kept alone in a metabolic chamber in a constant ambient temperature of 32 degrees C under two photoperiod regimes: 12L:12D, and constant darkness (D:D). After three days of[Formula: see text]O2 recording under these conditions, chemical signals released fromA. cahirinus were passed through the metabolic chamber. This treatment caused a shift in the activity rhythm only ofA. russatus kept at 12:12D, while a decrease in[Formula: see text]O2 rates ofA. russatus was noted in both groups. These results suggest that chemical signals released byA. cahirinus may play a role in shiftingA. russatus toward its diurnal activity. PMID- 24227406 TI - Neutral lipids in snail-conditioned water fromBiomphalaria glabrata (Gastropoda: Planorbidae). AB - Thin-layer chromatography was used to study neutral lipids in snail-conditioned water (SCW) fromBiomphalaria glabrata snails. A major lipid fraction in SCW at 2 and 4 hr after snail incubation contained free fatty acids. Fatty acids released per snail per milliliter of water when 10 snails were incubated in 5 ml of deionized water for 4 or 2 hr was 2.4+/-0.4 ug/ml and 0.9+/-0.1 ug/ml (mean +/- SE), respectively. The amount released at 4 hr was significantly greater than at 2 hr. Snails also released free sterols, a sterol ester-hydrocarbon fraction, methyl esters, and other unidentified lipid fractions into the water. The potential of these neutral lipids to serve as chemoattractants for larval trematodes or snails remains to be determined. PMID- 24227407 TI - Analysis of characteristic human female axillary odors: Qualitative comparison to males. AB - Odors produced in the human female axillae are of both biological and commercial importance. Several studies have suggested that extracts from female underarm secretions can alter the length and timing of the female menstrual cycle. In addition, more than 1.6 billion dollars are spent annually on products to eliminate or mask the axillary odors. Our recent studies have determined that the characteristic axillary odors in males consist of C6-C11, saturated, unsaturated and branched acids, with (E)-3-methyl-2-hexenoic acid (3M2H) being the major compound in this mixture. The 3M2H appears to be carried to the skin surface bound to two proteins in the axillary secretions. Data reported here show that the same mixture of odorous compounds is found in female axillary secretions, with several minor qualitative differences. Separation of the female apocrine secretions into aqueous and organic soluble fractions demonstrated that 3M2H, and several other members of the acids in the characteristic odor, are released by hydrolysis with base. Electrophoretic separation of the proteins found in the aqueous phase of female apocrine secretions revealed a pattern identical to that seen in males. The qualitative similarity of the acidic constituents making up the characteristic axillary odors of both females and males as well as the proteins present in the aqueous phase suggest a similar origin for axillary odors in both sexes. PMID- 24227408 TI - Reproductive biology of the yellow-spotted longicorn beetle,Psacothea hilaris (pascoe) (Coleoptera: Cerambycidae). III. Identification of contact sex pheromone on female body surface. AB - A major component of female contact sex pheromone of the yellow-spotted longicorn beetle,Psacothea hilaris (Pascoe), was isolated from the elytra and identified as (Z)-21-methyl-8-pentatriacontene. The synthetic compound released the typical mating behavior including holding, mounting, and abdominal bending in males, although its activity was considerably lower than the extract of female elytra when treated on a gelatin capsule as an artificial female model. PMID- 24227409 TI - Isolation, identification, and synthesis of sex pheromone components of female tea cluster caterpillar,Andraca bipunctata walker (Lepidoptera: Bombycidae) in Taiwan. AB - Octadecanal (18:Ald), (E)-11-octadecenal (E11-18:Ald), (E)-14-octadecenal (E14 18:Ald) and (E,E)-11,14-octadecadienal (E11,E14-18:Ald) were isolated and identified as major components from the pheromone glands of the tea cluster caterpillar,Andraca bipunctata, in Taiwan by analyzing the mass spectra of gland components and their DMDS adducts. GC retention times and mass spectra of the components were in agreement with those of authentic synthetic compounds. The average amount of 18:Ald,E11-18:Ald,E14-18:Ald andE11,E14-18:Ald per female gland (1 to 3 days old) was 121+/-76, 50+/-20, 187+/-75, and 237+/-110 ng, respectively, in a ratio of 20:8:31:41. SyntheticE11,E14-18:Ald caught more males than each of the other three components or blank control in field trapping tests.E11,E14-18:Ald is reported as an insect sex pheromone for the first time. Male antenna responded toE11,E14-18:Ald strongly in an EAG analysis. Furthermore, 4 hr after the injection of PBAN (pheromone biosynthetic activating neuropeptide) into decapitated female moths (2 days old), the percentage of theE11,E14-C18 Ald in the gland extract increased from 0% to 75.5%, which was also significantly more than that of unligated and uninjected control at 55.1%. All these data indicated thatE11,E14-18:Ald is the sex pheromone of theAndraca bipunctata in Taiwan. PMID- 24227410 TI - Semiochemicals via epoxide inversion. AB - A sequence of reactions is presented for inverting the configurations of both epoxide carbons in 1,2-disubstituted epoxides. As examples, (+)-disparlure was converted to its enantiomer, (-)-disparlure, andexo-endo conversion of a cyclohexene oxide was demonstrated. PMID- 24227411 TI - Multivariate discrimination of host use by dwarf mistletoeArceuthobium vaginatum subsp.cryptopodum: Inter- and intraspecific comparisons. AB - The parasitic dwarf mistletoeArceuthobium vaginatum attacksPinus ponderosa as its primary host andP. contorta as an occasional host. Within ponderosa pine stands there is also differential parasitism among individual trees. We compared biochemical features of phloem and xylem oleoresin between infected individuals of the two pine species (N=15 for each species) and also between infected (N=30) and nearby uninfected (N=30) ponderosa pine conspecifics. There were significant differences in chemical features, both at the interspecific (P. ponderosa vs.P. contorta) and intraspecific (P. ponderosa) levels. Discriminant function analysis based on chemical features of phloem correctly classified all trees used in the analysis as eitherP. ponderosa orP. contorta, and 95% of all ponderosa pine trees as either parasitized or nonparasitized. Monoterpene composition of oleoresin was distinct between species, and differences between parasitized and nonparasitizedP. ponderosa were also significant. Many of the observed chemical differences are probably constitutive, although levels of nonstructural carbohydrates and alpha-pinene may change in response to dwarf mistletoe infection. Biochemical differences at the intraspecific level were distinct from interspecific differences. Patterns of differential attack can have genetic consequences upon both the parasite and its hosts, and, in the process, may contribute to the evolution of host races of the parasite and to the evolution of host resistance within ponderosa pine. PMID- 24227413 TI - Apple foliage enhances mating disruption of light-brown apple moth. AB - Uptake and release of pheromone and behavioral inhibitor ofEpiphyas postvittanna by apple leaves was tested using field electroantennograms (EAG), trap catches to synthetic lures and virgin females, and chemical analysis. Trap catches in single apple trees (N=3) were monitored for six cycles of six days' duration, using delta traps baited with synthetic pheromone. Polyethylene dispensers (0, 1, 10 per tree) releasing pheromone and inhibitor were present for only the first three days of each cycle. Application of 10 dispensers per tree resulted in complete disruption of trapping, which continued for one day after dispensers were removed. Over the three nights following the removal of the dispensers (days 4 6), trap catch was 0, 10, and 15% of the control catch. In contrast, the presence of only one dispenser per tree led to 0-20% of control catches, but on the three nights following dispenser removal catches were 35, 40, and 80% of the control catch. Field EAGs indicated significantly higher relative pheromone concentrations in the trees with 10 dispensers present, compared to trees with single dispensers, but removal of dispensers produced no detectable treatment effect compared to the control trees one day after dispenser removal. In a second experiment, releases of marked male moths into apple orchard plots following the removal of polyethylene dispensers (1 hr earlier that day) resulted in significantly lower catches in traps baited with virgin females in blocks that had been treated, compared to controls. Recovery of pheromone by solvent washing of leaves loaded with 50 ug of the main component of the sex pheromone (1.26 ug/cm(2)) was low (2.5%). Leaves held in a pheromone-saturated atmosphere were loaded with 0.045+/-0.007 ug pheromone/cm(2). Analysis of apple leaves taken from a pheromone-treated tree at different distances from the pheromone dispenser showed a decay of the pheromone load per square centimeter with increasing distance from the dispenser, as previously indicated by EAG. PMID- 24227412 TI - Volatile infochemicals used in host and host habitat location byCotesia flavipes Cameron andCotesia sesamiae (Cameron) (Hymenoptera: Braconidae), larval parasitoids of stemborers on graminae. AB - FemaleCotesia flavipes Cameron andCotesia sesamiae (Cameron) were attracted to odors in a Y-tube olfactometer from uninfested maize (Zea mays L.), sorghum [Sorghum bicolor (L.)], and napier grass (Pennisetum purpureum Schumach). In dual choice tests,Cotesia flavipes showed a preference for maize over sorghum, while maize and napier grass were equally attractive. In contrast,Cotesia sesamiae preferred volatiles from sorghum and napier grass over those from maize. The two parasitoids were significantly more attracted to maize infested with the stemborers,Chilo partellus (Swinhoe),Chilo orichalcociliellus Strand,Sesamia calamistis Hampson, andBusseola fusca (Fuller), than uninfested maize. In dual choice tests,Cotesia flavipes andCotesia sesamiae were unable to discriminate between odors from plants infested by the different species of stemborers. PMID- 24227414 TI - Search for tsetse attractants: A structure-activity study on 1-octen-3-ol inGlossina fuscipes fuscipes (Diptera: Glossinidae). AB - Trapping tsetse flies belonging to thepalpalis group still relies totally upon luring by visual cues even though odor-baited trapping is used effectively against themorsitans-group species. Forty-three percent of the antennal olfactory cells ofGlossina f. fuscipes, a member of thepalpalis group, respond to 1-octen-3 ol. For this species we report a structure-activity relationship between 1-octen 3-ol analogs, in which carbon chain length and the configuration of the hydroxyl and pi-bond moieties are varied, and biological activity. Although the optimum chain length for all cells sensitive to 1-octen-3-ol is eight and most cells give lower responses when the hydroxyl function is omitted, there is a clear division into two groups. One group is diverse and represents cells that appear indifferent to the presence or position of the pi bond; many will respond to such disparate structures as acetone and 3-methylphenol as well as to 1-octen-3-ol. In the other group, the structural requirements for the stimulus are more stringent; the cells appear to be specifically tuned to 1-octen-3-ol. Their thresholds are three orders of magnitude lower than those of the former group. The existence of two clusters points to a functional division in the olfactory sense. We suggest that the latter low-threshold group is involved in host detection from a distance while the former diverse group is involved in host discrimination at close range. Trap harvests with 1-octen-3-ol as a bait may have been disappointing because the appropriate mixture for generating a landing response on the traps is still lacking. PMID- 24227415 TI - Pheromone chirality of asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) (Coleoptera: Curculionidae). AB - Production of 4-methyl-5-nonanol, and 4-methyl-5-nonanone by two sympatric Asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) suggested that enantiospecificity of either compound could impart species specificity of pheromone communication. Weevil-produced, racemic 4-methyl-5-nonanol and 4-methyl 5-nonanone and their stereoselectively synthesized optical isomers were subjected to gas chromatographic-electroantennographic detection (GC-EAD) and GC-mass spectrometry (MS) on a chiral Cyclodex-B column. Only theS,S stereoisomer of 4 methyl-5-nonanol was EAD active and was produced by bothR. ferrugineus andR. vulneratus. Production and EAD activity of (S)-4-methyl-5-nonanone exceeded that of its antipode in both weevils. In field experiments in Java. (4S, 5S)-4-methyl 5-nonanol and the stereoisomeric mixture were equally attractive. The 4R,5R stereoisomer was inactive. The corresponding ketone enantiomers neither enhanced nor reduced attraction to (4S,5S)-4-methyl-5-nonanol. Lack of apparent differences betweenR. ferrugineus andR. vulneratus pheromones suggests that synonomy of both weevils should be considered unless other pre- or postzygotic reproductive isolating mechanisms are disclosed in future studies. PMID- 24227416 TI - Correlation of 1-octen-3-one with antixenotic resistance in subterranean clover cotyledons to red-legged earth mite,Halotydeus destructor (Acarina: Penthaleidae). AB - Artificially damaged cotyledons of subterranean clover (Trifolium subterraneum L.) released several volatile metabolites, including 1-octen-3-one, arising from lipid peroxidation. The amount of 1-octen-3-one produced was negatively correlated with feeding damage caused by the red-legged earth mite (Halotydeus destructor) in nine out of 10 resistant and susceptibleT. subterraneum varieties tested. The EC50 of this compound in deterring mites from feeding in a membrane bioassay was 50 ppm. Cotyledon toughness was also involved in resistance. The resistant variety, S3615D, which has the lowest toughness value among the resistant varieties, produced the highest amount of 1-octen-3-one recovered from the headspace in 1 hr. Artificially damaged cotyledons of both susceptible Dalkeith and resistant DG1007, growing in shade, showed lower toughness, but had enhanced production of C8 volatile compounds and were avoided by mites during a 3 hr feeding test. When both 1-octen-3-one content and cotyledon toughness value were taken as cofactors in resistance, the resultant multiplication value yielded a more significantly negative correlation with mite feeding damage scores within the 10 varieties than either factor alone. We conclude that 1-octen-3-one has a role in resistance of subclover cotyledon to the mite. PMID- 24227417 TI - Anal gland secretion of European mole: Volatile constituents and significance in territorial maintenance. AB - The chemical composition of the volatile components of the anal gland secretion of mature and immature moles of both sexes was examined by gas chromatography and mass spectrometry. The compounds in the secretion of adult males appear to vary little throughout the year and are similar to those from the adult female outside the breeding season. The secretions are dominated by C5-C10 carboxylic acids. Female glands regress as they enter proestrus, accompanied by profound changes in the chemical composition of the secretion with early disappearance of the carboxylic acids. In juvenile moles, the composition of the secretion changes as the animal matures, with carboxylic acids becoming dominant only as the animal reaches maturity. Anal gland secretion probably plays an important role in territorial maintenance. PMID- 24227418 TI - Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty. AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. Insulin resistance has a key role in metabolic changes in these children. Insulin levels elevate as puberty commences in every individual. WHAT THIS STUDY ADDS: Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes. BACKGROUND: Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears. OBJECTIVES: Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. METHODS: Three hundred thirty-four obese children (5-19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). RESULTS: Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 +/- 1.03 vs. 8.00 +/- 0.69; P < 0.01), but no difference was discovered during and after puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 +/- 1.26 vs. 2.54 +/- 0.23; P < 0.01). CMR children have dyslipidaemia before the onset of puberty. CONCLUSIONS: CMR is associated with increased postprandial IR in pre-pubertal and increased fasting IR in post-pubertal obese children. Dyslipidaemia appeared already in pre-puberty in CMR children. PMID- 24227419 TI - Interaction ofBdellovibrio with Its prey in mixed microbial populations. AB - The interaction ofBdellovibrio with its prey can be affected by the presence of other microorganisms regardless of whether they serve as a prey for the bdellovibrios. This was shown in a system in which the fate of one prey could be followed in mixed bacterial populations thanks to a specific trait, bioluminescence. The attacking bdellovibrio causes decay of bioluminescence, and the rate of light decay of the population indicates the rate at which the luminous bacteria are attacked. Using this system it was found that different bacteria affected the predatorprey interaction in different ways: some "competed" with the original prey for the predator; others enhanced the activity of the predator toward the original prey, and others inhibited it. The significance of these findings in relation to the distribution and activity ofBdellovibrio in the natural ecosystem is discussed. PMID- 24227420 TI - Inhibition of the predatory activity ofBdellovibrio by various environmental pollutants. AB - The predatory activity of bdellovibrios is affected by various environmental pollutants such as detergents, heavy metals, and pesticides. This was shown in a two-membered system ofBdellovibrio andPhotobacterium, in which the effect of the predator on the bioluminescence of the prey indicated the activity of the former. The high sensitivity of the bdellovibrios toward certain chemicals (e.g., CdCl2) indicates the possibility of using the system for biological monitoring of those chemicals. PMID- 24227421 TI - Problems in estimating growth rates of marine phytoplankton from short-term(14)C assays. AB - Growth rate estimates (MU') of phytoplankton populations that were sampled from nitrogen-limited continuous cultures and then incubated for short durations in batch culture with added(14)C-HCO3 (-) were significantly different than steady state growth rates (MU) for 3 of 5 marine phytoplankton species. Two diatoms,Thalassiosira weissflogii andChaetoceros simplex, displayed virtually identical growth rates (MU=MU') over a wide range ofMU, whereasMU' for a third diatom,Phaeodactylum tricornutum, was overestimated by an average of 40% compared toMU. In contrast,MU' was underestimated by the(14)C technique for the two remaining species: up to 40% at a steady-stateMU of 1.0 day(-1) for the chlorophyteDunaliella tertiolecta and up to 100% atMU of 1.4 day(-1) for the haptophytePavlova lutheri. For the latter two species the divergence betweenMU andMU' appeared to increase with increasing steady-stateMU. A simple model of labeled and total carbon flow between the aqueous phase and cellular biomass was constructed to demonstrate that respiration was negligible whenMU=MU', but was significant whenMU'>MU. In the cases in whichMU'141.0 and 276.2->191.1 were used to quantify meropenem and rolipram, respectively. A fast and simple solid phase extraction method was optimized for extraction of meropenem from rat plasma. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability, matrix effect, dilution integrity as per regulatory guidelines. The developed method was selective with no interfering components at the retention time of meropenem and rolipram. The assay demonstrated acceptable linearity (R(2)>0.99) over a dynamic range of 0.19-201.40 ug/mL. The method exhibited excellent and acceptable precision and accuracy, and produced consistent recoveries. The method demonstrated excellent stability of meropenem in rat plasma under studied conditions investigated. Finally, the validated method was successfully applied to quantify meropenem levels in rat plasma of a dose escalation study. PMID- 24227473 TI - Antiproliferative activity of novel thiophene and thienopyrimidine derivatives. AB - A novel series of newly synthesized thiophene derivatives, ethyl-4,5-dimethyl-2 (3-(3,4,5-trimethoxyphenyl)thioureido)thiophene-3-carboxylate 3, ethyl-2-[(2 (dimethylamino)ethoxy)mercapto)methyleneamino)]-4,5-dimethyl-thiophene-3 carboxylate 9, thienopyrimidines 4, 7, 10-20, triazolothienopyrimidines 5, 6 were prepared and tested for their antiproliferative activity. The structures of the synthesized compounds were confirmed on the basis of elemental analysis, IR, (1)H NMR, (13)C-NMR and mass spectral data. The results showed that the synthesized compounds were more active on breast cancer than on colon cancer cell lines and the most potent compounds in this study are compounds 3 and 13 which exerted remarkable activity against MDA-MB-231 (breast cancer) and HT-29 (colon cancer) cell lines with IC50 values (40.68, 49.22 MUM) for compound 3 and (34.04, 45.62 MUM) for compound 13. Also, compounds 4-6, 9 showed a moderate activity against breast cancer cell line, while compounds 15, 19 and 20 showed no activity. PMID- 24227474 TI - Antidepressant and anxiolytic properties of the methanolic extract of Momordica charantia Linn (Cucurbitaceae) and its mechanism of action. AB - BACKGROUND: The whole plant of Momordica charantia Linn (Cucurbitaceae) is used in traditional African medicine in the management of depressive illness. METHODS: Momordica charantia (MC) (50-400 mg/kg, p.o.) was administered 1 h before behavioural studies using the forced swimming test (FST) and tail suspension test (TST) to investigate antidepressant-like effect while the anxiolytic-like effect was evaluated with elevated plus maze test (EPM), hole-board test (HBT), and light-dark test (LDT). RESULTS: Acute treatment with MC (50-400 mg/kg) significantly increased swimming time (86.51%) and reduced the duration of immobility (52.35%) in FST and TST with peak effects observed at 200 mg/kg, respectively, in comparison to control. The pretreatment of mice with either sulpiride (dopamine D2 receptor antagonist), or metergoline (5-HT2 receptor antagonist), or cyproheptadine (5-HT2 receptor antagonist), or prazosin (alpha1 adrenoceptor antagonist), or yohimbine (alpha2-adrenoceptor antagonist), and atropine (muscarinic cholinergic receptor antagonist) 15 min before oral administration of MC (200 mg/kg) significantly blocked its anti-immobility effect. Similarly, MC (200 mg/kg) significantly reduced anxiety by increasing the open arm exploration (64.27%) in EPM, number of head-dips in HBT (34.38%), and time spent in light compartment (29.38%) in the LDT. However, pretreatment with flumazenil (GABAA receptor antagonist) 15 min before MC (200 mg/kg) significantly blocked (54.76%) its anxiolytic effect. CONCLUSION: The findings in this study showed that MC possesses antidepressant-like effect that is dependent on the serotonergic (5-HT2 receptor), noradrenergic (alpha1- and alpha2-adrenoceptors), dopaminergic (D2 receptor), and muscarinic cholinergic systems and an anxiolytic like effect that might involve an action on benzodiazepine-type receptor. PMID- 24227475 TI - Evaluation of serum lipid profile in patients with hypertension living in a coastal region of Bangladesh. AB - Serum lipid levels are greatly controlled by genetic and environmental factors. When investigating the relationship between lipid disturbances and hypertension it is necessary to use local data on blood lipid profile in each region. Unfortunately, there is no literature reporting the lipid profile in hypertensive patients in coastal region of Bangladesh. The present study was conducted as a case-control study with 100 hypertensive patients as cases and equal number of normotensive individuals as controls. Socio-demographic, anthropometric and clinical data of both patients and controls were collected. Serum lipid parameters were analyzed biochemically. Independent sample t-test, Chi-Square test and Pearson's correlation test were done for the statistical analysis using the statistical software package SPSS. Our study found that serum total cholesterol (TC), triglyceride (TG), LDL, VLDL, TC/HDL, LDL/HDL were significantly higher (p<0.05) whereas the level of HDL cholesterol was significantly lower in hypertensive patients as compared to control subjects (p<0.05). Pearson's correlation analysis reveals that HDL cholesterol was inversely correlated with systolic and diastolic blood pressure in both patient and control groups. But serum TC, TG, LDL and HDL cholesterol were directly correlated with systolic and diastolic blood pressure in both groups. This study explored that hypertensive patients have higher level of TC, TG, LDL and VLDL cholesterol but lower level of HDL cholesterol than the normotensive subjects. Routine investigation of lipid profile in hypertensive patients may help to prevent further aggravation and risks of coronary artery diseases. PMID- 24227476 TI - Increased gene expression of glucose transporters in the mouse brain after treatment with fluoxetine and pergolide. AB - Glucose transporters play key roles in the homeostatic control of brain functions. In the present study, we examined the effect of fluoxetine, a selective serotonin reuptake inhibitor, and pergolide, a dopamine D receptor agonist, on the gene expression levels of glucose transporters in the mouse brain. mRNAs for 8 sodium-independent glucose transporters (GLUTs), other than GLUT4 and GLUT9, and sodium-dependent glucose transporter 1 (SGLT1) were confirmed to be expressed in brain tissue. Fluoxetine and pergolide significantly increased the expression levels of mRNAs for GLUT1 and GLUT10 in the brain. Furthermore, the expression of GLUT6 in tissue was increased by administering pergolide to mice. On the other hand, fluoxetine and pergolide had no effect on the expression levels of mRNAs for the other GLUTs and SGLT1. Therefore, we concluded that the gene expression of several GLUT isoforms in the mouse brain was affected by the treatment with fluoxetine and pergolide. PMID- 24227477 TI - In vivo evaluation of axial integrity of coronary stents using intravascular ultrasound: Insights on longitudinal stent deformation. AB - OBJECTIVE: To evaluate the axial integrity of different coronary stents using intravascular ultrasound (IVUS). BACKGROUND: Longitudinal stent deformation was recently reported. METHODS: Consecutive patients who underwent IVUS analysis after drug-eluting stent (DES) implantation for de novo coronary lesions were evaluated. Stent length was compared with label length for calculation of absolute change and relative difference (absolute change divided by label length). RESULTS: A total of 233 DES utilizing five different platforms were included. The median absolute change in stent length was 0.90 mm (interquartile range [IQR] 0.48-1.39) and the relative difference was 5.24% (IQR 2.55-8.29). There was no significant difference among the groups in median absolute or relative change: Cypher 0.89 mm/3.89%, Taxus 0.88 mm/5.39%, Endeavor 1.16 mm/6.77%, Xience V 0.86 mm/5.80%, and PROMUS Element 0.79 mm/5.34% (P = 0.085, P = 0.072, respectively). Multivariate logistic regression revealed that the Cypher stent was independently correlated with a lower change in length, whereas stent label length and deployment pressure were correlated with higher absolute change. CONCLUSION: The axial integrity of DES platforms examined in vivo was high, with only mild changes in stent length after implantation. While there are differences between first- and second-generation DES, axial integrity among second-generation DES was similar. PMID- 24227478 TI - Sequence-derived structural features driving proteolytic processing. AB - Proteolytic signaling, or regulated proteolysis, is an essential part of many important pathways such as Notch, Wnt, and Hedgehog. How the structure of the cleaved substrate regions influences the efficacy of proteolytic processing remains underexplored. Here, we analyzed the relative importance in proteolysis of various structural features derived from substrate sequences using a dataset of more than 5000 experimentally verified proteolytic events captured in CutDB. Accessibility to the solvent was recognized as an essential property of a proteolytically processed polypeptide chain. Proteolytic events were found nearly uniformly distributed among three types of secondary structure, although with some enrichment in loops. Cleavages in alpha-helices were found to be relatively abundant in regions apparently prone to unfolding, while cleavages in beta structures tended to be located at the periphery of beta-sheets. Application of the same statistical procedures to proteolytic events divided into separate sets according to the catalytic classes of proteases proved consistency of the results and confirmed that the structural mechanisms of proteolysis are universal. The estimated prediction power of sequence-derived structural features, which turned out to be sufficiently high, presents a rationale for their use in bioinformatic prediction of proteolytic events. PMID- 24227480 TI - Phytotoxicity of cacalol and some derivatives obtained from the roots ofPsacalium decompositum (A. Gray) H. Rob. & Brettell (Asteraceae), matarique or maturin. AB - The effect of cacalol and extracts (water and petroleum ether) derived from the roots ofPsacalium decompositum (Asteraceae) on the germination and radicle growth of two plants.Amaranthus hypochondriacus (Amaranthaceae) andEchinochloa crusgalli (Poaceae), and on the radial growth of four phytopathogenic fungi is described. The activity of two cacalol derivatives (methyl cacalol and cacalol acetate) was also investigated. Germination ofA. hypochondriacus was inhibited by almost all the treatments. The extracts and cacalol produced a significant inhibition of radicle growth ofA. hypochondriacus andE. crusgalli. Cacalol acetate showed a specific inhibition onE. crusgalli, and methyl cacalol significantly inhibited the growth ofA. hypochondriacus. In general, antifungal activity depended upon the target fungi and the concentration of each treatment. Cacalol had also effects on the morphology and coloration of the fungal mycelium. The bioactivity shown by the extracts ofPsacalium decompositum on the tested seeds and fungi is mainly due to their content in cacalol. PMID- 24227479 TI - Genomewide association study in cervical dystonia demonstrates possible association with sodium leak channel. AB - Dystonia is a common movement disorder. A number of monogenic causes have been identified. However, the majority of dystonia cases are not explained by single gene defects. Cervical dystonia is one of the commonest forms without genetic causes identified. This pilot study aimed to identify large effect-size risk loci in cervical dystonia. A genomewide association study (GWAS) was performed. British resident cervical dystonia patients of European descent were genotyped using the Illumina-610-Quad. Comparison was made with controls of European descent from the Wellcome Trust Case Control Consortium using logistic regression algorithm from PLINK. SNPs not genotyped by the array were imputed with 1000 Genomes Project data using the MaCH algorithm and minimac. Postimputation analysis was done with the mach2dat algorithm using a logistic regression model. After quality control measures, 212 cases were compared with 5173 controls. No single SNP passed the genomewide significant level of 5 * 10(-8) in the analysis of genotyped SNP in PLINK. Postimputation, there were 5 clusters of SNPs that had P value <5 * 10(-6) , and the best cluster of SNPs was found near exon 1 of NALCN, (sodium leak channel) with P = 9.76 * 10(-7) . Several potential regions were found in the GWAS and imputation analysis. The lowest P value was found in NALCN. Dysfunction of this ion channel is a plausible cause for dystonia. Further replication in another cohort is needed to confirm this finding. We make this data publicly available to encourage further analyses of this disorder. PMID- 24227481 TI - Purification and characterization of new fatty acids with antibiotic activity produced bySporothrix flocculosa. AB - Chloroform extracts from a culture broth of the biocontrol fungusSporothrix flocculosa were separated by thin-layer chromatography (TLC). Compounds with antifungal activity were revealed with theCladosporium cucumerinum bioassay on TLC plates and were isolated by using silica gel column, preparative TLC, and reverse-phase high-performance liquid chromatography (RP-HPLC). They were identified by standard methods of nuclear magnetic resonance (NMR), gas chromatography (GC), mass spectrometry (MS), and infrared spectrum (IR). In addition to an active molecule previously described, two new fatty acids with antibiotic activity were characterized, 9-heptadecenoic acid and 6-methyl-9 heptadecenoic acid, the latter displaying the strongest activity among all three active molecules. This high number of active metabolites produced byS. flocculosa would explain its rapid and strong activity as a biocontrol agent of powdery mildews. In this context, screening ofS. flocculosa isolates for increased production of these molecules should help in selection of candidates with superior biocontrol properties. PMID- 24227482 TI - Efficacy of nonpheromone communication disruptants of codling moth (Cydia pomonella): Effect of pheromone isomers and of distance between calling females and dispensers. AB - Field tests comparing the ability of codlemone, (E,E)-8,10-dodecadien-1-ol, and isomers of codlemone to disrupt pheromonal communication of codling moth were carried out. In a pear orchard, four nonisomerizing, gray septa dispensers were placed in the upper canopy of each tree containing a trap baited with 10 virgin female codling moths. The dispensers were at trap height and 70 cm from the edge of each trap. Trap catches of released male codling moths in three test areas were compared simultaneously when trees in each of the test areas contained unbaited dispensers, dispensers with 1 mg of codlemone containing 1% isomers, and dispensers with 1 mg of a test communication disruptant. When the test disruptant was an equilibrium mixture of codlemone and its isomers (61% codlemone, 39% isomers), the percent communication disruption was 86.8% compared to 68.7% for codlemone (P < 0.001). When the disruptant was (E,Z)-8,10-dodecadien-1-ol (94%EZ, 3%EE), the percentage disruption was 86.4% compared to 62.7% for codlemone (P < 0.002). These results show that the previously reported superior disruptant potency (relative to codlemone) of compositions containing codlemone with a high percentage of isomers was not a result of the proximity of the dispensers to the traps. The percent disruption of compositions of codlemone with 10 and 20% isomers was also determined. A plot of percentage disruption versus logarithm of percentage of nonpheromone isomers in the mixture from 1% to 97% gave a straight line withR (2)=0.93. PMID- 24227483 TI - Effects of organic solvent extracts from herbage on feeding behavior in goats. AB - The effects of organic solvent extracts from perennial ryegrass (Lolium perenne L. cv. Friend), orchardgrass (Dactylis glomerata L. cv. Akimidori) andLolium *Festuca hybrid on the hay consumption of goats were measured by simple two choice feeding assays. Orchardgrass hay treated with methanol extracts (resuspended in water) of perennial ryegrass showed an increased intake by goats compared to untreated hay (P < 0.01). The palatability of hay tended to be slightly decreased by spraying it with pentane extract of perennial ryegrass and orchardgrass. Furthermore, extracts of hybrid with pentane inhibited goats from feeding (P < 0.05). Methanol extract stimulated hay consumption whereas the pentane extracts did not change or reduce intake. PMID- 24227484 TI - Pheromone specificity inEriocrania semipurpurella (Stephens) andE. sangii (Wood) (Lepidoptera: Eriocraniidae) based on chirality of semiochemicals. AB - The fifth abdominal segment of femaleEriocrania semipurpurella (Stephens) andE. sangii (Wood) contains a pair of exocrine glands. Hexane extracts of this segment were prepared from both species and analyzed by gas chromatography with simultaneous flame ionization and electroantennographic detection (EAD). For both species, the EAD active peaks were identified as nonan-2-one, (Z)-6-nonen-2-one, and (Z)-6-nonen-2-ol by means of mass spectrometry and comparison of retention indices with those of synthetic standards. Enantiomeric separation of chiral alcohols from the female extracts was achieved by gas chromatographic analysis on a cyclodextrin column. InE. semipurpurella, a mixture of (2S,6Z)-nonen-2-ol and (2R,6Z)-nonen-2-ol (2: I) was found, whereas inE. sangii (2S,6Z)-nonen-2-ol was the predominant enantiomer and only traces of theR enantiomer were indicated by the antennal response. In field tests, a blend of the three compounds was not attractive to conspecific males. A subtractive assay showed that the alcohol in various enantiomeric mixtures was the only attractive compound, whereas addition of (Z)-6-nonen-2-one to the alcohol completely inhibited the attraction of both species. A trapping experiment including a wide range of ratios between theR andS enantiomers showed that baits containing 95-100% of theS enantiomer were attractive to maleE. sangii, whereas males ofE. semipurpurella were attracted to all tested ratios of the enantiomers. However, the response profiles of maleE. semipurpurella differed between populations from southern Sweden, south Finland, and the Kola Peninsula in Russia. In south Sweden males were maximally attracted to a racemic mixture of the alcohols. At the Kola PeninsulaE. semipurpurella was attracted to baits containing 95-100% of theR enantiomer. In south Finland all tested ratios between 0 and 100%R enantiomer trappedE. semipurpurella, but the trap catches appeared to be bimodally distributed with peaks around 15 and 70%R enantiomer. The trapping results suggest the existence of pheromone races or sibling species among the specimens identified asE. semipurpurella. PMID- 24227485 TI - Location and behavioral effects of lectin binding on entomopathogenic nematodes with different foraging strategies. AB - Lectins have been used to locate and ascribe a function to sensory organs of nematodes. We had two objectives: (1) to determine the location of carbohydrate exudates on the surface of three species of entomopathogenic nematodes with different foraging strategies and (2) to evaluate the importance of carbohydrates in host finding and recognition.Steinernema carpocapsae finds hosts by ambushing, and most individuals respond poorly to host cues. No specific areas of lectin binding were recorded for this species. Wheat germ agglutinin bound specifically to the anterior region ofHeterorhabditis bacteriophora and to the anterior and posterior ofS. glaseri. These two nematode species are cruise foragers and are highly responsive to host cues. The behavioral effects of lectins varied. None of the species' responses to volatile host cues was affected.S. carpocapsae's rate of attachment during ambushing was increased by treatment with WGA, and this effect was negated by treatment with a competing sugar (N-acetylglucosamine). The infectivity ofS. glaseri in an assay that required movement through 5 cm of sand to find the host was significantly decreased by treatment with WGA. PMID- 24227487 TI - Seasonal change in nagilactone contents in leaves inPodocarpus nagi forest. AB - Nagilactones isolated fromPodocarpus nagi (Thunb.) Zoll. et Moritz. are known by their physiological activities as a plant growth inhibitor or antiherbivory substance. As the first step in clarifying the nagilactone dynamics in a forest canopy, the seasonal variations in nagilactone contents in leaves and mass of nagilactones accumulated in the canopy were examined at Mt. Mikasa, Nara City, central Japan. Nagilactone content in mature leaves dropped sharply in May, when new leaves flushed. The nagilactone content of new leaves was far greater than that of mature leaves, implying a translocation of nagilactones from old leaves to new leaves. The total mass of nagilactones in the canopy was 3.9 kg/ha. PMID- 24227486 TI - Effects of diet on localized defecation by Northern Pike,Esox lucius. AB - Fathead minnows (Pimephales promelas) are able to detect conspecific alarm pheromone in the feces of northern pike (Esox lucius) and have been shown to avoid areas labeled with the feces of pike that were fed minnows. The minnows did not avoid areas labeled with the feces of pike that were fed swordtails (Xiphophorous helleri), which lack ostariophysan alarm pheromone. In laboratory experiments, pike fed a diet of minnows localized their defecation away from their foraging area. It has been suggested that in doing so, pike may remove chemical cues that label their foraging area as dangerous to prey species. As yet there has been no conclusive evidence to support this hypothesis. In this experiment, we test the effects of different predator diets on localized defecation by pike. Pike were fed minnows, swordtails, or mice (Mus musculus). Swordtails and mice lack ostariophysan alarm pheromones. Area use and location of feces were recorded. Pike fed minnows spent significantly more time in the home area (i.e., area of the test tank where they were fed) and defecated significantly more often in the opposite end of the tank. Pike fed swordtails also exhibited a significant preference for the home area in area use, while those fed mice showed no such preference. When fed either swordtails or mice, there was no significant difference between the proportion of time spent and proportion of feces in each area of the test tank. These data suggest that pike localize their defecation only when consuming prey items containing alarm pheromone. The current findings support the hypothesis that pike localize their defecation to remove chemical cues from the foraging area of the home range in order to avoid chemically labeling their foraging area as dangerous to prey. PMID- 24227488 TI - Fate of the chromene encecalin in the interaction ofEncelia farinosa and its specialized herbivoreTrirhabda geminata. AB - Leaf beetles of the speciesTrirhabda geminata are specialized herbivores that are able to feed on the chemically well-protected foliage of the desert sunflowerEncelia farinosa, which contains the insecticidal chromene derivative encecalin. Chemical analysis of the beetles and their fecal excretions indicated that encecalin is present only in the alimentary canal and is not absorbed across the gut membrane, as previously shown for other herbivorous insects (e.g., the Egyptian armyworm,Spodoptera littoralis) that are susceptible to this chromene derivative. Further differences betweenT. geminata and nonadapted insects were observed with regard to the metabolism of encecalin. Whereas the encecalin resistent leaf beetles metabolize encecalin mainly to encecalol by reduction of the acetyl group, susceptible insects, such as larvae ofS. littoralis, metabolize encecalin mainly by exoxidation of the 3,4 double bond, which creates a powerful alkylating agent and is responsible for the toxicity of encecalin. Reductive rather than oxidative metabolism of encecalin therefore seems important for the resistance ofT. geminata against the chemical defense of their host plantE. farinosa. PMID- 24227489 TI - Attractiveness to mexican fruit flies of combinations of acetic acid with ammonium/amino attractants with emphasis on effects of hunger. AB - Ammonium acetate was more attractive than other ammonium salts to Mexican fruit flies (Anastrepha ludens) in an orchard test. We hypothesized that acetic acid enhanced the attractiveness of ammonia in the orchard test and that acetic acid may similarly enhance attractiveness of AMPu, an attractant consisting of a mixture of ammonium bicarbonate or ammonium carbonate, methylamine HCl, and putrescine. In laboratory experiments, acetic acid was attractive to flies deprived of either yeast hydrolysate or both sugar and yeast hydrolysate but not to flies fed both sugar and yeast hydrolysate. AMPu/acetic acid combinations were more attractive than AMPu alone to flies deprived of both sugar and yeast hydrolysate but not to flies fed sugar, regardless of yeast hydrolysate deprivation status. Acetic acid is the first attractant found that has become more attractive with both sugar and protein deprivation in studies withA. ludens. It is also the first that has enhanced the attractiveness of another attractant type. In orchard tests, yellow sticky panels baited with either AMPu or 17 mg of acetic acid were at least six times more attractive than unbaited panels. However, panels baited with both acetic acid (17-68 mg) and AMPu were less attractive than AMPu alone. These results differed from the laboratory data in which combinations were never less attractive than AMPu alone. PMID- 24227490 TI - Identification and bioassay of kairomones forHelicoverpa zea. AB - Hexane extracts of leaves of 307 accessions from 73 host plant species ofHelicoverpa zea were analyzed by gas chromatography (GC) and used forH. zea oviposition and neonate larvae orientation bioassays. The gas chromatographic (GC) retention times of compounds statistically associated with behavioral activity were identified by correlation of GC peak area with oviposition and larval orientation preferences. Although taxonomically diverse in their origin, compounds for study were purified from extracts of species of the genusLycopersicon, due to their relative abundance. The structures of eight long chain alkanes associated with oviposition preference were assigned by mass spectrometry, and the structures of five similarly associated organic acids and a terpenoid alkene were identified by(1)H and(13)C nuclear magnetic resonance spectroscopy. The structures of a number of other phytochemicals from the plant leaves were identified for comparative purposes, including a previously unknown terpene, 7-epizingiberene. Bioassays were performed on the isolated acids and on the alkane wax fractions of severalLycopersicon species, and significant differences were found in oviposition stimulation for both classes of compounds. Of the hundreds of compounds found in the extracts, none were observed to act as oviposition deterrents. The results of these bioassays may be useful in explaining the broad host range ofH. zea, as well as the process and evolution of host plant selection for oviposition. PMID- 24227491 TI - Role of plant volatiles in the search for a host by parasitoidDiglyphus isaea (Hymenoptera: Eulophidae). AB - Diglyphus isaea Walker is a larval ectoparasitoid used in biological pest control against the American serpentine leaf minerLiriomyza trifolii Burgess. We studied the parasitoid's host searching behavior, using olfactometric methods. Our data show that the parasitoids locate host larvae (a leafmining dipteran) on the basis of volatile signals released by the plant-host complex. FemaleD. isaea are strongly attracted to the odors arising from damaged bean plants, whereas they show practically no response to intact plants. The results of our chemical analyses showed that about 15 components were present, two of which,cis-3-hexen-1 ol and 4-hydroxy-4-methyl-2-pentanone, were present in significantly larger quantities in the leaf extracts from mined or damaged bean plants than in those from healthy plants. The damage inflicted by the host larvae on these plants triggers the release of larger amounts of these substances, which probably lead the parasites to their hosts. The compounds thus act as synomones. PMID- 24227492 TI - Relationships betweenDendroctonus micans Kug. (Coleoptera: Scolytidae) survival and development and biochemical changes in Norway Spruce,Picea abies (L.) Karst., phloem caused by mechanical wounding. AB - The bark of Norway spruce trees,Picea abies (L.) Karst., was wounded to produce areas of bark with differing biochemical characteristics. Adults and larvae ofDendroctonus micans Kug. were inserted into these trees at points around the wounds. Larval survival was higher, larval dry weights were higher, and adults were more likely to oviposit at sites around the wound that had higher phloem moisture contents. Larvae showed higher survival and dry weights in phloem with low terpene contents. Adults oviposited in phloem with lower stilbene glucoside contents. Phloem moisture differed at sites around the wound compared with that at a control site away from the wound, and the nitrogen content of entire bark cores was higher above wounds than at control sites away from the wounds. Phloem moisture correlated with the nitrogen content of entire bark. Phloem terpene contents correlated with each other, as did the stilbene contents. Associations between the host exploitation pattern ofD. micans and the biochemistry of the host phloem are discussed in relation to preselection by adults of sites suitable for larval development. PMID- 24227493 TI - Growth and physiological responses of Black Spruce (Picea mariana) to sites dominated byLedum groenlandicum. AB - Growth and physiological parameters of black spruce planted eight years previously were compared at sites with and withoutLedum groenlandicum to quantify the adverse effects on black spruce inLedum sites. Tree height, crown diameter, and dry weights of stems, branches, and needles of black spruce were significantly less at theLedum-dominated sites. Annual stem height, basal diameter, growth ring width, and cumulative wood volume of black spruce were significantly reduced in theLedum sites compared to those of the non-Ledum sites. Yearly growth of black spruce in the first seven years after planting was more affected in theLedum site than the eighth year's growth. Foliar nutrient analysis of black spruce in theLedum site showed an overall imbalance in nutrient accumulation. Black spruce growing in theLedum site had higher foliar concentrations of Al, Ca, Fe, Ni, and S and lower concentrations of N and Si than those growing in the non-Ledum site. Black spruce growing in theLedum site also had a higher foliar phenolic content. Preliminary experiments suggest thatLedum has the potential to leach water-soluble phenolics to its immediate organic soil. PMID- 24227494 TI - Action of antialgal compounds fromJuncus effusus L. onSelenastrum capricornutum. AB - Twenty-nine free and glucosylated dihydrophenanthrenes and tetrahydropyrenes isolated fromJuncus effusus have been tested against the unicellular green algaSelenastrum capricornutum. The free compounds showed a strong inhibitory activity, while the glucosides were inactive or had a slight stimulating effect on growth. Tetrahydropyrene33, obtained by hydrolysis of the naturalbeta glucosides29 and30 or by hemisynthesis from1, is the most active compound, causing 90% inhibition of the growth at 2.5 * 10(-5) M concentration. Synthetic alpha-glucosides28, 31, and32 showed comparable activity to those of29 and30. PMID- 24227495 TI - Competition between heterotrophic and autotrophic microplankton for dissolved nutrients. AB - When a heterotrophic (Rhodotorula rubra) and a phototrophic (Selenastrum capricornutum) plankton were grown together in dilute phosphate (Pi) continuous cultures, coexistence occurred only when the heterotroph was growthrate limited by organic carbon (C). Because of its higher affinity for Pi, and because C starvation does not affect the heterotrophic yeast's ability to transport Pi, the concentration of organic carbon indirectly controlled the biomass of the phototroph. The results support a threshold model of microbial growth. PMID- 24227496 TI - Effects of random motility on growth of bacterial populations. AB - A spatially distributed mathematical model is developed to elucidate the effects of chemical diffusion and cell motility as well as cell growth, death, and substrate uptake on steady-state bacterial population growth in a finite, one dimensional, nonmixed region. The situation considered is growth limited by a diffusing substrate from an adjacent phase not accessible to the bacteria. Chemotactic movement is not considered in this paper; we consider only "randomwalk"-type random motility behavior here. The following important general concepts are suggested by the results of our theoretical analysis: (a) The significance of random motility effects depends on the magnitude of the ratioMU/kL (2), whereMU is the bacterial random motility coefficient,k is the growth rate constant, andL is the linear dimension of the confined growth region. (b) In steady-state growth in a confined region, the bacterial population size decreases asMU increases. (c) The effect ofMU on population size can be great; in fact, sometimes relative population sizes of two species can be governed primarily by the relative values ofMU rather than by the relative values ofk. PMID- 24227497 TI - Measurement of the microbial biomass in intact cores of soil. AB - The fumigation/respiration technique was used to estimate the size of the soil microbial biomass. Sieving decreased the biomass in winter but increased it in summer; we suggest that this was a consequence of the different substrates available and the different microbial populations during the year. The flush in respiration following fumigation correlated significantly with the CO2-C produced 10 days after fumigation (X), so that in the soils studied by us the biomass (B) can be calculated from Bk=0.673X-3.53, wherek is the fraction of fumigated organisms mineralized to CO2, thus avoiding the need to measure CO2 production from unfumigated cores. PMID- 24227498 TI - Characteristics of the heterotrophic bacterial populations in hypersaline environments of different salt concentrations. AB - Solar salterns, based on a multi-pond system, give a discontinuous gradient of salt concentrations. The heterotrophic bacterial populations of ponds containing from 10% salt to saturation have been studied. Saltern samples were spread on agar plates containing different media for halophilic bacteria and one medium made with water of the pond plus nutrients. Replica plating was done to determine the salt range for growth of the colonies. We studied 150 strains to determine the salt spectra of growth, the morphology, and nutrient requirements. The following conclusions were reached: (a) In salt concentrations above 10% (total salts), most bacteria are halophilic and few are halotolerant; (b) the two types of halophilic bacteria, moderate and extreme, show different distributions; in these ponds a narrow overlap exists between 25% and 32% salts with moderate halophiles predominating below this interval and extreme halophiles above it; (c) the populations of moderate halophiles are highly heterogeneous, and the salt concentration of their habitat affects their taxonomic composition, salt range for growth, and nutrient requirements. The population composition of extreme halophiles is less affected by the salt concentrations at which these bacteria are found. PMID- 24227499 TI - Contribution of periphytic bacteria to the concentration of chromium in the crabHelice crassa. AB - Periphytic bacteria found on the carapace and gills of crabs collected from near a tannery effluent outlet were shown to be able to concentrate chromium. By concentrating Cr, the bacteria contributed to the total Cr concentration of the crabs. Since crabs and other crustaceans are eaten by bottom feeding fish, bacteria may be contributing to the passage of Cr up the food chain. PMID- 24227500 TI - Ecology of bacterial communities in the schistosomiasis vector snailBiomphalaria glabrata. AB - The internal colony-forming bacterial flora of the schistosome intermediate host snailBiomphalaria glabrata (Say) has been characterized in ca. 500 individual snails from Puerto Rico, Guadeloupe, and St. Lucia, and from laboratory aquaria. Freshly captured wild snails harbor 2-40*10(6) CFU.g(-1), and healthy aquarium snails harbor 4-16*10(7) CFU.g(-1), whereas moribund individuals have 4-10 times as many bacteria as healthy individuals from the same habitats.Pseudomonas spp. are the most common predominant bacteria in normal snails, whereasAcinetobacter, Aeromonas, andMoraxella spp. predominate in moribund snails. External bacterial populations in water appear to have little effect on the composition and size of the flora in any snail. In addition to normal (healthy) and moribund snails, a third group of snails has been distinguished on the basis of internal bacterial density and predominating genera. These "high-density" snails may have undergone stresses and may harbor opportunistic pathogens. The microfloras of wild and laboratory-reared snails can be altered and stimulated to increase in density by crowding the snails or treating them with antibiotics. PMID- 24227501 TI - Ecological study of twoNitrobacter serotypes coexisting in the same soil. AB - The problem of competition betweenNitrobacter strains was posed by the fact that two serotypes (N.w and L) coexisted in a soil, as shown by immunofluorescence. The L serotype had a lower growth rate in pure culture than serotype N.w, as well as a slower nitrifying activity when inoculated to a sterilized soil percolated with NO2 (-) solution. When both serotypes were inoculated together, only N.w was observed by immunofluorescence at the end of the percolation; when in the control soil the two serotypes were identified, strain L always adhered to particles. Maintenance of the two serotypes in the soil could be explained as their exploitation of distinct ecological niches. Thus the relative in situ importance of the two strains is governed by environmental conditions. PMID- 24227502 TI - A mesoporous carbon-supported Pt nanocatalyst for the conversion of lignocellulose to sugar alcohols. AB - The conversion of lignocellulose is a crucial topic in the renewable and sustainable chemical industry. However, cellulose from lignocellulose is not soluble in polar solvents, and is, therefore, difficult to convert into value added chemicals. A strategy to overcome this drawback is the use of mesoporous carbon, which enhances the affinity between the cellulose and the catalyst through its abundant functional groups and large uniform pores. Herein, we report on the preparation of a Pt catalyst supported on a type of 3D mesoporous carbon inspired by Echinometra mathae (Pt/CNE) to enhance the interaction between the catalyst and a nonsoluble reactant. In the hydrolytic hydrogenation of cellulose, the abundant oxygen groups of CNE facilitated the access of cellulose to the surface of the catalyst, and the open pore structure permits cello-oligomers to effectively diffuse to the active sites inside the pore. The highly dispersed Pt performed dual roles: hydrolysis by in situ generating protons from H2 or water as well as effective hydrogenation. The use of the Pt/CNE catalyst resulted in an approximately 80 % yield of hexitol, the best performance reported to date. In direct conversion of hardwood powder, the Pt/CNE shows good performance in the production of sugar alcohols (23 % yield). We expect that the open-structured 3D carbon will be widely applied to the conversion of various lignocellulosic materials. PMID- 24227503 TI - [The praise of the leak: a tribute to Henri Laborit (1914-1995)]. AB - Henri Laborit (1914-1995) was a French military MD. He contributed to the discovery of an important molecule that has changed the face of psychiatry, namely chlorpromazine, which became the first drug in the class of first generation antipsychotics, which later led to the dopamine hypothesis of schizophrenia. He did not receive the Nobel Prize for this discovery, unlike Daniel Bovet who get the Nobel Prize for the discovery of antihistaminics. Henri Laborit is also the author of a book that has contributed to the popularization of neurosciences in France, "The Praise of flight" (1976). PMID- 24227504 TI - Major pulmonary resections by exclusive VTS. a first in Tunisia. AB - Although thoracoscopic surgery had been introduced in Tunisia since 1993, there were no anatomical resections performed that way. We report herein the first 3 cases of lobectomy performed by exclusive video-thoracoscopic surgery (VTS). Three female patients presenting with bronchiectasis (2 cases) and cystic adenomatoid malformation (1 case) have underwent a thoracoscopic lobectomy with different outcomes. PMID- 24227505 TI - Diagnosis and management of refractory celiac disease: a systematic review. AB - BACKGROUND: Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. AIM: To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. METHODS: Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. RESULTS: Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. CONCLUSION: Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies. PMID- 24227506 TI - [Sexual abuse in Ziguinchor, Senegal: epidemiology and management]. AB - AIMS: To determine the frequency of sexual abuse, establish the demographic profile and to evaluate the care of victims of sexual abuse in Ziguinchor. METHODS: That is a retrospective, descriptive study from February 1, 2008 to August 31, 2010, including all patients received in the Department of Gynecology and Obstetrics, Ziguinchor Regional hospital for sexual abuse. For each patient, data analyzed were sociodemographic data, characteristics of aggression, clinical implications and psychological support. The data were entered and analyzed using the Excel 2003 version. RESULTS: 50 cases of sexual abuse were collected on 4950 patients, a prevalence of 1%. The average age of victims was 13 years (range: 3 to 23 years). The abuse took place in the day in 60% of cases. The location was familiar to victims in 70% of cases. The notion of penetrative genital contact was reported in 74% of victims. Physical force or a weapon was used in 34% of cases. The offender was 30 years old in 86% and operated alone in 92% of cases. Half of the victims had consulted in the first 24 hours. Genital trauma was found in 82% of victims. Feelings of fear, shame, or anger was observed in 64% of patients. Antibiotic was prescribed in two-thirds of the victims as postexposure prophylaxis for HIV was performed in only five patients. Emergency contraception was prescribed in 34% of victims. Six pregnancies were recorded. Six patients had developed complications such as depressive syndrome, hysteria with severe epileptiform seizures, mood disorder and psychosis. A proportion of 26% of victims did not consider it necessary to have recourse to justice. CONCLUSION: The management of a victim of sexual abuse should not stop at a forensic evaluation. We must therefore endeavor to provide a solution to three important consultation which are medical care, legal and emotional. PMID- 24227507 TI - Gender difference in patients with hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma represents the fifth most common cancer worldwide and account for approximately 90% of primary liver cancer. Men have a higher prevalence than women; the sex ratio varies between 2:1 and 4:1, depending on the geographic region. AIM: To determine the influence of gender on the clinicopathologic characteristics and survival of patients with hepatocellular carcinoma. METHODS: A retrospective analysis of medical records was performed in 63 patients with hepatocellular carcinoma and their clinicopathologic features and survival were compared in relation to gender. The data was summarized by descriptive statistics and analysed with SPSS version 11.5. RESULTS: Among these patients, 36 were men (57.1%) with male-to female ratio of 2:1.5, the mean female age was 59.8 years (p=0.054). Serum albumin level was significantly lower in women (p=0.0061).The average size of the tumor was 45.8mm and the difference was not significant (p=0.638). Hepatocellular carcinoma was significantly more prevalent among 16 men with post viral B cirrhosis (p=0.04). The main reason for therapeutic abstention was multifocal character of the hepatocellular carcinoma. The median survival time (6.52 months) was not different between the 2 groups. CONCLUSION: At diagnosis, men were younger than women. The viral C etiology was statistically more frequent in women than in men. Hepatocellular carcinoma was more aggressive in male but median survival time was not significant between groups. Screening and early treatment can limit this problem. PMID- 24227508 TI - [Association between suicidal behaviour and cyclothymic temperament in patients with recurrent depressive disorder]. AB - BACKGROUND: Suicidal behaviour is a major health problem, particularly among patients with depressive disorders. AIMS: To determine the frequency of suicidal behavior among sample of patients with recurrent depressive disorder and to explore the relationship between suicidal behavior and cyclothymic temperament in these patients. METHODS: This was a cross-sectional study bearing on 98 patients (43 men and 55 women, mean age of 46.8 +/- 9.9 years) followed for recurrent depressive disorder according to the criteria of DSM-IV recruited during partial or complete recovery interval. Information about suicidal behavior was collected from medical records. Cyclothymic temperament (CT) was assessed using the cyclothymic subscale (21 items). Patients who had scores above the threshold score of 10 and were considered as cyclothymic (CT+ group) and other patients were considered non-cyclothymic (CT- group). RESULTS: History of suicide attempts were reported in 22.4% of patients. The mean number of previous suicide attempts was significantly higher among patients in the TC+ group (0.7 +/- 1.4) versus 0.2 +/- 0.6 for patients in the TC- group (p=0.01). Recurrent thoughts of death and suicide attempts in the last depressive episode, were significantly higher in the CT+ group, with a 57.5% versus 24.6% in the CT- group, (p=0.001) and 33.3% versus 10.7% in the TC- group (p=0.006). A multivariate analysis retained the TC as an independent factor associated with suicidal behavior, with two other factors: the young age of patients and the frequency of previous hospitalizations. CONCLUSION: Our findings the frequency of suicidal behavior and suggest the involvement of CT in the increased risk of suicide among patients with recurrent depressive disorder. PMID- 24227509 TI - [Cutaneous adverse drug reaction: prospective study of 118 cases]. AB - BACKGROUND: Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions. AIM: To describe the adverse cutaneous reactions, their epidemiologic characteristics as well as the different causative drugs through a prospective hospital study. METHODS: A 12 month prospective study was managed in our department of dermatology of the teaching hospital Hedi Chaker of Sfax. Requested information included patient characteristics (associated disorders), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). The diagnosis was based on a beam of clinical and anamnestic arguments. The drug imputability was evaluated according to the Begaud's French method. RESULTS: One hundred eighteen cases were collected. A prevalence of 1.08/100 among patients consulting in dermatology department was estimated. The macular and papular exanthema represented the most frequent clinical aspects (42 cases) followed by acute urticaria (23 cases), photosensitivity (19 cases) and fixed drug eruption (15 cases). Principal imputable drugs were antibiotics, mainly penicillins followed by analgesics and non-steroidal anti-inflammatory. CONCLUSION: Although it was monocentric, this study revealed a high frequency of drug-induced dermatitis with different clinical presentation. The high incidence of drug-induced dermatitis induced by antibiotics, analgesics and anti-inflammatory is due to their widespread use, often in self-medication. PMID- 24227511 TI - [Is BNP assay useful for the diagnosis of acute dyspnea in emergencies departments?]. AB - BACKGROUND: It would be interesting to the emergency doctor to have at his disposal a helpful diagnostic tool like brain natriuretic peptide (BNP). Such assay is simple, available and reliable. AIMS: To report our experience on the role of BNP in the etiological diagnosis of acute dyspnea (AD) in emergency room (ER) and to assess the cost-effectiveness ratio of such diagnosis strategy. METHODS: A prospective study conducted in the ER of Rabta university teaching hospital of Tunis, from March 1st to June 20th 2010, involving 30 consecutive patients presenting to the emergency for AD. All patients underwent echocardiography in their acute phase and benefited from the dosage of BNP during the first 4 hours. The echocardiography parameters were collected by a single operator who was unaware of the results of the BNP dosage. RESULTS: The mean age of patients was 72.8years with a sex ratio of 1.5. AD was of orthopnea type in 9 cases and stage III NYHA dyspnea in the other patients. Clinical and radiological signs of left heart failure were noted in 30% of cases. Ultrasound data have objectified systolic dysfunction in 4 cases, diastolic in 3 cases and systolic plus diastolic in 10 cases. The BNP levels were below 100 pg/ml in 10 cases with pulmonary origin of the AD. A BNP level between 100 and 400 pg/ml was noted in 3 cases. In our study, the clinical probability of AHF prior to performing the test was estimated at 53% and estimated at 100% after the BNP assay. The BNP assay has reduced the length of stay in the emergency department 4 to 5 days and saved nearly 50% of the cost of care per patient. CONCLUSION: The BNP assay, has allowed us to confirm the AHF all cases. Given the prognostic value and economic benefit of this test we recommend its use in ER of our country. PMID- 24227510 TI - [The announcement of the lung age it is a motivation to quit smoking?]. AB - BACKGROUND: Smoking represents an ever-increasing problem of public health in the world, the impact of which is actually rising. The majority of smokers wish to stop smoking one day. This fact is one of the major acts leading to a better health and wellbeing. In the eighties, the lung age was already mentioned by Morris and Temple, a further tool motivating tobacco cessation. AIM: To determine the lung age of a population of workers and to evaluate the impact of its announcement on the smoking behavior. METHODS: It is a prospective study realized during a year (November 2010-November 2011) in a wire enterprise LEONI in Sousse (Tunisia), during an intervention program. 35 adult smokers were concerned by our study. A measurement of the breathing function by "Neo6" and a calculation of the lung age were practiced on all smokers. RESULTS: 35 smoking men (mean +/- SD age of 36 +/- 7 years, 27 and 28 smokers have, respectively, a high socio-economic level and a high schooling level) were included. The number of daily cigarettes consumed was from 5 to 40. The measurement of the smokers' respiratory function by the "Neo 6" did not show a pulmonary function defect. The lung age was of 45 +/-13 years, significantly higher than the chronological age. The evaluation of the announcement of the lung age, realized one year after, showed that 8 among the 35 workers have stopped smoking and 7 smokers have reduced their tobacco consumption. CONCLUSION: Communicating the lung age results is an additional tool motivating tobacco cessation. PMID- 24227512 TI - [Laparoscopic management of ovarian masses during pregnancy]. AB - BACKGROUND: The diagnosis of an adnexal mass associated with pregnancy is increasingly common with the routine use of ultrasound during prenatal care. AIM: To assess the feasibility, advantages and limiting factors of laparoscopy in the management of ovarian masses during pregnancy. METHODS: Rretrospective study of a series of 34 pregnant women operated by laparoscopy for adnexal masses during a period of 14 years. RESULTS: The mean age of patients was 29 years. Fifty percent of patients were nulliparous. In 62% of cases, patients were asymptomatic. Laparoscopy was performed at a mean gestational age of 15 weeks. Open laparoscopy was performed in 58.8% of cases. Intraperitoneal cystectomy was performed in 28 cases (72%). In two cases (5 %), it was a borderline ovarian tumor requiring further surgery outside of pregnancy. Fetal loss was noted at a term of 16 weeks. CONCLUSION: Laparoscopic management of adnexal masses during pregnancy appears to be safe and reproducible procedure with few maternal and fetal complications. PMID- 24227513 TI - [Benefits of coronary revascularization in septuagenarian patients with acute coronary syndrome]. AB - BACKGROUND: Prognosis of acute coronary syndrome (ACS) in elderly patients is bleak. Also older people tend to receive less invasive treatment than younger patients. AIM: To analyze the impact of coronary revascularization on the mid term outcome of septuagenarian patients admitted with ACS. METHODS: We retrospectively studied 250 patients 70 years or older hospitalised for ACS between january 2006 to september 2010. RESULTS: This population was more likely to be male with mean age 74 years and 93 % of ACS were inaugural events (60% NSTEMI, 40% STEMI). Coronary angiograms showed complex coronary lesions with a high incidence of multivessel disease, bifurcation lesions, and calcified stenosis. Seventy-six patients were treated medically and 174 underwent percutaneous or surgical revascularization. At six-month clinical follow-up, major adverse cardiac events (MACE) were significantly higher in medically treated than revascularized patients (62% Vs 31.7%, P <0.001). Patients with invasive strategy have significantly higher event free survival rate comparing to those assigned to medical management (64% Vs 49.7%, p: 0.01). CONCLUSION: Our study confirmed the superiority of invasive strategy compared to medical treatment in septuagenarian patients with acute coronary syndromes. Advanced age should not exclude patients from invasive strategy with complete revascularization. PMID- 24227514 TI - [Effectiveness and acceptance of hydroxyurea in the treatment of severe forms of sickle cell disease: a prospective study of 65 cases]. AB - BACKGROUND: Sickle cell disease is a serious illness by its complications. For the severe forms, three therapeutic options are actually allowed: transfusion therapy, hydroxyurea and bone marrow transplantation. aim: To evaluate the contribution of hydroxyurea in the management of severe forms of sickle cell disease. methods: It is a prospective study carried out a period of 11 years in "Centre National de Greffe de Moelle Osseuse" of Tunis. They were 65 patients divided into 38 homozygote forms and 27 double heterozygous composite S/beta thalassemics. The mean age was 130 months. The failure criterion of the treatment was hospitalization duration more than 15 days/ patient / year or the occurrence of a severe complication of the disease. results: The main indications of hydroxyurea were the prevention of the recidivism of an acute chest syndrome in 8 cases, iterative painful crises, more than 3 events per year, in 53 cases and anemic forms of the disease in 4 cases. We have observed, a rapid and durable improvement in the clinical manifestations and a significant fall of the number of hospitalization days / patient/year from 25.2 days to 2.6 days (p<0.001). The treatment was well tolerated. The rates of foetal hemoglobin have significantly increased from 6.4 to 27.45 % (p<0.001), of hemoglobin from 7.6 to 9.4 g/dl(p<0.001), of the mean corpuscular volume from 80.3 to 99.1 fl (p<0.001), and a significant fall of the white blood cell rate from 15077 to 8170/mm3 (p<0.001), of polynuclear neutrophils from 8015 to 3509/mm3 (p<0.001), and reticulocytes from 693736 to 209837 /mm3(p<0.001) was observed.Ten patients were considered as treatment failure with a failure rate of 15.3%. The main failure etiology was represented with bad observance. CONCLUSION: Hydroxyurea has a favored place in management of severe forms of sickle cell diseases of the child. Carefully used, with frequent monitoring does not have problems in short range but acceptance studies on the long term mast be undertaken. PMID- 24227515 TI - [Esophageal atresia associated with hypertrophic pyloric stenosis]. PMID- 24227517 TI - A case of spontaneous rupture perforation of sarcomatoid carcinoma in the urinary bladder. PMID- 24227516 TI - [A train can hide another]. PMID- 24227518 TI - [Uterine carcinosarcoma]. PMID- 24227519 TI - [Carcinoma of the sigmoid colon: an unusual cause of fourniers gangrene]. PMID- 24227520 TI - Systemic lupus erythematosus and Hodgkin disease. PMID- 24227521 TI - Selective arterial embolization in case of bleeding in advanced cervical cancer. PMID- 24227522 TI - [Endovascular treatment of an aneurysm of the abdominal aorta secondary to Behcet's disease]. PMID- 24227523 TI - [Ectopic pregnancy under Implanon contraception: a case of encysted haematocele]. PMID- 24227524 TI - Internal iliac vein thrombosis: a rare and multifactor complication in Crohn's disease. PMID- 24227525 TI - Concha bullosa pyocele. PMID- 24227526 TI - Syntaxin11 serves as a t-SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes. AB - CTLs kill target cells via fusion of lytic granules (LGs) at the immunological synapse (IS). Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) function as executors of exocytosis. The importance of SNAREs in CTL function is evident in the form of familial hemophagocytic lymphohistiocytosis type 4 that is caused by mutations in Syntaxin11 (Stx11), a Qa-SNARE protein. Here, we investigate the molecular mechanism of Stx11 function in primary human effector CTLs with high temporal and spatial resolution. Downregulation of endogenous Stx11 resulted in a complete inhibition of LG fusion that was paralleled by a reduction in LG dwell time at the IS. Dual color evanescent wave imaging suggested a sequential process, in which first Stx11 is transported to the IS through a subpopulation of recycling endosomes. The resulting Stx11 clusters at the IS then serve as a platform to mediate fusion of arriving LGs. We conclude that Stx11 functions as a t-SNARE for the final fusion of LG at the IS, explaining the severe phenotype of familial hemophagocytic lymphohistiocytosis type 4 on a molecular level. PMID- 24227527 TI - High-energy collisional activation studied via angle-resolved translational energy spectra of survivor ions. AB - Angle-resolved translational energy spectroscopy has been applied to Cs4I + (3) ions that survived 8 keV collisions with a range of collision gas targets, including inert gases and deuterium. The experimental data comprise values of the translational energy loss DeltaTR as a function of the (laboratory-frame) scattering angle theta R for each collision gas under conditions such that single collision events dominated the scattering. The values of DeltaTR increase with theta R, in accordance with very general expectations. However for any value of theta R, the values of DeltaTR for helium and deuterium as targets were almost indistinguishable from one another but were at least five to six times larger than those for neon and all other collision gases. These data have been shown to be consistent with theoretical considerations based upon conservation of energy and linear momentum. Theoretical approaches include the simple "elasticlimit" model, which makes no mechanistic assumptions, and a particular "binary-model" theory, which excludes electronic excitation as a possibility. Both theories are consistent with the experimental data and interpret the surprisingly large values of DeltaTR for low-mass targets in terms of large recoil energies of the target required to ensure conservation of momentum. The most likely alternative candidate as sink for DeltaTR is internal excitation of the target, but this possibility was excluded in the present work by choosing DeltaTR values less than the lowest excitation energies of the inert gas targets. Moreover, such an interpretation cannot explain the similar results obtained using helium and deuterium, which were markedly different from those obtained for all other collision gases. PMID- 24227528 TI - Delayed dissociation spectra of survivor ions from high-energy collisional activation. AB - Collisional activation (CA) of large ions at kiloelectronvolt energies is accompanied by unexpectedly large losses of translational energy, which vary with the nature of the collision gas. Previous investigations have concentrated upon subsequent fragmentations occurring within a time window covering a few fis immediately following collision, using massanalyzed ion kinetic energy spectrometry. In the present work, survivor ions were selected for specified values of translational energy loss, and their internal energy contents assessed via their subsequent unimolecular fragmentation reactions within a later time window. Beam collimation was also applied when circumstances permitted to impose angular selection, thus minimizing cross talk between effects of collisional scattering and energy dispersion. It was shown that internal excitation of the reactant ion can account for only a small fraction of the observed loss of translational energy. The recoil energy of the target is thus the principal sink for the translational energy loss, since the latter was always chosen to be less than the lowest excitation energy of the target. This conclusion is shown to be consistent with theoretical models of the CA process. The practical implications of these conclusions for CA of large ions at kiloelectronvolt energies are discussed. PMID- 24227529 TI - Analysis and elimination of systematic errors originating from coulomb mutual interaction and image charge in Fourier transform ion cyclotron resonance precise mass difference measurements. AB - The effect of mutual Coulomb-mediated interactions between ions of two different mass-to-charge ratios (but equal ion cyclotron orbital radii) on their Fourier transform ion cyclotron resonance (FT/ICR) mass spectral frequency difference is derived analytically and measured experimentally. For a cylindrical ion trap, ion packets are modeled theoretically as infinitely extended lines of charge, and contributions to cyclotron frequency difference due to direct Coulomb repulsion between the lime charges as well as the forces arising from image charge induced on the trap electrodes by each line charge are calculated. A striking theoretical prediction is that the effect on ICR frequency difference of mutual Coulomb repulsion between ions in a mass doublet may be compensated by the image-charge effect. As a result, there is an optimal (calculable) ion cyclotron orbital radius at which the measured cyclotron orbital frequency difference between ions of two different mass-to-charge ratios is independent of mutual Coulomb-mediated interactions between the two components of the mass doublet! Moreover, if the two mass-doublet component ions are present in equal numbers, then the measured ion cyclotron orbital frequency difference is also independent of all Coulomb mediated interactions between the two types of ions! Thus, the single largest systematic error in measurement of mass difference in a mass doublet by FT/ICR mass spectrometry may be virtually eliminated by appropriate control of ICR orbital radius and/or by performing measurements at various relative abundance ratios and extrapolating to equal relative abundance of the two mass-doublet components. We report experimental tests and verification of these predictions for two different mass doublets: (3)He(+)/(3)H(+) (cylindrical trap at 4.7 Tesla) and (12)C(1)H 2 (+) /(14) N(+) (cubic trap at 7.0 Tesla). From the latter measurement, we determine the mass of atomic nitrogen as m((14)N)=14.003 074 014(19) u. PMID- 24227530 TI - High-efficiency surface-induced dissociation on a rhenium oxide surface. AB - We report on the high-efficiency surface-induced dissociation of benzene and cyclohexane polyatomic ions after scattering from a rhenium oxide surface with a kinetic energy of 5-290 eV. Rhenium oxide was prepared by directly heating a rhenium metal foil, under 10(-5) mbar partial oxygen pressure, at about 1000 K.Rhenium oxide is characterized by a very high work function of 6.4 eV and thus minimizes ion reneutralization probabilities. The catalytic combustion of surface organic impurities with oxygen ensures good long-term stability.We found that the surface-induced dissociation ion current is 70 times larger on rhenium oxide than on bare rhenium or stainless steel. Absolute scattered ion yields of about 50% were measured. The implications of surface-induced dissociation on mass spectrometry in supersonic molecular beams are mentioned. PMID- 24227531 TI - Amino acid sequence prerequisites for the formation of cn ions. AB - Ammo acid sequence prerequisites are described for the formation of c, ions observed in high-energy collision-induced decomposition spectra of peptides. It is shown that the formation of cn ions is promoted by the nature of the amino acid C-terminal to the cleavage site. A propensity for cn cleavage preceding threonine, and to a lesser extent tryptophan, lysine, and serine, is demonstrated where fragmentation is directed N-terminally at these residues. In addition, the nature of the residue N-terminal to the cleavage site is shown to have little effect on cn ion formation. A mechanism for cn ion formation is proposed and its applicability to the results observed is discussed. PMID- 24227532 TI - Low-mass ions produced from peptides by high-energy collision-induced dissociation in tandem mass spectrometry. AB - High-energy collision-induced dissociation (CID) mass spectrometry provides a rapid and sensitive means for determining the primary sequence of peptides. The low-mass region (below mass 300) of a large number of tandem CID spectra of peptides has been analyzed. This mass region contains several types of informative fragment ions, including dipeptide ions, immonium ions, and other related ions. Useful low-mass ions are also present in negative-ion CID spectra. Immonium ions (general structure [H2N=CH-R](+), where R is the amino acid side chain) and related ions characteristic of specific amino acid residues give information as to the presence or absence of these residues in the peptide being analyzed. Tables of observed immonium and reiated ions for the 20 standard amino acids and for a number of modified amino acids are presented. A database consisting of 228 high-energy CID spectra of peptides has been established, and the frequency of occurrence of various ions indicative of specific ammo acid residues has been determined. Two model computer-aided schemes for analysis of the ammo-acid content of unknown peptides have been developed and tested against the database. PMID- 24227533 TI - Gas-phase halo alkylation of C60-fullerene by ion-molecule reaction under chemical ionization. AB - Chemical ionization (CI) mass spectra of C60-fullerene were studied using 1,2 dibromoethane and 1,2-dichloroethane as CI reagents. The ion-molecule reaction between C60 and C2H4X(+) (X=Br and Cl) leads to the formation of (C60+C2H4X)(+) adducts. The collision-induced dissociation of the adducts reveal gas phase halo alkylation of C60-fullerence involving the C-C bond formation. PMID- 24227534 TI - Determination of polycyclic aromatic hydrocarbons by high-performance liquid chromatography-particle beam-mass spectrometry. AB - In this article, we report a high-performance liquid chromatography-particle beam mass spectrometric (HPLC-PB-MS) method for the determination of polycyclic aromatic hydrocarbons (PAHs). The PB interface consists of a concentric ultrasonic nebulizer with temperature-controlled desolvation chamber and a three stage momentum separator. The HPLCPB-MS method showed greater sensitivity for PAHs with molecular weights above 178 than for those PAHs with molecular weights below 178. The percent relative standard deviations for the determination of 0.5 ng chrysene, 1.0 ng dibenzo[a,h]anthracene, 1.0 ng benzo[g,h,i]perylene, and 2.5 ng coronene were 20%, 2.5%, 13.7%, and 6%, respectively. The detection limits at signal/noise = 3 were 0.2 ng for chrysene, 1.0 ng for dibenzo[a,h]anthracene, 0.5 ng for benzo[g,h,i]perylene, and 1.5 ng for coronene. PMID- 24227536 TI - Charting weight four times daily as an effective behavioural approach to obesity in patients with type 2 diabetes. AB - Although many obese people successfully lose weight by dieting and/or behavioural therapy, most of them subsequently regain the lost weight. Thus, new therapeutic strategies are required to maintain weight loss. We report a woman with type 2 diabetes and moderate obesity who succeeded in achieving good glycaemic control and long-term weight loss with weaning from insulin therapy, while charting her weight four times daily. This charting method might be useful for long-term maintenance of weight reduction in obese diabetic patients. Obese patients can monitor their irregular weight fluctuations produced by overeating and correct both their food intake and their lifestyle. Further studies, including randomized control trials, will be needed to confirm the efficacy of this approach in patients with type 2 diabetes. PMID- 24227538 TI - Relationship between peripheral artery disease and combined albuminuria and low estimated glomerular filtration rate among elderly patients with type 2 diabetes mellitus. AB - This study aimed at investigating the combined effects of albuminuria and reduced estimated glomerular filtration rate (eGFR) on peripheral artery disease (PAD) among elderly patients with diabetes. A total of 236 subjects were cross classified into four groups according to the presence or absence of albuminuria (urinary albumin creatinine ratio (ACR) >= 30 mg/g) and low eGFR (<60 mL/min/1.73 m2). Cardiovascular risk factors and the ankle-brachial index (ABI) were also assessed. After multivariate adjustment using logistic regression analysis, the odds ratios (OR) for prevalent PAD related to albuminuria with preserved eGFR, normoalbuminuria with low eGFR and albuminuria with low eGFR compared to normoalbuminuria with preserved eGFR were 1.10 [95% confidence interval (CI) = 0.43-2.79], 3.14 (95% CI = 1.20-8.22) and 3.87 (95% CI = 1.72-8.72), respectively. In conclusion, in elderly patients with type 2 diabetes, both normoalbuminuria with low eGFR and albuminuria with low eGFR are associated independently with PAD. PMID- 24227537 TI - The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus. AB - The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/beta-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of beta catenin activity in the vascular cells. PMID- 24227539 TI - Marketing cigarettes when all else is unavailable: evidence of discounting in price-sensitive neighbourhoods. AB - OBJECTIVE: Since price is both a key determinant of smoking and one of the few remaining marketing strategies available in countries without point-of-sale tobacco display, this study examines cigarette price variations in the Australian market and assesses whether those variations are consistent with price being used to increase or maintain smoking among price-sensitive groups. METHOD: An audit of 1739 tobacco retailers was used to collect variations in the price of the best selling Australian cigarette brand, as well as record retailer compliance with tobacco retailing legislation. We examined variation in pricing across outlet type, demographic variations (socioeconomic level, % in the area under 18 and % born in Australia), remoteness and retailer compliance with tobacco retailing legislation. RESULTS: Multipacks were offered by 27.8% of retailers, with the average pack price in a twin pack $1.32 (or 7.3%) cheaper than a single pack. Prices were significantly lower in some outlet types, in lower socioeconomic postcodes and in those with a higher percentage of people under 18. In contrast with other consumer goods, prices were lower (although not significantly so) outside major cities. CONCLUSIONS: The provision of substantial multi-pack discounts and lower prices in postcodes with a higher proportion of price sensitive smokers (young people and those from lower socioeconomic groups) is consistent with targeted discounts being used as a tobacco marketing strategy. The results support policy interventions to counter selective discounts and to require disclosure of trade-based discounts. PMID- 24227540 TI - Applying linguistic methods to understanding smoking-related conversations on Twitter. AB - INTRODUCTION: Social media, such as Twitter, have become major channels of communication and commentary on popular culture, including conversations on our nation's leading addiction: tobacco. The current study examined Twitter conversations following two tobacco-related events in the media: (1) President Obama's doctor announcing that he had quit smoking and (2) the release of a photograph of Miley Cyrus (a former Disney child star) smoking a cigarette. With a focus on high-profile individuals whose actions can draw public attention, we aimed to characterise tobacco-related conversations as an example of tobacco related public discourse and to present a novel methodology for studying social media. METHODS: Tweets were collected 11-13 November 2011 (President Obama) and 1 3 August 2011 (Miley Cyrus) and analysed for relative frequency of terms, a novel application of a linguistic methodology. RESULTS: The President Obama data set (N=2749 tweets) had conversations about him quitting tobacco as well as a preponderance of information on political activity, links to websites, racialised terms and mention of marijuana. Websites and terms about Obama's smoke-free status were most central to the conversation. In the Miley Cyrus data (N=4746 tweets), terms that occurred with the greatest relative frequency were positive, emotional and supportive of quitting (eg, love, and please), with words such as 'love' most central to the conversation. CONCLUSIONS: People are talking about tobacco-related issues on Twitter, and semantic network analysis can be used to characterise on-line conversations. Future interventions may be able to harness social media and major current events to raise awareness of smoking-related issues. PMID- 24227541 TI - Cigarette tax avoidance and evasion: findings from the International Tobacco Control Policy Evaluation (ITC) Project. AB - BACKGROUND: Decades of research have produced overwhelming evidence that tobacco taxes reduce tobacco use and increase government tax revenue. The magnitude and effectiveness of taxes in reducing tobacco use provide an incentive for tobacco users, manufacturers and others, most notably criminal networks, to devise ways to avoid or evade tobacco taxes. Consequently, tobacco tax avoidance and tax evasion can reduce the public health and fiscal benefit of tobacco taxes. OBJECTIVES: First, this study aims to document, using data from the International Tobacco Control Policy Evaluation Project (ITC), levels and trends in cigarette users' tax avoidance and tax evasion behaviour in a sample of 16 low-, middle- and high-income countries. Second, this study explores factors associated with cigarette tax avoidance and evasion. METHODS: We used data from ITC surveys conducted in 16 countries to estimate the extent and type of cigarette tax avoidance/evasion between countries and across time. We used self-reported information about the source of a smoker's last purchase of cigarettes or self reported packaging information, or similar information gathered by the interviewers during face-to-face interviews to measure tax avoidance/evasion behaviours. We used generalised estimating equations to explore individual-level factors that may affect the likelihood of cigarette tax avoidance or evasion in Canada, the USA, the UK and France. FINDINGS: We found prevalence estimates of cigarette tax avoidance/evasion vary substantially between countries and across time. In Canada, France and the UK, more than 10% of smokers reported last purchasing cigarettes from low or untaxed sources, while in Malaysia some prevalence estimates suggested substantial cigarette tax avoidance/evasion. We also found important associations between household income and education and the likelihood to engage in tax avoidance/evasion. These associations, however, varied both in direction and magnitude across countries. PMID- 24227542 TI - Immunohistochemical expression of RECK protein in placental membranes of the preterm delivery with and without chorioamnionitis. AB - OBJECTIVE: To compare the immunohistochemical expression of RECK protein in placental membranes of late preterm delivery in women with and without histologically proven chorioamnionitis. STUDY DESIGN: Fetal membranes were collected from women who had late preterm delivery with (n=8) and without (n=9) histologic chorioamnionitis. Immunohistochemistry for RECK protein was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 13.0 was used for statistical analysis. RESULTS: There was weaker immunohistochemical expression of RECK protein in placental membranes of women with histologic chorioamnionitis compared to control subjects (P=0.0498). CONCLUSIONS: Chorioamnionitis has an impact on immunohistochemical expression of RECK protein in placental membranes in late preterm delivery. PMID- 24227543 TI - Photonenergy-controlled symmetry breaking with circularly polarized light. AB - Circularly polarized light (CPL) is known to be a true chiral entity capable of generating absolute molecular asymmetry. However, the degree of inducible optical activity depends on the lambda of the incident CPL. Exposure of amorphous films of rac-alanine to tunable CPL led to enantiomeric excesses (ee) which not only follow the helicity but also the energy of driving electromagnetic radiation. Postirradiation analyses using enantioselective multidimensional GC revealed energy-controlled ee values of up to 4.2 %, which correlate with theoretical predictions based on newly recorded anisotropy spectra g(lambda). The tunability of asymmetric photochemical induction implies that both magnitude and sign can be fully controlled by CPL. Such stereocontrol provides novel insights into the wavelength and polarization dependence of asymmetric photochemical reactions and are highly relevant for absolute asymmetric molecular synthesis and for understanding the origins of homochirality in living matter. PMID- 24227544 TI - A functional evenness index for microbial ecology. AB - Microbial ecologists attempting to describe community structures through the use of synthetic parameters face enormous difficulties. These stem in part from the necessity of using standard taxonomic reference levels in a field where the species level is poorly defined. This paper presents an attempt to obviate this problem. A "functional evenness" index (E) is defined using information measures; it is based directly on the characteristics of the bacteria, as determined, for example, with the API 20B method. Comparisons of this index with classic structure indices, such as taxonomic evenness (Pielou) or systematic dominance (Hulburt), show that it behaves like an evenness index, while bypassing the taxonomic study required before computation of the classic indices. Its use is illustrated with samples of aerobic heterotrophic bacteria obtained from brackish lagoon sediments. PMID- 24227545 TI - Seasonal distribution of nitrifying bacteria and rates of nitrification in coastal marine sediments. AB - The distribution of nitrification potential (NP) with depth in sediment and season was investigated in a shallow sandy sediment (0.5 m water) and a deeper muddy sediment (17m water). In both sediments, nitrifying bacteria were present in the anoxic strata (oxygen penetration was 5 mm below the surface). The NP at 6 8 cm depth in the sediment was 50% and 10% of the surface NP at the sandy and muddy sediment, respectively. It is suggested that bioturbation and physical disturbance of the sediment were the most likely reasons for this distribution. The NP increased as sediment temperature decreased. This effect was less marked in the muddy sediment. It is concluded that during the summer, the numbers or specific activity of nitrifying bacteria diminished for the following reasons: There was decreased O2 penetration into the sediment and increased competition for O2 by heterotrophs; there was increased competition for NH4 (+) and there was inhibition by H2S. These effects counteracted the potentially higher growth rates and increased rates of NH4 (+) production at the elevated summer temperatures. The potential nitrification rates in the upper 1 cm, which were measured at 22 degrees C, were converted to calculated rates at the in situ temperature (Q10=2.5) and in situ oxygen penetration. These calculated rates were shown to closely resemble the measured in situ rates of nitrification. The relationship between the in situ rates of nitrification and the nitrification potential is discussed. PMID- 24227546 TI - Hydrogen as an electron donor for sulfate-reducing bacteria in slurries of salt marsh sediment. AB - Experiments with a Warburg respirometer showed that a sediment slurry consumed hydrogen from a hydrogen atmosphere, and this consumption was not due to the activity of methanogenic bacteria. The hydrogren uptake was inhibited by the addition of 20 mM molybdate. Further experiments with sediment slurry held in conical flasks under an atmosphere of nitrogen showed that hydrogen accumulated in the headspace when bacterial sulfate reduction was inhibited either by the addition of 20 mM molybdate or by low (<5 mM) sulfate concentrations in the slurry. Methanogenesis was stimulated in the presence of a hydrogen atmosphere or by the addition of 20 mM molybdate. The results confirmed that hydrogren was an important electron donor for sulfate-reducing bacteria present in the sediment. The stimulation of methanogenesis by molybdate could be explained in part by a competition for hydrogen between sulfate-reducing bacteria and hydrogen metabolizing methanogenic bacteria, but competition for another common substrate, possibly acetate, could also be significant. PMID- 24227547 TI - Effect of mineral composition on bacterial attachment to submerged rock surfaces. AB - A direct microscopic count technique employing fluorescein isothiocyanate stain was used to compare microbial colonization on the exposed surfaces of rocks and minerals suspended in several ponds for various time intervals. Hematitic sandstone was never colonized at a rate greater than limestone, but quartz was always colonized more rapidly than calcite. The use of single-crystal minerals (quartz and calcite) in a nested factor experiment showed that the effect of the minerals on colonization was statistically significant, but that differences among the immersion sites were also significant. Sandstone samples placed in a pond outflow accumulated microbial colonizers more rapidly than those placed in the still waters of the same pond. The results indicate that the composition of the mineral substrate, in concert with the immersion environment, controls the formation of primary slime layers in aquatic systems. PMID- 24227548 TI - Seasonal selection in a freshwater heterotrophic bacterial community. AB - The objective of this study was to determine if a seasonal selection could be demonstrated in the heterotrophic component of a freshwater bacterial community. Surface samples were taken at approximately monthly intervals covering an annual seasonal cycle, and counts were made of the numbers of bacteria capable of growing at each of 10 incubation temperatures from 0 degrees to 45 degrees C at 5 degrees C intervals. Evidence for seasonal selection was provided by a 6 degrees C shift in the mean temperature of the counts from the summer sample to the winter sample. The selection was even more evident when the number of organisms capable of growing at 10 degrees C and those capable of growing at 35 degrees C were compared over the seasonal cycle. The counts at these two incubation temperatures varied inversely to each other. Although a negligible number of organisms from a representative summer sample grew at 10 degrees C, 18% of the organisms from a representative winter sample grew at this temperature. The data of this study indicate that, although seasonal selection does occur, the magnitude of that selection is not great enough to permit the growth of bacteria during the coldest month to approach the levels of growth observed during the summer months. However, the selection appears to be adequate to permit significant activity during the spring and fall transition months. PMID- 24227549 TI - Activity of bacteriolytic enzymes adsorbed to clays. AB - Myxococcus virescens is able to produce extracellular bacteriolytic enzymes that are rapidly adsorbed on montmorillonite. These adsorbed enzymes are active and can be assayed by measuring the release of UV-absorbing materials in mixtures containingMicrococcus luteus cells. The activity of the clay-adsorbed enzymes is, however, considerably lower than that of the unadsorbed enzymes. Both unadsorbed and adsorbed enzymes have their maximum activity at approximately the same pH. At lower clay-enzyme concentrations, the activity is proportional to the concentration. If, however, increasing amounts of clay are added to a fixed volume of clay-enzyme suspension, the activity remains almost unchanged until a definite limit is reached, then the activity decreases rapidly. This limit was dependent only on the ratio of the amounts of enzyme and clay and not on the absolute concentration of the enzyme. The montmorillonite-adsorbed bacteriolytic enzymes fromM. virescens were not active against gram-negative bacteria, and no activity against purified cell walls fromM. luteus could be measured. Montmorillonite-adsorbed egg white lysozyme was not active onM. luteus cells. PMID- 24227550 TI - Protozoan grazing of bacteria in soil-impact and importance. AB - Interactions between bacteria and protozoa in soil were studied over 2-week periods in the field and in a pot experiment. Under natural conditions the total biological activity was temporarily synchronized by a large rainfall, and in the laboratory by the addition of water to dried-out soil, with or without plants. In the field, peaks in numbers and biomass of bacteria appeared after the rain, and a peak of naked amoebae quickly followed. Of the three investigated groups flagellates, ciliates, and amoebae-only populations of the latter were large enough and fluctuated in a way that indicated a role as bacterial regulators. The bacterial increase was transient, and the amoebae alone were calculated to be able to cause 60% of the bacterial decrease. The same development of bacteria and protozoa was observed in the pot experiment: in the presence of roots, amoebic numbers increased 20 times and became 5 times higher than in the unplanted soil. In the planted pots, the amoebic increase was large enough to cause the whole bacterial decrease observed; but in the unplanted soil, consumption by the amoebae caused only one-third of the bacterial decrease. PMID- 24227551 TI - Effects of epiphyton onPotamogeton crispus L. leaves. AB - Potamogeton crispus L. grows as a winter producing annual in the shallow lakes of the Pongolo Floodplain, South Africa. Colonization of leaves by algal and bacterial epiphytes, as seen by scanning electron microscopy, followed the established pattern of increasing diversity and density with leaf age. It was apparent from the micrographs that the primary and subsequent colonizers were present even after death of the host leaf. Cross sections of leaves, viewed by transmission electron microscopy, illustrated that bacterial attachment did not damage the surface of young leaves. There was, however, extensive inward swelling and disorganization of the epidermal walls, characteristic of a reaction to invasion by pathogens. In older leaves the swelling was also present in mesophyll cells, while bacteria had invaded and degraded the epidermal cell wall. The bacterial invasion was concomitant with signs of senescence, and in dead leaves the organisms had penetrated and degraded the epidermis and mesophyll cell walls. The epiphyton/ host relationship may therefore be considered necrotrophic with important consequences for the transfer of energy from producers to consumers during decomposition. PMID- 24227552 TI - Evaluation of membrane adsorption-epifluorescence microscopy for the enumeration of bacteria in coastal surface films. AB - We have evaluated a method for enumerating surface slick bacteria by combining a membrane adsorption procedure with epifluorescence microscopy. Various chemicals were investigated for their ability to enhance bacterial elution from the membrane filters. The results of the elution-epifluorescence method were compared to plate counts and to direct epifluorescence counts of the sampling membrane filters. In all tests, the elution-epifluorescence technique yielded significantly higher bacterial concentrations. PMID- 24227553 TI - Phosphoproteome analysis of Lotus japonicus seeds. AB - In this study, we report the first dataset of phosphoproteins of the seeds of a model plant, Lotus japonicus. This dataset might be useful in studying the regulatory mechanisms of seed germination in legume plants. By proteomic analysis of seeds following water absorption, we identified a total of 721 phosphopeptides derived from 343 phosphoproteins in cotyledons, and 931 phosphopeptides from 473 phosphoproteins in hypocotyls. Kinase-specific prediction analyses revealed that different kinases were activated in cotyledons and hypocotyls. In particular, many peptides containing ATM-kinase target motifs, X-X-pS/pT-Q-X-X, were detected in cotyledons. Moreover, by real-time RT-PCR analysis, we found that expression of a homolog of ATM kinase is upregulated specifically in cotyledons, suggesting that this ATM-kinase homolog plays a significant role in cell proliferation in the cotyledons of L. japonicus seeds. The data have been deposited to the ProteomeXchange with identifier PXD000053 (http://proteomecentral.proteomexchange.org/dataset/PXD000053). PMID- 24227554 TI - Drug-induced liver injury secondary to testosterone prohormone dietary supplement use. AB - Dietary supplementation has become progressively more prevalent, with over half of the American population reporting use of various products. An increased incidence of supplement use has been reported in the military especially within Special Operations Forces (SOF) where training regimens rival those of elite athletes. Federal regulations regarding dietary supplements are minimal, allowing for general advertisement to the public without emphasis on the potentially harmful side effects. Subsequent medical care for these negative effects causes financial burden on the military in addition to the unit?s loss of an Operator and potential mission compromise. This report reviews a case of an Operator diagnosed with drug-induced liver injury secondary to a testosterone prohormone supplement called Post Cycle II. Clinical situations like this emphasize the necessity that SOF Operators and clinicians be aware of the risks and benefits of these minimally studied substances. Providers should also be aware of the Human Performance Resource Center for Health Information and Natural Medicines Comprehensive Database supplement safety ratings as well as the Food and Drug Administration?s MedWatch and Natural Medicines WATCH, to which adverse reactions should be reported. PMID- 24227555 TI - Identification and management of bed bug infestations in austere environments. AB - Military forces have missions that send them all over the globe. With the reemergence of bed bugs worldwide, the possibility of Servicemembers encountering them has increased. Special Operations Forces are often sent to locations that may not have integrated pest management support. Knowing how to identify and manage a bed bug infestation, with and without proper equipment and supplies, may become necessary in the very near future. It is also important that Servicemembers are aware of how bed bugs travel, to prevent their dispersal back to the United States and into their barracks and homes. PMID- 24227556 TI - Rice-based electrolyte drinks more effective than water in replacing sweat losses during hot weather training and operations. AB - Heat-related injury presents significant threats to the health and operational effectiveness of Soldiers and military operations. In 2012, active component, U.S. Armed Forces experienced 365 incident cases of heat stroke and 2,257 incident cases of ?other heat injury.? Most of these occurred among recruit and enlisted personnel and most were under the age of 30. In conditioned military personnel, a rice-based oral rehydration solution was superior to water alone at maintaining body weight and, by inference, enabled Soldiers to better maintain their the state of hydration during prolonged exercise in high ambient temperatures. In view of the health risks associated with dehydration and their effects on training and operations, this study suggests that the consumption of beverages containing electrolytes and a rice-based carbohydrate is superior to the consumption of water alone in preventing dehydration and heat related illness. PMID- 24227557 TI - Tactical lighting in special operations medicine: survey of current preferences. AB - Success in Special Operations Forces medicine (SOFMED) is dependent on maximizing visual capability without compromising the provider or casualty position when under fire. There is no single ideal light source suitable for varied SOFMED environments. We present the results of an online survey of Special Operations Medical Operators in an attempt to determine strengths and weaknesses of current systems. There was no consensus ideal hue for tactical illumination. Most Operators own three or more lights, and most lights were not night vision compatible. Most importantly, nearly 25% of respondents reported that lighting issues contributed to a poor casualty outcome; conversely, a majority (50 of 74) stated their system helped prevent a poor outcome. Based on the results of this initial survey, we can affirm that the design and choice of lighting is critical to SOFMED success. We are conducting ongoing studies to further define ideal systems for tactical applications including field, aviation, and marine settings. PMID- 24227558 TI - Filling in the gaps of predeployment fleet surgical team training using a team centered approach. AB - BACKGROUND: Teamwork and successful communication are essential parts of any medical specialty, especially in the trauma setting. U.S. Navy physicians developed a course for deploying fleet surgical teams to reinforce teamwork, communication, and baseline knowledge of trauma management. METHOD: The course combines 22 hours of classroom didactics along with 28 hours of hands-on simulation and cadaver-based laboratories to reinforce classroom concepts. It culminates in a 6-hour, multiwave exercise of multiple, critically injured victims of a mass casualty and uses the ?Cut Suit? (Human Worn Partial Task Surgical Simulator; Strategic Operations), which enables performance of multiple realistic surgical procedures as encountered on real casualties. Participants are graded on time taken from initial patient encounter to disposition and the number of errors made. Pre- and post-training written examinations are also given. The course is graded based on participants? evaluation of the course. RESULTS: The majority of the participants indicated that the course promoted teamwork, enhanced knowledge, and gave confidence. Only 51.72% of participants felt confident in dealing with trauma patients before the course, while 82.76% felt confident afterward (p = .01). Both the time spent on each patient and the number of errors made also decreased after course completion. CONCLUSION: The course was successful in improving teamwork, communication and base knowledge of all the team members. PMID- 24227559 TI - The correlation of early hyperglycemia with outcomes in adult trauma patients: a systematic review. AB - BACKGROUND: Hyperglycemia is often treated in both acute and long-term settings and has recently garnered attention for its utility as a prognostic marker in traumatic injury. This could be of vital importance in Special Operations, as triage and disposition of trauma patients are often accomplished under less-than ideal conditions. Blood glucose levels are easily obtained, require inexpensive instruments, but are likely not routinely taken in the field for trauma patients. OBJECTIVE: The objective of this review was to systematically search available medical literature for early (within 48 hours of presentation) hyperglycemia in trauma patients and present the relevant data regarding prognosis in a qualitative fashion. SOURCES: A systematic review was conducted of published English language articles using PubMed/MEDLINE in addition to searching bibliographies. Search terms included hyperglycemia, trauma, and prognosis. STUDY ELIGIBILITY CRITERIA: Eligible analytical studies had an adult population, who had experienced a traumatic injury, with blood glucose measurements within the first 48 hours of care, and had prognostic end points such as morbidity measures (intensive care unit time, infection, length of stay, etc.) and/or mortality. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were appraised according to their design, size, population characteristics, definition of ?hyperglycemic? and ?normoglycemic,? and morbidity and mortality outcomes. RESULTS: We reviewed 104 studies. Ninety-five were identified from a PubMed/MEDLINE search, and an additional nine were from relevant citations and bibliographies. Eighty-seven studies were excluded; 17 articles met inclusion criteria and were analyzed for the review. Five were prospective in nature and 12 were retrospective reviews. Five studies analyzed patients with traumatic brain injury, and one study exclusively concerned burn patients. Sixteen of the studies found negative outcomes with early hyperglycemia. One study found no significant relationship between serum glucose measurements and mortality. LIMITATIONS: LIMITATIONS of this review included the use of one database and articles available online and in English. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There is strong evidence that early hyperglycemia is correlated with a worse prognosis in trauma patients. Providers at all levels could potentially use this information to aid in the triage and disposition of traumatic injury victims. PMID- 24227560 TI - Cutaneous leishmaniasis: the efficacy of nonantimony treatment in the austere environment. Using cryotherapy, thermotherapy, and photodynamic therapy as an alternative method of treatment. AB - The author provides a retrospective review of clinical trials evaluating cryotherapy, photodynamic therapy (PDT), and thermotherapy in the treatment of cutaneous Leishmania infestations. Current cutaneous leishmaniasis (CL) treatment is based primarily on antimony compounds such as meglumine antimoniate, sodium stibogluconate, ketaconozole, amphotericin B, and other similar compounds. All have potentially severe sideeffects and relatively narrow therapeutic windows (i.e., the minimum doses that are therapeutic and do not cause harm). Investigational modalities using heat and cold therapies were shown to have similar results compared with current treatment regimens. Combination therapies have also been investigated and are the standard of treatment in the United States. Although the current therapies are effective in the treatment of the trypanosomatid protozoan Leishmania parasite, some effective alternative modalities have been shown to have fewer serious side-effects compared with current medications. Investigational studies that were reviewed showed that whether used individually or as an adjunct to traditional therapies, alternative treatment methods proved to be equally efficacious in treating CL. Some investigational therapies, such as cryotherapy as the sole modality, approached 92% cure rate. Any of the three investigated alternatives (i.e., heat, cold, or photodynamic) are techniques that could be readily used by Special Operations Forces (SOF) medics during their operations in remote and/or austere regions of the world. PMID- 24227561 TI - Use of the LMA Supreme in the Special Operations Environment: A Retrospective Comparison of the LMA Supreme and King LT-D. AB - The purpose of this study is to evaluate the use of the LMA Supreme(r) (LAM) as a combat supraglottic airway for U.S. Special Operations Forces (SOF). It is imperative to continuously evaluate and compare existing management options for airway control as requirements and technologies change. Providing our Special Operators with the most advanced and reliable medical equipment is of the utmost importance, and it is our intention here to compare the LMA Supreme with the currently fielded King LT-D(r) (King Systems) to determine whether the LMA Supreme may be a viable alternative supraglottic airway. PMID- 24227562 TI - Needle thoracentesis decompression: observations from postmortem computed tomography and autopsy. AB - BACKGROUND: Needle thoracentesis decompression (NTD) is a recommended emergency treatment for tension pneumothorax. Current doctrine recognizes two suitable sites: the second intercostal space in the midclavicular line and the fourth or fifth intercostal space in the anterior axillary line. METHODS: A review was conducted of postmortem computed tomography and autopsy results in 16 cases where NTD was performed as an emergency procedure. RESULTS: In 16 cases with 23 attempted procedures, the outcome was confirmed in 17 attempts. In 7 placements, the catheter was in the pleural cavity; in 7 placements, the catheter never entered the pleural cavity; and in 3 placements, cavity penetration was verified at autopsy even though the catheter was no longer in the cavity. Success was noted in 6 of 13 anterior attempts and 4 of 4 lateral attempts, for an overall success rate of 59% (10 of 17). In the remaining 6 attempted procedures, a catheter was noted in the soft tissue on imaging; however, presence or absence of pleural cavity penetration was equivocal. All placements were attempted in the combat environment; no information is available about specifically where or by whom. CONCLUSION: NTD via a lateral approach was more successful than that via an anterior approach, although it was used in fewer cases. This supports the revision of the Tactical Combat Casualty Care Guidelines specifying the lateral approach as an alternative to an anterior approach. PMID- 24227563 TI - Point-of-Care Coagulation Testing for Trauma Patients in a Military Setting: A Prospective Study. AB - BACKGROUND AND OBJECTIVE: Almost 50% of military trauma patients who need transfusions develop a coagulopathy. Immediately treating this coagulopathy improves the patient?s prognosis. Field military hospitals often lack laboratory devices needed to diagnose a clinically significant coagulopathy and have limited blood product resources such as plasma. Point-of-care (POC) devices for the measurement of prothrombin time (PT) are available and have been tested in a variety of situations, including hemorrhagic surgery. The authors compared a POC device, the Coaguchek XS Pro (F. Hoffmann-La Roche Ltd., Basel, Switzerland), with laboratory measures for determining the PT in military trauma patients in a field hospital. METHODS: This single-center prospective study was designed to compare POC coagulation monitoring with traditional laboratory testing. It was conducted at the French military hospital located at Kabul International Airport. All patients with trauma injuries resulting from war operations were included. A blood sample was drawn immediately on admission. PT was determined both in the laboratory and with use of the Coaguchek XS pro. RESULTS: Forty patients with war trauma were enrolled during a 3-month period. The authors recorded 69 measurements. The two methods were correlated with a correlation coefficient of 0.78 (p < .001). The Bland-Altman plot showed a mean difference of 5.8% (95% confidence interval ?14.9% to 26.6%). Using a PT cutoff of 60%, POC had a sensitivity of 77.1% and a specificity of 94.1%. RESULTS from POC PT measurement were available within a mean of 25.8 minutes before laboratory measures. CONCLUSIONS: The Coaguchek XS Pro device can be used successfully in an austere environment without compromising its performance. PMID- 24227564 TI - Cessation of vital signs monitored during lethal hemorrhage: a Swine study. AB - INTRODUCTION: Two challenges of trauma triage are to identify wounded who are in danger of imminent death and to enable medics to determine if resuscitation is possible when making ?dead or alive? decisions on the battlefield. Hemorrhagic shock is the leading cause of death in combat injuries. The purpose of this study was to establish the sequence of vital sign cessation during lethal hemorrhage in swine. Our hypothesis was that brain electrical activity (electroencephalography [EEG]) and respiration are earlier indicators of imminent death than traditional modalities measured during triage, such as heart electrical activity (electrocardiography [ECG]) and blood pressure. METHODS: Lethal hemorrhage was induced in anesthetized Yorkshire pigs. Vital sign modalities measured were respiration, heart electrical activity (ECG), heart sound, blood pressure (systemic arterial pressure), and brain electrical activity (EEG). RESULTS: The sequence of vital sign cessation was (1) respiration, (2) brain electrical activity (EEG), (3) heart sound, (4) blood pressure, and (5) heart electrical activity (ECG). Cessation of respiration occurred at approximately the same time that brain electrical activity stopped (?flatlined?) for 2 seconds and then resumed briefly before cessation; cessation of heart electrical activity occurred almost 8 minutes later. CONCLUSIONS: A 2-second EEG flatline and final respiration are useful event markers to indicate an opportunity to prevent irreversible brain damage from lethal hemorrhage. Since the 2-second EEG flatline and final respiration occur about 8 minutes before cessation of heart electrical activity (ECG), EEG and final respiration are earlier indicators of imminent death. The use of deployable noninvasive brain monitors implementing these findings can be live-saving on the battlefield as well is in civilian environments. PMID- 24227565 TI - U.s. Military experience with junctional wounds in war from 2001 to 2010. AB - BACKGROUND: In 2012, we reported on junctional wounds in war, but only of the few injuries that were critically severe. OBJECTIVE: The purpose of the present study is to associate a wide range of junctional wounds and casualty survival over a decade in order to evidence opportunities for improvement in trauma care within a large healthcare system. METHODS: We retrospectively surveyed data from a military trauma registry. We associated survival and injuries at the junction of the trunk and appendages in the current war (2001 to 2010). RESULTS: The junctional injury rate rose 14-fold from 0%, its minimum in 2001, to 5%, its maximum in 2010. Of the 833 casualties with junctional injury in the study, the survival rate was 83%; its change was not statistically significant over time. Most casualties had severe extremity injuries and associated injuries of other body regions such as the face and head. CONCLUSIONS: Junctional injury is common, severe, disabling, and lethal. The findings of this study may increase awareness of junctional injury. Opportunities for improvement which we identified included further research on the future addition of junctional codes (such as neck diagnoses) in order to align research methods to clinical care. PMID- 24227566 TI - Management of Junctional Hemorrhage in Tactical Combat Casualty Care: TCCC Guidelines?Proposed Change 13-03. AB - The vast majority of combat casualties who die from their injuries do so prior to reaching a medical treatment facility. Although most of these deaths result from nonsurvivable injuries, efforts to mitigate combat deaths can still be directed toward primary prevention through modification of techniques, tactics, and procedures and secondary prevention through improvement and use of personal protective equipment. For deaths that result from potentially survivable injuries, mitigation efforts should be directed toward primary and secondary prevention as well as tertiary prevention through medical care with an emphasis toward prehospital care as dictated by the fact that the preponderance of casualties die in the prehospital environment. Since the majority of casualties with potentially survivable injuries died from hemorrhage, priority must be placed on interventions, procedures, and training that mitigate death from truncal, junctional, and extremity exsanguination. In response to this need, multiple novel and effective junctional tourniquets have recently been developed. PMID- 24227567 TI - Tactical emergency casualty care?pediatric appendix: novel guidelines for the care of the pediatric casualty in the high-threat, prehospital environment. AB - BACKGROUND: Active shooter events and active violent incidents are increasingly targeting civilians, placing children at heightened risk for complex and devastating trauma. The U.S. Department of Homeland Security has identified as a priority preparing domestic first responders to manage complex mass casualty incidents as a primary step in strengthening our medical system. Existing literature suggests that many prehospital providers are uncomfortable treating critically ill or injured pediatric patients and that there is a gap in the consistent provision of high-quality trauma care to these patients. The success of threat-based care developed by the military has led to an exponential rise in the familiarity and utilization of these concepts within certain specialized elements of civilian care. Evolution of these concepts is accelerating to meet the demands of the nonmilitary civilian environment through the formation and subsequent work of the Committee for Tactical Emergency Casualty Care (C-TECC). However, a gap remains in the available literature describing the application of these principles to specialized populations. METHODS: In the absence of an evidence-based set of guidelines for prehospital care of the pediatric casualty, the C-TECC sought to establish a set of peer-reviewed guidelines to serve as a foundation describing current best practices. The Pediatric Working Group (PWG) utilized the adult TECC guidelines as a starting point and identified a series of key questions regarding trauma interventions. The PWG conducted a standard PubMed search to identify key relevant or potentially relevant literature. The literature review was presented to the C-TECC Guidelines Committee for review and approval of recommended principles. RECOMMENDATIONS: Given the dearth of supporting literature on the subject, the TECC committee was purposefully conservative in the adaptation of the adult TECC guidelines to a pediatric standard. The guidelines highlight information tailored to the pediatric population and were designed to be a resource for individual agencies seeking guidance for high-threat operations. To our knowledge, the TECC Pediatric Appendix is the first published recommendation for the widespread use of tourniquets in pediatric hemorrhage. In addition, the Guidelines are meant to highlight gaps in trauma literature and stimulate discussion regarding future research in the area of prehospital care of the pediatric casualty. PMID- 24227568 TI - Tactical medicine in response to acts of terrorism. PMID- 24227569 TI - The application of regional anesthesia by the special forces medical sergeant. PMID- 24227570 TI - Pertussis. AB - BACKGROUND: Pertussis, a disease that has been well described since the Middle Ages, has a worldwide distribution and can infect all ages. It is caused by the gram-negative, pleomorphic bacillus Bordetella pertussis, which is transmitted from human to human via aerosolized droplets at close range. Descriptions such as the one-hundred day cough in Chinese and whooping cough in English, describe the severity of this disease seen in both the developed and the developing world. PMID- 24227571 TI - Erythema ab igne. AB - Erythema ab igne is a reticulated, erythematous, hyperpigmented dermatosis resulting from chronic mild to moderate heat exposure. The authors present two cases of erythema ab igne, one from a hot water bottle to treat chronic low back pain and another from a heated automobile seat. They review other reported etiologies and highlight scenarios in which military medical providers may encounter erythema ab igne. PMID- 24227572 TI - Mandibular gland components of european and africanized honey bee queens (Apis mellifera L.). AB - The composition of the five-component honey bee queen mandibular gland pheromone (QMP) of mated European honey bee queens was compared to those of virgin and drone-laying (i.e., laying only haploid unfertilized eggs that develop into males), European queens and Africanized mated queens. QMP of mated European queens showed significantly greater quantities of individual components than all queen types compared, except for a significantly greater quantity of 9-hydroxy (E)-2-decenoic acid (9-HDA) found in Africanized queens. Glands of European drone laying queens contained quantities intermediate between virgin and mated queens, reflecting their intermediate reproductive state and age. QMP ontogeny shifts from a high proportion of 9-keto-(E)-2-decenoic acid (ODA) in young unmated queens to roughly equal proportions of ODA and 9-HDA in mated queens. A biosynthetic shift occurs after mating that results in a greater proportion of 9 HDA, methylp-hydroxybenzoate (HOB), and 4-hydroxy-3-methoxyphenylethanol (HVA) production, accompanied by a decreased proportion of ODA. Africanized QMP proportions of ODA and 9-HDA were significantly different from European queens. A quantitative definition of a "queen equivalent" of QMP is proposed for the various queen types, and a standard queen equivalent for mated European honeybee queen mandibular gland pheromone is adopted as 200ug ODA, 80ug 9-HDA, 20ug HOB, and 2 ug HVA. PMID- 24227573 TI - Effects of nitrogen fertilization on secondary chemistry and ectomycorrhizal state of Scots pine seedlings and on growth of grey pine aphid. AB - Effects of nitrogen availability on secondary compounds, mycorrhizal infection, and aphid growth of 1-year-old Scots pine (Pinus sylvestris L.) seedlings were studied during one growing season. Seedlings were fertilized with nutrient solutions containing low, optimum, and two elevated (2 * and 4 * optimum) levels of NH4NO3. At the end of growing season foliar nitrogen concentration, needle biomass, needle length, water contents of needles, root collar diameter, and number of buds increased with enhanced nitrogen availability. Addition of nitrogen did not have effect on concentrations of monoterpenes in growing needles, but in mature needles significantly decreased concentrations of some individual and total monoterpenes were detected. In growing needles the concentrations of some individual resin acids decreased, and in mature needles concentrations of some individual and total resin acids increased with increased nitrogen fertilization. Higher numbers of resin ducts were found in mature needles with nitrogen fertilization. Nitrogen fertilization decreased total phenolic concentrations in growing and mature needles of the current year, but in needles of the previous year no significant differences occurred. Mycorrhizal infection was highest at medium (optimum and 2 * optimum) nitrogen fertilization levels. The relative growth rate (RGR) of grey pine aphid [Schizolachnus pineti (F.)] responded positively to the increase in foliar nitrogen content. However, the increase in aphid performance between optimum and the highest fertilization level was slight. This may indicate a deterring effect of resin acids on aphids. The results indicate that carbon/nutrient balance hypothesis fails to predict directly the effects of nitrogen availability on concentrations of carbon-based defensive compounds in mature foliage. Altered nitrogen supply affects allocation to secondary metabolites differently, depending on the developmental state of the plant and the biosynthesis pathway, cost of synthesis, and storage of compounds. PMID- 24227574 TI - Host-location kairomone fromPeriplaneta americana (L.) for parasitoidAprostocetus hagenowii (Ratzeburg). AB - Chemically mediated host location in the eulophid parasitoidAprostocetus hagenowii (Ratzeburg) was investigated. In Y-tube bioassays 77.6% of female parasitoids responded to aPeriplaneta americana (L.) ootheca; parasitoids did not respond to air with no volatile stimuli. Frass from adult cockroaches was as attractive as an ootheca. Bioassay of one ootheca equivalent of five lipid fractions (eluted with hexane and 1, 5, 10, and 30% ether in hexane) from silica gel column chromatography indicated that the active component was a hydrocarbon. Further separation and bioassay of oothecal hydrocarbons by AgNO3-impregnated silica gel column chromatography indicated that the biological activity was in one fraction. Gas chromatographic (GC) analysis of this fraction revealed a single peak; this peak was identified by researchers in 1963, 1969, and 1972 as (Z,Z)-6,9-heptacosadiene. Qualitative and quantitative GC analyses of total hydrocarbons from oothecae, frass, and adult females were essentially identical; 6,9-heptacosadiene was the dominant hydrocarbon from each source. The alkadiene was 37 times more abundant in frass than on the ootheca. The volatilization of the alkadiene from oothecae was demonstrated by aeration and trapping on Super Q adsorbent. The current study is the first evidence for biological activity of (Z,Z)-6,9-heptacosadiene, a major hydrocarbon component on adult female American cockroaches, on their oothecae, and in their frass. PMID- 24227575 TI - Response of xylem-feeding leafhopper to host plant species and plant quality. AB - Carneocephala floridana, an oligophagous leafhopper that inhabits the salt marshes along the coasts of Florida, utilizesBorrichia frutescens andSalicornia virginica (both herbs) as primary summer hosts, but uses two grasses,Distichlis spicata andSpartina alterniflora, during the winter. We tested whether the seasonal patterns of abundance and apparent host-switching byCarneocephala are related to plant quality. In laboratory experiments, nymphs ofCarneocephala reared on nonfertilized control plants of the two herbs produced adults that were similar in size to field-collected insects. OnlyCarneocephala raised at the lowest densities onSpartina andDistichlis from the highest fertilizer treatments produced adults similar in body mass to those reared on nonfertilizedBorrichia andSalicornia. ForDistichlis, superior quality (high foliar nitrogen) plants were able to mitigate the negative effect of nymphal crowding on adult body mass. However, laboratory fertilization regimes produced an extremely high foliar nitrogen content in the two herbs and the organic acid concentration in the xylem fluid ofBorrichia, the only host species suitable for xylem fluid extraction, increased 2.5- to 3-fold. Total amino acid concentration in the xylem fluid of fertilizedBorrichia decreased compared to nonfertilized plants.Carneocephala demonstrated reduced feeding efficiencies on high nitrogenBorrichia. Our results suggest thatCarneocephala prefers, and performs better on, plants with high nitrogen content up to a threshold, beyond which high nitrogen levels result in reduced leafhopper feeding rates and assimilation efficiencies. PMID- 24227576 TI - Stereoselective synthesis of dominicalure 1 and 2: Components of aggregation pheromone from male lesser grain borerRhyzopertha dominica (F.). AB - Dominicalure 1 (9a) and dominicalure 2 (9b), were synthesized by esterification of alpha,beta-unsaturated acids4a and4b with (S)-(+)-2-pentanol (8). The key step was the asymmetric reduction of 3-penten-2-one (5) to give the chiral intermediate6, which, upon diimide reduction, DNB derivatization, recrystallization, and hydrolysis, yielded8 in 63% ee. Acids4a and4b were prepared in a simple and efficient three-step synthesis with an overall yield of 54% and 62%, respectively, in stereoisomerically pure form. PMID- 24227577 TI - Towards a rapid near-infrared technique for prediction of resistance to sugarcane borerEldana saccharina walker (Lepidoptera: Pyralidae) using stalk surface wax. AB - Multiple regression predictive models based on data acquired by near-infrared (NIR) spectrophotometry suggest that stalk surface wax components contribute towards resistance toEldana saccharina Walker in sugarcane. At least 35 sugarcane clones of known resistance were required to calibrate a predictive model that accounted for approximately 54% of the variation in resistance toEldana. Wavelengths chosen in multiple regression models suggest that alcohols and carbonyls are important in the wax contribution. Through the use of wax fractionation and gas chromatography, a high alcohol/aldehyde ratio and shorter carbon chain length appears to be associated with resistance. The use of NIR in the screening of wild germplasm and the early screening of breeding material for resistance, without prior knowledge of the biochemical mechanisms involved, is an exciting prospect. However, cause-and-effect relationships remain to be shown. PMID- 24227578 TI - Role of cuticular hydrocarbons of aphid parasitoids in their relationship to aphid-attending ants. AB - Lysiphlebus cardui, the dominant aphidiid parasitoid of the black bean aphid,Aphis fabae cirsiiacanthoidis (Afc), on creeping thistle, is able to forage in ant-attended aphid colonies without being attacked by ants. Several behavioral observations and experimental studies led to the hypothesis thatL. cardui mimics the cuticular hydrocarbon profile of its host aphid. Chemical analysis of the cuticular extracts revealed that bothL. cardui and Afc exclusively possess saturated hydrocarbons:n-alkanes, monomethyl (MMA), dimethyl (DMA), and trimethyl alkanes (TMA). Comparison of the hydrocarbon profiles of parasitoid and aphid showed great qualitative resemblance between parasitoid and host:L. cardui possesses almost all host-specific compounds in addition to species-specific hydrocarbons of mainly higher molecular weight (>C30). However, there is a lesser quantitative correspondence between parasitoid and host aphid. Furthermore, we analyzed the cuticular hydrocarbon profile of another parasitoid of Afc,Trioxys angelicae. This aphidiid species is vigorously attacked and finally killed by honeydewcollecting ants when encountered in aphid colonies. Its cuticular hydrocarbon profile is characterized by the presence of large amounts of (Z)-11 alkenes of chain lenghts C27, C29, C31, and C33, in addition to alkanes and presumably trienes. The role of the unsaturated hydrocarbons onT. angelicae as recognition cues for aphid-attending ants is discussed. PMID- 24227579 TI - Effect of birch (Betula pendula) bark and food protein level on root voles (Microtus oeconomus): I. food consumption, growth, and mortality. AB - The effect of protein and birch bark powder (BBP) content of forage on food consumption and growth of root voles (Microtus oeconomus) was studied by feeding young voles with eight different diets for two weeks. Voles ate more when the protein content of forage was moderate (6%) or low (3%), and when BBP was added to the diets, as compared to a high (12%) protein diet without BBP addition. On high and moderate protein diets voles gained weight, whereas on low protein diets they lost weight. Addition of BBP caused reduced growth or weight loss. Consuming a diet with moderate (6%) protein and high BBP (20%) resulted in high mortality (9 of 10 died). These results show that root voles need at least 6% protein for growth and that the effect of birch bark depends on the protein content of the forage. PMID- 24227580 TI - Effect of birch (Betula pendula) bark and food protein level on root voles (Microtus oeconomus): II. detoxification capacity. AB - The effect of protein and birch bark powder (BBP) content of forage on detoxification capacity of root voles (Microtus oeconomus) was studied. Young voles were fed with eight different diets for two weeks. Individuals on low (3%) protein diets had significantly lighter livers and kidneys than those on moderate (6%) or high (12%) protein diets. Birch bark powder addition did not have significant effect on organ weight. Detoxification was significantly induced, apparently due to secondary compounds in BBP. The activity of ethoxyresorufin-O dealkylase (EROD) was high when protein content or BBP concentration in forage was high as compared to low protein diets or diets containing no BBP. Glucuronidation, on the other hand, was not induced by BBP. High BBP content caused serious physiological stress to the voles. The only individuals surviving were those capable of sufficiently allocating energy and protein to detoxification. PMID- 24227581 TI - Identification of presumed pheromone blend from australasian predaceous bug,Oechalia schellenbergii (Heteroptera: Pentatomidae). AB - Oechalia schellenbergii is one of the most common predatory insects in Australia and the islands of the South Pacific. Adult males of this predaceous "true bug" collected during March near Gatton, Queensland, Australia, had a pair of enlarged exocrine glands opening underneath their wings that presumably produce an attractant pheromone. The two major components of the secretion are 3 methylenehexyl acetate and 9-hydroxygeranyl diacetate [2,6-dimethyl-2(E),6(E) octadien-1,8-diol diacetate]. PMID- 24227582 TI - Mammalian exocrine secretions: X. constituents of preorbital secretion of grysbok,Raphicerus melanotis. AB - Using electron impact and chemical ionization mass spectrometry with methane and nitric oxide as reactant gases in conjunction with mass spectral analysis of the dimethyl disulfide derivatives of unsaturated constituents, 51 compounds have been identified in addition to the compounds previously found in the preorbital secretion of the grysbokRaphicerus melanotis. The compounds identified are saturated, monounsaturated, and diunsaturated alcohols and formates, saturated and monounsaturated aldehydes, saturated carboxylic acids,gamma- anddelta lactones, alkyl methyl sulfides, andbeta-hydroxyalkyl acetates. All of these compounds have unbranched structures. The constituent previously incorrectly identified as (Z)-5-tetradecen-1-ol, was found to consist of the coeluting (Z)-7- and (Z)-8-tetradecenols. PMID- 24227583 TI - Preservation of salicaceae leaves for phytochemical analyses: Further assessment. AB - The chemistry of the plant family Salicaceae has been of interest to researchers as diverse as chemical ecologists, chemosystematists, and paper chemists. Continuing the debate on proper methods for preservation of plant material prior to analysis, vacuum-drying was recently advocated, because freeze-drying may cause degradation of phenolic glycosides. This study was conducted to clarify the consequences of freeze-drying for foliar secondary chemicals and to evaluate the consequences of vacuum-drying for primary compounds (protein and carbohydrates). Leaves of quaking aspen (Populus tremuloides) were flash-frozen in liquid nitrogen and freeze-dried or vacuum-dried at room temperature. We then analyzed samples for levels of salicortin and tremulacin (phenolic glycosides), condensed tannins, nitrogen, soluble protein, sugars, and starch. Freeze-drying did not alter the concentrations of phenolic glycosides or tannins, relative to vacuum drying. Freeze-drying did cause a small and inexplicable decline in nitrogen and soluble protein. Vacuum-drying, however, reduced starch concentrations by 38%. We suggest that the vacuum-drying method be used in studies in which carbohydrates are of no interest. For studies measuring carbohydrates, however, freeze-drying is a better alternative, and should effect no changes in levels of secondary compounds if samples are not allowed to thaw during the drying process. PMID- 24227584 TI - Learning and sibling odor preference in juvenile arctic char,Salvelinus alpinus (L.). AB - The importance of learning for sibling odor preference in juvenile Arctic char was analyzed in the present study. Fish were reared in the following eight conditions: (1) communally with siblings for 15 months; (2) communally with siblings for 17 months; (3) in isolation since fertilization; (4) in isolation since fertilization and exposed to sibling scent during the whole rearing period; (5) in isolation since fertilization and exposed to sibling scent from time of free swimming; (6) in isolation since fertilization and exposed to sibling scent during the whole rearing period, except two months without scent until testing; (7) in isolation since fertilization and exposed to sibling scent from time of free swimming, except two months without scent until testing; and (8) communally with siblings followed by a two-month isolation until testing. Char were followed individually in a Y-maze (fluviarium test) with a video-computer-based image analysis system for 12 hr. Sibling-scented water was supplied to one lateral half of the test area and water from non-siblings on the opposite half. Isolated individuals without any preexposure to siblings showed no significant preference. Test fish reared with siblings and those that had been reared in isolation but exposed to sibling scent until testing preferred water conditioned by their own siblings. Isolated fish that had been exposed to sibling scent since fertilization, or since free swimming, followed by a two-month period with only pure water, showed no significant preference. Char isolated for two months after being communally reared preferred water scented by siblings. The results demonstrated that behavioral discrimination between siblings and nonsibling odors occurred after total isolation (isolated both from siblings and sibling odors) only in individuals that had been communally reared. This may suggest that social interactions are important for learning and long-term memory of sibling odors in Arctic char. PMID- 24227585 TI - Sex pheromone of tomato pestScrobipalpuloides absoluta (Lepidoptera: Gelechiidae). AB - The sex attractant ofScrobipalpuloides absoluta females is a 90:10 mixture of (3E,8Z,11Z)-3,8,11-tetradecatrien-1-yl acetate and (3E,8Z)-3,8-tetradecadien-1-yl acetate. Tetradecadienyl acetates bearing 8Z,11Z; 3E,8Z; and 3E,11Z double bonds were synthesized by stereospecific procedures; the mass spectral and gas chromatographic properties of the 3E,8Z isomer were found to be congruent with those of the tetradecadienyl acetate fromS. absoluta. In wind tunnel bioassays, a 10:1 mixture of synthetic (3E,8Z,11Z)-3,8,11-tetradecatrien-1-yl acetate and (3E,8Z)-3,8-tetradecadien-1-yl acetate was highly attractive toS. absoluta males. Interestingly, the presence of (8Z,11Z)-8,11-tetradecadien-1-yl acetate (10%) inhibited the response to (3E,8Z,11Z)-3,8,11-tetradecatrien-1-yl acetate completely. PMID- 24227586 TI - Effects of allelochemicals on plant respiration and oxygen isotope fractionation by the alternative oxidase. AB - The goal of this investigation was to determine the effects of allelochemicals on plant respiration that thereby may be responsible for their role in growth inhibition. We have tested the effects of juglone, quercetin, cinnamic acid, andalpha-pinene on respiration rates, and electron partitioning through the cytochrome and alternative respiratory pathways, by measuring on-line oxygen consumption and oxygen isotope fractionation in soybean cotyledon tissue. Cinnamic acid andalpha-pinene decreased the oxygen consumption rate and increased the relative partitioning of electron transport to the alternative pathway. Possible biochemical mechanisms of these effects are discussed. PMID- 24227587 TI - Attraction ofCeratitis capitata (Diptera: Tephritidae) flies to odor of coffee fruit. AB - On potted nonfruiting host trees in outdoor field cages, we evaluated attraction of released mature laboratory-cultured or wild-origin Mediterranean fruit flies (medflies) to odor of freshly picked fruit of host and nonhost plants. Odor of ripe intact or crushed coffee fruit (the presumed ancestral host of medflies) was significantly more attractive than odor of ripe intact or crushed fruit of five lower-ranking hosts and three nonhosts. Odor of crushed coffee fruit was significantly more attractive than odor of intact coffee fruit. Odor of ripe or near-ripe coffee fruit was significantly more attractive than odor of unripe coffee fruit. Immature females (without eggs) were significantly more attracted to odor of a proteinaceous food lure than to odor of ripe coffee fruit, whereas the reverse was true for mature females carrying a high egg load. In some trials, males proved as discriminating as females in favor of coffee fruit odor, but in several other trials males were less discriminating than females. Response patterns of mature laboratory-cultured females were similar to those of mature wild-origin females. In a field of coffee plants, attraction of natural population females was significantly greater to odor of ripe coffee fruit than to water but was not greater than attraction to odor of proteinaceous food. Findings are discussed in relation to potential use of synthetic volatiles of coffee or other host fruit in traps for monitoring or controlling medflies. PMID- 24227588 TI - Behavioral response of femaleHelicoverpa (Heliothis)armigera HB. (Lepidoptera: Noctuidae) moths to synthetic pigeonpea (Cajanus cajan L.) kairomone. AB - FemaleH. armigera moths are highly attracted by a steam distillate from pigeonpea plants, one of their main hosts. A mixture of six compounds, all sesquiterpenes (beta-caryophyllene,alpha-humulene,alpha-guajene,alpha-muurolene,gamma-muurolene, andalpha-bulnesene), mixed in the proportions as found in the steam distillate, elicited the same behavioral responses (oriented upwind flights and contacts with the odor source) as the steam distillate. Onlyalpha-bulnesene was attractive by itself, but still less than the whole mixture. In addition, the sesquiterpene mixture acts as an oviposition stimulant. Both behavioral responses, orientation and oviposition, are concentration dependent. Electrophysiological recordings from female and male antennae (EAG) showed the same qualitative and quantitative responses to each of the compounds of the sesquiterpene mixture. The EAG responses to the original steam distillate were higher and similar to chickpea kairomonal components, which were also tested. The pigeonpea sesquiterpene mixture and its individual components elicited weak EAG responses only. The response of the male antenna to female-produced pheromone components was in the same range as the pigeonpea steam distillate. PMID- 24227589 TI - Effect of predator odors on heart rate and metabolic rate of wapiti (Cervus elaphus canadensis). AB - We measured the heart rate (HR) and oxygen consumption ([Formula: see text]) of wapiti (Cervus elaphus canadensis) before, during, and after presentation of biologically irrelevant odors (pentane, thiophene, and a perfume), artificial predator odors (an ether extract of cougar feces, and PDT, a compound found in mustelid anal gland secretion), stale predator odors (dog feces and urine and fox urine, kept at ambient temperature for a few weeks), and fresh predator odors (wolf, coyote, and cougar feces and the odor of a dead coyote, kept frozen between collection and test). Overall, responses to odors were small compared to other stressful stimuli. Individual variability was high among scents and among wapiti, but two of the fresh predator odors (cougar and wolf feces) produced larger HR and[Formula: see text] responses than the other scents and were more often successful at producing responses. As a group, fresh predator odors produced larger tachycardias and elicited a larger number of significant HR responses than biologically irrelevant novel odors. although the two classes of odors did not differ in their effect on[Formula: see text]. Although several other studies have shown that ungulates have reduced feeding levels when their food is scented with predator odors, it is not clear if this is due to reduced palatability or antipredator behavior. This study is the first demonstration that a wild ungulate species reacted more strongly to predator odors than to other odors in a nonfeeding situation. PMID- 24227590 TI - Coronary angiogram classification of spontaneous coronary artery dissection. AB - Spontaneous coronary artery dissection (SCAD) is under-diagnosed and the true prevalence is underestimated. Unfortunately, SCAD is frequently missed on coronary angiogram since the arterial wall is not imaged with this test. Optical coherence tomography or intravascular ultrasound should be the true gold-standard to diagnose SCAD. Given the elusive angiographic diagnosis of SCAD and the lack of familiarity with angiographic variants of SCAD, a diagnostic algorithm and angiographic classification for SCAD is proposed in this article. PMID- 24227591 TI - ICO amplicon NGS data analysis: a Web tool for variant detection in common high risk hereditary cancer genes analyzed by amplicon GS Junior next-generation sequencing. AB - Next-generation sequencing (NGS) has revolutionized genomic research and is set to have a major impact on genetic diagnostics thanks to the advent of benchtop sequencers and flexible kits for targeted libraries. Among the main hurdles in NGS are the difficulty of performing bioinformatic analysis of the huge volume of data generated and the high number of false positive calls that could be obtained, depending on the NGS technology and the analysis pipeline. Here, we present the development of a free and user-friendly Web data analysis tool that detects and filters sequence variants, provides coverage information, and allows the user to customize some basic parameters. The tool has been developed to provide accurate genetic analysis of targeted sequencing of common high-risk hereditary cancer genes using amplicon libraries run in a GS Junior System. The Web resource is linked to our own mutation database, to assist in the clinical classification of identified variants. We believe that this tool will greatly facilitate the use of the NGS approach in routine laboratories. PMID- 24227592 TI - Gender, power, and intimate partner violence: a study on couples from rural Malawi. AB - Gender-based power imbalances are perhaps the most compelling underlying explanation for intimate partner violence (IPV) among women in sub-Saharan Africa. However, an overemphasis on female victimization results in an incomplete understanding of men's experiences as victims and the broader dyadic context in which violence occurs. This study examines the role of three domains of relationship power (power resources, processes, and outcomes) on sexual and physical IPV victimization in a unique sample of 466 young couples from Malawi. Two power resources were studied, namely, income and education level. Power processes were captured with a measure of couple communication and collaboration called unity. Power outcomes included a measure of relationship dominance (male dominated or female-dominated/egalitarian). Multilevel logistic regression using the Actor Partner Interpersonal Model framework was used to test whether respondent and partner data were predictive of IPV. The findings show that unity and male dominance were salient power factors that influenced young people's risk for sexual IPV. Unity had a stronger protective effect on sexual IPV for women than for men. Involvement in a male-dominated relationship increased the risk of sexual IPV for women, but decreased the risk for men. The findings also showed that education level and unity were protective against physical IPV for both men and women. Contrary to what was expected, partner data did not play a role in the respondent's experience of IPV. The consistency of these findings with the literature, theory, and study limitations are discussed. PMID- 24227593 TI - DYT6 in Japan-genetic screening and clinical characteristics of the patients. PMID- 24227594 TI - Electron sharing and anion-pi recognition in molecular triangular prisms. AB - Stacking on a full belly: Triangular molecular prisms display electron sharing among their triangularly arranged naphthalenediimide (NDI) redox centers. Their electron-deficient cavities encapsulate linear triiodide anions, leading to the formation of supramolecular helices in the solid state. Chirality transfer is observed from the six chiral centers of the filled prisms to the single-handed helices. PMID- 24227595 TI - B-cell-derived IL-10 does not vitally contribute to the clinical course of glomerulonephritis. AB - IL-10-secreting regulatory B cells have been postulated as negative mediators of inflammation. However, their impact on immune-mediated diseases requires further investigation. We recently found that IL-10-secreting B cells infiltrate the kidney during crescentic glomerulonephritis (GN). We therefore studied the function of B-cell-derived IL-10 in light of the potential risks associated with increasingly used B-cell depleting therapies. Lack of IL-10 production by B cells, however, did not influence acute or adaptively mediated progressive renal injury in terms of renal function and histological damage in the nephrotoxic nephritis model of GN. Renal leukocyte infiltration and cytokine expression were similar apart from increased macrophages in mice lacking B-cell-derived IL-10. Systemic immune responses as assessed by cytokine production, leukocyte composition, proliferation, and activation were indistinguishable, while production and renal deposition of Ag-specific IgG were mildly impaired in the absence of B-cell-produced IL-10. Importantly, detailed analysis of systemic and renal regulatory T cells did not show any differences between nephritic mice bearing IL-10-deficient B cells and WT controls. Finally, studies in reporter mice revealed that B cells are only a minor source of systemic IL-10. In summary, our data reveal that endogenous B-cell-derived IL-10 does not play a major role in the nephrotoxic nephritis model of crescentic GN. PMID- 24227598 TI - Two-dimensional coulomb-induced frequency modulation in Fourier transform ion cyclotron resonance: A mechanism for line broadening at high mass and for large ion populations. AB - Fourier transform ion cyclotron resonance (FTICR) spectra generated for large ion populations exhibit frequency shifts and line broadening, apparently due to Coulomb forces between ions. Although previous two-dimensional (2D) models of Coulomb effects in FTICR accounted for frequency shifts, they did not account for spectral line broadening. In this article, a 2D model is proposed that predicts line broadening due to Coulomb-induced frequency modulation. The model considers the case of two different-mass ions orbiting at their respective cyclotron frequencies around a common guiding center. A mutual modulation of the cyclotron frequency occurs at the difference frequency between ions. If the modulation period is much shorter than the FTICR observation time, then sidebands spaced at intervals approximately equal to the modulation frequency are predicted. However, if the modulation period is similar in duration to the FTICR observation period, the sidebands can no longer be resolved, which results in spectral line broadening. This latter case is a necessary consequence for isotopic peaks in the high mass region around m/z 2000, where deterioration in FTICR performance has been observed. Computer simulations are used to confirm the mass dependence and to demonstrate other features of the model, including a strong dependence of the modulation on ion number. In support of the model, experimental FTICR spectra for large populations of methylnaphthalene ions at m/z 141 and 142 exhibit constant frequency sidebands corresponding to multiples of the difference frequency for the two ions extending from nominal values of m/z 136 to 147. PMID- 24227599 TI - Nonlinear resonance effects during ion storage in a quadrupole ion trap. AB - Contributions of higher-order fields to the quadrupolar storage field produce nonlinear resonances in the quadrupole ion trap. Storing ions with secular frequencies corresponding to these nonlinear resonances allows absorption of power from the higher-order fields. This results in increased axial and radial amplitudes which can cause ion ejection and collision-induced dissociation (CID). Experiments employing long storage times and/or high ion populations, such as chemical ionization, ion-molecule reaction studies, and resonance excitation CID, can be particularly susceptible to nonlinear resonance effects. The effects of higher-order fields on stored ions are presented and the influence of instrumental parameters such as radiofrequency and direct current voltage (qZ and az values), ion population, and storage time are discussed. PMID- 24227600 TI - Formation and emission of tetraalkylammonium salt molecular ions sputtered from a gelatin matrix. AB - A gelatin matrix was simultaneously doped with nine equimolar, homologous, tetraalkylammonium salts ranging in mass from 210 to 770 Da. Bombardment of the sample with kiloelectronvolt ions resulted in a nonidentical distribution of relative cation intensities with a maximum at m/z 242 for samples with a total salt concentration of 0.004 g of salt/g of gelatin. A rapid increase in relative intensities with increasing mass is observed for the low mass salts and is believed to be linked to changes in the ionization efficiencies. The changes in ionization efficiencies are likely related to decreasing coulombic attractive forces between the organic cation and the counterion. Disappearance cross sections, determined from decay curves, indicate that sputter-induced damage increases with increasing mass of the cation. Fragment-to-intact cation ratios also suggest that damage accumulates fastest in the heaviest salts. These observations indicate that desorption yields of the organic salts in a gelatin matrix decrease with increasing mass. In addition, suppression of lower mass tetraalkylammonium salt intact cation intensities was observed for salt-in gelatin concentrations greater than 10(-3) g/g. PMID- 24227601 TI - XeF(+), IF (+), and other unusual ions generated by reactions of hyperthermal ion beams at self-assembled monolayer surfaces. AB - Collisions of atomic and molecular ions (I(+), Xe(+); CH3I(+), I 2 (+) ) with self-assembled fluoroalkyl-monolayer surfaces result in reactions involving the net transfer of fluorine atoms or fluorocarbon radicals from the surface to the projectile ions. The scattered products, which include unusual ionic species such as IF(+), IF 2 (+) CFI(+); CF2I(+), I2F(+), and XeF(+), are generated in endothermic ion-surface reactions. These reactions are not observed when the collision partner is a gas-phase (rather than a surface-bound) perfluoroalkane. Evidence is presented which suggests that in some cases molecular projectiles undergo surface-induced dissociation to yield atomic species which subsequently react with the surface. Fluorine abstraction is favored for projectiles containing highly polarizable elements. PMID- 24227602 TI - Mechanism of gas-phase aldose-ketose isomerization: A study using tandem mass spectrometry and theoretical calculations. AB - Fast-atom bombardment tandem mass spectrometry and the semiempirical molecular orbital method were used to investigate the mechanism of gas-phase aldose-ketose isomerization process in lithiated 1,3 linked disaccharide isomers. Both the 1,3 hydrogen shift and hydride transfer mechanisms were investigated. Our experimental and theoretical calculations support the latter. The hydride transfer mechanism in these lithium-coordrnated systems is similar to the xylose isomerase catalyzed aldose-ketose isomerization. PMID- 24227603 TI - Oxidation reactions of dibenzothiophene subjected to negative chemical ionization with oxygen. AB - Dibenzothiophene (1) suffers surface-catalyzed oxidation under CI(O2) conditions. While in the positive mode M(+) is the only major ion and those of the oxidation products are of minor importance in the negative mode, essentially only ions stemming from oxidized species can be seen, the sulfone ion [M+O2](-) being the most important one. The ion m/z 184 previously attributed to M(-) is actually the anion of 2-sulfobenzoic acid cyclic anhydride. Structures for the various oxidation products are proposed and the mechanisms leading to their formation are discussed. PMID- 24227604 TI - Analysis of oligodeoxynucleotides by negative-ion matrix-assisted laser desorption mass spectrometry. AB - Thirty compounds were tested in combination with ammonium acetate for the ability to desorb and ionize oligodeoxynucleotides by ultraviolet matrix-assisted laser desorption mass spectrometry. Negative ion yields using matrices such as 2,5 dihydroxybenzoic acid and 3-hydroxy-4-methoxybenzaldehyde are enhanced by the addition of ammonium salts at a molar ratio of 1:1, pH 7. 3-Hydroxy-4 methoxybenzaldehyde was tested with 12 different ammonium, alkylammonium, and pyridinium salts for the ability to cocrystallize with oligodeoxynucleotides and to improve desorption and ionization. Ions of oligodeoxynucleotides 9, 10, and 11 nucleotides in length were observed with a matrix of 3-hydroxy-4 methoxybenzaldehyde and ammonium acetate, pH 7, at a mass resolution of 100-150 (fwhm). A small oligodeoxynucleotide (11-mer) was observed at the femtomole level with a combination of 2,5-dihydroxybenzoic acid and ammonium acetate as the matrix. Ions from single stranded DNA (60 nucleotides in length) were also observed using this same matrix combination. The results of these studies have shown that both sensitivity and desorption conditions need to be further improved before complex mixtures of large pieces of DNA can be effectively analyzed. PMID- 24227605 TI - Construction and characterization of a small-bore electrospray ionization source. AB - A simple, economical, and efficient electrospray ionization (ESI) source has been constructed in the configuration of a probe that makes use of a standard 13 mm vacuum lock. The principal components have been placed inside a glass tube making use of the electrical insulating properties of the glass while allowing for visual adjustments to be readily made. The ESI source, a variation of an atmospheric pressure ionization interface, is a modified version of designs published by Chait et al. (Rapid Comm. Mass Spectrom. 1990, 4, 81-87) and Knapp et al. (Annl. Chem. 1991, 63, 1658-1660) wherein a heated metal capillary is used for desolvation. The ESI probe has been tested on three different Extrel quadmpole mass spectrometers, with removable ion volumes, using polypeptides and small proteins. No modifications to the standard electron ionization/chemical ionization lens assembly were required to obtain excellent results other than removal of the ion volume. The spectra acquired were in excellent agreement with those previously published. PMID- 24227607 TI - Conference report : PDMS '93, Hirschegg, Kleinwalsertal, Austria, June 19-26, 1993. PMID- 24227606 TI - Laser desorption ion trap mass spectrometry of self-assembled monolayers. AB - It is demonstrated that laser desorption ion trap mass spectrometry (LD-ITMS) can be successfully applied to the chemical analysis of a monolayer of adsorbates on a solid surface. Negative ion spectra obtained from LD-ITMS of self-assembled monolayers adsorbed from solutions of alkanethiols (CH3(CH2)nSH with n=5, 9, and 15) onto polycrystalline gold surfaces displayed clear ion peaks corresponding to the sulfonate adsorbate species. Sulfonate ions with the general formula CH3(CH2)n SO3 were detected at m/z 165, 221, and 305, respectively, and were derived from the partial oxidation of the corresponding alkanethiol self assembled monolayers. Little fragmentation and no clustering was observed in these mass spectra. These results indicate that the sensitivity of LD-ITMS is sufficient to allow its application to a wide array of problems in surface science. PMID- 24227611 TI - Atomic model of the recognition site of the American cockroach pheromone receptor. AB - All the minimum-energy conformations (MECs) of two sex pheromones of the American cockroach,Periplaneta americana, and their 11 structural analogs (seven agonists, two antagonists, and two inactive compounds) were calculated using the molecular mechanics method. The MECs of the analogs were compared with the most populated MECs of the pheromones. The MECs most common in all the ligands were assumed to represent the bioactive conformations. An atomic model complementary to the bioactive conformation of one of the pheromones, periplanone B, was constructed. The model incorporates five groups capable of forming H bonds with oxygen atoms of the ligands and a set of hydrogen atoms contributing to nonbonded interactions with the ligands. Using this model, the energies of ligand-receptor complexes were calculated. For a group of mimics, the activities predicted from the calculated energies of ligand-receptor interactions were in reasonable agreement with the experimentally observed activities. The sites of the receptor model essential for the receptor activation were specified. PMID- 24227610 TI - Recognition memory and theta-gamma interactions in the hippocampus. AB - Neuronal oscillations and cross-frequency interactions in the rat hippocampus relate in important ways to memory processes and serve as a model for studying oscillatory activity in cognition more broadly. We report here that hippocampal synchrony (CA3-CA1 coherence) increased markedly in the low gamma range as rats were exploring novel objects, particularly those for which the rat subsequently showed good memory. The gamma synchrony varied across phases of the theta rhythm such that coherence was highest at the falling slope and trough of the theta wave. Further, the shape of the theta wave was more asymmetric and elongated at the falling slope during exploration of objects for which the rat subsequently showed good memory as compared with objects for which the rat subsequently showed poor memory. The results showed a strong association between event-related gamma synchrony in rat hippocampus and memory encoding for novel objects. In addition, a novel potential mechanism of cross-frequency interactions was observed whereby dynamic alterations in the shape of theta wave related to memory in correspondence with the strength of gamma synchrony. These findings add to our understanding of how theta and gamma oscillations interact in the hippocampus in the service of memory. PMID- 24227612 TI - Predator-induced diel vertical migration inDaphnia: Enrichment and preliminary chemical characterization of a kairomone exuded by fish. AB - Planktivorous fish release a cue of an unknown chemical nature into the water that induces diel vertical migration inDaphnia as predator avoidance response. We used a bioassay to obtain information about the chemical nature of the kairomone. We present a method to enrich the cue from holding water of fish by sorbent extraction. The kairomone exuded byLeucaspius delineatus can be characterized as a nonolefinic low-molecular-weight anion of intermediate lipophilicity. The presence of amino groups in the molecule can be excluded, whereas hydroxy groups are essential for activity. Separation by HPLC yielded only one active fraction. The kairomones released byCarassius carassius andRutilus rutilus showed the same chemical characteristics, suggesting that the kairomones from different species of fish, sensed byDaphia, are very similar, if not identical. PMID- 24227613 TI - Antifungal polyoxygenated fatty acids fromAeollanthus parvifolius. AB - Two polyoxygenated fatty acids with antifungal activity have been isolated from aerial parts ofAeollanthus parvifolius (Labiatae) using bioassay-guided isolation procedures. Spectroscopic analysis was used to identify the compounds as (Z) 4xi,9xi-diacetoxy-6xi,7xi-epoxy-5xi-hydroxy-8-oxododeca-2-enoic acid and (Z) 4xi,6xi,7xi,9xi-tetraacetoxy-5xi-hydroxy-8-oxododeca-2-enoic acid. Both of these compounds inhibited spore germination ofCladosporium cucumerinum. Minimum inhibitory doses were 1 ug and 5 ug, respectively, but only the former inhibited germination ofAspergillus niger at a dose of 5 ug. Neither compound exhibited antibacterial activity. (Z)-4xi,9xi-Diacetoxy-6xi,7xi-epoxy-5xi-hydroxy-8 oxododeca-2-enoic acid reduced the hyphal growth ofPythium ultimum. The mode of action was not resolved but did not involve either the disruption of the cell wall membrane or the inhibition of extracellular enzymes. Application of (Z) 4xi,6xi,7xi,9xi-tetraacetoxy-5xi-hydroxy-8-oxododeca-2-enoic acid to seedling plants did not give any protection against fungal attack, and indeed the compound appeared to be phytotoxic. PMID- 24227614 TI - Repellency of oral exudate to eastern and western spruce budworm larvae (Lepidoptera: Tortricidae). AB - A two-choice feeding bioassay was used to investigate the intra-specific repellency of the larval oral exudate of eastern and western spruce budworms,Choristoneura fumiferana (Clem.) andC. occidentalis Free., respectively. Results of the bioassay indicated that feeding behavior on artificial diet-drop feeding stations was modified in the presence of exudate, with feeding stations treated with conspecific exudate being avoided when an untreated station was available 3 cm away. Feeding was suppressed when a single, exudate-treated station was provided, or when the treated and untreated stations were separated by only 1 cm. The repellent effect functioned both inter- and intraspecifically. When induced to produce exudate,C. occidentalis larvae were not immediately repelled by either their own or other individuals' exudate. However, 24 hr after induction, test larvae were repelled by exudate from either source. In both species, larval oral exudate probably functions to repel conspecific competitors. PMID- 24227615 TI - Systemic induction of feeding deterrents in cotton plants by feeding ofSpodoptera SPP. Larvae. AB - Cotton,Gossypium hirsutum L., has been shown to exhibit systemic induced resistance to arthropods under certain conditions. We conducted experiments to determine the effects of previous feeding ofSpodoptera exigua Hubner andSpodoptera littoralis (Boisd.) larvae on feeding behavior, growth, and survival of larvae subsequently feeding on cotton. In one feeding choice test,S. exigua larvae preferred young leaves from undamaged control plants to undamaged young leaves from a previously damaged plant. Feeding deterrence was noticeable after only 6 hr of initial feeding damage by larvae, and there was almost complete deterrence after 30 and 54 hr of continuous feeding. In a second feeding choice test,S. littoralis larvae fed more on mature leaves from undamaged control plants than on undamaged mature leaves from previously damaged plants. In no choice tests, third instars ofS. littoralis fed undamaged young leaves from damaged plants did not gain weight and died by the seventh day, whereas larvae fed young leaves from undamaged control plants gained weight and pupated within 11 days. Sixth instars ofS. littoralis fed either old damaged leaves, old undamaged leaves, or young undamaged leaves all from previously damaged plants gained weight slowly and took more than 12 days to pupate, whereas larvae fed young leaves from undamaged plants gained weight rapidly and pupated within five days of the beginning of the experiment. PMID- 24227616 TI - Use of a comparative approach to identify allelopathic potential and relationship between allelopathy bioassays and "competition" experiments for ten grassland and plant species. AB - Various allelopathy bioassays were used to evaluate the allelopathic potential of 10 grassland forage species against a common test (phytometer) species,Carduus nutans L. Aqueous extracts did not influenceC. nutans germination, although radicle elongation was often severely inhibited.C. nutans was strongly affected by shoot, but not root, leachates. Decomposing ground tissue had mixed effects, and often stimulated shoot production ofC. nutans. Calculation ofR (2) (coefficient of determination) values between these results, and the results of previous experiments investigating the effects of the same 10 species onC. nutans emergence and development in field plots and glasshouse competition experiments frequently revealed strong, statistically significant relationships. Our results therefore provide correlative evidence for the importance of allelopathy in field conditions. PMID- 24227617 TI - Male sex pheromone of a giant danaine butterfly,Idea leuconoe. AB - Males of a giant danaine butterfly,Idea leuconoe, display hairpencils during courtship. The females were visually attracted to and olfactorily arrested by an artificial butterfly model to which male hairpencil extracts were added. The hairpencil extracts contained a complex mixture of volatiles, including pyrrolizidine alkaloid (PA) derivatives (danaidone, viridifloric beta-lactone), aromatics (phenol,p-cresol, benzoic acid), terpenoids (geranyl methyl thioether, (E,E)-farnesol), a series of gamma-lactones (6-hydroxy-4-undecanolides and its homologs), hydrocarbons [(Z)-9-tricosene, etc.], and several compounds with higher molecular weight. A mixture of the major volatiles applied to a butterfly dummy strongly elicited an abdomen-curling acceptance posture in females. Viridifloric beta-lactone and danaidone induced significant electroantennogram responses on the female's antennae, suggesting their principal role together with other hairpencil components as a sex pheromone to seduce females.I. leuconoe males seem to acquire the precursor for both of the PA fragments from the host plant,Parsonsia laevigata (Apocynaceae), during the larval stage; thereby they do not show pharmacophagous behavior towards PA-containing plants during the adult stage. However, males are pharmacophagously attracted to and feed on a number of simple phenolic compounds in a manner similar to other danaine species towards PAs. Wild males sequester one of the phagostimulants, (-)-mellein, in the hairpencils in varying quantities. Phenolic compounds incorporated in the hairpencils may act primarily as warning odors linked with the defensive PAs present in the body tissues. PMID- 24227618 TI - Effects of bilberry (Vaccinium myrtillus L.) litter on seed germination and early seedling growth of four boreal tree species. AB - Laboratory and greenhouse bioassays were used to test for inhibitory effects of senescent and decomposed leaves and aqueous extract from bilberry (Vaccinium myrtillus L.) against seed germination and seedling growth of aspen (Populus tremula L.), birch (Betula pendula Roth.), Scots pine (Pinus sylvestris L.), and Norway spruce [Picea abies (L.) Karst.]. Aqueous extracts from bilberry leaves were inhibitory to aspen seed germination and seedling growth and also induced root damage and growth abnormalities. Addition of activated carbon removed the inhibitory effects of extracts. Senescent leaves reduced pine and spruce seed germination, but rinsing of seeds reversed this inhibition. Senescent leaves were more inhibitory than decomposed leaf litter, suggesting that the inhibitory compounds in bilberry leaves are relatively soluble and released at early stages during decomposition. Spruce was generally less negatively affected by litter and aqueous extracts than the other tested species. This study indicates that chemical effects of bilberry litter have the potential to inhibit tree seedling recruitment, but these effects were not consistently strong. Phytotoxicity is unlikely to be of critical importance in determining success for spruce seedling establishment. PMID- 24227619 TI - Chemistry of metapleural gland secretions of three attine ants,Atta sexdens rubropilosa, Atta cephalotes, andAcromyrmex octospinosus (Hymenoptera: Formicidae). AB - The chemical composition of the secretions of the metapleural glands of workers and soldiers of twoAtta species,Atta sexdens rubropilosa andA. cephalotes, and workers ofAcromyrmex octospinosus, has been studied. As indicated by infrared spectrometry and confirmed by the ninhydrin test, the secretions contain chiefly proteins. Of the volatile acidic portion, which is present as ionized salts, phenylacetic acid is the major component in workers and soldiers ofA. s. rubropilosa andA. cephalotes. BothAtta species also contain 3-hydroxydecanoic acid and its homolog as minor components together with indoleacetic acid. While there are qualitative similarities in the acidic composition in the secretions ofA. s. rubropilosa andA. cephalotes, they differ quantitatively. The secretion ofAcromyrmex octospinosus contains 3-hydroxydecanoic and indoleacetic acids, but lacks phenylacetic acid. The bactericidal and fungicidal actions of the three major substances have been confirmed. PMID- 24227620 TI - Stable free radical from plant litter decomposing in water. AB - The presence of a stable radical species in both fresh straw and that which had been submerged in aerated water for up to six months has been demonstrated using electron paramagnetic (spin) resonance (EPR or ESR) spectroscopy. A radical signal was associated also with material shown to contain straw lignin markers, which was leached from the rotting straw into surrounding water. Fresh straw treated with strong alkali to remove phenolics did not show a radical signal. The possible effect of a dissolved stable free radical is discussed in relation to the antagonistic effect of rotting straw on algal and cyanobacterial growth in water to which straw has been added as a nuisance algal control agent. PMID- 24227621 TI - Pine needle oil causes avoidance behaviors in pocket gopherGeomys bursarius. AB - Essential oils from coniferous trees contain secondary metabolites that act as feeding deterrents for a number of herbivorous mammals. We investigated effects of pine needle oil on feeding and other behaviors of herbivorous plains pocket gophers. In experiment l, pocket gophers were offered sweet potato from single feeding stations placed in home cages of individually housed animals. Stations contained either a scent dispenser with pine needle oil or mineral oil. Subjects removed significantly less food from stations scented with pine needle oil. Experiment 2 was performed to investigate neophobic responses to odors.d Pulegone, presented under conditions identical to those used in experiment l, did not reduce food removal compared to mineral oil. In experiment 3 pocket gophers were observed in a maze consisting of a start box connected to two goal boxes by tunnels. One goal was scented with pine needle oil, the second with mineral oil. Subjects entered goals scented with pine needle oil significantly less frequently than goals scented with mineral oil and spent less time there. They performed all recorded behaviors at lower frequencies while located in pine-scented goals. In experiment 4 animals were introduced into a maze consisting of a start box from which two soil-packed tunnels could be entered. Embedded in the soil of one tunnel was a barrier of electrical cable that had been soaked in pine needle oil, the second tunnel contained a barrier of cable soaked in mineral oil. Pocket gophers gnawed significantly less insulation from cable treated with pine needle oil than from cable treated with mineral oil. Our results show that constituents in pine needle oil are aversive to plains pocket gophers. Under natural conditions they may function as feeding deterrents. Some of the compounds may be suitable repellents for control of pocket gopher damage. PMID- 24227622 TI - Chemiotropic behavior of female olive fly (Bactrocera oleae GMEL.) onOlea europaea L. AB - An interpretation is given of a number of observations on the chemiotropic behavior ofBactrocera oleae in connection with olive maceration water and the fly's return to the olive groves after the first summer rains. To this end, the headspace of both maceration water and leaf leaching water, simulating rainfall, were examined. In both cases, the presence of ammonia, which is generally known to attract fruit flies (Diptera, Tephritidae), was detected and, for the first time, in addition to other compounds that are inert for the fly, the presence of styrene was also detected. This aromatic hydrocarbon was found to be a strong attractant. It is shown that both ammonia and styrene are products of the metabolism of microbial flora present on the olive and leaf surface. PMID- 24227623 TI - Terpene variations in maritime pine constitutive oleoresin related to host tree selection byDioryctria sylvestrella RATZ. (Lepidoptera: Pyralidae). AB - Gas chromatographic analysis of the volatile terpenes of the wood oleoresin of maritime pines showed that the relative proportions of terpenes within the same tree did not vary according to sampling height and date. Pruning and tree vigor did not affect terpene profiles, but oleoresin composition varied widely from tree to tree. The trees attacked byDioryctria sylvestrella contained a significantly higher percentage of limonene, longipinene, and copaene, and a discriminant analysis, using the relative percentage of six terpenes, significantly separated infested and uninfested trees. The olfactory sensitivity of adult moths to a series of 20 volatile chemicals, including maritime pine oleoresin components, was evaluated with the electroantennogram method. Both sexes were sensitive to monoterpenes, oxygenated terpenoid compounds, and oleoresin samples. The use of terpenes as host attractants and biochemical markers for resistance toD. sylvestrella is discussed. PMID- 24227624 TI - Chemical defense of giant springtailTetrodontophora bielanensis (Waga) (Insecta: Collembola). AB - The giant springtail,Tetrodontophora bielanensis (Waga), is characterized by integumental openings (pseudocells) from which small droplets of a sticky defensive fluid are secreted after molestation. The secretion originates initially from secretory cells below the pseudocellae; subsequent irritations result in release of hemolymph, which was identified by both chemical and microscopical methods as well as by scanning electron microscopy. Bioassays with topically treated ground beetlesNebria brevicollis showed that the pseudocellular fluid evokes a total disorientation and cleansing behavior of the beetle. The main constituents were identified as the following pyridopyrazines: 2,3 dimethoxpyrido[2,3-b]pyrazine (1), 3-isopropyl-2-methoxypyrido[2,3-b]pyrazine (2), and 2-methoxy-4H-pyrido[2,3-b]pyrazine-3-one (3). These alkaloids are mainly present in the pseudocellar fluids of female and male springtails but are absent in their food or feces. Minor amounts are found in the hemolymph of adults, while larvae contain traces of2 only. All compounds were synthesized and tested for activity. In natural concentrations, the synthetic alkaloids elicited the same effects from the ground beetles as the pseudocellar fluid. PMID- 24227625 TI - Catalytic transfer hydrogenation/hydrogenolysis for reductive upgrading of furfural and 5-(hydroxymethyl)furfural. AB - The sequential transfer hydrogenation/hydrogenolysis of furfural and 5 hydroxymethylfurfural to 2-methylfuran and 2,5-dimethylfuran was studied over in situ reduced, Fe2 O3 -supported Cu, Ni, and Pd catalysts, with 2-propanol as hydrogen donor. The remarkable activity of Pd/Fe2 O3 in both transfer hydrogenation/hydrogenolysis is attributed to a strong metal-support interaction. Selectivity towards hydrogenation, hydrogenolysis, decarbonylation, and ring hydrogenation products is shown to strongly depend on the Pd loading. A significant enhancement in yield to 62%, of 2-methylfuran and 2 methyltetrahydrofuran was observed under continuous flow conditions. PMID- 24227626 TI - A combination of plaque components analyzed by integrated backscatter intravascular ultrasound and serum pregnancy-associated plasma protein a levels predict the no-reflow phenomenon during percutaneous coronary intervention. AB - AIMS: Previous studies reported that integrated backscatter intravascular ultrasound (IB-IVUS) provides high diagnostic accuracy for tissue characterization of coronary plaques and that pregnancy-associated plasma protein A (PAPP-A) could be a marker of adverse cardiac outcome in patients with cardiovascular disease. We examined whether IB-IVUS and PAPP-A levels could predict the incidence of no-reflow during percutaneous coronary intervention (PCI) METHODS AND RESULTS: About 176 consecutive patients (138 men, mean age 68 +/- 11 years) who underwent PCI with IB-IVUS were prospectively enrolled. Combined no-reflow, including transient filter no-reflow by using distal protection devices, was observed in 31 patients. The percentages of coronary lipid volume (%LV) analyzed by IB-IVUS and serum PAPP-A were significantly higher in patients with combined no-reflow than normal-reflow. To predict no-reflow, a receiver operating characteristic (ROC) analysis determined cut-off values of %LV as 62% and serum PAPP-A as 7.71 ng/mL. The multivariate logistic regression analysis showed that %LV (hazard ratio 4.5, 95% confidence interval 1.6-13.4, P < 0.01) and PAPP-A (hazard ratio 4.32, 95% confidence interval 1.5-12.7, P < 0.01) were independent predictors of combined no-reflow CONCLUSIONS: %LV analyzed by IB IVUS and serum PAPP-A levels were closely associated with the coronary no-reflow phenomenon. (c) 2014 Wiley Periodicals, Inc. PMID- 24227627 TI - NPHS2 mutations in steroid-resistant nephrotic syndrome: a mutation update and the associated phenotypic spectrum. AB - Mutations in the NPHS2 gene encoding podocin are implicated in an autosomal recessive form of nonsyndromic steroid-resistant nephrotic syndrome in both pediatric and adult patients. Patients with homozygous or compound heterozygous mutations commonly present with steroid-resistant nephrotic syndrome before the age of 6 years and rapidly progress to end-stage kidney disease with a very low prevalence of recurrence after renal transplantation. Here, we reviewed all the NPHS2 mutations published between October 1999 and September 2013, and also all novel mutations identified in our personal cohort and in international genetic laboratories. We identified 25 novel pathogenic mutations in addition to the 101 already described. The mutations are distributed along the entire coding region and lead to all kinds of alterations including 53 missense, 17 nonsense, 11 small insertions, 26 small deletions, 16 splicing, two indel mutations, and one mutation in the stop codon. In addition, 43 variants were classified as variants of unknown significance, as these missense changes were exclusively described in the heterozygous state and/or considered benign by prediction software. Genotype phenotype analyses established correlations between specific variants and age at onset, ethnicity, or clinical evolution. We created a Web database using the Leiden Open Variation Database (www.lovd.nl/NPHS2) software that will allow the inclusion of future reports. PMID- 24227628 TI - Unusual acetylation-dependent reaction cascade in the biosynthesis of the pyrroloindole drug physostigmine. AB - Physostigmine is a parasympathomimetic drug used to treat a variety of neurological disorders, including Alzheimer's disease and glaucoma. Because of its potent biological activity and unique pyrroloindole skeleton, physostigmine has been the target of many organic syntheses. However, the biosynthesis of physostigmine has been relatively understudied. In this study, we identified a biosynthetic gene cluster for physostigmine by genome mining. The 8.5 kb gene cluster encodes eight proteins (PsmA-H), seven of which are required for the synthesis of physostigmine from 5-hydroxytryptophan, as shown by in vitro total reconstitution. Further genetic and enzymatic studies enabled us to delineate the biosynthetic pathway for physostigmine. The pathway features an unusual reaction cascade consisting of highly coordinated methylation and acetylation/deacetylation reactions. PMID- 24227630 TI - Unilateral hyperhidrosis improved by subthalamic nucleus deep brain stimulation. PMID- 24227629 TI - Differential post-transcriptional regulation of IL-10 by TLR2 and TLR4-activated macrophages. AB - The activation of TLRs by microbial molecules triggers intracellular-signaling cascades and the expression of cytokines such as IL-10. Il10 expression is tightly controlled to ensure effective immune responses, while preventing pathology. Maximal TLR-induction of Il10 transcription in macrophages requires signaling through the MAPKs, ERK, and p38. Signals via p38 downstream of TLR4 activation also regulate IL-10 at the post-transcriptional level, but whether this mechanism operates downstream of other TLRs is not clear. We compared the regulation of IL-10 production in TLR2 and TLR4-stimulated BM-derived macrophages and found different stability profiles for the Il10 mRNA. TLR2 signals promoted a rapid induction and degradation of Il10 mRNA, whereas TLR4 signals protected Il10 mRNA from rapid degradation, due to the activation of Toll/IL-1 receptor domain containing adaptor inducing IFN-beta (TRIF) and enhanced p38 signaling. This differential post-transcriptional mechanism contributes to a stronger induction of IL-10 secretion via TLR4. Our study provides a molecular mechanism for the differential IL-10 production by TLR2- or TLR4-stimulated BMMs, showing that p38 induced stability is not common to all TLR-signaling pathways. This mechanism is also observed upon bacterial activation of TLR2 or TLR4 in BMMs, contributing to IL-10 modulation in these cells in an infection setting. PMID- 24227631 TI - Titanium-adhesive polymer nanoparticles as a surface-releasing system of dual osteogenic growth factors. AB - A titanium (Ti)-adhesive nanoparticle is developed as a surface-releasing system for dual osteogenic growth factors. The Ti-adhesive nanoparticle is prepared by self-assembly of a poly(L-lactide-co-glycolide) (PLGA)-grafted hyaluronic acid (HA) copolymer, followed by conjugation of catechol groups on nanoparticle surfaces. The nanoparticles consist of Ti-adhesive peripheral catechol groups, anionic HA shells, and hydrophobic PLGA inner cores. The immobilization of the nanoparticles onto Ti substrates is successfully verified using various analytical tools including field-emission scanning electron microscopy (Fe-SEM), contact angle measurement, and X-ray photoelectron spectroscopy (XPS). Positively charged dual growth factors, bone morphogenetic protein-2 (BMP-2) and insulin like growth factor-1 (IGF-1) are readily loaded onto the negatively charged HA shells of surface-immobilized nanoparticles, which is confirmed by fluorescence microscopy. The Ti substrates with dual growth factor-loaded nanoparticle immobilized nanoparticles remarkably promote the attachment, proliferation, spreading, and alkaline phosphatase (ALP) activity of human adipose-derived stem cells (hADSCs). PMID- 24227632 TI - Magnetic resonance imaging tracking of ultra small superparamagnetic iron oxide labeled rabbit dendritic cells. AB - Dendritic cells (DCs) play an important role in atherosclerosis plaque formation, but the mechanism has not been elucidated clearly. This study is designed to establish a method for tracing DCs in vivo facilitating the investigation of the DCs' specific roles in atherosclerosis. Rabbit DCs labeled by different concentrations of ultra small superparamagnetic iron oxide (USPIO) were injected into atherosclerosis rabbit model and traced with magnetic resonance imaging (MRI). Results showed that USPIO labeling nearly have no cytotoxicity to DCs in low concentrations (<500 ug/mL) but induced some decrease of cell viability at high concentrations (>500 ug/mL). Moreover, USPIO labeling, from 200 to 2000 ug/mL, caused a dose-dependent decrease of the mitochondrial membrane potential in DCs. The high labeling concentration (2000 ug/mL) triggered necrosis instead of apoptosis in DCs. By T2WI and fs T2WI sequence imaging comparison, DCs were found to exist in rabbit abdominal artery plaques after 24 h of transplantation and in spleen after one week detected by Prussian blue staining of tissue sections. We concluded that about 200 ug/mL USPIO is ideal to effectively label DCs for MRI tracing in vivo without a threat to cell viability. Combining USPIO labeling and MRI to track the movement of injected DCs in vivo is a feasible method. PMID- 24227633 TI - Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells. AB - Human mesenchymal stem/stromal cells (MSCs) have been explored in a number of clinical trials as a possible method of treating various diseases. However, the effect of long-term cell expansion in vitro on physiological function and genetic stability is still poorly understood. In this study, MSC cultures derived from bone marrow and liver were evaluated for the presence of aberrant cells following long-term expansion. In 46 independent cultures, four batches of transformed MSCs (TMCs) were found, which were all beyond the culture period of five weeks. These aberrant cells were first identified based on the appearance of abnormal cytology and the acquirement of growth advantage. Despite common MSC markers being diminished or absent, TMCs remain highly susceptible to lysis by allogenic natural killer (NK) cells. When transplanted into immunodeficient mice, TMCs formed sarcoma-like tumors, whereas parental MSCs did not form tumors in mice. Using a combination of high-resolution genome-wide DNA array and short-tandem repeat profiling, we confirmed the origin of TMCs and excluded the possibility of human cell line contamination. Additional genomic duplication and deletions were observed in TMCs, which may be associated with the transformation event. Using gene and microRNA expression arrays, a number of genes were identified that were differentially expressed between TMCs and their normal parental counterparts, which may potentially serve as biomarkers to screen cultures for evidence of early transformation events. In conclusion, the spontaneous transformation of MSCs resulting in tumorigenesis is rare and occurs after relatively long-term (beyond five weeks) culture. However, as an added safety measure, cultures of MSCs can potentially be screened based on a novel gene expression signature. PMID- 24227635 TI - Acute hemodynamic effects of a selective serotonin reuptake inhibitor in postural tachycardia syndrome: a randomized, crossover trial. AB - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are often prescribed in patients with postural tachycardia syndrome (POTS), and act at synaptic terminals to increase monoamine neurotransmitters. We hypothesized that they act to increase blood pressure and attenuate reflex tachycardia, thereby improving symptoms. Acute hemodynamic profiles after SSRI administration in POTS patients have not previously been reported. METHODS: Patients with POTS (n=39; F=37, 39 +/ 9 years) underwent a randomized crossover trial with sertraline 50mg and placebo. Heart rate, systolic, diastolic, and mean blood pressure were measured with the patient seated and standing for 10 min prior to drug or placebo administration, and then hourly for 4 h. The primary endpoint was standing heart rate at 4 h. RESULTS: At 4 h, standing heart rate and systolic blood pressure were not significantly different between sertraline and placebo. Seated systolic (106+/-12 mmHg vs. 101+/-8 mmHg; p=0.041), diastolic (72+/-8 mmHg vs. 69+/-8 mmHg; p=0.022), and mean blood pressure (86+/-9 mmHg vs. 81+/-9 mmHg; p=0.007) were significantly higher after sertraline administration than placebo. At 4 h, symptoms were worse with sertraline than placebo. CONCLUSIONS: Sertraline had a modest pressor effect in POTS patients, but this did not translate into a reduced heart rate or improved symptoms. PMID- 24227636 TI - A mixed microscopic method for differentiating seven species of "Bixie"-related Chinese Materia Medica. AB - Confusion in the species associated with the name of "Bixie" in Chinese Materia Medica began centuries ago. In recent decades, diverse medicinal plants from the genera Dioscorea and Smilax, and even minor species from the genus Heterosmilax, have been documented under the name Bixie or a very similar name as folk medicines in different areas of China. However, the traditional efficacies and chemical profiles of these herbs are not exactly the same and even vary wildly. Comprehensive authentication of multiple Bixie herbs has not yet been attempted. To differentiate and ensure the correct use of these Bixie-related herbs, in this study, seven sorts of representative Bixie herbs (Dioscorea collettii, D. zingiberensis, D. nipponica, D. septemloba, Smilax china, S. glabra, and Heterosmilax japonica) were characterized based on the microscopic examination of their powders and cryotomed transverse sections. This is not only the first attempt to distinguish Bixie herbs by a comprehensive microscopic techniques, including common light microscopy, fluorescence microscopy, and polarized light microscopy, but also it is the first research to observe characteristics of transections of crude drugs under polarized lighting for the purpose of authentication. Polarized light has been found to provide a number of unique characteristics. The results indicate that starch granules, stone cells, vascular bundles, and other significant tissue features can be used to authenticate "Bixie" herbs. The method was proven to be quick, handy, specific, and simple. It should be widely applicable to other herbal materials. PMID- 24227637 TI - Expert Panel Report: Guidelines (2013) for the management of overweight and obesity in adults. PMID- 24227634 TI - Fc gamma receptors in respiratory syncytial virus infections: implications for innate immunity. AB - RSV infections are a major burden in infants less than 3 months of age. Newborns and infants express a distinct immune system that is largely dependent on innate immunity and passive immunity from maternal antibodies. Antibodies can regulate immune responses against viruses through interaction with Fc gamma receptors leading to enhancement or neutralization of viral infections. The mechanisms underlying the immunomodulatory effect of Fc gamma receptors on viral infections have yet to be elucidated in infants. Herein, we will discuss current knowledge of the effects of antibodies and Fc gamma receptors on infant innate immunity to RSV. A better understanding of the pathogenesis of RSV infections in young infants may provide insight into novel therapeutic strategies such as vaccination. PMID- 24227638 TI - Special issues on Electrospray ionization. PMID- 24227639 TI - Ion formation from charged droplets: Roles of geometry, energy, and time. AB - The formation of ions from the charged droplets produced in the several spray ionization techniques is viewed as an activated rate process involving field assisted desorption, in accord with the ideas first set forth by Iribame and Thomson. The novel features of the present treatment are particularly relevant to the unique ability of electrospray ionization to transform large molecules in solution to free ions in the gas phase, with extensive multiple charging. These new features stem mainly from the realization that the spacing of charges on a desorbed ion must relate to the spacing of charges on the surface of the droplet whence it came. The consequences of this "rule" can account for the existence of maxima and minima in the number of charges on the ions of a particular species as well as the nature of the distribution of ions among the intervening charge states. They also explain the dependence of charge state on the configuration in solution of the parent molecule of the desorbed ion. In addition, they provide insight into the sequence in time at which ions in the various charge states leave an evaporating droplet. PMID- 24227640 TI - Observation and implications of high mass-to-charge ratio ions from electrospray ionization mass spectrometry. AB - High mass-to-charge ratio ions (> 4000) from electrospray ionization (ESI) have been observed for several proteins, including bovine cytochrome c (M r 12,231) and porcine pepsin (M r 34,584), by using a quadrupole mass spectrometer with an m/z 45,000 range. The ESI mass spectrum for cytochrome c in an aqueous solution gives a charge state distribution that ranges from 12 + to 2 +, with a broad, low intensity peak in the mass-to-charge ratio region corresponding to the [M + H](+) ion. the negative ion ESI mass spectrum for pepsin in 1% acetic acid solution shows a charge state distribution ranging from 7- to 2-. To observe the [M - H]( ) ion, harsher desolvation and interface conditions were required. Also observed was the abundant aggregation of the protens with average charge states substantially lower than observed for their monomeric counterparts. The negative ion ESI mass spectrum for cytochrome c in 1-100 mM NH4OAc solutions showed greater relative abundances for the higher mass-to-charge ratio ions than in acuidic solutions, with an [M - H](-) ion relative abundance approximately 50% that of the most abundant charge state peak. The observation that protein aggregates are formed with charge states comparable to monomeric species (at fower mass-to-charge ratios) suggests that the high mass-to-charge ratio monomers may be formed by the dissociation of aggregate species. The observation of low charge state and aggregate molecular ions concurrently with highly charged species may serve to support a variation of the charged residue model, originally described by Dole and co-workers (Dole, M., et al. J. Chem. Phys. 1968, 49, 2240; Mack, L. L., et al. J. Chem. Phys. 1970, 52, 4977) which involves the Coulombically driven formation of either very highly solvated molecular ions or lower ananometer-diameter droplets. PMID- 24227641 TI - Solvent effect on analyte charge state, signal intensity, and stability in negative ion electrospray mass spectrometry; implications for the mechanism of negative ion formation. AB - Department of Chemistry, University of New Orleans, New Orleans, Louisiana, USA The effect of solvent composition on negative ion electrospray ionization (ESI) mass spectrometry was examined. The onset potentials for ES1 of a series of chlorinated solvents and methanol were found to be within the range predicted by D. P. H. Smith, based on differences in the surface tension of the solvents used. The tendency toward electric discharge decreased with increasing percent weight of chlorine in the solvent. This effect has been attributed to an increasing propensity for electron capture for more highly chlorinated solvents. Addition of the electron scavenger gas SF, was even more effective at suppressing corona discharge phenomena. In a comparison of ultimate signal intensity obtainable for a test analyte in 10% methanol, the highest signal, which was stable over the widest range of temperatures, was exhibited by chloroform compared to dichloromethane, 1,2-dichloroethane, carbon tetrachloride, and methanol (100%). Chloroform, thus, is a recommended solvent for negative ion electrospray mass spectrometry (ES/MS) when solubility is not a limiting issue. Solvent polarity was shown to exhibit a profound influence on the distribution of charge states in negative ion ES/MS. For both chlorinated and nonchlorinated organic solvents, the higher the solution dielectric constant, the more the charge-state distribution is shifted toward higher charge states. These observations build on the "electrophoretic" mechanism of droplet charging. Solvents with high solution dielectric constants are considered to be most effective at stabilizing multiply charged ions (where charge separation is greatest), and they are likely to increase the level of droplet charging. Solvents with high basicities (gas phase and solution phase) and high proton affinities, yet low dielectric constants, favor lower charge states in ES mass spectra of lipid A and cardiolipin from Escherichia coli. This indicates that gas-phase processes and solvent basicity contribute much less toward ion formation than solution-phase solvation via preferred orientation of the solvent dipole. PMID- 24227642 TI - Fourier-transform electrospray instrumentation for tandem high-resolution mass spectrometry of large molecules. AB - Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, New York, USA Mass spectrometry instrumentation providing unit resolution and lo-ppm mass accuracy for molecules larger than 10 kDa was first reported in 1991. This instrumentation has now been improved with a 6.2-T magnet replacing that of 2.8 T, a more efficient vacuum system, ion injection with controlled ion kinetic energies, accumulated ion trapping with an open-cylindrical ion cell, acquisition of 2M data points, and updated electrospray apparatus. The resulting capabilities include resolving power of 5 * 10(5) for a 29-kDa protein, less than l-ppm mass measuring error, and dissociation of protein molecular ions to produce dozens of fragment ions whose exact masses can be identified from their mass-to-charge ratio values and isotopic peak spacing. PMID- 24227643 TI - High-resolution accurate mass measurements of biomolecules using a new electrospray ionization ion cyclotron resonance mass spectrometer. AB - A novel electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer based on a 7-T superconducting magnet was developed for high resolution accurate mass measurements of large biomolecules. Ions formed at atmospheric pressure using electrospray ionization (ESI) were transmitted (through six differential pumping stages) to the trapped ion cell maintained below 10(-9) torr. The increased pumping speed attainable with cryopumping (> 10(5) L/s) allowed brief pressure excursions to above 10(-4) torr, with greatly enhanced trapping efficiencies and subsequent short pumpdown times, facilitating high-resolution mass measurements. A set of electromechanical shutters were also used to minimize the effect of the directed molecular beam produced by the ES1 source and were open only during ion injection. Coupled with the use of the pulsed-valve gas inlet, the trapped ion cell was generally filled to the space charge limit within 100 ms. The use of 10-25 ms ion injection times allowed mass spectra to be obtained from 4 fmol of bovine insulin (Mr 5734) and ubiquitin (Mr 8565, with resolution sufficient to easily resolve the isotopic envelopes and determine the charge states. The microheterogeneity of the glycoprotein ribonuclease B was examined, giving a measured mass of 14,898.74 Da for the most abundant peak in the isotopic envelope of the normally glycosylated protein (i.e., with five mannose and two N-acetylglucosamine residues (an error of approximately 2 ppm) and an average error of approximately 1 ppm for the higher glycosylated and various H3PO4 adducted forms of the protein. Time-domain signals lasting in excess of 80 s were obtained for smaller proteins, producing, for example, a mass resolution of more than 700,000 for the 4(+) charge state (m/z 1434) of insulin. PMID- 24227644 TI - Negative ion formation in electrospray mass spectrometry. AB - Analytical and Chemical Sciences, Research Triangle Institute, Research Triangle Park, North Carolina, USA Negative ion electrospray (ES) operating on a single quadrupole mass spectrometer for the detection of low-molecular-weight molecules is discussed. The ES interface was operated at a positive cylindrical electrode potential to produce negative ions, and the results obtained were compared to the positive ion mode. As in the case of operation in the more common positive mode, negative ions with varying degrees of solvation and structurally relevant fragments can be obtained from a variety of solute species, including beta-lactam antibiotics, aminoglycosides, aminocyclitols, tetracyclines, sulfonamides, nucleotides, peptides, and explosives. No fragmentation of parent species, except those from some labile explosives, was provided because low potential differences are applied between the capillary and the first skimmer, and electrical discharge is avoided in the gas phase. An increase in the capillary voltage resulted in collision-induced decomposition to produce structurally relevant fragment ions in both operation modes. An evaluation of representative chromatographic solvents indicated that 2-propanol added with oxygen in the ES bath gas is best suited to suppress electrical (corona) discharge phenomena in negative ion operation, whereas it aids in solution nebulization, desolvation, and transfer of ions in solution to the gas phase. For positive ion mode, no such precaution was necessary. Conditions that promote the formation of ions in solution usually improve ES response. Therefore, an increase in the solvent pH can increase the sensitivity in negative ion ES ionization. Negative ion ES offers the advantage of providing complementary structural information to help in the characterization of an unknown compound or to confirm a certain tentatively proposed structure. Nucleotides and explosives were best characterized in negative ion mode owing to the ease with which they form anions in solution, and they could be detected down to the l-pg /gML level. PMID- 24227645 TI - Electrospray ionization mass spectrometry for analysis of low-molecular-weight anticancer drugs and their analogues. AB - In this study, several anticancer drugs and their analogues consisting of organic and organometallic compounds were analyzed by electrospray ionization mass spectrometry (ESI/MS) using a quadrupole mass spectrometer. Protonated molecular ions [M+H](+) were observed for all of the compounds studied, and in the case of the two steroid sulfates, deprotonated molecular ions [M-H](-) were obtained. Tandem mass spectrometry was performed on these quasimolecular ions, and the product ions formed provided useful fragmentation patterns that were characteristic for the compounds. This study provides evidence that ESI/MS is a sensitive technique for structure confirmation and identification of small organic and organometallic molecules. PMID- 24227646 TI - Applications of electrospray ionization mass spectrometry to neutral organic molecules including fullerenes. AB - The use of electrospray ionization mass spectrometry (ESI/MS) for the detection of neutral organic molecules becomes possible by their derivation with specific ESI/MS tagging reagents that have either proton or metal ion binding sites. We used the neutral crown ether group in several reagents to attach a metal binding site to substrate molecules. Application of this method to steroids, amino acids, vitamin D, fatty acids, and fullerenes is described. Besides characterization, tagged molecules can be used for studying organic reactions by ESI/MS. This work demonstrates that ESI/MS provides a unique window on fullerene solution chemistry. ESI/MS is not only an excellent tool for the analysis of biopolymers but is also useful for studying the organic chemistry of small neutral molecules. PMID- 24227649 TI - Erratum to: 10th asilomat conference on mass spectrometry: Time of flight mass spectrometry. PMID- 24227647 TI - Identification of components in waste streams by electrospray and tandem mass spectrometry. AB - Highly polar, non-gas-chromatographable compounds have few unambiguous analysis protocols for environmental applications. A recent environmental investigation, concerning the identification of a non-gas-chromatographable yellow component in chemical waste water and in effluents from a biological wastewater treatment plant required the use of a number of analytical approaches. Electrospray mass spectrometry, tandem mass spectrometry, high-performance liquid chromatography, nuclear magnetic resonance, and molecular spectroscopy of commercial and synthesized chlorodinitrophenol isomers were required in order to identify the specific isomer causing the color. The present report summarizes the electrospray ionization and tandem mass spectrometric studies that were used. The mass spectrometric study shows that two different isomers of chlorodinitrophenol exhibit very different collision-induced dissociation (CID) spectra. Differences in the tandem mass spectra can be attributed to the different structures of the anions formed from these two different isomers. Instrumentation that uses electrospray ionization and produces CID mass spectra and optical absorption spectra in a single analysis may be required in order to produce highly specific information on non-gas-chromatographable compounds found in the environment. PMID- 24227650 TI - Gold-catalyzed synthesis of tetrazoles from alkynes by C-C bond cleavage. PMID- 24227651 TI - A comparative study of P450 gene expression in field and laboratory Musca domestica L. strains. AB - BACKGROUND: The housefly is a global pest that has developed resistance to most insecticides applied for its control. Resistance has been associated with cytochrome P450 monooxygenases (P450s). The authors compare the expression of six genes possibly associated with insecticide resistance in three unselected strains: a multiresistant strain (791a), a neonicotinoid-resistant strain (766b) and a new field strain (845b). RESULTS: CYP4G2 was highly expressed throughout the range of strains and proved to be the one of the most interesting expression profiles of all P450s analysed. CYP6G4 was expressed up to 11-fold higher in 766b than in WHO-SRS. Significant differences between expression of P450 genes between F1 flies from 845b and established laboratory strains were shown. In general, P450 gene expression in 845b was 2-14-fold higher than in the reference strain (P < 0.0101) and 2-23-fold higher than in the multiresistant strain (P < 0.0110). CONCLUSION: The newly collected field strain 845b had significantly higher constitutive gene expression than both WHO-SRS and 791a. High constitutive expression of CYP4G2 in houseflies indicates a possible role of this gene in metabolic resistance. There is a strong indication that CYP6G4 is a major insecticide resistance gene involved in neonicotinoid resistance. PMID- 24227652 TI - COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons. AB - COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH) positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons. PMID- 24227653 TI - Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. AB - The Insm1 gene encodes a zinc finger factor expressed in many endocrine organs. We show here that Insm1 is required for differentiation of all endocrine cells in the pituitary. Thus, in Insm1 mutant mice, hormones characteristic of the different pituitary cell types (thyroid-stimulating hormone, follicle-stimulating hormone, melanocyte-stimulating hormone, adrenocorticotrope hormone, growth hormone and prolactin) are absent or produced at markedly reduced levels. This differentiation deficit is accompanied by upregulated expression of components of the Notch signaling pathway, and by prolonged expression of progenitor markers, such as Sox2. Furthermore, skeletal muscle-specific genes are ectopically expressed in endocrine cells, indicating that Insm1 participates in the repression of an inappropriate gene expression program. Because Insm1 is also essential for differentiation of endocrine cells in the pancreas, intestine and adrenal gland, it is emerging as a transcription factor that acts in a pan endocrine manner. The Insm1 factor contains a SNAG domain at its N-terminus, and we show here that the SNAG domain recruits histone-modifying factors (Kdm1a, Hdac1/2 and Rcor1-3) and other proteins implicated in transcriptional regulation (Hmg20a/b and Gse1). Deletion of sequences encoding the SNAG domain in mice disrupted differentiation of pituitary endocrine cells, and resulted in an upregulated expression of components of the Notch signaling pathway and ectopic expression of skeletal muscle-specific genes. Our work demonstrates that Insm1 acts in the epigenetic and transcriptional network that controls differentiation of endocrine cells in the anterior pituitary gland, and that it requires the SNAG domain to exert this function in vivo. PMID- 24227654 TI - Short-range Wnt5 signaling initiates specification of sea urchin posterior ectoderm. AB - The border between the posterior ectoderm and the endoderm is a location where two germ layers meet and establish an enduring relationship that also later serves, in deuterostomes, as the anatomical site of the anus. In the sea urchin, a prototypic deuterostome, the ectoderm-endoderm boundary is established before gastrulation, and ectodermal cells at the boundary are thought to provide patterning inputs to the underlying mesenchyme. Here we show that a short-range Wnt5 signal from the endoderm actively patterns the adjacent boundary ectoderm. This signal activates a unique subcircuit of the ectoderm gene regulatory network, including the transcription factors IrxA, Nk1, Pax2/5/8 and Lim1, which are ultimately restricted to subregions of the border ectoderm (BE). Surprisingly, Nodal and BMP2/4, previously shown to be activators of ectodermal specification and the secondary embryonic axis, instead restrict the expression of these genes to subregions of the BE. A detailed examination showed that endodermal Wnt5 functions as a short-range signal that activates only a narrow band of ectodermal cells, even though all ectoderm is competent to receive the signal. Thus, cells in the BE integrate positive and negative signals from both the primary and secondary embryonic axes to correctly locate and specify the border ectoderm. PMID- 24227655 TI - RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling. AB - The retinal pigment epithelium (RPE) is indispensable for vertebrate eye development and vision. In the classical model of optic vesicle patterning, the surface ectoderm produces fibroblast growth factors (FGFs) that specify the neural retina (NR) distally, whereas TGFbeta family members released from the proximal mesenchyme are involved in RPE specification. However, we previously proposed that bone morphogenetic proteins (BMPs) released from the surface ectoderm are essential for RPE specification in chick. We now show that the BMP- and Wnt-expressing surface ectoderm is required for RPE specification. We reveal that Wnt signalling from the overlying surface ectoderm is involved in restricting BMP-mediated RPE specification to the dorsal optic vesicle. Wnt2b is expressed in the dorsal surface ectoderm and subsequently in dorsal optic vesicle cells. Activation of Wnt signalling by implanting Wnt3a-soaked beads or inhibiting GSK3beta at optic vesicle stages inhibits NR development and converts the entire optic vesicle into RPE. Surface ectoderm removal at early optic vesicle stages or inhibition of Wnt, but not Wnt/beta-catenin, signalling prevents pigmentation and downregulates the RPE regulatory gene Mitf. Activation of BMP or Wnt signalling can replace the surface ectoderm to rescue MITF expression and optic cup formation. We provide evidence that BMPs and Wnts cooperate via a GSK3beta-dependent but beta-catenin-independent pathway at the level of pSmad to ensure RPE specification in dorsal optic vesicle cells. We propose a new dorsoventral model of optic vesicle patterning, whereby initially surface ectoderm-derived Wnt signalling directs dorsal optic vesicle cells to develop into RPE through a stabilising effect of BMP signalling. PMID- 24227657 TI - Establishing robust cognitive dimensions for characterization and differentiation of patients with Alzheimer's disease, mild cognitive impairment, frontotemporal dementia and depression. AB - OBJECTIVE: The diagnosis of mild cognitive impairment (MCI) and dementia requires detailed neuropsychological examinations. These examinations typically yield a large number of outcome variables, which may complicate the interpretation and communication of results. The purposes of this study were the following: (i) to reduce a large data set of interrelated neuropsychological variables to a smaller number of cognitive dimensions; (ii) to create a common metric for these dimensions (z-scores); and (iii) to study the ability of the cognitive dimensions to distinguish between groups of patients with different types of cognitive impairment. METHODS: We tested 1646 patients with different forms of dementia or with a major depression with a standard (n = 632) or, if cognitively less affected, a challenging neuropsychological battery (n = 1014). To identify the underlying cognitive dimensions of the two test batteries, maximum likelihood factor analyses with a promax rotation were conducted. To interpret the sum scores of the factors as standard scores, we divided them by the standard deviation of a cognitively healthy sample (n = 1145). RESULTS: The factor analyses yielded seven factors for each test battery. The cognitive dimensions in both test batteries distinguished patients with different forms of dementia (MCI, Alzheimer's dementia or frontotemporal dementia) and patients with major depression. Furthermore, patients with stable MCI could be separated from patients with progressing MCI. Discriminant analyses with an independent new sample of patients (n = 306) revealed that the new dimension scores distinguished new samples of patients with MCI from patients with Alzheimer's dementia with high accuracy. CONCLUSION: These findings suggest that these cognitive dimensions may benefit neuropsychological diagnostics. PMID- 24227656 TI - N-glycosylation requirements in neuromuscular synaptogenesis. AB - Neural development requires N-glycosylation regulation of intercellular signaling, but the requirements in synaptogenesis have not been well tested. All complex and hybrid N-glycosylation requires MGAT1 (UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyl-transferase I) function, and Mgat1 nulls are the most compromised N-glycosylation condition that survive long enough to permit synaptogenesis studies. At the Drosophila neuromuscular junction (NMJ), Mgat1 mutants display selective loss of lectin-defined carbohydrates in the extracellular synaptomatrix, and an accompanying accumulation of the secreted endogenous Mind the gap (MTG) lectin, a key synaptogenesis regulator. Null Mgat1 mutants exhibit strongly overelaborated synaptic structural development, consistent with inhibitory roles for complex/hybrid N-glycans in morphological synaptogenesis, and strengthened functional synapse differentiation, consistent with synaptogenic MTG functions. Synapse molecular composition is surprisingly selectively altered, with decreases in presynaptic active zone Bruchpilot (BRP) and postsynaptic Glutamate receptor subtype B (GLURIIB), but no detectable change in a wide range of other synaptic components. Synaptogenesis is driven by bidirectional trans-synaptic signals that traverse the glycan-rich synaptomatrix, and Mgat1 mutation disrupts both anterograde and retrograde signals, consistent with MTG regulation of trans-synaptic signaling. Downstream of intercellular signaling, pre- and postsynaptic scaffolds are recruited to drive synaptogenesis, and Mgat1 mutants exhibit loss of both classic Discs large 1 (DLG1) and newly defined Lethal (2) giant larvae [L(2)GL] scaffolds. We conclude that MGAT1 dependent N-glycosylation shapes the synaptomatrix carbohydrate environment and endogenous lectin localization within this domain, to modulate retention of trans synaptic signaling ligands driving synaptic scaffold recruitment during synaptogenesis. PMID- 24227659 TI - In vivo whole-brain T1-rho mapping across adulthood: normative values and age dependence. AB - PURPOSE: To report a systematic investigation of variations in brain T1rho (T1 rho) values over adulthood, and present normative values for cortical gray matter, juxtacortical white matter, selected white matter tracts and subcortical structures. MATERIALS AND METHODS: Forty-one healthy control subjects (23 males aged 18-76 years and 18 females aged 21-73 years) were imaged at 3.0 Tesla (T) using a novel whole-brain T1rho-weighted fluid suppressed three-dimensional turbo spin echo technique. T1rho maps were calculated and atlas-based segmentation used to determine regional T1rho values. Linear regression was used to determine changes in T1rho with age. RESULTS: T1rho values showed significant decreases with age in cortical gray matter (P < 0.001), left and right caudate (P = 0.004/0.006), putamen (P = 0.001, P < 0.001), hippocampus (P = 0.039/0.010), amygdala (P = 0.002/0.001), and nucleus accumbens (P = 0.001/0.002). Significant increases with age (P < 0.05) were observed in all the white matter tracts considered, except the corticospinal tracts and forceps major. CONCLUSION: T1rho demonstrates changes related to the processes of normal aging. PMID- 24227658 TI - Current Methods in Health Behavior Research Among U.S. Community College Students: A Review of the Literature. AB - The majority of health behavior research involving college students in the United States has focused on 4-year college students. Two-year or community college students have been less studied, although a significant proportion of U.S. undergraduates, primarily those from disadvantaged socioeconomic and/or racial/ethnic background, are enrolled in community colleges. Thus, there is a need to enhance health behavior and health promotion research among community college students. This study systematically reviewed 42 published, peer-reviewed health behavior studies conducted among U.S. community college students in order to determine the current state of research in the area with regard to behaviors studied, research designs used, recruitment and data collection strategies practiced, rates of student participation, and characteristics of the participants represented. Findings identified the methodological limitations of current research and suggested optimal recruitment and data collection methods suitable for various research needs. Findings are discussed in the context of enhancing health behavior research among U.S. community college students. PMID- 24227660 TI - Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. AB - OBJECTIVE: To evaluate the effects of canagliflozin, a sodium glucose co transporter 2 inhibitor, on body weight in overweight and obese subjects (body mass index [BMI] >=27 and <50 kg/m(2) ). METHODS: This 12-week, Phase 2b, randomized, double-blind study enrolled 376 subjects without diabetes mellitus who received canagliflozin 50, 100, or 300 mg or placebo once daily. The primary endpoint was the percent change in body weight from baseline through Week 12. RESULTS: Canagliflozin increased urinary glucose excretion in a dose-dependent manner and produced statistically significant reductions in body weight compared with placebo (least squares mean percent changes from baseline of -2.2%, -2.9%, 2.7%, and -1.3% with canagliflozin 50, 100, and 300 mg and placebo; P < 0.05 for all comparisons). Overall adverse event (AE) rates were similar across groups. Canagliflozin was associated with higher rates of genital mycotic infections in women, which were generally mild and led to few study discontinuations. Osmotic diuresis-related AE rates were low and similar across groups. CONCLUSIONS: In overweight and obese subjects without diabetes mellitus, canagliflozin significantly reduced body weight compared with placebo and was generally well tolerated. PMID- 24227661 TI - An open trial of 'grief-help': a cognitive-behavioural treatment for prolonged grief in children and adolescents. AB - In the past years, there is growing recognition of a syndrome of disturbed grief referred to as prolonged grief disorder (PGD). Although mostly studied in adults, clinically significant PGD symptoms have also been observed in children and adolescents. To date, no effective treatment for childhood PGD yet exists. We recently developed a nine-session cognitive-behavioural treatment for childhood PGD combined with five sessions of parental counselling. In the current article, we present outcomes of treatment of 10 consecutive children and adolescents turning to our university clinic with elevated PGD symptoms as their primary problem and main reason to seek therapy. Patients were significantly improved at post-treatment, with large improvements in self-rated PGD and post-traumatic stress (effect sizes > 0.8) and small to moderate improvement in depression and parent-rated internalizing and externalizing problems (0.2 < effect sizes < 0.8). Additional predictor analysis of outcomes suggested that, among other things, this treatment approach is less efficacious for children and adolescents further removed from loss and those confronted with suicidal loss. That said, the treatment appears promising, and controlled evaluation is clearly indicated. PMID- 24227662 TI - Asymmetric total synthesis of (+)-bermudenynol, a C15 Laurencia metabolite with a vinyl chloride containing oxocene skeleton, through intramolecular amide enolate alkylation. AB - A substrate-controlled asymmetric total synthesis of (+)-bermudenynol, a compact and synthetically challenging C15 Laurencia metabolite that contains several halogen atoms, is reported. The oxocene core, which contains a vinyl chloride, was constructed by an efficient and highly stereoselective intramolecular amide enolate alkylation (IAEA). This result showcases the broad utility of the IAEA methodology as a useful alternative for cases in which the ring-closing metathesis is inefficient. PMID- 24227663 TI - Special issues on electrospray ionization. PMID- 24227664 TI - Collision cross sections for protein ions. AB - A method for the determination of cross sections for gas-phase protein ions, based on the energy loss of ions as they pass through a collision gas, is described. A simple model relates the energy loss to the number of collisions and hence the cross section. Results from a Monte Carlo model that support the validity of this approach are described. Experimental cross sections are reported for motilin, ubiquitin, cytochrome c, myoglobm, and bovine serum albumin. Cross sections range from approximately 800 A(2) for motilin to approximately 14,000 A(2) for bovine serum albumin and generally increase with the number of charges on the ion. Cytochrome c ions from aqueous solution show somewhat smaller cross sections than ions formed from solutions of higher organic content, suggesting that the gas-phase ions may retain some memory of their solution conformation. PMID- 24227665 TI - Application of electrospray mass spectrometry in probing protein-protein and protein-ligand noncovalent interactions. AB - A novel mass spectrometry-based methodology using electrospray ionization (ESI) is described for the detection of protein-protein [interferon (IFN)-gamma dimer] and protein-ligand [ras-guanosine diphosphate (GDP)] noncovalent interactions. The method utilizes ESI from aqueous solution at appropriate pH. The presence of the noncovalent complex of the IFN-gamma dimer was confirmed by the observed average molecular weight of 33,819 Da. The key to the detection of the IFN-gamma dimer is the use of an alkaline solution (pH ~ 9) for sample preparation and for mass spectrornetry analysis. The effect of the declustering energy in the region of the ion sampling orifice and focusing quadrupole on the preservation of the gas-phase noncovalent complex (IFN-gamma dimer) was also studied. The effect of the declustering energy on complex dissociation was further extended to probe the noncovalent protein-ligand association of ras-GDP. It was found that little energy is required to dissociate the IFN-gamma dimer, whereas a substantial amount of energy is required to dissociate the gas-phase ras-GDP complex. PMID- 24227666 TI - Studies on heme binding in myoglobin, hemoglobin, and cytochrome c by ion spray mass spectrometry. AB - The ion spray mass spectra of three representative heme-containing proteins were studied, with an emphasis on results obtained under neutral (pH 7) aqueous conditions. The noncovalently bound heme in myoglobin and hemoglobin may be readily distinguished from the covalently bound heme prosthetic group attached to cytochrome c by using collisioninduced dissociation in the free-jet expansion region of the mass spectrometer as well as in the collision quadrupole with premass selection. The charge state of iron in the expelled heme from myoglobin and hemoglobin appears to be 3+ but 2f for heme expelled from cytochrome c. PMID- 24227667 TI - Stepwise refolding of Acid-denatured myoglobin: Evidence from electrospray mass spectrometry. AB - Application of electrospray mass spectrometry (ES/MS) to a protein refolding study was demonstrated. Acid denaturation of equine myoglobin was reversed by adding various amounts of ammonium hydroxide to the protein that was unfolded in 10% acetic acid. The protein refolding process was followed by ES/MS, in which both the changes in the protein charge-state distribution and mass were monitored. The ES/MS results show that the pH-dependent renaturation of the acid denatured myoglobin is stepwise, consisting of two major steps. The unfolded polypeptide chain first refolds to establish a compact nativelike structure, without the assistance of the heme prosthetic group. The newly formed binding cavity then retains the heme group by noncovalent interactions. It is also shown that inclusion of a stabilizing buffer, such as ammonium acetate, in the protein solution is greatly beneficial to the ES/MS detection of intact noncovalent globin/heme complex. PMID- 24227668 TI - Probing the helical content of growth hormone-releasing factor analogs using electrospray ionization mass spectrometry. AB - A series of growth hormone-releasing factor analogs have been studied by both circular dichroism and electrospray ionization mass spectrometry (ESI/MS). The peptides are 32 residues long and are known to adopt a random-coil structure in aqueous solution but become increasingly helical as the proportion of organic solvent is increased. Deuterium exchange was observed as an increase in mass of the peptide, as measured by ESI/MS. Rates of exchange were measured and half lives calculated for analogs containing amino acid substitutions designed to promote or discourage helix formation. Exchange was slower in peptides that are helical (as shown by circular dichroism) than in randomly coiled peptides. Solution conditions that favor helix formation also produced slower exchange rates. These studies suggest that ESI/MS can provide date about the extent and stability of helix formation. PMID- 24227669 TI - High-energy collision-induced dissociation of multiply charged polypeptides produced by electrospray. AB - The recent commercial implementation of an electrospray source on a four-sector mass spectrometer has allowed the study of high-energy collisional activation of multiply charged cations. With this configuration, higher mass-to-charge ratios can be accommodated in both precursor ion selection and fragment ion detection. Good mass accuracy facilitates analysis of fragment ions and allows more reliable mechanistic correlation of these fragments. A convenient scheme was devised to permit the use of kilovolt potentials in both MS-I and MS-II, with precursors of varying charge states. Algorithms were devised to assign masses of different types of multiply charged fragment ions. Nine polypeptides were studied in the mass range 2000-5000 Da. Through this entire mass range, fragment ions were observed to be amply formed by cleavages in both the backbone and side chains, analogous to high-energy collisional activation of singly charged ions. This stands in sharp contrast to the patterns reported with low-energy, multiple collisions. Abundances of sequence ion series are influenced by the positions of basic residues. Analysis of charge distributions in fragment ions also indicates that the charges tend to be spread out across the peptides. PMID- 24227670 TI - Electrospray ionization mass spectrometry of phosphopeptides isolated by on-line immobilized metal-ion affinity chromatography. AB - Electrospray ionization mass spectrometry (ESI/MS) affords a rapid and sensitive technique for determining peptides produced by the enzymatic digestion of phosphoroteins. When coupled with on-line immobilized metal-ion affinity chromatography (IMAC), the combmation allows separation and mass spectrometric identification of phosphorylated and nonphosphorylated peptides. In this study, the feasibility and general applicability of on-line IMAC/ESI/MS is investigated by using immobilized ferric ions for selective chelation of several phosphotyrosine and phosphoserine peptides. The sensitivity and practicality of the technique for phosphoproteins are demonstrated via the analysis of 30 pmol (~0.7 MUg) of bovine beta-casein purified by sodium dodecylsulfate-polyacrylamide gel electrophoresis, electroblotted onto a polyvinylidene difluoride membrane, and digested in situ with trypsin. It is observed that on-line IMAC/ESI/MS suffers less from sample losses than experiments performed off-line, suggesting that the limiting factors in sensitivity for this technique are the purification procedures and sample handling rather than the IMAC and mass spectrometry. Thus, the ability to inject the tryptic digest of an electroblotted protein directly onto the column without buffer exchange and to analyze the eluent directly via on line coupling of the IMAC column to the mass spectrometer greatly reduces sample losses incurred through sample handling and provides a convenient method for analyzing phosphopeptides at low levels. PMID- 24227671 TI - Application of electrospray mass spectrometry and matrix-assisted laser desorption ionization time-of-flight mass spectrometry for molecular weight assignment of peptides in complex mixtures. AB - Electrospray mass spectrometry (ES/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF/MS) were used to provide mass spectra from seven elapid snake venoms. Spectral interpretation was much simpler for MALDI/TOF/MS. ES/MS proved more useful for the provision of molecular weight data for very closely related peptides, but suppression of higher molecular weight compounds was seen to occur during flow injection analysis. MALDI/TOF/MS proved useful for providing a complete picture of the venom, but the low resolution led to obscuring of major ions, and the mass accuracy was poorer for known peptides. Suppression also occurred during MALDI/TOF/MS but could be overcome using alternative matrices because the spectra were very dependent on the choice of matrix. ES/MS and MALDI/TOF/MS provide complementary and confirmatory information such that for the anal sis of complex peptide mixtures (snake venoms), the use of both techniques is desirable. PMID- 24227674 TI - MEDIPS: genome-wide differential coverage analysis of sequencing data derived from DNA enrichment experiments. AB - MOTIVATION: DNA enrichment followed by sequencing is a versatile tool in molecular biology, with a wide variety of applications including genome-wide analysis of epigenetic marks and mechanisms. A common requirement of these diverse applications is a comparison of read coverage between experimental conditions. The amount of samples generated for such comparisons ranges from few replicates to hundreds of samples per condition for epigenome-wide association studies. Consequently, there is an urgent need for software that allows for fast and simple processing and comparison of sequencing data derived from enriched DNA. RESULTS: Here, we present a major update of the R/Bioconductor package MEDIPS, which allows for an arbitrary number of replicates per group and integrates sophisticated statistical methods for the detection of differential coverage between experimental conditions. Our approach can be applied to a diversity of quantitative sequencing data. In addition, our update adds novel functionality to MEDIPS, including correlation analysis between samples, and takes advantage of Bioconductor's annotation databases to facilitate annotation of specific genomic regions. AVAILABILITY AND IMPLEMENTATION: The latest version of MEDIPS is available as version 1.12.0 and part of Bioconductor 2.13. The package comes with a manual containing detailed description of its functionality and is available at http://www.bioconductor.org. PMID- 24227675 TI - PhosphoNetworks: a database for human phosphorylation networks. AB - SUMMARY: Phosphorylation plays an important role in cellular signal transduction. Current phosphorylation-related databases often focus on the phosphorylation sites, which are mainly determined by mass spectrometry. Here, we present PhosphoNetworks, a phosphorylation database built on a high-resolution map of phosphorylation networks. This high-resolution map of phosphorylation networks provides not only the kinase-substrate relationships (KSRs), but also the specific phosphorylation sites on which the kinases act on the substrates. The database contains the most comprehensive dataset for KSRs, including the relationships from a recent high-throughput project for identification of KSRs using protein microarrays, as well as known KSRs curated from the literature. In addition, the database also includes several analytical tools for dissecting phosphorylation networks. PhosphoNetworks is expected to play a prominent role in proteomics and phosphorylation-related disease research. AVAILABILITY AND IMPLEMENTATION: http://www.phosphonetworks.org PMID- 24227676 TI - Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. AB - SUMMARY: Track data hubs provide an efficient mechanism for visualizing remotely hosted Internet-accessible collections of genome annotations. Hub datasets can be organized, configured and fully integrated into the University of California Santa Cruz (UCSC) Genome Browser and accessed through the familiar browser interface. For the first time, individuals can use the complete browser feature set to view custom datasets without the overhead of setting up and maintaining a mirror. AVAILABILITY AND IMPLEMENTATION: Source code for the BigWig, BigBed and Genome Browser software is freely available for non-commercial use at http://hgdownload.cse.ucsc.edu/admin/jksrc.zip, implemented in C and supported on Linux. Binaries for the BigWig and BigBed creation and parsing utilities may be downloaded at http://hgdownload.cse.ucsc.edu/admin/exe/. Binary Alignment/Map (BAM) and Variant Call Format (VCF)/tabix utilities are available from http://samtools.sourceforge.net/ and http://vcftools.sourceforge.net/. The UCSC Genome Browser is publicly accessible at http://genome.ucsc.edu. PMID- 24227677 TI - featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. AB - MOTIVATION: Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. RESULTS: We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. AVAILABILITY AND IMPLEMENTATION: featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages. PMID- 24227678 TI - CheNER: chemical named entity recognizer. AB - MOTIVATION: Chemical named entity recognition is used to automatically identify mentions to chemical compounds in text and is the basis for more elaborate information extraction. However, only a small number of applications are freely available to identify such mentions. Particularly challenging and useful is the identification of International Union of Pure and Applied Chemistry (IUPAC) chemical compounds, which due to the complex morphology of IUPAC names requires more advanced techniques than that of brand names. RESULTS: We present CheNER, a tool for automated identification of systematic IUPAC chemical mentions. We evaluated different systems using an established literature corpus to show that CheNER has a superior performance in identifying IUPAC names specifically, and that it makes better use of computational resources. AVAILABILITY AND IMPLEMENTATION: http://metres.udl.cat/index.php/9-download/4-chener, http://chener.bioinfo.cnio.es/ PMID- 24227679 TI - A mutation (L1014F) in the voltage-gated sodium channel of the grain aphid, Sitobion avenae, is associated with resistance to pyrethroid insecticides. AB - BACKGROUND: The grain aphid, Sitobion avenae Fabricius (Hemiptera: Aphididae), is an important pest of cereal crops. Pesticides are the main method for control but carry the risk of selecting for resistance. In response to reports of reduced efficacy of pyrethroid sprays applied to S. avenae, field samples were collected and screened for mutations in the voltage-gated sodium channel, the primary target site for pyrethroids. Aphid mobility and mortality to lambda-cyhalothrin were measured in coated glass vial bioassays. RESULTS: A single amino acid substitution (L1014F) was identified in the domain IIS6 segment of the sodium channel from the S. avenae samples exhibiting reduced pyrethroid efficacy. Bioassays on aphids heterozygous for the kdr mutation (SR) or homozygous for the wild-type allele (SS) showed that those carrying the mutation had significantly lower susceptibility to lambda-cyhalothrin. CONCLUSION: The L1014F (kdr) mutation, known to confer pyrethroid resistance in many insect pests, has been identified for the first time in S. avenae. Clonal lines heterozygous for the mutation showed 35-40-fold resistance to lambda-cyhalothrin in laboratory bioassays, consistent with the reported effect of this mutation on pyrethroid sensitivity in other aphid species. PMID- 24227680 TI - Age-related changes of hyoid bone position in healthy older adults with aspiration. AB - OBJECTIVES/HYPOTHESIS: Aspiration, the passage of a bolus below the vocal folds, increases morbidity and mortality in the elderly by increasing the risk of aspiration pneumonia and other conditions. We hypothesized that altered position of the hyoid bone associated with aging may negatively affect airway protection during swallowing (i.e., aspiration) in older adults. STUDY DESIGN: Retrospective study. METHODS: We re-reviewed computed tomography (CT) scans of the head from 40 older adults (65-80 years old), comprised of 20 aspirators and 20 nonaspirators, obtained from a previous cohort study. In addition, CT scans of the head from 40 young adults (20-40 years old) were retrieved from a medical records database. Three-dimensional reconstruction and 2-dimensional sagittal views were used to measure the distance between the mandible and hyoid bone. Comparisons between age groups, genders, and aspiration status were made. RESULTS: Older adults had a larger distance between the hyoid and mandible in both latitude and longitudinal positions compared to the young adults. Among older males, there was evidence that the hyoid bone in the aspirators tended to be positioned more posterior compared to the nonaspirators. CONCLUSIONS: The distance between the hyoid and mandible is increased with aging, and a more posterior position of the hyoid bone is correlated with aspiration in older males. These findings suggest that age related changes in hyoid bone position may be a component of decreased swallowing safety and aspiration in older adults and warrant further investigation. LEVEL OF EVIDENCE: N/A. PMID- 24227681 TI - Comparison of retinal and cerebral blood flow between continuous arterial spin labeling MRI and fluorescent microsphere techniques. AB - PURPOSE: To compare basal retinal and cerebral blood flow (BF) values using continuous arterial spin labeling (CASL) MRI and fluorescent microspheres. MATERIALS AND METHODS: A total of 41 animals were used. BF was measured using an established microsphere technique (a mixture of 2.5 million 8 MUm green and 0.5 million 10 MUm blue fluorescent microspheres) and CASL MRI blood flow measurement in the rat retina and brain at 7 Tesla (T) and 11.7T, respectively. RESULTS: Retinal BF by MRI was 1.18 +/- 0.57 mL/g/min and choroidal BF was 8.14 +/- 1.8 mL/g/min (n = 6). Microsphere retinal BF was 9.12 +/- 2.8 MUL/min per tissue and choroidal BF was 73.38 +/- 44 MUL/min per tissue (n = 18), corresponding to a retinal BF value of 1.22 +/- 0.36 mL/g/min by means of a wet weight conversion. The wet-weight of the choroid could not be determined. To corroborate our findings, cerebral BF (CBF) by MRI was also analyzed. In the cerebral cortices, CBF was 0.91 +/- 0.29 mL/g/min (n = 14) by CASL MRI and 1.09 +/- 0.37 mL/g/min (n = 6) by microspheres. There were no significant differences found between MRI and microsphere blood flow in the retina and brain. CONCLUSION: BF values in the rat retina and cerebral cortex by MRI are in agreement with those obtained by the microsphere technique. PMID- 24227683 TI - Site selection and pain outcome after autologous bone graft harvest. AB - BACKGROUND: In foot and ankle surgery, there are multiple sites used for autologous bone graft, including the proximal (PT) or distal tibia (DT), calcaneus (C), and iliac crest (ICBG). There has been no comparison between these anatomic areas and the potential for acute or persistent pain at 1 year. The purpose of this study was to prospectively compare patient-reported outcomes of acute and persistent pain at 1 year after surgery to determine if harvest site selection made a difference. METHODS: As part of a clinical trial examining ankle and hindfoot fusion rates with autograft compared with synthetic graft, the autologous bone graft harvest sites were assessed with visual analog pain outcome scores at 3, 24, 36, and 52 weeks after surgery. Patients with a score of 20+ defined clinically significant pain. Four harvest sites were compared: ICBG, PT, DT, and C. Fisher exact test was used to compare the graft site pain between locations. RESULTS: Twelve percent of subjects reported clinically significant pain at 24 weeks and 8.5% at 52 weeks postoperatively. Each lower extremity harvest site (C, DT, PT) showed higher rates of clinically significant graft harvest site pain than the ICBG at 52 weeks. CONCLUSIONS: Autologous bone graft harvest carried a risk of persistent pain at up to 1 year (weeks 24-52) in 18% of patients. Lower-extremity bone graft sites had the greatest risk for persistent pain at 1 year. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 24227682 TI - Enhancing tissue repair in annulus fibrosus defects of the intervertebral disc: analysis of a bio-integrative annulus implant in an in-vivo ovine model. AB - Annulus fibrosus repair techniques for the intervertebral disc (IVD) address the unsolved problem of reherniation after IVD herniation and might facilitate the development of nucleus pulposus replacement techniques for IVD diseases. This study investigates the suitability of a bio-integrative annulus implant.Standardized box defects were applied to the annulus L3/4 and L4/5 of 16 sheep, followed by randomized insertion of the textile polyglycolic acid/polyvinylidene fluoride annulus implant in one of the defects. Explantation was conducted after 2, 6 and 12 weeks, followed by provocative pressure testing and histological analysis. At 2 weeks' follow-up, all specimens of the control defect group demonstrated uncontained herniated nucleus pulposus tissue in the annulus defects. For the treated specimens, the annulus implant consistently provided an effective barrier for herniating nucleus pulposus tissue, with no implant dislocation at all time-points. After 2 weeks, a homogeneous cell infiltration of the annulus implant was observed, leading to a progressive directional matrix build-up. Repair tissue thickness was significantly stronger with the annulus implant at all follow-ups (p < 0.01). No pronounced foreign body reaction and no difference in the amount of supra-annular scar tissue over the defect sites were observed. The implantation procedure inflicted annulus damage adjacent to the defect. At later time-points, however, no difference in comparison with the control defect group was evident. The investigated biointegrative annulus implant showed promising results with regard to biointegration, enhancement of repair tissue and function as a mechanical barrier in an ovine model. PMID- 24227684 TI - An approach to mixed P(n)A(sm) ligand complexes. AB - The reaction of a P4 butterfly complex with yellow arsenic yields the largest mixed Pn Asm ligand complexes synthesized to date. [{Cp'''Fe(CO)2 }2 (MU,eta(1:1) -P4 )] reacts with As4 to yield [{Cp'''Fe}2 (MU,eta(4:4) -Pn As4-n )] and [Cp'''Fe(eta(5) -Pn As5-n )]. Mass spectrometry together with NMR spectroscopy and X-ray crystallography give clear evidence about the arrangement of the E positions within the cyclo-E5 and E4 moieties of the products. Moreover, the results of DFT calculations agree well with the experimental determined outcomes. By coordinating the E4 complex [{Cp'''Fe}2 (MU,eta(4:4) -Pn As4-n )] with CuCl, a rearrangement of the E positions occurs in favor with a preferred phosphorus coordination towards copper atoms in the resulting 1D polymeric chain. PMID- 24227685 TI - beta-cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome. AB - Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of beta-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient beta-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram beta-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in beta-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes. PMID- 24227687 TI - Comparison between high-resolution isotropic three-dimensional and high resolution conventional two-dimensional FSE MR images of the wrist at 3 tesla: a pilot study. AB - PURPOSE: To demonstrate the clinical feasibility of high-resolution three dimensional (3D) isotropic FSE MRI of the wrist by comparing it to high resolution conventional 2D FSE (2D) MRI. MATERIALS AND METHODS: Eleven healthy volunteers were enrolled. All images were obtained at 3 Tesla (T). Delineation of anatomic structures of the wrist, amount of artifact, quality of fat suppression, image blur, and overall quality were qualitatively evaluated. Relative signal intensity (SI) of each structure and relative signal contrast between structures of the wrist were quantitatively measured. RESULTS: The 2D MRI demonstrated significantly higher scores than 3D in anatomic delineation of the SL ligament (P = 0.013), fat suppression (P = 0.013), and image blur (P = 0.003). The remaining quantitative analyses, including overall quality, revealed no statistical significances between 2D and 3D MRI. There were no statistical differences in relative SI of each structure between 2D and 3D imaging, except for bone marrow with fat suppression. There were no significant differences in relative fluid to TFCC and fluid to bone marrow contrast between 2D and 3D imaging, suggesting that both sequences have similar rates of detection for TFCC pathology and bone marrow lesions. CONCLUSION: With regard to clinical applications, 3D MRI of the wrist has almost equal potential to 2D MRI. PMID- 24227686 TI - Inclusion of the orientational entropic effect and low-resolution experimental information for protein-protein docking in Critical Assessment of PRedicted Interactions (CAPRI). AB - Inclusion of entropy is important and challenging for protein-protein binding prediction. Here, we present a statistical mechanics-based approach to empirically consider the effect of orientational entropy. Specifically, we globally sample the possible binding orientations based on a simple shape complementarity scoring function using an FFT-type docking method. Then, for each generated orientation, we calculate the probability through the partition function of the ensemble of accessible states, which are assumed to be represented by the set of nearby binding modes. For each mode, the interaction energy is calculated using our ITScorePP scoring function that was developed in our laboratory based on principles of statistical mechanics. Using the above protocol, we present the results of our participation in Rounds 22-27 of the Critical Assessment of PRedicted Interactions (CAPRI) experiment for 10 targets (T46-T58). Additional experimental information, such as low-resolution small angle X-ray scattering data, was used when available. In the prediction (or docking) experiments of the 10 target complexes, we achieved correct binding modes for six targets: one with high accuracy (T47), two with medium accuracy (T48 and T57), and three with acceptable accuracy (T49, T50, and T58). In the scoring experiments of seven target complexes, we obtained correct binding modes for six targets: one with high accuracy (T47), two with medium accuracy (T49 and T50), and three with acceptable accuracy (T46, T51, and T53). PMID- 24227688 TI - Morphogenesis and three-dimensional movement of the stomach during the human embryonic period. AB - The stomach develops as the local widening of the foregut after Carnegie stage (CS) 13 that moves in a dramatic and dynamic manner during the embryonic period. Using the magnetic resonance images of 377 human embryos, we present the morphology, morphometry, and three-dimensional movement of the stomach during CS16 and CS23. The stomach morphology revealed stage-specific features. The angular incisura and the cardia were formed at CS18. The change in the angular incisura angle was approximately 90 degrees during CS19 and CS20, and was <90 degrees after CS 21. The prominent formations of the fundus and the pylorus differentiate at around CS20. Morphometry of the stomach revealed that the stomach gradually becomes "deflected" during development. The stomach may appear to move to the left laterally and caudally due to its deflection and differential growth. The track of the reference points in the stomach may reflect the visual three-dimensional movement. The movement of point M, representing the movement of the greater curvature, was different from that of points C (cardia) and P (pyloric antrum). The P and C were located just around the midsagittal plane in all the stages observed. Point M moved in the caudal-left lateral direction until CS22. Moreover, the vector CP does not rotate around the dorsoventral axis, as widely believed, but around the transverse axis. The plane CPM rotated mainly around the longitudinal axis. The data obtained will be useful for prenatal diagnosis in the near future. PMID- 24227689 TI - Chiral copper(II) phosphate catalyzed enantioselective synthesis of isochromene derivatives by sequential intramolecular cyclization and asymmetric transfer hydrogenation of o-alkynylacetophenones. PMID- 24227690 TI - Cardiovascular magnetization transfer ratio imaging compared with histology: a postmortem study. AB - Cardiovascular magnetization transfer ratio (MTR) imaging by steady state free precession is a promising imaging method to assess microstructural changes within the myocardium. Hence, MTR imaging was correlated to histological analysis. Three postmortem cases were selected based on a suspicion of myocardial infarction. MTR and T2 -weighted (T2w ) imaging was performed, followed by autopsy and histological analysis. All tissue abnormalities, identified by autopsy or histology, were retrospectively selected on visually matched MTR and T2w images, and corresponding MTR values compared with normal appearing tissue. Regions of elevated MTR (up to approximately 20%, as compared to normal tissue), appearing hypo-intense in T2w -images, revealed the presence of fibrous tissue in microscopic histological analysis. Macroscopic observation (autopsy) described scar tissue only in one case. Regions of reduced MTR (up to approximately 20%) corresponded either to (i) the presence of edema, appearing hyperintense in T2w images and confirmed by autopsy, or to (ii) inflammatory granulocyte infiltration at a microscopic level, appearing as hypo-intense T2w -signal, but not observed by autopsy. Findings from cardiovascular MTR imaging corresponded to histology results. In contrast to T2w -imaging, MTR imaging discriminated between normal myocardium, scar tissue and regions of acute myocardial infarction in all three cases. PMID- 24227691 TI - 25th anniversary article: Designer hydrogels for cell cultures: a materials selection guide. AB - Cell culturing, whether for tissue engineering or cell biology studies, always involves placing cells in a non-natural environment and no material currently exist that can mimic the entire complexity of natural tissues and variety of cell matrix interactions that is found in vivo. Here, we review the vast range of hydrogels, composed of natural or synthetic polymers that provide a route to tailored microenvironments. PMID- 24227692 TI - Intrinsic rewards, fruit and vegetable consumption, and habit strength: a three wave study testing the associative-cybernetic model. AB - BACKGROUND: Habit formation is thought to lead to long-term maintenance of fruit and vegetable consumption. Habits develop through context-dependent repetition, but additional variables such as intrinsic reward of behaviour may influence habit strength. Drawing upon the Associative-Cybernetic Model, this exploratory study tested different pathways by which intrinsic reward may influence fruit and vegetable consumption habit strength. METHODS: In a three-wave study of fruit and vegetable intake in adults (N = 127) from the general population, intrinsic reward, intention, and self-efficacy were assessed at baseline, fruit and vegetable consumption and intrinsic reward two weeks later, and habit strength another two weeks later. Direct, indirect, and moderation effects of intrinsic reward on habit strength were tested simultaneously in a moderated mediation model. RESULTS: Intrinsic reward had a positive indirect effect on habit strength through its influence on the frequency of fruit and vegetable consumption. Further, the relationship between fruit and vegetable consumption and habit was stronger where consumption was considered more intrinsically rewarding. CONCLUSIONS: Findings highlight the potential relevance of intrinsic reward to habit. We suggest that intrinsic rewards from behaviour may not only facilitate habit via behaviour frequency, but also reinforce the relationship between behavioural repetition and habit strength. PMID- 24227694 TI - Defective bone microstructure in hydronephrotic mice: a histomorphometric study in ICR/Mlac-hydro mice. AB - Chronic renal impairment can lead to bone deterioration and abnormal bone morphology, but whether hydronephrosis is associated with bone loss remains unclear. Herein, we aimed to use computer-assisted bone histomorphometric technique to investigate microstructural bone changes in Imprinting Control Region (ICR) mice with a spontaneous mutation that was associated with bilateral nonobstructive hydronephrosis (ICR/Mlac-hydro). The results showed that 8-week old ICR/Mlac-hydro mice manifested decreases in trabecular bone number and thickness, and an increased trabecular separation, thereby leading to a reduction in trabecular bone volume compared with the wild-type mice. Furthermore, histomorphometric parameters related to both bone resorption and formation, that is, eroded surface, osteoclast surface, and osteoblast surface, were much lower in ICR/Mlac-hydro mice than in the wild type. A decrease in moment of inertia was found in ICR/Mlac-hydro mice, indicating a decrease in bone strength. In conclusion, ICR/Mlac-hydro mice exhibited trabecular bone loss, presumably caused by marked decreases in both osteoblast and osteoclast activities, which together reflected abnormally low bone turnover. Thus, this mouse strain appeared to be a valuable model for studying the hydronephrosis-associated bone disease. PMID- 24227693 TI - A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure. AB - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis. METHODS: Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones. RESULTS: Granulocyte PNH clones >= 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher sensitivity analyses detected PNH clones >= 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones >= 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) >= 1.5 * upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%). CONCLUSIONS: These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care. PMID- 24227695 TI - An unconventional glycosyl transfer reaction: glucansucrase GTFA functions as an allosyltransferase enzyme. PMID- 24227696 TI - Imaging of the murine biliopancreatic tract at 7 Tesla: technique and results in a model of primary sclerosing cholangitis. AB - PURPOSE: To assess the feasibility of a 7 Tesla (T) MR cholangiopancreatography (MRCP) protocol to image the morphology and detect and intraindividually monitor pathological changes of the biliopancreatic tract in a mouse model of primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: Six female Mdr2(Abcb)(-/-) mice, a well-established model of PSC, were imaged five times during weeks 10-19. Three wild-type controls were imaged at age 15 weeks. MRCP acquisition with three dimensional fast recovery fast spin echo sequences (3D-FRFSE) was performed using three sequences with different resolutions, repetition times (TR), and with/without respiration-gating in a 7 T preclinical MRI system. Image quality and visualization of five biliopancreatic structures were evaluated by three independent readers. RESULTS: Image quality was rated diagnostically sufficient in 86% of the datasets acquired without gating and in 100% for the respiration gated sequences. Intrahepatic ducts were well visualized (>= 97%) in Mdr2(-/-) mice. Stenoses and dilatations of the biliary ducts were intraindividually monitored. Progression and regression of bile duct pathologies were sufficiently assessed during the observation time. CONCLUSION: High-quality respiration-gated MRCP of the Mdr2(-/-) PSC model at 7 T allows for in vivo imaging of murine biliopancreatic tract and monitoring of bile duct pathologies, permitting longitudinal intraindividual studies in murine models of inflammatory bile duct diseases. PMID- 24227697 TI - Algal biomass conversion to bioethanol - a step-by-step assessment. AB - The continuous growth in global population and the ongoing development of countries such as China and India have contributed to a rapid increase in worldwide energy demand. Fossil fuels such as oil and gas are finite resources, and their current rate of consumption cannot be sustained. This, coupled with fossil fuels' role as pollutants and their contribution to global warming, has led to increased interest in alternative sources of energy production. Bioethanol, presently produced from energy crops, is one such promising alternative future energy source and much research is underway in optimizing its production. The economic and temporal constraints that crop feedstocks pose are the main downfalls in terms of the commercial viability of bioethanol production. As an alternative to crop feedstocks, significant research efforts have been put into utilizing algal biomass as a feedstock for bioethanol production. Whilst the overall process can vary, the conversion of biomass to bioethanol usually contains the following steps: (i) pretreatment of feedstock; (ii) hydrolysis; and (iii) fermentation of bioethanol. This paper reviews different technologies utilized in the pretreatment and fermentation steps, and critically assesses their applicability to bioethanol production from algal biomass. Two different established fermentation routes, single-stage fermentation and two-stage gasification/fermentation processes, are discussed. The viability of algal biomass as an alternative feedstock has been assessed adequately, and further research optimisation must be guided toward the development of cost-effective scalable methods to produce high bioethanol yield under optimum economy. PMID- 24227698 TI - A bioinspired soft actuated material. AB - A class of soft actuated materials that can achieve lifelike motion is presented. By embedding pneumatic actuators in a soft material inspired by a biological muscle fibril architecture, and developing a simple finite element simulation of the same, tunable biomimetic motion can be achieved with fully soft structures, exemplified here by an active left ventricle simulator. PMID- 24227699 TI - Targeted next-generation sequencing using fine-needle aspirates from adenocarcinomas of the lung. AB - BACKGROUND: Molecular testing of cancer is increasingly critical to medicine. Next-generation sequencing (NGS) provides comprehensive, unbiased, and inexpensive mutation analysis of multiple genes with a single test. However, to the authors' knowledge, the usefulness of NGS in fine-needle aspiration (FNA) specimens, which may be the only specimens available, is unknown. Non-small cell lung cancer (NSCLC) is an ideal model in which to evaluate cytopathologic applications of NGS because FNA is used for diagnosis and staging and specific molecular therapeutic targets in NSCLC are known. Herein, the performance and quality of targeted NGS in FNA specimens from a small series of lung adenocarcinomas is evaluated. METHODS: Sequence data were generated from FNA specimens and paired formalin-fixed paraffin-embedded (FFPE) tissues from 5 patients with lung adenocarcinoma. DNA was isolated from FNA aspirate smears and cores of FFPE tissue. Multiplex sequencing of 27 cancer-related genes was performed after hybrid capture enrichment. Read-quality metrics and single nucleotide variant calls were compared. RESULTS: The overall concordance of total reads across specimens was > 99% and the average concordance of single-nucleotide variants was 99.5%. The total reads generated, as well as the percentages of mapped, on-target, and unique reads were statistically indistinguishable (P > 0.05) between FFPE and FNA preparations. There also was no difference in the depth of sequencing coverage, including exon-level coverage in known lung cancer mutation hotspots. CONCLUSIONS: DNA isolated from FNA slides yields comprehensive, accurate, and statistically indistinguishable sequence information compared with that obtained from FFPE tissue. These results support the integration of NGS technologies into the standard cytopathology workflow. Cancer (Cancer Cytopathol) 2014;122:104-13. (c) 2013 American Cancer Society. PMID- 24227700 TI - Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals. AB - BACKGROUND: Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined. OBJECTIVE: To investigate patterns and predictors of opioid utilization in nonsurgical admissions to US hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events. DESIGN, SETTING, AND PATIENTS: Adult nonsurgical admissions to 286 US hospitals. MEASUREMENTS: Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. RESULTS: Of 1.14 million admissions, opioids were used in 51%. The mean +/- standard deviation daily dose received in oral morphine equivalents was 68 +/- 185 mg; 23% of exposed received a total daily dose of >=100 mg oral morphine equivalents. Opioid-prescribing rates ranged from 5% in the lowest-prescribing hospital to 72% in the highest-prescribing hospital (mean, 51% +/- 10%). After adjusting for patient characteristics, the adjusted opioid-prescribing rates ranged from 33% to 64% (mean, 50% +/- standard deviation 4%). Among exposed, 0.60% experienced severe opioid-related adverse events. Hospitals with higher opioid-prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (relative risk: 1.23 [1.14-1.33] for highest-prescribing compared with lowest prescribing quartile). CONCLUSIONS: The majority of hospitalized nonsurgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated. PMID- 24227701 TI - Prevalence and severity of categorical and dimensional personality disorders in adolescents with eating disorders. AB - OBJECTIVE: The objective of this study is to explore and compare the prevalence of categorical and dimensional personality disorders (PDs) and their severity in Spanish adolescents with Eating Disorders (EDs). METHOD: Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and International Classification of Diseases, Tenth Revision-10 modules of the International Personality Disorder Examination were administered to a sample of 100 female adolescents with EDs (mean age=15.8 years, SD=0.9). RESULTS: 'Thirty-three per cent of the sample had at least one PD, in most cases a simple PD. The rate of PDs was 64-76% in bulimia patients, 22-28% in anorexia and 25% in EDs not otherwise specified. The highest dimensional scores were observed in bulimia, [corrected] mainly in borderline and histrionic PDs, and higher scores for anankastic PD in anorexia than in the other ED diagnoses. Overall, purging type EDs had higher cluster B personality pathology scores than restrictive type.' [corrected] The Publisher would like to apologize for this error and any confusion it may have caused. [corrected]. DISCUSSION: Adolescent female patients with ED have a risk of presenting a comorbid PD, especially patients with bulimia and purging type EDs. PMID- 24227702 TI - Mechanistic insights from substrate preference in unsaturated glucuronyl hydrolase. AB - Natural and synthetic unsaturated glucuronides were tested as substrates for Clostridium perfringens unsaturated glucuronyl hydrolase to probe its mechanism and to guide inhibitor design. Of the natural substrates, a chondroitin disaccharide substrate with sulfation of the primary alcohol on carbon 6 of its N acetylgalactosamine moiety was found to have the highest turnover number of any substrate reported for an unsaturated glucuronyl hydrolase, with kcat =112 s(-1) . Synthetic aryl glycoside substrates with electron-withdrawing aglycone substituents were cleaved more slowly than those with electron-donating substituents. Similarly, an unsaturated glucuronyl fluoride was found to be a particularly poor substrate, with kcat /Km =44 nM(-1) s(-1) -a very unusual result for a glycoside-cleaving enzyme. These results are consistent with a transition state with positive charge at carbon 5 and the endocyclic oxygen, as anticipated in the hydration mechanism proposed. However, several analogues designed to take advantage of strong enzyme binding to such a transition state showed little to no inhibition. This result suggests that further work is required to understand the true nature of the transition state stabilised by this enzyme. PMID- 24227703 TI - Variable spatiotemporal resolution three-dimensional Dixon sequence for rapid dynamic contrast-enhanced breast MRI. AB - PURPOSE: To investigate a new variable spatiotemporal resolution dynamic contrast enhanced (DCE) MRI method termed DIfferential Subsampling with Cartesian Ordering (DISCO), for imaging of breast cancer. MATERIALS AND METHODS: DISCO combines variable density, pseudorandom k-space segmentation and two-point Dixon fat-water separation for high spatiotemporal resolution breast DCE MRI. During the contrast wash-in phase, view sharing is used to achieve high temporal resolution. Forty patients referred for breast MRI were imaged, 26 using the proposed DISCO sequence and 14 using a conventional low-spatial-resolution dynamic sequence (VIBRANT-FLEX) on a 3 Tesla scanner. DISCO dynamic images from 14 patients were compared with VIBRANT-FLEX images from 14 other patients. The image quality assessed by radiologist image ranking in a blinded manner, and the temporal characteristics of the two sequences were compared. RESULTS: A spatial resolution of 1.1 * 1.1 * 1.2 mm(3) (160 slices, 28 cm field of view) was achieved with axial bilateral coverage in 120 s. Dynamic images with ~ 9 s effective temporal resolution were generated during the 2-min contrast wash-in phase. The image quality of DISCO dynamic images ranked significantly higher than low spatial resolution VIBRANT-FLEX images (19.5 versus 9.5, Mann-Whitney U-test P = 0.00914), with no significant differences in the maximum slope of aortic enhancement. CONCLUSION: DISCO is a promising variable-spatiotemporal-resolution imaging sequence for capturing the dynamics of rapidly enhancing tumors as well as structural features postcontrast. A near 1-mm isotropic spatial resolution was achieved with postcontrast static phase images in 120 s and dynamic phase images acquired in 9 s per phase. PMID- 24227704 TI - From flavors and pharmaceuticals to advanced biofuels: production of isoprenoids in Saccharomyces cerevisiae. AB - Isoprenoids denote the largest group of chemicals in the plant kingdom and are employed for a wide range of applications in the food and pharmaceutical industry. In recent years, isoprenoids have additionally been recognized as suitable replacements for petroleum-derived fuels and could thus promote the transition towards a more sustainable society. To realize the biofuel potential of isoprenoids, a very efficient production system is required. While complex chemical structures as well as the low abundance in nature demonstrate the shortcomings of chemical synthesis and plant extraction, isoprenoids can be produced by genetically engineered microorganisms from renewable carbon sources. In this article, we summarize the development of isoprenoid applications from flavors and pharmaceuticals to advanced biofuels and review the strategies to design microbial cell factories, focusing on Saccharomyces cerevisiae for the production of these compounds. While the high complexity of biosynthetic pathways and the toxicity of certain isoprenoids still denote challenges that need to be addressed, metabolic engineering has enabled large-scale production of several terpenoids and thus, the utilization of these compounds is likely to expand in the future. PMID- 24227705 TI - Synthesis of asymmetrically substituted terpyridines by palladium-catalyzed direct C-H arylation of pyridine N-oxides. AB - The synthesis of asymmetrically substituted 2,2':6',2''-terpyridines is reported. First, palladium-catalyzed C-H arylation of pyridine N-oxides with substituted bromopyridines gave 2,2'-bipyridine N-oxides, which were further arylated in a second step to form 2,2':6',2''-terpyridine N-oxides. Yields of up to 77% were obtained with N-oxides bearing an electron-withdrawing ethoxycarbonyl substituent in the 4-position. Pd(OAc)2 with either P(tBu)3 or P(o-tolyl)3 was used as the catalyst. Cyclometalated complexes derived from Pd(OAc)2 and these phosphines were also effective. K3PO4 as the base gave better results than K2CO3. Subsequent deoxygenation with H2 and Pd/C as the catalyst gave the asymmetrically substituted 2,2':6',2''-terpyridines in near quantitative yield. This reaction sequence significantly reduces the number of steps required in comparison with known cross-coupling methods and therefore allows convenient and scalable access to substituted terpyridines. PMID- 24227706 TI - Dedifferentiated liposarcoma and pleomorphic liposarcoma: a comparative study of cytomorphology and MDM2/CDK4 expression on fine-needle aspiration. AB - BACKGROUND: Dedifferentiated liposarcoma (DDLPS) and pleomorphic liposarcoma (PLPS) are distinct high-grade liposarcomas. DDLPS is a nonlipogenic sarcoma characterized by amplification of MDM2 and CDK4. PLPS is a high-grade sarcoma containing lipoblasts, characterized by a complex karyotype and a more aggressive clinical course. Rarely, DDLPS shows lipogenic differentiation, mimicking PLPS. The cytomorphologic features of DDLPS and PLPS and the utility of ancillary studies have not been systemically analyzed. METHODS: Cytologic preparations of 25 DDLPS and 13 PLPS, all histologically confirmed, were retrospectively reviewed along with clinical and cytogenetic data. Sample cellularity, vascular architecture, background material, predominant cell morphology, quality of the cytoplasm, and nuclear pleomorphism were compared for both tumor types. Immunohistochemistry for MDM2 and CDK4 was performed on cell blocks and/or core needle biopsies. RESULTS: Fine-needle aspirate smears from both DDLPS and PLPS were variably cellular, composed of cellular clusters and noncohesive cells. Abundant myxoid stroma was present in ~25% of DDLPS and PLPS cases, whereas branching curvilinear vessels were more common in DDLPS than in PLPS (7 of 25 versus 2 of 13). Tumors were composed of predominantly spindled (18 of 25 DDLPS versus 3 of 13 PLPS) or epithelioid cells (7 of 25 DDLPS versus 6 of 13 PLPS). Pleomorphic cells were predominant in 3 PLPS, and were frequent in both (13 of 25 DDLPS versus 10 of 13 PLPS). The cytoplasm was mostly fibrillary and often vacuolated in both entities. Other features included necrosis, mitoses, and a prominent inflammatory infiltrate. The main cytologic differences were the presence of marked pleomorphism, abundant lipoblasts, and cells with microvacuolated cytoplasm in most PLPS. A total of 24 (96%) and 20 (80%) cases of DDLPS expressed MDM2 and CDK4, respectively, whereas none of the PLPS expressed both markers. Six DDLPS tested showed ring or giant marker chromosomes and/or MDM2 amplification by fluorescence in situ hybridization; 2 PLPS had complex karyotypes. CONCLUSIONS: DDLPS and PLPS exhibit variable and occasionally overlapping cytologic features. The presence of lipoblasts, cells with microvacuolated cytoplasm, and marked pleomorphism are more suggestive of PLPS, but these characteristics can be present in DDLPS. Coexpression of MDM2 and CDK4 distinguishes DDLPS from PLPS. PMID- 24227707 TI - The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission. AB - BACKGROUND: Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. OBJECTIVE: To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. DESIGN: Retrospective and prospective cohort. SETTING: Healthcare system consisting of 3 hospitals. PATIENTS: All adult patients admitted from August 2009 to September 2012. INTERVENTIONS: An automated readmission risk flag integrated into the EHR. MEASURES: Thirty-day all-cause and 7-day unplanned healthcare system readmissions. RESULTS: Using retrospective data, a single risk factor, >= 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30 day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. CONCLUSIONS: An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. PMID- 24227708 TI - The protein kinase A regulatory subunit R1A (Prkar1a) plays critical roles in peripheral nerve development. AB - Signaling through cAMP has been implicated in Schwann cell (SC) proliferation and myelination, but the signaling pathway components downstream of cAMP required for SC function remain unknown. Protein kinase A (PKA) is a potential downstream effector of cAMP. Here, we induced loss of Prkar1a, the gene encoding the type 1A regulatory subunit of PKA, in SC to study its role in nerve development; loss of Prkar1a is predicted to elevate PKA activity. Conditional Prkar1a knock-out in mouse SC (Prkar1a-SCKO) resulted in a dramatic and persistent axonal sorting defect, and unexpectedly decreased SC proliferation in Prkar1a-SCKO nerves in vivo. Effects were cell autonomous as they were recapitulated in vitro in Prkar1a SCKO SC, which showed elevated PKA activity. In the few SCs sorted into 1:1 relationships with axons in vivo, SC myelination was premature in Prkar1a-SCKO nerves, correlating with global increase in the cAMP-regulated transcription factor Oct-6 and expression of myelin basic protein. These data reveal a previously unknown role of PKA in axon sorting, an unexpected inhibitory role of PKA on SC cell proliferation in vivo and define the importance of Prkar1a in peripheral nerve development. PMID- 24227709 TI - Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation. AB - The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of the vertebrate nervous system. We previously showed that the adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential for peripheral nervous system myelination, although the molecular mechanisms by which Gpr126 functions were incompletely understood. aGPCRs are a significantly understudied protein class, and it was unknown whether Gpr126 couples to G-proteins. Here, we analyze Dhh(Cre);Gpr126(fl/fl) conditional mutants, and show that Gpr126 functions in Schwann cells (SCs) for radial sorting of axons and myelination. Furthermore, we demonstrate that elevation of cAMP levels or protein kinase A activation suppresses myelin defects in Gpr126 mouse mutants and that cAMP levels are reduced in conditional Gpr126 mutant peripheral nerve. Finally, we show that GPR126 directly increases cAMP by coupling to heterotrimeric G-proteins. Together, these data support a model in which Gpr126 functions in SCs for proper development and myelination and provide evidence that these functions are mediated via G-protein-signaling pathways. PMID- 24227710 TI - Safety signals in the primate amygdala. AB - The ability to distinguish danger from safety is crucial for survival. On the other hand, anxiety disorders can result from failures to dissociate safe cues from those that predict dangerous outcomes. The amygdala plays a major role in learning and signaling danger, and recently, evidence accumulates that it also acquires information to signal safety. Traditionally, safety is explored by paradigms that change the value of a previously dangerous cue, such as extinction or reversal; or by paradigms showing that a safe cue can inhibit responses to another danger-predicting cue, as in conditioned-inhibition. In real-life scenarios, many cues are never paired or tested with danger and remain neutral all along. A detailed study of neural responses to unpaired conditioned-stimulus (CS-) can therefore indicate whether information on safety-by-comparison is also acquired in the amygdala. We designed a multiple-CS study, with CS- from both visual and auditory modalities. Using discriminative aversive-conditioning, we find that responses in the primate amygdala develop for CS- of the same modality and of a different modality from that of the aversive CS+. Moreover, we find that responses are comparable in proportion, sign (increase/decrease), onset, and magnitude. These results indicate that the primate amygdala actively acquires signals about safety, and strengthen the hypothesis that failure in amygdala processing can result in failure to distinguish dangerous cues from safe ones and lead to maladaptive behaviors. PMID- 24227711 TI - alpha6beta1 and alpha7beta1 integrins are required in Schwann cells to sort axons. AB - During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination and is arrested in human neuropathies because of laminin deficiency. Experiments in mice using targeted mutagenesis have confirmed that laminins 211, 411, and receptors containing the beta1 integrin subunit are required for radial sorting; however, which of the 11 alpha integrins that can pair with beta1 forms the functional receptor is unknown. Here we conditionally deleted all the alpha subunits that form predominant laminin binding beta1 integrins in Schwann cells and show that only alpha6beta1 and alpha7beta1 integrins are required and that alpha7beta1 compensates for the absence of alpha6beta1 during development. The absence of either alpha7beta1 or alpha6beta1 integrin impairs the ability of Schwann cells to spread and to bind laminin 211 or 411, potentially explaining the failure to extend cytoplasmic processes around axons to sort them. However, double alpha6/alpha7 integrin mutants show only a subset of the abnormalities found in mutants lacking all beta1 integrins, and a milder phenotype. Double-mutant Schwann cells can properly activate all the major signaling pathways associated with radial sorting and show normal Schwann cell proliferation and survival. Thus, alpha6beta1 and alpha7beta1 are the laminin-binding integrins required for axonal sorting, but other Schwann cell beta1 integrins, possibly those that do not bind laminins, may also contribute to radial sorting during peripheral nerve development. PMID- 24227712 TI - Changes in brain function occur years before the onset of cognitive impairment. AB - To develop targeted intervention strategies for the treatment of Alzheimer's disease, we first need to identify early markers of brain changes that occur before the onset of cognitive impairment. Here, we examine changes in resting state brain function in humans from the Baltimore Longitudinal Study of Aging. We compared longitudinal changes in regional cerebral blood flow (rCBF), assessed by (15)O-water PET, over a mean 7 year period between participants who eventually developed cognitive impairment (n = 22) and those who remained cognitively normal (n = 99). Annual PET assessments began an average of 11 years before the onset of cognitive impairment in the subsequently impaired group, so all participants were cognitively normal during the scanning interval. A voxel-based mixed model analysis was used to compare groups with and without subsequent impairment. Participants with subsequent impairment showed significantly greater longitudinal rCBF increases in orbitofrontal, medial frontal, and anterior cingulate regions, and greater longitudinal decreases in parietal, temporal, and thalamic regions compared with those who maintained cognitive health. These changes were linear in nature and were not influenced by longitudinal changes in regional tissue volume. Although all participants were cognitively normal during the scanning interval, most of the accelerated rCBF changes seen in the subsequently impaired group occurred within regions thought to be critical for the maintenance of cognitive function. These changes also occurred within regions that show early accumulation of pathology in Alzheimer's disease, suggesting that there may be a connection between early pathologic change and early changes in brain function. PMID- 24227713 TI - A novel Hap1-Tsc1 interaction regulates neuronal mTORC1 signaling and morphogenesis in the brain. AB - Tuberous sclerosis complex (TSC) is a leading genetic cause of autism. The TSC proteins Tsc1 and Tsc2 control the mTORC1 signaling pathway in diverse cells, but how the mTORC1 pathway is specifically regulated in neurons remains to be elucidated. Here, using an interaction proteomics approach in neural cells including neurons, we uncover the brain-enriched protein huntingtin-associated protein 1 (Hap1) as a novel functional partner of Tsc1. Knockdown of Hap1 promotes specification of supernumerary axons in primary hippocampal neurons and profoundly impairs the positioning of pyramidal neurons in the mouse hippocampus in vivo. The Hap1 knockdown-induced phenotypes in primary neurons and in vivo recapitulate the phenotypes induced by Tsc1 knockdown. We also find that Hap1 knockdown in hippocampal neurons induces the downregulation of Tsc1 and stimulates the activity of mTORC1, as reflected by phosphorylation of the ribosomal protein S6. Inhibition of mTORC1 activity suppresses the Hap1 knockdown induced polarity phenotype in hippocampal neurons. Collectively, these findings define a novel link between Hap1 and Tsc1 that regulates neuronal mTORC1 signaling and neuronal morphogenesis, with implications for our understanding of developmental disorders of cognition. PMID- 24227714 TI - Medial habenula output circuit mediated by alpha5 nicotinic receptor-expressing GABAergic neurons in the interpeduncular nucleus. AB - The Chrna5 gene encodes the alpha5 nicotinic acetylcholine receptor subunit, an "accessory" subunit of pentameric nicotinic receptors, that has been shown to play a role in nicotine-related behaviors in rodents and is genetically linked to smoking behavior in humans. Here we have used a BAC transgenic mouse line, alpha5(GFP), to examine the cellular phenotype, connectivity, and function of alpha5-expressing neurons. Although the medial habenula (MHb) has been proposed as a site of alpha5 function, alpha5(GFP) is not detectable in the MHb, and alpha5 mRNA is expressed there only at very low levels. However, alpha5(GFP) is strongly expressed in a subset of neurons in the interpeduncular nucleus (IP), median raphe/paramedian raphe (MnR/PMnR), and dorsal tegmental area (DTg). Double label fluorescence in situ hybridization reveals that these neurons are exclusively GABAergic. Transgenic and conventional tract tracing show that alpha5(GFP) neurons in the IP project principally to the MnR/PMnR and DTg/interfascicular dorsal raphe, both areas rich in serotonergic neurons. The alpha5(GFP) neurons in the IP are located in a region that receives cholinergic fiber inputs from the ventral MHb, and optogenetically assisted circuit mapping demonstrates a monosynaptic connection between these cholinergic neurons and alpha5(GFP) IP neurons. Selective inhibitors of both alpha4beta2- and alpha3beta4 containing nicotinic receptors were able to reduce nicotine-evoked inward currents in alpha5(GFP) neurons in the IP, suggesting a mixed nicotinic receptor profile in these cells. Together, these findings show that the alpha5-GABAergic interneurons form a link from the MHb to serotonergic brain centers, which is likely to mediate some of the behavioral effects of nicotine. PMID- 24227715 TI - An updated midline rule: visual callosal connections anticipate shape and motion in ongoing activity across the hemispheres. AB - It is generally thought that callosal connections (CCs) in primary visual cortices serve to unify the visual scenery parted in two at the vertical midline (VM). Here, we present evidence that this applies also to visual features that do not cross yet but might cross the VM in the future. During reversible deactivation of the contralateral visual cortex in cats, we observed that ipsilaterally recorded neurons close to the border between areas 17 and 18 receive selective excitatory callosal input on both ongoing and evoked activity. In detail, neurons responding well to a vertical Gabor patch moving away from the deactivated hemifield decreased prestimulus and stimulus-driven activity much more than those preferring motion toward the cooled hemifield. Further, activity of neurons responding to horizontal lines decreased more than the response to vertical lines. Embedding a single Gabor into a collinear line context selectively stabilized responses, especially when the context was limited to the intact hemifield. These findings indicate that CCs interconnect not only neurons coding for similar orientations but also for similar directions of motion. We conclude that CCs anticipate stimulus features that are potentially relevant for both hemifields (i.e., coherent motion but also collinear shape) because already prestimulus activity and activity to stimuli not crossing the VM revealed feature specificity. Finally, we hypothesize that intrinsic and callosal networks processing different orientations and directions are anisotropic close to the VM facilitating perceptual grouping along likely future motion or (shape) trajectories before the visual stimulus arrives. PMID- 24227716 TI - Convergent rhythm generation from divergent cellular mechanisms. AB - Different modulatory inputs commonly elicit distinct rhythmic motor patterns from a central pattern generator (CPG), but they can instead elicit the same pattern. We are determining the rhythm-generating mechanisms in this latter situation, using the gastric mill (chewing) CPG in the crab (Cancer borealis) stomatogastric ganglion, where stimulating the projection neuron MCN1 (modulatory commissural neuron 1) or bath applying CabPK (C. borealis pyrokinin) peptide elicits the same gastric mill motor pattern, despite configuring different gastric mill circuits. In both cases, the core rhythm generator includes the same reciprocally inhibitory neurons LG (lateral gastric) and Int1 (interneuron 1), but the pyloric (food-filtering) circuit pacemaker neuron AB (anterior burster) is additionally necessary only for CabPK rhythm generation. MCN1 drives this rhythm generator by activating in the LG neuron the modulator-activated inward current (IMI), which waxes and wanes periodically due to phasic feedback inhibition of MCN1 transmitter release. Each buildup of IMI enables the LG neuron to generate a self terminating burst and thereby alternate with Int1 activity. Here we establish that CabPK drives gastric mill rhythm generation by activating in the LG neuron IMI plus a slowly activating transient, low-threshold inward current (ITrans-LTS) that is voltage, time, and Ca(2+) dependent. Unlike MCN1, CabPK maintains a steady IMI activation, causing a subthreshold depolarization in LG that facilitates a periodic postinhibitory rebound burst caused by the regular buildup and decay of the availability of ITrans-LTS. Thus, different modulatory inputs can use different rhythm-generating mechanisms to drive the same neuronal rhythm. Additionally, the same ionic current (IMI) can play different roles under these different conditions, while different currents (IMI, ITrans-LTS) can play the same role. PMID- 24227717 TI - CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells. AB - Juvenile neuronal ceroid lipofuscinosis (JNCL) is a fatal childhood-onset neurodegenerative disorder caused by mutations in ceroid lipofuscinosis neuronal 3 (CLN3), a hydrophobic transmembrane protein of unresolved function. Previous studies indicate blood-brain barrier (BBB) defects in JNCL, and our earlier report showed prominent Cln3 expression in mouse brain endothelium. Here we find that CLN3 is necessary for normal trafficking of the microdomain-associated proteins caveolin-1, syntaxin-6, and multidrug resistance protein 1 (MDR1) in brain endothelial cells. Correspondingly, CLN3-null cells have reduced caveolae, and impaired caveolae- and MDR1-related functions including endocytosis, drug efflux, and cell volume regulation. We also detected an abnormal blood-brain barrier response to osmotic stress in vivo. Evaluation of the plasma membrane with fluorescent sphingolipid probes suggests microdomain destabilization and enhanced fluidity in CLN3-null cells. In further work we found that application of the glycosphingolipid lactosylceramide to CLN3-deficient cells rescues protein transport and caveolar endocytosis. Last, we show that CLN3 localizes to the trans-Golgi network (TGN) and partitions with buoyant microdomain fractions. We propose that CLN3 facilitates TGN-to-plasma membrane transport of microdomain associated proteins. Insult to this pathway may underlie BBB dysfunction and contribute to JNCL pathogenesis. PMID- 24227718 TI - Cortical reorganization after long-term adaptation to retinal lesions in humans. AB - Single-unit recordings demonstrated that the adult mammalian visual cortex is capable of reorganizing after induced retinal lesions. In humans, whether the adult cortex is capable of reorganizing has only been studied using functional magnetic resonance imaging, with equivocal results. Here, we exploited the phenomenon of visual crowding, a major limitation on object recognition, to show that, in humans with long-standing retinal (macular) lesions that afflict the fovea and thus use their peripheral vision exclusively, the signature properties of crowding are distinctly different from those of the normal periphery. Crowding refers to the inability to recognize objects when the object spacing is smaller than the critical spacing. Critical spacing depends only on the retinal location of the object, scales linearly with its distance from the fovea, and is approximately two times larger in the radial than the tangential direction with respect to the fovea, thus demonstrating the signature radial-tangential anisotropy of the crowding zone. Using retinal imaging combined with behavioral measurements, we mapped out the crowding zone at the precise peripheral retinal locations adopted by individuals with macular lesions as the new visual reference loci. At these loci, the critical spacings are substantially smaller along the radial direction than expected based on the normal periphery, resulting in a lower scaling of critical spacing with the eccentricity of the peripheral locus and a loss in the signature radial-tangential anisotropy of the crowding zone. These results imply a fundamental difference in the substrate of cortical processing in object recognition following long-term adaptation to macular lesions. PMID- 24227719 TI - Preparing for selective inhibition within frontostriatal loops. AB - Action inhibition can globally prevent all motor output or selectively cancel specific actions during concurrent motor output. Here we examine the behavioral and neural basis of selective inhibition focusing on the role of preparation. In 18 healthy human participants we manipulated the extent to which they could prepare for selective inhibition by providing or withholding information on what actions might need to be stopped. We show that, on average, information improves both speed and selectivity of inhibition. Functional magnetic resonance imaging data show that preparation for selective inhibition engages the inferior frontal gyrus, supplementary motor area, and striatum. Examining interindividual differences, we find the benefit of proactive control to speed and selectivity of inhibition trade off against each other, such that an improvement in stopping speed leads to a deterioration of selectivity of inhibition, and vice versa. This trade-off is implemented through engagement of the dorsolateral prefrontal cortex and putamen. Our results suggest proactive selective inhibition is implemented within frontostriatal structures, and we provide evidence that a speed selectivity trade-off might underlie a range of findings reported previously. PMID- 24227720 TI - Tonic activation of Bax primes neural progenitors for rapid apoptosis through a mechanism preserved in medulloblastoma. AB - Commitment to survival or apoptosis within expanding progenitor populations poses distinct risks and benefits to the organism. We investigated whether specialized mechanisms regulate apoptosis in mouse neural progenitors and in the progenitor derived brain tumor medulloblastoma. Here, we identified constitutive activation of proapoptotic Bax, maintained in check by Bcl-xL, as a mechanism for rapid cell death, common to postnatal neural progenitors and medulloblastoma. We found that tonic activation of Bax in cerebellar progenitors, along with sensitivity to DNA damage, was linked to differentiation state. In cerebellar progenitors, active Bax localized to mitochondria, where it was bound to Bcl-xL. Disruption of Bax:Bcl-xL binding by BH3-mimetic ABT 737 caused rapid apoptosis of cerebellar progenitors and primary murine medulloblastoma cells. Conditional deletion of Mcl 1, in contrast, did not cause death of cerebellar progenitors. Our findings identify a mechanism for the sensitivity of brain progenitors to typical anticancer therapies and reveal that this mechanism persists in medulloblastoma, a malignant brain tumor markedly sensitive to radiation and chemotherapy. PMID- 24227721 TI - Longitudinal growth curves of brain function underlying inhibitory control through adolescence. AB - Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing continues to mature. PMID- 24227722 TI - D1 dopamine receptor coupling to PLCbeta regulates forward locomotion in mice. AB - Several studies have reported the coupling of dopamine signaling to phospholipase C beta (PLCbeta) both in vitro and in vivo. However, the precise physiological relevance of this signaling pathway in mediating dopamine behaviors is still unclear. Here we report that stimulation of dopamine receptor signaling in vivo with systemic administration of apomorphine, amphetamine, and cocaine leads to increased production of inositol triphosphate (IP3) in the mouse striatum. Using selective antagonists and dopamine D1 and D2 receptor knock-out animals, we show that the production of IP3 is mediated by the D1 receptor, but not the D2 receptor. A selective blocker of PLCbeta, U73122, was used to assess the physiological relevance of D1-mediated IP3 production. We show that U73122 inhibits the locomotor-stimulating effects of apomorphine, amphetamine, cocaine, and SKF81297. Furthermore, U73122 also suppresses the spontaneous hyperactivity exhibited by dopamine transporter knock-out mice. Importantly, the effects of U73122 are selective to dopamine-mediated hyperactivity, as this compound does not affect hyperactivity induced by the glutamate NMDA receptor antagonist MK801. Finally, we present evidence showing that an imbalance of D1- and D2-mediated signaling following U73122 treatment modifies the locomotor output of animals from horizontal locomotor activity to vertical activity, further highlighting the importance of the PLCbeta pathway in the regulation of forward locomotion via dopamine receptors. PMID- 24227723 TI - Frontal cortex activation causes rapid plasticity of auditory cortical processing. AB - Neurons in the primary auditory cortex (A1) can show rapid changes in receptive fields when animals are engaged in sound detection and discrimination tasks. The source of a signal to A1 that triggers these changes is suspected to be in frontal cortical areas. How or whether activity in frontal areas can influence activity and sensory processing in A1 and the detailed changes occurring in A1 on the level of single neurons and in neuronal populations remain uncertain. Using electrophysiological techniques in mice, we found that pairing orbitofrontal cortex (OFC) stimulation with sound stimuli caused rapid changes in the sound driven activity within A1 that are largely mediated by noncholinergic mechanisms. By integrating in vivo two-photon Ca(2+) imaging of A1 with OFC stimulation, we found that pairing OFC activity with sounds caused dynamic and selective changes in sensory responses of neural populations in A1. Further, analysis of changes in signal and noise correlation after OFC pairing revealed improvement in neural population-based discrimination performance within A1. This improvement was frequency specific and dependent on correlation changes. These OFC-induced influences on auditory responses resemble behavior-induced influences on auditory responses and demonstrate that OFC activity could underlie the coordination of rapid, dynamic changes in A1 to dynamic sensory environments. PMID- 24227724 TI - N-cadherin sustains motility and polarity of future cortical interneurons during tangential migration. AB - In the developing brain, cortical GABAergic interneurons migrate long distances from the medial ganglionic eminence (MGE) in which they are generated, to the cortex in which they settle. MGE cells express the cell adhesion molecule N cadherin, a homophilic cell-cell adhesion molecule that regulates numerous steps of brain development, from neuroepithelium morphogenesis to synapse formation. N cadherin is also expressed in embryonic territories crossed by MGE cells during their migration. In this study, we demonstrate that N-cadherin is a key player in the long-distance migration of future cortical interneurons. Using N-cadherin coated substrate, we show that N-cadherin-dependent adhesion promotes the migration of mouse MGE cells in vitro. Conversely, mouse MGE cells electroporated with a construct interfering with cadherin function show reduced cell motility, leading process instability, and impaired polarization associated with abnormal myosin IIB dynamics. In vivo, the capability of electroporated MGE cells to invade the developing cortical plate is altered. Using genetic ablation of N cadherin in mouse embryos, we show that N-cadherin-depleted MGEs are severely disorganized. MGE cells hardly exit the disorganized proliferative area. N cadherin ablation at the postmitotic stage, which does not affect MGE morphogenesis, alters MGE cell motility and directionality. The tangential migration to the cortex of N-cadherin ablated MGE cells is delayed, and their radial migration within the cortical plate is perturbed. Altogether, these results identify N-cadherin as a pivotal adhesion substrate that activates cell motility in future cortical interneurons and maintains cell polarity over their long-distance migration to the developing cortex. PMID- 24227725 TI - Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1 ADAM22 interaction and reduce synaptic AMPA receptors. AB - More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1 ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID- 24227727 TI - Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. AB - CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid beta, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid beta, in the aging brain. PMID- 24227726 TI - Tau pathology is present in vivo and develops in vitro in sensory neurons from human P301S tau transgenic mice: a system for screening drugs against tauopathies. AB - Intracellular tau aggregates are the neuropathological hallmark of several neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and cases of frontotemporal dementia, but the link between these aggregates and neurodegeneration remains unclear. Neuronal models recapitulating the main features of tau pathology are necessary to investigate the molecular mechanisms of tau malfunction, but current models show little and inconsistent spontaneous tau aggregation. We show that dorsal root ganglion (DRG) neurons in transgenic mice expressing human P301S tau (P301S-htau) develop tau pathology similar to that found in brain and spinal cord and a significant reduction in mechanosensation occurs before detectable fibrillar tau formation. DRG neuronal cultures established from adult P301S-htau mice at different ages retained the pattern of aberrant tau found in vivo. Moreover, htau became progressively hyperphosphorylated over 2 months in vitro beginning with nonsymptomatic neurons, while hyperphosphorylated P301S-htau-positive neurons from 5-month-old mice cultured for 2 months died preferentially. P301S-htau positive neurons grew aberrant axons, including spheroids, typically found in human tauopathies. Neurons cultured at advanced stages of tau pathology showed a 60% decrease in the fraction of moving mitochondria. SEG28019, a novel O GlcNAcase inhibitor, reduced steady-state pSer396/pSer404 phosphorylation over 7 weeks in a significant proportion of DRG neurons showing for the first time the possible beneficial effect of prolonged dosing of O-GlcNAcase inhibitor in vitro. Our system is unique in that fibrillar tau forms without external manipulation and provides an important new tool for understanding the mechanisms of tau dysfunction and for screening of compounds for treatment of tauopathies. PMID- 24227728 TI - Global facilitation of attended features is obligatory and restricts divided attention. AB - In many common situations such as driving an automobile it is advantageous to attend concurrently to events at different locations (e.g., the car in front, the pedestrian to the side). While spatial attention can be divided effectively between separate locations, studies investigating attention to nonspatial features have often reported a "global effect", whereby items having the attended feature may be preferentially processed throughout the entire visual field. These findings suggest that spatial and feature-based attention may at times act in direct opposition: spatially divided foci of attention cannot be truly independent if feature attention is spatially global and thereby affects all foci equally. In two experiments, human observers attended concurrently to one of two overlapping fields of dots of different colors presented in both the left and right visual fields. When the same color or two different colors were attended on the two sides, deviant targets were detected accurately, and visual-cortical potentials elicited by attended dots were enhanced. However, when the attended color on one side matched the ignored color on the opposite side, attentional modulation of cortical potentials was abolished. This loss of feature selectivity could be attributed to enhanced processing of unattended items that shared the color of the attended items in the opposite field. Thus, while it is possible to attend to two different colors at the same time, this ability is fundamentally constrained by spatially global feature enhancement in early visual-cortical areas, which is obligatory and persists even when it explicitly conflicts with task demands. PMID- 24227729 TI - Uncoupling of EphA/ephrinA signaling and spontaneous activity in neural circuit wiring. AB - Classic studies have proposed that genetically encoded programs and spontaneous activity play complementary but independent roles in the development of neural circuits. Recent evidence, however, suggests that these two mechanisms could interact extensively, with spontaneous activity affecting the expression and function of guidance molecules at early developmental stages. Here, using the developing chick spinal cord and the mouse visual system to ectopically express the inwardly rectifying potassium channel Kir2.1 in individual embryonic neurons, we demonstrate that cell-intrinsic blockade of spontaneous activity in vivo does not affect neuronal identity specification, axon pathfinding, or EphA/ephrinA signaling during the development of topographic maps. However, intrinsic spontaneous activity is critical for axon branching and pruning once axonal growth cones reach their correct topographic position in the target tissues. Our experiments argue for the dissociation of spontaneous activity from hard-wired developmental programs in early phases of neural circuit formation. PMID- 24227730 TI - The sigma-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor. AB - The sigma-1 receptor (Sig1R) is widely expressed in the CNS, where it has a neuroprotective role in ischemia and stroke and an involvement in schizophrenia. The Sig1R interacts functionally with a variety of ion channels, including the NMDA receptor (NMDAR). Here, we used atomic force microscopy (AFM) imaging to investigate the interaction between the Sig1R and the NMDAR. The Sig1R bound directly to GluN1/GluN2A NMDAR heterotetramers. Furthermore, the mean angle between pairs of bound Sig1Rs was 72 degrees . This result suggested that the Sig1R interacts with either GluN1 or GluN2A, but not both, and supports our recent demonstration that the NMDAR subunits adopt an adjacent (i.e., 1/1/2/2) arrangement. The Sig1R could be coisolated with GluN1 but not with GluN2A, indicating that GluN1 is its specific target within the NMDAR. Consistent with this conclusion, AFM imaging of coisolated Sig1R and GluN1 revealed GluN1 dimers decorated with Sig1Rs. In situ proximity ligation assays demonstrated that the Sig1R interacts with GluN1 (but not with GluN2A) within intact cells and also that its C terminus is extracellular. We conclude that the Sig1R binds to the GluN1/GluN2A NMDAR specifically via the GluN1 subunit. This interaction likely accounts for at least some of the modulatory effects of Sig1R ligands on the NMDAR. PMID- 24227731 TI - Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory. AB - In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ~3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time. PMID- 24227732 TI - The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses. AB - Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction in FXS. Matrix Metalloproteinase 9 (MMP-9) is an enzyme involved in activity-dependent reorganization of dendritic spine architecture and was shown to regulate spine morphology in a mouse model of FXS, the Fmr1 knock out mice. Here we show that MMP-9 mRNA is part of the FMRP complex and colocalizes in dendrites. In the absence of FMRP MMP-9 mRNA translation is increased at synapses, suggesting that this mechanism contributes to the increased metalloproteinase level at synapses of Fmr1 knock-out mice. We propose that such a local effect can contribute to the aberrant dendritic spine morphology observed in the Fmr1 knock-out mice and in patients with FXS. PMID- 24227733 TI - Early auditory processing in area V5/MT+ of the congenitally blind brain. AB - Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+. PMID- 24227734 TI - Body and object effectors: the organization of object representations in high level visual cortex reflects body-object interactions. AB - The principles driving the functional organization of object representations in high-level visual cortex are not yet fully understood. In four human fMRI experiments, we provide evidence that the organization of high-level visual cortex partly reflects the degree to which objects are typically controlled by the body to interact with the world, thereby extending the body's boundaries. Univariate whole-brain analysis showed an overlap between responses to body effectors (e.g., hands, feet, and limbs) and object effectors (e.g., hammers, combs, and tennis rackets) in lateral occipitotemporal cortex (LOTC) and parietal cortex. Region of interest analyses showed that a hand-selective region in left LOTC responded selectively to object effectors relative to a range of noneffector object control conditions (e.g., graspable objects, "act-on" objects, musical instruments). Object ratings showed that the strong response to object effectors in hand-selective LOTC was not due to general action-related object properties shared with these control conditions, such as hand priming, hand grasping, and hand-action centrality. Finally, whole-brain representational similarity analysis revealed that the similarity of multivoxel object response patterns in left lateral occipitotemporal cortex selectively predicted the degree to which objects were rated as being controlled by and extending the body. Together, these results reveal a clustering of body and object effector representations, indicating that the organization of object representations in high-level visual cortex partly reflects how objects relate to the body. PMID- 24227735 TI - Compression and suppression of shifting receptive field activity in frontal eye field neurons. AB - Before each saccade, neurons in frontal eye field anticipate the impending eye movement by showing sensitivity to stimuli appearing where the neuron's receptive field will be at the end of the saccade, referred to as the future field (FF) of the neuron. We explored the time course of this anticipatory activity in monkeys by briefly flashing stimuli in the FF at different times before saccades. Different neurons showed substantial variation in FF time course, but two salient observations emerged. First, when we compared the time span of stimulus probes before the saccade to the time span of FF activity, we found a striking temporal compression of FF activity, similar to compression seen for perisaccadic stimuli in human psychophysics. Second, neurons with distinct FF activity also showed suppression at the time of the saccade. The increase in FF activity and the decrease with suppression were temporally independent, making the patterns of activity difficult to separate. We resolved this by constructing a simple model with values for the start, peak, and duration of FF activity and suppression for each neuron. The model revealed the different time courses of FF sensitivity and suppression, suggesting that information about the impending saccade triggering suppression reaches the frontal eye field through a different pathway, or a different mechanism, than that triggering FF activity. Recognition of the variations in the time course of anticipatory FF activity provides critical information on its function and its relation to human visual perception at the time of the saccade. PMID- 24227736 TI - Microglial CD33-related Siglec-E inhibits neurotoxicity by preventing the phagocytosis-associated oxidative burst. AB - Sialic acid-binding Ig-like lectins (Siglecs) are members of the Ig superfamily that recognize sialic acid residues of glycoproteins. Siglec-E is a mouse CD33 related Siglec that preferentially binds to sialic acid residues of the cellular glycocalyx. Here, we demonstrate gene transcription and protein expression of Siglec-E by cultured mouse microglia. Siglec-E on microglia inhibited phagocytosis of neural debris and prevented the production of superoxide radicals induced by challenge with neural debris. Soluble extracellular Siglec-E receptor protein bound to the neural glycocalyx. Coculture of mouse microglia and neurons demonstrated a neuroprotective effect of microglial Siglec-E that was dependent on neuronal sialic acid residues. Increased neurotoxicity of microglia after knockdown of Siglece mRNA was neutralized by the reactive oxygen species scavenger Trolox. Data suggest that Siglec-E recognizes the intact neuronal glycocalyx and has neuroprotective function by preventing phagocytosis and the associated oxidative burst. PMID- 24227737 TI - Neural codes formed by small and temporally precise populations in auditory cortex. AB - The encoding of sensory information by populations of cortical neurons forms the basis for perception but remains poorly understood. To understand the constraints of cortical population coding we analyzed neural responses to natural sounds recorded in auditory cortex of primates (Macaca mulatta). We estimated stimulus information while varying the composition and size of the considered population. Consistent with previous reports we found that when choosing subpopulations randomly from the recorded ensemble, the average population information increases steadily with population size. This scaling was explained by a model assuming that each neuron carried equal amounts of information, and that any overlap between the information carried by each neuron arises purely from random sampling within the stimulus space. However, when studying subpopulations selected to optimize information for each given population size, the scaling of information was strikingly different: a small fraction of temporally precise cells carried the vast majority of information. This scaling could be explained by an extended model, assuming that the amount of information carried by individual neurons was highly nonuniform, with few neurons carrying large amounts of information. Importantly, these optimal populations can be determined by a single biophysical marker-the neuron's encoding time scale-allowing their detection and readout within biologically realistic circuits. These results show that extrapolations of population information based on random ensembles may overestimate the population size required for stimulus encoding, and that sensory cortical circuits may process information using small but highly informative ensembles. PMID- 24227738 TI - Electrical stimulation of the human homolog of the medial superior temporal area induces visual motion blindness. AB - Despite tremendous advances in neuroscience research, it is still unclear how neuronal representations of sensory information give rise to the contents of our perception. One of the first and also the most compelling pieces of evidence for direct involvement of cortical signals in perception comes from electrical stimulation experiments addressing the middle temporal (MT) area and the medial superior temporal (MST) area: two neighboring extrastriate cortical areas of the monkey brain housing direction-sensitive neurons. Here we have combined fMRI with electrical stimulation in a patient undergoing awake brain surgery, to separately probe the functional significance of the human homologs, i.e., area hMT and hMST, on motion perception. Both the stimulation of hMT and hMST made it impossible for the patient to perceive the global visual motion of moving random dot patterns. Although visual motion blindness was predominantly observed in the contralateral visual field, stimulation of hMST also affected the ipsilateral hemifield. These results suggest that early visual cortex up to the stage of MT is not sufficient for the perception of global visual motion. Rather, visual motion information must be mediated to higher-tier cortical areas, including hMST, to gain access to conscious perception. PMID- 24227739 TI - CRMP2 tethers kainate receptor activity to cytoskeleton dynamics during neuronal maturation. AB - The CRMP2 and CRMP4 proteins are strongly expressed in the developing nervous system, mediating neurite outgrowth, neuronal polarity, and axon guidance. In the present study, we demonstrate the interaction of the CRMP2 and CRMP4 proteins with the GluK5 subunit of the kainate (KA) receptor (KAR) and investigated the role of KARs in modulating the development of cultured mouse DRG neurons. We found that KARs modulate neuronal maturation and neurite outgrowth in a bidirectional manner. Accordingly, low concentrations of KA delayed maturation and enhanced neurite outgrowth, whereas maturation was promoted by higher concentrations of KA that attenuated neuritic elongation. The effects of weak KAR activation were prevented by blocking their noncanonical signaling and involved a differential regulation of CRMP2. Whereas the delay in maturation involves PKC mediated phosphorylation of CRMP2 at T555 leading to a downregulation of membrane Cav2.2, the promotion of neurite outgrowth is achieved by dephosphorylation at T514 at the growth cones, the latter reflecting PKC-driven enhancement of GSK3beta phosphorylation at S9. Together, these findings indicate that noncanonical KAR signaling influences neuronal development by modulating CRMP2 activity. PMID- 24227740 TI - Role of somatosensory cortex in visuospatial attention. AB - The human somatosensory cortex (S1) is not among the brain areas usually associated with visuospatial attention. However, such a function can be presumed, given the recently identified eye proprioceptive input to S1 and the established links between gaze and attention. Here we investigated a rare patient with a focal lesion of the right postcentral gyrus that interferes with the processing of eye proprioception without affecting the ability to locate visual objects relative to her body or to execute eye movements. As a behavioral measure of spatial attention, we recorded fixation time during visual search and reaction time for visual discrimination in lateral displays. In contrast to a group of age matched controls, the patient showed a gradient in looking time and in visual sensitivity toward the midline. Because an attention bias in the opposite direction, toward the ipsilesional space, occurs in patients with spatial neglect, in a second study, we asked whether the incidental coinjury of S1 together with the neglect-typical perisylvian lesion leads to a milder neglect. A voxelwise lesion behavior mapping analysis of a group of right-hemisphere stroke patients supported this hypothesis. The effect of an isolated S1 lesion on visual exploration and visual sensitivity as well as the modulatory role of S1 in spatial neglect suggest a role of this area in visuospatial attention. We hypothesize that the proprioceptive gaze signal in S1, although playing only a minor role in locating visual objects relative to the body, affects the allocation of attention in the visual space. PMID- 24227741 TI - Synapsin II and Rab3a cooperate in the regulation of epileptic and synaptic activity in the CA1 region of the hippocampus. AB - Some forms of idiopathic epilepsy in animals and humans are associated with deficiency of synapsin, a phosphoprotein that reversibly associates with synaptic vesicles. We have previously shown that the epileptic phenotype seen in synapsin II knock-out mice (SynII(-)) can be rescued by the genetic deletion of the Rab3a protein. Here we have examined the cellular basis for this rescue using whole cell recordings from CA1 hippocampal pyramidal cells in brain slices. We find that SynII(-) neurons have increased spontaneous activity and a reduced threshold for the induction of epileptiform activity by 4-aminopyridine (4-AP). Using selective recordings of glutamatergic and GABAergic activity we show that in wild type neurons low concentrations of 4-AP facilitate glutamatergic and GABAergic transmission in a balanced way, whereas in SynII(-) neurons this balance is shifted toward excitation. This imbalance reflects a deficit in inhibitory synaptic transmission that appears to be secondary to reduced Ca(2+) sensitivity in SynII(-) neurons. This suggestion is supported by our finding that synaptic and epileptiform activity at SynII(-) and wild-type synapses is similar when GABAergic transmission is blocked. Deletion of Rab3a results in glutamatergic synapses that have a compromised responsiveness to either low 4-AP concentrations or elevated extracellular Ca(2+). These changes mitigate the overexcitable phenotype observed in SynII(-) neurons. Thus, Rab3a deletion appears to restore the excitatory/inhibitory imbalance observed in SynII(-) hippocampal slices indirectly, not by correcting the deficit in GABAergic synaptic transmission but rather by impairing excitatory glutamatergic synaptic transmission. PMID- 24227742 TI - Glial control of endocannabinoid heterosynaptic modulation in hypothalamic magnocellular neuroendocrine cells. AB - Cannabinoid receptors are functionally operant at both glutamate and GABA synapses on hypothalamic magnocellular neuroendocrine cells; however, retrograde endocannabinoid actions are evoked at only glutamate synapses. We tested whether the functional targeting of evoked retrograde endocannabinoid actions to glutamate, and not GABA, synapses on magnocellular neurons is the result of the spatial restriction of extracellular endocannabinoids by astrocytes. Whole-cell GABA synaptic currents were recorded in magnocellular neurons in rat hypothalamic slices following manipulations to reduce glial buffering of extracellular signals. Depolarization- and glucocorticoid-evoked retrograde endocannabinoid suppression of synaptic GABA release was not detected under normal conditions, but occurred in both oxytocin and vasopressin neurons under conditions of attenuated glial coverage and depressed glial metabolic function, suggesting an emergent endocannabinoid modulation of GABA synapses with the loss of astrocyte function. Tonic endocannabinoid suppression of GABA release was insensitive to glial manipulation. Blocking cannabinoid transport mimicked, and increasing the extracellular viscosity reversed, the effect of suppressed glial buffering on the endocannabinoid modulation of GABA release. Evoked, but not tonic, endocannabinoid modulation of GABA synapses was mediated by 2 arachidonoylglycerol. Therefore, depolarization- and glucocorticoid-evoked 2 arachidonoylglycerol release from magnocellular neurons is spatially restricted to glutamate synapses by astrocytes, but spills over onto GABA synapses under conditions of reduced astrocyte buffering; tonic endocannabinoid modulation of GABA release, in contrast, is likely mediated by anandamide and is insensitive to astrocytic buffering. Astrocytes, therefore, provide dynamic control of stimulus evoked 2-arachidonoylglycerol, but not tonic anandamide, regulation of GABA synaptic inputs to magnocellular neuroendocrine cells under different physiological conditions. PMID- 24227743 TI - Fast hemodynamic responses in the visual cortex of the awake mouse. AB - Hemodynamic responses in mice and other species are typically measured under anesthesia. However, anesthesia could influence their relationship to neural activity. To investigate this relationship, we used optical imaging in mouse primary visual cortex (V1). Hemodynamic responses yielded clear maps of retinotopy in both anesthetized and awake mice. However, during wakefulness, responses were four times larger and twice as fast. These differences held whether we induced anesthesia with urethane or isoflurane and whether awake mice were stationary or running on a treadmill. With electrode recordings, we established that the effects of wakefulness reflect changes in neurovascular coupling, not in neural activity. By activating V1 directly via optogenetics, we replicated the effects of wakefulness in terms of timing but not of amplitude. We conclude that neurovascular coupling depends critically on anesthesia and wakefulness: during wakefulness, neural activity is followed by much stronger and quicker hemodynamic responses. PMID- 24227744 TI - Black carbon accrual during 2000 years of paddy-rice and non-paddy cropping in the Yangtze River Delta, China. AB - Rice straw burning has accompanied paddy management for millennia, introducing black carbon (BC) into soil as the residue of incomplete combustion. This study examined the contribution of BC to soil organic matter and the rate at which it accumulates in paddy soils as a result of prolonged paddy management. Soil depth profiles were sampled along a chronosequence of 0-2000 years of rice-wheat rotation systems and adjacent non-paddy systems (50-700 years) in the Bay of Hangzhou (Zhejiang province, China). The soil BC content and its degree of condensation were assessed using benzene-polycarboxylic acids (BPCAs) as geochemical markers. The results showed that despite regular long term BC input, BC only contributed 7-11% of total soil organic carbon (SOC) in the topsoil horizons. Nevertheless, along with SOC, paddy soils accumulated BC with increasing duration of management until 297 years to reach a steady-state of 13 t BC ha(-1). This was 1.8 times more than in non-paddy soils. The fate of BC in paddy soils (0-1 m) could be modeled revealing an average annual input of 44 kg ha(-1) yr(-1), and a mean residence time of 303 years. The subsoils contributed at least 50% to overall BC stocks, which likely derived from periods prior to land embankment and episodic burial of ancient topsoil, as also indicated by BPCA pattern changes. We conclude that there is a significant but limited accumulation of C in charred forms upon prolonged paddy management. The final contribution of BC to total SOC in paddy soils was similar to that in other aerobic ecosystems of the world. PMID- 24227745 TI - Abnormal photocurrent response and enhanced photocatalytic activity induced by charge transfer between WS(2) nanosheets and WO(3) nanoparticles. AB - Sun trap: Pure WS2 nanosheets are prepared that exhibit excellent photosensitive properties. After functionalization with WO3 nanoparticles, abnormal photocurrent responses, enhanced photocatalytic activity, and induced photoluminescence is observed. PMID- 24227746 TI - Microarray platform affords improved product analysis in mammalian cell growth studies. AB - High throughput (HT) platforms serve as a cost-efficient and rapid screening method for evaluating the effect of cell-culture conditions and screening of chemicals. We report the development of a HT cell-based microarray platform to assess the effect of culture conditions on Chinese hamster ovary (CHO) cells. Specifically, growth, transgene expression and metabolism of a GS/methionine sulphoximine (MSX) CHO cell line, which produces a therapeutic monoclonal antibody, was examined using a microarray system in conjunction with a conventional shake flask platform in a non-proprietary medium. The microarray system consists of 60-nL spots of cells encapsulated in alginate and separated in groups via an 8-well chamber system attached to the chip. Results show the non proprietary medium developed allows cell growth, production, and normal glycosylation of recombinant antibody and metabolism of the recombinant CHO cells in both the microarray and shake flask platforms. In addition, 10.3 mM glutamate addition to the defined base medium results in lactate metabolism shift in the recombinant GS/MSX CHO cells in the shake flask platform. Ultimately, the results demonstrate that the HT microarray platform has the potential to be utilized for evaluating the impact of media additives on cellular processes, such as cell growth, metabolism, and productivity. PMID- 24227747 TI - Does spatial ability help the learning of anatomy in a biomedical science course? AB - A three-dimensional appreciation of the human body is the cornerstone of clinical anatomy. Spatial ability has previously been found to be associated with students' ability to learn anatomy and their examination performance. The teaching of anatomy has been the subject of major change over the last two decades with the reduction in time spent on dissection and greater use of web based and computer-based resources. In this study, we examine whether the relationship between spatial ability and performance in anatomy examinations is sustained in a contemporary curriculum. A comparison of students' performance in a series of tests of spatial ability to their anatomy examination scores in biomedical sciences course exhibited only weak association (r = 0.145 and P = 0.106). This has implications for the use of spatial ability as a predictor of success in introductory subjects in the teaching of anatomy. PMID- 24227749 TI - Cyclopalladation and reactivity of amino esters through C-H bond activation: experimental, kinetic, and density functional theory mechanistic studies. AB - The orthopalladation, through C-H bond activation, of a large number of amino esters and amino phosphonates derived from phenylglycine, and having different substituents at the aryl ring and the C-alpha atom, as well as on the N-amine atom, has been studied. The experimental observations indicated an improvement in the yields of the orthopalladated compounds when the N-amine and/or the C-alpha atom are substituted, when compared with the unsubstituted methyl phenylglycinate derivatives. In contrast, substitutions at the aryl ring do not promote significant changes in the orthometalation results. Furthermore, the use of hydrochloride salts of the amino esters has also been shown to have a remarkably favorable effect on the process. All these observations have been fully quantified at different temperatures and pressures by a detailed kinetic study in solution in different solvents and in the presence and absence of added Bronsted acids and chloride anions. The data collected indicate relevant changes in the process depending on these conditions, as expected from the general background known for cyclopalladation reactions. An electronic mechanism of the orthopalladation has been proposed based on DFT calculations at the B3LYP level, and a very good agreement between the trends kinetically measured and the theoretically calculated activation barriers has been obtained. The reactivity of the new orthopalladated amino phosphonate derivatives has been tested and it was found that their halogenation, alkoxylation and carbonylation resulted in formation of the corresponding functionalized ortho-haloaminophosphonates, ortho alkoxyaminophosphonates and oxoisoindolinylphosphonates. PMID- 24227748 TI - Caring about prognosis: a validation study of the caring criteria to identify hospitalized patients at high risk for death at 1 year. AB - BACKGROUND: Identifying patients, at the time of hospital admission, who are at high risk for 1-year mortality is an ideal opportunity to introduce palliative interventions into the hospital care plan. The CARING (C = primary diagnosis of cancer, A = >= 2 admissions to the hospital for a chronic illness within the last year; R = resident in a nursing home; I = intensive care unit admission with multiorgan failure, NG = noncancer hospice guidelines [meeting >= 2 of the National Hospice and Palliative Care Organization's guidelines] criteria is a practical prognostic index developed and validated in the Veteran's Administration hospital setting that identifies patients at high risk of death within 1 year, although its effectiveness in a broader patient population is unknown. OBJECTIVE: To validate the CARING criteria in a university and safety net hospital setting. DESIGN: Retrospective observational cohort study. SETTING: Inpatient. PATIENTS: Adults admitted to medical and surgical inpatient services during the study period of July 2005 through August 2005. MEASUREMENTS: Mortality at 1 year following the index hospitalization was the primary end point. The CARING criteria were abstracted from the chart using only medical data available at time of admission. RESULTS: At total of 1064 patients were admitted during the study period. Primary diagnosis of cancer (odds ratio [OR) = 7.23 [4.45-11.75]), intensive care unit admission with multiple organ failure (OR = 6.97 [2.75 17.68]), >2 noncancer hospice guidelines (OR = 15.55 [7.28-33.23]), and age (OR = 1.60 [1.32-1.93]) were predictive of 1-year mortality (C statistic = 0.79). One year survival was significantly lower for those who met >= 1 of the CARING criteria. CONCLUSIONS: The CARING criteria are a practical prognostic tool validated in a broad inpatient population that can be utilized on hospital admission to estimate risk of death in 1 year, with the goal of identifying patients who may benefit most from incorporating palliative interventions into their hospital plan of care. Journal of Hospital Medicine 2013;8:696-701. (c) 2013 Society of Hospital Medicine. PMID- 24227750 TI - Study of intermolecular interactions in the corrole matrix by solid-state NMR under 100 kHz MAS and theoretical calculations. PMID- 24227751 TI - A blueprint for cost-efficient localization microscopy. AB - Crystal clear: The authors introduce a miniaturized localization microscopy setup based on cost-effective components. They demonstrate its feasibility for subdiffraction resolution fluorescence imaging in resolving different cellular nanostructures. The setup can be used advantageously in practical courses for training students in super-resolution fluorescence microscopy. PMID- 24227752 TI - Aging results in molecular changes in an enriched population of undifferentiated rat spermatogonia. AB - A strong correlation exists between increasing paternal age and a decline in reproductive function. Testis aging is associated with testicular atrophy, increased DNA damage, and de novo mutations. It is unclear whether these problems arise from the spermatogonial stem cells (SSCs), a buildup of anomalies as older germ cells progress through spermatogenesis, or both. We hypothesize that with the continual divisions of SSCs that maintain the germ cell population, an alteration of these cells occurs over time. To test this, we utilized young (4-mo old) and aged (18- and 21-mo-old) transgenic rats that express GFP in germ cells only. We first examined the number and activity of SSCs from the different age groups by transplantation. Aged rats had numerically fewer SSCs than young rats (<50%; not significant) despite the lack of testicular atrophy, and 21-mo-old rats show a significant reduction in colony length, suggesting that the quality of SSCs also deteriorates. To evaluate any molecular changes occurring in the early cells of spermatogenesis with age, we isolated an SSC-enriched population of CD9-positive (CD9(+)) cells using fluorescence-activated cell sorting (confirmed by transplantation studies) and extracted RNA for microarray analysis. In the aged CD9(+) cells, 60 transcripts were upregulated and more than 500 downregulated compared to the young cells. An altered expression was found for transcripts involved in mitosis and in DNA damage response. These results suggest molecular alterations in the SSC-enriched population of aged CD9(+) cells, implying that reproductive aging originates in the undifferentiated cells of spermatogenesis. PMID- 24227753 TI - Multicolor flow cytometry and nanoparticle tracking analysis of extracellular vesicles in the plasma of normal pregnant and pre-eclamptic women. AB - Excessive release of syncytiotrophoblast extracellular vesicles (STBMs) from the placenta into the maternal circulation may contribute to the systemic inflammation that is characteristic of pre-eclampsia (PE). Other intravascular cells types (platelets, leukocytes, red blood cells [RBCs], and endothelium) may also be activated and release extracellular vesicles (EVs). We developed a multicolor flow cytometry antibody panel to enumerate and phenotype STBMs in relation to other EVs in plasma from nonpregnant (NonP) and normal pregnant (NormP) women, and women with late-onset PE. Nanoparticle tracking analysis (NTA) was used to determine EV size and concentration. In vitro-derived STBMs and EVs from platelets, leukocytes, RBCs, and endothelial cells were examined to select suitable antibodies to analyze the corresponding plasma EVs. Flow cytometry analysis of plasma from NonP, NormP, and PE showed that STBMs comprised the smallest group of circulating EVs, whereas most were derived from platelets. The next most abundant group comprised unidentified orphan EVs (which did not label with any of the antibodies in the panel), followed by EVs from RBCs and leukocytes. NTA showed that the total number of EVs in plasma was significantly elevated in NormP and late-onset PE women compared to NonP controls, and that EVs were smaller in size. In general, EVs were elevated in pregnancy plasma apart from platelet EVs, which were reduced. These studies did not show any differences in EVs between NormP and PE, probably because late-onset PE was studied. PMID- 24227754 TI - Differential incubation temperatures result in dimorphic DNA methylation patterning of the SOX9 and aromatase promoters in gonads of alligator (Alligator mississippiensis) embryos. AB - Environmental factors are known to influence sex determination in many nonmammalian vertebrates. In all crocodilians studied thus far, temperature is the only known determinant of sex. However, the molecular mechanisms mediating the effect of temperature on sex determination are not known. Aromatase (CYP19A1) and SOX9 play critical roles in vertebrate sex determination and gonadogenesis. Here, we used a variety of techniques to investigate the potential roles of DNA methylation patterning on CYP19A1 and SOX9 expression in the American alligator, an organism that relies on temperature-dependent sex determination. Our findings reveal that developing gonads derived from embryos incubated at a male-producing temperature (MPT) show elevated CYP19A1 promoter methylation and decreased levels of gene expression relative to incubation at a female-producing temperature (FPT). The converse was observed at the SOX9 locus, with increased promoter methylation and decreased expression occurring in embryonic gonads resulting from incubation at FPT relative to that of MPT. We also examined the gonadal expression of the three primary, catalytically active DNA methyltransferase enzymes and show that they are present during critical stages of gonadal development. Together, these data strongly suggest that DNA methylation patterning is a central component in coordinating the genetic cascade responsible for sexual differentiation. In addition, these data raise the possibility that DNA methylation could act as a key mediator integrating temperature into a molecular trigger that determines sex in the alligator. PMID- 24227756 TI - Fibroblast growth factor receptor two (FGFR2) regulates uterine epithelial integrity and fertility in mice. AB - Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate luminal epithelial (LE) cell proliferation in the adult mouse uterus. This study tested the hypothesis that FGFR2 has a biological role in postnatal development and function of the uterus by conditionally deleting Fgfr2 after birth using progesterone receptor (Pgr)-Cre mice. Adult Fgfr2 mutant female mice were initially subfertile and became infertile with increasing parity. No defects in uterine gland development were observed in conditional Fgfr2 mutant mice. In the adult, Fgfr2 mutant mice possessed a histologically normal reproductive tract with the exception of the uterus. The LE of the Fgfr2 mutant uterus was stratified, but no obvious histological differences were observed in the glandular epithelium, stroma, or myometrium. Within the stratified LE, cuboidal basal cells were present and positive for basal cell markers (KRT14 and TRP63). Nulliparous bred Fgfr2 mutants contained normal numbers of blastocysts on Day 3.5 postmating, but the number of embryo implantation sites was substantially reduced on Day 5.5 postmating. These results support the idea that loss of FGFR2 in the uterus after birth alters its development, resulting in LE stratification and peri-implantation pregnancy loss. PMID- 24227758 TI - Decidualized human endometrial stromal cells are sensors of hormone withdrawal in the menstrual inflammatory cascade. AB - Menstruation is a complex process dependent on premenstrual release of inflammatory mediators and proteolytic enzymes from endometrial cells. Endometrial leukocytes are traditionally considered to be the major source of the inflammatory factors. However, evidence is emerging to suggest a role for decidualized endometrial stromal cells in the premenstrual inflammatory cascade. We sought to determine if withdrawal of hormone support (estrogen and progesterone) from decidualized endometrial stromal cells, in a model mimicking the precise timing leading to menstruation, activated inflammatory signaling pathways and downstream release of inflammatory mediators. Human endometrial stromal cells decidualized gradually over 12 days of estradiol and progestin treatment as evidenced by an increase in prolactin secretion. Withdrawal of hormone support from decidualized stromal cells resulted in a decrease in cytoplasmic IkappaB and a progressive increase in nuclear accumulation of NF kappaB, as demonstrated by Western immunoblot and immunocytochemical analyses. Concomitant with nuclear translocation of NF-kappaB, hormone withdrawal led to production of a host of inflammatory mediators by the decidualized stromal cells, including IFN-alpha, IL-6, CCL11, GM-CSF, CCL2, IL1-RA, CXCL10, CXCL8, IL-12, IL 15, VEGF, and CCL5. Elevation of inflammatory mediators was not observed, however, upon hormone withdrawal in cells treated with the NF-kappaB inhibitor BAY 11-7085. Decidualized stromal cells are likely highly sensitive sensors of changing hormone levels. This provides a mechanism by which decidualized stromal cells may recruit inflammatory leukocytes into the premenstrual endometrium and contribute to the intense inflammation underlying this unique physiological process. PMID- 24227759 TI - Resting-state fMRI study on drug-naive patients with Parkinson's disease and with depression. AB - OBJECTIVE: This study used resting-state functional MRI (fMRI) to evaluate regional and network alterations in patients with Parkinson's disease (PD) with and without depression. METHOD: We recruited 29 patients with PD with depression (PD-Dep), 30 patients with PD without depression (PD-NDep), and 30 normal controls. All participants underwent resting-state fMRI scans on a 3-T MR system. The amplitude of low-frequency fluctuation (ALFF) of blood oxygen level-dependent signals was used to characterise regional cerebral function. Functional integration of the brain network was evaluated by seed-based correlation approach. RESULTS: The PD-Dep group showed significantly higher ALFF value in the left orbitofrontal area compared with both the PD-NDep and control groups (p<0.05 corrected by FWE). In patients with PD, the Hamilton Depression Rating Scale score was positively correlated with the ALFF value in the left orbitofrontal cortex (p<0.005 uncorrected). Brain network connectivity analysis revealed reduced functional connectivity of putamen in both PD subgroups. However, the PD Dep group showed more distributed reduced connectivity in the prefrontal-limbic network than the PD-NDep group did (p<0.05 corrected by FWE). CONCLUSIONS: Our study demonstrates that PD-Dep patients are characterised by increased regional spontaneous neural activity in the orbitofrontal area and decreased functional integration within the prefrontal-limbic network. These findings may be helpful for facilitating further understanding of the potential mechanisms underlying depression in PD. PMID- 24227755 TI - How the kidney is impacted by the perinatal maternal environment to develop hypertension. AB - Environmental conditions during perinatal development such as maternal undernutrition, maternal glucocorticoids, placental insufficiency, and maternal sodium overload can program changes in renal Na(+) excretion leading to hypertension. Experimental studies indicate that fetal exposure to an adverse maternal environment may reduce glomerular filtration rate by decreasing the surface area of the glomerular capillaries. Moreover, fetal responses to environmental insults during early life that contribute to the development of hypertension may include increased expression of tubular apical or basolateral membrane Na(+) transporters and increased production of renal superoxide leading to enhanced Na(+) reabsorption. This review will address the role of these potential renal mechanisms in the fetal programming of hypertension in experimental models induced by maternal undernutrition, fetal exposure to glucocorticoids, placental insufficiency, and maternal sodium overload in the rat. PMID- 24227761 TI - Approach to the adult hospitalized patient on an insulin pump. AB - Patients on continuous subcutaneous insulin infusion, or insulin pumps, are increasingly seen in hospitals. Inpatient providers need to have a working knowledge of insulin pumps to be able to decide, in conjunction with the patient whenever feasible, whether or not pump use is to be continued in the hospital, to assist patients in adjusting insulin doses via continuous subcutaneous insulin infusion, to transition patients to multiple daily subcutaneous insulin dosing as appropriate, and to prevent or manage problems that might arise from improper handling of the insulin pump. Clinical vignettes with key points and strategies for patient care are discussed in this article. PMID- 24227760 TI - Histone deacetylase inhibitors with enhanced enzymatic inhibition effects and potent in vitro and in vivo antitumor activities. AB - In the present work, a series of small molecules were designed and synthesized based on structural optimization. A significant improvement in the enzyme inhibitory activity of these compounds was discovered. Moreover, the tested compounds have moderate preference for class I HDACs over HDAC6, as demonstrated by enzyme selectivity assays. In vitro antiproliferation assay results show that representative compounds can selectively inhibit the growth of non-solid lymphoma and leukemic cells such as U937, K562, and HL60. In the in vivo antitumor assay, (S)-4-(2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-phenylacetamido)-N hydroxybenzamide (D17) showed better performance than SAHA in blocking U937 tumor growth. Western blot analysis revealed that representative molecules can block the function of both class I HDACs and HDAC6. More importantly, our western blot results reveal that the levels of some oncogenic proteins (p-Akt in the PI3K/AKT/mTOR signal pathway, c-Raf and p-Erk in the MAPK signal pathway) were dramatically down-regulated by our compounds in the U937 cell line rather than MDA-MB-231 cells. This distinction in cellular mechanism might be an important reason why the U937 cell line was found to more sensitive to our HDAC inhibitors than the MDA-MB-231 cell line. PMID- 24227762 TI - An overview of the roles and responsibilities of Chinese medical colleges in body donation programs. AB - The use of human tissue is critical for gross anatomy education in the health professions. Chinese medical colleges have faced a shortage of anatomical specimens over the past decade. While body donation plays an important role in overcoming this gap, this practice has only recently been introduced in China, and the donation rate is relatively low and fraught with a number of difficulties. In the past, traditional Chinese culture focused on preserving the human body intact, which often limited body donation. In recent years, the public has become more open toward body donation. At Nanjing Medical University, only 20 bodies were donated in 2001. After the university became involved in an organized body donation program, this number increased to 70 donated bodies per year (2007 to 2012). This article describes and reviews Chinese medical colleges as a special case study among body donation programs, particularly in terms of the multiple responsibilities and roles that such institutions must assume in the course of adopting these programs. Medical colleges in China must serve as advocates, coordinators, builders, managers, educators, and beneficiaries in undertaking body donation programs. It is important for medical colleges to recognize these pluripotent roles and educate the public in order to promote body donation programs. This case study may also effectively guide and encourage Chinese medical colleges in refining their own body donation programs in the future. PMID- 24227763 TI - Exploring the experience of hearing voices from a first person perspective: a meta-ethnographic synthesis. AB - PURPOSE: The purpose of this review was to identify, appraise, and synthesize the current peer-reviewed qualitative literature which explores the phenomenon of hearing voices from a first person perspective. METHODS: A comprehensive systematic search of the literature was conducted. Seven studies utilizing various qualitative methodologies met the criteria to be included in the synthesis. An appraisal tool (Walsh & Downe, 2005, J. Adv. Nurs., 50, 204-211) was used to assess their quality. A meta-ethnographic approach was used to synthesize the data extracted from them. RESULTS: The interpretation of the findings suggested five key themes: identity of the voice(s), power of the voice(s), impact of hearing voices on relationships, relationship with the voice(s), and the distinction between thoughts and voices. The identity of the voices seemed inextricably linked to the perceived power the voice(s) wielded over the voice hearer. The quality of the studies included in the synthesis varied greatly. CONCLUSIONS: The findings of this synthesis highlight the importance of the voice hearer's individual frame of reference for understanding their experience. Clinical implications include the need for mental health professionals to explore an individual's understanding of their experience of hearing voices and address the perceived power of the voice(s). Further research is indicated in this area with a focus of improving the quality of qualitative research studying this phenomenon. PRACTITIONER POINTS: There are multiple frames of reference in which to understand an individual's experience of hearing voices. Mental health professionals should attend to the meaning and understanding voice hearers give to the experience. PMID- 24227764 TI - Design, synthesis, and X-ray crystal structure of a fullerene-linked metal organic framework. AB - Given the unique structural and electronic properties of C60 , metal-organic frameworks (MOFs) containing C60 linkers are expected to exhibit interesting characteristics. A new hexakisfullerene derivative possessing two pairs of phenyl pyridine groups attached to two methano-carbon atoms located at the trans-1 positions was designed and synthesized. The four pyridyl nitrogen atoms define a perfectly planar rectangle. This new C60 derivative was used to assemble the first fullerene-linked two-dimensional MOF by coordination with Cd(2+) . PMID- 24227765 TI - Surface supported gold-organic hybrids: on-surface synthesis and surface directed orientation. AB - The surface-assisted synthesis of gold-organic hybrids on Au (111) and Au (100) surfaces is repotred by thermally initiated dehalogenation of chloro-substituted perylene-3,4,9,10-tetracarboxylic acid bisimides (PBIs). Structures and surface directed alignment of the Au-PBI chains are investigated by scanning tunnelling microscopy in ultra high vacuum conditions. Using dichloro-PBI as a model system, the mechanism for the formation of Au-PBI dimer is revealed with scanning tunnelling microscopy studies and density functional theory calculations. A PBI radical generated from the homolytic C-Cl bond dissociation can covalently bind a surface gold atom and partially pull it out of the surface to form stable PBI-Au hybrid species, which also gives rise to the surface-directed alignment of the Au PBI chains on reconstructed Au (100) surfaces. PMID- 24227766 TI - Cadaver CT scans a useful adjunct in gross anatomy: The medical student perspective. PMID- 24227767 TI - PPh3-catalyzed ring-expansion reactions of sulfamate-derived cyclic imines with acetylenedicarboxylates. AB - The PPh3-catalyzed ring-expansion reaction of sulfamate-derived cyclic imines with acetylenedicarboxylates has been developed. The reaction works quite efficiently under very mild conditions to afford benzo[g][1,2,3]oxathiazocine-4,5 dicarboxylate 2,2-dioxide derivatives in high yields. PMID- 24227769 TI - Tadalafil for benign prostatic hyperplasia: an update. PMID- 24227770 TI - Management of hyperemesis gravidarum. AB - Nausea and vomiting in pregnancy are common complaints and vary considerably in duration and severity. Hyperemesis gravidarum represents the extreme end of the spectrum associated with dehydration and weight loss. As embryonic organogenesis occurs during the first trimester, pharmacological intervention for any condition during this period poses a significant clinical dilemma requiring careful assessment of risks and benefits. In the UK, there are no formal national guidelines for the management of hyperemesis gravidarum. In addition, no high quality evidence exists for i.v. fluid and electrolyte replacement in hyperemesis gravidarum, and a Cochrane review on interventions for the treatment of nausea and vomiting in pregnancy specifically excluded studies on hyperemesis gravidarum. In this article, we review the evidence for the efficacy and safety of different management options for hyperemesis gravidarum. PMID- 24227768 TI - A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine. AB - Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical MU-opioid agonist, morphine. Healthy, out-of-treatment opioid dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID- 24227771 TI - Linaclotide for constipation-predominant IBS. AB - Irritable bowel syndrome is a chronic relapsing disorder characterised by abdominal pain or discomfort associated with defaecation, abdominal bloating and a change in bowel habit. IBS may be classified by the change in bowel function as 'diarrhoea predominant' (IBS-D), 'constipation predominant' (IBS-C) or mixed, or may be unclassified. Although it is not thought to be associated with the development of serious disease, IBS is a debilitating condition often resulting in reduced quality of life and significant use of healthcare resources. Current drug treatment strategies target the patient's predominant symptoms and typically involve the use of an antispasmodic and either a laxative or antidiarrhoeal agent. Linaclotide (Constella-Almirall) is an oral guanylate cyclase-C receptor agonist licensed for the symptomatic treatment of moderate to severe IBS-C in adults. In this article, we consider the evidence for linaclotide and how its use fits with current management strategies for IBS-C. PMID- 24227772 TI - MicroRNA-155 tunes both the threshold and extent of NK cell activation via targeting of multiple signaling pathways. AB - NK cells are innate lymphocytes important for host defense against viral infections and malignancy. However, the molecular programs orchestrating NK cell activation are incompletely understood. MicroRNA-155 (miR-155) is markedly upregulated following cytokine activation of human and mouse NK cells. Surprisingly, mature human and mouse NK cells transduced to overexpress miR-155, NK cells from mice with NK cell-specific miR-155 overexpression, and miR-155(-/-) NK cells all secreted more IFN-gamma compared with controls. Investigating further, we found that activated NK cells with miR-155 overexpression had increased per-cell IFN-gamma with normal IFN-gamma(+) percentages, whereas greater percentages of miR-155(-/-) NK cells were IFN-gamma(+). In vivo murine CMV-induced IFN-gamma expression by NK cells in these miR-155 models recapitulated the in vitro phenotypes. We performed unbiased RNA-induced silencing complex sequencing on wild-type and miR-155(-/-) NK cells and found that mRNAs targeted by miR-155 were enriched in NK cell activation signaling pathways. Using specific inhibitors, we confirmed these pathways were mechanistically involved in regulating IFN-gamma production by miR-155(-/-) NK cells. These data indicate that miR-155 regulation of NK cell activation is complex and that miR-155 functions as a dynamic tuner for NK cell activation via both setting the activation threshold as well as controlling the extent of activation in mature NK cells. In summary, miR-155(-/-) NK cells are more easily activated, through increased expression of proteins in the PI3K, NF-kappaB, and calcineurin pathways, and miR-155(-/-) and 155-overexpressing NK cells exhibit increased IFN-gamma production through distinct cellular mechanisms. PMID- 24227773 TI - MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. AB - Recent research has indicated a new mode of intercellular communication facilitated by the movement of RNA between cells. There is evidence that RNA can transfer between cells in a multitude of ways, including in complex with proteins or lipids or in vesicles, including apoptotic bodies and exosomes. However, there remains little understanding of the function of nucleic acid transfer between human cells. In this article, we report that human macrophages transfer microRNAs (miRNAs) to hepato-carcinoma cells (HCCs) in a manner that required intercellular contact and involved gap junctions. Two specific miRNAs transferred efficiently between these cells--miR-142 and miR-223--and both were endogenously expressed in macrophages and not in HCCs. Transfer of these miRNAs influenced posttranscriptional regulation of proteins in HCCs, including decreased expression of reporter proteins and endogenously expressed stathmin-1 and insulin like growth factor-1 receptor. Importantly, transfer of miRNAs from macrophages functionally inhibited proliferation of these cancerous cells. Thus, these data led us to propose that intercellular transfer of miRNA from immune cells could serve as a new defense against unwanted cell proliferation or tumor growth. PMID- 24227774 TI - In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit. AB - The programmed cell death-1 (PD-1)/programmed cell death ligand-1 pathway has been shown to limit cell-mediated effector functions during chronic viral infections impeding clearance of pathogens. As a strategy to reverse this exhaustion and increase T cell polyfunctionality, PD-1 ligands were blocked in vivo using a recombinant macaque PD-1 fused to a macaque Ig-Fc (rPD-1-Fc) in SIVmac239-infected rhesus macaques during the early chronic phase of infection, either alone or in combination with antiretroviral therapy. In vitro blockade showed improvement of Ag-specific CD4(+) and CD8(+) T cells from monkeys chronically infected with SIV. Of note, a prolonged 5-d blockade in culture was beneficial for both gag-specific CD4(+) and CD8(+) T cells based on proliferation and dual cytokine production. Although the in vivo administration of rPD-1-Fc induced enhanced SIV-specific CD4 and CD8 T cell proliferation both in the blood and gut, it failed to alter plasma viremia. However, rPD-1-Fc administration in the context of antiretroviral therapy interruption induced a significant delay of viral load rebound. In addition, rPD-1-Fc administration in MamuA*001(+) monkeys led to both an increase in the frequencies and Ki67 expression of GagCM9(+) CD8(+) T cells in the blood and rectal mucosa and polyfunctionality of GagCM9(+) CD8(+) T cells in blood. In conclusion, however, our data suggest that PD 1/programmed cell death ligand-1 blockade using soluble rPD-1-Fc instead of anti PD-1 mAb, although effective in rescuing the effector function of SIV-specific CD4(+) and CD8(+) T cells during the early chronic phase of infection, has limited clinical benefit. PMID- 24227775 TI - Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8alpha+ dendritic cell development. AB - Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8(-/-) bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8alpha(+) DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8alpha(+) DC specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8alpha(+) DCs. We show that, without Irf8, expression of Id2 and Batf3 was not sufficient for directing classical CD8alpha(+) DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8alpha(+) DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8alpha(+) DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8alpha(+) DC development. PMID- 24227777 TI - Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells. AB - The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS specific BMEM with comparable effect to the cognate T cells available to TT specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued. PMID- 24227776 TI - Epithelial NF-kappaB orchestrates house dust mite-induced airway inflammation, hyperresponsiveness, and fibrotic remodeling. AB - NF-kappaB activation within the epithelium has been implicated in the pathogenesis of asthma, yet the exact role of epithelial NF-kappaB in allergen induced inflammation and airway remodeling remains unclear. In the current study, we used an intranasal house dust mite (HDM) extract exposure regimen time course in BALB/c mice to evaluate inflammation, NF-kappaB activation, airway hyperresponsiveness (AHR), and airway remodeling. We used CC10-IkappaBalphaSR transgenic mice to evaluate the functional importance of epithelial NF-kappaB in response to HDM. After a single exposure of HDM, mRNA expression of proinflammatory mediators was significantly elevated in lung tissue of wild-type (WT) mice, in association with increases in nuclear RelA and RelB, components of the classical and alternative NF-kappaB pathway, respectively, in the bronchiolar epithelium. In contrast, CC10-IkappaBalphaSR mice displayed marked decreases in nuclear RelA and RelB and mRNA expression of proinflammatory mediators compared with WT mice. After 15 challenges with HDM, WT mice exhibited increases in inflammation, AHR, mucus metaplasia, and peribronchiolar fibrosis. CC10 IkappaBalphaSR transgenic mice displayed marked decreases in neutrophilic infiltration, tissue damping, and elastance parameters, in association will less peribronchiolar fibrosis and decreases in nuclear RelB in lung tissue. However, central airway resistance and mucus metaplasia remained elevated in CC10 IkappaBalphaSR transgenic mice, in association with the continued presence of lymphocytes, and partial decreases in eosinophils and IL-13. The current study demonstrates that following airway exposure with an asthma-relevant allergen, activation of classical and alternative NF-kappaB pathways occurs within the airway epithelium and may coordinately contribute to allergic inflammation, AHR, and fibrotic airway remodeling. PMID- 24227778 TI - Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor. AB - Focal adhesion kinase (FAK) is a critical regulator of signal transduction in multiple cell types. Although this protein is activated upon TCR engagement, the cellular function that FAK plays in mature human T cells is unknown. By suppressing the function of FAK, we revealed that FAK inhibits TCR-mediated signaling by recruiting C-terminal Src kinase to the membrane and/or receptor complex following TCR activation. Thus, in the absence of FAK, the inhibitory phosphorylation of Lck and/or Fyn is impaired. Together, these data highlight a novel role for FAK as a negative regulator TCR function in human T cells. These results also suggest that changes in FAK expression could modulate sensitivity to TCR stimulation and contribute to the progression of T cell malignancies and autoimmune diseases. PMID- 24227779 TI - Disturbed follicular architecture in B cell A disintegrin and metalloproteinase (ADAM)10 knockouts is mediated by compensatory increases in ADAM17 and TNF-alpha shedding. AB - B cell A disintegrin and metalloproteinase 10 (ADAM10) is required for the development and maintenance of proper secondary lymphoid tissue architecture; however, the underlying mechanism remains unclear. In this study, we show disturbances in naive lymph node architecture from B cell-specific ADAM10 deficient mice (ADAM10(B-/-)) including loss of B lymphocyte/T lymphocyte compartmentalization, attenuation of follicular dendritic cell reticula, excessive collagen deposition, and increased high endothelial venule formation. Because TNF-alpha signaling is critical for secondary lymphoid tissue architecture, we examined compensatory changes in ADAM17 and TNF-alpha in ADAM10(B-/-) B cells. Surprisingly, defective follicular development in these mice was associated with increased rather than decreased TNF-alpha expression. In this article, we describe an increase in TNF-alpha message, mRNA stability, soluble protein release, and membrane expression in ADAM10(B-/-) B cells compared with wild type (WT), which coincides with increased ADAM17 message and protein. To assess the mechanistic contribution of excessive TNF-alpha to abnormal lymphoid architecture in ADAM10(B-/-) mice, we performed a bone marrow reconstitution study. Rectification of WT architecture was noted only in irradiated WT mice reconstituted with ADAM10(B-/-) + TNF knockout bone marrow because of normalization of TNF-alpha levels not seen in ADAM10(B-/-) alone. We conclude that ADAM17 overcompensation causes excessive TNF-alpha shedding and further upregulation of TNF-alpha expression, creating an aberrant signaling environment within B cell cortical regions of ADAM10(B-/-) lymph nodes, highlighting a key interplay between B cell ADAM10 and ADAM17 with respect to TNF alpha homeostasis. PMID- 24227780 TI - BANK1 controls CpG-induced IL-6 secretion via a p38 and MNK1/2/eIF4E translation initiation pathway. AB - BANK1, an adaptor protein expressed in B cells, plays a little understood role in B cell signaling. Because BANK1 contains an N-terminal putative Toll/IL-1R receptor domain, we used mouse Bank1(-/-) splenic B cells to test whether BANK1 affects signaling induced by the TLR9 agonist CpG. Following CpG stimulation, BANK1 deficiency reduced p38 phosphorylation without affecting that of ERK or JNK and reduced IL-6 secretion. Bank1(-/-) B cells showed reduced phosphorylation of MNK1/2 and eIF4E, suggesting an effect on translation initiation, whereas Bank1( /-) had no effect on IL-6 mRNA stability, thus suggesting that BANK1 has no effect on MK2 signaling. IL-6 secretion observed when CpG stimulation was combined with anti-CD40 was reduced in the absence of BANK1. Whereas in the presence of anti-CD40 stimulation CpG induced a stronger phosphorylation of AKT, mTOR, and 4E-BP1, Bank1(-/-) had no effect on phosphorylation of mTOR and 4E-BP1, and a weak effect on AKT, implying that BANK1 does not affect the release of eIF4E by phospho-4E-BP1. Taken together, these data establish a previously unrecognized role for BANK1 in CpG-induced responses by splenic B cells on p38 signaling and control of translation initiation of IL-6 via MNK1/2 and eIF4E. PMID- 24227781 TI - Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis. AB - The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general. PMID- 24227782 TI - Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells. AB - Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors. PMID- 24227783 TI - Cutting edge: Central memory CD8 T cells in aged mice are virtual memory cells. AB - The number of memory phenotype CD8 T cells increases dramatically with aging in both humans and mice. However, the mechanism for this is unknown. The prevailing hypothesis is that memory T cells accumulate with aging as a result of lifelong antigenic stimulation. However, data supporting this supposition are lacking. In this study, we demonstrate that central memory CD8 T cells, which represent a large majority of memory CD8 T cells in aged mice, are not memory cells that develop in response to antigenic stimulation but are virtual memory cells that develop without antigenic stimulation. In addition to phenotypic evidence, we show that accumulation of central memory CD8 T cells is independent of CD4 T cells, CCR5, and CXCR3, all of which are known to be essential for Ag-driven development of central memory CD8 T cells. Thus, this study reveals a novel mechanism for aging-related changes in CD8 T cells. PMID- 24227784 TI - The kinetics of myelin antigen uptake by myeloid cells in the central nervous system during experimental autoimmune encephalomyelitis. AB - Induction of experimental autoimmune encephalomyelitis (EAE) in susceptible animals requires reactivation of encephalitogenic CD4(+) T cells by APCs in the CNS. However, it has remained unresolved from where APCs in the CNS acquire myelin Ag for T cell activation and under which conditions, that is, whether only during EAE or also in the naive CNS. In this study, we investigated the kinetics of myelin Ag uptake by CNS APCs during EAE and in the naive CNS. Our results show that during EAE CX3CR1(+)CD11b(+) microglia were the first APCs in the CNS to contain myelin Ag upon induction of disease, albeit in very small numbers. Dendritic cells (DCs) arrived in the CNS in sizable numbers significantly later (day 5 postimmunization), without detectable myelin Ag, but acquired it by day 7 postimmunization. Furthermore, a sharp increase in neuroantigen-containing DCs coincided with the onset of EAE symptoms. Importantly, in naive mice a low but consistent number of microglia contained myelin Ag, suggesting release by oligodendrocytes under steady state conditions. Although microglia isolated from naive brain and spinal cord did not elicit a strong CD4(+) T cell response in vitro, myelin Ag-containing microglia may still play a local role in modulating encephalitogenic CD4(+) T cell responses in early EAE prior to the arrival of other professional APCs, such as DCs. Finally, newly arriving DCs in the CNS not yet loaded with myelin Ag before the onset of EAE may be a potential therapeutic target. PMID- 24227786 TI - TLR1/2 ligand-stimulated mouse liver endothelial cells secrete IL-12 and trigger CD8+ T cell immunity in vitro. AB - Liver sinusoidal endothelial cells (LSECs) are unique organ-resident APCs capable of Ag cross-presentation and subsequent tolerization of naive CD8(+) T cells. Under certain conditions, LSECs can switch from a tolerogenic to an immunogenic state and promote the development of T cell immunity. However, little is known about the mechanisms of LSECs to induce T cell immunity. In this study, we investigated whether functional maturation of LSECs can be achieved by TLR ligand stimulation and elucidated the mechanisms involved in LSEC-induced T cell immunity. We demonstrate that pretreatment of LSECs with palmitoyl-3-cysteine serine-lysine-4 (P3C; TLR1/2 ligand) but not poly(I:C) (TLR3 ligand) or LPS (TLR4 ligand) reverted their suppressive properties to induce T cell immunity. Importantly, P3C stimulation caused functional maturation of Ag-presenting LSECs and enabled them to activate virus-specific CD8(+) T cells. The LSEC-mediated CD8(+) T cell immunity was initiated by soluble mediators, one of which was IL-12 secreted at a low but sustained level after P3C stimulation. P3C stimulation did not induce programmed death ligand 1 expression on LSECs, thereby favoring T cell proliferation and activation instead of suppression. Our data suggest that LSECs undergo maturation exclusively in response to TLR1/2 ligand stimulation and that the immunological status of LSECs was dependent upon the balance between programmed death ligand 1 and IL-12 expression. These results have implications for our understanding of liver-specific tolerance and autoimmunity and for the development of strategies to overcome T cell tolerance in situations such as chronic viral liver infections or liver cancer. PMID- 24227785 TI - Cutting edge: Hypoxia-induced Nanog favors the intratumoral infiltration of regulatory T cells and macrophages via direct regulation of TGF-beta1. AB - Emerging evidence suggests a link between tumor hypoxia and immune suppression. In this study, we investigated the role of hypoxia-induced Nanog, a stemness associated transcription factor, in immune suppression. We observed that hypoxia induced Nanog correlated with the acquisition of stem cell-like properties in B16 F10 cells. We further show that Nanog was selectively induced in hypoxic areas of B16-F10 tumors. Stable short hairpin RNA-mediated depletion of Nanog, combined with melanocyte differentiation Ag tyrosinase-related protein-2 peptide-based vaccination, resulted in complete inhibition of B16-F10 tumor growth. Nanog targeting significantly reduced immunosuppressive cells (regulatory T cells and macrophages) and increased CD8(+) T effector cells in tumor bed in part by modulating TGF-beta1 production. Additionally, Nanog regulated TGF-beta1 under hypoxia by directly binding the TGF-beta1 proximal promoter. Collectively, our data establish a novel functional link between hypoxia-induced Nanog and TGF beta1 regulation and point to a major role of Nanog in hypoxia-driven immunosuppression. PMID- 24227787 TI - Transparent, flexible, superomniphobic surfaces with ultra-low contact angle hysteresis. AB - See-through surfaces: High transparency is required to use superomniphobic surfaces, which can be self-cleaning, stain-proof, anti-bio-fouling, drag reducing, or anti-fogging, for smartphone screens, eye glasses, windshields, or flat panel displays. A spray-based method has now been developed that can fabricate transparent, flexible, and highly superomniphobic surfaces. HD=hexadecane. PMID- 24227788 TI - Impaired comprehension of alternating syntactic constructions in autism. AB - Individuals on the higher-functioning end of the autism spectrum have significant impairments in communication. Language delay can occur, particularly in syntactic or structural linguistic knowledge. However, classically observed semantic deficits generally overshadow these structural deficits. This research examined the potential effects on comprehension of dative expressions that exhibited syntactic alternation versus those that were restricted, whether in syntactic construction or through marked semantic differences in construction. Children with autism and matched neurotypical control participants were presented with a sentence battery of dative statements representing these variations in construction and were asked to display basic comprehension of the sentence meaning by identifying the recipient, or indirect object, of the dative verb. Construction, restriction, and semantic differentiation variables were analyzed for potential effects on the rate of accurate comprehension. Both groups performed with greater accuracy when dative expressions used a prepositional phrase than when the dative action was expressed in the syntax. The autism group performed more poorly when the dative expression could syntactically alternate than when it was restricted. These effects improve our knowledge of how children with autism understand alternating grammatical constructions. PMID- 24227789 TI - Peptide prefractionation is essential for proteomic approaches employing multiple reaction monitoring of fruit proteomic research. AB - Off-gelTM IEF has become a popular tool in proteomics research to fractionate peptides or proteins. We conducted a detailed investigation on the fruit proteomics of apple, banana, and strawberry fruit employing Off-gelTM electrophoresis (OGE) as a crucial step to improve the proteome coverage and quantitative proteomic workflows including multiple-reaction monitoring (MRM). We provide technical details concerning the application of Off-gelTMIEF, nano-LC-MS detection, and MRM optimization and analysis. Our results demonstrated that the application of OGE is an effective method for peptide fractionation and increased significantly the number of proteins identified by at least ten times, with more total peptides detected and collected. Furthermore, we developed a protocol combining OGE and MRM studies to identify and quantitatively investigate monodehydroascorbate reductase, a key enzyme in the redox and antioxidant system of apple fruit during fruit ripening. Using this method, the quantitative changes in this protein during ripening and in response to ethylene treatment was investigated. Our results provide direct and comprehensive evidence demonstrating the benefits of OGE and its application for both shotgun and quantitative proteomics research. PMID- 24227790 TI - Unusual N-H activation of 2-aminopyrimidine: supramolecular assembly into an Ag(I) metal-organic framework. AB - A rare example of coordination at the amino group of NH2 pym (2-aminopyrimidine) relevant to N-H activation is described that leads to a novel Ag(I) -imide 3D metal-organic framework (MOF). The coordination of Ag(I) to NH2 pym produced an electron-withdrawing effect and thus increased its acidity, which facilitated the N-H activation and the subsequent formation of the Ag-imide bond. A cooperative metalation/deprotonation process for the N-H activation of NH2 pym is suggested. Interestingly, photoluminescence of 1 is switched on at the low temperature of 77 K. PMID- 24227791 TI - Is behind armour blunt trauma a real threat to users of body armour? A systematic review. AB - INTRODUCTION: Behind armour blunt trauma (BABT) has been defined as a non penetrating injury caused by the rapid deformation of body armour. There has been an increasing awareness of BABT as an injury mechanism in both the military and civilian worlds; whether BABT results in serious injuries is debatable. METHOD: A systematic review of the openly accessible literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method to investigate those injuries classified as BABT and their severity. RESULTS: 50 sources were identified that included pertinent information relevant to this systematic review on BABT injuries. Typical injuries reported included skin contusion, laceration and penetration, rib fracture and contusions to lungs, kidneys, spleen and (rarely) the heart. No evidence of fatal injuries due to BABT was identified. CONCLUSIONS: Whether BABT can lead to life-threatening injuries when small-arms ammunition impacts body armour components designed to stop that ammunition is debatable. It should be emphasised that other data may be available in government reports that are not openly available. Further research should be considered that investigates developments in body armour, including initiatives that involve reducing burden, and how they affect BABT. PMID- 24227792 TI - A chest x-ray that doesn't look right. PMID- 24227793 TI - How to use capillary refill time. PMID- 24227794 TI - Resident microbiota affect Bordetella pertussis infectious dose and host specificity. AB - Before contacting host tissues, invading pathogens directly or indirectly interact with host microbiota, but the effects of such interactions on the initial stages of infection are poorly understood. Bordetella pertussis is highly infectious among humans but requires large doses to colonize rodents, unlike a closely related zoonotic pathogen, Bordetella bronchiseptica, raising important questions about the contributions of bacterial competition to initial colonization and host selection. We observed that <100 colony-forming units (CFU) of B. bronchiseptica efficiently infected mice and displaced culturable host microbiota, whereas 10 000 CFU of B. pertussis were required to colonize murine nasal cavities and did not displace host microorganisms. Bacteria isolated from murine nasal cavities but not those from the human lower respiratory tract limited B. pertussis growth in vitro, indicating that interspecies competition may limit B. pertussis colonization of mice. Further, a broad-spectrum antibiotic treatment delivered before B. pertussis inoculation reduced the infectious dose to <100 CFU, and reintroduction of single Staphylococcus or Klebsiella species was sufficient to inhibit B. pertussis colonization of antibiotic-treated mice. Together, these results reveal that resident microorganisms can prevent B. pertussis colonization and influence host specificity, and they provide rationale for manipulating microbiomes to create more-accurate animal models of infectious diseases. PMID- 24227795 TI - Lanthanide-doped hollow nanomaterials as theranostic agents. AB - The field of theranostics has sprung up to achieve personalized medicine. The theranostics fuses diagnostic and therapeutic functions, empowering early diagnosis, targeted drug delivery, and real-time monitoring of treatment effect into one step. One particularly attractive class of nanomaterials for theranostic application is lanthanide-doped hollow nanomaterials (LDHNs). Because of the existence of lanthanide ions, LDHNs show outstanding fluorescent and paramagnetic properties, enabling them to be used as multimodal bioimaging agents. Synchronously, the huge interior cavities of LDHNs are able to be applied as efficacious tools for storage and delivery of therapeutic agents. The LDHNs can be divided into two types based on difference of component: single-phase lanthanide-doped hollow nanomaterials and lanthanide-doped hollow nanocomposites. We describe the synthesis of first kind of nanomaterials by use of hard template, soft template, template-free, and self-sacrificing template method. For lanthanide-doped hollow nanocomposites, we divide the preparation strategies into three kinds (one-step, two-step, and multistep method) according to the synthetic procedures. Furthermore, we also illustrate the potential bioapplications of these LDHNs, including biodetection, imaging (fluorescent imaging and magnetic resonance imaging), drug/gene delivery, and other therapeutic applications. PMID- 24227796 TI - Serotonin in anxiety and depression. PMID- 24227797 TI - The significance of serum total immunoglobulin E for in vitro diagnosis of allergic rhinitis. AB - BACKGROUND: Allergic rhinitis is diagnosed by clinical parameters with no widely accepted screening test. Measurement of total serum immunoglobulin E (IgE) has limited use in the general population due to a low negative predictive value. The value of total IgE level in select populations undergoing in vitro allergy testing remains unknown. The aim of this study is to determine the utility of total serum IgE in the in vitro diagnosis of allergic rhinitis. METHODS: A retrospective chart review of patients undergoing testing for allergic rhinitis was performed. Clinical parameters, total IgE level, and enzyme-linked immunosorbent assay (ELISA) for serum-specific IgE levels were analyzed with multivariate logistic regression. The positive and negative predictive values and a receiver operating characteristic (ROC) curve were used to assess the utility of total IgE in predicting serum-specific IgE test results. RESULTS: Records from 1073 patients were reviewed. ROC curve for total IgE >150 IU/mL (Sigma 0.88) indicates good discrimination in identifying patients with sensitization by in vitro testing, whereas low total IgE level had strong negative predictive value (0.87, IgE <10) in identifying negative specific IgE testing. Multivariate logistic regression showed that differences in covariables did not significantly change the odds of a positive in vitro allergy test panel. CONCLUSION: Serum total IgE level is useful in the in vitro diagnosis of allergic rhinitis. In vitro testing for specific IgE may be unnecessary in patients with low serum total IgE, whereas high total IgE level suggests that in vitro testing would confirm specific sensitizations in patients with allergic rhinitis. PMID- 24227799 TI - The effect of real-time teleconsultations between hospital-based nurses and patients with severe COPD discharged after an exacerbation. AB - We investigated the effect of daily real-time teleconsultations for one week between hospital-based nurses specialised in respiratory diseases and patients with severe COPD discharged after acute exacerbation. Patients admitted with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) at two hospitals were recruited at hospital discharge. They were randomly assigned to intervention or control. The telemedicine equipment consisted of a briefcase with built-in computer including a web camera, microphone and measurement equipment. The primary outcome was the mean number of total hospital readmissions within 26 weeks of discharge. A total of 266 patients (mean age 72 years) were allocated to either intervention (n = 132) or control (n = 134). There was no significant difference in the unconditional total mean number of hospital readmissions after 26 weeks: mean 1.4 (SD 2.1) in the intervention group and 1.6 (SD 2.4) in the control group. In a secondary analysis, there was no significant difference between the two groups in mortality, time to readmission, mean number of total hospital readmissions, mean number of readmissions with AECOPD, mean number of total hospital readmission days or mean number of readmission days with AECOPD calculated at 4, 8, 12 and 26 weeks. Thus the addition of one week of teleconsultations between hospital-based nurses and patients with severe COPD discharged after hospitalisation did not significantly reduce readmissions or affect mortality. PMID- 24227798 TI - Yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages. AB - Yersinia pestis, the bacterial agent of plague, is transmitted by fleas. The bite of an infected flea deposits Y. pestis into the dermis and triggers recruitment of innate immune cells, including phagocytic PMNs. Y. pestis can subvert this PMN response and survive at the flea-bite site, disseminate, and persist in the host. Although its genome encodes a number of antiphagocytic virulence factors, phagocytosis of Y. pestis by PMNs has been observed. This study tests the hypotheses that Y. pestis, grown at the ambient temperature of the flea vector (21 degrees C), where the major antiphagocytic virulence factors are not produced, can survive and replicate within human PMNs and can use PMNs as a route to infect macrophages subsequently. We show that Y. pestis is localized within PMN phagosomes, predominately as individual bacteria, and that intracellular bacteria can survive and replicate. Within 12 h of infection, ~70% of infected PMNs had PS on their surface and were plausibly competent for efferocytosis. With the use of live cell confocal imaging, we show that autologous HMDMs recognize and internalize infected PMNs and that Y. pestis survives and replicates within these HMDMs following efferocytosis. Addition of HMDMs to infected PMNs resulted in decreased secretion of inflammatory cytokines (compared with HMDMs incubated directly with pCD1(-) Y. pestis) and increased secretion of the anti-inflammatory cytokine IL-1ra. Thus, Y. pestis can survive and replicate within PMNs, and infected PMNs may be a route for noninflammatory infection of macrophages. PMID- 24227800 TI - Differences in the topographic profiles of retinal thickening in eyes with and without serous macular detachment associated with diabetic macular oedema. AB - PURPOSE: To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD. METHODS: Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness >350 um were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 um (W). Group means were compared between eyes with SMD and eyes without SMD. RESULTS: SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 um vs 550 um, p<0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011). CONCLUSIONS: There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO. PMID- 24227801 TI - Pazopanib eye drops: a randomised trial in neovascular age-related macular degeneration. AB - AIMS: To evaluate pazopanib eye drops in patients with subfoveal choroidal neovascularisation secondary to age-related macular degeneration. METHODS: 70 patients with minimally classic or occult subfoveal choroidal neovascularisation were randomly assigned to 5 mg/mL TID, 2 mg/mL TID, and 5 mg/mL QD pazopanib eye drops for 28 days in a multicentre, double-masked trial with an optional safety extension for up to 5 additional months. The primary outcomes were central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at Day 29. RESULTS: No significant decrease from baseline in CRT was observed overall; however, an exploratory analysis showed improvement in CRT (mean decrease of 89 MUm) in patients with the CFH TT genotype who received 5 mg/mL TID (p=0.01, n=5). Mean increases in BCVA were observed in the 5 mg/mL TID overall (4.32 letters (p=0.002, n=26)) and in those that with CFH Y402H TT (6.96 letters (p=0.02, n=5)) and CT (4.09 letters (p=0.05, n=9)) genotypes. No safety signals that precluded continued investigation were detected. CONCLUSIONS: 5 mg/mL pazopanib eye drops resulted in mean improvement in BCVA at Day 29 and improvements in vision. However, improvement in macular oedema for age-related macular degeneration was found only in the subset of subjects with the CFH Y402H TT genotype, warranting further investigation. PMID- 24227802 TI - Small incision lenticule extraction (SMILE) and femtosecond laser LASIK: comparison of corneal wound healing and inflammation. AB - AIM: To evaluate and compare early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) versus femtosecond laser laser in situ keratomileusis (LASIK). METHODS: Thirty-six eyes of 36 rabbits underwent SMILE, while another 36 eyes of 36 rabbits were treated with femtosecond laser LASIK. All the eyes were subjected to the same refractive correction of -6.00 DS/-1.00 DC. Twelve eyes that had no surgery were included for control. After euthanisation, corneal tissue sections were evaluated with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis at postoperative 4 and 24 h, immunocytochemistry for Ki67 to detect keratocyte proliferation at postoperative day 3, week 1 and month 1, and immunocytochemistry for CD11b to detect inflammation at postoperative day 1, day 3 and week 1, respectively. RESULTS: No adverse effects were noted after SMILE or LASIK. Corneal healing postoperatively was uneventful in all cases. There were significantly fewer TUNEL-positive corneal stromal cells after the SMILE procedure at 4 and 24 h postoperatively (p<0.01) compared with the LASIK procedure. In addition, immunocytochemistry showed significantly fewer Ki67-positive cells in the SMILE group than those in the femtosecond laser LASIK group at day 3 and week 1 postoperatively (p<0.05), but there was little expression of Ki67 at month 1 postoperatively in both groups. The CD11b-positive cells were significantly fewer in the SMILE group at day 1, day 3 and week 1 postoperatively (p<0.01). CONCLUSIONS: SMILE induces less keratocyte apoptosis, proliferation and inflammation compared with femtosecond laser LASIK. PMID- 24227803 TI - Validity and repeatability of the Aladdin ocular biometer. AB - AIM: To assess the accuracy and reproducibility of biometry undertaken with the Aladdin (Topcon, Tokyo, Japan) in comparison with the current gold standard device, the IOLMaster 500 (Zeiss, Jena, Germany). SETTING: University Eye Clinic, Birmingham, UK and Refractive Surgery Centre, Kiel, Germany. METHODS: The right eye of 75 patients with cataracts and 22 healthy participants were assessed using the two devices. Measurements of axial length (AL), anterior chamber depth (ACD) and keratometry (K) were undertaken with the Aladdin and IOLMaster 500 in random order by an experienced practitioner. A second practitioner then obtained measurements for each participant using the Aladdin biometer in order to assess interobserver variability. RESULTS: No statistically significant differences (p>0.05) between the two biometers were found for average difference (AL)+/-95% CI=0.01+/-0.06 mm), ACD (0.00+/-0.11 mm) or mean K values (0.08+/-0.51 D). Furthermore, interobserver variability was very good for each parameter (weighted kappa>=0.85). One patient's IOL powers could not be calculated with either biometer measurements, whereas a further three could not be analysed by the IOLMaster 500. The IOL power calculated from the valid measurements was not statistically significantly different between the biometers (p=0.842), with 91% of predictions within+/-0.25 D. CONCLUSIONS: The Aladdin is a quick, easy-to-use biometer that produces valid and reproducible results that are comparable with those obtained with the IOLMaster 500. PMID- 24227804 TI - Vascular endothelial growth factor suppression times in patients with diabetic macular oedema treated with ranibizumab. AB - BACKGROUND: To measure vascular endothelial growth factor (VEGF) levels in aqueous humour from patients with diabetic macular oedema (DME) treated with ranibizumab and to determine how long VEGF was suppressed. METHODS: In this nonrandomised, prospective clinical study, 17 eyes of 17 patients were included in the study. A total of 110 aqueous humour samples were taken before an intravitreal ranibizumab injection in patients with DME. VEGF-A was measured by Luminex multiplex bead analysis (Luminex Inc, USA). RESULTS: VEGF was completely suppressed in all patients after ranibizumab injections for a mean of 33.7 days (SD+/-5.1, range 27-42, median 34). VEGF suppression times were individually stable during the observation time of up to 16 months. There was no statistically significant difference of VEGF levels at baseline and before the beginning of a new injection series (123.6 pg/mL vs 125.1 pg/mL; p=1.0, Wilcoxon). CONCLUSIONS: Monthly ranibizumab injections lead to a complete VEGF suppression in patients with DME. The long-term stability and the range of suppression times among individuals suggest that some patients could benefit from individual injection intervals. PMID- 24227805 TI - CYP1B1 genotype influences the phenotype in primary congenital glaucoma and surgical treatment. AB - AIMS: The aim of the present work was to investigate CYP1B1 gene mutations in patients of Han Chinese ethnicity with primary congenital glaucoma (PCG), and explore the clinical characteristics associated with operative effects. METHODS: Peripheral blood genomic DNA was extracted from patients with PCG to act as a PCR template. CYP1B1 mutations were identified from the amplified coding sequences of CYP1B1. A total of 238 patients, including 116 patients described previously, were used to examine the CYP1B1 mutation frequency. Of the 238 patients, 192 patients (306 eyes) who underwent first operative treatment from January 1991 to September 2007 in the Eye, Ear, Nose & Throat Hospital of Fudan University were analysed to investigate the relationship between clinical characteristics (including CYP1B1 mutation status) and surgical effect via statistical analyses (multivariate logistic regression and Cox regression). RESULTS: The frequency of CYP1B1 mutation carriers in Chinese patients with PCG is 17.2%, and nine novel CYP1B1 mutations were discovered. The median of onset age for patients with CYP1B1 mutations (2 months) is earlier than in patients without mutations (6 months). We identified that the mutant CYP1B1 gene, as well as poorer corneal transparency, was associated with better surgical outcome. CONCLUSIONS: Patients with CYP1B1 mutations tend to have a higher operative success rate in terms of better intraocular pressure control effect. The combination of the CYP1B1 genotype (with or without mutations) and preoperative corneal opacity score can partially predict the outcome of PCG surgery. PMID- 24227806 TI - The effect of nicotine on choroidal thickness. AB - PURPOSE: To investigate the effect of nicotine on choroidal thickness using optical coherence tomography (OCT). DESIGN: Prospective, case-control study. METHODS: Sixteen young, healthy subjects and 16 age and gender matched control cases were included in this study; 4 mg nicotine gum was given to the study group and placebo gum to the control group. All participants underwent OCT scanning with a high-speed and resolution spectral-domain OCT device (3D OCT 2000, Topcon, Japan) at baseline, and 1 h following nicotine or placebo administration. The measurements were taken in the morning (10:00-12:00 hours) to avoid diurnal fluctuation. RESULTS: The median foveal choroidal thickness at baseline was 337.00 MUm (IQR 84.50), which decreased to 311.00 MUm (IQR 78.00) at 1 h following oral nicotine intake (p=0.001). The median choroidal thickness was also significantly decreased at five other extrafoveal points (p<0.05 for all). In the control group, the median baseline choroidal thickness at the fovea was 330.50 MUm (IQR 104.25), and was 332.00 MUm (IQR 103.75) at 1 h (p=0.271). CONCLUSIONS: Nicotine causes a significant decrease in choroidal thickness following oral intake. This acute decrease might be a result of reduced ocular blood flow due to the vasoconstrictive effect of nicotine. PMID- 24227807 TI - Late paravalvular abscess 6 weeks after transfemoral aortic revalving. PMID- 24227808 TI - Huge left-ventricular pseudoaneurysm compressing coronary artery 10 weeks after stabbing attack. PMID- 24227809 TI - A patient with chest pain during dobutamine stress echocardiography. PMID- 24227811 TI - Continuity of public insurance coverage: a systematic review of the literature. AB - Publicly financed insurance programs are tasked with maintaining coverage for eligible children, but published measures to assess coverage have not been evaluated. Therefore, we sought to identify and categorize measures of health insurance continuity for children and adolescents. We conducted a systematic review of Medline and HealthStar databases, review of reference lists of eligible articles, and contact with experts. We categorized measures into 8 domains based on a conceptual framework. We identified 147 measures from 84 eligible articles. Most measures evaluated the following domains: always insured (41%), repeatedly uninsured (36%), and transition out of coverage (29%), while fewer assessed single gap in coverage, always uninsured, transition into coverage, change in coverage, and eligibility. Only 18% of measures assessed associations between continuity of coverage and child and adolescent health outcomes. These results suggest that a number of measures of continuity of coverage exist, but few measures have assessed impact on outcomes. PMID- 24227810 TI - Natriuretic peptides in cardiovascular diseases: current use and perspectives. AB - The natriuretic peptides (NPs) family, including atrial, B-type, and C-type NPs, is a group of hormones possessing relevant haemodynamic and anti-remodelling actions in the cardiovascular (CV) system. Due to their diuretic, natriuretic, vasorelaxant, anti-proliferative, and anti-hypertrophic effects, they are involved in the pathogenic mechanisms leading to major CV diseases, such as heart failure (HF), coronary artery disease, hypertension and left ventricular hypertrophy, and cerebrovascular accidents. Blood levels of NPs have established predictive value in the diagnosis of HF, as well as for its prognostic stratification. In addition, they provide useful clinical information in hypertension and in both stable and unstable coronary artery disease. Structural abnormalities of atrial natriuretic peptide gene (NPPA), as well as genetically induced changes in circulating levels of NPs, have a pathogenic causal link with CV diseases and represent emerging markers of CV risk. Novel NP-based therapeutic strategies are currently under advanced clinical development, as they are expected to contribute to the future management of hypertension and HF. The present review provides a current appraisal of NPs' clinical implications and a critical perspective of the potential therapeutic impact of pharmacological manipulation of this class of CV hormones. PMID- 24227812 TI - A case study of a team-based, quality-focused compensation model for primary care providers. AB - In 2011, Fairview Health Services began replacing their fee-for-service compensation model for primary care providers (PCPs), which included an annual pay-for-performance bonus, with a team-based model designed to improve quality of care, patient experience, and (eventually) cost containment. In-depth interviews and an online survey of PCPs early after implementation of the new model suggest that it quickly changed the way many PCPs practiced. Most PCPs reported a shift in orientation toward quality of care, working more collaboratively with their colleagues and focusing on their full panel of patients. The majority reported that their quality of care had improved because of the model and that their colleagues' quality had to. The comprehensive change did, however, result in lower fee-for-service billing and reductions in PCP satisfaction. While Fairview's compensation model is still a work in progress, their early experiences can provide lessons for other delivery systems seeking to reform PCP compensation. PMID- 24227813 TI - Evaluation of a Care Coordination Measure for the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey. AB - There is widespread interest in assessing care coordination to improve overall care quality. We evaluated a five-item measure of care coordination included in the 2012 Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare survey (n = 326,194 respondents, 46% response rate). This measure includes patient reports of whether their personal doctor discusses their medicines, has medical records and other relevant information, and is informed about care from specialists, and whether the patient gets help in managing care and timely follow up on test results. A one-factor categorical confirmatory factor analytic model indicated that five items constituted a coherent scale. Estimated health-plan level reliability was 0.70 at about 102 responses per plan. The composite had a strong unique association with the CAHPS global rating of health care, controlling for the CAHPS core composite scores. This measure can be used to evaluate relative plan performance and characteristics associated with better care coordination. PMID- 24227815 TI - Evidence for upgrading the ratings for transcendental meditation: response to AHA scientific statement on alternative methods and BP. PMID- 24227816 TI - GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. AB - Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); and Emberger syndrome (primary lymphedema with MDS). A comprehensive examination of the clinical features of GATA2 deficiency is currently lacking. We reviewed the medical records of 57 patients with GATA2 deficiency evaluated at the National Institutes of Health from January 1, 1992, to March 1, 2013, and categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, pulmonary arterial hypertension 9%), dermatologic (warts 53%, panniculitis 30%), neoplastic (human papillomavirus+ tumors 35%, Epstein-Barr virus+ tumors 4%), vascular/lymphatic (venous thrombosis 25%, lymphedema 11%), sensorineural hearing loss 76%, miscarriage 33%, and hypothyroidism 14%. Viral infections and lymphedema were more common in individuals with null mutations (P = .038 and P = .006, respectively). Monocytopenia, B, NK, and CD4 lymphocytopenia correlated with the presence of disease (P < .001). GATA2 deficiency unites susceptibility to MDS/AML, immunodeficiency, pulmonary disease, and vascular/lymphatic dysfunction. Early genetic diagnosis is critical to direct clinical management, preventive care, and family screening. PMID- 24227817 TI - Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. AB - Bendamustine with bortezomib and dexamethasone was evaluated in 79 patients with relapsed/refractory multiple myeloma. Median age was 64 years, and patients had a median of 2 prior treatment lines (range, 1 to 6 lines). Bendamustine 70 mg/m(2) days 1 and 4; bortezomib 1.3 mg/m(2) intravenously days 1, 4, 8, and 11; and dexamethasone 20 mg days 1, 4, 8, and 11 once every 28 days was given for up to 8 cycles. Primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, time to response, and toxicity. ORR was 60.8%, and when minor responses were included, 75.9%. Median time to response was 31 days. ORR rate was similar in patients previously exposed to bortezomib, lenalidomide, and bortezomib plus lenalidomide. PFS was 9.7 and OS was 25.6 months. Multivariate analysis showed high lactate dehydrogenase, >=3 prior treatment lines, and low platelet counts correlating with short survival. Grade 3/4 thrombocytopenia was noted in 38%, and grade 3/4/5 infections were noted in 23%. Grade <=2 polyneuropathy increased from 19% at baseline to 52% at cycle 8 and grade 4, from 0% to 7%. Bendamustine-bortezomib-dexamethasone is active and well tolerated in patients with relapsed/refractory myeloma. This trial was registered in the EudraCT database as No. 2008-006421-13. PMID- 24227818 TI - Rational design of small molecules targeting the C2 domain of coagulation factor VIII. AB - The C domains of coagulation factors V (FV) and VIII (FVIII) are structurally conserved domains and share a common and essential function in membrane binding. In vivo regulation of thrombin formation strongly depends on the expression and regulation of the cofactor activities of FVIII and FV. With this study, we explored the possibility of inhibition of thrombin formation in full blood with small druglike molecules. Such compounds may serve as lead molecules for the development of a new type of orally available coagulation inhibitors that act by blocking the interaction between the C domains of FVIII and the membrane surface. We identified 9 novel molecules that are able to inhibit binding of the FVIII C2 domain to a model membrane by application of a combined ligand-based and target structure-based virtual screening approach that took into account the knowledge of a set of previously identified low-molecular-weight FVIII binders that were, however, not active in full blood. The half-maximal inhibitory concentration values of our newly identified compounds varied from 2.1 to 19.9 uM, of which 7 of 9 molecules did not appreciably inhibit FV membrane binding and were thus specific for FVIII. The most active bioactive compound showed activity in both plasma and in full blood. PMID- 24227819 TI - Inhibitory FcgammaRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. AB - A major feature that distinguishes type I from type II anti-CD20 monoclonal antibodies (mAbs) and reduces their therapeutic efficacy is the tendency to internalize from the cell surface. We have shown previously that the extent of internalization correlates with the capacity of type I mAb to simultaneously engage both CD20 and the inhibitory Fcgamma receptor, FcgammaRIIb, in a bipolar configuration. Here, we investigated whether mAbs directed at other B-cell surface receptors also engaged FcgammaRIIb and whether this interaction promoted internalization. Most mAbs engaged and activated FcgammaRIIb, with the strength of activation related to the level of mAb bound to the cell surface. However, engagement did not affect internalization of most mAb-ligated receptors, either in cell lines or primary chronic lymphocytic leukemia cells with the exception of CD19 and CD38. Furthermore, at high cell concentrations/density both cis and trans interactions between cell-surface bound mAb and FcgammaRIIb were evident, but trans interactions did not inhibit type I anti-CD20 mAb-mediated internalization. These data identify that FcgammaRIIb is engaged by many mAbs in both cis and trans configurations, triggering its activation, but that internalization via FcgammaRIIb occurs for only a select subset. These findings have implications when designing new antibody-based therapeutics. PMID- 24227820 TI - Crenolanib is a potent inhibitor of FLT3 with activity against resistance conferring point mutants. AB - Mutations of the type III receptor tyrosine kinase FLT3 occur in approximately 30% of acute myeloid leukemia patients and lead to constitutive activation. This has made FLT3-activating mutations an attractive drug target because they are probable driver mutations of this disease. As more potent FLT3 inhibitors are developed, a predictable development of resistance-conferring point mutations, commonly at residue D835, has been observed. Crenolanib is a highly selective and potent FLT3 tyrosine kinase inhibitor (TKI) with activity against the internal tandem duplication (FLT3/ITD) mutants and the FLT3/D835 point mutants. We tested crenolanib against a panel of D835 mutant cell lines and primary patient blasts and observed superior cytotoxic effects when compared with other available FLT3 TKIs such as quizartinib and sorafenib. Another potential advantage of crenolanib is its reduced inhibition of c-Kit compared with quizartinib. In progenitor cell assays, crenolanib was less disruptive of erythroid colony growth, which may result in relatively less myelosuppression than quizartinib. Finally, correlative data from an ongoing clinical trial demonstrate that acute myeloid leukemia patients can achieve sufficient levels of crenolanib to inhibit both FLT3/ITD and resistance-conferring FLT3/D835 mutants in vivo. Crenolanib is thus an important next-generation FLT3 TKI. PMID- 24227822 TI - Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance. AB - Patients with monoclonal gammopathy of undetermined significance (MGUS) are at increased fracture risk, and we have previously shown that MGUS patients have altered trabecular bone microarchitecture compared with controls. However, there are no data on whether the porosity of cortical bone, which may play a greater role in bone strength and the occurrence of fractures, is increased in MGUS. Thus, we studied cortical porosity and bone strength (apparent modulus) using high-resolution peripheral quantitative computed tomography imaging of the distal radius in 50 MGUS patients and 100 age-, gender-, and body mass index-matched controls. Compared with controls, MGUS patients had both significantly higher cortical porosity (+16.8%; P < .05) and lower apparent modulus (-8.9%; P < .05). Despite their larger radial bone size, MGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to controls. This increased cortical porosity may explain the increased fracture risk seen in MGUS patients. PMID- 24227824 TI - PET/MRI: a new technology in the field of molecular imaging. AB - BACKGROUND: The introduction of the new simultaneous PET/MRI scanner opens new opportunities in functional imaging. SOURCES OF DATA: This article is based on the literature review and our personal experience of the first simultaneous PET/MRI scanner in the UK. AREAS OF AGREEMENT: PET/CT is well established and a key component of management guidance in a range of diseases. MRI has superior soft tissue resolution, which is useful in the evaluation of many diseases. AREAS OF CONTROVERSY: There are currently no guidelines regarding clinical use of PET/MRI, and those centres with a PET/MRI facility are undertaking research to look for a 'key application'. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: This review briefly describes some of the technical advances, present comparisons with the diagnostic performance of current imaging modalities (PET/CT and MRI) and identifies potential indications and research directions. PMID- 24227825 TI - NHS 111 led to more ambulance dispatches, finds study. PMID- 24227821 TI - Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. AB - This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged >=12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week. PMID- 24227827 TI - Secondary prevention for patients after a myocardial infarction: summary of updated NICE guidance. PMID- 24227828 TI - Cleared GP asks police to investigate patient for perverting course of justice. PMID- 24227829 TI - Sailing without a lookout: cuts to the Office for National Statistics. PMID- 24227830 TI - Transverse ultrasound image through the orbit. PMID- 24227831 TI - Evidence is lacking for or against multivitamins to prevent heart disease or cancer, US task force says. PMID- 24227832 TI - GP who married widower shortly after patient's death is suspended for six months. PMID- 24227834 TI - Equine tetherin blocks retrovirus release and its activity is antagonized by equine infectious anemia virus envelope protein. AB - Human tetherin is a host restriction factor that inhibits replication of enveloped viruses by blocking viral release. Tetherin has an unusual topology that includes an N-terminal cytoplasmic tail, a single transmembrane domain, an extracellular domain, and a C-terminal glycosylphosphatidylinositol anchor. Tetherin is not well conserved across species, so it inhibits viral replication in a species-specific manner. Thus, studies of tetherin activities from different species provide an important tool for understanding its antiviral mechanism. Here, we report cloning of equine tetherin and characterization of its antiviral activity. Equine tetherin shares 53%, 40%, 36%, and 34% amino acid sequence identity with feline, human, simian, and murine tetherins, respectively. Like the feline tetherin, equine tetherin has a shorter N-terminal domain than human tetherin. Equine tetherin is localized on the cell surface and strongly blocks human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and equine infectious anemia virus (EIAV) release from virus-producing cells. The antiviral activity of equine tetherin is neutralized by EIAV envelope protein, but not by the HIV-1 accessory protein Vpu, which is a human tetherin antagonist, and EIAV envelope protein does not counteract human tetherin. These results shed new light on our understanding of the species-specific tetherin antiviral mechanism. PMID- 24227835 TI - Evolution and diversity in human herpes simplex virus genomes. AB - Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. PMID- 24227836 TI - Histone deacetylase classes I and II regulate Kaposi's sarcoma-associated herpesvirus reactivation. AB - In primary effusion lymphoma (PEL) cells infected with latent Kaposi's sarcoma associated herpesvirus (KSHV), the promoter of the viral lytic switch gene, Rta, is organized into bivalent chromatin, similar to cellular developmental switch genes. Histone deacetylase (HDAC) inhibitors (HDACis) reactivate latent KSHV and dramatically remodel the viral genome topology and chromatin architecture. However, reactivation is not uniform across a population of infected cells. We sought to identify an HDACi cocktail that would uniformly reactivate KSHV and reveal the regulatory HDACs. Using HDACis with various specificities, we found that class I HDACis were sufficient to reactivate the virus but differed in potency. Valproic acid (VPA) was the most effective HDACi, inducing lytic cycle gene expression in 75% of cells, while trichostatin A (TSA) induced less widespread lytic gene expression and inhibited VPA-stimulated reactivation. VPA was only slightly superior to TSA in inducing histone acetylation of Rta's promoter, but only VPA induced significant production of infectious virus, suggesting that HDAC regulation after Rta expression has a dramatic effect on reactivation progression. Ectopic HDACs 1, 3, and 6 inhibited TPA-stimulated KSHV reactivation. Surprisingly, ectopic HDACs 1 and 6 stimulated reactivation independently, suggesting that the stoichiometries of HDAC complexes are critical for the switch. Tubacin, a specific inhibitor of the ubiquitin-binding, proautophagic HDAC6, also inhibited VPA-stimulated reactivation. Immunofluorescence indicated that HDAC6 is expressed diffusely throughout latently infected cells, but its expression level and nuclear localization is increased during reactivation. Overall, our data suggest that inhibition of HDAC classes I and IIa and maintenance of HDAC6 (IIb) activity are required for optimal KSHV reactivation. PMID- 24227838 TI - Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41. AB - Induction of broadly neutralizing antibodies (bNAbs) is an important goal for HIV 1 vaccine development. Two autoreactive bNAbs, 2F5 and 4E10, recognize a conserved region on the HIV-1 envelope glycoprotein gp41 adjacent to the viral membrane known as the membrane-proximal external region (MPER). They block viral infection by targeting a fusion-intermediate conformation of gp41, assisted by an additional interaction with the viral membrane. Another MPER-specific antibody, 10E8, has recently been reported to neutralize HIV-1 with potency and breadth much greater than those of 2F5 or 4E10, but it appeared not to bind phospholipids and might target the untriggered envelope spikes, raising the hope that the MPER could be harnessed for vaccine design without major immunological concerns. Here, we show by three independent approaches that 10E8 indeed binds lipid bilayers through two hydrophobic residues in its CDR H3 (third heavy-chain complementarity determining region). Its weak affinity for membranes in general and preference for cholesterol-rich membranes may account for its great neutralization potency, as it is less likely than other MPER-specific antibodies to bind cellular membranes nonspecifically. 10E8 binds with high affinity to a construct mimicking the fusion intermediate of gp41 but fails to recognize the envelope trimers representing the untriggered conformation. Moreover, we can improve the potency of 4E10 without affecting its binding to gp41 by a modification of its lipid interacting CDR H3. These results reveal a general mechanism of HIV-1 neutralization by MPER-specific antibodies that involves interactions with viral lipids. PMID- 24227837 TI - Novel neuroprotective GSK-3beta inhibitor restricts Tat-mediated HIV-1 replication. AB - The implementation of new antiretroviral therapies targeting transcription of early viral proteins in postintegrated HIV-1 can aid in overcoming current therapy limitations. Using high-throughput screening assays, we have previously described a novel Tat-dependent HIV-1 transcriptional inhibitor named 6 bromoindirubin-3'-oxime (6BIO). The screening of 6BIO derivatives yielded unique compounds that show potent inhibition of HIV-1 transcription. We have identified a second-generation derivative called 18BIOder as an inhibitor of HIV-1 Tat dependent transcription in TZM-bl cells and a potent inhibitor of GSK-3beta kinase in vitro. Structurally, 18BIOder is half the molecular weight and structure of its parental compound, 6BIO. More importantly, we also have found a different GSK-3beta complex present only in HIV-1-infected cells. 18BIOder preferentially inhibits this novel kinase complex from infected cells at nanomolar concentrations. Finally, we observed that neuronal cultures treated with Tat protein are protected from Tat-mediated cytotoxicity when treated with 18BIOder. Overall, our data suggest that HIV-1 Tat-dependent transcription is sensitive to small-molecule inhibition of GSK-3beta. PMID- 24227839 TI - Retrovirus-specific differences in matrix and nucleocapsid protein-nucleic acid interactions: implications for genomic RNA packaging. AB - Retroviral RNA encapsidation involves a recognition event between genomic RNA (gRNA) and one or more domains in Gag. In HIV-1, the nucleocapsid (NC) domain is involved in gRNA packaging and displays robust nucleic acid (NA) binding and chaperone functions. In comparison, NC of human T-cell leukemia virus type 1 (HTLV-1), a deltaretrovirus, displays weaker NA binding and chaperone activity. Mutation of conserved charged residues in the deltaretrovirus bovine leukemia virus (BLV) matrix (MA) and NC domains affects virus replication and gRNA packaging efficiency. Based on these observations, we hypothesized that the MA domain may generally contribute to NA binding and genome encapsidation in deltaretroviruses. Here, we examined the interaction between HTLV-2 and HIV-1 MA proteins and various NAs in vitro. HTLV-2 MA displays higher NA binding affinity and better chaperone activity than HIV-1 MA. HTLV-2 MA also binds NAs with higher affinity than HTLV-2 NC and displays more robust chaperone function. Mutation of two basic residues in HTLV-2 MA alpha-helix II, previously implicated in BLV gRNA packaging, reduces NA binding affinity. HTLV-2 MA binds with high affinity and specificity to RNA derived from the putative packaging signal of HTLV-2 relative to nonspecific NA. Furthermore, an HIV-1 MA triple mutant designed to mimic the basic character of HTLV-2 MA alpha-helix II dramatically improves binding affinity and chaperone activity of HIV-1 MA in vitro and restores RNA packaging to a DeltaNC HIV-1 variant in cell-based assays. Taken together, these results are consistent with a role for deltaretrovirus MA proteins in viral RNA packaging. PMID- 24227841 TI - Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8. AB - RNA-specific adenosine deaminase (ADAR)-mediated adenosine-to-inosine (A-to-I) editing is a critical arm of the antiviral response. However, mechanistic insights into how A-to-I RNA editing affects viral infection are lacking. We posited that inosine incorporation into RNA facilitates sensing of nonself RNA by innate immune sensors and accordingly investigated the impact of inosine-modified RNA on Toll-like receptor 7 and 8 (TLR7/8) sensing. Inosine incorporation into synthetic single-stranded RNA (ssRNA) potentiated tumor necrosis factor alpha (TNF-alpha) or alpha interferon (IFN-alpha) production in human peripheral blood mononuclear cells (PBMCs) in a sequence-dependent manner, indicative of TLR7/8 recruitment. The effect of inosine incorporation on TLR7/8 sensing was restricted to immunostimulatory ssRNAs and was not seen with inosine-containing short double stranded RNAs or with a deoxy-inosine-modified ssRNA. Inosine-mediated increase of self-secondary structure of an ssRNA resulted in potentiated IFN-alpha production in human PBMCs through TLR7 recruitment, as established through the use of a TLR7 antagonist and Tlr7-deficient cells. There was a correlation between hyperediting of influenza A viral ssRNA and its ability to stimulate TNF alpha, independent of 5'-triphosphate residues, and involving Adar-1. Furthermore, A-to-I editing of viral ssRNA directly enhanced mouse Tlr7 sensing, when present in proportions reproducing biologically relevant levels of RNA editing. Thus, we demonstrate for the first time that inosine incorporation into immunostimulatory ssRNA can potentiate TLR7/8 activation. Our results suggest a novel function of A-to-I RNA editing, which is to facilitate TLR7/8 sensing of phagocytosed viral RNA. PMID- 24227840 TI - Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface. AB - The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study, we identify the cellular chromosome receptor for IE1. We demonstrate that the viral protein targets human nucleosomes by directly binding to core histones in a nucleic acid-independent manner. IE1 exhibits two separable histone interacting regions with differential binding specificities for H2A-H2B and H3 H4. The H2A-H2B binding region was mapped to an evolutionarily conserved 10-amino acid motif within the chromatin-tethering domain (CTD) of IE1. Results from experimental approaches combined with molecular modeling indicate that the IE1 CTD adopts a beta-hairpin structure, docking with the acidic pocket formed by H2A H2B on the nucleosome surface. IE1 binds to the acidic pocket in a way similar to that of the latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma associated herpesvirus. Consequently, the IE1 and LANA CTDs compete for binding to nucleosome cores and chromatin. Our work elucidates in detail how a key viral regulator is anchored to human chromosomes and identifies the nucleosomal acidic pocket as a joint target of proteins from distantly related viruses. Based on the striking similarities between the IE1 and LANA CTDs and the fact that nucleosome targeting by IE1 is dispensable for productive replication even in "clinical" strains of hCMV, we speculate that the two viral proteins may serve analogous functions during latency of their respective viruses. PMID- 24227842 TI - APOBEC3 deaminases induce hypermutation in human papillomavirus 16 DNA upon beta interferon stimulation. AB - Apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3) proteins are interferon (IFN)-inducible antiviral factors that counteract various viruses such as hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) by inducing cytidine (C)-to-uracil (U) mutations in viral DNA and inhibiting reverse transcription. However, whether APOBEC3 proteins (A3s) can hypermutate human papillomavirus (HPV) viral DNA and exhibit antiviral activity in human keratinocyte remains unknown. Here we examined the involvement of A3s in the HPV life cycle using cervical keratinocyte W12 cells, which are derived from low grade lesions and retain episomal HPV16 genomes in their nuclei. We focused on the viral E2 gene as a potential target for A3-mediated hypermutation because this gene is frequently found as a boundary sequence in integrated viral DNA. Treatment of W12 cells with beta interferon (IFN-beta) increased expression levels of A3s such as A3A, A3F, and A3G and induced C-to-U conversions in the E2 gene in a manner depending on inhibition of uracil DNA glycosylase. Exogenous expression of A3A and A3G also induced E2 hypermutation in W12 cells. IFN-beta induced hypermutation was blocked by transfection of small interfering RNAs against A3G (and modestly by those against A3A). However, the HPV16 episome level was not affected by overexpression of A3A and A3G in W12 cells. This study demonstrates that endogenous A3s upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes, and a pathogenic consequence of E2 hypermutation is discussed. PMID- 24227843 TI - TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. AB - The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-CoV S protein (SARS-S) activation has not been determined. Here, we show that arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for cleavage by TMPRSS2 and HAT and that ACE2 processing is required for augmentation of SARS-S-driven entry by these proteases. In contrast, ACE2 cleavage was dispensable for activation of the viral S protein. Expression of TMPRSS2 increased cellular uptake of soluble SARS-S, suggesting that protease dependent augmentation of viral entry might be due to increased uptake of virions into target cells. Finally, TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry. Collectively, our results in conjunction with those of previous studies indicate that TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion. These observations have interesting implications for the development of novel therapeutics. In addition, they should spur efforts to determine whether receptor cleavage promotes entry of other coronaviruses, which use peptidases as entry receptors. PMID- 24227844 TI - Discovery of a novel bottlenose dolphin coronavirus reveals a distinct species of marine mammal coronavirus in Gammacoronavirus. AB - While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (Tursiops aduncus), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22 positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 * 10(3) to 1 * 10(5) copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (Ks) to the number of nonsynonymous substitutions per nonsynonymous site (Ka) in multiple regions of the genome, especially the S gene (Ka/Ks ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species, Cetacean coronavirus, in Gammacoronavirus, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species, Avian coronavirus, in Gammacoronavirus. PMID- 24227845 TI - A cell-biased effect of estrogen in prion infection. AB - Prion disorders are associated with the accumulation of a misfolded form (PrP(Sc)) of the normal prion protein, PrP(C). Here, we show that estrogen acts as a regulator of the processes of both prion infection and prion maintenance. Estrogen was found to be cell biased in its effect; it protected cells against prion infection in a prevention mode and enabled prion maintenance in a treatment mode. These processes were regulated by the estrogen receptor subtypes Eralpha and Erbeta. By using specific receptor agonists, Eralpha was found to be the main receptor active in slowing prion infection, whereas in chronically infected cells, although Eralpha allowed partial maintenance of PrP(Sc) levels, Erbeta was the main receptor involved in maintaining PrP(Sc) in a treatment paradigm. A cell biased effect of estrogen has been reported for other neurodegenerative disorders, including Alzheimer's disease. Estrogen's effect is dependent on the cell's health status, which impacts the use of estrogen. This work also identified that by targeting the estrogen receptors with the selective estrogen receptor modulators tamoxifen (Tam) and 4-hydroxy-tamoxifen (OHT), PrP(Sc) could be cleared from prion-infected cell culture. Tam and OHT had half-maximal inhibitory concentrations for clearance of PrP(Sc) of 0.47 MUM and 0.14 nM, respectively. This work identifies further factors involved in the prion disease process, and through antagonism of the estrogen system, we demonstrate that the estrogen system is a target for controlling PrP(Sc) levels. PMID- 24227846 TI - Immunoprevalence and immunodominance of HLA-Cw*0801-restricted T cell response targeting the hepatitis B virus envelope transmembrane region. AB - HLA-C-restricted T cells have been shown to play an important role in HIV control, but their impact on protection or pathogenesis in other viral infections remains elusive. Here, we characterized the hierarchy of HLA class I-restricted hepatitis B virus (HBV) epitopes targeted by CD8 T cells in HBV-infected subjects. The frequency of CD8 T cells specific for a panel of 18 HBV epitopes (restricted by HLA-A*0201/03/07 [hereinafter HLA-A0201/03/07], -A1101, -A2402/07, -B5801, -B4001, -B1301, and -Cw0801) was quantified in a total of 59 subjects who resolved HBV infection. We found that the HLA-Cw0801-restricted epitope comprised of Env residues 171 to 180 (Env171-180) is immunoprevalent in the Southeast Asian subjects (10/17 HLA-Cw0801-positive subjects) and immunodominant in the majority of HLA-Cw0801-positive subjects able to control HBV infection. HLA-Cw0801 restricted Env171-180-specific CD8 T cells recognized endogenously produced HBV surface antigen (HBsAg) and tolerated amino acid variations within the epitope detected in HBV genotypes B and C. In conclusion, we demonstrate that the HLA Cw0801-restricted Env171-180 T cell response is an important component of the HBV specific adaptive T cell immunity in Asians infected with HBV. Thus, HLA-C restricted T cells might play an important role in various viral infections. PMID- 24227847 TI - Processing of the l1 52/55k protein by the adenovirus protease: a new substrate and new insights into virion maturation. AB - Late in adenovirus assembly, the viral protease (AVP) becomes activated and cleaves multiple copies of three capsid and three core proteins. Proteolytic maturation is an absolute requirement to render the viral particle infectious. We show here that the L1 52/55k protein, which is present in empty capsids but not in mature virions and is required for genome packaging, is the seventh substrate for AVP. A new estimate on its copy number indicates that there are about 50 molecules of the L1 52/55k protein in the immature virus particle. Using a quasi in vivo situation, i.e., the addition of recombinant AVP to mildly disrupted immature virus particles, we show that cleavage of L1 52/55k is DNA dependent, as is the cleavage of the other viral precursor proteins, and occurs at multiple sites, many not conforming to AVP consensus cleavage sites. Proteolytic processing of L1 52/55k disrupts its interactions with other capsid and core proteins, providing a mechanism for its removal during viral maturation. Our results support a model in which the role of L1 52/55k protein during assembly consists in tethering the viral core to the icosahedral shell and in which maturation proceeds simultaneously with packaging, before the viral particle is sealed. PMID- 24227848 TI - Risk assessment of H2N2 influenza viruses from the avian reservoir. AB - H2N2 influenza A viruses were the cause of the 1957-1958 pandemic. Historical evidence demonstrates they arose from avian virus ancestors, and while the H2N2 subtype has disappeared from humans, it persists in wild and domestic birds. Reemergence of H2N2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. Thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterization, and antiviral testing. The data presented here are a risk assessment of 22 avian H2N2 viruses isolated from wild and domestic birds over 6 decades. Our data show that they have a low rate of genetic and antigenic evolution and remained similar to isolates circulating near the time of the pandemic. Most isolates replicated in mice and human bronchial epithelial cells, but replication in swine tissues was low or absent. Multiple isolates replicated in ferrets, and 3 viruses were transmitted to direct-contact cage mates. Markers of mammalian adaptation in hemagglutinin (HA) and PB2 proteins were absent from all isolates, and they retained a preference for avian-like alpha2,3-linked sialic acid receptors. Most isolates remained antigenically similar to pandemic A/Singapore/1/57 (H2N2) virus, suggesting they could be controlled by the pandemic vaccine candidate. All viruses were susceptible to neuraminidase inhibitors and adamantanes. Nonetheless, the sustained pathogenicity of avian H2N2 viruses in multiple mammalian models elevates their risk potential for human infections and stresses the need for continual surveillance as a component of prepandemic planning. PMID- 24227849 TI - Expression profile of microRNAs in Epstein-Barr virus-infected AGS gastric carcinoma cells. AB - Latent infection with Epstein-Barr virus (EBV) is responsible for multiple types of malignancies, including 10% of all gastric carcinomas. The microRNA (miRNA) expression in several EBV-infected AGS gastric carcinoma cell lines was determined. Infected cells expressed the viral BamHI A rightward transcript (BART) miRNAs at high levels and had consistently decreased expression of a small fraction of cellular miRNAs with specific downregulation of tumor suppressor miRNAs. These changes likely reflect expression of the viral noncoding RNAs and not latent protein expression. PMID- 24227850 TI - Virus-viroid interactions: Citrus Tristeza Virus enhances the accumulation of Citrus Dwarfing Viroid in Mexican lime via virus-encoded silencing suppressors. AB - An assay to identify interactions between Citrus Dwarfing Viroid (CDVd) and Citrus Tristeza Virus (CTV) showed that viroid titer was enhanced by the coinfecting CTV in Mexican lime but not in etrog citron. Since CTV encodes three RNA silencing suppressors (RSSs), p23, p20 and p25, an assay using transgenic Mexican limes expressing each RSS revealed that p23 and, to a lesser extent, p25 recapitulated the effect observed with coinfections of CTV and CDVd. PMID- 24227851 TI - Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication. AB - A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV specific T-cell responses targeting conserved regions and induction of HIV specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of virus replication to recognize all clade B Gag sequence variants encoded by at least 5% of the sequences in the Los Alamos National Laboratory HIV database (1,300 peptides) using gamma interferon and interleukin-2 (IFN-gamma/IL-2) FluoroSpot analysis. While targeting of conserved regions was similar in the two groups (P = 0.47), we found that subjects with control of virus replication demonstrated marginally lower recognition of Gag epitope variants than subjects with normal progression (P = 0.05). In viremic controllers and progressors, we found variant recognition to be associated with viral load (r = 0.62, P = 0.001). Interestingly, we show that increased overall sequence coverage, defined as the overall proportion of HIV database sequences targeted through the Gag-specific repertoire, is inversely associated with viral load (r = -0.38, P = 0.03). Furthermore, we found that sequence coverage, but not variant recognition, correlated with increased recognition of a panel of clade B HIV founder viruses (r = 0.50, P = 0.004). We propose sequence coverage by HIV Gag specific immune responses as a possible correlate of protection that may contribute to control of virus replication. Additionally, sequence coverage serves as a valuable measure by which to evaluate the protective potential of future vaccination strategies. PMID- 24227852 TI - Characterization of the noncoding regions of the 1918 influenza A H1N1 virus. AB - The terminal noncoding region (NCR) sequences of the eight gene segments of the influenza A/Brevig Mission/1/1918 (H1N1) virus were determined by rapid amplification of cDNA ends (RACE). Chimeric viruses encoding the open reading frames of the 1918 virus but flanked by either the wild-type 1918 NCR sequences or the NCR sequences of two other H1N1 virus strains, A/WSN/1933 and A/New York/312/2001, were produced. No growth differences between the NCR variant 1918 influenza viruses were noted. PMID- 24227853 TI - Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag. AB - CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses. To be active, CD40L must cluster CD40 receptors on responding cells. To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct. With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex. This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro. Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus. The importance of the multitrimeric nature of the complex was shown using a plasmid lacking the N terminus of SPD that produced a single trimer fusion protein. This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge. An adenovirus 5 (Ad5) vaccine incorporating SPD-Gag CD40L was much stronger than Ad5 expressing Gag alone (Ad5-Gag) and induced complete protection (i.e., sterilizing immunity) from vaccinia-Gag challenge. Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses. PMID- 24227854 TI - Wheat streak mosaic virus infects systemically despite extensive coat protein deletions: identification of virion assembly and cell-to-cell movement determinants. AB - Viral coat proteins function in virion assembly and virus biology in a tightly coordinated manner with a role for virtually every amino acid. In this study, we demonstrated that the coat protein (CP) of Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) is unusually tolerant of extensive deletions, with continued virion assembly and/or systemic infection found after extensive deletions are made. A series of deletion and point mutations was created in the CP cistron of wild-type and/or green fluorescent protein-tagged WSMV, and the effects of these mutations on cell-to-cell and systemic transport and virion assembly of WSMV were examined. Mutants with overlapping deletions comprising N terminal amino acids 6 to 27, 36 to 84, 85 to 100, 48 to 100, and 36 to 100 or the C-terminal 14 or 17 amino acids systemically infected wheat with different efficiencies. However, mutation of conserved amino acids in the core domain, which may be involved in a salt bridge, abolished virion assembly and cell-to cell movement. N-terminal amino acids 6 to 27 and 85 to 100 are required for efficient virion assembly and cell-to-cell movement, while the C-terminal 65 amino acids are dispensable for virion assembly but are required for cell-to-cell movement, suggesting that the C terminus of CP functions as a dedicated cell-to cell movement determinant. In contrast, amino acids 36 to 84 are expendable, with their deletion causing no obvious effects on systemic infection or virion assembly. In total, 152 amino acids (amino acids 6 to 27 and 36 to 100 and the 65 amino acids at the C-terminal end) of 349 amino acids of CP are dispensable for systemic infection and/or virion assembly, which is rare for multifunctional viral CPs. PMID- 24227855 TI - Evolution of bovine ephemeral fever virus in the Australian episystem. AB - Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that causes a debilitating disease of cattle in Africa, Asia, and Australia; however, its global geodynamics are poorly understood. An evolutionary analysis of G gene (envelope glycoprotein) ectodomain sequences of 97 BEFV isolates collected from Australia during 1956 to 2012 revealed that all have a single common ancestor and are phylogenetically distinct from BEFV sampled in other geographical regions. The age of the Australian clade is estimated to be between 56 and 65 years, suggesting that BEFV has entered the continent on few occasions since it was first reported in 1936 and that the 1955-1956 epizootic was the source of all currently circulating viruses. Notably, the Australian clade has evolved as a single genetic lineage across the continent and at a high evolutionary rate of ~10(-3) nucleotide substitutions/site/year. Screening of 66 isolates using monoclonal antibodies indicated that neutralizing antigenic sites G1, G2, and G4 have been relatively stable, although variations in site G3a/b defined four antigenic subtypes. A shift in an epitope at site G3a, which occurred in the mid 1970s, was strongly associated with a K218R substitution. Similarly, a shift at site G3b was associated primarily with substitutions at residues 215, 220, and 223, which map to the tip of the spike on the prefusion form of the G protein. Finally, we propose that positive selection on residue 215 was due to cross reacting neutralizing antibody to Kimberley virus (KIMV). This is the first study of the evolution of BEFV in Australia, showing that the virus has entered the continent only once during the past 50 to 60 years, it is evolving at a relatively constant rate as a single genetic lineage, and although the virus is relatively stable antigenically, mutations have resulted in four antigenic subtypes. Furthermore, the study shows that the evolution of BEFV in Australia appears to be driven, at least in part, by cross-reactive antibodies to KIMV which has a similar distribution and ecology but has not been associated with disease. As BEFV and KIMV are each known to be present in Africa and Asia, this interaction may occur on a broader geographic scale. PMID- 24227856 TI - Inhibition of Bim enhances replication of varicella-zoster virus and delays plaque formation in virus-infected cells. AB - Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID- 24227857 TI - Differential impact of magnitude, polyfunctional capacity, and specificity of HIV specific CD8+ T cell responses on HIV set point. AB - Defining the characteristics of HIV-specific CD8(+) T cell responses that lead to viral control is crucial for vaccine development. We evaluated the differential impact of magnitude, polyfunctional capacity, and specificity of the CD8(+) response at approximately 6 months postinfection on the viral set point at 12 months in a cohort of HIV-infected individuals. High frequencies of Gag and Nef responses endowed with four functions were the best predictors of a low viral set point. PMID- 24227860 TI - Elimination of friend retrovirus in the absence of CD8+ T cells. PMID- 24227861 TI - A novel strategy to develop a robust infectious hepatitis C virus cell culture system directly from a clinical isolate. AB - Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases. Progress in the HCV field was greatly enhanced by constructing infectious cDNA clone of JFH-1. Since then, JFH-1-based intra- and intergenotypic recombinants have been developed, and this permitted the study of vaccines and antiviral inhibitors for all genotypes. Recently, highly efficient HCV culture systems have been established by using consensus sequence-based clones. We developed a novel strategy to construct infectious HCV cDNA clone by combining functional screening of sequences directly from a genotype 2a clinical isolate (PR63) and cell culture adaptation. Using JFH-1 cDNA as the starting backbone, we sequentially replaced the JFH-1 fragments with a sequence from the pools of PR63 sequences. Through engineering adaptive mutations that improve HCV infectivity, we finally established a full-length cell culture-derived infectious clone of PR63, named PR63cc, that could efficiently produce virus particles in Huh7-derived cells, with peak titers of 1.6 * 10(5) focus-forming units/ml. The PR63cc could be neutralized by an anti-E2 antibody and inhibited by antiviral agents but appeared more resistant to an NS5A inhibitor than JFH-1. In summary, we developed a new approach to construct an infectious HCV cDNA clone that can produce viruses efficiently in cell culture. This approach could be applied to other viral isolates, with potential implications for individualized treatments of HCV patients. PMID- 24227862 TI - The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. AB - Clinical resistance to rilpivirine (RPV), a novel nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI), is associated an E-to-K mutation at position 138 (E138K) in RT together with an M184I/V mutation that confers resistance against emtricitabine (FTC), a nucleoside RT inhibitor (NRTI) that is given together with RPV in therapy. These two mutations can compensate for each other in regard to fitness deficits conferred by each mutation alone, raising the question of why E138K did not arise spontaneously in the clinic following lamivudine (3TC) use, which also selects for the M184I/V mutations. In this context, we have investigated the role of a N348I connection domain mutation that is prevalent in treatment-experienced patients. N348I confers resistance to both the NRTI zidovudine (ZDV) and the NNRTI nevirapine (NVP) and was also found to be associated with M184V and to compensate for deficits associated with the latter mutation. Now, we show that both N348I alone and N348I/M184V can prevent or delay the emergence of E138K under pressure with RPV or a related NNRTI, termed etravirine (ETR). N348I also enhanced levels of resistance conferred by E138K against RPV and ETR by 2.2- and 2.3-fold, respectively. The presence of the N348I or M184V/N348I mutation decreased the replication capacity of E138K virus, and biochemical assays confirmed that N348I, in a background of E138K, impaired RT catalytic efficiency and RNase H activity. These findings help to explain the low viral replication capacity of viruses containing the E138K/N348I mutations and how N348I delayed or prevented the emergence of E138K in patients with M184V containing viruses. PMID- 24227865 TI - Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming. AB - Hepatitis B virus replicates a DNA genome through reverse transcription of a pregenomic RNA (pgRNA) by using a multifunctional polymerase (HP). A critical function of HP is its specific association with a viral RNA signal, termed epsilon (Hepsilon), located on pgRNA, which is required for specific packaging of pgRNA into viral nucleocapsids and initiation of viral reverse transcription. HP initiates reverse transcription by using itself as a protein primer (protein priming) and Hepsilon as the obligatory template. HP is made up of four domains, including the terminal protein (TP), the spacer, the reverse transcriptase (RT), and the RNase H domains. A recently developed, Hepsilon-dependent, in vitro protein priming assay was used in this study to demonstrate that almost the entire TP and RT domains and most of the RNase H domain were required for protein priming. Specific residues within TP, RT, and the spacer were identified as being critical for HP-Hepsilon binding and/or protein priming. Comparison of HP sequence requirements for Hepsilon binding, pgRNA packaging, and protein priming allowed the classification of the HP mutants into five groups, each with distinct effects on these complex and related processes. Detailed characterization of HP requirements for these related and essential functions of HP will further elucidate the mechanisms of its multiple functions and aid in the targeting of these functions for antiviral therapy. PMID- 24227863 TI - Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus. AB - Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. Mutations in the surface spike (S) protein of human respiratory coronavirus OC43 appear after persistent infection of human cells of the central nervous system, a possible viral adaptation to this environment. Furthermore, a single amino acid change in the viral S protein modulated virus-induced neuropathology in mice from an encephalitis to a neuropathology characterized by flaccid paralysis, which involves glutamate excitotoxicity. We now show that memantine, a drug that is used for alleviating symptoms associated with neuropathology, such as Alzheimer's disease, can partially restore the physiological state of infected mice by limiting both neurodegeneration and viral replication. This suggests that memantine could be used as an antiviral agent while improving neurological symptoms in various neurological diseases with a viral involvement. PMID- 24227866 TI - EBP1, a novel host factor involved in primer binding site-dependent restriction of moloney murine leukemia virus in embryonic cells. AB - Mouse embryonic cells are unable to support the replication of Moloney murine leukemia virus (MLV). The integrated viral DNA is transcriptionally silenced, largely due to binding of host transcriptional repressors to the primer binding site (PBS) of the provirus. We have previously shown that a PBS DNA-binding repressor complex contains ZFP809 and TRIM28. Here, we identified ErbB3-binding protein 1 (EBP1) to be a novel component of the ZFP809-TRIM28 silencing complex and show that EBP1 depletion reduces PBS-mediated retroviral silencing. PMID- 24227868 TI - Children's exposure to second-hand smoke at home in Bangladesh: a community survey. AB - OBJECTIVES: In Bangladesh, second-hand smoke (SHS) is recognised as a principal source of indoor air pollution and a major public health problem. However, we know little about the extent to which people are aware of the risks of second hand smoking, or restrict smoking indoors or in the presence of children. We report findings of a community survey exploring these questions. DESIGN AND SETTING: A total of 722 households were surveyed in urban and rural settings, using a multistage cluster random sampling approach and a semistructured questionnaire. In addition, we used qualitative methods to further explore the determinants of smoking-related behaviours inside homes. FINDINGS: 55% of households in our sample had at least one regular smoker. Smoking indoors was common. In 30% of households, smoking occurred in the presence of children, exposing nearly 40% of children to SHS. Overall, we found a lack of awareness about the harms associated with second-hand smoking. CONCLUSIONS: Our study highlights that a sizeable proportion of children and non-smokers are exposed to SHS at homes in Bangladesh, posing a significant and grave public health problem. In the absence of any impetus to legislate against smoking in private places, an educational approach is recommended to change smoking practices at home. Such a shift toward voluntary smoking restrictions at home would require behaviour change among smokers and support from non-smoking family members. PMID- 24227867 TI - Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model. AB - The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation. PMID- 24227869 TI - Are familial factors underlying the association between socioeconomic position and prescription medicine? A register-based study on Danish twins. AB - OBJECTIVES: Although well established, the association between socioeconomic position and health and health behaviour is not clearly understood, and it has been speculated that familial factors, for example, dispositional factors or exposures in the rearing environment, may be underlying the association. The objective was to compare prescription fillings within twin pairs who are partly or fully genetically identical and share childhood exposures. DESIGN: Twin cohort study. SETTING: Denmark. PARTICIPANTS: Data from the Danish Twin Registry were linked to registers in Statistics Denmark and the Danish Registry of Medicinal Product statistics. A total of 8582 monozygotic (MZ) and 15 788 dizygotic same sex (DZSS) twins were included. OUTCOME MEASURES: Number of prescription fillings during follow-up (1995-2005) was analysed according to education and income. Results of unpaired and intrapair analyses were compared. RESULTS: An inverse social gradient in filling of prescriptions for all-purpose and system-specific drugs was observed in the unpaired analyses. In the intrapair analyses, associations were attenuated some in DZSS and more in MZ twins. Filling of drugs targeting the nervous system was still strongly associated with income in the intrapair analyses. CONCLUSIONS: Familial factors seem to account for part of the observed social inequality in filling of prescription medicine. PMID- 24227870 TI - Intention-to-treat analyses and missing data approaches in pharmacotherapy trials for alcohol use disorders. AB - OBJECTIVES: Intention to treat (ITT) is an analytic strategy for reducing potential bias in treatment effects arising from missing data in randomised controlled trials (RCTs). Currently, no universally accepted definition of ITT exists, although many researchers consider it to require either no attrition or a strategy to handle missing data. Using the reports of a large pool of RCTs, we examined discrepancies between the types of analyses that alcohol pharmacotherapy researchers stated they used versus those they actually used. We also examined the linkage between analytic strategy (ie, ITT or not) and how missing data on outcomes were handled (if at all), and whether data analytic and missing data strategies have changed over time. DESIGN: Descriptive statistics were generated for reported and actual data analytic strategy and for missing data strategy. In addition, generalised linear models determined changes over time in the use of ITT analyses and missing data strategies. PARTICIPANTS: 165 RCTs of pharmacotherapy for alcohol use disorders. RESULTS: Of the 165 studies, 74 reported using an ITT strategy. However, less than 40% of the studies actually conducted ITT according to the rigorous definition above. Whereas no change in the use of ITT analyses over time was found, censored (last follow-up completed) and imputed missing data strategies have increased over time, while analyses of data only for the sample actually followed have decreased. CONCLUSIONS: Discrepancies in reporting versus actually conducting ITT analyses were found in this body of RCTs. Lack of clarity regarding the missing data strategy used was common. Consensus on a definition of ITT is important for an adequate understanding of research findings. Clearer reporting standards for analyses and the handling of missing data in pharmacotherapy trials and other intervention studies are needed. PMID- 24227871 TI - Feasibility, acceptability and outcomes at a 12-month follow-up of a novel community-based intervention to prevent type 2 diabetes in adults at high risk: mixed methods pilot study. AB - OBJECTIVES AND DESIGN: Lifestyle interventions can prevent type 2 diabetes (T2D) in adults with impaired glucose tolerance. In a mixed methods pilot study, we aimed to assess the feasibility, acceptability and outcomes at a 12-month follow up of a behavioural intervention for adults at risk of T2D. PARTICIPANTS: Adults aged 45-65 years with a Finnish Diabetes Risk Score (FINDRISC) >=11. SETTING: The intervention was delivered in leisure and community settings in a local authority that ranks in the 10 most socioeconomically deprived in England. INTERVENTION: A 10-week supported programme to promote increased physical activity (PA), healthy eating and weight loss was delivered by fitness trainers as twice-weekly group PA or cookery sessions, each followed by behavioural counselling with support to 12 months. OUTCOME MEASURES: We assessed feasibility and acceptability of the intervention, and change in behavioural and health-related outcomes at 6 and 12 months. RESULTS: From 367 registers of interest, 218 participants were recruited to the programme with baseline mean (SD): age 53.6 (6) years, FINDRISC 13.9 (3.1), body mass index 33.5 (5.9) kg/m(2), waist circumference 108.1 (13.7) cm, PA levels (self-report): daily total 49.1 (5.9) metabolic-equivalent (MET) h/day. Follow-up at 12 months was completed by 134 (61%) participants, with an estimated mean (95% CI) change from baseline in weight -5.7 (-7.8 to -2.8); -2.8 (-3.8 to 1.9) kg, waist circumference -7.2 (-9.2 to -5.2); -6.0 (-7.1 to -5.0) cm, and PA level 7.9 (5.8 to 10.1); 6.7 (5.2 to 8.2) MET h/day equivalent, for men and women, respectively (from covariance pattern mixed models). Participants reported an enjoyable, sociable and supportive intervention experience. CONCLUSIONS: Participants' views indicated a high level of intervention acceptability. High retention and positive outcomes at 12 months provide encouraging indications of the feasibility and potential effectiveness of the intervention. A definitive trial of this intervention is warranted. PMID- 24227872 TI - Long-term prediction of major coronary or ischaemic stroke event in a low incidence Southern European population: model development and evaluation of clinical utility. AB - OBJECTIVE: To develop a long-term prediction model of first major cardiovascular event and to assess its clinical utility in a low-incidence European population. SETTING: Four independent population-based cohorts enrolled between 1986 and 1993 in Northern Italy. PARTICIPANTS AND METHODS: N=5247 35-year-old to 69-year-old men and women free of cardiovascular disease at baseline. Absolute 20-year risk of first fatal or non-fatal coronary or ischaemic stroke event (monitoring trends and determinants in cardiovascular disease (MONICA) validated) was estimated from gender-specific Cox models. MAIN OUTCOME MEASURES: Model discrimination (area under the receiver operating characteristic (ROC)-curve, AUC). 'High-risk' subjects were identified based on several threshold values for the 20-year predicted risk. Clinical utility was defined in terms of fraction of missed events (events among those considered at low-risk) and unnecessary treatment (false:true positive ratio). A net benefit curve was also provided. RESULTS: Kaplan-Meier 20-year risk was 16.1% in men (315 events) and 6.1% in women (123 events). Model discrimination (AUC=0.737 in men, 0.801 in women) did not change significantly as compared to 10-year prediction time interval. In men, with respect to risk stratification based on the number of risk factors, a 20% predicted risk cut-off would miss less events (36% vs 50%) and reduce unnecessary treatment (false:true positive ratio 2.2 vs 3.0); the net benefit was higher over the whole range of threshold values. Similar considerations hold for women. CONCLUSIONS: Long-term prediction has good discrimination ability and is clinically useful for risk stratification in primary prevention. A clinical utility analysis is recommended to identify the optimal stratification according to different public health goals. PMID- 24227873 TI - Active buildings: modelling physical activity and movement in office buildings. An observational study protocol. AB - INTRODUCTION: Health benefits of regular participation in physical activity are well documented but population levels are low. Office layout, and in particular the number and location of office building destinations (eg, print and meeting rooms), may influence both walking time and characteristics of sitting time. No research to date has focused on the role that the layout of the indoor office environment plays in facilitating or inhibiting step counts and characteristics of sitting time. The primary aim of this study was to investigate associations between office layout and physical activity, as well as sitting time using objective measures. METHODS AND ANALYSIS: Active buildings is a unique collaboration between public health, built environment and computer science researchers. The study involves objective monitoring complemented by a larger questionnaire arm. UK office buildings will be selected based on a variety of features, including office floor area and number of occupants. Questionnaires will include items on standard demographics, well-being, physical activity behaviour and putative socioecological correlates of workplace physical activity. Based on survey responses, approximately 30 participants will be recruited from each building into the objective monitoring arm. Participants will wear accelerometers (to monitor physical activity and sitting inside and outside the office) and a novel tracking device will be placed in the office (to record participant location) for five consecutive days. Data will be analysed using regression analyses, as well as novel agent-based modelling techniques. ETHICS AND DISSEMINATION: The results of this study will be disseminated through peer reviewed publications and scientific presentations. Ethical approval was obtained through the University College London Research Ethics Committee (Reference number 4400/001). PMID- 24227874 TI - Power and its applications: a new module in the medical curriculum at Trinity College Dublin. PMID- 24227875 TI - A short history of providing medical history within the British medical undergraduate curriculum. AB - This article aims to discuss the history of medical history in the British medical undergraduate curriculum and it reviews the main characters and organisations that have attempted to earn it a place in the curriculum. It also reviews the arguments for and against the study of the subject that have been used over the last 160 years. PMID- 24227876 TI - Diagnosis of neuroschistosomiasis by antibody specificity index and semi quantitative real-time PCR from cerebrospinal fluid and serum. AB - We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia and paraesthesia without pareses. A serum-cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy. PMID- 24227877 TI - Clinical utility of loop-mediated isothermal amplification for rapid diagnosis of Mycoplasma pneumoniae in children. AB - Loop-mediated isothermal amplification (LAMP) is a cost-effective and rapid method for identifying Mycoplasma pneumoniae (MP). We investigated the utility of the LAMP assay in diagnosing MP pneumonia among children in a clinical setting. In this prospective study, the cause of community-acquired pneumonia was evaluated in 111 patients for whom MP was the suspected pathogen. All participants were patients at a city hospital in Japan between April 2012 and September 2012. Throat swabs for the LAMP assay were obtained at admission, and paired serum samples to measure antibody titres to MP by particle agglutination were obtained at admission and during convalescence. Overall, 45 of 111 (41 %) patients had a fourfold or greater increase in MP titres and received a diagnosis of MP pneumonia. Among them, 43 (96 %) patients (median age, 9 years) were positive on the LAMP assay and had a fourfold or greater increase in MP titres. The median interval from fever onset to collection of throat swabs was 7 days (range, 4-10 days). As compared with paired serum titres, the LAMP assay enabled quicker diagnosis of MP (median interval, 13 vs. 7 days), thereby allowing early initiation of appropriate antimicrobial therapy. PMID- 24227878 TI - Prospective evaluation of the VITEK MS for the routine identification of bacteria and yeast in the clinical microbiology laboratory: assessment of accuracy of identification and turnaround time. AB - This study assessed the accuracy of bacterial and yeast identification using the VITEK MS, and the time to reporting of isolates before and after its implementation in routine clinical practice. Three hundred and sixty-two isolates of bacteria and yeast, consisting of a variety of clinical isolates and American Type Culture Collection strains, were tested. Results were compared with reference identifications from the VITEK 2 system and with 16S rRNA sequence analysis. The VITEK MS provided an acceptable identification to species level for 283 (78 %) isolates. Considering organisms for which genus-level identification is acceptable for routine clinical care, 315 isolates (87 %) had an acceptable identification. Six isolates (2 %) were identified incorrectly, five of which were Shigella species. Finally, the time for reporting the identifications was decreased significantly after implementation of the VITEK MS for a total mean reduction in time of 10.52 h (P<0.0001). Overall, accuracy of the VITEK MS was comparable or superior to that from the VITEK 2. The findings were also comparable to other studies examining the accuracy of the VITEK MS, although differences exist, depending on the diversity of species represented as well as on the versions of the databases used. The VITEK MS can be incorporated effectively into routine use in a clinical microbiology laboratory and future expansion of the database should provide improved accuracy for the identification of micro-organisms. PMID- 24227881 TI - Reconstruction with a patient-specific titanium implant after a wide anterior chest wall resection. AB - The reconstruction of full-thickness chest wall defects is a challenging problem for thoracic surgeons, particularly after a wide resection of the chest wall that includes the sternum. The location and the size of the defect play a major role when selecting the method of reconstruction, while acceptable cosmetic and functional results remain the primary goal. Improvements in preoperative imaging techniques and reconstruction materials have an important role when planning and performing a wide chest wall resection with a low morbidity rate. In this report, we describe the reconstruction of a wide anterior chest wall defect with a patient-specific custom-made titanium implant. An infected mammary tumour recurrence in a 62-year old female, located at the anterior chest wall including the sternum, was resected, followed by a large custom-made titanium implant. Latissimus dorsi flap and split-thickness graft were also used for covering the implant successfully. A titanium custom-made chest wall implant could be a viable alternative for patients who had large chest wall tumours. PMID- 24227882 TI - Computed tomography surveillance scanning after lung cancer surgery: mathematical optimization of scanning interval based on tumour biology. AB - OBJECTIVES: To determine the optimal computed tomography (CT) scanning interval for the detection of a new primary lung cancer and recurrent disease, utilizing the known mathematical formula for tumour doubling. METHODS: where: Ti interval time, Di initial diameter and Do final diameter. Three doubling times were utilized for demonstration of the principle, 30, 80 and 100 days. RESULTS: A worst-case scenario for a doubling time of 30 days indicates that a 2-mm tumour will need 210 days (7 months) to reach 10 mm in diameter and 300 days (10 months) to reach 20 mm in diameter. Over a 5-year (60 months) follow-up period, this indicates that eight CT scans will be required if a threshold of 10 mm is desired or six if a threshold of 20 mm is desired. For an 80-day doubling time over a 5 year (60 months) follow-up period, three CT scans will be required if a threshold of 10 mm is desired or two if a threshold of 20 mm is desired and for a 100-day doubling time. Assuming complete histological clearance of the primary lung cancer and that recurrence occurs from a microscopic focus, a time period of 1700 days (56 months) is required to reach 10 mm in diameter. CONCLUSIONS: The exact timing of interval CT scanning to detect recurrence and new primary tumour depends on philosophy; however, three monthly CT scanning is probably inappropriate, and scanning every 7 months is probably the shortest interval that is clinically useful, particularly for small-cell lung cancer in the first year after treatment. We recommend, based on mathematical modelling, a scanning interval post-potentially curative resection surgery for primary lung cancer of 18 months, which is different from the current guidelines on surveillance, for non-small-cell lung cancer. PMID- 24227883 TI - Centrosome-dependent asymmetric inheritance of the midbody ring in Drosophila germline stem cell division. AB - Many stem cells, including Drosophila germline stem cells (GSCs), divide asymmetrically, producing one stem cell and one differentiating daughter. Cytokinesis is often asymmetric, in that only one daughter cell inherits the midbody ring (MR) upon completion of abscission even in apparently symmetrically dividing cells. However, whether the asymmetry in cytokinesis correlates with cell fate or has functional relevance has been poorly explored. Here we show that the MR is asymmetrically segregated during GSC divisions in a centrosome age dependent manner: male GSCs, which inherit the mother centrosome, exclude the MR, whereas female GSCs, which we here show inherit the daughter centrosome, inherit the MR. We further show that stem cell identity correlates with the mode of MR inheritance. Together our data suggest that the MR does not inherently dictate stem cell identity, although its stereotypical inheritance is under the control of stemness and potentially provides a platform for asymmetric segregation of certain factors. PMID- 24227884 TI - Isoform-specific tethering links the Golgi ribbon to maintain compartmentalization. AB - Homotypic membrane tethering by the Golgi reassembly and stacking proteins (GRASPs) is required for the lateral linkage of mammalian Golgi ministacks into a ribbon-like membrane network. Although GRASP65 and GRASP55 are specifically localized to cis and medial/trans cisternae, respectively, it is unknown whether each GRASP mediates cisternae-specific tethering and whether such specificity is necessary for Golgi compartmentalization. Here each GRASP was tagged with KillerRed (KR), expressed in HeLa cells, and inhibited by 1-min exposure to light. Significantly, inactivation of either GRASP unlinked the Golgi ribbon, and the immediate effect of GRASP65-KR inactivation was a loss of cis- rather than trans-Golgi integrity, whereas inactivation of GRASP55-KR first affected the trans- and not the cis-Golgi. Thus each GRASP appears to play a direct and cisternae-specific role in linking ministacks into a continuous membrane network. To test the consequence of loss of cisternae-specific tethering, we generated Golgi membranes with a single GRASP on all cisternae. Remarkably, the membranes exhibited the full connectivity of wild-type Golgi ribbons but were decompartmentalized and defective in glycan processing. Thus the GRASP isoforms specifically link analogous cisternae to ensure Golgi compartmentalization and proper processing. PMID- 24227885 TI - Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure. AB - Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule associated proteins (MAPs) or motors. Acetylation of Lys-40 on alpha-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo-electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, alphaTAT1, with microtubules and find that alphaTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of alphaTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments. PMID- 24227886 TI - Processive acceleration of actin barbed-end assembly by N-WASP. AB - Neuronal Wiskott-Aldrich syndrome protein (N-WASP)-activated actin polymerization drives extension of invadopodia and podosomes into the basement layer. In addition to activating Arp2/3, N-WASP binds actin-filament barbed ends, and both N-WASP and barbed ends are tightly clustered in these invasive structures. We use nanofibers coated with N-WASP WWCA domains as model cell surfaces and single actin-filament imaging to determine how clustered N-WASP affects Arp2/3 independent barbed-end assembly. Individual barbed ends captured by WWCA domains grow at or below their diffusion-limited assembly rate. At high filament densities, however, overlapping filaments form buckles between their nanofiber tethers and myosin attachment points. These buckles grew ~3.4-fold faster than the diffusion-limited rate of unattached barbed ends. N-WASP constructs with and without the native polyproline (PP) region show similar rate enhancements in the absence of profilin, but profilin slows barbed-end acceleration from constructs containing the PP region. Increasing Mg(2+) to enhance filament bundling increases the frequency of filament buckle formation, consistent with a requirement of accelerated assembly on barbed-end bundling. We propose that this novel N-WASP assembly activity provides an Arp2/3-independent force that drives nascent filament bundles into the basement layer during cell invasion. PMID- 24227887 TI - ARP2/3-mediated junction-associated lamellipodia control VE-cadherin-based cell junction dynamics and maintain monolayer integrity. AB - Maintenance and remodeling of endothelial cell junctions critically depend on the VE-cadherin/catenin complex and its interaction with the actin filament cytoskeleton. Here we demonstrate that local lack of vascular endothelial (VE) cadherin at established cell junctions causes actin-driven and actin-related protein 2/3 complex (ARP2/3)-controlled lamellipodia to appear intermittently at those sites. Lamellipodia overlap the VE-cadherin-free adjacent plasma membranes and facilitate formation of new VE-cadherin adhesion sites, which quickly move into the junctions, driving VE-cadherin dynamics and remodeling. Inhibition of the ARP2/3 complex by expression of the N-WASP (V)CA domain or application of two ARP2/3 inhibitors, CK-548 and CK-666, blocks VE-cadherin dynamics and causes intercellular gaps. Furthermore, expression of carboxy-terminal-truncated VE cadherin increases the number of ARP2/3-controlled lamellipodia, whereas overexpression of wild-type VE-cadherin largely blocks it and decreases cell motility. The data demonstrate a functional interrelationship between VE-cadherin mediated cell adhesion and actin-driven, ARP2/3-controlled formation of new VE cadherin adhesion sites via intermittently appearing lamellipodia at established cell junctions. This coordinated mechanism controls VE-cadherin dynamics and cell motility and maintains monolayer integrity, thus potentially being relevant in disease and angiogenesis. PMID- 24227889 TI - Protein-tyrosine phosphatase H1 increases breast cancer sensitivity to antiestrogens by dephosphorylating estrogen receptor at Tyr537. AB - Estrogen receptor alpha (ERalpha or ER) is the only target of breast cancer therapy using antiestrogens. However, about 50% of ER-expressing breast cancer is intrinsically refractory to the antihormone therapy and strategies to improve the therapeutic response are urgently needed. Dynamic ER phosphorylation and dephosphorylation play an important role in ER activity and antihormone response. Although more than 10 kinases participate in phosphorylating ER protein, phosphatases involved remain mostly unidentified. Here, we tested the hypothesis that the protein-tyrosine phosphatase H1 (PTPH1) may regulate ER tyrosine phosphorylation and thereby impact breast cancer antihormone sensitivity. Our results showed that PTPH1 dephosphorylates ER at Tyr537 in vitro and in breast cancer cells. Moreover, PTPH1 stimulates ER nuclear accumulation and increases breast cancer sensitivity to tamoxifen (TAM) and/or fulvestrant in cell culture and in a xenograft model. Further analysis revealed that PTPH1 depends on its catalytic activity to stimulate ER nuclear accumulation and to enhance breast cancer antihormone sensitivity. These studies thus identified PTPH1 as a novel ER phosphatase and further demonstrate a therapeutic potential of enhancing breast cancer sensitivity to antiestrogens through dephosphorylating ER by PTPH1. PMID- 24227890 TI - Superior antitumor activity of a novel bispecific antibody cotargeting human epidermal growth factor receptor 2 and type I insulin-like growth factor receptor. AB - The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2) positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin-like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell resistance to trastuzumab therapy. Previously, we reported that the anti-IGF IR mAb m590 inhibits proliferation and migration of breast cancer MCF-7 cells in vitro. Here, we generated a "knobs-into-holes" bispecific antibody (Bi-Ab) against HER2 and IGF-IR by engineering trastuzumab and m590. We compared the effects of Bi-Ab treatment in vitro and in SKOV-3 HER2- and IGF-IR-overexpressing cancer xenograft mouse model with those of m590 and trastuzumab treatment alone or in combination. Bi-Ab effectively inhibited proliferation of HER2- and IGF-IR overexpressing ovarian cancer SKOV-3 cells in vitro by ablating receptor phosphorylation and downstream PI3K/Akt and mitogen-activated protein kinase signaling. Bi-Ab more effectively inhibited cancer growth in SKOV-3 HER2- and IGF IR-overexpressing cancer xenograft mouse model than m590 and trastuzumab alone or in combination. Mice bearing SKOV-3 HER2- and IGF-IR-overexpressing xenografts showed extensive and sustainable tumor regression when treated with Bi-Ab. Our results suggest that Bi-Ab has superior antitumor activity compared with monospecific antibodies, and cotargeting HER2 and IGF-IR may be clinically beneficial in minimizing the acquired resistance to trastuzumab therapy. PMID- 24227888 TI - ESCRT regulates surface expression of the Kir2.1 potassium channel. AB - Protein quality control (PQC) is required to ensure cellular health. PQC is recognized for targeting the destruction of defective polypeptides, whereas regulated protein degradation mechanisms modulate the concentration of specific proteins in concert with physiological demands. For example, ion channel levels are physiologically regulated within tight limits, but a system-wide approach to define which degradative systems are involved is lacking. We focus on the Kir2.1 potassium channel because altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels. Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum-associated degradation (ERAD). Next a synthetic gene array identifies nonessential genes that negatively regulate Kir2.1. The most prominent gene family that emerges from this effort encodes members of endosomal sorting complex required for transport (ESCRT). ERAD and ESCRT also mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role. Thus multiple proteolytic pathways control Kir2.1 levels at the plasma membrane. PMID- 24227891 TI - A1180V of cardiac sodium channel gene (SCN5A): is it a risk factor for dilated cardiomyopathy or just a common variant in Han Chinese? AB - Our previous study of a Chinese family with dilated cardiomyopathy (DCM) suggested that A1180V of the cardiac sodium channel gene (SCN5A) was associated with the disease within this family. According to data deposited in dbSNP, however, A1180V has been found in some small samples of the Asian population. In this study, we followed up the affected pedigree and expanded the investigation of the prevalence of A1180V in 460 unrelated healthy Han Chinese. Besides, we searched and analyzed it in other database as well. During the follow-up period, 1 A1180V carrier's condition deteriorated a lot, and another 4 carriers progressed to DCM or atrioventricular block (AVB). We also found that the A1180V was absent among the 460 individuals (0%, 0/460), and the carrier frequency of A1180V among Chinese was about 0.51% obtained from the 1000 genome project. In conclusion, our finding suggests that A1180V is a potential risk factor for DCM, and it is extremely rare among Healthy Han Chinese. PMID- 24227892 TI - Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness. AB - Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean +/- sd, range) rose significantly (P < 0.001) from 68 +/- 14 (60-102) at 1300 m to 183 +/- 107 (65-519); 143 +/- 66 (60-315) and 150 +/- 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 +/- 34 versus 171 +/- 19 versus 124 +/- 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS. PMID- 24227893 TI - Local and systemic inflammatory responses to experimentally induced gingivitis. AB - This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF alpha decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-alpha during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual. PMID- 24227894 TI - Surgical treatment of hypopharyngeal cancer: a review of the literature and proposal for a decisional flow-chart. AB - Surgical resection is one of the standard therapeutic choices for the treatment of hypopharyngeal cancer, whether or not combined with postoperative radiotherapy. The type of operation depends on the extension of the lesion and the subsites involved and often requires some form of reconstruction. Reconstructive strategies depend on whether the larynx, or part of it, has been preserved. We believe that the decisional flow-chart of the reconstructive methods after hypopharyngeal cancer resection should be based not only on the extent of resection, but also on the subsites involved. This report presents a literature review on the management of cancer of the hypopharynx and a proposal for a surgical decisional flow-chart. PMID- 24227895 TI - Vascular pedicle ossification of free fibular flap: is it a rare phenomenon? Is it possible to avoid this risk? AB - Free fibula flap is the most common free tissue transfer for maxillary and mandibular reconstructions. The distal part of the harvested bone is transferred, while the proximal part is removed by sub-periosteum dissection. The vascularized periosteum attached to the vascular pedicle has osteogenic potential. 61 patients reconstructed with free fibula flaps were divided in 2 groups: 41 flaps performed with a standard technique and 20 flaps performed by dissecting the periosteum from the pedicle. Patients were followed up with orthopantomography and CT scan at 6, 12, 18 and 24 months after surgery. The minimum follow-up time was 18 months. With retrospective analysis of the first group we diagnosed 7 pedicle ossifications on 41 reconstructions (17%). In the second group, no pedicle ossification was observed (p < 0.05). The dissection of periosteum from the vascular pedicle of free fibula flaps avoids the risk of ossification. PMID- 24227896 TI - Is there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable? A survey of head and neck surgical/radiation oncologists. AB - Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (ROs) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of ROs recommended PRT in the case of positive/close margins (R(+)/R(close)) or in the case of initial involvement of thyroid cartilage (pT3(tci)). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in R(close) and with 56-60 Gy (34%) in pT3(tci). In Conclusion, OPL raises new considerations about PRT. PMID- 24227897 TI - The rs39335 polymorphism of the RELN gene is not associated with otosclerosis in a southern Italian population. AB - Otosclerosis, the single most common cause of hearing impairment in white adults, is characterised by bone dystrophy localized to the otic capsule and isolated endochondral bone sclerosis with alternating phases of bone resorption and formation. Conductive hearing loss develops when otosclerotic foci invade the stapedio-vestibular joint (oval window) and interfere with free motion of the stapes, but affected subjects frequently develop profound sensorineural hearing loss. The aetiology of otosclerosis is unknown. In the last years, several association studies have been performed and have suggested that single nucleotide polymorphisms in some genes may be implicated in development of otosclerosis. The strongest association has been demonstrated for the reelin gene, located on chromosome 7q22.1, which encodes an extracellular matrix protein. The involvement of reelin in the pathogenesis of otosclerosis is controversial; it was identified in European and North African populations, but was excluded in an Indian population. To analyze the role of reelin in otosclerosis, it has been studied in a case-control analysis for the polymorphism rs39335 in a southern Italy population. In this population, the pathogenic link between the rs39335 variant and otosclerosis was excluded. PMID- 24227898 TI - Posterior lacrimal sac approach technique without stenting in endoscopic dacryocystorhinostomy. AB - The purpose of this study is to evaluate the effectiveness of endoscopic dacryocystorhinostomy by the posterior lacrimal sac approach without use of lacrimal stents or harvest of mucosal flaps as a valid surgical procedure for the treatment of an obstruction of the lacrimal pathways. A retrospective evaluation was conducted in a cohort of 75 patients between 2007 and 2011. A total of 78 endoscopic dacryocystorhinostomies were analyzed in 75 patients. After a mean follow-up of 25.7 months (minimum 12 months), 93.3% had a complete relief of symptoms after surgery. Our experience appears to confirm that the endoscopic posterior lacrimal sac approach with no stent insertion or mucosal flaps creation is a good alternative to other known endoscopic procedures. PMID- 24227899 TI - Evaluation of hearing aid benefit through a new questionnaire: CISQ (Complete Intelligibility Spatiality Quality). AB - The purpose of this work was to create a rapid and simple instrument to evaluate the benefits of a hearing aid, that was at the same time reliable and complete. We created a new questionnaire by integration of other well consolidated psychometric tests to better investigate all the aspects that contribute in determining the hearing aid benefit, also considering as important some areas that are not usually considered (spatiality and quality of sound). We started from a 36-item questionnaire divided in six subscales (spatiality and quality of signal, intelligibility in silence, background noise intelligibility, averseness and reverberation), and submitted it to patients before hearing aid application and at 2-3 months after that. A statistically significant difference between results before and after hearing aid application was found. To obtain the final 30-item questionnaire, we analyzed the reliability of each subscale using Cronbach's alpha coefficient, and eliminated the item whose internal consistency was lower for every subscale. For these reasons, the CISQ questionnaire is a rapid and simple test that can be considered a reliable and complete instrument to evaluate the benefits of a hearing aid. PMID- 24227900 TI - The impact of a multidisciplinary approach on response rate of mandibular advancing device therapy in patients with obstructive sleep apnoea syndrome. AB - The aim of the present study was to evaluate the importance of a multidisciplinary approach on increasing the response ratio expectation to mandibular advancing device (MAD) therapy in patients with obstructive sleep apnoea syndrome, especially in severe cases. Forty-two mild-to-severe OSAS patients were selected, after comprehensive evaluation by neurologists, otorhinolaryngologists and orthodontists, and treated with a Somnodent(r) device. Six months later, a polysomnographic exam with the MAD in situ was performed. The paired t-test evaluated the effectiveness of therapy and the results were compared with data from systematic reviews. The average treatment response was statistically significant for the apnoea/hypopnea index (AHI) and oxygen desaturation index and was higher than the outcomes presented in literature. An optimum therapy response (AHI < 5) was observed in 53% of patients (40% in severe OSAS) and a good response (AHI < 10) in 73% of patients (50% in severe OSAS). The Somnodent(r) device was effective and the multidisciplinary patient selection improved the response ratio compared to that reported by previous systematic reviews. PMID- 24227901 TI - Ectopic lingual goiter treated by transoral robotic surgery. AB - Multinodular goiter in lingual thyroid is quite rare. Surgical removal is indicated in symptomatic patients and when cancer is suspected. An external approach is most often used, but is associated with morbidity and sequelae. In this study, we present for the first time the technique of transoral robotic surgery (TORS) for removal of a massive lingual goiter. Prospective patient data were collected, including demographics, medical history, symptoms, comorbidities and drugs prescribed. The da Vinci Surgical System was used for a transoral approach to the oropharynx. The technique was validated in a 31-year-old woman with signs and symptoms of multinodular goiter presenting since childhood. The procedure required 115 min, with intervals as follows: tracheotomy, 25 min; robot setting time, 20 min; and console time, 70 min. TOR S is feasible in cases of multinodular goiter in a lingual thyroid. The procedure appears to be safe, with quick recovery of swallowing and speech. PMID- 24227902 TI - Sudden clinical course of an unusual ENT tumour: clinical pictures of extramedullary plasmacytoma secondary to multiple myeloma. AB - Extramedullary plasmacytoma (EMP) is a rare monoclonal plasmacytic proliferation involving upper airways in 80% of cases. The heterogeneous pattern of frequency in the head and neck area may result in insidious clinical expressions that are potentially lethal for the patient. The presentation and management of two suggestive clinical photographs characterized by sudden and aggressive EMP development secondary to multiple myeloma are discussed. PMID- 24227903 TI - Intramuscular haemangioma of the levator anguli oris: a rare case. AB - Intramuscular haemangiomas are benign malformations of blood vessels occurring in skeletal muscles. Because of the rarity of these lesions, their deep location and variable clinical presentation, they often pose diagnostic difficulties. We herein present the first reported case of intramuscular haemangioma occurring in the levator anguli oris muscle. A 26-year-old man was referred to our Department for evaluation and management of a progressive swelling of the right cheek. Based mainly on the imaging findings, a preoperative diagnosis of intramuscular haemangioma was made and surgery was performed. During intervention, a highly vascular soft tissue mass was identified within the levator anguli oris muscle. The lesion was completely removed via an intraoral approach, and histopathological examination showed an intramuscular haemangioma. PMID- 24227904 TI - Palliative combined treatment for unresectable cutaneous basosquamous cell carcinoma of the head and neck. AB - A case is presented of a patient with a skin basosquamous cell carcinoma of the frontal region infiltrating the cerebral tissue and with a widespread unresectable regional metastatic ulceration of the left parotid region. The patient underwent combined palliative treatment: surgical coverage of the ulceration by means of a pectoralis mayor flap transposition and radiotherapy. After 18 months of follow-up, no signs of tumour progression were noted, the patient is currently free from pain, no increase in trismus was seen, and a slight gain in weight was recorded. Unresectable cancer is mainly treated by concurrent chemoradiation; radiotherapy, however, is contraindicated in deep neoplastic ulcerations with exposure of large vessels. The data reported suggest that surgical coverage of an unresectable neoplastic ulcer is feasible, and combined with early administration of radiation permits a palliative approach in an otherwise untreatable condition. PMID- 24227905 TI - The discovery of stapes. AB - Giovanni Filippo Ingrassia revisited and redefined some of Galeno's reports, and was recognized as one of the leading Italian Physicians of the 16th century. Ingrassia principally studied the skull, and gave very important contributions to otorhinolaryngology, including the discovery of the stapes. He also isolated the inferior nasal concha from the maxillary bone, described the frontal sinus, the pterygopalatine fossa and several foramina of the skull. Ingrassia firstly attributed a sensorial function to the middle ear bones, which he called fifth particular function. He also added some details to the description of the VIII cranial nerve, which introduces the concept of bone conducting sound. The most important discovery in Ingrassia's study about the hearing organ was the first description of the third bone of the ossicular chain that he called "stapes". Ingrassia should thus be reconsidered under a new light for his important discovery and for his intuitions about the stapes and its role in hearing. It is appropriate for a Sicilian physician to be placed at his rightful place side-by side with Eustachio and Valsalva in the history of otology. PMID- 24227906 TI - P600-like positivity and Left Anterior Negativity responses are elicited by semantic reversibility in nonanomalous sentences. AB - ERPs are commonly elicited by semantic and syntactic violations in sentences, leading to proposals that they reflect neural activity underlying ordinary language comprehension. We examined ERPs in an auditory sentence-picture-matching task, using nonanomalous sentences that were either semantically reversible, (boy pushes girl) or irreversible, (boy eats apple). Timelocked to the end of the critical clause, which occurred in the middle of a longer sentence, we observed an enhanced central-posterior positivity in response to the reversible sentences. The topography of this response is consistent with the P600 potential reported in studies of syntactic anomalies and other manipulations related to sentence structure. Following the end of the sentence, during a memory delay period prior to picture onset, reversible sentences also evoked a protracted anterior negativity, predominantly on the left. This negativity was stronger for sentences containing relative clauses compared to simple active sentences, but did not differ between object-embedded and the less complex subject-embedded clauses. The observation of a P600 occurring selectively in reversible sentences supports the interpretation of that potential as reflecting the syntactic processing of thematic relationships, as irreversible sentences contained alternative cues for thematic roles. The left anterior negativity likely reflects later processes of rehearsal and reanalysis of sentence content in working memory. PMID- 24227907 TI - PGE 2 desensitizes beta -agonist effect on human lung fibroblast-mediated collagen gel contraction through upregulating PDE4. AB - In the current study, we investigated the effect of a long-acting beta -agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10(-7) and 10(-6) M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10(-5) M). In the presence of 10(-8) M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10(-7) ~10(-5) M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. Pretreatment with PGE2 abolished the inhibitory effect of salmeterol, but it potentiated the inhibitory effect of cilomilast on fibroblast-mediated collagen gel contraction. Finally, indomethacin slightly inhibited PDE4C expression, while PGE2 stimulated the expression of PDE4A and -4C in human lung fibroblasts. These findings suggest that long-acting beta -agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and that PGE2 can modulate the effect of beta -agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression. PMID- 24227909 TI - Gender differences in fat distribution and inflammatory markers among Arabs. AB - Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). OBJECTIVE: To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. METHODS: Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. RESULTS: Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. CONCLUSION: In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men. PMID- 24227908 TI - Topical nonsteroidal anti-inflammatory drugs for macular edema. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. PMID- 24227911 TI - The Pandora's Box. PMID- 24227910 TI - Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy. AB - INTRODUCTION: Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology. METHODS: Twelve retinal samples were taken from patients affected by PVR during therapeutic retinectomies in vitreoretinal surgery. Gene expression was evaluated using quantitative real-time reverse transcriptase PCR analysis and immunohistochemistry, using four healthy human retinae as control. RESULT: Controls showed basal expression of all genes. PVR samples showed little or no expression of Otx1 and variable expression of VEGF-A, Otx2, Otx3, p53, and p63 genes. Significant correlation was found among VEGF-A, Otx2, p53, and p63 and between Otx1 and Otx3. CONCLUSIONS: Otx homeobox, p53 family, and VEGF-A genes are expressed in PVR human retina. We individuated two possible pathways (VEGF-A, Otx2, p53, p63 and Otx1 and Otx3) involved in PVR progression that could influence in different manners the course of the pathology. Individuating the genetic pathways of PVR represents a novel approach to PVR therapies. PMID- 24227912 TI - Orthognathic model surgery by using of a passive Robot Arm. AB - PURPOSE: The possibility of using a passive Robot Arm (3D method) in model surgery and comparing with manual technique model surgery. PATIENTS AND METHODS: Seventeen patients undergoing orthognathic surgery gave consent for this study. Model surgery was performed by using a manual technique and using the Robot Arm. The model surgery that was performed by using the manual technique named group A and the one performed by the Robot Arm named group B. Patients' maxillary casts were measured before and after model surgery, and results were compared with those for the original treatment plan in the horizontal (X-axis), vertical (Y axis), and transverse (Z-axis) planes. RESULTS: Statistical analysis using Mann Whitney U test for X- and Y-axis and independent sample t test for Z-axis have shown significant differences between both groups in X-axis (P = .026) and Y-axis (P = .021) but not in Z-axis (P = .762). CONCLUSIONS: Model surgery performed with a Robot Arm is more accurate in all dimensions X, Y, and Z than the manual model surgery. PMID- 24227914 TI - Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa. AB - PURPOSE: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. METHODS: We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500*l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. RESULTS: Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. CONCLUSIONS: Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases where conventional genetic approaches have previously failed in achieving a proper diagnosis. PMID- 24227913 TI - Regional replication of association with refractive error on 15q14 and 15q25 in the Age-Related Eye Disease Study cohort. AB - PURPOSE: Refractive error is a complex trait with multiple genetic and environmental risk factors, and is the most common cause of preventable blindness worldwide. The common nature of the trait suggests the presence of many genetic factors that individually may have modest effects. To achieve an adequate sample size to detect these common variants, large, international collaborations have formed. These consortia typically use meta-analysis to combine multiple studies from many different populations. This approach is robust to differences between populations; however, it does not compensate for the different haplotypes in each genetic background evidenced by different alleles in linkage disequilibrium with the causative variant. We used the Age-Related Eye Disease Study (AREDS) cohort to replicate published significant associations at two loci on chromosome 15 from two genome-wide association studies (GWASs). The single nucleotide polymorphisms (SNPs) that exhibited association on chromosome 15 in the original studies did not show evidence of association with refractive error in the AREDS cohort. This paper seeks to determine whether the non-replication in this AREDS sample may be due to the limited number of SNPs chosen for replication. METHODS: We selected all SNPs genotyped on the Illumina Omni2.5v1_B array or custom TaqMan assays or imputed from the GWAS data, in the region surrounding the SNPs from the Consortium for Refractive Error and Myopia study. We analyzed the SNPs for association with refractive error using standard regression methods in PLINK. The effective number of tests was calculated using the Genetic Type I Error Calculator. RESULTS: Although use of the same SNPs used in the Consortium for Refractive Error and Myopia study did not show any evidence of association with refractive error in this AREDS sample, other SNPs within the candidate regions demonstrated an association with refractive error. Significant evidence of association was found using the hyperopia categorical trait, with the most significant SNPs rs1357179 on 15q14 (p=1.69*10-3) and rs7164400 on 15q25 (p=8.39*10-4), which passed the replication thresholds. CONCLUSIONS: This study adds to the growing body of evidence that attempting to replicate the most significant SNPs found in one population may not be significant in another population due to differences in the linkage disequilibrium structure and/or allele frequency. This suggests that replication studies should include less significant SNPs in an associated region rather than only a few selected SNPs chosen by a significance threshold. PMID- 24227915 TI - Cataract-specific posttranslational modifications and changes in the composition of urea-soluble protein fraction from the rat lens. AB - PURPOSE: To determine age-related changes in the composition of the urea-soluble (US) protein fraction from lenses of senescence-accelerated OXYS (cataract model) and Wistar (control) rats and to establish posttranslational modifications (PTMs) occurring under enhanced oxidative stress in OXYS lenses. METHODS: The identity and the relative abundance of crystallins in the US fractions were determined using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MS). The identities and the positions of PTMs were established using MS/MS measurements. RESULTS: Two dimensional gel electrophoresis maps of US protein fractions were obtained for lenses of 3-, 12-, and 62-week-old Wistar and OXYS rats, and the relative abundance of different isoforms of alpha-, beta-, and gamma-crystallins was determined. beta-Crystallins were the major contributor of the US fraction in 3 week-old lenses (above 50%), gamma-crystallins in 12-week-old lenses (50-60%), and in 62-week-old lenses, the contributions from all three crystallin families leveled out. The major interstrain difference was the elevated level of alpha crystallins in the US fraction from 12-week-old OXYS lenses. Spots with increased relative abundance in OXYS maps were attributed to the cataract-specific spots of interest. The crystallins from these spots were subjected to MS/MS analysis, and the positions of acetylation, oxidation, deamidation, and phosphorylation were established. CONCLUSIONS: The increased relative abundance of alpha-crystallins in the US fraction from 12-week-old OXYS lenses points to the fast insolubilization of alpha-crystallins under oxidative stress. Most of the PTMs attributed to the cataract-specific modifications also correspond to alpha crystallins. These PTMs include oxidation of methionine residues, deamidation of asparagine and glutamine residues, and phosphorylation of serine and threonine residues. PMID- 24227916 TI - Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. AB - PURPOSE: X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. METHODS: Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. RESULTS: Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5' region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). CONCLUSIONS: Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes. PMID- 24227917 TI - Evaluation of PRSS56 in Chinese subjects with high hyperopia or primary angle closure glaucoma. AB - PURPOSE: Mouse serine protease 56 (Prss56) mutants show a phenotype of angle closure glaucoma with a shortened ocular axial length. Mutations in the human PRSS56 gene are associated with posterior microphthalmia and nanopthalmos. In this study, variations in PRSS56 were evaluated in patients with either primary angle-closure glaucoma (PACG) or high hyperopia. METHODS: A total of 561 participants were enrolled in this study, including 189 individuals with PACG, 110 individuals with simple high hyperopia (sphere refraction >=+5.00 D), and 262 normal control subjects (-0.5 D=3) level comorbidity. We calculated 1- and 5-year survival in different calendar time periods overall, and by age, sex, and level of comorbidity, and used Cox regression to compute mortality rate ratios (MRR) for each level of comorbidity versus no comorbidity in different calendar time periods. RESULTS: Overall 1-year survival increased from 31% in 2000-2002 to 37% in 2009-2011, while the 5-year survival increased from 10% in 2000-2002 to predicted 13% in 2009-2011 with the largest improvement observed for women and patients less than 80 years. The adjusted 1-year MRR in patients with high comorbidity compared with those without comorbidity was 1.23 (95% confidence interval [CI]: 1.05-1.46) in 2000-2002 and 1.35 (95% CI: 1.17-1.56) in 2009-2011. The corresponding adjusted 5 year MRRs were 1.21 (95% CI: 1.04-1.40) in 2000-2002 and 1.26 (95% CI: 1.11-1.42) in 2009-2011. CONCLUSION: Lung cancer patients' survival increased from 2000 to 2011 in the Central Denmark Region, most prominently for women under 80 years and patients with no, or medium level of comorbidity. Their prognosis remained nonetheless dismal with overall 5-year survival of 13%, and comorbidity remained a negative prognostic factor. PMID- 24227922 TI - Comorbidity and survival of Danish breast cancer patients from 2000-2011: a population-based cohort study. AB - OBJECTIVE: Previous studies have suggested that breast cancer survival in Denmark has improved, primarily in cancer patients without comorbidity. We therefore conducted a population-based cohort study to examine recent temporal changes in survival and mortality among breast cancer patients with different extents of comorbidity. METHODS: We used population-based medical and administrative registries to identify breast cancer patients diagnosed between 2000 and 2011 in the Central Denmark Region. We defined comorbid diseases according to the Charlson Comorbidity Index (CCI), including a history of hospitalization for comorbid disease up to 10 years before breast cancer diagnosis. We studied the impact of comorbidities on overall 1- and 5-year survival in different calendar time periods, using a hybrid analysis for survival prediction in the most recent calendar periods. RESULTS: We included 9,329 breast cancer patients. The proportion of patients within different comorbidity categories remained stable from 2000 to 2011. One-year survival improved from 91% in 2000-2002 to 95% in 2009-2011, while 5-year survival improved from 72% to a predicted 78%. During the entire study period, comorbidity was a strong predictor of the survival of breast cancer patients. However, we observed improvements over time in 1- and 5-year survival for all comorbidity groups. During the 12-year study period, the estimated 5-year survival for patients with a high comorbidity disease burden (CCI score >=3) increased from 25% to a predicted 50%, and their 5-year age adjusted mortality hazard ratio (HR) fell from 4.0 (95% confidence interval [CI]: 3.0, 5.4) to 2.7 (95% CI: 2.0, 3.6), respectively, compared with patients with no comorbid disease. CONCLUSION: Survival of breast cancer patients diagnosed in the Central Denmark Region improved from 2000 to 2011, regardless of the extent of comorbid disease. PMID- 24227920 TI - The impact of comorbidity on cancer survival: a review. AB - BACKGROUND: A number of studies have shown poorer survival among cancer patients with comorbidity. Several mechanisms may underlie this finding. In this review we summarize the current literature on the association between patient comorbidity and cancer prognosis. Prognostic factors examined include tumor biology, diagnosis, treatment, clinical quality, and adherence. METHODS: All English language articles published during 2002-2012 on the association between comorbidity and survival among patients with colon cancer, breast cancer, and lung cancer were identified from PubMed, MEDLINE and Embase. Titles and abstracts were reviewed to identify eligible studies and their main results were then extracted. RESULTS: Our search yielded more than 2,500 articles related to comorbidity and cancer, but few investigated the prognostic impact of comorbidity as a primary aim. Most studies found that cancer patients with comorbidity had poorer survival than those without comorbidity, with 5-year mortality hazard ratios ranging from 1.1 to 5.8. Few studies examined the influence of specific chronic conditions. In general, comorbidity does not appear to be associated with more aggressive types of cancer or other differences in tumor biology. Presence of specific severe comorbidities or psychiatric disorders were found to be associated with delayed cancer diagnosis in some studies, while chronic diseases requiring regular medical visits were associated with earlier cancer detection in others. Another finding was that patients with comorbidity do not receive standard cancer treatments such as surgery, chemotherapy, and radiation therapy as often as patients without comorbidity, and their chance of completing a course of cancer treatment is lower. Postoperative complications and mortality are higher in patients with comorbidity. It is unclear from the literature whether the apparent undertreatment reflects appropriate consideration of greater toxicity risk, poorer clinical quality, patient preferences, or poor adherence among patients with comorbidity. CONCLUSION: Despite increasing recognition of the importance of comorbid illnesses among cancer patients, major challenges remain. Both treatment effectiveness and compliance appear compromised among cancer patients with comorbidity. Data on clinical quality is limited. PMID- 24227924 TI - Comorbidity and survival of Danish patients with colon and rectal cancer from 2000-2011: a population-based cohort study. AB - OBJECTIVE: To evaluate recent trends in the prevalence and impact of comorbidity on colorectal cancer (CRC) survival in the Central Region of Denmark. MATERIAL AND METHODS: Using the Danish National Registry of Patients, we identified 5,777 and 2,964 patients with a primary colon or rectal cancer, respectively, from 2000 through 2011. We estimated survival according to Charlson Comorbidity Index scores and computed mortality rate ratios (MRRs) using Cox proportional hazard regression analysis, adjusting for age and sex. RESULTS: More than one-third of CRC patients had comorbidity at diagnosis. During the study period, 1-year survival increased substantially in colon cancer patients with Charlson score 0 (72% to 80%) and modestly for Charlson score 3+ patients (43% to 46%). Using colon cancer patients with Charlson score 0 as reference, adjusted 1-year MRRs in patients with Charlson score 3+ were 2.19 (95% confidence interval [CI]: 1.57 3.05) in 2000-2002 and 2.56 (95% CI: 1.96-3.35) in 2009-2011. One-year survival after rectal cancer improved from 81% to 87% in patients with Charlson score 0 and from 56% to 60% in Charlson score 3+. Corresponding MRRs in patients with Charlson 3+ were 2.21 (95% CI: 1.33-3.68) in 2000-2002 and 3.09 (95% CI: 1.91 5.00) in 2009-2011 using Charlson score 0 as reference. Five-year MRRs did not differ substantially from 1-year MRRs. CONCLUSION: Comorbidity was common among CRC patients and was associated with poorer prognosis. We observed improved survival from 2000 to 2011 for all comorbidity levels, with least improvement for colon cancer patients with comorbid conditions. PMID- 24227925 TI - Dr taylor and the transylvanian peel. PMID- 24227923 TI - Comorbidity and survival of Danish prostate cancer patients from 2000-2011: a population-based cohort study. AB - OBJECTIVE: We investigated temporal changes in overall survival among prostate cancer (PC) patients and the impact of comorbidity on all-cause mortality. METHODS: We conducted a population-based cohort study in the Central Denmark Region (1.2 million inhabitants). Using medical registries, we identified 7,654 PC patients with first-time PC diagnosis within the period 2000-2011 and their corresponding comorbidities within 10 years prior to the PC diagnosis. We estimated 1- and 5-year survival in four consecutive calendar periods using a hybrid analysis and plotted Kaplan-Meier survival curves. We used Cox proportional hazards regression to compute 1- and 5-year age-adjusted mortality rate ratios (MRRs) for different comorbidity levels. All estimates are reported with their corresponding 95% confidence intervals (CI). RESULTS: The annual number of PC cases doubled over the 12-year study period. Men aged <70 years accounted for the largest proportional increase (from 33% to 47%). The proportion of patients within each comorbidity category remained constant over time. One year survival increased from 82% (CI: 80%-84%) in 2000-2002 to 92% (CI: 90%-93%) in 2009-2011, while 5-year survival increased from 43% (CI: 40%-46%) to 65% (CI: 62%-67%) during the same time intervals. Improvements in 5-year survival were most prominent among patients aged <80 years and among those with no comorbidity (from 51% to 73%) and medium comorbidity (from 32% to 54%). Improvements in survival were much smaller for those with high comorbidity (from 33% to 39%). The 1-year age-adjusted MRR for patients with high comorbidity (relative to patients with no comorbidity) increased over time from 1.84 (CI: 1.19-2.84) to 3.67 (CI: 2.49-5.41), while the 5-year age-adjusted MRR increased from 1.73 (CI: 1.34-2.23) to 2.38 (CI: 1.93-2.94). CONCLUSION: Overall survival of PC improved substantially during 2000-2011, although primarily among men with low comorbidity. All-cause mortality was highest among PC patients with high comorbidity, and their relative 1- and 5-year mortality increased over time compared to those without comorbidity. PMID- 24227926 TI - A double-blind randomized controlled trial showing the analgesic and anesthetic properties of lidocaine E to be equivalent to those of ropivicaine and bupivacaine in carpal tunnel release surgery. AB - In a three-phase trial, the anesthetic properties of lidocaine, bupivacaine and ropivicaine were compared in carpal tunnel release surgery. In phase I, two groups of 25 sequential patients were injected with either lidocaine plain 2% or lidocaine 2% with adrenaline 1:100,000 (E), as the local anesthetic for outpatient carpal tunnel release surgery. Subjective injection pain, postoperative pain at 2 h increments and the number of analgesic pills taken were recorded. During the first postoperative hours, outcome measures were superior in the lidocaine E group. In phase II, a double-blind randomized design compared 42 patients injected with either lidocaine E or a combination of lidocaine E and bupivacaine. Postoperative pain scores and analgesic pills taken were compared using nonparametric statistical tests. During the first 4 h there was a slight benefit in the duration of the anesthetic and fewer pain pills were used in the bupivacaine group. Phase III was a randomized double-blind comparison of ropivicaine and lidocaine E 2% in 72 patients. There was a slight decrease in pain scores and fewer analgesic pills required during the first 6 h in the ropivicaine group. Lidocaine plain 2% provided significantly inferior analgesic and anesthetic properties compared with lidocaine E 2%, bupivacaine or ropivicaine. Sequential randomized comparisons between lidocaine E and bupivacaine and ropivicaine showed clinical equivalence. The present study showed lidocaine E 2% to be a satisfactory and comparatively cost-effective anesthetic for outpatient carpal tunnel surgery. PMID- 24227927 TI - Fasciocutaneous cubital flap in soft tissue loss of the wrist. AB - Surgical managment of soft tissue loss in the wrist consists of suitable coverage for the protection of vascular, nervous and tendinous structures. The fasciocutaneous cubital flap covers wrist defects, providing safe support over the nerves, tendons and vessels. Reported here is five cases of wrist defects by different etiology (extravasations, autolysis, trauma and neuritis). A fasciocutaneous cubital flap successfully covered the soft tissue loss in all cases. This flap is applied in an easy, one-stage procedure and it maintains the major arteries of the forearm. PMID- 24227928 TI - Analysis of reporting return to work in studies comparing open with endoscopic carpal tunnel release: A review of randomized controlled trials. AB - BACKGROUND: In studies comparing open with endoscopic carpal tunnel release, return to work (RTW) is often cited as a primary outcome. OBJECTIVE: The present study assessed the reporting of RTW and evaluated its usefulness in studies comparing these two methods of carpal tunnel release. METHODS: A computerized search was conducted to find randomized controlled trials that compared open with endoscopic carpal tunnel release, with RTW as an outcome measure. The factors that were compared across the studies included definition of RTW, units quantifying RTW, measures of hand function, patients' type of employment, worker's compensation or insurance status, patients' handedness, unilateral or bilateral carpal tunnel release, and use of rehabilitation. RESULTS: Fifteen studies met the inclusion criteria for the present systematic review. Of the 15 studies reviewed, there were seven definitions of RTW. All studies defined whether the patients underwent unilateral or bilateral carpal tunnel release but there was variability in the calculation of RTW when bilateral releases were performed. The impact of worker's compensation or insurance, type of work, handedness and rehabilitation were inconsistently addressed as factors affecting RTW. CONCLUSIONS: Although RTW ideally reflects function and recovery, it is inadequately measured and reported. The present review revealed that, in studies comparing open carpal tunnel release with endoscopic carpal tunnel release, there is lack of uniformity in reporting RTW, which may contribute to the inconclusive results for RTW. Future research needs to ensure that RTW is used in a consistent manner. PMID- 24227929 TI - A review of 2975 consecutive operations by one surgeon in an accredited outpatient plastic surgicentre: A Canadian experience. AB - The present paper constitutes a retrospective review of 2975 consecutive operations performed by the author, one of the three owners of the Saskatoon Plastic Surgicentre. The unit opened in 1987; therefore, the study spans 17 years. Patients are not kept overnight, and the Surgicentre is approved and equipped as a level C facility for general anesthesia. Only patients who score 1 or 2 according to the American Association of Anesthesiologists are treated. Only certified anesthesiologists are used. Of the patients with postoperative complications, only two required transfer to a hospital. One developed a pneumothorax, which was treated on arrival at the intensive care unit with no sequelae. The other collapsed following facelift surgery. She was transferred to University of Saskatchewan hospital and died later that evening with a massive pulmonary embolus. In a properly established outpatient centre, a large number of patients can be safely treated with very few complications. However, despite placing patient safety as the first consideration and adhering strictly to the highest standards, death can occur. PMID- 24227930 TI - Maxillofacial injuries in moose-motor vehicle collisions versus other high-speed motor vehicle collisions. AB - BACKGROUND: Anecdotal experience has suggested that there is a higher frequency of maxillofacial injuries among motor vehicle collisions involving moose. OBJECTIVES: A retrospective cohort study design was used to investigate the incidence of various injuries resulting from moose-motor vehicle collisions versus other high-speed motor vehicle collisions. METHODS: A chart review was conducted among patients presenting to a Canadian regional trauma centre during the five-year period from 1996 to 2000. RESULTS: Fifty-seven moose-motor vehicle collisions were identified; 121 high-speed collisions were randomly selected as a control group. Demographic, collision and injury data were collected from these charts and statistically analyzed. The general demographic features of the two groups were similar. Moose collisions were typically frontal impact resulting in windshield damage. The overall injury severity was similar in both groups. Likewise, the frequency of intracranial, spinal, thoracic and extremity injuries was similar for both groups. The group involved in collisions with moose, however, was 1.8 times more likely then controls to sustain a maxillofacial injury (P=0.004) and four times more likely to sustain a maxillofacial fracture (P=0.006). CONCLUSIONS: Occupants of motor vehicles colliding with moose are more likely to sustain maxillofacial injuries than those involved in other types of motor vehicle collisions. It is speculated that this distribution of injuries relates to the mechanism of collision with these large mammals with a high centre of gravity. PMID- 24227931 TI - A new agent for flap survival - Hippophae rhamnoides L. (sea buckthorn): An experimental study in rats. AB - Hippophae rhamnoides L. (sea buckthorn) is a member of the Elaeagnaceae family, and is a temperate bush native to Europe and Asia. The antioxidant activity of H rhamnoides L. has been shown in vitro cell culture and animal studies. Different fractions of H rhamnoides L. fruits inhibit 2,2-azobis-(2,4 dimethylvaleronitrile) and ascorbate iron-induced lipid peroxidations in vitro. H rhamnoides L., as well as vitamin E, decrease the malondialdehyde content in hyperlipidemic rabbit serum-cultured smooth muscle cells. The aim of the present study was to investigate, in a rat model, the potential effect of H rhamnoides L. on survival of random pattern skin flaps. For this purpose, 30 Wistar Albino rats were used, and a McFarlane-type caudally based skin flap was created on the dorsum of the rat (2.5 cm * 8 cm). Rats were divided into three groups: one control (group A) and two treatment groups (groups B and C). H rhamnoides L. was administered orally to the experimental groups: group B received a single 15 mg/kg dose per day and group C received 15 mg/kg twice per day. The areas and lengths of flap necrosis were measured in each group. The extent of necrotic flap areas were evaluated as length and area of total flap area, and differences were studied by Student's t tests. The areas and lengths of necrosis of skin flaps decreased depending on H rhamnoides L., but viability of the flaps treated with 15 mg/kg/day was not significantly different from the control group. The rats receiving H rhamnoides L. 15 mg/kg twice per day had the highest flap survival rate (P<0.001). In conclusion, H rhamnoides L. may have a dose-dependent effect to increase flap survival in random skin flaps. PMID- 24227933 TI - Compression neuropathy of the median nerve during tissue expansion of the forearm. AB - Acute median nerve compression usually occurs from increased pressure within the compartments. During tissue expansion of the forearm, the interstitial pressure increases, which usually decreases following the relaxation of tissue. Clinical diagnosis of acute neuropathy is usually made from the history and clinical signs and symptoms. The cases of two patients who developed acute symptoms of neuropathy during tissue expansion of the forearm are presented. PMID- 24227932 TI - Digital Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is a rare and biologically aggressive neuroendocrine tumour of the skin. Recent analysis of a surveillance, epidemiology and end results program has shown a statistically significant increase of 8% per year in the age-adjusted rates for MCC of the skin over the past 15 years. MCC commonly presents as a painless, rapidly growing, single red or purple cutaneous nodule. Diagnosis is often delayed until histopathological examination due to the relative rarity of the disease. MCC-specific immunohistochemical markers are available for definitive diagnosis, including anticytokeratin-20-positive stain and thyroid transcription factor-1-negative stains. Because there are no phase III trials to guide management, treatment is often tailored to the individual patient by integrating surgery, radiation and chemotherapy. PMID- 24227934 TI - Scrotal and penile reconstruction using the vacuum-assisted closure device. AB - Fournier's gangrene is a necrotizing, soft tissue infection that spreads along the deep external fascial planes of the perineum, scrotum (or vagina), penis, thighs and lower abdomen. Due to the rapid progression of the disease, patients are frequently left with a large integumentary deficit. Treatment of the skin defect has been described in a multitude of ways including split-thickness skin grafting, burying the testes in the thighs, thigh flaps and a variety of myocutaneous and fasciocutaneous flaps. Many of the previously described techniques have worked well for smaller defects and for closure of wounds but fall short of aesthetic reconstruction of sexual organs. Described here is a technique using split-thickness skin grafts, with foam dressings as the bolster. This was performed using the vacuum-assisted closure device (Kinetic Concepts Inc, USA). This technique creates a natural appearing scrotum that holds the testes away from the body, in a physiological manner, and surfaces the penis with a natural appearance, in a functional manner. The technique results in nearly 100% graft take and greatly decreases length of hospital stay. PMID- 24227935 TI - A midface swelling in a child - A possible diagnostic dilemma. AB - A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma. A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented. PMID- 24227936 TI - Reconstruction of a transmetatarsal amputation stump using a salvaged peroneal artery fasciocutaneous flap from the opposite leg: A case report. AB - During lower extremity amputation, the objective is to provide a functional residual limb that permits maximum patient mobility and independence. Preservation of length of the fore part of the foot using salvageable tissue from the amputated part in young patients prevents equines deformity and revision of amputation to a higher level. This can be achieved using tissue available from the amputated part. The spare part concept in reconstructive surgery should be integrated into the trauma algorithm to avoid additional donor site morbidity. Reported here is a young adult patient with crush injuries to both feet, which resulted in amputations. A fasciocutaneous flap raised from one extremity was used to facilitate transmetatarsal amputation stump length preservation of the other extremity. PMID- 24227937 TI - Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development. PMID- 24227938 TI - Effects of vitamin d on blood pressure and endothelial function. AB - Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine. PMID- 24227939 TI - Chronic administration of baicalein decreases depression-like behavior induced by repeated restraint stress in rats. AB - Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression. PMID- 24227940 TI - Sex Differences in Hippocampal Neuronal Sensitization by Nicotine in M. gerbils. AB - We studied the sex different nicotine effect on evoked population spike amplitudes (ePSA) and connexin (Cx) expression in the hippocampus CA1 area of gerbils. Acute doses of nicotine bitartrate (0.5 mg/kg: NT-0.5) slightly reduced ePSA in males but markedly augmented that in females. Acute NT (5.0 mg/kg) markedly increased the ePSA in all gerbils. Unlike acute NT-0.5, repeated NT-0.5 injection (twice a day for 7 days) significantly increased the ePSA in males and slightly affected the NT-0.5 effect in females. The Cx36 and Cx43 expression levels as well as Cx expressing neuronal populations were significantly increased by repeated NT-0.5 in in both male and female gerbils, and particularly, Cx43 expression was somewhat prominent in females. These results demonstrated a sex difference with respect to the nicotine effect on hippocampal bisynaptic excitability, irrelevant to connexin expression. PMID- 24227941 TI - Gastroprotective effect of the three glucuronopyranoside flavonoids in rats. AB - In this study, we investigated the protective action of glucuronopyranoside flavonoids (QGC, AGC, LGC) on gastritis in rats. QGC, AGC and omeprazole decreased the gastric volume significantly, and each ID50 was 0.75, 0.54 and 8.5 mg/kg, respectively, thus the order of potency was AGC, QGC and omeprazole. They also decreased acid output, and each ID50 was 7.81, 0.58 and 6.71 mg/kg, respectively, thus the order of potency was AGC, omeprazole and QGC. They inhibited gastritis induced by indomethacin, and it recovered significantly by increasing the GSH levels in gastritis. The gastric MPO activity in the gastritis group increased more than in the normal group. QGC, LGC, or AGC administration reduced moderately the MPO activity in a dose-dependent manner. This study demonstrated that AGC, QGC, or LGC showed potent efficacy on the gastritis, by preventing oxidative stress. These results suggest that QGC, AGC, or LGC have gastroprotective effect in rats. PMID- 24227942 TI - Ineffective doses of dexmedetomidine potentiates the antinociception induced by morphine and fentanyl in acute pain model. AB - The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 u g/kg. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 ug/kg fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 u g/kg (subcutaneously) to Group 5, dexmedetomidine 3 ug/kg (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 ug/kg dexmedetomidine (subcutaneous)+5 ug/kg fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl. PMID- 24227943 TI - Estrogen rather than progesterone cause constipation in both female and male mice. AB - Females are more often affected by constipation than males, especially during pregnancy, which is related to the menstrual cycle. Although still controversial, alterations of progesterone and estrogen may be responsible. Therefore, this study was conducted in order to determine whether the female sex steroid hormone itself is responsible for development of constipation in both female and male mice. Administration of estrogen resulted in a decrease in weight of accumulated feces on days 2, 3, 4, and 5 in male mice and on day 5 in female mice, compared with the control group, but progesterone administration did not. Administration of estrogen resulted in a decrease in gastrointestinal movement, compared to normal; however, no significant change was observed by administration of progesterone. In conclusion, estrogen, rather than progesterone, may be a detrimental factor of constipation via decreased bowel movement in mice. PMID- 24227944 TI - Activation of G Proteins by Aluminum Fluoride Enhances RANKL-Mediated Osteoclastogenesis. AB - Receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis is accompanied by intracellular Ca(2+) mobilization in a form of oscillations, which plays essential roles by activating sequentially Ca(2+)/calmodulin-dependent protein kinase, calcineurin and NFATc1, necessary in the osteoclast differentiation. However, it is not known whether Ca(2+) mobilization which is evoked in RANKL-independent way induces to differentiate into osteoclasts. In present study, we investigated Ca(2+) mobilization induced by aluminum fluoride (AlF4 (-)), a G-protein activator, with or without RANKL and the effects of AlF4 (-) on the osteoclastogenesis in primary cultured mouse bone marrow-derived macrophages (BMMs). We show here that AlF4 (-) induces intracellular Ca(2+) concentration ([Ca(2+)]i) oscillations, which is dependent on extracellular Ca(2+) influx. Notably, co-stimulation of AlF4 (-) with RANKL resulted in enhanced NFATc1 expression and formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells. Additionally, we confirmed that mitogen activated protein kinase (MAPK) is also activated by AlF4 (-). Taken together, these results demonstrate that G-protein would be a novel modulator responsible for [Ca(2+)]i oscillations and MAPK activation which lead to enhancement of RANKL mediated osteoclastogenesis. PMID- 24227945 TI - Antiapoptotic Effect of Paricalcitol in Gentamicin-induced Kidney Injury. AB - While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 ug/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK. PMID- 24227946 TI - Anti-Depressant Like Effect of Methyl Gallate Isolated from Acer barbinerve in Mice. AB - In the present study, the anti-depressant like effect of methyl gallate (MG) isolated from the stem bark of Acer barbinerve was examined in ICR mice. Body weight (BDW) and blood glucose (BDG) levels significantly decreased in the repeated restraint stress (RRS) group (2 h/day for 14 days) compared to the no stress (NS) group. To examine the effect of MG on RS-induced BDW loss and hypoglycemia, MG (10 mg/kg) and the anti-depressant fluoxetine (10 mg/kg) were administered daily for 14 days. Orally administered MG and fluoxetine significantly attenuated the RS-induced BDW loss and hypoglycemia. Interestingly, MG administered mice showed increased BDG levels in the normal and glucose feeding condition. Chronic RS-subjected mice showed immobilized and depressed behaviors. The effect of MG on the depressed behaviors was evaluated using the tail-suspension test (TST) and the forced swimming test (FST). In both tests, RS induced immobilized behaviors were significantly reversed in MG and fluoxetine administered groups. Taken together, MG significantly attenuated the RS-induced BDW loss, hypoglycemia, and depressed behaviors. Considering that decreased BDG levels (hypoglycemia) can cause depression, MG may exert its anti-depressant like effect by preventing hypoglycemia. Our results suggest that MG isolated from A. barbinerve can exert anti-depressant like effect, and could be used as a new and natural anti-depressant therapy. PMID- 24227947 TI - Nectandrin A Enhances the BMP-Induced Osteoblastic Differentiation and Mineralization by Activation of p38 MAPK-Smad Signaling Pathway. AB - Osteoblastic activity of nectandrin A was examined in C2C12 cells. Nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and increased calcium contents. In C2C12 cells co transfected with expression vector encoding Smad4 and Id1-Luc reporter, nectandrin A increased Id1 luciferase activity in a concentration-dependent manner, when compared to that in BMP-2 treated cells, indicating that Smad signaling pathway is associated with nectandrin A-enhanced osteoblastic differentiation in C2C12 cells. In addition, nectandrin A activated p38 mitogen activated protein kinase (MAPK) in time- and concentration-dependent manners, and phosphorylated form of pSmad1/5/8 and alkaline phosphatase activity were both decreased when the cells were pretreated with SB203580, a p38 MAPK inhibitor, suggesting that p38 MAPK might be an upstream kinase for Smad signaling pathway. Taken together, nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization of C2C12 cells via activation of p38 MAPK-Smad signaling pathway, and it has a therapeutic potential for osteoporosis by promoting bone formation. PMID- 24227948 TI - The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice. AB - Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment. PMID- 24227949 TI - Disappearance of hypoxic pulmonary vasoconstriction and o2-sensitive nonselective cationic current in arterial myocytes of rats under ambient hypoxia. AB - Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K(+) channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A2 (TXA2) and hypoxia-activated nonselective cation channel (INSC) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and TXA2-activated INSC was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased INSC might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia. PMID- 24227950 TI - Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats. AB - This study investigated effect of extract containing quercetin-3-O-beta-D glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation. PMID- 24227952 TI - Glutamic acid as anticancer agent: An overview. AB - The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed. PMID- 24227951 TI - Polymers influencing transportability profile of drug. AB - Drug release from various polymers is generally governed by the type of polymer/s incorporated in the formulation and mechanism of drug release from polymer/s. A single polymer may show one or more mechanisms of drug release out of which one mechanism is majorly followed for drug release. Some of the common mechanisms of drug release from polymers were, diffusion, swelling, matrix release, leaching of drug, etc. Mechanism or rate of drug release from a polymer or a combination of polymers can be predicted by using different computational methods or models. These models were capable of predicting drug release from its dosage form in advance without actual formulation and testing of drug release from dosage form. Quantitative structure-property relationship (QSPR) is an important tool used in the prediction of various physicochemical properties of actives as well as inactives. Since last several decades QSPR has been applied in new drug development for reducing the total number of drugs to be synthesized, as it involves a selection of the most desirable compound of interest. This technique was also applied in predicting in vivo performance of drug/s for various parameters. QSPR serves as a predictive tool to correlate structural descriptors of molecules with biological as well as physicochemical properties. Several researchers have contributed at different extents in this area to modify various properties of pharmaceuticals. The present review is focused on a study of different polymers that influence the transportability profiles of drugs along with the application of QSPR either to study different properties of polymers that regulate drug release or in predicting drug transportability from different polymer systems used in formulations. PMID- 24227953 TI - Current practices for labeling medications in hospitals in Riyadh, Saudi Arabia. AB - BACKGROUND: Good medication labeling practices are imperative to ensure safe medication use. Non-adherence to labeling protocols is reported as one major source of medication errors. OBJECTIVE: This study was intended to evaluate and compare adherence to labeling guidelines for dispensed medications among the hospitals of the five different health sectors in the city of Riyadh, Saudi Arabia. METHODS: A descriptive, cross-sectional analysis was conducted among 14 public hospitals in the city of Riyadh, Saudi Arabia. Labeling guidelines issued by the Institute for Safe Medication Practices were used as a standard assessment tool. A total of 218 medication labels were collected and evaluated for labeling adequacy. Descriptive statistics were used to elaborate the study findings. All analyses were performed with Microsoft Access. RESULTS: The study showed a substantial rate of adherence to the labeling guidelines. In terms of the established criteria, community and mail orders were reported to adhere strongly (90.5%), whereas injectables adhered least to the labeling guidelines. The labeling format, contents of the label, instructions on the labels, abbreviations used on the labels and drug names were also consistent with the guidelines (80.0%, 84.0%, 88.0%, 97.7% and 85.5%, respectively). Organizations belonging to the public sector reported a higher level of adherence (?80.0%) than the level found for private hospitals (70.0%). CONCLUSION: In Riyadh hospitals, medication labeling following the guidelines issued by the Institute for Safe Medication Practices, is well accepted and rationally practiced. However, a nationwide study is recommended to evaluate if the guidelines are followed throughout Saudi Arabia. PMID- 24227954 TI - Availability and needs of herbal medicinal information resources at community pharmacy, Riyadh region, Saudi Arabia. AB - A cross-sectional survey of community pharmacists in Riyadh region, Saudi Arabia was conducted over a period of 6 months from July through December 2011. Data collection was carried out using a structured self-administered questionnaire. The survey questionnaire consisted of a brief introduction to the study and eleven questions. The questions consisted of close ended, multiple-choice, and fill-in short answers. A stratified random sample of one thousand and seven hundred registered pharmacy practitioners all over Saudi Arabia were randomly chosen to respond to the survey. The data from each of the returned questionnaire were coded and entered into Statistical Package for the Social Sciences (SPSS) version 19 software (SPSS Inc., Chicago, IL, USA) which was used for statistical analysis. Only one thousand four hundred one pharmacists responded to the survey (response rate is 82.4%) with a completely answered questionnaire. The study results show that 59.7% of the participants sometimes discuss herbal medicine use with their patients, while only 4.25% never discuss it. The study shows 48.5% of participated pharmacists record herbal medicine use sometimes where only 9.4% of them never did so. However, with regard to initiation of the discussion, the study shows that 44.3% of the respondents reported that patients initiate herbal issue discussion while 20.8% reported that pharmacists initiate the discussion. This discussion was reported to be a one time discussion or an ongoing discussion by 14.3% or 9.9% of the respondents respectively. According to the study results, respondents reported that the most common barriers that limit discussing herbal medicines' use with their patients were lack of time due to other obligations assigned to the community pharmacist (46%), lack of reliable resources (30.3%), lack of scientific evidence that support herbal medicine use (15.2%), or lack of knowledge of herbal medicines (13.4%). Yet, a small number of respondents was concerned about interest in herbal medicines (9.1%) and other reasons (2.4%). So it is urgent to ensure that pharmacists are appropriately educated and trained. Extra efforts are needed to increase the awareness of pharmacists to adverse drug reactions reporting system at Saudi Food and Drug Authority. Finally, more consideration to herbal issues should be addressed in both pharmacy colleges' curricula and continuous education program.. PMID- 24227955 TI - Hospital pharmacy practice in Saudi Arabia: Drug monitoring and patient education in the Riyadh region. AB - BACKGROUND: The purpose of this national survey is to evaluate hospital pharmacy practice in the Riyadh region of Saudi Arabia. The results of the survey pertaining to the monitoring and patient education of the medication use process were presented. METHODS: We have invited pharmacy directors from all 48 hospitals in the Riyadh region to participate in a modified-American Society of Health System Pharmacists (ASHP) survey questionnaire. The survey was conducted using similar methods to those of the ASHP surveys. RESULTS: The response rate was 60.4% (29/48). Most hospitals (23, 79%) had pharmacists regularly monitor medication therapy for patients. Of these hospitals, 61% had pharmacists monitoring medication therapy daily for less than 26% of patients, 17% monitored 26-50% of patients and 22% monitored more than half of patients daily. In 41% of hospitals, pharmacists routinely monitored serum medication concentrations or their surrogate markers; 27% gave pharmacists the authority to order initial serum medication concentrations, and 40% allowed pharmacists to adjust dosages. Pharmacists routinely documented their medication therapy monitoring activities in 52% of hospitals. Overall, 74% of hospitals had an adverse drug event (ADE) reporting system, 59% had a multidisciplinary committee responsible for reviewing ADEs, and 63% had a medication safety committee. Complete electronic medical record (EMR) systems were available in 15% of hospitals and 81% had a partial EMR system. The primary responsibility for performing patient medication education lays with nursing (37%), pharmacy (37%), or was a shared responsibility (26%). In 44% of hospitals, pharmacists provided medication education to half or more inpatients and in a third of hospitals, pharmacists gave medication education to 26% or more of patients at discharge. CONCLUSION: Hospital pharmacists in the Riyadh region are actively engaged in monitoring medication therapy and providing patient medication education, although there is considerable opportunity for further involvement. PMID- 24227956 TI - Impact of clinical pharmacist on cost of drug therapy in the ICU. AB - OBJECTIVE: To determine whether the presence of Clinical Pharmacist affects the cost of drug therapy for patients admitted to the Intensive Care Unit (ICU) at Al Hussein hospital at Royal Medical Services in Amman, Jordan. METHOD: This study compares the consumed quantities of drugs over two periods of time. Each period was ten months long. In the second period there was a Clinical Pharmacist. The decrease in consumption rate of drugs is considered to be an indicator of the success of Clinical Pharmacist in the ICU, as any decrease in consumption rate reflects the correct application of Clinical Pharmacy practices. The cost of this decrease in consumption rate represents the total reduction of drug therapy cost. RESULTS: The total reduction of drug therapy cost after applying Clinical Pharmacy practices in the ICU over a period of ten months was 149946.80 JD (211574.90 USD), which represents an average saving of 35.8% when compared to the first period in this study. CONCLUSION: The results of this study showed a significant reduction in the consumed quantities of drugs and therefore a reduction in cost of drug therapy. Such findings highlight the importance of the presence of Clinical Pharmacist in all Jordanian hospitals wards and units. PMID- 24227957 TI - A study assessing the impact of different teaching modalities for pharmacy students in a Cardio-Pulmonary Resuscitation (CPR) course. AB - The current study aims to assess the effectiveness of different teaching methods adopted for the practical session of Cardio-Pulmonary Resuscitation (CPR). CPR training is one of the compulsory modules of the Public Health Pharmacy (PHP) course at Universiti Sains Malaysia. CPR training comprises of 10% of total marks of the PHP course. To test the effectiveness of the different teaching strategies, three groups were defined using a two-stage cohort distribution-i.e. based on grade point average (GPA) and different teaching modalities. Group One was instructed using images and PowerPoint lecture slides. Group Two was instructed using videos and PowerPoint lecture slides. Group Three was instructed using PowerPoint slides with white boards and videos. Students in Group Three were not provided with a hard/soft copy of the PowerPoint slides and were encouraged to write down all the information on their personal notebooks. A 20 item questionnaire was used to assess the students' understanding toward the CPR session. Data were analyzed using the Statistical Package for Social Science Students, SPSS version 13(r). Based on the response attained, the comparison of the final score among the groups was undertaken using one way ANOVA. Twenty-seven students have participated in this study. Final evaluation using the questionnaire revealed that student's in Group Three had a better understanding of CPR (18.1 +/- 1.5, p <0.001) than the other two. Students' note taking during the lecture and use of traditional chalkboard teaching were found significant to improve the students' understanding and learning in the CPR session. PMID- 24227958 TI - Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. AB - In the present work attempts have been made to prepare the nanostructured lipid carrier (NLC) gel, by using minoxidil, which is preferably used in case of Alopecia, i.e. baldness pattern as a effective drug. The nine different formulations of Minoxidil-NLC (NLC1-NLC9) were prepared using solid and liquid lipids with Cholesterol and Soya lecithin in different concentrations by the melt dispersion ultrasonication method. Properties of NLC1-NLC9 such as the particle size and its distribution, the scanning electron microscopy (SEM), the drug entrapment efficiency (EE), and the drug release behavior were investigated. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadability, rheology, and in vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies. The formulated NLC3 was spherical in shape, with average particle size of 280 nm, zeta potential of -42.40 mV and entrapment efficiency of 86.09%. Differential Scanning Calorimeter (DSC) measurements revealed that imperfect crystallization occurred in the inner core of the NLC particles. The drug release behavior from the NLC displayed a biphasic drug release pattern with burst release at the initial stage followed by sustained release. These results indicated that the NLC3 is a suitable carrier of minoxidil with improved drug loading capacity and controlled drug release properties. It has been observed that NLC gel produces the gel with good consistency, homogeneity, spreadability and rheological behavior. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 16 h. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nanoparticulate form helped us to attain the objective of faster onset yet prolonged action as evident from in vitro release. PMID- 24227959 TI - Evaluation of PEG and mPEG-co-(PGA-co-PDL) microparticles loaded with sodium diclofenac. AB - The aim of this study was to synthesize and evaluate novel biodegradable polyesters namely; poly(ethylene glycol)-Poly(glycerol adipate-co-omega pentadecalactone), PEG-PGA-co-PDL-PEG, and poly(ethylene glycol methyl ether) Poly(glycerol adipate-co-omega-pentadecalactone), PGA-co-PDL-PEGme as an alternative sustained release carrier for lung delivery compared with non-PEG containing polymer PGA-co-PDL. The co-polymers were synthesized through lipase catalysis ring opening polymerization reaction and characterized using GPC, FT IR, (1)H-NMR and surface contact angle. Furthermore, microparticles containing a model hydrophilic drug, sodium diclofenac, were prepared via spray drying from a modified single emulsion and characterized for their encapsulation efficiency, geometrical particle size, zeta potential, tapped density, primary aerodynamic diameter, amorphous nature, morphology, in vitro release and the aerosolization performance. Microparticles fabricated from mPEG-co-polymer can be targeted to the lung periphery with an optimum in vitro deposition. Furthermore, a significantly higher in vitro release (p > 0.05, ANOVA/Dunnett's) was observed with the PEG and mPEG-co-polymers compared to PGA-co-PDL. In addition, these co polymers have a good safety profile upon testing on human bronchial epithelial, 16HBE14o- cell lines. PMID- 24227960 TI - A rat model against chemotherapy plus radiation-induced oral mucositis. AB - OBJECTIVES: Present study was aimed at developing an experimental model of oral mucositis in rats using a combination of chemotherapeutic agent and radiation. STUDY DESIGN: Female Wistar rats (150-200 g) were divided into 3 groups (n = 6). Rats in group 1 (normal control) and group 2 (mucositis control) were treated with vehicle. Rats in group 3 were treated with l-glutamine (1 g/kg, p.o.; 15 days) before and after mucositis induction. Oral mucositis was induced by busulfan (6 mg/kg, p.o.; 4 days) and the tongue exposed to infrared (IR) radiation of intensity 40 mV/cm(2) for 5 s on the 1st, 4th and 10th days of challenge using a tail flick apparatus. Parameters monitored were body weight, food intake, blood count and survival. Oral mucositis score (OMS) was recorded daily. Histological changes of the irradiated tongue were assessed by hematoxylin and eosin staining. RESULTS: Busulfan and IR radiation significantly reduced body weight and food intake of the mucositis control group as compared to normal control. Clear ulceration of the tongue reflected in the OMS. Histopathology of the tongue revealed intense lymphocytic infiltration, decreased thickness of squamous epithelial cell layer, decrease in number of blood vessels, and necrosis of cells along with pseudo-membrane formation in the mucositis control group. These findings suggested that oral mucositis was successfully induced and treatment with l-glutamine partially reversed these conditions. CONCLUSION: Oral mucositis was established successfully in rats by the combination of chemotherapeutic agent and IR radiation. This may be a useful model for screening drugs in the treatment of oral mucositis. PMID- 24227961 TI - A new and simple HPLC method for determination of etamsylate in human plasma and its application to pharmacokinetic study in healthy adult male volunteers. AB - A new and simple HPLC assay method was developed and validated for the determination of etamsylate in human plasma. After protein precipitation with 6% perchloric acid, satisfactory separation was achieved on a HyPURITY C18 column (250 mm * 4.6 mm, 5 MUm) using a mobile phase comprising 20 mM sodium dihydrogen phosphate-2 hydrate (pH was adjusted to 3.5 by phosphoric acid) and acetonitrile at a ratio of 95:5 v/v. The elution was isocratic at ambient temperature with a flow rate of 0.75 ml/min. Allopurinol was used as internal standard. The calibration curve was linear over the range from 0.25 to 20 MUg/ml (r (2) = 0.999). The limit of quantification for etamsylate in plasma was 0.25 MUg/ml. The within day coefficient of variance (%CV) ranged from 3.9% to 10.2%, whereas the between-day %CV ranged from 3.1% to 8.7%. The assay method has been successfully used to estimate the pharmacokinetics of etamsylate after oral administration of a 500 mg tablet under fasting conditions to 24 healthy Egyptian human male volunteers. Various pharmacokinetic parameters including AUC0- t , AUC0-infinity, C max, T max, t 1/2, MRT, Cl/F, and Vd/F were determined from plasma concentration-time profile of etamsylate. PMID- 24227962 TI - A comparative study of validated spectrophotometric and TLC- spectrodensitometric methods for the determination of sodium cromoglicate and fluorometholone in ophthalmic solution. AB - The determination of sodium cromoglicate (SCG) and fluorometholone (FLU) in ophthalmic solution was developed by simple, sensitive and precise methods. Three spectrophotometric methods were applied: absorptivity factor (a-Factor method), absorption factor (AFM) and mean centering of ratio spectra (MCR). The linearity ranges of SCG were found to be (2.5-35 MUg/mL) for (a-Factor method) and (MCR); while for (AFM), it was found to be (7.5-50 MUg/mL). The linearity ranges of FLU were found to be (4-16 MUg/mL) for (a-Factor method) and (AFM); while for (MCR), it was found to be (2-16 MUg/mL). The mean percentage recoveries/RSD for SCG were found to be 100.31/0.90, 100.23/0.57 and 100.43/1.21; while for FLU, they were found to be 100.11/0.56, 99.97/0.35 and 99.94/0.88 using (a-Factor method), (AFM) and (MCR), respectively. A TLC-spectrodensitometric method was developed by separation of SCG and FLU on silica gel 60 F254 using chloroform:methanol:toluene:triethylamine in the ratio of (5:2:4:1 v/v/v/v) as developing system, followed by spectrodensitometric measurement of the bands at 241 nm. The linearity ranges and the mean percentage recoveries/RSD were found to be (0.4-4.4 MUg/band), 100.24/1.44 and (0.2-1.6 MUg/band), 99.95/1.50 for SCG and FLU, respectively. A comparative study was conducted between the proposed methods to discuss the advantage of each method. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the determination of SCG and FLU in their laboratory prepared mixtures and commercial ophthalmic solution in the presence of benzalkonium chloride as a preservative. These methods could be an alternative to different HPLC techniques in quality control laboratories lacking the required facilities for those expensive techniques. PMID- 24227963 TI - Methotrexate for the treatment of generalized vitiligo. PMID- 24227964 TI - Electronic medical records in ophthalmology. PMID- 24227965 TI - Descemet stripping with automated endothelial keratoplasty: A comparative study of outcome in patients with preexisting glaucoma. AB - PURPOSE: To compare postoperative complications after Descemet stripping with automated endothelial keratoplasty (DSAEK) in patients with and without glaucoma. METHODS: For this retrospective study a series of 298 DSAEK cases performed at the Doheny Eye Institute were taken, we compared postoperative complications in eyes with glaucoma on medication (55) or with previous glaucoma surgeries (64) with a time-matched group of all other DSAEK cases (179, control). RESULTS: With a mean follow-up of 1.85 +/- 1.12 years, the complication rates were 12.8%, 11.1%, and 26.8% for postoperative graft detachment, graft failure, and IOP elevation, respectively. Graft detachment was an independent risk factor for graft failure (odds ratio OR = 12.35, 95% confidence interval CI [5.46-27.90], P < 0.001). Graft detachment was not associated with either history of glaucoma or glaucoma surgery (P > 0.05). Glaucoma on medication had no increased risks of graft failure compared to normal eyes (P = 0.38). However, increased risk of failure was seen in eyes with prior incisional glaucoma surgeries (OR = 4.26, 95% CI [1.87-9.71], P < 0.001). Medically managed glaucoma has increased risks of postoperative IOP elevation (OR = 2.39, 95% CI [1.25-4.57], P = 0.013), whereas surgically managed glaucoma has no significant elevation (P = 0.23). Elevation of IOP was not significantly correlated with graft failure (P = 0.21). CONCLUSION: DSAEK is the preferred treatment for corneal endothelial dystrophy. We observed that having glaucoma or glaucoma surgery is not associated with graft detachment. A history of glaucoma surgery and postoperative graft detachment appeared to be important risk factors for graft failure. And more studies are indicated to study long-term IOP evolution in post-DSAEK patients and its association with graft survival. PMID- 24227966 TI - Ranibizumab for idiopathic epiretinal membranes: A retrospective case series. AB - PURPOSE: To study the effect of intravitreal ranibizumab on idiopathic epiretinal membranes (ERMs). METHODS: A retrospective cohort study on a consecutive series of ranibizumab intravitreal injections for epiretinal membranes was performed. Four cases were identified by reviewing a claims database linked to electronic medical records. All patients received a total of three 0.05 mg/0.05 ml ranibizumab intravitreal injections at a monthly interval. The primary outcome measure was the final best-corrected visual acuity (BCVA) at the end of the injection series, and the final central macular thickness (CMT). RESULTS: All four patients completed 3 months follow-up after the last ranibizumab injection. The mean baseline CMT was 509 microns (SD = 111). A trend was noticed for reduction in CMT (Delta = 41 microns) P = 0.08. Three patients improved by one line in their BCVA. The remaining patient maintained the same BCVA. No complications were noted. CONCLUSION: In this study, intravitreal injection of ranibizumab marginally reduced retinal thickness in four patients with minimal improvement in visual acuity. No safety concerns were noticed. Further basic science and clinical studies may be warranted to assess the role of vascular endothelial growth factor and the effect of ranibizumab on idiopathic epiretinal membranes. PMID- 24227967 TI - Effect of Homatropine eye drops on pain after photorefractive keratectomy: A pilot study. AB - PURPOSE: To assess the effect of homatropine eye drops on pain after photorefractive keratectomy (PRK). METHODS: This randomized, double masked, interventional study included 15 patients (30 eyes) who underwent bilateral PRK. After operation, patients received homatropine eye drops, 4 times daily in only one eye (homatropine eye). The level of pain was evaluated using visual analogue scale (VAS), verbal rating scale (VRS) and pain rating index (PRI) at 0.5, 24 and 48 h after operation. RESULTS: The level of pain was statistically similar between the two eyes half an hour after operation, however, homatropine eyes had significantly less pain 24 h after operation compared to fellow eyes (2.5 +/- 1.9 vs 5.3 +/- 2.5, P = 0.004 for VAS, 2.0 +/- 1.2 vs 3.2 +/- 0.9, P = 0.023 for VRS, and 9.4 +/- 5.7 vs 16.0 +/- 9.0, P = 0.031 for PRI). Also, 48 h after surgery, the pain scales were less in the homatropine eyes (2.3 +/- 1.7 vs 4.0 +/- 2.1, P = 0.014 for VAS, 1.6 +/- 1.0 vs 2.5 +/- 1.0, P = 0.038 for VRS, and 6.8 +/- 5.7 vs 12.0 +/- 8.9, P = 0.005 for PRI). No delayed epithelial healing was observed. CONCLUSION: Homatropine eye drops may be useful for reducing pain after Photorefractive keratectomy. PMID- 24227968 TI - Multifocal electroretinogram in diabetic subjects. AB - PURPOSE: To identify local retinal abnormalities and evaluate the nature and extent of retinal dysfunction in diabetics using full field electroretinogram (ERG) and multifocal ERG (MF-ERG) and to determine the correlation between features of optical coherence tomography (OCT) and MF-ERG. METHODS: Twenty-eight normal subjects (Control Group; 56 eyes) and 37 patients (72 eyes) with diabetes mellitus (DM Group) were evaluated. In the DM Group, 17 eyes had no retinopathy (grade 1), 18 eyes had early non proliferative diabetic retinopathy (NPDR) (grade 3), 16 eyes had late NPDR (grade 4), 21 eyes had proliferative diabetic retinopathy (PDR) (grade 5). Full field ERG and MF-ERG, were used to assess the effects of diabetic retinopathy on retinal function. OCT and fluorescein angiography were used to assess and compare morphological changes with functional changes in diabetes mellitus. RESULTS: In diabetic patients without retinopathy (17 eyes), the amplitudes of the second order component of MF-ERG were reduced and implicit times were delayed, while only implicit times of first order component of MF-ERG were delayed but the amplitudes of first order component were normal. In diabetic patients with retinopathy (55 eyes), the overall amplitudes were reduced and peak implicit time increased in the first order component and second order component. OCT of the DM Group showed the fovea of eyes with edema were thicker than the Normal Group. The fovea of eyes with cystoid macular edema (CME) were significantly thicker than the fovea of eyes with diffuse swelling. The implicit times of MF-ERG were directly correlated with foveal thickness. CONCLUSION: MF-ERG reveals local retinal dysfunction in diabetic patients. MF-ERG offers the advantage of topographic mapping of retinal dysfunction. The magnitude of delay of MF-ERG implicit time reflects the degree of local clinical abnormalities in eyes with retinopathy. Local response delays found in eyes without retinopathy detects subclinical local retinal dysfunction in diabetics. The combination of OCT and MF-ERG may provide objective criteria for evaluation and assessment of diabetic retinopathy. PMID- 24227970 TI - The gene therapy revolution in ophthalmology. AB - The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable. PMID- 24227969 TI - The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review. AB - Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinal fluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders. PMID- 24227971 TI - Lacrimal glands in cystic fibrosis. AB - Cystic fibrosis is a systemic disease involving defective mucus secretion in different parts of the body resulting in a wide range of systemic complications. We are presenting the histology of the lacrimal gland from a 25 year old male with cystic fibrosis using light microscopy. To the best of our knowledge this is the first report. PMID- 24227972 TI - Successful treatment of melanocytoma associated choroidal neovascular membrane with intravitreal bevacizumab. AB - Melanocytoma of the optic disc is a benign melanocytic tumour that rarely causes visual impairment. We report a rare case of choroidal neovascularization (CNV) in association with optic disc melanocytoma and its response to intravitreal injection of the anti-vascular endothelial growth factor (VEGF), bevacizumab. The choroidal neovascular membrane regressed following a single intravitreal bevacizumab injection with formation of a scar. CNV associated with optic disc melanocytoma is rare. Intravitreal anti-VEGF treatment may be an effective treatment for CNV associated with optic disc melanocytoma. PMID- 24227973 TI - Monocular elevation deficiency with associated dextrocardia and situs inversus. AB - A patient having monocular elevation deficiency with associated dextrocardia and situs inversus is reported. Review of the literature regarding ocular features described in association with dextrocardia is also presented. PMID- 24227974 TI - Post-LASIK interface fluid syndrome caused by steroid drops. AB - Interface fluid syndrome after laser in situ keratomileusis (LASIK) is a rare but visually threatening postoperative complication. In this case series we present 8 post-LASIK eyes that developed interface fluid syndrome after prolonged steroid use. Patients presented with signs mimicking diffuse lamellar keratitis (DLK) that worsened with steroid treatment. Slit-lamp examination revealed corneal haze and an optically clear fluid-filled space between the flap and stroma. The IOP was high in all cases. Topical steroids were stopped and replaced with topical and systemic anti-glaucoma medications resulting in a dramatic improvement in visual acuity. PMID- 24227975 TI - Ocular tumors: Triumphs, challenges and controversies. PMID- 24227976 TI - Retinoblastoma: A new challenge to the Knudson's Dogma. PMID- 24227977 TI - Diffuse anterior retinoblastoma: A review. AB - Diffuse anterior retinoblastoma is a rare variant of diffuse infiltrating retinoblastoma which occurs in up to 1-2% of cases of retinoblastoma. In diffuse anterior retinoblastoma there is a small focus of tumor in the peripheral retina from which free tumor cells enter the aqueous humor and implant on the ciliary body, iris, lens and trabecular meshwork. Patients most commonly present with pseudouveitis, pseudohypopyon and increased intraocular pressure. The differential diagnosis is broad and all of the reported cases relied upon aspirates from the aqueous humor in order to make the diagnosis prior to proceeding with treatment. Treatment involves enucleation and, depending upon the extent of the tumor, may require systemic chemotherapy or external beam radiation. This review summarizes the 7 previously reported cases of diffuse anterior retinoblastoma, discusses pathologic features, and addresses the challenges of early diagnosis and future directions. PMID- 24227979 TI - Intravitreal chemotherapy for vitreous seeding in retinoblastoma: Recent advances and perspectives. AB - For decades intravitreal chemotherapy (IViC) remained virtually banished from the therapeutic armamentarium against retinoblastoma, except as a heroic attempt of salvage before enucleation in only eyes with refractory vitreous seeding. Very recently, we have initiated a reappraisal of this route of administration by (1) profiling eligibility criteria, (2) describing a safety-enhanced injection procedure, (3) adjusting the tumoricidal dose of melphalan, and (4) reporting an unprecedented efficacy in terms of tumor control of vitreous seeding. Since then, intravitreal chemotherapy is being progressively implemented worldwide with great success, but still awaits formal validation by the ongoing prospective phase II clinical trial. As far as preliminary results are concerned, IViC appears to achieve complete vitreous response in 100% of the 35 newly recruited patients irrespective of the previous treatment regimen, including external beam radiotherapy and/or intra-arterial melphalan. In other words, vitreous seeding, still considered as the major cause of primary and secondary enucleation, can now be controlled by IViC. However, sterilization of vitreous seeding does not necessarily translate into eye survival, unless the retinal source of the seeds receives concomitant therapy. In conclusion, IViC, an unsophisticated and cost effective treatment, is about to revolutionize the eye survival prognosis of vitreous disease in advanced retinoblastoma. PMID- 24227978 TI - Animal models in retinoblastoma research. AB - Advances in animal models of retinoblastoma have accelerated research in this field, aiding in understanding tumor progression and assessing therapeutic modalities. The distinct pattern of mutations and specific location of this unique intraocular tumor have paved the way for two types of models- those based on genetic mutations, and xenograft models. Retinoblastoma gene knockouts with an additional loss of p107, p130, p53 and using promoters of Nestin, Chx10, and Pax6 genes show histological phenotypic changes close to the human form of retinoblastoma. Conditional knockout in specific layers of the developing retina has thrown light on the origin of this tumor. The use of xenograft models has overcome the obstacle of time delay in the presentation of symptoms, which remains a crucial drawback of genetic models. With the advances in molecular and imaging technologies, the current research aims to develop models that mimic all the features of retinoblastoma inclusive of its initiation, progression and metastasis. The combination of genetic and xenograft models in retinoblastoma research has and will help to pave way for better understanding of retinoblastoma tumor biology and also in designing and testing effective diagnostic and treatment modalities. PMID- 24227980 TI - Proton beam radiotherapy of uveal melanoma. AB - Proton beam radiotherapy of uveal melanoma can be administered as primary treatment, as salvage therapy for recurrent tumor, and as neoadjuvant therapy prior to surgical resection. The physical properties of proton beams make it possible to deliver high-doses of radiation to the tumor with relative sparing of adjacent tissues. This form of therapy is effective for a wider range of uveal melanoma than any other modality, providing exceptionally-high rates of local tumor control. This is particularly the case with diffuse iris melanomas, many of which are unresectable. The chances of survival, ocular conservation, visual preservation and avoidance of iatrogenic morbidity depend greatly on the tumor size, location and extent. When treating any side-effects and/or complications, it is helpful to consider whether these are the result of collateral damage or persistence of the irradiated tumor ('toxic tumor syndrome'). PMID- 24227981 TI - Periocular sebaceous gland carcinoma: A comprehensive review. AB - Sebaceous gland carcinoma (SGC) is a rare tumour occurring at periocular and extra-ocular sites. SGC can be a challenging diagnosis for both clinicians and pathologists. High recurrence rates and a tendency for intra-epithelial spread, locoregional and distant metastases make it important for SGC to be suspected and be included in the differential diagnosis of an eyelid lesion. Early diagnosis, that may sometimes need ancillary testing, and prompt management using a multimodal approach can help reduce morbidity and mortality in patients with SGC. PMID- 24227982 TI - Orbital rhabdomyosarcomas: A review. AB - Rhabdomyosarcoma (RMS) is a highly malignant tumor and is one of the few life threatening diseases that present first to the ophthalmologist. It is the most common soft-tissue sarcoma of the head and neck in childhood with 10% of all cases occurring in the orbit. RMS has been reported from birth to the seventh decade, with the majority of cases presenting in early childhood. Survival has changed drastically over the years, from 30% in the 1960's to 90% presently, with the advent of new diagnostic and therapeutic modalities. The purpose of this review is to provide a general overview of primary orbital RMS derived from a literature search of material published over the last 10 years, as well as to present two representative cases of patients that have been managed at our institute. PMID- 24227983 TI - Ocular surface squamous neoplasia - Review of etio-pathogenesis and an update on clinico-pathological diagnosis. AB - Ocular surface squamous neoplasia (OSSN) has a varied clinical presentation, the diagnosis of which rests on the histopathological examination of the excised lesion. The term OSSN includes mild dysplasia on one end of the spectrum and invasive squamous cell carcinoma on the other end. This lesion has a multi factorial aetiology with interplay of several factors like exposure to ultraviolet radiation, various chemical carcinogens and viral infections, however role of individual agents is not well understood. With the upsurge of infection with human immunodeficiency virus, a changing trend is seen in the clinical presentation and prognosis of patients of OSSN even in developed countries. Anterior segment optical coherence tomography (OCT) and confocal microscopy, hold promise in in-vivo differentiation of intraepithelial neoplasia from invasive squamous cell carcinoma. Variants of squamous cell carcinoma like Mucoepidermoid carcinoma, spindle cell carcinoma and OSSN associated with HIV infection should be suspected in a case of aggressive clinical presentation of OSSN or with massive and recurrent tumours. Surgery, chemotherapy and immunotherapy are the various treatment modalities which in combination show promising results in aggressive, recurrent and larger tumours. PMID- 24227984 TI - Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature. AB - Choroidal metastasis is the most common intraocular neoplasm and is associated with significant morbidity. In a small percentage of patients, ocular manifestation may be the initial presentation of a systemic malignancy and can be diagnostically difficult to distinguish from ocular primary malignancies. Herein, we present a case of a never-smoker whose ocular pathology was integral to the diagnosis and management of a lung adenocarcinoma harboring a rare oncogene. Through this case, we have explored important diagnostic and therapeutic considerations of pulmonary metastases to the choroid. PMID- 24227985 TI - Efficacy of vincristine and carboplatin as chemo-reduction for advanced bilateral retinoblastoma, the Saudi experience. AB - PURPOSE: To evaluate the efficacy of a 2-drug chemotherapy regimen without external-beam radiotherapy (EBRT) and/or without enucleation in bilateral retinoblastoma. METHODS: From 1996 to 2010, 79 patients were diagnosed with bilateral RB and were eligible for chemotherapy. Chemotherapy was administered prior to and/or following local therapy to the eye. All patients received 3 cycles of chemo-reduction with carboplatin and vincristine, additional cycles of the same or other chemotherapy, local therapy, EBRT and enucleation were determined according to re-evaluation by the ophthalmologist. RESULTS: Advanced disease was seen in 115 (79%) eyes (group IV and V: 96, Group D and E: 19) out of 146 affected eyes. Tumor response after chemotherapy was observed in 78 patients (98.7%); complete response in 25 (32.1%), partial response in 49 (62.8%) Four (5.1%) had progressive disease. A total of 50 (63.3%) patients required EBRT; 38 for persistent disease, 4 for progressive disease, 2 for new lesions, 2 for re activation and 4 for disease control. Enucleation was required in 15 (19%). Secondary malignancies occurred in two patients who underwent EBRT; one osteogenic sarcoma and one rhabdomyosarcoma then later osteogenic sarcoma. The 10 year overall survival was 96.3% with a median follow-up time of 3.124 +/- 0.536 years (95%CI: 2.074-4.174). CONCLUSIONS: The 2-drug chemotherapy regimen combined with local therapy appears to be adequate therapy for low stage disease but not in patients with advanced disease. The occurrence of secondary cancers in this group of patients is worrisome further highlighting the deleterious effects of EBRT. PMID- 24227986 TI - Uveal melanoma in children and teenagers. AB - PURPOSE: To review the features and prognosis of uveal melanoma in children. METHODS: Retrospective case series. RESULTS: Of 122 children with uveal melanoma, there were 53 (43%) male and 69 (57%) female patients. In this group, the mean age at presentation was 15 years (median 16 years, range 3-20 years). Age at presentation was 0 to 5 years in 4 (3%), 5.1 to 10 years in 14 (11%), 10.1 to 15 years in 43 (35%), and 15.1 to ?20 in 61 (50%). Associated ocular melanocytosis was present in 4 (3%). The melanoma was primarily located in the iris (n = 30, 25%), ciliary body (n = 10, 8%), or choroid (n = 82, 67%). The mean tumor basal dimension was 9.8 mm and mean thickness was 5.0 mm. The tumor color was pigmented (brown) (n = 102, 84%), nonpigmented (yellow) (n = 19, 16%), or mixed (n = 25, 21%). Subretinal fluid (n = 66, 54%) and hemorrhage (n = 9, 7%) were noted. Primary treatment involved laser photocoagulation (n = 3, 2%), transpupillary thermotherapy (n = 17, 14%), local tumor resection (n = 26, 21%), plaque radiotherapy (n = 42, 34%), or enucleation (n = 54, 44%). Kaplan Meier 5, 10, and 20-year estimates for uveal melanoma-related metastasis were 9%, 9%, and 20%, respectively, for children compared to 15%, 25%, and 36% for all ages. CONCLUSION: Uveal melanoma in children tends to occur most often in the teenage years as a pigmented tumor involving the choroid or iris and with mean thickness of 5 mm. Prompt treatment is advised. PMID- 24227987 TI - Secondary glaucoma as initial manifestation of uveal melanoma. AB - PURPOSE: Secondary glaucoma can be induced by a variety of local ocular problems. Intraocular tumors may initially present as secondary glaucoma. METHODS: 8 consecutive patients with secondary glaucoma were found to have uveal melanoma. Thorough examination included detailed history, fundus examination with scleral depression, B scan ultrasonography, and CT/MRI scanning techniques. RESULTS: A single case presented with spontaneous hyphema, two patients presented with secondary glaucoma, extraocular melanoma and metastases, a single case was found to have angle block by an iridociliary ring melanoma and 4 cases presented with neovascular glaucoma. Enucleation was necessary in all 8 cases. CONCLUSIONS: General ophthalmologists should be aware of these rare initial manifestations of intraocular tumors as secondary glaucoma. Enucleation would be recommended in most cases of intraocular malignancy manifesting as secondary glaucoma. One should be extremely cautious in doing a penetrating surgery in such cases. PMID- 24227988 TI - Morphologic changes of the fovea and visual acuity associated with retinal detachment secondary to circumscribed choroidal hemangioma. AB - PURPOSE: To clarify and review the early and late morphologic changes of the macula associating with visual loss in patients with subfoveal fluid secondary to extrafoveal circumscribed choroidal hemangiomas. METHODS: Previously six non treated eyes of six patients with subfoveal retinal detachment secondary to extrafoveal circumscribed choroidal hemangioma were included. Visual acuity (VA), duration of visual symptoms, color fundus photography, optical coherence tomography (OCT), fundus autofluorescence, and fluorescein angiography (FA) were evaluated. RESULTS: The mean patient age was 58 years (range, 25-78). The VA and duration of symptoms in each patient was 1.2 (3 days), 0.6 (1 week), 0.4 (3 months), 0.5 (6 months), 0.02 (12 months), and 0.01 (8 years), respectively. Three patients with symptoms for less than 3 months did not have retinal pigment epithelial (RPE) alterations, retinal edema, or thinning of the retinal structure in the fovea. A patient with symptoms for 3 months had subfoveal deposits underneath the detached neurosensory retina with foveal hyperautofluorescence. Two patients with symptoms exceeding 12 months had highly affected RPE and cystoid macular degeneration. CONCLUSIONS: The VA was affected in patients with longer visual symptoms, and there are some changes in the retina and RPE in the fovea by FA and OCT. Persistent subretinal fluid secondary to choroidal hemangiomas may result in pathologic changes in the neurosensory retina. PMID- 24227989 TI - Ocular manifestations of graft-versus-host disease. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT. Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production. Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva. Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation. PMID- 24227990 TI - The use of forehead flaps in the management of large basal cell carcinomas of the medial canthus/medial lower eyelid in Saudi patients. AB - PURPOSE: Basal cell carcinoma (BCC) is the most common skin cancer worldwide. BCC represents 90-95% of all malignant eyelid tumors with lower eyelid/medial canthus lesions being more common than lower eyelid/lateral canthus lesions. Although various local flaps have been used for the reconstruction of medial canthus/adjacent eyelid defects, we find the forehead flap to be the most suited for these cases. MATERIALS AND METHODS: We are reporting a clinical series of BCC involving the medial canthus and adjacent medial lower eyelid through a retrospective review of 18 patients who underwent surgical excision of the lesion followed by primary reconstruction using forehead flaps. Patients who underwent reconstruction without forehead flaps were excluded. All cases were Saudis and underwent this type of reconstruction. Indications, results, and complications were reviewed with special emphasis on the acceptance of the obvious forehead donor site scar in Saudi patients. RESULTS: All flaps survived completely Follow up ranged from 2 to 10 years (mean of 5 years). Tumor recurrence was not seen in any of the patients. Functionally, there was no ectropion and the eyelid margin was well aligned and stable. However, epiphora was evident since lacrimal system reconstruction was not performed. CONCLUSION: We are presenting the first Saudi series of large medical canthus/lower eyelid defects that underwent reconstruction using forehead flaps. The outcome was satisfactory and there were no cases of tumor recurrence. The only disadvantage is the donor scar which seems to be acceptable in the Saudi population because of their traditional head cover. PMID- 24227991 TI - Ocular adnexal lymphoproliferative disorders in an ophthalmic referral center in Saudi Arabia. AB - PURPOSE: To study the pattern of ocular adnexal lymphoproliferative disorders (OALD) in an ophthalmic referral center in Saudi Arabia and to review their, histopathological characteristics with clinical correlation. METHODS: Retrospective chart review of 40 cases of patients who underwent incisional biopsy with the suspected diagnosis of periocular and/or adnexal lymphoid lesions over the period: 2000-2012 at the King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia. The routine histopathologic slides are reviewed by a single pathologist to identify cases of Benign Reactive Lymphoid Hyperplasia (RLH), Atypical Lymphoid Hyperplasia and probable lymphoma. The identification of the specific types of lymphoma is performed at a tertiary general hospital: King Faisal Specialist Hospital and Research Centre (KFSH&RC). RESULTS: Forty patients are included with an age range of 11-91 years and a median of 36 years. The males constitute 70% and females 30% of the cases. The right eye and/or orbit are involved in 48%. The left eye is involved in 45% while a bilateral disease is found in 7.5%. The median duration of symptoms is 5 months. The site distribution is conjunctiva (42.5%), orbit (25%), lacrimal gland (12.5%), eyelid (10%), lacrimal sac (7.5%) and caruncle (2.5%). One case is excluded after histopathologic diagnosis of malignant melanoma. Diagnosis in the remaining 39 cases includes: RLH in 14 cases (35%), atypical lymphoid hyperplasia in three cases (9%), and lymphoma in 22 cases (56%). Classification of the lymphoma group is: extranodal marginal zone lymphoma (EMZL) in 9/22 cases (41%), diffuse large B cell lymphoma (DLBCL) in 4/22 cases (18%), Castelman's disease in 3/22 cases (14%), Burkitt's lymphoma in 2/22 cases (9%), follicular lymphoma and T cell-rich B cell lymphoma: one case each (4.5%).Two cases remain unclassified. CONCLUSION: We have a wide age range which is comparable to other studies. Our results show male predominance and the commonest site of involvement is conjunctival, however if RLH cases are excluded, the commonest site for lymphoma is orbit/lacrimal gland in 45% followed by conjunctival in 23%. The commonest type of lymphoma is: EMZL in 41% followed by DLBCL in 18% then other types of lymphoma including follicular lymphoma. PMID- 24227992 TI - Dealing with hunger: Metabolic stress responses in tumors. AB - Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments. PMID- 24227993 TI - Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome and Cancer: Proceedings of the 8(th) Annual Texas Conference on Health Disparities. AB - The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education and ongoing research about health disparities both in Texas and among the national population. The 2013 Texas Conference on Health Disparities brought together experts, in research, patient care and community outreach, on the "Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Cancer". Smoking, HIV/AIDS and cancer are three individual areas of public health concern, each with its own set of disparities and risk factors based on race, ethnicity, gender, geography and socio-economic status. Disparities among patient populations, in which these issues are found to be comorbid, provide valuable information on goals for patient care. The conference consisted of three sessions addressing "Comorbidities and Treatment", "Public Health Perspectives", and "Best Practices". This article summarizes the basic science, clinical correlates and public health data presented by the speakers. PMID- 24227995 TI - Developing mobile- and BIM-based integrated visual facility maintenance management system. AB - Facility maintenance management (FMM) has become an important topic for research on the operation phase of the construction life cycle. Managing FMM effectively is extremely difficult owing to various factors and environments. One of the difficulties is the performance of 2D graphics when depicting maintenance service. Building information modeling (BIM) uses precise geometry and relevant data to support the maintenance service of facilities depicted in 3D object oriented CAD. This paper proposes a new and practical methodology with application to FMM using BIM technology. Using BIM technology, this study proposes a BIM-based facility maintenance management (BIMFMM) system for maintenance staff in the operation and maintenance phase. The BIMFMM system is then applied in selected case study of a commercial building project in Taiwan to verify the proposed methodology and demonstrate its effectiveness in FMM practice. Using the BIMFMM system, maintenance staff can access and review 3D BIM models for updating related maintenance records in a digital format. Moreover, this study presents a generic system architecture and its implementation. The combined results demonstrate that a BIMFMM-like system can be an effective visual FMM tool. PMID- 24227996 TI - Uniformity masks design method based on the shadow matrix for coating materials with different condensation characteristics. AB - An intuitionistic method is proposed to design shadow masks to achieve thickness profile control for evaporation coating processes. The proposed method is based on the concept of the shadow matrix, which is a matrix that contains coefficients that build quantitive relations between shape parameters of masks and shadow quantities of substrate directly. By using the shadow matrix, shape parameters of shadow masks could be derived simply by solving a matrix equation. Verification experiments were performed on a special case where coating materials have different condensation characteristics. By using the designed mask pair with complementary shapes, thickness uniformities of better than 98% are demonstrated for MgF2 (m = 1) and LaF3 (m = 0.5) simultaneously on a 280 mm diameter spherical substrate with the radius curvature of 200 mm. PMID- 24227994 TI - Obesity, metabolism and the microenvironment: Links to cancer. AB - Historically, cancer research has focused on identifying mutations or amplification of genes within the tumor, which informed the development of targeted therapies against affected pathways. This work often considers tumor cells in isolation; however, it is becoming increasingly apparent that the microenvironment surrounding tumor cells strongly influences tumor onset and progression. This is the so-called "seed and soil" hypothesis wherein the seed (cancer cell) is fed and molded by the metabolites, growth factors, modifications of the extracellular matrix or angiogenic factors provided by the soil (or stroma). Currently, 65% of the US population is obese or overweight; similarly staggering figures are reported in US children and globally. Obesity mediates and can exacerbate, both normal and tumor microenvironment dysfunction. Many obesity associated endocrine, metabolic and inflammatory mediators are suspected to play a role in oncogenesis by modifying systemic nutrient metabolism and the nutrient substrates available locally in the stroma. It is vitally important to understand the biological processes linking obesity and cancer to develop better intervention strategies aimed at curbing the carcinogenic events associated with obesity. In this review, obesity-driven changes in both the normal and tumor microenvironment, alterations in metabolism, and release of signaling molecules such as endocrine, growth, and inflammatory mediators will be highlighted. In addition, we will discuss the effects of the timing of obesity onset or particular "windows of susceptibility," with a focus on breast cancer etiology. PMID- 24227997 TI - Bacterial communities in polluted seabed sediments: a molecular biology assay in Leghorn Harbor. AB - Seabed sediments of commercial ports are often characterized by high pollution levels. Differences in number and distribution of bacteria in such areas can be related to distribution of pollutants in the port and to sediment conditions. In this study, the bacterial communities of five sites from Leghorn Harbor seabed were characterized, and the main bacterial groups were identified. T-RFLP was used for all samples; two 16S rRNA libraries and in silico digestion of clones were used to identify fingerprint profiles. Library data, phylogenetic analysis, and T-RFLP coupled with in silico digestion of the obtained sequences evidenced the dominance of Proteobacteria and the high percentage of Bacteroidetes in all sites. The approach highlighted similar bacterial communities between samples coming from the five sites, suggesting a modest differentiation among bacterial communities of different harbor seabed sediments and hence the capacity of bacterial communities to adapt to different levels and types of pollution. PMID- 24227998 TI - Life comparative analysis of energy consumption and CO2 emissions of different building structural frame types. AB - The objective of this research is to quantitatively measure and compare the environmental load and construction cost of different structural frame types. Construction cost also accounts for the costs of CO2 emissions of input materials. The choice of structural frame type is a major consideration in construction, as this element represents about 33% of total building construction costs. In this research, four constructed buildings were analyzed, with these having either reinforced concrete (RC) or steel (S) structures. An input-output framework analysis was used to measure energy consumption and CO2 emissions of input materials for each structural frame type. In addition, the CO2 emissions cost was measured using the trading price of CO2 emissions on the International Commodity Exchange. This research revealed that both energy consumption and CO2 emissions were, on average, 26% lower with the RC structure than with the S structure, and the construction costs (including the CO2 emissions cost) of the RC structure were about 9.8% lower, compared to the S structure. This research provides insights through which the construction industry will be able to respond to the carbon market, which is expected to continue to grow in the future. PMID- 24227999 TI - Ambient vibration testing for story stiffness estimation of a heritage timber building. AB - This paper investigates dynamic characteristics of a historic wooden structure by ambient vibration testing, presenting a novel estimation methodology of story stiffness for the purpose of vibration-based structural health monitoring. As for the ambient vibration testing, measured structural responses are analyzed by two output-only system identification methods (i.e., frequency domain decomposition and stochastic subspace identification) to estimate modal parameters. The proposed methodology of story stiffness is estimation based on an eigenvalue problem derived from a vibratory rigid body model. Using the identified natural frequencies, the eigenvalue problem is efficiently solved and uniquely yields story stiffness. It is noteworthy that application of the proposed methodology is not necessarily confined to the wooden structure exampled in the paper. PMID- 24228000 TI - Extracorporeal rescue for early and late graft failure after cardiac transplantation: short result and long-term followup. AB - OBJECTIVES: Graft failure after heart transplantation led to poor outcomes. We tried to analyze the outcomes of extracorporeal membrane oxygenation (ECMO) rescue in graft survival after transplantation. METHODS: A retrospective review of 385 consecutive heart transplants revealed 46 patients of graft failure requiring ECMO rescue (48 episodes). The pretransplant and ECMO-related variables were evaluated. RESULTS: The median age was 37.7 +/- 18.8 years, and the median support time was 155 +/- 145 hours. Success rate was 47.9% (23/48). Pretransplant ECMO use was 25% (12/48) and they had 58.3% mortality. The success rate in "early" graft failures was 51.4% (18/35) and 50% for "late" graft failure. The ischemic time with graft failure (178 +/- 70 min) was significantly longer than that without graft failure. Preoperative status and the longer ischemic time may be the major factors for failure. Long-term 5-year survival demonstrated significant survival difference between graft failure and nongraft failure. No survival difference was shown between "early" and "late" graft failure. CONCLUSIONS: Graft failure still carried high mortality if advanced circulatory support was required. Early graft failure and late graft failure had similar outcomes. Further investigation of the risk factors shows that ECMO does play a role of rescue in catastrophic conditions. PMID- 24228001 TI - Impediments for the uptake of the Botswana government's male circumcision initiative for HIV prevention. AB - Botswana remains one of the countries with high prevalence of HIV infection with a population prevalence rate of 17.6 in 2008. In 2009, the Ministry of Health launched male circumcision as an additional strategy to the already existing HIV preventive efforts. The purpose of this paper is to share what the participants of a survey to evaluate a short-term male circumcision communication strategy in seven health districts of Botswana reported as impediments for the program's uptake. Qualitative data were obtained from 32 key informants and 36 focus group discussions in 2011. Content analysis method was used to analyze data and to derive themes and subthemes. Although male circumcision was generally acceptable to communities in Botswana, the uptake of the program was slow, and participants attributed that to a number of challenges or impediments that were frustrating the initiative. The impediments were organized into sociocultural factors, knowledge/informational factors, and infrastructural and system factors. PMID- 24228002 TI - Power and time slot allocation in cognitive relay networks using particle swarm optimization. AB - The two main problems in cognitive radio networks are power and time slot allocation problems which require a precise analysis and guarantee the quality of service in both the primary and secondary users. In this paper, these two problems are considered and a method is proposed to solve the resulting optimization problem. Our proposed method provides an improved performance in solving the constrained nonlinear multiobject optimization for the power control and beamforming in order to reach the maximum capacity and proper adaption of time slots, and as a result a new scheme for joint power and time slot allocation in cognitive relay networks is proposed. We adopt space diversity access as the secondary users access scheme and divide the time between multiple secondary users according to their contribution to primary user's transmission. Helping primary users provides more opportunities for secondary users to access the channel since the primary users can release the channel sooner. In contrast, primary network leases portion of channel access time to the secondary users for their transmission using particle swarm optimization (PSO). Numerical studies show good performance of the proposed scheme with a dynamic cost function in a nonstationary environment. PMID- 24228005 TI - Micromagnetic simulations of anisotropies in coupled and uncoupled ferromagnetic nanowire systems. AB - The influence of a variation of spatial relative orientations onto the coupling dynamics and subsequent magnetic anisotropies was modeled in ferromagnetic nanowires. The wires were analyzed in the most elementary configurations, thus, arranged in pairs perpendicular to each other, leading to one-dimensional (linear) and zero-dimensional (point-like) coupling. Different distances within each elementary pair of wires and between the pairs give rise to varying interactions between parallel and perpendicular wires, respectively. Simulated coercivities show an exchange of easy and hard axes for systems with different couplings. Additionally, two of the systems exhibit a unique switching behavior which can be utilized for developing new functionalities. PMID- 24228003 TI - Effect of vasoactive intestinal peptide (VIP) on NKG2D signal pathway and its contribution to immune escape of MKN45 cells. AB - OBJECTIVE: To investigate VIP effect on the cytotoxicity of NK cell to gastric cancer cells in vitro and the relation between the effect with the NKG2D signal molecules in NK cells. MATERIAL AND METHODS: NK cells were purified from peripheral blood mononuclear cells (PBMC). Before and after NK cells were incubated with VIP or its antagonist (D-p-Cl-Phe6,Leu17)-VIP, we detected the cytotoxicity of NK cells to MKN45 gastric cancer cells by MTT and detected the expressions of NKG2D, DAP10, and NF- kappa B proteins and mRNAs in NK cells by immunocytochemistry and RT-PCR in those conditions. Then we analyzed the effect of VIP and its antagonist on the cytotocicity of NK cell to gastric cancer cells and on expressions of NKG2D, DAP10, and NF- kappa B signal molecules in NK cells. RESULTS: VIP could inhibit the cytotoxicity of NK cells to MKN45 cells and could inhibit the expressions of NKG2D, DAP10, and NF- kappa B in NK cells. However, (D p-Cl-Phe6, Leu17)-VIP could reverse those effects. CONCLUSIONS: The VIP inhibited the cytotoxicity of NK cell to MKN45 cells which might get through inhibiting the expressions of NKG2D signal molecules in NK cells. This may be one mechanism of gastric cancer cells escaping organism immune clearance. PMID- 24228006 TI - Rapid method for the determination of 5-hydroxymethylfurfural and levulinic acid using a double-wavelength UV spectroscopy. AB - This study reports on a rapid method for the determination of levulinic acid (LA) and 5-hydroxymethylfurfural (HMF) in acid hydrolyze system of glucose based on UV spectroscopy. It was found that HMF and LA have a maximum absorption at the wavelengths of 284 nm and 266 nm, respectively, in a water medium, and the absorptions of HMF and LA at 284 nm and 266 nm follow Beer's law very well. However, it was found that a major spectral interference species will arise in the quantification of HMF and LA; nonetheless, this interference can be eliminated through the absorption treatment of charcoal. Therefore, both HMF and LA can be quantified with a double-wavelength technique. The repeatability of the method had a relative standard deviation of less than 4.47% for HMF and 2.25% for LA; the limit of quantification (LOQ) was 0.017 mmol/L for HMF and 4.68 mmol/L for LA, and the recovery ranged from 88% to 116% for HMF and from 94% to 105% for LA. The present method is simple, rapid, and accurate. It is suitable to use in the research of the preparation of HMF and LA in biorefinery area. PMID- 24228007 TI - Application of a developed method for the extraction of triazines in surface waters and storage prior to analysis to seawaters of Galicia (northwest Spain). AB - A simple method based on solid-phase extraction combined with liquid chromatography for simultaneous determination of nine triazine herbicides (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine, and terbutryn) in surface water samples was developed and validated. Under optimized conditions, 50 mL of water sample was pumped through the Oasis HLB cartridge, and triazines were eluted with 3 mL acetone. Finally the extract was concentrated to dryness, reconstituted with 1 mL methanol : water (1 : 1) and injected into the HPLC-DAD system. The stability of the herbicides on the cartridges at -18 and 4 degrees C was also evaluated, and the recoveries obtained after three weeks of storage were satisfactory for all compounds. The analytical features of the proposed method were satisfactory: repeatability and intermediate precision were <10% and recoveries in spiked river water and seawater samples were higher than 93% for all compounds studied. Limits of quantification (varied from 0.46 to 0.98 ug L-1) were adequately allowing the determination of these compounds at the levels requested by the 2008/105/EC Directive. Finally, this method was applied to the analysis of 50 seawater samples from Galicia (northwest Spain). PMID- 24228008 TI - Application of HPLC with ELSD detection for the assessment of azelaic acid impurities in liposomal formulation. AB - In the course of research and development of a new pharmaceutical formulation of azelaic acid in the liposomal form, we developed a rapid and accurate method for the detection of impurities using high-performance liquid chromatography. A chromatographic column from Merck (Purospher Star RP C18, 250-4 mm (5 MUm) was used in the assay, and the mobile phase gradient consisted of three phases: A- methanol : water (5 : 95) + 1.5% (v/v) acetic acid; B--water : methanol (5 : 95) + 1.5% (v/v) acetic acid; and C--chloroform. Detection of the impurities and the active substance was performed by an evaporative light-scattering detector. The method was validated for selectivity, system precision, method precision, limit of detection, and response rates. The proposed method can be used to detect impurities in the liposomal formulation of azelaic acid. The method enables separation of azelaic acid from the identified and unidentified impurities and from the excipients used in the drug form. PMID- 24228009 TI - Soluble RAGE plasma levels in patients with coronary artery disease and peripheral artery disease. AB - The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE. PMID- 24228010 TI - Covalent grafting of the RGD-peptide onto polyetheretherketone surfaces via Schiff base formation. AB - In recent years, the synthetic polymer polyetheretherketone (PEEK) has increasingly been used in a number of orthopedic implementations, due to its excellent mechanical properties, bioinertness, and chemical resistance. For in vivo applications, the surface of PEEK, which does not naturally support cell adhesion, has to be modified to improve tissue integration. In the present work we demonstrate a novel wet-chemical modification of PEEK to modify the surface, enabling the covalent grafting of the cell-adhesive RGD-peptide. Modification of the polymer surface was achieved via Schiff base formation using an aliphatic diamine and subsequent crosslinker-mediated immobilization of the peptide. In cell culture experiments with primary osteoblasts it was shown that the RGD modified PEEK not only significantly promoted cellular adhesion but also strongly enhanced the proliferation of osteoblasts on the modified polymer surface. PMID- 24228011 TI - Association between waste management and HBV among solid municipal waste workers: a systematic review and meta-analysis of observational studies. AB - AIM: To conduct a systematic review of this relationship using available published observational studies in the field of solid municipal waste treatment. METHODS: The review of the scientific literature was based on Medline and Scopus databases up to December 2012, using the keywords HBV, waste, solid, treatment, workers, disposal, and refuse in different combinations. RESULTS: 160 studies were found and checked. Finally, 5 observational studies were considered suitable, all cross-sectional. The pooled proportion of HBs-Ag considering all the studies was 11% (95% CI: 5-21%), and considering the high quality studies only, this proportion was 14% (95% CI: 6-24%). The pooled proportion of HBs-Ab positivity among waste workers considering all the studies was 14.2% (95% CI: 1.4 37.2%), and considering the high quality studies only, this proportion was 24% (95% CI: 18-30%). The pooled proportion of HBc-Ab positivity among waste workers considering all the studies was 24% (95% CI: 6-49%). The pooled estimation of the risk of HBV positivity (HBsAg) among exposed was OR = 2.39 (95% CI: 0.88-6.52). CONCLUSION: In conclusion, waste workers need to be vaccinated against HBV infection since they are at risk of acquiring this infection through the exposure to potentially infected waste. PMID- 24228012 TI - Prognosis of elderly Japanese patients aged >=80 years undergoing hemodialysis. AB - Although the number of elderly patients requiring dialysis has increased, data regarding the prognosis of elderly patients undergoing hemodialysis are limited. In the present study, prognosis in Japanese hemodialysis patients aged >=80 years was evaluated. From January 1988 to July 2013, 1144 consecutive patients with end stage renal disease required renal replacement therapy at our institution; of these, 141 were aged >=80 years. These patients' charts were retrospectively reviewed for relevant clinical variables and survival time. The life expectancies table from the National Vital Statistics database was used, and prognostic factors were assessed by multivariate analysis. In total, 107 deaths (76%) were recorded during the study period. The median survival time and estimated life shortening period in the patients were 2.6 years and -5.3 years, respectively. Eastern Cooperative Oncology Group Performance Status and hemoglobin level were revealed as prognostic factors in the multivariate analysis. Estimates of prognosis and prognostic factors may provide useful information for physicians as well as elderly patients with end-stage kidney disease. PMID- 24228013 TI - Maternal hypotension during fetoscopic surgery: incidence and its impact on fetal survival outcomes. AB - In this retrospective cohort study, we aimed to determine the incidence of intraoperative maternal hypotension during fetoscopic surgery for twin-twin transfusion syndrome (TTTS) and to evaluate the impact of intraoperative hypotension on fetal survival. A total of 328 TTTS patients with recipient twin cardiomyopathy who underwent fetoscopic surgery under epidural anesthesia were included. The exposure of interest was maternal medical therapy with nifedipine for the treatment of fetal cardiomyopathy. We found that intraoperative hypotension occurred in 53.4% (175/328 patients). There was no statistically significant difference in incidence of hypotension between nifedipine exposure and nonexposure groups (54.8% versus 50.8%, P = 0.479). However, the nifedipine exposure group received a statistically significant higher dose of phenylephrine (7.04 +/- 6.38 mcg/kg versus 4.70 +/- 4.14 mcg/kg, P = 0.018) and higher doses of other vasopressor, as counted by number of treatments (6.06 +/- 4.58 versus 4.96 +/- 3.42, P = 0.022). There were no statistically significant differences in acute fetal survival rate (within 5 days) and fetal survival rate at birth between hypotensive and nonhypotensive patients. We concluded that preoperative exposure to nifedipine resulted in increased intraoperative maternal vasopressor requirement during fetoscopic surgery under epidural anesthesia. In patients who had intraoperative maternal hypotension, there was no correlation between the presence of maternal hypotension and postoperative fetal survival. PMID- 24228014 TI - Evaluation of self-etching adhesive and Er:YAG laser conditioning on the shear bond strength of orthodontic brackets. AB - The purpose of this study was to evaluate the shear bond strength, the adhesive remnant index scores, and etch surface of teeth prepared for orthodontic bracket bonding with self-etching primer and Er:YAG laser conditioning. One hundred and twenty bovine incisors were randomly divided into four groups. In Group I (Control), the teeth were conditioned with 35% phosphoric acid for 15 seconds. In Group II the teeth were conditioned with Transbond Plus SEP (5 sec); III and IV were irradiated with the Er:YAG 150 mJ (11.0 J/cm2), 150 mJ (19.1 J/cm2), respectively, at 7-12 Hz with water spray. After surface preparation, upper central incisor stainless steel brackets were bonded with Transbond Plus Color Change Adhesive. The teeth were stored in water at 37 degrees C for 24 hours and shear bond strengths were measured, and adhesive remnant index (ARI) was determined. The conditioned surface was observed under a scanning electron microscope. One-way ANOVA and chi-square test were used. Group I showed the significantly highest values of bond strength with a mean value of 8.2 megapascals (MPa). The lesser amount of adhesive remnant was found in Group III. The results of this study suggest that Er:YAG laser irradiation could not be an option for enamel conditioning. PMID- 24228015 TI - Cardiac safety of diclofenac at a single dose in ram. AB - Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5 mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), and muscular (creatine kinase) damage markers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep. PMID- 24228016 TI - Lateral condyle fracture of the humerus in children treated with bioabsorbable materials. AB - The aim of this study was to compare clinical and radiological outcome of lateral condyle fracture of the elbow in children treated with bioabsorbable or metallic material. From January 2008 to December 2009, 16 children with similar fractures and ages were grouped according to the fixation material used. Children were seen at 3, 6, and 12 months and more than 4 years (mean 51.8 months) postoperatively. The clinical results were compared using the Mayo Elbow Performance Score (MEPS). Radiographic studies of the fractured and opposite elbow were assessed at last follow-up control. Twelve children had a sufficient followup and could be included in the study. Seven could be included in the traditional group and 5 in the bioabsorbable group. At 12 months, the MEPS was 100 for every child in both groups. Asymptomatic bony radiolucent visible tracks and heterotopic ossifications were noted in both groups. There were no significant differences in terms of clinical and radiological outcome between the two groups. The use of bioabsorbable pins or screws is a reasonable alternative to the traditional use of metallic materials for the treatment of lateral condyle fracture of the elbow in children. PMID- 24228017 TI - Is %DeltaSUVmax a useful indicator of survival in patients with advanced nonsmall cell lung cancer? AB - PURPOSE: To investigate the impact of the maximum standardized uptake value (SUVmax), size of primary lung lesion, and %DeltaSUVmax on outcome (overall survival (OS) and 2-year disease-free survival (2-year DFS)) of patients with advanced nonsmall-cell lung cancer (NSCLC). MATERIALS AND METHODS: 86 stage III IV NSCLC patients underwent 18 F-FDGPET/CT, before and after chemotherapy, and were classified into subgroups according to the response criteria of the European Organization for Research and Treatment of Cancer. SUVmax values and tumor size with the best prognostic significance were searched. Correlation between the SUVmax value and the initial response to therapy (best response) and the relationship between %DeltaSUVmax and OS were assessed. RESULTS: In patients in PD (20/86), the average pretreatment SUVmax was 11.8 +/- 5.23, and the mean size of the primary lesion was 43.35 mm +/- 16.63. In SD, PR, and CR patients (66/86), the average pretreatment SUVmax was 12.7 +/- 8.05, and the mean size of the primary lesion was 41.6 mm +/- 21.15. Correlation was identified only for %DeltaSUVmax; patients with PD (DeltaSUVmax > +25%) showed a worse OS than patients with DeltaSUVmax < +25% (CR, PR, and SD) (P = 0.0235). CONCLUSIONS: In stage III-IV NSCLC, among the assessed factors, only %DeltaSUVmax may be considered as a useful prognostic factor. PMID- 24228019 TI - Extending stochastic network calculus to loss analysis. AB - Loss is an important parameter of Quality of Service (QoS). Though stochastic network calculus is a very useful tool for performance evaluation of computer networks, existing studies on stochastic service guarantees mainly focused on the delay and backlog. Some efforts have been made to analyse loss by deterministic network calculus, but there are few results to extend stochastic network calculus for loss analysis. In this paper, we introduce a new parameter named loss factor into stochastic network calculus and then derive the loss bound through the existing arrival curve and service curve via this parameter. We then prove that our result is suitable for the networks with multiple input flows. Simulations show the impact of buffer size, arrival traffic, and service on the loss factor. PMID- 24228020 TI - A TaqMan real-time PCR assay for detection and quantification of Sporisorium scitamineum in sugarcane. AB - Sporisorium scitamineum is a fungal smut pathogen epidemic in sugarcane producing areas. Early detection and proper identification of the smut are an essential requirement in its management practice. In this study, we developed a TaqMan real time PCR assay using specific primers (bEQ-F/bEQ-R) and a TaqMan probe (bEQ-P) which were designed based on the bE (b East mating type) gene (Genbank Accession no. U61290.1). This method was more sensitive (a detection limit of 10 ag pbE DNA and 0.8 ng sugarcane genomic DNA) than that of conventional PCR (10 fg and 100 ng, resp.). Reliability was demonstrated through the positive detection of samples collected from artificially inoculated sugarcane plantlets (FN40). This assay was capable of detecting the smut pathogen at the initial stage (12 h) of infection and suitable for inspection of sugarcane pathogen-free seed cane and seedlings. Furthermore, quantification of pathogen was verified in pathogen challenged buds in different sugarcane genotypes, which suggested its feasibility for evaluation of smut resistance in different sugarcane genotypes. Taken together, this novel assay can be used as a diagnostic tool for sensitive, accurate, fast, and quantitative detection of the smut pathogen especially for asymptomatic seed cane or plants and evaluation of smut resistance of sugarcane genotypes. PMID- 24228021 TI - The research on borehole stability in depleted reservoir and caprock: using the geophysics logging data. AB - Long-term oil and gas exploitation in reservoir will lead to pore pressure depletion. The pore pressure depletion will result in changes of horizontal in situ stresses both in reservoirs and caprock formations. Using the geophysics logging data, the magnitude and orientation changes of horizontal stresses in caprock and reservoir are studied. Furthermore, the borehole stability can be affected by in-situ stresses changes. To address this issue, the dehydration from caprock to reservoir and roof effect of caprock are performed. Based on that, the influence scope and magnitude of horizontal stresses reduction in caprock above the depleted reservoirs are estimated. The effects of development on borehole stability in both reservoir and caprock are studied step by step with the above geomechanical model. PMID- 24228022 TI - Cardiovascular risk assessment: a comparison of the Framingham, PROCAM, and DAD equations in HIV-infected persons. AB - This study aims to estimate the risk of cardiovascular disease (CVD) and to assess the agreement between the Framingham, Framingham with aggravating factors, PROCAM, and DAD equations in HIV-infected patients. A cross-sectional study was conducted in an outpatient centre in Brazil. 294 patients older than 19 years were enrolled. Estimates of 10-year cardiovascular risk were calculated. The agreement between the CVD risk equations was assessed using Cohen's kappa coefficient. The participants' mean age was 36.8 years (SD = 10.3), 76.9% were men, and 66.3% were on antiretroviral therapy. 47.8% of the participants had abdominal obesity, 23.1% were current smokers, 20.0% had hypertension, and 2.0% had diabetes. At least one lipid abnormality was detected in 72.8%, and a low HDL C level was the most common. The majority were classified as having low risk for CV events. The percentage of patients at high risk ranged from 0.4 to 5.7. The PROCAM score placed the lowest proportion of the patients into a high-risk group, and the Framingham equation with aggravating factors placed the highest proportion of patients into the high-risk group. Data concerning the comparability of different tools are informative for estimating the risk of CVD, but accuracy of the outcome predictions should also be considered. PMID- 24228023 TI - Immunomics in Skin Cancer - Improvement in Diagnosis, Prognosis and Therapy Monitoring. AB - This review will focus on the elements of the skin's immune system, immune cells and/or non-immune cells that support immune mechanisms, molecules with immune origin and/or immune functions that are involved in skin carcinogenesis. All these immune elements are compulsory in the development of skin tumors and/or sustainability of the neoplastic process. In this light, recent data gathered in this review will acknowledge all immune elements that contribute to skin tumorigenesis; moreover, they can serve as immune biomarkers. These immune markers can contribute to the diagnostic improvement, prognosis forecast, therapy monitoring, and even personalized therapeutical approach in skin cancer. Immune processes that sustain tumorigenesis in non-melanoma and melanoma skin cancers are described in the framework of recent data. PMID- 24228025 TI - Significance of glutathione peroxidase 1 and caudal-related homeodomain transcription factor in human gastric adenocarcinoma. AB - Aim. To investigate the expressions of glutathione peroxidase 1 (GPX1) and caudal related homeodomain transcription factor (CDX2) in GAC and their correlation with clinicopathological features and tumor cell proliferation. Methods. The expressions of GPX1, CDX2, and Ki67 were immunohistochemically evaluated in 172 GAC specimens. The association of GPX1 and CDX2 with patient's clinicopathological features and Ki67 positive rate was analyzed statistically. Results. In 172 cases of GAC, the expression of GPX1 was weaker than that in adjacent normal mucosa, and the expression of CDX2 was higher than that in adjacent normal mucosa. High expression GPX1 strong-expression was associated with differentiation, Lauren type, WHO type and extensive lymph node metastasis of GAC. High expression of CDX2 was associated with differentiation, Lauren type, WHO type, extensive lymph node metastasis, and TNM of GAC. Survival curves showed that expressions of GPX1 and CDX2 were factors of good outcome (P = .03 and .02, resp.). According to multivariate analysis, only lymph node metastasis, TNM stage, and CDX2 expression were independently associated with survival. In addition, a strong association of GPX1 expression was noted with Ki67 and CDX2. Conclusions. The expression of GPX1 and CDX2 may play a role in the carcinogenesis, differentiation, and progression of GAC, and CDX2 may be an independent prognostic factor. PMID- 24228026 TI - Risk of Atherosclerosis and Helicobacter pylori Infection according to CD14 Promotor Polymorphism in Healthy Korean Population. AB - Background and Aim. We aim to elucidate the association of risk factors for atherosclerosis and H. pylori infection according to the promotor polymorphism of the CD14 gene in healthy Korean population. Methods. The patients who visited our hospital for routine health examinations and 266 healthy adults (170 males and 96 females) were enrolled in this study. The promotor polymorphism at -159C/T of the CD14 gene was determined by PCR-restriction fragment length polymorphism analysis. According to genetic polymorphism and H. pylori infection, we analyzed the risk of atherosclerosis. Results. The genotype frequencies were CC 7.9%, CT 45.1%, and TT 47.0%, respectively. There were no differences between specific genotypes of CD14 gene and H. pylori infection rate. As for HDL cholesterol level, there were significant differences among the three genotypes (P < 0.01). In subjects with H. pylori infection, no significant differences were observed between specific genotypes of CD14 gene and the risk factors of atherosclerosis. Conclusion. The promotor polymorphism at -159C/T of the CD14 gene was associated with the risk factor of atherosclerosis in healthy Korean population. However, it was not associated with the rate of H. pylori infection and H. pylori induced atherosclerotic risk. PMID- 24228024 TI - Anti-cancer Therapies in High Grade Gliomas. AB - High grade gliomas represent one of the most aggressive and treatment-resistant types of human cancer, with only 1-2 years median survival rate for patients with grade IV glioma. The treatment of glioblastoma is a considerable therapeutic challenge; combination therapy targeting multiple pathways is becoming a fast growing area of research. This review offers an up-to-date perspective of the literature about current molecular therapy targets in high grade glioma, that include angiogenic signals, tyrosine kinase receptors, nodal signaling proteins and cancer stem cells related approaches. Simultaneous identification of proteomic signatures could provide biomarker panels for diagnostic and personalized treatment of different subsets of glioblastoma. Personalized medicine is starting to gain importance in clinical care, already having recorded a series of successes in several types of cancer; nonetheless, in brain tumors it is still at an early stage. PMID- 24228027 TI - The Effects of Eucheuma cottonii on Signaling Pathway Inducing Mucin Synthesis in Rat Lungs Chronically Exposed to Particulate Matter 10 (PM10) Coal Dust. AB - This study was aimed at investigating the effects of Eucheuma cottonii (EC) in oxidative stress and the signaling for mucin synthesis in rat lungs chronically exposed to coal dust. Coal dust with concomitant oral administration of ethanolic extract of EC at doses of 150 (EC150) or 300 mg/kg BW (EC300) compared to exposed to PM10 coal dust at doses of 6.25 (CD6.25), 12.5 (CD12.5), or 25 mg/m(3) (CD25) (an hour daily for 6 months) and nonexposure group (control). The malondialdehyde (MDA), epidermal growth factor (EGF), transforming growth factor (TGF)- alpha , epidermal growth factor receptor (EGFR), and MUC5AC levels were determined in the lung. The administration of EC300 significantly (p < 0.05) reduced the MDA levels in groups exposed to all doses of coal dust compared to the respective coal dust exposed nonsupplemented groups. Although not statistically significant,EC reduced the EGF levels and EGFR expressions in CD12.5 and CD25 groups and decreased the TGF- alpha , level and MUC5AC expression in CD25 group compared to the respective coal dust-exposed nonsupplemented groups. EC was able to decrease oxidative stress and was also able to decrease signaling for mucin synthesis, at least a part, via reducing the ligand in chronic coal dust exposure. PMID- 24228029 TI - Idiopathic hirsutism and insulin resistance. AB - Background and Objectives. Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (HI) are the two most common causes of hirsutism. Insulin resistance plays a key role in PCOS, but there are not enough data showing that patients with HI also have insulin resistance. This study was designed to evaluate the presence of insulin resistance in women with HI. Methods. Based on a cross sectional study, two groups of age-BMI matched, hirsute women were compared to age-BMI matched, nonhirsute women. Sixty nonobese women with PCOS, thirty nonobese women with HI, and sixty nonobese control women were included in the study. Samples of hormones including androgens were measured. Insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) was compared between three groups by the Kruskal-Wallis test. Results. Patients with PCOS had significantly higher basal insulin level (16.04 +/- 1.4 versus 7.32 +/- 6.85 MU Iu/mL) and HOMA-IR score (3.7 +/- 3.36 versus 1.75 +/- 1.67) than patients with HI (P 0.001). Patients with HI also had significantly higher basal insulin level and HOMA-IR score than control group (P 0.001). Conclusion. Our data suggest that both PCOS and HI are associated with insulin resistance and these patients are more insulin resistant than healthy control people. PMID- 24228030 TI - An Evaluation of Growth Hormone and IGF-1 Responses in Neonates with Hyperinsulinaemic Hypoglycaemia. AB - Background. Hyperinsulinaemic Hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycemia in the neonatal period. It has been shown that the neonates with HH fail to generate adequate serum cortisol counterregulatory response to symptomatic hypoglycemia. However the role played by growth hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) is not clear. Objectives. To compare the serum GH, IGF-1, and IGFBP3 responses to HH in neonates undergoing diagnostic fasting studies. Population and Methods. Data was retrospectively collected on full-term neonates who presented with severe and persistent hypoglycemia and were confirmed to have HH. Neonates born with intrauterine growth retardation or those on medical therapy (diazoxide or octreotide) were excluded. Results. 31 neonates with HH (mean gestational age: 38 weeks and mean birth weight: 3.9 kg) were included in the study. The mean age at the time of diagnostic fast was 4 weeks, the mean glucose concentration during the fast was 2.2 mmol/L (SEM +/- 0.09), and the mean insulin level was 11.9 mU/L (+/-2.12). The mean serum GH concentration during the hypoglycaemia was 12.5 ug/L (+/-1.53). The mean serum IGF-1 and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) levels were 29.2 ng/ml (+/-7.8) and 1.21 mg/L (+/-0.13), respectively. The mean cortisol concentration was 201 nmol/L (+/-33). Conclusions. Whilst the serum IGF 1 and IGFBP3 levels are relatively low during hypoglycaemia, the serum GH level does reflect an appropriate counterregulatory response to HH. The serum cortisol counterregulatory hormonal responses are blunted. Further studies are required to understand the mechanism(s) of these hormonal alterations in neonates with HH. PMID- 24228031 TI - Three-dimensional reconstruction of oral tongue squamous cell carcinoma at invasion front. AB - We conducted three-dimensional (3D) reconstruction of oral tongue squamous cell carcinoma (OTSCC) using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter) was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4 MU m thick) were double immunostained with pan-cytokeratin and Ki67 antibodies and digitized images were acquired using virtual microscopy. For 3D reconstruction, image registration and RGB color segmentation were automated using ImageJ software to avoid operator-dependent subjective errors. Based on the 3D tumor architecture, we classified the mode of invasion into four types: pushing and bulky architecture; trabecular architecture; diffuse spreading; and special forms. Direct visualization and quantitative assessment of the parenchymal-stromal border provide a new dimension in our understanding of OTSCC architecture. These 3D morphometric analyses also ascertained that cell invasion (individually and collectively) occurs at the deep invasive front of the OTSCC. These results demonstrate the advantages of histology-based 3D reconstruction for evaluating tumor architecture and its potential for a wide range of applications. PMID- 24228028 TI - The Endocannabinoid System in the Postimplantation Period: A Role during Decidualization and Placentation. AB - Although the detrimental effects of cannabis consumption during gestation are known for years, the vast majority of studies established a link between cannabis consumption and foetal development. The complex maternal-foetal interrelationships within the placental bed are essential for normal pregnancy, and decidua definitively contributes to the success of this process. Nevertheless, the molecular signalling network that coordinates strategies for successful decidualization and placentation are not well understood. The discovery of the endocannabinoid system highlighted new signalling mediators in various physiological processes, including reproduction. It is known that endocannabinoids present regulatory functions during blastocyst development, oviductal transport, and implantation. In addition, all the endocannabinoid machinery was found to be expressed in decidual and placental tissues. Additionally, endocannabinoid's plasmatic levels were found to fluctuate during normal gestation and to induce decidual cell death and disturb normal placental development. Moreover, aberrant endocannabinoid signalling during the period of placental development has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the endocannabinoid system in these critical processes is explored and discussed. PMID- 24228032 TI - Chapter Oral Health Advocates: A Nationwide Model for Pediatrician Peer Education and Advocacy about Oral Health. AB - Objective. (1) To describe an innovative program training US pediatricians to be Chapter Oral Health Advocates (COHAs). (2) To provide insight into COHAs' experiences disseminating oral health knowledge to fellow pediatricians. Patients and Methods. Interviews with 40 COHAs who responded to an email request, from a total of 64 (62% response). Transcripts were analyzed for common themes about COHA activities, facilitators, and barriers. Results. COHAs reported positive experiences at the AAP oral health training program. A subset of academic COHAs focused on legislative activity and another on resident education about oral health. Residents had an easier time adopting oral health activities while practicing pediatricians cited time constraints. COHAs provided insights into policy, barriers, and facilitators for incorporating oral health into practice. Conclusions. This report identifies factors influencing pediatricians' adoption of oral health care into practice. COHAs reported successes in training peers on integrating oral health into pediatric practice, identified opportunities and challenges to oral health implementation in primary care, and reported issues about the state of children's oral health in their communities. With ongoing support, the COHA program has a potential to improve access to preventive oral health services in the Medical Home and to increase referrals to a Dental Home. PMID- 24228033 TI - Immunohistochemical Analysis of the Activation Status of the Akt/mTOR/pS6 Signaling Pathway in Oral Lichen Planus. AB - Introduction. Aberrations of the Akt/mTOR/pS6 pathway have been linked to various types of human cancer, including oral squamous cell carcinoma (OSCC). The purpose of this study was to evaluate the activation status of Akt, mTOR, and pS6 in oral lichen planus (OLP) in comparison with oral premalignant and malignant lesions and normal oral mucosa (NM). Materials and Methods. Immunohistochemistry for p Akt, p-mTOR, and phospho-pS6 was performed in 40 OLP, 20 oral leukoplakias (OL), 10 OSCC, and 10 control samples of NM. Results. Nuclear p-Akt expression was detected in the vast majority of cases in all categories, being significantly higher in OL. Cytoplasmic p-Akt and p-mTOR staining was present only in a minority of OLP cases, being significantly lower compared to OL and OSCC. Phospho pS6 showed cytoplasmic positivity in most OLP cases, which however was significantly lower compared to OL and OSCC. Conclusions. Overall, cytoplasmic p Akt, p-mTOR, and phospho-pS6 levels appear to be significantly lower in OLP compared to OL and OSCC. However, the expression of these molecules in a subset of OLP cases suggests that activation of Akt/mTOR/pS6 may occur in the context of OLP, possibly contributing to the premalignant potential of individual cases. PMID- 24228034 TI - The role of hypoxia in orthodontic tooth movement. AB - Orthodontic forces are known to have various effects on the alveolar process, such as cell deformation, inflammation, and circulatory disturbances. Each of these conditions affecting cell differentiation, cell repair, and cell migration, is driven by numerous molecular and inflammatory mediators. As a result, bone remodeling is induced, facilitating orthodontic tooth movement. However, orthodontic forces not only have cellular effects but also induce vascular changes. Orthodontic forces are known to occlude periodontal ligament vessels on the pressure side of the dental root, decreasing the blood perfusion of the tissue. This condition is accompanied by hypoxia, which is known to either affect cell proliferation or induce apoptosis, depending on the oxygen gradient. Because upregulated tissue proliferation rates are often accompanied by angiogenesis, hypoxia may be assumed to fundamentally contribute to bone remodeling processes during orthodontic treatment. PMID- 24228036 TI - A sharpened focus on patient-centred care / Focalisation accrue sur les soins axes sur le patient. PMID- 24228035 TI - Different Culture Media Affect Proliferation, Surface Epitope Expression, and Differentiation of Ovine MSC. AB - Orthopedic implants including engineered bone tissue are commonly tested in sheep. To avoid rejection of heterologous or xenogeneic cells, autologous cells are preferably used, that is, ovine mesenchymal stem cells (oMSC). Unlike human MSC, ovine MSC are not well studied regarding isolation, expansion, and characterization. Here we investigated the impact of culture media composition on growth characteristics, differentiation, and surface antigen expression of oMSC. The culture media varied in fetal calf serum (FCS) content and in the addition of supplements and/or additional epidermal growth factor (EGF). We found that FCS strongly influenced oMSC proliferation and that specific combinations of supplemental factors (MCDB-201, ITS-plus, dexamethasone, and L-ascorbic acid) determined the expression of surface epitopes. We compared two published protocols for oMSC differentiation towards the osteogenic, adipogenic, and chondrogenic fate and found (i) considerable donor to donor variations, (ii) protocol-dependent variations, and (iii) variations resulting from the preculture medium composition. Our results indicate that the isolation and culture of oMSC in different growth media are highly variable regarding oMSC phenotype and behaviour. Furthermore, variations from donor to donor critically influence growth rate, surface marker expression, and differentiation. PMID- 24228037 TI - Patient-centred care. PMID- 24228038 TI - Ontario pharmacists concerned about federal oversight of imported medications in light of birth-control pill recalls. PMID- 24228039 TI - Newfoundland and Labrador government needs to catch up to the rest of the country in pharmacist authority. PMID- 24228040 TI - Manitoba pharmacists pass new regulations for expanded scope of practice envisioned 7 years ago. PMID- 24228041 TI - Expanded authority for Quebec pharmacists delayed in wake of ongoing negotiations on compensation. PMID- 24228042 TI - Arthritis screening and support program to be delivered by pharmacists at Shoppers Drug Mart. PMID- 24228043 TI - Public health watch. PMID- 24228044 TI - On becoming a new pharmacist. PMID- 24228045 TI - Cancer's ability to target your health and your wallet. PMID- 24228046 TI - Pharmacy's role in a modern health continuum. PMID- 24228047 TI - Real-world application of MedsCheck opportunities: The Costco pharmacists intervention trial for reduction of cardiovascular risk. PMID- 24228048 TI - Ontario Pharmaceutical Opinion Program: Initial experience. PMID- 24228049 TI - Reducing fall risk while managing pain and insomnia: Addressing polypharmacy in an 81-year-old woman. PMID- 24228050 TI - Guidelines for pharmacists integrating into primary care teams. PMID- 24228051 TI - Publicly funded remuneration for the administration of injections by pharmacists: An international review. AB - BACKGROUND: The administration of injections has become an increasingly common addition to pharmacists' scope of practice. Four Canadian provinces, all US states and a number of other countries have regulations allowing pharmacists to administer injections. However, the extent to which such services are remunerated is unknown. METHODS: We contacted regulatory and advocacy organizations within those jurisdictions where pharmacists are authorized to administer injections to identify publicly funded programs that pay pharmacists for these services, as well as details of the eligible drugs/vaccines. Patient or private insurer payment programs were excluded. RESULTS: Of the 281 organizations we contact-ed, 104 provided information on a total of 34 pharmacist vaccination programs throughout Canada, the United States, England, Wales and Ireland. Converted to 2013 Canadian dollars, remuneration averages $13.12 (SD $4.63) per injection (range, $4.14-$21.21). All regions allow pharmacists to bill for administration of the influenza vaccine, while some states allow for a number of other vaccines. Alberta has the broadest range of injections eligible for remuneration. DISCUSSION: Despite evidence of increased vaccination rates in areas allowing pharmacist administration of injections, the availability of publicly funded remuneration programs and the fee offered vary by more than 5-fold across North America and the United Kingdom. CONCLUSION: Pharmacist-administered injections have great public health potential. The range of injections eligible for remuneration should be expanded to include a wide range of vaccines and other injectable drugs, and remuneration should be sufficient to encourage more pharmacists to provide this service. PMID- 24228052 TI - Expanded pharmacy practice: Where are we, and where do we need to go? PMID- 24228053 TI - Special CPJ Supplement: CPhA 2013 Abstracts, Posters and Presentations. PMID- 24228055 TI - Indoor volatile organic compounds and chemical sensitivity reactions. AB - Studies of unexplained symptoms observed in chemically sensitive subjects have increased the awareness of the relationship between neurological and immunological diseases due to exposure to volatile organic compounds (VOCs). However, there is no direct evidence that links exposure to low doses of VOCs and neurological and immunological dysfunction. We review animal model data to clarify the role of VOCs in neuroimmune interactions and discuss our recent studies that show a relationship between chronic exposure of C3H mice to low levels of formaldehyde and the induction of neural and immune dysfunction. We also consider the possible mechanisms by which VOC exposure can induce the symptoms presenting in patients with a multiple chemical sensitivity. PMID- 24228056 TI - The "hidden diversity" of medicinal plants in northeastern Brazil: diagnosis and prospects for conservation and biological prospecting. AB - Increases in ethnobotanical studies and knowledge in recent decades have led to a greater and more accurate interpretation of the overall patterns related to the use of medicinal plants, allowing for a clear identification of some ecological and cultural phenomena. "Hidden diversity" of medicinal plants refers in the present study to the existence of several species of medicinal plants known by the same vernacular name in a given region. Although this phenomenon has previously been observed in a localized and sporadic manner, its full dimensions have not yet been established. In the present study, we sought to assess the hidden diversity of medicinal plants in northeastern Brazil based on the ethnospecies catalogued by local studies. The results indicate that there are an average of at least 2.78 different species per cataloged ethnospecies in the region. Phylogenetic proximity and its attendant morphological similarity favor the interchangeable use of these species, resulting in serious ecological and sanitary implications as well as a wide range of options for conservation and bioprospecting. PMID- 24228057 TI - Electroacupuncture Ameliorates Learning and Memory via Activation of the CREB Signaling Pathway in the Hippocampus to Attenuate Apoptosis after Cerebral Hypoperfusion. AB - Studies have shown that electroacupuncture (EA) ameliorates learning and memory after ischemic injury. However, there have been few studies elucidating the mechanisms of EA on learning and memory in cerebral hypoperfusion. In this study, we explored the cAMP response element-binding protein (CREB) signaling pathway mediated antiapoptotic action involved in EA-induced improvement of learning and memory. EA at GV20 and GV14 acupoints was applied in cerebral hypoperfusion rats. A Morris water maze task was performed, and the immunoreactivities of pCREB, Bcl 2, and Bax in the hippocampal CA1 area were evaluated by the Western blotting technique. Our findings indicated that (1) EA ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; (2) EA increased the immunoreactivities of pCREB and Bcl-2 and decreased the immunoreactivity of Bax; (3) intracerebroventricular administration of H89 (the inhibitor of protein kinase A) blocked EA-induced, pCREB-mediated antiapoptotic action and improved learning and memory. These results suggest that EA can ameliorate learning and memory via activation of the CREB signaling pathway in the hippocampus to attenuate apoptosis after cerebral hypoperfusion. PMID- 24228058 TI - Ethanol Extract of Ulmus pumila Root Bark Inhibits Clinically Isolated Antibiotic Resistant Bacteria. AB - In this study, root bark of Ulmus pumila (U. pumila) was extracted with ethanol, and then the antimicrobial effects were tested on clinically isolated 12 MRSA strains and 1 standard MRSA strain. U. pumila showed antibacterial activities against all MRSA strains. Minimum inhibitory concentration (MIC) of U. pumila root bark against all MRSA strains revealed a range from 125 to 250 MU g/mL. These results may provide the scientific basis on which U. pumila root bark has traditionally been used against infectious diseases in Korea. In real-time PCR analysis, the sub-MIC (64-125 MU g/mL) concentrations of U. pumila root bark extract showed the inhibition of the genetic expressions of virulence factors such as mecA, sea, agrA, and sarA in standard MRSA. Phytochemical analyses of U. pumila root bark showed relatively strong presence of phenolics, steroids, and terpenoids. These results suggest that the ethanol extract of U. pumila root bark may have antibacterial activity against MRSA, which may be related to the phytochemicals such as phenolics, steroids, and terpenoids. Further studies are needed to determine the active constituents of U. pumila root bark responsible for such biomolecular activities. PMID- 24228054 TI - Evidence for prion-like mechanisms in several neurodegenerative diseases: potential implications for immunotherapy. AB - Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases. While the impact of TSEs on human health is relatively minor, these diseases are having a major influence on how we view, and potentially treat, other more common neurodegenerative disorders. Until recently, TSEs encapsulated a distinct category of neurodegenerative disorder, exclusive in their defining characteristic of infectivity. It now appears that similar mechanisms of self-propagation may underlie other proteinopathies such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. This link is of scientific interest and potential therapeutic importance as this route of self-propagation offers conceptual support and guidance for vaccine development efforts. Specifically, the existence of a pathological, self-promoting isoform offers a rational vaccine target. Here, we review the evidence of prion-like mechanisms within a number of common neurodegenerative disorders and speculate on potential implications and opportunities for vaccine development. PMID- 24228059 TI - The effect of electroacupuncture on osteosarcoma tumor growth and metastasis: analysis of different treatment regimens. AB - Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM) approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA) regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3) beginning at postimplantation day 3 (PID 3). Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7), starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA's potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation. PMID- 24228060 TI - Use of laser-induced breakdown spectroscopy for the detection of glycemic elements in Indian medicinal plants. AB - The demand for interdisciplinary research is increasing in the new millennium to help us understand complex problems and find solutions by integrating the knowledge from different disciplines. The present review is an excellent example of this and shows how unique combination of physics, chemistry, and biological techniques can be used for the evaluation of Indian medicinal herbs used for treating diabetes mellitus. Laser-induced breakdown spectroscopy (LIBS) is a sensitive optical technique that is widely used for its simplicity and versatility. This review presents the most recent application of LIBS for detection of glycemic elements in medicinal plants. The characteristics of matrices, object analysis, use of laser system, and analytical performances with respect to Indian herbs are discussed. PMID- 24228061 TI - Overview of Botanical Status in EU, USA, and Thailand. AB - The botanical status in EU, USA, and Thailand is different owing to the regulatory status, the progress of science, and the influence of culture and society. In the EU, botanicals are positioned as herbal medicinal products and food supplements, in the US they are regulated as dietary supplements but often used as traditional medicines, and in Thailand, they are regulated and used as traditional medicines. Information for some of the most popular botanicals from each country is included in this review. PMID- 24228062 TI - Does Oral Ingestion of Piper sarmentosum Cause Toxicity in Experimental Animals? AB - The prevalence of diabetes mellitus has reached epidemic proportion in Malaysia and worldwide. Scientific studies have shown that herbal plant Piper sarmentosum exhibits an antidiabetic property. Despite the extensive usage and studies of this herb as alternative medicine, there is paucity of the literature on the safety information of this plant. Thus, the present study aimed to observe the subacute toxic effects of Piper sarmentosum aqueous extract (PSAE) on the haematological profile, liver, and kidney in rats. The extract was administered by oral gavage to 6 male and female Sprague Dawley rats in daily dose of 50 mg/kg, 300 mg/kg, and 2000 mg/kg for 28 consecutive days. The control group received normal saline. General behavior of the rats, adverse effects, and mortality were observed for 28 days. The haematological and biochemical parameters were determined at baseline and after the treatment. PSAE did not show abnormality on the body weight and gross observation of internal organs. The haematological, biochemical and histopathological profiles showed minimal changes and variation within normal clinical range except for significant increase in serum potassium level that suggests the need of regular monitoring. Nevertheless, these findings suggested that PSAE up to 2000 mg/kg/day did not show subacute toxicity in Sprague Dawley rats. PMID- 24228063 TI - Antistress Effects of the Ethanolic Extract from Cymbopogon schoenanthus Growing Wild in Tunisia. AB - This study aimed to investigate the antistress properties of the ethanol extract of Cymbopogon schoenanthus (CSEE), growing wild in the southern part of Tunisia. The effect of extracts on H2O2-induced cytotoxicity and stress in human neuroblastoma SH-SY5Y cells. Its effect on stress-induced in ICR mice was exposed to force swim and tail suspension, in concordance with heat shock protein expression (HSP27 and HSP90), corticosterone, and catecholamine neurotransmitters level. Our results demonstrated that pretreatment of SH-SY5Y cells with CSEE at 1/2000, 1/1000, and 1/500 v/v dilutions significantly inversed H2O2-induced neurotoxicity. Moreover, CSEE treatments significantly reversed heat shock protein expression in heat-stressed HSP47-transformed cells (42 degrees C, for 90 min) and mRNA expression of HSP27 and HSP90 in H2O2-treated SH-SY5Y. Daily oral administration of 100 mg/kg and 200 mg/kg CSEE was conducted to ICR mice for 2 weeks. It was resulted in a significant decrease of immobility time in forced swimming and tail suspension tests. The effect of CSEE on animal behavior was concordant with a significant regulation of blood serum corticosterone and cerebral cortex levels of catecholamine (dopamine, adrenaline, and noradrenaline). Therefore, this study was attempted to demonstrate the preventive potential of CSEE against stress disorders at in vitro and in vivo levels. PMID- 24228064 TI - Efficacy of crest herbal toothpaste in "clearing internal heat": a randomized, double-blind clinical study. AB - Objective. Evaluation of the efficacy of Crest Herbal Crystal Toothpaste in "clearing internal heat." Methods. This was a randomized, double-blind, controlled parallel design clinical test of a product that was already on the market. 72 subjects were randomly assigned to control group (group A with Colgate Herbal Salty Toothpaste) or treatment group (group B with Crest Herbal Crystal Toothpaste) with ratio of 1 : 2. Subjects were instructed to brush with 1g toothpaste for 2 minutes each time, 2 times per day in a 4-aweek test period; measurement with the rating scale on the efficacy of "clearing internal heat" for the herbal toothpaste was done at baseline, 2 weeks, and 4 weeks of toothpaste usage. Results. The rating scale on efficacy of "clearing internal heat" for the herbal toothpaste reveals that the primitive points of 72-case intention-to-treat (ITT) analysis and 67-case per-protocol (PP) analysis for subjects in group A and subjects in group B were found to be reduced progressively with statistical significance (P < 0.05). The overall effective rates for group A and group B were, respectively, 62.50%, 56.25% (ITT) and 62.50%, 60.64% (PP). The statistical results indicated that the symptoms of fire-heat for both groups of subjects have been improved after application of toothpaste. Conclusion. The efficacy of Crest Herbal Crystal Toothpaste in "clearing internal heat" was confirmed by the trial as compared to Colgate Herbal Salty Toothpaste. And its efficacy was objectively evaluated by the rating scale on efficacy of "clearing internal heat." PMID- 24228065 TI - The physical effects of aromatherapy in alleviating work-related stress on elementary school teachers in taiwan. AB - People use aromatherapy to relieve the symptoms of physical and psychological stress. However, previous studies have not precisely clarified a scientific basis for the beneficial effects of aromatherapy. Therefore, the overall purpose of this study was to elucidate the beneficial effect of aromatherapy in relieving work-related stress. Twenty-nine elementary school teachers from Taiwan participated in this study. The experimental procedures comprised 2 phases. First, we verified the effect of aromatherapy by conducting 2 blind tests. We used natural bergamot essential oil extracted from plants and synthesized a chemical essential oil as the placebo to do the aromatherapy. Second, we analyzed the performance of the aromatherapy treatment on the teachers who had various workloads. We measured the teachers' heart rate variability to evaluate their autonomic nervous system activity. The results show that only the natural bergamot essential oil had an effect and that the aromatherapy treatment relieved work-related stress of teachers with various workloads. However, the aromatherapy treatment had a weak effect on young teachers who had a heavy workload. Moreover, the aromatherapy treatment exhibited no effect on teachers who belong to the abnormal body mass index subgroup having a heavy workload. PMID- 24228066 TI - Can cytomorphology of granulomas distinguish sarcoidosis from tuberculosis? Retrospective study of endobronchial ultrasound guided transbronchial needle aspirate of 49 granulomatous lymph nodes. AB - BACKGROUND: The differential diagnosis of tuberculosis (TB) and sarcoidosis on fine needle aspiration material is very challenging in tubercular endemic regions. We carried out a pilot study to explore cytomorphologic features of granulomas which could help in differentiation between sarcoidosis and TB. Final diagnoses in these patients were based on clinical, microbiologic and follow-up studies. MATERIALS AND METHODS: Endobronchial ultrasound guided transbronchial needle aspiration smears of 49 consecutive patients with a final cytologic diagnosis of granulomatous lymphadenitis were reviewed. Based on cytologic features two cytologic categories were enunciated and the results were correlated with microbiologic studies and/follow-up of minimum of 6 months. RESULTS: The cytologic categories did not correlate with the final clinical outcome of patients. CONCLUSIONS: Different patterns of granulomas observed in cytology smears do not help distinguish TB from sarcoidosis. The novel non-invasive techniques of mediastinal sampling though help in confirming granulomatous pathology, distinction between these entities and treatment decisions still depend upon correlating cytologic, microbiologic, clinical and radiological data in a large number of cases in tubercular endemic regions. PMID- 24228067 TI - Bone marrow elements in cerebrospinal fluid: Review of literature with a case study. AB - Presence of bone marrow elements in cerebrospinal fluid is rare. Journal publications on this topic are few and majority of them were written over a decade ago mostly as case reports in young children or the elderly. The increased cellularity and presence of myeloid precursors can be a pitfall and may be misdiagnosed as leukemia or lymphoma or central nervous system infection, when the specimen is actually not representative. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl. PMID- 24228070 TI - Efficacy and safety of laquinimod in multiple sclerosis: current status. AB - Laquinimod is a novel immunomodulatory agent, in development as a potential disease-modifying treatment for multiple sclerosis (MS). Structurally related to linomide, its pharmacological predecessor, laquinimod combines anti-inflammatory and possibly clinically relevant neuroprotective effects with the convenience of oral administration. In this review we aim to highlight the immunomodulatory and neuroprotective effects of laquinimod, and to describe its effects in animal models of MS. Furthermore, we focus on current results of clinical studies in MS. Randomized, controlled clinical trials in relapsing MS demonstrate a dose response effect on disease activity, measured by reduced clinical relapse rate, reduced number of brain MRI active lesions, as well as on sustained disability and brain atrophy. Laquinimod has a favourable tolerability and safety profile. A new phase III study, recently completed, will soon provide further details on the therapeutic potential of this drug. Laquinimod is a promising emerging treatment for relapsing-remitting MS that may provide a new therapeutic option in the near future. PMID- 24228069 TI - Protein expression profiles of intestinal epithelial co-cultures: effect of functionalised carbon nanotube exposure. AB - To assess the biological effects of low level, water dispersible, functionalised carbon nanotube (f-CNT) exposure in an in vitro model simulating the digestive tract, cellular protein expression was quantified and compared using label-free quantitative mass spectrometry (LFQMS). Co-cultured cells were exposed to well characterised SWCNT-COOH, MWCNT-COOH, and MWCNT-PVP. The relative expression of 2,282 unique proteins was compared across the dose groups. 428 proteins were found to be differentially expressed. At the high dose, the extent of differential protein expression was CNT-specific and directly related to CNT colloidal stability. Cells responded to low level MWCNT-PVP exposure with three fold greater differential expression. Bioinformatic analysis indicated significant and f-CNT-specific effects on relevant molecular and cellular functions and canonical pathways, with little overlap across f-CNT type and in the absence of overt toxicity. PMID- 24228068 TI - Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. AB - The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures. PMID- 24228072 TI - The role of neuroimaging in the diagnosis of headache disorders. AB - Headache is a common clinical feature in patients in the emergency room and in general neurology clinics. For physicians not experienced in headache disorders it might be difficult sometimes to decide in which patients neuroimaging is necessary to diagnose an underlying brain pathology and in which patients cerebral imaging is unnecessary. Most patients presenting to the primary-care physician with a nonacute headache and no further neurological signs or symptoms will not be suffering from an underlying serious condition. This review focuses on the main primary headache diseases, including migraine, tension-type headache and cluster headache, as well as frequent secondary headache entities with common clinical presentation and appropriate diagnostic and therapeutic algorithms to help guide the decision on the utilization of neuroimaging in the diagnostic workup. PMID- 24228071 TI - The cognitive side of essential tremor: what are the therapeutic implications? AB - While essential tremor (ET) has traditionally been categorized as a pure motor disease, cross-sectional and longitudinal studies of cognition in ET have demonstrated that these patients may have cognitive dysfunction. Recent epidemiological studies demonstrate an association between ET (particularly with onset after age 65) and increased risk for cognitive impairment and dementia. Although existing studies have generally conceptualized cognitive changes in ET as consistent with a 'frontosubcortical' or 'corticocerebellar' profile, results from these same studies suggest that cognitive impairment in ET may in fact be heterogeneous. Furthermore, the underlying mechanisms remain uncertain. Cognitive changes could be a byproduct of the cerebellar dysfunction of ET itself; alternately, they may be a feature of concomitant neurodegenerative diseases that have been associated in several studies with ET, including Alzheimer's disease, Parkinson's disease or progressive supranuclear palsy. While the study of cognitive dysfunction in ET has received research attention in recent years, the results of these studies have not been translated into the clinical domain and clinical practice. This review first summarizes the current literature on the potential relationships between ET and cognitive change. We then suggest areas of further clinical evaluation and treatment; these suggestions are directed at physicians caring for ET patients who may demonstrate or complain of cognitive impairment. As we discuss, clinicians should ideally screen ET patients for possible signs or symptoms of cognitive impairment in addition to assessing for psychiatric comorbidity and quality of life. These recommendations are in contrast to most current clinical practice, which does not routinely include such assessment among ET patients. To our knowledge, there have been no pharmacotherapeutic trials to date of any agent for cognitive change associated with ET. We believe that studies for this indication are now called for. Future efforts in this direction will also need to take into account the pathobiology of cognitive changes in ET, which itself is an area that is ripe for future investigations. PMID- 24228073 TI - Notch signalling in adult neurons: a potential target for microtubule stabilization. AB - Cytoskeletal dysfunction has been proposed during the last decade as one of the main mechanisms involved in the aetiology of several neurodegenerative diseases. Microtubules are basic elements of the cytoskeleton and the dysregulation of microtubule stability has been demonstrated to be causative for axonal transport impairment, synaptic contact degeneration, impaired neuronal function leading finally to neuronal loss. Several pathways are implicated in the microtubule assembly/disassembly process. Emerging evidence is focusing on Notch as a microtubule dynamics regulator. We demonstrated that activation of Notch signalling results in increased microtubule stability and changes in axonal morphology and branching. By contrast, Notch inhibition leads to an increase in cytoskeleton plasticity with intense neurite remodelling. Until now, several microtubule-binding compounds have been tested and the results have provided proof of concept that microtubule-binding agents or compounds with the ability to stabilize microtubules may have therapeutic potential for the treatment of Alzheimer's disease and other neurodegenerative diseases. In this review, based on its key role in cytoskeletal dynamics modulation, we propose Notch as a new potential target for microtubule stabilization. PMID- 24228074 TI - Kynurenines and other novel therapeutic strategies in the treatment of dementia. AB - Dementia is a common neuropsychological disorder with an increasing incidence. The most prevalent type of dementia is Alzheimer's disease. The underlying pathophysiological features of the cognitive decline are neurodegenerative processes, a cerebrovascular dysfunction and immunological alterations. The therapeutic approaches are still limited, although intensive research is being conducted with the aim of finding neuroprotective strategies. The widely accepted cholinesterase inhibitors and glutamate antagonists did not meet expectations of preventing disease progression, and research is therefore currently focusing on novel targets. Nonsteroidal anti-inflammatory drugs, secretase inhibitors and statins are promising drug candidates for the prevention and management of different forms of dementia. The kynurenine pathway has been associated with various neurodegenerative disorders and cerebrovascular diseases. This pathway is also closely related to neuroinflammatory processes and it has been implicated in the pathomechanisms of certain kinds of dementia. Targeting the kynurenine system may be of therapeutic value in the future. PMID- 24228075 TI - Health technologies for the improvement of chronic disease management: a review of the Medical Advisory Secretariat evidence-based analyses between 2006 and 2011. AB - BACKGROUND: As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). OBJECTIVE: The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. DATA SOURCES: The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. REVIEW METHODS: Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. RESULTS: Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. CONCLUSIONS: The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient outcomes; reduce resource utilization intensity; be cost-effective; and be a viable contributing factor to chronic disease management in the community. PLAIN LANGUAGE SUMMARY: People with chronic diseases rely on the health care system to help manage their illness. Hospital use can be costly, so community-based alternatives are often preferred. Research published in the Ontario Health Technology Assessment Series between 2006 and 2011 was reviewed to identify health technologies that have been effective or cost-effective in helping to manage chronic disease in the community. All technologies identified led to better patient outcomes and less use of health services. Most were also cost-effective. Two technologies that can cure chronic disease and 1 that can prevent chronic disease were found. Eight technologies that can help manage chronic disease were also found. Health technologies should be considered an important part of chronic disease management in the community. PMID- 24228076 TI - Optimizing chronic disease management mega-analysis: economic evaluation. AB - BACKGROUND: As Ontario's population ages, chronic diseases are becoming increasingly common. There is growing interest in services and care models designed to optimize the management of chronic disease. OBJECTIVE: To evaluate the cost-effectiveness and expected budget impact of interventions in chronic disease cohorts evaluated as part of the Optimizing Chronic Disease Management mega-analysis. DATA SOURCES: Sector-specific costs, disease incidence, and mortality were calculated for each condition using administrative databases from the Institute for Clinical Evaluative Sciences. Intervention outcomes were based on literature identified in the evidence-based analyses. Quality-of-life and disease prevalence data were obtained from the literature. METHODS: Analyses were restricted to interventions that showed significant benefit for resource use or mortality from the evidence-based analyses. An Ontario cohort of patients with each chronic disease was constructed and followed over 5 years (2006-2011). A phase-based approach was used to estimate costs across all sectors of the health care system. Utility values identified in the literature and effect estimates for resource use and mortality obtained from the evidence-based analyses were applied to calculate incremental costs and quality-adjusted life-years (QALYs). Given uncertainty about how many patients would benefit from each intervention, a system-wide budget impact was not determined. Instead, the difference in lifetime cost between an individual-administered intervention and no intervention was presented. RESULTS: Of 70 potential cost-effectiveness analyses, 8 met our inclusion criteria. All were found to result in QALY gains and cost savings compared with usual care. The models were robust to the majority of sensitivity analyses undertaken, but due to structural limitations and time constraints, few sensitivity analyses were conducted. Incremental cost savings per patient who received intervention ranged between $15 per diabetic patient with specialized nursing to $10,665 per patient wth congestive heart failure receiving in-home care. LIMITATIONS: Evidence used to inform estimates of effect was often limited to a single trial with limited generalizability across populations, interventions, and health care systems. Because of the low clinical fidelity of health administrative data sets, intermediate clinical outcomes could not be included. Cohort costs included an average of all health care costs and were not restricted to costs associated with the disease. Intervention costs were based on resource use specified in clinical trials. CONCLUSIONS: Applying estimates of effect from the evidence-based analyses to real-world resource use resulted in cost savings for all interventions. On the basis of quality-of-life data identified in the literature, all interventions were found to result in a greater QALY gain than usual care would. Implementation of all interventions could offer significant cost reductions. However, this analysis was subject to important limitations. PLAIN LANGUAGE SUMMARY: Chronic diseases are the leading cause of death and disability in Ontario. They account for a third of direct health care costs across the province. This study aims to evaluate the cost-effectiveness of health care interventions that might improve the management of chronic diseases. The evaluated interventions led to lower costs and better quality of life than usual care. Offering these options could reduce costs per patient. However, the studies used in this analysis were of medium to very low quality, and the methods had many limitations. PMID- 24228078 TI - Chronic disease patients' experiences with accessing health care in rural and remote areas: a systematic review and qualitative meta-synthesis. AB - BACKGROUND: Rurality can contribute to the vulnerability of people with chronic diseases. Qualitative research can identify a wide range of health care access issues faced by patients living in a remote or rural setting. OBJECTIVE: To systematically review and synthesize qualitative research on the advantages and disadvantages rural patients with chronic diseases face when accessing both rural and distant care. DATA SOURCES: This report synthesizes 12 primary qualitative studies on the topic of access to health care for rural patients with chronic disease. Included studies were published between 2002 and 2012 and followed adult patients in North America, Europe, Australia, and New Zealand. REVIEW METHODS: Qualitative meta-synthesis was used to integrate findings across primary research studies. RESULTS: Three major themes were identified: geography, availability of health care professionals, and rural culture. First, geographic distance from services poses access barriers, worsened by transportation problems or weather conditions. Community supports and rurally located services can help overcome these challenges. Second, the limited availability of health care professionals (coupled with low education or lack of peer support) increases the feeling of vulnerability. When care is available locally, patients appreciate long-term relationships with individual clinicians and care personalized by familiarity with the patient as a person. Finally, patients may feel culturally marginalized in the urban health care context, especially if health literacy is low. A culture of self-reliance and community belonging in rural areas may incline patients to do without distant care and may mitigate feelings of vulnerability. LIMITATIONS: Qualitative research findings are not intended to generalize directly to populations, although meta-synthesis across a number of qualitative studies builds an increasingly robust understanding that is more likely to be transferable. Selected studies focused on the vulnerability experiences of rural dwellers with chronic disease; findings emphasize the patient rather than the provider perspective. CONCLUSIONS: This study corroborates previous knowledge and concerns about access issues in rural and remote areas, such as geographical distance and shortage of health care professionals and services. Unhealthy behaviours and reduced willingness to seek care increase patients' vulnerability. Patients' perspectives also highlight rural culture's potential to either exacerbate or mitigate access issues. PLAIN LANGUAGE SUMMARY: People who live in a rural area may feel more vulnerable--that is, more easily harmed by their health problems or experiences with the health care system. Qualitative research looks at these experiences from the patient's point of view. We found 3 broad concerns in the studies we looked at. The first was geography: needing to travel long distances for health care can make care hard to reach, especially if transportation is difficult or the weather is bad. The second concern was availability of health professionals: rural areas often lack health care services. Patients may also feel powerless in "referral games" between rural and urban providers. People with low education or without others to help them may find navigating care more difficult. When rural services are available, patients like seeing clinicians who have known them for a long time, and like how familiar clinicians treat them as a whole person. The third concern was rural culture: patients may feel like outsiders in city hospitals or clinics. As well, in rural communities, people may share a feeling of self-reliance and community belonging. This may make them more eager to take care of themselves and each other, and less willing to seek distant care. Each of these factors can increase or decrease patient vulnerability, depending on how health services are provided. PMID- 24228077 TI - How diet modification challenges are magnified in vulnerable or marginalized people with diabetes and heart disease: a systematic review and qualitative meta synthesis. AB - BACKGROUND: Diet modification is an important part of self-management for patients with diabetes and/or heart disease (including coronary artery disease, heart failure, and atrial fibrillation). Many health care providers and community based programs advise lifestyle and diet modification as part of care for people with these conditions. This report synthesizes qualitative information on how patients respond differently to the challenges of diet modification. Qualitative and descriptive evidence can illuminate challenges that may affect the success and equitable impact of dietary modification interventions. OBJECTIVES: To (a) examine the diet modification challenges faced by diabetes and/or heart disease patients; and (b) compare and contrast the challenges faced by patients who are members of vulnerable and nonvulnerable groups as they change their diet in response to clinical recommendations. DATA SOURCES: This report synthesizes 65 primary qualitative studies on the topic of dietary modification challenges encountered by patients with diabetes and/or heart disease. Included papers were published between 2002 and 2012 and studied adult patients in North America, Europe, and Australia/New Zealand. REVIEW METHODS: Qualitative meta-synthesis was used to integrate findings across primary research studies. RESULTS: Analysis identified 5 types of challenges that are common to both vulnerable and nonvulnerable patients: self-discipline, knowledge, coping with everyday stress, negotiating with family members, and managing the social significance of food. Vulnerable patients may experience additional barriers, many of which can magnify or exacerbate those common challenges. LIMITATIONS: While qualitative insights are robust and often enlightening for understanding experiences and planning services in other settings, they are not intended to be generalizable. The findings of the studies reviewed here--and of this synthesis--do not strictly generalize to the Ontario (or any specific) population. This evidence must be interpreted and applied carefully, in light of expertise and the experiences of the relevant community. CONCLUSIONS: Diet modification is not simply a matter of knowing what to eat and making the rational choice to change dietary practices. Rather, diet and eating practices should be considered as part of the situated lives of patients, requiring an individualized approach that is responsive to the conditions in which each patient is attempting to make a change. Common challenges include self-discipline, knowledge, coping with everyday stress, negotiating with family members, and managing the social significance of food. An individualized approach is particularly important when working with patients who have vulnerabilities. PLAIN LANGUAGE SUMMARY: Health care providers often encourage people with diabetes and/or heart disease to change their diet. They advise people with diabetes to eat less sugar, starch, and fat. They advise people with heart disease to eat less fat and salt. However, many patients find it difficult to change what they eat. This report examines the challenges people may face when making such changes. It also examines the special challenges faced by people who are vulnerable due to other factors, such as poverty, lack of education, and difficulty speaking English. Five themes were common to all people who make diet changes: self-discipline, knowledge, coping with stress, negotiating with family members, and managing the social aspect of food. Members of vulnerable groups also reported other challenges, such as affording fresh fruit and vegetables or understanding English instructions. This report may help health care providers work with patients more effectively to make diet changes. PMID- 24228079 TI - Patient experiences of depression and anxiety with chronic disease: a systematic review and qualitative meta-synthesis. AB - BACKGROUND: Depression and anxiety are highly prevalent in patients with chronic disease, but remain undertreated despite significant negative consequences on patient health. A number of clinical groups have developed recommendations for depression screening practices in the chronic disease population. OBJECTIVES: The objective of this analysis was to review empirical qualitative research on the experiences of patients with chronic disease (e.g., COPD, diabetes, heart disease, stroke) and comorbid depression or anxiety, and to highlight the implications of the screening and management of anxiety and/or depression on chronic disease outcomes. REVIEW METHODS: We performed literature searches for studies published from January 2002 to May 2012. We applied a qualitative mega filter to nine condition-specific search filters. Titles and abstracts were reviewed by two reviewers and, for the studies that met the eligibility criteria, full-text articles were obtained. Qualitative meta-synthesis was used to integrate findings across relevant published primary research studies. Qualitative meta-synthesis produced a synthesis of evidence that both retained the original meaning of the authors and offered a new, integrative interpretation of the phenomenon through a process of comparing and contrasting findings across studies. RESULTS: The findings of 20 primary qualitative studies were synthesized. Patients tended to experience their chronic conditions and anxiety or depression as either independent or inter-related (i.e., the chronic disease lead to depression/anxiety, the depression/anxiety lead to the chronic disease, or the two conditions exacerbated each other). Potential barriers to screening for depression or anxiety were also identified. LIMITATIONS: A wider array of issues might have been captured if the analysis had focused on broader psychological responses to the chronic disease experience. However, given the objective to highlight implications for screening for anxiety or depression, the more narrow focus seemed most relevant. CONCLUSIONS: Chronic disease and anxiety or depression can be independent or inter-related. Patients may be reluctant to acknowledge depression or anxiety as a separate condition, or may not recognize that the conditions are separate because of overlapping physical symptoms. More qualitative research is needed to specifically address screening for depression or anxiety. PLAIN LANGUAGE SUMMARY: Depression is a common complication of chronic disease. It may worsen the disease, and it may also affect the self management of the disease. Screening for depression earlier, and then treating it, may reduce distress and improve symptoms of the chronic disease, leading to better quality of life. PMID- 24228080 TI - Experiences of patient-centredness with specialized community-based care: a systematic review and qualitative meta-synthesis. AB - BACKGROUND: Specialized community-based care (SCBC) endeavours to help patients manage chronic diseases by formalizing the link between primary care providers and other community providers with specialized training. Many types of health care providers and community-based programs are employed in SCBC. Patient-centred care focuses on patients' psychosocial experience of health and illness to ensure that patients' care plans are modelled on their individual values, preferences, spirituality, and expressed needs. OBJECTIVES: To synthesize qualitative research on patient and provider experiences of SCBC interventions and health care delivery models, using the core principles of patient-centredness. DATA SOURCES: This report synthesizes 29 primary qualitative studies on the topic of SCBC interventions for patients with chronic conditions. Included studies were published between 2002 and 2012, and followed adult patients in North America, Europe, Australia, and New Zealand. REVIEW METHODS: Qualitative meta-synthesis was used to integrate findings across primary research studies. RESULTS: Three core themes emerged from the analysis: patients' health beliefs affect their participation in SCBC interventions;patients' experiences with community-based care differ from their experiences with hospital-based care;patients and providers value the role of nurses differently in community-based chronic disease care. LIMITATIONS: Qualitative research findings are not intended to generalize directly to populations, although meta-synthesis across several qualitative studies builds an increasingly robust understanding that is more likely to be transferable. The diversity of interventions that fall under SCBC and the cross interventional focus of many of the studies mean that findings might not be generalizable to all forms of SCBC or its specific components. CONCLUSIONS: Patients with chronic diseases who participated in SCBC interventions reported greater satisfaction when SCBC helped them better understand their diagnosis, facilitated increased socialization, provided them with a role in managing their own care, and assisted them in overcoming psychological and social barriers. PLAIN LANGUAGE SUMMARY: More and more, to reduce bed shortages in hospitals, health care systems are providing programs called specialized community-based care (SCBC) to patients with chronic diseases. These SCBC programs allow patients with chronic diseases to be managed in the community by linking their family physicians with other community-based health care providers who have specialized training. This report looks at the experiences of patients and health care providers who take part in SCBC programs, focusing on psychological and social factors. This kind of lens is called patient-centred. Three themes came up in our analysis: patients' health beliefs affect how they take part in SCBC interventions; patients' experiences with care in the community differ from their experiences with care in the hospital; patients and providers value the role of nurses differently. The results of this analysis could help those who provide SCBC programs to better meet patients' needs. PMID- 24228081 TI - Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis. AB - OBJECTIVE: The objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children. DATA SOURCES: A literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012. REVIEW METHODS: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed. RESULTS: The search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children. LIMITATIONS: We found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance. CONCLUSIONS: Based on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as effective at reducing seizure frequency, but children had significantly fewer hospitalizations and ED visits after VNS implantation. Despite the considerable risks associated with these invasive procedures, long term adverse events appear to be limited. PLAIN LANGUAGE SUMMARY: Electrical stimulation of specific areas of the brain is a procedure used to control epileptic seizures when more conventional treatments are not working. Most adults and children with epilepsy are able to control their seizures with medication, but for some patients, drugs are not effective and surgery to remove the part of the brain where the seizures start is not an appropriate option. This study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; we found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures. PMID- 24228082 TI - Carbon-13 urea breath test for Helicobacter pylori infection in patients with uninvestigated ulcer-like dyspepsia: an evidence-based analysis. AB - BACKGROUND: Dyspepsia is a condition defined by chronic pain or discomfort in the upper gastrointestinal tract that can be caused by Helicobacter pylori. The carbon-13 urea breath test (13C UBT) is a non-invasive test to detect H. pylori. OBJECTIVES: We aimed to determine the diagnostic accuracy and clinical utility of the 13C UBT in adult patients with ulcer-like dyspepsia who have no alarm features. DATA SOURCES: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2003 and 2012. REVIEW METHODS: We abstracted the sensitivity and specificity, which were calculated against a composite reference standard. Summary estimates were obtained using bivariate random effects regression analysis. RESULTS: From 19 diagnostic studies, the 13C UBT summary estimates were 98.1% (95% confidence interval [CI], 96.3-99.0) for sensitivity and 95.1% (95% CI, 90.3-97.6) for specificity. In 6 studies that compared the 13C UBT with serology, the 113C UBT sensitivity was 95.0% (95% CI, 90.1-97.5) and specificity was 91.6 % (95% CI, 81.3-96.4). The sensitivity and specificity for serology were 92.9% (95% CI, 82.6-97.3) and 71.1% (95% CI, 63.8-77.5), respectively. In 1 RCT, symptom resolution, medication use, and physician visits were similar among the 13C UBT, serology, gastroscopy, or empirical treatment arms. However, patients tested with 13C UBT reported higher dyspepsia-specific quality of life scores. LIMITATIONS: Processing of the 13C UBT results can vary according to many factors. Further, the studies showed significant heterogeneity and used different composite reference standards. CONCLUSIONS: The 13C UBT is an accurate test with high sensitivity and specificity. Compared with serology, it has higher specificity. There is a paucity of data on the 13C UBT beyond test accuracy. PLAIN LANGUAGE SUMMARY: Breath test for detecting bacteria in patients with ulcer-like symptoms. Dyspepsia is a condition that causes long-term pain or discomfort in the upper abdomen. Symptoms can include heartburn, burping, bloating, nausea, or slow digestion. Dyspepsia can be caused by a bacterium that also causes ulcers and stomach cancer. Half of the world's people are believed to be infected with these bacteria. A test has been developed to detect the bacteria in a breath sample. Our review determined the accuracy of this breath test in adults with ulcer-like symptoms. From 19 studies, the breath test correctly identified 98% of patients with the bacteria and 95% of patients without the bacteria, as determined by a reference standard. Six studies compared the breath test to a blood test that is currently used. Both the breath and blood tests performed well in correctly identifying patients with the bacteria. However, the blood test was incorrectly positive in 20 more patients who did not have the bacteria according to the breath test. This means that more patients would have received unnecessary treatment. Thus, the breath test is an accurate test to detect the bacteria in adult patients who have ulcer-like symptoms. But the many differences among the studies in our review included several steps taken to perform the breath test and the reference standards used to compare a blood test with the breath test. PMID- 24228083 TI - Cost-effectiveness of the carbon-13 urea breath test for the detection of Helicobacter pylori: an economic analysis. AB - OBJECTIVES: This analysis aimed to evaluate the cost-effectiveness of various testing strategies for Helicobacter pylori in patients with uninvestigated dyspepsia and to calculate the budgetary impact of these tests for the province of Ontario. DATA SOURCES: Data on the sensitivity and specificity were obtained from the clinical evidence-based analysis. Resource items were obtained from expert opinion, and costs were applied on the basis of published sources as well as expert opinion. REVIEW METHODS: A decision analytic model was constructed to compare the costs and outcomes (false-positive results, false-negative results, and misdiagnoses avoided) of the carbon-13 (13C) urea breath test (UBT), enzyme linked immunosorbent assay (ELISA) serology test, and a 2-step strategy of an ELISA serology test and a confirmatory 13C UBT based on the sensitivity and specificity of the tests and prevalence estimates. RESULTS: The 2-step strategy is more costly and more effective than the ELISA serology test and results in $210 per misdiagnosis case avoided. The 13C UBT is dominated by the 2-step strategy, i.e., it is more costly and less effective. The budget impact analysis indicates that it will cost $7.9 million more to test a volume of 129,307 patients with the 13C UBT than with ELISA serology, and $4.7 million more to test these patients with the 2-step strategy. LIMITATIONS: The clinical studies that were pooled varied in the technique used to perform the breath test and in reference standards used to make comparisons with the breath test. However, these parameters were varied in a sensitivity analysis. The economic model was designed to consider intermediate outcomes only (i.e., misdiagnosed cases) and was not a complete model with final patient outcomes (e.g., quality-adjusted life years). CONCLUSIONS: Results indicate that the 2-step strategy could be economically attractive for the testing of H. pylori. However, testing with the 2-step strategy will cost the Ministry of Health and Long-Term Care $4.7 million more than with the ELISA serology test. PMID- 24228084 TI - Hysteroscopic tubal sterilization: an evidence-based analysis. AB - BACKGROUND: Hysteroscopic tubal sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. The procedures involves non-surgical placement of permanent microinserts into both fallopian tubes. Patients must use alternative contraception for at least 3 months postprocedure until tubal occlusion is confirmed. Compared to tubal ligation, potential advantages of the hysteroscopic procedure are that it can be performed in 10 minutes in an office setting without the use of general or even local anesthesia. OBJECTIVE: The objective of this analysis was to determine the effectiveness and safety of hysteroscopic tubal sterilization compared with tubal ligation for permanent female sterilization. DATA SOURCES: A standard systematic literature search was conducted for studies published from January 1, 2008, until December 11, 2012. REVIEW METHODS: Observational studies, randomized controlled trials (RCTs), systematic reviews and meta-analyses with 1 month or more of follow-up were examined. Outcomes included failure/pregnancy rates, adverse events, and patient satisfaction. RESULTS: No RCTs were identified. Two systematic reviews covered 22 observational studies of hysteroscopic sterilization. Only 1 (N = 93) of these 22 studies compared hysteroscopic sterilization to laparoscopic tubal ligation. Two other noncomparative case series not included in the systematic reviews were also identified. In the absence of comparative studies, data on tubal ligation were derived for this analysis from the CREST study, a large, multicentre, prospective, noncomparative observational study in the United States (GRADE low). Overall, hysteroscopic sterilization is associated with lower pregnancy rates and lower complication rates compared to tubal ligation. No deaths have been reported for hysteroscopic sterilization. LIMITATIONS: A lack of long-term follow-up for hysteroscopic sterilization and a paucity of studies that directly compare the two procedures limit this assessment. In addition, optimal placement of the microinsert at the time of hysteroscopy varied among studies. CONCLUSIONS: Hysteroscopic sterilization is associated with: lower pregnancy rates compared to tubal ligation (GRADE very low); lower complication rates compared to tubal ligation (GRADE very low); no significant improvement in patient satisfaction compared to tubal ligation (GRADE very low). PLAIN LANGUAGE SUMMARY: Hysteroscopic tubal sterilization is a minimally invasive alternative to conventional tubal ligation for women who want a permanent method of contraception. Both approaches involve closing off the fallopian tubes, preventing the egg from moving down the tube and the sperm from reaching the egg. Tubal ligation is a surgical procedure to tie or seal the fallopian tubes, and it usually requires general anesthesia. In contrast, hysteroscopic tubal sterilization can be performed in 10 minutes in an office setting without general or even local anesthesia. A tiny device called a microinsert is inserted into each fallopian tube through the vagina, cervix, and uterus without surgery. An instrument called a hysteroscope allows the doctor to see inside the body for the procedure. Once the microinserts are in place, scar tissue forms around them and blocks the fallopian tubes. Health Quality Ontario conducted a review of the effectiveness and safety of hysteroscopic tubal sterilization compared to tubal ligation. This review indicates that hysteroscopic tubal sterilization is associated with: lower pregnancy rates compared to tubal ligation; lower complication rates compared to tubal ligation; no significant improvement in patient satisfaction compared to tubal ligation. However, we found a number of limitations to the studies available on hysteroscopic tubal sterilization. Among other concerns, most studies did not include long-term follow-up and only 1 study directly compared hysteroscopic tubal sterilization to tubal ligation. PMID- 24228085 TI - Hysteroscopic tubal sterilization: a health economic literature review. AB - BACKGROUND: Hysteroscopic sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. In contrast to the laparoscopic technique, a hysteroscope is used to pass permanent microinserts through the cervix and place them in the fallopian tubes. This procedure does not require local or general anesthesia and can be performed in an office setting. OBJECTIVES: The objective of this analysis was to determine, based on published literature, the cost-effectiveness of hysteroscopic tubal sterilization (HS) compared with laparoscopic tubal ligation (LS) for permanent female sterilization. DATA SOURCES: A systematic literature search was conducted for studies published between January 1, 2008, and December 11, 2012. REVIEW METHODS: Potentially relevant studies were identified based on the title and abstract. Cost-utility analyses (studies that report outcomes in terms of costs and quality-adjusted life-years) were prioritized for inclusion. When not available, cost-effectiveness, cost-benefit, and cost-consequence analyses were considered. Costing studies were considered in the absence of all other analyses. RESULTS: A total of 33 abstracts were identified. Three cost analyses were included. A retrospective chart review from Canada found that HS was $111 less costly than LS; a prospective activity-based cost management study from Italy reported that it was ?337 less costly than LS; and the results of an American decision model showed that HS was $1,178 less costly than LS. LIMITATIONS: All studies had limited applicability to the Ontario health care system due to differences in setting, resource use, and costs. CONCLUSIONS: Three cost analyses found that, although the HS procedure was more expensive due to the cost of the microinserts, HS was less costly than LS overall due to the shorter recovery time required. PLAIN LANGUAGE SUMMARY: Hysteroscopic sterilization is a minimally invasive alternative to conventional tubal ligation for women who want a permanent method of contraception. Both approaches involve closing off the fallopian tubes, preventing the egg from moving down the tube and the sperm from reaching the egg. Tubal ligation is a surgical procedure to tie or seal the fallopian tubes, and it usually requires general anesthesia. In contrast, hysteroscopic tubal sterilization can be performed in 10 minutes in an office setting without general or even local anesthesia. A tiny device called a microinsert is inserted into each fallopian tube through the vagina, cervix, and uterus without surgery. An instrument called a hysteroscope allows the doctor to see inside the body for the procedure. Once the microinserts are in place, scar tissue forms around them and blocks the fallopian tubes. Health Quality Ontario commissioned a systematic review of published economic literature to determine whether hysteroscopic sterilization is cost-effective compared to tubal ligation. This review did not find any studies that reported results in terms of both costs and effectiveness or costs and quality-adjusted life-years. We did find 3 costing studies and included them in our review. All of these studies found that when hysteroscopic sterilization was performed as an outpatient procedure, it was less expensive than tubal ligation due to a shorter recovery time. However, none of the studies apply directly to Ontario because of differences in our health care system compared to those in the studies. PMID- 24228086 TI - Association between sleep duration and 24-hour urine free cortisol in the MrOS Sleep Study. AB - CONTEXT: Short sleep duration is associated with adverse health outcomes, but the mechanisms involved are unknown. It has been postulated that short sleep duration may elevate cortisol levels, but studies have had conflicting results. It is unclear whether these differing findings may be due to methodological issues, such as assessment of sleep duration. Specifically, objective versus subjective methods of measuring habitual sleep duration may account for the conflicting results found in epidemiological studies. OBJECTIVE: Our goal was to determine whether habitual sleep duration, measured objectively (by actigraphy) and subjectively (by self-report), was associated with 24-hour urine free cortisol (UFC), a measure of integrated cortisol secretion. Our secondary goal was to determine whether slow wave sleep (SWS, determined by polysomnography) was associated with 24-hour UFC. DESIGN/SETTING: Cross sectional study of community dwelling older men. PATIENTS/PARTICIPANTS: 325 men (mean age = 76.6 years, SD = 5.5) from the Portland site of the MrOS Sleep Study, who underwent 24-hour urine collection, polysomnography, actigraphy and sleep questionnaire. PRIMARY OUTCOME: 24-hour UFC. RESULTS: In this study of community dwelling older men, self reported sleep duration was inversely related to 24-hour UFC levels. Participants reporting <5 hours of habitual sleep had an adjusted mean 24-hour UFC of 29.8 ug, compared to 28.0 ug in participants reporting >5 to <8 hours of sleep 25.5 ug in those reporting >8 hours of habitual sleep. However, sleep duration determined by actigraphy was not associated with 24-hour UFC in either univariable or multivariable regression models. SWS was not associated with 24-hour UFC. CONCLUSION: Objectively measured (i.e., actigraphic) sleep duration is not associated with 24-hour UFC in these community dwelling older men. This finding, together with prior studies, suggests that elevated levels of integrated cortisol secretion is not the mechanisms by which short sleep duration leads to adverse health outcomes. PMID- 24228087 TI - ULtiMATE system for rapid assembly of customized TAL effectors. AB - Engineered TAL-effector nucleases (TALENs) and TALE-based constructs have become powerful tools for eukaryotic genome editing. Although many methods have been reported, it remains a challenge for the assembly of designer-based TALE repeats in a fast, precise and cost-effective manner. We present an ULtiMATE (USER-based Ligation Mediated Assembly of TAL Effector) system for speedy and accurate assembly of customized TALE constructs. This method takes advantage of uracil specific excision reagent (USER) to create multiple distinct sticky ends between any neighboring DNA fragments for specific ligation. With pre-assembled templates, multiple TALE DNA-binding domains could be efficiently assembled in order within hours with minimal manual operation. This system has been demonstrated to produce both functional TALENs for effective gene knockout and TALE-mediated gene-specific transcription activation (TALE-TA). The feature of both ease-of-operation and high efficiency of ULtiMATE system makes it not only an ideal method for biologic labs, but also an approach well suited for large scale assembly of TALENs and any other TALE-based constructions. PMID- 24228088 TI - The SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma: relationship with extracellular matrix remodeling. AB - Synovial sarcoma (SS) tumor cells, which have the chromosomal translocation t(X;18)(p11.2;q11.2), have an inherently greater propensity for epithelial differentiation than other mesenchymal tumors, especially spindle cell sarcomas. This is caused by de-repression of the transcription of E-cadherin by SYT-SSX1 and SYT-SSX2, which dissociate Snail or Slug, respectively, from the E-cadherin promoter. However, a subset of SS with SYT-SSX1 loses E-cadherin expression despite adequate de-repression because of mutations in E-cadherin, resulting in monophasic histology. The ratio of the expression levels of SYT-SSX1 and Snail is also associated with E-cadherin expression: the lower the SYT-SSX1/Snail ratio, the lower the level of E-cadherin expression, and vice versa, thus affecting tumor histology. In addition, Wnt signal activation caused by mutation of beta catenin, APC, or Axin 1 and 2 is associated with monophasic histology. Remodeling of the extracellular matrix is also important. Only cells that survive all of these steps can finally exhibit biphasic histology. On the other hand, the SYT SSX2 fusion has a weaker de-repression effect on the E-cadherin promoter than does SYT-SSX1, so it is difficult for SYT-SSX2-expressing tumors to achieve sufficient capacity for epithelial differentiation to form glandular structures. This review provides an interesting model for this epithelial differentiation that shows a possible mechanism for the aberrant mesenchymal to epithelial transition of SS and suggests that it might better be considered an epithelial to mesenchymal transition. PMID- 24228090 TI - New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model. AB - The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey's test, considering statistical significance when p<0.1. Adequate bone repair was observed in the membrane-covered defects. At 3 weeks, organization of the tissue, bone formation from the periphery of the defect and the absence of inflammatory infiltrate were observed in both experimental groups, but the defect covered with absorbable membrane presented statistically greater bone formation. At 8 weeks, both membrane-covered defects showed adequate bone formation without significant differences, although they did in fact present differences with the control defect in both periods (p>0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects. PMID- 24228089 TI - The effect of porcine ADM to improve the burn wound healing. AB - To study the effect of porcine acellular dermal matrix (ADM) on the burn wound healing. Seventy healthy Wistar rats were inflicted with 2 cm second degree burn and divided into 2 groups; one group was treated with porcine ADM and the other with Povidone Iodine Cream. Biopsies were taken on day 1, 3, 5, 7, 10, 14, 21 for histopathological and biochemical analysis to test PCNA, K19, Integrin-beta1, PDGF, EGF and FGF. The results revealed relatively better and faster regeneration after treatment of porcine ADM, along with greatly increased synthesis in collagen in the experimental group. PCNA, K19, Integrin-beta1 had an increase and then tapered down, and were stronger in the experimental group than in the contrast group during 21 days after burns. PDGF, EGF and FGF levels increased on day 3, peaked on day 5 and then started to decrease, while significantly enhanced expression of relevant growth factors were observed in the experimental group. Porcine ADM stimulate collagen synthesis, stem cells proliferation and differentiation, and the expression of relevant growth factors and ultimately improve the burn wound healing. PMID- 24228091 TI - Expression and clinical significance of the nin one binding protein and p38 MAPK in prostate carcinoma. AB - BACKGROUND: Prostate carcinoma is a major cause of morbidity and mortality. The MAPK Signaling Pathway plays an important role in multiple tumors, including prostate carcinoma. MAPK signaling is mediated by ERK1/2, JNK and p38 MAPK, which are important in the control of cell proliferation, differentiation and apoptosis. However, relatively little is known about the regulatory mechanism of p38 MAPK in prostate cancers. NOB1 is among the most novel topic in MAPK studies currently. Recent studies found its vital role in tumor metastasis in glioblastoma proliferation, however, its expression profile and its prognostic value in prostate carcinoma have not been investigated. METHODS: To determine the relationship between NOB1 and p38 MAPK expressions, a population-based study was conducted for immunohistochemical staining analysis of tumor tissues, in matched malignant and nonmalignant prostatectomy samples from 132 PCa patients. Moreover, Western blot analysis and NOB1 interference studies of prostate cancer cell lines. To evaluate the diagnostic and prognostic between NOB1 and p38 MAPK in prostate cancer (PCa) tissue after radical prostatectomy, the hypothesis that prostate cancers with NOB1 expression have distinct clinical, prognostic and molecular attributes was tested. RESULTS: Among 132 prostate cancers, NOB1 expression was detected in 117 (88.7%) tumors by immunohistochemistry. NOB1 and p38 MAPK expression had significant positive correlation with carcinogenesis, tumor progression and patient survival. Immunohistochemically, NOB1 expression in prostate cancer was independently associated with p38 MAPK activation (P=0.0002). Furthermore, p38 MAPK expression was completely suppressed by NOB1 interference in the prostate cancer cell lines DU-145 and PC-3. CONCLUSIONS: NOB1 expression status was closely correlated with important histopathologic characteristics and the recurrence and metastasis of prostate carcinomas. These data support a potential link between NOB1 and p38 MAPK, and suggest that NOB1 may identify a subset of prostate cancer patients with a poor prognosis. This study proved that NOB1 in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools. PMID- 24228092 TI - Influences of HIF-lalpha on Bax/Bcl-2 and VEGF expressions in rats with spinal cord injury. AB - Hypoxia-inducible factor 1-alpha (HIF-1alpha) is a subunit of HIF-l and thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. This study aimed to investigated whether recombinant adenovirus vector over-expressing HIF-lalpha could affect apoptosis-related proteins (Bcl-2 and Bax) and vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model. A total of 60 male SD rats were divided into 4 groups: Sham, Control, Ad-Blank and Ad-HIF-1alpha groups. 1, 3, 7, 14, 28 days after surgery, the behavioral recovery was evaluated with BBB scales. Then, rats were sacrificed and the spinal cord was collected for detection of Bcl-2, Bax and VEGF expressions by immunohistochemistry. Results showed the Bcl-2, Bax, VEGF and HIF-lalpha expressions increased in animals with SCI, but the increase in Bcl-2, VEGF and HIF-lalpha expressions were higher in Ad-HIF-1alpha group when compared with other groups, but Bax expression decreased significantly. In addition, administration of Ad-HIF-1alpha significantly reduced apoptotic cells and promoted the recovery of neurological function. In conclusion, administration of Ad-HIF-1alpha after SCI could ameliorate neuronal apoptosis and promote angiogenesis in rats. Our study provides a basis for further exploration of the relationship between HIF1alpha and SCI. PMID- 24228093 TI - Suppressing the malignant phenotypes of glioma cells by lentiviral delivery of small hairpin RNA targeting hypoxia-inducible factor-1alpha. AB - Hypoxic microenvironment of solid tumors is known to shape malignant phenotypes of cancer cells through the dimeric transcription factor hypoxia-inducible factor (HIF)-1. In the present study, the therapeutic effect of targeting alpha subunit of HIF-1 in glioma cells via lentiviral delivery of small hairpin RNA (shRNA) was evaluated. Data from quantitative real-time PCR and immunohistochemistry demonstrated that HIF-1alpha was progressively upregulated during the development of gliomas. Lentiviral shRNA targeting HIF-1alpha led to substantial loss of cell viability, G0/G1-phase cell cycle arrest, apoptosis, and impairment of cell motility and invasiveness in human glioma U87MG cells. Xenograft experiments in nude mice further showed that HIF-1alpha-shRNA inhibited tumor growth and caused persistent repression of HIF-1alpha and its target genes, including VEGF, GLUT1 and MMP2, up to 25 days post-inoculation. Taken together, lentiviral delivery of shRNA is a promising therapeutic approach for targeting HIF-1alpha in glioma. PMID- 24228094 TI - Effects of low-frequency noise on cardiac collagen and cardiomyocyte ultrastructure: an immunohistochemical and electron microscopy study. AB - INTRODUCTION: Low-frequency noise (LFN) leads to the development of tissue fibrosis. We previously reported the development of myocardial and perivascular fibrosis and a reduction of cardiac connexin43 in rats, but data is lacking concerning the affected type of collagen as well as the ultrastructural myocardial modifications. OBJECTIVES: The aim of this study was to quantify cardiac collagens I and III and to evaluate myocardial ultrastructural changes in Wistar rats exposed to LFN. METHODS: Two groups of rats were considered: A LFN exposed group with 8 rats continuously submitted to LFN during 3 months and a control group with 8 rats. The hearts were sectioned and the mid-ventricular fragment was selected. After immunohistochemical evaluation, quantification of the collagens and muscle were performed using the image J software in the left ventricle, interventricular septum and right ventricle and the collagen I/muscle and collagen III/muscle ratios were calculated. Transmission electron microscopy (TEM) was used to analyze mid-ventricular samples taken from each group. RESULTS: The collagen I/muscle and collagen III/muscle ratios increased in totum respectively 80% (p<0.001) and 57.4% (p<0.05) in LFN-exposed rats. TEM showed interstitial collagen deposits and changes in mitochondria and intercalated discs of the cardiomyocytes in LFN-exposed animals. CONCLUSIONS: LFN increases collagen I and III in the extracellular matrix and induces ultrastructural alterations in the cardiomyocytes. These new morphological data open new and promising paths for further experimental and clinical research regarding the cardiac effects of low frequency noise. PMID- 24228095 TI - Protective effect of curcumin on chemotherapy-induced intestinal dysfunction. AB - OBJECTIVE: Chemotherapy is one of most important treatments for human cancers. However, side effects such as intestine dysfunction significantly impaired its clinical efficacy. This study aimed to investigate the protective effect of Curcumin on chemotherapy-induced intestinal dysfunction in rats. METHODS: Sixty healthy Wistar rats were randomly divided into control group (normal saline), 5 FU group and 5-FU+Curcumin group. The weight, serum level of endotoxin, DAO and D lactate were determined. The pathological change of intestinal mucosa structure was studied under light microscopy and electron microscopy. The expression of Bax, Bcl-2 and Caspase-3 were assessed by immunohistochemical staining. RESULTS: The Curcumin intragastrically administrated obviously reduced 5-FU-induced weight loss. 5-FU induced dramatic increase of serum endotoxin, D-lactate and D-Amino Acid Oxidase (DAO) that were significantly reversed by Curcumin treatment. Meanwhile, 5-FU-induced-damage to intestinal mucosa structure was markedly recovered by Curcumin. The expression of Bax and Caspase-3 were dramatically increased after 5-FU treatment (p<0.01) and Curcumin treatment significantly reduced Bax expression (p<0.05) but had only a moderate effect on reducing caspase-3 expression (p>0.05). Interestingly, Bcl-2 expression was low in control group but increased after 5-FU treatment (p>0.05) and Curcumin treatment further stimulated Bcl-2 expression (p<0.05). CONCLUSIONS: Curcumin can significantly reverse chemotherapy-induced weight-loss, increase of serum endotoxin, D-lactate and DAO and damage to intestinal mucosa structure. Curcumin also reduced the expression of pro-apoptotic Bax but stimulated anti-apoptotic Bcl-2 to attenuate 5-FU-induced apoptosis of intestinal epithelial cells. The clinical administration of Curcumin may improve chemotherapy-induced intestinal dysfunction, thus increasing the clinical efficacy of chemotherapy. PMID- 24228096 TI - Spermatocytic seminoma: a 21 years' retrospective study in a tertiary care hospital in Pakistan. AB - BACKGROUND: Spermatocytic seminoma is a rare testicular germ cell tumor of old men. Accounting for 1-4% of all seminomas, spermatocytic seminomas have distinct pathogenesis, histological features, immunohistochemical profile and comparatively benign clinical behavior which distinguishes them from other germ cell tumors, especially classic seminoma. AIMS: The purposes of our study were to assess the patient demographics, pathological features and to evaluate the utility of CD 117 immunostain along with other immunohistochemical stains in distinguishing Spermatocytic seminomas from classic seminomas. MATERIAL AND METHODS: All spermatocytic seminomas patients diagnosed during 1992 to 2013 at Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University hospital were included. Patient characteristics, histological details and follow-up data of few patients were available. CD 117 expression was determined by immunohistochemistry. RESULTS: Total 16 cases of Spermatocytic seminomas were reviewed. Median age was 60 years and average tumor size was 10.4 cms. Microscopically, all of the 16 cases showed presence of edema and absence of lymphocytic infiltrate and intratubular germ cell neoplasia. Cytoplasmic glycogen was negative in all 13 cases, PLAP immunostain was negative in all 12 cases, while CD 117 was positive in all 8 cases, where applied. CONCLUSION: CD 117 is of limited utility in differentiating the spermatocytic seminoma from classic seminoma as it is expressed in significant number of spermatocytic seminomas. However, different histological features, PAS special stain and PLAP immunostain are significantly helpful in distinguishing these two entities. PMID- 24228097 TI - SIRT1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration. AB - Brain metastases are a frequent and ongoing major complication of non-small cell lung cancer (NSCLC). To deepen our understanding to the underlying mechanisms by which NSCLC cells metastasize to brain and hence to improve the therapy, a high throughput RNAi screening with shRNA library of 153 epigenetic genes was subjected to A549, a NSCLC cell line with high migration ability, to examine the effects of these genes on cell migration by wound-healing assay. The screening results showed that knockdown of 2 genes (KDM5B and SIRT1) dramatically and specifically inhibits A549 migration but not affects the proliferation, which was subsequently confirmed through transwell migration assay. Furthermore, SIRT1 is found to be highly expressed in brain metastasis tissues of NSCLC, compared to the NSCLC tissues, suggesting that SIRT1 may play roles in brain metastasis of NSCLC. The relationship between SIRT1 expression and cell migration ability was further investigated in three NSCLC cell lines and the result indicated that SIRT1 expression is tightly correlated with cell migration ability. Collectively, our work provides potential biomarker and therapeutic target for brain metastasis of NSCLC. PMID- 24228098 TI - Administration of dexamethasone protects mice against ischemia/reperfusion induced renal injury by suppressing PI3K/AKT signaling. AB - Dexamethasone (DEX), a ligand for glucocorticoid receptor (GR), has long been used in the clinical practice due to its anti-inflammatory and immunosuppressive properties. Given that ischemia/reperfusion (IR)-induced renal injury is featured by the excessive immune response; the current study is therefore designed to address the impact of dexamethasone on IR-induced renal injury, a common disorder in the clinical settings. Precondition of mice with 4 mg/kg of dexamethasone significantly attenuated IR-induced injury as manifested by the improved renal function along with ameliorated pathological changes and suppressed inflammatory infiltration. Mechanistic studies revealed that dexamethasone promotes GR activation, and by which it attenuates the signals for PI3K/AKT activation. Attenuated PI3K/AKT signaling thus suppresses inflammatory response which then protects kidneys from IR-induced injury. All together, our data support that dexamethasone could be a good alternative therapy for prevention and treatment of IR-induced renal injury in the clinical practice. PMID- 24228099 TI - FasL on human nucleus pulposus cells prevents angiogenesis in the disc by inducing Fas-mediated apoptosis of vascular endothelial cells. AB - The intervertebral disc is the largest avascular organ in the human body. However, with the progress of intervertebral disc degeneration (IDD), the disc tends to be vascularized increasingly via angiogenesis. It is well established that both human nucleus pulposus (NP) cells and vascular endothelial cells express FasL and Fas. However, the issue remains open as to whether there are certain active mechanisms preventing angiogenesis in the disc via the FasL-Fas machinery. Here, we established a co-culture system of human NP cells and vascular endothelial (HMEC-1) cells. We found that normal NP cells were more capable of inducing apoptosis in HMEC-1 cells (14.2+/-3.4%) than degenerate NP cells (6.7+/-1.9%), p<0.05. By up-regulating the FasL expression in degenerate NP cells, we found that FasL played an essential role in the mediation of HMEC-1 cell apoptosis with the activation of downstream FADD and caspase-3. Furthermore, we found an increased Fas expression in HMEC-1 cells following co-cultured with NP cells, which might be closely linked with FasL produced by NP cells and enhance their interaction. Collectively, this is the first study showing FasL-Fas network might plays an important role in the molecular mechanisms of angiogenesis avoidance of human disc. Consequently, our findings might shed light on the pathogenesis in human IDD and provide a novel target for the treatment strategies for IDD. PMID- 24228100 TI - Hemocoagulase atrox reduces vascular modeling in rabbit carotid artery adventitia. AB - OBJECTIVE: This study aimed to compare the effects of hemocoagulase atrox and cauterization hemostasis on intimal hyperplasia and explore the effect of hemocoagulase atrox on vascular modeling in rabbit carotid artery adventitia. METHODS: A total of 27 rabbits were randomly divided into 3 groups (0d, 14d, 28d). They were anaesthetized using an intramuscular injection of phenobarbital sodium (1 ml/kg). The left and right common carotid arteries were exposed and capillary hemorrhaged after blunt dissection of the adventitia layers of common carotid arteries. Nine rabbits in each group were again randomly divided into 3 groups, in which animals were respectively treated with hemocoagulase (2 U/ml), cauterization (power = 40 w) and saline (as control). Groups of animals were euthanized at 0, 14 and 28 days after surgery. The samples were equally divided in the middle of the adventitia removal section to obtain equal parts for histologic, immunohistochemical and molecular biologic analysis. The vascular repair after adventitial stripping was observed by HE staining, Masson staining and transmission electron microscopy. The expression of carotid MCP-1, PCNA, TGF beta1, alpha-SMA and VEGF were measured at different time points by RT-PCR and immunohistochemical staining. RESULTS: HE staining and Masson staining showed that hemocoagulase atrox had a significantly stronger effect on reducing intimal hyperplasia than the cauterization after 14 and 28 days. The results of RT-PCR showed that the expression of MCP-1, TGF-beta1, alpha-SMA and VEGF in hemocoagulase atrox-treated animals were lower than that of cauterization-treated animals. CONCLUSION: Our results suggested that hemocoagulase atrox as a topical hemostatic is safety and efficiently and it can accelerate adventitia restoration and decrease intimal proliferation. PMID- 24228101 TI - Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry. AB - Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. PMID- 24228102 TI - DGKalpha DNA vaccine relieves airway allergic inflammation in asthma model possibly via induction of T cell anergy. AB - Induction of T cell immune tolerance is thought to be a good method for treatment of asthma. Diacylglycerol kinases alpha (DGKalpha), enzymes that catalyze phosphorylation of diacylglycerol to produce phosphatidic acid, could inhibit diacylglycerol (DAG)-mediated signaling following T-cell receptor engagement and prevent T cell hyperactivation, thus playing important roles in the induction of T cell anergy. In the present study, we aimed to investigate the effects of DNA vaccine encoding DGKalpha gene administration on allergen-induced airway allergic inflammation in the murine model of asthma. Animal models were created and plasmid containing DGKalpha were constructed. Cytokine production was detected after the administration of DGKalpha gene plasmid. Immunization of mice with alum adsorbed ovalbumin (OVA) followed by challenged with inhalation of aerosolized OVA resulted in the development of airway allergic inflammation. Administration of DGKalpha gene before the aerosolized OVA challenge significantly decreased the allergic airway inflammation and eosinophil infiltration in bronchoalveolar lavage fluid (BALF). Immunization with DGKalpha DNA vaccine decreased OVA specific IgE and interleukin 13 (IL-13) levels in sera, and increased the IFN gamma level in BALF. The results of the present study provide evidence for the potential utility of the administration of DGKalpha DNA vaccine as an approach to gene therapy for asthma. PMID- 24228103 TI - In vivo biocompatibility of the PLGA microparticles in parotid gland. AB - Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID- 24228104 TI - Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung. AB - Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as an enzyme in reducing 5alpha-dihydrotestosterone (5alpha-DHT) to 5alpha androstane-3alpha, 17beta-diol (3alpha-diol) and oxidizing 3alpha-diol to androsterone. It was subsequently demonstrated to possess ketosteroid reductase activity in metabolizing other steroids including estrogen and progesterone, 11 ketoprostaglandin reductase activity in metabolizing prostaglandins, and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. AKR1C3 was demonstrated in sex hormone-dependent tissues including testis, breast, endometrium, and prostate; in sex hormone-independent tissues including kidney and urothelium. Our previous study described the expression of AKR1C3 in squamous cell carcinoma and adenocarcinoma but not in small cell carcinoma. In this report, we studied the expression of AKR1C3 in normal tissue, adenocarcinomas (43 cases) and neuroendocrine (NE) tumors (40 cases) arising from the aerodigestive tract and pancreas. We demonstrated wide expression of AKR1C3 in superficially located mucosal cells, but not in NE cells. AKR1C3-positive immunoreactivity was detected in 38 cases (88.4%) of adenocarcinoma, but only in 7 cases (17.5%) of NE tumors in all cases. All NE tumors arising from the pancreas and appendix and most tumors from the colon and lung were negative. The highest ratio of positive AKR1C3 in NE tumors was found in tumors arising from the small intestine (50%). These results raise the question of AKR1C3's role in the biology of normal mucosal epithelia and tumors. In addition, AKR1C3 may be a useful adjunct marker for the exclusion of the NE phenotype in diagnostic pathology. PMID- 24228105 TI - High expression of Notch ligand Jagged2 is associated with the metastasis and recurrence in urothelial carcinoma of bladder. AB - BACKGROUND: The Notch signaling pathway is closely related with human organ development and tumorgenisis. Jagged2 is among the most popular topic in Notch studies currently. Recent studies found its vital role in tumor metastasis in breast cancer; however, its expression profile and its prognostic value in urothelial carcinoma of bladder have not been investigated. METHODS: Immunohistochemistry was used to detect the expression of Jagged2 in 120 bladder urothelial carcinoma. Moreover, the expression of Jagged2 was analyzed by Western blot in 60 bladder urothelial carcinoma and 20 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of GSIXX (the inhibitor of Jagged2). Prognostic value of Jagged2 expression and its correlation with tumor metastasis and recurrence were evaluated, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells were detected as well. RESULTS: There was a significantly higher Jagged2 expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Jagged2 expression was positively correlated with histological grade, p T stage, recurrence, and metastasis. With the increasing concentration of GSIXX, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage. CONCLUSIONS: Jagged2 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Jagged2 played an important function on the bladder cancer cells' proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer. PMID- 24228106 TI - Cyclosporin A enhances the ability of trophoblasts to displace the activated human umbilical vein endothelial cell monolayers. AB - Transformation of the spiral arteries including the displacement of vascular endothelial cells by extravillous trophoblasts is an essential prerequisite to normal placentation. However, the activated endothelial cells resist the invasion of trophoblasts, which contributes to the pathologies of some pregnant disorders. Our previous studies have demonstrated that Cyclosporin A (CsA) promotes the migration and invasion of human first-trimester trophoblasts. In the present study, we further investigated whether CsA could promote the ability of trophoblasts to displace the activated human umbilical vein endothelial cell (HUVEC) monolayers and the possible molecular mechanisms. Human choriocarcinoma Jar cells were used as a model of invasive trophoblasts. CsA pretreated JAR cells (red) were added to HUVEC monolayers (green) activated with either necrotic JAR cells or tumor necrosis factor alpha (TNFalpha). The ability of JAR cells to displace HUVECs from the monolayers was examined by confocal microscopy. The effects of CsA on Titin and E-cadherin expression, matrix metalloproteinases (MMPs) activity and CXCL12 secretion of JAR cells were evaluated by western blot, gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. We found that CsA pretreatment increased the ability of JAR cells to displace activated HUVECs from the monolayers. However, the displacement was reduced by untreated JAR cells. Moreover, CsA pretreatment up-regulated Titin expression, down-regulated E-cadherin expression, improved MMP2 and MMP9 activity, and increased the CXCL12 secretion in JAR cells. These results indicate that CsA may improve the trophoblast invasion to activated HUVEC monolayers through different downstream targets, and ultimately, improve the transformation and remodeling of spiral arteries. PMID- 24228107 TI - Proteomic analysis of knock-down HLA-G in invasion of human trophoblast cell line JEG-3. AB - Previous studies showed that aberrant HLA-G expression in trophoblast cells plays important roles in trophoblast invasion; however, the mechanisms remain to be explored. In this study, we found that suppressed HLA-G expression could dramatically decrease the mRNA and protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9, and in the proteome assay, there were 3 identified proteins namely, prefoldin 1, eukaryotic translation elongation factor 2 and malate dehydrogenase 2, which were verified by Western blot and known to be associated with invasion, cell cycle and cell metabolism, respectively. Collectively, our study indicated a potential involvement of HLA-G in autocrine networks that may regulate prefoldin, MMPs and trophoblast invasion at the maternal-fetal interface in human pregnancy. PMID- 24228108 TI - ZFX knockdown inhibits growth and migration of non-small cell lung carcinoma cell line H1299. AB - ZFX (zinc finger transcription factor, X chromosome-linked) contributes to the maintenance of different types of stem cells and the progression of various cancers. We have previously reported that ZFX knockdown inhibits proliferation of glioma in vitro and in vivo. Since overexpression of ZFX in lung cancer tissue correlates with lymph node metastasis, we hypothesized that ZFX may play a role in lung cancer. In this study, we identified ZFX as a promoter of lung cancer growth and migration in a NSCLC (non-small cell lung carcinoma) cell line H1299. ZFX knockdown caused proliferation inhibition determined by MTT assay and colony formation assay, G0/G1 arrest of cell cycle and slightly increased proportion of apoptotic cells assessed by flow cytometry assay, decreased population of migrating cells showed by wound-healing assay, increased cell senescence evidenced by senescence-associated beta-galactosidase staining. ZFX knockdown also led to decreased proportion of tumor bearing mice and reduced mean tumor volume in a subcutaneous tumor model. In addition, western blot showed that ZFX knockdown down regulated a set of proteins involved in proliferation, survival and motility. Altogether, these results suggest that ZFX may be a potential therapeutic target for NSCLC. PMID- 24228109 TI - Correlation between platelet-derived growth factor signaling pathway and inflammation in desoxycorticosterone-induced salt-sensitive hypertensive rats with myocardial fibrosis. AB - OBJECTIVE: To investigate whether inflammation could excessively activate platelet-derived growth factor (PDGF) signaling pathway in desoxycorticosterone (DOCA) induced salt-sensitive hypertensive rats with myocardial fibrosis (MF). METHODS: A total of 30 male SD rats underwent right nephrectomy and then bred with 1% sodium chloride and 0.1% potassium chloride for 2 weeks. These animals were randomly divided into 3 groups: CON group, DOCA group and DOCA+FAS group. Systolic blood pressure (SBP) was measured once every 2 weeks; HE staining was done to observe myocardial inflammation; immunohistochemistry was done to detect expressions of monocyte-macrophage antigen (ectodermal dysplasia 1, ED-1), PDGFRalpha and PDGFRbeta in the myocardium; real time fluorescence quantitative PCR was employed to detect the mRNA expressions of DGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFRalpha and PDGFRbeta. RESULTS: The SBP in DOCA group and DOCA+FAS group increased markedly when compared with CON group (P<0.01), but there was no marked difference between DOCA group and DOCA+FAS group (P>0.05). At 14 days, in DOCA group, the myocardial inflammation was obvious, ED-1 expression increased markedly, the mRNA expressions of PDGF-A, PDGF-B, PDGF-C, PDGFRalpha and PDGFRbeta increased to different extents, protein expressions of PDGFRalpha and PDGFRbeta also elevated markedly (P<0.01), but the PDGF-D mRNA expression remained unchanged, when compared with CON group. After treatment with fasudil (a drug with anti-inflammatory activity), myocardial inflammation was significantly attenuated, mRNA expressions of PDGF-A, PDGF-B, PDGF-C and PDGFRalpha as well as PDGFRalpha protein expression reduced dramatically (P<0.01), but the mRNA and protein expressions of PDGFRbeta remained unchanged (P>0.05) when compared with DOCA group. CONCLUSION: In DOCA/salt induced hypertensive rats with MF, excessive activation of PDGF/PDGFR signaling pathway is involved in myocardial inflammation. PMID- 24228110 TI - Diagnostic and therapeutic implications of a novel immunohistochemical panel detecting duodenal mucosal invasion by pancreatic ductal adenocarcinoma. AB - BACKGROUND: We investigated a series of pancreaticoduodenectomy and duodenal biopsies with a panel of immunohistochemical markers to identify duodenal mucosal invasion by pancreatic ductal adenocarcinoma (PDAC), including markers of poor prognosis and targets of promising novel immunotherapies. MATERIALS AND METHODS: Eighteen consecutive pancreaticoduodenectomy specimens with duodenal mucosal invasion by PDAC were examined for expression of MUC1, MUC4, MUC5AC, MUC6, mesothelin, MUC2, CDX2, and DPC4 on formalin-fixed, paraffin-embedded sections of duodenal-ampullary-pancreatic junctions. Expression of all but MUC6 was also assessed in duodenal biopsies from 12 patients with duodenal mucosal invasion by PDAC. RESULTS: The duodenal mucosa expressed MUC1 (crypts), MUC2 (goblet cells), MUC6 (Brunner glands), CDX2, and DPC4. PDACs in the duodenal mucosa from the resection (n=16-18) and biopsy (n=12) specimens were marked as follows: MUC1 100% (30/30), MUC4 83% (24/29), MUC5AC 83% (25/30), mesothelin 82% (23/28), MUC2 7% (2/30), and CDX2 36% (10/28). Loss of DPC4 expression was seen in 16 of 29 (55%) cases. Reactive mucosa adjacent to PDAC expressed MUC4, MUC5AC and mesothelin in 65% (17/26), 19% (5/27), and 19% (5/26) of cases, respectively. While MUC5AC and mesothelin had high diagnostic accuracy for detection of PDAC, MUC2, CDX2 and DPC4 expression demonstrated negative correlation with PDAC, with absent expression being highly specific for PDAC. CONCLUSION: Immunohistochemical labeling for PDAC biomarkers may aid the diagnosis of PDAC in duodenal biopsy, especially in situations where diagnosis of a pancreatic mass is challenging. PMID- 24228111 TI - Effect of GnRH-II on the ESC proliferation, apoptosis and VEGF secretion in patients with endometriosis in vitro. AB - OBJECTIVE: To study the effect of GnRH-II on the cell proliferation, apoptosis and secreting vascular endothelial growth factor (VEGF) of ectopic, eutopic and normal endometrial stromal cells (ESC) from patients with or without endometriosis (EMs) in vitro. METHODS: The ectopic, eutopic and normal ESC were isolated, cultured and identified, then added 0 M, 10(-10) M, 10(-8) M, 10(-6) M GnRH-II. The growth and proliferation of three ESC were measured by MTT assay; the cell apoptosis were detected with the method of Hoechst staining and Flow Cytometry test; ELISA was used to measure the VEGF concentration change by three ESC secretion. RESULTS: GnRH-II inhibited the proliferation of ectopic, eutopic ESC from patients with endometriosis and normal ESC from control patients, in a dose- and time-dependent manner (P<0.05); GnRH-II increased the apoptotic rate of three ESC in a dose-dependent manner (P<0.05); The concentration of VEGF in three ESC was significantly decreased after the treatment of GnRH-II, in a dose dependent manner (P<0.01); And these above effects were the strongest on the ectopic than on the eutopic or normal, there were statistical significance (P<0.05); and three was no significantly difference between the eutopic and normal (P>0.05). CONCLUSIONS: GnRH-II significantly inhibited the cell proliferation, induced cell apoptosis and decreased the VEGF secreting of ectopic, eutopic and normal ESC in EMs in vitro, and these effects were the strongest on ectopic ESC, which suggested that GnRH-II may become a new effective treatment for endometriosis. PMID- 24228112 TI - High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma. AB - Biglycan (BGN), an extracellular matrix component, has been reported to play a crucial role in the tumor progression of various cancers. However, the relation between the expression of BGN and clinical prognosis has not been studied yet. We therefore carry out the present study to elucidate the role of BGN in predicting outcomes of patients with esophageal squamous cell carcinoma (ESCC). In this study, the expression of BGN in 170 cases of ESCC tissues and matched 46 adjacent non-tumorous tissues was measured by quantitative real-time PCR and immunohistochemistry. Upregulation of BGN occurred in approximately 60% of primary ESCCs compared with their non-tumor counterparts. In addition, high expression of BGN was significantly associated with clinical stage (P = 0.009), tumor invasion (P = 0.006) and lymph node metastasis (P = 0.046). The 5-year disease-specific survival (DSS) in high expression of BGN group is poorer than that in low level expression group (36.8% VS 57.4%, P = 0.006). Stratified analysis according to the pathological stage revealed its discernibility on DSS was only pronounced in patients with advanced clinical stage (P = 0.010). Cox multivariate analysis revealed that pathologic N category (P < 0.001; hazard ratio, 2.482, 95% CI, 1.576-3.909) and BGN expression (P = 0.019; hazard ratio, 1.713, 95% CI, 1.092-2.688) were two independent prognostic factors. The findings of the present study provide evidence that BGN represents a potential novel prognostic biomarker for resected ESCC patients in advanced clinical stage. PMID- 24228113 TI - Systemic mesenchymal stem cells reduce growth rate of cisplatin-resistant ovarian cancer. AB - Epithelial ovarian cancer is one of the most malignant cancers in women and resistant to chemotherapy is the major obstacle for the five-year survival rate. Cisplatin is one of the effective anticancer drug used in the ovarian cancer. To find a good strategy to cure the tumors which is resistant to cisplatin, the cisplatin-resistant 3SKOV3 cells were selected from SKOV-3 ovarian cancer cells. Furthermore, the isolated mesenchymal stem cells were infused systemically to try to cure the transplanted tumor induced by 3SKOV3 cells in nude mice. The morphology and cell membrane CD44 expression were investigated by microscope and flow cytometry. The biological behaviors of resistant 3SKOV3 and its parental SKOV3 cells, including proliferation, adhesion, and cell cycle were determined by CCK8, absorbance assay and FCM methods. The transplanted tumors were set up in nude mice with 3SKOV3 cells injection. The growth rate of transplanted tumors was detected following with MSCs injection. The 3SKOV3 cells have different morphologic manifestation and expressed high level of CD44 molecule. At the same time, 3SKOV3 cells have less adhesion ability and less S-phase ratio. The isolated MSCs from bone marrow could inhibit the growth of transplanted tumor via systemic injection. The cisplatin-resistant 3SKOV3 cells have the different biological behaviors as its parental SKOV3 cells. The present study indicated that systemic MSCs have the therapeutic role on ovarian cancer. However, further investigations are in progress to elucidate the underlying mechanism. PMID- 24228114 TI - High expression of inositol polyphosphate phosphatase-like 1 associates with unfavorable survival in hepatocellular carcinoma. AB - Inositol polyphosphate phosphatase-like 1 (INPPL1), also known as SH2-containing inositol 5'-phosphatase 2 (SHIP2), has been suggested to act downstream of the PI3K/AKT pathway and play an important function in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to determine its clinicopathologic significance in hepatocellular carcinoma (HCC) have not been investigated. In the present study, one-step quantitative PCR reverse transcription-polymerase chain reaction (qPCR) and immunohistochemistry (IHC) analysis with HCC tissue microarrays (TMA) were employed to evaluate the expression of SHIP2 in HCC. The results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in HCC tissue than in corresponding non-cancerous tissue (p = 0.0014 and p < 0.001, respectively). The expression of SHIP2 protein in HCC was related to tumor differentiation, alpha-fetoprotein level, liver cirrhosis, and five-year survival rate (all p < 0.05). Kaplan-Meier method and log-rank test indicated that high expression of SHIP2 (p = 0.017) and tumor differentiation (p = 0.036) showed significant correlations with poor prognosis of HCC patients. The data indicate that SHIP2 expression is correlated with significant characteristics of HCC, and it may be useful as an unfavorable prognostic factor in HCC. PMID- 24228115 TI - Hepatorenal syndrome: insights into the mechanisms of intra-abdominal hypertension. AB - OBJECTIVE: Hepatorenal syndrome is one of the serious complications of cirrhosis and closely associated with the increasing intra-abdominal pressure (IAP). The study aims to explore the potential mechanism of intra-abdominal hypertension in the development of hepatorenal syndrome in mouse models. METHODS: Eighty male mice were randomly divided into model group (subcutaneous injection of carbon tetrachloride) and control group (subcutaneous injection of olive oil). After 12 weeks, parts of the mice were sacrificed and liver histopathology was detected. Then, albumin (30 g/L) and normal saline were separately injected into the peritoneal cavity of mice to induce the different IAP levels (0, 5, 10 and 20cmH2O). Blood urea nitrogen, serum creatinine and renal histopathology were examined 24 hours later. RESULTS: Blood urea nitrogen and serum creatinine levels were statistically significant high in the group of IAP= 10 and 20cmH2O as compared with the IAP= 0cmH2O. From results of renal histopathology, the constrictive renal tubular lumen and inflammatory infiltration in the interstitial were observed in groups of IAP= 5 and 10cmH2O. Besides, the formed casts and hyperemia in the renal interstitial could be detected in group of IAP= 20cmH2O. The cellular swelling and edema of renal tubular epithelial cells were found in model group simultaneously. CONCLUSIONS: Our study suggested that intra abdominal hypertension was a significant pathological mechanism and a potential independent risk factor of hepatorenal syndrome. PMID- 24228116 TI - An improved method for the isolation and culture of rat epidermal stem cells. AB - The management of burns and injuries using novel treatment strategies involving epidermal stem cells (ESC) requires a better understanding of the biology of these cells, in particular, their isolation and the maintenance of their unique characteristics in culture. The purpose of this study was to describe an improved method for isolating putative ESC from fetal rat skin and to maintain them long term in culture. Single ESC suspensions were obtained from fetal rat skin by enzyme digestion containing 0.5% neutral protease. The target cells were harvested by rapid adherence on type IV collagen plates and were cultured in complex DMEM. After primary isolation, cells were continuously cultured in K serum free medium. After reaching 70-80% confluence, the cells were digested with 0.25% trypsin at 37 degrees C for 5-10 minutes, and passaged at a ratio of 1:2. The cultured ESC showed good growth, resulting in cell viability of over 98%. Four days later, clones containing 100-200 cells were detected, showing cobblestone-like characteristics. The rapidly adherent cells were positive for keratin 15, 19 and P63. Eighty three percent of cells expressed beta1 integrin. The growth-curve showed that the rapidly adherent cells were in the exponential growth phase. The protocol described in this paper provides a simplified and effective method to isolate and maintain long-term culture of epidermal stem cells from fetal rat skin. This method should be valuable for isolating and studying ESC from various transgenic rat lines that are currently available. PMID- 24228117 TI - Loss of RhoGDI is a novel independent prognostic factor in hepatocellular carcinoma. AB - RhoGDI (Rho GDP-dissociation inhibitor alpha or RhoGDIalpha) has been identified as a regulator of Rho GTPases, which are essential for tumor progression, but its role in cancer remains controversial and little is known in hepatocellular carcinoma (HCC). Using immunohistochemistry, we analyzed RhoGDI expression in 147 clinicopathologically characterized HCC cases. RhoGDI expression was detected in cytoplasm of HCC tissues. Statistical analysis showed that there was no relationship between RhoGDI expression and clinicopathological features. Importantly, a significant trend was identified between loss of RhoGDI expression in HCC and worsening clinical prognosis. Multivariate survival analysis showed that negative RhoGDI expression was recognized as an independent prognostic factor of patient's survival. Our results suggest that RhoGDI protein is a valuable marker of prognosis for patients with HCC. PMID- 24228118 TI - High frequency of coexpression of maspin with p63 and p53 in squamous cell carcinoma but not in adenocarcinoma of the lung. AB - Maspin, a member of the serpin family of protease inhibitors, has been shown to inhibit tumor growth and suppress metastasis in several malignancies, including lung cancer. Previous studies have reported that p63 and p53 control maspin expression by transactivating the promoter. The present study analyzed immunohistochemical studies to determine the expression and coexpression patterns of maspin, p63 and p53 in non-small cell lung carcinoma, specifically squamous cell carcinoma and adenocarcinoma. The results showed that 83/86 cases (96.5%) of squamous cell carcinoma and 82/161 cases (50.9%) of adenocarcinoma included in this study were positive for maspin. There were 79/86 cases (91.9%) of squamous cell carcinoma and 16/161 cases (9.9%) of adenocarcinoma with positive expression for p63. In addition, 77/86 cases (89.5%) of squamous cell carcinoma and 99/161 cases (61.5%) of adenocarcinoma were positive for p53. Maspin, p63 and p53 expression were each significantly higher in squamous cell carcinoma than adenocarcinoma. Squamous cell carcinomas more highly coexpress maspin and p63, as well as maspin and p53, when compared with adenocarcinomas. The high frequency of coexpression of maspin and p63, as well as maspin and p53, in squamous cell carcinoma, suggests that p63 and p53 may be involved in the pathway to control maspin expression. Therapeutic targeting on maspin, p63 and p53 molecules might be beneficial in the management of patients with squamous cell carcinomas of the lung in the future. PMID- 24228119 TI - CTLA-4 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease. AB - OBJECTIVE: The aim of this study was to investigate whether four single nucleotide polymorphisms (SNPs) in CTLA-4 gene are associated with chronic obstructive pulmonary disease (COPD) in a Chinese population. METHODS: Samples were collected from a Chinese population and analyzed for the association of SNPs in CTLA-4 gene with COPD in a case-control study. Four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were chosen and genotyped. The results were then analyzed using statistical methods. RESULTS: We found that none of these four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were associated with the disease. CONCLUSION: Our data suggested that there was no significant association between these four SNPs in CTLA-4 gene and COPD susceptibility in a Chinese population. PMID- 24228120 TI - Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer. AB - OBJECTIVE: To investigate chemoresistance of human gastric cancer to chemotherapeutic drugs in vitro and explore the relationship with Bcl-2 protein expression. METHODS: Single-cell suspensions were prepared from freshly excised samples of primary gastric cancer, and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. The induction of cell death was confirmed by microscopic analysis of cell morphology. Metabolic activity and the inhibitory rate (IR) of cells were evaluated by MTT assay. Expression of Bcl-2 was determined by immunohistochemistry of gastric cancer tissue samples. RESULTS: The IRs of cancer cells exposed to different chemotherapeutic drugs varied as follows: the IRs for TAX, CDDP and 5-FU were significantly higher than those for ADM and MMC (P < 0.01). Poorly differentiated gastric cancer cells were more sensitive than well differentiated cells (P = 0.021). The positive rate of Bcl-2 expression was 80%, and Bcl-2 expression was significantly associated with chemoresistance to 5-FU (r(s) = 0.265, P = 0.041), ADM (r(s) = 0.425, P = 0.001) and MMC (r(s) = 0.40, P = 0.002). Furthermore, Bcl-2 expression was strongly associated with lymph node metastasis in gastric cancer (P = 0.009). CONCLUSION: Overexpression of Bcl-2 may predict a loss of the efficacy of the chemotherapy drugs 5-FU, ADM and MMC in patients with gastric cancer. PMID- 24228121 TI - Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma. AB - IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4 related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4 related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder. PMID- 24228123 TI - Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature. AB - Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney. PMID- 24228122 TI - Extranodal Rosai-Dorfman disease involving appendix and mesenteric nodes with a protracted course: report of a rare case lacking relationship to IgG4-related disease and review of the literature. AB - Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare disease of unknown etiology that typically presents as nodal disease in young children. However, it also can present in various extranodal sites and can be difficult to recognize if not considered in the differential diagnosis. Here, we report a case of appendix involvement by extranodal RDD, which occurred in a 69-year-old woman with a long duration of 12 years for intermittent right lower quadrant pain. The patient underwent a right hemicolectomy for a clinical diagnosis of appendiceal cancer. A mixed inflammatory infiltration of mature lymphocytes, plasma cells and histiocytes exhibiting emperipolesis were indentified. Other areas had storiform fibrosis and sclerosis admixed with numerous plasma cells. These histologic features combination with immunoreactivity for CD68 and S100 protein were indicative of a diagnosis of extranodal RDD. We discuss the clinical, pathologic findings as well as differential diagnoses and consideration of a possible relationship of this entity to IgG4-related lesion. PMID- 24228125 TI - Prominent mucoid degeneration of the parotid gland in a patient with systemic lupus erythematosus. AB - Lupus erythematosus (LE) can cause various cutaneous lesions including panniculitis (LE profundus), but salivary gland involvement has been extremely rare in patients with LE. Herein, we report the first documented case of systemic LE with prominent mucoid degeneration and lymphoplasmacytic infiltration in the parotid gland. A 38-year-old Japanese male with histories of autoimmune hemolytic anemia and systemic LE presented with a swelling of the bilateral cervical region. A physical examination revealed a swelling of the bilateral parotid gland and erythema of the right cheek. A biopsy specimen of the cheek demonstrated LE profundus with mucoid material deposition in the dermis. A biopsy specimen of the parotid gland showed lymphoplasmacytic infiltration and prominent mucoid material deposition within the parotid gland as well as mild lymphoplasmacytic infiltration and hyaline fat necrosis in the perisalivary tissue. Mucoid material deposition is one of the characteristic features of LE, however, this is the first case demonstrating mucoid material deposition in the salivary gland. Moreover, albeit extremely rare, lymphoplasmacytic infiltration within the lobules of the salivary gland has also been reported in patients with LE. Therefore, it is important that both lymphoplasmacytic infiltration and mucoid material deposition must be included in the differential diagnostic considerations for salivary gland tumors in patients who had been previously diagnosed as systemic or discoid LE. PMID- 24228124 TI - A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma. AB - Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results. PMID- 24228126 TI - Mucinous bronchioloalveolar carcinoma with K-ras mutation arising in type 1 congenital cystic adenomatoid malformation: a case report with review of the literature. AB - Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare hamartomatous cystic lesion, characterized by the presence of large cysts, which are histopathologically lined by pseudostratified ciliated cells. It has been recognized that rare cases of type 1 CCAM show malignant transformation, usually bronchioloalveolar carcinoma (BAC) or adenocarcinoma. Herein, we describe a case of BAC arising in type 1 CCAM with K-ras mutation. A 9-year-old Japanese girl presented with fever. Computed tomography demonstrated large cystic lesions in her right lower lung. Histopathological study of the resected specimen revealed multiple cysts, which were lined by pseudostratified ciliated cells, and occasionally interspersed with mucous cells without atypia. A small focus of proliferation of columnar cells showing lepidic growth pattern was present. These columnar cells had abundant mucin in the cytoplasm and mildly to moderately enlarged nuclei. Accordingly, a diagnosis of BAC arising in type 1 CCAM was made. Polymerase chain reaction analysis revealed K-ras mutation at codon 12 in the BAC component. The presence of mucous cell/goblet cell hyperplasia and atypical adenomatous hyperplasia is a well known phenomenon in type 1 CCAM. A recent study clearly demonstrated K-ras mutation in these lesions, which are thought to be precursors of BAC. Therefore, the concept of malignant transformation in the sequence from type 1 CCAM to mucous cell hyperplasia to atypical adenomatous hyperplasia to BAC and invasive adenocarcinoma due to K-ras mutation has been proposed. Careful histopathological analysis is important for evaluation of malignant lesions in type 1 CCAM. PMID- 24228127 TI - Sustained complete remission of a limited-stage blastic plasmacytoid dendritic cell neoplasm followed by a simultaneous combination of low-dose DeVIC therapy and radiation therapy: a case report and review of the literature. AB - The patient was a 74-year-old man who was found to have a cutaneous mass on his left shoulder in February 2012. Because the mass bled easily and was tending to grow, total resection of the cutaneous tumor, which measured approximately 5 cm x 3 cm, was performed in July. Histopathological examination revealed a tumor that extended from the dermis to the cutaneous adipose tissue, but no invasion of the epidermis was seen. The tumor cells were plasmacytoid cells ranging in size from small to intermediate, and there was no nuclear irregularity. They had a high nuclear-cytoplasmic ratio, and nucleoli were observed. The tumor cells were CD4 positive, CD56-positive, and CD123-positive, and they were AE1/AE3-negative, CD3 negative, CD20-negative, and myeloperoxidase-negative. (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), a bone marrow examination, etc., were performed, but no lesions were detected at other sites. Based on the above findings a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN), Stage IEA, was made. Because the patient had limited-stage BPDCN and was elderly, we treated him with a simultaneous combination of low-dose DeVIC (dexamethasone, VP16, ifosfamide, and carboplatin) therapy and local radiation therapy (LRT) and sustained a complete remission for approximately 1 year. Simultaneous combination of non-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and LRT appeared to be useful in the treatment of limited-stage BPDCN even in the elderly. PMID- 24228128 TI - Histiocytoid breast carcinoma: a case report showing immunohistochemical profiles. AB - Histiocytoid breast carcinoma (HBC) is a rare type of breast cancer with a controversial histogenesis. Here we describe a case report of a 65-year old woman with HBC. The patient presented with two masses in the right breast. Histopathologically, the tumors consisted of a diffuse infiltration of large tumor cells and histological components of carcinoma in situ and atypical lobular hyperplasia were also observed. The infiltration pattern was similar to that of invasive lobular carcinoma with targetoid and Indian file arrangements. The invasive histiocytoid cells had finely granular, eosinophilic to vesicular cytoplasm and nuclei with a bland uniform appearance, a single small eosinophilic nucleolus and finely granular chromatin. We compared the immunohistochemical profiles of 17 breast cancer markers between invasive carcinoma, carcinoma in situ, atypical lobular hyperplasia and normal breast epithelium. Although they all shared the same reactivity for many of the proteins, they exhibited differences in GCDFP-15, E-cadherin, P120, CEA, HER-2, ER and PR expression, and these are discussed. This is the first case study of two HBC masses occurring in one breast simultaneously. By analyzing and comparing their morphologic characteristics and spectrum of immunohistochemical expression, our study supports the view that HBC is a variant of lobular carcinoma and our findings may assist in future diagnoses of HBC. PMID- 24228129 TI - Florid diffuse peritoneal deciduosis mimicking carcinomatosis in a primigravida patient: a case report and review of the literature. AB - A case of a 27 year old G1P0 female with a dichorionic, diamniotic twin pregnancy presenting with premature rupture of membranes found to have omental caking and diffuse yellow-tan peritoneal nodules, clinically suspicious for carcinomatosis. The case work-up showed this to be an example of florid-diffuse peritoneal deciduosis mimicking carcinomatosis which has since resolved 4 months postpartum. PMID- 24228130 TI - An adult case of systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder with good outcome. AB - Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disorder (EBV+T/NK LPD) encompasses a heterogeneous group of disorders that have a common feature with excessive lymphoid proliferation of mainly T cells and/or NK cells. This disease is rare, predominantly affects children and young adults, and associated with high mortality. Herein, we report a case of EBV+T/NK LPD that occurred in an old woman with good outcome. The patient presented with fever, splenomegaly, and pancytopenia. Computed tomography (CT) scan of the abdomen showed splenomegaly. The clinical impression was a malignant tumor of spleen, so splenectomy was performed. Microscopically, the architecture of the spleen was preserved. The white pulp Malpighian corpuscles were atrophied. The red pulp showed intact sinusoids and pulp cords with increased cellular infiltrate. The proliferating lymphoid cells were mostly small lymphoid cells with minimal or no nuclear atypia, mixed with rare medium-sized or large cells. Immunohistochemical study and in-situ hybridization showed that the EBER-positive lymphoid cells were positive for CD3 and CD56. They were also positive for cytotoxic molecules, such as T-cell restricted intracellular antigen (TIA1), granzyme B. The case exhibited polyclonal rearrangement of T-cell receptor gene (TCR) by polymerase chain reaction (PCR) studies. Without radiotherapy and chemotherapy, the patient is alive and well with no evidence of disease 25 months after surgery. PMID- 24228131 TI - Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review. AB - The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient's first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules. PMID- 24228132 TI - Anaplastic lymphoma kinase-positive large B-cell lymphoma: a case report with emphasis on the cytological features of the pleural effusion. AB - Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (ALK-positive LBCL) is an extremely rare distinct clinicopathological subtype of LBCL, characterized by the presence of ALK-positive monomorphic large immunoblast-like neoplastic B cells. Herein, we describe the first cytological report on ALK positive LBCL in the pleural effusion. A 69-year-old Japanese male with a past history of malignant lymphoma of the cecum presented with progressive dyspnea and pleural effusion. Removal of the pleural effusion and aspiration of bone marrow were performed. May-Grunwald-Giemsa stain of the pleural fluid revealed abundant single or small aggregates of large-sized round cells. These cells had centrally located large round to oval nuclei. The peculiar finding was the presence of pseudopodial cytoplasmic projections, and some neoplastic cells had eosinophilic pseudopodial cytoplasmic projections, which resembled "flaming plasma cells". Histopathological and immunohistochemical studies of the bone marrow demonstrated CD138(+), ALK1(+), CD20(-), CD79a(-), CD30(-), and IgA(+) large-sized neoplastic cells. Therefore, a diagnosis of ALK-positive LBCL was made. The peculiar finding of the present case was that most of the neoplastic cells had pseudopodial cytoplasmic projections, and some of them had eosinophilic pseudopodial cytoplasmic projections that resembled "flaming plasma cells", which has been recognized as the characteristic finding of IgA myeloma. Therefore, tumor cells that resembled "flaming plasma cells" in the pleural effusion may have had IgA in the cytoplasm. Albeit extremely rare, ALK-positive LBCL shows aggressive clinical course, thus, recognition of the cytomorphological features of this type of malignant lymphoma is important for early and correct diagnosis. PMID- 24228133 TI - Dubin-Johnson syndrome with multiple liver cavernous hemangiomas: report of a familial case. AB - Dubin-Johnson syndrome (DJS) is a rare autosomal recessive inheritance disorder of bilirubin metabolism. Herein we reported a complicated but interesting case which is readily resulted in misdiagnosis or an indefinite diagnosis, and this is the first reported familial case of DJS with multiple liver cavernous hemangiomas. A 49-year-old man was referred to our hospital for jaundice and multiple low-density liver masses. Extensive laboratory investigations showed conjugated hyperbilirubinaemia and positive urine bilirubin. Microscopically, lesions were composed of blood-filled vascular channels of various sizes lined by a single layer of flat endothelial cells supported by fibrous tissue. Coarse brown granules presented in the hepatocytes of the liver lobules locating beside the tumor, particularly in the centrilobular hepatocytes, and the granules showed blue-green with Schmorl's reaction lipofuscin staining. Interestingly, one of the patient's six siblings (female) shared the same condition with him. The relationship between DJS and hemangiomas remains unclear, and it might be contributed to some hereditary factors, or probably occurred simultaneously by chance. It was certified that the true reason for the long-term unclear jaundice was DJS, which was presumed clinically to be caused by bile excretion obstacles associated with the hemangiomas. Liver biopsy and histochemical stain may be helpful to identify the reason of jaundice and avoid misdiagnosis or an indefinite diagnosis. PMID- 24228134 TI - Sclerosing Sertoli cell tumor of the testis: a case report with review of the literature. PMID- 24228135 TI - Prognostic value of cancer stem cell marker CD133 expression in non-small cell lung cancer: a systematic review. AB - OBJECTIVE: To investigate the correlation between CD133-positive non-small cell lung cancer (NSCLC) and clinicopathological features and its impact on survival. METHODS: A search in the Pubmed, Embase and Wanfang databases (up to July 15, 2013) was performed. Only articles in which CD133 antigen was detected in situ localization by immunohistochemical staining were included. This meta-analysis was done using RevMan 5.2 software. Outcomes included overall survival and various clinicopathological features. RESULTS: A total of 1004 NSCLC patients from 11 studies were included. Meta-analysis showed that CD133 expression patients had a significant worse 5-year overall survival compared to the low expression ones (RR = 3.19, 95% CI: 2.05-4.98, P<0.0001 fixed random). With respect to clinicopathological features, CD133 expression by IHC method was closely correlated with tumor T stage (OR = 0.91, 95% CI: 0.59-1.39, P = 0.67 fixed-effect) and tumor grade (OR = 1.20, 95% CI: 0.80-1.79, P = 0.37 fixed effect). CONCLUSION: CD133-positive NSCLC patients had worse prognosis, and was associated with common clinicopathological poor prognostic factors. PMID- 24228136 TI - Cross-kingdom sequence similarities between human micro-RNAs and plant viruses. AB - Micro-RNAs regulate the expression of cellular and tissue phenotypes at a post transcriptional level through a complex process involving complementary interactions between micro-RNAs and messenger-RNAs. Similar nucleotide interactions have been shown to occur as cross-kingdom events; for example, between plant viruses and plant micro-RNAs and also between animal viruses and animal micro-RNAs. In this study, this view is expanded to look for cross-kingdom similarities between plant virus and human micro-RNA sequences. A method to identify significant nucleotoide sequence similarities between plant viruses and hsa micro-RNAs was created. Initial analyses demonstrate that plant viruses contain nucleotide sequences which exactly match the seed sequences of human micro-RNAs in both parallel and anti-parallel directions. For example, the bean common mosaic virus strain NL4 from Colombia contains sequences that match exactly the seed sequence for micro-RNA of the hsa-mir-1226 in the parallel direction, which suggests a cross-kingdom conservation. Similarly, the rice yellow stunt viral cRNA contains a sequence that is an exact match in the anti parallel direction to the seed sequence of hsa-micro-RNA let-7b. The functional implications of these results need to be explored. The finding of these cross kingdom sequence similarities is a useful starting point in support of bench level investigations. PMID- 24228137 TI - BRG1, a SWI/SNF chromatin remodeling enzyme ATPase, is required for maintenance of nuclear shape and integrity. AB - We recently reported that reducing the levels of BRG1, the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes, induces alterations in nuclear shape in a breast epithelial cell line. Immunostaining the BRG1 knockdown cells with nuclear lamina antibodies revealed a significantly increased frequency of grooves, or invaginations, in the nuclei. Disruption of each of the major cytoplasmic filament systems (actin, tubulin and cytokeratins) had no impact on the BRG1-dependent changes in nuclear shape, indicating that the observed changes in nuclear morphology are unlikely to be a result of alterations in the integrity of the nuclear-cytoplamic contacts in the cell. We propose that the BRG1 dependent nuclear shape changes reflect a role for the chromatin remodeling enzyme in maintaining the structural integrity of the nucleus via global regulation of chromatin structure and dynamics within the nucleus. PMID- 24228139 TI - Prediction of hypotension in spinal anesthesia. PMID- 24228138 TI - Neuroprotective effect of ginkgolide B on bupivacaine-induced apoptosis in SH SY5Y cells. AB - Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property. PMID- 24228140 TI - Intrathecal injection of magnesium sulfate: shivering prevention during cesarean section: a randomized, double-blinded, controlled study. AB - BACKGROUND: Regional anesthesia is known to significantly impair thermoregulation and predispose patients to hypothermia. We hypothesized that the addition of an intrathecal injection of magnesium sulfate (MgSO4) to bupivacaine would improve perioperative shivering in female patients undergoing elective caesarean section. METHODS: In a block-randomized, double-blinded, controlled trial 72 patients scheduled for elective caesarean section with spinal anesthesia were separated into two groups. In the treatment group, 2 ml of 0.5% bupivacaine plus 25 mg MgSO4 (0.5 ml) were injected intrathecally, and in the control group 2 ml of 0.5% bupivacaine plus 0.5 ml normal saline were injected intrathecally. Core temperature was measured before and after drug injection at predetermined intervals. Sedation was graded using the Ramsay sedation scale. RESULTS: No significant intergroup differences in appearance of shivering were seen immediately or at 5, 30, 40, 50, 60, and 90 min after block administration. However, at 10, 15, and 20 min post block, there was a significant difference in shivering. The group administered MgSO4 showed lower shivering grades compared with the control group. Core temperature was significantly reduced in the MgSO4 group compared to the normal saline group 30 min after blocking. CONCLUSIONS: Intrathecal injection of MgSO4 improved perioperative shivering in female patients undergoing elective caesarean section. PMID- 24228141 TI - The comparison of predictive performance in bispectral index prediction during target effect-site controlled infusion of propofol using different blood effect site equilibration rate constants in the same pharmacokinetic model. AB - BACKGROUND: Blood-brain equilibration rate constant (ke0 ) is derived from either pharmacokinetic and pharmacodynamic modeling (k e0_model) or a model-independent observed time to peak effect (k e0_tpeak). Performance in bispectral index (BIS) prediction was compared between k e0_model and k e0_tpeak for microemulsion or long chain triglyceride (LCT) propofol. METHODS: Time to peak effect (tpeak, time to a maximally reduced BIS value) of microemulsion propofol after an intravenous bolus (1 mg/kg) was measured in 100 patients (group Amicro). An observed tpeak of 1.6 min for LCT propofol was obtained from an earlier study. Another 40 patients received a target controlled infusions of microemulsion propofol (k e0_model = 0.187/min, group Bmicro = 20) or LCT propofol (k e0_model = 0.26/min, group BLCT = 20) and remifentanil. The k e0_tpeak's in group Bmicro and BLCT were calculated using the observed tpeak value obtained from group Amicro and 1.6 min, respectively. Effect-site concentrations of propofol were recalculated using the amounts of propofol infused over time and k e0_tpeak's. Predicted BIS values calculated by sigmoid Emax equations with k e0_model and k e0_tpeak were compared with observed BIS values during induction and emergence for both formulations of propofol. RESULTS: Observed tpeak of microemulsion propofol was 1.68 min. The median performance errors of BIS in group Bmicro were -1.83% (-24.8 to 18.9, k e0_model) and -2.42% (-26.1 to 36.2, k e0_tpeak), while 8.01% (-20.5 to 30.1, k e0_model) and 7.37% (-27.0 to 49.1, k e0_tpeak) in group BLCT. The median absolute performance errors of BIS in group Bmicro were 11.87% (2.2-31.1k e0_model) and 14.38% (-0.6 to 44.6, k e0_tpeak), while 17.31% (5.54-36.0, k e0_model) and 18.28% (-0.1 to 56.0, k e0_tpeak) in group BLCT. CONCLUSIONS: The k e0_model showed better performance in BIS prediction than the k e0_tpeak. PMID- 24228142 TI - Intubating laryngeal mask airway as an independent ventilatory and intubation device. A comparison between supine, right lateral and left lateral. AB - BACKGROUND: Sudden loss of airway in patients in the lateral position has always been proven to be difficult to manage with conventional laryngoscopy. We performed a randomized controlled trial to prove the success rate of ventilation and intubation in the lateral position via intubating laryngeal mask airway (ILMA). METHODS: Ninety patients were divided into three groups of 30 patients each, positioned supine, right lateral, and left lateral randomly. Each group comprised of both sexes of American Society of Anesthesiologists grade I and II, aged between 18-55 years with normal airway posted for surgery under general anesthesia. Patients were pre-medicated with fentanyl followed by induction with propofol and neuromuscular blockade with rocuronium. ILMA was inserted and blind tracheal intubation via ILMA was done. The success rate, time taken and the number of adjusting maneuvers used for both procedures were recorded. The data was tabulated and analyzed using ANOVA (analysis of variance), multiple 't' test and chi square. RESULTS: The success rate of intubation (96%) and time taken in insertion and intubation was found to be quite similar in all the three groups. CONCLUSIONS: We conclude that the ILMA has an important role to play in the emergency management of airways in patients in the lateral position in terms of ease, success rate and time taken. PMID- 24228143 TI - Effects of incrementally increasing tidal volume on the cross-sectional area of the right internal jugular vein. AB - BACKGROUND: Different tidal volume (TV) settings during mechanical ventilation alter intrathoracic blood volume, and these changes could alter central venous pressure and the cross sectional area (CSA) of the right internal jugular vein (RIJV). The aim of this study was to determine the optimal TV for maximizing the CSA of the RIJV in the supine and Trendelenburg positions in anesthetized patients. METHODS: Forty patients were randomly allocated to a supine group (Group S, n = 20) or a Trendelenburg group (Group T, n = 20) by computer generated randomization. RIJV CSAs were measured repeatedly after increasing the inspiratory volume in 1 ml/kg increments from a TV of 8 ml/kg to 14 ml/kg using ultrasound images. RESULTS: Peak inspiratory pressure increased significantly on increasing TV from 11 ml/kg to 14 ml/kg and between baseline (TV 8 ml/kg) and 11 ml/kg in both groups (P < 0.05). RIJV CSA was not increased versus baseline even after TV changes in either group and no intergroup difference was found. CONCLUSIONS: TV increases do not increase the CSA of the RIJV within the TV range 8 to 14 ml/kg in the supine or 10 degrees Trendelenburg position. PMID- 24228144 TI - Heart rate variability as a predictor of hypotension after spinal anesthesia in hypertensive patients. AB - BACKGROUND: Hypotension is a common phenomenon after spinal anesthesia in hypertensive patients. We investigated whether heart rate variability could predict the occurrence of hypotension after spinal anesthesia in hypertensive patients. METHODS: Forty-one patients undergoing spinal anesthesia were included. Heart rate variability was measured at five different time points such as before fluid loading (baseline), after fluid loading as well as 5 min, 15 min and 30 min after spinal anesthesia. Fluid loading was performed using 5 ml/kg of a crystalloid solution. Baseline total power and low to high frequency ratio (LF/HF) in predicting hypotension after spinal anesthesia were analyzed by calculating the area under the receiver operating characteristic curves (AUC). RESULTS: Moderate hypotension, defined as a decrease of mean arterial pressure to below 20-30% of the baseline, occurred in 13 patients and severe hypotension, defined as a decrease of mean arterial pressure greater than 30% below the baseline, occurred in 7 patients. LF/HF ratiosand total powers did not significantly change after spinal anesthesia. AUCs of LF/HF ratio for predicting moderate hypotension was 0.685 (P = 0.074), severe hypotension was 0.579 (P = 0.560) and moderate or severe hypotension was 0.652 (P = 0.101), respectively. AUCs of total power for predicting moderate hypotension was 0.571 (P = 0.490), severe hypotension was 0.672 (P = 0.351) and moderate or severe hypotension was 0.509 (P = 0.924), respectively. CONCLUSIONS: Heart rate variability is not a reliable predictor of hypotension after spinal block in hypertensive patients whose sympathetic activity is already depressed. PMID- 24228145 TI - Comparison of spread of subarachnoid sensory block and incidence of hypotension in early and late second trimester of pregnancy. AB - BACKGROUND: Obstetric or non-obstetric surgery can be performed in pregnant women during the second trimester. We evaluated maximal sensory block level (MSBL), and other sensory block characteristics after spinal anesthesia in early and late second trimester pregnant women. METHODS: Forty-four pregnant women scheduled for cervical cerclage under spinal anesthesia in the early second trimester (Group E) or in the late second trimester (Group L) were enrolled in this study. Spinal anesthesia was performed at the L3/4 and 7 mg of 0.5% hyperbaric bupivacaine was injected into the subarachnoid space. Hemodynamic variables, incidence of nausea/vomiting, ephedrine dose, and sensory block were recorded every 2.5 min during the first 15 min and 20 min after the injection. The MSBL, the time at which MSBL was achieved, and the time to the two-segment regression of the sensory level were also recorded. RESULTS: The maximum number of segments blocked was significantly greater in the Group L than in the Group E. The incidence of nausea/vomiting and hypotension, and dose of administrated ephedrine were significantly higher in the Group L than in the Group E. The mean arterial pressure during the 15 min after subarachnoid injection was significantly lower compared to the baseline value in the Group L. CONCLUSIONS: The MSBL of spinal anesthesia with hyperbaric bupivacaine 7 mg were T9 in the early and T5 in the late second trimester groups. Pregnant women in the late second trimester exhibited increased incidence of hypotension and need for ephedrine than women in the early second trimester. PMID- 24228146 TI - Plasma concentrations of nociceptin/orphanin FQ: comparison of levels after general and neuraxial anesthesia for arthroscopic knee surgery. AB - BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) is an endogenous opioid heptadecapeptide. Preclinically, the pharmacologic action of N/OFQ has been characterized for the treatment of pain in non-human primates. Clinically, the pharmacologic action of N/OFQ is unclear, and concentrations have only been measured under certain clinical conditions. The aims of this study were to measure the plasma concentrations of N/OFQ in different postoperative pain states and to identify the potential relationship between postoperative pain states and N/OFQ plasma concentrations. METHODS: Two groups of 14 patients scheduled for knee arthroscopy were included in this study. Postoperative pain in the first group (IV group) was controlled by intravenous patient-controlled analgesia (IV PCA). Postoperative pain in the second group (ES group) was controlled by epidural patient-controlled analgesia (E-PCA) or the remnant analgesic effects of spinal anesthesia. Plasma concentrations of N/OFQ were measured by enzyme-linked immunosorbent assay. Numerical rating scale (NRS) scores were recorded for all patients. Differences between the two groups with regards to plasma concentrations of N/OFQ and NRS scores were evaluated by the Mann-Whitney U-test. RESULTS: Plasma concentrations of N/OFQ (mean +/- SD) were 70.4 +/- 128.0 pg/ml in the IV group and 19.2 +/- 43.4 pg/ml in the ES group. NRS scores (mean +/- SD) were 3.1 +/- 1.9 in the IV group and 0.5 +/- 1.1 in the ES group. The differences in plasma N/OFQ concentrations between groups were not significant (P = 0.06). NRS scores were significantly lower in the ES group as compared with the IV group (P = 0.0019). CONCLUSIONS: Plasma concentrations of N/OFQ increase in acute postoperative pain states, but are not correlated with the level of postoperative pain. PMID- 24228147 TI - Synergistic anti-allodynic effect between intraperitoneal thalidomide and morphine on rat spinal nerve ligation-induced neuropathic pain. AB - BACKGROUND: Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats. METHODS: Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide. RESULTS: The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture. CONCLUSIONS: These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain. PMID- 24228148 TI - Unidirectional valve malfunction by the breakage or malposition of disc - two cases report -. AB - Malfunction of the unidirectional valve in a breathing circuit system may cause hypercapnia from the rebreathing of expired gas, ventilation failure, and barotrauma. Capnography is a useful method for monitoring the integrity of the unidirectional valve. We experienced two cases of malfunction of a unidirectional valve which caused leakage and reverse flow, diagnosed early as a change of the capnographic waveform. One case was caused by expiratory unidirectional valve breakage. The other was caused by an incorrectly-assembled inspiratory unidirectional valve. PMID- 24228149 TI - Acute onset Lance-Adams syndrome following brief exposure to severe hypoxia without cardiac arrest -a case report-. AB - Myoclonic status epilepticus (MSE) within the first 24 hours after cardiopulmonary resuscitation (CPR) predicts poor prognosis, enough to discontinue the treatment. In contrast, chronic MSE appearing a few days after CPR is called Lance-Adams syndrome (LAS), which is characterized by preserved intellect and a favorable prognosis. We herein report a case of LAS, which developed after a transient hypoxic event without an overt cardiac arrest due to hematoma formation in the neck after partial glossectomy. Differential diagnosis was also challenging as LAS was developed 8 hours after the hypoxic event. PMID- 24228150 TI - Coexistence of expanding abdominal aortic aneurysm and aggravated intervertebral disc extrusion -a case report-. AB - Abdominal aortic aneurysm is included in the differential diagnosis of lower back pain. Although rare, this important disease can cause potentially lethal complications. In this case, expanding abdominal aortic aneurysm coexisted with intervertebral disc extrusion. The diagnosis of abdominal aortic aneurysm was delayed, putting the patient at risk of aneurysmal rupture. In the management of patients with degenerative spinal diseases, we should not overlook the possibility of comorbidities such as an abdominal aortic aneurysm. We also suggest the importance of interpreting images more carefully, especially for elderly male patients. PMID- 24228151 TI - Coagulopathy following venous air embolism: a disastrous consequence -a case report-. AB - Venous air embolism (VAE) is a life-threatening complication of some surgical procedures. Though occurrence of VAE is frequent during neurosurgical procedures, coagulopathy following VAE has not previously been reported. Coagulation abnormalities are more commonly reported associated with fat or amniotic fluid embolism, but rarely with VAE. We present a case of massive VAE in sitting position leading to fatal coagulopathy even after successful resuscitation following the event. Coagulation abnormalities and bleeding can produce catastrophic consequences in neurosurgical patients. This report emphasizes the possibility of this potentially fatal complication in patients who have sustained a massive VAE. PMID- 24228152 TI - Anesthetic management of a patient with Lennox-Gastaut syndrome with intractable epilepsy -a case report-. AB - A 34-month-old female patient who had a prior history of generalized tonic-clonic seizures had been diagnosed with the Lennox-Gastuat syndrome. She was scheduled for epiblepharon repairs in both lower lids under general anesthesia. Preoperatively, her tonic seizure was poorly controlled with antiepileptic drugs. General anesthesia with thiopental and isoflurane was provided and the intraoperative course and the emergence of anesthesia were uneventful and smooth. PMID- 24228153 TI - Unilateral vocal cord paralysis following a short period of endotracheal intubation anesthesia. PMID- 24228154 TI - Difficult airway management in a case with lingual tonsil hypertrophy and temporo mandibular joint partial ankylosis. PMID- 24228155 TI - A failure of internal jugular vein catheterization caused by the internal jugular vein occlusion. PMID- 24228156 TI - The intermittent bolus infusions of rapid infusion system caused hypothermia during liver transplantation. PMID- 24228157 TI - Postoperative patient controlled analgesia in elderly Koreans: epidural versus intravenous administration. PMID- 24228158 TI - Lee fiberoptic intubating airway for facilitating orotracheal fiberoptic intubation. PMID- 24228160 TI - Therapeutic doses of clopidogrel increase fracture risk. PMID- 24228161 TI - Bone mass is regulated by a central IL-1-PSNS-bone axis. PMID- 24228159 TI - Role of mathematical modeling in bone fracture healing. AB - Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more recently by an anabolic/catabolic model. Data from humans and animal models have demonstrated crucial environmental conditions for optimal fracture healing, including the mechanical environment, blood supply and availability of mesenchymal stem cells. Fracture healing spans multiple length and time scales, making it difficult to know precisely which factors and/or phases to manipulate in order to obtain optimal fracture-repair outcomes. Deformations resulting from physiological loading or fracture fixation at the organ scale are sensed at the cellular scale by cells inside the fracture callus. These deformations together with autocrine and paracrine signals determine cellular differentiation, proliferation and migration. The local repair activities lead to new bone formation and stabilization of the fracture. Although experimental data are available at different spatial and temporal scales, it is not clear how these data can be linked to provide a holistic view of fracture healing. Mathematical modeling is a powerful tool to quantify conceptual models and to establish the missing links between experimental data obtained at different scales. The objective of this review is to introduce mathematical modeling to readers who are not familiar with this methodology and to demonstrate that once validated, such models can be used for hypothesis testing and to assist in clinical treatment as will be shown for the example of atrophic nonunions. PMID- 24228162 TI - The anabolic effect of PTH on bone is mediated by periostin. PMID- 24228163 TI - P2RY12 and its role in osteoclast activity and bone remodeling. PMID- 24228164 TI - Fracture risk prediction: importance of age, BMD and spine fracture status. AB - Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community dwelling men and women aged ?50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N=4725). Vertebral fractures were identified from lateral spine radiographs assessed using quantititative morphometry at baseline and end point. Nonvertebral fragility fractures were determined by questionnaire and confirmed using radiographs or medical records; fragility fracture was defined as occurring with minimal or no trauma. In this analysis, a model including age, BMD and spine fracture status provided a gradient of risk per s.d. (GR/s.d.) of 1.88 and captured most of the predictive information of a model including morphometric spine fracture status, BMD and all WHO clinical risk factors (GR/s.d. 1.92). For comparison, this model provided more information than a model considering BMD and the WHO clinical risk factors (GR/s.d. 1.74). These findings confirm the value of age, BMD and spine fracture status for predicting fracture risk. PMID- 24228165 TI - The endocannabinoid system, cannabinoids, and pain. AB - The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB 1 receptors) and in the periphery (primarily but not exclusively CB 2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Delta9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and beta-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain. PMID- 24228166 TI - Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain-At the Tipping Point? AB - The term "neuropathic pain" (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain's surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include "frameless stereotactic" neuronavigation systems, in which patients' head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials. PMID- 24228167 TI - Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile. AB - Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine. PMID- 24228168 TI - Neonatal pain in very preterm infants: long-term effects on brain, neurodevelopment and pain reactivity. AB - Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain related stress in the neonatal intensive care unit (NICU) in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24-32 weeks' gestational age). Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant's stress may be brain-protective. PMID- 24228170 TI - Pain Medicine in Crisis-A Possible Model toward a Solution: Empowering Community Medicine to Treat Chronic Pain. AB - Pain medicine in Israel and in the world has reached a crisis. The lack of available pain medicine services is resulting in the unsatisfactory treatment for chronic pain sufferers. The main causes of this crisis are: 1) the high prevalence of chronic pain, reaching levels of 17% in the adult population;2) the lack of appropriate training of primary care physicians in the field of chronic pain management; and 3) the paucity of consultation services in the field of chronic pain. In this journal article, we propose a possible model for the solution of the problem, based upon levels of treatment according to the severity of the disease and upon training of primary and secondary care physicians in the treatment of pain. According to the model, the vast majority of treatment and management will take place in the community after appropriate training of primary care physicians. More complex cases will be referred to secondary care community based pain clinics manned by physicians with further in-depth training. Only the most complex of patients, or those needing specialized treatment such as invasive analgesic therapy, will be referred to tertiary pain centers manned by specialists in pain medicine. Implementation of this model will necessitate training of primary care physicians and the establishment of secondary care facilities and can, in our opinion, pose a pragmatic solution for the hundreds of thousands of patients suffering from chronic pain. PMID- 24228169 TI - Completing the Pain Circuit: Recent Advances in Imaging Pain and Inflammation beyond the Central Nervous System. AB - This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain (peripheral or central), objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain. PMID- 24228171 TI - Impact of right-sided nephrectomy on long-term outcomes in retroperitoneoscopic live donor nephrectomy at single center. AB - Objective. To assess the long-term graft survival of right-sided retroperitoneoscopic live donor nephrectomy (RPLDN), we compared the outcomes of right- and left-sided RPLDN. Methods. Five hundred and thirty-three patients underwent live donor renal transplantation with allografts procured by RPLDN from July 2001 to August 2010 at our institute. Of these, 24 (4.5%) cases were selected for right-sided RPLDN (R-RPLDN) according to our criteria for donor kidney selection. Study variables included peri- and postoperative clinical data. Results. No significant differences were found in the recipients' postoperative graft function and incidence of slow graft function. Despite significant increased warm ischemic time (WIT: mean 5.9 min versus 4.7 min, P < 0.001) in R RPLDN compared to that in L-RPLDN, there was no significant difference between the two groups regarding long-term patient and graft survival. The complication rate in R-RPLDN was not significantly different compared to that in L-RPLDN (17% versus 6.5%, P = 0.132). No renal vein thrombosis was experienced in either groups. Conclusions. Although our study was retrospective and there was only a small number of R-RPLDN patients, R-RPLDN could be an option for laparoscopic live donor nephrectomy because of similar results, with the sole exception of WIT, in L-RPLDN, and its excellent long-term graft outcomes. PMID- 24228172 TI - Improved Method for the Detection and Quantification of Naegleria fowleri in Water and Sediment Using Immunomagnetic Separation and Real-Time PCR. AB - Primary amebic meningoencephalitis (PAM) is a rare and typically fatal infection caused by the thermophilic free-living ameba, Naegleria fowleri. In 2010, the first confirmed case of PAM acquired in Minnesota highlighted the need for improved detection and quantification methods in order to study the changing ecology of N. fowleri and to evaluate potential risk factors for increased exposure. An immunomagnetic separation (IMS) procedure and real-time PCR TaqMan assay were developed to recover and quantify N. fowleri in water and sediment samples. When one liter of lake water was seeded with N. fowleri strain CDC:V212, the method had an average recovery of 46% and detection limit of 14 amebas per liter of water. The method was then applied to sediment and water samples with unknown N. fowleri concentrations, resulting in positive direct detections by real-time PCR in 3 out of 16 samples and confirmation of N. fowleri culture in 6 of 16 samples. This study has resulted in a new method for detection and quantification of N. fowleri in water and sediment that should be a useful tool to facilitate studies of the physical, chemical, and biological factors associated with the presence and dynamics of N. fowleri in environmental systems. PMID- 24228173 TI - Direct Effect of Two Naphthalene-Sulfonyl-Indole Compounds on Toxoplasma gondii Tachyzoite. AB - Past studies have stated that the parasitostatic effect of IFN-gamma is most likely due to the starvation of Toxoplasma gondii for tryptophan in the host cell. The aim of this study was to evaluate the direct effect of two new Naphthalene-Sulfonyl-Indole compounds as competitive molecules for tryptophan on viability and infectivity of Toxoplasma tachyzoites. Tachyzoites of RH strain were incubated in various concentrations (25-800 MUM) of 1-(naphthalene-2 sulfonyl)-2,3-dihydro-1H-indole and 1-[5-(2,3-dihydro-1H-indole-1 sulfonyl)naphthalene-1-sulfonyl]-2,3-dihydro-1H-indole for 1.5 hours. Then, they were stained by PI and analyzed by FACS. To evaluate the infectivity, 2 * 10(6) tachyzoites exposed to the concentrations mentioned above were intraperitoneally inoculated into five mice from each group. Also, naive parasites and parasites exposed to DMSO (control) were inoculated in both groups of mice. The LD50 of 1 (naphthalene-2-sulfonyl)-2,3-dihydro-1H-indole was 62 MUmol whilst the quantity of 1-[5-(2,3-dihydro-1H-indole-1-sulfonyl)naphthalene-1-sulfonyl]-2,3-dihydro-1H indole was more than 800 MUmol. The infectivity of tachyzoites exposed to both of the compounds preserved and killed mice. No statistical correlation was seen between longevity of mice groups and different doses of the compounds. If we consider a well-organized transporter mechanism for indole compounds in the parasite, thus the designation of an antagonist that has indole groups can assist with the production of new drugs. PMID- 24228174 TI - Oxidative stress, vascular remodeling, and vascular inflammation in hypertension. PMID- 24228175 TI - Assessing Systems of Care for US Children with Epilepsy/Seizure Disorder. AB - Background. The proportion of US children with special health care needs (CSHCN) with epilepsy/seizure disorder who receive care in high-quality health service systems was examined. Methodology. We analyzed data for 40,242 CSHCN from the 2009-2010 National Survey of CSHCN and compared CSHCN with epilepsy/seizure disorder to CSHCN without epilepsy/seizure disorder. Measures included attainment rates for 6 federal quality indicators with comparisons conducted using chi square and logistic regression methods. In addition, CSHCN with epilepsy/seizure disorder were compared to CSHCN without epilepsy/seizure disorder on the basis of 14 unmet health care needs. Results. Lower attainment rates for receiving comprehensive care in a medical home and easily accessible community-based services were found for CSHCN with epilepsy/seizure disorder versus CSHCN without epilepsy/seizure disorder (medical home: 32% versus 43%; accessible community based services: 50% versus 66%, resp.) in unadjusted analyses. Lower adjusted odds for these indicators as well as greater unmet need for specialists, dentistry, prescriptions, therapies, and mental health care were also found for CSHCN with epilepsy/seizure disorder. Conclusions. Further efforts are needed to improve attainment of high-quality health care services for CSHCN with epilepsy/seizure disorders. PMID- 24228176 TI - The role for epigenetic modifications in pain and analgesia response. AB - Pain remains a poorly understood and managed symptom. A limited mechanistic understanding of interindividual differences in pain and analgesia response shapes current approaches to assessment and treatment. Opportunities exist to improve pain care through increased understanding of how dynamic epigenomic remodeling shapes injury, illness, pain, and treatment response. Tightly regulated alterations of the DNA-histone chromatin complex enable cells to control transcription, replication, gene expression, and protein production. Pathological alterations to chromatin shape the ability of the cell to respond to physiologic and environmental cues leading to disease and reduced treatment effectiveness. This review provides an overview of critical epigenetic processes shaping pathology and pain, highlights current research support for the role of epigenomic modification in the development of chronic pain, and summarizes the therapeutic potential to alter epigenetic processes to improve health outcomes. PMID- 24228178 TI - Motorcycle Related Injuries among Rural Dwellers in Irrua, Nigeria: Characteristics and Correlates. AB - Background. The escalating use of motorcycle for commercial transportation of commuters and goods has resulted in an increase in morbidity and mortality from road traffic injuries. Objectives. To study the characteristics of motorcycle injuries seen in Irrua, Nigeria. Materials and Methods. This is a one-year prospective study of all patients seen from January 1, 2009, to December 31, 2009. A structured proforma was filled for all consecutive crash victims involving a motorcycle. Results. Motorcycle injuries accounted for 11.6% of attendance in surgical emergency room (142 out of 1,214); 76.8% were males. Amongst victims 47.1% were riders, 42.9%, passengers, and 7.8% pedestrians. Extremity injury accounted for 42.2% while head injury occurred in 21.8%. There were 9 deaths (6.3%). In this study no victim used crash helmet. Conclusion. Banning of motorcycle for commercial use and the introduction of tricycles into rural/suburban comminutes may be an important preventive strategy. PMID- 24228177 TI - Current controversies in the prediction, diagnosis, and management of cerebral vasospasm: where do we stand? AB - Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 persons in the United States each year. Around 30 percent of patients with aneurysmal subarachnoid hemorrhage suffer from cerebral ischemia and infarction due to cerebral vasospasm, a leading cause of treatable death and disability following aneurysmal subarachnoid hemorrhage. Methods used to predict, diagnose, and manage vasospasm are the topic of recent active research. This paper utilizes a comprehensive review of the recent literature to address controversies surrounding these topics. Evidence regarding the effect of age, smoking, and cocaine use on the incidence and outcome of vasospasm is reviewed. The abilities of different computed tomography grading schemes to predict vasospasm in the aftermath of subarachnoid hemorrhage are presented. Additionally, the utility of different diagnostic methods for the detection and visualization of vasospasm, including transcranial Doppler ultrasonography, CT angiography, digital subtraction angiography, and CT perfusion imaging is discussed. Finally, the recent literature regarding interventions for the prophylaxis and treatment of vasospasm, including hyperdynamic therapy, albumin, calcium channel agonists, statins, magnesium sulfate, and endothelin antagonists is summarized. Recent studies regarding each topic were reviewed for consensus recommendations from the literature, which were then presented. PMID- 24228180 TI - Elbow dislocations: a review ranging from soft tissue injuries to complex elbow fracture dislocations. AB - This review on elbow dislocations describes ligament and bone injuries as well as the typical injury mechanisms and the main classifications of elbow dislocations. Current treatment concepts of simple, that is, stable, or complex unstable elbow dislocations are outlined by means of case reports. Special emphasis is put on injuries to the medial ulnar collateral ligament (MUCL) and on posttraumatic elbow stiffness. PMID- 24228181 TI - The SomnuSeal Oral Mask Is Reasonably Tolerated by Otherwise CPAP Noncompliant Patients with OSA. AB - Compliance with CPAP is the major limiting factor in treating patients with OSA. The novel SomnuSeal mask is an oral self-adaptable mask located between the teeth and the lips ensuring that there are no air leaks or skin abrasions. Fifty patients with AHI > 20, who failed previous CPAP trials, were asked to sleep with the mask for one month. In all patients, the mask was connected to an AutoPAP machine with a heated humidifier. Efficacy, convenience, and compliance (average usage for 4 or more hours per night) were monitored. Fifty patients (41 m and 9 f, mean age 57 +/- 12 years, BMI 33.6 +/- 4.9 kg/m(2), and AHI 47 +/- 23/h) participated. Eleven were classified as compliant (average mask usage of 26 nights, 4.7 hours per night), five were only partially compliant (average usage of 13 nights, 2.9 hours per night), and 34 could not comply with it. In all patients who slept with it, the efficacy (assessed by residual AHI derived from the CPAP device) was good with an AHI of less than 8/hour. Interestingly, the required optimal pressure decreased from an average of 9.3 cmH2O to 4.6 cmH2O. The SomnuSeal oral interface is effective and may result in converting noncompliant untreated patients with OSA into well-treated ones. PMID- 24228179 TI - Targeting antigens to dendritic cell receptors for vaccine development. AB - Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed. PMID- 24228183 TI - Breast Mass and Lytic Bone Lesions: A Rare Presentation of Non-Hodgkin's Lymphoma Arising in the Breast. AB - Background. Primary breast lymphoma is a rare malignancy representing less than 1% of all tumors presenting in the breast. Case Presentation. A 55-year-old woman presented with altered mental status due to severe hypercalcemia and was found to have a large breast mass with lytic bone lesions in the calvarium of the skull. Biopsy of the mass revealed diffuse large B-cell lymphoma. Staging workup did not reveal any visceral organ or distant lymph node involvement. The patient's bone marrow biopsy was positive for involvement with lymphoma. Interestingly, the patient also had a non quantifiable IgA kappa monoclonal protein in the serum. Conclusion. Here, we describe a common presentation in medical oncology, that is, a patient presenting as a clinically advanced breast tumor with hypercalcemia from lytic bone lesions. However, diagnostic workup led to the diagnosis of another common malignancy in an uncommon location, namely, diffuse large B-cell lymphoma arising in the breast. PMID- 24228182 TI - Insulin deprivation decreases caspase-dependent apoptotic signaling in cultured rat sertoli cells. AB - Insulin is essential for the regulation of glucose homeostasis. Insulin dysfunction occurs in several pathologies, such as diabetes mellitus, which is associated with fertility problems. Somatic Sertoli cells (SCs) not only metabolize glucose to lactate, which is the central energy source used by developing germ cells, but also determine the germ cell population size. If a deregulation in SCs apoptosis occurs, it will affect germ cells, compromising spermatogenesis. As SCs apoptotic signaling is a hormonally regulated process, we hypothesized that the lack of insulin could lead to alterations in apoptotic signaling. Therefore, we examined the effect of insulin deprivation on several markers of apoptotic signaling in cultured rat SCs. We determined mRNA and protein expression of apoptotic markers as well as caspase-3 activity. SCs cultured in insulin deprivation demonstrated a significant decrease on mRNA levels of p53, Bax, caspase-9, and caspase-3 followed by a significant increase of Bax and decrease of caspase-9 protein levels relatively to the control. Caspase-3 activity was also decreased in SCs cultured in insulin deprivation conditions. Our results show that insulin deprivation decreases caspase-dependent apoptotic signaling in cultured rat SCs evidencing a possible mechanism by which lack of insulin can affect spermatogenesis and fertility. PMID- 24228184 TI - Sarcomatoid carcinoma of male urethra with bone and lung metastases presenting as urethral stricture. AB - A 57-year-old man who presented with urinary retention was found to have a sarcomatoid carcinoma of the urethra. Evaluation with CT scan of the abdomen and pelvis revealed multiple pulmonary nodules and osteolytic lesions of left posterior ribs. After external beam radiation therapy and six cycles of systemic chemotherapy, patient underwent a surgical resection of the urethral cancer. After his surgery, patient was also found to have multiple brain metastases and underwent whole brain radiation therapy, nine months after his initial diagnosis. Sarcomatoid carcinomas of the genitourinary tract are extremely rare tumors that require a very aggressive, multimodal treatment approach. PMID- 24228185 TI - Cardiovascular risk and hippocampal thickness in Alzheimer's disease. AB - Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease. PMID- 24228186 TI - Decreased copper in Alzheimer's disease brain is predominantly in the soluble extractable fraction. AB - Alzheimer's disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble (P < 0.05) and total homogenate (P < 0.05) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD. PMID- 24228187 TI - Prospective single-site experience with radiofrequency-targeted vertebral augmentation for osteoporotic vertebral compression fracture. AB - Vertebral augmentation procedures are widely used to treat osteoporotic vertebral compression fractures (VCFs). We report our initial experience with radiofrequency-targeted vertebral augmentation (RF-TVA) in 20 patients aged 50 to 90 years with single-level, symptomatic osteoporotic VCF between T10 and L5, back pain severity > 4 on a 0 to 10 scale, Oswestry Disability Index >= 21%, 20% to 90% vertebral height loss compared to adjacent vertebral body, and fracture age < 6 months. After treatment, patients were followed through hospital discharge and returned for visits after 1 week, 1 month, and 3 months. Back pain severity improved 66% (P < 0.001), from 7.9 (95% CI: 7.1 to 8.6) at pretreatment to 2.7 (95% CI: 1.5 to 4.0) at 3 months. Back function improved 46% (P < 0.001), from 74 (95% CI: 69% to 79%) at pretreatment to 40 (95% CI: 33% to 47%) at 3 months. The percentage of patients regularly consuming pain medication was 70% at pretreatment and only 21% at 3 months. No adverse events related to the device or procedure were reported. RF-TVA reduces back pain severity, improves back function, and reduces pain medication requirements with no observed complications in patients with osteoporotic VCF. PMID- 24228188 TI - UPLC-TOF-MS Characterization and Identification of Bioactive Iridoids in Cornus mas Fruit. AB - Cornus mas L. is indigenous to Europe and parts of Asia. Although Cornus is widely considered to be an iridoid rich genera, only two iridoids have been previously found in this plant. The lack of information on taxonomically and biologically active iridoids prompted us to develop and optimize an analytical method for characterization of additional phytochemicals in C. mas fruit. An ultra performance liquid chromatography (UPLC) coupled with photodiode array spectrophotometry (PDA) and electrospray time-of-flight mass spectrometry (ESI TOF-MS) was employed and mass parameters were optimized. Identification was made by elucidating the mass spectral data and further confirmed by comparing retention times and UV spectra of target peaks with those of reference compounds. Primary DNA damage and antigenotoxicity tests in E. coli PQ37 were used to screen the iridoids for biological activity. As a result, ten phytochemicals were identified, including iridoids loganic acid, loganin, sweroside, and cornuside. Nine of these were reported for the first time from C. mas fruit. The iridoids did not induce SOS repair of DNA, indicating a lack of genotoxic activity in E. coli PQ37. However, loganin, sweroside, and cornuside did reduce the amount of DNA damage caused by 4-nitroquinoline 1-oxide, suggesting potential antigenotoxic activity. PMID- 24228189 TI - Resistant starch: promise for improving human health. AB - Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized. PMID- 24228190 TI - Iron biology, immunology, aging, and obesity: four fields connected by the small peptide hormone hepcidin. AB - Iron status and immune response become impaired in situations that involve chronic inflammation, such as obesity or aging. Little is known, however, about the additional burden that obesity may place on the iron status and immune response in the elderly. This question is relevant given the rising numbers of elderly obese (BMI >30 kg/m(2)) individuals and the high prevalence of iron deficiency worldwide. Iron is necessary for proper function of both the innate and adaptive immune system. Hepcidin, a peptide hormone that regulates cellular iron export, is essential for the maintenance of iron homeostasis. Therefore, since immune cells require iron for proper function hepcidin may also play an important role in immune response. In this review, we summarize the evidence for hepcidin as a link between the fields of gerontology, obesity, iron biology, and immunology. We also identify several gaps in knowledge and unanswered questions pertaining to iron homeostasis and immunity in obese populations. Finally, we review studies that have shown the impact of weight loss, focusing on calorie restriction, iron homeostasis, and immunity. These studies are important both in elucidating mechanistic links between obesity and health impairments and identifying possible approaches to target immune impairment and iron deficiency as comorbidities of obesity. PMID- 24228191 TI - Cranberries and their bioactive constituents in human health. AB - Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present in most other fruit. Basic research has suggested a number of potential mechanisms of action of cranberry bioactives, although further molecular studies are necessary. Human studies on the health effects of cranberry products have focused principally on urinary tract and cardiovascular health, with some attention also directed to oral health and gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the recurrence of urinary tract infections is important because a nutritional approach to this condition could lower the use of antibiotic treatment and the consequent development of resistance to these drugs. There is encouraging, but limited, evidence of a cardioprotective effect of cranberries mediated via actions on antioxidant capacity and lipoprotein profiles. The mixed outcomes from clinical studies with cranberry products could result from interventions testing a variety of products, often uncharacterized in their composition of bioactives, using different doses and regimens, as well as the absence of a biomarker for compliance to the protocol. Daily consumption of a variety of fruit is necessary to achieve a healthy dietary pattern, meet recommendations for micronutrient intake, and promote the intake of a diversity of phytochemicals. Berry fruit, including cranberries, represent a rich source of phenolic bioactives that may contribute to human health. PMID- 24228192 TI - The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol. AB - Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, >=10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when beta-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c. PMID- 24228193 TI - Recent developments in multivitamin/mineral research. AB - The 2010 Dietary Guidelines Advisory Committee was charged with the task of investigating the effects of multivitamin/mineral supplements on healthy populations and also on those with chronic disease. The evidence from which the committee prepared its conclusions was graded on 5 fundamental criteria: quality, consistency, quantity, clinical impact, and generalizability. The committee concluded that for the general healthy population, evidence was insufficient to make a multivitamin/mineral recommendation. On the other hand, the committee noted the value of some supplemental nutrients for at-risk populations such as iron, folic acid, and vitamin B-12. However, most of the studies referenced for the research used the conventional, all-encompassing, and oversimplified definition of a multivitamin/mineral as being a supplement containing 3 or more vitamins with or without minerals. In the few years since the committee released its 2010 report, several randomized clinical trials showing the benefits of daily multivitamin/mineral supplementation have been completed using supplements containing at least 10 or more vitamins and/or minerals, but there also continues to be some reports that do not find benefit from such supplements. Furthermore, several steps have been taken to advance the science behind these supplements so that consumers, physicians, and government agencies can all have more confidence in understanding the role of supplemental nutrition in the American diet. This review provides new evidence from 2010 onward addressing the committee's primary concerns about multivitamin/mineral research in regard to improving public health. It also includes several recent studies that may be of interest to future committees indicating the potential benefits of these supplements on improving the cognitive performance and mental well-being of healthy populations. PMID- 24228195 TI - State Indicator Report on Fruits and Vegetables, 2013, Centers for Disease Control and Prevention, Atlanta, GA. PMID- 24228196 TI - Navigating the current job market--grab hold of your future now! AB - Although the U.S. federal government, the National Science Foundation, and other influential groups have called for American universities to educate and train more scientists, a recent article in the Washington Post and broadcasting on National Public Radio affirmed a harsh reality: there are too few jobs for today's young scientists. Essentially, landing a job in science doesn't just happen, you must prepare! The intent of this education track session, targeted to students, postdoctorates, junior faculty, and other early- to midcareer professionals was to provide insights on trends in the current job market and offer strategies and resources to be competitive. The session featured speakers representing different work environments, such as academia, industry, health care institutions, public relations, and entrepreneurial positions. PMID- 24228197 TI - Health, nutrition, and cost outcomes of human milk feedings for very low birthweight infants. AB - This symposium examined the impact of human milk (HM) from the infant's own mother on health, nutrition, and cost outcomes in very low birthweight (VLBW; <1500 g birthweight) infants. The 4 symposium speakers presented original research and summarized existing evidence about these primary outcomes. The conclusions from the symposium suggest that: 1) HM feedings for VLBW infants in the neonatal intensive care unit (NICU) reduce the risks and the associated costs of late onset sepsis and necrotizing enterocolitis (NEC); 2) the gut microbiota of the VLBW infant is influenced by multiple factors, some of which are modifiable, and that the milk microbiota affects the developing gut microbiota in a positive manner; 3) the clinical realties of feeding HM in the NICU that compromise safety and efficacy of HM can be addressed with evidence-based clinical practices; and 4) piglets can serve as a model for the premature infant to assess the impact of HM and formula additives on intestinal development. PMID- 24228194 TI - Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis. AB - Mitochondrial biogenesis is a critical metabolic adaptation to aerobic exercise training that results in enhanced mitochondrial size, content, number, and activity. Recent evidence has shown that dietary manipulation can further enhance mitochondrial adaptations to aerobic exercise training, which may delay skeletal muscle fatigue and enhance exercise performance. Specifically, studies have demonstrated that combining carbohydrate restriction (endogenous and exogenous) with a single bout of aerobic exercise potentiates the beneficial effects of exercise on markers of mitochondrial biogenesis. Additionally, studies have demonstrated that high-quality protein supplementation enhances anabolic skeletal muscle intracellular signaling and mitochondrial protein synthesis following a single bout of aerobic exercise. Mitochondrial biogenesis is stimulated by complex intracellular signaling pathways that appear to be primarily regulated by 5'AMP-activated protein kinase and p38 mitogen-activated protein kinase mediated through proliferator-activated gamma receptor co-activator 1 alpha activation, resulting in increased mitochondrial DNA expression and enhanced skeletal muscle oxidative capacity. However, the mechanisms by which concomitant carbohydrate restriction and dietary protein supplementation modulates mitochondrial adaptations to aerobic exercise training remains unclear. This review summarizes intracellular regulation of mitochondrial biogenesis and the effects of carbohydrate restriction and protein supplementation on mitochondrial adaptations to aerobic exercise. PMID- 24228198 TI - omega-3 fatty acids in the prevention of cognitive decline in humans. AB - The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (omega-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eepsilon4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-beta deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA. PMID- 24228199 TI - The metabolic and endocrine response and health implications of consuming sugar sweetened beverages: findings from recent randomized controlled trials. AB - Fructose-containing sugars, including fructose itself, high fructose corn syrup (HFCS), and sucrose have engendered considerable controversy. The effects of HFCS and sucrose in sugar-sweetened beverages, in particular, have generated intense scientific debate that has spilled over to the public. This controversy is related to well-known differences in metabolism between fructose and glucose in the liver. In addition, research studies have often been conducted comparing pure fructose and pure glucose even though neither is consumed to any appreciable degree in isolation in the human diet. Other evidence has been drawn from animal studies and epidemiologic or cohort studies. Few randomized controlled trials (RCTs) have compared HFCS with sucrose (the 2 sugars most commonly consumed in the human diet) at dosage amounts within the normal human consumption range. This review compares results of recently concluded RCTs with other forms of evidence related to fructose, HFCS, and sucrose. We conclude that great caution must be used when suggesting adverse health effects of consuming these sugars in the normal way they are consumed and at the normal amounts in the human diet, because RCTs do not support adverse health consequences at these doses when employing these sugars. PMID- 24228200 TI - From efficacy research to large-scale impact on undernutrition: the role of organizational cultures. AB - Undernutrition in low-income countries is receiving unprecedented attention at global and national levels due to the convergence of many forces, including strong evidence concerning its magnitude, consequences, and potential solutions and effective advocacy by many organizations. The translation of this attention into large-scale reductions in undernutrition at the country level requires the alignment and support of many organizations in the development and implementation of a coherent policy agenda for nutrition, including the strengthening of operational and strategic capacities and a supportive research agenda. However, many countries experience difficulties achieving such alignment. This article uses the concept of organizational culture to better understand some of the reasons for these difficulties. This concept is applied to the constellation of organizations that make up the "National Nutrition Network" in a given country and some of the individual organizations within that network, including academic institutions that conduct research on undernutrition. We illustrate this concept through a case study involving a middle-income country. We conclude that efforts to align organizations in support of coherent nutrition agendas should do the following: 1) make intentional and sustained efforts to foster common understanding, shared learning, and socialization of new members and other elements of a shared culture among partners; 2) seek a way to frame problems and solutions in a fashion that enables individual organizations to secure some of their particular interests by joining the effort; and 3) not only advocate on the importance of nutrition but also insist that high-level officials hold organizations accountable for aligning in support of common-interest solutions (through some elements of a common culture) that can be effective and appropriate in the national context. We further conclude that a culture change is needed within academic departments if the discipline of nutrition is to play a central role in translating the findings from efficacy trials into large-scale reductions in undernutrition. PMID- 24228203 TI - Evidence needed to inform the next dietary reference intakes for iodine. AB - In 2001, Dietary Reference Intakes (DRIs) for iodine were set for the different gender and life-stage groups by the Institute of Medicine. Because of the serious consequences of iodine deficiency for the developing fetus and infant, there is particular interest in further understanding optimal iodine nutrition and improving the monitoring of iodine status, particularly during infancy, pregnancy, and lactation. This review discusses the basis for the current DRIs for iodine and the evidence that may be needed for considering and conducting the reevaluation of one or more of the DRIs. PMID- 24228202 TI - Treatment of parenteral nutrition-associated liver disease: the role of lipid emulsions. AB - Parenteral nutrition is a life-saving therapy for infants with intestinal failure. However, long-term parenteral nutrition carries the risk of progressive liver disease. Substantial data has implicated components of parenteral soybean oil in the pathogenesis of parenteral nutrition-associated liver disease (PNALD). Elevated serum concentrations of phytosterols, an abundance of omega-6 polyunsaturated fatty acids, and a relative paucity of alpha-tocopherol have been associated with the risk of cholestasis and hepatic injury observed in PNALD. Currently available treatment strategies include the reduction of the dose of administered parenteral soybean oil and/or the replacement of parenteral soybean oil with alternative parenteral lipid emulsions. The purpose of this review is to provide an overview of the pathogenetic mechanisms associated with the development of PNALD and the data evaluating currently available treatment strategies. PMID- 24228201 TI - Hepatic fatty acid trafficking: multiple forks in the road. AB - The liver plays a unique, central role in regulating lipid metabolism. In addition to influencing hepatic function and disease, changes in specific pathways of fatty acid (FA) metabolism have wide-ranging effects on the metabolism of other nutrients, extra-hepatic physiology, and the development of metabolic diseases. The high prevalence of nonalcoholic fatty liver disease (NAFLD) has led to increased efforts to characterize the underlying biology of hepatic energy metabolism and FA trafficking that leads to disease development. Recent advances have uncovered novel roles of metabolic pathways and specific enzymes in generating lipids important for cellular processes such as signal transduction and transcriptional activation. These studies have also advanced our understanding of key branch points involving FA partitioning between metabolic pathways and have identified new roles for lipid droplets in these events. This review covers recent advances in our understanding of FA trafficking and its regulation. An emphasis will be placed on branch points in these pathways and how alterations in FA trafficking contribute to NAFLD and related comorbidities. PMID- 24228205 TI - Prevalence and Degree of Breast Arterial Calcifications on Mammography: A Cross sectional Analysis. AB - OBJECTIVES: The purpose of this study is to establish a database including prevalence and degree of breast arterial calcifications (BAC) in our population of women presenting for mammography. MATERIALS AND METHODS: The mammograms of 1786 women over the age of 40 years were examined for the presence and degree of BAC. Statistical analysis was performed to correlate patient's age and ethnic origin with the presence and degree of BAC. RESULTS: There was statistically significant and strong correlation between the patient's age and presence of BAC. There was also a less strong yet statistically significant correlation between patient age and degree of BAC. Regression analysis showed the likelihood of BAC at various ages. The prevalence of BAC is only 2% of women under 50 years of age; the prevalence of Grade 2-3 BAC is only 1% in women under 60 years of age. CONCLUSION: There is a predictable increase with age in both prevalence and degree of BAC in women. The presence of high degree BAC in women under 60 years of age or any BAC in women under 50 years of age is unusual. PMID- 24228204 TI - The connection between dietary phosphorus, cardiovascular disease, and mortality: where we stand and what we need to know. AB - Disorders of phosphorus metabolism are independent risk factors for cardiovascular disease. Because excess dietary phosphorus intake is common in the general population and plays a central role in disturbances in phosphorus homeostasis, these findings have fueled interest in restricting phosphorus intake as a potential therapy for improving cardiovascular outcomes. Although experimental and observational data support this possibility, current limitations in the assessment of dietary phosphorus consumption in free-living populations and the lack of reliable biomarkers of the effects of dietary phosphorus on cardiovascular health pose major barriers to the design and conduct of trials assessing the efficacy of phosphorus restriction in improving cardiovascular health. Fibroblast growth factor 23 and Klotho are novel mediators of phosphorus metabolism that are tightly linked to dietary phosphorus intake and show promise as integrated biomarkers of phosphorus excess and its long-term health consequences. Advances in the understanding of how these hormones are associated with diet and phosphorus metabolism will likely bolster future efforts to assess the true health consequences of excess phosphorus intake and whether restricting phosphorus intake has salutary effects on cardiovascular health. PMID- 24228206 TI - Isolated tuberculous tenosynovitis of the anterior tibial and extensor digitorum longus tendons. AB - Musculoskeletal system is involved in 1-5% of extrapulmonary cases of tuberculosis. Tuberculous tenosynovitis is a rare form of musculoskeletal tuberculosis. Tuberculosis of the tendon sheath in the hand has been seen in a few cases. Involvement of the tendons of the leg is less common. Diagnosis is not easy as there are no specific clinical symptoms or signs. A 33-year-old male presented with painful swelling in the distal right lower limb that caused restriction of movement. Imaging studies showed inflammation and infection of the extensor digitorium longus and tibialis anterior tendons. Histopathological studies showed a necrotizing granulomatous inflammation in the synovial tissue. A diagnosis of tuberculosis was made and medical treatment was initiated that proved successful. Patient remained infection-free at 26-month follow-up examination. PMID- 24228207 TI - Acquired arteriovenous fistula of the breast following ultrasound guided biopsy of invasive ductal carcinoma. AB - Image guided large-core breast biopsies are commonly performed procedures with relatively rare complications. The majority of these complications are minor, though at times more significant vascular injuries can occur with these biopsies as demonstrated by this case. Patient developed a pulsatile vascular breast mass after an ultrasound guided breast biopsy of invasive ductal carcinoma. Sonographic evaluation of this new breast mass demonstrated this mass to represent an arteriovenous fistula (AVF). Though multiple therapies are available for an iatrogenic fistula within the breast, the AVF was surgically excised in this case as it was immediately adjacent to a known cancer. PMID- 24228208 TI - Adenoid cystic carcinoma of the upper trachea: a rare neoplasm. AB - Primary malignant tracheal tumors are not common and adenoid cystic carcinoma (ACC) of trachea is rare. We report an extremely rare case of ACC of proximal trachea, which was diagnosed in a 42-year-old male who presents with 6-month history of dyspnea. Lateral skiagram of neck, computed tomography, and magnetic resonance imaging revealed a broad-based polypoidal soft tissue mass arising from posterior wall of the proximal trachea. Biopsy confirmed the diagnosis of ACC. The patient was treated by surgical resection followed by radiotherapy and is on regular follow-up. Follow-up at 18 months post-treatment showed no local recurrence or distant metastases. The literature on tracheal ACC is reviewed. Image findings are briefly discussed. PMID- 24228209 TI - Nasal lobular capillary hemangioma. AB - Nasal lobular capillary hemangioma is a rare benign tumor of the paranasal sinuses. This lesion is believed to grow rapidly in size over time. The exact etiopathogenesis is still a dilemma. We discuss a case of nasal lobular capillary hemangioma presenting with a history of epistaxis. Contrast enhanced computed tomography of paranasal sinuses revealed an intensely enhancing soft-tissue mass in the left nasal cavity and left middle and inferior meati with no obvious bony remodeling or destruction. We present imaging and pathologic features of nasal lobular capillary hemangioma and differentiate it from other entities like nasal angiofibroma. PMID- 24228210 TI - Multispectral Photoacoustic Imaging of Prostate Cancer: Preliminary Ex-vivo Results. AB - OBJECTIVE: The objective of this study is to validate if ex-vivo multispectral photoacoustic (PA) imaging can differentiate between malignant prostate tissue, benign prostatic hyperplasia (BPH), and normal human prostate tissue. MATERIALS AND METHODS: Institutional Review Board's approval was obtained for this study. A total of 30 patients undergoing prostatectomy for biopsy-confirmed prostate cancer were included in this study with informed consent. Multispectral PA imaging was performed on surgically excised prostate tissue and chromophore images that represent optical absorption of deoxyhemoglobin (dHb), oxyhemoglobin (HbO2), lipid, and water were reconstructed. After the imaging procedure is completed, malignant prostate, BPH and normal prostate regions were marked by the genitourinary pathologist on histopathology slides and digital images of marked histopathology slides were obtained. The histopathology images were co-registered with chromophore images. Region of interest (ROI) corresponding to malignant prostate, BPH and normal prostate were defined on the chromophore images. Pixel values within each ROI were then averaged to determine mean intensities of dHb, HbO2, lipid, and water. RESULTS: Our preliminary results show that there is statistically significant difference in mean intensity of dHb (P < 0.0001) and lipid (P = 0.0251) between malignant prostate and normal prostate tissue. There was difference in mean intensity of dHb (P < 0.0001) between malignant prostate and BPH. Sensitivity, specificity, positive predictive value, and negative predictive value of our imaging system were found to be 81.3%, 96.2%, 92.9% and 89.3% respectively. CONCLUSION: Our preliminary results of ex-vivo human prostate study suggest that multispectral PA imaging can differentiate between malignant prostate, BPH and normal prostate tissue. PMID- 24228211 TI - Benign medullary fibroma of the kidney: a rare diagnostic dilemma. AB - Renomedullary interstitial cell tumor or medullary fibroma, is a small tumor that commonly presents as an incidental finding, but in rare cases maybe large and symptomatic. Although it is a benign tumor, it is difficult to differentiate this lesion from other malignancies of the kidney on radiological basis and hence many patients undergo radical nephrectomy. We present a case of renal medullary fibroma and various nuances associated with radiological identification of this lesion and its management related dilemmas. PMID- 24228212 TI - Lymphangioma circumscriptum in an adult: an unusual oral presentation. AB - Lymphangioma is a benign hamartomatous tumor of lymphatic vessels. This lymphatic malformation is characterized by an abnormal proliferation of lymphatic vessels. Extra-oral lymphangiomas occur more frequently in the neck region predominantly in the posterior triangle, while intra-oral lymphangiomas are commonly seen in the tongue mainly on the dorsum surface. Various imaging modalities such as ultrasound and color Doppler are very useful in viewing the extent of the lesion. In most of the cases, surgical excision is the treatment of choice. The prognosis is good for most patients, but recurrence has also been reported in some cases, presumably because the lesion is interwoven between muscle fibers, preventing complete removal. This case report discusses the clinical features, color Doppler imaging, histopathology, and treatment of lymphangioma. PMID- 24228213 TI - Giant choledochal cyst mimicking massive gallbladder hydrops in an adult patient: multi detector computed tomography and magnetic resonance imaging findings correlated to gross and histopathological findings. AB - Choledochal cysts are uncommon congenital anomalies of the biliary tree, commonly presenting in infancy, generally in the 1(st) year of life. Presentation in adult life is less common, accounting for 20% of cases. A 19-year-old female patient presented to the Emergency Department with severe abdominal distension, a palpable abdominal mass, mild jaundice and low grade fever. Ultrasound, computed tomography (CT) and magnetic resonance imaging of the abdomen showed a massive septated cystic lesion filling the entire abdomen with a significant mass effect on surrounding structures. Origin of the lesion was unclear and diagnosis included a giant mesenteric or duplication cyst, massive gallbladder with hydrops, biliary cystadenoma and giant choledochal cyst, among others. Final diagnosis was a Type IA choledochal cyst with massive asymmetric cystic dilatation of the extra-hepatic segments of the left hepatic duct with asymmetric dilatation of the right hepatic duct. Patient had an uneventful recovery after resection of the entire extrahepatic cyst and Roux-en-Y hepaticojejunostomy at the level of the hilum. In this article, we correlate CT and MRI findings to gross and histopathological findings of this giant Todani's Type IA choledochal cyst. PMID- 24228214 TI - Radiographically Occult Latent Radiogenic Osteosarcoma Uncovered on Tc-99m Methylene-diphosphonate Bone Scintigraphy. AB - We present a case of a 70-year-old male who was referred for a technetium-99m methylene-diphosphonate bone scan for mild left hip pain and an elevated alkaline phosphatase level of 770 units/L. No additional information was provided and the patient's history was limited due to a language barrier. We were able to ascertain that the patient had a remote history of prostate cancer, which had been treated with radiation. Originally, we felt the bone scan was compatible with Paget's disease; however, further work-up revealed the presence of osteosarcoma, which was potentially radiation-induced. PMID- 24228215 TI - Truncus arteriosus with persistent left superior vena cava: cardiac computed tomography findings in an unrepaired adult patient. AB - Truncus arteriosus (TA), a rare complex congenital cardiac disease in which systemic pulmonary and coronary circulations originate from a common vessel, develops due to failure of separation of the common trunk during embryonic life. In this case report, we discuss a 24-year-old patient with TA in whom a computed tomography angiography was performed. To the best of our knowledge, no case has been reported so far where an adult had combined left superior vena cava and pulmonary vein anomaly. PMID- 24228216 TI - Concepts for Liver Segment Classification: Neither Old Ones nor New Ones, but a Comprehensive One. AB - Concepts dealing with the subdivision of the human liver into independent vascular and biliary territories are applied routinely in radiological, surgical, and gastroenterological practice. Despite Couinaud's widely used eight-segments scheme, opinions on the issue differ considerably between authors. The aim of this article is to illustrate the scientific basis for understanding and harmonizing inconsistencies between seemingly contradictory observations. Possible clinical implications are addressed. PMID- 24228217 TI - Superior gluteal artery pseudoaneurysm presenting as a gluteal mass: case report and review of literature. AB - Aneurysms of the gluteal arteries are very rare with the majority being post trauma pseudoaneurysms. Generally, management of these aneurysms could be surgical or through endovascular techniques. We present a case of a superior gluteal artery pseudoaneurysm complicating a pelvic fracture that presented as a gluteal mass. It was successfully treated by transcatheter coil embolization. We review the presentation, imaging, and treatment options. Aneurysms have to be considered in the differential diagnosis of soft tissue masses, therefore lesion intervention by aspiration or needle biopsy should not be tried before ruling out a possible vascular nature which will easily be revealed by ultrasound Doppler or computed tomography scans. PMID- 24228219 TI - Novel group of podovirus infecting the marine bacterium Alteromonas macleodii. AB - Four novel, closely related podoviruses, which displayed lytic activity against the gamma-proteobacterium Alteromonas macleodii, have been isolated and sequenced. Alterophages AltAD45-P1 to P4 were obtained from water recovered near a fish farm in the Mediterranean Sea. Their morphology indicates that they belong to the Podoviridae. Their linear and dsDNA genomes are 100-104 kb in size, remarkably larger than any other described podovirus. The four AltAD45-phages share 99% nucleotide sequence identity over 97% of their ORFs, although an insertion was found in AltAD45-P1 and P2 and some regions were slightly more divergent. Despite the high overall sequence similarity among these four phages, the group with the insertion and the group without it, have different host ranges against the A. macleodii strains tested. The AltAD45-P1 to P4 phages have genes for DNA replication and transcription as well as structural genes, which are similar to the N4-like Podoviridae genus that is widespread in proteobacteria. However, in terms of their genomic structure, AltAD45-P1 to P4 differ from that of the N4-like phages. Some distinguishing features include the lack of a large virion encapsidated RNA polymerase gene, very well conserved among all the previously described N4-like phages, a single-stranded DNA binding protein and different tail protein genes. We conclude that the AltAD45 phages characterized in this study constitute a new genus within the Podoviridae. PMID- 24228220 TI - What are the limitations on the wider therapeutic use of phage? AB - Bacterial resistance to antibiotics poses a serious health threat. Since research into new antibiotics is not progressing at the same rate as the development of bacterial resistance, widespread calls for alternatives to antibiotics have been made. Phage therapy is an ideal alternative candidate to be investigated. However the success of phage therapy may be hampered by a lack of investment support from large pharmaceutical companies, due to their narrow spectrum of activity in antibiotics, very large costs associated with clinical trials of the variety of phages needed, and regulatory requirements remaining unclear. Intellectual property is difficult to secure for therapeutic phage products for a variety of reasons, and patenting procedures vary widely between the US and the EU. Consequently, companies are more likely to invest in phage products for decontamination or veterinary use, rather than clinical use in humans. Some still raise questions as to the safety of phage therapy overall, suggesting the possibility of cytotoxicity and immunogenicity, depending on the phage preparation and route. On the other hand, with patients dying because of infections untreatable with conventional antibiotics, the question arises as to whether it is ethical not to pursue phage therapy more diligently. A paradigm shift about how phage therapy is perceived is required, as well as more rigorous proof of efficacy in the form of clinical trials of existing medicinal phage products. Phage therapy potential may be fulfilled in the meantime by allowing individual preparations to be used on a named-patient basis, with extensive monitoring and multidisciplinary team input. The National Health Service and academia have a role in carrying out clinical phage research, which would be beneficial to public health, but not necessarily financially rewarding. PMID- 24228222 TI - Life in Science: Richard Calendar. PMID- 24228221 TI - Enzymatic characterization of a lysin encoded by bacteriophage EL. AB - The bacteriophage EL is a virus that specifically attacks the human pathogen Pseudomonas aeruginosa. This phage carries a large genome that encodes for its own chaperonin which presumably facilitates the proper folding of phage proteins independently of the host chaperonin system. EL also encodes a lysin enzyme, a critical component of the lytic cycle that is responsible for digesting the peptidoglycan layer of the host cell wall. Previously, this lysin was believed to be a substrate of the chaperonin encoded by phage EL. In order to characterize the activity of the EL lysin, and to determine whether lysin activity is contingent on chaperonin-mediated folding, a series of peptidoglycan hydrolysis activity assays were performed. Results indicate that the EL-encoded lysin has similar enzymatic activity to that of the Gallus gallus lysozyme and that the EL lysin folds into a functional enzyme in the absence of phage chaperonin and should not be considered a substrate. PMID- 24228223 TI - Lytic bacteriophages: Potential interventions against enteric bacterial pathogens on produce. AB - Foodborne illnesses resulting from the consumption of produce commodities contaminated with enteric pathogens continue to be a significant public health issue. Lytic bacteriophages may provide an effective and natural intervention to reduce bacterial pathogens on fresh and fresh-cut produce commodities. The use of multi-phage cocktails specific for a single pathogen has been most frequently assessed on produce commodities to minimize the development of bacteriophage insensitive mutants (BIM) in target pathogen populations. Regulatory approval for the use of several lytic phage products specific for bacterial pathogens such as Escherichia coli O157:H7, Salmonella spp. and Listeria monocytogenes in foods and on food processing surfaces has been granted by various agencies in the US and other countries, possibly allowing for the more widespread use of bacteriophages in the decontamination of fresh and minimally processed produce. Research studies have shown lytic bacteriophages specific for E. coli O157:H7, Salmonella spp. and Listeria monocytogenes have been effective in reducing pathogen populations on leafy greens, sprouts and tomatoes. PMID- 24228224 TI - The moonlighting function of bacteriophage P4 capsid protein, Psu, as a transcription antiterminator. AB - Psu, a 20-kD bacteriophage P4 capsid decorating protein moonlights as a transcription antiterminator of the Rho-dependent termination. Psu forms specific complex with E.coli Rho protein, and affects the latter's ATP-dependent translocase activity along the nascent RNA. It forms a unique knotted dimer to take a V-shaped structure. The C-terminal helix of Psu makes specific contacts with a disordered region of Rho, encompassing the residues 139-153. An energy minimized structural model of the Rho-Psu complex reveals that the V-shaped Psu dimer forms a lid over the central channel of the Rho hexamer. This configuration of Psu causes a mechanical impediment to the translocase activity of Rho. The knowledge of structural and mechanistic basis of inhibition of Rho action by Psu may help to design peptide inhibitors for the conserved Rho-dependent transcription termination process of bacteria. PMID- 24228225 TI - Life in Science: Armin Dale Kaiser. PMID- 24228226 TI - Bacteriophages lytic for Salmonella rapidly reduce Salmonella contamination on glass and stainless steel surfaces. AB - A cocktail of six lytic bacteriophages, SalmoFreshTM, significantly (p < 0.05) reduced the number of surface-applied Salmonella Kentucky and Brandenburg from stainless steel and glass surfaces by > 99% (2.1-4.3 log). Both strains were susceptible to SalmoFreshTM in the spot-test assay. Conversely, SalmoFreshTM was unable to reduce surface contamination with a Salmonella Paratyphi B strain that was not susceptible to the phage cocktail in the spot-test assay. However, by replacing two SalmoFreshTM component phages with two new phages capable of lysing the Paratyphi B strain in the spot-test assay, the target range of the cocktail was shifted to include the Salmonella Paratyphi B strain. The modified cocktail, SalmoLyseTM, was able to significantly (p < 0.05) reduce surface contamination of the Paratyphi B strain by > 99% (2.1-4.1 log). The data show that both phage cocktails were effective in significantly reducing the levels of Salmonella on hard surfaces, provided the contaminating strains were susceptible in the spot test (i.e., spot-test susceptibility was indicative of efficacy in subsequent surface decontamination studies). The data also support the concept that phage preparations can be customized to meet the desired antibacterial application. PMID- 24228227 TI - Innate and acquired bacteriophage-mediated immunity. AB - We recently described a novel, non-host-derived, phage-mediated immunity active at mucosal surfaces, the main site of pathogen entry in metazoans. In that work, we showed that phage T4 adheres to mucus glycoproteins via immunoglobulin-like domains displayed on its capsid. This adherence positions the phage in mucus surfaces where they are more likely to encounter and kill bacteria, thereby benefiting both the phage and its metazoan host. We presented this phage-metazoan symbiosis based on an exclusively lytic model of phage infection. Here we extend our bacteriophage adherence to mucus (BAM) model to consider the undoubtedly more complex dynamics in vivo. We hypothesize how mucus-adherent phages, both lytic and temperate, might impact the commensal microbiota as well as protect the metazoan epithelium from bacterial invasion. We suggest that BAM may provide both an innate and an acquired antimicrobial immunity. PMID- 24228228 TI - Identification of new prognostic biomarkers for Stage III metastatic melanoma patients. AB - Accurately predicting disease outcome among patients bearing Stage III metastatic melanoma is complex. However, current advances in personalized medicine call for ever more precise prognostic assessments, as these have a significant impact not only on the design and analysis of clinical trials, but also on therapeutic decision-making. PMID- 24228229 TI - Strategies to improve the immunogenicity of anticancer vaccines based on dendritic cell/malignant cell fusions. AB - The rationale for fusing dendritic cells (DCs) with whole tumor cells to generate anticancer vaccines resides in the fact that the former operate as potent antigen presenting cells, whereas the latter express a constellation of tumor-associated antigens (TAAs). Although the administration of DC/malignant cell fusions to cancer patients is safe and this immunotherapeutic intervention triggers efficient tumor-specific T-cell responses in vitro, a limited number of objective clinical responses to DC/cancer cell fusions has been reported thus far. This review discusses novel approaches to improve the immunogenicity of DC/malignant cell fusions as anticancer vaccines. PMID- 24228230 TI - Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes. AB - T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were in the range of 1-17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8+ TILs differed from that of circulating CD8+ T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8+ RCC-infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8+ TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T cell clonotypes. PMID- 24228231 TI - Early onset and enhanced growth of autochthonous mammary carcinomas in C3 deficient Her2/neu transgenic mice. AB - Aside from its classical role in fighting infections, complement is an important, although poorly understood, component of the tumor microenvironment. In particular, the tumor growth-regulatory activities of complement remain under debate. To assess the role of the complement system in the progression of autochthonous mammary carcinomas, we have crossed complement component 3 (C3) deficient (C3-/- ) BALB/c male mice with BALB/c females expressing the activated rat Her2/neu oncogene (neuT). Although neuT transgenic mice develop spontaneous mammary cancers with 100% penetrance, a significantly shorter tumor latency (i.e., earlier onset of the first palpable tumor), a higher frequency of multiple tumors (multiplicity), and a dramatic increase in the tumor growth rate were found in neuT-C3-/- animals. The accelerated tumor onset observed in neuT-C3-/- mice was paralleled by an earlier onset of spontaneous lung metastases and by an increase in Her2 expression levels, primarily on the surface of tumor cells. The percentage of immune cells infiltrating neuT carcinomas was similar in C3 deficient and C3-proficient mice, with the exception of a significant increase in the frequency of regulatory T cells in neuT-C3-/- tumors. Of particular interest, the enhanced immunosuppression imparted by C3 deficiency clearly influenced the immunogenic phenotype of autochthonous mammary tumors as neuT-C3-/- malignant cells transplanted into syngeneic immunocompetent hosts gave rise to lesions with a significantly delayed kinetics and reduced incidence as compared with cells obtained from neuT C3-proficient tumors. Finally, increased blood vessel permeability was evident in neuT-C3-/- tumors, although a similar number of tumor vessels was found in neuT and neuT-C3-/- lesions. Altogether, these data suggest that complement plays a crucial role in the immunosurveillance and, possibly, the immunoediting of Her2-driven autochthonous mammary tumors. PMID- 24228232 TI - Zinc supplementation is required for the cytotoxic and immunogenic effects of chemotherapy in chemoresistant p53-functionally deficient cells. AB - Optimal tumor eradication often results from the death of malignant cells, as induced by chemotherapeutic agents, coupled to the induction of antitumor immune responses. However, cancer cells frequently become resistant to the cytotoxic activity of chemotherapy. The aim of the present study was to evaluate whether zinc dichloride (ZnCl2), which was known to re-establish the chemosensitivity of cancer cells by reactivating p53, promotes immunogenic instances of cell death. We found that ZnCl2, in combination with chemotherapeutic agents such as cisplatin and adriamycin (ADR), favors the apoptotic demise of chemoresistant cells, while cisplatin and ADR alone fail to do so. The co-culture of immature dendritic cells (DCs) with cancer cells succumbing to the co-administration of chemotherapy and ZnCl2 led to DC activation, as indicated by the upregulation of the activation markers CD83 and CD86. In part, such process depended on cell death, as it was limited (but not abrogated) by the pan-caspase inhibitor Z-VAD fmk. Moreover, DC activation relied on the ZnCl2-induced exposure of calreticulin (CRT) on the surface of cancer cells, correlating with the phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), a marker of endoplasmic reticulum stress. The siRNA-mediated knockdown of CRT as well as the inhibition of CRT exposure with brefeldin A strongly impaired DC maturation, indicating CRT translocation as induced by that ZnCl2 is a key event in this setting. Altogether, these results suggest that ZnCl2, has the potential to enhance the therapeutic effects of antineoplastic agents not only by improving their cytotoxic activity but also by promoting CRT exposure. PMID- 24228234 TI - Reader's Forum. PMID- 24228233 TI - IL-18-based combinatorial adjuvants promote the intranodal production of CCL19 by NK cells and dendritic cells of cancer patients. AB - The effective accumulation and interaction of mature dendritic cells (DCs) and naive T cells within lymph nodes (LNs), which are driven by the CCR7-CCL19/CCL21 chemokine axis, are critical for the induction of adaptive T-cell immunity. Human natural killer (NK) cells activated by interleukin (IL)-18 exhibit a unique 'helper' activity in promoting productive DC-T cell interactions, inducing DC maturation and shifting DC-primed T-cell responses toward a TH1 polarization. Here, we demonstrate that such IL-18-activated 'helper' NK cells uniquely stimulate DCs to produce high levels of CCL19 through tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma), a process that relies on secondary NK cell activation by additional inflammatory signals including IFNalpha, IL-15, IL 12 and IL-2. DCs activated by helper NK cells not only promote the efficient CCR7 mediated recruitment of naive CD8+ T cells, but also stimulate their expansion and expression of granzyme B. Using an ex vivo explant culture system based on LNs isolated from colorectal cancer patients, we found that CCL19 is upregulated in human tumor-associated lymphoid tissues treated with helper NK cell stimulating factors. Our findings demonstrate the ability of 2 signal-activated helper NK cells to promote the production of the DC- and naive/memory T cell attracting chemokine CCL19 in LNs, and provide a rationale for the therapeutic application of IL-18-containing 'combinatorial adjuvants' to facilitate the induction of antitumor immune responses. PMID- 24228235 TI - Comparison of the condyle-fossa relationship between skeletal class III malocclusion patients with and without asymmetry: a retrospective three dimensional cone-beam computed tomograpy study. AB - OBJECTIVE: This study investigated whether temporomandibular joint (TMJ) condyle fossa relationships are bilaterally symmetric in class III malocclusion patients with and without asymmetry and compared to those with normal occlusion. The hypothesis was a difference in condyle-fossa relationships exists in asymmetric patients. METHODS: Group 1 comprised 40 Korean normal occlusion subjects. Groups 2 and 3 comprised patients diagnosed with skeletal class III malocclusion, who were grouped according to the presence of mandibular asymmetry: Group 2 included symmetric mandibles, while group 3 included asymmetric mandibles. Pretreatment three-dimensional cone-beam computed tomography (3D CBCT) images were obtained. Right- and left-sided TMJ spaces in groups 1 and 2 or deviated and non-deviated sides in group 3 were evaluated, and the axial condylar angle was compared. RESULTS: The TMJ spaces demonstrated no significant bilateral differences in any group. Only group 3 had slightly narrower superior spaces (p < 0.001). The axial condylar angles between group 1 and 2 were not significant. However, group 3 showed a statistically significant bilateral difference (p < 0.001); toward the deviated side, the axial condylar angle was steeper. CONCLUSIONS: Even in the asymmetric group, the TMJ spaces were similar between deviated and non-deviated sides, indicating a bilateral condyle-fossa relationship in patients with asymmetry that may be as symmetrical as that in patients with symmetry. However, the axial condylar angle had bilateral differences only in asymmetric groups. The mean TMJ space value and the bilateral difference may be used for evaluating condyle-fossa relationships with CBCT. PMID- 24228236 TI - Effect of bite force on orthodontic mini-implants in the molar region: Finite element analysis. AB - OBJECTIVE: To examine the effect of bite force on the displacement and stress distribution of orthodontic mini-implants (OMIs) in the molar region according to placement site, insertion angle, and loading direction. METHODS: Five finite element models were created using micro-computed tomography (microCT) images of the maxilla and mandible. OMIs were placed at one maxillary and two mandibular positions: between the maxillary second premolar and first molar, between the mandibular second premolar and first molar, and between the mandibular first and second molars. The OMIs were inserted at angles of 45 degrees and 90 degrees to the buccal surface of the cortical bone. A bite force of 25 kg was applied to the 10 occlusal contact points of the second premolar, first molar, and second molar. The loading directions were 0 degrees , 5 degrees , and 10 degrees to the long axis of the tooth. RESULTS: With regard to placement site, the displacement and stress were greatest for the OMI placed between the mandibular first molar and second molar, and smallest for the OMI placed between the maxillary second premolar and first molar. In the mandibular molar region, the angled OMI showed slightly less displacement than the OMI placed at 90 degrees . The maximum Von Mises stress increased with the inclination of the loading direction. CONCLUSIONS: These results suggest that placement of OMIs between the second premolar and first molar at 45 degrees to the cortical bone reduces the effect of bite force on OMIs. PMID- 24228237 TI - Evaluation of the relationship between upper incisor exposure and cephalometric variables in Korean young adults. AB - OBJECTIVE: The purpose of this study was to classify Korean young adults into 3 groups on the basis of upper incisor exposure rates (UIERs) and to compare the skeletal, dental, and soft tissue variables. METHODS: Samples were obtained from 127 students at the College of Dentistry, Wonkwang University in South Korea. Facial photographs of frontal posed smiles and lateral cephalograms of the subjects were taken. The subjects were divided into 3 groups on the basis of UIERs and 20 measurements were compared among the 3 groups. The correlations between the variables were determined. RESULTS: Male and female subjects showed significant differences in the group distribution. Male subjects showed higher frequencies of low smiles, and female subjects showed higher frequencies of high smiles. The vertical height of the anterior alveolar process of the maxilla directly correlated with the UIER. However, the UIER showed no significant correlation with the vertical height of the anterior basal bone or the inclination of the upper incisor axis. In female subjects, the upper central incisor clinical crown length showed an inverse correlation with the UIER. However, this variable showed no significant correlation with the UIER in male subjects. CONCLUSIONS: The UIER was directly correlated with the levator muscle activity of the upper lip and inversely correlated with the upper lip thickness, yet there was no correlation between the UIER and upper lip length at rest. PMID- 24228238 TI - Debonding forces of three different customized bases of a lingual bracket system. AB - OBJECTIVE: The purpose of this study was to investigate whether extension of the custom base is necessary for enhancement of bond strength, by comparing the debonding forces and residual adhesives of 3 different lingual bracket systems. METHODS: A total of 42 extracted upper premolars were randomly divided into 3 groups of 14 each for bonding with brackets having (1) a conventional limited resin custom base; (2) an extended gold alloy custom base: IncognitoTM; and (3) an extended resin custom base: KommonBaseTM. The bonding area was measured by scanning the bracket bases with a 3-dimensional digital scanner. The debonding force was measured with an Instron universal testing machine, which applied an occlusogingival shear force. RESULTS: The mean debonding forces were 60.83 N (standard deviation [SD] 10.12), 69.29 N (SD 9.59), and 104.35 N (SD17.84) for the limited resin custom base, extended gold alloy custom base, and extended resin custom base, respectively. The debonding force observed with the extended resin custom base was significantly different from that observed with the other bases. In addition, the adhesive remnant index was significantly higher with the extended gold alloy custom base. CONCLUSIONS: All 3 custom-base lingual brackets can withstand occlusal and orthodontic forces. We conclude that effective bonding of lingual brackets can be obtained without extension of the custom base. PMID- 24228239 TI - Does the time interval after bleaching influence the adhesion of orthodontic brackets? AB - OBJECTIVE: To test the null hypothesis that no difference exists between the effects of at-home bleaching and in-office bleaching on shear bond strength (SBS) with bracket bonding at 4 different time intervals after dental bleaching. METHODS: Ninety extracted human premolars were randomly divided into 9 groups (n = 10) according to the bleaching methods used (at-home bleaching and in-office bleaching) and the storage time in artificial saliva (30 min, 1 day, 2 weeks, and 3 weeks before bonding). The control group was stored in artificial saliva for 7 days. Brackets were bonded with the Transbond XT adhesive system, and SBS testing was performed. The adhesive remnant index (ARI) was used to assess the amount of resin remaining on the enamel surfaces after debonding. The SBS data were analyzed by analysis of variance (ANOVA) and the Tukey test. For the ARI, the Kruskal-Wallis test was performed. Significance for all statistical tests was predetermined to be p < 0.05. RESULTS: The SBS of the unbleached group was significantly higher (p < 0.05) than that of the bleached groups (except for the group bonded 30 min after at-home bleaching). CONCLUSIONS: The null hypothesis was not totally rejected. All bleaching groups tested had decreased SBS of the brackets to the enamel, except for the group bonded 30 min after at-home bleaching. The SBS returned to values close to those of the unbleached enamel within 3 weeks following bleaching. PMID- 24228240 TI - Orthodontic and surgical management of cleidocranial dysplasia. AB - Cleidocranial dysplasia (CCD), an autosomal dominant disorder with a prevalence of 1 in 1,000,000 individuals, is mainly caused by mutations in Runx2, a gene required for osteoblastic differentiation. It is generally characterized by hypoplastic clavicles, narrow thorax, and delayed or absent fontanel closure. Importantly, its orofacial manifestations, including midfacial hypoplasia, retained primary teeth, and impacted permanent and supernumerary teeth, severely impede the well-being of affected individuals. Successful treatment of the orofacial problems requires the combined efforts of dental specialists. However, only a few successfully treated cases have been reported because of the rarity of CCD and complexity of the treatment. This article presents the University of California, San Francisco (UCSF) treatment protocol for the dentofacial manifestations of CCD based on two treated and 17 diagnosed cases. The records of two patients with CCD who had been treated at the UCSF School of Dentistry and the treatment options reported in the literature were reviewed. The UCSF treatment protocol produced a successful case and a partially successful one (inadequate oral hygiene in the retention stage resulted in decay and loss of teeth). It provides general guidelines for successfully treating the orofacial manifestations of CCD. PMID- 24228241 TI - The world bacterial biogeography and biodiversity through databases: a case study of NCBI Nucleotide Database and GBIF Database. AB - Databases are an essential tool and resource within the field of bioinformatics. The primary aim of this study was to generate an overview of global bacterial biodiversity and biogeography using available data from the two largest public online databases, NCBI Nucleotide and GBIF. The secondary aim was to highlight the contribution each geographic area has to each database. The basis for data analysis of this study was the metadata provided by both databases, mainly, the taxonomy and the geographical area origin of isolation of the microorganism (record). These were directly obtained from GBIF through the online interface, while E-utilities and Python were used in combination with a programmatic web service access to obtain data from the NCBI Nucleotide Database. Results indicate that the American continent, and more specifically the USA, is the top contributor, while Africa and Antarctica are less well represented. This highlights the imbalance of exploration within these areas rather than any reduction in biodiversity. This study describes a novel approach to generating global scale patterns of bacterial biodiversity and biogeography and indicates that the Proteobacteria are the most abundant and widely distributed phylum within both databases. PMID- 24228242 TI - Different contribution of splanchnic organs to hyperlactatemia in fecal peritonitis and cardiac tamponade. AB - BACKGROUND: Changes in hepatosplanchnic lactate exchange are likely to contribute to hyperlactatemia in sepsis. We hypothesized that septic and cardiogenic shock have different effects on hepatosplanchnic lactate exchange and its contribution to hyperlactatemia. MATERIALS AND METHODS: 24 anesthetized pigs were randomized to fecal peritonitis (P), cardiac tamponade (CT), and to controls (n = 8 per group). Oxygen transport and lactate exchange were calculated during 24 hours. RESULTS: While hepatic lactate influx increased in P and in CT, hepatic lactate uptake remained unchanged in P and decreased in CT. Hepatic lactate efflux contributed 20% (P) and 33% (CT), respectively, to whole body venous efflux. Despite maintained hepatic arterial blood flow, hepatic oxygen extraction did not increase in CT. CONCLUSIONS: Whole body venous lactate efflux is of similar magnitude in hyperdynamic sepsis and in cardiogenic shock. Although jejunal mucosal pCO2 gradients are increased, enhanced lactate production from other tissues is more relevant to the increased arterial lactate. Nevertheless, the liver fails to increase hepatic lactate extraction in response to rising hepatic lactate influx, despite maintained hepatic oxygen consumption. In cardiac tamponade, regional, extrasplanchnic lactate production is accompanied by hepatic failure to increase oxygen extraction and net hepatic lactate output, despite maintained hepatic arterial perfusion. PMID- 24228243 TI - Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: is this a possible reason for unexplained spontaneous abortion? AB - Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies. PMID- 24228244 TI - SNP rs2073618 of the osteoprotegerin gene is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes. AB - Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26-5.13, P = 0.01). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR. PMID- 24228245 TI - Biosynthesis of osmoregulated periplasmic glucans in Escherichia coli: the phosphoethanolamine transferase is encoded by opgE. AB - Osmoregulated periplasmic glucans (OPGs) are oligosaccharides found in the periplasm of many Gram-negative bacteria. Glucose is the sole constitutive sugar and this backbone may be substituted by various kinds of molecules depending on the species. In E. coli, OPG are substituted by phosphoglycerol and phosphoethanolamine derived from membrane phospholipids and by succinyl residues. In this study, we describe the isolation of the opgE gene encoding the phosphoethanolamine transferase by a screen previously used for the isolation of the opgB gene encoding the phosphoglycerol transferase. Both genes show structural and functional similarities without sequence similarity. PMID- 24228246 TI - Estimation of cutoff values of cotinine in urine and saliva for pregnant women in Poland. AB - Setting appropriate cutoff values and the use of a highly sensitive analytical method allow for correct classification of the smoking status. Urine-saliva pairs samples of pregnant women in the second and third trimester, and saliva only in the first trimester were collected. Offline SPE and LC-ESI-MS/MS method was developed in the broad concentration range (saliva 0.4-1000 ng/mL, urine 0.8-4000 ng/mL). The mean recoveries were 3.7 +/- 7.6% for urine and 99.1 +/- 2.6% for saliva. LOD for saliva was 0.12 ng/mL and for urine 0.05 ng/mL; LOQ was 0.4 ng/mL and 0.8 ng/mL, respectively. Intraday and interday precision equaled, respectively, 1.2% and 3.4% for urine, and 2.3% and 6.4% for saliva. There was a strong correlation between salivary cotinine and the uncorrected cotinine concentration in urine in the second and third trimesters of pregnancy. The cutoff values were established for saliva 12.9 ng/mL and urine 42.3 ng/mL or 53.1 MUg/g creatinine with the ROC curve analysis. The developed analytical method was successfully applied to quantify cotinine, and a significant correlation between the urinary and salivary cotinine levels was found. The presented cut-off values for salivary and urinary cotinine ensure a categorization of the smoking status among pregnant women that is more accurate than self-reporting. PMID- 24228248 TI - A review for detecting gene-gene interactions using machine learning methods in genetic epidemiology. AB - Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs), support vector machine (SVM), and random forests (RFs) in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease. PMID- 24228247 TI - The treatment outcome and radiation-induced toxicity for patients with head and neck carcinoma in the IMRT era: a systematic review with dosimetric and clinical parameters. AB - A descriptive analysis was made in terms of the related radiation induced acute and late mucositis and xerostomia along with survival and tumor control rates (significance level at 0.016, bonferroni correction), for irradiation in head and neck carcinomas with either 2D Radiation Therapy (2DRT) and 3D conformal (3DCRT) or Intensity Modulated Radiation Therapy (IMRT). The mean score of grade > II xerostomia for IMRT versus 2-3D RT was 0.31 +/- 0.23 and 0.56 +/- 0.23, respectively (Mann Whitney, P < 0.001). The parotid-dose for IMRT versus 2-3D RT was 29.56 +/- 5.45 and 50.73 +/- 6.79, respectively (Mann Whitney, P = 0.016). The reported mean parotid-gland doses were significantly correlated with late xerostomia (spearman test, rho = 0.5013, P < 0.001). A trend was noted for the superiority of IMRT concerning the acute oral mucositis. The 3-year overall survival for either IMRT or 2-3DRT was 89.5% and 82.7%, respectively (P = 0.026, Kruskal-Wallis test). The mean 3-year locoregional control rate was 83.6% (range: 70-97%) and 74.4 (range: 61-82%), respectively (P = 0.025, Kruskal-Wallis). In conclusion, no significant differences in terms of locoregional control, overall survival and acute mucositis could be noted, while late xerostomia is definitely higher in 2-3D RT versus IMRT. Patients with head and neck carcinoma should be referred preferably to IMRT techniques. PMID- 24228249 TI - In silico modeling and functional interpretations of Cry1Ab15 toxin from Bacillus thuringiensis BtB-Hm-16. AB - The theoretical homology based structural model of Cry1Ab15 delta-endotoxin produced by Bacillus thuringiensis BtB-Hm-16 was predicted using the Cry1Aa template (resolution 2.25 A). The Cry1Ab15 resembles the template structure by sharing a common three-domain extending conformation structure responsible for pore-forming and specificity determination. The novel structural differences found are the presence of beta0 and alpha3, and the absence of alpha7b, beta1a, alpha10a, alpha10b, beta12, and alpha11a while alpha9 is located spatially downstream. Validation by SUPERPOSE and with the use of PROCHECK program showed folding of 98% of modeled residues in a favourable and stable orientation with a total energy Z-score of -6.56; the constructed model has an RMSD of only 1.15 A. These increments of 3D structure information will be helpful in the design of domain swapping experiments aimed at improving toxicity and will help in elucidating the common mechanism of toxin action. PMID- 24228250 TI - A neural network model can explain ventriloquism aftereffect and its generalization across sound frequencies. AB - Exposure to synchronous but spatially disparate auditory and visual stimuli produces a perceptual shift of sound location towards the visual stimulus (ventriloquism effect). After adaptation to a ventriloquism situation, enduring sound shift is observed in the absence of the visual stimulus (ventriloquism aftereffect). Experimental studies report opposing results as to aftereffect generalization across sound frequencies varying from aftereffect being confined to the frequency used during adaptation to aftereffect generalizing across some octaves. Here, we present an extension of a model of visual-auditory interaction we previously developed. The new model is able to simulate the ventriloquism effect and, via Hebbian learning rules, the ventriloquism aftereffect and can be used to investigate aftereffect generalization across frequencies. The model includes auditory neurons coding both for the spatial and spectral features of the auditory stimuli and mimicking properties of biological auditory neurons. The model suggests that different extent of aftereffect generalization across frequencies can be obtained by changing the intensity of the auditory stimulus that induces different amounts of activation in the auditory layer. The model provides a coherent theoretical framework to explain the apparently contradictory results found in the literature. Model mechanisms and hypotheses are discussed in relation to neurophysiological and psychophysical data. PMID- 24228251 TI - Paired measurements of paraoxonase 1 and serum amyloid A as useful disease markers. AB - Paraoxonase 1 (PON1) and serum amyloid A (SAA) are proteins carried by high density lipoprotein (HDL) particles. Among the HDL-associated protein molecules, SAA, an inflammation-related marker, and PON1, an antioxidant marker, tend to change in relatively clear opposite directions in physiological situations. In clinical chemistry, paired measurements of both markers may provide useful information to understand dysfunctional HDL in diseases with inflammation and oxidative stress conditions. Actually, limited clinical studies have suggested that the combined use of PON1 and SAA may be a tool for observing the pathophysiology of some disease entities. From the findings of experimental studies, PON1 appears to be cooperatively regulated by inflammation- and oxidative stress-related molecules linked with SAA regulation in humans. More studies remain to be performed to ascertain the value of paired measurements of both promising markers in clinical practice. PMID- 24228252 TI - Pulmonary hypertension in Portugal: first data from a nationwide registry. AB - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. METHODS: We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). RESULTS: Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 +/- 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 +/- 5.9 mmHg) and mean pulmonary vascular resistance (11.4 +/ 6.5 Wood units), with a low cardiac index (2.7 +/- 1.1 L.min(-1).m(-2)); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 +/- 12.5 years) and had higher RAP (11.0 +/- 5.2 mmHg, P = 0.015). CONCLUSIONS: We describe for the first time nationwide data on the diagnosis, management, and prognosis of PAH and CTEPH patients in Portugal. Clinical presentation and outcomes are comparable with those reported on other national registries. PMID- 24228253 TI - Risk prediction models for mortality in community-acquired pneumonia: a systematic review. AB - BACKGROUND: Several models have been developed to predict the risk of mortality in community-acquired pneumonia (CAP). This study aims to systematically identify and evaluate the performance of published risk prediction models for CAP. METHODS: We searched MEDLINE, EMBASE, and Cochrane library in November 2011 for initial derivation and validation studies for models which predict pneumonia mortality. We aimed to present the comparative usefulness of their mortality prediction. RESULTS: We identified 20 different published risk prediction models for mortality in CAP. Four models relied on clinical variables that could be assessed in community settings, with the two validated models BTS1 and CRB-65 showing fairly similar balanced accuracy levels (0.77 and 0.72, resp.), while CRB 65 had AUROC of 0.78. Nine models required laboratory tests in addition to clinical variables, and the best performance levels amongst the validated models were those of CURB and CURB-65 (balanced accuracy 0.73 and 0.71, resp.), with CURB-65 having an AUROC of 0.79. The PSI (AUROC 0.82) was the only validated model with good discriminative ability among the four that relied on clinical, laboratorial, and radiological variables. CONCLUSIONS: There is no convincing evidence that other risk prediction models improve upon the well-established CURB 65 and PSI models. PMID- 24228254 TI - Systems approaches to modeling chronic mucosal inflammation. AB - The respiratory mucosa is a major coordinator of the inflammatory response in chronic airway diseases, including asthma and chronic obstructive pulmonary disease (COPD). Signals produced by the chronic inflammatory process induce epithelial mesenchymal transition (EMT) that dramatically alters the epithelial cell phenotype. The effects of EMT on epigenetic reprogramming and the activation of transcriptional networks are known, its effects on the innate inflammatory response are underexplored. We used a multiplex gene expression profiling platform to investigate the perturbations of the innate pathways induced by TGF beta in a primary airway epithelial cell model of EMT. EMT had dramatic effects on the induction of the innate pathway and the coupling interval of the canonical and noncanonical NF- kappa B pathways. Simulation experiments demonstrate that rapid, coordinated cap-independent translation of TRAF-1 and NF- kappa B2 is required to reduce the noncanonical pathway coupling interval. Experiments using amantadine confirmed the prediction that TRAF-1 and NF- kappa B2/p100 production is mediated by an IRES-dependent mechanism. These data indicate that the epigenetic changes produced by EMT induce dynamic state changes of the innate signaling pathway. Further applications of systems approaches will provide understanding of this complex phenotype through deterministic modeling and multidimensional (genomic and proteomic) profiling. PMID- 24228255 TI - Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. AB - Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL. PMID- 24228256 TI - Ouabain-induced apoptosis in cochlear hair cells and spiral ganglion neurons in vitro. AB - Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochlea in vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabain in vivo varied among mammalian species. Little is known about the ototoxic effects in vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 MUM for different time to elucidate the ototoxic effects of ouabain in vitro and to provide insights that could explain the comparative ototoxic effects of ouabain in vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damage in vitro was dose and time dependent. 500 MUM ouabain and 1000 MUM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways. PMID- 24228257 TI - Facilitating ambulatory electronic health record system implementation: evidence from a qualitative study. AB - BACKGROUND: Ambulatory care practices have increasing interest in leveraging the capabilities of electronic health record (EHR) systems, but little information is available documenting how organizations have successfully implemented these systems. Objective. To characterize elements of successful electronic health record (EHR) system implementation and to synthesize the key informants' perspectives about successful implementation practices. METHODS: Key informant interviews and focus groups were conducted with a purposive sample of individuals from US healthcare organizations identified for their success with ambulatory EHR implementation. Rigorous qualitative data analyses used both deductive and inductive methods. RESULTS: Participants identified personal and system-related barriers, at both the individual and organization levels, including poor computer skills, productivity losses, resistance to change, and EHR system failure. Implementation success was reportedly facilitated by careful planning and consistent communication throughout distinct stages of the implementation process. A significant element of successful implementation was an emphasis on optimization, both during "go-live" and, subsequently, when users had more experience with the system. CONCLUSION: Successful EHR implementation requires both detailed planning and clear mechanisms to deal with unforeseen or unintended consequences. Focusing on user buy-in early and including plans for optimization can facilitate greater success. PMID- 24228258 TI - Do fallers and nonfallers equally benefit from balance specific exercise program? A pilot study. AB - The purpose of the study was to determine the sample size that would allow broad generalizability of the results. To investigate the differences in the responsiveness of fallers and nonfallers to a multicomponent functional balance specific program, 23 participating subjects (70.1 +/- 6.6 years) were divided into nonfallers group (13) and fallers group (10). The components of the balance specific program were (1) changing of the center of gravity (CoG) in the vertical direction, (2) shifting of the CoG to the border of stability, (3) rotation of the head and body about the vertical axis, (4) standing and walking on soft surface, and (5) walking over obstacles or on a narrow path. At the end of eight months of the training program, there was no significant difference between the two groups regarding postural sway. The total center of pressure path length was used as the principal outcome measure for the sample size calculation. Based on these results the a priori sample size calculation yielded the estimate of 110 subjects required to be enrolled in order to get 20 subjects in fallers and 30 subjects in nonfallers group for the 80% power to detect the results as significant. PMID- 24228260 TI - Antioxidant, lipid lowering, and membrane stabilization effect of sesamol against doxorubicin-induced cardiomyopathy in experimental rats. AB - The present study was designed to evaluate the cardioprotective effect of sesamol against doxorubicin-induced cardiomyopathy in rats. In this study, the cardioprotective effect of sesamol against doxorubicin induced cardiomyopathy in experimental rats was evaluated at the dosage of 50 mg/kg bw. Doxorubicin was administered to rats at a total cumulative dose of 15 mg/kg through intraperitoneal route for 2 weeks in six-divided dose on 8th, 10th, 14th, 16th, 18th, and 21st day. After the last dose administration, the endogenous antioxidants and lipid peroxidation were estimated in heart tissue homogenate. Cardiac biomarkers such as troponin T, LDH, CK, and AST and lipid profiles such as cholesterol, triglycerides, HDL, LDL, and VLDL were estimated in serum. Sesamol has cardioprotective activity through normalization of doxorubicin induced-altered biochemical parameters. Biochemical study was further supported by histopathological study, which shows that sesamol offered myocardial protection from necrotic damage. From these findings, it has been concluded that the sesamol has significant cardioprotection against doxorubicin induced cardiomyopathy via amelioration of oxidative stress, lipid lowering, and membrane stabilization effect. PMID- 24228259 TI - Epidemiology and risk factors of tooth loss among Iranian adults: findings from a large community-based study. AB - OBJECTIVES: To investigate the prevalence of tooth loss and different prosthetic rehabilitations among Iranian adults, as well as the potential determinants of tooth loss. METHODS: In a cross-sectional community-based study conducted among 8094 Iranian adults living in Isfahan province, a self-administered questionnaire was used to assess epidemiologic features of tooth loss. RESULTS: Thirty-two percent of subjects had all their teeth, 58.6% had lost less than 6, and 7.2% of participants had lost more than 6 teeth. One hundred and sixty-nine individuals (2.2%) were edentulous. Among participants, 2.3% had single jaw removable partial denture, 3.6% had complete removable denture in both jaws, and 4.6% had fixed prosthesis. Others reported no prosthetic rehabilitation (89.5%). In the age subgroup analysis (<=35 and >35 years old) tooth loss was more prevalent among men than women (OR = 2.8 and 1.9, resp., P < 0.01). Also, in both age groups, current and former smokers had higher levels of tooth loss than nonsmokers (P < 0.001 and P < 0.05, resp.). In addition, tooth loss was positively related to metabolic abnormality for age group >35 years (adjusted OR = 1.29, P < 0.01). CONCLUSIONS: Tooth loss is highly prevalent in Iranian adult population. Community programs promoting oral health for prevention of tooth loss should be considered taking into account its major determinants including lower educational level, male gender, smoking, and metabolic abnormality. PMID- 24228261 TI - Hemizona assay and sperm penetration assay in the prediction of IVF outcome: a systematic review. AB - The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA's role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52-100%), specificity (0-100%), and PPV (18-100%) and NPV (0-100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75-100%), good specificity (57-100%), and high PPV (79-100%) and NPV (68-100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting. PMID- 24228263 TI - Serum lipid profiling of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma by ultra fast LC/IT-TOF MS. AB - In this study, an ultra fast LC/IT-TOF MS (UFLC/IT-TOF MS)-based serum lipidomics method was employed to characterize the serum lipid profile of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). After data collection and processing, 96 lipids including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, triacylglycerides, and cholesterol esters were identified and used for subsequent data analysis. Partial least squares discriminant analysis revealed that patients with liver diseases had distinctly different serum lipid profile from that of healthy controls; while cirrhosis and HCC patients had a similar serum lipid profile, but different from that of hepatitis patients. The ANOVA analysis found 75 of the 96 identified lipids to be abnormally regulated, among which most of these lipids were downregulated in cirrhosis and HCC patients compared with those of healthy controls and hepatitis patients, while hepatitis patients induced several lipids downregulated and others upregulated compared with those of healthy controls, indicating the aberrant lipid metabolism in patients with liver diseases. This work demonstrated the utility of UFLC/IT-TOF MS-based serum lipidomics as a powerful tool to investigate the lipid metabolism of liver diseases. PMID- 24228262 TI - Yield and cost of performing screening tests for constipation in children. AB - BACKGROUND: Chronic constipation is one of the most common reasons for pediatric outpatient visits. Clinical guidelines recommend that the work-up for chronic refractory constipation include thyroid function tests, celiac serology, and measurement of calcium and lead levels. Data to justify routine screening of constipated children using these laboratory tests are lacking. OBJECTIVES: To study the prevalence of celiac disease, hypothyroidism, hypercalcemia and lead poisoning in children with chronic constipation; and to estimate the health care costs of applying the guideline recommendations. METHOD: Charts of constipated children from 2007 to 2011 were reviewed for the present retrospective cohort study. Results and costs of thyroid function tests, celiac panel, total immunoglobulin (Ig) A, and determination of lead and calcium levels were analyzed. RESULTS: A total of 7472 children (mean age 7.9 years; 3908 female) were evaluated: 1731 patients were screened for celiac antibodies; 55 had elevated tissue transglutaminase IgA levels and 29 had biopsy-positive celiac disease. Only three celiac patients had constipation as the sole presenting symptom; 1703 patients were screened for total IgA levels; 55 had IgA deficiency and two had biopsy-positive celiac disease; 2332 had free T4 and/or thyroid stimulating hormone levels; and 14 had hypothyroidism. Only two patients had constipation as the sole presenting symptom; 4651 patients had calcium levels measured, 10 of whom had high levels but normal repeat values. Three patients had normal lead levels. The mean cost per patient was USD$1,014. Total screening cost for all patients was USD$4.7 million. CONCLUSION: Constipation alone did not increase the likelihood of celiac disease or hypothyroidism above the population prevalence. No benefit of screening for hypercalcemia was found. High health care costs were associated with the use of screening tests for organic constipation. PMID- 24228264 TI - Differences and similarities between LC-MS derived serum fingerprints of patients with B-cell malignancies. AB - Multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) are closely related B-cell non-Hodgkin's lymphomas. MM, a plasma cell malignancy, is the second most common haematopoietic cancer in Western countries, with the median survival time of 3-4 years. CLL, a lymphocyte B malignancy, is the most common leukaemia in Western countries. About 25-30% of all CLL patients do not survive the period of 5 years following diagnosis. Both malignancies are complicated, not fully understood and incurable with the current standard treatment. Biologically, MM and CLL may be preceded by associated precursor conditions, that is, monoclonal gammopathy of undetermined significance for MM and its cellular counterpart and monoclonal B-cell lymphocytosis for CLL. Similarities and differences in the biology of these malignancies prompted us to evaluate their metabolomics in stages requiring chemotherapy. Fingerprinting of serum metabolites by the use of LC-MS has never been applied in studies on MM and CLL patients. Obtained results revealed metabolites common for both malignancies (e.g. fatty acids, acylcarnitines, sphingolipids, phospholipids, phenylalanylphenylalanine and isoprene) as well as those which render them different (e.g. lysophosphatidylcholines, monoacylglycerols, aminocaproic acid, phenylacetylglutamine). PMID- 24228265 TI - Targeted analysis of omega-6-derived eicosanoids in human serum by SPE-LC-MS/MS for evaluation of coronary artery disease. AB - A targeted approach has been applied to quantitative analysis of eicosanoids derived from omega-6 fatty acids in serum from individuals diagnosed with coronary artery disease (CAD). The target metabolites were series-2 prostaglandins, thromboxane B2, hydroxyeicosatetraenoic acids, and hydroxyoctadecadienoic acids. The method was based on SPELC-MS/MS in selected reaction monitoring mode for highly selective and sensitive determination of the target eicosanoids. The combination of SPE and LC-MS/MS involved the benefits from both direct analysis of serum without a step for protein precipitation and fully automation of the analysis. The method allowed comparison of omega-6 derived eicosanoids in serum from patients diagnosed with CAD and from control individuals. The effect of treatment with aspirin on the profile of the target compounds was evaluated through its incidence on the different pathways. Finally, the serum levels of the target metabolites in patients diagnosed with CAD were also statistically examined according to the severity of the coronary lesion stratified as stable angina, non-ST-elevation acute coronary syndrome, and acute myocardial infarction. PMID- 24228267 TI - Lipogranulomatosis and hypersplenism induced by ruptured silicone breast implants. PMID- 24228266 TI - Determination of changes in the metabolic profile of avocado fruits (Persea americana) by two CE-MS approaches (targeted and non-targeted). AB - A CZE method with two different MS detection conditions (MRM and Full Scan) was developed to determine qualitative and quantitative changes in the metabolic profile of avocado fruits (Persea americana). LODs in MRM approach were found between 20.1 and 203.0 ppb for abscisic acid and perseitol, respectively, whilst in Full Scan, varied within the range 0.22-1.90 ppm for the same metabolites. The RSDs for reproducibility test did not exceed 11.45%. The two MS approaches were used to quantify 10 metabolites (phenolic acids, flavonoids, a carbohydrate, an organic acid, a vitamin and a phytohormone) in 18 samples of avocado at different ripening states, and the achieved results were compared. Perseitol, quinic, chlorogenic, trans-cinnamic, pantothenic and abscisic acids, as well as epicatechin and catechin decreased during the ripening process, whereas ferulic and p-coumaric acids showed the opposite trend. Moreover, some other unknown compounds whose concentration changed largely during ripening were also studied by MS/MS and QTOF MS to get a tentative identification. PMID- 24228268 TI - Leptomeningeal metastases from primary plasma cell leukemia. PMID- 24228269 TI - Preface. cardiac and metabolic disorders in hemodialysis. PMID- 24228270 TI - 1H NMR-based metabonomic analysis of serum and urine in a nonhuman primate model of diabetic nephropathy. AB - Diabetic nephropathy (DN) is a serious metabolic disease, and comprehensive understanding of its complex mechanism will help in preventing the onset and progression of DN. To reveal the systemic metabolic changes associated with renal injury, we performed 1H NMR-based metabonomic and multivariate analyses to analyze serum and urine obtained from a nonhuman primate model of DN. Our results indicated that DN monkeys exhibited a distinct metabolic profile, including higher levels of VLDL/LDL, lipids, unsaturated lipids, uric acid, allantoin, fumarate and hippurate, as well as lower levels of HDL, alanine, glutamate, pyruvate, formate, tyrosine, histidine and NAD+. The disturbed metabolic pathways were further identified, including NAD+ metabolism, purine metabolism, oxidative stress, lipid metabolism, and renal tubular reabsorption. This study highlights that NMR-based metabonomics provides insight into the underlying pathways in the pathogenesis and progression of DN at the metabolic level. PMID- 24228271 TI - Reactivity of bridged pentelidene complexes with isonitriles: a new way to pentel containing heterocycles. AB - The reaction of [Cp*E{W(CO)5}2] (E=P (1a), As (1b); Cp*=1,2,3,4,5 pentamethylcyclopentadienyl) with isonitriles RNC (R=tBu, cyclohexyl (Cy), nBu) depends on the steric demand of the substituent at the isonitrile as well as on the stoichiometry of the starting materials. With tBuNC only the Lewis acid/base adducts [Cp*E{W(CO)5}2ACHTUNGTRENUNG(CNtBu)] (E=P (2a), As (2b)) are formed. The use of Cy and n-butylisonitrile leads first to the formation of the Lewis acid/base adduct, but only at low temperatures. At ambient temperatures, a rearrangement occurs and bicycloACHTUNGTRENUNG[3.2.0]heptane derivatives of the type [{C(Me)CACHTUNGTRENUNG( CH2)C(Me)C(Me)C(Me)}C(NR)-E{W(CO)5}2] (E=P, As; R=Cy, nBu) (3a-Cy, 3b-Cy, 3a-nBu and 3b-nBu) are obtained. The use of a further equivalent of isonitrile results in products revealing two new structural motifs, the four-membered ring derivatives [CACHTUNGTRENUNG(Cp*)N(R)C(NR)E{W(CO)5}2] (4: E=P, As; R=Cy, nBu) and the bicyclic complexes [[{C(Me)CACHTUNGTRENUNG( CH2)C(Me)C(Me)C(Me)}C(NR)2-E{W(CO)5}2] (5: E=As; R=Cy). The reaction pathway depends on the substituent at the isonitrile. By treatment of 1a with two equivalents of CyNC only a 2H-1,3-azaphosphet complex 4a-Cy (E=P; R=Cy) is formed. Treatment of 1b with two equivalents of CyNC exclusively leads to the complex 5b-Cy (E=As; R=Cy). Treatment of 1a with two equivalents of nBuNC results in a mixture of complexes, the 2H-1,3-azaphosphet 4a-nBu (E=P; R=nBu) and the bicyclic complex 5a-nBu (E=P; R=nBu). For the arsenidene complex 1b a mixture of the 2H-1,3-azarsete complex 4b-nBu (E=As; R=nBu) and the bicyclic complex 5b-nBu (E=P, As; R=Cy, nBu) is obtained. Complex 4b-nBu is the first example of a 2H-1,3 azarsete complex. All products have been characterized by using mass spectrometry, NMR spectroscopy, and X-ray diffraction analysis. PMID- 24228272 TI - The Gynecologic Oncology Group (GOG) Report - July 2013. PMID- 24228273 TI - Retraction notice to "Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery" (J Clin Anesth 2006;18:422-6). PMID- 24228274 TI - Efficient volume reconstruction for parallel-beam computed laminography by filtered backprojection on multi-core clusters. AB - Computed laminography (CL) was developed to use X-rays from synchrotron sources for high-resolution imaging of the internal structure of a flat specimen from a series of 2-D projection images. The projections are acquired by irradiation of the sample under different rotation angles where the object rotation axis is inclined with respect to the beam direction. This yields for laterally extended objects a more uniform average transmitted intensity during sample rotation compared with computed tomography (CT). The reconstruction problem of CL cannot be reduced to a data-efficient 2-D case (as for parallel-beam CT) since each single slice perpendicular to the rotation axis requires a 2-D region on the detector as input data for all projection directions. This paper describes a computationally efficient reconstruction procedure based on filtered backprojection (FBP) adapted to the CL acquisition geometry. From the Fourier slice theorem, we derive a framework for analytic image reconstruction and outline implementation details of the generic FBP algorithm. Different approaches reducing the reconstruction time by means of parallel and distributed computations are considered and evaluated. PMID- 24228275 TI - Labeling Spain with Stanford. AB - We present an end-to-end framework for outdoor scene region decomposition, learned on a small set of randomly selected images that generalizes well to multiple data sets containing images from around the world. We discuss the different aspects of the framework especially a generalized variational inference method with better approximations to the true marginals of a graphical model. Experimentally, we explain why the framework is robust and performs competitively on many diverse scene data sets, including several unseen scene types. We have obtained high pixel-level accuracies (~ 80%) in three of the four data sets, which include a benchmark data set known as the Stanford background data set. Our model obtained over 70% accuracy on the fourth data set, which contained a number of indoor and close-up images that are significantly different from our training examples. PMID- 24228276 TI - Nokia and Alaska airlines: a tale of two snow country-based companies. How well are physician-group leaders anticipating where population health management is headed? PMID- 24228277 TI - Taking the population health plunge: physician organization leaders go big. PMID- 24228278 TI - ACO challenge: leveraging data for accountable care. Interview by Mark Hagland. PMID- 24228279 TI - What does a car look like? Looking at the health information exchange conundrum: a historical perspective. PMID- 24228280 TI - Health information exchange: are we at an inflection point? As health information exchange evolves forward, industry leaders and experts debate what to do about some of the continuing obstacles to granular-level data exchange. Should federal officials intervene? PMID- 24228281 TI - Advancing mobile computing: how one New Jersey group has moved forward. At the 15 physician Vanguard Medical Group in northeast New Jersey, PCMH participation helped spur a broader mobile strategy. PMID- 24228282 TI - HIEs see role as patient portal providers. HIE as possible alternative to patient portals. PMID- 24228283 TI - M.D. documentation: where the rubber meets the road. An emergency physician's perspective on technology as an enabler. Interview by Mark Hagland. PMID- 24228285 TI - People to know 2013: Meet 14 superstars making a difference in the diabetes world. PMID- 24228284 TI - Baby, it's cold outside. PMID- 24228286 TI - Fresh from the freezer: Pair frozen foods with pantry products to whip up quick and easy main dishes. PMID- 24228287 TI - Your heart-smart kitchen. PMID- 24228288 TI - Ready for action: rehab patients benefit from inclusive design. PMID- 24228295 TI - Final rules under the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008; technical amendment to external review for multi state plan program. Final rules. AB - This document contains final rule implementing the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008, which requires parity between mental health or substance use disorder benefits and medical/surgical benefits with respect to financial requirements and treatment limitations under group health plans and group and individual health insurance coverage. This document also contains a technical amendment relating to external review with respect to the multi-state plan program administered by the Office of Personnel Management. PMID- 24228297 TI - Abstracts of the 4th Central European Forum for Microbiology. October 16-18, 2013. Keszthely, Hungary. PMID- 24228296 TI - Abstracts of the Annual Meeting of the Hungarian Society for Microbiology. October 24-26, 2013. Keszthely, Hungary. PMID- 24228298 TI - Abstracts of the 67th Meeting of the Italian Society of Anatomy and Histology. September 20-22, 2013. Brescia, Italy. PMID- 24228299 TI - An interview with Won Moon. By Andre Wilson Machado, Barry Briss, Greg J Huang, Richard Kulbersh and Sergei Godeiro Fernandes Rabelo Caldas. PMID- 24228300 TI - Abstracts of the 66th Meeting of the Italian Society of Anatomy and Histology. September 20-22, 2012. Pistoia, Italy. PMID- 24228301 TI - [Dear colleagues , dear colleagues , dear friends]. PMID- 24228302 TI - The authors respond. PMID- 24228303 TI - AVMA governance changes. PMID- 24228304 TI - [Sleep disorders and work: guidelines for health surveillance, risk management and prevention]. AB - Sleep disorders and related diseases are becoming increasingly relevant for the health and wellbeing of the general and working populations. Sleep disorders affect all aspects of health, showing a bi-directionality with health conditions and comorbidity with several diseases. Consequently, sleep disorders may have severe negative consequences both for the individual and the enterprise, as well as for society on the whole, in terms of health, productivity and social costs. When considering the disturbances of the sleep/wake cycle, it is important to distinguish between those connected with endogenous biological factors from those related to socio-environmental conditions, including work, and those associated with mental and physical diseases, that are often associated and interact with each other. Many sleep disorders are still underestimated and under-valued in clinical practice and, to a much greater extent, in workers' health surveillance. The present paper is aimed at drawing the attention of the occupational health physician to some key issues, particularly regarding excessive daytime sleepiness, obstructive sleep apnea syndrome and shift and night work, as well as their implications in terms of health and occupational consequences. Information on the main aspects of clinical diagnosis and health surveillance, as well as risk management and prevention at the workplace, are provided. PMID- 24228305 TI - Estimating medical costs of work-related diseases in the Basque Country (2008). AB - OBJECTIVES: To estimate the medical costs of work-attributable diseases (WAD) treated by the public health care system for one of the Spanish Autonomous Communities, the Basque Country, in 2008. METHODS: We calculated the burden of disease attributable to work for each category of diseases according to ICD-9-CM by using estimates of attributable fractions. Hospital and specialized outpatient care cost data were derived from the Spanish National Health System analytical accountability system. Secondary sources of information were used to estimate primary health care and drug prescriptions. RESULTS: Direct costs of work attributable diseases borne by the Basque Regional Health Service totalled 106 million Euros in 2008, representing 3.3% of Basque public expenditures on health and 0.16% of Basque GDP in 2008. Specialized care, including hospitalizations, absorbed the highest proportion of costs (52%), followed by drug prescriptions and primary health care (27% and 21%, respectively). Diseases of the musculoskeletal system and connective tissues accounted for 47.3% of total costs, followed by cardiovascular diseases (19.6%) and cancer (15%). CONCLUSIONS: Occupational diseases and accidents are costly in the Basque Region of Spain, generating a severe deviation of public expenditures and overburdening of the Public Health System because they should really be the responsibility of the Social Security System. Proper identification and assignment of costs of work related diseases would result in significant savings for the National Health System (Spanish and European), would provide an incentive for the prevention of these avoidable causes of illness and thus contribute to the sustainability of social systems. PMID- 24228306 TI - [Asbestos-related diseases in former asbestos-cement workers in Senigallia]. AB - BACKGROUND: A factory that produced asbestos-cement products, using chrysotile, amosite and crocidolite in very low percentages, cement and water, operated in Senigallia from 1948 to 1984. Workers and residents still living in Senigallia are 238. OBJECTIVES: The need for an organic response to requests by former workers for protection of health and recognition of occupational diseases induced the Prevention and Safety at the Workplace Service in Senigallia/Area Vasta 2 to implement a programme of health surveillance. METHODS: In 2010 a health surveillance programme was initiated that involved 158 subjects, 58 women and 100 men. The average age of men was 75 years and 70 for women. The time elapsed between first exposure and participation in the programme was on average 50 years (SD 7.49). The average number of years of exposure to asbestos fibres was 17 (SD 10.36). The programme included counselling activities, especially as regards cessation of smoking, and first and second level health checks. RESULTS: The health surveillance programme enabled us to diagnose pleural plaques and pleural thickening in 81% of the subjects and various degrees of interstitial abnormalities in 49.4%. The high percentage of asbestos-related diseases was connected mainly with the long latency of the population under study and the higher diagnostic sensitivity of low dose chest CT scan applied to these diseases. CONCLUSIONS: In our experience, in order to optimize the benefits of a health surveillance programme of former workers exposed to asbestos, it will be advisable to define parameters of access to the programme for individual subjects in relation to life expectancy, clinical conditions, time elapsed since first exposure, time of cessation of exposure. Such parameters, together with any risk factors, will influence the diagnostic process. PMID- 24228307 TI - [Health education on occupational risks: a target not yet achieved? Workers' opinions collected via a questionnaire]. AB - INTRODUCTION: This study collected the opinions of sample of workers, sent to the Department of Occupational Medicine of Brescia Civil Hospital, on the contents and the methods used for carrying out information programs on the occupational risks in their workplaces. METHODS: A questionnaire including three sections has been prepared: in the first section demographic data and information on the job were collected, in the second section the contents of programs on the prevention of occupational risks were evaluated, the third section investigated how these programs have been performed. RESULTS: 250 workers have been examined; 16 self employed workers have been excluded. Mean length of employment was sixteen years. 29% of workers reported to have received information about the role of the main actors of the prevention in the workplaces according to the Italian legislation; overall 41.8% of workers have been informed both on occupational risks in their factory and specific job-related risks, potential occupational diseases and working procedures to prevent these risks. 7.2% of workers did not receive any information on occupational risks. 24% of subjects referred the involvement of the occupational physician in the information meetings. 55% of these meetings lasted more than 60 minutes and included frontal lectures and the delivery of information leaflets; learning assessment was referred by 50% of the workers and 77.9% considered the information (contents and quality) at least sufficient. DISCUSSION: This study, even if preliminary and based on anamnestic data, pointed out that, at this moment, careful information on occupational risks in the workplaces seems a target not yet achieved. It is desirable to verify in the future the improvement of the quality of information given to workers, following the entry into force of the recent Italian legislation concerning this topic. PMID- 24228308 TI - ["On professions considered as a cause of disease" (1849) by Enrico de Betta. The first Italian modern discussion on diseases and work]. AB - The doctoral dissertation in Pavia in 1849 by Enrico de Betta is presented as a well-constructed, comprehensive and modern discussion of diseases ascribable to work. 150 years after Ramazzini's treatise, Enrico de Betta, through an updated knowledge of contemporary literature especially French and German, refreshed and renewed the knowledge inherited from Ramazzini in the light of the changes introduced with the beginnings of industrial hygiene and the first steps taken in occupational epidemiology. In the introduction to the text and accompanying notes, the authors offer an interpretation of the significance of overcoming the main Ramazzinian paradigms. This takes into account the current debate, especially in the French cultural sphere, on the meaning of autonomy and complementarity of the various disciplines that are the foundations of the protection and promotion of the health conditions of the working classes. It is suggested therefore that a simplistic view of Ramazzini as the unique 'father" of modern occupational health and safety at work needs to be abandoned. The work of de Betta does not seem to have had much success in Italy. The debate and interventions on the relationship between diseases and work still had to wait half a century to produce effects, but this took place in a very different context, that of Giolitti's era. PMID- 24228309 TI - [Protection of working mothers: operational guide document. The Marche Regional Section of the Italian Society of Occupational Health and Industrial Hygiene (SIMLII) ]. AB - Protection of working mothers: operational guide document. The aim of this operational guide document is to protect the health of working mothers and their babies during pregnancy, puerperium and breastfeeding. The project was developed by a technical working group which included professionals in the pertinent fields from the Workplace Prevention and Safety Services of the local Vasta-2 Area of the Marche Regional Health Service:physicians, health assistants, and nurses. It is considered to be a useful tool for risk assessment at the workplace aimed at professionals who are involved, with various duties and responsibilities, in the health care of the working mother. This paper consists of two functionally related sections, "Table of risks" and "Technical specifications". In the "Table of Risks" section, the occupational hazards for women during pregnancy or postpartum were analyzed with the highest possible degree of care. To this end the technical group provided, for each occupational hazard, its own operational suggestions, in relation to legislation, current scientific knowledge and Guidelines of other Italian Regions. The Marche Regional Section of the Italian Society of Occupational Health and Industrial Hygiene (SIMLII) participated in the final draft of the entire document. The second section, "Technical Specifications", illustrates the main tasks and any risks involved in the 34 manufacturing sectors most prevalent in this area. This operational guide document is intended to be the beginning of a common strategy in public health to achieve a wider field of action in promotion and information aimed at protecting the reproductive health of working mothers. PMID- 24228310 TI - [The new role of the physician-in-charge in the business organization system]. PMID- 24228311 TI - Protecting number one. PMID- 24228312 TI - Medicaid update. PMID- 24228313 TI - LSUSD Oral and Maxillofacial Surgery Program embraces change. PMID- 24228314 TI - Making the profession better & fulfilling our mission. PMID- 24228315 TI - How to turn patients into raving fans. PMID- 24228316 TI - 2013 marks 100th anniversary of dental hygiene profession. PMID- 24228317 TI - Infection control education integral to dental assistant training. PMID- 24228318 TI - Financial planning for special needs children. PMID- 24228319 TI - The importance of education in dental assisting. PMID- 24228321 TI - From idea to innovation: A dental assistant's journey through the patent process. PMID- 24228320 TI - Navigating online networks: Making social media work for the dental team. PMID- 24228322 TI - Air Force dental personnel improving their communities. PMID- 24228323 TI - The role of the dental assistant in embracing whitening. PMID- 24228324 TI - Expanding outreach in the dental community. PMID- 24228325 TI - [Bet on the talent of our team]. PMID- 24228326 TI - [We need to make careers in early childhood attractive for men]. PMID- 24228327 TI - [Detecting and fighting rare diseases. A necessary expertise]. PMID- 24228328 TI - [Rare diseases, definitions and epidemiology]. AB - There are between 6 000 to 8 000 rare diseases, of which 80% are of genetic origin. Most of them appear very early in life. Patients and their families are faced with diagnostic delays, inadequate management as well as a lack of information and resources.A large number of these pathologies are also sometimes called orphan diseases because the populations concerned do not find any treatments. PMID- 24228330 TI - [Prader-Willi syndrome]. AB - Prader-Willi syndrome is a rare genetic disease that affects neurodevelopment in children. It is characterised by major behavioural problems and morbid obesity. Early diagnosis and growth hormone treatment can bring out considerable improvements. However, the outlook for adults remains problematic. PMID- 24228329 TI - [Rare diseases, a public health issue]. AB - Under the influence of patients' associations, rare diseases have gradually become recognised as a public health issue. A first Rare Diseases National Plan, from 2005-2008, endeavoured to facilitate diagnosis and access to care. A second Plan, for 2011-2014, aims to improve patient management and develop research and international cooperation. The Rare Diseases Platform provides an essential resource for families and professionals. PMID- 24228331 TI - [Support for patients and families living with a developmental disability]. PMID- 24228332 TI - [Education on caring for children with inherited epidermolysis bullosa]. AB - Inherited epidermolysis bullosa is a rare dermatological disease that requires specific daily care. An education programme teaches parents how to bathe their children in optimal conditions described in a care protocol that encourages contact and promotes the parent-child relationship. PMID- 24228333 TI - [A multiprofessional team for children living with sickle-cell anemia]. AB - Sickle-cell anaemia is a rare hereditary disease characterised by abnormal blood cells. It causes highly painful vaso-occlusive crises. Multi-professional care is encouraged through the intervention of a network. PMID- 24228334 TI - [Pierre Robin syndrome and support from associations]. AB - Pierre Robin syndrome is a combination of three face and mouth malformations that affect nutrition, teething, language and sometimes breathing. In a context where information is lacking about this rare disease that affects one in 10,000 children, associations can facilitate access to specialised teams while providing families with helpful support and advice. PMID- 24228335 TI - [Bibliography. Detecting and fighting rare diseases]. PMID- 24228336 TI - [Pain relief for children in cultural contexts]. AB - Around the world, pain relief for children still remains a sensitive issue influenced by beliefs and taboos. Perceptions of pain and pain tolerance depend on many factors. Nurses prevent and relieve children's pain while taking into account each family's cultural issues. PMID- 24228338 TI - [Intuition in pediatric care]. AB - Caregiver intuition acquired through experience can be considered a form of intelligence in action. It is used in both reflection and field learning and can be mobilised as part of any nurse's clinical context. Transferring knowledge to young professionals should therefore include intuition to help them adapt to each care situation, especially in paediatrics. PMID- 24228337 TI - [Cross-cultural consultations, a forum for adolescent trauma victims]. AB - Cross-cultural consultations for adolescents are part of the creative, multi disciplinary approach that their complex clinical context requires. For youth who have suffered a traumatic event, this psychotherapeutic work is restorative and reassuring. It provides support required to stimulate the mental processes of often stunned youth in psychological distress who have been isolated from their families and cultures. PMID- 24228339 TI - Health care innovation in the Asian Tigers and their cubs. Editorial. PMID- 24228340 TI - Process reengineering of preoperative verification, site marking and time-out for patient safety. AB - In this article, we describe our hospital's journey in implementing the WHO High 5s Project Correct Site Surgery Standard (CSS) protocol. We discuss how we incorporated the protocol into our system by revising the pre-existing checklist, reengineering the existing processes on preoperative verification, site marking and time-out at the Major Operating Theatre (MOT), and performing audit and feedback to ensure effective compliance. We also reflect on the importance of leadership and ministry support, benchmarking and tailoring the practice for each discipline in the pursuit of improving patient safety within the hospital. PMID- 24228341 TI - A census study exploring the training needs of nurses working in Kwong Wah Hospital and Wong Tai Sin Hospital in Hong Kong, China. AB - As part of the strategic professional development plan for nurses, training needs analysis was conducted from August 2011 to February 2012, in the form of descriptive research with survey design. The aim was to support nursing staff in their professional development needs and promote staff engagement. Consecutive sampling was employed; all full time nurses working in Kwong Wah Hospital (KWH) and Wong Tai Sin Hospital (WTSH) were recruited and invited to complete a self administered questionnaire. Based on the findings and conclusions, follow up strategies were proposed. Management then built a sustainable learning environment for KWH and WTSH nurses in the 2012-2015 professional development plan. PMID- 24228342 TI - Increasing productivity by reducing average length of stay (ALOS) in Apollo Gleneagles Hospitals, Kolkata, India. AB - Reduction of ALOS in the hospital through streamlined processes with validation for standardized work such as clinical pathways. The implementation of barcoding and streamlining laboratories with interface solutions has reduced the cycle time for the diagnostic areas. The long standing cases over seven days provided a trigger for the Medical Board, which helped in multidisciplinary care of these patients. Cohort of patients in respective wards according to discipline for almost 80% of patients have improved nursing and other paramedical services and had a definite impact on ALOS and other outcomes. Finally, the organization had a benefit of nearly USD 0.9 million for a period of nine months during this study. The organization has carried on with the benefits of the ALOS reduction and currently has reduced ALOS to 4.5 days. PMID- 24228343 TI - The Antimicrobal Stewardship Programme: where have we been...where are we going? AB - The misuse or overuse of antibiotics has been widely documented as one of the major causes of the emergence and transmission of multi-drug resistant organisms (MDRO). Antimicrobial resistance posed significant impacts to the increase in morbidity, mortality and cost of health care. In response to the threat of antibiotic resistance which has increased dramatically over the past ten years and the very few new antibiotics in the pipeline, Princess Margaret Hospital set up a Steering Committee with senior-level representatives from Infectious Disease, Microbiology and Pharmacy departments to devise an interventional programme called the Smart Use of Antibiotics Programme (SMAP) to offer guidance on the judicious use of antimicrobials. With concerted effort and support from hospital management and frontline clinicians, SMAP achieved significant monetary savings and a reduction in inappropriate antibiotic use. There was no adverse patient outcome in terms of mortality and morbidity PMID- 24228344 TI - Voice of the customer---a roadmap for service improvement. AB - Patient satisfaction surveys help a great deal in identifying ways of improving a hospital's services. Ultimately, that translates into better care and happier patients. Moreover, it shows the staff and the community that the hospital is serious about quality and is looking for ways to improve. This article describes how the Voice of the Customer (VOC) Survey can be used as a tool for improving services. Regular monitoring of VOC scores is essential for minimizing the gaps between service delivery and patient expectations. The present study showcases the various initiatives undertaken to improve the VOC scores from an original 4.40 to 4.77 (on a 5 point scale) at the hospital under study. PMID- 24228345 TI - A study of patient satisfaction at a tertiary care hospital in Hyderabad, India. AB - The health care industry is fast changing and rapid transformation is required to meet the ever-increasing needs and demands of its patient population. Hospitals and health care providers are shifting from viewing patients as uneducated with few health care choices to educated consumers with many service demands and health care choices available. Modern health care organizations have identified the patient as an ultimate consumer of hospital services and understand the importance of patient satisfaction, establishing this as the yardstick. The present study is explorative in nature. This cross sectional study is aimed at collecting data regarding attitude of patients, assessing their satisfaction levels towards ease of getting care, facilities offered at the hospital, attitude of the staff at the hospital and overall status of the hospital. The research study revealed many insights regarding attributes that are important for doctors, nurses and hospitals which would match patient expectation and lead to satisfaction. PMID- 24228346 TI - The tele-interpreter service at the Bangkok Hospital Medical Center, Thailand. AB - Thailand has become one of the most famous medical hub countries, which is reflected in the increasing number of international patients visiting the Bangkok Hospital Medical Center (BMC). In response, the Interpreter Department at BMC has been established to provide translation for non-English speaking patients. Overtime the Interpreter Department frequently reaches maximum capacity when providing prompt services on demand, resulting in long waiting times and delayed medical treatment. BMC has foreseen the necessity to implement a tele-interpreter system via videoconferencing technology to provide effective translations in the medical environment where delay is usually not tolerated. Tele-interpretation allows doctors to simply select a language icon on their Wi-Fi IP telephone to instantly connect to an interpreter. After implementation in 2oo9, the overall customer satisfaction index for the Interpreter Department increased from 64.5% in Quarter 1 to 85.5% in Quarter 3 of 2011. The tele-interpretation system is currently the closest approximation to the face-to-face interpretation method. PMID- 24228347 TI - Financing health care in the United Arab Emirates. AB - Newcomers to the United Arab Emirates (UAE) health care system often enquire about the way in which UAE health services are financed particularly when funding issues affect eligibility for treatment. The UAE ranks alongside many western counties on measures of life expectancy and child mortality but because of the unique population structure spends less of its national income on health. In the past as a wealthy country the UAE had no difficulty ensuring universal access to a comprehensive range of services but the health needs of the UAE population are becoming more complex and like many countries the UAE health system is facing the twin challenges of quality and cost. To meet these challenges new models of health care financing are being introduced. In this brief article we will describe the evolution of UAE health financing, its current state and likely future developments. PMID- 24228348 TI - Parsley, sage, rosemary and foxglove. PMID- 24228349 TI - Presidential profile: Omar Atiq, MD: The bold journey of a passionate physician. PMID- 24228350 TI - Arkansas Payment Initiative. PMID- 24228351 TI - Mosquito-borne infections: diagnosis and treatment. PMID- 24228352 TI - CME: Arkansas Prescription Drug Monitoring Program: informing physicians how to use new monitoring tool. PMID- 24228353 TI - [Laparoscopic adrenalectomy for neuroblastoma. Our serie and review of literature]. AB - INTRODUCTION: Neuroblastoma is the most frequent adrenal mass in paediatric patients. Paediatric series about laparoscopic adrenalectomy are scarce, usually including adrenal masses from different origin. Series referring only to neuroblastoma are very rare. MATERIAL AND METHOD: We present 7 patients between 4 and 48 month of age. RESULTS: We performed 8 laparoscopic adrenalectomy and one biopsy. Lateral transperitoneal approach was used in all patients. We employed 3 ports on the left side and 4 on the right side. All tumours were extracted into a bag through the most posterior incision. One patient underwent a laparotomy because of important adherences. The average operative time was 88 minutes, and average time before discharging was 48 hours. CONCLUSIONS: Laparoscopic adrenalectomy is the gold standard in adult patients. Transperitoneal access achieves better working area. Paediatric patients don't have many surgical indications for adrenalectomy and the space inside the patient's body is smaller. Laparoscopy offers a less painful solution than open surgery, so that sooner discharging, and better scar's results. The outcome is similar to traditional surgery. Laparoscopy is an useful and safe procedure in paediatric patients with adrenal neuroblastoma, in very selected cases. PMID- 24228354 TI - [Analysis of efficacy in diaphragmatic plication with minimally invasive surgery]. AB - OBJECTIVE: Diaphragmatic paralysis may result difficulty for respiratory compromise and extubation. We study the effectiveness of diaphragmatic plication held in its two modalities: videothoracoscopy assisted surgery (VATS) and percutaneous with needle. MATERIAL AND METHODS: Retrospective study of diaphragmatic plication performed in our center in the past three years. Review of clinical histories, analyzing the variables: sex and age, etiology and laterality, surgical indications, technique, ventilation support, complications and outcome. Data Analysis with SPSS 18.0. RESULTS: From 2009-2012, 24 diaphragmatic plication were realized (7 left, 13 right, 2 bilateral) in 22 children (15 males). The mean age was 10.4 months (2 to 23.1). In 68.1% paralysis was secondary to thoracic surgery. In 12 patients was performed VATS and in 5 percutaneous with needle. Surgical indications were: respiratory distress (69.1%) with intercurrent processes (pneumonia, bronchiolitis, and atelectasis) and failure of extubation in 27.3%. After diaphragmatic plication in 90.9% respiratory symptoms remitted. Extubation was accomplished in all patients, requiring ventilator support for 12-96 hours. Mean hospital stay was 7.5 days (3 to 13.5). There were no complications derived from surgery. There were two recurrences (9.2%) and only one was reoperated (4.6%). The percutaneous technique decreased the required postoperative analgesia and improved cosmetic outcome in 90.9%. CONCLUSIONS: The diaphragmatic plication by minimally invasive surgery reduces operative morbidity and facilitates extubation of ventilator-dependent patients with diaphragmatic paralysis. The percutaneous technique improves the cosmetic results and reduces pain after surgery, without finding differences with VATS. PMID- 24228355 TI - [Implementation of "fast-track" treatment in paediatric complicated appendicitis]. AB - OBJECTIVE: Acute appendicitis is the most common emergency surgical pathology in childhood and there is no consensus on its management. Fast-track treatment, based on optimizing perioperative care has reduced morbidity and mortality of surgical pathologies, including simple acute appendicitis. The aim of our study was to assess the effects of a fast-track protocol in complicated acute appendicitis. METHODS: Ambispective cohort study. Historical unexposed cohort: children with complicated appendicitis and appendectomy in our hospital during 2008-2009. Exposed cohort: children operated in 2010-2011 and who performed protocol. The protocol treatment was done after a literature review, adapting the principles of fast-track to a potentially severe urgent disease: early mobilization, limited drainage-tubes and short antibiotic regimens Taking hospital stay as the resulting variable, the calculated sample size for alpha = 0.05 and power = 90% was 54, being X1 = 7 +/- 3DS and X2=5. RESULTS: We included 151 patients, historical cohort 81 and current cohort 70, which excluded 31 children who did not meet protocol because of surgeon choice. Both groups showed homogeneity due to the absence of differences in sex, age, weight, type of appendicitis (gangrenous, perforated, generalized peritonitis) or surgical approach. The average stay decreased 2.71 days (p <0.001) due to the protocol, without any complication increase (abscess, postoperative ileus, readmission). CONCLUSIONS: Complicated appendicitis in children is common and potentially serious, and optimization of treatment should be a primary goal of our practice. Application of a fast-track protocol can provide clinical and economic benefits, although this requires an appropriate multidisciplinary management. PMID- 24228356 TI - [Long gap esophageal atresia: Scharli versus Foker]. AB - PURPOSE. To submit the short and long term results of long-gap esophageal atresia (EA) with two surgical techniques. METHODS. We carried out a retrospective study of long-gap type EA without fistula (n=8) and with fistula (n=2) over the last 18 years, comparing the outcome of the Scharli technique (1992) with that of the Foker technique (1997). RESULTS. We included 10 patients with long gap EA. Mean birth weight was 2,418 grams. 30% had associated diseases (VACTERL, Down Syndrome, DiGeorge Syndrome). Gastrostomy or jejunostomy was initially placed in 7 patients. Scharli technique was performed in 4 patients (mean age: 3.3 months), and Foker technique in 6 patients (median age: 23.5 days of life). Complications were: a) Scharli: dehiscence (25%), stenosis (75%), one patient died from his heart disease (25%), colonic herniation through diaphragmatic hiatus (25%). The mean number of stricture dilatations was 7 sessions (S.D. 9.2). a) Foker: dehiscence (83.3%), stenosis (83.3%), gastroesophageal reflux (GER) (83.3%), fistula (16.7%). Mean number of dilatations was 13.7 sessions (S.D. 12.8). All patients operated on with Scharli technique (6-18 years, median follow-up 12 years) were asymptomatic at the time of the study, although one of them had grade III esophagitis in the last biopsy. As for the Foker's, 5 had undergone antireflux surgery and only one was asymptomatic. The rest had complications that were still being treated (stenosis and development of fistulae). CONCLUSION. Treatment of long gap EA remains a surgical challenge. In our experience patients developed fewer complications with the Scharli technique. Nevertheless, it is difficult to make a comparison with such a limited number of patients. PMID- 24228357 TI - [Role of pediatric urologist in the treatment of congenital adrenal hyperplasia: a study of satisfaction and psychosocial aspects]. AB - OBJECTIVE: Study the role of the pediatric urologist in the treatment of CAH and the satisfaction of families and patients to identify the psychosocial aspects that we can improve. MATERIAL AND METHODS: Retrospective study in girls with CAH treated in our center. We reviewed the medical records, analyzing the variables: place of birth, age at diagnosis, surgery, complications and follow up. Analysis of satisfaction and psychosocial aspects by telephone survey. RESULTS: Between 1975-2011, 25 girls with CAH have been treated in our center. Cystoscopy and vaginoscopy was performed before clitoroplasty in 68% (16 girls), adding vulvovaginoplasty in 40% and vaginal descent in the 20%. The mean age was 8.78 +/ 2.30 months. Vaginal stenosis was the main complication (36%), performing introitus plasty in two girls, vaginal expansion in other 2 and dilation of the rest. 15 surveys were made, all expressed satisfaction with treatment, and only 6.67% reported shortages information. With the aesthetic results of the genitoplasty 20% showed dissatisfaction. The family concern was constant at 60%, and sporadic in the rest. 13.3% required psychological support. Currently 80% have normal psychosocial life. CONCLUSION: The HSC requires a multidisciplinary approach right from birth to allow adequate psychosocial development. The pediatric urologist has an important weight in the multidisciplinary treatment. Realizing early feminizing genitoplasty decreases family impact and increases satisfaction. The prolonged follow-up will allow the detection and treatment of complications. PMID- 24228358 TI - ["Fast-track" in pediatric urologic surgery: pronenephrectomy]. AB - INTRODUCTION AND OBJETIVES: Minimal invasive surgery trends to get prompt recovery in terms of inmediate deambulation and early discharge from hospital, without increasing patient's discomfort neither postoperative complications. This "fast-track" protocol is being progresively introduced in a crescent number of urological procedures. We are evaluating the viability of applying it in retroperitoneoscopic prone- position nephrectomy. METHODS AND MATERIALS: We have performed a retrospective review of the clinical reports of the patients submitted to prone nephrectomy with hospitalization between 2007 and 2011 and we present patients submitted to this procedure in an outpatient basis (less than 8 hours hospital stay) from 2011. We have recorded epidemiological factors, diagnosis, surgical time, first postoperative week analgesic requirements, parents cofort and postoperative complications. RESULTS: All the procedures were performed retroperitoneoscopically in prone position using two trocars. We included 34 nephrectomies with a mean surgical time of 107 minutes. Mean postoperative stay was under 24 hours in 23 patients, two of them were discharged in the first 8 hours after the procedure. Hospital stay over this time was due to concomitant pre-existent pathology in 6 patients and to non urological fever in the remaining 3. Analgesia was excellent in every patient with endovenous non steroid drugs, registering no pain after administering them orally. There were no complications. CONCLUSIONS: We believe that "fast-track" requirements can be applied to prone-retroperitoneoscopic nephrectomy in pediatric population, as long as they have no associated pathology. In our experience this surgical procedure can be included in day-case surgery, increasing patient's confort and with a positive economical impact. PMID- 24228359 TI - [What can we do to improve our management of intestinal atresia?]. AB - OBJECTIVE: To review our management of intestinal atresia (AI). MATERIAL AND METHODS: A retrospective review of patientes with AI, from 1995 to 2011. RESULTS: AI was identified in 41 patients, 29,2% had maternal polyhydramnios and 48,7% were diagnosed prenatally. Four of them had Down Syndrome and 18 had cardiopathy. Duodenal atresia-stenosis (AD) was present in 21 patients, that were treated by 19 duodenoduodenostomy, 1 duodenojejunostomy and 1 duodenotomy with duodenal membrane resection. Jejunoileal atresia (AYI) was present in 20 patients and we performed 15 end to end anastomosis, 1 ileo-colic anastomosis, 1 ileostomy, 2 jejunostomies and 1 end to end anastomosis with jejunostomy. Nine AYI were reoperated: 6 bowel obstructions, 1 evisceration and 2 colo-rectal atresia. The average time on parenteral nutrition was 29 days and average hospital stay was 37,3 days. One AD died due to heart disease. In AYI, 2 required transfer to another center due to short bowel. CONCLUSIONS: Prenatal diagnosis of AI is difficult, especially AYI, which is only prenatally diagnosed in 35% of cases. AD respond better to surgery and rarely require reoperation, but mortality is higher than AYI because 57% suffer from heart disease. Reoperations are frecuent in AYI (45% of our patients), usually due to obstruction, ostomy closure and problems resulting from extensive bowel resections. It's important to keep in mind colorectal atresias, which can not be identified. PMID- 24228360 TI - [Biodegradable catheters for fistula prevention in hypospadias. Experimental preliminary study]. AB - INTRODUCTION: Continuous technical innovations are not enough to resolve the high incidence of fistula after hypospadias repair. A urethral catheter-tutor made of reabsorbable polymeric biomaterial (RPB) which could be left in situ long enough could reduce the complications. TARGET: To investigate in an animal model differents RPB to be used in urology. METHODOLOGY: CRL Wistar rats, males, divided into 5 equal groups according to the used polymers: polylactide; lactic coprolactone copolymer; lactic-glycolic copolymer; simulated; control silicones. Three individuals were sacrificed per group at 4th, 10th and 16th week. In all animals (exceptuating the simulated group), biomaterial was fixed to the bladder wall bylaparotomy. Animals remained in individual housing and kept under daily control of hematuria during the first 15 days and weekly weight and urine control for pH and lactate. After being slaughtered, remaining polymer was collected for chemical analysis and bladder tissue for hystologic study. RESULTS: There was no mortality, hematuria nor other clinical signs. The bladder wall showed a mild foreign body reaction. The values of lactate and pH in urine did not reach toxic levels. Lactic-glycolic was totally reabsorbed by the 10th week and had the lowest degree of calcification. Polylactide and lactic-coprolactone remained intact. CONCLUSION: The model of urinary bladder has proven useful for studying the degradation of bioresorbable polymers. The analyzed polymers have spent long time to be reabsorbed, so we will have to study new others. PMID- 24228361 TI - [Thoracoscopic treatment of secondary pneumothorax to costal osteochondroma]. AB - Costal osteochondromas are benign, uncommon and usually asymptomatic tumors, but may be associated with severe intrathoracic complications such as pneumothorax, hemothorax, nerve or vascular injury and fractures. We report a 12 year old patient, who presented a right spontaneous pneumothorax, which did not improve with standard treatment. Thoracic CT showed a costal exostosis of 2.5 cm in length. Excision was performed by videothoracoscopy (VATS), with good postoperative course. We consider the thoracoscopic approach as the most appropriate initial way in this type of tumors. PMID- 24228362 TI - [Testicular cancer and cryptorchidism: myth or reality]. AB - OBJECTIVE: To evaluate the previous history of cryptorchidism in patients with testicular cancer. MATERIALS AND METHODS: We carried out a study using 175 patients diagnosed with testicular cancer, in our hospital, from 1999 to 2010. We analyzed the previous history of cryptorchidism and its characteristics, testicular placing, histology and intervention age. RESULTS: 5 out of the 175 patients (2,8%) with testicular neoplasm presented a history of cryptorchidism, The average age was 31 years old, an orchidopexy was only carried out in 2 patients. The histology was different depending on the treatment chosen to battle cryptorchidism and in 2 cases it developed in the adjoining testicle. The average ratio was of 1,9. CONCLUSIONS: Our results reflect that the association of cryptorchidism with testicular neoplasm is in fact lower than in the past. A good and proper handling of cryptorchidism can prevent it from turning malignant, presenting these patients similar incidences to the rest of the population. PMID- 24228363 TI - Scramble to implement healthcare reform continues as October 1 deadline nears. PMID- 24228364 TI - Office-based surgery: embracing patient safety strategies. AB - Office-based surgery continues to grow as more procedures are being performed in the outpatient setting. With this exponential growth, there is an increasing emphasis on safe and effective patient care. Current research shows both gaps in safety and opportunities for improvement. Practice managers, clinicians, and other personnel should be cognizant that office procedures are coming under intense regulatory scrutiny. Effective strategies to maintain quality and patient safety include the use of checklists, obtaining office accreditation, encouraging board-certification and proper credentialing of proceduralists, and appropriate patient and procedure selection. There is increasing regulation of ambulatory surgery on state and national levels that will likely affect the financial and care quality aspects of office-based practice. Socioeconomic and political forces will continue to shape the future of office-based surgery. PMID- 24228365 TI - Purchasing technology: a few things to consider. AB - Standard-form software and hardware contracts need critical review to ensure that the product meets the needs of the practice. PMID- 24228366 TI - Online reputation management: the first steps. AB - Can patients reliably choose a good doctor online? Inevitably, some will. Many doctors are not comfortable being visible online. So if you do not have a blog or a social media profile, what shows up when a patient Googles you most likely will be something from an online rating site. This trend can have a profound impact on a medical practice. As one of authors (KP) noticed, patients are now saying that they found his practice through the Internet, in stark contrast to 10 years ago, when their information sources were the Yellow Pages or a newspaper ad, or from calling the local hospital. Below are five key reasons why determining your online reputation today can pay off in the future. This article will guide you in establishing your social media footprint and includes a personal story of one physician's reaction to conducting a Google search on herself. PMID- 24228367 TI - Understanding awareness of pharmacist-led medication therapy management among primary care physicians in New York City using qualitative methods: part I. AB - Pharmacist-led medication therapy management (MTM) programs have been shown to be an effective method of optimizing patient therapy for multiple disease states through improved clinical outcomes and decreased healthcare costs. Physicians have recognized pharmacists' ability to identify and prevent prescription errors, and educate patients about safe and appropriate medication use. Pharmacist interventions may help ease the burden of chronic disease among primary care providers and pave the way for a team-based approach in caring for underserved patients with heavy disease burdens. The New York City Department of Health and Mental Hygiene performed a qualitative study to obtain a better understanding of the perceptions related to pharmacist-led MTM programs among primary care physicians in New York City. Key findings from our study suggest that educating physicians on MTM and the role of pharmacists in the healthcare team is crucial to building trusting relationships for collaborative patient care. Key concerns among physicians included demonstrated pharmacist competency, integration of documentation systems, impact on workload, and effective collaboration between physicians and pharmacists. In this article, we describe our study rationale, design, and preliminary findings. A more detailed report and potential impact of our findings will be provided in Part II of this article. PMID- 24228368 TI - Partnerships in medical business: a framework for choosing the right key players. AB - At a time when more and more physicians are opting for shared practices and embarking on business ventures, partnerships play a key role. The fate of a medical business is largely contingent upon the success of the partnership. In this article, the author introduces a practical framework for deciding whether to take on a partnership. The model considers six critical factors: financial compensation, special skill set, goal alignment, personality assessment, overall strengths and weaknesses, and trustworthiness. It also provides an evaluation of financial incentives. The paper also provides several action items for physicians. PMID- 24228369 TI - You've been served! AB - Regardless of how difficult this process may be, you want the plaintiff's attorney to believe that you are a formidable opponent. You want the attorney to know that you will give the jury an impression of a competent, caring physician who practiced within the standard of care and did everything possible to provide appropriate care for the patient. Smart attorneys will factor this into the chances of winning a verdict, and following a strong physician performance in a deposition, will often drop the case. With all things being equal, jurors frequently side with the litigant who is seen as more credible. Pay close attention throughout the deposition. Pause slightly at the beginning of every answer to make sure you understand the question and to give your attorney time to object if need be. PMID- 24228370 TI - Patient loyalty and the social media effect. AB - In a changing healthcare environment, patient loyalty has never been more important. However, creating patient loyalty can mean more than providing quality health services within the four walls of the medical office. With patients turning to online sources and social media in search of advice and a better patient experience, we must now ensure that patients have meaningful engagements with us across the continuum of care, from the phone, to the office, to social media tools like Facebook and YouTube as we look to build loyalty and grow our referral volumes. PMID- 24228371 TI - Overcoming the ten most common barriers to effective team communication. AB - Communication is at the heart of medical practice management. Yet there are many barriers to effective communication that can interfere with the smooth running of the practice. This article describes the 10 most common barriers to effective medical practice team communication and offers six steps the practice manager can take to break them down. This article also suggests that the practice develop a team communication strategy. It suggests 10 communication principles readers can share directly with their teams and describes three hallmarks of effective team communication. Finally, this article provides a list of 25 practical questions practice managers can use to improve their team's communication. PMID- 24228372 TI - The seven elements of a payable claim. AB - Healthcare providers are obligated to comply with a wide range of statutory and regulatory requirements associated with the provision, documentation, coding, and billing of a medical claim. It is important to keep in mind that the viewpoint of an outside auditor is not going to be the same as that of the treating physician. For instance, when documenting medical services, the information viewed as most significant (and therefore recorded) by a treating physician may be very different from the information an outside auditor hopes to glean from a patient's record. As a result, a significant disconnect between the parties may occur. To avoid this, it is essential that a treating physician or other healthcare provider diligently work to help ensure that claims submitted to Medicare, Medicaid, or a private payer fully comply with all applicable coverage and payment requirements. We have developed a checklist that we refer to as "The Seven Elements of a Payable Claim" to assist providers in this effort. PMID- 24228373 TI - Vision problems? PMID- 24228374 TI - Is your glass half full or half empty? Your decision may impact your practice. AB - The attitude of the doctor and the medical staff can have a profound impact on the success of a practice. You can be sure that if everyone has a positive attitude toward patients, your patients will have a positive experience and will tell others about that positive experience. On the other hand, if a doctor is sullen, unhappy, and uninterested in his or her work, you can be sure that this negativity will be transferred to the staff and subsequently to the patients. As a result, there will be unhappy patients, unhappy staff, increased staff turnover, and a doctor who continues to be unhappy and dissatisfied with the practice of medicine. This article will describe both types of attitudes, and what can be done to improve the attitude of the practice and have a glass that is half full and not half empty. PMID- 24228375 TI - Ten practice redesign approaches. AB - As healthcare delivery continues to evolve at a rapid pace, practices need to consider redesign approaches to stay ahead of the pack. From national policy and private payer initiatives to societal macro trends and the growing use of mobile technologies, delivering value, understanding customer needs, and assessing satisfaction are important elements to achieve and maintain success. This article discusses 10 practice redesign approaches. PMID- 24228376 TI - It was just a joke: improper comments and practice liability. AB - There can be a fine line between humor and harassment, and that line is now frequently explored in litigation. A racial, sexual, or ethnic joke or bullying comment is not nearly as funny in the courtroom as it was in the break room. In addition, a practice's owner or partner can be utterly undefendable. This article casts light on crucial issues of workplace humor, banter, and liability. PMID- 24228377 TI - Sustainability in medicine. AB - Given the current state of the U.S. healthcare system, with increasingly complicated regulations and paperwork and decreasing reimbursements, the question arises: Is it possible to provide safe, high-quality healthcare and reduce costs? Furthermore, is it possible to care for the health of your patients while simultaneously caring for the financial health of your practice and promoting improvement in the overall health of the planet? This article will review some steps currently being taken by various companies and hopefully stimulate ideas for changes you may want to consider for your own practice, hospital, or institution. PMID- 24228378 TI - Relationship building blocks and the new era of healthcare. PMID- 24228379 TI - Virtual medical scribes: making electronic medical records work for you. AB - There is increasing buzz around the term "medical scribe" in healthcare today. Medical scribes help meet the growing electronic medical record (EMR) data entry challenge healthcare providers face. Medical scribes reduce providers' paperwork burden, increase a medical practice's net margins, and reduce stress levels for doctors and their staff. They do this by charting patient encounters in real-time during patient examinations, thus reducing significantly the data entry workload that EMRs place on providers. Medical scribes can work onsite or offsite from a HIPAA-secure location, the latter being known as "virtual medical scribes." This article explores the uses and benefits of scribes to give you the background to employ them effectively in your clinic or hospital. PMID- 24228380 TI - Thinking like Leonardo da Vinci and its implications for the modern doctor. AB - Most people when asked to name the most creative, innovative, and multidimensional people in history would agree that Leonardo da Vinci is either at the top or very close to the number one position on that list. Wouldn't it be nice to think like da Vinci? This article shares the seven unique principles of thinking that da Vinci used that enabled him to be the greatest painter, sculptor, architect, musician, mathematician, engineer, inventor, anatomist, geologist, cartographer, botanist, and writer of his (if not of all) time. This article will take you deep into the notebooks and codices of da Vinci, and suggest ways his ideas can be used by anyone in the healthcare profession to make them a better healthcare provider. PMID- 24228381 TI - Computer briefs: the healthcare trifecta. PMID- 24228382 TI - Actinobacteriological research in India. AB - Actinobacteria are important sources of compounds for drug discovery and have attracted considerable pharmaceutical, chemical, agricultural and industrial interests. Actinobacteriological research is still in its infancy in India. Early work on actinobacteria started in the 20th century and mostly focused on studying the diversity, identification and screening for antibiotics, enzymes and enzyme inhibitors. Exploration of diverse habitats for the isolation of actinobacteria, have yielded till date 23 novel species. Screening of actinobacteria for antagonistic activity, has led to the discovery of four novel antibiotics. Research on enzymes mostly covered lipases, amylases, proteases, endoglucanases, a-galactosidases, pectin lyases, xylanases, L-asparaginases, L-glutaminase and cellulases. Research on exploiting actinobacteria for other purposes such as production of enzyme inhibitors, single cell protein, bioemulsifier and biosurfactants is still in the experimental stage. This review compiles the work done in last few years, with an emphasis on actinobacterial diversity and bioprospecting for pharmaceutically important compounds like antibiotics, enzymes and other important applications. The chemical creativity and biotechnological potential of Indian actinobacterial strains are yet to be fully explored. A national strategy is required consistent with the opportunities provided by CBD Nagoya protocol. PMID- 24228383 TI - Cytotoxic function of gamma delta (gamma/delta) T cells against pamidronate treated cervical cancer cells. AB - The cytotoxic function of polyclonal expanded gamma/delta T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The gamma/delta T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 microM pamidronate. The expansion of gamma/delta T cells was 15 times more than the non-stimulated cells. Among the expanded gamma/delta T cells, 47% were Vgamma9/Vdelta2 T cells with a purity of 87%. Analyzing the cytotoxic function of gamma/delta T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on gamma/delta T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the gamma/delta T cells to kill cancer cells. The killing ability of gamma/delta T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that gamma/delta T cells induce apoptosis in tumor cells. Our study supports the usefulness of gamma/delta T cells in future development of immunotherapy for cervical cancer. PMID- 24228384 TI - Differential microglial and astrocytic response to bacterial and viral infection in the developing hippocampus of neonatal rats. AB - Polyinosinic:polycytidylic acid (Poly I:C; 5 mg/kg body weight, ip) and lipopolysaccharide (LPS; 0.3 mg/kg body weight, ip) induced microglial and astrocytic activation in Sprague Dawley rats. Higher microglial and astrocytic activities were noticed in Poly I:C infused rats throughout the hippocampus till postnatal day 21 with a comparatively weaker response in LPS group. However, LPS induced inflammation persisted even after postnatal day 21, indicating thereby, that the Poly I:C (viral mimic) produces an acute inflammation, while LPS (bacterial endotoxin) produces chronic inflammation when exposed during early neonatal life. PMID- 24228385 TI - In vitro cytotoxicity testing of new generation oxazaphosphorines against human histiocytic lymphoma cells. AB - Oxazaphosphorines belong to a group of alkylating agents. Mafosfamide cyclohexylamine salt (D-17272), 4-hydro-peroxy-cyclophosphamide (D-18864) and glufosfamide (D-19575, beta-D-glucose-isophosphoramide mustard) are new generation oxazaphosphorines. The objective of the present study was to compare the cytotoxic action of these oxazaphosphorine compounds against human histiocytic lymphoma U937 cells. The chemical structures of the oxazaphosphorines were responsible for the different responses of U937 cells. The cytotoxic effects of D-17272, D-18864, and D-19575 on U937 cells depended on the agent tested, its dose, and the time intervals after the oxazaphosphorine application. Among the oxazaphosphorine agents, D-18864 appeared to be the most cytotoxic, and D-19575 was characterized by the lowest cytotoxicity. The in vitro cytotoxic activities of the oxazaphosphorines were strongly associated with their cell death inducing potential. PMID- 24228386 TI - Mollusc C-reactive protein crosses species barrier and reverses hepatotoxicity of lead in rodent models. AB - Achatina fulica C-reactive protein (ACRP) reversed the toxic effects of lead nitrate both in vivo in mice and in vitro in rat hepatocytes restoring the basal level of cell viability, lipid peroxidation, reduced glutathione and superoxides. Cytotoxicity was also significantly ameliorated in rat hepatocytes by in vitro pre-treatments with individual subunits (60, 62, 90 and 110 kDa) of ACRP. Annexin V-Cy3/CFDA dual staining showed significant reduction in the number of apoptotic hepatocytes pre-treated with ACRP. ACRP induced restoration of mitochondrial membrane potential was remarkable. ACRP pre-treatment prevented Pb-induced apoptosis mediated by caspase activation. The antagonistic effect of ACRP may be due to scavenging of reactive oxygen species which maintained the homeostasis of cellular redox potential as well as reduced glutathione status. The results suggest that ACRP crosses the species barrier and it may be utilized as a viable exogenous agent of cytoprotection against heavy metal related toxicity. PMID- 24228387 TI - Phytomodulatory potential of lycopene from Lycopersicum esculentum against doxorubicin induced nephrotoxicity. AB - An elevated level of serum urea and creatinine was observed in doxorubicin (DOX) treated animals indicating DOX-induced nephrotoxicity. Enhanced lipid peroxidation (LPO) in the renal tissue was accompanied by a significant decrease in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. Administration of lycopene (LycT) extracted from tomato to DOX treated mice showed a significant reduction in serum creatinine and urea levels which were associated with significantly low levels of LPO and significantly enhanced level of GSH and related antioxidant enzymes activity (GPx, GR and CAT) when compared to DOX group. Histopathological analysis revealed severe damage in the renal tissue of DOX treated animals. However, animals pretreated with LycT were observed to have reduced damage. Thus, from present results it may be inferred that lycopene may be beneficial in mitigating DOX induced nephrotoxicity in mice. PMID- 24228388 TI - Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats. AB - The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats. PMID- 24228389 TI - Cardioprotective effect of methanolic extract of Marrubium vulgare L. on isoproterenol-induced acute myocardial infarction in rats. AB - Isoproterenol injection (100 mg/kg; sc) produced changes in ECG pattern including ST-segment elevation and suppressed R-amplitude. The methanolic extract of M. vulgare at doses of 10, 20, and 40 mg/kg significantly amended the ECG changes. A severe myocardial necrosis and edematous along with a sharp reduction in the arterial blood pressure, left ventricular contractility (LVdP/dt(max or min)), but a marked increase in the left ventricular end-diastolic pressure (LVEDP) were seen in the isoproterenol group. All parameters were significantly improved by the extract treatment. The extract (10 mg/kg) strongly increased LVdP/dt(max). Similarly, treatment with 40 mg/kg of M. vulgare lowered the elevated LVEDP and the heart to body weight ratio. In addition to in vitro antioxidant activity, the extract suppressed markedly the elevation of malondialdehyde levels both in serum and in myocardium. The results demonstrate that M. vulgare protects myocardium against isoproterenol-induced acute myocardial infarction and suggest that the effects could be related to antioxidant activities. PMID- 24228390 TI - Antihypertensive and vasorelaxant effects of ethanol extract of stem barks from Zanthoxylum rhoifolium Lam. in rats. AB - Administration of ethanol extract of stem bark from Z. rhoifolium (EEtOH-ZR) induced hypotension associated with a dual effect in heart rate in normotensive rats. This response was highlighted in spontaneously hypertensive rats (SHR). In rat superior mesenteric artery rings, the cumulative addition of EEtOH-ZR (0.1 750 microg/mL) on a phenylephrine-induced pre-contraction (10(-5) M) promoted a vasorelaxant effect by a concentration-dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl-induced pre contractions (80 mM). EEtOH-ZR attenuated contractions induced by cumulative addition of CaCl2 (10(-6)-3 x 10(-2) M) in depolarizing medium without Ca2+ only at 500 or 750 microg/mL. Likewise, on S-(-)-Bay K 8644-induced pre-contractions (10(-7) M), the EEtOH-ZR-induced vasorelaxant effect was attenuated. EEtOH-ZR (27, 81, 243 or 500 microg/mL) inhibited contractions induced by cumulative addition of phenylephrine (10(-9) - 10(-5) M) in endothelium-denuded preparations or by a single concentration (10(-5) M) in a Ca(2+)-free medium. The involvement of K+ channels was evaluated by tetraethylammonium (3 mM); the EEtOH-ZR-induced vasorelaxation was not attenuated. Thus, calcium influx blockade through voltage operated calcium channels (CavL) and inhibition of calcium release from intracellular stores are probably underlying EEtOH-ZR-induced cardiovascular effects. PMID- 24228391 TI - Ultrastructural changes and oxidative stress markers in wild and cultivar Sesamum orientale L. following Alternaria sesami (Kawamura) Mohanty and Behera. inoculation. AB - Alternaria sesami causes leaf spot disease in Sesamum orientale. Conidium germination, inoculation, penetration and colonization of the pathogen on the plant surfaces were studied using scanning electron microscopy. Electron microscopy analysis revealed multiple germ tubes from conidium that spread in all direction across the leaf surfaces. Penetration in the plant surface occured, directly through the epidermis or via stomata with or without the appressoria formation. Hyphal penetration continued through the substomata cavity and some of hyphal branches grew in the intercellular space of mesophyll tissue. Hyphal toxin, caused cell and cell wall damages. Changes in different biochemical parameters in the diseased sesame plants (both in wild and cultivar) were compared to control. Transmission electron microscopy showed structural changes in the chloroplast of diseased plants. Isozyme pattern and assays of different enzymes, namely catalase, acid phosphatase and peroxidase expressed varied level of activities. Meanwhile, esterase, polyphenol oxidase and superoxide dismutase in diseased plants showed remarkable levels compared to control. Due to the infection, chlorophyll content, carbohydrates and total soluble protein decreased whereas free amino acid, proline, phenols and disease-related proteins increased in the host plants. Differential SDS-PAGE band profiling of total soluble proteins were also observed in plants due to the infection. PMID- 24228392 TI - An OBVIOUS update: MSD on the run. PMID- 24228393 TI - Total hip arthroplasty as treatment for avascular necrosis secondary to slipped capital femoral epiphysis in a pre-teen. AB - BACKGROUND: While the treatment for avascular necrosis (AVN) secondary to slipped capital femoral epiphysis (SCFE) varies, it is rare that a pre-teenager will undergo a total hip arthroplasty (THA) in efforts to relieve pain and maintain function. METHODS: A-10-year old female sustained an unstable SCFE while playing on wet grass. Unfortunately, her femoral head demonstrated significant AVN after surgical hip dislocation. All treatment options were discussed with the patient and her family. The decision of the family was to have the patient undergo a THA. RESULTS: Approximately one year after her injury, a ceramic on ceramic THA was performed. Her post-operative Harris Hip Scores increased dramatically and she was able to walk without crutches for the first time since her injury. At one year post operatively, the patient was no longer taking narcotics, losing weight, and returned to her sporting activities. CONCLUSION: THA for SCFE in pre teenagers is not a norm and should be considered on a case by case basis. This case report demonstrates a successful outcome and a review of options for the treatment of AVN secondary to SCFE. PMID- 24228394 TI - HIPAA compliance deadline approaching: five steps to ensure you are ready. AB - The September 23, 2013, deadline for covered entities, business associates, and their subcontractors to comply with new HIPAA rules is fast approaching. Now is the time to ensure HIPAA compliance before the deadline arrives and avoid any penalties that could result from failure to act. PMID- 24228395 TI - Knowledge is power: how to avoid six-figure ADA lawsuits. PMID- 24228396 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: presidential lecture; internal medicine for variability among individuals]. PMID- 24228397 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 1. What we have discovered in Hokkaido COPD Cohort Study]. PMID- 24228398 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 2. Strategy for the treatment of hypertension in chronic kidney disease, focusing on Na regulation]. PMID- 24228399 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 3. In pursuit of overcoming pneumonia]. PMID- 24228400 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 4. Recent progress of research and clinics in inflammatory bowel disease]. PMID- 24228401 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 5. Neurological involvement in connective tissue diseases]. PMID- 24228402 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 1. Frontier of the regenerative medicine; introduction]. PMID- 24228403 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 1. Frontier of the regenerative medicine; 1) Regenerative medicine for digestive organs and kidney]. PMID- 24228404 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 1. Frontier of the regenerative medicine; 2) Clinical application of iPS cells in cardiovascular field]. PMID- 24228405 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 1. Frontier of the regenerative medicine; 3) Regenerative medicine for neurological disorders]. PMID- 24228407 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; introduction]. PMID- 24228406 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 1. Frontier of the regenerative medicine; 4) Perspective on regenerative medicine for spinal cord injury using iPS cell--from bench to bedside]. PMID- 24228408 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; 1) Abnormalities in hematopoietic stem cells: congenital immunodeficiencies]. PMID- 24228409 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; 2) Human leukemic stem cell]. PMID- 24228410 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; 3) iPS cell technology for neurodegenerative disease]. PMID- 24228411 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; 4) The intestinal epithelial stem cells and cancer stem cells]. PMID- 24228412 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Diseases originated from stem cell abnormalities; 5) Stem cell disorders and epigenetics]. PMID- 24228413 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; introduction]. PMID- 24228414 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 1) Overview of guidelines: concepts of making clinical practice guidelines and discussion on their social impacts, (1) Breast cancer practice guideline]. PMID- 24228415 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 1) Overview of guidelines: concepts of making clinical practice guidelines and discussion on their social impacts. (2) Evidence-based practical guideline for the treatment of diabetes in Japan]. PMID- 24228416 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 1) Overview of guidelines: concepts of making clinical practice guidelines and discussion on their social impacts. (3) Guideline for managements of hypertension--concept and social significance]. PMID- 24228417 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 2) Clinical guidelines and consensus development]. PMID- 24228418 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 3) Impact, evaluation and legal issues of clinical practice guidelines]. PMID- 24228419 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 3. Social impacts and controversial points of clinical practice guidelines; 4) Guidelines in Japan and in the world]. PMID- 24228420 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security; introduction]. PMID- 24228421 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 1. Clinical autopsy: need for countermeasures against its declining rates]. PMID- 24228422 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 2. Application of autopsy imaging and present situation]. PMID- 24228423 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 3. What is the determining of cause of death for neurologists?]. PMID- 24228424 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 4. Investigation of cause of death in cardiovascular disease--current status and problems]. PMID- 24228425 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 5. Toward the infrastructural development of the death investigation system in Japan--from a lawyers' view]. PMID- 24228426 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Panel discussion: Development of a social system for the best medical quality and security: 6. From model project of investigation system for death associated with medical practice to the establishment of independent organization for professional investigation]. PMID- 24228427 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 1. Pathophysiology and treatment for autoimmune thyroid disease]. PMID- 24228428 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 2. Pathophysiology and treatment of pancreatitis]. PMID- 24228429 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 3. Molecular pathogenesis of leukemia]. PMID- 24228430 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 4. Spinocerebellar degeneration: recent progress]. PMID- 24228431 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 5. Recent advances in vasculitis]. PMID- 24228432 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 6. Pathophysiology of heart failure and medical treatment]. PMID- 24228433 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 7. Tuberculosis care and prevention]. PMID- 24228434 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 8. Risk and management of infectious complications in patients with autoimmune diseases treated with biologicals]. PMID- 24228435 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 9. How to use diuretics based on pathophysiology?]. PMID- 24228436 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 10. Diagnosis and treatment for idiopathic pulmonary fibrosis]. PMID- 24228437 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 11. Multiple sclerosis (MS) and neuromyelitis optica (NMO)]. PMID- 24228438 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 12. Blood transfusion and adverse events--an unrecognized and underestimated clinico-pathological condition]. PMID- 24228439 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 13. Cardiovascular imaging: present status and future perspective]. PMID- 24228440 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 14. Training reform for general internal medicine in Japan]. PMID- 24228441 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 15. Treatment of diabetic nephropathy]. PMID- 24228442 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 16. Pathogenesis and treatment of gallstone diseases]. PMID- 24228443 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 17. Characteristics of lung cancer in Japanese patients and therapy]. PMID- 24228444 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 18. Present status of dialysis therapy]. PMID- 24228445 TI - [110th Scientific Meeting of the Japanese Society of Internal Medicine: Educational lecture: 19. Imported infectious diseases]. PMID- 24228446 TI - [Archetypal scenery of a physician]. PMID- 24228447 TI - [Comparison of the efficacy of ropivacaine and that of levobupivacaine for postoperative epidural analgesia in patients undergoing gynecological open abdominal surgery]. AB - BACKGROUND: Postoperative analgesia is important in patients undergoing open abdominal surgery. We prospectively compared the efficacy of ropivacaine and that of levobupivacaine for postoperative epidural analgesia in patients undergoing gynecological open abdominal surgery. METHODS: Fifty-two ASA 1-2 patients scheduled for gynecological open abdominal surgery under combined general and epidural anesthesia were enrolled and randomized into two groups. In ropivacaine group (n = 26) the patients received 0.187% ropivacaine and fentanyl 3.2 microg x ml(-1) for postoperative epidural analgesia. In levobupivacaine group (n = 26) the patients received 0.187% levobupivacaine and fentanyl 3.2 microg ml(-1). Visual analogue scale (resting pain and pain on mobilization), the amount of rescue analgesics and epidural anesthesia related adverse events such as hypotension, nausea and vomiting were observed for 48 hours after surgery. RESULTS: There were no differences in visual analogue scale at all intervals between the two groups. In levobupivacaine group the patients used less amounts of rescue analgesics than ropivacaine group (P = 0.01). There were no differences in the incidences of postoperative hypotension, nausea and vomiting between the two groups. CONCLUSIONS: Both 0.187% ropivacaine and levobupivacaine similarly provide appropriate postoperative epidural analgesia for patients undergoing gynecological open abdominal surgery. PMID- 24228448 TI - [Possible predictors of discontinuation of basal-flow of postoperative patient controlled analgesia]. AB - BACKGROUND: The purpose of this study was to identify possible predictors of discontinuation of basal-flow of postoperative patient-controlled analgesia. METHODS: We reviewed postoperative pain assessment records by the postoperative pain service team from April 2010 to July 2011 in which surgical patients were provided with intravenous or epidural patient-controlled analgesia (IV-PCA or Epi PCA). From these data, we extracted cases with discontinuation of basal-flow of PCA, and candidate variables such as patients' characteristics, preoperative and intraoperative variables were assessed. Predictors with significant univariate association (P < 0.20) with the primary outcome were used to construct multivariable logistic regression models. RESULTS: We enrolled 685 patients for IV-PCA and 606 for Epi-PCA and obtained discontinuation groups (105 and 73 cases, respectively) with this cohort data. Results of multivariate analysis showed female, non-laparotomy, low body weight, and non-droperidol as independent risk factors for IV-PCA and low body weight, no-co-existing disease, and gastrointestinal surgery for Epi-PCA. There were no significant differences in pain intensity between discontinuation and non-discontinuation cases. The primary cause of discontinuation was PONV for IV-PCA and hypotension for Epi-PCA, respectively. CONCLUSIONS: We should apply IV-PCA for female slender surgical patients undergoing non-laparotomy with great caution and provide prevention for PON. We should pay attention to incidence of postoperative hypotenion when we administer Epi-PCA to slender gastrointestinal surgical patients without co existing disease. PMID- 24228449 TI - [General anesthesia for lung resection in 7 patients with forced expiratory volume in 1 second of less than 1l]. AB - Preoperative forced expiratory volume in 1 second less than 1 l is a risk factor for anesthesia. We report perioperative management and prognosis of 7 patients with restricted lung function who underwent lung resection under general anesthesia. We assessed the patients preoperatively from the point of view of heart-lung functions such as predicted postoperative forced expiratory volume in 1 second greater than 0.8 l, an ability of walking on the level for more than 5 minutes at his own speed without a rest, presence of hypercapnia, and degree of pulmonary hypertension. One patient was extubated on the first postoperative day because of an asthmatic attack, whereas the remaining 6 patients were extubated in the operating room. Although 1 patient developed postoperative complications of lung air leakage and pneumonia, he recovered with conservative therapy. All patients were discharged without any sequela. We were able to manage high-risk patients with limited lung functions successfully during the perioperative period without serious complications. PMID- 24228450 TI - [Pediatric use of cuffed tracheal tubes under general anesthesia]. AB - BACKGROUND: Although the use of cuffed tracheal tubes (CTT) in children less than 8 years of age has increased, the criteria for selecting CTTs of appropriate sizes have not been determined. METHODS: To study the criteria for choosing tubes of appropriate sizes (internal diameter: 4.0, 4.5, 5.0, or 5.5mm), we intubated 51 children aged 2-8 years under general anesthesia using an original protocol. We excluded 2 patients who received 4.0-mm tubes; thus, the outcomes in 48 patients were analyzed statistically. RESULTS: A larger CTT was replaced with a smaller one in 1 patient, and a CTT was replaced with an uncuffed tracheal tube (UTT) in another patient (excluded from analysis). No tube changes were required in 49 patients. Post-extubation stridor was observed in 3 patients. The 4.5-mm tubes seemed appropriate in 12 cases because average airway leakage in these cases was > 10%; 5.0- and 5.5-mm tubes did not seem appropriate in 17 and 19 cases, respectively, because the leakage was < 10% of the tidal volume. CONCLUSIONS: We recommend the pediatric use of CTTs because of the very low tube exchange ratio and the acceptable incidence of stridor. However, the protocol may require modification. PMID- 24228451 TI - [Resveratrol did not prevent sevoflurane-induced neuroapoptosis in the neonatal mice brain]. AB - BACKGROUND: In an animal model, neonatal exposure to sevoflurane induces neuroapoptosis, leading to memory deficits in adulthood. A recent study showed that resveratrol (20 mg x kg(-1)) prevent alcohol-induced cognitive deficits and neural apotosis in rat pups postnatally exposed to ethanol. We investigated if resveratorol prevent sevoflurane induced neuroapotosis. METHODS: Six-day-old mice were divided into two groups: resveratorol and control groups. Pups were given resveratrol orally 24h and 1h before sevoflurane anesthesia. Anesthesia was maintained for 6h. After anesthesia, apotosis was evaluated by immunohistochemical staining for activated caspase-3. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apotosis. RESULTS: Neonatal exposure to sevoflurane induced severe neuroapotosis. There were no differences between control groups and resveratrol groups with regards to immunohistochemical staining and western blot analysis. CONCLUSIONS: Resveratrol did not prevent sevoflurane-induced neuroapoptosis in the neonatal mice brain. PMID- 24228452 TI - [A case of extensive pulmonary atelectasis after intubation in a patient undergoing elective tympanoplasty]. AB - A 33-year-old male, without significant medical history, underwent elective tympanoplasty. It was difficult to manage his airway because of overbites, small jaw, and short neck. After intubation, his left chest revealed obvious abnormality in sound and movement, and showed free air in the mediastinum on X ray. CT revealed extensive atelectasis. Although he is a current smoker, the length of preoperative smoking cessation necessary to decrease postoperative pulmonary complications is not clear. This case demonstrates the importance of preoperative preparation including education in smoking damage. PMID- 24228453 TI - [Perioperative management of a patient with anomalous origin of the left coronary artery from the pulmonary artery]. AB - Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease, also known as Bland-White-Garland (BWG) syndrome. Mitral valve regurgitation secondary to papillary muscle dysfunction due to myocardial ischemia and progressive left ventricular dysfunction are major clinical manifestations of BWG syndrome. We report perioperative management of a five-year old patient with BWG syndrome who underwent the Takeuchi procedure making an intrapulmonary baffle using anterior pulmonary artery wall. General anesthesia was maintained with inhalation of sevoflurane in 25-40% oxygen and continuous infusion of remifentanil. Since a decrease in pulmonary artery pressure could induce coronary steal phenomenon, we ventilated the patient with minimally required FI(O2) to maintain Sp(O2) 98-100%, and maintained Pa(CO2) between 40 and 50 mmHg to avoid myocardial ischemia before the induction of cardiopulmonary bypass (CPB). We started continuous infusions of nitroglycerin and milrinone after the initiation of CPB, which were continued through the post-CPB period. The patient was transferred to the ICU and the postoperative course was uneventful. There are two key points in the management of BWG syndrome : the balance between systemic and pulmonary artery pressure in pre-CPB period, and left ventricular support including both inotropes and vasodilators in post-CPB period. PMID- 24228454 TI - [Intraoperative evaluation of visceral arteries by transesophageal echocardiography during aortic fenestration]. AB - 76-year-old man was diagnosed with DeBakey type IIIb acute aortic dissection, for which he underwent axillo-femoral bypass surgery. Two days postoperatively, hematochezia developed suddenly. Laboratory data revealed AST 5,088 IU x l(-1), ALT 3,822 IU x l(-1), and CK 27,746 IU x l(-1) suggesting intestinal malperfusion due to stenosis of the celiac artery (CEA) and superior mesenteric artery (SMA). The abdominal aorta and visceral arteries were evaluated by transesophageal echocardiography (TEE). Color Doppler imaging revealed increased blood flow velocity (4.0 m x sec(-1)) in CEA due to the stenosis, while that in SMA was decreased. Open abdominal aortic fenestration was performed. The aorta was clamped at the level of the infra-renal and inferior mesenteric arteries, and the septum between the false and true lumens was resected. On postoperative TEE assessment, CEA stenosis was resolved, and flow velocity was improved (3.0 m x sec(-1)). Color Doppler imaging demonstrated that fenestration resulted in recovery of SMA perfusion. Aortic fenestration is useful in the treatment of ischemic complications of aortic dissection. Its advantages include minimal invasiveness and short operative time. Bypass surgery and reoperation were avoided by evaluating visceral arteries by TEE in the case reported here. PMID- 24228455 TI - [Anesthesia for living donor renal transplantation in a patient with Goodpasture's syndrome with a history of repeated alveolar hemorrhage]. AB - A 20-year-old woman was scheduled for living renal transplantation from her mother. She was diagnosed with Goodpasture's syndrome at 8 years of age and had a previous history of alveolar hemorrhage 5 times. She developed renal failure, hypertension and required hemodialysis. She had no history of surgery. Blood test was not remarkable except anemia and elevated blood urea nitrogen and serum creatinine levels. General anesthesia was induced and maintained with fentanyl, remifentanil and propofol. After tracheal intubation, the lungs were mechanically ventilated with a pressure control mode and the peak airway pressure was initially adjusted to 9 cmH2O for maintaining airway pressure at a low level to prevent alveolar injury, which was increased to 12 cmH2O at the end of surgery for maintaining a tidal volume of approximately 250 ml. No hemorrhage was detected in the airway during anesthesia, blood gas data were within the normal range, and the tracheal tube was removed after surgery in the operating room. Postoperative course was uneventful. Antihypertensive agents were discontinued and she was successfully weaned from hemodialysis. PMID- 24228456 TI - [Massive pulmonary thromboembolism during an orthopedic surgery in an obese patient]. AB - Deep venous thrombosis (DVT) and the consequent pulmonary embolism (PE) are devastating complications in orthopedic surgery. We report a 45-year-old male patient who developed PE during an operation of proximal tibia fracture under general anesthesia. On mobilization of knee joint, end-tidal CO2 suddenly decreased from 28 to 18 mmHg. Sp(O2) decreased from 99 to 92%, but blood pressure was maintained. Postoperatively Sp(O2) was maintained 94-95% in room air, but sinus tachycardia over 120 beats x min(-1) continued. On postoperative day 1, the patient experienced dyspnea. In the chest CT scan, massive embolism was found in the bilateral main pulmonary arteries and both middle lobe as well as lower lobe arteries in the right lung. DVT was detected by enhanced CT scan of the lower extremity. This patient had many risk factors for PE such as obesity, smoking, immobilization and lack of thromboprophylaxis. PMID- 24228457 TI - [Spinal paralysis by extradural hematoma following catheter removal]. AB - A 63-year-man with lung cancer underwent right upper lobectomy under general anesthesia combined with thoracic epidural anesthesia. The surgical course was uneventfully completed. On the second postoperative day, he developed complete paralysis below T4 level 1 hour after removal of the epidural catheter. The magnetic resonance imaging (MRI) showed extradural hematoma compressing the spinal cord from T4 to T6 segments. Surgical removal of hematoma was scheduled. However, his neurological condition improved rapidly within a couple of hours, and the surgery was not carried out. The time course of recovery from complete paralysis suggests that extradural hematoma diffused into the extradural space, resulting in a decrease in the epidural pressure. PMID- 24228458 TI - [The efficacy of ultrasound-guided infraorbital nerve block with hockey stick typed probe]. AB - We report a case of ultrasound-guided infraorbital nerve block with a hockey stick typed probe in plane approach. Individual difference of infraorbital anatomy makes it difficult to puncture the infraorbital for a man, and the risks include bleeding, double vision and paranasal sinus puncture. The advantage of ultrasound-guided nerve block has been reported. Compared with conventional land mark method approach, ultrasound technique is thought to be easy to perform, more quickly and safely without any complications. From our results, we have demonstrated that ultrasound-guided infraorbital nerve block assisted by hockey stick typed probe could become one of the safe methods for this purpose. PMID- 24228459 TI - [Anesthetic and perioperative management of a patient with uncontrolled thyrotoxicosis undergoing coronary artery bypass grafting surgery]. AB - Uncontrolled hyperthyroidism is a risk factor of perioperative thyrotoxic crisis. We report a case of a 61-year-old woman with thyrotoxicosis diagnosed with unstable angina pectoris. She needed to have an early scheduled coronay artery bypass grafting surgery, because percutaneous intervention for the left main coronary artery in support of intra-aortic balloon pumping (IABP) resulted in failure. Tachycardia and hyperthermia were observed at admission to the ICU, and hemodynamic parameters suggested high-output heart failure. Preoperative management using antithyroid drug, inorganic iodine, corticosteroid and propranolol stabilized her hemodynamic condition, and then CABG was performed on ICU day 3. Intraoperative and postoperative use of landiolol, a short acting beta blocker, was useful for maintaining hemodynamic stability. Surgery was uneventfully completed and she was extubated on postoperative day 1 following IABP withdrawal. Appropriate preoperative management and perioperative use of the short acting beta blocker were useful for management of the patient with uncontrolled hyperthyroid state. PMID- 24228460 TI - [Low dose vasopressin is effective for catecholamine-resistant hypotension after resection of pheochromocytoma]. AB - The perioperative management of pheochromocytoma is challenging for anesthesiologists and persistent hypotension secondary to cathecholamine depletion after tumor resection can be refractory to treatment. A 64-year-old man underwent right adrenalectomy for treatment of massive pheochromocytoma. Doxazosin administration was started and increased gradually to 12 mg daily. He was premedicated with doxazosin on the day of the surgery. Induction was uneventful but there was a sudden increase of blood pressure with tachycardia on handling of tumor which was controlled by intravenous remifentanil, landiolol, diltiazem, and magnesium sulfate. With dissection of the tumor, the blood pressure dropped to 65/40 mmHg, which was resistant to fluid and cathecholamine treatment. After commencement of low dose vasopressin administration (two boluses of 0.08 U followed by 1.6 U x hr(-1)), blood pressure gradually recovered to normal ranges. Low dose vasopressin can be safely used to treat postadrenalectomy hypotension and also can reduce the cathecholamine dose. PMID- 24228461 TI - [Successful management of sigmoidectomy with sildenafil citrate in a patient with acute exacerbation of chronic thromboembolic pulmonary hypertension]. AB - An 84-year-old woman with pulmonary hypertension (PH) secondary to chronic pulmonary thromboembolism suffered from continuous warfarin dependent bleeding from sigmoid colon cancer. Sigmoidectomy was scheduled to control continuous bleeding. Six hours after discontinuation of anticoagulant therapy for elective sigmoidectomy, the patient showed hypoxia, pulmonary thromboembolism and pulmonary hypertension with right ventricular systolic pressure (RVSP) of 81 mmHg. The operation was postponed and heparin was infused. Since two-day heparinization therapy did not improve PH, oral administration of sildenafil citrate 60 mg daily was initiated. Seven days after initiation of sildenafil administration, RVSP decreased to 49 mmHg without improvement of hypoxia. Sigmoidectomy was performed under general anesthesia. The patient showed severe hypotension managed with noradrenaline and dopamine infusion during and after surgery, resulting from interaction between sildenafil and vasodilators. The patient was discharged 36 days after the operation without complications. PMID- 24228462 TI - [Increase in serum vecuronium concentration following sugammadex administration in a pediatric patient after prolonged sedation]. AB - It is known that blood concentration of rocuronium increases after administration of sugammadex, but this is not clear in the case of vecuronium. We report a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. A 19-month old girl weighing 7.8 kg had a history of aortic valvuloplasty at 4 months of age due to truncus arteriosus. She presented again to our hospital due to aortic regurgitation. She underwent aortic valvuloplasty and then aortic valve replacement. The postoperative course was complicated with severe heart failure and acute kidney injury requiring peritoneal dialysis. For that reason she required long-term sedation including administration of a large amount of muscle relaxant due to severe low cardiac output syndrome after aortic valvuloplasty. A total of 615 mg (79 mg x kg(-1)) of vecuronium was administered over a period of 24 days. On weaning from mechanical ventilation, 125 mg (16 mg x kg(-1)) of sugammadex was given. Vecuronium concentration measured by high-performance liquid chromatography (HPLC) was 5.03 ng x ml(-1) before sugammadex administration and increase to 13.98 ng x ml(-1) after that. However, blood concentration of metabolic products of vecuronium did not exceed the lower limits of measurement in each sample. She was successfully weaned from mechanical ventilation without recurarizarion. Serum concentration of vecuronium increased after administration of sugammadex because extravascular vecuronium was redistributed to intravascular space according to the concentration gradient induced by binding and clathration of vecuronium. The measured values of vecuronium after sugammadex administration on HPLC represented the total amount of free vecuronium and vecuronium combined with sugammadex. Recurarization might occur after sugammadex reversal in patients after long-term administration of vecuronium, especially if relatively smaller doses of sugammadex were given. We experienced a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. There is a risk of recurarization after sugammadex reversal in patients after long-term administration of vecuronium. PMID- 24228463 TI - [A case of rocuronium-induced anaphylactic shock successfully treated with sugammadex]. AB - We report a case of a 19-year-old male with rocuronium-induced anaphylactic shock. He was scheduled for endoscopic sinus surgery for chronic sinusitis under general anesthesia. Induction of anesthesia was done with fentanyl, propofol and sevoflurane. Just after administration of rocuronium, he developed tachycardia with extended exanthema on the face, anterior chest wall and abdomen. He was difficult to ventilate manually with mask and then intubated without difficulty. The carotid arterial pulse was not palpable and adrenaline was given intermittently to maintain blood pressure. Although the systolic blood pressure increased to 80 mmHg, hemodynamics was unstable with adrenaline. Sugammadex was then given and the blood pressure became stable without adrenaline. Exanthema also disappeared gradually. He was then transferred to ICU and extubated without any sequela. The plasma beta-tryptase increased to 46 microg x l(-1) during the shock state and returned to 14.1 microg x l(-1) 8 hrs after the event. The blood hemoglobin level also increased to 21.3 g x dl(-1) during the shock state and returned to 17.2 g x dl(-1) during the recovery phase. The laboratory data showed a marked increase in vascular permeability caused by rocuronium-induced anaphylactic shock. PMID- 24228464 TI - [Anaphylaxis needing adrenaline administration during anesthesia: a 7-year single institution study]. AB - BACKGROUND: Adrenaline is the key treatment for acute anaphylaxis; however, it is difficult to use it appropriately in terms of dosage and timing. If used incorrectly, adrenaline can cause cardiac infarction, stroke, recurrence and other problems. METHODS: We collected data of suspected anaphylaxis from records in our anesthesia department between April 2005 and March 2012. All cases where the skin of patients turned red and blood pressure decreased continuously were included. We analyzed the usage of adrenaline in these cases. RESULTS: Six (0.034%) suspected anaphylaxis cases were analyzed from a total of 27,597 anesthesia cases. Adrenaline was administered subcutaneously in 2 cases, intravenously in 3 cases, and with and infused in 1 case. In the 4 cases with intravenous administration, the median dose was 0.52 (range : 0.02-1.6) mg. Following decreased and unstable blood pressure, adrenaline was initiated after a median of 12.5 (5-25) min, and blood pressure returned to normal after 20 (5-95) min. Patients were extubated 19 (4-24) hours after observation of anomalous blood pressure. No aftereffects or recurrences were observed. CONCLUSIONS: Adrenaline was administered appropriately in terms of dosage, but timing should have been earlies in 3 of 6 cases. PMID- 24228465 TI - [A case of tracheal intubation for apnea with epidural opioid in recovery room after operation under general anesthesia]. AB - We report a 68-year-old, American Society of Anesthesiologists Class I (ASA I), female patient scheduled for malignant uterine adnexal tumor surgery and revascularization for ovarian cancer. An epidural catheter was inserted at T12-L1 for 5 cm. Anesthesia was induced with remifentanil (0.25 microg x kg(-1) x min( 1)), sevoflurane (5%) and rocuronium (30 mg). Anesthesia was satisfactorily maintained after intubation with sevoflurane (1.5%) and remifentanil (0.2 microg x kg(-1) x min(-1)). We extubated the patient because spontaneous breathing and consciousness were observed. We intubated the patient immediately for apnea that occurred after extubation. The patient made an uneventful recovery after naloxone administration. In pharmacokinetic simulation, on the assumption that epidural administrated fentanyl was carried to blood content promptly, effect concentration to cause respiratory depression was not reached. Postoperative apnea was rationalized as follows; tardy respiratory depression with the epidural administration, and unexpected dosage of the residual fentanyl in the catheter. PMID- 24228466 TI - [Anesthetic management of a patient with hemophilia B during scoliosis surgery]. AB - Posterior spinal fusion for scoliosis was planned in a 14-year-old male patient with hemophilia B. Preoperative examination showed factor IX activity of 8.4% with no inhibitor development. A perioperative dosage schedule was prepared after examining the pharmacokinetics of recombinant coagulation factor IX in order to maintain levels of perioperative factor IX activity at < or = 80% for the first 6 days (days 0-6), and > or = 40% for days 7-14 postoperatively. The dose of recombinant coagulation factor IX was adjusted to maintain factor IX activity above 80%, while measuring coagulation activity every hour during the surgery. The patient showed a favorable course without hemorrhagic tendency. We could safely manage anesthesia without requiring allogeneic blood transfusion. PMID- 24228467 TI - [A case of transfusion-related acute lung injury following platelet transfusion during the cervical supine surgery]. AB - We report a case of possible transfusion-related acute lung injury (TRALI). The patient is a 69-year-old man who underwent cervical supine surgery Platelet products were transfused pre-and intra-operatively. At the end of the operation, he was fully awake and extubated. Shortly after extubation he showed low oxygen saturation, and we started bag-mask ventilation. A chest X-ray revealed bilateral diffuse pulmonary edema without cardiac enlargement. Thus we inserted endotracheal tube and started positive pressure assist ventilation. Hypoxemia was improved gradually, and he was re-extubated on the fourth day after the operation. The prevalence of TRALI reactions is reported to be high for platelet product and is influenced by patients' underlying clinical condition. Serum anti leukocyte antibody was negative, but we suspected the possibility of TRALI based on the clinical findings. PMID- 24228468 TI - [Anesthetic management in a patient with head and neck burn by asphalt]. AB - In cases of facial burns caused by molten asphalt, examination for possible airway burns and early removal of the asphalt should be carried out to prevent chemical-induced tissue damage and infection. However, asphalt that has adhered to tissues is difficult to remove. A 35-year-old male with burns caused by molten asphalt was scheduled for emergency debridement. He had 6% body surface area burns on his face and neck. He was not able to open his eyes due to the adherence of asphalt. His respiratory condition was stable and a perioperative fiberoptic view revealed no airway burns. After awake intubation, orange peel oil was used to remove the asphalt from his face and eyes. Since orange peel oil does not contain any harmful substances, it is effective for removing asphalt without causing tissue damage. PMID- 24228469 TI - [A case of continuous epidural anesthesia for pain relief in a pregnant woman with uterine myoma in the second trimester of pregnancy]. AB - We present a case of continuous epidural anesthesia for a pregnant woman with uterine myoma. A 35-year-old pregnant woman at 16 weeks of pregnancy became aware of pain in the right lower abdomen. She was diagnosed with painful degenerating uterine myoma. Acetaminophen failed to control pain, and intramuscular pentazocine was only weakly effective. To avoid increasing the analgesic dose, we resorted to continuous epidural anesthesia starting at 18 weeks of pregnancy. The pain was improved remarkably by continuous epidural anesthesia with 0.2% ropivacaine. The epidural catheter was removed 6 days after the initiation of treatment. Since then there was no recurrence of pain. Besides providing good analgesic effect, the epidural anesthesia can help suppress uterine contractions and improve blood flow to the myomatous parts of the uterus. Therefore, it can be a suitable method of pain control in women with uterine myomas in mid-pregnancy. PMID- 24228470 TI - [A virtual respiratory model of the concentration of each gas in the alveoli as a function of time when the inspired and expired volumes are equal]. AB - A specific mathematical ventilation model was assumed to derive a new expression for the concentration of each gas in the alveoli with only the ventilatory parameters or with the functional residual volume, tidal volume, anatomical dead space, and end-tidal gas concentration. The inequality derived from the mean concentration equation showed that, if the I to E ratio was inversed, the end tidal P(CO2) was higher than the mean alveolar P(CO2), which was almost equal to the sampled arterial P(CO2). In the present model, at the inverse ratio ventilation (IRV), the end-tidal P(CO2) was higher than the arterial P(CO2). The mean equation provided not only the A-a D(O2), but also the a-AD(CO2). The A aD(O2) was evaluated with respect to cardiac output. In the equation, I is the duration of inspiration; E is the duration of expiration; P(CO2) is the carbon dioxide tension; A-aD(O2) is the mean alveolar/mean arterial P(O2) difference; P(O2) is the oxygen tension; and a-AD(CO2) is the mean arterial/mean alveolar P(CO2) difference. PMID- 24228471 TI - [The effectiveness of a system using re-useable linens to reduce the expense of surgical operations]. AB - We introduced a system that uses re-useable linens for surgical operations in 2008. After 3 years from introduction we were able to reduce the expense of about yen 4,340,000 per year and CO2 production of 9,548 kg CO2 x m(-2) per year. We were convinced of the effect on reducing the expense of surgical operations and of decreasing the level of CO2 production that leads to global warming. PMID- 24228472 TI - [On suggestion and its related problems]. AB - Recently, intensive discussions about dissociative disorders have led to the rediscovery of the psychology of P. Janet, that has been under the shadow of Freud's psychoanalysis. Nevertheless, psychiatry, "Schulpsychiatrie" in German, has still paid little attention to the suggestion with which Janet has occupied himself throughout his long career. In this paper, the author examined suggestion from another point of view other than psychodynamic. It is presented that Freud reduced suggestion to a specific relation between an active subject and a passive object, as his precursors, F.A. Mesmer and R. de Puysegur did the same. In contrast, Janet's early studies influenced by the philosophy of M. de Biran seem to focus on another aspect of suggestion. From this aspect, suggestion is based on a spontaneous intersubjective process that should be expressed by the middle voice. Referring to H. Bergson, with whom Janet corresponded, the author pointed out that one is not always one's own self that reflects one's whole life history, regardless of the presence/absence of mental abnormality, as is the case with a person under suggestion. Taking into account these factors of suggestion, i. e., the middle voice and fragile selfhood that is not firmly rooted in one's own life history, the author investigated hysteria as a distinct phenomenon that has a particularly close relation with suggestion. Furthermore, depersonalization and schizophrenia were discussed concerning their relation with hysteria. In this approach, the author suggested that the unconscious could be topographically localized not only in a deep portion of the mental apparatus, but also in its most superficial portion, unlike in the case of Freud's psychoanalysis. PMID- 24228474 TI - [Clinical features, treatments and outcome of obsessive-compulsive disorder (OCD) focusing on the assessment and characteristics of patients with treatment refractory OCD]. AB - Obsessive-compulsive disorder (OCD) is fairly common, with prevalence estimates ranging from 1 to 2%. OCD is generally described as having a chronic course with periods of waxing and waning of symptoms, and most individuals with OCD are at risk for other comorbid psychiatric disorders such as major depression. It is associated with considerable impairment and disability, in that individuals with OCD often experience severe social and interpersonal difficulties, familial dysfunction, occupational problems and impaired quality of life. Indeed, WHO classifies OCD as one of the top 10 most debilitating illnesses. Despite the proven effectiveness of cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) in the treatment of OCD, these 2 treatment strategies have demonstrated inadequate responses in at least 40% of OCD patients. Moreover, even when the best available treatments are applied, a number of patients remain severely affected and experience treatment-refractory OCD. Long-term follow-up (up to 40 years) studies also suggest that OCD often results in a chronic and lifelong condition with low rates of remission and with a relatively high probability of relapse. Thus, a "treatment-refractory" status should be assessed in each OCD individual according to responses to all available therapeutic alternatives, along with the long-term course and outcome. For further exploration of the treatment strategies for OCD patients assessed as "treatment-refractory", definition of the condition as well as the optimization and standardization of the currently best available treatments is needed. In particular, taking into account the psychopathologically and biologically heterogeneous nature of OCD, optimal and rational treatment strategies should be independently examined for each distinct OCD subtype. Further advance of social support and educational systems may also be helpful to promote earlier intervention for the treatment of individuals at high risk of developing chronic or treatment-refractory OCD. PMID- 24228473 TI - [Clinical experience with clozapine in 55 cases of treatment-resistant schizophrenia]. AB - Up until October 2012, Kohnodai Hospital had introduced clozapine treatment for 55 cases of treatment-resistant schizophrenia. In all cases, previous antipsychotic medication was discontinued the day before clozapine administration began. Of the 55 cases, 45(85%)are continuing clozapine administration, and 40 cases (73%) are receiving outpatient treatment. The average dose of clozapine was 373.1 mg/day (SD : 160.5). Clozapine was administered for a month or more in 51 cases (93%). BPRS scores improved 20% or more in a month's administration of clozapine in 18 of the cases (35%). The average clozapine dose in the improvement cases was 176 mg/day. The average BPRS score had significantly decreased from the baseline at months 1, 3, 6, and 12 after the start of clozapine administration. Of the 33 cases receiving clozapine treatment for 12 months or more, BPRS improved 20% or more in 27 (82%). BPRS improved 20% or more for the first time after clozapine administration within a month in 12 cases (44%), 3 months in 8 cases (30%), 6 months in 5 cases (19%), and 12 months in 2 cases (7%). These results suggest that clozapine should be administered continuously for over 6 months at the least and 12 months if possible to evaluate the efficacy of clozapine treatment. Of the 43 cases receiving outpatient clozapine therapy, the average GAF score improved significantly from the time of ward admission to discharge (20.6 and 42.0, respectively). Clozapine had to be discontinued in 2 cases of leukopenia, 2 cases of neutropenia, 1 case of reduced left ventricular ejection due to pericardial effusion, 1 case of drug eruption, and 1 case of marked hunger. When introducing clozapine for treatment-resistant schizophrenia, it is important to administer it as a monotherapy, slowly increase the dosage to reduce side effects, and achieve a treatment effect at the minimum required dosage. PMID- 24228475 TI - [Definition of treatment-refractory obsessive-compulsive disorder based on cognitive behavioral therapy]. AB - Several lines of evidence have shown that cognitive behavioral therapy (CBT) is more effective than pharmacotherapy for people with obsessive-compulsive disorder (OCD). Not only pharmacotherapy-resistant but also CBT-resistant OCD should be defined. After reviewing previous studies, patients with treatment-refractory OCD may be required to show severe symptoms with a score of at least 28 on the Yale Brown Obsessive-Compulsive Scale (Y-BOCS) even after therapy, and have at least a 5-year history of OCD. I propose CBT-RESISTANT OCD as a term to describe cases of OCD that do not respond to adequate standard CBT of at least 30 hours. Moreover, CBT-REFRACTORY OCD can only be determined if a person has tried intensive CBT (including exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance session) of at least 40 hours after standard CBT. PMID- 24228476 TI - [Treatment-refractory OCD and its biological pathophysiology]. AB - Recently, ample evidence has suggested that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are highly effective treatments for OCD. There are, however, certain patients who are refractory to almost all types of therapeutic intervention. In recent studies, atypical antipsychotic augmentation of SSRIs and deep brain stimulation have been suggested to be effective for these refractory-type patients. Dysfunction of neuro-circuits throughout the frontal cortex and associated subcortical structures is considered to be due to both serotonergic and dopaminergic nerve system impairment. A large number of previous neuroimaging studies identified abnormally high metabolic activities throughout the frontal cortex as well as subcortical and limbic structures. These over-activities are suggested to be biological markers of the treatment response. In addition, structural and nerve connective dysfunction of these regions may be associated with a severe, treatment-resistant, and treatment-refractory status. A treatment-refractory state may be attributable to the clinical subtypes of OCD. Associations between the symptom subtype and brain activity reveal the heterogeneity of OCD. Several correlative analyses have shown distinct neural correlations associated with specific OCD symptom dimensions such as aggression/checking, contamination/cleaning, and hoarding. Overlapping of these neural disturbances will cause treatment-refractory OCD. Another reason for a treatment-refractory state may be comorbid disorders such as major depression and tic disorders. Comorbid depression will aggravate metabolic impairments in the hippocampus and thalamus and cause more severe disturbance of neuro-circuits in OCD. Obsessive compulsive symptom with Tourette syndrome or pervasive developmental disorders will become refractory because of fixation caused by developmental factors and a perceptual element called "just right feeling". There should be a close relationship between neuro-circuit disturbance and a treatment-refractory state. The pathophysiology becomes more complicated due to the symptom subtype and comorbidity. Further investigations are needed to develop effective treatment strategies based on biological evidence. PMID- 24228477 TI - [Treatment-refractory OCD from the viewpoint of obsessive-compulsive spectrum disorders: impact of comorbid child and adolescent psychiatric disorders]. AB - More than a half of patients with OCD are classified as early-onset. Early-onset OCD has been indicated to be associated with a greater OCD global severity and more frequently comorbid with tic disorders and other obsessive-compulsive (OC) spectrum disorders, compared with late-onset OCD. Early-onset OCD patients with severe impairment caused by both OC symptoms and comorbid OC spectrum disorders may be identified as being refractory. Tic disorders and autism spectrum disorder (ASD) are child and adolescent psychiatric disorders included in OC spectrum disorders. OCD comorbid with chronic tic disorders including Tourette syndrome (TS) is specified as tic-related OCD. Tic-related OCD is characterized by the high prevalence of early-onset and sensory phenomena including "just right" feeling. Self-injurious behaviors (SIB) such as head banging and body punching often occur in patients with TS. The patients' concern about SIB is likely to trigger them, suggesting that an impulse-control problem is a feature of TS. More than a half of patients with TS have OC symptoms. When OC symptoms in patients with TS were assessed with a dimensional approach, symmetry dimension symptoms were found most frequently over the lifetime. On the other hand, the severity of aggression dimension symptoms was the most stable during the course among all dimensions. Aggression dimension symptoms also exhibited a close relationship with impairment of global functioning and sensory phenomena. This tendency may be characteristic of tic-related OCD. It is sometimes difficult to differentiate between OC symptoms and restricted, repetitive behaviors which are core symptoms of ASD. Recently, ego-dystonia and insight are considered non-essential to diagnose OCD, whereas high-functioning and/or atypical ASD is recognized as being more prevalent than previously estimated. In this situation, attention to comorbidity of OCD and ASD is increasing, and the prevalence of OCD in children and adolescents with ASD was reported to be about 20%. One study on the impact of comorbid ASD in adults with OCD indicated that comorbid patients had higher scores for the Autism Questionnaire (AQ) subscales of attention switching and imagination but showed little difference in OC symptoms except for the predominance of compulsion compared to patients with pure OCD. "Just right" feeling and impulse-control problems were evident in OC patients comorbid with both ASD and TS. Out of five adults with TS who underwent deep brain stimulation (DBS) because of refractory tics, four had impulse-control problems including SIB, leading to very severe physical injuries in two patients. After DBS, tics and SIB improved in all patients; however, one patient experienced their re aggravation. To improve understanding of and treatment/support for refractory OCD, OC spectrum disorders should also be considered. PMID- 24228478 TI - [Novel treatment strategies for refractory patients with obsessive-compulsive disorder]. AB - Although selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD), response rates to these therapies are 40-60%. There may be many treatment refractory patients who do not respond to several SSRIs and intensive CBT treatment. The current treatment guidelines suggest various strategies for treatment-refractory cases, but there is no established evidence for most of them. Augmentation therapies with antipsychotics and glutamate modulator drugs have yielded some supporting evidence. When all drugs and CBT are ineffective, non-pharmacological treatment including deep brain stimulation (DBS) should be applied. However, it is necessary to establish criteria for treatment-refractory patients and standardize conventional treatment before neuromodulation treatment is applied in Japan. PMID- 24228479 TI - [Social cognition and psychiatry]. AB - Social cognition consists of multiple interpersonal abilities such as emotional facial recognition, the "theory of mind", and empathy. Neural bases of these abilities have been investigated extensively, and key brain structures such as the amygdala, medial prefrontal cortex, insula, and superior temporal sulcus, are called the "social brain" by some researchers. Social cognition has been demonstrated to be an essential determinant of daily functioning in schizophrenia. Progress in social neuroscience, together with advanced neuroimaging technology, promotes our understanding of schizophrenia from the viewpoint of social cognition and the social brain. PMID- 24228480 TI - [Influence of RGPU-207 compound and amiodarone on ion currents in shellfish neurons]. AB - RGPU-207 compound and amiodarone in concentrations of 1, 10, 100 and 1000 microM produce dose-dependent and reversible effects on trans-membrane sodium, calcium, and potassium ion currents of neurons in pond snail and orb snail shellfish. In concentration of 1 microM, both compounds increased the amplitude of potassium ion currents, while not affecting the amplitude of sodium and calcium ion currents. In concentrations of 100 and 1000 microM, dose-dependent suppression of all currents (with predominant potassium ion current suppression) was observed. Under the action of RGPU-207 compound, the kinetics of activation and inactivation of sodium and calcium ion currents was not changed, but the kinetics of activation of the potassium slow current was slowing down. Amiodarone decelerated the inactivation of calcium ion current and accelerated the inactivation of potassium slow current. RGPU-207 compound, in comparison to amiodarone, produces a similar membranotropic effect on the shellfish neurons. PMID- 24228481 TI - [Influence of lithium salt of comenic acid on the state of oxidative processes in brain of stressed animals]. AB - The influence of a new substance, lithium salt of comenic acid, on the oxidative processes in the brain of animals under the conditions of acute and long combined stress has been investigated. It is established that lithium comenate (1 and 2 mg/kg) exhibits pronounced dose-dependent antioxidative stress-protective effect, which is manifested in suppression of the hyperproduction of free radicals and depression of the content of malonic dialdehyde (a secondary product of lipid peroxidation) in the brain of stressed animals. The maximum antioxidative stress protection effect under the conditions of acute and long combined stress has been observed for lithium salt ofcomenic acid in a dose of 2 mg/kg. PMID- 24228482 TI - [Cerebrovascular effects of GABA-prostaglandin E2 conjugate in comparison with prostaglandin E2]. AB - Experiments have shown that GABA conjugate with prostaglandin E2 enhances cerebral blood flow in rats after global transient ischemia, while not affecting the cerebral hemoperfusion in intact animals. It is established that cerebrovascular activity of the GABA conjugate with prostaglandin E2 under conditions of cerebral ischemia is based on GABAergic mechanisms of vascular tone regulation, since it is removed by GABA(A)-receptor blocker bicuculline. At the same time, cerebral blood flow of intact rats and rats after global transient ischemia of brain is equally enhanced by prostaglandin E2 alone. This effect is not neutralized by bicuculline. PMID- 24228483 TI - [Cardioprotective properties of zoniporide studied on experimental ischemia and reperfusion models in rat myocardium]. AB - Using the experimental model of rat heart ischemia/reperfusion, it is established that zoniporide (inhibitor of Na+/H+ exchanger) produces a significant (1.4-fold) decrease in the area of myocardial necrosis, 2.1-fold decrease in the serum troponin I level, and 2-fold decrease in the severity of post-reperfusion arrhythmias. PMID- 24228484 TI - [Search for new drugs with antiarrhythmic properties among derivatives of adamant 2-ylamides of alkylamidocarbonic acids]. AB - The experiments on white outbred awaken male rats have shown that derivatives of adamant-2-ylamides of alkylamidocarbonic acids exhibit prominent antiarrhythmic (antifibrillatory) effect on the model of calcium chloride arrhythmia. The most pronounced effect was demonstrated by N-[2(adamant-2-yl)aminocarbonylmethyl]-N' [3-(diethylamino)propyl]-4-nitrobenzamide. This compound was also active on the model of aconitine arrhythmia, which is characteristic of class-I antiarrhythmic agents. It is established that N-[2-(adamant-2-yl)aminocarbonylmethyl]-N'-[3 (diethylamino)propyl]-4-nitrobenzamide has prominent antiarrhythmic activity and is more safe than other antiarrhythmic drugs of class I (lidocaine, ethmosine, novocainamide), class IV (verapamil), and class III (cardiocyclide). PMID- 24228485 TI - [NO-dependent mechanisms of cardioprotective activity of MT preparation during course administration to SHR rats]. AB - Chronic (15 days) single daily intraperitoneal insertion of the new preparation MT (5 mg/kg) and metoprolol (10 mg/kg) into SHR rats leads to the same decrease (18%) in arterial pressure. In addition, MT exhibits a cardioprotective effect because of NO-mimetic properties, increasing NO formation in myocardium via increasing general NOS activity and eNOS expression. MT normalizes iNOS expression in myocardium mitochondria and decreases nitrotyrosine (nitrosation stress marker) formation. At the same time, the reference preparation metoprolol did not exhibit NO-mimetic properties in myocardium of SHR rats. PMID- 24228486 TI - [Effect of a complex preparation of sea urchin shells on blood glucose level and oxidative stress parameters in type II diabetes model]. AB - The experimental preclinical study on mice showed that a complex of polyhydroxylated naphthoquinone pigments and minerals from shells of sea urchins decreases the concentration of glucose, stimulates the synthesis of phospholipids in liver, and has antioxidant properties. On the model of streptozotocin nicotinamide-induced type II diabetes, this complex of polyhydroxylated naphthoquinone pigments and minerals from sea urchin shells exhibited activity after administration for 10 days in a dose of 1.8 mg/kg. PMID- 24228487 TI - [Assessment of the effects of chronic administration of zinc aspartate and zinc sulfate on amino acid metabolism indicators in tissues and the morphology of small intestine in young rats]. AB - Enteral administration (every day, 10 times) of zinc aspartate (33 mg/kg) or zinc sulfate (25 mg/kg) to young rats weighing 50 - 60 g induces an amino acid imbalance in the blood plasma, liver, and myocardium. Zinc sulfate causes much more pronounced changes in the amino acid balance in the liver and myocardium, as compared to that in rats treated with zinc aspartate. One possible mechanism of the above changes can be the effect of zinc salts on nutrient absorption processes and metabolic features of zinc cations in the small intestine. PMID- 24228488 TI - [Disturbances of the immune status during chronic intoxication with 1,2 dichloroethane and their treatment by administration of polyoxidonium]. AB - It has been established in experiments on noninbred rats that chronic intoxication with 1,2-dichloroethane (30 days; total dose 0.9LD50; daily dose 0.03 mg/kg body weight) causes a reduction of immune responses, decreases the activity of acetylcholinesterase (AChE) of T-lymphocytes, reduces the concentration of blood cytokines (IFN-gamma, IL-2, IL-4, IL-6, while not affecting the content of IL-10), and damages to a greater degree Th1 cells as compared to Th2 lymphocytes. The administration of polyoxidonium (daily dose, 150 mg/kg, for 7 days,) partially restored the immune status, the activity of AChE T cells, and the content of cytokines in the blood. PMID- 24228489 TI - [Potential cytostatic effect of the maleimide derivative 1-(4-Cl-benzyl)-3-Cl-4 (CF3-phenylamino)-1-H-pyrrol-2,5-dione]. AB - The cytostatic/cytotoxic effects of the maleimide derivative 1-(4-Cl-Benzyl)-3-Cl 4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) have been estimated on epithelial derived human cell cultures (Colo 205, MCF-7, and Hela). The anticancer and toxic effects of MI-1 have been investigated on DMH-induced cancer development and normal colon morphology in rats. The results showed that the compound studied has low cytotoxicity but produces a strong antiproliferative effect on cell cultures and partially suppresses colon cancer development in DMH-induced model. The MI-1 effect on normal colon mucosa is insignificant, and no destructive changes have been detected in the intestine of rats. This maleimide derivate can be considered as a promising anticancer drug. PMID- 24228490 TI - [Pharmacological treatment of hemorheological disorders in children with acute respiratory viral infection]. AB - This article presents the results of monitoring in a group of children with severe forms of acute respiratory viral infection and toxic encephalopathy. Hemorheological disorder in the form of hyperviscosity syndrome has been detected in all patients with severe forms of acute respiratory viral infection. It was suggested the inclusion of cytoflavin in the complex therapy for correcting the hemorheological status. The administration of cytoflavin led to reduction of erythrocyte aggregation and general improvements in rheological indices of children with severe forms of acute respiratory viral infection and toxic encephalopathy. PMID- 24228491 TI - [Comparative analysis of the effectiveness of antiviral therapy of children with infectious mononucleosis]. AB - A group of 126 children (4 to 7 years old) with infectious mononucleosis received basic therapy in combination with nonspecific antiviral drugs. The same therapeutic efficiency was observed for cycloferon and genferon light included in complex treatment of infectious mononucleosis in children. The use of cycloferon (10 mg/kg i.m., single daily injection for 10 days) prevents the development of frequent acute respiratory viral infections in the period of convalescence. PMID- 24228492 TI - [Association of microsatellite loci alleles of the group-5 chromosomes with frost resistance of winter wheat]. AB - Analysis of frost resistance and microsatellite analysis of the group-5 chromosomes were performed on parental varieties and recombinant-inbred lines F7 Luzanovka odesskaya/Odesskaya krasnokolosaya. Allelic differences for Xcfd7-5B Xwmc415-5B and Xgwm 182-5D microsatellite loci were associated with the level of frost resistance of the lines. PMID- 24228493 TI - [Putative temperature sensitive riboswitchers in Salmonella genome]. AB - Currently, a number of structurally and functionally different temperature sensitive elements like as RNA thermometers which control a variety of biological processes of bacteria, including virulence, are known. Well-known RNA thermometers correspond to one long step-loop structure or few hairpins which can be matched or mismatched. Based on the computer and thermodynamical analysis of 25 isolates of Salmonella enterica with complete genome, algorithm and the criteria of search for putative RNA thermometers were developed. It will permit to perform the search of potential riboswitchers in genome of socially significant pathogens in the future. For S. enterica, in addition to well-known 4U RNA thermometer, four step-loop structures that may be new RNA thermometers were identified and two of them are localized in 5'-UTR of virulence regulators gltB and yaeQ. They correspond to necessary and sufficient conditions of RNA thermometer formation as far as these highly conservative structures are found in genome of all 25 isolates of S. enterica. Matched hairpins forming cruciform structure in supercoiled pUC8 plasmid were visualized by atomic force microscopy. PMID- 24228494 TI - The association between GAD1 gene polymorphisms and cerebral palsy in Chinese infants. AB - Studies suggest that GAD1 gene was a functional candidate susceptibility gene for cerebral palsy (CP). In order to investigate the contribution of GAD1 gene to the etiology of CP in Chinese infants, we carried out a case-control association study between GAD1 gene and CP. In this study, 374 health controls and 392 infants with CP were recruited. Genomic DNA was extracted from venous blood and all three single nucleotide polymorphisms in GAD1 (rs3791874, rs3791862 and rs16858977) were genotyped by Sequenom's MassARRAY system. There were no significant differences in allele or genotype frequencies between CP or mixed CP patients and controls at any of the three genetic polymorphisms. Through haplotype analysis we found that haplotype GG (rs3791862, rs16858977) frequency demonstrated significantly statistical difference between mixed CP patients and controls (p = 0.0371). Our positive findings of haplotype GG suggested that variation of GAD1 gene was an important risk factor for mixed CP. PMID- 24228495 TI - Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta. AB - Dentinogenesis imperfecta Type II (DGI-II) is a condition inherited as an autosomal dominant trait and characterized by abnormal dentine structure affecting both the primary and secondary dentitions. The genetic etiology of the disease still remains unclear, suggesting a genetically heterogeneous background. The aim of this study is to manifest briefly DGI-II and to investigate the association between BsmI, TaqI and FokI polymorphisms of Vitamin D receptor (VDR) gene and dentinogenesis imperfecta type II in a Turkish family by PCR-RFLP methodology. The affected mother and her two affected daughters were bb for BsmI polymorphism, whereas her unaffected son and her husband were Bb for the same polymorphism. One of the affected children was tt, the rest of the family were Tt for TaqI polymorphism, and all of the enrolled subjects were FF for FokI polymorphism. As a conclusion, BsmI polymorphism bb seems to be associated with (DGI-II), but should be examined in larger numbers in order to be considered as a risk factor. PMID- 24228496 TI - [Analysis of matrix Gla-protein (MGP) G-7A polymorphism association with ischemic atherothrombotic stroke in persons with risk factors]. AB - G-7A polymorphism (rs1800801) of matrix Gla protein (MGP) gene in 170 patients with ischemic atherothrombotic stroke (IATS) and in 124 persons of the control group was determined. It was shown that in patients with IATS the distribution of the major allele homozygotes, heterozygotes and minor allele homozygotes was 35.9; 48.8; 15.3% (in control--43.5; 50.0; 6.5%, P = 0.051 by chi2-test). Significant differences in the distribution of genotypes were revealed only in women (P = 0.022). Odds ratio for minor allele homozygotes (A/A) versus major allele carriers (G/A+G/G) was 2,618 (P = 0.023), while in women it was equal to 6,645 (P = 0.015). In patients with A/A genotype the values of blood coagulation parameters (prothrombin time) indicated increased predisposition to hypercoagulability. The results obtained suggest that the A/A-variant of MGP gene is associated with an increased risk of IATS in female persons of the Ukrainian population and may be related to blood hypercoagulability and thrombi formation. PMID- 24228497 TI - [Allelic state of the molecular marker for the golden nematode (Globodera rostochiensis) resistance gene H1 among Ukrainian and world cultivars of potato (Solanum tuberosum ssp. tuberosum)]. AB - The purpose of our investigation was determination of allelic state of the H1 resistance gene against the pathotypes Ro1 and Ro4 of golden potato cyst nematode (Globodera rostochiensis) among Ukrainian and world potato (Solanum tuberosum ssp. tuberosum) cultivars. The allelic condition of the TG689 marker was determined by PCR with DNA samples isolated from tubers of potato and primers, one pair of which flanks the allele-specific region and the other one was used for the control of DNA quality. Among analyzed 77 potato cultivars the allele of marker associated with the H1-type resistance was found in 74% of Ukrainian and 90% foreign ones although some of those cultivars proved to be susceptible to the golden potato nematode in field. The obtained data confirm the presence of H1 resistance against golden nematode pathotypes Ro1 and Ro4 among the Ukrainian potato cultivars and efficiency of the used marker within the accuracy that has been declared by its authors. PMID- 24228498 TI - [Ultrastructure and pigment composition of Sagittaria sagittifolia L. leaves]. AB - Comparative analysis of the cellular ultrastructure and pigment content of both submerged and above-water Sagittaria sagittifolia leaves with transmission electron microscopic and biochemical methods were realized. Essential distinctions of S. sagittifolia ultrastructure of photosynthesizing cells in submerged leaves were revealed during the comparison with those in mesophyll cells of above-water leaves. The changes of chloroplast ultrastructure in submerged leaves are examined as the adaptative signs of photosynthesizing cells under influence of altered environment. PMID- 24228499 TI - Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages. AB - Hypoxia is an important factor in the macrophages microenvironment. Many physiological and pathological processes including solid tumor development are characterized by both low oxygen content and presence of macrophages. Tumor associated hypoxia causes alternative polarization of macrophages in tumor tissue and transformation of these cells into the allies of a malignant neoplasm. The aim of the work was to investigate the effect of NSC631570, a cancer-selective drug that is known to selectively accumulate in the tumor tissue, on hypoxic macrophage function. Murine peritoneal macrophages (PMs) were subjected to hypoxia (3% O2). Nitrite level was assayed by the Griess reaction. Arginase activity was measured by colorimetric method. ROS generation and phagocytosis was estimated by flow cytometry. O2(-) generation was assayed by the NBT reduction method. HMGB1 expression was determined by ELISA. 42 h hypoxia caused alternative polarization of murine PMs with significant arginase prevalence. NSC631570 repolarized arginine metabolism of hypoxic macrophages to NOS dominant and activated their pro-inflammatory functions: recovered ROS production and increased alarmin release NSC631570 can restore pro-inflammatory functions of macrophages, alternatively polarized by hypoxia. PMID- 24228500 TI - [Orbicular oris muscle flap wrapped by acellular dermis for the treatment of upper lip atrophy in children]. AB - OBJECTIVE: To investigate the treatment of upper lip atrophy resulted by previous therapy. METHODS: From Mar. 2008 to Mar. 2012, 4 cases with upper lip atrophy resulted by radiotherapy and sclerosing agent injection were treated with lower orbicularis oris muscle flap wrapped by acellular dermis. The thickness and height of upper lip were increased to improve the lip atrophy. RESULTS: Primary wound healing was achieved in all the 4 cases. All the patients were followed up for 3 years with obvious improvement and inconspicuous scar. CONCLUSION: The volume of lower lip in children is not sufficient as donor site. The lower orbicularis oris muscle flap wrapped by acellular dermis can effectively improve the lip thickness and vermilion portion of upper lip. PMID- 24228501 TI - [Correction of shortened and broaden prolabium deformity with double flag-shaped flaps following bilateral cleft lip repair]. AB - OBJECTIVE: To explore the correction for shortened and broaden prolabium deformity following bilateral cleft lip repair. METHODS: We designed the upper lip double flag-shaped flaps. The quadrilateral original surgical scar (flap flag pole part) was resected and the incision was made along the direction of nasolabial groove at the nostrils bottom to form two flag-shaped flaps (the section of the flag face). Lip tubercle were tracted and blunt dissection of upper philtrum were performed to form a wound, 4-6 mm in width. The flag-shaped flaps on both sides were rotated to the central, in order to form a new nasal base and new prolabium, followed by V-Y or Z plasty procedure to correct the defect of tubercle and vermilion. RESULTS: 10 cases were enrolled for the clinical application from January 2008 to December 2012. The height of the prolabium was lengthened by 4-6 mm after operation, which fundamentally corrected shortened and broaden prolabium deformity after bilateral cleft lip operation. The procedure can also correct the depression or defect of tubercle, too wide philtrum, philtrum column scar and the deformity of vermilion border continuity. The patients were followed up for a period of 3 months to 3 years with satisfactory results. CONCLUSION: Double flag-shaped flaps of the upper lip at the nostrils bottom is a simple and good surgery method to correct the shortened and broaden prolabium deformity following bilateral cleft lip repair. PMID- 24228502 TI - [The application of composite skin-vermilion triangle fap and functional reposition of orbicularis muscle in congenital cleft lip]. AB - OBJECTIVE: To investigate the ideal method for correction of vermilion deformity in congenital cleft lip. METHODS: From Mar. 2010 to Jan. 2013, 68 cases with congenital cleft lip underwent vermilion deformities correction with composite skin-vermilion triangle fap and functional reposition of orbicularis oris muscle. RESULTS: Primary healing was achieved in all the patients. 46 cases were followed up for 3 months to one year. Asymmetric thickness of vermilion and tubercle malposition happened in 8 cases. All the other patients had a satisfactory result with symmetric and fluent cupid' s bow and everting tubercle. CONCLUSION: Well reposition of orbicularis oris muscle is key for correction of vermilion deformity and tubercle reconstruction. This technique is very simple and practical. PMID- 24228503 TI - [The application of pedicle orbital fat flap for the correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people]. AB - OBJECTIVE: To explore the effective techniques for correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people. METHOD: The lacrimal groove and palpebromalar groove deformity was corrected by the techniques of transcutaneous orbital fat releasing and pedicle orbital fat flap filling. From 1996 to 2011, 426 patients, aged from 35 to 72 (average, 48), were treated by the techniques. Among them, 54 patients had underwent the surgical treatment before this operation. 362 patients were followed up for 3-24 months. RESULTS: Completely correction was achieved in 283 patients, obvious improvement in 79 patients. The result was not satisfied in 2 patients with severe deformity who had surgical treatment before. CONCLUSION: The lacrimal groove and palpebromalar groove deformity can be effectively corrected by transcutaneous orbital fat releasing and pedicle orbital fat flap in the middle-aged and old people. PMID- 24228504 TI - [Effect of vacuum drainage on the blood circulation of expanded flap in ear reconstruction]. AB - OBJECTIVE: To investigate the effect of vacuum drainage on blood circulation of expanded skin flap, so as to confirm suitable negative pressure for ear reconstruction. METHODS: 21 patients (Auricular Reconstructive Center of Plastic Surgery Hospital, PUMC) were randomly divided into A, B, C 3 groups to receive vacuum drainage of: -20, -40 and -60 kPa, respectively. The length and width of reconstructed ears,which represented the swelling degree, were measured instantly and 5, 10 days postoperatively. The changes were calculated and reflected venous drainage of flaps. The temperature of proximal (concha) and distal (helix) part of the expanded flaps, which represented the arterial blood supply of flaps, was detected by infrared thermography after operation. RESULTS: Five days after operation [(1.48 +/- 0.47) mm, (0.36 +/- 0.06) mm] and immediately [(1.67 +/- 0.69) mm, (0.40 +/- 0.16) mm)] , the changes of the length and width of reconstructed ear in group B was significantly low, while there was no statistically difference between group A and C (P > 0.05). The data between 10 days and 5 days after operation showed the same result. Along with the increase of the negative pressure, the swelling degree of reconstructed ears decreased firstly and then increased reversely ( P < 0.01 ). The flap temperature of reconstructed ears increased (P < 0.01), especially in proximal (concha) part (P < 0.01) , when the negative pressure increased (0 to -60 kPa). CONCLUSIONS: Vacuum drainage has effect on both the venous drainage and blood supply. Negative pressure of -40 kPa can improve both the blood supply and venous drainage. It should be as reference for clinical application. PMID- 24228505 TI - [Vacuum sealing drainage and free coupling chain-link posterior tibial artery flap in the reconstruction of degloving injury of propodium]. AB - OBJECTIVE: To present the methods of vacuum sealing drainage and free coupling chain-link flap of posterior tibial artery flap and medial plantar flap in the reconstruction of degloving injury of propodium. METHODS: From Oct. 2008 to Dec. 2011 five cases with degloving injury of propodium underwent debridement and vacuum sealing drainage on the first stage. Free chain-link flap of posterior tibial artery flap and medial plantar flap were applied to close the wound at the secondary stage. The nerve was included in the coupling flaps. The size of posterior tibial artery flap ranged from 14 cm x 10 cm to 11 cm x 8 cm,and the size of medial plantar flap ranged from 12 cm x 8 cm to 8 cm x 6 cm. RESULTS: All flaps were survived with no vascular crisis. The flap sensation recovered to S3 S3 during the follow-up period of 6-21 months. The texture and appearance of flaps were satisfied. The plantar had not ulcer and corpus callosum. CONCLUSION: Vacuum sealing drainage and free chain-link flap of posterior tibial artery flap and medial plantar flap with nerve are the ideal methods for the reconstruction of degloving injury of propodium. PMID- 24228506 TI - [Anatomic study and clinical application of thinned posterior tibial artery perforator flap]. AB - OBJECTIVE: To explore the feasibility and therapeutic effect of thinned posterior tibial artery free perforator flap for the reconstruction of soft tissue defects at dorsum of hands. METHODS: Six fresh adult lower limbs specimens were injected with red latex via arterial cannula and dissected. The number, distribution, branches, and outer diameter of posterior tibia artery perforators were observed. Based on the anatomic study, the perforator flaps were designed to reconstruct soft tissue defects at dorsum of hands and wrists. The redundant fat on the flaps was removed, but preserving the nutrient vascular system. 11 flaps were used with the size ranging from 2 cm x 5 cm to 10 cm x 14 cm. RESULTS: 43 skin perforators of posterior tibial artery were observed in six lower limbs, 29 perforators with the outer diameter is greater than 0.5 mm when they threading over the deep fascia plane, on average every 4.8 bundles of sides. The mean outside diameter of perforating artery is (1.8 +/- 0.5) mm, and the length is (44 +/- 15) mm. 6 perforators were founded both in the second and fifth zone which could be used for anastomosis for its better diameters. All flaps survived completely without any complication at donor sites. 7 cases were followed up for 3-12 months. Both satisfactory functional and cosmetic results were achieved with a soft and thinned appearance. CONCLUSIONS: The thinned posterior tibial artery free perforator flap has a reliable blood supply and good appearance. It is very suitable for the reconstruction of small or medium-sized defects at the dorsum of hands and wrists. PMID- 24228507 TI - [Lux1540nm fractional laser treatment for superficial scar]. AB - OBJECTIVE: To observe the effect of non-ablative fractional laser Lux1540nm in superficial scars therapy. METHODS: According to the Fitzpatrik skin type and scar appearances, appropriate laser energy and pulse width were selected for scar treatment. Therapeutic effect and side-effect was evaluated by preoperative photos and 6 months of postoperative photos. RESULTS: The total effective rate was 78.12% (28/32). 7 cases (21.88%) showed ineffective results. The therapeutic effect was improved along the increase of treatments. Temporary hyperpigmentation was found in 3 cases (9.38%) and faded away within 3-6 months. Temporary erythema faded away within 4-24 hours. CONCLUSION: The treatment of non-ablative fractional laser Lux1540nm for superficial scar is effective with minimum side effect. PMID- 24228508 TI - [Connective tissue growth factor induced differentiation of placenta mesenchymal stem cell into dermal fibroblast]. AB - OBJECTIVE: To investigate the possibility of placenta mesenchymal stem cells (PMSCs) differentiation into dermal fibroblast, and the potency of PMSCs used in cutaneous wound healing and stored as seed cells. METHODS: Enzyme digestion method was used to obtain PMSCs, and PMSCs were amplified after culture in vitro. Flow cytometry assay, osteogenic and adipogenic differentiation were done for MSCs identification. The induction medium composed of DMEM/F12 + 50 microg/ml VC + 100 ng/ml connective tissue growth factor (CTGF) was added into the 24-well plate for 16 days induction period. Pictures were taken to record morphologic change. Immunofluorescence tests were performed to detect Vimentin, FSP-1, collagen I , collagen III, desmin and laminin expression before and after induction. At the same time osteogenic and adipogenic differentiation were used to assay the differentiation ability change after induction. The induced dermal fibroblasts were frozen in liquid nitrogen and recovery and trypan blue was used to detect cell viability. RESULTS: After CTGF induction, PMSCs got obvious fibroblasts morphology, the protein level of Vimentin, FSP-1, collagen I, collagen III and Laminin increased, PMSCs started to express Desmin, the dermal fibroblasts specific proteins, and osteogenic and adipogenic differentiation ability was diminished. PMSCs were successfully induced into dermal fibroblasts, and these induced cells could get a high cell viability ( more than 90% ) after recovery. CONCLUSIONS: PMSCs could be induced into dermal fibroblasts by CTGF in vitro. PMSCs have the potential application in skin wound healing, and can be used as seed cells of dermal fibroblasts. PMID- 24228509 TI - [The research of fibroblasts from human hypertrophic scar showing a mesenchymal stem cell phenotype and multilineage differentiation potentialities]. AB - OBJECTIVE: To explore the CD phenotypic, protein expression and pluripotent differentiation of human hypertrophic scar fibroblasts cultured in vitro, so as to study the mechanisms of scar formation. METHODS: Fibroblasts were isolated and cultured from human hypertrophic scar of 3 cases. The cells morphology was observed by inverted microscope, and the growing state of the third passage was detected by the cell counting meter of Vi-CELL. The cell surface markers CD105, CD14, CD73, CD34, CD44, CD45 and CD90 were identified by flow cytometry. The expression of CK19, Oct-4, Nanog and vimentin was detected by immunocytochemistry, and the expression of alpha-smooth muscle actin(alpha-SMA) was tested by immunofluorescence. The differentiated potential of fibroblasts of the third passage into adipogenic, osteogenic and chondrogenic lineages was assayed. RESULTS: The primary passage fibroblasts showed the shape of spindle shaped or irregular polygon with a radiated or circinate of growing arrangement. The growth curve showed the cells growth was slow on the first and second day, and quick during the third to fifth day, which reached platform stage on the sixth or seventh day. The fibroblasts highly expressed mesenchymal stem cell surface markers-CD73, CD105, CD44, CD90, but not expressed hematopoietic stem cell surface markers-CD14, CD34, CD45 by flow cytometry. And positive expression of vimentin, Oct-4 and negative expression of CK19 were detected by Immunocytochemistry. Positive expression of alpha-SMA was also detected by immunofluorescence. Multidirectional differentiation induction indicated that the third passage cells could differentiate into adipogenic, osteogenic and chondrogenic lineages. CONCLUSIONS: Human hypertrophic scar-derived fibroblasts show the biologic characteristics of mesenchymal stem cells, which may play an important role in wound healing and hypertrophic scar formation. PMID- 24228510 TI - [Identification of differently expressed microRNAs in keloid and pilot study on biological function of miR-199a-5p]. AB - OBJECTIVE: To screen out related microRNAs in keloid tissue, and identify their effect on the proliferation of keloid fibroblasts. METHODS: 8 cases of keloid tissue and 8 cases of normal skin tissue were collected as specimens. The differently expressed miRNA in keloid tissue from normal skin tissue were screened out with gene chip( Exiqon company), which was validated with quantitative real-time PCR. Then miRNA mimics was transfected into keloid fibroblasts line to stimulate high expression of mature miRNA in cells. The effect on the proliferation of fibroblasts in keloid was tested by Edu. RESULTS: (1) A total of 17 differently expressed microRNAs were found, including miR-199a 5p. (2) The expression of miR-199a-5p had been verified by qRT-PCR to be down regulated in keloid, which was consistent with the result of array. (3) The positive rate of EdU in miR-199a-5p mimics transfected group and negative control group was (20.72 +/- 2.50)% and (27.68 +/- 4.92)%, respectively. The proliferative rate of keloid fibroblasts turned down in miR-199a-5p-transfected group (t = 2.183, P = 0.047). Besides that, the cell cycle changed after transfection. The percentage of S and G2/M phase in miR-199a-5p mimics transfected group was 33.93 +/- 1.30 and 10.87 +/- 0.80, respectively, while it was 31.39 +/- 0.79 and 9.27 +/- 0.46 in negative control group, and the difference was statistically significant. CONCLUSIONS: (1) The miRNA expression profile is different between keloid and normal skin; (2) The expression of miR 199a-5p is down-regulated in keloid and miR-199a-5p can affect the cell cycle and suppress proliferation of keloid fibroblasts. It indicateds that miR-199a-5p may be involved in regulating fibroblastic proliferation. PMID- 24228511 TI - [Effect of the methylation enzyme inhibitors of 5-aza-2-deoxycytidine on the TGF beta/smad signal transduction pathway in human keloid fibroblasts]. AB - OBJECTIVE: To investigate the effect of 5-aza-2-deoxycytidine on the TGF beta/smad signal transduction pathway in human keloid fibroblasts (KFSs). METHODS: Firstly, immunohistochemical method was used to detect the positive expression rate of phospho-smad2 and phospho-smad3 in the specimens of 15 cases of keloid and 15 cases of normal skin. The keloid fibroblasts were cultured in vitro with 5-aza-2-deoxycytidine(experimental group) or with DMEM (control group). The effect of 5-aza-2-deoxycytidine on the cell cycle and apoptosis of fibroblasts was analysed with flow cytometry ( FCM). Transforming growth factor (TGF)-beta1, Smad7, phospho-smad2 and phospho-smad3 were analyzed by Western Blot, and Immunofluorescence. RESULTS: It was found that the positive expression of phospho-smad2 and phospho-smad3 in keloid were higher than those in normal skin. The FCM showed that the proportion of cells in G0/G1 stage was increased, and so does the proportion of apoptosis cells in keloid fibroblasts intervened by 5-aza-2-deoxycytidine. The expression of TGF-beta1, phospho-smad2 and phospho smad3 protein were significantly suppressed while the expression of smad7 protein increased in keloid fibroblasts with 5-aza-2-deoxycytidine. In addition, 5-aza-2 deoxycytidine reversed phosphorylation and nuclear translocation of smad2 and smad3. CONCLUSIONS: 5-aza-2-deoxycytidine, methylase inhibitors, inhibits cell proliferation and promotes apoptosis of KFSs, which may be associated with the suppression of TGF-beta/smad signal pathway. PMID- 24228512 TI - [The significance of beta-receptor expression in infantile hemangiomas]. AB - OBJECTIVE: To investigate the expression and significance of beta-receptor ( p-R) in infantile hemangioma. METHODS: The expression of beta-R was detected by immunohistochemistry in infantile hemangioma (40 cases), venous malformation (20 cases) and normal skin (10 cases). RESULTS: The positive expression rate of beta2 R was 70% (28/40) in infantile hemangioma, while no expression of beta2-R in venous malformation and normal skin. Among 28 cases with positive expression of beta2-R, 24 cases were in proliferative phase. The positive expression of beta2-R in infantile hemangioma was significantly higher than that in venous malformation and normal skin tissue. The positive expression of beta2-R in the proliferative hemangioma and non-proliferative hemangioma was also significantly different (P < 0.05). CONCLUSIONS: beta2-R is specifically expressed in infantile hemangioma, especially in proliferative hemangioma. PMID- 24228513 TI - [Endoplasmic reticulum-mediated integrated stress response]. AB - Integrated stress response (ISR) is a high conserved cell adaptive response, which is induced by oxidative stress, deprivation of acid aminos, and endoplasmic reticulum (ER) stress through eukaryotic translation initiator factor 2alpha (eIF2alpha) pathway. Recently, it is reported that protein kinase R-like ER kinase (PERK) , the upstream of eIF2alpha is the key molecule in ISR. PERK regulates protein synthesis, folding, autophagy and apoptosis through cross talking with inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6), another two signaling pathways in ER stress. We reviewed the factors induced ISR and its signaling pathways, summarized the physiological and pathophysiological role of endoplasmic reticulum-mediated integrated stress response. PMID- 24228514 TI - [Research progress in pathogenesis of IBD: the role of gut flora]. AB - Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the intestine. Both the etiology and the pathogenesis of IBD remain unclear. In recent years, the role of gut flora in IBD has become one of the most concerned issues. International metagenomic projects targeting the gut microbiota greatly promote the exploration of the role of gut flora in IBD. What are the characteristics of gut flora in IBD? How does it interact with host susceptibility? This review will discuss the enteric dysbacteriosis in IBD and show the interaction between gut flora, especially the dominant gut flora, and host susceptibility in IBD. PMID- 24228515 TI - [Multiple mechanisms of depression]. AB - Depression is a grievous mental disease with an increasing high morbidity year by year and a serious social harm. The pathogenesises of depression is complicated and involves with multi-mechanisms and multi-organs. Recent studies demondtrate that in the nerval system and endocrine system there are many types of neurotransmitters and hormones, as well as their receptors, involved in depression. This paper reviews the research progress of depression in recent years. PMID- 24228516 TI - [Role of toll-like receptor 2 in cardiovascular diseases]. AB - Toll-like receptors are the important pattern recognition receptors of innate immune system, which mediate the immunological defence response against pathogen or endogenous damage associated molecules. Recently, more and more researches indicated that Toll-like receptor 2 played vital roles in the pathophysiology of many cardiovascular diseases, including atherosclerosis, coronary diseases, cardiac ischemia-reperfusion injury. In the current report, we review the research progress on the role of Toll-like Receptor 2 in cardiovascular diseases. PMID- 24228517 TI - [Research advance of large conductance Ca(2+)-activated K+ channels in cardiovascular system]. AB - The large conductance Ca(2+)-activated potassium channels (BK(Ca) channels), an important class of ion channels in cell membrane, are widely expressed in each part of the body including cardiovascular system, and play an important role in regulating cardiovascular activity. This review introduces the recent progress on the structural features, function, and modulation of BK(Ca) channels in cardiovascular system briefly. PMID- 24228518 TI - [Role of Rho/ROCK in the migration of vascular smooth muscle cells]. AB - The migration of vascular smooth muscle cells (VSMCs) from media to intima is a critical step in the formation of atheroma and vascular stenosis as well as in the restenosis after vascular intervention. As an important downstream effector of RhoA, Rho-associated kinase (ROCK) plays an important role in VSMC migration and vascular remodeling by regulating actin filament cytoskeleton and focal adhesion. There are many bioactive substances such as aldosterone, sphingosine 1 phosphate (S1P), platelet-derived growth factor (PDGF) and angiotensin II (Ang II) that could induce VSMC migration through Rho/ROCK pathway by binding to their specific receptors. Studies on Rho/ROCK pathway could help us to better understand how cardiovascular diseases such as atherosclerosis and hypertension develop. PMID- 24228519 TI - [Exercise intervention in skeletal muscle endocrine function]. AB - As a new secretory organ skeletal muscle, which could secrete a variety of biological active substances, plays an important role in biological function and clinical medicine, and has important research value and application scenarios in the field of sports medicine. Different mode and intensity of exercise would give different influences on skeletal muscle endocrine function. Exercise intervention could improve the chronic disease, such as metabolic disease (obesity, diabetes) and muscle atrophy by changing endocrine function of the skeletal muscle. It will be great valuable to explore the mechanisms of exercise-induced skeletal muscle endocrine, seek for the appropriate biomarker, make exercise prescription, which would give improtant theoretical value and application prospect for the exercise system function improvement metabolic disease grevention and exercise rehabilitation of the systemic diseases. PMID- 24228520 TI - [Necroptosis: a programmed cell necrosis]. AB - Cell death is one of the basic life properties. A new type of cell death named necroptosis was discovered and became increasingly noticed attention in recent years. Necroptosis has similar morphological characteristics with cell necrosis and is controlled by special signal pathways. The interaction of the receptor interacting protein 1 (RIP1) and 3 (RIP3) plays a crucial important role in the necroptosis signal pathway. The RIP1 determines whether a cell goes survival and death, and the RIP3 determines the pathway of cell death apoptosis or necrosis. This paper summarizes the knowledge about the necroptosis signal pathways and explores its significance in the organ ischemic injury, inflammation and tumor pathogenesis briefly. PMID- 24228521 TI - [Sumoylation regulates nuclear receptor function]. PMID- 24228522 TI - [The structure characteristics, biology functions and underlying mechanisms of GPR120]. PMID- 24228523 TI - [Research progress of EETs in cardiovascular disease homeostasis]. PMID- 24228524 TI - [Interleukin-17 receptor C]. PMID- 24228525 TI - [The role of sirt1 in kidney diseases]. PMID- 24228526 TI - [The regulation of hematopoietic stem cells by mononuclear phagocyte system in bone marrow]. PMID- 24228527 TI - [The pioneer in study of nerve impulses--Andrew Fielding Huxley]. PMID- 24228528 TI - [Study of drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution]. AB - OBJECTIVE: To discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution. METHOD: PBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size. RESULT: Compared with the normal group, there appeared some single or oligoclonal amplification of Vbeta CDR3 region in the patients, which were improved or recovered after treatment. Among them, D value of four families (9, 11, 21, 22 ) decreased after treatment in both groups. The decrease in family 21 and 22 was significant (P < 0.05) in treatment group compared with the control group. And family 18 was decreased in treatment group and increased significantly in control group (P < 0.05). CONCLUSION: Study of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T-cell apoptosis. PMID- 24228529 TI - [Correlation study of HIV/AIDS abnormal immune activation and disease progression]. AB - OBJECTIVE: To learn the levels of immune function and immune activation of HIV/AIDS patients in China and find the correlation between the immune activation and CD4+ T lymphocyte and disease progression. And discuss the relevance of immune activation with HIV/AIDS pathogenesis. METHOD: Two hundred and eighty seven cases of HIV/AIDS patients in different disease stages who never accept HAART before and 40 healthy HIV negative donors have been involved in the research. Their immune function and abnormal immune activation markers are detected by flow cytometry counts, and the immune activation markers include CD8 CD38+ T cells and CD8+ HLA-DR+ T cell. Compare the difference of abnormal immune activation between patients of various disease stages. And by Pearson correlation test analysis, the correlation between the immune activation levels and abnormal CD4+ T lymphocyte count and disease progression will be found. RESULT: The immune abnormal activation levels were significantly different between patients of different disease stages (P < 0.001). Correlation analysis showed that there was a significant negative correlation between peripheral blood CD4+ T cell counts and immune activation markers. CONCLUSION: Immune activation induced by HIV infection may lead to decreased CD4+ T cell count and disease progression. PMID- 24228530 TI - [Spectrum-effect relationship between anti-HIV 1 activities and ultra-performance liquid chromatography fingerprints of Rheum species]. AB - OBJECTIVE: To study the relationship between ultra-performance liquid chromatography (UPLC) fingerprints of Rheum species and their anti-HIV 1 activities. METHOD: Twenty two samples of 16 species belonging to genus Rheum from various sources were collected and analyzed in this study. Firstly they were assayed for the HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) activity. Secondly the fingerprints were established by an optimized UPLC method. Sample was analyzed by UPLC-TOF-MS/MS to identify major peaks. The possible relationship between UPLC fingerprints and anti-HIV 1 activities of Rheum species were deduced by mathematical statistics method. RESULT: Samples of R. austral, R. austral, R. hotaoense exhibited good anti-HIV 1 activities with IC50 < or = 0.2 mg x L(-1). The correlation of anti-HIV 1 activities and fingerprints showed that three compounds were the main bioactive components, and their retention times were 4.74, 7.99, 21.18 min, respectively. CONCLUSION: Compounds in Rheum species with possible anti-HIV 1 activities were deduced by spectrum-effect relationship study. This study supported for study of medicinal plants in Rheum. PMID- 24228531 TI - [Diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution and influence of drug]. AB - OBJECTIVE: To discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution. METHOD: PBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with Immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size. RESULT: (1) Gaussian distribution of TCRVbeta families in patients with incomplete immune reconstitution after one year of HAART, had been broken with the occurrence of the offset TCR lineage. After six months of treatment of traditional Chinese medicine combined HAART, the TCR lineage has been partially restored. (2) Evaluated by the D (distance) value calculated by a quantitative analysis software which the kit provides, there were no significant difference in D value change between the two groups, but with traditional Chinese medicine can reduce the data variability. (3) CD4+ T cell counts had a significant correlation (r = -0.772, P = 0.000) with TCRVbeta genetic diversity. CONCLUSION: Study of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T-cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T cell apoptosis. PMID- 24228532 TI - [Multi-centered, randomized controlled clinical study on Chinese medicine formula particles for hyperlipidaemia associated with highly active antiretroviral therapy]. AB - OBJECTIVE: To observe the effect and safety of Xiaozhi particles, integrated taohong Siwu tang and Erchen tang and Xuezhikang capsule in treating hyperlipidaemia (HLP) associated with highly active antiretroviral therapy (HAART). METHOD: In the multi-centered, randomized controlled clinical study, 180 hyperlipidaemia associated with highly active antiretroviral therapy cases were divided into the treatment group treated by Xiaozhi particles, integrated Taohong Siwu tang and Erchen tang, and the control group treated by Xuezhikang capsule. The treatment course was 12 weeks. The total cholesterol (Tch), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein(HDL) were observed. RESULT: After 12 weeks, compared with Xuezhikang capsule, the change difference of Tch, LDL, HDL in the Chinese traditional medicine formula groups of patients is significant (P < 0.05), the change of the TG has no significant difference. The effect of Tch, LDL in Xuezhikang capsule groups is better than in traditional Chinese medicine formula group,but the effect of HDL in traditional Chinese medicine formula group is better than in Xuezhikang capsule groups. CONCLUSION: Integrated Taohong Siwu tang and Erchen tang, Xiaozhi particles and Xuezhikang capsule can be used to control the hyperlipidaemia associated with highly active antiretroviral therapy as one of the main Chinese native medicine preparation. PMID- 24228533 TI - [Randomized controlled study of integrated treatment of traditional Chinese medicine and western medicine on AIDS with pulmonary inflammation patients]. AB - OBJECTIVE: To compare effects of integrated treatment traditional Chinese medicine and Western medicine (TCM-WM) and simple western medicine on TCM clincal symptoms in the patient of AIDS with pulmonary inflammation. METHOD: A multicenter randomized controlled trials of 164 subjects evaluated the effects of clinical symptoms of AIDS with pulmonary inflammation of TWO regimens: the TCM-WM group (n = 111) and western medicine treatment group (n = 53), while incidence of TCM symptoms in different time points in two groups were analyzed. RESULT: Twenty eight days after treatment, the cured and markedly effective rate of TCM symptoms in the TCM-WM group significantly exceeding that in the western medicine treatment group (cured and markedly effective rate significant efficiency 44.55% vs 20.00%), while the incidence rate for the TCM symptoms of fever and headache in the TCM-WM group was significantly lower than that in western medicine group. CONCLUSION: The integrated treatment of traditional Chinese medicine and Western medicine helps to alleviate the TCM clinical symptoms of AIDS with pulmonary inflammation. PMID- 24228534 TI - [Intervention of immune 1 combined HAART on immune function in patients with HIV/AIDS reconstruction]. AB - OBJECTIVE: To observe the effect of combination of Immune 1 and HAART on the CD4+ T cell count and its immune reconstitution rate. METHOD: Two hundred and twenty eight HIV/AIDS patients were randomly divided into treatment group and control group, patients from treatment group received Immune 1 combined HAART therapy, patients from control group was given placebo combined HAART and evaluate the change of CD4+ T cell count and its immune reconstitution rate. RESULT: In patients with CD4+ T cells baseline level (200-350 cell x microL(-1)), Immune reconstitution rate of treatment group is significantly higher than the control group. CONCLUSION: Immune 1 combined HAART can effectively promote the immune reconstitution of patients with high CD4+ T cells baseline level(200-350 cell x microL(-1)) and show little side effect and is safe to treat HIV/AIDS disease. PMID- 24228535 TI - [Effect of immune 2 with highly active antiretroviral treatment on immune function of HIV/AIDS patients with poor immune reconstitution]. AB - OBJECTIVE: To observe the effection of immune reconstitution efficiency and the immune function on Immune 2 with HAART to HIV/AIDS patients which poor immune reconstitution after HAART. METHOD: Two hundred and sixty four patients failure to immune reconstitution after HAART were randomly divided into treatment group (131 cases) and control group (133 cases), respectively, using Immune 2 plus HAART and placebo combined with HAART for 6 months. the CD4, CD8, CD45RA, CD45RO, CD4CD28, CD8CD28, CD8CD38, HLA-DR and CD4CD25 were observed in order to evaluate the immune reconstitution efficiency. RESULT: After the intervention for 6 months, the effective rate of treatment group (34.48%) was significantly superior to the control group (21.37%) (P = 0.0217). Treated group could significantly increased the CD4, CD45RA, CD45RO cell counts compared with control group (P < 0.05); CD8, CD3, CD4CD28 absolute count comparison between the two groups had no significant difference; CD8CD28 relative counting the treatment group group significantly increased (P < 0.05) compared to the control; CD4CD28, CD8CD38, CD8DR, CD4CD25 relative counting groups showed no significant difference. CONCLUSION: Immune 2 can effectively improve the immune reconstitution efficiency, CD4 counts, CD45RA counts and CD45RO counts of patients after HAART, therefore promoting immune reconstitution. PMID- 24228536 TI - [Experimental observation of SIVmac239 Chinese rhesus monkey model at sub-acute phase of AIDS]. AB - OBJECTIVE: To observe T lymphocyte subsets and indicators of changes in viral load in sub-acute period in Chinese rhesus monkey model of AIDS SIVmac239. To explore Virology related index variation in sub-acute period of the Chinese rhesus monkey model of AIDS. METHOD: To replicate Chinese rhesus monkey model of AIDS, healthy Chinese rhesus monkey was inoculated with SIVmac239 viral strain. To observe changes in T lymphocyte subsets indexes and viral load after infection with the simian immunodeficiency virus (SIV) in sub-acute period on an animal model. The clinical symptoms of the animal model was recorded simultaneously. RESULT: During the 10 weeks after SIV acute infection, body weight and BMI index were relatively stable, the difference was not significant at all time points. Twelve monkeys were tested SIV positive by real-time PCR after three days of infection. On the 7th day after infection, 15 monkeys were tested SIV positive. Viral load increased rapidly, but reached a peak on the 10th-14th day after infection, then showed a level of volatility decline. T lymphocyte subsets showed significant changes, among them, CD3% and CD3 counts fluctuated upward trend and reached to the highest level in two weeks after infection; of CD4% and CD4 count changes were not synchronized, CD4% declined trend while the CD4 count was an increasing trend after the infection; of CD8% and CD8 counts fluctuate upward trend, and reached to a highest level in two weeks after infection ;the ratio of CD4/CD8 and the counts of CD4CD28 T cells decreased significantly in two weeks after infection; the former followed by a slow decline, the latter followed by a rapid rise. Three mouths after the infection 3 monkeys showed significant clinical symptoms. One of the rhesus monkeys had symptoms of diarrhea and two of them had reduced food intake. CONCLUSION: This experiments established standardization of Chinese Rhesus monkeys used in the research of AIDS and provide a detailed contents in the changes of sub-acute phase. PMID- 24228537 TI - [Four hundred and eighty five cases of HIV/AIDS patients based on expert interpretation of characteristics of syndromes]. AB - This study aims to explore HIV traditional Chinese medicine (TCM) syndrome distribution and TCM syndrome evolution. The 485 cases of HIV/AIDS patients from 10 major regions of the AIDS epidemic in HIV. In this study, the interpretation of experts to explore the TCM syndromes in different routes of infection, different stage of disease, with syndrome distribution under different interventions. The results showed that Yang deficiency of spleen and kidney and liver Qi stagnation is the most common type in the patients who with sexually transmitted infections. TCM syndrome type most commonly seen in patients infected by the blood collection is yang deficiency of spleen and kidney and spleen deficiency wet-sheng. Including Yang deficiency of spleen and kidney with the highest frequency in patients with AIDS, people who with sexually transmitted infections and patients that treated with simple HAART were prone to liver stagnation and spleen-deficiency syndrome. In short, such as Yang deficiency of spleen and kidney, liver Qi stagnation, deficiency of both Qi and Yin, deficiency weakness of spleen-Qi, syndrome of damt-heat ftagnation were the main AIDS syndrome types. PMID- 24228538 TI - [Research on rules of distribution and development of traditional Chinese medicine syndromes of 2,237 HIV/AIDS cases]. AB - HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang. PMID- 24228539 TI - [Study of traditional Chinese medicine syndrome features of AIDS-related chronic diarrhea]. AB - OBJECTIVE: To study the AIDS-related chronic diarrhea in traditional Chinese medicine (TCM) clinical manifestations and syndrome factors, explore the characteristics of syndrome. METHOD: A multicenter, prospective collection of 311 cases of AIDS patients with chronic diarrhea, study the characteristics of TCM syndrome by using the method of descriptive statistics and exploratory factor analysis. RESULT: The common clinical manifestation of TCM: fatigue (229 cases, 73.63%), bowel (229 cases, 68.81%), diarrhea (194 cases, 62.38%), thin fur (201 cases, 64.63%), pink tongue (166 cases, 53.38%), greasy fur, thready pulse (126 cases, 40.51%), sink vein (64 cases, 20.58%), slippery pulse. 17 common factors were extracted, common disease syndrome factor as the spleen, stomach, liver, gallbladder and colon syndrome factors of disease, Qi, Yang deficiency, Qi stagnation, dampness and heat evil. CONCLUSION: AIDS-related chronic diarrhea symptoms involving multiple organs, the disease belongs to deficiency and excess. PMID- 24228540 TI - [Study on quality of life of asymptomatic HIV infected persons with traditional Chinese medicine]. AB - OBJECTIVE: Study on quality of life of asymptomatic HIV infected persons with traditional Chinese medical, which can provide the clinical basis for improving the quality of life. METHOD: This study applied a randomized, double-blind, and placeb-parallel control designed method to select 1 200 persons in the asymptomatic period of HIV infection as the subjects. The subjects were randomly divided into the treatment group and the control group at the ratio of about 2:1. According to the results of monthly differential diagnosis of TCM, the test group and the control group were given homologue Chinese drugs preparations and model Chinese drugs. The total study period was 18 months. Using PRO scale and the world health organization AIDS determination of quality of life short scale form (WHOQOL-HIV-BREF) to investigate asymptomatic HIV infected persons, according to different times, we calculated the total score and each domain score of quality of life of the treatment group and control group, we did statistical analysis. RESULT: Form the PRO scale,we can see that the treatment group showed a trend of stability, compared with the control group with significant statistical difference (P < 0.05) after 6 months; from the WHOQOL-HIV scale analysis, we can see that compared with before treatment, the quality of life of the treatment group was increased, the difference was significant (P < 0.05), but the quality of life of the control quality of life was decreased, the differences was significant (P < 0.05). CONCLUSION: Dialectical therapy of Chinese medicine can significantly improve the patient's quality of life, which can provide the basis for the prevention and control policy formulation and implementation with asymptomatic HIV infected persons. PMID- 24228541 TI - [Establish proposal of diagnosis and treatment of traditional Chinese medicine in AIDS patients with recurrent oral ulcerations]. AB - The pathogenesis of acquired immune deficiency syndrome-associated recurrent oral ulcerations (AIDS-ROU) remained obscure and these was no specific treatment for it. Syndrome differentiation in traditional Chinese medicine (TCM) focus on integral regulation and has an advantage of the disease that etiology and pathogenesis remain obscure. A draft of Chinese medicine diagnosis and treatment standard procedure for AIDS-ROU was established by literature retrieval and peer review. Two questionnaires were carried out to investigate the confirmation and advice of in-group specialist to key points of the draft including diagnosis, treatment and nursing. Then the procedures were revised accordingly. The preliminary results showed the recovery rate of complete questionnaires in the 1st survey was 96%. Specialists confirmed more on outline, case history and physical examinations, syndrome differentiation of hyperactivity of fire due to Yin deficiency syndrome (HFYDS), treatment of heat accumulated in heart and spleen syndrome (HAHSS) and HFYDS, treatment of western medicine and nursing. They held different opinions on incidence, treatment of deficiency of spleen-QI and stomach-QI syndrome (DSSS) and criterion of therapeutical evaluation. Cronbach coefficient alpha (CCA) was 0.998 and split-half reliability R was 0.91. Recovery rate of complete questionnaires in 2nd survey was 100%. Specialists confirmed more on outline, etiology and pathogenesis, case history and physical examination, auxiliary examination, diagnostic criteria, syndrome differentiation and treatment of HAHSS and HFYDS. They held different opinions on syndrome differentiation and treatment of intermingled cold and heat syndrome and DSSS, nursing and the other therapies. CCA was 0.428 and split-half reliability R was 0.96. Coefficient of variations of the 2nd survey were less than those of the 1st survey, which mean coordination was improved. Each single item in two surveys contributed less difference in overall results according to weight coefficients. A new revision of the procedure was preliminarily established according to results of two surveys. Experts'activeness, concentration and coordination were good in two surveys. They had reached consensus in key points of the draft including diagnosis, treatment and nursing on the whole. PMID- 24228543 TI - [Data mining analysis of professor Li Fa-zhi AIDS itchy skin medical record]. AB - OBJECTIVE: Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of itchy skin, provide the corresponding drug reference basis for Chinese medicine treatment of AIDS, skin itching. METHOD: By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS patients with skin pruritus, etiology and pathogenesis analysis, skin itching AIDS syndrome differentiation of old Chinese medicine treatment and medication rule. RESULT: The use of multi dimensional query analysis, core drug skin itching AIDS treatment in this study as a windbreak, cicada slough, bupleurum, Qufeng solution table drug, licorice detoxification efficacy of drugs, Radix Scutellariae, Kochia scoparia, clearing away heat and promoting diuresis medicine; core prescription for Jingfang San streak virus. CONCLUSION: Professor Li Fa-zhi treatment of AIDS in the skin itching Qufeng solution table dehumidification antipruritic treatment. PMID- 24228542 TI - [Construction and analysis of questionnaires on AIDS cough in traditional Chinese medicine diagnosis and treatment procedures]. AB - OBJECTIVE: To norm the behavior of AIDS cough in traditional Chinese medicine diagnosis and treatment and improve the clinical level of cough treatment for HIV/AIDS, and build AIDS cough diagnosis and treatment procedures in traditional Chinese medicine. METHOD: Combined with clinical practice,to formulate questionnaire on AIDS cough in traditional Chinese medicine diagnosis and treatment by both English and Chinese literature research to expertise consultation and verify the results of the questionnaires on the statistics using the Delphi method. RESULT: Questionnaire contents consist of overview, pathogeny, diagnosis standard, dialectical medication (phlegm heat resistance pulmonary lung and kidney Yin deficiency lung spleen-deficiency), treating spleen-deficiency (lung), moxibustion treatment and aftercare care and diet and mental, average (2.93-3.00), full mark rate (93.10%-100%) ranks average (9.91-10.67) and (287.50 309.50) of which are the most high value, and the variation coefficient is 0.00, the Kendall coefficient (Kendalls W) is 0.049 which is statistical significance, the questionnaire reliability value of alpha was 0.788. CONCLUSION: Preliminary standarded concept, etiology and pathogenesis, diagnosis and syndrome differentiation treatment of AIDS cough, basically recognised by the experts in this field, and laid the foundation of traditional Chinese medicine diagnosis and treatment on develop the AIDS cough specifications. PMID- 24228544 TI - [Data mining analysis of professor Li Fa-zhi AIDS herpes zoster medical record]. AB - OBJECTIVE: Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of herpes zoster and postherpetic neuralgia, provide reference for the use of Chinese medicine treatment of AIDS, herpes zoster and postherpetic neuralgia. METHOD: By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS of herpes zoster and postherpetic neuralgia patients, patients are input structured clinical information collection system, into the analysis of the data, carries on the research analysis theory of traditional Chinese medicine compatibility system algorithm and complex network analysis the use of complex networks. RESULT: The use of multi-dimensional query analysis of AIDS drugs, the core of herpes zoster and postherpetic neuralgia treated in this study are Scutellariae Radix, Glucyrrhizae Radix, Carthame Flos, Plantaginis Semen, Trichosamthis Fructus, Angelicae Sinensis Radix, Gentianae Radix; core prescription for Longdan Xiegan decoction and Trichosanthes red liquorice decoction. CONCLUSION: Professor Li Fa-zhi treatment of AIDS, herpes zoster and postherpetic neuralgia by clearing heat and removing dampness and activating blood circulation to. PMID- 24228545 TI - [Discussion on AIDS etiology, pathogenesis and treatment of traditional Chinese medicine]. AB - In recent years, Chinese medicine have gotten certain experience and made progress on the treatment of AIDS. Focus on AIDS main pathogenic factors of epidemic toxin and key pathogenesis of "epidemic toxin invasion, vital-Qi deficiency", this paper discuss on Chinese medicine theory of AIDS etiology and pathogenesis, and put forward the theory of "preventive treatment of disease" and enhanced the importance of "strengthening body resistance and eliminating evil" in the treatment of AIDS. PMID- 24228546 TI - [Analysis on efficacy action points of HIV/AIDS treatment with traditional Chinese medicine and antiretroviral drugs]. AB - Current international anti-HIV drug efficacy evaluation criteria including CD4 cell count and viral load. Antiviral therapy has good effect in suppressing viral load, although there are many limitations. More and more researchers began to focus on Chinese medicine. A large number of clinical practice shows that Chinese herbal medicine is good at improving patient immune function, reducing symptoms and improving quality of life, but the efficacy of inhibiting viral load was not obvious, clinical manifestation, immunological and virological indicators index inconsistency how to explain? This article from the perspective of theory and literature review, pointing out the similarities and differences of efficacy action points of Chinese and Western medicine treatment of AIDS from three aspects, including immune function, viral load and symptoms to explore the relevance of them. This paper proposed that immune function improvement and viral load change is not a direct inverse relationship (ie, improve immunity, the virus must fall); immunity improve followed by symptom relief and improved quality of life is more common to be seen; long-term improvement of immune function may follow by stable virus or gradual decline; the analysis still need to be testified in large sample, prolonged clinical observation in the future. PMID- 24228547 TI - [Application of cultivating Yuan and clearing blockage method on HIV/AIDS]. AB - According to HIV/AIDS being infectious and have a very long period of incubation, leading to immune system weakened and infected easily, we summarized its pathmechanism including Yuan Qi deficiency (vigour deficiency)and constraint (Qi depression,blood stagnancy, phlegm coagulation, poison accumulation), consequently treatment principle were raised--cultivates the Yuan and clear blockage. From viscera and Qi, blood, Yin and Yang perspective, we elaborate corresponding clinical application method and train of thought, that cultivating the Yuan method means tonify Qi firstly which emphasizes on the spleen and the kidney; Clear blockage method contains relieving liver for smooth Qi, invigorating spleen to remove phlem, promoting blood circulation and detoxification. In addition, cultivating the Yuan and clear blockage should cooperate closely based on traditional Chinese medicine diffrentiation, tonify deficiency should not used individually and vice verse. PMID- 24228548 TI - [Chinese classic formulas for treatment of acquired immune deficiency syndrome]. AB - The study of Chinese classic formulas for treating acquired immune deficiency syndrome is getting increasing popularity within traditional Chinese medicine (TCM) and integrative medicine worldwide. Over the past decades, considerable progress has been made in treating acquired immune deficiency syndrome by Chinese classic formulas. And it was found that Chinese classic formulas play an important role in the treatment of acquired immune deficiency syndrome. The paper systematically reviewed the current evidence and clinical application of Chinese classic formulas for acquired immune deficiency syndrome. It is worth noting that the key issue in applying Chinese classic formulas lies in grasping the objective indications of formulas and the rule of formula syndrome of the disease. PMID- 24228549 TI - [Discussion on treatment of AIDS by explling evil]. AB - Fever is the mostly common symptom in HIV/AIDS and is often accompanied by aignificant morbidity and prolonged hospitalization. Traditional Chinese medicine has a long history and rich experience to treat febrile diseases. We consider AIDS belongs to the category of warm disease in TCM, and the evil of "ai du" is the source of the disease. Explling evil is an important rule in effective treatment methods of warm disease, and plays a major role in the treatment of fever in HIV/AIDS from beginning to end. PMID- 24228550 TI - [Ethical issues and countermeasures in AIDS prevention]. AB - With the rapid spread of AIDS, the ethical issues of its prevention is intensify more and more, it mainly reflected in the four areas such as discrimination of disease and moral panic, individual rights and public health, privacy and right to know, social responsibility and behavior guidance. To resolve these ethical conflicts and safeguard legitimate rights of AIDS patients, we must adhere to love and tolerance, favorable and fair, the principles of autonomy and coordination, thus promoting AIDS prevention, maintaining social ethics and justice, equal and harmonious reconstruction of the ethical relationship. PMID- 24228551 TI - [Research progress in immune reconstruction of AIDS induced by modern medical intervention]. AB - Immune reconstruction in the treatment of AIDS has became one of hot topics in the field of aids research over the world. In this paper, the interventions of immune reconstitution were sumarized, but because of the clinical efficacy of these interventions still need to be verified and better solutions of their side effects also need to be found, clinical application of these interventions are still in process. PMID- 24228552 TI - [Research of Chinese herbal compound on promoting HIV immune reconstitution]. AB - This article reviews the research reports of Chinese herbal compound on AIDS immune reconstitution for nearly 20 years, found that Chinese herbal compound has exact clinical efficacy for AIDS immune reconstitution. Therefore, we should give full play to the unique advantages of Chinese herbal compound in improving immunity, thus improving symptoms and improve quality of life, to achieve optimal clinical treatment of AIDS. PMID- 24228553 TI - [Research progress of Chinese medicine treatment of HAART-related toxic and side effect]. AB - Highly active antiretroviral therapy (HAART) have made great progress in rapid inhibition of HIV, reduce the morbidity and mortality, etc; while it exists many limits, such as viruses rebound after discontinuation of drug, side effects, drug resistant. With the emergence of these problems, researchers explored therapies by traditional Chinese medicine, so as to achieve target of lower antiviral drug side effect, raising antiviral treatment adherence. Through a large number of clinical tests, we achieved encouraging effects in treating HAART related side effects by Chinese medicine. PMID- 24228554 TI - [Research progress of Chinese medicine treatment of HAART-related hyperlipidemia]. AB - Highly active antiretroviral therapy (HAART) for the treatment of HIV infection had a revolutionary impact, with the universal application of the anti-retroviral drugs, HAART-related adverse reactions have attracted more and more attention. HAART-related hyperlipidemia is one of the common adverse reactions with more and more scholars study the pathogenesis and therapy of hyperlipidemia in recent years. This article elaborated the latest research of Chinese medicine treatment of HAART-related hyperlipidemia. PMID- 24228555 TI - [Applications of acupuncture in relieving AIDS-related symptoms]. AB - AIDS is a serious threat to human health and has become a global public health problem. Highly active antiretroviral therapy (HAART) can effectively reduce AIDS mortality rate, but has limitations in improving the patient's symptoms and improve quality of life. The literatures about the therapeutic effect of acupuncture and moxibustion on HIV/AIDS were reviewed. The symptoms of HIV/AIDS and the procedures of treatments were analyzed. The acupuncture intervention on HIV/AIDS was investigated. It showed that the acupuncture intervention may markedly improve the condition of HIV/AIDS. From a clinical point of view, we discussed the acupuncture treatment of AIDS-related symptoms, effectiveness and safety evaluation. It may contribute to build a comprehensive treatment system in which acupuncture is dominated for HIV/AIDS. PMID- 24228556 TI - [Research progress of AIDS-related cancer]. AB - Kaposi's sarcoma, non-hodgkin's lymphoma and invasive cervical was named AIDS related cancer. This article introduces the appeal tumor research progress of modern medicine, and raises that antivirus, immune reconstitution and antitumor are the key factors in the treatment of AIDS-related cancer. Traditional Chinese medicine may play a role in the following aspect: relieve antiviral drug adverse reaction, have some antiviral effect,adjust the immune function,enhance efficacy and decrease toxicity of radiotherapy. According to the patients' immune function and the treatment phase, etc. It will contribute to improve the patients'lives and prolong the survival period to establish reasonable and comprehensive treatment strategies and to combine holistic therapy with individual therapy. PMID- 24228557 TI - [Research development of HIV drug resistance]. AB - Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance. PMID- 24228558 TI - [Pharmacological of Polygoni cuspidati rhizoma]. AB - Through searching some domestic or abroad literatures of rhizoma polygoni cuspidati in recent years, the paper summarized its pharmacological effects, including antibacterial, antiviral, anti-inflammatory, analgesic, cardiovascular system protection, liver protection, anti tumor, improving immunity pharmacology and so on. These studies indicated Polygoni Cuspidati Rhizoma was a kind of drugs with exploiting and using value. [Key words] PMID- 24228559 TI - [Advances on Cordyceps militaris constituents and pharmacological effect]. AB - Cordyceps militaris is a parasitic fungus in a variety of lepidopteran pupae and larvae. It was reported that Cordyceps militaris has strong activity on the immuregulation, tumor, virus, infecction. This review will focus on the advances its constituents and pharmacological effect. PMID- 24228560 TI - [Strategy and practice on scene application of molecular identification in Chinese medicine materials]. AB - Accurate and fast identification of Chinese medicine materials has been more difficult work during production and trade. However the molecular identification at present was only used in the laboratory, and difficult to scene application in producing area, market and pharmacy that limited its usage greatly. There are two important technologic bottlenecks for scene application: DNA rapid extraction and fast detection of DNA markers. This study developed a module system for the scene application of molecular identification in Chinese medicine materials. PMID- 24228561 TI - [Gene cloning and bioinformatics analysis of SABATH methyltransferase in Lonicera japonica var. chinensis]. AB - OBJECTIVE: To clone SABATH methyltransferase (rLjSABATHMT) gene in Lonicera japonica var. chinensis, and compare the gene expression and intron sequence of SABATH methyltransferase orthologous in L. japonica with L. japonica var. chinensis. It provide a basis for gene regulate the formation of L. japonica floral scents. METHOD: The cDNA and genome sequences of LjSABATHMT from L. japonica var. chinensis were cloned according to the gene fragments in cDNA library. The LjSABATHMT protein was characterized by bioinformatics analysis. SABATH family phylogenetic tree were built by MEGA 5.0. The transcripted level of SABATHMT orthologous were analyzed in different organs and different flower periods of L. japonica and L. japonica var. chinensis using RT-PCR analysis. Intron sequences of SABATHMT orthologous were also analyzied. RESULT: The cDNA of LjSABATHMT was 1 251 bp, had a complete coding frame with 365 amino acids. The protein had the conservative SABATHMT domain, and phylogenetic tree showed that it may be a salicylic acid/benzoic acid methyltransferase. Higher expression of SABATH methyltransferase orthologous was found in flower. The intron sequence of L. japonica and L. japonica var. chinensis had rich polymorphism, and two SNP are unique genotype of L. japonica var. chinensis. The motif elements in two orthologous genes were significant differences. CONCLUSION: The intron difference of SABATH methyltransferase orthologous could be inducing to difference of gene expression between L. japonica and L. japonica var. chinensis. These results will provide important base on regulating active compounds of L. japonica. PMID- 24228562 TI - [Study on molecular identification of water extracts from Gelsemium elegans and Lonicera japonica and its close species by specific PCR amplification]. AB - OBJECTIVE: To explore the new method of discriminating Gelsemium elegans from Lonicera japonica and its close species by using specific PCR amplification. METHOD: Thirteen samples of the different G. elegans materials and 58 samples of L. japonica, L. macranthoides and L. dasystyla were collected. The total DNA of the samples were extracted, and the DNA of G. elegans, L. japonica and L. macranthoides water extracts were extracted. PsbA-rnnH sequence from G. elegans was amplified by PCR and sequenced unidirectionally, ClustulW was used to align psbA-trnH sequences of the G. elegans and L. japonica and its close species from GenBank database. RESULT: All samples were amplified by PCR with specific primer, DNA from G. elegans would be amplified 97 bp whereas PCR products from all of Lonicera samples had not bands. CONCLUSION: Specific PCR amplification can be used to identify G. elegans from L. japonica and its close species successfully and is an efficient molecular marker for authentication of G. elegans and L. japonica and its close species. PMID- 24228563 TI - [Authenticate of Atractylodes macrocephala seed by amplification refractory mutation system]. AB - OBJECTIVE: To design specific primers and authenticate Atractylodes macrocephala from Atractylodes lancea and A. chinensis. METHOD: SNPs in the psbA-trnH sequences of Atractylodes were found by ClustulW program and Bioedit software. Primers for authentic A. macrocephala is designed according to the SNP site, and ITS sequence universal primers plus to the authentic primer to construct a multi PCR reaction system, and then optimized the PCR reaction system. RESULT: 172 bp band special for A. macrocephala were found using multi-PCR reaction. CONCLUSION: The multi-PCR reaction system could be applied to identify A. macrocephala seed. PMID- 24228564 TI - [Effect of PCR enhancer in molecular authenticate of Chinese herbal medicine]. AB - To evaluate the effect of PCR enhancer on molecular identification of Chinese herbal medicine, and select the optimal enhancers suitable for traditional Chinese medicine (TCM), genomic DNA from 180 kinds of Chinese herbal medicine was extract by CTAB method and alkaline lysis method, respectively. PCR success rate of five universal fragments (ITS2, psbA-trnH, rbcL, matK, trnL-trnF) was compared in a PCR system with and without enhancer. PCR efficiency of Real-time PCR was also compared in a PCR system with and without enhancer. Results showed that PCR success rate of ITS2,psbA-trnH, rbcL fragment was increased by using PVP and BSA. The PCR efficiency was decreased by PCR enhancer in Real-time PCR system. The results indicate that BSA and PVP as PCR enhancer can dramatically increase PCR success rate and genotyping accuracy in TCM molecular authentication. PMID- 24228565 TI - [Study on sequence characterized amplified region (SCAR) markers of Polygonum capitatum]. AB - OBJECTIVE: To establish sequence characterized amplified region markers of Polygonum capitatum. METHOD: The random primer was screened through RAPD to obtain the specific RAPD marker band, and the band was separated, extracted, cloned and sequenced. The specific primers were designed for conventional PCR reaction on the basis of the specific band, and the SCAR marker was acquired. RESULT: Screening from 50 RAPD primer, only C29 primer had 2 specific bands could distinguish P. capitatum from P. nepalense, then 4 pairs of specific primers were designed based on the 2 sequences of RAPD marker bands, and only 1 pair primer (Z1-2) was successfully converted into SCAR marker after repeated tests. CONCLUSION: The Z1-2 primer, could be used as an effective SCAR mark to identify Z300 DNA for P. capitatum. The SCAR mark was established and can be used as a molecular marker to distinguish P. capitatum from P. nepalense PMID- 24228566 TI - [Study on identification of Astragali Radix and Hedysari Radix by PCR amplification of specific alleles]. AB - To explore the new method of discriminating Astragali Radix and Hedysari Radix by using PCR amplification of specific alleles, 30 samples of the different Astragali Radix materials and 28 samples of Hedysari Radix were collected. The total DNA of all samples were extracted, trnL-trnF sequence from Astragali Radix and Hedysari Radix was amplified by PCR and sequenced unidirectionally. These sequences were aligned by using Clustul W. Primer was designed and the PCR reaction systems including annealing temperature, dNTP, etc were optimized. All samples were amplified by PCR with specific primer, DNA from Astragali Radix would be amplified 136 bp, whereas PCR products from all of Hedysari Radix were 323 bp. This method can detect 10% of intentional Hedysari Radix DNA into Astragali Radix. PCR amplification of alleles can be used to identify Astragali Radix and Hedysari Radix successfully and is an efficient molecular marker for authentication of Astragali Radix and Hedysari Radix. PMID- 24228567 TI - [Development of a lateral flow dipstick immunoassay for rapid detection of ginsenoside Re]. AB - A sensitive antibody-based lateral flow dipstick was developed for ginsenoside Re (GRe) detection. The stick consisted of a sample pad, a conjugate pad, membrane and an absorbent pad. The membrane was coated with two capture reagents, GRe-BSA conjugate and goat anti-mouse antibodies, forming a test line and a control line, respectively. The conjugate pad was saturated with colloidal gold particles coated with affinity purified monoclonal anti-GRe antibody. The visual detection limit was 200 microg x L(-1) of GRe and the reaction time was 10 min. The Panax ginseng roots were identified after these samples (10 mg) were extracted with 5 mL tap water for 30 min at room temperature, and the extracts were tested by the dipsticks and ELISA kit. The true and false P. ginseng could be distinguished with dipsticks. The dipstick could be used to detect the quality of the P. ginseng samples when the extract was diluted 100-folds. The results were compared with those obtained using an indirect competitive enzyme-linked immunosorbent assay (icELISA). The dipstick assay proved to be a sensitive and rapid tool for quality control of P. ginseng. PMID- 24228568 TI - [Optimization of extraction process of prescription of compound Nanxing pain relieving cataplasm by combining orthogonal design and pharmacodynamic experiment]. AB - OBJECTIVE: To discuss the optimum extraction process of compound Nanxing pain relieving cataplasm through orthogonal design and pharmacodynamic experiment METHOD: The orthogonal experiment method was adopted to optimize the ethanol extraction process with Angelica dahurica, Ligusticum chuanxiong and other herbs. The anti-inflammatory and analgesic effects of extracts from volatile oil in such herbs as syzygium aromaticum with different extraction processes were compared by tail pain tenderness test and food-pad swelling in mice, in order to optimize the extraction process of extracts from volatile oil in such herbs as syzygium aromaticum. RESULT: The optimum extraction process of A. dahurica, L. chuanxiong and other herbs for compound Nanxing pain-relieving cataplasm were as follows: adding 8-fold amount of 70% alcohol, extracting for 2 times with 1.5 h each time. The 95% ethnol extracts of syzygium aromaticum and other herbs had more effect in the increasing the threshold of pain and the inhibition of toe swelling of mice than volatile oil obtained from steam distillation as well as volatile oil and water decoction obtained from steam distillation. CONCLUSION: The method is simple and reliable that it can provide technical reference for the development of modern preparations of compound Nanxing pain-relieving cataplasm. PMID- 24228569 TI - [Study on drug release performance of compound Nanxing pain pastes with different stromata]. AB - Solvent and emulsion pressure-sensitive patches for compound Nanxing pain paste were prepared respectively in this study. Franz diffusion cell method was adopted to determine in vitro release of eugenol in compound Nanxing pain paste of the two stromata, with microfiltration membranes in place of skins. The results of the experiment demonstrated that solvent pressure-sensitive patches were superior to emulsion pressure-sensitive patches in terms of the accumulated release percentage of eugenol, with both of their release processes in line with Higuchi model and non-Fick diffusion mechanism. In conclusion, emulsion pressure sensitive stroma was more beneficial to in vitro release of eugenol in compound Nanxing pain paste. PMID- 24228570 TI - [Effect of ethanol concentration in receiver fluid on in vitro transdermal test]. AB - The present paper was designed to investigate the effect of varying concentrations of ethanol in receiver solution on the in vitro transdermal permeation of drug across the rat skin. 5-fluorouracil (5-FU) was used as the model drug on account of its good hydrophility, the excised rat skins were treated with different concentration ethanol prepared with normal saline for 12 h, then replaced by normal saline and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug. Meanwhile, scanning electron microscopy (SEM) was employed to monitor the effect of the different concentration ethanol on the stratum corneum of the rat skin. The ethanol below the concentration of 15% didn't significantly affect the barrier profile of the rat skin, while significant difference of in steady-state transdermal rate and lag times were observed when the concentration of ethanol was 20% or above. The SEM studies indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of ethanol was above 20%. The results showed that the low concentration of the ethanol (below 15%) didn't obviously affect the excised skin, yet the barrier profile of rat skin would significantly disrupted with the concentration of ethanol above 20%. PMID- 24228571 TI - [Study on transdermal characteristics of compound Nanxing pain-relieving cataplasm and effects of gaultherolin in prescriptions]. AB - OBJECTIVE: To study transdermal absorption characteristics of eugenol in compound Nanxing pain-relieving cataplasm, and discuss the effect of gaultherolin on the transdermal absorption of the cataplasm. METHOD: The improved franz diffusing cell was adopted with hairless mice skins as transdermal carriers. The content of eugenol in receptor liquid, skins and cataplasm were analyzed by HPLC and compared with the cataplasm without gaultherolin. RESULT: The penetration rates of eugenol of cataplasms with and without gaultherolin were 13.18 and 9.58 microg x cm(-2) x h(-1), with the retention amount in skins of (185.02 +/- 19.23) and (160.23 +/- 16.54) microg x g(-1) and the retention amount in cataplasms was (1.96 +/- 0.12) and (1.71 +/- 0.15) mg, respectively. CONCLUSION: Eugenol in compound Nanxing pain-relieving cataplasm has good pereutaoeous permeation. Gaultherolin in the cataplasm prescription can promote the absorption of eugenol. PMID- 24228572 TI - [Study on in vitro penetration of imperatorin]. AB - The object of this paper was to study the in vitro percutaneous factors that affect permeability of imperatorin. Excised abdominal skin of SD rats was used as the permeation model. Modified Franz diffusion cell was used to evaluate receiving solution, skin treatment and drug concentration on the effect of permeation. HPLC was established to determine drug content in recetpor at specified time points. The result showed that 20% ethanol and 0.5% Tween-80 could significantly increase the steady-state infiltration rate (Jass) of imperatorin. Skin treated of 20% ethanol, 20% ethanol-1% Tween-80 before experiments got an increased transdermal rate, whereas, those only accepted the treatment of 1% Tween-80 showed a decreased transdermal rate. The steady-state infiltration rate of imperatorin had a relationship with drug concentration, with the concentration increase, a bigger steady-state infiltration rate was obtained. When the drug concentration reached a certain concentration, the value was no longer changed. From the above research it could be found that ethanol could change the structure of the skin stratum corneum, which resulted in the increase of steady-state infiltration rate. The effect of Tween-80 on the steady-state permeation rate had nothing to do with skin structure. The concentration of drug in the diffusing cell had an effect on the penetration of imperatorin, which was the combined action of different diffusion route. PMID- 24228573 TI - [Study on transdermal behavior of Zhitong cataplasm]. AB - The aim of the present research was to study the transdermal absorbability of ferulic acid and imperatorin in Zhitong cataplasm. Using methanol to extract the effective components, HPLC was established to determine drug content in Zhitong cataplasm. The excised abdominal skin of nude rats was used as the permeation model Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected. The contents of ferulic acid and imperatorin in Zhitong cataplasm were 455.10, 371.66 microg x g(-1), respectively. Taken 20% ethanol- PBS (pH 8) as receiving solution, ferulic acid and imperatorin could be detected maximize, with the steady-state infiltration rates of 1.29, 0.15 microg x h(-1) x cm(-2), respectively. After 24 h, their penetration quantities were 30.03, 3.31 microg x cm(-2), with the penetration rates of 41.45%, 5.60%, respectively. The residual quantities of ferulic acid and imperatorin in skin were 0.69, 2.60 microg x cm(-2), with the retention rates of 0.95%, 4.40%, respectively. The in vitro transdermal behavior of ferulic acid in Zhitong cataplasm was close to a zero-order process, with the stratum corneum playing a rate-limiting role; whereas the percutaneous behavior of imperatorin was closer to Higuchi model, where diffusion played an important role in drugs permeation. PMID- 24228574 TI - [Effect of microemulsion technology on release of compounds in Zhitong cataplasm and content variation]. AB - To study the varieties of adhesives in gels on the basis of previous studies, dosage of adhesives required for forming of gels by using the single factor design, as well as the drug loading capacity of gels with the adhesiveness and stickiness as the scoring indicators, in order to determine the forming method of analgesic micro-emulsion gel. Subsequently, the improved Franz diffusing cell method was adopted to study the release of water-soluble components and liposoluble components in analgesic gels, with imperatorin and ferulic acid as index components. The results showed that analgesic micro-emulsion gel could promote the release of imperatorin and ferulic acid. Finally, HPLC was used to detect that the loss amount of volatile components in analgesic micro-emulsion gel was 23.13% lower than that in the original analgesic gel. In the experiment, we finally prepared finished products of micro-emulsion gel, discovered that the micro-emulsion technology is helpful to improve the synchronous release of water soluble components and liposoluble components in prescriptions and can reduce the loss of volatile components. PMID- 24228575 TI - [In vitro transdermal behavior of effective constituents in Chonghe gel]. AB - Chonghe gel originated from the Chinese ancient prescription, can be used for the treatment of diabetic foot. This experiment was to study the transdermal absorbability of paeoniflorin and osthole in Chonghe gel . Franz diffusing cells method was adopted for the in vitro model of rat belly skins. Paeoniflorin and osthole in the receiving liquid, skins and gel were determined by HPLC. The receiving liquid were screened, and Chonghe gel and Chonghe ointment were compared by transdermal absorbability. Result showed that ethanol-normal saline (2: 8) solution was the appropriate receiving liquid. The penetration rates of paeoniflorin and osthole were 78.07, 7.08 microg x cm(-2) x h(-1). respectively. In 24 h, the accumulated penetration rates were (31.51 +/- 1.33)%, (12.38 +/- 1.28)%, respectively. The retention rates of paeoniflorin and osthole in skin were (0.92 +/- 0.45)%, (4.81 +/- 1.03) %, respectively. The retention of osthole in skins was a drug reservoir. Transdermal behavior of effective constituents in Chonghe gel was more efficient than that in ointment. In vitro, the transdermal behavior of paeoniflorin in Chonghe gel was close to a Weibull process, while the behavior of osthole was close to Higuchi process. PMID- 24228576 TI - [Preparation of Kushen-Dilong nanoemulsion gel and transdermal characterization in vitro]. AB - OBJECTIVE: To prepare Kushen-Dilong nanoemulsion and nanoemuls-ion gel, and investigate its content, physical and chemical properties. Their transdermal properties in vitro were studied as well. METHOD: IPM acted as oil phase, EL35 as surfactant, EtOH as cosurfactant, Pheretima aqueous solution was added dropwise to the oil phase to prepare Kushen-Dilong nanoemulsion at room temperature using magnetic stirring. HPLC was used to determine the content of matrine and oxymatrine in the nanoemulsion. Transmission electron microscopy and laser particle size analyzer was used to determine the shape and size of the nanoemulsion. NP700 was used as substrate to prepare Kushen-Dilong nanoemulsion gel. Franz diffusion cell was used for the nanoemulsion and gel transdermal characteristics in vitro. RESULT: The Kushen-Dilong nanoemulsion was O/W nanoemulsion, its uniform particle size was 20.6 nm with roundness appearance and stable content. The steady-state permeation rate of Kushen-Dilong nanoemulsion, nanoemulsion gel, saturated aqueous solution, hydro gel were 0.1484, 0.1183, 0.0306, 0.0321 mg x cm(-2) x h(-1), respectively. CONCLUSION: The 24 h cumulative infiltration and infiltration rate of Kushen-Dilong nanoemulsion and nanoemulsion gel were better than the saturated aqueous solution and hydro gel, which could provide a new dosage form for Kushen-Dilong transdermal drug delivery. PMID- 24228577 TI - [Physicochemical properties and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion]. AB - The research aimed at investigating the physicochemical properties, stability and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion. Prepare total alkaloids of S. flavescens nanoemulsion and detect the determination of matrine and oxymatrine in the nanoemulsion using HPLC method. Transmission electron microscopy and laser particle size analyzer were utilized to detect the shape and size of the nanoemulsion respectively. And also the stability of nanoemulsion was studied under the conditions of low temperature (4 degrees C), normal temperature (25 degrees C) and high temperature (60 degrees C). Franz diffusion cell was used to research the transdermal absorption of nanoemulsion in vitro. The results found that the nanoemulsion we prepared presented appearance of rounded, uniform; its average diameter was (15.55 +/- 2.24) nm, and particle size distribution value was 0. 161; the appearance, diameter and percentage determination of total alkaloids of S. flavescens had no variations after 15 d under 4, 25, 60 degrees C respectively. The steady-state permeation rate was 4.564 1 microg x cm(-2) x h(-1), 24 h cumulative amount of penetration was 110.7 microg x cm(-2), which was 1.86 fold of 24 h cumulative amount of aqueous solution (59.41 microg x cm(-2)). All the results demonstrated total alkaloids of S. flavescens nanoemulsion had good permeability, and could provide a new preparation for its clinical application. PMID- 24228578 TI - [Research advance in medicinal plants from genus Coreopsis]. AB - There are about 100 species in the genus Coreopsis which distributed in the America, south of Africa and Hawaiian Islands, and 7 species are distributed in China. The inflorescences of Coreopsis tinctoria Nutt. is the Uigur herb 'Snow chrysanthemum' which is named 'Shemuju' with the effects of heat-cleaning, detoxicating, dampness-dissipating and dysentery-curing in the Xinhua Herbal Scheme. The chemical constituents from Coreopsis plants mainly contain flavonoids, phenylpropanoids, sesquiterpenes, and sterols, which show anti inflammatory activities in modern pharmaceutical research. This article presents an overview of the chemical constituents and pharmaceutical activities, prospects of development and exploitation of Coreopsis plants, hopefully to provide a basis for further research and development of Coreopsis plants. PMID- 24228579 TI - [Effect of baicalin on pattern recognition receptor TLR2/4-NOD2 and its significance of druggability]. AB - Activation pattern recognition receptors can cause the startup of downstream signaling pathways, the expression of inflammatory factors, and finally immunological inflammatory reaction. Either exogenous pathogenic microorganisms or endogenous tissue components can activate these pattern recognition receptors as ligands at varying degrees, and then cause the immunological inflammatory reaction. Therefore, it is of great significance to inhibit relevant receptors, as well as the immunological inflammatory reaction, in order to avoid tissue injury during the course of disease. Baicalin is able to specifically inhibit the expression of TLR2/4-NOD2, inhibit the expression of inflammatory factors IL 1beta, IL-6 and TNF-alpha, and thereby reducing the injury of the tissue cells during the course of disease. This effect is non-specific with tissues, which is of great theoretical and practical significance in druggability. In addition, the drug metabolism and toxicity of baicalin are also discussed for its druggability in this article. PMID- 24228580 TI - [Advance in studies on antioxidant activity of propolis and its molecular mechanism]. AB - Propolis is an adhesive substance mixed with plant resins collected by honeybees (Apis mellifera) and secretions from their mandibular gland and wax gland, with wide pharmacological activity and healthcare functions. Its antioxidant activity has long been regarded as one of the most important biological activities of propolis. This article summarizes studies on the antioxidant activity of propolis extracts from different geographic origins and with different extraction methods, as well as several important monomer active ingredients in propolis, and concludes the potential molecular mechanism of antioxidant activity of propolis and its monomer ingredients, with the aim of providing ideas for further studies on pharmacological activity of propolis, as well as reference for in-depth development of propolis products. PMID- 24228581 TI - [Key content and formulation of national Chinese materia medica resources survey at county level]. AB - According to National Census for Water, National Population Census, National Land and Resources Survey, and work experience of experimental measures for national Chinese materia medica resources(CMMR) survey,the national CMMR survey at the county level is the key point of whole survey, that includes organization and management, field survey, sorting data three key links. Organization and management works of national CMMR survey needs to finish four key contents, there are definite goals and tasks, practicable crew, preparation directory, and security assurance. Field survey works of the national CMMR survey needs to finish five key contents, there are preparation works for field survey, the choice of the key survey area (samples), fill in the questionnaire, video data collection, specimen and other physical collection. Sorting data works of the national CMMR survey needs to finish tree key contents, there are data, specimen and census results. PMID- 24228582 TI - [Chemical constituents of Paederia pertomentosa]. AB - Five constituents were extracted from the aerial part of Paederia pertomentosa and isolated by column chromatography. Their structures were elucidated by physicochemical properties and spectroscopic data analysis. The isolated compounds were identified as 1,2-dimethoxy-3,4-dihydroxyanthraquinone named as paederone (1), paederoside (2), deacetyl asperulosidic acid methyl ester (3), paederosidic acid (4) and methylpaederosidate (5). Compound 1 is a new compound which exhibits a significant inhibitory effect on Escherichia coli and Staphylococcus aureus. Compounds 2-5 were isolated from this plant for the first time. PMID- 24228583 TI - [Chemical constituents of chloroform fraction from leaves of Chimonanthus salicifolius]. AB - To explore anti-tumor active components of Chimonanthus salicifolius, the phytochemistry of the chloroform fraction from leaves extract was investigated by repeated silica gel column chromatography. Twelve compounds were isolated and their structures were identified by physicochemical properties and spectroscopic data analysis as 9-epi-blumenol C(1), blumenol C(2), (+)-dehydrovomifoliol (3), (+)-vomifoliol (4), robinlin (5), (-)-loliolide (6), isofraxidin (7), scopoletin (8), 6,7-dimethoxycoumarin (9), 6, 7, 8-trimethoxycoumarin (10), beta-sitostenone (11), and beta-stigmasterol(12). Compounds 1-6 belonging to nor-sesquiterpenoids were isolated from the family Calycanthaceae for the first time. Compound 1 was a new natural product. Compounds 7, 11 and 12 were obtained from this plant for the first time. PMID- 24228584 TI - [Chemical constituents from stems of Cistanche deserticola cultured in Tarim desert]. AB - In order to clarify the chemical constituents of Cistanche deserticola cultured in Tarim desert, a systematically phytochemical investigation was carried out. The chemical constituents were isolated by column chromatography, over silica gel, Sephadex LH-20, MCI gel, ODS and semi-preparative HPLC, and their structures were determined on the basis of MS, NMR spectroscopic data analysis, physicochemical properties and/or comparison with literature data Seventeen compounds were isolated from the 85% ethanol extract of the stems of C. deserticola cultured in Tarim desert. Their structures were identified as salsaside B (1), syringin (2), demethyl syrinyin (3), coniferin (4), (2E,6E)-3,7 dimethyl-8-hydroxyoctadien-1-O-beta-D-glucoside (5), (+)-syringaresinol (6), 2S,3S, 4S-trihydroxypentanoic acid (7), panaxytriol (8), beta-sitosterol-3-O-beta D-xylopyranoside (9), androsin (10), 3-methyl-but-2-en-1-yl-beta-D glucopyranoside (11), benzyl-glucopyranoside (12), 4-hydroxybenzyl-beta-D glucoside (13), nicotinamide (14), p-hydroxybenzoic acid (15), 4-hydroxy benzeneethanol (16), and galactitol (17). Compounds 3, 6-13 were isolated from this genus for the first time, and compounds 1, 4 and 5 were obtained from this species for the first time. PMID- 24228585 TI - [Chemical constituents from fungus Armillaria mellea]. AB - Ten compounds were isolated from cultures of the fungus Armillaria mellea by silica gel and Sephadex LH-20 column chromatographies. Their structures were identified by spectroscopic data analysis and compared their spectroscopic data with those reported in the literature as 2-hydroxy-4-methoxy-6-methylbenzoic acid (1), orsellinic acid (2), melleolide (3), ergosterol (4), genistein (5), daidzein (6), daucosterol (7), genistin (8), uracil (9) and D-mannitol (10). Compounds 1 10 were isolated from cultures of A. mellea for the first time. Among them, 14, 6 and 10 had been obtained from mycelia or rhizomorphs of A. mellea. The structure of compound 3 was determined by detailed analysis of its 1D and 2D NMR data in the solvent of DMSO for the first time. PMID- 24228586 TI - [Identification of chemical component from Ixeris sonchifolia and its injection by HPLC-ESI-MS(n)]. AB - A rapid analytical method was developed for the identification of components in Ixeris sonchifolia and its injection by HPLC-ESI-MS(n). The characterization of various components was analyzed according to the retention time of reference standard and mass spectrometry information. A profile of I. sonchifolia and its injection constituents was described and a total of three nucleosides, sixteen phenolic acids, seven flavonoids and twelve sesquiterpene lactones were identified or tentatively characterised. Twelve compounds were accurately identified with reference standards. Eleven of them, guanosine, 1-caffeoylquinic acid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic anhydride, 3,4 dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3-p-coumaroylquinic acid, 3 feruloylquinic acid, 5-p-coumaroylquinic acid and 4-feruloylquinic acid were reported for the first time in I. sonchifolia and its preparations. The structures of five isomers were deduced by theirs mass information and the fragmentation pattern of known compounds. The developed method was useful for the quality control and evaluation of this herb and its preparations. The HPLC-ESI MS(n) could be a promising tool for the rapid analysis of components from herbal medicines. PMID- 24228587 TI - [Study on quality control of Houttuynia Cordata, a traditional Chinese medicine by fingerprint combined with quantitative analysis of multi-components by single marker]. AB - To establish a new method of quality evaluation of Traditional Chinese medicine by fingerprint and quantitative analysis of multi-components by single marker method (QAMS). The quality evaluation method was established and validated with Houttuyniae Herba. Chlorogcnic acid was selected as markers of ingredients to establish HPLC fingerprint and internal reference standard to determine the contents of other 6 components (new chlorogcnic acid, cryptochlorogenic acid, rutin, hyperin, isoquercitrin, quercitrin) according to the relative correction factor. At the same time, the seven components were determined by external standard method. The accuracy and feasibility of QAMS was evaluated by comparison of the results between external standard method and QAMS. All tested samples contained the 12 common peaks , 7 of which was verified ,and there was no significant differences between the quantitative results of 7 ingredients of multi-components by single marker method and external standard method in 20 batches. The method of fingerprint combined with QAMS has been verified in Houttuyniae Herba and it is to be a new quality evaluation pattern for Traditional Chinese medicine. PMID- 24228588 TI - [HPLC fingerprint of flavonoids in Sophora flavescens and determination of five components]. AB - A simple and reliable method of high-performance liquid chromatography with photodiode array detection (HPLC-DAD) was developed to evaluate the quality of a traditional Chinese medicine Sophora flavescens through establishing chromatographic fingerprint and simultaneous determination of five flavonoids, including trifolirhizin, maackiain, kushenol I, kurarinone and sophoraflavanone G. The optimal conditions of separation and detection were achieved on an ULTIMATE XB-C18 column (4.6 mm x 250 mm, 5 microm) with a gradient of acetonitrile and water, detected at 295 nm. In the chromatographic fingerprint, 13 peaks were selected as the characteristic peaks to assess the similarities of different samples collected from different origins in China according to similarity evaluation for chromatographic fingerprint of traditional chinese medicine (2004AB) and principal component analysis (PCA) were used in data analysis. There were significant differences in the fingerprint chromatograms between S. flavescens and S. tonkinensis. Principal component analysis showed that kurarinone and sophoraflavanone G were the most important component. In quantitative analysis, the five components showed good regression (R > 0.999) with linear ranges, and their recoveries were in the range of 96.3% - 102.3%. This study indicated that the combination of quantitative and chromatographic fingerprint analysis can be readily utilized as a quality control method for S. flavescens and its related traditional Chinese medicinal preparations. PMID- 24228589 TI - [Effect of oxymatrine on JAK2/STAT3 signaling in renal tissues of rats with septic shock]. AB - OBJECTIVE: To explore the effect of oxymatrine (OMT) on JAK2/STAT3 signaling in renal tissues of rats with septic shock. METHOD: The cecal ligation and puncture (CLP) was adopted to establish the rat septic shock model. Fifty-six male SD rats were randomly divided into 7 groups: the sham operation group, the model (CLP) group, CLP + OMT high, middle, low-dose (52, 26, 13 mg x kg(-1), vena caudalis bolus) groups and the positive control (CLP + dexamethasone, 10 mg x kg(-1)) group. The pathological changes in renal tissues were examined with lightmicroscope. BUN content was determined by urine enzymatic method. Expressions of tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL 1beta) mRNA in renal tissues were determined by RT-PCR. Expression of JAK2 and STAT3 in renal tissues determined by Western blot. Changes in tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) contents in renal tissue were determined by radioimmunoassay. RESULT: OMT of different doses could inhibit the JAK2 and STAT3 activation in renal tissues (P<0.05), and decrease the protein expression of JAK2, STAT3, TNF-alpha and IL-1beta mRNA (P<0.05). Besides, it could reduce TNF-alpha and IL-1beta contents in renal tissue homogenate (P<0.05), serum BUN content (P<0.05), and improve such lesions as tissue hyperemia, edema and inflammatory cell infiltration, with identical results in medium and high-dose OMT groups, and the positive control group. CONCLUSION: OMT can inhibit JAK2/STAT3 signaling activity to reduce the expression of proin flammatory factors (TNF-alpha, IL-1beta) and treat the renal injury in rats with septic shock. PMID- 24228590 TI - [Study on molecular target promoting human neural stem cells of ginsenoside Rg1 by gene chip]. AB - OBJECTIVE: To screen out main molecular target promoting human neural stem cells (NSCs) of ginsenoside Rg1 by using the gene chip technology. METHOD: First, MTT assay was adopted to screen out the optimal concentration of Rg1-promoted NSC proliferation (120 mg x L(-1)). Then, on the 7th day after the Rg1-promoted NSC proliferation, the expression of target genes was observed by the gene chip technology. The most important target gene and signal transduction pathways were screened out through the data calculations. RESULT: On the 7th day after the Rg1 promoted NSC proliferation, obtained 440 differential genes, 266 significantly upregulated genes and 174 significantly down-regulated genes. HES1 gene, CAMP (cyclic adenosine monophosphate)-PKA (protein kinase A) and PI3K (phosphatidylinositol 3 kinase)-AKT signal transduction pathways were closely related to the NSC proliferation. CONCLUSION: The differentially expressed genes screened out by gene chip may provide new clues for studies on molecular mechanism of ginsenoside Rg1-promoted NSCs proliferation. PMID- 24228591 TI - [Valuation on analgesic, expectorant and antitussive effects of compatible use of Aconiti radix cocta and Fritillaria cirrhosa or Fritillaria thunbergii]. AB - OBJECTIVE: To study the analgesic, expectorant and antitussive effects of the compatible use of Aconiti Radix Cocta and Fritillaria cirrhosa or F. thunbergii with different matching ratio or dose in mice. METHOD: The two-factor, seven level uniform design method was adopted to observe the analgesic, expectorant and antitussive effects of the oral administration with the two combined decoctions in rats, with frequency of body torsions induced by acetum, secretion of phenol red in tracheas and frequency of coughs as indexes. Significant matching proportions and doses were collected for verification. RESULT: The effect on the frequency of body torsions: The combined decoctions could effectively reduce the frequency of body torsions. According to a regression analysis, Aconiti Radix Cocta and F. cirrhosa had the synergistic effect, which was maximized with a ratio of 1: 1. The 1: 1 combined decoction played the least role in reducing the frequency of body torsions with a total dose of more than 5 g x kg(-1). The effect on the secretion of phenol red in tracheas. The combined decoctions could effectively increase the secretion of phenol red in tracheas. According to a regression analysis, Aconiti Radix Cocta and F. thunbergii had the antagonism, which was maximized at the ratio of 1: 1, and minimized with a total dose of less than 10 g x kg(-1) and a ratio of 5: 1 between F. thunbergii and Aconiti Radix Cocta. The effect on the frequency of coughs. The combined decoctions could effectively reduce the frequency of coughs. According to a regression analysis, Aconiti Radix Cocta and F. cirrhosa had the antagonism, which was maximized at the ratio of more than 1: 5 and less than 10: 1. There was no interaction between Aconiti Radix Cocta and F. thunbergii. F. thunbergii could reduce the frequency of coughs, whereas Aconiti Radix Cocta showed no effect. CONCLUSION: The compatible application of Aconiti Radix Cocta and F. cirrhosa could enhance the analgesic effect of Aconiti Radix Cocta and reduce the expectorant and antitussive effects of F. cirrhosa, which vary according to different matching ratio and dose. The compatible application of Aconiti Radix Cocta and F. thunbergii shows no effect on the antitussive effect of F. thunbergii. This study provides experimental basis for in-depth studies on the combined effect of Aconiti Radix Cocta and Fritillaria--two of eighteen incompatible pairs. PMID- 24228592 TI - [Study on honeysuckle active ingredients and comparative analysis on their interactive mechanisms with different proteins]. AB - OBJECTIVE: To analyze and compare molecular mechanisms of active ingredients of honeysuckle (chlorogenic acid, CGA) with bovine lactoferrin (BLF) or bovine serum albumin (BSA). METHOD: The spectral experiment and the computer analog technology were combined to determine the binding parameters, energy transfer parameters and thermodynamic functions between CGA and proteins, study the molecular mechanism, and compare the differences in interactive mechanism between CGA and BLF or BSA. RESULT: The interactive mechanism between CGA and BLF or BSA was a dynamic molecular mechanism, whereas the static quenching mechanism existed between the interaction of CGA and BSA, with differences in the bonding intensity due to difference temperature. The binding distance r between CGA and BLF/BSA was very short, indicating the phenomenon of energy transfer. The results of the molecular modeling showed that the main interaction force between CGA and BLF or BSA was hydrogen bonds, together with Van der Waals' forces and hydrophobic effect. CONCLUSION: The computer analog shows consistent results with spectral experiment. PMID- 24228593 TI - [Action mechanism of drugs for preventing and treating coronary heart disease based on biological networks]. AB - Coronary heart disease (CHD) related genes and targets, as well as drug targets for preventing and treating CHD were taken as the study objects to build a CHD disease network and a drug action network preventing and treating CHD. Such topological characteristic parameters of the networks as degree distribution, characteristic path length, connectivity and heterogeneity were analyzed to verify the reliability of the networks. On that basis, the intersection calculation was conducted for both networks to analyze the drug action mechanism of their sub-networks. The disease network are composed of 15,221 nodes and 31,177 sides, while the drug action network preventing and treating CHD has 15,073 nodes and 32,376 sides. Both of their topological characteristic parameters showed scale-free small world structural characteristics. Two reaction pathways in the sub-networks-calcitonin gene-related peptide and IL-6 activated JAK/STAT were taken as examples to discuss the indirect action mechanism for preventing and treating CHD. The results showed that the biological network analysis method combining the disease network and the drug action network is helpful to further studies on the action mechanism of the drugs, and significant to the prevention and treatment of diseases. PMID- 24228594 TI - [Study on bioequivalence of new Wubei fast-release tablet]. AB - OBJECTIVE: To prepare a new Wubei fast-release tablet and study the pharmacokinetics and bioequivalence of self-prepared Wubei fast-release tablet and Wubei powder in Beagle dogs. METHOD: Wubei fast-release tablet was prepared with direct powder compression. Six Beagle dogs were randomly devided into two groups. They were orally administered with Wubei fast-release tablet and Wubei powder, respectively. Peimine concentrations in human plasma were determined by HPLC-MS/MS after administration. The pharmacokinetic parameters were calculated by DAS 2.0 using a non-compartmental analysis. The bioequivalence of fast-release tablet and powder was evaluated. RESULT: The main pharmacokinetic parameters of peimine in Wubei fast-release tablet as follows: Cmax (7.4 +/- 2.3) microg x L( 1), AUC(0-t) (59.13 +/- 15.25) microg x L(-1) x h(-1), Tmax (1.5 +/- 0.0) h. The main pharmacokinetic parameters of peimine in Wubei powder as follows: Cmax (8.0 +/- 1.7) microg x L(-1), AUC(0-t) (68.78 +/- 16.27) microg x L(-1) x h(-1), Tmax (1.5 +/- 0.0) h. The 90% confidence interval of InAUC(0-t), and lnCmax of peimine in Wubei fast-release tablet were 95.4% - 104.6%, 90.9% - 109.1% of corresponding parameters of Wubei powder, respectively. CONCLUSION: The self-prepared Wubei fast-release tablet and Wubei powder were bioequivalent. And the self-prepared Wubei fast-release tablet had simple production process, easy administration. PMID- 24228595 TI - Deciphering the role of natural variation in age-related protein homeostasis. AB - Understanding the genetic basis of age-related diseases is a critical step toward developing therapies that promote healthy aging. Numerous genes have been identified that modulate lifespan, but the influence of natural variation in aging has not been well studied. A new report utilizing a transgenic protein aggregation model in Caenorhabditis elegans has provided important tools and insights into the relationship between natural genetic variation, protein aggregation, and age-related pathology.See research article: http://www.biomedcentral.com/1741-7007/11/100. PMID- 24228596 TI - Arbuscular mycorrhizal symbiosis for sustainable cultivation of Chinese medicinal plants: a promising research direction. AB - Arbuscular mycorrhizal (AM) are symbiotic systems in nature and have great significance in promoting the growth and stress resistance of medicinal plants. During our literature search from the Chinese Scientific Information Database (Chinese National Knowledge Infrastructure, CNKI) we obtained 65 articles with "AM fungi" and "medicinal plant" as the key words, which indicates that in China, research efforts on these topics have been increasing. The main purposes of this review are to discuss the effects of mycorrhiza on the active ingredients of Chinese medicinal plants in comparison with results obtained in other plants in studies conducted by the international research community, and to introduce works published in Chinese journals to international colleagues. PMID- 24228597 TI - The principle of symmetry in acupuncture and its clinical applications. AB - The clinical practice of acupuncture and study of the traditional Chinese medicine literature has led to the observation that if the diaphragm is used as an axis of symmetry, there are many symmetrical points on the upper and lower halves of the body. The symmetrical points share several common properties, including physiological functions, mechanisms of pathogenesis and therapeutic effects. Employing these corresponding points on the upper and lower parts of the body simultaneously can frequently enhance the therapeutic outcome rather substantially. This phenomenon may be called the Principle of Symmetry. Traditional and modern scientific literature already provides evidence that verifies the reliability of this principle. Furthermore, this principle may be viewed as the derivative of the Thalamic Neuron Theory. PMID- 24228598 TI - Electroacupuncture at ST36 increases contraction of the gastric antrum and improves the SCF/c-kit pathway in diabetic rats. AB - Electroacupuncture (EA) at ST36 is effective for improving gastric motility. However, the underlying mechanism remains poorly understood. The aim of this study was to investigate the effects of EA on gastric contraction and to determine whether interstitial cells of Cajal (ICCs) are involved. Rats were randomized into control, diabetic (DM), diabetic with sham EA (DM + SEA), diabetic with low frequency EA (DM + LEA) and diabetic with high frequency EA (DM + HEA) groups. EA was performed everyday for four and eight weeks. Contractions in antrum strips were explored using the organ bath technique. Western blotting was employed to determine c-kit and transmembrane stem cell factor (M-SCF) expression in the gastric antrum, and levels of soluble stem cell factor (S-SCF) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The distribution of ICCs was further assessed by immunohistochemistry. The results were as follows: (1) Contractions in the DM group were attenuated at four and eight weeks, but LEA and HEA restored the attenuated contraction. (2) ICCs were significantly decreased at eight weeks without alteration at four weeks in DM group, but were rescued in the LEA and HEA groups. (3) Whereas M-SCF and S-SCF in the DM group were slightly decreased at four weeks and were dramatically reduced at eight weeks, LEA and HEA markedly enhanced SCF at eight weeks. Collectively, the data suggest that in diabetic rats, LEA and HEA at ST36 could facilitate contraction of the gastric antrum, possibly by involving the SCF/c-kit pathway. PMID- 24228599 TI - Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway. AB - This study was conducted to demonstrate myocardial protective effects and possible underlying mechanisms of vitexin on myocardial ischemia/reperfusion (I/R) injury in rats. Occluding the anterior descending artery for 30 min and restoring blood perfusion for 60 min in rat established a model of myocardial I/R. The elevation of the ST segment of Electrocardiograph (ECG) was observed. The infarct size of the rat heart was assessed by triphenyltetrazolium chloride staining (TTC). LDH, CK, SOD activities and MDA content were determined. An immunohistochemical analysis was applied to measure the expression of myocardial NF-kappaBp65 and TNF-alpha. ERK/phospho-ERKand c-Jun/phospho-c-Jun protein expression was examined via Western Blot. Vitexin significantly reduced the elevation of the ST segment of ECG and myocardial infarct size. LDH and CK activities and MDA content were attenuated in serum, while SOD activity was markedly enhanced. Vitexin significantly attenuated I/R-induced increases of myocardial NF-kappaB and TNF-alpha. Moreover, Western Blot analysis presented that vitexin markedly enhanced the expression of phospho-ERK and weakened the expression of phospho-c-Jun compared to I/R group. The significant protective effect against myocardial ischemical/reperfusion injury in rat, which is exhibited by vitexin, may be related to its antioxidative and anti-inflammatory effects by regulating inflammatory cytokines and the MAPK pathway. PMID- 24228600 TI - Inhibitory effects of BiRyuChe-bang on mast cell-mediated allergic reactions and inflammatory cytokines production. AB - BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-kappaB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-alpha, IL-6, and IL-8 as well as the activation of NF kappaB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF alpha and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8 Cineole, Linalool, Linalyl acetate, alpha-Pinene, and alpha-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells. PMID- 24228601 TI - Inhibitory effects of Brazilin on the vascular smooth muscle cell proliferation and migration induced by PDGF-BB. AB - Abnormal vascular smooth muscle cell (VSMC) proliferation and migration contribute to the pathogenesis of vascular diseases including atherosclerosis and restenosis. Brazilin isolated from the heartwood of Caesalpinia sappan L. has been reported to exhibit various biological activities, such as anti-platelet aggregation, anti-inflammation, vasorelaxation and pro-apoptosis. However, the functional effects of Brazilin on VSMCs remain unexplored. The present study investigated the potential effects of Brazilin on platelet-derived growth factor (PDGF)-BB induced VSMC proliferation and migration as well as the underlying mechanism of action. VSMC proliferation and migration were measured by Crystal Violet Staining, wound-healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase-9 (MMP-9) was carried out by gelatin zymography. Expression of adhesion molecules, cell cycle regulatory proteins, the phosphorylated levels of PDGF receptor beta (PDGF-Rbeta), Src, extracellular signal regulated kinase (ERK) and Akt were tested by immunoblotting. The present study demonstrated that pretreatment with Brazilin dose-dependently inhibited PDGF-BB stimulated VSMC proliferation and migration, which were associated with a cell-cycle arrest at G0/G1 phase, a reduction in the adhesion molecule expression and MMP-9 activation in VSMCs. Furthermore, the increase in PDGF-Rbeta, Src, ERK1/2 and Akt phosphorylation induced by PDGF-BB were suppressed by Brazilin. These findings indicate that Brazilin inhibits PDGF-BB induced VSMC proliferation and migration, and the inhibitory effects of Brazilin may be associated with the blockade of PDGF-Rbeta - ERK1/2 and Akt signaling pathways. In conclusion, the present study implicates that Brazilin may be useful as an anti-proliferative agent for the treatment of vascular diseases. PMID- 24228602 TI - Berberine reduces rat intestinal tight junction injury induced by ischemia reperfusion associated with the suppression of inducible nitric oxide synthesis. AB - Berberine (BBR) has been shown to attenuate the deleterious effects of ischemia/reperfusion (I/R) injury in the brain. We evaluated the effects of BBR on intestinal tight junction (TJ) changes during mesenteric I/R. I/R was induced in rats by the occlusion of the superior mesenteric artery and reperfusion. The rats were randomized into four groups: control, BBR, I/R, and I/R + BBR. Intestinal permeability was determined by the lactulose/mannitol test. The ileum and colon were harvested to assess mucosal injury and inducible nitric oxide synthase activity. The TJ ultrastructure was studied by transmission electron microscopy. The expressions and locations of the TJ proteins, occludin and ZO-1, in the epithelium were investigated by immunofluorescence microscopy. We also used Western blot analysis to detect the distribution of TJ proteins in lipid raft fractions. Our results suggest that I/R-induced intestinal TJ dysfunction can be improved by BBR, thereby demonstrating the therapeutic potential of BBR for intestinal I/R. PMID- 24228603 TI - Antithrombotic activities of epi-sesamin in vitro and in vivo. AB - Sesamin (SM) and epi-sesamin (ESM) were isolated from Asarum sieboldii and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell based thrombin and activated factor X (FXa). In addition, the effects of SM and ESM on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor alpha (TNF-alpha) activated human umbilical vein endothelial cells (HUVECs). Treatment with ESM, but not SM, resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and ESM inhibited production of thrombin and FXa in HUVECs; and ESM inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, ESM elicited anticoagulant effects in mice. In addition, treatment with ESM, but not SM, resulted in the inhibition of TNF-alpha induced production of PAI-1, and treatment with ESM resulted in a significant reduction of the PAI-1 to t-PA ratio. Of particular interest, inhibition of the anticoagulant activity by ESM was more potent than that by SM, likely due to differences between their three-dimensional structures. Collectively, ESM possesses antithrombotic activities and offers a basis for the development of a novel anticoagulant. PMID- 24228604 TI - EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion. AB - Extracts of Ginkgo biloba have been used in traditional medicines for centuries, and have potential for clinical applications in cerebral ischemia/reperfusion injury. However, standardized extracts have proven protective only as pre treatments, and the major mechanisms of action remain unclear. We explored the potential of the novel extract EGB1212, which meets the United States Pharmacopeia (USP) 31 standardization criteria for pharmaceutical use, as a post treatment after global cerebral ischemia/reperfusion (GCI/R) injury in a rat model. The pre-treated group was administered EGB1212 for 7 d prior to common carotid artery occlusion (i.e., ischemia, for 20 min). Post-treated rats received the same but starting 2 h after ischemia and continuing for 7 d. Seven days after GCI/R, brains of each group were processed for H&E staining of hippocampal CA1 neurons. Remaining rats underwent the Morris water maze and Y-maze tests of spatial learning and memory, beginning eight days after reperfusion. To assess hippocampal autophagy, light chain (LC)-3-I/LC3-II and Akt/pAkt were determined via a Western blot of rat hippocampi harvested 12, 24, or 72 h after reperfusion. EGB1212 pre- and post-treatments both improved neuronal survival and spatial learning and memory functions. Pre-treatment effectively reduced LC3-II levels and post-treatment resulted in significantly elevated pAkt levels. We conclude that EGB1212 exerted significant neuroprotection in GCI/R in both preventative and post-treatment settings. This extract shows great potential for clinical applications. PMID- 24228605 TI - Neuroprotective effects of Lycium chinense Miller against rotenone-induced neurotoxicity in PC12 cells. AB - Rotenone, an inhibitor of mitochondrial complex I, has been widely regarded as a neurotoxin because it induces a Parkinson's disease-like syndrome. The fruit and root bark of Lycium chinense Miller have been used as traditional medicines in Asia to treat neurodegenerative diseases. In this study, we examined the neuroprotective effects of Lycium chinense Miller extracts in rotenone-treated PC12 cells. Treatment with rotenone reduced PC12 cell viability and cellular ATP levels. Conversely, caspase 3/7 activity, the ratio of Bax:Bcl-2 expression levels, mitochondrial superoxide level, and intracellular calcium (Ca(2+)) concentration were elevated. Pretreatment with Lycium chinense Miller extracts significantly increased cell viability and ATP levels. Additionally, they attenuated caspase activation, mitochondrial membrane depolarization and mitochondrial superoxide production. Moreover, confocal microscopy showed that the mitochondrial staining pattern was restored from that of extracts treated cells and that the increase in intracellular Ca (2+) level was blunted by treatment with the extracts. Our results suggest that Lycium chinense Miller extracts may have the possible beneficial effects in Parkinson's disease by attenuating rotenone induced toxicity. PMID- 24228606 TI - Effects of tetramethylpyrazine on microglia activation in spinal cord compression injury of mice. AB - Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up regulation of TNF-alpha, IL-1beta and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury. PMID- 24228607 TI - Structure-activity relationship of 39 analogs of laetispicine with antidepressant properties. AB - The natural product Laetispicine ( N -isobutyl-(3,4-methylendioxyphenyl)-2E, 4E, 9E-undecatrienoamide), was isolated from the Piper laetispicum C. DC and screened, for its antidepressant activity and antinociceptive effects. Structure functional activities of five natural products indicated that biological activity is dependent on double bonds present within the benzene ring and a conjugated double bond located at positions 2-3 and 4-5 in the molecular structure. To further understand the structural-activity relationship of Laetispicine as a new potent and safe antidepressant, the structural-activity relationship of 39 analogs of Laetispicine were synthetized and tested in forced swimming tests in mice whilst also in protective effects against glutamate or H 2 O 2 induced apoptosis in PC12 cells. The results show that the compound 30 - N -isobutyl-11 (4-chlorophenyl) undeca-2E,4E,9E-trienamide exhibited the same activity as the parental compound Laetispicine, and furthermore, the effective dose of this compound is lower than Laetispicine. Therefore, the compound 30 might be a potentially useful therapy in the treatment of depression. For structure, the conjugated double bonds located at 2-3, 4-5 and isolated double bonds from benzene ring are necessary for the antidepressant activities no matter the different length of carbon chain; the isobutyl connected with acylamino also are necessary; and the benzodioxole moiety is replaceable, the halogen atom in phenyl ring at the para-position could enhance this kind of activity. PMID- 24228608 TI - Protective effect of Calculus Bovis Sativus on intrahepatic cholestasis in rats induced by alpha-naphthylisothiocyanate. AB - Calculus Bovis Sativus (also referred to as in vitro Cultured Calculus Bovis), an artificial substitute of natural Calculus Bovis (Niuhuang in Chinese, a traditional Chinese medicine), has been widely used to relieve fever, diminish inflammation and normalize gallbladder function in the last decade. This study aims to investigate the effects and possible mechanisms of Calculus Bovis Sativus on alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in rats. Calculus Bovis Sativus (50, 100 and 200 mg/kg per day) was intragastrically (i.g.) given to experimental rats for seven consecutive days. A single dose of ANIT (100 mg/kg i.g.) was given to rats on the fifth day to induce intrahepatic cholestasis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalinephosphatase (ALP) and total bilirubin (TBIL) were determined through biochemical methods. The bile duct was cannulated with a PE 10 polyethylene tube to collect bile for two hours and bile flow was calculated by the weight of each specimen. Moreover, the mechanism of Calculus Bovis Sativus was elucidated by determining liver malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. The biochemical observations were supplemented by histopathological examinations. Our results showed that Calculus Bovis Sativus (50, 100 and 200 mg/kg) significantly prevented ANIT-induced changes in bile flow and serum levels of ALT, AST, ALP and TBIL. Furthermore, Calculus Bovis Sativus (50, 100 and 200 mg/kg) significantly reduced the elevated hepatic MDA content induced by ANIT and increased the hepatic SOD activity suppressed by ANIT. Accordingly, histopathology of the liver tissue showed that pathological injuries were relieved after Calculus Bovis Sativus (50, 100 and 200 mg/kg) pretreatment. In conclusion, Calculus Bovis Sativus exerted a protective effect on ANIT-induced intrahepatic cholestasis in rats, which may result from the attenuated oxidative damage in liver tissues. PMID- 24228609 TI - Influence of six medicinal herbs on collagenase-induced osteoarthritis in rats. AB - Medicinal herbs have been effectively used for their anti-inflammatory activity, but their exact role has not yet been documented in scientific literature for the management of Osteoarthritis (OA). Since Sida cordifolia L., Piper longum L., Zingiber officinale Rosc., Ricinus communis L., Vitex negundo L. and Tribulus terrestris L. have been widely used in traditional medicine for their anti inflammatory activity, to evaluate anti-osteoarthritic activity of these herbs, we used a collagenase type II-induced osteoarthritis (CIOA) rat model. Arthritis was induced in wistar rats by intra-articular injection of collagenase type II. Powders of herbs were given orally for 20 days as a suspension in water (270 mg/kg b. wt.). The effects of the treatment in the rats were monitored by physiological parameters like body weight, knee diameter, paw retraction, paw volume, glycosaminoglycan (GAG) release, radiography and histopathology of knee joint. Selected herbs have significantly prevented body weight loss and knee swelling compared to arthritic control (CIOA). All test groups, including indomethacin (standard drug, 3 mg/kg), significantly reduced paw volume compared to CIOA. GAG release in the serum was significantly lowered in herb treated groups compared to indomethacin. The anterior posterior radiographs of S. cordifolia and P. longum treated groups showed a protective effect against OA. Histopathology revealed protection in the structure of the articular cartilage and in chondrocyte pathology as well as reduced clefting. Treatment with herbs has shown chondroid matrix within normal limits. From the results, we observed that S. cordifolia and P. longum possess potent anti-osteoarthritic activity. PMID- 24228610 TI - Interaction of rhubarb and methotrexate in rats: in vivo and ex vivo approaches. AB - Rhubarb, the rhizome of Rheum palmatum L. (RP), is a popular herb used in Chinese medicine prescriptions. RP contains a variety of polyphenolic anthraquinones, such as aloe-emodin, rhein, emodin and chrysophanol. Our previous study found that the anthraquinones in RP existed predominantly as glucuronides/sulfates in the bloodstream, which were putative substrates of MRPs. Methotrexate (MTX) is a widely used immunosuppressant and anticancer agent, but it has a narrow therapeutic index. The transcellular transport of MTX is mediated by multidrug resistance associated proteins (MRPs). This study investigated the effects of coadministration of RP on MTX pharmacokinetics in rats. The possible involvement of MRP 2 was verified by using cell models and various typical MRP 2 substrates. The results showed that coadministration of 0.5 mg/kg of RP significantly increased the AUC 0-t and MRT of MTX by 307% and 364%, and 1.0 g/kg of RP significantly increased the AUC 0-t and MRT of MTX by 602% and 419%, respectively. Cell line studies indicated that the activity of MRP 2 was inhibited by the metabolites of RP and rhein. In conclusion, concomitant administration of RP markedly increased the systemic exposure of MTX via inhibiting MRP 2-mediated excretion. PMID- 24228611 TI - Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells. AB - Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro. PMID- 24228612 TI - A novel paraboloid intracorporeal lithotripter: computer aided design analysis and in vitro comparison with holmium laser for large renal calculi. AB - PURPOSE: An intracorporeal lithotripsy probe tip was designed with a paraboloid shaped tip and compared with holmium laser for stone pulverization. MATERIALS AND METHODS: The paraboloid tip concept was developed and designed using computer aided design (CAD), fabricated, and patented. CAD analysis and in vitro comparison (with laser) of pulverization and propulsion dynamics were performed in an underwater hands-free bench arrangement using phantom stones. SPSS analysis for different energy cohorts was performed. RESULTS: CAD analysis: At "point contact" with the tip, the paraboloid lithotripter generated 3590 bars at generator settings of 4 bars. During "follow-up impacts," the tip pressure exponentially decreased (graduated tip pressure) and the lateral/centrifugal forces increased, converting the probe into a side-firing energy source. Bench analysis: At point contact, the paraboloid lithotripter at 2, 3, and 4 bars was comparable to that of a 6, 10, and 15 W laser, respectively (P<0.005). The paraboloid lithotripter showed a statistically significant advantage in breaking the phantoms, as against a laser that always bored through the phantom. Stone propulsion was comparable within all energy cohorts (P>0.05). CONCLUSION: The paraboloid lithotripter generates highly focused impact force with low propulsion, at point contact. As stone pulverization progresses, the tip forces exponentially decrease and the probe converts into a lateral firing energy source resulting in pulverization into larger fragments. Thus, the paraboloid lithotripter has all the advantages of laser at point contact and advantages of pneumatic lithotripter at follow-up hits, akin to being a bimodal energy source. PMID- 24228613 TI - Superbases in confined space: control of the basicity and reactivity of the proton transfer. AB - Endohedral functionalization of the molecular cavity of host molecules is in high demand in many areas of supramolecular chemistry. When highly reactive species are incarcerated in the confined space of a molecular cavity, deep changes of their chemical properties are expected. Here, we show that the superbasic properties of proazaphosphatranes can be improved in the confined space of the molecular cavity of hemicryptophane hosts. A general and modular procedure is described to prepare supramolecular superbases with various cavity sizes. The rate of proton transfer is strongly dependent on the shape and size of the inner cavity of the designed superbasic structure. Kinetic and thermodynamic data are strongly correlated to the space available around the basic center as revealed by the X-ray molecular structures analyses. PMID- 24228615 TI - Preterm birth, an unresolved issue. AB - Premature birth is the world's leading cause of neonatal mortality with worldwide estimates indicating 11.1% of all live births were preterm in 2010. Preterm birth rates are increasing in most countries with continual differences in survival rates amongst rich and poor countries. Preterm birth is currently an important unresolved global issue with research efforts focusing on uterine quiescence and activation, the 'omics' approaches and implementation science in order to reduce the incidence and increase survival rates of preterm babies. The journal Reproductive Health has published a supplement entitled Born Too Soon which addresses factors in the preconception and pregnancy period which may increase the risk of preterm birth and also outlines potential interventions which may reduce preterm birth rates and improve survival of preterm babies by as much as 84% annually. This is critical in order to achieve the Millennium Development Goal (MDG 4) for child survival by 2015 and beyond. PMID- 24228614 TI - Metabolic mechanisms of epigenetic regulation. AB - Chromatin modifications have been well-established to play a critical role in the regulation of genome function. Many of these modifications are introduced and removed by enzymes that utilize cofactors derived from primary metabolism. Recently, it has been shown that endogenous cofactors and metabolites can regulate the activity of chromatin-modifying enzymes, providing a direct link between the metabolic state of the cell and epigenetics. Here we review metabolic mechanisms of epigenetic regulation with an emphasis on their role in cancer. Focusing on three core mechanisms, we detail and draw parallels between metabolic and chemical strategies to modulate epigenetic signaling, and highlight opportunities for chemical biologists to help shape our knowledge of this emerging phenomenon. Continuing to integrate our understanding of metabolic and genomic regulatory mechanisms may help elucidate the role of nutrition in diseases such as cancer, while also providing a basis for new approaches to modulate epigenetic signaling for therapeutic benefit. PMID- 24228617 TI - Modes of activation of organometallic iridium complexes for catalytic water and C H oxidation. AB - Sodium periodate (NaIO4) is added to Cp*Ir(III) (Cp* = C5Me5(-)) or (cod)Ir(I) (cod = cyclooctadiene) complexes, which are water and C-H oxidation catalyst precursors, and the resulting aqueous reaction is investigated from milliseconds to seconds using desorption electrospray ionization, electrosonic spray ionization, and cryogenic ion vibrational predissociation spectroscopy. Extensive oxidation of the Cp* ligand is observed, likely beginning with electrophilic C-H hydroxylation of a Cp* methyl group followed by nonselective pathways of further oxidative degradation. Evidence is presented that the supporting chelate ligand in Cp*Ir(chelate) precursors influences the course of oxidation and is neither eliminated from the coordination sphere nor oxidatively transformed. Isomeric products of initial Cp* oxidation are identified and structurally characterized by vibrational spectroscopy in conjunction with density functional theory (DFT) modeling. Less extensive but more rapid oxidation of the cod ligand is also observed in the (cod)Ir(I) complexes. The observations are consistent with the proposed role of Cp* and cod as sacrificial placeholder ligands that are oxidatively removed from the precursor complexes under catalytic conditions. PMID- 24228616 TI - Chronic fluoxetine treatment reduces parvalbumin expression and perineuronal nets in gamma-aminobutyric acidergic interneurons of the frontal cortex in adult mice. AB - BACKGROUND: The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders, but cellular mechanisms underlying the antidepressant effect of FLX remain largely unknown. The generally accepted effect of chronic FLX treatment is increased adult neurogenesis in the hippocampal dentate gyrus. It was recently demonstrated that FLX treatments can reverse the established neuronal maturation of granule cells in the hippocampal dentate gyrus and of gamma-aminobutyric acidergic (GABAergic) interneurons in the basolateral amygdala. However, it is not clear whether this dematuration effect of FLX occurs in other brain regions. Thus, in this study, we used immunohistological analysis to assess the effect of FLX treatment on GABAergic interneurons in the medial frontal cortex (mFC) and reticular thalamic nucleus (RTN). RESULTS: Immunofluorescence analysis for perineuronal nets (PNNs), which is a marker of neuronal maturation, and for parvalbumin, calretinin, and somatostatin, which are markers for specific GABAergic interneuron type, showed lower number of parvalbumin-positive (+) cells and PNN+/parvalbumin+ cells in the mFC of FLX-treated mice compared to vehicle-treated mice. However, FLX treatment had no effect on the number of cells expressing calretinin and somatostatin in the mFC. In the RTN, the number of PNN+ cells and parvalbumin+ cells was unaltered by FLX treatments. Furthermore, the number of total GABA+ cells and apoptotic cells in the mFC was similar between vehicle- and FLX-treated mice, suggesting that FLX treatment did not induce cell death in this region. Rather, our findings suggest that the decreased number of parvalbumin+ cells in the mFC was due to a decreased expression of parvalbumin proteins in the interneurons. CONCLUSIONS: This study indicates that FLX decreases the levels of parvalbumin, a mature marker of fast-spiking interneurons, and PNNs in parvalbumin+ interneurons in the mFC, suggesting that FLX treatment induces a dematuration of this type of neurons. Induction of a juvenile-like state in fast-spiking inhibitory interneurons in these regions might be involved in the therapeutic mechanism of this antidepressant drug and/or some of its adverse effects. PMID- 24228618 TI - Engineered nanoparticles may induce genotoxicity. PMID- 24228620 TI - The serological response of working farm dogs to a vaccine containing Leptospira interrogans serovars Copenhageni and Pomona, and L. borgpetersenii serovar Hardjo. AB - AIMS: To evaluate the serological response in dogs to a commercial vaccine for use in cattle containing cultured strains of Leptospira interrogans serovars Copenhageni and Pomona, and L. borgpetersenii serovar Hardjo. METHODS: Blood samples were obtained from 67 working farm dogs on 12 farms, and the microscopic agglutination test (MAT) was used to measure titres to the Leptospira spp. serovars Pomona, Hardjo, and Copenhageni. Samples with a titre of <1:25 were defined as seronegative. Dogs that were seronegative to both Pomona and Hardjo (n=33) were randomised to either the vaccination (n=20) or control (n=13) groups. Seven of these dogs were seropositive to Copenhageni. Vaccinated dogs were given the three-component vaccine subcutaneously on two occasions, 4 weeks apart. MAT titres were measured again in both groups 2 weeks after the second vaccination. RESULTS: Of the vaccinated dogs, 20/20 (100%) developed titres to serovar Pomona, and 16/20 (80%) had titres >100; for serovar Hardjo, 19/20 (95%) dogs had titres, with 18/20 (90%) being >100; and for serovar Copenhageni, 15/17 (88%) dogs that were initially seronegative had titres, with 6/17 (35%) being >100. The median titres for Pomona and Hardjo (200 (95% CI=179-359) and 200 (95% CI=176-379), respectively) were lower than for Copenhageni (50 (95% CI=26-124)) in dogs originally seronegative (p<0.001). There was no association between titres to the different serovars. Of the 13 unvaccinated dogs, two developed titres to serovar Pomona, and three to Hardjo. All titres were <100. CONCLUSIONS: The tested vaccine was effective in raising antibodies to the three serovars, although the titres do not guarantee protection. CLINICAL RELEVANCE: There has been a recent increase in cases of leptospirosis attributed to the serovar Pomona in dogs in New Zealand, but the vaccines licensed for use in dogs in New Zealand for the prevention of leptospirosis only protect against Copenhageni/Icterohaemorrhagiae. The vaccine tested in this study produced titres to Pomona and Hardjo that suggest the vaccine could be useful for reducing disease caused by these serovars in working dogs in New Zealand. PMID- 24228619 TI - Site-specific orientation of an alpha-helical peptide ovispirin-1 from isotope labeled SFG spectroscopy. AB - Sum-frequency generation (SFG) vibrational spectroscopy is often used to probe the backbone structures and orientations of polypeptides at surfaces. Using the ovispirin-1 polypeptide at the solid/liquid interface of polystyrene, we demonstrate for the first time that SFG can probe the polarization response of a single-isotope-labeled residue. To interpret the spectral intensities, we simulated the spectra using an excitonic Hamiltonian approach. We show that the polarization dependence of either the label or the unlabeled amide I band alone does not provide sufficient structural constraints to obtain both the tilt and the twist of the ovispirin helix at a solid/liquid interface, but that both can be determined from the polarization dependence of the complete spectrum. For ovispirin, the detailed analysis of the polarized SFG experimental data shows that the helix axis is tilted at roughly 138 degrees from the surface normal, and the transition dipole of the isotope-labeled C?O group is tilted at 23 degrees from the surface normal, with the hydrophobic region facing the polystyrene surface. We further demonstrate that the Hamiltonian approach is able to address the coupling effect and the structural disorder. For comparison, we also collected the FTIR spectrum of ovispirin under similar conditions, which reveals the enhanced sensitivity of SFG for structural studies of single monolayer peptide surfaces. Our study provides insight into how structural and environmental effects appear in SFG spectra of the amide I band and establishes that SFG of isotope-labeled peptides will be a powerful technique for elucidating secondary structures with residue-by-residue resolution. PMID- 24228621 TI - Left ventricular post-infraction pseudoaneurysm mimicking mitral valve endocarditis. AB - In this report we present a patient who was initially diagnosed as suffering from mitral valve endocarditis. The proper use of diagnostic modalities revealed a pseudo aneurysm of the left ventricle which was mimicking mitral valve vegetations. This allowed better planning of the subsequent operation. The optimal preoperative diagnostic studies are discussed along with the proper surgical treatment. PMID- 24228623 TI - Effects of trans fats on prostacyclin production. AB - OBJECTIVES: Prostacyclin is a prostanoid derived from arachidonic acid that prevents thrombosis and is thereby expected to protect against heart disease, while trans fats present in partially hydrogenated oils interfere with arachidonic acid metabolism. Therefore, the objective of the present study was to investigate how fats with different proportions of linoleic acid and trans-18:1 affect prostacyclin released by cultured endothelial cells, and to compare these proportions with those found in commercially available foods. DESIGN: Soybean oil and hydrogenated soybean oil (coating fat) were mixed in different proportions to yield seven fat mixtures with proportions of linoleic acid ranging from 54.1% to 5.7% and trans-18:1 acid ranging from 0.4% to 43.9%. Human endothelial cells were cultured in each of the mixtures, and their phospholipid fractions were then separated and their fatty acids were analyzed by gas chromatography. The prostacyclin released by the cells was measured using RIA kits. Margarines and processed foods were purchased from the supermarket for comparison. RESULTS: Our work revealed that as the percentage of trans fat was increased, the amount of prostacyclin released dose-dependently and significantly (P < 0.0001) decreased, the concentration of linoleic and arachidonic acid decreased in the membrane phospholipids while the concentration of trans 18:1 acids increased, the prostacyclin decreased by 35-98%. Supermarket margarines had levels of trans fats similar to those that suppressed prostacyclin by 35-54%. Most processed foods labeled as trans-free contained trans fats. CONCLUSIONS: Trans fatty acids suppress prostacyclin production at levels found in commercial margarines, and processed foods labeled as trans-free could contribute to this effect if consumed in multiple servings or in addition to foods containing larger amounts of trans fats. PMID- 24228625 TI - Molecular methods for serovar determination of Salmonella. AB - Salmonella is a diverse foodborne pathogen, which has more than 2600 recognized serovars. Classification of Salmonella isolates into serovars is essential for surveillance and epidemiological investigations; however, determination of Salmonella serovars, by traditional serotyping, has some important limitations (e.g. labor intensive, time consuming). To overcome these limitations, multiple methods have been investigated to develop molecular serotyping schemes. Currently, molecular methods to predict Salmonella serovars include (i) molecular subtyping methods (e.g. PFGE, MLST), (ii) classification using serovar-specific genomic markers and (iii) direct methods, which identify genes encoding antigens or biosynthesis of antigens used for serotyping. Here, we reviewed reported methodologies for Salmonella molecular serotyping and determined the "serovar prediction accuracy", as the percentage of isolates for which the serovar was correctly classified by a given method. Serovar-prediction accuracy ranged from 0 to 100%, 51 to 100% and 33 to 100% for molecular subtyping, serovar-specific genomic markers and direct methods, respectively. Major limitations of available schemes are errors in predicting closely related serovars (e.g. Typhimurium and 4,5,12:i:-), and polyphyletic serovars (e.g. Newport, Saintpaul). The high diversity of Salmonella serovars represents a considerable challenge for molecular serotyping approaches. With the recent improvement in sequencing technologies, full genome sequencing could be developed into a promising molecular approach to serotype Salmonella. PMID- 24228626 TI - Then and Now: Examining How Consumer Communication and Attitudes of Direct-to Consumer Pharmaceutical Advertising Have Changed in the Last Decade. AB - This study examines changes over a 10-year period in consumer reports of communication with health care providers about direct-to-consumer advertised (DTCA) medications. Two rounds of survey data were collected in 2003 and 2012 using repeated cross-sectional procedures to examine consumer willingness to discuss DTCA medications, content and tone of those conversations, and attitudes about the advertisements. In total, 472 surveys were analyzed. Generally, we found physician-patient conversations, attitudes, and behaviors regarding DTCA have changed. Consumers in 2012 reported talking significantly less about the names of the advertised drug, comparing the advertised drug with their current medication, and sharing general information than consumers in 2003. Attitudes toward the advertisements were significantly more negative in 2012 compared to 2003. Of those who specifically asked for a prescription, the proportion of patients who received the prescription was significantly lower in 2012, despite research suggesting increased rates of prescriptions. These results are interpreted in light of previous research about the lack of research examining the actual communication between physicians and patients on this topic. Limitations of the study are provided along with directions for future research about DTCA and physician-patient communication. PMID- 24228622 TI - Venous endothelial injury in central nervous system diseases. AB - The role of the venous system in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and underinvestigated. Aside from cerebral venous infarcts, thromboembolic events, and cerebrovascular bleeding, several inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and optic neuritis, appear to be associated with venous vascular dysfunction, and the neuropathologic hallmark of these diseases is a perivenous, rather than arterial, lesion. Such findings raise fundamental questions about the nature of these diseases, such as the reasons why their pathognomonic lesions do not develop around the arteries and what exactly are the roles of cerebral venous inflammation in their pathogenesis. Apart from this inflammatory-based view, a new hypothesis with more focus on the hemodynamic features of the cerebral and extracerebral venous system suggests that MS pathophysiology might be associated with the venous system that drains the CNS. Such a hypothesis, if proven correct, opens new therapeutic windows in MS and other neuroinflammatory diseases. Here, we present a comprehensive review of the pathophysiology of MS, ADEM, pseudotumor cerebri, and optic neuritis, with an emphasis on the roles of venous vascular system programming and dysfunction in their pathogenesis. We consider the fundamental differences between arterial and venous endothelium, their dissimilar responses to inflammation, and the potential theoretical contributions of venous insufficiency in the pathogenesis of neurovascular diseases. PMID- 24228627 TI - Short and inflamed cervix predicts spontaneous preterm birth (COLIBRI study). AB - OBJECTIVE: To develop a new strategy of predicting spontaneous preterm birth (sPTB) by combination of transvaginal ultrasound (TVUS) assessment and inflammatory proteins detection in vaginal secretions. METHODS: Prospective study of 87 women referred for cervical length assessment with a standardized TVUS combined to vaginal secretions sampling. Samples were analyzed for presence of 10 cytokines. Main outcome was sPTB (<37 weeks of gestation). Associations were assessed with the chi-square, Fisher's exact test (p < 0.05) and Wald's logistic regression. RESULTS: sPTB occurred in 25.3% of women at a median gestational age of 35.6 weeks of gestation. Short cervix (<25 mm) (n = 24) was associated with sPTB (p < 0.01) as interleukine (IL)-1beta, IL-8 and IL-10 in vaginal secretions (p < 0.05). In multivariate analysis, short cervix and IL-8 in vaginal secretions were independently associated with sPTB (OR 3.58 (95%CI 1.02; 12.61) and 14.55 (95%CI 1.64; 128.83), respectively) as their combination (OR 4.33 (95%CI 1.25; 14.95)). By categorizing cervical length by presence of IL-8, sPTB occurred in 55.6% of women with a short inflamed cervix. CONCLUSION: COLIBRI study used a novel, single-step method of vaginal secretions sampling during TVUS and demonstrated that combination of short cervix and IL-8 in vaginal secretions is a promising sPTB predictive test. PMID- 24228628 TI - Correction to DNA translocation by human uracil DNA glycosylase: role of DNA phosphate charge. PMID- 24228629 TI - Experimental evidence and isotopomer analysis of mixotrophic glucose metabolism in the marine diatom Phaeodactylum tricornutum. AB - BACKGROUND: Heterotrophic fermentation using simple sugars such as glucose is an established and cost-effective method for synthesizing bioproducts from bacteria, yeast and algae. Organisms incapable of metabolizing glucose have limited applications as cell factories, often despite many other advantageous characteristics. Therefore, there is a clear need to investigate glucose metabolism in potential cell factories. One such organism, with a unique metabolic network and a propensity to synthesize highly reduced compounds as a large fraction of its biomass, is the marine diatom Phaeodactylum tricornutum (Pt). Although Pt has been engineered to metabolize glucose, conflicting lines of evidence leave it unresolved whether Pt can natively consume glucose. RESULTS: Isotope labeling experiments in which Pt was mixotrophically grown under light on 100% U-(13)C glucose and naturally abundant (~99% (12)C) dissolved inorganic carbon resulted in proteinogenic amino acids with an average 13C-enrichment of 88%, thus providing convincing evidence of glucose uptake and metabolism. The dissolved inorganic carbon was largely incorporated through anaplerotic rather than photosynthetic fixation. Furthermore, an isotope labeling experiment utilizing 1-(13)C glucose and subsequent metabolic pathway analysis indicated that (i) the alternative Entner-Doudoroff and Phosphoketolase glycolytic pathways are active during glucose metabolism, and (ii) during mixotrophic growth, serine and glycine are largely synthesized from glyoxylate through photorespiratory reactions rather than from 3-phosphoglycerate. We validated the latter result for mixotrophic growth on glycerol by performing a 2-(13)C glycerol isotope labeling experiment. Additionally, gene expression assays showed that known, native glucose transporters in Pt are largely insensitive to glucose or light, whereas the gene encoding cytosolic fructose bisphosphate aldolase 3, an important glycolytic enzyme, is overexpressed in light but insensitive to glucose. CONCLUSION: We have shown that Pt can use glucose as a primary carbon source when grown in light, but cannot use glucose to sustain growth in the dark. We further analyzed the metabolic mechanisms underlying the mixotrophic metabolism of glucose and found isotopic evidence for unusual pathways active in Pt. These insights expand the envelope of Pt cultivation methods using organic substrates. We anticipate that they will guide further engineering of Pt towards sustainable production of fuels, pharmaceuticals, and platform chemicals. PMID- 24228630 TI - Can reduce--the effects of chat-counseling and web-based self-help, web-based self-help alone and a waiting list control program on cannabis use in problematic cannabis users: a randomized controlled trial. AB - BACKGROUND: In European countries, including Switzerland, as well as in many states worldwide, cannabis is the most widely used psychoactive substance after alcohol and tobacco. Although approximately one in ten users develop serious problems of dependency, only a minority attends outpatient addiction counseling centers. The offer of a combined web-based self-help and chat counseling treatment could potentially also reach those users who hesitate to approach such treatment centers and help them to reduce their cannabis use. METHODS/DESIGN: This paper presents the protocol for a three-armed randomized controlled trial that will test the effectiveness of a web-based self-help intervention in combination with, or independent of, tailored chat counseling compared to a waiting list in reducing or enabling the abstention from cannabis use in problematic users. The primary outcome will be the weekly quantity of cannabis used. Secondary outcome measures will include the number of days per week on which cannabis is used, the severity of cannabis use disorder, the severity of cannabis dependence, cannabis withdrawal symptoms, cannabis craving, the use of alcohol, tobacco, and other non-cannabis illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of 8 modules designed to reduce cannabis use based on the principles of motivational interviewing, self-control practices, and methods of cognitive behavioral therapy. The two additional individual chat-counseling sessions in the additional chat condition will be based on the same therapy approaches and tailored to participants' self-help information data and personal problems. The predictive validity of participants' baseline characteristics on treatment retention and outcomes will be explored. DISCUSSION: To the best of our knowledge, this will be the first randomized controlled trial to test the effectiveness of online self help therapy in combination or without chat counseling in reducing or enabling the abstention from cannabis use. It will also investigate predictors of outcome and retention for these interventions. This trial is registered at Current Controlled Trials and is traceable as ISRCTN59948178. PMID- 24228631 TI - Q&A: Evolutionary capacitance. PMID- 24228632 TI - Correction: Early dysregulation of the memory CD8+ T cell repertoire leads to compromised immune responses to secondary viral infection in the aged. PMID- 24228633 TI - Successful management of trachea stenosis with massive substernal goiter via thacheobronchial stent. AB - A case of 65 year-old Chinese male patient with severe tracheal stenosis due to a massive substernal goiter, is presented. MRI and CT scan revealed that the massive substernal goiter was 9.3 * 6.1 * 4.7 cm in size, displacing the trachea and adjacent large vessels to the patient's right contributing to severe intrathoracic trachea compression up to 6 cm in length and the narrowest caliber of the trachea only 3.0 mm in diameter. To the best of our knowledge, optimal airway management for the massive substernal goiter resection was considered to be temporary tracheobronchial stent placement pre-operation. PMID- 24228635 TI - Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration. AB - High-throughput 'omics' technologies that generate molecular profiles for biospecimens have been extensively used in preclinical studies to reveal molecular subtypes and elucidate the biological mechanisms of disease, and in retrospective studies on clinical specimens to develop mathematical models to predict clinical endpoints. Nevertheless, the translation of these technologies into clinical tests that are useful for guiding management decisions for patients has been relatively slow. It can be difficult to determine when the body of evidence for an omics-based test is sufficiently comprehensive and reliable to support claims that it is ready for clinical use, or even that it is ready for definitive evaluation in a clinical trial in which it may be used to direct patient therapy. Reasons for this difficulty include the exploratory and retrospective nature of many of these studies, the complexity of these assays and their application to clinical specimens, and the many potential pitfalls inherent in the development of mathematical predictor models from the very high dimensional data generated by these omics technologies. Here we present a checklist of criteria to consider when evaluating the body of evidence supporting the clinical use of a predictor to guide patient therapy. Included are issues pertaining to specimen and assay requirements, the soundness of the process for developing predictor models, expectations regarding clinical study design and conduct, and attention to regulatory, ethical, and legal issues. The proposed checklist should serve as a useful guide to investigators preparing proposals for studies involving the use of omics-based tests. The US National Cancer Institute plans to refer to these guidelines for review of proposals for studies involving omics tests, and it is hoped that other sponsors will adopt the checklist as well. PMID- 24228636 TI - Whole genome resequencing in tomato reveals variation associated with introgression and breeding events. AB - BACKGROUND: One of the goals of genomics is to identify the genetic loci responsible for variation in phenotypic traits. The completion of the tomato genome sequence and recent advances in DNA sequencing technology allow for in depth characterization of genetic variation present in the tomato genome. Like many self-pollinated crops, cultivated tomato accessions show a low molecular but high phenotypic diversity. Here we describe the whole-genome resequencing of eight accessions (four cherry-type and four large fruited lines) chosen to represent a large range of intra-specific variability and the identification and annotation of novel polymorphisms. RESULTS: The eight genomes were sequenced using the GAII Illumina platform. Comparison of the sequences with the reference genome yielded more than 4 million single nucleotide polymorphisms (SNPs). This number varied from 80,000 to 1.5 million according to the accessions. Almost 128,000 InDels were detected. The distribution of SNPs and InDels across and within chromosomes was highly heterogeneous revealing introgressions from wild species and the mosaic structure of the genomes of the cherry tomato accessions. In-depth annotation of the polymorphisms identified more than 16,000 unique non synonymous SNPs. In addition 1,686 putative copy-number variations (CNVs) were identified. CONCLUSIONS: This study represents the first whole genome resequencing experiment in cultivated tomato. Substantial genetic differences exist between the sequenced tomato accessions and the reference sequence. The heterogeneous distribution of the polymorphisms may be related to introgressions that occurred during domestication or breeding. The annotated SNPs, InDels and CNVs identified in this resequencing study will serve as useful genetic tools, and as candidate polymorphisms in the search for phenotype-altering DNA variations. PMID- 24228637 TI - The relationship between the BRAF(V600E) mutation in papillary thyroid microcarcinoma and clinicopathologic factors. AB - BACKGROUND: The BRAF(V600E) mutation, which accounts for about 60-80% papillary thyroid carcinoma(PTC), has been identifiedas a prognostic marker for risk stratification of PTC patients. However, the BRAF(V600E) mutation as a prognostic marker in papillary thyroid microcarcinoma (PTMC) is unclear. METHODS: We performed a retrospective review of 101 patients who underwent surgery for PTMC. We studied the prevalence of the BRAF(V600E) mutation. The associations between the BRAF(V600E) mutation and clinicopathologic characteristics were analyzed. RESULTS: The BRAF(V600E) mutation was observed in 72 patients (71.3%). There was no statistically significant correlation in age, gender, multifocality, extrathyroidal extension, presence of Hashimoto thyroiditis, and lymph node metastasis between the BRAF(V600E) mutant group and wild group. CONCLUSIONS: The BRAF(V600E) mutation is not significantly associated with prognostic factors in PTMC. PMID- 24228638 TI - Factors influencing maternal nutrition in rural Nepal: an exploratory research project. AB - In this pilot project we examined factors contributing to maternal nutrition among women of child-bearing age in the Western Region of Nepal. We found that rural women are interested in learning about nutrition regardless of educational attainment and that level of education is strongly associated with interest in learning about nutrition (p <.001). Although the majority of women with no education expressed interest in learning about nutrition (71%), a substantial percentage (22%) were not interested. Education and the teaching of basic health messages may hold important benefits for improving maternal and child health. PMID- 24228639 TI - Radiopacity and hounsfield attenuation of cystine urolithiasis: case series and review of the literature. AB - OBJECTIVES: Given the high recurrence rate of cystine urolithiasis, understanding of the radiographic stone characteristics is important in following cystine stone formers over their lifetime. However, due to their infrequent incidence, in vivo radiographic properties of cystine stones have not been well characterized. The purpose of our study is to characterize the in vivo radiographic properties of cystine urolithiasis. METHODS: Patients with a cystine stone analysis and noncontrast computed tomography (NCCT) were extracted from our stone clinic database. Stone attenuation in Hounsfield units (HU) was measured for each stone and plain abdominal films (kidney, ureter, and bladder radiograph [KUB]) within 30 days of the NCCT prior to any intervention were reviewed by a blinded radiologist to assess whether urolithiasis could be visualized. RESULTS: Twenty patients met our study inclusion criteria. When plotted by attenuation, two distinct groups of stone attenuation were noted for cystine stone formers (p<0.001). The largest group (n=16) had an attenuation of <550 HU (424+/-106 HU), while a distinct second group (n=4) was >850 HU (972+/-134 HU). Sixteen patients had a KUB, with 88% of the stones being visualized by a blinded radiologist. Stone size and attenuation were not significantly different between visualized and nonvisualized stones via KUB, however, the body mass index was significantly higher in the nonvisualized group (34.4 vs 26.9 kg/m(2), p=0.03). CONCLUSIONS: Cystine stones were visualized by KUB, which has implications in post-treatment follow-up imaging. Though most cystine stones had an attenuation of <550 HU, a second distinct group of cystine stones were noted to have a high attenuation of >850 HU. HU measurements alone are not sufficient to differentiate cystine stones from other stone compositions. PMID- 24228640 TI - Message Quality and Standing to Support: A Qualitative Study of Support Messages Given to African-American HIV Survivors. AB - We interviewed 25 African American HIV survivors who were as much as 25 years distant from their original diagnoses. We asked them to tell us about both supportive and non-supportive messages they received upon learning of their HIV status. Their interviews showed evidence of the importance of what we call standing to support. This idea is that particular roles (e.g., medical or family) imply a duty to offer constructive support. Anyone without such a standing is essentially irrelevant to the provision of support. Successful performance of a standing requires ability (to give information, to be empathetic, etc.) but the performance must be activated by the person who needs support. We found contrasts in the quality of messages originating in each of the standings we studied: medical, family, friends, relational partners, churches, and community centers. Dual consideration of supportive and non-supportive messages is productive in understanding the different standings to support. PMID- 24228641 TI - Acute myocardial infarction complicated by shock: outcome analysis based on initial electrocardiogram. AB - OBJECTIVES: To assess the relation between initial ECG findings, presence of risk factors, coronary angiography findings, and clinical outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (CS). DESIGN: Data from a total of 5572 acute myocardial infarction patients admitted to the four tertiary hospitals during a period of 3 years were analyzed. CS on admission was present in 358 patients (6.4%). They were divided into four groups based on the admission ECG: ST-segment elevation (STEMI), ST-segment depression (STDMI), bundle branch block (BBBMI), and other ECG acute myocardial infarction. RESULTS: CS developed most frequently among BBBMI patients (in 12.1% of all BBBMIs, p < 0.001 vs. STEMI), followed by STEMI (6.7%), STDMI (4.4%), and other ECG acute myocardial infarction (2.3%). The risk of CS development was similar in patients with left bundle branch block (LBBB) (13.3%) and right bundle branch block (RBBB) (11.2%). The one-year mortality was highest among RBBBMI patients (66.7%, p < 0.001), followed by LBBBMI (48.6%), other ECG (47.1%), STEMI (41.7%), and STDMI patients (38.1%). CONCLUSIONS: RBBB on admission ECG is associated with the highest risk of CS development, frequent left main coronary artery affection, and unsuccessful revascularization. It is also an independent predictor of one-year mortality. PMID- 24228642 TI - Effect of vaccination coordinators on socioeconomic disparities in immunization among the 2006 Connecticut birth cohort. AB - OBJECTIVES: We examined socioeconomic status (SES) disparities and the influence of state Immunization Action Plan-funded vaccination coordinators located in low SES areas of Connecticut on childhood vaccination up-to-date (UTD) status at age 24 months. METHODS: We examined predictors of underimmunization among the 2006 birth cohort (n = 34,568) in the state's Immunization Information System, including individual demographic and SES data, census tract SES data, and residence in an area with a vaccination coordinator. We conducted multilevel logistic regression analyses. RESULTS: Overall, 81% of children were UTD. Differences by race/ethnicity and census tract SES were typically under 5%. Not being UTD at age 7 months was the strongest predictor of underimmunization at age 24 months. Among children who were not UTD at age 7 months, only Medicaid enrollment (adjusted odds ratio [AOR] = 0.6; 95% confidence interval [CI] = 0.5, 0.7) and residence in an area with a vaccination coordinator (AOR = 0.7; 95% CI = 0.6, 0.9) significantly decreased the odds of subsequent underimmunization. CONCLUSIONS: SES disparities associated with underimmunization at age 24 months were limited. Efforts focused on vaccinating infants born in low SES circumstances can minimize disparities. PMID- 24228643 TI - Estimating Wisconsin asthma prevalence using clinical electronic health records and public health data. AB - OBJECTIVES: We compared a statewide telephone health survey with electronic health record (EHR) data from a large Wisconsin health system to estimate asthma prevalence in Wisconsin. METHODS: We developed frequency tables and logistic regression models using Wisconsin Behavioral Risk Factor Surveillance System and University of Wisconsin primary care clinic data. We compared adjusted odds ratios (AORs) from each model. RESULTS: Between 2007 and 2009, the EHR database contained 376,000 patients (30,000 with asthma), and 23,000 (1850 with asthma) responded to the Behavioral Risk Factor Surveillance System telephone survey. AORs for asthma were similar in magnitude and direction for the majority of covariates, including gender, age, and race/ethnicity, between survey and EHR models. The EHR data had greater statistical power to detect associations than did survey data, especially in pediatric and ethnic populations, because of larger sample sizes. CONCLUSIONS: EHRs can be used to estimate asthma prevalence in Wisconsin adults and children. EHR data may improve public health chronic disease surveillance using high-quality data at the local level to better identify areas of disparity and risk factors and guide education and health care interventions. PMID- 24228644 TI - Racial/ethnic disparities in hypertension prevalence: reconsidering the role of chronic stress. AB - OBJECTIVES: We investigated the association between anticipatory stress, also known as racism-related vigilance, and hypertension prevalence in Black, Hispanic, and White adults. METHODS: We used data from the Chicago Community Adult Health Study, a population-representative sample of adults (n = 3105) surveyed in 2001 to 2003, to regress hypertension prevalence on the interaction between race/ethnicity and vigilance in logit models. RESULTS: Blacks reported the highest vigilance levels. For Blacks, each unit increase in vigilance (range = 0-12) was associated with a 4% increase in the odds of hypertension (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 1.00, 1.09). Hispanics showed a similar but nonsignificant association (OR = 1.05; 95% CI = 0.99, 1.12), and Whites showed no association (OR = 0.95; 95% CI = 0.87, 1.03). CONCLUSIONS: Vigilance may represent an important and unique source of chronic stress that contributes to the well-documented higher prevalence of hypertension among Blacks than Whites; it is a possible contributor to hypertension among Hispanics but not Whites. PMID- 24228645 TI - Impact of tobacco control on adult per capita cigarette consumption in the United States. AB - OBJECTIVES: We assessed the impact of tobacco control on adult per capita cigarette consumption in the United States from 1964 to 2011. METHODS: We used logit regression to model the diffusion of smoking from 1900 to 2011. We also projected hypothetical cigarette consumption after 1963 in the absence of tobacco control. Model predictors included historical events such as wars, specific tobacco control interventions, and other influences. RESULTS: Per capita consumption increased rapidly through 1963, consistent with S-shaped (sigmoid) diffusion. The course reversed beginning in 1964, the year of publication of the first surgeon general's report on smoking and health. Subsequent tobacco control policy interventions significantly reduced consumption. Had the tobacco control movement never occurred, per capita consumption would have been nearly 5 times higher than it actually was in 2011. CONCLUSIONS: Tobacco control has been one of the most successful public health endeavors of the past half century. Still, the remaining burden of smoking in the United States augurs hundreds of thousands of deaths annually for decades to come. Reinvigorating the tobacco control movement will require novel interventions as well as stronger application of existing evidence-based policies. PMID- 24228646 TI - MPH education for the 21st century: motivation, rationale, and key principles for the new Columbia public health curriculum. AB - Public health is at a watershed moment. The world's health needs are changing, and complex problems require interdisciplinary approaches and systems-based solutions. Our longer lives and changing environments necessitate life-course and structural approaches to prevention. This argues strongly for public health graduate education that adequately prepares trainees to tackle emerging challenges and to lead now and in the future. Nearly a century of scholarship and scientific advances may offer a blueprint for training the next generation of public health leaders. We articulate a case for change; discuss some of the foundational principles that should guide public health education; and discuss what such a change might look like building on prior scholarship, on the examples set by other disciplines, and on our own experience. PMID- 24228647 TI - Kumar et al. respond. PMID- 24228648 TI - Home renovation, family history of atopy, and respiratory symptoms and asthma among children living in China. AB - OBJECTIVES: To investigate the association of indoor air pollution with the respiratory health of children, we evaluated the associations of children's respiratory symptoms with asthma and recent home renovation. METHODS: We conducted a cross-sectional survey in a school recruitment sample of 31,049 children aged 2 to 14 years in 25 districts of 7 cities of northeast China in 2008-2009. The children's parents completed standardized questionnaires characterizing the children's histories of respiratory symptoms and illness, recent home renovation information, and other associated risk factors. RESULTS: The effects of home renovation in the past 2 years were significantly associated with cough, phlegm, current wheeze, doctor-diagnosed asthma, and current asthma. The associations we computed when combining the status of home renovation and family history of atopy were higher than were those predicted from the combination of the separate effects. However, the interactions between home renovation and family history of atopy on a multiplicative scale were not statistically significant (P>.05). CONCLUSIONS: Home renovation is associated with increases in the prevalence of respiratory symptoms and asthma in children. The effects of different renovation materials on child respiratory health should be studied further. PMID- 24228649 TI - Associations between macrolevel economic factors and weight distributions in low- and middle-income countries: a multilevel analysis of 200,000 adults in 40 countries. AB - OBJECTIVES: We examined associations between macrolevel economic factors hypothesized to drive changes in distributions of weight and body mass index (BMI) in a representative sample of 200,796 men and women from 40 low- and middle income countries. METHODS: We used meta-regressions to describe ecological associations between macrolevel factors and mean BMIs across countries. Multilevel regression was used to assess the relation between macrolevel economic characteristics and individual odds of underweight and overweight relative to normal weight. RESULTS: In multilevel analyses adjusting for individual-level characteristics, a 1-standard-deviation increase in trade liberalization was associated with 13% (95% confidence interval [CI] = 0.76, 0.99), 17% (95% CI = 0.71, 0.96), 13% (95% CI = 0.76, 1.00), and 14% (95% CI = 0.75, 0.99) lower odds of underweight relative to normal weight among rural men, rural women, urban men, and urban women, respectively. Economic development was consistently associated with higher odds of overweight relative to normal weight. Among rural men, a 1 standard-deviation increase in foreign direct investment was associated with 17% (95% CI = 1.02, 1.35) higher odds of overweight relative to normal weight. CONCLUSIONS: Macrolevel economic factors may be implicated in global shifts in epidemiological patterns of weight. PMID- 24228650 TI - Weight status and sexual orientation: differences by age and within racial and ethnic subgroups. AB - OBJECTIVES: We determined differences in weight at age 18 years and at current age and weight change by sexual orientation within different racial/ethnic populations, stratifying by gender. METHODS: We used 2001-2007 data from the California Health Interview Survey, resulting in an unweighted sample of 120,274 individuals aged 18 to 74 years. Using regression models, we examined overweight status and change in weight by sexual orientation, stratifying by race/ethnicity and gender. RESULTS: Compared with heterosexual women of the same race/ethnicity, White and African American lesbians and bisexuals had increased likelihood of being overweight at age 18 years and maintaining overweight status during adulthood. Sexual minority status was unrelated to weight among Latinas and inconsistently linked to weight among Asian women compared with heterosexual women of the same race/ethnicity. Sexual minority status was protective against unhealthy weight among White, African American, Asian, and Latino men compared with heterosexual counterparts of the same race/ethnicity. This protective effect was seen after age 18 years except among African American bisexual men. CONCLUSIONS: Our findings indicate a need for age- and culture-sensitive interventions that reduce weight or prevent weight gain in sexual minority women and men. PMID- 24228651 TI - Effect of race/ethnicity and socioeconomic status on pandemic H1N1-related outcomes in Massachusetts. AB - OBJECTIVES: We linked hospital discharge and American Community Survey and US Census data to investigate 2009 H1N1 influenza (H1N1)-related outcomes by racial/ethnic groups and socioeconomic status (SES). METHODS: We examined the population discharged from any acute care hospital in Massachusetts and calculated rates of intensive care unit (ICU) stay by racial/ethnic and SES groups between April 26 and September 30, 2009. We used logistic regression models to identify predictors of ICU stay. RESULTS: Of 4874 H1N1-related hospitalizations, 526 (11%) were admitted to the ICU. Those in less affluent SES groups had lower risk of ICU stay than the most affluent SES group. Compared with Whites, Hispanics had significantly lower risk of 2009 H1N1-related ICU stay (odds ratio = 0.52; 95% confidence interval = 0.32, 0.86). Only 13% of Whites admitted to the ICU were in the lowest SES group, compared with 63% of Hispanics and 43% of Blacks. CONCLUSIONS: To our knowledge, this is the first statewide description of 2009 H1N1 influenza-related ICU stays according to racial/ethnic group and SES in the United States. Future work should investigate evidence related to social determinants of health among racial/ethnic groups to reduce disparities in relation to pandemic influenza. PMID- 24228652 TI - Reaching children never previously vaccinated for influenza through a school located vaccination program. AB - OBJECTIVES: We determined the success of the school-located vaccination (SLV) program, implemented in 2009 in New York City to deliver pandemic influenza A (H1N1) monovalent vaccine (pH1N1), versus provider offices in reaching children who had never previously received influenza vaccine. METHODS: We compared the immunization history of children vaccinated in school versus provider offices. We included records in the Citywide Immunization Registry with pH1N1 administered between October 2009 and March 2010 to elementary school-aged children. RESULTS: In total, 96,524 children received pH1N1 vaccine in schools, and 102,933 children received pH1N1 vaccine in provider offices. Of children vaccinated in schools, 34% had never received seasonal influenza vaccination in the past, compared with only 10% of children vaccinated at provider offices (P < .001). Children vaccinated in schools were more likely to have received a second dose of pH1N1 in 2009-2010 than those vaccinated in provider offices (80% vs 45%). CONCLUSIONS: The SLV program was more successful at reaching children who had never received influenza immunization in the past and should be considered as a strategy for delivering influenza vaccine in routine and emergency situations. PMID- 24228653 TI - Six components necessary for effective public health program implementation. AB - Public health programs succeed and survive if organizations and coalitions address 6 key areas. (1) Innovation to develop the evidence base for action; (2) a technical package of a limited number of high-priority, evidence-based interventions that together will have a major impact; (3) effective performance management, especially through rigorous, real-time monitoring, evaluation, and program improvement; (4) partnerships and coalitions with public- and private sector organizations; (5) communication of accurate and timely information to the health care community, decision makers, and the public to effect behavior change and engage civil society; and (6) political commitment to obtain resources and support for effective action. Programs including smallpox eradication, tuberculosis control, tobacco control, polio eradication, and others have made progress by addressing these 6 areas. PMID- 24228654 TI - 50 years since the first Surgeon General's report on smoking and health: a happy anniversary? PMID- 24228655 TI - Network exposure and homicide victimization in an African American community. AB - OBJECTIVES: We estimated the association of an individual's exposure to homicide in a social network and the risk of individual homicide victimization across a high-crime African American community. METHODS: Combining 5 years of homicide and police records, we analyzed a network of 3718 high-risk individuals that was created by instances of co-offending. We used logistic regression to model the odds of being a gunshot homicide victim by individual characteristics, network position, and indirect exposure to homicide. RESULTS: Forty-one percent of all gun homicides occurred within a network component containing less than 4% of the neighborhood's population. Network-level indicators reduced the association between individual risk factors and homicide victimization and improved the overall prediction of individual victimization. Network exposure to homicide was strongly associated with victimization: the closer one is to a homicide victim, the greater the risk of victimization. Regression models show that exposure diminished with social distance: each social tie removed from a homicide victim decreased one's odds of being a homicide victim by 57%. CONCLUSIONS: Risk of homicide in urban areas is even more highly concentrated than previously thought. We found that most of the risk of gun violence was concentrated in networks of identifiable individuals. Understanding these networks may improve prediction of individual homicide victimization within disadvantaged communities. PMID- 24228656 TI - The impact of childhood mobility on exposure to neighborhood socioeconomic context over time. AB - We used the 1998-1999 Early Childhood Longitudinal Study-Kindergarten Cohort, with data collected in kindergarten, first, third, fifth, and eighth grades, in a descriptive analysis of associations between early childhood residential mobility frequency and neighborhood context changes. We found that children who move frequently appear initially to move into higher-socioeconomic-status neighborhoods but eventually move back to lower-socioeconomic-status neighborhoods, exposing frequent movers to diverse neighborhood contexts. These findings have implications for policy and research that seeks to link neighborhood context to health. PMID- 24228657 TI - An increasing socioeconomic gap in childhood overweight and obesity in China. AB - We used a new conceptual framework that integrates tenets from health economics, social epidemiology, and health behavior to analyze the impact of socioeconomic forces on the temporal changes in the socioeconomic status (SES) gap in childhood overweight and obesity in China. In data from the China Health and Nutrition Survey for 1991 to 2006, we found increased prevalence of childhood overweight and obesity across all SES groups, but a greater increase among higher-SES children, especially after 1997, when income inequality dramatically increased. Our findings suggest that for China, the increasing SES gap in purchasing power for obesogenic goods, associated with rising income inequality, played a prominent role in the country's increasing SES gap in childhood obesity and overweight. PMID- 24228658 TI - McGovern's Senate Select Committee on Nutrition and Human Needs versus the meat industry on the diet-heart question (1976-1977). AB - For decades, public health advocates have confronted industry over dietary policy, their debates focusing on how to address evidentiary uncertainty. In 1977, enough consensus existed among epidemiologists that the Senate Select Committee on Nutrition and Human Need used the diet-heart association to perform an extraordinary act: advocate dietary goals for a healthier diet. During its hearings, the meat industry tested that consensus. In one year, the committee produced two editions of its Dietary Goals for the United States, the second containing a conciliatory statement about coronary heart disease and meat consumption. Critics have characterized the revision as a surrender to special interests. But the senators faced issues for which they were professionally unprepared: conflicts within science over the interpretation of data and notions of proof. Ultimately, it was lack of scientific consensus on these factors, not simply political acquiescence, that allowed special interests to secure changes in the guidelines. PMID- 24228659 TI - Trends in the educational gradient of mortality among US adults aged 45 to 84 years: bringing regional context into the explanation. AB - OBJECTIVES: We investigated trends in the educational gradient of US adult mortality, which has increased at the national level since the mid-1980s, within US regions. METHODS: We used data from the 1986-2006 National Health Interview Survey Linked Mortality File on non-Hispanic White and Black adults aged 45 to 84 years (n = 498,517). We examined trends in the gradient within 4 US regions by race-gender subgroup by using age-standardized death rates. RESULTS: Trends in the gradient exhibited a few subtle regional differences. Among women, the gradient was often narrowest in the Northeast. The region's distinction grew over time mainly because low-educated women in the Northeast did not experience a significant increase in mortality like their counterparts in other regions (particularly for White women). Among White men, the gradient narrowed to a small degree in the West. CONCLUSIONS: The subtle regional differences indicate that geographic context can accentuate or suppress trends in the gradient. Studies of smaller areas may provide insights into the specific contextual characteristics (e.g., state tax policies) that have shaped the trends, and thus help explain and reverse the widening mortality disparities among US adults. PMID- 24228660 TI - Disparities in diabetes: the nexus of race, poverty, and place. AB - OBJECTIVES: We sought to determine the role of neighborhood poverty and racial composition on race disparities in diabetes prevalence. METHODS: We used data from the 1999-2004 National Health and Nutrition Examination Survey and 2000 US Census to estimate the impact of individual race and poverty and neighborhood racial composition and poverty concentration on the odds of having diabetes. RESULTS: We found a race-poverty-place gradient for diabetes prevalence for Blacks and poor Whites. The odds of having diabetes were higher for Blacks than for Whites. Individual poverty increased the odds of having diabetes for both Whites and Blacks. Living in a poor neighborhood increased the odds of having diabetes for Blacks and poor Whites. CONCLUSIONS: To address race disparities in diabetes, policymakers should address problems created by concentrated poverty (e.g., lack of access to reasonably priced fruits and vegetables, recreational facilities, and health care services; high crime rates; and greater exposures to environmental toxins). Housing and development policies in urban areas should avoid creating high-poverty neighborhoods. PMID- 24228661 TI - Effect of weatherization combined with community health worker in-home education on asthma control. AB - OBJECTIVES: We assessed the benefits of adding weatherization-plus-health interventions to an in-home, community health worker (CHW) education program on asthma control. METHODS: We used a quasi-experimental design to compare study group homes (n = 34) receiving CHW education and weatherization-plus-health structural interventions with historical comparison group homes (n = 68) receiving only education. Data were collected in King County, Washington, from October 2009 to September 2010. RESULTS: Over the 1-year study period, the percentage of study group children with not-well-controlled or very poorly controlled asthma decreased more than the comparison group percentage (100% to 28.8% vs 100% to 51.6%; P = .04). Study group caregiver quality-of-life improvements exceeded comparison group improvements (P = .002) by 0.7 units, a clinically important difference. The decrease in study home asthma triggers (evidence of mold, water damage, pests, smoking) was marginally greater than the comparison group decrease (P = .089). Except for mouse allergen, the percentage of study group allergen floor dust samples at or above the detection limit decreased, although most reductions were not statistically significant. CONCLUSIONS: Combining weatherization and healthy home interventions (e.g., improved ventilation, moisture and mold reduction, carpet replacement, and plumbing repairs) with CHW asthma education significantly improves childhood asthma control. PMID- 24228662 TI - Overcoming inertia: increasing public health departments' access to evidence based information and promoting usage to inform practice. AB - In 2010, the New England Region-National Network of Libraries of Medicine at University of Massachusetts Medical School received funding to improve information access for public health departments in 6 New England states and Colorado. Public health departments were provided with desktop digital access to licensed e-resources available through special pricing. In January through mid April 2012, we evaluated the effectiveness of providing access to and training for using e-resources to public health department staff to motivate usage in practice. We found that additional strategies are needed to accomplish this. PMID- 24228663 TI - The adoption and discontinuation of clinical services by local health departments. AB - OBJECTIVES: We identified factors associated with local health department (LHD) adoption and discontinuation of clinical services. METHODS: We used multivariate regression with 1997 and 2008 LHD survey and area resource data to examine factors associated with LHDs maintaining or offering more clinical services (adopter) versus offering fewer services (discontinuer) over time and with the number of clinical services discontinued among discontinuers. RESULTS: Few LHDs (22.2%) were adopters. The LHDs were more likely to be adopters if operating in jurisdictions with local boards of health and not in health professional shortage areas, and if experiencing larger percentage increase in non-White population and Medicaid managed care penetration. Discontinuer LHDs eliminated more clinical services in jurisdictions that decreased core public health activities' scope over time, increased community partners' involvement in these activities, had larger increases in Medicaid managed care penetration, and had lower LHD expenditures per capita over time. CONCLUSIONS: Most LHDs are discontinuing clinical services over time. Those that cover a wide range of core public health functions are less likely to discontinue services when residents lack care access. Thus, the impact of discontinuation on population health may be mitigated. PMID- 24228664 TI - Public health in action. PMID- 24228665 TI - Question context, ethnic difference, and self-rated health. PMID- 24228666 TI - Tobacco use screening and treatment by outpatient psychiatrists before and after release of the American Psychiatric Association treatment guidelines for nicotine dependence. AB - OBJECTIVES: We examined tobacco use screening and treatment by US psychiatrists before and after release of the 1996 American Psychiatric Association (APA) nicotine dependence treatment guidelines. METHODS: We used data from the National Ambulatory Medical Care Survey to identify rates of tobacco screening and treatment by psychiatrists before the release of the guidelines (1993-1996) and during 2 postguidelines periods: 2001-2005 and 2006-2010. Multiple logistic regression was used to compare preguidelines and postguidelines rates. RESULTS: Psychiatrists screened for tobacco use during 77% of visits from 1993 to 1996, 69% of visits from 2001 to 2005 (odds ratio [OR] = 0.69; 95% confidence interval [CI] = 0.64, 0.75), and 60% of visits from 2006 to 2010 (OR = 0.46; 95% CI = 0.43, 0.50). Psychiatrists provided cessation counseling to 12% of smokers from 1993 to 1996, 11% from 2001 to 2005 (OR = 0.97; 95% CI = 0.74, 1.26), and 23% from 2006 to 2010 (OR = 2.23; 95% CI = 1.74, 2.86). Psychiatrists prescribed nicotine replacement therapy to fewer than 1% of smokers during all 3 time periods. CONCLUSIONS: Psychiatrists are screening for tobacco use at declining rates, and the proportion of smokers provided with treatment remains low. PMID- 24228667 TI - Regulating alcohol advertising: content analysis of the adequacy of federal and self-regulation of magazine advertisements, 2008-2010. AB - OBJECTIVES: We analyzed beer, spirits, and alcopop magazine advertisements to determine adherence to federal and voluntary advertising standards. We assessed the efficacy of these standards in curtailing potentially damaging content and protecting public health. METHODS: We obtained data from a content analysis of a census of 1795 unique advertising creatives for beer, spirits, and alcopops placed in nationally available magazines between 2008 and 2010. We coded creatives for manifest content and adherence to federal regulations and industry codes. RESULTS: Advertisements largely adhered to existing regulations and codes. We assessed only 23 ads as noncompliant with federal regulations and 38 with industry codes. Content consistent with the codes was, however, often culturally positive in terms of aspirational depictions. In addition, creatives included degrading and sexualized images, promoted risky behavior, and made health claims associated with low-calorie content. CONCLUSIONS: Existing codes and regulations are largely followed regarding content but do not adequately protect against content that promotes unhealthy and irresponsible consumption and degrades potentially vulnerable populations in its depictions. Our findings suggest further limitations and enhanced federal oversight may be necessary to protect public health. PMID- 24228668 TI - Statewide pandemic influenza vaccination reminders for children with chronic conditions. AB - OBJECTIVES: We evaluated the use of a statewide immunization information system (IIS) to target influenza vaccine reminders to high-risk children during a pandemic. METHODS: We used Michigan's IIS to identify high-risk children (i.e., those with >= 1 chronic condition) aged 6 months to 18 years with no record of pH1N1 vaccination among children currently or previously enrolled in Medicaid (n = 202,133). Reminders were mailed on December 7, 2009. We retrospectively assessed children's eligibility for evaluation and compared influenza vaccination rates across 3 groups on the basis of their high-risk and reminder status. RESULTS: Of the children sent reminders, 53,516 were ineligible. Of the remaining 148,617 children, vaccination rates were higher among the 142,383 high-risk children receiving reminders than among the 6234 high-risk children with undeliverable reminders and the 142,383 control group children without chronic conditions who were not sent reminders. CONCLUSIONS: Midseason reminders to parents of unvaccinated high-risk children with current or past Medicaid enrollment were associated with increased pH1N1 and seasonal influenza vaccination rates. Future initiatives should consider strategies to expand targeting of high-risk groups and improve IIS reporting during pandemic events. PMID- 24228669 TI - The effects of misclassification biases on veteran suicide rate estimates. AB - OBJECTIVES: We assessed the impact that possible veteran suicide misclassification biases (i.e., inaccuracy in ascertainment of veteran status on the death certificate and misclassification of suicide as other manner of death) have on veteran suicide rate estimates. METHODS: We obtained suicide mortality data from the 2003-2010 National Violent Death Reporting System and the 2003-2010 Department of Defense Casualty Analysis System. We derived population estimates from the 2003-2010 American Community Survey and 2003-2010 Department of Veterans Affairs data. We computed veteran and nonveteran suicide rates. RESULTS: The results showed that suicide rates were minimally affected by the adjustment for the misclassification of current military personnel suicides as veterans. Moreover, combining suicides and deaths by injury of undetermined intent did not alter the conclusions. CONCLUSIONS: The National Violent Death Reporting System is a valid surveillance system for veteran suicide. However, more than half of younger (< 25 years) male and female suicides, labeled as veterans, were likely to have been current military personnel at the time of their death and misclassified on the death certificate. PMID- 24228670 TI - Increasing hand washing compliance with a simple visual cue. AB - We tested the efficacy of a simple, visual cue to increase hand washing with soap and water. Automated towel dispensers in 8 public bathrooms were set to present a towel either with or without activation by users. We set the 2 modes to operate alternately for 10 weeks. Wireless sensors were used to record entry into bathrooms. Towel and soap consumption rates were checked weekly. There were 97,351 hand-washing opportunities across all restrooms. Towel use was 22.6% higher (P=.05) and soap use was 13.3% higher (P=.003) when the dispenser presented the towel without user activation than when activation was required. Results showed that a visual cue can increase hand-washing compliance in public facilities. PMID- 24228671 TI - Lee and Schwarz respond. PMID- 24228672 TI - Design of implementation studies for quality improvement programs: an effectiveness-cost-effectiveness framework. AB - Translational research applies basic science discoveries in clinical and community settings. Implementation research is often limited by tremendous variability among settings; therefore, generalization of findings may be limited. Adoption of a novel procedure in a community practice is usually a local decision guided by setting-specific knowledge. The conventional statistical framework that aims to produce generalizable knowledge is inappropriate for local quality improvement investigations. We propose an analytic framework based on cost effectiveness of the implementation study design, taking into account prior knowledge from local experts. When prior knowledge does not indicate a clear preference between the new and standard procedures, local investigation should guide the choice. The proposed approach requires substantially smaller sample sizes than the conventional approach. Sample size formulae and general guidance are provided. PMID- 24228673 TI - Impact of paid sick leave policy: a social planner's perspective. PMID- 24228674 TI - Rethinking public health: promoting public engagement through a new discursive environment. AB - I reexamine the notion of public health after reviewing critiques of the prevalent individualistic conception of health. I argue that public health should mean not only the health of the public but also health in the public and by the public, and I expound on the social contingency of health and highlight the importance of the interpersonal dimensions of health conditions and health promotion efforts. Promoting public health requires activating health-enhancing communicative behaviors (such as interpersonal advocacy and mutual responsibility taking) in addition to individual behavioral change. To facilitate such communicative behaviors, it is imperative to first construct a new discursive environment in which to think and talk about health in a language of interdependence and collective efforts. PMID- 24228675 TI - Cigarettes become a dangerous product: tobacco in the rearview mirror, 1952-1965. AB - Tobacco control's unparalleled success comes partly from advocates broadening the focus of responsibility beyond the smoker to include industry and government. To learn how this might apply to other issues, we examined how early tobacco control events were framed in news, legislative testimony, and internal tobacco industry documents. Early debate about tobacco is stunning for its absence of the personal responsibility rhetoric prominent today, focused instead on the health harms from cigarettes. The accountability of government, rather than the industry or individual smokers, is mentioned often; solutions focused not on whether government had a responsibility to act, but on how to act. Tobacco lessons can guide advocates fighting the food and beverage industry, but must be reinterpreted in current political contexts. PMID- 24228676 TI - Extending public health: the Rockefeller Sanitary Commission and hookworm in the American South. AB - The Rockefeller Sanitary Commission for the Eradication of Hookworm Disease (1909 1914) fielded a philanthropic public health project that had three goals: to estimate hookworm prevalence in the American South, provide treatment, and eradicate the disease. Activities covered 11 Southern states, and Rockefeller teams found that about 40% of the population surveyed was infected. However, the commission met strong resistance and lacked the time and resources to achieve universal county coverage and meet project goals. We explore how these constraints triggered project changes that systematically reshaped project operations and the characteristics of the counties surveyed and treated. We show that county selectivity reduced the project's initial potential to affect hookworm prevalence estimates, treatment, and eradication in the American South. PMID- 24228677 TI - Evidence, power, and policy change in community-based participatory research. AB - Meaningful improvements in health require modifying the social determinants of health. As policies are often underlying causes of the living conditions that shape health, policy change becomes a health goal. This focus on policy has led to increasing interest in expanding the focus of community-based participatory research (CBPR) to change not only communities but also policies. To best realize this potential, the relationship between evidence and power in policy change must be more fully explored. Effective action to promote policies that improve population health requires a deeper understanding of the roles of scientific evidence and political power in bringing about policy change; the appropriate scales for policy change, from community to global; and the participatory processes that best acknowledge the interplay between power and evidence. PMID- 24228678 TI - Big publishing and the economics of competition. PMID- 24228679 TI - Important considerations when analyzing health survey data collected using a complex sample design. AB - Researchers often use survey data to answer important public health policy questions. Examples of common data sources used in public health research include the National Health and Nutrition Examination Survey, the National Health Interview Survey, the Medical Expenditure Panel Survey, and the National Ambulatory Medical Care Survey. All these surveys employ a complex sample design to recruit participants into the survey. When performing secondary analyses of complex sample survey data, it is necessary to remind ourselves of the key features of these designs that must be taken into account to produce valid statistical estimates. PMID- 24228680 TI - Creating quality improvement culture in public health agencies. AB - OBJECTIVES: We conducted case studies of 10 agencies that participated in early quality improvement efforts. METHODS: The agencies participated in a project conducted by the National Association of County and City Health Officials (2007 2008). Case study participants included health directors and quality improvement team leaders and members. We implemented multiple qualitative analysis processes, including cross-case analysis and logic modeling. We categorized agencies according to the extent to which they had developed a quality improvement culture. RESULTS: Agencies were conducting informal quality improvement projects (n = 4), conducting formal quality improvement projects (n = 3), or creating a quality improvement culture (n = 4). Agencies conducting formal quality improvement and creating a quality improvement culture had leadership support for quality improvement, participated in national quality improvement initiatives, had a greater number of staff trained in quality improvement and quality improvement teams that met regularly with decision-making authority. Agencies conducting informal quality improvement were likely to report that accreditation is the major driver for quality improvement work. Agencies creating a quality improvement culture were more likely to have a history of evidence-based decision making and use quality improvement to address emerging issues. CONCLUSIONS: Our findings support previous research and add the roles of national public health accreditation and emerging issues as factors in agencies' ability to create and sustain a quality improvement culture. PMID- 24228681 TI - Work in multiple jobs and the risk of injury in the US working population. AB - OBJECTIVES: We compared the risk of injury for multiple job holders (MJHs) with that for single job holders (SJHs). METHODS: We used information from the National Health Interview Survey for the years 1997 through 2011 to estimate the rate of multiple job holding in the United States and compared characteristics and rates of self-reported injury (work and nonwork) for SJHs versus MJHs. RESULTS: Approximately 8.4% of those employed reported working more than 1 job in the week before the interview. The rate of work and nonwork injury episodes per 100 employed workers was higher for MJHs than for SJHs (4.2; 95% confidence interval [CI] = 3.5, 4.8; vs 3.3; 95% CI = 3.1, 3.5 work injuries and 9.9; 95% CI = 8.9, 10.9; vs 7.4; 95% CI = 7.1, 7.6 nonwork injuries per 100 workers, respectively). When calculated per 100 full-time equivalents (P < .05), the rate ratio remained higher for MJHs. CONCLUSIONS: Our findings suggest that working in multiple jobs is associated with an increased risk of an injury, both at work and not at work, and should be considered in injury surveillance. PMID- 24228682 TI - MPH education for the 21st century: design of Columbia University's new public health curriculum. AB - Because public health challenges are changing rapidly, over the past 3 years, we have turned a critical eye to the master of public health program at the Columbia University Mailman School of Public Health. Under a process dubbed "curriculum renewal," we engaged more than 170 faculty, staff, and students (and hundreds of alumni and employers of our graduates) in an initiative to develop a completely new design for master of public health education that launched in fall 2012. We have described its design and structure and presented some preliminary evaluation data. PMID- 24228683 TI - The impact of school water, sanitation, and hygiene interventions on the health of younger siblings of pupils: a cluster-randomized trial in Kenya. AB - OBJECTIVES: We examined the impact of school water, sanitation, and hygiene (WASH) interventions on diarrhea-related outcomes among younger siblings of school-going children. METHODS: We conducted a cluster-randomized trial among 185 schools in Kenya from 2007 to 2009. We assigned schools to 1 of 2 study groups according to water availability. Multilevel logistic regression models, adjusted for baseline measures, assessed differences between intervention and control arms in 1-week period prevalence of diarrhea and 2-week period prevalence of clinic visits among children younger than 5 years with at least 1 sibling attending a program school. RESULTS: Among water-scarce schools, comprehensive WASH improvements were associated with decreased odds of diarrhea (odds ratio [OR] = 0.44; 95% confidence interval [CI] = 0.27, 0.73) and visiting a clinic (OR = 0.36; 95% CI = 0.19, 0.68), relative to control schools. In our separate study group of schools with greater water availability, school hygiene promotion and water treatment interventions and school sanitation improvements were not associated with differences in diarrhea prevalence between intervention and control schools. CONCLUSIONS: In water-scarce areas, school WASH interventions that include robust water supply improvements can reduce diarrheal diseases among young children. PMID- 24228684 TI - Description of a school nurse visit syndromic surveillance system and comparison to emergency department visits, New York City. AB - OBJECTIVES: We compared school nurse visit syndromic surveillance system data to emergency department (ED) visit data for monitoring illness in New York City schoolchildren. METHODS: School nurse visit data recorded in an electronic health record system are used to conduct daily surveillance of influenza-like illness, fever-flu, allergy, asthma, diarrhea, and vomiting syndromes. We calculated correlation coefficients to compare the percentage of syndrome visits to the school nurse and ED for children aged 5 to 14 years, from September 2006 to June 2011. RESULTS: Trends in influenza-like illness correlated significantly (correlation coefficient = 0.89; P < .001) and 72% of school signals occurred on days that ED signaled. Trends in allergy (correlation coefficient = 0.73; P < .001) and asthma (correlation coefficient = 0.56; P < .001) also correlated and school signals overlapped with ED signals on 95% and 51% of days, respectively. Substantial daily variation in diarrhea and vomiting visits limited our ability to make comparisons. CONCLUSIONS: Compared with ED syndromic surveillance, the school nurse system identified similar trends in influenza-like illness, allergy, and asthma syndromes. Public health practitioners without school-based surveillance may be able to use age-specific analyses of ED syndromic surveillance data to monitor illness in schoolchildren. PMID- 24228685 TI - Complete mitochondrial genome of a chipmunk species, Tamias sibiricus (Rodentia: Sciuridae) in Korea. AB - We sequenced the complete mitochondrial genome (KF668525) of Tamias sibiricus in South Korea. The mitogenome of the Korean chipmunk T. sibiricus was 16,558 bp long with base composition of 33.8% A, 31.1% T, 22.9% C and 12.2% G. Total nucleotide similarity of T. sibiricus and Marmota himalayana (JX069958) genomes was 80.4% ranging from 66.9% (D-loop region) to 97.3% (tRNA(Leu)((CUN))). The present study will contribute to understanding taxonomic status and genetic divergence of Northeast Asian T. sibiricus populations. PMID- 24228686 TI - Significant population genetic structure detected in the small yellow croaker Larimichthys polyactis inferred from mitochondrial control region. AB - The population genetic structure of the small yellow croaker (Larimichthys polyactis) between China and Korea was further estimated by broad-scale sampling locations (Gulf of Bohai, Yellow Sea including Korea). One hundred and seventeen individuals from eight localities from coastal waters of China and Korea were analyzed based on mtDNA control region sequences (5' mtDNA CR). A total of 97 polymorphic sites were checked, which defined 136 haplotypes. A pattern with high levels of haplotype diversity (h=0.994 +/- 0.002) and nucleotide diversity (l=0.020 +/- 0.010) was detected in the examined range, and the genetic diversity of Korea populations was higher than that of China populations. Population genetic structure analyses (MDS, AMOVA, Fst, Barrier) showed that significant genetic differentiation existed between China and Korea populations. The migration analysis indicated asymmetry migration also existed among populations, which was consistent with the result of population genetic structure. Using a variety of phylogenetic methods, coalescent reasoning, and molecular dating interpreted in conjunction with paleoclimateic and physiographic evidence, we inferred that the genetic make-up of extant populations of L. polyactis was shaped by Pleistocene environmental impacts on the historical demography of this species. Coalescent analyses (Neutrality tests, Mismatch distribution analysis, Bayesian skyline analyses) showed that the species along coastline of China and Korea has experienced population expansions originated in its most recent history at about 32-196 kya and 166-662 kya before present, respectively. PMID- 24228687 TI - Multivariable analysis of the association between fathers' and youths' physical activity in the United States. AB - BACKGROUND: Although the benefits of physical activity have been well established, a significant number of children and adolescents in the U.S. do not meet the recommended levels of daily physical activity. Parental influences such as parents' physical activity participation may play an important role in affecting youths' physical activity. METHODS: This study used the Child Development Supplement of the Panel Study of Income Dynamics to examine the associations between fathers' vigorous physical activity (VPA) and VPA participation (>0 day(s)/week) and frequency (days/week) of 887 youths aged 10 through 18 based on a nationally representative sample of families in the US. Logistic and negative binomial regression analyses were used to examine the association between past frequency (times/week) and an indicator of recommended (>=3 times/week) frequency of father's VPA and youth's VPA participation and youths' VPA frequency, respectively. We examined the sensitivity to the inclusion of various youth, family, mother's VPA, and contextual control measures. Analyses also were undertaken by gender. RESULTS: Father's past VPA frequency was positively associated with both youths' VPA participation and with youths' VPA frequency for the full and female samples of youths, even after the inclusion of demographic, socio-economic, and local area characteristics. Father's past recommended VPA frequency was positively associated with youths' VPA participation in the full sample only and with youths' VPA frequency in the female sub-sample only. Simulation results showed that an increase in father's past weekly VPA frequency from zero to the minimum recommended level (three times per week) was associated with an increased predicted probability of youths' weekly VPA participation from approximately 67% to 74% for the full sample (61% to 73% for females and 74% to 77% for males). CONCLUSION: The results from this study suggest that environmental and/or family based interventions that increase fathers' VPA may help improve youths' VPA. PMID- 24228688 TI - Trait and state anxiety: relations to executive functioning in an at-risk sample. AB - Prior research with adults suggests mixed evidence for the relations of state and trait anxiety to prefrontal executive functions (EF). Trait anxiety is hypothesised to impair the efficiency of prefrontal areas and goal-directed attention and has been largely associated with poorer performance on executive functioning tasks. Fewer studies have investigated state anxiety, and the findings have been mixed. As studies of these processes in children have been limited by small sample sizes and a focus on working memory, we examine whether state and trait anxiety are associated with performance on two EF tasks in a sample of urban, low-income children, ages 9-12. Results indicated that higher trait anxiety predicted lower executive functioning on both tasks. In addition, higher state anxiety was related to better performance on the Stroop task. Results demonstrate that, consistent with the adult literature, higher trait anxiety is related to lower executive functioning in children. PMID- 24228689 TI - Systems metabolic engineering of Corynebacterium glutamicum for production of the chemical chaperone ectoine. AB - BACKGROUND: The stabilizing and function-preserving effects of ectoines have attracted considerable biotechnological interest up to industrial scale processes for their production. These rely on the release of ectoines from high-salinity cultivated microbial producer cells upon an osmotic down-shock in rather complex processor configurations. There is growing interest in uncoupling the production of ectoines from the typical conditions required for their synthesis, and instead design strains that naturally release ectoines into the medium without the need for osmotic changes, since the use of high-salinity media in the fermentation process imposes notable constraints on the costs, design, and durability of fermenter systems. RESULTS: Here, we used a Corynebacterium glutamicum strain as a cellular chassis to establish a microbial cell factory for the biotechnological production of ectoines. The implementation of a mutant aspartokinase enzyme ensured efficient supply of L-aspartate-beta-semialdehyde, the precursor for ectoine biosynthesis. We further engineered the genome of the basic C. glutamicum strain by integrating a codon-optimized synthetic ectABCD gene cluster under expressional control of the strong and constitutive C. glutamicum tuf promoter. The resulting recombinant strain produced ectoine and excreted it into the medium; however, lysine was still found as a by-product. Subsequent inactivation of the L-lysine exporter prevented the undesired excretion of lysine while ectoine was still exported. Using the streamlined cell factory, a fed-batch process was established that allowed the production of ectoine with an overall productivity of 6.7 g L(-1) day(-1) under growth conditions that did not rely on the use of high-salinity media. CONCLUSIONS: The present study describes the construction of a stable microbial cell factory for recombinant production of ectoine. We successfully applied metabolic engineering strategies to optimize its synthetic production in the industrial workhorse C. glutamicum and thereby paved the way for further improvements in ectoine yield and biotechnological process optimization. PMID- 24228690 TI - Inhibition of microtubule assembly by a complex of actin and antitumor macrolide aplyronine A. AB - Aplyronine A (ApA) is a marine natural product that shows potent antitumor activity. While both ApA and ApC, a derivative of ApA that lacks a trimethylserine ester moiety, inhibit actin polymerization in vitro to the same extent, only ApA shows potent cytotoxicity. Therefore, the molecular targets and mechanisms of action of ApA in cells have remained unclear. We report that ApA inhibits tubulin polymerization in a hitherto unprecedented way. ApA forms a 1:1:1 heterotrimeric complex with actin and tubulin, in association with actin synergistically binding to tubulin, and inhibits tubulin polymerization. Tubulin targeting agents have been widely used in cancer chemotherapy, but there are no previous descriptions of microtubule inhibitors that also bind to actin and affect microtubule assembly. ApA inhibits spindle formation and mitosis in HeLa S3 cells at 100 pM, a much lower concentration than is needed for the disassembly of the actin cytoskeleton. The results of the present study indicate that ApA represents a rare type of natural product, which binds to two different cytoplasmic proteins to exert highly potent biological activities. PMID- 24228691 TI - Q&A: Cognitive ethology - inside the minds of other species. PMID- 24228692 TI - Analysis of Sry duplications on the Rattus norvegicus Y-chromosome. AB - BACKGROUND: Gene copy number variation plays a large role in the evolution of genomes. In Rattus norvegicus and other rodent species, the Y-chromosome has accumulated multiple copies of Sry loci. These copy number variations have been previously linked with changes in phenotype of animal models such as the spontaneously hypertensive rat (SHR). This study characterizes the Y-chromosome in the Sry region of Rattus norvegicus, while addressing functional variations seen in the Sry protein products. RESULTS: Eleven Sry loci have been identified in the SHR with one (nonHMG Sry) containing a frame shift mutation. The nonHMGSry is found and conserved in the related WKY and SD rat strains. Three new, previously unidentified, Sry loci were identified in this study (Sry3BII, Sry4 and Sry4A) in both SHR and WKY. Repetitive element analysis revealed numerous LINE-L1 elements at regions where conservation is lost among the Sry copies. In addition we have identified a retrotransposed copy of Med14 originating from spliced mRNA, two autosomal genes (Ccdc110 and HMGB1) and a normal mammalian Y chromosome gene (Zfy) in the Sry region of the rat Y-chromosome. Translation of the sequences of each Sry gene reveals eight proteins with amino acid differences leading to changes in nuclear localization and promoter activation of a Sry responsive gene. Sry-beta (coded by the Sry2 locus) has an increased cytoplasmic fraction due to alterations at amino acid 21. Sry-gamma has altered gene regulation of the Sry1 promoter due to changes at amino acid 76. CONCLUSIONS: The duplication of Sry on the Rattus norvegicus Y-chromosome has led to proteins with altered functional ability that may have been selected for functions in addition to testis determination. Additionally, several other genes not normally found on the Y-chromosome have duplicated new copies into the region around the Sry genes. These suggest a role of active transposable elements in the evolution of the mammalian Y-chromosome in species such as Rattus norvegicus. PMID- 24228693 TI - Role of beta/delta101Gln in regulating the effect of temperature and allosteric effectors on oxygen affinity in woolly mammoth hemoglobin. AB - The oxygen affinity of woolly mammoth hemoglobin (rHb WM) is less affected by temperature change than that of Asian elephant hemoglobin (rHb AE) or human normal adult hemoglobin (Hb A). We report here a biochemical-biophysical study of Hb A, rHb AE, rHb WM, and three rHb WM mutants with amino acid substitutions at beta/delta101 (beta/delta101Gln->Glu, Lys, or Asp) plus a double and a triple mutant, designed to clarify the role of the beta/delta101 residue. The beta/delta101Gln residue is important for responding to allosteric effectors, such as phosphate, inositol hexaphosphate (IHP), and chloride. The rHb WM mutants studied generally have higher affinity for oxygen under various conditions of pH, temperature, and salt concentration, and in the presence or absence of organic phosphate, than do rHb WM, rHb AE, and Hb A. Titrations for the O2 affinity of these mutant rHbs as a function of chloride concentration indicate a lower heterotopic effect of this anion due to the replacement of beta/delta101Gln in rHb WM. The alkaline Bohr effect of rHb WM and its mutants is reduced by 20-50% compared to that of Hb A and is independent of changes in temperature, in contrast to what has been observed in the hemoglobins of most mammalian species, including human. The results of our study on the temperature dependence of the O2 affinity of rHb WM and its mutant rHbs illustrate the important role of beta/delta101Gln in regulating the functional properties of these hemoglobins. PMID- 24228694 TI - Phylogeographic analysis of the true lemurs (genus Eulemur) underlines the role of river catchments for the evolution of micro-endemism in Madagascar. AB - INTRODUCTION: Due to its remarkable species diversity and micro-endemism, Madagascar has recently been suggested to serve as a biogeographic model region. However, hypothesis-based tests of various diversification mechanisms that have been proposed for the evolution of the island's micro-endemic lineages are still limited. Here, we test the fit of several diversification hypotheses with new data on the broadly distributed genus Eulemur using coalescent-based phylogeographic analyses. RESULTS: Time-calibrated species tree analyses and population genetic clustering resolved the previously polytomic species relationships among eulemurs. The most recent common ancestor of eulemurs was estimated to have lived about 4.45 million years ago (mya). Divergence date estimates furthermore suggested a very recent diversification among the members of the "brown lemur complex", i.e. former subspecies of E. fulvus, during the Pleistocene (0.33-1.43 mya). Phylogeographic model comparisons of past migration rates showed significant levels of gene flow between lineages of neighboring river catchments as well as between eastern and western populations of the redfronted lemur (E. rufifrons). CONCLUSIONS: Together, our results are concordant with the centers of endemism hypothesis (Wilme et al. 2006, Science 312:1063-1065), highlight the importance of river catchments for the evolution of Madagascar's micro-endemic biota, and they underline the usefulness of testing diversification mechanisms using coalescent-based phylogeographic methods. PMID- 24228695 TI - Off-clamp versus complete hilar control partial nephrectomy for renal cell carcinoma: a systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the safety, efficacy, and potential advantages of off clamp partial nephrectomy (OFF-PN) compared with on-clamp partial nephrectomy (ON PN). METHODS: Relevant studies comparing the safety and efficacy of OFF-PN to ON PN were identified through a literature search using MEDLINE, EMBASE, and the Cochrane Library. The outcome measures included baseline characteristics, primary outcomes, and secondary outcomes. RESULTS: Ten retrospective studies (728 cases and 1267 controls) were included. No significant differences between the two groups were detected in any of the baseline variables (age: p=0.19; sex: p=0.49; BMI: p=0.29; tumor size: p=0.44, pre-eGFR: p=0.78) except for tumor location (p<0.001). The OFF-PN group had a higher blood transfusion rate (odds ratio [OR] 1.54, 95% confidence interval [CI] 10.7-2.21, p=0.02), a lower postoperative complication rate (OR 0.61, 95% CI 0.44-0.83, p=0.002), and a lower positive margin rate (OR 0.49, 95% CI 0.26-0.90, p=0.02) than ON-PN. OFF-PN offered a better preservation of renal function than ON-PN (p=0.005). No significant differences were detected between the two groups in other outcomes of interest. In sensitivity analysis, there was no change in the significance of any of the outcomes except for postoperative complication rate (OR 0.91, 95% CI 0.53-1.5, p=0.73) and positive margin rate (OR 0.55, 95% CI 0.25-1.23, p=0.15). CONCLUSIONS: This meta-analysis suggests that with appropriate patient selection, OFF-PN offer comparable perioperative safety, equivalent oncologic outcomes, and superior long-term renal function preservation when compared with ON-PN for renal cell carcinoma. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm our findings. PMID- 24228697 TI - Isostructural nuclear and luminescent probes derived from stabilized [2 + 1] rhenium(I)/technetium(I) organometallic complexes. AB - A convenient method to prepare (99m)Tc analogues of a class of rhenium(I) luminophores was developed, creating isostructural pairs of nuclear and optical probes. A two-step procedure and a new one-pot procedure were used to produce a series of [2 + 1] complexes of the type [Tc(CO)3(bipy)L](+) in greater than 80% yield. The plasma stability of the reported compounds was evaluated, where the basicity of the monodentate pyridine type ligand (L) has a significant impact with half-lives ranging from 2 to 20 h. The ability to generate the radioactive complexes makes it possible to quantitate cell uptake of Re luminophores, which was demonstrated in MCF-7 breast cancer cells using (99m)Tc analogues of two Re(I)-based mitochondrial targeting dyes. PMID- 24228698 TI - OMICS-based personalized oncology: if it is worth doing, it is worth doing well! AB - The era of Personalized Medicine implies getting the right treatment to the right patient at the right schedule and dose at the right time. Tumor biomarker tests are keys to accomplishing this goal successfully. However, much of the translational research regarding tumor biomarker tests has been haphazard, often using data and specimen sets of convenience and ignoring many of the principles of the scientific method. In papers published simultaneously in BMC Medicine and Nature, McShane and colleagues have proposed a checklist of criteria that should be followed by investigators planning to conduct prospective clinical trials directed towards generating high levels of evidence to demonstrate whether a tumor biomarker test has clinical utility for a specific context. These criteria were generated in response to a roadmap reported by a committee convened by the U.S. Institute of Medicine for generation of omics-based biomarker tests. Taken together with several other initiatives to increase the rigor of tumor biomarker research, these criteria will increase the perception of value for tumor biomarker test research and application in the clinic. Please see related article: http://www.biomedcentral.com/1741-7015/11/220. PMID- 24228699 TI - Survey of the prevalence of sexual dysfunctions in Kurdish women. AB - This study evaluates the prevalence of female sexual dysfunctions among Kurdish women. Participants in the study were 196 women between 15 and 55 years of age who attended the gynecological clinic of Be'sat Hospital in Sanandaj Province, Iran. The authors collected relevant data using the Female Sexual Function Index. The mean score was 22.71 (SD = 5). Using a cutoff score of 26.55, the authors found that 151 women (77%) had some sexual dysfunction. Scores declined as patients' age increased; further, an older age at marriage was associated with a higher score. This study, the first about sexual dysfunctions in Kurdish society, shows that sexual dysfunctions are prevalent among women of this ethnicity. Clinicians should complete further studies to assess the factors contributing to this phenomenon. PMID- 24228700 TI - Deeper Processing Is Associated With Support for Policies to Reduce Obesity. AB - Health communication researchers have become increasingly interested in factors that predict support for health-related policy. Previous studies have shown that judgments about issues that are influenced by political ideology can be modified by the depth with which receivers process messages related to that issue. In this study, we test whether the same pattern is found for causal attributions about obesity and, ultimately, support for policies to reduce obesity. A national, random sample of U.S. adults read a story about both individual and societal causes of obesity. The longer the time participants spent on the study, and the more words they generated in a thought-listing procedure (operationalizations of depth of processing), the more likely participants were to support policies to reduce obesity, a traditionally liberal position. The same measures of depth of processing did not influence causal explanation of obesity overall, but the more time political moderates spent on the study, the more likely they were to both attribute societal explanations for obesity's causes and to support policies to combat obesity. We conclude with a discussion of this study's application to health communication campaigns and future research directions. PMID- 24228701 TI - Mailed versus frozen transport of nasal swabs for surveillance of respiratory bacteria in remote Indigenous communities in Australia. AB - BACKGROUND: Surveillance programs and research for acute respiratory infections in remote Australian communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting nasal swabs from a remote setting for bacterial polymerase chain reaction (PCR) testing. METHODS: We sampled every individual who presented to a remote community clinic over a three week period in August at a time of low influenza and no respiratory syncytial virus activity. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for six bacterial species was undertaken using real-time PCR. RESULTS: One hundred and forty participants were enrolled who contributed 150 study visits and paired specimens for testing. Respiratory illnesses accounted for 10% of the reasons for presentation. Bacteria were identified in 117 (78%) presentations for 110 (79.4%) individuals; Streptococcus pneumoniae and Haemophilus influenzae were the most common (each identified in 58% of episodes). The overall sensitivity for any bacterium detected in mailed specimens was 82.2% (95% CI 73.6, 88.1) compared to 94.8% (95% CI 89.4, 98.1) for frozen specimens. The sensitivity of the two methods varied by species identified. CONCLUSION: The mailing of unfrozen nasal specimens from remote communities appears to influence the utility of the specimen for bacterial studies, with a loss in sensitivity for the detection of any species overall. Further studies are needed to confirm our finding and to investigate the possible mechanisms of effect. CLINICAL TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry Number: ACTRN12609001006235. PMID- 24228704 TI - Response to Satter: make the healthy choice the easy choice. PMID- 24228707 TI - Associations between heavy episodic drinking and alcohol related injuries: a case control study. AB - BACKGROUND: Alcohol is a significant risk factor for injuries. This study addresses 1) whether the risk of alcohol related injury increases with frequency of heavy episodic drinking (HED) in a linear fashion, and 2) whether a small group of high risk drinkers accounts for the majority of alcohol related injuries. METHODS: We applied a case - control design. Cases were BAC positive injured patients (n = 534) and controls were respondents to a general population survey in Norway (n = 1947). Age and gender adjusted association between self reported past year HED frequency and alcohol related injury risk was estimated in logistic regression models for all alcohol related injuries and for violence injuries and accident injuries separately. RESULTS: An increase in HED was associated with an increase in risk of alcohol related injury, resembling a linear risk function. The small fraction of high risk drinkers (6.6%) accounted for 41.6% of all alcohol related injuries, thus lending support to the validity of the prevention paradox. CONCLUSION: There is a strong relationship between frequency of heavy episodic drinking and risk of alcohol related injuries, yet the majority of alcohol related injuries are found among drinkers who are not in the high risk group. PMID- 24228708 TI - Prevalence of extended-spectrum beta-lactamase-producing multidrug-resistant Escherichia coli among isolates from community-acquired infections and in silico structural modeling of an ESBL protein. AB - Escherichia coli is a common major cause of bacterial infections in tea tribe patients of the northeast region of Assam, India. In this study, we documented multidrug resistance (MDR) and the prevalence of extended-spectrum beta lactamases (ESBLs) among 148 E. coli strains that were isolated from bacterial infections in tea tribe patients who had a history of self-medication. High prevalence of resistance to ampicillin (82%), amoxicillin (68%), cefixime (60%), norfloxacin (60%), nalidixic acid (60%), and co-trimoxazole (53%) was observed. Of 148 E. coli isolates, 38 (26%) were confirmed as ESBL producers. The ESBL genes were sequenced from highly resistant ESBL producing E. coli isolates. Molecular modeling was performed using MODELLER 9v10 software to determine the three-dimensional structure of a protein. This result indicates that the prevailing reason for the high prevalence of antibiotic resistance in this community is prior exposure to low-quality antibiotics, hence MDR in E. coli is increasing. ESBLs are enzymes that are produced by resistant bacteria that hydrolyze advanced generations of cephalosporin antibiotics and cause resistance, even in patients with community-acquired infections. So our results provide a framework for understanding the structure and possible binding sites of ESBL proteins for drug targeting, and the results were found to be reliable. PMID- 24228709 TI - Parents and children with cerebral palsy discuss communication needs in hospital. AB - OBJECTIVE: The aim of this study was to understand the communication needs and experiences of parents and children with cerebral palsy (CP) and complex communication needs (CCN) in hospital. METHODS: Focus groups with 10 parents and interviews with seven children with CP and CCN were analysed for content themes. RESULTS: Results demonstrated that children often want to communicate directly with hospital staff to: gain attention, answer yes/no, convey basic physical needs, give and receive information, control their environment and participate in preferred activities. Barriers to communication included lack of access to augmentative and alternative communication (AAC), staff preferring to communicate with parents and lack of time to communicate. CONCLUSIONS: Results highlight strategies for successful communication, the role of the parents in supporting communication and provision of AAC systems for children in hospital. Policy and practice implications in the preparation of children with CP and CCN for communication in hospital are discussed. PMID- 24228710 TI - Loss of salmeterol bronchoprotection against exercise in relation to ADRB2 Arg16Gly polymorphism and exhaled nitric oxide. AB - RATIONALE: beta2-Agonists are the treatment of choice for exercise-induced bronchoconstriction (EIB) and act through specific receptors (ADRB2). Arg16Gly polymorphisms have been shown to affect responses to regular use of beta2 agonists. OBJECTIVES: To evaluate the influence of the Arg16Gly receptor polymorphism on salmeterol bronchoprotection in EIB and assess predictors of bronchoprotection. METHODS: A prospective, genotype-blinded, randomized trial was performed in 26 subjects (12 Arg16Arg and 14 Gly16Gly) with EIB who were not on controller therapy. Subjects were administered salmeterol, 50 MUg twice a day for 2 weeks, and underwent an exercise challenge 9 hours after the first and last drug dose. In addition to genotype, FEV1, response to salmeterol, degree of EIB, and exhaled nitric oxide (FE(NO)) at baseline were examined for their association with loss of bronchoprotection (LOB). MEASUREMENTS AND MAIN RESULTS: The maximum exercise-induced FEV1 fall was 27.9 +/- 1.4% during the run-in period, 8.1 +/- 1.2% (70.3 +/- 4.1% bronchoprotection) after the first salmeterol dose, and 22.8 +/- 3.2% (18.9 +/- 11.5% bronchoprotection) after 2 weeks of salmeterol (P = 0.0001). The Arg16Gly polymorphisms were not associated with the LOB in response to salmeterol. FeNO values at baseline were significantly related to the LOB (r = 0.47; P = 0.01). Mean change was a 74 +/- 13% LOB in subjects with FE(NO) levels greater than 50 ppb and a 7 +/- 16% gain in bronchoprotection in those with FE(NO) levels less than 25 ppb (P = 0.01). CONCLUSIONS: The LOB that occurs with chronic long-acting beta2-agonists use is not affected by ADRB2 Arg16Gly polymorphisms. High FE(NO) was associated with marked LOB. Use of long-acting beta2-agonists before achieving a reduction in FeNO may need to be avoided. Clinical trial registered with www.clinicaltrials.gov (NCT 00595361). PMID- 24228711 TI - Wilms' tumour suppressor gene 1 (WT1) is involved in the carcinogenesis of Lung cancer through interaction with PI3K/Akt pathway. AB - ABSRACT: Although studies have shown the oncogene WT1 is overexpressed in lung cancer, there is no data showing the implication of WT1 in lung cancer biology. In the present study, we first demonstrated that isotype C of WT1 was conservely overexpressed in 20 lung cancer patient specimens. Knockdown of WT1 by small interference RNA (siRNA) transfection resulted in a significant inhibition of cell proliferation, induction of cell cycle arrest at G1 phase, and the expression change of BCL-2 family genes in WT1+ A549 cells. Furthermore, we found that DDP treatment could decrease the WT1 mRNA expression level by 5% and 15% at a dose of 1 MUg/ml, by 25% and 40% at a dose of 2 MUg/ml for 24 and 48 h, respectively. In the mean time, DDP treatment also reduced the PI3K/AKT pathway activity. Further analysis by using siRNA targeting the AKT-1 and the PI3K pathway inhibitor Ly294002 revealed that the AKT-1 siRNA reduced the WT1 expression effectively in A549 cells, and the same result was observed in Ly294002 treated cells, indicating that DDP treatment could down regulate WT1 expression through the PI3K/AKT pathway. Of particular interest, knockdown of WT1 also inhibited the AKT expression effectively, Chip assay further confirmed that WT1 is a transcription factor of AKT-1. We thus concluded that there is a positive feedback loop between WT1 and AKT-1. Taken together, DDP treatment downregulates the WT1 expression through the PI3K/AKT signaling pathway, and there is a feedback between WT1 and AKT-1; WT1 is involved in cellular proliferation in A549 cells, WT1 inhibition in combination with DDP will provide a new light for lung cancer therapy. PMID- 24228713 TI - Open questions: genomics and how far we haven't come. PMID- 24228712 TI - Nanosecond time scale motions in proteins revealed by high-resolution NMR relaxometry. AB - Understanding the molecular determinants underlying protein function requires the characterization of both structure and dynamics at atomic resolution. Nuclear relaxation rates allow a precise characterization of protein dynamics at the Larmor frequencies of spins. This usually limits the sampling of motions to a narrow range of frequencies corresponding to high magnetic fields. At lower fields one cannot achieve sufficient sensitivity and resolution in NMR. Here, we use a fast shuttle device where the polarization builds up and the signals are detected at high field, while longitudinal relaxation takes place at low fields 0.5 < B0 < 14.1 T. The sample is propelled over a distance up to 50 cm by a blowgun-like system in about 50 ms. The analysis of nitrogen-15 relaxation in the protein ubiquitin over such a wide range of magnetic fields offers unprecedented insights into molecular dynamics. Some key regions of the protein feature structural fluctuations on nanosecond time scales, which have so far been overlooked in high-field relaxation studies. Nanosecond motions in proteins may have been underestimated by traditional high-field approaches, and slower supra tau(c) motions that have no effect on relaxation may have been overestimated. High-resolution relaxometry thus opens the way to a quantitative characterization of nanosecond motions in proteins. PMID- 24228714 TI - MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. AB - Numerous physiological functions of the pineal gland hormone melatonin are mediated via activation of two G-protein-coupled receptors, MT1 and MT2. The melatonergic drugs on the market, ramelteon and agomelatine, as well as the most advanced drug candidates under clinical evaluation, tasimelteon and TIK-301, are high-affinity nonselective MT1/MT2 agonists. A great number of MT2-selective ligands and, more recently, several MT1-selective agents have been reported to date. Herein, we review recent advances in the field focusing on high-affinity agonists and antagonists and those displaying selectivity toward MT1 and MT2 receptors. Moreover, the existing models of MT1 and MT2 receptors as well as the current status in the emerging field of melatonin receptor oligomerization are critically discussed. In addition to the already existing indications, such as insomnia, circadian sleep disorders, and depression, new potential therapeutic applications of melatonergic ligands including cardiovascular regulation, appetite control, tumor growth inhibition, and neurodegenerative diseases are presented. PMID- 24228715 TI - Transcriptome sequencing and microarray design for functional genomics in the extremophile Arabidopsis relative Thellungiella salsuginea (Eutrema salsugineum). AB - BACKGROUND: Most molecular studies of plant stress tolerance have been performed with Arabidopsis thaliana, although it is not particularly stress tolerant and may lack protective mechanisms required to survive extreme environmental conditions. Thellungiella salsuginea has attracted interest as an alternative plant model species with high tolerance of various abiotic stresses. While the T. salsuginea genome has recently been sequenced, its annotation is still incomplete and transcriptomic information is scarce. In addition, functional genomics investigations in this species are severely hampered by a lack of affordable tools for genome-wide gene expression studies. RESULTS: Here, we report the results of Thellungiella de novo transcriptome assembly and annotation based on 454 pyrosequencing and development and validation of a T. salsuginea microarray. ESTs were generated from a non-normalized and a normalized library synthesized from RNA pooled from samples covering different tissues and abiotic stress conditions. Both libraries yielded partially unique sequences, indicating their necessity to obtain comprehensive transcriptome coverage. More than 1 million sequence reads were assembled into 42,810 unigenes, approximately 50% of which could be functionally annotated. These unigenes were compared to all available Thellungiella genome sequence information. In addition, the groups of Late Embryogenesis Abundant (LEA) proteins, Mitogen Activated Protein (MAP) kinases and protein phosphatases were annotated in detail. We also predicted the target genes for 384 putative miRNAs. From the sequence information, we constructed a 44 k Agilent oligonucleotide microarray. Comparison of same-species and cross species hybridization results showed superior performance of the newly designed array for T. salsuginea samples. The developed microarrays were used to investigate transcriptional responses of T. salsuginea and Arabidopsis during cold acclimation using the MapMan software. CONCLUSIONS: This study provides the first comprehensive transcriptome information for the extremophile Arabidopsis relative T. salsuginea. The data constitute a more than three-fold increase in the number of publicly available unigene sequences and will greatly facilitate genome annotation. In addition, we have designed and validated the first genome wide microarray for T. salsuginea, which will be commercially available. Together with the publicly available MapMan software this will become an important tool for functional genomics of plant stress tolerance. PMID- 24228716 TI - Formal reduction potential of 3,5-difluorotyrosine in a structured protein: insight into multistep radical transfer. AB - The reversible Y-O*/Y-OH redox properties of the alpha3Y model protein allow access to the electrochemical and thermodynamic properties of 3,5 difluorotyrosine. The unnatural amino acid has been incorporated at position 32, the dedicated radical site in alpha3Y, by in vivo nonsense codon suppression. Incorporation of 3,5-difluorotyrosine gives rise to very minor structural changes in the protein scaffold at pH values below the apparent pK (8.0+/-0.1) of the unnatural residue. Square-wave voltammetry on alpha3(3,5)F2Y provides an E degrees '(Y-O*/Y-OH) of 1026+/-4 mV versus the normal hydrogen electrode (pH 5.70+/-0.02) and shows that the fluoro substitutions lower the E degrees ' by 30+/-3 mV. These results illustrate the utility of combining the optimized alpha3Y tyrosine radical system with in vivo nonsense codon suppression to obtain the formal reduction potential of an unnatural aromatic residue residing within a well-structured protein. It is further observed that the protein E degrees ' values differ significantly from peak potentials derived from irreversible voltammograms of the corresponding aqueous species. This is notable because solution potentials have been the main thermodynamic data available for amino acid radicals. The findings in this paper are discussed relative to recent mechanistic studies of the multistep radical-transfer process in Escherichia coli ribonucleotide reductase site-specifically labeled with unnatural tyrosine residues. PMID- 24228718 TI - An insect defensin-derived beta-hairpin peptide with enhanced antibacterial activity. AB - Insect defensins are a class of small, cysteine-rich antimicrobial peptides primarily active on Gram-positive bacteria. Their roles in maggot therapy for treating chronic wound infection have been reported recently. However, a relatively narrow antibacterial spectrum together with the lack of a cost effective means of commercial-scale production has limited their application. To further exploit the therapeutic potential of these molecules, we engineered the carboxyl-terminal beta-sheet of navidefensin2-2, an insect defensin from Nasonia vitripennis, based on its structural similarity to naturally occurring microbicidal beta-hairpin peptides. The designed peptide of 14 residues, referred to as NvBH, spans the beta-sheet region of the defensin with two amino acids substituted for assembly of a disulfide-bonded amphipathic beta-hairpin structure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with circular dichroism (CD) analysis shows that the oxidized NvBH (oNvBH), produced from the synthetic peptide by air oxidization in an alkaline environment, folds into a typical beta-hairpin structure linked by two disulfide bridges (Cys1-Cys4; Cys2-Cys3). However, such a structure appears not to be functionally necessary as synthetic NvBH with a spontaneously oxidized disulfide bridge (Cys2-Cys3) (termed poNvBH) displayed similar antibacterial potency to oNvBH. In comparison with oNvBH, poNvBH exhibited higher serum stability and more resistance on tryptic digestion. These two forms of peptides are capable of killing an array of Gram-positive (including antibiotic-resistant strains of Staphylococcus) and Gram-negative bacterial pathogens at low micromolar concentrations through a membrane disruptive mode of action. Our work indicates that the beta-sheet region of insect defensins is a promising subdomain of proteins in anti-infective drug discovery. PMID- 24228717 TI - Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons. AB - BACKGROUND: Amitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present. RESULTS: Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manner and had an IC50 of 15.16 MUM in acute isolated trigeminal ganglion (TG) neurons of the rats. 10 MUM AMI significantly shifted the steady-state inactivation of Nav1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 MUM AMI caused a use-dependent blockade of Nav1.9 currents elicited by 60 pulses at 1 Hz. CONCLUSION: These data suggest that AMI is a state-selective blocker of Nav1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines. PMID- 24228719 TI - Content and face validation of a curriculum for ultrasonic propulsion of calculi in a human renal model. AB - PURPOSE: Ultrasonic propulsion to reposition urinary tract calculi requires knowledge about ultrasound image capture, device manipulation, and interpretation. The purpose of this study was to validate a cognitive and technical skills curriculum to teach urologists ultrasonic propulsion to reposition kidney stones in tissue phantoms. MATERIALS AND METHODS: Ten board certified urologists recruited from a single institution underwent a didactic session on renal ultrasound imaging. Subjects completed technical skills modules in tissue phantoms, including kidney imaging, pushing a stone through a translucent maze, and repositioning a lower pole calyceal stone. Objective cognitive and technical performance metrics were recorded. Subjects completed a questionnaire to ascertain face and content validity on a five-point Likert scale. RESULTS: Eight urologists (80%) had never attended a previous ultrasound course, and nine (90%) performed renal ultrasounds less frequently than every 6 months. Mean cognitive skills scores improved from 55% to 91% (p<0.0001) on pre- and post-didactic tests. In the kidney phantom, 10 subjects (100%) repositioned the lower pole calyceal stone to at least the lower pole infundibulum, while 9 (90%) successfully repositioned the stone to the renal pelvis. A mean+/-SD (15.7+/-13.3) pushes were required to complete the task over an average of 4.6+/ 2.2 minutes. Urologists rated the curriculum's effectiveness and realism as a training tool at a mean score of 4.6/5.0 and 4.1/5.0, respectively. CONCLUSIONS: The curriculum for ultrasonic propulsion is effective and useful for training urologists with limited ultrasound proficiency in stone repositioning technique. Further studies in animate and human models will be required to assess predictive validity. PMID- 24228721 TI - Exchange coupling and its chemical trend studied by high-frequency EPR on heterometallic [Ln2Ni] complexes. AB - We applied high-frequency electron paramagnetic resonance to trinuclear 4f-3d heterometallic complexes, [{Ln(hfac)3}2{Ni(dpk)2(py)2}] (Ln = Y, Gd, Tb, and Ho; hfac = hexafluoroacetylacetonate, dpk = di-2-pyridyl ketoximate, and py = pyridine), and determined the exchange parameter J(Ln-Ni) as well as nickel(II) zero-field splitting parameters. In contrast to the antiferromagnetic Dy analogue, ferromagnetic couplings were precisely characterized as J(Gd-Ni)/kB = +0.301(4) K, J(Tb-Ni)/kB = +0.216(12) K, and J(Ho-Ni)/kB = +0.110(3) K (defined as -J(Ln-Ni)?J(Ln)(z)S(Ni)). PMID- 24228720 TI - Protein-C deficiency presenting as pulmonary embolism and myocardial infarction in the same patient. AB - Plasma protein-C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis occurring as a result of congenital protein-C deficiency is still controversial. We describe a young patient with heterozygous protein-C deficiency who experienced both pulmonary embolism as well as myocardial infarction due to thrombotic occlusion without underlying major risk factors. Acute myocardial infarction in young without underlying major risk factors may be evaluated for protein c deficiency. PMID- 24228722 TI - Global health: the importance of evidence-based medicine. AB - Global health is a varied field that comprises research, evaluation and policy that, by its definition, also occurs in disparate locations across the world. This forum article is introduced by our guest editor of the Medicine for Global Health article collection, Gretchen Birbeck. Here, experts based across different settings describe their personal experiences of global health, discussing how evidence-based medicine in resource-limited settings can be translated into improved health outcomes. PMID- 24228723 TI - Hospital to home: a geriatric educational program on effective discharge planning. AB - There has been increased attention on the needs of the burgeoning older adult population, with focus on the limited education and training experiences available in geriatric care. Older adults transitioning between levels of care often require increased attention, and the American Geriatrics Society (AGS) Task Force on the Future of Geriatric Medicine has encouraged greater training opportunities be provided to better understand the needs of this population. The Hospital to Home Program is one model of geriatric training emphasizing many of the AGS recommendations. Through qualitative analyses of 51 internal medicine residents' reflections, the authors report how this educational program is meeting the above need and share how Hospital to Home is enhancing residents' skills in creating a safe discharge for geriatric patients and their families. PMID- 24228724 TI - Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study. AB - BACKGROUND: Current International Diabetes Federation guidelines recommend a target HbA1c <7.0%, but many people with diabetes worldwide find this difficult to achieve, increasing their risk of developing complications. This publication examines the prevalence of diabetes complications and its association with baseline characteristics in people with type 2 diabetes who participated in the A1chieve study. METHODS: A1chieve was a 24-week, multinational, open-label, observational study of 66,726 people with type 2 diabetes who had begun using biphasic insulin aspart 30, insulin aspart, or insulin detemir in routine clinical care. Participants were enrolled from 28 countries across four continents (Asia, Africa, Europe and South America). Baseline measurements of disease characteristics included: glycated haemoglobin (HbA1c), fasting (FPG) and post-prandial plasma glucose (PPG), high- and low-density lipoprotein cholesterol (H- or LDL-C), systolic blood pressure (SBP), and body mass index (BMI). Data on complications and use of vascular disease preventative drugs were collected. RESULTS: Complication rates were high (27.2% had macrovascular complications and 53.5% had microvascular complications), particularly in Russia, and use of vascular disease preventative drugs was lower than expected. Age, BMI, diabetes duration, LDL-C, and SBP were positively associated, and HDL-C negatively associated, with macro- and microvascular complications (all p < 0.05). HbA1c and FPG were negatively associated with macrovascular complications (both p < 0.05), which may be linked to the cross-sectional study design. CONCLUSIONS: These results suggest a worldwide failure to achieve glycaemic targets. Better diabetes management with earlier initiation and optimisation of insulin regimens (e.g., with insulin analogues in the A1chieve population) may reduce the prevalence of vascular complications, improve the lives of people with diabetes and reduce the burden on healthcare systems. PMID- 24228725 TI - Evaluation of NGAL TestTM on Cobas 6000. AB - BACKGROUND: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). Our objectives were to evaluate the NGAL Test(TM) from Bioporto for both urine NGAL and plasma NGAL on the Cobas 6000 c501 (Roche Diagnostics, Rotkreuz, Switzerland) with matched measurements run on Hitachi 917, the method's linearity on the Cobas 6000 in urine, EDTA and Lithium Heparin (Li-Hep), the influence of using EDTA or Li-Hep tubes and, finally, the impact of freezing and thawing on the sample. METHODS: Forty matched samples of Li-Hep and EDTA plasma and 40 urine samples were analyzed for method, anticoagulant, and freeze-thaw comparisons. Linearity was assessed using high NGAL samples diluted in urine, EDTA, and Li-Hep plasma. Commercial internal controls were used for the imprecision study. RESULTS: The Cobas 6000 measured identically with the Hitachi 917, however, not in EDTA plasma (Median Difference = 17.50 MUg/L, p < 0.0001). Freeze-thaw process reduced NGAL ((EDTA: Mean Difference = = 15.13 MUg/L, p = 0.0014)(Li-Hep: Median Difference = = 6.5 MUg/L, p = 0.0129)). NGAL results were higher in Li-Hep plasma than in EDTA plasma ((Non thawed: Median Difference = = 14.5 MUg/L, p < 0.0001), (Thawed: Median Difference = = 21.5 MUg/L, p = 0.0003)). Linearity agreements were observed in all three specimens. Imprecision (CV%) was below 3%. CONCLUSION: The NGAL Test(TM) can be applied on the Cobas 6000 with acceptable performance, although the Cobas 6000 measured higher than the Hitachi 917 in EDTA plasma. Though clinically insignificant, we found that the freeze-thaw process had a reduced effect. NGAL results were higher in Li-Hep tubes than in EDTA tubes. Thus, for blood samples we recommend use of EDTA tubes for NGAL measurements. PMID- 24228726 TI - Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation. AB - BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disease with severe microcephaly at birth due to a pronounced reduction in brain volume and intellectual disability. Biallelic mutations in the WD repeat-containing protein 62 gene WDR62 are the genetic cause of MCPH2. However, the exact underlying pathomechanism of MCPH2 remains to be clarified. METHODS/RESULTS: We characterized the clinical, radiological, and cellular features that add to the human MCPH2 phenotype. Exome sequencing followed by Sanger sequencing in a German family with two affected daughters with primary microcephaly revealed in the index patient the compound heterozygous mutations c.1313G>A (p.R438H) / c.2864-2867delACAG (p.D955Afs*112) of WDR62, the second of which is novel. Radiological examination displayed small frontal lobes, corpus callosum hypoplasia, simplified hippocampal gyration, and cerebellar hypoplasia. We investigated the cellular phenotype in patient-derived lymphoblastoid cells and compared it with that of healthy female controls. WDR62 expression in the patient's immortalized lymphocytes was deranged, and mitotic spindle defects as well as abnormal centrosomal protein localization were apparent. CONCLUSION: We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2. PMID- 24228727 TI - Is the use of computer navigation in total knee arthroplasty improving implant positioning and function? A comparative study of 198 knees operated at a Norwegian district hospital. AB - BACKGROUND: There are few Scandinavian studies on the effect of computer assisted orthopedic surgery (CAOS) in total knee arthroplasty (TKA), compared to conventional technique (CON), and there is little information on effects in pain and function scores. This retrospective study has evaluated the effects of CAOS on radiological parameters and pain, function and quality of life after primary TKA. METHODS: 198 primary TKAs were operated by one surgeon in two district hospitals; 103 CAOS and 95 CON. The groups were evaluated based on 3 months post operative radiographs and a questionnaire containing the knee osteoarthritis outcome score (KOOS), the EQ-5D index score and a visual analogue scale (VAS) two years after surgery. Multiple linear regression method was used to investigate possible impact from exposure (CON or CAOS). RESULTS: On hip-knee-ankle radiographs, 20% of measurements were > +/-3 degrees of neutral in the CAOS group and 25% in the CON group (p = 0.37). For the femoral component, the number was 5% for CAOS and 18% for CON (p < 0.01). For the tibial component, the difference was not statistically significant (p = 0.58). In the sagittal plane, the surgeon tended to apply more femoral flexion and more posterior tibial slope with CAOS. We observed no statistically or clinically significant difference in KOOS score, VAS or ?EQ-5D (all p values >0.05), but there was a trend towards better scores for CAOS. Operation time was 3 minutes longer for CON (p = 0.37). CONCLUSIONS: CAOS can improve radiological measurements in primary TKA, and makes it possible to adjust component placement to the patient's anatomy. Over-all, the two methods are equal in pain, function and quality-of-life scores. PMID- 24228728 TI - Comparing implicit and synaesthetic number-space associations: Visuospatial and verbal spatial-numerical associations of response codes. AB - In the theory of the mental number line, number, and space are implicitly associated, giving rise to the spatial-numerical association of response codes (SNARC) effect, in which smaller numbers are more readily associated with the left side of space and larger numbers with the right, during a parity judgement task. Others, however, have argued that the SNARC effect is flexible and better explained by verbal rather than spatial associations. A few single-case studies on the SNARC effect have tested number-space synaesthetes, who make explicit associations between number and space. Here, we present data from experiments conducted on groups of synaesthetes and nonsynaesthetes on the classic SNARC parity judgement task with lateralized response keys and a modified version in which they responded to labels appearing on screen. Synaesthetes' behaviour was expected to differ from nonsynaesthetes' behaviour due to the explicit, fixed nature of their number-space associations, but both experiments show the two groups behaving in the same way, indicating that parity judgement tasks may not be tapping the same representation of number that gives rise to synaesthetic number-space experiences. PMID- 24228729 TI - Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease. AB - RATIONALE: Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to protein degradation. OBJECTIVES: To investigate whether autophagy is enhanced in locomotor muscles of stable patients with COPD, to quantify autophagy-related gene expression in these muscles, and to identify mechanisms of autophagy induction. METHODS: Muscle biopsies were obtained from two cohorts of control subjects and patients with COPD and the numbers of autophagosomes in the vastus lateralis and tibialis anterior muscles, the levels of LC3B protein lipidation, and the expression of autophagy-related genes were measured in the vastus lateralis muscle. To investigate potential pathways that might induce the activation of autophagy, measures were taken of protein kinase B (AKT), mTORC1, and AMPK pathway activation, transcription factor regulation, proteasome activation, and oxidative stress. MEASUREMENTS AND MAIN RESULTS: Autophagy is enhanced in the locomotor muscles of patients with COPD as shown by significantly higher numbers of autophagosomes in affected muscles as compared with control subjects. Autophagosome number inversely correlates with FEV1. In the vastus lateralis, LC3B protein lipidation is increased by COPD and the expression of autophagy-related gene expressions is up-regulated. LC3B lipidation inversely correlates with thigh cross-sectional area, FEV1, and FEV1/FVC ratio. Enhanced autophagy is associated with activation of the AMPK pathway and FOXO transcription factors, inhibition of the mTORC1 and AKT pathways, and the development of oxidative stress. CONCLUSIONS: Autophagy is significantly enhanced in locomotor muscles of stable patients with COPD. The degree of autophagy correlates with severity of muscle atrophy and lung function impairment. PMID- 24228730 TI - Biochemical screening for aneuploidy in patients with donor oocyte pregnancies compared with autologous pregnancies. AB - OBJECTIVE: The objective was to determine if the rate of abnormal biochemical markers is different in pregnancies conceived by donor oocyte versus those conceived by autologous oocytes. METHODS: This is a retrospective cohort study of patients who underwent risk assessment for aneuploidy. Pregnancies conceived by egg donation were matched with control groups who conceived using their own eggs. The primary outcomes were incidence of low PAPP-A or free bHCG in the first trimester or elevated MSAFP, free bHCG or Inhibin A, or low uE3 in the second trimester. RESULTS: 260 singleton gestations were identified who conceived via oocyte donor. There was a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (8% versus 2%, p = 0.028) compared to a control group matched by maternal age. There was also a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (7% versus 2%, p = 0.01) compared to a control group matched by age of the egg donor. CONCLUSION: Pregnancies conceived by egg donation are more likely to have an unexplained elevation in MSAFP compared to pregnancies not conceived by egg donation regardless of age. Egg donation itself is not associated with other biochemical abnormalities. PMID- 24228731 TI - Retraction: The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells. PMID- 24228732 TI - Beyond Darwin: evolvability and the generation of novelty. PMID- 24228733 TI - Snapshots of Dirac fermions near the Dirac point in topological insulators. AB - The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices. PMID- 24228734 TI - The Drosophila early ovarian transcriptome provides insight to the molecular causes of recombination rate variation across genomes. AB - BACKGROUND: Evidence in yeast indicates that gene expression is correlated with recombination activity and double-strand break (DSB) formation in some hotspots. Studies of nucleosome occupancy in yeast and mice also suggest that open chromatin influences the formation of DSBs. In Drosophila melanogaster, high resolution recombination maps show an excess of DSBs within annotated transcripts relative to intergenic sequences. The impact of active transcription on recombination landscapes, however, remains unexplored in a multicellular organism. We then investigated the transcription profile during early meiosis in D. melanogaster females to obtain a glimpse at the relevant transcriptional dynamics during DSB formation, and test the specific hypothesis that DSBs preferentially target transcriptionally active genomic regions. RESULTS: Our study of transcript profiles of early- and late-meiosis using mRNA-seq revealed, 1) significant differences in gene expression, 2) new genes and exons, 3) parent of-origin effects on transcription in early-meiosis stages, and 4) a nonrandom genomic distribution of transcribed genes. Importantly, genomic regions that are more actively transcribed during early meiosis show higher rates of recombination, and we ruled out DSB preference for genic regions that are not transcribed. CONCLUSIONS: Our results provide evidence in a multicellular organism that transcription during the initial phases of meiosis increases the likelihood of DSB and give insight into the molecular determinants of recombination rate variation across the D. melanogaster genome. We propose that a model where variation in gene expression plays a role altering the recombination landscape across the genome could provide a molecular, heritable and plastic mechanism to observed patterns of recombination variation, from the high level of intra-specific variation to the known influence of environmental factors and stress conditions. PMID- 24228735 TI - Bacterial proteasome and PafA, the pup ligase, interact to form a modular protein tagging and degradation machine. AB - Proteasome-containing bacteria possess a tagging system that directs proteins to proteasomal degradation by conjugating them to a prokaryotic ubiquitin-like protein (Pup). A single ligating enzyme, PafA, is responsible for Pup conjugation to lysine side chains of protein substrates. As Pup is recognized by the regulatory subunit of the proteasome, Pup functions as a degradation tag. Pup presents overlapping regions for binding of the proteasome and PafA. It was, therefore, unclear whether Pup binding by the proteasome regulatory subunit, Mpa, and by PafA are mutually exclusive events. The work presented here provides evidence for the simultaneous interaction of Pup with both Mpa and PafA. Surprisingly, we found that PafA and Mpa can form a complex both in vitro and in vivo. Our results thus suggest that PafA and the proteasome can function as a modular machine for the tagging and degradation of cytoplasmic proteins. PMID- 24228736 TI - Self-assembly properties of semiconducting donor-acceptor-donor bithienyl derivatives of tetrazine and thiadiazole-effect of the electron accepting central ring. AB - Scanning tunneling microscopy was used to study the effect of the electron accepting unit and the alkyl substituent's position on the type and extent of 2D supramolecular organization of penta-ring donor-acceptor-donor (DAD) semiconductors, consisting of either tetrazine or thiadiazole central acceptor ring symmetrically attached to two bithienyl groups. Microscopic observations of monomolecular layers on HOPG of four alkyl derivatives of the studied adsorbates indicate significant differences in their 2D organizations. Ordered monolayers of thiadiazole derivatives are relatively loose and, independent of the position of alkyl substituents, characterized by large intermolecular separation of acceptor units in the adjacent molecules located in the face-to-face configuration. The 2D supramolecular architecture in both derivatives of thiadiazole is very sensitive to the alkyl substituent's position. Significantly different behavior is observed for derivatives of tetrazine (which is a stronger electron acceptor). Stronger intermolecular DA interactions in these adsorbates generate an intermolecular shift in the monolayer, which is a dominant factor determining the 2D structural organization. As a consequence of this molecular arrangement, tetrazine groups (A segments) face thiophene rings (D segments) of the neighboring molecules. Monolayers of tetrazine derivatives are therefore much more densely packed and characterized by similar pi-stacking of molecules independently of the position of alkyl substituents. Moreover, a comparative study of 3D supramolecular organization, deduced from the X-ray diffraction patterns, is also presented clearly confirming the polymorphism of the studied adsorbates. PMID- 24228738 TI - Can RENAL and PADUA nephrometry indices predict complications of laparoscopic cryoablation for clinical stage T1 renal tumors? AB - OBJECTIVE: Assessment of anatomical complexity with the RENAL (radius; exophytic/endophytic; nearness; anterior/posterior; location) and preoperative aspects and dimensions used for anatomical classification (PADUA) nephrometry indices is used to predict complications related to surgical extirpation treatment for patients with clinical T1a/b renal mass. This single center study aims to investigate the value of these indices to predict complications in a cohort of patients treated with laparoscopic cryoablation (LCA) for cT1 renal mass. MATERIALS AND METHODS: Single institution data from consecutive LCA procedures were prospectively collected from December 2006 to April 2013. Renal mass anatomical complexity was categorized according to RENAL and PADUA indices. Comorbidity was assessed by the Charlson-index. Intraoperative complications (IOCs) were reviewed and categorized: blood loss >100 mL, conversion, tumor fracture, and incomplete ablation. Postoperative complications (POCs) were graded using the modified Clavien-index. Univariate and multivariate logistic regression models addressed the risk for complications. RESULTS: Ninety-nine LCA procedures were included. The median RENAL-score was 7.0 (standard deviation [SD] 1.7), and the median PADUA-score was 8.0 (SD 1.6). IOC occurred in 19 procedures (19%). The risk for IOC was significantly correlated (p<0.05) with tumor diameter (mm), surface, volume, the RENAL domains "R-size," "N-nearness to collecting system," "RENAL score," and the PADUA domain "diameter." In multivariate analysis with surgical complication as the independent variable, tumor diameter, surface, and volume were determining factors. A threshold was set for 35 mm tumor diameter, it being predictive for an increased risk for IOC performing LCA. Twenty-three POC occurred in 20 patients. On univariate analysis, the RENAL domain "nearness to collecting system," and no PADUA domains, had a significant association with POC. CONCLUSION: The RENAL score, and not the PADUA score, is associated with a higher risk for IOC. A noncategorized method of scoring tumor diameter showed a more significant correlation with the risk for IOC than the categorized method of the nephrometry indices. As a result a threshold diameter of 35 mm was established. PMID- 24228737 TI - N-type voltage gated calcium channels mediate excitatory synaptic transmission in the anterior cingulate cortex of adult mice. AB - Voltage gated calcium channels (VGCCs) are well known for its importance in synaptic transmission in the peripheral and central nervous system. However, the role of different VGCCs in the anterior cingulate cortex (ACC) has not been studied. Here, we use a multi-electrode array recording system (MED64) to study the contribution of different types of calcium channels in glutamatergic excitatory synaptic transmission in the ACC. We found that only the N-type calcium channel blocker omega-conotoxin-GVIA (omega-Ctx-GVIA) produced a great inhibition of basal synaptic transmission, especially in the superficial layer. Other calcium channel blockers that act on L-, P/Q-, R-, and T-type had no effect. We also tested the effects of several neuromodulators with or without omega-Ctx-GVIA. We found that N-type VGCC contributed partially to (1S,3R)-1 aminocyclopentane-1,3-dicarboxylic acid- and (R)-Baclofen-induced synaptic inhibition. By contrast, the inhibitory effects of 2-Chloroadenosine and carbamoylcholine chloride did not differ with or without omega-Ctx-GVIA, indicating that they may act through other mechanisms. Our results provide strong evidence that N-type VGCCs mediate fast synaptic transmission in the ACC. PMID- 24228739 TI - Divergent differentiation of skeletal progenitors into cartilage and tendon: lessons from the embryonic limb. AB - Repairing damaged cartilage and tendons is a major challenge of regenerative medicine. There has been great progress in the past decade toward obtaining stem cells for regenerative purposes from a variety of sources. However, the development of procedures to direct and maintain the differentiation of progenitors into cartilage or tendon is still a hurdle to overcome in regenerative medicine of the musculoskeletal system. This is because connective tissues often lack stable phenotypes and retain plasticity to return to the initial stages of differentiation or to transdifferentiate into another connective tissue cell lineage. This makes it necessary to unravel the molecular basis that is responsible for the differentiation of connective tissue cell lineages. In this review, we summarize the investigations performed in the past two decades to unravel the signals that regulate the differentiation of skeletal cell progenitors into cartilage and tendons during embryonic limb development. The data obtained in those studies demonstrate that Tgfbeta, BMP, FGF, and Wnt establish a complex signaling network that directs the differentiation of skeletal cell progenitors. Remarkably, in the embryonic digit model, the divergent differentiation of progenitors depends on the temporal coordination of those signals, rather than being specified by an individual signaling pathway. Due to its potential medical relevance, we highlight the importance of the coordinate influence of the Tgfbeta and BMP pathways in the differentiation of cell progenitors into tendon or cartilage. PMID- 24228740 TI - Isolated pancreatic heamorrhage in association with anticoagulation. AB - Haemorrhage is the primary complication of anticoagulation therapy with the gastrointestinal, urinary and nasal tracts the most common sites of bleeding. Haematoma within solid organs is uncommon especially in the absence of blunt trauma. We describe two patients on long term Warfarin therapy who developed focal haematomas within the pancreas. To the best of our knowledge these are the first isolated unprovoked focal pancreatic hematoma cases reported in the literature. The non-specific clinical symptoms and confusing radiological features mimicked pancreatic malignancy and this led to misdiagnosis in the one patient who underwent unnecessary surgical exploration. The haematoma was correctly identified in the second patient who was managed conservatively and had an uneventful recovery. PMID- 24228741 TI - The electrode as organolithium reagent: catalyst-free covalent attachment of electrochemically active species to an azide-terminated glassy carbon electrode surface. AB - The reaction of a lithium acetylide-ethylenediamine complex with azide-terminated glassy carbon surfaces affords 1,2,3-triazolyllithium surface groups that are active toward covalent C-C coupling reactions, including salt metathesis with an aliphatic halide and nucleophilic addition at an aldehyde. Surface ferrocenyl groups were introduced by reaction with (6-iodohexyl)ferrocene; the voltammetry of electrode samples shows narrow, symmetric peaks indicating uniform attachment. X-ray photoelectron and reflectance infrared spectroscopic data provide further support for the surface-attached products. Formation of the 1,2,3 triazolyllithium linkage requires neither a catalyst nor a strained alkyne. Coverages obtained by this route are similar to those obtained by the more common Cu(I)-catalyzed alkyne-azide coupling (CuAAC) of ethynylferrocene with surface azides. Preconditioning of the glassy carbon disk electrodes at ambient temperature under nitrogen affords coverages comparable to those reported with preconditioning at 1000 degrees C under hydrogen/nitrogen. PMID- 24228742 TI - Millennium Development Goals 4 and 5: progress and challenges. AB - The Millennium Development Goals have galvanized efforts to improve child survival (MDG-4) and maternal health (MDG-5). There has been important progress on both MDGs at global level, although it now appears that few countries will reach them by the target date of 2015. There are known and efficacious interventions to address most of the major causes of these deaths, but important gaps remain. The biggest challenge is to ensure that all women and children have access to life-saving interventions. Current levels of intervention coverage are too low, representing missed opportunities. Providing services at the community level is an important emerging priority, but preventing maternal and neonatal deaths also requires access to health facilities. Readers of the Medicine for Global Health collection in BMC Medicine are urged to make maternal and child health one of their key concerns, even if they work on other topics. PMID- 24228743 TI - Comparative efficacy of glimepiride and metformin in monotherapy of type 2 diabetes mellitus: meta-analysis of randomized controlled trials. AB - BACKGROUND: Metformin treatment has been the most recommended monotherapy of type 2 diabetes mellitus (T2DM) for decades but is challenged by new antidiabetic drugs. This study conducted a meta-analysis of randomized controlled trials (RCT) comparing the efficacy of metformin and glimepiride in monotherapy of T2DM. METHODS: A literature search for RCTs on glimepiride and metformin was conducted on the bibliographic databases, including PubMed, Cochrane Library and ScienceDirect, from their inceptions to 25 Mar 2013. All RCTs were selected according to pre-specified eligibility criteria. The quality of articles was assessed with the Cochrane's risk of bias tool. Statistical meta-analysis evaluated the overall effects and biochemical indices of T2DM. Sensitivity and subgroup analyses evaluated the robustness and explained the heterogeneity of the results. Begg and Egger's tests quantified possible publication biases. Results were represented as "standard mean difference or odds ratio [95% confidence internals] P value". RESULTS: Fifteen RCTs with 1681 adult T2DM patients were included for meta-analysis. Metformin was not better than glimepiride in overall efficacy in controlling the levels of HbA1c, postprandial blood sugar (PPBS), fasting plasma insulin (FINS), systolic and diastolic blood pressures (SBP and DBP), and high density lipoprotein (HDL). Metformin was only more effective than glimepiride in controlling the levels of total cholesterol (TC, 0.33 [0.03, 0.63], P = 0.03), low-density lipoprotein (LDL, 0.35 [0.16, 0.53], P = 0.0002) and triglycerides (TG, 0.26 [0.05, 0.46], P = 0.01). Odds ratios of adverse events showed that glimepiride was more likely to induce hypoglycemia episodes and metformin was with a higher risk of gastrointestinal upset. CONCLUSION: Metformin was not significantly better than glimepiride in glycemic control of T2DM, suggesting that glimepiride would be a good choice second to metformin in the monotherapy of T2DM. PMID- 24228744 TI - Formative evaluation of a multi-component, education-based intervention to improve processes of end-of-life care. AB - A multicomponent, palliative care, education-based intervention was implemented in six Veterans Affairs Medical Centers in the southeast United States. The intervention comprised onsite staff training plus supporting written materials, installation of an electronic order set, and follow-up consultations. Training included large-group didactic presentations, small-group clinical demonstrations, and one-on-one consultations. The intervention strategy was targeted broadly to hundreds of hospital providers, including physician, nursing, and ancillary staff. The purpose was to train staff in identifying actively dying patients and implementing best practices of home-based hospice care. A formative evaluation was conducted utilizing semistructured telephone interviews with key informants from each site. Qualitative data analysis revealed processes that facilitated or impeded uptake of the intervention. Results will be used to inform ongoing and future clinical initiatives and optimize future implementation of education-based interventions to improve adoption of best practices for end-of-life care within acute care settings. PMID- 24228745 TI - Schoolgirls and soccer moms: a content analysis of free "teen" and "MILF" online pornography. AB - Viewing free online pornographic videos has increasingly become a common behavior among young people, although little is known about the content of these videos. The current study analyzed the content of two popular female-age-based types of free, online pornography (teen and MILF) and examined nuances in the portrayal of gender and access to power in relation to the age of the female actor. A total of 100 videos were selected from 10 popular Web sites, and their content was coded using independent raters. Vaginal intercourse and fellatio were the most frequently depicted sexual acts. The use of sex toys, paraphilias, cuddling, and condom use were rare, as were depictions of coercion. Control of the pace and direction of sexual activity was typically shared by the male and female actors. Moreover, there were no gender differences in initiation of sexual activity, use of persuasion, portrayals of sexual experience, or in professional status. However, female actors in MILF videos were portrayed as more agentic and were more likely to initiate sexual activity, control the pace of sexual activity, and have a higher professional status. Implications regarding the role of pornography in generating or reinforcing sexual norms or scripts are discussed. PMID- 24228746 TI - Lower concentrations of phthalates induce proliferation in human breast cancer cells. AB - OBJECTIVE: To explore the effect and pathway of phthalates on the growth of MCF-7 breast cancer cells. METHODS: MCF-7 cells were treated with benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP) (10(-10)-10(-4) mol/l). After incubation for 24, 48, 72, and 92 h, the cells were harvested and extracted for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proteins involving proliferative and apoptotic pathways were evaluated by Western blot analysis. RESULTS: MTT assay revealed cell toxicity at more than 10(-5) mol/l for DEHP and at 10(-4) mol/l for both BBP and DBP in MCF-7 cells. Cell proliferation was significantly increased at 10(-8)-10( 5) mol/l of BBP and DBP, and at 10(-8)-10(-6) mol/l of DEHP treatment. Proliferating cell nuclear antigen (PCNA) was substantially increased in cultures with DEHP (10(-8)-10(-6) mol/l), BBP (10(-8)-10(-5) mol/l), and DBP (10(-7)-10( 5) mol/l). Obvious increases in PI3K, p-AKT, and PCNA were noted in cultures with 17beta-estradiol, BBP, DBP, and DEHP. Estrogen receptor alpha expression was also notably increased in treatment with estradiol, BBP, DBP, and DEHP. CONCLUSIONS: The present study demonstrates that, even at a very low concentration, BBP, DBP, and DEHP were not only still capable of inducing a proliferative effect through the PI3K/AKT signaling pathway but also displaying estrogenic activity. Therefore, the current reference doses for phthalates defined by governments should be further evaluated. PMID- 24228747 TI - The spinal stenosis pedometer and nutrition lifestyle intervention (SSPANLI) randomized controlled trial protocol. AB - BACKGROUND: Because of symptoms, people with lumbar spinal stenosis (LSS) are often inactive, and this sedentary behaviour implies risk for diseases including obesity. Research has identified body mass index as the most powerful predictor of function in LSS. This suggests that function may be improved by targeting weight as a modifiable factor. An e-health lifestyle intervention was developed aimed at reducing fat mass and increasing physical activity in people with LSS. The main components of this intervention include pedometer-based physical activity promotion and nutrition education. METHODS/DESIGN: The Spinal Stenosis Pedometer and Nutrition Lifestyle INTERVENTION (SSPANLI) was developed and piloted with 10 individuals. The protocol for a randomized controlled trail comparing the SSPANLI intervention to usual non-surgical care follows. One hundred six (106) overweight or obese individuals with LSS will be recruited. Baseline and follow-up testing includes dual energy x-ray absorptiometry, blood draw, 3-day food record, 7-day accelerometry, questionnaire, maximal oxygen consumption, neurological exam, balance testing and a Self-Paced Walking Test. INTERVENTION: During Week 1, the intervention group will receive a pedometer, and a personalized consultation with both a Dietitian and an exercise specialist. For 12 weeks participants will log on to the e-health website to access personal step goals, walking maps, nutrition videos, and motivational quotes. Participants will also have access to in-person Coffee Talk meetings every 3 weeks, and meet with the Dietitian and exercise specialist at week 6. The control group will proceed with usual care for the 12-week period. Follow-up testing will occur at Weeks 13 and 24. DISCUSSION: This lifestyle intervention has the potential to provide a unique, non-surgical management option for people with LSS. Through decreased fat mass and increased function, we may reduce risk for obesity, chronic diseases of inactivity, and pain. The use of e-health interventions provides an opportunity for patients to become more involved in managing their own health. Behaviour changes including increased physical activity, and improved dietary habits promote overall health and quality of life, and may decrease future health care needs in this population. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01902979. PMID- 24228749 TI - Consensus Review and Definition of Nonallergic Rhinitis With a Focus on Vasomotor Rhinitis, Proposed to Be Known henceforth as Nonallergic Rhinopathy: Introduction to Part 2. AB - "Nonallergic vasomotor rhinitis" (also referred to as nonallergic rhinitis and/or idiopathic rhinitis) is a term that has been used to describe a common nasal condition of unclear pathophysiology. Clinical options for patients are limited by a lack of straight-forward diagnostic criteria and poorly defined and heterogeneous populations in clinical trials. A roundtable conference convened in December 2008 addressed these challenges. Part 1 of the proceedings of that meeting provided a consensus definition of "nonallergic rhinopathy," proposed to replace the former terms above based on the clinical characteristics of the disease, which were described in individual papers. Part 2 of the proceedings uses the revised definition for a consensus discussion on appropriate criteria for enrolling subjects in future clinical studies of the efficacy of potential treatments for this disease. PMID- 24228748 TI - Acupuncture for infantile colic: a blinding-validated, randomized controlled multicentre trial in general practice. AB - OBJECTIVE: Infantile colic is a painful condition in the first months of infancy. Acupuncture is used in Scandinavia as a treatment for infantile colic. A randomized controlled trial was carried out with the aim of testing the hypothesis that acupuncture treatment has a clinically relevant effect for this condition. DESIGN: A prospective, blinding-validated, randomized controlled multicentre trial in general practice. Research assistants and parents were blinded. SETTING: 13 GPs' offices in Southern Norway. INTERVENTION: Three days of bilateral needling of the acupuncture point ST36, with no treatment as control. SUBJECTS: 113 patients were recruited; 23 patients were excluded, and 90 randomized; 79 diaries and 84 interviews were analysed. MAIN OUTCOME MEASURES: Difference in changes in crying time during the trial period between the intervention and control group. RESULTS: The blinding validation questions showed a random distribution with p = 0.41 and 0.60, indicating true blinding. We found no statistically significant difference in crying time reduction between acupuncture and control group at any of the measured intervals, nor in the main analysis of differences in changes over time (p = 0.26). There was a tendency in favour of the acupuncture group, with a non-significant total baseline-corrected mean of 13 minutes (95% CI -24 to + 51) difference in crying time between the groups. This was not considered clinically relevant, according to protocol. CONCLUSION: This trial of acupuncture treatment for infantile colic showed no statistically significant or clinically relevant effect. With the current evidence, the authors suggest that acupuncture for infantile colic should be restricted to clinical trials. PMID- 24228750 TI - Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. AB - Surface coatings of nanoparticles (NPs) are known to influence advantageous features of NPs as well as potential toxicity. Iron oxide (Fe3O4) NPs are applied for both medical diagnostics and targeted drug delivery. We investigated the potential cytotoxicity and genotoxicity of uncoated iron oxide (U-Fe3O4) NPs in comparison with oleate-coated iron oxide (OC-Fe3O4) NPs. Testing was performed in vitro in human lymphoblastoid TK6 cells and in primary human blood cells. For cytotoxicity testing, relative growth activity, trypan blue exclusion, (3)H thymidine incorporation and cytokinesis-block proliferation index were assessed. Genotoxicity was evaluated by the alkaline comet assay for detection of strand breaks and oxidized purines. Particle characterization was performed in the culture medium. Cellular uptake, morphology and pathology were evaluated by electron microscopy. U-Fe3O4 NPs were found not to be cytotoxic (considering interference of NPs with proliferation test) or genotoxic under our experimental conditions. In contrast, OC-Fe3O4 NPs were cytotoxic in a dose-dependent manner, and also induced DNA damage, indicating genotoxic potential. Intrinsic properties of sodium oleate were excluded as a cause of the toxic effect. Electron microscopy data were consistent with the cytotoxicity results. Coating clearly changed the behaviour and cellular uptake of the NPs, inducing pathological morphological changes in the cells. PMID- 24228751 TI - AA amyloidosis-resistant CE/J mice have Saa1 and Saa2 genes that encode an identical SAA isoform. AB - The CE/J mouse strain is resistant to amyloid A protein (AA) amyloidosis. In contrast to AA amyloidosis-susceptible mouse strains that concomitantly express serum amyloid A precursor protein (SAA) types 1 and 2 isoforms encoded by the Saa1 and Saa2 genes, respectively, in response to inflammatory stimulation from the liver, CE/J mice express only a single SAA isoform named SAA2.2. In addition, CE/J mice uniquely possess a Q30L amino acid substitution in SAA2.2 that inhibits amyloidogenesis. To elucidate the genetic basis underlying the expression of only a single SAA isoform in this strain, we conducted PCR cloning and nucleotide sequencing of the Saa1 and Saa2 genes from the CE/J genome. We revealed that CE/J mice possess functional Saa1 and Saa2 genes. Intriguingly, the two genes were identical with respect to amino acid sequence, each encoding the SAA2.2 isoform. RT-PCR analysis of inflamed liver tissue from CE/J mice demonstrated that both genes are expressed at equivalent levels. Reporter assays revealed that promoter/enhancer sequences of Saa1 and Saa2 genes in CE/J are also functional. These results indicate that the SAA2.2 isoform in CE/J is a mixture of Saa1 and Saa2 gene products. PMID- 24228752 TI - Can contraction patterns predict neonatal outcomes? AB - OBJECTIVE: To estimate the association between contraction patterns in labor and neonatal outcomes. METHODS: A nested case-control study within a consecutive term birth cohort included women in labor with intrauterine pressure catheters (IUPCs) who reached the second stage. Cases were women delivering neonates with composite morbidity: special care or intensive care unit admission, umbilical artery pH <= 7.1 or 5-min Apgar < 7. The control group delivered without any components of the composite morbidity. Contraction frequency, duration, relaxation time, Montevideo units (MVUs) and baseline tone in the last 30 min prior to delivery were compared. We used logistic regression to adjust for potential confounders and receiver operating characteristic curves to evaluate the ability of contraction parameters to predict adverse neonatal outcomes. RESULTS: There were 183 cases of adverse neonatal outcomes and 2172 controls without the composite outcome. Contraction duration, relaxation time, MVUs and baseline tone did not significantly differ between the groups. Tachysystole was more common in women with the adverse neonatal outcome (21% versus 15%, p = 0.01). A model including tachysystole, oxytocin use and nulliparity did not adequately predict the adverse outcome (AUC = 0.61). CONCLUSIONS: Although tachysystole is associated with adverse neonatal outcomes, uterine activity cannot be used to predict neonatal outcome. PMID- 24228753 TI - Purification and characterization of plantaricin 163, a novel bacteriocin produced by Lactobacillus plantarum 163 isolated from traditional Chinese fermented vegetables. AB - Presumptive lactic acid bacteria (LAB) strains isolated from traditional Chinese fermented vegetables were screened for bacteriocin production. A novel bacteriocin-producing strain, Lactobacillus plantarum 163, was identified on the basis of its physiobiochemical characteristics and characterized by 16S rDNA sequencing. The novel bacteriocin, plantaricin 163, produced by Lb. plantarum 163 was purified by salt precipitation, gel filtration, and reverse-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of plantaricin 163 revealed the molecular weight to be 3553.2 Da. The complete amino acid sequence showed VFHAYSARGNYYGNCPANWPSCRNNYKSAGGK, and no similarity to known bacteriocins was found. Plantaricin 163 was highly thermostable (20 min, 121 degrees C), active in the presence of acidic pH (3-5), sensitive to protease, and exhibited broad-spectrum antimicrobial activity against LAB and other tested Gram positive and Gram-negative bacteria. The results suggest that plantaricin 163 may be employed as a biopreservative in the food industry. PMID- 24228755 TI - Open questions: Zombie projects, translational research, and the real secret of the inside of the cell. PMID- 24228754 TI - Silver-catalyzed vinylogous fluorination of vinyl diazoacetates. AB - A silver-catalyzed vinylogous fluorination of vinyl diazoacetates to generate gamma-fluoro-alpha,beta-unsaturated carbonyls is presented. Application of this method to the fluorination of farnesol and steroid derivatives was achieved. PMID- 24228756 TI - Large, negative magnetoresistance in an oleic acid-coated Fe(3)O(4) nanocrystal self-assembled film. AB - An oleic acid-coated Fe3O4 nanocrystal self-assembled film was fabricated via drop casting of colloidal particles on a SiO2/Si substrate. The film exhibited bifurcation of the zero-field-cooled and field-cooled magnetizations around 250 K. The nonlinear current-voltage (I-V) characteristics between the source and drain electrodes in both zero and non-zero magnetic fields (H) were observed above and below the bifurcation temperature. A large negative magnetoresistance (MR ~ -60%) was achieved at 200 K and H = 1 T. Even at 295 K and 0.2 T, the negative MR (~ -50%) persisted. A Fowler-Nordheim plot and power-law scaling of the I-V characteristics revealed that the current flows through two-dimensional (2D) percolated electron tunneling paths. The enlargement of MR can be attributed to spin-dependent electron tunneling between magnetically coupled Fe3O4 nanocrystals self-assembled in 2D ordered arrays. PMID- 24228758 TI - Ordering of poly(3-hexylthiophene) in solution and on substrates induced by concentrated sulfuric acid. AB - The ordering of poly(3-hexylthiophene) (P3HT) molecules in dilute P3HT/chloroform solutions was accelerated by adding small amounts of concentrated H2SO4. The concentrated H2SO4 stimulates the nucleation of crystals, which controls the overall rate of P3HT crystallization. Dispersed nuclei spur P3HT solution crystallization, and adsorbed nuclei induce P3HT crystallization on substrates. By AFM, the morphology of P3HT nanowhiskers prepared in solution differ from those prepared on substrates, and nanowhisker structure and growth kinetics was further investigated using Raman spectroscopy and UV-vis adsorption spectroscopy. All P3HT nanowhiskers are well-ordered. PMID- 24228759 TI - Structure of signal peptide peptidase A with C-termini bound in the active sites: insights into specificity, self-processing, and regulation. AB - Bacterial signal peptide peptidase A (SppA) is a membrane-bound enzyme that utilizes a serine/lysine catalytic dyad mechanism to cleave remnant signal peptides within the cellular membrane. Bacillus subtilis SppA (SppABS) oligomerizes into a homo-octameric dome-shaped complex with eight active sites, located at the interface between each protomer. In this study, we show that SppABS self-processes its own C-termini. We have determined the crystal structure of a proteolytically stable fragment of SppABSK199A that has its C-terminal peptide bound in each of the eight active sites, creating a perfect circle of peptides. Substrate specificity pockets S1, S3, and S2' are identified and accommodate C-terminal residues Tyr331, Met329, and Tyr333, respectively. Tyr331 at the P1 position is conserved among most Bacillus species. The structure reveals that the C-terminus binds within the substrate-binding grooves in an antiparallel beta-sheet fashion. We show, by C-terminal truncations, that the C terminus is not essential for oligomeric assembly. Kinetic analysis shows that a synthetic peptide corresponding to the C-terminus of SppABS competes with a fluorometric peptide substrate for the SppABS active site. A model is proposed for how the C-termini of SppA may function in the regulation of this membrane bound self-compartmentalized protease. PMID- 24228757 TI - Designing anti-inflammatory drugs from parasitic worms: a synthetic small molecule analogue of the Acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis. AB - In spite of increasing evidence that parasitic worms may protect humans from developing allergic and autoimmune diseases and the continuing identification of defined helminth-derived immunomodulatory molecules, to date no new anti inflammatory drugs have been developed from these organisms. We have approached this matter in a novel manner by synthesizing a library of drug-like small molecules based upon phosphorylcholine, the active moiety of the anti inflammatory Acanthocheilonema viteae product, ES-62, which as an immunogenic protein is unsuitable for use as a drug. Following preliminary in vitro screening for inhibitory effects on relevant macrophage cytokine responses, a sulfone containing phosphorylcholine analogue (11a) was selected for testing in an in vivo model of inflammation, collagen-induced arthritis (CIA). Testing revealed that 11a was as effective as ES-62 in protecting DBA/1 mice from developing CIA and mirrored its mechanism of action in downregulating the TLR/IL-1R transducer, MyD88. 11a is thus a novel prototype for anti-inflammatory drug development. PMID- 24228760 TI - Cognitive performance in older elderly men with late-life depression and cardiovascular comorbidities: symptomatological correlation. AB - BACKGROUND: Whether depression or cardiovascular disease would have a greater effect on worsening cognitive impairment in the burgeoning older elderly population is uncertain. Which disorder causes greater cognitive impairment was investigated. METHODS: A cross section of 207 cognitively impaired older elderly (>=75 years old) men was recruited from outpatient clinics in southern Taiwan between 2004 and 2008. Their medical charts were reviewed for their history of medical illnesses, and those undergoing a current major depressive episode were screened using the Mini-International Neuropsychiatric Interview. Four groups of men were enrolled: 33 healthy controls (HC), 101 cognitively impaired patients with cardiovascular comorbidities (CVCs), 34 patients with late-life depression (LLD), and 49 patients with LLD and cardiovascular comorbidities (LLD + CVC). Several neuropsychological tests (e.g., Mini-Mental State Examination (MMSE), WCST, and Trail Making Test (TMT) parts A and B) were used to assess the participants. RESULTS: Cognitive function scores were highest in the HC group and lowest in the LLD + CVC group. There were no significant differences between the two groups with LLD comorbidity, and LLD was mostly associated with cognitive performance. LLD + CVC group members had the lowest recall memory, but their overall MMSE score was not significantly different. Moreover, this group had a higher but nonsignificantly different perseverative error than did the LLD group. Similarly, the LLD + CVC group was nonsignificantly slower at the TMT-A and TMT-B tasks than was the LLD group. CONCLUSIONS: LLD worsens neuropsychological function more than cardiovascular comorbidities do. PMID- 24228761 TI - STaRRRT: a table of short tandem repeats in regulatory regions of the human genome. AB - BACKGROUND: Tandem repeats (TRs) are unstable regions commonly found within genomes that have consequences for evolution and disease. In humans, polymorphic TRs are known to cause neurodegenerative and neuromuscular disorders as well as being associated with complex diseases such as diabetes and cancer. If present in upstream regulatory regions, TRs can modify chromatin structure and affect transcription; resulting in altered gene expression and protein abundance. The most common TRs are short tandem repeats (STRs), or microsatellites. Promoter located STRs are considerably more polymorphic than coding region STRs. As such, they may be a common driver of phenotypic variation. To study STRs located in regulatory regions, we have performed genome-wide analysis to identify all STRs present in a region that is 2 kilobases upstream and 1 kilobase downstream of the transcription start sites of genes. RESULTS: The Short Tandem Repeats in Regulatory Regions Table, STaRRRT, contains the results of the genome-wide analysis, outlining the characteristics of 5,264 STRs present in the upstream regulatory region of 4,441 human genes. Gene set enrichment analysis has revealed significant enrichment for STRs in cellular, transcriptional and neurological system gene promoters and genes important in ion and calcium homeostasis. The set of enriched terms has broad similarity to that seen in coding regions, suggesting that regulatory region STRs are subject to similar evolutionary pressures as STRs in coding regions and may, like coding region STRs, have an important role in controlling gene expression. CONCLUSIONS: STaRRRT is a readily-searchable resource for investigating potentially polymorphic STRs that could influence the expression of any gene of interest. The processes and genes enriched for regulatory region STRs provide potential novel targets for diagnosing and treating disease, and support a role for these STRs in the evolution of the human genome. PMID- 24228766 TI - Synthesis of (TDAE)(O2SSO2)(s) and discovery of (TDAE)(O2SSSSO2)(s) containing the first polythionite, [O2SSSSO2]2-. AB - Gaseous SO2 reacts with tetrakis(dimethylamino)ethylene (TDAE) in acetonitrile in a 2:1 stoichiometric ratio to give analytically pure insoluble purple (TDAE)(O2SSO2) (1) in about 80% yield. Crystals of (TDAE)(O2SSSSO2) (2) were obtained from orange solution over the purple solid. The Raman spectrum of [TDAE](2+) was established using (TDAE)(A) salts [A = 2Br(-), 2Br(-).2H2O (X ray), 2[Br3](-) (X-ray)]. Vibrational spectroscopy showed that [O2SSO2](2-) in 1 has C2h geometry. The X-ray structure of 2 showed that it contained [O2SSSSO2](2 ), the first example of a new class of sulfur oxyanions, the polythionites. The geometry of [O2SSSSO2](2-) consists of S2 with an S-S bond length of 2.003(1) A connected to two terminal SO2 moieties by much longer S-S bonds of 2.337(1) A. Calculations (B3PW91/6-311+G(3df)) show that the structural units in [O2SSSSO2](2 ) are joined by the interaction of electrons in two mutually perpendicular pi* SOMOs of the triplet-state diradical S2 with unpaired electrons in the pi* antibonding orbitals of the two terminal [SO2](*-) and polarized to delocalize the negative charge equally onto the three fragments. Thermodynamic estimates show 2 to be stable with respect to loss of sulfur and formation of 1, in contrast to [O2SSSSO2](2-) salts of small cations that are unstable toward the related dissociation. Reaction of TDAE with an excess of liquid SO2 led to (TDAE)(O3SOSO3).SO2 (preliminary X-ray, Raman), (TDAE)(O3SSSSO3).2SO2 (preliminary X-ray, Raman), and (TDAE)(O3SSO2) (Raman). PMID- 24228762 TI - Promoting universal financial protection: evidence from seven low- and middle income countries on factors facilitating or hindering progress. AB - Although universal health coverage (UHC) is a global health policy priority, there remains limited evidence on UHC reforms in low- and middle-income countries (LMICs). This paper provides an overview of key insights from case studies in this thematic series, undertaken in seven LMICs (Costa Rica, Georgia, India, Malawi, Nigeria, Tanzania, and Thailand) at very different stages in the transition to UHC.These studies highlight the importance of increasing pre payment funding through tax funding and sometimes mandatory insurance contributions when trying to improve financial protection by reducing out-of pocket payments. Increased tax funding is particularly important if efforts are being made to extend financial protection to those outside formal-sector employment, raising questions about the value of pursuing contributory insurance schemes for this group. The prioritisation of insurance scheme coverage for civil servants in the first instance in some LMICs also raises questions about the most appropriate use of limited government funds.The diverse reforms in these countries provide some insights into experiences with policies targeted at the poor compared with universalist reform approaches. Countries that have made the greatest progress to UHC, such as Costa Rica and Thailand, made an explicit commitment to ensuring financial protection and access to needed care for the entire population as soon as possible, while this was not necessarily the case in countries adopting targeted reforms. There also tends to be less fragmentation in funding pools in countries adopting a universalist rather than targeting approach. Apart from limiting cross-subsidies, fragmentation of pools has contributed to differential benefit packages, leading to inequities in access to needed care and financial protection across population groups; once such differentials are entrenched, they are difficult to overcome. Capacity constraints, particularly in purchasing organisations, are a pervasive problem in LMICs. The case studies also highlighted the critical role of high-level political leadership in pursuing UHC policies and citizen support in sustaining these policies.This series demonstrates the value of promoting greater sharing of experiences on UHC reforms across LMICs. It also identifies key areas of future research on health care financing in LMICs that would support progress towards UHC. PMID- 24228767 TI - Secular trends in new childhood epidemics: insights from evolutionary medicine. AB - In the last few decades, pediatric medicine has observed a dramatic increase in the prevalence of hitherto rare illnesses, among which obesity, diabetes, allergies and other autoimmune diseases stand out. In addition, secular trends towards earlier onset of puberty and sexual activity contribute to the psychological problems of youth and adolescents. All this has occurred in spite of the improved health care provision for children, yet traditional concepts of medicine have failed to explain these new "epidemics". A recent conference and science school of the European Society of Paediatric Endocrinology (ESPE) in Acre, Israel, has taken up this challenge. Experts across disciplines including medicine, anthropology and developmental psychology discussed potential causes of childhood ill-health from an evolutionary point-of-view. Seen from an evolutionary vantage point, the "epidemics" of childhood obesity, diabetes and psychological dysfunction appear, in part, to be related to a mismatch between ancestral adaptations and novel environmental contingencies. These include changing exposures to pathogens, which impact on the function of the immune system, as well as changing patterns of parenting, which influence the timing of puberty and the risk for developing psychopathology. PMID- 24228768 TI - Editorial comment for Zumrutbas et al. PMID- 24228769 TI - Insulin resistance determined by Homeostasis Model Assessment (HOMA) and associations with metabolic syndrome among Chinese children and teenagers. AB - OBJECTIVE: The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk. METHODS: 3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS. RESULTS: With the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively. CONCLUSIONS: Our data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut-off points in this cohort were developed with variation regarding puberty. HOMA-IR may be useful for early evaluating insulin resistance in children and teenagers and could have a long-term benefit of preventive and diagnostic therapeutic intervention. PMID- 24228770 TI - Betrayal trauma and dimensions of borderline personality organization. AB - Borderline personality pathology can be conceptualized as one of many conditions within a broader spectrum of borderline personality organization (BPO). This spectrum is composed of several specific dimensions of psychological functioning (primitive psychological defenses, identity diffusion, and reality testing). Although several theories associate trauma with borderline pathology, betrayal trauma theory specifies that trauma with a high degree of betrayal has an especially pernicious influence on borderline pathology. In addition, betrayal trauma theorists propose that constructs related to each BPO dimension are influenced by traumatic betrayal, but this has not yet been tested within the context of borderline pathology specifically. In this article, we examine the relation between trauma with varying levels of betrayal and the specific dimensions of BPO using a Bayesian approach to multiple regression. Results indicated that trauma with a high degree of betrayal was associated with each dimension of BPO, that medium betrayal trauma was associated with problems in reality testing, and that low betrayal trauma was associated with primitive psychological defenses. These effects differed by gender. Limitations of the study and directions for future research are also discussed. PMID- 24228771 TI - Management of acute upside-down stomach. AB - BACKGROUND: Upside-down stomach (UDS) is characterized by herniation of the entire stomach or most gastric portions into the posterior mediastinum. Symptoms may vary heavily as they are related to reflux and mechanically impaired gastric emptying. UDS is associated with a risk of incarceration and volvulus development which both might be complicated by acute gastric outlet obstruction, advanced ischemia, gastric bleeding and perforation. CASE PRESENTATION: A 32-year-old male presented with acute intolerant epigastralgia and anterior chest pain associated with acute onset of nausea and vomiting. He reported on a previous surgical intervention due to a hiatal hernia. Chest radiography and computer tomography showed an incarcerated UDS. After immediate esophago-gastroscopy, urgent laparoscopic reduction, repair with a 360 degrees floppy Nissen fundoplication and insertion of a gradually absorbable GORE(r) BIO-A(r)-mesh was performed. CONCLUSION: Given the high risk of life-threatening complications of an incarcerated UDS as ischemia, gastric perforation or severe bleeding, emergent surgery is indicated. In stable patients with acute presentation of large paraesophageal hernia or UDS exhibiting acute mechanical gastric outlet obstruction, after esophago-gastroscopy laparoscopic reduction and hernia repair followed by an anti-reflux procedure is suggested. However, in cases of unstable patients open repair is the surgical method of choice. Here, we present an exceptionally challenging case of a young patient with a giant recurrent hiatal hernia becoming clinically manifest in an incarcerated UDS. PMID- 24228772 TI - The validity of the Menopause-specific Quality of Life questionnaire in women with type 2 diabetes. AB - OBJECTIVES: To examine the validity and reliability of the Menopause-specific Quality of Life (MENQOL) questionnaire in a sample of women with diabetes in Malaysia, with the secondary aim of determining whether MENQOL domain scores were associated with depression and diabetes. METHODS: A total of 337 postmenopausal women (241 with diabetes, 96 controls) were evaluated. Construct validity was evaluated using principal components analysis (PCA) and comparing scale items against the mental component score of the Short Form-12 (SF-12 MCS), and against the Center for Epidemiologic Studies Depression Scale 10 (CES-D 10). Consistency assessment was conducted using Cronbach's alpha. RESULTS: The internal consistencies for the physical (PHS), psychosocial (PS), sexual (VSS) and vasomotor domains were 0.86, 0.79, 0.79 and 0.70, and 0.90 for the full scale of MENQOL. PCA revealed a four-factorial model. Diabetes and non-diabetes subjects experienced their first period (13.25 vs. 13.10 years, p = 0.680) and achieved menopause around the same age (49.35 vs. 48.87 years, p = 0.426). We found significant variations in the MENQOL's PHS and PS domain scores that could be explained by SF-12 PCS (25%) and SF-12 MCS (20%) sub-scales. The validity of the MENQOL domains was demonstrated through significant associations with the equivalent SF-12 MCS and PCS subscales. The PS domain of the MENQOL also predicted the likelihood of symptoms of depression (1.42, 95% confidence interval 1.01-2.02). CONCLUSIONS: This study confirms the validity and internal consistency of the MENQOL questionnaire for measuring quality of life in postmenopausal women with diabetes, suggesting that the instrument can be used to screen people for menopausal symptoms. PMID- 24228773 TI - The association of trefoil factor 3 gene polymorphisms and haplotypes with unexplained female infertility: molecular insights into TFF3 regulation in receptive phase endometrium. AB - Abstract This study examined the genetic variation within the gene trefoil factor 3 (TFF3) in relation to unexplained female infertility in a group of women where aberrant endometrial maturation was suspected. The study consisted of 113 women with a diagnosis of unexplained infertility and 289 healthy fertile volunteers. Five single nucleotide polymorphisms rs225439, rs533093, rs225361, rs11701143, and rs77436142 within TFF3 gene were analyzed using real-time PCR. The formed haplotype pattern within the TFF3 gene in relation to infertility was also assessed. TFF3 protein localization and expression in receptive stage endometrium at the time of implantation was measured in a subset of fertile (n = 7) and infertile (n = 12) women. Allele and genotype frequencies did not differ significantly between fertile and infertile women, nor did the formed haplotypes. TFF3 protein was expressed in all cell types in receptive stage endometria in fertile and infertile women. No significant association was observed between protein expression and analyzed genotypes. A significantly higher TFF3 expression in luminal epithelial cells was detected in women with unexplained infertility (p = 0.003). PMID- 24228774 TI - Prevalence of chronic kidney disease in diabetic adult out-patients in Tanzania. AB - BACKGROUND: The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described. METHODS: This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system. RESULTS: A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)]. CONCLUSIONS: Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly 1/4 of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications. PMID- 24228775 TI - An association between autumn birth and clozapine treatment in patients with schizophrenia: a population-based analysis. AB - BACKGROUND: Numerous studies on seasonality of birth and schizophrenia risk have been published but it is uncertain whether, among those with schizophrenia, refractory illness exhibits any predilection for birth month. We hypothesized and examined whether a season of birth effect was present in patients with schizophrenia with a history of clozapine treatment. METHOD: Using record linkage with Danish registers, we examined patients with schizophrenia born between 1950 and 1970, and between 1995 and 2009 and Cox regression analysis was used to examine season of birth in relation to history of clozapine treatment. RESULTS: In a study population corresponding to 60,062 person-years from 5328 individuals with schizophrenia of which 1223 (23%) received at least one clozapine prescription, birth in the autumn (September-November) was associated with clozapine treatment (HR = 1.24; 95% CI 1.07-1.46) when compared with birth in the spring (March-May). CONCLUSION: Although replication studies are needed, this is the first evidence from a nationwide study suggesting a possible season associated risk of clozapine treatment in schizophrenia. The reasons for this relationship remain to be further investigated but might be partially explained by early exposures such as winter flu season and low vitamin D levels. PMID- 24228776 TI - Health-related quality of life in alcohol dependence: a systematic literature review with a specific focus on the role of depression and other psychopathology. AB - BACKGROUND: Health-related quality of life (HRQOL) is considered a valid measure of treatment effectiveness in addictions. However, alcohol research has lagged behind other biomedical fields in using HRQOL outcomes as primary or secondary endpoints. Previous work has suggested that psychiatric co-morbidity may mediate the relationship between alcohol dependence and HRQOL. AIM: The goal was to summarize the literature on HRQOL and its domains in the context of alcohol dependence. A specific focus was on the impact of depression and other psychopathology on these areas of life. MATERIALS AND METHODS: A database search of MEDLINE and PsychINFO was performed within the scope of PARADISE (Psychosocial fActors Relevant to brAin DISorders in Europe); a European Commission funded coordination action. Using pre-defined eligibility criteria, 42 studies were identified. A systematic approach to data collection was employed. RESULTS AND CONCLUSIONS: Alcohol dependence was shown to affect overall HRQOL and its domains, including general health, physical and mental health, general and social functioning, activities of daily living, pain and sleep. The evidence demonstrating that alcohol dependence is a primary cause of impairments in overall HRQOL, general health, mental and physical health and social functioning was fairly strong. Treatment interventions helped improve HRQOL and its aforementioned domains. The reduction or cessation of alcohol use facilitated these improvements; however, it was not reported to be predictive of improvement in all instances where improvement was reported. Depression was associated with further decreases in HRQOL. Personality disorders contributed to the severity of social functioning impairment. PMID- 24228777 TI - Perfectionism and sense of coherence among patients with eating disorders. AB - BACKGROUND: There is a substantial body of research on eating disorders and perfectionism. Also there are several studies on eating disorders and sense of coherence (SOC), but studies regarding all three subjects are sparse. Perfectionism and the degree of SOC are considered central and aggravating aspects of psychiatric conditions, not least in relation to eating disorders. AIMS: The present study aimed to describe the relationship between perfectionism as operationalized by Garner in the Eating Disorder Inventory-2 and SOC as defined by Antonovsky in the SOC-29 scale. The hypothesis was that SOC should be negatively associated with perfectionism. METHODS: Data from the two self measuring instruments collected from 95 consecutively recruited eating disorder outpatients were analysed with descriptive and inferential statistics. RESULTS: The patients in the present study scored consistently with other Swedish eating disorder samples on the Perfectionism subscale in the Eating Disorder Inventory-2 (EDI-P) and on the SOC-29, indicating a higher degree of perfectionism and weaker SOC than normal population groups. Perfectionism was significantly correlated to SOC. The correlation was negative, confirming the study hypothesis. The hypothesis was further confirmed in a subgroup analysis comparing patients with different degrees of SOC related to their EDI-P scores. CONCLUSIONS: Perfectionism is associated with SOC in patients with eating disorders. CLINICAL IMPLICATIONS: The clinical implications derived from the study could be a recommendation to focus on the SOC in patients with an eating disorder with the hope of lowering the patients' perfectionism as well. PMID- 24228778 TI - A 2-year follow-up study of people with severe mental illness involved in psychosocial rehabilitation. AB - BACKGROUNDS. A focus on psychiatric rehabilitation in order to support recovery among persons with severe mental illness (SMI) has been given great attention in research and mental health policy, but less impact on clinical practice. Despite the potential impact of psychiatric rehabilitation on health and wellbeing, there is a lack of research regarding the model called the Psychiatric Rehabilitation Approach from Boston University (BPR). AIM: The aim was to investigate the outcome of the BPR intervention regarding changes in life situation, use of healthcare services, quality of life, health, psychosocial functioning and empowerment. METHODS: The study has a prospective longitudinal design and the setting was seven mental health services who worked with the BPR in the county of Halland in Sweden. In total, 71 clients completed the assessment at baseline and of these 49 completed the 2-year follow-up assessments. RESULTS: The most significant finding was an improved psychosocial functioning at the follow-up assessment. Furthermore, 65% of the clients reported that they had mainly or almost completely achieved their self-formulated rehabilitation goals at the 2 year follow-up. There were significant differences with regard to health, empowerment, quality of life and psychosocial functioning for those who reported that they had mainly/completely had achieved their self-formulated rehabilitation goals compared to those who reported that they only had to a small extent or not at all reached their goals. CONCLUSIONS: Our results indicate that the BPR approach has impact on clients' health, empowerment, quality of life and in particular concerning psychosocial functioning. PMID- 24228779 TI - Finnish norms for young children on the Strengths and Difficulties Questionnaire. AB - BACKGROUND: Early recognition of children's mental health problems is crucial. Although the Strengths and Difficulties Questionnaire (SDQ) is a commonly used screening method, further research is needed on its validity and norms for young children. AIMS: The aims of the study were to confirm the adjusted lower (normal/borderline) and upper (borderline/abnormal) cut-offs for the SDQ in a Finnish community sample of 4-9-year-old children, and to explore the SDQ's ability to identify the children with mental health problems. METHODS: Parents and teachers completed the SDQs (n = 2666). The Development and Well-Being Assessment (DAWBA) was administered to parents and teachers of 646 children. RESULTS: The overall participation rate was 57%. The suggested cut-offs for the SDQ total difficulties scale rated by parents and teachers were 2-5 points lower than the corresponding published British norms. The sensitivity for the total score normal/borderline cut-off (9/10) was 76% in the parent and 66% in the teacher reports and for the borderline/abnormal cut-off (11/12) 90% and 70% respectively. The respective specificity values were 69%, 63%, 74% and 66%. The area under curve (AUC) values of the higher cut-offs were good for parent (0.87) and satisfactory for teacher rated (0.76) total scores. The presence of a DAWBA rater assigned diagnosis in the abnormal group compared with the normal group was sixfold in the parent and threefold in the teacher reported SDQs. CONCLUSIONS: The suggested cut-offs were clearly lower than the British norms. Yet the properties of the method's discriminative validity were acceptable. Population specific norms, taking into account both the culture and children's age, seem necessary for screening and for international comparisons of the method's validity properties. PMID- 24228780 TI - The specificity of the Stroop interference score of errors to ADHD in boys. AB - The Stroop Interference Test is widely used to assess the inhibition function; however, divergent results have emerged from meta-analyses in children with ADHD. This has led to conflicting results as to whether the Stroop test detects the level of inhibition in these children. We hypothesized that the general approach to include interference scores depending on response time causes conflicting results, whereas recordings of errors may prove a superior measure of the inhibition function in children with ADHD. In the present study, 39 children with an ADHD diagnosis, two subgroups with and without another comorbid mental health disorder, were compared with respect to their interference scores of response time and errors with two subgroups of children with no ADHD. The two subgroups comprised 33 children with another mental health disorder other than ADHD and 56 children with no psychiatric disorder. The between-group analyses detected a multivariate, marginal main effect of an ADHD diagnosis on the Stroop interference scores, and a univariate main effect of an ADHD diagnosis on the interference score of errors. Further, only the interference score of errors predicted significantly the parent reported scores on the Inhibit scale from the Behavior Rating Inventory of Executive Function. These findings support that a Stroop interference score of errors is sensitive for inhibition problems in children with ADHD and encourages the use of Stroop versions including error recordings independent of response time. PMID- 24228781 TI - The role of antihistamines in the treatment of vasomotor rhinitis. AB - BACKGROUND: The pathogenesis of vasomotor rhinitis is not understood. It is unlikely that antihistamines, based on their H1 antagonist activity alone, would be effective in this disorder. METHODS: Nonetheless, at least one double-blind, placebo-controlled multicenter trial has found that intranasal azelastine relieves symptoms of this disorder better than placebo. The mechanism responsible for its beneficial effect in nonallergic rhinitis is unclear but probably relates to "anti-inflammatory/antiallergic" activities. RESULTS: Such mechanisms have been demonstrated for a number of different oral antihistamines, but often the concentrations required in vitro are higher than those that are normally achieved in vivo using recommended dosing. It has been postulated that intranasal administration, which can achieve high local levels, might be a factor responsible for enhancing the "anti-inflammatory/antiallergic" properties. CONCLUSIONS: Interpreting this information allows one to conclude that antihistamines may be potentially effective agents in vasomotor rhinitis, and are more likely to be so when administered intranasally, despite the fact that data documenting this beneficial effect are sparse. PMID- 24228782 TI - Learning lessons from cancer centers in low- and middle-income countries. AB - Infectious Agents and Cancer is introducing a new section on Cancer Centers in Low- and Middle-Income Countries intended to provide the oncology community with detailed information about lessons learned in cancer control in resource-limited settings. The growing burden of cancer and the high rates of infection-related cancers in Low- and Middle-Income Countries (LMICs) argue for exploring the successes and challenges of cancer centers in low-resource settings. Detailed analyses are needed on how successful cancer centers have developed and managed such key components as strategic partnerships, trained cancer professionals, sustainable funding, appropriate technology, and research capacity. Many examples exist wherein local cancer centers have made significant progress and as such, the series will provide a platform to showcase detailed features of cancer institutes in LMICs and provide valuable information for those seeking to replicate successful models and to help invigorate efforts to build cancer capacity. PMID- 24228783 TI - Analysis of medical use of carbon adsorbents in China and additional possibilities in this field achieved in Ukraine. AB - The review is devoted to analysis of the use of carbon sorbents for medicinal purposes in China and description of some innovative technologies in this field in Ukraine. The review underlines the presence of common roots of sorption therapy development in these two countries determined by pioneer works of Prof. T.M.S. Chang, created to the concept of artificial cells. High level of works of Chinese scientists on sorption purification of blood and combined extracorporeal methods has been mentioned. At the same time, by author's opinion, two other methods of sorption therapy, namely enterosorption and sorption therapy of wounds and burns, has not been properly developed in China. In the review, there are also described the essential results of Ukrainian scientists in the field of blood purification from protein-bound toxins and other harmful compounds what is important for treatment of many serious human pathologies, and also the important data on the use of oral sorbents and dressings from activated carbon materials, which could be considered as a useful addition to achievements of Chinese scientists in the field of the development and use of sorbents for medicinal purposes. PMID- 24228784 TI - Relative importance of climatic, geographic and socio-economic determinants of malaria in Malawi. AB - BACKGROUND: Malaria transmission is influenced by variations in meteorological conditions, which impact the biology of the parasite and its vector, but also socio-economic conditions, such as levels of urbanization, poverty and education, which impact human vulnerability and vector habitat. The many potential drivers of malaria, both extrinsic, such as climate, and intrinsic, such as population immunity are often difficult to disentangle. This presents a challenge for the modelling of malaria risk in space and time. METHODS: A statistical mixed model framework is proposed to model malaria risk at the district level in Malawi, using an age-stratified spatio-temporal dataset of malaria cases from July 2004 to June 2011. Several climatic, geographic and socio-economic factors thought to influence malaria incidence were tested in an exploratory model. In order to account for the unobserved confounding factors that influence malaria, which are not accounted for using measured covariates, a generalized linear mixed model was adopted, which included structured and unstructured spatial and temporal random effects. A hierarchical Bayesian framework using Markov chain Monte Carlo simulation was used for model fitting and prediction. RESULTS: Using a stepwise model selection procedure, several explanatory variables were identified to have significant associations with malaria including climatic, cartographic and socio economic data. Once intervention variations, unobserved confounding factors and spatial correlation were considered in a Bayesian framework, a final model emerged with statistically significant predictor variables limited to average precipitation (quadratic relation) and average temperature during the three months previous to the month of interest. CONCLUSIONS: When modelling malaria risk in Malawi it is important to account for spatial and temporal heterogeneity and correlation between districts. Once observed and unobserved confounding factors are allowed for, precipitation and temperature in the months prior to the malaria season of interest are found to significantly determine spatial and temporal variations of malaria incidence. Climate information was found to improve the estimation of malaria relative risk in 41% of the districts in Malawi, particularly at higher altitudes where transmission is irregular. This highlights the potential value of climate-driven seasonal malaria forecasts. PMID- 24228786 TI - Introduction highlights of the asthma summit 2009: beyond the guidelines. PMID- 24228785 TI - Multifractal application on electrocardiogram. AB - Multifractal detrended fluctuation analysis is applied to analyse the degree of disorders, complexity and irregularity based on scaling behaviour of electrocardiogram. Since this method is based on random walk theory, noise level due to imperfect measurement in recording is reduced and it can systematically eliminate trends of different orders. The essence of this method is to extract the fractal features in ECG which can reflect changes in adaptability of physiological processes and to classify the pathological conditions and can lead to successful diagnosis. Fractal analysis is, therefore, a promising diagnostic tool in cardiovascular disease diagnosis and evaluation. PMID- 24228787 TI - Sugar cane stillage: a potential source of natural antioxidants. AB - Biorefinery of sugar cane is the first economic activity of Reunion Island. Some sugar cane manufactured products (juice, syrup, molasses) have antioxidant activities and are sources of both phenolic compounds and Maillard Reaction Products (MRP). The study aimed to highlight the global antioxidant activity of sugar cane stillage and understand its identity. Chromatographic fractionation on Sephadex LH-20 resin allowed the recovery of a MRP-rich fraction, responsible for 58 to 66% of the global antioxidant activity according to the nature of the sugar cane stillage (DPPH test), and a phenolic compounds-rich fraction for 37 to 59% of the activity. A good correlation was recorded between the antioxidant activity of the sugar cane stillage and its content in total reducing compounds amount (Folin-Ciocalteu assay), among them 2.8 to 3.9 g/L of phenolic compounds (in 5 caffeoylquinic acid equivalent). Preliminary experiments by HPLC-DAD-MS allowed to identify several free phenolic acids and gave clues to identify esters of quinic acids. PMID- 24228788 TI - Metal-free synthesis of aryl ethers in water. AB - The first arylation of allylic and benzylic alcohols with diaryliodonium salts is reported. The reaction yields alkyl aryl ethers under mild and metal-free conditions. Phenols are arylated to diaryl ethers in good to excellent yields. The reaction employs diaryliodonium salts and sodium hydroxide in water at low temperature, and excess amounts of the coupling partners are avoided. PMID- 24228791 TI - Activation of a unique flavin-dependent tRNA-methylating agent. AB - TrmFO is a tRNA methyltransferase that uses methylenetetrahydrofolate (CH2THF) and flavin adenine dinucleotide hydroquinone as cofactors. We have recently shown that TrmFO from Bacillus subtilis stabilizes a TrmFO-CH2-FADH adduct and an ill defined neutral flavin radical. The adduct contains a unique N-CH2-S moiety, with a methylene group bridging N5 of the isoalloxazine ring and the sulfur of an active-site cysteine (Cys53). In the absence of tRNA substrate, this species is remarkably stable but becomes catalytically competent for tRNA methylation following tRNA addition using the methylene group as the source of methyl. Here, we demonstrate that this dormant methylating agent can be activated at low pH, and we propose that this process is triggered upon tRNA addition. The reaction proceeds via protonation of Cys53, cleavage of the C-S bond, and generation of a highly reactive [FADH(N5)?CH2]+ iminium intermediate, which is proposed to be the actual tRNA-methylating agent. This mechanism is fully supported by DFT calculations. The radical present in TrmFO is characterized here by optical and EPR/ENDOR spectroscopy approaches together with DFT calculations and is shown to be the one-electron oxidized product of the TrmFO-CH2-FADH adduct. It is also relatively stable, and its decomposition is facilitated by high pH. These results provide new insights into the structure and reactivity of the unique flavin dependent methylating agent used by this class of enzymes. PMID- 24228790 TI - N- versus C-domain selectivity of catalytic inactivation of human angiotensin converting enzyme by lisinopril-coupled transition metal chelates. AB - The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was tested for both reversible binding and irreversible catalytic inactivation of each domain of sACE-1. C/N domain binding selectivity ratios ranged from 1 to 350, while rates of irreversible catalytic inactivation of the N and C-domains were found to be significantly greater for the N-domain, suggesting a more optimal orientation of M-chelate-lisinopril complexes within the active site of the N-domain of sACE-1. Finally, the combined effect of binding selectivity and inactivation selectivity was assessed for each catalyst (double-filter selectivity factors), and several catalysts were found to cause domain-selective catalytic inactivation. The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and catalytic factors (double-filter effect). PMID- 24228792 TI - Rural and urban differences in blood pressure and pregnancy-induced hypertension among pregnant women in Ghana. AB - BACKGROUND: Globally, about 350.000 women die every year from pregnancy related causes and more than half of these deaths occur in sub-Saharan Africa (SSA). Approximately 12% of the maternal deaths are associated with hypertensive disorders in pregnancy such as pregnancy induced hypertension (PIH). However, very little is known about PIH and associated determinants in many SSA countries such as Ghana. We therefore sought to assess rural and urban differences in blood pressure (BP) and PIH among pregnant women in Ghana. METHODS: We conducted a cross-sectional study among 967 rural (677) and urban (290) pregnant women with a gestational age of more than 20 weeks. PIH was defined as a systolic blood pressure of >=140 mmHg and/or diastolic blood pressure of >=90 mmHg. RESULTS: Women in urban Ghana had a higher mean systolic and diastolic BP than women in rural Ghana (105/66 mmHg versus 102/61 mmHg, p < 0.001 for both systolic and diastolic BP). The prevalence of PIH was also higher in urban Ghana (3.1%) than in rural Ghana (0.4%) (p = 0.014). The urban and rural difference in mean diastolic blood pressure persisted even after adjustments for the study characteristics in a linear regression model. In both rural and urban Ghana, BMI, heart rate and a family history of hypertension were independently associated with BP. CONCLUSION: Our findings suggest higher mean BP levels and PIH in urban Ghana than in rural Ghana. BMI was independently related to high BP. Left unchecked, the increasing prevalence of overweight and obesity in Ghana will exacerbate PIH levels in Ghana. PMID- 24228793 TI - Diversity of methanogens in the hindgut of captive white rhinoceroses, Ceratotherium simum. AB - BACKGROUND: The white rhinoceros is on the verge of extinction with less than 20,200 animals remaining in the wild. In order to better protect these endangered animals, it is necessary to better understand their digestive physiology and nutritional requirements. The gut microbiota is nutritionally important for herbivorous animals. However, little is known about the microbial diversity in the gastrointestinal tract (GIT) of the white rhinoceros. Methanogen diversity in the GIT may be host species-specific and, or, function-dependent. To assess methanogen diversity in the hindgut of white rhinoceroses, an archaeal 16S rRNA gene clone library was constructed from pooled PCR products obtained from the feces of seven adult animals. RESULTS: Sequence analysis of 153 archaeal 16S rRNA sequences revealed 47 unique phylotypes, which were assigned to seven operational taxonomic units (OTUs 1 to 7). Sequences assigned to OTU-7 (64 out of 153 total sequencs - 42%) and OTU-5 (18%, 27/153) had 96.2% and 95.5% identity to Methanocorpusculum labreanum, respectively, making Methanocorpusculum labreanum the predominant phylotype in these white rhynoceroses. Sequences belonging to OTU 6 (27%, 42/153) were related (97.6%) to Methanobrevibacter smithii. Only 4% of the total sequences (6/153) were assigned to Methanosphaera stadtmanae (OTU-1). Sequences belonging to OTU-2 (4%, 6/153), OTU-3 (3%, 5/153) and OTU-4 (2%, 3/153) were distantly related (87.5 to 88,4%) to Methanomassiliicoccus luminyensis and were considered to be novel species or strains that have yet-to-be cultivated and characterized. CONCLUSION: Phylogenetic analysis indicated that the methanogen species in the hindgut of white rhinoceroses were more similar to those in the hindgut of horses. Our findings may help develop studies on improving the digestibility of forage for sustainable management and better health of these endangered animals. PMID- 24228794 TI - Development of catalysts and ligands for enantioselective gold catalysis. AB - During the past decade, the use of Au(I) complexes for the catalytic activation of C-C pi-bonds has been investigated intensely. Over this time period, the development of homogeneous gold catalysis has been extraordinarily rapid and has yielded a host of mild and selective methods for the formation of carbon-carbon and carbon-heteroatom bonds. The facile formation of new bonds facilitated by gold naturally led to efforts toward rendering these transformations enantioselective. In this Account, we survey the development of catalysts and ligands for enantioselective gold catalysis by our research group as well as related work by others. We also discuss some of our strategies to address the challenges of enantioselective gold(I) catalysis. Early on, our work with enantioselective gold-catalyzed transformations focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, the careful choice of the weakly coordinating ligand (or counterion) was necessary to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In general, these tactics enhance the steric influence around the reactive gold center beyond the two coordinate ligand environment. The use of binuclear complexes allowed us to use the second gold center and its associated ligand (or counterion) to exert a further steric influence. In a similar vein, we employed a chiral anion (in place of or in addition to a chiral ligand) to move the chiral information closer to the reactive center. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, we also developed a new class of mononuclear phosphite and phosphoramidite ligands to supplement the previously widely utilized phosphines. However, we needed to judiciously design the steric environment to create "walls" that enclose the gold center. We also successfully applied these same considerations to the development of binuclear carbene ligands for gold. Finally, we describe the design of bifunctional urea-monophosphine ligands used in a gold catalyzed three-component coupling. PMID- 24228795 TI - Urological research in sub-Saharan Africa: a retrospective cohort study of abstracts presented at the Nigerian Association of Urological Surgeons conferences. AB - BACKGROUND: Nigeria is one of the top three countries in Africa in terms of science research output and Nigerian urologists' biomedical research output contributes to this. Each year, urologists in Nigeria gather to present their recent research at the conference of the Nigerian Association of Urological Surgeons (NAUS). These abstracts are not thoroughly vetted as are full length manuscripts published in peer reviewed journals but the information they disseminate may affect clinical practice of attendees. This study aims to describe the characteristics of abstracts presented at the annual conferences of NAUS, the quality of the abstracts as determined by the subsequent publication of full length manuscripts in peer-review indexed journals and the factors that influence such successful publication. METHODS: Abstracts presented at the 2007 to 2010 NAUS conferences were identified through conference abstracts books. Using a strict search protocol, publication in peer-reviewed journals was determined. The abstracts characteristics were analyzed and their quality judged by subsequent successful publishing of full length manuscripts. Statistical analysis was performed using SPSS 16.0 software to determine factors predictive of successful publication. RESULTS: Only 75 abstracts were presented at the NAUS 2007 to 2010 conferences; a quarter (24%) of the presented abstracts was subsequently published as full length manuscripts. Median time to publication was 15 months (range 2-40 months). Manuscripts whose result data were analyzed with 'beyond basic' statistics of frequencies and averages were more likely to be published than those with basic or no statistics. CONCLUSIONS: Quality of the abstracts and thus subsequent publication success is influenced by the use of 'beyond basic' statistics in analysis of the result data presented. There is a need for improvement in the quality of urological research from Nigeria. PMID- 24228796 TI - Promoting universal financial protection: health insurance for the poor in Georgia--a case study. AB - BACKGROUND: The present study focuses on the program "Medical Insurance for the Poor (MIP)" in Georgia. Under this program, the government purchased coverage from private insurance companies for vulnerable households identified through a means testing system, targeting up to 23% of the total population. The benefit package included outpatient and inpatient services with no co-payments, but had only limited outpatient drug benefits. This paper presents the results of the study on the impact of MIP on access to health services and financial protection of the MIP-targeted and general population. METHODS: With a holistic case study design, the study employed a range of quantitative and qualitative methods. The methods included document review and secondary analysis of the data obtained through the nationwide household health expenditure and utilisation surveys 2007 2010 using the difference-in-differences method. RESULTS: The study findings showed that MIP had a positive impact in terms of reduced expenditure for inpatient services and total household health care costs, and there was a higher probability of receiving free outpatient benefits among the MIP-insured. However, MIP insurance had almost no effect on health services utilisation and the households' expenditure on outpatient drugs, including for those with MIP insurance, due to limited drug benefits in the package and a low claims ratio. In summary, the extended MIP coverage and increased financial access provided by the program, most likely due to the exclusion of outpatient drug coverage from the benefit package and possibly due to improper utilisation management by private insurance companies, were not able to reverse adverse effects of economic slow down and escalating health expenditure. MIP has only cushioned the negative impact for the poorest by decreasing the poor/rich gradient in the rates of catastrophic health expenditure. CONCLUSIONS: The recent governmental decision on major expansion of MIP coverage and inclusion of additional drug benefit will most likely significantly enhance the overall MIP impact and its potential as a viable policy instrument for achieving universal coverage. The Georgian experience presented in this paper may be useful for other low- and middle-income countries that are contemplating ways to ensure universal coverage for their populations. PMID- 24228797 TI - Vitamin D status in diabetic Egyptian children and adolescents: a case-control study. AB - BACKGROUND: Recently, studies suggesting that vitamin D deficiency correlates with the severity and frequency of Type 1 (insulin-dependent) diabetes mellitus (T1DM) and that vitamin D supplementation reduces the risk of developing T1DM have been reported. OBJECTIVE: In this study, we aimed to assess vitamin D status in Egyptian children and adolescents with T1DM. METHODS: This was a case-control study including 80 T1DM diagnosed cases aged 6 to 16 years and 40 healthy children with comparable age and gender as the control group. For all subjects, serum 25 (OH) D levels were measured by ELISA, Serum parathyroid hormone (PTH) and serum insulin were measured by an electrochemiluminesce immunoassay. Serum glucose, Glycosylated hemoglobin (HbA1c) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were also assessed. RESULTS: Compared to the control group, serum vitamin D levels were not significantly lower in diabetic subjects (24.7 +/- 5.6 vs 26.5 +/- 4.8 ng/ml; P > 0.05). Among diabetic cases 44(55%) were vitamin D deficient; meanwhile 36(45%) cases had normal vitamin D level (P < 0.01). In addition, 26(32.5%) diabetic cases had 2ry hyperparathyroidism and 54(67.5%) cases had normal parathyroid hormone level; meanwhile, none of the control group had 2ry hyperparathyroidism (P < 0.01). Furthermore, we found a significant difference between vitamin D deficient diabetic cases and those with normal vitamin D level as regards HOMA-IR and diabetes duration (P < 0.01). CONCLUSION: Public health message on the importance of vitamin D status; especially in diabetic children and adolescents, should be disseminated to the public. PMID- 24228798 TI - Dissociative depression among women with fibromyalgia or rheumatoid arthritis. AB - The aim of this study was to inquire about the possible relations of childhood trauma, anger, and dissociation to depression among women with fibromyalgia or rheumatoid arthritis. Fifty female patients diagnosed as having fibromyalgia (n = 30) or rheumatoid arthritis (n = 20) participated in the study. The Childhood Trauma Questionnaire, Somatoform Dissociation Questionnaire (SDQ), Dissociation Questionnaire (DIS-Q), Beck Depression Inventory (BDI), Spielberger State-Trait Anger Expression Inventory, and Dissociative Disorders Interview Schedule were administered to all participants. Women with a lifetime diagnosis of depressive disorder had higher scores for somatoform and psychoform dissociation than the nondepressive patients. However, childhood trauma scores did not differ between the 2 groups. In regression analysis, current severity of depression (BDI) was predicted by psychoform dissociation (DIS-Q) and lower education, and lifetime diagnosis of major depression was predicted by somatoform dissociation (SDQ). Whereas childhood emotional neglect predicted somatoform dissociation, psychoform dissociation was predicted by childhood sexual abuse. Mental processing of anger seems to be 1 of the dimensions of psychodynamics in trauma-related depressive conditions. In the context of the perceived threat of loss of control due to expressed anger and mental disintegration, somatoform dissociation seems to contribute to overmodulation of emotions in dissociative depression. Among patients suffering from physical illness with possible psychosomatic dimensions, assessment of somatoform dissociation in addition to psychoform dissociation may be helpful to understand diverse psychopathological trajectories emerging in the aftermath of childhood adversities. The recently proposed category of "dissociative depression" (Sar, 2011) seems to be a promising concept for future research on psychosomatic aspects of traumatic stress. PMID- 24228799 TI - Structure and magnetic properties of the alpha-NaFeO2-type honeycomb compound Na3Ni2BiO6. AB - We present the structure and magnetic properties of Na3Ni2BiO6, which is an ordered variant of the alpha-NaFeO2 structure type. This layered compound has a 2:1 ordering of (Ni(2+)/Bi(5+))O6 octahedra within the a-b plane and sodium in octahedra between the layers. The structure is presented in the space group C2/m, determined through a combination of single crystal X-ray, powder neutron, and powder X-ray diffraction. Temperature dependent magnetic susceptibility measurements show Na3Ni2BiO6 to display long-range antiferromagnetic ordering below 11 K, despite the dominance of ferromagnetic interactions above TN as indicated by a positive Weiss constant. Heat capacity measurements and low temperature neutron diffraction support the magnetic ordering and are consistent with a TN of 10.4 K. A magnetic phase can be refined with (010) antiferromagnetic ordering along the b-axis in the honeycomb layer and moments aligned parallel to c. The compounds Na3Mg2BiO6 and Na3Zn2BiO6, synthesized as nonmagnetic analogues of Na3Ni2BiO6, are briefly described. PMID- 24228801 TI - Memory coding in individuals with Down syndrome. AB - Previous research has identified a deficit in phonological short-term memory in individuals with Down syndrome. The present work aimed to analyze how a group of 30 individuals with Down syndrome performed in a picture span task compared with 30 typically developing children of the same mental age. The task involved four conditions (i.e., dissimilar, phonologically similar, visually similar, and long name items) chosen to analyze the strategy used by individuals with Down syndrome to code visually presented nameable items. Individuals with Down syndrome performed less well than typically developing children. Both groups showed the visual similarity effect. Taken together, our results confirm that individuals with Down syndrome have a verbal working memory deficit, even when nameable items are presented visually. Mental age appears to be an important determinant of memory coding stage in individuals with Down syndrome. PMID- 24228800 TI - Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. AB - BACKGROUND: Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease. METHODS: Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm. RESULTS: The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity. CONCLUSIONS: Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance. PMID- 24228802 TI - Editorial comment for Alloussi et al. PMID- 24228803 TI - Blood lipids profile in hyperlipidemic children undergoing different dietary long chain polyunsaturated supplementations: a preliminary clinical trial. AB - The aim of this preliminary study was to explore the effect size of different dietary long chain polyunsaturated supplementations on blood lipid profile in children with primary hyperlipidemia. Thirty-six children (8-13 years) were recruited. After an 8-week stabilization period on the Step I diet, they were randomized to additionally receive for a 16-week period one capsule (500 mg) daily of docosahexaenoic acid (DHA) alone or a DHA plus eicosapentaenoic acid (EPA) mixture (45.6% DHA; 41.6% EPA) or wheat germ oil (control). An effect size (as percentage change from baseline) of +8%, -12% and -16% for high-density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C ratio and triglycerides was observed in children supplemented with DHA, compared to +2%, -8% and -12%, respectively, in children supplemented with DHA plus EPA. This preliminary study suggests powered trials appear feasible and are warranted to evaluate efficacy of n-3 long-chain polyunsaturated fatty acid dietary supplementations on the blood lipid profile of children with primary hyperlipidemia. PMID- 24228804 TI - RETRACTED: Bone mineral density of lumbar spine and femur in patients with gynecologic cancer. AB - Objective To compare the bone mineral density (BMD) of the lumbar spine and femur in postmenopausal women with cervical and endometrial cancer without bone metastasis with that in normal control postmenopausal women Methods We retrospectively analyzed the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry in 130 patients with cervical cancer, 68 patients with endometrial cancer, and 225 healthy controls. Results The serum levels of calcium, phosphorus, osteocalcin, total alkaline phosphatase and urine deoxypyridinoline were measured in all participants. Age, body mass index, parity and time since menopause were not significantly different between the three groups. The T-scores of basal BMD at the fourth lumbar vertebra (L4) were significantly lower in patients with cervical cancer (- 0.68 +/- 0.10) compared to those in the other two groups. Additionally, the incidence of osteoporosis at L4 according to the basal status of bone mass was significantly higher in patients with cervical cancer (10.0%) compared to that in controls (0.4%). Urine deoxypyridinoline levels were significantly higher in patients with cervical cancer compared to those in controls. No differences in basal BMD of the lumbar spine and femur were observed between patients with endometrial cancer and controls, and no significant differences in biochemical markers were detected between patients with endometrial cancer and controls. Conclusion Our results suggest that postmenopausal women with cervical cancer have a lower BMD and are at increased risk of osteoporosis in the lumbar spine before receiving anticancer treatment compared with postmenopausal women with endometrial cancer. PMID- 24228805 TI - Prevalence and predictors of Cervical Intraepithelial Neoplasia among HIV infected women at Bugando Medical Centre, Mwanza-Tanzania. AB - INTRODUCTION: Cancer of the cervix rank the second most common cause of cancer related deaths among women in Sub-Saharan Africa. It is estimated that 529, 409 new cases are diagnosed annually with a mortality rate approaching 274,883 per year. Cervical Intraepithelial Neoplasia (CIN) precedes almost all cervical cancers. The incidence rate of CIN among HIV infected women is five times higher as compared to the rate in HIV negative women. The screening for cervical dysplasia and an appropriate management in women with CIN are effective methods for preventing cervical cancer. This study was done to determine the prevalence and predictors of CIN among a HIV infected women attending Care and Treatment centre (CTC) at Bugando Medical Centre (BMC). METHODS: A cross sectional survey was undertaken among HIV infected women aged 18 years and above attending at BMC CTC clinic between February and March 2013. Visual Inspection with Acetic acid (VIA) was used as the screening method for detection of CIN. Socio-demographic, reproductive and clinical information was obtained from participants and the blood was collected for CD4 lymphocyte count. Cervical punch biopsy for histological examination was performed for those who had VIA positive test. Data were entered and analyzed using STATA Version 12.0 soft ware. RESULTS: A total number of 95 (26.8%) participants had positive VIA test among three hundred and fifty-five (355) HIV infected women. Histology results showed; 4(4.2%) were normal, 26 (27.4%) had an inflammatory lesion, 58(61.1%) had CIN and 7(7.3%) had invasive cervical cancer. CIN was found to be associated with a history of multiple sexual partners (P<0.001), a history of genital warts (P<0.001), and a history of STI (P = 0.010). CONCLUSION: The Cervical Intraepithelial Neoplasia is a problem among HIV infected women. A history of multiple sexual partners, a history of genital warts, a history STI and a low baseline CD4 T lymphocyte were significant predictors for CIN. Screening for Cervical Intraepithelial Neoplasia is recommended for all women with HIV. PMID- 24228806 TI - Susceptibility to ATP depletion of primary proximal tubular cell cultures derived from mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK. AB - BACKGROUND: The purpose of this study was to determine whether AMPK influences the survival of primary cultures of mouse proximal tubular (MPT) cells subjected to metabolic stress. Previous studies, using an immortalized MPT cell line, suggest that AMPK is activated during metabolic stress, and ameliorates stress induced apoptosis of these cells. METHODS: Primary MPT cells were cultured from AMPK knockout (KO) mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK. MPT cells were subjected to ATP depletion using antimycin A. RESULTS: Surprisingly, there was no difference in the amount of death induced by metabolic stress of MPT cells from either type of AMPK KO mice compared to its WT control. Moreover, inhibition of the activity of the alpha1 isoform in primary MPT cells from alpha2-/- mice (pharmacologically, via compound C) or inhibition of the alpha2 isoform in primary MPT cells from alpha1-/- mice (molecularly, via knockdown) both decreased cell viability equivalently in response to metabolic stress. The explanation for this unexpected result appears to be an adaptive increase in expression of the non-deleted alpha-isoform. As a consequence, total alpha-domain expression (i.e. alpha1 + alpha2), is comparable in kidney cortex and in cultured MPT cells derived from either type of KO mouse versus its WT control. Importantly, each alpha-isoform appears able to compensate fully for the absence of the other, with respect to both the phosphorylation of downstream targets of AMPK and the amelioration of stress-induced cell death. CONCLUSIONS: These findings not only confirm the importance of AMPK as a pro survival kinase in MPT cells during metabolic stress, but also show, for the first time, that each of the two alpha-isoforms can substitute for the other in MPT cells from AMPK KO mice with regard to amelioration of stress-induced loss of cell viability. PMID- 24228807 TI - Associations between smoking, components of metabolic syndrome and lipoprotein particle size. AB - BACKGROUND: The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) may be altered in MetS. This study aimed to examine the association between smoking and the following parameters: MetS and its components, levels of apolipoproteins and estimated lipoprotein particle size, separately for men and women, and in different body mass index (BMI) classes. METHODS: We included 24,389 men and 35,078 women aged between 18 and 80 years who participated in the LifeLines Cohort Study between December 2006 and January 2012; 5,685 men and 6,989 women were current smokers. Participants were categorized into three different body mass index (BMI) classes (BMI <25; BMI 25 to 30; BMI >=30 kg/m2). MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP:ATPIII) criteria. Blood pressure, anthropometric and lipid measurements were rigorously standardized, and the large sample size enabled a powerful estimate of quantitative changes. The association between smoking and the individual MetS components, and apoA1 and apoB, was tested with linear regression. Logistic regression was used to examine the effect of smoking and daily tobacco smoked on risk of having MetS. All models were age adjusted and stratified by sex and BMI class. RESULTS: Prevalence of MetS increased with higher BMI levels. A total of 64% of obese men and 42% of obese women had MetS. Current smoking was associated with a higher risk of MetS in both sexes and all BMI classes (odds ratio 1.7 to 2.4 for men, 1.8 to 2.3 for women, all P values <0.001). Current smokers had lower levels of HDL cholesterol and apoA1, higher levels of triglycerides and apoB, and higher waist circumference than non-smokers (all P <0.001). Smoking had no consistent association with blood pressure or fasting blood glucose. In all BMI classes, we found a dose-dependent association of daily tobacco consumption with MetS prevalence as well as with lower levels of HDL cholesterol, higher triglyceride levels and lower ratios of HDL cholesterol/apoA1 and, only in those with BMI <30, LDL cholesterol/apoB (all P <0.001). CONCLUSIONS: Smoking is associated with an increased prevalence of MetS, independent of sex and BMI class. This increased risk is mainly related to lower HDL cholesterol, and higher triglycerides and waist circumference. In addition, smoking was associated with unfavorable changes in apoA1 and apoB, and in lipoprotein particle size. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/196. PMID- 24228808 TI - miR-584 expressed in human gingival epithelial cells is induced by Porphyromonas gingivalis stimulation and regulates interleukin-8 production via lactoferrin receptor. AB - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that are involved in post-transcriptional regulation of gene expression. Differential miRNA expression in innate and acquired immunity has been shown to regulate immune cell development and function. miRNA expression has been demonstrated to affect pathophysiology of inflammatory diseases, such as rheumatoid arthritis and lupus. As such, this study explores the role of miRNA in the context of pathophysiology of destructive periodontitis. Specifically, this investigation profiles the differentially expressed miRNA of Porphyromonas gingivalis (Pg)-stimulated human gingival epithelial cells (HGECs). METHODS: The specific miRNAs differentially expressed in Pg-stimulated OBA-9, immortalized HGECs, were analyzed using microarray. Real-time polymerase chain reaction (PCR) and Western blotting were performed to confirm the level of miRNA expression and determine target production of miRNA in OBA-9. The production of interleukin (IL)-8 was measured to determine the bioactivity of target protein regulated by miRNA. RESULTS: miR 584, which targets lactoferrin receptor (LfR), was 3.39-fold upregulated by Pg stimulation. This upregulation of miR-584 was confirmed by real-time PCR. Pg stimulation resulted in the suppression of LfR at mRNA and protein levels. The transfection of the miR inhibitor for miR-584 in OBA-9 recovered Pg-induced suppression of LfR. The addition of human lactoferrin (hLf) had a suppressive effect on IL-8 production in Pg-stimulated OBA-9. However, hLf also decreased IL 8 production strongly in Pg-stimulated OBA-9 in the presence of the miR inhibitor for miR-584. CONCLUSION: These findings suggest that the upregulation of miR-584 by Pg in OBA-9 inhibits the anti-inflammatory effects of hLf via the suppression of LfR. PMID- 24228809 TI - Salivary visfatin concentrations in patients with chronic periodontitis. AB - BACKGROUND: Visfatin, also known as pre-B-cell colony-enhancing factor, is secreted from a variety of cells and is thought to have some proinflammatory and immunomodulating effects. It is indicated that serum/plasma levels of visfatin increase in a number of inflammatory disorders. The present study aims to evaluate salivary concentrations of visfatin in patients with chronic periodontitis (CP). METHODS: Twenty patients with CP and 20 periodontally healthy individuals were enrolled in this study. For each patient, the values of clinical parameters, such as bleeding index, plaque index, probing depth, and clinical attachment level (CAL), were recorded. Whole saliva samples were collected, and concentrations of visfatin were evaluated using standard enzyme-linked immunosorbent assay. Statistical analysis was performed using statistical software. RESULTS: Visfatin was detectable in all samples. Salivary visfatin concentrations were significantly higher in the periodontitis group. In addition, there was a positive significant relationship between salivary visfatin concentrations and CAL in the periodontitis group. However, no significant association was observed between salivary visfatin levels and other periodontal parameters or body mass index. CONCLUSION: These results indicate that there is a relationship between salivary visfatin and CP; however, further studies are needed to confirm this finding. PMID- 24228810 TI - An NMR and MD modeling insight into nucleation of 1,2-alkanediols: selective crystallization of lipase-catalytically resolved enantiomers from the reaction mixtures. AB - The work on developing a scalable lipase-catalytic method for the kinetic resolution of long-chain 1,2-alkanediols, complemented by crystallization of the pure enantiomers from the reaction mixtures, offered the possibility of a more detailed study of the aggregation of such diols. MD modeling, mass spectrometry, (1)H NMR, and DOSY studies provided a novel insight into the nucleation process. An efficient protocol for stereo- and chemoselective crystallization of (S)-1,2 dodecanediol and related compounds from the crude bioconversion mixtures was developed. PMID- 24228811 TI - No asymptomatic malaria parasitaemia found among 108 young children at one health facility in Dar es Salaam, Tanzania. AB - BACKGROUND: Asymptomatic malaria parasitaemia has been reported in areas with high malaria transmission. It may serve as a reservoir for continued transmission, and furthermore complicates diagnostics, as not all individuals with a positive malaria test are necessarily ill due to malaria, although they may present with malaria-like symptoms. Asymptomatic malaria increases with age as immunity to malaria gradually develops. As mortality and morbidity of malaria is higher among younger children it is important to know the prevalence of asymptomatic malaria parasitaemia in this population in order to interpret laboratory results for malaria correctly. METHODS: A total of 108 children that had neither been treated for malaria nor had a fever the previous four weeks were recruited consecutively at a maternal and child health clinic (MCHC) in Dar es Salaam, Tanzania. A rapid diagnostic test (RDT) for malaria and dried blood spot (DBS) on filter paper were taken from each child. Social and clinical data were recorded. DNA was extracted from the DBS of study participants by a method using InstaGeneTM matrix. PCR targeting the Plasmodium mitochondrial genome was performed on all samples. RESULTS: Median age was 4.6 months (range 0.5-38). All the RDTs were negative. PCR was negative for all study subjects. CONCLUSION: The study suggests that asymptomatic malaria may not be present in apparently healthy children up to the age of three years in Dar es Salaam, Tanzania. However, because of the small sample size and low median age of the study population, the findings cannot be generalized. Larger studies, including higher age groups, need to be done to clarify whether asymptomatic malaria parasitaemia is present in the general population in the Dar es Salaam area. PMID- 24228812 TI - Dissolvable bridges for manipulating fluid volumes in paper networks. AB - A capability that is key to increasing the performance of paper microfluidic devices is control of fluid transport in the devices. We present dissolvable bridges as a novel method of manipulating fluid volumes within paper-based devices. We demonstrate and characterize the operation of the bridges, including tunability of the volumes passed from 10 MUL to 80 MUL, using parameters such as geometry and composition. We further demonstrate the utility of dissolvable bridges in the important context of automated delivery of different volumes of a fluid from a common source to multiple locations in a device for simple device loading and activation. PMID- 24228813 TI - Anticholinergic drugs in nonallergic rhinitis. AB - BACKGROUND: The parasympathetic nervous system contributes to the pathophysiology of multiple forms of allergic and nonallergic rhinitis. Stimulation of the parasympathetic nervous system leads to glandular activation, which produces watery secretions. In excess, these secretions discharge from the anterior Nares and produce the symptom of watery anterior rhinorrhea. METHOD: Review of literature. RESULTS: Treatment with topical, intranasal anticholinergic drugs inhibits activation of the nasal mucosal glands and is effective in reducing the watery secretions associated with parasympathetic stimulation of the glands with little, if any, effect on the symptoms of congestion and sneezing. In general, these drugs have no systemic adverse effects, but can cause crusting and local irritation. CONCLUSION: Anticholinergic drugs are useful for the treatment of anterior rhinorrhea associated with allergic and nonallergic rhinitis. PMID- 24228814 TI - Petromyzonin, a hexahydrophenanthrene sulfate isolated from the larval sea lamprey (Petromyzon marinus L.). AB - A new hexahydrophenanthrene sulfate was identified from water conditioned with sea lamprey larvae ( Petromyzon marinus ) and named petromyzonin. Its structure was unequivocally elucidated on the basis of spectroscopic analyses including comparison with spectra of known compounds. The absolute configuration was determined by electronic circular dichroism. Petromyzonin may function as a chemical signal, as it elicited responses in electro-olfactogram recording with a dynamic concentration-response relationship and a detection threshold of 10(-11) M. PMID- 24228815 TI - Section 1. EPR-3 versus GINA 2008 Guidelines - Asthma Control and Step 3 Care: Highlights of the Asthma Summit 2009: Beyond the Guidelines. AB - Recent updates to asthma guidelines from the Global Initiative for Asthma (GINA) and the National Asthma Education and Prevention Program (Expert Panel Report 3, EPR-3) share many similarities, reflecting a focus on asthma control based on clinical manifestations of disease and responsiveness to therapy. Both documents build upon the recommendations of former guidelines utilizing evidence-based review of the published literature to revise algorithms for practice. A major difference between the 2 reports is the preferred treatment at Step 3. The GINA guidelines recommend a combination of low-dose inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA), whereas the EPR-3 advises either monotherapy with medium-dose ICS or the low-dose ICS + LABA combination. Both approaches are supported by clinical experience and Level A evidence. The option of personalized therapy is a point of discussion for future guidelines. PMID- 24228816 TI - 'Suspect molecular signature' in blood as the indicator of undiagnosed breast cancer, cancer risk and targeted prevention. AB - BACKGROUND: Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer types. Further, high levels of circulating tumour cells are a characteristic of breast cancer patients demonstrating a particular predisposition to the development of breast cancer metastatic disease. Actual diagnostic approaches are frequently unable to recognise early stages of tumour development which impairs individual outcomes. In contrast, predictive and preventive risk assessment and early diagnosis may lead to full recovery after surgical resection. Recently, the authors have reported about the construction of diagnostic windows, which could influence the molecular diagnostics of breast cancer. MATERIAL AND METHODS: In a previous study, diagnostic windows for breast cancer risk assessment were analysed. Women with non-malignant breast diseases demonstrating molecular profiles similar to those of breast cancer patients were enrolled into this follow-up study. In the interviews, for patients identified as predisposed to cancer, a specialised questionnaire has been set up to characterise individual risk factors and estimate their potential impacts on cancer onset and progression. RESULTS AND CONCLUSIONS: By utilising the technological tool of diagnostic windows, 13 individuals have been identified demonstrating molecular profiles typical for patients diagnosed with breast cancer. The current paper summarises the analytical results and makes statements to the application of the pathology-specific molecular profiles recognised as the technological tool for improved diagnostic approach, breast cancer risk assessment and preventive health care management. The necessity to create individual patient profiles and analyse the evolution of the molecular signature is justified for advanced medical services. Expert recommendations are provided to promote further developments in the field of advanced breast cancer management. PMID- 24228817 TI - Experiences of possession and paranormal phenomena among women in the general population: are they related to traumatic stress and dissociation? AB - This study sought to determine the prevalence of experiences of possession and paranormal phenomena (PNP) in the general population and their possible relations to each other and to traumatic stress and dissociation. The study was conducted on a representative female sample recruited from a town in central eastern Turkey. The Dissociative Disorders Interview Schedule, the posttraumatic stress disorder (PTSD) and borderline personality disorder sections of the Structured Clinical Interviews for DSM-IV Axis-I and Personality Disorders, and the Childhood Abuse and Neglect Questionnaire were administered to 628 women. Of these, 127 (20.2%) women reported at least 1 type of PNP and 13 (2.1%) women reported possession. Women with a dissociative disorder reported all types of possession and PNP (except telepathy) more frequently than those without. Whereas women with a trauma history in childhood and adulthood or PTSD reported possession more frequently than those without, PNP were associated with childhood trauma only. Factor analysis yielded 4 dimensions: possession by and/or contact with nonhuman entities, extrasensory communications, possession by a human entity, and precognition. These factors correlated with number of secondary features of dissociative identity disorder and Schneiderian symptoms. Latent class analysis identified 3 groups. The most traumatized group, with predominantly dissociative and trauma-related disorders, had the highest scores on all factors. Notwithstanding their presence in healthy individuals, possession and PNP were associated with trauma and dissociation in a subgroup of affected participants. Both types of experience seem to be normal human capacities of experiencing that may be involved in response to traumatic stress. Given the small numbers, this study should be considered preliminary. PMID- 24228818 TI - Enzymatic properties of Thermoanaerobacterium thermosaccharolyticum beta glucosidase fused to Clostridium cellulovorans cellulose binding domain and its application in hydrolysis of microcrystalline cellulose. AB - BACKGROUND: The complete degradation of the cellulose requires the synergistic action of endo-beta-glucanase, exo-beta-glucanase, and beta-glucosidase. But endo beta-glucanase and exo-beta-glucanase can be recovered by solid-liquid separation in cellulose hydrolysis by their cellulose binding domain (CBD), however, the beta-glucosidases cannot be recovered because of most beta-glucosidases without the CBD, so additional beta-glucosidases are necessary for the next cellulose degradation. This will increase the cost of cellulose degradation. RESULTS: The glucose-tolerant beta-glucosidase (BGL) from Thermoanaerobacterium thermosaccharolyticum DSM 571 was fused with cellulose binding domain (CBD) of Clostridium cellulovorans cellulosome anchoring protein by a peptide linker. The fusion enzyme (BGL-CBD) gene was overexpressed in Escherichia coli with the maximum beta-glucosidase activity of 17 U/mL. Recombinant BGL-CBD was purified by heat treatment and following by Ni-NTA affinity. The enzymatic characteristics of the BGL-CBD showed optimal activities at pH 6.0 and 65 degrees C. The fusion of CBD structure enhanced the hydrolytic efficiency of the BGL-CBD against cellobiose, which displayed a 6-fold increase in Vmax/Km in comparison with the BGL. A gram of cellulose was found to absorb 643 U of the fusion enzyme (BGL-CBD) in pH 6.0 at 50 degrees C for 25 min with a high immobilization efficiency of 90%. Using the BGL-CBD as the catalyst, the yield of glucose reached a maximum of 90% from 100 g/L cellobiose and the BGL-CBD could retain over 85% activity after five batches with the yield of glucose all above 70%. The performance of the BGL CBD on microcrystalline cellulose was also studied. The yield of the glucose was increased from 47% to 58% by adding the BGL-CBD to the cellulase, instead of adding the Novozyme 188. CONCLUSIONS: The hydrolytic activity of BGL-CBD is greater than that of the Novozyme 188 in cellulose degradation. The article provides a prospect to decrease significantly the operational cost of the hydrolysis process. PMID- 24228820 TI - Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma. AB - We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement. PMID- 24228819 TI - The role of arginine and arginine-metabolizing enzymes during Giardia - host cell interactions in vitro. AB - BACKGROUND: Arginine is a conditionally essential amino acid important in growing individuals and under non-homeostatic conditions/disease. Many pathogens interfere with arginine-utilization in host cells, especially nitric oxide (NO) production, by changing the expression of host enzymes involved in arginine metabolism. Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite Giardia intestinalis to investigate the role of arginine and arginine-metabolizing enzymes during intestinal protozoan infections. RESULTS: RNA expression analyses of major arginine metabolizing enzymes revealed the arginine-utilizing pathways in human IECs (differentiated Caco-2 cells) grown in vitro. Most genes were constant or down regulated (e.g. arginase 1 and 2) upon interaction with Giardia, whereas inducible NO synthase (iNOS) and ornithine decarboxylase (ODC) were up-regulated within 6 h of infection. Giardia was shown to suppress cytokine-induced iNOS expression, thus the parasite has both iNOS inducing and suppressive activities. Giardial arginine consumption suppresses NO production and the NO-degrading parasite protein flavohemoglobin is up-regulated in response to host NO. In addition, the secreted, arginine-consuming giardial enzyme arginine deiminase (GiADI) actively reduces T-cell proliferation in vitro. Interestingly, the effects on NO production and T cell proliferation could be reversed by addition of external arginine or citrulline. CONCLUSIONS: Giardia affects the host's arginine metabolism on many different levels. Many of the effects can be reversed by addition of arginine or citrulline, which could be a beneficial supplement in oral rehydration therapy. PMID- 24228821 TI - Cost-effectiveness analysis of varicella vaccine as post-exposure prophylaxis in Hong Kong. AB - OBJECTIVES: The varicella vaccine is an effective post-exposure prophylaxis (PEP) for chickenpox. This study aimed to analyze the cost-effectiveness of PEP using varicella vaccine for pediatric patients from the perspective of the public healthcare provider in Hong Kong. METHODS: A decision tree was designed to compare cost and clinical outcomes of PEP with varicella vaccine versus no PEP in pediatric patients (aged 1-18 y) susceptible to chickenpox with household exposure. Two tiers of outcome were simulated: (1) total direct medical cost per subject exposed, and (2) the quality-adjusted life-year (QALY) loss associated with chickenpox per subject exposed. Model inputs were retrieved from local epidemiology and the medical literature. A sensitivity analysis was performed on all parameters to test the robustness of model results. RESULTS: The base-case analysis showed PEP with varicella vaccine to be less costly (expected cost USD 320 vs USD 731) with lower QALY loss (0.00423 QALY vs 0.01122 QALY) when compared to no PEP. The sensitivity analysis showed that PEP with varicella vaccine was less costly if PEP effectiveness was > 6.2% or the chickenpox infection rate without PEP was > 8.6%. In 10,000 Monte Carlo simulations, PEP with vaccine was cost-effective over 99% of the time, with a mean cost saving of USD 611 per patient (95% confidence interval USD 602-620; p < 0.001) and lower mean QALY loss of 0.00809 QALY (95% confidence interval 0.00802-0.00816 QALY; p < 0.001). CONCLUSIONS: Using varicella vaccine as PEP appears to be a cost-saving strategy to avert QALY loss in susceptible pediatric patients exposed to chickenpox in Hong Kong. PMID- 24228822 TI - Liver abscess due to Klebsiella pneumoniae: risk factors for metastatic infection. AB - INTRODUCTION: Klebsiella pneumoniae-associated liver abscess (KPLA) is often accompanied by extrahepatic complications. We investigated the clinical features and outcomes of patients with and without metastatic infections and compared the 2 groups. METHODS: We retrospectively reviewed the medical records of 161 patients with KPLA who were admitted to 2 tertiary referral hospitals in Korea. RESULTS: In total, 9.9% had a metastatic infection. The most commonly involved distant sites were the eyes (n = 7) and the lungs (n = 6). In multivariate analysis, diabetes mellitus as an underlying disease (odds ratio (OR) 2.30, 95% confidence interval (CI) 1.05-9.51; p = 0.03) and a platelet count < 80,000/mm(3) (OR 11.60, 95% CI 2.53-53.26; p = 0.002) were associated with metastatic infection. Extended-spectrum beta-lactamase (ESBL) production was not observed in K. pneumoniae from patients with metastatic infection, whereas 3.4% of the bacteria in patients without metastatic infection had ESBL production. However, this difference was not statistically significant (p = 0.45). The in-hospital mortality rate was not significantly different (0% vs. 2.8%; p = 0.52). By multivariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was independently associated with mortality among patients with KPLA (OR 1.5, 95% CI 1.12-2.00; p = 0.006). CONCLUSIONS: Clinicians must be aware of potential metastatic infections in patients with KPLA, especially if they have diabetes mellitus and thrombocytopenia. The APACHE II score was predictive of mortality in patients with KPLA. PMID- 24228823 TI - Changes in acute mastoiditis in a single pediatric tertiary medical center: our experience during 2008-2009 compared with data for 1983-2007. AB - OBJECTIVE: The objective of this study was to assess clinical reports and bacteriological changes over a 25-y period in children with acute mastoiditis. METHODS: The medical files of all children with a discharge diagnosis of mastoiditis, hospitalized in a tertiary pediatric medical center over a 2-y period (2008-2009), were reviewed and compared to previously published data from the same center for the y 1983-1985, 1993-1995, and 2003-2007. RESULTS: One hundred and thirty-four children (143 episodes) with acute mastoiditis were identified during 2008-2009; 81% had fever, 95% auricular displacement, and 80% post-auricular swelling. Forty-nine children were diagnosed with acute otitis media and had been treated with antibiotics prior to hospitalization. However, 22% showed no clinical symptoms preceding ear protrusion. Cultures grew Streptococcus pneumoniae in 32%, Streptococcus pyogenes in 20%, Pseudomonas aeruginosa in 13%, and Haemophilus influenzae in 10% of cases. From 1990 to 2005, the incidence of S. pyogenes isolation increased from approximately 5% to 20%. During this period, the number of cases increased from 8-20 to 67 per y. CONCLUSIONS: S. pyogenes has emerged as a significant pathogen. We found that acute mastoiditis may appear without preceding symptoms in approximately 22% of cases. PMID- 24228825 TI - Cellulomonas, an emerging pathogen: a case report and review of the literature. AB - Cellulomonas is a rare but emerging human pathogen, causing infection in only 4 reported cases in the literature. We present the first case of ascending cholangitis with Cellulomonas bacteremia and sepsis, as well as a brief review of the literature. We summarize every case of Cellulomonas reported in the medical literature, including treatments and outcomes. PMID- 24228824 TI - Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection in Seoul, South Korea. AB - BACKGROUND: There have been various efforts to identify less costly but still accurate methods for monitoring the response to HIV treatment. We evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Seoul, South Korea. METHODS: We conducted the first prospective study of pooled nucleic acid testing (NAT) using a 5 minipool + algorithm strategy versus individual viral load testing for patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. The viral load assay used has a lower level of detection of 20 HIV RNA copies/ml, and the cost per assay is US$ 136. The 5 minipool +algorithm strategy was applied and 43 pooled samples were evaluated. The relative efficiency and accuracy of the pooled NAT were compared with those of individual testing. RESULTS: Using the individual viral load assay, 15 of 215 (7%) plasma samples had more than 200 HIV RNA copies/ml. The pooled NAT using the 5 minipool + algorithm strategy was applied to 43 pooled samples; 111 tests were needed to test all samples when virologic failure was defined at HIV RNA >= 200 copies/ml. Therefore, 104 tests were saved over individual testing, with a relative efficiency of 0.48. When evaluating costs, a total of US$ 14,144 was saved for 215 individual samples during 10 months. The negative predictive value was 99.5% for all samples with HIV RNA >= 200 copies/ml. CONCLUSIONS: The pooled NAT with 5 minipool + algorithm strategy seems to be a very promising approach to effectively monitor patients receiving ART and to save resources. PMID- 24228826 TI - Herpes simplex virus encephalitis during treatment with etanercept. AB - Tumor necrosis factor alpha (TNF-alpha) inhibitors are widely used for the treatment of various inflammatory conditions. They are associated with an increased risk for infections. We report a case of herpes simplex virus type 1 (HSV-1) encephalitis in a patient receiving etanercept and review the literature on TNF-alpha and TNF-alpha inhibitors, and their importance in the pathophysiology of herpes simplex encephalitis. PMID- 24228827 TI - Empirical impact evaluation of the WHO Global Code of Practice on the International Recruitment of Health Personnel in Australia, Canada, UK and USA. AB - BACKGROUND: The active recruitment of health workers from developing countries to developed countries has become a major threat to global health. In an effort to manage this migration, the 63rd World Health Assembly adopted the World Health Organization (WHO) Global Code of Practice on the International Recruitment of Health Personnel in May 2010. While the Code has been lauded as the first globally-applicable regulatory framework for health worker recruitment, its impact has yet to be evaluated. We offer the first empirical evaluation of the Code's impact on national and sub-national actors in Australia, Canada, United Kingdom and United States of America, which are the English-speaking developed countries with the greatest number of migrant health workers. METHODS: 42 key informants from across government, civil society and private sectors were surveyed to measure their awareness of the Code, knowledge of specific changes resulting from it, overall opinion on the effectiveness of non-binding codes, and suggestions to improve this Code's implementation. RESULTS: 60% of respondents believed their colleagues were not aware of the Code, and 93% reported that no specific changes had been observed in their work as a result of the Code. 86% reported that the Code has not had any meaningful impact on policies, practices or regulations in their countries. CONCLUSIONS: This suggests a gap between awareness of the Code among stakeholders at global forums and the awareness and behaviour of national and sub-national actors. Advocacy and technical guidance for implementing the Code are needed to improve its impact on national decision makers. PMID- 24228828 TI - Transient kinetics and rate-limiting steps for the processive cellobiohydrolase Cel7A: effects of substrate structure and carbohydrate binding domain. AB - Cellobiohydrolases are exoacting, processive enzymes that effectively hydrolyze crystalline cellulose. They have attracted considerable interest because of their role in both natural carbon cycling and industrial enzyme cocktails used for the deconstruction of cellulosic biomass, but many mechanistic and regulatory aspects of their heterogeneous catalysis remain poorly understood. Here, we address this by applying a deterministic model to real-time kinetic data with high temporal resolution. We used two variants of the cellobiohydrolase Cel7A from Hypocrea jecorina , and three types of cellulose as substrate. Analysis of the pre-steady state regime allowed delineation rate constants for both fast and slow steps in the enzymatic cycle and assessment of how these constants influenced the rate of hydrolysis at quasi-steady state. Processive movement on the cellulose strand advanced with characteristic times of 0.15-0.7 s per step at 25 degrees C, and the rate was highest on amorphous substrate. The cellulose binding module was found to raise this rate on crystalline, but not on amorphous, substrate. The rapid processive movement signified high intrinsic reactivity, but this parameter had marginal influence on the steady-state rate. This was because dissociation and association were slower and, hence, rate limiting. Specifically, the dissociation from the strand was found to occur with characteristic times of 45 100 s. This meant that dissociation was the bottleneck, except at very low substrate loads (0.5-1 g/L), where association became slower. PMID- 24228829 TI - Prognostic factors and health-related quality of life in ocular Myasthenia Gravis (OMG). AB - We evaluate the factors predictive of prognosis in 91 Caucasian patients affected by ocular myasthenia gravis (OMG), followed at our Institution during an observational time, ranging from 12 to 240 months. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was used to grade the disease severity. We considered as outcome measures the variation in two subscores, ocular (O-QMG) and nonocular (NO-QMG); the last one reflected bulbar, neck, extremity functions. None of the independent variables evaluated for association with the outcome, as age of onset, type of therapy, length of interval between first and last examinations, and presence of antibodies to acetylcholine receptors (AChR-Abs) significantly affected the evolution of O-QMG and of NO-QMG. Health-related quality of life (HRQol) was assessed in 63 patients. Variations of diplopia or ptosis did not affect significantly physical (PCS) or mental composite subscores (MCS) of the Short-Form Health Survey (SF 36). Human leukocyte antigen (HLA) genotyping was studied to explore whether HLA class I and II allelic distribution differed among MG patients and controls. None of the studied HLA alleles significantly differed between OMG patients and controls. Similarly, none of the alleles with frequencies higher than 15% either in OMG patients or in controls was significantly associated, after Bonferroni correction, with the presence or absence of anti-AChR-Abs in serum. PMID- 24228830 TI - Characteristics of multiple sclerosis in the Middle East with special reference to the applicability of international guidelines to the region. AB - We have reviewed the clinical literature with reference to the local applicability of guidelines for the diagnosis and management of multiple sclerosis (MS) in the Middle East. There is a substantial burden of MS in the region: the prevalence of the disease appears to have increased markedly in recent decades, with a faster rate of increase in female vs. male patients. The aetiology and presentation of MS appears to be broadly similar in the Middle East to that in other regions. Interferon-beta is the most commonly used treatment for MS in the Middle East, as elsewhere, although it is unclear to what extent economic constraints act as a barrier to accessing this treatment. Similarly, limited available data suggest that the availability of MRI scanners appears to be lower in the Middle East than in more developed nations. Little is known concerning other potential barriers to treatment. There is a need for further research on aspects of management of MS beyond the pharmacological aspects of treatment to assess fully the potential barriers to the adoption of international guidelines for the diagnosis and management of the disease in the Middle East. PMID- 24228831 TI - Effect of hyperbaric oxygen therapy on cerebral vasospasm: a vascular morphometric study in an experimental subarachnoid hemorrhage model. AB - This study was undertaken to investigate the preventive or therapeutic effect of hyperbaric oxygen therapy (HBOT) on cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). Twenty rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH or sham operation (control group, n = 5). Animals in Group II were subjected to sham operation and received no treatment after the procedure (sham group, n = 5). Animals in Group III were subjected to SAH and received no treatment after SAH induction (SAH group, n = 5). Animals in Group IV were subjected to SAH and received five sessions of HBOT at 2.4 atmospheres absolute (ATA) for 2 h (treatment group, n = 5). Animals were euthanized by perfusion and fixation 72 h after procedures. Basilar artery vasospasm indices, arterial wall thicknesses, and cross-sectional luminal areas were evaluated. Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Mean basilar artery vasospasm index in the treatment group was significantly smaller than in the SAH group. Mean basilar artery wall thickness in the treatment group was significantly smaller than in the SAH group. Mean basilar artery cross-sectional luminal area in the treatment group showed an increase relative to the SAH group, but this difference remained statistically insignificant. Our results demonstrated that repeated application of HBOT at 2.4 ATA for 2 h attenuated vasospastic changes such as increased vasospasm index and arterial wall thickness. HBOT is thus a promising candidate for SAH-induced vasospasm. Further studies are needed to evaluate maximal effect and optimal application regimen. PMID- 24228832 TI - Magnesium deficit ? overlooked cause of low vitamin D status? AB - Like vitamin D deficit, magnesium deficit is considered to be a risk factor for cardiovascular disease. Several steps in the vitamin D metabolism, such as vitamin D binding to its transport protein and the conversion of vitamin D into the hormonal form 1,25-dihydroxyvitamin D by hepatic and renal hydroxylation, depend on magnesium as a cofactor. A new analysis of two National Health and Nutrition Examination Surveys data sets, published in BMC Medicine, investigated potential interactions between magnesium intake, circulating 25-hydroxyvitamin D, which is the generally accepted indicator of vitamin D status, and mortality. Data indicate a reduced risk of insufficient/deficient vitamin D status at high magnesium intake and an inverse association between circulating 25-hydroxyvitamin D and mortality, particularly cardiovascular mortality, among those with magnesium intake above the median. The study provides important findings concerning potential metabolic interactions between magnesium and vitamin D and its clinical relevance. However, results should be considered preliminary since biochemical data on individual magnesium status were lacking, confounding cannot be excluded and questions on the dose?response relationship still remain to be answered. Please see related research article: http://www.biomedcentral.com/1741 7015/11/187. PMID- 24228833 TI - Social media and health. PMID- 24228834 TI - Mortality toll due to avoiding estrogen therapy in hysterectomized women: estimates for 2002 - 2011. PMID- 24228835 TI - Determinants of the administration of continuous palliative sedation: a systematic review. AB - BACKGROUND: Little is known about the determining factors related to the administration of continuous palliative sedation. Knowledge of these determinants may assist physicians in identifying patients who are at high risk of developing refractory symptoms, enable physicians to inform patients, and optimize close monitoring. OBJECTIVE: The aim of this systematic review was to identify determinants of the administration of continuous palliative sedation. DESIGN: A systematic review of PubMed, EMBASE, and CINAHL was performed to identify English, Dutch, and German language papers published from January 1990 through April 2011. Inclusion was based on the following criteria: patient-based research on continuous palliative sedation, studies investigating determinants of palliative sedation and/or comparison between sedated and nonsedated cohorts, and studies using multivariate analyses and of fair to good or good methodological quality. RESULTS: In total, eight papers were reviewed. The following nine factors were found to be associated with the administration of continuous palliative sedation: younger age, male sex, having cancer, feelings of hopelessness, dying in a hospital, living in a Dutch speaking community setting, very nonreligious or extremely nonreligious physicians, physicians working in "other hospital" specialties, and physicians in favor of assisted death. CONCLUSIONS: Given the variation in study designs and the limitations of the included studies, the outcomes should be interpreted carefully. Further research is needed, particularly regarding factors that can be influenced and that may alter the course of a patient's symptoms and the patient's eventual need for palliative sedation. PMID- 24228837 TI - Estimated daily intake and hazard quotients and indices of phthtalate diesters for young danish men. AB - Because of wide exposure to phthalates, we investigated whether simultaneous exposure to several phthalates reached levels that might cause adverse antiandrogenic effects. Thirty three healthy young Danish men each delivered three 24-h urine samples during a three months period. The daily intakes of the sum of di-n-butyl and di-iso-butyl phthalate, di(2-ethylhexyl) phthalate, di-iso nonyl phthalate, and butylbenzyl phthalate were estimated based on urinary excretion of the metabolites. Based on a hazard quotient (HQ) of the individual phthalate (i.e., the ratio between the daily intake and an acceptable level of exposure), a hazard index (HI) for each man was calculated as the sum of HQs for the individual phthalates. All men were exposed to all phthalates during the urine collection periods. Median HIs were all below 1 (i.e., below an acceptable cumulative threshold) ranging from 0.11 to 0.17 over the three different sample collections. Of the 33 men, 2 men had HIs above 1 in one of their three samples, indicating that occasionally the combined exposure to the investigated phthalates reached a level that may not be considered safe. Besides the phthalates investigated here, humans are exposed to numerous other chemicals that also may contribute to a cumulative antiandrogenic exposure. PMID- 24228838 TI - Enantiopure cis-2,5-disubstituted 2,5-dihydropyrroles from D-glycal-derived vinyl aziridines. AB - Upon treatment with the K- and Li-enolates of a methylene active compound, such as dimethyl malonate and dibenzoylmethane, D-allal- and D-galactal-derived vinyl N-mesyl aziridines are stereoselectively transformed, in a unique step, into diastereoisomeric, highly functionalized, enantiopure cis-2,5-disubstituted N mesyl-2,5-dihydropyrroles. PMID- 24228839 TI - Multianalyte microphysiometry reveals changes in cellular bioenergetics upon exposure to fluorescent dyes. AB - Fluorescent dyes have been designed for internal cellular component specificity and have been used extensively in the scientific community as a means to monitor cell growth, location, morphology, and viability. However, it is possible that the introduction of these dyes influences the basal function of the cell and, in turn, the results of these studies. Electrochemistry provides a noninvasive method for probing the unintended cellular affects of these dyes. The multianalyte microphysiometer (MAMP) is capable of simultaneous electrochemical measurement of extracellular metabolites in real-time. In this study, analytes central to cellular metabolism, glucose, lactate, oxygen, as well as extracellular acidification were monitored to determine the immediate metabolic effects of nuclear stains, including SYTO, DAPI dilactate, Hoechst 33342, and FITC dyes upon the pheochromocytoma PC-12 cells and RAW 264.7 macrophages. The experimental results revealed that the SYTO dye 13 significantly decreased glucose and oxygen consumption and increased extracellular acidification and lactate production in both cell lines, indicating a shift to anaerobic respiration. No other dyes caused significantly definitive changes in cellular metabolism upon exposure. This study shows that fluorescent dyes can have unintended effects on cellular metabolism and care should be taken when using these probes to investigate cellular function and morphology. PMID- 24228840 TI - Is fluorine-18 fluorodeoxyglucose positron emission tomography useful for the thyroid nodules with indeterminate fine needle aspiration biopsy? A meta-analysis of the literature. AB - BACKGROUND: The indeterminate fine needle aspiration biopsy (FNAB) results present a clinical dilemma for physicians. The aim of this study was to evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the detection of these indeterminate lesions. METHODS: Seven studies (involving a total of 267 patients) published before November 2012 were reviewed. Systematic methods were used to identify, select, and evaluate the methodological quality of the studies as well as to summarize the overall findings of sensitivity and specificity. RESULTS: A total number of 70 patients were confirmed to have malignant lesions, with a cancer prevalence of 26.2% (70/267; ranging from 19.6% to 40.0% in these studies). The pooled sensitivity and specificity of PET or PET/CT for the detection of cancer was 89.0% (95% CI: 79.0% ~ 95.0%) and 55.0% (95% CI: 48.0% ~ 62.0%), respectively. There was no evidence of threshold effects or publication bias. The area [+/ standard error (+/-SE)] under the symmetrical sROC curve was 0.7207 +/- 0.1041. Although SUVmax was higher in malignant lesions (P < 0.01), there was still a great overlap. The best cut-off value of SUVmax for differentiation was 2.05; but with a high sensitivity of 89.8% and low specificity of 42.0%. CONCLUSION: F-FDG PET or PET/CT showed a high sensitivity in detecting thyroid cancers in patients with indeterminate FNAB results. Further examination was strongly recommended when an FDG-avid lesion was detected. PMID- 24228842 TI - "Criss-crossed" dinucleating behavior of an N4 Schiff base ligand: formation of a MU-OH,MU-O2 dicobalt(III) core via O2 activation. AB - We report the synthesis and structural characterization of a dicobalt(III) complex with a MU-OH,MU-O2 core, namely MU-OH,MU-O2-[Co(enN4)]2(X)3 [1(ClO4)3 and 1(BF4)3]. The dinuclear core is cross-linked by two N4 Schiff base ligands that span each cobalt center. The formally Co(III)-Co(III) dimer is formed spontaneously upon exposure of the mononuclear Co(II) complex to air and exhibits a nu(O-O) value at 882 cm(-1) that shifts to 833 cm(-1) upon substitution with (18)O2. The CV of 1(BF4)3 exhibits a reversible {Co(III)-Co(III)}<->{Co(III) Co(IV)} redox process, and we have investigated the oxidized {Co(III)-Co(IV)} species by EPR spectroscopy (g = 2.02, 2.06; S = 1/2 signal) and DFT calculations. PMID- 24228841 TI - The treatment of vasomotor rhinitis with intranasal corticosteroids. AB - OBJECTIVE: Intranasal steroids (INS) are firmly established as the therapy for choice for allergic rhinitis, but their role in vasomotor rhinitis (VMR) is not fully characterized. This review examines the potential mechanisms of action and reported efficacy of INS in patients with VMR. RESULTS: INS, through intracellular activation of the glucocorticoid receptor, down-regulate the recruitment and activation of inflammatory cells (T-lymphocytes, eosinophils, mast cells, basophils, neutrophils, macrophages), increase degradation of neuropeptides, and reduce epithelial cell activity, vascular permeability, and chemokine secretion. It is likely that more than vasoconstriction is responsible for the clinical effects of INS.Eight INS can be prescribed for rhinitis in the US; only 4 have been studied for VMR. Seventy-four percent of patients treated with beclomethasone dipropionate considered themselves symptom-free or greatly improved versus 31% with placebo. Budesonide significantly reduced rhinitis symptoms and methacholine-induced nasal secretions compared with placebo. Fluticasone propionate compared with placebo provided significantly greater relief from nasal obstruction; computed tomographic scans showed significant reductions in the mucosal area of the lower turbinates. Mometasone furoate produced numerically better rhinitis symptom scores and, when discontinued, lower relapse rates than placebo. CONCLUSION: Data supports INS as beneficial pharmacotherapy for VMR. PMID- 24228843 TI - Acute peritraumatic dissociation: in favor of a phenomenological inquiry. AB - Fundamental aspects of trauma--among them dissociation during trauma, which is considered one of the strongest predictors of posttraumatic stress disorder-are not fully understood. This article argues that the application of the phenomenological structure of time and the phenomenological description of the self (minimal self, sense of ownership, sense of agency, sense of self) to dissociation during trauma can improve our understanding of this phenomenon-at its occurrence and during any possible ensuing symptoms. In addition, it is argued that the phenomenological approach, as a method that focuses on the bodily level of experience, in particular the body as it is experienced from within, enables us to penetrate the traumatic experience. Thus, by applying the phenomenological approach we may be able to improve our understanding of the traumatic experience and enable the development of better treatment. PMID- 24228844 TI - Cost of behavior change communication channels of Manoshi -a maternal, neonatal and child health (MNCH) program in urban slums of Dhaka, Bangladesh. AB - BACKGROUND: The cost of behavior change communication (BCC) interventions has not been rigorously studied in Bangladesh. This study was conducted to assess the implementation costs of a BCC intervention in a maternal, neonatal and child health program (Manoshi) run by BRAC, which has been operating in the urban slums of Dhaka since 2007. The study estimates the costs of BCC tools per exposure among the different types of BCC channels: face-to-face, group counseling, and mass media. METHODS: The study was conducted from November 2010 to April 2011 in the Dhaka urban slum area. A micro-costing approach was applied using primary and secondary data sources to estimate the cost of BCC tools. Primary data were collected through interviews with service-providers and managers from the Manoshi program, observations of group counseling, and mass media events. RESULTS: Per exposure, the cost of face-to-face counseling was found to be 3.08 BDT during pregnancy detection, 3.11 BDT during pregnancy confirmation, 12.42 BDT during antenatal care, 18.96 BDT during delivery care and 22.65 BDT during post-natal care. The cost per exposure of group counseling was 22.71 BDT (95% CI 21.30 24.87) for Expected Date of Delivery (EDD) meetings, 14.25 BDT (95% CI 12.37 16.12) for Women Support Group meetings, 17.83 BDT (95% CI 14.90-20.77) for MNCH committee meetings and 6.62 BDT (95% CI 5.99-7.26) for spouse forum meetings. We found the cost per exposure for mass media interventions was 9.54 BDT (95% CI 7.30-12.53) for folk songs, 26.39 BDT (95% CI 23.26-32.56) for street dramas, 0.39 BDT for TV-broadcasting and 7.87 BDT for billboards. Considering all components reaching the target audience under each broader type of channel, the total cost per exposure was found to be 60.22 BDT (0.82 USD) for face-to-face counseling, 61.40 BDT (0.82 USD) for group counseling and 44.19 BDT (0.61 USD) for mass media. CONCLUSIONS: The total cost for group counseling was the highest per exposure, followed by face-to-face counseling and mass media. The cost per exposure varied substantially across BCC channels due to differences in cost drivers such as personnel, materials and refreshments. The cost per exposure can be valuable for planning and resource allocation related to the implementation of BCC interventions in low resource settings. PMID- 24228845 TI - Risk factors for Coxiella burnetii antibodies in bulk tank milk from Danish dairy herds. AB - The aim was to identify risk factors associated with Coxiella burnetii antibody positivity in bulk tank milk (BTM) samples from 100 randomly selected Danish dairy cattle herds. Antibody levels were measured by an enzyme-linked immuno sorbent assay. Before testing the herds, the farm managers were interviewed about hired labour, biosecurity, housing and herd health during the 12 months prior to the study. Variables considered important for C. burnetii antibody positivity in multivariable logistic regression analysis included the sharing of machines between farms (OR = 3.6), human contacts (OR = 4.2), artificial insemination by other people than artificial insemination technicians (OR = 7.7), routine herd health contract with the veterinarian (OR = 4.3) and hygiene precautions taken by veterinarians (OR = 5). In addition, herd size, hired labour, trading of cattle between farms, quarantine and use of calving and disease pens also showed significant association in univariable analysis. This study demonstrates that strict biosecurity is important for the prevention of infections with C. burnetii. PMID- 24228848 TI - Use of creatine kinase to induce multistep reactions in infrared spectroscopic experiments. AB - An extension of current approaches to trigger enzymatic reactions in reaction induced infrared difference spectroscopy experiments is described. A common procedure is to add a compound that induces a reaction in the protein of interest. To be able to induce multistep reactions, we explored here the use of creatine kinase (CK) for the study of phosphate transfer mechanisms. The enzymatic reaction of CK could be followed using bands at 1614 and 979 cm(-1) for creatine phosphate consumption, at 944 cm(-1) for ADP consumption, and at 1243, 992, and 917 cm(-1) for ATP formation. The potential of CK to induce multistep reactions in infrared spectroscopic experiments was demonstrated using the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1a) as the protein of interest. ADP binding to the ATPase was triggered by photolytic release of ADP from P(3)-1-(2 nitro)phenylethyl ADP (caged ADP). CK added in small amounts converted the released ADP to ATP on the time scale of minutes. This phosphorylated the ATPase and led to the formation of the first phosphoenzyme intermediate Ca2E1P. Thus a difference spectrum could be obtained that reflected the reaction from the ADP ATPase complex to the first phosphoenzyme intermediate. Comparison with a phosphorylation spectrum obtained when the initial state was the ATP ATPase complex revealed the contribution of ATP's gamma-phosphate to the conformational change of the ATPase upon nucleotide binding: gamma-phosphate binding modifies the structure of a beta-sheet, likely in the phosphorylation domain, and shifts its spectral position from ~1640 to ~1630 cm(-1). Upon phosphorylation of the ATPase, the beta-sheet relaxes back to a structure that is intermediate between that adopted in the ADP bound state and that in the ATP bound state. PMID- 24228847 TI - Cross-over study of influence of oral vitamin C supplementation on inflammatory status in maintenance hemodialysis patients. AB - BACKGROUND: Both vitamin C deficiency and inflammation are prevalent in maintenance hemodialysis (MHD) patients. In this study, we aimed to elucidate the effect of oral vitamin C supplementation on inflammatory status in MHD patients with low vitamin C level and high hypersensitive C-reactive protein (hs-CRP) level. METHODS: A total of 128 patients were recruited in our present study. Patients were divided into two groups. In group 1 (n = 67), patients were orally administered with 200 mg/day vitamin C in the first 3 months, and then the vitamin C supplementation was withdrawn in the next 3 months. In group 2 (n = 61), patients were not given vitamin C in the first 3 months, and then they were orally administered with 200 mg/day in the next 3 months. Levels of hs-CRP, prealbumin, albumin and hemoglobin as well as the EPO resistance index (ERI) were determined at the baseline and every 3 months throughout the study. Plasma vitamin C level was determined by high-performance liquid chromatography with UV detection. RESULTS: Among the 128 patients, 28 of them dropped out of the study before completion. Consequently, a total of 100 patients (group 1: n = 48; group 2: n = 52) were included in the final analysis. At the baseline, the plasma vitamin C level of all patients was less than 4 MUg/mL. However, this proportion was decreased to 20% after the vitamin C supplementation for 3 months. Compared with patients without the vitamin C supplementation, a decreased level of hs-CRP and an increased level of prealbumin were induced by the vitamin C supplementation for 3 months in both groups. However, levels of these biomarkers returned to their original state after the supplementation was withdrawn. Same beneficial effects on plasma albumin, hemoglobin and ERI response to vitamin C supplementation were observed in the two groups without statistical significance. CONCLUSIONS: The inflammatory status in MHD patients with plasma vitamin C deficiency and high levels of inflammatory markers could be partially improved by long-term oral administration of small doses of vitamin C. TRIAL REGISTRATION: The clinical trial number: NCT01356433. PMID- 24228846 TI - Spatial distribution of G6PD deficiency variants across malaria-endemic regions. AB - BACKGROUND: Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine's widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants. METHODS: A literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening. RESULTS: Variants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A(-202A) mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated. CONCLUSIONS: G6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies. The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes. PMID- 24228849 TI - Quasiperiodic moire plasmonic crystals. AB - This paper describes the properties of silver plasmonic crystals with quasiperiodic rotational symmetries. Compared to periodic plasmonic crystals, quasiperiodic moire structures exhibited an increased number of surface plasmon polariton modes, especially at high angles of excitation. In addition, plasmonic band gaps were often formed at the intersections of these new modes. To identify the origin and predict the location of the band gaps, we developed a Bragg-based indexing system using the reciprocal lattice vectors of the moire plasmonic crystals. We showed that even more complicated quasiperiodic geometries could also be described by this indexing model. We anticipate that these quasiperiodic lattices will be useful for applications that require the concentration and manipulation of light over a broadband spectrum. PMID- 24228850 TI - Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans. AB - BACKGROUND: Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity. RESULTS: Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse. CONCLUSIONS: Mixed species biofilms are enhanced and associated with increased S. epidermidis specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S. epidermidis and C. albicans. PMID- 24228851 TI - Large-scale cell production of stem cells for clinical application using the automated cell processing machine. AB - BACKGROUND: Cell-based regeneration therapies have great potential for application in new areas in clinical medicine, although some obstacles still remain to be overcome for a wide range of clinical applications. One major impediment is the difficulty in large-scale production of cells of interest with reproducibility. Current protocols of cell therapy require a time-consuming and laborious manual process. To solve this problem, we focused on the robotics of an automated and high-throughput cell culture system. Automated robotic cultivation of stem or progenitor cells in clinical trials has not been reported till date. The system AutoCulture used in this study can automatically replace the culture medium, centrifuge cells, split cells, and take photographs for morphological assessment. We examined the feasibility of this system in a clinical setting. RESULTS: We observed similar characteristics by both the culture methods in terms of the growth rate, gene expression profile, cell surface profile by fluorescence activated cell sorting, surface glycan profile, and genomic DNA stability. These results indicate that AutoCulture is a feasible method for the cultivation of human cells for regenerative medicine. CONCLUSIONS: An automated cell-processing machine will play important roles in cell therapy and have widespread use from application in multicenter trials to provision of off-the-shelf cell products. PMID- 24228852 TI - Section 2. Exercise-Induced Bronchospasm: Albuterol versus Montelukast: Highlights of the Asthma Summit 2009: Beyond the Guidelines. AB - Exercise-induced bronchospasm (EIB) involves airway obstruction with an onset shortly after exercising. It can occur in individuals without a diagnosis of asthma, but is most common in asthmatic patients (and in this scenario may be referred to as exercise-induced asthma, EIA), correlating with the patient's degree of airway hyperreactivity. While albuterol is the most commonly used rescue and prophylactic medication for EIB, the leukotriene antagonist, monetlukast, may be an appropriate choice for some patients. Clinical data have shown that once-daily treatment with montelukast (5 or 10 mg tablet) can offer protection against EIB within 3 days for some patients. Such an approach might be preferred for patients who have difficulty with inhaled medications and for children who cannot access their inhalers during the school day. Montelukast also may be an option to reduce side effects associated with albuterol for individuals who exercise regularly. PMID- 24228853 TI - Role of vasoactive intestinal peptide in chronic obstructive pulmonary disease with pulmonary hypertension. AB - BACKGROUND: The aim of this study was to define the involvement of some biomarkers in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), with particular attention to sub-groups with a PH that is "out of proportion" (OP). MATERIALS AND METHODS: Patients with COPD without PH, with PH and marked airways obstruction, and with PH and mild airways obstruction were compared. Assays for human interleukin-6 (IL-6), leukotriene B4 (LTB4), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1) were performed on the blood samples taken during right heart catheterization (RHC) in a pulmonary artery. RESULTS: In all, 83 patients were enrolled and divided into three groups: 37 simple COPD (mean pulmonary artery pressure [mPAP] <25 mmHg) and 46 COPD with PH (mPAP >=25 mmHg). Among the latter, those who had a mPAP >=35 mmHg and forced expiratory volume in 1 sec [FEV1] >=50% were classified as OP (7 patients). Patients with PH were older and had a body mass index (BMI) higher than the other groups; moreover, they had lower FEV1 and carbon monoxide diffusion (DLCO) values. A lower level of partial pressure of oxygen in arterial blood (PaO2) was observed in the group of OP patients. The levels of ET-1, IL-6, and LTB4 were similar in each group; VIP was higher in the OP patients than in simple COPD and was related to PAP. CONCLUSIONS: In the patients with COPD and PH and in particular in the group of OP PH, VIP is significantly increased, probably to correct the imbalance between vasoconstrictor and vasodilatator mediators. PMID- 24228855 TI - Measuring the isoelectric point of the edges of clay mineral particles: the case of montmorillonite. AB - The isoelectric point (IEP) of the edge surface of a montmorillonite sample was determined by using electrophoretic mobility measurements. This parameter, which is fundamental for the understanding of the charging behavior of clay mineral surfaces, was never measured so far because of the presence of permanent negative charges within the montmorillonite structure, charges that mask the electrokinetic behavior of the edges. The strategy was to block or neutralize the structural charges with two different cations, methylene blue (MB(+)) and tetraethylenepentaminecopper(II) ([Cu(tetren)](2+)), so that the charging behavior of the particles becomes that of the edge surfaces. Adsorption isotherms of MB(+) and [Cu(tetren)](2+) at different ionic strengths (NaCl) were performed to establish the uptakes that neutralize the cation exchange capacity (CEC, 0.96 meq g(-1)) of the sample. At high adsorptive concentrations, there was a superequivalent adsorption of MB(+) (adsorption exceeding the CEC) and an equivalent adsorption of [Cu(tetren)](2+) (adsorption reaching the CEC). In both cases, structural charges were neutralized at uptakes very close to the CEC. Zeta potential (zeta) vs pH data at different ionic strengths of montmorillonite with adsorbed MB(+) allowed to estimate an upper limit of the edge's IEP, 5.3 +/- 0.2. The same kind of data obtained with adsorbed [Cu(tetren)](2+) provided a lower limit of the IEP, 4.0 +/- 0.2. These values are in agreement with previously informed IEP and point of zero charge of pyrophyllite, which is structurally analogous to montmorillonite but carries no permanent charges. The importance of knowing the IEP of the edge surface of clay minerals is discussed. This value characterizes the intrinsic reactivity of edges, that is, the protonating capacity of edge groups in absence of any electric field generated by structural charges. It also allows us to correct relative edge charge vs pH curves obtained by potentiometric titrations and to obtain the true edge charge vs pH curves at different electrolyte concentrations. PMID- 24228854 TI - Additional Saturday rehabilitation improves functional independence and quality of life and reduces length of stay: a randomized controlled trial. AB - BACKGROUND: Many inpatients receive little or no rehabilitation on weekends. Our aim was to determine what effect providing additional Saturday rehabilitation during inpatient rehabilitation had on functional independence, quality of life and length of stay compared to 5 days per week of rehabilitation. METHODS: This was a multicenter, single-blind (assessors) randomized controlled trial with concealed allocation and 12-month follow-up conducted in two publically funded metropolitan inpatient rehabilitation facilities in Melbourne, Australia. Patients were eligible if they were adults (aged >=18 years) admitted for rehabilitation for any orthopedic, neurological or other disabling conditions excluding those admitted for slow stream rehabilitation/geriatric evaluation and management. Participants were randomly allocated to usual care Monday to Friday rehabilitation (control) or to Monday to Saturday rehabilitation (intervention). The additional Saturday rehabilitation comprised physiotherapy and occupational therapy. The primary outcomes were functional independence (functional independence measure (FIM); measured on an 18 to 126 point scale), health-related quality of life (EQ-5D utility index; measured on a 0 to 1 scale, and EQ-5D visual analog scale; measured on a 0 to 100 scale), and patient length of stay. Outcome measures were assessed on admission, discharge (primary endpoint), and at 6 and 12 months post discharge. RESULTS: We randomly assigned 996 adults (mean (SD) age 74 (13) years) to Monday to Saturday rehabilitation (n = 496) or usual care Monday to Friday rehabilitation (n = 500). Relative to admission scores, intervention group participants had higher functional independence (mean difference (MD) 2.3, 95% confidence interval (CI) 0.5 to 4.1, P = 0.01) and health-related quality of life (MD 0.04, 95% CI 0.01 to 0.07, P = 0.009) on discharge and may have had a shorter length of stay by 2 days (95% CI 0 to 4, P = 0.1) when compared to control group participants. Intervention group participants were 17% more likely to have achieved a clinically significant change in functional independence of 22 FIM points or more (risk ratio (RR) 1.17, 95% CI 1.03 to 1.34) and 18% more likely to have achieved a clinically significant change in health-related quality of life (RR 1.18, 95% CI 1.04 to 1.34) on discharge compared to the control group. There was some maintenance of effect for functional independence and health-related quality of life at 6-month follow-up but not at 12-month follow-up. There was no difference in the number of adverse events between the groups (incidence rate ratio = 0.81, 95% CI 0.61 to 1.08). CONCLUSIONS: Providing an additional day of rehabilitation improved functional independence and health-related quality of life at discharge and may have reduced length of stay for patients receiving inpatient rehabilitation. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12609000973213 Please see related commentary: http://www.biomedcentral.com/10.1186/1741-7015-11-199. PMID- 24228856 TI - Consensus Description of Inclusion and Exclusion Criteria for Clinical Studies of Nonallergic Rhinopathy (NAR), Previously Referred to as Vasomotor Rhinitis (VMR), Nonallergic Rhinitis, and/or Idiopathic Rhinitis. AB - "Nonallergic rhinopathy" was defined by consensus at a Roundtable conference in December 2008 as "a chronic nasal condition with symptoms that may be perennial, persistent, intermittent or seasonal and/or elicited by recognized triggers." The definition includes a well-recognized set of clinical exposures that lead to the symptoms, predominantly congestion, rhinorrhea, and postnasal drip. These clinical characteristics help to identify patients for participation in clinical trials examining the efficacy of treatments for this important disease. The next step is to establish inclusion and exclusion criteria that will provide a framework for the clinical trials. Agreement on study criteria was obtained at the consensus conference by discussion, counterpoint, and compromise. PMID- 24228858 TI - One-pot synthesis of functionalized 2,5-dihydrofurans via an amine-promoted Petasis borono-Mannich reaction. AB - A series of functionalized 2,5-dihydrofurans were efficiently synthesized via an amine-promoted Petasis borono-Mannich reaction of 4-substituted 1,2-oxaborol 2(5H)-ols with salicylaldehydes in high yields. The process, which combines a boronic acid-based Mannich reaction and a highly efficient intramolecular SN2 cyclization, provides a one-step and efficient route toward 2,5-dihydrofurans from simple and stable starting materials. PMID- 24228859 TI - Streptozotocin-induced diabetes increases amyloid plaque deposition in AD transgenic mice through modulating AGEs/RAGE/NF-kappaB pathway. AB - BACKGROUND: An increasing number of studies have demonstrated of that diabetes mellitus (DM) is associated with an increased prevalence of Alzheimer disease (AD), the underlying mechanisms are still obscure. METHODS: We developed a streptozotocin (STZ)-induced diabetic AD transgenic mouse model and evaluated the effect of hyperglycemia on senile plaque formation. RESULTS: Our data showed that administration of STZ increased the level of blood glucose and increased the advanced glycation end products (AGEs) in brain tissue, and further enhanced the expression levels of the receptor for AGEs (RAGE) and the nuclear factor-kappa B (NF-kappaB) in the brain, and accelerated the senile plaque formation in the transgenic mice. Our results showed that STZ-induced insulin-deficient hyperglycemia caused the pathophysiology of AD in APP/PS1 transgenic mice by modulating the AGEs/RAGE/NF-kappaB pathway. CONCLUSIONS: Our study suggests that there is a close linkage of DM and cerebral amyloidosis in the pathogenesis of AD. PMID- 24228860 TI - Highly ordered silicon pillar arrays as platforms for planar chromatography. AB - Unlike HPLC, there has been sparse advancement in the stationary phases used for planar chromatography. Nevertheless, modernization of planar chromatography platforms can further highlight the technique's ability to separate multiple samples simultaneously, utilize orthogonal separation formats, image (detect) separations without rigorous temporal demands, and its overall simplicity. This paper describes the fabrication and evaluation of ordered pillar arrays that are chemically modified for planar chromatography and inspected by fluorescence microscopy to detect solvent development and analyte bands (spots). Photolithography, in combination with anisotropic deep reactive ion etching, is used to produce uniform high aspect ratio silicon pillars. The pillar heights, diameters, and pitch variations are approximately 15-20 MUm, 1-3 MUm, and 2-6 MUm, respectively, with the total pillar array size typically 1 cm * 3 cm. The arrays are imaged using scanning electron microscopy in order to measure the pillar diameter and pitch as well as analyze the pillar sidewalls after etching and stationary phase functionalization. These fluidic arrays will enable exploration of the impact on mass transport and chromatographic efficiency caused by altering the pillar array morphology. A C18 reverse stationary phase (RP), common RP solvents that are transported by traditional but uniquely rapid capillary flow, and Rhodamine 6G (R6G) as the preliminary analyte are used for this initial evaluation. The research presented in this article is aimed at understanding and overcoming the unique challenges in developing and utilizing ordered pillar arrays as a new platform for planar chromatography: focusing on fabrication of expansive arrays, studies of solvent transport, methods to create compatible sample spots, and an initial evaluation of band dispersion. PMID- 24228861 TI - Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines. AB - BACKGROUND: Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. DISCUSSION: The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. CONCLUSIONS: Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine. PMID- 24228862 TI - Long-term efficacy of a printed or a Web-based tailored physical activity intervention among older adults. AB - BACKGROUND: This study provides insight into the long-term efficacy (i.e. 12 month results) of the Web-based or print-delivered tailored Active Plus intervention (with and without environmental approach) to promote physical activity (PA) among the over-fifties. Differences in effect among subgroups are studied as well. METHODS: Intervention groups (i.e. print-delivered basic (PB; N = 439), print-delivered environmental (PE; N = 435), Web-based basic (WB; N = 423), Web-based environmental (WE; N = 432)) and a waiting list control group (N = 411) were studied in a clustered randomized controlled trial. Intervention participants received tailored advice three times within 4 months. Long-term effects (12 months after the intervention has started, i.e. 8 months after the intervention was completed) on PA (i.e. self-reported weekly minutes and days of sufficient PA) were tested using multilevel linear regression analyses. Participants' age, gender, BMI, educational level, PA intention and the presence of a chronic physical limitation were considered to be potential moderators of the effect. RESULTS: Overall, the Active Plus intervention was effective in increasing weekly days of sufficient PA (B=0.49; p=.005), but ineffective in increasing weekly minutes of PA (B=84.59; p=.071). Per intervention condition analysis showed that the PB-intervention (B(days)=0.64; p=.002; B(min)=111.36; p=.017) and the PE-intervention (B(days)=0.70; p=.001; B(min)=157.41; p=.001) were effective in increasing days and minutes of PA. Neither Web-based conditions significantly increased PA, while the control group decreased their PA. In contrast to the intervention effect on minutes of PA, the effect on weekly days of PA was significantly moderated by the participants' baseline intention to be sufficiently physically active. CONCLUSIONS: In general, after 12 months the print-delivered interventions resulted in stronger effects than the Web-based interventions. The participants' baseline intention was the only significant moderator of the intervention effect. All other assessed user characteristics did not significantly moderate the effect of the intervention, which might indicate that the intervention is sufficiently tailored to the different participant characteristics. Additional efforts should be taken to increase the sustainability of Web-based interventions. TRIAL REGISTRATION: Dutch Trial Register: NTR2297. PMID- 24228863 TI - Pacific ciguatoxins in food web components of coral reef systems in the Republic of Kiribati. AB - Ciguatera fish poisoning (CFP) is a foodborne illness caused by consumption of coral reef fishes contaminated by ciguatoxins (CTXs); of the known CTX congeners, the Pacific ciguatoxins (P-CTXs) are the most toxic. Little is known about the trophodynamics of P-CTXs in coral reef systems. The present study explores the distribution, transfer, and trophic magnification of P-CTX-1, -2, and -3 in coral reef systems with high (ciguatoxic) and low (reference) ciguatoxicity in a CFP endemic nation by use of liquid chromatography-tandem mass spectrometry (LC MS/MS). In ciguatoxic coral reef systems, P-CTXs were detected in 54% of herbivorous fishes [total P-CTXs <0.500-1670 pg/g wet weight (ww)], 72% of omnivorous fishes (<0.500-1810 pg/g ww), and 76% of carnivorous fishes (<0.500-69 500 pg/g ww), as well as a lobster ( Panulirus penicillatus ; 2.36 pg/g ww) and an octopus (Octopodidae; 2.56 pg/g ww). The dominant P-CTXs in grazers and piscivorous fishes were P-CTX-2 and -1, respectively. No significant correlation between P-CTX levels and lipid content in three target predatory fishes indicated that accumulation of P-CTXs does not depend on fat content. A weak but significant positive relationship was observed between delta(15)N and P-CTX-1 levels, but further investigation is required to confirm its biomagnification potential. PMID- 24228864 TI - Age-related changes of movement patterns in discrete Fitts' task. AB - BACKGROUND: Inspired by the framework of dynamical system theory, we aimed at exploring how the behavioural repertoire of the sensorimotor system can be reshaped with aging. Our reasoning was founded on the assumption that, with age, some of the existing patterns can be destabilized or even lost. In the present paper, this issue was investigated through the study of age-related changes in the movement patterns that are used to perform a discrete Fitts' task. We analysed the performance of two groups of participants (young and older adults) across nine task difficulty levels, obtained via manipulation of target width. RESULTS: Two movement patterns were revealed by the fact that increase in the index of the difficulty (ID) was accommodated through either the lengthening of both acceleration (AT) and deceleration (DT) times (co-variation pattern), or only DT (dissociation pattern). Analysis of the discontinuity in ID-AT relation showed that young participants switched from the co-variation to the dissociation pattern as ID increased. Pattern switching was accompanied by concomitant changes in the variability of AT/DT ratio. Older adults, on the other hand, used the dissociation pattern regardless of the ID. Consequently, they showed neither an abrupt discontinuity in ID-AT relation nor significant changes in the variability of AT/DT ratio across difficulty levels. Though the dissociation pattern was adaptive in young adults for high accuracy constraints, in older adults, it compromised task performance for lower difficulty levels. CONCLUSION: These findings support the view that aging may result in a compression of the neuro behavioural repertoire. In sensorimotor tasks, it can lead to a loss of multi stability in terms of available movement patterns, thereby compromising the ability of the neuro-musculo-skeletal system to adapt and face task constraints. PMID- 24228866 TI - Simulations of acid dissociation constants of polyprotic acids in near-critical and supercritical water. AB - This paper reports a molecular dynamics study on the dissociation of sulfuric acid and phosphoric acid in near-critical and supercritical water. pK(a) is known to vary as the temperature and pressure vary, and this variation has important implications for corrosion in supercritical water reaction vessels. This work uses the SPC/E water model and solutes based upon DFT calculations to examine both structural and thermodynamic properties of the dissociation processes. An increase in solute-solvent ordering is observed for larger charges, and this also corresponds to a lower rate of diffusion. All dissociation reactions become less favored with increasing temperature except pK(a1) for sulfuric acid which becomes significantly more favored until 748 K. PMID- 24228865 TI - Genetic diversity of Plasmodium falciparum among school-aged children from the Man region, western Cote d'Ivoire. AB - BACKGROUND: The genetic diversity of Plasmodium falciparum allows the molecular discrimination of otherwise microscopically identical parasites and the identification of individual clones in multiple infections. The study reported here investigated the P. falciparum multiplicity of infection (MOI) and genetic diversity among school-aged children in the Man region, western Cote d'Ivoire. METHODS: Blood samples from 292 children aged seven to 15 years were collected in four nearby villages located at altitudes ranging from 340 to 883 m above sea level. Giemsa-stained thick and thin blood films were prepared and examined under a microscope for P. falciparum prevalence and parasitaemia. MOI and genetic diversity of the parasite populations were investigated using msp2 typing by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Plasmodium falciparum prevalence and parasitaemia were both found to be significantly lower in the highest altitude village. Genotyping of the isolates revealed 25 potentially new msp2 alleles. MOI varied significantly across villages but did not correlate with altitude nor children's age, and only to a limited extent with parasitaemia. An analysis of molecular variance (AMOVA) indicated that a small, but close to statistical significance (p = 0.07), fraction of variance occurs specifically between villages of low and high altitudes. CONCLUSIONS: Higher altitude was associated with lower prevalence of P. falciparum but not with reduced MOI, suggesting that, in this setting, MOI is not a good proxy for transmission. The evidence for partially parted parasite populations suggests the existence of local geographical barriers that should be taken into account when deploying anti-malarial interventions. PMID- 24228867 TI - Increasing the dose of acute rehabilitation: is there a benefit? AB - Rehabilitation interventions, including physiotherapy and occupational therapy, can improve patient outcomes; however, the optimal duration and frequency of inpatient rehabilitation interventions is uncertain. In a recent randomized controlled trial published in BMC Medicine, 996 patients in two publicly-funded Australian metropolitan rehabilitation facilities were assigned to physiotherapy and occupational therapy delivered Monday through Friday (five days/week control group) versus Monday through Saturday (six days/week intervention group). This increased dose of rehabilitation in the intervention group resulted in greater functional independence and quality of life at discharge, with a trend towards significant improvement at six-month follow-up. Moreover, the length of stay for the intervention group was shorter by two days (95% CI 0 to 4, P = 0.10). Hence, in the acute inpatient rehabilitation setting, a larger dose of physiotherapy and occupational therapy, via six versus five days/week treatment, improves patient outcomes and potentially reduces overall length of stay and costs. Please see related research: http://www.biomedcentral.com/1741-7015/11/198. PMID- 24228868 TI - The synthesis of vinylogous amidine heterocycles. AB - We report herein a convenient synthetic methodology for the conversion of meta dinitro heterocyclic rings to iminoquinones with vinylogous amidine functionality. These structures are found in nature, particularly in marine organisms, and may be important for the pigments and biological activity observed with such marine secondary metabolites. Using benzimidazole and indole ring systems we show the versatility of these vinylogous amidines for organic synthesis, including the following: transamination substitution reactions with virtually any primary amine, regional control of the substitution with substituents between the vinylogous amidine, and hydrolytic properties that can be controlled or optimized based on the properties of the chosen ring system. Taken together, this versatile chemistry and functionalization of organic molecules may be useful in the preparation of a variety of chemical products such as drug pharmacophores or assembling macromolecular structures. PMID- 24228869 TI - Vitellogenesis in the fruit fly, Drosophila melanogaster: antagonists demonstrate that the PLC, IP3/DAG, PK-C pathway is triggered by calmodulin. AB - In Drosophila melanogaster M. (Diptera: Drosophilidae), a phospholipase-C to proteininase-C signal cascade leads to the endocytic uptake of yolk precursor molecules. The data suggest that D. melanogaster has a phospholipase C/proteinkinase-C signaling pathway similar to that previously shown to be required for vitellogenesis in the milkweed bug, Oncopeltus fasciatus Dallas (Hemiptera: Lygaeidae). Calmodulin, derived from epithelial cells and transported to the oocytes via gap junctions, may trigger this pathway. To investigate this, a series of known antagonists to various elements of the pathway were used. W-7 (which prevents calmodulin binding to phospholipase-C), U-73122 (which prevents activation of phospholipase-C), verapamil (which blocks Ca(2+) release by IP3), HAG (which blocks diacylglycerol), and staurosporine (which inactivates proteinkinase-C) were each shown to inhibit endocytosis, thereby blocking formation of nascent yolk spheres. PMID- 24228870 TI - Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study. AB - PURPOSE: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs. METHODS: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues. RESULTS: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05). CONCLUSIONS: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver. PMID- 24228871 TI - Network component analysis provides quantitative insights on an Arabidopsis transcription factor-gene regulatory network. AB - BACKGROUND: Gene regulatory networks (GRNs) are models of molecule-gene interactions instrumental in the coordination of gene expression. Transcription factor (TF)-GRNs are an important subset of GRNs that characterize gene expression as the effect of TFs acting on their target genes. Although such networks can qualitatively summarize TF-gene interactions, it is highly desirable to quantitatively determine the strengths of the interactions in a TF-GRN as well as the magnitudes of TF activities. To our knowledge, such analysis is rare in plant biology. A computational methodology developed for this purpose is network component analysis (NCA), which has been used for studying large-scale microbial TF-GRNs to obtain nontrivial, mechanistic insights. In this work, we employed NCA to quantitatively analyze a plant TF-GRN important in floral development using available regulatory information from AGRIS, by processing previously reported gene expression data from four shoot apical meristem cell types. RESULTS: The NCA model satisfactorily accounted for gene expression measurements in a TF-GRN of seven TFs (LFY, AG, SEPALLATA3 [SEP3], AP2, AGL15, HY5 and AP3/PI) and 55 genes. NCA found strong interactions between certain TF-gene pairs including LFY -> MYB17, AG -> CRC, AP2 -> RD20, AGL15 -> RAV2 and HY5 -> HLH1, and the direction of the interaction (activation or repression) for some AGL15 targets for which this information was not previously available. The activity trends of four TFs - LFY, AG, HY5 and AP3/PI as deduced by NCA correlated well with the changes in expression levels of the genes encoding these TFs across all four cell types; such a correlation was not observed for SEP3, AP2 and AGL15. CONCLUSIONS: For the first time, we have reported the use of NCA to quantitatively analyze a plant TF GRN important in floral development for obtaining nontrivial information about connectivity strengths between TFs and their target genes as well as TF activity. However, since NCA relies on documented connectivity information about the underlying TF-GRN, it is currently limited in its application to larger plant networks because of the lack of documented connectivities. In the future, the identification of interactions between plant TFs and their target genes on a genome scale would allow the use of NCA to provide quantitative regulatory information about plant TF-GRNs, leading to improved insights on cellular regulatory programs. PMID- 24228872 TI - The New York stem cell foundation research institute's eighth annual translational stem cell research conference. PMID- 24228874 TI - Regulation of activity of transcription factor NF-kappaB by synthetic oligonucleotides. AB - Eukaryotic dimeric nuclear factor-kappaB (NF-kappaB) is one of the main transcription factors that activate expression of genes, products of which play the key role in development of cardiovascular pathologies, carcinogenesis, and inflammatory and viral diseases. In this review, the main attention is given to modulation of the transcription factor NF-kappaB activity by antisense oligonucleotides and oligonucleotide decoys. Also, current concepts about interactions between NF-kappaB dimers and DNA and general problems that arise in experimental use of synthetic oligonucleotides in vivo are discussed. PMID- 24228873 TI - Protein biosynthesis in mitochondria. AB - Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it has been in the spotlight of international research for many years. The mechanisms of protein biosynthesis in bacteria and in the eukaryotic cytoplasm are now understood in great detail. However, significantly less is known about translation in eukaryotic mitochondria, which is characterized by a number of unusual features. In this review, we summarize current knowledge about mitochondrial translation in different organisms while paying special attention to the aspects of this process that differ from cytoplasmic protein biosynthesis. PMID- 24228875 TI - Expression of chicken CTCF gene in COS-1 cells and partial purification of CTCF protein. AB - The chicken gene for transcription factor CTCF was expressed in COS-1 mammalian cells. The CTCF protein containing polyhistidine tag was partially purified using metallo-affinity and ion-exchange chromatography. The expressed protein localized in the cell nucleus and was shown to be functionally active in the electrophoretic mobility shift assay and specifically interacted with anti-CTCF antibodies. PMID- 24228876 TI - Targeted delivery of doxorubicin: drug delivery system based on PAMAM dendrimers. AB - Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4 degrees C and was absorbed by the cells at 37 degrees C. The covalent binding to G2-FITC of a vector protein, a recombinant fragment of the human alpha fetoprotein receptor-binding domain (rAFP3D), increased the binding and endocytosis efficiency more than threefold. Covalent conjugates of G2 with doxorubicin (Dox) obtained by acid-labile linking of cis-aconitic anhydride (CAA) without the vector protein (G2-Dox) and with the vector protein rAFP3D (rAFP3D-G2 Dox) were accumulated by the tumor cells with high efficiency. However, a selective effect was observed only in rAFP3D-G2-Dox, which also demonstrated high cytotoxic activity against the human ovarian adenocarcinoma SKOV3 cells and low cytotoxicity against human peripheral blood lymphocytes. Based on these results, rAFP3D-G2 conjugate is promising for selective delivery of antitumor drugs. PMID- 24228877 TI - Assay of insulator enhancer-blocking activity with the use of transient transfection. AB - We used a transient transfection of cultured cells with linearized plasmids to analyze the enhancer-blocking activity of potential insulators including the standard cHS4 chicken beta-globin insulator and several DNA fragments selected from the human genome sequence. About 60-80% of the potential insulators do reveal the enhancer-blocking activity when probed by the transient transfection assay. The activity of different sequences is characterized by certain tissue specificity and by dependence on the orientation of the fragments relative to the promoter. Thus, the transfection model may be used for quantitative analysis of the enhancer-blocking activity of the potential insulators. PMID- 24228878 TI - Comparison of oxygen consumption rates in minimally transformed BALB/3T3 and virus-transformed 3T3B-SV40 cells. AB - In the recent years, bioenergetics of tumor cells and particularly cell respiration have been attracting great attention because of the involvement of mitochondria in apoptosis and growing evidence of the possibility to diagnose and treat cancer by affecting the system of oxidative phosphorylation in mitochondria. In the present work, a comparative study of oxygen consumption in 3T3B-SV40 cells transformed with oncovirus SV40 and parental BALB/3T3 cells was conducted. Such fractions of oxygen consumption as "phosphorylating" respiration coupled to ATP synthesis, "free" respiration not coupled to ATP synthesis, and "reserve" or hidden respiration observed in the presence of protonophore were determined. Maximal respiration was shown to be only slightly decreased in 3T3B SV40 cells as compared to BALB/3T3. However, in the case of certain fractions of cellular respiration, the changes were significant. "Phosphorylating" respiration was found to be reduced to 54% and "reserve" respiration, on the contrary, increased up to 160% in virus-transformed 3T3B-SV40 cells. The low rate of "phosphorylating" respiration and high "reserve" respiration indicate that under normal incubation conditions the larger part of mitochondrial respiratory chains of the virus-transformed cells is in the resting state (i.e. there is no electron transfer to oxygen). The high "reserve" respiration is suggested to play an important role in preventing apoptosis of 3T3B-SV40 cells. PMID- 24228879 TI - Isolation and properties of flight muscle mitochondria of the bumblebee Bombus terrestris (L.). AB - This report describes the isolation procedure and properties of tightly coupled flight muscle mitochondria of the bumblebee Bombus terrestris (L.). The highest respiratory control index was observed upon oxidation of pyruvate, whereas the highest respiration rates were registered upon oxidation of a combination of the following substrates: pyruvate + malate, pyruvate + proline, or pyruvate + glutamate. The respiration rates upon oxidation of malate, glutamate, glutamate + malate, or succinate were very low. At variance with flight muscle mitochondria of a number of other insects reported earlier, B. terrestris mitochondria did not show high rates of respiration supported by oxidation of proline. The maximal respiration rates were observed upon oxidation of alpha-glycerophosphate. Bumblebee mitochondria are capable of maintaining high membrane potential in the absence of added respiratory substrates, which was completely dissipated by the addition of rotenone, suggesting high amount of intramitochondrial NAD-linked oxidative substrates. Pyruvate and alpha-glycerophosphate appear to be the optimal oxidative substrates for maintaining the high rates of oxidative metabolism of the bumblebee mitochondria. PMID- 24228880 TI - Glycogen synthase kinase-3beta is involved in C-reactive protein-induced endothelial cell activation. AB - C-reactive protein (CRP) is a significant contributor to atherosclerosis and a powerful predictor of cardiovascular risk. The role of CRP in endothelial cell (EC) activation has been extensively investigated, but the underlying mechanisms have not been fully elucidated. The effect of glycogen synthase kinase-3beta (GSK 3beta) on CRP-induced EC activation was evaluated in this study. We observed that CRP decreased endothelial nitric oxide synthase (eNOS) activity during EC activation. CRP also activated GSK-3beta by dephosphorylating its Ser9 level and reducing beta-catenin protein expression in a time-dependent manner. We also found that the GSK-3beta inhibitors TDZD-8 and SB415286 partially restored eNOS activity and suppressed the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. These data provide new evidence for the involvement of GSK-3beta in EC activation. PMID- 24228881 TI - A straightforward experimental approach to expression, purification, refolding, and enzymatic analysis of recombinant dengue virus NS2B(H)-NS3pro protease. AB - Dengue virus threatens around 2.5 billion people worldwide; about 50 million become infected every year, and yet no vaccine or drug is available for prevention and/or treatment. The flaviviral NS2B-NS3pro complex is indispensable for flaviviral replication and is considered to be an important drug target. The aim of this study was to develop a simple and generally applicable experimental strategy to construct, purify, and assay a highly active recombinant NS2B(H) NS3pro complex that would be useful for high-throughput screening of potential inhibitors. The sequence of NS2B(H)-NS3pro was generated by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H) NS3pro complex was expressed in E. coli predominantly as insoluble protein and purified to >95% purity by single-step immobilized metal affinity chromatography. SDS-PAGE followed by immunoblotting of the purified enzyme demonstrated the presence of the NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 37, 21, and 10 kDa bands, respectively. Kinetic parameters, Km, kcat, and kcat/Km for the fluorophore-linked protease model substrate Ac-nKRR-amc were obtained using inner-filter effect correction. The kinetic parameters Km, kcat, and kcat/Km for Ac-nKRR-amc substrate were 100 uM, 0.112 s(-1), and 1120 M( 1).s(-1), respectively. A simplified procedure for the cloning, overexpression, and purification of the NS2B(H)-NS3pro complex was applied, and a highly active recombinant NS2B(H)-NS3pro complex was obtained that could be useful for the design of high-throughput assays aimed at flaviviral inhibitor discovery. PMID- 24228882 TI - Modulation of enzymatic activity of dengue virus nonstructural protein NS3 nucleoside triphosphatase/helicase by poly(U). AB - The nonstructural protein 3 (NS3) appears to be the most promising target for anti-flavivirus therapy because of its multiple enzymatic activities that are indispensable for virus replication. NS3 of dengue virus type 2 (DEN2) is composed of two domains, a serine protease in the N-terminal domain (NS3pro) and RNA-stimulated nucleoside triphosphatase (NTPase)/RNA helicase at the C-terminus (NS3h). NS3 plays an important role in viral replication and the coordinated regulation of all the catalytic activities in the full-length NS3 protein. In this study, a plasmid harboring the NS3 helicase domain (NS3h) was constructed by PCR. The 56.5 kDa NS3h protein was purified by metal-chelate affinity chromatography followed by renaturation, mediated by artificial chaperone assisted refolding, which yielded the active helicase. NTPase activity was assayed with Malachite Green. The NTPase activity in the presence of poly(U) showed a higher turnover number (kcat) and a lower Km value than without poly(U). The activity increased approximately fourfold in the presence of polynucleotides. This indicates that NTPase activity of dengue NS3 can be stimulated by polynucleotides. A helicase assay based on internal fluorescence quenching was conducted using short internally quenched DNA oligonucleotides as substrates. Significant fluorescence signaling increase was observed in the absence of polynucleotides such as poly(U). No unwinding activity was observed with addition of poly(U). The approach we describe here is useful for the further characterization of substrate specificity and for the design of high-throughput assays aimed at discovery of inhibitors against NS3 NTPase/helicase activities. PMID- 24228883 TI - Coordination in gene expression during atherogenesis. AB - General tendencies in the regulation of gene expression during atherogenesis were investigated using correlation analysis for 34 mRNA species of several functional groups. The contents of mRNA were measured by quantitative PCR in samples of human aortal intima containing no lesions or atherosclerotic lesions of types I (initial lesions), II (fatty streaks), and Va (fibroatheromas). The coupling between mRNA contents in lesions and the same mRNAs in intact tissue was found to descend in the course of the disease progression. The data are in accordance with the opinion that successive morphologic types of atherosclerotic lesions correspond to steps of atherogenesis. In addition, the contents of individual mRNA species could correlate with each other within the given sample type, the extent of this coupling rising along with the disease progression. The exception from this rule was a collapse in coupling for several functional groups of mRNA in lesions of type I. This collapse could indicate special position of these lesions in pathogenesis. Statistically significant correlations between mRNAs found in samples of all four types comprised in total about 50% of all possible correlations. 66% of these correlations were conservative, i.e. observed in at least two sample types. By coupling-strength, the studied mRNAs could be divided into four clusters whose composition significantly varied along with the disease progression. The disease progression was also associated with decline in number of regulatory factors that determine coordination in expression of the analyzed genes. PMID- 24228884 TI - Polyphosphates and exopolyphosphatase activities in the yeast Saccharomyces cerevisiae under overexpression of homologous and heterologous PPN1 genes. AB - The role of exopolyphosphatase PPN1 in polyphosphate metabolism in fungi has been studied in strains of Saccharomyces cerevisiae transformed by the yeast PPN1 gene and its ortholog of the fungus Acremonium chrysogenum producing cephalosporin C. The PPN1 genes were expressed under a strong constitutive promoter of the gene of glycerol aldehyde-triphosphate dehydrogenase of S. cerevisiae in the vector pMB1. The yeast strain with inactivated PPN1 gene was transformed by the above vectors containing the PPN1 genes of S. cerevisiae and A. chrysogenum. Exopolyphosphatase activity in the transformant with the yeast PPN1 increased 28- and 11-fold compared to the mutant and parent PPN1 strains. The amount of polyphosphate in this transformant decreased threefold. Neither the increase in exopolyphosphatase activity nor the decrease in polyphosphate content was observed in the transformant with the orthologous PPN1 gene of A. chrysogenum, suggesting the absence of the active form of PPN1 in this transformant. PMID- 24228885 TI - Expression of duodenase-like protein in epitheliocytes of Brunner's glands in human duodenal mucosa. AB - A duodenase, a protease structurally related to human cathepsin G, was found earlier in bovine duodenal mucosa. It was demonstrated that under the influence of duodenase an enteropeptidase zymogen is activated in vitro showing the possible participation of duodenase in the cascade of activation of digestive enzymes. To identify a duodenase functional analog in human duodenum, an immunofluorescence study of duodenal mucosa was conducted by confocal microscopy using antibodies to human cathepsin G and to bovine duodenase. The previously unknown place of synthesis and secretion of cathepsin G - Paneth cells located at the bottom of Lieberkuhn crypts - was revealed. Binding of cathepsin G-specific antibodies in a rough endoplasmic reticulum zone and in the cryptal duct was observed. Duodenase-specific immunofluorescence but not that of cathepsin G was found in the epitheliocytes and secretory ducts of Brunner's glands, which are characteristic sites of duodenase biosynthesis in cattle. Binding of CD14 specific antibodies in the Brunner's glands, where the antibodies co-localized with the antibodies to duodenase, was also demonstrated. These data indicate the presence of a protein immunologically similar to duodenase in the human duodenal mucosa. Our study demonstrated the absence of its co-localization with cathepsin G in Brunner's glands. PMID- 24228886 TI - Escherichia coli signal peptidase recognizes and cleaves the signal sequence of alpha-amylase originating from Bacillus licheniformis. AB - The gene encoding the alpha-amylase from Bacillus licheniformis was cloned, with and without the native signal sequence, and expressed in Escherichia coli, resulting in the production of the recombinant protein in the cytoplasm as insoluble but enzymatically active aggregates. Expression with a low concentration of the inducer at low temperature resulted in the production of the recombinant protein in soluble form in a significantly higher amount. The protein produced with signal sequence was exported to the extracellular medium, whereas there was no export of the protein produced from the gene without the signal sequence. Similarly, the alpha-amylase activity in the culture medium increased with time after induction in case of the protein produced with signal sequence. Molecular mass determinations by MALDI-TOF mass spectrometry and N-terminal amino acid sequencing of the purified recombinant alpha-amylase from the extracellular medium revealed that the native signal peptide was cleaved by E. coli signal peptidase between Ala28 and Ala29. It seems possible that the signal peptide of alpha-amylase from B. licheniformis can be used for the secretion of other recombinant proteins produced using the E. coli expression system. PMID- 24228887 TI - Spliceosomal introns in the 5' untranslated region of plant BTL RING-H2 ubiquitin ligases are evolutionary conserved and required for gene expression. AB - BACKGROUND: Introns located close to the 5' end of a gene or in the 5' untranslated region often exert positive effects on gene expression. This effect, known as intron-mediated enhancement (IME), has been observed in diverse eukaryotic organisms, including plants. The sequences involved in IME seem to be spread across the intron and function in an additive manner. The IMEter algorithm was developed to predict plant introns that may enhance gene expression. We have identified several plant members of the BTL class of E3s, which may have orthologs across eukaryotes, that contain a 5'UTR intron. The RING finger E3 ligases are key enzymes of the ubiquitination system that mediate the transfer of ubiquitin to substrates. RESULTS: In this study, we retrieved BTL sequences from several angiosperm species and found that 5'UTR introns showing a strong IMEter score were predicted, suggesting that they may be conserved by lineage. Promoter GUS fusion lines were used to confirm the IME effect of these 5'UTR introns on gene expression. IMEter scores of BTLs were compared with the 5'UTR introns of two gene families MHX and polyubiquitin genes. CONCLUSIONS: Analysis performed in two Arabidopsis BTL E3 ligases genes indicated that the 5'UTR introns were essential for gene expression in all the tissues tested. Comparison of the average 5'UTR intron size on three gene families in ten angiosperm species suggests that a prevalent size for a 5'UTR intron is in the range of 600 nucleotides, and that the overall IMEter score within a gene family is preserved across several angiosperms. Our results indicated that gene expression dependent on a 5'UTR intron is an efficient regulatory mechanism in BTL E3 ligases that has been preserved throughout plant evolution. PMID- 24228888 TI - Revision and extension of Eco-LCA metrics for sustainability assessment of the energy and chemical processes. AB - Ecologically based life cycle assessment (Eco-LCA) is an appealing approach for the evaluation of resources utilization and environmental impacts of the process industries from an ecological scale. However, the aggregated metrics of Eco-LCA suffer from some drawbacks: the environmental impact metric has limited applicability; the resource utilization metric ignores indirect consumption; the renewability metric fails to address the quantitative distinction of resources availability; the productivity metric seems self-contradictory. In this paper, the existing Eco-LCA metrics are revised and extended for sustainability assessment of the energy and chemical processes. A new Eco-LCA metrics system is proposed, including four independent dimensions: environmental impact, resource utilization, resource availability, and economic effectiveness. An illustrative example of comparing assessment between a gas boiler and a solar boiler process provides insight into the features of the proposed approach. PMID- 24228889 TI - Section 3. A discussion of flexible dosing and patient-centered therapy: highlights of the asthma summit 2009: beyond the guidelines. AB - Despite positive clinical experience and the published clinical benefits of monotherapy with low-or medium-dose inhaled corticosteroids or combination therapy with ICS + long-acting beta-agonist to treat asthma, many patients remain suboptimally controlled. Alternative approaches are needed, and 3 options that have had some success are: 1) using the patient's level of inflammation by established biomarkers to set treatment; 2) self-management incorporating flexible dosing; and 3) using a single inhaler for rescue and maintenance therapy. Which strategy for which patient depends ultimately on the individual patient's disease burden, life-style, comorbidities, preferences, and his or her ability to self-manage the disease, including assessing symptoms and adhering with therapy. PMID- 24228890 TI - A qualitative study of legal and social justice needs for people with aphasia. AB - This paper presents an exploratory investigation of situations in which people with aphasia may be vulnerable to legal and access to justice issues. The study used a qualitative descriptive approach to analyse 167 de-identified transcriptions of previously collected interviews, with 50 participants with mild to-severe aphasia following stroke, 48 family members, and their treating speech language pathologists. Situations experienced by people with aphasia and their family members were coded using key-word searches based on the previously published framework developed by Ellison and colleagues to describe situations of vulnerability to legal and access to justice needs for older people. Health and financial and consumer situations were most frequently identified in the data. Additionally, there were a number of situations found specifically relating to people with aphasia involving their signatures and credit card use. Instances of discrimination and abuse were also identified, and, although infrequent, these issues point to the profound impact of aphasia on the ability to complain and, hence, to ensure rights to care are upheld. The findings of this study are consistent with previous research in suggesting that legal and access to justice needs are an important issue for people with aphasia and their families. PMID- 24228891 TI - Research priorities for child and adolescent physical activity and sedentary behaviours: an international perspective using a twin-panel Delphi procedure. AB - BACKGROUND: The quantity and quality of studies in child and adolescent physical activity and sedentary behaviour have rapidly increased, but research directions are often pursued in a reactive and uncoordinated manner. AIM: To arrive at an international consensus on research priorities in the area of child and adolescent physical activity and sedentary behaviour. METHODS: Two independent panels, each consisting of 12 experts, undertook three rounds of a Delphi methodology. The Delphi methodology required experts to anonymously answer questions put forward by the researchers with feedback provided between each round. RESULTS: The primary outcome of the study was a ranked set of 29 research priorities that aimed to be applicable for the next 10 years. The top three ranked priorities were: developing effective and sustainable interventions to increase children's physical activity long-term; policy and/or environmental change and their influence on children's physical activity and sedentary behaviour; and prospective, longitudinal studies of the independent effects of physical activity and sedentary behaviour on health. CONCLUSIONS: These research priorities can help to guide decisions on future research directions. PMID- 24228892 TI - Improving global health governance to combat counterfeit medicines: a proposal for a UNODC-WHO-Interpol trilateral mechanism. AB - BACKGROUND: Perhaps no greater challenge exists for public health, patient safety, and shared global health security, than fake/falsified/fraudulent, poor quality unregulated drugs, also commonly known as "counterfeit medicines", now endemic in the global drug supply chain. Counterfeit medicines are prevalent everywhere, from traditional healthcare settings to unregulated sectors, including the Internet. These dangerous medicines are expanding in both therapeutic and geographic scope, threatening patient lives, leading to antimicrobial resistance, and profiting criminal actors. DISCUSSION: Despite clear global public health threats, surveillance for counterfeit medicines remains extremely limited, with available data pointing to an increasing global criminal trade that has yet to be addressed appropriately. Efforts by a variety of public and private sector entities, national governments, and international organizations have made inroads in combating this illicit trade, but are stymied by ineffectual governance and divergent interests. Specifically, recent efforts by the World Health Organization, the primary international public health agency, have failed to adequately incorporate the broad array of stakeholders necessary to combat the problem. This has left the task of combating counterfeit medicines to other organizations such as UN Office of Drugs and Crime and Interpol in order to fill this policy gap. SUMMARY: To address the current failure of the international community to mobilize against the worldwide counterfeit medicines threat, we recommend the establishment of an enhanced global health governance trilateral mechanism between WHO, UNODC, and Interpol to leverage the respective strengths and resources of these organizations. This would allow these critical organizations, already engaged in the fight against counterfeit medicines, to focus on and coordinate their respective domains of transnational crime prevention, public health, and law enforcement field operations. Specifically, by forming a global partnership that focuses on combating the transnational criminal and patient safety elements of this pre-eminent global health problem, there can be progress against counterfeit drugs and their purveyors. PMID- 24228895 TI - Molecular dynamics simulations of the protonated G4 PAMAM dendrimer in an ionic liquid system. AB - Molecular dynamics simulations have been carried out for the ionic liquid system constituted by totally protonated PAMAM-EDA cations and Tf2N(-) anions. The conformational characteristics of the PMAM dendrimer (particularly the density profile around the dendrimer center) are compared with those obtained for the same dendrimer in water. We also investigate other features, such as the location of anions relative to the dendrimer molecules, and the interpenetration of the dendrimer cations in the ionic liquid system. It is shown that a substantial amount of anions are present in the outer part of the dendrimer, screening repulsive contacts between different cation molecules and favoring ionic conductivity. Dendrimer cations in the ionic liquid exhibit a significant degree of overlap. PMID- 24228896 TI - The structures of salicylate surfactants with long alkyl chains in non-aqueous media. AB - The self-assembled structures formed by alkyl salicylate surfactants, as a function of metal headgroup counterion, in dodecane and toluene have been investigated. Results from optical microscopy are combined with small angle neutron scattering to show that moisture in the organic phase can have a dramatic effect on the observed structures. A simple acidic cation produces a cluster of surfactant chains irrespective of the oil type or presence of water. However, systems with an alkali metal counterion (potassium or sodium) result in cylindrical micelles in dry dodecane changing to lamellar structures in the wet case and fuzzy spheres in dry toluene changing to bidisperse emulsions with the presence of water. However, if magnesium or calcium counterions are used, this leads to different structures, depending on the oil type and the presence of moisture. PMID- 24228894 TI - Effect of oral nitrates on pulse pressure and arterial elasticity in patients aged over 65 years with refractory isolated systolic hypertension: study protocol for a randomized controlled trial. AB - BACKGROUND: Isolated systolic hypertension is a highly prevalent disease among the elderly. The little available evidence on the efficacy of nitrates for treating the disease is based on small experimental studies. METHODS/DESIGN: We performed a multicenter, randomized, double-blind, phase III, placebo-controlled trial in 154 patients aged over 65 years with refractory isolated systolic hypertension. Patients were randomized to placebo or 40 mg/day of extended release isosorbide mononitrate added to standard therapy and titrated to 60 mg/day at week 6 if blood pressure exceeded 140/90 mmHg.The primary objective was to assess the effect on clinical pulse pressure of extended-release isosorbide mononitrate added to standard therapy in patients aged over 65 years with refractory isolated systolic hypertension after 3 months of treatment.The secondary objectives were as follows: to quantify the effect of adding the study drug on central blood pressure and vascular compliance using the augmentation index and pulse wave velocity; to evaluate the safety profile by recording adverse effects (frequency, type, severity) and the percentage of patients who had to withdraw from the trial because of adverse events; to quantify the percentage of patients who reach a clinical systolic blood pressure <140 mmHg or <130 mmHg measured by ambulatory blood pressure monitoring; and to quantify the change in pulse pressure measured by ambulatory blood pressure monitoring. DISCUSSION: Few clinical trials have been carried out to test the effect of oral nitrates on isolated systolic hypertension, even though these agents seem to be effective. Treatment with extended-release isosorbide mononitrate could improve control of systolic blood pressure without severe side effects, thus helping to reduce the morbidity and mortality of the disease. TRIAL REGISTRATION: EUDRACT Number: 2012-002988-10. PMID- 24228897 TI - Improved synthesis of carbon-clad silica stationary phases. AB - Previously, we described a novel method for cladding elemental carbon onto the surface of catalytically activated silica by a chemical vapor deposition (CVD) method using hexane as the carbon source and its use as a substitute for carbon clad zirconia.1,2 In that method, we showed that very close to exactly one uniform monolayer of Al (III) was deposited on the silica by a process analogous to precipitation from homogeneous solution in order to preclude pore blockage. The purpose of the Al(III) monolayer is to activate the surface for subsequent CVD of carbon. In this work, we present an improved procedure for preparing the carbon-clad silica (denoted CCSi) phases along with a new column packing process. The new method yields CCSi phases having better efficiency, peak symmetry, and higher retentivity compared to carbon-clad zirconia. The enhancements were achieved by modifying the original procedure in three ways: First, the kinetics of the deposition of Al(III) were more stringently controlled. Second, the CVD chamber was flushed with a mixture of hydrogen and nitrogen gas during the carbon cladding process to minimize generation of polar sites by oxygen incorporation. Third, the fine particles generated during the CVD process were exhaustively removed by flotation in an appropriate solvent. PMID- 24228898 TI - Formation of functionalized 2H-azirines through PhIO-mediated trifluoroethoxylation and azirination of enamines. AB - A variety of enaminones and enamine carboxylic esters were converted to trifluoroethoxylated 2H-azirines through reactions with PhIO in trifluoroethanol (TFE). The cascade reaction is postulated to proceed via a PhIO-mediated oxidative trifluoroethoxylation and a subsequent azirination of the alpha trifluoroethoxylated enamine intermediates. PMID- 24228899 TI - Stereoselective tandem cascade furan cycloadditions. AB - Oligofurans linked by a rigid tether undergo tandem cycloaddition reactions with high stereoselectivity. The reaction of bisfurans with dimethyl acetylenedicarboxylate (DMAD) involves tandem [4 + 2]/[4 + 2] cycloadditions in a pincer mode. The reaction of oligofurans with arynes involves stereoselective tandem [4 + 2]/[4 + 2] cycloaddition reactions in a domino mode. The corresponding aryne adducts have been transformed into extended perylene derivatives by deoxygenation and aromatization with HCl/EtOH. PMID- 24228902 TI - Identification and partial characterization of midgut proteases in the lesser mulberry pyralid, Glyphodes pyloalis. AB - Proteolytic activities in digestive system extracts from the larval midgut of the lesser mulberry pyralid, Glyphodes pyloalis Walker (Lepidoptera: Pyralidae), were analyzed using different specific peptide substrates and proteinase inhibitors. High proteolytic activities were found at pH 10.0 and a temperature of 50 degrees C using azocasein as substrate. The trypsin was active in the pH range of 9.5- 12.0, with its maximum activity at pH 11.5. Ethylene diamine tetraacetic acid had the most inhibitory effect, and 44% inhibition was detected in the presence of this inhibitor. Phenyl methane sulfonyl floride and N-tosyl-L-phe chloromethyl ketone also showed considerable inhibition of larval azocaseinolytic activity, with 40.2 and 35.1% inhibition respectively. These data suggest that the midgut of larvae contains mainly metalloproteases and serine proteases, mainly chymotrypsin. The effect of several metal ions on the activity of proteases showed that NaCl, CaCl2, CoCl2 (5 and 10 mM), and MnCl2 (5mM) reduced the protease activity. The kinetic parameters of trypsin-like proteases using N benzoyl-L-arg-p-nitroanilide as substrate indicated that the Km and Vmax values of trypsin in the alimentary canal were 50.5 +/- 2.0 uM and 116.06 +/- 1.96 nmol min(-1) mg(-1) protein, respectively. Inhibition assays showed only small amounts of cysteine proteases were present in the G. pyloalis digestive system. The midgut digestive protease system of G. pyloalis is as diverse as that of any of the other polyphagous lepidopteran insect species, and the midgut of larvae contains mainly metalloproteases. Moreover, serine proteases and chymotrypsin also play main roles in protein digestion. Characterization of the proteolytic properties of the digestive enzymes of G. pyloalis offers an opportunity for developing appropriate and effective pest management strategies via metalloproteases and chymotrypsin inhibitors. PMID- 24228901 TI - A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial. AB - BACKGROUND: Physical exercise and a Mediterranean diet improve serum lipid profile. The present work studied whether red wine has an effect on top of a lipid-lowering lifestyle in patients with carotid atherosclerosis. METHODS: A prospective randomised unblinded trial was performed from 2009 to 2011 in 108 patients with carotid atherosclerosis, 65% of whom were already on statin therapy with a low mean LDL of 104.9 mg/dl. Half of them were advised to follow a modified Mediterranean diet and to perform moderate physical exercise during 30 min/day (lifestyle changes) for 20 weeks. Within these two groups half of the patients were randomised either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. RESULTS: LDL was significantly lowered by 7% in the lifestyle-changes group compared to the no-lifestyle-changes group (p = 0.0296) after 20 weeks. Lifestyle changes lowered the LDL/HDL ratio after 20 weeks by 8% (p = 0.0242) and red wine independently by 13% (p = 0.0049). The effect on LDL/HDL ratio after 20 weeks was, however, more pronounced in the non-LC group. Total cholesterol (-6%; p = 0.0238) and triglycerides (-13%; p = 0.0361) were lowered significantly by lifestyle changes after 20 weeks compared to the no-lifestyle-changes group. Lipoprotein (a) was not significantly affected by any intervention. The given results are per ITT analysis. CONCLUSIONS: Lifestyle changes including a modified Mediterranean diet and physical exercise as well as a glass of red wine daily improve independently the LDL/HDL ratio in patients with carotid arteriosclerosis even though the vast majority of them was already on statin therapy. PMID- 24228903 TI - Rates and mechanisms of Zn2+ adsorption on a meat and bonemeal biochar. AB - Biochars produced from meat and bonemeal (MBM) waste materials contain large amounts of calcium phosphate and are potentially useful sorbents for the remediation of metals. Because the reactivity of biochars depends strongly upon the conditions used in their production, the objective of this study was to evaluate the rates and mechanisms of Zn sorption onto a commercially supplied MBM biochar prior to its application in a field-scale revegetation project. Sorption experiments varying pH, time, and Zn concentration found that, above pH 6.1, Zn adsorbed to MBM biochar quickly (within 5 h) with a maximum adsorption capacity of 0.65 mmol Zn g(-1). Synchrotron-based Zn K-edge extended X-ray absorption fine structure spectroscopy was consistent with a tetrahedral Zn bound to phosphate groups in a monodentate inner-sphere surface complex for all conditions tested. With an acidification pretreatment and at more acidic pH, MBM biochar causes precipitation of a ZnPO4 phase. On the basis of these results, this MBM biochar has a high capacity to rapidly adsorb Zn in adsorption experiments and can be considered a promising sorbent for Zn remediation of contaminated soils. PMID- 24228904 TI - Antimicrobial polycarbonates: investigating the impact of balancing charge and hydrophobicity using a same-centered polymer approach. AB - Biodegradable antimicrobial polymers are a promising solution for combating drug resistant microbes. When designing these materials, the balance between charge and hydrophobicity significantly affects the antimicrobial activity and selectivity toward microbes over mammalian cells. Furthermore, where the charge and hydrophobicity is located on the molecules has also proven to be significant. A series of antimicrobial homopolymer polycarbonates were synthesized, where the hydrophobic/hydrophilic balance was controlled by varying the spacer between the charged quaternary ammonium moiety and the polymer backbone (a "same-centered" structure where the hydrophobic moiety is directly attached to the charged moiety). These homopolymers were active against all microbes tested but depending on the spacer length some hemolytic activity was observed. To reduce the polymer hemolytic activity we systematically varied the polymer composition by copolymerizing the different monomers used in the "same center" homopolymers. By maintaining charge on each repeat unit but copolymerizing monomers having varied hydrophobic side chain lengths, polymers with high activity and selectivity were achieved. In addition, these macromolecules act via a membrane disruption mechanism, making them less likely to induce resistance. PMID- 24228900 TI - So depression is an inflammatory disease, but where does the inflammation come from? AB - BACKGROUND: We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is 'what is the source of this chronic low-grade inflammation?' DISCUSSION: This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. SUMMARY: The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder. PMID- 24228905 TI - Perioperative blood transfusions and survival in patients with non-small cell lung cancer: a retrospective study. AB - BACKGROUND: Perioperative blood transfusions have been associated with poor clinical outcomes in the context of oncological surgery. Current literature is inconclusive whether blood transfusions are linked to shorter recurrence free and overall survival after lung cancer surgery. We hypothesize that blood transfusions in patients undergoing surgery for non-small cell lung cancer are associated with poor oncological survival. METHODS: After IRB approval, perioperative data from 636 patients who underwent lung cancer surgery was collected. Patients were evaluated for time to tumor recurrence and overall survival. RESULTS: 60 patients were transfused and 576 subjects were not. Patients who received transfusion were more likely to have more advanced disease (p = 0.018), and preoperative low hemoglobin concentrations (p < 0.0001) compared to non-transfused patients. In the multivariable Cox regression analysis, blood transfusion was associated with a significant reduction in recurrence free survival (p = 0.025), HR: 1.55 (95% CI: 1.06-2.27) and overall survival (p = 0.0002) HR: 2.04 (95% CI: 1.41-2.97). However, analysis after propensity score matching between the two groups revealed that the effect of blood transfusion was significant for reduction in overall survival (p = 0.0356), HR: 1.838 (95% CI: 1.04-3.22) but not for recurrence free survival (p = 0.1460), HR: 1.493 (95% CI: 0.87-2.56). CONCLUSIONS: Perioperative administration of red blood cells appears be associated with a decreased overall survival but not recurrence free survival after lung cancer surgery. Our study has the limitations of a retrospective review. Hence, our results should be confirmed by a prospective randomized control trial. PMID- 24228906 TI - The CARE guidelines: consensus-based clinical case reporting guideline development. AB - BACKGROUND: A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design.Primary Objective. Develop, disseminate, and implement systematic reporting guidelines for case reports. METHODS: We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. RESULTS: This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. CONCLUSIONS: We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery. PMID- 24228907 TI - Loss and growth: identity processes with distinct and complementary impacts on well-being among those living with chronic illness. AB - The diagnosis and treatment of any chronic illness are a major source of stress for most individuals. Although many individuals living with chronic illness report experiencing growth that arises from this experience, studies have revealed mixed results regarding the association between reported growth and other aspects of psychological well-being. This pilot study examines the complementary and buffering influences of self-growth on self-loss in perceptions of physical and mental health among individuals living with HIV (N = 60). The sample was comprised of a racially/ethnically diverse sample of men and women ranging in age from 27 to 62. Measures included impact of illness on Self-Concept Scale, the Medical Outcomes Study HIV Health Survey, the HIV Symptom Index, and the Center for Epidemiological Studies Depression Scale. Regression analyses were conducted to examine the impact of self-growth and self-loss on self-reported bothersome symptoms and depression, controlling for demographic covariates and physical health. Self-loss accounted for a significant proportion of variance in both bothersome symptom reports and depression, after controlling for physical health. In multivariate analysis, self-growth appeared to buffer the negative impact of self-loss on bothersome symptoms, but not on depression. These data suggest that self-loss is a critical construct in understanding adaptation to chronic illness, and that identity processes may influence symptom perception and mental health outcomes above and beyond the impact of traditional measures of health status. PMID- 24228908 TI - Rumen microbes and microbial protein synthesis in Thai native beef cattle fed with feed blocks supplemented with a urea-calcium sulphate mixture. AB - The influence of slow-release urea ( urea-calcium sulphate mixture; U-CaS) in feed blocks on rumen micro-organisms, predominant cellulolytic bacteria, microbial protein synthesis and ecology was studied in Thai native beef cattle. Four animals with an initial body weight of 100 +/- 3.0 kg were randomly assigned to a 4 * 4 Latin square design with four dietary treatments (U-CaS in iso nitrogen feed blocks at 0, 120, 150 and 180 g/kg dry matter (DM), respectively; U CaS replaced urea). After 21 days of experimental feeding, rumen fluid was collected at 0 and 4 h after feeding. The mean intake of feed blocks and other feedstuffs offered (rice straw and concentrates) amounted to 0.3, 2.3 and 0.6 kg DM/day, respectively. Inclusion of U-CaS did not altered pH and temperature in the rumen. However, ruminal NH3-N concentration decreased quadratically (p < 0.05) in response to U-CaS inclusion, with the lowest value at 180 g U-CaS per kg feed block. With inclusion of U-CaS, the populations of rumen bacteria increased quadratically (p < 0.05) and counts of fungal zoospores were linearly enhanced (p < 0.05), being highest at 180 g U-CaS per kg feed block. Supplementation of U-CaS increased the concentration of total bacteria linearly (p < 0.05) and of Fibrobacter succinogenes quadratically (p < 0.05), whereas Ruminococcus flavefaciens and Ruminococcus albus were not affected by dietary treatments. Microbial crude protein yield and efficiency of microbial nitrogen (N) synthesis were linearly increased with different levels of U-CaS addition. Furthermore, current data clearly indicate that inclusion of U-CaS in feed blocks can affect micro-organism diversity and major cellulolytic bacteria. PMID- 24228909 TI - Effects of oregano on performance and immunmodulating factors in weaned piglets. AB - Many health effects can be attributed to the Mediterranean herb oregano (Origanum vulgare L.) and several studies demonstrated the improving effect on performance, changes in blood count, antibacterial, antifungal and immunmodulating abilities. The majority of these investigations were carried out with processed essential oil, while whole plant material was only used in a few studies. Thus, the aim of the present experiment was to test the effect of increasing proportions of dried oregano in piglet feed on health and performance, with a special focus on immune modulation. A total of 80 male castrated weaned piglets (body weight [BW] 7.9 kg +/- 1.0 kg) were used in a feeding experiment lasting 5 weeks. They were assigned to 4 experimental groups: a control diet, and three diets with an oregano supplementation at 2 g, 4 g and 8 g per kg feed, respectively, corresponding to 23.5 mg, 46.9 mg and 93.9 mg carvacrol/kg DM. After 3 weeks, half of each group was challenged with 5 ug lipopolysaccharides (LPS) per kg BW. Blood samples were collected 2 h after LPS stimulation and analysed for T-cell phenotypes, granulocyte activity, clinical-chemistry as well as white and red blood count. The results indicate no effects of oregano on performance. In contrast, oregano altered the lymphocyte proportion and the ratio of CD4(+) and CD8(+) T-cells as well as the triglyceride concentration in the serum of non-stimulated and in LPS stimulated piglets. In conclusion, whole plant supplementation of oregano to piglet feed altered immune-related parameters, but did not modulate the acute inflammatory response induced by LPS stimulation. PMID- 24228910 TI - Influence of dietary amino acid level on chemical body composition and performance of growing-finishing boars of two sire lines. AB - There is only little information available concerning the chemical body composition of growing-finishing boars. For that reason, a total of 26 entire male pigs (boars) of two different Pietrain sire lines were fed with different levels of dietary essential amino acids (EAA) and the influence of this treatment on performance and chemical body composition was evaluated. In addition, an initial group of eight boars (n = 4 per sire line) was slaughtered at approximately 21 kg live weight (LW). The other 26 boars were fed three different diets containing 11.5, 13.2 and 14.9 g lysine/kg during the grower period and 9.0, 10.4, 11.7 g lysine/kg during the finisher period, respectively. Other EAA were added in relation to lysine (Lys: Met + Cys: Thr: Trp: Val = 1: 0.60: 0.65: 0.18: 0.75). At a LW of approximately 122 kg these 26 boars (six groups with three to seven animals each) were also slaughtered. The effects of EAA level and sire line on fattening and slaughter performance was recorded, and body and weight gain composition were analysed. There were no significant effects of EAA level on performance or on chemical body composition. Boars sired with Pietrain line 1 demonstrated increased lean meat content and protein body content (p < 0.05) as compared to Pietrain line 2-sired boars. PMID- 24228911 TI - Addition of citrus pulp and apple pomace in diets for dogs: influence on fermentation kinetics, digestion, faecal characteristics and bacterial populations. AB - Fermentation kinetics, digestibility, faecal characteristics and bacterial populations (aerobes, anaerobes, lactobacilli, lactic acid bacteria, enterococci, coliforms and clostridia) of dog food mixed with citrus pulp and apple pomace were evaluated. The in vitro gas production of a pre-digested dog food mixed with 0, 30, 50 and 70 g/kg dry matter (DM) of citrus pulp or apple pomace was measured, and also an experiment with dogs fed the same dog food with or without the addition of 70 g/kg of either fresh citrus pulp or apple pomace was conducted. Gas production increased linearly (p < 0.001) and quadratically (p < 0.001) as fibre levels augmented. The inclusion of fibre sources in the diets resulted in higher faecal output (p =0.005) and defecation frequency (p < 0.001), and lower faecal pH (p < 0.001) and digestibility values (p < 0.01). Faecal consistencies and microbial populations did not differ among treatments. The addition of fresh citrus and apple was effective to stimulate the hindgut fermentation, but slightly depressed the digestion. PMID- 24228912 TI - The regulatory effects of resistant starch on glycaemic response in obese dogs. AB - The purpose of this study was to examine the inhibitory effects of resistant starch on postprandial glycaemic response in obese dogs. The changes in blood glucose concentrations and glycaemic index (GI) were chronologically determined after the administration of resistant and normal starches by nasal feeding. Resistant starch contained indigestible dextrin (IDD) and beta-cyclic dextrin (beta-CD). Soluble starch (SS) served as a control starch. Glucose concentrations reached their maximum 15 min after the administration of SS solutions, and decreased gradually during the experimental period. In contrast, after the administration of IDD solutions, increased glucose concentrations rapidly decreased to the initial values. After the administration of beta-CD solutions, glucose concentrations remained unchanged during this study. GI levels remained constant in the following order: beta-CD < IDD < SS. GI levels of dogs receiving IDD and beta-CD solutions were significantly lower as compared with those animals receiving SS solutions. In this study, nasal tube feeding was an effective method for evaluating glycaemic responses to various starches accurately. The present data revealed that resistant starches were useful materials in controlling nutritionally glucose concentrations in obese dogs. These results raise the possibility that resistant starches are valuable for dietetic treatment of diabetes and obesity in dogs. PMID- 24228916 TI - Contribution of psychological trauma to outcomes after traumatic brain injury: assaults versus sporting injuries. AB - Clinical research into outcomes after traumatic brain injury (TBI) frequently combines injuries that have been sustained through different causes (e.g., car accidents, assaults, and falls), the effect of which is not well understood. This study examined the contribution of injury-related psychological trauma-which is more commonly associated with specific types of injuries-to outcomes after nonpenetrating TBI in order to determine whether it may be having a differential effect in samples containing mixed injuries. Data from three groups that were prospectively recruited for two larger studies were compared: one that sustained a TBI as a result of physical assaults (i.e., psychologically traumatizing) and another as a result of sporting injuries (i.e., nonpsychologically traumatizing), as well as an orthopedic control group (OC). Psychosocial and emotional (postconcussion symptoms, injury-related stress, and depression), cognitive (memory, abstract reasoning, problem solving, and verbal fluency), and functional (general outcome; resumption of home, social, and work roles) outcomes were all assessed. The TBI(assault) group reported significantly poorer psychosocial and emotional outcomes and higher rates of litigation (criminal rather than civil) than both the TBI(sport) and OC groups approximately 6 months postinjury, but there were no differences in the cognitive or functional outcomes of the three groups. The findings suggest that the cause of a TBI may assist in explaining some of the differences in outcomes of people who have seemingly comparable injuries. Involvement in litigation and the cause of an injury may also be confounded, which may lead to the erroneous conclusion that litigants have poorer outcomes. PMID- 24228917 TI - Bacteria and phenoptosis. AB - Genetically programmed death of an organism, or phenoptosis, can be found not only in animals and plants, but also in bacteria. Taking into account intrapopulational relations identified in bacteria, it is easy to imagine the importance of phenoptosis in the regulation of a multicellular bacterial community in the real world of its existence. For example, autolysis of part of the population limits the spread of viral infection. Destruction of cells with damaged DNA contributes to the maintenance of low level of mutations. Phenoptosis can facilitate the exchange of genetic information in a bacterial population as a result of release of DNA from lysed cells. Bacteria use a special "language" to transmit signals in a population; it is used for coordinated regulation of gene expression. This special type of regulation of bacterial gene expression is usually active at high densities of bacteria populations, and it was named "quorum sensing" (QS). Different molecules can be used for signaling purposes. Phenoptosis, which is carried out by toxin-antitoxin systems, was found to depend on the density of the population; it requires a QS factor, which is called the extracellular death factor. The study of phenoptosis in bacteria is of great practical importance. The components that make up the systems ensuring the programmed cell death, including QS factor, may be used for the development of drugs that will activate mechanisms of phenoptosis and promote the destruction of pathogenic bacteria. Comparative genomic analysis revealed that the genes encoding several key enzymes involved in apoptosis of eukaryotes, such as paracaspases and metacaspases, apoptotic ATPases, proteins containing NACHT leucine-rich repeat, and proteases similar to mitochondrial HtrA-like protease, have homologs in bacteria. Proteomics techniques have allowed for the first time to identify the proteins formed during phenoptosis that participate in orderly liquidation of Streptomyces coelicolor and Escherichia coli cells. Among these proteins enzymes have been found that are involved in the degradation of cellular macromolecules, regulatory proteins, and stress-induced proteins. Future studies involving methods of biochemistry, genetics, genomics, proteomics, transcriptomics, and metabolomics should support a better understanding of the "mystery" of bacterial programmed cell death; this knowledge might be used to control bacterial populations. PMID- 24228918 TI - Arguments against non-programmed aging theories. AB - Until recently, non-programmed theories of biological aging were popular because of the widespread perception that the evolution process could not support the development and retention of programmed aging in mammals. However, newer evolutionary mechanics theories including group selection, kin selection, and evolvability theory support mammal programmed aging, and multiple programmed aging theories have been published based on the new mechanics. Some proponents of non-programmed aging still contend that their non-programmed theories are superior despite the new mechanics concepts. However, as summarized here, programmed theories provide a vastly better fit to empirical evidence and do not suffer from multiple implausible assumptions that are required by non-programmed theories. This issue is important because programmed theories suggest very different mechanisms for the aging process and therefore different mechanisms behind highly age-related diseases and conditions such as cancer, heart disease, and stroke. PMID- 24228919 TI - Perspectives of mitochondrial medicine. AB - Mitochondrial medicine was established more than 50 years ago after discovery of the very first pathology caused by impaired mitochondria. Since then, more than 100 mitochondrial pathologies have been discovered. However, the number may be significantly higher if we interpret the term "mitochondrial medicine" more widely and include in these pathologies not only those determined by the genetic apparatus of the nucleus and mitochondria, but also acquired mitochondrial defects of non-genetic nature. Now the main problems of mitochondriology arise from methodology, this being due to studies of mitochondrial activities under different models and conditions that are far from the functioning of mitochondria in a cell, organ, or organism. Controversial behavior of mitochondria ("friends and foes") to some extent might be explained by their bacterial origin with possible preservation of "egoistic" features peculiar to bacteria. Apparently, for normal mitochondrial functioning it is essential to maintain homeostasis of a number of mitochondrial elements such as mitochondrial DNA structure, membrane potential, and the system of mitochondrial quality control. Abrogation of these elements can cause a number of pathologies that have become subjects of mitochondrial medicine. Some approaches to therapy of mitochondrial pathologies are discussed. PMID- 24228920 TI - Fatal "triad": lipotoxicity, oxidative stress, and phenoptosis. AB - Negative factors, such as the "magnificent" five that includes alcoholism, smoking, unhealthy food, lack of movement, and negative emotions, accompany a person almost from birth and trigger powerful internal biochemical reactions leading to disastrous consequences. Those new deleterious reactions force the organism to mobilize all of its internal reserves to neutralize, at least temporarily, the destructive effects of these negative factors. As a result of this continuous struggle for survival, body parts degenerate, starting from connective tissue protein molecules to entire newly formed organs (such as adipose tissue). Today we can state with certainty that the reason for the majority of widespread pathologies causing premature aging and death, such as atherosclerosis and arterial hypertension, is exactly those external negative factors that a person voluntary introduces into their life. However, the margin of safety that Nature enclosed in the human body is really amazing, allowing light-minded and self-destructive people to live up to 60 years and longer. It is quite possible that the lifespan will increase up to 100 years and more if a person stops destroying themself with negative emotions and bad habits, including unhealthy food and overeating. This article examines possible interconnection between unhealthy overeating and the theory of programmed aging and phenoptosis. PMID- 24228921 TI - Phenoptosis as genetically determined aging influenced by signals from the environment. AB - Aging is a complex and not well understood process. Two opposite concepts try to explain its causes and mechanisms - programmed aging and aging of "wear and tear" (stochastic aging). To date, much evidence has been obtained that contradicts the theories of aging as being due to accumulation of various damages. For example, creation of adequate conditions for the functioning of the organism's components (appropriate microenvironment, humoral background, etc.) has been shown to cause partial or complete reversibility of signs of its aging. Programmed aging and death of an organism can be termed phenoptosis by analogy to the term apoptosis for programmed cell death (this term was first suggested by V. P. Skulachev). The necessity of this phenomenon, since A. Weismann, has been justified by the need for population renewal according to ecological and evolutionary requirements. Species-specific lifespan, age-dependent changes in expression pattern of genes, etc. are compatible with the concept of phenoptosis. However, the intraspecific rate of aging was shown to vary over of a wide range depending on living conditions. This means that the "aging program" is not set rigidly; it sensitively adjusts an individual to the specific realities of its habitat. Moreover, there are indications that in rather severe conditions of natural habitat the aging program can be completely cancelled, as the need for it disappears because of the raised mortality from external causes (high extrinsic mortality), providing fast turnover of the population. PMID- 24228922 TI - Effect of mitochondria-targeted antioxidant SkQ1 on programmed cell death induced by viral proteins in tobacco plants. AB - Programmed cell death (PCD) is the main defense mechanism in plants to fight various pathogens including viruses. The best-studied example of virus-induced PCD in plants is Tobacco mosaic virus (TMV)-elicited hypersensitive response in tobacco plants containing the N resistance gene. It was previously reported that the animal mitochondrial protein Bcl-xL, which lacks a homolog in plants, effectively suppresses plant PCD induced by TMV p50 - the elicitor of hypersensitive response in Nicotiana tabacum carrying the N gene. Our studies show that the mitochondria-targeted antioxidant SkQ1 effectively suppresses p50 induced PCD in tobacco plants. On the other hand, SkQ1 did not affect Poa semilatent virus TGB3-induced endoplasmic reticulum stress, which is followed by PCD, in Nicotiana benthamiana epidermal cells. These data suggest that mitochondria-targeted antioxidant SkQ1 can be used to study molecular mechanisms of PCD suppression in plants. PMID- 24228923 TI - Post-reproductive life span and demographic stability. AB - Recent field studies suggest that it is common in nature for animals to outlive their reproductive viability. Post-reproductive life span has been observed in a broad range of vertebrate and invertebrate species. But post-reproductive life span poses a paradox for traditional theories of life history evolution. The commonly cited explanation is the "grandmother hypothesis", which applies only to higher, social mammals. We propose that post-reproductive life span evolves to stabilize predator-prey population dynamics, avoiding local extinctions. In the absence of senescence, juveniles would be the most susceptible age class. If juveniles are the first to disappear when predation pressure is high, this amplifies the population's risk of extinction. A class of older, senescent individuals can help shield the juveniles from predation, stabilizing demographics and avoiding extinction. If, in addition, the life history is arranged so that the older individuals are no longer fertile, the stabilizing effect is further enhanced. PMID- 24228924 TI - Evidence for aging theories from the study of a hunter-gatherer people (Ache of Paraguay). AB - In the late seventies, a small tribal population of Paraguay, the Ache, living under natural conditions, was studied. Data from this population turn out to be useful for considerations about evolutionary hypotheses on the aging phenomenon. 1) Ache show an age-related increasing mortality, which strongly limits the mean duration of life, as observed in other studies on mammal and bird species. 2) According to current theories on aging, in the wild very few or no individual reach old age and, so, aging cannot be directly influenced by natural selection. However, data from our population show that a significant proportion of the population reaches in the wild 60 and 70 years of age. 3) Data from Ache are also in agreement with the observation about an inverse correlation between extrinsic mortality and deaths due to the age-related increasing mortality. 4) For many gerontologists, the age-related decline of vital functions is a consequence of the gradual decline of cell turnover, genetically determined and regulated by the declining duplication capacities of stem cells. The current interpretation is that these restrictions are a general defense against the proliferation of any tumoral mass. However, among wild Ache cancer is virtually unknown in non-elderly subjects, and only among older individuals are there deaths attributable to oncological diseases. Moreover, fitness decline begins long before oncological diseases have fatal effects in significant numbers. This completely disproves the current hypothesis, because a supposed defense against a deadly disease cannot exterminate a population before the disease begins to kill. These data are consistent with similar data from other species studied under natural conditions, and they bring new arguments against the non-adaptive interpretation of aging and in support of the adaptive interpretation. PMID- 24228925 TI - Age fluctuations in mortality of mice with mutation causing growth retardation. AB - Lifespan of mice over a number of consecutive generations of descendants of a male with a mutation causing growth retardation was studied. The mutant and normally developing (normal) mice were obtained by crossbreeding of mutant males with normal females from the same brood. The mutant females were infertile. Mortality of the mutant and normal mice was shown to fluctuate depending on age. The curve of dependence of lifespan on their serial number in a series of lifespan increase (mortality rank curve) had the form of evident steps for the mutant mice, while in normal mice this feature was less pronounced. These steps indicate that in the course of development of mice stages with low mortality are alternately replaced by stages with increased mortality. One month after birth, the first stage of stable development of mutant males and females is replaced by a stage with abnormally high mortality, which coincides with the period of their maximal backlog in weight compared to the normal animals. Within two months, surviving mutants catch up in weight with normally developing mice and externally become indistinguishable from them. The steps are reproduced on mortality rank curves in mutant and normal mice, both in groups of mice of different sexes and in parallel same-sex groups. The observed phenomenon is interpreted within the hypothesis of a genetic aging program in mice that provides periodic changes when stages of great viability are followed by stages of increased sensitivity to the external risk factors causing death. Less-expressed steps on mortality rank curves of normal females were shown to be enhanced by the removal from the sample of parous females and animals with tumors. Results of the study indicate the possibility of detecting in humans of ontogenesis-programmed stages of high and low sensitivity to external influences and the prospect of the development of effective measures to prevent risks of premature death. PMID- 24228926 TI - Advanced glycation of cellular proteins as a possible basic component of the "master biological clock". AB - During the last decade, evidence has been accumulating supporting the hypothesis that aging is genetically programmed and, therefore, precisely timed. This hypothesis poses a question: what is the mechanism of the biological clock that controls aging? Measuring the level of the advanced glycation end products (AGE) is one of the possible principles underlying the functioning of the biological clock. Protein glycation is an irreversible, non-enzymatic, and relatively slow process. Moreover, many types of cells have receptors that can measure AGE level. We propose the existence of a protein that has a lifespan comparable to that of the whole organism. Interaction of the advanced glycation end product generated from this protein with a specific AGE receptor might initiate apoptosis in a vitally important non-regenerating tissue that produces a primary juvenile hormone. This could result in the age-dependent decrease in the level of this hormone leading to aging of the organism. PMID- 24228927 TI - How does the body know how old it is? Introducing the epigenetic clock hypothesis. AB - Animals and plants have biological clocks that help to regulate circadian cycles, seasonal rhythms, growth, development, and sexual maturity. It is reasonable to suspect that the timing of senescence is also influenced by one or more biological clocks. Evolutionary reasoning first articulated by G. Williams suggests that multiple, redundant clocks might influence organismal aging. Some aging clocks that have been proposed include the suprachiasmatic nucleus, the hypothalamus, involution of the thymus, and cellular senescence. Cellular senescence, mediated by telomere attrition, is in a class by itself, having recently been validated as a primary regulator of aging. Gene expression is known to change in characteristic ways with age, and in particular DNA methylation changes in age-related ways. Herein, I propose a new candidate for an aging clock, based on epigenetics and the state of chromosome methylation, particularly in stem cells. If validated, this mechanism would present a challenging target for medical intervention. PMID- 24228928 TI - Telomere biology: cancer firewall or aging clock? AB - It has been a decade since the first surprising discovery that longer telomeres in humans are statistically associated with longer life expectancies. Since then, it has been firmly established that telomere shortening imposes an individual fitness cost in a number of mammalian species, including humans. But telomere shortening is easily avoided by application of telomerase, an enzyme which is coded into nearly every eukaryotic genome, but whose expression is suppressed most of the time. This raises the question how the sequestration of telomerase might have evolved. The predominant assumption is that in higher organisms, shortening telomeres provide a firewall against tumor growth. A more straightforward interpretation is that telomere attrition provides an aging clock, reliably programming lifespans. The latter hypothesis is routinely rejected by most biologists because the benefit of programmed lifespan applies only to the community, and in fact the individual pays a substantial fitness cost. There is a long-standing skepticism that the concept of fitness can be applied on a communal level, and of group selection in general. But the cancer hypothesis is problematic as well. Animal studies indicate that there is a net fitness cost in sequestration of telomerase, even when cancer risk is lowered. The hypothesis of protection against cancer has never been tested in animals that actually limit telomerase expression, but only in mice, whose lifespans are not telomerase-limited. And human medical evidence suggests a net aggravation of cancer risk from the sequestration of telomerase, because cells with short telomeres are at high risk of neoplastic transformation, and they also secrete cytokines that exacerbate inflammation globally. The aging clock hypothesis fits well with what is known about ancestral origins of telomerase sequestration, and the prejudices concerning group selection are without merit. If telomeres are an aging clock, then telomerase makes an attractive target for medical technologies that seek to expand the human life- and health-spans. PMID- 24228929 TI - Studies that shed new light on aging. AB - I will first discuss how all aging models that assume that the aged cell has irreversibly lost its youthful capabilities through such mechanisms as accumulated dysfunction, accumulated damage, and/or accumulation of toxic byproducts of metabolism have been shown to be incorrect. I will then briefly discuss models of aging and propose an experiment that would distinguish between those models and provide a basis for organismic rejuvenation. PMID- 24228930 TI - High spatial and temporal resolution retrospective cine cardiovascular magnetic resonance from shortened free breathing real-time acquisitions. AB - BACKGROUND: Cine cardiovascular magnetic resonance (CMR) is challenging in patients who cannot perform repeated breath holds. Real-time, free-breathing acquisition is an alternative, but image quality is typically inferior. There is a clinical need for techniques that achieve similar image quality to the segmented cine using a free breathing acquisition. Previously, high quality retrospectively gated cine images have been reconstructed from real-time acquisitions using parallel imaging and motion correction. These methods had limited clinical applicability due to lengthy acquisitions and volumetric measurements obtained with such methods have not previously been evaluated systematically. METHODS: This study introduces a new retrospective reconstruction scheme for real-time cine imaging which aims to shorten the required acquisition. A real-time acquisition of 16-20s per acquired slice was inputted into a retrospective cine reconstruction algorithm, which employed non-rigid registration to remove respiratory motion and SPIRiT non-linear reconstruction with temporal regularization to fill in missing data. The algorithm was used to reconstruct cine loops with high spatial (1.3-1.8 * 1.8-2.1 mm2) and temporal resolution (retrospectively gated, 30 cardiac phases, temporal resolution 34.3 +/ 9.1 ms). Validation was performed in 15 healthy volunteers using two different acquisition resolutions (256 * 144/192 * 128 matrix sizes). For each subject, 9 to 12 short axis and 3 long axis slices were imaged with both segmented and real time acquisitions. The retrospectively reconstructed real-time cine images were compared to a traditional segmented breath-held acquisition in terms of image quality scores. Image quality scoring was performed by two experts using a scale between 1 and 5 (poor to good). For every subject, LAX and three SAX slices were selected and reviewed in the random order. The reviewers were blinded to the reconstruction approach and acquisition protocols and scores were given to segmented and retrospective cine series. Volumetric measurements of cardiac function were also compared by manually tracing the myocardium for segmented and retrospective cines. RESULTS: Mean image quality scores were similar for short axis and long axis views for both tested resolutions. Short axis scores were 4.52/4.31 (high/low matrix sizes) for breath-hold vs. 4.54/4.56 for real-time (paired t-test, P = 0.756/0.011). Long axis scores were 4.09/4.37 vs. 3.99/4.29 (P = 0.475/0.463). Mean ejection fraction was 60.8/61.4 for breath-held acquisitions vs. 60.3/60.3 for real-time acquisitions (P = 0.439/0.093). No significant differences were seen in end-diastolic volume (P = 0.460/0.268) but there was a trend towards a small overestimation of end-systolic volume of 2.0/2.5 ml, which did not reach statistical significance (P = 0.052/0.083). CONCLUSIONS: Real-time free breathing CMR can be used to obtain high quality retrospectively gated cine images in 16-20s per slice. Volumetric measurements and image quality scores were similar in images from breath-held segmented and free breathing, real-time acquisitions. Further speedup of image reconstruction is still needed. PMID- 24228932 TI - Section 4. What the guidelines have missed: a general discussion of the faculty: highlights of the asthma summit 2009: beyond the guidelines. AB - The sessions during the 2 days of the Asthma Summit focused largely on some specific aspects of the current European and U.S. guidelines for managing asthma. By way of summary, the faculty addressed the question of what they thought the guidelines missed, starting with consideration of those aspects of their own practice management that they believed are not clearly discussed in current guidelines. PMID- 24228931 TI - Planetary imaging in powers of ten: a multiscale, multipurpose astrobiological imager. AB - Contextual, multiscale astrobiological imaging is necessary to discover, map, and image patchy microbial colonization in extreme environments on planetary surfaces. The large difference in scale--several orders of magnitude--between search environment and microorganisms or microbial communities represents a challenge, which to date no single imaging instrument is able to overcome. In support of future planetary reconnaissance missions, we introduce an adapter based imager, built from an off-the-shelf consumer digital camera, that offers scalable imaging ranging from macroscopic (meters per pixel) to microscopic (micrometers per pixel) imaging, that is, spanning at least 6 orders of magnitude. Magnification in digital cameras is governed by (1) the native resolution of the CCD/CMOS chip of the camera, (2) the distance between camera and object to be imaged (focal length), and (3) the built-in optical and digital zoom. Both telezoom and macro mode alone are usually insufficient for microscopic imaging. Therefore, the focal distance has to be shortened, and the native CCD resolution of the camera has to be increased to attain a microscopic imaging capability. Our adapter-based imager bridges the gap between macroscopic and microscopic imaging, thereby enabling for the first time contextual astrobiological imaging with the same instrument. Real-world applications for astrobiology and planetary geology are discussed, and proof-of-concept imagery taken with our prototype is presented. PMID- 24228933 TI - Managing HIV/hepatitis C co-infection in the era of direct acting antivirals. AB - Morbidity and mortality from co-morbid hepatitis C (HCV) infection in HIV co infected patients are increasing; hence, the management of hepatitis co-infection in HIV is now one of the most important clinical challenges. Therefore, the development of direct acting antivirals (DAAs) for treatment of HCV has been eagerly awaited to hopefully improve HCV treatment outcome in co-infected individuals. Indeed, the availability of the first HCV protease inhibitors (PI) boceprevir and telaprevir for HCV genotype 1 patients has changed the gold standard of treating hepatitis C allowing for substantially improved HCV cure rates under triple HCV-PI/pegylated interferon/ribavirin therapy. Moreover, numerous other new DAAs are currently being studied in co-infected patient populations, also exploring shorter treatment durations and interferon-free treatment approaches promising much easier and better tolerated treatment regimens in the near future. Nevertheless, numerous challenges remain, including choice of patients to treat, potential for drug-drug interactions and overlapping toxicities between HIV and HCV therapy. The dramatically improved rates of HCV cure under new triple therapy, however, warrant evaluation of these new treatment options for all co-infected patients. PMID- 24228934 TI - Excess weight and abdominal obesity in postmenopausal Brazilian women: a population-based study. AB - BACKGROUND: The menopause is associated with a tendency to gain weight. Several alterations in fat deposits occur, leading to changes in the distribution of body fat. There are strong indications that, in middle age, obesity is associated with increased mortality. This study set out to determine the factors associated with the prevalence of overweight and abdominal obesity in postmenopausal women in a population-based study in Brazil. METHODS: The sample included 456 women, aged 45 69 years, residing in the urban area of Maringa, Parana. Systematic sampling, with a probability proportional to the size of the census sector, was performed. Behavioral, economic, and sociodemographic data were collected, and body mass index (BMI) and waist circumference (WC) were determined. RESULTS: According to BMI criteria (>=25.0 kg/m2), 72.6% of the women were overweight, and according to WC (>=88 cm), 63.6% had abdominal obesity. Based on logistic regression analysis, the factors that were most closely associated with overweight were: having three or more children (odds ratio (OR): 1.78; 95% confidence interval (CI): 1.06 3.00); and not taking hormone replacement therapy (OR: 1.69; 95% CI: 1.06-2.63). The prevalence of abdominal obesity was positively associated with greater parity (OR: 1.34, 95% CI: 1.05-1.72) and age older than 65 years (OR: 1.50; 95% CI: 1.03 2.19). CONCLUSIONS: This study found that the prevalences of overweight and abdominal obesity were higher for postmenopausal women who had three or more children. Age over 65 years was also a risk factor for abdominal obesity and no use of hormonal replacement therapy was a risk factor for overweight. PMID- 24228935 TI - Reflecting on the methodological challenges of recruiting to a United Kingdom wide, multi-centre, randomised controlled trial in gynaecology outpatient settings. AB - BACKGROUND: Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. METHODS: Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. RESULTS: Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. CONCLUSIONS: Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35911035. PMID- 24228936 TI - Cobalt- and iron-catalyzed redox condensation of o-substituted nitrobenzenes with alkylamines: a step- and redox-economical synthesis of diazaheterocycles. AB - A wide variety of functionalized 2-aryl benzimidazoles can be prepared by a solvent-free cobalt- or iron-catalyzed redox condensation of 2-nitroanilines and benzylamines. The cascade including benzylamine oxidation, nitro reduction, condensation, and aromatization occurs without any added reducing or oxidizing agent. The method can be extended to other alkylamines as reducing components or 2-nitrobenzamides as oxidizing components when using an iron/sulfur catalyst to afford various diazaheterocycles. PMID- 24228937 TI - Single-cell enzyme-free dissociation of neurospheres using a microfluidic chip. AB - Obtaining single dissociated cells from neurospheres is difficult using nonenzymatic methods. In this paper we report the development of a microfluidic chip-based approach that utilizes flow and microstructures to dissociate neurospheres. We show that this microfluidic-chip-based neurosphere-dissociation method can generate high yields of single cells from dissociated neurospheres of mouse KT98 and DC115 cell models (passage number, 3-8; diameter range, 40-250 MUm): 90% and 95%, respectively. The microfluidic-chip-dissociated cells had high viabilities (80-85%) and the ability to regrow into neurospheres, demonstrating the applicability of this device to neurosphere assay applications. In addition, the dissociated cells retained their normal differentiation potentials, as shown by their capabilities to differentiate into three neural lineages (neurons, astroglia, and oligodendrocytes) when cultured in differentiation culture conditions. Since this microfluidic-chip-based method does not require the use of enzymatic reagents, the risk of contamination from exogenous substances could be reduced, making it an attractive tool for a wide range of applications where neurosphere dissociation is needed. PMID- 24228938 TI - Coupled dissolution and precipitation at the cerussite-phosphate solution interface: implications for immobilization of lead in soils. AB - In situ atomic force microscopy (AFM) has been used to study the interaction of phosphate-bearing solutions with cerussite, PbCO3, (010) surfaces. During the dissolution of cerussite we observed simultaneous growth of needle-shaped or spherical pyromorphite phases. This occurred at two different pH values and ionic strengths relevant to soil solution conditions. The initial dissolution processes occurring at the cerussite solid-phosphate solution interface were clearly distinguished, and heterogeneous nucleation and growth rates of pyromorphites at phosphate concentrations ranging from 0.1 MUM to 10 mM were quantitatively defined. Enhanced cerussite dissolution in the presence of high salt (NaCl or NaF) concentrations leads to an increase in pyromorphite nucleation and growth rates. The newly formed pyromorphites were found to be stable upon contact with water or citrate-bearing solutions under acidic or alkaline conditions in the pH range 4-8. These in situ observations may improve the mechanistic understanding of processes resulting in lead immobilization in diverse soil systems as well as to enhance the effectiveness of phosphate-based treatments for remediation of lead-polluted soils. PMID- 24228939 TI - Water dynamics in aqueous solutions of tetra-n-alkylammonium salts: hydrophobic and Coulomb interactions disentangled. AB - We studied the effects of tetra-n-alkylammonium bromide (N(C(n)H(2n+1))(4)(+)Br( )) salts on the dynamics of water using polarization-resolved femtosecond infrared spectroscopy. With this technique, we are capable of distinguishing the response of water solvating the hydrophobic cations from that of water solvating the bromide anion. We observe that both types of ions slow down the orientational dynamics of the water molecules in their solvation shells. However, the nature of this slowdown is different for both ions. For the hydrophobic cation, we find an increasing number of retarded water molecules, scaling with the alkyl chain length. Water in the bromide solvation shell experiences a partial decay of its orientation by a fast wobbling motion, after which the remaining anisotropy decays much slower. The dynamics of the wobbling motion are observed to be dependent on the nature of the cation. For Me(4)NBr, the slow reorientation time is not concentration-dependent, and no aggregation is observed. This is in contrast to the tetra-n-alkylammonium salts with longer alkyl chains, for which the slow reorientation time of bromide-bound water molecules increases dramatically with concentration, and clusters of cations and anions appear to be formed. PMID- 24228940 TI - Diagnostic heterogeneity in psychiatry: towards an empirical solution. AB - The launch of the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has sparked a debate about the current approach to psychiatric classification. The most basic and enduring problem of the DSM is that its classifications are heterogeneous clinical descriptions rather than valid diagnoses, which hampers scientific progress. Therefore, more homogeneous evidence-based diagnostic entities should be developed. To this end, data-driven techniques, such as latent class- and factor analyses, have already been widely applied. However, these techniques are insufficient to account for all relevant levels of heterogeneity, among real-life individuals. There is heterogeneity across persons (p:for example, subgroups), across symptoms (s:for example, symptom dimensions) and over time (t:for example, course-trajectories) and these cannot be regarded separately. Psychiatry should upgrade to techniques that can analyze multi-mode (p-by-s-by-t) data and can incorporate all of these levels at the same time to identify optimal homogeneous subgroups (for example, groups with similar profiles/connectivity of symptomatology and similar course). For these purposes, Multimode Principal Component Analysis and (Mixture)-Graphical Modeling may be promising techniques. PMID- 24228942 TI - Catalytic reactions of acetylene: a feedstock for the chemical industry revisited. PMID- 24228941 TI - Ethnic and socio-economic disparities in oral health outcomes and quality of life among Sri Lankan preschoolers: a cross-sectional study. AB - INTRODUCTION: The distribution and severity of dental caries among preschool children vary according to the socio-economic and ethnic differences within and between countries. Understanding socio-economic influences on child oral health could inform early interventions to reduce the oral health burden throughout the life-cycle. The aim of this study is to examine the socio-economic and ethnic influences on oral health among preschoolers in Kegalle, Sri Lanka. METHODS: The study involved 784 children aged between 48-72 months recruited from 84 pre schools in the Kegalle district in Sri Lanka. Cross-sectional data were collected by means of an oral examination of the children and a self-administered questionnaire to their parents/caregivers. The Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess Oral Health related Quality of Life (OHQoL). Univariate and multivariate models of Poisson regression were used to investigate the associations between the variables. RESULTS: Compared to children whose fathers had tertiary education, those whose fathers did not study beyond grade 5, had more caries measured in terms of decayed, missing and filled surfaces (dmfs) (IRR = 2.30; 95% CI: 1.30, 4.06; p < 0.01) and experienced poor OHQoL at child (IRR = 2.52; 95% CI: 1.20, 5.31; p < 0.05) and family (IRR = 1.59; 95% CI: 1.11, 2.27; p < 0.05) levels. However, lower educational attainment among mothers was associated with better OHQoL among children. Compared to the Sinhalese ethnic group, Tamils had more gingival bleeding (bleeding surfaces) (IRR = 3.04; 95% CI: 1.92, 4.81; p < 0.001) and poor OHQoL at child level (IRR = 2.07; 95% CI: 1.19, 3.60; p < 0.01), whereas Muslims had poor OHQoL at family level (IRR = 1.42; 95% CI: 1.10, 1.84; p < 0.01). Children of low-income families had more gum bleeding (IRR = 1.00; 95% CI: 0.99, 1.00; p < 0.05) compared to children of high-income families. CONCLUSIONS: Socio-economic and ethnic differences in oral health outcomes exist among this population of preschoolers. Interventions targeting children of fathers with low educational levels and ethnic minority groups are required to reduce inequalities in oral health in Sri Lanka and other similar countries. PMID- 24228943 TI - Electrophysiological and behavioral responses of the whitestriped longhorned beetle, Batocera lineolata, to the diurnal rhythm of host plant volatiles of holly, Viburnum awabuki. AB - The adsorption method of Tenax-TA absorbent with GC-MS was used to analyze diurnal rhythms of volatiles from undamaged holly plants, Viburnum awabuki Kock (Dipsacales: Adoxaceae) holly infested by the white-striped longhorned beetle, Batocera lineolata Chevrolat (Coleoptera: Cerambycidae). Electroantennography and a Y-tube olfactometer were used to compare and analyze electroantennogram and behavioral responses of unmated male and female adults to the volatiles from V. awabuki (both undamaged and infested plants). The results of the GC-MS analysis showed that phytosterol and alkane are major volatiles for V. awabuki. The relative content of V. awabuki volatiles changed during the day. Electroantennogram and behavioral responses of unmated male and female adults to the volatiles from both undamaged and infested plants of V. awabuki were stronger between 08:00 and 10:00 and 16:00 and 18:00, which is consistent with early morning and evening feeding behaviors of adults in the field. PMID- 24228944 TI - Molecularly engineered surfaces for cell biology: from static to dynamic surfaces. AB - Surfaces with a well-defined presentation of ligands for receptors on the cell membrane can serve as models of the extracellular matrix for studying cell adhesion or as model cell surfaces for exploring cell-cell contacts. Because such surfaces can provide exquisite control over, for example, the density of these ligands or when the ligands are presented to the cell, they provide a very precise strategy for understanding the mechanisms by which cells respond to external adhesive cues. In the present feature article, we present an overview of the basic biology of cell adhesion before discussing surfaces that have a static presentation of immobile ligands. We outline the biological information that such surfaces have given us, before progressing to recently developed switchable surfaces and surfaces that mimic the lipid bilayer, having adhesive ligands that can move around the membrane and be remodeled by the cell. Finally, the feature article closes with some of the biological information that these new types of surfaces could provide. PMID- 24228945 TI - Pre-hypertension in Uganda: a cross-sectional study. AB - BACKGROUND: Persons with a systolic blood pressure (BP) of 120 to < 140 or diastolic BP of 80 to < 90 mm hg are classified as having pre-hypertension. Pre hypertension is associated with cardiovascular disease (CVD) risk factors, incident CVD and CVD mortality. Understanding determinants of pre-hypertension especially in low income countries is a pre-requisite for improved prevention and control. METHODS: Data were analyzed for 4142 persons aged 18 years and older with BP measured in a community cross sectional survey in Uganda. The prevalence of pre-hypertension was estimated and a number of risk factors e.g. smoking, use of alcohol, overweight, obesity, physical activity, sex, age, marital status, place of residence, and consumption of vegetables and fruits were compared among different groups (normotension, pre-hypertension, and hypertension) using bivariate and multivariable logistic regression. RESULTS: The age standardized prevalence of normal blood pressure was 37.6%, pre-hypertension 33.9%, hypertension 28.5% and raised blood pressure 62%. There was no difference between the prevalence of hypertension among women compared to men (28.9% versus 27.9%). However, the prevalence of pre-hypertension was higher among men (41.6%) compared to women (29.4%). Compared to people with normal blood pressure, the risk of pre hypertension was increased by being 40 years and above, smoking, consumption of alcohol, not being married, being male and being overweight or obese. Compared to pre-hypertension, hypertension was more likely if one was more than 40 years, had infrequent or no physical activity, resided in an urban area, and was obese or overweight. CONCLUSIONS: More than one in three of adults in this population had pre-hypertension. Preventive and public health interventions that reduce the prevalence of raised blood pressure need to be implemented. PMID- 24228947 TI - Editorial introduction: Sexuality, intimacy and counselling: perspectives from Africa. PMID- 24228949 TI - PREVALENCE OF Pharurus pallasii IN THE BELUGA WHALE ( Delphinapterus leucas ) OF CHURCHILL RIVER BASIN, MANITOBA. AB - Eight of 9 beluga whale ( Delphinapterus leucas ) in the Churchill River Basin were infected with Pharurus pallasii . The age range of infected whales was from under 1 year to 30 years. All adult infected animals had a large number of parasites in the accessory sinus, together with variable degrees of pulmonary granulomatous response. Histopathologic examination of lung revealed little host response to adult P. pallasii , but a strong inflammatory reaction to larval structures. Within the head, P. pallasii were found in the accessory sinus, ear canal and cerebral spinal fluid. PMID- 24228948 TI - Mirtazapine overdose is unlikely to cause major toxicity. AB - OBJECTIVE: There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. METHODS: This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. RESULTS: From 267 mirtazapine overdoses, there were 89 single agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26-49 years; Range: 15-81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270-750 mg; Range: 150-1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80-120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8-18.2 h; Range:2.2-75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co ingestants had more severe toxicity depending on the co-ingested drug. CONCLUSION: Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention. PMID- 24228950 TI - INTRACEREBRAL HEMORRHAGE IN A BOTTLENOSED DOLPHIN ( Tursiops truncatus ). AB - A neurologic condition closely resembling a common human disease, hypertensive intracerebral hemorrhage, is described in a captive dolphin. Motor deficits and the possibiltiy that behavioral changes resulted in the animal's being attacked and driven off by its herdmates, are discussed in terms of damage resulting from the hemorrhagic lesion. PMID- 24228952 TI - Haematozoan parasites of mourning doves in Florida. AB - A total of 918 mourning doves ( Zenaida macroura ) collected from six localities in Florida over a three year period (1973-1976) was examined for haematozoan infections. Three species of haematozoans were encountered: Haemoproteus maccallumi (92% prevalence), H. sacharovi (3% prevalence), and Leucocytozoon marchouxi (0.1% prevalence). No trypanosome or Plasmodium infections were found. Adult doves did not show sexually or seasonally-related differences in infection intensity. Immature doves, however, had parasitemias which showed cyclic seasonal fluctuations, but since these decreased with age, this seasonal fluctuation was interpreted to be due to changes in age composition of the population and not season itself. Doves from northern Florida showed significantly lower parasitemias than doves from the southern part of the state. PMID- 24228951 TI - Vaginal calculi in the dolphin. AB - Examination of the reproductive tract of a mature spotted dolphin, Stenella attenuata , revealed 13 vaginal calculi, composed primarily of calcium phosphate compounds. Vaginal calculi also were found in two mature Lagenorhynchus obliquidens and in six mature Delphinus delphis . PMID- 24228953 TI - SURVEY FOR Sarcocystis IN THE BROWN-HEADED COWBIRD ( Molothrus ater): A COMPARISON OF MACROSCOPIC, MICROSCOPIC AND DIGESTION TECHNIQUES. AB - Adult cowbirds from the Houston, Texas area were examined for Sarcocystis by three methods. Macroscopically, 53 of 253 (20.9%) birds examined were positive. Microscopic examination of abdominal muscle from 62 of the 200 negative birds showed another 4 (6.4%) to be infected. Pepsin digestion, the most sensitive technique for macroscopically negative birds, showed 7 of the 62 (11.2%) to be infected. PMID- 24228954 TI - Mandibular lesions of prehistoric aleutian sea mammals. AB - Disarticulated mandibles from prehistoric Aleutian sea mammals showed three general categories of paleopathology: (1) lesions imposed on the dentition and surrounding bone by bacteria and their by-products observed in 13 of 49, (2) lesions associated with periodontal disease observed in 14 of 49, and (3) lesions associated with mechanical attrition in 6 of 49. The sea mammal bones obtained from prehistoric eastern Aleutian village refuse middens suggest that younger and possibly weakened or old animals were preferentially captured by the Aleuts, although it remains to be determined the actual proportion of young to old, and the proportion of sick to healthy, in the natural populations. Radiography may be useful to determine the extent of dento-alveolar abscesses and periodontal disease in the absence of soft tissues for examination. PMID- 24228955 TI - Naturally occurring rabies virus and neutralizing antibody in two species of insectivorous bats of new york state. AB - Seven colonies of Eptesicus fuscus , the big brown bat, and five colonies of Myotis lucifugus , the little brown bat, in New York State were sampled for rabies virus and virus-neutralizing antibody. Eight of 278 E. fuscus were found to have virus, while 18 of 187 had antibody titers of >=1:8. One of 333 M. lucifugus yielded virus, while three of 127 had antibody. These data demonstrate the presence of rabies virus as well as immunity to rabies in some insectivorous bats of New York State. Evaluation of these findings in relation to the epizootiology of the disease in bats requires further investigation. PMID- 24228956 TI - Renal coccidiosis in wild ducks in Saskatchewan. AB - Ten of twelve species of wild ducks examined in central Saskatchewan were infected with renal coccidia. Of 261 ducks examined during autumn migration, 24.5% were infected while only 4% of 74 ducks examined during spring migration were infected. The greatest prevalence of infection occurred in female and juvenile birds. No gross lesions attributable to coccidia were found, and microscopic lesions were focal in nature. Oocysts from mallards were transmitted to captive mallards. PMID- 24228957 TI - Large scale mortality of nestling ardeids caused by nematode infection. AB - During the summer of 1976, an epornitic of verminous peritonitis caused by Eustrongylides ignotus resulted in large scale mortality of young herons and egrets on Pea Patch Island, Delaware. Mortality was highest (84%) in snowy egret nestlings ( Egretta thula ) and less severe in great egrets ( Casmerodius albus ), Louisiana herons ( Hydranassa tricolor ), little blue herons ( Florida caerulea ), and black crowned night herons ( Nycticorax nycticorax ). Most deaths occured within the first 4 weeks after hatching. Migration of E. ignotus resulted in multiple perforations of the visceral organs, escape of intestinal contents into the body cavity and subsequent bacterial peritonitis. Killifish ( Fundulus heteroclitus ) served as the source of infective larvae. PMID- 24228958 TI - Natural and experimental arboviral infections in a population of blacktail jackrabbits along the sacramento river in butte county, california (1971-1974). AB - A serologic survey of the blacktail jackrabbit ( Lepus californicus ) for infections with 10 arboviruses was conducted from 1971 through 1974 along the Sacramento River in Butte County, California. Of 325 animals captured and bled a total of 493 times, 40% were found positive for hemagglutination-inhibiting (HI) antibody to California encephalitis (CE) virus, 34% to western equine encephalomyelitis (WEE) virus, 20% to Buttonwillow virus, 15% to St. Louis encephalitis (SLE) virus and 12% to Main Drain virus. Only 5 and 2% of the animals had HI antibodies to Lokern and Turlock (TUR) viruses, respectively. There was no serologic evidence for infection of animals with Powassan, Modoc and Rio Bravo viruses. Differenles in monthly and yearly activities of some viruses were found by analyses of lata on antibody prevalence rates and immunologic conversions in recaptured animals. Experimental studies revealed that subadult jackrabbits were highly susceptible by subcutaneous inoculation to infection with CE, WEE and SLE viruses but were refractory to infection with TUR virus. All animals infected with CE and WEE viruses developed viremia that persisted for 2 or 3 days after inoculation and then developed antibodies that were detectable from 7 through at least 56 days after infection. In contrast, only 2 of 7 animals that developed HI antibodies to SLE virus had viremia, and at barely detectable levels; and HI antibodies were undetectable in 3 of the 7 animals at 56 days after infection. PMID- 24228959 TI - A survey of tularemia in wild mammals from fennoscandia. AB - A total of 2696 wild mammals from Fennoscandia were surveyed for tularemia. Francisella tularensis was not detected in livers/spleens or kidneys from any of the 1992 small rodents captured in Norway and Denmark as judged by one or more of the following methods: cultivation, immunofluorescence microscopy and inoculation in laboratory mice. Serologic examination of 704 wild mammals from Norway, Finland and Sweden demonstrated 11 cases of antibody titers. Agglutinating antibodies were demonstrated in 2 of 565 small rodents (titer 1:160), 2 of 26 wild rabbits (titer 1:80) and in 7 of 60 red deer (titer 1:20-1:40). The titers in red deer were low and could be due to cross reactions. No agglutinating antibodies were demonstrated in the sera of 53 domestic reindeer. PMID- 24228960 TI - Prevalence of nasal bots (Diptera: oestridae) in some zambian hartebeest. AB - Nine Lichtenstein's hartebeest ( Alcelaphus lichtensteini ) were sampled for nasal bots ( Oestrinae ) in a woodland area of central western Zambia. Larvae of the genera Gedoelstia , Oestrus and Kirkioestrus were found in mixed infestations in the nasal cavities and paranasal sinuses. A maximum count of 252 larvae was recorded from one head but no obvious pathogenicity was detectable in this or any other hartebeest. The significance of these findings is discussed in relation to the host specificity of the nasal bots and to gedoelstial myiasis of domestic livestock in the area where they interact with infected hartebeest. PMID- 24228961 TI - Serologic examination of wild birds for hemorrhagic enteritis of Turkey and marble spleen disease of pheasants. AB - Precipitin antibody which reacted with the hemorrhagic enteritis (HE) of turkeys/marble spleen disease (MSD) of pheasants group of avian adenoviruses, was not detected in serum samples of 618 wild birds (42 species) from Florida, Texas and Virginia. HE/MSD precipitin antibody was detected in serum samples of pen reared ring-necked pheasants ( Phasianus colchicus ) which had experienced MSD, but not in serum samples of similar MSD unaffected birds. PMID- 24228962 TI - HELMINTHS FROM WILLOW GROUSE ( Lagopus lagopus ) IN TWO LOCALITIES IN NORTH NORWAY. AB - A total of 77 adult and 123 juvenile willow grouse ( Lagopus lagopus ) from the island of Karlsoy, and 75 adult and 63 juvenile willow grouse from Sennaland on the mainland of North Norway were examined for helminths. Raillietina urogalli and Hymenolepis microps , and Ascaridia compar and Syngamus trachea were found. All four species occurred regularly in grouse from Karlsoy between April and September-October, but only H. microps was frequently found in birds from Sennaland. S. trachea only parasitised juvenile grouse. PMID- 24228963 TI - Hematozoa in sage grouse from colorado. AB - Blood films from 361 sage grouse ( Centrocercus urophasianus ) from North Park, Colorado, were examined for hematozoa. Parasites found were: Plasmodium pedioecetii , Haemoproteus canachites , Leucocytozoon bonasae , Trypanosoma avium , and microfilariae. The sage grouse represents a new host record for Plasmodium . Prevalence of parasitism was not age or sex related, with no significant (P > 0.05) differences between age or sex class. Parasite burdens increased significantly (P < 0.05) from January through May. As these burdens rose prior to the emergence of potential vectors, probably it was a true relapse associated with the resumption of the hosts' sexual activity. PMID- 24228964 TI - ATTEMPTS AT INFECTING RINGED TURTLE DOVES WITH VIRULENT Trichomonas gallinae. AB - Twenty Trichomonas -free ringed turtle doves ( Streptopelia risoria ) were inoculated per os with the highly virulent Jones' Barn strain of Trichomonas gallinae . None became infected. Three F1 females housed together were similarly inoculated with this strain and remained Trichomonas -positive for upwards of 182 days. They showed no disease and eventually lost their infections. These three positive females "mated" and laid several six-egg sets in a communal nest. At successive nestings they were given: 1) a fertile domestic pigeon ( Columba livia ) egg, and 2) two fertile ringed dove eggs, all of which hatched. The pigeon squab died of trichomoniasis on day four; the doves survived to maturity. When trichomonads from these doves were placed in Trichomonas -free domestic pigeons the latter all died of T. gallinae trichomoniasis on postinoculation day 8.1 (average). PMID- 24228965 TI - EXPERIMENTAL EXPOSURE OF FRANKLINS' GULLS ( Larvus pipixcan ) AND MALLARDS ( Anas platyrhynchos ) TO A TURKEY INFLUENZA A VIRUS A/Turkey/Minn/BF/72 (Hav6Neq2). AB - Gulls ( Larvus pipixcan ) and mallards ( Anas platyrhynchos ) were experimentally exposed to a turkey influenza A isolant, A/turkey/Minn/BF/72 (Hav6Neq 2). No clinical signs of disease were observed in either species. Tracheal shedding of virus from the gulls persisted for 24 days post-inoculation but virus later than 6 days post exposure could not be demonstrated in either tracheal or cloacal samples from the mallards. Precipitating antibodies were not detected. Hemagglutination-inhibition antibodies were demonstrated in inoculated gulls but antibody levels were low and erratic in ducks. PMID- 24228966 TI - NOTES ON POPULATIONS OF Bovicola jellisoni ON DALL'S SHEEP ( Ovis dalli ). AB - This paper reports the first record of a mallophagan species on the Dall's sheep ( Ovis dalli ). The numbers and distribution of Bovicola jellisoni on two Dall's sheep collected on Crescent Mountain, Kenai Peninsula, Alasaka, is described. PMID- 24228967 TI - Survey of colorado's wild ruminants for serologic titers to brucellosis and leptospirosis. AB - A 10-year survey for serologic titers to brucellosis and leptospirosis in mule deer ( Odocoileus hemionus ), elk ( Cervus canadensis ), and antelope ( Antilocapra americana ) in Colorado is summarized. Over 10,000 blood samples were tested against Brucella abortus and 4,747 samples were tested against Leptospira pomona . A total of 1,761 blood samples were tested against L. canicola , L. grippotyphosa , L. hardjo , L. icterohemorrhagiae . All results were considered negative. PMID- 24228968 TI - Helminths of the black bear in quebec. AB - Twenty-one complete carcasses of black bears, Ursus americanus , together with 34 intestinal tracts, 86 diaphragms and 168 faecal droppings collected between June, 1971 and November, 1972 in the Province of Quebec were examinel for helminths. Species found and their prevalence were as follows: Dirofilaria ursi in 57%; Uncinaria yukonensis in 6%; Baylisascaris transfuga in 21%; larvae of Trichinella spiralis in less than 1%; Diphyllobothrium ursi in 36%; and Taenia krabbei and Taenia hydatigena in 4%. These findings are discussed in the light of other reports. PMID- 24228969 TI - PARASITES OF WATERFOWL FROM SOUTHWEST TEXAS: II. THE SHOVELER, Anas clypeata. AB - Thirty-eight shoveler ducks, Anas clypeata , were collected in the Rio Grande Valley, Hudspeth County, Texas. Nineteen species of helminths, six species of lice and a sarcosporidian, Sarcocystis rileyi , were recorded. Seventeen of the nineteen species of helminths were observed in fall migrants and twelve species were recorded from spring migrants. The nematode Alifilaria pochardi Ali, 1969, is a new host and American record. PMID- 24228970 TI - Cerebrospinal parelaphostrongylosis in fallow deer. AB - Neurologic disease attributed to infection by meningeal worm ( Parela phostrongylus tenuis ) was diagnosed in seven fallow deer ( Dama dama ) from the Land Between The Lakes region of Kentucky. Afflicted deer had paresis or paralysis of the hindquarters which quickly progressed to tetraplegia. Gross and microscopic cerebrospinal lesions were similar to those previously reported and consisted mainly of nonsuppurative meningitis and radiculitis, focal granulomas on the surface of the spinal cord, and nonselective malacia and glial scarring in brain and spinal cord. Living P. tenuis were recovered from brain or spinal cord in two deer, and degenerating nematodes were found in four. Possible epizootiologic relationships between the parasite, fallow deer and white-tailed deer ( Odocoileus virginianus ) are discussed. PMID- 24228971 TI - EXPERIMENTAL INFECTION OF COLLARED PECCARY ( Dicotyles tajacu angulatus ) WITH SWINE KIDNEY WORM ( Stephanurus dentatus ). AB - Two captive-born juvenile collared peccaries ( Dicotyles tajacu angulatus ) were given 3000 infective larvae of Stephanurus dentatus per os. One peccary harbored viable S. dentatus sub-adults in the liver 50 days post-infection. The other peccary had no larvae but did have diffuse fibrotic hepatic lesions and bile duct hyperplasia 213 days post-infection; however, the lesions may have been partially due to a concurrent Ascaris suum infection. A domestic pig ( Sus scrofa domesticus ) infected as a control was severely but non-patently parasitized 170 days postinfection. PMID- 24228972 TI - Calicivirus antibodies in wild fox populations. AB - Three populations of wild foxes were sampled for serum neutralizing antibody to calicivirus (San Miguel sea lion virus) types 1-5. Neutralizing activity was detected in serum from gray foxes resident on Santa Cruz Island, California, but not in Arctic foxes from Alaska. The results indicate that foxes may be naturally infected with caliciviruses, but their role in the transmission cycle is unknown. PMID- 24228974 TI - Public service quality improvements: a case for exemption from IRB review of public administration research. AB - Should the exemption from Institutional Review Board (IRB) evaluations currently in place for quality improvements research be extended to public administration research that addresses questions of improving the quality of public service delivery? As a means to both reduce the level of disdain held by a group of social science researchers for IRBs and to reduce the cost of review for minimal risk studies, I argue here that much of the current public administration research should also be exempted from normal processes of review by IRBs on the basis of their similarity to Quality Improvements (QI) research, a category of studies already granted exemption. This argument dovetails provisions currently in place for studies of public service and public benefit, but reframes these exemptions in the language of "quality improvements," which may be a more comfortable language for IRBs concerned to demonstrate compliance for review of all fields. To expedite this argument into the practices of IRBs, I included a checklist that researchers could use to self-identify their studies as QI, not research as such. PMID- 24228975 TI - A core-item reviewer evaluation (CoRE) system for manuscript peer review. AB - Manuscript peer review is essential for ensuring accountability to all involved in the publication process, including authors, journals, and readers. Lack of consensus regarding what constitutes an accountable manuscript peer review process has resulted in varying practices from one journal to the next. Currently, reviewers are asked to make global judgments about various aspects of a paper for review irrespective of whether guided by a review checklist or not, and several studies have documented gross disagreement between reviewers of the same manuscript. We have previously proposed that the solution may be to direct reviewers to concrete items that do not require global judgments but rather provide a specific choice, along with referee justification for such choices. This study evaluated use of such a system via an international survey of health care professionals who had recently reviewed a health care--related manuscript. Results suggest that use of such a peer review system by reviewers does indeed improve interreviewer agreement, and thus, has the potential to support more consistent and effective peer review, if introduced into journal processes for peer review. PMID- 24228976 TI - Fostering integrity in postgraduate research: an evidence-based policy and support framework. AB - Postgraduate research students have a unique position in the debate on integrity in research as students and novice researchers. To assess how far policies for integrity in postgraduate research meet the needs of students as "research trainees," we reviewed online policies for integrity in postgraduate research at nine particular Australian universities against the Australian Code for Responsible Conduct of Research (the Code) and the five core elements of exemplary academic integrity policy identified by Bretag et al. (2011 ), i.e., access, approach, responsibility, detail, and support. We found inconsistency with the Code in the definition of research misconduct and a lack of adequate detail and support. Based on our analysis, previous research, and the literature, we propose a framework for policy and support for postgraduate research that encompasses a consistent and educative approach to integrity maintained across the university at all levels of scholarship and for all stakeholders. PMID- 24228977 TI - Commentary: peer review and incomplete reference lists. PMID- 24228978 TI - Myogenic bladder defects in mouse models of human oculodentodigital dysplasia. AB - To date, over 65 mutations in the gene encoding Cx43 (connexin43) have been linked to the autosomal-dominant disease ODDD (oculodentodigital dysplasia). A subset of these patients experience bladder incontinence which could be due to underlying neurogenic deterioration or aberrant myogenic regulation. BSMCs (bladder smooth muscle cells) from wild-type and two Cx43 mutant lines (Cx43(G60S) and Cx43(I130T)) that mimic ODDD exhibit a significant reduction in total Cx43. Dye transfer studies revealed that the G60S mutant was a potent dominant-negative inhibitor of co-expressed Cx43, a property not equally shared by the I130T mutant. BSMCs from both mutant mouse strains were defective in their ability to contract, which is indicative of phenotype changes due to harbouring the Cx43 mutants. Upon stretching, Cx43 levels were significantly elevated in controls and mutants containing BSMCs, but the non-muscle myosin heavy chain A levels were only reduced in cells from control mice. Although the Cx43(G60S) mutant mice showed no difference in voided urine volume or frequency, the Cx43(I130T) mice voided less frequently. Thus, similar to the diversity of morbidities seen in ODDD patients, genetically modified mice also display mutation-specific changes in bladder function. Furthermore, although mutant mice have compromised smooth muscle contraction and response to stretch, overriding bladder defects in Cx43(I130T) mice are likely to be complemented by neurogenic changes. PMID- 24228979 TI - Cardiac steatosis and left ventricular function in men with metabolic syndrome. AB - BACKGROUND: Ectopic accumulation of fat accompanies visceral obesity with detrimental effects. Lipid oversupply to cardiomyocytes leads to cardiac steatosis, and in animal studies lipotoxicity has been associated with impaired left ventricular (LV) function. In humans, studies have yielded inconclusive results. The aim of the study was to evaluate the role of epicardial, pericardial and myocardial fat depots on LV structure and function in male subjects with metabolic syndrome (MetS). METHODS: A study population of 37 men with MetS and 38 men without MetS underwent cardiovascular magnetic resonance and proton magnetic spectroscopy at 1.5 T to assess LV function, epicardial and pericardial fat area and myocardial triglyceride (TG) content. RESULTS: All three fat deposits were greater in the MetS than in the control group (p <0.001). LV diastolic dysfunction was associated with MetS as measured by absolute (471 mL/s vs. 667 mL/s, p = 0.002) and normalized (3.37 s-1 vs. 3.75 s-1, p = 0.02) LV early diastolic peak filling rate and the ratio of early diastole (68% vs. 78%, p = 0.001). The amount of epicardial and pericardial fat correlated inversely with LV diastolic function. However, myocardial TG content was not independently associated with LV diastolic dysfunction. CONCLUSIONS: In MetS, accumulation of epicardial and pericardial fat is linked to the severity of structural and functional alterations of the heart. The role of increased intramyocardial TG in MetS is more complex and merits further study. PMID- 24228981 TI - Magnetic microrheology of block copolymer solutions. AB - The viscosity of poly(styrene)-b-poly(lactide) [PS-b-PLA] solutions in a neutral solvent was characterized by magnetic microrheology. The effect of polymer concentration on the viscosity of the block polymer solutions was compared with that of the PS and PLA homopolymers in the same solvent. The viscosity of PS-b PLA solution, unlike the homopolymer solutions, showed a steep increase over a narrow concentration range. The steep rise was concomitant with microphase separation into an ordered cylindrical microstructure as determined by small angle X-ray scattering. Hence microrheology proved effective as a means of characterizing the order-disorder transition concentration. During an in situ drying experiment, changes in local viscosity through the depth of a block copolymer solution were characterized as a function of drying time. Early in the drying process, the viscosity rose steadily and was uniform through the depth, a result consistent with steadily increasing and uniform polymer concentration. However, later in the drying process as the overall polymer concentration approached that required for microphase separation, the viscosity of the polymer solution near the free surface became an order of magnitude higher than that near the bottom of the container. The zone of high viscosity moved downward as drying proceeded, consistent with a microphase separation front. PMID- 24228980 TI - Definitions of and contributions to cardiovascular disease in systemic lupus erythematosus. AB - Patients with systemic lupus erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). Increased prevalence of atherosclerosis may explain part of this enhanced risk, but SLE related CVD can also result from other mechanisms. Vascular events may be the result of several pathophysiologic mechanisms; some can be caused by atherosclerosis, others may be primarily thrombotic, and some may be due to ongoing inflammation. The traditional risk factors are of importance for the development of CVD in lupus. However, lupus related factors, such as endothelial dysfunction and inflammation, renal impairment and disease activity, lupus phenotype, autoantibodies and genetic predisposition are equally or even more important. Risk factors may also contribute separately or in combination to increase the risk of atherosclerosis and clinical CVD in SLE. Studies investigating risk factors for CVD in SLE vary with respect to definition of outcome, it is, e.g. common that the terms atherosclerosis and clinical CVD are used interchangeably. Varying definitions and outcomes may thus explain divergent results of different studies and make comparisons difficult. This review summarizes some of the current knowledge regarding risk factors and mechanisms for atherosclerosis and clinical CVD in SLE. Aspects on the importance of CVD definitions and outcomes are briefly discussed. PMID- 24228982 TI - Characteristics of nonallergic vasomotor rhinitis. AB - Nonallergic rhinitis (NAR) conditions are currently considered diagnoses by exclusion. A diagnosis of NAR requires negative specific IgE responses by skin or serologic testing and more recently testing to exclude localized production of specific IgE in the nose. Symptoms are classically aggravated by irritant triggers such as tobacco smoke, perfumes/fragrances, and temperature or barometric pressure changes. A previously developed questionnaire survey designed to help physicians recognize differences between allergic rhinitis and nonallergic rhinitis subtypes found that patients with symptom onset later in life (> 35 years), no family history of allergies, no seasonality or cat-induced symptoms, and symptoms induced by perfumes and fragrances had > 95% likelihood of having a physician diagnosis of NAR. Of note, clinical symptoms were not generally useful for differentiating chronic rhinitis subtypes which has also been confirmed in a more recent study investigating the relationship between headaches and chronic rhinitis subtypes (Table 1). In subsequent studies it was found that a significant percentage of NAR patients did not experience irritant induced symptoms, suggesting that these triggers are not a clinical characteristic that can be uniformly used for all NAR patients. However, a newly developed Irritant Index Scale can be used to reliably differentiate pure allergic rhinitis from nonallergic rhinitis with trigger phenotypes. The use of standardized and validated questionnaires allows objective characterization of chronic rhinitis subtypes that appears to improve the accuracy of clinically diagnosing these patients. PMID- 24228983 TI - Pullulan-based nanoparticles: future therapeutic applications in transmucosal protein delivery. PMID- 24228984 TI - News & analysis. PMID- 24228985 TI - Industry Update: The latest developments in therapeutic delivery. AB - This article provides a snapshot of the news stories from the world of therapeutic delivery in the period 1-31 August 2013. During this month, the Boards of Amgen and Onyx Pharmaceuticals gave their approval to the purchase by Amgen of Onyx's outstanding shares in a deal worth US$10.4 billion, or $9.7 billion net of estimated Onyx cash. The deal, said to be the fifth largest involving a biotechnology company, is expected to close in Q4 2013 subject to customary closing conditions and regulatory approval. August also saw the publication of a reflection paper on the coating of nanomedicines by the European Medicines Agency's Committee for Medicinal Products for Human Use. This paper highlights the key considerations for the development of nanomedicine and nanosimilars (nanomedicines that are claimed to be similar to a reference nanomedicine) and makes recommendations with regard to the quality control and assurance of such products. As ever, the Industry Update is based mainly on information from press releases and company websites. PMID- 24228986 TI - Research Spotlight: Functionalized nanoparticles for future cardiovascular medicine. AB - All research investment has the goal of improving quality of life and health status. In recent years, the emerging technologies in nanomedicine research provide us a new frontier in the fight against human disease. By taking advantage of the unique physicochemical properties of nanoparticles (NPs), nanomedicine where drugs are blended into nanomaterials readily offers a wide range of applications in the tracing, diagnosis and treatment of disease. Although the application of therapeutic NPs is predominantly for cancer treatment, growing evidence has demonstrated the feasibility and potency of utilizing NPs for cardiovascular disease therapy. However, more consideration is required in this aspect due to limitations such as unfavorable particle retention in the contractile heart and the lack of cardiomyocyte markers for targeting. PMID- 24228987 TI - Gene therapy in the clinics: shifting into the next gear. PMID- 24228988 TI - Assessment of novel iloperidone- and idebenone-loaded nanostructured lipid carriers: brain targeting efficiency and neuroprotective potential. AB - BACKGROUND: To evaluate the outcome of combining iloperidone with idebenone in the form of brain-targeted nanostructured lipid carrier (NLC) on the expression of endogenous antioxidant enzymes present in the brain, and hence establish the neuroprotective activity. RESULTS: The combination NLC demonstrated good targeting potential (>85%) as compared with pure iloperidone (22.21%). The levels of various endogenous antioxidant enzymes present in the brain were reduced significantly (p < 0.001) in case of 28 days repeated administration of pure iloperidone, while administration of the combination NLC helped to restore the levels of these enzymes. CONCLUSION: Combining iloperidone with idebenone and converting into NLC has contributed in effectively reducing oxidative stress in the brain and helped in reversing the catalepsy induced by repeated iloperidone administration. PMID- 24228989 TI - Positively charged microemulsions of dexamethasone: comparative effects of two cosurfactants on ocular drug delivery and bioavailability. AB - BACKGROUND: The objective of this investigation was to evaluate the potential of mucoadhesive chitosan-coated positively charged microemulsions (CH-MEs) of dexamethasone with respect to the change in nonionic cosurfactants. METHODS: CH MEs were prepared with different concentrations of surfactant and cosurfactant using the water titration method and coated with low-molecular-weight chitosan. RESULTS: All formulations displayed an average globule size between 85 and 187 nm and a positive surface charge. The optimized CH-MEs showed greater penetration of dexamethasone in the anterior segment of the eye, resulting in twofold and fourfold higher dexamethasone concentration than uncoated ME and drug suspension, respectively. CONCLUSION: The developed CH-MEs shows increases in ocular penetration and bioavailability. PMID- 24228990 TI - Cellular therapeutics delivery to the spinal cord: technical considerations for clinical application. AB - Current literature demonstrates the efficacy of cell-based therapeutics in small animal models of varied spinal cord diseases. However, logistic challenges remain towards development of an optimized delivery approach to the human spinal cord. Clinical trials utilize a variety of methods to achieve this aim. In this article, the authors review currently employed delivery methods, compare the merits of alternate delivery paradigms, introduce their implementation in completed and ongoing clinical trials, and discuss promising near-term advances in image-guided delivery and in vivo graft tracking. PMID- 24228991 TI - Controlling the actuation of therapeutic nanomaterials: enabling nanoparticle mediated drug delivery. AB - The implementation of biofunctionalized nanoparticles (NPs) as potential therapeutic materials has seen exponential growth in recent years due to their unique ability to overcome the constraints of current medicine. This has been largely driven by significant advances on a number of basic research fronts including high-quality NP synthesis, bioconjugation, cellular delivery and the controlled release or 'actuation' of NP-associated cargos. Cumulatively, these are the key enabling tools for the full realization of NP-mediated drug delivery. In this review, the authors' focus is on recent developments in methodologies for the controlled actuation of therapeutic NPs. The authors discuss the critical requirements for their integration into biological systems and highlight examples from the recent literature where controlled NP actuation has been successfully demonstrated. The current state of therapeutic NPs in the clinical setting is summarized and the article concludes with a brief perspective of how we can expect to see this emerging field develop in the coming years. PMID- 24228992 TI - Block copolymer nanoassemblies for photodynamic therapy and diagnosis. AB - Light can be a powerful therapeutic and diagnostic tool. Light-sensitive molecules can be used to develop locally targeted cancer therapeutics. This approach is known as photodynamic therapy (PDT). Similarly, it is possible to diagnose diseases and track the course of treatment in vivo using ligh-sensitive molecules. This methodology is referred to as photodynamic diagnosis (PDD). Despite the potential, many PDT and PDD agents have imperfect physiochemical properties for their successful clinical application. Nanotechnology may solve these issues by improving the viability of PDT and PDD. This review summarizes the current state of PDT and PDD development, the integration of nanotechnology in the field, and the prospective future applications, demonstrating the potential of PDT and PDD for improved cancer treatment and diagnosis. PMID- 24228995 TI - Erratum. PMID- 24228996 TI - Two-component, three-molecule reactions between 2,3-dihydroinden-1-ones and aryl chlorides catalyzed by an N-heterocyclic carbene-palladium(II)-1-methylimidazole complex. AB - The two-component, three-molecule reactions between 2,3-dihydroinden-1-ones and aryl chlorides were achieved in the presence of an NHC-Pd(II)-Im complex. Under the optimal conditions, all reactions performed well to give the corresponding products in moderate to high yields. PMID- 24228997 TI - Equity in reproductive and maternal health services in Bangladesh. AB - BACKGROUND: The target date for achieving the Millennium Development Goals (MDGs) is now closer than ever. There is lack of sufficient progress in achieving the MDG targets in many low- and middle-income countries. Furthermore, there has also been concerns about wide spread inequity among those that are on track to achieve the health-related MDGs. Bangladesh has made a notable progress towards achieving the MDG 5 targets. It is, however, important to assess if this is an inclusive and equitable progress, as inequitable progress may not lead to sustainable health outcomes. The objective of this study is to assess the magnitude of inequities in reproductive and maternal health services in Bangladesh and propose relevant recommendations for decision making. METHODS: The 2007 Bangladesh demographic and health survey data is analyzed for inequities in selected maternal and reproductive health interventions using the slope and relative indices of inequality. RESULTS: The analysis indicates that there are significant wealth-related inequalities favouring the wealthiest of society in many of the indicators considered. Antenatal care (at least 4 visits), antenatal care by trained providers such as doctors and nurses, content of antenatal care, skilled birth attendance, delivery in health facility and delivery by caesarean section all manifest inequities against the least wealthy. There are no wealth-related inequalities in the use of modern contraception. In contrast, less desired interventions such as delivery by untrained providers and home delivery show wealth-related inequalities in favour of the poor. CONCLUSIONS: For an inclusive and sustainable improvement in maternal and reproductive health outcomes and achievement of MDG 5 targets, it essential to address inequities in maternal and reproductive health interventions. Under the government's stewardship, all stakeholders should accord priority to tackling wealth-related inequalities in maternal and reproductive health services by implementing equity-promoting measures both within and outside the health sector. PMID- 24228993 TI - Basics and recent advances in peptide and protein drug delivery. AB - While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site specific delivery are also discussed. PMID- 24228998 TI - Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children - a prospective observational cohort study of 6,601 admissions. AB - BACKGROUND: Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. METHODS: We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. RESULTS: A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). CONCLUSIONS: ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries. PMID- 24228999 TI - Antistaphylococcal and biofilm inhibitory activities of gallic, caffeic, and chlorogenic acids. AB - Staphylococcus aureus is a Gram-positive pathogen which is able to form biofilms, exhibiting a more pronounced resistance to antibiotics and disinfectants. The hurdles posed in eradicating biofilms have driven the search for new compounds able to fight these structures. Phenolic compounds constitute one of the most numerous and ubiquitous group of plant secondary metabolites with many biological activities. The aim of the present work was to study the potential antimicrobial and antibiofilm properties of gallic, caffeic, and chlorogenic acids against S. aureus as well to elucidate its mechanism of action. It was concluded that the phenolic acids studied in this work have antistaphylococcal properties. For instance, gallic acid is able to influence the adhesion properties of S. aureus. The phenolic acids tested were also able to inhibit the production of alpha hemolysin by this microorganism, with the exception of chlorogenic acid. Regarding its mechanism of action, caffeic acid interferes with the stability of the cell membrane and with the metabolic activity of the cells of S. aureus. PMID- 24229002 TI - In a disaster, social media has the power to save lives. PMID- 24229005 TI - Tailoring porosity in carbon nanospheres for lithium-sulfur battery cathodes. AB - Porous hollow carbon spheres with different tailored pore structures have been designed as conducting frameworks for lithium-sulfur battery cathode materials that exhibit stable cycling capacity. By deliberately creating shell porosity and utilizing the interior void volume of the carbon spheres, sufficient space for sulfur storage as well as electrolyte pathways is guaranteed. The effect of different approaches to develop shell porosity is examined and compared in this study. The most highly optimized sulfur-porous carbon nanosphere composite, created using pore-formers to tailor shell porosity, exhibits excellent cycling performance and rate capability. Sulfur is primarily confined in 4-5 nm mesopores in the carbon shell and inner lining of the shells, which is beneficial for enhancing charge transfer and accommodating volume expansion of sulfur during redox cycling. Little capacity degradation (~0.1% /cycle) is observed over 100 cycles for the optimized material. PMID- 24229006 TI - Embedded performance validity indicators within the California Verbal Learning Test, Children's Version. AB - To date, few studies have examined the use of embedded performance validity indicators in pediatric populations. The present study examined the utility of variables within the California Verbal Learning Test, Children's Version (CVLT-C) in detecting noncredible effort among a pediatric mild traumatic brain injury sample. The sample consisted of 411 clinically referred patients aged 8-16 years. A total of 13% of the participants failed both the Medical Symptom Validity Test and at least one other performance validity measure. No demographic or injury related variables differentiated the noncredible and adequate effort groups. The noncredible group performed significantly worse than the adequate effort group across a majority of CVLT-C variables. Logistic regression analysis revealed that the Recognition Discriminability (RD) score was the most robust in predicting noncredible effort. Among this relatively high-functioning sample, an RD cutoff z score of -0.5 resulted in sensitivity of 55% and specificity of 91%. A more conservative RD cutoff z-score of -1.0 resulted in sensitivity of 41% and specificity of 97%. These findings are comparable to the classification statistics found for many embedded indicators in the adult literature. Although only moderately sensitive, the RD score on the CVLT-C appears to have good utility in identifying noncredible effort in a relatively high-functioning pediatric mTBI population. PMID- 24229008 TI - Primary cerebral myxopapillary ependymoma presenting with intratumoral hemorrhage. AB - Myxopapillary ependymoma (MPE), a benign histological variant of ependymoma, is found most commonly in the cauda equina region. Primary intracranial MPE is very rare, and most cases are a metastatic deposit from a spinal lesion. Primary cerebral MPEs are usually well-defined solid or cystic lesions without hemorrhage. We report the first case of primary cerebral MPE with intratumoral hemorrhage. PMID- 24229007 TI - DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions. AB - The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders. PMID- 24229009 TI - New criteria to predict tumor recurrence in invasive ductal carcinoma of the breast. AB - Incidence of triple-negative breast cancer (TNBC), which is cancer without expression of ER, PgR, and HER2, and nuclear grade (NG) are closely correlated with malignant potential of breast cancer. However, criteria to determine aggressiveness of breast cancer based on these factors have not been elucidated. The aim of this study was to create criteria using these factors to predict tumor recurrence in invasive ductal carcinoma (IDC) of the breast. One hundred and seventy-nine patients with IDC of the breast, which had been treated by surgical resection, were included. One point was added for each factor of the two categories of TNBC and NG 3. The sum of the scores (TGS 0, 1, or 2) was calculated. Significant difference was observed between TGS and the incidence of tumor recurrence (P < 0.0001). Moreover, significant differences were observed regarding relapse-free survival (RFS) between patients with TGS 0 and TGS 1 (P < 0.0001) and patients with TGS 1 and TGS 2 (P = 0.024). TGS might contain a clinical advantage as a useful predictor for tumor recurrence of IDC of the breast and could classify prognosis of the patients with a preferable stratification. PMID- 24229010 TI - Syndrome of inappropriate secretion of antidiuretic hormone due to selective serotonin reuptake inhibitors after pancreaticoduodenectomy for carcinoma of the ampulla of Vater: case report. AB - A 68-year-old man underwent pancreaticoduodenectomy with lymph nodes dissection for carcinoma of the ampulla of Vater. The patient had anxiety neurosis and had been treated with a selective serotonin reuptake inhibitor (SSRI). Postoperatively, SSRI was resumed on postoperative day 2. His serum sodium concentration gradually decreased, and the patient was given a sodium supplement. However, 11 days after the operation, laboratory findings included serum sodium concentration of 117 mEq/L, serum vasopressin of 2.0 pg/mL, plasma osmolality of 238 mOsm/kg, urine osmolality of 645 mOsm/kg, urine sodium concentration of 66 mEq/L, serum creatinine concentration of 0.54 mg/dL, and serum cortisol concentration of 29.1 MUg/dL. With a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH), the antianxiety neurosis medication was changed from the SSRI to another type of drug. After switching the medication, the patient made a satisfactory recovery with normalization of serum sodium by postoperative day 20. PMID- 24229011 TI - Surgical stress response after colorectal resection. AB - The human body's response to surgery is correlated with the extent of tissue damage. The aim of the present study was to, over time, map out parameters concerning inflammation, metabolism, nutrition, breathing function, muscle strength, and well-being in elective colorectal surgery. Eighteen patients were prospectively included: colon resection (n = 9) and rectum resection/amputation (n = 9). Postoperative interleukin 10 (IL-10) rose more in the rectum surgery group on day 0 (P = 0.007) and day 3 (P = 0.025). Furthermore, significant differences between groups were detected regarding albumin, prealbumin, and total iron-binding capacity (TIBC). For albumin and TIBC, this difference was seen even on day 7. C-reactive protein, IL-6, IL-8, glucose, cortisol, insulin, pain, fatigue, nausea, grip strength, and forced expiratory volume in 1 second did not show any differences. No correlation was revealed between measured parameters and postoperative complications. Postoperative levels of IL-10, albumin, prealbumin, and TIBC may be used as determinants of surgical stress after colorectal surgery. PMID- 24229012 TI - Is ostomy still mandatory in rectal injuries? AB - The aim of this study was to compare the outcomes of the treatment methods of ostomy and primary repair in rectal injuries. A total of 63 patients with rectal injury who had been treated at Dicle University Hospital between 2000 and 2011 were retrospectively reviewed. To determine the outcomes of the treatment methods, the patients were divided into 2 groups (ostomy group: patients who underwent ostomy plus primary repair; repair group: patients who only underwent primary repair) and compared. The patients included 51 men and 12 women. A total of 44 patients underwent ostomy, whereas 19 patients underwent primary repair. No morbidity was detected in either group with grade II intraperitoneal rectal injury. The outcomes of the patients with grade II intraperitoneal and extraperitoneal rectal injury were similar. In the treatment of patients with low grade rectal injuries, primary repair can be preferred to ostomy. PMID- 24229013 TI - A new technique in management of pilonidal sinus, a university teaching hospital experience. AB - This paper evaluates a new technique that can lead to excision of pilonidal sinus with less healing time and low recurrence rate. A prospective randomized double blind controlled study on 142 patients with pilonidal sinus conducted during the period from September 2008 to March 2012. The patients were prospectively randomized to be operated with one of four surgical techniques, excision and primary closure, or excision after using hydrogen peroxide (H202) and primary closure, or excision without closure, or excision after injection of H202 without closure. The main outcome measures were the healing time and the recurrence rate. Out of 142 patients, 118 patients were males (83%), and 24 were females (17%). The mean age was 24.5 years. The recurrence rate in patients treated with excision after injection of H202 without closure was the lowest (1.8%) with P value < 0.005, and the mean duration of healing was 30.7 days with P-value < 0.005. We recommend using excision after injection of H202 without closure in management of PNS. Injection of H202 into the pilonidal tracts can give a precise delineation of the affected tracts, which can be excised with minimal amount of surrounding normal tissues and hence lead to a quicker recovery and low recurrence rate. PMID- 24229014 TI - Prophylactic and informational abdominal drainage is not necessary after colectomy and suprapromontory anastomosis. AB - Several randomized prospective studies in western countries regarding the usefulness of prophylactic drainage have concluded that prophylactic abdominal drainage tubes are unnecessary. In Japan, however, longitudinal and vascular margins are rather different from in western countries. Furthermore, body mass index and volume of mesentery differed. Thus, although it is a retrospective study, it is worth investigating the usefulness of prophylactic drainage in the Japanese context. Two hundred sixty patients underwent colectomy and suprapromontory anastomosis. Prophylactic drainage tubes were inserted in 124 cases (47%) and not inserted in 136 cases (53%). In terms of postoperative complications, no statistically significant difference was found between the with drainage and the without-drainage groups. The incidence of the abscess formation was not statistically different in the with-drainage group (4.0%) or the without drainage group (0.7%). We concluded that the prophylactic and informational drainage tubes are not necessary even in Japanese cases of suprapromontory anastomosis, which typically have a wide resection and regional lymphadenectomy containing the roots of regional vessels. PMID- 24229015 TI - A long-term survival case of rectal cancer with multiple pulmonary metastases treated with multidisciplinary chemotherapy. PMID- 24229016 TI - A case of benign schwannoma of the ascending colon treated with laparoscopic assisted wedge resection. AB - Isolated colonic schwannomas are rare gastrointestinal mesenchymal tumors. Only a small number of cases have been reported. Occurrence of these tumors is more common in the stomach than in the large intestine. These spindle cell lesions are distinct from leiomyoma, leiomyosarcoma, and gastrointestinal stromal tumors because the tumor cells have a distinct immunophenotype, with strong diffuse positivity for S-100 and vimentin, as well as corroborative negative staining of CD117 and smooth muscle markers. We present a case of colonic schwannoma in a 70 year-old woman who had no specific symptoms. The patient was diagnosed with a submucosal tumor in the ascending colon on colonoscopy and abdominal computed tomography. Laparoscopic-assisted wedge resection of colon was performed. The very rare pathologic diagnosis of ascending schwannoma was made postoperatively. This case is interesting because schwannomas of the colon and rectum are extremely rare and are treated by laparoscopic-assisted wedge resection. PMID- 24229017 TI - Recurrent pilonidal sinus: lay open or flap closure, does it differ? AB - Treatment options of pilonidal sinus, which has high recurrence rates, is still controversial. In this study, we aimed to analyze for possible factors affecting recurrence. Forty-one patients with recurrent pilonidal sinus were included in this study. Of them, 33 were male and 9 were female (mean age, 24.9 years; age range, 16-42). Factors (i.e., risk factors) were detected in 32 patients. Excision-secondary healing and lay open was performed on 30 of the patients admitted with recurrence. Excision and flap closure was applied on 11 patients. Our recurrence rate was 9.7%. The recurrence rate of our study is compatible with the literature. Comparative studies are needed to determine the appropriate method to decrease recurrence rate. PMID- 24229018 TI - Hepatic inflammatory pseudotumor with elevated serum CA19-9 level mimicking liver metastasis from rectal cancer: report of a case. AB - Inflammatory pseudotumor (IPT) of the liver is rare, and differential diagnosis from malignant tumors is difficult. We herein report a case of IPT of the liver with marked elevation of carbohydrate antigen 19-9 (CA19-9). A 72-year-old woman, who underwent low anterior resection for rectal cancer, had low-grade fever and epigastric pain. The patient has well-controlled idiopathic thrombocytopenic purpura (ITP) with steroid maintenance treatment. Abnormal laboratory findings included serum carcinoembryonic antigen of 15.9 ng/mL and CA19-9 up to 14,632 U/mL. Computed tomography revealed a low-density lesion, and magnetic resonance imaging demonstrated a high intensity lesion on T1, T2-weighted, and diffusion weighted images (55 * 22 mm in the Couinaud's segment 4 of the liver). However, 1 month after the appearance of the symptom, serum level of CA19-9 suddenly decreased to 37 U/mL. The tumor decreased spontaneously to 20 * 10 mm. Seven months later, the tumor had reduced to 18 * 11 mm. With a diagnosis of IPT, the patient remains well without regrowth of the tumor at 1 year follow-up after CA19 9 decrease to normal limits. PMID- 24229019 TI - Laparoscopy-assisted resection of ileocecal intussusception caused by ileal pedunculated lipoma. AB - We report on a case of ileal lipoma that prolapsed into the ascending colon and was resected by laparoscopy-assisted surgery. A 31-year-old male Japanese patient was admitted to our hospital because of hematochezia and anemia. Colonoscopy revealed a pedunculated polyp arising from the ileum. The surface was covered with slightly edematous mucosa. Abdominal computed tomography showed a low density mass in the ascending colon. A diagnosis of pedunculated ileal lipoma with intussusception was made, and laparoscopy-assisted surgery was performed. The intussusception was reducted by resection of the lipoma. The surgical specimen was a 40 * 30 * 25 mm round tumor with a long stalk 11 cm in length. Microscopic examination of the specimen revealed ileal lipoma. Laparoscopic surgery is recommended for benign tumors of the small intestine because it is minimally invasive. PMID- 24229020 TI - Identification of preoperative risk factors associated with the conversion of laparoscopic to open appendectomies. AB - Our goals were to (1) identify risk factors associated with conversion from laparoscopic to open appendectomies and (2) establish criteria that predict the possibility of conversion to an open technique. We did a retrospective chart review of all patients who underwent laparoscopic appendectomies during a 5-year period (2004-2008). Preoperative risk factors, intraoperative findings, and postoperative complications were compared. We found that of 763 patients who had undergone laparoscopic appendectomy, 44 patients were converted to open technique (conversion rate of 5.8%). For these 44 patients, the male to female ratio was 2 to 1, and the men were older (45 versus 37 years of age, P < 0.001). Conversion rates decreased with time (8.7% in 2004 versus 3.5% in 2008). Past surgical history was insignificant. However, a duration of symptoms of >5 days as well as a white blood cell count >20,000 were found to have a direct correlation. Incidence of postoperative complications did not increase in converted patients. The conversion rate is highest in male patients above 45 years of age, with over 5 days' duration of symptoms, leukocytosis >20,000, and ruptured appendicitis on computed tomography scan. The presence of 3 to 4 of these risk factors should lower the threshold for consideration of conversion to open appendectomy. PMID- 24229021 TI - Favorable response after gemcitabine-radiotherapy for invasive pancreatic intraductal papillary mucinous neoplasm: a case report. AB - The efficacy of chemoradiotherapy for invasive pancreatic ductal carcinoma derived from an intraductal papillary mucinous neoplasm (IPMN) has not been established. The subject of the present report was a 53-year-old man admitted for the treatment of IPMN. The tumor, located in the pancreatic body, was of the mixed type of IPMN, and it involved the branch duct, where it was 38 mm in diameter, and the main duct, where it was 6 mm in diameter. Distal pancreatectomy was performed and the postoperative course was uneventful; however, histopathologic diagnosis revealed invasive ductal carcinoma with a positive surgical margin in the pancreatic duct. Although total pancreatectomy was recommended, chemoradiotherapy (50.4-Gy irradiation and gemcitabine) was preferred by the patient. At 9-month follow up, computed tomography and magnetic resonance imaging showed a cystic mass at the surgical margin of the pancreas. Endoscopic ultrasonography showed a 44-mm cystic lesion with nodules in the remnant pancreas, on the basis of which he underwent total pancreatectomy. Pathologic examination of the resected specimen revealed absence of the epithelium at the surgical margin of the main pancreatic duct, and malignant cells were not detected. PMID- 24229022 TI - Surgical approach to splenic hydatid cyst: single center experience. AB - The benefits and risks of surgery for splenic hydatid cyst (SHC) remain controversial. We aimed to share our experience about a surgical approach for SHC. Sixteen consecutive patients with SHC disease who underwent open splenectomy at our hospital between January 2006 and July 2012 were retrospectively evaluated. Data on the patients' demographic features, clinical findings, radiological and serological diagnostic methods, and surgical and medicinal treatment options were collected and used to generate descriptive profiles of diagnosis, treatment course, and outcome. The patient population was composed of 6 females and 10 males, with an age range of 18 to 79 years (mean age: 47.0 +/- 18.0). Radiological examinations detected hydatid cysts in spleen alone (n = 7) or both spleen and liver (n = 9). Preoperative serological testing identified 13 of the patients as IHA positive. All except 1 patient received a 10- to 21-day preoperative course of albendazole therapy and all patients received vaccination 1 week prior to surgery. Seven patients underwent splenectomy. The remaining patients underwent splenectomy with partial cystectomy and omentopexy (n = 6), partial cystectomy and unroofing (n = 1), pericystectomy (n = 1), or pericystectomy with partial nephrectomy (n = 1). All except one patient received a 10- to 45-day postoperative course of albendazole. No patients developed serious complications or signs of recurrence during the follow-up. The clinical profile of SHC disease at our hospital includes diagnosis by radiological methods, splenectomy treatment by simple or concomitant procedures according to the patient's symptoms, cyst size, number and localization, and compression of adjacent organs, and adjunct vaccination to decrease risk of postoperative septic complications. This profile is associated with low risk of complications and high therapeutic efficacy. PMID- 24229023 TI - Routine histopathologic examination of appendectomy specimens: retrospective analysis of 1255 patients. AB - The objective of this study was to analyze the clinical benefit of histopathologic analysis of appendectomy specimens from patients with an initial diagnosis of acute appendicitis. We retrospectively analyzed the demographic and histopathologic data of 1255 patients (712 males, 543 females; age range, 17-85 years) who underwent appendectomy to treat an initial diagnosis of acute appendicitis. Patients who underwent incidental appendectomy during other surgeries were excluded from the study. Histopathologic findings of the appendectomy specimens were used to confirm the initial diagnosis. Ninety-four percent of the appendectomy specimens were positive for appendicitis. Of those, 880 were phlegmonous appendicitis, 148 were gangrenous appendicitis with perforation, and the remaining 88 showed unusual histopathologic findings. In the 88 specimens with unusual pathology, fibrous obliteration was observed in 57 specimens, carcinoid tumor in 11, Encheliophis vermicularis parasite infection in 8, granulatomous inflammation in 6, appendiceal endometriosis in 2, and 1 specimen each showed mucocele, eosinophilic infiltration, Taenia saginata parasite infection, and appendicular diverticulitis. All carcinoid tumors were located in the distal appendix. Six of the 11 carcinoid tumors were defined by histopathology as involving tubular cells, and the other 5 as involving enterochromaffin cells. Six patients had muscularis propria invasion, 2 patients had submucosa invasion, 2 patients had mesoappendix invasion, and 1 patient had serosal invasion. All patients with tumors remained disease free during the follow-up (range, 1-27 months). We conclude that when the ratio of unusual pathologic findings for appendectomy specimens is considered, it is evident that all surgical specimens should be subjected to careful histologic examination. PMID- 24229024 TI - Port site metastasis after laparoscopic-assisted distal gastrectomy (LADG). AB - This report describes a case of port site metastasis after laparoscopic gastrectomy for gastric cancer. A 57-year-old man with clinical cTNM stage II (T2 N0 M0) gastric cancer was admitted to our hospital. After administration of an oral fluoropyrimidine drug (S-1) for 2 weeks, he underwent laparoscopy-assisted distal gastrectomy (LADG). On hematoxylin and eosin staining, the pTNM stage was IA (T1b N0 M0). Eighteen months later, the patient developed a subcutaneous metastasis at the trocar site. A second operation was performed, and the abdominal wall mass was resected. The histological finding confirmed a diagnosis of metastatic gastric carcinoma. Immunohistochemical analysis revealed micrometastasis in fat tissue adjacent to the lymph node near the left gastric artery. Surgeons should be aware that port site metastasis can occur in patients undergoing LADG for gastric cancer with lymphatic micrometastasis, which is undetectable on routine hematoxylin and eosin staining. PMID- 24229025 TI - Abdominal implantation of testicles in the management of intractable testicular pain in Fournier gangrene. AB - Fournier gangrene (FG) is a necrotizing soft tissue infection involving the superficial and fascial planes of the perineum. In many cases of FG, debridement of the scrotum is necessary, leaving definitive management of the exposed testicles a significant surgical challenge. Frequent incidental trauma to the testicles can cause severe pain, especially in laborers. Practical surgical solutions are few and not well detailed. Various options exist, including creating a neoscrotum with adjacent thigh tissue, split-thickness skin grafts (STSGs), or even creating a subcutaneous thigh pocket. We describe a case of abdominal implantation of bilateral testicles for persistent testicular pain in a case where STSGs did not provide adequate protection, adjacent thigh skin was not available for creation of a neoscrotum, and significant cord contracture occurred. We detail the advantages and disadvantages of the commonly described techniques, including this approach, and how in select individuals this may be a suitable alternative. PMID- 24229026 TI - Expression of GLUT-1 and GLUT-3 in xanthogranulomatous cholecystitis induced a positive result on 18F-FDG PET: report of a case. AB - Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET. PMID- 24229027 TI - Critical analysis of Strattice performance in complex abdominal wall reconstruction: intermediate-risk patients and early complications. AB - The purpose of this study was to analyze the performance of a porcine-derived acellular dermal matrix (Strattice Reconstructive Tissue Matrix) in patients at increased risk for perioperative complications. We reviewed medical records for patients with complex abdominal wall reconstruction (AWR) and Strattice underlay from 2007 to 2010. Intermediate-risk patients were defined as having multiple comorbidities without abdominal infection. Forty-one patients met the inclusion criteria (mean age, 60 years; mean body mass index, 35.5 kg/m(2)). Comorbidities included coronary artery disease (63.4%), diabetes mellitus (36.6%), and chronic obstructive pulmonary disease (17.1%). Fascial closure was achieved in 40 patients (97.6%). Average hospitalization was 6.4 days (range, 1-24 days). Complications included seroma (7.3%), wound dehiscence with Strattice exposure (4.9%), cellulitis (2.4%), and hematoma (2.4%). All patients achieved abdominal wall closure with no recurrent hernias or need for Strattice removal. Patients with multiple comorbidities at intermediate risk of postoperative complications can achieve successful, safe AWR with Strattice. PMID- 24229028 TI - Stapleless laparoscopic splenectomy using harmonic scalpel by 2-step sealing. AB - Laparoscopic splenectomy (LS) has been accepted as a safe and effective procedure as compared with open splenectomy. Recently, there have been a few reports on the LigaSure vessel sealing system as an alternative hemostasis to clip ligation. Here we report the experience of LS using an alternative energy device, Harmonic Scalpel laparoscopic coagulating shears (LCS). Preliminary experience of LS with LCS for a patient with idiopathic thrombocytopenic purpura (ITP) is reported. Generally, two-step sealing with LCS was used for vessels of the splenic pedicle approximately 5 mm in diameter without using the Endo-GIA stapler. Operative time was 93 minutes, and blood loss was 40 mL. The patient was discharged on the third postoperative day with no intraoperative or postoperative complications. The LS with LCS was performed safely using two-step sealing. Further experience is necessary to verify the safety of this procedure. PMID- 24229029 TI - Tumor compression-induced portal obstruction and selective transarterial chemoembolization increase functional liver volume in the unobstructed area, facilitating successful resection of a large HCC. AB - A 62-year-old man with hepatitis B was admitted for treatment of a large hepatocellular carcinoma. The right portal vein was completely obstructed by tumor compression. Although we initially planned a right trisectionectomy as curative hepatectomy, the percentage of future remnant liver volume (%RLV) and the percentage of functional liver volume (%RFLV) were 31.2% and 41.3%, respectively. Because %RFLV showed marginal tolerability for curative hepatectomy and %RLV was very low, we opted for transarterial chemoembolization of segment IV and the right lobe containing the tumor as an approach to selectively reduce liver volume and abolish liver function. One month later, %RLV and %RFLV had dramatically increased to 46.6% and 67.2%, resulting in curative hepatectomy. Our results suggest that tumor compression-induced portal obstruction and selective transarterial chemoembolization increase %RFLV much more than %RLV. This may represent a useful approach in preoperative management in patients with large hepatocellular carcinomas to improve %RFLV for hepatic resection. PMID- 24229030 TI - Adult intussusception of appendicular mucinous cystoadenoma. AB - Intussusception is a rare cause of adult intestinal obstruction. Clinical manifestations are not specific, which makes a preoperative diagnosis difficult to establish and often causes delay. We report a case of acute intestinal obstruction due to ileocolic intussusception. An emergency laparoscopy was performed revealing an obstructive mass at the ileocecal region resulting from an appendicular tumor. A right hemicolectomy was conducted. The pathologic examination of the resected sample concluded the mass comprised an appendicular mucinous cystoadenoma. We discuss the clinical features, preoperative diagnosis, and surgical strategies of adult intussusception, as well as the uncommon finding of an appendicular mucinous tumor as its causative lesion, with a review of the available literature. PMID- 24229031 TI - A systematic review of outcomes following repair of complex ventral incisional hernias with biologic mesh. AB - Repair of contaminated/infected ventral incisional hernias is marked by high rates of recurrence, complications, and/or explantation of synthetic mesh. Biologic mesh products are recommended for repair to permit reconstruction and reduce complications. A systematic review of PubMed, EMBASE, and Cochrane databases identified English-language articles reporting postoperative outcomes (e.g., hernia recurrence, infection, mesh explantation) in patients undergoing contaminated/infected ventral incisional herniorrhaphy. Eleven studies met inclusion criteria and contained quantitative outcome data. All were retrospective chart reviews of biologic mesh use (mostly human acellular dermal matrix). Hernia recurrence and wound infection rates were highly variable and inconsistently reported across studies. Mesh explantation was rarely reported. Outcome variability is likely owing to heterogenous patient populations, surgical technique variations, and follow-up duration. Biologic mesh use in contaminated/infected herniorrhaphy was marked by low reported rates of secondary surgeries for infected mesh removal. Data from large, well-controlled, prospective trials with biologic mesh products are needed. PMID- 24229032 TI - Small intestinal strangulation due to a rare type of primary internal hernia. AB - Internal hernias in which the gate is located in the paracolic gutter are rare. A 75-year-old man was admitted to our hospital with severe epigastric pain without past history of laparotomy and/or trauma. He was diagnosed with strangulation of the ileum by the findings of computed tomography, and the operation was performed. During laparotomy, the small intestine was found to be strangulated and to enter the retroperitoneum from the right paracolic gutter near the hepatic flexure. The patient was diagnosed with an internal hernia, which differed from a pericecal hernia in that the hernia gate was located along the paracolic gutter near the hepatic flexure far from the cecum. Hence, it was considered to be a rare type of internal hernia. We report the clinical presentation and imaging findings of this rare internal hernia. PMID- 24229033 TI - Incisional intercostal hernia with prolapse of the colon after right partial nephrectomy. AB - A 75-year-old woman with a history of myocardial infarction, gallstones, and right renal cancer was referred to our department because of right flank pain. She had a surgical scar on the right abdomen between the 10th and 11th ribs; computed tomography demonstrated intercostal herniation of the colon. Recognizing the possibility of adhesions of the hernia and colon, we used a median skin incision and patched a polyester mesh coated with absorbent collagen. The patient had an uneventful postoperative course, with no pain for 6 months postoperatively. Transdiaphragmatic intercostal hernias with abdominal contents commonly develop after trauma or thoracic surgery. Incisional intercostal hernias seldom develop after nephrectomy; the present case is only the fourth report. We conjecture that a costochondral incision can induce subluxation of the costotransverse joint, intercostal nerve injury, and atrophy of the intercostal and abdominal oblique muscles. Surgeons must therefore recognize the potential, albeit rare, for intercostal hernia after nephrectomy. PMID- 24229034 TI - Assessment of the effectiveness of silver-coated dressing, chlorhexidine acetate (0.5%), citric acid (3%), and silver sulfadiazine (1%) for topical antibacterial effects against the multi-drug resistant Pseudomonas aeruginosa infecting full skin thickness burn wounds on rats. AB - The aim of this study was to compare the effects of four different topical antimicrobial dressings on a multi-drug resistant Pseudomonas aeruginosa contaminated full-thickness burn wound rat model. A total of 40 adult male Wistar albino rats were used. The control group (group 1), silver sulfadiazine (1%) group 2, chlorhexidine acetate (0.5%) group 3, citric acid (3%) group 4, and silver-coated dressing group 5 were compared to assess the antibacterial effects of a daily application to a 30% full-skin thickness burn wound seeded 10 minutes earlier with 10(8) CFU (colony forming unit)/0.5 mL of a multi-drug resistant Pseudomonas aeruginosa strain. Five groups (1 control group and 4 treatment groups) were compared. The administration of third-degree burns to all rats was confirmed based on histopathologic data. The tissue cultures from groups 2 and 5 exhibited significant differences compared to those of the other 3 groups, whereas no significant differences were observed between groups 1, 3, and 4. The effectiveness of the treatments was as follows: 1% silver sulfadiazine > silver coated dressing > 3% citric acid > 0.5% chlorhexidine acetate > control group. Our results supported the efficacy of topical therapy by silver sulfadiazine and silver-coated dressing on infections caused by multi-drug resistant Pseudomonas spp. PMID- 24229035 TI - Repeat liver resection for hepatocellular carcinoma complicating primary biliary cirrhosis. AB - The incidence of hepatocellular carcinoma (HCC) complicating primary biliary cirrhosis (PBC) is between 0.7% and 16%. Repeat liver resection for recurrent HCC complicating PBC is not usually performed and not published because this approach is not generally applicable due to liver dysfunction. We applied repeat liver resection for these diseases. Three patients were diagnosed with PBC. The first HCC was noted at a mean of 6 years (4-17 years) after diagnosis of PBC. The second HCC occurred at a mean of 2.5 years (0.4-3 years) after the first surgery. All patients were treated with curative resection on first and second surgery. The mean overall survival time after the first liver resection was 46 months. Repeat liver resection for recurrent HCC complicating PBC is an option and may improve the outcome. PMID- 24229036 TI - A case of living donor liver transplant recipient treated with novel blood purification "plasma diafiltration". AB - Blood purification therapy is indispensable for liver transplant recipients. The case of a living donor liver transplant recipient who represented graft insufficiency and was supported by novel blood purification "plasma diafiltration" immediately after operation is presented. A 60-year-old woman was referred for living donor liver transplant because of liver cirrhosis due to hepatitis C. Elective living donor liver transplant was performed, but the graft was small for size. Thus, the signs of graft insufficiency appeared immediately after the operation, and plasma diafiltration was used as a bridge to graft regeneration. After plasma diafiltration was started, the recipient recovered promptly, and withdrawal was performed 35 hours after induction without any complications. Plasma diafiltration is a useful and safe liver support for liver transplant recipients, including immediately after liver transplantation. PMID- 24229037 TI - Two rare metachronous metastases of hepatocellular carcinoma after liver transplantation. AB - A 59-year-old male with hepatocellular carcinoma (HCC) due to liver cirrhosis caused by the hepatitis C virus underwent cadaveric whole liver transplantation. Two years later, he had a metastatic HCC in the superior mediastinum. Over the following postoperative year, he underwent transcatheter arterial chemoembolization (TACE) for 4 tumors in the implanted liver. In the third post TACE month, he was emergently hospitalized due to intracerebral hematoma with a tumor invading the bone in the medial frontal segment. He underwent emergency intracranial tumorectomy and hemorrhage removal. The histopathologic diagnosis was metastatic HCC. He regained consciousness as well as the ability to speak and to feed himself, resulting in an improved quality of life. The incidence of HCC recurrence after liver transplantation is observed in approximately 8% to 11% of selected cases, with frequent relapses observed in the implanted liver, bones, adrenal glands, and lungs. Mediastinal and intracranial metastases from HCC post liver transplantation are very rare. PMID- 24229038 TI - Trigger finger release with stepwise preservation of the A1 pulley: a functional pulley-preserving technique. AB - The first annular (A1) pulley is an important structure of the hand, providing a biomechanical support to the metacarpophalangeal joint and maintaining joint stability and flexor tendon alignment. Albeit uncommon, disruption of this pulley can result in dislocation or ulnar drift of the digit, particularly pronounced in patients with rheumatoid arthritis. Despite this, the A1 pulley is commonly divided without reconstruction in trigger finger. Several annular pulley reconstructive techniques have been developed to preserve its function. However, development of recurrent triggering has been observed due to fibrosis, largely due to inadequate release of the pulley. We have developed a technique to increase the volume within the flexor sheath while preserving the A1 pulley by way of stepwise lengthening. This has enabled an increase in the diameter of the pulley to 4 times its original size. A prospective study was performed comprising 10 trigger finger releases with stepwise lengthening of the A1 pulley. In all patients, there were no complications, and good hand function was achieved with no recurrence of triggering at 6 weeks of follow-up. This technique can thus safely achieve trigger release without sacrifice of the function of the A1 pulley. PMID- 24229039 TI - Hemoptysis and acute respiratory syndrome (ARDS) as delayed-type hypersensitivity after FOLFOX4 plus bevacizumab treatment. AB - As there have been many multidrug regimens introduced in colorectal cancer treatment, hypersensitivity is more often encountered than in the past. Though most allergic adverse events of oxaliplatin are mainly classified as type I reaction, a limited number of case reports of type IV reaction (delayed-type hypersensitivity) have been reported. A 73-year-old man was hospitalized for receiving the third cycle of FOLFOX4 plus bevacizumab. Forty-two hours after administration, he had dyspnea and hemoptysis. Acute respiratory distress syndrome was suspected, and the patient underwent mechanical ventilation and steroid pulse therapy. Delayed-type hypersensitivity is induced by induction of inflammation via IL-1, TNF-alpha and IL-6. The serum level of IL-6 in patients with advanced colorectal cancers is usually greater than the normal range. Therefore, delayed-type hypersensitivity may be easily induced in those patients. We should pay special attention to delayed-type hypersensitivity in advanced colorectal cancer patients undergoing FOLFOX treatment. PMID- 24229040 TI - Clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma: experience at a single institution. AB - This retrospective study investigated the clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma (BSC). Among 190 patients with esophageal carcinoma treated surgically between 1998 and 2011, we identified 9 (4.7%) with BSC. All of the patients were male, with a median age of 65 years. The frequencies of venous invasion, lymphatic invasion, and lymph node metastasis were 56%, 89%, and 67%, respectively. A total of 2 patients were pathologic stage 1, 5 were stage 2, and 2 were stage 3. Tumor recurrence was observed in 56% of the patients. The 5-year survival rate for patients with esophageal BSC was 40%, which was compatible with the figure of 53.8% for control patients (n = 18) with typical squamous cell carcinoma matched for sex, age, tumor location, and pathologic stage (P = 0.45). Although esophageal BSC shows aggressive lymph-vascular invasion and has a high likelihood of recurrence, its prognosis seems identical to that of typical squamous cell carcinoma. PMID- 24229041 TI - Gastric bronchogenic cyst histologically diagnosed after laparoscopic excision: report of a case. AB - Abdominal computed tomography of a 71-year-old man revealed a 3-cm mass in gastric cardia. Although the mass was widely attached to the gastric wall, no clear contrast enhancement was observed. Abdominal magnetic resonance imaging revealed the mass to have homogenous high intensity on T2W1 images and isointensity on T1W1 images. On diffusion-weighted imaging, no high intensity was observed. However, the mass had a smooth surface and was widely attached to the gastric wall, consistent with computed tomography findings. A gastric submucosal tumor was suspected. Laparoscopic tumor resection was performed. Histopathologic diagnosis of the mass was a bronchogenic cyst derived from the respiratory primordium originating in the foregut of the primitive intestine. Such cysts are mostly found in the mediastinum or thoracic cavity; their occurrence on the gastric wall is extremely rare. Despite this, we think that bronchogenic cysts should be considered in the differential diagnosis of abdominal unilocular cystic diseases. PMID- 24229042 TI - Video-assisted thoracoscopic surgery for localized neurofibroma of the esophagus: case report and review of the literature. AB - Esophageal submucosal tumors are less common than other gastrointestinal tract tumors. Leiomyoma is the most common benign esophageal SMT, accounting for more than 70% of these tumors. We report on a case of a 56-year-old woman with a 3-cm diameter midthoracic esophageal submucosal tumor. Magnetic resonance imaging suggested leiomyoma or neurofibroma. Video-assisted thoracoscopic surgery was performed to enucleate the tumor from the esophageal wall by splitting the muscle layers. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. Immunohistochemical staining confirmed the diagnosis of esophageal neurofibroma. Gastrointestinal tract involvement of neurofibromatous lesions is rare and occurs most frequently as a systemic manifestation of von Recklinghausen disease. Cases of localized esophageal neurofibroma with prior or subsequent evidence of generalized neurofibromatosis have rarely been documented. This is a rare case of isolated esophageal neurofibroma without classic systemic manifestations of generalized neurofibromatosis, and it is the first reported case treated by video-assisted thoracoscopic surgery. PMID- 24229043 TI - Successful treatment by balloon angioplasty under portography for late-onset stenosis of portal vein after cadaveric liver transplantation. AB - A 69-year-old woman, who underwent cadaveric liver transplantation for non-B, non C liver cirrhosis with hepatocellular carcinoma in April 2009, was admitted to our hospital because of graft dysfunction. Enhanced computed tomography revealed stenosis of the left branch of the portal vein, obstruction of the right branch of the portal vein at porta hepatis, and esophagogastric varices. Balloon angioplasty of the left branch of the portal vein under transsuperior mesenteric venous portography was performed by minilaparotomy. After dilatation of the left branch of the portal vein, the narrow segment of the portal vein was dilated, which resulted in reduction of collateral circulation. At 7 days after balloon angioplasty, esophageal varices were improved. The patient made a satisfactory recovery, was discharged 8 days after balloon angioplasty, and remains well. PMID- 24229044 TI - The contemporary status of Czech surgery, its successes, and its directions for further development. PMID- 24229046 TI - No nitrification in lakes below pH 3. AB - Lakes affected by acid mine drainage (AMD) or acid rain often contain elevated concentrations of ammonium, which threatens water quality. It is commonly assumed that this is due to the inhibition of microbial nitrification in acidic water, but nitrification was never directly measured in mine pit lakes. For the first time, we measured nitrification by (15)NH4Cl isotope tracer addition in acidic as well as neutral mine pit lakes in Spain and Germany. Nitrification activity was only detected in neutral lakes. In acidic lakes no conversion of (15)NH4(+) to (15)NO3(-) was observed. This was true both for the water column as well as for biofilms on the surface of macrophytes or dead wood and the oxic surface layer of the sediment. Stable isotope analysis of nitrate showed (18)O values typical for nitrification only in neutral lakes. In a comparison of NH4(+) concentrations in 297 surface waters with different pH, ammonium concentrations higher 10 mg NH4-N L(-1) were only observed in lakes below pH 3. On the basis of the results from stable isotope investigations and the examination of a metadata set we conclude that the lower limit for nitrification in lakes is around pH 3. PMID- 24229047 TI - Dynamic Stokes shift of the time-resolved phosphorescence spectrum of Zn(II) substituted cytochrome c. AB - The dynamic phosphorescence Stokes shift (PSS) response of Zn(II)-substituted cytochrome c (ZnCytc) was detected using the time-resolved phosphorescence spectrum of the intrinsic Zn(II)-porphyrin chromophore, which senses the motions of the surrounding protein and hydration shell. The phosphorescence spectrum of ZnCytc exhibits resolved vibronic structure arising from in-plane deformations of the porphyrin macrocycle, as is also observed in the absorption and fluorescence spectra. As the emission time increases, the phosphorescence spectrum shifts to the red without incurring a significant change in vibronic structure or line shape, so the shift arises from dynamic solvation, the reorganizational motions of the protein and solvent that occur in response to formation of the first excited triplet state. A correlation time of 294 +/- 14 MUs was obtained from a single-exponential fit to the time dependence of the mean emission frequency of the T(0,0) peak in the phosphorescence spectrum. This time scale is consistent with a diffusive sampling of the native structure's minimum due to global or collective conformational fluctuations. We suggest that studies of the PSS response sensed in proteins by an intrinsic probe will be informative of protein and hydration-shell dynamics over the microsecond-millisecond time regimes associated with biological function. PMID- 24229048 TI - (Co)polymers of chlorotrifluoroethylene: synthesis, properties, and applications. PMID- 24229049 TI - Risk of subarachnoid haemorrhage in people admitted to hospital with selected immune-mediated diseases: record-linkage studies. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating cause of stroke, occurring in relatively young people. It has been suggested that some immune mediated diseases may be associated with an increased risk of SAH. METHODS: We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999-2011). Rate ratios for SAH were determined, comparing immune-mediated disease cohorts with comparison cohorts. RESULTS: There were significantly elevated risks of SAH after hospital admission for the following individual immune-mediated diseases: Addison's disease, ankylosing spondylitis, autoimmune haemolytic anaemia, Crohn's disease, diabetes mellitus, idiopathic thrombocytopenia purpura, myxoedema, pernicious anaemia, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, SLE and thyrotoxicosis. Elevated risks that were greater than 2-fold were found for Addison's disease (rate ratio (RR) = 2.01, 95% confidence interval 1.3-2.97), idiopathic thrombocytopenia purpura (RR = 2.42, 1.86-3.11), primary biliary cirrhosis (RR = 2.21, 1.43-3.16) and SLE (RR = 3.76, 3.08-4.55). CONCLUSIONS: Our findings strongly support the suggestion that patients with some immune-mediated diseases have an increased risk of SAH. Further studies of the mechanisms behind this association are warranted. PMID- 24229050 TI - Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance. AB - To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-alpha-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross linking to form a uniform particle size of 140-180 nm with ~40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5-199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin. PMID- 24229051 TI - The aniline-to-azobenzene oxidation reaction on monolayer graphene or graphene oxide surfaces fabricated by benzoic acid. AB - The oxidation of aniline to azobenzene was conducted in the presence of either monolayer graphene (EG) or graphene-oxide-like surface, such as GOx, under ultra high vacuum conditions maintaining a 365-nm UV light exposure to enhance the oxidation reaction. The surface-bound products were investigated using micro Raman spectroscopy, high-resolution photoemission spectroscopy, and work function measurements. The oxygen carriers present on the GOx surfaces, but not on the EG surfaces, acted as reaction reagents to facilitate the oxidation reaction from aniline to azobenzene. Increasing the aniline concentration at 300 K confirmed that the exchange ratio from the aniline to the azobenzene was enhanced, as determined by the intensity ratio between the aniline- and azobenzene-induced N 1 s core-level spectra. The work function changed dramatically as the aniline concentration increased, indicating that the aniline on the GOx surface conveyed n-type doping characteristics at a low coverage level. A higher aniline concentration increased the p-type doping character by increasing the azobenzene concentration on the GOx surface. A comparison of the oxidation reactivity of aniline molecules on the EG or GOx surfaces revealed the role of the oxygen carriers on the GOx surfaces in the context of catalytic oxidation. PMID- 24229052 TI - Analyzing protein micro-heterogeneity in chicken ovalbumin by high-resolution native mass spectrometry exposes qualitatively and semi-quantitatively 59 proteoforms. AB - Taking chicken Ovalbumin as a prototypical example of a eukaryotic protein we use high-resolution native electrospray ionization mass spectrometry on a modified Exactive Orbitrap mass analyzer to qualitatively and semiquantitatively dissect 59 proteoforms in the natural protein. This variety is largely induced by the presence of multiple phosphorylation sites and a glycosylation site that we find to be occupied by at least 45 different glycan structures. Mass analysis of the intact protein in its native state is straightforward and fast, requires very little sample preparation, and provides a direct view on the stoichiometry of all different coappearing modifications that are distinguishable in mass. As such, this proof-of-principal analysis shows that native electrospray ionization mass spectrometry in combination with an Orbitrap mass analyzer offers a means to characterize proteins in a manner highly complementary to standard bottom-up shot gun proteome analysis. PMID- 24229054 TI - Summary and recommendations: highlights of the asthma summit 2009: beyond the guidelines. PMID- 24229053 TI - Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series. AB - CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: 'breast cancer' and 'lymph node' and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types. PMID- 24229056 TI - Free standing reduced graphene oxide film cathodes for lithium ion batteries. AB - We report the fabrication and electrochemical activity of free-standing reduced graphene oxide (RGO) films as cathode materials for lithium ion batteries. The conducting additive and binder-free RGO electrodes with different oxygen contents were assembled by a simple vacuum filtration process from aqueous RGO colloids prepared with the aid of cationic surfactants. The gravimetric capacity of RGO film cathodes showed clear dependence on the oxygen contents controlled by the thermal reduction process. The capacity increased with the increase of the amount of oxygen functional groups, indicating that the main lithium capturing mechanism of RGO cathodes is Li(+) ion interaction with the surface oxygen functionalities. The hydroxyl groups (C-OH) as well as carbon-oxygen double bonds have been identified as the lithiation-active species. The RGO cathodes achieved excellent rate capability due to the fast surface Faradaic reaction, suggesting that self supported RGO films are promising cathodes for high power application. The graphene oxide (GO)/RGO composite films showed inferior performance to those of RGO only. The poor electronic conductivity of GO might result in inefficient utilization of redox active oxygen functional groups despite the higher oxygen content and higher theoretical capacity of GO/RGO composite films. Further optimization on the amount of oxygen functional groups for higher capacity and better electronic conductivity would lead to the development of RGO based high energy-high power cathodes. PMID- 24229055 TI - Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review. AB - BACKGROUND: Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome. METHODS: We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05. RESULTS: A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02). CONCLUSIONS: Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined. PMID- 24229057 TI - Pathogenic mechanisms of idiopathic nonallergic rhinitis. AB - : Idiopathic nonallergic rhinitis (iNAR) has been difficult to define because of the long differential diagnosis of rhinopathy in the absence of allergic rhinitis. iNAR has traditionally been a diagnosis of exclusion with no clear unifying pathophysiology. Increased sensitivity to triggers such has climate changes, cold air, tobacco smoke, strong odors, and perfumes have been thought to be characteristic, but recent studies do not support this hypersensitivity hypothesis. New investigations of the local nasal environment and systemic "functional" syndromes have offered new insights into this condition. iNAR may be a heterogenous disorder that includes (1) anatomic abnormalities requiring nasal endoscopy for diagnosis, (2) incipient, local atopy (entopy), (3) dysfunction of nociceptive nerve sensor and ion channel proteins, and (4) autonomic dysfunction as found in chronic fatigue syndrome and other functional disorders. PMID- 24229058 TI - Decreasing aromaticity in pi-conjugated materials: efficient synthesis and electronic structure identification of cyclopentadiene-containing systems. AB - An efficient route to cyclopentadiene-containing pi-conjugated molecules is reported. A comparative analysis between the aryl/dienyl hybrids and their aromatic congeners shows a propensity of the diene moiety to reduce the optical band gap of a pi-conjugated system without compromising a planar structural topology. Moreover, a novel poly(fluorene) derivative bearing alternating cyclopentadiene repeat units was synthesized to demonstrate the applicability of this method in polymer synthesis. PMID- 24229059 TI - Tumefactive fibroinflammatory lesion presenting with head and neck fibrosclerosing lesions and orbital pseudotumors: a case report. AB - INTRODUCTION: Tumefactive fibroinflammatory lesion is an idiopathic fibrosclerosing disorder occurring in the head and neck region. It is one of a broad spectrum of entities named inflammatory pseudotumors and, as the name suggests, it mimics a lot of diseases such as malignancies or infections. Combined with its rarity, tumefactive fibroinflammatory lesion can be a tremendous diagnostic challenge. This case report describes a case of tumefactive fibroinflammatory lesion, which was initially thought to be peri-orbital and mandibular osteomyelitis caused by Aspergillus. A lengthy work up ensued and was required to reach the final diagnosis. CASE PRESENTATION: A 64-year-old Asian man with a history of diabetes mellitus and chronic kidney disease who was on hemodialysis presented with worsening exophthalmos and relapsing trismus. He was diagnosed as "mandibular osteomyelitis" about 20 years ago. Since then he had suffered chronic relapsing exophthalmos and jaw pain with numerous medical treatments. In 2011 he was diagnosed as peri-orbital and intramandibular aspergillosis because a serum Aspergillus galactomannan assay was positive. He was treated with multiple antifungal medications to no avail. A biopsy of his orbital lesions was not revealing. After repeated biopsies, we finally concluded that the patient was suffering from tumefactive fibroinflammatory lesion. Corticosteroid therapy was initiated with prompt response. CONCLUSIONS: Tumefactive fibroinflammatory lesion is a rare inflammatory benign tumor, which mimics many inflammatory and neoplastic disorders. Conventional work up including biopsy may not lead to the diagnosis without understanding this entity. Awareness of this disorder will aid early diagnosis and treatment. PMID- 24229060 TI - Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital. AB - BACKGROUND: Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs. METHODS: A nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring. RESULTS: A total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001). CONCLUSIONS: OLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs. PMID- 24229061 TI - Type D personality, quality of life and physical symptoms in the general population: a dimensional analysis. AB - OBJECTIVE: Type D personality, the interaction of negative affectivity (NA) and social inhibition (SI), has been associated with a range of adverse health related outcomes in cardiac patients and healthy participants. However, recent studies which have adopted a dimensional approach to Type D found no effect of Type D (NA * SI) on mortality or quality of life, after controlling for its constituent elements. To date, no study has determined if Type D is associated with negative health outcomes in healthy individuals when conceptualised as a dimensional variable. DESIGN: A cross-sectional self-report study with 177 healthy participants. MAIN OUTCOME MEASURES: Physical symptoms and quality of life. RESULTS: Using the traditional categorical analysis for Type D, it was found that Type D's report significantly more symptoms and significantly lower quality of life than non-Type D's report. However, when analysed as a dimensional construct (NA * SI), using multiple regression analysis, Type D (NA * SI) was not a significant predictor of physical symptoms or quality of life, after controlling for the main effects of NA and SI separately. CONCLUSION: These findings support those of recent studies that have identified null effects of Type D on outcome when analysed as a dimensional construct. PMID- 24229062 TI - Diagnosis and treatment of resistant hypertension. AB - Hypertension resistant to lifestyle interventions and antihypertensive medications is a common problem encountered by physicians in everyday practice. It is most often defined as a blood pressure remaining >= 140/90 mmHg despite the regular intake of at least three drugs lowering blood pressure by different mechanisms, one of them being a diuretic. It now appears justified to include, unless contraindicated or not tolerated, a blocker of the renin-angiotensin system and a calcium channel blocker in this drug regimen, not only to gain antihypertensive efficacy, but also to prevent or regress target organ damage and delay the development of cardiorenal complications. A non-negligible fraction of treatment-resistant hypertension have normal "out of office" blood pressures. Ambulatory blood pressure monitoring and/or home blood pressure recording should therefore be routinely performed to identify patients with true resistant hypertension, i.e. patients who are more likely to benefit from treatment intensification. PMID- 24229064 TI - Nanostructured macroporous bioanode based on polyaniline-modified natural loofah sponge for high-performance microbial fuel cells. AB - Microbial fuel cells (MFCs) are a promising technology to recover electrical energy from different types of waste. However, the power density of MFCs for practical applications is limited by the anode performance, mainly resulting from low bacterial loading capacity and low extracellular electron transfer (EET) efficiency. In this study, an open three-dimensional (3D) structured electrode was fabricated using a natural loofah sponge as the precursor material. The loofah sponge was directly converted into a continuous 3D macroporous carbon material via a simple carbonization procedure. The loofah sponge carbon (LSC) was decorated with nitrogen-enriched carbon nanoparticles by cocarbonizing polyaniline-hybridized loofah sponges to improve their microscopic structures. The macroscale porous structure of the LSCs greatly increased the bacterial loading capacity. The microscale coating of carbon nanoparticles favored EET due to the enhanced interaction between the bacteria and the anode. By using a single chamber MFC equipped with the fabricated anode, a power density of 1090 +/- 72 mW m(-2) was achieved, which is much greater than that obtained by similarly sized traditional 3D anodes. This study introduces a promising method for the fabrication of high-performance anodes from low-cost, sustainable natural materials. PMID- 24229063 TI - Evidence of the shifting baseline syndrome in ethnobotanical research. AB - BACKGROUND: The shifting baseline syndrome is a concept from ecology that can be analyzed in the context of ethnobotanical research. Evidence of shifting baseline syndrome can be found in studies dealing with intracultural variation of knowledge, when knowledge from different generations is compared and combined with information about changes in the environment and/or natural resources. METHODS: We reviewed 84 studies published between 1993 and 2012 that made comparisons of ethnobotanical knowledge according to different age classes. After analyzing these studies for evidence of the shifting baseline syndrome (lower knowledge levels in younger generations and mention of declining abundance of local natural resources), we searched within these studies for the use of the expressions "cultural erosion", "loss of knowledge", or "acculturation". RESULTS: The studies focused on different groups of plants (e.g. medicinal plants, foods, plants used for general purposes, or the uses of specific important species). More than half of all 84 studies (57%) mentioned a concern towards cultural erosion or knowledge loss; 54% of the studies showed evidence of the shifting baseline syndrome; and 37% of the studies did not provide any evidence of shifting baselines (intergenerational knowledge differences but no information available about the abundance of natural resources). DISCUSSION AND CONCLUSIONS: The general perception of knowledge loss among young people when comparing ethnobotanical repertoires among different age groups should be analyzed with caution. Changes in the landscape or in the abundance of plant resources may be associated with changes in ethnobotanical repertoires held by people of different age groups. Also, the relationship between the availability of resources and current plant use practices rely on a complexity of factors. Fluctuations in these variables can cause changes in the reference (baseline) of different generations and consequently be responsible for differences in intergenerational knowledge. Unraveling the complexity of changes in local knowledge systems in relation to environmental changes will allow the identification of more meaningful information for resource conservation. PMID- 24229065 TI - Characterization of freeze-dried gallic acid/xyloglucan. AB - BACKGROUND: Tamarind seed xyloglucan (TSX) is generally used for drug delivery systems. Gallic acid (GA) possesses various pharmacological activities. It has a good solubility and bioavailability but short half-life. PURPOSE: To prepare a sustained-release of GA to overcome its relatively short half-life. GA was blended with TSX and freeze-dried. The physicochemical properties of freeze-dried GA and freeze-dried GA/TSX were characterized, and the release profiles of GA from these freeze-dried samples were investigated. METHOD: All freeze-dried samples were characterized by PXRD, spectroscopic and thermal analyses. The dissolution studies were performed according to the United States Pharmacopeia (USP) XXX. RESULTS: According to FTIR, FT-Raman and (13)C CP/MAS NMR, the spectra of freeze-dried GA were similar to that of the anhydrous form. Nevertheless, DRIFTS and DSC were able to differentiate these two forms. The crystallinity of GA in the freeze-dried GA/TSX was the same as that of the freeze-dried GA. DSC indicates that there were interactions between GA and TSX. It was of interest that a freeze-dried sample with low amount of GA, 0.2% GA/1% TSX was mostly in an amorphous form. Moreover, all freeze-dried GA/TSX preparations demonstrated a sustained-release of GA compared to GA alone. The freeze-dried 1% GA/1% TSX provided the best sustained-release of GA of up to 240 min. CONCLUSIONS: TSX could change a crystal form of a small molecule to a mostly amorphous form. It was of importance that the freeze-dried GA/TSX could effectively retard the release of GA. These samples may be able to overcome the limitation for the therapeutic use of GA due to its short biological half-life. PMID- 24229066 TI - The DSM-5 - an interview with David Kupfer. AB - In this podcast we talk to Prof David Kupfer about the challenges, controversies and future directions of DSM-5 by considering other research frameworks and classification systems of disease, and how this revised psychiatric diagnostic manual will impact global mental health classification and the field of medicine. The podcast for this interview is available at: http://www.biomedcentral.com/sites/2999/download/Kupfer.mp3. PMID- 24229067 TI - Thermodynamics of block copolymers with and without salt. AB - Ion-containing block copolymers are of interest for applications such as electrolytes in rechargeable lithium batteries. The addition of salt to these materials is necessary to make them conductive; however, even small amounts of salt can have significant effects on the phase behavior of these materials and consequently on their ion-transport and mechanical properties. As a result, the effect of salt addition on block copolymer thermodynamics has been the subject of significant interest over the past decade. This feature article describes a comprehensive study of the thermodynamics of block copolymer/salt mixtures over a wide range of molecular weights, compositions, salt concentrations, and temperatures. The Flory-Huggins interaction parameter was determined by fitting small-angle X-ray scattering data of disordered systems to predictions based on the random phase approximation. Experiments on neat block copolymers revealed that the Flory-Huggins parameter is a strong function of chain length. Experiments on block copolymer/salt mixtures revealed a highly nonlinear dependence of the Flory-Huggins parameter on salt concentration. These findings are a significant departure from previous results and indicate the need for improved theories for describing thermodynamic interactions in neat and salt containing block copolymers. PMID- 24229068 TI - Birth order and myopia: what are the messages to readers? PMID- 24229069 TI - Having children, social characteristics, smoking and the risk of uveal melanoma: a case-control study. AB - PURPOSE: We analyzed data from the Risk Factors for Uveal Melanoma (RIFA) study to evaluate possible associations between uveal melanoma risk and having children, socioeconomic level and smoking. METHODS: The RIFA study was a German case-control study conducted from September 2002 to March 2005. The study population consisted of 455 incident uveal melanoma patients (20-74 years of age) and 827 matched (age, sex, region of residence) population controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Women with children showed an increased OR (1.59, 95% CI 0.95-2.66) for uveal melanoma development compared to women without children. We estimated decreased ORs for subjects with higher socioeconomic level compared to the lowest status (upper secondary school leaving certificate: OR 0.68, 95% CI 0.49-0.94; higher education: OR 0.60, 95% CI 0.38-0.96). Ever smokers showed an OR of 1.19 (95% CI 0.92-1.55) compared to never smokers. CONCLUSION: The observed association between lower socioeconomic level and increased odds for uveal melanoma possibly represents a higher occupational uveal melanoma risk for occupational categories that are usually associated with lower socioeconomic status. Concerning having children and uveal melanoma development, we hypothesize that the observed association is mediated through alpha-melanocyte-stimulating hormone, a hormone that increases during pregnancy and is linked to pigmentation alterations in pregnant women. PMID- 24229070 TI - Variability of measurement of retinal vessel diameters. AB - PURPOSE: To examine the effects of various cardiovascular, ocular, and lifestyle factors on retinal vessel diameters over short periods of time. METHODS: Subjects were invited to have photographs of their retina taken at each of three study visits. The same eye was photographed each time. The photographs were digitized and retinal vessel diameters were measured. Measurements from the retinal photographs taken consecutively (at visit 2 and visit 3), and 1, 3, and 4 weeks apart (between visits 1 and 2, 2 and 3, and 1 and 3, respectively) were compared. RESULTS: There were 63 persons who participated in all study visits and had gradable vessel measurements from all five images used in the analysis. Correlations for pairs of study visits were high, and decreased slightly with increasing length of the time interval. For consecutive photographs taken, and 1 week, 3 weeks, and 4 weeks apart, correlations were 0.95, 0.90, 0.91, and 0.86, respectively, for central retinal arteriolar equivalent (CRAE) and 0.95, 0.90, 0.91, and 0.87, respectively, for central retinal venular equivalent (CRVE). We examined the associations of blood pressure levels, smoking habits, time since last eating, exercising, consuming caffeine, and taking anti-hypertensive medication, and image focus with CRAE and CRVE. We found no consistent pattern of association of any of these characteristics with short-term changes in CRAE and CRVE. CONCLUSION: Retinal vessel diameters are stable over short intervals of time and none of the factors studied were consistently associated with change in the diameters of either vessel type. PMID- 24229073 TI - Poly(Epsilon-lysine) dendrons tethered with phosphoserine increase mesenchymal stem cell differentiation potential of calcium phosphate gels. AB - Calcium phosphates (CaP) are considered as biomaterials of choice for the treatment of critical-sized bone defects. Novel injectable CaP materials integrating poly(epsilon-lysine) generation 3 dendrons tethered with phosphoserine were obtained by sol-gel synthesis. This type of dendron was integrated to mimic the biochemical structure of noncollagenous proteins present in the forming osteoids during bone repair. Sol-gel synthesis was coupled with a dialysis process able to equilibrate the materials at a physiological pH value. Fourier transform infrared spectroscopy (FTIR) showed the successful retention of the dendrons after gel dialysis, whereas X-ray diffraction analysis demonstrated both the pH-tuned formation of a hydroxyapatite crystalline phase within the gel and the complete removal of ammonium nitrate deriving from the sol-gel reaction solvent. Scanning electron microscopy images confirmed the presence of crystalline domains in gels synthesized at pH 9.0. Injectability tests showed that the optimized formulations fulfilled the rheological properties required to minimally invasive surgical procedures. Cytotoxicity tests on osteoblast-like MG 63 cells as well as morphology and viability studies showed that the dendrons induced a significantly higher level of cell proliferation at early incubation time. Differentiation of the cell was also clearly enhanced at longer incubation time as demonstrated by both alkaline phosphatase activity and expression of typical markers. Altogether, the data from this work indicate the clinical potential of the osteoid-mimicking CaP cements in minimally invasive bone surgery. PMID- 24229074 TI - Quantitative mass spectrometry independence from matrix effects and detector saturation achieved by flow injection analysis with real-time infinite dilution. AB - A high-throughput quantitative analysis method is presented to determine analyte concentrations at the infinite dilution limit, where the presence and effects of matrix become null, achieving mathematical independence from the detrimental phenomenon of matrix effects. Dilution is achieved online, reproducibly and in seconds by diffusion/mixing that occurs in flow injection analysis, while analyte concentration measurements are made by electrospray ionization tandem mass spectrometry. Because of matrix effects, the measured analyte concentration (Am) was inaccurate at high matrix concentrations, but accuracy consistently improved as matrix concentration was reduced by dilution. The method provides a practical solution around the decades-long matrix effects problem in quantitative analytical chemistry without separation of analytes from the matrix (e.g., chromatography) or use of corrective procedures, such as matrix-matched standards or isotopically labeled internal standards. Broad applications were demonstrated for part-per-billion quantitation of bioactive molecules (pesticides) in extracts of food, plant tissues, and body fluids by coupling the method to a high throughput sample extraction/cleanup based on salting out with ammonium formate. The technique provides an assessment of matrix effects with remarkable comprehensiveness, simplicity, and speed. A limit of quantitation of 10 ng/g, a level appropriate for pesticide residue analysis and bioanalytical applications, was demonstrated. The method is also independent of detector saturation; this feature increased the applicable concentration range 20-100-fold above that of conventional techniques. In the abstract graphic, the measured analyte concentration (Am) approaches the accurate value (A0) when matrix effects disappear as measurements are conducted while lowering the normalized sample concentration (Snorm) by real-time dilution. PMID- 24229075 TI - A comparison and optimization of methods and factors affecting the transformation of Escherichia coli. AB - DNA manipulation routinely requires competent bacteria that can be made using one of numerous methods. To determine the best methods, we compared four commonly used chemical methods (DMSO, MgCl2-CaCl2, CaCl2 and Hanahan's methods) on frequently used Escherichia coli (E. coli) strains: DH5alpha, XL-1 Blue, SCS110, JM109, TOP10 and BL21-(DE3)-PLysS. Hanahan's method was found to be most effective for DH5alpha, XL-1 Blue and JM109 strains (P<0.05), whilst the CaCl2 method was best for SCS110, TOP10 and BL21 strains (P<0.05). The use of SOB (super optimal broth) over LB [Luria-Bertani (broth)] growth media was found to enhance the competency of XL-1 Blue (P<0.05), dampened JM109's competency (P<0.05), and had no effect on the other strains (P>0.05). We found no significant differences between using 45 or 90 s heat shock across all the six strains (P>0.05). Through further optimization by means of concentrating the aliquots, we were able to get further increases in transformation efficiencies. Based on the optimized parameters and methods, these common laboratory E. coli strains attained high levels of TrE (transformation efficiency), thus facilitating the production of highly efficient and cost-effective competent bacteria. PMID- 24229076 TI - A simple mechanical technique to obtain carbon nanoscrolls from graphite nanoplatelets. AB - A simple approach for the bulk production of carbon nanoscrolls (CNSs) is described. This method is based on the application of shear-friction forces to convert graphite nanoplatelets into carbon nanoscrolls using a bi-axially oriented polypropylene (BOPP) surface. The combined action of shear and friction forces causes the exfoliation of graphite nanoplatelets and the simultaneous roll up of graphite layers. Evidence of the CNS formation is given by optical microscopy, scanning electron microscopy, and transmission electron microscopy. These investigations reveal that the CNSs have a long tube-like and fusiform structure with a hollow core surrounded by few layers of graphene. Micro-Raman spectroscopy shows that the produced structures are not defect free, and optical spectroscopy reveals distinctive features due to the presence of two weak absorption bands at 224 and 324 nm. PMID- 24229077 TI - Silyl migrations in D-xylose derivatives: total synthesis of a marine quinoline alkaloid. AB - A versatile method for the synthesis of orthogonally protected D-xylose 1 thioethers is described using unusual silyl group migrations which were pivotal in the synthesis of 4,8-dimethyl-6-O-(2',4'-di-O-methyl-beta-D xylopyranosyl)hydroxyquinoline confirming the structure and absolute configuration of the natural product. PMID- 24229078 TI - Epidemiology of vasomotor rhinitis. AB - Vasomotor rhinitis is the most common form of nonallergic rhinitis, comprising approximately 71% of all nonallergic rhinitis conditions. Although the epidemiology of this subtype of nonallergic rhinitis has not been definitively studied, it is estimated that 14 million Americans suffer from vasomotor rhinitis, with a worldwide prevalence approaching 320 million. PMID- 24229079 TI - A multi-arm multi-stage clinical trial design for binary outcomes with application to tuberculosis. AB - BACKGROUND: Randomised controlled trials are becoming increasingly costly and time-consuming. In 2011, Royston and colleagues proposed a particular class of multi-arm multi-stage (MAMS) designs intended to speed up the evaluation of new treatments in phase II and III clinical trials. Their design, which controls the type I error rate and power for each pairwise comparison, discontinues randomisation to poorly performing arms at interim analyses if they fail to show a pre-specified level of benefit over the control arm. Arms in which randomisation is continued to the final stage of the trial are compared against the control on a definitive time-to-event outcome measure. To increase efficiency, interim comparisons can be made on an intermediate time-to-event outcome which is on the causal pathway to the definitive outcome. METHODS: We adapt Royston's MAMS design to binary outcomes observed at the end of a fixed follow-up period and analysed using an absolute difference in proportions. We apply the design to tuberculosis (TB), an area where many new drugs are in development, and demonstrate how it can greatly accelerate the evaluation of new TB regimens. We use simulations to support the extensions to the methodology and to investigate the amount of bias in the estimated treatment effects of arms in which randomisation is ceased at the first interim analysis and arms which continue to the final stage of the trial. RESULTS: The proposed seamless phase II/III TB trial designs are shown to greatly reduce sample size requirements and trial duration compared to conducting separate phase II and III trials. The bias in the estimated treatment effects for the definitive outcome is shown to be small, especially when treatment selection is based on an intermediate outcome or when a reanalysis is performed at the planned end of the trial after all recruited patients have completed follow-up. CONCLUSIONS: The proposed designs are practical and could be used in a variety of disease areas. They hold considerable promise for speeding up the evaluation of new treatments particularly in TB where many new regimens will soon be available for testing in phase II and phase III trials. PMID- 24229080 TI - Evidence and recommendations to support the use of a novel passive water sampler to quantify antibiotics in wastewaters. AB - A novel passive water sampler (diffusive gradients in thin-films for organics, o DGT) was previously developed and successfully tested in the laboratory, but has not yet been validated in the field. Here, o-DGT samplers were deployed in the influent and effluent of a typical UK wastewater treatment plant (WWTP); the influent was also sampled with a conventional automatic sampler (Auto) and by grab (Grab) sampling. All the samples were analyzed by LC-MS/MS for 40 target antibiotics (including 16 sulfonamides (SAs), 12 fluoroquinolones, 6 macrolides, 2 ionophores, 2 diaminopyimidines, 1 aminocoumarin, and 1 lincosamide). The diffusion coefficients (D) of these antibiotics in o-DGT, measured in the laboratory, ranged from 0.58 * 10(-06) to 6.24 * 10(-06) cm(2) s(-1). The derived surface area normalized sampling rates (RS/A, 0.54-5.74 mL d(-1) cm(-2)) were comparable with those for another passive sampler called POCIS. Fourteen antibiotics were detected in the actively sampled water samples, with 10 of the 14 detected in o-DGT devices deployed for more than 7 days. Most of the antibiotics detected in o-DGT, except sulfapyridine, were continually accumulated by o-DGT for ~10 days. Deployment for 7 days is recommended to integrate ambient concentrations over time, without risks of reaching capacity and significant biofouling. Diffusive boundary layer (DBL) thickness had less effect on the o-DGT measurement than reported for other passive samplers. The comparison between o DGT and Auto and Grab samplings showed that o-DGT was more efficient in terms of cost, time, and labor. This study demonstrates for the first time in a real environment that o-DGT is an effective tool for the routine monitoring of antibiotics in wastewaters and provides a powerful approach to studying their occurrence, fate, and behavior in the environment. PMID- 24229083 TI - DSM-5 and ADHD - an interview with Eric Taylor. AB - In this podcast we talk to Prof Eric Taylor about the changes to the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) in DSM-5 and how these changes will affect clinical practice. The podcast for this interview is available at: http://www.biomedcentral.com/sites/2999/download/Taylor.mp3. PMID- 24229082 TI - Effects of supplementary butyrate on butanol production and the metabolic switch in Clostridium beijerinckii NCIMB 8052: genome-wide transcriptional analysis with RNA-Seq. AB - BACKGROUND: Butanol (n-butanol) has high values as a promising fuel source and chemical feedstock. Biobutanol is usually produced by the solventogenic clostridia through a typical biphasic (acidogenesis and solventogenesis phases) acetone-butanol-ethanol (ABE) fermentation process. It is well known that the acids produced in the acidogenic phase are significant and play important roles in the switch to solventogenesis. However, the mechanism that triggers the metabolic switch is still not clear. RESULTS: Sodium butyrate (40 mM) was supplemented into the medium for the ABE fermentation with Clostridium beijerinckii NCIMB 8052. With butyrate addition (reactor R1), solvent production was triggered early in the mid-exponential phase and completed quickly in < 50 h, while in the control (reactor R2), solventogenesis was initiated during the late exponential phase and took > 90 h to complete. Butyrate supplementation led to 31% improvement in final butanol titer, 58% improvement in sugar-based yield, and 133% improvement in butanol productivity, respectively. The butanol/acetone ratio was 2.4 versus 1.8 in the control, indicating a metabolic shift towards butanol production due to butyrate addition. Genome-wide transcriptional dynamics was investigated with RNA-Seq analysis. In reactor R1, gene expression related to solventogenesis was induced about 10 hours earlier when compared to that in reactor R2. Although the early sporulation genes were induced after the onset of solventogenesis in reactor R1 (mid-exponential phase), the sporulation events were delayed and uncoupled from the solventogenesis. In contrast, in reactor R2, sporulation genes were induced at the onset of solventogenesis, and highly expressed through the solventogenesis phase. The motility genes were generally down-regulated to lower levels prior to stationary phase in both reactors. However, in reactor R2 this took much longer and gene expression was maintained at comparatively higher levels after entering stationary phase. CONCLUSIONS: Supplemented butyrate provided feedback inhibition to butyrate formation and may be re-assimilated through the reversed butyrate formation pathway, thus resulting in an elevated level of intracellular butyryl phosphate, which may act as a phosphate donor to Spo0A and then trigger solventogenesis and sporulation events. High-resolution genome-wide transcriptional analysis with RNA-Seq revealed detailed insights into the biochemical effects of butyrate on solventogenesis related-events at the gene regulation level. PMID- 24229086 TI - Salicylic acid as a tridentate anchoring group for azo-bridged zinc porphyrin in dye-sensitized solar cells. AB - Two series dyes of azo-bridged zinc porphyrins have been devised, synthesized, and performed in dye-sensitized solar cells, in which salicylic acids and azo groups were introduced as a new anchoring group and pi-conjugated bridge via a simple synthetic procedure. The representation of the new dyes has been investigated by optical, photovoltaic, and electrochemical means. The photoelectric conversion efficiency of their DSSC devices has been improved compared with other DSSC devices sensitized by symmetrical porphyrin dyes. The results revealed that tridentate binding modes between salicylic acid and TiO2 nanoparticles could enhance the efficiency of electron injection. The binding modes between salicylic acid and TiO2 nanoparticles may play a crucial role in the photovoltaic performance of DSSCs. PMID- 24229084 TI - Cheek cell fatty acids reflect n-3 PUFA in blood fractions during linseed oil supplementation: a controlled human intervention study. AB - BACKGROUND: Adequate biomarkers for the dietary supply of fatty acids (FA) are FA of adipose tissue and blood fractions. In human studies, invasive sample collection is unpleasant for subjects. In contrast, cheek cell sampling can be considered as a non-invasive alternative to investigate FA status.The aim of this study was to analyze whether cheek cell FA composition reflect the supplementation of alpha-linolenic acid (ALA) using a linseed oil mixture compared to olive oil supplementation. Additionally, it was investigated if cheek cell FA composition correlates with the FA composition of plasma, red blood cells (RBC) and peripheral blood mononuclear cells (PBMC) before and during both interventions. METHODS: During a 10-week randomized, controlled, double-blind human intervention study, 38 subjects provided cheek cell and blood samples. After a two-week run-in period, the test group (n = 23) received 17 g/d of an ALA rich linseed oil mixture, while the control group (n = 15) received 17 g/d of an omega-3 (n-3) polyunsaturated FA (PUFA)-free olive oil. Cheek cells and blood were collected on days 0, 7 and 56 of the 8-week intervention period. RESULTS: Compared to olive oil, the linseed oil intervention increased ALA and also the endogenously converted long-chain n-3 metabolites eicosatetraenoic-, eicosapentaenoic- and docosapentaenoic acid in cheek cells (P <= 0.05). Docosahexaenoic acid remained unchanged. Reflecting the treatment, the n-6/n-3 ratio decreased in the test group. In general, cheek cell FA reflected the changes of FA in blood fractions. Independent of treatment, significant correlations (P <= 0.05) of n-6 PUFA and n-3 PUFA between cheek cells and plasma, RBC and PBMC were found, except for linoleic acid and ALA. CONCLUSIONS: The changes in FA composition of cheek cells confirmed that ALA from linseed oil increased endogenously derived n-3 PUFA in cheek cell lipids. These changes in cheek cells and their correlation to the respective FA in blood fractions indicate the cheek cell FA profile as an adequate non-invasive biomarker for short-term n-3 PUFA intake and metabolism. Therefore, cheek cell FA can be used in human intervention studies or large-scale epidemiological studies, especially for assessment of the n-3 PUFA status. TRIAL REGISTRATION: ClinicalTrials.gov, IDNCT01317290. PMID- 24229087 TI - Phenotypic differentiation between wild and domesticated varieties of Crescentia cujete L. and culturally relevant uses of their fruits as bowls in the Yucatan Peninsula, Mexico. AB - BACKGROUND: Selection criteria are important for analyzing domestication of perennial plant species, which experience a selection pressure throughout several human generations. We analyze the preferred morphological characteristics of Crescentia cujete fruits, which are used as bowls by the Maya of Yucatan, according to the uses they are given and the phenotypic consequences of artificial selection between one wild and three domesticated varieties. METHODS: We performed 40 semi-structured interviews in seven communities. We calculated Sutrop's salience index (S) of five classes of ceremonial and daily life uses, and of each item from the two most salient classes. We sampled 238 bowls at homes of people interviewed and compared their shape, volume and thickness with 139 fruits collected in homegardens and 179 from the wild. Morphology of varieties was assessed in fruit (n = 114 trees) and vegetative characters (n = 136 trees). Differences between varieties were evaluated through linear discriminant analysis (LDA). RESULTS: Use of bowls as containers for the Day of the Dead offerings was the most salient class (S = 0.489) with chocolate as its most salient beverage (S = 0.491), followed by consumption of daily beverages (S = 0.423), especially maize-based pozol (S = 0.412). The sacred saka' and balche' are offered in different sized bowls during agricultural and domestic rituals. Roundness was the most relevant character for these uses, as bowls from households showed a strong selection towards round shapes compared with wild and homegarden fruits. Larger fruits from domesticated varieties were also preferred over small wild fruits, although in the household different sizes of the domesticated varieties are useful. LDA separated wild from domesticated trees (p < 0.001) according to both fruit and vegetative variables, but domesticated varieties were not different among themselves. CONCLUSIONS: The association between C. cujete bowls and traditional beverages in ritual and daily life situations has driven for centuries the selection of preferred fruit morphology in this tree. Selection of fruit roundness and volume has allowed for the differentiation between the wild variety and the three domesticated ones, counteracting gene flow among them. By choosing the best fruits from domesticated varieties propagated in homegardens, the Maya people model the domestication process of this important tree in their culture. PMID- 24229089 TI - Predictors of response to early basal insulin treatment in patients with type 2 diabetes--the EARLY experience. AB - BACKGROUND: It was the aim of this study to assess baseline predictors for glycosylated hemoglobin (HbA1c) reduction, treatment-to-target, and insulin glargine dose in patients with an HbA1c level of >= 7.5% (58 mmol/mol) at baseline despite 3 months of maximum tolerated dose of metformin under daily conditions. SUBJECTS AND METHODS: This was an open, multicenter, prospective observational study with a 6-month follow-up including 1,438 patients with type 2 diabetes. Baseline variables independently associated with HbA1c (overall reduction and achievement of target values) and insulin glargine dose used were determined using a stepwise multivariate linear regression analysis. RESULTS: In a multivariate linear regression analysis (R(2)=0.545) baseline HbA1c (beta= 0.722; P<0.001) and retinopathy (beta=-0.064; P=0.007) were associated with a greater HbA1c reduction at 6 months, whereas duration of diabetes was associated with a lesser HbA1c reduction (beta=0.084; P<0.001). In another multivariate linear regression analysis, weight (odds ratio [OR] 0.99; 95% confidence interval [CI] 0.98 to <1.00), duration of diabetes (OR 0.96; 95% CI 0.93-0.99), and baseline HbA1c (OR 0.65; 95% CI 0.56-0.76) were associated with a reduced likelihood of achieving an HbA1c level of <7% (53 mmol/mol); baseline HbA1c (OR 0.66; 95% CI 0.51-0.85) was the only variable associated with a reduced likelihood of achieving an HbA1c level of <6.5% (48 mmol/mol). In a further analysis (R(2)=0.135) the insulin dose needed was increased in those with a higher body weight (beta=0.230; P<0.001), a longer duration of diabetes (beta=0.134; P<0.001), a higher baseline HbA1c level (beta=0.205; P<0.001), and the presence of microalbuminuria (beta=0.096; P=0.003). CONCLUSIONS: Identified predictors of greater HbA1c reduction, target goal achievement, and insulin dose needed may help to optimize the balance of benefits and risks with the use of insulin glargine. PMID- 24229091 TI - Virus-directed design of a flexible BaTiO3 nanogenerator. AB - Biotemplated synthesis of functional nanomaterials has received increasing attention for applications in energy, catalysis, bioimaging, and other technologies. This approach is justified by the unique abilities of biological systems to guide sophisticated assembly and organization of molecules and materials into distinctive nanoscale morphologies that exhibit physicochemical properties highly desirable for specific purposes. Here, we present a high performance, flexible nanogenerator using anisotropic BaTiO3 (BTO) nanocrystals synthesized on an M13 viral template through the genetically programmed self assembly of metal ion precursors. The filamentous viral template realizes the formation of a highly entangled, well-dispersed network of anisotropic BTO nanostructures with high crystallinity and piezoelectricity. Even without the use of additional structural stabilizers, our virus-enabled flexible nanogenerator exhibits a high electrical output up to ~300 nA and ~6 V, indicating the importance of nanoscale structures for device performances. This study shows the biotemplating approach as a facile method to design and fabricate nanoscale materials particularly suitable for flexible energy harvesting applications. PMID- 24229092 TI - The intersection of interfacial forces and electrochemical reactions. AB - We review recent developments in experimental techniques that simultaneously combine measurements of the interaction forces or energies between two extended surfaces immersed in electrolyte solutions-primarily aqueous-with simultaneous monitoring of their (electro)chemical reactions and controlling the electrochemical surface potential of at least one of the surfaces. Combination of these complementary techniques allows for simultaneous real time monitoring of angstrom level changes in surface thickness and roughness, surface-surface interaction energies, and charge and mass transferred via electrochemical reactions, dissolution, and adsorption, and/or charging of electric double layers. These techniques employ the surface forces apparatus (SFA) combined with various "electrochemical attachments" for in situ measurements of various physical and (electro)chemical properties (e.g., cyclic voltammetry), optical imaging, and electric potentials and currents generated naturally during an interaction, as well as when electric fields (potential differences) are applied between the surfaces and/or solution-in some cases allowing for the chemical reaction equation to be unambiguously determined. We discuss how the physical interactions between two different surfaces when brought close to each other (<10 nm) can affect their chemistry, and suggest further extensions of these techniques to biological systems and simultaneous in situ spectroscopic measurements for chemical analysis. PMID- 24229093 TI - Nature versus nurture: predictability in low-temperature Ising dynamics. AB - Consider a dynamical many-body system with a random initial state subsequently evolving through stochastic dynamics. What is the relative importance of the initial state ("nature") versus the realization of the stochastic dynamics ("nurture") in predicting the final state? We examined this question for the two dimensional Ising ferromagnet following an initial deep quench from T=infinity to T=0. We performed Monte Carlo studies on the overlap between "identical twins" raised in independent dynamical environments, up to size L=500. Our results suggest an overlap decaying with time as t(-theta)(h) with theta(h)=0.22 +/- 0.02; the same exponent holds for a quench to low but nonzero temperature. This "heritability exponent" may equal the persistence exponent for the two dimensional Ising ferromagnet, but the two differ more generally. PMID- 24229090 TI - The link between chronic periodontitis and COPD: a common role for the neutrophil? AB - BACKGROUND: The possible relationship between chronic inflammatory diseases and their co-morbidities has become an increasing focus of research. Both chronic periodontitis and chronic obstructive pulmonary disease are neutrophilic, inflammatory conditions characterized by the loss of local connective tissue. Evidence suggests an association and perhaps a causal link between the two diseases. However, the nature of any relationship between them is unclear, but if pathophysiologically established may have wide-reaching implications for targeted treatments to improve outcomes and prognosis. DISCUSSION: There have been a number of epidemiological studies undertaken demonstrating an independent association between chronic periodontitis and chronic obstructive pulmonary disease. However, many of them have significant limitations, and drawing firm conclusions regarding causality may be premature. Although the pathology of both these diseases is complex and involves many cell types, such as CD8 positive cells and macrophages, both conditions are predominantly characterized by neutrophilic inflammation. Increasingly, there is evidence that the two conditions are underpinned by similar pathophysiological processes, especially centered on the functions of the neutrophil. These include a disturbance in protease/anti-protease and redox state balance. The association demonstrated by epidemiological studies, as well as emerging similarities in pathogenesis at the level of the neutrophil, suggest a basis for testing the effects of treatment for one condition upon the severity of the other. SUMMARY: Although the evidence of an independent association between chronic periodontitis and chronic obstructive pulmonary disease grows stronger, there remains a lack of definitive studies designed to establish causality and treatment effects. There is a need for future research to be focused on answering these questions. PMID- 24229094 TI - Intrinsic noise and discrete-time processes. AB - A general formalism is developed to construct a Markov chain model that converges to a one-dimensional map in the infinite population limit. Stochastic fluctuations are therefore internal to the system and not externally specified. For finite populations an approximate Gaussian scheme is devised to describe the stochastic fluctuations in the nonchaotic regime. More generally, the stochastic dynamics can be captured using a stochastic difference equation, derived through an approximation to the Markov chain. The scheme is demonstrated using the logistic map as a case study. PMID- 24229095 TI - Onset of flow in a confined colloidal glass under an imposed shear stress. AB - A confined colloidal glass, under the imposition of a uniform shear stress, is investigated using numerical simulations. Both at macro- and microscales, the consequent dynamics during the onset of flow is studied. When the imposed stress is gradually decreased, the time scale for the onset of steady flow diverges, associated with long-lived spatial heterogeneities. Near this yield-stress regime, persistent creep in the form of shear-banded structures is observed. PMID- 24229096 TI - Periodic structures in binary mixtures enforced by Janus particles. AB - Phase separation in binary mixtures in the presence of Janus particles has been studied in terms of a Cahn-Hilliard model coupled to the Langevin equations describing the particle dynamics. We demonstrate that the phase separation process is arrested leading to unexpected regular stripe patterns in the concentration field. The underlying pattern forming mechanism has been elucidated: The twofold absorption properties on the surface of Janus particles with respect to the two components of a binary mixture trigger in their neighborhood spatial concentration variations. They result in an effective interaction between the particles mediated by the binary mixture. Our findings open a route to design composite materials with nanoscale lamellar morphologies where the pattern wavelength can be tuned by changing the wetting properties of the Janus particles. PMID- 24229097 TI - Invasion-wave-induced first-order phase transition in systems of active particles. AB - An instability near the transition to collective motion of self-propelled particles is studied numerically by Enskog-like kinetic theory. While hydrodynamics breaks down, the kinetic approach leads to steep solitonlike waves. These supersonic waves show hysteresis and lead to an abrupt jump of the global order parameter if the noise level is changed. Thus they provide a mean-field mechanism to change the second-order character of the phase transition to first order. The shape of the wave is shown to follow a scaling law and to quantitatively agree with agent-based simulations. PMID- 24229098 TI - Optomechanical elastomeric engine. AB - Nematic elastomers contract along their director when heated or illuminated (in the case of photoelastomers). We present a conceptual design for an elastomer based engine to extract mechanical work from heat or light. The material parameters and the geometry of such an engine are explored, and it is shown that its efficiency can go up to 20%. PMID- 24229099 TI - Giant and universal magnetoelectric coupling in soft materials and concomitant ramifications for materials science and biology. AB - Magnetoelectric coupling-the ability of a material to magnetize upon application of an electric field and, conversely, to polarize under the action of a magnetic field-is rare and restricted to a rather small set of exotic hard crystalline materials. Intense research activity has recently ensued on materials development, fundamental scientific issues, and applications related to this phenomenon. This tantalizing property, if present in adequate strength at room temperature, can be used to pave the way for next-generation memory devices such as miniature magnetic random access memories and multiple state memory bits, sensors, energy harvesting, spintronics, among others. In this Rapid Communication, we prove the existence of an overlooked strain mediated nonlinear mechanism that can be used to universally induce the giant magnetoelectric effect in all (sufficiently) soft dielectric materials. For soft polymer foams-which, for instance, may be used in stretchable electronics-we predict room-temperature magnetoelectric coefficients that are comparable to the best known (hard) composite materials created. We also argue, based on a simple quantitative model, that magnetoreception in some biological contexts (e.g., birds) most likely utilizes this very mechanism. PMID- 24229100 TI - Hydrodynamic and subdiffusive motion of tracers in a viscoelastic medium. AB - We investigate the diffusive motion of micron-sized spherical tracers in a viscoelastic actin filament network over the time span of 8 orders of magnitude using optical-tweezers single-particle tracking. The hydrodynamic interactions of a tracer with the surrounding fluid are shown to dominate at microsecond time scales, while subdiffusive scaling due to viscoelastic properties of the medium emerges at millisecond time scales. The transition between these two regimes is analyzed in the frame of a minimal phenomenological model which combines the Basset force and the generalized Stokes force. The resulting Langevin equation accounts for various dynamical features of the thermal motion of endogenous or exogenous tracers in viscoelastic media such as inertial and hydrodynamic effects at short times, subdiffusive scaling at intermediate times, and eventual optical trapping at long times. Simple analytical formulas for the mean-square displacement and velocity autocorrelation function are derived. PMID- 24229101 TI - Energy landscape and dynamics of proteins: an exact analysis of a simplified lattice model. AB - We present the results of exact numerical studies of the energy landscape and the dynamics of a 12-monomer chain with contact interactions encoding the ground state on a square lattice. In spite of its simplicity, the model is shown to exhibit behavior at odds with the standard picture of proteins. PMID- 24229102 TI - Binding-rebinding dynamics of proteins interacting nonspecifically with a long DNA molecule. AB - We investigate how nonspecific interactions and unbinding-rebinding events give rise to a length- and conformation-dependent enhancement of the "macroscopic" dissociation time of proteins from a DNA, or in general for the release of ligands initially bound to a long polymer. By numerically simulating the release of ligands from polymers of different conformations, we show that the total dissociation time increases logarithmically with polymer length for an extended conformation, and as a power law for self-avoiding and compact conformations. For the latter two cases, the presence of self-avoidance acting between the diffusing ligands affects the power-law exponents. Our results are important in relating kinetic measurements of protein on- and off-rates for large DNAs to equilibrium affinities for a single binding site. PMID- 24229103 TI - Endemic infections are always possible on regular networks. AB - We study the dependence of the largest component in regular networks on the clustering coefficient, showing that its size changes smoothly without undergoing a phase transition. We explain this behavior via an analytical approach based on the network structure, and provide an exact equation describing the numerical results. Our work indicates that intrinsic structural properties always allow the spread of epidemics on regular networks. PMID- 24229104 TI - Supratransmission induced by waves collisions in a discrete electrical lattice. AB - We numerically performed a way to produce a supratransmission phenomenon in the Salerno equation describing the dynamics of modulated waves in a discrete nonlinear transmission lattice. For the natural supratransmission phenomenon, there exists a threshold of amplitude for which energy can flow in the line. We show that gap transmission is possible with driven amplitude below the threshold due to the collision of different plane waves coming from both edges of the line. One of the two plane waves has a frequency in the forbidden gap, and another has a frequency in the allowed phonon band. During collision, the wave in the allowed band is considered as a perturbation of the ones in the forbidden gap. PMID- 24229105 TI - Decomposing the dynamics of heterogeneous delayed networks with applications to connected vehicle systems. AB - Delay-coupled networks are investigated with nonidentical delay times and the effects of such heterogeneity on the emergent dynamics of complex systems are characterized. A simple decomposition method is presented that decouples the dynamics of the network into node-size modal equations in the vicinity of equilibria. The resulting independent components contain distributed delays that map the spatiotemporal complexity of the system to the time domain. We demonstrate that this approach can be used to reveal physical phenomena in heterogenous vehicular traffic when vehicles are linked via vehicle-to-vehicle communication. PMID- 24229106 TI - Quorum sensing via static coupling demonstrated by Chua's circuits. AB - Dynamical quorum sensing, the population based phenomenon, is believed to occur when the elements of a system interact via dynamic coupling. In the present work, we demonstrate an alternate scenario, involving static coupling, that could also lead to quorum sensing behavior. These static and dynamic coupling terms have already been employed by Konishi [Int. J. Bifurcation Chaos Appl. Sci. Eng. 17, 2781 (2007)]. In our context, the coupling is defined as static or dynamic, on the basis of the relative time scales at which the surrounding dynamics and the elements' dynamics evolve. According to this, if the variation in the surrounding dynamics happens on a much larger (fast) time scale than that at which the elements' dynamics are varying (such as seconds and MUs), then the coupling is considered to be static, otherwise it is considered to be dynamic. A series of experiments have been performed starting from a system of three Chua's circuits to a system of 20 Chua's circuits to study two types of quorum transitions: the emergence and the extinction of global oscillations (period-1). The numerics involving up to 100 Chua's circuits validate the experimental observations. PMID- 24229107 TI - Diffusion approximation in turbulent two-particle dispersion. AB - We solve an inverse problem for fluid particle pair statistics: we show that a time sequence of probability density functions (PDFs) of separations can be exactly reproduced by solving the diffusion equation with a suitable time dependent diffusivity. The diffusivity tensor is given by a time integral of a conditional Lagrangian velocity structure function, weighted by a ratio of PDFs. Physical hypotheses for hydrodynamic turbulence (sweeping, short memory, mean field) yield simpler integral formulas, including one of Kraichnan and Lundgren (K-L). We evaluate the latter using a space-time database from a numerical Navier Stokes solution for driven turbulence. The K-L formula reproduces PDFs well at root-mean-square separations, but growth rate of mean-square dispersion is overpredicted due to neglect of memory effects. More general applications of our approach are sketched. PMID- 24229108 TI - Enhanced diffusion of nonswimmers in a three-dimensional bath of motile bacteria. AB - We show, using differential dynamic microscopy, that the diffusivity of nonmotile cells in a three-dimensional (3D) population of motile E. coli is enhanced by an amount proportional to the active cell flux. While nonmotile mutants without flagella and mutants with paralyzed flagella have quite different thermal diffusivities and therefore hydrodynamic radii, their diffusivities are enhanced to the same extent by swimmers in the regime of cell densities explored here. Integrating the advective motion of nonswimmers caused by swimmers with finite persistence-length trajectories predicts our observations to within 2%, indicating that fluid entrainment is not relevant for diffusion enhancement in 3D. PMID- 24229109 TI - Scaling laws for ignition at the National Ignition Facility from first principles. AB - We have developed an analytical physics model from fundamental physics principles and used the reduced one-dimensional model to derive a thermonuclear ignition criterion and implosion energy scaling laws applicable to inertial confinement fusion capsules. The scaling laws relate the fuel pressure and the minimum implosion energy required for ignition to the peak implosion velocity and the equation of state of the pusher and the hot fuel. When a specific low-entropy adiabat path is used for the cold fuel, our scaling laws recover the ignition threshold factor dependence on the implosion velocity, but when a high-entropy adiabat path is chosen, the model agrees with recent measurements. PMID- 24229110 TI - Wigner distribution functions for complex dynamical systems: the emergence of the Wigner-Boltzmann equation. AB - The equation of motion for the reduced Wigner function of a system coupled to an external quantum system is presented for the specific case when the external quantum system can be modeled as a set of harmonic oscillators. The result is derived from the Wigner function formulation of the Feynman-Vernon influence functional theory. It is shown how the true self-energy for the equation of motion is connected with the influence functional for the path integral. Explicit expressions are derived in terms of the bare Wigner propagator. Finally, we show under which approximations the resulting equation of motion reduces to the Wigner Boltzmann equation. PMID- 24229111 TI - High-precision Monte Carlo study of directed percolation in (d+1) dimensions. AB - We present a Monte Carlo study of the bond- and site-directed (oriented) percolation models in (d+1) dimensions on simple-cubic and body-centered-cubic lattices, with 2 <= d <= 7. A dimensionless ratio is defined, and an analysis of its finite-size scaling produces improved estimates of percolation thresholds. We also report improved estimates for the standard critical exponents. In addition, we study the probability distributions of the number of wet sites and radius of gyration, for 1 <= d <= 7. PMID- 24229112 TI - Effect of short-range order on transport in one-particle tight-binding models. AB - We investigate transport properties of topologically disordered three-dimensional one-particle tight-binding models, featuring site-distance-dependent hopping terms. We start from entirely disordered systems into which we gradually introduce some short-range order by numerically performing a pertinent structural relaxation using local site-pair interactions. Transport properties of the resulting models within the delocalized regime are analyzed numerically using linear response theory. We find that even though the generated order is very short ranged, transport properties such as conductivity or mean free path scale significantly with the degree of order. Mean free paths may exceed the site-pair correlation length. It is furthermore demonstrated that while the totally disordered model is not in accord with a Drude- or Boltzmann-type description, moderate degrees of order suffice to render such a picture valid. PMID- 24229113 TI - Role of network junctions for the totally asymmetric simple exclusion process. AB - We study the effect of local regulation mechanisms on stochastic network traffic, based on simple examples. Using the totally asymmetric simple exclusion process on a multiloop structure in which several segments share a single junction, we illustrate several mechanisms: (i) additional segments improve transport but the effect saturates due to blockage, (ii) bias reduces the overall transport and leads to several regimes, (iii) "pumping" particles out of the junctions, via a locally increased hopping rate, allows us to compensate the bottlenecks but becomes futile beyond a characteristic rate which we determine. We provide a generic discussion of combinations of these effects, including phase diagrams in terms of the control parameters. PMID- 24229114 TI - Backbone structure of the Edwards-Anderson spin-glass model. AB - We study the ground-state spatial heterogeneities of the Edwards-Anderson spin glass model with both bimodal and Gaussian bond distributions. We characterize these heterogeneities by using a general definition of bond rigidity, which allows us to classify the bonds of the system into two sets, the backbone and its complement, with very different properties. This generalizes to continuous distributions of bonds the well-known definition of a backbone for discrete bond distributions. By extensive numerical simulations we find that the topological structure of the backbone for a given lattice dimensionality is very similar for both discrete and continuous bond distributions. We then analyze how these heterogeneities influence the equilibrium properties at finite temperature and we discuss the possibility that a suitable backbone picture can be relevant to describe spin-glass phenomena. PMID- 24229115 TI - Phases and fluctuations in a model for asymmetric inhomogeneous fluid membranes. AB - We propose and analyze a model for phase transitions in an inhomogeneous fluid membrane, that couples local composition with curvature nonlinearly. For asymmetric membranes, our model shows generic non-Ising behavior and the ensuing phase diagram displays either a first- or a second-order phase transition through a critical point (CP) or a tricritical point (TP), depending upon the bending modulus. It predicts generic nontrivial enhancement in fluctuations of asymmetric membranes that scales with system size in a power-law fashion at the CP and TP in two dimensions, not observed in symmetric membranes. It also yields two dimensional Ising universality class for symmetric membranes, in agreement with experimental results. PMID- 24229116 TI - Heat capacity singularity of binary liquid mixtures at the liquid-liquid critical point. AB - The critical anomaly of the isobaric molar heat capacity for the liquid-liquid phase transition in binary nonionic mixtures is explained through a theory based on the general assumption that their partition function can be exactly mapped into that of the Ising three-dimensional model. Under this approximation, it is found that the heat capacity singularity is directly linked to molar excess enthalpy. In order to check this prediction and complete the available data for such systems, isobaric molar heat capacity and molar excess enthalpy near the liquid-liquid critical point were experimentally determined for a large set of binary liquid mixtures. Agreement between theory and experimental results-both from literature and from present work-is good for most cases. This fact opens a way for explaining and predicting the heat capacity divergence at the liquid liquid critical point through basically the same microscopic arguments as for molar excess enthalpy, widely used in the frame of solution thermodynamics. PMID- 24229117 TI - Modified Bose-Einstein and Fermi-Dirac statistics if excitations are localized on an intermediate length scale: applications to non-Debye specific heat. AB - Disordered systems show deviations from the standard Debye theory of specific heat at low temperatures. These deviations are often attributed to two-level systems of uncertain origin. We find that a source of excess specific heat comes from correlations between quanta of energy if excitations are localized on an intermediate length scale. We use simulations of a simplified Creutz model for a system of Ising-like spins coupled to a thermal bath of Einstein-like oscillators. One feature of this model is that energy is quantized in both the system and its bath, ensuring conservation of energy at every step. Another feature is that the exact entropies of both the system and its bath are known at every step, so that their temperatures can be determined independently. We find that there is a mismatch in canonical temperature between the system and its bath. In addition to the usual finite-size effects in the Bose-Einstein and Fermi Dirac distributions, if excitations in the heat bath are localized on an intermediate length scale, this mismatch is independent of system size up to at least 10(6) particles. We use a model for correlations between quanta of energy to adjust the statistical distributions and yield a thermodynamically consistent temperature. The model includes a chemical potential for units of energy, as is often used for other types of particles that are quantized and conserved. Experimental evidence for this model comes from its ability to characterize the excess specific heat of imperfect crystals at low temperatures. PMID- 24229118 TI - Work distribution and edge singularities for generic time-dependent protocols in extended systems. AB - We study the statistics of the work done by globally changing in time with a generic protocol the mass in a free bosonic field theory with relativistic dispersion and the transverse field in the one-dimensional Ising chain both globally and locally. In the latter case we make the system start from the critical point and we describe it in the scaling limit. We provide exact formulas in all these cases for the full statistics of the work and we show that the low energy part of the distribution of the work displays an edge singularity whose exponent does not depend on the specifics of the protocol that is chosen and may only depend on the position of the initial and final values with respect to the critical point of the system. We also show that the condensation transition found in the bosonic system for sudden quenches [A. Gambassi and A. Silva, Phys. Rev. Lett. 109, 250602 (2012)] is robust with respect to the choice of the protocol. PMID- 24229119 TI - Mesoscopic hydrothermodynamics of complex-structured materials. AB - Some experimental results in the study of disordered systems, polymeric fluids, solutions of micelles and surfactants, ionic-glass conductors, and others show a hydrodynamic behavior labeled "anomalous" with properties described by some kind of fractional power laws in place of the standard ones. This is a consequence of the fractal-like structure that is present in these systems of which we do not have a detailed description, thus impairing the application of the conventional ensemble formalism of statistical mechanics. In order to obtain a physical picture of the phenomenon for making predictions which may help with technological and industrial decisions, one may resort to different styles (so called nonconventional) in statistical mechanics. In that way can be introduced a theory for handling such impaired situations, a nonconventional mesoscopic hydrothermodynamics (MHT). We illustrate the question presenting an application in a contracted description of such nonconventional MHT, consisting in the use of the Renyi approach to derive a set of coupled nonstandard evolution equations, one for the density, a nonconventional Maxwell-Cattaneo equation, which in a limiting case goes over a non-Fickian diffusion equation, and other for the velocity in fluids under forced flow. For illustration the theory is applied to the study of the hydrodynamic motion in several soft-matter systems under several conditions such as streaming flow appearing in electrophoretic techniques and flow generated by harmonic forces arising in optical traps. The equivalence with Levy processes is discussed and comparison with experiment is done. PMID- 24229120 TI - Stochastic kinetics of photoinduced phase transitions in spin-crossover solids. AB - We study the stochastic macroscopic kinetics of photoinduced phase transitions in spin-crossover compounds assisted by white and colored Ornstein-Uhlenbeck noise. By using a phenomenological master equation obtained in the mean-field approach, the phase diagram is constructed based on the associated Lyapunov function. The stochastic behavior is then analyzed in the Langevin framework and the corresponding Fokker-Planck equations. Both additive and multiplicative and white and colored types of noise are considered and the stationary probability densities are found along with the noise-assisted light induced hysteretic loops. By using the Kramers formalism, we also focus our attention on the escape time problem in these noise perturbed systems. A detailed study of the relative escape time dependence on various noise characteristics is performed and the main features are compared for different types of noise. PMID- 24229121 TI - Self-organized dynamics in local load-sharing fiber bundle models. AB - We study the dynamics of a local load-sharing fiber bundle model in two dimensions under an external load (which increases with time at a fixed slow rate) applied at a single point. Due to the local load-sharing nature, the redistributed load remains localized along the boundary of the broken patch. The system then goes to a self-organized state with a stationary average value of load per fiber along the (increasing) boundary of the broken patch (damaged region) and a scale-free distribution of avalanche sizes and other related quantities are observed. In particular, when the load redistribution is only among nearest surviving fiber(s), the numerical estimates of the exponent values are comparable with those of the Manna model. When the load redistribution is uniform along the patch boundary, the model shows a simple mean-field limit of this self-organizing critical behavior, for which we give analytical estimates of the saturation load per fiber values and avalanche size distribution exponent. These are in good agreement with numerical simulation results. PMID- 24229122 TI - Random walks in nonuniform environments with local dynamic interactions. AB - We consider a class of lattice random walk models in which the random walker is initially confined to a finite connected set of allowed sites but has the opportunity to enlarge this set by colliding with its boundaries, each such collision having a given probability of breaking through. The model is motivated by an analogy to cell motility in tissue, where motile cells have the ability to remodel extracellular matrix, but is presented here as a generic model for stochastic erosion. For the one-dimensional case, we report some exact analytic results, some mean-field type analytic approximate results and simulations. We compute exactly the mean and variance of the time taken to enlarge the interval from a single site to a given size. The problem of determining the statistics of the interval length and the walker's position at a given time is more difficult and we report several interesting observations from simulations. Our simulations include the case in which the initial interval length is random and the case in which the initial state of the lattice is a random mixture of allowed and forbidden sites, with the walker placed at random on an allowed site. To illustrate the extension of these ideas to higher-dimensional systems, we consider the erosion of the simple cubic lattice commencing from a single site and report simulations of measures of cluster size and shape and the mean-square displacement of the walker. PMID- 24229123 TI - Energy transfer in a molecular motor in the Kramers regime. AB - We present a theoretical treatment of energy transfer in a molecular motor described in terms of overdamped Brownian motion on a multidimensional tilted periodic potential. The tilt represents a thermodynamic force driving the system out of equilibrium and, for nonseparable potentials, energy transfer occurs between degrees of freedom. For deep potential wells, the continuous theory transforms to a discrete master equation that is tractable analytically. We use this master equation to derive formal expressions for the hopping rates, drift and diffusion, and the efficiency and rate of energy transfer in terms of the thermodynamic force. These results span both strong and weak coupling between degrees of freedom, describe the near and far from equilibrium regimes, and are consistent with generalized detailed balance and the Onsager relations. We thereby derive a number of diverse results for molecular motors within a single theoretical framework. PMID- 24229124 TI - Entropy-generated power and its efficiency. AB - We propose a simple and analytically solvable model for a motor that generates mechanical motion by exploiting an entropic force arising from the topology of the underlying phase space. We show that the generation of mechanical forces in our system is surprisingly robust to local changes in kinetic and topological parameters. Furthermore, we find that the efficiency at maximum power of the motor may show discontinuities. PMID- 24229125 TI - Localization-delocalization transition of the instantaneous normal modes of liquid water. AB - Despite the fact that the localization-delocalization transition (LDT) widely exists in wave systems, quantitative studies on its critical and multifractal properties are mainly focused on solids. In this work, these properties are investigated on the vibrational motions of liquid water. Simulations of up to 18000 molecules on the flexible extended simple point charge water model provide nearly 10(6) instantaneous normal modes. They are shown to undergo an LDT close to the translational transition and exhibit multifractal fluctuations while approaching the LDT. In combination with finite-size scaling, multifractal analysis predicts the critical frequency Im(omega(c))~-131.6 cm(-1) for unstable modes at room temperature. The estimated critical exponent nu~1.60 is close to those of other calculated systems in the same Wigner-Dyson class. At the LDT, the fractal spectrum f(alpha) and the most probable local vibrational intensity alpha(mc)~4.04 coincide with those of the Anderson model, which might be additional universal properties of LDT in more general wave systems. The results extend the validity of the multifractal scaling approach beyond Andersonian systems to a Hessian system. PMID- 24229126 TI - Critical properties of the Hintermann-Merlini model. AB - Many critical properties of the Hintermann-Merlini model are known exactly through the mapping to the eight-vertex model. Wu [J. Phys. C 8, 2262 (1975)] calculated the spontaneous magnetizations of the model on two sublattices by relating them to the conjectured spontaneous magnetization and polarization of the eight-vertex model, respectively. The latter conjecture remains unproved. In this paper we numerically study the critical properties of the model by means of a finite-size scaling analysis based on transfer matrix calculations and Monte Carlo simulations. All analytic predictions for the model are confirmed by our numerical results. The central charge c=1 is found for the critical manifold investigated. In addition, some unpredicted geometric properties of the model are studied. Fractal dimensions of the largest Ising clusters on two sublattices are determined. The fractal dimension of the largest Ising cluster on the sublattice A takes a fixed value D(a)=1.888(2), while that for sublattice B varies continuously with the parameters of the model. PMID- 24229127 TI - Extremal paths, the stochastic heat equation, and the three-dimensional Kardar Parisi-Zhang universality class. AB - Following our numerical work [Phys. Rev. Lett. 109, 170602 (2012)] focused upon the 2+1 Kardar-Parisi-Zhang (KPZ) equation with flat initial condition, we return here to study, in depth, the three-dimensional (3D) radial KPZ problem, comparing common scaling phenomena exhibited by the pt-pt directed polymer in a random medium (DPRM), the stochastic heat equation (SHE) with multiplicative noise in three dimensions, and kinetic roughening phenomena associated with 3D Eden clusters. Examining variants of the 3D DPRM, as well as numerically integrating, via the Ito prescription, the constrained SHE for different values of the KPZ coupling, we provide strong evidence for universality within this 3D KPZ class, revealing shared values for the limit distribution skewness and kurtosis, along with universal first and second moments. Our numerical analysis of the 3D SHE, well flanked by the DPRM results, appears without precedent in the literature. We consider, too, the 2+1 KPZ equation in the deeply evolved kinetically roughened stationary state, extracting the essential limit distribution characterizing fluctuations therein, revealing a higher-dimensional relative of the 1+1 KPZ Baik Rains distribution. Complementary, corroborative findings are provided via the Gaussian DPRM, as well as the restricted-solid-on-solid model of stochastic growth, stalwart members of the 2+1 KPZ class. Next, contact is made with a recent nonperturbative, field-theoretic renormalization group calculation for the key universal amplitude ratio in this context. Finally, in the crossover from transient to stationary-state statistics, we observe a higher dimensional manifestation of the skewness minimum discovered by Takeuchi [Phys. Rev. Lett. 110, 210604 (2013)] in 1+1 KPZ class liquid-crystal experiments. PMID- 24229128 TI - Frequency-dependent effective hydraulic conductivity of strongly heterogeneous media. AB - The determination of the transport properties of heterogeneous porous rocks, such as an effective hydraulic conductivity, arises in a range of geoscience problems, from groundwater flow analysis to hydrocarbon reservoir modeling. In the presence of formation-scale heterogeneities, nonstationary flows, induced by pumping tests or propagating elastic waves, entail localized pressure diffusion processes with a characteristic frequency depending on the pressure diffusivity and size of the heterogeneity. Then, on a macroscale, a homogeneous equivalent medium exists, which has a frequency-dependent effective conductivity. The frequency dependence of the conductivity can be analyzed with Biot's equations of poroelasticity. In the quasistatic frequency regime of this framework, the slow compressional wave is a proxy for pressure diffusion processes. This slow compressional wave is associated with the out-of-phase motion of the fluid and solid phase, thereby creating a relative fluid-solid displacement vector field. Decoupling of the poroelasticity equations gives a diffusion equation for the fluid-solid displacement field valid in a poroelastic medium with spatial fluctuations in hydraulic conductivity. Then, an effective conductivity is found by a Green's function approach followed by a strong-contrast perturbation theory suggested earlier in the context of random dielectrics. This theory leads to closed-form expressions for the frequency-dependent effective conductivity as a function of the one- and two-point probability functions of the conductivity fluctuations. In one dimension, these expressions are consistent with exact solutions in both low- and high-frequency limits for arbitrary conductivity contrast. In 3D, the low frequency limit depends on the details of the microstructure. However, the derived approximation for the effective conductivity is consistent with the Hashin-Shtrikman bounds. PMID- 24229129 TI - Asymmetric exclusion process with global hopping. AB - We study a one-dimensional totally asymmetric simple exclusion process with one special site from which particles fly to any empty site (not just to the neighboring site). The system attains a nontrivial stationary state with a density profile varying over the spatial extent of the system. The density profile undergoes a nonequilibrium phase transition when the average density passes through the critical value 1-[4(1-ln2)](-1)=0.185277..., viz., in addition to the discontinuity in the vicinity of the special site, a shock wave is formed in the bulk of the system when the density exceeds the critical density. PMID- 24229130 TI - Effects of the interplay between initial state and Hamiltonian on the thermalization of isolated quantum many-body systems. AB - We explore the role of the initial state on the onset of thermalization in isolated quantum many-body systems after a quench. The initial state is an eigenstate of an initial Hamiltonian H(I) and it evolves according to a different final Hamiltonian H(F). If the initial state has a chaotic structure with respect to H(F), i.e., if it fills the energy shell ergodically, thermalization is certain to occur. This happens when H(I) is a full random matrix, because its states projected onto H(F), are fully delocalized. The results for the observables then agree with those obtained with thermal states at infinite temperature. However, finite real systems with few-body interactions, as the ones considered here, are deprived of fully extended eigenstates, even when described by a nonintegrable Hamiltonian. We examine how the initial state delocalizes as it gets closer to the middle of the spectrum of H(F), causing the observables to approach thermal averages, be the models integrable or chaotic. Our numerical studies are based on initial states with energies that cover the entire lower half of the spectrum of one-dimensional Heisenberg spin-1/2 systems. PMID- 24229131 TI - Percolation model with continuously varying exponents. AB - This work analyzes a percolation model on the diamond hierarchical lattice (DHL), where the percolation transition is retarded by the inclusion of a probability of erasing specific connected structures. It has been inspired by the recent interest on the existence of other universality classes of percolation models. The exact scale invariance and renormalization properties of DHL leads to recurrence maps, from which analytical expressions for the critical exponents and precise numerical results in the limit of very large lattices can be derived. The critical exponents nu and beta of the investigated model vary continuously as the erasing probability changes. An adequate choice of the erasing probability leads to the result nu=infinity, like in some phase transitions involving vortex formation. The percolation transition is continuous, with beta>0, but beta can be as small as desired. The modified percolation model turns out to be equivalent to the Q->1 limit of a Potts model with specific long range interactions on the same lattice. PMID- 24229132 TI - Velocity statistics for interacting edge dislocations in one dimension from Dyson's Coulomb gas model. AB - The dynamics of edge dislocations with parallel Burgers vectors, moving in the same slip plane, is mapped onto Dyson's model of a two-dimensional Coulomb gas confined in one dimension. We show that the tail distribution of the velocity of dislocations is power law in form, as a consequence of the pair interaction of nearest neighbors in one dimension. In two dimensions, we show the presence of a pairing phase transition in a system of interacting dislocations with parallel Burgers vectors. The scaling exponent of the velocity distribution at effective temperatures well below this pairing transition temperature can be derived from the nearest-neighbor interaction, while near the transition temperature, the distribution deviates from the form predicted by the nearest-neighbor interaction, suggesting the presence of collective effects. PMID- 24229133 TI - Log-normal distribution from a process that is not multiplicative but is additive. AB - The central limit theorem ensures that a sum of random variables tends to a Gaussian distribution as their total number tends to infinity. However, for a class of positive random variables, we find that the sum tends faster to a log normal distribution. Although the sum tends eventually to a Gaussian distribution, the distribution of the sum is always close to a log-normal distribution rather than to any Gaussian distribution if the summands are numerous enough. This is in contrast to the current consensus that any log-normal distribution is due to a product of random variables, i.e., a multiplicative process, or equivalently to nonlinearity of the system. In fact, the log-normal distribution is also observable for a sum, i.e., an additive process that is typical of linear systems. We show conditions for such a sum, an analytical example, and an application to random scalar fields such as those of turbulence. PMID- 24229134 TI - Third-order phase transition in random tilings. AB - We consider the domino tilings of an Aztec diamond with a cut-off corner of macroscopic square shape and given size and address the bulk properties of tilings as the size is varied. We observe that the free energy exhibits a third order phase transition when the cut-off square, increasing in size, reaches the arctic ellipse-the phase separation curve of the original (unmodified) Aztec diamond. We obtain this result by studying the thermodynamic limit of a certain nonlocal correlation function of the underlying six-vertex model with domain wall boundary conditions, the so-called emptiness formation probability (EFP). We consider EFP in two different representations: as a tau function for Toda chains and as a random matrix model integral. The latter has a discrete measure and a linear potential with hard walls; the observed phase transition shares properties with both Gross-Witten-Wadia and Douglas-Kazakov phase transitions. PMID- 24229135 TI - Tsallis power laws and finite baths with negative heat capacity. AB - It is often stated that heat baths with finite degrees of freedom i.e., finite baths, are sources of Tsallis distributions for classical Hamiltonian systems. By using well-known fundamental statistical mechanics expressions, we rigorously show that Tsallis distributions with fat tails are possible only for finite baths with constant negative heat capacity, while constant positive heat capacity finite baths yield decays with sharp cutoff with no fat tails. However, the correspondence between Tsallis distributions and finite baths holds at the expense of violating the equipartition theorem for finite classical systems at equilibrium. We comment on the implications of the finite bath for the recent attempts towards a q-generalized central limit theorem. PMID- 24229136 TI - Interplay between finite resources and a local defect in an asymmetric simple exclusion process. AB - When particle flux is regulated by multiple factors such as particle supply and varying transport rate, it is important to identify the respective dominant regimes. We extend the well-studied totally asymmetric simple exclusion model to investigate the interplay between a controlled entrance and a local defect site. The model mimics cellular transport phenomena where there is typically a finite particle pool and nonuniform moving rates due to biochemical kinetics. Our simulations reveal regions where, despite an increasing particle supply, the current remains constant while particles redistribute in the system. Exploiting a domain wall approach with mean-field approximation, we provide a theoretical ground for our findings. The results in steady-state current and density profiles provide quantitative insights into the regulation of the transcription and translation process in bacterial protein synthesis. PMID- 24229137 TI - Effects of adaptive dynamical linking in networked games. AB - The role of dynamical topologies in the evolution of cooperation has received considerable attention, as some studies have demonstrated that dynamical networks are much better than static networks in terms of boosting cooperation. Here we study a dynamical model of evolution of cooperation on stochastic dynamical networks in which there are no permanent partners to each agent. Whenever a new link is created, its duration is randomly assigned without any bias or preference. We allow the agent to adaptively adjust the duration of each link during the evolution in accordance with the feedback from game interactions. By Monte Carlo simulations, we find that cooperation can be remarkably promoted by this adaptive dynamical linking mechanism both for the game of pairwise interactions, such as the Prisoner's Dilemma game (PDG), and for the game of group interactions, illustrated by the public goods game (PGG). And the faster the adjusting rate, the more successful the evolution of cooperation. We also show that in this context weak selection favors cooperation much more than strong selection does. What is particularly meaningful is that the prosperity of cooperation in this study indicates that the rationality and selfishness of a single agent in adjusting social ties can lead to the progress of altruism of the whole population. PMID- 24229138 TI - Scaling in the aging dynamics of the site-diluted Ising model. AB - We study numerically the phase-ordering kinetics of the two-dimensional site diluted Ising model. The data can be interpreted in a framework motivated by renormalization-group concepts. Apart from the usual fixed point of the nondiluted system, there exist two disorder fixed points, characterized by logarithmic and power-law growth of the ordered domains. This structure gives rise to a rich scaling behavior, with an interesting crossover due to the competition between fixed points, and violation of superuniversality. PMID- 24229139 TI - Fluids in porous media: the case of neutral walls. AB - The bulk phase behavior of a fluid is typically altered when the fluid is brought into confinement by the walls of a random porous medium. Inside the porous medium, phase-transition points are shifted, or may disappear altogether. A crucial determinant is how the walls interact with the fluid particles. In this work, we consider the situation whereby the walls are neutral with respect to the liquid and vapor phases. In order to realize the condition of strict neutrality, we use a symmetric binary mixture inside a porous medium that interacts identically with mixture species. Monte Carlo simulations are then used to obtain the phase behavior. Our main finding is that, in the presence of the porous medium, a liquid-vapor critical point still exists. At the critical point, the distribution of the order parameter remains scale invariant, but self-averaging is violated. These findings provide further evidence that random confinement by neutral walls induces critical behavior of the random Ising model (i.e., Ising models with dilution type disorder, where the disorder couples to the energy). PMID- 24229140 TI - Theory of warm ionized gases: equation of state and kinetic Schottky anomaly. AB - Based on accurate Lennard-Jones-type interaction potentials, we derive a closed set of state equations for the description of warm atomic gases in the presence of ionization processes. The specific heat is predicted to exhibit peaks in correspondence to single and multiple ionizations. Such kinetic analog in atomic gases of the Schottky anomaly in solids is enhanced at intermediate and low atomic densities. The case of adiabatic compression of noble gases is analyzed in detail and the implications on sonoluminescence are discussed. In particular, the predicted plasma electron density in a sonoluminescent bubble turns out to be in good agreement with the value measured in recent experiments. PMID- 24229141 TI - Driven flow with exclusion and transport in graphenelike structures. AB - We study driven flow with exclusion in graphenelike structures. The totally asymmetric simple exclusion process (TASEP), a well-known model in its strictly one-dimensional (chain) version, is generalized to cylinder (nanotube) and ribbon (nanoribbon) geometries. A mean-field theoretical description is given for very narrow ribbons ("necklaces") and nanotubes. For specific configurations of bond transmissivity rates, and for a variety of boundary conditions, theory predicts equivalent steady-state behavior between (sublattices on) these structures and chains. This is verified by numerical simulations, to excellent accuracy, by evaluating steady-state currents. We also numerically treat ribbons of general width. We examine the adequacy of this model to the description of electronic transport in carbon nanotubes and nanoribbons or specifically designed quantum dot arrays. PMID- 24229142 TI - Nonequilibrium thermodynamics of the soft glassy rheology model. AB - The soft glassy rheology (SGR) model is a mesoscopic framework which proved to be very successful in describing flow and deformation of various amorphous materials phenomenologically (e.g., pastes, slurries, foams, etc.). In this paper, we cast SGR in a general, model-independent framework for nonequilibrium thermodynamics called general equation for the nonequilibrium reversible-irreversible coupling. This leads to a formulation of SGR which clarifies how it can properly be coupled to hydrodynamic fields, resulting in a thermodynamically consistent, local, continuum version of SGR. Additionally, we find that compliance with thermodynamics imposes the existence of a modification to the stress tensor as predicted by SGR. PMID- 24229143 TI - Local thermodynamics and the generalized Gibbs-Duhem equation in systems with long-range interactions. AB - The local thermodynamics of a system with long-range interactions in d dimensions is studied using the mean-field approximation. Long-range interactions are introduced through pair interaction potentials that decay as a power law in the interparticle distance. We compute the local entropy, Helmholtz free energy, and grand potential per particle in the microcanonical, canonical, and grand canonical ensembles, respectively. From the local entropy per particle we obtain the local equation of state of the system by using the condition of local thermodynamic equilibrium. This local equation of state has the form of the ideal gas equation of state, but with the density depending on the potential characterizing long-range interactions. By volume integration of the relation between the different thermodynamic potentials at the local level, we find the corresponding equation satisfied by the potentials at the global level. It is shown that the potential energy enters as a thermodynamic variable that modifies the global thermodynamic potentials. As a result, we find a generalized Gibbs Duhem equation that relates the potential energy to the temperature, pressure, and chemical potential. For the marginal case where the power of the decaying interaction potential is equal to the dimension of the space, the usual Gibbs Duhem equation is recovered. As examples of the application of this equation, we consider spatially uniform interaction potentials and the self-gravitating gas. We also point out a close relationship with the thermodynamics of small systems. PMID- 24229144 TI - Microcanonical work and fluctuation relations for an open system: An exactly solvable model. AB - We calculate the probability distribution of work for an exactly solvable model of a system interacting with its environment. The system of interest is a harmonic oscillator with a time-dependent control parameter, the environment is modeled by N-independent harmonic oscillators with arbitrary frequencies, and the system-environment coupling is bilinear and not necessarily weak. The initial conditions of the combined system and environment are sampled from a microcanonical distribution and the system is driven out of equilibrium by changing the control parameter according to a prescribed protocol. In the limit of infinitely large environment, i.e., N->infinity, we recover the nonequilibrium work relation and Crooks's fluctuation relation. Moreover, the microcanonical Crooks relation is verified for finite environments. Finally, we show the equivalence of multitime correlation functions of the system in the infinite environment limit for canonical and microcanonical ensembles. PMID- 24229145 TI - Emergence of fractals in aggregation with stochastic self-replication. AB - We propose and investigate a simple model which describes the kinetics of aggregation of Brownian particles with stochastic self-replication. An exact solution and the scaling theory are presented alongside numerical simulation which fully support all theoretical findings. In particular, we show analytically that the particle size distribution function exhibits dynamic scaling and we verify it numerically using the idea of data collapse. Furthermore, the conditions under which the resulting system emerges as a fractal are found, the fractal dimension of the system is given, and the relationship between this fractal dimension and a conserved quantity is pointed out. PMID- 24229146 TI - Effect of coordination number on the nonequilibrium critical point. AB - We study the nonequilibrium critical point of the zero-temperature random-field Ising model on a triangular lattice and compare it with known results on honeycomb, square, and simple cubic lattices. We suggest that the coordination number of the lattice rather than its dimension plays the key role in determining the universality class of the nonequilibrium critical behavior. This is discussed in the context of numerical evidence that equilibrium and nonequilibrium critical points of the zero-temperature random-field Ising model belong to the same universality class. The physics of this curious result is not fully understood. PMID- 24229147 TI - Isomorphs, hidden scale invariance, and quasiuniversality. AB - This paper first establishes an approximate scaling property of the potential energy function of a classical liquid with good isomorphs (a Roskilde-simple liquid). This "pseudohomogeneous" property makes explicit that-and in which sense such a system has a hidden scale invariance. The second part of the paper gives a potential-energy formulation of the quasiuniversality of monatomic Roskilde simple liquids, which was recently rationalized in terms of the existence of a quasiuniversal single-parameter family of reduced-coordinate constant-potential energy hypersurfaces [J. C. Dyre, Phys. Rev. E 87, 022106 (2013)]. The new formulation involves a quasiuniversal reduced-coordinate potential-energy function. A few consequences of this are discussed. PMID- 24229148 TI - Depletion-interaction effects on the tunneling conductivity of nanorod suspensions. AB - We study by simulation and theory how the addition of insulating spherical particles affects the conductivity of fluids of conducting rods, modeled by spherocylinders. The electrical connections are implemented as tunneling processes, leading to a more detailed and realistic description than a discontinuous percolation approach. We find that the spheres enhance the tunneling conductivity for a given concentration of rods and that the enhancement increases with rod concentration into the regime where the conducting network is well established. By reformulating the network of rods using a critical path analysis, we quantify the effect of depletion-induced attraction between the rods due to the spheres. Furthermore, we show that our conductivity data are quantitatively reproduced by an effective-medium approximation, which explicitly relates the system tunneling conductance to the structure of the rod-sphere fluid. PMID- 24229149 TI - Multicritical behavior in models with two competing order parameters. AB - We employ the nonperturbative functional renormalization group to study models with an O(N(1) ?O(N)(2)) symmetry. Here different fixed points exist in three dimensions, corresponding to bicritical and tetracritical behavior induced by the competition of two order parameters. We discuss the critical behavior of the symmetry-enhanced isotropic, the decoupled and the biconical fixed point, and analyze their stability in the N(1),N(2) plane. We study the fate of nontrivial fixed points during the transition from three to four dimensions, finding evidence for a triviality problem for coupled two-scalar models in high-energy physics. We also point out the possibility of noncanonical critical exponents at semi-Gaussian fixed points and show the emergence of Goldstone modes from discrete symmetries. PMID- 24229150 TI - Memory effects for a trapped Brownian particle in viscoelastic shear flows. AB - The long-time limit behavior of the positional distribution for an underdamped Brownian particle in a fluctuating harmonic potential well, which is simultaneously exposed to an oscillatory viscoelastic shear flow is investigated using the generalized Langevin equation with a power-law-type memory kernel. The influence of a fluctuating environment is modeled by a multiplicative white noise (fluctuations of the stiffness of the trapping potential) and by an additive internal fractional Gaussian noise. The exact expressions of the second-order moments of the fluctuating position for the Brownian particle in the shear plane have been calculated. Also, shear-induced cross correlation between particle fluctuations along orthogonal directions as well as the angular momentum are found. It is shown that interplay of shear flow, memory, and multiplicative noise can generate a variety of cooperation effects, such as energetic instability, multiresonance versus the shear frequency, and memory-induced anomalous diffusion in the direction of the shear flow. Particularly, two different critical memory exponents have been found, which mark dynamical transitions from a stationary regime to a subdiffusive (or superdiffusive) regime of the system. Similarities and differences between the behaviors of the models with oscillatory and nonoscillatory shear flow are also discussed. PMID- 24229151 TI - Second law of information thermodynamics with entanglement transfer. AB - We present an inequality which holds in the thermodynamical processes with measurement and feedback controls and uses only the Helmholtz free energy and the entanglement of formation: W(ext)<=-DeltaF-k(B)TDeltaE(F). The quantity DeltaE(F), which is positive, expresses the amount of entanglement transfer from system S to probe P through the interaction U(SP) during the measurement. It is easier to achieve the upper bound in this inequality than in the Sagawa-Ueda inequality [Phys. Rev. Lett. 100, 080403 (2008)]. Our inequality has clear physical meaning: in the above thermodynamical processes, the work which we can extract from the thermodynamic system is greater than the upper bound in the conventional thermodynamics by the amount of the entanglement extracted by the measurement. PMID- 24229152 TI - Principle of maximum Fisher information from Hardy's axioms applied to statistical systems. AB - Consider a finite-sized, multidimensional system in parameter state a. The system is either at statistical equilibrium or general nonequilibrium, and may obey either classical or quantum physics. L. Hardy's mathematical axioms provide a basis for the physics obeyed by any such system. One axiom is that the number N of distinguishable states a in the system obeys N=max. This assumes that N is known as deterministic prior knowledge. However, most observed systems suffer statistical fluctuations, for which N is therefore only known approximately. Then what happens if the scope of the axiom N=max is extended to include such observed systems? It is found that the state a of the system must obey a principle of maximum Fisher information, I=I(max). This is important because many physical laws have been derived, assuming as a working hypothesis that I=I(max). These derivations include uses of the principle of extreme physical information (EPI). Examples of such derivations were of the De Broglie wave hypothesis, quantum wave equations, Maxwell's equations, new laws of biology (e.g., of Coulomb force directed cell development and of in situ cancer growth), and new laws of economic fluctuation and investment. That the principle I=I(max) itself derives from suitably extended Hardy axioms thereby eliminates its need to be assumed in these derivations. Thus, uses of I=I(max) and EPI express physics at its most fundamental level, its axiomatic basis in math. PMID- 24229153 TI - Insight into the so-called spatial reciprocity. AB - Up to now, there have been a great number of studies that demonstrate the effect of spatial topology on the promotion of cooperation dynamics (namely, the so called "spatial reciprocity"). However, most researchers probably attribute it to the positive assortment of strategies supported by spatial arrangement. In this paper, we analyze the time course of cooperation evolution under different evolution rules. Interestingly, a typical evolution process can be divided into two evident periods: the enduring (END) period and the expanding (EXP) period where the former features that cooperators try to endure defectors' invasion and the latter shows that perfect C clusters fast expand their area. We find that the final cooperation level relies on two key factors: the formation of the perfect C cluster at the end of the END period and the expanding fashion of the perfect C cluster during the EXP period. For deterministic rule, the smooth expansion of C cluster boundaries enables cooperators to reach a dominant state, whereas, the rough boundaries for stochastic rule cannot provide a sufficient beneficial environment for the evolution of cooperation. Moreover, we show that expansion of the perfect C cluster is closely related to the cluster coefficient of interaction topology. To some extent, we present a viable method for understanding the spatial reciprocity mechanism in nature and hope that it will inspire further studies to resolve social dilemmas. PMID- 24229154 TI - Uncovering wind turbine properties through two-dimensional stochastic modeling of wind dynamics. AB - Using a method for stochastic data analysis borrowed from statistical physics, we analyze synthetic data from a Markov chain model that reproduces measurements of wind speed and power production in a wind park in Portugal. We show that our analysis retrieves indeed the power performance curve, which yields the relationship between wind speed and power production, and we discuss how this procedure can be extended for extracting unknown functional relationships between pairs of physical variables in general. We also show how specific features, such as the rated speed of the wind turbine or the descriptive wind speed statistics, can be related to the equations describing the evolution of power production and wind speed at single wind turbines. PMID- 24229155 TI - Duality of diffusion dynamics in particle motion in soft-mode turbulence. AB - Nonthermal Brownian motion is investigated experimentally by injecting a particle into soft-mode turbulence (SMT), in the electroconvection of a nematic liquid crystal. It is clarified that the particle motion can be classified into two phases: fast motion, where particles move with the local convective flow, and slow motion, where they are carried by global slow pattern dynamics. We propose a simplified model to clarify the mechanism of the short-time and asymptotic behavior of diffusion. In our model, the correlation time is estimated as a function of a control parameter E. The scaling of the SMT pattern correlation time, tau(d)~E(-1), is estimated from the particle dynamics, which is consistent with a previous report observed from the Eulerian viewpoint. The origin of the non-Gaussian distribution of the displacement in the short-time regime is also discussed and an analytical curve is introduced that quantitatively agrees with the experimental data. Our results clearly illustrate the characteristics of diffusive motion in SMT, which are considerably different from the conventional Brownian motion. PMID- 24229156 TI - Irreversible bimolecular chemical reactions on directed scale-free networks. AB - Kinetics of irreversible bimolecular chemical reactions A+A->0 and A+B->0 on directed scale-free networks with the in-degree distribution P(in)(k)~k( gamma)(in) and the out-degree distribution P(out)(l)~l(-gamma)(out) are investigated. Since the correlation between k and l of each node generally exists in directed networks, we control the correlation (kl) with the probability r?[0,1] by two different algorithms for the construction of the directed networks, i.e., the so-called k and l algorithms. For r=1, the k algorithm gives (kl)=(k(2)), whereas the l algorithm gives (kl)=(l(2). For r=0, (kl)=(k)(l) for both algorithms. The kinetics of both reactions are analyzed using heterogeneous mean-field (HMF) theory and Monte Carlo simulations. The density of particles (rho) algebraically decays in time t as rho(t)~t(-alpha). The kinetics of both reactions are determined by the same rate equation, drho/dt=arho(2)+brho(theta 1), apart from coefficients. The exponent theta is determined by the algorithm: theta=gamma(in) for the k algorithm (r>=0) and theta=gamma(min) for the l algorithm (r>0), where gamma(min) is the smaller exponent between gamma(in) and gamma(out). For theta>3, one observes the ordinary mean-field kinetics, rho~1/t (alpha=1). In contrast, for theta<3, rho(t) anomalously decays with alpha=1/(theta-2). The HMF predictions are confirmed by the simulations on quenched directed networks. PMID- 24229157 TI - Molecules with an induced dipole moment in a stochastic electric field. AB - The mean-field dynamics of a molecule with an induced dipole moment (e.g., a homonuclear diatomic molecule) in a deterministic and a stochastic (fluctuating) electric field is solved to obtain the decoherence properties of the system. The average (over fluctuations) electric dipole moment and average angular momentum as a function of time for a Gaussian white noise electric field are determined via perturbative and nonperturbative solutions in the fluctuating field. In the perturbative solution, the components of the average electric dipole moment and the average angular momentum along the deterministic electric field direction do not decay to zero, despite fluctuations in all three components of the electric field. This is in contrast to the decay of the average over fluctuations of a magnetic moment in a Gaussian white noise magnetic field. In the nonperturbative solution, the component of the average electric dipole moment and the average angular momentum in the deterministic electric field direction also decay to zero. PMID- 24229158 TI - Equivalence between fractional exclusion statistics and self-consistent mean field theory in interacting-particle systems in any number of dimensions. AB - We describe a mean field interacting particle system in any number of dimensions and in a generic external potential as an ideal gas with fractional exclusion statistics (FES). We define the FES quasiparticle energies, we calculate the FES parameters of the system and we deduce the equations for the equilibrium particle populations. The FES gas is "ideal," in the sense that the quasiparticle energies do not depend on the other quasiparticle levels' populations and the sum of the quasiparticle energies is equal to the total energy of the system. We prove that the FES formalism is equivalent to the semiclassical or Thomas Fermi limit of the self-consistent mean-field theory and the FES quasiparticle populations may be calculated from the Landau quasiparticle populations by making the correspondence between the FES and the Landau quasiparticle energies. The FES provides a natural semiclassical ideal gas description of the interacting particle gas. PMID- 24229159 TI - Coarse graining for the phase-field model of fast phase transitions. AB - Fast phase transitions under lack of local thermalization between successive elementary steps of the physical process are treated analytically. Non-Markovian master equations are derived for fast processes, which do not have enough time to reach energy or momentum thermalization during rapid phase change or freezing of a highly nonequilibrium system. These master equations provide a further physical basis for evolution and transport equations of the phase-field model used previously in the analyses of fast phase transitions. PMID- 24229160 TI - Unstable supercritical discontinuous percolation transitions. AB - The location and nature of the percolation transition in random networks is a subject of intense interest. Recently, a series of graph evolution processes have been introduced that lead to discontinuous percolation transitions where the addition of a single edge causes the size of the largest component to exhibit a significant macroscopic jump in the thermodynamic limit. These processes can have additional exotic behaviors, such as displaying a "Devil's staircase" of discrete jumps in the supercritical regime. Here we investigate whether the location of the largest jump coincides with the percolation threshold for a range of processes, such as Erdos-Renyipercolation, percolation via edge competition and via growth by overtaking. We find that the largest jump asymptotically occurs at the percolation transition for Erdos-Renyiand other processes exhibiting global continuity, including models exhibiting an "explosive" transition. However, for percolation processes exhibiting genuine discontinuities, the behavior is substantially richer. In percolation models where the order parameter exhibits a staircase, the largest discontinuity generically does not coincide with the percolation transition. For the generalized Bohman-Frieze-Wormald model, it depends on the model parameter. Distinct parameter regimes well in the supercritical regime feature unstable discontinuous transitions-a novel and unexpected phenomenon in percolation. We thus demonstrate that seemingly and genuinely discontinuous percolation transitions can involve a rich behavior in supercriticality, a regime that has been largely ignored in percolation. PMID- 24229161 TI - Granular transport in a horizontally vibrated sawtooth channel. AB - We present a new mode of transport of spherical particles in a horizontally vibrated channel with sawtooth-shaped side walls. The underlying driving mechanism is based on an interplay of directional energy injection transformed by the sidewall collisions and density-dependent interparticle collisions. Experiments and matching numerics show that the average particle velocity reaches a maximum at 60% of the maximal filling density. Introducing a spatial phase shift between the channel boundaries increases the transport velocity by an order of magnitude. PMID- 24229162 TI - Shape-induced chiral ordering in two-dimensional packing of snowmanlike dimeric particles. AB - Understanding the distinctive phase behaviors in random packing due to particle shapes is an important issue in condensed matter physics. In this paper, we investigate the random packing structure of two-dimensional (2D) snowmen via wax snowman packing experiments and Brownian dynamics simulations. Both experiments and simulations reveal that neighboring snowmen have a strong short-range orientational correlation and consequently locally form particular conformations. A chiral conformation is dominant for high area fractions near the jamming condition (phi>0.8), and the proportion of the chiral conformation increases with gamma. We also found that the attractive interaction does not have a significant impact on the results. The geometry of chirally ordered snowmen causes a mismatch with 2D crystalline symmetries and thus inhibits the development of long-range spatial order, despite the strong orientational correlation between neighbors. PMID- 24229163 TI - Universal features of the jamming phase diagram of wet granular materials. AB - We investigate the influence of the shape of a particle on the structure of the jamming phase diagram of wet granular materials. We compute the jamming phase diagram of wet dimers (two fused disks) and compare it with that of the wet disks. Amplitude of the external force at solidification, i.e., the jamming force F(s), is computed as a function of the packing fraction phi, the capillary bridge energy E, and the aspect ratio of dimers alpha. Based on data collapse, an equation for amplitude of the external force at solidification F(s)(phi,E,alpha) is derived. F(s) has scaling and logarithmic relations with phi and E, respectively, exactly the same type reported for wet disks earlier. Interestingly, F(s) does not depend on the aspect ratio of dimers alpha. The only difference is that wet dimers are found to be more stiffer than wet disks. However, the similarities of the equations describing F(s)(phi,E,alpha) of wet dimers and disks imply that there exists, yet unknown, universal aspects of mechanical response of wet granular materials to the external forces, independent from the particle shape. In addition, we study local orientation of particles and its statistical properties. PMID- 24229164 TI - Sedimentation of granular columns in the viscous and weakly inertial regimes. AB - We investigate the dynamics of granular columns of point particles that interact via long-range hydrodynamic interactions and fall under the action of gravity. We investigate the influence of inertia using the Green's function for the Oseen equation. The initial conditions (density and aspect ratio) are systematically varied. Our results suggest that universal self-similar laws may be sufficient to characterize the temporal and structural evolution of the granular columns. A characteristic time above which an instability is triggered (which may enable the formation of clusters) is also retrieved and discussed. PMID- 24229166 TI - Dynamic equivalences in the hard-sphere dynamic universality class. AB - We perform systematic simulation experiments on model systems with soft-sphere repulsive interactions to test the predicted dynamic equivalence between soft sphere liquids with similar static structure. For this we compare the simulated dynamics (mean squared displacement, intermediate scattering function, alpha relaxation time, etc.) of different soft-sphere systems, between them and with the hard-sphere liquid. We then show that the referred dynamic equivalence does not depend on the (Newtonian or Brownian) nature of the microscopic laws of motion of the constituent particles, and hence, applies independently to colloidal and to atomic simple liquids. Finally, we verify another more recently proposed dynamic equivalence, this time between the long-time dynamics of an atomic liquid and its corresponding Brownian fluid (i.e., the Brownian system with the same interaction potential). PMID- 24229165 TI - Small-amplitude acoustics in bulk granular media. AB - We propose and validate a three-dimensional continuum modeling approach that predicts small-amplitude acoustic behavior of dense-packed granular media. The model is obtained through a joint experimental and finite-element study focused on the benchmark example of a vibrated container of grains. Using a three parameter linear viscoelastic constitutive relation, our continuum model is shown to quantitatively predict the effective mass spectra in this geometry, even as geometric parameters for the environment are varied. Further, the model's predictions for the surface displacement field are validated mode-by-mode against experiment. A primary observation is the importance of the boundary condition between grains and the quasirigid walls. PMID- 24229167 TI - Applicability of mode-coupling theory to polyisobutylene: a molecular dynamics simulation study. AB - The applicability of Mode Coupling Theory (MCT) to the glass-forming polymer polyisobutylene (PIB) has been explored by using fully atomistic molecular dynamics simulations. MCT predictions for the so-called asymptotic regime have been successfully tested on the dynamic structure factor and the self-correlation function of PIB main-chain carbons calculated from the simulated cell. The factorization theorem and the time-temperature superposition principle are satisfied. A consistent fitting procedure of the simulation data to the MCT asymptotic power-laws predicted for the alpha-relaxation regime has delivered the dynamic exponents of the theory-in particular, the exponent parameter lambda-the critical non-ergodicity parameters, and the critical temperature T(c). The obtained values of lambda and T(c) agree, within the uncertainties involved in both studies, with those deduced from depolarized light scattering experiments [A. Kisliuk et al., J. Polym. Sci. Part B: Polym. Phys. 38, 2785 (2000)]. Both, lambda and T(c)/T(g) values found for PIB are unusually large with respect to those commonly obtained in low molecular weight systems. Moreover, the high T(c)/T(g) value is compatible with a certain correlation of this parameter with the fragility in Angell's classification. Conversely, the value of lambda is close to that reported for real polymers, simulated "realistic" polymers and simple polymer models with intramolecular barriers. In the framework of the MCT, such finding should be the signature of two different mechanisms for the glass transition in real polymers: intermolecular packing and intramolecular barriers combined with chain connectivity. PMID- 24229168 TI - Normal-stress coefficients and rod climbing in colloidal dispersions. AB - We calculate tractable microscopic expressions for the low-shear normal-stress coefficients of colloidal dispersions. Although restricted to the low rate regime, the presented formulas are valid for all volume fractions below the glass transition and for any interaction potential. Numerical results are presented for a system of colloids interacting via a hard-core attractive Yukawa potential, for which we explore the interplay between attraction strength and volume fraction. We show that the normal-stress coefficients exhibit nontrivial features close to the critical point and at high volume fractions in the vicinity of the reentrant glass transition. Finally, we exploit our formulas to make predictions about rod climbing effects in attractive colloidal dispersions. PMID- 24229169 TI - Dynamical correlations in a glass former with randomly pinned particles. AB - The effects of randomly pinning particles in a model glass-forming fluid are studied, with a focus on the dynamically heterogeneous relaxation in the presence of pinning. We show how four-point dynamical correlations can be analyzed in real space, allowing direct extraction of a length scale that characterizes dynamical heterogeneity. In the presence of pinning, the relaxation time of the glassy system increases by up to two decades, but there is almost no increase in either the four-point correlation length or the strength of the four-point correlations. We discuss the implications of these results for theories of the glass transition. PMID- 24229170 TI - Stripe, gossamer, and glassy phases in systems with strong nonpairwise interactions. AB - We study structure formation in systems of classical particles in two dimensions with long-range attractive short-range repulsive two-body interactions and repulsive three-body interactions. Stripe, gossamer, and glass phases are found as a result of nonpairwise interaction. PMID- 24229171 TI - Dynamics and separation of circularly moving particles in asymmetrically patterned arrays. AB - There are many examples of driven and active matter systems containing particles that exhibit circular motion with different chiralities, such as swimming bacteria near surfaces or certain types of self-driven colloidal particles. Circular motion of passive particles can also be induced with an external rotating drive. Here we examine particles that move in circles and interact with a periodic array of asymmetric L-shaped obstacles. We find a series of dynamical phases as a function of swimming radius, including regimes where the particle motion is rectified, producing a net dc motion. The direction of the rectification varies with the swimming radius, permitting the separation of particles with different swimming radii. Particles with the same swimming radius but different chirality can also move in different directions over the substrate and be separated. The rectification occurs for specific windows of swimming radii corresponding to periodic orbits in which the particles interact one or more times with the barriers per rotation cycle. The rectification effects are robust against the addition of thermal or diffusive effects, and are in some cases even enhanced by these effects. PMID- 24229172 TI - Characteristics of the Johari-Goldstein process in rigid asymmetric molecules. AB - Molecular dynamics simulations were carried out on a Lennard-Jones binary mixture of rigid (fixed bond length) diatomic molecules. The translational and rotational correlation functions, and the corresponding susceptibilities, exhibit two relaxation processes: the slow structural relaxation (alpha dynamics) and a higher frequency secondary relaxation. The latter is a Johari-Goldstein (JG) process, by its definition of involving all parts of the molecule. It shows several properties characteristic of the JG relaxation: (1) merging with the alpha relaxation at high temperature; (2) a change in temperature dependence of its relaxation strength on vitrification; (3) a separation in frequency from the alpha peak that correlates with the breadth of the alpha dispersion; and (4) sensitivity to volume, pressure, and physical aging. These properties can be used to determine whether a secondary relaxation in a real material is an authentic JG process, rather than more trivial motion involving intramolecular degrees of freedom. The latter has no connection to the glass transition, whereas the JG relaxation is closely related to structural relaxation, and thus can provide new insights into the phenomenon. PMID- 24229173 TI - Manifestation of random first-order transition theory in Wigner glasses. AB - We use Brownian dynamics simulations of a binary mixture of highly charged spherical colloidal particles to test some of the predictions of the random first order transition (RFOT) theory [Phys. Rev. Lett. 58, 2091 (1987); Phys. Rev. A 40, 1045 (1989)]. In accord with mode-coupling theory and RFOT, we find that as the volume fraction of the colloidal particles phi approaches the dynamical transition value phi(A), three measures of dynamics show an effective ergodic to nonergodic transition. First, there is a dramatic slowing down of diffusion, with the translational diffusion constant decaying as a power law as phi->phi(A)(-). Second, the energy metric, a measure of ergodicity breaking in classical many body systems, shows that the system becomes effectively nonergodic as phi(A) is approached. Finally, the time t(*), at which the four-point dynamical susceptibility achieves a maximum, also increases as a power law near phi(A). Remarkably, the translational diffusion coefficients, ergodic diffusion coefficient, and (t(*))(-) all vanish as (phi(-1)-phi(A)(-1))(gamma) with both phi(A)(~0.1) and gamma being the roughly the same for all three quantities. Above phi(A), transport involves crossing free energy barriers. In this regime, the density-density correlation function decays as a stretched exponential [exp (t/tau(alpha))(beta)] with beta~0.45. The phi dependence of the relaxation time tau(alpha) could be fit using the Vogel-Tamman-Fulcher law with the ideal glass transition at phi(K)~0.47. By using a local entropy measure, we show that the law of large numbers is not obeyed above phi(A), and gives rise to subsample to subsample fluctuations in all physical observables. We propose that dynamical heterogeneity is a consequence of violation of law of large numbers. PMID- 24229174 TI - Probing the limitations of isotropic pair potentials to produce ground-state structural extremes via inverse statistical mechanics. AB - Inverse statistical-mechanical methods have recently been employed to design optimized short-range radial (isotropic) pair potentials that robustly produce novel targeted classical ground-state many-particle configurations. The target structures considered in those studies were low-coordinated crystals with a high degree of symmetry. In this paper, we further test the fundamental limitations of radial pair potentials by targeting crystal structures with appreciably less symmetry, including those in which the particles have different local structural environments. These challenging target configurations demanded that we modify previous inverse optimization techniques. In particular, we first find local minima of a candidate enthalpy surface and determine the enthalpy difference DeltaH between such inherent structures and the target structure. Then we determine the lowest positive eigenvalue lambda(0) of the Hessian matrix of the enthalpy surface at the target configuration. Finally, we maximize lambda(0)DeltaH so that the target structure is both locally stable and globally stable with respect to the inherent structures. Using this modified optimization technique, we have designed short-range radial pair potentials that stabilize the two-dimensional kagome crystal, the rectangular kagome crystal, and rectangular lattices, as well as the three-dimensional structure of the CaF(2) crystal inhabited by a single-particle species. We verify our results by cooling liquid configurations to absolute zero temperature via simulated annealing and ensuring that such states have stable phonon spectra. Except for the rectangular kagome structure, all of the target structures can be stabilized with monotonic repulsive potentials. Our work demonstrates that single-component systems with short-range radial pair potentials can counterintuitively self-assemble into crystal ground states with low symmetry and different local structural environments. Finally, we present general principles that offer guidance in determining whether certain target structures can be achieved as ground states by radial pair potentials. PMID- 24229175 TI - Thermodynamics of ferrofluids in applied magnetic fields. AB - The thermodynamic properties of ferrofluids in applied magnetic fields are examined using theory and computer simulation. The dipolar hard sphere model is used. The second and third virial coefficients (B(2) and B(3)) are evaluated as functions of the dipolar coupling constant lambda, and the Langevin parameter alpha. The formula for B(3) for a system in an applied field is different from that in the zero-field case, and a derivation is presented. The formulas are compared to results from Mayer-sampling calculations, and the trends with increasing lambda and alpha are examined. Very good agreement between theory and computation is demonstrated for the realistic values lambda<=2. The analytical formulas for the virial coefficients are incorporated in to various forms of virial expansion, designed to minimize the effects of truncation. The theoretical results for the equation of state are compared against results from Monte Carlo simulations. In all cases, the so-called logarithmic free energy theory is seen to be superior. In this theory, the virial expansion of the Helmholtz free energy is re-summed in to a logarithmic function. Its success is due to the approximate representation of high-order terms in the virial expansion, while retaining the exact low-concentration behavior. The theory also yields the magnetization, and a comparison with simulation results and a competing modified mean-field theory shows excellent agreement. Finally, the putative field-dependent critical parameters for the condensation transition are obtained and compared against existing simulation results for the Stockmayer fluid. Dipolar hard spheres do not undergo the transition, but the presence of isotropic attractions, as in the Stockmayer fluid, gives rise to condensation even in zero field. A comparison of the relative changes in critical parameters with increasing field strength shows excellent agreement between theory and simulation, showing that the theoretical treatment of the dipolar interactions is robust. PMID- 24229176 TI - Fluctuations in the time variable and dynamical heterogeneity in glass-forming systems. AB - We test a hypothesis for the origin of dynamical heterogeneity in slowly relaxing systems, namely that it emerges from soft (Goldstone) modes associated with a broken continuous symmetry under time reparametrizations. We do this by constructing coarse grained observables and decomposing the fluctuations of these observables into transverse components, which are associated with the postulated time-fluctuation soft modes, and a longitudinal component, which represents the rest of the fluctuations. Our test is performed on data obtained in simulations of four models of structural glasses. As the hypothesis predicts, we find that the time reparametrization fluctuations become increasingly dominant as temperature is lowered and timescales are increased. More specifically, the ratio between the strengths of the transverse fluctuations and the longitudinal fluctuations grows as a function of the dynamical susceptibility, chi(4), which represents the strength of the dynamical heterogeneity; and the correlation volumes for the transverse fluctuations are approximately proportional to those for the dynamical heterogeneity, while the correlation volumes for the longitudinal fluctuations remain small and approximately constant. PMID- 24229177 TI - Localized measurement of longitudinal and transverse flow velocities in colloidal suspensions using optical coherence tomography. AB - We report on localized measurement of the longitudinal and transverse flow velocities in a colloidal suspension using optical coherence tomography. We present a model for the path-length resolved autocorrelation function including diffusion and flow, which we experimentally verify. For flow that is not perpendicular to the incident beam, the longitudinal velocity gradient over the coherence gate causes additional decorrelation, which is described by our model. We demonstrate simultaneous imaging of sample morphology and longitudinal and transverse flow at micrometer scale in a single measurement. PMID- 24229178 TI - Structural ordering of trapped colloids with competing interactions. AB - The structure of colloids with competing interactions which are confined in a harmonic external trap potential is analyzed numerically by energy minimization in two spatial dimensions. A wealth of different cluster structures is found to be stable including clusters with a fringed outer rim (reminiscent to an ornamental border), clusters perforated with voids, as well as clusters with a crystalline core and a disordered rim. All cluster structures occur in a two dimensional parameter space. The structural ordering can therefore be efficiently tuned by changing few parameters only providing access to a controlled fabrication of colloidal clusters. PMID- 24229179 TI - Scattering approach for fluctuation-induced interactions at fluid interfaces. AB - We develop the scattering formalism to calculate the interaction between colloidal particles trapped at a fluid interface. Since, in addition to the interface, the colloids may also fluctuate in this system, we implement the fluctuation of the boundaries into the scattering formalism and investigate how the interaction between colloids is modified by their fluctuations. This general method can be applied to any number of colloids with various geometries at an interface. We apply the formalism derived in this work to a system of spherical colloids at the interface between two fluid phases. For two spherical colloids, this method very effectively reproduces the previous known results. For three particles we find analytical expressions for the large separation asymptotic energies and numerically calculate the Casimir interaction at all separations. Our results show an interesting three-body effect for fixed and fluctuating colloids. While the three-body effect strengthens the attractive interaction between fluctuating colloids, it diminishes the attractive force between colloids fixed at an interface. PMID- 24229180 TI - Slow relaxation in structure-forming ferrofluids. AB - We study the behavior of colloidal magnetic fluids at low density for various dipolar interaction strengths by performing extensive Langevin dynamics simulations with model parameters that mimic cobalt-based ferrofluids used in experiments. Our study mainly focuses on the structural and dynamical properties of dipolar fluids and the influence of structural changes on their dynamics. Drastic changes from chainlike to networklike structures in the absence of an external magnetic field are observed. This crossover plays an important role in the slowing down of dynamics that is reflected in various dynamical properties including the tracer diffusion and the viscosity and also in the structural relaxation. PMID- 24229181 TI - Broadband ultrasonic spectrometry of polystyrene-cyclohexane critical mixtures. AB - Mutual diffusion coefficients, shear viscosities, and broadband ultrasonic attenuation spectra in the frequency range 100 kHz to 300 MHz have been measured for solutions of polystyrene in cyclohexane at two degrees of polymerization N and various temperatures near the critical. The exponent y(eta) in the power law representation of the critical part in the viscosity deviates substantially from the universal value y(eta) = 0.0435: y(eta) = 0.028 (N = 288) and y(eta) = 0.014 (N = 6242). Also, the adiabatic coupling constant g and the amplitudes xi(0) and Gamma(0) in the power laws of the correlation length and the relaxation rate of fluctuations, respectively, depend on N. This is especially obvious with the relaxation rates, for which Gamma(0) = 5.8*10(9) at N = 288 and Gamma(0) = 6.1*10(7) with the larger polymer results. A noteworthy feature is the difference between the relaxation rates from the diffusion coefficients and shear viscosities on the one hand and from the ultrasonic spectra on the other. Near the critical temperatures the latter Gamma values deviate from power law behavior, indicating a coupling between the concentration fluctuations and structural isomerizations of the polymers. PMID- 24229182 TI - Formation of double glass in binary mixtures of anisotropic particles: dynamic heterogeneities in rotations and displacements. AB - We study glass behavior in a mixture of elliptic and circular particles in two dimensions at low temperatures using an orientation-dependent Lennard-Jones potential. The ellipses have a mild aspect ratio (~1.2) and tend to align at low temperatures, while the circular particles play the role of impurities disturbing the ellipse orientations at a concentration of 20%. These impurities have a size smaller than that of the ellipses and attract them in the homeotropic alignment. As a result, the coordination number around each impurity is mostly 5 or 4 in glassy states. We realize double glass, where both the orientations and the positions are disordered but still hold mesoscopic order. We find a strong heterogeneity in the flip motions of the ellipses, which sensitively depends on the impurity clustering. In our model, a small fraction of the ellipses still undergo flip motions relatively rapidly even at low temperatures. In contrast, the nonflip rotations (with angle changes not close to +/-pi) are mainly caused by the cooperative configuration changes involving many particles. Then, there arises a long-time heterogeneity in the nonflip rotations closely correlated with the dynamic heterogeneity in displacements. PMID- 24229183 TI - Spontaneous formation of hierarchical wrinkles in Cr films deposited on silicone oil drops with constrained edges. AB - We report on the spontaneous formation of hierarchical wrinkling patterns in Cr films deposited on silicone oil drops with constrained edges. The appearance of the wrinkling patterns is strongly dependent on the film thickness and the size of the silicone oil drop. Because the Cr film at the drop edge is constrained due to the strong adhesion between the film and the glass surface, the wrinkle wavelength merely depends on the distance starting from the drop edge. When the distance increases, the wavelength increases quickly first, and then it slows down gradually in compliance with a simple power law. The evolution of the wrinkle amplitude is similar to that of the wavelength, but it is also closely related to the film thickness and the oil drop size. Based on the fact that the silicone oil is polymerized to form an elastic layer during deposition, the formation and evolution of the hierarchical wrinkling patterns have been analyzed in detail. PMID- 24229184 TI - Role of superposition of dislocation avalanches in the statistics of acoustic emission during plastic deformation. AB - Various dynamical systems with many degrees of freedom display avalanche dynamics, which is characterized by scale invariance reflected in power-law statistics. The superposition of avalanche processes in real systems driven at a finite velocity may influence the experimental determination of the underlying power law. The present paper reports results of an investigation of this effect using the example of acoustic emission (AE) accompanying plastic deformation of crystals. Indeed, recent studies of AE did not only prove that the dynamics of crystal defects obeys power-law statistics, but also led to a hypothesis of universality of the scaling law. We examine the sensitivity of the apparent statistics of AE to the parameters applied to individualize AE events. Two different alloys, MgZr and AlMg, both displaying strong AE but characterized by different plasticity mechanisms, are investigated. It is shown that the power-law indices display a good robustness in wide ranges of parameters even in the conditions leading to very strong superposition of AE events, although some deviations from the persistent values are also detected. The totality of the results confirms the scale-invariant character of deformation processes on the scale relevant to AE, but uncovers essential differences between the power-law exponents found for two kinds of alloys. PMID- 24229185 TI - Creasing-wrinkling transition in elastomer films under electric fields. AB - Creasing and wrinkling are different types of instabilities on material surfaces characterized by localized singular folds and continuously smooth undulation, respectively. While it is known that electric fields can induce both types of instabilities in elastomer films bonded on substrates, the relation and transition between the field-induced instabilities have not been analyzed or understood. We show that the surface energy, modulus, and thickness of the elastomer determine the types, critical fields, and wavelengths of the instabilities. By independently varying these parameters of elastomers under electric fields, our experiments demonstrate transitions between creases with short wavelengths and wrinkles with long wavelengths. We further develop a unified theoretical model that accounts for both creasing and wrinkling instabilities induced by electric fields and predicts their transitions. The experimental data agree well with the theoretical model. PMID- 24229186 TI - Strain-rate and temperature-driven transition in the shear transformation zone for two-dimensional amorphous solids. AB - We couple the recently developed self-learning metabasin escape algorithm, which enables efficient exploration of the potential energy surface (PES), with shear deformation to elucidate strain-rate and temperature effects on the shear transformation zone (STZ) characteristics in two-dimensional amorphous solids. In doing so, we report a transition in the STZ characteristics that can be obtained through either increasing the temperature or decreasing the strain rate. The transition separates regions having two distinct STZ characteristics. Specifically, at high temperatures and high strain rates, we show that the STZs have characteristics identical to those that emerge from purely strain-driven, athermal quasistatic atomistic calculations. At lower temperatures and experimentally relevant strain rates, we use the newly coupled PES + shear deformation method to show that the STZs have characteristics identical to those that emerge from a purely thermally activated state. The specific changes in STZ characteristics that occur in moving from the strain-driven to thermally activated STZ regime include a 33% increase in STZ size, faster spatial decay of the displacement field, a change in the deformation mechanism inside the STZ from shear to tension, a reduction in the stress needed to nucleate the first STZ, and finally a notable loss in characteristic quadrupolar symmetry of the surrounding elastic matrix that has previously been seen in athermal, quasistatic shear studies of STZs. PMID- 24229187 TI - Self-organization and nanostructure formation in chemical vapor deposition. AB - When thin films are grown on a substrate by chemical vapor deposition, the evolution of the first deposited layers may be described, on mesoscopic scales, by dynamical models of the reaction-diffusion type. For monatomic layers, such models describe the evolution of atomic coverage due to the combined effect of reaction terms representing adsorption-desorption and chemical processes and nonlinear diffusion terms that are of the Cahn-Hilliard type. This combination may lead, below a critical temperature, to the instability of uniform deposited layers. This instability triggers the formation of nanostructures corresponding to regular spatial variations of substrate coverage. Patterns wavelengths and symmetries are selected by dynamical variables and not by variational arguments. According to the balance between reaction- and diffusion-induced nonlinearities, a succession of nanostructures including hexagonal arrays of dots, stripes, and localized structures of various types may be obtained. These structures may initiate different growth mechanisms, including Volmer-Weber and Frank-Van der Merwe types of growth. The relevance of this approach to the study of deposited layers of different species is discussed. PMID- 24229188 TI - Nonequilibrium kinetic boundary condition at the vapor-liquid interface of argon. AB - A boundary condition for the Boltzmann equation (kinetic boundary condition, KBC) at the vapor-liquid interface of argon is constructed with the help of molecular dynamics (MD) simulations. The KBC is examined at a constant liquid temperature of 85 K in a wide range of nonequilibrium states of vapor. The present investigation is an extension of a previous one by Ishiyama, Yano, and Fujikawa [Phys. Rev. Lett. 95, 084504 (2005)] and provides a more complete form of the KBC. The present KBC includes a thermal accommodation coefficient in addition to evaporation and condensation coefficients, and these coefficients are determined in MD simulations uniquely. The thermal accommodation coefficient shows an anisotropic behavior at the interface for molecular velocities normal versus tangential to the interface. It is also found that the evaporation and condensation coefficients are almost constant in a fairly wide range of nonequilibrium states. The thermal accommodation coefficient of the normal velocity component is almost unity, while that of the tangential component shows a decreasing function of the density of vapor incident on the interface, indicating that the tangential velocity distribution of molecules leaving the interface into the vapor phase may deviate from the tangential parts of the Maxwell velocity distribution at the liquid temperature. A mechanism for the deviation of the KBC from the isotropic Maxwell KBC at the liquid temperature is discussed in terms of anisotropic energy relaxation at the interface. The liquid temperature dependence of the present KBC is also discussed. PMID- 24229189 TI - Crystal growth in a channel: pulsating fingers, merry-go-round patterns, and seesaw dynamics. AB - We perform phase-field simulations of unsteady crystal growth in a three dimensional capillary. Motivated by the appearance of chirality-symmetry breaking periodic states in our preceding study, we here focus on more general dynamic states. Most of these are obtained in the limit of isotropic surface tension, but we test genericity by looking at a few cases with weak anisotropy. Whereas steady states are similar for all channel shapes studied so far, including channels with circular, hexagonal, quadratic, and triangular cross sections, there is a stronger dependence on the cross section for time-dependent states. Various oscillatory modes are identified and discussed, including rotating and swinging patterns as well as pulsating modes containing one, two, and four fingers, respectively. PMID- 24229190 TI - Force and flux relations for flows of ionic solutions between parallel plates with porous and charged layers. AB - We derive coefficients of the electrokinetic coupling matrix (chi(11), chi(12), and chi(21)) for the flow of an ionic solution through a parallel-plate geometry having porous and charged layers grafted onto a solid surface with a known potential and demonstrate Onsager reciprocity for the cross terms (i.e., chi(12)=chi(21)). Our results enable the prediction of system outputs in the solid-porous-fluid system from parameters that are either known or may be measured and inferred. These electrokinetic coupling coefficients are in terms of the potential, phi, and fixed charge, rho(f), only, removing dependence on field gradients and fluid velocity. Additionally, we present simplified expressions of these coupling coefficients in limiting regions of the parameter space. Away from these limits, we present numerical results demonstrating the facility of our functional form for facile numerical approximation and report the utility and accuracy of our analytical approximations. PMID- 24229191 TI - Quasi-one-dimensional thermal breakage. AB - Breakage is generally understood in mechanical terms, yet nanostructures can rupture not only under external loads but also via thermal activation. Here we treat in a general framework the statistical mechanics of thermally induced breakage at the nanoscale for one-dimensional systems. We test it on a simple approximation and find that the probability of breakage controls distinct regimes, characterized by sharp crossovers and narrow peaks in the thermal fluctuations and specific heat. Our work provides predictions on clustering of new phases, of relevance in nanofabrication. PMID- 24229192 TI - Capillary fracture of soft gels. AB - A liquid droplet resting on a soft gel substrate can deform that substrate to the point of material failure, whereby fractures develop on the gel surface that propagate outwards from the contact line in a starburst pattern. In this paper, we characterize (i) the initiation process, in which the number of arms in the starburst is controlled by the ratio of the surface tension contrast to the gel's elastic modulus, and (ii) the propagation dynamics showing that once fractures are initiated they propagate with a universal power law L[proportional]t(3/4). We develop a model for crack initiation by treating the gel as a linear elastic solid and computing the deformations within the substrate from the liquid-solid wetting forces. The elastic solution shows that both the location and the magnitude of the wetting forces are critical in providing a quantitative prediction for the number of fractures and, hence, an interpretation of the initiation of capillary fractures. This solution also reveals that the depth of the gel is an important factor in the fracture process, as it can help mitigate large surface tractions; this finding is confirmed with experiments. We then develop a model for crack propagation by considering the transport of an inviscid fluid into the fracture tip of an incompressible material and find that a simple energy-conservation argument can explain the observed material-independent power law. We compare predictions for both linear elastic and neo-Hookean solids, finding that the latter better explains the observed exponent. PMID- 24229193 TI - Role of the sample thickness in planar crack propagation. AB - We study the effect of the sample thickness in planar crack front propagation in a disordered elastic medium using the random fuse model. We employ different loading conditions and we test their stability with respect to crack growth. We show that the thickness induces characteristic lengths in the stress enhancement factor in front of the crack and in the stress transfer function parallel to the crack. This is reflected by a thickness-dependent crossover scale in the crack front morphology that goes from from multiscaling to self-affine with exponents, in agreement with line depinning models and experiments. Finally, we compute the distribution of crack avalanches, which is shown to depend on the thickness and the loading mode. PMID- 24229194 TI - Stochastic resonance and dynamic first-order pseudo-phase-transitions in the irreversible growth of thin films under spatially periodic magnetic fields. AB - We study the irreversible growth of magnetic thin films under the influence of spatially periodic fields by means of extensive Monte Carlo simulations. We find first-order pseudo-phase-transitions that separate a dynamically disordered phase from a dynamically ordered phase. By analogy with time-dependent oscillating fields applied to Ising-type models, we qualitatively associate this dynamic transition with the localization-delocalization transition of spatial hysteresis loops. Depending on the relative width of the magnetic film L compared to the wavelength of the external field lambda, different transition regimes are observed. For small systems (L < lambda), the transition is associated with the standard stochastic resonance regime, while for large systems (L > lambda), the transition is driven by anomalous stochastic resonance. The origin of the latter is identified as due to the emergence of an additional relevant length scale, namely, the roughness of the spin domain switching interface. The distinction between different stochastic resonance regimes is discussed at length both qualitatively by means of snapshot configurations and quantitatively via residence-length and order-parameter probability distributions. PMID- 24229195 TI - Nematic molecular core flexibility and chiral induction. AB - Electroclinic measurements, in which an applied electric field E induces a rotation Deltatheta ([proportional]E) of the liquid crystal director about the electric field axis in a chiral environment, were performed on several configurationally achiral liquid crystals in the presence of an imposed helical director profile. This imposed twist establishes a chiral symmetry environment for the liquid crystal. It was observed that a conformationally racemic mesogen possessing a flexible phenyl benzoate core exhibits a measurable electroclinic response in the nematic phase. On the other hand, when the phenyl benzoate mesogen is mixed with a mesogen containing a rigid, conformationally achiral core (fluorenone), or with a racemic dopant with an axially chiral core that mimics a mesogen having rigid right- and left-handed conformations (2,2'-spirobiindan-1,1' dione), the magnitudes of the electroclinic responses were found to decrease sharply, apparently going to zero when extrapolated to the pure 2,2'-spirobiindan 1,1'-dione or fluorenone limit. (Note that neither of these additives possesses a nematic phase.). The results suggest that the flexibility of the core and its ability to deracemize conformationally in order to compensate the elastic energy cost of the imposed twist is the primary mechanism behind the observed electroclinic response. PMID- 24229196 TI - High-resolution birefringence investigation of octylcyanobiphenyl (8CB): an upper bound on the discontinuity at the smectic-A to nematic phase transition. AB - We report optical birefringence data by two different methods with high temperature resolution for octylcyanobiphenyl (8CB) near the smectic-A to nematic (Sm-A-N) phase transition temperature T(AN). Within the resolution of our experiments, we find that the Sm-A-N phase transition is continuous. For a possible discontinuity in the orientational order parameter S(T) at T(AN), we arrive at an upper limit of 0.0002, which is substantially smaller than other estimates in literature, but consistent with the value of 0.00008 derived from the upper limit of the latent heat from high-resolution adiabatic scanning calorimetry (ASC), which is itself consistent with the Halperin-Lubensky-Ma theory. The temperature derivative of the order parameter exhibits a power law divergence with a critical exponent that is consistent with the value alpha = 0.31 +/- 0.03 for the specific heat capacity obtained by ASC. PMID- 24229197 TI - Phases and properties of nanocomposites of hydrogen-bonded liquid crystals and carbon nanotubes. AB - We investigated a series of nanocomposites, built of the hydrogen-bonded liquid crystal (LC) p-n-heptyloxybenzoic acid (7OBA) and single-walled carbon nanotubes (SWCNTs) by optical microtexture analysis and other complementary methods. The surface orientation strength of the LC cell and the bulk interaction of the dimeric LC molecules with the SWCNTs turn out to mainly govern the type (symmetry), thermal stability, and chirality of the LC states induced in these nanocomposites. As a result, a cascade of phase transitions and phases not typical for pristine 7OBA were observed and additionally confirmed by temperature dependent Raman spectroscopy and differential scanning calorimetry. The most effective SWCNT concentrations in the LC matrix, ensuring both the necessary conformability between these materials and induction of liquid crystal phases with unique optical and electro-optical properties, were found to be in the range of 0.01-0.007 wt%. Reversal of smectic phases into reentrant nematic states as well as induction of chirality in all LC phases were observed in the SWCNT-7OBA nanocomposite, even though pure 7OBA is typically achiral. However, our most intriguing result is the detection below the reentrant nematic of a triclinic smectic-C(G) phase, which is chiral and biaxial, and exhibits bulk ferroelectricity. PMID- 24229198 TI - Twisted quasiperiodic textures of biaxial nematic liquid crystals. AB - Textures (i.e., smooth space nonuniform distributions of the order parameter) in biaxial nematics turned out to be much more complex and interesting than expected. Scanning the literature we find only a very few publications on this topic. Thus, the immediate motivation of the present paper is to develop a systematic procedure to study, classify, and visualize possible textures in biaxial nematics. Based on the elastic energy of a biaxial nematic (written in the most simple form that involves the least number of phenomenological parameters) we derive and solve numerically the Lagrange equations of the first kind. It allows one to visualize the solutions and offers a deep insight into their geometrical and topological features. Performing Fourier analysis we find some particular textures possessing two or more characteristic space periods (we term such solutions quasiperiodic ones because the periods are not necessarily commensurate). The problem is not only of intellectual interest but also of relevance to optical characteristics of the liquid-crystalline textures. PMID- 24229199 TI - Dynamic arrest of nematic liquid-crystal colloid networks. AB - We report interesting self-assembly structures of nematic liquid-crystal colloid (NLCC) networks, which are arrested during cooling from the isotropic temperature to room temperature. The NLCC is composed of sterically stabilized colloidal particles and a nematic liquid crystal (NLC) with nematic-isotropic transition temperature (T_{NI}) that is much higher than those of previously studied 4-Cyano 4'-pentylbiphenyl and N-(4-Methoxybenzylidene)-4-butylaniline. We find that the structure of NLCCs depends on T(NI), cooling rates, and boundary conditions, varying from cellular network to hierarchical fern structures in different length scales. Our time-lapse study shows that the transition from the cellular network to the fern structure directly corresponds to the transition from a spinodal demixing to a nucleation-and-growth mechanism. PMID- 24229200 TI - Bundling in brushes of directed and semiflexible polymers. AB - We explore the effect of an attractive interaction between parallel-aligned polymers which are perpendicularly grafted on a substrate. Such an attractive interaction could be due to, e.g., reversible cross-links. The competition between permanent grafting favoring a homogeneous state of the polymer brush and the attraction, which tends to induce in-plane collapse of the aligned polymers, gives rise to an instability of the homogeneous phase to a bundled state. In this latter state the in-plane translational symmetry is spontaneously broken and the density is modulated with a finite wavelength, which is set by the length scale of transverse fluctuations of the grafted polymers. We analyze the instability for two models of aligned polymers: directed polymers with line tension epsilon and weakly bending chains with bending stiffness kappa. PMID- 24229201 TI - Microphase separation in comblike liquid-crystalline diblock copolymers. AB - The interplay between liquid crystallinity and microphase separation in comblike liquid-crystalline diblock copolymers is examined via a Brazovskii-type phenomenological model using both analytical and numerical calculations. For symmetric diblock copolymers we determine a critical electric field that is required to tilt the orientation of the constituent liquid crystals of the polymer side chains in the microphase-separated lamellar state. Such electrically induced reorientation of the liquid-crystal molecules can lead to substantially large changes of lamellar periodicity. Our numerical results show that highly aligned polymer lamellar domains can self-assemble when the liquid-crystal ordering precedes microphase separation, and that weak electric fields can be used to direct the self-assembly process due to the dielectric anisotropy of the liquid-crystal side chains. We also find that phase separation of asymmetric diblock copolymers can coexist with a network of liquid-crystal nematic orientations, with domain morphology depending on the details of copolymer and liquid-crystal coupling. PMID- 24229202 TI - Self-consistent field theory and numerical scheme for calculating the phase diagram of wormlike diblock copolymers. AB - This paper concerns establishing a theoretical basis and numerical scheme for studying the phase behavior of AB diblock copolymers made of wormlike chains. The general idea of a self-consistent field theory is the combination of the mean field approach together with a statistical weight that describes the configurational properties of a polymer chain. In recent years, this approach has been extensively used for structural prediction of block copolymers, based on the Gaussian-model description of a polymer chain. The wormlike-chain model has played an important role in the description of polymer systems, covering the semiflexible-to-rod crossover of the polymer properties and the highly stretching regime, which the Gaussian-chain model has difficulties to describe. Although the idea of developing a self-consistent field theory for wormlike chains could be traced back to early development in polymer physics, the solution of such a theory has been limited due to technical difficulties. In particular, a challenge has been to develop a numerical algorithm enabling the calculation of the phase diagram containing three-dimensional structures for wormlike AB diblock copolymers. This paper describes a computational algorithm that combines a number of numerical tricks, which can be used for such a calculation. A phase diagram covering major parameter areas was constructed for the wormlike-chain system and reported by us, where the ratio between the total length and the persistence length of a constituent polymer is suggested as another tuning parameter for the microphase-separated structures; all detailed technical issues are carefully addressed in the current paper. PMID- 24229203 TI - Crossover to surface flow in supercooled unentangled polymer films. AB - We study the driven flow of an unentangled glassy polymer film with a free upper surface and supported below by a substrate using nonequilibrium molecular dynamics simulations based on a bead-spring model. Above the glass transition temperature T(g), simple Poiseuille laminar flow is observed with the film mobility defined as the flow current density per unit pressure gradient scaling as h(3) with the film thickness h. Below T(g), the film mobility becomes independent of h, signifying surface transport. This is in full agreement with recent experiments on the time evolution of capillary waves in polystyrene films supported by silica. A mobile layer is found responsible for the surface transport, as previously conjectured. Our result also shows that it has a velocity profile decaying exponentially into the bulk. PMID- 24229204 TI - Cooperativity length scale in nanocomposites: interfacial and confinement effects. AB - Interfacial and confinement effects on the evolution of cooperativity on approaching the glass transition have been studied in poly(propylenecoethylene) functionalized with diethylmaleate, polyethylene 1,4-cyclohexylenedimethylene terephthalate glycol and their nanocomposites with montmorillonite. A small increase of the structural dynamic cooperativity, a weak alteration of the temperature dependence of the characteristic relaxation frequency, and no changes in the glass transition temperature observed in poly(propylenecoethylene)-based samples can be rationalized in terms of interfacial interactions between polymer and exfoliated clay. On the other hand, confinement of polymer chains in the galleries of clay (intercalated nanocomposite) produces a strong reduction of cooperativity, of the temperature dependence of the characteristic relaxation frequency, and of the glass transition temperature in polyethylene 1,4 cyclohexylenedimethylene terephthalate glycol samples. Finally, by investigating the temperature dependence of a generalized fragility and of cooperativity, we evidenced that fragility of glass formers is determined not only by cooperativity. PMID- 24229205 TI - Cis-trans dynamical asymmetry in driven polymer translocation. AB - During polymer translocation driven by, e.g., voltage drop across a nanopore, the segments in the cis side are incessantly pulled into the pore, which are then pushed out of it into the trans side. This pulling and pushing of polymer segments are described in the continuum level by nonlinear transport processes known, respectively, as fast and slow diffusions. By matching solutions of both sides through the mass conservation across the pore, we provide a physical basis for the cis and trans dynamical asymmetry, a feature repeatedly reported in recent numerical simulations. We then predict how the total driving force is dynamically allocated between cis (pulling) and trans (pushing) sides, demonstrating that the trans-side event adds a weak finite-chain length effect to the dynamical scaling. PMID- 24229206 TI - Nonlinear mechanics of thermoreversibly associating dendrimer glasses. AB - We model the mechanics of associating trivalent dendrimer network glasses with a focus on their energy dissipation properties. Various combinations of sticky bond (SB) strength and kinetics are employed. The toughness (work to fracture) of these systems displays a surprising deformation-protocol dependence; different association parameters optimize different properties. In particular, "strong, slow" SBs optimize strength, while "weak, fast" SBs optimize ductility via self healing during deformation. We relate these observations to breaking, reformation, and partner switching of SBs during deformation. These studies point the way to creating associating-polymer network glasses with tailorable mechanical properties. PMID- 24229207 TI - Simulation of electron paramagnetic resonance spectra of spin-labeled molecules from replica-exchange molecular dynamics. AB - We report a general approach for the simulation of the electron paramagnetic resonance (EPR) spectra of spin labels attached to peptides and proteins directly from replica-exchange molecular dynamics (REMD) trajectories. Conventional MD trajectories are generally inadequate for the prediction of EPR line shapes since the label can become trapped in one or more of a set of rotameric states, thus preventing both conformational sampling and accurate estimates of the exchange rates between different rotamers. The advantage of using REMD is its ability to provide both efficient conformational sampling and kinetic information for spin label dynamics. Our approach is illustrated with spin-labeled peptide. This approach to REMD-EPR simulation paves the way for the wider application of MD modeling to the simulation and interpretation of EPR spectra of spin-labeled molecules. PMID- 24229208 TI - Memory, bias, and correlations in bidirectional transport of molecular-motor driven cargoes. AB - Molecular motors are specialized proteins that perform active, directed transport of cellular cargoes on cytoskeletal filaments. In many cases, cargo motion powered by motor proteins is found to be bidirectional, and may be viewed as a biased random walk with fast unidirectional runs interspersed with slow tug-of war states. The statistical properties of this walk are not known in detail, and here, we study memory and bias, as well as directional correlations between successive runs in bidirectional transport. We show, based on a study of the direction-reversal probabilities of the cargo using a purely stochastic (tug-of war) model, that bidirectional motion of cellular cargoes is, in general, a correlated random walk. In particular, while the motion of a cargo driven by two oppositely pulling motors is a Markovian random walk, memory of direction appears when multiple motors haul the cargo in one or both directions. In the latter case, the Markovian nature of the underlying single-motor processes is hidden by internal transitions between degenerate run and pause states of the cargo. Interestingly, memory is found to be a nonmonotonic function of the number of motors. Stochastic numerical simulations of the tug-of-war model support our mathematical results and extend them to biologically relevant situations. PMID- 24229209 TI - Quantitative analysis of the flexibility effect of cisplatin on circular DNA. AB - We study the effects of cisplatin on the circular configuration of DNA using atomic force microscopy (AFM) and observe that the DNA gradually transforms to a complex configuration with an intersection and interwound structures from a circlelike structure. An algorithm is developed to extract the configuration profiles of circular DNA from AFM images and the radius of gyration is used to describe the flexibility of circular DNA. The quantitative analysis of the circular DNA demonstrates that the radius of gyration gradually decreases and two processes on the change of flexibility of circular DNA are found as the cisplatin concentration increases. Furthermore, a model is proposed and discussed to explain the mechanism for understanding the complicated interaction between DNA and cisplatin. PMID- 24229210 TI - Interaction function of oscillating coupled neurons. AB - Large scale simulations of electrically coupled neuronal oscillators often employ the phase coupled oscillator paradigm to understand and predict network behavior. We study the nature of the interaction between such coupled oscillators using weakly coupled oscillator theory. By employing piecewise linear approximations for phase response curves and voltage time courses and parametrizing their shapes, we compute the interaction function for all such possible shapes and express it in terms of discrete Fourier modes. We find that reasonably good approximation is achieved with four Fourier modes that comprise of both sine and cosine terms. PMID- 24229211 TI - Theoretical study of a molecular turbine. AB - We present an analytic and stochastic simulation study of a molecular engine working with a flux of particles as a turbine. We focus on the physical observables of velocity, flux, power, and efficiency. The control parameters are the external conservative force and the particle densities. We revise a simpler previous study by using a more realistic model containing multiple equidistant vanes complemented by stochastic simulations of the particles and the turbine. Here we show that the effect of the thermal fluctuations into the flux and the efficiency of these nanometric devices are relevant to the working scale of the system. The stochastic simulations of the Brownian motion of the particles and turbine support the simplified analytical calculations performed. PMID- 24229212 TI - Moderate stem-cell telomere shortening rate postpones cancer onset in a stochastic model. AB - Mammalian cells are restricted from proliferating indefinitely. Telomeres at the end of each chromosome are shortened at cell division and when they reach a critical length, the cell will enter permanent cell cycle arrest-a state known as senescence. This mechanism is thought to be tumor suppressing, as it helps prevent precancerous cells from dividing uncontrollably. Stem cells express the enzyme telomerase, which elongates the telomeres, thereby postponing senescence. However, unlike germ cells and most types of cancer cells, stem cells only express telomerase at levels insufficient to fully maintain the length of their telomeres, leading to a slow decline in proliferation potential. It is not yet fully understood how this decline influences the risk of cancer and the longevity of the organism. We here develop a stochastic model to explore the role of telomere dynamics in relation to both senescence and cancer. The model describes the accumulation of cancerous mutations in a multicellular organism and creates a coherent theoretical framework for interpreting the results of several recent experiments on telomerase regulation. We demonstrate that the longest average cancer-free lifespan before cancer onset is obtained when stem cells start with relatively long telomeres that are shortened at a steady rate at cell division. Furthermore, the risk of cancer early in life can be reduced by having a short initial telomere length. Finally, our model suggests that evolution will favor a shorter than optimal average cancer-free lifespan in order to postpone cancer onset until late in life. PMID- 24229213 TI - Neuronal growth as diffusion in an effective potential. AB - Current understanding of neuronal growth is mostly qualitative, as the staggering number of physical and chemical guidance cues involved prohibit a fully quantitative description of axonal dynamics. We report on a general approach that describes axonal growth in vitro, on poly-D-lysine-coated glass substrates, as diffusion in an effective external potential, representing the collective contribution of all causal influences on the growth cone. We use this approach to obtain effective growth rules that reveal an emergent regulatory mechanism for axonal pathfinding on these substrates. PMID- 24229214 TI - Closing the loop: lamellipodia dynamics from the perspective of front propagation. AB - We develop a simple physical model that captures the large-scale lamellipodia dynamics in crawling cells and explains the observed spectrum of fish keratocytes behavior. The main ingredients in this description are the geometrical evolution of the lamellipodium leading edge, the dynamic remodeling of the actin network, and the interconnection between them. We deviate from existing theoretical works and consider the lamellipodium leading edge as a propagating front. The agreement of our model with experimental works suggests that the large-scale morphological and migration features exhibited by keratocyte cells are a direct consequence of the closed feedback loop between the shape of the leading edge and the density of the actin network. PMID- 24229215 TI - Topology and structural self-organization in folded proteins. AB - Topological methods are indispensable in theoretical studies of particle physics, condensed matter physics, and gravity. These powerful techniques have also been applied to biological physics. For example, knowledge of DNA topology is pivotal to the understanding as to how living cells function. Here, the biophysical repertoire of topological methods is extended, with the aim to understand and characterize the global structure of a folded protein. For this, the elementary concept of winding number of a vector field on a plane is utilized to introduce a topological quantity called the folding index of a crystallographic protein. It is observed that in the case of high resolution protein crystals, the folding index, when evaluated over the entire length of the crystallized protein backbone, has a very clear and strong propensity towards integer values. The observation proposes that the way how a protein folds into its biologically active conformation is a structural self-organization process with a topological facet that relates to the concept of solitons. It is proposed that the folding index has a potential to become a useful tool for the global, topological characterization of the folding pathways. PMID- 24229216 TI - Optimal mapping of x-ray laser diffraction patterns into three dimensions using routing algorithms. AB - Coherent diffractive imaging with x-ray free-electron lasers (XFEL) promises high resolution structure determination of noncrystalline objects. Randomly oriented particles are exposed to XFEL pulses for acquisition of two-dimensional (2D) diffraction snapshots. The knowledge of their orientations enables 3D imaging by multiview reconstruction, combining 2D diffraction snapshots in different orientations. Here we introduce a globally optimal algorithm that can infer these orientations. We apply it to experimental XFEL data of nanoparticles and so determine their 3D electron density. PMID- 24229217 TI - Erythrocyte hemodynamics in stenotic microvessels: a numerical investigation. AB - This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 MUm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders. PMID- 24229218 TI - Dynamical structure underlying inverse stochastic resonance and its implications. AB - We investigate inverse stochastic resonance (ISR), a recently reported phenomenon in which the spiking activity of a Hodgkin-Huxley model neuron subject to external noise exhibits a pronounced minimum as the noise intensity increases. We clarify the mechanism that underlies ISR and show that its most surprising features are a consequence of the dynamical structure of the model. Furthermore, we show that the ISR effect depends strongly on the procedures used to measure it. Our results are important for the experimentalist who seeks to observe the ISR phenomenon. PMID- 24229219 TI - Adaptation controls synchrony and cluster states of coupled threshold-model neurons. AB - We analyze zero-lag and cluster synchrony of delay-coupled nonsmooth dynamical systems by extending the master stability approach, and apply this to networks of adaptive threshold-model neurons. For a homogeneous population of excitatory and inhibitory neurons we find (i) that subthreshold adaptation stabilizes or destabilizes synchrony depending on whether the recurrent synaptic excitatory or inhibitory couplings dominate, and (ii) that synchrony is always unstable for networks with balanced recurrent synaptic inputs. If couplings are not too strong, synchronization properties are similar for very different coupling topologies, i.e., random connections or spatial networks with localized connectivity. We generalize our approach for two subpopulations of neurons with nonidentical local dynamics, including bursting, for which activity-based adaptation controls the stability of cluster states, independent of a specific coupling topology. PMID- 24229220 TI - Efficient local behavioral-change strategies to reduce the spread of epidemics in networks. AB - It has recently become established that the spread of infectious diseases between humans is affected not only by the pathogen itself but also by changes in behavior as the population becomes aware of the epidemic, for example, social distancing. It is also well known that community structure (the existence of relatively densely connected groups of vertices) in contact networks influences the spread of disease. We propose a set of local strategies for social distancing, based on community structure, that can be employed in the event of an epidemic to reduce the epidemic size. Unlike most social distancing methods, ours do not require individuals to know the disease state (infected or susceptible, etc.) of others, and we do not make the unrealistic assumption that the structure of the entire contact network is known. Instead, the recommended behavior change is based only on an individual's local view of the network. Each individual avoids contact with a fraction of his/her contacts, using knowledge of his/her local network to decide which contacts should be avoided. If the behavior change occurs only when an individual becomes ill or aware of the disease, these strategies can substantially reduce epidemic size with a relatively small cost, measured by the number of contacts avoided. PMID- 24229221 TI - Epidemic threshold and topological structure of susceptible-infectious susceptible epidemics in adaptive networks. AB - The interplay between disease dynamics on a network and the dynamics of the structure of that network characterizes many real-world systems of contacts. A continuous-time adaptive susceptible-infectious-susceptible (ASIS) model is introduced in order to investigate this interaction, where a susceptible node avoids infections by breaking its links to its infected neighbors while it enhances the connections with other susceptible nodes by creating links to them. When the initial topology of the network is a complete graph, an exact solution to the average metastable-state fraction of infected nodes is derived without resorting to any mean-field approximation. A linear scaling law of the epidemic threshold tau(c) as a function of the effective link-breaking rate omega is found. Furthermore, the bifurcation nature of the metastable fraction of infected nodes of the ASIS model is explained. The metastable-state topology shows high connectivity and low modularity in two regions of the tau,omega plane for any effective infection rate tau>tau(c): (i) a "strongly adaptive" region with very high omega and (ii) a "weakly adaptive" region with very low omega. These two regions are separated from the other half-open elliptical-like regions of low connectivity and high modularity in a contour-line-like way. Our results indicate that the adaptation of the topology in response to disease dynamics suppresses the infection, while it promotes the network evolution towards a topology that exhibits assortative mixing, modularity, and a binomial-like degree distribution. PMID- 24229222 TI - Controlling traffic jams by time modulating the safety distance. AB - The possibility of controlling traffic dynamics by applying high-frequency time modulation of traffic flow parameters is studied. It is shown that the region of the car density where the uniform (free) flow is unstable changes in the presence of time modulation compared with the unmodulated case. This region shrinks when the speed-up of cars does not exceed some critical value and expands in the opposite case. The flux of the time-modulated flow is an increasing function of the amplitude of the modulation for traffic flows whose density is larger than 1/h where h is the safety distance in the nonmodulated case, while it is a decreasing function in the opposite case. In other words, the safety distance time modulation facilitates car propagation in the case when the mean distance between cars in the congestive traffic is less than h and hinders it when the neighboring cars in the flow are well separated. A link between a microscopic description and the macroscopic fundamental diagram is established. PMID- 24229223 TI - Mutual selection in time-varying networks. AB - Time-varying networks play an important role in the investigation of the stochastic processes that occur on complex networks. The ability to formulate the development of the network topology on the same time scale as the evolution of the random process is important for a variety of applications, including the spreading of diseases. Past contributions have investigated random processes on time-varying networks with a purely random attachment mechanism. The possibility of extending these findings towards a time-varying network that is driven by mutual attractiveness is explored in this paper. Mutual attractiveness models are characterized by a linking function that describes the probability of the existence of an edge, which depends mutually on the attractiveness of the nodes on both ends of that edge. This class of attachment mechanisms has been considered before in the fitness-based complex networks literature but not on time-varying networks. Also, the impact of mutual selection is investigated alongside opinion formation and epidemic outbreaks. We find closed-form solutions for the quantities of interest using a factorizable linking function. The voter model exhibits an unanticipated behavior as the network never reaches consensus in the case of mutual selection but stays forever in its initial macroscopic configuration, which is a further piece of evidence that time-varying networks differ markedly from their static counterpart with respect to random processes that take place on them. We also find that epidemic outbreaks are accelerated by uncorrelated mutual selection compared to previously considered random attachment. PMID- 24229224 TI - Observability and coarse graining of consensus dynamics through the external equitable partition. AB - Using the intrinsic relationship between the external equitable partition (EEP) and the spectral properties of the graph Laplacian, we characterize convergence and observability properties of consensus dynamics on networks. In particular, we establish the relationship between the original consensus dynamics and the associated consensus of the quotient graph under varied initial conditions, and characterize the asymptotic convergence to the synchronization manifold under nonuniform input signals. We also show that the EEP with respect to a node can reveal nodes in the graph with an increased rate of asymptotic convergence to the consensus value, as characterized by the second smallest eigenvalue of the quotient Laplacian. Finally, we show that the quotient graph preserves the observability properties of the full graph and how the inheritance by the quotient graph of particular aspects of the eigenstructure of the full Laplacian underpins the observability and convergence properties of the system. PMID- 24229225 TI - Opportunistic migration in spatial evolutionary games. AB - We study evolutionary games in a spatial diluted grid environment in which agents strategically interact locally but can also opportunistically move to other positions within a given migration radius. Using the imitation of the best rule for strategy revision, it is shown that cooperation may evolve and be stable in the Prisoner's Dilemma game space for several migration distances but only for small game interaction radius while the Stag Hunt class of games become fully cooperative. We also show that only a few trials are needed for cooperation to evolve, i.e., searching costs are not an issue. When the stochastic Fermi strategy update protocol is used cooperation cannot evolve in the Prisoner's Dilemma if the selection intensity is high in spite of opportunistic migration. However, when imitation becomes more random, fully or partially cooperative states are reached in all games for all migration distances tested and for short to intermediate interaction radii. PMID- 24229226 TI - Explosive synchronization in weighted complex networks. AB - The emergence of dynamical abrupt transitions in the macroscopic state of a system is currently a subject of the utmost interest. Given a set of phase oscillators networking with a generic wiring of connections and displaying a generic frequency distribution, we show how combining dynamical local information on frequency mismatches and global information on the graph topology suggests a judicious and yet practical weighting procedure which is able to induce and enhance explosive, irreversible, transitions to synchronization. We report extensive numerical and analytical evidence of the validity and scalability of such a procedure for different initial frequency distributions, for both homogeneous and heterogeneous networks, as well as for both linear and nonlinear weighting functions. We furthermore report on the possibility of parametrically controlling the width and extent of the hysteretic region of coexistence of the unsynchronized and synchronized states. PMID- 24229227 TI - Observability transitions in correlated networks. AB - Yang, Wang, and Motter [Phys. Rev. Lett. 109, 258701 (2012)] analyzed a model for network observability transitions in which a sensor placed on a node makes the node and the adjacent nodes observable. The size of the connected components comprising the observable nodes is a major concern of the model. We analyze this model in random heterogeneous networks with degree correlation. With numerical simulations and analytical arguments based on generating functions, we find that negative degree correlation makes networks more observable. This result holds true both when the sensors are placed on nodes one by one in a random order and when hubs preferentially receive the sensors. Finally, we numerically optimize networks with a fixed degree sequence with respect to the size of the largest observable component. Optimized networks have negative degree correlation induced by the resulting hub-repulsive structure; the largest hubs are rarely connected to each other, in contrast to the rich-club phenomenon of networks. PMID- 24229228 TI - Community core detection in transportation networks. AB - This work analyzes methods for the identification and the stability under perturbation of a territorial community structure with specific reference to transportation networks. We considered networks of commuters for a city and an insular region. In both cases, we have studied the distribution of commuters' trips (i.e., home-to-work trips and vice versa). The identification and stability of the communities' cores are linked to the land-use distribution within the zone system, and therefore their proper definition may be useful to transport planners. PMID- 24229229 TI - Communicability in temporal networks. AB - A first-principles approach to quantify the communicability between pairs of nodes in temporal networks is proposed. It corresponds to the imaginary-time propagator of a quantum random walk in the temporal network, which accounts for unique structural and temporal characteristics of both streaming and nonstreaming temporal networks. The influence of the system's temperature on the perdurability of information and how the communicability identifies patterns of communication hidden in the temporal and topological structure of the networks are also studied for synthetic and real-world systems. PMID- 24229230 TI - Structural and functional discovery in dynamic networks with non-negative matrix factorization. AB - Time series of graphs are increasingly prevalent in modern data and pose unique challenges to visual exploration and pattern extraction. This paper describes the development and application of matrix factorizations for exploration and time varying community detection in time-evolving graph sequences. The matrix factorization model allows the user to home in on and display interesting, underlying structure and its evolution over time. The methods are scalable to weighted networks with a large number of time points or nodes and can accommodate sudden changes to graph topology. Our techniques are demonstrated with several dynamic graph series from both synthetic and real-world data, including citation and trade networks. These examples illustrate how users can steer the techniques and combine them with existing methods to discover and display meaningful patterns in sizable graphs over many time points. PMID- 24229231 TI - Spectral clustering with epidemic diffusion. AB - Spectral clustering is widely used to partition graphs into distinct modules or communities. Existing methods for spectral clustering use the eigenvalues and eigenvectors of the graph Laplacian, an operator that is closely associated with random walks on graphs. We propose a spectral partitioning method that exploits the properties of epidemic diffusion. An epidemic is a dynamic process that, unlike the random walk, simultaneously transitions to all the neighbors of a given node. We show that the replicator, an operator describing epidemic diffusion, is equivalent to the symmetric normalized Laplacian of a reweighted graph with edges reweighted by the eigenvector centralities of their incident nodes. Thus, more weight is given to edges connecting more central nodes. We describe a method that partitions the nodes based on the componentwise ratio of the replicator's second eigenvector to the first and compare its performance to traditional spectral clustering techniques on synthetic graphs with known community structure. We demonstrate that the replicator gives preference to dense, clique-like structures, enabling it to more effectively discover communities that may be obscured by dense intercommunity linking. PMID- 24229232 TI - Origin of complexity and conditional predictability in cellular automata. AB - A simple mechanism for the emergence of complexity in cellular automata out of predictable dynamics is described. This leads to introduce the concept of conditional predictability for systems whose trajectory can only be piecewise known. The mechanism is used to construct a cellular automaton model for discrete chimeralike states, where synchrony and incoherence in an ensemble of identical oscillators coexist. The incoherent region is shown to have a periodicity that is three orders of magnitude longer than the period of the synchronous oscillation. PMID- 24229233 TI - Edge removal balances preferential attachment and triad closing. AB - Most network formation analysis studies are centered on edge addition. However, edges in real world networks often have a rapid turnover with a large number of edges added and removed between each node addition or removal steps. In such a case, quasiequilibrium is obtained between edge addition and deletion. Edges have been shown to be added to nodes with a high degree and between pairs of nodes with a high number of common neighbors. If not balanced by a degree dependent edge removal, the preference for high degree nodes and node pairs with many common neighbors is expected to increase the average degree of high degree nodes and their clustering coefficient until very large cliques will be formed. Since such large cliques are not formed in real world networks, we conclude that the edge removal probability around high degree nodes and between node pairs with many common neighbors should be higher than around other nodes. We here show the existence of such a balancing mechanism through the relation between the future edge removal probability around nodes and their degree and a similar relation between the edge removal probability and the number of common neighbors of node pairs. In some networks, this preferential detachment process represents an explicit saturation process, and in others, it represents a random deletion process accompanied by a sublinear edge preferential attachment process. A more complex mechanism emerges in directed networks where the preferential detachment can be proportional to the in and out degrees of the nodes involved. In such networks, preferential detachment is stronger for the incoming edges than for the outgoing edges. We hypothesize multiple possible mechanisms that could explain this phenomenon. PMID- 24229234 TI - Extraction of self-diffusivity in systems with nondiffusive short-time behavior. AB - We consider a toy model that captures the short-time nondiffusive behavior seen in many physical systems, to study the extraction of self-diffusivity from particle trajectories. We propose and evaluate a simple method to automatically detect the transition to diffusive behavior. We simulate the toy model to generate data sets of varying quality and test different methods of extracting the self-diffusion coefficient and characterizing its uncertainty. We find that weighted least-squares with statistical bootstrap is the most accurate and efficient means for analyzing the trajectory data. The analysis suggests an iterative recipe for designing simulations to conform to a specified level of accuracy. PMID- 24229235 TI - Extracting connectivity from dynamics of networks with uniform bidirectional coupling. AB - In the study of networked systems, a method that can extract information about how the individual nodes are connected with one another would be valuable. In this paper, we present a method that can yield such information of network connectivity using measurements of the dynamics of the nodes as the only input data. Our method is built upon a noise-induced relation between the Laplacian matrix of the network and the dynamical covariance matrix of the nodes, and applies to networked dynamical systems in which the coupling between nodes is uniform and bidirectional. Using examples of different networks and dynamics, we demonstrate that the method can give accurate connectivity information for a wide range of noise amplitude and coupling strength. Moreover, we can calculate a parameter Delta using again only the input of time-series data, and assess the accuracy of the extracted connectivity information based on the value of Delta. PMID- 24229236 TI - Emergence and scaling of synchronization in moving-agent networks with restrictive interactions. AB - In fields such as robotics and sensor networks, synchronization among mobile and dynamic agents is a basic task. We articulate an effective strategy to achieve synchronization in dynamic networks of moving chaotic agents. Our counterintuitive idea is to restrict agents' ability to interact with each other, which can be implemented by designating a finite number of fixed zones in the space, in which agents are allowed to interact with each other but agents outside the zones are deprived of the ability of mutual interaction. Our setting is thus different from the one used in existing works on synchronization of mobile agents where each agent is associated with an interacting zone that moves with the agent. We find, through a mathematical analysis, that an optimal interval exists in the interaction probability, where stable synchronization emerges. An inverse square-root scaling law is uncovered which relates the interval with the system size, i.e., the total number of moving agents. Extensive numerical support for physical spaces of one, two, and three dimensions is provided. PMID- 24229237 TI - Optimal rates for electron transfer in Marcus theory. AB - We examine electron transfer between two quantum states in the presence of a dissipative environment represented as a set of independent harmonic oscillators. For this simple model, the Marcus transfer rates can be derived from the equations of motion for electronic operators and we show that these rates are associated to an explicit expression for the environment correlation time. We demonstrate that as a manifestation of the Goldilocks principle, the optimal transfer is governed by a single parameter which is equal to just the inverse square root of 2. PMID- 24229238 TI - Effects of local population structure in a reaction-diffusion model of a contact process on metapopulation networks. AB - We investigate the effects of local population structure in reaction-diffusion processes representing a contact process (CP) on metapopulations represented as complex networks. Considering a model in which the nodes of a large scale network represent local populations defined in terms of a homogeneous graph, we show by means of extensive numerical simulations that the critical properties of the reaction-diffusion system are independent of the local population structure, even when this one is given by a ordered linear chain. This independence is confirmed by the perfect matching between numerical critical exponents and the results from a heterogeneous mean-field theory suited, in principle, to describe situations of local homogeneous mixing. The analysis of several variations of the reaction diffusion process allows us to conclude the independence from population structure of the critical properties of CP-like models on metapopulations, and thus of the universality of the reaction-diffusion description of this kind of models. PMID- 24229239 TI - Dynamic patterns and their interactions in networks of excitable elements. AB - Formation of localized propagating patterns is a fascinating self-organizing phenomenon that happens in a wide range of spatially extended, excitable systems in which individual elements have resting, activated, and refractory states. Here we study a type of stochastic three-state excitable network model that has been recently developed; this model is able to generate a rich range of pattern dynamics, including localized wandering patterns and localized propagating patterns with crescent shapes and long-range propagation. The collective dynamics of these localized patterns have anomalous subdiffusive dynamics before symmetry breaking and anomalous superdiffusive dynamics after that, showing long-range spatiotemporal coherence in the system. In this study, the stability of the localized wandering patterns is analyzed by treating an individual localized pattern as a subpopulation to develop its average response function. This stability analysis indicates that when the average refractory period is greater than a certain value, there are too many elements in the refractory state after being activated to allow the subpopulation to support a self-sustained pattern; this is consistent with symmetry breaking identified by using an order parameter. Furthermore, in a broad parameter space, the simple network model is able to generate a range of interactions between different localized propagating patterns including repulsive collisions and partial and full annihilations, and interactions between localized propagating patterns and the refractory wake behind others; in this study, these interaction dynamics are systematically quantified based on their relative propagation directions and the resultant angles between them before and after their collisions. These results suggest that the model potentially provides a modeling framework to understand the formation of localized propagating patterns in a broad class of systems with excitable properties. PMID- 24229240 TI - Spectral methods for community detection and graph partitioning. AB - We consider three distinct and well-studied problems concerning network structure: community detection by modularity maximization, community detection by statistical inference, and normalized-cut graph partitioning. Each of these problems can be tackled using spectral algorithms that make use of the eigenvectors of matrix representations of the network. We show that with certain choices of the free parameters appearing in these spectral algorithms the algorithms for all three problems are, in fact, identical, and hence that, at least within the spectral approximations used here, there is no difference between the modularity- and inference-based community detection methods, or between either and graph partitioning. PMID- 24229241 TI - Ising models on the regularized Apollonian network. AB - We investigate the critical properties of Ising models on a regularized Apollonian network (RAN), here defined as a kind of Apollonian network in which the connectivity asymmetry associated with its corners is removed. Different choices for the coupling constants between nearest neighbors are considered and two different order parameters are used to detect the critical behavior. While ordinary ferromagnetic and antiferromagnetic models on a RAN do not undergo a phase transition, some antiferrimagnetic models show an interesting infinite order transition. All results are obtained by an exact analytical approach based on iterative partial tracing of the Boltzmann factor as an intermediate step for the calculation of the partition function and the order parameters. PMID- 24229242 TI - Synchronization in random balanced networks. AB - Characterizing the influence of network properties on the global emerging behavior of interacting elements constitutes a central question in many areas, from physical to social sciences. In this article we study a primary model of disordered neuronal networks with excitatory-inhibitory structure and balance constraints. We show how the interplay between structure and disorder in the connectivity leads to a universal transition from trivial to synchronized stationary or periodic states. This transition cannot be explained only through the analysis of the spectral density of the connectivity matrix. We provide a low dimensional approximation that shows the role of both the structure and disorder in the dynamics. PMID- 24229243 TI - Loss of stability of a solitary wave through exciting a cnoidal wave on a Fermi Pasta-Ulam ring. AB - The spatiotemporal propagation behavior of a solitary wave is investigated on a Fermi-Pasta-Ulam ring. We observe the emergence of a cnoidal wave excited by the solitary wave. The cnoidal wave may coexist with the solitary wave for a long time associated with the periodic exchange of energy between these two nonlinear waves. The module of the cnoidal wave, which is considered as an indicator of the nonlinearity, is found to oscillate with the same period of the energy exchange. After the stage of coexistence, the interaction between these two nonlinear waves leads to the destruction of the cnoidal wave by the radiation of phonons. Finally, the interaction of the solitary wave with phonons leads to the loss of stability of the solitary wave. PMID- 24229244 TI - Multipulse phase resetting curves. AB - In this paper, we introduce and study systematically, in terms of phase response curves, the effect of dual-pulse excitation on the dynamics of an autonomous oscillator. Specifically, we test the deviations from linear summation of phase advances resulting from two small perturbations. We analytically derive a correction term, which generally appears for oscillators whose intrinsic dimensionality is >1. The nonlinear correction term is found to be proportional to the square of the perturbation. We demonstrate this effect in the Stuart Landau model and in various higher dimensional neuronal models. This deviation from the superposition principle needs to be taken into account in studies of networks of pulse-coupled oscillators. Further, this deviation could be used in the verification of oscillator models via a dual-pulse excitation. PMID- 24229245 TI - Deformations of third-order Peregrine breather solutions of the nonlinear Schrodinger equation with four parameters. AB - We present a new representation of solutions of the one-dimensional nonlinear focusing Schrodinger equation (NLS) as a quotient of two determinants. This formulation gives in the case of the order 3, new solutions with four parameters. This gives a very efficient procedure to construct families of quasirational solutions of the NLS equation and to describe the apparition of multirogue waves. With this method, we construct analytical expressions of four-parameters solutions; when all these parameters are equal to 0, we recover the Peregrine breather of order 3. It makes possible with this four-parameters representation, to generate all the types of patterns for the solutions, like the triangular configurations or the ring structures. PMID- 24229246 TI - Nonlinear vibrational resonance. AB - We examine the nonlinear response of a bistable system driven by a high-frequency force to a low-frequency weak field. It is shown that the rapidly varying temporal oscillation breaks the spatial symmetry of the centrosymmetric potential. This gives rise to a finite nonzero response at the second harmonic of the low-frequency field, which can be optimized by an appropriate choice of vibrational amplitude of the high-frequency field close to that for the linear response. The potential implications of the nonlinear vibrational resonance are analyzed. PMID- 24229247 TI - Parameter estimation and control for a neural mass model based on the unscented Kalman filter. AB - Recent progress in Kalman filters to estimate states and parameters in nonlinear systems has provided the possibility of applying such approaches to neural systems. We here apply the nonlinear method of unscented Kalman filters (UKFs) to observe states and estimate parameters in a neural mass model that can simulate distinct rhythms in electroencephalography (EEG) including dynamical evolution during epilepsy seizures. We demonstrate the efficiency of the UKF in estimating states and parameters. We also develop an UKF-based control strategy to modulate the dynamics of the neural mass model. In this strategy the UKF plays the role of observing states, and the control law is constructed via the estimated states. We demonstrate the feasibility of using such a strategy to suppress epileptiform spikes in the neural mass model. PMID- 24229248 TI - Taming rogue waves in vector Bose-Einstein condensates. AB - Using gauge transformation method, we generate rogue waves for the two-component Bose-Einstein condensates (BECs) governed by the symmetric coupled Gross Pitaevskii (GP) equations and study their dynamics. We also suggest a mechanism to tame the rogue waves either by manipulating the scattering length through Feshbach resonance or the trapping frequency, a phenomenon not witnessed in the domain of BECs, and we believe that these results may have wider ramifications in the management of rogons. PMID- 24229249 TI - Emergence of antiphase bursting in two populations of randomly spiking elements. AB - Animal locomotion activity relies on the generation and control of coordinated periodic actions in a central pattern generator (CPG). A core element of many CPGs responsible for the rhythm generation is a pair of reciprocally coupled neuron populations. Recent interest in the development of highly reduced models of CPG networks is motivated by utilization of CPG models in applications for biomimetic robotics. This paper considers the use of a reduced model in the form of a discrete time system to study the emergence of antiphase bursting activity in two reciprocally coupled populations evoked by the postinhibitory rebound effect. PMID- 24229250 TI - Onset of chaotic dynamics in neural networks. AB - A neural-network model is proposed as a test bed for the characterization of the chaotic dynamics emerging in a context where the coupling is, on the average, neither excitatory nor inhibitory. The proposed discrete-time model generalizes within a single framework two different setups previously studied in the literature. With the help of theoretical mean field arguments and numerical simulations on GPUs, we characterize the transition and show that the chaotic dynamics is extensive (i.e., that the number of active degrees of freedom is proportional to the network size) from the very beginning. Besides the coupling strength, two parameters play a crucial role: (1) one controls the local dissipation and determines the shape of the initial part of the Lyapunov spectrum as well as the shape of the correlation function; (2) the other, which corresponds to the amplitude of an effective random field, determines the nature of the transition. PMID- 24229251 TI - Influence of the history force on inertial particle advection: gravitational effects and horizontal diffusion. AB - We analyze the effect of the Basset history force on the sedimentation or rising of inertial particles in a two-dimensional convection flow. When memory effects are neglected, the system exhibits rich dynamics, including periodic, quasiperiodic, and chaotic attractors. Here we show that when the full advection dynamics is considered, including the history force, both the nature and the number of attractors change, and a fractalization of their basins of attraction appears. In particular, we show that the history force significantly weakens the horizontal diffusion and changes the speed of sedimentation or rising. The influence of the history force is dependent on the size of the advected particles, being stronger for larger particles. PMID- 24229252 TI - Stabilization of standing waves through time-delay feedback. AB - Standing waves are studied as solutions of a complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms. The onset is described as an instability of the uniform oscillations with respect to spatially periodic perturbations. The solution of the standing wave pattern is given analytically and studied through simulations. PMID- 24229253 TI - Exploding dissipative solitons in reaction-diffusion systems. AB - We show that exploding dissipative solitons can arise in a reaction-diffusion system for a range of parameters. As a function of a vorticity parameter, we observe a sequence of transitions from oscillatory localized states via meandering dissipative solitons to exploding dissipative solitons propagating in one direction for long times followed by the reverse cascade back to oscillatory localized states. While exploding dissipative solitons are known from the cubic quintic complex Ginzburg-Landau (CGL) equation, propagating exploding dissipative solitons appear to require for their existence a system of lower symmetry such as the reaction-diffusion model studied here. PMID- 24229254 TI - Accessible solitons in complex Ginzburg-Landau media. AB - We construct dissipative spatial solitons in one- and two-dimensional (1D and 2D) complex Ginzburg-Landau (CGL) equations with spatially uniform linear gain; fully nonlocal complex nonlinearity, which is proportional to the integral power of the field times the harmonic-oscillator (HO) potential, similar to the model of "accessible solitons;" and a diffusion term. This CGL equation is a truly nonlinear one, unlike its actually linear counterpart for the accessible solitons. It supports dissipative spatial solitons, which are found in a semiexplicit analytical form, and their stability is studied semianalytically, too, by means of the Routh-Hurwitz criterion. The stability requires the presence of both the nonlocal nonlinear loss and diffusion. The results are verified by direct simulations of the nonlocal CGL equation. Unstable solitons spontaneously spread out into fuzzy modes, which remain loosely localized in the effective complex HO potential. In a narrow zone close to the instability boundary, both 1D and 2D solitons may split into robust fragmented structures, which correspond to excited modes of the 1D and 2D HOs in the complex potentials. The 1D solitons, if shifted off the center or kicked, feature persistent swinging motion. PMID- 24229255 TI - Onset patterns in a simple model of localized parametric forcing. AB - We investigate pattern selection at onset in a parametrically and inhomogeneously forced partial differential equation obtained by generalizing Mathieu's equation to include spatial interactions. No separation of scales is assumed. The proposed model is directly relevant to the case of parametrically forced surface waves, such as cross-waves, excited by the horizontal vibration of a fluid, where the forcing is localized to a finite region near the endwall or wavemaker. The availability of analytical solutions in the limit of piecewise constant forcing allows us investigate in detail the dependence of selected eigenfunctions on spatial detuning, forcing width, damping, boundary conditions, and container size. A wide range of onset patterns are located and described, many of which are rotated, modulated, or both, and deviate far from simple crosswise oriented standing waves. The linear selection mechanisms governing this multiplicity of potential onset patterns are discussed. PMID- 24229256 TI - Exploring rigidly rotating vortex configurations and their bifurcations in atomic Bose-Einstein condensates. AB - In the present work, we consider the problem of a system of few vortices N <= 5 as it emerges from its experimental realization in the field of atomic Bose Einstein condensates. Starting from the corresponding equations of motion for an axially symmetric trapped condensate, we use a two-pronged approach in order to reveal the configuration space of the system's preferred dynamical states. We use a Monte Carlo method parametrizing the vortex particles by means of hyperspherical coordinates and identifying the minimal energy ground states thereof for N=2,...,5 and different vortex particle angular momenta. We then complement this picture with a dynamical system analysis of the possible rigidly rotating states. The latter reveals a supercritical and subcritical pitchfork, as well as saddle-center bifurcations that arise, exposing the full wealth of the problem even for such low-dimensional cases. By corroborating the results of the two methods, it becomes fairly transparent which branch the Monte Carlo approach selects for different values of the angular momentum that is used as a bifurcation parameter. PMID- 24229257 TI - One cannot hear the density of a drum (and further aspects of isospectrality). AB - It is well known that certain pairs of planar domains have the same spectra of the Laplacian operator. We prove that these domains are still isospectral for a wider class of physical problems, including the cases of heterogeneous drums and quantum billiards in an external field. In particular we show that the isospectrality is preserved when the density or the potential is symmetric under reflections along the folding lines of the domain. These results are also confirmed numerically using the finite-difference method: We find that the pairs of numerical matrices obtained in the discretization are exactly isospectral up to machine precision. PMID- 24229258 TI - Effective equations for matter-wave gap solitons in higher-order transversal states. AB - We demonstrate that an important class of nonlinear stationary solutions of the three-dimensional (3D) Gross-Pitaevskii equation (GPE) exhibiting nontrivial transversal configurations can be found and characterized in terms of an effective one-dimensional (1D) model. Using a variational approach we derive effective equations of lower dimensionality for BECs in (m,n(r)) transversal states (states featuring a central vortex of charge m as well as n(r) concentric zero-density rings at every z plane) which provides us with a good approximate solution of the original 3D problem. Since the specifics of the transversal dynamics can be absorbed in the renormalization of a couple of parameters, the functional form of the equations obtained is universal. The model proposed finds its principal application in the study of the existence and classification of 3D gap solitons supported by 1D optical lattices, where in addition to providing a good estimate for the 3D wave functions it is able to make very good predictions for the MU(N) curves characterizing the different fundamental families. We have corroborated the validity of our model by comparing its predictions with those from the exact numerical solution of the full 3D GPE. PMID- 24229259 TI - Amplitude-mediated chimera states. AB - We investigate the possibility of obtaining chimera state solutions of the nonlocal complex Ginzburg-Landau equation (NLCGLE) in the strong coupling limit when it is important to retain amplitude variations. Our numerical studies reveal the existence of a variety of amplitude-mediated chimera states (including stationary and nonstationary two-cluster chimera states) that display intermittent emergence and decay of amplitude dips in their phase incoherent regions. The existence regions of the single-cluster chimera state and both types of two-cluster chimera states are mapped numerically in the parameter space of C(1) and C(2), the linear and nonlinear dispersion coefficients, respectively, of the NLCGLE. They represent a new domain of dynamical behavior in the well explored rich phase diagram of this system. The amplitude-mediated chimera states may find useful applications in understanding spatiotemporal patterns found in fluid flow experiments and other strongly coupled systems. PMID- 24229260 TI - Back-and-forth micromotion of aqueous droplets in a dc electric field. AB - Recently, it was reported that an aqueous droplet in an oil phase exhibited rhythmic back-and-forth motion under stationary dc voltage on the order of 100 V. Here, we demonstrate that the threshold voltage for inducing such oscillation is successfully decreased to the order of 10 V through downsizing of the experimental system. Notably, the threshold electric field tends to decrease with a nonlinear scaling relationship accompanied by the downsizing. We derive a simple theoretical model to interpret the system size dependence of the threshold voltage. This model equation suggests the unique effect of additional noise, which is qualitatively characterized as a coherent resonance by an actual experiment as a kind of coherent resonance. Our result would provide insight into the construction of micrometer-sized self-commutating motors and actuators in microfluidic and micromechanical devices. PMID- 24229261 TI - Experimental evidence of using a circularly polarized electric field to control spiral turbulence. AB - Experimental evidence of the use of a circularly polarized electric field to control the spiral turbulence in a reaction-diffusion system is presented. The spiral turbulence obtained in the Belousov-Zhabotinsky reaction is shown to be forced into ordered stable spiral waves or "targetlike" waves by a circularly polarized electric field with appropriate frequency and intensity. An Arnold's tongue-shaped control phase diagram is obtained, illustrating the resonance essence of the control. PMID- 24229262 TI - Global interactions, information flow, and chaos synchronization. AB - We investigate the relationship between the emergence of chaos synchronization and the information flow in dynamical systems possessing homogeneous or heterogeneous global interactions whose origin can be external (driven systems) or internal (autonomous systems). By employing general models of coupled chaotic maps for such systems, we show that the presence of a homogeneous global field, either external or internal, for all times is not indispensable for achieving complete or generalized synchronization in a system of chaotic elements. Complete synchronization can also appear with heterogeneous global fields; it does not requires the simultaneous sharing of the field by all the elements in a system. We use the normalized mutual information and the information transfer between global and local variables to characterize complete and generalized synchronization. We show that these information measures can characterize both types of synchronized states and also allow us to discern the origin of a global interaction field. A synchronization state emerges when a sufficient amount of information provided by a field is shared by all the elements in the system, on the average over long times. Thus, the maximum value of the top-down information transfer can be used as a predictor of synchronization in a system, as a parameter is varied. PMID- 24229263 TI - Criterion for the emergence of explosive synchronization transitions in networks of phase oscillators. AB - The emergence of explosive synchronization transitions in networks of phase oscillators recently has become one of the most interesting topics. It is widely believed that the large frequency mismatch of a pair of oscillators (also known as disassortativity in frequency) is a direct cause of an explosive synchronization. It is found that, besides the disassortativity in frequency, the disassortativity in node degree also shows up in connection with the first-order synchronization transition. In this paper, we simulate the Kuramoto model on top of a family of networks with different degree-degree and frequency-frequency correlation patterns. Results show that only when the degrees and natural frequencies of the network's nodes are both disassortative can an explosive synchronization occur. PMID- 24229264 TI - Multifractality, stickiness, and recurrence-time statistics. AB - We identify the fine structure of resonance islands and the stickiness in chaos through recurrence time statistics (RTS), which is based on the concept of Poincare recurrences. The projection of recurrence time statistics onto the phase space does give relevant information on the hierarchical and microstructures of the chaotic beach around the islands of a near-integrable system, the annular billiard. These microstructures interfere in the effective transport of a particle in the phase space, which can be observed through RTS. This technique proves also to be a powerful tool to describe the homoclinic tangle of the manifolds within the chaotic sea. PMID- 24229265 TI - Reactivity boundaries for chemical reactions associated with higher-index and multiple saddles. AB - Reactivity boundaries that divide the origin and destination of trajectories are of crucial importance to reveal the mechanism of reactions, which was recently found to exist robustly even at high energies for index 1 saddles [Phys. Rev. Lett. 105, 048304 (2010)]. Here we revisit the concept of the reactivity boundary and propose a more general definition that can involve a single reaction associated with a bottleneck composed of higher-index saddles and/or several saddle points with different indices, where the normal form theory, based on expansion around a single stationary point, does not work. We numerically demonstrate the reactivity boundary by using a reduced model system of the H(5)(+) cation where the proton exchange reaction takes place through a bottleneck composed of two index 2 saddle points and two index 1 saddle points. The cross section of the reactivity boundary in the reactant region of the phase space reveals which initial conditions are effective in making the reaction happen and thus sheds light on the reaction mechanism. PMID- 24229266 TI - Stability and dynamics of nonautonomous systems with pulsed nonlinearity. AB - We study the dynamics of a class of nonautonomous systems with pulsed nonlinearity that consist of a periodic sequence of linear and nonlinear autonomous systems, each one acting alone in a different time or space interval. We focus on the investigation of control capabilities of such systems in terms of altering their fundamental dynamical properties by appropriate parameter selections. For the case of single oscillators, the stability of the zero solution as well as the phase space topology is shown to drastically depend on parameters such as the frequency of the linear oscillations and the durations of the linear and nonlinear intervals. In cases of chain of coupled oscillators with pulsed onsite nonlinearity, it is shown that appropriate parameter selections can stabilize an otherwise unstable zero background allowing for the existence of dynamically robust localized excitations, whose evolution properties can now be explicitly determined and controlled. PMID- 24229267 TI - Turing pattern formation in the Brusselator system with nonlinear diffusion. AB - In this work we investigate the effect of density-dependent nonlinear diffusion on pattern formation in the Brusselator system. Through linear stability analysis of the basic solution we determine the Turing and the oscillatory instability boundaries. A comparison with the classical linear diffusion shows how nonlinear diffusion favors the occurrence of Turing pattern formation. We study the process of pattern formation both in one-dimensional and two-dimensional spatial domains. Through a weakly nonlinear multiple scales analysis we derive the equations for the amplitude of the stationary patterns. The analysis of the amplitude equations shows the occurrence of a number of different phenomena, including stable supercritical and subcritical Turing patterns with multiple branches of stable solutions leading to hysteresis. Moreover, we consider traveling patterning waves: When the domain size is large, the pattern forms sequentially and traveling wave fronts are the precursors to patterning. We derive the Ginzburg Landau equation and describe the traveling front enveloping a pattern which invades the domain. We show the emergence of radially symmetric target patterns, and, through a matching procedure, we construct the outer amplitude equation and the inner core solution. PMID- 24229268 TI - Composite bound states and broken U(1) symmetry in the chemical-master-equation derivation of the Gray-Scott model. AB - We give a first principles derivation of the stochastic partial differential equations that describe the chemical reactions of the Gray-Scott model (GS): U+2V ->[lambda]3V and V -> [MU]P, U -> [nu]Q, with a constant feed rate for U. We find that the conservation of probability ensured by the chemical master equation leads to a modification of the usual differential equations for the GS model, which now involves two composite fields and also intrinsic noise terms. One of the composites is psi(1) = phi(v)(2), where {phi(v)}(eta) =v is the concentration of the species V and the averaging is over the internal noise eta(u,v,psi(1)). The second composite field is the product of three fields chi = lambdaphi(u)phi(v)(2) and requires a noise source to ensure probability conservation. A third composite psi(2) = phi(u)phi(v) can also be identified from the noise-induced reactions. The Hamiltonian that governs the time evolution of the many-body wave function, associated with the master equation, has a broken U(1) symmetry related to particle number conservation. By expanding around the (broken symmetry) zero-energy solution of the Hamiltonian (by performing a Doi shift) one obtains from our path integral formulation the usual reaction diffusion equation, at the classical level. The Langevin equations that are derived from the chemical master equation have multiplicative noise sources for the density fields phi(u), phi(v),chi that induce higher-order processes such as n -> n scattering for n>3. The amplitude of the noise acting on phi(v) is itself stochastic in nature. PMID- 24229269 TI - Semiclassical description of resonance-assisted tunneling in one-dimensional integrable models. AB - Resonance-assisted tunneling is investigated within the framework of one dimensional integrable systems. We present a systematic recipe, based on Hamiltonian normal forms, to construct one-dimensional integrable models that exhibit resonance island chain structures with accurately controlled sizes and positions of the islands. Using complex classical trajectories that evolve along suitably defined paths in the complex time domain, we construct a semiclassical theory of the resonance-assisted tunneling process. This semiclassical approach yields a compact analytical expression for tunnelling-induced level splittings which is found to be in very good agreement with the exact splittings obtained through numerical diagonalization. PMID- 24229270 TI - Lagrangian statistics across the turbulent-nonturbulent interface in a turbulent plane jet. AB - Lagrangian statistics from millions of particles are used to study the turbulent entrainment mechanism in a direct numerical simulation of a turbulent plane jet at Re(lambda) ~ 110. The particles (tracers) are initially seeded at the irrotational region of the jet near the turbulent shear layer and are followed as they are drawn into the turbulent region across the turbulent-nonturbulent interface (TNTI), allowing the study of the enstrophy buildup and thereby characterizing the turbulent entrainment mechanism in the jet. The use of Lagrangian statistics following fluid particles gives a more correct description of the entrainment mechanism than in previous works since the statistics in relation to the TNTI position involve data from the trajectories of the entraining fluid particles. The Lagrangian statistics for the particles show the existence of a velocity jump and a characteristic vorticity jump (with a thickness which is one order of magnitude greater than the Kolmogorov microscale), in agreement with previous results using Eulerian statistics. The particles initially acquire enstrophy by viscous diffusion and later by enstrophy production, which becomes "active" only deep inside the turbulent region. Both enstrophy diffusion and production near the TNTI differ substantially from inside the turbulent region. Only about 1% of all particles find their way into pockets of irrotational flow engulfed into the turbulent shear layer region, indicating that "engulfment" is not significant for the present flow, indirectly suggesting that the entrainment is largely due to "nibbling" small-scale mechanisms acting along the entire TNTI surface. Probability density functions of particle positions suggests that the particles spend more time crossing the region near the TNTI than traveling inside the turbulent region, consistent with the particles moving tangent to the interface around the time they cross it. PMID- 24229271 TI - Determining the number of fingers in the lifting Hele-Shaw problem. AB - The lifting Hele-Shaw cell flow is a variation of the celebrated radial viscous fingering problem for which the upper cell plate is lifted uniformly at a specified rate. This procedure causes the formation of intricate interfacial patterns. Most theoretical studies determine the total number of emerging fingers by maximizing the linear growth rate, but this generates discrepancies between theory and experiments. In this work, we tackle the number of fingers selection problem in the lifting Hele-Shaw cell by employing the recently proposed maximum amplitude criterion [Dias and Miranda, Phys. Rev. E 88, 013016 (2013)]. Our linear stability analysis accounts for the action of capillary, viscous normal stresses, and wetting effects, as well as the cell confinement. The comparison of our results with very precise laboratory measurements for the total number of fingers shows a significantly improved agreement between theoretical predictions and experimental data. PMID- 24229272 TI - Electrohydrodynamic rotations of a viscous droplet. AB - We report a fluid system which exhibits chaotic dynamics under creeping flow conditions. A droplet in a uniform dc electric field deforms into an ellipsoid that can undergo irregular rotational motions. The nonlinear drop electrohydrodynamics is explained by a theoretical model which includes anisotropy in the polarization relaxation due to drop asphericity and charge convection due to rotational drop flow. PMID- 24229273 TI - Stability of two-layer shear-thinning film flows. AB - The stability of a two-layer film flow of non-Newtonian fluids is studied with a linear temporal approach. Shear-thinning fluids are considered, which follow the four-parameter inelastic Carreau model. A modified Orr-Sommerfeld equation system is obtained, which is solved by using a spectral Tau collocation method based on Chebyshev polynomials. The effects of density and viscosity stratification are considered, as well as the influence of the shear-thinning properties of the fluid. It is found that, when the viscosity is stronger in the upper layer, the base flow and the stability properties are almost not influenced by the change of the shear-thinning properties in this upper layer. In the other situations, the shear-thinning properties have an influence on the different instabilities, the long-wave surface instability and the short- and long-wave interface instabilities. PMID- 24229274 TI - Bifurcations and dynamics in convection with temperature-dependent viscosity in the presence of the O(2) symmetry. AB - We focus on the study of a convection problem in a two-dimensional setup in the presence of the O(2) symmetry. The viscosity in the fluid depends on the temperature as it changes its value abruptly in an interval around a temperature of transition. The influence of the viscosity law on the morphology of the plumes is examined for several parameter settings, and a variety of shapes ranging from spout- to mushroom-shaped are found. We explore the impact of the symmetry on the time evolution of this type of fluid, and we find solutions which are greatly influenced by its presence: at a large aspect ratio and high Rayleigh numbers, traveling waves, heteroclinic connections, and chaotic regimes are found. These solutions, which are due to the presence of symmetry, have not been previously described in the context of temperature-dependent viscosities. However, similarities are found with solutions described in other contexts such as flame propagation problems or convection problems with constant viscosity also in the presence of the O(2) symmetry, thus confirming the determining role of the symmetry in the dynamics. PMID- 24229275 TI - Dynamics of an oscillating bubble in a narrow gap. AB - The complex dynamics of a single bubble of a few millimeters in size oscillating inside a narrow fluid-filled gap between two parallel plates is studied using high-speed videography. Two synchronized high-speed cameras were used to observe both the side and front views of the bubble. The front-view images show bubble expansion and collapse with the formation of concentric dark and bright rings. The simultaneous recordings reveal the mechanism behind these rings. The side view images reveal two different types of collapse behavior of the bubble including a previously unreported collapse phenomenon that is observed as the gap width is changed. At narrow widths, the bubble collapses towards the center of the gap; when the width is increased, the bubble splits before collapsing towards the walls. The bubble dynamics is also observed to be unaffected by the hydrophobic or hydrophilic nature of the plate surface due to the presence of a thin film of liquid between each of the plates and the bubble throughout the bubble lifetime. It is revealed that such systems do not behave as quasi-two dimensional systems; three-dimensional effects are important. PMID- 24229276 TI - Influence of hydrophobic effects on streaming potential. AB - We study the influence of hydrophobic effects on streaming potential mediated flow through a narrow confinement. In a clear departure from the approach used in prior works, we use a phase-field model to capture the hydrophobicity-induced depletion in the near wall region, and express the variation of viscosity and permittivity across the interfacial layer in terms of the phase-field variable. We then use these in the determination of the flow velocity, and highlight the sensitive interplay between the intrinsic length scale of the electrical double layer and that of the depletion in terms of the variations of an effective normalized viscosity that captures the electroviscous effect. We expect that this work will be an important step forward in the realistic continuum modeling of interfacial physics in the particular context of streaming potential mediated flows. PMID- 24229277 TI - Coarse-grained forms for equations describing the microscopic motion of particles in a fluid. AB - Exact equations of motion for the microscopically defined collective density rho(x,t) and the momentum density g(x,t) of a fluid have been obtained in the past starting from the corresponding Langevin equations representing the dynamics of the fluid particles. In the present work we average these exact equations of microscopic dynamics over the local equilibrium distribution to obtain stochastic partial differential equations for the coarse-grained densities with smooth spatial and temporal dependence. In particular, we consider Dean's exact balance equation for the microscopic density of a system of interacting Brownian particles to obtain the basic equation of the dynamic density functional theory with noise. Our analysis demonstrates that on thermal averaging the dependence of the exact equations on the bare interaction potential is converted to dependence on the corresponding thermodynamic direct correlation functions in the coarse grained equations. PMID- 24229278 TI - Generic path for droplet relaxation in microfluidic channels. AB - In two-phase microfluidics, droplets often undergo deformations that drive them away from their circular equilibrium shape. Herein we concentrate on the relaxation of symmetrical deformations to a circle driven by surface tension effects, which are predominant at the micrometer scales. Working in a Hele-Shaw cell, we report a generic pathway for these types of relaxations. We simulate numerically the interface shape evolution and investigate it using linear stability analysis. Finally, we characterize this universal aspect of relaxation using a purely geometrical model that is tested in experiments. PMID- 24229279 TI - Interfacial velocities and capillary pressure gradients during Haines jumps. AB - Drainage is typically understood as a process where the pore space is invaded by a nonwetting phase pore-by-pore, the controlling parameters of which are represented by capillary number and mobility ratio. However, what is less understood and where experimental data are lacking is direct knowledge of the dynamics of pore drainage and the associated intrinsic time scales since the rate dependencies often observed with displacement processes are potentially dependent on these time scales. Herein, we study pore drainage events with a high speed camera in a micromodel system and analyze the dependency of interfacial velocity on bulk flow rate and spatial fluid configurations. We find that pore drainage events are cooperative, meaning that capillary pressure differences which extend over multiple pores directly affect fluid topology and menisci dynamics. Results suggest that not only viscous forces but also capillarity acts in a nonlocal way. Lastly, the existence of a pore morphological parameter where pore drainage transitions from capillary to inertial and/or viscous dominated is discussed followed by a discussion on capillary dispersion and time scale dependencies. We show that the displacement front is disperse when volumetric flow rate is less than the intrinsic time scale for a pore drainage event and becomes sharp when the flow rate is greater than the intrinsic time scale (i.e., overruns the pore drainage event), which clearly shows how pore-scale parameters influence macroscale flow behavior. PMID- 24229280 TI - Rayleigh wave scattering from sessile droplets. AB - Radiation of energy by large-amplitude leaky Rayleigh waves is regarded as one of the key physical mechanisms regulating the actuation and manipulation of droplets in surface acoustic wave (SAW) microfluidic devices. The interaction between a SAW and a droplet is highly complex and is presently the subject of extensive research. This paper investigates the existence of an additional interaction mechanism based on the propagation of quasi-Stoneley waves inside sessile droplets deposited on a solid substrate. In contrast with the leaky Rayleigh wave, the energy of the Stoneley wave is confined within a thin fluid layer in contact with the substrate. The hypothesis is confirmed by three-dimensional finite element simulations and ultrasonic scattering experiments measuring the reflection of Rayleigh waves from droplets of different diameters. Moreover, real time monitoring of the droplet evaporation process reveals a clear correlation between the droplet contact angle and the spectral information of the reflected Rayleigh signal, thus paving the way for ultrasonic measurements of surface tension. PMID- 24229281 TI - Coupled motion of microscale and nanoscale elastic objects in a viscous fluid. AB - We study the coupled dynamics of two closely spaced micron or nanoscale elastic objects immersed in a viscous fluid. The dynamics of the elastic objects are coupled through the motion of the surrounding viscous fluid. We consider two cases: (i) one object is driven externally by an imposed harmonic actuation force and the second object is passive and (ii) both objects are driven by a Brownian force to yield stochastic dynamics. Using a harmonic oscillator approximation for the elastic objects and the unsteady Stokes equations to describe the fluid dynamics, we develop analytical expressions for the amplitude and phase of the displacement of the oscillating objects. For the case of an imposed actuation we use an impulse in force to determine the resulting dynamics over all frequencies. For the Brownian-driven objects the stochastic dynamics are found using the fluctuation-dissipation theorem. We validate our theoretical expressions by comparison with results from finite-element numerical simulations of the complete fluid-solid interaction problem. Our results yield interesting features in the amplitude and phase of the displacement of the elastic objects due to the fluid motion. We find that the dynamics depend on the separation of the objects, a measure of the mass loading due to the fluid, and the frequency parameter which acts as a frequency-based Reynolds number. Our results are valid over the range of parameters typical of micron and nanoscale elastic objects in fluid. The range of dynamics found can be understood in terms of the interplay between the viscous and potential components of the fluid flow field described by the unsteady Stokes equation for an oscillating cylinder. For small values of the frequency parameter, typical of nanoscale elastic objects, the dynamics are overdamped due to the dominance of viscous forces over inertial forces. For moderate and large values of the frequency parameter, typical of micron-scale elastic objects, we find that the dynamics of the fluid-coupled objects exhibits an interesting mode splitting to yield a bimodal signature in the amplitude-frequency plots. We find that the mode splitting can be described using a normal mode analysis containing only potential fluid interactions between the cylinders. PMID- 24229282 TI - Swimming dynamics of bidirectional artificial flagella. AB - We study magnetic artificial flagella whose swimming speed and direction can be controlled using light and magnetic field as external triggers. The dependence of the swimming velocity on the system parameters (e.g., length, stiffness, fluid viscosity, and magnetic field) is explored using a computational framework in which the magnetostatic, fluid dynamic, and solid mechanics equations are solved simultaneously. A dimensionless analysis is carried out to obtain an optimal combination of system parameters for which the swimming velocity is maximal. The swimming direction reversal is addressed by incorporating photoresponsive materials, which in the photoactuated state can mimic natural mastigonemes. PMID- 24229283 TI - Capillary-gravity waves on a liquid film of arbitrary depth: analysis of the wave resistance. AB - We discuss the wave resistance in the case of an externally perturbed viscous liquid film of arbitrary thickness. Emphasis is placed on the dependence of the wave resistance on the film thickness H, the length scale b characterizing the external perturbation, and its velocity V. In particular, the effectiveness of the mechanisms of capillary-gravity waves and the viscous dissipation localized in the vicinity of the perturbation are compared and discussed as functions of H and V. We show that, in general, the wave resistance is a nonmonotonous function of H with a maximum whose amplitude and position depend on b and V. In the case of small H the wave resistance depends on a parameter S proportional V/H(3). We find three different regimes of this parameter in which the wave resistance behaves like S(r) with the exponent r equal to 1, 1/3, and -1. These results are also obtained independently within the thin liquid film approximation. This allows us to assess the range of validity of the thin liquid film approximation in various cases, in particular its dependence on the perturbation length scale b. PMID- 24229284 TI - Three-dimensional continuation study of convection in a tilted rectangular enclosure. AB - A continuation method developed from a three-dimensional spectral finite element code is used to study natural convection in a tilted rectangular cavity. The cavity has its length equal to two times the side of its square cross section and it contains a fluid with a Prandtl number Pr = 1. A detailed bifurcation diagram is first obtained in the case without inclination in order to get the sequence of the different branches of solutions and determine the stable solutions. The focus is then put on the stable solutions in the inclined cavity, when the tilt occurs around its longest axis. The subtle changes induced by the tilt on the convective system are clarified. Three different stable solutions are obtained: the longitudinal roll L- solution (with the same sense of rotation as the inclination angle), which develops smoothly from zero Rayleigh number on the leading branch; the longitudinal roll L+ solution (with a sense of rotation opposite to the inclination angle), which is on a disconnected branch and is stabilized beyond a secondary bifurcation point; the oblique roll O +/- solutions (corresponding to transverse roll solutions perturbed by the longitudinal flow induced by the tilt), which quickly appear beyond saddle-node points on new disconnected branches. The domain of existence of these stable solutions is eventually obtained and described in the Rayleigh number-inclination parameter space. Finally, the Nusselt number is determined as a function of the inclination at a constant Rayleigh number for the different stable solutions. The Nusselt number is maximum at an inclination of 49.55 degrees for the leading longitudinal roll L- solution. PMID- 24229286 TI - Multifractal structure of fully developed turbulence. AB - The appearance of vortex filaments, the power-law dependence of velocity and vorticity correlations and their multiscaling behavior are derived from the Navier-Stokes equation. This is possible due to interpretation of the Navier Stokes equation as an equation with multiplicative noise and remarkable properties of random matrix products. PMID- 24229285 TI - Experimental evidence of temperature gradients in cavitating microflows seeded with thermosensitive nanoprobes. AB - Thermosensitive fluorescent nanoparticles seeded in deionized water combined with confocal microscopy enables thermal mapping over three dimensions of the liquid phase flowing through a microchannel interrupted by a microdiaphragm. This experiment reveals the presence of a strong thermal gradient up to ~10(5) K/m only when hydrodynamic cavitation is present. Here hydrodynamic cavitation is the consequence of high shear rates downstream in the diaphragm. This temperature gradient is located in vortical structures associated with eddies in the shear layers. We attribute such overheating to the dissipation involved by the cavitating flow regime. Accordingly, we demonstrate that the microsizes of the device enhance the intensity of the thermal gap. PMID- 24229287 TI - Self-collimated axial jet seeds from thin accretion disks. AB - We show how an appropriate stationary crystalline structure of the magnetic field can induce a partial fragmentation of the accretion disk, generating an axial jet seed composed of hot plasma twisted in a funnel-like structure due to the rotation of the system. The most important feature we outline is the high degree of collimation, naturally following from the basic assumptions underlying the crystalline structure. The presence of nonzero dissipative effects allows the plasma ejection throughout the axial jet seed and the predicted values of the accretion rate are in agreement with observations. PMID- 24229288 TI - Polarization effect on the relativistic nonlinear dynamics of an intense laser beam propagating in a hot magnetoactive plasma. AB - Nonlinear dynamics of an intense circularly polarized laser beam interacting with a hot magnetized plasma is investigated. Using a relativistic fluid model, a modified nonlinear Schrodinger equation is derived based on a quasineutral approximation, which is valid for hot plasma. Using a three-dimensional model, spatial-temporal development of the laser pulse is investigated. The occurrence of some nonlinear phenomena such as self-focusing, self-modulation, light trapping, and filamentation of the laser pulse is discussed. Also the effect of polarization and external magnetic field on the nonlinear evolution of these phenomena is studied. PMID- 24229289 TI - Mode couplings and resonance instabilities in dust clusters. AB - The normal modes for three to seven particle two-dimensional (2D) dust clusters in a complex plasma are investigated using an N-body simulation. The ion wakefield downstream of each particle is shown to induce coupling between horizontal and vertical modes. The rules of mode coupling are investigated by classifying the mode eigenvectors employing the Bessel and trigonometric functions indexed by order integers (m, n). It is shown that coupling only occurs between two modes with the same m and that horizontal modes having a higher shear contribution exhibit weaker coupling. Three types of resonances are shown to occur when two coupled modes have the same frequency. Discrete instabilities caused by both the first and third type of resonances are verified and instabilities caused by the third type of resonance are found to induce melting. The melting procedure is observed to go through a two-step process with the solid liquid transition closely obeying the Lindemann criterion. PMID- 24229290 TI - Ion collision cross sections and transport coefficients extended to intermediate energies and reduced electric fields for He(2)(+) ions colliding with He. AB - This work is devoted to the calculation of transport coefficients for He(2)(+) ions in gaseous He at intermediate reduced electric fields. These swarm data are of great interest for a better understanding of the mechanisms of formation and propagation of the fast plasma bullets or ionization waves observed in dielectric barrier plasma jet devices. For transport data, the collision cross sections required are determined from several theoretical methods based on quantum, semiclassical, and hybrid approaches and a diatomics-in-molecules model for the potential energy surfaces of He(2)(+). The corresponding collision cross sections are then used in an optimized Monte Carlo code to calculate the ion transport coefficients over a wide range of reduced electric fields extending over the experimental range. Calculated transport coefficients are compared with available experimental data at low electric fields. Moreover, an extrapolation method is used in order to determine the reduced mobility for stronger fields. A critical discussion has been performed on the pertinence and the reliability of these different methods of determination of collision cross sections needed for the calculation of ion transport data. Such ion data will be used in electrohydrodynamic and chemical kinetic models of the low-temperature plasma jet to quantify and to tune the active species production for a better use in biomedical applications. PMID- 24229291 TI - Relativistically induced transparency acceleration of light ions by an ultrashort laser pulse interacting with a heavy-ion-plasma density gradient. AB - The relativistically induced transparency acceleration (RITA) scheme of proton and ion acceleration using laser-plasma interactions is introduced, modeled, and compared to the existing schemes. Protons are accelerated with femtosecond relativistic pulses to produce quasimonoenergetic bunches with controllable peak energy. The RITA scheme works by a relativistic laser inducing transparency [Akhiezer and Polovin, Zh. Eksp. Teor. Fiz 30, 915 (1956); Kaw and Dawson, Phys. Fluids 13, 472 (1970); Max and Perkins, Phys. Rev. Lett. 27, 1342 (1971)] to densities higher than the cold-electron critical density, while the background heavy ions are stationary. The rising laser pulse creates a traveling acceleration structure at the relativistic critical density by ponderomotively [Lindl and Kaw, Phys. Fluids 14, 371 (1971); Silva et al., Phys. Rev. E 59, 2273 (1999)] driving a local electron density inflation, creating an electron snowplow and a co-propagating electrostatic potential. The snowplow advances with a velocity determined by the rate of the rise of the laser's intensity envelope and the heavy-ion-plasma density gradient scale length. The rising laser is incrementally rendered transparent to higher densities such that the relativistic electron plasma frequency is resonant with the laser frequency. In the snowplow frame, trace density protons reflect off the electrostatic potential and get snowplowed, while the heavier background ions are relatively unperturbed. Quasimonoenergetic bunches of velocity equal to twice the snowplow velocity can be obtained and tuned by controlling the snowplow velocity using laser-plasma parameters. An analytical model for the proton energy as a function of laser intensity, rise time, and plasma density gradient is developed and compared to 1D and 2D PIC OSIRIS [Fonseca et al., Lect. Note Comput. Sci. 2331, 342 (2002)] simulations. We model the acceleration of protons to GeV energies with tens-of femtoseconds laser pulses of a few petawatts. The scaling of proton energy with laser power compares favorably to other mechanisms for ultrashort pulses [Schreiber et al., Phys. Rev. Lett. 97, 045005 (2006); Esirkepov et al., Phys. Rev. Lett. 92, 175003 (2004); Silva et al., Phys. Rev. Lett. 92, 015002 (2004); Fiuza et al., Phys. Rev. Lett. 109, 215001 (2012)]. PMID- 24229292 TI - Ion-wake-induced anomaly of dust lattice mode in the presence of an external magnetic field. AB - We report a theoretical investigation of the dust lattice (DL) mode in two dimensional Yukawa crystals in the presence of asymmetric ion flow and an external magnetic field perpendicular to the crystal plane. Two mutually perpendicular modes are found to be coupled due to Lorentz force. Interaction among the dust grains along the vertical direction of ion flow is strongly affected due to the formation of an ion wake. This causes anisotropy in interaction strength along two mutually perpendicular directions. Both hybrid modes are studied as characteristics of different ion flow speeds and magnetic field strengths. The study shows a fluctuation in DL mode frequency driven by the strength of the particle-wake interaction. The effect of ion flow on polarization of the hybrid wave amplitudes is discussed in detail. Results show a possible mechanism of anomalous phase transition in dusty plasma. PMID- 24229293 TI - Heavy ion charge-state distribution effects on energy loss in plasmas. AB - According to dielectric formalism, the energy loss of the heavy ion depends on its velocity and its charge density. Also, it depends on the target through its dielectric function; here the random phase approximation is used because it correctly describes fully ionized plasmas at any degeneracy. On the other hand, the Brandt-Kitagawa (BK) model is employed to depict the projectile charge space distribution, and the stripping criterion of Kreussler et al. is used to determine its mean charge state [Q]. This latter criterion implies that the mean charge state depends on the electron density and temperature of the plasma. Also, the initial charge state of the heavy ion is crucial for calculating [Q] inside the plasma. Comparing our models and estimations with experimental data, a very good agreement is found. It is noticed that the energy loss in plasmas is higher than that in the same cold gas cases, confirming the well-known enhanced plasma stopping (EPS). In this case, EPS is only due to the increase in projectile effective charge Q(eff), which is obtained as the ratio between the energy loss of each heavy ion and that of the proton in the same plasma conditions. The ratio between the effective charges in plasmas and in cold gases is higher than 1, but it is not as high as thought in the past. Finally, another significant issue is that the calculated effective charge in plasmas Q(eff) is greater than the mean charge state [Q], which is due to the incorporation of the BK charge distribution. When estimations are performed without this distribution, they do not fit well with experimental data. PMID- 24229294 TI - Simple determinant representation for rogue waves of the nonlinear Schrodinger equation. AB - We present a simple representation for arbitrary-order rogue wave solution and a study on the trajectories of them explicitly. We find that the trajectories of two valleys on whole temporal-spatial distribution all look "X" -shaped for rogue waves. Additionally, we present different types of high-order rogue wave structures, which could be helpful towards realizing the complex dynamics of rogue waves. PMID- 24229295 TI - Classical scattering of charged particles confined on an inhomogeneous helix. AB - We explore the effects arising due to the coupling of the center of mass and relative motion of two charged particles confined on an inhomogeneous helix with a locally modified radius. It is first proven that a separation of the center of mass and the relative motion is provided if and only if the confining manifold represents a homogeneous helix. In this case, bound states of repulsively Coulomb interacting particles occur. For an inhomogeneous helix, the coupling of the center of mass and relative motion induces an energy transfer between the collective and relative motion, leading to dissociation of initially bound states in a scattering process. Due to the time reversal symmetry, a binding of the particles out of the scattering continuum is thus equally possible. We identify the regimes of dissociation for different initial conditions and provide an analysis of the underlying phase space via Poincare surfaces of section. Bound states inside the inhomogeneity as well as resonant states are identified. PMID- 24229296 TI - Second-harmonic generation for dispersive elastic waves in a discrete granular chain. AB - The propagation of nonlinear compressional waves in a one-dimensional granular chain driven at one end by a harmonic excitation is studied. The chain is described by a Fermi-Pasta-Ulam (FPU) lattice model with quadratic nonlinearity (alpha-FPU model), valid for strong initial compression of the chain by an external static force. A successive approximations method is used to obtain the analytical expressions for the amplitudes of the static displacement field and of the fundamental and second harmonics propagating through the lattice. Both propagating and evanescent second harmonics are shown to influence the nonlinear propagation characteristics of the fundamental frequency. The propagating regime is characterized by a periodic energy transfer between first and second harmonics, resulting from dispersion, which disappears when the second harmonic becomes evanescent. PMID- 24229297 TI - Bright and peaklike pulse solitary waves and analogy with modulational instability in an extended nonlinear Schrodinger equation. AB - The modulational instability (MI) phenomenon in the nonlinear Schrodinger equation (NLSE) extended by two different nonlinear dispersion terms and the gradient term is investigated. We find that the possibility of instability of plane waves depends on the sign of the nonlinear dispersion parameters with regard to the linear dispersion coefficient. In contrast to the basic NLSE, the system may exhibit instability in the defocusing media for amplitude exceeding a critical value depending on the magnitude of the nonlinear dispersion. An additional feature, namely the higher order or the infinite gain band, absent in the NLSE case, may appear and in which MI induces the birth of the nonlinear localized wave (NLW) of different carrier wave numbers. The result of the qualitative investigations of the system's dynamics indicates the existence of the NLW, such as peak, bright, dark, and compact dark solitary waves which can be well predicted by the MI criteria. In addition the nonlinear dispersion induces the existence of a pair of bright-dark solitary waves which is usually exhibited by the coupled NLSEs only, and the pairs of peak-dark and compact dark-bright solitary waves. PMID- 24229298 TI - Rare-event sampling for driven inertial systems via the nonequilibrium distribution function. AB - Recently substantial generalizations have been made to the Yamada-Kawasaki type nonlinear response theory formalism for deterministic dynamics. These provide opportunities to develop new importance sampling techniques against known distribution functions. We exploit this to develop a method of calculating nonequilibrium rate constants across a large free energy barrier, allowing molecular simulations to access far greater time scales. In contrast to existing stochastic methods, we do not merely follow the dynamics forward in time, allowing systems governed by inertial equations of motion to be usefully addressed. We further generalize the Yamada-Kawasaki type formalism to the case of stochastic equations of motion and the resulting nonequilibrium importance sampling method follows straight forwardly. We quantitatively test the method on stochastic and deterministic models, specifically chosen to allow a comparison with reliable, independently obtained data. To do this we consider oscillators in a one-dimensional double well potential. Either side of the well is separated by an energy barrier and the oscillator is driven away from equilibrium by a position dependent temperature profile. The energy barrier is chosen to be low enough that we can still solve the system computationally by brute force. We demonstrate that the results of our method are consistent with those from the brute force simulations to very high accuracy. We also show how our method is more than two orders of magnitude more efficient for the given example than forward flux sampling. PMID- 24229299 TI - Flat histogram diagrammatic Monte Carlo method: calculation of the Green's function in imaginary time. AB - The diagrammatic Monte Carlo (DiagMC) method is a numerical technique which samples the entire diagrammatic series of the Green's function in quantum many body systems. In this work, we incorporate the flat histogram principle in the diagrammatic Monte Carlo method, and we term the improved version the "flat histogram diagrammatic Monte Carlo" method. We demonstrate the superiority of this method over the standard DiagMC in extracting the long-imaginary-time behavior of the Green's function, without incorporating any a priori knowledge about this function, by applying the technique to the polaron problem. PMID- 24229300 TI - Modeling steady-state dynamics of macromolecules in exponential-stretching flow using multiscale molecular-dynamics-multiparticle-collision simulations. AB - We introduce a method to obtain steady-state uniaxial exponential-stretching flow of a fluid (akin to extensional flow) in the incompressible limit, which enables us to study the response of suspended macromolecules to the flow by computer simulations. The flow field in this flow is defined by v(x) = epsilonx, where v(x) is the velocity of the fluid and epsilon is the stretch flow gradient. To eliminate the effect of confining boundaries, we produce the flow in a channel of uniform square cross section with periodic boundary conditions in directions perpendicular to the flow, but simultaneously maintain uniform density of fluid along the length of the tube. In experiments a perfect elongational flow is obtained only along the axis of symmetry in a four-roll geometry or a filament stretching rheometer. We can reproduce flow conditions very similar to extensional flow near the axis of symmetry by exponential-stretching flow; we do this by adding the right amounts of fluid along the length of the flow in our simulations. The fluid particles added along the length of the tube are the same fluid particles which exit the channel due to the flow; thus mass conservation is maintained in our model by default. We also suggest a scheme for possible realization of exponential-stretching flow in experiments. To establish our method as a useful tool to study various soft matter systems in extensional flow, we embed (i) spherical colloids with excluded volume interactions (modeled by the Weeks-Chandler potential) as well as (ii) a bead-spring model of star polymers in the fluid to study their responses to the exponential-stretched flow and show that the responses of macromolecules in the two flows are very similar. We demonstrate that the variation of number density of the suspended colloids along the direction of flow is in tune with our expectations. We also conclude from our study of the deformation of star polymers with different numbers of arms f that the critical flow gradient epsilon(c) at which the star undergoes the coil-to stretch transition is independent of f for f = 2,5,10, and 20. PMID- 24229301 TI - Dynamics of solutes with hydrodynamic interactions: comparison between Brownian dynamics and stochastic rotation dynamics simulations. AB - The dynamics of particles in solution or suspension is influenced by thermal fluctuations and hydrodynamic interactions. Several mesoscale methods exist to account for these solvent-induced effects such as Brownian dynamics with hydrodynamic interactions and hybrid molecular dynamics-stochastic rotation dynamics methods. Here we compare two ways of coupling solutes to the solvent with stochastic rotation dynamics (SRD) to Brownian dynamics with and without explicit hydrodynamic interactions. In the first SRD scheme [SRD with collisional coupling (CC)] the solutes participate in the collisional step with the solvent and in the second scheme [SRD with central force coupling (CFC)] the solutes interact through direct forces with the solvent, generating slip boundary conditions. We compare the transport coefficients of neutral and charged solutes in a model system obtained by these simulation schemes. Brownian dynamics without hydrodynamic interactions is used as a reference to quantify the influence of hydrodynamics on the transport coefficients as modeled by the different methods. We show that, in the dilute range, the SRD CFC method provides results similar to those of Brownian dynamics with hydrodynamic interactions for the diffusion coefficients and for the electrical conductivity. The SRD CC scheme predicts diffusion coefficients close to those obtained by Brownian dynamic simulations without hydrodynamic interactions, but accounts for part of the influence of hydrodynamics on the electrical conductivity. PMID- 24229302 TI - Bottom-up construction of interaction models of non-Markovian dissipative particle dynamics. AB - We derive the equation of motion for non-Markovian dissipative particle dynamics (NMDPD) by introducing the history effects on the time evolution of the system. Our formulation is based on the generalized Langevin equation, which describes the motions of the centers of mass of clusters comprising microscopic particles. The mean, friction, and fluctuating forces in the NMDPD model are directly constructed from an underlying molecular dynamics (MD) system without any scaling procedure. For the validation of our formulation, we construct NMDPD models from high-density Lennard-Jones systems, in which the typical time scales of the coarse-grained particle motions and the fluctuating forces are not fully separable. The NMDPD models reproduce the temperatures, diffusion coefficients, and viscosities of the corresponding MD systems more accurately than the dissipative particle dynamics models based on a Markovian approximation. Our results suggest that the NMDPD method is a promising alternative for simulating mesoscale flows where a Markovian approximation is not valid. PMID- 24229303 TI - Color-gradient lattice Boltzmann model for simulating droplet motion with contact angle hysteresis. AB - Lattice Boltzmann method (LBM) is an effective tool for simulating the contact line motion due to the nature of its microscopic dynamics. In contact-line motion, contact-angle hysteresis is an inherent phenomenon, but it is neglected in most existing color-gradient based LBMs. In this paper, a color-gradient based multiphase LBM is developed to simulate the contact-line motion, particularly with the hysteresis of contact angle involved. In this model, the perturbation operator based on the continuum surface force concept is introduced to model the interfacial tension, and the recoloring operator proposed by Latva-Kokko and Rothman is used to produce phase segregation and resolve the lattice pinning problem. At the solid surface, the color-conserving wetting boundary condition [Hollis et al., IMA J. Appl. Math. 76, 726 (2011)] is applied to improve the accuracy of simulations and suppress spurious currents at the contact line. In particular, we present a numerical algorithm to allow for the effect of the contact-angle hysteresis, in which an iterative procedure is used to determine the dynamic contact angle. Numerical simulations are conducted to verify the developed model, including the droplet partial wetting process and droplet dynamical behavior in a simple shear flow. The obtained results are compared with theoretical solutions and experimental data, indicating that the model is able to predict the equilibrium droplet shape as well as the dynamic process of partial wetting and thus permits accurate prediction of contact-line motion with the consideration of contact-angle hysteresis. PMID- 24229304 TI - Monte Carlo renormalization-group analysis of percolation. AB - We describe a Monte Carlo renormalization group approach to the calculation of critical behavior for percolation models. This approach can be utilized to determine the renormalized bond probabilities and the values of the critical exponents. We illustrate the method for two-dimensional bond percolation, but the method is also applicable to other percolation models and other dimensions. PMID- 24229305 TI - Ionization cross section data of nitrogen, methane, and propane for light ions and electrons and their suitability for use in track structure simulations. AB - Track structure Monte Carlo simulations are frequently applied in micro- and nanodosimetry to calculate the radiation transport in detail. The use of a well validated set of cross section data in such simulation codes ensures accurate calculations of transport parameters, such as ionization yields. These cross section data are, however, scarce and often discrepant when measured by different groups. This work surveys literature data on ionization and charge-transfer cross sections of nitrogen, methane, and propane for electrons, protons, and helium particles, focusing on the energy range between 100 keV and 20 MeV. Based on the evaluated data, different models for the parametrization of the cross section data are implemented in the code ptra, developed for simulating proton and alpha particle transport in an ion-counting nanodosimeter. The suitability of the cross section data is investigated by comparing the calculated mean ionization cluster size and energy loss with experimental results in either nitrogen or propane. For protons, generally good agreement between measured and simulated data is found when the Rudd model is used in ptra. For alpha particles, however, a considerable influence of different parametrizations of cross sections for ionization and charge transfer is observed. The ptra code using the charge-transfer data is, nevertheless, successfully benchmarked by the experimental data for the calculation of nanodosimetric quantities, but remaining discrepancies still have to be further investigated (up to 13% lower energy loss and 19% lower mean ionization cluster size than in the experiment). A continuation of this work should investigate data for the energy loss per interaction as well as differential cross section data of nitrogen and propane. Interpolation models for ionization and charge-transfer data are proposed. The Barkas model, frequently used for a determination of the effective charge in the ionization cross section, significantly underestimates both the energy loss (by up to 19%) and the mean ionization cluster size (up to 65%) for alpha particles. It is, therefore, not recommended for particle-track simulations. PMID- 24229306 TI - Lorentz transformation of blackbody radiation. AB - We present a simple calculation of the Lorentz transformation of the spectral distribution of blackbody radiation at temperature T. Here we emphasize that T is the temperature in the blackbody rest frame and does not change. We thus avoid the confused and confusing question of how temperature transforms. We show by explicit calculation that at zero temperature the spectral distribution is invariant. At finite temperature we find the well-known result familiar in discussions of the 2.7 K cosmic radiation. PMID- 24229307 TI - X-ray cross-correlation analysis of liquid crystal membranes in the vicinity of the hexatic-smectic phase transition. AB - We present an x-ray study of liquid crystal membranes in the vicinity of the hexatic-smectic phase transition by means of angular x-ray cross-correlation analysis. By applying two-point angular-intensity cross-correlation functions to the measured series of diffraction patterns the parameters of bond-orientational (BO) order in hexatic phase were directly determined. The temperature dependence of the positional correlation lengths was analyzed as well. The obtained correlation lengths show larger values for the higher-order Fourier components of BO order. These findings indicate a strong coupling between BO and positional order. PMID- 24229308 TI - Fluorescent beads disintegrate actin networks. AB - We studied the influence of fluorescent polystyrene beads on both entangled and cross-linked actin networks. Thermal bead fluctuations were observed via video particle tracking and analyzed with one-point microrheology. Illumination of fluorescent beads with their appropriate excitation wavelength leads to a drastic softening of actin gels. Other wavelengths and bright field microscopy do not increase thermal bead fluctuations. This effect cannot be significantly reduced by adding common oxygen scavengers. We conclude that the usage of fluorescent beads impairs results when studying the microrheology of actin networks. PMID- 24229309 TI - Spatial ranges of driving forces are a key determinant of protein folding cooperativity and rate diversity. AB - The physical basis of two-state-like folding transitions and the tremendous diversity in folding rates is elucidated by directly simulating the folding kinetics of 52 representative proteins. Relative to the results from a common modeling approach, the diversity of the simulated folding rates can be increased from ~10(2.1) to the experimental ~10(6.0) by a modest decrease in the spatial range of the attractive potential. The required theoretical range is consistent with desolvation physics and is notably much more permissive than that needed for two-state-like homopolymer collapse. PMID- 24229310 TI - Self-propulsion in a low-Reynolds-number fluid confined by two walls of a microchannel. AB - The problem of hydrodynamic interactions with confining walls is examined for a model of a microswimmer composed of three connected beads. Two parallel walls of a narrow microfluidic channel confine the fluid flow. We show that different trajectories for this linear swimmer emerge because of long-range hydrodynamic interactions with the walls of the channel. The possibility of space-spanning trajectories for this swimmer can potentially introduce it as a candidate for constructing a mixing device for working at the laminar flow conditions in microfluidic channels. PMID- 24229311 TI - Quantum ion-acoustic solitary waves: the effect of exchange correlation. AB - Quantum ion-acoustic solitary waves are studied by considering the effects of exchange and correlation for the electrons. Starting from one-dimensional quantum hydrodynamic equations, including the term of exchange correlation for electrons, we obtain a model in which two dimensionless parameters appear (in addition to the parameter measuring the quantum diffraction) measuring the exchange and the correlation. A new deformed Korteweg-de Vries equation is derived. The effect of exchange and correlation is reflected in the phase speed as well as in the nonlinear and dispersion terms. Its solution shows that the exchange-correlation effects modify the amplitude as well as the width of the weak solitary waves. In the arbitrary amplitude regime, and as may be expected, a pseudopotential analysis shows that the exchange-correlation effects may change the nature (compressive or rarefactive) of the quantum ion-acoustic solitary waves. Our results complement and give new insight into the previously published work on this problem. PMID- 24229312 TI - Comment on "Stochastic dynamics of the prisoner's dilemma with cooperation facilitators". AB - In a recent paper [Phys. Rev. E 86, 011134 (2012)], Mobilia introduces cooperation facilitators in the standard prisoner's dilemma game. He claims that natural selection favors the replacement of defection by cooperation in the weak selection case if and only if their frequency satisfies a certain inequality. We show that this is not true, and we point out an error in the author's proof which follows from the improper handling of the large-population limit. In addition, we prove a stronger result that cooperation is favored for any selection strength if and only if the average payoff of cooperation is bigger than the average payoff of defection (which is a weaker condition than the author's inequality). We also show that, if we include self-interaction, then the presence of a fixed number of facilitators causes a rescaling of the payoff matrix, and for their certain frequency, cooperation becomes a dominant strategy, and the prisoner's dilemma simply disappears. PMID- 24229313 TI - Reply to "Comment on 'Stochastic dynamics of the prisoner's dilemma with cooperation facilitators' ". AB - The fixation properties of a simple prisoner's dilemma game in the presence of "cooperation facilitators" have recently been investigated in finite and well mixed populations for various dynamics [Mobilia, Phys. Rev. E 86, 011134 (2012)]. In a Comment, Miekisz claims that, for cooperation to be favored by selection in the standard prisoner's dilemma games with facilitators, it suffices that f(C)>f(D) (where f(C/D) are the respective fitnesses of cooperators and defectors). In this Reply, we show that, in generic prisoner's dilemma games with l cooperation facilitators, it is generally not sufficient that a single cooperator has a higher fitness than defectors to ensure that selection favors cooperation. In fact, it is also necessary that selection promotes the replacement of defection by cooperation in a population of size N, which requires that the fixation probability of a single cooperator exceeds (N-l)(-1). This replacement condition is independent of f(C)>f(D) and, when the payoff for mutual defection is negative, it is shown to be more stringent than the invasion condition. Our results, illustrated by a series of examples, considerably generalize those reported in the paper [Phys. Rev. E 86, 011134 (2012)] and in the aforementioned Comment whose claims are demonstrated to be relevant only for a special subclass of prisoner's dilemma games. PMID- 24229314 TI - Facile and sensitive method for detecting cardiac markers using ubiquitous pH meters. AB - A sensitive and easy method was developed for the detection of the cardiac marker troponin I using magnetic immunoassay and ubiquitous pH meters. Monoclonal antibody-functionalized Fe3O4 magnetic nanoparticle clusters (MNCs) were synthesized to capture troponin in human serum, and MNC-troponin complexes were magnetically isolated using a permanent magnet. These complexes were subsequently conjugated to polyclonal antibody-functionalized acetylcholinesterase (AchE) and dispersed in acetylcholine (Ach) solution. As the Ach was hydrolyzed to choline and acetic acid, the pH of the solution decreased, and the resulting pH change was measured in real time using a pH meter. The sensitivity of detection of this assay was found to be 10 pg/mL of troponin in human serum after 10 min of the hydrolysis reaction. Further, the pH change could be determined with the naked eye from the color change of a pH indicator strip. PMID- 24229316 TI - Decreasing frequency of office visits on fridays. AB - OBJECTIVES: To determine if the frequency of physician visits on Fridays varied over the course of 1997 to 2010, and if it varied by geographical region. METHODS: Data from the National Ambulatory Medical Care Survey (NAMCS) of the National Center for Health Statistics were analyzed to examine the frequency of office visits with physicians on Friday from 1997 to 2010, and the same data were also stratified by geographical location. RESULTS: Fewer office visits occurred on Fridays compared to other weekdays, and the percentage of total visits that occurred on Fridays decreased over time (p = 0.04). Comparing between the different geographical regions, the South had the lowest rate of Friday visits and the West had the highest rate. The Northeast (p = 0.003) and South (p < 0.0001) had significantly lower rates than the West. CONCLUSION: Although patients and physicians alike are disappointed in the amount of time physicians and patients spend face to face, physicians are currently not utilizing every day of the common workweek to see patients. PMID- 24229315 TI - How experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trials. AB - BACKGROUND: Accurately characterizing a drug's safety profile is essential. Trial harm and tolerability assessments rely, in part, on participants' reports of medical histories, adverse events (AEs), and concomitant medications. Optimal methods for questioning participants are unclear, but different methods giving different results can undermine meta-analyses. This study compared methods for eliciting such data and explored reasons for dissimilar participant responses. METHODS: Participants from open-label antimalarial and antiretroviral interaction trials in two distinct sites (South Africa, n = 18 [all HIV positive]; Tanzania, n = 80 [86% HIV positive]) were asked about ill health and treatment use by sequential use of (1) general enquiries without reference to particular conditions, body systems or treatments, (2) checklists of potential health issues and treatments, (3) in-depth interviews. Participants' experiences of illness and treatment and their reporting behaviour were explored qualitatively, as were trial clinicians' experiences with obtaining participant reports. Outcomes were the number and nature of data by questioning method, themes from qualitative analyses and a theoretical interpretation of participants' experiences. RESULTS: There was an overall cumulative increase in the number of reports from general enquiry through checklists to in-depth interview; in South Africa, an additional 12 medical histories, 21 AEs and 27 medications; in Tanzania an additional 260 medical histories, 1 AE and 11 medications. Checklists and interviews facilitated recognition of health issues and treatments, and consideration of what to report. Information was sometimes not reported because participants forgot, it was considered irrelevant or insignificant, or they feared reporting. Some medicine names were not known and answers to questions were considered inferior to blood tests for detecting ill health. South African inpatient volunteers exhibited a "trial citizenship", working to achieve researchers' goals, while Tanzanian outpatients sometimes deferred responsibility for identifying items to report to trial clinicians. CONCLUSIONS: Questioning methods and trial contexts influence the detection of adverse events, medical histories and concomitant medications. There should be further methodological work to investigate these influences and find appropriate questioning methods. PMID- 24229317 TI - Predicting physical activity in adolescents: the role of compensatory health beliefs within the Health Action Process Approach. AB - OBJECTIVE: Compensatory health beliefs (CHBs), defined as beliefs that healthy behaviours can compensate for unhealthy behaviours, may be one possible factor hindering people in adopting a healthier lifestyle. This study examined the contribution of CHBs to the prediction of adolescents' physical activity within the theoretical framework of the Health Action Process Approach (HAPA). DESIGN: The study followed a prospective survey design with assessments at baseline (T1) and two weeks later (T2). METHOD: Questionnaire data on physical activity, HAPA variables and CHBs were obtained twice from 430 adolescents of four different Swiss schools. Multilevel modelling was applied. RESULTS: CHBs added significantly to the prediction of intentions and change in intentions, in that higher CHBs were associated with lower intentions to be physically active at T2 and a reduction in intentions from T1 to T2. No effect of CHBs emerged for the prediction of self-reported levels of physical activity at T2 and change in physical activity from T1 to T2. CONCLUSION: Findings emphasise the relevance of examining CHBs in the context of an established health behaviour change model and suggest that CHBs are of particular importance in the process of intention formation. PMID- 24229318 TI - Japanese trends in breastfeeding rate in baby-friendly hospitals between 2007 and 2010: a retrospective hospital-based surveillance study. AB - BACKGROUND: The goal of Japan's national "Healthy and Happy Family 21" campaign is to increase the nationwide breastfeeding rate for babies in the first month of life, which is currently below 50%, to a level of 60%. In this article, we summarize the breastfeeding rate for all of Japan's baby-friendly hospitals (BFHs) and extract their strengths in conjunction with the structural and legislative support that they have in place and finally draw up a policy for dispersing BFH activities to non-BFH delivery facilities, which could be useful for increasing the breastfeeding rate. METHODS: This study included all of the 61 BFHs that are registered in Japan. These hospitals account for approximately 2% of nearly 3,000 Japanese delivery facilities. The surveillance data, which were collected anonymously by the Japan Breastfeeding Association in 2007-2010, were summarized. The numbers of babies who were breastfed after delivery, at discharge from BFHs and at one month of age, were collated. The length of hospital/clinic stay was also collected. RESULTS: The collection rate was 100% in each year (2007, 2008, 2009 and 2010). The breastfeeding rates during hospital stay, at discharge, and one month were >70%, ~90%, and >75%, respectively. The median length of stay was 5 days (minimum/maximum: 5/8) for primipara. CONCLUSIONS: The breastfeeding rate at BFHs at one month of age was more than 75%. This surpassed the current national average (<50%). The median length of hospital/clinic stay was 5 days. In this 5-day period, BFH activities can play an important role in increasing the breastfeeding rate. Since hospitalization for the reported national median length of stay of 6 days, is legally guaranteed, the disbursement of BFH activities to non-BFH delivery facilities, with special support to mothers who delivered by cesarean delivery, would be a useful strategy for achieving a 60% breastfeeding rate at one month of age. PMID- 24229320 TI - Consensus Definition of Nonallergic Rhinopathy, Previously Referred to as Vasomotor Rhinitis, Nonallergic Rhinitis, and/or Idiopathic Rhinitis. AB - "Nonallergic vasomotor rhinitis" (also referred to as nonallergic rhinitis and/or idiopathic rhinitis) is a term that has been used to describe a common nasal condition of unclear pathophysiology. The lack of straightforward diagnostic criteria is limiting; research for better treatment options requires the definition of homogeneous populations characterized by well-defined inclusion and exclusion criteria. Following considerable discussion and counterpoints at a roundtable conference convened in December 2008, we proposed to change the terminology to reference this condition as "nonallergic rhinopathy." Nonallergic rhinopathy is a chronic nasal condition with symptoms that may be perennial, persistent, intermittent, or seasonal and/or elicited by recognized triggers. There is a well-recognized set of clinical exposures that lead to the symptoms, predominantly congestion and rhinorrhea. The clinical characteristics as outlined provide well-defined inclusion and exclusion criteria that should permit precise identification of patients for participation in clinical trials. PMID- 24229319 TI - Isolation and characterization of a dihydroxo-bridged iron(III,III)(MU-OH)2 diamond core derived from dioxygen. AB - Dioxygen addition to coordinatively unsaturated [Fe(II)(O(Me2)N4(6-Me DPEN))](PF6) (1) is shown to afford a complex containing a dihydroxo-bridged Fe(III)2(MU-OH)2 diamond core, [Fe(III)(O(Me2)N4(6-Me-DPEN))]2(MU OH)2(PF6)2.(CH3CH2CN)2 (2). The diamond core of 2 resembles the oxidized methane monooxygenase (MMOox) resting state, as well as the active site product formed following H-atom abstraction from Tyr-OH by ribonucleotide reductase (RNR). The Fe-OH bond lengths of 2 are comparable with those of the MMOHox suggesting that MMOHox contains a Fe(III)2(MU-OH)2 as opposed to Fe(III)2(MU-OH)(MU-OH2) diamond core as had been suggested. Isotopic labeling experiments with (18)O2 and CD3CN indicate that the oxygen and proton of the MU-OH bridges of 2 are derived from dioxygen and acetonitrile. Deuterium incorporation (from CD3CN) suggests that an unobserved intermediate capable of abstracting a H-atom from CH3CN forms en route to 2. Given the high C-H bond dissociation energy (BDE = 97 kcal/mol) of acetonitrile, this indicates that this intermediate is a potent oxidant, possibly a high-valent iron oxo. Consistent with this, iodosylbenzene (PhIO) also reacts with 1 in CD3CN to afford the deuterated Fe(III)2(MU-OD)2 derivative of 2. Intermediates are not spectroscopically observed in either reaction (O2 and PhIO) even at low-temperatures (-80 degrees C), indicating that this intermediate has a very short lifetime, likely due to its highly reactive nature. Hydroxo-bridged 2 was found to stoichiometrically abstract hydrogen atoms from 9,10 dihydroanthracene (C-H BDE = 76 kcal/mol) at ambient temperatures. PMID- 24229321 TI - A laboratory-scale pretreatment and hydrolysis assay for determination of reactivity in cellulosic biomass feedstocks. AB - BACKGROUND: The rapid determination of the release of structural sugars from biomass feedstocks is an important enabling technology for the development of cellulosic biofuels. An assay that is used to determine sugar release for large numbers of samples must be robust, rapid, and easy to perform, and must use modest amounts of the samples to be tested.In this work we present a laboratory scale combined pretreatment and saccharification assay that can be used as a biomass feedstock screening tool. The assay uses a commercially available automated solvent extraction system for pretreatment followed by a small-scale enzymatic hydrolysis step. The assay allows multiple samples to be screened simultaneously, and uses only ~3 g of biomass per sample. If the composition of the biomass sample is known, the results of the assay can be expressed as reactivity (fraction of structural carbohydrate present in the biomass sample released as monomeric sugars). RESULTS: We first present pretreatment and enzymatic hydrolysis experiments on a set of representative biomass feedstock samples (corn stover, poplar, sorghum, switchgrass) in order to put the assay in context, and then show the results of the assay applied to approximately 150 different feedstock samples covering 5 different materials. From the compositional analysis data we identify a positive correlation between lignin and structural carbohydrates, and from the reactivity data we identify a negative correlation between both carbohydrate and lignin content and total reactivity. The negative correlation between lignin content and total reactivity suggests that lignin may interfere with sugar release, or that more mature samples (with higher structural sugars) may have more recalcitrant lignin. CONCLUSIONS: The assay presented in this work provides a robust and straightforward method to measure the sugar release after pretreatment and saccharification that can be used as a biomass feedstock screening tool. We demonstrated the utility of the assay by identifying correlations between feedstock composition and reactivity in a population of 150 samples. PMID- 24229322 TI - Adhesion G-protein-coupled receptors: elusive hybrids come of age. AB - Adhesion G-protein-coupled receptors (GPCRs) are the most recently identified and least understood subfamily of GPCRs. Adhesion GPCRs are characterized by unusually long ectodomains with adhesion-related repeats that facilitate cell- cell and cell-cell matrix contact, as well as a proteolytic cleavage site containing domain that is a structural hallmark of the family. Their unusual chimeric structure of adhesion-related ectodomain with a seven-pass transmembrane domain and cytoplasmic signaling makes these proteins highly versatile in mediating cellular signaling in response to extracellular adhesion or cell motility events. The ligand binding and cytoplasmic signaling modes for members of this family are beginning to be elucidated, and recent studies have demonstrated critical roles for Adhesion GPCRs in planar polarity and other important cell-cell and cell-matrix interactions during development and morphogenesis, as well as heritable diseases and cancer. PMID- 24229323 TI - Speckle tracking derived strain in infants with severe perinatal asphyxia: a comparative case control study. AB - BACKGROUND: Speckle tracking echocardiography is increasingly being used to assess cardiac function in neonates. The objective was to compare speckle tracking strain indices between asphyxiated infants and healthy controls and to ascertain correlations between strain and 2D Doppler derived indices and cardiac troponin (biochemical marker of myocardial injury). METHODS: Clinical and echocardiographic data from severely asphyxiated infants undergoing therapeutic hypothermia was evaluated retrospectively. This was compared with prospective data from healthy infants. Correlations between variables were assessed using Pearson's coefficient of correlation. RESULTS: Twenty four infants with severe perinatal asphyxia were admitted during the study period of which 3 were not cooled and were excluded. The gestational age and birth weights of cases and controls were comparable. The mean left ventricular global longitudinal strain (GLS) from apical 4 chamber view was noted to be significantly impaired in the asphyxiated infants (- 11.01% +/- 2.48 vs - 21.45% +/- 2.74, p <0.001). Cardiac output was significantly lower in the asphyxiated infants (97 +/- 26 vs 230 +/- 60 ml/kg/min). In asphyxiated infants, GLS correlated positively with cardiac output (r2 = 0.86, p< 0.001) and negatively with serum troponin levels (r2 = 0.64, p< 0.001). GLS was less impaired in infants on inotropes compared to those not on inotropic support, -12.55% (1.9) vs -10.2% (1.3), p= 0.018. Infants who died had a lower global strain value compared to survivors, - 9.7% (1.6) vs - 12.8% (2.6), p = 0.02. CONCLUSIONS: 2D Speckle derived strain was impaired in asphyxiated infants. Significant correlations between GLS and cardiac output and troponin were noted. PMID- 24229325 TI - Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-hydroxy-2-nonenal. AB - Oxidative stress has been implicated as a component of various pathologies including ischemia/reperfusion injury (IRI) and neurodegenerative diseases such as Parkinson's disease (PD) and schizophrenia. Similarly, regulator of G-protein signaling 4 (RGS4) has been implicated as an important player in each of these pathologies. RGS4, like other RGS proteins, is responsible for temporally regulating G-protein coupled receptor signaling by increasing the intrinsic GTPase activity of Galpha subunit of the heterotrimeric signaling complex. In this study we evaluated whether modification by 4-hydroxy-2-nonenal (4HNE), a common lipid peroxidation product, inhibits RGS4. Using immunoprecipitation, we first determined RGS4 modification was occurring in cells at concentrations of 4HNE within reported physiological conditions. Following this determination, we evaluated modification of RGS4 by 4HNE by both Western blot and mass spectrometry (MS). Once it was established that covalent modification occurred only on cysteine containing constructs, tryptic digest followed by mass spectrometry analysis revealed modification occurs at cysteine residues 71, 148, and 183. In order to determine the effect 4HNE had on RGS4 activity, a steady-state colorimetric assay was used to analyze the GAP activity of Delta51-RGS4 as well as the cysteine null mutant. From the data, we determined that RGS4 activity can be modulated by 4HNE through modification at cysteine residues similar to previously reported small molecule inhibition of RGS4. PMID- 24229327 TI - Retraction: Enhanced resistive switching memory characteristics and mechanism using a Ti nanolayer at the W/TaOx interface. PMID- 24229329 TI - Preparation of silicon@silicon oxide core-shell nanowires from a silica precursor toward a high energy density Li-ion battery anode. AB - Bulk-quantity silicon@silicon oxide nanowires have been successfully synthesized via a facile high-temperature approach using environment-friendly silica mixed with titanium powders. It is confirmed that the obtained nanowires process a crystalline core and amorphous oxide sheath. The obtained nanowires grow along the [111] direction which catalyzed by spherical silicon@siilcon oxide nanoparticles. The unique one-dimensional structure and thin oxide sheath result in the favorable electrochemical performances, which may be beneficial to the high energy density silicon anode for lithium ion batteries. PMID- 24229334 TI - Putting people first: re-thinking the role of technology in augmentative and alternative communication intervention. AB - Current technologies provide individuals with complex communication needs with a powerful array of communication, information, organization, and social networking options. However, there is the danger that the excitement over these new devices will result in a misplaced focus on the technology, to the neglect of what must be the central focus - the people with complex communication needs who require augmentative and alternative communication (AAC). In order to truly harness the power of technology, rehabilitation and educational professionals must ensure that AAC intervention is driven, not by the devices, but rather by the communication needs of the individual. Furthermore, those involved in AAC research and development activities must ensure that the design of AAC technologies is driven by an understanding of motor, sensory, cognitive, and linguistic processing, in order to minimize learning demands and maximize communication power for individuals with complex communication needs across the life span. PMID- 24229333 TI - The Academic Backbone: longitudinal continuities in educational achievement from secondary school and medical school to MRCP(UK) and the specialist register in UK medical students and doctors. AB - BACKGROUND: Selection of medical students in the UK is still largely based on prior academic achievement, although doubts have been expressed as to whether performance in earlier life is predictive of outcomes later in medical school or post-graduate education. This study analyses data from five longitudinal studies of UK medical students and doctors from the early 1970s until the early 2000s. Two of the studies used the AH5, a group test of general intelligence (that is, intellectual aptitude). Sex and ethnic differences were also analyzed in light of the changing demographics of medical students over the past decades. METHODS: Data from five cohort studies were available: the Westminster Study (began clinical studies from 1975 to 1982), the 1980, 1985, and 1990 cohort studies (entered medical school in 1981, 1986, and 1991), and the University College London Medical School (UCLMS) Cohort Study (entered clinical studies in 2005 and 2006). Different studies had different outcome measures, but most had performance on basic medical sciences and clinical examinations at medical school, performance in Membership of the Royal Colleges of Physicians (MRCP(UK)) examinations, and being on the General Medical Council Specialist Register. RESULTS: Correlation matrices and path analyses are presented. There were robust correlations across different years at medical school, and medical school performance also predicted MRCP(UK) performance and being on the GMC Specialist Register. A-levels correlated somewhat less with undergraduate and post-graduate performance, but there was restriction of range in entrants. General Certificate of Secondary Education (GCSE)/O-level results also predicted undergraduate and post-graduate outcomes, but less so than did A-level results, but there may be incremental validity for clinical and post-graduate performance. The AH5 had some significant correlations with outcome, but they were inconsistent. Sex and ethnicity also had predictive effects on measures of educational attainment, undergraduate, and post-graduate performance. Women performed better in assessments but were less likely to be on the Specialist Register. Non-white participants generally underperformed in undergraduate and post-graduate assessments, but were equally likely to be on the Specialist Register. There was a suggestion of smaller ethnicity effects in earlier studies. CONCLUSIONS: The existence of the Academic Backbone concept is strongly supported, with attainment at secondary school predicting performance in undergraduate and post-graduate medical assessments, and the effects spanning many years. The Academic Backbone is conceptualized in terms of the development of more sophisticated underlying structures of knowledge ('cognitive capital' and 'medical capital'). The Academic Backbone provides strong support for using measures of educational attainment, particularly A-levels, in student selection. PMID- 24229335 TI - Communication support through multimodal supplementation: a scoping review. AB - Speech supplementation strategies improve spoken communication for people with motor speech disorders who experience reduced speech intelligibility. The purpose of this review was to summarize the literature on traditional supplementation strategies (e.g., alphabet supplementation, topic supplementation, and gestural supplementation) and to expand the definition of speech supplementation to include additional modalities, such as augmenting speech with pictures via mobile technology, and conversation management strategies. Results showed that studies of traditional supplementation consistently reported positive outcomes, including increased intelligibility, decreased speech rate, and positive attitudes toward speakers. New modalities, such as supplementing speech through digital photos, may come to be integrated with traditional approaches, given the proliferation of digital photography and mobile tablet technologies. In addition, new research is exploring the role of communication partners in dyads where one speaker has dysarthria, as well as strategies that communication partners employ to understand dysarthric speech. PMID- 24229336 TI - Teaching conceptually referenced core vocabulary for initial augmentative and alternative communication. AB - Individuals with significant intellectual disabilities who use augmentative and alternative communication (AAC) often fail to acquire large vocabularies. To maximize the functionality of a small vocabulary, AAC users' initial vocabulary typically consists of words that can be used frequently across contexts and functions (i.e., core vocabulary). For many AAC users, core vocabulary often references concepts rather than concrete items. For individuals with severe intellectual disabilities, however, initial AAC vocabulary often consists of concretely referenced words instead. There is little evidence that these individuals can learn to use conceptually referenced words in initial AAC. A variation of a single subject multiple baseline design across four stimuli was used to demonstrate that an individual with severe intellectual disabilities could learn to use conceptually referenced words as an initial AAC vocabulary. As a result of the intervention (a modified PECS procedure), a 9-year-old boy with multiple disabilities, including intellectual disability and deaf-blindness, learned to make appropriate use of three conceptually referenced tactile symbols for the concepts of more, done, and new as an initial communication vocabulary. PMID- 24229326 TI - Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. AB - BACKGROUND: 'Encephalomyelitis disseminata' (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS. DISCUSSION: There are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels. SUMMARY: This review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to develop symptoms of ME/CFS. PMID- 24229338 TI - Exploring the impact of cognition on young children's ability to navigate a speech-generating device. AB - This study examined the impact of cognition on young children's ability to navigate a speech-generating device (SGD) with dynamic paging. Knowledge of which cognitive factors impact navigational skills could help clinicians select the most appropriate SGD for children who have complex communication needs. A total of 65 typically developing children aged 48-77 months were assessed using the Leiter International Performance Scale-Revised (Leiter-R) and the Automated Working Memory Assessment (AWMA). Although significant correlations were found between the ability to navigate an SGD (using a taxonomic organization) and all cognitive factors except for cognitive flexibility, a stepwise linear regression revealed that sustained attention, categorization, and fluid reasoning were the most pragmatic set of factors to predict navigational skills. Future studies are needed to further understand the factors that impact children's navigational skills. PMID- 24229337 TI - Support for AAC use in preschool, and growth in language skills, for young children with developmental disabilities. AB - Little is known about how AAC use in preschool may impact language development for children with complex communication needs (e.g., children with autism, cerebral palsy, Down syndrome, and other developmental disabilities). We developed two surveys (a) to describe children's use of AAC in preschool classrooms, as well as the use of prompts and question asking, and augmented input by their communication partners; and (b) to describe teachers' experience, training, and perceived support in providing AAC. We then examined the relationship between children's experience of AAC, including the use of prompts, question asking, and augmented input by their partners, and the growth of receptive and expressive language for 71 children with developmental disabilities over a two-year period. The use of AAC by peers to provide augmented input was associated with stronger language growth; the use of prompting and question asking by teachers was associated with weaker language growth. Teachers reported that they received little training regarding ways to support a child's use of AAC. Results suggest the need for further research on promoting AAC use at the preschool level, including research to promote peer interactions for AAC users. PMID- 24229339 TI - The iconicity of picture communication symbols for children with English additional language and mild intellectual disability. AB - The purpose of this study was to examine the iconicity of 16 Picture Communication Symbols (PCS) presented on a themed bed-making communication overlay for South African children with English as an additional language and mild intellectual disability. The survey involved 30 participants. The results indicated that, overall, the 16 symbols were relatively iconic to the participants. The authors suggest that the iconicity of picture symbols could be manipulated, enhanced, and influenced by contextual effects (other PCS used simultaneously on the communication overlay). In addition, selection of non target PCS for target PCS were discussed in terms of postulated differences in terms of distinctiveness. Potential clinical implications and limitations of the study, as well as recommendations for future research, are discussed. PMID- 24229340 TI - Consensus Review and Definition of Nonallergic Rhinitis With a Focus on Vasomotor Rhinitis, Proposed to be Known henceforth as Nonallergic Rhinopathy Part 1. Introduction. AB - "Nonallergic vasomotor rhinitis" (also referred to as nonallergic rhinitis and/or idiopathic rhinitis) is a term that has been used to describe a common nasal condition of unclear pathophysiology. Clinical options for patients are limited by a lack of straightforward diagnostic criteria and poorly defined and heterogeneous populations in clinical trials. A roundtable conference convened in December 2008 addressed these challenges. The outcomes were (1) a revised clinical definition and (2) appropriate inclusion and exclusion criteria (based on the revised definition) to be used for the enrollment of subjects in future clinical studies. PMID- 24229341 TI - Improving physical activity in COPD: towards a new paradigm. AB - Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally. Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD. Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all cause mortality. Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes. In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels. To date, only limited evidence exists to support the effectiveness of these interventions. We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. PMID- 24229342 TI - Differences in the perceived role of the healthcare provider in delivering vascular health checks: a Q methodology study. AB - BACKGROUND: The UK Department of Health introduced the National Health Service (NHS) Health Check Programme in April 2009 in an attempt to improve primary and secondary prevention of cardiovascular disease in the UK population and to reduce health inequalities. Healthcare professionals' attitudes towards giving lifestyle advice will influence how they interact with patients during consultations. We therefore sought to identify the attitudes of primary care healthcare professionals towards the delivery of lifestyle advice in the context of the NHS Health Check Programme. METHODS: Fifty-two primary care healthcare professionals undertook a Q sort with 36 statements that represented a range of viewpoints about the importance of lifestyle change, medication, giving lifestyle advice in the primary care setting, and the individual, social and material factors that might impact on lifestyle related behaviour change. Sorts were analysed by-person using principal components analysis and varimax rotation. RESULTS: Five statistically independent factors (accounts) reflected distinct views on the topic. Account 1 was supportive of initiatives like the NHS Health Check, and emphasised the importance of professionals working collaboratively with patients to facilitate lifestyle change. Account 2 expressed views on the potential overuse of statin medication and placed responsibility for lifestyle change with the patient. Account 3 viewed the healthcare professional role to be one of educator, emphasising the provision of information. Account 4 perceived lifestyle change to be difficult for patients and emphasised the need for healthcare professionals to be role models. Account 5 was inconsistent about the value of lifestyle change, or the role of healthcare professionals in promoting it, a finding that may be due to ambivalence about the health check or to lack of engagement with the Q sort task. We found no strong associations between any of the factors and, gender, role, age or ethnicity. CONCLUSIONS: Our findings suggest that healthcare professionals hold viewpoints that may influence how they interact with patients during health checks. When implementing programmes like the NHS Health Check, it would be useful to take healthcare professionals' views into account. Attitudes and beliefs could be explored during training sessions, for example. PMID- 24229343 TI - The challenges of implementing a telestroke network: a systematic review and case study. AB - BACKGROUND: The use of telemedicine in acute stroke care can facilitate rapid access to treatment, but the work required to embed any new technology into routine practice is often hidden, and can be challenging. We aimed to collate recommendations and resources to support telestroke implementation. METHODS: Systematic search of healthcare databases and the Internet to identify descriptions of the implementation of telestroke projects; interviews with key stakeholders during the development of one UK telestroke network. Supporting documentation from existing projects was analysed to construct a framework of implementation stages and tasks, and a toolkit of documents. Interviews and literature were analysed with other data sources using Normalisation Process Theory as described in the e-Health Implementation Toolkit. RESULTS: 61 telestroke projects were identified and contacted. Twenty projects provided documents, 13 with published research detailing four stages of telestroke system development, implementation, use, and evaluation. Interviewees identified four main challenges: engaging and maintaining the commitment of a wide range of stakeholders across multiple organisations; addressing clinicians perceptions of evidence, workload, and payback; managing clinical and technical workability across diverse settings; and monitoring how the system is used and reconfigured by users. CONCLUSIONS: Information to guide telestroke implementation is sparse, but available. By using multiple sources of data, sufficient information was collated to construct a web-based toolkit detailing implementation tasks, resources and challenges in the development of a telestroke system for assessment and thrombolysis delivery in acute care. The toolkit is freely available online. PMID- 24229344 TI - Differences of left ventricular systolic deformation in hypertensive patients with and without apical hypertrophic cardiomyopathy. AB - BACKGROUND: We tested the hypothesis that the apical myocardial mechanics differ from those of other ventricular segments in hypertensive patients with and without apical hypertrophic cardiomyopathy (ApHCM). METHODS: We retrospectively studied hypertensive patients with and without ApHCM. Left ventricular longitudinal, circumferential, and radial strains were examined by two dimensional speckle-tracking echocardiography at the basal, middle, and apical walls of the parasternal short-axis and apical 2-, 3- and 4-chamber views. RESULTS: Fourteen consecutive patients with hypertension and ApHCM and 14 patients with hypertension without ApHCM were studied. Lower mitral annular peak systolic velocity and greater diastolic dysfunction were present in hypertensive patients with ApHCM than in hypertensive patients without ApHCM. Compared with hypertensive patients without ApHCM, hypertensive patients with ApHCM had significantly lower apical longitudinal (-13.9% vs -21.9%, p = 0.010) and radial strains (4.4% vs 11.5%, p = 0.017) without the base-to-apex gradient. The global longitudinal (-15.6% vs -18.8%, p = 0.027) and circumferential strains (-16.1% vs -19.2%, p = 0.019) were significantly lower in hypertensive patients with ApHCM than in hypertensive patients without ApHCM. Among systolic parameters, the global longitudinal strain was independently associated with hypertension with ApHCM (odds ratio, 1.457; 95% confidence interval, 1.002-2.119; p = 0.049). CONCLUSIONS: Reduced apical longitudinal and radial strains without a base-to apex gradient were present in hypertensive patients with ApHCM. The global longitudinal strain was independently associated with ApHCM in hypertensive patients. PMID- 24229345 TI - Study of long-acting reversible contraceptive use in a UK primary care database: validation of methodology. AB - OBJECTIVES To develop and validate algorithms to identify new users of long acting reversible contraceptives (LARCs) in a primary care database, The Health Improvement Network (THIN). METHODS Women in THIN aged 12 to 49 years in 2005 were studied. THIN was searched using Read and MULTILEX codes to identify new users of copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and progestogen-only implants. Validation was undertaken for a randomly selected sample of 398 LARC users, in which their primary care physicians were asked to complete a questionnaire detailing LARC use. RESULTS Questionnaires were received for 379 patients (95%), confirming 316 (83%) as new LARC users. Confirmation rates for Cu-IUDs, the LNG-IUS and progestogen-only implants were 64%, 94% and 89%, respectively. The use of Read codes alone had the lowest confirmation rate, particularly for Cu-IUD users. Confirmation rates increased by using MULTILEX codes when available, or by examination of computerised medical records. CONCLUSIONS Computer algorithms were used to identify new LARC users. While THIN is a useful resource for studying LARC uptake, steps to gather additional information are necessary to ensure the validity of LARC classification. PMID- 24229346 TI - A program of positive intervention in the elderly: memories, gratitude and forgiveness. AB - OBJECTIVE: The main goal of this study has been to increase the quality of life in people of over 60 years through a positive psychology intervention. METHOD: We employed a program which consists of training based on autobiographical memory, forgiveness and gratitude. The sample consisted of 46 participants aged 60-93 years. State and trait anxiety, depression, general memory, specific memories, life satisfaction and subjective happiness were measured. RESULTS: The results revealed that participants who followed the program (experimental group) showed a significant decrease in state anxiety and depression as well as an increase in specific memories, life satisfaction and subjective happiness, compared with the placebo group. CONCLUSION: Our program offers promising results and provides new evidence for the effectiveness of positive interventions in the field of psychogerontology, helping increase subjective well-being and quality of life in older adults by focusing interventions on the enhancement of personal and social resources for being happy. PMID- 24229348 TI - Orbital localization criterion as a complementary tool in the bonding analysis by means of electron localization function: study of the Si(n)(BH)(5-n)(2-) (n = 0 5) clusters. AB - A recently proposed molecular orbital localization procedure, based on the electron localization function (ELF) technique, has been used to describe chemical bonding in the cluster series Sin(BH)(5-n)(2-) (n = 0-5). The method combines the chemically intuitive information obtained from the traditional ELF analysis with the flexibility and generality of canonical molecular orbital theory. This procedure attempts to localize the molecular orbitals in regions that have the highest probability for finding a pair of electrons, providing a chemical bonding description according to the classical Lewis theory. The results confirm that conservation of the structures upon isoelectronic replacement of a B H group by a Si atom, allowing evolution from B5H5(2-) to Si5(2-), is in total agreement with the preservation of the chemical bonding pattern. PMID- 24229347 TI - NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases. AB - BACKGROUND: Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons in the human brain. Although the majority of NDs are sporadic, evidence is accumulating that they have a strong genetic component. Therefore, significant efforts have been made in recent years to not only identify disease causing genes but also genes that modify the severity of NDs, so-called genetic modifiers. To date there exists no compendium that lists and cross-links genetic modifiers of different NDs. DESCRIPTION: In order to address this need, we present NeuroGeM, the first comprehensive knowledgebase providing integrated information on genetic modifiers of nine different NDs in the model organisms D. melanogaster, C. elegans, and S. cerevisiae. NeuroGeM cross-links curated genetic modifier information from the different NDs and provides details on experimental conditions used for modifier identification, functional annotations, links to homologous proteins and color-coded protein-protein interaction networks to visualize modifier interactions. We demonstrate how this database can be used to generate new understanding through meta-analysis. For instance, we reveal that the Drosophila genes DnaJ-1, thread, Atx2, and mub are generic modifiers that affect multiple if not all NDs. CONCLUSION: As the first compendium of genetic modifiers, NeuroGeM will assist experimental and computational scientists in their search for the pathophysiological mechanisms underlying NDs. http://chibi.ubc.ca/neurogem. PMID- 24229350 TI - Area selective molecular layer deposition of polyurea films. AB - Patterned organic thin films with submicrometer features are of great importance in applications such as nanoelectronics and optoelectronics. We present here a new approach for creating patterned organic films using area selective molecular layer deposition (MLD). MLD is a technique that allows for conformal deposition of nanoscale organic thin films with exceptional control over vertical thickness and composition. By expanding the technique to allow for area selective MLD, lateral patterning of the film can be achieved. In this work, polyurea thin films were deposited by alternating pulses of 1,4-phenylenediisocyanate (PDIC) and ethylenediamine (ED) in a layer-by-layer fashion with a linear growth rate of 5.3 A/cycle. Studies were carried out to determine whether self-assembled monolayer (SAM) formed from octadecyltrichlorosilane (ODTS) could block MLD on silicon substrates. Results show that the MLD process is impeded by the SAM. To test lateral patterning in MLD, SAMs were patterned onto silicon substrates using two different approaches. In one approach, SiO2-coated Si(100) substrates were patterned with an ODTS SAM by soft lithography in a well-controlled environment. In the second approach, patterned ODTS SAM was formed on H-Si/SiO2 patterned wafers by employing the chemically selective adsorption of ODTS on SiO2 over H Si. Auger electron spectroscopy results revealed that the polyurea film is deposited predominantly on the ODTS-free regions of both patterned substrates, indicating sufficient blocking of MLD by the ODTS SAM layer to replicate the pattern. The method we describe here offers a novel approach for fabricating high quality, three-dimensional organic structures. PMID- 24229349 TI - Mediterranean dietary pattern and depression: the PREDIMED randomized trial. AB - BACKGROUND: A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. METHODS: This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevencion con Dieta Mediterranea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression. RESULTS: We identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98). CONCLUSIONS: The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2. TRIAL REGISTRATION: This trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639. PMID- 24229351 TI - Effects of cobalt precursor on pyrolyzed carbon-supported cobalt-polypyrrole as electrocatalyst toward oxygen reduction reaction. AB - A series of non-precious metal electrocatalysts, namely pyrolyzed carbon supported cobalt-polypyrrole, Co-PPy-TsOH/C, are synthesized with various cobalt precursors, including cobalt acetate, cobalt nitrate, cobalt oxalate, and cobalt chloride. The catalytic performance towards oxygen reduction reaction (ORR) is comparatively investigated with electrochemical techniques of cyclic voltammogram, rotating disk electrode and rotating ring-disk electrode. The results are analyzed and discussed employing physiochemical techniques of X-ray diffraction, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, elemental analysis, and extended X-ray absorption fine structure. It shows that the cobalt precursor plays an essential role on the synthesis process as well as microstructure and performance of the Co-PPy-TsOH/C catalysts towards ORR. Among the studied Co-PPy TsOH/C catalysts, that prepared with cobalt acetate exhibits the best ORR performance. The crystallite/particle size of cobalt and its distribution as well as the graphitization degree of carbon in the catalyst greatly affects the catalytic performance of Co-PPy-TsOH/C towards ORR. Metallic cobalt is the main component in the active site in Co-PPy-TsOH/C for catalyzing ORR, but some other elements such as nitrogen are probably involved, too. PMID- 24229353 TI - Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies. AB - BACKGROUND: Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. METHODS: Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. RESULTS: Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. CONCLUSIONS: Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, 'dark matter' and 'dark energy' are posited to balance various theoretical equations, so medical student selection must also have its 'dark variance', whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills. PMID- 24229355 TI - Construct validity and temporal stability of the abridged 31-item Illness Behaviour Questionnaire. AB - OBJECTIVE: Key psychometric information was sought for three newly derived dimensions from an abridged Illness Behaviour Questionnaire (IBQ-31): Affirmation of Illness (AI), Concern for Health (CH) and General Affective State (GAS). The construct validity of these scales was examined along with their test-retest reliability and long-term stability. DESIGN: A longitudinal, observational study was conducted with 675 participants (general community members and those with either asthma, diabetes and chronic pain or chronic fatigue syndrome) providing self-report questionnaire data at baseline, with additional information sought at three (n = 483; 71.6%) and 12 months (n = 517, 76.6%). MAIN OUTCOME MEASURES: Construct validity of the IBQ-31 was explored using well-validated psychological measures of Symptom Attributions and Symptom Experience, Cognitive Distortion of Somatic Information and Illness Likelihood. RESULTS: In general, AI, CH and GAS shared predictable empirical overlap with related psychological indices across the five samples. Adequate three-month test-retest reliability was evident, with greater score variability over 12 months. CONCLUSION: The IBQ-31 comprises three theoretically relevant dimensions which demonstrate relative short- and long-term stability for individuals with diverse illness experiences. Future investigations should explore the predictive validity of AI, CH and GAS, along with the potential value of 'cut-off' scores for clinical use. PMID- 24229356 TI - High-content assays for hepatotoxicity using induced pluripotent stem cell derived cells. AB - Development of predictive in vitro assays for early toxicity evaluation is extremely important for improving the drug development process and reducing drug attrition rates during clinical development. High-content imaging-based in vitro toxicity assays are emerging as efficient tools for safety and efficacy testing to improve drug development efficiency. In this report we have used an induced pluripotent stem cell (iPSC)-derived hepatocyte cell model having a primary tissue-like phenotype, unlimited availability, and the potential to compare cells from different individuals. We examined a number of assays and phenotypic markers and developed automated screening methods for assessing multiparameter readouts of general and mechanism-specific hepatotoxicity. Endpoints assessed were cell viability, nuclear shape, average and integrated cell area, mitochondrial membrane potential, phospholipid accumulation, cytoskeleton integrity, and apoptosis. We assayed compounds with known mechanisms of toxicity and also evaluated a diverse hepatotoxicity library of 240 compounds. We conclude that high-content automated screening assays using iPSC-derived hepatocytes are feasible, provide information about mechanisms of toxicity, and can facilitate the safety assessment of drugs and chemicals. PMID- 24229358 TI - German database on the occurrence of food additives: application for intake estimation of five food colours for toddlers and children. AB - To get a more realistic estimation of food additive intake for toddlers and children, a German database on the occurrence of food additives was created. It uses consumption data of two recent national nutrition surveys for toddlers and children in combination with qualitative information of food additive occurrence in the consumed food. The information on food additive occurrence is based on food labelling. A categorisation system was developed according to regulations to classify the foods consumed and to identify possible food additive use in the food groups. Two natural (E120, E160b) and three artificial food colours (E110, E124, E129) were chosen for an assessment of food additive intake. The percentage of food items containing one of the chosen food colours was calculated for every food group and the food groups with most items containing the additive were identified. Intake estimations were performed based on maximum permitted-use levels (MPLs). Firstly, additive use was assumed in all foods consumed (tier 2); and secondly, food additive use was assumed only for those items where labelling confirmed the use and for all foods with no labelling available (tier 2b). Intake estimations were then compared with the ADI. Most food items with at least one of the food colours were found in the food groups confectionary, desserts, fermented milk products, flavoured drinks and breakfast cereals. The tier 2b approach provided more realistic estimations, which were always below those of the tier 2 approach and below the ADI for mean exposure. Exposure for high-level consumers exceeded the ADI for two of the food additives in tier 2b. Keeping in mind that the database is only mirroring the current situation, it provides a good possibility to refine the estimation of food additive intake for toddlers and children in Germany. PMID- 24229357 TI - A fluorescence anisotropy-based Myt1 kinase binding assay. AB - Abstract The human Myt1 kinase is a regulator of Cdk1/CycB and, hence, important for the G2/M transition in the cell cycle. It may act as a target for drug development, but suitable assay systems for assessing potential inhibitors are lacking so far. Herein, we describe the rational development of a fluorescence anisotropy-based kinase binding assay. A suitable fluoroprobe based on the tyrosine kinase inhibitor dasatinib was synthesized and tested with Myt1 and several other kinases for control purposes. The probe acted as expected in terms of specificity and reversibility, and a Myt1 assay was set up. Notwithstanding the moderate Kd of the starting compound dasatinib before chemical modification, satisfying Z' factors >0.5 were achieved. A validation with known kinase inhibitors demonstrated the applicability of the assay and led to a reliable ranking of the tested active compounds. PMID- 24229359 TI - Essential roles of nucleotide-switch and metal-coordinating residues for chaperone function of diol dehydratase-reactivase. AB - Diol dehydratase-reactivase (DD-R) is a molecular chaperone that reactivates inactivated holodiol dehydratase (DD) by cofactor exchange. Its ADP-bound and ATP bound forms are high-affinity and low-affinity forms for DD, respectively. Among DD-Rs mutated at the nucleotide-binding site, neither the Dalpha8N nor Dalpha413N mutant was effective as a reactivase. Although Dalpha413N showed ATPase activity, it did not mediate cyanocobalamin (CN-Cbl) release from the DD.CN-Cbl complex in the presence of ATP or ADP and formed a tight complex with apoDD even in the presence of ATP, suggesting the involvement of Aspalpha413 in the nucleotide switch. In contrast, Dalpha8N showed very low ATPase activity and did not mediate CN-Cbl release from the complex in the presence of ATP, but it did cause about 50% release in the presence of ADP. The complex formation of this mutant with DD was partially reversed by ATP, suggesting that Aspalpha8 is involved in the ATPase activity but only partially in the nucleotide switch. Among DD-Rs mutated at the Mg(2+)-binding site, only Ebeta31Q was about 30% as active as wild-type DD R and formed a tight complex with apoDD, indicating that the DD-R beta subunit is not absolutely required for reactivation. If subunit swapping occurs between the DD-R beta and DD beta subunits, Glubeta97 of DD would coordinate to Mg(2+). The complex of Ebeta97Q DD with CN-Cbl was not activated by wild-type DD-R. No complex was formed between this mutant and wild-type DD-R, indicating that the coordination of Glubeta97 to Mg(2+) is essential for subunit swapping and therefore for (re)activation. PMID- 24229360 TI - Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomised controlled trial. AB - BACKGROUND: Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough. METHODS: In this randomised controlled trial 84 patients met the eligibility criteria: age of >=40 years, COPD GOLD stage >=2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored. RESULTS: Mean age of participants was 68 +/- 10 years and mean FEV1 was 1.36 +/- 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 +/- 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non significant. No imbalances in adverse events were found. CONCLUSIONS: Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree. TRIAL REGISTRATION: ClinicalTrials.gov NCT01071161. PMID- 24229361 TI - Item selection, reliability and validity of the Shortness of Breath with Daily Activities (SOBDA) questionnaire: a new outcome measure for evaluating dyspnea in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow. Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients' daily activities. To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA). Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA. METHODS: Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States. The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary. Patients answered every item and rated their level of SOB experienced that day during specific activities. Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results. The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input. The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness. RESULTS: Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert's discretion. Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91. Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61). Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity. Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study. CONCLUSIONS: Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development. The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. PMID- 24229363 TI - Highly stable alkaline polymer electrolyte based on a poly(ether ether ketone) backbone. AB - Alkaline polymer electrolyte fuel cells (APEFCs) promise the use of nonprecious metal catalysts and thus have attracted much research attention in the recent decade. Among the challenges of developing practical APEFC technology, the chemical stability of alkaline polymer electrolytes (APEs) seems to be rather difficult. Research found that, upon attachment of a cationic functional group, an originally stable polymer backbone, such as polysulfone (PSF), would degrade in an alkaline environment. In the present work, we try to employ poly(ether ether ketone) (PEEK), a very inert engineering plastic, as the backbone of APEs. The PEEK is functionalized with both a sulfonic acid (SA) group and a quaternary ammonia (QA) group, with the latter as the majority amount. Ionic cross-linking between SA and QA has rendered the thus-obtained membrane (xQAPEEK) with high mechanical strength and low swelling degree. More importantly, the xQAPEEK membrane exhibits outstanding stability in a 1 mol/L KOH solution at 80 degrees C for a test period of 30 days: the total weight loss of xQAPEEK is only 6 wt %, in comparison to a large degradation of quaternary ammonia PSF (more than 40 wt %) under the same conditions. Our findings not only have demonstrated an effective approach to preparing PEEK-based APE but also cast a new light on the development of highly stable APEs for fuel-cell application. PMID- 24229362 TI - Study protocol: Rehabilitation including Social and Physical activity and Education in Children and Teenagers with Cancer (RESPECT). AB - BACKGROUND: During cancer treatment children have reduced contact with their social network of friends, and have limited participation in education, sports, and leisure activities. During and following cancer treatment, children describe school related problems, reduced physical fitness, and problems related to interaction with peers. METHODS/DESIGN: The RESPECT study is a nationwide population-based prospective, controlled, mixed-methods intervention study looking at children aged 6-18 years newly diagnosed with cancer in eastern Denmark (n=120) and a matched control group in western Denmark (n=120). RESPECT includes Danish-speaking children diagnosed with cancer and treated at pediatric oncology units in Denmark. Primary endpoints are the level of educational achievement one year after the cessation of first-line cancer therapy, and the value of VO2max one year after the cessation of first-line cancer therapy. Secondary endpoints are quality of life measured by validated questionnaires and interviews, and physical performance. RESPECT includes a multimodal intervention program, including ambassador-facilitated educational, physical, and social interventions. The educational intervention includes an educational program aimed at the child with cancer, the child's schoolteachers and classmates, and the child's parents. Children with cancer will each have two ambassadors assigned from their class. The ambassadors visit the child with cancer at the hospital at alternating 2-week intervals and participate in the intervention program. The physical and social intervention examines the effect of early, structured, individualized, and continuous physical activity from diagnosis throughout the treatment period. The patients are tested at diagnosis, at 3 and 6 months after diagnosis, and one year after the cessation of treatment. The study is powered to quantify the impact of the combined educational, physical, and social intervention programs. DISCUSSION: RESPECT is the first population-based study to examine the effect of early rehabilitation for children with cancer, and to use healthy classmates as ambassadors to facilitate the normalization of social life in the hospital. For children with cancer, RESPECT contributes to expanding knowledge on rehabilitation that can also facilitate rehabilitation of other children undergoing hospitalization for long-term illness. TRIAL REGISTRATION: Clinical Trials.gov: file. NCT01772849 and NCT01772862. PMID- 24229364 TI - Water-compatible molecularly imprinted microspheres in pipette tip solid-phase extraction for simultaneous determination of five fluoroquinolones in eggs. AB - New water-compatible molecularly imprinted microspheres were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using 3-(2 carboxyethylsulfanylthiocarbonyl-sulfanyl) propionic acid as a hydrophilic chain transfer agent, and employed as the sorbent of pipet tip molecularly imprinted solid-phase extraction (PT-MISPE) for rapid extraction and screening of ofloxacin, pefloxacin, norfloxacin, ciprofloxacin, and enrofloxacin in eggs. In comparison to conventional SPE methods, the presented PT-MISPE showed special selectivity, easy operation, and accessible device without expensive SPE apparatus. The presented PT-MISPE method combined advantages of dummy molecularly imprinted polymers and pipet tip solid-phase extraction. The presented method was linear over a calibration range of 25-2500 MUg/kg with the limits of detections of 0.53-1.07 MUg/kg. Good recoveries (89.1-102.5%) were achieved with relative standard deviations of 2.6-4.8%. PMID- 24229365 TI - Sexual reproductive health service provision to young people in Kenya; health service providers' experiences. AB - BACKGROUND: Addressing the sexual and reproductive health (SRH) needs of young people remains a challenge for most developing countries. This study explored the perceptions and experiences of Health Service Providers (HSP) in providing SRH services to young people in Kenya. METHODS: Qualitative study conducted in eight health facilities; five from Nairobi and three rural district hospitals in Laikipia, Meru Central, and Kirinyaga. Nineteen in-depth interviews (IDI) and two focus group discussions (FGD) were conducted with HSPs. Interviews were tape recorded and transcribed. Data was coded and analysed using the thematic framework approach. RESULTS: The majority of HSPs were aware of the youth friendly service (YFS) concept but not of the supporting national policies and guidelines. HSP felt they lacked competency in providing SRH services to young people especially regarding counselling and interpersonal communication. HSPs were conservative with regards to providing SRH services to young people particularly contraception. HSP reported being torn between personal feelings, cultural and religious values and beliefs and their wish to respect young people's rights to accessing and obtaining SRH services. CONCLUSION: Supporting youth friendly policies and competency based training of HSP are two common approaches used to improve SRH services for adolescents. However, these may not be sufficient to change HSPs' attitude to adolescents seeking help. There is need to address the cultural, religious and traditional value systems that prevent HSPs from providing good quality and comprehensive SRH services to young people. Training updates should include sessions that enable HSPs to evaluate how their personal and cultural values and beliefs influence practice. PMID- 24229366 TI - SrGe2B2O8 and Sr3Ge2B6O16: novel strontium borogermanates with three-dimensional and layered anionic architectures. AB - Two new alkaline-earth strontium borogermanates, namely, SrGe2B2O8 and Sr3Ge2B6O16, have been successfully synthesized through high-temperature solid state reactions. They represent the first examples of strontium borogermanates. SrGe2B2O8 crystallized in space group Pnma, and its structure features a novel three-dimensional [Ge2B2O8](2-) framework composed of alternative linkages of the B2O7 and Ge2O7 dimeric units with one-dimensional (1D) tunnels of eight-membered rings (MRs) along the b axis that are filled by the Sr(2+) cations. Sr3Ge2B6O16 is isostructural with Ba3Ge2B6O16 and crystallizes in centrosymmetric space group P1. Its structure features a two-dimensional layer that is composed of circular B6O16 clusters and GeO4 tetrahedra that are interconnected via corner sharing, forming 1D four- and six-MR tunnels along a axis. Sr(1) cations are located in the six-MR tunnels, whereas Sr(2) cations are located in the interlayer space. Studies of their optical properties and thermal stability as well as band structure calculations based on density functional theory methods have been also performed. PMID- 24229367 TI - A three-year comparative study of continuation rates, bleeding patterns and satisfaction in Australian women using a subdermal contraceptive implant or progestogen releasing-intrauterine system. AB - BACKGROUND Long-acting reversible contraceptive methods (LARCs) are safe, highly effective, readily reversible, and require no action on the part of the user following insertion. Early discontinuation may put women at increased risk of unintended pregnancy. METHODS Following insertion of a progestogen-only subdermal implant or intrauterine system (IUS) at Family Planning NSW, women 18 years and older completed a questionnaire about their choice. At 6 weeks, 6, 12, 24 and 36 months by telephone or online they completed a questionnaire about bleeding patterns, side effects, satisfaction, and reasons for discontinuation. RESULTS Two hundred IUS users and 149 implant users were enrolled. The former were generally older, married or in a de-facto relationship, and had children. Forty seven percent of implant users discontinued within three years compared to 27% of IUS users (p = 0.002). In the first two years amenorrhoea was more frequent in implant users. Frequent bleeding/spotting was more prevalent in the first year of IUS use but over time was twice as prevalent in implant users. Infrequent bleeding/spotting was more common in IUS users. CONCLUSION Both devices are highly effective and acceptable cost-effective methods. While LARCs should be promoted to women of all ages seeking contraception, early discontinuation due to unacceptable bleeding highlights the need for pre-insertion counselling. PMID- 24229368 TI - Molecular recognition of aromatic rings by flavin: electrostatics and dispersion determine ring positioning above isoalloxazine. AB - Aromatic stacking interactions between isoalloxazine (ISA) of flavin and three prototypical aromatics (benzene, pyridine, chlorobenzene) were investigated using electronic structure calculations with Monte Carlo simulated annealing. The Effective Fragment Potential (EFP) method was used to locate the low-energy equilibrium configurations for the three dimer systems. These structures were further characterized through DFT (M06-2X) and MP2 calculations. One equilibrium configuration exists for ISA-benzene; characterizing the stacked dimer surface revealed a steep, single-welled potential that funnels benzene directly between rings II and III, positioning a substituent hydrogen adjacent to the redox-active N5. ISA-pyridine and ISA-chlorobenzene minimum-energy structures contain the aromatic ring in very similar position to that in ISA-benzene. However, the added rotational degree of freedom leads to two distinct binding motifs, having approximately antiparallel or parallel dipole moment alignment with ISA. The existence of the latter binding configuration was unexpected but is explained by the shape of the ISA electrostatic potential. Dispersion is the primary noncovalent interaction driving the positioning of aromatic rings above ISA, while electrostatics determine the orientation in dipole-containing substituted benzenes. The interplay of these interactions can be used to tune molecular recognition properties of synthetic redox cofactors, including positioning desired functional groups adjacent to the redox-active N5. PMID- 24229369 TI - Factors associated with anger and anger expression in caregivers of elderly relatives. AB - OBJECTIVES: Anger is a common feeling among family caregivers of elderly dependents. However, this feeling has received less attention than other emotional effects of caring. This study measures anger in caregivers and analyzes its predictors. METHOD: Trait anger and anger expression (expression-in, expression-out and expression index), caregiver and care recipient features, stressors (e.g. care demands and support), appraisal (e.g. burden) and resources (e.g. coping, self-efficacy) were assessed in 111 caregivers of elderly dependent relatives. Staged stepwise multiple linear regression analyses were carried out for each of the four anger scores. RESULTS: Caregivers presented mild anger levels and showed expression-in rather than expression-out of anger. Stepwise multiple linear regression analyses showed that a bad relationship between caregiver and care recipient, the presence of disruptive behaviors and caregivers' low efficacy to handle them, and mostly the use of emotion-focused coping were the significant predictors of trait anger, anger expression index and anger expression-out. Explained variance for each of these regression models was 38%, 33% and 27%, respectively. Burden was the only significant predictor for internal anger expression (8% explained variance). CONCLUSION: Results highlight that interventions aimed to improve caregivers' strategies to address memory and behavior problems and to promote the use of effective coping strategies could be helpful to prevent anger and expression-out of anger. Reducing burden in caregivers might result in reductions of anger expression-in. Data underscore the need to consider anger feeling and both in-expression and out-expression of anger separately in order to understand anger experience in caregivers. PMID- 24229370 TI - Bisphenol a and its chlorinated derivatives in human colostrum. AB - The health effects related to bisphenol A (BPA) and its exposure sources have undergone extensive investigation, but no consensus has been reached. Hitherto, the major source of human BPA exposure considered in the literature remains food contact material. However, the chlorine present in drinking water may react with BPA to form chlorinated derivatives (ClxBPA), which have indeed been shown to have a heightened level of estrogenic activity. In this study, we have evaluated colostrum concentrations of BPA and ClxBPA in order to confirm our hypothesis according to which BPA water contamination leads to ClxBPA human exposure. BPA and its ClxBPA were assessed through online solid-phase extraction coupled to ultra high-performance liquid chromatography tandem mass spectrometry (SPE-UPLC MS/MS) using the isotope dilution method in the colostrums of 21 women who had completed a water exposure questionnaire. BPA was detected in 19 colostrums and its ClxBPA in 21 colostrums. Mean concentrations were 1.87 +/- 1.38 ng mL(-1) (n = 19) for BPA, 1.87 +/- 1.23 ng mL(-1) (n = 7) and 1.56 +/- 0.74 (n = 18) ng mL( 1) for 2,2'-Cl2BPA and 2,6-Cl2BPA, respectively, and 0.68 ng mL(-1) (n = 1) for trichloro-BPA. These findings confirm our hypothesis that ClxBPA should be taken into account in human health risk assessment. PMID- 24229371 TI - Pre-hypertension: another 'pseudodisease'? AB - Hypertension is one of the most important and common cardiovascular risk factors. Defining the level at which blood pressure starts causing end-organ damage is challenging, and is not easily answered. The threshold of blood pressure defining hypertension has progressively been reduced over time, from systolic >160 mmHg to >150 mmHg, then to >140 mmHg; and now even blood pressures above 130 to 120 mmHg are labeled as 'pre-hypertension' by some expert committees. Are interest groups creating another 'pseudodisease' or is this trend scientifically justified? A recent meta-analysis published in BMC Medicine by Huang et al. clearly indicates that pre-hypertension (120 to 140/80 to 90 mmHg) is a significant marker of increased cardiovascular risk. This raises the question as to whether we now need to lower the threshold of 'hypertension' (as opposed to 'pre-hypertension') to >120/80 mmHg, redefining a significant proportion of currently healthy people as 'patients' with an established disease. These data need to be interpreted with some caution. It is controversial whether pre-hypertension is an independent risk factor or just a risk marker and even more controversial whether treatment of pre hypertension will lower cardiovascular risk. Please see related research: http://www.biomedcentral.com/1741-7015/11/177. PMID- 24229372 TI - Classification of Nonallergic Rhinitis Syndromes With a Focus on Vasomotor Rhinitis, Proposed to be Known henceforth as Nonallergic Rhinopathy. AB - Many patients have nasal syndromes that are nonallergic and noninfectious and not caused by mechanical or anatomic abnormalities. There are at least 8 recognized nonallergic rhinitis syndromes: drug-induced rhinitis including rhinitis medicamentosa, gustatory rhinitis, hormonally induced rhinitis including the rhinitis of pregnancy, nonallergic rhinitis with eosinophilia syndrome, senile rhinitis, atrophic rhinitis, cerebral spinal fluid leak, and vasomotor rhinitis. Few studies have explored etiologic causes. These syndromes are distinguished by clinical characteristics, recognized triggering conditions, and concomitant observations such as nasal eosinophilia or cerebral spinal fluid leak. Until more specific subjective clinical characteristics and/or objective measures can better define and differentiate underlying causes for these disparate diseases, they will remain a murky group of overlapping syndromes. PMID- 24229373 TI - Influence network linkages across implementation strategy conditions in a randomized controlled trial of two strategies for scaling up evidence-based practices in public youth-serving systems. AB - BACKGROUND: Given the importance of influence networks in the implementation of evidence-based practices and interventions, it is unclear whether such networks continue to operate as sources of information and advice when they are segmented and disrupted by randomization to different implementation strategy conditions. The present study examines the linkages across implementation strategy conditions of social influence networks of leaders of youth-serving systems in 12 California counties participating in a randomized controlled trial of community development teams (CDTs) to scale up use of an evidence-based practice. METHODS: Semi structured interviews were conducted with 38 directors, assistant directors, and program managers of county probation, mental health, and child welfare departments. A web-based survey collected additional quantitative data on information and advice networks of study participants. A mixed-methods approach to data analysis was used to create a sociometric data set (n = 176) to examine linkages between treatment and standard conditions. RESULTS: Of those network members who were affiliated with a county (n = 137), only 6 (4.4%) were directly connected to a member of the opposite implementation strategy condition; 19 (13.9%) were connected by two steps or fewer to a member of the opposite implementation strategy condition; 64 (46.7%) were connected by three or fewer steps to a member of the opposite implementation strategy condition. Most of the indirect steps between individuals who were in different implementation strategy conditions were connections involving a third non-county organizational entity that had an important role in the trial in keeping the implementation strategy conditions separate. When these entities were excluded, the CDT network exhibited fewer components and significantly higher betweenness centralization than did the standard condition network. CONCLUSION: Although the integrity of the RCT in this instance was not compromised by study participant influence networks, RCT designs should consider how influence networks may extend beyond boundaries established by the randomization process in implementation studies. TRIAL REGISTRATION: NCT00880126. PMID- 24229374 TI - Influence of NADPH oxidase on inflammatory response in primary intestinal epithelial cells in patients with ulcerative colitis. AB - BACKGROUND: The aim of this study is to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC. METHODS: The primary human colonic epithelial cells were isolated from 19 patients with mild to moderate inflammatory activity of UC and 14 controls using chelation method. The cells were cultivated under the effect of mediators. Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorimetrically using Amplex Red. Production of TNF alpha cytokine by the colonic epithelial cells was analysed by ELISA. RESULTS: The results of our study showed that unstimulated cells of UC patients had a decreased viability, increased ROS production, but similar TNF-alpha level when compared to the controls. Stimulation with LPS increased hydrogen peroxide and TNF-alpha level in the UC group. Treatment of colonic epithelial cells with NADPH oxidase inhibitor increased cell viability decreased the levels of ROS and TNF alpha in the LPS-treated cells isolated from UC patients. CONCLUSIONS: Our study showed that bacterial endotoxins induced NADPH oxidase activation in the colonic epithelial cells. Moreover, we revealed that treatment with NADPH oxidase inhibitors had a protective effect against pro-inflammatory action of LPS in human colonic epithelium cells during inflammation. PMID- 24229375 TI - The effect of uniaxial strain on graphene nanoribbon carrier statistic. AB - : Armchair graphene nanoribbon (AGNR) for n=3m and n=3m+1 family carrier statistic under uniaxial strain is studied by means of an analytical model based on tight binding approximation. The uniaxial strain of AGNR carrier statistic models includes the density of state, carrier concentration, and carrier velocity. From the simulation, it is found that AGNR carrier concentration has not been influenced by the uniaxial strain at low normalized Fermi energy for n=3m and n=3m+1. In addition, the carrier velocity of AGNR is mostly affected by strain at high concentration of n~3.0*107 and 1.0 * 107 m-1 for n=3m and n=3m+1, respectively. The result obtained gives physical insight into the understanding of uniaxial strain in AGNR. PMID- 24229376 TI - Seroprevalence and trend of Helicobacter pylori infection in Gondar University Hospital among dyspeptic patients, Gondar, North West Ethiopia. AB - BACKGROUND: The growing attention given to H. pylori is not surprising since this pathogen colonizes more than at least half of the world's inhabitants. In Ethiopia particularly in Gondar, there is no current study conducted about seroprevalence and trend of the prevalence of H. pylori. Therefore the aim of this study was to determine the seroprevalence and its trend of the H. pylori in three consecutive years in North Gondar, North West Ethiopia. FINDINGS: Retrospective study was conducted using data collected from log book of serology laboratory of Gondar University Hospital. We collected data from January 2009 to December 2011 and 1388 subjects were included whose data were registered completely.Among all of the study subjects, 912 (65.7%) were found to be seropositive. The prevalence in male was 449/679 (66.1%) and in females it was 463/709 (65.3%). The prevalence of H.pylori infection was significantly higher (77.0%) in patients whose age is greater than 60 years and the lowest positive age group was between 0-20 in which only 59.1% were positive (X2 =14.15,p=0.0146). The seroprevalence was 86.5% in 2009 and it decreased to 51.8% in 2010. But the seroprevalence increased to 61.3% in 2011. CONCLUSION: This study showed high seroprevalence of H. pylori among the dyspeptic patients in GUH. The trend of the seroprevalence was varied from year to year in the three consecutive years. In general it showed that the seroprevalence has started increasing. PMID- 24229378 TI - Inhibition of poly (adenosine diphosphate-ribose) polymerase attenuates lung kidney crosstalk induced by intratracheal lipopolysaccharide instillation in rats. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of lung injury that frequently occurs during pneumonia and sepsis. Lung inflammation in ARDS patients may have deleterious effects on remote organs such as the kidney. The nuclear enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) enhances the nuclear factor (NF)-kappaB-dependent transcription of inflammatory cytokines. This study was conducted to elucidate two questions: first, whether the activation of PARP and NF-kappaB mediates the renal inflammation secondary to the lipopolysaccharide (LPS)-induced acute lung inflammation; second, whether a PARP inhibitor, 3-aminobenzamide (3-AB), attenuates lung and kidney inflammation by inhibiting NF-kappaB-dependent proinflammatory cytokines. METHODS: Male Sprague Dawley rats were anesthetized, ventilated, and divided into three groups; a control group (n = 8); an LPS group (n = 12) intratracheally instilled with LPS (16 mg/kg), and an LPS + 3-AB group (n = 12) given the same dose of LPS by the same method followed by an intravenous injection of 3-AB (20 mg/kg). Hemodynamics, arterial blood gas, and the plasma levels of lactate, creatinine and potassium were measured at 0,1,2,3, and 4 h after treatment. The lung wet/dry ratio was measured at 4 h. The mRNA expression of tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta and IL-6 in the lung and kidney were measured by TaqMan real-time PCR. PARP and NF-kappaB in the lung and kidney were histologically examined by immunostaining and assigned expression scores. RESULTS: LPS induced metabolic acidosis, hypotension, hypoxemia, increased the lung wet/dry ratio, increased the plasma levels of creatinine and potassium, and increased the cytokine mRNA expressions in the lung and kidney. All of these effects were associated with strong expression of PARP and NF-kappaB. Treatment with 3-AB prevented the LPS-induced metabolic acidosis and hypotension, reduced the plasma levels of lactate, creatinine and potassium, reduced the cytokine mRNA expressions, reduced the expression of PARP and NF-kappaB, improved pulmonary edema and oxygenation and preserved renal function. CONCLUSIONS: The PARP inhibition attenuated lung-kidney crosstalk induced by intratracheal LPS instillation, partly via an inhibition of NF-kappaB dependent proinflammatory cytokines. PMID- 24229379 TI - PIK3R1 underexpression is an independent prognostic marker in breast cancer. AB - BACKGROUND: The present study focused on the prognostic roles of PIK3CA and PIK3R1 genes and additional PI3K pathway-associated genes in breast cancer. METHODS: The mutational and mRNA expression status of PIK3CA, PIK3R1 and AKT1, and expression status of other genes involved in the PI3K pathway (EGFR, PDK1, PTEN, AKT2, AKT3, GOLPH3, WEE1, P70S6K) were assessed in a series of 458 breast cancer samples. RESULTS: PIK3CA mutations were identified in 151 samples (33.0%) in exons 1, 2, 9 and 20. PIK3R1 mutations were found in 10 samples (2.2%) and underexpression in 283 samples (61.8%). AKT1 mutations were found in 15 samples (3.3%) and overexpression in 116 samples (25.3%). PIK3R1 underexpression tended to mutual exclusivity with PIK3CA mutations (p = 0.00097). PIK3CA mutations were associated with better metastasis-free survival and PIK3R1 underexpression was associated with poorer metastasis-free survival (p = 0.014 and p = 0.00028, respectively). By combining PIK3CA mutation and PIK3R1 expression status, four prognostic groups were identified with significantly different metastasis-free survival (p = 0.00046). On Cox multivariate regression analysis, the prognostic significance of PIK3R1 underexpression was confirmed in the total population (p = 0.0013) and in breast cancer subgroups. CONCLUSIONS: PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer. PMID- 24229380 TI - The UKCAT-12 study: educational attainment, aptitude test performance, demographic and socio-economic contextual factors as predictors of first year outcome in a cross-sectional collaborative study of 12 UK medical schools. AB - BACKGROUND: Most UK medical schools use aptitude tests during student selection, but large-scale studies of predictive validity are rare. This study assesses the United Kingdom Clinical Aptitude Test (UKCAT), and its four sub-scales, along with measures of educational attainment, individual and contextual socio-economic background factors, as predictors of performance in the first year of medical school training. METHODS: A prospective study of 4,811 students in 12 UK medical schools taking the UKCAT from 2006 to 2008 as a part of the medical school application, for whom first year medical school examination results were available in 2008 to 2010. RESULTS: UKCAT scores and educational attainment measures (General Certificate of Education (GCE): A-levels, and so on; or Scottish Qualifications Authority (SQA): Scottish Highers, and so on) were significant predictors of outcome. UKCAT predicted outcome better in female students than male students, and better in mature than non-mature students. Incremental validity of UKCAT taking educational attainment into account was significant, but small. Medical school performance was also affected by sex (male students performing less well), ethnicity (non-White students performing less well), and a contextual measure of secondary schooling, students from secondary schools with greater average attainment at A-level (irrespective of public or private sector) performing less well. Multilevel modeling showed no differences between medical schools in predictive ability of the various measures. UKCAT sub scales predicted similarly, except that Verbal Reasoning correlated positively with performance on Theory examinations, but negatively with Skills assessments. CONCLUSIONS: This collaborative study in 12 medical schools shows the power of large-scale studies of medical education for answering previously unanswerable but important questions about medical student selection, education and training. UKCAT has predictive validity as a predictor of medical school outcome, particularly in mature applicants to medical school. UKCAT offers small but significant incremental validity which is operationally valuable where medical schools are making selection decisions based on incomplete measures of educational attainment. The study confirms the validity of using all the existing measures of educational attainment in full at the time of selection decision making. Contextual measures provide little additional predictive value, except that students from high attaining secondary schools perform less well, an effect previously shown for UK universities in general. PMID- 24229382 TI - Exciton-free, nonsensitized degradation of 2-naphthol by facet-dependent BiOCl under visible light: novel evidence of surface-state photocatalysis. AB - Photoreactivity for photodegradation of 2-NAP on BiOCl nanosheets with dominant exposed (010) and (001) facets is studied under visible light via an exciton-free and nonsensitized mechanism. This phenomenon cannot be explained by semiconductor theory or self-sensitized (as those involve dyes) mechanisms. The photocatalytic activities are mainly owing to the formation of the surface state, which is confirmed to be the surface complex Bi-O-C10H7. This surface complex is characterized with ultraviolet-visible diffuse reflectance spectra, Fourier transformed infrared spectroscopy, Raman scattering, X-ray photoelectron spectroscopy, and photoelectrochemical measurement. The optical absorptivity of BiOCl is shifted from the ultraviolet light toward the visible light via a charge transfer-complex pathway. Charge transfer after the excitation of visible light induces efficient visible photocatalytic activities. The results show that single crystalline BiOCl nanosheets exposing (010) facets exhibit higher photoactivity due to more surface complex and more terminal bismuth atoms on the surface of BiOCl (010). Our current work is expected to offer new insight into photocatalytic theory for better understandings to photocatalytic reactions and for rational design and synthesis of photocatalyst with high activity. PMID- 24229381 TI - The impact of implant treatment on oral health related quality of life in a private dental practice: a prospective cohort study. AB - BACKGROUND: Very few studies on the impact of implant therapy on Oral Health Related Quality of Life (OHRQoL) in partially edentulous patients have been published. AIM: This study aimed at analysing the improvement of OHRQoL of patients who underwent dental implant treatment using the "functional", "psychosocial" and "pain and discomfort" categories of the Geriatric Oral Health Assessment Index (GOHAI). METHODS: Within a prospective cohort of patients rehabilitated with Straumann dental implants, the OHRQoL of 176 patients (104 women and 72 men) was assessed using the GOHAI questionnaire, at two different times, before and after implant placement. The degree of oral treatment was categorised into three classes: "Single Tooth Implant" (n = 77), "Fixed Partial Denture" (n = 75), "Fixed or Retained Full Prostheses" (n = 24). The participants' characteristics (gender, age, tobacco habits, periodontal treatment, time between both evaluations) were assessed. RESULTS: Before treatment, the GOHAI score was lower for participants with fewer teeth (F = 19, P < 0.001). After treatment, no difference was observed between participants; significant improvements were observed in the GOHAI scores obtained (repeated measures, analysis, (F = 177, P < 0.001)) for each of the GOHAI fields studied (functional, psychosocial and pain & discomfort), regardless of the degree of treatment. The best improvement was observed in patients who needed complete treatment (P < 0.001). The presence of preliminary periodontal treatment, tobacco habits, age and gender of the participants did not have a significant impact on OHRQoL. Changing the time between the two evaluations (before and after treatment) had no impact on the changes in the GOHAI score. CONCLUSIONS: Implants enhanced the OHRQoL of participants that needed oral treatment. PMID- 24229383 TI - Home-based behavioral sleep training for shift workers: a pilot study. AB - This pilot study evaluated a home-based cognitive-behavioral intervention-the Sleep Enhancement Training System for Shift Workers (SETS-SW)-in a sample of 21 nurses working night shifts. Participants (20 women and 1 man) received 2 home based cognitive-behavioral interventions: a 4-week active control intervention, followed by the 4-week SETS-SW intervention. Sleep and circadian rhythms were assessed at baseline and after each intervention using questionnaires and 1 week of wrist actigraphy. After the SETS-SW intervention, participants reported better sleep quality, although no change in actigraphy outcomes was observed. Over the course of the study, participants also reported improved wellbeing and less appetite disturbance. A home-based cognitive-behavioral intervention may be useful for managing effects of shift work, but needs further evaluation in larger samples. PMID- 24229384 TI - Minimum light intensity threshold to prevent negative effects on broiler production and welfare. AB - 1. Research focused on lower light intensity levels is required to set minimum standards appropriate for production and welfare of intensively housed broilers. The objective of this research was to study light intensity (0.1 to 10 lx) effects on Ross * Ross 308 and 708 genotypes. 2. Three experiments (35 d each) using 18 720 broilers were conducted with the initial experiment using two replicates of 0.1, 1, 5 and 10 lx. The second and third experiments examined 0.5, 1, 5 and 10 lx with treatments replicated twice in each experiment in a randomised complete block design with experiment acting as a block. In each experiment, mixed sex broilers from each genotype were housed in 6 equally sized pens per room. 3. In Experiment 1, the introduction of 0.1 lx at d 7 caused high levels of mortality and poor growth rate from d 7 to 14 and was discontinued. 4. In Experiments 2 and 3, increasing light intensity increased body weight gain (0 35 d) and feed intake (0-35 d) in a quadratic and linear fashion, respectively. Similarly, mortality corrected gain to feed ratio (FCR, 0-35 d) demonstrated a quadratic response with a maximum at 5 lx. Carcass, breast meat and skin, abdominal fat and drum skin, as a percentage of live weight, increased while drum bone and wing yield decreased in a linear fashion with increasing light intensity. Total carcass composition was unaffected by light intensity. 5. Genotype effects were numerous. No interactions were found between genotype and light intensity. 6. Ocular dimensions and the incidence of foot pad lesions decreased in a quadratic and linear fashion, respectively, with increasing light intensity. In contrast, welfare-associated gait score and mortality levels were not affected by light intensity. 7. It was concluded that performance, breast meat yield and bird welfare improved with increasing light intensity. The data support 5 lx as a minimum light intensity in broiler production. PMID- 24229385 TI - High-throughput quantitative biochemical characterization of algal biomass by NIR spectroscopy; multiple linear regression and multivariate linear regression analysis. AB - One of the challenges associated with microalgal biomass characterization and the comparison of microalgal strains and conversion processes is the rapid determination of the composition of algae. We have developed and applied a high throughput screening technology based on near-infrared (NIR) spectroscopy for the rapid and accurate determination of algal biomass composition. We show that NIR spectroscopy can accurately predict the full composition using multivariate linear regression analysis of varying lipid, protein, and carbohydrate content of algal biomass samples from three strains. We also demonstrate a high quality of predictions of an independent validation set. A high-throughput 96-well configuration for spectroscopy gives equally good prediction relative to a ring cup configuration, and thus, spectra can be obtained from as little as 10-20 mg of material. We found that lipids exhibit a dominant, distinct, and unique fingerprint in the NIR spectrum that allows for the use of single and multiple linear regression of respective wavelengths for the prediction of the biomass lipid content. This is not the case for carbohydrate and protein content, and thus, the use of multivariate statistical modeling approaches remains necessary. PMID- 24229386 TI - Synthesis and selective topochemical fluorination of the cation and anion-vacancy ordered phases Ba2YCoO5 and Ba3YCo2O7.5. AB - The synthesis and characterization of two cation-ordered, anion-vacancy ordered phases, Ba2YCoO5 and Ba3YCo2O7.5, is described. Neutron powder diffraction data reveal both phases adopt structures in which octahedral Y(3+) and tetrahedral Co(3+) centers are ordered within a "cubic" perovskite lattice. The unusual ordered pattern adopted by the cations can be attributed to the large concentration of anion vacancies within each phase. Reaction of Ba2YCoO5 with CuF2 under flowing oxygen topochemically inserts fluorine into the host material to form Ba2YCoO5F0.42(1). In contrast Ba2YCoO5 does not intercalate oxygen, even under high oxygen pressure. The selective insertion of fluorine, but not oxygen, into Ba2YCoO5 is discussed and rationalized on the basis of the lattice strain of the resulting oxidized materials. Magnetization and neutron diffraction data reveal Ba3YCo2O7.5 and Ba2YCoO5F0.42 adopt antiferromagnetically ordered states at low-temperature, while in contrast Ba2YCoO5 shows no sign of long-range magnetic order. PMID- 24229388 TI - Activation of microglial neuregulin1 signaling in the corticospinal tracts of ALS patients with upper motor neuron signs. AB - We recently found neuregulin1 (NRG1) receptors are activated on microglia in the ventral horn of both ALS patients and SOD1 mice, suggesting a common pathological mechanism. However, it is not clear whether this signaling system also plays a role in patients with upper motor neuron (UMN) features, where patients show significant pathological changes in the corticospinal tracts (CSTs). Since the connection between upper and lower motor neuron (LMN) systems in ALS patients is not readily seen in the SOD1 mouse, we examined the lateral and ventral CSTs for NRG1 receptor activation and NRG1 expression in ALS patients with UMN symptoms compared to control patients with no evidence of neurodegenerative disease. We found that ALS patients with UMN symptoms showed increased microglial activation that colocalized with NRG1 receptor activation in the lateral and ventral CSTs. These same regions also showed increased NRG1 protein expression locally but no change in NRG1 mRNA. In conclusion, these data suggest that increased NRG1 protein accumulation could contribute to UMN disease through microglial activation in the CSTs. PMID- 24229389 TI - Gender differences in the association of perceived social support and social network with self-rated health status among older adults: a population-based study in Brazil. AB - BACKGROUND: Older adults are more likely to live alone, because they may have been predeceased by their spouse and friends. Social interaction could also be reduced in this age group due by limited mobility caused by chronic conditions. Therefore, aging is frequently accompanied by reduced social support, which might affect health status. Little is known about the role of gender in the relationship between social support and health in older adults. Hence, the present study tests the hypothesis that gender differences exist in the relationship between perceived social support, social network, and self-rated health (SRH) among older adults. METHODS: A cross-sectional study using two-stage probabilistic sampling recruited 3,649 individuals aged 60 years and above. Data were collected during the national influenza vaccination campaign in Rio de Janeiro, Brazil, in 2006. Individual interviews collected information on SRH, perceived social support, social network, and other covariates. Multivariate logistic regression analyses using nested models were conducted separately for males and females. Independent variables were organised into six blocks: (1) perceived social support and social network, (2) age group, (3) socioeconomic characteristics, (4) health-related behaviours, (5) use of health care services, (6) functional status measures and somatic health problems. RESULTS: Older men who did not participate in group activities were more likely to report poor SRH compared to those who did, (OR = 1.63; 95% CI = 1.16-2.30). Low perceived social support predicted the probability of poor SRH in women (OR = 1.64; 95% CI = 1.16 2.34). Poor SRH was associated with low age, low income, not working, poor functional capacity, and depression in both men and women. More somatic health problems were associated with poor SRH in women. CONCLUSIONS: The association between social interactions and SRH varies between genders. Low social network involvement is associated with poor SRH in older men, whereas low perceived social support is associated with poor SRH in older women. The hypothesis that the relationship of perceived social support and social networks to SRH differs according to gender has been confirmed. PMID- 24229390 TI - Pregnancy planning and lifestyle prior to conception and during early pregnancy among Danish women. AB - OBJECTIVE To investigate the extent to which Danish women attending antenatal care plan their pregnancies and to determine the association between pregnancy planning and the intake of folic acid, alcohol consumption and smoking habits prior to conception and before the 16th week of gestation. METHODS A cross sectional survey of 258 women. MAIN OUTCOME MEASURES: intake of folic acid, alcohol consumption and smoking. Pregnancy planning was assessed by the London Measure of Unplanned Pregnancy (LMUP) and the five graded Swedish Pregnancy Planning Scale. RESULTS Most (77%) of the participants reported that their pregnancies were very or fairly well planned. Higher median LMUP scores were observed in women taking folic acid (p < 0.001), in those consuming less alcohol, and in women who stopped smoking prior to pregnancy (p = 0.043). However, 43% of the respondents with a high degree of pregnancy planning and 98% of those with a low degree of planning had not taken folic acid prior to pregnancy. Binge drinking during early pregnancy was reported by 20% of women with a high degree of planned pregnancy and 31% of those with a low degree (p = 0.1). CONCLUSION Pregnancy planning was associated with a healthier lifestyle but still many women could improve their lifestyle in connection to pregnancy. Their level of alcohol consumption is higher than that recommended for best pregnancy outcome. PMID- 24229393 TI - Solution-processed nanocomposites containing molybdenum oxide and gold nanoparticles as anode buffer layers in plasmonic-enhanced organic photovoltaic devices. AB - Solution-processed nanocomposites containing molybdenum oxide (MoO3) and gold nanoparticles (Au NPs) have been used as anode buffer layers in organic photovoltaic devices (OPVs). The resulting devices exhibit a remarkable enhancement in power conversion efficiency after Au NPs were incorporated into the device. Such enhancements can be attributed to the localized surface plasmon resonance induced by the metallic nanostructures. We have also found that the rate of exciton generation and the probability of exciton dissociation were increased. Furthermore, the devices made of the MoO3 buffer layer containing Au NPs exhibited superior stability. This work opens up the possibility of fabricating OPVs with both high efficiency and a prolonged lifetime. PMID- 24229392 TI - Characterization of a chemostable serine alkaline protease from Periplaneta americana. AB - BACKGROUND: Proteases are important enzymes involved in numerous essential physiological processes and hold a strong potential for industrial applications. The proteolytic activity of insects' gut is endowed by many isoforms with diverse properties and specificities. Thus, insect proteases can act as a tool in industrial processes. RESULTS: In the present study, purification and properties of a serine alkaline protease from Periplaneta americana and its potential application as an additive in various bio-formulations are reported. The enzyme was purified near to homogeneity by using acetone precipitation and Sephadex G 100 gel filtration chromatography. Enzyme activity was increased up to 4.2 fold after gel filtration chromatography. The purified enzyme appeared as single protein-band with a molecular mass of ~ 27.8 kDa in SDS-PAGE. The optimum pH and temperature for the proteolytic activity for purified protein were found around pH 8.0 and 60 degrees C respectively. Complete inhibition of the purified enzyme by phenylmethylsulfonyl fluoride confirmed that the protease was of serine-type. The purified enzyme revealed high stability and compatibility towards detergents, oxidizing, reducing, and bleaching agents. In addition, enzyme also showed stability towards organic solvents and commercial detergents. CONCLUSION: Several important properties of a serine protease from P. Americana were revealed. Moreover, insects can serve as excellent and alternative source of industrially important proteases with unique properties, which can be utilized as additives in detergents, stain removers and other bio-formulations. Properties of the P. americana protease accounted in the present investigation can be exploited further in various industrial processes. As an industrial prospective, identification of enzymes with varying essential properties from different insect species might be good approach and bioresource. PMID- 24229394 TI - Adherence to Antiretroviral Therapy and associated factors among HIV infected children in Ethiopia: unannounced home-based pill count versus caregivers' report. AB - BACKGROUND: The introduction of Antiretroviral Therapy (ART) has brought a remarkable reduction in HIV-related mortality and morbidity both in adults and children living with HIV/AIDS. Adherence to ART is the key to the successful treatment of patients as well as containment of drug resistance. Studies based on caregivers' report have shown that adherence to ART among children is generally good. However, subjective methods such as caregivers' report are known to overestimate the level of adherence. This study determined the rate of adherence and its predictors using unannounced home-based pill count and compared the result with caregivers' report in a tertiary referral hospital in Ethiopia. METHODS: A cross-sectional study was conducted between December 1, 2011 and January 30, 2012. The study participants were 210 children on ART and their caregivers attending pediatric ART clinic of Tikur Anbessa Hospital (TAH), Addis Ababa University. Caregivers were interviewed at the ART clinic using a structured questionnaire. Then, unannounced home-based pill count was done 7 days after the interview. RESULTS: Caregiver-reported adherence in the past 7 days prior to interview was 93.3%. Estimated adherence using unannounced home-based pill count was found, however, to be 34.8%. On multivariate logistic regression model, children with married [aOR = 7.85 (95% CI: 2.11,29.13)] and widowed/divorced [aOR = 7.14 (95% CI: 2.00,25.46)] caregivers, those who were not aware of their HIV sero-status [aOR = 2.35 (95% CI:1.09, 5.06)], and those with baseline WHO clinical stage III/IV [OR = 3.18 (95% CI: 1.21, 8.40] were more likely to adhere to their ART treatment. On the other hand, children on d4T/3Tc/EFV combination [OR = 0.10 (95% CI: 0.02, 0.53)] were less likely to adhere to their treatment. Caregivers' forgetfulness and child refusal to take medication were reported as the major reasons for missing doses. CONCLUSION: The level of adherence based on unannounced home-based pill count was unacceptably low. Interventions are urgently needed to improve adherence to ART among children at TAH. Besides, a longitudinal study measuring adherence combined with clinical parameters (viral load and CD4 count) is needed to identify a simple and reliable measure of adherence in the study area. PMID- 24229395 TI - Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. AB - PURPOSE: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy. EXPERIMENTAL DESIGN: IP 212Pb-TCMC-trastuzumab was delivered, after 4 mg/kg intravenous (IV) trastuzumab, to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters. RESULTS: Imaging studies after 0.2 mCi/m2 (7.4 MBq/m2) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was <=6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67 mR/h and dropped to 0.67 mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with 212Pb physical decay (T1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity. CONCLUSIONS: Pharmacokinetics and imaging after 0.2 mCi/m2 IP 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, <=6% urinary excretion, and good tolerance. PMID- 24229396 TI - The lactic acid bacteria metabolite phenyllactic acid inhibits both radial growth and sporulation of filamentous fungi. AB - BACKGROUND: Food spoilage caused by molds is a severe problem. In food and feed, e.g. dairy products, sourdough bread and silage, lactic acid bacteria are used as starter cultures. Besides lactic and acetic acid, some strains produce other low molecular weight compounds with antifungal activities. One of these metabolites is phenyllactic acid (PLA), well known for its antifungal effect. The inhibitory effect of PLA has only partially been investigated, and the objective of this study was to elucidate in detail the antifungal properties of PLA. RESULTS: We investigated the outgrowth of individual conidia from Aspergillus niger, Cladosporium cladosporioides and Penicillium roqueforti, and observed the morphologies of resulting colonies on solid media using different acid concentrations. We found that PLA inhibits molds similar to weak acid preservatives. Furthermore, it has an additional activity: at sub-inhibitory concentrations, fungal colonies displayed slower radial growth and inhibited sporulation. The L isoform of PLA is a more potent inhibitor than the D form. Increased expression of phiA was observed during PLA treatment. This gene was initially identified as being induced by Streptomyces-produced macrolide antibiotics, and is shown to be a structural protein in developed cells. This suggests that PhiA may act as a general stress protectant in fungi. CONCLUSION: From a food protection perspective, the results of this study support the usage of lactic acid bacteria strains synthesizing PLA as starter cultures in food and feed. Such starter cultures could inhibit spore synthesis, which would be beneficial as many food borne fungi are spread by airborne spores. PMID- 24229399 TI - "Sleep well, our tough heroes!"--in adolescence, greater mental toughness is related to better sleep schedules. AB - Mental toughness (MT) is understood as the display of confidence, commitment, challenge, and control. The aim of this study was to explore the extent to which greater MT is associated with subjectively assessed sleep among adolescents. A total of 284 adolescents (M = 18.26 years) completed a series of questionnaires assessing MT, psychological functioning, and sleep. Greater MT was significantly associated with better sleep quality, shorter sleep onset latency, fewer awakenings after sleep onset, and longer sleep duration. Greater MT was also associated with less perceived stress and less depressive symptoms. MT was directly and indirectly associated with sleep quality. Mentally tough adolescents report good sleep quality and sleep schedules, along with psychological wellbeing. PMID- 24229397 TI - Selecting the right medical student. AB - Medical student selection is an important but difficult task. Three recent papers by McManus et al. in BMC Medicine have re-examined the role of tests of attainment of learning (A' levels, GCSEs, SQA) and of aptitude (AH5, UKCAT), but on a much larger scale than previously attempted. They conclude that A' levels are still the best predictor of future success at medical school and beyond. However, A' levels account for only 65% of the variance in performance that is found. Therefore, more work is needed to establish relevant assessment of the other 35%. Please see related research articles http://www.biomedcentral.com/1741 7015/11/242, http://www.biomedcentral.com/1741-7015/11/243 and http://www.biomedcentral.com/1741-7015/11/244. PMID- 24229401 TI - Remote patient monitoring based on ZigBee: lessons from a real-world deployment. AB - AIM: This work presents detailed experimental performance results from tests executed in the hospital environment for Health Monitoring for All (HM4All), a remote vital signs monitoring system based on a ZigBee(r) (ZigBee Alliance, San Ramon, CA) body sensor network (BSN). MATERIALS AND METHODS: Tests involved the use of six electrocardiogram (ECG) sensors operating in two different modes: the ECG mode involved the transmission of ECG waveform data and heart rate (HR) values to the ZigBee coordinator, whereas the HR mode included only the transmission of HR values. In the absence of hidden nodes, a non-beacon-enabled star network composed of sensing devices working on ECG mode kept the delivery ratio (DR) at 100%. RESULTS: When the network topology was changed to a 2-hop tree, the performance degraded slightly, resulting in an average DR of 98.56%. Although these performance outcomes may seem satisfactory, further investigation demonstrated that individual sensing devices went through transitory periods with low DR. Other tests have shown that ZigBee BSNs are highly susceptible to collisions owing to hidden nodes. Nevertheless, these tests have also shown that these networks can achieve high reliability if the amount of traffic is kept low. Contrary to what is typically shown in scientific articles and in manufacturers' documentation, the test outcomes presented in this article include temporal graphs of the DR achieved by each wireless sensor device. CONCLUSIONS: The test procedure and the approach used to represent its outcomes, which allow the identification of undesirable transitory periods of low reliability due to contention between devices, constitute the main contribution of this work. PMID- 24229402 TI - Influence of cation substitution and activator site exchange on the photoluminescence properties of Eu3+-doped quaternary pyrochlore oxides. AB - Stannate-based pyrochlore-type red phosphors CaGd(1-x)SnNbO7:xEu(3+), Ca(1 y)Sr(y)Gd(1-x)SnNbO7:xEu(3+), and Ca(0.8-x)Sr0.2GdSnNbO(7+delta): xEu(3+) were prepared via conventional solid-state method. Influence of cation substitution and activator site control on the photoluminescence properties of these phosphors are elucidated using powder X-ray diffraction, Rietveld analysis, Raman spectrum analysis, and photoluminescence excitation and emission spectra. The Eu(3+) luminescence in quaternary pyrochlore lattice exemplifies as a very good structural probe for the detection of short-range disorder in the lattice, which otherwise is not detected by normal powder X-ray diffraction technique. The Eu(3+) emission due to magnetic dipole transition ((5)D0-(7)F1 MD) is modified with the increase in europium concentration in the quaternary pyrochlore red phosphors. (5)D0-(7)F1 MD transition splitting is not observable for low Eu(3+) doping because of the short-range disorder in the pyrochlore lattice. Appearance of narrow peaks in Raman spectra confirms that short-range disorder in the crystal lattice disappears with progressive europium doping. By using Sr as a network modifier ion in place of Ca we were able to increase the f-f transition intensities and europium quenching concentration. The influence of effective positive charge of the central Eu(3+) ions when it replaces a metal ion having lower oxidation state such as Ca(2+) was also investigated. The relative intensities of A1g (~500 cm(-1)) and F2g (~330 cm(-1)) Raman vibrational modes get inverted when Eu(3+) ions replaces Ca(2+) ions instead of Gd(3+) as trivalent europium ions can attract the electron cloud of oxygen ions strongly in comparison with divalent calcium ions. The influence of positive charge effect of Eu(3+) in Ca0.7Sr0.2GdSnNbO7+delta:0.1Eu(3+) phosphor is greatly strengthened the charge transfer band and (7)F0-(5)L6 transition intensities than that of the Ca0.8Sr0.2Gd0.9SnNbO7:0.1Eu(3+) phosphor. Our results suggest that the photoluminescence properties can be enhanced by simple compositional adjustments in the quaternary pyrochlore-type red phosphors. PMID- 24229403 TI - Tracking of aerobic fitness from adolescence to mid-adulthood. AB - BACKGROUND: Although adults' aerobic fitness is known to be correlated with cardiovascular disease risk, the longitudinal relationship with adolescent aerobic fitness is poorly described. AIM: To longitudinally investigate the relationship between aerobic fitness during adolescence and adulthood. SUBJECTS AND METHODS: Participants (207 boys, 149 girls) aged 7-17 years performed annual measures of VO2peak. In adulthood (40 and 50 years), 78 individuals (59 males and 18 females) were reassessed. Serial height measurements were used to estimate age at peak height velocity (APHV). During adolescence, VO2peak was measured via a treadmill test to voluntary exhaustion; adult VO2peak was assessed using submaximal predictive tests. Correlations were tested using Spearman's rho. ANCOVA was used to assess adult VO2peak group differences based off APHV VO2peak groupings (low, average or high). RESULTS: When sexes were pooled, moderate tracking existed from 2 years prior to APHV to APHV and APHV to 2 years after APHV (0.46, p < 0.001 and 0.35, p < 0.01, respectively). Correlations between APHV and adult values were low when sexes were pooled (p < 0.05). Comparisons of aggregated sexes revealed the low adolescent VO2peak group had lower values in adulthood relative to other groups (p < 0.05). CONCLUSION: Aerobic fitness has a low tracking between APHV and adulthood. PMID- 24229404 TI - Prevalence and determinants of adherence to HAART amongst PLHIV in a tertiary health facility in south-south Nigeria. AB - BACKGROUND: Adherence to Highly active antiretroviral therapy (HAART) is a major predictor of the success of HIV/AIDS treatment. Good adherence to HAART is necessary to achieve the best virologic response, lower the risk of drug resistance and reduce morbidity and mortality. This study therefore aimed to determine the prevalence and determinants of adherence to HAART amongst PLHIV accessing treatment in a tertiary location in Cross River State, Nigeria. METHODS: A cross-sectional study was conducted among patients on HAART attending the Presidential Emergency plan for AIDS relief (PEPFAR) clinic of the University of Calabar Teaching Hospital between October-December 2011. A total of 411 PLHIV visiting the study site during the study period were interviewed. PLHIV who met the inclusion criteria were consecutively recruited into the study till the desired sample size was attained. Information was obtained from participants using a semi-structured, pretested, interviewer administered questionnaire. Adherence was measured via patients self report and were termed adherent if they took at least 95% of prescribed medication in the previous week prior to the study. Data were summarized using proportions, and chi2 test was used to explore associations between categorical variables. Predictors of adherence to HAART were determined by binary logistic regression. Level of significance was set at p < 0.05. RESULTS: The mean age of PLHIV who accessed treatment was 35.7 +/- 9.32 years. Females constituted 68.6% of all participants. The self reported adherence rate based on a one week recall prior to the study was 59.9%. The major reasons cited by respondents for skipping doses were operating a busy schedule, simply forgot medications, felt depressed, and travelling out of town. On logistic regression analysis, perceived improved health status [OR 3.11; CI: 1.58-6.11], reduced pill load [OR 1.25; 95% CI: 0.46-2.72] and non-use of herbal remedies [OR 1.83; 95% CI: 1.22-2.72] were the major predictors for adherence to HAART. However, payment for ART services significantly decreased the likelihood of adherence to HAART. [OR 0.46; 95% CI: 0.25-0.87.]. CONCLUSIONS: The adherence rate reported in this study was quite low. Appropriate adherence enhancing intervention strategies targeted at reducing pill load and ensuring an uninterrupted access to free services regimen is strongly recommended. PMID- 24229405 TI - Surface-enhanced Raman scattering of suspended monolayer graphene. AB - The interactions between phonons and electrons induced by the dopants or the substrate of graphene in spectroscopic investigation reveal a rich source of interesting physics. Raman spectra and surface-enhanced Raman spectra of supported and suspended monolayer graphenes were measured and analyzed systemically with different approaches. The weak Raman signals are greatly enhanced by the ability of surface-enhanced Raman spectroscopy which has attracted considerable interests. The technique is regarded as wonderful and useful tool, but the dopants that are produced by depositing metallic nanoparticles may affect the electron scattering processes of graphene. Therefore, the doping and substrate influences on graphene are also important issues to be investigated. In this work, the peak positions of G peak and 2D peak, the I2D/IG ratios, and enhancements of G and 2D bands with suspended and supported graphene flakes were measured and analyzed. The peak shifts of G and 2D bands between the Raman and SERS signals demonstrate the doping effect induced by silver nanoparticles by n-doping. The I2D/IG ratio can provide a more sensitive method to carry out the doping effect on the graphene surface than the peak shifts of G and 2D bands. The enhancements of 2D band of suspended and supported graphenes reached 138, and those of G band reached at least 169. Their good enhancements are helpful to measure the optical properties of graphene. The different substrates that covered the graphene surface with doping effect are more sensitive to the enhancements of G band with respect to 2D band. It provides us a new method to distinguish the substrate and doping effect on graphene. PACS: 78.67.Wj (optical properties of graphene); 74.25.nd (Raman and optical spectroscopy); 63.22.Rc (phonons in graphene). PMID- 24229406 TI - Inducement of cytokine release by GFPBW2, a novel polysaccharide from fruit bodies of Grifola frondosa , through dectin-1 in macrophages. AB - Polysaccharides, especially beta-glucans isolated from various species of mushrooms, are considered as biological response modifiers (BRMs) to be widely used in the treatment of cancer, especially due to their immunostimulatory activity. We herein characterized the structure of a novel water-soluble homogeneous polysaccharide (GFPBW2) from the fruit bodies of mushroom Grifola frondosa and investigated its immunomodulatory activity in vitro. GFPBW2 was purified from the alkali-extracted fractions by stepwise elution with a molecular weight of 26.2 kDa. On the basis of infrared and NMR spectroscopy, methylation and monosaccharide composition analysis, partial acid hydrolysis, and Smith degradation, its structure was elucidated to possess a backbone consisting of beta-d-1,3- and beta-d-1,4-linked glucopyranosyl residues, with branches attached to O-6 of beta-d-1,3-linked glucopyranosyl residues. Functionally, it is an effective inducer of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in murine resident peritoneal macrophages. Using quartz crystal microbalance (QCM) analysis, we found that GFPBW2 could bind dendritic cell associated C-type lectin-1 (Dectin-1) with an affinity constant (Kd) value of 1.08 * 10 (-7) M, while it could activate Syk and enhance TNF-alpha production in RAW264.7 cells overexpressing wild type but not mutant Dectin-1. Furthermore, Syk, NF-kappaB signaling, and cytokine release in resident peritoneal macrophages induced by GFPBW2 could be significantly inhibited by a specific Dectin-1 blocking reagent, Laminarin. These data suggested that GFPBW2 might be a potential ligand of Dectin-1, and the potential of GFPBW2 to activate macrophage through triggering cytokine secretion might be attributed, at least in part, to the involvement of Dectin-1. PMID- 24229407 TI - PECA: a novel statistical tool for deconvoluting time-dependent gene expression regulation. AB - Protein expression varies as a result of intricate regulation of synthesis and degradation of messenger RNAs (mRNA) and proteins. Studies of dynamic regulation typically rely on time-course data sets of mRNA and protein expression, yet there are no statistical methods that integrate these multiomics data and deconvolute individual regulatory processes of gene expression control underlying the observed concentration changes. To address this challenge, we developed Protein Expression Control Analysis (PECA), a method to quantitatively dissect protein expression variation into the contributions of mRNA synthesis/degradation and protein synthesis/degradation, termed RNA-level and protein-level regulation respectively. PECA computes the rate ratios of synthesis versus degradation as the statistical summary of expression control during a given time interval at each molecular level and computes the probability that the rate ratio changed between adjacent time intervals, indicating regulation change at the time point. Along with the associated false-discovery rates, PECA gives the complete description of dynamic expression control, that is, which proteins were up- or down-regulated at each molecular level and each time point. Using PECA, we analyzed two yeast data sets monitoring the cellular response to hyperosmotic and oxidative stress. The rate ratio profiles reported by PECA highlighted a large magnitude of RNA-level up-regulation of stress response genes in the early response and concordant protein-level regulation with time delay. However, the contributions of RNA- and protein-level regulation and their temporal patterns were different between the two data sets. We also observed several cases where protein-level regulation counterbalanced transcriptomic changes in the early stress response to maintain the stability of protein concentrations, suggesting that proteostasis is a proteome-wide phenomenon mediated by post-transcriptional regulation. PMID- 24229408 TI - SUNPLIN: simulation with uncertainty for phylogenetic investigations. AB - BACKGROUND: Phylogenetic comparative analyses usually rely on a single consensus phylogenetic tree in order to study evolutionary processes. However, most phylogenetic trees are incomplete with regard to species sampling, which may critically compromise analyses. Some approaches have been proposed to integrate non-molecular phylogenetic information into incomplete molecular phylogenies. An expanded tree approach consists of adding missing species to random locations within their clade. The information contained in the topology of the resulting expanded trees can be captured by the pairwise phylogenetic distance between species and stored in a matrix for further statistical analysis. Thus, the random expansion and processing of multiple phylogenetic trees can be used to estimate the phylogenetic uncertainty through a simulation procedure. Because of the computational burden required, unless this procedure is efficiently implemented, the analyses are of limited applicability. RESULTS: In this paper, we present efficient algorithms and implementations for randomly expanding and processing phylogenetic trees so that simulations involved in comparative phylogenetic analysis with uncertainty can be conducted in a reasonable time. We propose algorithms for both randomly expanding trees and calculating distance matrices. We made available the source code, which was written in the C++ language. The code may be used as a standalone program or as a shared object in the R system. The software can also be used as a web service through the link: http://purl.oclc.org/NET/sunplin/. CONCLUSION: We compare our implementations to similar solutions and show that significant performance gains can be obtained. Our results open up the possibility of accounting for phylogenetic uncertainty in evolutionary and ecological analyses of large datasets. PMID- 24229409 TI - Vermiculite's strong buffer capacity renders it unsuitable for studies of acidity on soybean (Glycine max L.) nodulation and growth. AB - BACKGROUND: Vermiculite is the most common soil-free growing substrate used for plants in horticultural and scientific studies due to its high water holding capacity. However, some studies are not suitable to be conducted in it. The described experiments aimed to test the suitability of vermiculite to study the effect of acidity on nodulation and growth of soybean (Glycine max L.). METHODS: Two different nutrient solutions (Broughton & Dilworth, and modified Herridge nutrient solutions) with or without MES buffer addition were used to irrigate soybean grown on vermiculite growth substrates. The pH of nutrient solutions was adjusted to either pH 4.0 or 7.0 prior its use. The nodulation and vegetative growth of soybean plants were assessed at 3 and 4 weeks after inoculation. RESULTS: The unsuitability of presumably inert vermiculite as a physical plant growth substrate for studying the effects of acidity on soybean nodulation and plant growth was illustrated. Nodulation and growth of soybean grown in vermiculite were not affected by irrigation with pH-adjusted nutrient solution either at pH 4.0 or 7.0. This was reasonably caused by the ability of vermiculite to neutralise (buffer) the pH of the supplied nutrient solution (pH 2.0-7.0). CONCLUSIONS: Due to its buffering capacity, vermiculite cannot be used as growth support to study the effect of acidity on nodulation and plant growth. PMID- 24229410 TI - Newborn screening for Hb H disease by determination of Hb Bart's using the Sebia capillary electrophoresis system in southern China. AB - Hb H (beta4) disease is an inherited hemoglobin (Hb) defect in which three of the four alpha-globin genes are deleted or dysfunctional. The clinical manifestations vary widely from mild asymptomatic anemia to a severely anemic state. Recent literature suggests that Hb H disease is not as benign a disorder as previously thought. Newborn screening for Hb H disease is especially appealing because the screening test is based on the detection of Hb Bart's (gamma4) that is only possible within the newborn period. In a 2-year period of newborn screening, 18 babies were found to have Hb H disease in a total of 9490 newborns. The overall prevalence for Hb H disease among all newborns in southern China is approximately 1 in 500. The correct diagnosis would allow affected infants to be properly cared for and reduce mortality rate. PMID- 24229411 TI - World AIDS Day: together we will stop HIV transmission and conquer AIDS. PMID- 24229413 TI - Odor naming and interpretation performance in 881 schizophrenia subjects: association with clinical parameters. AB - BACKGROUND: Olfactory function tests are sensitive tools for assessing sensory cognitive processing in schizophrenia. However, associations of central olfactory measures with clinical outcome parameters have not been simultaneously studied in large samples of schizophrenia patients. METHODS: In the framework of the comprehensive phenotyping of the GRAS (Gottingen Research Association for Schizophrenia) cohort, we modified and extended existing odor naming (active memory retrieval) and interpretation (attribute assignment) tasks to evaluate them in 881 schizophrenia patients and 102 healthy controls matched for age, gender and smoking behavior. Associations with emotional processing, neuropsychological test performance and disease outcome were studied. RESULTS: Schizophrenia patients underperformed controls in both olfactory tasks. Odor naming deficits were primarily associated with compromised cognition, interpretation deficits with positive symptom severity and general alertness. Contrasting schizophrenia extreme performers of odor interpretation (best versus worst percentile; N=88 each) and healthy individuals (N=102) underscores the obvious relationship between impaired odor interpretation and psychopathology, cognitive dysfunctioning, and emotional processing (all p<0.004). CONCLUSIONS: The strong association of performance in higher olfactory measures, odor naming and interpretation, with lead symptoms of schizophrenia and determinants of disease severity highlights their clinical and scientific significance. Based on the results obtained here in an exploratory fashion in a large patient sample, the development of an easy-to-use clinical test with improved psychometric properties may be encouraged. PMID- 24229414 TI - High admission glucose levels increase Fas apoptosis and mortality in patients with acute ST-elevation myocardial infarction: a prospective cohort study. AB - BACKGROUND: The presence of diabetes and plasma glucose concentration on admission are associated with adverse outcomes after an acute myocardial infarction (AMI), as high glucose can induce vascular endothelial cell apoptosis. This study explored the relative associations among admission plasma glucose level, soluble Fas (sFas) concentration, and long-term survival in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: This prospective cohort study include 83 patients with acute STEMI. Based on their admission plasma glucose levels (7.8 and 11.1 mmol/L as the limits for low and high levels, respectively), patients were allocated into one of three groups: normal glucose (n = 33), median glucose (n = 24), and high glucose (n = 26). The admission plasma level of sFas was measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Patients were followed up for an average of 89 +/- 20 months for all causes of death and cardiovascular death. RESULTS: sFas levels were significantly higher in the high glucose group compared to the normal glucose group (5.87 +/- 1.70 mmol/L vs. 3.07 +/- 0.93 mmol/L, respectively, P < 0.05). The sFas level was positively associated with the admission plasma glucose level. The correlation coefficient (R) was 0.747, and R2 was 0.559. Mortality was significantly higher in the high glucose group compared to the normal glucose group (19.2% vs. 3.0%, respectively, P < 0.05). CONCLUSIONS: In patients with acute STEMI, plasma glucose level was high on admission, and sFas apoptosis levels were increased. Long-term follow-up revealed that a high admission plasma glucose level was associated with higher mortality compared to a normal admission glucose level. PMID- 24229415 TI - Multistep DNA-templated synthesis using a universal template. AB - We report a DNA-templated synthesis method that allows construction of the entire DNA-encoded library with a single DNA template. Taking advantage of deoxyinosine's indiscriminate base-pairing property, we designed a "universal template" that is capable of directing chemical reactions with multiple reactant DNAs with different sequences. In combination with other design features including photocleavable linkers and direct encoding by the reactant DNA, we demonstrated the capabilities of the universal template in library synthesis, target selection, and hit decoding. Our method can be generally and straightforwardly applied to prepare a variety of chemically diverse DNA-encoded libraries. PMID- 24229416 TI - Development and evaluation of a crosswalk between the SF-36 physical functioning scale and Health Assessment Questionnaire disability index in rheumatoid arthritis. AB - BACKGROUND: The SF-36 physical functioning scale (PF-10) and the Health Assessment Questionnaire disability index (HAQ-DI) are the most frequently used instruments for measuring self-reported physical function in rheumatoid arthritis (RA). The objective of this study was to develop a crosswalk between scores on the PF-10 and HAQ-DI in RA. METHODS: Item response theory (IRT) methods were used to co-calibrate both scales using data from 1791 RA patients. The appropriateness of a Rasch-based crosswalk was evaluated by comparing it with crosswalks based on a two-parameter and a multi-dimensional IRT model. The accuracy of the final crosswalk was cross-validated using baseline (n = 532) and 6-month follow-up (n = 276) data from an independent cohort of early RA patients. RESULTS: The PF-10 and HAQ-DI adequately fit a unidimensional Rasch model. Both scales measured a wide range of functioning, although the HAQ-DI tended to better target lower levels of functioning. The Rasch-based crosswalk performed similarly to crosswalks based on the two-parameter and multidimensional IRT models. Agreement between predicted and observed scale scores in the cross-validation sample was acceptable for group level comparisons. The longitudinal validity in discriminating between disease response states was similar between observed and predicted scores. CONCLUSION: The crosswalk developed in this study allows for converting scores from one scale to the other and can be used for group-level analyses in patients with RA. PMID- 24229417 TI - Modulation of HIV-1-induced activation of plasmacytoid dendritic cells by 6 desfluoroquinolones. AB - Chronic activation of plasmacytoid dendritic cells (pDCs) is an important contributor to the immunopathogenesis of HIV infection. The quinolone derivative chloroquine (CQ) prevents endosomal acidification, required for toll-like receptor sensing of HIV by pDCs, and is currently under clinical trial as an immunotherapeutic approach. We tested three different 6-desfluoroquinolones (6 DFQs), structurally related to CQ and endowed with antiretroviral activity, for their ability to inhibit HIV-induced pDC activation and interferon (IFN)-alpha production in peripheral blood mononuclear cells (PBMCs) in vitro. PBMCs from six healthy donors were cultured overnight with aldrithiol-2 (AT-2)-inactivated HIV 1MN in the presence or absence of 6-DFQs or CQ. IFN-alpha production was measured by ELISA; pDC and monocyte activation was analyzed by flow cytometry. Incubation with HIV labeled with the fluorescent dye DyLight-488 (DL488) was used to test virus uptake by flow cytometry. We found that the 6-DFQs effectively inhibited HIV-induced IFN-alpha similar to CQ, but only 6-DFQs also inhibited the upregulation of the pDC activation marker CD83. Interestingly, HIV-induced expression of the costimulatory molecule CD80 and, to a lesser extent CD86, was further enhanced on pDCs by 6-DFQs, but not CQ. Conversely, 6-DFQs and CQ had similar inhibitory effects on HIV-induced monocyte activation, consistent with the primary mechanism being associated with IFN-alpha signaling. Finally, 6-DFQs interfered with HIV interaction with pDCs and monocytes, but not myeloid DCs. Our data indicate that 6-DFQs may interfere with pDC-mediated and IFN-alpha-dependent immunopathogenesis while supporting pDC differentiation into mature antigen presenting cells by favoring expression of costimulatory molecules. PMID- 24229418 TI - Meta-analysis of incidence of early lung toxicity in 3-dimensional conformal irradiation of breast carcinomas. AB - BACKGROUND: This meta-analysis aims to ascertain the significance of early lung toxicity with 3-Dimensional (3D) conformal irradiation for breast carcinomas and identify the sub-groups of patients with increased risk. METHODS: Electronic databases, reference sections of major oncological textbooks and identified studies were searched for synonyms of breast radiotherapy and radiation pneumonitis (RP). Major studies in thoracic irradiation were reviewed to identify factors frequently associated with RP. Meta-analysis for RP incidence estimation and odds ratio calculation were carried out. RESULTS: The overall incidence of Clinical and Radiological RP is 14% and 42% respectively. Ten studies were identified. Dose-volume Histogram (DVH) related dosimetric factors (Volume of lung receiving certain dose, Vdose and Mean lung Dose, MLD), supraclavicular fossa (SCF) irradiation and age are significantly associated with RP, but not sequential chemotherapy and concomitant use of Tamoxifen. A poorly powered study in IMN group contributed to the negative finding. Smoking has a trend towards protective effect against RP. CONCLUSION: Use of other modalities may be considered when Ipsilateral lung V20Gy > 30% or MLD > 15 Gy. Extra caution is needed in SCF and IMN irradiation as they are likely to influence these dosimetric parameters. PMID- 24229419 TI - Anticancer C,N-cycloplatinated(II) complexes containing fluorinated phosphine ligands: synthesis, structural characterization, and biological activity. AB - A series of potent C,N-cycloplatinated(II) phosphine antitumor complexes containing fluorous substituents in the cyclometalated or the ancillary phosphine ligands [Pt(C-N)(PR3)Cl] or both have been synthesized and characterized. The crystal structure of [Pt(dmba){P(C6H4CF3-p)3}Cl].2CH2Cl2 (dmba = dimethylaminomethyl)phenyl) has been established by X-ray diffraction. Values of IC50 of the new platinum complexes were calculated toward a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). Complexes containing P(C6H4CF3-p)3 as ancillary ligand (with a bulky and electronegative CF3 substituent in para position) were the most cytotoxic compounds in all the tested cancer cell lines. In some cases, the IC50 values were 16-fold smaller than that of cisplatin and 11-fold smaller than the non fluorous analogue [Pt(dmba)(PPh3)Cl]. On the other hand, very low resistance factors (RF) in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF ~ 1) for most of the new compounds. Analysis of cell cycle was done for the three more active compounds in A2780. They arrest cell growth in G0/G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. They are also good cathepsin B inhibitors (an enzyme implicated in a number of cancer related events). PMID- 24229421 TI - Composition of clusters and building blocks in amylopectins from maize mutants deficient in starch synthase III. AB - Branches in amylopectin are distributed along the backbone. Units of the branches are building blocks (smaller) and clusters (larger) based on the distance between branches. In this study, composition of clusters and building blocks of amylopectins from dull1 maize mutants deficient in starch synthase III (SSIII) with a common genetic background (W64A) were characterized and compared with the wild type. Clusters were produced from amylopectins by partial hydrolysis using alpha-amylase of Bacillus amyloliquefaciens and were subsequently treated with phosphorylase a and beta-amylase to produce phi,beta-limit dextrins. Clusters were further extensively hydrolyzed with the alpha-amylase to produce building blocks. Structures of clusters and building blocks were analyzed by diverse chromatographic techniques. The results showed that the dull1 mutation resulted in larger clusters with more singly branched building blocks. The average cluster contained ~5.4 blocks in dull1 mutants and ~4.2 blocks in the wild type. The results are compared with previous results from SSIII-deficient amo1 barley and suggest fundamental differences in the cluster structures. PMID- 24229422 TI - Single-port vasoview sympathectomy for palmar hyperhidrosis: a clinical update. AB - INTRODUCTION: Thoracic sympathectomy remains an effective method for treatment of palmar hyperhidrosis refractory to other conservative forms of management. The procedure has become more acceptable following the introduction of the minimally invasive technique using video-assisted thoracic surgery (VATS). More recently, single-port VATS has gained popularity as an alternative approach to performing sympathectomy. We report on our experience and early results of single-port bilateral VATS sympathectomy using the Vasoview((r)) (Maquet Inc., Rastatt, Germany) device at our institute. SUBJECTS AND METHODS: All patients who underwent VATS sympathectomy for primary palmar hyperhidrosis between June 2011 and March 2012 were recruited into this prospective study. Patients' demographics and intraoperative and postoperative outcomes were collected. Effectiveness of the procedure, postoperative pain, duration of hospital stay, and complications were also measured. RESULTS: Sixteen patients underwent Vasoview bilateral VATS sympathectomy for severe palmar hyperhidrosis. Mean age was 23.8 years (range, 17 36 years), and mean operative time to complete the bilateral procedure was 56 minutes (range, 42-81 minutes). The procedure was successfully completed in all patients without the need to enlarge the incision or convert. Postoperatively, there was no mortality and no residual palmar hyperhidrosis. Mean postoperative stay was 0.9 days (range, 0.7-1.9 days). The mean visual analog pain score at discharge was 1.8 (range, 1.2-3.4). CONCLUSIONS: Single-port Vasoview sympathectomy for treatment of severe palmar hyperhidrosis is technically feasible and safe with satisfactory immediate and early results. Intermediate and long-term follow-up is required to monitor recurrence or late complications. Future studies are warranted to compare Vasoview single-port and other minimal invasive VATS approaches. PMID- 24229420 TI - Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen. AB - BACKGROUND: HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. RESULTS: Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. CONCLUSIONS: Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I. PMID- 24229423 TI - Rendezvous technique for cholecystocholedochal lithiasis in octogenarians: is it as effective as in younger patients, or should endoscopic sphincterotomy followed by laparoscopic cholecystectomy be preferred? AB - BACKGROUND: The treatment of cholecystocholedochal lithiasis (CCL) requires cholecystectomy and common bile duct (CBD) clearance, which can be achieved surgically or with a combination of surgery and endoscopy. The latter includes a two-stage-approach-preoperative retrograde cholangiography (ERC) and sphincterotomy (ST) followed by delayed laparoscopic cholecystectomy (LC), or vice versa-or a one-stage-approach-the rendezvous technique (RVT), where ERC, ST, and LC are performed during the same procedure. No data on the use of RVT in octogenarians have been reported in the literature so far. The study aims to show whether the RVT is as effective in elderly as in younger patients. Moreover, results of RVT are compared with those of a two-stage sequential treatment (TSST) in octogenarians, to identify the best approach to such a population. SUBJECTS AND METHODS: Prospectively collected data of 131 consecutive patients undergoing RVT for biliary tract stone disease were retrospectively analyzed. Two analyses were performed: (1) results of RVT (operative time, conversion rate, CBD clearance, morbidity/mortality, hospital stay, costs, and need for further endoscopy) were compared between octogenarians and younger patients, and (2) results of RVT in the elderly were compared with those of 27 octogenarians undergoing TSST for CCL. RESULTS: Octogenarians undergoing RVT were in poorer general condition (P<.0001) and had a higher conversion rate (P<.0001) and a longer hospital stay (P<.007) than younger patients. No differences in the rates of CBD clearance, surgery-related morbidity, mortality, and costs were recorded. Although octogenarians undergoing RVT were in poorer general condition than those undergoing TSST, the results of the two approaches were similar. CONCLUSIONS: RVT in the elderly seems to be as cost-effective as in younger patients; nevertheless, it may lead to a higher conversion rate and longer hospital stay. In octogenarians, RVT is not inferior to TSST in the treatment of CCL even for patients in poor condition. PMID- 24229424 TI - Temperature dependence of electrical characteristics of Pt/GaN Schottky diode fabricated by UHV e-beam evaporation. AB - Temperature-dependent electrical characterization of Pt/n-GaN Schottky barrier diodes prepared by ultra high vacuum evaporation has been done. Analysis has been made to determine the origin of the anomalous temperature dependence of the Schottky barrier height, the ideality factor, and the Richardson constant calculated from the I-V-T characteristics. Variable-temperature Hall effect measurements have been carried out to understand charge transport at low temperature. The modified activation energy plot from the barrier inhomogeneity model has given the value of 32.2 A/(cm2 K2) for the Richardson constant A** in the temperature range 200 to 380 K which is close to the known value of 26.4A/(cm2 K2) for n-type GaN. PMID- 24229425 TI - Investigation of serum protein profiles in scrapie infected sheep by means of SELDI-TOF-MS and multivariate data analysis. AB - BACKGROUND: Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrPC to PrPSc. Much is known about genetic susceptibility, uptake and dissemination of PrPSc in the body, but many aspects of prion diseases are still unknown. Different proteomic techniques have been used during the last decade to investigate differences in protein profiles between affected animals and healthy controls. We have investigated the protein profiles in serum of sheep with scrapie and healthy controls by SELDI-TOF-MS and LC-MS/MS. Latent Variable methods such as Principal Component Analysis, Partial Least Squares-Discriminant Analysis and Target Projection methods were used to describe the MS data. RESULTS: The serum proteomic profiles showed variable differences between the groups both throughout the incubation period and at the clinical end stage of scrapie. At the end stage, the target projection model separated the two groups with a sensitivity of 97.8%, and serum amyloid A was identified as one of the protein peaks that differed significantly between the groups. CONCLUSIONS: At the clinical end stage of classical scrapie, ten SELDI peaks significantly discriminated the scrapie group from the healthy controls. During the non-clinical incubation period, individual SELDI peaks were differently expressed between the groups at different time points. Investigations of differences in -omic profiles can contribute to new insights into the underlying disease processes and pathways, and advance our understanding of prion diseases, but comparison and validation across laboratories is difficult and challenging. PMID- 24229426 TI - Resistance to treatment in eating disorders: a critical challenge. AB - The Special Issue "Treatment resistance in Eating Disorders" gathers together the contributions provided by several experienced groups of researchers in the field of Eating Disorders (EDs). The main topic is addressed from multiple perspectives ranging from pathogenesis (including developmental and maintaining factors) to treatment. An explicative model of resistance in EDs is also proposed. PMID- 24229427 TI - Discussion of First-Degree Relatives' Colorectal Cancer Risk: Survivors' Perspectives. AB - Although screening reduces colorectal cancer (CRC) incidence and mortality, screening rates are low, particularly among CRC patients' first-degree relatives (FDRs). Little is known about discussion of family members' risk of CRC among patients and their health care providers or with their FDRs. The purpose of this research, guided by the Protection Motivation Theory, was to assess patients' patterns of disclosure of CRC diagnosis to adult siblings and/or children and discussion of familial risk by healthcare providers. A cross-sectional sample of patients who received care at a comprehensive cancer center was recruited to complete telephone-based interviews related to disclosure of CRC diagnosis to FDRs, recall of physician counseling about familial risk, and patients' perception of CRC risk to FDRs. Sixty-nine patients completed the interview. Most participants (n = 67, 97%) had informed their adult children or siblings of their CRC diagnosis to keep their family informed of their health status (n = 15, 22%) and to encourage FDRs to screen for CRC (n = 14, 20%). More than half of the participants' physicians (n = 38, 55%) discussed FDRs' risk of developing CRC with the patient. However, a substantial proportion of patients reported no physician discussion of this risk (n = 28, 41%). Data from this study may guide the development of interventions to facilitate physician discussion and counseling of CRC patients about their FDRs' risk for CRC. However, future studies should explore whether FDRs are likely to be screened after becoming aware of their family member's diagnosis of CRC. PMID- 24229428 TI - Pavane for a pulse pressure variation defunct. AB - Hemodynamic management of critically ill patients in the ICU or high-risk patients in the operating room has paradoxically shown progress in terms of outcome after the systematic application of volume responsiveness/flow optimization based on pulse pressure variation and/or stroke volume variation during controlled, positive-pressure ventilation in patients without spontaneous respiratory efforts. This assessment of circulatory optimization should ideally be based on an exhaustive, predictive and coherent physiological understanding of the cardiovascular system model. This paper sketches the extremely complex physiological background of the concept of volume responsiveness, concluding that it is not a reliable means of guiding hemodynamic optimization because it is based on a nonexhaustive, nonpredictive and incoherent physiological model. PMID- 24229429 TI - A self-expanding thermolabile nitinol stent as a minimally invasive treatment alternative for ureteral strictures in renal transplant patients. AB - BACKGROUND AND PURPOSE: Ureteral obstruction in renal transplant allografts secondary to strictures can pose a challenging problem. Its incidence is reported between 0.5% and 4.7%. Usually, open surgical repair is performed. We present a series of patients in whom a metal MemokathTM 051 stent has been used as a minimally invasive treatment alternative. METHODS: We analyzed our data on the use of thermo-expandable metallic Memokath 051 stents for ureteral strictures in renal transplant patients. RESULTS: Between 2003 and 2010, eight male kidney recipients with a mean age of 49 years and obstructed ureters after kidney transplantation were treated with ureteral Memokath insertion. In six patients, the obstruction was at the level of the anastomosis, and in two, at the pelviureteral junction. After a mean follow-up of 4 years, half of the stents are in situ providing a good graft function. The average indwelling time is 4 years. Spontaneous resolution of the stricture without the need for further stent insertion was seen in three patients after a mean indwelling time of 7.3 months. There was one treatment failure in a patient with an obstructed, dilated, and convoluted ureter that was unable to withhold the stent in situ. No perioperative complications were recorded in this series. The overall success rate was 87%. CONCLUSION: Ureteral stent placement with the Memokath 051 is a safe minimally invasive treatment alternative for ureteral strictures in renal transplant recipients. PMID- 24229430 TI - Successful nasal intubation with a laryngeal nerve monitoring tube using bronchoscopy in a patient with plunging goiter: a case report. AB - BACKGROUND: The appropriate positioning of nerve integrity monitoring during thyroid surgery is of relevance. In this case report we describe our experience with accurate placement of a nerve integrity monitoring endotracheal tube, obtained by fiberoptic control, in a patient with expected difficult airway management. CASE PRESENTATION: We report the case of a 70-year-old obese woman scheduled for elective total thyroidectomy due to plunging intrathoracic goiter. The preoperative indirect laryngoscopy pointed out a massive bombe of the hypopharyngeal wall to the right and right vocal cord paralysis. The epiglottis was oedematous and the glottis could not be identified. On physical examination, the tongue was large and a Mallampati's score of 3 was determined. Hence, due to an expected difficult airway management, a nasal intubation with an electromyographic nerve integrity monitoring endotracheal tube trough fiberoptic bronchoscopy was successfully performed. CONCLUSION: Our experience suggests that nasal intubation can be safely performed by using a nerve integrity monitoring tube with the help of fiberoptic bronchoscopy. PMID- 24229431 TI - Gene expression profiling analysis of hepatocellular carcinoma. AB - BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well understood, and the prognosis for patients with HCC remains very poor. METHODS: To disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method. RESULTS: In this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy. CONCLUSIONS: The study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients. PMID- 24229434 TI - Extraperitoneal laparoscopic adenomectomy (Madigan) versus bipolar transurethral resection of the prostate for benign prostatic hyperplasia greater than 80 ml: complications and functional outcomes after 3-year follow-up. AB - PURPOSE: To compare the performance of voluminous benign prostatic hyperplasia patients who have received laparoscopic simple prostatectomy (LSP) with the patients who have received bipolar transurethral resection of the prostate (B TURP) in their perioperative and 3-year follow-up period. METHODS: Ninety patients with prostate volumes >80 mL (range 80-130 mL) were randomly assigned to either LSP or B-TURP surgery type. The patients were followed up at 1, 3, 6, 12, 24, and 36 months postoperatively. Perioperative and follow-up characteristics were then recorded and compared. RESULTS: More blood loss, greater resected adenoma volume, and shorter catheterization duration were recorded in LSP group than that of B-TURP group (140.1+/-81.5 vs 93.1+/-54.0 mL; 65.3+/-13.8 vs 49.0+/ 12.7 mL; 3.3+/-1.2 vs 3.8+/-1.0 days; p<0.05). None of the patients in LSP group reported complications out of 30 days, while 1 case of urethral stricture, 36 cases of retrograde ejaculation, 1 case of bladder neck contracture, and 2 cases of recurrence were recorded in B-TURP group. At 1, 3, 6, and 12 months postoperatively, there were no significant differences in terms of postvoid residual urine volume, maximal urinary flow rate (Qmax), and International Prostate Symptom Score between the two groups (p>0.05). In contrast, the differences became significant at 24 and 36 months (p<0.05). CONCLUSIONS: Compared with B-TURP, LSP with Madigan technique is accompanied by less residual adenoma, shorter catheterization time, and more blood loss. Further, the risk of late complications is lower with LSP and, in terms of functional outcomes, LSP appears to be better than B-TURP beyond 2 years. PMID- 24229432 TI - Pathophysiology of endotoxin tolerance: mechanisms and clinical consequences. AB - Endotoxin tolerance was first described in a study that exposed animals to a sublethal dose of bacterial endotoxin. The animals subsequently survived a lethal injection of endotoxin. This refractory state is associated with the innate immune system and, in particular, with monocytes and macrophages, which act as the main participants. Several mechanisms are involved in the control of endotoxin tolerance; however, a full understanding of this phenomenon remains elusive. A number of recent reports indicate that clinical examples of endotoxin tolerance include not only sepsis but also diseases such as cystic fibrosis and acute coronary syndrome. In these pathologies, the risk of new infections correlates with a refractory state. This review integrates the molecular basis and clinical implications of endotoxin tolerance in various pathologies. PMID- 24229435 TI - Total knee arthroplasty treatment of rheumatoid arthritis with severe versus moderate flexion contracture. AB - BACKGROUND: This study aims to explore the technique of soft tissue balance and joint tension maintenance in total knee arthroplasty (TKA) for the rheumatoid arthritis (RA) patients with flexion contracture of the knee. METHODS: This retrospective study reviewed flexion contracture deformity of RA patients who underwent primary TKA and ligament and soft tissue balancing. Based on the flexion contracture deformity, the remaining 76 patients available for analysis were divided into two groups, i.e., severe flexion group (SF) and moderate flexion group (MF). RESULTS: There were no intraoperative complications in this study. All patients had improved Knee Society Rating System scores and range of motion. The flexion contracture was completely corrected in MF and SF patients. There were no cases of patellar dislocation, but three cases had mild mediolateral instability in severe flexion group. Four knees (two knees in SF versus two knees in MF) had transient peroneal nerve palsy but recovered after conservative therapy. CONCLUSIONS: TKA can be performed successfully in the RA knees with severe flexion contracture. It is very important in TKA to maintain the joint stability in the condition of severe flexion contracture deformity of the RA knee. PMID- 24229436 TI - Amino acid digestibility of heat damaged distillers dried grains with solubles fed to pigs. AB - The primary objective of this experiment was to determine the effects of heat treatment on the standardized ileal digestibility (SID) of amino acids (AA) in corn distillers dried grains with solubles (DDGS) fed to growing pigs. The second objective was to develop regression equations that may be used to predict the concentration of SID AA in corn DDGS. A source of corn DDGS was divided into 4 batches that were either not autoclaved or autoclaved at 130 degrees C for 10, 20, or 30 min. Four diets containing DDGS from each of the 4 batches were formulated with DDGS being the only source of AA and CP in the diets. A N-free diet also was formulated and used to determine the basal endogenous losses of CP and AA. Ten growing pigs (initial BW: 53.5 +/- 3.9 kg) were surgically equipped with a T-cannula in the distal ileum and allotted to a replicated 5 * 4 Youden square design with 5 diets and 4 periods in each square. The SID of CP decreased linearly (P < 0.05) from 77.9% in non-autoclaved DDGS to 72.1, 66.1, and 68.5% in the DDGS samples that were autoclaved for 10, 20, or 30 min, respectively. The SID of lysine was quadratically reduced (P < 0.05) from 66.8% in the non autoclaved DDGS to 54.9, 55.3, and 51.9% in the DDGS autoclaved for 10, 20, or 30 min, respectively. The concentrations of SID Arginine, Histidine, Leucine, Lysine, Methionine, Phenylalanine, or Threonine may be best predicted by equations that include the concentration of acid detergent insoluble N in the model (r2 = 0.76, 0.68, 0.67, 0.84, 0.76, 0.73, or 0.54, respectively). The concentrations of SID Isoleucine and Valine were predicted (r2 = 0.58 and 0.54, respectively) by the Lysine:CP ratio, whereas the concentration of SID Tryptophan was predicted (r2 = 0.70) by the analyzed concentration of Tryptophan in DDGS. In conclusion, the SID of AA is decreased as a result of heat damage and the concentration of SID AA in heat-damaged DDGS may be predicted by regression equations developed in this experiment. PMID- 24229437 TI - Existing trial data do not support that hydroxyethyl starch is less harmful when given on more 'correct' indications. PMID- 24229438 TI - Urine biochemistry in acute kidney injury: are we moving in the right direction? PMID- 24229439 TI - Patient related outcomes in a real life prospective follow up study: Allergen immunotherapy increase quality of life and reduce sick days. AB - BACKGROUND: One fourth of the adult population in Europe suffer from respiratory allergy. Subcutaneous-allergen-specific-immunotherapy (SCIT) has long-term disease modifying effect on disease specific Health-Related Quality of Life (HRQoL). The purpose of this study was to assess the effect of SCIT on alternative disease outcomes in patients with grass-pollen and/or house dust mite induced allergic rhino-conjunctivitis and/or an asthma diagnosis. Focus was on expressing outcomes in terms of generic quality of life (Quality-Adjusted-Life Years (QALY)) and reductions in sick days. METHODS: The study was a multi-centre study with prospective follow-up. 248 patients were initiated on SCIT. The disease specific Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ) and two generic (HRQoL) instruments 15D and EQ-5D were used at baseline and at follow up. The outcome measures included change in; disease severity, RQLQ-scores, number of days with symptoms- and number of sick days per year and finally changes in generic HRQoL and thus, QALY. Disease severity was assessed by specialist doctors; severity of rhino-conjunctivitis was classified according to the Allergic Rhinitis and its Impact on Asthma (ARIA) and asthma severity according to the Global Initiative for Asthma (GINA guideline). The remaining outcome measures were assessed by the patients in questionnaires at baseline and at follow-up. An intension to treat approach was applied. For missing items imputation of sample mean base-line values or follow-up values were used after specified criteria. The effect of SCIT on rhino-conjunctivitis and/or asthma diagnoses was analysed at follow-up using three logistic regression models. RESULTS: The disease severity showed significantly improved disease control. Mean RQLQ-score was reduced from 3.02 at baseline to 2.00 at follow-up. Average annual days with symptoms were reduced from 189 to 145 days whilst annual sick days were reduced from 3.7 to 1.2 days. The 15D-score increased from 0.83 to 0.86 and the EQ-5D-score from 0.70 to 0.77, which indicated an annual gain per patient of 0.03 0.06 QALY. CONCLUSIONS: Allergic patients suffering from rhino-conjunctivitis alone or rhino-conjunctivitis and asthma experience significantly increased HRQoL and they gain 0.03-0.06 QALY, when treated with SCIT for one year. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier: NCT01486498. PMID- 24229440 TI - Making the GRADE: how useful are the new Surviving Sepsis Campaign guidelines? PMID- 24229441 TI - High prevalence of human cytomegalovirus in carotid atherosclerotic plaques obtained from Russian patients undergoing carotid endarterectomy. AB - BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with cardiovascular disease (CVD) but the role of this virus in CVD progression remains unclear. We aimed to examine the HCMV serostatus in Russian patients (n = 90) who had undergone carotid endarterectomy (CEA) and controls (n = 82) as well as to determine the prevalence of HCMV immediate early (IE) and late (LA) antigens in carotid atherosclerotic plaques obtained from 89 patients. In addition, we sought to determine whether HCMV infection was associated with inflammatory activity in the plaque by quantifying infiltrating CD3 and CD68 positive cells and 5-LO immunoreactivity. METHODS: HCMV serology was assessed with ELISA and immunohistochemistry staining was performed to detect HCMV antigens, CD3, CD68 and 5-LO reactivity. The Fisher's exact test was used to compare i) seroprevalence of HCMV IgG between patients and controls and ii) HCMV positive or -negative to that of CD3, CD68 and 5-LO immunoreactive cells in plaque samples. The student-t test was performed to connote the significance level of mean optical density between patients and controls. RESULTS: The seroprevalence for HCMV IgG was high in both patients and controls (99% and 98%, respectively). Controls had significantly higher IgG titers for HCMV compared with patients (p = 0.0148). Strikingly, we found a high prevalence of HCMV antigens in atherosclerotic plaques; 57/89 (64%) and 47/87 (54%) were HCMV IE and LA positive, respectively. Most plaques had rather low HCMV reactivity with distinct areas of HCMV-positive cells mainly detected in shoulder regions of the plaques, but also in the area adjacent to the necrotic core and fibrous cap. In plaques, the cellular targets for HCMV infection appeared to be mainly macrophages/foam cells and smooth muscle cells. HCMV-positive plaques trended to be associated with increased numbers of CD68 positive macrophages and CD3 positive T cells, while 5-LO reactivity was high in both HCMV-positive and HCMV negative plaques. CONCLUSIONS: In Russian patients undergoing CEA, HCMV proteins are abundantly expressed in carotid plaques and may contribute to the inflammatory response in plaques via enhanced infiltration of CD68 and CD3 cells. PMID- 24229442 TI - Review of economic evidence in the prevention and early detection of colorectal cancer. AB - This paper aims to systematically review the cost-effectiveness evidence, and to provide a critical appraisal of the methods used in the model-based economic evaluation of CRC screening and subsequent surveillance. A search strategy was developed to capture relevant evidence published 1999-November 2012. Databases searched were MEDLINE, EMBASE, National Health Service Economic Evaluation (NHS EED), EconLit, and HTA. Full economic evaluations that considered costs and health outcomes of relevant intervention were included. Sixty-eight studies which used either cohort simulation or individual-level simulation were included. Follow-up strategies were mostly embedded in the screening model. Approximately 195 comparisons were made across different modalities; however, strategies modelled were often simplified due to insufficient evidence and comparators chosen insufficiently reflected current practice/recommendations. Studies used up to-date evidence on the diagnostic test performance combined with outdated information on CRC treatments. Quality of life relating to follow-up surveillance is rare. Quality of life relating to CRC disease states was largely taken from a single study. Some studies omitted to say how identified adenomas or CRC were managed. Besides deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA) was undertaken in some studies, but the distributions used for PSA were rarely reported or justified. The cost-effectiveness of follow-up strategies among people with confirmed adenomas are warranted in aiding evidence-informed decision making in response to the rapidly evolving technologies and rising expectations. PMID- 24229443 TI - Implementing a successful data-management framework: the UK10K managed access model. AB - This paper outlines the history behind open access principles and describes the development of a managed access data-sharing process for the UK10K Project, currently Britain's largest genomic sequencing consortium (2010 to 2013). Funded by the Wellcome Trust, the purpose of UK10K was two-fold: to investigate how low frequency and rare genetic variants contribute to human disease, and to provide an enduring data resource for future research into human genetics. In this paper, we discuss the challenge of reconciling data-sharing principles with the practicalities of delivering a sequencing project of UK10K's scope and magnitude. We describe the development of a sustainable, easy-to-use managed access system that allowed rapid access to UK10K data, while protecting the interests of participants and data generators alike. Specifically, we focus in depth on the three key issues that emerge in the data pipeline: study recruitment, data release and data access. PMID- 24229444 TI - Contextual modulation of medial prefrontal cortex to neutral faces in anxious adolescents. AB - BACKGROUND: Although interpretation biases are well documented among youth with anxiety disorders, understanding of their neural correlates is limited. In particular, there has been little study of how anxious youth neurobiologically represent changing contextual cues that may trigger anxiety. This study examined neural responses during a task in which participants viewed neutral faces paired with experimentally manipulated contextual stimuli. METHODS: Participants (16 youth with a primary anxiety disorder diagnosis and 15 age- and gender-matched controls) passively viewed neutral faces that were paired with either neutral descriptive vignettes or with vignettes that were potentially anxiety provoking (for example, those that involved performance/social evaluation). RESULTS: The two groups were differentiated by their medial prefrontal cortex (mPFC) responses, such that context modulated mPFC activation in anxious youth while non anxious youth demonstrated no such differentiation. Counter to expectations, the performance/evaluation frames were not associated with amygdala reactivity for either group. CONCLUSIONS: The present investigation is among the first to identify how context modulates mPFC responding to neutral stimuli among anxious youth. It takes an important step toward understanding the neurobiological correlates underlying interpretation biases of neutral stimuli in this population. PMID- 24229445 TI - Do health economic evaluations using observational data provide reliable assessment of treatment effects? AB - Economic evaluation in modern health care systems is seen as a transparent scientific framework that can be used to advance progress towards improvements in population health at the best possible value. Despite the perceived superiority that trial-based studies have in terms of internal validity, economic evaluations often employ observational data. In this review, the interface between econometrics and economic evaluation is explored, with emphasis placed on highlighting methodological issues relating to the evaluation of cost effectiveness within a bivariate framework. Studies that satisfied the eligibility criteria exemplified the use of matching, regression analysis, propensity scores, instrumental variables, as well as difference-in-differences approaches. All studies were reviewed and critically appraised using a structured template. The findings suggest that although state-of-the-art econometric methods have the potential to provide evidence on the causal effects of clinical and policy interventions, their application in economic evaluation is subject to a number of limitations. These range from no credible assessment of key assumptions and scarce evidence regarding the relative performance of different methods, to lack of reporting of important study elements, such as a summary outcome measure and its associated sampling uncertainty. Further research is required to better understand the ways in which observational data should be analysed in the context of the economic evaluation framework. PMID- 24229446 TI - Is quality costly? Patient and hospital cost drivers in vascular surgery. AB - An increasing focus on hospital productivity has rendered a need for more thorough knowledge of cost drivers in hospitals, including a need for quantification of the impact of age, case-mix and other characteristics of patients, as well as establishment of the cost-quality relationship.The aim of this study is to identify cost drivers for vascular surgery in Danish hospitals with a specific view to quality of the treatment: Is higher quality associated with increased costs, when all other cost drivers are accounted for?We analyse cost drivers in a register-based study, using patient level data from three sources: The Vascular Register, the hospital cost database, and the National Patient Register with added DRG-information. The analysis follows a multilevel set-up, where cost drivers at patient level are analysed in a set of general linear regression models including complications and mortality as quality measures. At the hospital level of the analysis, we analyse deviations of observed costs from risk-adjusted costs and compare these to deviations of observed quality from risk-adjusted quality.We find, not surprisingly, that a number of patient characteristics, including case-mix and severity, have a major impact on treatment costs. At patient level, both complications and mortality are associated with increased costs. At hospital department level, results are not straightforward, but could indicate a U-shaped association.We conclude that the relation between costs and quality is not straightforward, at least not at department level. Our results indicate, albeit vaguely, a U-shaped relation between quality, in terms of fewer surgical complications than expected, and costs at department level, since our results suggest that increasing costs for vascular departments are associated with increased quality when costs are high and decreased quality when costs are low. For mortality however, we have not been able to establish a clear relation to costs. PMID- 24229447 TI - What is the clinical course of transient synovitis in children: a systematic review of the literature. AB - BACKGROUND: Transient synovitis of the hip (TS) is considered to be a self limiting disease in childhood. However, because the etiology is unclear and some cases precede Legg-Perthes' disease, data on follow-up are important. Our aim was to summarize the knowledge on the clinical course of TS in children. METHODS: The study design was a systematic review and a literature search was conducted in Medline and Embase. Studies describing short and/or long-term follow-up of TS in children were included. Case reports, reviews and studies describing traumatic hip pain were excluded. Study quality was scored and data extraction was performed. The main outcome measures were short-term and long-term clinical course, and recurrence of symptoms. RESULTS: A total of 25 studies were included of which 14 were of high quality. At two-week follow-up, almost all children with TS were symptom free. Those with symptoms persisting for over one month were more prone to develop other hip pathology, such as Legg-Perthes' disease. The recurrence rate of TS ranged from 0-26.3%. At long-term follow-up, 0-10% of the children diagnosed with TS developed Legg-Perthes' disease. Hip pain after intensive physical effort and limited range of motion of the hip at long-term follow-up was reported in 12-28% and in 0-18% of the children, respectively. CONCLUSIONS: The majority of the studies indicate that children with TS recover within two weeks; recurrence was seen in 0-26% of the cases. Children with TS should be followed at least six months to increase the likelihood of not missing Legg-Perthes' disease. PMID- 24229448 TI - The high cost of celiac disease in an Israeli Health Maintenance Organization. AB - BACKGROUND: The aim of this study was to identify costs in patients diagnosed with Celiac disease. METHODS: This retrospective case control study covered the period 2003-2006 and was conducted in a large Israeli Health Maintenance Organization insuring over two million members. Our cohort comprised 1,754 patients with Celiac disease with a control group of 15,040. Costs were aggregated according to main cost-branches and computed individually for each member. A linear step wise regression was performed with costs being the dependent variable and the independent variables; age, gender and the presence of celiac disease. Costs were compared with patients suffering from other chronic diseases. RESULTS: The total costs of the patients with celiac disease were significantly higher than that of the control group for hospital admission, medications, laboratory and imaging. Hospital admission rate was 7.98% as opposed to 7.1% for the control group (p = 0.06). When compared with other chronic illnesses, the costs of patients with celiac disease were similar to those of patients with diabetes and hypertension. CONCLUSIONS: Patients with Celiac disease utilize medical services more than the general population. This research suggests that the use of medical resources by patients with Celiac disease may be higher than previously thought. PMID- 24229449 TI - Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1. AB - BACKGROUND: Circulation of cerebrospinal fluid (CSF) through the ventricular system is driven by motile cilia on ependymal cells of the brain. Disturbed ciliary motility induces the formation of hydrocephalus, a pathological accumulation of CSF resulting in ventricle dilatation and increased intracranial pressure. The mechanism by which loss of motile cilia causes hydrocephalus has not been elucidated. The aim of this study was: (1) to provide a detailed account of the development of ciliation in the brain of the African clawed frog Xenopus laevis; and (2) to analyze the relevance of ependymal cilia motility for CSF circulation and brain ventricle morphogenesis in Xenopus. METHODS: Gene expression analysis of foxj1, the bona fide marker for motile cilia, was used to identify potentially ciliated regions in the developing central nervous system (CNS) of the tadpole. Scanning electron microscopy (SEM) was used to reveal the distribution of mono- and multiciliated cells during successive stages of brain morphogenesis, which was functionally assessed by bead injection and video microscopy of ventricular CSF flow. An antisense morpholino oligonucleotide (MO) mediated gene knock-down that targeted foxj1 in the CNS was applied to assess the role of motile cilia in the ventricles. RESULTS: RNA transcripts of foxj1 in the CNS were found from neurula stages onwards. Following neural tube closure, foxj1 expression was seen in distinct ventricular regions such as the zona limitans intrathalamica (ZLI), subcommissural organ (SCO), floor plate, choroid plexus (CP), and rhombomere boundaries. In all areas, expression of foxj1 preceded the outgrowth of monocilia and the subsequent switch to multiciliated ependymal cells. Cilia were absent in foxj1 morphants, causing impaired CSF flow and fourth ventricle hydrocephalus in tadpole-stage embryos. CONCLUSIONS: Motile ependymal cilia are important organelles in the Xenopus CNS, as they are essential for the circulation of CSF and maintenance of homeostatic fluid pressure. The Xenopus CNS ventricles might serve as a novel model system for the analysis of human ciliary genes whose deficiency cause hydrocephalus. PMID- 24229450 TI - Cost of illness studies on reproductive, maternal, newborn, and child health: a systematic literature review. AB - BACKGROUND: The term ?reproductive, maternal, newborn, and child health (RMNCH)? describes an integrated continuum of health states which is central to Millennium Development Goals 4 and 5. While the burden of mortality and morbidity associated with RMNCH is well known, knowledge is still limited about the economic burden of RMNCH. Concrete evidence of cost of illness (COI) of RMNCH may help policy makers in supporting investment in RMNCH. METHODS: A systematic literature search of COI studies was performed in electronic databases. The time frame for the analysis was January 1990 ? April 2011. The databases checked were Medline (Pubmed), Embase and ECONbase, EconLit, the Cumulative Index to Nursing and Allied Health (CINAHL), the National Bureau of Economic Research, the Latin American and Caribbean Literature on Health Sciences Database (LILACS), and Popline. Furthermore, we searched working papers and reference lists of selected articles. RESULTS: All the studies investigated address particular complications and issues of RMNCH, e.g., preterm birth, non-exclusive breastfeeding, and sexually transmitted diseases (STDs), but not RMNCH as an entire continuum. Most of the studies were conducted in high income countries, with limited data on low and middle income countries. The burden of disease is very high even for single complications. For example, the disease burden related to non-exclusive breastfeeding was given as 14.39 billion international dollars (ID) (2012, purchasing power parity) per year in the USA. Methodological differences in study design, costing approach, perspective of analysis, and time frame make it difficult to compare different studies. CONCLUSION: The continuum of RMNCH covers a large portion of the lifespan from birth through the reproductive age. From a methodological perspective, an ideal COI study would clearly describe the perspective of analysis and, hence, the cost items (direct or indirect), cost collection procedure, discounting, quality of data, time frame of analysis, related comorbidities, and robust sensitivity analysis for all the assumptions. Further research is needed to measure the economic impact of RMNCH, including identification of the most cost-effective policy and interventions for prevention, reduction, and elimination of the complications of RMNCH. PMID- 24229451 TI - Does overcrowding and health insurance type impact patient outcomes in emergency departments? AB - : We examine the impact of Emergency Department (ED) overcrowding on wait times and patient outcomes using a unique cross section of about 32,000 patients for an ED located in the Southwestern United States. We construct a measure of a patient's outcome and estimate the extent to which it is worsened by long waits in the ED. We find that waiting at an ED due to overcrowding tends to generate a negative outcome for all patients. We also find that this negative outcome is larger for those on Medicaid or who have no insurance and smaller for those with private insurance or Medicare. JEL CLASSIFICATION CODES: I12; I13. PMID- 24229453 TI - Simulation model for cost estimation of integrated care concepts of heart failure patients. AB - BACKGROUND: As a direct result of the population growing older the total number of chronic illnesses increases. The future expenditure for care of chronically ill patients is an ever-present challenge for the health care system. New solutions based on integrated care or the inclusion of telemedical systems in the treatment procedure can be essential for reducing the future financial burden. Therefore a detailed economic model was developed, which enables the comparison of health and cost outcomes for conventional medical care and different integrated care concepts in heart failure treatment. METHODS: F0r modelling, the discrete event technique was used. The model takes outpatient care as well as inpatient care into account to estimate the total occurring costs. It enables the treatment of patients by a physician, a specialist or a clinical ambulance for the simulation of the outpatient care. For inpatient care the model considers the total-costs of the hospitalization and rate of re-admission and furthermore the costs which occur because of special medical treatments or necessary stay at intensive care units. To rate the severity of symptoms patients can be classified using NYHA groups. To outline some of the potential model results, two scenarios have been simulated to compare both methods of care regarding overall costs. RESULTS: The developed simulation model allows comparing health and cost outcomes of different integrated care concepts for the treatment of heart failure patients. Additionally to the simulation of standard outpatient and inpatient care procedures in Austria the approach of a telemedical monitoring system for heart failure patients was implemented in this economic model. With the simulated scenarios it could be shown that under the given simulation parameters the telemedical system can lead to cost savings of up to 8% within the first three years. CONCLUSIONS: The developed model represents a comprehensive tool, which opens a wide field of possible simulation scenarios for the treatment of heart failure patients with special focus on overall cost estimations and reimbursement strategies. The simulated scenarios show that telemedical care has the potential of improved health outcomes and economic benefits. PMID- 24229452 TI - New mutations in flagellar motors identified by whole genome sequencing in Chlamydomonas. AB - BACKGROUND: The building of a cilium or flagellum requires molecular motors and associated proteins that allow the relocation of proteins from the cell body to the distal end and the return of proteins to the cell body in a process termed intraflagellar transport (IFT). IFT trains are carried out by kinesin and back to the cell body by dynein. METHODS: We used whole genome sequencing to identify the causative mutations for two temperature-sensitive flagellar assembly mutants in Chlamydomonas and validated the changes using reversion analysis. We examined the effect of these mutations on the localization of IFT81, an IFT complex B protein, the cytoplasmic dynein heavy chain (DHC1b), and the dynein light intermediate chain (D1bLIC). RESULTS: The strains, fla18 and fla24, have mutations in kinesin 2 and cytoplasmic dynein, respectively. The fla18 mutation alters the same glutamic acid (E24G) mutated in the fla10-14 allele (E24K). The fla18 strain loses flagella at 32?C more rapidly than the E24K allele but less rapidly than the fla10-1 allele. The fla18 mutant loses its flagella by detachment rather than by shortening. The fla24 mutation falls in cytoplasmic dynein and changes a completely conserved amino acid (L3243P) in an alpha helix in the AAA5 domain. The fla24 mutant loses its flagella by shortening within 6 hours at 32?C. DHC1b protein is reduced by 18-fold and D1bLIC is reduced by 16-fold at 21?C compared to wild-type cells. We identified two pseudorevertants (L3243S and L3243R), which remain flagellated at 32?C. Although fla24 cells assemble full-length flagella at 21?C, IFT81 protein localization is dramatically altered. Instead of localizing at the basal body and along the flagella, IFT81 is concentrated at the proximal end of the flagella. The pseudorevertants show wild-type IFT81 localization at 21?C, but proximal end localization of IFT81 at 32?C. CONCLUSIONS: The change in the AAA5 domain of the cytoplasmic dynein in fla24 may block the recycling of IFT trains after retrograde transport. It is clear that different alleles in the flagellar motors reveal different functions and roles. Multiple alleles will be important for understanding structure-function relationships. PMID- 24229454 TI - Accelerometry and salivary cortisol response during Air Force Special Tactics Officer selection. AB - BACKGROUND: Special Tactics Officer (STO) selection is conducted to select officers to enter the combat controller training pipeline. The aims were to determine physical activity patterns, estimate energy expenditure, and identify whether return and/or unsuccessful candidates demonstrated differences in cortisol responses compared to non-selected and/or first-time attendees. METHODS: Participants completed the STO selection, consisting of 5 days of physical and mental challenges. Participants were equipped with ActiCals(r), and saliva samples were collected throughout the STO selection. RESULTS: Average activity counts were 684 +/- 200 counts?min-1, with no group differences. Estimated energy expenditure was 4,105 +/- 451 kcal?day-1. Cortisol was elevated following extended physical training but returned to baseline during rest. Return candidates had significantly lower cortisol responses compared to first-timers, 0.43 +/- 0.06 MUg?dl-1 versus 0.76 +/- 0.18 MUg?dl-1, respectively, p < 0.05. CONCLUSIONS: An individual's salivary cortisol response to the stresses incurred during the STO selection has the potential to be incorporated into the entire picture of a candidate's performance and ability to handle stress. PMID- 24229456 TI - When the dust settles: what did we learn from the bexarotene discussion? AB - With 27 million people affected by Alzheimer's disease (AD), any proposal of a novel avenue for drug development is hot news. When Cramer and colleagues proposed last year that they could tackle AD pathology in an AD mouse model with bexarotene, a drug already in use in the clinic for other diseases, the news was covered worldwide by the popular press. Apolipoprotein E4 is the strongest genetic risk factor for AD and bexarotene appeared to exert spectacular effects on AD pathology when tested in APP/PS1 transgenic mice. One year later the slumbering discussion on the use of bexarotene in AD exploded in a flurry of papers. Four papers question the initial optimistic claims, while two others can only partially support the original work. We summarize here the available data and try to make sense out of the controversy. The major question is what we can learn from the experiments and what these studies imply for the further development of bexarotene in the clinic. PMID- 24229455 TI - Assessing the pharmacokinetic profile of the CamMedNP natural products database: an in silico approach. AB - BACKGROUND: Drug metabolism and pharmacokinetic (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. Computer-based methods are slowly gaining ground in this area and are often used as initial tools to eliminate compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of the discovery of a drug. RESULTS: In the present study, we present an in silico assessment of the DMPK profile of our recently published natural products database of 1,859 unique compounds derived from 224 species of medicinal plants from the Cameroonian forest. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination (ADME) of the compounds. This survey demonstrated that about 50% of the compounds within the Cameroonian medicinal plant and natural products (CamMedNP) database are compliant, having properties which fall within the range of ADME properties of >95% of currently known drugs, while >73% of the compounds have <=2 violations. Moreover, about 72% of the compounds within the corresponding 'drug-like' subset showed compliance. CONCLUSIONS: In addition to the previously verified levels of 'drug-likeness' and the diversity and the wide range of measured biological activities, the compounds in the CamMedNP database show interesting DMPK profiles and, hence, could represent an important starting point for hit/lead discovery from medicinal plants in Africa. PMID- 24229457 TI - Xtreme Everest 2: unlocking the secrets of the Sherpa phenotype? AB - Xtreme Everest 2 (XE2) was part of an ongoing programme of field, laboratory and clinical research focused on human responses to hypoxaemia that was conducted by the Caudwell Xtreme Everest Hypoxia Research Consortium. The aim of XE2 was to characterise acclimatisation to environmental hypoxia during a standardised ascent to high altitude in order to identify biomarkers of adaptation and maladaptation. Ultimately, this may lead to novel diagnostic and treatment strategies for the pathophysiological hypoxaemia and cellular hypoxia observed in critically ill patients. XE2 was unique in comparing participants drawn from two distinct populations: native ancestral high-altitude dwellers (Sherpas) and native lowlanders. Experiments to study the microcirculation, mitochondrial function and the effect that nitric oxide metabolism may exert upon them were focal to the scientific profile. In addition, the genetic and epigenetic (methylation and histone modification) basis of observed differences in phenotype was explored. The biological samples and phenotypic metadata already collected during XE2 will be analysed as an independent study. Data generated will also contribute to (and be compared with) the bioresource obtained from our previous observational high-altitude study, Caudwell Xtreme Everest (2007). PMID- 24229458 TI - Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers autoimmunity and clinical disease? AB - Rheumatoid arthritis, currently regarded as a complex multifactorial disease, was initially characterized as such at the turn of the 19th century. Ever since, multiple lines of investigation have attempted to elucidate the etiological factor(s) involved in disease incidence. Genes--including those risk alleles within HLA-DR4--have been implicated but are insufficient to explain the vast majority of cases. Several environmental factors, therefore, are being studied. Among them, the role of periodontal disease and Porphyromonas gingivalis in the pathogenesis of rheumatoid arthritis has attracted both clinical and bench interest given supportive epidemiologic and mechanistic data. PMID- 24229459 TI - The potential role of 'non-rheumatic' therapies in rheumatic disease. AB - The relationship between inflammation and insulin resistance is complex and not fully understood. Patients with rheumatoid arthritis are at increased risk of mortality from cardiovascular disease, which is known to be associated with insulin resistance. In the previous issue of Arthritis Research & Therapy, Ormseth and colleagues report the results of an 8-week trial of pioglitazone, an agent commonly used to treat type 2 diabetes mellitus, upon the DAS-28 (disease activity score using 28 joint counts). Modest improvements in the DAS-28 CRP (DAS 28 C-reactive protein) were shown, with no effect on DAS-28 ESR (DAS-28 erythrocyte sedimentation rate). Other variables that improved with pioglitazone were the CRP, IL-6, and patient-reported assessment of global health. The authors discuss the contribution of insulin resistance to the inflammation noted in rheumatoid arthritis. PMID- 24229460 TI - Career perspective: Peter D Wagner. AB - This perspective focuses on key career decisions, explaining the basis of those decisions. In so doing, it exemplifies the unexpected influences of serendipity and the interaction between serendipity and planned events in shaping the career of one individual. PMID- 24229461 TI - International hypoxia symposium XVIII: 26 February-02 March 2013. AB - The 18th International Hypoxia Symposia, Lake Louise, Alberta, Canada, February 26-March 02, 2013, covered molecular basis of hypoxic responses (e.g., hypoxia inducible factor, nitrite, nitrate, and hemoglobin) and integrative physiology (e.g., exercise physiology, cerebral blood flow responses, live-high train-low, and population genetics). Free communications and poster sessions covered scientific areas from controlled lab settings to field settings of high altitudes (Andes to Himalayas). PMID- 24229462 TI - Genome-wide expression profiles of subchondral bone in osteoarthritis. AB - INTRODUCTION: The aim of this study was to evaluate, for the first time, the differences in gene expression profiles of normal and osteoarthritic (OA) subchondral bone in human subjects. METHODS: Following histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by micro-computed tomography, we isolated total RNA from regions of interest from human OA (n = 20) and non-OA (n = 5) knee lateral tibial (LT) and medial tibial (MT) plateaus. A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from 9 OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples. RESULTS: A total of 972 differentially expressed genes were identified (fold change >= +/- 2, P <=0.05) between LT (minimal degeneration) and MT (significant degeneration) regions from OA samples; these data implicated 279 canonical pathways in IPA. The qRT-PCR data strongly confirmed the accuracy of microarray results (R2 = 0.58, P <0.0001). Novel pathways were identified in this study including Periostin (POSTN) and Leptin (LEP), which are implicated in bone remodeling by osteoblasts. CONCLUSIONS: To the best of our knowledge, this study represents the most comprehensive direct assessment to date of gene expression profiling in OA subchondral bone. This study provides insights that could contribute to the development of new biomarkers and therapeutic strategies for OA. PMID- 24229463 TI - Biodiversity research in the "big data" era: GigaScience and Pensoft work together to publish the most data-rich species description. AB - With the publication of the first eukaryotic species description, combining transcriptomic, DNA barcoding, and micro-CT imaging data, GigaScience and Pensoft demonstrate how classical taxonomic description of a new species can be enhanced by applying new generation molecular methods, and novel computing and imaging technologies. This 'holistic' approach in taxonomic description of a new species of cave-dwelling centipede is published in the Biodiversity Data Journal (BDJ), with coordinated data release in the GigaScience GigaDB database. PMID- 24229465 TI - Extravascular lung water in acute respiratory distress syndrome and the Berlin definition: time for real change. PMID- 24229464 TI - A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype. AB - INTRODUCTION: Breast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable to analyse the involvement of thousands of genes in the survival of cells with cancer stem cell properties. METHODS: We describe a sub-population expressing the stem-like marker CD44(+)/CD24(-/low) in SUM149 that were enriched in mammospheres. To identify genes functionally involved in the maintenance of the sub-population with cancer stem cell properties, we targeted over 5000 genes by RNAi and tested their ability to grow as mammospheres. The identified candidate ATG4A was validated in mammosphere and soft agar colony formation assays. Further, we evaluated the influence of ATG4A expression on the sub-population expressing the stem-like marker CD44(+)/CD24(low). Next, the tumorigenic potential of SUM149 after up- or down-regulation of ATG4A was examined by xenograft experiments. RESULTS: Using this method, Jak-STAT as well as cytokine signalling were identified to be involved in mammosphere formation. Furthermore, the autophagy regulator ATG4A was found to be essential for the maintenance of a sub-population with cancer stem cell properties and to regulate breast cancer cell tumourigenicity in vivo. CONCLUSION: In summary, we present a high-throughput screening system to identify genes involved in cancer stem cell maintenance and demonstrate its utility by means of ATG4A. PMID- 24229466 TI - A protocol guided by transpulmonary thermodilution and lactate levels for resuscitation of patients with severe burns. AB - Over-resuscitation is deleterious in many critically ill conditions, including major burns. For more than 15 years, several strategies to reduce fluid administration in burns during the initial resuscitation phase have been proposed, but no single or simple parameter has shown superiority. Fluid administration guided by invasive hemodynamic parameters usually resulted in over resuscitation. As reported in the previous issue of Critical Care, Sanchez Sanchez and colleagues analyzed the performance of a 'permissive hypovolemia' protocol guided by invasive hemodynamic parameters (PiCCO, Pulsion Medical Systems, Munich, Germany) and vital signs in a prospective cohort over a 3-year period. The authors' results confirm that resuscitation can be achieved with below-normal levels of preload but at the price of a fluid administration greater than predicted by the Parkland formula (2 to 4 mL/kg per% burn). The classic approach based on an adapted Parkland equation may still be the simplest until further studies identify the optimal bundle of resuscitation goals. PMID- 24229467 TI - Comparison of the metabolic responses to ingestion of hydrothermally processed high-amylopectin content maize, uncooked maize starch or dextrose in healthy individuals. AB - Optimal carbohydrate ingestion strategies as nutritional therapy for glycogen storage diseases have not been fully realised, in part, due to difficulties in accessing patient cohorts, alongside limited details on metabolic effects and insight into working mechanisms. The present pilot study compared glycaemic and fuel oxidation responses following the ingestion of a hydrothermally processed maize starch (HPMS), an uncooked maize starch (UCMS) and maize-derived dextrose (DEX) at rest and during and after exercise in healthy individuals. A total of eight participants (seven males and one female; body mass (BM) 76.9 (SEM 5.2) kg) visited the laboratory on three occasions. During each visit, the participants ingested 1 g/kg BM of HPMS (GlycosadeTM), UCMS (ArgoTM) or DEX as a 10% solution. Blood samples were collected over a 2 h rest period and for 2 h after a 60 min treadmill run at 65 (SEM 1) % VO(2max). Mean values with their standard errors were analysed using repeated-measures ANOVA. Blood glucose concentrations under the HPMS condition were significantly elevated from resting values at 90 min (P=0.02) after ingestion compared with those under the UCMS (60 min; P=0.02) and DEX (30 min; P=0.001) conditions. The rate of carbohydrate use during exercise after the ingestion of HPMS was 7-9% lower compared with that after the ingestion of either DEX or UCMS (P<0.05). The total amount of lipids oxidised during exercise was greater under the HPMS condition (26.2 (SEM 2.8) g) compared with that oxidised under the UCMS (19.6 (SEM 2.7) g; P=0.04) or DEX (20.6 (SEM 3.6) g; P=0.07) condition. The results demonstrated a glycaemic advantage to the ingestion of HPMS over that of UCMS or DEX. Carbohydrate oxidation was reduced after the ingestion of HPMS compared with that after the ingestion of UCMS or DEX, with a corresponding higher rate of endogenous lipid use during exercise. PMID- 24229469 TI - Physical activity in Alzheimer's disease: research in its infancy or why we need more randomized controlled trials. PMID- 24229468 TI - Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair. AB - The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application. PMID- 24229470 TI - Letter to the editor: low birth weight and adult depression: eliciting their association. PMID- 24229471 TI - Heterogeneity in development of adolescent anxiety disorder symptoms in an 8-year longitudinal community study. AB - In this study, we prospectively examined developmental trajectories of five anxiety disorder symptom dimensions (generalized anxiety disorder, panic disorder, school anxiety, separation anxiety disorder, and social anxiety disorder) from early to late adolescence in a community sample of 239 adolescents, assessed annually over 8 years. Latent growth modeling indicated different developmental trajectories from early into late adolescence for the different anxiety disorder symptoms, with some symptoms decreasing and other symptoms increasing over time. Sex differences in developmental trajectories were found for some symptoms, but not all. Furthermore, latent class growth analysis identified a normal developmental profile (including a majority of adolescents reporting persistent low anxiety disorder symptoms over 8 years) and an at-risk developmental profile (including a minority of adolescents reporting persistent high anxiety disorder symptoms over 8 years) for all of the anxiety disorder symptom dimensions except panic disorder. Additional analyses longitudinally supported the validity of these normal and at-risk developmental profiles and suggested differential associations between different anxiety disorder symptom dimensions and developmental trajectories of substance use, parenting, and identity development. Taken together, our results emphasize the importance of examining separate dimensions of anxiety disorder symptoms in contrast to a using a global, one-dimensional approach to anxiety. PMID- 24229472 TI - FIB plan and side view cross-sectional TEM sample preparation of nanostructures. AB - Focused ion beam is a powerful method for cross-sectional transmission electron microscope sample preparation due to being site specific and not limited to certain materials. It has, however, been difficult to apply to many nanostructured materials as they are prone to damage due to extending from the surface. Here we show methods for focused ion beam sample preparation for transmission electron microscopy analysis of such materials, demonstrated on GaAs GaInP core shell nanowires. We use polymer resin as support and protection and are able to produce cross-sections both perpendicular to and parallel with the substrate surface with minimal damage. Consequently, nanowires grown perpendicular to the substrates could be imaged both in plan and side view, including the nanowire-substrate interface in the latter case. Using the methods presented here we could analyze the faceting and homogeneity of hundreds of adjacent nanowires in a single lamella. PMID- 24229473 TI - Association between energy-dense food consumption at 2 years of age and diet quality at 4 years of age. AB - The present study aimed to evaluate the association between the consumption of energy-dense foods at 2 years of age and the consumption of foods and diet quality at 4 years of age. The sample included 705 children evaluated at 2 and 4 years of age, as part of the population-based birth cohort Generation XXI (Porto, Portugal). Data on sociodemographic and lifestyle factors of both children and mothers were collected by face-to-face interviews. The weight and height of children were measured by trained professionals. Based on FFQ, four energy-dense food groups were defined: soft drinks; sweets; cakes; salty snacks. A healthy eating index was developed using the WHO dietary recommendations for children (2006) aged 4 years. The associations were evaluated through Poisson regression models. After adjustment for maternal age and education, child's carer, child's siblings and child's BMI, higher consumption of energy-dense foods at 2 years of age was found to be associated with higher consumption of the same foods 2 years later. An inverse association was found between the intake (>= median) of soft drinks (incidence rate ratio (IRR) = 0.74, 95% CI 0.58, 0.95), salty snacks (IRR = 0.80, 95% CI 0.65, 1.00) and sweets (IRR = 0.73, 95% CI 0.58, 0.91) at 2 years of age and the consumption of fruit and vegetables at 4 years of age (>= 5 times/d). Weekly and daily consumption of energy-dense foods at 2 years of age was associated with a lower healthy eating score at 4 years of age (IRR = 0.75, 95% CI 0.58, 0.96; IRR = 0.56, 95% CI 0.41, 0.77, respectively). The consumption of energy-dense foods at young ages is negatively associated with the diet quality of children a few years later. PMID- 24229474 TI - Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging. AB - BACKGROUND: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. METHOD: Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. RESULTS: Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. CONCLUSIONS: Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed. PMID- 24229476 TI - The relationship between MAOA gene polymorphism and test anxiety. AB - In a sample of 569 Chinese high school students, the present findings indicated that students with the 4-repeat genotype showed a higher level of test anxiety. Furthermore, the prediction of academic performance on test anxiety was stronger among students with the 3-repeat genotype than those with the 4-repeat genotype. The present findings suggest that mono-amine-oxidase type A gene polymorphism is significantly related to test anxiety. PMID- 24229475 TI - Dietary and lifestyle characteristics associated with normal-weight obesity: the National FINRISK 2007 Study. AB - The aim of the present study was to compare the lifestyle (leisure-time physical activity, smoking habits and alcohol consumption) and dietary (energy-yielding nutrients, dietary fibre and foods) factors of Finns with a new syndrome called normal-weight obesity (NWO) with those of lean and overweight Finns. The representative population-based study included 4786 participants (25-74 years) from the National FINRISK 2007 Study with a health examination and questionnaires. Food intake was assessed using a validated FFQ. NWO was defined to include those with a normal BMI (<25 kg/m2) but excessive body fat (for men >=20 % and for women >=30 %) according to WHO definitions. The proportion of participants with a normal BMI was 28 % in men and 42 % in women. Of these, 34 % of the men and 45 % of the women had the NWO syndrome (among all the participants, 10 and 19 %, respectively). The waist circumference of the NWO participants was between that of the lean and overweight participants. Some potential risk factors, such as physical inactivity, (ex)-smoking and alcohol consumption, were related to NWO. In general, the intakes of energy-yielding nutrients were not associated with NWO. Instead, some healthy dietary factors (e.g. low intakes of meat and soft drinks) as well as unhealthy factors (e.g. low intakes of root vegetables, cereals and fish and high intake of confectionery) were related to NWO. The findings might explain why the NWO participants were of normal weight, but had an excessive body fat percentage. In conclusion, the proportion of normal-weight participants with an excessive body fat percentage was surprisingly high. The identification of NWO people may be of importance because although they appear lean, they have some unhealthy lifestyle and dietary habits related to obesity and overall health. PMID- 24229477 TI - The effect of magnesium ions on chromosome structure as observed by helium ion microscopy. AB - One of the few conclusions known about chromosome structure is that Mg2+ is required for the organization of chromosomes. Scanning electron microscopy is a powerful tool for studying chromosome morphology, but being nonconductive, chromosomes require metal/carbon coating that may conceal information about the detailed surface structure of the sample. Helium ion microscopy (HIM), which has recently been developed, does not require sample coating due to its charge compensation system. Here we investigated the structure of isolated human chromosomes under different Mg2+ concentrations by HIM. High-contrast and resolution images from uncoated samples obtained by HIM enabled investigation on the effects of Mg2+ on chromosome structure. Chromatin fiber information was obtained more clearly with uncoated than coated chromosomes. Our results suggest that both overall features and detailed structure of chromatin are significantly affected by different Mg2+ concentrations. Chromosomes were more condensed and a globular structure of chromatin with 30 nm diameter was visualized with 5 mM Mg2+ treatment, while 0 mM Mg2+ resulted in a less compact and more fibrous structure 11 nm in diameter. We conclude that HIM is a powerful tool for investigating chromosomes and other biological samples without requiring metal/carbon coating. PMID- 24229478 TI - There can be no moral obligation to eradicate all disability. PMID- 24229479 TI - Pre-operative renal volume predicts peak creatinine after congenital heart surgery in neonates. AB - OBJECTIVE: Acute kidney injury is common in neonates following surgery for congenital heart disease. We conducted a retrospective analysis to determine whether neonates with smaller pre-operative renal volume were more likely to develop post-operative acute kidney injury. DESIGN/SETTING: We conducted a retrospective review of 72 neonates who underwent congenital heart surgery for any lesion other than patent ductus arteriosus at our institution from January 2007 to December 2011. Renal volume was calculated by ultrasound using the prolate ellipsoid formula. The presence and severity of post-operative acute kidney injury was determined both by measuring the peak serum creatinine in the first 7 days post-operatively and by using the Acute Kidney Injury Network scoring system. RESULTS: Using a linear change point model, a threshold renal volume of 17 cm3 was identified. Below this threshold, there was an inverse linear relationship between renal volume and peak post-operative creatinine for all patients (p = 0.036) and the subgroup with a single morphologic right ventricle (p = 0.046). There was a non-significant trend towards more acute kidney injury using Acute Kidney Injury Network criteria in all neonates with renal volume <=17 cm3 (p = 0.11) and in the subgroup with a single morphologic right ventricle (p = 0.17). CONCLUSIONS: Pre-operative renal volume <=17 cm3 is associated with a higher peak post-operative creatinine and potentially greater risk for post-operative acute kidney injury for neonates undergoing congenital heart surgery. Neonates with a single right ventricle may be at higher risk. PMID- 24229480 TI - Anti-inflammatory effect of elemental diets with different fat composition in experimental colitis. AB - The aim of the present study was to evaluate the effectiveness of two isoenergetic elemental formulae with different fat content in the rat model of trinitrobenzene sulphonic acid (TNBS) colitis that mimics human inflammatory bowel disease. A total of forty-five male Wistar rats were assigned to five groups: (1) control group; (2) TNBS-induced colitis group; (3) TNBS-induced colitis group fed a long-chain TAG (LCT)-rich diet; (4) TNBS-induced colitis group fed a medium-chain TAG (MCT)-rich diet; (5) TNBS-induced colitis group fed a baseline diet and administered infliximab. Nutritional management lasted 12 d before and 4 d after rectal administration of TNBS. Subsequently, the rats were killed, and colonic tissue samples were collected for the assessment of histology, inflammation and oxidative stress. The MCT-rich diet decreased IL-6, IL-8 and intercellular adhesion molecule-1 (ICAM-1) levels and glutathione S transferase (GST) activity, while the LCT-rich diet reduced only ICAM-1 levels and GST activity (P<0.05). Neither elemental formula affected IL-10 levels. Infliximab reduced IL-8 and ICAM-1 levels and GST activity and increased IL-10 levels (P<0.05). No significant differences were detected in oxidative stress. Histological damage scores differed significantly only between the control and the TNBS-induced colitis group. A MCT-rich formula seems to exert stronger anti inflammatory effects than a LCT-rich formula in TNBS colitis. PMID- 24229481 TI - Psychodynamic therapy for adolescents suffering from co-morbid disorders of conduct and emotions in an in-patient setting: a randomized controlled trial. AB - BACKGROUND: Co-morbid disorders of conduct and emotions can be regarded as childhood antecedents of further negative developments (e.g. manifestation of personality disorders in adulthood). We evaluated a manualized psychodynamic therapy (PDT) for adolescents with these co-morbid disorders. METHOD: In a randomized controlled trial (RCT), 66 adolescents diagnosed with mixed disorders of conduct and emotions (F92 in ICD-10) were randomly assigned to a manualized in patient PDT group or a waiting list/treatment-as-usual (WL/TAU) control condition. Diagnoses according to DSM-IV were also documented. Patients were compared using rates of remission as the primary outcome. The Global Severity Index (GSI) and the Strengths and Difficulties Questionnaire (SDQ) were used as secondary measures. Assessments were performed at baseline, post-treatment and at the 6-month follow-up. RESULTS: The sample consisted of severely impaired adolescents with high rates of further co-morbid disorders and academic failure. Patients in the treatment group had a significantly higher rate of remission [odds ratio (OR) 26.41, 95% confidence interval (CI) 6.42-108.55, p < 0.001]. Compared with the control group, the PDT group resulted in significantly better outcomes on the SDQ (p = 0.04) but not the GSI (p = 0.18), with small between group effect sizes (SDQ: d = 0.38, GSI: d = 0.18). However, the scores of patients treated with PDT were post-treatment no longer significantly different from normative data on the GSI and within the normal range on the SDQ. The effects in the treatment group were stable at follow-up. Furthermore, most patients were reintegrated into educational processes. CONCLUSION: PDT led to remarkable improvement and furthered necessary preconditions for long-term stabilization. In future, PDT should be compared to other strong active treatments. PMID- 24229482 TI - Reading trust between the lines. "Housekeeping work" and inequality in human subjects review. PMID- 24229483 TI - Methamphetamine addiction and medical futility. PMID- 24229484 TI - Commentary: In the interest of fairness. PMID- 24229485 TI - Commentary: Withholding treatment from a drug addict: poor prognosis or just deserts? PMID- 24229486 TI - Commentary: Ethics and medical judgment: whose values? What process? PMID- 24229487 TI - What actually happened. PMID- 24229489 TI - Teaching about twins: college courses and public lectures. AB - The present article describes teaching experiences and observations in college courses and public lectures on twins. It is concluded that much more information about twins, at both research and practical levels, requires general dissemination. This discussion is followed by reviews of recent twin research on the topics of obesity control, post-zygotic mutation, in vitro fertilization, and schisis-associated defects. Media reports of twins accused of rape, infant Chinese twins sold separately for profit, a twin CEO, and twins pursuing the same career are presented. PMID- 24229490 TI - The need for a comprehensive molecular characterization of autism spectrum disorders. AB - Autism spectrum disorders (ASD) are a heterogeneous group of disorders which have complex behavioural phenotypes. Although ASD is a highly heritable neuropsychiatric disorder, genetic research alone has not provided a profound understanding of the underlying causes. Recent developments using biochemical tools such as transcriptomics, proteomics and cellular models, will pave the way to gain new insights into the underlying pathological pathways. This review addresses the state-of-the-art in the search for molecular biomarkers for ASD. In particular, the most important findings in the biochemical field are highlighted and the need for establishing streamlined interaction between behavioural studies, genetics and proteomics is stressed. Eventually, these approaches will lead to suitable translational ASD models and, therefore, a better disease understanding which may facilitate novel drug discovery efforts in this challenging field. PMID- 24229491 TI - Screening of congenital heart disease in the second trimester of pregnancy: current knowledge and new perspectives to the clinical practice. AB - OBJECTIVE: Congenital heart diseases are common in foetuses, with an incidence greater than six times that of chromosomal abnormalities; however, experts in cardiac anatomy have evaluated only the foetuses of pregnant women with increased risk for congenital heart disease. Over the years, it has become clear that congenital heart disease occur in foetuses of low-risk women. In the mid-1980s, a proposal to expand the assessment of cardiac anatomy was presented to obstetricians in order to improve prenatal screening. With the aim to systematise and improve the diagnosis of congenital heart disease in foetuses, the International Society of Ultrasound in Obstetrics and Gynecology established an ultrasound heart examination guideline. In this review, we have described the important features of this guideline and discussed the applications of this tool in clinical practice. METHODS: We performed a literature search of the National Library of Medicine for publications released between 2000 and 2012; we used search terms pertinent to congenital heart disease, such as foetal echocardiography, foetal heart and cardiac screening examination. RESULTS: The guidelines serve as a standard and help to systematise the screening for congenital heart diseases, but we think that some topics may be added to design the most appropriate screening method. However, we cannot expand the topics to be evaluated in this examination without good training of sonographers who undergo this screening. CONCLUSION: Although the screening standardisation is a good tool to be used in day-to-day practice, the increment of aortic and ductal archs and colour Doppler to heart screening could be useful to detect further cardiac defects. PMID- 24229492 TI - The case: a son's request to forego treatment. PMID- 24229493 TI - The acquisition of newly emerging sociophonetic variation: /str-/ in American English. AB - Eight children aged 4;1-8;1 and their primary caregivers participated in a study designed to evaluate their use of the onset cluster /str-/ in both read and conversational speech. The cluster is currently undergoing a reported sound change in many varieties of English, with the initial /s/ being retracted to [?]. The study compared the initial fricative of the cluster in both the children and their mothers. Acoustic analysis was carried out in order to categorize tokens as either [s] or [?] using spectral peak analysis. Results found that children as young as 5;1 were starting to exhibit the usage patterns of their mothers. The distribution of the novel variant suggests that the children may be learning this form via a process of lexical diffusion rather than by rule. Implications for the study of dialect acquisition and phonological acquisition in general are discussed. PMID- 24229494 TI - Reduced risk of dyslipidaemia with oolong tea consumption: a population-based study in southern China. AB - Experimental studies have suggested that tea consumption could lower the risk of dyslipidaemia. However, epidemiological evidence is limited, especially in southern China, where oolong tea is the most widely consumed beverage. We conducted a population-based case-control study to evaluate the association between consumption of tea, especially oolong tea, and risk of dyslipidaemia in Shantou, southern China, from 2010 to 2011. Information on tea consumption, lifestyle characteristics and food consumption frequency of 1651 patients with newly diagnosed dyslipidaemia and 1390 controls was obtained using a semi quantitative questionnaire. Anthropometric variables and serum biochemical indices were determined. Drinking more than 600 ml (2 paos) of green, oolong or black tea daily was found to be associated with the lowest odds of dyslipidaemia risk (P< 0.001) when compared with non-consumption, but only oolong tea consumption was found to be associated with low HDL-cholesterol levels. A dose response relationship between duration of tea consumption and risk of dyslipidaemia (OR 0.10, 95% CI 0.06, 0.16), as well as that between amount of dried tea leaves brewed and risk of dyslipidaemia (OR 0.34, 95% CI 0.24, 0.48), was found. Moreover, consumption of oolong tea for the longest duration was found to be associated with 3.22, 11.99 and 6.69% lower blood total cholesterol, TAG and LDL-cholesterol levels, respectively. In conclusion, the present study indicates that long-term oolong tea consumption may be associated with a lower risk of dyslipidaemia in the population of Shantou in southern China. PMID- 24229495 TI - Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder. AB - Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5 HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5 HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder. PMID- 24229496 TI - Effects of potassium chloride and potassium bicarbonate in the diet on urinary pH and mineral excretion of adult cats. AB - Low dietary K levels have been associated with increasing renal Ca excretion in humans, indicating a higher risk of calcium oxalate (CaOx) urolith formation. Therefore, the present study aimed to investigate whether dietary K also affects the urine composition of cats. A total of eight adult cats were fed diets containing 0.31 % native K and 0.50, 0.75 and 1.00 % K from KCl or KHCO3 and were evaluated for the effects of dietary K. High dietary K levels were found to elevate urinary K concentrations (P<0.001). Renal Ca excretion was higher in cats fed the KCl diets than in those fed the KHCO3 diets (P=0.026), while urinary oxalate concentrations were generally lower in cats fed the KCl diets and only dependent on dietary K levels in cats fed the KHCO3 diets (P<0.05). Fasting urine pH increased with higher dietary K levels (P=0.022), reaching values of 6.38 (1.00 % KCl) and 7.65 (1.00 % KHCO3). K retention was markedly negative after feeding the cats with the basal diet (-197 mg/d) and the 0.50 % KCl diet (-131 mg/d), while the cats tended to maintain their balance on being fed the highest KCl diet (-23.3 mg/d). In contrast, K from KHCO3 was more efficiently retained (P=0.018), with K retention being between -82.5 and 52.5 mg/d. In conclusion, the dietary inclusion of KHCO3 instead of KCl as K source could be beneficial for the prevention of CaOx urolith formation in cats, since there is an association between a lower renal Ca excretion and a generally higher urine pH. The utilisation of K is distinctly influenced by the K salt, which may be especially practically relevant when using diets with low K levels. PMID- 24229497 TI - The outcome of twin pregnancies discordant for trisomy 21. AB - The management of twin pregnancies discordant for trisomy 21 is dependent on the gestation at diagnosis, chorionicity, and parental preference. Our experience with the management of 15 cases in 1,839 twin pregnancies over a 12-year period is described. Selective termination is not always associated with a successful outcome for the normal co-twin. Two of the three monochorionic twin pregnancies affected by trisomy 21 were discordant. Amniocentesis should be strongly considered rather than chorionic villus sampling in monochorionic twin pregnancies. Pregnancies that continue with a trisomy 21 affected fetus are at risk of polyhydramnios and premature labor. PMID- 24229498 TI - Word order, referential expression, and case cues to the acquisition of transitive sentences in Italian. AB - In Study 1 we analyzed Italian child-directed-speech (CDS) and selected the three most frequent active transitive sentence frames used with overt subjects. In Study 2 we experimentally investigated how Italian-speaking children aged 2;6, 3;6, and 4;6 comprehended these orders with novel verbs when the cues of animacy, gender, and subject-verb agreement were neutralized. For each trial, children chose between two videos (e.g., horse acting on cat versus cat acting on horse), both involving the same action. The children aged 2;6 comprehended S + object pronoun + V (soprov) significantly better than S + V + object-noun (svonoun ). We explain this in terms of cue collaboration between a low cost cue (case) and the first argument = agent cue which we found to be reliable 76% of the time. The most difficult word order for all age groups was the object-pronoun + V + S (oprovs). We ascribe this difficulty to cue conflict between the two most frequent transitive frames found in CDS, namely V + object-noun and object pronoun + V. PMID- 24229499 TI - Protective effect of pranlukast on Abeta1-42-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1. AB - Deposition of extracellular amyloid-beta (Abeta) peptide is one of the pathological hallmarks of Alzheimer's disease (AD). Accumulation of Abeta is thought to associate with cognition deficits, neuroinflammation and apoptosis observed in AD. However, effective neuroprotective approaches against Abeta neurotoxicity are unavailable. In the present study, we analysed the effects of pranlukast, a selective cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, on the impairment of learning and memory formation induced by Abeta and the probable underlying electrophysiological and molecular mechanisms. We found that bilateral intrahippocampal injection of Abeta1-42 resulted in a significant decline of spatial learning and memory of mice in the Morris water maze (MWM) and Y-maze tests, together with a serious depression of in vivo hippocampal long-term potentiation (LTP) in the CA1 region of the mice. Importantly, this treatment caused significant increases in CysLT1R expression and subsequent NF-kappaB signaling, caspase-3 activation and Bcl-2 downregulation in the hippocampus or prefrontal cortex. Oral administration of pranlukast at 0.4 or 0.8 mg/kg for 4 wk significantly reversed Abeta1-42-induced impairments of cognitive function and hippocampal LTP in mice. Furthermore, pranlukast reversed Abeta1-42-induced CysLT1R upregulation, and markedly suppressed the Abeta1-42-triggered NF-kappaB pathway, caspase-3 activation and Bcl-2 downregulation in the hippocampus and prefrontal cortex in mice. Liquid chromatography-tandem mass spectrometry (LC MS/MS) assay confirmed its presence in the brain after oral administration of pranlukast in mice. These data disclose novel findings about the therapeutic potential of pranlukast, revealing a previously unknown therapeutic possibility to treat memory deficits associated with AD. PMID- 24229500 TI - Ants affect the infestation levels but not the parasitism of honeydew and non honeydew producing pests in citrus. AB - Ants act simultaneously as predators and as hemipteran mutualists, and thereby may affect the composition and population dynamics of a wide arthropod community. We conducted ant-exclusion experiments in order to determine the impact of ants on the infestation levels and parasitism of three of the most important citrus pests of western Mediterranean citrus: the honeydew producer Aleurothrixus floccosus Maskell (woolly whitefly) and the non-honeydew producers Aonidiella aurantii Maskell (California red scale; CRS) and Phyllocnistis citrella (Staiton) (citrus leafminer). The study was conducted in three commercial citrus orchards, each one dominated by one ant species (Pheidole pallidula, Lasius grandis or Linepithema humile) during two consecutive growing seasons (2011 and 2012). We registered a significant reduction of the CRS densities on fruits in the ant excluded treatment in the three orchards and in the two seasons, ranging from as high as 41% to as low as 21%. Similarly, the percentage of shoots occupied by A. floccosus was significantly lower in the ant-excluded plots in the orchards dominated by P. pallidula and L. humile. No significant differences were registered in the percentage of leaf surface loss caused by P. citrella between ant-allowed and ant-excluded treatments in any case. We found no significant differences in the percent parasitism between ant-allowed and ant-excluded treatments for honeydew and non-honeydew producing herbivores. These results suggest that: (i) ant management should be considered in order to reduce herbivore populations in citrus and (ii) mechanisms other than parasitism (e.g., predation) might explain the differences in herbivore infestation levels between treatments. PMID- 24229501 TI - Left atrial extension of hepatoblastoma via left superior pulmonary vein. AB - Hepatoblastoma is the most common malignant liver tumour in early childhood. The metastatic extension of hepatoblastoma into the left atrium via the pulmonary vein is rare. Reported lesions almost always involve a right-sided approach. Here we report the case of a 3-year-old girl with a recurrent hepatoblastoma at multiple sites, including the left atrium, brain, and lung. The patient was treated surgically for the prevention of further embolic complications and cardiac failure. PMID- 24229502 TI - Commentary: interpreting patient wishes. PMID- 24229504 TI - Mitral valve replacement in heavily calcified posterior annulus. PMID- 24229503 TI - Synthetic prostacyclin agonist, ONO1301, enhances endogenous myocardial repair in a hamster model of dilated cardiomyopathy: a promising regenerative therapy for the failing heart. AB - OBJECTIVES: Remodeling of the left ventricle (LV) in idiopathic dilated cardiomyopathy (IDCM) is known to be associated with multiple pathologic changes that endogenous factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), protect against. Although a clinically relevant delivery method of these factors has not been established, ONO1301, a synthetic prostacyclin agonist, has been shown to upregulate multiple cardioprotective factors, including HGF and VEGF, in vivo. We thus hypothesized that ONO1301 may reverse LV remodeling in the DCM heart. METHODS: ONO1301 dose-dependently added to the normal human dermal fibroblasts and human coronary artery smooth muscle cells in vitro, to measure the expression of HGF, VEGF, stromal cell-derived factor (SDF)-1, and granulocyte-colony stimulating factor (G-CSF), assessed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. delta-Sarcoglycan-deficient J2N-k hamsters, which is an established DCM model, were treated by epicardial implantation of an atelocollagen sheet with or without ONO1301 immersion or sham operation. RESULTS: ONO1301 dose-dependently upregulated expression of these 4 factors in vitro. ONO1301 treatment, which induced dominant elevation of ONO1301 levels for 2 weeks, significantly preserved cardiac performance and prolonged survival compared with the other groups. This treatment significantly upregulated expressions of cardioprotective factors and was associated with increased capillaries, attenuated fibrosis, and upregulation of alpha-sarcoglycan in the DCM heart. CONCLUSIONS: ONO1301 atelocollagen-sheet implantation reorganized cytoskeletal proteins, such as alpha-sarcoglycan, increased capillaries, reduced fibrosis, and was associated with upregulated expression of multiple cardioprotective factors, leading to preservation of cardiac performance and prolongation of survival in the delta-sarcoglycan deficient DCM hamster. PMID- 24229505 TI - Reply to the editor. PMID- 24229506 TI - Breast-fed infants and their later cardiovascular health: a prospective study from birth to age 32 years. AB - The aim of the present study was to evaluate the impact of infant breast-feeding on cardiovascular risk in young adults. This unique study group involved 158 subjects (eighty-two females) originally collected prospectively at birth in 1975 and followed up to the age of 32 years. Frequent visits during the first year guaranteed the knowledge of the precise duration of breast-feeding. All infants received at least some breast milk. Participants were assessed for both individual cardiovascular risk factors (blood pressure, plasma lipids, homeostatic model assessment of insulin resistance and waist circumference) and the general clinical risk of cardiovascular events by calculating the Framingham risk score (FRS) and the metabolic syndrome criteria score (NCEP-ATPIII; National Cholesterol Education Program's Adult Treatment Panel III). Data on lifestyle factors were carefully collected. Linear regression analyses revealed that the effect of the duration of breast-feeding was not relevant (0.02 decrease in the FRS per one additional breast-feeding month; 95 % CI - 0.19, 0.09). Similarly, the effect of breast-feeding was minor on all of the individual cardiovascular risk factors. We used sex, physical activity, dietary fat and vitamin C, smoking and alcohol consumption as covariates. Again, logistic regression analyses detected no significant impact of the duration of breast-feeding on the risk of the metabolic syndrome according to the NCEP-ATPIII (OR 0.95, 95 % CI 0.8, 1.1). The strongest independent predictor for later CVD risk was male sex. In conclusion, in this prospectively followed cohort of young adults born at term and at weight appropriate for gestational age, the duration of breast-feeding did not have an impact on the accumulation of cardiovascular risk factors. PMID- 24229507 TI - Fitness costs associated with field-evolved resistance to chlorantraniliprole in Plutella xylostella (Lepidoptera: Plutellidae). AB - Plutella xylostella (L.) is the most important pest of Brassicaceae worldwide, with a recent estimate of US$ 4-5 billion expenditure for the control of this insect. A case of very high resistance of this pest to chlorantraniliprole was recently associated with reduced efficacy in a Brazilian field of Brassica spp. Although diamide resistance has been characterized, the fitness of insects due to such resistance has yet to be examined. Therefore, in this study, biological parameters were assessed in both susceptible and resistant strains of P. xylostella subjected to sublethal chlorantraniliprole concentrations. The field strain showed high resistance to chlorantraniliprole (RR50=27,793-fold), although resistance rapidly decreased in the first generations, showing instability. The exposure of susceptible and resistant larvae to their respective LC1, LC10, and LC25 values led to an increased duration of the larval and pupae phases and reduced weight in both strains; however, no significant differences in pupal viability across the treatments were observed. The resistant insects presented significantly lower larval weight and fecundity and higher larval and pupal periods, hatchability, and male longevity when not exposed to chlorantraniliprole, suggesting a fitness cost associated with resistance. In addition, resistant females showed a significantly higher egg-laying period and longevity at LC25, whereas the males lived longer at LC1. Chlorantraniliprole negatively impacted the biological parameters of both strains tested, although these effects were more relevant to the resistant insects. Resistant P. xylostella showed negative and positive biological trade-offs when compared with the susceptible individuals in both the absence and presence of chlorantraniliprole. Despite the important role that these trade-offs may play in the evolution of resistance to chlorantraniliprole, practical applications still depend on such information as the dominance of fitness costs and resistance. PMID- 24229508 TI - Onset and temporal sequencing of lifetime anxiety, mood and substance use disorders in the general population. AB - Aims. To date, very few studies have examined the bi-directional associations between mood disorders (MDs), anxiety disorders (ADs) and substance use disorders (SUDs), simultaneously. The aims of the current study were to determine the rates and patterns of comorbidity of the common MDs, ADs and SUDs and describe the onset and temporal sequencing of these classes of disorder, by sex. Methods. Data came from the 2007 Australian National Survey of Mental Health and Wellbeing, a nationally representative household survey with 8841 (60% response rate) community residents aged 16-85. Results. Pre-existing mental disorders increase the risk of subsequent mental disorders in males and females regardless of the class of disorder. Pre-existing SUDs increase the risk of subsequent MDs and ADs differentially for males and females. Pre-existing MDs increase the risk of subsequent ADs differentially for males and females. Conclusions. Comorbidity remains a significant public health issue and current findings point to the potential need for sex-specific prevention and treatment responses. PMID- 24229509 TI - Commentary: the need for more questions. PMID- 24229510 TI - Regular exercise prevents non-cognitive disturbances in a rat model of Alzheimer's disease. AB - Previously, we reported that in a rat model of sporadic Alzheimer's disease (AD) generated by exogenous administration of Abeta1-42 (250 pmol/d for 2 wk) via mini osmotic pump, the animals exhibited learning and memory impairment, which could be attributed to the deleterious alterations in the levels of cognition-related signalling molecules. We showed that 4 wk of treadmill exercise totally prevented these impairments. Here, we evaluated the effect of exercise on non-cognitive function and basal synaptic transmission in the Cornu Ammonis 1 (CA1) area using the same AD model. Our results indicated that the anxiety behaviour of Abeta treated rats was prevented by 4 wk of treadmill exercise. Exercised/Abeta-infused rats spent a longer time in the centre area of the open field (OF), elevated plus maze (EPM) paradigms and the light area of the light-dark (LD) box, which were similar to those of control and exercise rats. Furthermore, under basal conditions the aberrant up-regulation of calcineurin (PP2B) and reduction of phosphorylated Ca2+/calmodulin dependent protein kinase II (p-CaMKII) levels induced by AD-like pathology were normalised by the exercise regimen. We conclude that regular exercise may exert beneficial effects on both cognitive and non cognitive functions in this AD model. PMID- 24229511 TI - Talking theory of mind talk: young school-aged children's everyday conversation and understanding of mind and emotion. AB - Links between young children's everyday use of mindful conversational skills and their success on laboratory tests of theory of mind understanding (ToM) were evaluated. Using published scales, teachers rated the conversational behavior and shyness of 129 children aged 60 to 101 months (M = 78.8 months) who were in their first years of primary school. The children also took batteries of first- and second-order false-belief tests along with tests of emotion understanding and general language ability. Correlational and regression analyses showed that performance on false-belief tests of ToM significantly predicted children's competence at reading others' minds in their everyday conversational interactions. Furthermore, these links transcended individual differences in language ability, shy personality, emotion understanding, and age. These findings augment and extend a growing body of evidence linking performance on laboratory ToM tests to socially competent real-world behavior. PMID- 24229512 TI - The Prehospital Sepsis Project: out-of-hospital physiologic predictors of sepsis outcomes. AB - INTRODUCTION: Severe sepsis and septic shock are common, expensive and often fatal medical problems. The care of the critically sick and injured often begins in the prehospital setting; there is limited data available related to predictors and interventions specific to sepsis in the prehospital arena. The objective of this study was to assess the predictive effect of physiologic elements commonly reported in the out-of-hospital setting in the outcomes of patients transported with sepsis. METHODS: This was a cross-sectional descriptive study. Data from the years 2004-2006 were collected. Adult cases (>=18 years of age) transported by Emergency Medical Services to a major academic center with the diagnosis of sepsis as defined by ICD-9-CM diagnostic codes were included. Descriptive statistics and standard deviations were used to present group characteristics. Chi-square was used for statistical significance and odds ratio (OR) to assess strength of association. Statistical significance was set at the .05 level. Physiologic variables studied included mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and shock index (SI). RESULTS: Sixty-three (63) patients were included. Outcome variables included a mean hospital length of stay (HLOS) of 13.75 days (SD = 9.97), mean ventilator days of 4.93 (SD = 7.87), in hospital mortality of 22 out of 63 (34.9%), and mean intensive care unit length of-stay (ICU-LOS) of 7.02 days (SD = 7.98). Although SI and RR were found to predict intensive care unit (ICU) admissions, [OR 5.96 (CI, 1.49-25.78; P = .003) and OR 4.81 (CI, 1.16-21.01; P = .0116), respectively] none of the studied variables were found to predict mortality (MAP <65 mmHg: P = .39; HR >90: P = .60; RR >20 P = .11; SI >0.7 P = .35). CONCLUSIONS: This study demonstrated that the out-of-hospital shock index and respiratory rate have high predictability for ICU admission. Further studies should include the development of an out-of hospital sepsis score. PMID- 24229513 TI - A time to act. PMID- 24229514 TI - Public health consensus and point-of-care multiplex diagnostics for shipboard outbreak control. PMID- 24229515 TI - Emergent communication networks during disaster: an app for that. PMID- 24229516 TI - Nongovernmental resources to support disaster preparedness, response, and recovery. AB - OBJECTIVE: Although recent emergencies or disasters have underscored the vital role of nongovernmental (NGO) resources, they remain not well understood or leveraged. We intended to develop an assets framework that identifies relevant NGO resources for disaster preparedness and response that can be used to assess their availability at state and local levels. METHODS: We conducted a search of peer-reviewed publications to identify existing asset frameworks, and reviewed policy documents and gray literature to identify roles of NGOs in emergency preparedness, response, and recovery. A standardized data abstraction form was used to organize the results by NGO sector. RESULTS: We organized NGO assets into 5 categories: competencies, money, infrastructure or equipment, services, relationships, and data for each of the 11 sectors designated by the Centers for Disease Control and Prevention in the 2011 preparedness capabilities. CONCLUSIONS: Our findings showed that the capacity of each sector to capture data on each asset type needs strengthening so that data can be merged for just-in time analysis to indicate where additional relief is needed. PMID- 24229517 TI - Disaster documentation for the clinician. AB - Documentation of the patient encounter is a traditional component of health care practice, a requirement of various regulatory agencies and hospital oversight committees, and a necessity for reimbursement. A disaster may create unexpected challenges to documentation. If patient volume and acuity overwhelm health care providers, what is the acceptable appropriate documentation? If alterations in scope of practice and environmental or resource limitations occur, to what degree should this be documented? The conflicts arising from allocation of limited resources create unfamiliar situations in which patient competition becomes a component of the medical decision making; should that be documented, and, if so, how? In addition to these challenges, ever-present liability worries are compounded by controversies over the standards to which health care providers will be held. Little guidance is available on how or what to document. We conducted a search of the literature and found no appropriate references for disaster documentation, and no guidelines from professional organizations. We review here the challenges affecting documentation during disasters and provide a rationale for specific patient care documentation that avoids regulatory and legal pitfalls. PMID- 24229518 TI - Harnessing a community for sustainable disaster response and recovery: an operational model for integrating nongovernmental organizations. AB - OBJECTIVE: Nongovernmental organizations (NGOs) are important to a community during times of disaster and routine operations. However, their effectiveness is reduced without an operational framework that integrates response and recovery efforts. Without integration, coordination among NGOs is challenging and use of government resources is inefficient. We developed an operational model to specify NGO roles and responsibilities before, during, and after a disaster. METHODS: We conducted an analysis of peer-reviewed literature, relevant policy, and federal guidance to characterize the capabilities of NGOs, contextual factors that determine their involvement in disaster operations, and key services they provide during disaster response and recovery. We also identified research questions that should be prioritized to improve coordination and communication between NGOs and government. RESULTS: Our review showed that federal policy stresses the importance of partnerships between NGOs and government agencies and among other NGOs. Such partnerships can build deep local networks and broad systems that reach from local communities to the federal government. Understanding what capacities NGOs need and what factors influence their ability to perform during a disaster informs an operational model that could optimize NGO performance. CONCLUSIONS: Although the operational model needs to be applied and tested in community planning and disaster response, it holds promise as a unifying framework across new national preparedness and recovery policy, and provides structure to community planning, resource allocation, and metrics on which to evaluate NGO disaster involvement. PMID- 24229519 TI - Competency-based standardized training for humanitarian providers: making humanitarian assistance a professional discipline. AB - The number of people employed in international humanitarian care is growing at a yearly rate of 6%. The demand for better coordination, accountability, and training has led to a need for standardized humanitarian training programs for providers. Training should be based on comprehensive core competencies that providers must demonstrate in addition to their skill-specific competencies. This report explores the competencies specific to humanitarian training that are practice- and application-oriented, teachable, and measurable. Competency-based, standardized programs will be used to select humanitarian workers deployed in future crises and to guide the professionalization of this discipline. PMID- 24229520 TI - Building performance-based accountability with limited empirical evidence: performance measurement for public health preparedness. AB - Efforts to respond to performance-based accountability mandates for public health emergency preparedness have been hindered by a weak evidence base linking preparedness activities with response outcomes. We describe an approach to measure development that was successfully implemented in the Centers for Disease Control and Prevention Public Health Emergency Preparedness Cooperative Agreement. The approach leverages insights from process mapping and experts to guide measure selection, and provides mechanisms for reducing performance irrelevant variation in measurement data. Also, issues are identified that need to be addressed to advance the science of measurement in public health emergency preparedness. PMID- 24229521 TI - Assessment of the health impacts of the 2011 summer floods in Brisbane. AB - OBJECTIVE: To assess the effects of the 2011 floods in Brisbane, Australia, on residents' physical and mental health. METHODS: Residents who had been affected by the floods completed a community-based survey that examined the direct impact of flooding on households and their perceived physical and mental health. Outcome variables included overall and respiratory health and mental health outcomes related to psychological distress, sleep quality, and posttraumatic stress disorder (PTSD). Multivariable logistic regression was used to examine the association between flooding and perceived health outcome variables, adjusted for current health status and sociodemographic factors. RESULTS: Residents whose households were directly affected by flooding were more likely to report poor overall (Odds Ratio [OR] 5.3; 95% CI, 2.8-10.1) and respiratory (OR 2.3; 95% CI, 1.1-4.6) health, psychological distress (OR 1.9; 95% CI, 1.1-3.5), poor sleep quality (OR 2.3; 95% CI, 1.2-4.4), and probable PTSD (OR 2.3; 95% CI, 1.2-4.5). CONCLUSIONS: The 2011 Brisbane floods had significant impact on the physical and psychosocial health of residents. Improved support strategies may need to be integrated into existing disaster management programs to reduce flood-related health impacts, particularly those related to mental health. PMID- 24229522 TI - Resilience of Vietnamese refugees: resources to cope with natural disasters in their resettled country. AB - OBJECTIVE: Study findings suggest that refugees are more vulnerable than the general population to mental disorders from disasters. This pilot study explored the nature of Vietnamese refugees' resilience to a potential natural disaster as a first step toward improving their disaster mental health. METHODS: Interviews were conducted with 20 ethnic Vietnamese and Montagnard adult refugees using a semistructured interview guide. Factors in resilience at both individual and family levels were examined. RESULTS: Our results indicated that these refugees had positive personalities and strong family cohesion. However, although a majority of the participants had experienced natural disasters, they lacked knowledge and specific strategies to cope with these events. The individual participants and their families lacked sufficient information, financial resources, emergency supplies, or social support for a natural disaster. CONCLUSIONS: Enhancing refugees' current strengths in responding to disasters, delivering them tailored emergency training, strengthening relationships between refugee service providers and refugee communities, and advocating for refugees' socioeconomic capacity building should be considered. PMID- 24229523 TI - Nonclinical core competencies and effects of interprofessional teamwork in disaster and emergency response training and practice: a pilot study. AB - OBJECTIVE: To define and delineate the nontechnical core competencies required for disaster response, Disaster Medical Assistance Team (DMAT) members were interviewed regarding their perspectives and experiences in disaster management. Also explored was the relationship between nontechnical competencies and interprofessional collaboration. METHODS: In-depth interviews were conducted with 10 Canadian DMAT members to explore how they viewed nontechnical core competencies and how their experiences influenced their perceptions toward interprofessonalism in disaster response. Data were examined using thematic analysis. RESULTS: Nontechnical core competencies were categorized under austere skills, interpersonal skills, and cognitive skills. Research participants defined interprofessionalism and discussed the importance of specific nontechnical core competencies to interprofessional collaboration. CONCLUSIONS: The findings of this study established a connection between nontechnical core competencies and interprofessional collaboration in DMAT activities. It also provided preliminary insights into the importance of context in developing an evidence base for competency training in disaster response and management. (Disaster Med Public Health Preparedness. 2013;0:1-8). PMID- 24229524 TI - Using health insurance claim information for evacuee medical support and reconstruction after the Great East Japan Earthquake. AB - OBJECTIVE: Loss of patient information can hinder medical care for evacuees and the reconstruction of medical facilities damaged by major incidents. In Japan, health insurance coverage is universal, and information about diagnoses and health care services provided is shared by the medical facilities, Health Insurance Claims Review and Reimbursement Services or the National Health Insurance Organization (NHIO), and the insurers. After the Great East Japan Earthquake on March 11, 2011, we interviewed officers in charge of NHIO in the 3 prefectures that were damaged by the earthquake and elicited how they assisted with medical care for evacuees and reconstruction of the damaged medical facilities. METHODS: Comprehensive interviews were conducted with officers in charge of the NHIO in the 3 prefectures to obtain information about the use and provision of health insurance claims data 3 to 4 months after the event. We then analyzed the official data concerning use of the information from the claims in chronological order. RESULTS: The NHIO headquarters in the 3 prefectures were not physically affected by the disaster, and their information on the health insurance claims was intact. Patient information acquired before the disaster was obtained from the health insurance claims and applied to the medical care of the evacuees. The information also was used to reconstruct patient records lost in the disaster. CONCLUSION: The information that was obtained from health insurance claims was used to improve medical care after the large-scale disaster. PMID- 24229525 TI - Preparedness of anesthesiologists working in humanitarian disasters. AB - OBJECTIVE: Many skills needed to provide patients with safe, timely, and adequate anesthesia care during humanitarian crisis and disaster relief operations are not part of the daily routine before deployment. An exploratory study was conducted to identify preparedness, knowledge, and skills needed for deployment to complex emergencies. METHODS: Anesthesiologists who had been deployed during humanitarian crisis and disaster relief operations completed an online questionnaire assessing their preparedness, skills, and knowledge needed during deployment. Qualitative data were sorted by frequencies and similarities and clustered accordingly. RESULTS: Of 121 invitations sent out, 55 (46%) were completed and returned. Of these respondents, 24% did not feel sufficiently prepared for the deployment, and 69% did not undertake additional education for their missions. Insufficient preparedness involved equipment, drugs, regional anesthesia, and related management. CONCLUSIONS: As the lack of preparation and relevant training can create precarious situations, anesthesiologists and deploying agencies should improve preparedness for anesthesia personnel. (Disaster Med Public Health Preparedness. 2013;0;1-5). PMID- 24229526 TI - Testing the efficacy of homemade masks: would they protect in an influenza pandemic? AB - OBJECTIVE: This study examined homemade masks as an alternative to commercial face masks. METHODS: Several household materials were evaluated for the capacity to block bacterial and viral aerosols. Twenty-one healthy volunteers made their own face masks from cotton t-shirts; the masks were then tested for fit. The number of microorganisms isolated from coughs of healthy volunteers wearing their homemade mask, a surgical mask, or no mask was compared using several air sampling techniques. RESULTS: The median-fit factor of the homemade masks was one half that of the surgical masks. Both masks significantly reduced the number of microorganisms expelled by volunteers, although the surgical mask was 3 times more effective in blocking transmission than the homemade mask. CONCLUSION: Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection. PMID- 24229527 TI - Impacts of the emergency mass evacuation of the elderly from residential care facilities after the 2011 Christchurch earthquake. AB - OBJECTIVE: The 2011 earthquake that devastated Christchurch, New Zealand, led to the closure and evacuation of 7 residential care facilities and the partial evacuation of 2 more. Altogether, 516 elderly persons were evacuated. The emergent nature of the disaster was unexpected and largely unplanned for. This study explored the evacuees' experiences and identified lessons learned for future disaster planning. METHODS: This qualitative study used a general inductive method. Semistructured interviews with evacuees were held in 4 centers throughout New Zealand. Their informal caregivers were also identified and interviewed. Answers were coded and grouped for key themes to provide lessons learned for future disaster planning. RESULTS: We conducted 50 interviews with older people and 34 with informal caregivers. Key themes that emerged were resilience and factors that promoted resilience, including personal attitudes, life experiences, enhanced family support, and social supports. Areas of concern were (1) the mental health of evacuees: 36% reported some symptoms of anxiety, while 32.4% of caregivers reported some cognitive decline; and (2) communication difficulties during the evacuations. CONCLUSIONS: Older people were remarkably resilient to the difficult events, and resilience was promoted by family and community support. Anxiety was reported by older people, while informal caregivers reported cognitive issues. Communication difficulties were a major concern. PMID- 24229528 TI - Using participatory action research to identify strategies to improve pandemic vaccination. AB - OBJECTIVE: Developing and implementing effective strategies to increase influenza vaccination rates among health care personnel is an ongoing challenge, especially during a pandemic. We used participatory action research (PAR) methodology to identify targeted vaccination interventions that could potentially improve vaccine uptake in a medical center. METHODS: Front-line medical center personnel were recruited to participate in 2 PAR teams (clinical and nonclinical staff). Data from a recent medical center survey on barriers and facilitators to influenza (seasonal, pandemic, and combination) vaccine uptake were reviewed, and strategies to increase vaccination rates among medical center personnel were identified. RESULTS: Feasible, creative, and low-cost interventions were identified, including organizational strategies that differed from investigator identified interventions. The recommended strategies also differed by team. The nonclinical team suggested programs focused on dispelling vaccination-related myths, and the clinical team suggested campaigns emphasizing the importance of vaccination to protect patients. CONCLUSIONS: PAR methodology was useful to identify innovative and targeted recommendations for increasing vaccine uptake. By involving representative front-line workers, PAR may help medical centers improve influenza vaccination rates across all work groups. PMID- 24229529 TI - Comparing acquisition of radiation health knowledge and preventive behavior of working adults during and after the Fukushima disaster. PMID- 24229530 TI - Emergency response to mass casualty incidents in Lebanon. AB - The emergency response to mass casualty incidents in Lebanon lacks uniformity. Three recent large-scale incidents have challenged the existing emergency response process and have raised the need to improve and develop incident management for better resilience in times of crisis. We describe some simple emergency management principles that are currently applied in the United States. These principles can be easily adopted by Lebanon and other developing countries to standardize and improve their emergency response systems using existing infrastructure. PMID- 24229531 TI - Maternal fatty acids and offspring development: extending beyond the cardiovascular and endocrine systems. PMID- 24229532 TI - Seoul virus in rats (Rattus norvegicus), Hyesan, North Korea, 2009-2011. PMID- 24229533 TI - Social support and health among elderly Kuwaitis. AB - The aim of this study was to examine differences in several aspects of health between Kuwaiti men and women aged 60 years and over across three age categories (60-69, 70-79, 80+ years). The relationships between several social support variables, somatic symptoms and systolic and diastolic blood pressures were examined. A total of 1427 adult men (472) and women (955) aged 60 years and over representing all six governorates were selected. Data were collected during 2008 2009 by interview and completion of a questionnaire by participants in their own homes, after obtaining their informed consent. The Social Support Scale (SSS), Frequency of Contact Scale (FOC), Strength of Relations (SOR), Somatic Symptoms Inventory (SSI) and self-rated scales of general health were included. Systolic and diastolic blood pressures were measured. The data show that self-rated health and health in the last year differ significantly across age groups. Glycaemia differed significantly across the three age groups for the total sample. Systolic and diastolic blood pressure were higher in older respondents than younger ones, but no significant differences were observed between men and women. No significant differences in somatic symptoms were observed across the three age groups. Strength of relationship, frequency of contact, social support and children living with an elderly adult were all associated with fewer somatic symptoms, and all, except social support, were associated with lower systolic and diastolic blood pressure. Having children, the perception of social support, frequency of contact with, and strength of, relationships with kin are important modulators of somatic symptoms and blood pressure among elderly Kuwaitis. PMID- 24229534 TI - Segmental distributions and consonant-vowel association patterns in Japanese infant- and adult-directed speech. AB - Japanese infant-directed speech (IDS) and adult-directed speech (ADS) were compared on their segmental distributions and consonant-vowel association patterns. Consistent with findings in other languages, a higher ratio of segments that are generally produced early was found in IDS compared to ADS: more labial consonants and low-central vowels, but fewer fricatives. Consonant-vowel associations also favored the early produced labial-central, coronal-front, coronal-central, and dorsal-back patterns. On the other hand, clear language specific patterns included a higher frequency of dorsals, affricates, geminates, and moraic nasals in IDS. These segments are frequent in adult Japanese, but not in the early productions or the IDS of other studied languages. In combination with previous results, the current study suggests that both fine-tuning (an increased use of early produced segments) and highlighting (an increased use of language-specifically relevant segments) might modify IDS on the segmental level. PMID- 24229535 TI - Methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphism is associated with antipsychotic-induced weight gain in first-episode schizophrenia. AB - Genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism may be important predictors of antipsychotic drug induced weight gain (AIWG). We tested whether two functional MTHFR polymorphisms are related to AIWG. Weight gain was studied in two cohorts of first-episode, initially drug-naive schizophrenia patients; Chinese Han (n = 182) and Spanish Caucasians (n = 72) receiving antipsychotics for 10 wk and 3 months respectively. Blood DNA was genotyped for 677C/T and 1298A/C MTHFR polymorphisms. Patients with the 677 CC genotype had a significantly greater increase in BMI compared to T allele carriers in both Chinese (p = 0.012) and Spanish (p = 0.017) samples. The 677C/T MTHFR polymorphism showed an additive effect, but no significant interaction, with the -759C/T HTR2C polymorphism previously associated with AIWG. These results suggest that the 677C/T MTHFR polymorphism might, along with the 759C/T HTR2C polymorphism and other genetic factors, provide a useful marker for the important and limiting side effect of AIWG. PMID- 24229536 TI - Stress and the healthy adolescent brain: evidence for the neural embedding of life events. AB - Little is known about the long-term neural consequences of adverse life events for healthy adolescents, and this is particularly the case for events that occur after a putative stress-sensitive period in early childhood. In this functional magnetic resonance imaging study of healthy adolescents, we found that prior exposure to severe adverse life events was associated with current anxiety and with increased amygdala reactivity to standardized emotional stimuli (viewing of fearful faces relative to calm ones). Conjunction analyses identified multiple regions, including the amygdala, insula, and prefrontal cortex, in which reactivity to emotional faces covaried with life events as well as with current anxiety. Our morphometric analyses suggest systemic alterations in structural brain development with an association between anxiety symptoms and global gray matter volume. No life events were reported for the period before 4 years of age, suggesting that these results were not driven by exposure to stress during an early sensitive period in development. Overall, these data suggest systemic effects of traumatic events on the dynamically developing brain that are present even in a nonclinical sample of adolescents. PMID- 24229537 TI - Origins of children's externalizing behavior problems in low-income families: toddlers' willing stance toward their mothers as the missing link. AB - Although children's active role in socialization has been long acknowledged, relevant research has typically focused on children's difficult temperament or negative behaviors that elicit coercive and adversarial processes, largely overlooking their capacity to act as positive, willing, even enthusiastic, active socialization agents. We studied the willing, receptive stance toward their mothers in a low-income sample of 186 children who were 24 to 44 months old. Confirmatory factor analysis supported a latent construct of willing stance, manifested as children's responsiveness to mothers in naturalistic interactions, responsive imitation in teaching contexts, and committed compliance with maternal prohibitions, all observed in the laboratory. Structural equation modeling analyses confirmed that ecological adversity undermined maternal responsiveness, and responsiveness, in turn, was linked to children's willing stance. A compromised willing stance predicted externalizing behavior problems, assessed 10 months later, and fully mediated the links between maternal responsiveness and those outcomes. Ecological adversity had a direct, unmediated effect on internalizing behavior problems. Considering children's active role as willing, receptive agents capable of embracing parental influence can lead to a more complete understanding of detrimental mechanisms that link ecological adversity with antisocial developmental pathways. It can also inform research on the normative socialization process, consistent with the objectives of developmental psychopathology. PMID- 24229538 TI - Observed parenting behaviors interact with a polymorphism of the brain-derived neurotrophic factor gene to predict the emergence of oppositional defiant and callous-unemotional behaviors at age 3 years. AB - Using the Durham Child Health and Development Study, this study (N = 171) tested whether observed parenting behaviors in infancy (6 and 12 months) and toddlerhood/preschool (24 and 36 months) interacted with a child polymorphism of the brain-derived neurotrophic factor gene to predict oppositional defiant disorder (ODD) and callous-unemotional (CU) behaviors at age 3 years. Child genotype interacted with observed harsh and intrusive (but not sensitive) parenting to predict ODD and CU behaviors. Harsh-intrusive parenting was more strongly associated with ODD and CU for children with a methionine allele of the brain-derived neurotrophic factor gene. CU behaviors were uniquely predicted by harsh-intrusive parenting in infancy, whereas ODD behaviors were predicted by harsh-intrusive parenting in both infancy and toddlerhood/preschool. The results are discussed from the perspective of the contributions of caregiving behaviors as contributing to distinct aspects of early onset disruptive behavior. PMID- 24229539 TI - Preventive interventions and sustained attachment security in maltreated children. AB - Thirteen-month-old maltreated infants (n = 137) and their mothers were randomly assigned to one of three conditions: child-parent psychotherapy (CPP), psychoeducational parenting intervention (PPI), or community standard (CS). A fourth group of nonmaltreated infants (n = 52) and their mothers served as a nonmaltreated comparison (NC) group. A prior investigation found that the CPP and the PPI groups demonstrated substantial increases in secure attachment at postintervention, whereas this change was not found in the CS and the NC groups. The current investigation involved the analysis of data obtained at a follow-up assessment that occurred 12 months after the completion of treatment. At follow up, children in the CPP group had higher rates of secure and lower rates of disorganized attachment than did children in the PPI or the CS group. Rates of disorganized attachment did not differ between the CPP and the NC groups. Intention to treat analyses also showed higher rates of secure attachment at follow-up in the CPP group relative to the PPI and the CS groups. However, groups did not differ on disorganized attachment. Both primary and intention to treat analyses demonstrated that maternal-reported child behavior problems did not differ among the four groups at the follow-up assessment. This is the first investigation to demonstrate sustained attachment security in maltreated children 12 months after the completion of an attachment theory informed intervention. The findings also suggest that, although effective in the short term, parenting interventions alone may not be effective in maintaining secure attachment in children over time. PMID- 24229540 TI - Patterns of brain activation in foster children and nonmaltreated children during an inhibitory control task. AB - Children in foster care have often encountered a range of adverse experiences, including neglectful and/or abusive care and multiple caregiver transitions. Prior research findings suggest that such experiences negatively affect inhibitory control and the underlying neural circuitry. In the current study, event-related functional magnetic resonance imaging was employed during a go/no go task that assesses inhibitory control to compare the behavioral performance and brain activation of foster children and nonmaltreated children. The sample included two groups of 9- to 12-year-old children: 11 maltreated foster children and 11 nonmaltreated children living with their biological parents. There were no significant group differences on behavioral performance on the task. In contrast, patterns of brain activation differed by group. The nonmaltreated children demonstrated stronger activation than did the foster children across several regions, including the right anterior cingulate cortex, the middle frontal gyrus, and the right lingual gyrus, during correct no go trials, whereas the foster children displayed stronger activation than the nonmaltreated children in the left inferior parietal lobule and the right superior occipital cortex, including the lingual gyrus and cuneus, during incorrect no go trials. These results provide preliminary evidence that the early adversity experienced by foster children impacts the neural substrates of inhibitory control. PMID- 24229541 TI - Stress reactivity in war-exposed young children with and without posttraumatic stress disorder: relations to maternal stress hormones, parenting, and child emotionality and regulation. AB - The current study examined biomarkers of stress in war-exposed young children and addressed maternal and child factors that may correlate with children's stress response. Participants were 232 Israeli children aged 1.5-5 years, including 148 children exposed to continuous war. Similarly, 56 were diagnosed with posttraumatic stress disorder (PTSD) and 92 were defined as exposed-no-PTSD. Child cortisol (CT) and salivary alpha amylase (sAA), biomarkers of the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary arms of the stress response, were measured at baseline, following challenge, and at recovery. Maternal CT and sAA, PTSD symptoms, and reciprocal parenting, and child negative emotionality and regulatory strategies were assessed. Differences between war exposed children and controls emerged, but these were related to child PTSD status. Children with PTSD exhibited consistently low CT and sAA, exposed-no-PTSD displayed consistently high CT and sAA, and controls showed increase in CT following challenge and decrease at recovery and low sAA. Exposed children showed higher negative emotionality; however, whereas exposed-no-PTSD children employed comfort-seeking strategies, children with PTSD used withdrawal. Predictors of child CT included maternal CT, PTSD symptoms, low reciprocity, and negative emotionality. Findings suggest that high physiological arousal combined with approach strategies may be associated with greater resilience in the context of early trauma. PMID- 24229542 TI - Maternal responsiveness and sensitivity reconsidered: some is more. AB - Is it always or necessarily the case that common and important parenting practices are better, insofar as they occur more often, or worse, because they occur less often? Perhaps, less is more, or some is more. To address this question, we studied mothers' microcoded contingent responsiveness to their infants (M = 5.4 months, SD = 0.2) in relation to independent global judgments of the same mothers' parenting sensitivity. In a community sample of 335 European American dyads, videorecorded infant and maternal behaviors were timed microanalytically throughout an extended home observation; separately and independently, global maternal sensitivity was rated macroanalytically. Sequential analysis and spline regression showed that, as maternal contingent responsiveness increased, judged maternal sensitivity increased to significance on the contingency continuum, after which mothers who were even more contingent were judged less sensitive. Just significant levels of maternal responsiveness are deemed optimally sensitive. Implications of these findings for typical and atypical parenting, child development, and intervention science are discussed. PMID- 24229544 TI - Differential susceptibility in longitudinal models of gene-environment interaction for adolescent depression. AB - Although family support reliably predicts the development of adolescent depression and suicidal behaviors, relatively little is known about the interplay of family support with potential genetic factors. We tested the association of the 44 base pair polymorphism in the serotonin transporter linked promoter region gene (5-HTTLPR), family support (i.e., cohesion, communication, and warmth), and their interaction with self-reported depression symptoms and risk for suicide in 1,030 Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health. High-quality family support predicted fewer symptoms of depression and reduced risk for suicidality. There was also a significant interaction between 5-HTTLPR and family support for boys and a marginally significant interaction for girls. Among boys with poor family support, youth with at least one short allele had more symptoms of depression and a higher risk for suicide attempts relative to boys homozygous for the long allele. However, in the presence of high family support, boys with the short allele had the fewest depression symptoms (but not suicide attempts). Results suggest that the short allele may increase reactivity to both negative and positive family influences in the development of depression. We discuss the potential role of interactive exchanges between family support and offspring genotype in the development of adolescent depression and suicidal behaviors. PMID- 24229543 TI - Developmental timing and continuity of exposure to interparental violence and externalizing behavior as prospective predictors of dating violence. AB - This study investigated the prospective pathways of children's exposure to interparental violence (EIPV) in early and middle childhood and externalizing behavior in middle childhood and adolescence as developmental predictors of dating violence perpetration and victimization at ages 23 and 26 years. Participants (N = 168) were drawn from a longitudinal study of low-income families. Path analyses examined whether timing or continuity of EIPV predicted dating violence and whether timing or continuity of externalizing behavior mediated these pathways. Results indicated that EIPV in early childhood directly predicted perpetration and victimization at age 23. There were significant indirect effects from EIPV to dating violence through externalizing behavior in adolescence and life stress at age 23. Independent of EIPV, externalizing behavior in middle childhood also predicted dating violence through externalizing behavior in adolescence and life stress at age 23, but this pathway stemmed from maltreatment. These results highlight that the timing of EIPV and both the timing and the continuity of externalizing behavior are critical risks for the intergenerational transmission of dating violence. The findings support a developmental perspective that negative early experiences and children's externalizing behavior are powerful influences for dating violence in early adulthood. PMID- 24229545 TI - Symptom differentiation of anxiety and depression across youth development and clinic-referred/nonreferred samples: An examination of competing factor structures of the Child Behavior Checklist DSM-oriented scales. AB - This study examined the psychometric properties of the DSM-oriented scales of the Child Behavior Checklist (Achenbach, Dumenci, & Rescorla, 2003) using confirmatory factor analysis to compare the six-factor structure of the DSM oriented scales to competing models consistent with developmental theories of symptom differentiation. We tested these models on both clinic-referred (N = 757) and school-based, nonreferred (N = 713) samples of youths in order to assess the generalizability of the factorial structures. Although previous research has supported the fit of the six-factor DSM-oriented structure in a normative sample of youths ages 7 to 18 (Achenbach & Rescorla, 2001), tripartite model research indicates that anxiety and depressive symptomology are less differentiated among children compared to adolescents (Jacques & Mash, 2004). We thus examined the relative fit of a six- and a five-factor model (collapsing anxiety and depression) with younger (ages 7-10) and older (ages 11-18) youth subsamples. The results revealed that the six-factor model fit the best in all samples except among younger nonclinical children. The results extended the generalizability of the rationally derived six-factor structure of the DSM-oriented scales to clinic referred youths and provided further support to the notion that younger children in nonclinical samples exhibit less differentiated symptoms of anxiety and depression. PMID- 24229546 TI - Early menarche predicts increased depressive symptoms and cortisol levels in Quebec girls ages 11 to 13. AB - Earlier age of menarche is believed to confer greater vulnerability to depressive symptoms via increased reactivity to stressors associated with adolescence. In this longitudinal study, we measured depressive symptoms and salivary cortisol levels in 198 boys and 142 girls between the ages of 11 and 13 tested four times during Grade 7 as they transitioned from elementary school to secondary school as per Quebec's education system. Results showed that girls who had already reached menarche before starting secondary school had significantly higher depressive symptoms and salivary cortisol levels across the school year in comparison to girls who had not reached menarche, who in turn presented higher depressive scores than boys. When we divided menarcheal girls as a function of menarcheal timing in subanalyses, we found that girls with early menarche presented consistently elevated depressive symptoms across the school year while girls with on-time menarche presented transient depressive symptoms but no differences in salivary cortisol levels. Collectively, these results show that early menarche is associated with high depressive symptoms and cortisol levels in adolescent girls. This developmental milestone may render girls more vulnerable to environmental stressors and therefore represents a critical period to intervene to promote mental health. PMID- 24229547 TI - Interaction matters: quantifying conduct problem * depressive symptoms interaction and its association with adolescent alcohol, cigarette, and marijuana use in a national sample. AB - Substance use is a major contributor to morbidity and mortality among American adolescents. Conduct problems and depressive symptoms have each been found to be associated with adolescent substance use. Although they are highly comorbid, the role of the interaction of conduct problems and depressive symptoms in substance use is not clear. In national samples of 8th-, 10th-, and 12th-grade students from the Monitoring the Future study, latent moderated structural equation modeling was used to estimate the association of conduct problems, depressive symptoms, and their interaction to the use of alcohol (including binge drinking), cigarettes, and marijuana. Moderation by age and sex was tested. The interaction of conduct problems with depressive symptoms was a strong predictor of substance use, particularly among younger adolescents. With few exceptions, adolescents with high levels of both conduct problems and depressive symptoms used substances most frequently. Conduct problems were a strong positive predictor of substance use, and depressive symptoms were a weak positive predictor. Whereas conduct problems are often thought to be a primary predictor of substance use, this study revealed that depressive symptoms potentiate the relation of conduct problems to substance use. Therefore, substance use prevention efforts should target both depressive symptoms and conduct problems. PMID- 24229548 TI - Exposure to maternal pre- and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring. AB - This study evaluated whether exposure to maternal pre- or postnatal depression or anxiety symptoms predicted psychopathology in adolescent offspring. Growth mixture modeling was used to identify trajectories of pre- and postnatal depression and anxiety symptoms in 577 women of low socioeconomic status selected from a prenatal clinic. Logistic regression models indicated that maternal pre- and postnatal depression trajectory exposure was not associated with offspring major depression, anxiety, or conduct disorder, but exposure to the high depression trajectory was associated with lower anxiety symptoms in males. Exposure to medium and high pre- and postnatal anxiety was associated with the risk of conduct disorder among offspring. Male offspring exposed to medium and high pre- and postnatal anxiety had higher odds of conduct disorder than did males with low exposure levels. Females exposed to medium or high pre- and postnatal anxiety were less likely to meet conduct disorder criteria than were females with lower exposure. To the best of our knowledge, this is the first study to examine the effect of pre- and postnatal anxiety trajectories on the risk of conduct disorder in offspring. These results suggest new directions for investigating the etiology of conduct disorder with a novel target for intervention. PMID- 24229550 TI - The development of thought problems: a longitudinal family risk study of offspring of bipolar, unipolar, and well parents. AB - There is growing evidence that many offspring of parents with bipolar disorder (BD) will develop moderate to severe forms of psychopathology during childhood and adolescence, including thought problems. The purpose of this study was to evaluate the developmental progression of thought problems within the context of a family risk study. Repeated assessments of thought problems, spanning approximately 15 years, were conducted in offspring (N = 192 from 98 families) of parents diagnosed with BD (O-BD), unipolar depression (O-UNI), or no significant psychiatric or medical problems (O-WELL). Survival analysis showed that the O-BD group had the greatest estimated probability of developing thought problems over time, followed by O-UNI, and then O-WELL and O-BD exhibiting higher levels of persistence than O-WELL. Parent-reported thought problems in childhood and adolescence predicted a range of problems in young adulthood. Disturbances in reality testing and other atypical behaviors are likely to disrupt progression through important developmental periods and to associate with poor outcomes. These findings are likely relevant to preventing the occurrence or progression of problems in offspring of bipolar parents. The study of thought problems across development represents an important area of continued research in children at risk for development of affective disorders. PMID- 24229549 TI - The efficacy of interpersonal psychotherapy for depression among economically disadvantaged mothers. AB - A randomized clinical trial was conducted to evaluate the efficacy of interpersonal psychotherapy (IPT) for ethnically and racially diverse, economically disadvantaged women with major depressive disorder. Non-treatment seeking urban women (N = 128; M age = 25.40, SD = 4.98) with infants were recruited from the community. Participants were at or below the poverty level: 59.4% were Black and 21.1% were Hispanic. Women were screened for depressive symptoms using the Center for Epidemiologic Studies Depression Scale; the Diagnostic Interview Schedule was used to confirm major depressive disorder diagnosis. Participants were randomized to individual IPT or enhanced community standard. Depressive symptoms were assessed before, after, and 8 months posttreatment with the Beck Depression Inventory-II and the Revised Hamilton Rating Scale for Depression. The Social Support Behaviors Scale, the Social Adjustment Scale-Self-Report, and the Perceived Stress Scale were administered to examine mediators of outcome at follow-up. Treatment effects were evaluated with a growth mixture model for randomized trials using complier-average causal effect estimation. Depressive symptoms trajectories from baseline through postintervention to follow-up showed significant decreases among the IPT group compared to the enhanced community standard group. Changes on the Perceived Stress Scale and the Social Support Behaviors Scale mediated sustained treatment outcome. PMID- 24229551 TI - Psychosocial (im)maturity from adolescence to early adulthood: distinguishing between adolescence-limited and persisting antisocial behavior. AB - In the psychological tradition, desistance from antisocial behavior is viewed as the product of psychosocial maturation, including increases in the ability to control impulses, consider the implications of one's actions on others, delay gratification in the service of longer term goals, and resist the influences of peers. The present study investigates how individual variability in the development of psychosocial maturity is associated with desistance from antisocial behavior in a sample of 1,088 serious juvenile offenders followed from adolescence to early adulthood (ages 14-25). We find that psychosocial maturity continues to develop to the midtwenties and that different developmental patterns of maturation are found among those who desist and those who persist in antisocial behavior. Compared to individuals who desisted from antisocial behavior, youths who persisted exhibited diminished development of psychosocial maturity. Moreover, earlier desistance compared to later desistance is linked to greater psychosocial maturity, suggesting that there is an association between desistance from antisocial behavior and normative increases in psychosocial maturity. PMID- 24229552 TI - Dopamine receptor D4 gene moderates the effect of positive and negative peer experiences on later delinquency: the Tracking Adolescents' Individual Lives Survey study. AB - The quality of adolescents' relationships with peers can have a lasting impact on later psychosocial adjustment, mental health, and behavior. However, the effect of peer relations on later problem behavior is not uniformly strong, and genetic factors might influence this association. This study used four-wave longitudinal (11-19 years) data (n = 1,151) from the Tracking Adolescents' Individual Lives Survey, a Dutch cohort study into adolescent development to test whether the dopamine receptor D4 polymorphism moderates the impact of negative (i.e., victimization) and positive peer experiences (i.e., social well-being) on later delinquency. Contrary to our expectations, results showed that carriers of the dopamine receptor D4 gene 4-repeat homozygous variant instead of those carrying the 7-repeat allele were more susceptible to the effects of both peer victimization and social well-being on delinquency later in adolescence. Findings of our study are discussed in light of other studies into genetic moderation of peer effects on adolescent development and the possibility that developmental specifics in adolescence, such as maturation processes in brain structure and functioning, may affect the interplay of environmental and genetic factors in this period in life. PMID- 24229553 TI - Blunted feedback processing during risky decision making in adolescents with a parental history of substance use disorders. AB - Risky decision making, a hallmark phenotype of substance use disorders (SUD), is thought to be associated with deficient feedback processing. Whether these aberrations are present prior to SUD onset or reflect merely a consequence of chronic substance use on the brain remains unclear. The present study investigated whether blunted feedback processing during risky decision making reflects a biological predisposition to SUD. We assessed event-related potentials elicited by positive and negative feedback during performance of a modified version of the Balloon Analogue Risk Task (BART) among high-risk adolescents with a parental history of SUD (HR; n = 61) and normal-risk controls (NR; n = 91). HR males made significantly more risky and faster decisions during the BART than did NR controls. Moreover, HR adolescents showed significantly reduced P300 amplitudes in response to both positive and negative feedback as compared to NR controls. These differences were not secondary to prolonged substance use exposure. Results are discussed in terms of feedback-specific processes. Reduced P300 amplitudes in the BART may reflect poor processing of feedback at the level of overall salience, which may keep people from effectively predicting the probability of future gains and losses. Though conclusions are tentative, blunted feedback processing during risky decision making may represent a promising endophenotypic vulnerability marker for SUD. PMID- 24229554 TI - Maturing out of alcohol involvement: transitions in latent drinking statuses from late adolescence to adulthood. AB - Research has shown a developmental process of "maturing out" of alcohol involvement beginning in young adulthood, but the precise nature of changes characterizing maturing out is unclear. We used latent transition analysis to investigate these changes in a high-risk sample from a longitudinal study of familial alcoholism (N = 844; 51% children of alcoholics; 53% male, 71% non Hispanic Caucasian, 27% Hispanic). Analyses classified participants into latent drinking statuses during late adolescence (ages 17-22), young adulthood (ages 23 28), and adulthood (ages 29-40), and characterized transitions among these statuses over time. The resulting four statuses were abstainers, low-risk drinkers who typically drank less than weekly and rarely binged or showed drinking problems, moderate-risk drinkers who typically binged less than weekly and showed moderate risk for drinking problems, and high-risk drinkers who typically binged at least weekly and showed high risk for drinking problems. Maturing out between late adolescence and young adulthood was most common among initial high-risk drinkers, but they typically declined to moderate-risk drinking rather than to nonrisky drinking statuses. This suggests that the developmental phenomenon of maturing out pertains primarily to relatively high-risk initial drinkers and that many high-risk drinkers who mature out merely reduce rather than eliminate their risky drinking. PMID- 24229555 TI - Trajectories of multiple adolescent health risk behaviors in a low-income African American population. AB - This study examined interdependent trajectories of sexual risk, substance use, and conduct problems among 12- to 18-year-old African American youths who were followed annually as part of the Mobile Youth Study. We used growth mixture modeling to model the development of these three outcomes in the 1,406 participants who met the inclusion criteria. Results indicate that there were four distinct classes: normative, low risk (74.3% of sample); increasing high risk takers (11.9%); adolescent-limited conduct problems and drug risk with high risky sex (8.0%); and early experimenters (5.8%) The higher risk classes had higher rates of pregnancy and sexually transmitted infections diagnoses than the normative sample at each of the ages we examined. Differing somewhat from our hypothesis, all of the nonnormative classes exhibited high sexual risk behavior. Although prevention efforts should be focused on addressing all three risk behaviors, the high rate of risky sexual behavior in the 25% of the sample that fall into the three nonnormative classes underscores an urgent need for improved sex education, including teen pregnancy and HIV/sexually transmitted infections prevention, in this community. PMID- 24229558 TI - A comparative study of the effect of triage training by role-playing and educational video on the knowledge and performance of emergency medical service staffs in Iran. AB - INTRODUCTION: Educating emergency medical staffs in triage skills is an important aspect of disaster preparedness. The aim of the study was to compare the effect of role-playing and educational video presentation on the learning and performance of the emergency medical service staffs in Khozestan, Iran METHODS: A total of 144 emergency technicians were randomly classified into two groups. A researcher trained the first group using an educational video method and the second group with a role-playing method. Data were collected before, immediately, and 15 days after training using a questionnaire covering the three domains of demographic information, triage knowledge, and triage performance. The data were analyzed using defined knowledge and performance parameters. RESULTS: There was no significant difference between the two training methods on performance and immediate knowledge (P = .2), lasting knowledge (P=.05) and immediate performance (P = .35), but there was a statistical advantage for the role-playing method on lasting performance (P = .02). CONCLUSION: The two educational methods equally increase knowledge and performance, but the role-playing method may have a more desirable and lasting effect on performance. PMID- 24229556 TI - Premorbid functional development and conversion to psychosis in clinical high risk youths. AB - Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study-I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention. PMID- 24229557 TI - Reciprocal social behavior in youths with psychotic illness and those at clinical high risk. AB - Youths at clinical high risk (CHR) for psychosis typically exhibit significant social dysfunction. However, the specific social behaviors associated with psychosis risk have not been well characterized. We administer the Social Responsiveness Scale (SRS), a measure of autistic traits that examines reciprocal social behavior, to the parents of 117 adolescents (61 CHR individuals, 20 age matched adolescents with a psychotic disorder [AOP], and 36 healthy controls) participating in a longitudinal study of psychosis risk. AOP and CHR individuals have significantly elevated SRS scores relative to healthy controls, indicating more severe social deficits. Mean scores for AOP and CHR youths are typical of scores obtained in individuals with high functioning autism (Constantino & Gruber, 2005). SRS scores are significantly associated with concurrent real-world social functioning in both clinical groups. Finally, baseline SRS scores significantly predict social functioning at follow-up (an average of 7.2 months later) in CHR individuals, over and above baseline social functioning measures (p < .009). These findings provide novel information regarding impairments in domains critical for adolescent social development, because CHR individuals and those with overt psychosis show marked deficits in reciprocal social behavior. Further, the SRS predicts subsequent real-world social functioning in CHR youth, suggesting that this measure may be useful for identifying targets of treatment in psychosocial interventions. PMID- 24229559 TI - Is the use of accurate psychiatric labels associated with intentions and beliefs about responses to mental illness in a friend? Findings from two national surveys of Australian youth. AB - Aims. An inherent prerequisite to mental health first-aid (MHFA) is the ability to identify that there is a mental health problem, but little is known about the association between psychiatric labelling and MHFA. This study examined this association using data from two national surveys of Australian young people. Methods. This study involved a national telephonic survey of 3746 Australian youth aged 12-25 years in 2006, and a similar survey in 2011 with 3021 youth aged 15-25 years. In both surveys, respondents were presented with a vignette portraying depression, psychosis or social phobia in a young person. The 2011 survey also included depression with suicidal thoughts and post-traumatic stress disorder. Respondents were asked what they thought was wrong with the person, and reported on their first-aid intentions and beliefs, which were scored for quality of the responses. Results. Accurate labelling of the mental disorder was associated with more helpful first-aid intentions and beliefs across vignettes, except for the intention to listen non-judgementally in the psychosis vignette. Conclusions. Findings suggest that community education programmes that improve accurate psychiatric label use may have the potential to improve the first-aid responses young people provide to their peers, although caution is required in the case of psychosis. PMID- 24229560 TI - Interactions between plasma concentrations of folate and markers of vitamin B(12) status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study. AB - A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-E4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0.009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18.5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0.22, 95 % CI 0.05, 0.92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest. PMID- 24229561 TI - Changing age patterns of morbidity vis-a-vis mortality in India. AB - The combined effects of decreased fertility and mortality coupled with increasing survivorship across most ages have been upsetting the levels and age patterns of morbidity and mortality in India. This study examined data from the National Sample Survey (NSS) and Sample Registration System (SRS) of India. The results reveal marked structural changes in the age patterns of morbidity and mortality. The analysis also tested whether morbidity contours are being compressed or expanded, connecting it with the ongoing processes of demographic and epidemiological transition. The Sullivan (1971) method was used to estimate the health ratio over three time periods to ascertain the expansion of morbidity. The results reveal an exceptional rise in the prevalence rate of chronic non communicable diseases in ages 60 and above. The proportion of unhealthy years of the total life expectancy has increased more than before for all older age groups. Overall, the results confirm that an expansion of morbidity is in progress, with a heavier and cumulated concentration of morbidity in older ages. The expansion of morbidity hypothesis is validated for major categories of population: rural, urban, male and female. Older females bear a much heavier burden of chronic non-communicable diseases and are vulnerable to a higher proportion of unhealthy years. The age-structural shifts in morbidity and mortality signal the steady progress of epidemiological transition in India. PMID- 24229562 TI - Learning a generative syntax from transparent syntactic atoms in the linguistic input. AB - We examined parents' two-word utterances expressing core syntactic relations in order to test the hypothesis that they may enable children to derive the atoms of hierarchical syntax, namely, the asymmetrical Merge/Dependency relation between pairs of words, and, in addition, to identify variables serving generative syntactic rules. Using a large English-language parental corpus, we located all two-word utterances containing a verb and its subject, object, or indirect object. Analysis showed that parental two-word sentences contain transparent information on the binary dependency/merge relation responsible for syntactic connectivity. The syntactic atoms modelled in the two-word input contain natural variables for dependents, making generalization to other contexts an immediate possibility. In a second study, a large sample of children were found to use the same verbs in the great majority of their early sentences expressing the same core grammatical relations. The results support a learning model according to which children learn the basics of syntax from parental two-word sentences. PMID- 24229563 TI - Three outbreak-causing Neisseria meningitidis serogroup C clones, Brazil(1.). AB - During 2003-2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates. PMID- 24229565 TI - Entacapone augmentation of antipsychotic treatment in schizophrenic patients with negative symptoms; a double-blind placebo-controlled study. AB - Negative symptoms in schizophrenia are associated with decreased dopaminergic activity in the prefrontal cortex (PFC). It is hypothesized that increasing dopamine levels would alleviate negative symptoms. Termination of dopamine activity in the PFC is mainly via catechol-O-methyl tranferase (COMT) activity. Hence, inhibition of COMT activity with entacapone should reverse PFC dopaminergic transmission. To assess the efficacy of entacapone addition to antipsychotic treatment in patients with residual schizophrenia, we conducted a double-blind, randomised, placebo-controlled study for 12 wk of treatment with entacapone or placebo. Clinical measures (PANSS, CGI and QLS) were obtained at baseline and at weeks 4, 8 and 12 and cognitive functions were assessed by the RBANSS. Significant improvement over time in PANSS and QLS scores was observed in both groups. However, entacapone did not demonstrate a beneficial effect compared to placebo. Therefore, this study does not support a therapeutic role for entacapone in residual schizophrenia. PMID- 24229566 TI - State, territorial, and local health departments' reporting of partnership strength before and after the H1N1 response. AB - INTRODUCTION: Research has shown that partnerships between public health agencies, service providers, and other key stakeholders can expand resources and facilitate focus on community health issues more effectively than can any agency or organization acting alone. There is, however, little empirical evidence drawn from actual public health emergency responses to support this claim. The US response to novel influenza A (H1N1) virus provided the Centers for Disease Control and Prevention (CDC) the opportunity to explore whether, and the extent to which, state, local and territorial health departments strengthened partnerships with key partner agencies and sectors. METHODS: Participants included the CDC Public Health Emergency Response (PHER) grantees comprised of 62 state, territorial and local health departments. PHER grantees completed an assessment instrument in May 2011, including questions asking them to rate their partnership strength (on a four-point ordinal scale) with six types of partners before and after the H1N1 response. Grantees additionally reported if and how PHER funding contributed to enhancing the strength of these partnerships. RESULTS: Sixty-one PHER grantees (61/62, 98%) completed the assessment instrument's partnerships section. PHER grantees reported that their partnerships with retail pharmacies were most strengthened (mean increase = 1.11 (on a four point ordinal scale), SD = .82). This was followed by schools (K-12) (mean increase = .90, SD = .58); private medical providers (mean increase = .81, SD = .68); immunization authorities (mean increase = .80, SD = .61); main education authorities (mean increase = .75, SD = .68); and businesses (mean increase = .74, SD = .61). Mean PHER grantee increases in the strength of each partner type were statistically significant for all partner types (P < .01). Grantees reported that PHER funding contributed to enhancing the strength of their partnerships with schools most frequently (46/46, 100%), and businesses least frequently (31/37, 83.8%). CONCLUSIONS: This inquiry provides evidence that state, territorial, and local health department partnerships with key sectors, agencies, and programs were strengthened after the H1N1 response. It further demonstrates that the CDC's PHER funding contributed to the health departments' reports of increased partnership strength. PMID- 24229567 TI - Assessment of tissue distribution and concentration of beta-cryptoxanthin in response to varying amounts of dietary beta-cryptoxanthin in the Mongolian gerbil. AB - There is a general lack of knowledge regarding the absorption and tissue storage of the provitamin A carotenoid beta-cryptoxanthin. The present study investigated the whole-body tissue distribution of beta-cryptoxanthin in an appropriate small animal model, the Mongolian gerbil (Meriones unguiculatus), for human provitamin A carotenoid metabolism. After 5 d of carotenoid depletion, five gerbils were euthanised for baseline measurements. The remaining gerbils were placed in three weight-matched treatment groups (n 8). All the groups received 20 MUg/d of beta cryptoxanthin from tangerine concentrate, while the second and third groups received an additional 20 and 40 MUg/d of pure beta-cryptoxanthin (CX40 and CX60), respectively, for 21 d. During the last 2 d of the study, urine and faecal samples of two gerbils from each treatment group were collected. beta Cryptoxanthin was detected in the whole blood, and in twelve of the fourteen tissues analysed. Most tissues resembled the liver, in which the concentrations of beta-cryptoxanthin were significantly higher in the CX60 (17.8 (sem 0.7) MUg/organ; P= 0.004) and CX40 (16.2 (sem 0.9) MUg/organ; P= 0.006) groups than in the CX20 group (13.3 (sem 0.4) MUg/organ). However, in intestinal tissues, the concentrations of beta-cryptoxanthin increased only in the CX60 group. Despite elevated vitamin A concentrations in tissues at baseline due to pre-study diets containing high levels of vitamin A, beta-cryptoxanthin maintained those vitamin A stores. These results indicate that beta-cryptoxanthin is stored in many tissues, potentially suggesting that its functions are widespread. PMID- 24229568 TI - Community psychiatry in the United States 50 years after the Community Mental Health Centers Act. PMID- 24229569 TI - Obesity, mortality, and life years lost associated with breast cancer in nonsmoking US Women, National Health Interview Survey, 1997-2000. AB - INTRODUCTION: The relationship between obesity and breast cancer has been extensively investigated. However, how obesity and breast cancer interplay to affect mortality and life expectancy of women in the United States has not been well studied. METHODS: We used data from the National Health Interview Survey, 1997-2000. Our sample included nonsmoking, nonpregnant women who reported a body mass index of at least 18.5 kg/m(2) and no cancer other than breast cancer at the time of the survey. A survival model with Gamma frailty and Gompertz baseline was used to estimate relative risks of total mortality and project life years lost associated with breast cancer by obesity status and age. RESULTS: Breast cancer increased risk of mortality depending on degree of obesity and decreased life years by 1 to 12 years depending on race, age, and obesity status. Relative risks for death increased with degree of obesity. Obese women under age 50 across all racial groups were predicted to lose the most life years; racial groups other than whites and blacks lost the most life years (11.9 y), followed by whites (9.8 y) and blacks (9.2 y). CONCLUSION: The number of life years lost associated with breast cancer was more marked for more obese than for less obese women and for women under age 50 and women aged 70 or older than for women aged 50 through 69. Public health initiatives should put more emphasis on the prevention and control of obesity for these target populations. PMID- 24229570 TI - Strategies to prevent and reduce diabetes and obesity in Sacramento, California: the African American Leadership Coalition and University of California, Davis. AB - BACKGROUND: Diabetes is one of the leading causes of illness and death for African Americans and people of African descent throughout the United States and in the city and county of Sacramento, California. The involvement of families and communities in developing prevention strategies can increase the likelihood that behavioral changes will be sustained. CONTEXT: Three member organizations of the African American Leadership Coalition (AALC) entered into a partnership with the University of California, Davis (UC Davis) to engage families in developing a process to identify barriers to diabetes and obesity prevention and reduction, exchange strategies, and create action plans for prevention. METHODS: The intervention comprised 3 phases: 1) coalition formation and training; 2) data collection, analysis, and dissemination of results; and 3) development of family and community action plans. Academic and community partners planned and implemented all project phases together. OUTCOMES: Sources of information about diabetes and obesity were primarily doctors and the Internet; barriers were related to lack of time needed to prepare healthy meals, high food costs, transportation to fresh markets, motivation around healthy habits, and unsafe environments. Action plans addressed behavioral change and family cohesion. The group discussion format encouraged mutual support and suggestions for better eating and physical exercise habits. INTERPRETATION: This collaborative partnership model can strengthen existing group relationships or promote new affiliations that form the basis for future action coalitions. Participants worked both within and across groups to exchange information, stories of success and challenges, and specific health improvement strategies. PMID- 24229571 TI - Monetary matched incentives to encourage the purchase of fresh fruits and vegetables at farmers markets in underserved communities. AB - INTRODUCTION: Farmers market programs may increase access to more healthful foods and reduce the high prevalence of obesity in low-income communities. The objective of this study was to examine outcomes of the Fresh Fund farmers market program serving low-income neighborhoods in San Diego, California. METHODS: Through its Farmers Market Fresh Fund Incentive Program, the County of San Diego Health and Human Services Agency offered monetary incentives to government nutrition assistance recipients to purchase fresh produce at 5 farmers markets. Participants enrolled at participating markets from June 1, 2010, through December 31, 2011; they completed baseline and follow-up surveys of daily consumption and weekly spending on fruits and vegetables. We examined enrollment, participation, participant health perceptions, and vendor revenue. RESULTS: During the study period, 7,298 eligible participants enrolled in Fresh Fund; most (82%) had previously never been to a farmers market. Among 252 participants with matched surveys at baseline and 12-month follow-up, the proportion who reported their diet to be "healthy" or "very healthy" increased from 4% to 63% (P < .001); nearly all (93%) stated that Fresh Fund was "important" or "very important" in their decision to shop at the farmers market. Vendors reported that 48% of all market revenue they received was received through the Fresh Fund program. At 2 markets, revenue from June 1, 2011, through January 31, 2012, increased by 74% and 68% compared with revenue from June 1, 2010, through January 31, 2011. CONCLUSION: Participants in the Fresh Fund program self-reported increases in daily consumption and weekly spending on fruits and vegetables, and vendors at participating farmers markets also increased their revenue. PMID- 24229572 TI - Supporting healthful eating through retail environmental change: communities putting prevention to work. PMID- 24229573 TI - Evaluating public health resources: what happens when funding disappears? AB - INTRODUCTION: Although various factors affect the sustainability of public health programs, funding levels can influence many aspects of program continuity. Program evaluation in public health typically does not assess the progress of initiatives after discontinuation of funding. The objective of this study was to describe the effect of funding loss following expiration of a 5-year federal grant awarded to state health departments for development of statewide obesity prevention partnerships. METHODS: The study used qualitative methods involving semistructured key informant interviews with state health departments. Data were analyzed using thematic analysis for effect of funding loss on staffing, programs, partnerships, and implementation of state plans. RESULTS: Many of the programs that continued to run after the grant expired operated at reduced capacity, either reaching fewer people or conducting fewer program activities for the same population. Although many states were able to leverage funding from other sources, this shift in funding source often resulted in priorities changing to meet new funding requirements. Evaluation capacity suffered in all states. Nearly all states reported losing infrastructure and capacity to communicate widely with partners. All states reported a severe or complete loss of their ability to provide training and technical assistance to partners. Despite these reduced capacities, states reported several key resources that facilitated continued work on the state plan. CONCLUSIONS: Decisions regarding continuation of funding are often dependent on budget constraints, evidence of success, and perceived ability to succeed in the future. Evaluating public health funding decisions may help guide development of best practice strategies for supporting long-term program success. PMID- 24229574 TI - Metacercarial polymorphism and genetic variation of Paragonimus heterotremus (Digenea: Paragonimidae), and a re-appraisal of the taxonomic status of Paragonimus pseudoheterotremus. AB - Paragonimus heterotremus, which is an important pathogen for human paragonimiasis in Asia, is recognized as having the smallest metacercariae (maximum diameter < 300 MUm) of any previously reported Paragonimus species. Recently, P. pseudoheterotremus has been described from Thailand as a new species having metacercariae (about 200 MUm) slightly smaller than those of Thai P. heterotremus. In fact, the small size of P. pseudoheterotremus metacercariae is compatible with those of P. heterotremus from India and China. In this study in Vietnam, we found variably sized small metacercariae which are expected to consist of both P. heterotremus and P. pseudoheterotremus. Contrary to expectation, the adult flukes obtained by separate infection of experimental cats with different sized metacercariae were all identified as P. heterotremus, using both morphological and molecular characteristics. The molecular analyses of an extensive collection of P. heterotremus/P. pseudoheterotremus isolates from Asian countries also indicated that genetic distances between different populations of P. heterotremus are even larger than that between P. pseudoheterotremus and P. heterotremus. The haplotype network showed that all P. heterotremus and P. pseudoheterotremus isolates formed a P. heterotremus complex consisting of three groups with strong geographical origins. In addition, the Indian P. heterotremus group is the root of the other P. heterotremus and P. pseudoheterotremus populations. Based on the observed metacercarial polymorphisms and genetic variation in P. heterotremus, P. pseudoheterotremus should be considered a geographically isolated population of the P. heterotremus complex. PMID- 24229575 TI - Production and perception of listener-oriented clear speech in child language. AB - In this paper, we ask whether children are sensitive to the needs of their interlocutor, and, if so, whether they - like adults - modify acoustic characteristics of their speech as part of a communicative goal. In a production task, preschoolers participated in a word learning task that favored the use of clear speech. Children produced vowels that were longer, more intense, more dispersed in the vowel space, and had a more expanded F0 range than normal speech. Two perception studies with adults showed that these acoustic differences were perceptible and were used to distinguish normal and clear speech styles. We conclude that preschoolers are sensitive to aspects of the speaker-hearer relationship calling upon them to modify their speech in ways that benefit their listener. PMID- 24229576 TI - The effect of chronic pain intensity on the stability limits in patients with low back pain. AB - OBJECTIVE: The purpose of this study was to evaluate if the intensity of recurrent chronic pain would modify postural performance in reaching the functional limits of stability (LOS) in chronic low back pain (CLBP) patients. METHODS: Three groups of subjects were investigated. Healthy persons comprised the asymptomatic group (n = 32) while CLBP patients (n = 36) were divided into 2 subgroups, according to the reported intensity of resting pain on a numerical rating scale: patients with low (LP) and high pain (HP) levels. The maximal displacement of the center of pressure (COP) indexing the LOS magnitude and the COP mean velocity indexing the performance in reaching LOS were calculated on a Kistler force plate during forward and backward voluntary body lean with eyes open (EO) or closed (EC). RESULTS: The forward LOS was lower in both the LP (P < .01) and HP (P < .01) subgroups than in the asymptomatic under EO and EC conditions, while no differences between the LP and HP groups were found. The backward LOS was lower in the HP group than in asymptomatic but only with EC (P = .01). Eye closure caused an increase in forward (P = .02) and backward (P = .001) COP velocity in the LP group and forward COP velocity in the asymptomatic (P = .04) only. With EC, the only intergroup difference was lower forward COP velocity in the HP than LP group (P = .04). CONCLUSION: Subjects with CLBP had reduced forward LOS regardless the pain level. However, the higher level of pain was associated with slower execution of voluntary leaning tasks, with EC only. PMID- 24229577 TI - Fifty years of progress in community mental health in US: the growth of evidence based practices. AB - Fifty years have elapsed since the passage of the Community Mental Health Centers (CMHC) Act in 1963 that reflected the legislative peak of the community mental healthcare movement in the US Progress of the last 10 years is represented both by expansions of evidence-based practices (EBPs) and the development of emerging practices and fundamental shifts in the orientation of the system stimulated by the consumer-driven recovery movement. Established EBPs have accumulated expanded evidence, new EBPs have been developed and emerging EBPs are gaining increased acceptance. While the lack of widespread implementation of EBPs as well as the limitations of these technologies produces unnecessary suffering and disability, we believe that the growth of evidence for treatments and services justifies optimism for the future. PMID- 24229578 TI - Induced reproduction and early development histology of Oscar Astronotus ocellatus (Agassiz, 1831). AB - Oscar (Astronotus ocellatus) is an important fish from the Amazon Basin that has great potential for fish farming, human consumption, sport fishing and fish keeping. This study aimed to evaluate the effect of two hormonal treatments on the induction of artificial reproduction in broodstock and to describe the histological development of embryos and larvae. Broodstocks were selected and induced using two different hormones: (i) extract of carp pituitary (ECP); and (ii) synthetic human chorionic gonadotropin (hCG). Spawnings were transferred to hatcheries, collected at pre-established times, processed and analysed by histology. Astronotus ocellatus did not respond well to induced reproduction. From 16 couples of breeding fish, only five out of the eight females released oocytes after the hormonal action time, three with hCG and two with ECP; just one male responded positively to hCG. Oscar eggs were oval, and semi-adhesive, the yolk contained granules, and egg diameter was approximately 1.65 +/- 0.057 to 1.98 +/- 0.038 mm. Development from the initial collection (IC) point until the total absorption of the yolk lasted 315 h, at an average temperature of 27.45 +/- 2.13 degrees C. Several events marked embryonic and larval development, including the formation of the optic cup, forebrain, otic vesicle and cephalic divisions. The newly hatched larvae had non-pigmented eyes, and a closed mouth and anus, as well as the presence of adhesive glands on the head. Larval development was characterized by formation of the heart, liver, gaseous bladder, gills, pronephros, brain, fins and also the digestive tract. These results provide important information for the rearing and reproduction of A. ocellatus. PMID- 24229579 TI - Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort. AB - Fat-soluble vitamins A, E and K have been shown to play roles in immunity and inflammation, but studies on child allergic disease have been few and inconsistent. The aim of the present study was to examine the relationship between maternal intake of vitamins A, E and K in mid-pregnancy and child asthma and allergic rhinitis. We used data on 44 594 mother-child pairs from the Danish National Birth Cohort. Maternal intake of fat-soluble vitamins was calculated based on the information from a validated FFQ completed in mid-pregnancy. At 18 months, interviews with the mothers were conducted to evaluate doctor-diagnosed child asthma. At age 7 years, we assessed child asthma and allergic rhinitis using questions from the International Study of Asthma and Allergies in Childhood questionnaire and by national registries on hospital contacts and medication use. Current asthma was defined as asthma diagnosis and wheeze in the past 12 months by maternal report. We calculated multivariable risk ratios and 95 % CI by comparing the highest v. lowest quintile (Q) of maternal vitamin A, E and K intake in relation to child allergic disease outcomes. Maternal total vitamin K intake was directly associated with ever admitted asthma (Q5 v. Q1: 1.23, 95 % CI 1.01, 1.50) and current asthma at 7 years (Q5 v. Q1: 1.30, 95 % CI 0.99, 1.70). Weak inverse associations were present for maternal vitamin A and E intake during pregnancy with child allergic rhinitis. Maternal vitamin K intake during pregnancy may increase the risk of child asthma, and should be explored further on a mechanistic level. Conversely, maternal vitamin A and E intake may protect against child allergic rhinitis. PMID- 24229580 TI - Medical ethics versus governmental objectives. PMID- 24229581 TI - [Rickets-like genetic diseases]. AB - This paper summarizes the clinical features, causative genes and treatment progress of patients with rickets-like genetic diseases, including X-linked hypophosphatemic rickets (XLH), hypophosphatasia, achondroplasia, vitamin D dependent rickets, pycnodysostosis and ectodermal dysplasia, who visited the pediatric or child health clinic due to the symptoms of rickets, including bow legs, delayed closure of the anterior fontanelle, and sparse hair. Children with XLH usually go to hospital for bow legs and short stature, and biochemical evaluation reveals significantly low serum phosphorus so it is easily diagnosed. This disease is treated using phosphate mixture and 1,25(OH)2D3, which is different from the treatment of nutritional vitamin D deficiency rickets. Hypophosphatasia is characterized by a significant decrease in serum alkaline phosphatase, as well as normal serum calcium and phosphorus. The disease is caused by mutations in TNSALP gene. Patients with achondroplasia show short limbed dwarfism and special face in addition to bow legs, but with normal serum calcium, phosphorus and alkaline phosphatase. Bone X-ray and FGFR3 gene test contribute to the diagnosis. Vitamin D-dependent rickets is an autosomal recessive disease, and active vitamin D supplement is effective in treatment of the disease. Patients with pycnodysostosis may be first seen at hospital because of large anterior fontanelle; in addition, they also show obtuse mandibular angle, dental abnormalities and dysplastic nails, which are caused by mutations in TSK gene. Children with ectodermal dysplasia may see a doctor for sparse hair, and they are easily misdiagnosed with nutritional vitamin D deficiency rickets. Ectodermal dysplasia is related to EDA, EDAR, EDARADD and WNT 10A genes. PMID- 24229582 TI - [Gene mutation analysis of X-linked hypophosphatemic rickets]. AB - OBJECTIVE: To investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype. METHODS: Clinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated. RESULTS: PHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000). CONCLUSIONS: Missense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH. PMID- 24229583 TI - [Clinical analysis and genetic diagnosis of short-limb inherited short stature diseases in children]. AB - OBJECTIVE: To analyze the clinical manifestations, bone X-ray findings and genetic analysis results of three short-limb inherited short stature diseases: achondroplasia (ACH), hypochondroplasia (HCH) and pseudoachondroplasia (PSACH). METHODS: The clinical manifestations, bone X-ray findings, and genetic analysis results of 10 children with genetically confirmed short-limb inherited short stature diseases, including 4 cases of ACH 3 cases of HCH, and 3 cases of PSACH, were analyzed. RESULTS: The 10 patients had a mean body height of -3.69+/-1.79 SD, a mean sitting height/standing height ratio of 0.65+/-0.03, and a mean finger spacing/body height ratio of 0.93+/-0.04. Four ACH cases and 3 PSACH cases showed typical bone X-ray findings; one HCH case showed a smaller sciatic notch, and another HCH case showed no widening of interpedicular distance. G380R mutation in FGFR3 gene was detected in 3 of 4 ACH cases, and Y278C mutation in the other ACH case, N540K mutation in FGFR3 gene was detected in 3 HCH cases, and heterozygous mutations in COMP gene were detected in 3 PSACH cases. CONCLUSIONS: Children with ACH and PSACH have severer short stature and skeletal deformities than children with HCH, who have mild, atypical clinical manifestations. Bone X-ray and genetic analysis are helpful for the diagnosis and differential diagnosis of the three diseases. The mutational hotspots in two genes are involved in the three diseases, which is conducive to clinical genetic diagnosis. PMID- 24229584 TI - [Clinical features and COMP gene mutation in a family with a pseudoachondroplasia child]. AB - This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH. PMID- 24229585 TI - [Analysis of CYP21A2 gene mutation in one case of congenital adrenal hyperplasia]. AB - CYP21A2 gene mutations in a child with congenital adrenal hyperplasia (CAH), and the child's parents, were detected in the study. The clinical features, treatment monitoring and molecular genetic mechanism of CAH are reviewed. In the study, DNA was extracted from peripheral blood samples using the QIAGEN Blood DNA Mini Kit; a highly specific PCR primer for CYP21A2 gene was designed according to the sequence difference between CYP2lA2 gene and its pseudogene; the whole CYP2lA2 gene was amplified with PrimeSTAR DNA polymerase (Takara), and the amplification product was directly sequenced to detect and analyze CYP2lA2 gene mutation. The child was clinically diagnosed with CAH (21-hydroxylase deficiency, 21-OHD) at the age of 36 days, and the case was confirmed by genetic diagnosis at the age of 1.5 years. The proband had a homozygous mutation at c.293-13C in the second intron of CYP21 gene, while the parents had heterozygous mutations. Early diagnosis and standard treatment of CAH (21-OHD) should be performed to prevent salt-wasting crisis and reduce mortality; bone aging should be avoided to increase final adult height (FAH), and reproductive dysfunction due to oligospermia in adulthood should be avoided. These factors are helpful for improving prognosis and increasing FAH. Investigating the molecular genetic mechanism of CAH can improve recognition and optimize diagnosis of this disease. In addition, carrier diagnosis and genetic counseling for the proband family are of great significance. PMID- 24229586 TI - [Clinical effect of stem cell transplantation via hepatic artery in the treatment of type II hyperammonemia: a report on 6 cases]. AB - This study aimed to investigate the clinical effect of transplantation of CD133+ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133+ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133+ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 MUmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent. PMID- 24229587 TI - [Advances in clinical and molecular genetics studies on argininemia]. AB - Argininemia is a rare, autosomal recessive, metabolic disorder caused by an hereditary deficiency of hepatocytes arginase due to ARG1 gene defect. Arginase is the final enzyme in the urea cycle, catalyzing the hydrolysis of arginine to ornithine and urea. Research advances in the clinical manifestations, diagnosis, treatment, prenatal diagnosis and genetics of argininemia were reviewed in this paper. The clinical manifestations of patients with argininemia are complicated and nonspecific so that clinical diagnosis is usually difficult and delayed. Progressive spastic tetraplegia, seizures and cerebella atrophy are common clinical features of the disease. Blood amino acids analysis, arginase assay and ARG1 gene analysis are important to the diagnosis of argininemia. Early diagnosis and a protein-restricted diet with citrulline and benzoate supplements can contribute a lot to improve patient prognosis. With the application of liquid chromatography-tandem mass spectrometry in selective screening and newborn screening for inborn errors of metabolism, an ever-increasing number of patients with argininemia are detected at the asymptomatic or early stages. PMID- 24229588 TI - [Advanced molecular technologies for the diagnosis of congenital malformation in neonates]. AB - Congenital malformation is one of the most frequent causes of infant death in western countries and major cities in China. Though genetic screening of newborns remains a hot issue and concern, the mortality rate associated with birth defects has not been significantly reduced over the past 20 years. Many genetic diseases manifest symptoms during the first 28 days of life, but full clinical symptoms might not be evident in newborns. Moreover, genetic aberrations is highly heterogeneous. These complicated factors lead to the establishment of diagnosis based on nonspecific or obscure symptoms. Recently developed array comparative genomic hybridization (CGH) and next generation sequencing (NGS) techniques with efficient high-resolution allow to screening of the entire genome for DNA copy number variants and sequencing respectively. These new and powerful tools can shorten the differential diagnosis process and quicken to movement towards targeted treatment and genetic and prognostic counseling. PMID- 24229589 TI - [Research advances in molecular genetics and treatment of familial hemophagocytic lymphohistiocytosis]. AB - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by pancytopenia and multiple organ infiltrations of lymphocytes and histiocytes with proliferation and hemohpagocytic activity. HLH is classified as primary (or familial) and secondary. Familial HLH is common in infants and young children, and is related to genetic defects. This article aims to review research advances on PRF1, UNC13D, STX11 and STXBP2, as well as the other 5 genes associated with familial HLH based on molecular genetics, and to summarize diagnosis and treatment methods for this disease. PMID- 24229590 TI - [Pediatric Shwachman-diamond syndrome: report on 5 cases and literature review]. PMID- 24229591 TI - [A case report of rare bardet-biedl syndrome]. PMID- 24229592 TI - [A case report of Crouzon syndrome with short status]. PMID- 24229593 TI - [Epidemiological analysis of childhood asthma in Yichang City, China]. AB - OBJECTIVE: To study the prevalence, epidemiological characteristics, and risk factors for childhood asthma in Yichang City, China and to collect evidence for the early diagnosis and preventive treatment of asthma. METHODS: Preliminary screening questionnaires were distributed to more than 90% of children in 5 kindergartens, 10 primary and secondary schools, and 5 communities in Yichang City to detect children with suspected asthma. These surveyed children were selected by cluster random sampling. A further questionnaire survey was conducted for suspected cases. Meanwhile, a similar number of sex- and age-matched non asthmatic children were selected for the case-control study. Information from returned questionnaires was entered into a database for statistical analysis. RESULTS: A total of 11 000 questionnaires were distributed, and 10 456 (95.1%) questionnaires were returned. The prevalence rate of asthma among children in Yichang was 3.47%, significantly higher in boys than in girls (P<0.05). A total of 107 out of 363 children with asthma had a history of drug allergy, and 152 cases had a family history of allergy. The majority of asthmatic children had irregular onset-prone seasons and hours. Respiratory tract infections were the most common trigger of asthma attacks, accounting for 93.1% of all onsets; family history of allergy, history of early use of antibiotics, history of housing renovation, and history of passive smoking were the major risk factors for asthma. CONCLUSIONS: Prevention of respiratory tract infections may reduce the frequency of asthma attacks; reducing the use of antibiotics during early childhood, decreasing the frequency of housing renovation, and advocating for smoking cessation among parents have preventive effects on asthma. PMID- 24229594 TI - [Association between body mass index and lung function in children with asthma after corticosteroids inhalation]. AB - OBJECTIVE: To study the association between body mass index (BMI) and lung function of asthmatic children after inhaling corticosteroids (ICS). METHODS: One hundred and fifty-seven children with asthma were classified into obese (46 cases), over-weight (50 cases) and normal-weight groups (61 cases) based on BMI. All of the children received ICS for one year. Pulmonary functions were evaluated before and after treatment. Large airway function includes forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%). Small airway function includes maximal expiratory flow 25 (MEF25%) and maximal expiratory flow 50 (MEF50%). RESULTS: The bronchial provocation test before treatment showed that the decline rate of pulmonary function (FVC%, FEV1%, MEF25% and MEF50%) in the obese group was higher than the normal-weight group after methacholine inhalation. After salbutamol inhalation, the improvement rate of the large airway (FVC%) and small airway (MEF25% and MEF50%) functions in the obese group was lower than the normal-weight group, and the improvement rate of small airway (MEF25% and MEF50%) function in the over-weight group was lower than in the normal-weight group. After treatment with ICS for one year, large airway function (FVC% and FEV1%) in the normal-weight group was higher than pre-treatment, however only FVC% in the normal-weight and obese groups was higher than pre treatment. There was no significant difference in small airway function before and after treatment in all three groups. CONCLUSIONS: Obesity can increase the sensitivity to methacholine and restrain the sensitivity to tosalbutamol in children with asthma. ICS can improve the large airway function in asthmatic children with normal body weight, but has no effect on small airway function. Obesity can restrain the effect of ICS on asthmatic children. PMID- 24229595 TI - [Determination and clinical significance of serum surfactant proteins A and D in children with bronchiolitis]. AB - OBJECTIVE: To study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis. METHODS: Seventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group. RESULTS: The acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01). CONCLUSIONS: Serum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children. PMID- 24229596 TI - [Comparison of clinical features and co-infection between pneumonia caused by influenza virus A and pneumonia caused by influenza virus B among children]. AB - OBJECTIVE: To compare the clinical features and co-infection between pneumonia caused by influenza virus A (IVA) and pneumonia caused by influenza virus B (IVB) among children. METHODS: A total of 165 children with pneumonia caused by influenza virus (IV) were included in the study. These subjects were divided into IVA(n=71) and IVB pneumonia groups (n=94) according to the subtypes of IV. The IVA pneumonia group was further divided into simple infection (n=14) and co infection subgroups (n=57), and the IVB pneumonia group was also further divided into simple infection (n=27) and co-infection subgroups (n=67). Co-infection rate and pathogen spectrum were analysed in children with IV pneumonia. RESULTS: The IVB pneumonia group had significantly increased mean age of onset and significantly prolonged mean duration of fever compared with the IVA pneumonia group (P<0.05). Co-infection rate among children with IV pneumonia was 75.2%, who were co-infected with bacteria (44.2%), Mycoplasma pneumoniae (MP, 21.8%) and other viruses (45.5%). Respiratory syncytial virus (RSV) was most common in children co-infected viruses (89% ). The rate of co-infection with RSV was significantly higher in the IVA pneumonia group than in the IVB pneumonia group. There were no significant differences in age, length of hospital stay, duration of fever, percentage of neutrophils, prealbumin, C-reactive protein, alanine aminotransferase, and creatine kinase-MB between the simple infection and co infection subgroups of each group. CONCLUSIONS: Children with IVB pneumonia have prolonged duration of fever and increased age of onset compared with those with IVA pneumonia. Co-infection rate is high among children with IV pneumonia, who may be co-infected with bacteria, viruses and MP. Co-infection with RSV is more common in children with IVA pneumonia. It is difficult to identify the presense of co-infection using clinical indices. PMID- 24229597 TI - [Clinical characteristics of children with Streptococcus pneumoniae septicemia and drug sensitivity of Streptococcus pneumoniae]. AB - OBJECTIVE: To study the clinical characteristics of children who suffered from Streptococcus pneumoniae (SP) septicemia and the drug sensitivity of SP strains. METHODS: A retrospective analysis was performed on the clinical data of 25 children with SP septicemia between January 2009 and December 2012. RESULTS: Of the 25 cases, 16 (64%) were aged under 2 years, 5 (20%) were aged 2-5 years, and 4 (16%) were aged over 5 years. Fourteen cases (56%) were complicated by infection of other organs, and 5 cases (20%) had underlying chronic diseases. Fever was the most common clinical manifestation, and the majority presented with remittent fever. Eight patients with pneumonia or pyothorax had pulmonary symptoms. Five patients with purulent meningitis had neurological symptoms, five cases had hepatosplenomegaly and two cases had septic shock. Nineteen cases (76%, 19/25) had significantly elevated white blood cell (WBC) counts, twenty-one cases (84%, 21/25) had significantly elevated serum C-reactive protein (CRP) levels, and eight cases (50%, 8/16) had significantly elevated serum procalcitonin (PCT) levels. The drug sensitivity analysis showed that invasive SP had high resistance rates to penicillin (96%), clindamycin hydrochloride (88%) and erythromycin (84%), and it was completely sensitive to imipenem, vancomycin, levofloxacin and linezolid. The multi-drug resistance rate of invasive SP was up to 88%. Twenty three cases (92%) were cured or improved after active treatment. CONCLUSIONS: SP septicemia is commonly seen in children aged under 2 years. The most common clinical manifestation is fever, accompanied by elevated WBC count, CRP level and PCT level, and it is usually complicated by pulmonary or brain infection. Resistance to multiple antibiotics is very common in SP strains, so it is important to properly use antibiotics according to drug sensitivity test results. Patients who receive active treatment have a good clinical outcome. PMID- 24229598 TI - [Therapeutic effect of probiotics and oral IgY as supplementary drugs in the treatment of pediatric rotavirus enteritis: a comparative study]. AB - OBJECTIVE: To compare the therapeutic effect of probiotics and oral immunoglobulin on pediatric rotavirus enteritis. METHODS: A randomized, controlled trial was conducted in 150 children with rotavirus enteritis who were randomly divided into control, probiotic and immunoglobulin groups (n=50 each). In addition to basic treatment, the control group was given placebo, the probiotic group was given live combined bifidobacterium and lactobacillus tablets, and the immunoglobulin group was orally given anti-rotavirus egg yolk immunoglobulin (IgY). Clinical symptoms such as stool frequency and stool properties were recorded every day. Fresh stool samples were collected on days 1, 3, 5, 7, 9 and 11 of treatment. Intestinal flora imbalance was detected and divided into three degrees by microscopic examination of stool. Fecal SIgA level and fecal rotavirus shedding were measured by radioimmunoassay and double antibody sandwich ELISA respectively. RESULTS: Compared with the control group, the probiotic group had reduced intestinal flora imbalance, decreased stool frequency, and reduced incidence of secondary intestinal bacterial infection after 3 days of treatment (P<0.05). There was no significant difference in disease course between the probiotic and control groups. Compared with the control group, the immunoglobulin group had a significantly increased fecal SIgA level after 1 day of treatment (P<0.05), significantly decreased frequency of diarrhea and fecal rotavirus shedding after 3 days of treatment (P<0.05), and a significantly shorter disease course (4.5+/-1.0 vs 5.8+/-1.7 days; P<0.05). CONCLUSIONS: For children with rotavirus enteritis, probiotics can reduce intestinal flora imbalance and prevent secondary intestinal bacterial infection, but probiotics take a long time to relieve clinical symptoms and cannot shorten the course of disease. Oral immunoglobulin takes effect quickly and can rapidly eliminate rotavirus, promote the production of SIgA, and shorten the course of disease. PMID- 24229599 TI - [Association between vitamin D receptor gene polymorphisms and pediatric Crohn's disease in China: a study based on gene sequencing]. AB - OBJECTIVE: To investigate the association between TaqI, BsmI, and ApaI polymorphisms of vitamin D receptor (VDR) gene and pediatric Crohn's disease (CD) in China. METHODS: Nineteen children with CD were selected as a case group, and 122 healthy children who underwent physical examination were selected as a control group. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels were measured using ELISA. The TaqI, BsmI, and ApaI polymorphisms of VDR gene were determined by gene sequencing, and the two groups were compared in terms of genotype and allele frequencies. RESULTS: The case group had significantly lower serum 25(OH)D3 levels than the control group (17.3+/-2.4 ng/mL vs 26.9+/-2.1 ng/mL; P<0.05). There were no significant differences in the frequencies of genotypes and alleles of TaqI, BsmI, and ApaI polymorphisms between the case and control groups (P>0.05). CONCLUSIONS: Children with CD have low serum 25(OH)D3 levels. TaqI, BsmI, and ApaI polymorphisms of VDR gene may not be associated with susceptibility to CD among the Chinese population. PMID- 24229600 TI - [Clinical significance of serum levels of IGF-1 and IGFBP-3 in children with Henoch-Schonlein purpura or Henoch-Schonlein purpura nephritis]. AB - OBJECTIVE: To study the clinical significance of serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP 3) in children with Henoch-Schonlein purpura (HSP) or Henoch-Schonlein purpura nephritis (HSPN). METHODS: Thirty-one children with HSP were selected as the HSP group, and 28 children with HSPN were selected as the HSPN group. Another 31 healthy children were selected as the control group. ELISA was used to measure serum levels of IGF-1 and IGFBP-3 in each group. Measurement of 24-hour urinary protein excretion was performed using an automatic biochemical analyzer in the HSPN group. Serum immunoglobulin (Ig) levels, complement C3 level and complete blood counts in each group were determined, and urine analysis was also performed. RESULTS: Serum levels of IGF-1 and IGFBP-3 in the HSP group were significantly higher than in the control group (P<0.05), and serum levels of IGF 1 and IGFBP-3 in the HSPN group were significantly higher than in the HSP and control groups (P<0.05). Among 12 children who underwent renal puncture biopsy, patients with higher pathological grades had higher serum levels of IGF-1 and IGFBP-3. In children with HSPN, those with proteinuria had significantly higher serum levels of IGF-1 and IGFBP-3 than those without proteinuria (P<0.05). Levels of white cells, red cells, platelet count, complement C3, IgG, and IgA and IgA/C3 ratio were significantly higher in the HSP and HSPN groups than in the control group (P<0.05). CONCLUSIONS: Increased serum levels of IGF-1 and IGFBP-3 are observed in the acute onset period of HSP, which may be related to the degree of proteinuria and renal damage. Serum levels of IGF-1 and IGFBP-3 may be indicators of renal involvement. PMID- 24229601 TI - [Significance of Tp-Te interval for risk stratification of ventricular premature contractions in children]. AB - OBJECTIVE: To investigate the significance of Tp-Te interval for risk stratification of ventricular premature contractions (VPC) in children. METHODS: A total of 120 children with VPC were divided into benign VPC (n=40), organic disease (n=40) and ventricular parasystole groups (n=40) according to the etiology of VPC; another 40 children who underwent physical examination were selected as the normal control group. The four groups were compared in terms of Tp-Te intervals and Tp-Te/QT ratios in leads V3, V4 and V5. RESULTS: The Tp-Te interval in lead V3 was significantly longer in the organic disease group than in the other groups (P<0.05), the benign VPC group had a significantly shorter Tp-Te interval in lead V4 than the normal control and organic disease groups (P<0.05), and the organic disease group had a significantly longer Tp-Te interval in lead V5 than the benign VPC group (P<0.05). The Tp-Te/QT ratios in leads V3-V5 were significantly higher in the organic disease group than in the other groups (P<0.05). The Tp-Te/QT ratios in leads V4 and V5 showed significant differences between the ventricular parasystole and benign VPC groups (P<0.05). CONCLUSIONS: Tp-Te interval is susceptible to changes in heart rate, and it is of little value for the risk stratification of VPC in children. Tp-Te/QT ratio, however, may be used as an important non-invasive index for clinical risk stratification of VPC in children and is worthy of further study. PMID- 24229602 TI - [Effect of Mycobacterium phlei F.U.36 on balance of CD4+CD25+ regulatory T cells and Th17 cells in asthmatic mice]. AB - OBJECTIVE: To evaluate the effect of early intervention with Mycobacterium phlei F.U.36 injection on the balance of CD4+CD25+ regulatory T cells and Th17 cells in asthmatic mice, and to investigate the immunomodulatory effect of Mycobacterium phlei F.U.36. METHODS: Thirty female BALB/c mice were randomly divided into three groups: normal control (n=10), asthma model (n=10) and Mycobacterium phlei F.U.36 treatment groups (n=10). A mouse model of asthma was prepared by injection and aerosol inhalation of chicken ovalbumin in the asthma model and Mycobacterium phlei F.U.36 treatment groups, while mice in the normal control group were given normal saline instead. The treatment group was intraperitoneally injected with Mycobacterium phlei F.U.36 (0.57 MUg, once every other day) three times in the first two weeks after the first sensitization. All mice were sacrificed at 24 hours after the last challenge. Left lung tissues of these mice were obtained and made into sections for observation of inflammatory changes. The percentages of CD4+CD25+ regulatory T cells and Th17 cells in CD4+ T cells among splenic mononuclear cells were determined by flow cytometry. The levels of interleukin (IL)-10 and IL-17 in serum and bronchoalveolar lavage fluid were measured using ELISA. RESULTS: Compared with the normal control group, the asthma model group had significantly decreased percentages of CD4+CD25+ regulatory T cells and IL-10 levels (P<0.05) and significantly increased percentages of Th17 cells and IL-17 levels (P<0.05). Compared with the asthma model group, the Mycobacterium phlei F.U.36 treatment group had significantly increased percentages of CD4+CD25+ regulatory T cells and IL-10 levels (P<0.05) and significantly decreased percentage of Th17 cells and IL-17 levels (P<0.05). CONCLUSIONS: Early intervention with Mycobacterium phlei F.U.36 can promote development of CD4+CD25+ regulatory T cells and production of IL-10 and inhibit generation of Th17 cells and production of IL-17 in asthmatic mice. PMID- 24229603 TI - [Role of the FOXO3a transcription factor in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage]. AB - OBJECTIVE: To explore the role and mechanisms of FOXO3a nuclear translocation in neuronal apoptosis after hypoxia-ischemia (HI). METHODS: One hundred and sixty 10 day-old Sprague-Dawly rats were randomly divided into two groups: HI and sham operated. The right common carotid artery was ligated followed by hypoxia exposure for 2.5 hours in the HI group. The sham-operated group rats were not subjected to carotid artery ligation or hypoxia treatment. Rat cerebral cortex was collected at 0.5, 2, 4, 8 and 24 hours after hypoxia. Western blot was used to detect expression of total FOXO3a protein, pnuclear and cytoplasmic FOXO3a and Bim. TUNEL staining was used to detect apoptotic cells. RESULTS: The nuclear protein of FOXO3a obviously increased from 0.5 to 24 hours after HI in a time dependent manner compared with the sham-operated group (P<0.01). On the contrary, cytoplasmic protein evidently decreased from 0.5 to 24 hours in the HI group compared with the sham-operated group (P<0.01). Bim protein increased from 0.5 hour, peaked at 2 hours, started to decline at 4 hours (P<0.01), and returned to baseline level at 8 and 24 hours after HI in the HI group compared with the sham operated group. TUNEL positive cells started to express at 4 hours, and peaked at 24 hours after HI (P<0.01). However, TUNEL positive cells were rarely found in the sham-operated group. CONCLUSIONS: HI induces FOXO3a translocation from cytoplasm to nucleus, and enhances protein expression of its target gene Bim in the neonatal rat brain. The upregulation of Bim expression might be related to neuronal apoptosis. PMID- 24229604 TI - [Gastrointestinal symptoms in children with Henoch-Schonlein purpura]. PMID- 24229605 TI - [Intractable pulmonary edema and bulbar paralysis caused by severe hand-foot mouth disease: a case report]. PMID- 24229606 TI - [Research advances on CIDEC in insulin resistance]. AB - Childhood obesity has been rising dramatically in recent years and most patients are insulin resistant. Recent studies have indicated that cell death-inducing DFF45-like effector C (CIDEC) is responsible for the development of insulin resistance. CIDEC regulates adipogenesis, lipid storage and lipolysis, thus protecting insulin target tissues from lipotoxity. This paper reviews current findings on the structure and function of CIDEC, its transcriptional and post translational regulations, and the underlying mechanism of CIDEC causing insulin resistance. As a novel lipid droplet protein, CIDEC may be a drug target for treatment of insulin resistance and relevant metabolic disorders. PMID- 24229607 TI - Glutamine modulates acute dextran sulphate sodium-induced changes in small intestinal intraepithelial gammadelta-T-lymphocyte expression in mice. AB - The present study investigated the effect of glutamine (Gln) on dextran sulphate sodium (DSS)-induced changes in the expression of small-intestinal intraepithelial lymphocyte (IEL) gammadelta-T cells in mice. Mice were randomly assigned to a normal control (NC) group and two DSS-treated groups. The NC group and one of the DSS-treated groups (DSS-C) were fed a common semi-purified diet, while the other DSS-treated group (DSS-G) was fed an identical diet, except that part of casein was replaced by Gln, which provided 25 % of total amino acid nitrogen. After being fed the diets for 10 d, mice in the NC group were given distilled water, while the DSS-treated groups were given distilled water containing 2.5 % DSS for 5 d. At the end of the experiment, the mice were killed. The small-intestinal IEL gammadelta-T-cell subset was isolated for further analysis. The results indicated that DSS treatment resulted in a lower percentage of small-intestinal IEL gammadelta-T cells and higher mRNA expressions of interferon-gamma, TNF-alpha, IL-17, complement 5a receptor and keratinocyte growth factor in IEL gammadelta-T cells. Gln administration increased the proportion of small-intestinal IEL gammadelta-T cells, and the expression levels of immunomodulatory mediator genes in IEL gammadelta-T cells were lower in the DSS-treated mice. The histological findings indicated that the immunoreactive intensity of the tight junction protein ZO-1 in the small-intestinal mucosa was higher in the DSS-G group than in the DSS-C group. These results indicate that pretreatment with Gln increases the proportion of small-intestinal IEL gammadelta T cells and down-regulates gammadelta-T-cell-expressed inflammatory mediators, which may consequently ameliorate the severity of DSS-induced small-intestinal epithelial injury. PMID- 24229608 TI - Mental health reform under policy mainstreaming: needed, but uncertain. AB - October 2013 marks the 50th anniversary of President John F. Kennedy's message to the US Congress on the need to reform mental healthcare. Much has changed in that time. In 2006, Frank and Glied summarized these changes and the forces behind them, finding that the well-being of people with mental illness was 'better but not well.' They also conclude that most improvements have been due to 'mainstreaming,' the inclusion of those with mental illness in broad reforms such as Medicare, Medicaid and Social Security. With the gradual assimilation of mental health concerns, leadership and resources into mainstream programmes and agencies, future improvements will require that these programmes are accessible and oriented to people with mental illness. The passage of broad health reform legislation in 2010 (the Affordable Care Act) reinforces this change; several of its provisions attempt to make healthcare more relevant to the population with mental illness. In this editorial, I discuss a set of challenges which remain for the population with mental illness in the healthcare system, and the prospects for change. These challenges include: (1) improving basic mental healthcare in primary care, (2) improving mental healthcare for children, (3) earlier detection and treatment of psychotic illness, (4) disability and unemployment and (5) the challenge of sustaining an adequate, speciality public mental healthcare system under conditions of mainstreaming. In general, I conclude that the prospects for successful reform are uncertain. Establishing mental healthcare specialization in mainstream systems has not been notably successful to date. PMID- 24229609 TI - An audit of 'dead ear' after ear surgery. AB - INTRODUCTION: 'Dead ear' is a rare and serious complication of ear surgery. This paper presents an audit of this complication. METHOD: Over 6 years, data for all 617 middle-ear operations performed under the care of a single consultant were recorded for the International Otology Audit. All cases of dead ear were identified and assessed. RESULTS: A post-operative dead ear occurred in 6 cases (approximately 1 per cent). No cases of post-operative dead ear occurred following the 83 otosclerosis operations and the 62 children's procedures. Amongst 187 adult patients undergoing mastoid surgery for cholesteatoma, there were 5 cases of post-operative dead ear (2.7 per cent of cases). CONCLUSION: The occurrence of dead ear after cholesteatoma surgery in adults is less rare than previously thought. This has implications for the surgical consenting process. The current series suggests that, whilst dead ear is often avoidable, it is sometimes inevitable. PMID- 24229610 TI - Pseudomonas aeruginosa dose response and bathing water infection. AB - Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management. PMID- 24229611 TI - Early development of Betta splendens under stereomicroscopy and scanning electron microscopy. AB - Betta splendens is a very important ornamental species. The current paper describes the embryonic and larval development of B. splendens under stereomicroscopy and scanning electron microscopy. Eggs and larvae from natural spawning were collected at different developmental stages at previously established intervals and analysed. The eggs of B. splendens are yellowish, clear, spherical, demersal, translucent and telolecithal with a large amount of yolk. Between 0-2 h post-initial collection (hpIC), the eggs were at the egg cell, first cleavage and morula stages. The blastula stage was identified at 2-3 hpIC and the early gastrula phase was observed at 3-4 hpIC with 20% epiboly, which was finalized after 13-18 hpIC. When the pre-larvae were ready to hatch, the appearance of somites and the free tail were observed, at 23-25 hpIC. At 29 hpIC, the majority of larvae had already hatched at an average temperature of 28.4 +/- 0.2 degrees C. The newly hatched larvae measured 2.47 +/- 0.044 mm total length. The mouth opened at 23 h post-hatching (hPH) and the yolk sac was totally absorbed at 73 hPH. After 156 hPH, the heart was pumping blood throughout the entire larval body. The caudal fin, operculum and eyes were well developed at 264 hPH. When metamorphosis was complete at 768 hPH, the larvae became juveniles. The current study presents the first results about early development of B. splendens and provides relevant information for its reproduction, rearing and biology. PMID- 24229612 TI - A rally for traumatic brain injury research. PMID- 24229613 TI - INMiND: getting to the bottom of neuroinflammation. PMID- 24229615 TI - Electrographic seizures and status epilepticus in critically ill children and neonates with encephalopathy. AB - Electrographic seizures are seizures that are evident on EEG monitoring. They are common in critically ill children and neonates with acute encephalopathy. Most electrographic seizures have no associated clinical changes, and continuous EEG monitoring is necessary for identification. The effect of electrographic seizures on outcome is the focus of active investigation. Studies have shown that a high burden of electrographic seizures is associated with worsened clinical outcome after adjustment for cause and severity of brain injury, suggesting that a high burden of such seizures might independently contribute to secondary brain injury. Further research is needed to determine whether identification and management of electrographic seizures reduces secondary brain injury and improves outcome in critically ill children and neonates. PMID- 24229616 TI - Axonal Guillain-Barre syndrome: concepts and controversies. AB - Acute motor axonal neuropathy (AMAN) is a pure motor axonal subtype of Guillain Barre syndrome (GBS) that was identified in the late 1990s. In Asia and Central and South America, it is the major subtype of GBS, seen in 30-65% of patients. AMAN progresses more rapidly and has an earlier peak than demyelinating GBS; tendon reflexes are relatively preserved or even exaggerated, and autonomic dysfunction is rare. One of the main causes is molecular mimicry of human gangliosides by Campylobacter jejuni lipo-oligosaccharides. In addition to axonal degeneration, electrophysiology shows rapidly reversible nerve conduction blockade or slowing, presumably due to pathological changes at the nodes or paranodes. Autoantibodies that bind to GM1 or GD1a gangliosides at the nodes of Ranvier activate complement and disrupt sodium-channel clusters and axoglial junctions, which leads to nerve conduction failure and muscle weakness. Improved understanding of the disease mechanism and pathophysiology might lead to new treatment options and improve the outlook for patients with AMAN. PMID- 24229617 TI - Long-term effects of cariprazine exposure on dopamine receptor subtypes. AB - INTRODUCTION: All clinically effective antipsychotics are known to act on the dopaminergic system, and previous studies have demonstrated that repeated treatment with antipsychotics produced region-specific changes in dopamine receptor levels. Cariprazine is a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. We examined the effects of chronic cariprazine administration on dopamine receptor levels. METHODS: Rats were administered either vehicle or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Dopamine receptor levels were quantitated using autoradiographic assays on brain tissue sections from the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), caudate putamen (CPu), hippocampus (HIPP), olfactory tubercle (OT), and islands of Calleja (ICj). RESULTS: Chronic treatment with cariprazine did not alter D1 receptor levels in any brain region tested. Cariprazine increased D2 receptor levels in mPFC (27%-43%), NAc (40%-45%), medial (41%-53%) and lateral (52%-63%) CPu, and HIPP (38%). Cariprazine dose-dependently upregulated D3 receptor levels in ICj (32%-57%), OT (27%-67%), and NAc shell (31%-48%). Repeated cariprazine treatment increased D4 receptor in NAc (53%-82%), medial (54%-98%) and lateral (58%-74%) CPu, and HIPP (38%-98%). CONCLUSION: Similar to other antipsychotics, cariprazine upregulated D2 and D4 receptor levels in various brain regions. Cariprazine was unique among antipsychotics in increasing D3 receptor levels, which may support its unique psychopharmacologic properties. PMID- 24229618 TI - Influenza in hospitalized children in Ireland in the pandemic period and the 2010/2011 season: risk factors for paediatric intensive-care-unit admission. AB - Influenza causes significant morbidity and mortality in children. This study's objectives were to describe influenza A(H1N1)pdm09 during the pandemic, to compare it with circulating influenza in 2010/2011, and to identify risk factors for severe influenza defined as requiring admission to a paediatric intensive care unit (PICU). Children hospitalized with influenza during the pandemic were older, and more likely to have received antiviral therapy than children hospitalized during the 2010/2011 season. In 2010/2011, only one child admitted to a PICU with underlying medical conditions had been vaccinated. The risk of severe illness in the pandemic was higher in females and those with underlying conditions. In 2010/2011, infection with influenza A(H1N1)pdm09 compared to other influenza viruses was a significant risk factor for severe disease. An incremental relationship was found between the number of underlying conditions and PICU admission. These findings highlight the importance of improving low vaccination uptake and increasing the use of antivirals in vulnerable children. PMID- 24229619 TI - Oral squamous cell carcinoma and serum paraoxonase 1. AB - BACKGROUND: Serum paraoxonase 1 is involved in mechanisms that protect cells from oxidative stress damage. This study aimed to investigate the correlation between serum paraoxonase 1 activity and polymorphisms in patients with oral squamous cell carcinoma. METHODS AND MATERIALS: Fifty-seven patients with oral squamous cell carcinoma and 59 matched healthy controls participated in the study. Serum paraoxonase 1 activity and polymorphisms in blood samples were compared with results for polymerase chain reaction and restriction fragment length polymorphism tests. RESULTS: Mean serum paraoxonase 1 activity levels were lower in patients than controls (mean +/- standard deviation, 21.9 +/- 5 units/l and 120.4 +/- 2 units/l, respectively) (p = 0.001). The serum paraoxonase 1 192 glutamine polymorphism was more common in patients than controls. CONCLUSION: Patients with oral squamous cell carcinoma had significantly lower serum paraoxonase 1 activity levels and a greater prevalence of the serum paraoxonase 1 192 glutamine allele, compared with controls. Serum paraoxonase 1 may play a role in the aetiology of oral squamous cell carcinoma. PMID- 24229620 TI - Long-chain n-3 DHA reduces the extent of skeletal muscle fatigue in the rat in vivo hindlimb model. AB - Dietary fish oil modifies skeletal muscle membrane fatty acid composition and oxygen efficiency similar to changes in the myocardium. Oxygen efficiency is a key determinant of sustained force in mammalian skeletal muscle. Therefore, in the present study, we tested the effects of a fish-oil diet on skeletal muscle fatigue under the stress of contraction using the rat in vivo autologous perfused hindlimb model. For 8 weeks, male Wistar rats were fed a diet rich in saturated fat (SF), a diet rich in n-6 PUFA or a diet rich in long-chain (LC) n-3 PUFA DHA derived from fish oil. In anaesthetised, mechanically ventilated rats, with their hindlimbs perfused with arterial blood at a constant flow, the gastrocnemius plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12 V, 0.05 ms) to contract repetitively for 30 min. Rats fed the n-3 PUFA diet developed higher maximum twitch tension than those fed the SF and n-6 PUFA diets (P< 0.05) and sustained twitch tension through more repetitions before the tension declined to 50 % of the maximum twitch tension (P< 0.05). The n-3 PUFA group used less oxygen for tension developed and produced higher venous lactate concentrations with no difference in glycogen utilisation compared with the SF and n-6 PUFA groups. These results further support that incorporation of DHA into skeletal muscle membranes increases the efficiency of oxygen use over a range of contractile force and this is expressed as a higher sustained force and prolonged time to fatigue. PMID- 24229621 TI - [Effects of artesunate on the invasion of lung adenocarcinoma A549 cells and expression of ICAM-1 and MMP-9]. AB - BACKGROUND AND OBJECTIVE: Artesunate, an anti-malarial drug, elicits an inhibitory effect on pulmonary carcinoma. However, the mechanisms of artesunate activity on pulmonary carcinoma have not been completely elucidated. The aim of this study is to investigate the effect of artesunate on the invasion of human lung adenocarcinoma A549 cells. METHODS: The inhibitory effect of artesunate on the proliferation and invasion of A549 cells was determined in vitro by MTT assay and transwell chamber invasion assay, respectively. A nude mouse model of human lung A549 cell xenograft tumor was established. The inhibitory effect of artesunate on the tumor of the mouse model as well as ICAM-1 and MMP-9 protein expressions were determined by Western blot. RESULTS: A low dose of artesunate ranging between 1.25 MUg/L and 5 MUg/L did not significantly inhibit the proliferation of A549 cells in vitro. By contrast, 1.25 MUg/L artesunate inhibited the invasion of A549 cells in vitro as determined by transwell chamber invasion assay (96.33 +/- 6.41 vs 75.43 +/- 4.37, P<0.05). Although 10 mg/kg artesunate did not significantly inhibit A549 xenograft tumor proliferation (P>0.05), artesunate decreased the ICAM-1 and MMP-9 protein levels in the mouse model (P<0.05). CONCLUSIONS: Artesunate could inhibit the invasion of human lung adenocarcinoma A549 cells by possibly downregulating ICAM-1 and MMP-9 expressions. PMID- 24229622 TI - [Second-line chemotherapy and its survival analysis of 181 patients with extensive-stage small cell lung cancer in a single institute]. AB - BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. METHODS: 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. chi(2) test was used to analysis the differences of enumeration data and between different groups. Kaplan Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. RESULTS: The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P<0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. The median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). The response rate among six regimens was significantly different (P=0.017); There was not statistical significance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. The differences of OS and PFS between six regimens in second-line therapy were not statistically different (P=0.914, P=0.293). CONCLUSIONS: The most significant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. The most optimal second-line chemotherapy regimen with definite curatice effect was controversial. PMID- 24229623 TI - The value of CT attenuation in distinguishing atypical adenomatous hyperplasia from adenocarcinoma in situ. AB - BACKGROUND AND OBJECTIVE: Advances in high-resolution computed tomography (CT) scanning have increased the detection of small ground-glass opacity (GGO) nodules and also allowed such images to be investigated in detail. However, it is difficult to differentiate atypical adenomatous hyperplasia (AAH) from adenocarcinoma in situ (AIS) with CT, even at follow-up, because they share many similar CT manifestations. While AAH is thought to be a precursor or even an early-stage lesion of lung adenocarcinoma, and the stepwise progression from AAH to AIS is thought to be reasonable. Therefore, the hypothesis that the attenuation of GGO is increased gradually from AAH to AIS is proposed. The aim of this study was to distinguish AAH from AIS with CT attenuation in patients with pure GGO nodules. METHODS: Between January 2010 and December 2012, the CT findings in terms of the greatest diameter and mean CT attenuation (HU) were reviewed and correlated with pathology in 56 patients with AAH (n=21) and non mucinous AIS (n=38) by two independent observers. All the 59 lesions were pure GGO nodules with size of 2 cm or smaller. To determine variability of measuring CT attenuation, we calculated the 95% confidence interval (CI) for the limits of agreement by using Bland-Altman analysis. Student t test was used to compare AAH and AIS in terms of diameter and CT attenuation. And receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of mean CT attenuation for differentiating AAH from AIS and obtain the diagnostic value. Two-tailed P value of less than 0.05 was considered to be significant. RESULTS: For the manually measured CT attenuation, the 95%CI for the limits of agreement was -40 HU, 50 HU for inter-observer variability. Although there was significant difference in nodule diameter between AAH and AIS (P=0.046), the overlap was considerable. The mean CT attenuation was (-718 +/- 53) HU (95%CI: 822, -604) for AAH, which was significantly smaller than (-600 +/- 35) HU (95%CI: -669, -531) for AIS (P=0.013). The area under curve (AUC) from ROC was 0.903 for differentiating AAH from AIS, and the cut-off value of -632 HU was optimal for differentiation between AAH and AIS, with sensitivity of 0.79, specificity of 0.95, and accuracy of 0.85. CONCLUSIONS: The mean CT attenuation can help the radiological differentiation between AAH and AIS. PMID- 24229624 TI - [Research for mediastinal lymph node desection style of stage Ib upper lobe non small cell lung cancer]. AB - BACKGROUND AND OBJECTIVE: Lymphatic metastasis is the most important way for the spread of lung cancer and is one of the important factors affecting the prognosis. Existing studies showed that compared to middle or lower lobe NSCLC, upper lobe non-small cell lung cancer (NSCLC) has a higher probability of occurring regional mediastinal lymph node metastasis. The purpose of this study is to research the prognostic factors and lymphadenectomy of stage Ib upper lobe NSCLC. METHODS: A retrospective study of 147 consecutive subjects (76 and 71 for right and left upper lobe NSCLC respectively) who had undergone curative resection for stage Ib upper lobe NSCLC was performed. A total of 925 lymph nodes were removed during the surgery in all enrolled patients and a total of 491 mediastinal lymph nodes (266 and 225 for superior and inferior mediastinal lymph nodes respectively) were removed. Kaplan-Meier product method and Log-rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. RESULTS: 1Both univariate and multivariate analysis showed that age, tumor size and number of removed superior mediastinal lymph node stations were the important prognostic factors of stage Ib upper lobe NSCLC; 2For stage Ib right upper lobe NSCLC, station 4 lymph node was of statistical significance to the prognosis (P=0.021); while for stage Ib left upper lobe NSCLC, station 5 lymph node was of statistical significance to the prognosis (P=0.024). CONCLUSIONS: In surgically treated stage Ib upper lobe NSCLC patients, age, tumor size and number of removed superior mediastinal lymph node stations are the important prognostic factors. And in this kind of patients, lobe specific systematic lymph node dissection may be a more efficient procedure during the surgery. PMID- 24229625 TI - [The expression and significance of stem cell transcription factor Sox2 in lung carcinoma]. AB - BACKGROUND AND OBJECTIVE: Transcription factor Sox2 remains the pluripotency of stem cell, participates in self-renew of cancer stem cell and plays important role during the initiation and development of various cancers. This study intends to investigate the expression and significance of Sox2 and Sox2 autoantibodies (Sox2-Ab) in tissue and serum of patients with non-small cell lung cancer (NSCLC). METHODS: Expression of Sox2 gene and protein was tested in 58 cases of NSCLC, 16 patients with other tumors and 20 cases of normal lung tissue specimens by quantitative PCR and immunohistochemical assay, respectively. Serum Sox2-Ab level was detected in 30 cases of NSCLC patients and 30 healthy controls by ELISA method. Clinical and pathological data from patients were collected and analyzed retrospectively. RESULTS: Expression levels of Sox2 mRNA and protein were higher in patient with NSCLC than other groups, with statistically significant differences (P<0.01), respectively. Meanwhile, Sox2 mRNA expression increased in NSCLC patients associated with histological type and tumor size. No significant differences in Sox2-Ab serum levels were found between NSCLC patients and normal subjects. CONCLUSIONS: Sox2 in NSCLC have a higher expression, which is closely related to histological type and tumor size. Sox2 might use as a potential biomarker and therapeutic target for lung cancer. PMID- 24229626 TI - [Postoperative survival of patients with stage IIIa non-small cell lung cancer]. AB - BACKGROUND AND OBJECTIVE: At present, surgery is advocated for stage IIIa non small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients. METHODS: Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant. RESULTS: 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P<0.05). The maximum diameter of tumor had a significant influence on PFS only in univariate analysis. CONCLUSIONS: For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no benefit on them. PMID- 24229627 TI - [Summary of "Expert consensus for treatment of bone metastases in lung cancer" reviewers meeting]. PMID- 24229628 TI - [The function and molecular mechnism of cyclin Y protein]. AB - A novel cyclin, cyclin Y, is one of the most highly conserved members of the cyclin superfamily, which is famous for their important roles in regulating the cell cycle and transcription. Recently, it was found that cyclin Y was up regulated in many cancers. Cyclin Y may play a crucial role in tumor progression. The function and molecular mechanism of cyclin Y protein will be discussed in this paper. PMID- 24229629 TI - [Advanced research of fibroblast growth factor receptor in non-small cell lung cancer]. AB - Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR) gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF) pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR) in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer. PMID- 24229630 TI - [Significances of RET fusion gene in non-small cell lung cancer]. AB - Lung cancer is the leading cause of cancer-related death worldwide, molecular target therapy has become a hot research direction of non-small cell lung cancer (NSCLC) treatment. RET fusion gene with an identifiable clinical pathological features, is present in some subsets of lung cancer, and its treatment is effective by RET inhibitor, suggesting that RET fusion gene may be a new target for individualized treatment to the subgroup of NSCLC. This article reviews the structural characteristics of RET fusion gene and expression model in clinical samples, and treatment of NSCLC. PMID- 24229631 TI - The evolving view of rosacea. PMID- 24229632 TI - New insights into rosacea pathophysiology: a review of recent findings. AB - Rosacea is a common, chronic inflammatory skin disease of poorly understood origin. Based on its clinical features (flushing, chronic inflammation, fibrosis) and trigger factors, a complex pathobiology involving different regulatory systems can be anticipated. Although a wealth of research has shed new light over recent years on its pathophysiology, the precise interplay of the various dysregulated systems (immune, vascular, nervous) is still poorly understood. Most authors agree on 4 major clinical subtypes of rosacea: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. Still, it needs to be elucidated whether these subtypes develop in a consecutive serial fashion or if any subtypes may occur individually as part of a syndrome. Because rosacea often affects multiple family members, a genetic component is also suspected, but the genetic basis of rosacea remains unclear. During disease manifestation and early stage, the innate immune system and neurovascular dysregulation seem to be driving forces in rosacea pathophysiology. Dissection of major players for disease progression and in advanced stages is severely hampered by the complex activation of the innate and adaptive immune systems, enhanced neuroimmune communication, profound blood vessel and possibly lymphatic vessel changes, and activation of almost every resident cell in the skin. This review discusses some of the recent findings and aims to build unifying hypotheses for a modern understanding of rosacea pathophysiology. PMID- 24229633 TI - Medical history of the representation of rosacea in the 19th century. AB - Throughout the 1800s, clinical illustrations helped to formalize what was then the recently developed field of dermatology. Knowledge of skin diseases was given new dimension as artists and clinicians alike strove to accurately document the physical characteristics of numerous dermatoses. Introduction of novel processes and refined techniques advanced the clinical use of disease images. The increasingly superior quality of these images aided in the early distinction between rosacea and acne. This article highlights these illustrative contributions in dermatology, and includes key images that serve as a road map to early clinical understanding of skin diseases. PMID- 24229634 TI - Rosacea: current state of epidemiology. AB - Case definitions are critical in epidemiologic research. However, modern disease indicators must now consider complex data from gene-based research along with traditional clinical parameters. Rosacea is a skin disorder with multiple signs and symptoms. In individuals, these features may be multiple or one may predominate. While studies on the epidemiology of rosacea have previously been sparse, there has been a recent increase in research activity. A broader body of epidemiological information that includes a greater variety of countries beyond Northern Europe and general population-based demographics is needed. As there are operational issues in current case definitions of rosacea subtypes- rationalization and standardization--universal consistent applications in future research is also imperative. Further improvement in disease definition combining new research information along with clinical pragmatism should increase the accuracy of rosacea case ascertainment and facilitate further epidemiological research. PMID- 24229635 TI - Ocular rosacea: common and commonly missed. AB - Rosacea is a prevalent disorder that may be disfiguring and cause significant ocular morbidity, if not diagnosed and managed appropriately. Ocular rosacea, in particular, is often left undiagnosed as no specific test is available to confirm the diagnosis. Accurate diagnosis is further complicated because symptoms of ocular rosacea are not always specific to the disorder alone. Other ophthalmic disorders may present with similar findings. Further challenges exist because the severity of ocular symptoms is often not related to the severity of cutaneous findings in rosacea. Isolating a disease marker may facilitate earlier diagnosis and treatment, and could also contribute to better understanding of disease pathogenesis. The glycomics of tear fluid and saliva in patients with rosacea shows promise as an initial step in the search for a biomarker specific to the disease. We have previously found potentially important disease biomarkers in roseatic tear and saliva samples. Further investigation should prove important in the early stages of developing a set of markers for accurate disease identification. PMID- 24229636 TI - Ocular rosacea: a dermatologic perspective. AB - As many as 50% of patients given the diagnosis of cutaneous rosacea also have ocular rosacea. Conservative figures indicate that approximately 10 million patients are affected by ocular rosacea in the United States alone. Despite this prevalence, ocular symptoms of rosacea are often improperly diagnosed, particularly when they occur in the absence of skin involvement. PMID- 24229637 TI - Management of facial erythema of rosacea: what is the role of topical alpha adrenergic receptor agonist therapy? AB - Several more recent advances have led to a better understanding of the pathophysiologic mechanisms involved in rosacea and therapeutic modalities used for treatment. Although the clinical features may vary among patients, there are some unifying mechanisms that appear to relate to the more common presentations of rosacea. Both neurovascular dysregulation and augmented immune detection and response appear to play central roles that lead to many of the signs and symptoms of rosacea. Diffuse central facial erythema is a very common finding that intensifies during flares and persists to varying degrees between flares. This background of facial redness occurs secondary to vasodilation and fixed vascular changes that develop over time. Physical modalities are commonly used to treat the erythema that persists as a result of fixed changes in superficial cutaneous vasculature that do not remit after treatment with agents whose mechanisms are active primarily against some of the inflammatory processes operative in rosacea (ie metronidazole, azelaic acid, tetracyclines). As enlarged superficial cutaneous vessels that contribute to the fixed background facial redness of rosacea remain vasoactive to sympathetic nervous system innervation, topical alpha-adrenergic receptor agonists, namely brimonidine and oxymetazoline, are currently under evaluation for the treatment of facial erythema of rosacea. This article focuses on the clinical differentiation of facial erythema of rosacea and its management. PMID- 24229638 TI - Emerging therapies in rosacea. AB - Rosacea is a common skin disorder with multiple symptoms. The emergence of research that furthers understanding of pathophysiological mechanisms has created new targets for disease treatment. Specifically, there is a need for new treatments that address the various erythematic symptoms associated with rosacea. Systemic and topical therapies have both yielded positive results in treating rosacea with various medications. Subantimicrobial-dose doxycycline is one such promising treatment. Development of novel products in the near future should help achieve more satisfactory outcomes for patients. PMID- 24229640 TI - Tugging organs into place. AB - In this issue of Developmental Cell, Weavers and Skaer (2013) show that interplay between two opposing forces generated by tip cell attachment to muscles and migration of kink cells allows for the formation of the looped shape and positioning of renal tubules within the body of a fly larva. PMID- 24229639 TI - Test-retest reliability and sensitivity to change of the dimensional anxiety scales for DSM-5. AB - OBJECTIVE: This article reports on the test-retest reliability and sensitivity to change of a set of brief dimensional self-rating questionnaires for social anxiety disorder (SAD-D), specific phobia (SP-D), agoraphobia (AG-D), panic disorder (PD-D), and generalized anxiety disorder (GAD-D), as well as a general cross-cutting anxiety scale (Cross-D), which were developed to supplement categorical diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). METHODS: The German versions of the dimensional anxiety scales were administered to 218 students followed up approximately 2 weeks later (Study 1) and 55 outpatients (23 with anxiety diagnoses) followed-up 1 year later (Study 2). Probable diagnostic status in students was determined by the DIA-X/M-CIDI stem screening-questionnaire (SSQ). In the clinical sample, Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses were assessed at Time 1 using the DIA-X/M-CIDI. At Time 2, the patient version of the Clinical Global Impression-Improvement scale (CGI-I) was applied to assess change. RESULTS: Good psychometric properties, including high test retest reliability, were found for the dimensional scales except for SP-D. In outpatients, improvement at Time 2 was associated with significant decrease in PD D, GAD-D, and Cross-D scores. Discussion Major advantages of the scales include that they are brief, concise, and based on a consistent template to measure the cognitive, physiological, and behavioral symptoms of fear and anxiety. Further replication in larger samples is needed. Given its modest psychometric properties, SP-D needs refinement. CONCLUSION: Increasing evidence from diverse samples suggests clinical utility of the dimensional anxiety scales. PMID- 24229641 TI - Disinherited daughters travel by tube. AB - Reporting in Developmental Cell, Packard et al. (2013) identify a peculiar mitotic behavior in ureteric bud tips whereby dividing cells leave the epithelium for the lumen, retaining only a slender connection with basement membrane. One daughter inherits its mother's location, whereas the other moves along the lumen and reintegrates there. PMID- 24229642 TI - Response: the "tail" of the twin adaptors. PMID- 24229643 TI - The Purkinje neuron acts as a central regulator of spatially and functionally distinct cerebellar precursors. AB - The prospective white matter (PWM) in the nascent cerebellum contains a transient germinal compartment that produces all postnatally born GABAergic inhibitory interneurons and astrocytes. However, little is known about the molecular identity and developmental potential of resident progenitors or key regulatory niche signals. Here, we show that neural stem-cell-like primary progenitors (Tnc(YFP-low) CD133(+)) generate intermediate astrocyte (Tnc(YFP-low) CD15(+)) precursors and GABAergic transient amplifying (Ptf1a(+)) cells. Interestingly, these lineally related but functionally divergent progenitors commonly respond to Sonic hedgehog (Shh), and blockade of reception in TNC(YFP-low) cells attenuates proliferation in the PWM, reducing both intermediate progenitor classes. Furthermore, we show that Shh produced from distant Purkinje neurons maintains the PWM niche independently of its classical role in regulating granule cell precursor proliferation. Our results indicate that Purkinje neurons maintain a bidirectional signaling axis, driving the production of spatially and functionally opposed inhibitory and excitatory interneurons important for motor learning and cognition. PMID- 24229644 TI - A common set of DNA regulatory elements shapes Drosophila appendages. AB - Animals have body parts made of similar cell types located at different axial positions, such as limbs. The identity and distinct morphology of each structure is often specified by the activity of different "master regulator" transcription factors. Although similarities in gene expression have been observed between body parts made of similar cell types, how regulatory information in the genome is differentially utilized to create morphologically diverse structures in development is not known. Here, we use genome-wide open chromatin profiling to show that among the Drosophila appendages, the same DNA regulatory modules are accessible throughout the genome at a given stage of development, except at the loci encoding the master regulators themselves. In addition, open chromatin profiles change over developmental time, and these changes are coordinated between different appendages. We propose that master regulators create morphologically distinct structures by differentially influencing the function of the same set of DNA regulatory modules. PMID- 24229645 TI - Tip cells act as dynamic cellular anchors in the morphogenesis of looped renal tubules in Drosophila. AB - Tissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative to one another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergent extension movements lengthen the tubule. Tip cell anchorage antagonizes forward directed, TGF-beta-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function. PMID- 24229646 TI - Cytoplasmic streaming velocity as a plant size determinant. AB - Cytoplasmic streaming is active transport widely occurring in plant cells ranging from algae to angiosperms. Although it has been revealed that cytoplasmic streaming is generated by organelle-associated myosin XI moving along actin bundles, the fundamental function in plants remains unclear. We generated high- and low-speed chimeric myosin XI by replacing the motor domains of Arabidopsis thaliana myosin XI-2 with those of Chara corallina myosin XI and Homo sapiens myosin Vb, respectively. Surprisingly, the plant sizes of the transgenic Arabidopsis expressing high- and low-speed chimeric myosin XI-2 were larger and smaller, respectively, than that of the wild-type plant. This size change correlated with acceleration and deceleration, respectively, of cytoplasmic streaming. Our results strongly suggest that cytoplasmic streaming is a key determinant of plant size. Furthermore, because cytoplasmic streaming is a common system for intracellular transport in plants, our system could have applications in artificial size control in plants. PMID- 24229648 TI - Comparative expression analysis of embryonic development-related genes at different stages of parthenogenetic and in vitro fertilized embryos in caprine. AB - Aberrant gene expression occurs in parthenogenetic embryos due to abnormal epigenetic modifications in the genome that probably diminish viability and enhance developmental abnormalities in these embryos. In the present study, five developmentally important genes (HPRT1, Cx43, Sox2, Mest and IGF2R) were analysed at different stages in parthenotes (haploid and diploid) and compared with similar stages in in vitro fertilized (IVF) embryos. The results indicated that in haploid parthenotes expression of HPRT1 was upregulated (P < 0.05) only at the 2-4-cell stage whereas Cx43 expression was significantly (P < 0.05) downregulated in all stages as compared with the control. However, expression of this gene was upregulated (P < 0.05) in 2-4-cell and morula stages of diploid parthenotes. Expression of Sox2 was significantly (P < 0.05) downregulated in morula stage haploid parthenotes, whereas it was upregulated (P < 0.05) in 8-16-cell stage diploid embryos. The expression of Mest was upregulated (P < 0.05) at the 2-4 cell stage of both haploid and diploid parthenotes, whereas it was downregulated in 8-16-cell stage diploid embryos as compared with control. IGF2R expression was upregulated (P < 0.05) only in morula stage haploid and diploid parthenote as compared with control. These results indicate that parthenogenetic embryos showed aberrant gene expression of developmentally important genes such as HPRT1, Cx43, Sox2, Mest and IGF2R in comparison with IVF embryos, this finding may be one of the major reasons for the poor developmental competence of parthenogenetic embryos. PMID- 24229647 TI - The adaptor protein-1 MU1B subunit expands the repertoire of basolateral sorting signal recognition in epithelial cells. AB - An outstanding question in protein sorting is why polarized epithelial cells express two isoforms of the MU1 subunit of the AP-1 clathrin adaptor complex: the ubiquitous MU1A and the epithelial-specific MU1B. Previous studies led to the notion that MU1A and MU1B mediate basolateral sorting predominantly from the trans-Golgi network (TGN) and recycling endosomes, respectively. Using improved analytical tools, however, we find that MU1A and MU1B largely colocalize with each other. They also colocalize to similar extents with TGN and recycling endosome markers, as well as with basolateral cargoes transiting biosynthetic and endocytic-recycling routes. Instead, the two isoforms differ in their signal recognition specificity. In particular, MU1B preferentially binds a subset of signals from cargoes that are sorted basolaterally in a MU1B-dependent manner. We conclude that expression of distinct MU1 isoforms in epithelial cells expands the repertoire of signals recognized by AP-1 for sorting of a broader range of cargoes to the basolateral surface. PMID- 24229649 TI - Parameter identifiability and Extended Multiple Studies Analysis of a compartmental model for human vitamin A kinetics: fixing fractional transfer coefficients for the initial steps in the absorptive process. AB - In the existing compartmental models of human vitamin A metabolism, parameters related to the absorption of the isotopic oral dose have not been well identified. We hypothesised that fixing some poorly identified parameters related to vitamin A absorption would improve parameter identifiability and add statistical certainty to such models. In the present study, data for serum vitamin A kinetics in nine subjects given [2H8]retinyl acetate orally and a model with absorption fixed at 75 % were used to test this hypothesis. In addition to absorption efficiency, we fixed two other fractional transfer coefficients: one representing the initial processing of the ingested dose and the other representing the direct secretion of retinol bound to retinol-binding protein (RBP) from enterocytes into the plasma. The Windows version of Simulation, Analysis and Modeling software (WinSAAM) was used to fit serum tracer data v. time for each subject. Then, a population model was generated by WinSAAM's Extended Multiple Studies Analysis. All the parameters had fractional standard deviations < 0.5, and none of the pairs of parameters had a correlation coefficient >0.8 (accepted criteria for well-identified parameters). Similar to the values predicted by the original model, total traced mass for retinol was 1160 (sd 468) MUmol, and the time for retinol to appear in the plasma bound to RBP was 31.3 (sd 4.4) h. In conclusion, we suggest that this approach holds promise for advancing compartmental modelling of vitamin A kinetics in humans when the dose must be administered orally. PMID- 24229650 TI - Nutritional influences on age-related skeletal muscle loss. AB - Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1-Akt-FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid-base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required. PMID- 24229651 TI - Late life depression: a global problem with few resources. AB - Mental health disorders in terms of an aging population are discussed in this review. Statistics on depression in later life are presented with a discussion of physical health comorbidities. This presentation postulates that the health care infrastructure currently in place is inadequate to meet the present, much less the future, needs of this population. The care of the depressed elder will require the coordinated effort of psychiatrists, psychologists, social workers, nurse practitioners and advanced practice psychiatric nurses, internal medicine gerontologists, internal medicine and family medicine general physicians, community agencies, and volunteers. PMID- 24229652 TI - What characterizes late-life depression? AB - This article analyzes late-life depression, looking carefully at what defines a person as elderly, the incidence of late-life depression, complications and differences in symptoms between young and old patients with depression, subsyndromal depression, bipolar depression in the elderly, the relationship between grief and depression, along with sleep disturbances and suicidal ideation. PMID- 24229655 TI - The two-way relationship between medical illness and late-life depression. AB - This article reviews some common medical conditions and the interaction between those illnesses and depression in the geriatric population. The authors aim to help clarify the 2-way interaction between depression and these medical conditions, especially in older individuals, and impart some important diagnostic and treatment considerations to the practicing physician. The presence of multiple conditions further complicates treatment, as does associated medication use, substance abuse problems (often underappreciated in the elderly), age related changes in sleep architecture, and an array of other psychosocial and environmental factors that can contribute to the development of depression. PMID- 24229653 TI - What are the causes of late-life depression? AB - Although depression in old age is less common than depression in younger populations, it still affects more than 1 million community-living older adults. Depression in late life has been associated with reduced quality of life and increased mortality from both suicide and illness. Its causes are multifactorial but are prominently related to both biologic and social factors. Psychological factors, although less studied in elders, are also important in understanding its cause. In this article, multiple facets of late-life depression are reviewed, including its clinical presentation, epidemiology, and biopsychosocial causes. PMID- 24229656 TI - Assessment of the person with late-life depression. AB - This article discusses characteristic factors in the presentation of depressive disorders in persons older than age 65 years. Clinical presentation is discussed along with risk and protective factors. Detailed descriptions of tests useful for screening and diagnosis of depression in the elderly are presented. Each test is reviewed according to time to administer, sensitivity and specificity, outcomes, advantages, and disadvantages. The importance of clinical history and the diagnostic interview, as well as the role of laboratory studies and neuroimaging in the clinical evaluation are discussed. PMID- 24229654 TI - Cognitive deficits in geriatric depression: clinical correlates and implications for current and future treatment. AB - The purpose of this article is to identify the cognitive deficits commonly associated with geriatric depression and describe their clinical significance. The complex relationship between geriatric depression and dementia is summarized and possible shared mechanisms discussed. Evidence regarding whether the cognitive deficits in depression may be mitigated with medication or with computerized cognitive remediation is presented. PMID- 24229657 TI - Psychological treatment of late-life depression. AB - This article summarizes the following psychological interventions for late-life depression: cognitive and behavioral therapy, problem-solving therapy, reminiscence and life review therapy, brief psychodynamic therapy, and interpersonal therapy. Results indicate that all psychological interventions reviewed were effective in reducing depressive symptoms in older adults. Future research should include larger sample sizes and focus on moderators of treatment such as age, depression severity, medical illness, and cognitive impairment. PMID- 24229658 TI - What is the role of alternative treatments in late-life depression? AB - Late-life depression remains challenging to treat. One major limitation to treatment is the concern over medication-related side effects to which the elderly are especially vulnerable. Also, because many elderly people are already taking multiple medications for medical conditions, there is the concern over drug-drug interactions. This article reviews various complementary and alternative medicine interventions for late-life depression, including natural remedies, exercise, yoga, tai chi, massage therapy, music therapy, and religion and spirituality. PMID- 24229659 TI - What is the role of medications in late life depression? AB - In this article, the efficacy and side effects of antidepressants in the elderly are discussed. In addition, whether the elderly in general should be treated with lower doses of antidepressants, and whether the elderly have a slower response to antidepressant treatment, are also discussed. PMID- 24229660 TI - The role of electroconvulsive and neuromodulation therapies in the treatment of geriatric depression. AB - Geriatric depression is associated with increased mortality because of suicide and decreases in functional and physical health. Many elders' depression is resistant to psychotherapy and medication and can become chronic. Electroconvulsive therapy (ECT) is increasingly used in the treatment of medication-resistant or life-threatening geriatric depression. Neuromodulation therapies (subconvulsive, focal, or subconvulsive and focal) are alternatives for the management of treatment-resistant depression in the elderly. Therapies that combine both strategies could be safer but may not be as effective as ECT. This review covers the evidence on the safety and efficacy of ECT and the neuromodulation therapies in geriatric depression. PMID- 24229662 TI - A team-based approach to the care of depression in later life: where are we now? AB - This article reviews briefly the historical genesis of collaborative and team based models of care, including the results of projects that have been reported through the mid 2000s. A more comprehensive review of research and project outcomes published during the last 5 years on this model of care addressing either depression or depression with comorbid conditions follows. PMID- 24229663 TI - Late life depression. PMID- 24229661 TI - The economic, public health, and caregiver burden of late-life depression. AB - This article reviews the burden of late-life depression (LLD) from several perspectives, including costs of depression treatment and treatment of other comorbid psychiatric and medical conditions; the impact of LLD on job functioning, disability, and retirement; and how LLD influences others, such as family members and caregivers. PMID- 24229664 TI - Biologic therapies in type 1 diabetes: how far are they from us? PMID- 24229665 TI - Change of glutamic acid decarboxylase antibody and protein tyrosine phosphatase antibody in Chinese patients with acute-onset type 1 diabetes mellitus. AB - BACKGROUND: Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features. METHODS: Two hundreds and forty-seven Chinese newly diagnosed acute onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well. RESULTS: During the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of beta cell function. CONCLUSION: Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the beta cell function in Chinese patients. PMID- 24229666 TI - Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population. AB - BACKGROUND: The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies (GWAS) from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population. METHODS: Two single nucleotide polymorphisms (SNPs, rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay. The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis. A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals. RESULTS: rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P = 1.80*10(-7), OR (95% CI) = 1.22 (1.14-1.32), rs4402960 P = 7.46*10(-9), OR (95% CI) = 1.26 (1.17-1.37), respectively). Moreover, 11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579. The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95% CI = 1.10-1.19), P < 0.0001 under an additive model and rs4402960 OR of 1.14 (95% CI = 1.10-1.18), P < 0.0001 under an additive model). CONCLUSION: IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population. PMID- 24229667 TI - Correlation between blood glucose fluctuations and activation of oxidative stress in type 1 diabetic children during the acute metabolic disturbance period. AB - BACKGROUND: Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS). Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM). However, there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations. METHODS: We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011. They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS). Twenty-four hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2a (8-isoPGF2alpha). Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment. Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE), largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE). The correlations between glucose parameters and the index of oxidative stress were analyzed. RESULTS: Urine 8-isoPGF2alpha in the T1DM group was higher than that in the control group ((967.70+/-412.68) ng vs. (675.23+/-354.59) ng, P = 0.019). There was a correlation between urine 8 isoPGF2a level and MAGE (r = 0.321, P = 0.039), a significant correlation between low-density lipoprotein and urine 8-isoPGF2a level (r = 0.419, P = 0.03). There was no significant correlation between urine 8-isoPGF2alpha level and blood pressure, glycosylated hemoglobin (HbA1c), fasting C-peptide or other lipid indices. CONCLUSION: A correlation between urine 8-isoPGF2a levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM. PMID- 24229668 TI - Cross-sectional association of serum C-reactive protein and uric acid with albuminuria in Chinese type 2 diabetic patients. AB - BACKGROUND: Evidences show that subclinical chronic inflammation is involved in the pathogenesis of diabetic nephropathy. The aim of this study was to examine the relationship between serum C-reactive protein (CRP), serum uric acid, and albuminuria in Chinese type 2 diabetic patients. METHODS: A total of 1162 type 2 diabetic patients were recruited. All participants had relevant clinical and laboratory measurements. CRP was measured using a particle enhanced immunoturbidimetric assay. RESULTS: In the multiple linear regression model, natural log-transformed CRP (lnCRP) and uric acid were independent predictors of natural log-transformed urinary albumin to creatinine ratio (lnACR) (beta = 0.18, 95% CI 0.10-0.27, P < 0.001 and beta = 0.18, 95% CI 0.09-0.27, P < 0.001). The interaction of lnCRP with uric acid was also associated with lnACR (beta = 0.04, 95% CI 0.02-0.06, P < 0.001). In the full-adjusted logistic regression model, the OR for albuminuria of the patients in the third tertile levels of CRP and uric acid was 3.94 compared with patients in the first tertile levels of CRP and uric acid (95% CI 1.73-8.94, P < 0.001). CONCLUSIONS: Elevated serum CRP and increased serum uric acid level were associated with albuminuria in Chinese type 2 diabetic patients. Moreover, CRP and uric acid had an interactive effect on albuminuria. PMID- 24229669 TI - Basal insulin therapy strategy is superior to premixed insulin therapy in the perioperative period blood glucose management. AB - BACKGROUND: The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioperative period, insulin therapy is usually advised to be used for surgical patients with type 2 diabetes. However, the insulin regimen which one is better remains controversial. In this study, we estimated the efficacy, safety and advantage of different insulin therapy strategy during perioperative period. METHODS: A total of 1086 cases of surgical patients with type 2 diabetes mellitus enrolled in the present study. According to the glucose level at admission, all patients were divided into relatively high glucose group (group A, fasting blood glucose (FBG) <=13.9 mmol/L) and higher glucose group (group B, FBG >13.9 mmol/L). Patients in group A randomly accepted premixed insulin twice a day, or basal insulin plus oral medications, and were divided into group A1 and A2 respectively. Patients in group B randomly received premixed insulin twice daily, basal insulin plus oral hypoglycemic agents, or basal insulin plus preprandial insulin, and were divided into group B1, B2 and B3 respectively. The data of the preoperative preparation time, the daily doses of insulin used in different periods, postoperative incision healed installments, hypoglycemic events, the total hospitalization time, postoperative complications were all collected and statistically analyzed. RESULTS: Compared the main outcome measures in groups treated by premixed insulin therapy, both in preoperative preparation and postoperative period, the daily insulin dosage and the frequency of hypoglycemic events were decreased in groups treated by basal insulin therapy (P < 0.05). The preoperative preparation time and the total hospitalization time in groups with basal insulin therapy were shorter than that in groups with premixed insulin therapy (P < 0.05). The incision healing rate of stage I, II and III among different therapy protocols were significantly different (P < 0.05). CONCLUSIONS: Basal insulin therapy could be used in diabetic patients undergoing elective major and medium surgery during whole perioperative period. Basal insulin therapy strategy, including a single injection of basal insulin and basal insulin plus preprandial insulin injection subcutaneously, is superior to premixed insulin therapy in the perioperative blood glucose management, and it could be viewed as the best choice in glucose control during perioperative period. PMID- 24229670 TI - Effects of glucose and insulin on the H9c2 (2-1) cell proliferation may be mediated through regulating glucose transporter 4 expression. AB - BACKGROUND: The change of glucose transporter 4 (GLUT4) expression could influence glucose uptake in the myocardial cells and then effect myocardial metabolism, which maybe one of the factor for the diabetes cardiovascular disease. This study aimed to explore the influence of glucose and insulin at different concentrations on H9c2 (2-1) cell proliferation and its GLUT4 expression in vitro, and evaluate the correlation between myocardial cells proliferation and GLUT4 expression. This might be helpful for understanding the relationship between glucose metabolism and cardiovascular disease. METHODS: According to glucose concentrations in culture medium, cultured H9c2 rat myocardial cells were divided into five groups: control group (NC, glucose concentration 5.0 mmol/L), low glucose group (LG, glucose concentration 0.1 mmol/L), high glucose group 1 (HG1, glucose concentration 10 mmol/L), high glucose group 2 (HG2, glucose concentration 15 mmol/L), high glucose group 3 (HG3, glucose concentration 20 mmol/L). Then according to different insulin concentrations in culture medium, each group was further divided into two subgroups: normal insulin subgroup (INSc, insulin concentration 3.8 mU/L), high insulin subgroup (INSh, insulin concentration 7.6 mU/L). H9c2 (2-1) cells were cultured for 1, 2, 3 days, the proliferation of cells were assayed by cell counting Kit-8 assay, the expressions of GLUT4 mRNA and protein were detected with RT-PCR and Western Blotting technique, and the relation between myocardial cells proliferation and GLUT4 expression was evaluated. RESULTS: Compared with NC group, cell proliferation (OD value) was lower in LG, HG2, HG3 group but higher in HG1 group on the second and the third day (P < 0.05). There was a negative correlation between OD value and the glucose level in HG1, HG2, HG3 groups (P < 0.05). OD value in INSc subgroups was lower than that in INSh subgroups (P < 0.05). GLUT4 mRNA was lower in LG, HG2, HG3 groups than that in NC group (P < 0.05). Compared with NC group, GLUT4 mRNA level in HG1 group was higher on the first day but lower on the second and third day (P < 0.05). In HG1, HG2 and HG3 groups, GLUT4 mRNA level had a negative correlation with the level of glucose (P < 0.05). GLUT4 mRNA in INSc subgroups was lower than that in INSh subgroups (P < 0.05). The expression of GLUT4 protein was similar to that of GLUT4 mRNA. There was a positive correlation between H9c2 cell proliferation and GLUT4 expression (P < 0.02). CONCLUSIONS: Glucose levels could regulate glucose uptake in myocardial cells through influencing GLUT4 expression, and thus affected the cell proliferation and cell function. Insulin levels could affect the myocardial cell function by regulating GLUT4 expression. Effects of glucose and insulin on the myocardial cells proliferation might be mediated through regulating GLUT4 expression. There may be a mechanism of hyperglycemia pre-accommodation (HGPA) in myocardial cells mediated through regulation of GLUT4 expression. PMID- 24229671 TI - Effect of depot medroxyprogesterone acetate on bone mineral density in adolescent women. AB - BACKGROUND: Depot medroxyprogesterone acetate (DMPA) as a hormonal contraceptive is highly effective and widely used, but it may reduce bone mineral density (BMD) and increase the risk of osteoporosis. We compared BMD between users of intramuscular DMPA and nonhormonal subjects. METHODS: The study included 102 women aged between 16 and 18 years using DMPA for 24 months and 97 women aged between 16 and 18 years using nonhormonal contraception as nonusers control group. BMD of the lumbar spine and femoral neck was measured every 12 months for 24 months using dual-energy X-ray absorptiometry, comparing mean BMD changes in DMPA users and nonusers. RESULTS: There were no significant differences between groups at baseline in age, gynecologic age, body mass index (BMI), lumbar spine BMD and femoral neck BMD, etc. At 24 months of DMPA treatment, the mean percentage change from baseline in lumbar spine and femoral neck BMD values had decreased by 1.88% and 2.32%, respectively. The mean lumbar spine and femoral neck BMD in DMPA group at 24 months were not significantly different compared to baseline (P = 0.212 and P = 0.106, respectively). In comparison, in nonhormonal control group, there was a trend toward increasing BMD. At 24 months of observation, the mean percentage change from baseline in lumbar spine and femoral neck BMD had increased by 2.08% and 1.46%, respectively. There were no significant difference compared to baseline (P = 0.160 and P = 0.288, respectively). Mean BMD at the spine and femoral neck did not differ significantly between DMPA users and nonusers over 12-month, but the BMD values at both anatomical sites were significantly lower in DMPA users compared with nonusers after 24-month treatment (P = 0.009 and P = 0.009, respectively). CONCLUSION: The evidence of our study suggested that the use of DMPA for short term (<=12-month) has no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA may prevent the bone mass accrual in adolescents. PMID- 24229672 TI - Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway. AB - BACKGROUND: Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic beta-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic beta-cell apoptosis. METHODS: After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1, RINm5F (rat insulinoma cell line) cells were exposed to cytokines, interferon (IFN)-gamma alone, IFN gamma+interleukin (IL)-1beta, IFN-beta+IL-1beta+tumor necrosis factor (TNF)-alpha respectively. Pancreatic beta-cell apoptosis was assessed by using MTT, FACS, and caspase-3 activity assays. Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS), NF-kappaB and Fas were analyzed by RT-PCR. RESULTS: Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-gamma alone, IFN-gamma+IL-1beta and IFN gamma+TNF-alpha+IL-1beta mediated apoptosis. Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein. Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels. CONCLUSION: Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway. PMID- 24229673 TI - Pioglitazone inhibits the expression of nicotinamide adenine dinucleotide phosphate oxidase and p38 mitogen-activated protein kinase in rat mesangial cells. AB - BACKGROUND: Oxidative Stress and p38 mitogen-activated protein kinase (p38MAPK) play a vital role in renal fibrosis. Pioglitazone can protect kidney but the underlying mechanisms are less clear. The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK. METHODS: Rat mesangial cells were cultured and randomly assigned to control group, high glucose group and pioglitazone group. After 48-hour exposure, the supernatants and cells were collected. The protein levels of p22(phox), p47(phox), phosphorylated p38MAPK, total p38MAPK were measured by Western blotting. The gene expressions of p22(phox), p47(phox) were detected by RT-PCR. The levels of intracellular reactive oxygen species (ROS) were determined by flow cytometry. The levels of superoxide dismutase (SOD) and maleic dialdehyde (MDA) in the supernatant were determined respectively. RESULTS: Compared with the control group, the expression levels of p22(phox), p47(phox), phospho-p38 and ROS significantly increased, activity of SOD decreased in high glucose group, while the level of MDA greatly increased (P < 0.01). Pioglitazone significantly suppressed p22(phox), p47(phox) expressions and oxidative stress induced by high glucose. The expressions of p22(phox), p47(phox), phospho-p38MAPK and ROS generation were markedly reduced after pioglitazone treatment (P < 0.05). The activity of SOD in the the supernatant increased (P < 0.05), while the level of MDA decreased greatly by pioglitazone (P < 0.05). The level of oxidative stress was associated with the phosphorylation level of p38MAPK (P < 0.01). CONCLUSION: Pioglitazone can inhibit oxidative stress through suppressing NADPH oxidase expression and p38MAPK phosphorylation. PMID- 24229674 TI - Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial. AB - BACKGROUND: Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention. METHODS: This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules. The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded. The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups. Comparison of median values between two groups was done by the Student t test, one-way analysis of variance (ANOVA), or non-parametric rank sum test. RESULTS: A total of 310 patients were enrolled, 192 patients in the treatment group and 118 patients in the control group. Compared to the control group, the treatment group showed favorable outcomes in the Fg level, carotid IMT, the detection rate of vulnerable plaques, the volume of carotid plaques, NIHSS scores, and incidence of total vascular (6.78% and 2.08%, respectively) and cerebral vascular events (5.93% and 1.04%, respectively) (P < 0.05). In the treatment group, the volume of carotid plaques was significantly related to the carotid IMT, the plaque diameter, width and number (P = 0.000, 0.000, 0.000, 0.022; F = 13.51, 2.52, 11.33, -3.29, but there was a weak correlation with the Fg level (P = 0.056). After 1-year therapy, the incidence of overall vascular end points was reduced by 4.7%. CONCLUSION: Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention. PMID- 24229675 TI - Differences in the population of genetics of Mycobacterium tuberculosis between urban migrants and local residents in Beijing, China. AB - BACKGROUND: Currently, migration has become one of the risk factors of high burden of tuberculosis in China. This study was to explore the influence of mass migration on the dynamics of Mycobacterium (M.) tuberculosis in Beijing, the capital and an urban area of China. METHODS: Three hundred and thirty-six M. tuberculosis strains from the Changping district, where the problem of urban migrants was more pronounced than in other Beijing regions, were genotyped by Spoligotyping, large sequence polymorphisms (LSPs 105 and 181), and variable number tandem repeat (VNTR) typing. Based on the genotype data, the phylogeny of the isolates was studied. RESULTS: In Changping district, the proportion of Beijing lineage M. tuberculosis isolates amounted to 89.0% (299/336), among which 86.6 % (252) belonged to the modern lineage. The frequency of modern Beijing lineage strains is so high (around 75% (252/336)) that associated risk factors affecting the tuberculosis epidemic cannot be determined. The time to the most recent common ancestor (TMRCA) of the Beijing lineage strains was estimated to be 5073 (95% CI: 4000-6200) years. There was no significant difference in the genetic variation of Beijing isolates from urban migrants and local residents. CONCLUSIONS: The clone of modern Beijing lineage M. tuberculosis, which is dominant in the Beijing area, most likely started to expand with the five thousand-year-old Chinese civilization. In the future, with the urbanization in the whole of China, modern Beijing lineage M. tuberculosis may gain the larger geographical spread. PMID- 24229676 TI - Efficacy and tolerability of a single-pill combination of telmisartan/hydrochlorothiazide 80/25 mg in Chinese and Korean patients with moderate to severe hypertension: a subgroup analysis of a randomized, double blind, active-controlled trial. AB - BACKGROUND: Hypertension is an important issue in Asia, responsible for up to 66% of cardiovascular disease cases. This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) singlepill combination with T80 monotherapy, specifically in Chinese and Korean patients. METHODS: Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week, before uptitrating the dose to T80/H25 or T80, respectively, for the remaining 6 weeks. The primary endpoint was systolic blood pressure (SBP) mean change from baseline. Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline, and blood pressure (BP) goal achievement. Adverse events were recorded. RESULTS: Of a total 888 patients who were treated, efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80. At week 7, mean SBP reductions from baseline were -37.5 mmHg (1 mmHg = 0.133 kPa) and -26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference, -10.6 mmHg; 95% confidence interval (CI), -15.6 to -5.7). Mean DBP reductions were -19.0 and 14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference, -4.9 mmHg; 95% CI, -8.0 to -1.8). In total, 56.7% of patients receiving T80/H25 achieved BP goal (<140/90 mmHg) compared with 35.2% receiving T80. SBP goal attainment (<140 mmHg) and DBP goal attainment (<90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP: 69.3% vs. 48.1%; DBP: 62.2% vs. 46.3%). A small number of treatment-related adverse events were observed in both T80/H25 (nine patients, 6.9%) and T80 monotherapy (two patients, 3.6%) groups. CONCLUSIONS: In Chinese and Korean patients with moderate-to-severe hypertension, treatment with T80/H25 provided large reductions in mean SBP and DBP, and high BP goal attainment rates. This once-daily combination is effective and well tolerated in this patient group. PMID- 24229677 TI - Changes of cerebrospinal fluid pressure after thoracic endovascular aortic repair. AB - BACKGROUND: Decreasing the intracranial pressure has been advocated as one of the major protective strategies to prevent spinal cord ischemia after endovascular aortic repair. However, the actual changes of cerebrospinal fluid (CSF) pressure and its relation with spinal cord ischemia have been poorly understood. We performed CSF pressure measurements and provisional CSF withdrawal after thoracic endovascular aortic repair, and compared the changes of CSF pressure in high risk patients and in patients with new onset paraplegia and paraparesis. METHODS: Four hundred and nineteen patients were evaluated for the risk of spinal cord ischemia after thoracic endovascular aortic repair. Patients with identified risk factors before the procedure constituted group H and received prophylactic sequential CSF pressure measurement and CSF withdrawal. Patients who actually developed spinal cord ischemia constituted group P and received rescue CSF pressure measurements and CSF withdrawal. RESULTS: Among the 419 patients evaluated, 17 were graded as high risk. Four patients actually developed spinal cord ischemia after endovascular repair. The incidence of spinal cord ischemia in this investigation was 0.9%. The patients who actually developed spinal cord ischemia had no identified risk factors and had elevated CSF pressure, ranging from 15.4 to 30.0 mmHg. Six of the 17 patients graded as high risk had elevated CSF pressure: >20 mmHg in two patients and >15 mmHg in four patients. Sequential CSF pressure measurements and provisional withdrawal successfully decrease CSF pressure and prevented symptomatic spinal cord ischemia in high-risk patients. However, these measurements could only successfully reverse the neurologic deficit in two of the patients who actually developed spinal cord ischemia. CONCLUSIONS: Cerebrospinal fluid pressure was elevated in patients with spinal cord ischemia after thoracic endovascular aortic repair. Sequential measurements of CSF pressure and provisional withdrawal of CSF decreased CSF pressure effectively in high risk patients and provided effective prevention of spinal cord ischemia. Risk factor identification and prophylactic measurements play the key role in prevention of spinal cord ischemia after thoracic endovascular aortic repair. PMID- 24229678 TI - Postoperative diaphragmatic paralysis after cardiac surgery in children: incidence, diagnosis and surgical management. AB - BACKGROUND: Cardiac surgery for congenital heart disease covers a wide spectrum from simple to complex cardiac and extracardiac malformations. Innovations in pediatric cardiac surgery and perioperative care over the past decades have allowed surgical correction or at least palliation in almost all complex congenital heart defects in the first years of life. Diaphragmatic paralysis (DP) due to phrenic nerve injury after congenital cardiac surgery is an important respiratory complication resulting with respiratory insufficiency, lung infections, prolonged hospital stay time and even death. METHODS: Between April 2001 and December 2010, among patients undergoing cardiac surgery for congenital heart disease, postoperative DP was diagnosed in 47/10 200 (0.46%) patients. Diaphragmatic placation was performed in 37/47 patients. DP was suspected in children who failed to wean from mechanical ventilation or in those with persistent respiratory distress when there is no cardiac cause. Decreased respiratory sounds in auscultation, paradoxical breathing during spontaneous ventilation and elevated hemidiaphragm on chest X-ray led us to use fluoroscopy, ultrasound and/or electromyogram (EMG). When chest X-rays did not have a diagnostic value in patients with persistent respiratory distress, bilateral DP was suspected and immediate fluoroscopy of EMG was performed for diagnosis. In all patients, diaphragmatic placation was performed using a thoracic approach, through the sixth or seventh intercostals space with lateral thoracotomy. RESULTS: A total of 47 patients (21 females and 26 males) with a median age of 7.21 months (range 0.27-71 months) were diagnosed DP after cardiac surgery. The incidence of DP was 0.46% after cardiac surgery. The paralysed hemidiaphragm was left side in 26/47 (55.3%), right side in 17/47 (36.2%) and bilateral in 4/47 (8.5%) cases. The assisted ventilation time after cardiac surgery was (450+/-216) (116-856) hours. The median time from cardiac surgery to surgical placation was (24+/-14) (5-56) days. No patient died in this study. The follow-up period was (26.2+/-16.8) months. The position of the plicated diaphragm was normal on chest X-ray, in all plicated survivors within the 1st, 6th and 12th months after discharge. CONCLUSIONS: DP caused by phrenic nerve injury during surgical intervention for congenital heart disease is an important risk factor in terms of morbidity during the postoperative period. Diaphragmatic placation appears a good option, especially in newborns and small children, to wean patients from mechanical ventilation and to prevent long-term side effects of mechanical ventilation. PMID- 24229679 TI - Granulocyte colony-stimulating factor regulates JNK pathway to alleviate damage after cerebral ischemia reperfusion. AB - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against cerebral ischemia injury, but the molecular mechanisms have been unclear. This study aimed to investigate the influences of a short-acting (half-life 3.5 hours) G-CSF and a long-acting (half-life 40 hours) pegylated G-CSF on the JNK signaling pathway after cerebral ischemia reperfusion. METHODS: A total of 52 Sprague-Dawley rats were randomly divided into four groups: a sham group (n = 4), a vehicle with saline (n = 16), a short-acting G-CSF treatment group (n = 16) and a long-acting G-CSF treatment group (n = 16). The cerebral ischemia reperfusion model was established for the sham group and G-CSF treatment groups by middle cerebral artery occlusion (MCAO). Five days post reperfusion, rats were sacrificed and the brains were removed. Changes in neurological function after cerebral ischemia reperfusion was evaluated according to Neurological Severity Score (NSS) and the lesion volume and infarct size were measured by 2,3,5-triphenyltetrazolium chloride staining. The numbers of apoptotic neurons in these ischemic areas: left cerebral cortex, striatum and hippocampus were calculated by TUNEL assay, and expression of JNK/P-JNK, c-jun/P-c-jun in these areas was detected by Western blotting. RESULTS: Compared with the saline vehicle group ((249.68+/-23.36) mm(3), (19.27+/-3.37)%), G-CSF-treated rats revealed a significant reduction in lesion volume (long-acting: (10.89+/-1.90)%, P < 0.01; short-acting G-CSF: (11.69+/-1.41)%, P < 0.01) and infarct size (long-acting: (170.53+/-18.47) mm3, P < 0.01; short-acting G-CSF: (180.74+/-16.93) mm3, P < 0.01) as well as less neuron functional damage (P < 0.01) and a smaller number of apoptotic neurons in ischemic areas (P < 0.01). The activity of P-JNK and P-c-jun in the cerebral ischemia reperfusion-damaged cortex and hippocampus was significantly decreased in all G-CSF-treated rats (P < 0.05). However, between the long-acting and short acting G-CSF sets, there were no significant differences found in the activity of P-JNK and P-c-jun in the cortex, hippocampus and striate body (P > 0.05). CONCLUSIONS: Hypodermic injection of 50 ug/kg G-CSF attenuated the damage caused by cerebral ischemia reperfusion in rats, which might be associated with down regulated activation of the P-JNK and P-c-jun pathway after cerebral ischemia reperfusion. Long-acting G-CSF may be a novel choice for both clinical and basic research in treating cerebral ischemia. PMID- 24229680 TI - Persistent asthma increases the risk of chronic kidney disease: a retrospective cohort study of 2354 patients with asthma. AB - BACKGROUND: Chronic kidney disease (CKD) is a growing public health problem with well-established risk factors. Other contributing factors, however, remain to be identified. Systemic inflammation in asthma plays a significant role in the development of other diseases. We therefore initiated a study to assess whether the growing prevalence of asthma is associated with an increase in the risk of CKD. METHODS: We conducted a retrospective cohort study using data from 3015 patients with asthma aged 14 years and older who were registered and followed up in Asthma Control Study at the Department of Respiratory Medicine of three medical centers from 2005 to 2011. History, asthma control test (ACT), and asthma stage were used to assess the traits of asthma. CKD was defined as proteinuria and/or reduced estimated glomerular filtration rate (eGFR) (<60 ml*min(-1)*1.73 m(-2)) in two consecutive follow-up surveys. We used logistic regression models, adjusting for age, sex, and other confounding factor to determine associations between the traits of asthma and CKD. Kaplan-Meier curves were used to analyze patient outcomes. RESULTS: A total of 2354 subjects with complete data were recruited for this study with mean age (45.4+/-10.4) years. After 6 years of follow-up, 9.6% (n = 227) of the analytic cohort developed proteinuria and 3.1% (n = 72) progressed to eGFR <60 ml*min(-1)*1.73 m(-2). The patients with >20 years asthma history, not well-controlled or persistent asthma patients had higher incidence of proteinuria and reduced eGFR compared with patients with <=20 years asthma history, at least well-controlled or remission asthma, respectively. The multivariable adjusted OR for proteinuria and reduced eGFR in participants with persistent asthma was 1.49; (95% confidence interval (CI) 1.17-1.91) and 2.07 (95% CI 1.34-4.42). Compared to patients with no asthma traits, there was a significant risk (OR, 3.39; 95% CI 1.36-8.73) for those who met all three traits, including asthma history >20 years, not well-controlled and persistent stage, after adjusting for potential confounding factors. CONCLUSIONS: In this retrospective cohort study, we found that persistent asthma was associated with an increased risk of CKD, which was independent of obesity, diabetes, hypertension, and other well-established risk factors. Future studies should be directed to elucidate the mechanisms underlying the association between asthma and CKD. PMID- 24229681 TI - Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission. AB - BACKGROUND: Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood. METHODS: We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting. RESULTS: SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment. CONCLUSIONS: SNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1. PMID- 24229682 TI - Clinical analysis and risk stratification of ventricular septal rupture following acute myocardial infarction. AB - BACKGROUND: Ventricular septal rupture (VSR) remains an infrequent but devastating complication of acute myocardial infarction (AMI). The best time to undergo surgical repair is controversial and there is currently no risk stratification for patients with VSR to guide treatment. The purpose of this study was to review the clinical outcomes of 70 patients with VSR, to analyze the short-term prognosis factors of VSR following AMI, and to make a risk stratification for patients with VSR. METHODS: A total of 70 consecutive VSR patients following AMI treated in our hospital from January 2002 to October 2010 were enrolled in this study retrospectively. The difference of clinical characteristics were observed between patients with VSR who survived <=30 days and survived >30 days. We analyzed the short-term prognosis factors of VSR and established the short-term prognosis index of VSR (SPIV) based on the Logistic regression analysis to stratify patients with VSR. RESULTS: Among 12 354 patients with acute ST-segment elevation myocardial infarction, 70 (0.57%) patients (33 males and 37 females) were found to have VSR. The average age was (68.1+/-8.5) years. Fifty-four (77.1%) patients were diagnosed with an acute anterior infarction. Patients with VSR selected for surgical repair had better outcomes than patients treated conservatively; 1-year mortality 9.5% versus 87.8%, P < 0.005. Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-ventricular aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for shortterm mortality. SPIV >=9 indicates a high risk as the 30-day mortality is 77.4%; SPIV <8 indicates a low risk as the 30-day mortality is 28.6%; SPIV between 8 and 9 indicates a moderate risk. CONCLUSIONS: VSR remains a rare but devastating complication of AMI. The independent risk determinants for short-term mortality of VSR were female gender, anterior AMI, non-ventricular aneurysm, non-diabetes, Killip class 3 or 4, and the time from AMI to VSR less than 4 days. It is reasonable to take more active treatments for the patients at high risk to save more lives. PMID- 24229683 TI - A preliminary study of genes related to concomitant chemoradiotherapy resistance in advanced uterine cervical squamous cell carcinoma. AB - BACKGROUND: Tumor intrinsic chemoradiotherapy resistance is the primary factor in concomitant chemoradiotherapy failure in advanced uterine cervical squamous cell carcinoma. This study aims to identify a set of genes and molecular pathways related to this condition. METHODS: Forty patients with uterine cervical squamous cell carcinoma in International Federation of Gynecology and Obstetrics stage IIb or IIIb, treated with platinum-based concomitant chemoradiotherapy between May 2007 and December 2012, were enrolled in this trial. Patients included chemoradiotherapy resistant (n = 20) and sensitive (n = 20) groups. Total RNA was extracted from fresh tumor tissues obtained by biopsy before treatment and microarray analysis was performed to identify genes differentially expressed between the two groups. RESULTS: Microarray analysis identified 108 genes differentially expressed between concomitant chemoradiotherapy resistant and sensitive patients. Functional pathway cluster analysis of these genes revealed that DNA damage repair, apoptosis, cell cycle, Map kinase signal transduction, anaerobic glycolysis and glutathione metabolism were the most relevant pathways. Platelet-derived growth factor receptor alpha (PDGFRA) and protein kinase A type 1A (PRKAR1A) were significantly upregulated in the chemoradiosensitive group, while lactate dehydrogenase A (LDHA), bcl2 antagonist/killer 1 (BAK1), bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), and cyclin-dependent kinase 7 (CDK7) were upregulated in the chemoradiotherapy resistant group. CONCLUSION: We have identified seven genes that are differentially expressed in concomitant chemoradiotherapy resistant and sensitive uterine cervical squamous cell carcinomas, which may represent primary predictors for this condition. PMID- 24229685 TI - Patients after colostomy: relationship between quality of life and acceptance of disability and social support. AB - BACKGROUND: The aim of this research was to explore quality of life (QOL) and acceptance of disability and social support of colostomy patients as well as the relationship between these factors. METHODS: A descriptive, correlational study was conducted using four scales: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Colorectal Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-CR38) scales, the Acceptance of Disability Scale (ADS), and the Social Relational Quality Scale (SRQS). A convenience sample of 111 colostomy patients from four hospitals in Guangzhou who underwent colostomy operation at least one month prior to the study and who visited the stoma clinic or association from August 2011 to February 2012 was evaluated for inclusion in the study. All statistical analyses were performed using SPSS 17.0 software (SPSS Inc., Chicago, IL, USA). RESULTS: The patients' general health status was better than the reference level recommended by European Organization for Research and Treatment of Cancer, and the overall ADS score was average. The SRQS score was similar to that found in a Hong Kong study. The general health status and dimensions of QOL were significantly correlated with ADS and all of its dimensions (P < 0.05). The general health status and dimensions of QOL were also significantly correlated with SRQS and all of its dimensions (P < 0.05). CONCLUSIONS: QOL, acceptance of disability, and social relational quality of colostomy patients were closely related. Our results emphasize that patients should work to form rational values and close bonds with families and friends to achieve a better QOL. PMID- 24229684 TI - Reversion effects of curcumin on multidrug resistance of MNNG/HOS human osteosarcoma cells in vitro and in vivo through regulation of P-glycoprotein. AB - BACKGROUND: P-glycoprotein (P-gp) encoded by ATP-binding cassette sub-family B member 1 (ABCB1) gene is a kind of ATP-dependent drug transporter, which plays important roles in multidrug resistance (MDR) of human cancers, such as osteosarcoma. Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma longa, which is proved to possess antitumor biological activities including reversion of MDR. However, the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear. METHODS: We established a human osteosarcoma drug-resistant cell line MNNG/HOS/MTX by pulse exposure to methotrexate (MTX) and verified that the new cell lines were cross resistant to other anticancer agents. Then, according to the cytotoxicity assay, we reversed MDR of MNNG/HOS/MTX by 30 umol/L curcumin, and detected the mechanisms of curcumin reversing MDR through Real-time PCR, Western blotting assay, and Rhodamine123 (Rh123) transport test. Finally, we evaluated the effect of curcumin reversing MDR in vivo by MNNG/HOS/MTX cells xenograft-nude mice model. RESULTS: MNNG/HOS/MTX was proved to be a human osteosarcoma MDR cell line. MTT tumor chemosensitivity test indicates that 30 umol/L curcumin attenuates the half maximal inhibitory concentration (IC50) and resistance index (RI) to MTX, diamminedichloroplatinum (DDP), adriamycin (ADM), ifosfamide (IFO), and epirubicin (EPI) in MNNG/HOS/MTX cells (P < 0.05). Real-time PCR and Western blotting assays demonstrated that curcumin down-regulated P-gp expression of MNNG/HOS/MTX cells. Rh123 transport test showed that curcumin inhibited the transport function of P-gp in vitro. In vivo studies showed that curcumin displayed the features of sensitizing antitumor drugs and inhibiting the proliferation, invasion, and metastasis of osteosarcoma MDR cells. CONCLUSION: Down-regulation of P-gp and inhibition of the function of P-gp efflux pump may contribute to MDR reversion induced by curcumin in vitro and in vivo. PMID- 24229686 TI - Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells. AB - BACKGROUND: Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study. METHODS: Oxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells. RESULTS: Cell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3beta was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3beta. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3beta after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment. CONCLUSION: Ubiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells. PMID- 24229687 TI - Prognostic value of lymph node ratio in hypopharyngeal squamous cell carcinoma after chemoradiotherapy. AB - BACKGROUND: Lymph node ratio (LNR) has recently been reported as a potential prognostic marker in many malignant diseases. We aimed to analyze the potential prognostic effect of LNR on hypopharyngeal squamous cell carcinoma (HPSCC) after neoadjuvant therapy in our institution. METHODS: We performed a retrospective study of 279 patients with HPSCC who underwent radiotherapy with or without chemotherapy followed by neck dissection between November 1965 and December 2008. Patients were divided into four groups according to quartiles based on LNR. RESULTS: The mean LNR was 10.4% (range 0-100%, median 4.3%). Males and advanced clinical N classification significantly increased the LNR (P = 0.014 and P < 0.001, respectively). Compared with those with LNR <0.14, LNR >=0.14 was associated with reduced overall, disease-specific and disease-free survival (all at P < 0.001). Multivariate analysis revealed that LNR is an independent predictor of prognosis. CONCLUSION: Our results suggest that LNR is a strong predictor of HPSCC after chemoradiotherapy. PMID- 24229688 TI - Recombinant human thrombopoietin in combination with cyclosporin A as a novel therapy in corticosteroid-resistant primary immune thrombocytopenia. AB - BACKGROUND: The management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP. METHODS: Thirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 ug/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 ug/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn. RESULTS: There was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P > 0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P > 0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P < 0.05), second (29.4% vs. 68.8%, P < 0.05) and the third month (29.4% vs. 87.5%, P < 0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild. CONCLUSIONS: Combination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP. PMID- 24229689 TI - Difference of dilation resistance to coronary stenting between fibrous plaques and lipid-rich plaques. AB - BACKGROUND: Dilation resistance to stenting in non-calcified coronary plaques was compared in patients with percutaneous coronary intervention (PCI) in order to confirm the clinical usefulness of multislice computed tomography in examining coronary plaque type and to provide information pertaining to the effects of plaque type on dilatation resistance. METHODS: A retrospective analysis of 64 slice computed tomography coronary imaging data collected in the month prior to coronary stenting in 93 patients (65 male and 28 female, mean age of (57.22+/ 7.22) years) was conducted. Non-calcified coronary plaques were divided into lipid-rich (lipid content >25% of plaque volume) and fibrous plaques according to the Hammer-Hansen S method: where lipids, fiber, and intraluminal components were indicated by contrast using Hu values of -100-49, 50-129, and >130, respectively. Clinical features, pre-dilatation balloon specifications and filling pressure, and stent size and release pressure were compared. RESULTS: High-sensitivity C reactive protein levels were higher in the lipid-rich plaque group. In patients with typical symptoms, unstable angina was more commonly observed in the lipid rich plaque group. No significant differences in low density lipoprotein, pre dilatation balloon specifications, pre-dilatation pressure, or stent specifications were observed. Stent release pressure in the lipid-rich plaque group ((1130.16+/-202.04) kPa), was significantly lower than that observed in the fibrous plaque group ((1240.61+/-193.29) kPa, P = 0.009). CONCLUSION: Softer, lipid-rich plaques exhibit lower dilation resistance during stenting in PCI patients. PMID- 24229690 TI - Role of Lactobacillus in the prevention of Clostridium difficile-associated diarrhea: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is a major public health problem because of significant morbidity and mortality, and many clinicians pay attention to Lactobacillus as a potentially effective treatment. The purpose of this meta-analysis was to evaluate the efficacy of Lactobacillus in the prevention of CDAD. METHODS: The databases MEDLINE, the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, National Institutes of Health, CNKI, VIP, and Wanfang data were searched to locate all reported randomized controlled trials (RCT) from 1990 to December 2012. Only RCT in English and Chinese using Lactobacillus for the prevention of documented CDAD were considered for study inclusion. The data was analyzed by Review Manager and SPSS software. RESULTS: Seven placebo-controlled RCTs that evaluated the prevention of CDAD, which included 1486 subjects, accorded with inclusion and exclusion criteria. The mean age of the subjects ranged from 4.15 to 64.75 years and the proportion of male subjects ranged from 42.0% to 59.1%. The total daily dose of Lactobacillus ranged from 1.2*10(9)-1.2*10(12) colonyforming units (CFU). A low risk of bias was attributed to two studies and four studies evaluated a medium-level risk of bias. The combined risk ratio (RR) of developing CDAD was significantly lower in subjects who received Lactobacillus compared with subjects who received placebo (RR 0.38, 95% confidence interval (CI) 0.22-0.67). A combination regimen of Lactobacillus acidophilus (L. acidophilus) and Lactobacillus casei (L. casei) (RR 0.05, 95% CI 0.01-0.36) showed significant effect sizes for the prevention of CDAD, while single regimens of Lactobacillus plantarum (L. plantarum) and Lactobacillus rhamnosus (L. rhamnosus) did not. Across all trials, positive significant effects of Lactobacillus were observed in the elderly subgroup (RR 0.05, 95% CI 0.01-0.36). Whether the 1*10(12)-9*10(12) CFU/d Lactobacillus could prevent CDAD significantly or not was unclear. CONCLUSION: There is a sufficient evidence to recommend Lactobacillus (L. acidophilus and L. casei) as a prevention therapy for CDAD. PMID- 24229691 TI - Glycation of high-density lipoprotein in type 2 diabetes mellitus. AB - OBJECTIVE: To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property. DATA SOURCES: Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013, with keywords "glycation", "HDL", and "atherosclerosis". Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified, retrieved and reviewed. RESULTS: Glycation alters the structure of HDL and its associated enzymes, resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients. CONCLUSION: Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes. PMID- 24229692 TI - Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index. AB - OBJECTIVE: To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens. DATA SOURCES: We searched databases for primary studies published in English. The main search concepts were type 2 diabetes, insulin treatment, premixed insulin, premixed insulin analogs, basal inuslin, basal inuslin analogs, bolus insulin, bolus insulin analogs, safety and efficacy. STUDY SELECTION: Studies were eligible for inclusion if they met all of the following criteria: (1) type 2 diabetic patients aged >18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated. RESULTS: When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 100%, the proportion of GSCIDeltaA1c ratio more than 1 was 94.44%. When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 45.5%, the proportion of GSCIDeltaA1c ratio more than 1 was 38.9%. When premixed insulin therapy compared with oral hypoglycemic agents, the proportion of GSCI%A1c ratio less than 1 was 100%, the proportion of GSCIDeltaA1c ratio more than 1 was 50%. When premixed insulin therapy compared with basal-bolus insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 37.5%, the proportion of GSCIDeltaA1c ratio more than 1 was 50%. CONCLUSION: According to the GSCI ratio, long-acting basal insulin therapy tended to be superior to NPH therapy, oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy, noninsulin antidiabetic agents and premixed insulin therapy was comparable, and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes. PMID- 24229693 TI - Role of signaling pathways and miRNAs in chronic lymphocytic leukemia. AB - OBJECTIVE: To summarize the recent findings of dysregulation of signaling pathways and miRNAs in chronic lymphocytic leukemia (CLL). DATA SOURCES: We searched PubMed database with the keywords "chronic lymphocytic leukemia", "signal pathway", or "miRNA" for relevant articles in recent years. STUDY SELECTION: Research articles and reviews about signaling pathways and miRNAs in CLL were chosen for review. RESULTS: Dysregulation of signaling pathways, such as B cell receptor , toll-like receptor, PI3K, nuclear factor kappaB, notch signaling pathway, Wnt/Fzd signaling pathway, and Hedgehog and Janus kinases/signal transducers and activators of transcription signaling pathway, as the terminal events of the aberrant gene expression and the pro-survival effects of microenvironment, plays a crucial role in the process of CLL. miRNAs, a novel found noncoding RNA, which regulate gene expression at transcription or post transcription level and correlate with pathogenesis of CLL provide us new avenues to better evaluating prognosis and therapy of it. CONCLUSION: Further investigation of the dysregulation of signaling pathways and miRNAs and their relationship may provide us a new prospective to understand the pathogenesis of CLL and may provide us new strategies to resolve the clinical nodi in treatment of CLL. PMID- 24229694 TI - Coronary bypass grafting in Chinese patients dependent on maintenance dialysis. PMID- 24229695 TI - Propofol inhibits neuronal differentiation of mouse embryonic stem cells in vitro. PMID- 24229696 TI - Efficiency analysis of stenting for acute colorectal obstruction. PMID- 24229697 TI - A novel arg616Cys mutation in the DNA-binding domain of complete androgen insensitivity syndrome in a Chinese family. PMID- 24229698 TI - Clinical variability in onset of influenza A (H7N9) infection. PMID- 24229699 TI - A case of metastatic scalp angiosarcoma presenting as multiple thin-walled lung cysts and pneumothorax. PMID- 24229700 TI - Severe mitral valve stenosis with left atrial thrombus in the puerperium: to treat or to observe? PMID- 24229701 TI - Renal denervation for "resistant ventricular tachycardia": a potential treatment option? PMID- 24229702 TI - Compulsivity, impulsivity, and the DSM-5 process. AB - Compulsivity and impulsivity are cross-cutting, dimensional symptom domains that span traditional diagnostic boundaries. We examine compulsivity and impulsivity from several perspectives and present implications for these symptom domains as they relate to classification. We describe compulsivity and impulsivity as general concepts, from the perspectives of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Research Planning Agenda, and from the DSM-5 workgroups, literature reviews, and field trials. Finally, we detail alternative modes of classification for compulsivity and impulsivity in line with the Research Domain Criteria (RDoC) and International Classification of Diseases (ICD-11). PMID- 24229703 TI - Sox4you: a new player in C/EBPalpha leukemia. AB - Although CEBPA mutations are among the most common genetic abnormalities in acute myeloid leukemia (AML), the transformation mechanism remains largely obscure. In this issue of Cancer Cell, Zhang and colleagues report that SOX4 is a direct target and crucial mediator of C/EBPalpha mutants in AML, revealing a potential therapeutic avenue. PMID- 24229704 TI - A new twist on radiation oncology: low-dose irradiation elicits immunostimulatory macrophages that unlock barriers to tumor immunotherapy. AB - Tumor-infiltrating macrophages typically promote angiogenesis while suppressing antitumoral T cell responses. In this issue of Cancer Cell, Klug and colleagues report that clinically-feasible, low-dose irradiation redirects macrophage differentiation from a tumor-promoting/immunosuppressive state to one that enables cytotoxic T cells to infiltrate tumors and kill cancer cells, rendering immunotherapy successful in mice. PMID- 24229705 TI - Killing tumors by keeping ras and PI3' kinase apart. AB - Ras proteins mediate PI3K activation through direct binding to p110 catalytic subunits. However, it is unclear when and where this interaction occurs. In this issue of Cancer Cell, Castellano and colleagues report that KRAS-driven lung cancers require the Ras-p110alpha interaction for full activation of PI3K and tumor maintenance. PMID- 24229706 TI - To die or not to die: Sema3E rules the game. AB - Sema3E, a ligand for PlexinD1, controls angiogenesis and promotes cancer invasion and metastasis. In this issue of Cancer Cell, Luchino and colleagues report that Sema3E also ensures breast cancer cell viability by blocking a previously unknown proapoptotic signaling cascade elicited by unliganded PlexinD1, thus behaving as a "dependence receptor." PMID- 24229708 TI - Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma. AB - Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14(ARF)/p19(Arf) and p21(WAF/CIP). When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14(ARF) and p21(WAF/CIP) was prolonged. These results provide a missing link between oncogenic K-Ras and the p14(ARF)-p53 pathway, and may explain how cells defend against oncogenic K-Ras. PMID- 24229707 TI - Histone H3.3 mutations: a variant path to cancer. AB - A host of cancer types exhibit aberrant histone modifications. Recently, distinct and recurrent mutations in a specific histone variant, histone H3.3, have been implicated in a high proportion of malignant pediatric brain cancers. The presence of mutant H3.3 histone disrupts epigenetic posttranslational modifications near genes involved in cancer processes and in brain function. Here, we review possible mechanisms by which mutant H3.3 histones may act to promote tumorigenesis. Furthermore, we discuss how perturbations in normal H3.3 chromatin-related and epigenetic functions may more broadly contribute to the formation of human cancers. PMID- 24229709 TI - Requirement for interaction of PI3-kinase p110alpha with RAS in lung tumor maintenance. AB - RAS proteins directly activate PI3-kinases. Mice bearing a germline mutation in the RAS binding domain of the p110alpha subunit of PI3-kinse are resistant to the development of RAS-driven tumors. However, it is unknown whether interaction of RAS with PI3-kinase is required in established tumors. The need for RAS interaction with p110alpha in the maintenance of mutant Kras-driven lung tumors was explored using an inducible mouse model. In established tumors, removal of the ability of p110alpha to interact with RAS causes long-term tumor stasis and partial regression. This is a tumor cell-autonomous effect, which is improved significantly by combination with MEK inhibition. Total removal of p110alpha expression or activity has comparable effects, albeit with greater toxicities. PMID- 24229710 TI - CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. AB - A large body of evidence indicates that chronic inflammation is one of several key risk factors for cancer initiation, progression, and metastasis. However, the underlying mechanisms responsible for the contribution of inflammation and inflammatory mediators to cancer remain elusive. Here, we present genetic evidence that loss of CXCR2 dramatically suppresses chronic colonic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis-associated cancer. CXCR2 ligands were elevated in inflamed colonic mucosa and tumors and induced MDSC chemotaxis. Adoptive transfer of wild-type MDSCs into Cxcr2(-/-) mice restored AOM/DSS-induced tumor progression. MDSCs accelerated tumor growth by inhibiting CD8(+) T cell cytotoxic activity. PMID- 24229712 TI - Incidence and prevalence of Toxoplasma gondii infection in women in France, 1980 2020: model-based estimation. AB - Toxoplasmosis is a worldwide zoonosis due to Toxoplasma gondii, a ubiquitous protozoan parasite of warm-blooded animals including humans. In pregnant women, primary infection can cause congenital toxoplasmosis resulting in severe malformations in the newborn. Since 1978, public health authorities in France have implemented a congenital toxoplasmosis prevention programme, including monthly serological screening of all seronegative pregnant women, and treatment in case of seroconversion. However, this programme does not produce systematic surveillance data on incidence and prevalence. Our objective was to estimate the incidence and prevalence of T. gondii infection, and the incidence of seroconversion during pregnancy in women in France. We used a catalytic model to estimate incidence and prevalence of Toxoplasma infection between 1980 and 2020 in women of childbearing age. We used age- and time-specific seroprevalence data obtained from the National Perinatal Surveys (NPS) conducted in 1995, 2003 and 2010. We assumed that incidence depends both on age and calendar time, and can be expressed as the product of two unknown functions. We also estimated incidence of seroconversion during pregnancy in 2010 from the NPS and the National Surveillance of Congenital Toxoplasmosis (ToxoSurv). We combined data of 42208 women aged 15-45 years with serology available from the three NPS. For women aged 30 years the modelled incidence decreased from 7.5/1000 susceptible women in 1980 to 3.5/1000 in 2000. In 2010 the incidence was 2.4/1000. The predicted incidence and prevalence for 2020 was 1.6/1000 and 27%, respectively. The incidence of seroconversion during pregnancy in 2010 was estimated at 2.1/1000 susceptible pregnant women (95% CI 1.3-3.1) from the NPS and 1.9 (95% CI 1.8-2.1) from ToxoSurv. Incidence and prevalence of Toxoplasma infection has decreased markedly during the last 30 years. This decrease may be explained by a lower exposure to the parasite by changes in food habits and by improved hygiene practices in meat production. Modelled estimations were consistent with estimates observed in other studies conducted previously in France. The catalytic modelling provides reliable estimates of incidence and prevalence of Toxoplasma infection over time. This approach might be useful for evaluating preventive programme for toxoplasmosis. PMID- 24229711 TI - Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. AB - pRb and p53 are two major tumor suppressors. Here, we found that p53 activates expression of Pirh2 and KPC1, two of the three ubiquitin ligases for p27. Loss of p53 in the absence of Skp2, the third ubiquitin ligase for p27, shrinks the cellular pool of p27 ubiquitin ligases to accumulate p27 protein. In the absence of pRb and p53, p27 was unable to inhibit DNA synthesis in spite of its abundance, but could inhibit division of cells that maintain DNA replication with rereplication. This mechanism blocked pRb/p53 doubly deficient pituitary and prostate tumorigenesis lastingly coexistent with bromodeoxyuridine-labeling neoplastic lesions, revealing an unconventional cancer cell vulnerability when pRb and p53 are inactivated. PMID- 24229713 TI - Effects of repeated consumption on sensory-enhanced satiety. AB - Previous research has suggested that sensory characteristics of a drink modify the acute satiating effects of its nutrients, with enhanced satiety being evident when a high-energy drink was thicker and tasted creamier. The present study tested whether this modulation of satiety by sensory context was altered by repeated consumption. Participants (n 48) consumed one of four drinks mid-morning on seven non-consecutive days, with satiety responses being measured pre-exposure (day 1), post-exposure (day 6) and at a 1-month follow-up. The drinks combined two levels of energy (lower energy (LE), 326 kJ and higher energy, 1163 kJ) with two levels of satiety-predictive sensory characteristics (low sensory (LS) or enhanced sensory). Test lunch intake 90 min after drink consumption depended on both the energy content and sensory characteristics of the drink before exposure, but on the energy content alone after exposure and at the follow-up. The largest change was an increase in test meal intake over time in the LE/LS condition. The effects on intake were reflected in appetite ratings, with rated hunger and expected filling affected by sensory characteristics and energy content pre exposure, but were largely determined by energy content post-exposure and at the follow-up. In contrast, a measure of expected satiety reflected sensory characteristics regardless of energy content on all the three test days. Overall, these data suggest that some aspects of the sensory modulation of satiety are changed by repeated consumption, with covert energy becoming more effective in suppressing appetite over time, but also suggest that these behavioural changes are not readily translated into expectations of satiety. PMID- 24229714 TI - Gamete quality in fish: evaluation parameters and determining factors. AB - The quality of fish gametes, both male and female, are determined by several factors (age, management, feeding, chemical and physical factors, water quality, etc.) that have an impact on the survivability of embryos, larvae and/or fry in the short or long term. One of the most important factors is gamete ageing, especially for those species that are unable to spawn naturally in hatcheries. The chemical and physical factors in hatcheries and the nutrition that they provide can significantly alter harvest quality, especially from females; as a rule, males are more tolerant of stress conditions produced by inadequate feeding, management and/or poor water conditions. The stress produced on broodstock by inadequate conditions in hatcheries can produce adverse effects on gamete quality, survival rates, and the embryonic eggs after hatching. PMID- 24229715 TI - Influence of energy and nutrient supply pre and post partum on performance of multiparous Simmental, Brown Swiss and Holstein cows in early lactation. AB - A study was conducted to evaluate the effects of pre partum (PRE) and post partum (POST) dietary energy and nutrient supply (E) and their interactions on feed intake, performance and energy status in dairy cows of three breeds. In this experiment, the effects of three energy and nutrient supply levels (low (L), medium (M), high (H)), both pre-calving and post-calving, were investigated, using a 3*3 factorial arrangement of treatments. In both phases (84 days pre- and 105 days post-calving) E levels applied to a total of 81 multiparous cows of breeds Simmental (SI), Brown Swiss (BS) and Holstein-Friesian (HF; n=27 for each breed), were 75%, 100% and 125% of recommendations of the German Society of Nutrition Physiology (GfE). Dry matter intake (DMI) was restricted, if energy intake exceeded target values. Pre partum DMI and energy intake were different as designed, liveweight and body condition score (BCS) of SI cows were higher, but EB was lower, compared to BS and HF cows. Milk yield and composition were influenced by all three main experimental factors (EPRE, EPOST, breed). Energy corrected milk yield was 25.6, 28.6 and 30.1 kg/day for LPRE, MPRE and HPRE as well as 21.5, 30.1 and 32.6 kg/day for LPOST, MPOST and HPOST, respectively. Numerically, only for milk protein content the interactions EPRE*EPOST and EPRE*breed reached significance. Impact of energy supply pre-calving was more pronounced when cows had lower energy supply post-calving and vice versa. On the other hand, milk yield response of cows to energy supply above requirements was greater for cows that were fed on a low energy level pre partum. Impact of energy level pre partum was higher for HF cows, showing that their milk production relies to a greater extent on mobilization of body reserves. Increasing energy supply pre partum led to a more negative energy balance post partum, mainly by increasing milk yield and content, whereas feed intake was slightly reduced. Increasing energy supply post partum enhanced milk yield as well as milk protein and lactose content. Calculated energy balance corresponded well with liveweight and BCS change. Response of milk yield to increasing energy supply followed the principle of diminishing returns, since energy was increasingly partitioned to body retention. Increasing energy supply pre partum enhances milk yield and content post partum, but exacerbates negative energy balance and its consequences. PMID- 24229717 TI - Burden of human papillomavirus infection and related diseases in Israel. AB - This manuscript provides the available data on the burden of human papillomavirus (HPV) infections and HPV-related diseases in Israel. The incidence of cervical intraepithelial neoplasia grade 3 (CIN3) among Jewish women was 17.4 per 100,000 in 2007, showing an increase since 1997. The incidence of cervical cancer was 5.3 per 100,000 Israeli Jewish women and 2.3 per 100,000 Israeli non-Jewish women in 2007. This rate is relatively low compared to other developed countries, and could be explained by cultural and religious factors such as male circumcision or sexual behavior. Mortality rates were around 1.5 per 100,000 Israeli women in 2007. Incidences of other anogenital, oral cavity, and pharynx cancers are very low, below 1.0 per 100.000 Israeli women and men. Information is scarce on HPV prevalence and HPV type distribution among women with cervical cancer. HPV types 16 and 18 were the two most common types in both preneoplastic lesions and cervical cancer, representing 60% of total invasive cases. Data on genital warts show an incidence rate of 239 per 100,000 men and 185 per 100,000 women, similar to that found in other Western countries. Despite these low incidences, it is important to improve the information on the overall burden of HPV-related morbidity and on the HPV prevalence to evaluate an organized cervical cancer screening program and the introduction of the HPV vaccine in the national school based vaccine program. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID- 24229718 TI - Cervical cancer screening, human papillomavirus vaccination practices and current infrastructure in Israel. AB - The incidence rates for premalignant lesions in Jewish women in Israel are similar to those observed in Western countries, but the incidence of cervical cancer in Israel is low; this discrepancy is not yet clearly understood. Because of the low incidence of cervical cancer in Israel, it was decided to base cervical cancer prevention on opportunistic screening: every woman from the ages of 35-54 years can have a Pap test smear free of charge every 3 years. Over the last decade 12.2% of the women population had an annual Pap test. From 36 to 50% of women who attended the Clalit Health Maintenance Organization (HMO) and the Maccabi HMO, the two largest HMOs in Israel, did so. There were also discrepancies between women of different socio-economic status (SES): <10% in the lowest SES level were screened compared to almost 55% in the higher level. HPV vaccination was opportunistic but it will be introduced to the school-based vaccine program at age of 13 years old as of September 2013. The Israel Society of Obstetrics and Gynecology recommends continuing cytologic screening in vaccinated women as recommended for the general population. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID- 24229719 TI - Cost-utility analysis of interventions to reduce the burden of cervical cancer in Israel. AB - Using World health Organization, CHOosing Interventions that are Cost Effective (WHO-CHOICE) methodology, cost-utility ratios were calculated for various interventions (Papanicolaou [Pap] smear, human papillomavirus [HPV]-DNA testing, visual inspection with acetic acid [VIA] and vaccination against HPV) at various frequencies to reduce the burden of cervical cancer and condyloma (in the case of the HPV vaccination) in Israel, which has a low prevalence of cervical cancer. All of the screening and/or vaccine interventions were very cost-effective. Attempts should be made to raise compliancy with Pap smears from the current opportunistic 12.1% per annum to screen everyone aged 20-64 once every 5 years in combination with HPV-DNA testing for persons aged 30-64 both before and/or after HPV vaccination is introduced. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID- 24229716 TI - Comprehensive control of human papillomavirus infections and related diseases. AB - Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. PMID- 24229720 TI - Barriers to human papillomavirus vaccine acceptability in Israel. AB - Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immunity against only few virus types; the vaccine's high cost; and the perception that HPV transmission is associated with unacceptable sexual relations. A recent survey has demonstrated that, following media two campaigns, Israeli's level of awareness of the vaccine increased but the actual vaccination rate remained low, at approximately 10%. Survey findings also indicated that an enduring barrier to HPV vaccination is the vaccine's high cost. Recent research on a convenience sample of Israeli undergraduate women 21 to 24 years of age showed that intentions to receive HPV vaccination in the coming year were a function of women's attitudes towards getting vaccinated and their perceptions of social support for doing so. Undergraduate women who intended to be vaccinated perceived the prevention of cervical cancer, avoidance of personal health threat, and avoidance of HPV infection per se to be the advantages of undergoing HPV vaccination. Disadvantages of getting vaccinated included fear of vaccine side effects, cost of the vaccine, and newness of the vaccine, doubts about vaccines, time required to undergo multiple vaccinations, and dislike of injections. Friends', mothers' and physicians' recommendations influenced women's intentions to be vaccinated in the coming year as well. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID- 24229721 TI - Screening for cervical cancer and human papillomavirus vaccination in Israel: recommendations. PMID- 24229722 TI - Human papillomavirus-associated diseases in Israel--the controversy continues. Foreword. PMID- 24229723 TI - The path to eliminate cervical cancer in the world and the challenges of professional education. Preface. PMID- 24229724 TI - Blood parasites in noddies and boobies from Brazilian offshore islands - differences between species and influence of nesting habitat. AB - Seabirds are often free from blood parasites, and a recent review suggested that phylogenetic, ecological and life-history parameters can determine the prevalence of blood parasites in seabirds. However, there is a lack of data available from many seabird groups, and a larger database is needed to understand prevalence patterns of blood parasites. We used a molecular screening approach to detect parasites of the genera Plasmodium, Haemoproteus, Leucocytozoon and Babesia in five species of two genera of seabirds that breed on Atlantic Ocean islands off Brazil. The observed patterns differed between the two bird genera. Like other Laridae, brown noddy, Anous stolidus adults were infected with Haemoproteus with low prevalence. Masked boobies, Sula dactylatra and brown boobies, Sula leucogaster were infected with Babesia. Of the latter, mainly juveniles were infected. In all species, intensity of infection (i.e. number of infected erythrocytes) was so low that parasites remained undetected in blood smears. This may explain the absence of major effects on the body condition of birds, although infected juvenile masked boobies were lighter than juveniles that were not infected with Babesia. Two tree-nesting species; black noddy, Anous minutus and red-footed booby, Sula sula did not have blood parasites, suggesting that tree nesting may reduce the exposure to arthropod vectors compared with ground nesting in these species. PMID- 24229725 TI - Pharmacotherapy of cognitive deficits in schizophrenia. AB - While second-generation antipsychotics treat negative as well as positive symptoms, recovery for persons with schizophrenia remains elusive, in part because there are no FDA-approved medications that treat the cognitive deficits of schizophrenia (CDS). Recent work has identified agents that, when added to antipsychotics, improve cognition in schizophrenia. This work and hypothesized mechanisms of action will be reviewed. PMID- 24229726 TI - Rice and noodle consumption is associated with insulin resistance and hyperglycaemia in an Asian population. AB - High consumption of refined grains, particularly white rice, has been reported to be associated with a higher risk of type 2 diabetes. Therefore, in the present study, we evaluated the association between rice and noodle consumption and markers of glucose homeostasis, inflammation and dyslipidaemia in an Asian population. We carried out a population-based cross-sectional study in 2728 Singaporean Chinese men and women aged between 24 and 92 years. Rice and noodle intake was assessed using a validated FFQ and studied in relation to glycaemic (fasting glucose, glycated Hb, homeostasis model assessment (HOMA) index for insulin resistance (HOMA-IR) and HOMA index for beta-cell function (HOMA-beta)), inflammatory (plasma adiponectin and C-reactive protein (CRP)) and lipid (fasting TAG and HDL-cholesterol (HDL-C)) markers. We used multiple linear regression analyses with adjustment for total energy intake and sociodemographic, anthropometric (BMI and waist:hip ratio) and lifestyle factors. Higher rice consumption was found to be associated with higher fasting glucose concentrations (0.81 % higher values per portion increment; 95 % CI 0.09, 1.54) and HOMA-IR (4.62 %; 95 % CI 1.29, 8.07). Higher noodle consumption was also found to be significantly associated with higher fasting glucose concentrations (1.67 %; 95 % CI 0.44, 2.92), HOMA-IR (6.17 %; 95 % CI 0.49, 12.16) and fasting TAG concentrations (9.17 %; 95 % CI 3.44, 15.22). No significant association was observed between rice and noodle consumption and adiponectin, CRP and HDL-C concentrations or HOMA-beta in the fully adjusted model. These results suggest that high consumption of rice and noodles may contribute to hyperglycaemia through greater insulin resistance and that this relationship is independent of adiposity and systemic inflammation. PMID- 24229727 TI - Comparison of air samples, nasal swabs, ear-skin swabs and environmental dust samples for detection of methicillin-resistant Staphylococcus aureus (MRSA) in pig herds. AB - To identify a cost-effective and practical method for detection of methicillin resistant Staphylococcus aureus (MRSA) in pig herds, the relative sensitivity of four sample types: nasal swabs, ear-skin (skin behind the ears) swabs, environmental dust swabs and air was compared. Moreover, dependency of sensitivity on within-herd prevalence was estimated. spa-typing was applied in order to study strain diversity. The sensitivity of one air sample was equal to the sensitivity of ten pools of five nasal swabs and relatively independent of within-herd prevalence [predicted to be nearly perfect (99%) for within-herd prevalence ?25%]. The results indicate that taking swabs of skin behind the ears (ten pools of five) was even more sensitive than taking nasal swabs (ten pools of five) at the herd level and detected significantly more positive samples. spa types t011, t034 and t4208 were observed. In conclusion, MRSA detection by air sampling is easy to perform, reduces costs and analytical time compared to existing methods, and is recommended for initial testing of herds. Ear-skin swab sampling may be more sensitive for MRSA detection than air sampling or nasal swab sampling. PMID- 24229728 TI - Management factors affecting mortality, feed intake and feed conversion ratio of grow-finishing pigs. AB - The aim of this study was to determine the effect of animal management and farm facilities on total feed intake (TFI), feed conversion ratio (FCR) and mortality rate (MORT) of grower-finishing pigs. In total, 310 batches from 244 grower finishing farms, consisting of 454 855 Pietrain sired pigs in six Spanish pig companies were used. Data collection consisted of a survey on management practices (season of placement, split-sex by pens, number of pig origins, water source in the farm, initial or final BW) and facilities (floor, feeder, ventilation or number of animals placed) during 2008 and 2009. Results indicated that batches of pigs placed between January and March had higher TFI (P=0.006), FCR (P=0.005) and MORT (P=0.03) than those placed between July and September. Moreover, batches of pigs placed between April and June had lower MORT (P=0.003) than those placed between January and March. Batches which had split-sex pens had lower TFI (P=0.001) and better FCR (P<0.001) than those with mixed-sex in pens; pigs fed with a single-space feeder with incorporated drinker also had the lowest TFI (P<0.001) and best FCR (P<0.001) in comparison to single and multi-space feeders without a drinker. Pigs placed in pens with <50% slatted floors presented an improvement in FCR (P<0.05) than pens with 50% or more slatted floors. Batches filled with pigs from multiple origins had higher MORT (P<0.001) than those from a single origin. Pigs housed in barns that performed manual ventilation control presented higher MORT (P<0.001) in comparison to automatic ventilation. The regression analysis also indicated that pigs which entered to grower-finisher facilities with higher initial BW had lower MORT (P<0.05) and finally pigs which were sent to slaughterhouse with a higher final BW presented higher TFI (P<0.001). The variables selected for each dependent variable explained 61.9%, 24.8% and 20.4% of the total variability for TFI, FCR and MORT, respectively. This study indicates that farms can increase growth performance and reduce mortality by improving farm facilities and/or modifying management practices. PMID- 24229729 TI - Does peer learning or higher levels of e-learning improve learning abilities? A randomized controlled trial. AB - BACKGROUND AND AIMS: The fast development of e-learning and social forums demands us to update our understanding of e-learning and peer learning. We aimed to investigate if higher, pre-defined levels of e-learning or social interaction in web forums improved students' learning ability. METHODS: One hundred and twenty Danish medical students were randomized to six groups all with 20 students (eCases level 1, eCases level 2, eCases level 2+, eTextbook level 1, eTextbook level 2, and eTextbook level 2+). All students participated in a pre-test, Group 1 participated in an interactive case-based e-learning program, while Group 2 was presented with textbook material electronically. The 2+ groups were able to discuss the material between themselves in a web forum. The subject was head injury and associated treatment and observation guidelines in the emergency room. Following the e-learning, all students completed a post-test. Pre- and post-tests both consisted of 25 questions randomly chosen from a pool of 50 different questions. RESULTS: All students concluded the study with comparable pre-test results. Students at Level 2 (in both groups) improved statistically significant compared to students at level 1 (p>0.05). There was no statistically significant difference between level 2 and level 2+. However, level 2+ was associated with statistically significant greater student's satisfaction than the rest of the students (p>0.05). CONCLUSIONS: This study applies a new way of comparing different types of e-learning using a pre-defined level division and the possibility of peer learning. Our findings show that higher levels of e-learning does in fact provide better results when compared with the same type of e learning at lower levels. While social interaction in web forums increase student satisfaction, learning ability does not seem to change. Both findings are relevant when designing new e-learning materials. PMID- 24229730 TI - Are medical schools hesitant to teach undergraduate students teaching skills? A medical student's critical view. AB - Junior medical staff provides a large proportion of undergraduate student education. However, despite increasing numbers of resident-as-teacher training programs, junior doctors may still not be sufficiently prepared to teach medical students. Hence, medical schools should consider implementing formal teaching skills training into undergraduate curricula. PMID- 24229731 TI - Expression of phosphatidylcholine biosynthetic enzymes during early embryogenesis in the amphibian Bufo arenarum. AB - In the principal route of phosphatidylcholine (PC) synthesis the regulatory steps are catalysed by CTP:phosphocholine cytidylyltransferase (CCT) and choline kinase (CK). Knock-out mice in Pcyt1a (CCT gene) and Chka1 (CK gene) resulted in preimplantation embryonic lethality, demonstrating the essential role of this pathway. However, there is still a lack of detailed CCT and CK expression analysis during development. The aim of the current work was to study the expression during early development of both enzymes in the external-fertilization vertebrate Bufo arenarum. Reverse transcription polymerase chain reaction (RT PCR) and western blot confirmed their presence in unfertilized eggs. Analysis performed in total extracts from staged embryos showed constant protein levels of both enzymes until the 32-cell stage: then they decreased, reaching a minimum in the gastrula before starting to recover. CTP:phosphocholine cytidylyltransferase is an amphitropic enzyme that inter-converts between cytosolic inactive and membrane-bound active forms. Immunoblot analysis demonstrated that the cytosolic:total CCT protein ratio does not change throughout embryogenesis, suggesting a progressive decline of CCT activity in early development. However, PC (and phosphatidylethanolamine) content per egg/embryo remained constant throughout the stages analysed. In conclusion, the current data for B. arenarum suggest that net synthesis of PC mediated by CCT and CK is not required in early development and that supplies for membrane biosynthesis are fulfilled by lipids already present in the egg/embryo reservoirs. PMID- 24229732 TI - Motivational interviewing and decisional balance: contrasting responses to client ambivalence. AB - BACKGROUND: A recommendation in original descriptions of motivational interviewing (MI) was to "explore ambivalence". Contrasting procedures for doing so have been clarified through the evolution of MI. AIMS: This article describes two conceptually distinct methods for responding to ambivalence: decisional balance (DB) and MI's evocation of change talk, and reviews empirical evidence to recommend when each procedure is appropriate (and inappropriate) in clinical practice. METHOD: The authors summarize findings of clinical outcome research to examine how these two interventions impact the resolution of client ambivalence. RESULTS: With ambivalent people, a DB intervention tends to decrease commitment to change, whereas evocation (a key element of MI) promotes change. When a person has already made the decision to change, evocation is unnecessary and may deter change, whereas DB may further strengthen commitment. CONCLUSIONS: DB is an appropriate procedure when the clinician wishes to maintain neutrality and not favor the resolution of ambivalence in any particular direction. Evocation is appropriate when the clinician intends to help clients resolve ambivalence in the direction of change. PMID- 24229733 TI - Vertical transmission of Tetracapsuloides bryosalmonae (Myxozoa), the causative agent of salmonid proliferative kidney disease. AB - The freshwater bryozoan, Fredericella sultana, is the main primary host of the myxozoan endoparasite, Tetracapsuloides bryosalmonae which causes proliferative kidney disease (PKD) of salmonid fish. Because spores that develop in bryozoan colonies are infectious to fish, bryozoans represent the ultimate source of PKD. Bryozoans produce numerous seed-like dormant stages called statoblasts that enable persistence during unfavourable conditions and achieve long-distance dispersal. The possibility that T. bryosalmonae may undergo vertical transmission via infection of statoblasts has been the subject of much speculation since this is observed in close relatives. This study provides the first evidence that such vertical transmission of T. bryosalmonae is extensive by examining the proportions of infected statoblasts in populations of F. sultana on two different rivers systems and confirms its effectiveness by demonstrating transmission from material derived from infected statoblasts to fish hosts. Vertical transmission in statoblasts is likely to play an important role in the infection dynamics of both bryozoan and fish hosts and may substantially contribute to the widespread distribution of PKD. PMID- 24229734 TI - Profiling of the yak skeletal muscle tissue gene expression and comparison with the domestic cattle by genome array. AB - Of all the mammals of the world, the yak lives at the highest altitude area of more than 3000 m. Comparison between yak and cattle of the low-altitude areas will be informative in studying animal adaptation to higher altitudes. To investigate the molecular mechanism involved in meat quality differences between the two Chinese special varieties Qinghai yak and Qinchuan cattle, 12 chemical physical characteristics of the longissimus dorsi muscle related to meat quality were compared at the age of 36 months, and the gene expression profiles were constructed by utilizing the bovine genome array. Significant analysis of microarrays was used to identify the differentially expressed genes. Gene ontology and pathway analysis were performed by a free Web-based Molecular Annotation System 2.0. The results reveal ~11 000 probes representing about 10 000 genes that were detected in both the Qinghai yak and Qinchuan cattle. A total of 1922 genes were shown to be differentially expressed, 633 probes were upregulated and 1259 probes were downregulated in the muscle tissue of Qinghai yak that were mainly involved in ubiquitin-mediated proteolysis, muscle growth regulation, glucose metabolism, immune response and so on. Quantitative real-time PCR (qRT-PCR) was performed to validate some differentially expressed genes identified by microarray. Further analysis implied that animals living at a high altitude may supply energy by more active protein catabolism and glycolysis compared with those living in the plain areas. Our results establish the groundwork for further studies on yaks' meat quality and will be beneficial in improving the yaks' breeding by molecular biotechnology. PMID- 24229735 TI - Diets high in fermentable protein and fibre alter tight junction protein composition with minor effects on barrier function in piglet colon. AB - Protein fermentation end products may damage the colonic mucosa, which could be counteracted by dietary inclusion of fermentable carbohydrates (fCHO). Although fermentable crude protein (fCP) and fCHO are known to affect microbial ecology, their interactive effects on epithelial barrier function are unknown. In the present study, in a 2 * 2 factorial experiment, thirty-two weaned piglets were fed low-fCP/low-fCHO (14.5 % crude protein (CP)/14.5 % total dietary fibre (TDF)), low-fCP/high-fCHO (14.8 % CP/16.6 % TDF), high-fCP/low-fCHO (19.8 % CP/14.5 % TDF) and high-fCP/high-fCHO (20.1 % CP/18.0 % TDF) diets. After 21-23 d, samples of proximal and distal colonic mucosae were investigated in Ussing chambers with respect to the paracellular and transcytotic passages of macromolecules and epithelial ion transport. The high-fCHO diets were found to reduce the permeability of the distal colon to the transcytotic marker horseradish peroxidase (HRP, 44 kDa; P <0.05) and also reduce the paracellular permeation of N-hydroxysuccinimide-biotin into the submucosa (443 Da; P <0.05), whereas that of HRP was decreased by the high-fCP diets (P <0.01). Short-circuit current (active ion transport), transepithelial resistance (barrier function) and charge selectivity were largely unaffected in both the segments. However, the high-fCP diets were found to suppress the aldosterone-induced epithelial Na channel activity (P <0.01) irrespective of fCHO inclusion. The high-fCP diets generally reduced the expression of colonic claudin-1, claudin-2 and claudin-3 (P <0.01), while that of claudin-4 was increased by the high-fCHO diets (P <0.01). The high-fCHO diets also altered the ratio between occludin forms (P <0.05) and increased the expression of tricellulin in the proximal colon, which was not observed with high-fCP diets. In conclusion, dietary fCHO and fCP exerted few and largely independent effects on functional measurements, but altered tight junction protein composition in a compensatory way, so that colonic transport and barrier properties were only marginally affected. PMID- 24229736 TI - Generalized pure cutaneous Rosai-Dorfman disease: a link between inflammation and cancer not associated with mitochondrial DNA and SLC29A3 gene mutation? AB - Recently, we described a case of generalized pure cutaneous Rosai-Dorfman disease in a 43-year-old Asian man in JAMA. The lesions distributed on nearly all of the skin of the whole body, except for mucous sites. Molecular, immunophenotypic, and sequencing analyses seem to define it as a histiocytic-mesenchymal transition and intermediate proliferative histiocytosis not associated with mtDNA large deletion and pathogenic mutation, as well as the SLC29A3 gene mutation. PMID- 24229737 TI - A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection. AB - Dietary lipids are transported via lymph to the liver and transformed to lipoproteins which bind to members of the low density lipoprotein receptor family (LDL-RFMs). Certain LDL-RFMs, e.g., very low density lipoprotein receptor (VLDLR), are also bound by inactivated proteinase inhibitors, the most abundant being alpha1proteinase inhibitor (alpha1PI, alpha1antitrypsin). Inflammation/infection, including HIV-1 infection, is accompanied by low levels of CD4+ T cells and active alpha1PI and high levels of inactivated alpha1PI. By inducing LDL-RFMs-mediated cellular locomotion, active alpha1PI regulates the number of CD4+ T cells. We sought to investigate whether CD4+ T cells and alpha1PI directly impact lipoprotein levels. At the cellular level, we show that active alpha1PI is required for VLDLR-mediated uptake of receptor-associated cargo, specifically CD4-bound HIV-1. We show that active alpha1PI levels linearly correlate with LDL levels in HIV-1 infected individuals (P<0.001) and that therapeutic, weekly infusions of active alpha1PI elevate the number of CD4+ T cells and HDL levels while lowering LDL levels in patients on antiretroviral therapy with controlled HIV-1. Based on the unusual combination of lipodystrophy and low levels of alpha1PI and CD4+ T cells in HIV-1 disease, we reveal that LDL and alpha1PI participate in a feedback regulatory pathway. We demonstrate integral roles for sequentially acting active and inactive alpha1PI in the uptake and recycling of receptors and cargo aggregated with VLDLR including CD4 and chemokine receptors. Evidence supports a role for alpha1PI as a primary sentinel to deploy the immune system as a consequence of its role in lipoprotein transport. PMID- 24229738 TI - A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. AB - OBJECTIVE: A prospective double-blind randomized control trial (RCT) to evaluate the benefit of a combinatorial, five gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used in the treatment of major depression in an outpatient psychiatric practice. METHODS: Depressed adult outpatients were randomized to a treatment as usual (TAU, n=25) arm or a pharmacogenomic-informed GeneSight (n=26) arm. Subjects were blinded to their treatment group and depression severity was assessed by blinded study raters. Within two days of enrollment, clinicians of subjects in the guided group received the GeneSight report that categorized each of 26 psychotropic medications within a green, yellow, or red "bin" based on the relationship of each medication to a subject's pharmacokinetic and pharmacodynamic combinatorial gene variant profile. Antidepressant medication changes began within 2 weeks after baseline assessments. Depression severity was assessed by blinded study raters using the HAMD-17, PHQ-9, QIDS-SR, and QIDS-CR administered 4, 6, and 10 weeks after baseline assessment. RESULTS: Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08). CONCLUSIONS: Pharmaco-genomic-guided treatment with GeneSight doubles the likelihood of response in all patients with treatment resistant depression and identifies 30% of patients with severe gene drug interactions who have the greatest improvement in depressive symptoms when switched to genetically suitable medication regimens. PMID- 24229739 TI - Mechanisms and efficacy of vismodegib in the treatment of basal cell carcinoma. AB - Historically patients with advanced basal cell carcinoma have been subjected to large surgical resections for the treatment of their disease. However, with the development of vismodegib, a first in class molecule that acts to inhibit the hedgehog pathway, patients with advanced and metastatic basal cell carcinoma may have renewed hope in limiting the morbidity involved with surgery. Preliminary data shows a relatively good safety profile and promising results, although further research remains to be conducted. Current progress on utilization of vismodegib for the treatment of advanced basal cell carcinoma is reviewed in this article. Only literature with objective clinical evidence was included in this review. PMID- 24229740 TI - Orphan drug development in muscular dystrophy: update on two large clinical trials of dystrophin rescue therapies. AB - Duchenne muscular dystrophy is a relatively common 'rare disorder,' with an incidence of about 1/5,000 males worldwide. The responsible gene and deficient protein (dystrophin) were identified in 1987, an early success of human molecular genetics and emerging genome projects. A rational approach to therapeutics is to replace dystrophin in patient muscle, thus addressing the primary biochemical defect. Fast forward 25 years, and two phase 2b/3 trials have been carried out with agents designed to induce de novo dystrophin production in DMD patient's muscle; ataluren (stop codon read through) with 174 patients, and drisapersen (exon skipping) with 186 patients. Both used a six minute walk test as the primary outcome measure. Neither drisapersen nor high dose ataluren showed any significant improvement in this outcome, whereas low dose ataluren is reported to show some possible improvement. Experience with ataluren and drisapersen has been disappointing and this is a good time to ask: What can we learn from these programs and how can this inform further drug development in DMD? At the times these two trials were started, there was a lack of existing data and infrastructure regarding both clinical and biochemical outcome measures. The recent publications of more extensive natural history data in multiple DMD cohorts, and ongoing efforts to define reliable and sensitive dystrophin assays are important. If the drisapersen and ataluren programs were instead begun today, new progress in biochemical and clinical endpoints may have triggered a re design, with better de-risking in phase 2 studies prior to resource-intensive phase 3 trials. PMID- 24229741 TI - Integration of genomics into medical practice. AB - Although some have wondered whether the sequencing of the human genome has led to major advances in medicine, in fact there are multiple examples where genomics has been integrated into medical practice. In the area of prevention, genomic approaches are now used for non-invasive prenatal testing of fetal DNA in the maternal circulation, for expanded preconceptional screening for carrier status, for autosomal recessive disorders, and for assessment of risk of common disease. In the area of diagnosis, major advances have been made in cytogenomics and in use of whole exome or whole genome sequencing. In therapeutics, pharmacogenetic testing is now feasible, tumor genome sequencing is being used to guide cancer therapy, and genomic discoveries are enabling development of new targeted therapies. Ultimately it is possible that genome sequencing may be done for all individuals on a routine basis, though there remain significant technical, ethical, and medical systems challenges to be overcome. It is likely that integration of genomics into medical practice will occur gradually over a long period of time, but the process is now well underway. PMID- 24229742 TI - Morphological changes and germ layer formation in the porcine embryos from days 7 13 of development. AB - Morphogenesis and identification of embryonic differentiation in porcine embryos are crucial issues for developmental biology and laboratory animal science. The current paper presents a study on the asynchronous development of hatched porcine embryos from days 7 to 13 post-insemination. Examination of semi-thin sections of the hypoblast showed that it had characteristics similar to those of the mouse anterior visceral endoderm during embryonic disc formation. Also, a cavity appeared in the epiblast, which was similar to a mouse proamniotic cavity. With the gradual disappearance of Rauber's layer, the cavity opened and contacted the external environment directly, all of which formed the embryonic disc. To confirm the differentiation characteristics, we performed immunohistochemical analyses and showed that GATA6 was detected clearly in parietal endoderm cells during embryonic disc establishment. OCT4 was expressed in the inner cell mass (ICM) and trophoblast of hatched blastocysts and in the epiblast during formation of the embryonic disc. However, OCT4 showed comparatively decreased expression in the posterior embryonic disc, primitive streak and migrating cells. SOX2 was present in the ICM and epiblast. Therefore, both SOX2 and OCT4 can be used as markers of pluripotent cells in the porcine embryonic disc. At the start of gastrulation, staining revealed VIMENTIN in the posterior of the embryonic disc, primitive streak and in migrating cells that underlay the embryonic disc and was also expressed in epiblast cells located in the anterior primitive streak. Together with serial sections of embryos stained by whole mount immunohistochemistry, the mesoderm differentiation pattern was shown as an ingression movement that took place at the posterior of the embryonic disc and with bilateral migration along the embryonic disc borders. PMID- 24229743 TI - Outbreak of gastroenteritis caused by norovirus GII.4 Sydney variant after a wedding reception at a resort/activity centre, Finland, August 2012. AB - In August 2012, an outbreak of gastroenteritis occurred among 88 persons attending a wedding reception at a resort/activity centre in Ylojarvi, Finland. Of 39 interviewed guests, 23 met the case definition. Two persons were hospitalized. Epidemiological, laboratory and environmental investigations were conducted to characterize the outbreak and to recommend control measures. Investigation confirmed the presence of a new strain of norovirus GII.4 Sydney variant in stool specimens obtained from two wedding guests and on several environmental surfaces in the centre. In the questionnaire study, none of the foods or beverages served during the reception were significantly associated with the illness. Additional cases of gastroenteritis that occurred at the centre before and after the wedding reception supported the hypothesis of environmental transmission of norovirus. After thorough cleansing and disinfection and 1 week's quarantine, no new cases with symptoms typical for norovirus infection were identified at the centre. PMID- 24229744 TI - Effects of supplemental zinc amino acid complex on gut integrity in heat-stressed growing pigs. AB - Heat stress (HS) jeopardizes livestock health and productivity and both may in part be mediated by reduced intestinal integrity. Dietary zinc improves a variety of bowel diseases, which are characterized by increased intestinal permeability. Study objectives were to evaluate the effects of supplemental zinc amino acid complex (ZnAA) on intestinal integrity in heat-stressed growing pigs. Crossbred gilts (43+/-6 kg BW) were ad libitum fed one of three diets: (1) control (ZnC; 120 ppm Zn as ZnSO4; n=13), (2) control+100 ppm Zn as ZnAA (Zn220; containing a total of 220 ppm Zn; n=14), and (3) control+200 ppm Zn as ZnAA (Zn320; containing a total of 320 ppm Zn; n=16). After 25 days on their respective diets, all pigs were exposed to constant HS conditions (36 degrees C, ~50% humidity) for either 1 or 7 days. At the end of the environmental exposure, pigs were euthanized and blood and intestinal tissues were harvested immediately after sacrifice. As expected, HS increased rectal temperature (P?0.01; 40.23 degrees C v. 38.93 degrees C) and respiratory rate (P?0.01; 113 v. 36 bpm). Pigs receiving ZnAA tended to have increased rectal temperature (P=0.07; +0.27 degrees C) compared with ZnC-fed pigs. HS markedly reduced feed intake (FI; P?0.01; 59%) and caused BW loss (2.10 kg), but neither variable was affected by dietary treatment. Fresh intestinal segments were assessed ex vivo for intestinal integrity. As HS progressed from days 1 to 7, both ileal and colonic transepithelial electrical resistance (TER) decreased (P?0.05; 34% and 22%, respectively). This was mirrored by an increase in ileal and colonic permeability to the macromolecule dextran (P?0.01; 13- and 56-fold, respectively), and increased colonic lipopolysaccharide permeability (P?0.05; threefold) with time. There was a quadratic response (P?0.05) to increasing ZnAA on ileal TER, as it was improved (P?0.05; 56%) in Zn220-fed pigs compared with ZnC. This study demonstrates that HS progressively compromises the intestinal barrier and supplementing ZnAA at the appropriate dose can improve aspects of small intestinal integrity during severe HS. PMID- 24229745 TI - Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. AB - OBJECTIVE: Recent, large, randomized controlled trials (RCTs) showed no benefit of long-acting injectable (LAI) antipsychotics over oral antipsychotics in preventing relapse in schizophrenia, nor did a recent meta-analysis incorporating these studies. However, RCTs might enroll a disproportionate number of patients with better treatment adherence and lower illness severity. Mirror-image studies, which compare periods of oral antipsychotic versus LAI treatment in the same patients, might therefore better reflect the real-world impact of LAIs. DATA SOURCES: A systematic literature search without language restriction was conducted using MEDLINE/PubMed, Cochrane Library, Web of Science, PsycINFO, and CINAHL until May 31, 2012. Search terms included synonyms of (1) antipsychotic(s) AND (2) schizophrenia and related disorders AND (3) depot, (long-acting) injection(s), microsphere, decanoate, palmitate, enanthate. STUDY SELECTION: Of 5,483 identified citations, 607 articles were fully inspected, and 582 were ineligible. Finally, 25 mirror-image studies from 28 countries that followed 5,940 patients with schizophrenia for >= 12 months (>= 6 months each on oral antipsychotic and LAI treatment) met the inclusion criteria and were analyzed. DATA EXTRACTION: Coprimary outcomes were hospitalization risk and number of hospitalizations. Secondary outcomes included hospitalization days and length of stay. DATA SYNTHESIS: LAIs showed strong superiority over oral antipsychotics in preventing hospitalization (16 studies, N = 4,066; risk ratio = 0.43; 95% CI, 0.35-0.53; P < .001) and in decreasing the number of hospitalizations (15 studies, 6,342 person-years; rate ratio = 0.38; 95% CI, 0.28-0.51; P < .001). This strong advantage was also observed for secondary outcomes and in multiple clinically relevant subpopulations and treatment groups. CONCLUSIONS: Results from mirror-image studies in patients eligible for clinical use of LAIs showed strong superiority of LAIs compared to oral antipsychotics in preventing hospitalization. The results were in contrast to the recent meta-analysis of RCTs, which showed no superiority of LAIs. Given the possible biases in mirror image studies, such as expectation bias, natural illness course, and time effect, a cautious interpretation is required. Nevertheless, the population in mirror image studies better reflects the population receiving LAIs in clinical practice. PMID- 24229747 TI - Preventing domestic violence in families of veterans. PMID- 24229746 TI - Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: Intravenous N-methyl-d-aspartate (NMDA) antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial of the NMDA antagonist memantine as an augmentation treatment for patients with DSM IV major depressive disorder. METHOD: Adult outpatients with major depressive disorder and partial response or nonresponse to their current antidepressant (as indicated by a 17-item Hamilton Depression Rating Scale score of >= 16 at baseline) were randomized (from July 2006-December 2011) to add memantine (flexible dose 5-20 mg/d, with all memantine group participants reaching the dose of 20 mg/d) (n = 15) or placebo (n = 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated-measures mixed effects models using last-observation carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects. RESULTS: 84% of participants completed the trial, including 93% of participants receiving memantine. Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (beta = 0.133, favoring placebo, P = .74) or at study completion (week 8 mean [SD] MADRS score change = -7.13 [6.61] [memantine]; -7.25 [11.14] [placebo]; P = .97). A minimal to small effect size (comparing change to baseline variability) favoring placebo was observed (Cohen d = 0.19). Similarly, no substantial effect sizes favoring memantine nor statistically significant between-group differences were observed on secondary efficacy outcomes. CONCLUSIONS: This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment for major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00344682. PMID- 24229748 TI - Lyme neuroborreliosis presenting with alexithymia and suicide attempts. PMID- 24229750 TI - Childhood trauma is associated with severe clinical characteristics of bipolar disorders. AB - OBJECTIVE: Beyond genetic risk variants, the pathophysiology of bipolar disorders is likely to be partly determined by environmental susceptibility factors. Our study is one of the first to investigate, in a large sample of well-characterized bipolar patients, associations between clinical presentations and childhood trauma subtypes, including neglect and abuse items. METHOD: 587 patients with DSM IV-defined bipolar disorder were recruited from France and Norway between 1996 2008 and 2007-2012, respectively. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Clinical variables were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (Norwegian sample) or the Diagnostic Interview for Genetic Studies (French sample). RESULTS: Earlier age at onset of bipolar illness, suicide attempts, rapid cycling, and an increased number of depressive episodes each had significant associations (P <= .001) with at least 1 subtype of childhood trauma (emotional abuse, sexual abuse, and emotional neglect). Multivariate analyses investigating trauma variables together showed that both emotional and sexual abuse were independent predictors of lower age at onset (P = .002 for each) and history of suicide attempts (OR = 1.60 [95% CI, 1.07 to 2.39], P = .023; OR = 1.80 [95% CI, 1.14 to 2.86], P = .012, respectively), while sexual abuse was the strongest predictor of rapid cycling (OR = 2.04 [95% CI, 1.21 to 3.42], P = .007). Females reported overall higher childhood trauma frequency and greater associations to clinical expressions than males (P values < .05). CONCLUSIONS: Our results demonstrate consistent associations between childhood trauma and more severe clinical characteristics in bipolar disorder. Further, they show the importance of including emotional abuse as well as the more frequently investigated sexual abuse when targeting clinical characteristics of bipolar disorder. PMID- 24229749 TI - Treating nicotine dependence by targeting attention-deficit/ hyperactivity disorder (ADHD) with OROS methylphenidate: the role of baseline ADHD severity and treatment response. AB - OBJECTIVE: To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. METHOD: This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD RS) score, change in ADHD-RS score during treatment, and their interactions. RESULTS: Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score >= 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (<= 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). CONCLUSIONS: OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00253747. PMID- 24229751 TI - The pervasive and persistent neurobiological and clinical aftermath of child abuse and neglect. PMID- 24229752 TI - Depression in women: new findings. PMID- 24229754 TI - Efficacy and safety of desvenlafaxine 50 mg/d in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder. AB - OBJECTIVE: Evaluate the 8-week efficacy and safety of desvenlafaxine at the recommended dose of 50 mg/d in perimenopausal and postmenopausal women with major depressive disorder (MDD) based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. METHOD: This phase 4, multicenter, parallel-group, randomized, double-blind, placebo-controlled study was conducted from June 30, 2010, to June 8, 2011. Patients received placebo or desvenlafaxine 50 mg/d (1:1 ratio; n = 217 in each group). The primary outcome measure was the change at week 8 in the 17-item Hamilton Depression Rating Scale (HDRS17) total score. Secondary outcome measures included change in the Sheehan Disability Scale (SDS), the Clinical Global Impressions-Improvement scale (CGI I), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Visual Analog Scale-Pain Intensity (VAS-PI). RESULTS: At end point, compared to placebo, desvenlafaxine was associated with a significantly greater decrease in HDRS17 total scores (last-observation-carried-forward analysis; adjusted mean change from baseline -9.9 vs -8.1, respectively; P = .004) and significant improvements on the CGI-I (P < .001), MADRS (P = .002), SDS (P = .038), and VAS-PI (P < .001). Improvements on the SDS and VAS-PI reached significance by week 2. Desvenlafaxine was generally safe and well tolerated. CONCLUSIONS: Short-term treatment with desvenlafaxine 50 mg/d was effective for the treatment of MDD in perimenopausal and postmenopausal women, with significant benefits on pain and functional outcomes evident as early as week 2. The safety and tolerability of desvenlafaxine were consistent with data in other populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01121484. PMID- 24229755 TI - Female reproductive life cycle and hormones: methodology to improve clinical trials. PMID- 24229753 TI - A gender analysis of the study of pharmacotherapy of psychotic depression (STOP PD): gender and age as predictors of response and treatment-associated changes in body mass index and metabolic measures. AB - BACKGROUND: Gender differences exist in psychiatric disorders; however, gender has not been well studied in psychotic depression. This analysis of the largest clinical trial in psychotic depression examined the effects of age and gender on clinical characteristics and predictors of treatment outcome and treatment associated changes in body mass index (BMI) and metabolic measures. METHOD: Secondary analyses were performed on data from 259 subjects with major depressive disorder with psychotic features (DSM-IV-TR) aged 18-93 years in the double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression (Study of Pharmacotherapy of Psychotic Depression). Sociodemographic factors, clinical characteristics, treatment outcome, and treatment-associated changes in BMI and metabolic measures were analyzed by gender and age. Subjects were enrolled from December 2002 to June 2007. RESULTS: Female gender was associated with divorced (chi(2)(1) = 5.3, P = .03) or widowed (chi(2)(1) = 8.1, P <= .01) marital status. Comorbid anxiety disorders were more common in women than in men (chi(2)(1) = 4.9, P = .03). Hallucinations (chi(2)(1) = 7.8, P = .005) and delusions with disorganization (t(257) = -2.10, P = .04) were significantly associated with female gender, as were higher cholesterol measures (chi(2)(1) = 7.15, P = .008). There were no significant interactions between treatment and gender in terms of change in BMI. Gender was not associated with treatment response. DISCUSSION: This study is the first analysis of gender and age as predictors of treatment outcome and treatment associated changes in BMI and metabolic adverse effects in psychotic depression. Gender differences exist in patients with psychotic depression, most notably with regard to the presence of hallucinations. Female gender was associated with metabolic measures. Future studies with larger sample sizes may detect small gender differences in treatment outcome and treatment-associated changes in BMI and metabolic measures in psychotic depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00056472. PMID- 24229756 TI - Decision making and antipsychotic medication treatment for youth with autism spectrum disorders: applying guidelines in the real world. PMID- 24229757 TI - Phenoconversion of cytochrome P450 2D6: the need for identifying the intermediate metabolizer genotype. PMID- 24229758 TI - Dr Preskorn replies. PMID- 24229759 TI - Borderline personality disorder symptoms and treatment seeking over the past 12 months: an investigation using the national comorbidity survey-replication (NCS R). PMID- 24229760 TI - Mental health needs of returning veterans. AB - As more service members return from war zones around the world, clinicians must be prepared to treat them. Veterans with PTSD and other mental disorders must overcome the stigma associated with seeking treatment, and clinicians must equip these patients and their family members to deal with challenging symptoms. Clinicians should learn about military culture and jargon to better understand these patients and should become familiar with veteran resources to direct veterans and their families to the appropriate services. Clinicians may also need to communicate with their patients' employers to help both parties deal with illnesses such as PTSD. A coordinated effort is needed to meet the needs of veterans and their families, and clinicians play an integral role in recognizing and meeting those needs. PMID- 24229761 TI - Monitoring treatment and managing adherence in schizophrenia. AB - The majority of patients with schizophrenia will be nonadherent at some point during their treatment, which is why clinicians must assess adherence at each visit and promptly address any barriers. Treatment adherence can be negatively impacted by substance use, cognitive impairment, complex treatment regimens, and antipsychotic-induced adverse effects. Clinicians must monitor these risk factors, particularly metabolic, neurologic, and other side effects, not only to improve adherence but also to protect patients from dangerous health conditions. Interventions that can address some barriers to treatment adherence include adjusting medications as necessary, implementing lifestyle changes, using long acting injectable antipsychotics, educating patients and their families, and implementing psychosocial therapy. With the appropriate interventions and support, patients with schizophrenia can maintain their treatment regimens and avoid relapse. PMID- 24229762 TI - Learning from history: how to swallow a pill. PMID- 24229763 TI - Antecedent trauma exposure and risk of depression in the perinatal period. AB - OBJECTIVE: To assess the impact of antecedent trauma on the risk of antenatal and postpartum depression in a prospective, longitudinal cohort of pregnant women. METHOD: 374 participants (pregnant women aged 20-34 years) were recruited from a hospital-based obstetrics practice serving a predominantly low-income, inner-city population between May 2007 and May 2012. Clinical diagnostic interviews and psychosocial questionnaires were administered at 18 and 32 weeks of gestation and at 6 weeks and 6 months postpartum. Lifetime exposure to and details of traumatic events were recorded. Depression during pregnancy or the postpartum period was diagnosed according to DSM-IV-TR. RESULTS: 39% of the sample reported at least 1 traumatic event; trauma history (odds ratio [OR] = 2.16; 95% CI, 1.31-3.54) and, particularly, experiencing childhood sexual abuse (OR = 2.47; 95% CI, 1.27-4.78), someone close experiencing violence (OR = 2.19; 95% CI, 1.11-4.32), and the unexpected death or illness of someone close (OR = 2.15; 95% CI, 1.14-4.05) predicted antenatal but not postpartum depression. A clear dose-response effect of trauma on antenatal depression was observed; women who experienced 3 or more traumas had a 4-fold risk (OR = 4.34; 95% CI, 2.16-8.70) of antenatal depression compared to women with no trauma history. CONCLUSIONS: Antecedent trauma significantly increases the risk of antenatal depression, but antenatal depression alone does not appear to predict postpartum depression. Routine screening for trauma exposure and depression is warranted during pregnancy to aid in the early detection and treatment of depression. Future studies need to examine mechanisms that may trigger affective episodes in trauma-exposed women, who may be especially vulnerable to depressive episodes during pregnancy. PMID- 24229764 TI - Recent advances in the diagnosis, impact on production and prediction of Fasciola hepatica in cattle. AB - Fasciola hepatica is a pathogenic trematode parasite of ruminants with a global distribution. Here, we briefly review the current epidemiology of bovine fasciolosis in Europe and discuss the progress made over the last decade in the diagnosis, impact on production and prediction of F. hepatica in cattle. Advances in diagnosis have led to significantly improved coprological and serological methods to detect presence of infection. Diagnostic test results have been correlated with intensity of infection and associated production losses, unravelling the impact on carcass weight and milk yield in modern cattle production systems. The economic impact of fasciolosis may, however, go beyond the direct impacts on production as evidence shows that F. hepatica can modulate the immune response to some co-infections. Control of bovine fasciolosis remains hampered by the limitations of the currently available flukicidal drugs: few drugs are available to treat dairy cows, many have low efficacies against juvenile stages of F. hepatica and there is evidence for the development of drug resistance. This makes research into the prediction of risk periods, and thus the optimum application of available drugs more pertinent. In this field, the recent research focus has been on understanding spatial risk and delivering region specific spatial distribution maps. Further advances in epidemiological and economic research on bovine fasciolosis are expected to deliver farm-specific economic assessments of disease impact, to leverage non-chemotherapeutic management options and to enhance a more targeted use of anthelmintics. PMID- 24229765 TI - How do the features of mindfulness-based cognitive therapy contribute to positive therapeutic change? A meta-synthesis of qualitative studies. AB - BACKGROUND: The exploration of Mindfulness-based Cognitive Therapy through qualitative investigation is a growing area of interest within current literature, providing valuable understanding of the process of change experienced by those engaging in this therapeutic approach. AIMS: This meta-synthesis aims to gain a deeper understanding of how the features of Mindfulness-based Cognitive Therapy contribute to positive therapeutic change. METHOD: Noblit and Hare's (1988) 7-step meta-ethnography method was conducted in order to synthesize the findings of seven qualitative studies. RESULTS: The process of reciprocal translation identified the following five major themes: i) Taking control through understanding, awareness and acceptance; ii) The impact of the group; (iii) Taking skills into everyday life; (iv) Feelings towards the self; (v) The role of expectations. CONCLUSION: The synthesis of translation identified the higher order concept of "The Mindfulness-based Cognitive Therapy Journey to Change", which depicts the complex interaction between the five themes in relation to how they contribute to positive therapeutic change. The findings are discussed in relation to previous research, theory and their implications for clinical practice. PMID- 24229766 TI - Developmental potential and kinetics of pig embryos with different cytoplasmic volume. AB - The effects of cytoplasmic volumes on development and developmental kinetics of in vitro produced porcine embryos were investigated. During hand-made cloning (HMC), selected cytoplasts were separated into two groups according to their size in relation to the initial oocyte: ~75% or ~50%. Following two fusion steps and activation (day 0), reconstructed embryos were cultured in vitro for 6 days. Cleavage rates on day 2 as well as blastocyst rates and cell numbers on day 6 were recorded. Results showed that embryo development was no different for ~50% versus ~75% cytoplasm at first fusion. This result was used in the following experiments, where the effect of varying cytoplasm volume in second fusion to obtain a final cytoplasm volume of ~75% to ~200% was tested. The results showed that the lowest quality was obtained when the final cytoplasm volume was ~75% and the highest quality at ~200% of the original oocyte. Similar results were observed in parthenogenetic (PA) embryos activated with different cytoplasmic volumes. A common pattern for the developmental kinetics of HMC and PA embryos was observed: the smaller group tended to have a longer time for the first two cell cycles, but subsequently a shorter time to form morula and blastocyst. In conclusion, the developmental kinetics of in vitro produced embryos was affected by the cytoplasm volume of the initial oocyte, and this further accounted for the developmental ability of the reconstructed embryos. PMID- 24229767 TI - Conductive channels identified with contrast-enhanced MR imaging predict ventricular tachycardia in systolic heart failure. AB - OBJECTIVES: This study evaluated whether the conductive channel (CC) identified by late gadolinium enhanced-cardiac magnetic resonance (LGE-CMR) is associated with ventricular tachycardia (VT) in patients with systolic heart failure (HF). BACKGROUND: One recent study demonstrated that the CC formed by heterogeneous tissue within the core scar could be detected by LGE-CMR and that the CC is responsible for clinical VT. We hypothesized that the CC could help identify HF patients at risk for VT. METHODS: A total of 63 patients from a CMR database with left ventricular ejection fraction (LVEF) below 50% and with hyperenhancement on LGE-CMR were included. The cine and LGE images were analyzed to derive the LV function and scar characteristics, and to identify the CC. The outcomes, including VT, ventricular fibrillation (VF), and total mortality, were obtained by reviewing medical records. RESULTS: After a median 1,379 (interquartile range: 271 to 1,896) days of follow-up, 8 patients had VT/VF attacks and 14 patients died. Among the CMR-measured parameters, only the probability of identifying the CC by LGE-CMR was higher in patients with VT/VF than those without VT/VF (75.0% vs. 16.4%, p < 0.001). The probability of identifying the CC was also higher in the total mortality group than the survival group (50.0% vs. 16.3%, p = 0.004). The other LGE-CMR variables were not significantly different between the 2 groups. A univariate Cox regression model showed that CC identification was positively associated with VT/VF attacks (hazard ratio [HR]: 27.032, 95% confidence interval [CI]: 3.291 to 222.054, p = 0.002) and excess total mortality (HR: 4.766, 95% CI: 1.643 to 13.824, p = 0.004). The LVEF was inversely associated with VT/VF attacks (HR: 0.119, 95% CI: 0.015 to 0.977, p = 0.048) and excess total mortality (HR: 0.491, 95% CI: 0.261 to 0.925, p = 0.028) during follow-up. CONCLUSIONS: We demonstrated that CC identification using LGE-CMR can help identify HF patients at risk for VT/VF. PMID- 24229768 TI - Relationship between carotid disease on ultrasound and coronary disease on CT angiography. AB - OBJECTIVES: The purpose of this study was to assess the relationship between carotid artery disease by ultrasound and coronary artery disease by coronary computed tomography angiography (CTA) and to identify carotid ultrasound parameters predictive of coronary artery disease. BACKGROUND: Carotid ultrasound and CTA are noninvasive modalities used to image atherosclerosis. Studies examining the relationship between the 2 tests, however, are lacking. METHODS: We performed carotid ultrasound on predominantly nondiabetic subjects referred for CTA. Carotid intima media thickness (IMT) and plaque were assessed and compared with coronary artery calcification and the number of coronary arteries with any evidence of atherosclerosis on CTA. RESULTS: A total of 150 subjects underwent both CTA and carotid ultrasound on the same day. Carotid plaque was present in 71.3% (n = 107), whereas the presence of at least 1 coronary artery with disease on CTA was present in 57.1% (n = 84). Carotid plaque was present in 47.6% (30 of 63) of subjects with a calcium score of 0 and 88.5% (77 of 87) of subjects with a calcium score >0 (p = 0.0001). Similarly carotid plaque was present in 52.4% (33 of 63) of subjects with no CTA evidence of atherosclerosis versus 85.7% (72 of 84) of subjects with any CTA evidence of atherosclerosis (p < 0.0001). Carotid plaque, IMT >= 1.5 mm, or averaged mean IMT >0.75 mm were associated with a calcium score >0 (odds ratio: 5.4, p < 0.0001, 2.7, p < 0.001; 2.9, p = 0.011, respectively) and disease in at least 1 vessel on CTA (odds ratio: 2.8, p = 0.03, 2.19, p = 0.073; 2.22, p = 0.058, respectively) independent of age and sex. CONCLUSIONS: Carotid plaque and increased carotid IMT are associated with the presence and severity of coronary calcification and disease on CTA in ambulatory subjects. PMID- 24229769 TI - Can carotid plaque predict coronary plaque? PMID- 24229770 TI - Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging. AB - OBJECTIVES: The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. BACKGROUND: Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. METHODS: Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to background ratio. RESULTS: Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 +/- 8.3 years; glycosylated hemoglobin: 6.72 +/- 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group ( 0.12 +/- 0.06 vs. 0.09 +/- 0.07, p = 0.032), as well as changes in high sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). CONCLUSIONS: Our study indicated that pioglitazone attenuated left main trunk inflammation in patients with impaired glucose tolerance or DM in a glucose-lowering independent manner, suggesting that pioglitazone may protect against cardiac events in patients with impaired glucose tolerance or DM by suppressing coronary inflammation. (Anti-Inflammatory Effects of Pioglitazone; NCT00722631). PMID- 24229771 TI - Predictors for functionally significant in-stent restenosis: an integrated analysis using coronary angiography, IVUS, and myocardial perfusion imaging. AB - OBJECTIVES: The aim of this study was to assess the clinical and morphological predictors for functionally significant in-stent restenosis (ISR). BACKGROUND: Although they have been studied de novo in native coronary artery lesions, the relationships between clinical and morphological characteristics and the hemodynamic significance of ISR are not well understood. METHODS: In 175 patients with ISR of a single coronary artery (angiographic stenosis >50%), we compared quantitative coronary angiography and intravascular ultrasound (IVUS) with stress myocardial single-photon emission computed tomography (SPECT). A positive SPECT was a reversible perfusion defect in the territory of the ISR artery. RESULTS: Overall, 103 (59%) patients had a positive SPECT. In-segment IVUS minimal lumen area (MLA) was significantly smaller in lesions with positive SPECT compared with negative SPECT (1.7 +/- 0.5 mm(2) vs. 2.4 +/- 0.8 mm(2), p < 0.001). Stent underexpansion (minimal stent area <5.0 mm(2)) was more common in the positive SPECT group than in the negative SPECT group (52% vs. 32%, p = 0.010). A positive SPECT was seen in 54% (65 of 121) of focal ISR lesions compared with 70% (38 of 54) of multifocal or diffuse ISR lesions as assessed by IVUS (p = 0.039). Independent determinants for a positive SPECT were diabetes (odds ratio [OR]: 2.41; 95% confidence interval [CI]: 1.02 to 5.68; p = 0.046), in-segment angiographic diameter stenosis (OR: 1.06; 95% CI: 1.03 to 1.09; p < 0.001), in segment IVUS-MLA (OR: 0.30; 95% CI: 0.14 to 0.63; p = 0.001), stent underexpansion (minimal stent area <5.0 mm(2)), (OR: 2.91; 95% CI: 1.19 to 7.07; p = 0.019), proximal location of the IVUS-MLA (OR: 4.62; 95% CI: 1.75 to 12.18; p = 0.002), and a multifocal or diffuse ISR pattern (OR: 2.50; 95% CI: 0.99 to 6.28; p = 0.050). An in-segment angiographic diameter stenosis >=69.5% (72% sensitivity, 74% specificity, area under the curve = 0.793) and an IVUS-MLA <=1.9 mm(2) (67% sensitivity, 75% specificity, area under the curve = 0.756) best predicted a positive SPECT; however, the overall diagnostic accuracies were only 73% and 70%, respectively. CONCLUSIONS: In lesions with ISR, neither angiography nor IVUS accurately predicted an abnormal SPECT. PMID- 24229772 TI - Management of mitral stenosis using 2D and 3D echo-Doppler imaging. AB - Although the prevalence of rheumatic fever is decreasing in developed countries, it still affects numerous areas in the nonindustrialized world. Untreated mitral stenosis (MS) contributes to a significant global morbidity and mortality. Echocardiography is the main diagnostic imaging modality with which to evaluate mitral valve (MV) obstruction and assess the severity and hemodynamic consequences of MS as well as valve morphology. According to current guidelines and recommendations for clinical practice, the severity of MS should not be defined by a single value but assessed by valve areas, mean Doppler gradients, and pulmonary pressures. Transthoracic echocardiography is usually sufficient to grade MS severity and to define the morphology of the valve. Transesophageal echocardiography is used when the valve cannot be adequately assessed with transthoracic echocardiography and to exclude intracardiac thrombi before a percutaneous or surgical intervention. Three-dimensional transthoracic and transesophageal echocardiographic assessment provide more detailed physiological and morphological information. Current definitive treatment for severe MS involves percutaneous mitral balloon valvuloplasty (PMBV) or surgery. The effectiveness of PMBV is related to the etiology of MS, and certain anatomic characteristics tend to predict a more successful outcome for PMBV, whereas other MV structural findings might suggest balloon valvuloplasty to be less likely successful or even contraindicated. PMID- 24229773 TI - Intelligent platforms for disease assessment: novel approaches in functional echocardiography. AB - Accelerating trends in the dynamic digital era (from 2004 onward) has resulted in the emergence of novel parametric imaging tools that allow easy and accurate extraction of quantitative information from cardiac images. This review principally attempts to heighten the awareness of newer emerging paradigms that may advance acquisition, visualization and interpretation of the large functional data sets obtained during cardiac ultrasound imaging. Incorporation of innovative cognitive software that allow advanced pattern recognition and disease forecasting will likely transform the human-machine interface and interpretation process to achieve a more efficient and effective work environment. Novel technologies for automation and big data analytics that are already active in other fields need to be rapidly adapted to the health care environment with new academic-industry collaborations to enrich and accelerate the delivery of newer decision making tools for enhancing patient care. PMID- 24229774 TI - Mitral paravalvular leak: description and assessment of a novel anatomical method of localization. PMID- 24229775 TI - Carotid artery OCT in cerebral infarction. PMID- 24229776 TI - Myocardial mechanics in noncontiguous HCM. PMID- 24229777 TI - De-novo thrombus formation and latent ligation failure following LAA exclusion. PMID- 24229778 TI - Vini, vidi, vici... restructured format for condensed abstracts. PMID- 24229779 TI - Are we up to speed?: from big data to rich insights in CV imaging for a hyperconnected world. PMID- 24229780 TI - CV imaging for fellows in training: challenges and opportunities. PMID- 24229781 TI - Gestational methyl donor deficiency alters key proteins involved in neurosteroidogenesis in the olfactory bulbs of newborn female rats and is associated with impaired olfactory performance. AB - Gestational methyl donor deficiency (MDD) leads to growth retardation as well as to cognitive and motor disorders in 21-d-old rat pups. These disorders are related to impaired neurogenesis in the cerebral neurogenic areas. Olfactory bulbs (OB), the main target of neuronal progenitors originating from the subventricular zone, play a critical role during the postnatal period by allowing the pups to identify maternal odour. We hypothesised that growth retardation could result from impaired suckling due to impaired olfactory discrimination through imbalanced apoptosis/neurogenesis in the OB. Since neurosteroidogenesis modulates neurogenesis in OB, in the present study, we investigated whether altered neurosteroidogenesis could explain some these effects. Pups born to dams fed a normal diet (n 24) and a MDD diet (n 27) were subjected to olfactory tests during the lactation and weaning periods (n 24 and 20, respectively). We studied the markers of apoptosis/neurogenesis and the expression levels of the key neurosteroidogenic enzyme aromatase, the cholesterol-transfer protein StAR (steroidogenic acute regulatory protein) and the ERalpha oestrogen receptor and the content of oestradiol in OB. The 21-d-old MDD female pups displayed lower body weight and impaired olfactory discrimination when compared with the control pups. MDD led to greater homocysteine accumulation and more pronounced apoptosis, along with impaired cell proliferation in the OB of female pups. The expression levels of aromatase, StAR and ERalpha as well as the content of oestradiol were lower in the OB of the MDD female pups than in those of the control female pups. In conclusion, gestational MDD may alter olfactory discrimination performances by affecting neurogenesis, apoptosis and neurosteroidogenesis in OB in a sex dependent manner. It may be involved in growth retardation through impaired suckling. PMID- 24229782 TI - Geo-Chip analysis reveals reduced functional diversity of the bacterial community at a dumping site for dredged Elbe sediment. AB - The dumping of dredged sediments represents a major stressor for coastal ecosystems. The impact on the ecosystem function is determined by its complexity not easy to assess. In the present study, we evaluated the potential of bacterial community analyses to act as ecological indicators in environmental monitoring programmes. We investigated the functional structure of bacterial communities, applying functional gene arrays (GeoChip4.2). The relationship between functional genes and environmental factors was analysed using distance-based multivariate multiple regression. Apparently, both the function and structure of the bacterial communities are impacted by dumping activities. The bacterial community at the dumping centre displayed a significant reduction of its entire functional diversity compared with that found at a reference site. DDX compounds separated bacterial communities of the dumping site from those of un-impacted sites. Thus, bacterial community analyses show great potential as ecological indicators in environmental monitoring. PMID- 24229783 TI - Human impact on a small barrier reef meadow of Posidonia oceanica (L.) Delile on the north Tyrrhenian coast (Italy). AB - The health status of an emerging Posidonia oceanica meadow, subject to high human impact, was studied. Biometric variables, heavy metals, PAHs and C, N, P contents were determined in sediment and seagrass samples. The meadow was found to grow under oligotrophic conditions and an increase in nutrient content was only recorded in autumn. In sediment, Hg exceeded its ERL (effects range low) and sometimes also its ERM (effects range medium), and Cu was close to its ERL. In leaves, Hg and Cu were relatively high but below their respective ERLs. Sediments close to the meadow were heavily contaminated with pyrolytic PAHs, some of which exceeded their ERLs. P. oceanica did not show major accumulation of PAHs, lighter molecules predominating. Despite 40 years of intense human activity, meadow growth dynamics and contaminant accumulation did not suggest that the meadow was regressing. PMID- 24229784 TI - Tolerance of Brazilian brain coral Mussismilia braziliensis to sediment and organic matter inputs. AB - In Brazil, where reefs occur in markedly turbid environments, the relationship between sedimentation/organic matter and corals is poorly known. Thus, the ex situ effects of sediment with and without organic matter over the DeltaF/Fm and physical state of Mussismilia braziliensis were analyzed. The DeltaF/Fm and coral physical state, evaluated through the susceptibility index to sedimentation (SI), were measured in seven colonies exposed to sedimentation (0-450 mg cm(-2) day( 1)) free of organic matter after 45 days of exposure, and in 12 colonies exposed to sedimentation (0-500 mg cm(-2) day(-1)) with organic matter content (10%), in which case DeltaF/Fm was measured after 72 h and SI after 120 h. In both cases there were effects of increasing sedimentation on the SI with no effect on DeltaF/Fm. Despite the tolerance to high sedimentation rates shown by this coral, we noted that the presence of organic matter might reduce its tolerance to sedimentation stress. PMID- 24229785 TI - Enhanced ex situ bioremediation of crude oil contaminated beach sand by supplementation with nutrients and rhamnolipids. AB - Mediterranean coastal regions are particularly exposed to oil pollution due to extensive industrialization, urbanization and transport of crude and refined oil to and from refineries. Bioremediation of contaminated beach sand through landfarming is both simple and cost-effective to implement compared to other treatment technologies. The purpose of the present study was to investigate the effect of alternative nutrients on biodegradation of crude oil contaminated beach sand in an effort to reduce the time required for bioremediation employing only indigenous hydrocarbon degraders. A natural sandy soil was collected from Agios Onoufrios beach (Chania, Greece) and was contaminated with weathered crude oil. The indigenous microbial population in the contaminated sand was tested alone (control treatment) or in combination with inorganic nutrients (KNO3 and K2HPO4) to investigate their effects on oil biodegradation rates. In addition, the ability of biosurfactants (rhamnolipids), in the presence of organic nutrients (uric acid and lecithin), to further stimulate biodegradation was investigated in laboratory microcosms over a 45-day period. Biodegradation was tracked by GC/MS analysis of aliphatic and polycyclic aromatic hydrocarbons components and the measured concentrations were corrected for abiotic removal by hopane normalizations. It was found that the saturated fraction of the residual oil is degraded more extensively than the aromatic fraction and the bacterial growth after an incubation period of approximately 3 weeks was much greater from the bacterial growth in the control. The results show that the treatments with inorganic or organic nutrients are equally effective over almost 30 days where C12-C35n-alkanes were degraded more than 97% and polyaromatic hydrocarbons with two or three rings were degraded more than 95% within 45 days. The results clearly show that the addition of nutrients to contaminated beach sand significantly enhanced the activity of indigenous microorganisms, as well as the removal of total recoverable petroleum hydrocarbons (TRPH) over a 45-day study period. PMID- 24229786 TI - Accurate analysis of polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs homologs in crude oil for improving the gas chromatography/mass spectrometry performance. AB - The common gas chromatography/mass spectrometry (GC/MS) approaches such as selective ion monitoring (SIM) or single ion extraction (SIE) from full scan data produce the error (over- or underestimation) estimates for the high level alkylated polycyclic aromatic hydrocarbons (PAHs). In order to rectify the error, the alkylated PAHs in the crude oil samples are quantified by deeply investigating the existing full scan data of 1D GC/MS, instead of resuming with the complex and inaccessible equipments (multidimensional gas chromatography or mass spectrometry). The aim of this study is to provide the detailed qualitative and quantitative basis data (confirming ions, relative abundance, retention indices, and area counts) of the high level alkylated PAHs by a comprehensive three-step method: (1) the potential confirming ions per isomer are selected by exploring the multiple fragment patterns formation mechanism; (2) the reasonable confirming ions are estimated by comparing extracted ion chromatography (EIC) of the potential confirming ions; (3) after deconvolution, composite chromatograms of the reasonable confirming ions illustrate the basis data by assigning peaks for target PAHs definitively. The validation data, resulting concentrations and diagnostic ratios for each homolog are compared with those obtained from SIM. The experimental data demonstrate that significant inaccurate identifications and concentration estimates are obtained when SIM mode is used for C4 Naphthalene (C4 N), C3 Phenanthrene (C3 P), C4 Phenanthrene (C4 P), C3 Dibenzothiophene (C3 D), C3 Fluorene (C3 F), C2-4 Chrysene (C2-4 C) and C1 Fluoranthene (C1 Flt). This study evaluates the usefulness of the previous fragmentation patterns, and confirms compound presence by GC/MS using the different spectral deconvolution software. This approach is developed as a broad screen for environmental samples (including petrol, diesel fuel and coal tar), with only the crude oil results being presented here. PMID- 24229787 TI - Effect of pre-grazing herbage mass on dairy cow performance, grass dry matter production and output from perennial ryegrass (Lolium perenne L.) pastures. AB - A grazing study was undertaken to examine the effect of maintaining three levels of pre-grazing herbage mass (HM) on dairy cow performance, grass dry matter (DM) production and output from perennial ryegrass (Lolium perenne L.) pastures. Cows were randomly assigned to one of three pre-grazing HM treatments: 1150 - Low HM (L), 1400 - Medium HM (M) or 2000 kg DM/ha - High HM (H). Herbage accumulation under grazing was lowest (P<0.01) on the L treatment and cows grazing the L pastures required more grass silage supplementation during the grazing season (+73 kg DM/cow) to overcome pasture deficits due to lower pasture growth rates (P<0.05). Treatment did not affect daily milk production or pasture intake, although cows grazing the L pastures had to graze a greater daily area (P<0.01) and increase grazing time (P<0.05) to compensate for a lower pre-grazing HM (P<0.01). The results indicate that, while pre-grazing HM did not influence daily milk yield per cow, adapting the practise of grazing low HM (1150 kg DM/ha) pasture reduces pasture DM production and at a system level may increase the requirement for imported feed. PMID- 24229788 TI - Outbreak of wound botulism in people who inject drugs, Norway, October to November 2013. AB - In October and November 2013, four cases of wound botulism were confirmed in people who inject drugs (PWID) in Norway. Two additional cases are suspected. Because of the international distribution pathways for heroin - the likely source of the outbreak - healthcare workers and public health authorities in other countries should remain vigilant for wound botulism in PWID. This outbreak serves as a reminder that countries should ensure access to botulinum antitoxin in case of outbreak situations. PMID- 24229789 TI - Carbapenemase-producing Klebsiella pneumoniae in the Czech Republic in 2011. AB - Carbapenemase-producing Enterobacteriaceae and Pseudomonas spp. are increasingly reported in many countries all over the world. Due to the resistance of those bacteria to almost all antibiotics (e.g.beta-lactams, aminoglycosides, fluoroquinolones),treatment options are seriously limited. In the Czech Republic, the incidence of carbapenemase-producing Enterobacteriaceae seems to be low, restricted to only three cases detected between 2009 and 2010.Here, we describe molecular typing of 15 carbapenemase-producing Klebsiella pneumoniae isolates identified in the Czech Republic during 2011. Five VIM-1-producing isolates belonging to sequence type (ST)11 and one VIM-4-producing isolate of ST1029 have been detected. blaVIM-1 and blaVIM-4 as a part of class 1 integrons were chromosomally located or carried by a plasmid belonging to A/C replicon type (blaVIM-4). KPC-3-producing isolates of ST512, recovered from six patients, caused an outbreak. Three more isolates producing KPC-2 enzyme belonged to ST258. Both blaKPCgenes were part of the Tn4401a transposon carried on plasmids of the pKpQIL type. The isolates were resistant to all antibiotics tested except colistin and/or gentamicin.Four of these 15 strains were recovered from patients repatriated to the Czech Republic from Greece and Italy. This is the first report of outbreaks caused by carbapenemase-producing Enterobacteriaceae in the Czech Republic. PMID- 24229790 TI - Trends in influenza vaccination behaviours--results from the CoPanFlu cohort, France, 2006 to 2011. AB - Controversies over the effectiveness and safety of the pandemic influenza A(H1N1)pdm09 vaccine in 2009/10 may have altered the influenza vaccination coverage in France after the pandemic season. The purpose of this study was to determine whether the pandemic affected seasonal influenza vaccination behaviours in the general population by analysing vaccination behaviours from 2006/07 to 2011/12 among the 1,451 subjects of the Cohort for Pandemic Influenza (CoPanFlu) France.We found that vaccination behaviours in 2010/11 and 2011/12 significantly differed from behaviours before the pandemic, with the notable exception of the targeted risk groups for seasonal influenza-related complications. Among the population with no risk factors,the post-pandemic influenza vaccine coverage decreased, with people aged 15 to 24 years and 45to 64 years being most likely to abandon vaccination.Therefore, this study documents a moderate negative effect of the 2009/10 pandemic episode on vaccination behaviours in the French metropolitan population that was apparent also in the following two seasons.Moreover, it does not exclude that the general trend of reduced vaccination has also affected certain targeted groups at high risk for complications. PMID- 24229791 TI - Ethics of mandatory vaccination for healthcare workers. AB - Healthcare workers (HCWs) are at increased risk of contracting infections at work and further transmitting them to colleagues and patients. Immune HCWs would be protected themselves and act as a barrier against the spread of infections and maintain healthcare delivery during outbreaks, but vaccine uptake rates in HCWs have often been low. In order to achieve adequate immunisation rates in HCWs, mandatory vaccination policies are occasionally implemented by healthcare authorities, but such policies have raised considerable controversy. Here we review the background of this debate, analyse arguments for and against mandatory vaccination policies, and consider the principles and virtues of clinical, professional, institutional and public health ethics. We conclude that there is a moral imperative for HCWs to be immune and for healthcare institutions to ensure HCW vaccination, in particular for those working in settings with high-risk groups of patients. If voluntary uptake of vaccination by HCWs is not optimal, patients' welfare, public health and also the HCW's own health interests should outweigh concerns about individual autonomy: fair mandatory vaccination policies for HCWs might be acceptable. Differences in diseases, patient and HCW groups at risk and available vaccines should be taken into consideration when adopting the optimal policy. PMID- 24229795 TI - A four-session acceptance and commitment therapy based intervention for depressive symptoms delivered by masters degree level psychology students: a preliminary study. AB - BACKGROUND: Depressive symptoms are one of the main reasons for seeking psychological help. Shorter interventions using briefly trained therapists could offer a solution to the ever-rising need for early and easily applicable psychological treatments. AIMS: The current study examines the effectiveness of a four-session Acceptance and Commitment Therapy (ACT) based treatment for self reported depressive symptoms administered by Masters level psychology students. METHOD: This paper reports the effectiveness of a brief intervention compared to a waiting list control (WLC) group. Participants were randomized into two groups: ACT (n = 28) and waiting list (n = 29). Long-term effects were examined using a 6 month follow-up. RESULTS: The treatment group's level of depressive symptoms (Beck Depression Inventory) decreased by an average of 47%, compared to an average decrease of 4% in the WLC group. Changes in psychological well-being in the ACT group were better throughout, and treatment outcomes were maintained after 6 months. The posttreatment "between-group" and follow-up "with-in group" effect sizes (Cohen's d) were large to medium for depressive symptoms and psychological flexibility. CONCLUSIONS: The results support the brief ACT-based intervention for sub-clinical depressive symptoms when treatment was conducted by briefly trained psychology students. It also contributes to the growing body of evidence on brief ACT-based treatments and inexperienced therapists. PMID- 24229796 TI - Resembling breast milk: influence of polyamine-supplemented formula on neonatal BALB/cOlaHsd mouse microbiota. AB - Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula). In addition to its nutritional value, breast milk contains bioactive substances that drive microbial colonisation and support immune system development, which are usually not present in infant formulas. Among these substances, polyamines have been described to be essential for intestinal and immune functions in newborns. However, their effect on the establishment of microbiota remains unclear. Therefore, the aim of the present study was to ascertain whether an infant formula supplemented with polyamines has an impact on microbial colonisation by modifying it to resemble that in breast-fed neonatal BALB/c mice. In a 4 d intervention, a total of sixty pups (14 d old) were randomly assigned to the following groups: (1) breast-fed group; (2) non-enriched infant formula-fed group; (3) three different groups fed an infant formula enriched with increasing concentrations of polyamines (mixture of putrescine, spermidine and spermine), following the proportions found in human milk. Microbial composition in the contents of the oral cavity, stomach and small and large intestines was analysed by quantitative PCR targeted at fourteen bacterial genera and species. Significantly different (P< 0.05) microbial colonisation patterns were observed in the entire gastrointestinal tract of the breast-fed and formula-fed mice. In addition, our findings demonstrate that supplementation of polyamines regulates the amounts of total bacteria, Akkermansia muciniphila, Lactobacillus, Bifidobacterium, Bacteroides-Prevotella and Clostridium groups to levels found in the breast-fed group. Such an effect requires further investigation in human infants, as supplementation of an infant formula with polyamines might contribute to healthy gastrointestinal tract development. PMID- 24229797 TI - Thermoregulation of nutrient-restricted hair ewes subjected to heat stress during late pregnancy. AB - In summers with severe hot environmental temperatures, thermoregulation is expected to be critical during the last third of gestation of hair ewes, and this effect can be overstated by suboptimal feeding conditions. Twenty-four multiparous hair sheep ewes with approximately 100d of pregnancy were randomly assigned to two treatments to evaluate the effects of nutritional restriction (NR) during late gestation on some serum metabolites, physiological variables, and thyroid hormone concentrations under intense heat load (maximum temperature 42-45 degrees C). Treatments were as follows: (1) control, ewes fed free choice wheat straw plus a concentrate at a rate of 500g/d, and (2) nutritionally restricted (NR) ewes, which were offered wheat straw only ad libitum. Body weight of NR ewes dropped 5.1kg (P<0.05), while control ewes gained 4.7kg during the study period. Rectal temperature was not affected (P>0.05) by feeding regime either in the morning or afternoon hours. Respiration rate was greater (P<0.05) in control ewes (20 and 40breaths/min higher in the day and night, respectively) on d 130 and 145 of pregnancy compared to NR ewes. Skin temperatures during the morning and afternoon were affected (P<0.05) by feeding regime at d 130 and 145 of pregnancy. In the morning, NR ewes presented greater (P<0.05) head and rump temperature at day 145 of gestation, and lower (P<0.05) udder temperatures at d 130 and 145 than control ewes. In the afternoon, skin temperatures of NR ewes were higher (P<0.05) in head and right flank on d 130 and 145 of pregnancy, and in udder at day 145 compared to control ewes. Serum glucose was higher (P<0.05) in NR ewes than control animals at day 145 of pregnancy. Serum cholesterol, triglyceride and thyroid hormones were not affected by nutritional restriction. Overall, it was found that nutritionally restricted ewes were less affected by intense heat loads than well-fed ewes, apparently due to the lower metabolic heat produced by this underfed animals. Also, it was apparent that the lower respiration rate of NR ewes was compensated by a greater body surface temperature. PMID- 24229798 TI - Beneath the surface: profiling blubber depth in pinnipeds with infrared imaging. AB - Infrared thermography (IRT) was assessed as a non-invasive tool to evaluate body condition in juvenile female harbor seals (Phoca vitulina), (n=6) and adult female Steller sea lions (Eumetopias jubatus), (n=2). Surface temperature determined by IRT and blubber depth assessed with portable imaging ultrasound were monitored concurrently at eight body sites over the course of a year in long term captive individuals under controlled conditions. Site-specific differences in surface temperature were noted between winter and summer in both species. Overall, surface temperature was slightly higher and more variable in harbor seals (9.8+/-0.6 degrees C) than Steller sea lions (9.1+/-0.5 degrees C). Limited site-specific relationships were found between surface temperature and blubber thickness, however, insulation level alone explained a very small portion of the variance. Therefore, while validated IRT data collection can potentially provide valuable information on the health, condition and metabolic state of an animal, it cannot provide a generalized proxy for blubber depth. PMID- 24229799 TI - Thermopreference, tolerance and metabolic rate of early stages juvenile Octopus maya acclimated to different temperatures. AB - Thermopreference, tolerance and oxygen consumption rates of early juveniles Octopus maya (O. maya; weight range 0.38-0.78g) were determined after acclimating the octopuses to temperatures (18, 22, 26, and 30 degrees C) for 20 days. The results indicated a direct relationship between preferred temperature (PT) and acclimated temperature, the PT was 23.4 degrees C. Critical Thermal Maxima, (CTMax; 31.8+/-1.2, 32.7+/-0.9, 34.8+/-1.4 and 36.5+/-1.0) and Critical Thermal Minima, (CTMin; 11.6+/-0.2, 12.8+/-0.6, 13.7+/-1.0, 19.00+/-0.9) increased significantly (P<0.05) with increasing acclimation temperatures. The endpoint for CTMax was ink release and for CTMin was tentacles curled, respectively. A thermal tolerance polygon over the range of 18-30 degrees C resulted in a calculated area of 210.0 degrees C(2). The oxygen consumption rate increased significantly alpha=0.05 with increasing acclimation temperatures between 18 and 30 degrees C. Maximum and minimum temperature quotients (Q10) were observed between 26-30 degrees C and 22-26 degrees C as 3.03 and 1.71, respectively. These results suggest that O. maya has an increased capability for adapting to moderate temperatures, and suggest increased culture potential in subtropical regions southeast of Mexico. PMID- 24229800 TI - Thermal relations of dwarf caiman, Paleosuchus palpebrosus, in a hillside stream: evidence for an unusual thermal niche among crocodilians. AB - Body temperatures of 13 Paleosuchus palpebrosus, 7 males and 6 females, were monitored by radio-telemetry during cold periods (dry season) and warm periods (wet and dry seasons) in a stream draining into the Brazilian Pantanal. The mass of the caimans varied from 2.5 to 20.0kg, and snout-vent length from 47.5 to 95.0cm. Mean monthly body temperature was 21.6 degrees C, and varied from 20.1 to 25.6 degrees C throughout the year. Body temperature was correlated with air and water temperature but did not differ between males and females. Unlike all other crocodilians investigated in detail to date, the caimans did not show evidence of attempts to obtain higher body temperatures when ambient temperatures were low, and had low and generally constant temperatures in relation to the surrounding air and water throughout the year. The caimans remained in burrows during cold periods in the dry season, which may explain why they did not seek higher temperatures. Tolerance of relatively low and constant body temperatures may be a key adaptation of species of Paleosuchus, allowing them to occupy environments inhospitable to other crocodilians. PMID- 24229801 TI - Habituation of the metabolic and ventilatory responses to cold-water immersion in humans. AB - An experiment was undertaken to answer long-standing questions concerning the nature of metabolic habituation in repeatedly cooled humans. It was hypothesised that repeated skin and deep-body cooling would produce such a habituation that would be specific to the magnitude of the cooling experienced, and that skin cooling alone would dampen the cold-shock but not the metabolic response to cold water immersion. Twenty-one male participants were divided into three groups, each of which completed two experimental immersions in 12 degrees C water, lasting until either rectal temperature fell to 35 degrees C or 90min had elapsed. Between these two immersions, the control group avoided cold exposures, whilst two experimental groups completed five additional immersions (12 degrees C). One experimental group repeatedly immersed for 45min in average, resulting in deep-body (1.18 degrees C) and skin temperature reductions. The immersions in the second experimental group were designed to result only in skin temperature reductions, and lasted only 5min. Only the deep-body cooling group displayed a significantly blunted metabolic response during the second experimental immersion until rectal temperature decreased by 1.18 degrees C, but no habituation was observed when they were cooled further. The skin cooling group showed a significant habituation in the ventilatory response during the initial 5min of the second experimental immersion, but no alteration in the metabolic response. It is concluded that repeated falls of skin and deep-body temperature can habituate the metabolic response, which shows tissue temperature specificity. However, skin temperature cooling only will lower the cold-shock response, but appears not to elicit an alteration in the metabolic response. PMID- 24229802 TI - Numerical analysis for determination of the presence of a tumor and estimation of its size and location in a tissue. AB - This article deals with the numerical analysis to ascertain the presence of a tumor and to estimate its size and location in a tissue. Heat transfer in the tissue is modeled using the Pennes bioheat transfer equation, and is solved using the finite volume method. Consideration is given to 1-D brain and breast tissues. Temperature distributions in the tissues are specific to the tumor grades, its locations and sizes, and these are different than that of a normal tissue. With temperature distribution known a priori, estimations of the position and the size of a tumor are done using the inverse analysis. The proposed approach gives a correct estimation of the presence of a tumor and its location and size. PMID- 24229803 TI - Influences of sex, ontogeny and body size on the thermal ecology of Liolaemus lutzae (Squamata, Liolaemidae) in a restinga remnant in Southeastern Brazil. AB - Variations in body temperature (Tb) of lizards can be partially explained by intrinsic factors such as sex, ontogeny and body size. Liolaemus lutzae is a lizard species restricted to restingas in the Brazilian coast in the state of Rio de Janeiro. Herein, we studied sexual dimorphism and influences of sex, ontogeny, and body size to the Tb of L. lutzae. Adult males were larger than adult females, probably due to both intersexual selection and intra-sexual selection. There was intersexual difference in lizards' Tb (males hotter than females), but Tb did not differ after factored out for the effects of body size. The mean Tb of juvenile lizards was higher than that of adults after factored out for the effect of body mass. It is possible that adults may have excluded juveniles from microhabitats with better thermal regimes. Also, this might have occurred due to requirements of juveniles to maintain high growth rates. Forage searching for prey by juveniles also exposes them to high environmental temperatures. Juveniles also may have higher Tb than co-specific adults (relative to body mass) to favor prey capture. In absolute values, adult lizards tended to use microhabitats with lower temperatures than that used by juveniles, possibly to avoid risks of overheating and death. Body temperature and snout-vent length were positively related, as well as body temperature and body mass, presumably caused by the thermal inertia of the bodies (trend of a body to resist to changes in its temperature). Intrinsic factors such as sex, ontogeny and body size can affect the thermal ecology of L. lutzae, despite coastal habitat features to which they are exposed also influences the body temperature of active lizards in restinga habitats. PMID- 24229804 TI - Seasonal thermoregulation in the burrowing parrot (Cyanoliseus patagonus). AB - Birds exposed to seasonal environments are faced with the problem of maintaining thermogenic homoeostasis. Previous studies have established that birds native to the Holarctic increase their Resting Metabolic Rate at different ambient temperatures (RMRTa) and Basal Metabolic Rate (BMR) in winter as an adaptation to cold temperature since winters are more severe, while their non-Holarctic counterparts generally decrease their winter BMR as an energy saving mechanism during unproductive and dry winter months. In this study, we examined seasonal thermoregulation in the burrowing parrot (Cyanoliseus patagonus), a colonial psittacine native to the Patagonian region of Argentina, a region with an unpredictable environment. We found significantly higher mass specific RMRTa and BMR in summer than in winter. Both summer and winter BMR of the species fell within the predicted 95% confident interval for a parrot of its size. Body mass was significantly higher in winter than in summer. The burrowing parrot had broad thermo-neutral zones in winter and summer. The circadian rhythm of core body temperature (Tb) of burrowing parrots was not affected by season, showing that this species regulated its Tb irrespective of season. These results suggest that the burrowing parrots' seasonal thermoregulatory responses represent that of energy conservation which is important in an unpredictable environment. PMID- 24229805 TI - Healthcare workers and measles-mumps-rubella (MMR) status: how worried should we be about further outbreaks? AB - Recently, a number of outbreaks of measles and mumps have occurred within the UK and Europe. Healthcare workers (HCWs) are at risk of contracting and transmitting disease to patients and staff. To examine this risk at the point of entry to healthcare, we assessed the serological results of new HCWs presenting for pre placement clearance without evidence of measles-mumps-rubella (MMR) immunity between 1 April 2010 and 31 March 2012. Overall rates of serological positivity to MMR across all age groups were 88.2%, 68.8% and 93.9%, respectively. With regard to measles and mumps, there were statistically significant decreases in the percentage of HCWs born after 1980 that had positive serology (P < 0.05). No such differences were seen between healthcare groups. Most seronegative HCWs accepted MMR vaccination. Despite our entry-level findings, the ongoing risk of a MMR outbreak within this cohort of HCWs appears low. PMID- 24229806 TI - Financial and testamentary capacity evaluations: procedures and assessment instruments underneath a functional approach. AB - BACKGROUND: Mental health professionals are frequently involved in mental capacity determinations. However, there is a lack of specific measures and well defined procedures for these evaluations. The main purpose of this paper is to provide a review of financial and testamentary capacity evaluation procedures, including not only the traditional neuropsychological and functional assessment but also the more recently developed forensic assessment instruments (FAIs), which have been developed to provide a specialized answer to legal systems regarding civil competencies. METHODS: Here the main guidelines, papers, and other references are reviewed in order to achieve a complete and comprehensive selection of instruments used in the assessment of financial and testamentary capacity. RESULTS: Although some specific measures for financial abilities have been developed recently, the same is not true for testamentary capacity. Here are presented several instruments or methodologies for assessing financial and testamentary capacity, including neuropsychological assessment, functional assessment scales, performance based functional assessment instruments, and specific FAIs. CONCLUSIONS: FAIs are the only specific instruments intended to provide a specific and direct answer to the assessment of financial capacity based on legal systems. Considering the need to move from a diagnostic to a functional approach in financial and testamentary capacity evaluations, it is essential to consider both general functional examination as well as cognitive functioning. PMID- 24229808 TI - [Nephrotic proteinuria in hypertensive nephrosclerosis: clinical and evolution characteristics]. AB - BACKGROUND AND OBJECTIVE: Nephrotic range proteinuria can occur in patients with biopsy proven hypertensive nephrosclerosis (HN). We analysed the differential clinical and evolution characteristics of these patients compared with other glomerular diseases. MATERIAL AND METHOD: This is a case-control descriptive analysis obtained from the renal pathology registry of our hospital. Clinical features, treatment and evolution of these patients (cases) were compared with nephrotic patients with other glomerular diseases (controls). RESULTS: Five point one percent of biopsies with HN diagnosis. Case/control characteristics were: proteinuria 4.7 [3-11.4] versus 5.5 [3-28.1] g/24h/1.73m(2) (P=NS). Normal albumin compared with controls (39.5 [6.4] versus 29.4 [10] g/dL; P=.001), significant oedemas only in 10 versus 63% of controls. HN were older (58.8 [12.6] versus 45.5 [19.6] years), had longer hypertension duration before renal biopsy and more previous cardiovascular events (39 versus 16%). Mean blood pressure was higher (166/90 versus 133/75mmHg; P=.01) and had worse renal outcome. CONCLUSIONS: HN must be included in the differential diagnosis of nephrotic range proteinuria in hypertensive patients. The absence of oedema and normal serum albumin are distinctive clinical characteristics that can help in decision-making before performing a renal biopsy. PMID- 24229807 TI - Evolution of parasitism along convergent lines: from ecology to genomics. AB - SUMMARY From hundreds of independent transitions from a free-living existence to a parasitic mode of life, separate parasite lineages have converged over evolutionary time to share traits and exploit their hosts in similar ways. Here, we first summarize the evidence that, at a phenotypic level, eukaryotic parasite lineages have all converged toward only six general parasitic strategies: parasitoid, parasitic castrator, directly transmitted parasite, trophically transmitted parasite, vector-transmitted parasite or micropredator. We argue that these strategies represent adaptive peaks, with the similarities among unrelated taxa within any strategy extending to all basic aspects of host exploitation and transmission among hosts and transcending phylogenetic boundaries. Then, we extend our examination of convergent patterns by looking at the evolution of parasite genomes. Despite the limited taxonomic coverage of sequenced parasite genomes currently available, we find some evidence of parallel evolution among unrelated parasite taxa with respect to genome reduction or compaction, and gene losses or gains. Matching such changes in parasite genomes with the broad phenotypic traits that define the convergence of parasites toward only six strategies of host exploitation is not possible at present. Nevertheless, as more parasite genomes become available, we may be able to detect clear trends in the evolution of parasitic genome architectures representing true convergent adaptive peaks, the genomic equivalents of the phenotypic strategies used by all parasites. PMID- 24229809 TI - Persistent cognitive changes in breast cancer patients 1 year following completion of chemotherapy. AB - Numerous studies have shown that there are acute cognitive side-effects of chemotherapy for breast cancer. Presumably, patients are more concerned about chronic treatment effects. This report from a prospective longitudinal study compares cognitive functioning in 56 breast cancer patients 1 year after chemotherapy to that of 56 healthy individuals. Neuropsychological test scores were combined into verbal memory, visual memory, working memory, and processing speed scores, as well as an overall summary score, and analyzed using multi-level growth modeling. Frequency of cognitive decline was assessed using regression based change scores. There was significant rebound in the overall summary score from end of treatment to 1-year follow-up as well as a substantial reduction in the frequency of cognitive decline. However, more than one-third of the breast cancer patients who showed cognitive decline immediately following completion of chemotherapy showed persistent cognitive decline 1 year later. Furthermore, recovery was not seen in all cognitive domains. In fact, the rebound was significant only for working memory. Longer multi-site studies are recommended to explore the risk factors for and the permanence of these longer-term cognitive effects. PMID- 24229810 TI - Dietary carbohydrate composition modifies the milk N efficiency in late lactation cows fed low crude protein diets. AB - Nitrogen emissions from dairy cows can be readily decreased by lowering the dietary CP concentration. The main objective of this work was to test whether the milk protein yield reduction associated with low N intakes could be partially compensated for by modifying the dietary carbohydrate composition (CHO). The effects of CHO on digestion, milk N efficiency (milk N/N intake; MNE) and animal performance were studied in four Jersey cows fed 100% or 80% of the recommended protein requirements using a 4*4 Latin square design. Four iso-energetic diets were formulated to two different CHO sources (starch diets with starch content of 34.3% and NDF at 32.5%, and fiber diets with starch content of 5.5% and NDF at 49.1%) and two CP levels (Low=12.0% and Normal=16.5%). The apparent digestible organic matter intake (DOMI) and the protein supply (protein digestible in the small intestine; PDIE) were similar between starch and fiber diets. As planned, microbial N flow (MNF) to the duodenum, estimated from the urinary purine derivatives (PD) excretion, was similar between Low and Normal CP diets. However, the MNF and the efficiency of microbial synthesis (g of microbial N/kg apparently DOMI) were higher for starch v. fiber diets. Milk and milk N fractions (CP, true protein, non-protein N (NPN)) yield were higher for starch compared with fiber diets and for Normal v. Low CP diets. Fecal N excretion was similar across dietary treatments. Despite a higher milk N ouput with starch v. fiber diets, the CHO modified neither the urinary N excretion nor the milk urea-N (MUN) concentration. The milk protein yield relative to both N and PDIE intakes was improved with starch compared with fiber diets. Concentrations of beta hydroxybutyrate, urea and Glu increased and those of glucose and Ala decreased in plasma of cows fed starch v. fiber diets. On the other hand, plasma concentration of albumin, urea, insulin and His increased in cows fed Normal compared with Low CP diets. This study showed that decreasing the dietary CP proportion from 16.5% to 12.0% increases and decreases considerably the MNE and the urinary N excretion, respectively. Moreover, present results show that at similar digestible OM and PDIE intakes, diets rich in starch improves the MNE and could partially compensate for the negative effects of Low CP diets on milk protein yield. PMID- 24229811 TI - Role of the General Surgeon in the Early Diagnosis and Treatment of Charcot Foot. AB - INTRODUCTION: The Charcot foot (CF) consists of a progressive deterioration of the bones and joints, most common in diabetic patients with advanced neuropathy. The great problem is that can be confused with other processes, delaying the diagnosis and specific treatment. The aim is to analyze the cases of CF diagnosed in our hospital and especially to highlight the role of the general surgeon. MATERIAL AND METHODS: Retrospective study of all registered cases diagnosed of CF between the diabetic population of our Department of Health. A review of the literature was performed. RESULTS: From 2008 to 2012, there 7 cases of CF were diagnosed (prevalence 1:710). Two of the patients were diagnosed erroneously of cellulitis. The average time of delay in the diagnosis was 10 weeks (minimum 1, maximum 24). The initial treatment was immobilization of the extremity. Once the edema was eliminated, an offload orthesis was placed according to Sanders's anatomical classification. Evolution was favorable in 5 patients, 1 patient needed amputation, and other one died of acute cardiac pathology. CONCLUSIONS: The CF is a more frequent pathology than we believe. The general surgeon is the fundamental prop in the diagnosis and initial treatment. Before the presence of inflammation and edema of the foot in a patient with diabetes and severe neuropathy, once cellulitis, osteomyelitis, and TVP are ruled out, Charcot neuroarthropathy should be considered. PMID- 24229812 TI - [Obstructive jaundice caused by a mucinous adenocarcinoma of the appendix in a patient with intestinal malrotation]. PMID- 24229813 TI - mRNA Expression of lipogenic enzymes in mammary tissue and fatty acid profile in milk of dairy cows fed flax hulls and infused with flax oil in the abomasum. AB - In the present study, the effect of flax hulls with or without flax oil bypassing the rumen on the expression of lipogenic genes in the mammary tissue of dairy cows was investigated. A total of eight dairy cows were used in a replicated 4 * 4 Latin square design. There were four periods of 21 d each and four treatments: control diet with no flax hulls (CONT); diet with 9.88 % flax hulls in the DM (HULL); control diet with 500 g flax oil/d infused in the abomasum (COFO); diet with 9.88 % flax hulls in the DM and 500 g flax oil/d infused in the abomasum (HUFO). A higher mRNA abundance of sterol regulatory element binding transcription factor, fatty acid (FA) synthase, lipoprotein lipase (LPL), PPARgamma1, stearoyl-CoA desaturase (SCD) and acetyl-coenzyme A carboxylase-alpha was observed in cows fed HULL than in those fed CONT, and HUFO had the opposite effect. Compared with CONT, COFO and HUFO lowered the mRNA abundance of SCD, which may explain the lower proportions of MUFA in milk fat with flax oil infusion. The mRNA abundance of LPL in mammary tissue and proportions of long chain FA in milk fat were higher in cows fed COFO than in those fed CONT. The highest proportions of trans FA were observed when cows were fed HULL. The present study demonstrates that flax hulls with or without flax oil infusion in the abomasum can affect the expression of lipogenic genes in the mammary tissue of dairy cows, which may contribute to the improvement of milk FA profile. PMID- 24229814 TI - The reality of China. PMID- 24229815 TI - A review of JACC articles on the topic of heart rhythm disorders: 2011-2012. PMID- 24229816 TI - Advances in diagnosing peanut allergy. AB - Peanut allergy is often severe, potentially fatal, usually persistent, and appears to have increased in prevalence. An accurate diagnosis is essential because there is a significant burden on quality of life. The tools available for diagnosis include the medical history, skin prick test (SPT), determination of serum peanut-specific IgE antibodies (PN-IgE), and medically supervised oral food challenges. Numerous studies, almost exclusively in children, have correlated clinical outcomes against SPTs and PN-IgE with informative results. The diagnostic utility of SPT and PN-IgE is maximized by considering the degree of positive result and consideration of the medical history (a priori estimation of risk). Emerging tests that evaluate IgE binding to specific proteins in peanut (component testing) add important additional diagnostic information in specific settings. Studies are increasingly focused on how the results of tests considered in combination (or performed serially) may increase diagnostic accuracy. Here, we review the utility of currently available tests and provide suggestions on how to best use them to accurately predict peanut allergy. Still, the physician supervised oral food challenge remains the most definitive test available. PMID- 24229817 TI - Peanut oral immunotherapy: is it ready for clinical practice? AB - The prevalence of peanut allergy in the United States and other Westernized countries has tripled in the past 15 years, now affecting more than 1% of the population. Strict peanut avoidance is the current standard of care. In the past decade, a number of small, largely uncontrolled clinical trials have suggested that oral immunotherapy (OIT) can effectively desensitize most children with peanut allergy. Some in the allergy community now feel that OIT is ready for clinical practice. In this review, the evidence base in the medical literature is examined. Although peanut OIT shows promise, the evidence currently available on its effectiveness, risk benefit, and potential long-term consequences is insufficient to support its use in clinical practice. Appropriately designed, prospective clinical trials are urgently needed to determine whether OIT is a safe, effective form of therapy for food allergy. PMID- 24229818 TI - Evaluation of food allergy in patients with atopic dermatitis. AB - Atopic dermatitis (AD) is a common skin disease characterized by inflammatory, chronically relapsing and pruritic eczematous flares. Its estimated incidence is 10% to 30% in children. Food allergy has been well documented in approximately one-third of children with a moderate-to-severe AD. Cow's milk, hen's egg, peanut, wheat, soy, nuts, and fish are responsible for >90% of food allergy in children with AD. The incidence and type of food can vary with age. In infants, cow's milk, hen's egg, peanut, and soy and, in older children, wheat, fish, tree nuts, and shellfish are the most common food allergens. Birch-associated foods have also been described as potential triggers of AD in children as well as in adults. The diagnosis of food allergy in AD is currently based on the clinical history, skin prick tests, or blood test screening, followed by an elimination diet and/or standardized oral food challenge. Once an underlying food allergy is confirmed, the avoidance of the incriminated food is generally recommended and usually leads to an improvement of the AD. Follow-up clinical evaluation with a detailed history and tracking of the level of specific IgE to implicated foods are typically used to evaluate the development of clinical tolerance, further confirmed by an oral food challenge. PMID- 24229819 TI - Primary prevention of allergic disease through nutritional interventions. AB - With the rising prevalence of atopic disease, primary prevention may play a role in reducing its burden, especially in high-risk infants. With this in mind, the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was charged with the task of developing recommendations for primary care physicians and specialists about the primary prevention of allergic disease through nutritional interventions according to current available literature and expert opinion. Recommendations that are supported by data are as follows. Avoidance diets during pregnancy and lactation are not recommended at this time, but more research is necessary for peanut. Exclusive breast-feeding for at least 4 and up to 6 months is endorsed. For high-risk infants who cannot be exclusively breast-fed, hydrolyzed formula appears to offer advantages to prevent allergic disease and cow's milk allergy. Complementary foods can be introduced between 4 and 6 months of age. Because no formal recommendations have been previously provided about how and when to introduce the main allergenic foods (cow's milk, egg, soy, wheat, peanut, tree nuts, fish, shellfish), these are now provided, and reasons to consider allergy consultation for development of a personalized plan for food introduction are also presented. PMID- 24229820 TI - What the world needs now: JACI: In Practice. PMID- 24229821 TI - Vocal cord dysfunction related to water-damaged buildings. AB - BACKGROUND: Vocal cord dysfunction (VCD) is the intermittent paradoxical adduction of the vocal cords during respiration, resulting in variable upper airway obstruction. Exposure to damp indoor environments is associated with adverse respiratory health outcomes, including asthma, but its role in the development of VCD is not well described. OBJECTIVE: We describe the spectrum of respiratory illness in occupants of 2 water-damaged office buildings. METHODS: The National Institute for Occupational Safety and Health conducted a health hazard evaluation that included interviews with managers, a maintenance officer, a remediation specialist who had evaluated the 2 buildings, employees, and consulting physicians. In addition, medical records and reports of building evaluations were reviewed. Diagnostic evaluations for VCD had been conducted at the Asthma and Allergy Center of the Medical College of Wisconsin. RESULTS: Two cases of VCD were temporally related to occupancy of water-damaged buildings. The patients experienced cough, chest tightness, dyspnea, wheezing, and hoarseness when in the buildings. Spirometry was normal. Methacholine challenge did not show bronchial hyperreactivity but did elicit symptoms of VCD and inspiratory flow volume loop truncation. Direct laryngoscopy revealed vocal cord adduction during inspiration. Coworkers developed upper and lower respiratory symptoms; their diagnoses included sinusitis and asthma, consistent with recognized effects of exposure to indoor dampness. Building evaluations provided evidence of water damage and mold growth. CONCLUSION: VCD can occur with exposure to water-damaged buildings and should be considered in exposed patients with asthma-like symptoms. PMID- 24229822 TI - Association between consistent omalizumab treatment and asthma control. AB - BACKGROUND: Omalizumab is indicated for patients with moderate-to-severe allergic asthma with inadequately controlled symptoms. OBJECTIVE: We evaluated the association between consistent omalizumab treatment and asthma control. METHODS: Health insurance claims from the MarketScan database (2002Q1-2011Q2) were analyzed. Asthmatic patients with >=12 months of continuous insurance coverage after the first omalizumab claim (index date) after 6 months of continuous omalizumab use were included. A 12-month landmark period was used to assess treatment consistency, defined as uninterrupted treatment without a gap of >=28 days in omalizumab use. The effect of consistent omalizumab treatment on asthma control between months 13 and 24 was evaluated. Multivariate time-varying Cox regressions were also conducted to assess the adjusted effect of treatment interruption on asthma control from month 1 to month 24. RESULTS: A total of 3044 patients (mean age, 48.5 years; female, 62%) formed the study population. Patients consistent with omalizumab treatment at 12 months (39% of patients) were less likely to have an uncontrolled asthma event during months 13 to 24 with only 49% of patients experiencing one event compared with 54% in the non consistent subgroup (P = .02). In addition, consistent omalizumab treatment at 12 months was associated with a 51% reduction in the mean number of asthma-related emergency department (ED) visits per patient and a 28% reduction in asthma-related hospitalizations. Multivariate analyses corroborated these findings (hazard ratio for consistent vs non-consistent: risk of short-acting beta2-agonists prescription, oral corticosteroids prescription, ED visit, or hospitalization, 0.76; 95% CI, 0.69-0.83]). CONCLUSION: This analysis showed that consistent omalizumab treatment was associated with significant reductions in ED visits and hospitalizations. PMID- 24229823 TI - Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. AB - BACKGROUND: Budesonide inhalation suspension (BIS) and montelukast provide acceptable asthma control, whereas overall measures favored BIS in children aged 2 to 8 years with mild persistent asthma. OBJECTIVE: We compared BIS and montelukast over a 1-year period in children aged 2 to 4 years with asthma. METHODS: Data were derived from a 52-week, open-label, randomized, active controlled, multicenter study (NCT00641472). Children with mild asthma received either BIS 0.5 mg or montelukast 4 to 5 mg once daily. Patients were stepped up to twice-daily BIS or oral corticosteroids for mild or severe asthma worsening, respectively. Primary efficacy assessment was time to first additional asthma medication for exacerbation over 52 weeks. RESULTS: Two hundred two patients, age 2 to 4 years, received BIS (n = 105) or montelukast (n = 97). No difference was observed between the BIS and montelukast groups in median time to first additional asthma medication over 52 weeks (183 vs 86 days). Statistically significant differences were observed in favor of BIS over montelukast in the percentage of patients requiring oral steroids at 52 weeks (21.9% vs 37.1%; P = .022), the rate (number/patient/year) of additional courses of medication (1.35 vs 2.30; P = .003), the rate of additional oral steroid therapy (0.44 vs 0.88; P = .008), and caregivers' ability to manage the patient's symptoms (P = .026). Both treatments were well tolerated. CONCLUSION: BIS and montelukast provided acceptable asthma control in children aged 2 to 4 years with mild persistent asthma with no significant difference between treatments in the primary end point; however, several secondary outcomes showed statistically significant differences (and many had numerical differences) in favor of BIS over montelukast. PMID- 24229824 TI - Leukotriene receptor antagonists in allergic eye disease: a systematic review and meta-analysis. AB - BACKGROUND: Allergic eye diseases are common and cause significant morbidity. Leukotrienes are implicated in the pathogenesis of seasonal and perennial allergic conjunctivitis (AC), commonly seen in conjunction with allergic rhinitis, and in vernal keratoconjunctivitis and atopic keratoconjunctivitis. OBJECTIVES: To assess the available evidence for an effect of leukotriene receptor antagonists (LTRAs) on the ocular symptoms of allergic eye diseases. METHODS: Selected studies, identified with systematic review search methods, were single/double-blind, randomized, controlled trials that compared LTRAs with other common treatments. RESULTS: Eighteen trials, using the LTRA montelukast (in AC only), were identified. Six studies were suitable for meta-analysis, in patients with seasonal AC [treated over a 2-week period, symptoms scored 0 (mild) to 3 (severe)]. These trials were at low risk of bias without significant heterogeneity. Six trials were analyzed and showed that montelukast improved patients' ocular symptoms to a greater extent than placebo, with a difference in mean change-from-baseline score of -0.10 (95% CI, -0.14 to -0.07; P < .00001). Three trials compared montelukast with oral antihistamine. The difference in mean change-from-baseline score was 0.08 (95% CI, 0.02 to 0.14; P = .007), in favor of antihistamines. Two trials compared montelukast and oral antihistamine with placebo. The difference in mean change-from-baseline score was -0.30 (95% CI, 0.38 to -0.21; P < .00001), in favor of combination treatment. CONCLUSIONS: In seasonal AC LTRAs are more efficacious than placebo but less efficacious than oral antihistamines in adult patients. Clinical trials should be conducted to determine whether combination treatment with LTRA and oral antihistamine has a synergistic effect. Further research is required to clarify the role of LTRAs in other allergic eye diseases. PMID- 24229825 TI - The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations. AB - BACKGROUND: Increasing data suggest that analysis of IgE to peanut components can be clinically helpful and possibly more accurate than IgE to whole peanut. Not all studies examining this topic, however, have used prospective samples, multiple components, and peanut challenges. OBJECTIVE: We sought to determine the utility of peanut component testing, using a standardized, commercially available test done before oral peanut challenge in various populations of patients with suspected peanut allergy from 2 different countries. METHODS: IgE to whole peanut and the recombinant allergen components Ara h 1, 2, 3, and 8 were analyzed from serum samples drawn before double-blind peanut challenge from 4 distinct cohorts of patients with suspected peanut allergy from 2 nations (United States and Sweden). RESULTS: Patients (n = 167; median age, 11.7 years; interquartile range, 7.0-15.0 years) had serum analyzed for peanut components and completed an oral food challenge to peanut. Although IgE to peanut was the most sensitive test (0.93), Ara h 2 was the most specific (0.92) and provided the best positive predictive value (0.94) of all the tests. Ara h 2 was also the best overall diagnostic test by receiver operating characteristic analysis (area under the curve, 0.84; P < .05). CONCLUSIONS: In patients with suspected peanut allergy, IgE to peanut is a sensitive test but is not specific. IgE to Ara h 2 is a more specific and more accurate diagnostic test in this sampling of patients with suspected peanut allergy. Given each tests attributes, a stepwise approach to testing may provide clinicians with a way to minimize the need for peanut challenges. PMID- 24229827 TI - Advancing the science of adherence measurement: implications for the clinician. PMID- 24229826 TI - Use of metered-dose inhaler electronic monitoring in a real-world asthma randomized controlled trial. AB - BACKGROUND: Electronic monitoring of inhaled asthma medications is one method to measure medication adherence and patterns of use. Information on the performance of monitors in a randomized controlled trial allows researchers and clinicians to understand their utility and limitations. The Smartinhaler Tracker is an electronic monitor for metered-dose inhalers (MDIs) that records the date, time, and number of actuations. OBJECTIVE: To determine the performance of the Smartinhaler monitors used in a 24-week randomized controlled trial of 303 patients with asthma in a real-world setting. METHODS: Prestudy use checks involved 2 actuations of the MDI, with a further 2 performed 2 hours later. Within-study monitor checks, performed before dispensing at clinic visits 2 to 4, included a computerized check of monitor clock function, actuation accuracy, and battery life. Within-study data checks involved computerized checks of monitor clock function before data upload. RESULTS: Two thousand six hundred seventy eight of 2728 monitors (98.2%) passed prestudy use checks. Seventy-six of 2642 monitors (2.9%) dispensed to participants failed within-study monitor checks. Fifty-one of 2642 monitors (1.9%) malfunctioned before data upload, mostly as a result of fluid immersion. Ninety-three of 2642 monitors (3.5%) were lost or thrown away by participants. Complete data was available from 2498 of 2642 dispensed monitors (94.5%) and 2498 of 2549 returned monitors (98.0%). CONCLUSIONS: The Smartinhaler Tracker is a reliable monitor for measuring MDI use in a real-world setting. Use of extensive monitor and data-checking protocols reduces data loss. In a research or clinical setting, the use of a validated and reliable electronic monitor represents the reference standard for assessing patterns of medication use. PMID- 24229828 TI - Generalized bullous eruption after routine vaccination in a child with diffuse cutaneous mastocytosis. PMID- 24229829 TI - Perplexing cases of allergy to salami. PMID- 24229830 TI - Near fatal anaphylaxis from orally administered gelatin capsule. PMID- 24229831 TI - Evaluation of Ara h2 IgE thresholds in the diagnosis of peanut allergy in a clinical population. PMID- 24229832 TI - Addition of mycophenolate mofetil to tacrolimus is associated with decreases in food-specific IgE levels in a pediatric patient with liver transplantation associated food allergy. PMID- 24229833 TI - A patient experiencing anaphylaxis and urticaria, in some cases preceded by ingestion of red meat. PMID- 24229836 TI - Changing of the guard, 2014. PMID- 24229841 TI - Geographic distribution of Theileria sp. (buffalo) and Theileria sp. (bougasvlei) in Cape buffalo (Syncerus caffer) in southern Africa: implications for speciation. AB - Strict control measures apply to movement of buffalo in South Africa including testing for Theileria parva, the causative agent of Corridor disease in cattle. The official test is a real-time hybridization PCR assay that amplifies the 18S rRNA V4 hyper-variable region of T. parva, T. sp. (buffalo) and T. sp. (bougasvlei). Mixed infections with the latter organisms affect diagnostic sensitivity due to PCR suppression. While the incidence of mixed infections in the Corridor disease endemic region of South Africa is significant, little information is available on the specific distribution and prevalence of T. sp. (buffalo) and T. sp. (bougasvlei). Specific real-time PCR assays were developed and a total of 1211 samples known to harbour these parasites were screened. Both parasites are widely distributed in southern Africa and the incidence of mixed infections with T. parva within the endemic region is similar (~25-50%). However, a significant discrepancy exists in regard to mixed infections of T. sp. (buffalo) and T. sp. (bougasvlei) (~10%). Evidence for speciation between T. sp. (buffalo) and T. sp. (bougasvlei) is supported by phylogenetic analysis of the COI gene, and their designation as different species. This suggests mutual exclusion of parasites and the possibility of hybrid sterility in cases of mixed infections. PMID- 24229842 TI - A cross-lagged panel model examining protective behavioral strategies: are types of strategies differentially related to alcohol use and consequences? AB - Protective behavioral strategies (PBS) are skills that can be used to reduce the risk of alcohol-related negative consequences. Studies have shown that, in general, PBS are related to less alcohol consumption and fewer negative consequences; however, other studies have suggested that not all types of PBS (e.g., stopping/limiting drinking [SLD], manner of drinking [MOD] and serious harm reduction [SHR]) are equally effective at reducing alcohol risk. In addition, few studies have explored the longitudinal relationships among PBS, alcohol use and consequences. Using a sample of heavy drinking college students (N=338), the current study examined PBS use, alcohol consumption and consequences across two time points three months apart. Cross-lagged panel models revealed that MOD predicted a reduction in alcohol use and negative consequences. SHR was longitudinally related to fewer negative consequences, but unrelated to alcohol use. SLD was not associated with drinking or consequences at follow-up. These results highlight the need for future research to examine the effects of different types of PBS and have implications for alcohol intervention programs that incorporate PBS skills training. PMID- 24229843 TI - A longitudinal study of electronic cigarette users. AB - OBJECTIVE: To assess behavior change over 12 months in users of e-cigarettes ("vapers"). METHODS: Longitudinal Internet survey, 2011 to 2013. Participants were enrolled on websites dedicated to e-cigarettes and smoking cessation. We assessed use of e-cigarettes and tobacco among the same cohort at baseline, after one month (n=477) and one year (n=367). RESULTS: Most participants (72%) were former smokers, and 76% were using e-cigarettes daily. At baseline, current users had been using e-cigarettes for 3 months, took 150 puffs/day on their e-cigarette and used refill liquids containing 16 mg/ml of nicotine, on average. Almost all the daily vapers at baseline were still vaping daily after one month (98%) and one year (89%). Of those who had been vaping daily for less than one month at baseline, 93% were still vaping daily after one month, and 81% after one year. In daily vapers, the number of puffs/day on e-cigarettes remained unchanged between baseline and one year. Among former smokers who were vaping daily at baseline, 6% had relapsed to smoking after one month and also 6% after one year. Among dual users (smokers who were vaping daily at baseline), 22% had stopped smoking after one month and 46% after one year. In dual users who were still smoking at follow up, cigarette consumption decreased by 5.3 cig/day after one month (from 11.3 to 6.0 cig./day, p=0.006), but remained unchanged between baseline and 1-year follow up. CONCLUSIONS: E-cigarettes may contribute to relapse prevention in former smokers and smoking cessation in current smokers. PMID- 24229844 TI - Protective behavioral strategy use and motivations for drinking: exploring Alternatives to Drinking strategies. AB - Protective behavioral strategy (PBS) use is associated with less alcohol consumption and fewer alcohol-related problems. Further, greater endorsement of social or enhancement drinking motives (i.e., positive motives) is associated with less frequent PBS use. Limited research has, however, explored coping or conformity motives (i.e., negative motives) in relation to PBS. Consequently, the present study aimed to (1) identify the types of PBS most strongly associated with negative and positive motives and (2) examine different types of PBS as mediators of the relationship between each drinking motive and alcohol outcomes. Participants were college students (n=303; 70% women) who completed measures of drinking motives, PBS, alcohol use, and alcohol-related problems. Results indicated that greater endorsement of positive drinking motives were more strongly associated with less frequent use of PBS while drinking whereas negative motives were more strongly related to less frequent Alternatives to Drinking strategy use. Further, strategies used while drinking were more relevant in a model of positive drinking motives and Alternatives to Drinking strategies were more relevant in a model of negative motives. These findings may suggest that whereas individuals with stronger positive motives have difficulty using strategies while drinking, individuals who drink to cope or conform have greater difficulty utilizing Alternatives to Drinking strategies. Based on our results demonstrating that different types of PBS are more relevant for various types of drinkers, it may be important for future interventions to discuss not only the participant's PBS use but also their motivations for consuming alcohol. PMID- 24229845 TI - Increased incidence of serotype-1 invasive pneumococcal disease in young female adults in The Netherlands. AB - Analysis of the Dutch national invasive pneumococcal disease (IPD) surveillance data by sex reveals an increase in the incidence of serotype-1 disease in young female adults in The Netherlands after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the national immunization schedule. This has led to an overall increase in IPD in women aged 20-45 years, which was not observed in men of the same age. No other differences in serotype shifts possibly induced by the introduction of PCV7 were observed between the sexes in this age group. Serotype 1 is a naturally fluctuating serotype in Europe and it has been associated with disease in young healthy adults before. It remains uncertain whether or not there is an association between the observed increase in serotype 1 disease in young female adults and the implementation of PCV7 in The Netherlands. PMID- 24229846 TI - Poor marital support associate with anxiety and worries during pregnancy in Greek pregnant women. AB - OBJECTIVE: a wide range of psychosocial variables may influence pregnant women's psychological status. However the association between marital and social support, anxiety and worries during pregnancy is a relatively neglected area of research. Therefore, the aim of this study was to examine the relationship between marital support, social support, antenatal anxiety and pregnancy worries after controlling for the effects of background variables. SETTING: public hospital in Athens, Greece. DESIGN: a cross-sectional study. PARTICIPANTS: 165 pregnant women attending an antenatal clinic for antenatal screening between January 2011 and March 2011. METHODS: anxiety was measured using the State scale of the State Trait Anxiety Inventory, pregnancy worries were measured with the Cambridge Worry Scale, social support with the Social Support Questionnaire-6 and marital satisfaction with the Quality of Marriage Index. Pearson's correlation coefficients were calculated among all study variables, followed by hierarchical multiple linear regression. FINDINGS: a STAI score of >=43 was taken as indicative of anxiety and 44.4% of participants responded with a score of 43 or above. Linear regression analysis showed that conception after IVF treatment and low marital satisfaction were both significantly related to anxiety and pregnancy worries. In addition, low income level was significantly related to pregnancy worry whereas low educational level was related to anxiety. CONCLUSION: the risk factors found in this study could help clinicians target anxiety screening to high-risk populations of pregnant women. Health care professionals and midwives in particular should be trained in the detection and management of anxiety and worries during pregnancy. PMID- 24229847 TI - Efficiency of selection for body weight in a cooperative village breeding program of Menz sheep under smallholder farming system. AB - We evaluated the efficiency of selection for body weight in a cooperative village breeding program for Menz sheep of Ethiopia under smallholder farming system. The design of the program involved organizing villagers in a cooperative breeding group to implement selective breeding of their sheep. The program was jump started through a one-time provision of elite rams from a central nucleus flock, but subsequent replacement rams were selected from within the village flocks. We also evaluated body weight trends in a village where cooperative breeding was not implemented and individual farmers managed their flocks under traditional breeding practices. Under traditional breeding practices, genetic progress over 8 years either stagnated or declined in all the weights recorded. In the cooperative villages, selection differentials of 2.44 and 2.45 kg were achieved in 2010 and 2011 selection seasons, respectively. Birth weight, 3-month weight and 6-month weight increased, respectively, by 0.49, 2.29 and 2.46 kg in the third-generation lambs over the base generation. Improved rams supplied from the central nucleus flock gave an initial genetic lift of 14.4% in the 6-month weight. This was higher than the gain achieved from selection in the village flocks, which was 5.2%. Our results showed that village-based genetic improvement in body weights under smallholder conditions could be feasible if appropriate designs are adopted and that commencing with elite central nucleus rams help jump start village-based programs. PMID- 24229848 TI - Examination of the relationship between theory-driven policies and allowed lost time back claims in workers' compensation: a system dynamics model. AB - OBJECTIVE: The purpose of this study was to develop a model that evaluates the impact of policy changes on the number of workers' compensation lost-time back claims in Ontario, Canada, over a 30-year timeframe. The model was used to test the hypothesis that a theory- and policy-driven model would be sufficient in reproducing historical claims data in a robust manner and that policy changes would have a major impact on modeled data. METHODS: The model was developed using system dynamics methods in the Vensim simulation program. The theoretical effects of policies for compensation benefit levels and experience rating fees were modeled. The model was built and validated using historical claims data from 1980 to 2009. Sensitivity analysis was used to evaluate the modeled data at extreme end points of variable input and timeframes. The degree of predictive value of the modeled data was measured by the coefficient of determination, root mean square error, and Theil's inequality coefficients. RESULTS: Correlation between modeled data and actual data was found to be meaningful (R(2) = 0.934), and the modeled data were stable at extreme end points. Among the effects explored, policy changes were found to be relatively minor drivers of back claims data, accounting for a 13% improvement in error. Simulation results suggested that unemployment, number of no-lost-time claims, number of injuries per worker, and recovery rate from back injuries outside of claims management to be sensitive drivers of back claims data. CONCLUSION: A robust systems-based model was developed and tested for use in future policy research in Ontario's workers' compensation. The study findings suggest that certain areas within and outside the workers' compensation system need to be considered when evaluating and changing policies around back claims. PMID- 24229849 TI - Neural responses of posterior to anterior movement on lumbar vertebrae: a functional magnetic resonance imaging study. AB - OBJECTIVE: The purpose of this study was to develop and test a clinically relevant method to mechanically stimulate lumbar functional spinal units while recording brain activity by means of functional magnetic resonance imaging (MRI). METHODS: Subjects were investigated in the prone position with their face lying on a modified stabilization pillow. To minimize head motion, the pillow was fixed to the MRI headrest, and supporting straps were attached around the shoulders. An experienced manual therapist applied controlled, nonpainful pressure stimuli to 10 healthy subjects at 3 different lumbar vertebrae (L1, L3, and L5). Pressure applied to the thumb was used as a control. The stimulation consisted of posterior to anterior (PA) pressure movement. The therapist followed a randomized stimulation protocol projected onto a screen in the MRI room. Blood oxygenation level-dependent responses were analyzed in relation to the lumbar and the thumb stimulations. The study was conducted by the Chiropractic Department, Faculty of Medicine, University of Zurich, Switzerland. RESULTS: No participant reported any discomfort due to the prone-lying position or use of the pillow. Importantly, PA induced pressure produced only minimal head movements. Stimulation of the lumbar spinous processes revealed bilateral neural responses in medial parts of the postcentral gyrus (S1). Additional activity was observed in the secondary somatosensory cortex (S2), posterior parts of the insular cortex, different parts of the cingulate cortex, and the cerebellum. Thumb stimulations revealed activation only in lateral parts of the contralateral S1. CONCLUSION: The current study demonstrates the feasibility of the application of PA pressure on lumbar spinous processes in an MRI environment. This approach may serve as a promising tool for further investigations regarding neuroplastic changes in chronic low back pain subjects. PMID- 24229850 TI - Translation and validation of Chinese version of the problems in everyday living (PEDL) test in patients with mild cognitive impairment. AB - BACKGROUND: Cognitive impairment places older adults at increased risk of functional decline, injuries, and hospitalization. Assessments to determine whether older persons are still capable of meeting the cognitive challenges of everyday living are crucial to ensure their safe and independent living in the community. The present study aims to translate and validate the Chinese version of the Problems in Everyday Living (PEDL) test for use in Chinese population with mild cognitive impairment (MCI). METHODS: The cultural relevancy and content validity of the Chinese version of PEDL (C-PEDL) was evaluated by a seven-member expert panel. Forty patients with MCI and 40 cognitively healthy participants were recruited to examine the psychometric properties of C-PEDL. RESULTS: Significant differences in the C-PEDL scores were found between the patients with MCI and the cognitively healthy controls in both educated (F = 9.96, p = 0.003) and illiterate (F = 10.43, p = 0.004) populations. The C-PEDL had excellent test retest and inter-rater reliabilities, with intraclass correlation coefficient at 0.95 and 0.99 respectively. The internal consistency of C-PEDL was acceptable with Chronbach's alpha at 0.69. The C-PEDL had moderate correlation with the Mini Mental State Examination (r = 0.45, p = 0.004) and the Category Verbal Fluency Test (r = 0.40, p = 0.012), and a moderate negative Spearman's correlation with the Global Deteriorating Scale (r = -0.42, p = 0.007). CONCLUSIONS: The C-PEDL is a valid and reliable test for assessing the everyday problem-solving ability in Chinese older population with MCI. PMID- 24229851 TI - Cognitive and psychosocial phenotype of young children with neurofibromatosis-1. AB - Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills. PMID- 24229852 TI - Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis. AB - Milk kappa-casein-derived bovine glycomacropeptide (GMP) exerts immunomodulatory effects. It exhibits intestinal anti-inflammatory activity in chemically induced models of colitis. However, to validate its clinical usefulness as a nutraceutical, it is important to assess its effects in a model with a closer pathophysiological connection with human inflammatory bowel disease. Therefore, in the present study, we used the lymphocyte-transfer model of colitis in mice and compared the effects of GMP in this model with those obtained in the dextran sulphate sodium (DSS) model. GMP (15 mg/d) resulted in higher body-weight gain and a reduction of the colonic damage score and myeloperoxidase (MPO) activity in Rag1(-/-) mice with colitis induced by the transfer of naive T cells. The colonic and ileal weight:length ratio was decreased by approximately 25%, albeit non significantly. GMP treatment reduced the percentage of CD4+ interferon (IFN) gamma+ cells in mesenteric lymph nodes (MLN). The basal production of IL-6 by MLN obtained from the GMP-treated mice ex vivo was augmented. However, concanavalin A evoked production was similar. The colonic expression of regenerating islet derived protein 3gamma, S100A8, chemokine (C-X-C motif) ligand 1 and IL-1beta was unaffected by GMP, while that of TNF-alpha and especially IFN-gamma was paradoxically increased. In the DSS model, GMP also reduced the activity of colonic MPO, but it failed to alter weight gain or intestinal weight:length ratio. GMP augmented the production of IL-10 by MLN cells and was neutral towards other cytokines, except exhibiting a trend towards increasing the production of IL-6. The lower effect was attributed to the lack of the effect of GMP on epithelial cells. In conclusion, GMP exerts intestinal anti-inflammatory effects in lymphocyte-driven colitis. PMID- 24229853 TI - Official Proceedings of the 13th Congress of the World Federation for Ultrasound in Medicine and Biology, August 26-29, 2011, Vienna, Austria. PMID- 24230458 TI - Molecular mechanisms of ischemic preconditioning and postconditioning as putative therapeutic targets to reduce tumor survival and malignancy. AB - In tumors intermittent hypoxia has been reported to be more representative than normoxia or continuous exposure to low oxygen concentrations. Intermittent hypoxia is thought to increase tumor resistance against both anti-cancer therapy and the sustained ischemia that randomly occurs because of the dynamic nature of tumor vasculature. Here, we hypothesize that the molecular mechanisms underlying intermittent hypoxia in tumor cells share some triggers, modulators, and end effectors of the intermittent episodes of ischemia and reperfusion that characterize ischemic preconditioning and postconditioning. These are among the most effective maneuvers protecting cells from ischemia-reperfusion injury. If this hypothesis were confirmed, several well-investigated molecular mediators of pre/post-conditioning could be explored as therapeutic targets against tumor malignancy. For examples, drugs that completely block the cardioprotection induced by ischemic preconditioning, such as mitochondrial potassium ATP channel inhibitors or mitochondrial permeability transition pore openers, could be extraordinarily efficient in counteracting the adaptations of tumor cells and cancer stem cells to intermittent hypoxia. As a consequence, this strategy should be effective in blunting tumor capacity to progress toward malignancy and survive in ischemic conditions. PMID- 24230459 TI - Modulation of leukocytic populations of gilthead sea bream (Sparus aurata) by the intestinal parasite Enteromyxum leei (Myxozoa: Myxosporea). AB - SUMMARY The cellular mucosal and systemic effectors of gilthead sea bream (GSB) (Sparus aurata) involved in the acute immune response to the intestinal parasite Enteromyxum leei were studied in fish experimentally infected by the anal route. In the intestinal inflammatory infiltrates and in lymphohaematopoietic organs (head kidney and spleen) of parasitized fish, the number of plasma cells, B cells (IgM immunoreactive) and mast cells (histamine immunoreactive) were significantly higher, whereas the number of acidophilic granulocytes (G7 immunoreactive) decreased, compared with non-parasitized and unexposed fish. These differences were stronger at the posterior intestine, the main target of the parasite, and no differences were found in the thymus. In non-parasitized GSB, the percentage of splenic surface occupied by melanomacrophage centres was significantly higher. These results suggest that the cellular response of GSB to E. leei includes proliferation of leukocytes in lymphohaematopoietic organs and recruitment into intestines via blood circulation involving elements of innate and adaptive immunity. Acidophilic granulocytes and mast cells presented opposite patterns of response to the parasite infection, with an overall depletion of the former and an increased amount of the latter. Some differences between both cell types were also detected in regard to their granule density and cell morphology. PMID- 24230460 TI - Genetic analysis of kinematic traits at the trot in Lusitano horse subpopulations with different types of training. AB - The possibility of using quantitative kinematic traits as indirect selection criteria for sport performance could be beneficial to perform an early genetic evaluation of the animals. The genetic parameters for objectively measured kinematic traits under field conditions have been estimated for the first time, in order to potentially use these traits as indicators of gait quality in future selection of the Lusitano breed. The repeatability within three different types of training (dressage, bullfighting and untrained) was also discussed. A total of 176 males (4 to 14 years old) were recorded at trot in hand using a 3D videographic system. The speed and 10 kinematic traits were studied (one temporal, two linear and seven angular variables). The genetic parameters of the kinematic variables were estimated using VCE software. The heritability estimates were moderate to high (0.18 to 0.53). The stride length and the forelimb angular variables presented the highest heritabilities (0.49 to 0.53), whereas the hindlimb angular variables revealed the lowest values (0.18 to 0.40). More than half of the genetic correlations were moderately to highly positive (mostly 0.20 to 0.70; up to 0.88 between hindlimb traits). The dressage and bullfighting groups presented the highest repeatabilities (over 0.6) in the majority of the traits, maybe because of the acquired gait regularity expected in animals subjected to specific training, and suggesting a greater influence of the individuals over the kinematic traits studied in these two subpopulations than in the untrained subpopulation. The longer swing phase duration and the larger range of motion of the elbow, hock and pelvis joints observed in the dressage group may indicate a better gait quality of this group, according to FEI (International Equestrian Federation) standards. The bullfighting and untrained groups were more similar to each other in terms of kinematic traits. Selection of young horses for characteristics such as stride length and the hindlimbs traits can apparently contribute to further genetic improvement of the performance of Lusitano breed. PMID- 24230461 TI - Feasibility and utility of positive psychology exercises for suicidal inpatients. AB - OBJECTIVE: The objective was to assess the feasibility and acceptability of nine positive psychology exercises delivered to patients hospitalized for suicidal thoughts or behaviors, and to secondarily explore the relative impact of the exercises. METHOD: Participants admitted to a psychiatric unit for suicidal ideation or behavior completed daily positive psychology exercises while hospitalized. Likert-scale ratings of efficacy (optimism, hopelessness, perceived utility) and ease of completion were consolidated and compared across exercises using mixed models accounting for age, missing data and exercise order. Overall effects of exercise on efficacy and ease were also examined using mixed models. RESULTS: Fifty-two (85.3%) of 61 participants completed at least one exercise, and 189/213 (88.7%) assigned exercises were completed. There were overall effects of exercise on efficacy (chi(2)=19.39; P=.013) but not ease of completion (chi(2)=11.64; P=.17), accounting for age, order and skipped exercises. Effect (Cohen's d) of exercise on both optimism and hopelessness was moderate for the majority of exercises. Exercises related to gratitude and personal strengths ranked highest. Both gratitude exercises had efficacy scores that were significantly (P=.001) greater than the lowest-ranked exercise (forgiveness). CONCLUSION: In this exploratory project, positive psychology exercises delivered to suicidal inpatients were feasible and associated with short-term gains in clinically relevant outcomes. PMID- 24230462 TI - Exploitation of deep-sea resources: the urgent need to understand the role of high pressure in the toxicity of chemical pollutants to deep-sea organisms. AB - The advent of industrial activities in the deep sea will inevitably expose deep sea organisms to potentially toxic compounds. Although international regulations require environmental risk assessment prior to exploitation activities, toxicity tests remain focused on shallow-water model species. Moreover, current tests overlook potential synergies that may arise from the interaction of chemicals with natural stressors, such as the high pressures prevailing in the deep sea. As pressure affects chemical reactions and the physiology of marine organisms, it will certainly affect the toxicity of pollutants arising from the exploitation of deep-sea resources. We emphasize the need for environmental risk assessments based on information generated from ecotoxicological trials that mimic, as close as possible, the deep-sea environment, with emphasis to a key environmental factor - high hydrostatic pressure. PMID- 24230463 TI - Role of epicardial adipose tissue in coronary artery disease in non-obese patients. AB - BACKGROUND: Epicardial adipose tissue (EAT) surrounding the heart may contribute to the development of coronary artery disease (CAD) through its local secretion of adipocytokines. Although the quantity of EAT is associated with obesity and metabolic syndrome, the role of EAT in the development of CAD in non-obese patients remains to be determined. METHODS: This study included 41 patients with CAD who underwent coronary artery bypass graft surgery and 28 patients without CAD who underwent other cardiac surgery. EAT volume was measured by 64-slice multi-detector computed tomography before the surgery. We obtained pericardial fluid and epicardial and subcutaneous adipose tissue samples at the surgery. We investigated the relationship between EAT volume and adiponectin levels in pericardial fluid and incident CAD in patients with and without obesity (body mass index>25 kg/m(2)). RESULTS: There was no significant difference in EAT volume between obese patients with and without CAD (55.5 +/- 40.2 mL vs. 40.1 +/- 19.7 mL, p=0.323). However, EAT volume was significantly greater in non-obese patients with CAD compared to those without CAD (35.0 +/- 18.8 mL vs. 15.7 +/- 11.0 mL, p<0.001). Adiponectin concentrations in pericardial fluid were significantly lower in non-obese patients with CAD compared to those without CAD (2.7 +/- 2.0 MUg/mL vs. 4.3 +/- 3.7 MUg/mL, p=0.049), whereas the adiponectin levels were decreased in obese patients regardless of the presence of CAD. Non obese patients with CAD had significantly larger size adipocytes in EAT but not subcutaneous adipose tissue compared to those without CAD. Multiple logistic regression analysis showed that increased EAT volume was independently associated with incident CAD in non-obese patients. CONCLUSION: Increased EAT may play a crucial role in development of CAD through impairment of adiponectin secretion in non-obese patients. PMID- 24230464 TI - Platelet activation and thrombus formation relates to the presence of myocardial inflammation in patients with cardiomyopathy. AB - BACKGROUND: Patients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy. METHODS: A total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p selectin and thrombospondin expression on platelets. RESULTS: The p-selectin (8.46 +/- 3.67 AU) and thrombospondin (26.56 +/- 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r=0.573, p<0.05; thrombospondin: r=0.488, p<0.05) and the endothelial/interstitial activation (p-selectin: r=0.521, p<0.05; thrombospondin: r=0.39, p<0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n=3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 +/- 5.5 AU vs. 8.1 +/- 3.2 AU, p<0.05) and this was associated with elevated myocardial inflammation scores. CONCLUSION: Myocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions. PMID- 24230465 TI - Molecular epidemiology of Staphyloccocus aureus colonization in the Old Order of Amish of Lancaster County, Pennsylvania, USA. AB - Transmission of Staphylococcus aureus colonization in community-based populations is not well understood. We sought to describe the molecular epidemiology of S. aureus colonization in the Old Order Amish. The study was a prospective, observational study of healthy adults and their same-sex siblings who were cultured from the anterior nares twice. S. aureus isolates were characterized using spa typing. Overall, 40% (159/398) of the study population was colonized with S. aureus. There were 84 spa types with the most abundant spa types being t012 (13%) and t021 (7%). There was no clustering of spa types within sibling groups; however, there was clustering within households. There were 111 S. aureus colonized participant pairs living within the same household. Of these, 47% had concordant spa types. The diversity of spa types across a relatively isolated, genetically homogenous population with a similar lifestyle is striking. Taken together this suggests that S. aureus transmission is a local phenomenon limited to very close contact. PMID- 24230466 TI - Special aspects of interleukin-33 and the IL-33 receptor complex. AB - Interleukin-33 (IL-33) is an unconventional member of the IL-1 family: it is a dual function cytokine. Many different cell types, tissue cells and leukocytes, produce IL-33 either constitutively or after stimulation and release it by a poorly defined molecular mechanism. Free IL-33 acts as a classical cytokine by binding to target cells expressing receptors for IL-33 minimally consisting of ST2 and IL-1RAcP. Depending on the target cell type IL-33 will stimulate cell type specific signal transduction mechanisms and thereby change the biosynthetic profile of the respective cell. In addition, it is stored in the nucleus of cells and may be released after cell stress, death by injury or necrosis, acting as an alarmin by orchestrating a sterile inflammation. Furthermore, IL-33 has intracrine functions in the cell producing it, which are independent of IL-33 receptors. Intracellular IL-33 is predominantly found in the nucleus associated to the chromatin and may exert gene regulatory function by yet poorly defined mechanisms. It is the aim of this review to address two basic biological aspects of the IL-33/IL-33 receptor system. First, to summarize the current understanding of the fate and function of intracellular IL-33, and second, to discuss recent advances in the knowledge of the molecular composition, function and regulation of the IL-33 receptor complex, including initial signaling mechanisms. PMID- 24230467 TI - Preface: Sourdough--multifunctional process technology for future food challenges. PMID- 24230468 TI - Enzymatic and bacterial conversions during sourdough fermentation. AB - Enzymatic and microbial conversion of flour components during bread making determines bread quality. Metabolism of sourdough microbiota and the activity of cereal enzymes are interdependent. Acidification, oxygen consumption, and thiols accumulation by microbial metabolism modulate the activity of cereal enzymes. In turn, cereal enzymes provide substrates for bacterial growth. This review highlights the role of cereal enzymes and the metabolism of lactic acid bacteria in conversion of carbohydrates, proteins, phenolic compounds and lipids. Heterofermentative lactic acid bacteria prevailing in wheat and rye sourdoughs preferentially metabolise sucrose and maltose; the latter is released by cereal enzymes during fermentation. Sucrose supports formation of acetate by heterofermentative lactobacilli, and the formation of exopolysaccharides. The release of maltose and glucose by cereal enzymes during fermentation determines the exopolysaccharide yield in sourdough fermentations. Proteolysis is dependent on cereal proteases. Peptidase activities of sourdough lactic acid bacteria determine the accumulation of (bioactive) peptides, amino acids, and amino acid metabolites in dough and bread. Enzymatic conversion and microbial metabolism of phenolic compounds is relevant in sorghum and millet containing high levels of phenolic compounds. The presence of phenolic compounds with antimicrobial activity in sorghum selects for fermentation microbiota that are resistant to the phenolic compounds. PMID- 24230469 TI - Microbial ecology of sourdough fermentations: diverse or uniform? AB - Sourdough is a specific and stressful ecosystem inhabited by yeasts and lactic acid bacteria (LAB), mainly heterofermentative lactobacilli. On the basis of their inocula, three types of sourdough fermentation processes can be distinguished, namely backslopped ones, those initiated with starter cultures, and those initiated with a starter culture followed by backslopping. Typical sourdough LAB species are Lactobacillus fermentum, Lactobacillus paralimentarius, Lactobacillus plantarum, and Lactobacillus sanfranciscensis. Typical sourdough yeast species are Candida humilis, Kazachstania exigua, and Saccharomyces cerevisiae. Whereas region specificity is claimed in the case of artisan backslopped sourdoughs, no clear-cut relationship between a typical sourdough and its associated microbiota can be found, as this is dependent on the sampling, isolation, and identification procedures. Both simple and very complex consortia may occur. Moreover, a series of intrinsic and extrinsic factors may influence the composition of the sourdough microbiota. For instance, an influence of the flour (type, quality status, etc.) and the process parameters (temperature, pH, dough yield, backslopping practices, etc.) occurs. In this way, the presence of Lb. sanfranciscensis during sourdough fermentation depends on specific environmental and technological factors. Also, Triticum durum seems to select for obligately heterofermentative LAB species. Finally, there are indications that the sourdough LAB are of intestinal origin. PMID- 24230470 TI - How the sourdough may affect the functional features of leavened baked goods. AB - Sourdough fermentation is one of the oldest food biotechnologies, which has been studied and recently rediscovered for its effect on the sensory, structural, nutritional and shelf life properties of leavened baked goods. Acidification, proteolysis and activation of a number of enzymes as well as the synthesis of microbial metabolites cause several changes during sourdough fermentation, which affect the dough and baked good matrix, and influence the nutritional/functional quality. Currently, the literature is particularly rich of results, which show how the sourdough fermentation may affect the functional features of leavened baked goods. In the form of pre-treating raw materials, fermentation through sourdough may stabilize or to increase the functional value of bran fractions and wheat germ. Sourdough fermentation may decrease the glycaemic response of baked goods, improve the properties and bioavailability of dietary fibre complex and phytochemicals, and may increase the uptake of minerals. Microbial metabolism during sourdough fermentation may also produce new nutritionally active compounds, such as peptides and amino acid derivatives (e.g., gamma-amino butyric acid) with various functionalities, and potentially prebiotic exo polysaccharides. The wheat flour digested via fungal proteases and selected sourdough lactobacilli has been demonstrated to be probably safe for celiac patients. PMID- 24230471 TI - Starter cultures for cereal based foods. AB - Fermented cereals play a significant role in human nutrition in all parts of the world where cereals grow. These fermentations are started spontaneously or there have been traditional techniques developed in order to keep starter cultures for these processes alive. With the growing impact of industrial microbiology during 20th century this traditional starter culture propagation was replaced often, especially in the dairy industry, by the use of pure, frozen or freeze-dried cultures grown on microbial media. In contrast to the production of ethanol from cereals, in sourdough a pasteurization step before inoculation is avoided due to gelatinization of starch and inactivation of endogenous enzymes. Therefore cultures must be competitive to the relatively high microbial load of the cereal raw materials and well adapted to the specific ecology determined by the kind of cereal and the process conditions. Less adapted cultures could be used, but then the process of back-slopping of cultures is limited. Although cereal fermentations take the biggest volume among fermented foods, only for sourdoughs commercial cultures are available. PMID- 24230472 TI - Evaluation of exopolysaccharide producing Weissella cibaria MG1 strain for the production of sourdough from various flours. AB - This study determined exopolysaccharide (EPS) production by Weissella cibaria MG1 in sourdoughs prepared from gluten-free flours (buckwheat, oat, quinoa and teff), as well as wheat flour. Sourdoughs (SD) were fermented without sucrose, or by replacing 10% flour with sucrose to support EPS production. The amount of EPS depended on the substrate: high amounts of EPS corresponding to low amounts of oligosaccharides were found in buckwheat (4.2 g EPS/kg SD) and quinoa sourdoughs (3.2 g EPS/kg SD); in contrast, no EPS but panose-series oligosaccharides (PSO) were detected in wheat sourdoughs. Organic acid production, carbohydrates and rheological changes during fermentation were compared to the EPS negative control without added sucrose. Corresponding to the higher mineral content of the flours, sourdoughs from quinoa, teff and buckwheat had higher buffering capacity than wheat. Fermentable carbohydrates in buckwheat, teff and quinoa flours promoted W. cibaria growth; indicating why W. cibaria failed to grow in oat sourdoughs. Endogenous proteolytic activity was highest in quinoa flour; alpha-amylase activity was highest in wheat and teff flours. Protein degradation during fermentation was most extensive in quinoa and teff SD reducing protein peaks 18 29, 30-41 and 43-55 kDa extensively. Rheological analyses revealed decreased dough strength (AF) after fermentation, especially in sucrose-supplemented buckwheat sourdoughs correlating with amounts of EPS. High EPS production correlated with high protein, fermentable sugars (glucose, maltose, fructose), and mineral contents in quinoa flour. In conclusion, W. cibaria MG1 is a suitable starter culture for sourdough fermentation of buckwheat, quinoa and teff flour. PMID- 24230473 TI - Sourdough lactic acid bacteria: exploration of non-wheat cereal-based fermentation. AB - Cereal-based foods represent a very important source of biological as well as of cultural diversity, as testified by the wide range of derived fermented products. A trend that is increasingly attracting bakery industries as well as consumers is the use of non-conventional flours for the production of novel products, characterised by peculiar flavour and better nutritional value. Lactic acid bacteria microbiota of several non-wheat cereals and pseudo-cereals has been recently deeply investigated with the aim of studying the biodiversity and finding starter cultures for sourdough fermentation. Currently, the use of ancient or ethnic grains is mainly limited to traditional typical foods and the bread making process is not well standardised with consequent negative effects on the final properties. The challenge in fermenting such grains is represented by the necessity to combine good technology and sensory properties with nutritional/health benefits. The choice of the starter cultures has a critical impact on the final quality of cereal-based products, and strains that dominate and outcompete contaminants should be applied for specific sourdough fermentations. In this sense, screening and characterisation of the lactic acid bacteria microbiota is very useful in the improvement of a peculiar flour, from both a nutritional and technological point of view. PMID- 24230474 TI - Use of fungal proteases and selected sourdough lactic acid bacteria for making wheat bread with an intermediate content of gluten. AB - This study was aimed at combining the highest degradation of gluten during wheat flour fermentation with good structural and sensory features of the related bread. As estimated by R5-ELISA, the degree of degradation of immune reactive gluten was ca. 28%. Two-dimensional electrophoresis and RP-FPLC analyses showed marked variations of the protein fractions compared to the untreated flour. The comparison was also extended to in vitro effect of the peptic/tryptic-digests towards K562 and T84 cells. The flour with the intermediate content of gluten (ICG) was used for bread making, and compared to whole gluten (WG) bread. The chemical, structural and sensory features of the ICG bread approached those of the bread made with WG flour. The protein digestibility of the ICG bread was higher than that from WG flour. Also the nutritional quality, as estimated by different indexes, was the highest for ICG bread. PMID- 24230475 TI - Influence of particle size on bioprocess induced changes on technological functionality of wheat bran. AB - Wheat bran is nutritionally an important source of dietary fibre, vitamins and minerals, but its negative influence on dough rheology, texture and sensory quality of bread limits its use in bread baking. The current study aimed at improving the technological functionality of bran by bioprocessing Wheat bran of different particle size (750, 400, 160, 50 MUm) was fermented 8 h or 24 h with Lactobacillus brevis E95612 and Kazachstania exigua C81116 with or without addition of enzyme mixture with various carbohydrase activities. Kinetics of growth and acidification showed that the growth of the starters was enhanced in the presence of enzymes in bran having particle size of 160 and 50 MUm. Fermentation was critical to improve dough stability and volume of bran enriched breads, whereas addition of enzymes had the most significant effect in improving bread shelf-life. Wheat bread containing 160 MUm bran fermented 8 h with enzymes had mild flavour, the highest volume and shelf-life. Reduction of particle size increased perceived smoothness of mouthfeel but provided darker colour in bran containing breads. The short 8 h bioprocessing, with or without enzymes did not increase pungent flavour or bitter aftertaste in comparison with the native bran. PMID- 24230476 TI - Cereal fungal infection, mycotoxins, and lactic acid bacteria mediated bioprotection: from crop farming to cereal products. AB - Lactic acid bacteria (LAB) metabolites are a reliable alternative for reducing fungal infections pre-/post-harvest with additional advantages for cereal-base products which convene the food market's trend. Grain industrial use is in expansion owing to its applicability in generating functional food. The food market is directed towards functional natural food with clear health benefits for the consumer in detriment to chemical additives. The food market chain is becoming broader and more complex, which presents an ever-growing fungal threat. Toxigenic and spoilage fungi are responsible for numerous diseases and economic losses. Cereal infections may occur in the field or post-processing, along the food chain. Consequently, the investigation of LAB metabolites with antifungal activity has gained prominence in the scientific research community. LAB bioprotection retards the development of fungal diseases in the field and inhibit pathogens and spoilage fungi in food products. In addition to the health safety improvement, LAB metabolites also enhance shelf-life, organoleptic and texture qualities of cereal-base foods. This review presents an overview of the fungal impact through the cereal food chain leading to investigation on LAB antifungal compounds. Applicability of LAB in plant protection and cereal industry is discussed. Specific case studies include Fusarium head blight, malting and baking. PMID- 24230477 TI - [Current issues in hereditary neuropathies]. AB - This short review highlights five studies published in 2012 in the field of Charcot-Marie-Tooth disease (CMT) and transthyretin familial amyloid neuropathies (TTR-FAN). Regarding CMT, an Australian pediatric study shows the high prevalence of impaired speech perception and hearing disability in children with CMT1 or CMT2 with normal or near normal audiometry (Rance et al., 2012). In a second study, the clinical and electrophysiological characteristics of 14 patients with CMT4C due to mutations in SH3TC2 gene are described (Yger et al., 2012). The 3 clinical hallmarks of CMT4C patients in this French cohort are the high prevalence of scoliosis, the proximal motor weakness and the cranial nerves involvement. Concerning TTR-FAN, the first data from French and international registries are reported (Adams et al., 2012; Coelho et al., 2013) and a phase II trial describes the results of taurourodeoxycholic acid and doxycycline treatment (Obici et al., 2012). PMID- 24230478 TI - High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations. AB - Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies. PMID- 24230479 TI - Is critical illness polyneuropathy associated with decreased heart rate variability? AB - INTRODUCTION: This pilot study assessed the association between critical illness polyneuropathy (CIP) and decreased heart rate variability (HRV) in intensive care patients. METHODS: All patients admitted to the intensive care unit and expected to be ventilated for at least 72 hours were included and underwent weekly electromyograms and HRV analyses for three weeks. HRV was assessed by time domain analysis of 24h recording electrocardiograms, and alterations in HRV were assessed as the square root of the mean squared differences of successive RR intervals (RMSSD) <= 15. RESULTS: We evaluated 26 patients, 12 men and 14 women, median age 64 years. During follow-up, 12 patients died and 9 developed CIP. CIP was not associated with age, sex, simplified acute physiology score II and treatment agents. Altered RMSSD tended to be associated with onset of CIP (P=0.06). Altered RMSSD occurred earlier or at the same time as electromyogram abnormalities in all CIP patients, but the difference was not significant. CONCLUSION: Altered HRV, may be associated with the onset of CIP in ICU patients. Although not statistically significant (P=0.06), altered RMSSD may be a surrogate marker of CIP in ICU patients undergoing mechanical ventilation. The physiological pathway linking HRV and CIP remains uncertain. PMID- 24230480 TI - The experiences and needs of children living with a parent with young onset dementia: results from the NeedYD study. AB - BACKGROUND: Children of patients with young onset dementia (YOD) who are confronted with a parent who has a progressive disease, often assist in caregiving tasks, which may have a great impact on their lives. The objective of the present study is to explore the experiences of children living with a young parent with dementia with a specific focus on the children's needs. METHODS: Semi structured interviews with 14 adolescent children between the ages of 15 and 27 years of patients with YOD were analyzed using inductive content analysis. Themes were identified based on the established codes. RESULTS: The emerging categories were divided into three themes that demonstrated the impact of dementia on daily life, different ways of coping with the disease, and children's need for care and support. The children had difficulties managing all of the responsibilities and showed concerns about their future. To deal with these problems, they demonstrated various coping styles, such as avoidant or adaptive coping. Although most children were initially reluctant to seek professional care, several of them expressed the need for practical guidance to address the changing behavior of their parent. The children felt more comfortable talking to someone who was familiar with their situation and who had specific knowledge of YOD and the available services. CONCLUSION: In addition to practical information, more accessible and specific information about the diagnosis and the course of YOD is needed to provide a better understanding of the disease for the children. These findings underline the need for a personal, family-centered approach. PMID- 24230481 TI - Leaf anatomy and histochemistry of three species of Ficus sect. Americanae supported by light and electron microscopy. AB - In this work the leaf anatomy of three species of Ficus section Americanae (Miq.) Miq. from Brazil, whose leaves and latex are used in folk medicine is reported. The work was carried out using light and scanning electron microscopy in order to characterize these species and to evaluate their taxonomic significance, and also contribute to the quality control of their ethnodrugs. The three species (Ficus cyclophylla, Ficus elliotiana, and Ficus caatingae) showed hypostomatic leaves, anomocytic stomata, straight epidermal cell outlines, and a dorsiventral mesophyll. Some micro-morphological characters such as density and distribution of epicuticular waxes, glandular trichomes, the length and width of stomata, as well as the palisade of mesophyll and petiole outlines proved to be the most useful and distinctive characters for the separation of species. These may contribute as additional support for the taxonomy of the section and for the quality control of their ethnodrugs. PMID- 24230482 TI - [Immunotherapy in epithelial ovarian carcinoma: hope and reality]. AB - INTRODUCTION: Epithelial ovarian carcinoma (EOC) has a worst prognosis with little progress in terms of survival for the last two decades. Immunology received little interest in EOC in the past, but now appears very important in the natural history of this cancer. This review is an EOC immunology state of art and focuses on the place of immunotherapy in future. MATERIAL AND METHODS: A systematic review of published studies was performed. Medline baseline interrogation was performed with the following keywords: "Ovarian carinoma, immunotherapy, T-lymphocyte, regulator T-lymphocyte, dendritic cells, macrophage, antigen, chemotherapy, surgery, clinical trials". Identified publications (English or French) were assessed for the understanding of EOC immunology and the place of conventional treatment and immunotherapy strategy. RESULTS: Intratumoral infiltration by immune cells is a strong prognotic factor in EOC. Surgery and chemotherapy in EOC decrease imunosuppression in patients. The antitumoral immunity is a part of the therapeutic action of surgery and chemotherapy. Until now, immunotherapy gave some disappointing results, but the new drugs that target the tolerogenic tumoral microenvironnement rise and give a new hope in the treatment of cancer. CONCLUSION: Immunology controls the EOC natural history. The modulation of immunosuppressive microenvironment associated with the stimulation of antitumoral immunity could be the next revolution in the treatment of cancer. PMID- 24230483 TI - Winter is associated with failure in the alarm treatment of nocturnal enuresis. AB - OBJECTIVE: To assess whether the winter season in Japan is associated with failure in the alarm treatment of nocturnal enuresis (NE). PATIENTS AND METHODS: Consecutive patients with NE referred to our center between June 2009 and May 2010 were treated with the enuresis alarm (EA). The EA was used for 16 weeks with each child. Patients were divided into a success group and a treatment failure group. Pretreatment variables were collected, including age, sex, night-time urine volume, severity of enuresis, presence of nocturnal polyuria, presence of daytime incontinence, and treatment initiation season. These variables and initial success rates were retrospectively compared between the two groups. Chi square, Student t tests, and multivariate regression analysis were used for statistical analysis. RESULTS: A total of 67 children with NE were evaluated, 37 (55%) in the success group and 30 (45%) in the failure group. None of the pretreatment variables differed significantly between groups except for season; winter season initiation was an independent risk factor for failure in multivariate regression analysis. CONCLUSIONS: Winter was associated with failure in the EA treatment. We recommend that EA be introduced in the summer season in Japan to achieve an optimal success rate. PMID- 24230484 TI - Cloacal exstrophy: a single center experience. AB - OBJECTIVE: Cloacal exstrophy is an exceedingly rare and complex anomaly. The records of 23 patients treated in a tertiary care center with limited infrastructure were analyzed for anatomic types, associated anomalies, surgical procedures adopted, and the outcome. MATERIALS AND METHODS: There were 14 males. Seventeen babies were preterm with an average weight of 1.92 kg. The time of presentation, gestational age, birth weight, position of the hemibladders and associated malformations were noted. Reconstruction procedures involved dismantling of the hemibladders and primary turn in, tubularization of the bowel with an end colostomy, and reconstruction of the abdominal wall. Results of the primary surgical repair, bowel function, and outcome of secondary procedures were analyzed. RESULTS: The position of hemibladders was lateral in 11, upper confluent in 4 and lower confluent in 8. Associated anomalies were noted in 19 patients. Four patients presented late (>5 days). Five died preoperatively, all had major associated anomalies. Four of them were preterm with average weight of 1.4 kg. Two patients refused surgery. Single-stage surgical reconstruction was done in 15 patients. Five patients died postoperatively because of associated anomalies, prematurity, and sepsis. One patient is waiting for surgery. Six patients had follow-up at 3-42 months and are awaiting further reconstruction. Four patients were lost to follow-up. CONCLUSIONS: Prematurity, late presentation, and sepsis are the major causes of high mortality noted in this series. In our experience, single-stage reconstruction without osteotomy gives satisfactory results. PMID- 24230485 TI - Genetic correlations between production and disease traits during first lactation in Holstein cows. AB - The aim of this study was to estimate genetic correlations between milk yield, somatic cell score (SCS), mastitis, and claw and leg disorders (CLDs) during first lactation in Holstein cows by using a threshold-linear random regression test-day model. We used daily records of milk, fat and protein yields; somatic cell count (SCC); and mastitis and CLD incidences from 46 771 first-lactation Holstein cows in Hokkaido, Japan, that calved between 2000 and 2009. A threshold animal model for binary records (mastitis and CLDs) and linear animal model for yield traits were applied in our multiple trait analysis. For both liabilities and yield traits, additive genetic effects were used as random regression on cubic Legendre polynomials of days on milk. The highest positive genetic correlations between yields and disease incidences (0.36 for milk and mastitis, 0.56 for fat and mastitis, 0.24 for protein and mastitis, 0.32 for milk and CLD, 0.44 for fat and CLD and 0.31 for protein and CLD) were estimated at about the time of peak milk yield (36 to 65 days in milk). Selection focused on early lactation yield may therefore increase the risk of mastitis and CLDs. The positive genetic correlations of SCS with mastitis or CLD incidence imply that selection to reduce SCS in the early stages of lactation would decrease the incidence of both mastitis and CLD. PMID- 24230486 TI - Psychometric properties and validation of the Reasons for Living Inventory in an outpatient clinical population in Malaysia. AB - The Reasons For Living Inventory has been shown to have good psychometric properties in Western populations for the past three decades. The present study examined the psychometric properties and factor structure of English and Malay version of the Reasons For Living (RFL) Inventory in a sample of clinical outpatients in Malaysia. The RFL is designed to assess an individual's various reasons for not committing suicide. A total of 483 participants (283 with psychiatric illnesses and 200 with non-psychiatric medical illnesses) completed the RFL and other self-report instruments. Results of the EFA (exploratory factor analysis) and CFA (confirmatory factor analysis) supported the fit for the six factor oblique model as the best-fitting model. The internal consistency of the RFL was alpha=.94 and it was found to be high with good concurrent, criterion and discriminative validities. Thus, the RFL is a reliable and valid instrument to measure the various reasons for not committing suicide among psychiatry and medical outpatients in Malaysia. PMID- 24230487 TI - Improving the accuracy of intraoperative perforator location in DIEP flaps. PMID- 24230488 TI - Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. AB - Complex relationships exist between the gut microflora and their human hosts. Emerging evidence suggests that bacterial dysbiosis within the colon may be involved in the pathogenesis of the metabolic syndrome, type 2 diabetes and CVD. The use of dietary prebiotic supplements to restore an optimal balance of intestinal flora may positively affect host metabolism, representing a potential treatment strategy for individuals with cardiometabolic disorders. The present review aimed to examine the current evidence supporting that dietary prebiotic supplementation in adults has beneficial effects on biochemical parameters associated with the development of metabolic abnormalities including obesity, glucose intolerance, dyslipidaemia, hepatic steatosis and low-grade chronic inflammation. Between January 2000 and September 2013, eight computer databases were searched for randomised controlled trials published in English. Human trials were included if at least one group received a dietary prebiotic intervention. In the present review, twenty-six randomised controlled trials involving 831 participants were included. Evidence indicated that dietary prebiotic supplementation increased self-reported feelings of satiety in healthy adults (standardised mean difference -0.57, 95% CI -1.13, -0.01). Prebiotic supplementation also significantly reduced postprandial glucose (-0.76, 95% CI 1.41, -0.12) and insulin (-0.77, 95% CI -1.50, -0.04) concentrations. The effects of dietary prebiotics on total energy intake, body weight, peptide YY and glucagon-like peptide-1 concentrations, gastric emptying times, insulin sensitivity, lipids, inflammatory markers and immune function were contradictory. Dietary prebiotic consumption was found to be associated with subjective improvements in satiety and reductions in postprandial glucose and insulin concentrations. Additional evidence is required before recommending prebiotic supplements to individuals with metabolic abnormalities. Large-scale trials of longer duration evaluating gut microbial growth and activity are required. PMID- 24230489 TI - [Assessment of the appropriateness of STOPP/START criteria in primary health care in Spain by the RAND method]. AB - INTRODUCTION: A new screenings tool called STOPP/START has been formulated to identify potentially inappropriate prescribing in older people. This study aimed to assess the appropriateness of STOPP/START criteria in primary health care (PHC) in Spain. MATERIAL AND METHOD: The RAND Appropriateness Method was used to obtain agreement on STOPP/START criteria with two rounds in Vigo PHC with 582.968 inhabitants (24% >= 65 years). The pharmacotherapy committee of Vigo PHC area was identified as expert panel, with 12 members from different specialties. In the first round, the committee was provided with relevant literature and a questionnaire with STOPP/START criteria to rate their applicability in PHC with a 9-point Likert scale. Then, each of the criteria was classified according to the median scores and the degree of agreement. In the second round, the experts discussed the undecided criteria and suggestions. RESULTS: Most of the criteria were appropriate. We present a new version with the following differences: to remove START E2 "Biphosphonates in patients taking maintenance oral corticosteroid therapy"; to remove START F3 "Antiplatelet therapy in diabetes mellitus with coexisting major cardiovascular risk factors"; to modify STOPP A9, A15, A16, A17 and E5; and START A1 and A2, adding acenocoumarol to all of them because acenocoumarol is the most used anticoagulant in our country and they only refer to warfarin, and to introduce STOPP C6: "Use of proton pump inhibitors without authorized indication". CONCLUSIONS: Criteria STOPP/START are suitable for use PHC but it is necessary to adapt and update them periodically. PMID- 24230490 TI - Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study. AB - INTRODUCTION: Progressive atrophy occurs in brain regions involved in the working memory network along the schizophrenia's course, but without parallel evolution of working memory impairment. We investigated the functional organization inside this network at different stages of the disease. METHODS: Twenty-eight patients with schizophrenia (16 with long disease duration (>60 months) and 12 with short disease duration (<60 months)) and eleven healthy controls underwent structural and functional MRI during an n-back task to determine atrophy and activation patterns. RESULTS: At similar n-back performances and relative to short disease duration patients, long disease duration patients activated more frontal temporal parietal and frontal network during 0-back and 1-back tasks respectively. n-back scores were correlated to atrophy in the frontal-temporal areas. DISCUSSION: Functional reorganization in the working memory network may play a compensatory role during the first ten years of schizophrenia. PMID- 24230915 TI - Sarcocystis species in red deer revisited: with a re-description of two known species as Sarcocystis elongata n. sp. and Sarcocystis truncata n. sp. based on mitochondrial cox1 sequences. AB - In a previous investigation, five Sarcocystis species were described from Norwegian red deer and believed to be conspecific with species occurring in either reindeer or moose based on sarcocyst morphology and nucleotide sequences of the nuclear ribosomal DNA unit. The aim of the present study was to characterize numerous isolates of these sarcocyst types at the mitochondrial cytochrome c oxidase subunit I gene (cox1) in order to corroborate or refute previous species designations of Sarcocystis in red deer. The Sarcocystis tarandi and Sarcocystis rangiferi-like taxa in red deer and reindeer, respectively, were thoroughly compared by sequencing 14-27 isolates of each type. Sequence comparisons revealed four distinct sequence types, which by phylogenetic analyses were placed in four monophyletic groups according to host origin, and they were therefore considered to represent four separate species. The two taxa of this type in red deer were named Sarcocystis elongata and Sarcocystis truncata, respectively. Sequencing of many isolates of Sarcocystis hjorti and Sarcocystis ovalis from red deer and moose confirmed that these species occur in both hosts. A revised description of the two new species is given and the current knowledge concerning all six Sarcocystis species in red deer is reviewed. PMID- 24230916 TI - The CBCL dysregulated profile: an indicator of pediatric bipolar disorder or of psychopathology severity? AB - BACKGROUND: To evaluate whether the Child Behavior Checklist Dysregulated Profile (CBCL-DP) can be used as an effective predictor of psychopathological severity as indicated by suicidality and comorbidities, as well as a predictor of pediatric bipolar disorder (PBD). METHOD: CBCL-DP scores for 397 youths seeking treatment for mood disorders were calculated by summing the t-scores of the Anxious/Depressed, Aggressive Behaviors, and Attention Problems subscales such that a clinical cut-off of 210 was used to indicate the presence of a dysregulated profile. Suicidality and an increased number of diagnoses were used as markers of illness severity. RESULTS: Those with a dysregulated profile presented more severe suicidal ideation when compared to those without the profile. They also had a significantly larger number of Axis I diagnoses. Groups did not differ in the amount of individuals diagnosed with PBD. LIMITATIONS: Suicidal ideation was assessed by a third-party informant and not from the youths themselves. No other forms of suicidal behavior such as self-harm or suicide attempt were measured. Also there may not be complete convergence between parental reports on behavior and youth reports, which might have affected the results. CONCLUSIONS: These findings suggest that the CBCL-DP is an effective indicator of psychopathological severity through its association with more comorbidities and more severe suicidality. Earlier detection of psychopathological severity through an initial screening tool could aid clinicians in planning treatment and providing quicker and more structured care based on the client's needs. PMID- 24230917 TI - Validation of the Russian version of the Hypomania Checklist (HCL-32) for the detection of Bipolar II disorder in patients with a current diagnosis of recurrent depression. AB - BACKGROUND: There are no validated screening tools for Bipolar Disorder (BD) in Russia. OBJECTIVE: To validate the Russian version of the HCL-32 for the detection of Bipolar II disorder (BD II) in patients with Recurrent Depressive Disorder (RDD). METHODS: 409 patients with a current diagnosis of RDD were recruited. The diagnosis was confirmed by the validated Russian version of the Mini International Neuropsychiatric Interview (MINI). Another investigator interviewed the patients using the NSL-32 questions. RESULTS: The total HCL-32 score in patients with BD II was significantly higher than in patients with RDD: 18.2 (4.22) versus 10.85 (5.81) (p<0.001, d=1447). At the cut-off 14 points the sensitivity was 83.7%, specificity 71.9% (p<0.001). The Cronbach's alpha was 0.887 that means good internal consistency. The best discrimination was achieved with 8 items: decreased need for sleep, less shyness or inhibition, talkativeness, more jokes and puns, jumping thoughts distractibility, exhausting or irritating others and high and more optimistic mood. We proposed the reduced variant of the scale, that includes only these 8 variables, with sensitivity 90.5%, specificity 69.8% (AUC=0.88). CONCLUSIONS: The Russian version of the HCL 32 displayed a good ratio of sensitivity to specificity and can be recommended as a validated screening instrument. An 8-item version of HCL needs further research. LIMITATIONS: Limitations include the specific nature of the sample, the HCL-32 assessment carried out by a psychiatrist, no comparison with other BD screening scales. The results of the 8-item version may be sample and culture dependent. PMID- 24230918 TI - Get in the spirit with SPIRIT 2013: protocol content guideline for clinical trials. PMID- 24230919 TI - Perceived self-efficacy during an emergency situation reduces posttraumatic stress symptoms. AB - This study investigates if perceived self-efficacy during an emergency situation has a protective role in the development of posttraumatic stress symptoms among Italian and Spanish survivors of several emergency situations. We explored the impact of self-efficacy in a multiple regression model including other predictors of posttraumatic stress symptoms, such as emergency prevention knowledge; trust in emergency services; risk perception of becoming a victim of an emergency situation; and conscious and active behaviors in comparison with no conscious and no active behavior during the emergency. We carried out a retrospective study recruiting 214 participants who reported their experience as victims of one specific emergency event. Results showed that survivors who perceived themselves as more self-efficacious during the traumatic event had less posttraumatic stress symptoms. In contrast, female gender, more self-threat perception and higher trauma severity were associated with more symptoms. Findings contribute to better understand human behavior in emergency situations and evidence the protective role of perceived self-efficacy beliefs among survivors of emergency situations. PMID- 24230920 TI - Family relations, stressful events and internalizing symptoms in adolescence: a longitudinal study. AB - This study aimed to examine how emotional and behavioral problems of parents and children and the characteristics of family relationships can be predictors of internalizing symptoms manifested by children after one year. This was a quantitative research study, of the longitudinal type, with a one year interval between the first and second evaluation. Participants were 139 adolescents, and their parents, with ages ranged from 11 to 16 years (M age = 12.90, SD = 1.07). The instruments used were: a Socio-Demographic Data Sheet, Youth Self-Report of 11 to 18 years old (YSR), Adult Self-Report of 18 to 59 years old (ASR), Familiogram (FG), the Family Climate Inventory (FCI) and Inventory of Stressful Events in Adolescence (ISEA). Results indicated that family relationships did not have a significant explanatory power in relation to internalizing symptoms of the adolescent after a year. Based on this study, it is possible to think that during adolescence, the power of the family to influence becomes more restricted in comparison with social and peer influence. PMID- 24230921 TI - Positive and negative affect schedule: psychometric properties for the Brazilian Portuguese version. AB - This study is about the validity and item analysis for the Positive and Negative Affect Schedule (PANAS), respectively through the Exploratory Factor Analysis (principal components method) and the Partial Credit Model (PCM). The scale has been largely used in areas ranging from clinical to social psychology since its release in 1988 by Watson, Clark, and Tellegen. In order to assess validity and item properties (Item Response Theory paradigm), this is study administered PANAS to 354 respondents, 115 male and 239 female subjects, with an average age of 29.5 (SD = 10,18). The results show PANAS's excellent psychometric properties, with consistent dimensions and reliable item functioning, considering the Rasch measurement paradigm expressed in the PCM as an Item Response Theory model for polytomous data. The study considers important cultural issues and the results support more cautious translations for scales as well as further studies concerned with cross-cultural differences on the perception of affect states. PMID- 24230922 TI - Spanish version of the eating attitudes test 40: dimensionality, reliability, convergent and criterion validity. AB - The Eating Attitudes Test-40 (EAT-40; Garner & Garfinkel, 1979) is one of the most widely used measures in the field of eating disorders (ED). The factor structure of the EAT-40, as well as the optimal cut-off score to identify subjects with ED, are subjects of debate. Both controversial issues are addressed in the present study. Participants were 95 clinical females meeting DSM-IV-R criteria for ED and 89 females without ED. The results supported a unidimensional structure of the EAT-40 items scores. The general factor accounted for a high percentage (50.63%) of the variance in EAT-40 total scores. The questionnaire proved to have good internal consistency and test-retest reliability. Clinical participants displayed higher mean scores than normal subjects in the EAT-40. Further, participants meeting DSM-IV-R criteria for ED differed significantly from "symptomatic" and "asymptomatic" participants. Correlations with the BULIT-R and the EDI-II scores supported the convergent validity of the questionnaire. The EAT-40 also demonstrated good specificity (94.38%) and sensitivity (93.68%) to detect ED when a cut-off score of 27 was used to discriminate between subjects with and without ED. The implications of these findings for the conceptualization and the assessment of ED are discussed. PMID- 24230923 TI - Normative data for a Spanish version of the Rey auditory-verbal learning test in older people. AB - The Rey Auditory-Verbal Learning Test is an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology. The purpose of this study was to provide normative data for an elderly population living in Spain. The sample of this study was comprised of 156 volunteers over 60 years of age, which were grouped into six different age groups. These groups comprised of 10 participants between the ages of 61 and 65 in the first group, 23 participants (66-70) in the second, 28 participants (71 75) in the third, 35 participants (76-80) in the fourth, 32 participants (81 85)in the fifth and 28 participants (86-95) in the sixth group. Demographic data were collected and means, deviations, and ranges of all the measures were evaluated. Normative data were calculated from the percentiles, and then converted into age-corrected scaled scores with a mean of 10 and a standard deviation of 3. PMID- 24230924 TI - Romantic attachment in Chilean adults: development of a short-form version of the experiences in close relationships. AB - Though the study of romantic attachment has expanded into all areas of psychology, it remains the case that there is no valid, reliable test available to measure it in Latin America. The present research objective was to adapt a Chilean version of the Experiences in Close Relationships (ECR; Brennan, Clark, & Shaver 1998) questionnaire, developing a short-form version, and to determine its factor structure in two samples of Chilean adults of different ages. A pool of 25 items was chosen to capture the two dimensions (Anxiety and Avoidance), which were obtained through principal components analysis in a sample of 477 adults. Subsequently, the short-form ECR's two-dimensional structure was confirmed using confirmatory factor analysis in a new sample (N = 296). All sub-dimensions' internal consistencies were found to be satisfactory. Evidence for the test's concurrent validity with the variables age, gender, and socioeconomic status was also obtained. The dimensions of romantic attachment showed no differences according to age or gender. However, participants of high socioeconomic status exhibited lower levels of anxious attachment than those with low socioeconomic status. It was concluded that the Chilean short-form version of the ECR has good psychometric properties and is a suitable assessment of adult attachment. PMID- 24230925 TI - The influence of leadership style on subordinates' attachment to the leader. AB - The aim of this research is to explore the extent to which employees establish attachment bonds with their leaders and the effects these bonds have on organizational outcomes. A sample of 225 participants reported on their supervisor's leadership style (transformational, transactional, or passive avoidant), their attachment bonds to this supervisor (anxious or avoidant), and four organizational variables (subordinate's satisfaction, identification with the organization, extra effort, and perceived leadership effectiveness). Results, analyzed using a Partial Least Squares (PLS) approach, indicated that (a) transformational leadership was negatively associated with employees' insecure (anxious or avoidant) attachment to their leader; (b) passive/avoidant leadership was positively associated with subordinates' insecure attachment to their leader; (c) transactional leadership was positively associated with employee's anxious attachment but not with their avoidant attachment; (d) avoidant, but not anxious, attachment to the leader was negatively associated with employee satisfaction, perceived leader effectiveness, employee's extra effort, and organizational identification. PMID- 24230926 TI - Prevalence of oppositional defiant disorder in a sample of Spanish schoolchildren. AB - The aim of this study is to determine the prevalence rate of ODD in school age children, and analyze the variability of the prevalence rates per informant, according to the sources of information, sex, age, and level of agreement between teachers and parents. This is an epidemiological study conducted using a community sample extracted by means of multi-stage stratified sampling. The sample consisted of 1,295 children of both sexes from 6 to 8 years old. For diagnostic evaluation, the Oppositional Defiant Disorder Rating Scale (ODDRS-IV) was used. The estimated global prevalence of ODD, detected by all sources is 16.1%. But if we consider the percentage of subjects detected by only one informant, the prevalence rate is 9.5%. The prevalence according to teachers is 5.1% (95% CI = 3.88-6.31), according to fathers is 9% (95% CI = 7.38-10.54), and according to mothers is 9.7% (95% CI = 8.02-11.29). Teachers report more boys with ODD than girls. Results support the idea of high variability in ODD prevalence rates. Our findings suggest that parents are more prone to detect the disorder than teachers, and that boys present ODD more frequently than girls, only when they are evaluated by their teachers. PMID- 24230927 TI - Depression and neighborhood violence among children and early adolescents in Medellin, Colombia. AB - Violence is considered one of the most important public health problems among Latino countries. In Colombia, approximately 41% of Medellin's inhabitants have witnessed a homicide, 75% have witnessed an aggressive incident, and 40% have been victims of other types of violent incidents. Despite increased national/international attention paid to the effects of neighborhood violence exposure on childhood depression, little is still known about this phenomenon in non-clinical samples. This study examined neighborhood violence exposure and depression (negative mood, interpersonal problems, ineffectiveness, anhedonia, and negative self-esteem) among N = 320 8-12 years old youth. Data were collected from public schools in Medellin during 2009. Kovacs' Children's Depression Inventory was used to assess depression; neighborhood violence exposure was measured using Medellin's Human Rights report on high-low violence rates neighborhoods where participants lived and/or attended school. Results show that 26 children reported depressive symptoms (a prevalence of 8.9 % in the total sample). Among early adolescents (boys and girls), exposure to higher levels of violence was associated with greater ineffectiveness. Gender did not moderate the relationship between violence exposure and depression subscales. Results raise awareness about the importance to further exploring other factors related to neighborhood violence exposure and depression (e.g., developmental stage, gender). PMID- 24230928 TI - Incidental encoding of the serial order of visual-spatial events in working memory. AB - We investigated the incidental encoding in working memory of event serial order in tasks in which the relevant dimension was visual appearance, spatial location, or visual-spatial conjunction. The participants (n = 60) were asked whether two sequences were identical based on the relevant dimension, and to ignore changes in the irrelevant dimension, that is the order of events. Changes in serial order impaired the performance when sequences were identical; this effect was more pronounced in spatial sequences. It is suggested that the order was incidentally encoded with the relevant information to the task in an earlier stage in the information processing, which explains a different pattern of serial order effect according to the relevant dimension. Although encoded, the serial order may not have affected the visual storage in working memory because it might have been kept in a distinct subcomponent rather than the one that stores the visual characteristic. Moreover, the order may have affected spatial storage because the maintenance of this dimension might be related to a rehearsal mechanism based on serial order of sequence. This conclusion qualifies models that admit the architecture of working memory based on the specificity of encoding and functional interaction between subcomponents of storage. PMID- 24230929 TI - Adaptation of the questionnaire of Hahn, Cella, Bode, and Hanrahan in Spanish patients affected by asbestos poisoning. AB - The purpose of this study was to assess whether or not the questionnaire developed by Hahn, Cella, Bode, and Hanharan (2010) for use with cancer patients accurately measures the social well-being of individuals suffering from chronic illnesses associated with asbestos poisoning. One hundred ten male patients with asbestos poisoning were age-matched in blocks to a comparison group of 70 "healthy" controls, all of whom were current or retired employees of the largest naval company in Spain. The results indicate very high reliability of the Hahn et al. (2010) test to assess social well-being in these chronically ill patients, and a high concurrent validity of the measured outcomes with regard to results of the SCL-90 Derogatis questionnaire, especially on the social well-being dimensions of negative emotional support, negative social companionship, and satisfaction. Limitations of the study and possible future directions are discussed. PMID- 24230930 TI - Psychometric properties of the Turkish version of the Composite Scale of Morningness. AB - The Composite Scale of Morningness is widely used and translated into several languages. The aim of the study was to present psychometric properties of Turkish version of CSM based on a sample of high school and university students. A total of 543 high school and 650 university students have participated in to the study. The internal consistency coefficient was found to be .73 (high school) and .80 (university). The test-retest reliability of the scale was .89 in high school sample and .84 in university sample. The mean CMS scores did not differ by gender in both samples. Exploratory and confirmatory factor analysis revealed that the scale is valid. As an external validation, morningness was associated with MEQ scores, sleep length, mid-point of sleep, rising and retiring time. The data obtained in the study suggested that the Turkish version of the CSM is a reliable and valid instrument to assess circadian preference in both high school and university samples. PMID- 24230931 TI - Using learning potential to evaluate children with specific language impairment. AB - This article presents research on a learning potential assessment that was administered to 32 preschool children with typical development, and 32 with specific language impairment receiving treatment at CADIT: the Children's Center for Early Intervention and Development. The study's main objective was to examine whether the language-impaired group's cognitive profile could improve by applying learning potential methodology. Its second aim was to demonstrate the effectiveness of mediation in both groups. The results revealed significant differences between the two groups at pretest on most subscales. As for the second objective, we observed differences between pretest and posttest scores in both groups. In the second group, all differences were significant except in the case of classification and auditory memory, while in the first group, the differences between pretest and posttest scores were significant on all sub scales but visual memory. PMID- 24230932 TI - Perceptions of the self and most people's reactions towards innocent and noninnocent victims. AB - Research has shown that: individuals positively distinguish themselves from most other people; being consistent is positively valued; injunctive and descriptive norms are perceived to protect victims. Joining these findings, we argue that individuals present themselves as following injunctive and descriptive norms towards victims to a higher extent and more consistently than most people. In an experimental study 273 university students of both sexes indicated what they and most other people would approve of (injunctive norm) or typically do (descriptive norm) regarding various reactions towards either an innocent or a noninnocent victim. The reactions involved secondary victimization (devaluation/derogation, avoidance, suffering minimization, blaming the victim) and non secondary victimization (valuation, contact, suffering acknowledgment, not blaming the victim). Participants perceived themselves and most people as approving of more non secondary than secondary victimization reactions, except for blaming the noninnocent victim. Participants indicated they approved of most of the normative reactions to a higher extent than most people, which is interpreted as a new instance of the Primus Inter Pares effect. Participants also indicated they would show more consistency between their injunctive and descriptive norms, especially towards the innocent victim. Results suggest that individuals perceive themselves as more immune to perverse norms than most people. PMID- 24230933 TI - Representations and antinomies: rural and city social objects in a Brazilian peasant community. AB - The present work is part of a series of studies that primarily focus on social representations of rural and city objects in the process of constructing a social identity of the countryside. Using social representation theory, this study aimed to investigate the representational field linked to the rural and city objects for the members of a peasant community. A total of 200 members of a Brazilian rural community from four generational groups, of both sexes and aged between 7 and 81 years, participated in this study. We conducted individual interviews with semi-structured scripts. The data corpora, processed using EVOC software, consisted of free associations of the rural and city inductor terms. In constitutive terms, the results allow for the identification of antinomies between the objects discussed; in functional terms, they indicate that the process of constructing social identity is based on the symbolic field, which acts as a reference system for the preparation of the rural identity shared by the participants. PMID- 24230934 TI - Loneliness of homosexual male students: parental bonding attitude as a moderating factor. AB - The purpose of this paper was to examine the relationships of homosexual male students at the senior high school level and their loneliness using parental bonding attitude as a moderating factor. An amount of 127 homosexual male senior high school students in Taiwan is studied. The Pearson correlation analysis and the hierarchical regression analysis are adapted to examine two proposed hypotheses. Based on the results, homosexual male senior high school students in both hyper-masculine and feminine gender roles are found to feel loneliness, but levels of loneliness of those who possess hyper-masculine gender role are relatively lower than those in a feminine role. In addition, the levels of loneliness of homosexual male senior high school students could be negatively affected by parental bonding attitudes (Care). Recommendations and suggestions for parents as well as teachers of homosexual senior high school male students and future studies are underscored at the end of this article. PMID- 24230935 TI - Zung scale factor invariance in male coronary patients and healthy people. AB - The objective of this study was, firstly, to determine the factor structure and factor invariance of the Zung Self-Rating Depression Scale (ZSDS) and, secondly, to justify its use in coronary patients (CPs) and healthy people (HP). Two comparable samples of males were studied: 217 CPs and 191 HP. Exploratory and confirmatory factor analyses (EFA and CFA) for ordinal data were carried out with Mplus. Two models obtained from all participants in this study and another two, the model of Shafer (2006) from a meta-analysis and that of Barefoot et al. (2000) with CPs, were analyzed in CFA. A two-factor structure was supported by EFA in both samples, but none of the models showed adequate goodness-of-fit for the CPs and the HP in CFA. Only the two and three-factor models obtained from the combined sample of CPs and HP showed adequate goodness-of-fit for HP. The ZSDS showed good reliability, replicated the prevalence of depressive symptoms found in other studies and was able to distinguish between CPs and HP. We conclude that the best fit is obtained from the two-factor solution in HP, that the factor structure of the ZSDS is not invariant and is linked to positively and negatively worded items. PMID- 24230936 TI - Explaining social discrimination: racism in Brazil and xenophobia in Spain. AB - The present study investigates the arguments used by university students in order to explain social differences between social minorities and majorities. In Brazil, the issues investigated refer to White and Black people. In Spain, the reference is to native Spaniards and Moroccan immigrants. The participants were 144 Brazilians and 93 Spaniards, who answered a questionnaire composed of socio demographic variables and one open question about the causes of social inequalities between Black and White people in Brazil and between autochthonous Spaniards and Moroccan Immigrants. A model is proposed to integrate the four discursive classes found using ALCESTE software. In Brazil, the strongest argument is based on the historical roots of the exploitation of Black people. In Spain, cultural differences are the main explanation for social inequalities. PMID- 24230937 TI - Verification of ingroup identity as a longitudinal mediator between intergroup contact and outgroup evaluation. AB - Almost six decades of research have consistently demonstrated that intergroup contact is one of the most powerful ways of improving intergroup attitudes. At least two important limitations, however, still compel researchers to continue work in this area: the issue of long-term effects of contact, and the processes underlying such effects. This report makes a theoretical and empirical contribution with regard to these two aspects introducing a new mediator of the effects of contact: verification of qualities of typical ingroup members that may or may not characterize individual group members (e.g. verification of ingroup identities). One hundred and forty-two high school students participated in a two wave longitudinal study with 12 weeks' lag in Spain. Cross-sectional and longitudinal mediational analyses using multiple imputation data showed that intergroup contact improves general outgroup evaluation through increasing verification of ingroup identities. This research demonstrates the relevance of considering verification of ingroup identity as a mediator for the positive effects of intergroup contact. PMID- 24230938 TI - Autonomy, coping strategies and psychological well-being in young professional tennis players. AB - This research aimed to analyze the role of Psychological Well-being factors in young professional tennis players, assigning special attention to their preferred coping strategies and perceived autonomy that specifically contribute to Psychological Well-being. The conceptual framework utilized for this study was Ryff's Psychological Well-being multidimensional model in order to focus our understanding towards how environment demands of professional sport affect athletes Psychological Well-being. Participants were 155 male professional tennis players with a mean age of 14.61 (SD = 1.86) engaged in South American Tennis Federation tournaments. Instruments utilized were Psychological Well Being Scale EBP, Diaz et al., 2006, Sport Coping Approach Questionnary Spanish version, ACSQ 1 (Kim, Duda, Tomas, & Balaguer, 2003) and Sport Perceived Autonomy Scale, Spanish version (Balaguer, Castillo, & Duda, 2008). Our research revealed that the greater autonomy young athletes perceive while being engaged in professional sport was because of the coping strategies they utilized such as active planning, cognitive restructuring, emotional calmness and seeking of social support. Results confirmed also that the greater perceived autonomy was explaining athletes high levels of Psychological Well-being. PMID- 24230939 TI - Protective factors for adolescent violence against authority. AB - Both the family and school environments influence adolescents' violence, but there is little research focusing simultaneously on the two contexts. This study analyzed the role of positive family and classroom environments as protective factors for adolescents' violence against authority (parent abuse and teacher abuse) and the relations between antisocial behavior and child-to-parent violence or student-to-teacher violence. The sample comprised 687 Spanish students aged 12 16 years, who responded to the Family Environment Scale (FES) and the Classroom Environment Scale (CES). Structural Equation Modeling was used to test our model of violent behavior towards authority based on Catalano and Hawkins' Social Developmental Model (1996). Perceived family cohesion and organization showed an inverse association with parent abuse, suggesting that a positive family environment was a protective factor for the development of violence against parents. Family and classroom environments had direct effects on adolescents' violence against authority, and antisocial behavior showed a mediating effect in this relationship. The model accounted for 81% of the variance in violence against authority. As family environment was a better predictor of violence against authority than school environment, intervention efforts to reduce rates of adolescent violence should focus on helping parents to increase family cohesion and to manage conflictive relationships with their children. PMID- 24230940 TI - Less time, better quality. Shortening questionnaires to assess team environment and goal orientation. AB - When assessing team environments in youth sport, participants often spend substantial time responding to lots of items in questionnaires, causing a lack of efficiency (i.e. time and effort) and a decrease of data quality. The purpose of this work was to create short-forms of the questionnaires PeerMCYSQ, SCQPeer, TEOSQ, and also to analyse the existing short-form of the SCQCoach. In Study 1 we developed the short-forms of the instruments. We shortened the questionnaires by using both theory driven and data-driven criteria. In Study 2, we used also qualitative and quantitative data with the aim of validating the short-forms. Finally, in Study 3 we tested the last version of the short-forms and sought evidences concerning their criterion validity. The results showed evidence that supports the psychometric merit of these short-forms: (a) significantly less missing values were obtained; (b) all the factors obtained alpha values above .70; (c) confirmatory factor analyses demonstrated that the short-forms fitted the hypothesized models well; (d) correlations between variables were coherent with expectations, and (e) structural equation modeling results showed significant paths consistent with previous literature. On average, our participants only spent a third of the time used to complete the original questionnaires. PMID- 24230941 TI - Associations between psychosocial problems and personality disorders among Egyptian adolescents. AB - The study investigated the relationship between psychosocial problems and personality disorders among a sample of 817 Egyptian adolescents (408 males and 409 females). Using 15 subscales from the Adolescent Psychopathology Scale (APS long form) we assessed prevalence rates of a number of internalizing and externalizing psychosocial disorders. Additionally, we investigated whether there are gender differences in psychopathology among Egyptian adolescents and to what extent can psychosocial problems predict specific personality disorders. Stepwise multiple regression analyses showed that the participants experienced higher levels of PD, AV, and BD. Gender differences were found in certain personality disorders as well as in externalizing and internalizing psychosocial problems. A number of externalizing and internalizing psychosocial problems were highly predictive of specific personality disorders. PMID- 24230942 TI - Mindful attention and awareness: relationships with psychopathology and emotion regulation. AB - The growing interest in mindfulness from the scientific community has originated several self-report measures of this psychological construct. The Mindful Attention and Awareness Scale (MAAS) is a self-report measure of mindfulness at a trait-level. This paper aims at exploring MAAS psychometric characteristics and validating it for the Portuguese population. The first two studies replicate some of the original author's statistical procedures in two different samples from the Portuguese general community population, in particular confirmatory factor analyses. Results from both analyses confirmed the scale single-factor structure and indicated a very good reliability. Moreover, cross-validation statistics showed that this single-factor structure is valid for different respondents from the general community population. In the third study the Portuguese version of the MAAS was found to have good convergent and discriminant validities. Overall the findings support the psychometric validity of the Portuguese version of MAAS and suggest this is a reliable self-report measure of trait-mindfulness, a central construct in Clinical Psychology research and intervention fields. PMID- 24230943 TI - Memory for radio advertisements: the effect of program and typicality. AB - We examined the influence of the type of radio program on the memory for radio advertisements. We also investigated the role in memory of the typicality (high or low) of the elements of the products advertised. Participants listened to three types of programs (interesting, boring, enjoyable) with two advertisements embedded in each. After completing a filler task, the participants performed a true/false recognition test. Hits and false alarm rates were higher for the interesting and enjoyable programs than for the boring one. There were also more hits and false alarms for the high-typicality elements. The response criterion for the advertisements embedded in the boring program was stricter than for the advertisements in other types of programs. We conclude that the type of program in which an advertisement is inserted and the nature of the elements of the advertisement affect both the number of hits and false alarms and the response criterion, but not the accuracy of the memory. PMID- 24230944 TI - The importance of supporting adolescents' autonomy in promoting physical-sport exercise. AB - This study was conducted toward the objective of analyzing certain factors that influence physical activity in Spanish adolescent students using self determination theory (Deci & Ryan, 1985; 2000) as a framework. Participants included 698 physical education students whose perception of the autonomy support provided by their teachers was assessed in and out of the class context. Also assessed were social goals of responsibility and relationship with others, basic psychological needs, and intrinsic motivation, which is part of self determination theory (SDT). Finally, the "intention" factor posited by the theory of planned behavior (TPB) and students' rate of exercise in the last twelve months were considered. The results of structural equations modeling suggest autonomy education, autonomy support, and social goals positively predicted certain psychological mediators, which in turn positively predicted students' intrinsic motivation, which was a positive predictor of intention, and that of rate of exercise. The results also highlight the benefit of promoting autonomy to enhance students' physical exercise practice. PMID- 24230945 TI - Satisfaction with life scale in a representative sample of Spanish adults: validation and normative data. AB - The Satisfaction with Life Scale (SWLS) is a measure widely used to assess life satisfaction. This paper aims to test its psychometric properties, factor structure, and distribution scores across age, gender, education, and employment status. For this purpose, a representative sample of the Spanish population (N = 2,964) was used. Although analyses showed no significant differences across age or gender, participants with higher education level and those who held an occupation were more satisfied with their lives. Confirmatory factor analysis revealed a unifactorial structure with significant correlations between the SWLS, and subjective happiness and social support. The internal consistency of the scale was .88. Thus, our results indicate that the Spanish version of the SWLS is a valid and reliable measure of life satisfaction within the Spanish context. PMID- 24230946 TI - Leader-member exchange (LMX) and innovation climate: the role of LMX differentiation. AB - Leader-member Exchange (LMX) theory has been shown to be one of the most compelling theories for understanding the effects of leadership on organizational behavior. This theory proposes that leaders establish differentiated relationships with each of their subordinates according to the exchanges produced between them. Recently, the concept of LMX differentiation has been introduced into the theory to extend research from the dyadic to the group level. The present paper uses a longitudinal design to analyze the moderator role of LMX differentiation in the relationship between mean LMX and innovation climate in a sample of 24 healthcare teams. The results showed no direct effects of mean LMX on changes in innovation climate over time. However, they provide support for the moderator effect of LMX differentiation in this relationship, as it was stronger when LMX differentiation was low than when it was high. PMID- 24230947 TI - Reappraisal of threat value: loss of blocking in human aversive conditioning. AB - Non-specificity of fear is a core aspect of what makes anxiety disorders so impairing: Fear does not remain specific to a single stimulus paired with danger, but generalizes to a broad set of stimuli, resulting in a snowballing of threat signals. The blocking procedure can provide a valuable laboratory model for gaining insight into such threat appraisal and generalization processes. We report two experiments in which we induced selective threat appraisal by using a blocking procedure in human aversive conditioning. We subsequently assessed to what extent such selective threat appraisal is sensitive to different kinds of interference. Results illustrate that the maintenance of selective threat appraisal is not guaranteed: Stimuli present during an aversive conditioning event that are initially tagged with a low threat value, can come to be tagged with a higher threat value later on, without additional experience with these stimuli. We argue that such interference in selective threat appraisal might be one of the mechanisms underlying the pathogenesis of non-specific fear. PMID- 24230948 TI - Millon clinical multiaxial inventory III (MCMI-III) and communication styles in a sample of university students. AB - Despite the controversy generated by the conceptualization of personality disorders, it is well established that the inflexibility of coping styles and dysfunctional behaviors associated with them can lead to a considerable impairment in interpersonal relationships. Although communication is one of the most important processes in relating to others, few empirical studies have been undertaken on the influence of dysfunctional personality patterns on communication styles, which is the main objective of the present cross-sectional study. A total of 529 Spanish university students were assessed using the Millon Clinical Multiaxial Inventory III (MCMI-III), Millon, Davis, and Millon, 1997, and the Communicator Style Measure (Norton, 1978). Results show statistically significant relationships between different personality patterns and styles of communication and suggest that narcissistic, histrionic and compulsive patterns are related to positive communication styles in a non-clinical sample. The implications of this study are discussed. PMID- 24230949 TI - Psychometric properties of the Social Physique Anxiety Scale (SPAS-7) in Spanish adolescents. AB - The purpose of this study was to validate the Spanish version of Motl and Conroy's model of the Social Physique Anxiety Scale (SPAS-7). To achieve this goal, a sample of 398 secondary school students was used, and the psychometric properties of the SPAS-7 were examined through different analyses. The results supported the seven-item model, although the item 5 did not show any significant correlation with two items from this model and had a lower factor loading than the rest of items. The structure of the model was invariant across gender and Body Mass Index (BMI). Alpha value over .70 and suitable levels of temporal stability were obtained. Girls and students classified according to the BMI as overweight and obese had higher scores in social physique anxiety than boys and the group classified as underweight and normal range. The findings of this study provided reliability and validity for the SPAS-7 in a Spanish adolescent sample. PMID- 24230950 TI - Academic performance and social competence of adolescents: predictions based on effortful control and empathy. AB - This study explored the predictive power of effortful control (EC) on empathy, academic performance, and social competence in adolescents. We obtained self report measures of EC and dispositional empathy in 359 students (197 girls and 162 boys) aged between 12 and 14 years. Each student provided information about the prosocial behavior of the rest of his/her classmates and completed a sociogram. At the end of the school year, we calculated the mean grade of each student and the teacher responsible for each class completed a questionnaire on the academic skills of his/her students. The study confirmed the existence of a structural equation model (SEM) in which EC directly predicted academic performance and social competence. Additionally, empathic concern partially mediated the effect of EC on social competence. Finally, social competence significantly predicted academic performance. The article discusses the practical applications of the model proposed. PMID- 24230951 TI - Think manager--think male in adolescents and its relation to sexism and emotions in leadership. AB - From the perspective of the Think manager--think male, this study was conducted to examine the type of leadership role depending on gender in a sample of 158 Spanish adolescents -according to three types of leaders: "male middle leader", "female middle leader" and "middle leader in general". The kind of emotional expression (positive and negative) evoked by their leadership behaviors (task- and relationship- oriented) was also analyzed. Lastly, whether adolescents' sexist beliefs affected the attribution of traits and the emotional expression towards these leaders was examined. Results showed that task-oriented traits were more characteristic of the leadership role than relationship-oriented traits. Adolescents expressed more positive emotions towards a task-oriented leader and towards a leader behaving in ways associated with both task- and relationship- oriented styles, but only for men. Finally, hostile sexism predicted fewer task oriented traits to female leaders, more negative affect towards task-oriented male leaders and towards counter-stereotypic leaders. These results were moderated by the sex of adolescents. PMID- 24230952 TI - High trait anger Mexican youth: characteristics, parental anger, and counseling needs. AB - This study compared three groups of Mexican youth: (1) high trait anger adolescents recognizing anger problems (HR); (2) high trait anger youth not reporting anger problems (HNR); and (3) low trait anger adolescents not reporting anger problems (LNR). The HR group was sizable, representing 21% of all students and 72% of high anger youth. Compared to LNR, high anger groups (HR and HNR) experienced more angry feelings, engaged in anger suppression (e.g., holding anger in and harboring grudges) and aggressive anger expression (e.g., urges to aggression, physical aggressive anger expression toward others and toward self and objects), and reported lower internal and external anger control (e.g., relaxing and controlling one's behavior when angry). High anger groups also reported greater trait anger in both parents than LNR, suggesting parent's anger is a risk factor for anger in adolescents. HR and HNR groups, however, did not differ on any variable. Findings for high anger groups supported the intensity, aggression, and reduced positive coping hypotheses of State-Trait Anger Theory. Findings were also discussed in terms of the counseling needs of high anger Mexican youth and State-Trait Theory. PMID- 24230953 TI - Sense of coherence and biopsychosocial health in Spanish adolescents. AB - The aim of this study was to analyse the effect of the SOC on the main components of biopsychosocial health separately, thereby contributing to a better understanding of the relationship between the SOC and health in adolescence. The sample consisted of 7,580 Spanish adolescents aged 13 to 18 who had participated in the 2009/10 edition of the WHO international survey Health Behaviour in School aged Children. Using multivariate analysis of variance, the effects of the SOC and demographic variables (including interaction effects between them) on different health components were analysed. A higher SOC was associated with better self-rated health, lower frequency of somatic and psychological complaints and higher quality of life and life satisfaction. Thus, results support the association between SOC and positive health outcomes, especially for the psychological components of health. In addition, the effect of SOC on the various health components was homogeneous among all of the adolescents, regardless of gender and age. PMID- 24230954 TI - Relapse situations according to Marlatt's taxonomy in smokers. AB - Relapse is common during the process of giving up smoking. The aim of the present study is to explore the relapse situations, according to Marlatt's relapse taxonomy, in a sample of 428 smokers (43.9% men and 56.1% women) who participated in a cognitive-behavior psychological treatment for quitting smoking. At the end of the treatment, 221 participants were abstinent, of whom 119 (41.2% men and 58.8% women) relapsed in the course of the 12-month follow-up, the majority in the first 3 months (69.74%). Most of the relapses were attributed to intrapersonal and environmental determinants (61.33%), the most common of which were "coping with negative emotional states" (38.65%), followed by "giving in to temptations or urges" (9.24%) and "testing personal control" (8.40%). Interpersonal determinants occurred in 38.66% of relapses, this percentage being made up mostly of "social pressure", which was the relapse situation in 34.46% of all relapses. These results, similar to those of Marlatt's original studies and others, contribute to improving our knowledge of the relapse situations process, with a view to interventions that may help to avoid it. PMID- 24230955 TI - A meta-analysis of the diagnostic accuracy of the SCOFF. AB - A meta-analysis was conducted to reach a pooled estimate of the diagnostic accuracy of the SCOFF. The 15 selected studies represented a total of 882 cases and 4350 controls. The main criterion for inclusion was that the primary study had provided diagnostic classification with both a diagnostic reference and with the SCOFF (with five items and a cut-off point of two). The pooled estimates were .80 (sensitivity) and .93 (specificity). The moderator variables gender and type of measure for the diagnostic reference (interview versus psychometric tests) account for part of the observed variability. For diagnostic references based on interviews the estimate of the efficacy improves significantly. For the studies that match this criterion the sensitivity is .882 and the specificity .925 (diagnostic odds ratio, 92.19). The main conclusion was that the five questions of the SCOFF constitute a very useful screening tool, in several languages; it is highly recommended for screening purposes. PMID- 24230956 TI - Confirmatory factor analysis of the generalized self-efficacy scale in Brazil and Portugal. AB - This study aims to evaluate the construct validity, internal consistency and cross-cultural invariance of the Generalized Self-Efficacy Scale-Portuguese version (GSE) in a Brazilian and Portuguese sample. The GSE is composed of 10 items, designed to parsimoniously and comprehensively assess self-efficacy beliefs to deal with a wide range of stress-inducing situations. The construct validity (factorial, convergent and discriminant) and internal consistency of the instrument were established within a sample of 304 Portuguese adolescents (study 1) and a sample of 477 Brazilian adolescents (study 2). Then, the invariance of the GSE was tested in a sample of Brazilian adolescents (study 3), using Multigroup Confirmatory Factor Analysis (MGCFA). In the first two studies, the construct validity of the GSE was demonstrated in its three components and the reliability of the scales was confirmed based on satisfactory levels of internal consistency. In the third study, the cross-cultural invariance of the instrument was established. This work adds to previous research on generalized self-efficacy instruments, with good psychometric qualities. Moreover, comparisons can now be made with confidence using this instrument among adolescent samples from Portugal and Brazil. PMID- 24230957 TI - Psychometric evaluation of the Sociocultural Attitudes Towards Appearance Questionnaire-3 among Brazilian young adults. AB - The objective was evaluating the psychometric properties of the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3) among Brazilian young adults of both genders. The sample was composed by 506 undergraduate students (295 females and 211 males), aged between 17 and 29 years old. Exploratory and confirmatory factor analyses were used for construct validity (N = 506). Correlations between the SATAQ-3 scores and those of the Tripartite Influence Scale (TIS) and Body Shape Questionnaire (BSQ) were used for convergent validity. Reliability was assessed through internal consistency (alpha) and reproducibility (test-retest) through comparison of the means obtained at two different time points and through intra-class correlation. The scale presented a factor structure composed of five factors, replicated in the confirmatory factor analysis with satisfactory values for the measurements of adjustment to the model. Correlations with the BSQ and TIS scores were rho = .52 and rho = -.35, respectively. Cronbach's alpha coefficients were satisfactory, and their stability was demonstrated. Brazilian SATAQ-3 had good validity and reproducibility, being indicated for use in samples of Brazilian youths. PMID- 24230958 TI - Spanish version of the Meta-Cognitions Questionnaire 30 (MCQ-30). AB - The Meta-cognitions Questionnaire 30 (MCQ-30; Wells & Cartwright-Hatton, 2004) has been used to assess individual differences in metacognitive beliefs considered to be central in the metacognitive theory of generalized anxiety disorder (Wells, 2005). In the present study, the psychometric properties, reliability, and validity of a Spanish adaptation of the MCQ-30 were tested in a broad sample of participants (N = 768) of Spanish nationality aged 16-81 years (31.1% males, 68.9% females). Confirmatory factor analysis showed the expected five-factor structure, which was found to be invariant across gender. Internal consistency and test-retest reliability of the subscales were adequate, and the expected relationships to theoretically related variables such as pathological worry, meta-worry, thought suppression and trait anxiety were obtained. Convergent validity with other measures of beliefs about worry was also found. Taken together, these findings suggest that the Spanish version of the MCQ-30 is a valid instrument for evaluating metacognitive beliefs in the Spanish-speaking population. PMID- 24230959 TI - When interdependence shapes social perception: cooperation and competition moderate implicit gender stereotyping. AB - We examined the influence of interdependence goals on the accessibility of implicit gender stereotypical associations. Participants were asked to cooperate with or compete against a woman on a mathematical abilities task and subsequently the relative activation of positive and negative warmth and competence traits was measured using a primed categorization task. Results showed that female primes (vs. male primes) facilitated the activation of low warmth and high competence in the competition condition, whereas high warmth was activated in the cooperation condition and no differences were found for competence traits. These results are discussed referring to the stereotype content model and the compensation effect in person perception. The goal dependent nature of implicit gender stereotypes is emphasized. PMID- 24230960 TI - Human embryonic stem cell science and policy: the case of Iran. AB - The paper is based on a large qualitative study of ethics, policy and regulation of human embryonic stem cell (hESC) science in Iran. This case study in five academic research centres used semi-structured interviews to examine in depth the views of stem cell scientists, embryologists and ethics committee members on hESC research policy in this Shia Muslim country. Although Iran's policy approach has been considered 'intermediate', what is described here seems to be a 'more flexible' policy on hESC science. This article describes three arguments to explain why Iran has shaped such a policy. These are: (1) a flexibility of the Shia tradition has allowed for hESC science; (2) permissive policy related to other fields of biomedicine, such as new assisted reproductive technologies, facilitated approval of hESC research; and (3) a lack of public debate of bioscience in Iran influences how its hESC research policy is perceived. Based on the empirical data, this paper then expands and refines the conceptual bioethical basis for the co-production of science, policy, and society in Iran. The notion of co-production implies that scientists, policy-makers, and sometimes other societal actors cooperate in the exchange, production, and application of knowledge to make science policy. PMID- 24230961 TI - The influence of school holiday timing on epidemic impact. AB - The impact of reactive school closure on an epidemic is uncertain, since it is not clear how an unplanned closure will affect social mixing patterns. The effect of school holidays on social mixing patterns is better understood. Here, we use mathematical models to explore the influence of the timing of school holidays on the final size and peak incidence of an influenza-like epidemic. A well-timed holiday can reduce the impact of an epidemic, in particular substantially reducing an epidemic's peak. Final size and peak incidence cannot both be minimized: a later holiday is optimal for minimizing the final size, while an earlier holiday minimizes peak incidence. Using social mixing data from the UK, we estimated that, had the 2009 influenza epidemic not been interrupted by the school summer holidays, the final size would have been about 20% larger and the peak about 170% higher. PMID- 24230962 TI - A systematic review and meta-analysis of total thyroidectomy versus bilateral subtotal thyroidectomy for Graves' disease. AB - BACKGROUND: Our aim was to perform a meta-analysis of high-quality published trials, randomized and observational, comparing total thyroidectomy (TT) and bilateral subtotal thyroidectomy (ST) for Graves' disease. METHODS: All studies published from 1970 to August 2012 were identified. All randomized controlled trials (RCTs) were included. Selection of high-quality, nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies). Recurrent hyperthyroidism during follow-up, progression of ophthalmopathy, postoperative temporary and permanent hypoparathyroidism, and permanent recurrent laryngeal nerve (RLN) palsy were compared using odds ratios (ORs). RESULTS: Twenty-three studies were included (4 RCTs and 19 NRCTs) compromising 3,242 patients (1,665 TT, 1,577 ST). TT was associated with a decrease in recurrent hyperthyroidism (P < .00001; OR, 0.10; 95% confidence interval [CI], 0.06-0.18), but with an increase in both temporary (P < .00001; OR, 2.70; 95% CI, 2.04-3.56) and permanent hypoparathyroidism (P = .005; OR, 2.91; 95% CI, 1.59-5.32). Progression of ophthalmopathy (P = .76; OR, 0.90; 95% CI, 0.48-1.71) and permanent RLN palsy (P = .82; OR, 0.91; 95% CI, 0.41-2.02) were similar. CONCLUSION: TT offers a better chance of cure of hyperthyroidism than bilateral ST and can be accomplished safely with only a small increase in temporary and permanent hypoparathyroidism. PMID- 24230963 TI - Prevalence of dysmenorrhea in university students in Turkey: effect on daily activities and evaluation of different pain management methods. AB - This study was conducted to determine the following among a group of female university students: the prevalence of dysmenorrhea; pain severity ratings; methods used to manage dysmenorrhea; and the effect of dysmenorrhea on daily activities, school attendance, and ability to communicate with friends. This cross-sectional study was conducted between December 2009 and February 2010 at a public university located in Istanbul, in the northwest area of Turkey. The study group included 1515 female students. Data were collected from the female students in the study group using a self-report questionnaire; the severity of dysmenorrhea was determined with the visual analog scale. The data were examined with mean, percentages, chi-square analysis, and logistic regression. The prevalence of dysmenorrhea in the study group was 85.7%. Of this group of subjects with dysmenorrhea, 30.4% described their menstrual pain as severe, 49.8% as moderate, and 19.8% as mild. The mean severity of pain among the students was 6.33 +/- 2.32 on the VAS. The majority of participants who experienced moderate or severe pain regularly used analgesics for pain management, and participants who experienced severe pain used analgesics before the beginning of menstruation. Participants who experienced moderate pain used herbal tea, massage, heat application, rest, and distraction for pain management. Participants who experienced severe pain consulted a physician and that a significant difference existed between the dysmenorrhea rating groups in this regard (p < .001). Severe pain was significantly associated with school absenteeism and limitations in social activities/functioning (p < .001). Dysmenorrhea is highly prevalent among university students and is related to school absenteeism, ability to participate in and enjoy daily activities, and limitations in social activities/functioning. PMID- 24230964 TI - The impact of neuropsychiatric symptoms on caregiver distress and quality of life in persons with dementia in an Asian tertiary hospital memory clinic. AB - BACKGROUND: This study aims to determine the prevalence, profile, and severity of neuropsychiatric symptoms (NPS) across the dementia continuum and their relative impact on caregiver distress and quality of life (QoL) in persons with dementia (PWD). METHOD: Six hundred and sixty-seven PWD and their family caregivers presented to a memory clinic in a tertiary hospital across a 60-month period. Clinicians determined the dementia diagnosis and severity using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition and the Clinical Dementia Rating scale, respectively. The Neuropsychiatric Inventory Questionnaire was administered to assess NPS in PWD and the corresponding distress experienced by the caregiver. QoL for PWD (PWD-QoL) was assessed by the Quality of Life Alzheimer's Disease scale. RESULTS: Ninety-six percent of PWD presented with at least one NPS, 18% experiencing mild, 31% moderate, and 47% severe symptoms, respectively. While agitation (63.1%), apathy (61.8%), depression (55.5%), and irritability (55.5%) were the most common NPS; disinhibition (35.2%), hallucination (25.5%), and elation (14.2%) were the least common. NPS increased generally but differentially as dementia progressed and significantly predicted caregiver distress (etap 2 = 0.732, p < 0.0001) and PWD-QoL (etap 2 = 0.066, p < 0.0001). Factor analysis revealed two NPS clusters, disruptive and affective; the former exerting greater impact on caregiver distress and the latter on PWD-QoL. CONCLUSION: The results show a high prevalence of NPS which increase caregiver distress and negatively impact PWD-QoL. The differential profile of NPS across the dementia stages warrants stage-specific interventions and due consideration in resource planning and service design for PWD and their caregivers. PMID- 24230965 TI - The impact of cataract surgery on depressive symptoms for bilateral cataract patients in Ho Chi Minh City, Vietnam. AB - BACKGROUND: Depression is common among older populations with cataract. However, the impact of cataract surgery on depression in both developed and developing countries remains unclear. The aim of this study is to determine the impact of cataract surgery on depressive symptoms and to examine the association between objective visual measures and change in depressive symptoms after surgery among a Vietnamese population in Ho Chi Minh City. METHODS: A cohort of older patients with bilateral cataract were assessed the week before and one to three months after first eye surgery only or first- and second-eye cataract surgeries. Visual measures including visual acuity, contrast sensitivity, and stereopsis were obtained. Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression Scale (CES-D). Descriptive analyses and a generalized estimating equations (GEE) analysis were undertaken to determine the impact of cataract surgery on depressive symptoms. RESULTS: Four hundred and thirteen participants were recruited into the study before cataract surgery. Two hundred and forty-seven completed the follow-up assessment after surgery. There was a significant decrease (improvement) of one point in the depressive symptoms score (p = 0.04) after cataract surgery, after accounting for potential confounding factors. In addition, females reported a significantly greater decrease (improvement) of two points in depressive symptom scores (p = 0.01), compared to males. However, contrast sensitivity, visual acuity, and stereopsis were not significantly associated with change in depressive symptoms scores. First-eye cataract surgery or both-eye cataract surgery did not modify the change in depressive symptoms score. CONCLUSION: There was a small but significant improvement in depressive symptoms score after cataract surgery for an older population in Vietnam. PMID- 24230966 TI - Coincident electron channeling and cathodoluminescence studies of threading dislocations in GaN. AB - We combine two scanning electron microscopy techniques to investigate the influence of dislocations on the light emission from nitride semiconductors. Combining electron channeling contrast imaging and cathodoluminescence imaging enables both the structural and luminescence properties of a sample to be investigated without structural damage to the sample. The electron channeling contrast image is very sensitive to distortions of the crystal lattice, resulting in individual threading dislocations appearing as spots with black-white contrast. Dislocations giving rise to nonradiative recombination are observed as black spots in the cathodoluminescence image. Comparison of the images from exactly the same micron-scale region of a sample demonstrates a one-to-one correlation between the presence of single threading dislocations and resolved dark spots in the cathodoluminescence image. In addition, we have also obtained an atomic force microscopy image from the same region of the sample, which confirms that both pure edge dislocations and those with a screw component (i.e., screw and mixed dislocations) act as nonradiative recombination centers for the Si-doped c-plane GaN thin film investigated. PMID- 24230967 TI - The influence of air content in water on ultrasonic cavitation field. AB - Cavitation is a complex physical phenomenon affected by many factors, one of which is the gas dissolved in the medium. Researchers have given some efforts to the influence of gas content on sonoluminescence or some specific chemical reactions in and around the bubble, but limited work has been reported about the influence on the ultrasonic cavitation field distribution. In this work, the intensity distribution of the ultrasound field in a cleaning tank has been measured with the hydrophone. After analysed and visualised by MATLAB software, it was found that the cavitation intensity distribution in degassed water was much better than that in tap water. And further study proved that degassing process can improve the cavitation effect dramatically both in intensity and scope. Finally, the cavitation fields in mediums with different gas content were measured and the specific influence of air content on cavitation field was discussed. PMID- 24230968 TI - The relationship between coping, health competence and patient participation among patients with inactive inflammatory bowel disease. AB - BACKGROUND: Coping is an integral part of adjustment for patients with Inflammatory Bowel Disease but has not been well described in the literature. This study explored the relationship between coping, perceived health competence, patient preference for involvement in their treatment, depression and quality of life, particularly among patients with inactive disease (in remission). METHODS: Subjects (n=70) with active and inactive IBD completed questionnaires, including the Inflammatory Bowel Disease Quality of Life Questionnaire, Beck Depression Inventory, Perceived Health Competence Scale and the Coping Inventory for Stressful Situations. The Harvey Bradshaw Index measured disease activity. RESULTS: Patients with inactive IBD demonstrated significantly more interest in participating in their treatment (p<.05), more perceived health competence (p=.001), less depressive symptoms (p<.001), more task oriented coping (p=.02), and better quality of life than those with active disease. Only Task Oriented Coping was significantly negatively associated with the number of flares among inactive patients (p<.001). Patient preference for participation in treatment was inversely associated with Avoidance (p=.005), Distraction (p=.008), and Social Diversion (p=.008) coping among inactive patients. CONCLUSION: Among patients in remission, those who expressed a greater interest in treatment participation were also less likely to practice maladaptive coping. Our data demonstrate that a more active coping style may be associated with improved health outcome. Compared to patients with active disease, patients in remission are more likely to employ task oriented coping, demonstrate a higher interest in treatment participation, report greater perceived control of their health, and exhibit less depression symptoms. Our findings may increase awareness of the importance of identifying coping strategies for IBD patients, including those in remission. PMID- 24230969 TI - Differences in the management of pediatric and adult onset ulcerative colitis- lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis. AB - An expert panel of the European Crohn's and Colitis Organisation (ECCO) and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) initiated a consensus process to produce the first pediatric specific ulcerative colitis (UC) guidelines based on a systematic literature review. Treatment strategies must reflect that pediatric-onset UC has a slightly different phenotype than adult-onset disease with more often extensive (pancolitis) and more aggressive disease course. Other pediatric-specific aspects include growth, puberty, bone density accrual and emotional development and body image acquisition. These differences and others influenced the development of pediatric treatment algorithms. It is recommended that virtually all children with UC must be treated with some maintenance therapy and 5-ASA requirement and dosing are often higher in children. A larger number of children are at risk for steroid-dependency, and this should not be tolerated; steroid sparing strategies with early use of immunosuppressors are recommended in high-risk patients. On the other hand, the safety profile of immunosuppressive therapy in children includes the rare forms of lymphomas and many future treatment years. Colectomy and pouch formation should be balanced in the treatment algorithms against the higher rate of future infertility in girls. The acute and on-going management of pediatric UC should be guided by evidence- and consensus-based balanced decisions, reflecting a vision of long-term treatment goals. PMID- 24230970 TI - Coping is excellent in Swiss Children with inflammatory bowel disease: results from the Swiss IBD cohort study. AB - BACKGROUND: Inflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment. METHODS: Data were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by PCDAI and PUCAI. The age adapted KIDSCREEN questionnaire was evaluated for 110 children with IBD (64 with Crohn's disease 46 with ulcerative colitis). Data were analyzed with respect to established reference values of healthy controls. RESULTS: In the KIDSCREEN index a moderate impairment was only found for physical wellbeing due to disease activity. In contrast, mental well being and social support were even better as compared to control values. A subgroup analysis revealed that this observation was restricted to the children in the German speaking part of Switzerland, whereas there was no difference compared to controls in the French part of Switzerland. Furthermore, autonomy and school variables were significantly higher in the IBD patients as compared to controls. CONCLUSIONS: The social support for children with IBD is excellent in this cohort. Only physical well-being was impaired due to disease activity, whereas all other KIDSCREEN parameters were better as compared to controls. This indicates that effective coping and support strategies may be able to compensate the burden of disease in pediatric IBD patients. PMID- 24230971 TI - Particle self-assembly at ionic liquid-based interfaces. AB - This review presents an overview of the nature of ionic liquid (IL)-based interfaces and self-assembled particle morphologies of IL-in-water, oil- and water-in-IL, and novel IL-in-IL Pickering emulsions with emphasis on their unique phenomena, by means of experimental and computational studies. In IL-in-water Pickering emulsions, particles formed monolayers at ionic liquid-water interfaces and were close-packed on fully covered emulsion droplets or aggregated on partially covered droplets. Interestingly, other than equilibrating at the ionic liquid-water interfaces, microparticles with certain surface chemistries were extracted into the ionic liquid phase with a high efficiency. These experimental findings were supported by potential of mean force calculations, which showed large energy drops as hydrophobic particles crossed the interface into the IL phase. In the oil- and water-in-IL Pickering emulsions, microparticles with acidic surface chemistries formed monolayer bridges between the internal phase droplets rather than residing at the oil/water-ionic liquid interfaces, a significant deviation from traditional Pickering emulsion morphology. Molecular dynamics simulations revealed aspects of the mechanism behind this bridging phenomenon, including the role of the droplet phase, surface chemistry, and inter particle film. Novel IL-in-IL Pickering emulsions exhibited an array of self assembled morphologies including the previously observed particle absorption and bridging phenomena. The appearance of these morphologies depended on the particle surface chemistry as well as the ILs used. The incorporation of particle self assembly with ionic liquid science allows for new applications at the intersection of these two fields, and have the potential to be numerous due to the tunability of the ionic liquids and particles incorporated, as well as the particle morphology by combining certain groups of particle surface chemistry, IL type (protic or aprotic), and whether oil or water is incorporated. PMID- 24230972 TI - Genome-wide identification and analysis of FK506-binding protein family gene family in strawberry (Fragaria * ananassa). AB - The FK506 binding proteins (FKBPs) are abundant and ubiquitous proteins belonging to the large peptidyl-prolylcis-trans isomerase superfamily. FKBPs are known to be involved in many biological processes including hormone signaling, plant growth, and stress responses through a chaperone or an isomerization of proline residues during protein folding. The availability of complete strawberry genome sequences allowed the identification of 23 FKBP genes by HMMER and blast analysis. Chromosome scaffold locations of these FKBP genes in the strawberry genome were determined and the protein domain and motif organization of FaFKBPs analyzed. The phylogenetic relationships between strawberry FKBPs were also assessed. The expression profiles of FaFKBPs genes results revealed that most FaFKBPs were expressed in all tissues, while a few FaFKBPs were specifically expressed in some of the tissues. These data not only contribute to some better understanding of the complex regulation of the strawberry FKBP gene family, but also provide valuable information for further research in strawberry functional genomics. PMID- 24230973 TI - Analyzing methods for path mining with applications in metabolomics. AB - Metabolomics is one of the key approaches of systems biology that consists of studying biochemical networks having a set of metabolites, enzymes, reactions and their interactions. As biological networks are very complex in nature, proper techniques and models need to be chosen for their better understanding and interpretation. One of the useful strategies in this regard is using path mining strategies and graph-theoretical approaches that help in building hypothetical models and perform quantitative analysis. Furthermore, they also contribute to analyzing topological parameters in metabolome networks. Path mining techniques can be based on grammars, keys, patterns and indexing. Moreover, they can also be used for modeling metabolome networks, finding structural similarities between metabolites, in-silico metabolic engineering, shortest path estimation and for various graph-based analysis. In this manuscript, we have highlighted some core and applied areas of path-mining for modeling and analysis of metabolic networks. PMID- 24230974 TI - [Major chest wall resection for the treatment of invasive breast carcinoma: A series of 33 patients]. AB - INTRODUCTION: Breast cancer can spread to the chest wall. It is an aggressive stage of poor prognosis. We have developed a technique of major chest wall resection extended beyond the breast area in order to reduce the recurrence. PATIENTS AND METHODS: This is a retrospective single-center series of 33 patients with breast cancer spread to the chest wall without metastasis (13 patients present with primary breast cancer and 20 patients present with recurrent breast cancer) treated by major chest wall resection between January 1993 and January 2013, by the same surgeon. Analysis of the results was made by another surgeon. RESULTS: Patients aged between 27-83years with an average of 55years. The removed parts measured 350cm(2) to 1200cm(2), and the average duration of complete healing was 7.9months. The mean follow-up time was 122months (6months-240months). The 1 year survival was 84.4%, at 2years 72.6%, at 3years 69.5% and at 5 years of 66.4%. CONCLUSION: The technique of major chest wall resection is simple and reproducible. Breast cancer with chest wall extension has a poor prognosis. At the end of the study, 20 of 33 patients who benefit from this technique are still alive. PMID- 24230975 TI - Long-term exposure investigating the estrogenic potency of estriol in Japanese medaka (Oryzias latipes). AB - The growth, development, and ERalpha and Vtg-I gene expressions of Japanese ricefish (Oryzias latipes; medaka) exposed to different concentrations of estriol (E3), including one environmentally relevant concentration, during embryo-adult life stages were evaluated. At the early life stage, fertilized eggs were exposed to 5, 50, 500, 5000ng/L E3 for 15days, and the hatched fry were exposed continuously to the same concentrations for an additional 15days. Exposure to 500 and 5000ng/L E3 resulted in adverse effects on hatchability and time to hatching. At 5000ng/L, the gross abnormality rate was increased and the number of females that hatched was twice that of males. When the fish were exposed to 5-5000ng/L E3 for further 60days, the male hepatosomatic index (HSI) was increased at 5000ng/L. The female gonadosomatic index (GSI) was decreased at 500 and 5000ng/L E3, while the male GSI at 5000ng/L E3 was increased and sex reversal was also found at this concentration. Quantitative RT-PCR showed that the hepatic vitellogenin-I (Vtg-I) genes were up-regulated in females at 500 and 5000ng/L E3 and in males at all E3 concentrations, whereas E3 did not affect estrogen receptor alpha (ERalpha) mRNA transcription. These results showed that E3 at environmental concentration of 5ng/L has no adverse effects on growth and development of the Japanese medaka. However, in this study, if we only focused on Vtg gene change in males, E3 had strong estrogenic effects on male medaka under the conditions of these experiments. PMID- 24230976 TI - Cadmium-induced changes of gypsy moth larval mass and protease activity. AB - Cadmium uptake takes place mainly through food. Lymantria dispar larvae were exposed to dietary cadmium in concentrations of 10 and 30MUg Cd/g dry food (NOEC, no-observed-effect and LOEC, lowest-observed-effect concentration, respectively) for acute and chronic treatment and recovery. We established that metal contamination decreased mass only during the chronic treatment at 30MUg Cd/dry food with no recovery on removal of cadmium for 3days. Significant reduction of protease activity was detected at LOEC after the acute and chronic treatments. Protease showed enhanced plasticity with regard to the fitness trait (mass) during environmental stress and the higher cadmium load, when it changed. The statistically significant higher index of phenotypic plasticity for protease correlated with lower variability. Protease isoforms at the same cadmium treatments differed between genotypes, while some protease isoforms from one egg mass differed between cadmium treatments. Owing to the low sensitivity and plasticity of mass change during exposure to cadmium, as well as its small influence, we concluded that larval mass is not a good indicator of cadmium presence in food. We suggest that proteases, with further research, might be a suitable indicator of dietary cadmium contamination, as well as nutriment utilization during heavy metal stress. PMID- 24230977 TI - Occurrence of weak mutators among avian pathogenic Escherichia coli (APEC) isolates causing salpingitis and peritonitis in broiler breeders. AB - A collection of 46 avian pathogenic Escherichia coli (APEC) isolates was examined for the presence of mutators by determining the rate of mutation to rifampicin resistance. The collection included 34 E. coli isolates obtained in pure culture from chronic lesions of salpingitis and peritonitis in 34 broiler breeders, of which 12 were associated with the development of secondary septicemia. Twelve additional isolates were obtained from a clonal outbreak (ST95) of E. coli peritonitis syndrome (EPS), the lesions of which changed gradually over time into a subacute/chronic form. The hypothesis of the present study was that mutation rates would be higher for chronic infection isolates than for isolates from acute infections/exacerbations. The distribution of mutation rates followed a pattern similar to that found for other clinical isolates of E. coli, with a modal/median value of 1.47 * 10(-8). Of the 46 isolates, 24% (n=11) were weakly hypermutable (2.00 * 10(-8) <= MU<2.00 * 10(-7)), however, no strong mutators were detected (MU >= 2.00 * 10(-7)). Chronic salpingitis isolates had the highest proportion (45%, P=0.001) of weak mutators and also, significantly higher mutation rates (P=0.003) compared to isolates that caused septicemia (4%). In addition, mutation rates were significantly lower among ST95 isolates (P<0.0005), and among isolates from the same clonal group as ST95 (P=0.027), when compared to isolates from other groups. Although a clear association with the time phase of infection (as lesions of EPS became more chronic) could not be observed (rho=0.523, P=0.081), a higher frequency of weak mutators among chronic infection isolates suggests that increased mutation rates play a role in adaptation of APEC to long-term persistence in an infected host environment. PMID- 24230979 TI - A meta-analysis of randomized head-to-head trials for effects of rosuvastatin versus atorvastatin on apolipoprotein profiles. AB - To determine which statin will better improve the apolipoprotein (Apo) profiles (ApoA-I levels, ApoB levels, and ApoB/A-I ratios), we performed a meta-analysis of randomized head-to-head trials of rosuvastatin versus atorvastatin therapy. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2012 using Web-based search engines (PubMed and OVID). The search terms included "apolipoprotein," "rosuvastatin," "atorvastatin," "randomized," "randomly," and "randomization." Of 42 potentially relevant studies initially screened, 25 reports of randomized trials enrolling 14,283 patients were included. A pooled analysis for the percentage of changes in ApoA-I demonstrated a benefit of rosuvastatin versus atorvastatin in the comparison of all rosuvastatin/atorvastatin dose ratios (mean difference 2.97%, 3.39%, 5.77%, and 6.25%). For the percentage of changes in ApoB, a benefit was seen for rosuvastatin versus atorvastatin in the 1/1 (-6.06%) and 1/2 dose ratio (-1.80%). However, a benefit was seen for atorvastatin versus rosuvastatin in the 1/4 (2.38%) and 1/8 dose ratio (6.59%). The pooled analysis for the percentage of changes in the Apo B/A-I ratios demonstrated a benefit for rosuvastatin versus atorvastatin in the 1/1 (-7.22%) and 1/2 dose ratio (-3.51%), with no difference in the 1/4 dose ratio. In contrast, a benefit was seen for atorvastatin versus rosuvastatin in the 1/8 dose ratio (4.03%). In conclusion, rosuvastatin might increase Apo A-I levels at all dose ratios and decrease ApoB levels and ApoB/A-I ratios in the 1/1 and 1/2 dose ratio versus atorvastatin. Only higher dose atorvastatin appeared to be more effective for the reduction in ApoB levels (1/4 and 1/8 dose ratio) and Apo B/A-I ratios (1/8 dose ratio). PMID- 24230980 TI - Prevalence and clinical correlates of right ventricular dysfunction in patients with hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HC) is a disease that mainly affects the left ventricle (LV), however recent studies have suggested that it can also be associated with right ventricular (RV) dysfunction. The objective of this study was to determine the prevalence of RV dysfunction in patients with HC and its relation with LV function and outcome. A total of 324 consecutive patients with HC who received care at Stanford Hospital from 1999 to 2012 were included in the study. A group of 99 prospectively recruited age- and gender-matched healthy volunteers were used as controls. RV function was quantified using the RV fractional area change, tricuspid annular plane systolic excursion (TAPSE), and RV myocardial performance index (RVMPI). Compared with the controls, the patients with HC had a higher RVMPI (0.51 +/- 0.18 vs 0.25 +/- 0.06, p <0.001) and lower TAPSE (20 +/- 3 vs 24 +/- 4, p <0.001). RV dysfunction based on an RVMPI >0.4 and TAPSE <16 mm was found in 71% and 11% of the HC and control groups, respectively. Worst LV function and greater pulmonary pressures were independent correlates of RV dysfunction. At an average follow-up of 3.7 +/- 2.3 years, 17 patients had died and 4 had undergone heart transplantation. LV ejection fraction <50% and TAPSE <16 mm were independent correlates of outcome (hazard ratio 3.98, 95% confidence interval 1.22 to 13.04, p = 0.02; and hazard ratio 3.66, 95% confidence interval 1.38 to 9.69, p = 0.009, respectively). In conclusion, RV dysfunction based on the RVMPI is common in patients with HC and more frequently observed in patients with LV dysfunction and pulmonary hypertension. RV dysfunction based on the TAPSE was independently associated with an increased likelihood of death or transplantation. PMID- 24230981 TI - ISO 16840-2:2007 load deflection and hysteresis measurements for a sample of wheelchair seating cushions. AB - Load deflection and hysteresis measurements were made on 37 wheelchair seating cushions according to ISO 16840-2:2007. Load deflection plots for all 37 cushions are reported and fundamental aspects of graph interpretation discussed. ISO hysteresis data are also reported and interpretation discussed. PMID- 24230982 TI - Automatic distinction of upper body motions in the main anatomical planes. AB - The assessment of spinal mobility and function is gaining clinical importance for the diagnosis and monitoring of low back pain, but its measurement and evaluation remains difficult. As a critical step towards non-supervised assessment of spinal functional, the aim of this study was to assess the efficacy of symmetrical sensors fixed to the sides of the spinal column to distinguish between different upper body movements in the main anatomical planes. 429 healthy volunteers underwent a defined choreography including repeated upper body flexion, extension, lateral bending and axial rotation exercises. The movements were assessed using the Epionics SPINE sensor system. Two pattern recognition models were developed and applied to distinguish between the different movements in a frame-by-frame manner, as well as for whole motion sequences. On average, it was possible to differentiate between different upper body movements with a sensitivity of over 96% for both modelling approaches. The largest type II error was the incorrect identification of extension, possibly due to deviations from the reference standing posture during measurements and small changes in the lordotic angle during extension. The use of two sagittal sensors attached symmetrically to the back therefore seems to allow the distinction of upper body movements in a robust manner, and therefore opens perspectives for the unsupervised recognition of movements and functional activity over extended periods. PMID- 24230983 TI - [The ankle-brachial index as a screening technique: a promese or a reality?]. PMID- 24230984 TI - The development of Web-based surveillance provides new insights into the burden of norovirus outbreaks in hospitals in England. AB - A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an Internet-based front end. A standard dataset was designed to collect information describing the key epidemiological characteristics of each outbreak. In the period 1992-2008, 1817 suspected and confirmed outbreaks of norovirus in English hospitals were reported to national surveillance. After introduction of the new system there were 3980 reports of outbreaks of suspected and confirmed norovirus received in the years 2009-2011. Data from the new reporting system demonstrates that transmission of norovirus levies a heavy burden on English hospitals. On average, reported outbreaks are associated with 13,000 patients and 3400 staff becoming ill, 8900 days of ward closure and the loss of over 15,500 bed-days annually. PMID- 24230985 TI - Observer-independent quantification of insulin granule exocytosis and pre exocytotic mobility by TIRF microscopy. AB - Total internal reflection fluorescence microscopy of fluorescently labeled secretory granules permits monitoring of exocytosis and the preceding granule behavior in one experiment. While observer-dependent evaluation may be sufficient to quantify exocytosis, most of the other information contained in the video files cannot be accessed this way. The present program performs observer independent detection of exocytosis and tracking of the entire submembrane population of insulin granules. A precondition is the exact localization of the peak of the granule fluorescence. Tracking is based on the peak base radius, peak intensity, and the precrossing itineraries. Robustness of the tracking was shown by simulated tracks of original granule patterns. Mobility in the X-Y dimension is described by the caging diameter which in contrast to the widely used mean square displacement has an inherent time resolution. Observer-independent detection of exocytosis in MIN6 cells labeled with insulin-EGFP is based on the maximal decrease in fluorescence intensity and position of the centroid of the dissipating cloud of released material. Combining the quantification of KCl induced insulin exocytosis with the analysis of prefusion mobility showed that during the last 3 s pre-exocytotic granules had a smaller caging diameter than control granules and that it increased significantly immediately before fusion. PMID- 24230986 TI - Effects of overweight and obese body mass on motor planning and motor skills during obstacle crossing in children. AB - Little is known about how obesity relates to motor planning and skills during functional tasks. We collected 3-D kinematics and kinetics as normal weight (n=10) and overweight/obese (n=12) children walked on flat ground and as they crossed low, medium, and high obstacles. We investigated if motor planning and motor skill impairments were evident during obstacle crossing. Baseline conditions showed no group differences (all ps>.05). Increased toe clearance was found on low obstacles (p=.01) for the overweight/obese group and on high obstacles (p=.01) for the normal weight group. With the crossing leg, the overweight/obese group had larger hip abduction angles (p=.01) and medial ground reaction forces (p=.006) on high obstacles and high anterior ground reaction forces on low obstacles (p=.001). With the trailing leg, overweight/obese children had higher vertical ground reaction forces on high obstacles (p=.005) and higher knee angles (p=.01) and anterior acceleration in the center of mass (p=.01) on low obstacles. These findings suggest that differences in motor planning and skills in overweight/obese children may be more apparent during functional activities. PMID- 24230987 TI - How do we measure psychiatric diagnoses? Implications of the choice of instruments in epilepsy. AB - We evaluated several commonly used screening instruments for the detection of mood disorders, anxiety disorders, and attention-deficit hyperactivity disorder (ADHD). These were compared to a criterion-based standardized questionnaire, the Diagnostic Interview Survey (DIS)-IV, designed to make DSM-IV-TR diagnoses in the community-based study of childhood-onset epilepsy. The DIS-IV was administered to young adult cases with epilepsy at a 15-year follow-up assessment and compared to symptom screens administered at the same visit, and at a previous 9-year assessment. Among cases, the specificity of the DIS-IV ranged from 0.77 to 0.99 and the predictive value of a negative psychiatric diagnosis was similarly high. Sensitivity was lower, ranging from 0 to 0.77, with correspondingly low predictive value of a positive diagnosis. Symptom-based instruments assess current symptom burden and are useful for determining associations with ongoing seizures or quality of life. Criterion-based standardized interviews, such as the DIS-IV, provide psychiatric diagnoses over the lifetime, which is most useful in studies of epilepsy genetics and studies of comorbidities and prognosis of epilepsy. PMID- 24230988 TI - Effect of lithium-pilocarpine-induced status epilepticus on ultrasonic vocalizations in the infant rat pup. AB - Evidence shows that febrile convulsions induced in rat pups increase ultrasonic vocalizations (USVs); however, the effect of status epilepticus (SE) induced in developing rats on USVs has not been fully investigated. The goal of this study was to analyze USVs following lithium-pilocarpine-induced SE in fourteen-day-old (P14) rat pups. The rat pups were given 3-mEq/kg lithium chloride i.p. on the day before the induction of SE, which was carried out at P14 by subcutaneous injection of 100-mg/kg pilocarpine hydrochloride; control animals were given an equal volume of lithium chloride and saline on P13 and P14, respectively. Ultrasonic vocalizations were monitored at P15, P16, and P21 with a Mini 3 Bat Detector Ultra Sound Advice (15kHz-160kHz) set at 40+/-4kHz and digitally recorded in WAV format using the Audacity 1.3 beta software. A clear box (60*40*30cm) split down the middle with a holed wall was used; each pup was placed alone in one compartment, whereas its dam was placed on the other cage side at room temperature. Vocalizations were recorded over a 5-minute period, converted to sonograms and spectrograms, and analyzed using the Raven software. Parameters evaluated were as follows: USV frequency, latency to the first USV, and mean USV duration. There was a significant decrease in the latency (35.5+/ 6.9s) and duration (50.8+/-8.6s) of USVs after SE compared with the control group (81.9+/-10.8s and 78.1+/-9.9s, respectively). Status epilepticus affected male and female rats differentially. PMID- 24230989 TI - The optimal acupoint for acupuncture stimulation as a complementary therapy in pediatric epilepsy. PMID- 24230990 TI - Transient epileptic amnesia: a concise review. AB - Transient epileptic amnesia (TEA) is a distinctive syndrome and comprises episodic transient amnesia with an epileptic basis, without impairment of other aspects of cognitive function. Additional interictal memory deficits are common in TEA. An epileptic origin, after other etiologies have been excluded, should be considered and carefully investigated in patients complaining of isolated memory disturbances, particularly with recurrent short-lasting amnesic attacks. In all suspected cases of epilepsy, a detailed clinical history is of paramount importance, but ancillary tests including EEG and MRI could be very helpful. Transient epileptic amnesia is typically a benign and treatable condition. Future studies should investigate the exact mechanism(s) of this unique syndrome. PMID- 24230991 TI - L-DOPA-treatment in primates disrupts the expression of A(2A) adenosine-CB(1) cannabinoid-D(2) dopamine receptor heteromers in the caudate nucleus. AB - The molecular basis of priming for L-DOPA-induced dyskinesias in Parkinson's disease (PD), which depends on the indirect pathway of motor control, is not known. In rodents, the indirect pathway contains striatopallidal GABAergic neurons that express heterotrimers composed of A(2A) adenosine, CB(1) cannabinoid and D(2) dopamine receptors that regulate dopaminergic neurotransmission. The present study was designed to investigate the expression of these heteromers in the striatum of a primate model of Parkinson's disease and to determine whether their expression and pharmacological properties are altered upon L-DOPA treatment. By using the recently developed in situ proximity ligation assay and by identification of a biochemical fingerprint, we discovered a regional distribution of A(2A)/CB(1) /D(2) receptor heteromers that predicts differential D(2)-mediated neurotransmission in the caudate-putamen of Macaca fascicularis. Whereas heteromers were abundant in the caudate nucleus of both naive and MPTP treated monkeys, L-DOPA treatment blunted the biochemical fingerprint and led to weak heteromer expression. These findings constitute the first evidence of altered receptor heteromer expression in pathological conditions and suggest that drugs targeting A(2A)-CB(1) -D(2) receptor heteromers may be successful to either normalize basal ganglia output or prevent L-DOPA-induced side effects. PMID- 24230992 TI - Reward sensitivity and anger in euthymic bipolar disorder. AB - According to the hypersensitive behavioral approach system (BAS) model of bipolar disorder (BP), hypersensitivity of the BAS is a trait that should be present even in the euthymic state. This would be expected to result in increased anger and reward sensitivity, both of which are related to the approach system. This study examined these predictions through the use of tasks that assess different aspects of the BAS: reward sensitivity, anger and impulsivity. These characteristics were assessed using the probabilistic classification task (PCT), ultimatum game (UG) and single key impulsivity paradigm (SKIP), respectively. Participants were euthymic adult bipolar disorder patients (BP; N=40) and healthy controls (HC; N=41). In the UG, all participants showed the standard pattern of rejecting overtly unfair offers and accepting clearly fair offers; however, BPs rejected more of the moderately unfair offers than did HCs. BP and HC participants did not differ on their ability to learn, but did show different patterns of learning from reward and punishment. Learning for reward and punishment were negatively correlated in the BP group, suggesting that individuals could learn well either from reward or punishment, but not both. No correlation was found between these forms of learning in the HC group. BP patients show signs of their disorder even in the euthymic state, as seen by the dysbalance between reward and punishment learning and their residual anger in the UG. PMID- 24230993 TI - Predictors of response to second generation antipsychotics in drug naive patients with schizophrenia: a 1 year follow-up study in Shanghai. AB - Response and remission are of great importance to patients with first-episode schizophrenia. Although previous researches have revealed characteristics related to medication response, there is rarely data over remission-related factors. We presume that factors correlated to response may also influence remission in 1 year treatment for first-episode schizophrenia. 398 drug-naive patients met the criteria of schizophrenia using ICD-10 criteria were recruited from Shanghai Mental Health Center and treated with one of three second generation antipsychotics (risperidone, olanzapine or quetiapine). Patients were followed up for 1 year and assessed at 2 weeks, and then 2, 3, 6, 8 and 12 months. Severity of symptom was evaluated using the Chinese version of the Positive and Negative Syndrome Scale (PANSS). Response was defined as a reduction of 50% or more PANSS scores. The 8-item criteria of remission (proposed by the Remission of Schizophrenia Working Group) were used. Logistic regression analysis revealed that shorter duration of untreated psychosis (DUP), longer treatment time, higher baseline PANSS positive score and higher PANSS general pathological scores predicted response, and acute prodromal phase was the independent factor for remission. These results indicate baseline characters that related to response and those related to remission may be different for patients with schizophrenia. PMID- 24230994 TI - DSM-5 PTSD's symptom dimensions and relations with major depression's symptom dimensions in a primary care sample. AB - Existing literature indicates significant comorbidity between posttraumatic stress disorder (PTSD) and major depression. We examined whether PTSD's dysphoria and mood/cognitions factors, conceptualized by the empirically supported four factor DSM-5 PTSD models, account for PTSD's inherent relationship with depression. We hypothesized that depression's somatic and non-somatic factors would be more related to PTSD's dysphoria and mood/cognitions factors than other PTSD model factors. Further, we hypothesized that PTSD's arousal would significantly mediate relations between PTSD's dysphoria and somatic/non-somatic depression. Using 181 trauma-exposed primary care patients, confirmatory factor analyses (CFA) indicated a well-fitting DSM-5 PTSD dysphoria model, DSM-5 numbing model and two-factor depression model. Both somatic and non-somatic depression factors were more related to PTSD's dysphoria and mood/cognitions factors than to re-experiencing and avoidance factors; non-somatic depression was more related to PTSD's dysphoria than PTSD's arousal factor. PTSD's arousal did not mediate the relationship between PTSD's dysphoria and somatic/non-somatic depression. Implications are discussed. PMID- 24230995 TI - Pre-morbid alexithymia in panic disorder: a cohort study. AB - Whether alexithymia is a personality trait which increases the risk of Panic Disorder (PD) is still debated. In this prospective study, alexithymic levels were evaluated before, during and after an anxious episode. Therefore, the alexithymic levels, the presence of PD and the severity of anxious-depressive symptoms were evaluated, at intervals of about 1 month, in pregnant women, attending the Centers for Prenatal Care, using the Toronto Alexithymia Scale (TAS 20), the Primary Care Evaluation of Mental Disorders and the Hospital Anxiety and Depression Scale (HADS). Twenty-one women affected by PD and 256 healthy women (controls) were included in the study. Women who developed PD, compared to controls, showed similar TAS-20 and HADS scores during the pre-morbid phase, a significant increase of them during PD and a significant decrease after symptoms improvement, whereas no change was observed in controls. Our data suggest that in pregnant women alexithymia does not represent a personality trait that increases the risk of developing PD, and they support the hypothesis that alexithymia is a state dependent phenomenon in PD pregnant women. PMID- 24230996 TI - Characteristics of patients frequently subjected to pharmacological and mechanical restraint--a register study in three Norwegian acute psychiatric wards. AB - This retrospective study from three catchment-area-based acute psychiatric wards showed that of all the pharmacologically and mechanically restrained patients (n=373) 34 (9.1%) had been frequently restrained (6 or more times). These patients accounted for 39.2% of all restraint episodes during the two-year study period. Adjusted binary logistic regression analyses showed that the odds for being frequently restrained were 91% lower among patients above 50 years compared to those aged 18-29 years; a threefold increase (OR=3.1) for those admitted 3 times or more compared to patients with only one stay; and, finally, a threefold increase (OR=3.1) if the length of stay was 16 days or more compared to those admitted for 0-4 days. Among frequently restrained patients, males (n=15) had significantly longer stays than women (n=19), and 8 of the females had a diagnosis of personality disorder, compared to none among males. Our study showed that being frequently restrained was associated with long inpatient stay, many admissions and young age. Teasing out patient characteristics associated with the risk of being frequently restraint may contribute to reduce use of restraint by developing alternative interventions for these patients. PMID- 24230997 TI - ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment. AB - Methadone maintenance treatment is the most widely-used therapy in opioid dependence, but some patients relapse or drop out from treatment. We genotyped a genetic variant in the succinic semialdehyde dehydrogenase enzyme gene, ALDH5A1, and found that subjects carrying the T variant allele have a higher risk to be nonresponders to methadone treatment (OR=3.16; 95% CI [1.48-6.73], P=0.0024). This could be due to a reduction in the ALDH5A1 enzyme activity, that would increase endogenous gamma-hydroxbutyric acid (GHB) and gamma-aminobutyric acid (GABA) levels and therefore, inducing symptoms such as sedation and impaired pschomotor performance. These neuropsychological effects related with the reduction in enzyme activity could be responsible for a higher propensity to relapse in these genetically predisposed patients. PMID- 24230998 TI - Alcohol consumption and cognitive impairment among Korean older adults: does gender matter? AB - BACKGROUND: This study investigated gender differences in the relationship between alcohol consumption and cognitive impairment among older adults in South Korea. METHODS: Using data from the Korean Longitudinal Study of Ageing, 2,471 females and 1,657 males were analyzed separately. Cognitive impairment was measured based on the Korean version of the Mini-Mental State Exam score. Logistic regression was conducted to examine the relationship between alcohol consumption and cognitive impairment among Korean older adults. RESULTS: Multivariate analysis showed that compared to moderate drinkers, past drinkers were more likely to be cognitively impaired for women, while heavy drinkers were more likely to be cognitively impaired for men. CONCLUSIONS: Findings suggest that the relationship between alcohol consumption and cognition varies with gender. Clinicians and service providers should consider gender differences when developing strategies for the prevention and treatment of alcohol-related cognitive decline among older adults. PMID- 24230999 TI - The many faces of Artemis-deficient combined immunodeficiency - Two patients with DCLRE1C mutations and a systematic literature review of genotype-phenotype correlation. AB - Defective V(D)J recombination and DNA double-strand break (DSB) repair severely impair the development of T-lymphocytes and B-lymphocytes. Most patients manifest a severe combined immunodeficiency during infancy. We report 2 siblings with combined immunodeficiency (CID) and immunodysregulation caused by compound heterozygous Artemis mutations, including an exon 1-3 deletion generating a null allele, and a missense change (p.T71P). Skin fibroblasts demonstrated normal DSB repair by gamma-H2AX analysis, supporting the predicted hypomorphic nature of the p.T71P allele. In addition to these two patients, 12 patients with Artemis deficient CID were previously reported. All had significant morbidities including recurrent infections, autoimmunity, EBV-associated lymphoma, and carcinoma despite having hypomorphic mutants with residual Artemis expression, V(D)J recombination or DSB repair capacity. Nine patients underwent stem cell transplant and six survived, while four patients who did not receive transplant died. The progressive nature of immunodeficiency and genomic instability accounts for poor survival, and early HSCT should be considered. PMID- 24231000 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulates proliferation of HAPI microglia by affecting the Akt/GSK-3beta/cyclin D1 signaling pathway. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that induces apoptosis of neurons and a pro-inflammatory response in microglial cells. First, we found that TCDD induced proliferation of HAPI microglial cells in a dose- and time-dependent manner. Flow cytometry analysis showed that this proliferation by TCDD was due to mainly enhancing the G1 to S phase transition. Next, it was found that TCDD treatment led to up-regulation of cyclin D1, which induces cell cycle progression from G1 to S phase, in a time-dependent manner. As for molecular mechanism, we revealed that TCDD was capable of inducing Akt phosphorylation and activation, resulting in phosphorylation and inactivation of glycogen synthase kinase-3beta (GSK-3beta). Inactivated GSK-3beta attenuated proteasomal degradation of cyclin D1 by reducing Thr(286)-phosphorylated cyclin D1 levels. Moreover, inactivated GSK-3beta increased cyclin D1 gene transcription by increasing its transcription factor beta-catenin in the nucleus. Further, blockage of phosphoinositide 3-kinase/Akt kinase with their specific inhibitors, LY294002 and Akt 1/2 kinase inhibitor, significantly reduced TCDD-enhanced proliferation of HAPI microglial cells. In conclusion, TCDD stimulates proliferation of HAPI microglial cells by affecting the Akt/GSK-3beta/cyclin D1 signaling pathway. PMID- 24231001 TI - The role of the IRE1 pathway in excessive iodide- and/or fluoride-induced apoptosis in Nthy-ori 3-1 cells in vitro. AB - Excessive iodide and fluoride coexist in the groundwater in many regions, causing a potential risk to the human thyroid. To investigate the mechanism of iodide- and fluoride-induced thyroid cytotoxicity, human thyroid follicular epithelial cells (Nthy-ori 3-1) were treated with different concentrations of potassium iodide (KI), with or without sodium fluoride (NaF). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, and expression of inositol requiring enzyme 1 (IRE1) pathway-related molecules were assessed. Results showed 50 mM of KI, 1 mM of NaF, and 50 mM of KI +1 mM of NaF changed cellular morphology, decreased viability, and increased LDH leakage and apoptosis. Elevated expression of binding protein (BiP), IRE1, and C/EBP homologous protein (CHOP) mRNA and protein, as well as spliced X-box-binding protein-1 (sXBP-1) mRNA, were observed in the 1 mM NaF and 50 mM KI +1 mM NaF groups. Collectively, excessive iodide and/or fluoride is cytotoxic to the human thyroid. Although these data do not manifest iodide could induce the IRE1 pathway, the cytotoxicity followed by exposure to fluoride alone or in combination with iodide may be related to IRE1 pathway-induced apoptosis. Furthermore, exposure to the combination of excessive iodide and fluoride may cause interactive effects on thyroid cytotoxicity. PMID- 24231002 TI - General movements in healthy full term infants during the first week after birth. AB - BACKGROUND: The quality of general movements (GMs) is a widely used criterion to assess neurological dysfunction in young infants. It is unknown, however, whether the birth process influences the motor repertoire of healthy full term infants during the first week after birth. AIMS: To assess the quality of GMs and to determine the motor optimality score (OS) in healthy full term infants during the first week after birth and to evaluate the influence of the mode of delivery on GM quality. STUDY DESIGN: Thirty-three healthy full term infants born either vaginally or after caesarean section (CS) under spinal anaesthesia were video recorded in the first week after birth in order to assess GM quality and to determine OS with Prechtl's method. RESULTS: Abnormal GMs were observed mainly on the early recordings: 86% on the day of birth (day 0), 94% on day 1, and 68% on day 2. On days 5 to 7 (day 5-7) all GMs were normal (P<.001). The OSs increased significantly from median 12 on day 0 to 18 on day 5-7 (P<.001). Monotonously slow movements were frequently seen during the first days but not on day 5-7 (P<.001). GM quality and OS did not differ between infants born by vaginal delivery or after CS under spinal anaesthesia. CONCLUSIONS: Healthy full term infants often showed abnormal GM quality and lower OSs during the first week after birth, irrespective of the mode of delivery. GM quality normalised during subsequent days and was normal on day 5-7. PMID- 24231005 TI - Abdominal wall reconstruction. PMID- 24231006 TI - Case studies and evidence based nutrition. AB - The clinical nutrition case study is a neglected area of activity and publication. This may be in part because it is not regarded as a serious contributor to evidence-based nutrition (EBN). Yet it can play a valuable part in hypothesis formulation and in the cross-checking of evidence. Most of all, it is usually a point at which the operationalisation of nutrition evidence is granted best current practice status. PMID- 24231007 TI - Systematic classification of evidence for dietary refer-ence intakes for Japanese 2010 (DRIs-J 2010) in adults and future prospects of DRIs in Asian countries. AB - In Asia, the concept of dietary reference values is shifting from recommended dietary allowances (RDAs) to dietary reference intakes (DRIs). To assist Asian countries that are planning to develop or revise their own DRIs, this study summarizes the scientific literature used in the development of the latest DRIs for the Japanese (DRIs-J 2010): it aims to clarify critical issues on- and discuss future prospects for DRIs in Asia. The criteria and studies used to determine reference values in DRIs-J 2010 in adults were extracted from the DRIs J 2010 report, systematically classified, and summarized for each nutrient in tables according to the type of DRIs. The classification categories were as follows: criteria, subject ethnicity, year of publication, type of study and study design, number of subjects, and study content. In all, 184 studies were extracted and some issues in DRIs-J 2010 were clarified: 1) some nutrients were lacking in studies based on native populations; 2) only a few and relatively old studies determined tolerable upper intake levels for some nutrients; 3) with the same DRIs, there were inconsistencies among the nutrients in the study criteria. These were considered common issues when determining DRIs in other Asian countries. When establishing DRIs, these issues should be considered, in addition to population health status and country-specific needs. PMID- 24231008 TI - Salt intakes and salt reduction initiatives in Southeast Asia: a review. AB - Increased dietary sodium intake is a modifiable risk factor for cardiovascular disease. The monitoring of population sodium intake is a key part of any salt reduction intervention. However, the extent and methods used for as-sessment of sodium intake in Southeast Asia is currently unclear. This paper provides a narrative synthesis of the best available evidence regarding levels of sodium intake in six Southeast Asian countries: Indonesia, Malaysia, Philippines, Singapore, Thailand, Vietnam, and describes salt reduction measures being undertaken in these countries. Electronic databases were screened to identify relevant articles for inclusion up to 29 February 2012. Reference lists of included studies and conference proceedings were also examined. Local experts and researchers in nutrition and public health were consulted. Quality of studies was assessed using a modified version of the Downs and Black Checklist. Twenty-five studies fulfilled the inclusion criteria and were included in this review. Full texts of 19 studies including government reports were retrieved, with most studies being of good quality. In-sufficient evidence exists regarding salt intakes in Southeast Asia. Dietary data suggest that sodium intake in most SEA countries exceeded the WHO recommendation of 2 g/day. Studies are needed that estimate sodium intake using the gold standard 24-hour urinary sodium excretion. The greatest proportion of dietary sodium came from added salt and sauces. Data on children were limited. The six countries had salt reduction initiatives that differed in specificity and extent, with greater emphasis on consumer education. PMID- 24231009 TI - Shiftworking, nutrition and obesity: implications for workforce health- a systematic review. AB - BACKGROUND: Shiftworking has long been unrecognised as an occupational health hazard up until now. METHODS: Electronic databases were searched using OVID host as the main search engine for Medline, PUBMED and CINHAL during the years 1990 December 2010. Combinations of the keywords yielded 35 full papers and ab stracts, of which 16 articles were relevant. One paper was not in English, leaving 15 included in this review after final reconsideration. Studies were categorised into two main titles: studies assessing the association between shift working and obesity and/or BMI (n=8) and studies assessing the association between shift working and nu-tritional/dietary patterns (n=7). Type of study was also considered as a part of the search strategy. RESULTS: In total, one interventional, nine cross-sectional and five cohort studies were retrieved. Seven cross-sectional studies and one cohort study showed a higher BMI/obesity prevalence in shiftworks. Interventional, one cross-sectional and three cohort studies showed higher frequency of meal intake or poor nutrition quality/habits in the shift workers compared with the day-shift workers. Another cross-sectional study showed no difference between workers. CONCLUSION: In terms of obesity or high BMI, majority of cross-sectional studies indicate that shiftwork increases weight gain and the prevalence of obesity. On the other hand, half of cohort studies show higher frequency of meal intake and/or poor nutrition quality in the shift workers. Generally, it is indicated that shift working negatively impacts on health and nutritional status of workforces. PMID- 24231010 TI - Simplified malnutrition tool for Thai patients. AB - Malnutrition in hospitals often goes unrecognized. At present, no nutrition screening tool provides satisfactory re-sults in identifying nutritional risk. Most tools depend on weight and height as criteria for diagnosing malnutrition. Weight is not recorded in many patients and some tools are time-consuming. An inclusive nutrition screening form (Nutrition Alert Form, NAF) was developed and validated. NAF was modified from the original version of Subjective Global Assessment (SGA) by adding in two standard laboratory tests. The severity of the symptom and laboratory changes were scored. NAF was validated in 210 hospitalized Thai patients at Ramathibodi hospital by an experienced clinical nutritionist (physician) at Ramathibodi hospital. Cross validation was carried out between the dietitian and nurse in another 90 patients. Most of the time nurses could complete the nutrition screening in a patient within 5 minutes. One out of four patients could not be weighed on admission. The scores of 5 and 11 were selected as the cut-off scores of different malnutrition levels due to their high sensitivity, specificity and accuracy and scores of 6 to 10 were defined as moderate malnutrition. The diagnostic agreement between the dietitian and nurse for "normal to mild malnutrition", "moderate malnutrition", and "severe malnutrition" were 85%, 70% and 72%, respectively. NAF for screening of malnutrition in hospitalized Thai patients is easy to use, concise, does not require nutrition expertise and can be used whether or not body weight is taken. PMID- 24231011 TI - Development and validation of anthropometric prediction equations for estimation of body fat in Indonesian men. AB - Body composition of 292 males aged between 18 and 65 years was measured using the deuterium oxide dilution technique. Participants were divided into development (n=146) and cross-validation (n=146) groups. Stature, body weight, skinfold thickness at eight sites, girth at five sites, and bone breadth at four sites were measured and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to stature ratio (WSR) calculated. Equations were developed using multiple regression analyses with skinfolds, breadth and girth measures, BMI, and other indices as independent variables and percentage body fat (%BF) determined from deuterium dilution technique as the reference. All equations were then tested in the cross-validation group. Results from the reference method were also compared with existing prediction equations by Durnin and Womersley (1974), Davidson et al (2011), and Gurrici et al (1998). The proposed prediction equations were valid in our cross-validation samples with r=0.77- 0.86, bias 0.2-0.5%, and pure error 2.8 3.6%. The strongest was generated from skinfolds with r=0.83, SEE 3.7%, and AIC 377.2. The Durnin and Womersley (1974) and Davidson et al (2011) equations significantly (p<0.001) underestimated %BF by 1.0 and 6.9% respectively, whereas the Gurrici et al (1998) equation significantly (p<0.001) overestimated %BF by 3.3% in our cross-validation samples compared to the reference. Results suggest that the proposed prediction equations are useful in the estimation of %BF in Indonesian men. PMID- 24231012 TI - Glutamine supplementation in preterm infants receiving parenteral nutrition leads to an early improvement in liver function. AB - OBJECTIVE: The aim of study was to confirm the protective effects of parenteral glutamine supplementation on liver injury in premature infants and determine how quickly effects became evident. METHODS: We performed a double-blind, randomized, controlled clinical study to assess the effect of parenteral nutrition (PN) supplemented with glutamine in premature infants. Thirty infants from two children's centers, were randomly assigned to either a control group (Standard PN; n=15) or a glutamine-supplemented group (GlnPN; n=15). The primary endpoint was hepatic function. The secondary endpoints were total duration of PN, weight and head circumference gain, length of hospitalization, and days on a ventilator. RESULTS: The serum level of alkaline phosphatase (AKP) after parenteral nutrition for 14 days was significantly higher (p<0.05) in the control group. But in the glutamine-supplemented group, the serum concentration of aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) significantly decreased after PN for 7 days and 14 days (p<0.05), and the level of alkaline phosphatase (AKP) showed no increase. The levels of AKP and GGT were significantly different with time by group interaction. Levels of AKP was higher in control group than glutamine-supplemented group, and GGT level was lower in glutamine-supplemented group compared with controls. There were no significant differences between the groups in terms of total duration of PN, weight gain (g/d), increase in head circumference (cm/w), length of hospitalization, and duration of mechanical ventilation. CONCLUSION: The longer the duration of parenteral nutrition, the more severe hepatic dysfunction became. Parenteral glutamine supplementation suggested a hepatoprotective effect. PMID- 24231013 TI - Influence of early enteral nutrition (EEN) on insulin resistance in gastric cancer patients after surgery. AB - OBJECTIVE: To evaluate the benefits of reducing insulin resistance by early enteral nutrition (EEN) in gastric cancer patients after surgery. METHODS: Gastric cancer patients were managed to randomly accept traditional total parenteral nutrition (group A) or EEN (group B) after surgical treatment. The patients in group B were fed by tubes with 250-500 mL 5% sodium chloride and glucose injection at 24 h post-surgery, and were fed enteral nutritional emulsion with constant infusion by pump slowly increasing from 20 mL/h to 100 mL/h from 48 h, and then transiting to total enteral nutrition. Insulin sensitivity of patients was detected by Quicki method before operation and at 24 h, 48 h, 72 h, 120 h and 168 h post-surgery. RESULTS: A total of 77 patients were enrolled, with 42 patients in group A, and 35 patients in group B. Baseline characteristics, biochemical indexes and operational characteristics were well balanced between two groups. The time-insulin sensitivity curves of the two groups indicated that IR was present early (day 1 to day 7) in gastric cancer patients and was significantly different between patients who had undergone surgical treatment and those who had not. Insulin sensitivity (SI) of patients in group B were higher than patients in group A with adjusting BMI, age and SI preoperative at 72 h, 120 h and 168 h post-surgery. CONCLUSIONS: The management of EEN can alleviate insulin resistance in gastric cancer patients with surgical treatment. PMID- 24231014 TI - Early initiation of enteral nutrition improves outcomes in burn disease. AB - BACKGROUND: Burned patients have increased level of mortality, possibly due to late introduction of enteral feeding. The aim of this study was to compare the benefits and safety of very early enteral nutrition introduction compared to the normal diet among burns patients in an intensive care unit. PARTICIPANTS AND METHODS: Participants consisted of 101 patients, aged 20-76 years (mean age 48 years), 49 men and 52 women, with burns that covered more than 20% of the body. The intervention group consisted of 52 subjects fed via introduced nasojejunal probe that started within four hours after admission to the hospital. The control group consisted of fifty patients fed in standard manner per os (three standard hospital meals) immediately after the first wound dressing. RESULTS: The average decline BMI in control group was 2.27+/-0.56 kg/m2, while the average reduction in BMI in the intervention group was 1.77+/-0.38 kg/m2 (p<0.001). The largest drop of albumin concentration in the control group was 28.5%, whereas in the intervention group was 23.8%. (p<0.001). The greatest decrease of transferrin concentration in the control group was 31.1%, while the average reduction in the intervention group was 18.3%. (p<0.001). C-reactive protein values were statistically higher in control group (p<0.001). Intervention group had lower rate of complications and infection rates. CONCLUSION: Enteral nutrition in burned patients should begin within few hours of burn onset. Such approach leads to better outcomes, reduces complications, and improves nutritional profile. PMID- 24231015 TI - Effects of a nutrition support team on clinical outcomes, metabolic complications and electrolyte abnormalities in patients receiving parenteral nutrition. AB - The effectiveness of the Nutrition Support Team (NST) at Hospital Sungai Buloh, a large public hospital in Kuala Lumpur, Malaysia, in optimising parenteral nutrition (PN) has not been evaluated. To evaluate the effects of this NST in optimising patient outcomes, treatment outcomes, and adherence to biochemical monitoring guidelines, two groups of patients, those given PN before (n = 106) NST intervention and those given PN after (n=106) NST intervention, were retrospectively compared. Intervention by the NST significantly reduced metabolic abnormalities, reducing sodium abnormalities from 67% to 44% (p<0.01); potassium abnormalities from 42% to 15% (p<0.01); magnesium abnormalities from 13% to 3% (p<0.05) and phosphate abnormalities from 21% to 9% (p=0.01). Intervention by the NST also significantly reduced the incidence of hypertriglyceridemia from 68% to 45% (p=0.002) and significantly improved adherence to biochemical monitoring guidelines from 46% to 72% (p<0.01). However, the length of hospital stay, patient mortality, and duration of PN were similar in both groups. This study failed to demonstrate that the establishment of a NST gave better outcomes in terms of the common measures of effectiveness. In conclusion, although management by an NST significantly reduced metabolic abnormalities and improved adherence to biochemical monitoring guidelines, the NST did not improve patient mortality rates and length of hospital stay. PMID- 24231016 TI - Reducing effect of calcium in combination with magnesium and lactulose on body fat mass in middle-aged Japanese women. AB - BACKGROUND: It has been reported that adequate calcium intake decreases body fat and appropriate intakes of magnesium suppress the development of the metabolic syndrome. Furthermore, lactulose increases the absorption of calcium and magnesium. An optimal combination of calcium, magnesium and lactulose may therefore reduce body fat mass. METHODS: An open-label randomized controlled trial was conducted to investigate the body fat-reducing effects of a test food containing 300 mg calcium, 150 mg magnesium, and 4.0 g lactulose. Body composition parameters and blood hormone and urine mineral concentrations were measured at baseline and at 6 and 12 months thereafter. Whole-body fat mass was measured with dual-energy x-ray absorptiometry. RESULTS: Seventy-six middle-aged Japanese women (47.5+/-4.7 years) were randomized to the intake group (n=48) or the non-intake control group (n=28). At 12 months the difference in body fat mass change between the two groups (intake group - control group) was -0.8 kg (95% CI: -1.5 - 0.0 kg, p=0.046), although there were no differences in anthropometric data between the two groups. Body fat percentage at 12 months tended to be lower in the intake group, but the difference was not significant (p=0.09). CONCLUSIONS: These findings may suggest that calcium in combination with magnesium and lactulose can reduce body fat mass in middle-aged Japanese women. However, the contribution of magnesium and lactulose are unclear in this study. Further studies are needed to clarify these contributions. PMID- 24231017 TI - Effect of traditional Arabic coffee consumption on the glycemic index of Khalas dates tested in healthy and diabetic subjects. AB - The consumption of dates with coffee is common among Arabs and may affect postprandial hyperglycemia ex-cursion. The study aimed to determine the effect of coffee on the glycemic index of a common variety of dates (Khalas) tested in healthy and type 2 diabetes mellitus individuals. Study subjects were thirteen healthy volunteers (mean age: 40.2+/-6.7 years) and ten diabetic participants with a mean HbA1c of 6.6+/-(0.7%) and a mean age of 40.8+/-5.7 years. Each subject participated in five days of tests with 50 g of glucose and 50 g equivalent of available carbohydrates from the dates (with/without coffee). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min, and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. Glycemic indices were determined as ratios of the incremental areas under the response curves for the interventions. Statistical analyses were performed using the independent samples and paired t-tests. Mean+/-SE glycemic indices of the Khalas dates for the healthy individuals were 55.1+/-7.7 and 52.7+/-6.2 without and with coffee consumption, respectively. Similar values were observed for those with diabetes (53.0+/-6.0 and 41.5+/-5.4). Differences between glycemic indices of Khalas with or without coffee were not significant (p=0.124). There were no significant differences in glycemic index between the diabetic and healthy subjects (p=0.834 and p=0.202 without and with coffee respectively). In conclusion, at least in the short term, coffee does not adversely affect capillary glucose levels following Khalas dates consumption in healthy and diabetic volunteers. PMID- 24231018 TI - Impact of diet and weight loss on iron and zinc status in overweight and obese young women. AB - Young overweight women are at risk of iron and zinc deficiency. This study assessed iron, zinc and inflammatory status during a 12-month weight loss trial in young women (18-25 y; BMI >=27.5 kg/m2) randomised to a higher-protein (HP: 32% protein; 12.2 mg/day iron; 11.7 mg/day zinc) or lower-protein (LP: 20%; 9.9 mg/day; 7.6 mg/day respectively) diet with contrasting haem iron and zinc content. In completers (HP: n=21; LP: n=15), HP participants showed higher median ferritin (52.0 vs 39.0 MUg/L; p=0.021) and lower median soluble transferrin receptor-ferritin index (sTfR-F; 0.89 vs 1.05; p=0.024) although concentrations remained within normal range for both diets. Median C-reactive protein (CRP; HP: 3.54; LP: 4.63 mg/L) and hepcidin (HP: 5.70; LP: 8.25 ng/mL) were not elevated at baseline, and no longitudinal between-diet differences were observed for zinc and CRP. Compared to those with <5% weight loss, HP participants losing >=10% weight showed lower median sTfR-F (0.76 vs 1.03; p=0.019) at six months. Impact of >=10% weight loss on iron was more apparent in LP participants who exhibited greater mean serum iron (20.0 vs 13.5 MUmol/L; p=0.002), transferrin saturation (29.8% vs 19.4%; p=0.001) and lower sTfR (1.24 vs 1.92 mg/L; p=0.034) at 12 months. Results show normal iron and zinc status can be maintained during 12 months of energy restriction. In the absence of elevated baseline inflammation and hepcidin, a more favourable iron profile in those with >=10% weight loss may reflect stronger compliance or the potential influence of iron regulatory mechanisms unrelated to inflammatory hepcidin reduction. PMID- 24231019 TI - Relationship between skipping breakfast and bone mineral density in young Japanese women. AB - BACK GROUND AND AIMS: It is well known that insufficient nutrient intake leads to poor bone status. To find a simple evaluation method for prevention of nutrition intake disorder, a cross-sectional study with 275 healthy Japanese female students aged 19-25 was conducted. METHODS: Anthropometric parameters, bone mineral density (BMD) at lumbar and total hip, bone metabolic markers and physical activity were measured in study participants and the frequency of skipping meals (breakfast, lunch, supper), and absolute values for nutrient intakes were assessed using a Diet History Questionnaire. RESULTS: The frequency of skipping breakfast significantly correlate to total energy intake (rho= 0.276, p<0.001). BMI, total intake of energy, intake of protein, intake of phosphate, and energy expenditure positively correlated significantly to BMD at lumbar and total hip (p<0.05) using simple linear regression. BMI (regression coefficient (b))=0.088, p<0.001), bone alkaline phosphatase (b= -0.050, p=0.012), total energy expenditure (b=0.019, p<0.001), and frequency of skipping breakfast (b= -0.018, p=0.048) were independent risk factors for lower total hip BMD by multiple regression analysis. The total hip BMD in participants who skipped breakfast three or more times was significantly lower than in those who did not skip breakfast (p=0.007). CONCLUSIONS: In conclusion, managing the frequency of skipping breakfast and reducing it to <3 times per week may be beneficial for the maintenance of bone health in younger women. PMID- 24231020 TI - Prevalence and determinants of hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province in China. AB - This study investigated the prevalence and determinants of hyperuricemia in Chinese type 2 diabetes mellitus (T2DM) patients with central obesity. A multicentric hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. At each hospital, Chinese T2DM patients with central obesity who were aged over 20 years, whose serum uric acid levels were measured, and who had lived in Guangdong Province for >=1 year, were recruited. Hyperuricemia was defined as serum uric acid >420 MUmol/L in men and >360 MUmol/L in women. Binary logistic regression was used to assess associated risk factors for hyperu-ricemia. A total of 2,917 T2DM patients with central obesity took part. The overall prevalence of hyperuricemia was 32.6% (36.1% for women, 28.4% for men). Binary logistic regression analyses demonstrated that women (OR: 1.576; 95% confidence interval (CI): 1.231, 2.018), high BMI (OR: 1.228; 95% CI: 1.094, 1.379), waist cir-cumference (OR: 1.135; 95% CI: 1.009, 1.276), hypertension (OR: 1.603; 95% CI: 1.263, 2.035), high total cho-lesterol (OR: 1.133; 95% CI: 1.002, 1.281), triglycerides (OR: 1.134; 95% CI: 1.069, 1.203), low HDL-cholesterol (OR: 0.820; 95% CI: 0.677, 0.995) and low estimated glomerular filtration rate (OR: 0.840; 95% CI: 0.815, 0.866) were risk factors associated with hyperuricemia. Hyperuricemia is prevalent in Chinese T2DM patients with central obesity and is significantly positively associated with women, cardiovascular risk factors such as obesity, hypertension and dyslipidemia, and low eGFR. PMID- 24231021 TI - Leisure time physical activities and dietary quality of the general and indigenous Taiwanese populations are associated with fat distribution and sarcopenia. AB - Indigenous peoples are at greater risk of obesity-related health problems for various reasons. These have been explored in the adulthood (>=19 yrs) section of the nationally-representative Nutrition and Health Survey in Taiwan (NAHSIT) for 2005-2008 in Indigenous mountain-dwelling (IndT) (n=226) and general (mainly Han Chinese) (GenT) (n=1486) Taiwanese. Physical activity, BMI, fat distribution (waist circum-ference (WC) and triceps skinfold (TSF)) and mid arm muscle circumference (MAMC) have been com-pared. Leisure-time physical activities (LTPA) were assigned metabolic equivalents (METs). Comparisons were made by ethnicity locality. Indigenous men and women were 3.81 and 5.47 times more obese (WHO criteria BMI>=30 kg/m2) than the GenT, respectively. Some 55% of the IndT and 34% of the GenT reported no LTPA. All LTPA types were less evident in the IndT. Multivaiable adjusted ORs (95% CIs) against inactivity as referent were, for sarcopenic MAMC, in Indigenes with MVI-LTPA 0.13 (0.03-0.67) and in the GenT 0.61 (0.37-1.01); in the GenT with LTPA for BMI >=30 kg/m2 and obese TSF, they were 0.53 (0.31-0.91) and 0.77 (0.60-0.98), respectively. Without dietary quality adjustment, the sarcopenia risk in GenT with LTPA was significant (OR=0.60, 95% CI: 0.37-0.97). Having adjusted for dietary quality, the significance disappeared. Less sarcopenia was found with ambulation in the GenT (OR=2.07, 95% CI: 1.26-3.43). More over-fatness in an IndT than GenT is associated with less LTPA. LTPA reduces sarcope-nic risk irrespective of ethnicity, is partly dependent on diet, and reduces obesity indices in the GenT. PMID- 24231022 TI - Prevalence and correlates of zinc deficiency in pregnant Vietnamese women in Ho Chi Minh City. AB - BACKGROUND: Although Vietnam is a region with a plant-based diet that has a high zinc deficiency, epidemiological data showing how this affects pregnant women are limited. This study explores the prevalence of zinc deficiency and possible correlates in pregnant Vietnamese women in Ho Chi Minh City. METHODS: This was a cross-sectional study conducted at a general hospital in Ho Chi Minh City, Vietnam. All pregnant women who came to their first antenatal care visit from November 2011 to June 2012 were recruited. Those taking a vitamin and/or mineral supplement were excluded. Serum zinc concentrations, determined by a standard colorimetric method, of 10.7 MUmol/L-17.5 MUmol/L (70.0 g/dL-114 g/dL) were classified as normal and under 10.7 MUmol/L (70.0 g/dL) as zinc deficient. RESULTS: In total, 254 pregnant women were invited and 107 (42%) participated. The mean age of participants was 29 years, and mean gestational age was 10 weeks. Median zinc concentration in serum was 13.6 MUmol/L, and the prevalence of zinc deficiency was 29% (95% CI=21%-39%). The daily intake of a milk product supplement was the only significant correlate of zinc deficiency of the items investigated (adjusted OR=0.40, 95% CI=0.16-0.99, p=0.049). DISCUSSION: This is the first study reporting that more than 25% of pregnant Vietnamese women in Ho Chi Minh City are zinc deficient. Further academic and clinical input is needed to confirm the scale of this neglected issue and to investigate the potential of milk product supplementation in this population. PMID- 24231023 TI - Evaluating dietary quality in diabetes by the Healthy Eating Index. AB - Diabetes and diabetes-induced complications is a rising health concern in Northern Cyprus. Of the adult population in Northern Cyprus, 12.2% has diabetes and 90% of all individuals suffering from cardiovascular disease are people with diabetes. The aim of this study was to evaluate nutritional habits of people with diabetes in Northern Cyprus in order to make the necessary recommendations to improve their eating habits to prevent diabetes-induced complications. We used the Healthy Eating Index (HEI) to evaluate dietary quality of people with diabetes in Northern Cyprus based on their 24-hour food intake. A total of 200 participants with diabetes were selected randomly from the out-patient clinic of Dr. Burhan Nalbantoglu central hospital in Nicosia. Individuals were asked to complete a questionnaire to determine their 24-hour food intake and frequency of intake of various food substances. The mean HEI score for the subjects with diabetes was 58.8. The HEI component scores for saturated fat, vegetables, dairy products and meat consumption were less than 5, whereas average scores for fat, cholesterol, fruits, grains, and sodium consumption were more than 5. The meat component of the HEI had the lowest mean score (3.3). There was statistical significance between male and female subjects regarding the HEI scores for meat and nutrient variety intake. In conclusion, the results of the present study suggest that subjects with diabetes in Northern Cyprus should improve their diet by decreasing their intake of saturated fat and by increasing their intake of vegetables, meat and milk. PMID- 24231025 TI - Cognitive impairment and limited dietary diversity or physical inactivity are conjoint precursors of incident diabetes more so in elderly women than men. AB - OBJECTIVES: To establish whether elderly people with impaired cognition are at greater risk for the de-velopment of type 2 diabetes. DESIGN: Prospective population-based cohort study. SETTING: The El-derly Nutrition and Health Survey in Taiwan (NAHSIT Elderly). PARTICIPANTS: One thousand and four hundred ninety three diabetes-free people >=65 years were followed for incident diabetes in relation to cognitive status for up to 8 years. MEASUREMENTS: The association between cognitive impairment and diabetes incidence was analyzed with Cox proportional hazards models with exclusion of people who had diabetes within one year of cognitive function assessments. RESULTS: Cognitively-impaired women, but not men, had increased diabetes incidence density (DID). Age, gender, ethnicity and personal behavior adjusted hazard ratios (HR) and 95% confidence intervals (CI) for type 2 diabetes with normal cognition as referent were 2.43 (95% CI: 1.27-4.63) for women and 1.55 (95% CI: 0.48-5.07) for men. These gender differences and the HR significances remained with adjustments for age, ethnicity, financial status, dietary quality as a dietary diversity score, physical function, physical activity, fasting glucose, indices of body composition, body mass index, waist circumference, mid-arm muscle circumference, perceived and mental health status. There were extensive significant interactions with the covariates in women. CONCLUSION: Cognitive impairment in later life is associated with greater risk of type 2 diabetes in women and considerable potential risk enhancement. PMID- 24231024 TI - Associations of body mass index with incident hypertension in American white, American black and Chinese Asian adults in early and middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Atherosclerosis Risk in Communities (ARIC) study and the People's Republic of China (PRC) study. AB - The association of body mass index (BMI) with blood pressure may be stronger in Asian than non-Asian populations, however, longitudinal studies with direct comparisons between ethnicities are lacking. We compared the relationship of BMI with incident hypertension over approximately 9.5 years of follow-up in young (24 39 years) and middle-aged (45-64 years) Chinese Asians (n=5354), American Blacks (n=6076) and American Whites (n=13451). We estimated risk differences using logistic regression models and calculated adjusted incidences and incidence differences. To facilitate comparisons across ethnicities, standardized estimates were calculated using mean covariate values for age, sex, smoking, education and field center, and included the quadratic terms for BMI and age. Weighted least squares regression models with were constructed to summarize ethnic-specific incidence differences across BMI. Wald statistics and p-values were calculated based on chi-square distributions. The association of BMI with the incidence difference for hypertension was steeper in Chinese (p<0.05) than in American populations during young and middle-adulthood. For example, at a BMI of 25 vs 21 kg/m2 the adjusted incidence differences per 1000 persons (95% CI) in young adults with a BMI of 25 vs those with a BMI of 21 was 83 (36- 130) for Chinese, 50 (26-74) for Blacks and 30 (12-48) for Whites; among middle-aged adults it was 137 (77-198) for Chinese, 49 (9-88) for Blacks and 54 (38-69) for Whites. Whether hypertension carries the same level of risk of stroke or cardiovascular disease across national or ethnic groups remains uncertain. PMID- 24231026 TI - Effects of gamma-glutamyl carboxylase gene polymorphism (R325Q) on the association between dietary vitamin K intake and gamma-carboxylation of osteocalcin in young adults. AB - INTRODUCTION: It has been demonstrated that single nucleotide polymorphism (SNP) (R325Q, 974G>A) in the gamma-glutamyl carboxylase (GGCX) gene is associated with the bone mineral density (BMD). In the present study, we investigated the effect of GGCX polymorphism (974G>A) on the correlations among the vitamin K in-take, level of serum vitamin K, and ratio of undercarboxylated osteocalcin (ucOC) to intact osteocalcin (OC) in healthy young Japanese subjects. METHODS: Healthy young adult subjects (n=189) were genotyped for the poly-morphism, and we measured the levels of serum vitamin K, intact OC, ucOC, and dietary nutrient intakes. RESULTS: Dietary vitamin K intake from vegetables was significantly correlated with the level of serum phylloquinone (PK), and vitamin K intake from fermented beans, natto, was also significantly correlated with the level of serum menaquinone-7 (MK-7). Moreover, the total dietary vitamin K intake showed a significant negative correlation with the ratio of ucOC to intact OC. Interestingly, on grouping by the GGCX genotype, there was a significant interaction between the ratio of ucOC to intact OC with vitamin K intake in homozygotes (GG-type) and heterozygotes (GA-type) (p<0.001). These results suggest that an adequate nutritional strategy is necessary for people with high risk genotypes (GG- or GA-type). CONCLUSIONS: We demonstrated the effects of SNP (974G>A) in the GGCX gene on the correlation between dietary vitamin K intake and gamma-carboxylation of serum OC. Our data may be useful for planning strategies to prevent osteoporosis. PMID- 24231027 TI - CSPEN guidelines for nutrition support in neonates. AB - In the last few decades, there has been a significant increase in survival rate of preterm infants, especially very low birth weight infants. The nutrition problems have become particularly relevant in neonates, and nutrition support is usually required for preterm infants and most sick term infants. The actual amount of nutrition must be calculated (not estimated) in neonates. The goals of nutrition support are to maintain development and growth while avoiding nutrition related complications. Nutrition requirements (enteral nutrition and parenteral nutrition) should be adjusted according to different weights and gestational age. Parenteral nutrition (PN), which allows the infant's requirements for growth and development to be met, is indicated in infants for whom feeding via the enteral route is impossible, inadequate, or hazardous. Enteral nutrition (EN) should be gradually introduced and should replace PN as quickly as possible in order to minimize any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. Optimal nutrition care of the preterm infant offers the opportunity to improve outcomes for children. This guideline aims to provide proposed advisable ranges for nutrient intakes in neonates. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate. PMID- 24231028 TI - Implausible results in human nutrition research. PMID- 24231029 TI - Human exposure to endotoxins and fecal indicators originating from water features. AB - Exposure to contaminated aerosols and water originating from water features may pose public health risks. Endotoxins in air and water and fecal bacteria in water of water features were measured as markers for exposure to microbial cell debris and enteric pathogens, respectively. Information was collected about wind direction, wind force, distance to the water feature, the height of the water feature and the tangibility of water spray. The mean concentration of endotoxins in air nearby and in water of 31 water features was 10 endotoxin units (EU)/m(3) (Geometric Mean (GM), range 0-85.5 EU/m(3) air) and 773 EU/mL (GM, range 9-18,170 EU/mL water), respectively. Such mean concentrations may be associated with respiratory health effects. The water quality of 26 of 88 water features was poor when compared to requirements for recreational water in the Bathing Water Directive 2006/7/EC. Concentrations greater than 1000 colony forming units (cfu) Escherichia coli per 100 mL and greater than 400 cfu intestinal enterococci per 100 mL increase the probability of acquiring gastrointestinal health complaints. Regression analyses showed that the endotoxin concentration in air was significantly influenced by the concentration of endotoxin in water, the distance to the water feature and the tangibility of water spray. Exposure to air and water near water features was shown to lead to exposure to endotoxins and fecal bacteria. The potential health risks resulting from such exposure to water features may be estimated by a quantitative microbial risk assessment (QMRA), however, such QMRA would require quantitative data on pathogen concentrations, exposure volumes and dose-response relationships. The present study provides estimates for aerosolisation ratios that can be used as input for QMRA to quantify exposure and to determine infection risks from exposure to water features. PMID- 24231030 TI - Biofouling of reverse-osmosis membranes during tertiary wastewater desalination: microbial community composition. AB - Reverse-osmosis (RO) desalination is frequently used for the production of high quality water from tertiary treated wastewater (TTWW). However, the RO desalination process is often hampered by biofouling, including membrane conditioning, microbial adhesion, and biofilm growth. The vast majority of biofilm exploration concentrated on the role of bacteria in biofouling neglecting additional microbial contributors, i.e., fungi and archaea. To better understand the RO biofouling process, bacterial, archaeal and fungal diversity was characterized in a laboratory-scale RO desalination plant exploring the TTWW (RO feed), the RO membrane and the RO feed tube biofilms. We sequenced 77,400 fragments of the ribosome small subunit-encoding gene (16S and 18S rRNA) to identify the microbial community members in these matrices. Our results suggest that the bacterial, archaeal but not fungal community significantly differ from the RO membrane biofouling layer to the feedwater and tube biofilm (P < 0.01). Moreover, the RO membrane supported a more diverse community compared to the communities monitored in the feedwater and the biofilm attached to the RO feedwater tube. The tube biofilm was dominated by Actinobacteria (91.2 +/- 4.6%), while the Proteobacteria phylum dominated the feedwater and RO membrane (at relative abundance of 92.3 +/- 4.4% and 71.5 +/- 8.3%, respectively), albeit comprising different members. The archaea communities were dominated by Crenarchaeota (53.0 +/- 6.9%, 32.5 +/- 7.2% and 69%, respectively) and Euryarchaeota (43.3 +/- 6.3%, 23.2 +/- 4.8% and 24%, respectively) in all three matrices, though the communities' composition differed. But the fungal communities composition was similar in all matrices, dominated by Ascomycota (97.6 +/- 2.7%). Our results suggest that the RO membrane is a selective surface, supporting unique bacterial, and to a lesser extent archaeal communities, yet it does not select for a fungal community. PMID- 24231031 TI - Modeling Escherichia coli removal in constructed wetlands under pulse loading. AB - Manure-borne pathogens are a threat to water quality and have resulted in disease outbreaks globally. Land application of livestock manure to croplands may result in pathogen transport through surface runoff and tile drains, eventually entering water bodies such as rivers and wetlands. The goal of this study was to develop a robust model for estimating the pathogen removal in surface flow wetlands under pulse loading conditions. A new modeling approach was used to describe Escherichia coli removal in pulse-loaded constructed wetlands using adaptive neuro-fuzzy inference systems (ANFIS). Several ANFIS models were developed and validated using experimental data under pulse loading over two seasons (winter and summer). In addition to ANFIS, a mechanistic fecal coliform removal model was validated using the same sets of experimental data. The results showed that the ANFIS model significantly improved the ability to describe the dynamics of E. coli removal under pulse loading. The mechanistic model performed poorly as demonstrated by lower coefficient of determination and higher root mean squared error compared to the ANFIS models. The E. coli concentrations corresponding to the inflection points on the tracer study were keys to improving the predictability of the E. coli removal model. PMID- 24231032 TI - Towards integrating positron emission tomography for work-up of patients with Sjogren's syndrome and associated lymphomas. PMID- 24231033 TI - Food-derived bioactive peptides--a new paradigm. AB - Food-derived bioactive peptides are regarded as important modulators of several physiological processes occurring both systemically and locally within the gastrointestinal tract (GIT). However, the concentrations of food-derived bioactive peptides in the GIT, and therefore attendant physiological effects, are likely to be highly variable given the wide variation in the type and amount of dietary protein consumed either during the day or on a day-to-day basis. In contrast, gut endogenous proteins (e.g. cell proteins, mucin, serum albumin and digestive enzymes) are a consistent and significant potential source of peptides for the GIT. With up to 80% of gut endogenous proteins being digested in the GIT, it is possible that a wide range of peptides is generated, but until now the significance of the gut endogenous proteins as a source of bioactive peptides has not been considered. A hypothesis is promulgated that the gut endogenous proteins may have a hidden role as a consistent and quantitatively important source of bioactive peptides in the GIT. PMID- 24231034 TI - Evaluation of the safety and usability of touch gestures in operating in-vehicle information systems with visual occlusion. AB - Nowadays, many automobile manufacturers are interested in applying the touch gestures that are used in smart phones to operate their in-vehicle information systems (IVISs). In this study, an experiment was performed to verify the applicability of touch gestures in the operation of IVISs from the viewpoints of both driving safety and usability. In the experiment, two devices were used: one was the Apple iPad, with which various touch gestures such as flicking, panning, and pinching were enabled; the other was the SK EnNavi, which only allowed tapping touch gestures. The participants performed the touch operations using the two devices under visually occluded situations, which is a well-known technique for estimating load of visual attention while driving. In scrolling through a list, the flicking gestures required more time than the tapping gestures. Interestingly, both the flicking and simple tapping gestures required slightly higher visual attention. In moving a map, the average time taken per operation and the visual attention load required for the panning gestures did not differ from those of the simple tapping gestures that are used in existing car navigation systems. In zooming in/out of a map, the average time taken per pinching gesture was similar to that of the tapping gesture but required higher visual attention. Moreover, pinching gestures at a display angle of 75 degrees required that the participants severely bend their wrists. Because the display angles of many car navigation systems tends to be more than 75 degrees , pinching gestures can cause severe fatigue on users' wrists. Furthermore, contrary to participants' evaluation of other gestures, several participants answered that the pinching gesture was not necessary when operating IVISs. It was found that the panning gesture is the only touch gesture that can be used without negative consequences when operating IVISs while driving. The flicking gesture is likely to be used if the screen moving speed is slower or if the car is in heavy traffic. However, the pinching gesture is not an appropriate method of operating IVISs while driving in the various scenarios examined in this study. PMID- 24231035 TI - Nitrogen regulation of transpiration controls mass-flow acquisition of nutrients. AB - Transpiration may enhance mass-flow of nutrients to roots, especially in low nutrient soils or where the root system is not extensively developed. Previous work suggested that nitrogen (N) may regulate mass-flow of nutrients. Experiments were conducted to determine whether N regulates water fluxes, and whether this regulation has a functional role in controlling the mass-flow of nutrients to roots. Phaseolus vulgaris were grown in troughs designed to create an N availability gradient by restricting roots from intercepting a slow-release N source, which was placed at one of six distances behind a 25 MUm mesh from which nutrients could move by diffusion or mass-flow (termed 'mass-flow' treatment). Control plants had the N source supplied directly to their root zone so that N was available through interception, mass-flow, and diffusion (termed 'interception' treatment). 'Mass-flow' plants closest to the N source exhibited 2.9-fold higher transpiration (E), 2.6-fold higher stomatal conductance (gs), 1.2 fold higher intercellular [CO2] (Ci), and 3.4-fold lower water use efficiency than 'interception' plants, despite comparable values of photosynthetic rate (A). E, gs, and Ci first increased and then decreased with increasing distance from the N source to values even lower than those of 'interception' plants. 'Mass flow' plants accumulated phosphorus and potassium, and had maximum concentrations at 10mm from the N source. Overall, N availability regulated transpiration-driven mass-flow of nutrients from substrate zones that were inaccessible to roots. Thus when water is available, mass-flow may partially substitute for root density in providing access to nutrients without incurring the costs of root extension, although the efficacy of mass-flow also depends on soil nutrient retention and hydraulic properties. PMID- 24231036 TI - Rapid maxillary expansion in growing patients: correspondence between 3 dimensional airway changes and polysomnography. AB - OBJECTIVES: The aim of the present prospective study was to investigate the effects of rapid maxillary expansion on the airway correlating airway volumes computed on cone beam computed tomography and polysomnography evaluation of oxygen saturation and apnea/hypopnea index. METHODS: The study group comprised 14 caucasian patients (mean age 7.1 +/- 0.6 years) undergone to rapid maxillary expansion with Haas type expander banded on second deciduous upper molars. Cone beam computed tomography scans and polysomnography exams were collected before placing the appliance (T0) and after 12 months (T1). Landmarks localization and airway semiautomatic segmentation on cone beam computed tomography scans allowed airway volume computing and measurements. RESULTS: Increases of total airway volume, oxygen saturation and apnea/hypopnea index were statistically significant. No correlation was found among total airway volume, oxygen saturation and apnea/hypopnea index changes between the examined timepoints. CONCLUSIONS: Computing airway volume on cone beam computed tomography allow to measure the amount of air that flows through nasal cavity, nasopharynx and oropharynx while oxygen saturation and apnea/hypopnea index could give information about functional parameters. In the present study all three variables investigated showed statistically significant differences between T0 and T1 but no correlation was found between increases of the different variables tested. PMID- 24231037 TI - Synchronization stability and firing transitions in two types of class I neuronal networks with short-term plasticity. AB - This paper investigates synchronization stability and firing transition in two types of the modified canonical class I neuronal networks, where the short-term plasticity of synapse is introduced. We mainly consider both unidirectional chain and global coupling configurations. Previous studies have shown that the coupled class I neurons can spontaneously de-synchronize. Presently, the short-term plasticity of synapse is considered to check the universality of this phenomenon. Based on the theoretical analysis and numerical simulation, it is shown that unidirectionally chain coupled class I neurons can realize synchronization, whereas bidirectionally coupled chain neurons cannot synchronize, and globally coupled class I neurons de-synchronize. Furthermore, the dynamics of coupled neurons with different firing modes are also studied in numerical simulations, and interesting transitions of different firing modes can be induced by the short term plasticity. The obtained results can be helpful to further understand important effects of the short-term synaptic plasticity on realistic neuronal systems. PMID- 24231038 TI - Scene construction in developmental amnesia: an fMRI study. AB - Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients' scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes. PMID- 24231039 TI - Electromyographic latency of postural evoked responses from the leg muscles during EquiTest Computerised Dynamic Posturography: Reference data on healthy subjects. AB - No normative data are available for the latencies of the EMG signals from the ankle muscles in response to sudden sagittal tilt (toes-UP or toes-DOWN) or shift (shift-FOR or shift-BACK) of the support surface during standing. In this study the postural evoked response (PER) paradigm on the EquiTestTM force platform was applied to 31 healthy adults (18 women and 13 men; mean age 29 years). The EMG latencies (PEREMG) were computed both through the standard manual procedure and through a specially designed automated algorithm. The manually computed PEREMG onset yielded a 95% tolerance interval between 82ms and 148ms after toes-UP perturbation, between 93ms and 182ms after toes-DOWN perturbation, between 67ms and 107ms after shift-BACK perturbation, and between 73ms and 113ms after shift FOR perturbation. When comparing the two methods, paired t-tests showed no significant mean difference (Bonferroni-adjusted p-values ranged from 0.440 to 1.000) and all Bland-Altman plots included zero difference within the limits of agreement. Therefore, the manual and the automated methods appear to be sufficiently consistent. These results foster the clinical application of PEREMG testing on the EquiTest platform. PMID- 24231040 TI - The good, bad, and ugly of online recruitment of parents for health-related focus groups: lessons learned. AB - BACKGROUND: We describe our experiences with identifying and recruiting Ontario parents through the Internet, primarily, as well as other modes, for participation in focus groups about adding the influenza vaccine to school-based immunization programs. OBJECTIVE: Our objectives were to assess participation rates with and without incentives and software restrictions. We also plan to examine study response patterns of unique and multiple submissions and assess efficiency of each online advertising mode. METHODS: We used social media, deal forum websites, online classified ads, conventional mass media, and email lists to invite parents of school-aged children from Ontario, Canada to complete an online questionnaire to determine eligibility for focus groups. We compared responses and paradata when an incentive was provided and there were no software restrictions to the questionnaire (Period 1) to a period when only a single submission per Internet protocol (IP) address (ie, software restrictions invoked) was permitted and no incentive was provided (Period 2). We also compared the median time to complete a questionnaire, response patterns, and percentage of missing data between questionnaires classified as multiple submissions from the same Internet protocol (IP) address or email versus unique submissions. Efficiency was calculated as the total number of hours study personnel devoted to an advertising mode divided by the resultant number of unique eligible completed questionnaires . RESULTS: Of 1346 submitted questionnaires, 223 (16.6%) were incomplete and 34 (2.52%) did not meet the initial eligibility criteria. Of the remaining 1089 questionnaires, 246 (22.6%) were not from Ontario based on IP address and postal code, and 469 (43.1%) were submitted from the same IP address or email address (multiple submissions). In Period 2 vs Period 1, a larger proportion of questionnaires were submitted from Ontario (92.8%, 141/152 vs 75.1%, 702/937, P<.001), and a smaller proportion of same IP addresses (7.9%, 12/152 vs 47.1%, 441/937, P<.001) were received. Compared to those who made unique submissions, those who made multiple submissions spent less time per questionnaire (166 vs 215 seconds, P<.001), and had a higher percentage of missing data among their responses (15.0% vs 7.6%, P=.004). Advertisements posted on RedFlagDeals were the most efficient for recruitment (0.03 hours of staff time per questionnaire), whereas those placed on Twitter were the least efficient (3.64 hours of staff time per questionnaire). CONCLUSIONS: Using multiple online advertising strategies was effective for recruiting a large sample of participants in a relatively short period time with minimal resources. However, risks such as multiple submissions and potentially fraudulent information need to be considered. In our study, these problems were associated with providing an incentive for responding, and could have been partially avoided by activating restrictive software features for online questionnaires. PMID- 24231041 TI - The presence of polychlorinated biphenyls in yellow pigment products in China with emphasis on 3,3'-dichlorobiphenyl (PCB 11). AB - A non-Aroclor PCB congener, 3,3'-dichlorobiphenyl (PCB 11) has recently attracted wide concerns because of its environmental ubiquity and specific sources potentially associated with yellow pigment production. In order to investigate PCB 11 and other PCBs in the yellow pigment products, 24 yellow pigment samples were collected from three different manufacturing plants in China. ?20PCBs and PCB 11 were in the range of 50.7-9.19*10(5) ng g(-1) and 41.7-9.18*10(5) ng g( 1), respectively, which was much higher than those reported in previous study. The corresponding TEQ values ranged between 0.16 and 4.21*10(3) ng WHO2005-TEQ kg(-1). The contribution of PCB 11 to ?20PCBs reached up to 85.5% (median value) followed by PCB 28, PCB 77, and PCB 52 with contributions of 10.5%, 6.70%, and 5.40%, respectively. Significant differences were observed for PCB 11 concentrations among the different types of yellow pigment from the same plant and among the same sample types from different plants. The PCB 11 concentrations in diarylide yellow pigments produced from 3,3'-dichlorbenzidine were the highest in all the samples. It demonstrates that yellow pigment is a significant source not only for the widespread pollution of PCB 11 but also for other PCBs, especially for the lower chlorinated congeners. PMID- 24231042 TI - A comprehensive substance flow analysis of a municipal wastewater and sludge treatment plant. AB - The fate of total organic carbon, 32 elements (Al, Ag, As, Ba, Be, Br, Ca, Cd, Cl, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, N, Na, Ni, P, Pb, S, Sb, Se, Sn, Sr, Ti, V, and Zn) and 4 groups of organic pollutants (linear alkylbenzene sulfonates, bis(2-ethylhexyl)phthalate, polychlorinated biphenyl and polycyclic aromatic hydrocarbons) in a conventional wastewater treatment plant were assessed. Mass balances showed reasonable closures for most of the elements. However, gaseous emissions were accompanied by large uncertainties and show the limitation of mass balance based substance flow analysis. Based on the assessment, it is evident that both inorganic and organic elements accumulated in the sewage sludge, with the exception of elements that are highly soluble or degradable by wastewater and sludge treatment processes. The majority of metals and metalloids were further accumulated in the incineration ash, while the organic pollutants were effectively destroyed by both biological and thermal processes. Side streams from the sludge treatment process (dewatering and incineration) back to the wastewater treatment represented less than 1% of the total volume entering the wastewater treatment processes, but represented significant substance flows. In contrast, the contribution by spent water from the flue gas treatment process was almost negligible. Screening of human and eco toxicity by applying the consensus-based environmental impact assessment method USEtox addressing 15 inorganic constituents showed that removal of inorganic constituents by the wastewater treatment plant reduced the toxic impact potential by 87-92%. PMID- 24231043 TI - Bisphenol A promotes dendritic morphogenesis of hippocampal neurons through estrogen receptor-mediated ERK1/2 signal pathway. AB - Bisphenol A (BPA), an environmental endocrine disruptor, has attracted increasing attention to its adverse effects on brain developmental process. The previous study indicated that BPA rapidly increased motility and density of dendritic filopodia and enhanced the phosphorylation of N-methyl-d-aspartate (NMDA) receptor subunit NR2B in cultured hippocampal neurons within 30min. The purpose of the present study was further to investigate the effects of BPA for 24h on dendritic morphogenesis and the underlying mechanisms. After cultured for 5d in vitro, the hippocampal neurons from 24h-old rat were infected by AdV-EGFP to indicate time-lapse imaging of living neurons. The results demonstrated that the exposure of the cultured hippocampal neurons to BPA (10, 100nM) or 17beta estradiol (17beta-E2, 10nM) for 24h significantly promoted dendritic development, as evidenced by the increased total length of dendrite and the enhanced motility and density of dendritic filopodia. However, these changes were suppressed by an ERs antagonist, ICI182,780, a non-competitive NMDA receptor antagonist, MK-801, and a mitogen-activated ERK1/2-activating kinase (MEK1/2) inhibitor, U0126. Meanwhile, the increased F-actin (filamentous actin) induced by BPA (100nM) was also completely eliminated by these blockers. Furthermore, the result of western blot analyses showed that, the exposure of the cultures to BPA or 17beta-E2 for 24h promoted the expression of Rac1/Cdc42 but inhibited that of RhoA, suggesting Rac1 (Ras related C3 botulinum toxinsubstrate 1)/Cdc42 (cell divisioncycle 42) and RhoA (Ras homologous A), the Rho family of small GTPases, were involved in BPA- or 17beta-E2-induced changes in the dendritic morphogenesis of neurons. These BPA- or 17beta-E2-induced effects were completely blocked by ICI182,780, and were partially suppressed by U0126. These results reveal that, similar to 17beta-E2, BPA exerts its effects on dendritic morphogenesis by eliciting both nuclear actions and extranuclear-initiated actions that are integrated to influence the development of dendrite in hippocampal neurons. PMID- 24231044 TI - Coupling of solar photoelectro-Fenton with a BDD anode and solar heterogeneous photocatalysis for the mineralization of the herbicide atrazine. AB - Here, the synergetic effect of coupling solar photoelectro-Fenton (SPEF) and solar heterogeneous photocatalysis (SPC) on the mineralization of 200mL of a 20mg L(-1) atrazine solution, prepared from the commercial herbicide Gesaprim, at pH 3.0 was studied. Uniform, homogeneous and adherent anatase-TiO2 films onto glass spheres of 5mm diameter were prepared by the sol-gel dip-coating method and used as catalyst for SPC. However, this procedure yielded a poor removal of the substrate because of the low oxidation ability of positive holes and OH formed at the catalyst surface to destroy it. Atrazine decay was improved using anodic oxidation (AO), electro-Fenton (EF), SPEF and coupled SPEF-SPC at 100mA. The electrolytic cell contained a boron-doped diamond (BDD) anode and H2O2 was generated at a BDD cathode fed with an air flow. The removal and mineralization of atrazine increased when more oxidizing agents were generated in the sequence AO6-8000 Da) conjugated with ibuprofen showing that degradation and drug release are simultaneous. By considering the free and conjugated ibuprofen, 13% of the drug is released in 3 months. In vitro, ibuprofen-loaded MS inhibited the synthesis of prostaglandin E2 in articular cartilage and capsule explants challenged with lipopolysaccharides. Covalent attachment of ibuprofen to PEG-hydrogel MS suppresses the burst release and allows a slow drug delivery for months and the cyclooxygenase-inhibition property of regenerated ibuprofen is preserved. PMID- 24231052 TI - Safety and effectiveness of drug-eluting stents versus bare-metal stents in elderly patients with small coronary vessel disease. AB - BACKGROUND: Drug-eluting stents (DES) are more effective than bare-metal stents (BMS) in small coronary vessel disease. Whether this is true in elderly patients, it is unclear, as frailty and a high rate of comorbidities could increase the rate of DES-related complications. AIMS: To assess procedural and long-term clinical outcomes of elderly patients with small vessel disease treated with DES or BMS. METHODS: Consecutive elderly patients (>= 75 years old) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent<3mm) were recruited during 2004-2008. Procedural and long-term clinical outcomes were compared between patients treated with BMS and DES. Propensity score-adjusted logistic regression analysis was performed to account for potential selection bias. RESULTS: Among 293 patients (175 BMS, 118 DES), peri-procedural myocardial infarction (12 [7%] vs. 5 [4%]; P=0.35) and blood transfusions (3 [2%] vs. 0; P=0.08) were not significantly different between the BMS and DES groups. Clinical follow-up (96% of patients, median [interquartile range] follow-up 3.5 [2.4] years) showed significantly lower adjusted major adverse cardiac events (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.24 0.72; P=0.002) and target vessel revascularization (TVR) (HR 0.33, 95% CI 0.14 0.76; P=0.009) in the DES group. No significant differences were observed between the groups in terms of death, myocardial infarction, stent thrombosis or bleeding. CONCLUSIONS: In this retrospective, non-randomized analysis of the treatment of small vessel disease in elderly patients, DES were as safe and more effective than BMS with a significant reduction in TVR. PMID- 24231053 TI - Simple bedside clinical evaluation versus established scores in the estimation of operative risk in valve replacement for severe aortic stenosis. AB - BACKGROUND: The operative risk of cardiac surgery is ascertained preoperatively on the basis of scores validated in multinational studies. However, the value they add to a simple bedside clinical evaluation (CE) remains controversial. AIMS: To compare operative mortality (defined as death from all causes before the 31st postoperative day) predicted by CE with that predicted by additive and logistic EuroSCOREs, EuroSCORE II and Society of Thoracic Surgeons (STS), Ambler and age-creatinine-ejection fraction (ACEF) scores in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis. METHODS: Overall, 314 consecutive patients were included who underwent AVR between October 2009 and November 2011 (22% with coronary artery bypass graft); mean age 73.4 +/- 9.7 years (29% aged>80 years). Based on CE, patients were divided into four predefined groups of increasing estimated mortality risk: I <= 3.9%; II 4-6.9%; III 7-9.9%; IV >= 10%. The positive and negative predictive values of the six scores and CE were compared. RESULTS: The observed overall operative mortality was 5.7%. The distribution of the four predicted mortality groups by each score was highly variable. The positive predictive value, calculated for the 64 patients classified at highest risk by CE (groups III or IV) or each score, was 17.2% for EuroSCORE II, 14.1% for CE and STS scores, 10.9% for additive and logistic EuroSCOREs, 10.6% for ACEF and 10.2% for Ambler. The positive predictive value of each score in the low-risk groups (I and II) ranged from 2.8% to 4.4%. CONCLUSION: A simple bedside CE appears as reliable as the various established scores for predicting operative risk in patients undergoing surgical aortic valve replacement. The development and validation of more comprehensive risk stratification tools, including risk factors thus far neglected, seems warranted. PMID- 24231054 TI - Biomechanics of an integrated interbody device versus ACDF anterior locking plate in a single-level cervical spine fusion construct. AB - BACKGROUND CONTEXT: No profile, integrated interbody cages are designed to act as implants for cervical spine fusion, which obviates the need for additional internal fixation, combining the functionality of an interbody device and the stabilizing benefits of an anterior cervical plate. Biomechanical data are needed to determine if integrated interbody constructs afford similar stability to anterior plating in single-level cervical spine fusion constructs. PURPOSE: The purpose of this study was to biomechanically quantify the acute stabilizing effect conferred by a single low-profile device design with three integrated screws ("anchored cage"), and compare the range of motion reductions to those conferred by a standard four-hole rigid anterior plate following instrumentation at the C5-C6 level. We hypothesized that the anchored cage would confer comparable postoperative segmental rigidity to the cage and anterior plate construct. STUDY DESIGN: Biomechanical laboratory study of human cadaveric spines. METHODS: Seven human cadaveric cervical spines (C3-C7) were biomechanically evaluated using a nondestructive, nonconstraining, pure-moment loading protocol with loads applied in flexion, extension, lateral bending (right+left), and axial rotation (left+right) for the intact and instrumented conditions. Range of motion (ROM) at the instrumented level was the primary biomechanical outcome. Spines were loaded quasi-statically up to 1.5 N-m in 0.5 N m increments and ROM at the C5-C6 index level was recorded. Each specimen was tested in the following conditions: 1. Intact 2. Discectomy+anchored cage (STA) 3. Anchored cage (screws removed)+anterior locking plate (ALP) 4. Anchored cage only, without screws or plates (CO) RESULTS: ROM at the C5-C6 level was not statistically different in any motion plane between the STA and ALP treatment conditions (p>.407). STA demonstrated significant reductions in flexion/extension, lateral bending, and axial rotation ROM when compared with the CO condition (p<.022). CONCLUSIONS: In this in vitro biomechanical study, the anchored cage with three integrated screws afforded biomechanical stability comparable to that of the standard interbody cage+anterior plate cervical spine fusion approach. Due to its low profile design, this anchored cage device may avoid morbidities associated with standard anterior plating, such as dysphagia. PMID- 24231055 TI - Three-dimensional finite element analysis of occipitocervical fixation using an anterior occiput-to-axis locking plate system: a pilot study. AB - BACKGROUND CONTEXT: Although there are many techniques for occipitocervical fixation, there have been no reports regarding occipitocervical fixation via the use of an anterior anatomical locking plate system. PURPOSE: The biomechanics of this new system were analyzed by a three-dimensional finite element to provide a theoretical basis for clinical application. STUDY DESIGN: This was a modeling study. PATIENT SAMPLE: We studied a 27-year-old healthy male volunteer in whom cervical disease was excluded via X-ray examination. OUTCOME MEASURES: The states of stress and strain of these two internal fixation devices were analyzed. METHODS: A three-dimensional finite element model of normal occiput-C2 was established based on the anatomical data from a Chinese population. An unstable model of occipital-cervical region was established by subtracting several unit structures from the normal model. An anterior occiput-to-axis locking titanium plate system was then applied and an anterior occiput-to-axis screw fixation was performed on the unstable model. Limitation of motion was performed on the surface of the fixed model, and physiological loads were imposed on the surface of the skull base. RESULTS: Under various loads from different directions, the peak values of displacement of the anterior occiput-to-axis locking titanium plate system decreased 15.5%, 12.5%, 14.4%, and 23.7%, respectively, under the loads of flexion, extension, lateral bending, and axial rotation. Compared with the anterior occiput-to-axis screw fixation, the peak values of stress of the anterior occiput-to-axis locking titanium plate system also decreased 3.9%, 2.9%, 9.7%, and 7.2%, respectively, under the loads of flexion, extension, lateral bending, and axial rotation. CONCLUSION: The anterior occiput-to-axis locking titanium plate system proved superior to the anterior occiput-to-axis screw system both in the stress distribution and fixation stability based on finite element analysis. It provides a new clinical option for anterior occipitocervical fixation. PMID- 24231056 TI - Abnormal cingulum bundle development in autism: a probabilistic tractography study. AB - There is now considerable evidence that white matter abnormalities play a role in the neurobiology of autism. Little research has been directed, however, at understanding (a) typical white matter development in autism and how this relates to neurocognitive impairments observed in the disorder. In this study we used probabilistic tractography to identify the cingulum bundle in 21 adolescents and young adults with Autism Spectrum Disorder (ASD), and 21 age- and sex-matched healthy volunteers. We investigated group differences in the relationships between age and fractional anisotropy, a putative measure of white matter integrity, within the cingulum bundle. Moreover, in a preliminary investigation, we examined the relationship between cingulum fractional anisotropy and executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). The ASD participants demonstrated significantly lower fractional anisotropy within the cingulum bundle compared to the typically developing volunteers. There was a significant group-by-age interaction such that the ASD group did not show the typical age-associated increases in fractional anisotropy observed among healthy individuals. Moreover, lower fractional anisotropy within the cingulum bundle was associated with worse BRIEF behavioral regulation index scores in the ASD group. The current findings implicate a dysregulation in cingulum bundle white matter development occurring in late adolescence and early adulthood in ASD, and suggest that greater disturbances in this trajectory are associated with executive dysfunction in ASD. PMID- 24231057 TI - Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion. AB - Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p<0.01), while it reduced 300MUM acetylcholine (ACh) (p<0.01), 100MUM veratridine (Ver) (p<0.01) and 56mM K(+) (p<0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p<0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56mM K(+) induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p<0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p<0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti depressant-like effects. PMID- 24231058 TI - Stroke induced Sarcopenia: muscle wasting and disability after stroke. AB - Stroke is the second leading cause of death and the leading cause of disability in Western countries. More than 60% of patients remain disabled, 50% of patients suffer from hemiparesis and 30% remain unable to walk without assistance. The skeletal muscle is the main effector organ accountable for disability in stroke. This disability is primarily attributed to the brain lesion; however less attention is paid to structural, metabolic and functional alterations of muscle tissue after stroke. Hemiparetic stroke leads to various muscle abnormalities: A combination of denervation, disuse, inflammation, remodelling and spasticity accounts for a complex pattern of muscle tissue phenotype change and atrophy. The molecular mechanisms of muscle degradation after stroke are only incompletely understood. Reinnervation, fibre-type shift, disuse atrophy, and local inflammatory activation are only some of the key features yet to be explained. Only limited data is available today on clinical muscle changes after stroke that results from few studies in a mere 500 patients. Despite its importance for optimum post stroke recovery, stroke-related sarcopenia is not considered in current guidelines for stroke therapy or rehabilitation and measurement tools to address sarcopenia are infrequently used. This lack of robust evidence on muscle pathology after stroke and on treatment strategies needs to be addressed in an interdisciplinary integrated approach. This review provides an overview on current pathophysiologic insights and on clinical relevance of sarcopenia in stroke patients and on measurement tools to address the problem in the clinical setting. PMID- 24231059 TI - Prasugrel versus ticagrelor in acute coronary syndrome: a randomized comparison. PMID- 24231060 TI - Impact of reported sexual dysfunction on outcome in patients with chronic heart failure. PMID- 24231061 TI - Impact of aortic or mitral valve sclerosis and calcification on cardiovascular events and mortality: a meta-analysis. PMID- 24231062 TI - Effects of physical, technical, and tactical factors on final ladder position in semiprofessional rugby league. AB - PURPOSE: A limitation of most rugby league time-motion studies is that researchers have examined the demands of single teams, with no investigations of all teams in an entire competition. This study investigated the activity profiles and technical and tactical performances of successful and less-successful teams throughout an entire rugby league competition. METHODS: In total, 185 rugby league players representing 11 teams from a semiprofessional competition participated in this study. Global positioning system analysis was completed across the entire season. Video footage from individual matches was also coded via notational analysis for technical and tactical performance of teams. RESULTS: Trivial to small differences were found among Top 4, Middle 4, and Bottom 4 teams for absolute and relative total distances covered and distances covered at low speeds. Small, nonsignificant differences (P = .054, ES = 0.31) were found between groups for the distance covered sprinting, with Top 4 teams covering greater sprinting distances than Bottom 4 teams. Top 4 teams made more meters in attack and conceded fewer meters in defense than Bottom 4 teams. Bottom 4 teams had a greater percentage of slow play-the-balls in defense than Top 4 teams (74.8% +/- 7.3% vs 67.2% +/- 8.3%). Middle 4 teams showed the greatest reduction in high-speed running from the first to the second half (-20.4%), while Bottom 4 teams completed 14.3% more high-speed running in the second half than in the first half. CONCLUSION: These findings demonstrate that a combination of activity profiles and technical and tactical performance are associated with playing success in semiprofessional rugby league players. PMID- 24231063 TI - Obesity in kidney transplantation. AB - Kidney transplantation is the preferred modality of renal replacement therapy. Long-term patient and graft survival have only improved marginally over the recent decade, mainly because of the development of cardiovascular disease after transplantation. Obesity is a risk factor for cardiovascular disease and is common before and after transplantation. This article reviews the literature assessing the role of pre- and post-transplant obesity on patient and graft survival, discusses the underlying obesity-related mechanisms leading to inferior kidney transplant outcomes, and explores the role of nutritional intervention on improving long-term outcomes of transplantation. Although the role of pretransplant obesity remains uncertain, post-transplant obesity increases the risk of graft failure and mortality. Nutritional intervention is effective in achieving post-transplant weight loss, but the effect on long-term outcomes has not been established. Future research should focus on conducting nutritional intervention studies aiming to improve long-term outcomes of kidney transplantation. PMID- 24231064 TI - International Psychogeriatrics and the International Psychogeriatric Association: a successful marriage turns silver. PMID- 24231065 TI - Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: a systematic literature review. AB - OBJECTIVE: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. METHODS: We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010-2012 and EULAR 2010-2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. RESULTS: The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. CONCLUSION: As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition. PMID- 24231066 TI - Epigenetics and methylation in the rheumatic diseases. AB - OBJECTIVES: Rheumatic diseases encompass a wide range of conditions of poorly characterized etiopathology, many having both genetic and environmental susceptibility factors. Epigenetic studies are providing new insights into disease pathogenesis. Recent rheumatology literature related to DNA methylation studies-both epigenome-wide and candidate gene-are discussed, as well as methodological issues. METHOD: A PubMed search for articles published until April 2013 was conducted using the following keywords: ("methylation" OR "epigenetics") AND ("rheumatoid arthritis" OR "lupus" OR "autoimmune disease" OR "osteoporosis" OR "osteoarthritis" OR "musculoskeletal disorder") and EWAS. The reference lists of identified articles were searched for further articles. RESULTS: Several genome-wide methylation studies have been reported recently, mostly in autoimmune rheumatic diseases. Overall, these studies have identified methylation signatures in disease, clustering of subgroups as well as new and known epigenetic associations. Methodological issues, small sample sizes and reduced coverage of methylation assays render many results preliminary. CONCLUSIONS: There have been a number of epigenetic advances in rheumatic diseases recently. The new technologies and emerging field of epigenome-wide association will provide novel perspectives in disease etiology, diagnosis, classification, and therapy. PMID- 24231067 TI - Towards revealing the functions of all genes in plants. AB - The great recent progress made in identifying the molecular parts lists of organisms revealed the paucity of our understanding of what most of the parts do. In this review, we introduce computational and statistical approaches and omics data used for inferring gene function in plants, with an emphasis on network based inference. We also discuss caveats associated with network-based function predictions such as performance assessment, annotation propagation, the guilt-by association concept, and the meaning of hubs. Finally, we note the current limitations and possible future directions such as the need for gold standard data from several species, unified access to data and tools, quantitative comparison of data and tool quality, and high-throughput experimental validation platforms for systematic gene function elucidation in plants. PMID- 24231068 TI - Plastids with or without galactoglycerolipids. AB - In structural, functional, and evolutionary terms, galactoglycerolipids are signature lipids of chloroplasts. Their presence in nongreen plastids has been demonstrated in angiosperms and diatoms. Thus, galactoglycerolipids are considered as a landmark of green and nongreen plastids, deriving from either a primary or secondary endosymbiosis. The discovery of a plastid in Plasmodium falciparum, the causative agent of malaria, fueled the search for galactoglycerolipids as possible targets for treatments. However, recent data have provided evidence that the Plasmodium plastid does not contain any galactoglycerolipids. In this opinion article, we discuss questions raised by the loss of galactoglycerolipids during evolution: how have galactoglycerolipids been lost? How does the Plasmodium plastid maintain four membranes without these lipids? What are the main constituents instead of galactoglycerolipids? PMID- 24231069 TI - Antioxidant, antimicrobial and toxicological properties of Schinus molle L. essential oils. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. has been used in folk medicine as antibacterial, antiviral, topical antiseptic, antifungal, antioxidant, anti inflammatory, anti-tumoural as well as antispasmodic and analgesic; however, there are few studies of pharmacological and toxicological properties of Schinus molle essential oils. The aim of this study was to evaluate the antioxidant and antimicrobial activities of Schinus molle leaf and fruit essential oils, correlated with their chemical composition and evaluate their acute toxicity. MATERIALS AND METHODS: The chemical composition of Schinus molle leaf and fruit essential oils were evaluated by GC-FID and GC-MS. Antioxidant properties were determined using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical and beta carotene/linoleic acid methods. Antimicrobial properties were evaluated by the agar disc diffusion method and minimal inhibitory concentration assay. Toxicity in Artemia salina and acute toxicity with behavioural screening in mice were evaluated. RESULTS: The dominant compounds found in leaf and fruit essential oils (EOs) were monoterpene hydrocarbons, namely alpha-phellandrene, beta phellandrene, beta-myrcene, limonene and alpha-pinene. EOs showed low scavenging antioxidant activity by the DPPH free radical method and a higher activity by the beta-carotene/linoleic acid method. Antimicrobial activity of EOs was observed for Gram+, Gram- pathogenic bacteria and food spoilage fungi. EOs showed totoxicity for Artemia salina and lower toxicity in Swiss mice. CONCLUSIONS: The result showed that EOs of leaves and fruits of Schinus molle demonstrated antioxidant and antimicrobial properties, suggesting their potential use in food or pharmaceutical industries. PMID- 24231070 TI - Ethnomedicinal application of native remedies used against diabetes and related complications in Mauritius. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Notoriously, the tropical island of Mauritius has one of the highest prevalence of diabetes worldwide and the economic burden associated with it is alarming. The use of native remedies (NRs) is well anchored in the local culture and it continues to be the cornerstone of therapy for diabetic patients. However, there is currently a dearth of updated primary data on NRs used by Mauritians against diabetes and diabetes related complications (DRCs). This study was therefore designed to record, analyze and document orally transmitted ethnopharmacological knowledge from diabetic patients and traditional medicine practitioners (TMPs) in Mauritius concerning NRs commonly used against diabetes and DRCs which might open new avenues to initiate novel antidiabetic drugs discovery. MATERIALS AND METHODS: Data was collected following interviews from diabetic patients (n=328) and TMPs (n=20). Eleven quantitative indexes, namely informant consensus factor (FIC), fidelity level (FL), use value (UV), relative frequency of citation (RFC), relative importance (RI), cultural importance index (CII), index of agreement on remedies (IAR), cultural agreement index (CAI), quality use value (QUV), quality use agreement value (QUAV) and ethnobotanicity index (EI) were calculated. Statistical analysis such as Pearson correlation and Chi-squared test were performed to determine any association. RESULTS: A total of 111 plant species distributed over 56 families, 30 polyherbal formulations and 16 animal species were documented to be traditionally used against diabetes and DRCs. For the first time 8 endemic plants have been recorded to be used against diabetes and DRCs from Mauritius. The most encountered medicinal plant family was Asteraceae. According to the EI, 16.2% of the native plants in Mauritius were used against diabetes and DRCs. As far as we know, Vangueria madagascariensis, Apium graveolens, Petroselinum crispum and Rubus alceifolius with high RFC values are recorded against diabetes and DRCs for the first time. Sociodemographic characteristics (age, gender, income, religious belief, education and residence) were found to significantly (p<0.05) influence the use of NRs. The average FIC for all ailments for plant and animal products were 0.94 and 0.87 respectively. Bryophyllum pinnatum, a native plant to Mauritius scored a high FL value (100%) used against diabetic neuropathy, Allium sativum had the highest RI value (2.00) due to its versatility, Aloe vera had the highest RFC (0.61), the CII (0.640) and the highest CAI value (0.635), Psidium guajava had the highest QUAV (0.961) which indicates its high bioactivity and Allium cepa was reported as the most effective plant species (QUV=0.965). According to UV, the most important species was Morinda citrifolia (1.21). Panoply of animal products were reported whereby fish (39.7%) was recorded as the most utilised zootherapy and Salmo salar scored the highest FL (100%) for diabetes. Some animal species (n=14) not previously documented against diabetes and DRCs are reported in the present study. CONCLUSION: Our present investigation revealed that the use of NRs constitutes the common legacy of Mauritians and despite the penetration of allopathic medicine; NRs continue to play a crucial role in the primary health care system of Mauritius. To this effect, it is of uttermost importance to record this knowledge before it disappears. In addition, further experimental investigations are required to elucidate the pharmacological properties of the reported medicinal flora and fauna of Mauritius. PMID- 24231071 TI - 4-Methylthio-butanyl derivatives from the seeds of Raphanus sativus and their biological evaluation on anti-inflammatory and antitumor activities. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Raphanus sativus seeds (Brassicaceae) known as Raphani Semen have long been used as anti-cancer and/or anti-inflammatory agents in Korean traditional medicine. This study was designed to isolate the bioactive constituents from the seed extracts of Raphanus sativus and evaluate their anti inflammatory and antitumor activities. MATERIAL AND METHODS: Bioassay-guided fractionation and chemical investigation of a methanolic extract of the seeds of Raphanus sativus led to the isolation and identification of seven 4-methylthio butanyl derivatives. Structural elucidation of the isolated compounds was carried out using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques ((1)H, (13)C, COSY, HMQC and HMBC experiments) and mass spectrometry. RESULTS: The isolated compounds were characterized as in the following: three new 4 methylthio-butanyl derivatives, sinapoyl desulfoglucoraphenin (1), (E)-5 (methylsulfinyl)pent-4-enoxylimidic acid methyl ester (2), and (S)-5 ((methylsulfinyl)methyl)pyrrolidine-2-thione (3), together with four known compounds, 5-(methylsulfinyl)-4-pentenenitrile (4), 5-(methylsulfinyl) pentanenitrile (5), sulforaphene (6), and sulforaphane (7). Full NMR data assignments of the three known compounds 4-6 were also reported for the first time. We evaluated the anti-neuroinflammatory effect of 1-7 in lipopolysaccharide stimulated murine microglia BV2 cells. Compound 1 significantly inhibited nitrite oxide production with IC50 values of 45.36 MUM. Moreover, it also reduced the protein expression of inducible nitric oxide synthase. All isolates were also evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and all of them showed antiproliferative activity against the HCT-15 cell, with IC50 values of 8.49 23.97 MUM. CONCLUSIONS: 4-Methylthio-butanyl derivatives were one of the main compositions of Raphanus sativus seeds, and activities demonstrated by the isolated compounds support the ethnopharmacological use of Raphanus sativus seeds (Brassicaceae) as anti-cancer and/or anti-inflammatory agents. PMID- 24231072 TI - Matrine attenuates allergic airway inflammation and eosinophil infiltration by suppressing eotaxin and Th2 cytokine production in asthmatic mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Matrine has been isolated from Sophora flavescens, and found to show anti-inflammatory effects in macrophages and anti cachectic effects in hepatomas. The present study investigated whether matrine suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in mice, and decreased the inflammatory response of tracheal epithelial cells. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic asthma in mice. These asthmatic mice were given various doses of matrine by intraperitoneal injection. Additionally, activated human tracheal epithelial cells (BEAS-2B cells) were treated with matrine, and evaluated for levels of proinflammatory cytokines and chemokines. RESULTS: We found that matrine significantly decreased AHR, and suppressed goblet cell hyperplasia, eosinophil infiltration, and inflammatory response in the lung tissue of asthmatic mice. Matrine also reduced the levels of Th2 cytokines and chemokines in bronchoalveolar lavage fluid, and suppressed OVA-IgE production in serum. Furthermore, matrine treatment of activated BEAS-2B cells decreased production of proinflammatory cytokines and eotaxins, as well as suppressed ICAM-1 expression and thus adhesion of eosinophils to inflammatory BEAS-2B cells in vitro. CONCLUSIONS: Our findings suggest that matrine can improve allergic asthma in mice, and therefore has potential therapeutic potential in humans. PMID- 24231073 TI - Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL/6J mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps species which is well-known as 'winter worm summer grass' has long been used as tonics and stimulants to enhance energy, exhibiting a potential for energy metabolism. Clinical trials have suggested their beneficial effect on lipid metabolic disorders such as hyperlipidemia. MATERIALS AND METHODS: The effect of Cordyceps militaris on metabolic parameters was investigated using C58BL/6J mice induced by high-fat diet (HFD). The effect was first determined by assessing the body and organ weight. For further investigation, sections of epididymal adipose tissue were stained with hematoxylin and eosin and the size of epididymal adipocyte was measured by Image analysis system. Fat accumulation in frozen liver sections was assessed by the Oil Red O staining and the plasma biochemical parameters were also assessed. Active constituents were characterized using chromatographic and spectroscopic analysis. RESULTS: The administration of Cordyceps militaris extract (CE) at the dose of 100mg/kg and 300 mg/kg reduced body weight gain and food efficiency ratio induced by HFD. The amount of epididymal fat and size of adipocytes were also decreased by CE treatment. In addition, liver weight and fat deposition in liver were dramatically reduced in CE-treated group. The treatment of CE also showed beneficial effects on plasma parameters related to lipid profiles. Further study for the characterization of active constituents of Cordyceps resulted in the isolation of two new compounds such as cordyrroles A (1) and B (7) together with 12 known compounds including pyrrole alkaloids and nucleotide derivatives. Among the isolated compounds, cordyrrole A significantly inhibited adipocyte differentiation and pancreatic lipase activity, whereas cordyrrole B was more effective at inhibiting pancreatic lipase. Cordycepin, a characteristic compound of Cordyceps militaris, decreased the rate of adipocyte differentiation. CONCLUSION: Treatment of CE inhibited HFD-induced metabolic disorders, mainly by improvement in metabolic parameters. As active constituents, pyrrole alkaloids and nucleotide derivatives were characterized. These results suggested that Cordyceps militaris might be beneficial for the treatment of metabolic disorders obesity through the combined actions of diverse constituents. PMID- 24231074 TI - Assessment of the impact of a workplace intervention to reduce prolonged occupational sitting time. AB - We aim to provide a better picture of the outcomes associated with implementing a nonpurposeful, physical activity, e-health intervention in a professional workplace. There is a need for health professionals to evaluate physical-activity based workplace health interventions with a full range of measures. Using a social ecological model as a basis, we identify a range of subjective outcomes from 15 interviews of a cross section of participants. We document that not only did participants report a range of positive outcomes across multiple systems of influence, but they experienced some negative outcomes because of disruption to work flow and a changing of work habit. We conclude that using subjective evaluations provides a comprehensive picture of the factors that influence judgments of the efficacy of a workplace health intervention. PMID- 24231075 TI - Abbreviated injury scale: Not a reliable basis for summation of injury severity in trauma facilities [Ringdal et al., Int. J. Care Injured 44 (2013) 691-699]. PMID- 24231076 TI - The "obesity-mortality paradox" in severely traumatic patients in intensive care unit. PMID- 24231077 TI - Fabrication pentablock copolymer/silica hybrids as self-assembly coatings. AB - Novel organic/inorganic hybrid for coating material is prepared by the pentablock copolymer PDMS-b-(PMMA-b-PMPS)2 (PMMDMM) and SiO2 nanoparticles. PMMDMM is obtained via atom transfer radical polymerization (ATRP) by using polydimethylsiloxane (PDMS) as bifunctional macroinitiator. Poly 3 (trimethoxysilyl)propyl methacrylate (PMPS) is designed as the end block for facilitating the chemical bond of triethoxysilane (Si(OCH3)3) groups with SiO2 nanoparticles produced by tetraethyl orthosilicate (TEOS), and poly (methyl methacrylate) (PMMA) is designed as the middle block for improving the solubility and the film-forming ability of copolymer. The homogeneous dispersion of SiO2 nanoparticles in the pentablock copolymer matrix enables PMMDMM/SiO2 to self assemble into 210 nm SiO2 core/PMMDMM shell elliptic or spherical micelles in tetrahydrofuran (THF) solution. This self-assembled aggregate could provide the film surface with uniform distribution of SiO2 nanoparticles, obvious hydrophobicity (101-102 degrees water contact angles), lower surface free energy (22.3-21.8 nN/m) and lower viscoelasticity. SiO2 involved into the copolymer matrix could increase the nanostructures roughness. When TEOS is controlled as 20 wt.%, the hybrid performs higher glass transition temperature (Tg = 113 degrees C) and excellent thermostability (520 degrees C) than PMMDMM (Tg = 87 degrees C, 295 degrees C) due to the introduction of SiO2 nanoparticles. These excellent properties promise PMMDMM/SiO2 hybrid as the candidate for coating material. PMID- 24231078 TI - Slip flow of diverse liquids on robust superomniphobic surfaces. AB - Water slips exist over superhydrophobic solid surfaces, but the slip flow of diverse liquids on a single surface has not been deliberately studied to date. Here, we report the slip flow behavior of a variety of liquids with different surface tensions and viscosities on a robust omniphobic surface. This surface displayed a dramatic slippage effect and thus a high drag reduction efficiency of approximately 10-20% for all liquids, depending on both liquid viscosity and surface energy. The observed liquid slip was attributed to the surface dual micro/nanostructure and the low-surface-energy coating. PMID- 24231079 TI - Preparation and characterization of mesoporous silicas modified with chiral selectors as stationary phase for high-performance liquid chromatography. AB - New hybrid materials were prepared as novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). Pure mesoporous silica (SM) and ethylene-bridged periodic mesostructured organosilica (PMO) were functionalized, by a post-synthesis method, with derivates of erythromycin and vancomycin. N2 adsorption-desorption measurements, XRD, FT-IR, MAS NMR, SEM, TEM and elemental analysis were used to characterize the physico-chemical properties of these mesostructured materials, before and after the modification process. The synthesized particles had non-symmetrical 3-D wormhole-like mesostructure, spherical morphology, and a mean pore diameter between 53 and 59 A. CSPs prepared were tested for the separation of four chiral beta-blockers (atenolol, metoprolol, pindolol and propranolol) in normal phase (NP) and polar organic phase (PO) elution modes. Much stronger chiral interaction was observed in vancomycin-modified silicas. Results obtained in these preliminary studies will permit in future works to improve the synthesis route in order to design mesoporous materials with better performance as a chiral stationary phase for HPLC. PMID- 24231080 TI - From nanospheres to microribbons: Self-assembled Eosin Y doped PMMA nanoparticles as photonic crystals. AB - A modified emulsion synthesis of poly(methylmethacrylate) (PMMA) with the Eosin Y (EY), commercial chromophore, yields dye doped polymeric nanoparticles (PMMA@EY). A systematic investigation on the experimental parameters (monomer and initiator concentration, reaction time and MMA/EY molar ratio) has been explored to modulate physico-chemical properties of the dye doped polymeric colloids. Spherical shaped particles, doped with EY (0.5-3.0 wt%; loading efficiency eta = 11-15%), with controlled diameters in the range 240-510 nm, low dispersity and zeta-potential values in the range between -42 mV and -59 mV, have been synthesized and characterized by means of UV-Vis spectrometry, Dynamic Light Scattering (DLS), laser Doppler electrophoresis and Scanning Electron Microscopy (SEM). Microribbons based on PMMA@EY nanoparticles have been fabricated by room temperature self-assembly of aqueous colloidal suspension on highly wettable glass substrates. Surface chemical treatment assisted the formation of long (up to few centimeters) regular ribbons with rectangular section. Lateral size and height of the structures have been controlled by changing the suspension concentration and/or the deposition volume: the higher suspension concentration produces larger and thicker ribbons and the higher deposited volume produces thicker ribbons (up to 23 MUm with 198 MUL of a 3 wt% suspension). Moreover, a transition from a film-like to a ribbon-like growth has been observed with increasing nanoparticles concentration. Short range ordering and photonic crystal features have been maintained in the fluorescent ribbon microarchitecture, resulting in a self-assembled material with excellent potential for the development of mirror-less and random lasers. PMID- 24231081 TI - Evaporation induced self assembled microstructures of silica nanoparticles and Streptococcus lactis cells as sorbent for uranium (VI). AB - An assembled microstructure of silica nanoparticles and Streptococcus lactis (S. lactis) cells has been synthesized by evaporation induced self assembly, with the objective of its application in bioremediation. Different morphologies have been realized by tuning the physico-chemical conditions of the assembly process. The potential of these microstructures in removal of uranium (VI) has been evaluated. Morphology dependent uptake has been demonstrated and maximum uptake was seen for the spray dried doughnut shaped microstructure (SDSM). For a fixed morphology, the variation in uptake varies with solution pH, contact time, temperature and initial uranium (VI) concentration. The U (VI) removal was significantly rapid, with more than 85 +/- 2% of total uptake in 10 min. The maximum sorption capacity (qmax) of U (VI) at pH 5.0 and temperature 298 K was 169.5 mg/g using SDSM as sorbent. The kinetic data of adsorption of U (VI) are best described by a pseudo second-order kinetic model. Calculated thermodynamic parameters reveal an endothermic and a spontaneous adsorption process. The present work opens up the possibility of a means for the functionalization of silica microstructures through the incorporation of micro-organism and the potential for the use of these functionalized materials for bioremediation. PMID- 24231082 TI - Metal nanoparticles inside microgel/clay nanohybrids: Synthesis, characterization and catalytic efficiency in cross-coupling reactions. AB - HYPOTHESIS: Laponite nanoclay embedded inside soluble crosslinked copolymers (microgels) may act as cation exchanger allowing loading of the microgels with cationic metal precursors, which upon reduction yield tailored ternary colloidal nanocomposites comprising both nanoclay and metal nanoparticles. EXPERIMENTS: Microgel nanohybrids with variable Laponite nanoclay content were loaded with cationic precursors of different noble metals (Pd, Pt, Au); subsequent reduction by several methods yielded ternary nanocomposites which were extensively characterized. Nanocomposites based on Pd were also tested as catalysts in standard Suzuki and Sonogashira cross-coupling reactions. FINDINGS: The proposed method for the production of ternary nanocomposite microgels has been validated. The factors influencing the final metal nanoparticle size (nature of the reducing agent, clay content in the microgel) have been determined and rationalized. The resulting Pd-containing ternary nanocomposite microgels are viable catalysts of standard cross coupling reactions in water-rich medium. PMID- 24231083 TI - SDBS-assisted preparation of novel polyaniline planar-structure: morphology, mechanism and hydrophobicity. AB - Leaf-like hierarchical polyaniline (PANI) structure with interlaced nanofibers on the surface was prepared by chemical oxidation polymerization of aniline assisted by sodium dodecyl benzene sulfonate (SDBS). The chemical structure and the composition of the leaf-like PANI obtained were characterized by FTIR, UV-vis, XRD and XPS. In order to investigate the formation mechanism of such micro/nanostructures, some micro/nanostructures of PANI polymerized at different polymerization times were synthesized and observed for comparison. The results show that the PANI micro/nanostructures originate from PANI microleaves due to SDBS as soft template, which then covered with interlaced nanofibers on the surface. The leaf-like PANI micro/nanostructures exhibit good hydrophobic property with a water contact angle of 134.3 degrees resulted from the hydrophobic long dodecyl groups of SDBS dopant. PMID- 24231084 TI - An investigation of bubble coalescence and post-rupture oscillation in non-ionic surfactant solutions using high-speed cinematography. AB - Most processes involving bubbling in a liquid require small bubbles to maximise mass/energy transfer. A common method to prevent bubbles from coalescing is by the addition of surfactants. In order to get an insight into the coalescence process, capillary bubbles were observed using a high speed cinematography. Experiments were performed in solutions of 1-pentanol, 4-methyl-2-pentanol, tri(propylene glycol) methyl ether, and poly(propylene glycol) for which information such as the coalescence time and the deformation of the resultant bubble upon coalescence was extracted. It is shown in this study that the coalescence time increases with surfactant concentration until the appearance of a plateau. The increase in coalescence time with surfactant concentration could not be attributed only to surface elasticity. The oscillation of the resultant bubble was characterised by the damping of the oscillation. The results suggested that a minimum elasticity is required to achieve an increased damping and considerable diffusion has a detrimental effect on the dynamic response of the bubble, thereby reducing the damping. PMID- 24231085 TI - Hierarchical co-assembly avenue to uniform rhombododecahedral magnetic mesoporous graphitic composites. AB - Magnetic nanoparticles have been widely investigated due to their environmental and biomedical applications. However, the unavoidable problems associated with them are their intrinsic instability and the trend of the agglomeration. Mesoporous carbon is considered as an ideal matrix for the protection of magnetic nanoparticles owing to its high surface area, excellent chemical and thermal stability. The preparation of morphology defined composites of magnetic nanoparticles and mesoporous carbon is of great importance for their practical applications. In this work, magnetic mesoporous graphitic composites (MMGCs) with defined rhombododecahedral morphology are fabricated by the pyrolysis of the composites from the hierarchical co-assembly of amphiphilic triblock copolymer, resol oligomers and Fe3O4 nanoparticles. MMGCs exhibit narrow bimodal pore size distribution, high surface area and highly stable magnetic properties, which provide them excellent adsorption ability for the removal of organic contaminants in aqueous solution. PMID- 24231086 TI - The interaction of long chain sodium carboxylates and sodium dodecylsulfate with lead(II) ions in aqueous solutions. AB - The interaction of sodium octanoate, decanoate or dodecanoate with lead(II) has been studied in aqueous solutions using potentiometry, electrical conductivity, turbidity and ICP-OES measurements. These show an alkyl chain length dependence on the behavior. At the lead(II) concentration used (1.0 mM), relatively strong interactions are observed with the decanoate and dodecanaote, leading to formation of the lead carboxylates (soaps) as insoluble complexes. All techniques show 1:2 (metal:carboxylate) stoichiometry corresponding to charge neutralization. With sodium octanoate and lead(II), a rather weaker interaction is seen, and complexation is only observed at metal:carboxylate ratios > 0.5. However, in contrast to our previous work on octanoate and calcium(II) in aqueous solutions [1], precipitation does occur at higher concentrations. This difference between the behavior of the metal ions is probably due to the more covalent nature of the bonds of the carboxylate with Pb(2+) than with Ca(2+). Association constants of the complexes have been determined from potentiometric measurements and are consistent with data on solubility products. A comparison is made of the effect of surfactant head group on the interactions with lead(II) using two surfactants with the same chain length: dodecanoate and dodecylsulfate. Differences in their interactions with this metal ion in aqueous solutions are interpreted in terms of greater covalency of the bond between the metal and the carboxylate than with the sulfate group. PMID- 24231087 TI - Effect of architecture on the activity of glucose oxidase/horseradish peroxidase/carbon nanoparticle conjugates. AB - We investigate the activity of glucose oxidase (GOx) together with horseradish peroxidase (HRP) on carbon nanoparticles (CNPs). Because GOx activity relies on HRP, we probe how the arrangement of the enzymes on the CNPs affects enzymatic behavior. Colorimetric assays to probe activity found that the coupling strategy affects activity of the bienzyme-nanoparticle complex. GOx is more prone than HRP to denaturation on the CNP surface, where its activity is compromised, while HRP activity is enhanced when interfaced to the CNP. Thus, arrangements where HRP is directly on the surface of the CNP and GOx is not are more favorable for overall activity. Coverage also influenced activity of the bienzyme complex, but performing the conjugation in the presence of glucose did not improve GOx activity. These results show that the architecture of the assembly is an important factor in optimization of nanoparticle-protein interfaces. PMID- 24231088 TI - Interaction of normal and reverse pluronics (L44 and 10R5) and their mixtures with anionic surfactant sodium N-dodecanoylsarcosinate. AB - Interaction of monomeric normal L44 [(PEO)10(PPO)23(PEO)10]) and reverse 10R5 [(PPO)8(PEO)22(PPO)8] pluronics designated as L and R, respectively, and their mixtures with the anionic surfactant sodium N-dodecanoylsarcosinate (SDDS) in aqueous medium has been studied by tensiometry, conductometry, calorimetry and dynamic light scattering methods. The critical aggregation concentration (CAC), concentration of maximum binding (CS), and the extended critical micelle concentration (CMCe) of SDDS resulted from the interaction have been presented. L has shown the formation of CAC, CS and CMCe, whereas R has shown the absence of CAC but the presence of both CS and CMCe. Micellization of SDDS is an endothermic process whereas the formation of CAC and CMCe is exothermic events, the formation of CS is endothermic. The hydrodynamic diameter (Dh) and zeta potential of L and R, and their SDDS interacted species have been determined. Dh decreased with increasing SDDS concentration for L whereas it was invariant for R. Mixed L and R in varied proportions have been also examined in the solution state to probe into their mutual interaction, and interaction with SDDS. The formation of CAC of their mixtures was absent; CMCe formation was exothermic while that of CS was endothermic like their individuals. PMID- 24231089 TI - An electrochemical biosensor with nanointerface for lactate detection based on lactate dehydrogenase immobilized on zinc oxide nanorods. AB - Hepatic immaturity is observed particularly in children whose age is under three, when the lactate concentration is greater than the normal level in blood. An electrochemical lactate biosensor was developed by immobilizing lactate dehydrogenase (LDH) on to ZnO nanorods at pH 7.4 via chitosan. Growth of polycrystalline ZnO nanorods towards (101) plane was confirmed using XRD. The FE SEM study revealed the formation of ZnO nanorods with an aspect ratio of 3.24. Immobilization of LDH on ZnO nanorods was confirmed using FTIR spectra and surface coverage. Electrochemical studies were carried out through cyclic voltammetry and amperometry using three electrode system with Au/NanoZnO/LDH as working electrode, Ag/AgCl in 0.1 M KCl as reference electrode and Pt wire as counter electrode. The sensitivity of the biosensor was found to be 1.832 MUA MUmol(-1) L exhibiting linearity 0.2-0.8 MUmol L(-1) with the detection and quantification limits of 4.73 and 15.75 nmol L(-1) respectively. The response time of Au/NanoZnO/LDH bioelectrode was found to be <1 s. Prediction band for net current was framed to enhance specificity. Michaelis-Menten constant (KM(app)) and maximum rate (Imax) values for immobilized LDH were found to be 0.38 MUmol L( 1) and 2.798 MUA respectively. Repeatability and reproducibility of LDH biosensor were also reported. PMID- 24231090 TI - Human serum albumin and other proteins as templating agents for the synthesis of nanosized dopamine-eumelanin. AB - Eumelanin like materials are known to be heterogeneous and highly insoluble materials and hence it was difficult to use them for applications even if they display fascinating properties as photoprotection and photoconductivity. Owing to the known reactivity of quinones available on the surface of dopamine-eumelanin particles with nucleophiles, we propose and demonstrate that proteins (among them human serum albumin, hen egg white lysozyme and alpha-lactalbumine from bovine milk) are able to control the size of dopamine-eumelanin aggregates formed in dopamine solutions upon oxidation. The particles obtained in the presence of human serum albumin can be as small as 30 nm in diameter and the viability of human gingival fibroblasts is not significantly affected (with respect to pure dopamine-eumelanin) in the presence of such particles provided they are diluted enough. PMID- 24231091 TI - Effect of ethylene glycol on the special counterion binding and microstructures of sodium dioctylsulfosuccinate micelles. AB - Sodium dioctylsulfosuccinate (AOT) micelle has a special counterion binding behavior (SCB), which refers to the abrupt twofold increase in the counterion binding constant (beta) at a critical concentration (c*) of added NaCl (in water c* ~ 0.015 mol kg(-1)). In this paper, the SCB of AOT has been studied in a mixture of water and ethylene glycol (EG) by applying surface tension, fluorescence, and small angle neutron scattering (SANS) methods. The SCB exists in water + 10% (w/w) EG as well, but disappears when the EG% is >=20. It has been found out that the SCB of AOT occurs in media having cohesive energy density values in the range of 2.3-2.75 J m(-3). SANS data indicate co-existence of vesicles and cylindrical micelles of AOT in water + 10% EG when the added NaCl concentration is greater than c* thereby revealing that change in the morphology of aggregated species is the probable cause for the SCB of AOT. From this study it has become clear that the Corrin-Harkins (CH) equation, commonly used for determining beta, can be applied only above a limiting concentration (ce(#)) of added electrolyte. In aqueous organic or pure organic polar solvents below ce(#) sharp deviation from the CH equation occurs with reversal of slope rendering this equation inapplicable for the determination of beta. PMID- 24231092 TI - Peginterferon alfa-2a plus ribavirin for hemophilic patients with chronic hepatitis C virus infection in Taiwan. AB - BACKGROUND/PURPOSE: Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with hemophilia. However, the efficacy and safety of pegylated interferon (PEG-IFN) plus ribavirin (RBV) for hemophilic patients with chronic HCV infection in Taiwan are still unknown. The aim of this study is to report the efficacy and safety of PEG-IFN plus RBV in a single center in Taiwan. METHODS: In an open-label single-treatment one-arm cohort study, 12 hemophilic patients with elevated alanine aminotransferase level more than two times the upper limit of normal for more than 3 months received 180 MUg/week of PEG-IFN-alpha-2a plus RBV 1000-1200 mg/day at a cut-off value of 75 kg. The duration of treatment was 48 weeks for patients with HCV Genotype 1/4 infection and 24 weeks for patients with HCV Genotype 2/3 infection. Efficacy of therapy was expressed as sustained virological response (SVR). RESULTS: Eight patients achieved SVR (66.7%). The SVR rates were 57%, 100%, 100%, and 0% for patients with HCV Genotypes 1, 2, 3, and 4 infection, respectively. Adverse events (AEs) developed in 10 patients (83.3%). Severe thrombocytopenia developed in one patient. However, the patient did not suffer from severe bleeding. CONCLUSION: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-alpha-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well conducted studies are still needed to verify the treatment efficacy and safety. PMID- 24231093 TI - Lessons we learn from hematopathology consultation in Taiwan. AB - The appropriate management of hematology patients depends first on correct diagnoses. Expert review is important in reaching accurate diagnoses. To improve diagnostic accuracy, the Taiwan Society of Pathology and the Taiwan Division of the International Academy of Pathology has been conducting an expert consultation program for general pathologists since 2001. As per this program, we have received a total of 395 cases (406 samples) for review. We found that meaningful diagnostic discrepancies occurred frequently in hematopathology reviews. Ambiguous or nondiagnostic original reports were the major causative factor for the major discrepancy cases, which demonstrates that diagnostic uncertainty is a big problem for referring pathologists. However, the World Health Organization lymphoma classification may be poorly reproducible in countries where extensive use of an ancillary technique is not used by general pathologists. This review is intended to report the misdiagnoses most commonly seen in the hematopathology practice in Taiwan. Awareness of the easily misinterpreted entities helps to achieve the right diagnosis and improve patient care. PMID- 24231094 TI - Are statins really wonder drugs? AB - Statins [3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase], are wonder drugs that have reshaped the treatment of hypercholesterolemia and associated cardiovascular diseases. However, evidence from various studies indicates existence of many statin-induced side effects such as myopathies, rhabdomyolysis, hepatotoxicity, peripheral neuropathy, impaired myocardial contractility, diabetes, autoimmune diseases, and erectile dysfunction (ED). Physician awareness of these side effects is reported to be very low even for the adverse effects (AEs) most widely reported by patients. This can lead to incorrect treatment decisions, compromised patient care, and an increase in patient morbidity. Therefore, the aim of this article is to highlight the AEs of statin therapy as well as rational management of these complications to further improve safety of these excellent drugs. PMID- 24231095 TI - In vivo confocal microscopy of bulbar conjunctiva in patients with Graves' ophthalmopathy. AB - BACKGROUND/PURPOSE: To investigate the bulbar conjunctival changes in patients with Graves' ophthalmopathy (GO) using in vivo confocal microscopy. METHODS: A total of 15 GO patients and 15 control patients were recruited. Images of the superior site and temporal bulbar conjunctivas were taken by the Heidelberg Retina Tomograph/Rostock Corneal Module. The conjunctival thickness and cell density of superior epithelium, basal epithelium, Langerhans cells, and goblet cells were analyzed. Conjunctival impression cytology was performed to assess the grading of squamous metaplasia of the conjunctival epithelium. RESULTS: The superficial epithelial cell density in the superior bulbar conjunctiva of the GO group was 856.93 +/- 461.68 cells/mm(2), which was significantly lower than that in the control group (1581.13 +/- 556.34 cells/mm(2); p = 0.002). However, the difference in superficial epithelial cell density in the temporal bulbar conjunctiva between the two groups was not statistically significant. No significant differences in conjunctival thickness and the basal epithelial cell density were noted between the two groups. Increased Langerhans cell density and reduced goblet cell density were noted in the GO group. Impression cytology of the conjunctival epithelium revealed significantly higher degree of squamous metaplasia in the GO group. The superficial epithelial cell density in the upper bulbar conjunctiva showed negative correlation with marginal reflex distance in the GO group. CONCLUSION: GO patients suffered from more severe bulbar conjunctival damage and inflammation with the superior site than the temporal site. In vivo confocal microscopy can be a rapid and noninvasive tool for the quantitative evaluation of ocular surface changes in patients with GO. PMID- 24231096 TI - The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells. AB - Intestinally produced triglyceride-rich lipoproteins (TRL) play an important role in the progression of atherosclerosis. In this study, we investigated the relevance of monounsaturated fatty acid (MUFA) and saturated fatty acid (SFA) in postprandial TRL in affecting the transcriptional activity of the apolipoprotein B48 receptor (ApoB48R) and its functionality in human monocyte/macrophage cells. Healthy male volunteers were administered four standardized high-fat meals containing butter, high-palmitic sunflower oil, olive oil (ROO) or a mixture of vegetable and fish oils (50 g/m(2) body surface area) to obtain a panel of postprandial TRL with gradual MUFA oleic acid-to-SFA palmitic acid ratios. The increase in this ratio was linearly associated with a decrease of ApoB48R up regulation and lipid accumulation in THP-1 and primary monocytes. ApoB48R mRNA levels and intracellular triglycerides were also lower in the monocytes from volunteers after the ingestion of the ROO meal when compared to the ingestion of the butter meal. In THP-1 macrophages, the increase in the MUFA oleic acid-to-SFA palmitic acid ratio in the postprandial TRL was linearly correlated with an increase in ApoB48R down-regulation and a decrease in lipid accumulation. We also revealed that the nuclear receptor transcription factors PPARalpha, PPARbeta/delta, and PPARgamma and the PPAR-RXR transcriptional complex were involved in sensing the proportion of MUFA oleic acid and SFA palmitic acid, and these were also involved in adjusting the transcriptional activity of ApoB48R. The results of this study support the notion that MUFA-rich dietary fats may prevent excessive lipid accumulation in monocyte/macrophage cells by targeting the postprandial TRL/ApoB48R axis. PMID- 24231097 TI - Pomegranate reverses methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF-kappaB pathways. AB - The clinical efficacy of the widely used chemotherapeutic drug methotrexate (MTX) is limited due to its associated hepatotoxicity. Pomegranate polyphenols are of huge health benefits and known to possess remarkable antioxidant properties capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. In this study, we explored the protective role of pomegranate fruit extract (PFE) in ameliorating MTX-induced hepatic damage. Male Swiss albino mice exposed to MTX (20 mg/kg body weight) exhibited distinct markers of toxicity such as increased activities of enzymes alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase and also increased oxidative stress in liver evidenced by increased ROS generation and lipid peroxidation. Decrease in reduced glutathione levels, superoxide dismutase, catalase, hepatic heme oxygenase 1 and NQO-1 activities were also observed. Tracing the signal transduction pathways, it was seen that MTX exposure significantly increased nuclear translocation of NF-kappaB coupled with increase in phosphorylated Ikappa-B and down-regulation of NF-kappaB-dependent antiapoptotic protein Bcl-2. Treatment with MTX increased the expression of the apoptotic enhancer Rho/Cdc42 as well as the phosphorylation of SAPK/JNK. A shift in the Bax/Bcl-2 ratio towards apoptosis and increase in the caspase 3 level was also evident. Administration of PFE for 7 consecutive days before and after MTX challenge suppressed MTX-induced cell death, mitigated the injurious effects of MTX and offered protection against apoptosis. PFE was shown to reduce ROS generation in hepatocytes by activating the Nrf2-ARE pathway and inhibiting NF kappaB as a consequence of which the antioxidant defense mechanism in the liver was up-regulated, thereby conferring protection against MTX-induced hepatotoxicity and apoptosis. PMID- 24231099 TI - Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. AB - Pyrroloquinoline quinone (PQQ) influences energy-related metabolism and neurologic functions in animals. The mechanism of action involves interactions with cell signaling pathways and mitochondrial function. However, little is known about the response to PQQ in humans. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). Multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential [based on total peroxyl radical-trapping potential and thiobarbituric acid reactive product (TBAR) assays] were made throughout the period of 48 h. In study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation [plasma C-reactive protein, interleukin (IL)-6 levels], standard clinical indices (e.g., cholesterol, glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, etc.) and (1)H-nuclear magnetic resonance estimates of urinary metabolites related in part to oxidative metabolism. The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans. PMID- 24231098 TI - Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer. AB - In the US alone, around 60,000 lives/year are lost due to colon cancer. Diet and environment have been implicated in the development of sporadic colon tumors. The objective of this study was to determine how dietary fat potentiates the development of colon tumors through altered B(a)P biotransformation, using the Adenomatous polyposis coli with Multiple intestinal neoplasia mouse model. Benzo(a)pyrene was administered to mice through tricaprylin, and unsaturated (USF; peanut oil) and saturated (SF; coconut oil) fats at doses of 50 and 100 MUg/kg via oral gavage over a 60-day period. Blood, colon, and liver were collected at the end of exposure period. The expression of B(a)P biotransformation enzymes [cytochrome P450 (CYP)1A1, CYP1B1 and glutathione-S transferase] in liver and colon were assayed at the level of protein, mRNA and activities. Plasma and tissue samples were analyzed by reverse phase high performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the (32)P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose dependent manner, with 100 MUg/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater concentration of B(a)P metabolites, compared to the 50 MUg/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen. PMID- 24231100 TI - DSS-induced acute colitis in C57BL/6 mice is mitigated by sulforaphane pre treatment. AB - The Brassica-derived isothiocyanate sulforaphane (SFN) is known to induce factor erythroid 2-related factor 2 (Nrf2), a transcription factor centrally involved in chemoprevention. Furthermore, SFN exhibits anti-inflammatory properties in vitro and in vivo. However, little is known regarding the anti-inflammatory properties of SFN in severe inflammatory phenotypes. In the present study, we tested if pre treatment with SFN protects mice from dextran sodium sulphate (DSS)-induced colitis. C57BL/6 mice received either phosphate-buffered saline (control) or 25 mg/kg body weight (BW) SFN per os for 7 days. Subsequently, acute colitis was induced by administering 4% DSS via drinking water for 5 days and BWs, stool consistency and faecal blood loss were recorded. Following endoscopic colonoscopy, mice were sacrificed, the organs excised and spleen weights and colon lengths measured. For histopathological analysis, distal colon samples were fixed in 4% para-formaldehyde, sectioned and stained with hematoxylin/eosin. Inflammatory biomarkers were also measured in distal colon. Treatment with SFN prior to colitis induction significantly minimised both BW loss and the disease activity index compared to control mice. Furthermore, colon lengths in SFN pre treated mice were significantly longer than in control mice. Both macroscopic and microscopic analysis of the colon revealed attenuated inflammation in SFN pre treated animals. mRNA analysis of distal colon samples confirmed reduced expression of inflammatory markers and increased expression of Nrf2-dependent genes in SFN pre-treated mice. Our results indicate that pre-treating mice with SFN confers protection from DSS-induced colitis. These protective effects were corroborated macroscopically, microscopically and at the molecular level. PMID- 24231101 TI - Serum metabolites of proanthocyanidin-administered rats decrease lipid synthesis in HepG2 cells. AB - The regular consumption of flavonoids has been associated with reduced mortality and a decreased risk of cardiovascular diseases. The proanthocyanidins found in plasma are very different from the original flavonoids in food sources. The use of physiologically appropriate conjugates of proanthocyanidins is essential for the in vitro analysis of flavonoid bioactivity. In this study, the effect of different proanthocyanidin-rich extracts, which were obtained from cocoa (CCX), French maritime pine bark (Pycnogenol extract, PYC) and grape seed (GSPE), on lipid homeostasis was evaluated. Hepatic human cells (HepG2 cells) were treated with 25 mg/L of CCX, PYC or GSPE. We also performed in vitro experiments to assess the effect on lipid synthesis that is induced by the bioactive GSPE proanthocyanidins using the physiological metabolites that are present in the serum of GSPE-administered rats. For this, Wistar rats were administered 1 g/kg of GSPE, and serum was collected after 2 h. The semipurified serum of GSPE administered rats was fully characterized by liquid chromatography tandem triple quadrupole mass spectrometry (LC-QqQ/MS(2)). The lipids studied in the analyses were free cholesterol (FC), cholesterol ester (CE) and triglycerides (TG). All three proanthocyanidin-rich extracts induced a remarkable decrease in the de novo lipid synthesis in HepG2 cells. Moreover, GSPE rat serum metabolites reduced the total percentage of CE, FC and particularly TG; this reduction was significantly higher than that observed in the cells directly treated with GSPE. In conclusion, the bioactivity of the physiological metabolites that are present in the serum of rats after their ingestion of a proanthocyanidin-rich extract was demonstrated in Hep G2 cells. PMID- 24231102 TI - Dietary oleanolic acid mediates circadian clock gene expression in liver independently of diet and animal model but requires apolipoprotein A1. AB - Oleanolic acid is a triterpene widely distributed throughout the plant kingdom and present in virgin olive oil at a concentration of 57 mg/kg. To test the hypotheses that its long-term administration could modify hepatic gene expression in several animal models and that this could be influenced by the presence of APOA1-containing high-density lipoproteins (HDLs), diets including 0.01% oleanolic acid were provided to Apoe- and Apoa1-deficient mice and F344 rats. Hepatic transcriptome was analyzed in Apoe-deficient mice fed long-term semipurified Western diets differing in the oleanolic acid content. Gene expression changes, confirmed by reverse transcriptase quantitative polymerase chain reaction, were sought for their implication in hepatic steatosis. To establish the effect of oleanolic acid independently of diet and animal model, male rats were fed chow diet with or without oleanolic acid, and to test the influence of HDL, Apoa1-deficient mice consuming the latter diet were used. In Apoe-deficient mice, oleanolic acid intake increased hepatic area occupied by lipid droplets with no change in oxidative stress. Bmal1 and the other core component of the circadian clock, Clock, together with Elovl3, Tubb2a and Cldn1 expressions, were significantly increased, while Amy2a5, Usp2, Per3 and Thrsp were significantly decreased in mice receiving the compound. Bmal1 and Cldn1 expressions were positively associated with lipid droplets. Increased Clock and Bmal1 expressions were also observed in rats, but not in Apoa1-deficient mice. The core liver clock components Clock-Bmal1 are a target of oleanolic acid in two animal models independently of the diets provided, and this compound requires APOA1-HDL for its hepatic action. PMID- 24231103 TI - Intake of butter naturally enriched with cis9,trans11 conjugated linoleic acid reduces systemic inflammatory mediators in healthy young adults. AB - A conjugated linoleic acid (CLA) depletion-repletion study was carried out to investigate the effects of dietary c9,t11 CLA on C-reactive protein, transcription factor NFkappaB, metalloproteinases 2 and 9, inflammatory mediators (adiponectin, TNFalpha, IL-2, IL-4, IL-8, IL-10), body composition, and erythrocyte membrane composition in healthy normal-weight human adults. CLA depletion was achieved through an 8-week period of restricted dairy fat intake (depletion phase; CLA intake was 5.2+/-5.8 mg/day), followed by an 8-week period in which individuals consumed 20 g/day of butter naturally enriched with c9,t11 CLA (repletion phase; CLA intake of 1020+/-167 mg/day). The participants were 29 healthy adult volunteers (19 women and 10 men, aged 22 to 36 years), with body mass index between 18.0 and 29.9 kg m(-2). Blood samples were collected at baseline and at the end of both depletion and repletion phases. The content of CLA in erythrocytes decreased during CLA-depletion and increased during CLA repletion. Intake of CLA-enriched butter increased the serum levels of anti inflammatory IL-10 but reduced transcription factor NFkappaB in blood and serum levels of TNFalpha, IL-2, IL-8 and inactive metalloproteinase-9. Moreover, reduced activity of metalloproteinases 2 and 9 in serum was observed during the CLA-repletion period. In contrast, intake of CLA-enriched butter had no effects on body composition (DXA analysis) as well as on serum levels of adiponectin, C reactive protein, and IL-4. Taken together, our results indicate that the intake of a c9,t11 CLA-enriched butter by normal-weight subjects induces beneficial changes in immune modulators associated with sub-clinical inflammation in overweight individuals. PMID- 24231104 TI - Role of the inhibition of oxidative stress and inflammatory mediators in the neuroprotective effects of hydroxytyrosol in rat brain slices subjected to hypoxia reoxygenation. AB - The aim of this study was to analyze the mechanism of the neuroprotective effect of hydroxytyrosol (HT) in an experimental model of hypoxia-reoxygenation in rat brain slices. After reoxygenation the increase in lactate dehydrogenase efflux was inhibited by HT in a concentration-dependent manner and dose-dependent inhibition after oral administration to rats for 7 days (1, 5 and 10 mg/kg per day). Maximum inhibition was 57.4% in vitro and 38.7% ex vivo. Hydroxytyrosol reduced oxidative stress parameters: it inhibited lipid peroxidation and increased enzymatic activities related with the glutathione system both in vitro and after oral administration to rats. The increase in prostaglandin E2 and interleukin 1beta after reoxygenation were inhibited after incubation of brain slices with HT and after oral administration. The accumulation of nitric oxide in brain slices was reduced in a concentration-dependent manner. In conclusion, HT exerts a neuroprotective effect in a model of hypoxia-reoxygenation in rat brain slices, both in vitro and after 7 days of oral administration to rats. HT exerts an antioxidant activity and lowered some inflammatory markers in this model. PMID- 24231105 TI - Liver X receptor up-regulates alpha-tocopherol transfer protein expression and alpha-tocopherol status. AB - Fat-soluble vitamin E (alpha-tocopherol) has antioxidant activity. alpha Tocopherol transfer protein (alpha-TTP), a hepatic cytosolic protein, selectively binds alpha-tocopherol and has an important role regulating circulatory alpha tocopherol levels. However, only a few studies have shown the transcriptional regulation of the alpha-TTP gene. Here, we demonstrate that liver X receptor (LXR) regulates alpha-TTP expression through direct interaction with the alpha TTP gene promoter, and it modulates circulating alpha-tocopherol levels. LXR belongs to the nuclear receptor superfamily, acts as a ligand-dependent transcription factor for oxysterols and plays an important role in cholesterol metabolism and lipogenesis. We identified an LXR response element (LXRE; DR4, a direct repeat with four-nucleotides spacing) of the human alpha-TTP gene promoter by using luciferase and electrophoretic mobility shift assays. Mutations in this element abolished activation of this promoter. Moreover, treatment of vitamin E deficient rats with T0901317, a synthetic LXR ligand, increased alpha-TTP expression in the liver and cerebrum and increased the plasma alpha-tocopherol levels. These results indicate that the LXR signaling pathway modulates alpha-TTP gene expression and plasma alpha-tocopherol levels. Our observations imply that the LXR signaling pathway might be a useful target for antioxidant properties by controlling the vitamin E status. PMID- 24231107 TI - Linking the transcriptome and proteome to characterize the venom of the eastern diamondback rattlesnake (Crotalus adamanteus). AB - Understanding the molecular basis of the phenotype is key to understanding adaptation, and the relationship between genes and specific traits is represented by the genotype-phenotype map. The specialization of the venom-gland towards toxin production enables the use of transcriptomics to identify a large number of loci that contribute to a complex phenotype (i.e., venom), while proteomic techniques allow verification of the secretion of the proteins produced by these loci, creating a genotype-phenotype map. We used the extensive database of mRNA transcripts generated by the venom-gland transcriptome of Crotalus adamanteus along with proteomic techniques to complete the genotype-phenotype map for the C. adamanteus venom system. Nanospray LC/MS(E) analysis of a whole venom sample identified evidence for 52 of the 78 unique putative toxin transcript clusters, including 44 of the 50 most highly expressed transcripts. Tandem mass spectrometry and SDS-PAGE of reversed-phase high-performance liquid chromatography fractions identified 40 toxins which clustered into 20 groups and represented 10 toxin families, creating a genotype-phenotype map. By using the transcriptome to understand the proteome we were able to achieve locus-specific resolution and provide a detailed characterization of the C. adamanteus venom system. BIOLOGICAL SIGNIFICANCE: Identifying the mechanisms by which genetic variation presents itself to the sieve of selection at the phenotypic level is key to understanding the molecular basis of adaptation, and the first step in understanding this relationship is to identify the genetic basis of the phenotype through the construction of a genotype-phenotype map. We used the high-throughput venom-gland transcriptomic characterization of the eastern diamondback rattlesnake (C. adamanteus) and proteomic techniques to complete and confirm the genotype-phenotype map, providing a detailed characterization of the C. adamanteus venom system. PMID- 24231106 TI - Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes. AB - Resveratrol (RSV) is a plant polyphenol that exhibits several favorable effects on glucose homeostasis in adipocytes. Recent studies from our laboratory demonstrated that coplanar polychlorinated biphenyls (PCBs) that are ligands of the aryl hydrocarbon receptor impair glucose homeostasis in mice. PCB-induced impairment of glucose homeostasis was associated with augmented expression of inflammatory cytokines in adipose tissue, a site for accumulation of lipophilic PCBs. This study determined if RSV protects against PCB-77 induced impairment of glucose disposal in vitro and in vivo and if these beneficial effects are associated with enhanced nuclear factor erythoid 2-related factor 2 (Nrf2) signaling in adipose tissue. PCB-77 increased oxidative stress and abolished insulin stimulated 2-deoxy-d-glucose uptake in 3 T3-L1 adipocytes. These effects were restored by RSV, which resulted in a concentration-dependent increase in NAD(P)H:quinone oxidoreductase 1 (NQO1), the downstream target of Nrf2 signaling. We quantified glucose and insulin tolerance and components of Nrf2 and insulin signaling cascades in adipose tissue of male C57BL/6 mice administered vehicle or PCB-77 (50 mg/kg) and fed a diet with or without resVida (0.1%, or 160 mg/kg per day). PCB-77 impaired glucose and insulin tolerance, and these effects were reversed by RSV. PCB-77 induced reductions in insulin signaling in adipose tissue were also abolished by RSV, which increased NQO1 expression. These results demonstrate that coplanar PCB-induced impairment of glucose homeostasis in mice can be prevented by RSV, potentially through stimulation of Nrf2 signaling and enhanced insulin stimulated glucose disposal in adipose tissue. PMID- 24231108 TI - Isotope dilution mass spectrometry for absolute quantification in proteomics: concepts and strategies. AB - Isotope dilution mass spectrometry is a reference technique for quantitative analysis, given that it combines the sensitivity and selectivity of MS instruments with the precision and accuracy associated with the use of internal standards. Isotope-labeled proteins are the optimal internal standards for quantitative proteomics as they closely mimic the behavior of their natural counterparts during the analytical process. A major complication of isotope dilution mass spectrometry proteomics is the technical difficulty of obtaining these internal standards, especially in studies where a high number of proteins have to be quantified simultaneously. In this paper, we review some of the characteristics of the isotope dilution mass spectrometry approach, its benefits in terms of reliability and quality control in targeted proteomic analysis and the different strategies developed for its application in proteomics. PMID- 24231109 TI - Proteomic and functional profiling of the venom of Bothrops ayerbei from Cauca, Colombia, reveals striking interspecific variation with Bothrops asper venom. AB - Bothrops ayerbei, a pitviper inhabiting the Patia River's basin (Valle Alto del Rio Patia) in the Southwestern Department of Cauca, Colombia, was considered as a variant form of Bothrops asper prior to being proposed as a new species in 2010, on the basis of subtle morphological differences. This study reports the proteomic and functional profiling of B. ayerbei venom. Its most striking feature is an almost complete absence (0.7%) of phospholipases A2 (PLA2), which is in contrast to the high proportion of these enzymes (25.3%) in the venom of B. asper from Cauca, as well as in other species of Bothrops. The predominant proteins in B. ayerbei venom are metalloproteinases (53.7%), in agreement with its higher hemorrhagic and lethal activities compared to B. asper venom. Moreover, the negligible content of PLA2s in B. ayerbei venom correlates with its weaker myotoxic effect, in contrast to B. asper venom, here shown to contain abundant Asp49- and Lys49-type PLA2s responsible for its strong myotoxic activity. Other components identified in B. ayerbei venom include bradykinin-potentiating-like peptides and proteins belonging to the C-type lectin/lectin-like, serine proteinase, l-amino acid oxidase, disintegrin, cysteine-rich secretory protein, nerve growth factor, and phosphodiesterase families. The venom composition of B. ayerbei resembles that of neonate specimens of B. asper, which shows a predominance of metalloproteinases, with only low amounts of PLA2s. Therefore, the present findings suggest that the expression of venom proteins in B. ayerbei, in contrast to B. asper, might retain a marked 'paedomorphic' condition. Altogether, the proteomic and toxicological characterization of the venom of B. ayerbei here reported argues in favor of its taxonomical separation from B. asper in Cauca, Colombia. BIOLOGICAL SIGNIFICANCE: B. ayerbei, a pitviper found in Cauca, Colombia, had been considered as a variant form of B. asper, but was recently described as a new species on the basis of subtle morphological differences. Our study provides the first detailed proteomic and functional analysis of the venom of B. ayerbei, revealing striking interspecific variation from B. asper, thus arguing in favor of their taxonomical separation. In addition, the observed composition of the venom of B. ayerbei correlates well with its functional and toxicological properties, helping to predict the main clinical manifestations in envenomings by this species, which inflicts a considerable number of snakebites in the Southwestern regions of Colombia. PMID- 24231111 TI - An interesting cause of neonatal feed intolerance. PMID- 24231110 TI - Fermentation and proteome profiles of Lactobacillus plantarum strains during growth under food-like conditions. AB - This study aimed at investigating the proteomic adaptation of Lactobacillus plantarum strains. Cultivation of L. plantarum strains under food-like conditions (wheat flour hydrolyzed, whey milk, tomato juice) affected some metabolic traits (e.g., consumption of carbohydrates and synthesis of organic acids) compared to de Man, Rogosa and Sharpe (MRS) broth. The analysis of the fermentation profile showed that the highest number of carbon sources metabolized by L. plantarum strains was found using cells cultivated in media containing low concentration of glucose or no glucose at all. The proteomic maps of the strains were comparatively determined after growth on MRS broth and under food-like conditions. The amount of proteins depended on strain and, especially, on culture conditions. Proteins showing decreased or increased amounts under food-like conditions were identified using MALDI-TOF-MS/MS or LC-nano-ESI-MS/MS. Changes of the proteome concerned proteins that are involved in carbohydrate transport and metabolism, energy metabolism, Sec-dependent secretion system, stress response, nucleotide metabolism, regulation of nitrogen metabolism, and protein biosynthesis. A catabolic repression by glucose on carbohydrate transport and metabolism was also found. The characterization of the proteomes in response to changing environmental conditions could be useful to get L. plantarum strains adapted for specific applications. BIOLOGICAL SIGNIFICANCE: Microbial cell performance during food biotechnological processes has become one of the greatest concerns all over the world. L. plantarum is a lactic acid bacterium with a large industrial application for fermented foods or functional foods (e.g., probiotics). The present study compared the fermentation and proteomic profiling of L. plantarum strains during growth under food-like conditions and under optimal laboratory conditions (MRS broth). This study provides specific mechanisms of proteomic adaptation involved in the microbial performances (carbohydrates utilization, energy metabolism, stress resistance, etc.) affecting the main biotechnological tracts of L. plantarum strains. The finding of this study provides evidences that may be exploited to get strains adapted for specific applications in food biotechnology. PMID- 24231112 TI - Fifteen-minute consultation: structured approach to management of a child with recurrent croup. AB - Recurrent croup is a distinct clinical entity from viral croup. It is not a specific diagnosis and its presence should alert the clinician to explore the underlying cause. We discuss an evidence-based structured approach to management of a child with recurrent croup. PMID- 24231113 TI - Neonatal Sigmoid Colon Perforation: A Rare Occurrence in Low Anorectal Malformation and Review of the Literature. AB - Gastrointestinal perforation in neonates with anorectal malformation (ARM) is extremely uncommon. Delayed patient presentation is an important causative factor. A 2.5-kg neonate presented 72 hours after birth with abdominal distention and absent anal opening with meconium pearls. An abdominal X-ray revealed the presence of free gas. After adequate resuscitation patient underwent surgery. Closure of the sigmoid colon perforation with a proximal diverting loop colostomy with anoplasty was done. The literature reveals only two cases of sigmoid colon perforation with low ARM. Ours is the third case, in whom repair of the perforation and correction of the ARM was managed successfully at the same time. PMID- 24231114 TI - Arsenic, cadmium, lead, and aluminium concentrations in human milk at early stages of lactation. AB - BACKGROUND: Human milk is considered to be the best nutrition for all infants because it provides the optimal source of nutritional, immunological, developmental, psychological, economic, practical, and environmental benefits in both the short and long terms. To the best of our knowledge, few studies in Taiwan have examined the toxicant levels in breast milk and associated factors. METHODS: The research was carried out over a 6-month period. Forty-five healthy lactating women, who delivered full-term newborns at our maternity ward, were recruited, and all participants had been living in coastal urban areas of mid Taiwan for at least 3 years. One hundred and eighty human milk samples were collected on four occasions, which were classified into four lactation stages as follows: colostrums, transitional milk, early mature milk, and mature milk. RESULTS: We found that lead, cadmium, aluminium, and arsenic concentrations were the highest in colostrums: 13.22 +/- 3.58 ng/mL, 1.37 +/- 0.94 ng/mL, 56.45 +/- 22.77 ng/mL, and 1.50 +/- 1.50 ng/mL, respectively. The results of lead, cadmium, aluminium, and arsenic determination in human milk samples demonstrated a trend of decline of microelement concentrations with advancing stages of lactation. We found that the infants of smoking mothers were exposed to more cadmium than infants of nonsmoking mothers (p < 0.05). CONCLUSION: According to our findings, frequent routine sampling of breast milk is worthwhile. Prevention strategies including behavior modification and education on proper nutrition should be provided to women who are at high risk of toxicant exposure. In summary, breastfeeding is still generally encouraged and recommended. PMID- 24231115 TI - Learning to predict: exposure to temporal sequences facilitates prediction of future events. AB - Previous experience is thought to facilitate our ability to extract spatial and temporal regularities from cluttered scenes. However, little is known about how we may use this knowledge to predict future events. Here we test whether exposure to temporal sequences facilitates the visual recognition of upcoming stimuli. We presented observers with a sequence of leftwards and rightwards oriented gratings that was interrupted by a test stimulus. Observers were asked to indicate whether the orientation of the test stimulus matched their expectation based on the preceding sequence. Our results demonstrate that exposure to temporal sequences without feedback facilitates our ability to predict an upcoming stimulus. In particular, observers' performance improved following exposure to structured but not random sequences. Improved performance lasted for a prolonged period and generalized to untrained stimulus orientations rather than sequences of different global structure, suggesting that observers acquire knowledge of the sequence structure rather than its items. Further, this learning was compromised when observers performed a dual task resulting in increased attentional load. These findings suggest that exposure to temporal regularities in a scene allows us to accumulate knowledge about its global structure and predict future events. PMID- 24231116 TI - Bayesian evaluation of budgets for endemic disease control: An example using management changes to reduce milk somatic cell count early in the first lactation of Irish dairy cows. AB - The aim of this research was to determine budgets for specific management interventions to control heifer mastitis in Irish dairy herds as an example of evidence synthesis and 1-step Bayesian micro-simulation in a veterinary context. Budgets were determined for different decision makers based on their willingness to pay. Reducing the prevalence of heifers with a high milk somatic cell count (SCC) early in the first lactation could be achieved through herd level management interventions for pre- and peri-partum heifers, however the cost effectiveness of these interventions is unknown. A synthesis of multiple sources of evidence, accounting for variability and uncertainty in the available data is invaluable to inform decision makers around likely economic outcomes of investing in disease control measures. One analytical approach to this is Bayesian micro simulation, where the trajectory of different individuals undergoing specific interventions is simulated. The classic micro-simulation framework was extended to encompass synthesis of evidence from 2 separate statistical models and previous research, with the outcome for an individual cow or herd assessed in terms of changes in lifetime milk yield, disposal risk, and likely financial returns conditional on the interventions being simultaneously applied. The 3 interventions tested were storage of bedding inside, decreasing transition yard stocking density, and spreading of bedding evenly in the calving area. Budgets for the interventions were determined based on the minimum expected return on investment, and the probability of the desired outcome. Budgets for interventions to control heifer mastitis were highly dependent on the decision maker's willingness to pay, and hence minimum expected return on investment. Understanding the requirements of decision makers and their rational spending limits would be useful for the development of specific interventions for particular farms to control heifer mastitis, and other endemic diseases. PMID- 24231117 TI - Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer--a real-world, prospective, observational French study: PReOBS. AB - INTRODUCTION: Data on the epidemiology and prevention of venous thromboembolism in patients undergoing abdominal or pelvic cancer surgery in real practice are limited. The primary objective of this observational study was to describe the thromboprophylactic strategy implemented in routine practice. The main secondary objective was to assess the incidence of outcomes. MATERIALS AND METHODS: Patients admitted to public or private hospitals for abdominal or pelvic cancer surgery were included between November 2009 and November 2010; endoscopic route for surgery was the only exclusion criterion. Study outcomes were recorded at hospital discharge and at routine follow-up (generally 9+/-3weeks). RESULTS: 2380 patients (mean+/-SD age: 66.4+/-11.6years, women: 36.8%) admitted to hospital for abdominal (47.8%), urological (41%), or gynaecological (11.2%) cancer surgery were included in the analysis. Of these, 2179 had data available at study end. Perioperative antithrombotic prophylaxis, consisting mainly of low-molecular weight heparin, was given to 99.5% of patients. At hospital discharge, thromboprophylaxis was continued in 91.7% of patients, 57.4% receiving a 4-6week prophylaxis. This management strategy was associated with an overall venous thromboembolic event rate of 1.9%, 34.7% of events occurring after discharge. Incidences of fatal bleeding, bleeding in a critical organ and bleeding necessitating re-intervention were 0.1%, 0.3% and 1.7%, respectively. Overall mortality was 1.5%. CONCLUSIONS: Thromboprophylaxis is routinely used in French patients undergoing major cancer surgery. For more than a third of patients, however, treatment duration did not comply with best-practice recommendations, which might explain the non-negligible rate of thromboembolic complications still observed in this patient population. PMID- 24231118 TI - Decreased Tim-3 and its correlation with Th1 cells in patients with immune thrombocytopenia. AB - Here we evaluate the expression of Tim-3 in CD4+ T cells from patients with immune thrombocytopenia (ITP). We also counted platelets and evaluated plasma IFN gamma, IL-18 and IL-4 levels in patients with active ITP (n=26), patients with ITP in remission (n=23) and in healthy subjects (n=34) by enzyme linked immunosorbent assay (ELISA). Using real-time quantitative polymerase chain reaction (RT-PCR), the mRNA expression of IL-18, IFN-gamma, IL-4, T-box (T-bet) and Tim-3 was studied in the blood. The CD4+ Tim-3+ cells in blood were evaluated by flow cytometry and are expressed as a percentage of the total number of CD4+ cells. The Tim-3 positive cells within the circulating CD4+ population of newly diagnosed patients were significantly decreased compared to controls. However, T bet, IL-18 and IFN-gamma levels were significantly elevated in patients. Tim-3 mRNA expression was significantly lower in the peripheral mononuclear cells (PBMCs) of ITP patients compared to controls. The decreased levels of Tim-3 during active stages of disease suggest a possible role in the pathogenesis and course of ITP and restoration of Tim-3 may be a reasonable therapeutic strategy for ITP. PMID- 24231119 TI - Review of machine learning and signal processing techniques for automated electrode selection in high-density microelectrode arrays. AB - Recently developed CMOS-based microprobes contain hundreds of electrodes on a single shaft with interelectrode distances as small as 30 um. So far, neuroscientists manually select a subset of those electrodes depending on their appraisal of the "usefulness" of the recorded signals, which makes the process subjective but more importantly too time consuming to be useable in practice. The ever-increasing number of recording electrodes on microelectrode probes calls for an automated selection of electrodes containing "good quality signals" or "signals of interest." This article reviews the different criteria for electrode selection as well as the basic signal processing steps to prepare the data to compute those criteria. We discuss three of them. The first two select the electrodes based on "signal quality." The first criterion computes the penalized signal-to-noise ratio (SNR); the second criterion models the neuroscientist's appraisal of signal quality. Last, our most recent work allows the selection of electrodes that capture particular anatomical cell types. The discussed algorithms perform what is called in the literature "electronic depth control" in contrast to the mechanical repositioning of the electrode shafts in search of "good quality signals" or "signals of interest." PMID- 24231120 TI - Challenges to free will: transgenerational epigenetic information, unconscious processes, and vanishing twin syndrome. AB - Here, we present various research results and thoughts with the intention of challenging notions about free choice. Namely, we describe the concept of transgenerational transmission of epigenetic information and discuss its non conscious effects on cognitive abilities, behavioral and emotional patterns, and responses with regard to one's life and decisions, and the impact these have on the concept of free will. In addition, we discuss the essential role of unconscious mechanisms in human decision processes. We also show that twin loss in the womb can have a powerful lifelong impact on the surviving twin through non conscious context-dependent epigenetic changes. Finally, we hypothesize that human explicit self-consciousness may be an active executer that intermediates between unconsciousness and the external environment by means of feedback and feed-forward interactions. This executive function makes it possible for self consciousness to continuously develop in self-organized evolution. PMID- 24231121 TI - Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient's risk. AB - The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction. PMID- 24231122 TI - Characterization of a type D1A EUL-related lectin from rice expressed in Pichia pastoris. AB - OrysaEULD1A is one of the five EUL genes in rice (Oryza sativa) encoding a putative carbohydrate-binding protein belonging to the family of Euonymus related lectins (EUL). The OrysaEULD1A sequence comprises two highly similar EUL domains (91% sequence similarity and 72% sequence identity) separated by a 23 amino acid linker sequence and preceded by a 19 amino acid N-terminal sequence. In the present study, the full-length protein OrysaEULD1A as well as its individual domains OrysaEULD1A domain 1 and 2 were expressed in Pichia pastoris. After purification of the recombinant proteins, their carbohydrate-binding specificity was analyzed and compared. Interestingly, all recombinant lectins showed clear specificity towards galactosylated structures. Furthermore, all recombinant proteins agglutinated red blood cells, indicating that the full-length protein OrysaEULD1A and its domains are true lectins. These results taken together with data previously reported for single-domain EUL proteins indicate that although the amino acids--responsible for the formation of the carbohydrate-binding site- are identical for all EUL proteins in rice, these lectins show different carbohydrate specificities. This promiscuity of the carbohydrate-binding site can be attributed to gene divergence. PMID- 24231124 TI - Undetected creatinine levels. PMID- 24231123 TI - The obsessive-compulsory clinical pathologist. PMID- 24231125 TI - Hepcidin levels in chronic hemodialysis patients: a critical evaluation. AB - Altered systemic iron metabolism is a key element of uremia, and functional iron deficiency mainly related to subclinical inflammation makes it difficult to maintain proper control of anemia in chronic hemodialysis patients (CHD). In the last decade, the hepatic hormone hepcidin has been progressively recognized as the master regulator of circulating iron levels through the modulation of cellular iron fluxes in response to iron stores, as well as to erythroid and inflammatory stimuli. Hepcidin is cleared by the kidney and progression of renal disease has been associated to increased serum hepcidin levels. This, in turn, reduces iron availability for erythropoiesis, suggesting anti-hepcidin strategies for improving anemia control. Moreover, hepcidin has been recently implicated in the pathogenesis of long-term complications of dialysis, like accelerated atherosclerosis. Initial studies almost invariably reported a sustained increase of serum hepcidin in chronic hemodialysis patients. Noteworthy, such studies included relatively few patients and controls that were poorly matched for major determinants of serum hepcidin at population level, i.e., age and gender. More recent data based on accurately matched larger series challenge the view that hepcidin is intrinsically increased in hemodialysis patients, showing a marked inter- and intra-individual variability of hormone levels. Here we take a critical look to the data published so far on hepcidin levels in CHD, analyze the reasons underlying the discrepancies in available studies and the hepcidin variability in CHD, and point out the need for further studies in large series of well-characterized CHD patients and controls. PMID- 24231126 TI - A simple and precise method for direct measurement of fractional esterification rate of high density lipoprotein cholesterol by high performance liquid chromatography. AB - BACKGROUND: The relationship between fractional cholesterol esterification rate in plasma or serum high-density lipoprotein (HDL) (FER(HDL)) and lipoprotein subfractions and other cardiovascular disease (CVD) risk factors has been demonstrated. However, the current method for measuring FER(HDL) requires fresh serum samples and radioactive labeling of the samples, making it impractical for use in clinical laboratories. In this study, we developed a simple and precise HPLC method for the measurement of FER(HDL). Correlations between FER(HDL) and CVD risk factors were evaluated in 119 healthy volunteers. METHODS: Fasting blood samples were collected and serum was isolated within 2 h. Serum HDL was prepared by precipitation of apolipoprotein B (apoB)-containing lipoproteins with dextran sulfate and magnesium chloride. HDL fractions were divided into two aliquots and incubated at 0 degrees C and 37 degrees C, respectively, for 1 h. Free cholesterol in the HDL fractions was analyzed by HPLC. FER(HDL) was calculated as the percent decrease of free cholesterol during incubation. RESULTS: The esterification reaction of HDL free cholesterol was not linear, but the measured FER(HDL) was stable when serum samples were stored at room temperature for <4 h, or at 4 degrees C for <24 h. The intra-assay and total CVs for FER(HDL) measurements were 1.0%-2.1% and 1.6%-3.8%, respectively. Results of 119 healthy volunteers showed that FER(HDL) was positively correlated with age, BMI, blood pressure, total cholesterol (TC), triglyceride (TG) and small dense low-density lipoprotein-cholesterol (LDLb-C), and negatively correlated with HDL-C and HDL2 C. FER(HDL) has shown to be a predictor of HDL and LDL subfraction distributions. CONCLUSIONS: This method is simple, non-radioactive and precise and will be useful in prediction of lipoprotein subfraction distributions and in clinical assessment of CVD risks. PMID- 24231127 TI - Crohn's disease specific pancreatic antibodies: clinical and pathophysiological challenges. AB - Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBD-specific humoral markers of autoimmunity in the form of autoantibodies have been reported first in the late 1950s by demonstrating the occurrence of autoimmunity in UC, while humoral autoimmunity in CrD can be traced back to the 1970s. Ever since, the pathophysiological role of autoimmune responses in IBDs has remained poorly understood. Notwithstanding, autoreactive responses play a major role in inflammation leading to overt IBD. In CrD, approximately 40% of patients and <20% of patients with UC demonstrate loss of tolerance to antigens of the exocrine pancreas. Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. The previously unsolved contradiction of pancreatic autoreactivity and intestinal inflammation in IBD was elucidated by demonstrating the expression of GP2 at the site thereof. Intriguingly, GP2 has been reported to be a receptor on microfold cells of intestinal Peyer's patches, which are believed to represent the origin of CrD inflammation. The development of immunoassays for the detection of antibodies to GP2 has paved the way to investigate the association of such antibodies with the clinical phenotype in CrD. Given the recently discovered immunomodulating role of GP2 in innate and adaptive intestinal immunity, this association can shed further light on the pathophysiology of IBD. In this context, the association of anti-GP2 autoantibodies as novel CrD-specific markers with the clinical phenotype in CrD will be discussed in this review. PMID- 24231128 TI - Differentiation and identification of filamentous fungi by high-throughput FTIR spectroscopic analysis of mycelia. AB - Routine identification of fungi based on phenotypic and genotypic methods can be fastidious and time-consuming. In this context, there is a constant need for new approaches allowing the rapid identification of molds. Fourier-transform infrared (FTIR) spectroscopy appears as such an indicated method. The objective of this work was to evaluate the potential of FTIR spectroscopy for an early differentiation and identification of filamentous fungi. One hundred and thirty one strains identified using DNA sequencing, were analyzed using FTIR spectroscopy of the mycelia obtained after a reduced culture time of 48 h compared to current conventional methods. Partial least square discriminant analysis was used as a chemometric method to analyze the spectral data and for identification of the fungal strains from the phylum to the species level. Calibration models were constructed using 106 strains pertaining to 14 different genera and 32 species and were used to identify 25 fungal strains in a blind manner. Identification levels of 98.97% and 98.77% achieved were correctly assigned to the genus and species levels respectively. FTIR spectroscopy with its high discriminating power and rapidity therefore shows strong promise for routine fungal identification. Upgrading of our database is ongoing to test the technique's robustness. PMID- 24231129 TI - Planned and reactive agility performance in semiprofessional and amateur basketball players. AB - CONTEXT: Research indicates that planned and reactive agility are different athletic skills. These skills have not been adequately assessed in male basketball players. PURPOSE: To define whether 10-m-sprint performance and planned and reactive agility measured by the Y-shaped agility test can discriminate between semiprofessional and amateur basketball players. METHODS: Ten semiprofessional and 10 amateur basketball players completed 10-m sprints and planned- and reactive-agility tests. The Y-shaped agility test involved subjects sprinting 5 m through a trigger timing gate, followed by a 45 degrees cut and 5 m sprint to the left or right through a target gate. In the planned condition, subjects knew the cut direction. For reactive trials, subjects visually scanned to find the illuminated gate. A 1-way analysis of variance (P < .05) determined between-groups differences. Data were pooled (N = 20) for a correlation analysis (P < .05). RESULTS: The reactive tests differentiated between the groups; semiprofessional players were 6% faster for the reactive left (P = .036) and right (P = .029) cuts. The strongest correlations were between the 10-m sprints and planned-agility tests (r = .590-.860). The reactive left cut did not correlate with the planned tests. The reactive right cut moderately correlated with the 10-m sprint and planned right cut (r = .487-.485). CONCLUSIONS: The results reemphasized that planned and reactive agility are separate physical qualities. Reactive agility discriminated between the semiprofessional and amateur basketball players; planned agility did not. To distinguish between male basketball players of different ability levels, agility tests should include a perceptual and decision-making component. PMID- 24231130 TI - Mechanical and non-mechanical functions of Dystrophin can prevent cardiac abnormalities in Drosophila. AB - Dystrophin-deficiency causes cardiomyopathies and shortens the life expectancy of Duchenne and Becker muscular dystrophy patients. Restoring Dystrophin expression in the heart by gene transfer is a promising avenue to explore as a therapy. Truncated Dystrophin gene constructs have been engineered and shown to alleviate dystrophic skeletal muscle disease, but their potential in preventing the development of cardiomyopathy is not fully understood. In the present study, we found that either the mechanical or the signaling functions of Dystrophin were able to reduce the dilated heart phenotype of Dystrophin mutants in a Drosophila model. Our data suggest that Dystrophin retains some function in fly cardiomyocytes in the absence of a predicted mechanical link to the cytoskeleton. Interestingly, cardiac-specific manipulation of nitric oxide synthase expression also modulates cardiac function, which can in part be reversed by loss of Dystrophin function, further implying a signaling role of Dystrophin in the heart. These findings suggest that the signaling functions of Dystrophin protein are able to ameliorate the dilated cardiomyopathy, and thus might help to improve heart muscle function in micro-Dystrophin-based gene therapy approaches. PMID- 24231131 TI - Denosumab: a cost-effective alternative for older men with osteoporosis from a Swedish payer perspective. AB - OBJECTIVE: To assess the cost-effectiveness of denosumab versus other treatments in men with osteoporosis who are >=75years old from a payer perspective in Sweden. METHODS: A lifetime cohort Markov model was developed with seven health states: well, hip fracture, vertebral fracture, other osteoporotic fracture, post hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Estimates of fracture efficacy were drawn from available studies in post-menopausal osteoporotic (PMO) women as BMD improvements have been shown to be similar across male osteoporosis (MOP) and PMO populations, and a recent clinical trial suggested that the fracture risk reduction from bisphosphonate therapy in men is similar to that seen in women in comparable studies. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, ibandronate, zoledronate, strontium ranelate and teriparatide. On average, patients in the model were 78years old, with bone mineral density T score at the femoral neck of -2.12. Prevalent vertebral fractures were present in 23% of patients. In the base-case, the model assumed that patients would experience treatment-related effects up to 2years after discontinuation. Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. RESULTS: Total lifetime costs for denosumab, alendronate, strontium ranelate, zoledronate, risedronate, ibandronate and teriparatide were ?31,004, ?33,731, ?34,788, ?34,796, ?34,826, ?35,983 and ?37,461, respectively. Total QALYs were 5.23, 5.15, 5.15, 5.17, 5.13, 5.12 and 5.22, respectively. Compared to other treatments, denosumab had the lowest costs and highest QALYs. In the one way sensitivity analyses, when compared to alendronate (next least expensive strategy), the ICER for denosumab was most sensitive to the relative risk of hip fracture on denosumab. The probability of denosumab being cost-effective compared to the other treatments at a threshold of ?66,000/QALY was 96.1%. CONCLUSION: Denosumab dominated all comparators, including generic bisphosphonates, in the treatment of osteoporosis in men who were >=75years old in Sweden. PMID- 24231132 TI - Density functional theory study on the interactions of L-cysteine with graphene: adsorption stability and magnetism. AB - Understanding the interactions between graphene and biomolecules is of fundamental relevance to the area of nanobiotechnology. Herein, we take l cysteine as the probe biomolecule and investigate its adsorption on pristine graphene and B-, N-, Al-, Ni-, Ga-, Pd-doped graphene using density functional theory calculations. Three kinds of upright adsorption configurations, via unprotonated functional groups (-SH, -NH2, -COOH), are considered. The calculations reveal pristine graphene physically adsorbs l-cysteine. N-doped graphene shows physisorption towards the S-end and N-end l-cysteine, and chemisorption towards the O-end radical. Strong chemisorption, with site-specific preference, occurs on Al-, Ni-, Ga- and Pd-doped graphene, accompanied by severe structural changes. Spin polarization with an unusual mirror symmetry on Ni- and Pd-doped graphene is induced by chemisorption of unprotonated l-cysteine, except for O-end adsorption on Pd-doped graphene. The magnetization arises mainly from spin polarization of the C 2pz orbital, with a minor magnetism located on Ni or Pd. The influence of van der Waals forces is also evaluated. A thorough analysis of the adsorption stability and magnetism of these systems would be beneficial to facilitate applications in graphene-based biosensing, biomolecule immobilization, magnetic bio-separation and other fields in bionanotechnology. PMID- 24231133 TI - Regulation of human mesenchymal stem cells differentiation into chondrocytes in extracellular matrix-based hydrogel scaffolds. AB - To induce human mesenchymal stem cells (hMSCs) to differentiate into chondrocytes in three-dimensional (3D) microenvironments, we developed porous hydrogel scaffolds using the cartilage extracellular matrix (ECM) components of chondroitin sulfate (CS) and collagen (COL). The turbidity and viscosity experiments indicated hydrogel could form through pH-triggered co-precipitation when pH=2-3. Enzyme-linked immunosorbent assay (ELISA) confirmed the hydrogel scaffolds could controllably release growth factors as envisaged. Transforming growth factor-beta (TGF-beta) was released to stimulate hMSCs differentiation into chondrocytes; and then collagen binding domain-basic fibroblast growth factor (CBD-bFGF) was released to improve the differentiation and preserve the chondrocyte phenotype. In in vitro cell culture experiments, the differentiation processes were compared in different microenvironments: 2D culture in culture plate as control, 3D culture in the fabricated scaffolds without growth factors (CC), the samples with CBD-bFGF (CC-C), the samples with TGF-beta (CC-T), the samples with CBD-bFGF/TGF-beta (CC-CT). Real-time polymerase chain reaction (RT PCR) revealed the hMSC marker genes of CD44 and CD105 decreased; at the same time the chondrocyte marker genes of collagen type II and aggrecan increased, especially in the CC-CT sample. Immunostaining results further confirmed the hMSC marker protein of CD 44 disappeared and the chondrocyte marker protein of collagen type II emerged over time in the CC-CT sample. These results imply the ECM-based hydrogel scaffolds with growth factors can supply suitable 3D cell niches for hMSCs differentiation into chondrocytes and the differentiation process can be regulated by the controllably released growth factors. PMID- 24231134 TI - Comparison of robotic-assisted vs conventional laparoscopy for extraperitoneal paraaortic lymphadenectomy. AB - OBJECTIVE: To evaluate the perioperative outcomes of robotic-assisted extraperitoneal paraaortic lymphadenectomy for locally advanced cervical cancer and to compare to a previous series of patients from our institution undergoing the same procedure by conventional laparoscopy. METHODS: 17 patients with locally advanced cervical cancer (FIGO stages IB2, IIA2 and IIB-IVA) underwent pretherapeutic extraperitoneal paraaortic lymphadenectomy by robotic-assisted laparoscopy. Perioperative outcomes including age, BMI, FIGO stage, operating time, blood loss, complications and length of hospital stay were compared to a series of 83 patients from our institution undergoing the same procedure by conventional laparoscopy. RESULTS: The median values for operating time and hospital days for the robotic-assisted and conventional laparoscopy groups were 150 vs. 150 min and 2 vs 2 days, respectively. In the robotic group, blood loss was lower (90 vs 20 ml, p<0.05) and more aortic nodes were removed (14 vs 17 nodes, p<0.05). Docking time was 7 min (range 3-15). There were no intraoperative complications. There were no differences for postoperative complications (17.6% vs 8.4%). CONCLUSION: Robotic-assisted and conventional laparoscopy provide similar perioperative outcomes other than lower blood loss and higher number of aortic nodes removed (both without clinical impact) in robotic patients for the performance of extraperitoneal paraaortic lymphadenectomy in patients with locally advanced cervical cancer. We believe that robotic surgery is an additional tool to perform the same surgical procedure. HIGHLIGHTS: Robotic assisted and conventional laparoscopic extraperitoneal paraaortic lymphadenectomy provide similar perioperative outcomes. PMID- 24231135 TI - Effect of low-intensity ergometer aerobic training on glucose tolerance in severely impaired nondiabetic stroke patients. AB - OBJECTIVE: To investigate whether low-intensity ergometer aerobic training has beneficial effect on glucose tolerance in nondiabetic patients with severely impaired stroke. METHODS: Fifty-four severely impaired stroke survivors were recruited and randomly assigned to the experimental group and control group. They have no diabetes history with fasting plasma glucose less than 7 mmol/L. Both groups participated in a 6-week rehabilitation training program with low intensity ergometer aerobic training added only in the experimental group 3 times per week. Primary outcome variables were fasting glucose, fasting insulin, 2-hour glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) in oral glucose tolerance test before and after intervention. RESULTS: Before intervention, 36 of 54 (66.7%) were diagnosed with impaired glucose status or diabetic glucose tolerance totally. The average 2-hour plasma glucose level was 9.14 +/- 1.39 mmol/L. After intervention, aerobic training significantly improved fasting insulin (from 8.51 +/- 2.01 MUU/mL to 7.11 +/- 2.02 MUU/mL), 2-hour glucose level (from 9.13 +/- 1.14 mmol/L to 7.22 +/- 1.23 mmol/L), and HOMA-IR (from 1.62 +/- 1.01 to 1.29 +/- .79) in the intervention group compared with the control group (P < .05). Aerobic training also significantly improved their glucose tolerance state (P < .05). CONCLUSIONS: Preliminary findings suggest that abnormal glucose tolerance may be highly present among severely impaired nondiabetic stroke patients and low-intensity ergometer aerobic training may have beneficial role in improving glucose tolerance. PMID- 24231136 TI - Outcome of cervicocranial artery dissection with different treatments: a systematic review and meta-analysis. AB - OBJECTIVE: The purpose of this meta-analysis is to compare clinical outcomes between endovascular treatment and conservative treatment for cervicocranial artery dissection. METHODS: Medline, Embase, and Cochrane Library databases were searched for studies comparing endovascular treatment versus conservative treatment for cervicocranial artery dissection patients. The period searched was from November 1994 to March 2013. Fifteen observational studies involving 442 cervicocranial artery dissection patients were found. Evaluated outcomes included rate of mortality, disability, and good recovery. The rebleeding rate in subarachnoid hemorrhage (SAH) patients was also recorded and compared. RESULTS: In general, patients who received endovascular treatment enjoyed a lower mortality rate than those who received conservative treatment (P = .02, odds ratio [OR]: .5, 95% confidence interval [CI]: .27-.90), especially patients having ruptured cervicocranial artery dissection (P = .002, OR: .32, 95% CI .15 .66) and dissecting aneurysms (P = .006, OR: .31, 95% CI .14-.71). Among SAH patients with a Hunt-Hess score of 3 or more, endovascular treatment decreased mortality significantly (P = .006, OR: .22, 95% CI .08-.65), whereas no significant differences between these 2 treatments occurred in patients having a Hunt-Hess score less than 3. CONCLUSIONS: Endovascular treatment yields a better outcome, with greater benefit in patients with ruptured cervicocranial artery dissection, dissecting aneurysms, and a Hunt-Hess score of 3 or more. Randomized controlled trials comparing these 2 therapeutic strategies are needed. PMID- 24231137 TI - Profile of patients with cerebral venous sinus thrombosis with cerebellar involvement. AB - BACKGROUND: Cerebral venous thrombosis (CVT) is a rare form stroke with diverse manifestations. There is very little information available regarding profile of patients with cerebellar involvement in CVT. We describe the clinical profile, investigations, and outcome of patients with cerebellar involvement with CVT. METHODS: We prospectively studied 6 (male:female: 5:1, mean age 29.3 +/- 10.3 years) patients of CVT with cerebellar involvement (2 isolated cerebellar and 4 associated deep or supratentorial structures) among 330 CVT patients (1.8%) admitted in our stroke unit during a period of 3 years. RESULTS: The presenting features (mean duration 7.0 +/- 4.7 days) were headache, vomiting, encephalopathy, ataxia, and papilledema. Initial diagnosis considered were neuroinfection in 2 patients, raised intracranial pressure in 2, subarachnoid hemorrhage in 1, and subacute ataxia in 1 patient. Computed tomography (CT) was diagnostic in 3 of 5 patients, whereas magnetic resonance imaging (MRI) and magnetic resonance venography were diagnostic in all; in addition, MRI was superior in detecting new lesions not visualized on CT, in better delineating hemorrhages and in predicting the age of thrombus. Patients were managed medically with anticoagulation, anti-edema, and anti-epileptics and supportive treatment. Two patients underwent posterior fossa decompression. Four patients made complete recovery at the time of discharge and 2 patients died (1 because of brain stem dysfunction and another because of postoperative pneumonia and septicemia). CONCLUSIONS: Cerebellar involvement in CVT is very rare, and high index of suspicion is required for diagnosis. Imaging with CT and MRI will help in confirming the diagnosis. Conventional anticoagulation is effective in treatment. Mortality was 33%, and there was no disability in survivors. PMID- 24231138 TI - Favorable functional recovery in overweight ischemic stroke survivors: findings from the China National Stroke Registry. AB - BACKGROUND: Obesity paradox has been reported because of the inverse relationship between the body mass index (BMI) and mortality in stroke patients. The relationship between BMI and functional recovery in stroke survivors is less well established. We explored the impact of BMI on functional recovery and mortality in stroke patients in the China National Stroke Registry (CNSR). METHODS: Patients were consecutively recruited based on a standard protocol and prospectively followed up for outcomes at 3 months after disease onset. Patients were divided into 5 groups according to their BMI: underweight (<18.5 kg/m(2)), normal weight (18.5-22.9 kg/m(2)), overweight (23-27.4 kg/m(2)), obese (27.5-32.4 kg/m(2)), or severely obese (>=32.5 kg/m(2)). Multivariate logistic regression was performed to analyze the association between BMI and functional recovery or mortality. RESULTS: CNSR enrolled 22,216 patients hospitalized for acute cerebrovascular events, and 10,905 eligible acute ischemic stroke patients were analyzed in our study. Favorable functional recovery (modified Rankin Scale score 0-1) was seen in 52.4% of underweight, 55.0% of normal weight, 61.0% of overweight, 59.2% of obese, and 60.3% of severely obese stroke survivors (P < .001). Overweight was independently associated with favorable 3-month functional recovery (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.12-1.38). Mortality rate was 14.9% in underweight, 7.8% in normal weight, 7.1% in overweight, 7.2% in obese, and 11.5% in severely obese patients (P < .001). Severe obesity was independently associated with higher 3-month mortality (OR 2.01; 95% CI 1.10-3.69). CONCLUSIONS: The stroke obesity paradox can be extended to include functional recovery but should not be interpreted as the fatter the better. PMID- 24231139 TI - Ischemic stroke as the first manifestation of hepatic epithelioid hemangioendothelioma. AB - A 38-year-old obese woman, with a past medical history of cholecystectomy and dyslipidaemia, presented with acute occipital headache, vomiting and rotational vertigo which lasted 8 hours. On admission neurological examination was unremarkable, however general physical examination revealed hepatomegaly. Routine blood tests showed abnormal liver function tests. MRI scan indicated an acute ischemic infarct in the right cerebellum. Extensive investigation was negative. However, liver MRI revealed multiple lesions in both liver lobes. Ultrasound guided liver biopsy and histopathological analysis confirmed the diagnosis of hepatic hemangioendothelioma. In conclusion, hypercoaguable state related to hepatic epithelioid hemangioendothelioma can lead to an ischemic stroke, as a rare first manifestation of the disease. PMID- 24231140 TI - Network hubs in the human brain. AB - Virtually all domains of cognitive function require the integration of distributed neural activity. Network analysis of human brain connectivity has consistently identified sets of regions that are critically important for enabling efficient neuronal signaling and communication. The central embedding of these candidate 'brain hubs' in anatomical networks supports their diverse functional roles across a broad range of cognitive tasks and widespread dynamic coupling within and across functional networks. The high level of centrality of brain hubs also renders them points of vulnerability that are susceptible to disconnection and dysfunction in brain disorders. Combining data from numerous empirical and computational studies, network approaches strongly suggest that brain hubs play important roles in information integration underpinning numerous aspects of complex cognitive function. PMID- 24231141 TI - Determination of trichothecenes A (T-2 toxin, HT-2 toxin, and diacetoxyscirpenol) in the tissues of broilers using liquid chromatography coupled to tandem mass spectrometry. AB - A stable and sensitive method has been developed for use in food and livestock product safety for the detection of mycotoxins. This newly developed method allows for the determination of T-2 toxin, HT-2 toxin and diacetoxyscirpenol (DAS) in heart, liver, spleen, lung, kidney, Glandular stomach, muscular stomach, small intestine, muscle, bone and brain samples from broilers using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The samples were initially extracted with ethyl acetate before being filtered through a 0.22MUm nylon syringe filter and subjected to chromatographic separation on a reversed phase C18 (50*2.1mm, 3MUm) column. A mobile phase composed of 0.1% acetic acid and 10mM ammonium acetate in methanol and water was used in an assay of the levels of T-2 toxin, HT-2 toxin and DAS. For the analysis of the target compounds, the mass spectrometer was operated under positive electrospray ionization conditions in the selected reaction monitoring mode. The limit of detection was in the range of 0.02-0.05ng/g, whereas the limit of quantification was in the range of 0.08-0.15ng/g. The extraction recoveries of spiked samples from the high, intermediate and low levels ranged from 58.5% to 110.5%, and the relative standard deviation (RSD (%)) values were less than 17.0%. The results of inter- and intra-day precision (RSD (%)) were within 14.7%. The results revealed that the present method could be successfully applied to the analysis of T-2 toxin, HT-2 toxin and DAS in the real samples. PMID- 24231142 TI - On comparison of SimTandem with state-of-the-art peptide identification tools, efficiency of precursor mass filter and dealing with variable modifications. AB - The similarity search in theoretical mass spectra generated from protein sequence databases is a widely accepted approach for identification of peptides from query mass spectra produced by shotgun proteomics. Growing protein sequence databases and noisy query spectra demand database indexing techniques and better similarity measures for the comparison of theoretical spectra against query spectra. We employ a modification of previously proposed parameterized Hausdorff distance for comparisons of mass spectra. The new distance outperforms the original distance, the angle distance and state-of-the-art peptide identification tools OMSSA and X!Tandem in the number of identified peptides even though the q-value is only 0.001. When a precursor mass filter is used as a database indexing technique, our method outperforms OMSSA in the speed of search. When variable modifications are not searched, the search time is similar to X!Tandem. We show that the precursor mass filter is an efficient database indexing technique for high-accuracy data even though many variable modifications are being searched. We demonstrate that the number of identified peptides is bigger when variable modifications are searched separately by more search runs of a peptide identification engine. Otherwise, the false discovery rates are affected by mixing unmodified and modified spectra together resulting in a lower number of identified peptides. Our method is implemented in the freely available application SimTandem which can be used in the framework TOPP based on OpenMS. PMID- 24231143 TI - Model checking software for phylogenetic trees using distribution and database methods. AB - Model checking, a generic and formal paradigm stemming from computer science based on temporal logics, has been proposed for the study of biological properties that emerge from the labeling of the states defined over the phylogenetic tree. This strategy allows us to use generic software tools already present in the industry. However, the performance of traditional model checking is penalized when scaling the system for large phylogenies. To this end, two strategies are presented here. The first one consists of partitioning the phylogenetic tree into a set of subgraphs each one representing a subproblem to be verified so as to speed up the computation time and distribute the memory consumption. The second strategy is based on uncoupling the information associated to each state of the phylogenetic tree (mainly, the DNA sequence) and exporting it to an external tool for the management of large information systems. The integration of all these approaches outperforms the results of monolithic model checking and helps us to execute the verification of properties in a real phylogenetic tree. PMID- 24231144 TI - Inter-STOP symbol distances for the identification of coding regions. AB - In this study we explore the potential of inter-STOP symbol distances for finding coding regions in DNA sequences. We use the distance between STOP symbols in the DNA sequence and a chi-square statistic to evaluate the nonhomogeneity of the three possible reading frames and the occurrence of one long distance in one of the frames. The results of this exploratory study suggest that inter-STOP symbol distances have strong ability to discriminate coding regions in prokaryotes and simple eukaryotes. PMID- 24231145 TI - Improving the performance of Transposable Elements detection tools. AB - Transposable Elements (TE) are sequences of DNA that move and transpose within a genome. TEs, as mutation agents, are quite important for their role in both genome alteration diseases and on species evolution. Several tools have been developed to discover and annotate TEs but no single tool achieves good results on all different types of TEs. In this paper we evaluate the performance of several TEs detection and annotation tools and investigate if Machine Learning techniques can be used to improve their overall detection accuracy. The results of an in silico evaluation of TEs detection and annotation tools indicate that their performance can be improved by using machine learning constructed classifiers. PMID- 24231146 TI - An evolutionary and visual framework for clustering of DNA microarray data. AB - This paper presents a case study to show the competence of our evolutionary and visual framework for cluster analysis of DNA microarray data. The proposed framework joins a genetic algorithm for hierarchical clustering with a set of visual components of cluster tasks given by a tool. The cluster visualization tool allows us to display different views of clustering results as a means of cluster visual validation. The results of the genetic algorithm for clustering have shown that it can find better solutions than the other methods for the selected data set. Thus, this shows the reliability of the proposed framework. PMID- 24231147 TI - Re-annotation of the genome sequence of Helicobacter pylori 26695. AB - Helicobacter pylori is a pathogenic bacterium that colonizes the human epithelia, causing duodenal and gastric ulcers, and gastric cancer. The genome of H. pylori 26695 has been previously sequenced and annotated. In addition, two genome-scale metabolic models have been developed. In order to maintain accurate and relevant information on coding sequences (CDS) and to retrieve new information, the assignment of new functions to Helicobacter pylori 26695s genes was performed in this work. The use of software tools, on-line databases and an annotation pipeline for inspecting each gene allowed the attribution of validated EC numbers and TC numbers to metabolic genes encoding enzymes and transport proteins, respectively. 1212 genes encoding proteins were identified in this annotation, being 712 metabolic genes and 500 non-metabolic, while 191 new functions were assignment to the CDS of this bacterium. This information provides relevant biological information for the scientific community dealing with this organism and can be used as the basis for a new metabolic model reconstruction. PMID- 24231149 TI - Coconut anaphylaxis: Case report and review. PMID- 24231148 TI - Reirradiation of the eye with plaque brachytherapy: a single institution experience report of eight consecutive patients submitted to retreatment after local relapse of malignant disease of the eye. AB - PURPOSE: To evaluate the feasibility of reirradiation of the eye with plaque brachytherapy (REPBT) for local recurrence (LR) of malignant disease of the eye as an alternative to enucleation or other local salvage treatments. METHODS AND MATERIALS: It was performed a retrospective analysis of all patients who underwent REPBT for LR. The main parameters evaluated were local control and progression-free survival, besides the toxicity profile. RESULTS: There were eight patients who underwent REPBT, seven due to uveal melanoma and one due to retinoblastoma. The median time between the first plaque brachytherapy and the salvage plaque brachytherapy was 24 months (8-49 months). After a median followup of 30 months (8-70 months), the actuarial 2-year local control and progression free survival was 87.5% and 60%, respectively. All patients evolved with worsening of the visual acuity and cataract. Other complications observed were maculopathy (two patients) and glaucoma (one patient). CONCLUSIONS: REPBT should be considered as an option for salvage therapy of LR of malignant disease of the eyes as it provides a high probability of tumor control and eye preservation without compromising disease-free survival. PMID- 24231150 TI - Perioperative anaphylactic reactions: Review and procedure protocol in paediatrics. AB - Perioperative anaphylactic reactions are immediate, hypersensitive reactions that are potentially life-threatening resulting from a sudden release of mediators from mast cells and basophiles, due to either immune (IgE or non-IgE mediated) or non-immune mechanisms. The most frequent causing agents are neuromuscular blocking agents (NMBAs), latex and antibiotics, with latex being the first cause in paediatrics. With regard to perioperative anaphylactic reactions, the usual early signs and symptoms of an anaphylactic reaction could be overlooked or erroneously interpreted and non-severe anaphylaxis could go undetected, with a risk of more severe reactions in the future. Using the data registered on the anaesthesia sheet, it is essential to establish a chronological relationship between drugs and/or substances administered and the reaction observed. An elevated level of tryptase confirms an anaphylactic reaction, but this does not usually increase in the absence of compromised circulation. An allergy study should be carried out preferably between 4 and 6 weeks after the reaction, using a combination of specific IgE, skin and controlled exposure tests (if indicated). Test sensitivity is good for NMBAs, latex, antibiotics, chlorhexidine, gelatine and povidone, and poor for barbiturates, opiates (these can give false positives since they are histamine releasers) and benzodiazepines. Special preventive measures should be taken, especially in the case of latex. We present the maximum concentrations recommended for skin tests, the recommended dosage to treat anaphylactic reactions in paediatrics and a procedure algorithm for the allergological study of these reactions. PMID- 24231151 TI - Epstein-Barr virus infection triggering a haemophagocytic syndrome. PMID- 24231152 TI - Regulation of human skin mast cell histamine release by PDE inhibitors. AB - BACKGROUND: Mast cell and basophiles are thought to be central to inflammation that has an allergic basis as allergens activate these cells in an IgE-dependent manner to generate mediators such as histamine, eicosanoids and cytokines. Phosphodiesterase (PDE) is known to exist as multiple molecular forms of enzyme that metabolise the second messengers. Studies of our own have shown that, of a variety of isoform-selective drugs, the PDE4-selective inhibitors, such as rolipram, attenuate the IgE-mediated release of histamine from human basophiles but not from human lung mast cells (HLMC). The main aim of the present study was to characterise the type and role of PDEs regulating human skin mast cells by using selective and non-selective PDE inhibitors. METHODS: Cells were pre-treated for 15 min with these agents and then challenged with an optimal releasing concentration of anti IgE (1:300) for a further 25 min for the release of histamine. RESULTS: The data show that all the selective PDE-inhibitor compounds (10(-5)M) were ineffective whereas the non-selective PDE inhibitor, theophylline (10(-3)M), inhibited histamine release from HSMC (74 +/- 4% inhibition; p<0.05). None of the selective PDE inhibitors had any effect on histamine release from HLMC whereas, in basophiles, compounds with activity at PDE 4 (rolipram, denbufylline, Ro-2017, Org 30029) were effective inhibitors of histamine release. CONCLUSION: The data suggest that unlike most inflammatory cells, PDE-selective inhibitors are ineffective stabilisers of HSMC activity which is similar to HLMC. PMID- 24231153 TI - Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis. AB - BACKGROUND: Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking. METHODS: A literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed. RESULTS: The number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077-0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086-0.182) (Q=13.9; p<0.001). CONCLUSION: Palivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients. PMID- 24231154 TI - Latent Toxoplasma gondii infection leads to improved action control. AB - The parasite Toxoplasma gondii has been found to manipulate the behavior of its secondary hosts to increase its own dissemination which is commonly believed to be to the detriment of the host (manipulation hypothesis). The manipulation correlates with an up-regulation of dopaminergic neurotransmission. In humans, different pathologies have been associated with T. gondii infections but most latently infected humans do not seem to display overt impairments. Since a dopamine plus does not necessarily bear exclusively negative consequences in humans, we investigated potential positive consequences of latent toxoplasmosis (and the presumed boosting of dopaminergic neurotransmission) on human cognition and behavior. For this purpose, we focused on action cascading which has been shown to be modulated by dopamine. Based on behavioral and neurophysiological (EEG) data obtained by means of a stop-change paradigm, we were able to demonstrate that healthy young humans can actually benefit from latent T. gondii infection as regards their performance in this task (as indicated by faster response times and a smaller P3 component). The data shows that a latent infection which is assumed to affect the dopaminergic system can lead to paradoxical improvements of cognitive control processes in humans. PMID- 24231155 TI - Lignocellulosic ethanol production at high-gravity: challenges and perspectives. AB - In brewing and ethanol-based biofuel industries, high-gravity fermentation produces 10-15% (v/v) ethanol, resulting in improved overall productivity, reduced capital cost, and reduced energy input compared to processing at normal gravity. High-gravity technology ensures a successful implementation of cellulose to ethanol conversion as a cost-competitive process. Implementation of such technologies is possible if all process steps can be performed at high biomass concentrations. This review focuses on challenges and technological efforts in processing at high-gravity conditions and how these conditions influence the physiology and metabolism of fermenting microorganisms, the action of enzymes, and other process-related factors. Lignocellulosic materials add challenges compared to implemented processes due to high inhibitors content and the physical properties of these materials at high gravity. PMID- 24231156 TI - Fiber type characterization of striated muscles related to micturition in female rabbits. AB - Pelvic and perineal striated muscles are relevant for reproduction and micturition in female mammals. Damage to these muscles is associated with pelvic organ prolapse and stress urinary incontinence. The fiber type composition of skeletal muscle influences the susceptibility for damage and/or regeneration. The aim of the present study was to determine the fiber type composition of a perineal muscle, the bulbospongiosus, and a pelvic muscle, the pubococcygeus. Both muscles were harvested from adult female rabbits (8-10 months old). NADH-TR (nicotinamide adenine dinucleotide tetrazolium reductase) histochemistry was undertaken to identify oxidative and glycolytic muscle fibers. Alkaline (pH 9.4) ATP-ase (actomyosin adenosine triphosphatase) histochemistry was used to classify type I, type IIb or type IIa/IId muscle fibers. Results showed that the content of glycolytic fibers in the bulbospongiosus muscle was higher than that of oxidative fibers. Meanwhile, the opposite was true for the pubococcygeus. In the bulbospongiosus muscle, the content of type IIb muscle fibers was higher than that of type I, but was similar to that of type IIa/IId. In contrast, the content of each fiber type was similar in the pubococcygeus muscle. The relative proportion of fibers in bulbospongiosus and pubococcygeus muscles is consistent with their function during voiding and storage phases of micturition. PMID- 24231157 TI - All-cause mortality in hospitalized patients with infectious diarrhea: Clostridium difficile versus other enteric pathogens in Austria from 2008 to 2010. AB - BACKGROUND: Clostridium difficile infection is the leading cause of gastroenteritis-associated deaths in the industrialized world, followed by infection with norovirus. METHODS: Using a cohort study design, we compared 90 inpatients with diarrhea due to C. difficile infection (CDI) with 180 inpatients with diarrhea due to other infectious agents (including 55% with norovirus infection) with respect to complications and all-cause mortality. The effects of age, severity of underlying diseases and additional infections were assessed by stratified analyses. RESULTS: Diarrhea recurrence occurred 8.9 (95%CI: 2.9-27.3) times more often in CDI independent of age and severity of comorbidities. The all cause mortality in CDI patients pre-discharge and at 30 and 180 days, respectively, was 20.0%, 17.0% and 42.3% versus 7.2%, 6.7% and 22.5% in non-CDI diarrhea patients. Among those patients with low comorbidities, who were younger than 65 years and without additional infections, the all-cause pre-discharge, 30 day and 180-day mortality risks were significantly higher for the CDI diarrhea patients than the non-CDI diarrhea patients. This association was not observed among patients with an older age, more severe comorbidities or additional infections. CONCLUSION: CDI results in higher all-cause mortality than diarrhea due to other infectious agents in younger patients with low comorbidities. PMID- 24231158 TI - Idiopathic CD4 lymphopenia associated with neuroinvasive West Nile disease: case report and review of the literature. AB - Idiopathic CD4 lymphocytopenia is a very rare condition resulting in an immunodeficiency disorder that may or may not result in opportunistic infections. Since its description in the early 1990s, the reason for this immune deficiency has remained unclear. Its association with viral illnesses, such as West Nile virus infection, has yet to be described. We report a 26-year-old patient who presented with fever, ascending paralysis, and progressive weakness of the upper extremities. To our knowledge, this is the first case of neuroinvasive West Nile virus occurring in the context of a diagnosis of idiopathic CD4 lymphocytopenia. PMID- 24231159 TI - Use of ATP bioluminescence for assessing the cleanliness of hospital surfaces: a review of the published literature (1990-2012). AB - Hospital cleanliness tends to be considered by patients and the public as an important indicator of the general quality of healthcare. Tests for detecting the presence of adenosine triphosphate (ATP) as a proxy of microbial contamination are increasing in popularity, and several studies have been conducted on this topic in the last few decades. The aim of the present study was to review the published literature on this topic and summarize and discuss the available results. The review focused on relevant English-language articles that were identified through searches of two databases [PubMed and Scopus (1990-2012)] by using the keywords "ATP", "bioluminescence", "hospital", and "surfaces". Twelve articles were included and analyzed. ATP measurements showed a wide variation, with values ranging from 0 to >500,000 relative light units (RLU)/s before cleaning and from 3 to 500,000RLU/s after cleaning. ATP benchmarks used by authors ranged from 100 to 500RLU/s. The percentage of surfaces exceeding the chosen cut-off limit showed a failure rate varying from 21.2% to 93.1% before cleaning and from 5.3% to 96.5% after cleaning. Although the use of ATP bioluminescence can be considered a quick and objective method for assessing hospital cleanliness, it appears to be still poorly standardized at both the national and international level. PMID- 24231160 TI - Bacterial community structure and its regulating factors in the intertidal sediment along the Liaodong Bay of Bohai Sea, China. AB - Investigating the entire species composition of the microorganisms is crucial to understand their roles in the biogeochemical cycles. Metagenomic DNA was extracted from six intertidal sediment samples along the Liaodong Bay of Bohai Sea, China, and was sequenced which yielded a total of 64,496 high-quality sequences from 83,485 reads, with an average read length of 463 bp. The sequences were assigned to 20,718 operational taxonomic units (OTUs) which belong to 42 phyla, 90 classes and 376 genera. At the different taxonomic levels, both the dominants and their abundances varied significantly among the six sites. Phylum Proteobacteria predominated in all the six samples, however, not only the abundance of this phylum varied significantly but also the proportions of Alpha-, Beta-, Gamma-, and delta- and epsilon-Proteobacteria varied greatly. The site sediment median grain size and dissolved oxygen (DO) revealed to be key factors regulating the observed significant differences in the bacterial community between sampling sites. In addition, the bacterial composition might be more sensitive than the richness and diversity to the studied environmental conditions. PMID- 24231161 TI - Genomic analysis of three sponge-associated Arthrobacter Antarctic strains, inhibiting the growth of Burkholderia cepacia complex bacteria by synthesizing volatile organic compounds. AB - In this work we analyzed the ability of three Arthrobacter strains (namely TB23, TB26 and CAL618), which were isolated from the Antarctic sponges Haliclonissa verrucosa and Lyssodendrix nobilis, to specifically inhibit the growth of a panel of 40 Burkholderia cepacia complex strains, representing a major cause of infections in patients that are affected by Cystic Fibrosis. The inhibitory activity was due to the synthesis of antimicrobial compounds, very likely volatile organic compounds (VOCs), and was partially dependent on the growth media that were used for Antarctic strains growth. The phylogenetic analysis revealed that two of them (i.e. CAL 618 and TB23) were very close and very likely belonged to the same Arthrobacter species, whereas the strain TB26 was placed in a distant branch. The genome of the strains TB26 and CAL618 was also sequenced and compared with that of the strain TB23. The analysis revealed that TB23 and CAL618 shared more genomic properties (GC content, genome size, number of genes) than with TB26. Since the three strains exhibited very similar inhibition pattern vs Bcc strains, it is quite possible that genes involved in the biosynthesis of antimicrobial compounds very likely belong to the core genome. PMID- 24231162 TI - Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus. AB - Complete and independent tetramycin and nystatin gene clusters containing varying lengths of type I polyketide synthase (PKS) genes were isolated from Streptomyces ahygroscopicus, a producer of tetramycin (a tetraene) in large amounts and nystatin A1 (a heptaene) in small amounts. Tetramycin was similar to pimaricin, and nystatin A1 was similar to amphotericin. All these polyene macrolide antibiotics possessed the same macrolactone ring biosynthesized from coenzyme A precursors by PKSs but had different number of atoms in the macrolactone ring and side groups. Because tetramycin and nystatin shared limited coenzyme A precursors in the same producer organism, blocking the consumption of precursors in tetramycin pathway may increase the coenzyme A pool. Thus, we genetically manipulated the tetramycin PKS to enhance nystatin production. The type I PKS ttmS1 gene mutant abolished production of tetramycin and had a beneficial effect on the production of nystatin A1. For the mutant, the yield of nystatin A1 was increased by 10-fold compared to that of the wild-type. Thus, deletion of the tetramycin pathway redirected precursor metabolic fluxes and provided an easy genetic approach to manipulate organisms and to increase production levels of a precise target. PMID- 24231163 TI - Psychiatric assessment of severe presentations in autism spectrum disorders and intellectual disability. AB - Children with autism spectrum and related disorders and intellectual disability are not protected from the experience of psychiatric illnesses. Many factors can contribute to exacerbation of existing behavioral symptoms or to the emergence of new psychiatric problems. The psychiatric assessment must thus take into account a range of possible etiologic or contributory factors. The approach outlined in this article highlights the value of assessing 4 broad domains, including diagnostic (genetic) factors, medical considerations, developmental influences, and environmental factors. Examples of how the consideration of each of these domains may inform the diagnostic formulation are highlighted. PMID- 24231164 TI - Emotion regulation: concepts & practice in autism spectrum disorder. AB - The purpose of this article is to describe emotion regulation, and how emotion regulation may be compromised in patients with autism spectrum disorder (ASD). This information may be useful for clinicians working with children with ASD who exhibit behavioral problems. Suggestions for practice are provided. PMID- 24231165 TI - Behavioral approaches to managing severe problem behaviors in children with autism spectrum and related developmental disorders: a descriptive analysis. AB - Severe problem behaviors such as aggression, self-injury, and property destruction can result in injury, and require specialized and expensive treatment. This article reviews outcome research published since 1995 that used behavioral techniques to decrease severe problem behaviors among children and adolescents with autism spectrum disorder and/or intellectual disability. Many relatively simple interventions were reported to significantly reduce severe problem behavior, which offers hope for practitioners. Nonetheless, these studies also reveal a risk for injury and a need for specialized assessment and placement, careful tracking, and high-quality treatment that few agencies could likely replicate without increases in training and support. PMID- 24231166 TI - Using communication to reduce challenging behaviors in individuals with autism spectrum disorders and intellectual disability. AB - This article describes the relationship between expressive communication impairments and common challenging behaviors in individuals with Autism Spectrum Disorder and Intellectual Disability. The communication challenges of individuals with Autism Spectrum Disorder/Intellectual Disability are described and several evidence-based intervention strategies are proposed to support communication so as to decrease challenging behaviors. Recommendations for practice are offered. PMID- 24231168 TI - Psychopharmacologic management of serious behavioral disturbance in ASD. AB - Individuals diagnosed with autism spectrum disorders (ASD) often exhibit serious behavioral disturbance (irritability) including severe tantrums, aggression, and self-injury that requires pharmacologic management. Research focused on the treatment of severe irritability has primarily involved the atypical antipsychotics, including risperidone and aripiprazole. Anticonvulsants have also been investigated for targeting serious behavioral disturbance; however findings have been mixed. Advances in the pharmacotherapy of irritability in ASD continue to inform practice. Research is needed to develop safer and more effective drug treatments for serious behavioral disturbance in this population. PMID- 24231167 TI - Examination of aggression and self-injury in children with autism spectrum disorders and serious behavioral problems. AB - This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder (ASD) who participated in 2 risperidone trials. The narratives were derived from a parent interview about each child's 2 most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and nonaggressive. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD. PMID- 24231169 TI - Management of agitation in individuals with autism spectrum disorders in the emergency department. AB - Individuals with autism spectrum disorder (ASD) presenting with acute agitation in emergency departments (ED) during a crisis situation present both diagnostic and treatment challenges for ED personnel, families, caregivers, and patients seeking treatment. This article describes the challenges that individuals with ASD face when receiving treatment in crisis and emergency settings. Additionally, this article provides information for emergency physicians, ED personnel, and crisis response teams on a systematic, minimally restrictive approach when assessing and providing treatment to patients with ASD presenting with acute agitation in ED settings. PMID- 24231170 TI - Systems of care for individuals with autism spectrum disorder and serious behavioral disturbance through the lifespan. AB - Individuals with Autism Spectrum Disorder present with unique characteristics, and the interventions designed to address associated challenging behaviors must be highly individualized to best meet their needs and those of their families. This article reviews systems of care to support the child, adolescent, or adult with Autism Spectrum Disorder and/or Intellectual Disability. The review describes mental health/behavioral health services, Intellectual Disability and other support systems, and the systems involved in a child and adolescent's life and transition to adulthood. The types of systems and services, as well as barriers, are delineated with a brief listing of Web sites and references. PMID- 24231171 TI - Residential treatment of serious behavioral disturbance in autism spectrum disorder and intellectual disability. AB - For children diagnosed with an autism spectrum disorder and/or intellectual disability, the co-occurrence of serious behavioral disturbance can pose significant health and safety risks, impede normal learning and development, and put great stress on family systems. The complexity and seriousness of the clinical concerns often tax the existing service and funding systems. Although residential treatment has been criticized as an outdated and ineffective mode of treatment, newer models of residential treatment that combine specialized comprehensive services, evidence-based interventions, intensive family support and training, and treatment overlap with community providers can offer an effective and efficient treatment option. PMID- 24231172 TI - Psychiatric hospital treatment of children with autism and serious behavioral disturbance. AB - Children with autism spectrum disorder are psychiatrically hospitalized much more frequently than children in the general population. Hospitalization occurs primarily because of externalizing behaviors and is associated with behavioral disturbance, impaired emotion regulation, and psychiatric comorbidity. Additionally, a lack of practitioner and/or administrator training and experience with this population poses risks for denial of care by third-party payers or treatment facilities, inadequate treatment, extended lengths of stay, and poor outcomes. Evidence and best practices for the inpatient psychiatric care of this population are presented. Specialized treatment programs universally rely on multidisciplinary approaches, including behaviorally informed interventions. PMID- 24231173 TI - The family context of autism spectrum disorders: influence on the behavioral phenotype and quality of life. AB - This article reports the findings from a longitudinal program of research examining the bidirectional influences of the family environment on the behavioral phenotype of autism, and describes a newly developed family psychoeducation program, titled Transitioning Together, designed to reduce family stress, address behavior problems, and improve the overall quality of life of adolescents with autism and their families. A case study is presented that illustrates how Transitioning Together helps reduce family stress and improve the overall quality of the family environment. The article concludes with a discussion of directions for future research on best practices in working with families of children, adolescents, and adults with autism. PMID- 24231174 TI - Autism and developmental disorders: management of serious behavioral disturbance. PMID- 24231175 TI - Culture related to road traffic safety: a comparison of eight countries using two conceptualizations of culture. AB - The majority of previous cross-country studies of human factors relevant to traffic safety have not operationalized and measured culture. Also studies in this vein have mostly been carried out in Europe and the United States. The aim of the study was to examine country cluster differences, based on the Culture's Consequences framework, in road traffic risk perception, attitudes towards traffic safety and driver behaviour in samples from Norway, Russia, India, Ghana, Tanzania, Uganda, Turkey and Iran. An additional aim was to examine cluster differences in road traffic culture as symbol use and to investigate whether this theoretical cultural framework predicts risk perception, attitudes towards traffic safety and driver behaviour in the country clusters. The sample consisted of a total of 2418 individuals who were obtained by convenience sampling in the different countries. The countries segmented into four Culture's Consequences clusters; Norway, Russia and India, Sub-Saharan Africa, and Near East countries. The findings showed that Norwegians reported overall safer attitudes towards traffic safety and driver behaviour than the remaining country clusters. Individuals in Africa reported the highest risk perception. The countries also differed substantially in road traffic culture as symbol use. Contrary to established cultural theory, prediction models revealed that cultural factors were stronger predictors of driver behaviour than of risk perception. Also, the social cognitive risk constructs (i.e. risk perception and attitudes) solely explained variance in driver behaviour in the Norwegian and Russia/India clusters. Previous empirical efforts, which aimed to demonstrate that culture is important for the risk perception criterion, may have focused on a criterion variable that is not strongly related to driver behaviour. Furthermore, countermeasures aimed to influence social cognition may have stronger applicability in countries with a more individualistic western cultural orientation. PMID- 24231176 TI - The validity of the session-RPE method for quantifying training load in water polo. AB - CONTEXT: The assessment of internal training load (ITL) using the session rating of perceived exertion (session RPE) has been demonstrated to provide valuable information, also in team sports. Nevertheless, no studies have investigated the use of this method during youth water polo training. PURPOSE: To evaluate youth water polo training, showing the corresponding level of reliability of the session-RPE method. METHODS: Thirteen male youth water polo players (age 15.6 +/- 0.5 y, height 1.80 +/- 0.06 m, body mass 72.7 +/- 7.8 kg) were monitored during 8 training sessions (80 individual training sessions) over 10 d. The Edwards summated heart-rate-zone method was used as a reference measure of ITL; the session-RPE rating was obtained using CR-10 scale modified by Foster. The Pearson product-moment was applied to regress the Edwards heart-rate-zone method against CR-10 session RPE for each training session and individual data. RESULTS: Analyses reported overall high (r = .88, R(2) = .78) and significant (P < .001) correlations between the Edwards heart-rate and session-RPE methods. Significant correlations were also shown for each training session (r range .69-.92, R(2) range .48-.85, P < .05) and individual data (r range .76-.98, R(2) range .58-.97, P < .05). DISCUSSION: The results confirmed that the session-RPE method as an easy and reliable tool to evaluate ITL in youth water polo, allowing coaches to efficiently monitor their training plans. PMID- 24231177 TI - Controlled co-deposition of FePt nanoparticles embedded in MgO: a detailed investigation of structure and electronic and magnetic properties. AB - Films of FePt nanoparticles (NPs) embedded in MgO were obtained by controlled co deposition of FePt NPs pre-formed by a gas aggregation source and of Mg evaporated in an oxygen atmosphere. Assemblies of core-shell FePt@MgO NPs and films of FePt NPs embedded in MgO matrix could be obtained by varying FePt and Mg deposition rates. Transmission electron microscopy (TEM) and high resolution-TEM revealed the core-shell structure of the NPs, with an FePt core (of average diameter (d) = 4.75 nm) presenting a multitwinned icosahedral structure, and MgO partially in crystalline form. The functional effect of the MgO shell in shielding the FePt core from external oxidation was shown with XPS. Upon controlled annealing, a transition from A1 to L10 ordering could be obtained, with structural and morphological re-arrangement. The magnetic hysteresis loops obtained from alternating gradient field magnetometry at room temperature show a 'wasp-waist' shape, with small values of coercive field (Hc = 300-1400 Oe), decreasing at increasing amounts of co-deposited MgO. PMID- 24231179 TI - Should women with HIV, or at high risk of contracting HIV, use progestogen containing contraception? PMID- 24231178 TI - Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts. AB - OBJECTIVE: To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study and Nurses' Health Study II. PARTICIPANTS: 194,711 women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses' Health Study and 1989 in the Nurses' Health Study II and followed up through 2010. MAIN OUTCOME MEASURE: Incident ulcerative colitis and Crohn's disease. RESULTS: During 3,421,972 person years of follow-up, we documented 284 cases of Crohn's disease and 363 cases of ulcerative colitis. The risk of Crohn's disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn's disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn's disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn's disease among women in the highest fifth of physical activity was 8 and 6 events per 100,000 person years compared with 11 and 16 events per 100,000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn's disease (all P for interaction >0.35). CONCLUSION: In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn's disease but not of ulcerative colitis. PMID- 24231180 TI - Longitudinal ultrasound through the testicle. PMID- 24231181 TI - Surgeons say they lack institutional support when things go wrong. PMID- 24231182 TI - WHO warns world over health needs in Philippines. PMID- 24231184 TI - On the causal efficacy of natural selection: A response to Richards' critique of the standard interpretation. AB - Given the amount of literature devoted to the reasoning used in Darwin's Origin of Species, an interpretation seeking to revise the standard take on Darwin's methodology is unexpected. Yet, Richards (1997, 1998, 2005) challenges the view that Darwin drew an analogy in the Origin on the grounds that such a strategy could not support the possibility of a new species emerging. I suggest, however, that how one interprets causal efficacy is intimately connected with Darwin's use of analogy. A more robust conception of natural selection, as found in the Origin, supports the standard interpretation, significantly weakening Richards' charge of a paradox. PMID- 24231183 TI - Expressed IgH MU and tau transcripts share diversity segment in ranched Thunnus orientalis. AB - It is now appreciated that in addition to the immunoglobulin (Ig)M and D isotypes fish also make the mucosal IgT. In this study we sequenced the full length of Ig tau as well as MU in the commercially important Thunnus orientalis (Pacific bluefin tuna), the first molecular analysis of these two Ig isotypes in a member of the order Perciformes. Tuna IgM and IgT are each composed of four constant (CH) domains. We cloned and sequenced 48 different variable (VH) domain gene rearrangements of tuna immunoglobulins and grouped the VH gene sequences to four VH gene segment families based on 70% nucleotide identity. Three VH gene families were used by both IgM and IgT but one group was only found to be used by IgM. Most interestingly, both MU and tau clones appear to use the same diversity (DH) segment, unlike what has been described in other species, although they have dedicated IgT and IgM joining (JH) gene segments. We complemented this repertoire study with phylogenetic and tissue expression analysis. In addition to supporting the development of humoral vaccines in this important aquaculture species, these data suggest that the DH-JH recombination rather than the VH-DH recombination may be instructive for IgT versus IgM/D bearing lymphocyte lineages in some fish. PMID- 24231185 TI - Disciplining and popularizing: evolution and its publics from the modern synthesis to the present. AB - This paper serves as an introduction to a special collection of papers exploring the centrifugal and centripetal forces in the process of disciplining and popularizing the science of evolution in the period preceding and after the modern synthesis of evolution. PMID- 24231187 TI - Retrospective studies: excellent tools to complement surveillance. PMID- 24231186 TI - The first identification and retrospective study of Severe Fever with Thrombocytopenia Syndrome in Japan. AB - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. METHODS: Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. RESULTS: A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged >=50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. CONCLUSIONS: SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country. PMID- 24231188 TI - Evaluating temperature and duration in arterial tissue fusion to maximize bond strength. AB - Tissue fusion is a growing area of medical research that enables mechanical closure of tissues without the need of foreign bodies such as sutures or staples. Utilizing heat and pressure applied for a specified time, a bond can be formed between adjacent tissues. The success or failure of tissue fusion is contingent upon the strength of the bond it creates between opposing tissues, yet little characterization has been done to measure the strength of this interface as a function of the input parameters, such as heat and pressure. Previous studies have examined the strength of tissue fusion using clinically relevant outcomes such as bursting pressure or tearing strength, but none have explored metrics more appropriate for determining the mechanics of the actual bond such as peel or shear strengths. The goal of this study is to establish methodology for T-peel and lap shear testing of fused tissues and measure the fusion bonding strength as a function of temperature and time using the ConMed Altrus((r)) laparoscopic thermal fusion device. Across five temperatures (120, 140, 150, 160, 170 degrees C) and four time durations (500, 1000, 1800, 3000ms) the mean peeling strength, ultimate shear strength, and bursting pressure of fused porcine splenic arteries were measured. The shear strength increased with increasing temperature and time with an ultimate shear strength at 160 degrees C and 3000ms equal to 290 +/- 99Pa. No trend was observed between the input parameters of time and applied temperature and the mean peeling force, although there were significant differences between groups. The bursting pressure increased significantly with increasing durations, but no trend was noted between temperature and bursting pressure. The shear strength data suggest there is some physical or chemical reaction which occurs in the tissue between 120 degrees C and 150 degrees C which provides a stronger bond. The shear and peel results also reveal that the fusion bond undergoes brittle failure. This study suggests that the tissue fusion bond is maximized at temperatures over 150 degrees C and at a time of 3000ms using the ConMed Altrus((r)) and that input parameters can be tuned to optimize the strength of the bonded region. PMID- 24231189 TI - Highly resolved strain imaging during needle insertion: Results with a novel biologically inspired device. AB - Percutaneous needle insertions are a common part of minimally invasive surgery. However, the insertion process is necessarily disruptive to the substrate. Negative side effects are migration of deep-seated targets and trauma to the surrounding material. Mitigation of these effects is highly desirable, but relies on a detailed understanding of the needle-tissue interactions, which are difficult to capture at a sufficiently high resolution. Here, an adapted Digital Image Correlation (DIC) technique is used to quantify mechanical behaviour at the sliding interface, with resolution of measurement points which is better than 0.5mm, representing a marked improvement over the state of the art. A method for converting the Eulerian description of DIC output to Lagrangian displacements and strains is presented and the method is validated during the simple insertion of a symmetrical needle into a gelatine tissue phantom. The needle is comprised of four axially interlocked quadrants, each with a bevel tip. Tests are performed where the segments are inserted into the phantom simultaneously, or in a cyclic sequence taking inspiration from the unique insertion strategy associated to the ovipositor of certain wasps. Data from around the needle-tissue interface includes local strain variations, material dragged along the needle surface and relaxation of the phantom, which show that the cyclic actuation of individual needle segments is potentially able to mitigate tissue strain and could be used to reduce target migration. PMID- 24231190 TI - Uncertainty analysis of multi-rate kinetics of uranium desorption from sediments. AB - Multi-rate surface complexation models have been proposed to describe the kinetics of uranyl (U(VI)) surface complexation reactions (SCR) rate-limited by diffusive mass transfer to and from intragranular sorption sites in subsurface sediments. In this study, a Bayesian-based, Differential Evolution Markov Chain method was used to assess the uncertainty and to identify factors controlling the uncertainties of the multi-rate SCR model. The rate constants in the multi-rate SCR were estimated with and without assumption of a specified lognormal distribution to test the lognormal assumption typically used to minimize the number of the rate constants in the multi-rate model. U(VI) desorption under variable chemical conditions from a contaminated sediment at US Hanford 300 Area, Washington was used as an example. The results indicated that the estimated rate constants without a specified lognormal assumption approximately followed a lognormal distribution, indicating that the lognormal is an effective assumption for the rate constants in the multi-rate SCR model. However, those rate constants with their corresponding half-lives longer than the experimental durations for model characterization had larger uncertainties and could not be reliably estimated. The uncertainty analysis revealed that the time-scale of the experiments for calibrating the multi-rate SCR model, the assumption for the rate constant distribution, the geochemical conditions involved in predicting U(VI) desorption, and equilibrium U(VI) speciation reaction constants were the major factors contributing to the extrapolation uncertainties of the multi-rate SCR model. Overall, the results from this study demonstrated that the multi-rate SCR model with a lognormal distribution of its rate constants is an effective approach for describing rate-limited U(VI) desorption; however, the model contains uncertainties, especially for those smaller rate constants, that require careful consideration for predicting U(VI) sorption and desorption. PMID- 24231191 TI - Increased expression and copy number amplification of LINE-1 and SINE B1 retrotransposable elements in murine mammary carcinoma progression. AB - In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons and endogenous retroviruses represent large families of repeated elements encoding reverse transcriptase (RT) proteins. Short Interspersed Nuclear Element B1 (SINE B1) retrotrasposons do not encode RT, but use LINE-1-derived RT for their retrotransposition. We previously showed that many cancer types have an abundant endogenous RT activity. Inhibition of that activity, by either RNA interference-dependent silencing of active LINE-1 elements or by RT inhibitory drugs, reduced proliferation and promoted differentiation in cancer cells, indicating that LINE-1-encoded RT is required for tumor progression. Using MMTV PyVT transgenic mice as a well-defined model of breast cancer progression, we now report that both LINE-1 and SINE B1 retrotransposons are up-regulated at a very early stage of tumorigenesis; LINE-1-encoded RT product and enzymatic activity were detected in tumor tissues as early as stage 1, preceding the widespread appearance of histological alterations and specific cancer markers, and further increased in later progression stages, while neither was present in non pathological breast tissues. Importantly, both LINE-1 and SINE B1 retrotransposon families undergo copy number amplification during tumor progression. These findings therefore indicate that RT activity is distinctive of breast cancer cells and that, furthermore, LINE-1 and SINE B1 undergo copy number amplification during cancer progression. PMID- 24231192 TI - Ferritin heavy chain as main mediator of preventive effect of metformin against mitochondrial damage induced by doxorubicin in cardiomyocytes. AB - The efficacy of doxorubicin (DOX) as an antitumor agent is greatly limited by the induction of cardiomyopathy, which results from mitochondrial dysfunction and iron-catalyzed oxidative stress in the cardiomyocyte. Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein. This study aimed to assess the involvement of FHC as a pivotal molecule in the mitochondrial protection offered by MET against DOX cardiotoxicity. The addition of DOX to adult mouse cardiomyocytes (HL-1 cell line) increased the cytosolic and mitochondrial free iron pools in a time dependent manner. Simultaneously, DOX inhibited complex I activity and ATP generation and induced the loss of mitochondrial membrane potential. The mitochondrial dysfunction induced by DOX was associated with the release of cytochrome c to the cytosol, the activation of caspase 3, and DNA fragmentation. The loss of iron homeostasis, mitochondrial dysfunction, and apoptosis induced by DOX were prevented by treatment with MET 24h before the addition of DOX. The involvement of FHC and NF-kappaB was determined through siRNA-mediated knockdown. Interestingly, the presilencing of FHC or NF-kappaB with specific siRNAs blocked the protective effect induced by MET against DOX cardiotoxicity. These findings were confirmed in isolated primary neonatal rat cardiomyocytes. In conclusion, these results deepen our knowledge of the protective action of MET against DOX induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis. PMID- 24231193 TI - Black box warning: is ketorolac safe for use after cardiac surgery? AB - OBJECTIVE: In 2005, after the identification of cardiovascular safety concerns with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), the FDA issued a black box warning recommending against the use of NSAIDs following cardiac surgery. The goal of this study was to assess the postoperative safety of ketorolac, an intravenously administered NSAID, after cardiac surgery. DESIGN: Retrospective observational study. SETTING: Single center, regional hospital. PARTICIPANTS: A total of 1,309 cardiac surgical patients (78.1% coronary bypass, 28.0% valve) treated between 2006 and 2012. INTERVENTIONS: A total of 488 of these patients received ketorolac for postoperative analgesia within 72 hours of surgery. MEASUREMENT AND MAIN RESULTS: Ketorolac-treated patients were younger, had better preoperative renal function, and underwent less complex operations compared with non-ketorolac patients. Ketorolac was administered, on average, 8.7 hours after surgery (mean doses: 3.1). Postoperative outcomes for ketorolac treated patients were similar to those expected using Society of Thoracic Surgery database risk-adjusted outcomes. In unadjusted analysis, patients who received ketorolac had similar or better postoperative outcomes compared with patients who did not receive ketorolac, including gastrointestinal bleeding (1.2% v 1.3%; p = 1.0), renal failure requiring dialysis (0.4% v 3.0%; p = 0.001), perioperative myocardial infarction (1.0% v 0.6%; p = 0.51), stroke or transient ischemic attack (1.0% v 1.7%; p = 0.47), and death (0.4% v 5.8%; p<0.0001). With adjustment in a multivariate model, treatment with ketorolac was not a predictor for adverse outcome in this cohort (odds ratio: 0.72; p = 0.23). CONCLUSIONS: Ketorolac appears to be well-tolerated for use when administered selectively after cardiac surgery. Although a black box warning exists, the data highlights the need for further research regarding its perioperative administration. PMID- 24231194 TI - Perioperative applications of deformation (myocardial strain) imaging with speckle-tracking echocardiography. PMID- 24231195 TI - Tricuspid valve: an intraoperative echocardiographic perspective. PMID- 24231196 TI - High-fidelity simulation of lung isolation with double-lumen endotracheal tubes and bronchial blockers in anesthesiology resident training. AB - OBJECTIVES: Demonstrate the feasibility of using the AirSim Bronchi airway simulator to teach residents how to manage lung isolation with double-lumen endotracheal tubes and bronchial blockers and evaluate their performance with a detailed checklist. DESIGN: Prospective observational study. SETTING: University anesthesiology residency training program. PARTICIPANTS: Anesthesiology residents taking a cardiothoracic anesthesiology rotation. INTERVENTIONS: Residents were instructed in 7 tasks using the AirSim Bronchi: The use of the fiberoptic bronchoscope, methods for placing left and right double-lumen endotracheal tubes and 3 bronchial blockers (Univent, Arndt, and Cohen), and application of continuous positive airway pressure (CPAP) to the unventilated lung. Two to 3 weeks later, checklists and a detailed scoring system were used to assess performance. Residents rated the curriculum and their own confidence in performing the tasks using a 5-point Likert scale. MEASUREMENTS AND MAIN RESULTS: Thirteen residents completed the curriculum. Their median Likert scale ratings of the curriculum based on a questionnaire with 6 items ranged from 4 to 5 of 5. Resident confidence scores for each lung isolation technique improved after the simulation training, with the median gain ranging from 0.5 to 1.5 Likert levels depending on the task. The largest improvement occurred with the bronchial blockers (p<0.05). The median performance score for the 7 tasks combined was 88% of the maximum possible points. CONCLUSIONS: The authors used the AirSim Bronchi simulator in a novel simulation curriculum to teach lung-isolation techniques to anesthesiology residents and evaluated performance using a detailed checklist scoring system. This curriculum is a promising educational tool. PMID- 24231197 TI - Disconnection technique with a bronchial blocker for improving lung deflation: a comparison with a double-lumen tube and bronchial blocker without disconnection. AB - OBJECTIVE: One-lung ventilation (OLV) is accomplished with a double-lumen tube (DLT) or a bronchial blocker (BB). The authors compared the effectiveness of lung collapse using DLT, BB, and BB with the disconnection technique. DESIGN: Prospective, randomized, blind trial. SETTING: A university hospital. PARTICIPANTS: Fifty-two patients undergoing elective pneumothorax surgery. INTERVENTIONS: Patients were assigned randomly to 1 of 3 groups: The DLT group (group 1), the BB group (group 2), and the BB with the disconnection technique group (group 3). The authors modified the disconnection technique in group 3 as follows: (1) turned off the ventilator and opened the adjustable pressure limiting valve, allowing both lungs to collapse and (2) after loss of the CO2 trace on the capnograph, inflated the blocker cuff and turned on the ventilator, allowing only dependent-lung ventilation. MEASUREMENTS AND MAIN RESULTS: Five and ten minutes after OLV, the degree of lung collapse was assessed by the surgeon, who was blinded to the isolation technique. The quality of lung collapse at 5 and 10 minutes was significantly better in groups 1 and 3 than in group 2. No significant differences were observed for the degree of lung collapse at any time point between groups 1 and 3. The average time for loss of the CO2 trace on the capnograph was 32.3+/-7.0 seconds in group 3. CONCLUSIONS: A BB with spontaneous collapse took longer to deflate and did not provide equivalent surgical exposure to the DLT. The disconnection technique could be helpful to accelerate lung collapse with a BB. PMID- 24231198 TI - Development and validation of a motor function classification in patients with neuromuscular disease: the NM-score. AB - OBJECTIVE: To develop a classification for neuromuscular disease patients in each of the three motor function domains (D1: standing and transfers; D2: axial and proximal function; D3: distal function). MATERIALS AND METHODS: A draft classification was developed by a study group and then improved by qualitative validation studies (according to the Delphi method) and quantitative validation studies (content validity, criterion validity and inter-rater reliability). A total of 448 patients with genetic neuromuscular diseases participated in the studies. RESULTS: On average, it took 6.3minutes to rate a patient. The inter rater agreement was good when the classification was based on patient observation or an interview with the patient (Cohen's kappa=0.770, 0.690 and 0.642 for NM Score D1, D2 and D3 domains, respectively). Stronger correlations (according to Spearman's coefficient) with the respective "gold standard" classifications were found for NM-Score D1 (0.86 vs. the Vignos Scale and -0.88 vs. the Motor Function Measure [MFM]-D1) and NM-Score D2 (-0.7 vs. the Brooke Scale and 0.64 vs. MFM D2) than for NM-Score D3 (0.49 vs. the Brooke scale and -0.49 vs. MFM D3). DISCUSSION/CONCLUSIONS: The NM-Score is a reliable, reproducible outcome measure with value in clinical practice and in clinical research for the description of patients and the constitution of uniform patient groups (in terms of motor function). PMID- 24231199 TI - Long-term reproductive performance after surgery for ovarian endometrioma. AB - OBJECTIVE: To determine the long-term impact of different types of endometrioma surgery on reproductive performance and on age of menopause. STUDY DESIGN: This was a longitudinal observational cohort study of 68 women with previous endometrioma surgery and 68 age- and weight-matched healthy controls. All participants' hospital records were reviewed and each woman completed a questionnaire and attended an interview. Pregnancy rates were compared between the study and control groups. In the study group, pregnancy rates were compared before and after surgery. RESULTS: Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow up period. This was not significantly different from a pre-operative pregnancy rate of 48% (22/46). Of these 19 patients, four achieved another pregnancy with fertility treatment. An additional eight patients conceived only with the help of fertility treatment, giving an overall long-term post-operative pregnancy rate of 71% (27/38). These results were significantly lower (p=0.0001) than the 98% (57/58) long-term natural pregnancy rate in the control group. Pregnancy rates in patients receiving fertility treatment significantly (p=0.001) increased from 7% (1/15) before surgery to 63% (12/19) post-operatively. In post-menopausal women, the median (quartile) age at menopause was similar in the study (n=9) and control groups (n=6) [48 (45-52) versus 49 (44-52) years, respectively]. CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment. PMID- 24231201 TI - Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological deficits and the defining symptoms of ADHD seems more complex than originally thought. Methylphenidate (MPH) is an effective treatment for ADHD symptoms, but its impact on cognition is less clearly understood. METHODS: With a common systematic search strategy and a rigorous coding and data extraction strategy across domains, we searched electronic databases to identify published placebo controlled trials that compared MPH and placebo on executive and nonexecutive memory, reaction time, reaction time variability and response inhibition in children and adolescents (5-18 years) with a formal diagnosis of ADHD. RESULTS: Sixty studies were included in the review, of which 36 contained sufficient data for meta-analysis. Methylphenidate was superior to placebo in all five meta-analyses: executive memory, standardized mean difference (SMD) .26, 95% confidence interval (CI): -.39 to -.13; non-executive memory, SMD .60, 95% CI: .79 to -.41; reaction time, SMD .24, 95% CI: -.33 to -.15; reaction time variability, SMD .62, 95% CI: -.90 to -.34; response inhibition, SMD .41, 95% CI: -.55 to -.27. CONCLUSIONS: These data support the potentially important effects of MPH on various aspects of cognition known to be associated with ADHD. Consideration should be given to adding cognitive outcomes to the assessment of treatment outcome in ADHD, considering the complexity of the relationship between ADHD symptoms and cognition. PMID- 24231200 TI - Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats. AB - BACKGROUND: Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development, are a significant risk factor for later life anxiety disorders such as posttraumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD, such as enhanced fear and anxiety. Here, we used a fear conditioning procedure in juvenile rats before maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD-related symptoms. METHODS: Nineteen-day old rats were exposed to unpredictable and inescapable footshocks, and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning or elevated plus maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid and neuropeptide Y receptors. RESULTS: Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear-related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar glucocorticoid receptors, decreased time spent in the open arm of an elevated plus maze, and an odor aversion associated with early-life footshocks. CONCLUSIONS: These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD, even if there is no explicit memory of the early trauma. PMID- 24231202 TI - OnabotulinumtoxinA office treatment for neurogenic bladder incontinence in Parkinson's disease. AB - OBJECTIVE: To evaluate safety and effectiveness of low-dose (100 U) onabotulinumtoxinA (onabotA) bladder injections as an office procedure with topical anesthesia only for patients with Parkinson's disease (PD) and incontinence. METHODS: Qualified patients who failed oral antimuscarinic agents participated in an open-label study. They discontinued antimuscarinics, provided a King's Health Questionnaire (KHQ), voiding symptom score, and 3-day voiding diary. Free uroflowmetry with post-void ultrasounds and cystometrogram pressure/flow studies were performed. Patients underwent flexible cystoscopy and injections of onabotA 100 U (10 U/mL) dispersed into 10-20 submucosal/detrusor sites of the bladder, including the trigone. Voiding diaries, questionnaires, and free uroflowmetry with post-void ultrasound residual urine measurements were repeated after 1, 3, and 6 months. RESULTS: Twelve men and 8 women were treated: mean age, 70.4 years; duration of disease, 10.6 years; median bladder contraction volume, 115 mL; maximum bladder pressure, 62 cm; and post-void volume, 9 mL. Moderate to marked symptom relief at 3 months and a 50% incontinence decrease over 6 months relative to pretreatment was reported in 59% patients (P <=.02); 5 patients failed to complete the 6-month endpoint. No urinary retention required catheterization. CONCLUSION: Office cystoscopy with low-dose onabotA injection treatment is a potential long-term management strategy for patients with PD and urinary incontinence who fail oral antimuscarinic agents. The treatment seems to be safely utilized for older men with BPH as well as women with potential hypoactive detrusor function. PMID- 24231203 TI - SIU/ICUD Consultation on Urethral Strictures: Urethral strictures in children. AB - A literature search was made through PubMed from 1990 to the present for articles on strictures in children. There were 32 articles that provided the data for this review. The studies were rated according to the level of evidence and the grade of recommendation using the International Consultations in Urologic Disease standards. PMID- 24231204 TI - BAY 41-2272, a soluble guanylate cyclase stimulator, relaxes isolated human ureter in a standardized in vitro model. AB - OBJECTIVE: To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. MATERIALS AND METHODS: Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 +/- 3.2 years, male/female ratio 2:1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. RESULTS: Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 MUM) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 +/- 0.14 and 84% +/- 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 +/- 0.10, P <.05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. CONCLUSION: BAY 41 2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved. PMID- 24231205 TI - Editorial comment. PMID- 24231206 TI - The difficult ureter: stent and come back or balloon dilate and proceed with ureteroscopy? What does the evidence say? PMID- 24231207 TI - Editorial comment. PMID- 24231209 TI - Editorial comment. PMID- 24231210 TI - Trends in the utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer: results from the National Cancer Database. AB - OBJECTIVE: To evaluate variation in neoadjuvant chemotherapy (NAC) use among patients with >= clinical T2 (cT2) bladder cancer and determine changes in staging at radical cystectomy (RC) associated with therapy. METHODS: Using the National Cancer Database (NCDB), we identified all patients diagnosed with organ confined, muscle-invasive (cT2+) urothelial carcinoma of the bladder between 2006 and 2010 who underwent RC. Univariate and multivariate analyses were performed examining demographic, clinical, and hospital factors influencing the delivery of NAC. These included age, gender, race, income, geographic location, type of treating hospital, clinical stage, and patient comorbidities. RESULTS: A total of 5692 patients met our inclusion criteria, 962 (16.9%) of whom received NAC. A multivariable logistic regression model revealed several factors that negatively influenced receipt of NAC: increasing age, lower patient income, and treatment at a nonacademic institution (P <.01). Higher clinical stage and fewer comorbid conditions were associated with higher likelihood of receiving NAC (P <.01). The overall use of NAC increased from 7.6% in 2006 to 20.9% in 2010 (P <.01). Those receiving NAC were significantly more likely to be downstaged at RC (31.2% vs 7.6%, P <.01), with 10.6% achieving complete pathologic downstaging. CONCLUSION: Although the use of NAC for organ-confined muscle invasive bladder cancer remains low, it is increasing over time. Patients receiving NAC are more likely to be downstaged and achieve complete pathologic downstaging. However, there is considerable variation in treatment patterns based on both clinical and nonclinical factors. PMID- 24231211 TI - Prolonged urinary leakage after partial nephrectomy: a novel management pathway. AB - INTRODUCTION: To describe an original method for managing prolonged urinary leakage after partial nephrectomy. We placed a Malecot catheter in the ureter to improve the urinary drainage and therefore avoid the renal percutaneous treatment of the fistula or potential open surgery. TECHNICAL CONSIDERATIONS: We performed ureteral stenting using a 16 F Malecot catheter in 3 patients who had a prolonged urinary fistula after partial nephrectomy in which the placement of a ureteral stent could not resolve the urine leak. Drainage using 2 ureteral catheters was performed, which proved to be insufficient for the urinary fistula to resolve. We subsequently placed in the dilated ureter a 16 F Malecot catheter into the renal pelvis using a cystoscopic approach and a bladder catheter to complete the drainage. In all cases, the urine leak stopped after stenting with the Malecot catheter. At 1 month after the stenting, computed tomography and magnetic resonance imaging showed complete healing of the fistula. No infection or secondary ureteral stricture was reported. CONCLUSION: This technique with a low complication profile can be used as an additional endoscopic step, before more invasive procedures. PMID- 24231212 TI - Possible function of urinary pH and citrate on the ceftriaxone-induced nephrolithiasis. AB - OBJECTIVE: To test whether urinary pH and citrate is associated with ceftriaxone induced kidney stone formation and if acidified urine could dissolve this kind of stone using an in vitro crystallization model. METHODS: Crystallization was induced by mixing ceftriaxone at the standard therapeutic urinary concentration to artificial urine. The response of different physiological pH and citrate on ceftriaxone-induced crystallization was measured by the depletion ratio of ceftriaxone in the process. Compositions of formed crystals were qualitatively and quantitatively analyzed. The effect of acidifying urine on dissolving of ceftriaxone-induced crystal was determined by the surplus ratio of ceftriaxone in the process. RESULTS: Compositional analysis showed that ceftriaxone-induced crystals were composed of calcium and ceftriaxone with a ratio of 1:1. Compared to the response to pH 6.0, ceftriaxone-induced crystallizations in artificial urine at pH 4.5 and 5.0 for 4 hours were significantly decreased, and more acid urine resulted in less crystallization. However, it made no significant change when pH increased to 6.5 and 7.0. In addition, ceftriaxone-induced crystals formed at pH 6.0 for 4 hours could be dissolved significantly when artificial urine was acidified to pH 5.0 and 4.5 for 1, 2, and 4 hours; and more time of dissolution and more degree of acidifying resulted in more dissolution. CONCLUSION: Our study suggests that urinary pH and citrate are probable factors associated with ceftriaxone-induced nephrolithiasis. On one hand, alkaline urine and hypocitraturia predispose ceftriaxone nephrolithiasis, and vice versa. On the other hand, acidifying urine could dissolve ceftriaxone-induced stones. PMID- 24231214 TI - Flexible ureteroscopy with a ureteral access sheath: when to stent? AB - OBJECTIVE: To compare intra- and postoperative data of patients who underwent ureterorenoscopy (URS) with an access sheath, with and without postoperative stenting. METHODS: We retrospectively identified patients who underwent flexible URS with a ureteral access sheath between January 2102 and January 2013. Two surgeons performed all cases; one who routinely stents after flexible ureteroscopy and a second who selectively stents. Fifty-one patients who were stented and 51 patients not stented after URS were enrolled in this study. Patients were matched by operative time as a surrogate measure of complexity of the procedure. Intra- and postoperative data were compared. We also analyzed if preoperative stenting or sheath diameter had any effect on postoperative pain score for each group. RESULTS: Patients in the stented group were older (P <.001), had larger ureteral access sheaths (P <.001), and greater stone burden (P <.001). Despite this, the stented group had lower pain scores (4.5 +/- 3.2 vs 8.9 +/- 3.2; P = .025) and were less likely to seek medical assistance for pain than the unstented patients (26.3% vs 3.9%; P = .007). Patients who were prestented before ureteroscopy had lower pain scores than those who were not prestented in the group that did not receive a postoperative stent (4.2 +/- 3.4 vs 6.6 +/- 2.8; P = .047). CONCLUSION: Postoperative stenting after flexible URS with a ureteral access sheath seems to decrease postoperative pain. Patients might be selected for no ureteral stent if they were prestented before the procedure, and the URS was uneventful. PMID- 24231215 TI - Translabial ultrasonography for evaluation of synthetic mesh in the vagina. AB - OBJECTIVE: To compare the clinical and surgical findings using translabial ultrasonography (US) in the evaluation of symptoms after transvaginal synthetic mesh placement. METHODS: From 2009 through 2010, a retrospective observational study was conducted to evaluate patients presenting with complaints after transvaginal mesh implantation for the treatment of stress urinary incontinence or pelvic organ prolapse repair. The clinical and translabial US findings were compared with the intraoperative findings, with a focus on mesh location, erosion, and extrusion. RESULTS: A total of 51 consecutive patients (mean age 59 years) were evaluated by history and physical examination, translabial US, and intraoperative findings. Using intraoperative findings as the reference standard, translabial US was able to predict the location of the sling in relationship to the urethra (6 distal, 25 mid-urethral, and 20 at the bladder neck), to differentiate between transobturator (n = 21) and retropubic (n = 30) slings, and to detect all anterior (n = 21) and posterior (n = 15) placed mesh. Translabial US was superior to physical examination in identifying mesh erosion into the periurethral fascia or sphincteric unit. US was inferior to physical examination in diagnosing vaginal extrusion but was superior for locating the mesh. CONCLUSION: Translabial US can identify the mesh material used to treat stress urinary incontinence and pelvic organ prolapse. It provides additional information on sling type, mesh location, and morphology compared with the clinical findings and could help in surgical planning and counseling. Prospective clinical studies evaluating the reliability of this technique in larger patient populations are warranted. PMID- 24231216 TI - The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome. AB - OBJECTIVE: To evaluate the efficacy and safety of duloxetine hydrochloride in the treatment of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Thirty-eight CP/CPPS patients completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-Erectile Function-5 (IIEF-5) questionnaires, uroflowmetry, and evaluation of psychologic status using Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). Patients were randomly assigned to 2 treatments groups. Treatment in group 1 consisted of a simultaneous oral administration of tamsulosin (0.4 mg/d, 60 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d). Treatment in group 2 consisted of tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). NIH-CPSI and IIEF-5 questionnaires, uroflowmetry, and evaluation of the psychological status were repeated at 16 weeks of follow-up. RESULTS: At 16 weeks, a significant improvement in NIH-CPSI pain subscore, NIH-CPSI quality of life subscore, and NIH CPSI total score were observed in group 1 patients compared with those in group 2 (P <.01, respectively), together with a significant improvement in HAM-A and HAM D scores (P <.01, respectively). Patients in group 2 showed a significant improvement in NIH-CPSI total score, in the urinary symptoms subscore, and in the HAM-A total score. No significant differences were observed in IIEF-5 scores in the 2 groups. Maximum flow rate significantly increased in both groups. In group 1, 20% of patients stopped the study due to adverse effects. CONCLUSION: The use of duloxetine in a multimodal treatment with an alpha-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychologic status and quality of life patients affected by CP/CPPS. PMID- 24231217 TI - Efficacy of holmium laser enucleation of the prostate in patients with non neurogenic impaired bladder contractility: results of a prospective trial. AB - OBJECTIVE: To examine the outcomes of men with detrusor underactivity or acontractility undergoing holmium laser enucleation of the prostate (HoLEP). METHODS: A prospective case series between 2009 and 2012 was performed to examine short-term outcomes of men with urodynamic evidence of detrusor hypocontractility or acontractility because of a non-neurogenic etiology and concurrent benign prostatic obstruction (BPO), undergoing HoLEP. RESULTS: Fourteen patients with detrusor hypocontractility and 19 patients with acontractility and evidence of BPO underwent HoLEP during the study period. Median age was 71.5 and 75 years, respectively. Preoperatively, 5 (35.7%) men with hypocontractility and 19 (100%) men with acontractility had catheter-dependent urinary retention for a median of 3 and 9 months, respectively. At a median follow-up of 24.7 months, all 5 (100%) men with hypocontractility and 18 of 19 (94.7%) men with acontractility were voiding spontaneously without the need for intermittent catheterization. Individuals with hypocontratile bladders had statistically significant improvements in American Urological Association Symptom Index (21.5 vs 3; P = .014), maximum urine flow (Qmax, 10 vs 21 mL/s; P = .001), and postvoid residual (250 vs 53 mL; P = .007) from baseline to postoperative assessments. In patients with an acontractile bladder, 15 of 19 (78.9%) displayed significant return of detrusor contractility, whereas 4 of 19 (21.1%) were voiding exclusively by Valsalva effort on follow-up urodynamic study. Postoperatively, patient satisfaction, as ascertained by American Urological Association Symptom Index, was high for both groups. CONCLUSION: Intermediate follow-up results indicate that HoLEP is a viable management option for men with BPO and detrusor hypocontractility. Furthermore, detrusor acontractility does not appear to adversely affect postoperative results, with return of spontaneous urination and demonstration of detrusor contractility allowing for efficient voiding, in over 95% of patients. PMID- 24231218 TI - A 60-year-old man with gross hematuria and flank pain. PMID- 24231219 TI - Mucinous neoplasm arising in a urachal cyst: a first in the pediatric population. AB - Urachal anomalies are relatively uncommon and result because of incomplete obliteration of the urachus prenatally. In children, urachal cysts and sinuses constitute the common presentations, and these can sometimes become secondarily infected. Malignant involvement of the urachus in the pediatric population is rare, and primary urachal adenocarcinoma is reported exclusively in adults. Herein, we present the case of an adolescent girl with a low-grade mucinous neoplasm arising in a urachal cyst and discuss its significance. PMID- 24231220 TI - Modified abdominoplasty for patients with the Prune Belly syndrome. AB - OBJECTIVE: To present the results of a new technique for abdominoplasty in patients with the Prune Belly syndrome (PBS). METHODS: Since 1985, 46 children with PBS underwent surgical treatment that included urinary tract reconstruction (UTR), orchidopexy, and abdominoplasty. In 41 patients, we performed the abdominoplasty as follows: (1) fusiform longitudinal resection of the mid abdominal skin and subcutaneous tissue, with preservation of the musculo aponeurotic fascia (MAF) and umbilicus, (2) ellipsoid unilateral longitudinal incision of the MAF in the most weakened side of the abdomen, producing 2 flaps, with the umbilicus being kept intact in the widest flap, (3) after UTR and bilateral orchiopexy, suture fixation of the widest MAF layer to the inner side of the contralateral abdominal wall, creating an inner MAF layer, (4) lateral suture fixation of the other flap over the inner layer, creating an outer MAF layer with a buttonhole exposing the umbilicus, that is sutured to the outer layer, and (5) approximation of the skin edges with incorporation of the umbilicus in the suture. RESULTS: Skin coaptation was excellent in all patients, and no trimming was necessary in incision extremities. There was no dehiscence or skin necrosis and all patients presented immediate improvement of the abdominal tonus and appearance. Further improvement with growth was observed in all except 4 patients, 2 requiring secondary abdominoplasties. CONCLUSION: We conclude that this technique is applicable in all forms of weakened abdomen typical of PBS, even in asymmetrical cases, requiring only 1 MAF incision, with good cosmetic and functional results. PMID- 24231221 TI - Adenovirus-induced obstructive uropathy with acute renal failure in an immunodeficient child. AB - Viral infections represent severe complications in immunodeficient patients, associated with significant morbidity and mortality. We report a case of a bone marrow-transplanted adolescent with hemorrhagic cystitis 4 weeks after transplant, associated with renal failure because of obstructive pyelonephritis. Diagnostic workup finally revealed adenovirus infection. A double-J stent was inserted with spontaneous favorable evolution thereafter. Adenovirus infection in an immunocompromised patient can cause hemorrhagic cystitis without specific symptoms and might evolve toward obstructive pyelonephritis because of tubular necrosis. Diagnosis is made by urine culture and/or blood polymerase chain reaction. In case of fatal dissemination, diagnosis might only be revealed on autopsy. PMID- 24231222 TI - Prospective evaluation of a new visual prostate symptom score, the international prostate symptom score, and uroflowmetry in men with urethral stricture disease. AB - OBJECTIVE: To evaluate the correlation between the visual prostate symptom score (VPSS) and the international prostate symptom score (IPSS) and uroflowmetry parameters in men with urethral stricture disease. The VPSS offers a nonverbal, pictographic assessment of lower urinary tract symptoms. METHODS: A total of 100 men followed up with a diagnosis of urethral stricture were evaluated from March 2011 to November 2012 with IPSS, VPSS, uroflowmetry, urethral calibration, and urethrography. Follow-up every 3 months for 3-18 months was available in 78 men for a total of 289 visits. Procedures performed were urethral dilation in 105, internal urethrotomy in 54, and urethroplasty in 8 patients. Statistical analysis was performed with Spearman's rank correlation, Fisher's exact, and Student t tests. RESULTS: The time taken to complete the VPSS vs IPSS was significantly shorter (118 vs 215 seconds at the first and 80 vs 156 seconds at follow-up visits; P <.001). There were significant correlations between the VPSS and IPSS (r = 0.845; P <.001), maximum urinary flow rate (Qmax; r = 0.681; P <.001) and urethral diameter (r = -0.552; P <.001). A combination of VPSS >8 and Qmax <15 mL/s had positive and negative predictive values of 87% and 89%, respectively, for the presence of urethral stricture. CONCLUSION: The VPSS correlates significantly with the IPSS, Qmax, and urethral diameter in men with urethral stricture disease and takes significantly less time to complete. A combination of VPSS >8 and Qmax <15 mL/s can be used to avoid further invasive evaluation during follow-up in men with urethral strictures. PMID- 24231223 TI - Metal enhanced fluorescence in rare earth doped plasmonic core-shell nanoparticles. AB - We theoretically and numerically investigate metal enhanced fluorescence of plasmonic core-shell nanoparticles doped with rare earth (RE) ions. Particle shape and size are engineered to maximize the average enhancement factor (AEF) of the overall doped shell. We show that the highest enhancement (11 in the visible and 7 in the near-infrared) is achieved by tuning either the dipolar or the quadrupolar particle resonance to the rare earth ion's excitation wavelength. Additionally, the calculated AEFs are compared to experimental data reported in the literature, obtained in similar conditions (plasmon mediated enhancement) or when a metal-RE energy transfer mechanism is involved. PMID- 24231224 TI - Association between physical activity and sleep in adults with chronic pain: a momentary, within-person perspective. AB - BACKGROUND: Individuals with chronic pain consider improved sleep to be one of the most important outcomes of treatment. Physical activity has been shown to have beneficial effects on sleep in the general population. Despite these findings, the physical activity-sleep relationship has not been directly examined in a sample of people with chronic pain. OBJECTIVE: This study aimed to examine the association between objective daytime physical activity and subsequent objective sleep for individuals with chronic pain while controlling for pain and psychosocial variables. DESIGN: An observational, prospective, within-person study design was used. METHODS: A clinical sample of 50 adults with chronic pain was recruited. Participation involved completing a demographic questionnaire followed by 5 days of data collection. Over this period, participants wore a triaxial accelerometer to monitor their daytime activity and sleep. Participants also carried a handheld computer that administered a questionnaire measuring pain, mood, catastrophizing, and stress 6 times throughout the day. RESULTS: The results demonstrated that higher fluctuations in daytime activity significantly predicted shorter sleep duration. Furthermore, higher mean daytime activity levels and a greater number of pain sites contributed significantly to the prediction of longer periods of wakefulness at night. LIMITATIONS: The small sample size used in this study limits the generalizability of the findings. Missing data may have led to overestimations or underestimations of effect sizes, and additional factors that may be associated with sleep (eg, medication usage, environmental factors) were not measured. CONCLUSIONS: The results of this study suggest that engagement in high-intensity activity and high fluctuations in activity are associated with poorer sleep at night; hence, activity modulation may be a key treatment strategy to address sleep complaints in individuals with chronic pain. PMID- 24231225 TI - Psychometric properties of 3 functional mobility tests for people with Parkinson disease. AB - BACKGROUND: Standardized outcome measures with high clinical utility are of paramount importance for clinical practice. OBJECTIVE: The purpose of this study was to examine interrater and intrarater reliability, construct validity, discriminant ability, and smallest detectable differences of the sit-to-stand test (STS), Timed "Up & Go" Test (TUG), and bed mobility test for people with Parkinson disease (PD). DESIGN: A cross-sectional, psychometric evaluation study was conducted. METHODS: A group of individuals with PD (PD group) and a group of individuals who were healthy (control group) were recruited through local PD groups and assessed in a movement laboratory in their "on" phase. Measurements of time to perform one STS, TUG, and bed mobility test were collected based on video recordings of that single performance. RESULTS: Thirty-eight individuals with PD (Hoehn and Yahr stages I-IV) and 19 age-matched control participants were recruited. Intraclass correlation coefficients for interrater and intrarater reliability for the PD group ranged from .95 to .99. Bland-Altman plots showed mean differences close to zero and narrow confidence intervals. Construct validity was established by means of moderate to good Spearman rho correlation coefficients with part III of the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage (range=.51-.63). Timings of all tests discriminated participants in the PD group from those in the control group and participants in the PD group in Hoehn and Yahr stages I and II from those in Hoehn and Yahr stages III and IV but did not discriminate "nonfallers" or those with single falls from repeat "fallers" or "nonfreezers" from "freezers." Applicable smallest detectable differences were established. LIMITATIONS: The results are not generalizable to people in the late stage of PD (Hoehn and Yahr stage IV: n=3). CONCLUSIONS: Timings of video recordings of 3 functional mobility tests with high clinical utility showed good psychometric properties for community-dwelling, ambulatory people with PD. PMID- 24231227 TI - Patient global ratings of change did not adequately reflect change over time: a clinical cohort study. AB - BACKGROUND: Global ratings of change (GROCs) are commonly used in research and clinical practice to determine which patients respond to therapy, but their validity as a criterion for change has not been firmly established. One factor related to their validity is the length of the recall period. OBJECTIVE: The study objective was to examine the influence of the length of the recall period on the validity of a GROC for determining true change over time in the clinical setting. DESIGN: This was a longitudinal, single-cohort observational study. METHODS: Data from the Focus on Therapeutic Outcomes clinical database were collected for 8,955 patients reporting for physical therapy treatment of a knee disorder. Computerized adaptive testing was used to assess knee functional status (FS) at the initial and final (discharge) physical therapy visits. Each patient's GROC was obtained at discharge. Correlation and linear regression analyses of knee FS and GROC, stratified by length of time between intake and discharge, were conducted. RESULTS: Correlations of GROC with knee FS change scores were modest even for the shortest period of recall (0-30 days) and were slightly lower for longer recall periods. Regression analyses using knee FS to predict GROC scores revealed similar findings. Correlations of GROC with intake and discharge scores indicated a strong bias toward discharge status, with little or no influence of baseline status. Standardized regression coefficients fitted the pattern expected for a valid measure of change but confirmed the strong bias toward discharge status. LIMITATIONS: One version of the GROC administered serially in a cohort of patients seen in clinical practice was examined. CONCLUSIONS: These results call into question the validity of GROCs for measuring change over time in routine clinical practice. PMID- 24231226 TI - Declining cognition and falls: role of risky performance of everyday mobility activities. AB - BACKGROUND: Declining cognition is a risk factor for falls among older adults. The extent to which impaired judgment in performance of daily activities increases fall risk is unclear. OBJECTIVE: The aim of this study was to determine whether engagement in mobility activities in a risky manner explains the association between declining cognition and rate of falls. DESIGN: This study was a secondary analysis of baseline and prospective data from older adults enrolled in the intervention arm of a randomized clinical trial. METHODS: Two hundred forty-five community-dwelling older adults (79% female; mean age=79 years, SD=8.0) who were at risk for falls received physical, cognitive, and functional evaluations. Cognition was assessed with the Short Portable Mental Status Questionnaire (SPMSQ). Using interview and in-home assessment data, physical therapists determined whether participants were at risk for falls when performing mobility-related activities of daily living (ADL) and instrumental ADL (IADL). Falls were measured prospectively for 1 year using monthly falls diaries. RESULTS: Declining cognition was associated with increased number of mobility activities designated as risky (1.5% of mobility activities performed in a risky manner per SPMSQ point) and with increased rate of falls (rate ratio=1.16 for each unit change in SPMSQ score). Risky performance of mobility activities mediated the relationship between cognition and rate of falls. LIMITATIONS: Risk assessment was based on the clinical judgment of experienced physical therapists. Cognition was measured with a relatively insensitive instrument, and only selected mobility activities were evaluated. CONCLUSIONS: Engagement in mobility ADL and IADL tasks in a risky manner emerged as a link between declining cognition and increased number of falls, suggesting a mechanism through which the rate of falls may increase. Specifically, declining cognition is associated with performance of mobility activities in an unsafe manner, thereby increasing the risk for falls. PMID- 24231228 TI - Conservative treatment of a proximal full-thickness biceps brachii muscle tear in a special operations soldier. AB - BACKGROUND: A transection of the short head of the biceps brachii muscle is an uncommon injury seen among outpatient sports physical therapy clinics. The highest rate of occurrence and the majority of literature that discusses this specific injury are related to US military parachuting. The purpose of this case report is to outline the episode of care from 2 days after the injury through 6 months of conservative treatment, which consisted of therapeutic exercise, manual therapy, and cryotherapy, within an outpatient sports physical therapy clinic in a military setting. CASE DESCRIPTION: This case report outlines the initial evaluation, diagnostic imaging, treatment, and 6-month follow-up measures for a 23-year-old male patient who sustained a static line injury resulting in a full thickness tear of his biceps brachii muscle and a partial tear of the coracobrachialis muscle. OUTCOMES: The individual described in this case report reported having no functional limitations in regard to his job and leisure activities or any pain at his 6-month follow-up, with a score of 0% noted on his Shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH). Isokinetic testing revealed a 39.1% decrease in elbow flexion peak torque and a 60.8% decrease in elbow flexion total work output at this same follow-up interval. DISCUSSION: In determining the appropriate course of treatment for this injury type, conservative physical therapy intervention should be considered as a viable treatment option, as there have been no decisive studies to suggest superior outcomes with other methods such as surgical correction. It is further recommended that research be conducted in an effort to prevent such injuries from occurring, as this mechanism of injury has proven to be much higher among the US military population compared with other military populations. PMID- 24231229 TI - Validity of the AM-PAC "6-Clicks" inpatient daily activity and basic mobility short forms. AB - BACKGROUND: Standardized assessment of patients' activity limitations in acute care settings can provide valuable information. Existing measures have not been widely implemented. OBJECTIVES: The aim of this study was to provide evidence for validity of scores on Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" measures of basic mobility and daily activity in acute care. DESIGN: A retrospective measurement study was conducted. METHODS: The study used a database from one health system containing "6-Clicks" scores from first and last physical therapist and occupational therapist visits for 84,446 patients. Validity was analyzed by examining differences in "6-Clicks" scores across categories of patient characteristics; the ability of "6-Clicks" scores to predict patients' having more than one therapy visit; correlation of "6-Clicks" scores with Functional Independence Measure (FIM) scores; and internal responsiveness over the episode of care. Internal consistency reliability also was determined. RESULTS: The "6-Clicks" scores differed across patients' age, preadmission living situation, and number of therapy visits. The areas under receiver operating characteristic curves derived using "6-Clicks" scores at the first visit to predict patients receiving more than one visit were 0.703 and 0.652 using basic mobility and daily activity scores, respectively. The "6-Clicks" scores at the final visit were correlated with scores on subscales of the FIM completed on admission to inpatient rehabilitation facilities (r=.65 and .69). Standardized response means were 1.06 and 0.95 and minimal detectable changes with 90% confidence level (MDC90) were 4.72 and 5.49 for basic mobility and daily activity scores, respectively. Internal consistency reliability of basic mobility and daily activity scores was .96 and .91, respectively. LIMITATIONS: Using clinical databases for research purposes has limitations, including missing data, misclassifications, and selection bias. Rater reliability is not known. CONCLUSIONS: This study provides evidence for the validity of "6-Clicks" scores for assessing patients' activity limitations in acute care settings. PMID- 24231230 TI - Knee pain during daily tasks, knee osteoarthritis severity, and widespread pain. AB - BACKGROUND: The presence of widespread pain is easily determined and is known to increase the risk for persistent symptoms. OBJECTIVE: The study hypothesis was that people with no or minimal knee osteoarthritis (OA) and high Western Ontario and McMaster Universities (WOMAC) Pain Scale scores would be more likely than other subgroups to report widespread pain. DESIGN: A cross-sectional design was used. METHODS: Data were obtained from the Multicenter Osteoarthritis Study, which includes people with or at high risk for knee OA. The inclusion criteria were met by 755 people with unilateral knee pain and 851 people with bilateral knee pain. Widespread pain was assessed with body diagrams, and radiographic Kellgren-Lawrence grades were recorded for each knee. Knee pain during daily tasks was quantified with WOMAC Pain Scale scores. RESULTS: Compared with people who had high levels of pain and knee OA, people with a low level of pain and a high level of knee OA, and people with low levels of pain and knee OA, a higher proportion of people with a high level of knee pain and a low level of knee OA had widespread pain. This result was particularly true for people with bilateral knee pain, for whom relative risk estimates ranged from 1.7 (95% confidence interval=1.2-2.4) to 2.3 (95% confidence interval=1.6-3.3). LIMITATIONS: The cross-sectional design was a limitation. CONCLUSIONS: People with either no or minimal knee OA and a high level of knee pain during daily tasks are particularly likely to report widespread pain. This subgroup is likely to be at risk for not responding to knee OA treatment that focuses only on physical impairments. Assessment of widespread pain along with knee pain intensity and OA status may assist physical therapists in identifying people who may require additional treatment. PMID- 24231232 TI - Innate lymphoid cells: new paradigm in immunology of inflammation. AB - Immune system is well characterized by immunologists into two major arms called innate immunity and adaptive immunity. However, recent advances in the field of immunology has led to the identification of specific immune cells, which lack signature signs of mature lymphocytes (i.e. antigen receptors), yet produce major cytokines (i.e. IFN-gamma, IL-4, IL-5, IL-13, IL-9, etc.) of helper T (Th) cell mediated immune response. Therefore, these cells can be represented as the innate counterpart of helper T cells of adaptive immunity and are known as innate lymphoid cells (ILCs). These ILCs comprise of three different groups having different kinds of cells, i.e. group 1 (NK cells and ILC1 cells), group 2 and group 3 ILCs. However, they are also emerging as novel regulators of both chronic as well as acute inflammation induced by infection or caused by sterile inflammation. Therefore, an attempt has been made to highlight the regulatory role of ILCs during inflammation and modulation of these cells as novel tissue protective mechanism. PMID- 24231231 TI - A path model for evaluating dosing parameters for children with cerebral palsy. AB - Dosing of pediatric rehabilitation services for children with cerebral palsy (CP) has been identified as a national priority. Establishing dosing parameters for pediatric physical therapy interventions is critical for informing clinical decision making, health policy, and guidelines for reimbursement. The purpose of this perspective article is to describe a path model for evaluating dosing parameters of interventions for children with CP. The model is intended for dose related and effectiveness studies of pediatric physical therapy interventions. The premise of the model is: Intervention type (focus on body structures, activity, or the environment) acts on a child first through the family, then through the dose (frequency, intensity, time), to yield structural and behavioral changes. As a result, these changes are linked to improvements in functional independence. Community factors affect dose as well as functional independence (performance and capacity), influencing the relationships between type of intervention and intervention responses. The constructs of family characteristics; child characteristics (eg, age, level of severity, comorbidities, readiness to change, preferences); plastic changes in bone, muscle, and brain; motor skill acquisition; and community access warrant consideration from researchers who are designing intervention studies. Multiple knowledge gaps are identified, and a framework is provided for conceptualizing dosing parameters for children with CP. PMID- 24231233 TI - Tuberculosis vaccine: time to look into future. AB - Global burden of tuberculosis is nearly 12 million. As per the WHO Global TB Report 2013, there were an estimated 8.6 million incident cases of TB globally in 2012. Tuberculosis is an issue that affects development through its effect on the health of individuals and families. In humans, neither prior latent infection nor recovery from active TB confers reliable protection against reinfection or reactivation disease. The power of vaccines as a public health intervention lies in their ability to reduce onward transmission of disease as much as in their ability to protect vaccinated individuals; a feature generally referred to as "herd immunity." MVA85A is a booster vaccine, used in con-junction with BCG as part of a prime-boost strategy. BCG serves as the prime vaccination and MVA85A as the boost, operating under the theory that the addition of MVA85A will produce a better immune response and more protection against TB than BCG vaccination alone. There is a critical need to raise the profile of TB vaccine research at the community, national, regional, and global levels in order to generate support and political will, increase investment, create an enabling and supportive environment for clinical trials, and lay the groundwork for acceptance and adoption of new TB vaccines once licensed. PMID- 24231234 TI - Redefining the target early during treatment. Can we visualize regional differences within the target volume using sequential diffusion weighted MRI? AB - PURPOSE: In head and neck cancer, diffusion weighted MRI (DWI) can predict response early during treatment. Treatment-induced changes and DWI-specific artifacts hinder an accurate registration between apparent diffusion coefficient (ADC) maps. The aim of the study was to develop a registration tool which calculates and visualizes regional changes in ADC. METHODS: Twenty patients with stage IV HNC treated with primary radiotherapy received an MRI including DWI before and early during treatment. Markers were manually placed at anatomical landmarks on the different modalities at both time points. A registration method, consisting of a fully automatic rigid and nonrigid registration and two semi automatic thin-plate spline (TPS) warps was developed and applied to the image sets. After each registration step the mean registration errors were calculated and DeltaADC was compared between good and poor responders. RESULTS: Adding the TPS warps significantly reduced the registration error (in mm, 6.3 +/- 6.2 vs 3.2 +/- 3.3 mm, p<0.001). After the marker based registration the median DeltaADC in poor responders was significantly lower than in good responders (7% vs. 21%; p<0.001). CONCLUSIONS: This registration method allowed for a significant reduction of the mean registration error. Furthermore the voxel-wise calculation of the DeltaADC early during radiotherapy allowed for a visualization of the regional differences of DeltaADC within the tumor. PMID- 24231235 TI - Atherosclerotic lesions in lymphoma survivors treated with radiotherapy. AB - BACKGROUND AND PURPOSE: Radiotherapy causes premature atherosclerosis in Hodgkin's lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients. MATERIAL AND METHODS: Forty three HLSs (median age 50 years, range 38-63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5-13 years after treatment. A second follow-up (FU-2) occurred 18-27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients. RESULTS: Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (beta 308 (95% CI 213-403), p < 0.001), PAS (beta 3.67 (95% CI 2.29-5.04), p < 0.001) and peripheral endothelial dysfunction (beta 2.74 (95% CI 0.47-5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001). CONCLUSION: Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol. PMID- 24231236 TI - Dose/volume-response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions. AB - BACKGROUND AND PURPOSE: Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. MATERIALS AND METHODS: The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. RESULTS: The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55-70 Gy), using both the planned and the motion inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs=0.12 0.21; Rs=0.11-0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs=0.13, p=0.02). CONCLUSION: Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power. PMID- 24231237 TI - Correlation of dose computed using different algorithms with local control following stereotactic ablative radiotherapy (SABR)-based treatment of non-small cell lung cancer. AB - PURPOSE: To retrospectively compute dose distributions for lung cancer patients treated with SABR, and to correlate dose distributions with outcome using a tumor control probability (TCP) model. METHODS: Treatment plans for 133 NSCLC patients treated using 12 Gy/fxn * 4 (BED=106 Gy), and planned using a pencil-beam (1D equivalent-path-length, EPL-1D) algorithm were retrospectively re-calculated using model-based algorithms (including convolution/superposition, Monte Carlo). 4D imaging was performed to manage motion. TCP was computed using the Marsden model and associations between dose and outcome were inferred. RESULTS: Mean D95 reductions of 20% (max.=33%) were noted with model-based algorithms (relative to EPL-1D) for the smallest tumors (PTV<20 cm(3)), corresponding to actual delivered D95 BEDs of ~ 60-85 Gy. For larger tumors (PTV>100 cm(3)), D95 reductions were ~ 10% (BED>100 Gy). Mean lung doses (MLDs) were 15% lower for model-based algorithms for PTVs<20 cm(3). No correlation between tumor size and 2-year local control rate was observed clinically, consistent with TCP calculations, both of which were ~ 90% across all PTV bins. CONCLUSION: Results suggest that similar control rates might be achieved for smaller tumors using lower BEDs relative to larger tumors. However, more studies with larger patient cohorts are necessary to confirm this possible finding. PMID- 24231238 TI - Cold spot mapping inferred from MRI at time of failure predicts biopsy-proven local failure after permanent seed brachytherapy in prostate cancer patients: implications for focal salvage brachytherapy. AB - BACKGROUND AND PURPOSE: (1) To establish a method to evaluate dosimetry at the time of primary prostate permanent implant (pPPI) using MRI of the shrunken prostate at the time of failure (tf). (2) To compare cold spot mapping with sextant-biopsy mapping at tf. MATERIAL AND METHODS: Twenty-four patients were referred for biopsy-proven local failure (LF) after pPPI. Multiparametric MRI and combined-sextant biopsy with a central review of the pathology at tf were systematically performed. A model of the shrinking pattern was defined as a Volumetric Change Factor (VCF) as a function of time from time of pPPI (t0). An isotropic expansion to both prostate volume (PV) and seed position (SP) coordinates determined at tf was performed using a validated algorithm using the VCF. RESULTS: pPPI CT-based evaluation (at 4weeks) vs. MR-based evaluation: Mean D90% was 145.23+/-19.16Gy [100.0-167.5] vs. 85.28+/-27.36Gy [39-139] (p=0.001), respectively. Mean V100% was 91.6+/-7.9% [70-100%] vs. 73.1+/-13.8% [55-98%] (p=0.0006), respectively. Seventy-seven per cent of the pathologically positive sextants were classified as cold. CONCLUSIONS: Patients with biopsy-proven LF had poorer implantation quality when evaluated by MRI several years after implantation. There is a strong relationship between microscopic involvement at tf and cold spots. PMID- 24231240 TI - Trajectory modulated prone breast irradiation: a LINAC-based technique combining intensity modulated delivery and motion of the couch. AB - PURPOSE: External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast. METHODS AND MATERIALS: A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeamTM STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom. RESULTS: The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V50% and V100% parameters that have been correlated with EBRT toxicity. CONCLUSIONS: The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose-volume parameters correlated with toxicity. PMID- 24231239 TI - The prostate cancer risk stratification (ProCaRS) project: recursive partitioning risk stratification analysis. AB - BACKGROUND: The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. METHODS: The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. RESULTS: The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ?6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ?87.5% OR PSA >30). CONCLUSIONS: Proposed RS subcategories have been identified by a RPA of the ProCaRS database. PMID- 24231241 TI - Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. AB - PURPOSE: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy * 10. In dose level 2, patients received 5 Gy * 5 (every other day). In dose level 3, patients received 5 Gy * 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. RESULTS: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. CONCLUSIONS: This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications. PMID- 24231242 TI - High-dose-rate brachytherapy alone given as two or one fraction to patients for locally advanced prostate cancer: acute toxicity. AB - BACKGROUND: To evaluate early urinary (GU) and gastrointestinal (GI) adverse events (AEs) after two or one fraction of high-dose rate brachytherapy (HDR-BT) in advanced prostate cancer. PATIENTS AND METHODS: 165 patients were treated with 2 * 13 Gy (n=115), or a single dose of 19 Gy (n=24) or 20 Gy (n=26) HDR-BT. Early AEs were assessed using the RTOG scoring system and the International Prostate Symptom Score (IPSS). RESULTS: Week-2 prevalence of severe IPSS symptoms was higher after 20 Gy than after 26 or 19 Gy but by 12 weeks all groups were at pre treatment levels or less. Grade-3 GU toxicity was observed <=9% of patients. No Grade 4 GU and no Grade 3 or 4 GI complications were observed. However, there was a significant increase in catheter use in the first 12 weeks after implant after 19 and 20 Gy compared with 2 * 13 Gy. CONCLUSION: Single dose HDR-BT is feasible with acceptable levels of acute complications; tolerance may have been reached with the single 19 Gy schedule. PMID- 24231243 TI - Intensity modulated radiosurgery of brain metastases with flattening filter-free beams. AB - PURPOSE: Flattening filter free (FFF) irradiation potentially reduces treatment delivery time in radiosurgery thus eliminating intrafraction motion and increasing patient comfort. We compared plan quality and efficiency of VMAT and IMRT plans for FFF- and standard delivery for brain metastases with single fraction doses of 20 Gy and validated the dosimetric accuracy of the FFF delivery. MATERIAL AND METHODS: CT data of 15 patients with brain metastases were included in this study. For every patient, 2 IMRT- and 2 VMAT-plans were created using a high-resolution MLC with two different delivery modes (6MV standard vs. 6MV FFF). Plan quality and efficiency was assessed by analysis of conformity, homogeneity, dose gradients, treatment delivery time and number of monitor units (MU). Dosimetric evaluation was performed for 10 FFF plans with radiochromic film and ion chamber. RESULTS: Plan quality was similar for both approaches. FFF provided a mean treatment time reduction of 51.5% with similar MU for VMAT and IMRT for this low-modulation paradigm. The dosimetric validations showed an absolute dose deviation of +0.93 +/- 0.99% and gamma-index analysis (3%/3mm and 3%/1mm) resulted in agreement of 99.08 +/- 1.58% respectively 93.46 +/- 2.41%. CONCLUSION: FFF radiosurgery is an efficient technique for intensity modulated hypofractionated or single fraction treatments with similar plan quality when compared to flattened beams at reduced treatment time. PMID- 24231244 TI - DCE-MRI of the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinoma xenografts. AB - BACKGROUND AND PURPOSE: Locoregional treatment failure and poor survival rates are associated with extensive hypoxia in the primary tumor in advanced cervical carcinoma. The potential of gadolinium diethylene-triamine penta-acetic acid (Gd DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinomas was investigated in this preclinical study. MATERIALS AND METHODS: CK-160 and TS-415 cervical carcinoma xenografts were used as tumor models. DCE-MRI was carried out at 1.5 T, and parametric images of K(trans) and v(e) were produced by pharmacokinetic analysis of the DCE-MRI series. Pimonidazole was used as a hypoxia marker. Tumor radioresponsiveness was determined by irradiating tumors with five fractions of 4 Gy in 48 h and measuring cell survival in vitro. Metastatic propensity was determined by examining host mice for tumor growth in lymph nodes. RESULTS: Low values of K(trans) were associated with extensive hypoxia and radiation resistance in tumors of both lines and with high incidence of metastases in CK-160 tumors. Associations between ve and hypoxia, radioresponsiveness, or metastatic propensity were not found in any of the tumor lines. CONCLUSION: K(trans) is a potentially useful biomarker of tumor hypoxia, radiation resistance, and metastatic growth in advanced cervical carcinoma. PMID- 24231245 TI - Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. AB - BACKGROUND AND PURPOSE: To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity. RESULTS: With a median follow up of 50 months (range, 5-115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa-b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (chi(2) = 26.32, P<0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (chi(2) = 65.54, P<0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1-2. CONCLUSION: IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage. PMID- 24231246 TI - The characteristics of physical activity and gait in patients receiving radiotherapy in cancer induced bone pain. AB - BACKGROUND AND PURPOSE: An objective measure of pain relief may add important information to patients' self assessment, particularly after a treatment. The study aims were to determine whether measures of physical activity and/or gait can be used in characterizing cancer-induced bone pain (CIBP) and whether these biomarkers are sensitive to treatment response, in patients receiving radiotherapy (XRT) for CIBP. MATERIALS AND METHODS: Patients were assessed before (baseline) and 6-8weeks after XRT (follow up). The following assessments were done: Brief Pain Inventory (BPI), activPALTM activity meter, and GAITRite(r) electronic walkway (measure of gait). Wilcoxon, Mann-Whitney and Pearson statistical analyses were done. RESULTS: Sixty patients were assessed at baseline; median worst pain was 7 and walking interference was 5. At follow up 42 patients were assessed. BPI worst pain, average pain, walking interference and total functional interference all improved (p<0.001). An improvement in functional interference correlated with aspects of physical activity (daily hours standing r=0.469, p=0.002) and gait (cadence r=0.341, p=0.03). The activPAL and GAITRite parameters did not change following XRT (p>0.05). In responder analyses there were no differences in activPAL and GAITRite parameters (p>0.05). CONCLUSION: Assessment of physical activity and gait allow a characterization of the functional aspects of CIBP, but not in the evaluation of XRT. PMID- 24231247 TI - Damage accumulation location under cyclic loading in the lumbar disc shifts from inner annulus lamellae to peripheral annulus with increasing disc degeneration. AB - It is difficult to study the breakdown of lumbar disc tissue over several years of exposure to bending and lifting by experimental methods. In our earlier published study we have shown how a finite element model of a healthy lumbar motion segment was used to predict the damage accumulation location and number of cyclic to failure under different loading conditions. The aim of the current study was to extend the continuum damage mechanics formulation to the degenerated discs and investigate the initiation and progression of mechanical damage. Healthy disc model was modified to represent degenerative discs (Thompson grade III and IV) by incorporating both geometrical and biochemical changes due to degeneration. Analyses predicted decrease in the number of cycles to failure with increasing severity of disc degeneration. The study showed that the damage initiated at the posterior inner annulus adjacent to the endplates and propagated outwards towards its periphery in healthy and grade III degenerated discs. The damage accumulated preferentially in the posterior region of the annulus. However in grade IV degenerated disc damage initiated at the posterior outer periphery of the annulus and propagated circumferentially. The finite element model predictions were consistent with the infrequent occurrence of rim lesions at early age but a much higher incidence in severely degenerated discs. PMID- 24231248 TI - Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin. AB - Stem cell-based engineering strategies for tendons have yet to yield a normal functional tissue, due in part to a need for tenogenic factors. Additionally, the ability to evaluate differentiation has been challenged by a lack of markers for differentiation. We propose to inform tendon regeneration with developmental cues involved in normal tissue formation and with phenotypic markers that are characteristic of differentiating tendon progenitor cells (TPCs). Mechanical forces, fibroblast growth factor (FGF)-4 and transforming growth factor (TGF) beta2 are implicated in embryonic tendon development, yet the isolated effects of these factors on differentiating TPCs are unknown. Additionally, developmental mechanisms vary between limb and axial tendons, suggesting the respective cell types are programmed to respond uniquely to exogenous factors. To characterize developmental cues and benchmarks for differentiation toward limb vs. axial phenotypes, we dynamically loaded and treated TPCs with growth factors and assessed gene expression profiles as a function of developmental stage and anatomical origin. Based on scleraxis expression, TGFbeta2 was tenogenic for TPCs at all stages, while loading was for late-stage cells only, and FGF4 had no effect despite regulation of other genes. When factors were combined, TGFbeta2 continued to be tenogenic, while FGF4 appeared anti-tenogenic. Various treatments elicited distinct responses by axial vs. limb TPCs of specific stages. These results identified tenogenic factors, suggest tendon engineering strategies should be customized for tissues by anatomical origin, and provide stage-specific gene expression profiles of limb and axial TPCs as benchmarks with which to monitor tenogenic differentiation of stem cells. PMID- 24231249 TI - Cooperative effects in FH/Li?HCCX?OH2 complexes (X=F, Cl, Br, H). AB - The dimers with general formula FH/FLi?HCCX and HCCX?OH2, and the trimers FH?HCCX?OH2 (X=F, Cl, Br, H), were optimized computationally to stable structures. These model systems derive their strength from a combination of H?pi (or Li?pi) electrostatic interactions in the T-shaped FH/FLi?HCCX dimers and halogen bonding between the X and the O atom of H2O (or CH?O hydrogen-bonding in HCCH complexes). These cooperative interactions in the trimer clusters yield a non-additive energy which enhances the stability by between 7% and 10%. The variation in the interaction energies, as well as other selected properties, for different X is rationalized and discussed. PMID- 24231250 TI - False-positive pneumococcal antigen test in a case of Enterococcus faecalis meningitis. PMID- 24231251 TI - Telomere length and risk of glioma. AB - BACKGROUND: Telomere length in blood or buccal cell DNA has been associated with risk of various cancers. Glioma can be a highly malignant brain tumor and has few known risk factors. Genetic variants in or near RTEL1 and TERT, key components of telomere biology, are associated with glioma risk. Therefore, we evaluated the association between relative telomere length (RTL) and glioma in a prospective study. MATERIALS AND METHODS: We performed a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. RTL was determined by quantitative PCR on blood or buccal cell DNA obtained at least 2 years prior to diagnosis from 101 individuals with glioma cases. Healthy controls (n=198) were matched to cases (2:1) on age, gender, smoking status, calendar year, and DNA source. Conditional logistic regression was used to investigate the association between RTL and glioma. RESULTS: As expected, RTL declined with increasing age in both cases and controls. There was no statistically significant association between RTL and glioma overall. An analysis stratified by gender suggested that short RTL (1st tertile) in males was associated with glioma (odds ratio, [OR]=2.29, 95% confidence interval [CI] 1.02-5.11); this association was not observed for females (OR=0.41, 95% CI 0.14-1.17). CONCLUSIONS: This prospective study did not identify significant associations between RTL and glioma risk, but there may be gender-specific differences. Larger, prospective studies are needed to evaluate these findings. PMID- 24231253 TI - 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer. AB - Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type. PMID- 24231252 TI - DNA sequence-dependent mechanics and protein-assisted bending in repressor mediated loop formation. AB - As the chief informational molecule of life, DNA is subject to extensive physical manipulations. The energy required to deform double-helical DNA depends on sequence, and this mechanical code of DNA influences gene regulation, such as through nucleosome positioning. Here we examine the sequence-dependent flexibility of DNA in bacterial transcription factor-mediated looping, a context for which the role of sequence remains poorly understood. Using a suite of synthetic constructs repressed by the Lac repressor and two well-known sequences that show large flexibility differences in vitro, we make precise statistical mechanical predictions as to how DNA sequence influences loop formation and test these predictions using in vivo transcription and in vitro single-molecule assays. Surprisingly, sequence-dependent flexibility does not affect in vivo gene regulation. By theoretically and experimentally quantifying the relative contributions of sequence and the DNA-bending protein HU to DNA mechanical properties, we reveal that bending by HU dominates DNA mechanics and masks intrinsic sequence-dependent flexibility. Such a quantitative understanding of how mechanical regulatory information is encoded in the genome will be a key step towards a predictive understanding of gene regulation at single-base pair resolution. PMID- 24231254 TI - The influence of upper-body strength on flat-water sprint kayak performance in elite athletes. AB - Dry-land strength training is a fundamental component for elite kayak performance. The aims of this research were 3-fold: 1st, to determine the relationship between performance time and strength scores for elite kayakers; 2nd, to identify how strength changes (gains or losses) over 3 training y relate with changes in performance time for elite kayakers; and 3rd, to compare the progression in performance times for elite athletes with the top 3 performers from the national championships. The performance data for 15 elite male and 10 elite female kayakers were collected over 2 y. This group was reduced to 9 men and 8 women in the 3rd and final year. There were direct and significant correlations between strength scores and performance times across the 3 y. Bench press 1RM increased by 34.8% for men and 42.3% for women. Over the 3 seasons, mean 1000-m time decreased by approximately 4.8%, 500-m times decreased by 7.3% (women), and 200-m times decreased by 9.1%. The women's 500-m changed from 11.9% difference from medalists to within 1.1% during the 3 y. During the 3 y of this study a change in 1-repetitionmaximum (1RM) bench press of 13% for men and 6.5% in women coincided with a change in performance times of 1%. For 1RM pull-up a change of 10% in men and 2.3% in women coincided with a change in performance times of 1%. PMID- 24231255 TI - Response to the letter by Dubey et al. (2013). PMID- 24231256 TI - Results of the European Basic Laparoscopic Urological Skills examination. AB - BACKGROUND: In 2011, the European Basic Laparoscopic Urological Skills (E-BLUS) examination was introduced as a pilot for the examination of final-year urologic residents. OBJECTIVE: In this study, we aimed to answer the following research questions: What level of laparoscopic skills do final-year residents in urology have in Europe, and do the participants of the E-BLUS pass the examination according to the validated criteria? DESIGN, SETTING, AND PARTICIPANTS: Participants of the examination were final-year urology residents from different European countries taking part in the European Urology Residents Education Program in 2011 and 2012. SURGICAL PROCEDURE: The E-BLUS exam consists of five tasks validated for the training of basic urologic laparoscopic skills. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performances of the tasks were recorded on DVD and analysed by an objective rater. Time and number of errors made in tasks 1 4 were noted. Furthermore, all expert laparoscopic urologists were asked to score participants on a global rating scale (1-5) based on three items: depth perception, bimanual dexterity, and efficiency. Participants were asked to complete a questionnaire on prior training and laparoscopic experience. RESULTS AND LIMITATIONS: Seventy DVD recordings were analysed. Most participants did not pass the time criteria on task 4 (90%), task 2 (85.7%), task 1 (74.3%), and task 5 (71.4%). Task 3 was passed by 84.3%. The overall quality score was passed by 64%. When combining time and quality, only three participants (4.2%) passed the examination according to the validated criteria. According to the questionnaire, 61% did not have the opportunity to train in laparoscopic skills. CONCLUSIONS: The results of the E-BLUS examination show that the level of basic laparoscopic skills among European residents is low. Although quality of performance is good, most residents do not pass the validated time criteria. Regular laparoscopic training or a dedicated fellowship should improve the laparoscopic level of residents in urology. PMID- 24231257 TI - Understanding community pharmacy intervention practice: lessons from intervention researchers. AB - BACKGROUND: Community pharmacy (CP) is a setting with health promotion and public health potential which could include strategies with a nutrition promotion focus. Research embedded in this setting has explored and produced evidence to inform practice change to develop this potential. The experience of undertaking research in this setting may provide insight into the challenges and key features of intervention research practice. Exploring experienced-based knowledge presents as a productive area of research, extending what can be known beyond the bounds of what is measurable. OBJECTIVES: This study aimed to understand the experience of intervention research in CP with a focus on nutrition and to develop guidance for future research practice (intervention design and implementation) in CP based on interventionists' reflections and practice wisdom. METHODS: Semi-structured interviews were conducted with 9 researchers with experience in undertaking intervention research in CP with a nutrition component. Content analysis, constant comparison and interpretive description were used in the analysis and interpretation of interview data. RESULTS: Five key lessons were identified - 1) utilize existing capacity; 2) navigate and utilize social power and interests; 3) personalize engagement and recruitment; 4) consider the logistics and 5) intervention type considerations. Key challenges for translating research into practice and sustaining change included financial sustainability, physical constraints, logistics, collaboration, and practice change enablers. Personal reflections on research practice identified qualities, such as determination and skills in networking, as key for researching in CP. CONCLUSIONS: CP-embedded research is challenging given the complexity of the practice environment. The social context of CP appears central to intervention research and a nuanced understanding of the social context needs to be the basis for intervention design to inform successful implementation. Experience-based and insider knowledge is useful and needed for nuanced design and development of intervention research in CP. PMID- 24231258 TI - IgA+ plasma cells in murine intestinal lamina propria as a positive regulator of Treg differentiation. AB - Continuous exposure to commensal bacteria gives rise to a complex intestinal immune system that maintains local tolerance, which requires Foxp3-expressing Treg. Recently, the regulation of TFH function by plasma cells has been reported, but effects of intestinal LP-PCs, one of the richest plasma cells in the body, on T cell differentiation have not been studied. Here, we investigated whether IgA(+) LP-PCs from murine small intestines had effects on T cell differentiation. Surprisingly, when IgA(+) LP-PCs were cocultured with CD4(+) T cells, Foxp3 expression was increased significantly in CD4(+)CD25(-) T cells. Results using the Transwell coculture system revealed that soluble factors from LP-PCs, TGF beta, and RA were involved in the induction of Foxp3 expression. Furthermore, Foxp3(+)CD25(-) T cells were decreased in PP after intestinal depletion of plasma cells. In addition, intestinal colony transfer from SPF to germ-free mice was demonstrated to generate IgA(+) LP-PCs and Foxp3(+) T cells with meaningful correlation in LP. We report for the first time that IgA(+) LP-PCs induce Foxp3 expression in T cells through TGF-beta and RA. LP-PCs generated by commensal bacteria may play a crucial role in intestinal immunity through the induction of Treg, as well as IgA production. PMID- 24231259 TI - Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors. AB - Effector and memory CD4 and CD8 T cell responses are critical for the control of many intracellular pathogens. The development of these populations is governed by transcription factors that molecularly control their differentiation, function, and maintenance. Two transcription factors known to be involved in these processes are Tbet and STAT4. Although Tbet has been shown to regulate CD8 T cell fate decisions and effector CD4 T cell choices, the contribution of STAT4 is less well understood. To address this, we examined the impact of STAT4 on T cell responses in the presence or absence of Tbet, following LCMV infection by using mice lacking Tbet, STAT4, or both transcription factors. STAT4 was not required for Tbet or Eomes expression; however, virus-specific effector CD8 T cells are skewed toward a memory-precursor phenotype in the absence of STAT4. This altered proportion of memory precursors did not result in an increase in memory CD8 T cells after the resolution of the infection. We also demonstrate that virus specific effector and memory CD4 T cells formed independently of Tbet and STAT4, although a slight reduction in the number of antigen-specific CD4 T cells was apparent in mice lacking both transcription factors. Collectively, we have discovered distinct roles for Tbet and STAT4 in shaping the phenotype and function of virus-specific T cell responses. PMID- 24231260 TI - Population heterogeneity in the salience of multiple risk factors for adolescent delinquency. AB - PURPOSE: To present mixture regression analysis as an alternative to more standard regression analysis for predicting adolescent delinquency. We demonstrate how mixture regression analysis allows for the identification of population subgroups defined by the salience of multiple risk factors. METHODS: We identified population subgroups (i.e., latent classes) of individuals based on their coefficients in a regression model predicting adolescent delinquency from eight previously established risk indices drawn from the community, school, family, peer, and individual levels. The study included N = 37,763 10th-grade adolescents who participated in the Communities That Care Youth Survey. Standard, zero-inflated, and mixture Poisson and negative binomial regression models were considered. RESULTS: Standard and mixture negative binomial regression models were selected as optimal. The five-class regression model was interpreted based on the class-specific regression coefficients, indicating that risk factors had varying salience across classes of adolescents. CONCLUSIONS: Standard regression showed that all risk factors were significantly associated with delinquency. Mixture regression provided more nuanced information, suggesting a unique set of risk factors that were salient for different subgroups of adolescents. Implications for the design of subgroup-specific interventions are discussed. PMID- 24231261 TI - Mean girls: sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour. AB - Clinical studies indicate that children who experience a traumatic brain injury (TBI) are often the victim of peer rejection, have very few mutual friends, and are at risk for long-term behavioural and social impairments. Owing to the fact that peer play is critical for healthy development, it is possible that the long term impairments are associated not only with the TBI, but also altered play during this critical period of brain development. This study was designed to determine if social dynamics and juvenile play are altered in rats that experience a mild TBI (mTBI) early in life. Play-fighting behaviours were recorded and analyzed for young male and female Sprague Dawley rats that were given either an mTBI or a sham injury. The study found that the presence of an mTBI altered the play fighting relationship, and the nature of the alterations were dependent upon the sex of the pairing and the injury status of their peers. Sham rats were significantly less likely to initiate play with an mTBI rat, and were more likely to respond to a play initiation from an mTBI rat with an avoidant strategy. This effect was significantly more pronounced in female rats, whereby it appeared that female rats with an mTBI were particularly rejected and most often excluded from play experiences. Male rats with an mTBI learned normal play strategies from their sham peers (when housed in mixed cages), whereas female rats with an mTBI show heightened impairment in these conditions. Play therapy may need to be incorporated into treatment strategies for children with TBI. PMID- 24231262 TI - Synthesis and characterization of cellulose 3,5-dimethylphenylcarbamate silica hybrid spheres for enantioseparation of chiral beta-blockers. AB - A cellulose derivative-based chiral stationary phase (CSP) is considered one of the most widely applied CSPs due to its powerful enantioseparation ability. The high loading capacity and mechanical strength of CSPs are crucial for their application in preparative chromatography, such as a simulated moving bed. Compared to traditional cellulose-based CSPs that have been adsorbed onto chromatographic supports, organic-inorganic hybrid CSPs exhibit a potentially higher loading capacity and mechanical strength by increasing the density of chiral recognition groups. A hybrid cellulose 3,5-dimethylphenylcarbamate chiral stationary phase (organic/inorganic: 70/30, w/w) was prepared via a sol-gel method and characterized with several analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and (29)Si cross polarization/magic angle spinning nuclear magnetic resonance ((29)Si CP/MAS NMR). In addition, the as synthesized hybrid chiral silica spheres were treated with an end-capping process to mask the residual silica hydroxyl groups. Compared to a commercial Chiralpak IB column, better separation of beta-blocker drugs, including pindolol (selectivity of 5.55), metoprolol (2.30), propranolol (1.96), bisoprolol (1.74) and atenolol (1.46), on the end-capped CSP was achieved using liquid chromatography, which suggests that the packing material synthesized in this work has sufficient chiral discriminating ability for the effective separation of beta blocker drugs. PMID- 24231263 TI - Separation of iron-free and iron-saturated forms of transferrin and lactoferrin via capillary electrophoresis performed in fused-silica and neutral capillaries. AB - A capillary electrophoresis-based method for the cost-effective and high efficient separation of iron-free and iron-saturated forms of two members of transferrin family: transferrin and lactoferrin has been developed. The proposed qualitative method relying on the SDS application allowed us to separate iron free and iron-saturated forms of these proteins, as well as human serum albumin, used as an internal standard. Owing to the distinct migration times under established conditions, the combination of transferrin and lactoferrin assays within a single analytical procedure was feasible. The performance of the method using a fused-silica capillary has been compared with the results obtained using the same method but performed with the use of a neutral capillary of the same dimensions. Neutral capillary has been used as an alternative, since the comparable resolution has been achieved with a concomitant reduction of the electroosmotic flow. Despite of this fact, the migration of analytes occurred with similar velocity but in opposite order, due to the reverse polarity application. A quantitative method employing fused-silica capillary for iron saturation study has been also developed, to evaluate the iron saturation in commercial preparations of lactoferrin. PMID- 24231264 TI - Chemical profiling and quantification of Chinese medicinal formula Huang-Lian-Jie Du decoction, a systematic quality control strategy using ultra high performance liquid chromatography combined with hybrid quadrupole-orbitrap and triple quadrupole mass spectrometers. AB - To clarify and quantify the chemical profiling of Huang-Lian-Jie-Du decoction (HLJDD) rapidly, a feasible and accurate strategy was developed by applying high speed LC combined with hybrid quadrupole-orbitrap mass spectrometer (Q-Exactive) and UHPLC-triple quadruple mass spectrometer (UHPLC-QqQ MS). 69 compounds, including iridoids, alkaloids, flavonoids, triterpenoid, monoterpene and phenolic acids, were identified by their characteristic high resolution mass data. Among them, 18 major compounds were unambiguously detected by comparing with reference standards. In the subsequent quantitative analysis, 17 representative compounds, selected as quality control markers, were simultaneously detected in 10 batches of HLJDD samples by UHPLC-QqQ MS. These samples were collected from four different countries (regions). Icariin, swertiamarin and corynoline were employed as internal standards for flavonoids, iridoids and alkaloids respectively. All the analytes were detected within 12min. Polarity switching mode was used in the optimization of multiple reaction monitoring (MRM) conditions. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r(2)>0.9990). The relative standard deviations (RSD) of inter- and intra-day precisions were less than 5.0%. This method was also validated by repeatability, stability (8h) and recovery, with respective RSDs less than 4.6%, 5.0% and 6.3%. This research established a high sensitive and efficient method for the integrating quality control, including identification and quantification of Chinese medicinal formulas. PMID- 24231265 TI - Fermentation pre-treatment of landfill leachate for enhanced electron recovery in a microbial electrolysis cell. AB - Pre-fermentation of poorly biodegradable landfill leachate (BOD5/COD ratio of 0.32) was evaluated for enhanced current density (j), Coulombic efficiency (CE), Coulombic recovery (CR), and removal of organics (BOD5 and COD) in a microbial electrolysis cell (MEC). During fermentation, the complex organic matter in the leachate was transformed to simple volatile fatty acids, particularly succinate and acetate in batch tests, but mostly acetate in semi-continuous fermentation. Carbohydrate had the highest degree of fermentation, followed by protein and lipids. j, CE, CR, and BOD5 removal were much greater for an MEC fed with fermented leachate (23 A/m(3) or 16 mA/m(2), 68%, 17.3%, and 83%, respectively) compared to raw leachate (2.5 A/m(3) or 1.7 mA/m(2), 56%, 2.1%, and 5.6%, respectively). All differences support the value of pre-fermentation before an MEC for stabilization of BOD5 and enhanced electron recovery as current when treating a recalcitrant wastewater like landfill leachate. PMID- 24231266 TI - Study on kinetic model of microwave thermocatalytic treatment of biomass tar model compound. AB - Kinetic model parameters for toluene conversion under microwave thermocatalytic treatment were evaluated. The kinetic rate constants were determined using integral method based on experimental data and coupled with Arrhenius equation for obtaining the activation energies and pre-exponential factors. The model provides a good agreement with the experimental data. The kinetic model was also validated with standard error of 3% on average. The extrapolation of the model showed a reasonable trend to predict toluene conversion and product yield both in thermal and catalytic treatments. Under microwave irradiation, activation energy of toluene conversion was lower in the range of 3-27 kJ mol(-1) compared to those of conventional heating reported in the literatures. The overall reaction rate was six times higher compared to conventional heating. As a whole, the kinetic model works better for tar model removal in the absence of gas reforming within a level of reliability demonstrated in this study. PMID- 24231267 TI - Blood blister-like aneurysms: single center experience and systematic literature review. AB - Blood blister-like aneurysms (BBAs) are a controversial entity. They arise from non-branching sites on the supraclinoid internal carotid artery (ICA) and are suspected to originate from a dissection. Our aim is to describe the BBA cases seen in our center and to present a systematic review of the literature on BBAs. We analyzed the eleven cases of BBA admitted to our center from 2003 to 2012. We assessed the medical history, treatment modality (endovascular and/or surgery), complications and clinical outcome. The cohort included 8 women and 4 men with a mean age of 53.16 years. Treatment of the BBA consisted of stenting and coiling in 5 patients, stenting only in 4 patients, coiling and clipping in 1 patient, clipping only in 1 patient, and conservative treatment in 1 patient. A good outcome was found in 10 patients, as defined by a modified Rankin Scale (mRS) less than or equal to two at three months. A systematic review of the literature was performed, and 314 reported patients were found: 221 patients were treated with a primarily surgical approach, and 87 patients were treated with a primarily endovascular approach. A rescue or second treatment was required in 46 patients (21%). The overall estimated treatment morbidity rate was 17%, and the mortality rate was 15%. BBAs exhibit more aggressive behavior compared to saccular aneurysms, and more intra-operative complications occur with BBAs, independent of the treatment type offered. They are also significantly more likely to relapse and rebleed after treatment. Endovascular treatment offers a lower morbidity mortality compared with surgical approaches. Multilayer flow-diverting stents appear to be a promising strategy. PMID- 24231269 TI - Which functionalities are available in the electronic health record systems used by French general practitioners? An assessment study of 15 systems. AB - OBJECTIVE: Whereas an unprecedented effort is currently under way worldwide for the implementation of electronic health record (EHR) systems, their capabilities are poorly understood, especially in primary care. The objective of this study was to assess the main functionalities of the EHR systems used in French general practices. METHODS: Among the 20 EHR systems marketed in France, we assessed the 15 systems used by more than 1500 general practitioners in the Provence-Alpes Cote d'Azur region in the southeast part of France. Each EHR system was assessed in a general practice office, using two clinical vignettes describing virtual patient consultations. The evaluation criteria were derived from the EuroRec requirements for EHR system quality. The assessment scale included 37 criteria grouped into three sets: background data, consultation data, and exchange functionalities. The scoring system used, totalling 64 points, was based on the validation of the criteria and was adjusted based on the possibility of standardising the data. A high score indicated a good EHR system quality. RESULTS: The median global score was 32 points out of a possible 64 (range: 20 39). The median score was 12 points out of 22 (range: 6-15) for the background data set, 16 points out of 32 (range: 9-22) for the consultation data set, and four points out of 10 (range: 0-6) for the exchange functionalities. No association was found between the number of users and the assessment score of the EHR systems (p=0.79). One third of the EHR systems lacked a problem list and only one of them supported the episode of care. CONCLUSION: Functionalities noticeably vary among the EHR systems currently used in French primary care. Whereas these systems are globally very focused on drug prescriptions, several core functionalities are frequently lacking. They are also poorly interoperable for healthcare professionals and patients. Further research is necessary to assess their actual use. PMID- 24231268 TI - BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. AB - Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications. PMID- 24231270 TI - Rickettsial infections in ticks from wild birds in Paraguay. AB - Ticks were collected from wild birds at 3 locations in Paraguay during the South American winter in August and September 2012. In total, 480 birds belonging to 106 species were examined. Overall, 31 (6.5%) birds representing 21 species were found parasitized by ticks which were identified as Amblyomma calcaratum Neumann (2 larvae, 20 nymphs), Amblyomma longirostre (Koch) (17 larvae, 3 nymphs), Amblyomma parvum Aragao (7 nymphs), Amblyomma aureolatum (Pallas) (1 nymph), Amblyomma ovale Koch (1 nymph), Amblyomma tigrinum Koch (1 larva), and Amblyomma spp. (4 larvae). Ticks collected accidentally on humans at the study locations during field work included 1 nymph of Amblyomma coelebs Neumann and 54 nymphs of Amblyomma cajennense (Fabricius). Most ticks were individually tested for the presence of Rickettsia species by polymerase chain reaction targeting rickettsial genes gltA and ompA and by amplicon sequencing. Two (12%) out of 17 A. longirostre larvae were found infected with Candidatus 'Rickettsia amblyommii', and 2 (33%) out of 6 A. parvum nymphs were infected with Candidatus 'Rickettsia andeanae'. This study provides the first report of rickettsial infections in Paraguayan ticks. PMID- 24231271 TI - Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine. AB - The self-adjuvanting lipid core peptide (LCP) system offers a safe alternative vaccine delivery strategy, eliminating the need for additional adjuvants such as CpG Alum. In this study, we adopted the LCP as a scaffold for an epitope located on the surface of the cathepsin D hemoglobinase (Sm-CatD) of the human blood fluke Schistosoma mansoni. Sm-CatD plays a pivotal role in digestion of the fluke's bloodmeal and has been shown to be efficacious as a subunit vaccine in a murine model of human schistosomiasis. Using molecular modeling we showed that S. mansoni cathepsin D possesses a predicted surface exposed alpha-helix (A263K) that corresponds to an immunodominant helix and target of enzyme-neutralizing antibodies against Necator americanus APR-1 (Na-APR-1), the orthologous protease and vaccine antigen from blood-feeding hookworms. The A263K epitope was engineered as two peptide variants, one of which was flanked at both termini with a coil maintaining sequence, thereby promoting the helical characteristics of the native A263K epitope. Some of the peptides were fused to a self-adjuvanting lipid core scaffold to generate LCPs. Mice were vaccinated with unadjuvanted peptides, peptides formulated with Freund's adjuvants, or LCPs. Antibodies generated to LCPs recognized native Sm-CatD within a soluble adult schistosome extract, and almost completely abolished its enzymatic activity in vitro. Using immunohistochemistry we showed that anti-LCP antibodies bound to the native Sm CatD protein in the esophagus and anterior regions of the gastrodermis of adult flukes. Vaccines offer an alternative control strategy in the fight against schistosomiasis, and further development of LCPs containing multiple epitopes from this and other vaccine antigens should become a research priority. PMID- 24231272 TI - Effect of age, anthropometry, and distance in stroke parameters of young swimmers. AB - This study aimed to determine the influence of age, anthropometry, and distance on stroke parameters of 10- to 17-y-old swimmers. Forty-six male swimmers were divided into 4 chronological age groups. Anthropometry and sexual maturity were assessed, and maximal efforts of 100, 200, and 400 m using front-crawl style were performed to determine stroke rate (SR), length (SL), and index (SI). Multiple linear regression, 1-way, and mixed ANOVA for repeated measures were used for statistical analyses. There was significant effect of distance for all stroke parameters (P < .001) and an age effect only for SL and SI (P < .001). Post hoc showed that the 10- to 17-year-old group significantly reduced SR with increasing distance (effect size -0.8 to -1.5 comparing 100, 200, and 400 m) but were not effective in offsetting this adaptation with increased SL, especially from 200- to 400-m distance, at which no group made both adjustments, highlighting the decreased efficiency with significant SI reduction (effect size -0.2 to -0.4 comparing 100, 200, and 400 m). Considering all stroke parameters, the performances were almost 100% explained, but SI itself could explain around 90% of the performance; furthermore, limb length contributed to explain all stroke parameter, and SI was the variable best predicted (around 75%) by anthropometrical (upper limbs and height) and descriptive variables (age and y of systematic training).Thus, distinct effects of distance and advancing age were found during childhood and adolescence on stroke parameters, and SI was highlighted as the best predictor of 100-, 200-, and 400-m maximal performances. PMID- 24231274 TI - New US prevention guidelines focus on overall risk of cardiovascular disease. PMID- 24231275 TI - First case of human infection with new bird flu virus is confirmed. PMID- 24231273 TI - Interspinous process device versus standard conventional surgical decompression for lumbar spinal stenosis: randomized controlled trial. AB - OBJECTIVE: To assess whether interspinous process device implantation is more effective in the short term than conventional surgical decompression for patients with intermittent neurogenic claudication due to lumbar spinal stenosis. DESIGN: Randomized controlled trial. SETTING: Five neurosurgical centers (including one academic and four secondary level care centers) in the Netherlands. PARTICIPANTS: 203 participants were referred to the Leiden-The Hague Spine Prognostic Study Group between October 2008 and September 2011; 159 participants with intermittent neurogenic claudication due to lumbar spinal stenosis at one or two levels with an indication for surgery were randomized. INTERVENTIONS: 80 participants received an interspinous process device and 79 participants underwent spinal bony decompression. MAIN OUTCOME MEASURES: The primary outcome at short term (eight weeks) and long term (one year) follow-up was the Zurich Claudication Questionnaire score. Repeated measurements were made to compare outcomes over time. RESULTS: At eight weeks, the success rate according to the Zurich Claudication Questionnaire for the interspinous process device group (63%, 95% confidence interval 51% to 73%) was not superior to that for standard bony decompression (72%, 60% to 81%). No differences in disability (Zurich Claudication Questionnaire; P=0.44) or other outcomes were observed between groups during the first year. The repeat surgery rate in the interspinous implant group was substantially higher (n=21; 29%) than that in the conventional group (n=6; 8%) in the early post-surgical period (P<0.001). CONCLUSIONS: This double blinded study could not confirm the hypothesized short term advantage of interspinous process device over conventional "simple" decompression and even showed a fairly high reoperation rate after interspinous process device implantation. TRIAL REGISTRATION: Dutch Trial Register NTR1307. PMID- 24231276 TI - Essex hospital is put into special measures over breach of licence. PMID- 24231277 TI - Focus on fruits and vegetables to reduce cardiovascular disease and all-cause mortality. PMID- 24231278 TI - The control of lipid-induced inflammation by macrophages. PMID- 24231279 TI - Lipid metabolism and cancer. PMID- 24231280 TI - Choice of medical therapy to lower triglycerides in those at risk of pancreatitis. PMID- 24231282 TI - Male-specific splicing of the silkworm Imp gene is maintained by an autoregulatory mechanism. AB - Sexual differentiation in the silkworm Bombyx mori is controlled by sex-specific splicing of Bmdsx, in which exons 3 and 4 are skipped in males. B. mori insulin like growth factor II mRNA-binding protein (Imp) is a factor involved in the male specific splicing of Bmdsx. In this study, we found that the male-specific Imp mRNA is formed as a result of the inclusion of exon 8 and the promoter-distal poly(A) site choice, whereas non-sex-specific polyadenylation occurs at the promoter-proximal poly(A) site downstream of exon 7. Recent studies revealed that Drosophila Sxl, tra in several dipteran and hymenopteran insects, and fem in Apis mellifera, play a central role in sex determination and maintain their productive mode of expression via an autoregulatory function. To determine whether Imp protein is required for the maintenance of the male-specific splicing of its own pre-mRNA, we knocked down endogenous Imp in male cells and assessed the male specific splicing of an exogenous Imp minigene. Knockdown of endogenous Imp inhibited the male-specific splicing of the Imp minigene transcript. In contrast, overexpression of Imp in female cells induced the male-specific splicing of the Imp minigene transcript. Moreover, deletion of adenine-rich (A-rich) sequences located downstream of the proximal poly(A) site repressed the male-specific splicing of the Imp minigene transcript. Finally, gel shift analysis demonstrated that Imp binds to the A-rich sequences. These data suggest that Imp binds to the A-rich sequences in its own pre-mRNA to induce the male-specific splicing of its pre-mRNA. PMID- 24231283 TI - The recent multi-ethnic global lung initiative 2012 (GLI2012) reference values don't reflect contemporary adult's North African spirometry. AB - BACKGROUND: The applicability of the recent multi-ethnic reference equations derived by the ERS Global Lung Initiative (ERS/GLI) in interpreting spirometry data in North African adult subjects has not been studied. OBJECTIVE: To ascertain how well the recent ERS/GLI reference equations fit contemporary adult Tunisian spirometric data. POPULATION AND METHODS: Spirometric data were recorded from 1192 consecutive spirometry procedures in adults aged 18-60 years. Reference values and lower limits of normality (LLN) were calculated using the local and the ERS/GLI reference equations. Applied definitions: large airway obstructive ventilatory defect (LAOVD): FEV1/FVC < LLN. Tendency to a restrictive ventilatory defect (TRVD): FEV1 and FVC < LLN and FEV1/FVC >= LLN. The spirometric profile, according to the two reference equations, was determined. Z-scores for spirometry from North African healthy subjects (n = 489) were calculated. If the average Z score deviated by <+/- 0.5 from the overall mean, the ERS/GLI reference equations would be considered as reflective of contemporary Tunisian spirometry. RESULTS: Using Tunisian reference equations, 71.31%, 6.71% and 19.04% of spirometry records were interpreted as normal, and as having, LAOVD and TRVD, respectively. Using the ERS/GLI reference equations, these figures were respectively, 85.82%, 4.19% and 8.39%. The mean +/- SD Z-scores for the contemporary healthy North African subject's data were -0.55 +/- 0.87 for FEV1, -0.62 +/- 0.86 for FVC and 0.10 +/- 0.73 for FEV1/FVC. CONCLUSION: The present study don't recommend the use of the recent ERS/GLI reference equations to interpret spirometry in North African adult population. PMID- 24231284 TI - CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies. PMID- 24231285 TI - Low-affinity allergen-specific IgE in cord blood and affinity maturation after birth. PMID- 24231286 TI - Board walk - December 2013. PMID- 24231287 TI - Compressing movement information via principal components analysis (PCA): contrasting outcomes from the time and frequency domains. AB - PCA has become an increasingly used analysis technique in the movement domain to reveal patterns in data of various kinds (e.g., kinematics, kinetics, EEG, EMG) and to compress the dimension of the multivariate data set recorded. It appears that virtually all movement related PCA analyses have, however, been conducted in the time domain (PCAt). This standard approach can be biased when there are lead lag (phase-related) properties to the multivariate time series data. Here we show through theoretical derivation and analysis of simulated and experimental postural kinematics data sets that PCAt and, PCA in the frequency domain (PCAf), can lead to contrasting determinations of the dimension of a data set, with the tendency of PCAt to overestimate the number of components. PCAf also provides the possibility of obtaining amplitude and phase-difference spectra for each principal component that are uniquely suitable to reveal control mechanisms of the system. The bias in the PCAt estimate of the number of components can have significant implications for the veracity of the interpretations drawn in regard to the dynamical degrees of freedom of the perceptual-motor system. PMID- 24231288 TI - Motor palsies of cranial nerves (excluding VII) after vaccination: reports to the US Vaccine Adverse Event Reporting System. AB - We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels. PMID- 24231290 TI - Avian influenza A (H5N1) virus antibodies in pigs and residents of swine farms, southern China. AB - BACKGROUND: Since 1997, the H5 avian influenza viruses (AIVs) circulating in China have become an international concern. Clade 2.3.2 of H5N1 AIVs is genetically distinct from the viruses isolated before 2007 and antigenically different from the vaccine strains widely used in China. Swine farms in rural China are thought to play an important role in AIVs ecology. OBJECTIVES: A seroepidemiological study was undertaken among swine farm residents and pigs to understand the prevalence of antibodies against H5N1 AIVs in southern China. STUDY DESIGN: During the period March 24, 2008 to December 25, 2012,serum samples were collected from 1606 swine farm residents on 40 swine farms in southern China. A total of 1980 pigs' serum samples were collected in the same swine farms where swine workers' serum samples were collected from March 2009 to March 2013. For a control group, 104 serum samples were collected from healthy city residents in Nanchang. All the serum samples were collected to perform hemagglutination inhibition (HI) and (neutralization) NT assays to investigate the prevalence of H5N1 AIV infections in southern China. RESULTS: Sixteen human samples were positive by HI assay and 10 of these were also positive by NT assay against H5N1. No serum samples from human control and pigs were HI positive for H5N1 AIV. DISCUSSION: Our results demonstrate minimal transmission H5N1 AIV from birds to pigs in the swine farms studied and the risk of poultry-to-human and poultry-to pig transmission for at least clades 2.3.2 seemed very low. This study provides the first data regarding antibodies against H5N1 AIV in humans and pigs on swine farms in China. The findings of this study can serve as a baseline for additional serologic studies to assess transmission of H5N1 viruses between avian species, pigs and swine workers. PMID- 24231289 TI - Longitudinal change of liver stiffness by transient elestography in chronic hepatitis B patients treated with nucleos(t)ide analogue. AB - BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a non invasive method to assess liver fibrosis. Decline in LSM value has been reported after antiviral treatment (AVT) using nucleos(t)ide analogues (NUCs) in chronic hepatitis B (CHB) patients, however, factors associated with changes in LSM during AVT remains unclear. METHODS: A total of 76 CHB patients who received AVT with NUCs and had serial LSM (median duration: 16 months, range: 12 to 35 months) during AVT were analyzed. Complete virological response (CVR) was defined when hepatitis B virus DNA level was undetectable by real-time PCR assay (< 50 copies/mL). RESULTS: LSM value had significantly decreased after AVT with NUCs [median (quartile): 6.5 (4.7-9.2) to 5.3 (3.9-6.7), P<0.001]. The median change of LSM value/year was -0.8 (range: -9.5~4.9). The annual change of LSM value was associated with baseline total bilirubin levels, HBeAg status and achievement of CVR during follow-up in univariable analysis, and achievement of CVR during follow-up was an only independent factor associated with the annual change of LSM value [beta coefficients (95% confidence interval)=-0.29 (-2.81~-0.26), P=0.02]. The annual LSM change was significantly different between those who achieved and did not achieve CVR (median change: -1.08/year vs. 0.26/year, P<0.01), and more patients with CVR had decrease in LSM value (89% (47/53) vs. 35% (8/23), P<0.01). CONCLUSIONS: A significant decrease in LSM value was observed in CHB patients after AVT with NUCs. Achievement of CVR was significant factor associated with change in LSM value. Achieving CVR might be a key to decrease LSM value during AVT with NUCs. PMID- 24231291 TI - "Candidatus Sonnebornia yantaiensis", a member of candidate division OD1, as intracellular bacteria of the ciliated protist Paramecium bursaria (Ciliophora, Oligohymenophorea). AB - An intracellular bacterium was discovered in an isolate of Paramecium bursaria from a freshwater pond in Yantai, China. The bacteria were abundant and exclusively found in the cytoplasm of the host which, along with the green alga Chlorella, formed a three-partner consortium that could survive in pure water for at least one week. Cloning, sequencing and phylogenetic analysis of the bacterial 16S rRNA gene showed that the bacterium belonged to the uncultured candidate division OD1, which usually forms part of the rare biosphere. Transmission electron microscopy and fluorescence in situ hybridization (FISH) with specific probes showed that the bacteria were usually located close to the perialgal membranes of endosymbiotic Chlorella cells, and occasionally irregularly distributed throughout the host cytoplasm. The name "Candidatus Sonnebornia yantaiensis" gen. nov., sp. nov. is proposed for the new bacterium. A strongly supported monophyletic subclade, OD1-p, which included the new species, was recognized and this study highlights that protists can be important hosts for rare bacterial taxa. PMID- 24231292 TI - Genomic insights into the taxonomic status of the three subspecies of Bacillus subtilis. AB - Bacillus subtilis contains three subspecies, i.e., subspecies subtilis, spizizenii, and inaquosorum. As these subspecies are phenotypically indistinguishable, their differentiation has relied on phylogenetic analysis of multiple protein-coding gene sequences. B. subtilis subsp. inaquosorum is a recently proposed taxon that encompasses strain KCTC 13429(T) and related strains, which were previously classified as members of subspecies spizizenii. However, DNA-DNA hybridization (DDH) values among the three subspecies raised a question as to their independence. Thus, we evaluated the taxonomic status of subspecies inaquosorum using genome-based comparative analysis. In contrast to the previous experimental values of DDH, the inter-genomic relatedness inferred by average nucleotide identity (ANI) values indicated that subspecies inaquosorum and spizizenii were sufficiently different from subspecies subtilis and hence raised the possibility that the former two could be classified as separate species from B. subtilis. The genome-based tree also supported the separation of the two subspecies from B. subtilis. The exclusive presence of a subtilin synthesis system in subspecies spizizenii was a remarkable genetic characteristic that could even distinguish subspecies spizizenii from subspecies inaquosorum in addition to the low ANI values (<95%). Conclusively, the genome-based data obtained in this study demonstrated that subspecies inaquosorum and spizizenii are clearly distinguished from subspecies subtilis, and raises the possibility that these two subspecies could be classified as separate species from B. subtilis. In addition, the low ANI values between subspecies inaquosorum and spizizenii and the exclusive presence of subtilin synthesis genes in subspecies spizizenii also suggest circumscription of these two subspecies at the species level. PMID- 24231293 TI - Treatment of bacillus Calmette-Guerin refractory non-muscle invasive bladder cancer. AB - Treatment options for patients with non-muscle invasive bladder cancer (NMIBC) refractory to intravesical bacillus Calmette-Guerin (BCG) therapy is reviewed in this article based on the recent published literature. Although intravesical BCG is the best bladder sparing treatment option for NMIBC to prevent recurrence and progression, about 1/3 of cases are refractory to this treatment. At this point radical cystectomy is the standard treatment of choice. If this option is not feasible, intravesical chemotherapy with docetaxel or gemcitabine, the combination of BCG and interferon (INF)-a or device-assisted intravesical strategies, such as mitomycin-EMDA or chemohyperthermia are some of the candidates for further treatment. PMID- 24231294 TI - Outpatient urologic surgery office conducted by nursing staff. A process integrated in a total quality strategy. AB - OBJECTIVES: To create an innovative process to care for urological outpatient surgery patients in an outpatient clinic basis conducted by nursing staff. METHODS: Our centre covers a population of 153,266 inhabitants. A differentiated process for urological outpatient surgery patients has been implemented, conducted by nursing staff trained for the attendance of urologic patients ("phimosis","short penile frenulum",and "vasectomy request" sent from Primary Care units). Planning and implementation phases have been carried out. In the control phase, a questionnaire was given after surgical procedures with 9 different items, in order to assess different issues of the process. RESULTS: A total of 224 patients were attended during the study period, and 175 valid questionnaires were collected (78.1%). The procedures performed were circumcision (11.7%), frenuloplasty (14.6%), and vasectomy (73.7%), with a median patient age of 36 years. Satisfaction level was high for all items of the questionnaire, with 98.2% of patients" very satisfied" or "rather satisfied" when asked for the overall quality of attention of the whole process. The lowest scores were obtained in items that assessed delay from the appointment to attendance date (5.1% of patients "little satisfaction or not satisfied"), and the perception of information supplied (2.3% "little satisfaction or not satisfied"). A lower satisfaction score was observed (in the delay from appointment to attendance) in younger patients (p=0.001) and in patients who underwent circumcision (p=0.004). No complaints with regard to this process were collected. No incorrect indications for interventions were observed. CONCLUSIONS: The attendance of urological outpatient surgery patients can be safely and effectively performed by nursing staff trained for the care of urologic patients, without observing a decrease of the level of user satisfaction. Focusing on a process strategy allows the identification of areas for improvement and makes possible total quality management. PMID- 24231295 TI - Perioperative complications and surgical oncology outcomes in an initial study from 84 patients submitted to laparoscopic radical cystectomy. AB - OBJECTIVES: The Gold Standard treatment for a non-metastatic, invasive bladder cancer is an open radical cystoprostatectomy (ORCP). Laparoscopic radical cystoprostatectomy (LRCP) is still an experimental technique in evaluation. We describe our perioperative results defined as surgical and safety oncology variables. METHODS: Every patient who underwent a LRCP between January 2007 and July 2011 in the urology department of the University Public Hospital was evaluated. We perform a descriptive retrospective analysis. RESULTS: We evaluated 84 patients, 72 males and 12 females, with a mean age of 68 (44-79). A Bricker diversion was performed in 80 patients, a Camey II bladder replacement was performed in 3 patients, and a Studer bladder replacement was performed in 1 patient. Seventeen patients (20.23%) presented with previous abdominal surgery, and 6 patients (7.14%) presented a medical history of urological surgery. The mean surgery time was 257.57 minutes (180-420). The mean hospital stay was 11.875 days (standard deviation (SD): 6.28). The onset of tolerance to surgery occurred after 3.7 days (SD: 2.21).The transfusion rate after surgical intervention was 20.2%. The mean number of nodes removed, by means of ilio-obturator lymphadenectomy, was 17 (13-19). There were no intraoperative complications. Early complications (less than 1 month after the intervention) occurred in 28 patients (33.3% ).There were no post-operative deaths. There were late complications (starting one month after the intervention) in 7 patients (8.3% ). CONCLUSIONS: Our study demonstrated that LRCP is safe and reproducible and represents a minimally invasive option for patients with infiltrative bladder cancer. PMID- 24231296 TI - Usefulness of the Memorial Sloan Kettering Cancer Center nomogram in the prognosis of patients treated with radical cystectomy for invasive bladder cancer. AB - OBJECTIVES: To evaluate the usefulness of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for prediction of recurrence probability in our series of patients who have undergone radical cystectomy for bladder cancer. METHODS: 397 patients underwent radical cystectomy for bladder cancer between 1986 and 2005. 165 patients were excluded:21 due to exitus in the immediate postoperative period, 32 due to previous radiation therapy, 6 due to neoadjuvant chemotherapy, 5 due to inability to complete follow-up, 15 that did not undergo lymphadenectomy and 86 who were alive at the time of review with less than 5 years of follow-up. Patients were classified into recurrence risk groups: organ-confined tumors (pT0 2 pN0 ), extra-bladder involvement (pT3-4 pN0) and lymph node involvement (pN+). Survival analysis was performed using the Kaplan-Meier method. Five-year recurrence-free survival by risk groups in our series was compared with the one estimated using the MSKCC nomogram using a ROC curve. RESULTS: We analyzed 232 patients. Follow-up in patients who died of cancer was 25 +/- 25 months. For alive patients and those who died of other causes, follow-up was 120 +/- 39 months. Pathology studies revealed 42.7% organ-confined tumors , 33.2% with extra bladder involvement and 24.1% with lymph node involvement. The five-year recurrence free survival analysis according to the Kaplan-Meier method stratified by risk groups was: pT0-2 76%, pT3-4 51%, pN+ 31%. The probability of recurrence free survival according to the MSKCC nomogram in the same risk groups was: 85% +/ 5%, 62% +/- 10% and 25% +/- 13%, respectively. The area under the ROC curve was 0.795 (95% CI 0.739-0.852) CONCLUSION: In our series, the MSKCC nomogram constitutes a useful tool for predicting 5-year cancer free survival in patients who undergo radical cystectomy. PMID- 24231297 TI - Predictors of success and hospitalization in semi-rigid ureteroscopy for lithiasis as an outpatient procedure. AB - OBJECTIVES: To analyze the outcomes, predictors of success and predictors of need for hospital admission in our series of patients who underwent ureteroscopy (URS) as a major outpatient surgery (MOS) procedure. METHODS: We carried out a retrospective analysis of 402 patients who had undergone semi-rigid URS for ureteral calculi as a MOS procedure in our center between 2004 and 2012. Patients with previous DJ catheter were excluded. We classified the calculi according to their location (lumbar, pelvic, iliac), size (< or> 1cm) and number (single or multiple). Follow-up was done by plain X-ray of the abdomen and ultrasound one month after surgery. The procedure was considered successful when patients were free from the treated calculi or had ureteral fragments < 3 mm one month after surgery. Univariate and multivariate analyses were carried out to identify the factors involved in success and hospitalization not being required. RESULTS: A total of 269 patients were included. The majority of the stones were single (92.2%), <1 cm in size (76.6%), pelvic (62.1%), and left-sided (57.2%). 89.6% of the procedures were performed as MOS and 82.2% were considered to be successful. In the multivariate analysis, left-sided (p<0.001) and pelvic location of the calculi (p=0,01) were found to be independent predictors for the success of the procedure In terms of hospital admission, the only independent predictor was the presence of intraoperative complications ( p=0.006). CONCLUSIONS: Left-sided and pelvic locations were the independent predictors for the success of the URS. A lack of intraoperative complications was the independent predictor for not requiring hospitalisation. PMID- 24231298 TI - Fibrous pseudotumor affecting the tunica vaginalis, epididymis and seminal duct. AB - OBJECTIVE: To report one case of advanced fibrous pseudotumour. METHODS: A 34 year-old patient presented with a painless lump on the right side of the scrotum. Examination revealed a hard tissue thickening attached to the tail and body of the right epididymis. The results of the ultrasound study were not clear and multiple differential diagnosis were considered. The lesion was surgically removed by partial right epididymectomy and resection of the affected tunica vaginalis and ductus deferens for anatomopathological study. RESULTS: The histopathological study revealed an evolved fibrous pseudotumour with bone metaplasia. CONCLUSION: Fibrous pseudotumour is a benign paratesticular lesion that grows slowly and painlessly. It is usually diagnosed by chance or in associated processes such as hydrocele. Differential diagnosis with malignant tumors avoids unnecessary radical treatment. PMID- 24231299 TI - Hematocele secondary to rupture of an abdominoscrotal hydrocele. AB - OBJECTIVE: To describe one case of hematocele secondary to rupture of an abdominoscrotal hydrocele in an adult patient. METHODS AND RESULTS: We report a huge hematocele in a patient with this unusual type of hydrocele that suffered a minimal scrotal trauma. It was a hydrocele that extended through the inguinal canal to the retroperitoneal space. CONCLUSIONS: Abdominoscrotal hydrocele is a rare condition in children and even rarer in adults. The presence of a hematocele requires early surgical treatment. PMID- 24231300 TI - Urinoma secondary to ureteropelvic junction obstruction in the neonate. Presentation of a case and bibliographic review. AB - OBJECTIVE: To analyze the management of prenatal urinoma and ureteropelvic junction obstruction (UPJO) postnatally by a case report and literature review. METHODS: We report a case of an UPJO and urinoma in a newborn. After birth, renal function was absent, and nephrectomy was performed. The literature from 1985 to date has been reviewed. DISCUSSION: By the analysis of the literature, we can observe mainly, that prenatally diagnosed urinoma and UPJO are managed conservatively. After birth, different attitudes have been carried out, independently of residual renal function, such as radical or reconstructive surgery, or conservative treatment. CONCLUSION: Intrauterine management is not indicated. Urinary diversion is indicated in symptomatic cases secondary to renal trauma or endoscopic procedure. In non-functional kidney, nephrectomy is indicated. PMID- 24231301 TI - Metastasis of gastric carcinoma simulating a urothelial tumor. Case report and review of the literature. AB - OBJECTIVE: To review two cases with the diagnostic suspicion of urinary tract tumor by clinical picture and imaging tests in which pathology of the surgical specimen revealed metastasis of gastric adenocarcinoma. METHODS: 82 and 68 year old patients with past history of gastric adenocarcinoma that had undergone surgical treatment 6 months and 6 years before urology consultation,respectively. They were diagnosed upper urinary tract tumors by CT scan. RESULTS: Definitive pathologic diagnosis of urinary tract metastasis of gastric adenocarcinoma was obtained after radical surgery in both cases. CONCLUSIONS: Clinical and radiologic presentation of urothelial metastases of gastric adenocarcinoma may simulate de novo urothelial tumors. Evolution in these patients is usually bad although we currently don't have enough information to issue a therapeutic guide to follow. PMID- 24231302 TI - Genital self-mutilation. Case report and bibliographic review. AB - OBJECTIVE: To report a very uncommon case of penile open wound made by self mutilation in a 51-year-old man, and to perform a bibliographic review. METHODS: 51-year-old man presenting at the Emergency Department under Police guard after self-cutting his penis while he was urinating, presenting an almost complete circular section that required immediate surgical repair. RESULTS: Early surgical management showed the section of almost the whole penile circumference, from ventral to dorsal, including urethra and both cavernous bodies, respecting only the dorsal vascular penile complex. We performed a primary anastomosis of the damaged structures and careful haemostasis of the penis. CONCLUSIONS: Open traumas to the penis usually require an urgent surgical examination, being mandatory to try a primary reconstruction if the global clinical situation allows it. Cosmetic and functional postoperative results advise this attitude. PMID- 24231303 TI - Polycystic testicle. Case report. AB - Sixty year-old patient without past medical history referring a 6-month history of right testicle pain and simultaneous volume increase. Neither history of sexually transmitted disease nor genital trauma nor obstructive lower urinary tract symptoms were referred during the medical interview. PMID- 24231304 TI - Left renal hypoplasia with ureteral ectopia to the seminal vesicle. PMID- 24231305 TI - Testing which is the fitter position sensor for a cyclotron liquid target. AB - The [(18)F]FDG has 109.7 min half-life, there is a period about 6 h between the beginning of [(18)O]H2O irradiation until the PET-CT exam. Any fail in production chain will result in delay to the PET-CT exam. The absence of the position signs from [(18)O]H2O target valve may result in (18)F production loss. Three types of position sensors were tested. After finding the fitter sensor it was possible to reduce the incidence of fails, increasing the reliability in [(18)F]FDG production chain. PMID- 24231306 TI - Angiogenesis in canine mammary tumours: a morphometric and prognostic study. AB - Angiogenesis in canine mammary tumours (CMTs) has been described previously; however, only the intratumoural (IT) region has been studied and information on peritumoural (PT) angiogenesis is lacking. In this study, the blood vessel density (BVD), blood vessel perimeter (BVP) and blood vessel area (BVA) in IT and PT regions of 56 benign CMTs, 55 malignant CMTs and 13 samples of normal mammary gland tissue were analyzed. In addition, the blood endothelial cell proliferation (BECP) as an indicator of ongoing angiogenesis was investigated. The prognostic value of each parameter was also examined. Blood vessels and proliferating blood endothelial cells were present in IT and PT regions of both benign and malignant tumours. The vessels in the PT region had a significantly higher area and perimeter compared with those in the IT region. Malignant tumours showed significantly more vessels with a smaller total BVA and a higher BECP compared with benign tumours and control tissue. In the PT regions there was a significantly higher BVD, BVA and BVP compared with the vessels in control tissue. Only the IT and PT BVD and PT BECP in benign tumours allowed prediction of survival. The morphology of blood vessels in CMTs shows similarities with those in human breast cancer, which strengthens the case for the use of dogs with CMTs in comparative oncology trials. PMID- 24231307 TI - Second ventilatory threshold from heart-rate variability: valid when the upper body is involved? AB - To determine the most accurate method based on spectral analysis of heart-rate variability (SA-HRV) during an incremental and continuous maximal test involving the upper body, the authors tested 4 different methods to obtain the heart rate (HR) at the second ventilatory threshold (VT(2)). Sixteen ski mountaineers (mean +/- SD; age 25 +/- 3 y, height 177 +/- 8 cm, mass 69 +/- 10 kg) performed a roller-ski test on a treadmill. Respiratory variables and HR were continuously recorded, and the 4 SA-HRV methods were compared with the gas-exchange method through Bland and Altman analyses. The best method was the one based on a time varying spectral analysis with high frequency ranging from 0.15 Hz to a cutoff point relative to the individual's respiratory sinus arrhythmia. The HR values were significantly correlated (r(2) = .903), with a mean HR difference with the respiratory method of 0.1 +/- 3.0 beats/min and low limits of agreements (around 6 /+6 beats/min). The 3 other methods led to larger errors and lower agreements (up to 5 beats/min and around -23/+20 beats/min). It is possible to accurately determine VT(2) with an HR monitor during an incremental test involving the upper body if the appropriate HRV method is used. PMID- 24231308 TI - Fine molecular tuning at position 4 of 2H-chromen-2-one derivatives in the search of potent and selective monoamine oxidase B inhibitors. AB - The effects on the inhibition potencies of monoamine oxidase isoforms A (MAO-A) and B (MAO-B) depending upon changes in the physicochemical properties (size, shape, H-bonding, lipophilicity, etc.) of substituents at the C4 position of 2H chromen-2-one derivatives were extensively investigated, and the results significantly added to our knowledge on this class of MAO inhibitors. All the 67 examined compounds showed high MAO-B selectivity, some of them achieving potency in the low nanomolar range. In particular, the 7-metachlorobenzyloxy-4 oxyacetamido-2H-chromen-2-one (entry 62) showed single digit nanomolar MAO-B potency (IC50 = 3.1 nM) and high selectivity over the MAO-A isoform (selectivity ratio = 7244). The great variety of the investigated substituents at C4 of the 2H chromen-2-one nucleus, combined with binding models generated from docking studies carried out on selected compounds, allowed us to shed light on the main molecular requirements for potent and selective MAO-B inhibition, highlighting the dominant role of the steric effects. Interestingly, many of the designed substituents could be metabolically related to each other (e.g., CH3/CH2OH/CHO/COOH; NH2/NHCH3, NHAc), and therefore the results obtained may help in predicting the in vivo activity of some putative metabolites of lead MAO-B inhibitors. PMID- 24231309 TI - Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. AB - N-(4-(Pyrazol-4-yl)thiazol-2-yl)-N'-phenylthiourea derivative 2 was synthesized and then treated with variety of hydrazonoyl chlorides under basic condition at reflux to afford the corresponding 2-(4-(pyrazol-4-yl)thiazol-2-ylimino)-1,3,4 thiadiazole derivatives 6, 10a-e and 17a-e. Reaction of 2 with ethyl chloroacetate and with 3-chloro-2,4-pentanedione gave the thiazolidin-4-one 22 and 1,3-thiazole 25 derivatives, respectively. Condensation of thiazolidin-4-one 22 with aldehydes gave their 5-arylidene derivatives 23a-f. Most of the synthesized compounds were tested for anticancer activity against human hepatocelluar carcinoma HepG2, human breast cancer MCF-7 and human lung cancer A549. Their SAR was studied and variously affected by the electronic factor of electron donating and withdrawing groups. Many of the tested compounds showed moderate to high anticancer activity. PMID- 24231310 TI - Strategies to understand and overcome brain/spinal cord injury. PMID- 24231311 TI - Kidney injury, stem cells and regeneration. AB - PURPOSE OF REVIEW: The review summarizes the most recent advances in stem cell and regenerative approaches to treat kidney injury, and highlights areas of active controversy. Over the past year, a number of findings have been reported that have brought this field much closer to clinical translation. RECENT FINDINGS: Recent progress in regenerative nephrology includes the directed differentiation of embryonic stem cells to kidney fates, understanding the proliferative capacity of tubules after injury, the use of mesenchymal stem cells for kidney disease and tissue engineering approaches to renal replacement. Controversies persist, however, including whether adult epithelial stem cells exist at all, the best therapeutic strategy for the treatment of kidney injury and how to use mesenchymal stem cells optimally for the prevention of acute kidney injury. SUMMARY: Although recent progress in kidney regeneration is very encouraging, current controversies must be resolved before clinical breakthroughs can occur. PMID- 24231313 TI - Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae. AB - Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10 S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. PMID- 24231312 TI - Expanding role of T cells in acute kidney injury. AB - PURPOSE OF REVIEW: Recent advances in T cell biology have shed light on the role of T cell subsets in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to harness our understanding of recent advances in T cell biology in tissue injury and repair and provide a mechanistic insight into the role of T cells in the inflammation of AKI. RECENT FINDINGS: New specific reagents and genetic animal models have led to advances in our understanding of the role of T cell subsets involved in renal injury. Whereas some T cells promote innate renal inflammation and injury, other T cells promote protection and repair. Recent studies illuminated the pathogenic mechanisms of invariant natural killer T (NKT) cells and T helper1-type responses, and the beneficial functions of regulatory T cells and NKT cells are just beginning to be explored. Pharmacologic and cell-based therapies that influence T cell responses to experimental AKI suggest that this is a promising approach to preserve renal function. SUMMARY: The recent insights gained into how T cells modulate renal injury suggest that strategies targeting specific types of T cells, to either inhibit or enhance their activity, may ameliorate renal injury in patients. PMID- 24231314 TI - Removal of 2,4-dichlorophenol using cyclodextrin-ionic liquid polymer as a macroporous material: characterization, adsorption isotherm, kinetic study, thermodynamics. AB - Cyclodextrin-ionic liquid polymer (betaCD-BIMOTs-TDI) was firstly synthesized using functionalized beta-Cyclodextrin (CD) with 1-benzylimidazole (BIM) to form monofunctionalized CD (betaCD-BIMOTs) and was further polymerized using toluene diisocyanate (TDI) linker to form insoluble betaCD-BIMOTs-TDI. SEM characterization result shows that betaCD-BIMOTs-TDI exhibits macropore size while the BET result shows low surface area (1.254 m(2)g(-1)). The unique properties of the ILs allow us to produce materials with different morphologies. The adsorption isotherm and kinetics of 2,4-dichlorophenol (2,4-DCP) onto betaCD BIMOTs-TDI is studied. Freundlich isotherm and pseudo-second order kinetics are found to be the best to represent the data for 2,4-DCP adsorption on the betaCD BIMOTs-TDI. The presence of macropores decreases the mass transfer resistance and increases the adsorption process by reducing the diffusion distance. The change in entropy (DeltaS degrees ) and heat of adsorption (DeltaH degrees ) for 2,4-DCP on betaCD-BIMOTs-TDI were estimated as -55.99 J/Kmol and -18.10 J/mol, respectively. The negative value of Gibbs free energy (DeltaG degrees ) indicates that the adsorption process is thermodynamically feasible, spontaneous and chemically controlled. Finally, the interactions between the cavity of betaCD BIMOTs and 2,4-DCP are investigated and the results shows that the inclusion of the complex formation and pi-pi interaction are the main processes involved in the adsorption process. PMID- 24231315 TI - The comparison of naturally weathered oil and artificially photo-degraded oil at the molecular level by a combination of SARA fractionation and FT-ICR MS. AB - Two sets of oil samples, one obtained from different weathering stages of the M/V Hebei Spirit oil spill site and the other prepared by an in vitro photo degradation experiment, were analyzed and compared at the molecular level by atmospheric pressure photo-ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). For a more detailed comparison at the molecular level, the oil samples were separated into saturate, aromatic, resin, and asphaltene (SARA) fractions before MS analysis. Gravimetric analysis of the SARA fractions revealed a decreased weight percentage of the aromatic fraction and an increased resin fraction in both sets of samples. Molecular-level investigations of the SARA fractions showed a significant reduction in the S1 class in the saturate fraction and increase of S1O1 class compounds with high DBE values in resin fraction. Levels of N1 and N1O1 class compounds resulting in protonated ions (presumably basic nitrogen compounds) increased after degradation compared to compounds generating molecular ions (presumably non-basic nitrogen compounds). This study revealed changes occurring in heteroatom polar species of crude oils such as sulfur and nitrogen containing compounds that have not been easily detected with conventional GC based techniques. PMID- 24231316 TI - Rapid detection of soils contaminated with heavy metals and oils by laser induced breakdown spectroscopy (LIBS). AB - A laser induced breakdown spectroscopy (LIBS) coupled with the chemometric method was applied to rapidly discriminate between soils contaminated with heavy metals or oils and clean soils. The effects of the water contents and grain sizes of soil samples on LIBS emissions were also investigated. The LIBS emission lines decreased by 59-75% when the water content increased from 1.2% to 7.8%, and soil samples with a grain size of 75 MUm displayed higher LIBS emission lines with lower relative standard deviations than those with a 2mm grain size. The water content was found to have a more pronounced effect on the LIBS emission lines than the grain size. Pelletizing and sieving were conducted for all samples collected from abandoned mining areas and military camp to have similar water contents and grain sizes before being analyzed by the LIBS with the chemometric analysis. The data show that three types of soil samples were clearly discerned by using the first three principal components from the spectral data of soil samples. A blind test was conducted with a 100% correction rate for soil samples contaminated with heavy metals and oil residues. PMID- 24231317 TI - Technological process and optimum design of organic materials vacuum pyrolysis and indium chlorinated separation from waste liquid crystal display panels. AB - In this study, a technology process including vacuum pyrolysis and vacuum chlorinated separation was proposed to convert waste liquid crystal display (LCD) panels into useful resources using self-design apparatuses. The suitable pyrolysis temperature and pressure are determined as 300 degrees C and 50 Pa at first. The organic parts of the panels were converted to oil (79.10 wt%) and gas (2.93 wt%). Then the technology of separating indium was optimized by central composite design (CCD) under response surface methodology (RSM). The results indicated the indium recovery ratio was 99.97% when the particle size is less than 0.16 mm, the weight percentage of NH4Cl to glass powder is 50 wt% and temperature is 450 degrees C. The research results show that the organic materials, indium and glass of LCD panel can be recovered during the recovery process efficiently and eco-friendly. PMID- 24231318 TI - Combination of solid phase extraction and dispersive liquid-liquid microextraction for separation/preconcentration of ultra trace amounts of uranium prior to its fiber optic-linear array spectrophotometry determination. AB - A simple and sensitive method for the separation and preconcentration of the ultra trace amounts of uranium and its determination by spectrophotometry was developed. The method is based on the combination of solid phase extraction and dispersive liquid-liquid microextraction. Thus, by passing the sample through the basic alumina column, the uranyl ion and some cations are separated from the sample matrix. The retained uranyl ion along with the cations are eluted with 5 mL of nitric acid (2 mol L(-1)) and after neutralization of the eluent, the extracted uranyl ion is converted to its anionic benzoate complex and is separated from other cations by extraction of its ion pair with malachite green into small volume of chloroform using dispersive liquid-liquid microextraction. The amount of uranium is then determined by the absorption measurement of the extracted ion pair at 621 nm using flow injection spectrophotometry. Under the optimum conditions, with 500 mL of the sample, a preconcentration factor of 1980, a detection limit of 40 ng L(-1), and a relative standard deviation of 4.1% (n=6) at 400 ng L(-1) were obtained. The method was successfully applied to the determination of uranium in mineral water, river water, well water, spring water and sea water samples. PMID- 24231320 TI - Survival of introduced phosphate-solubilizing bacteria (PSB) and their impact on microbial community structure during the phytoextraction of Cd-contaminated soil. AB - This study was conducted to investigate whether or not phosphate-solubilizing bacteria (PSB) as a kind of plant growth promoting rhizobacteria enhance the uptake of Cd by plants. In addition, the effect of PSB augmentation during phytoextraction on the microbial community of indigenous soil bacteria was also studied. In the initial Cd-contaminated soil, the major phyla were Proteobacteria (35%), Actinobacteria (38%) and Firmicutes (8%). While Proteobacteria were dominant at the second and sixth week (41 and 54%, respectively) in inoculated soil, Firmicutes (mainly belonging to the Bacilli class-61%), dramatically increased in the eight-week soil. For the uninoculated soil, the proportion of alpha-Proteobacteria increased after eight weeks (32%). Interestingly, Actinobacteria class, which was originally present in the soil (37%), seemed to disappear during phytoremediation, irrespective of whether PSB was inoculated or not. Cluster analysis and Principal Component Analysis revealed that the microbial community of eight-week inoculated soil was completely separated from the other soil samples, due to the dramatic increase of Bacillus aryabhattai. These findings revealed that it took at least eight weeks for the inoculated Bacillus sp. to functionally adapt to the introduced soil, against competition with indigenous microorganisms in soil. An ecological understanding of interaction among augmented bacteria, plant and indigenous soil bacteria is needed, for proper management of phytoextraction. PMID- 24231319 TI - Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars. AB - Chemically activated biochar produced under oxygenated (O-biochar) and oxygen free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 alpha ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0-45 ppm), methoxyl (45-63 ppm), O-alkyl (63-108 ppm), and carboxyl carbon (165-187 ppm) content than other adsorbents, while aromaticity of O biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (Kow) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of adsorbates steadily throughout the study. PMID- 24231321 TI - Use of a Monte Carlo technique to complete a fragmented set of H2S emission rates from a wastewater treatment plant. AB - The impact of ambient concentrations in the vicinity of a plant can only be assessed if the emission rate is known. In this study, based on measurements of ambient H2S concentrations and meteorological parameters, the a priori unknown emission rates of a tannery wastewater treatment plant are calculated by an inverse dispersion technique. The calculations are determined using the Gaussian Austrian regulatory dispersion model. Following this method, emission data can be obtained, though only for a measurement station that is positioned such that the wind direction at the measurement station is leeward of the plant. Using the inverse transform sampling, which is a Monte Carlo technique, the dataset can also be completed for those wind directions for which no ambient concentration measurements are available. For the model validation, the measured ambient concentrations are compared with the calculated ambient concentrations obtained from the synthetic emission data of the Monte Carlo model. The cumulative frequency distribution of this new dataset agrees well with the empirical data. This inverse transform sampling method is thus a useful supplement for calculating emission rates using the inverse dispersion technique. PMID- 24231322 TI - Uptake of zwitterionic antibiotics by rice (Oryza sativa L.) in contaminated soil. AB - Antibiotics, including members of the tetracycline and fluoroquinolone families, are emerging organic environmental contaminants. Uptake from soil by plants is a means for antibiotics to enter terrestrial food chains. Chemical exchange between plant and the soil/water matrix occurs simultaneously with degradation in the soil/water matrix. In this study, the comparative temporal behaviour of rice (Oryza sativa L.) towards the zwitterionic antibiotics oxytetracycline, chlortetracycline and norfloxacin at initial soil/water concentrations of 10, 20 and 30 MUg g(-1) (dry weight) is investigated. This is accomplished within the framework of an activity-based mass-conserving dynamic model. Plant antibiotic concentrations are observed to increase to a maximum then decline. Maximum concentrations in rice are compound-dependent linear functions of initial soil/water concentrations, but the relationships are not related to the compound octan-1-ol/water distribution ratio (DOW). The times required to attain maximal concentrations are independent of initial soil/water levels for a given antibiotic, but again vary between antibiotics and are not related to DOW values. Translocation from root to other tissues is not observed. The magnitudes of Root Concentration Factors (RCFs), the ratio of root and soil/water concentrations, are consistent with significant sorption to soil and consequent relatively low concentrations in interstitial water. PMID- 24231323 TI - Scoping candidate minerals for stabilization of arsenic-bearing solid residuals. AB - Arsenic Crystallization Technology (ACT) is a potentially eco-friendly, effective technology for stabilization of arsenic-bearing solid residuals (ABSRs). The strategy is to convert ABSRs generated by water treatment facilities into minerals with a high arsenic capacity and long-term stability in mature, municipal solid waste landfills. Candidate minerals considered in this study include scorodite, arsenate hydroxyapatites, ferrous arsenates (symplesite-type minerals), tooeleite, and arsenated-schwertmannite. These minerals were evaluated as to ease of synthesis, applicability to use of iron-based ABSRs as a starting material, and arsenic leachability. The Toxicity Characteristic Leaching Procedure (TCLP) was used for preliminary assessment of candidate mineral leaching. Minerals that passed the TCLP and whose synthesis route was promising were subjected to a more aggressive leaching test using a simulated landfill leachate (SLL) solution. Scorodite and arsenate hydroxyapatites were not considered further because their synthesis conditions were not found to be favorable for general application. Tooeleite and silica-amended tooeleite showed high TCLP arsenic leaching and were also not investigated further. The synthesis process and leaching of ferrous arsenate and arsenated-schwertmannite were promising and of these, arsenated-schwertmannite was most stable during SLL testing. The latter two candidate minerals warrant synthesis optimization and more extensive testing. PMID- 24231324 TI - Citric acid modifies surface properties of commercial CeO2 nanoparticles reducing their toxicity and cerium uptake in radish (Raphanus sativus) seedlings. AB - Little is known about the mobility, reactivity, and toxicity to plants of coated engineered nanoparticles (ENPs). Surface modification may change the interaction of ENPs with living organisms. This report describes surface changes in commercial CeO2 NPs coated with citric acid (CA) at molar ratios of 1:2, 1:3, 1:7, and 1:10 CeO2:CA, and their effects on radish (Raphanus sativus) seed germination, cerium and nutrients uptake. All CeO2 NPs and their absorption by radish plants were characterized by TEM, DLS, and ICP-OES. Radish seeds were germinated in pristine and CA coated CeO2 NPs suspensions at 50mg/L, 100mg/L, and 200mg/L. Deionized water and CA at 100mg/L were used as controls. Results showed zeta potential values of 21.6 mV and -56 mV for the pristine and CA coated CeO2 NPs, respectively. TEM images showed denser layers surrounding the CeO2 NPs at higher CA concentrations, as well as better distribution and smaller particle sizes. None of the treatments affected seed germination. However, at 200mg/L the CA coated NPs at 1:7 ratio produced significantly (p <= 0.05) more root biomass, increased water content and reduced by 94% the Ce uptake, compared to bare NPs. This suggests that CA coating decrease CeO2 NPs toxicity to plants. PMID- 24231325 TI - High surface area Ag-TiO2 nanotubes for solar/visible-light photocatalytic degradation of ceftiofur sodium. AB - Titanium dioxide nanotubes (TiO2 NTs) with very high surface area (469 m(2)/g) have been synthesized through a simple hydrothermal method and their surface has been modified using silver nanoparticles (Ag NPs). The Ag NPs deposited TiO2 NTs (Ag-TiO2 NTs) show an extended optical response from UV to visible region coupled with a surface plasmon resonance band and thus can be utilized as a plasmonic photocatalyst. The photoluminescence intensity of TiO2 NTs is lower than that of TiO2 nanoparticles due to the delocalization of photogenerated electrons along the one dimensional nanotubes which reduces the rate of charge recombination. The Langmuir adsorption constant of Ag-TiO2 NTs (for ceftiofur sodium adsorption) is twice that of P25 TiO2. The Ag-TiO2 NTs exhibit excellent photocatalytic activity toward the degradation of ceftiofur sodium (CFS) due to high surface area and mesoporosity of TiO2 NTs. The addition of peroxomonosulfate in the photocatalytic system greatly amplifies the CFS degradation owing to the simultaneous generation of both OH and SO4(-). The catalyst retains its photocatalytic activity at least up to four consecutive cycles. PMID- 24231326 TI - A new insight on the core-shell structure of zerovalent iron nanoparticles and its application for Pb(II) sequestration. AB - Nanoscale zerovalent iron (nZVI) has shown a high efficacy for removing heavy metals from liquid solution. However, its removal capacity has not been fully explored due to its common shell composition (FeOOH). In this study, a much higher removal capacity of Pb(II) is observed (1667 mg Pb(II)/gFe), which is over 100% higher than the highest removal capacity of nZVI reported before. High resolution X-ray photoelectron spectroscopy (HR-XPS) reveals that through restricting the dehydration process of Fe(OH)3, nZVI can acquire a unique shell, which is composed of 45.5% Fe(OH)3 and 54.5% FeOOH. The presence of Fe(OH)3 suppresses the reduction of Pb(II), but greatly promotes the co-precipitation and adsorption of Pb(II). Combining the ratio of Fe-released to Pb-immobilized and the result of HR-XPS, a reaction between Fe(0) core, Fe(OH)3, and Pb(II) is proposed. The Fe released from the Fe(0) core leads to the core depletion, observed by transmission electron microscopy (TEM) under high Pb(II) loading. While temperature has little influence on the removal capacity, pH affects the removal capacity greatly. pH<4.5 favors Fe dissolution, while pH>4.5 promotes Pb(II) adsorption. Given the high Pb removal capacity via the Fe(OH)3 shell, nZVI can be used to remedy Pb(II) contamination. PMID- 24231327 TI - Risk assessments of PAHs and Hg exposure via settled house dust and street dust, linking with their correlations in human hair. AB - Domestic energy, chemicals bioaccessibility and particle size were found as three critical factors for risk assessment of PAHs exposure via settled house dust (SHD) and street dust. ?PAHs and Hg contained in SHD were significantly (p<0.01) higher in coal-burning households of Qingyang (8.45-121; 0.48-16.4 MUg g(-1)) than households in Guangzhou (1.23-22.2; 0.004-10.6 MUg g(-1)) and 90% coal burning houses were estimated with unacceptable cancer risks (>10(-4)) via SHD exposure. The highest accumulation trend of PAHs and Hg were found in <63 MUm particles, and different particle sizes resulted in large variations of the obtained risks (up to 10 fold). Bioaccessibility corrected PAHs led to a significant decrease on related cancer risks and decreased in the order of 1.9, 1.1, 0.6 and 0.4 MUg g(-1) with the increase of particle sizes (<63, 63-100, 100 280, 280-2000 MUm). Scalp hair was tested as an indicator of body burdens of PAHs (0.05-0.9 MUg g(-1)) and Hg (0.04-1.6 MUg g(-1)). Different PAHs profiles were found between PAHs in SHD and those of hair, indicating that exogenous exposure to PAHs adsorbed on dust was not the major source of hair PAHs. PMID- 24231328 TI - Targeting ribonucleic acids by toxic small molecules: structural perturbation and energetics of interaction of phenothiazinium dyes thionine and toluidine blue O to tRNA phe. AB - This study was designed to examine the toxic interaction of two phenothiazinium dyes thionine (TO) and toluidine blue O (TBO) with tRNA(phe) by spectroscopic and calorimetric techniques. While phenothiazinium dye complexation with DNA is known, their bindings to RNA are not fully investigated. The non cooperative binding of both the dyes to tRNA was revealed from absorbance and fluorescence studies. From absorption, steady-state emission, the effect of ferrocyanide ion induced steady-state fluorescence quenching, circular dichroism, the mode of binding of these dyes into the tRNA helix has been substantiated to be principally by intercalative in nature. Both dyes enhanced the thermal stability of tRNA. Circular dichroism studies provided evidence for the structural perturbations associated with the tRNA structure with induction of optical activity in the CD inactive dye molecules. Results from isothermal titration calorimetry experiments suggested that the binding of both dyes was predominantly entropy driven with a smaller but favorable enthalpy term that increased with temperature. The binding was dependent on the Na(+) concentration, but had a larger non-electrostatic contribution to the Gibbs energy. A small heat capacity value and the enthalpy-entropy compensation in the energetics of the interaction characterized the binding of the dyes to tRNA. This study confirms that the tRNA(phe) binding affinity is greater for TO compared to TBO. The utility of the present work lies in understanding the potential binding and consequent damage to tRNA by these toxic dyes in their development as therapeutic agents. PMID- 24231329 TI - Influence of Fenton's reagent doses on the degradation and mineralization of H acid. AB - The recalcitrant H-acid (1-amino-8-naphthol-3,6-disulfonic acid) in aqueous solution was oxidized by Fenton process, focusing on the relation of Fenton's reagent doses and degradation products. The experimental results showed that COD and TOC removals and biodegradability (BOD/COD ratio) of the solution increased with increasing Fenton's reagent doses. Over 80% COD can be removed and the biodegradability was improved significantly. It was found that major SO3H and NH2 groups in H-acid molecules were mineralized to SO4(2-) and NH4(+) ions during Fenton oxidation processes. H-acid degradation intermediates with benzene structures substituted by hydroxyl and/or carboxyl groups were identified by GC MS. It was also found that short-chain fatty acids primarily oxalic acid were degradation products of H-acid by Fenton oxidation. Oxalic acid accumulated could account for approximately 60% of the residual TOC. The degradation pathway of H acid was proposed based on above analyses in this work. PMID- 24231330 TI - Degradation of simazine from aqueous solutions by diatomite-supported nanosized zero-valent iron composite materials. AB - A novel composite material based on deposition of nanosized zero-valent iron (nZVI) particles on acid-leached diatomite was synthesised for the removal of a chlorinated contaminant in water. The nZVI/diatomite composites were characterised by X-ray diffraction, scanning electron microscopy, elemental analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. Compared with the pure nZVI particles, better dispersion of nZVI particles on the surface or inside the pores of diatom shells was observed. The herbicide simazine was selected as the model chlorinated contaminant and the removal efficiency by nZVI/diatomite composite was compared with that of the pristine nZVI and commercial iron powder. It was found that the diatomite supported nZVI composite material prepared by centrifugation exhibits relatively better efficient activity in decomposition of simazine than commercial Fe, lab synthesised nZVI and composite material prepared via rotary evaporation, and the optimum experimental conditions were obtained based on a series of batch experiments. This study on immobilising nZVI particles onto diatomite opens a new avenue for the practical application of nZVI and the diatomite-supported nanosized zero-valent iron composite materials have potential applications in environmental remediation. PMID- 24231331 TI - Evaluating the interactions of organic compounds with multi-walled carbon nanotubes by self-packed HPLC column and linear solvation energy relationship. AB - Understanding the interactions between organic pollutants and carbon nanotubes (CNTs) is critical for fate assessment of both CNTs and organic pollutants. In this study, the chromatographic approach was introduced based on CNTs as stationary phase for the evaluation of such interactions. The pristine multi walled carbon nanotubes (MWCNTs) were packed into columns of high-pressure liquid chromatography (HPLC) and the retention factors (k') were determined to characterize the adsorption affinity of organic compounds onto MWCNTs. Nine compounds were tested. The results showed that their lnk' values followed the order: benzene < toluene < phenol < chlorobenzene < bromobenzene < aniline < sulfamethoxazole < sulfadiazine ~ sulfadimidine. The linear solvation energy relationship (LSER) theory was adopted to correlate lnk' with the molecular solvatochromic parameters. We found that lnk' of the studied compounds correlate positively with molecular polarizability (E) significantly, suggesting that the pi-/n-electrons-dependent polarizable interactions play a major role for the adsorption. Moreover, the thermodynamic parameters calculated from van't Hoff equations revealed that the interactions between the compounds and MWCNTs were spontaneous and exothermic processes. PMID- 24231332 TI - Efficient removal of endosulfan from aqueous solution by UV-C/peroxides: a comparative study. AB - This study explored the efficiency of UV-C-based advanced oxidation processes (AOPs), i.e., UV/S2O8(2-), UV/HSO5(-), and UV/H2O2 for the degradation of endosulfan, an organochlorine insecticide and an emerging water pollutant. A significant removal, 91%, 86%, and 64%, of endosulfan, at an initial concentration of 2.45 MUM and UV fluence of 480 mJ/cm(2), was achieved by UV/S2O8(2-), UV/HSO5(-), and UV/H2O2 processes, respectively, at a [peroxide]0/[endosulfan]0 molar ratio of 20. The efficiency of these processes was, however, inhibited in the presence of radical scavengers, such as alcohols (e.g., tertiary butyl alcohol and isopropyl alcohol) and natural organic matter (NOM). The inhibition was also influenced by common inorganic anions in the order of nitrite > bicarbonate > chloride > nitrate ~ sulfate. The observed pseudo first-order rate constant decreased while the degradation rate increased with increasing initial concentration of the target contaminant. The degradation mechanism of endosulfan by the AOPs was evaluated revealing the main by-product as endosulfan ether. Results of this study suggest that UV-C-based AOPs are potential methods for the removal of pesticides, such as endosulfan and its by products, from contaminated water. PMID- 24231333 TI - Removal of chromium ions from wastewater by duckweed, Lemna minor L. by using a pilot system with continuous flow. AB - The aim of this study was to determine the ability of Lemna minor to remove Cr (VI) ions from wastewater in a continuous flow pond system. This system was used to simulate a wastewater treatment pond and a natural wetland as habitat of plants. In order to find optimal conditions for chromium removal, ponds were operated with aqueous solutions having different pH (4.0-7.0) and chromium concentration of 0.25 mgCr(+6)/L, then plants were exposed to different chromium concentrations (0.25-5.0 mgCr(+6)/L) at pH 4.0. Chromium concentrations, both in biomass and wastewater, were measured and removal efficiency was determined throughout water flow. Growth factors such as growth rates, chlorophyll contents and dry/fresh weight ratios of plants were also determined to measure toxic effects of chromium. The percentages of chromium uptake (PMU) and bioconcentration factors (BCF) were calculated for each run. The highest accumulated chromium concentration (4.423 mgCr/g) was found in plants grown in the first chamber of pond operated at pH 4.0 and 5.0 mgCr/L, while the minimum accumulated chromium concentration (0.122 mgCr/g) was in plants grown in the last chamber of pond operated at pH 4.0 and 0.25 mgCr(+6)/L. PMID- 24231334 TI - Molecular interactions of benzophenone UV filters with human serum albumin revealed by spectroscopic techniques and molecular modeling. AB - Benzophenone (BP)-type UV filters have been widely used in many personal care products to protect human from UV exposure. Their dermal applications can cause direct human health risk following accumulation in bloodstream. Few studies have addressed whether BP-type UV filters could bind and alter the structure and function of human serum albumin (HSA), the major carrier protein in plasma. Four benzophenones, BP-1, BP-2, BP-3 and BP-8 were selected to investigate their potentially toxic interactions with HSA and the intrinsic binding mechanism using combined spectroscopies and molecular docking techniques. Four benzophenones significantly quench the intrinsic fluorescence of HSA via static mode. The competitive binding fluorescence assay and molecular docking both revealed that the benzophenones bind at site II of HSA. Their binding constants range from 1.91 * 10(4)M(-1) to 12.96 * 10(4)M(-1) at 296 K. BP-8 interacts with HSA mainly through hydrogen bonding interactions and van der Waals interactions, while hydrophobic interactions and electrostatic interactions are dominant for interactions between BP-1, BP-2, BP-3 and HSA. Molecular docking revealed that the changes in structural moiety and hydrophobicity of four benzophenones account for their different binding affinities. As further revealed by circular dichroism and time-resolved fluorescence decay, these benzophenones cause global and local structural changes of HSA, which illustrates their potential toxicity to cause structural damage of HSA. Two degradation products of BP-3 have higher binding affinities to HSA, suggesting higher potencies in causing adverse effects on human health. PMID- 24231335 TI - Toxicity of binary mixtures of oil fractions to sea urchin embryos. AB - The assumption of additive toxicity for oil compounds is related to a narcotic mode of action. However, the joint toxicity of oil fractions has not been fully investigated. A fractionation of Maya crude oil into aliphatics, aromatics and polars was performed, fractions were dissolved in dimethyl sulfoxide (DMSO) and subsequently toxicity of single fractions and binary mixtures was assessed using the sea urchin embryo test. The descriptive ability of Concentration Addition (CA), Independent Action (IA) and modifications of both models for describing the joint toxicity of mixtures has also been evaluated. The hydrocarbon content extractable with dichloromethane of the fractions dissolved in DMSO was: 12.0 +/- 1.8 mg mL(-1), 39.0 +/- 0.5 mg mL(-1) and 20.5 +/- 2.5 mg mL(-1) for aliphatics, aromatics and polars, respectively. The toxicity of the extracts in DMSO of the fractions as EC50 (MULL(-1)) was: aliphatics (165.8-242.3)30%). Perfusion imaging (CT or MRI) for other head and neck tumors is currently being developed and is being assessed. It should be a tool to assist in choosing the most appropriate initial treatment (chemotherapy, radiotherapy or surgery) and should also allow poor responders to conservative treatment to be identified and recurrences to be detected in post treatment damaged tissues. AIMS: (a) to determine when to perform perfusion MRI; (b) to determine the type of perfusion to carry out: CT, T1-weighted MRI; (c) to determine how to position the region of interest to plot the perfusion curve; (d) to know how to interpret MRI curves for salivary gland tumors; (e) to know how to interpret the information obtained from perfusion CT or MRI for the upper aerodigestive tract. PMID- 24231346 TI - Medico-economic study of the management of hepatocellular carcinoma by chemo embolization. AB - PURPOSE: This study has two aims. The first is to compare conventional lipiodol chemo-embolization (Trans Arterial Chemo-Embolization - TACE) to one using pre loaded particles (Trans Arterial Chemo-Embolisation-Drug Eluted Bead - TACE-DEB) using a cost minimization study. The second is to define the fundable nature of TACE-DEB and the conditions under which it is cost-effective. MATERIALS AND METHODS: Retrospective study of patients treated by chemo-embolization (n=31: TACE; n=32: TACE-DEB) during the year 2010. The cost minimization study was conducted from the hospital perspective. Direct medical costs were calculated and compared using the readjusted ENCC (National Studies of Costs by Common Methodology) method. The affordability of the two techniques and definition of a cost-effective hypothesis (break-even point) were also established. RESULTS: All DRGs combined, lengths of stay (TACE: 4.90 +/- 3.36; TACE-DEB: 5.03 +/- 3.36) does not change significantly. An average upper mean cost for TACE-DEB is described (TACE: 2869.05 ?; TACE-DEB: 3960.10 ?). The affordability calculations in the study show that, overall, TACE-DEB can be funded regardless of DRG. A ratio of 1.3 procedures using the conventional (TACE) method would enable TACE DEB procedures to be funded. CONCLUSION: This medico-economic analysis demonstrates that the TACE-DEB procedure is fundable. PMID- 24231347 TI - ArhGEF18 regulated Rho signaling in vertebrate retina development. AB - Epithelia consisting of highly polarized columnar cells contribute to many organs during development, including the central nervous system. Epithelial organization is essential for proliferation and differentiation of progenitor cells and subsequent organ morphology and function. Small GTPases of the Rho family are important regulators of cellular morphology and polarity. We recently identified ArhGEF18 as a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium. ArhGEF18 is required to maintain apico-basal polarity, localization of tight junctions and cortical actin, thus shaping cellular morphology. Loss of ArhGEF18 activity results in increased proliferation and reduced cell cycle exit. Together, these perturbations result in a severely misshaped embryonic eye, where the stereotype arrangement of retinal cell types is randomized. Our findings reveal an important role for RhoA-Rock2 signaling to maintain apico-basal polarity in retinal progenitor cells, which is essential for subsequent cellular differentiation, morphology and eventually organ function. PMID- 24231348 TI - High resolution diffusion weighted magnetic resonance imaging of the pancreas using reduced field of view single-shot echo-planar imaging at 3 T. AB - Diffusion weighted magnetic resonance imaging (DWI) has been mostly acquired using single-shot echo-planar imaging (ss EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in ss EPI especially for abdominal imaging, even with the advances in parallel imaging. A novel method of reduced Field of View ss EPI (rFOV ss EPI) has achieved high resolution DWI in human carotid artery, spinal cord with reduced blurring and higher spatial resolution than conventional ss EPI, but it has not been used to pancreas imaging. In the work, comparisons between the full FOV ss-DW EPI and rFOV ss-DW EPI in image qualities and ADC values of pancreatic tumors and normal pancreatic tissues were performed to demonstrate the feasibility of pancreatic high resolution rFOV DWI. There were no significant differences in the mean ADC values between full FOV DWI and rFOV DWI for the 17 subjects using b=600s/mm(2) (P=0.962). However, subjective scores of image quality was significantly higher at rFOV ss DWI (P=0.008 and 0.000 for b-value=0s/mm(2) and 600s/mm(2) respectively). The spatial resolution of DWI for pancreas was increased by a factor of over 2.0 (from almost 3.0mm/pixel to 1.25mm/pixel) using rFOV ss EPI technique. Reduced FOV ss EPI can provide good DW images and is promising to benefit applications for pancreatic diseases. PMID- 24231349 TI - Balancing GRK2 and EPAC1 levels prevents and relieves chronic pain. AB - Chronic pain is a major clinical problem, yet the mechanisms underlying the transition from acute to chronic pain remain poorly understood. In mice, reduced expression of GPCR kinase 2 (GRK2) in nociceptors promotes cAMP signaling to the guanine nucleotide exchange factor EPAC1 and prolongs the PGE2-induced increase in pain sensitivity (hyperalgesia). Here we hypothesized that reduction of GRK2 or increased EPAC1 in dorsal root ganglion (DRG) neurons would promote the transition to chronic pain. We used 2 mouse models of hyperalgesic priming in which the transition from acute to chronic PGE2-induced hyperalgesia occurs. Hyperalgesic priming with carrageenan induced a sustained decrease in nociceptor GRK2, whereas priming with the PKCepsilon agonist PsiepsilonRACK increased DRG EPAC1. When either GRK2 was increased in vivo by viral-based gene transfer or EPAC1 was decreased in vivo, as was the case for mice heterozygous for Epac1 or mice treated with Epac1 antisense oligodeoxynucleotides, chronic PGE2-induced hyperalgesia development was prevented in the 2 priming models. Using the CFA model of chronic inflammatory pain, we found that increasing GRK2 or decreasing EPAC1 inhibited chronic hyperalgesia. Our data suggest that therapies targeted at balancing nociceptor GRK2 and EPAC1 levels have promise for the prevention and treatment of chronic pain. PMID- 24231350 TI - Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration. AB - A systems pharmacological approach that capitalizes on the characterization of intracellular signaling networks can transform our understanding of human diseases and lead to therapy development. Here, we applied this strategy to identify pharmacological targets for the treatment of Stargardt disease, a severe juvenile form of macular degeneration. Diverse GPCRs have previously been implicated in neuronal cell survival, and crosstalk between GPCR signaling pathways represents an unexplored avenue for pharmacological intervention. We focused on this receptor family for potential therapeutic interventions in macular disease. Complete transcriptomes of mouse and human samples were analyzed to assess the expression of GPCRs in the retina. Focusing on adrenergic (AR) and serotonin (5-HT) receptors, we found that adrenoceptor alpha 2C (Adra2c) and serotonin receptor 2a (Htr2a) were the most highly expressed. Using a mouse model of Stargardt disease, we found that pharmacological interventions that targeted both GPCR signaling pathways and adenylate cyclases (ACs) improved photoreceptor cell survival, preserved photoreceptor function, and attenuated the accumulation of pathological fluorescent deposits in the retina. These findings demonstrate a strategy for the identification of new drug candidates and FDA-approved drugs for the treatment of monogenic and complex diseases. PMID- 24231351 TI - Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. AB - Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type alpha-1 antitrypsin (M-AAT) to AAT deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction of inflammatory cells compared with 3 month biopsies. Deep sequencing of the TCR Vbeta region from muscle biopsies demonstrated a limited number of T cell clones that emerged at 3 months after vector administration and persisted for 1 year. In situ immunophenotyping revealed a substantial Treg population in muscle biopsy samples containing AAT-expressing myofibers. Approximately 10% of all T cells in muscle were natural Tregs, which were activated in response to AAV capsid. These results suggest that i.m. delivery of rAAV type 1-AAT (rAAV1-AAT) induces a T regulatory response that allows ongoing transgene expression and indicates that immunomodulatory treatments may not be necessary for rAAV-mediated gene therapy. PMID- 24231352 TI - p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes. AB - Cellular senescence contributes to aging and decline in tissue function. p53 isoform switching regulates replicative senescence in cultured fibroblasts and is associated with tumor progression. Here, we found that the endogenous p53 isoforms Delta133p53 and p53beta are physiological regulators of proliferation and senescence in human T lymphocytes in vivo. Peripheral blood CD8+ T lymphocytes collected from healthy donors displayed an age-dependent accumulation of senescent cells (CD28-CD57+) with decreased Delta133p53 and increased p53beta expression. Human lung tumor-associated CD8+ T lymphocytes also harbored senescent cells. Cultured CD8+ blood T lymphocytes underwent replicative senescence that was associated with loss of CD28 and Delta133p53 protein. In poorly proliferative, Delta133p53-low CD8+CD28- cells, reconstituted expression of either Delta133p53 or CD28 upregulated endogenous expression of each other, which restored cell proliferation, extended replicative lifespan and rescued senescence phenotypes. Conversely, Delta133p53 knockdown or p53beta overexpression in CD8+CD28+ cells inhibited cell proliferation and induced senescence. This study establishes a role for Delta133p53 and p53beta in regulation of cellular proliferation and senescence in vivo. Furthermore, Delta133p53-induced restoration of cellular replicative potential may lead to a new therapeutic paradigm for treating immunosenescence disorders, including those associated with aging, cancer, autoimmune diseases, and HIV infection. PMID- 24231353 TI - Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression. AB - Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability. PMID- 24231354 TI - Immune response to RB1-regulated senescence limits radiation-induced osteosarcoma formation. AB - Ionizing radiation (IR) and germline mutations in the retinoblastoma tumor suppressor gene (RB1) are the strongest risk factors for developing osteosarcoma. Recapitulating the human predisposition, we found that Rb1+/- mice exhibited accelerated development of IR-induced osteosarcoma, with a latency of 39 weeks. Initial exposure of osteoblasts to carcinogenic doses of IR in vitro and in vivo induced RB1-dependent senescence and the expression of a panel of proteins known as senescence-associated secretory phenotype (SASP), dominated by IL-6. RB1 expression closely correlated with that of the SASP cassette in human osteosarcomas, and low expression of both RB1 and the SASP genes was associated with poor prognosis. In vivo, IL-6 was required for IR-induced senescence, which elicited NKT cell infiltration and a host inflammatory response. Mice lacking IL 6 or NKT cells had accelerated development of IR-induced osteosarcomas. These data elucidate an important link between senescence, which is a cell-autonomous tumor suppressor response, and the activation of host-dependent cancer immunosurveillance. Our findings indicate that overcoming the immune response to senescence is a rate-limiting step in the formation of IR-induced osteosarcoma. PMID- 24231355 TI - Topical hypochlorite ameliorates NF-kappaB-mediated skin diseases in mice. AB - Nuclear factor-kappaB (NF-kappaB) regulates cellular responses to inflammation and aging, and alterations in NF-kappaB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-kappaB dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-kappaB kinase (IKK), a key regulator of NF-kappaB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-kappaB reporter mice, topical HOCl reduced LPS-induced NF-kappaB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-kappaB-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-kappaB dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-kappaB mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims. PMID- 24231356 TI - Inhibition of mitochondrial fragmentation diminishes Huntington's disease associated neurodegeneration. AB - Huntington's disease (HD) is the result of expression of a mutated Huntingtin protein (mtHtt), and is associated with a variety of cellular dysfunctions including excessive mitochondrial fission. Here, we tested whether inhibition of excessive mitochondrial fission prevents mtHtt-induced pathology. We developed a selective inhibitor (P110-TAT) of the mitochondrial fission protein dynamin related protein 1 (DRP1). We found that P110-TAT inhibited mtHtt-induced excessive mitochondrial fragmentation, improved mitochondrial function, and increased cell viability in HD cell culture models. P110-TAT treatment of fibroblasts from patients with HD and patients with HD with iPS cell-derived neurons reduced mitochondrial fragmentation and corrected mitochondrial dysfunction. P110-TAT treatment also reduced the extent of neurite shortening and cell death in iPS cell-derived neurons in patients with HD. Moreover, treatment of HD transgenic mice with P110-TAT reduced mitochondrial dysfunction, motor deficits, neuropathology, and mortality. We found that p53, a stress gene involved in HD pathogenesis, binds to DRP1 and mediates DRP1-induced mitochondrial and neuronal damage. Furthermore, P110-TAT treatment suppressed mtHtt-induced association of p53 with mitochondria in multiple HD models. These data indicate that inhibition of DRP1-dependent excessive mitochondrial fission with a P110-TAT-like inhibitor may prevent or slow the progression of HD. PMID- 24231357 TI - Inhibition of the TRPC5 ion channel protects the kidney filter. AB - An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca2+-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease. PMID- 24231359 TI - Marked genomic heterogeneity of rat hepatitis E virus strains in Indonesia demonstrated on a full-length genome analysis. AB - Rat hepatitis E virus (HEV) strains have recently been isolated in several areas of Germany, Vietnam, the United States, Indonesia and China. However, genetic information regarding these rat HEV strains is limited. A total of 369 wild rats (Rattus rattus) captured in Central Java (Solo) and on Lombok Island, Indonesia were tested for the presence of rat HEV-specific antibodies and RNA. Overall, 137 rats (37.1%) tested positive for rat anti-HEV antibodies, while 97 (26.3%) had rat HEV RNA detectable on reverse transcription-PCR with primers targeting the ORF1-ORF2 junctional region. The 97 HEV strains recovered from these viremic rats were 76.3-100% identical to each other in an 840-nucleotide sequence and 75.4 88.4% identical to the rat HEV strains reported in Germany and Vietnam. Five representative Indonesian strains, one from each of five phylogenetic clusters, whose entire genomic sequence was determined, were segregated into three genetic groups (a German type, Vietnamese type and novel type), which differed from each other by 19.5-23.5 (22.0 +/- 1.7)% over the entire genome. These results suggest the presence of at least three genetic groups of rat HEV and indicate the circulation of polyphyletic strains of rat HEV belonging to three distinct genetic groups in Indonesia. PMID- 24231358 TI - Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks. AB - The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with MUPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID- 24231360 TI - Comparison of athlete-coach perceptions of internal and external load markers for elite junior tennis training. AB - PURPOSE: To investigate the discrepancy between coach and athlete perceptions of internal load and notational analysis of external load in elite junior tennis. METHODS: Fourteen elite junior tennis players and 6 international coaches were recruited. Ratings of perceived exertion (RPEs) were recorded for individual drills and whole sessions, along with a rating of mental exertion, coach rating of intended session exertion, and athlete heart rate (HR). Furthermore, total stroke count and unforced-error count were notated using video coding after each session, alongside coach and athlete estimations of shots and errors made. Finally, regression analyses explained the variance in the criterion variables of athlete and coach RPE. RESULTS: Repeated-measures analyses of variance and interclass correlation coefficients revealed that coaches significantly (P < .01) underestimated athlete session RPE, with only moderate correlation (r = .59) demonstrated between coach and athlete. However, athlete drill RPE (P = .14; r = .71) and mental exertion (P = .44; r = .68) were comparable and substantially correlated. No significant differences in estimated stroke count were evident between athlete and coach (P = .21), athlete notational analysis (P = .06), or coach notational analysis (P = .49). Coaches estimated significantly greater unforced errors than either athletes or notational analysis (P < .01). Regression analyses found that 54.5% of variance in coach RPE was explained by intended session exertion and coach drill RPE, while drill RPE and peak HR explained 45.3% of the variance in athlete session RPE. CONCLUSION: Coaches misinterpreted session RPE but not drill RPE, while inaccurately monitoring error counts. Improved understanding of external- and internal-load monitoring may help coach athlete relationships in individual sports like tennis avoid maladaptive training. PMID- 24231361 TI - Detection of hepatitis C virus by single-step hairpin primer RT-PCR. AB - We developed a novel single-step virus detection system using the fluorescent molecule with a hairpin primer on the reverse transcription (RT)-polymerase chain reaction (PCR). Primers that are specific to Hepatitis C virus (HCV) having a hairpin tag at the 5'-end were used for RT and PCR. The HCV-RNA template was reverse transcribed by reverse transcriptase with the hairpin primer (HP), and the resulting cDNA was amplified directly by HP-PCR (RT-HP-PCR). Using the RT-HP PCR, we succeeded in demonstrating the detection of HCV-RNA in single-step. The RT-HP-PCR selectively detected HCV-RNA extracted from patients' sera containing contaminant materials. The method could be applicable to the quantitative detection of HCV. PMID- 24231362 TI - Discovery of benzo[d]imidazo[5,1-b]thiazole as a new class of phosphodiesterase 10A inhibitors. AB - The design, synthesis and structure activity relationship studies of a series of compounds from benzo[d]imidazo[5,1-b]thiazole scaffold as phosphodiesterase 10A (PDE10A) inhibitors are discussed. Several potent analogs with heteroaromatic substitutions (9a-d) were identified. The anticipated binding mode of these analogs was confirmed by performing the in silico docking experiments. Later, the heteroaromatics were substituted with saturated heteroalkyl groups which provided a tool compound 9e with excellent PDE10A activity, PDE selectivity, CNS penetrability and with favorable pharmacokinetic profile in rats. Furthermore, the compound 9e was shown to be efficacious in the MK-801 induced psychosis model and in the CAR model of psychosis. PMID- 24231363 TI - DPMA, a deoxypodophyllotoxin derivative, induces apoptosis and anti-angiogenesis in non-small cell lung cancer A549 cells. AB - We found that the deoxypodophyllotoxin derivative, 2,6-dimethoxy-4-(6-oxo (5R,5aR,6,8,8aR,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)phenyl ((R)-1-amino-4-(methylthio)-1-oxobutan-2-yl)carbamate (DPMA), exhibited superior cytotoxicity compared with etoposide. In this study, we investigated the mechanism of action of DPMA. DPMA exhibited anti-proliferative activity and induced apoptosis in A549 cells in a dose- and time-dependant manner. DPMA inhibited microtubule formation and induced expression of Bax, cleaved caspase-3, p53 and ROS, and inhibited Bcl-2 expression. DPMA also affected cyclinB1, cdc2 and p-cdc2 expression, inducing cell cycle arrest. DPMA also inhibited tube formation of VEGF-induced human umbilical vein endothelial cells. These studies demonstrate that DPMA inhibits p53/cdc2/Bax signaling, thereby inhibiting cell growth/angiogenesis and inducing apoptosis. PMID- 24231364 TI - Examining the utility of a bite-count-based measure of eating activity in free living human beings. AB - The obesity epidemic has triggered a need for novel methods for measuring eating activity in free-living settings. Here, we introduce a bite-count method that has the potential to be used in long-term investigations of eating activity. The purpose of our observational study was to describe the relationship between bite count and energy intake and determine whether there are sex and body mass index group differences in kilocalories per bite in free-living human beings. From October 2011 to February 2012, 77 participants used a wrist-worn device for 2 weeks to measure bite count during 2,975 eating activities. An automated self administered 24-hour recall was completed daily to provide kilocalorie estimates for each eating activity. Pearson's correlation indicated a moderate, positive correlation between bite count and kilocalories (r=0.44; P<0.001) across all 2,975 eating activities. The average per-individual correlation was 0.53. A 2 (sex)*3 (body mass index group: normal, overweight, obese) analysis of variance indicated that men consumed 6 kcal more per bite than women on average. However, there were no body mass index group differences in kilocalories per bite. This was the longest study of a body-worn sensor for monitoring eating activity of free-living human beings to date, which highlights the strong potential for this method to be used in future, long-term investigations. PMID- 24231365 TI - Getting a taste for food waste: a mixed methods ethnographic study into hospital food waste before patient consumption conducted at three New Zealand foodservice facilities. AB - Foodservice organizations, particularly those in hospitals, are large producers of food waste. To date, research on waste in hospitals has focused primarily on plate waste and the affect of food waste on patient nutrition outcomes. Less focus has been placed on waste generation at the kitchen end of the hospital food system. We used a novel approach to understand reasons for hospital food waste before consumption and offer recommendations on waste minimization within foodservices. A mixed methods ethnographic research approach was adopted. Three New Zealand hospital foodservices were selected as research sites, all of which were contracted to an external foodservice provider. Data collection techniques included document analyses, observations, focus groups with kitchen staff, and one-on-one interviews with managers. Thematic analysis was conducted to generate common themes. Most food waste occurred during service and as a result of overproduction. Attitudes and habits of foodservice personnel were considered influential factors of waste generation. Implications of food waste were perceived differently by different levels of staff. Whereas managers raised discussion from a financial perspective, kitchen staff drew upon social implications. Organizational plans, controls, and use of pre-prepared ingredients assisted in waste minimization. An array of factors influenced waste generation in hospital foodservices. Exploring attitudes and practices of foodservice personnel allowed an understanding of reasons behind hospital food waste and ways in which it could be minimized. This study provides a foundation for further research on sustainable behavior within the wider foodservice sector and dietetics practice. PMID- 24231366 TI - Validation of a food frequency questionnaire to assess macronutrient and micronutrient intake among Jordanians. AB - The aim of this study was to examine the validity and reliability of a food frequency questionnaire (FFQ) among a convenience sample of healthy adults in Jordan. A modified version of the questionnaire known as Diet History Questionnaire I, which measures dietary intakes over a 1-year period, was administrated to 101 apparently healthy men and women recruited from three large medical centers in Jordan. Fifty-five participants completed the modified FFQ and three 24-hour recalls. Participants (N=101) completed the FFQ two times separated by a 1-month period. Reliability of the FFQ was assessed using test-retest method. Mean age of participants was 33.4+/-18.5 years. Energy, carbohydrate, fiber, fat, saturated fat, calcium, and iron had deattenuated correlations of .732, .563, .544, .487, .484, .451, and .459, respectively. The FFQ and 24-hour recalls produced similar agreement percentages ranging between 25.5% and 43.6%. Mean energy-adjusted reliability coefficients ranged from .695 to .943. A Cronbach's alpha for the total FFQ items of .857 was found. The modified FFQ has reasonable relative validity and reliability for energy, carbohydrate, fiber, fat, saturated fat, calcium, and iron intakes in Jordanian adults over a 1-year period. However, its application may require additional modifications and validation efforts. Future research is warranted to further modify and test the FFQ in a larger and more diverse sample of Jordanians as well as to develop FFQ for the use among other age groups. PMID- 24231368 TI - Bisphenol A modulates the metabolic regulator oestrogen-related receptor-alpha in T-cells. AB - Bisphenol A (BPA) is a widely used plastics constituent that has been associated with endocrine, immune and metabolic effects. Evidence for how BPA exerts significant biological effects at chronic low levels of exposure has remained elusive. In adult men, exposure to BPA has been associated with higher expression of two nuclear receptors, oestrogen receptor-beta (ERbeta) and oestrogen-related receptor-alpha (ERRalpha), in peripheral white blood cells in vivo. In this study, we explore the expression of ESR2 (ERbeta) and ESRRA (ERRalpha) in human leukaemic T-cell lymphoblasts (Jurkat cells) exposed to BPA in vitro. We show that exposure to BPA led to enhanced expression of ESRRA within 6 h of exposure (mean+/-s.e.m.: 1.43+/-0.08-fold increase compared with the control, P<0.05). After 72 h, expression of ESRRA remained significantly enhanced at concentrations of BPA >=1 nM. Oxidative metabolism of BPA by rat liver S9 fractions yields the potent oestrogenic metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). Exposure of cells to 1-100 nM MBP increased the expression of both ESRRA (significantly induced, P<0.05, at 1, 10, 100 nM) and ESR2 (1.32+/-0.07-fold increase at 100 nM exposure, P<0.01). ERRalpha is a major control point for oxidative metabolism in many cell types, including T-cells. Following exposure to both BPA and MBP, we found that cells showed a decrease in cell proliferation rate. Taken together, these results confirm the bioactivity of BPA against putative T-cell targets in vitro at concentrations relevant to general human exposure. PMID- 24231369 TI - Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve. AB - The female germ line in mammals is subjected to massive cell death that eliminates 60-85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro apoptotic members of the BCL2 gene family. By contrast, the South American plains vizcacha, Lagostomus maximus, exhibits sustained expression of the anti-apoptotic BCL2 gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries of L. maximus from early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were <0.5% of the germ cell number, except at mid-gestation (3.62%). Mitotic proliferation, entrance into prophase I stage and primordial follicle formation occurred as overlapping processes from early pregnancy to birth. Germ cell number remained constant in early post-natal life, but a remnant population of non-follicular VASA- and PCNA-positive germ cells still persisted at post-natal day 60. L. maximus is the first mammal so far described in which female germ line develops in the absence of constitutive massive germ cell elimination. PMID- 24231371 TI - Ranking of the scientific production in Brazilian universities in the health science area - 1996 to 2011. PMID- 24231367 TI - Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography. AB - While islet transplantation is considered a useful therapeutic option for severe diabetes mellitus (DM), the outcome of this treatment remains unsatisfactory. This is largely due to the damage and loss of islets in the early transplant stage. Thus, it is important to monitor the condition of the transplanted islets, so that a treatment can be selected to rescue the islets from damage if needed. Recently, numerous trials have been performed to investigate the efficacy of different imaging modalities for visualizing transplanted islets. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities for this purpose. Some groups, including ours, have also tried to visualize transplanted islets by ultrasonography (US). In this review article, we discuss the recent progress in islet imaging. PMID- 24231372 TI - The antimicrobial effect of silicon nanowires decorated with silver and copper nanoparticles. AB - The paper reports on the preparation and antibacterial activity of silicon nanowire (SiNW) substrates coated with Ag or Cu nanoparticles (NPs) against Escherichia coli (E. coli) bacteria. The substrates are easily prepared using the metal-assisted chemical etching of crystalline silicon in hydrofluoric acid/silver nitrate (HF/AgNO3) aqueous solution. Decoration of the SiNWs with metal NPs is achieved by simple immersion in HF aqueous solutions containing silver or copper salts. The SiNWs coated with Ag NPs are biocompatible with human lung adenocarcinoma epithelial cell line A549 while possessing strong antibacterial properties to E. coli. In contrast, the SiNWs decorated with Cu NPs showed higher cytotoxicity and slightly lower antibacterial activity. Moreover, it was also observed that leakage of sugars and proteins from the cell wall of E. coli in interaction with SiNWs decorated with Ag NPs is higher compared to SiNWs modified with Cu NPs. PMID- 24231373 TI - Geographical distribution of the annual mean radon concentrations in primary schools of Southern Serbia - application of geostatistical methods. AB - Between 2008 and 2011 a survey of radon ((222)Rn) was performed in schools of several districts of Southern Serbia. Some results have been published previously (Zunic et al., 2010; Carpentieri et al., 2011; Zunic et al., 2013). This article concentrates on the geographical distribution of the measured Rn concentrations. Applying geostatistical methods we generate "school radon maps" of expected concentrations and of estimated probabilities that a concentration threshold is exceeded. The resulting maps show a clearly structured spatial pattern which appears related to the geological background. In particular in areas with vulcanite and granitoid rocks, elevated radon (Rn) concentrations can be expected. The "school radon map" can therefore be considered as proxy to a map of the geogenic radon potential, and allows identification of radon-prone areas, i.e. areas in which higher Rn radon concentrations can be expected for natural reasons. It must be stressed that the "radon hazard", or potential risk, estimated this way, has to be distinguished from the actual radon risk, which is a function of exposure. This in turn may require (depending on the target variable which is supposed to measure risk) considering demographic and sociological reality, i.e. population density, distribution of building styles and living habits. PMID- 24231374 TI - Cloning, expression of Aspergillus niger JL-15 endo-polygalacturonase A gene in Pichia pastoris and oligo-galacturonates production. AB - The endo-galacturonase A gene (pgaA) was cloned using the cDNAs synthesized from total RNA of Aspergillus niger JL-15 by reverse transcription as template. The open reading frame (ORF) of pgaA was 1113bp, encoding a peptide of 370 amino acids with the predicted molecular mass of 38.8kDa. The pgaA was successfully expressed in Pichia pastoris GS115 under the control of AOX1 promoter. After induction by methanol for 96h, the activity of the recombinant endo-galacturonase A (rePgaA) in culture supernatant was 2091.0U/mg. SDS-PAGE analysis showed that the molecular mass of rePgaA was about 40.0kDa. Enzymatic properties assays showed that the optimum temperature and pH for rePgaA were 50 degrees C and pH 5.0, respectively. The Michaelis-Menten constant (Km) and maximal velocity (Vmax) of rePgaA for citrus pectin were 3.20mgml(-1) and 40.97MUmolmin(-1)ml(-1), respectively. The rePgaA mediated a rapid decrease in viscosity of pectin solution with release of small amount of reducing sugar. High performance liquid chromatography (HPLC) analysis revealed that digalacturonate (G2) and trigalalcturonate (G3) were the main hydrolysis products released from pectin by rePgaA. The rePgaA showed very low activity on G2 and G3, which suggested it was a typical endo-acting enzyme. PMID- 24231375 TI - Microfluidic positioning of pollen grains in lab-on-a-chip for single cell analysis. AB - A lab-on-a-chip device with a knot shaped microfluidic network is presented to enable trapping of single pollen grains at the entrances of a series of microchannels. This set-up serves to create identical growth conditions for serially arranged tip growing plant cells such as pollen tubes. The design consists of an inlet to introduce the pollen suspension into the chip, three outlets to evacuate excess medium or cells, a distribution chamber to guide the pollen grains toward the growth microchannels and a serial arrangement of microchannels with different geometries connected to the distribution chamber. These microchannels are to harbor the individual pollen tubes. Two different criteria were established to assess the efficiency and optimize the device: trapping probability and uniformity of fluid flow conditions within the microchannels. The performance of different geometries of the microfluidic network was numerically analyzed and experimentally tested. PMID- 24231376 TI - Identification and characterization of UDP-glucose pyrophosphorylase in cyanobacteria Anabaena sp. PCC 7120. AB - Exopolysaccharides produced by photosynthetic cyanobacteria have received considerable attention in recent years for their potential applications in the production of renewable biofuels. Particularly, cyanobacterial cellulose is one of the most promising products because it is extracellularly secreted as a non crystalline form, which can be easily harvested from the media and converted into glucose units. In cyanobacteria, the production of UDP-glucose, the cellulose precursor, is a key step in the cellulose synthesis pathway. UDP-glucose is synthesized from UTP and glucose-1-phosphate (Glc-1P) by UDP-glucose pyrophosphorylase (UGPase), but this pathway in cyanobacteria has not been well characterized. Therefore, to elucidate the overall cellulose biosynthesis pathway in cyanobacteria, we studied the putative UGPase All3274 and seven other putative NDP-sugar pyrophosphorylases (NSPases), All4645, Alr2825, Alr4491, Alr0188, Alr3400, Alr2361, and Alr3921 of Anabaena sp. PCC 7120. Assays using the purified recombinant proteins revealed that All3274 exhibited UGPase activity, All4645, Alr2825, Alr4491, Alr0188, and Alr3921 exhibited pyrophosphorylase activities on ADP-glucose, CDP-glucose, dTDP-glucose, GDP-mannose, and UDP-N-acetylglucosamine, respectively. Further characterization of All3274 revealed that the kcat for UDP glucose formation was one or two orders lower than those of other known UGPases. The activity and dimerization tendency of All3274 increased at higher enzyme concentrations, implying catalytic activation by dimerization. However, most interestingly, All3274 dimerization was inhibited by UTP and Glc-1P, but not by UDP-glucose. This study presents the first in vitro characterization of a cyanobacterial UGPase, and provides insights into biotechnological attempts to utilize the photosynthetic production of cellulose from cyanobacteria. PMID- 24231377 TI - New fluorogenic dyes for analysis of cellular processes by flow cytometry and confocal microscopy. AB - Fluorescent microscopy and fluorescent imaging by flow cytometry are two of the fastest growing areas in the medical and biological research. Innovations in fluorescent chemistry and synthesis of new dye probes are closely related to the development of service equipment such as light sources, and detection techniques. Among compounds known as fluorescent labels, the cyanine-based dyes have become widely used since they have high excitation coefficients, narrow emission bands and high fluorescence upon binding to nucleic acids. The key methods for evaluation of apoptosis and cell cycle allow measuring DNA content by several flow cytometric techniques. We have synthesized new monomethine cyanine dyes and have characterized their applicability for staining of live and/or apoptotic cells. Imaging experiments by flow cytometry and confocal laser scanning microscopy (CLSM) have been also performed. Two of the dyes have shown high affinity binding to the nuclei at high dilutions, up to 10(-9)M. Flow cytometry and CLSM have confirmed that these dyes labeled selectively non-living, e.g. ethanol-fixed cells that makes them appropriate for estimations of cell viability and apoptosis. The novel structures proved to be appropriate also for analysis of the cell cycle. PMID- 24231378 TI - Evaluation of anti-nociceptive and anti-inflammatory activity of low-level laser therapy on temporomandibular joint inflammation in rodents. AB - The aim of this study was to investigate the analgesic and anti-inflammatory activity of low-level laser therapy (LLLT) on the nociceptive behavioral as well as histomorphological aspects induced by injection of formalin and carrageenan into the rat temporomandibular joint. The 2.5% formalin injection (FRG group) induced behavioral responses characterized by rubbing the orofacial region and flinching the head quickly, which were quantified for 45 min. The pretreatment with systemic administration of diclofenac sodium-DFN group (10 mg/kg i.p.) as well as the irradiation with LLLT infrared (LST group, 780 nm, 70 mW, 30 s, 2.1 J, 52.5 J/cm(2), GaAlAs) significantly reduced the formalin-induced nociceptive responses. The 1% carrageenan injection (CRG group) induced inflammatory responses over the time-course of the study (24 h, and 3 and 7 days) characterized by the presence of intense inflammatory infiltrate rich in neutrophils, scanty areas of liquefactive necrosis and intense interstitial edema, extensive hemorrhagic areas, and enlargement of the joint space on the region. The DFN and LST groups showed an intensity of inflammatory response that was significantly lower than in CRG group over the time-course of the study, especially in the LST group, which showed exuberant granulation tissue with intense vascularization, and deposition of newly formed collagen fibers (3 and 7 days). It was concluded that the LLLT presented an anti-nociceptive and anti inflammatory response on the inflammation induced in the temporomandibular joint of rodents. PMID- 24231379 TI - UVC inhibits collagen biosynthesis through up-regulation of NF-kappaB p65 signaling in cultured fibroblasts. AB - The effects of UVC on collagen biosynthesis, prolidase activity, expression of alpha2beta1 integrin, IGF-I receptor, FAK, MAP-kinases (ERK1 and ERK2) and the transcription factor NF-kappaB p65 were evaluated in human dermal fibroblasts. Confluent fibroblasts were treated with UVC light at a rates of 30 and 60 J/m(2). It was found that UVC-dependent decrease in collagen biosynthesis was not accompanied by parallel decrease in prolidase activity and expression. Since insulin-like growth factor receptor (IGF-IR) and alpha2beta1 integrin signaling are the most potent regulators of collagen biosynthesis, the effect of UVC on IGF IR and alpha2beta1 integrin receptor expressions were evaluated. It was found that the exposure of the cells to UVC contributed to decrease in alpha2beta1 integrin receptor and FAK expression and to an increase in IGF-IR and pERK1, pERK2 expressions. It was accompanied by an increase in the expression of NF kappaB p65, the known inhibitor of collagen gene expression. The data suggest that UVC-dependent decrease of collagen biosynthesis in cultured human skin fibroblasts results from decrease in alpha2beta1 integrin receptor signaling and activation of NF-kappaB p65, that is responsible for down-regulation of collagen gene expression. PMID- 24231380 TI - Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement. AB - Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used. PMID- 24231381 TI - Increased prevalence of aminoglycoside resistance in clinical isolates of Escherichia coli and Klebsiella spp. in Norway is associated with the acquisition of AAC(3)-II and AAC(6')-Ib. AB - In this study, we show that the increasing prevalence of aminoglycoside resistance observed in Norway among clinical Escherichia coli and Klebsiella spp. isolates is mainly due to the presence of the aminoglycoside-modifying enzymes AAC(3)-II and AAC(6')-Ib. A frequent co-association of aminoglycoside resistance with Cefotaximase-Munchen group 1 extended-spectrum beta-lactamases was also observed. PMID- 24231382 TI - PCR-restriction fragment length polymorphism analysis using groEL gene to differentiate pathogenic Vibrio species. AB - Important pathogenic Vibrio species were differentiated by PCR-restriction fragment length polymorphism analysis. A 1117-bp groEL gene product was amplified using universal primers and digested using the restriction enzymes NruI or XbaI, revealing unique digestion patterns for each of the 10 Vibrio species, of which 7 were pathogenic in humans, along with 2 other species pathogenic in fish. PMID- 24231383 TI - Development and validation of a multiplex PCR assay for identification of the epidemic ST-258/512 KPC-producing Klebsiella pneumoniae clone. AB - The Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-KP) sequence type (ST)-258/512 clone is the dominant clone by which KPC has disseminated worldwide. Standard typing methods are time-consuming and are therefore impractical for identification of this clone in the course of an outbreak. Through comparative genomic study, we have previously identified several presumably unique genes of this clone: 1) PILV-like protein (pilv-l), 2) transposase, IS66-family (is-66), and a 3) phage-related protein (prp). Our aims were to 1) test for the presence of these genes using a multiplex PCR in a large, multinational collection of KPC-KP isolates and to 2) validate this assay as a typing method for the identification of the ST-258/512 clone. KPC-KP isolates (n=160) that included both ST-258/512 (group A, n=114) and non-ST-258 (group B, n=46) strains were collected from the following countries: Greece, 20; Israel, 93; Italy, 19; USA, 25; and Colombia, 3. Group B included 30 different STs from various lineages. The pilv-l gene was present in 111/114 of ST-258 isolates, including all of the KPC-negative isolates resulting in a sensitivity of 97%. Using primers for a unique ST-258 pilv-l allele resulted in a specificity of 100%. The sensitivity values of is-66 and prp genes for detecting KPC-KP ST-258 were 83 and 89%, respectively, and the specificity values were 67 and 93%, respectively. PCR for the unique pilv-l ST-258 allele provides a reliable tool for rapid detection of the ST-258 clone. This method can be helpful both in the setting of an outbreak and in a large-scale survey of KPC-KP strains. PMID- 24231384 TI - Usefulness of a direct 16S rRNA gene PCR assay of percutaneous biopsies or aspirates for etiological diagnosis of vertebral osteomyelitis. AB - We performed a prospective study to evaluate the clinical usefulness of a direct 16S rRNA gene (16S rDNA) PCR assay of percutaneous biopsies or aspirates for the etiological diagnosis of vertebral osteomyelitis. During May 2009 to December 2010 and November 2011 to August 2012, consecutive patients with suspected vertebral osteomyelitis who underwent a percutaneous biopsy or aspiration were enrolled. Of 45 patients with vertebral osteomyelitis, 16S rDNA PCR was positive in 24 (53.3%), whereas culture was positive in 13 (28.9%) (P = 0.027). Three of PCR-positive cases (12.5%, 3/24) and 1 of culture-positive case (7.7%, 1/13) were considered to be false-positives. Of 16 patients without prior antimicrobial exposure, 75% of cases (12/16) were positive by either culture (7/16, 43.8%) or PCR (9/16, 56.3%). A 16S rDNA PCR assay with sequencing was more sensitive than routine culture for the etiological diagnosis of vertebral osteomyelitis. PMID- 24231386 TI - Grand total EEG as a predictive biomarker for cognitive impairment severity in cerebral infarcts of Chinese. AB - Cerebral infarct (CI) is a common disease of older adults, which increases the risk for cognitive impairment or dementia. CI-associated mild cognitive impairment is a potential prodromal stage of serious cognitive impairment. The grand total EEG (GTE) score is a rating scale for clinical electroencephalography (EEG) analyses, which is useful in the evaluation of different types of cognitive impairment. Sixty-five patients with CI underwent neuropsychological testing and resting state EEG. Spearman rank correlation analysis was used to investigate the relationship between a short version of the GTE score and severity of cognitive impairment in CI. Significant correlations with deteriorating cognition (combined Montreal Cognitive Assessment/clock drawing test) were found for the overall short GTE score (Spearman rank correlation, p = -0.61, r = -0.88491, P = 0.009) and for the subscore "Frequency of Rhythmic Background Activity" (p = -0.63, r = 0.92559, P = 0.007). In conclusion, the GTE short score and Frequency of Rhythmic Background Activity were increased with the deteriorating cognitive impairment in patients with CI. PMID- 24231385 TI - Surface modification of graphene nanopores for protein translocation. AB - Studies of DNA translocation through graphene nanopores have revealed their potential for DNA sequencing. Here we report a study of protein translocation through chemically modified graphene nanopores. A transmission electron microscope (TEM) was used to cut nanopores with diameters between 5 and 20 nm in multilayer graphene prepared by chemical vapor deposition (CVD). After oxygen plasma treatment, the dependence of the measured ionic current on salt concentration and pH was consistent with a small surface charge induced by the formation of carboxyl groups. While translocation of gold nanoparticles (10 nm) was readily detected through such treated pores of a larger diameter, translocation of the protein ferritin was not observed either for oxygen plasma treated pores, or for pores modified with mercaptohexadecanoic acid. Ferritin translocation events were reliably observed after the pores were modified with the phospholipid-PEG (DPPE-PEG750) amphiphile. The ion current signature of translocation events was complex, suggesting that a series of interactions between the protein and pores occurs during the process. PMID- 24231387 TI - The AGE-RAGE pathway and its relation to cardiovascular disease in patients with chronic kidney disease. AB - Chronic kidney disease (CKD) carries an unequivocal high risk for cardiovascular disease (CVD) contributing to high morbimortality; however, the underlying reasons are not fully known. Among mechanisms involved in the pathophysiology of CVD, chronic overstimulation of the advanced glycation end-products (AGE) receptor for AGE (RAGE) pathway is likely a major contributor in patients with CKD. This review describes briefly some of the components of this pathway, highlighting especially differences between circulating AGE and tissue AGE and how activation of the AGE-RAGE pathway may promote CVD in CKD. PMID- 24231388 TI - Scaling up of family planning in low-income countries: lessons from Ethiopia. PMID- 24231390 TI - Genotypic diversity in Babesia bovis field isolates and vaccine strains from South Africa. AB - Genotypic diversity in Babesia bovis (cause of Asiatic redwater in cattle) vaccine strains and field isolates from South Africa were investigated using the Bv80 gene as well as microsatellites. The S11 vaccine strain possessed both A and B alleles of the Bv80 gene, as well as genotypic diversity within each allele type as defined by repeat variation resulting in different amplicon sizes. Rapid serial passage of vaccine strain from passage S10 to S24 resulted in loss of genotypic diversity that yielded a single allele A genotype with an amplicon size of 558 bp. This suggested that clonal selection occurred during rapid passaging. Extensive genotypic diversity exists in 44 field isolates characterized with both Bv80 A and B alleles, but can be readily distinguished from the S24 vaccine strain using either the Bv80 allele specific PCR assays or using multi-locus micro-satellite typing. This indicated that no recent documented clinical cases of Asiatic redwater were caused by the reversion to virulence of the current vaccine strain. PMID- 24231389 TI - Inhibition of homologous recombination with vorinostat synergistically enhances ganciclovir cytotoxicity. AB - The nucleoside analog ganciclovir (GCV) elicits cytotoxicity in tumor cells via a novel mechanism in which drug incorporation into DNA produces minimal disruption of replication, but numerous DNA double strand breaks occur during the second S phase after drug exposure. We propose that homologous recombination (HR), a major repair pathway for DNA double strand breaks, can prevent GCV-induced DNA damage, and that inhibition of HR will enhance cytotoxicity with GCV. Survival after GCV treatment in cells expressing a herpes simplex virus thymidine kinase was strongly dependent on HR (>14-fold decrease in IC50 in HR-deficient vs. HR proficient CHO cells). In a homologous recombination reporter assay, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA; vorinostat), decreased HR repair events up to 85%. SAHA plus GCV produced synergistic cytotoxicity in U251tk human glioblastoma cells. Elucidation of the synergistic mechanism demonstrated that SAHA produced a concentration-dependent decrease in the HR proteins Rad51 and CtIP. GCV alone produced numerous Rad51 foci, demonstrating activation of HR. However, the addition of SAHA blocked GCV-induced Rad51 foci formation completely and increased gammaH2AX, a marker of DNA double strand breaks. SAHA plus GCV also produced synergistic cytotoxicity in HR proficient CHO cells, but the combination was antagonistic or additive in HR deficient CHO cells. Collectively, these data demonstrate that HR promotes survival with GCV and compromise of HR by SAHA results in synergistic cytotoxicity, revealing a new mechanism for enhancing anticancer activity with GCV. PMID- 24231391 TI - Silicified structures affect leaf optical properties in grasses and sedge. AB - Silicon (Si) is an important structural element that can accumulate at high concentrations in grasses and sedges, and therefore Si structures might affect the optical properties of the leaves. To better understand the role of Si in light/leaf interactions in species rich in Si, we examined the total Si and silica phytoliths, the biochemical and morphological leaf properties, and the reflectance and transmittance spectra in grasses (Phragmites australis, Phalaris arundinacea, Molinia caerulea, Deschampsia cespitosa) and sedge (Carex elata). We show that these grasses contain >1% phytoliths per dry mass, while the sedge contains only 0.4%. The data reveal the variable leaf structures of these species and significant differences in the amount of Si and phytoliths between developing and mature leaves within each species and between grasses and sedge, with little difference seen among the grass species. Redundancy analysis shows the significant roles of the different near-surface silicified leaf structures (e.g., prickle hairs, cuticle, epidermis), phytoliths and Si contents, which explain the majority of the reflectance and transmittance spectra variability. The amount of explained variance differs between mature and developing leaves. The transmittance spectra are also significantly affected by chlorophyll a content and calcium levels in the leaf tissue. PMID- 24231392 TI - Highly active lanthanum doped ZnO nanorods for photodegradation of metasystox. AB - La-doped ZnO nanorods with different La contents were synthesized by microwave assisted method and characterized by various sophisticated techniques such as XRD, UV-Vis., EDS, XPS, SEM and TEM. The XRD patterns of the La-doped ZnO indicate hexagonal crystal structure with an average crystallite size of 30nm. It was found that the crystallite size of La-doped ZnO is much smaller as compared to pure ZnO and decreases with increasing La content. The photocatalytic activity of 0.5mol% La-doped ZnO in the degradation of metasystox was studied. It was observed that degradation efficiency of metasystox over La-doped ZnO increases up to 0.5mol% doping then decreases for higher doping levels. Among the catalyst studied, the 0.5mol% La-doped ZnO was the most active, showing high photocatalytic activity for the degradation of metasystox. The maximum reduction of concentration of metasystox was observed under static condition at pH 8. Reduction in the Chemical Oxygen Demand (COD) of metasystox was observed after 150min. The cytotoxicological studies of meristematic root tip cells of Allium cepa were studied. The results obtained indicate that photocatalytically degraded products of metasystox were less toxic as compared to metasystox. PMID- 24231393 TI - Phytochemical and pharmacological profile of Ipomoea aquatica. AB - Ipomoea aquatica (I. aquatica) (Convolvulaceae) is commonly grown green leafy vegetable found throughout India, Ceylon, Tropical Asia, Africa, and Australia. Traditionally, I. aquatica used as carminative agent and lessens inflammation, and is useful in fever, jaundice, biliousness, bronchitis, liver complaints, etc., I. aquatica is a rich source of vitamins, minerals, proteins, fibers, carotenes, and flavanoids with many health benefits. The objective of this review is to highlight the pharmacognostical, phytochemical, and pharmacological information of this plant. PMID- 24231394 TI - Responses to glycemic control therapy according to age, gender, level of adiposity, and duration of diabetes in type 2 diabetic patients. AB - CONTEXT: It is established that glycemic control measures involving diet and oral medication reduces glycated hemoglobin concentration (HbA1c) in type 2 diabetic patients. AIMS: To determine whether glycemic levels after diabetic treatment is affected by age, gender, obesity, and diabetic duration in type 2 diabetic patients. SETTINGS AND DESIGN: A total of 52 type 2 diabetic patients participated in a 12-week diabetic management therapy involving oral medication (metformin) and lifestyle intervention (diet). MATERIALS AND METHODS: We compared the glycated hemoglobin reduction after treatment between the elderly and non elderly; males and females; obese and non-obese; and newly diagnosed and long standing diabetics. RESULTS: After the diabetic treatment, participants' mean HbA1c level indicated a reduction of 1.1 +/- 1.31%, weight loss of 2.46 +/- 1.79 kg, and BMI reduction of 0.94 +/- 0.69 kg/m 2 . A total of 23 (44.2%) patients had an acceptable HbA1c level of <6.5%. Significantly greater HbA1c reduction was observed in non-elderly, non-overweight/obese, and newly diagnosed diabetic patients compared to the elderly, overweight/obese, and long-standing diabetic patients respectively (P < 0.05 or P < 0.01). HbA1c reduction did not indicate sex differences. CONCLUSION: The present findings suggest lower responses to glycemic control therapy in elderly, overweight/obese, and long-standing diabetic patients when compared to the non-elderly, non-overweight/obese, and newly diagnosed diabetic patients. It is recommended that treatment criteria for type 2 diabetes should account for the age, level of adiposity, and diabetic duration of the patient in order to make optimal therapeutic decisions for the treatment of diabetes mellitus in adults. PMID- 24231395 TI - The effect of a healthy lifestyle program on the elderly's health in Arak. AB - BACKGROUND: Increasing life-expectancy and decreasing birth rate have led to an increase in the elderly population worldwide so that the aging population is considered one of the biggest public health concerns in the present century which demands more attention to this vulnerable group. Therefore, the present study was done to determine the effect of a healthy lifestyle program on elderly's health in Arak. MATERIALS AND METHODS: This quasi-experimental intervention study was carried out on 60 elderly citizens of Arak. The participants attended four instructional classes on nutrition, exercise, sleep hygiene, life skills, and personal hygiene over one month and they were followed for three months after the intervention. Data were collected through standard quality of life questionnaire (SF-36) and Katz standard ADLs in the elderly questionnaire before and three months after the completion of the study. RESULTS: The average age of the participants was 67.61 +/- 5.02 years. In terms of gender, the majority of the participants (60%) were male. In terms of quality of life before the instructional intervention, 13.3% of the participants were in low level, 30% in average level, 41.7% in good level, and 15% in the high level of quality of life. However, after the intervention, the majority of the participants were in good (38.3%) and high (45%) levels of quality of life which showed significant differences before and after the instructional intervention (P < 0.001). Moreover, there was a significant difference between Katz ADLs in the elderly before and after the intervention (P < 0.001). CONCLUSION: The comparison between the quality of life and ADLs in the elderly before and after the intervention showed that continuing instruction for the elderly based on a regular healthy lifestyle program is effective and holding different instructional classes for this population, that is often ignored, seems necessary. The findings of this study can help design proper instructional guidelines on healthy lifestyle in the elderly. PMID- 24231396 TI - Effect of inhaled fluticasone and salmeterol on tracheal responsiveness and lung inflammation: influence of administration time and allergen-free period. AB - BACKGROUND: The effect of inhaled fluticasone propionate (FP) and salmeterol (SM) on tracheal responsiveness (TR) to methacholine and lung pathology of sensitized guinea pig was examined. MATERIALS AND METHODS: Six groups of guinea pigs (n = 7) were sensitized to ovalbumin (OA). Three groups were subjected to inhaled FP and SM, one group during (A), one group after sensitization (for 18 days, B) and other group during sensitization but with 18-days delay before measurements (C). Other three groups were treated with placebo. RESULTS: The TR to methacholine and tracheal muscle contractility were significantly higher than those of control group (P < 0.001 for all cases). The lungs of placebo groups showed variable pathological changes (nonsignificant to P < 0.001) compared to control group. TR, intra-alveolar and interabronchoal hemorrhagie (P < 0.001 in only group A) in treated groups with FP and SM were significantly decreased compared to placebo groups. The improvement in all variables in treatment groups A and C were more pronounced than group B. CONCLUSION: These results showed a protective effect of FP and SM on tracheal responsiveness and lung pathology during sensitization which was more effective than after sensitization. PMID- 24231397 TI - Qualitative research: a brief description. AB - Qualitative research refers to, a range of methodological approaches which aim to generate an in-depth and interpreted understanding of the social world, by learning about people's social and material circumstances, their experiences, perspectives, and histories. Requires researchers to become intensely involved, often remaining in field for lengthy periods of time. The greatest value of qualitative research is its ability to address questions of relevance to public health knowledge and practice which are difficult to answer satisfactorily using quantitative methods. PMID- 24231399 TI - Self-regulation of the anterior insula: Reinforcement learning using real-time fMRI neurofeedback. AB - The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants was shown 'control' feedback from another brain area. Pre- and post training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF. In contrast to the controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and SCR to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI/control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed that the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate. PMID- 24231398 TI - Guest list or black list: heritable small RNAs as immunogenic memories. AB - Small RNA-mediated gene silencing plays a pivotal role in genome immunity by recognizing and eliminating viruses and transposons that may otherwise colonize the genome. However, individual genomic parasites are highly diverse and employ multiple immune-evasion techniques, making this silencing challenging. Here I review a new theory proposing that the integrity of the germline is maintained by transgenerationally transmitted RNA 'memories' that record ancestral gene expression patterns and delineate 'self' from 'foreign' sequences. To maintain such recollection, two tactics are employed in parallel: 'black listing' of invading nucleic acids and 'guest listing' of endogenous genes. Studies in several organisms have shown that this memorization is used by the next generation of small RNAs to act as 'inherited vaccines' that attack invading elements or as 'inherited licenses' that permit the transcription of autogenous sequences. PMID- 24231400 TI - Impact of physical exercise on reaction time in patients with Parkinson's disease data from the Berlin BIG Study. AB - OBJECTIVE: To determine whether physical activity may affect cognitive performance in patients with Parkinson's disease by measuring reaction times in patients participating in the Berlin BIG study. DESIGN: Randomized controlled trial, rater-blinded. SETTING: Ambulatory care. PARTICIPANTS: Patients with mild to moderate Parkinson's disease (N=60) were randomly allocated to 3 treatment arms. Outcome was measured at the termination of training and at follow-up 16 weeks after baseline in 58 patients (completers). INTERVENTIONS: Patients received 16 hours of individual Lee Silverman Voice Treatment-BIG training (BIG; duration of treatment, 4wk), 16 hours of group training with Nordic Walking (WALK; duration of treatment, 8wk), or nonsupervised domestic exercise (HOME; duration of instruction, 1hr). MAIN OUTCOME MEASURES: Cued reaction time (cRT) and noncued reaction time (nRT). RESULTS: Differences between treatment groups in improvement in reaction times from baseline to intermediate and baseline to follow-up assessments were observed for cRT but not for nRT. Pairwise t test comparisons revealed differences in change in cRT at both measurements between BIG and HOME groups (intermediate: -52ms; 95% confidence interval [CI], -84/-20; P=.002; follow-up: 55ms; CI, -105/-6; P=.030) and between WALK and HOME groups (intermediate: -61ms; CI, -120/-2; P=.042; follow-up: -78ms; CI, -136/-20; P=.010). There was no difference between BIG and WALK groups (intermediate: 9ms; CI, -49/67; P=.742; follow-up: 23ms; CI, -27/72; P=.361). CONCLUSION: Supervised physical exercise with Lee Silverman Voice Treatment-BIG or Nordic Walking is associated with improvement in cognitive aspects of movement preparation. PMID- 24231401 TI - Retrieval practice improves memory in survivors of severe traumatic brain injury. AB - OBJECTIVE: To investigate whether retrieval practice (RP) improves delayed recall after short and long delays in survivors of severe traumatic brain injury (TBI) relative to massed restudy (MR) and spaced restudy (SR). DESIGN: 3(learning condition: MR, SR, RP)*2(delayed recall: 30min, 1wk) within-subject experiment. SETTING: Nonprofit medical rehabilitation research center. PARTICIPANTS: Memory impaired (<5th percentile) survivors of severe TBI (N=10). INTERVENTION: During RP, patients are quizzed on to-be-learned information shortly after it is presented, such that patients practice retrieval. MR consists of repeated restudy (ie, cramming). SR consists of restudy trials separated in time (ie, distributed learning). MAIN OUTCOME MEASURES: Forty-eight verbal paired associates (VPAs) were equally divided across 3 learning conditions (16 per condition). Delayed recall for one half of the VPAs was assessed after 30 minutes (8 per condition) and for the other half after 1 week (8 per condition). RESULTS: There was a large effect of learning condition after the short delay (P<.001, eta(2)=.72), with much better recall of VPAs studied through RP (46.3%) relative to MR (12.5%) and SR (15.0%). This large effect of learning condition remained after the long delay (P=.001, eta(2)=.56), as patients recalled 11.3% of the VPAs studied through RP, but nothing through MR (0.0%) and only 1.3% through SR. That is, RP was essentially the only learning condition to result in successful recall after 1 week, with most patients recalling at least 1 VPA. CONCLUSIONS: The robust effect of RP among TBI survivors with severe memory impairment engenders confidence that this strategy would work outside the laboratory to improve memory in real-life settings. Future randomized controlled trials of RP training are needed. PMID- 24231403 TI - Assessing arsenic intake from groundwater and rice by residents in Prey Veng province, Cambodia. AB - We investigated total daily intake of As by residents in Prey Veng province in the Mekong River basin of Cambodia. Groundwater (n = 11), rice (n = 11) and fingernail (n = 23) samples were randomly collected from the households and analyzed for total As by inductively coupled plasma mass spectrometry. Calculation indicated that daily dose of inorganic As was greater than the lower limits on the benchmark dose for a 0.5% increased incidence of lung cancer (BMDL0.5 equals to 3.0 MUg d(-1) kg(-1)body wt.). Moreover, positive correlation between As in fingernail and daily dose of As from groundwater and rice and total daily dose of As were found. These results suggest that the Prey Veng residents are exposed to As in groundwater. As in rice is an additional source which is attributable to high As accumulation in human bodies in the Mekong River basin of Cambodia. PMID- 24231402 TI - Relation of stride activity and participation in mobility-based life habits among children with cerebral palsy. AB - OBJECTIVE: To examine the relation between walking performance and participation in mobility-related habits of daily life in children with cerebral palsy (CP). To date, walking outcomes in CP have been capacity-based (what a child does in structured setting). Physical activity performance (what a child really does in daily life) has been documented to affect the relation of capacity-based gross motor measures and participation. DESIGN: Cross-sectional prospective cohort study. SETTING: Regional pediatric specialty care centers. PARTICIPANTS: A cohort of ambulatory children with CP (N=128; age, 2 to 9y; 41% girls; 49% having hemiplegia) participated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking performance was quantified from a 5-day sample of accelerometry data. Stride activity was summarized through the outcomes of the average number of total strides per day (independent of intensity) and the average number of total strides per day at >30 strides/min (marker of intensity). Mobility-based participation was assessed by using the Assessment of Life Habits for Children questionnaire categories of personal care, housing, mobility, and recreation. Regression models were developed controlling for sex, age, cognition, communication, pain, and body composition. RESULTS: The average number of total strides per day was positively associated with the personal care, housing, mobility, and recreation Assessment of Life Habits for Children questionnaire categories (beta=.34-.41, P<.001). The average number of total strides per day at >30 strides/min was associated with all categories (beta=.54-.60, P<.001). CONCLUSIONS: Accelerometry-based walking activity performance is significantly associated with levels of participation in mobility-based life habits for ambulatory children with CP. Evaluation of other factors and the direction of the relation within the International Classification of Functioning, Disability and Health is warranted to inform rehabilitation strategies. PMID- 24231404 TI - A dangerous Cushing response in a child: neurogenic heart damage. AB - Cushing response, which acts to preserve cerebral blood flow by inducing arterial hypertension, could induce neurogenic heart damage through hyperactivation of autonomic nervous system. Most of clinical reports describe neurogenic heart damage as a self-limiting condition clinically characterized by electrocardiographic abnormalities in the setting of an acute neurologic insult. Here we describe a case of life-threatening cardiac dysfunction immediately after a massive intracerebral hemorrhage in a healthy 7-year-old child. The low probability of ischemic heart disease, the poor increase of cardiac necrosis markers, the localization of regional wall motion abnormalities that are not typical for coronary artery disease, and reversibility after brain surgical decompression are consistent all with neurogenic heart damage. Acute decrease of brain oxygen delivery caused by cardiac dysfunction worsens secondary brain injury in the setting of an acute neurologic insult. Thus, Cushing response, which is a physiological mechanism of cerebral protection, could become a double edged sword when massive sympathetic activation makes the myocardium stunned. PMID- 24231405 TI - Evaluation of drug delivery to intact and porated skin by coherent Raman scattering and fluorescence microscopies. AB - Stimulated Raman scattering microscopy was used to assess the permeation of topically applied drugs and formulation excipients into porcine skin. This chemically selective technique generates high-resolution 3D images, from which semi-quantitative information may be elucidated. Ibuprofen, applied as a close-to saturated solution in propylene glycol, was directly observed to crystallise in/on the skin, as the co-solvent permeated more rapidly, resulting in precipitation of the drug. Coherent Raman scattering microscopy is also an excellent tool, in conjunction with more conventional confocal fluorescence microscopy, with which to image micro/nanoparticle-based formulations. Specifically, the uptake of particles into thermal ablation transport pathways in the skin has been examined. PMID- 24231406 TI - The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan. AB - The use of liposomal delivery systems for the treatment of cancer has been extensively researched because of their passive targeting to the vasculature of solid tumors. While their potential to provide prolonged retention and high drug encapsulation is desirable for anticancer agents, a mechanistic understanding is required to optimize and design liposomal drug delivery systems capable of controllable release tailored to tumor type and patient. Topotecan (TPT) is a topoisomerase I inhibitor that undergoes reversible, pH-sensitive ring-opening hydrolysis. TPT may benefit from liposomal formulation using active loading strategies to generate low intravesicular pH to prolong drug retention and increase drug encapsulation. This paper develops a mathematical model to describe TPT's permeability as a function of pH by accounting for the drug's ionization state, membrane binding, and ring-opening interconversion kinetics. Studies were conducted to determine the acid dissociation constant of TPT's phenolic -OH and interconversion kinetics between TPT's lactone and carboxylate forms. Using the constants determined from these studies and release studies conducted at varying pH, permeability coefficients and membrane binding constants for each species of TPT were determined. Based on this model, three permeable species were observed. Interestingly, the two most permeable species were zwitterionic forms of TPT, and the permeability of the lactone zwitterion was comparable to that of the neutral form of another camptothecin analogue. Furthermore, release was affected by based catalyzed interconversion kinetics between TPT's lactone and carboxylate forms. At neutral pH, release was rate-limited by formation of the TPT lactone from the ring-opened carboxylate form. Based on these findings, the developed model describing liposomal release of TPT may be used in the future to evaluate and optimize loading and subsequent release of liposomal TPT formulations utilizing active loading strategies. PMID- 24231408 TI - Reliability and stability of performances in 400-m swimming and 1500-m running. AB - PURPOSE: To assess the reliability and stability of 400-m swimming and 1500-m running competitions to establish the number of samples needed to obtain a stable pacing profile. Coaches, athletes, and researchers can use these methods to ensure that sufficient data are collected before training and race strategies are constructed or research conclusions are drawn. METHOD: Lap times were collected from 5 world and European championship finals between 2005 and 2011, resulting in the capture of data from 40 swimmers and 55 runners. A cumulative mean for each lap was calculated, starting with the most recent data, and the number of races needed for this to stabilize to within 1% was reported. Typical error for each lap was calculated for athletes who had competed in more than 1 final. RESULTS: International swimmers demonstrated more reproducible performances than runners in 3 of the 4 laps of the race (P < .01). Variance in runners' lap times significantly decreased by 1.7-2.7% after lap 1, whereas variance in swimmers' lap times tended to increase by 0.1-0.5% after lap 1. To establish a stable profile, at least ten 400-m swimmers and forty-four 1500-m runners must be included. CONCLUSIONS: A stable race profile was observed from the analysis of 5 events for 1500-m running and 3 events for 400-m swimming. Researchers and athletes can be more certain about the pacing information collected from 400-m swimming than 1500-m running races, as the swimming data are less variable, despite both events being of similar duration. PMID- 24231407 TI - A novel cationic niosome formulation for gene delivery to the retina. AB - Niosomes represent a recent promising approach for gene delivery purposes. We elaborated on a novel niosome formulation based on the 2,3 di(tetradecyloxy)propan-1-amine cationic lipid, combined with squalene and polysorbate 80 to evaluate the transfection efficiency in rat retinas. Niosomes prepared by the solvent emulsification-evaporation technique were mixed with the pCMSEGFP plasmid to form lipoplexes which were characterized in terms of morphology, size, surface charge, and DNA condensation, protection and release. In vitro studies were conducted to evaluate transfection efficiency, viability and internalization mechanism in HEK-293 and ARPE-19 cells. The efficacy of the most promising formulation was evaluated in rat eyes by monitoring the expression of the EGFP after intravitreal and subretinal injections. Lipoplexes at 15/1 ratio were 200nm in size, 25mV in zeta potential and exhibited spherical morphology. At this ratio, niosomes condensed and protected the DNA from enzymatic digestion. Lipoplexes successfully transfected HEK-293 and specially ARPE-19 cells, without affecting the viability. Whereas lipoplexes entered mainly retinal cells by clathrin-mediated endocytosis, HEK-293 cells showed a higher caveolae-dependent entry. After ocular administration, the expression of EGFP was detected in different cells of the retina depending on the administration route. This novel niosome formulation represents a promising approach to deliver genetic material into the retina to treat inherited retinal diseases. PMID- 24231409 TI - Mycobacterium genavense specific mesenteritic syndrome in HIV-infected patients: a new entity of retractile mesenteritis? AB - Abdominal mesenteritis is a rare and poorly understood gastroenterological disease. Here, we report on two identical cases of Mycobacterium genavense associated retractile mesenteritis in HIV-positive patients. A literature search retrieved only few small retrospective studies, which characterize the clinical course of this seldom infection. We propose a pathogen-specific syndrome of retractile mesenteritis in HIV-positive patients linked to Mycobacterium genavense infection on the basis of our clinical observation and literature meta analysis with duodenal wall thickening, central mesenterial mass and vascular complications. PMID- 24231410 TI - Vesicular gold assemblies based on host-guest inclusion and its controllable release of doxorubicin. AB - We have developed a kind of gold nanoparticle (AuNP) in which polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) are attached on the surface of a gold nanocrystal through the host-guest inclusion between adamantane groups (ADA) and beta-cyclodextrin (beta-CD). The resulting AuNPs become amphiphilic in water above body temperature and self-assemble into vesicles. It is found that these vesicles can load doxorubicin (Dox) effectively. With a decrease in temperature, the PNIPAM shifted from hydrophobic to hydrophilic, causing Au vesicles to disassemble into stable small AuNPs, triggering the release of Dox. These hybrid vesicles, combining polymer functionality with the intriguing properties of AuNPs, can first release free Dox and AuNP/Dox at a site of a tumor through the application of either simple ice packs or deeply penetrating cryoprobes, then the AuNP/Dox can be taken in by tumor cells and destroy them like miniature munitions. Furthermore, these vesicles showed other therapeutic possibilities due to the presence of gold. We believe that the development of such multi-functional vesicles will provide new and therapeutically useful means for medical applications. PMID- 24231412 TI - The new European Society of Cardiology e-learning platform. PMID- 24231411 TI - Impact of personally measured pollutants on cardiac function. AB - Epidemiological studies have shown associations between ambient air pollution and changes in heart rate variability (HRV). However, studies using personal air pollution measurements, especially with exposure averages <24h, are still rare. Between February and March 2008 HRV data as well as personal exposure to particulate matter <2.5MUm (PM2.5), and particle number concentrations (PNC) were collected in five volunteers for up to 8.3h on a 5min resolution. Information about the participant's whereabouts was also collected. Mixed models were used to analyze concurrent and up to 30min delayed effects of air pollutants as well as being in traffic on 5min-averages of heart rate (HR), high and low frequency power (HF and LF), standard deviation of all normal-to-normal intervals (SDNN), and the root mean square of successive interval differences (RMSSD). Results are presented as %-change from the mean per increase in interquartile range of air pollutant. In total, 474 5-min segments were available for analysis. We observed concurrent and delayed reductions in SDNN of about 0.8-1.0% in association with a 5.4MUg/m(3) increase in PM2.5. However, being in traffic by car led to an increase of about 20% 10-14min and 15-19min later. An increase in PM2.5 or PNC was associated with lagged decreases for RMSSD and HF. We detected concurrent reductions in RMSSD (-17.6% [95%-confidence interval: 29.1; -4.3]) when being in traffic by bike/foot. Being in traffic by car was associated with an immediate reduction in LF while more delayed increases in LF were observed when being in traffic by bike/foot. Air pollution and traffic effects on HR were less consistent. These rapid changes in HRV within 30min might be mediated by the autonomic nervous system in response to direct reflexes from receptors in the lungs. PMID- 24231413 TI - Medial maxillectomy in recalcitrant sinusitis: when, why and how? AB - PURPOSE OF REVIEW: We reviewed all journal articles relevant to endoscopic medial maxillectomy in patients with recalcitrant chronic maxillary sinusitis in order to present all indications, the underlying pathophysiology and the developed surgical techniques. RECENT FINDINGS: Despite the high success rate of middle meatal antrostomy, cases with persistent maxillary sinus disease exist and often need a more extended endoscopic procedure for the better control of the disease. Such surgical option uses gravity for better sinus drainage and offers better saline irrigation, local application of medications and follow-up inspection. An endoscopic medial maxillectomy and its modified forms offer a wider surgical field and access to all 'difficult' areas of the maxillary sinus. SUMMARY: Patients with previous limited endoscopic sinus surgery or extended open surgery, cystic fibrosis, extensive mucoceles, allergic fungal sinusitis, odontogenic infections, foreign bodies and so on may suffer from recurrent disease requiring an endoscopic medial maxillectomy. Depending on the disease, various modifications of the procedure can be performed preserving the anterior buttress, nasolacrimal duct and inferior turbinate if possible. PMID- 24231414 TI - Suppression of colorectal cancer subcutaneous xenograft and experimental lung metastasis using nanoparticle-mediated drug delivery to tumor neovasculature. AB - Antiangiogenic therapy is a validated approach for colorectal cancer (CRC) treatment. However, diverse adverse effects inevitably appear due to the off target effect of the approved antiangiogenic inhibitors on the physiological functions and homeostasis. This study was to investigate a new tumor vessel targeting nanoparticulate drug delivery system, F56 peptide conjugated nanoparticles loading vincristine (F56-VCR-NP), for the effective treatment of CRC subcutaneous xenograft and experimental lung metastasis model. The controlled release behavior and in vivo pharmacokinetic profile of F56-VCR-NP were characterized. The tumor vessel targeting and antiangiogenic activity of F56-VCR NP was evaluated in human umbilical vein endothelial cells (HUVEC, a classical cell model mimicking tumor vascular EC), subcutaneous human HCT-15 xenograft in immunodeficient nude mice, and experimental CT-26 lung metastasis model in immunocompetent mice. The therapeutic efficacy (animal survival and toxicity) was further investigated in the model of CT-26 lung metastasis in mice. F56-VCR-NP could achieve 30-day controlled drug release in PBS (pH 7.4) and exhibited favorable long-circulating feature in vivo. F56-VCR-NP could accurately target the CRC neovasculature and elicit nanoparticle internalization in the tumor vascular EC, where the antiangiogenic VCR-induced dramatic EC apoptosis and necrosis of CRC tissue. F56-VCR-NP significantly prolonged the mouse survival with no obvious toxicity (weight loss and anepithymia) in the CT-26 lung metastasis mice model, and this pronounced antitumor effect was closely related with the decreased microvessel density in the metastases. The present nanoparticle-based targeted antiangiogenic therapy may provide a new promising approach for the therapy of CRC and lung metastasis, which deserves further translational research. PMID- 24231415 TI - The correlation between serum leptin and blood pressure after exposure to noise at work. AB - Several epidemiologic studies have reported that exposure to noise is associated with cardiovascular disease. The increased body weight is often associated with metabolic as well as increased blood pressure. The aim of this study is to investigate the correlation between the elevation of blood pressure and serum leptin hormones due to the effects of noise in the work place. A total of 80 volunteer males where included in this study with an age range between of 20 and 45 years, they were divided in two groups equally, the 1 st group were exposed to noise in the workplace while the 2 nd group were not. The individual noise exposure was determined by using a sound level meter. The range of noise was 80 100 dBA. Body Mass Index was also taken for each individual by a standard measure, blood pressure was measured by OMRON sphygmomanometer and serum leptin was measured through venous blood sample analysis enzyme linked immunosorbent assay. Spearman rank order correlation was used to examine the correlations between Blood pressure value (Systolic, Diastolic) and Leptin. All the relationships between parameters showed a positive correlation. Systolic and diastolic blood pressure values had a significant correlation to leptin hormone level in comparison to the control. There was a significant relation between leptin and blood pressure. leptin effects on the sympathetic nervous system may provide a partial explanation. Therefore, Leptin might have diverse cardiovascular actions. PMID- 24231416 TI - Evaluation of the effects of exposure to organic solvents and hazardous noise among US Air Force Reserve personnel. AB - Hearing loss affects many workers including those in the military and may be caused by noise, medications, and chemicals. Exposures to some chemicals may lead to an increase in the incidence of hearing loss when combined with hazardous noise. This retrospective study evaluated the risk for hearing loss among Air Force Reserve personnel exposed to occupational noise with and without exposures to toluene, styrene, xylene, benzene, and JP-8 (jet fuel). Risk factors associated with hearing loss were determined using logistic and linear regression. Stratified analysis was used to evaluate potential interaction between solvent and noise exposure. The majority of the subjects were male (94.6%) and 35 years or older on the date of their first study audiogram (66%). Followed for an average of 3.2 years, 9.2% of the study subjects had hearing loss in at least one ear. Increasing age (odds ratio [OR] = 1.03 per year of age) and each year of follow-up time (OR = 1.23) were significantly associated with hearing loss. Low and moderate solvent exposures were not associated with hearing loss. Linear regression demonstrated that hearing loss was significantly associated with age at first study audiogram, length of follow-up time, and exposure to noise. Hearing decreased by 0.04 decibels for every decibel increase in noise level or by almost half a decibel (0.4 dB) for every 10 decibel increase in noise level. PMID- 24231417 TI - Road traffic noise, air pollution components and cardiovascular events. AB - Traffic noise and air pollution have been associated with cardiovascular health effects. Until date, only a limited amount of prospective epidemiological studies is available on long-term effects of road traffic noise and combustion related air pollution. This study investigates the relationship between road traffic noise and air pollution and hospital admissions for ischemic heart disease (IHD: International Classification of Diseases (ICD9) 410-414) or cerebrovascular disease (cerebrovascular event [CVE]: ICD9 430-438). We linked baseline questionnaire data to 13 years of follow-up on hospital admissions and road traffic noise and air pollution exposure, for a large random sample (N = 18,213) of inhabitants of the Eindhoven region, Netherlands. Subjects with cardiovascular event during follow-up on average had higher road traffic noise day, evening, night level (L den) and air pollution exposure at the home. After adjustment for confounders (age, sex, body mass index, smoking, education, exercise, marital status, alcohol use, work situation, financial difficulties), increased exposure did not exert a significant increased risk of hospital admission for IHD or cerebrovascular disease. Relative risks (RRs) for a 5 (th) to 95 (th) percentile interval increase were 1.03 (0.88-1.20) for L den; 1.04 (0.90-1.21) for particulate matter (PM 10 ); 1.05 (0.91-1.20) for elemental carbon (EC); and 1.12 (096-1.32) for nitrogen dioxide (NO 2 ) in the full model. While the risk estimate seemed highest for NO 2 , for a 5 (th) to 95 (th) percentile interval increase, expressed as RRs per 1 MUg/m 3 increases, hazard ratios seemed highest for EC (RR 1.04 [0.92-1.18]). In the subgroup of study participants with a history of cardiovascular disease, RR estimates seemed highest for noise exposure (1.19 [0.87-1.64] for L den); in the subgroup of elderly RR seemed highest for air pollution exposure (RR 1.24 [0.93-1.66] for NO 2 ). PMID- 24231419 TI - Qualitative and quantitative assessment of noise at moderate intensities on extra auditory system in adult rats. AB - Noise has long been realized as an environmental stress causing physiological, psychological and behavioral changes in humans. The aim of the present study was to determinate the effect of chronic noise at moderate intensities on both glandular and cardiac function and oxidative status. Our problem comes from working conditions in call centers where operators are responsible for making simple and repetitive tasks. One wishes to ascertain the effects of moderate sound levels on rats exposed to the same noise levels during similar periods to those experienced by call center operators. Male Wistar rats were exposed to 70 and 85 dB(A) to an octave-band noise (8-16 kHz) 6 h/day for 3 month. Corticosterone levels, oxidative status and functional exploration of adrenal and thyroid glands and cardiac tissue were determined. Exposure to long-term noise for different intensities (70 and 85 dB(A)) resulted in increased corticosterone levels, affected various parameters of the endocrine glands and cardiac function. Markers of oxidative stress (catalase, superoxide dismutase and lipid peroxidation) were increased. These results imply that long-term exposure to noise even at moderate levels may enhance physiological function related to neuroendocrine modulation and oxidative imbalance. In these data, the physiological changes occur during the different sounds suggests the concept of allostatic load or homeostatic response of the body. PMID- 24231418 TI - Does tinnitus "fill in" the silent gaps? AB - In the basic sciences, many researchers now use gap pre-pulse inhibition of the acoustic startle reflex (GPIAS) to determine if an animal has tinnitus after exposure to an ototoxic drug or intense noise. Tinnitus is assumed to be present if the silent gap in an ongoing narrow band noise (NBN) fails to suppress the startle reflex response evoked by an intense noise burst. The lack of gap pre pulse inhibition presumably occurs because tinnitus fills in the silent intervals in the background noise. To test the perceptual aspects of this hypothesis, we asked hearing impaired subjects with tinnitus if they could perceive 50 ms silent intervals presented in a NBN, which was located above, below or at the subject's tinnitus pitch. The same tests were performed on normal hearing subjects without tinnitus. All subjects, with and without tinnitus, could detect the 50 ms gaps. Thus, using the stimulus parameters similar to those employed in animal and human GPIAS studies, we found that the tinnitus percept does not fill in the silent interval in a perceptual gap detection task; however, these finding do not rule out the possibility that tinnitus interferes with pre-attentive filtering of sensory stimuli in the GPIAS sensorimotor gating paradigm. PMID- 24231420 TI - The prevalence of audiometric notches in adolescents in Germany: The Ohrkan study. AB - Although there is concern about increasing hearing loss in adolescents caused by leisure noise exposure, prevalence data are scarce. In an US study, about 16-17% of adolescents were affected by audiometric notches. To estimate the prevalence of audiometric notches in adolescents in Germany, baseline data of the cohort study Ohrkan, recruitment during the school years 2009/2010 and 2010/2011 were analyzed. All students in grade 9 visiting any school in the city of Regensburg were eligible for participation. Data was collected via standardized questionnaires from students and their parents. In addition, students were asked to visit the University Clinics of Regensburg for ear examination including a tympanogram and the determination of hearing thresholds in air conduction audiometry. The prevalence of audiometric notches was determined in students with normal tympanogram in both ears and complete audiometry data. Audiometric notches were defined according to criteria used to analyse US data. Overall, 2149 students (1158 girls, 991 boys mainly aged 15-16 years) of the 3846 eligible adolescents (56%) participated. Among the 1843 adolescents with complete audiometry and tympanometry data, the prevalence of audiometric notches was 2.4% (95% confidence interval 1.7-3.1%). We could not confirm the high prevalence of audiometric notches as reported in National Health and Nutrition Examination Surveys for adolescents in the US. Differences in prevalence might be at least partly due to methodical differences in audiometry. Even if empirical evidence is presently ambiguous, it is reasonable to educate young people about the potential risks of high leisure noise exposure. PMID- 24231421 TI - Comparison of sound propagation and perception of three types of backup alarms with regards to worker safety. AB - A technology of backup alarms based on the use of a broadband signal has recently gained popularity in many countries. In this study, the performance of this broadband technology is compared to that of a conventional tonal alarm and a multi-tone alarm from a worker-safety standpoint. Field measurements of sound pressure level patterns behind heavy vehicles were performed in real work environments and psychoacoustic measurements (sound detection thresholds, equal loudness, perceived urgency and sound localization) were carried out in the laboratory with human subjects. Compared with the conventional tonal alarm, the broadband alarm generates a much more uniform sound field behind vehicles, is easier to localize in space and is judged slighter louder at representative alarm levels. Slight advantages were found with the tonal alarm for sound detection and for perceived urgency at low levels, but these benefits observed in laboratory conditions would not overcome the detrimental effects associated with the large and abrupt variations in sound pressure levels (up to 15-20 dB within short distances) observed in the field behind vehicles for this alarm, which are significantly higher than those obtained with the broadband alarm. Performance with the multi-tone alarm generally fell between that of the tonal and broadband alarms on most measures. PMID- 24231422 TI - The cost of hypertension-related ill-health attributable to environmental noise. AB - Hypertension (HT) is associated with environmental noise exposure and is a risk factor for a range of health outcomes. The study aims were to identify key HT related health outcomes and to quantify and monetize the impact on health outcomes attributable to environmental noise-related HT. A reiterative literature review identified key HT related health outcomes and their quantitative links with HT. The health impact of increases in environmental noise above recommended daytime noise levels (55 dB[A]) were quantified in terms of quality adjusted life years and then monetized. A case study evaluated the cost of environmental noise, using published data on health risks and the number of people exposed to various bands of environmental noise levels in the United Kingdom (UK). Three health outcomes were selected based on the strength of evidence linking them with HT and their current impact on society: Acute myocardial infarction (AMI), stroke and dementia. In the UK population, an additional 542 cases of HT-related AMI, 788 cases of stroke and 1169 cases of dementia were expected per year due to daytime noise levels >=55 dB(A). The cost of these additional cases was valued at around L1.09 billion, with dementia accounting for 44%. The methodology is dependent on the availability and quality of published data and the resulting valuations reflect these limitations. The estimated intangible cost provides an insight into the scale of the health impacts and conversely the benefits that the implementation of policies to manage environmental noise may confer. PMID- 24231423 TI - Classroom acoustics and hearing ability as determinants for perceived social climate and intentions to stay at work. AB - Background noise and room acoustics may impede social interactions by interfering with oral communication and other cognitive processes. Accordingly, recent research in school environments has showed that social relationships with peers and teachers are described more negatively in rooms with long reverberation times (RT). The purpose of this study was to investigate how RT and hearing ability (i.e., hearing thresholds [HT] and distortion product oto-acoustic emissions) were associated with school teachers' perceptions of the social climate at work and their intentions to stay on the job. School teachers (n = 107) from 10 schools that worked in classrooms classified by acoustical experts as "short RT" (3 schools, mean RT 0.41-0.47 s), "medium RT" (3 schools, mean RT 0.50-0.53 s), and "long RT" (4 schools, mean RT 0.59-0.73 s) were examined. Teachers who worked in classrooms with long RT perceived their social climate to be more competitive, conflict laden, and less relaxed and comfortable. They were more doubtful about staying on the job. Even if the teachers were generally satisfied with their work the results suggest that the comfort at work may have been further improved by acoustical interventions that focus on reducing sound reflections in the classrooms. Yet, due the study design and the novelty of the findings the potential practical significance of our observations remains to be evaluated. PMID- 24231426 TI - Social, dietary and lifestyle factors associated with obesity among Bahraini adolescents. AB - The main purpose of this study was to explore some of the social, dietary and lifestyle factors that could be related to the risk of obesity among adolescents in Bahrain. A multistage stratified method was used to select secondary school students (15-18years old) from governmental schools in Bahrain. The total sample selected was 735 (339 males and 396 females). A pre-validated self-report questionnaire was used to obtain information on socio-demographics, food and the lifestyle habits of adolescents. Weight and height were taken and percentiles of Body Mass Index for age and gender were used to classify the adolescents as non obese and obese (overweight and obese), using NHANES-1 growth standard. In general, the prevalence of overweight and obesity was 29.5% and 36.8% among males and females, respectively. The risk of obesity was not consistent among male and female adolescents. Mothers' education was found to be a risk factor for obesity among both males and females (p=0.0167 and p=0.007, respectively). Bringing food from home to school (odds ratio (OR)=0.54, confidence interval (CI) 0.35-0.81) was protective factor for obesity among females but not among males. Fathers' education (p=0.0167), rank among siblings (p=0.009), place where breakfast is eaten (p=0.0398), eating between lunch and dinner (p=0.0152), fruit intake (p=0.042), sweet intake (p=0.0192), size of burger (p=0.002) and hours of watching television per day (p=0.004) were significantly associated with the risk of obesity among males, but not among females. Various social, dietary and lifestyle factors were found to contribute to obesity among adolescents in Bahrain. These factors should be considered in school health policy in the country. PMID- 24231424 TI - Dorsal and ventral streams: the distinct role of striatal subregions in the acquisition and performance of goal-directed actions. AB - Considerable evidence suggests that distinct neural processes mediate the acquisition and performance of goal-directed instrumental actions. Whereas a cortical-dorsomedial striatal circuit appears critical for the acquisition of goal-directed actions, a cortical-ventral striatal circuit appears to mediate instrumental performance, particularly the motivational control of performance. Here we review evidence that these distinct mechanisms of learning and performance constitute two distinct 'streams' controlling instrumental conditioning. From this perspective, the regulation of the interaction between these 'streams' becomes a matter of considerable importance. We describe evidence that the basolateral amygdala, which is heavily interconnected with both the dorsal and ventral subregions of the striatum, coordinates this interaction providing input to the final common path to action as a critical component of the limbic-motor interface. PMID- 24231425 TI - Prefrontal single-unit firing associated with deficient extinction in mice. AB - The neural circuitry mediating fear extinction has been increasingly well studied and delineated. The rodent infralimbic subregion (IL) of the ventromedial prefrontal cortex (vmPFC) has been found to promote extinction, whereas the prelimbic cortex (PL) demonstrates an opposing, pro-fear, function. Studies employing in vivo electrophysiological recordings have observed that while increased IL single-unit firing and bursting predicts robust extinction retrieval, increased PL firing can correlate with sustained fear and poor extinction. These relationships between single-unit firing and extinction do not hold under all experimental conditions, however. In the current study, we further investigated the relationship between vmPFC and PL single-unit firing and extinction using inbred mouse models of intact (C57BL/6J, B6) and deficient (129S1/SvImJ, S1) extinction strains. Simultaneous single-unit recordings were made in the PL and vmPFC (encompassing IL) as B6 and S1 mice performed extinction training and retrieval. Impaired extinction retrieval in S1 mice was associated with elevated PL single-unit firing, as compared to firing in extinguishing B6 mice, consistent with the hypothesized pro-fear contribution of PL. Analysis of local field potentials also revealed significantly higher gamma power in the PL of S1 than B6 mice during extinction training and retrieval. In the vmPFC, impaired extinction in S1 mice was also associated with exaggerated single-unit firing, relative to B6 mice. This is in apparent contradiction to evidence that IL activity promotes extinction, but could reflect a (failed) compensatory effort by the vmPFC to mitigate fear-promoting activity in other regions, such as the PL or amygdala. In support of this hypothesis, augmenting IL activity via direct infusion of the GABAA receptor antagonist picrotoxin rescued impaired extinction retrieval in S1 mice. Chronic fluoxetine treatment produced modest reductions in fear during extinction retrieval and increased the number of Zif268-labeled cells in layer II of IL, but failed to increase vmPFC single-unit firing. Collectively, these findings further support the important contribution these cortical regions play in determining the balance between robust extinction on the one hand, and sustained fear on the other. Elucidating the precise nature of these roles could help inform understanding of the pathophysiology of fear-related anxiety disorders. PMID- 24231427 TI - Consumer fears and familiarity of processed food. The value of information provided by the FTNS. AB - Food choice and consumption behaviour are influenced by many interacting factors. In this paper we present an empirical effort to enhance understanding of the neophobia-neophilia forces affecting food choice. Starting from the analysis of consumer preferences for some of the most familiar highly processed foods, namely fat-reduced, functional (enriched drinks and yogurt) and ready-to-eat frozen food, our study investigates the role of traditional demographic variables vs attitudes to new food technologies in predicting the consumption behaviour of a sample of Italians buying such products. Consumer attitudes toward food technologies were collected by means of the Food Technology Neophobia Scale (FTNS). Moreover, this paper explicitly analyses the value of the information provided by the FTNS. Underlying the research is the hypothesis that the FTNS may contribute to provide a comprehensive picture of the driving forces behind consumers' behavioural responses towards processed foods which are the end-result of mature technologies. The four FTNS components, once measured and used independently, help clarify the influence on food choices of each neophobia neophilia force (risk perception and novelty seeking, media influence, own health and environmental concerns) into a single, comprehensive framework. PMID- 24231428 TI - The role of personal values in Chinese consumers' food consumption decisions. A case study of healthy drinks. AB - Differences in culture, language, and behavior between Chinese and Western consumers make entering the Chinese market a challenge. Chinese consumers may desire similar product features (e.g. brand name, quality, and flavor) to Western consumers but the value that consumers attach to the same product may differ cross-nationally. Besides values, an understanding of desired product attributes and the consequences linking to these values is also important. To the authors' knowledge, there is no published scientific research that investigates how personal values influence Chinese consumers' food consumption decisions. The aim of this research was to identify the links among product attributes, consequences of these attributes, and personal values associated with healthy drink consumption decisions within the Chinese market. Specifically, this research employed means-end chain theory and used association pattern technique (APT) as the main data collection technique to identify these links. Focus groups (n=6) were held in Hangzhou, China to identify the important attributes and consequences involved in the consumption decisions of healthy drinks. These attributes and consequences along with Schwartz's 10 basic values were used to construct the matrices included in the APT survey. A total of 600 APT surveys were administered in six different companies in Hangzhou, with 570 returned. Construction of the hierarchical value map (HVM) identified four of Schwartz's personal values influencing Chinese consumers' healthy drink consumption decisions: security, hedonism, benevolence, and self-direction. Food safety was the foremost concern for Chinese consumers when choosing healthy drinks. Chinese consumers also sought a good tasting and nutritious drink that was good value for money. Results from this study provide food marketers with an in-depth understanding of Chinese consumers' healthy drink consumption decisions. Implications and recommendations are provided that will assist food marketers to effectively enact marketing strategies in China. PMID- 24231429 TI - Rationale and prospects of mesenchymal stem cell therapy for liver transplantation. AB - PURPOSE OF REVIEW: Despite their potential to supplement the donor organ pool, expanded donor criteria grafts are associated with an elevated risk of graft failure and increased early mortality. Likewise, attempts to promote operational graft tolerance through conventional immunosuppressive therapy have demonstrated significant safety-related drawbacks. Because of their potent regenerative and immunomodulative potential, adjunct mesenchymal stem cell (MSC) therapy represents an innovative approach to both of these clinical problems. RECENT FINDINGS: Recent studies have begun to delineate the benefit and mechanisms of short-term therapy combining MSCs and low-dose immunosuppressive drugs in promoting graft acceptance and potentially regeneration. SUMMARY: The current review presents our rationale for the first-in-man clinical trial in liver transplantation utilizing a mesenchymal cell product (MultiStem, Athersys, Cleveland, Ohio, USA). The long-term objective of this program is to safely minimize the dose of complementary immunosuppressive drugs while achieving long term allograft survival and operational tolerance. The use of adjunct cellular therapy as a means of reducing long-term pharmacotherapy would represent a major advancement in the field of liver transplantation. PMID- 24231430 TI - Differential functional rescue of Lys(513) and Lys(516) processing mutants of MRP1 (ABCC1) by chemical chaperones reveals different domain-domain interactions of the transporter. AB - Multidrug resistance protein 1 (MRP1) extrudes drugs as well as pharmacologically and physiologically important organic anions across the plasma membrane in an ATP dependent manner. We previously showed that Ala substitutions of Lys(513) and Lys(516) in the cytoplasmic loop (CL5) connecting transmembrane helix 9 (TM9) to TM10 cause misfolding of MRP1, abrogating its expression at the plasma membrane in transfected human embryonic kidney (HEK) cells. Exposure of HEK cells to the chemical chaperones glycerol, DMSO, polyethylene glycol (PEG) and 4-aminobutyric acid (4-PBA) improved levels of K513A to wild-type MRP1 levels but transport activity was only fully restored by 4-PBA or DMSO treatments. Tryptic fragmentation patterns and conformation-dependent antibody immunoreactivity of the transport-deficient PEG- and glycerol-rescued K513A proteins indicated that the second nucleotide binding domain (NBD2) had adopted a more open conformation than in wild-type MRP1. This structural change was accompanied by differences in ATP binding and hydrolysis but no changes in substrate Km. In contrast to K513A, K516A levels in HEK cells were not significantly enhanced by chemical chaperones. In more permissive insect cells, however, K516A levels were comparable to wild type MRP1. Nevertheless, organic anion transport by K516A in insect cell membranes was reduced by >80% due to reduced substrate Km. Tryptic fragmentation patterns indicated a more open conformation of the third membrane spanning domain of MRP1. Thus, despite their close proximity to one another in CL5, Lys(513) and Lys(516) participate in different interdomain interactions crucial for the proper folding and assembly of MRP1. PMID- 24231431 TI - Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma. AB - Lymphomas grow as dense aggregates in patients, but whether this spatial organization affects lymphoma cell biology is unknown. We grew follicular lymphoma (FL) cells in vitro as multicellular aggregates of lymphoma cells to investigate this question. Gene expression analysis revealed that 612 genes were differentially expressed when cells grew in multicellular aggregates of lymphoma cells rather than in suspension. These genes correspond to several GO biological processes, such as hypoxia, activation of NF-kappaB pathway, and negative regulation of cell cycle, a gene signature also found in the transcriptomes from FL biopsies. Pimonidazole staining, HIF-1A accumulation, and VEGFA release confirmed that cells in multicellular aggregates of lymphoma cells actually respond to hypoxia. In adaptation to such conditions, they also displayed an activated NF-kappaB pathway and a quiescent status far more frequently than in suspension. When cultured in three dimensions, FL cells display resistance to doxorubicin and bendamustine, two drugs largely used in FL therapy, compared to FL cultured in suspension. Finally, multicellular aggregates of lymphoma cells were also found to be less sensitive to purified natural killer cells. To conclude, our study shows that in FL, spatial organization results in dramatic changes in FL biology, including gene expression, proliferation, drug resistance, and immune escape. PMID- 24231432 TI - Developing stem cell therapeutics for the heart also requires targeting non myocytes. PMID- 24231433 TI - Improving the value of fitness testing for football. AB - One of the challenges for sports scientists working in football is to balance the needs for routine fitness testing with daily fatigue and well-being monitoring to best manage the physical preparation of players. In this commentary, the authors examine contemporary issues of fitness testing in football to identify ways of improving the value of routine testing and monitoring. A testing program must be well planned and organized to ensure that the results are useful. Different tests can be employed for younger and older players. A rigorous approach to analysis and interpretation of results is desirable, and database management must address both short- and long-term requirements of players, staff, and programs. PMID- 24231434 TI - Changes in the cutting efficiency of different types of dental diamond rotary instrument with repeated cuts and disinfection. AB - STATEMENT OF PROBLEM: Cutting efficiency is one of the most important factors to consider when a specific dental diamond rotary instrument is selected. However, the selection of a dental diamond rotary instrument is based on clinical experience rather than any scientific evidence. PURPOSE: The purpose of this study was to identify how the cutting efficiency of different types of dental diamond rotary instrument changed with repeated cuts and disinfection. MATERIAL AND METHODS: Four types of diamond rotary instrument from 2 dental manufacturers (Shofu, Jin Dental) were investigated with a high-speed air-turbine handpiece. The groups were as follows: S cham group (n=10): chamfer design from Shofu; J cham group (n=10): chamfer design from Jin Dental; S thin group (n=10): thin tapered design from Shofu; J thin group (n=10): thin tapered design from Jin Dental. Changes in the cutting efficiency of diamond rotary instruments on glass ceramic blocks were measured after repeated cuts. Changes in cutting efficiency also were measured for 30 diamond rotary instruments, the same type as those used in group J cham after disinfection with ethylene oxide gas, immersion in solution, or autoclaving. One-way ANOVA, 2-way ANOVA, and repeated-measures ANOVA were used to identify differences in cutting efficiency, in total cutting efficiency, and change trend in cutting efficiency (alpha=.05). The Tukey honestly significant difference method was used for the post hoc tests. The principal metal components of the diamond rotary instruments were detected with x ray spectrometry. RESULTS: The mean (standard deviation [SD]) total cutting efficiency after 10 cuts in the 4 groups was in the following order: J cham group (0.210 +/- 0.064 g/min) > S cham group (0.170 +/- 0.064 g/min) > J thin group (0.130 +/- 0.042 g/min) > S thin group (0.010 +/- 0.040 g/min) (P<.05).The decrease in the cutting efficiency was greatest after the first cut. The cutting efficiency was not influenced by repeated disinfection. CONCLUSION: The cutting efficiencies of diamond rotary instruments with different designs and particle sizes showed a decreasing trend after repeated cuts but did not show any change after various disinfecting procedures. PMID- 24231435 TI - Conversion of an existing metal ceramic crown to an interim restoration and nonfunctional loading of a single implant in the maxillary esthetic zone: A clinical report. AB - Implant placement and immediate placement of an interim restoration can be a safe therapeutic approach with high survival rates. The technique is often used in the anterior esthetic area because of the better preservation of the periimplant soft tissue contours. Traditionally this procedure involves the fabrication of an acrylic resin implant-supported interim restoration. This clinical report describes the modification of an existing metal ceramic crown to be used as an implant-supported interim restoration for immediate nonfunctional loading to achieve an improved esthetic result and optimal support of the adjacent soft tissues. PMID- 24231436 TI - Higher revision and complication rates following total hip arthroplasty in patients with inflammatory bowel disease. AB - The purpose of this study was to compare the clinical outcomes of total hip arthroplasty in patients with and without inflammatory bowel disease (IBD). Between 2001 and 2010, all total hip arthroplasties performed at a single institution were reviewed to identify patients who had IBD. There were 23 total hip arthroplasties in the study group, which were matched in a 1:3 ratio to 69 additional hips. At a mean follow-up of 49 months (range, 24-96 months), patients with IBD had an overall significantly lower survivorship of 87% (n = 3 revisions), compared to 98.5% (n = 1 revision) in the matched group who had a mean follow-up of 47 months (range, 24-94 months). In addition, there were significantly higher major complications in the study group (5 patients) compared to the matched group (2 patients). These results indicate that patients with IBD had an overall higher revision and complication rate. PMID- 24231437 TI - Comparison of acetabular shell position using patient specific instruments vs. standard surgical instruments: a randomized clinical trial. AB - Total hip arthroplasty (THA) survivorship relies largely upon appropriate acetabular cup placement. The purpose of this prospective randomized controlled trial was to determine whether the use of a preoperative 3D planning software in combination with patient specific instrumentation (PSI) results in improved cup placement compared with traditional techniques. Thirty-six THA patients were randomized into standard (STD) or PSI technique. Standard approach was completed using traditional techniques, while PSI cases were planned and customized surgical instruments were manufactured. Postoperative CT scans were used to compare planned to actual results. Differences found between planned and actual anteversion were -0.2 degrees +/- 6.9 degrees (PSI) and -6.9 degrees +/-8.9 degrees (STD) (P = 0.018). Use of 3D preoperative planning along with PSIs resulted in significantly greater anteversion accuracy than traditional planning and instrumentation. PMID- 24231438 TI - Treatment of failed allograft prosthesis composites used for hip arthroplasty in the setting of severe proximal femoral bone defects. AB - This study assessed failures of allograft prosthesis composites (APC) and revisions with a new APC. Twenty-one patients with failed APC's after revision hip arthroplasty with severe proximal femoral bone loss underwent revision with a new APC. Causes of failure were aseptic loosening (18 patients), infection (3 patients). Of these 21 APC revisions, two patients failed (after 60, 156 months). The 5 and 10 year survival rates were 83.5% (95% CI, 79-100%, number at risk 12 and 6 accordingly). In addition, two patients had non-union at the host-allograft bone junction and were augmented with bone autograft and plate. These results suggest that failed APCs may be revised to a new APC with a predictable outcome. PMID- 24231439 TI - Update on immunizations for healthcare personnel in the United States. AB - Healthcare personnel (HCP) play a pivotal role in the transmission of contagious pathogens in the healthcare setting, and HCP are themselves at risk for infection with such pathogens due to the nature of their occupation. Many practices are important in order to reduce infection transmission, including HCP immunization. Unfortunately, HCP immunization rates in the United States (U.S.) have not reached recommended levels, so new strategies are being used to improve HCP coverage, including mandatory immunization and the use of immunization rates as measures of quality and safety. This article will review current practices, policies, and issues surrounding HCP immunization in the U.S. PMID- 24231441 TI - Dynamic stability and steering control following a sport-induced concussion. AB - Loss of balance control is one of the cardinal symptoms following a concussion; however, the ability to detect the duration of these balance impairments seems to largely depend on task type and complexity. Typical balance assessment tools are simplistic and do not challenge dynamic balance control. Changing direction represents an internal perturbation that challenges the balance control system. The purpose of this study was to examine the effects of a concussion on dynamic stability and steering control. Nine male intercollegiate North American football players who experienced a concussion (CONC) were tested during the symptomatic phase (acute) and again once they had been cleared to return to play (RTP) while the controls (age- and position-matched teammates) were tested at a single time point coinciding with the acute phase testing of their matched injured player. All participants performed a steering task, requiring them to walk straight or turn in the direction of a visual cue located either 60 degrees or 45 degrees to the left or right of the centre line. CONC demonstrated increased swing time variability, segmental re-orientation variability, and the amount of time it took the centre of mass to reach the minimum lateral dynamic stability margin. These results suggest that CONC were more unstable and adopted a conservative gait strategy. Differences in the variability measures persisted even after the athlete was cleared to RTP. Overall, the findings reveal that intercollegiate football players with concussions have difficulty controlling temporal characteristics of gait, which cause dynamic instability to persist even at RTP. PMID- 24231440 TI - Comparison of prophylactic and therapeutic immunisation with an ErbB-2 (HER2) fusion protein and immunoglobulin V-gene repertoire analysis in a transgenic mouse model of spontaneous breast cancer. AB - ErbB-2 is associated with several solid tumours of which breast cancer is the commonest cancer in women worldwide. Though anti-ErbB-2 antibody appears to play a significant role in prevention and therapy, naturally occurring anti-ErbB-2 antibody associated with the cleaved ectodomain of overexpressed ErbB-2 self antigen is detectable in patients. It is therefore essential to understand the course of antibody mediated protection during disease progression. 100% of FVB/N(neu) mice expressing mutated, constitutively active ErbB-2 develop mammary carcinoma. It has been shown that vaccination with ErbB-2 associated with a T helper cell epitope P30 can offer protection against transplantable tumour but it is unclear whether the same vaccine protects against naturally developing tumour. We have analysed the course of the disease following prophylactic, and therapeutic vaccination in this spontaneous, eutopic mammary carcinoma model that more closely resembles the human disease. 100% protection against tumour development was observed subsequent to prophylactic immunisation but disease progression was unaffected by therapeutic vaccination. The antibody response exhibited restricted expansion of the Immunoglobulin (Ig) variable (V)-gene repertoire by ErbB-2 specific B cells compared with the non-antigen specific B cell pool and control mice. The serum antibody profile was similar in therapeutically injected mice without any effect on tumour burden. PMID- 24231442 TI - Electronic transport in patterned graphene nanoroads. AB - Graphane, hydrogenated graphene, can be patterned into electronic devices by selectively removing hydrogen atoms. The most simple of such devices is the so called nanoroad, analogous to the graphene nanoribbon, where confinement-and the opening of a gap-is obtained without the need for breaking the carbon bonds. In this work we address the electronic transport properties of such systems considering different hydrogen impurities within the conduction channel. We show, using a combination of density functional theory and non-equilibrium Green's functions, that hydrogen leads to significant changes in the transport properties and in some cases to current polarization. PMID- 24231443 TI - TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression. AB - OBJECTIVE: Enthesitis-related arthritis (ERA) is an inflammatory disease of childhood that lacks autoantibodies. Overexpression of surface-expressed Toll like receptors (TLRs) has been found in ERA. Myeloid-related proteins (MRPs) 8 and 14 are calcium binding proteins that act as an endogenous ligand of TLR4. MRP8/14 levels are elevated in patients with systemic-onset arthritis. Thus we studied the role of MRP8/14 in ERA. METHODS: The study enrolled patients with ERA. Plasma and SF levels of MRP8/14 were measured by ELISA and TLR4 expression on peripheral blood and SF monocytes was measured by two-colour flow cytometry. Control plasma samples were collected from 48 blood bank donors. RESULTS: Of the 69 patients, 67 were male, with a mean age of 15.2 (s.d. 2.7) years and a disease duration of 5 (s.d. 3) years. Median plasma levels of MRP8/14 were higher in patients (10 862.3 ng/ml) than controls (4426.1 ng/ml, P < 0.0001). Patients with active disease (11 669.5 ng/ml) had higher levels as compared with inactive disease (4421.8 ng/ml, P < 0.0001). Plasma MRP8/14 levels decreased on follow-up after 3 months only in patients who responded to treatment (P = 0.012). MRP8/14 levels were negatively correlated with the frequency of CD14(+)TLR4(+) cells (r = -0.372, P = 0.02). MRP8/14 levels were higher in SF as compared with plasma (15 858.45 ng/ml, P = 0.024). The frequency of CD14(+)TLR4(+) cells was higher in SF as compared with peripheral blood. CONCLUSION: MRP8/14 levels are increased in the plasma of ERA patients and are higher in those with active disease and the levels decrease in patients who respond to treatment, suggesting that it may be a good biomarker during follow-up. PMID- 24231444 TI - Ultrasound evaluation of hand, wrist and foot joint synovitis in systemic lupus erythematosus. AB - OBJECTIVES: To assess the prevalence and severity of inflammatory abnormalities of the hand, wrist and foot joints in SLE patients by US and to correlate them with clinical, laboratory and disease activity score parameters. METHODS: Sixty two consecutive SLE patients were enrolled in the present study and underwent clinical evaluation, laboratory tests and bilateral high-resolution US of the hand, wrist and foot joints. Joint effusion (JE), synovial hypertrophy (SH) and local pathological vascularization [power Doppler (PD)] were evaluated according to both a dichotomous score and a semi-quantitative (0-3) grading system. In addition, a global US score was calculated by summing the values given to each elementary lesion for every single joint and every joint group. US findings were correlated with physical examination, serological parameters (CRP, ANA, anti dsDNA, ENA, aPL, C3 and C4 serum levels) and disease activity indexes (SLEDAI-2K, ECLAM). RESULTS: US detected inflammatory joint abnormalities in 54/62 patients (87.1%); 72.6% presented involvement of the MTP joints, 46.7% the MCP joints, 19.3% the PIP joints and 53% the wrists. A total of 1984 joints were examined highlighting JE in 19.1% of cases, SH in 6.9% and positive PD in 1.1%. The global US inflammatory score had a mean value of 10.9 (s.d. 15.2). No correlations were found between US findings and SLE disease activity parameters. CONCLUSION: US demonstrated a high prevalence of inflammatory joint abnormalities in SLE that were also present in asymptomatic patients. Interestingly, the foot joints were the most frequently involved. US is a valuable tool for detecting subclinical synovitis in SLE. PMID- 24231445 TI - Review: the ADAM metalloproteinases - novel regulators of trophoblast invasion? AB - During pregnancy, the extravillous trophoblast (EVT) invades the maternal decidua and remodels spiral arteries reaching as far as the inner third of the myometrium. This process is mandatory to a successful pregnancy since EVTs regulate spiral artery remodeling to achieve maximal vasodilation and thus an adequate nutrient supply to the embryo or communicate with maternal leukocyte populations to guarantee acceptance of the allogeneic conceptus. To achieve this, EVTs undergo a remarkable and unique differentiation process, which yields different phenotypes such as proliferative cell column trophoblasts or growth arrested, invasive interstitial or endovascular cytotrophoblasts. Matrix metalloproteinases have long been seen as imperative to trophoblast invasion because of their ability to degrade extracellular matrix and therefore allow cellular movement in foreign tissues. However, global gene expression analysis reveals that EVTs also express various members of distintegrin and metalloproteinases (ADAMs). These proteases are associated with the process of proteolytic shedding and activation of surface proteins including growth factors, cytokines, receptors and their ligands rather than extracellular matrix breakdown. While ADAM12 has been associated with chromosomal abnormalities as well as preeclampsia or intrauterine fetal growth restriction, the function of ADAMs in trophoblasts remains elusive. In this article, we review the diverse invasive trophoblast phenotypes, EVT-associated protease systems and related open questions. In addition, we examine recent information about relevant ADAM members and their putative implications for EVT biology. PMID- 24231446 TI - Editorial. Trophoblast Research. PMID- 24231447 TI - Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor induced endothelin-1 upregulation in human microvascular endothelial cells. AB - INTRODUCTION: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (alpha2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and alpha2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC 1). METHODS: HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and alpha2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. RESULTS: ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10 1000 ng/mL) or alpha2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while alpha2M did not affect the VEGF-induced ET-1 expression. CONCLUSIONS: sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, alpha2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form alpha2M-VEGF have a biological action involved in the pathophysiology of preeclampsia. PMID- 24231448 TI - Prediction and clinical relevance of pathologic patterns of injury associated with chorioamnionitis. AB - The aim of the present study was to evaluate both prediction and clinical relevance of different patterns of injury associated with chorioamnionitis. Pathologic examination of placentas and umbilical cords were performed in 45 pregnant women who had had diagnostic amniocentesis for suspected intraamniotic infection. A positive correlation was noted between leukocyte account in amniotic fluid and the level of maternal injury (r = 0.46, p = 0.04). The levels of amniotic fluid glucose were significantly reduced in cases of fetal infection (2 mg/dL (1-16 mg/dL)) vs. (20.50 mg/dL (11-29 mg/dL)) (p = 0.03). PMID- 24231449 TI - Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL resistant human glioma U373MG cells. AB - AIMS: Neobavaisoflavone (NBIF), an isoflavone isolated from Psoralea corylifolia (Leguminosae), has striking anti-inflammatory and anti-cancer effects. NBIF inhibits the proliferation of prostate cancer in vitro and in vivo. MAIN METHODS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key endogenous molecule that selectively induces apoptosis in cancer cells with little or no toxicity in normal cells. However, some cancer cells, including U373MG cells, are resistant to TRAIL-mediated apoptosis. We demonstrated that the cell viability, migration and invasion assay were used in U373MG glioma cells. KEY FINDINGS: In this study, we found that NBIF sensitizes human U373MG glioma cells to TRAIL-mediated apoptosis. Co-treatment of TRAIL and NBIF effectively induced Bid cleavage and activated caspases 3, 8, and 9. Importantly, DR5 expression was upregulated by NBIF. We also observed that the combination NBIF and TRAIL increased expression of BAX. We further demonstrate that NBIF induced TRAIL-mediated apoptosis in human glioma cells by suppressing migration and invasion, and by inhibiting anoikis resistance. SIGNIFICANCE: Taken together, our results suggest that NBIF reduces the resistance of cancer cells to TRAIL and that the combination of NBIF and TRAIL may be a new therapeutic strategy for treating TRAIL-resistant glioma cells. PMID- 24231451 TI - A small cog in a big wheel: PIK3CA mutations in colorectal cancer. PMID- 24231450 TI - Behavioral pharmacology of designer cathinones: a review of the preclinical literature. AB - "Bath salts" is one street name for a family of synthetic cathinones that display pharmacological effects resembling cocaine and commonly abused amphetamines. Despite extensive legislation aimed at the criminalization of bath salts, several designer cathinones are gaining a foothold in the illicit drug scene; for example, in the United Kingdom, mephedrone (4-methylmethcathinone, MEPH) is highly popular among drug abusers whereas, in the United States, MDPV (methylenedioxypyrovalerone) and methylone are highly prevalent. To date, knowledge about the hazards of designer cathinones is based mostly on hospital reports and anecdotal evidence derived from online surveys. Despite the paucity of preclinical studies directed toward designer cathinones, a number of invaluable findings arising from those studies are enabling scientists to develop their neuropharmacological profiles. Despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce different behavioral effects, including unique effects on locomotor activity, learning, anxiety, thermoregulation, and abuse liability. The present review will discuss the behavioral effects of MEPH, MDPV, and methylone and compare those effects to established psychostimulant drugs. The rise in the use of designer cathinones in the United States and abroad justifies further investigations into these compounds, both for a greater understanding of the danger that "bath salts" pose to the public, and to provide insight into replacement cathinones as they emerge onto the market. PMID- 24231452 TI - Breast cancer risk in opposite-sexed twins: influence of birth weight and co-twin birth weight. AB - Most, but not all, studies report a positive association between birth weight, as an indirect marker of prenatal hormone exposure, and offspring breast cancer risk, particularly premenopausal breast cancer. Females from opposite-sexed twin pairs may also be prenatally exposed to androgens from their twin brothers. A Swedish study of opposite-sexed twins with a small sample size found a very strong positive association between female birth weight and breast cancer risk. In this case-control study, nested within a cohort of female opposite-sexed twins, we included 543 breast cancer case subjects diagnosed in the period from 1972 to 2008 and 2715 matched control subjects. Conditional logistic regression estimated the breast cancer risk associated with birth weight and other birth characteristics, including gestational age and co-twin birth weight. All statistical tests were two-sided. There was no association between birth weight (odds ratio = 1.01; 95% confidence interval = 0.70 to 1.46) or twin brother's birth weight and risk of breast cancer, which suggests the previously reported strong positive association may have been a chance finding. PMID- 24231453 TI - Racial disparity in consultation, treatment, and the impact on survival in metastatic colorectal cancer. AB - BACKGROUND: Black patients with metastatic colorectal cancer have inferior survival compared to white patients. The purpose of this study was to examine disparity in specialist consultation and multimodality treatment and the impact that treatment inequality has on survival. METHODS: We identified 9935 non Hispanic white and 1281 black patients with stage IV colorectal cancer aged 66 years and older from the Surveillance, Epidemiology, and End Results (SEER) Medicare linked database. Logistic regression models identified race-based differences in consultation rates and subsequent treatment with surgery, chemotherapy, or radiation. Multivariable Cox regression models identified potential factors that explain race-based survival differences. All statistical tests were two-sided. RESULTS: Black patients had lower rates of consultation with surgery, medical oncology, and radiation oncology. Among patients seen in consultation, black patients received less surgery directed at the primary tumor, liver- or lung-directed surgery, chemotherapy, and radiotherapy. Unadjusted survival analysis found a 15% higher chance of dying for black patients compared with white patients (hazard ratio [HR] = 1.15; 95% confidence interval (CI) = 1.08 to 1.22; P < .001). Adjustment for patient, tumor, and demographic variables marginally reduced the risk of death (HR = 1.08; 95% CI = 1.01 to 1.15; P = .03). After adjustment for differences in treatment, the increased risk of death for black patients disappeared. CONCLUSIONS: Our study shows racial disparity in specialist consultation as well as subsequent treatment with multimodality therapy for metastatic colorectal cancer, and it suggests that inferior survival for black patients may stem from this treatment disparity. Further research into the underlying causes of this inequality will improve access to treatment and survival in metastatic colorectal cancer. PMID- 24231455 TI - Poor long-term stability of the Corvita abdominal stentgraft. AB - INTRODUCTION: The endovascular treatment of abdominal aortic aneurysms was introduced in the early 1990s, with different generations of devices using various options for either the stent skeleton or the membrane. REPORT: Corvita generated one of these devices using braided stainless steel and a porous spun polycarbonate urethane membrane. DISCUSSION: In this report, we describe a case involving Corvita stentgraft explantation for complete aneurysm reperfusion after 13 years, demonstrating major degradation of the polyurethane membrane. PMID- 24231456 TI - Validation and diagnostic utility of the dementia rating scale in a mixed dementia population. AB - The Dementia Severity Rating Scale (DSRS), a previously validated caregiver-based measure assessing dementia severity, was recently revised to improve clarity. Our study aims included: (1) identifying the DSRS factor structure, (2) examining the relation between neuropsychological measures, the Mini-Mental State Examination, and clinical diagnoses with the DSRS, and (3) determining the clinical utility of the DSRS in a mixed clinical sample. A total of 270 veterans were referred to a cognitive disorders clinic at a VA medical center and completed neuropsychological, affective, and cognitive screening measures. Caregivers completed the DSRS. Principal components analysis identified a 2-factor solution. After controlling for age and education, memory and language were related to the Cognitive factor, whereas attention, processing speed, visuospatial processing, and executive functioning were related to both Cognitive and Self-Care factors. Neither factors correlated with depression. The total DSRS score was able to differentiate patients by the Mini-Mental State Examination scores and diagnoses of mild cognitive impairment and dementia (mixed vascular Alzheimer, vascular dementia, and Alzheimer disease). A cut-score >15 was optimal for detecting dementia in a mixed clinical sample (sensitivity=0.41, specificity=0.79), with a posttest probability of 74%. This study suggests that the DSRS improves detection of dementia and requires minimal effort to implement. PMID- 24231457 TI - Impact of the urgent care telephone service NHS 111 pilot sites: a controlled before and after study. AB - OBJECTIVES: To measure the impact of the urgent care telephone service NHS 111 on the emergency and urgent care system. DESIGN: Controlled before and after study using routine data. SETTING: Four pilot sites and three control sites covering a total population of 3.6 million in England, UK. PARTICIPANTS AND DATA: Routine data on 36 months of use of emergency ambulance service calls and incidents, emergency department attendances, urgent care contacts (general practice (GP) out of hours, walk in and urgent care centres) and calls to the telephone triage service NHS direct. INTERVENTION: NHS 111, a new 24 h 7 day a week telephone service for non-emergency health problems, operated by trained non-clinical call handlers with clinical support from nurse advisors, using NHS Pathways software to triage calls to different services and home care. MAIN OUTCOMES: Changes in use of emergency and urgent care services. RESULTS: NHS 111 triaged 277 163 calls in the first year of operation for a population of 1.8 million. There was no change overall in emergency ambulance calls, emergency department attendances or urgent care use. There was a 19.3% reduction in calls to NHS Direct (95% CI 24.6% to -14.0%) and a 2.9% increase in emergency ambulance incidents (95% CI 1.0% to 4.8%). There was an increase in activity overall in the emergency and urgent care system in each site ranging 4.7-12%/month and this remained when assuming that NHS 111 will eventually take all NHS Direct and GP out of hours calls. CONCLUSIONS: In its first year of operation in four pilot sites NHS 111 did not deliver the expected system benefits of reducing calls to the 999 ambulance service or shifting patients to urgent rather than emergency care. There is potential that this type of service increases overall demand for urgent care. PMID- 24231454 TI - Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. AB - BACKGROUND: Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. METHODS: We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. RESULTS: Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P(interaction) > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P(interaction) > .16). CONCLUSIONS: Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. PMID- 24231458 TI - Pain management for chronic musculoskeletal conditions: the development of an evidence-based and theory-informed pain self-management course. AB - OBJECTIVE: To devise and test a self-management course for chronic pain patients based on evidence and underpinned by theory using the Medical Research Council (MRC) framework for developing complex interventions. DESIGN: We used a mixed method approach. We conducted a systematic review of the effectiveness of components and characteristics of pain management courses. We then interviewed chronic pain patients who had attended pain and self-management courses. Behavioural change theories were mapped onto our findings and used to design the intervention. We then conducted a feasibility study to test the intervention. SETTING: Primary care in the inner city of London, UK. PARTICIPANTS: Adults (18 years or older) with chronic musculoskeletal pain. OUTCOMES: Related disability, quality of life, coping, depression, anxiety, social integration and healthcare resource use. RESULTS: The systematic reviews indicated that group-based courses with joint lay and healthcare professional leadership and that included a psychological component of short duration (<8 weeks) showed considerable promise. The qualitative research indicated that participants liked relaxation, valued social interaction and course location, and that timing and good tutoring were important determinants of attendance. We used behavioural change theories (social learning theory and cognitive behaviour approaches (CBA)) to inform course content. The course addressed: understanding and accepting pain, mood and pain, unhelpful thoughts and behaviour, problem solving, goal setting, action planning, movement, relaxation and social integration/reactivation. Attendance was 85%; we modified the recruitment of patients, the course and the training of facilitators as a result of testing. CONCLUSIONS: The MRC guidelines were helpful in developing this intervention. It was possible to train both lay and non psychologists to facilitate the courses and deliver CBA. The course was feasible and well received. PMID- 24231459 TI - What happens when patients know more than their doctors? Experiences of health interactions after diabetes patient education: a qualitative patient-led study. AB - OBJECTIVE: To explore the impact of patient education on the lives of people with diabetes, including the effect on interactions with doctors and other healthcare professionals. DESIGN: Qualitative user-led study using longitudinal interviews and 146 h of participant observation. Data were analysed using a narrative approach. PARTICIPANTS: 21 patients with type 1 diabetes, those either about to attend a patient education course or those who had completed the course in the previous 10 years. SETTING: Established patient education centres in three UK teaching hospitals teaching the Dose Adjustment for Normal Eating (DAFNE) course. RESULTS: Both postcourse and several years later, most participants spoke of the experience of taking part in education as life-changingly positive. It helped them understand how to gain control over a very complex disease and freed them from dependence on medical advice and restrictive regimes. However, interactions within the health system following patient education could be fraught. Participants emerged from the course with greater condition-specific knowledge than many of the healthcare professionals they encountered. When these professionals did not understand what their patients were trying to do and were uncomfortable trusting their expertise, there could be serious consequences for these patients' ability to continue effective self-management. CONCLUSIONS: Patients who have in-depth knowledge of their condition encounter problems when their expertise is seen as inappropriate in standard healthcare interactions, and expertise taught to patients in one branch of medicine can be considered non compliant by those who are not specialists in that field. Although patient education can give people confidence in their own self-management skills, it cannot solve the power imbalance that remains when a generalist healthcare professional, however well meaning, blocks access to medication and supplies needed to manage chronic diseases successfully. There is a role for those involved in primary and hospital care, including those supporting and training healthcare professionals, to recognise these problems and find ways to acknowledge and respect chronic patients' biomedical and practical expertise. PMID- 24231460 TI - Predictive role of C reactive protein in stroke recurrence after cardioembolic stroke: the Fukuoka Stroke Registry. AB - OBJECTIVES: We investigated the clinical characteristics of patients with stroke recurrence in the first year after cardioembolic stroke, and determined the predictors associated with recurrence. DESIGN: A prospective cohort study. SETTING: Multicentre study at the Fukuoka prefecture in Japan. PARTICIPANTS: We enroled 2084 consecutive patients who were hospitalised in stroke centres within 7 days of onset from June 2007 to October 2009. The clinical characteristics of patients were assessed on admission, and the clinical course of all patients was followed for 1 year. RESULTS: Of all patients, 425 (234 men, 76+/-11 years of age) had cardioembolic stroke and were included in this study. Fifty-one patients (12%) suffered a recurrence during the follow-up period. Age (HR 1.04, 95% CI 1.01 to 1.06, p=0.014), and level of C reactive protein (HR 1.01, 95% CI 1.00 to 1.02, p=0.018) on admission were significantly associated with recurrence in the univariate analyses. Male gender (HR 0.61, 95% CI 0.35 to 1.05, p=0.076), body mass index (HR 0.94, 95% CI 0.87 to 1.01, p=0.093), hypertension (HR 0.59, 95% CI 0.33 to 1.06, p=0.079), diastolic blood pressure (HR 0.99, 95% CI 0.97 to 1.00, p=0.087) and haematocrit (HR 0.95, 95% CI 0.91 to 1.00, p=0.052) were marginally significant in the univariate Cox analyses. Multivariate Cox proportional hazards analysis showed that age (HR 1.03, 95% CI 1.00 to 1.06, p=0.031, per 1-year increase), and C reactive protein (HR 1.01, 95% CI 1.00 to 1.02, p=0.022, per 1 mg/L increase) were independent predictors of a recurrence in the first year after cardioembolic stroke. CONCLUSIONS: In patients with cardioembolic ischaemic stroke, age and C reactive protein are independent risk factors for recurrence in the first year after onset. PMID- 24231461 TI - Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study. AB - OBJECTIVES: We examined the association of plasminogen activator inhibitor-1 (PAI 1) levels with colorectal cancer, breast cancer, acute coronary syndrome (ACS) and ischaemic stroke. DESIGN: Nested case-cohort study. SETTING: The European Prospective Investigation into Cancer and Nutrition-Italy cohort. PARTICIPANTS: A centre-stratified random sample of 850 participants (286 men, 564 women) was selected as subcohort and compared with 303 colorectal cancers, 617 breast cancers, 688 ACS and 158 ischaemic strokes, in a mean follow-up of 9.11 years. MAIN OUTCOMES AND MEASURES: Primary incident cases of colon cancer, breast cancer, ACS and ischaemic stroke. PAI-1 levels were measured in citrated plasma by ELISA. HR and 95% CI, adjusted by relevant confounders and stratified by centre, were estimated by a Cox regression model using Prentice method. RESULTS: Individuals in the highest compared with the lowest quartile of PAI-1 had significantly increased risk of colorectal cancer (RR=2.28; 95% CI 1.46 to 3.55; P for trend<0.0012), breast cancer (HR=1.70; 95% CI 1.21 to 2.39; p<0.0055), ACS (HR=2.57; 95% CI 1.75 to 3.77; p<0.001) and ischaemic stroke (HR=2.27; 95% CI 1.28 to 4.03; p<0.0017), after adjustment for sex and age. Additional adjustment for disease-specific confounders, insulin or other metabolic variables did not modify the associations. Risk of colon cancer was stronger for men and for whole and distal colon localisation. Risk for breast cancer was stronger in postmenopausal women. CONCLUSIONS: Our data provide the first evidence that elevated levels of PAI-1 are potential risk factors for colorectal and breast cancer and a common pathway for cancer and cardiovascular disease. PMID- 24231462 TI - The association of cycling with all-cause, cardiovascular and cancer mortality: findings from the population-based EPIC-Norfolk cohort. AB - OBJECTIVES: To investigate associations between modest levels of total and domain specific (commuting, other utility, recreational) cycling and mortality from all causes, cardiovascular disease and cancer. DESIGN: Population-based cohort study (European Prospective Investigation into Cancer and Nutrition study-Norfolk). SETTING: Participants were recruited from general practices in the east of England and attended health examinations between 1993 and 1997 and again between 1998 and 2000. At the first health assessment, participants reported their average weekly duration of cycling for all purposes using a simple measure of physical activity. At the second health assessment, participants reported a more detailed breakdown of their weekly cycling behaviour using the EPAQ2 physical activity questionnaire. PARTICIPANTS: Adults aged 40-79 years at the first health assessment. PRIMARY OUTCOME MEASURE: All participants were followed for mortality (all-cause, cardiovascular and cancer) until March 2011. RESULTS: There were 22 450 participants with complete data at the first health assessment, of whom 4398 died during follow-up; and 13 346 participants with complete data at the second health assessment, of whom 1670 died during follow-up. Preliminary analyses using exposure data from the first health assessment showed that cycling for at least 60 min/week in total was associated with a 9% reduced risk of all-cause mortality (adjusted HR 0.91, 95% CI 0.84 to 0.99). Using the more precise measures of cycling available from the second health assessment, all types of cycling were associated with greater total moderate-to-vigorous physical activity; however, there was little evidence of an association between overall or domain-specific cycling and mortality. CONCLUSIONS: Cycling, in particular for utility purposes, was associated with greater moderate-to-vigorous and total physical activity. While this study provides tentative evidence that modest levels of cycling may reduce the risk of mortality, further research is required to confirm how much cycling is sufficient to induce health benefits. PMID- 24231463 TI - Response to: tea and coffee scalds in children: a British epidemic requiring a solution. PMID- 24231464 TI - Indocyanine green dye angiography accurately predicts survival in the zone of ischemia in a burn comb model. AB - INTRODUCTION: Surgical evaluation of burn depth is performed via clinical observation, with only moderate reliability. While perfusion analysis has been proposed to enhance accuracy, no perfusion study has attempted to predict burn extension into the area of ischemia surrounding the original insult. We examined whether laser Doppler imaging (LDI) and indocyanine green (ICG) angiography predicted survival in the zone of ischemia in a porcine hot comb burn model. METHODOLOGY: Six full-thickness wounds were created on 5 female Yorkshire swine using a validated porcine hot comb burn model. 4 full-thickness burns were created separated by 3 unburned interspaces that represent the zone of ischemia. The interspaces between each comb burn were monitored using LDI and ICG Angiography at 1, 4, 24, and 48 h after burn. Interspace survival was assessed via gross observation and blinded histological readings 7 days after injury. RESULTS: ICG Angiographic assessments of burn perfusion were significantly different in viable vs. non-viable interspace perfusion at 1 h, 4 h, and 48 h. Temporal plotting of a trend-line derived from quantitative perfusion measurements rendered two distinct graphs, allowing for the derivation of a predictive algorithm to separate viable and non-viable interspaces. LDI revealed no such prognostic trend. CONCLUSION: Results from a validated porcine burn comb model suggest that ICG angiography has significant potential in the prediction of burn progression early after burn. However, the full potential of this technology cannot be determined until completion of clinical trials. PMID- 24231465 TI - Disease models of chronic inflammatory airway disease: applications and requirements for clinical trials. AB - PURPOSE OF REVIEW: This review will discuss methodologies and applicability of key inflammatory models of respiratory disease in proof of concept or proof of efficacy clinical studies. In close relationship with these models, induced sputum and inflammatory cell counts will be addressed for phenotype-directed drug development. Additionally, important regulatory aspects regarding noninvestigational medicinal products used in bronchial challenges or clinical inflammatory models of respiratory disease will be highlighted. RECENT FINDINGS: The recognition of an ever increasing number of phenotypes and endotypes within conditions such as asthma and chronic obstructive pulmonary disease urges phenotyping of study populations already in early clinical phases of drug development. Apart from the choice of a relevant disease model, recent studies show that especially targeted therapies need to be tested in well defined disease subsets for adequate efficacy assessment. Noninvasive biomarkers, especially sputum inflammatory cell counts, aid phenotyping and are useful outcome measures for novel, targeted therapies. SUMMARY: Disease phenotyping becomes increasingly important for efficient and cost-effective drug development and subsequent disease management. Inflammatory models of respiratory disease combined with sputum biomarkers are important tools in this approach. PMID- 24231466 TI - Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni). AB - Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis. PMID- 24231467 TI - Blood oxygen- and carbon dioxide-carrying properties in captive penguins: effects of moulting and inter-specific comparison. AB - Venous blood gas-carrying properties were compared in the three captive species of penguins (king, gentoo and rockhopper) at Oceanopolis (France). Captivity permitted to control environmental influences. Given their different ecology and diving behaviour in the wild, it was wondered whether milder conditions and dive privation have repercussions on parameters determining oxygen storage and acid base status of these birds. In addition, this work provided the opportunity to study the effects of moulting in king penguins. This annual event that imposes deep metabolic adjustments is liable to affect blood gas levels. Because of the regular food supply and probably also of the blood sampling conditions, the blood pH of captive penguins was low. This effect was increased in moulting penguins and supposedly due to both the decreased energetic metabolism and the production of uric acid resulting from new feather synthesis. The decrease in the anion gap also revealed the use of plasmatic albumin for this synthesis. The elevated venous PO2 in all birds is not likely due to stress caused by sampling conditions. The other data, in accordance with those in the literature, show neither major influence of captivity nor fundamental interspecific differences, despite potential diving aptitude. PMID- 24231468 TI - Distinct patterns of HSP30 and HSP70 degradation in Xenopus laevis A6 cells recovering from thermal stress. AB - Heat shock proteins (HSPs) are molecular chaperones that assist in protein synthesis, folding and degradation and prevent stress-induced protein aggregation. In this study, we examined the pattern of accumulation of HSP30 and HSP70 in Xenopus laevis A6 kidney epithelial cells recovering from heat shock. Immunoblot analysis revealed the presence of elevated levels of HSP30 after 72h of recovery. However, the relative levels of HSP70 declined to near control levels after 24h. The relative levels of both hsp30 and hsp70 mRNA were reduced to low levels after 24h of recovery from heat shock. Pretreatment of cells with cycloheximide, a translational inhibitor, produced a rapid decline in HSP70 but not HSP30. The cycloheximide-associated decline of HSP70 was blocked by the proteasomal inhibitor, MG132, but had little effect on the relative level of HSP30. Also, treatment of cells with the phosphorylation inhibitor, SB203580, in addition to cycloheximide treatment enhanced the stability of HSP30 compared to cycloheximide alone. Immunocytochemical studies detected the presence of HSP30 accumulation in a granular pattern in the cytoplasm of recovering cells and its association with aggresome-like structures, which was enhanced in the presence of SB203580. This study has shown that the relative levels of heat shock-induced HSP30 persist during recovery in contrast to HSP70. While HSP70 is degraded by the ubiquitin-proteasome system, it is likely that the presence of HSP30 multimeric complexes that are known to associate with unfolded protein as well as its association with aggresome-like structures may delay its degradation. PMID- 24231469 TI - Rapid and sustained GluA1 S845 phosphorylation in synaptic and extrasynaptic locations in the rat forebrain following amphetamine administration. AB - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is a major ionotropic glutamate receptor subtype in the mammalian brain. Like other glutamate receptors, the AMPA receptor is regulated by phosphorylation. By phosphorylating specific serine resides in AMPA receptor subunits (GluA1 and GluA2), various protein kinases regulate subcellular/subsynaptic expression and function of the receptor. In this study, we conducted a time course study to evaluate the temporal property of responses of phosphorylation at those sites to dopamine stimulation with the psychostimulant amphetamine in the adult rat striatum and medial prefrontal cortex (mPFC) in vivo. We focused on biochemically enriched AMPA receptors from synaptic and extrasynaptic compartments. We found that acute injection of amphetamine induced a rapid and relatively sustained increase in GluA1 S845 phosphorylation at both synaptic and extrasynaptic sites in the striatum. Similar results were observed in the mPFC. In contrast to S845, amphetamine did not induce a significant change in GluA1 S831 phosphorylation in synaptic and extrasynaptic pools in the striatum and mPFC. GluA2 S880 phosphorylation in synaptic and extrasynaptic fractions in the two brain regions also remained stable in response to amphetamine. These results support S845 to be a principal site on AMPA receptors sensitive to acute stimulant exposure. Its phosphorylation levels are rapidly upregulated by amphetamine in the two defined subsynaptic microdomains (synaptic versus extrasynaptic locations) in striatal and cortical neurons. PMID- 24231470 TI - The protective effect of eicosapentaenoic acid-enriched phospholipids from sea cucumber Cucumaria frondosa on oxidative stress in PC12 cells and SAMP8 mice. AB - Alzheimer's disease (AD) is a common neurodegenerative disorders, in which oxidative stress plays an important role. The present study investigated the effect of eicosapentaenoic acid-enriched phospholipids (EPA-enriched PL) from the sea cucumber Cucumaria frondosa on oxidative injury in PC12 cells induced by hydrogen peroxide (H2O2) and tert-butylhydroperoxide (t-BHP). We also studied the effect of EPA-enriched PL on learning and memory functions in senescence accelerated prone mouse strain 8 (SAMP8) in vivo. Pretreatment with EPA-enriched PL resulted in an enhancement of survival in a dose-dependent manner in H2O2 or t BHP damaged PC12 cells. EPA-enriched PL pretreatment could also reduce the leakage of lactate dehydrogenase (LDH), and increase the intracellular total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity compared with the H2O2 or t-BHP group. The down-regulated Bcl-2 mRNA level and up regulated Bax, Caspase-9, and Caspase-3 mRNA expression induced by H2O2 or t-BHP could be restored by EPA-enriched PL pretreatment. These results demonstrated that EPA-enriched PL exhibited its neuroprotective effects by virtue of its antioxidant activity, which might be achieved by inhibiting the mitochondria dependent apoptotic pathway. The neuroprotective effect of EPA-enriched PL was also verified in vivo test: the EPA-enriched PL administration prevented the development of learning and memory impairments in SAMP8 mice. Our results indicated that EPA-enriched PL could offer an efficient and novel strategy to explore novel drugs or functional food for neuronprotection and cognitive improvement. PMID- 24231471 TI - Good riddance to dopamine: roles for the dopamine transporter in synaptic function and dopamine-associated brain disorders. AB - The neurotransmitter dopamine (DA) plays a critical role in CNS circuits that provide for attention, executive function, reward responses, motivation and movement. DA is inactivated by the cocaine- and amphetamine-sensitive DA transporter (DAT), a protein that also provides a pathway for non-vesicular DA release. After a brief review of DAT function and psychostimulant actions, we consider the importance DAT in relation to the distinct firing patterns of DA neurons that permit awareness of novelty and reward. Finally, we review recent efforts to gather direct support for DAT-linked disorders, with a specific focus on DAT mutations recently identified in subjects with ADHD. PMID- 24231472 TI - Novel troponin-like biomarkers of acute kidney injury. AB - Acute kidney injury (AKI) is a common and serious condition in both the inpatient and outpatient settings, and its diagnosis depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has limited our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has realized a number of potential biomarkers. For example, neutrophil gelatinase-associated lipocalin is emerging as an excellent stand alone troponin-like biomarker in the plasma and urine for predicting and monitoring clinical trials and in the prognosis of AKI. In recent years, a number of new biomarkers of AKI with more favorable test characteristics than creatinine have been identified and studied in a variety of experimental and clinical settings. This review will consider the most well-established biomarkers of AKI. PMID- 24231473 TI - The impact of CYP3A5 and MDR1 polymorphisms on tacrolimus dosage requirements and trough concentrations in pediatric renal transplant recipients. AB - Previous international studies demonstrated significant heterogeneity in the tacrolimus (TAC) dose required to attain target blood concentrations, attributed to both genetic and ethnic factors. While the majority of previous reports on adult recipients of renal, heart and liver transplants have shown a significant effect of CYP3A5FNx013 single nucleotide polymorphisms (SNPs) on TAC pharmacokinetics (PKs), the impact of multidrug resistance protein 1 (MDR1) and SNPs remains controversial. Yet, similar data of TAC in pediatric populations, in whom the intra- and inter-subject variations are likely to be even greater, is currently limited. We aimed to examine the influence of various CYP3A5 and MDR1 genotypes on TAC dose requirements and PKs in the Jordanian pediatric renal transplant population. Thirty-eight patients were genotyped for CYP3A5FNx011 and FNx013 and MDR1 C3435T. Dose-adjusted trough concentrations (C 0 /D) and daily doses (D) were compared among different CYP3A5 and MDR1 genotypes in the early and maintenance phases post-transplant. Surprisingly, there were no significant differences in D, C 0 or C 0 /D among the genotypes of CYP3A5 or MDR1 polymorphisms in either the early or the maintenance phase after transplantation, whereas after combining the C 0 /D levels of MDR1 C allele expressers, noticeably lower TAC levels were observed as compared with the TT genotype. However, the difference became not significant beyond 3 months. Based on a pharmacogenetic evaluation, the independent impact of CYP3A5 SNPs on TAC PKs was not evident, demonstrating the need for further large-scale studies. PMID- 24231474 TI - Mismatched related hematopoietic stem cell transplantation in primary immunodeficiency. AB - Hematopoietic stem cell transplantation (HSCT) is the definitive therapy for a variety of primary immunodeficiency syndromes (PIDs). However, no more than 30% of the patients will have a human leukocyte antigen (HLA)-identical sibling. We retrospectively analyzed our results of ten patients with PID; severe combined immunodeficiency (SCID) (n = 7), hyper IgM (HIgM) (n = 1) and combined immunodeficiency (CID) (n = 2), who lacked a fully matched donor and underwent mismatched related HSCT during the period from 2008 to 2010. The median age at the time of transplantation ranged between 3 and 84 months (median 6.5 months). Peripheral blood stem cells (PBSC) were used in all HSCTs. The mean value of the peripheral CD34+ cells infused was 9.19 * 10 (6) /kg recipient weight. Patients received different conditioning protocols. All patients received anti graft versus host disease (GVHD) prophylaxis and all were engrafted. Mixed chimerism (5 55%) was noticed. GVHD was observed in 50% of the patients. Post-transplant follow-up ranged from 3 weeks to 36 months (median 15 months). Five patients are still alive while one patient developed engraftment syndrome followed by graft slippage for which a second transplant with CD34+ stem cells 5.8 * 10 (6) /kg recipient's weight was infused. The others died from sepsis and transplant related complications. Immune reconstitution was noticed in four patients. In conclusion, HLA-haploidentical stem cell transplantation may be feasible, with appropriate GVHD prophylaxis, for patients with PID who lack a fully matched donor. PMID- 24231475 TI - Ultra-early onset post-transplantation lymphoproliferative disease. AB - Post-transplant lymphoproliferative disease (PTLD) can present as early as days to as late as several decades after transplantation. This study, however, tries to research PTLD characteristics including histopathological and clinical features, predictors and prognosis of the disease when occurring within the first month post-transplantation. We conducted a comprehensive search for the available data using the Pubmed and Google scholar search engines for reports indicating presentation time in PTLD patients. Data from 25 previously published studies were included in the analysis. Finally, we found 355 recipients of organs presenting with "ultra-early onset PTLD." Transplant recipients with ultra-early onset PTLD were significantly more likely to have kidney allografts (P = 0.032). Transplant recipients with ultra-early onset PTLD were comparable to their counterparts in the control group in their demographics, histopathological findings and survival. Patients with ultra-early onset PTLD were significantly more likely to receive induction therapy (100% vs. 49%, respectively; P = 0.013). Pancreas transplant recipients were at a significantly higher risk for development of ultra-early onset PTLD (20% vs. 1%, respectively; P <0.001). Our findings emphasize the importance of immunosuppression potency as well as the type of allograft transplanted on the incidence of PTLD in the early stages after transplantation. However, we found no histopathological or outcome disparities for patients with ultra-early PTLD compared with controls. Further prospective studies with more comparable approaches to the patients are needed to confirm our findings. PMID- 24231476 TI - The role of erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency in the pathogenesis of anemia in patients on hemodialysis. AB - Anemia is a common feature among patients with chronic renal failure (CRF). Low activity of the erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD), which plays a major role in protecting red blood cells against oxidative agents, has been described as one of the contributing factors to anemia in patients with CRF treated with hemodialysis (HD). In this study, blood samples were randomly collected from 65 patients on HD and investigated for G6PD deficiency using the methemoglobin reduction test. The hemoglobin (Hb) concentration, packed cell volume (PCV), red blood cells (RBCs) count and reticulocyte count were determined in all the samples. Our results showed that 39 of 65 patients (60%) on HD had low G6PD activity and 26 (40%) patients had normal activity; 59% of the patients with low G6PD activity were males. The mean Hb, PCV and RBCs counts were lower in patients with low G6PD activity than in those with normal G6PD activity, but the difference was not statistically significant. Likewise, no statistically significant difference was found in the reticulocyte count in patients with low G6PD activity and in those with normal G6PD activity. The low G6PD activity that was found in a large proportion of patients on HD seems to be the result of enzyme inhibition rather than deficiency. No statistically significant difference was found in anemia parameters between patients with and without G6PD deficiency. PMID- 24231477 TI - The relationship between the antioxidant system, oxidative stress and dialysis related amyloidosis in hemodialysis patients. AB - End-stage renal disease (ESRD) is associated with several complications that are partly due to excess amounts of reactive oxygen species and/or decreased antioxidant activity. Dialysis-related amyloidosis (DRA) has also been linked to increased oxidative stress. The aim of this study was to investigate the relationships between the antioxidant system, including superoxide dismutase (SOD), malonyldialdehyde (MDA), various biochemical parameters and shoulder amyloidosis, in hemodialysis patients. We studied 107 non-diabetic chronic dialysis patients. The SOD levels correlated with right and left biceps tendon thickness (r = -0.219, P = 0.048 and r = -0.236, P = 0.031, respectively), MDA (r = -0.429, P = 0.000) and albumin levels (r = -0.319, P = 0.001). MDA levels correlated with right and left biceps thickness (r = 0.291, P = 0.006 and r = 0.337, P = 0.001, respectively) and beta2 microglobulin levels (r = 0.455, P = 0.000). We also identified the statistically significant relationships between MDA levels and supraspinatus tendon thickening (greater than 7 mm) and right and left biceps tendon thickness (P = 0.022, P = 0.040 and P = 0.005, respectively). Our data suggest the complex relationship between antioxidants and oxidative stress and further support the roles of oxidative stress and antioxidants in DRA. PMID- 24231478 TI - Predictors of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism. AB - We sought to identify predictors of development of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism. The patients were divided into two groups according to their serum calcium (Ca) levels within 24 hours of undergoing para-thyroidectomy: the hypocalcemia group (22 patients) with post-operative serum Ca levels of 2 mmol/L or less, and the normocalcemia group (48 patients), with post-operative serum Ca levels higher than 2 mmol/L. By using multivariate stepwise logistic regression analysis, high pre-operative serum Ca level had the strongest predictive value of development of early hypocalcemia with an adjusted odds ratio (aOR) of 3.01, followed by hypo albuminemia (aOR = 2.72), younger age (aOR = 2.56), and high pre-operative alkaline phosphatase (ALP) levels (aOR = 2.28). We conclude that among patients with secondary hyperparathyroidism, age, levels of pre-operative serum Ca, ALP and albumin correlate positively with the development of early post-operative hypocalcemia. Patients with one of these factors should be monitored more closely in the early post-parathyroidectomy period. PMID- 24231479 TI - Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis. AB - Peritoneal dialysis offers several advantages such as better clearance of intermediate/large molecules and better preservation of renal residual function when compared with hemodialysis. However, dialysis adequacy is one of the subjects of concern of this modality. There are some drugs that are capable of influencing solute transport in the peritoneum, such as acetyle co-enzyme inhibitors (ACE-I) medications and calcium channel blockers. Captopril and Verapamil are often mentioned, but their use has shown varying conclusions and initial studies were performed with the intra-peritoneal administration of these drugs and there are only a few studies on the effect of the oral administration of these drugs. This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD) patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET) test). However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti hypertensive medication of choice in CAPD patients, which can also result in better dialysis adequacy. However, further studies with larger sample sizes are needed in the future. PMID- 24231480 TI - The renal recovery of critically ill patients with acute renal failure requiring dialysis. AB - The incidence of acute renal failure (ARF) is increasing and will nearly double over the next decades as the population ages. As a result of ARF, patients will have longer hospital stays and may require dialysis as outpatients. The aim of this cohort study was to examine the renal recovery after the hospital discharge of surviving critically ill patients who developed ARF that required dialysis. During the 3-year study, there were 2574 patients admitted to the intensive care unit; 308 (12%) patients developed ARF and needed dialysis, 86 (28%) patients survived to hospital discharge and 40 (47%) patients continued to require dialysis after discharge. There were no differences of age or gender in the dialysis group from the non-dialysis group. In addition, there were no differences between the groups in terms of the severity of illness, use of mechanical ventilation, history of hypertension, creatinine levels, urine output or use of inotropes. It was not uncommon for surviving patients with ARF that required dialysis to be dialysis dependent upon hospital discharge, which represents an important cause of chronic kidney disease. PMID- 24231481 TI - Occurrence of microalbuminuria among children and adolescents with insulin dependent diabetes mellitus. AB - Microalbuminuria precedes the onset of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) pediatric patients. Its prevention is among the most important challenges in managing IDDM. We attempted to determine the occurrence of microalbuminuria among IDDM Saudi children and adolescents and its associated risk factors. This is a retrospective cross-sectional study conducted on 409 IDDM children and adolescents attending the pediatric clinic at King Abdul-Aziz University Hospital from 2006 to 2010. Their ages ranged from 1 to 18 years and the mean +/- standard deviation (mean +/- SD) was 12.3 +/- 4.1 years. Twenty-four hour urinary albumin excretion (on two separate occasions or more, 3 - 6 months apart each), HbA1c, duration of IDDM, Tanner staging and body mass index (BMI) were reviewed. Prevalence of microalbuminuria in our cohort was 11.3%. IDDM duration was >=2 years in 55.8% of our patients; of them, 15.6% had microalbuminuria while 45.2% had IDDM duration <2 years (6% had microalbuminuria) (P <0.01). The prevalence of microalbuminuria was higher among the post-pubertal subjects (50%) than that among the pre-pubertal (8.7%) and pubertal (41.5%) subjects. Furthermore, microalbuminuria was present in 16.7% of those with elevated blood pressure, but only in 8.5% among those with normal blood pressure (P <0.05). The enrolled overweight and obese subjects showed a higher prevalence of microalbuminuria (14%) when compared with that among those with a normal BMI (6.6%) (P <0.05). In our cohort, duration of IDDM, pubertal status, hypertension and BMI affected the prevalence of microalbuminuria. Annual screening for microalbuminuria in IDDM children and adolescents is imperative. PMID- 24231482 TI - Risk factors of chronic kidney disease influencing cardiac calcification. AB - We sought to determine the influence of risk factors of chronic kidney disease (CKD) on cardiac calcification. We studied the correlation between coronary artery calcium score (CACS) and the type and duration of dialysis as well as the presence of diabetes mellitus and hypertension. The relation between calcium score and mortality was also analyzed. Patients with CKD attending the outpatient department or admitted in our hospital were included. They were subjected to high resolution computerized tomography of the thorax to determine their CACS. Serum levels of intact parathyroid hormone (iPTH), highly sensitive C-reactive protein (hCRP), homocysteine, calcium, phosphorus, and calcium * phosphorus product were measured. Out of the 50 patients studied, 39 were hypertensive (78%), 32 were diabetic (64.4%), 20 were on hemodialysis, and 13 were on continuous ambulatory peritoneal dialysis. The mean CACS was 388.6. Twenty-nine patients had high iPTH levels and 92.9% of them had calcium score >400 (P = 0.013). Twenty-eight patients had high hCRP and 85.7% of these patients had calcium score >400 (P = 0.048). Patients on dialysis for more than two years had higher calcium score >400 (P = 0.035). 43% of diabetics had calcium score >400 (P = 0.008). All the six patients who died had calcium score >400 (P = 0). There was statistically no significant association noted between hypertension, high calcium x phosphorus product, and high homocysteine levels, and high calcium score. Our study suggests that higher values of iPTH, hCRP, and longer duration on dialysis are associated with accelerated cardiac calcification. Calcification scores >400 are associated with increased mortality. PMID- 24231483 TI - Pre-emptive treatment of hepatitis B infection by lamivudine in two Tunisian renal transplant recipients. AB - Infection with hepatitis B virus has a major implication for transplant recipients due to the risk of reactivation under immunosuppression, progression to chronic liver disease, development of liver cirrhosis and hepatocellular carcinoma. We report two cases of renal transplantation patients who were hepatitis B surface antigen positive before transplantation and were treated by Lamivudine. PMID- 24231484 TI - Kaposi's sarcoma with HHV8 infection and ANCA-associated vasculitis in a hemodialysis patient. AB - The association between Kaposi's sarcoma (KS) and human herpes virus eight (HHV 8) infection is rarely reported in hemodialysis (HD) patients. We report here the rare association of KS, HHV-8 and hepatitis C virus (HCV) infection as well as syphilis in a HD patient. We report the case of a 72-year-old woman who presented with microscopic polyangiitis with alveolar hemorrhage and pauci-immune necrosing and crescentic glomerulonephritis as well as renal failure requiring HD. Biological tests showed positive HCV and syphilis tests. The patient was treated by HD and intravenous pulse, followed by oral corticosteroids and six cyclophosphamide monthly pulses with remission of the alveolar hemorrhage, but without renal functional recovery as the patient remained HD dependent. Five months after the first treatment administration, she developed extensive purpuric lesions on her lower limbs, abdomen face and neck. A skin biopsy showed KS. The HHV-8 test was positive, with positive polymerase chain reaction-HHV8 in the serum and skin. After immunosuppression withdrawal, the KS skin lesions regressed rapidly without relapse after 12 months of follow-up, but alveolar hemorrhage relapsed after 16 months of follow-up. Our case showed that the immunosuppressed state related to multiple factors such as aging, vasculitis, HHV-8, HCV, syphilis, immunosuppressive therapy and HD may all have contributed to the development of KS in our patient. PMID- 24231485 TI - Encapsulating peritoneal sclerosis. AB - Encapsulating peritoneal sclerosis (EPS) is a rare but potentially lethal complication of peritoneal dialysis (PD). Peritoneal tuberculosis is considered an etiologic factor. We report a case of EPS in a 40-year-old man who was switched to hemodialysis because of peritoneal tuberculosis after 2 years of PD. Because of the persistence of gastrointestinal symptoms and cachexia, laparoscopic exploration was performed, which revealed an important thickening of the peritoneal membrane sheathing the intestinal loops. Accordingly, a diagnosis of EPS was made. Anti-tuberculosis treatment associated with a low dose of corticosteroids stabilized the disease. PMID- 24231486 TI - Non-hemorrhagic dengue fever with rhabdomyolysis. AB - Acute kidney injury occurs in 33-50% of patients with rhabdomyolysis and infections remain one of the major contributing factors. The incidence of rhabdomyolysis in non-hemorrhagic dengue virus infection is quite low and may go unnoticed, especially if the presentation is not florid. We report a case of a young male patient, sero-positive for dengue, with no hemorrhagic manifestations or hypotension, who developed rhabdomyolysis complicated by renal failure. The patient eventually needed dialysis support and later recovered fully. Clinicians need to be aware of the occurrence of rhabdomyolysis even in patients without the hemorrhagic manifestations of dengue viral infection and should employ early preventive strategies in such cases. PMID- 24231487 TI - Does NPHS1 polymorphism modulate P118l mutation in NPHS2? AB - Nephrotic syndrome (NS) in the first year of life is uncommon and makes up a heterogeneous group of disorders. Subsequent studies have further defined the phenotype associated with mutations in the NPHS2 gene, revealing that patients usually develop NS from birth to 6 years of age. We report a child aged 4 months with steroid-resistant NS who had polymorphism of NPHS1 (E117K) and mutation of NPHS2 (P118L). Our patient was carrying a polymorphic NPHS1 mutation, while phenotypically she had a poor prognostic NPHS2 mutation. However, it must be questioned whether this polymorphic change (E117K) alters the signaling pathways of the podocytes and leads to P118L mutation, thus making it behave differently. Perhaps, this would be called a genetic modifier in future. PMID- 24231488 TI - Renal failure in Hay-Wells syndrome. AB - Ectodermal dysplasia (ED) is a group of disorders involving developmental defects of the ectodermal structures, with abnormalities in the skin, hair, nails and sweat glands. Ankyloblepharon - ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is characterized by eyelid fusion, ED and cleft lip/palate. We report a 15-year-old Omani boy with AEC syndrome who presented with end-stage renal disease (ESRD) requiring renal replacement therapy. Genitourinary anomalies including hypospadiasis, posterior urethral stricture and bilateral vesicoureteric reflux were noted. These led to secondary focal segmental glomerulosclerosis and ESRD. Screening for genitourinary anomalies and renal function tests must be performed in all patients with ED to facilitate early detection of renal disease and appropriate management. PMID- 24231489 TI - Refeeding syndrome in a patient with advanced kidney failure due to nephronophthisis. AB - Refeeding syndrome (RS) is a serious and potentially fatal disorder. It is caused by a shift of fluids, sodium, potassium, magnesium and phosphorus as well changes in the metabolism of glucose, protein, fat and vitamins following the refeeding of malnourished patients, whether enterally or parenterally. RS has rarely been reported in patients with advanced kidney disease probably due to the pre existing hyperphosphatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present a patient with nephronophthisis type 1 deletion syndrome in whom her main previous nutrition was limited to simply rehydration to avoid renal replacement therapy. On presentation, she was cachectic and dehydrated with advanced kidney failure. She was treated with medical nephrectomy using non-steroidal anti-inflammatory drugs and then placed on maintenance hemodialysis. Percutaneous endoscopic gastrostomy was used for her initial feeding. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, the changes in the gut, pancreas and liver as well as her hyperlipidemia were a clear obstacle. Fortunately, the ileus and pancreatitis she developed on refeeding improved dramatically with a decrease of the feeding dose to half; however, the liver abnormalities and hyperlipidemia were severe and slow to recover. These improved after addition of ursodeoxycholic acid and permitted successful increase of the dose of feeding subsequently. PMID- 24231490 TI - Pauci-immune crescentic glomerulonephritis in the Down's syndrome. AB - Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression. PMID- 24231491 TI - Successful elimination of hemodialysis-related bacteremia and vascular access infection. AB - Hemodialysis (HD) related bacteremia and dialysis induced infection constitute major risk factors for mortality and morbidity among patients with end stage renal disease. In this retrospective study, we attempted to assess the impact of the infection control protocol introduced in our center on the prevalence of HD related bacteremia and vascular access infection. All the HD sessions performed over 8 years, from January 2004 till the end of December 2011, were included in this study. Over 108 months of the study period, 6161 HD sessions were performed on 118 patients. Demographic data of all the study patients were collected. The type of vascular access as well as the presence of diabetes and hypertension were recorded. During the study period, 15 episodes of dialysis related bacteremia were noted in nine patients. Three of them required hospitalization for administration of parenteral antibiotics. Blood cultures in 93% of the infection episodes (14/15) grew Sphingomonas paucilomobilis. One patient had methicillin resistant Staphylococcus aureus grown on blood culture. The prevalence of HD related bacteremia and vascular access infection in our unit were lower than international published data. The infection control protocol used seems to have been successful in reducing HD related bacteremia and eliminating vascular access infection. PMID- 24231492 TI - Nocturnal enuresis among primary school children. AB - To determine the prevalence and personal and family risk factors for nocturnal enuresis (NE) among primary school children in Al-Mukalla City, Yemen, we conducted a cross-sectional survey using a self-administered, three-part structured questionnaire involving 832 school children aged 6 - 15 years between 2007 and 2008. We assessed participants' socio-demographic factors, family characteristics and factors related to the presence of NE. The mean age of the children was 11.5 (+/-2.7) years. The overall prevalence of NE was 28.6%, with a predominance of girls, and the prevalence decreased with increasing age (P <0.001). Factors likely to be associated with NE were pattern of sleeping (P <0.001), stressful social and psychological events (P <0.01), positive family history of enuresis (P <0.001), large family size (P >0.002) and a higher number of siblings (P = 0.01). Our findings reveal a high prevalence of NE among children in Al-Mukalla City, Yemen, with a higher prevalence in girls than in boys compared with the other studies. Sleep pattern, stressful life events, family history of NE, large family size and more children in the household may act as a risk factor for NE. PMID- 24231493 TI - Risk factors and management of diabetic nephropathy. AB - To determine the risk factors for nephropathy in diabetic patients and to study the management of diabetic nephropathy (DN), we conducted a hospital-based prospective study in the Internal Medicine department of our hospital on 60 patients with DN and 60 diabetic patients without DN. An odds ratio (OR) disclosed the following risk factors: Hypertension (OR = 2.06), family history of diabetes (OR = 1.23), family history of DN (OR = 2.86), uncontrolled hyperglycemia (OR = 11.80), obesity (OR = 1.07), duration of diabetes between 11 and 20 years (OR = 4.69), smoking (OR = 2.79), alcohol consumption (OR = 3.75), other complications (OR = 2.03), lack of physical activity (OR = 1.51) and anemia (OR = 2.29). According to these risk factors, we suggest that improving patient's knowledge on diabetes and its treatment, life style modifications and aggressive management of the disease may delay the progression of disease to advanced stages. PMID- 24231494 TI - Cytomegalovirus infection following renal transplantation: an analysis of 21 cases in an endemic area. PMID- 24231495 TI - Dialysis access technology, the next generation. PMID- 24231496 TI - Ultrasound findings in urinary schistosomiasis infection in school children in Gezira State, Central Sudan. PMID- 24231497 TI - Acute renal failure associated with malaria in children. PMID- 24231498 TI - Symptoms of anxiety among patients with chronic kidney disease in Sri Lanka. PMID- 24231499 TI - Major flooding in central Thailand: the problem related to availability of dialysis fluid. PMID- 24231500 TI - Fathoming uric acid nephropathy. PMID- 24231501 TI - Celiac disease a rare cause of nephrogenic ascites. PMID- 24231502 TI - Pattern of glomerular disease in the Saudi population: a single-center, five-year retrospective study. AB - Glomerular diseases continue to be the leading cause of end-stage renal disease (ESRD) globally. Hence, it is important to recognize the pattern of glomerular diseases in different geographical areas in order to understand the patho biology, incidence and progression of the disorder. Published studies from different centers in Saudi Arabia have reported contradicting results. In this retrospective study, we report our experience at the Armed Forces Hospital, Riyadh, Saudi Arabia. A total of 348 native renal biopsies performed at our center on patients with proteinuria >1 g, hematuria and/or renal impairment during a period of 5 years (between January 2005 and December 2009) were studied by a histopathologist using light microscopy, immunofluorescence and electron microscopy, and were categorized. Results showed that primary glomerular disease accounted for 55.1% of all renal biopsies. The most common histological lesion was focal and segmental glomerulosclerosis (FSGS) (27.6%), followed by minimal change disease (MCD) (17.7%) and membrano-proliferative glomerulonephritis (MPGN) (13.0%). Secondary glomerular disease accounted for 37.9% of the glomerular diseases, with lupus nephritis (LN) being the most common lesion (54.5%), followed by hypertensive nephrosclerosis (22%), post-infectious glomerulonephritis (7.5%), diabetic nephropathy (DN) (6.8%) and vasculitides (4.5%). Four percent of all biopsies turned out to be ESRD while biopsy was inadequate in 2.8% of the cases. In conclusion, our study showed that FSGS was the most common primary GN encountered, while LN was the most common secondary GN. We encountered 14 cases of crescentic glomerulonephritis. Also, the prevalence of MPGN, MCD, IgA nephropathy and membranous GN was many folds higher in males when compared with the Western data. We believe that it is mandatory to maintain a Saudi Arabian Renal Biopsy Registry to understand better the pattern of glomerular disease in the Saudi population and to follow any change in trend. PMID- 24231503 TI - Immunological aspects of biopsy-proven lupus nephritis in Bahraini patients with systemic lupus erythematosus. AB - Lupus nephritis (LN) is a frequent and potentially serious complication of systemic lupus erythematosus (SLE) that may influence morbidity and mortality. Immunological investigations are aiding tools to the kidney biopsy findings in early diagnosis, in addition to monitoring the effect of therapy. The aim of the present study is to highlight the role of these investigations in a group of Bahraini patients and to determine whether there is any positive association between these findings and the outcome of LN. The current study is a retrospective case-control study of randomly selected 88 SLE patients, 44 with biopsy-proven LN and 44 without, acting as controls. All renal biopsies performed during the period from 1996 to 2012 were classified according to the World Health Organization classification. Immunological investigations analyzed are: Antinuclear antibodies (ANA), anti-ds DNA, anti-ENA, anti-cardiolipin antibodies (abs) and complement components C3, C4. Human leukocyte antigen (HLA) typing class II was performed on selected cases. All patients had positive ANA (100%). A significantly high frequency of anti-Smith abs among the non-LN group (43.18%) compared with the LN group (18.18%) was found (P <0.001). On the other hand, the anti-Ro/SSA abs in the non-LN group was also found at a statistically higher frequency (20.45%) compared with that in the LN group (4.54%) (P <0.01). Anti-ds DNA abs were found to be higher in the LN group (84.09%) compared with the non-LN group (70.45%), but the difference was not statistically significant (P = 0.082). There was a positive association of ANA positivity and low C3 and or C4 in the studied group. In our study, 88.2% of the HLA typed patients had HLADR2, DR3 or both. In conclusion, in our Arabic Bahraini SLE patients, the presence of anti Smith, anti-Ro/SSA and anti-RNP antibodies and the absence of anti-dsDNA antibodies are independent predictive markers for renal involvement. However, more prospective studies with a larger number of patients are essential to ascertain those findings. PMID- 24231504 TI - Intercity deceased donor renal transplantation: a single-center experience from a developing country. AB - In a developing country such as India, deceased donor renal transplantation (DDRTx) accounts for only about 1% of all renal transplants (RTx). Our institute initiated an intercity DDRTx in the year 2006, which significantly increased the number of RTx. We retrieved 74 kidneys from 37 deceased donors from various cities of Gujarat from January 2006 to December 2009. We transplanted the allografts in 66 recipients and a retrospective analysis of the donor profile and management and recipient outcome was performed. The mean age of the donors was 43.3 +/- 18.8 years. The causes of death included road traffic accident in 51.35% of the donors and cerebrovascular stroke in 48.65% of the donors; 83.78% of the donors required ionotropes for hemodynamic stability in addition to vigorous intravenous fluid replacement. The average urine output of the donors was 350 +/- 150 mL. The organs were perfused and stored in HTK solution. The mean cold ischemia time (CIT) was 9.12 +/- 5.25 h. The mean anastomosis time in the recipient was 30.8 +/- 8.7 min. 57.6% of the recipients established urine output on the operating table and 42.4% developed delayed graft function. At the end of 1 month after transplantation, the mean serum creatinine was comparable to the Ahmadabad city DDRTx, although the CIT was significantly longer in the intercity patients. Intercity organ harvesting is a viable option to increase the donor pool. Distance may not be an impediment, and good recipient outcome is possible in spite of prolonged CIT in case of proper harvesting and preservation. PMID- 24231505 TI - Kidney disease in the elderly: a Sri Lankan perspective. AB - Renal disease in the elderly in Sri Lanka is a largely neglected area in the literature with hardly any publications. We carried out a hospital-based survey of elderly patients (elderly is defined in this article as patients aged 65 years or above) with renal disease. This prospective study included all patients aged 65 years or above admitted to the University Medical Unit, National Hospital of Sri Lanka, over a period of 1 year with a primary renal-related illness as the reason for hospitalization. This hospital-based survey is the first of its kind to look into the nephrological disease profile of elderly patients in Sri Lanka. Based on our findings, we have made several pertinent recommendations regarding the care of the elderly with renal disease in Sri Lanka that may be relevant to other developing nations as well. PMID- 24231506 TI - Renal function, urinalysis abnormalities and correlates among HIV-infected Cameroonians naive to antiretroviral therapy. AB - As per guidelines and recommendations, screening for renal diseases should be performed at the time of diagnosis of human immuno-deficiency virus (HIV) infection; however, this remains largely unimplemented in many settings across Sub-Saharan Africa. We evaluated the renal function, urinalysis abnormalities and their correlates in HIV-infected individuals who were naive to highly active antiretroviral therapy (HAART). This was a cross-sectional study of 2 months' duration involving 104 HIV-infected outpatients naive to HAART (71 women, 68%) attending the HIV clinic of the Yaounde General Hospital in Cameroon. Renal and urinalysis parameters were measured and the Student t-test and Fischer exact test were used to compare the groups of participants. The mean age and CD4 count were, respectively, 35 +/- 10.7 years and 305 +/- 202/mL. Fifty-six (54%) patients presented with stages 3 and 4 of HIV infection. Forty-three (41%) patients had urinalysis abnormalities, including proteinuria (36%), leukocyturia (13%) and hematuria (12%). Proteinuria was associated with increased age, advanced stage of HIV infection, decreased CD4 count, hematuria and renal failure (P <0.04). Hematuria and leukocyturia were associated with decreased CD4 count and advanced stage of HIV infection, respectively (P = 0.04). The mean estimated glomerular filtration (eGFR) rate was 100.2 +/- 32.7 mL/min; three (3%) patients had renal failure (eGFR <60 mL/min) and 45 (43%) patients had reduced kidney function 60 <=eGFR <=90 mL/min. There was a high prevalence of decreased kidney function and proteinuria among Cameroonian HIV-infected patients naive to HAART. Indicators of the severity of HIV infection, including advanced stage and low CD4 count, were associated with urinalysis abnormalities. PMID- 24231507 TI - Pharmacogenomics of cantharidin in tumor cells. AB - Cantharis vesicatoria (blister beetle) is used in Chinese medicine and has been categorized as highly toxic in the Chinese pharmacopeia. In Europe, Cantharis patches have been used since ages to treat various skin-related diseases. We investigated the cytotoxicity of the Cantharis ingredient, cantharidin, in 41 tumor cell lines (Oncotest panel) and compared the results with those of 60 cell lines of the National Cancer Institute, USA. We found profound activity at low micromolar concentrations (log 10IC50 values between -6.980 and 5.009 M). Cantharidin bound to protein phosphatase 2A (PP2A) with higher affinity (-8.12 kcal/mol) than to PP1 (-6.25 kcal/mol) in molecular docking analyses. Using a PCR array for 84 apoptosis genes, cantharidin treatment upregulated gene expression of caspase-1 and nerve growth factor receptor, but downregulated mRNA expression of Bcl-2 like protein 10, Fas ligand, and tumor necrosis factor-alpha. By using COMPARE analysis of microarray-based transcriptome-wide mRNA expressions, 21 genes were found to significantly correlate with response of 60 tumor cell lines to cantharidin. As shown by hierarchical cluster analysis and chi-squared test, the distribution of cell lines in the dendrogram according to their gene expression profiles predicted sensitivity or resistance to cantharidin (P=6.482 * 10(-5)). The compassionate use of Cantharis patches in two patients suffering from basalioma and Mycosis fungoides, respectively, considerably improved the diseases without signs of toxicity. In conclusion, these results indicate that cantharidin may be a useful candidate to develop novel strategies for cancer therapy. PMID- 24231508 TI - Monosaccharide digitoxin derivative sensitize human non-small cell lung cancer cells to anoikis through Mcl-1 proteasomal degradation. AB - Advanced stage cancers acquire anoikis resistance which provides metastatic potential to invade and form tumors at distant sites. Suppression of anoikis resistance by novel molecular therapies would greatly benefit treatment strategies for metastatic cancers. Recently, digitoxin and several of its novel synthetic derivatives, such as alpha-l-rhamnose monosaccharide derivative (D6 MA), have been synthesized and studied for their profound anticancer activity in various cancer cell lines. In this study, we investigated the anoikis sensitizing effect of D6-MA compared with digitoxin to identify their anti-metastatic mechanism of action. D6-MA sensitized NSCLC H460 cells to detachment-induced apoptosis with significantly greater cytotoxicity (IC50=11.9 nM) than digitoxin (IC50=90.7 nM) by activating caspase-9. Screening of the Bcl-2 protein family revealed that degradation of anti-apoptotic Mcl-1 protein is a favorable target. Mcl-1 over-expression and knockdown studies in D6-MA and digitoxin exposed cells resulted in rescue and enhancement, respectively, indicating a facilitative role for decreased Mcl-1 expression in NSCLC anoikis. Transfection with mutant Mcl 1S159 attenuated detachment-induced cell death and correlated with a remaining of Mcl-1 level. Furthermore, D6-MA suppressed Mcl-1 expression via ubiquitin proteasomal degradation that is dependent on activation of glycogen synthase kinase (GSK)-3beta signaling. In addition, D6-MA also targeted Mcl-1 degradation causing an increased anoikis in A549 lung cancer cells. Anoikis sensitizing effect on normal small airway epithelial cells was not observed indicating the specificity of D6-MA and digitoxin for NSCLC. These results identify a novel cardiac glycoside (CG) sensitizing anoikis mechanism and provide a promising anti metastatic target for lung cancer therapy. PMID- 24231509 TI - Atypical protein kinase Ciota as a human oncogene and therapeutic target. AB - Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family. The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions. Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer. PMID- 24231512 TI - Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression. AB - The purpose of the present study was to investigate the potential of Venlafaxine loaded alginate nanoparticles (VLF AG-NPs) for treatment of depression via intranasal (i.n.) nose to brain delivery route. The VLF AG-NPs were prepared and optimized on the basis of various physio-chemical characteristics. Pharmacodynamic studies of the VLF AG-NPs for antidepressant activity were carried in-vivo by forced swimming test and locomotor activity test on albino Wistar rats. VLF AG-NPsi.n. treatment significantly improved the behavioural analysis parameters i.e. swimming, climbing, and immobility in comparison to the VLF solutioni.n. and VLF tabletoral. The intranasal VLF AG-NPs also improved locomotor activity when compared with VLF solutioni.n. and VLF tabletoral. Confocal laser scanning fluorescence microscopy studies were performed on isolated organs of rats after intravenous and intranasal administrations of Rodamine-123 loaded alginate nanoparticles to determine its efficacy for nose to brain delivery and also for its qualitative distribution to other organs. Brain uptake and pharmacokinetic studies were performed by determination of VLF concentration in blood and brain respectively for VLF AG-NPsi.n., VLF solutioni.n. and VLF solutioni.v. The greater brain/blood ratios for VLF AG NPsi.n. in comparison to VLF solutioni.n. and VLF solutioni.v. respectively at 30 min are indicative of superiority of alginate nanoparticles for direct nose to brain transport of VLF. Thus, VLF AG-NPsi.n. delivered greater VLF to the brain in comparison to VLF solution which indicates that VLF AG-NPs could be a promising approach for the treatment of depression. PMID- 24231511 TI - Angiotensin (1-7) protects against stress-induced gastric lesions in rats. AB - Stress ulcers can develop with severe physiological stress, and have been proposed as being brain-driven events. New findings continue to suggest that stress ulcers can be more effectively managed through central manipulation rather than by simply altering local gastric factors. Angiotensin (1-7) (Ang (1-7)) is present as an endogenous constituent of the brain and stomach. The beneficial effects of Ang (1-7) have been confirmed in the vessels, brain, heart, kidney, liver and lungs, but not in the stomach. Given the accumulating evidence suggesting the anti-stress activities of Ang (1-7), its potential gastroprotective effect in the context of stress requires further investigation. In the present study, rat gastric mucosal lesions were induced by 2h of cold restraint stress. We observed that these lesions were significantly attenuated after 1 week of intracerebroventricular treatment with Ang (1-7). This gastroprotective effect was associated with attenuated oxidative stress and suppressed acid secretion. Brain Ang (1-7) administration profoundly modified responses to stress, indicated by altered levels of several stress hormones, including Ang II, glucocorticoid, norepinephrine, serotonin, and dopamine, in blood or stress-related brain regions. These findings indicate that Ang (1-7) exerts anti-stress activities by restoring the gastric microenvironment and modulating the stress pathways. Ang (1-7) may be a promising agent for stress ulcer prophylaxis and therapy, administered through brain-permeable mimics or carriers. PMID- 24231510 TI - Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets. AB - Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative and nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin. PMID- 24231513 TI - Modified ventilatory response characteristics to exercise in breath-hold divers. AB - Specific adjustments to repeated extreme apnea are not fully known and understood. While a blunted ventilatory chemosensitivity to CO2 is described for elite breath-hold divers (BHDs) at rest, it is unclear whether specific adaptations affect their response to dynamic exercise. Eight elite BHDs with a previously validated decrease in CO2 chemosensitivity, 8 scuba divers (SCDs), and 8 matched control subjects were included in a study where markers of ventilatory response, Fowler's dead space, partial pressure of carbon dioxide (pCO2), and blood lactate concentrations during cycle exercise were measured. Maximal power output did not differ between the groups, but lactate threshold (thetaL) appeared at a significantly lowered respiratory compensation point (RCP) and at a higher VO2 for the BHDs. End-tidal (petCO2) and estimated arterial pCO2 (paCO2) were significantly higher in BHDs at thetaL, the RCP, and maximum exhaustion. BHDs showed a significantly (P < .01) slower breathing pattern in relation to a given tidal volume at a specific work rate. In summary, BHDs presented signs of a metabolic shift from aerobic to anaerobic energy supply, decreased chemosensitivity during exercise, and a distinct ventilatory-response pattern during cycle exercise that differs from SCDs and controls. PMID- 24231514 TI - Evaluation of optimal concentration and exposure duration of valproic acid alone or in combination with ViraDuctin to augment adenovirus transduction in human adipose stem cells. AB - BACKGROUND AIMS: Recombinant adenoviruses have tremendous potential in both gene therapy research and therapeutic applications. Mesenchymal stromal cells have a set of several properties that make them ideally suited for both regenerative medicine and gene and drug delivery. A limitation of adenoviral-mediated gene transfer is indeed the poor transduction rate of cells with low or no levels of the specific adenoviral cell surface receptor coxsackie virus and adenovirus receptor (CAR), such as human mesenchymal stromal cells. In the present work, we tried to increase the adenovirus transduction level and mediated gene delivery of human adipose stem cells with the use of valproic acid (VPA) and determined the proper concentration and duration of treatment alone or in combination with ViraDuctin adenovirus transduction reagent. METHODS: Green fluorescent protein expressing recombinant adenovirus was propagated. The effects of various doses and exposure periods of VPA on CAR expression in human adipose stem cells were speculated by quantitative real-time polymerase chain reaction and adenoviral transduction rate by flow cytometry in different doses and time intervals of VPA and in combination with ViraDuctin transduction reagent. RESULTS: CAR messenger RNA upregulation through VPA was observed in human adipose stem cells; it was a dependent factor of dose and exposure time. Consequently, adenoviral transduction level of human adipose stem cells treated with VPA was increased, and co administration of VPA and ViraDuctin further enhanced the transduction rate. CONCLUSIONS: These results confirm that addition of VPA to hASCs alone or in combination with ViraDuctin has enhancing effects on adenoviral transduction rate, which can be auspicious in adenoviral-mediated gene therapy. PMID- 24231515 TI - Enrichment isolation of adipose-derived stem/stromal cells from the liquid portion of liposuction aspirates with the use of an adherent column. AB - BACKGROUND AIMS: Adipose-derived stem/progenitor cells (ASCs) are typically obtained from the lipoaspirates; however, a smaller number of ASCs can be isolated without enzymatic digestion from the infranatant liposuction aspirate fluid (LAF). We evaluated the effectiveness of an adherent column, currently used to isolate mesenchymal stromal cells from bone marrow, to isolate LAF cells. METHODS: We applied peripheral blood (PB), PB mixed with cultured ASCs (PB-ASC), and LAF solution to the column and divided it into two fractions, the adherent (positive) and the non-adherent (negative) fractions. We compared this method with hypotonic hemolysis (lysis) for the red blood cell count, nucleated cells count and cell compositions as well as functional properties of isolated mesenchymal cells. RESULTS: The column effectively removed red blood cells, though the removal efficiency was slightly inferior to hemolysis. After column processing of PB-ASC, 60.5% of ASCs (53.2% by lysis) were selectively collected in the positive fraction, and the negative fraction contained almost no ASCs. After processing of LAF solution, nucleated cell yields were comparable between the column and hemolysis; however, subsequent adherent culture indicated that a higher average ASC yield was obtained from the column-positive samples than from the lysis samples, suggesting that the column method may be superior to hemolysis for obtaining viable ASCs. Mesenchymal differentiation and network formation assays showed no statistical differences in ASC functions between the lysis and column-positive samples. CONCLUSIONS: Our results suggest that a column with non woven rayon and polyethylene fabrics is useful for isolating stromal vascular fraction cells from LAF solutions for clinical applications. PMID- 24231516 TI - Commentary on a paper by Verbeni et al. PMID- 24231518 TI - Heritability of brain volumes in older adults: the Older Australian Twins Study. AB - The relative contributions of genetic and environmental factors to brain structure change throughout the lifespan. Brain structures have been reported to be highly heritable in middle-aged individuals and younger; however, the influence of genes on brain structure is less studied in older adults. We performed a magnetic resonance imaging study of 236 older twins, with a mean age of 71.4 +/- 5.7 years, to examine the heritability of 53 brain global and lobar volumetric measures. Total brain volume (63%) and other volumetric measures were moderately to highly heritable in late life, and these genetic influences tended to decrease with age, suggesting a greater influence of environmental factors as age advanced. Genetic influences were higher in men and on the left hemisphere compared with the right. In multivariate models, common genetic factors were observed for global and lobar total and gray matter volumes. This study examined the genetic contribution to 53 brain global and lobar volumetric measures in older twins for the first time, and the influence of age, sex, and laterality on these genetic contributions, which are useful information for a better understanding of the process of brain aging and helping individuals to have a healthy aging. PMID- 24231517 TI - Cell targeting by the Staphylococcus aureus pore-forming toxins: it's not just about lipids. AB - Staphylococcus aureus employs numerous pore-forming cytotoxins to injure host immune cells and promote infection. Until recently, it was unclear how these cytotoxins targeted specific cell types for lysis. Membrane lipids were initially postulated to be cytotoxin receptor candidates. However, the cell-type specificity and species-dependent targeting of these toxins did not support lipids as sole receptors. The recent identification of proteinaceous receptors for several S. aureus cytotoxins now provides an explanation for the observed tropism. These findings also have important implications for the implementation of animal models to study S. aureus pathogenesis, and for the development of novel therapeutics. PMID- 24231519 TI - Cardiovascular disease contributes to Alzheimer's disease: evidence from large scale genome-wide association studies. AB - Alzheimer's disease (AD) is the most common and complex neurodegenerative disease in the elderly individuals. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. These GWAS have yielded important new insights into the genetic mechanisms of AD. However, these newly identified AD susceptibility loci exert only very small risk effects and cannot fully explain the underlying AD genetic risk. We hypothesize that combining the findings from different AD GWAS may have greater power than genetic analysis alone. To identify new AD risk factors, we integrated findings from 3 previous large-scale AD GWAS (n = 14,138) using a gene-based meta-analysis and subsequently conducted a pathway analysis using the kyoto encyclopedia of genes and genomes and gene ontology databases. Interestingly, we not only confirmed previous findings, but also highlighted, for the first time, the involvement of cardiovascular disease related pathways in AD. Our results provided the clues as to the link between these diseases using pathway analysis methods. We believe that these findings will be very useful for future genetic studies of AD. PMID- 24231521 TI - Side-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model. AB - BACKGROUND: Peripheral nerve injury can result in muscle atrophy and long-term disability. We hypothesize that creating a side-to-side bridge to link an injured nerve with a healthy nerve will reduce muscle atrophy and improve muscle function. METHODS: Sprague-Dawley rats were divided into four groups (n = 7 per group). Group 1: transection only--a 10-mm gap was created in the proximal tibial nerve; group 2: transected plus repaired--the transected tibial nerve was repaired; group 3: transected plus repaired plus nerve bridge--transected nerve repaired with a distal nerve bridge between the tibial and peroneal nerves via epineurial windows; and group 4: transected plus nerve bridge--transected tibial nerve left unrepaired and distal bridge added. Gait was assessed every 2 wk. At 90 d the following measures were determined: gastrocnemius mass, muscle and nerve nuclear density, and axonal infiltration into the nerve bridge. RESULTS: Groups 3 and 4 had greater improvements in walking track recovery than groups 1 and 2. Group 3's gastrocnemius muscles exhibited the least amount of atrophy. Groups 1, 2, and 4 exhibited greater histologic appearance of muscle breakdown compared with group 3 and control muscle. Finally, most bridges in groups 3 and 4 had neuronal sprouting via the epineurial windows. CONCLUSIONS: Our study demonstrated reduced muscle atrophy with a side-to-side nerve bridge in the setting of peripheral nerve injury. These results support the application of novel side-to-side bridges in combination with traditional end-to-end neurorrhaphy to preserve muscle viability after peripheral nerve injuries. PMID- 24231520 TI - An unanticipated early function of DEAD-box ATPase Prp28 during commitment to splicing is modulated by U5 snRNP protein Prp8. AB - The stepwise assembly of the highly dynamic spliceosome is guided by RNA dependent ATPases of the DEAD-box family, whose regulation is poorly understood. In the canonical assembly model, the U4/U6.U5 triple snRNP binds only after joining of the U1 and, subsequently, U2 snRNPs to the intron-containing pre-mRNA. Catalytic activation requires the exchange of U6 for U1 snRNA at the 5' splice site, which is promoted by the DEAD-box protein Prp28. Because Prp8, an integral U5 snRNP protein, is thought to be a central regulator of DEAD-box proteins, we conducted a targeted search in Prp8 for cold-insensitive suppressors of a cold sensitive Prp28 mutant, prp28-1. We identified a cluster of suppressor mutations in an N-terminal bromodomain-like sequence of Prp8. To identify the precise defect in prp28-1 strains that is suppressed by the Prp8 alleles, we analyzed spliceosome assembly in vivo and in vitro. Surprisingly, in the prp28-1 strain, we observed a block not only to spliceosome activation but also to one of the earliest steps of assembly, formation of the ATP-independent commitment complex 2 (CC2). The Prp8 suppressor partially corrected both the early assembly and later activation defects of prp28-1, supporting a role for this U5 snRNP protein in both the ATP-independent and ATP-dependent functions of Prp28. We conclude that the U5 snRNP has a role in the earliest events of assembly, prior to its stable incorporation into the spliceosome. PMID- 24231522 TI - Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia-reperfusion through Adenosine 5' monophosphate-activated protein kinase-sirtuin1 pathway. AB - BACKGROUND: Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia reperfusion (I/R). Omega-3 polyunsaturated fatty acid (omega-3 PUFA) is a potent activator of the Adenosine 5'-monophosphate-activated protein kinase-sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether omega-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway. METHODS: Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as omega-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis. RESULTS: Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor kappaB, tumor necrosis factor alpha, interleukin 6, and interleukin 1beta), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs. CONCLUSIONS: Pretreatment with omega-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R-induced ALI. PMID- 24231523 TI - Temperature-dependent thermal conductivities of 1D semiconducting nanowires via four-point-probe 3-omega method. AB - We report on a systematic study of the thermal transport characteristics of both as-grown zinc oxide and gallium nitride nanowires (NWs) via the four-point-probe 3-omega method in the temperature range 130-300 K. Both as-grown NWs were synthesized by a vapor-liquid-solid growth mechanism, and show clear n-type semiconducting behavior without any defects, which enables both the NWs to be promising candidates for thermoelectric materials. To measure the thermal conductivities of both NWs with lower heat loss and measurement errors, the suspended structures were formed by a combination of an e-beam lithography process and a random dispersion method. The measured thermal conductivities of both NWs are greatly reduced compared to their bulk materials due to the enhanced phonon scattering via the size effect and dopants (impurities). Furthermore, we observed that the Umklapp peaks of both NWs are shifted to a higher temperature than those of their bulk counterparts, indicating that phonon-boundary scattering dominates over other phonon scattering due to the size effect. PMID- 24231524 TI - Evaluation of the California Safer Consumer Products Regulation and the impact on consumers and product manufacturers. AB - Chemistry enables more than 95% of products in the marketplace. Over the past 20 years, various entities began to generate inventories of chemicals ("chemical watch lists") potentially associated with human or environmental health risks. Some lists included thousands of chemicals, while others listed only a few chemistries with limited properties or toxicological endpoints (e.g., neurotoxicants). Enacted on October 1, 2013, the California Safer Consumer Products Regulation (SCP) utilized data from chemical inventory lists to create one master list. This paper aims to discuss the background and requirements of this regulation. Additionally, we wanted to understand the universe of Candidate Chemicals identified by the Regulation. Data from all 23 chemical lists identified in the SCP Regulation were entered into a database. The most prevalent chemicals among the ~2900 chemicals are identified, including the most prevalent chemical, lead, appearing on 65% of lists, followed by DEHP (52%), perchloroethylene (48%), and benzene (48%). Our results indicated that the most prevalent Candidate Chemicals were either persistent, bioaccumulative, carcinogenic, or reprotoxic. This regulation will have wide-ranging impact in California and throughout the global supply chain, which is highlighted through selected examples and case studies. PMID- 24231525 TI - Oral toxicity of silver ions, silver nanoparticles and colloidal silver--a review. AB - Orally administered silver has been described to be absorbed in a range of 0.4 18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached. PMID- 24231526 TI - Oxymatrine induces apoptosis in human cervical cancer cells through guanine nucleotide depletion. AB - Oxymatrine is an alkaloid obtained primarily from Sophora roots and has been shown to show anticancer effects in various cancers. However, the cellular and molecular effects of this agent on cervical cancer have been poorly characterized. Here, we investigated the antitumor effect of oxymatrine on a human cervical cancer cell line (HeLa). Our results showed that application of oxymatrine significantly inhibited the cell growth and tumorigenesis in a dose dependent manner and induced apoptosis through caspase-dependent pathways as determined using flow cytometry and TUNEL staining analysis. To define the proteins potentially related to the mechanisms of action, proteomic analysis was utilized to detect proteins altered by oxymatrine. As the downregulated gene, inosine monophosphate dehydrogenase type II (IMPDH2) was responsible for oxymatrine-induced mitochondrial-related apoptosis. Moreover, oxymatrine depleted intracellular guanosine 5'-triphosphate (GTP) levels by effective IMPDH inhibition. Functional analyses further showed that oxymatrine and tiazofurin, an inhibitor of IMPDH2, sensitized resistant HeLa/DDP cells to cisplatin. In addition, the expression of IMPDH2 in cervical cancer was significantly higher than that in the normal cervical epithelium. Taken together, these findings suggest that targeting of IMPDH2 by potential pharmacological inhibitors, oxymatrine in combination with chemotherapy, might be a promising means of overcoming chemoresistance in cervical cancer with high IMPDH2 expression, and may thus provide new insights into the mechanism of oxyamtrine-induced anticancer effects. PMID- 24231527 TI - Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. AB - Multidrug resistance remains a major obstacle in the effective treatment of metastatic breast cancer. One mechanism by which multidrug resistance is conferred is the decreased intracellular drug accumulation due to the upregulation of the ATP-binding cassette (ABC) transporters. We have previously demonstrated that jadomycins, polyketide-derived natural products produced by Streptomyces venezuelae ISP5230, inhibit the growth of the human breast ductal carcinoma cell lines T47D and MDA-MB-435. To expand our understanding of jadomycin pharmacology, the goal of the present study was to determine whether the function of ABC efflux transporters affects the anticancer activity of jadomycins to MCF7 breast cancer cells. Seven jadomycin analogs (DNV, B, L, SPhG, F, S, and T) effectively reduced the viability of MCF7 control and ABCB1-, ABCC1 , or ABCG2-overexpressing drug-resistant MCF7 breast cancer cells as measured by methyltetrazolium cell viability assays and lactate dehydrogenase cytotoxicity assays. The inhibition of ABCB1, ABCC1, or ABCG2 with verapamil, MK-571, or Ko 143, respectively, did not augment the cytotoxicity of jadomycins DNV, B, L, SPhG, F, S, or T in drug-resistant MCF7 cells. Furthermore, jadomycins B, L, SPhG, F, S, and T did not increase the intracellular accumulation of ABCB1, ABCC1, or ABCG2 fluorescent substrates in HEK-293 cells stably transfected with ABCB1, ABCC1, or ABCG2. We conclude that jadomycins B, L, SPhG, F, S, and T are effective agents in the eradication of MCF7 breast cancer cells grown in culture, and that their cytotoxicities are minimally affected by ABCB1, ABCC1, and ABCG2 efflux transporter function. PMID- 24231529 TI - Blood Cells, Molecules, and Diseases: Past, present, and future. PMID- 24231528 TI - Significance of CD66c expression in childhood acute lymphoblastic leukemia. AB - Upon analyzing 696 childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) cases, we identified the characteristics of CD66c expression. In addition to the confirmation of strong correlation with BCR-ABL positivity and hyperdiploid, we further observed that CD66c is frequently expressed in CRLF2-positive (11/15, p<0.01 against chimeric gene-negative) as well as hypodiploid cases (3/4), whereas it is never expressed in ETV6-RUNX1, MLL-AF4, MLL-AF9, MLL-ENL, and E2A PBX1-positive cases. Although the expression of CD66c itself is not directly linked to the prognosis, the accompanying genetic abnormalities are important prognostic factors for BCP-ALL, indicating the importance of CD66c expression in the initial diagnosis of BCP-ALL. PMID- 24231530 TI - Development and translation of histotripsy: current status and future directions. AB - PURPOSE OF REVIEW: The aim of this article is to outline the initial development of histotripsy, a noninvasive image-guided focused ultrasound technology that mechanically homogenizes targeted tissues and to describe the results of preclinical translational research directed toward urologic applications. RECENT FINDINGS: Histotripsy tissue ablation is based on initiation and control of acoustic cavitation at a target point within the body. This unique mechanical mechanism of action is distinct when compared with conventional thermal ablative modalities. Features of histotripsy (nonthermal, noninvasive, high precision, real-time monitoring/feedback, and tissue liquefaction) have prompted assessment of this technology as a potential ablative therapy for a number of organs and disease processes. SUMMARY: Ongoing research efforts to apply histotripsy to preclinical models of benign prostatic hyperplasia, prostate cancer, renal masses, and renal calculi have resulted in enhanced understanding of cavitation bioeffects, refinement of treatment systems, strategies to enhance treatment efficiency, and initiation of a pilot human clinical trial to assess the safety of histotripsy for benign prostatic hyperplasia therapy. PMID- 24231531 TI - Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard? AB - PURPOSE OF REVIEW: The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is based on alpha blockers and 5alpha-reductase inhibitors isolated or in combination. Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical paradigm is being challenged by antimuscarinics, 5 phosphodiesterase inhibitors (PDE5i) and beta3-adrenoreceptor agonists. RECENT FINDINGS: Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head comparison of tadalafil 5 mg/day with tamsulosin 0.4 mg/day showed that these agents provided the same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact, previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not tamsulosin improved sexual function. Mirabegron, the first beta3-adrenoreceptor agonist, while improving BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure. SUMMARY: The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination. In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept of standard treatment for BPH/LUTS. PMID- 24231532 TI - Effects of the emotion system on adaptive behavior. AB - A central simplifying assumption in evolutionary behavioral ecology has been that optimal behavior is unaffected by genetic or proximate constraints. Observations and experiments show otherwise, so that attention to decision architecture and mechanisms is needed. In psychology, the proximate constraints on decision making and the processes from perception to behavior are collectively described as the emotion system. We specify a model of the emotion system in fish that includes sensory input, neuronal computation, developmental modulation, and a global organismic state and restricts attention during decision making for behavioral outcomes. The model further includes food competition, safety in numbers, and a fluctuating environment. We find that emergent strategies in evolved populations include common emotional appraisal of sensory input related to fear and hunger and also include frequency-dependent rules for behavioral responses. Focused attention is at times more important than spatial behavior for growth and survival. Spatial segregation of the population is driven by personality differences. By coupling proximate and immediate influences on behavior with ultimate fitness consequences through the emotion system, this approach contributes to a unified perspective on the phenotype, by integrating effects of the environment, genetics, development, physiology, behavior, life history, and evolution. PMID- 24231533 TI - Reciprocal behavioral plasticity and behavioral types during predator-prey interactions. AB - How predators and prey interact has important consequences for population dynamics and community stability. Here we explored how predator-prey interactions are simultaneously affected by reciprocal behavioral plasticity (i.e., plasticity in prey defenses countered by plasticity in predator offenses and vice versa) and consistent individual behavioral variation (i.e., behavioral types) within both predator and prey populations. We assessed the behavior of a predator species (northern pike) and a prey species (three-spined stickleback) during one-on-one encounters. We also measured additional behavioral and morphological traits in each species. Using structural equation modeling, we found that reciprocal behavioral plasticity as well as predator and prey behavioral types influenced how individuals behaved during an interaction. Thus, the progression and ultimate outcome of predator-prey interactions depend on both the dynamic behavioral feedback occurring during the encounter and the underlying behavioral type of each participant. We also examined whether predator behavioral type is underlain by differences in metabolism and organ size. We provide some of the first evidence that behavioral type is related to resting metabolic rate and size of a sensory organ (the eyes). Understanding the extent to which reciprocal behavioral plasticity and intraspecific behavioral variation influence the outcome of species interactions could provide insight into the maintenance of behavioral variation as well as community dynamics. PMID- 24231534 TI - Is sex advantageous in adverse environments? A test of the abandon-ship hypothesis. AB - Understanding the evolution and maintenance of sexual reproduction remains a long standing challenge in evolutionary biology. Stress often induces sexual reproduction in facultatively sexual species (those species capable of both sexual and asexual reproduction). The abandon-ship hypothesis predicts higher allocation to sex under stress to allow low-fitness individuals to recombine their genotype, potentially increasing offspring fitness. However, effective tests of the abandon-ship hypothesis, particularly in multicellular organisms, are lacking. Here we test the abandon-ship hypothesis, using cyanogenic and acyanogenic defense phenotypes of the short-lived perennial herb Trifolium repens. Cyanogenesis provides an effective defense against herbivores and is under relatively simple genetic control (plants dominant for cyanogenesis at two alleles express the defended phenotype). Thus, maladapted individuals can acquire adaptive defense alleles for their offspring in a single episode of sexual reproduction. Plants were grown under high- and low-herbivory treatments (plants were exposed to herbivorous snails) and a control treatment (no herbivory). Herbivores reduced growth and fitness in all treated plants, but herbivory induced higher sexual allocation only in maladapted (acyanogenic) individuals. Overall, our results support the abandon-ship hypothesis. PMID- 24231535 TI - Behavioral and morphological traits interact to promote the evolution of alternative reproductive tactics in a lizard. AB - Alternative reproductive tactics (ARTs) are predicted to be the result of disruptive correlational selection on suites of morphological, physiological, and behavioral traits. ARTs are most obvious when they occur in discrete morphs with concomitant behavioral tactics. However, ARTs driven by behavior in species lacking obvious phenotypic differences are rarely documented and poorly understood. We quantified selection acting on phenotypic traits predicted to characterize ARTs by observing marked lizards in six seminatural populations. We quantified reproductive fitness for each male using six microsatellite DNA loci from 226 offspring born to 56 females. Candidate models containing directional and correlational selection gradients were equally supported. As predicted, large males with large home ranges and large males that were observed frequently had the highest reproductive success. We also found evidence that large males that moved little but that were observed frequently and large males that moved frequently but that were observed little were predicted to have high fitness. Model predictions support our verbal hypothesis regarding the phenotypes characterizing ARTs and suggest that large males may be adopting subtly different tactics to acquire paternity. Our results suggest that disruptive correlational selection between behavioral traits may drive the evolution of ARTs in "cryptic" systems that lack overt polymorphisms. PMID- 24231536 TI - How life history influences population dynamics in fluctuating environments. AB - A major question in ecology is how age-specific variation in demographic parameters influences population dynamics. Based on long-term studies of growing populations of birds and mammals, we analyze population dynamics by using fluctuations in the total reproductive value of the population. This enables us to account for random fluctuations in age distribution. The influence of demographic and environmental stochasticity on the population dynamics of a species decreased with generation time. Variation in age-specific contributions to total reproductive value and to stochastic components of population dynamics was correlated with the position of the species along the slow-fast continuum of life-history variation. Younger age classes relative to the generation time accounted for larger contributions to the total reproductive value and to demographic stochasticity in "slow" than in "fast" species, in which many age classes contributed more equally. In contrast, fluctuations in population growth rate attributable to stochastic environmental variation involved a larger proportion of all age classes independent of life history. Thus, changes in population growth rates can be surprisingly well explained by basic species specific life-history characteristics. PMID- 24231537 TI - Linking life-history traits, ecology, and niche breadth evolution in North American eriogonoids (Polygonaceae). AB - Macroevolutionary and microevolutionary studies provide complementary explanations of the processes shaping the evolution of niche breadth. Macroevolutionary approaches scrutinize factors such as the temporal and spatial environmental heterogeneities that drive differentiation among species. Microevolutionary studies, in contrast, focus on the processes that affect intraspecific variability. We combine these perspectives by using macroevolutionary models in a comparative study of intraspecific variability. We address potential differences in rates of evolution of niche breadth and position in annual and perennial plants of the Eriogonoideae subfamily of the Polygonaceae. We anticipated higher rates of evolution in annuals than in perennials owing to differences in generation time that are paralleled by rates of molecular evolution. Instead, we found that perennial eriogonoid species present greater environmental tolerance (wider climate niche) than annual species. Niche breadth of perennial species has evolved two to four times faster than in annuals, while niche optimum has diversified more rapidly among annual species than among perennials. Niche breadth and average elevation of species are correlated. Moreover, niche breadth increases more rapidly with mean species elevation in perennials than in annuals. Our results suggest that both environmental gradients and life-history strategy influence rates and patterns of niche breadth evolution. PMID- 24231538 TI - Despite catch-up, prolonged growth has detrimental fitness consequences in a long lived vertebrate. AB - Individuals experiencing poor growth early in life may later make up their size deficit. Compensatory growth or growth prolongation may lead to such catch-up, involving different life-history trade-offs under natural conditions. Frequent recaptures and detailed monitoring of animals surviving to asymptotic size are required to compare growth tactics and their fitness consequences. No study to date has obtained such detailed information for wild animals. We used repeated mass measurements (mean 11.6/animal) spanning the lifetime of 104 bighorn ewes (Ovis canadensis) to quantify growth tactics and identify the determinants and life-history costs of these tactics. Growth prolongation, not compensatory growth, led to partial catch-up: mass difference at age 7 was reduced to 4%, for two groups that differed by nearly 20% as yearlings. Ewes that had been light as yearlings prolonged their growth regardless of density or age of primiparity. Growth prolongation did not affect fecundity or longevity. Ewes that experienced poor early growth prolonged growth at the expense of reproductive fitness, weaning a smaller proportion of their lambs. By tracking multiyear growth patterns and comparing events at different life-history stages, we quantified a trade-off between growth and reproduction that would be overlooked if only the adult phenotype was considered. Compensatory growth in long-lived animals appears unlikely when early growth restrictions are mostly density dependent. PMID- 24231539 TI - A three-way trade-off maintains functional diversity under variable resource supply. AB - The resources that organisms depend on often fluctuate over time, and a variety of common traits are thought to be adaptations to variable resource supply. To understand the trait structure of communities, it is necessary to understand the functional trade-offs that determine what trait combinations are possible and which species can persist and coexist in a given environment. We compare traits across phytoplankton species in order to test for proposed trade-offs between maximum growth rate, equilibrium competitive ability for phosphorus (P), and ability to store P. We find evidence for a three-way trade-off between these traits, and we use empirical trait covariation to parameterize a mechanistic model of competition under pulsed P supply. The model shows that different strategies are favored under different conditions of nutrient supply regime, productivity, and mortality. Furthermore, multiple strategies typically coexist, and the range of traits that persist in the model is similar to the range of traits found in real species. These results suggest that mechanistic models informed by empirical trait variation, in combination with data on the trait structure of natural communities, will play an important role in uncovering the mechanisms that underlie the diversity and structure of ecological communities. PMID- 24231540 TI - An insect-feeding guild of carnivorous plants and spiders: does optimal foraging lead to competition or facilitation? AB - Carnivorous plants and spiders, along with their prey, are main players in an insect-feeding guild found on acidic, poorly drained soils in disturbed habitat. Darwin's notion that these plants must actively attract the insects they capture raises the possibility that spiders could benefit from proximity to prey hotspots created by the plants. Alternatively, carnivorous plants and spiders may deplete prey locally or (through insect redistribution) more widely, reducing each other's gain rates from predation. Here, we formulate and analyze a model of this guild, parameterized for carnivorous sundews and lycosid spiders, under assumptions of random movement by insects and optimal foraging by predators. Optimal foraging here involves gain maximization via trap investment (optimal web sizes and sundew trichome densities) and an ideal free distribution of spiders between areas with and without sundews. We find no facilitation: spiders and sundews engage in intense exploitation competition. Insect attraction by plants modestly increases sundew gain rates but slightly decreases spider gain rates. In the absence of population size structure, optimal spider redistribution between areas with and without sundews yields web sizes that are identical for all spiders, regardless of proximity to sundews. Web-building spiders have higher gain rates than wandering spiders in this system at high insect densities, but wandering spiders have the advantage at low insect densities. Results are complex, indicating that predictions to be tested empirically must be based on careful quantitative assessment. PMID- 24231541 TI - Timing and number of colonizations but not diversification rates affect diversity patterns in hemosporidian lineages on a remote oceanic archipelago. AB - Parasite diversity on remote oceanic archipelagos is determined by the number and timing of colonizations and by in situ diversification rate. In this study, we compare intra-archipelago diversity of two hemosporidian parasite genera, Plasmodium and Leucocytozoon, infecting birds of the Mascarene archipelago. Despite the generally higher vagility of Plasmodium parasites, we report a diversity of Plasmodium cytochrome b haplotypes in the archipelago much lower than that of Leucocytozoon. Using phylogenetic data, we find that this difference in diversity is consistent with differences in the timing and number of colonizations, while rates of diversification do not vary significantly between the two genera. The prominence of immigration history in explaining current diversity patterns highlights the importance of historical contingencies in driving disparate biogeographic patterns in potentially harmful blood parasites infecting island birds. PMID- 24231542 TI - Density of antennal sensilla influences efficacy of communication in a social insect. AB - Effective communication requires reliable signals and competent receptors. Theoretical and empirical accounts of animal signaling focus overwhelmingly on the capacity of the signaler to convey the message. Nevertheless, the intended receiver's ability to detect a signal depends on the condition of its receptor organs, as documented for humans. The impact of receptor organ condition on signal reception and its consequences for functional behavior are poorly understood. Social insects use antennae to detect chemical odors that distinguish between nestmates and enemies, reacting aggressively to the latter. We investigated the impact of antennal condition, determined by the density of sensilla, on the behavior of the weaver ant Oecophylla smaragdina. Worker aggression depended upon the condition of their antennae: workers with fewer sensilla on their antennae reacted less aggressively to nonnestmate enemies. These novel data highlight the largely unappreciated significance of receptor organ condition for animal communication and may have implications for coevolutionary processes in animal communication. PMID- 24231545 TI - Body size and extinction risk in terrestrial mammals above the species level. AB - Mammalian body mass strongly correlates with life history and population properties at the scale of mouse to elephant. Large body size is thus often associated with elevated extinction risk. I examined the North American fossil record (28-1 million years ago) of 276 terrestrial genera to uncover the relationship between body size and extinction probability above the species level. Phylogenetic comparative analysis revealed no correlation between sampling adjusted durations and body masses ranging 7 orders of magnitude, an observation that was corroborated by survival analysis. Most of the ecological and temporal groups within the data set showed the same lack of relationship. Size-biased generic extinctions do not constitute a general feature of the Holarctic mammalian faunas in the Neogene. Rather, accelerated loss of large mammals occurred during intervals that experienced combinations of regional aridification and increased biomic heterogeneity within continents. The latter phenomenon is consistent with the macroecological prediction that large geographic ranges are critical to the survival of large mammals in evolutionary time. The frequent lack of size selectivity in generic extinctions can be reconciled with size-biased species loss if extinctions of large and small mammals at the species level are often driven by ecological perturbations of different spatial and temporal scales, while those at the genus level are more synchronized in time as a result of fundamental, multiscale environmental shifts. PMID- 24231546 TI - Three modes of adaptive speciation in spatially structured populations. AB - Adaptive speciation with gene flow via the evolution of assortative mating has classically been studied in one of two different scenarios. First, speciation can occur if frequency-dependent competition in sympatry induces disruptive selection, leading to indirect selection for mating with similar phenotypes. Second, if a subpopulation is locally adapted to a specific environment, then there is indirect selection against hybridizing with maladapted immigrants. While both of these mechanisms have been modeled many times, the literature lacks models that allow direct comparisons between them. Here we incorporate both frequency-dependent competition and local adaptation into a single model and investigate whether and how they interact in driving speciation. We report two main results. First, we show that individually, the two mechanisms operate under separate conditions, hardly influencing each other when one of them alone is sufficient to drive speciation. Second, we also find that the two mechanisms can operate together, leading to a third speciation mode in which speciation is initiated by selection against maladapted migrants but completed by within-deme competition in a distinct second phase. While this third mode bears some similarity to classical reinforcement, it is considerably faster, and both newly formed species go on to coexist in sympatry. PMID- 24231547 TI - Patterns of host-parasite adaptation in three populations of monarch butterflies infected with a naturally occurring protozoan disease: virulence, resistance, and tolerance. AB - Many studies have used host-parasite systems to study local adaptation, but few of these studies have found unequivocal evidence for adaptation. One potential reason is that most studies have focused on limited measures of host and parasite fitness that are generally assumed to be under negative frequency-dependent selection. We have used reciprocal cross-infection experiments to test for local adaptation in Hawaiian, south Floridian, and eastern North American populations of monarch butterflies and their protozoan parasites. Sympatric host-parasite combinations did not result in greater host or parasite fitness, as would be expected under coevolutionary dynamics driven by negative frequency-dependent selection. Instead, we found that Hawaiian hosts were more resistant and carried more infective and virulent parasites, which is consistent with theoretical predictions for virulence evolution and coevolutionary arms race dynamics. We also found that Hawaiian hosts were more tolerant, particularly of Hawaiian parasites, indicating that increased resistance does not preclude increased tolerance within a population and that hosts may be more tolerant of local parasites. We did not find a similar pattern in the south Floridian or eastern populations, possibly because host-parasite adaptation occurs within the context of a greater ecological community. PMID- 24231548 TI - High dose rate brachytherapy boost for prostate cancer: a systematic review. AB - Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk stratification, expected outcomes, toxicities, quality of life, and cost. PMID- 24231549 TI - Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. PMID- 24231550 TI - Time-frequency characteristics and dynamics of sleep spindles in WAG/Rij rats with absence epilepsy. AB - In rat models of absence epilepsy, epileptic spike-wave discharges appeared in EEG spontaneously, and the incidence of epileptic activity increases with age. Spike-wave discharges and sleep spindles are known to share common thalamo cortical mechanism, suggesting that absence seizures might affect some intrinsic properties of sleep spindles. This paper examines time-frequency EEG characteristics of anterior sleep spindles in non-epileptic Wistar and epileptic WAG/Rij rats at the age of 7 and 9 months. Considering non-stationary features of sleep spindles, EEG analysis was performed using Morlet-based continuous wavelet transform. It was found, first, that the average frequency of sleep spindles in non-epileptic Wistar rats was higher than in WAG/Rij (13.2 vs 11.2 Hz). Second, the instantaneous frequency ascended during a spindle event in Wistar rats, but it was constant in WAG/Rij. Third, in WAG/Rij rats, the number and duration of epileptic discharges increased in a period between 7 and 9 months of age, but duration and mean value of intra-spindle frequency did not change. In general, age-dependent aggravation of absence seizures in WAG/Rij rats did not affect EEG properties of sleep spindles; it was suggested that pro-epileptic changes in thalamo-cortical network in WAG/Rij rats might prevent dynamic changes of sleep spindles that were detected in Wistar. PMID- 24231552 TI - Spinal distribution of c-Fos activated neurons expressing enkephalin in acute and chronic pain models. AB - The endogenous opioid enkephalin is known to inhibit spinal nociceptive transmission. Here we investigated activation of spinal enkephalinergic neurons by determining the proportions of c-Fos expressing (activated) spinal neurons that were enkephalinergic after different acute and chronic peripheral nociceptive stimuli. The number of c-Fos-activated neurons in the dorsal horn was increased after hind paw injection of capsaicin, formalin or complete Freund's adjuvant (CFA, 1.5 hrs - 4 days). The numbers of these neurons that were enkephalinergic increased after paraformaldehyde, and at 20 hrs, but not 1.5 hrs or 4 days post-CFA as compared to saline. In the spared nerve injury (SNI) model of neuropathic pain, c-Fos expression was increased acutely (2 hrs) and chronically (2 weeks), and a greater number of these were enkephalinergic in the nerve-injured animals acutely compared to controls (sham-SNI). Combining all acute (=2 hrs) versus chronic (>=20 hrs) treatment groups, there was a significant decrease in the percentage of activated neurons that were enkephalinergic in superficial layers, but a significant increase in the deeper layers of the dorsal horn in the chronic treatment group. It is concluded that the overall percentage of c-Fos activated neurons that contained enkephalin was not significantly different between acute and chronic pain phases. However, the shift in localization of these neurons within the spinal dorsal horn indicates a noxious stimulus directed activation pattern. PMID- 24231551 TI - Oxytocin and social cognition in rhesus macaques: implications for understanding and treating human psychopathology. AB - Converging evidence from humans and non-human animals indicates that the neurohypophysial hormone oxytocin (OT) evolved to serve a specialized function in social behavior in mammals. Although OT-based therapies are currently being evaluated as remedies for social deficits in neuropsychiatric disorders, precisely how OT regulates complex social processes remains largely unknown. Here we describe how a non-human primate model can be used to understand the mechanisms by which OT regulates social cognition and thereby inform its clinical application in humans. We focus primarily on recent advances in our understanding of OT-mediated social cognition in rhesus macaques (Macaca mulatta), supplemented by discussion of recent work in humans, other primates, and rodents. Together, these studies endorse the hypothesis that OT promotes social exploration both by amplifying social motivation and by attenuating social vigilance. This article is part of a Special Issue entitled Oxytocin and Social Behav. PMID- 24231553 TI - Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. AB - The Alzheimer's disease (AD) mouse model Tg2576 overexpresses an AD associated mutant variant of human APP and accumulates amyloid beta (Abeta) in an age dependent manner. Using the selective cholinergic immunotoxin mu p75-saporin (SAP), we induced a partial basal forebrain cholinergic degeneration (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Abeta overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory. Conversely, there was no deterioration of cognitive functioning in sham lesioned Tg2576 mice or wild type littermates (wt) receiving the immunotoxin. At 10 months of age, release of acetylcholine (ACh) was addressed by microdialysis in conscious mice. Scopolamine-induced increases in hippocampal ACh efflux was significantly reduced in SAP lesioned Tg2576 mice compared to sham lesioned Tg2576 mice. Intriguingly, there was no significant difference in ACh efflux between wt treatment groups. Following SAP treatment, choline acetyltransferase activity was reduced in the hippocampus and frontal cortex and the reduction was comparable between groups. Our results suggest that partial BFCD acts collectively with increased levels of Abeta to induce cognitive decline and to compromise cholinergic release. Tg2576 mice with BFCD may constitute a new and suitable AD mouse model to study the interrelations between cholinergic deficits and amsyloid deposition. PMID- 24231554 TI - Hormonal contraceptives masculinize brain activation patterns in the absence of behavioral changes in two numerical tasks. AB - The aim of the present study was to identify, whether and how oral hormonal contraceptives (OCs) alter women's number processing. Behavioral performance and brain activation patterns (BOLD-response) of 14 OC-users were evaluated during two distinct numerical tasks (number comparison, number bisection) and compared to 16 men (high testosterone), and 16 naturally cycling women, once during their follicular (low hormone levels) and once during their luteal cycle phase (high progesterone). For both tasks, reliable sex differences and menstrual cycle dependent modulation have previously been described. If progestogenic effects of the synthetic progestins contained in OC play a predominant role, OC-users should be comparable to luteal women. If androgenic effects of the synthetic steroids exert the progestogenic actions, OC-users should be comparable to men. Likewise, if neither of the above are the case, the reduction of endogenous steroids by OCs should make OC-users comparable to follicular women. Our findings suggest that OC users resemble follicular women in their behavioral performance, but show male like brain activation patterns during both tasks. Analysis of brain-behavior relationships suggests that OC-users differ from naturally cycling women in the way they recruit their neural resources to deal with challenges of the tasks. We conclude that OCs, which are used by 100 million women worldwide, may have profound effects on cognition that have not been recognized so far. PMID- 24231555 TI - Concurrent repeated-sprint and resistance training with superimposed vibrations in rugby players. AB - PURPOSE: To examine the effect of repeated-sprint training (RST) vs combined RST and resistance training with superimposed vibrations on repeated-sprint ability (RSA) and lower-body power output in male rugby players. METHODS: Players were divided into 2 training groups. One group performed RST (n = 10) 2 d/wk and the other performed RST 1 d/wk and squat resistance training with superimposed vibrations on the second day (RS+ST; n = 10). The squat training was carried out with a volume similar (ie, number of sets and repetitions) to that of the RST. The training period lasted 6 wk, and it was carried out as a supplement to the regular rugby training sessions. RESULTS: Substantial improvements in RSA mean time (RSA(mean); +2.3%/ES: 0.77 vs +4.1%/ES: 0.91), RSA percent decrement (%Dec; 25.6%/ES: 1.70 vs -23.2%/ES: 0.99), and squat absolute power output (+5.0%/ES:0.36 vs +17.2%/ES: 0.93) were obtained in RST and RS+ST, respectively. Substantial improvements in RSA best time (RSA(best); +2.6%/ES: 0.61) and squat power output normalized to body mass (+18.6%/ES: 0.76) only occurred in RS+ST. Both pretest and posttest RSA(mean) were largely correlated with the RSA(best). However, there were only unclear, small to moderate correlations between individual changes in squat power output and either RSA(mean) or RSA(best). CONCLUSION: Combined RST and resistance training induced improvements of greater magnitude in both repeated-sprint performance and muscle power output than the RST alone. The lack of substantial correlations between individual changes in repeated-sprint and muscle-power performance suggests that the same subjects were not systematically low or high responders to both RST and strength training. PMID- 24231556 TI - Biomarkers of lymphoma in Sjogren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. AB - OBJECTIVES: To define the biomarkers associated with lymphoproliferation in primary Sjogren's syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV). METHODS: A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions. RESULTS: Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive. CONCLUSIONS: Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution. PMID- 24231557 TI - Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. AB - The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson's disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS. PMID- 24231558 TI - Contralateral hearing loss after acoustic neuroma surgery. AB - A 74-year-old man suffered contralateral hearing loss after left acoustic neuroma surgery. Steroid therapy was administered, but no improvement was observed. Contralateral hearing loss is an extremely rare and distressing complication that can occur following acoustic neuroma surgery. Although the mechanism of this rare phenomenon remains unclear, we speculate that in this patient the loss of cerebrospinal fluid or internal auditory artery thrombosis may be involved. PMID- 24231559 TI - Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. AB - This meta-analysis aimed to systematically collect and synthesize the current evidence regarding the efficacy and tolerability of levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types. We selected randomized-controlled trials (RCT) of LEV as an adjunctive therapy in epilepsy according to predefined criteria. Outcome measures included a > or =50% reduction in seizure frequency, seizure freedom, and adverse events. Thirteen RCT were analyzed. Results showed that the efficacy of adjunctive LEV was superior to placebo both in achieving > or =50% reduction in seizure frequency (pooled odds ratio [OR] 3.36, 95% confidence interval [CI] 2.78-4.07, Z=12.46; p<0.00001) and seizure freedom (pooled OR 4.72, 95% CI 2.96-7.54, Z=6.50; p<0.00001). The heterogeneity was mild (chi-squared=12.28, I2=2% in > or =50% reduction in seizure frequency, and chi squared=0.49, I2=0% in seizure freedom). Subgroup analysis suggested similar effects across different dosages in adults. The incidence of adverse reactions was not significantly different between the LEV group and the placebo group. The adverse events of relatively high incidence in the LEV group included somnolence, agitation, dizziness, asthenia, and infection. Incidence of serious adverse reaction such as rash and white blood cells and platelets decreasing was quite low. Adjunctive therapy with LEV was superior to placebo in reducing the frequency of seizures in patients with partial and idiopathic generalized epilepsy with effect in both adults and children, and demonstrated good tolerance in patients with epilepsy. PMID- 24231560 TI - High dose versus low dose steroids in children with tuberculous meningitis. AB - Guidelines for the best steroid dose in children with tuberculous meningitis (TBM) have not been established. We enrolled 63 children with TBM and divided them into three steroid dose groups: Group 1 (prednisolone 2mg/kg/day over 4 weeks), Group 2 (prednisolone 4 mg/kg/day over 1 week and 2mg/kg/day for the next 3 weeks) and Group 3 (prednisolone 4 mg/kg/day over 4 weeks). All patients received standard antituberculous therapy. Optic atrophy, tuberculoma, hydrocephalus, mental retardation, spasticity, hearing impairment, vasculitis and mortality outcomes were compared. Optic atrophy was higher in Group 3 compared to Group 1 (odds ratio [OR]=2.8) and Group 2 (OR=2.8), although Group 3 had a high incidence of optic atrophy at diagnosis. Tuberculomas were more frequent in Group 1 (OR=2.4) and Group 3 (OR=3.0) as compared to Group 2. Infarcts were more common in Group 3 than in Group 1 (OR=1.9) and in Group 2 (OR=3.5). Hearing loss was higher in Group 2 as compared to Group 1 (OR=2.88) and Group 3 (OR=4.8). Evolving hydrocephalus was higher in Group 3 as compared to Group 2 (OR=2.8) and Group 1 (OR=3.1). Mental retardation was higher in children in Group 3 (OR=1.6) and in Group 2 (OR=1.9) as compared to Group 1. Spasticity was higher in Group 3 (OR=2.0) and in Group 2 (OR=1.4) as compared to Group 1. There was no difference in mortality between the groups. We conclude that prednisolone at a dose of 4 mg/kg/day for 1 week followed by 2mg/kg/day for 3 weeks is associated with fewer tuberculomas and infarcts but a higher incidence of hearing loss. A prolonged period of high dose steroids increases the risk of optic atrophy and hydrocephalus. Prednisolone at a dose of 2mg/kg/day is associated with lower risk of mental retardation and spasticity. PMID- 24231561 TI - From above or below: the controversy and historical evolution of tuberculum sellae meningioma resection from open to endoscopic skull base approaches. AB - In the early 20th century, the first successful surgical removal of a tuberculum sellae meningioma (TSM) was performed and described by Harvey Cushing. It soon became recognized that TSM pose a formidable challenge for skull base surgeons because of their deep and sensitive location, proximity to critical neurovascular elements, and often dense and fibrous nature. Because of this, over the next several decades controversy transpired regarding their optimal method of resection. Early attempts involved utilization of open transcranial routes. This included classic bilateral and unilateral frontal approaches, followed by pterional or frontotemporal approaches, which have evolved to incorporate skull base modifications, such as the supraorbital, orbitozygomatic, and orbitopterional approaches. Minimally invasive supraorbital keyhole approaches through eyebrow incisions have also been adopted. Over the past 25 years, the microsurgical transsphenoidal approach, classically used for pituitary and parasellar tumors, was modified to resect suprasesllar TSM via the extended transsphenoidal approach. More recently, with the evolution of endoscopic techniques, resection of TSM has been achieved using purely endoscopic endonasal transplanum transtuberculum approaches. Although each of these techniques has been successfully described for the treatment of TSM, the question still remains: is it better to access and operate on these lesions via a traditional, transcranial avenue, or are they better treated via endoscopic endonasal techniques? We outline the surgical management of TSM through history, from early transcranial and transsphenoidal approaches to modern extended endoscopic endonasal procedures. We briefly explore the arguments favoring each of the methods and the advancements which have emerged to further optimize surgical resection. PMID- 24231562 TI - Hemangiopericytoma: Radical resection remains the cornerstone of therapy. AB - Hemangiopericytomas (HPC) are mesenchymal tumors with a propensity towards chronicity and metastasis. This study aimed to reflect a single institution experience with both World Health Organization (WHO) grade II and III HPC. Pathology records from the years 1990-2013 at the University of Washington were searched to identify tumors unequivocally classified as HPC. Electronic chart review was then utilized to collect pertinent patient data. Of the WHO grade II HPC, there were four men and two women (average age 52 years) while the grade III HPC group had eight men and two women (average age 51 years). Sixty-six percent of WHO grade II tumors were located in the middle or posterior fossa as compared to none of the grade III tumors. Survival analysis revealed a significant survival benefit for patients who underwent complete resection (223 months) versus those with subtotal resection (138 months, p<0.05). Factors such as age, sex, the use of up-front radiation, and whether the patient had a recurrence did not show statistical significance related to overall survival or progression free survival. Radiation in the form of external beam radiotherapy given at the time of the first recurrence did trend towards improved progression free survival (56 months) compared to those patients who were not radiated (22 months, p=0.09) All patients with radical resection went on to never have a recurrence. Our results indicate that HPC are tumors with limited response to radiation and best treated with aggressive resection. Future studies will determine whether molecular-based therapies may provide added adjuvant benefit. PMID- 24231563 TI - Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI. AB - When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p=0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p=0.004) and incomplete visual acuity recovery (<=6/12) after 1 year (p=0.002). Lower conversion rates were found in patients with optic disc edema (p=0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate. PMID- 24231564 TI - Association between CRP gene polymorphism 717A/G, C-reactive protein and neurological deficit in ischemic stroke. AB - Inflammatory components play an important role in the pathogenesis of arteriosclerosis, one of the main causes of stroke. Blood C-reactive protein (CRP) level is connected with the severity of neurological deficit and disability after stroke. Production of CRP depends on CRP gene polymorphism. This study enrolled 125 patients with ischemic stroke. CRP 717A/G polymorphism was tested in all patients along with an assay of CRP levels measured on the first and tenth day after stroke onset. Neurological deficit on admission and before discharge from hospital was evaluated according to National Institutes of Health Stroke Scale (NIHSS), and then associated with CRP levels and the CRP polymorphism. The CRP 717AA genotype was the most frequent, observed in 53.6% of patients; AG genotype in 40%, and GG genotype in 6.4%. Carriers of the 717GG genotype had a significantly higher CRP level on the first day after stroke versus heterozygotes (p=0.023). The improvement in neurological state evaluated with the NIHSS was significantly better in CRP 717AA patients in comparison with other CRP 717 genotypes (p=0.035). A higher level of CRP on the first day after ischemic stroke was slightly associated with the CRP 717AG genotype. The CRP 717AA genotype promotes improvement of neurological state in patients with ischemic stroke. PMID- 24231565 TI - Finding the missing link in neuromyelitis optica presenting with recurrent transverse myelitis flares. AB - Neuromyelitis optica (NMO) is a distinct clinical entity from multiple sclerosis with its own clinical, laboratory and pathological characteristics. Definitive diagnosis of NMO is challenging at times as there can be a long interval between the occurrence of the index event and other neurological deficits which would fulfill the diagnostic criteria. Detection of NMO antibody could serve as an early marker in the disease progression. We present a young woman previously identified to have NMO antibody with recurring episodes of transverse myelitis for 3 years before manifesting with optic neuritis. PMID- 24231566 TI - An audit of immunohistochemical marker patterns in meningioma. AB - Meningiomas may express a number of potentially growth-promoting receptors including receptors for progesterone, growth hormone and vascular endothelial growth factor (VEGF). These and other receptors are potential targets for chemotherapy. We have prospectively studied a panel of markers as a routine in order to obtain data of individual expression of markers that may provide targets for anti-receptor treatment. One hundred and seventy-five consecutive patients operated on for meningiomas between 2005 and 2008 were prospectively analysed with antibodies against receptors for growth hormone, insulin-like growth factor 1 (IGF-1), androgen receptors, progesterone receptors (PR) and antibodies against CD34, VEGF, Ki-67 and caspase-3. Expression of IGF-1 receptor (IGF-1r), epidermal growth factor receptor (EGFR) E30 and growth hormone receptor (GHr) was conserved across histological grades and found in 88% to 94% of meningiomas. PR were detected in 87%, but expression decreased in aggressive tumours. Angio-markers such as VEGF and CD34 were detected in 69% and 17% of meningiomas, respectively. Androgen receptors and caspase-3 were uncommon. The analyses of a panel were undertaken as a clinical routine in order to assess its feasibility and to provide data that can be utilised in a clinical setting. Three putative therapeutic receptor targets, IGF-1r, GHr and EGFR E30 were expressed in a large majority of tumours and in contrast to PR maintained expression despite increasing pathological grade of meningioma. Our data also suggest that anti progesterone therapies and anti-angiogenic therapies could be targeted to subsets of meningioma patients who express PR or have CD34-positive tumours. PMID- 24231567 TI - Patterns of organ donation among resuscitated patients at a regional cardiac arrest center. AB - INTRODUCTION: As organ demand outpaces supply in the United States, donation after cardiac death (DCD) is increasing, and the leading cause of death among donors is now cardiovascular/cerebrovascular disease. Selected patients resuscitated from cardiac arrest may be an under-recognized donor pool. Regional cardiac arrest centers are expected to address organ donation, but there are few guidelines available and the yield from this population is not fully known. METHODS: We characterized the progression of resuscitated cardiac arrest patients at a regional cardiac arrest center and transplant center from organ procurement organization (OPO) referral through procurement. We determined characteristics associated with donation, assessed temporal trends in referral and donation, and calculated the yield of organs from this cohort. RESULTS: Of 991 patients admitted between 2005 and 2011, 560 did not survive to hospital discharge. Of these, 530 (94.6%) were referred to the OPO and 75 (13.4%) had organs procured. Family refusal of otherwise suitable candidates precluded 71 procurements. Age, sex, arrest location, designated donor status, and family consent were associated with donation. The absolute number of admissions, referrals, and donors increased over the study period. The probability of OPO referral did not change, but the probability of donation increased. The overall yield was 1.8 solid organs and 1.3 eyes per donor, with the majority being transplanted. CONCLUSIONS: Post-cardiac arrest patients represent a potential donor pool to help fill the widening gap between organ supply and demand in the United States. Formal multi-modal neurologic assessment may expedite referral to an organ procurement organization. These components should be considered as cardiac arrest center designation criteria. PMID- 24231568 TI - Quality of evidence in studies evaluating neuroimaging for neurologic prognostication in adult patients resuscitated from cardiac arrest. AB - AIM: Neuroimaging has been proposed as a predictor of neurologic outcome in comatose survivors of cardiac arrest. We reviewed the quality and level of evidence of the current neuroimaging literature for predicting neurologic outcome in cardiac arrest patients treated with or without therapeutic hypothermia (TH). DATA SOURCES: Medline, EMBASE, and Cochrane Databases were searched using the terms "cardiac arrest," "cardiopulmonary resuscitation," "brain hypoxia," "brain anoxia," "brain hypoxia-ischaemia," "neuroimaging," and "prognosis." Eligible studies were reviewed and classified by level of evidence and methodological quality as defined by the International Liaison Committee on Resuscitation (ILCOR). RESULTS: 928 studies were identified, 84 of which met inclusion criteria: 74 were supportive of neuroimaging to predict outcome, eight unsupportive, and two equivocal. Several studies investigated more than one imaging modality: 27 investigated computed tomography (CT), 46 magnetic resonance imaging (MRI), and 18 alternate imaging modalities, including positron emission tomography and single photon emission computed tomography. No randomized controlled trials were identified. Seven cohort and case control studies were identified, only one of which was graded "good" quality, two were "fair" and four were "poor." CONCLUSION: Neuroimaging is an evolving modality as a prognostic parameter in cardiac arrest survivors. However, the quality of the available literature is not robust, highlighting the need for higher quality studies before neuroimaging can be supported as a standard tool for prognostication in the patient population. PMID- 24231569 TI - Awakening after cardiac arrest and post resuscitation hypothermia: are we pulling the plug too early? AB - BACKGROUND: Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37 degrees C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening. METHODS: With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006-2010. They were treated with TH (target of 33 degrees C) for 24h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range. RESULTS: The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37 degrees C and regaining consciousness. The 69 patients that regained consciousness in <=48h after rewarming were termed "early awakeners". Ten patients regained consciousness 48-72h after rewarming and were termed "intermediate-awakeners". Ten patients remained comatose and apneic >72h after rewarming but eventually regained consciousness; they were termed "late awakeners". The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0-47), 60.5 [56,64.5] (range 49-71), and 126 [104,151]h (range 73-259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners. CONCLUSION: Following OHCA and TH, arbitrary withdrawal of life support <48h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48h after rewarming. PMID- 24231570 TI - Cerebrospinal fluid biomarkers in cardiac arrest survivors. AB - AIM: The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid beta (Abeta) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA). METHODS: CSF levels of neurofilament light protein (NFL), total tau (T-tau), hyperphosphorylated tau (P-tau), YKL-40, Abeta38, Abeta40, Abeta42, soluble amyloid precursor protein alpha and beta (sAPPalpha and sAPPbeta) were measured in 21 patients approximately two weeks after CA and in 21 age-matched neurologically healthy controls. The biomarker levels were also compared between patients with good and poor long-term clinical outcome according to Glasgow Outcome Scale (GOS), activities of daily living (ADL) and mini-mental state examination (MMSE), measuring neurologic function, daily functioning and cognitive function, respectively. RESULTS: Patients with CA had a very marked increase in the CSF levels of NFL, T-tau and YKL-40 as compared with controls. The levels were increased at about 1200, 700 and 100%, respectively. NFL and T tau were significantly higher in patients with poor outcome according to all three outcome measures. Patients with poor outcome according to GOS and ADL had higher levels of YKL-40. Levels of Abeta38, Abeta40, Abeta42, sAPPalpha and sAPPbeta were lower in patients with a low MMSE score. P-tau was not significantly altered. CONCLUSIONS: Biomarkers reflecting neuronal damage and inflammation, but not so much Abeta metabolism, were significantly altered in patients after a CA, and the changes were more pronounced in the groups with poor outcome. This calls for future larger studies to determine the prognostic potential of these biomarkers. PMID- 24231571 TI - The association of body mass index with time to target temperature and outcomes following post-arrest targeted temperature management. AB - BACKGROUND: Evidence suggests that more rapid attainment of target temperature (32-34 degrees C) improves neurologic outcome following cardiac arrest and targeted temperature management (TTM). It is unclear to what extent body mass index (BMI) is associated with the time to reach target temperature and subsequent clinical outcomes. OBJECTIVE: We sought to determine whether the time to target temperature was affected by BMI. In addition, we wished to determine whether the incidence of skin breakdown, survival to discharge and neurologic outcomes were associated with BMI. METHODS: Multicenter retrospective cohort study of cardiac arrest patients who underwent TTM between July 2007 and December 2012. We examined the association between BMI and the time from initiation of cooling to attainment of target temperature (32-34 degrees C). RESULTS: Of 236 patients treated with TTM, 184 were included in the study. Mean age was 57.8+/ 17.0 years; 78/184 (42%) were female and 48/184 (26%) had VF/VT as the initial rhythm. Median time to reach target temperature from ROSC was 6.4 (4.1, 9.8)h and median time from initiation of TTM to target temperature was 3.4 (2.1, 5.8)h. Cooling duration was a median of 24.0 (23.0, 24.0)h and median rewarming time was 12.0 (9.5, 18.0)h. Overall, 104/184 (56.5%) achieved target temperature within 4h and 128/184 (69.6%) within 6h. Increased BMI was associated with a longer time to achieve target temperature from initiation of TTM (p=0.01). There was no significant difference across BMI groups in time to achieve target temperature from ROSC (0.07), skin breakdown (p=0.35), survival (p=0.21), nor rate of good neurologic outcome (p=0.32). CONCLUSIONS: Target temperature was frequently achieved within 4-6h; as BMI increased, the time to reach target temperature from initiation of TTM was prolonged. There was no significant difference across BMI groups for survival or good neurologic outcome. PMID- 24231573 TI - Annals of Plastic Surgery Adopts and Recommends the SAMPL Guidelines for Statistical Analyses. PMID- 24231572 TI - A novel heterozygous mutation in steroidogenic factor-1 in pubertal virilization of a 46,XY female adolescent. AB - BACKGROUND: Steroidogenic factor-1 (SF-1) gene (NR5A1) mutations cause disorders of sexual development due to gonadal dysgenesis, particularly in 46,XY individuals. In cases exhibiting this mutation, the phenotype is heterogeneous, and it may vary within a spectrum ranging from complete female appearance to an infertile male. Virilization observed in some cases in the pubertal age group may lead to diagnostic difficulties. CASE: The present case report describes the clinical, histopathologic, and genetic characteristics of a 46,XY case, who was born with a female phenotype and raised as a girl, presented with findings of virilization in the pubertal period. She had no germ cells and very few Leydig cells with atrophic testis on biopsy and in whom a novel heterozygous mutation in the SF-1 gene (a heterozygous 7-bp deletion mutation in exon 7 [c.1308 1314del7bp] causing frameshift) was identified. SUMMARY AND CONCLUSION: Although the gonads are very dysgentic in patient with SF-1 mutations, sufficient androgen synthesis can cause severe virilization during puberty. PMID- 24231574 TI - Amniotic fluid for ex vivo skin preservation: a comparative study of tissue preservation solutions. AB - Ex vivo skin preservation is important for skin banks, burn centers, and in research; however, the optimal preservation solution is not known. Human amniotic fluid (HAF), in addition to its role in fetal wound healing, has promise as an effective and readily available preservation solution. The purpose of this study was to compare the efficacy of several solutions, including HAF, in full thickness skin preservation. Human amniotic fluid was obtained from patients undergoing amniocentesis. Full-thickness skin obtained during abdominoplasty was divided into 1-cm(2) samples. These specimens were preserved in either saline, HAF from a single patient, pooled HAF, University of Wisconsin solution, or custodial histidine-tryptophan-ketoglutarate solution at 4 degrees C. There were 5 samples in each group. Specimens were examined for keratinocyte survival at 7, 14, 21, 28, and 35 days using the trypan blue assay. The first 200 cells identified were counted to calculate the degree of cell death. Comparisons were made between the groups, and a multivariable repeated-measures analysis was performed to determine statistical significance, which was defined as P < 0.05. The individual and pooled HAF showed greater keratinocyte survival than the other solutions, at each time point. The difference was statistically significant (P < 0.05) when compared to saline and custodial solution but not statistically significant when compared to University of Wisconsin solution. When used as a tissue preservation solution, HAF produces superior keratinocyte survival than several commercially available solutions. Amniotic fluid, nature's tissue preservation solution, may be an inexpensive, readily available alternative for use in skin banks, burn centers, and research. PMID- 24231575 TI - Comparison of hatchet-shaped tensor fascia lata flap and pedicle anterior lateral thigh flap for treatment of trochanteric sores: a retrospective analysis of 48 patients. AB - PURPOSE: Surgical reconstruction of trochanteric sores remains a formidable task for plastic surgeons. Diverse types of flaps have been proposed for use in this situation, each with particular advantages and limitations. This study aimed to compare the surgical outcomes between the hatchet-shaped tensor fascia lata (TFL) flap and the pedicle anterior lateral thigh (ALT) flap in treatment of trochanteric sores. METHODS: Forty-eight patients with trochanteric sores were operated on under spinal or general anesthesia using TFL or ALT flaps between August 2007 and November 2010. In the TFL group, 26 hatchet-shaped TFL musculocutaneous flaps were performed on 24 patients. In the ALT group, 25 pedicle ALT musculocutaneous flaps were performed on 24 patients. Surgical outcomes were retrospectively analyzed. RESULTS: No significant difference was detected between the TFL and ALT groups in terms of age, preoperative disease period, obesity (body mass index), American Society of Anesthesiologists score, comorbidity, the defect size, follow-up time, and complication rate. The recurrence rate and the flap size were significantly higher in the TFL group than in the ALT group (P = 0.022; P < 0.001). The operation time was longer in the ALT group (P < 0.001). CONCLUSIONS: The pedicle ALT flap is a more effective treatment than the TFL flap for the surgical management of trochanteric sores. The hatchet-shaped TFL flap should be reserved for the reconstruction of recurrent trochanteric sores or for use in the critically ill patient who cannot tolerate longer anesthesia and operation time. PMID- 24231576 TI - A new vascularized cervical lymph node transplantation model: an anatomic study in rats. AB - INTRODUCTION: Vascularized lymph node transfer is of high interest for the treatment of lymphedema. Currently, there are few experimental small animal models of vascularized lymph node transplantation. In this article, our aim was to describe a new vascularized cervical lymph node transplantation model in rats. MATERIALS AND METHODS: Ten male Sprague-Dawley rats weighing 200 to 250 g were used in this study. The anatomic features of the neck lymph nodes in rats were explored. Anatomic neck dissections were performed, and lymph node flaps were harvested. The common carotid artery and the jugular vein were used as the vascular pedicles of the lymph node flap. Methylene blue dye was injected into the arterial pedicle. Lymph nodes were identified, and their structure was confirmed by histological evaluation. Laser-assisted indocyanine green angiography was used to confirm perfusion of the lymph node flap. RESULTS: An adequate perfusion was observed in the lymph node flap. The dye disseminated evenly within the lymph nodes, indicating that the flap had a well-established vascular network and an adequate blood supply. Macroscopically, perfusion of 5 to 6 lymph nodes was observed. Histological examination of tissue samples confirmed well-defined lymph nodes. After indocyanine green administration, fluorescence was observed throughout the lymph node flap and within the venous pedicle of the flap. CONCLUSIONS: To the best of our knowledge, this is the first report describing vascularized lymph node flap in the head and neck region of a rat. Our lymph node flap preparation technique confirmed the presence of 5 to 6 lymph nodes within the flap. The presented vascularized lymph node flap can be applied to transplantation studies, lymphedema studies, and to studies on immunological mechanism of tolerance and rejection. PMID- 24231577 TI - Modelling and engineering of stress based controlled oxidation effects for silicon nanostructure patterning. AB - Silicon nanostructure patterning with tight geometry control is an important challenge at the bottom level. In that context, stress based controlled oxidation appears to be an efficient tool for precise nanofabrication. Here, we investigate the stress-retarded oxidation phenomenon in various silicon nanostructures (nanobeams, nanorings and nanowires) at both the experimental and the theoretical levels. Different silicon nanostructures have been fabricated by a top-down approach. Complex dependence of the stress build-up on the nano-object's dimension, shape and size has been demonstrated experimentally and physically explained by modelling. For the oxidation of a two-dimensional nanostructure (nanobeam), relative independence to size effects has been observed. On the other hand, radial stress increase with geometry downscaling of a one-dimensional nanostructure (nanowire) has been carefully emphasized. The study of shape engineering by retarded oxidation effects for vertical silicon nanowires is finally discussed. PMID- 24231578 TI - Scale model on performance prediction in recreational and elite endurance runners. AB - PURPOSE: To identify the effect of allometric scaling on the relationship between running efficiency (R(Eff)) and middle-distance-running performance according to performance level. METHODS: Thirteen male recreational middle-distance runners (mean +/- SD age 33.3 +/- 8.4 y, body mass 76.4 +/- 8.6 kg, maximal oxygen uptake [VO(2max)] 52.8 +/- 4.6 mL . kg(-1) . min(-1); G1) and 13 male high-level middle distance runners (age 25.5 +/- 4.2 y, body mass 62.8 +/- 2.7 kg, VO(2max) 70.4 +/ 1.9 mL . kg(-1) . min(-1); G2) performed a continuous incremental test to volitional exhaustion to determine VO(2max) and a 6-min submaximal running test at 70% of VO(2max) to assess R(Eff). RESULTS: Significant correlation between R(Eff) and performance were found for both groups; however, the strongest correlations were observed in recreational runners, especially when using the allometric exponent (respectively for G1, nonallometric vs allometric scaling: r = .80 vs r = .86; and for G2, nonallometric vs allometric scaling: r = .55 vs r = .50). CONCLUSION: These results indicate that an allometric normalization may improve endurance-performance prediction from R(Eff) values in recreational, but not in elite, runners. PMID- 24231580 TI - Short versus long cephalomedullary nails for the treatment of intertrochanteric hip fractures in patients older than 65 years. AB - OBJECTIVES: To compare failure rates between short and long cephalomedullary nails used for the treatment of intertrochanteric hip fractures in patients over 65 years of age. DESIGN: Retrospective cohort study. Data were collected from medical records and radiographs. SETTING: Three level 1 trauma centers. PATIENTS/PARTICIPANTS: Patients aged 65 years or older who underwent treatment of an intertrochanteric hip fracture with a cephalomedullary nail between January 2004 and December 2010. INTERVENTION: Open reduction and internal fixation of intertrochanteric hip fracture with either short or long cephalomedullary nail. MAIN OUTCOME MEASUREMENT: Postoperative treatment failure rate, defined as periprosthetic fracture or reoperation requiring removal or revision of nail, including conversion to arthroplasty. RESULTS: Incidence of treatment failure (periprosthetic fracture and reoperation requiring removal of nail) was 30 of 559 (5.4%) for the entire cohort; 13 of 219 (5.9%) occurred after placement of a short nail compared with 17 of 340 (5.0%) after placement of a long nail (P = 0.70). There were 11 of 559 (2.0%) patients who sustained a periprosthetic fracture after nailing, 6 of 219 (2.7%) after short nails and 5 of 340 (1.5%) after long nails (P = 0.35). The remaining 19 treatment failures were major reoperations requiring removal of nail, 7 of 219 (3.2%) after short nails and 12 of 340 (3.5%) after long nails (P = 0.81). The reasons for these 19 revision procedures were: screw/helical blade cutout (16), progressive arthritis with conversion to arthroplasty (1), avascular necrosis of femoral head with conversion to arthroplasty (1), and symptomatic leg length discrepancy with conversion to arthroplasty (1). Median follow-up period for patients living at least 1 year postoperatively was 30 months (range, 12-85 months). Overall, 175 of 698 (25%) patients died within 1 year after index surgery. CONCLUSIONS: When using contemporary cephalomedullary implants, short and long nails exhibit similar treatment failure rates. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 24231584 TI - Shorter telomere length is linked to brain atrophy and white matter hyperintensities. AB - BACKGROUND: leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging. METHODS: we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years. RESULTS: shorter TL was related to greater degree of subcortical atrophy (beta = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs. CONCLUSION: this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain. PMID- 24231583 TI - Dynamic fixation of distal femur fractures using far cortical locking screws: a prospective observational study. AB - OBJECTIVES: Document fixation and healing of distal femur fractures stabilized by plate osteosynthesis using far cortical locking (FCL) screws. DESIGN: Prospective and observational. SETTING: Two level 1 and 1 level 2 trauma centers. PATIENTS: Thirty-two consecutive patients with 33 distal femur fractures (AO/OTA types 33A, 33C). INTERVENTION: Fractures were stabilized by plate osteosynthesis with MotionLoc FCL screws without supplemental bone graft or bone morphogenic proteins. Patients were followed up for a minimum of 1 year with functional and radiographic assessments obtained at postoperative weeks 6, 12, and 24 and computed tomography scans at week 12. If union was not confirmed within 1 year, follow-up was continued until union or revision surgery. MAIN OUTCOME MEASURES: The primary end point was fracture union in the absence of complications and secondary interventions. Fracture healing was defined by resolution of pain at the fracture site and cortical bridging on biplanar radiographs. Complications were defined by fixation failure, loss of reduction, implant breakage, infection, nonunion, and need for revision. RESULTS: Thirty-one fractures were available for follow-up. None of the 125 FCL screws used for diaphyseal fixation broke or lost fixation. One of the 31 fractures displaced into varus (DeltaVarus = 5.8 degrees). Thirty of the 31 fractures healed within 15.6 +/- 6.2 weeks. At an average follow-up of 17 +/- 4 months, there were 2 revisions: one to correct a malrotation at day 5 and one to treat a nonunion at 6 months. CONCLUSIONS: Absence of implant and fixation failure suggests that dynamic plating of distal femur fractures with FCL screws provides safe and effective fixation. PMID- 24231585 TI - Epidemiology of lifetime fracture prevalence in England: a population study of adults aged 55 years and over. AB - BACKGROUND: fractures remain a substantial public health problem but epidemiological studies using survey data are sparse. This study explores the association between lifetime fracture prevalence and socio-demographic factors, health behaviours and health conditions. METHODS: fracture prevalence was calculated using a combined dataset of annual, nationally representative health surveys in England (2002-07) containing 24,725 adults aged 55 years and over. Odds of reporting any fracture was estimated separately for each gender using logistic regression. RESULTS: fracture prevalence was higher in men than women (49 and 40%, respectively). In men, factors having a significant independent association with fracture included being a former regular smoker [odds ratios, OR: 1.18 (1.06-1.31)], having a limiting long-standing illness [OR: 1.47 (1.31 1.66)] and consuming >8 units of alcohol on the heaviest drinking day in the past week [OR: 1.65 (1.37-1.98)]. In women, significant factors included being separated/divorced [OR: 1.30 (1.10-1.55)], having a 12-item General Health Questionnaire (GHQ-12) score of 4+ [OR: 1.59 (1.27-2.00)], consuming >6 units of alcohol in the past week [OR: 2.07 (1.28-3.35)] and being obese [OR: 1.25 (1.03 1.51)]. CONCLUSION: a range of socio-demographic, health behaviour and health conditions, known to increase the risk of chronic disease and premature death, are also associated with fracture occurrence, probably involving the aetiological pathways of poor bone health and fall-related trauma. PMID- 24231586 TI - Proprioception: where are we now? A commentary on clinical assessment, changes across the life course, functional implications and future interventions. AB - Proprioception, the sense of where one is in space, is essential for effective interaction with the environment. A lack of or reduction in proprioceptive acuity has been directly correlated with falls and with reduced functional independence in older people. Proprioceptive losses have also been shown to negatively correlate with functional recovery post stroke and play a significant role in other conditions such as Parkinson's disease. However, despite its central importance to many geriatric syndromes, the clinical assessment of proprioception has remained remarkably static. We look at approaches to the clinical assessment of proprioception, changes in proprioception across the life course, functional implications of proprioception in health and disease and the potential for targeted interventions in the future such as joint taping, and proprioception specific rehabilitation and footwear. PMID- 24231587 TI - Isolated tuberculous liver abscess in an immunocompetent adult patient: A case report and literature review. AB - Tuberculous liver abscess is a rare disease entity even in endemic areas of Mycobacterium tuberculosis. It is usually accompanied by pulmonary tuberculosis or enteric tuberculosis. Further, an isolated tuberculous liver abscess is extremely rare. The disease is diagnosed by laparotomy or postmortem autopsy in most cases, and some authors adopted a 9-month antituberculosis regimen. We herein report a case of an isolated tuberculous liver abscess that initially manifested as persistent fever and general malaise, which was diagnosed by liver biopsy and treated successfully with a 6-month antituberculosis regimen and percutaneous abscess drainage. PMID- 24231588 TI - Bacillus Calmette-Guerin is a preventive factor in mortality of childhood tuberculous meningitis. AB - OBJECTIVES: Studies have been done that have focused on the efficacy of bacillus Calmette-Guerin (BCG) vaccination in the prevention of cases of childhood tuberculous meningitis (TBM). However the efficacy of the vaccination in the prevention of mortality has not been sufficiently evaluated. This study aimed to determine the main features of TBM cases in childhood and to evaluate the factors related to mortality, proving the protective effect of BCG vaccination in childhood TBM. METHODS: In a retrospective approach, all consecutive cases of TBM in children that occurred between 1997 and 2005, at Dicle University Hospital, were studied. The following data were evaluated: demographic aspects, admission symptoms, radiology and laboratory findings, BCG vaccination status, tuberculin skin test (TST) positivity, and mortality rates. RESULTS: In total, 172 cases of childhood TBM were evaluated (mean age 53.3+/-55.7 months; 109 boys (63.4%)). The majority of these cases (70.4%) had typical TBM symptoms on admission. BCG vaccination data were available for 152 (88.4%) cases and 29 of them (19.1%) were positive. The TST was performed for 143 patients (83.1%) and 28 (19.6%) were found positive. Hydrocephalus was identified in 118 patients (68.6%) on computed tomography examination. A shunt was placed in 79 cases (45.9%). In total, 24 patients (14.0%) died in the hospital. TST negativity was a significant factor for mortality (p=0.012). BCG positivity was found to be a preventive factor from mortality (p=0.05). CONCLUSIONS: BCG vaccination is effective in the prevention of TBM-associated mortality in childhood. TST negativity may be a sign of a poor prognosis in TBM cases. PMID- 24231589 TI - [Infective endocarditis in two Spanish university hospitals in different geographical locations with and without a cardiac surgery department]. AB - OBJECTIVES: To assess possible differences in clinical presentation, microbiology, morbidity and mortality of infective endocarditis between two Spanish hospitals, one on the mainland that has cardiac surgery and one in the Canary Islands without this service. METHOD: A total of 229patients consecutively diagnosed of endocarditis between 2005 and 2012, including pediatric population, were studied in the Reina Sofia Hospital (Cordoba, n=119) and Nuestra Senora de Candelaria Hospital (Tenerife, n=110). We compared the clinical, microbiological and echocardiographic data and analyzed mortality differences by binary logistic regression analysis. RESULTS: There were no differences in underlying heart disease, proportion of surgery, or the microbiological profile. The proportion of infections attributable to catheter was higher in the Canary Islands hospital (13.6% vs 3.4%). Mortality was also higher (31.8% vs 18.5%, P=.020), although this difference was no longer significant in the multivariate analysis (OR=1.85; 95%CI, 0.70-4.87; P=.213). Age (OR=1.04/year; 95%CI, 1.01-1.07; P=.006), cardiac complications (OR=5.05; 95%CI, 1.78-14.34; P=.002), persistent sepsis (OR=4.89; 95%CI, 2.09-11.46; P<.001), and emergent surgery (OR=4.43, 95%CI, 1.75-11.19; P=.002) were independent predictors of death. Time to surgery, length of stay in the hospital without a surgical service (20 [13-30.5] vs 13 [6-25] days; P=.019) was not associated with outcome. CONCLUSIONS: There are differences in the presentation of endocarditis between two distant hospitals in Spain. The different hospital mortality can not be directly related to the presence of a surgery service. PMID- 24231590 TI - [Influence of Pneumonia Severity Index in the decision-making process in the emergency department]. PMID- 24231591 TI - [Intermediate uveitis in an immunocompetent patient]. PMID- 24231592 TI - Indomethacin submicron particle capsules provide effective pain relief in patients with acute pain: a phase 3 study. AB - Although frequently prescribed to relieve acute pain in patients, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with dose-related gastrointestinal, cardiovascular, and renal complications. Investigational, submicron particle NSAIDs are being developed that could provide effective pain relief at lower doses than currently available oral NSAIDs. This is the first phase 3 study evaluating the analgesic efficacy and safety of lower-dose indomethacin submicron particle capsules in patients following elective surgery. This multicenter, double-blind study enrolled patients aged 18 to 68 years who underwent bunionectomy under regional anesthesia. Patients with a pain intensity rating of >=40 mm on a 100-mm Visual Analog Scale were randomized to receive indomethacin submicron particle capsules (40 mg 3 times daily [TID], 40 mg twice daily [BID], or 20 mg TID), celecoxib (400 mg loading dose, then 200 mg BID), or placebo. The primary efficacy parameter was the overall (summed) pain intensity difference measured by a Visual Analog Scale during a period of 48 hours. Scheduled assessments measured secondary efficacy parameters such as patient pain intensity differences. Indomethacin submicron particle capsules 40 mg 3 times daily (509.6 +/- 91.9 overall [summed] pain intensity difference), 40 mg twice daily (328.0 +/- 92.9 overall [summed] pain intensity difference), and 20 mg 3 times daily (380.5 +/- 92.9 overall [summed] pain intensity difference) reduced pain intensity from 0 to 48 hours (P <= 0.046 for all 3 groups) compared with placebo (67.8 +/- 91.4 overall [summed] pain intensity difference). There was some evidence of patient analgesia for celecoxib (279.4 +/- 91.9 overall [summed] pain intensity difference; P = 0.103). Some evidence of pain control was observed in patients as early as 2 hours following administration of indomethacin submicron particle capsules and was sustained throughout the treatment period. Indomethacin submicron particle capsules were generally well tolerated by patients. These results suggest that lower-dose indomethacin submicron particle capsules are a potentially promising treatment option for patients with acute pain. PMID- 24231593 TI - Using viscosupplementation to treat knee osteoarthritis. AB - This article provides physicians specializing in nonsurgical sports medicine with an overview of viscosupplementation as a treatment for osteoarthritis (OA) pain. Osteoarthritis is a painful, disabling condition that is becoming more prevalent in patients and is generally treated using conservative nonpharmacologic measures. If conservative measures are unsuccessful at alleviating pain, current recommendations include prescribing acetaminophen and nonsteroidal anti inflammatory drugs to patients. However, long-term use of these agents increases the risk for liver, cardiovascular, gastrointestinal, and/or renal complications in patients. Viscosupplementation is the term used for intra-articular injection of hyaluronic acid/hylans. Intra-articular injections of these agents have good safety profiles and have shown efficacy for treating knee OA pain. Viscosupplementation injections relieve pain for <= 26 weeks, which is longer than the short-term pain relief derived from nonsteroidal anti-inflammatory drugs and corticosteroid injections. Additionally, viscosupplementation administered to patients in earlier stages of OA may be more beneficial than when given later in the treatment of OA. As part of a multimodal algorithm, viscosupplementation combined with conventional therapy or other pharmacologic agents has been shown to be more effective at managing OA than conventional care alone. This article reviews the evidence for using viscosupplementation as part of a comprehensive program for managing OA in patients. PMID- 24231594 TI - Intra- and interdisciplinary agreement in the rating of acromioclavicular joint dislocations. AB - BACKGROUND: Acromioclavicular (AC) joint dislocation is a common injury observed and treated by physicians from several disciplines; proper classification and communication of the diagnosis between physicians is essential to manage injuries properly. This study assessed inter- and intradepartmental agreement in the rating of AC joint dislocations and compared departments of orthopedic surgery, musculoskeletal (MSK) radiology, and emergency medicine (EM). METHODS: Fifty radiographs indicating a random distribution of AC dislocations (Rockwood types I, II, III, and V) were sent to 25 resident, fellow, and attending physicians; the study group consisted of orthopedic surgeons (n = 9), MSK radiologists (n = 7), and EM physicians (n = 9). Dislocations were rated by physicians using the Rockwood classification (excluding type IV) and rating agreement was derived using the multirater kappa statistic. RESULTS: Moderate rating agreement was found among orthopedic surgeons (kappa = 0.5147), which was higher than among radiologists (kappa = 0.3628) or EM physicians (kappa = 0.1894). Interdisciplinary rating agreement was highest between orthopedic surgeons and MSK radiologists and lowest between MSK radiologists and EM physicians. Attending orthopedic surgeons showed the highest rating agreement (kappa = 0.5167) compared with attending MSK radiologists (kappa = 0.3585) and attending EM physicians (kappa = 0.2612). In-training orthopedic surgeons had higher rating agreement (kappa = 0.4918) than in-training MSK radiologists (kappa = 0.4218) and in training EM physicians (kappa = 0.1410). DISCUSSION: Orthopedic surgeons exhibited the highest intradepartmental rating agreement in assessing AC joint injuries, but interdepartmental rating agreement was low. It is unclear if low interdepartmental rating agreement reflects classification or training weaknesses; recognition of these differences may help develop a more standardized education for physicians to improve the management of AC joint injuries. CONCLUSIONS: Interdisciplinary rating agreement of AC joint injuries is low. Further study may help improve education and communication about AC joint injuries among physicians. PMID- 24231595 TI - Operative and nonoperative treatment options for ACL tears in the adult patient: a conceptual review. AB - Injury to the anterior cruciate ligament (ACL) is common among athletic individuals. Both nonoperative and operative treatment options exist. The optimal treatment of an adult with an ACL tear depends on several patient-specific factors, including age, occupation, and desired activity level. In less active patients with sedentary jobs, nonoperative management, consisting of physical therapy, bracing, and activity modification can yield successful results. In active patients who want to resume participation in jumping, cutting, or pivoting sports, patients who have physically demanding occupations, or patients who fail a trial of nonoperative management, ACL reconstruction is recommended. Reconstruction utilizing autograft tissue is preferred over allograft, especially in the younger athlete, but allograft tissue is a reasonable option in the older (aged > 40 years) and less active adult, as well. Successful results have been achieved with both patellar tendon and hamstring grafts. The optimal treatment in adult patients with ACL tears should be based on careful consideration of the patient's goals for return to activity, knee-specific comorbidities, such as coexistent meniscal pathology or osteoarthritis, and his or her willingness to follow a detailed rehabilitation regimen. Our article provides an overview of current nonoperative and operative treatment options for adults with ACL tears, considers the outcomes of both nonoperative and operative strategies, and provides general recommendations as to the ideal management for a given patient. PMID- 24231596 TI - Complex cartilage cases in the athletic patient: advances in malalignment, instability, articular defects, and meniscal insufficiency. AB - For sports medicine specialists, patients presenting with multiple coexisting knee pathologies can be some of the most difficult to treat patients, especially those with cartilage pathology. In particular, articular cartilage lesions are often incidental findings, and the decision to treat patients must be based on the lesions' confirmed contribution to patient symptomatology. The combination of malalignment, ligamentous instability, and chondral/meniscal damage in patients is challenging to treat because of the difficulty in determining both the relative contribution of each of the pathologies to patient clinical condition and the timing of performing specific corrective procedures. Corrective operations performed in isolation to treat each of the pathologies have historically produced reasonable results in patients; however, combined procedures for treatment of combined pathologies may prove essential for the success of any single procedure. This review describes the clinical evaluation of patients with multiple coexisting knee pathologies and highlights current evidence-based treatment strategies for the management of these combined disorders. PMID- 24231597 TI - Continuous passive motion following cartilage surgery: does a common protocol exist? AB - Continuous passive motion (CPM) devices have the potential to improve the histological content as well as the rate and volume of chondrogenesis in repair tissue following chondral injury. However, clinical evidence is lacking to support broad implementation of CPM following cartilage restoration procedures. We searched PubMed, CINAHL, SPORTDiscus, and Cochrane for such terms as knee, continuous passive motion, CPM, ACI, ACT, autologous chondrocyte implantation, autologous chondrocyte transplantation, microfracture, marrow-stimulation technique, mosaicplasty, osteochondral autograft, and osteochondral allograft. Inclusion criteria were all English-language studies of human subjects, evidence levels I to IV, reporting the use of CPM following cartilage repair or restoration surgery in the knee. One hundred and seven studies met inclusion criteria. Sixty-three studies reported the use of CPM following autologous chondrocyte implantation; 28 reported the use of CPM following microfracture; 13 reported the use of CPM following osteochondral autograft; and 15 reported the use of CPM following osteochondral allograft (several studies reported > 1 type of cartilage procedure, which explains why the sum of all studies reporting a particular procedure [119] is greater than the number of studies included in the review [107]). Of the 5723 patients included, 60.8% were treated with autologous chondrocyte implantation, 23.1% were treated with microfracture, 6.4% were treated with osteochondral autograft, and 9.7% were treated with osteochondral allograft. Of the 6612 total defects, 5043 (76.3%) were tibiofemoral and 1569 (23.7%) were patellofemoral. Most reports of CPM use after cartilage restoration procedures did not include specific information on how it was implemented. Overall, the description of CPM protocols in published knee articular cartilage surgery studies was disappointing. The majority of studies did not describe common variables such as the duration of CPM therapy, the initiation of CPM therapy, and the initial range of motion used. The most commonly prescribed parameters within a CPM regimen are initiated on the first postoperative day, with an initial range-of-motion of 0 to 30 degrees and a frequency of 1 cycle per minute, and for 6 to 8 hours daily over 6 weeks. The lack of consistent standardized reporting of postoperative CPM protocols provides an impetus to researchers and clinicians to more clearly define and describe their use following knee articular surgery. PMID- 24231598 TI - Impact of diabetes mellitus on surgical outcomes in sports medicine. AB - Diabetes mellitus (DM) affects a significant proportion of the patients evaluated and treated by orthopedic surgeons who specialize in sports medicine. Sports medicine-related conditions associated with DM include tendinopathy, adhesive capsulitis of the shoulder, and articular cartilage disease. This article reviews the current literature adressing the effect of DM on surgical outcomes in sports medicine. In general, patients with DM undergo operations more frequently and experience inferior surgical outcomes compared with patients without DM. Diabetes mellitus is associated with increased rates of complications from sports medicine procedures, such as infection, delayed healing, and failure of the operation. However, additional research is needed to determine the full impact of DM on patient outcomes in sports medicine. Surgeons should be cognizant of special considerations in the population of patients with DM and aim to tailor the surgical management of this growing patient population. PMID- 24231599 TI - Patients with type 1 diabetes oxidize fat at a greater rate than age- and sex matched controls. AB - INTRODUCTION: Elevated patient blood glucose and exogenous insulin administration may affect substrate oxidation in patients with type 1 diabetes mellitus (T1DM); however, this has not been demonstrated with conviction. We examined substrate oxidation during incremental exercise in a group of subjects with T1DM and compared the results to those of an age- and sex-matched control group of subjects. METHODS: A group of subjects with T1DM (n = 29; 10 men, 19 women) was recruited for metabolic testing from a weeklong fitness camp. An age- and sex matched control group of subjects (n = 29; 10 men, 19 women) was recruited from the local community. Subjects were required to avoid strenuous exercise for 48 hours and fast for 2 hours prior to metabolic testing. An incremental test to exhaustion on either a stationary cycle or treadmill was administered to all subjects. Maximum oxygen consumption of subjects was measured (T1DM subjects: 41.4 +/- 1.9 mL/kg/min; control subjects: 48.4 +/- 1.3 mL/kg/min). Blood glucose was recorded at 20 and 5 minutes before the exercise test, and at 5 and 20 minutes after the exercise test. RESULTS: The T1DM and control subjects were matched for age, height, weight, and body composition. Subject blood glucose levels were higher in the group of subjects with T1DM than the control group at all times measured (P < 0.001). At all relative intensities of exercise (50%-80% maximum oxygen consumption; P < 0.050), absolute fat oxidation was higher in the group of subjects with T1DM (P < 0.050) and absolute carbohydrate oxidation was higher in the control group. CONCLUSION: Our data indicate that subjects with T1DM oxidize fat at a higher rate and carbohydrates at a lower rate when compared with age- and sex-matched controls at the same relative intensity of exercise, despite the elevated pre-exercise blood glucose of subjects with T1DM. PMID- 24231600 TI - Comparison of physical activity levels in physicians and medical students with the general adult population of the United States. AB - OBJECTIVE: Physicians who are physically fit have a higher likelihood of counseling their patients about physical activity. We sought to determine if the amount of physical activity in physicians and medical students differs from the general adult population of the United States and if geographic differences in physical activity levels exist. METHODS: A cross-sectional survey was distributed to physicians and medical students throughout the United States to determine their level of physical activity according to US Department of Health and Human Services (DHHS) 2008 guidelines; data were collected from participants from June 2009 through January 2010. Our data set was compared with physical activity data from the Centers for Disease Control and Prevention (CDC) and we used geographic regions defined by the US Census Bureau. RESULTS: Our survey respondents contained 631 attending physicians, 159 fellow physicians, 897 resident physicians, and 262 medical students. Only 64.5% of the general US adult population meets DHHS guidelines for physical activity, but 78% of the survey participants fulfilled the guidelines. The percentage of US adults who do not engage in leisure-time physical activity is 25.4% compared with 5.8% of survey participants. Survey respondents in the southern region had the lowest physical activity levels and participants in the western region had the highest levels. CONCLUSION: Physicians and medical students engage in more physical activity than the general US adult population. Regional differences in the general population's physical activity also persisted in physicians and medical students. Therefore, physicians who complete less physical activity may be less likely to encourage patients to engage in physical activity in geographic areas where the adult population is less active. PMID- 24231601 TI - Helpful or harmful? Potential effects of exercise on select inflammatory conditions. AB - Inflammation has been characterized as a double-edged sword, requiring a balance between health as maintained by regular exercise and activities that would exacerbate inflammatory diseases. The influence of exercise on inflammation is complex and has been widely studied in both healthy patient populations as well as populations of patients with many inflammatory and/or autoimmune rheumatic diseases. Inflammatory markers can be affected by the type of exercise and muscle contraction, as well as the intensity, duration, and consistency of the exercise sessions. Because of these potentially important effects, many members of the general public, as well as some clinicians, believe that exercise could exacerbate symptoms and accelerate the progression of such conditions. The effects of different types of exercise have been studied among patients with inflammatory conditions such as ankylosing spondylitis, systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, fibromyalgia, and idiopathic inflammatory myopathies, as well as congestive heart failure, type 2 diabetes mellitus, and metabolic syndrome, which are considered low-grade systemic inflammatory diseases. This review will help exercise professionals and clinicians understand the effects of exercise on inflammatory markers, as well as offer effective treatment options and recommendations for patients exercising with rheumatic or inflammatory conditions. PMID- 24231602 TI - Replication of elite music performance enhancement following alpha/theta neurofeedback and application to novice performance and improvisation with SMR benefits. AB - Alpha/theta (A/T) and sensory-motor rhythm (SMR) neurofeedback were compared in university instrumentalists who were novice singers with regard to prepared and improvised instrumental and vocal performance in three music domains: creativity/musicality, technique and communication/presentation. Only A/T training enhanced advanced playing seen in all three domains by expert assessors and validated by correlations with learning indices, strongest with Creativity/Musicality as shown by Egner and Gruzelier (2003). Here A/T gains extended to novice performance - prepared vocal, improvised vocal and instrumental - and were recognised by a lay audience who judged the prepared folk songs. SMR learning correlated positively with Technical Competence and Communication in novice performance, in keeping with SMR neurofeedback's known impact on lower-order processes such as attention, working memory and psychomotor skills. The importance of validation through learning indices was emphasised in the interpretation of neurofeedback outcome. PMID- 24231603 TI - Self-assembling of large ordered DNA arrays using superhydrophobic patterned surfaces. AB - In this paper we present a simple and robust method to realize highly ordered arrays of stretched and suspended DNA molecules over the millimeter length scale. To this end we used an ad hoc designed superhydrophobic surface made of high aspect-ratio silicon pillars, where we deposited a droplet containing genomic DNA. A precise positioning of DNA strands was achieved by shaping the silicon pillars so that sharpened features resembling tips were included. Such features allowed us to accurately control the droplet de-wetting dynamics, pinning DNA strands in a well-defined position above pillars. The proposed technique has the potential to positively impact on the development of novel DNA chips for genetic analysis. PMID- 24231604 TI - Comparison of measured and Monte Carlo simulated track structure parameters in nanometric volumes. AB - The track structure of ionising particles in biological matter can only be assessed by simulations, since neither the type of interaction and its products nor the interaction positions in biological matter can be detected with nanometer resolution. Hence, there is a need to benchmark the deployed computer codes using suitable experimental data. For this purpose, the frequency distributions of ionisation clusters produced in the sensitive volume of the PTB ion counting nanodosemeter by monoenergetic protons and alpha particles (with energies between 0.1 and 20 MeV) were measured. C3H8 and N2 were alternately used as the working gas. The measured data were compared with the results of simulations obtained with the PTB Monte Carlo code PTra. Measured and simulated characteristics of the particle track structure are in good agreement for protons over the entire energy range investigated. For alpha particles with energies above the Bragg peak a good agreement can also be seen, whereas for energies below the Bragg peak differences of as much as 25 % occur. PMID- 24231605 TI - Mobilizing peptides in immunity. PMID- 24231606 TI - Designing immunogenic peptides. AB - Peptides fulfill many roles in immunology, yet none are more important than their role as immunogenic epitopes driving the adaptive immune response, our ultimate bulwark against infectious disease. Peptide epitopes are mediated primarily by their interaction with major histocompatibility complexes (T-cell epitopes) and antibodies (B-cell epitopes). As pathogen genomes continue to be revealed, both experimental and computational epitope mapping are becoming crucial tools in vaccine discovery. Immunoinformatics offers many tools, techniques and approaches for in silico epitope characterization, which is capable of greatly accelerating epitope design. PMID- 24231615 TI - Immunology: Allergy's Achilles' heel? PMID- 24231616 TI - Antigenic peptides: Reviving nuclear translation. PMID- 24231617 TI - Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. AB - Cationic host defense (antimicrobial) peptides were originally studied for their direct antimicrobial activities. They have since been found to exhibit multifaceted immunomodulatory activities, including profound anti-infective and selective anti-inflammatory properties, as well as adjuvant and wound-healing activities in animal models. These biological properties suggest that host defense peptides, and synthetic derivatives thereof, possess clinical potential beyond the treatment of antibiotic-resistant infections. In this Review, we provide an overview of the biological activities of host defense and synthetic peptides, their mechanism(s) of action and new therapeutic applications and challenges that are associated with their clinical use. PMID- 24231618 TI - A peptide's perspective on antigen presentation to the immune system. AB - Specific immune responses are critically dependent on protein degradation products in the form of peptides. These peptides are presented by major histocompatibility complexes (MHCs), and recognition of MHC-peptide complexes by the immune system determines successful pathogen elimination, transplant rejection, autoimmunity or death. Here we review the immune response from the peptide's perspective and discuss the fate of peptides in cells before presentation by MHC complexes. We then discuss how peptides are altered post translationally to yield immune responses and how peptides can be engineered to achieve strong immune responses following vaccination. Although peptides are simple from a chemical perspective, they are complex in their immunological consequences. PMID- 24231620 TI - Effect of local bleomycin sulfate application on seroma formation in a rat mastectomy and axillary lymph node dissection model. AB - Seroma formation is one of the most common complications following breast cancer surgery. It may lead to delay of adjuvant therapies and increasement of therapy costs. Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It is locally used in the treatment of pleural effusion. The present study aimed to investigate seroma-reducing effect of local bleomycin application after mastectomy. Sixteen female Wistar Albino rats were used in this study. The rats were divided into two equal groups. Under general anesthesia all rats underwent unilateral mastectomy as definition by Harada. Serum physiologic was applied to animals in Group 1 (control group) and bleomycin to Group 2. Mastectomized localization was explored on the 10th day postoperatively. Seroma and tissue samples were obtained from axilla and thoracic wall for histopathological examination. The amount of seroma was significantly lower in the bleomycin group as compared to the control group (P=0.002). Fibrosis, PNL infiltration and the number of fibroblasts were significantly higher in the bleomycin group. No difference was identified between the groups in terms of angiogenesis, edema, congestion, and monocyte, lymphocyte and macrophage infiltration. Local bleomycin sulfate application might be a therapeutic option in patients with seroma formation, as well as in the patients with malignant pleural effusion. Nonetheless, further studies that compare the efficacy and adverse effects (benefit-to-harm ratio) of bleomycin sulfate are needed. PMID- 24231619 TI - Adaptive immune activation: glycosylation does matter. AB - Major histocompatibility complex (MHC) class I and II are glycoproteins that can present antigenic peptides at the cell surface for recognition and activation of circulating T lymphocytes. Here, the importance of the modification of protein antigens by glycans on cellular uptake, proteolytic processing, presentation by MHC and subsequent T-cell priming is reviewed. Antigen glycosylation is important for a number of diseases and vaccine design. All of the key proteins involved in antigen recognition and the orchestration of downstream effector functions are glycosylated. The influence of protein glycosylation on immune function and disease is covered. PMID- 24231621 TI - Causes of death and the impact of histiocytic sarcoma on the life expectancy of the Dutch population of Bernese mountain dogs and Flat-coated retrievers. AB - Bernese mountain dogs and Flat-coated retrievers are predisposed to hereditary oncological diseases. Since 1986 several authors have reported a high prevalence of tumours in both breeds, especially malignant histiocytosis/histiocytic sarcoma, which has a negative influence on life expectancy. However, many earlier reports included relatively low numbers of dogs, distributed over a small number of broad categories, often using outdated disease criteria. The aim of this study was to provide new data on causes of death, and the relative role of tumours, especially histiocytic sarcoma, collected and verified in a large number of dogs of both breeds in co-operation with dog owners and veterinarians. The study demonstrates that the death of at least 55.1% of Bernese mountain dogs and 63.8% of Flat-coated retrievers is associated with malignant tumours. In addition, it appears that over 1/7 of all Bernese mountain dogs and Flat-coated retrievers die because of histiocytic sarcoma. This emphasises the need for further research on tumours, especially histiocytic sarcoma. PMID- 24231622 TI - Recurrent hemarthrosis after total knee arthroplasty caused by the impingement of a remnant lateral meniscus: a case report. AB - A case of recurrent hemarthrosis initially presenting after the fifth postoperative month is described. Because of recurrent pain and swelling, the patient underwent an arthroscopy 14 months after total knee arthroplasty (TKA). A remnant posterior lateral meniscus was found to be impinged between the femoral component and the tibial liner, and there was oozing from the hypertrophied synovium around the remnant meniscus. The remnant meniscus and the synovium were carefully cauterized and completely excised. Following the arthroscopy, hemarthrosis has not recurred. A remnant lateral meniscus may be a cause of recurrent hemarthrosis after TKA. Accordingly, in cases of recurrent hemarthrosis after TKA, exploration by arthroscopy should be considered. PMID- 24231623 TI - Treatment of patella infera by patellar tendon lengthening and augmentation with tibialis anterior tendon allograft. AB - Management of patella infera remains a difficult therapeutic endeavor. We report a case of a 21-year-old man, who had development of patella infera and knee flexion contracture after a patella fracture. Patella infera was treated by patellar tendon lengthening and augmentation with a tibialis anterior tendon allograft fixed with bioabsorbable cross-pins. The patient regained an anatomic patellar position and full range of motion at two years after surgery. PMID- 24231624 TI - Diagnostic significance of periesophageal fat pad in ultrasonography for sliding hiatal hernias: sonographic fat pad sign. AB - The aim of the present study was to investigate the diagnostic significance of visualization of periesophageal fat pad in ultrasonography or computed tomography for sliding hiatal hernias. Forty-six controls and 21 esophageal hiatal hernia patients were compared in terms of sonographic and tomographic esophageal diameters. We suggest that absence of periesophageal fat pad sign in ultrasonography or computerized tomography is a noteworthy finding that calls for further investigation for the diagnosis of sliding hiatal hernias. PMID- 24231625 TI - Acute physiological response to aerobic short-interval training in trained runners. AB - PURPOSE: To analyze the acute physiological response to aerobic short-interval training (AESIT) at various high-intensity running speeds. A minor anaerobic glycolytic energy supply was aimed to mimic the characteristics of slow continuous runs. METHODS: Eight trained male runners (maximal oxygen uptake [VO(2max)] 55.5 +/- 3.3 mL . kg(-1) . min(-1)) performed an incremental treadmill exercise test (increments: 0.75 km . h(-1). min(-1)). Two lactate turn points (LTP1, LTP2) were determined. Subsequently, 3 randomly assigned AESIT sessions with high-intensity running-speed intervals were performed at speeds close to the speed (v) at VO(2max) (vVO(2max)) to create mean intensities of 50%, 55%, and 60% of vLTP1. AESIT sessions lasted 30 min and consisted of 10-s work phases, alternated by 20-s passive recovery phases. RESULTS: To produce mean velocities of 50%, 55%, and 60% of vLTP1, running speeds were calculated as 18.6 +/- 0.7 km/h (93.4% vVO(2max)), 20.2 +/- 0.6 km/h (101.9% vVO(2max)), and 22.3 +/- 0.7 km/h (111.0% vVO(2max)), which gave a mean blood lactate concentration (La) of 1.09 +/- 0.31 mmol/L, 1.57 +/- 0.52 mmol/L, and 2.09 +/- 0.99 mmol/L, respectively. La at 50% of vLTP1 was not significantly different from La at vLTP1 (P = .8894). Mean VO(2) was found at 54.0%, 58.5%, and 64.0% of VO(2max), while at the end of the sessions VO(2) rose to 71.1%, 80.4%, and 85.6% of VO(2max), respectively. CONCLUSION: The results showed that AESIT with 10-s work phases alternating with 20 s of passive rest and a running speed close to vVO(2max) gave a systemic aerobic metabolic profile similar to slow continuous runs. PMID- 24231626 TI - Cetuximab and non-small-cell lung cancer: end of the story? PMID- 24231627 TI - Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. AB - BACKGROUND: Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy. METHODS: In this unmasked, open-label randomised phase 3 trial we enrolled patients with metastatic, unresectable, or locally advanced NSCLC from 121 sites in Canada and the USA. Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen. Initially, patients were randomly assigned to receive either pemetrexed (500 mg/m(2)) or docetaxel (75 mg/m(2)) and then randomly assigned within each group to receive their chemotherapy with or without cetuximab (400 mg/m(2) at first dose and 250 mg/m(2) weekly thereafter) until disease progression or unacceptable toxicity. However, after a change in the standard of care, investigators chose whether to treat with pemetrexed or docetaxel on a patient-by patient basis. The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed, on an intention-to treat basis. This study is registered with ClinicalTrials.gov, number NCT00095199. FINDINGS: Between Jan 10, 2005, and Feb 10, 2010, we enrolled 939 patients; data for one patient was accidentally discarded. Of the remaining 938 patients, 605 received pemetrexed (301 patients with cetuximab and 304 alone) and 333 received docetaxel (167 in combination with cetuximab and 166 alone). Median progression-free survival with cetuximab plus pemetrexed was 2.9 months (95% CI 2.7-3.2) versus 2.8 months (2.5-3.3) with pemetrexed (HR 1.03, 95% CI 0.87-1.21; p=0.76). The most common grade 3-4 adverse events with cetuximab plus pemetrexed were fatigue (33 [11%] of 292 patients), acneiform rash (31 [11%]), dyspnoea (29 [10%]), and decreased neutrophil count (28 [10%]), and with pemetrexed alone were dyspnoea (35 [12%] of 289 patients), decreased neutrophil count (26 [9%]), and fatigue (23 [8%]). A significantly higher proportion of patients in the cetuximab plus pemetrexed group (119 [41%] of 292 patients) experienced at least one serious adverse event than those patients in the pemetrexed group (85 [29%] of 289 patients; p=0.0054). Nine (3%) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five (2%) of 289 treated patients in the pemetrexed alone group. INTERPRETATION: The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy. FUNDING: Eli Lilly and Company and ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company. PMID- 24231628 TI - Longitudinal speech perception and language performance in pediatric cochlear implant users: the effect of age at implantation. AB - OBJECTIVES: Few studies have examined the long-term effect of age at implantation on outcomes using multiple data points in children with cochlear implants. The goal of this study was to determine whether age at implantation has a significant, lasting impact on speech perception, language, and reading performance for children with prelingual hearing loss. DESIGN: A linear mixed model framework was used to determine the effect of age at implantation on speech perception, language, and reading abilities in 83 children with prelingual hearing loss who received cochlear implants by the age of 4 years. The children were divided into two groups based on their age at implantation: (1) under 2 years of age and (2) between 2 and 3.9 years of age. Differences in model specified mean scores between groups were compared at annual intervals from 5 to 13 years of age for speech perception, and 7 to 11 years of age for language and reading. RESULTS: After controlling for communication mode, device configuration, and preoperative pure-tone average, there was no significant effect of age at implantation for receptive language by 8 years of age, expressive language by 10 years of age, reading by 7 years of age. In terms of speech-perception outcomes, significance varied between 7 and 13 years of age, with no significant difference in speech-perception scores between groups at ages 7, 11, and 13 years. Children who used oral communication (OC) demonstrated significantly higher speech perception scores than children who used total communication (TC). OC users tended to have higher expressive language scores than TC users, although this did not reach significance. There was no significant difference between OC and TC users for receptive language or reading scores. CONCLUSIONS: Speech perception, language, and reading performance continue to improve over time for children implanted before 4 years of age. The present results indicate that the effect of age at implantation diminishes with time, particularly for higher-order skills such as language and reading. Some children who receive cochlear implants after the age of 2 years have the capacity to approximate the language and reading skills of their earlier-implanted peers, suggesting that additional factors may moderate the influence of age at implantation on outcomes over time. PMID- 24231629 TI - Objective measures of electrode discrimination with electrically evoked auditory change complex and speech-perception abilities in children with auditory neuropathy spectrum disorder. AB - OBJECTIVES: This study aimed to (1) determine the sensitivity of the electrically evoked auditory change complex (eACC) to changes in stimulating electrode position; and (2) investigate the association between results of eACC measures and behavioral electrode discrimination and their association with speech perception performance in pediatric cochlear implant (CI) users who have auditory neuropathy spectrum disorder (ANSD). DESIGN: Fifteen children with ANSD ranging in age between 5.4 and 18.6 years participated in this study. All subjects used Cochlear Nucleus devices. For each subject, open-set speech-perception ability was assessed using the Phonetically Balanced Kindergarten word lists presented at 60 dB SPL, using monitored live voice in a sound booth. Behavioral and objective measures of electrode discrimination were assessed in a nonclinical test environment. The stimuli used to elicit these measures were 800 msec biphasic pulse trains delivered by a direct interface to the CI. Data were collected from two basic stimulation conditions. In the standard condition, the entire pulse train was delivered to a mid-array electrode (electrode 11 or 12) at the maximum comfortable level (C level). In the change condition, the stimulus was split into two 400 msec pulse train segments presented sequentially on two different electrodes. The stimulation level of the second 400 msec pulse train was loudness balanced to the C level of the mid-array electrode used in the standard condition. The separation between the pair of stimulating electrodes was systematically varied. For behavioral electrode-discrimination measures, each subject was required to determine whether he or she heard one or two sounds for stimuli presented in different stimulation conditions. For the eACC measures, two replicates of 100 artifact-free sweeps were recorded for each stimulation condition. RESULTS: The eACC in response to changes in stimulating electrode position was recorded from all subjects with ANSD using direct electrical stimulation. Electrode-discrimination thresholds determined with the eACC and behavioral measures were consistent. Children with ANSD using CIs who showed poorer speech performance also required larger separations between the stimulating electrode pair to reliably elicit the eACC than subjects with better speech-perception performance. There was a robust correlation between electrode discrimination capacities and speech-perception performances in subjects tested in this study. The effect of electrode separation on eACC amplitudes was not monotonic. CONCLUSIONS: These results demonstrate the feasibility of using eACC to evaluate electrode-discrimination capacities in children with ANSD. These results suggest that the eACC elicited by changes in stimulating electrode position holds great promise as an objective tool for evaluating spectral-pattern detection in such subjects, which may be predictive of their potential speech perception performance. PMID- 24231630 TI - Surface induced collapse of Abeta1-42 with the F19A replacement following adsorption on a single walled carbon nanotube. AB - Spontaneous adsorption of the Abeta peptide on the surface of a single-walled carbon nanotube, resulting in the prevention of its intrinsic propensity to form collapsed states, could be a plausible means to hinder the peptide's initial nucleation and self-assembly. We report here the effects of sharply reducing both aromatic and hydrophobic character within the peptide's central hydrophobic core on its free and surface behavior. In such an altered peptide, complete surface adsorption is found to induce, rather than prevent, the adsorbed peptide's collapse. The weakened surface interactions of the central hydrophobic core allow its greater translational mobility on the surface, thereby facilitating interactions that lead to compaction. Both the adsorption and the subsequent collapse are accompanied by a loss of surface hydration in the modified peptide. We further find that such a two-step dewetting leads to hydration levels comparable to that obtained after compaction of the free peptide. These insights may be leveraged for designing molecular surfaces for disrupting intrinsic Abeta behavior. PMID- 24231631 TI - Comparison of an intensive pharmacist-managed telephone clinic with standard of care for tobacco cessation in a veteran population. AB - PURPOSE: To evaluate the effectiveness of the Pharmacist-Managed Telephone Tobacco Cessation Clinic (PMTTCC) compared to the standard of care (SOC) at the Veterans Affairs San Diego Healthcare System. METHOD: A retrospective cohort study was performed investigating the proportion of veterans who quit smoking at 6 months while enrolled in the PMTTCC. Chart review was performed using the Veterans Affairs Computerized Patient Record System. The PMTTCC group included patients who had received medication and counseling from the tobacco cessation pharmacists. The cohort was compared to a matched SOC group who did not receive counseling, only tobacco cessation medication therapy through a primary care provider. The primary outcome for this study was patient-reported tobacco cessation at 6 months. Secondary outcomes were abstinence at 1 and 3 months. RESULTS: A total of 1,006 patients were included in the analysis, 503 patients from the PMTTCC and 503 patients from SOC. The overall study population was 54 years old on average, 92.5% male, 70.0% Caucasian, 45.5% with history of psychiatric conditions, and had an average smoking history of 33-pack years. Patients in the PMTTCC group had statistically significant improvements in abstinence at 6 months versus the SOC group (81/503, 16.1% vs. 48/503, 9.5%; p < .0001). Quitters were older on average versus non-quitters (56.03 vs. 53.65 years; p = .01). CONCLUSION: Patients enrolled in the PMTTCC had improved tobacco abstinence rates at 6 months compared to SOC. Although the study was not designed to test for causality, the results lend support for using intensive tobacco cessation management in veteran population. PMID- 24231632 TI - Worksite health promotion program participation: a study to examine the determinants of participation. AB - This study explores the relationship between organizational health climate and worksite health promotion program participation, specifically engaging individuals who are unlikely to make positive health behavior choices on their own. Participants consisted of employees at three separate furniture manufacturing facilities completing a voluntary survey. Using responses (n = 349) from the health climate instrument, which is a measure of the collective attitudes, beliefs, and readiness to change a health behavior, this study identified two factors that were significant contributors to worksite health promotion program participation. Health norms, the collective attitudes regarding healthy lifestyle, as measured by the subscales-health scale and intention to make a behavior change-and "optimistic bias," the overassessment of one's personal health, were found to be predictors of participation. Additionally, significant (p < .05) predictors of self-assessed health, included perceived control to initiate, competence to carry out, and the organizational support of the health behavior change. The findings suggest that the organization's health norms and self-assessed health are associated with the worker's motivation to become involved with health promotion interventions. Offering worksite health screenings and advanced programming and creating a culture of health at work can help address program participation. PMID- 24231633 TI - An examination of stress in college students over the course of a semester. AB - The purpose of this study was to determine whether differing stress reduction interventions could alter stress levels experienced by male and female college students from the beginning to the end of a semester. Components of stress examined included overall perceived stress, test anxiety, and personal burnout. Participants (N = 531) were part of courses that during the course of a 16-week semester focused specifically on cognitive-behavioral stress management, cardiovascular fitness, generalized physical activity, or a control with no intervention. In addition to gender differences, both the stress management and physical activity groups had significantly lower levels of perceived stress, test anxiety, and personal burnout at the end of the semester. The fitness group scored significantly lower on perceived stress and personal burnout, but there was no difference in scores for test anxiety. The important ramifications of reducing stress in college students are discussed, including the pros and cons of implementing differing physical and psychological intervention modalities. PMID- 24231634 TI - Is the baby drowning in the bathwater? Exploring the fate of nurse educators in the modern university. PMID- 24231635 TI - Work values and intention to become a registered nurse among healthcare assistants. AB - PURPOSE: To examine the work values of Swiss healthcare assistant students, who, at the end of their vocational education in hospitals and nursing homes, choose to pursue a registered nurse degree. DESIGN: A prospective, cross-sectional survey was administered to a full cohort of healthcare assistant students in their last year of study in the canton of Bern (n=272). METHOD: Multivariate methods (logistic regression) were applied to estimate the joint effect of work experience and work values in choosing to pursue a registered nurse education. FINDINGS: Among work values, extrinsic values (regarding wage, career und educational perspectives) had a strong effect on the decisions of healthcare assistant students to pursue further education as registered nurses. Grades, socio-economic background and satisfaction during education also had an effect. CONCLUSIONS: Higher valuation of income, career and further education affect the career intentions of nursing assistants who have already obtained a recognized healthcare education and nursing experience. Teachers and trainers should actively identify the work values and expectations of these students. Provision of adequate advice and suggestions for the career development of these students may be an important route by which to address the nursing shortage and recruitment problems. PMID- 24231636 TI - The influence of personal qualities on performance and progression in a pre registration nursing programme. AB - BACKGROUND: Research conducted primarily with psychology and medical students has highlighted that personal qualities play an important role in students' academic performance. In nursing there has been limited investigation of the relationship between personal qualities and performance. Yet, reports of student incivility and a lack of compassion have prompted appeals to integrate the assessment of personal qualities into pre-registration nursing student selection. Before this can be done research is needed to explore the influence of students' personal qualities on programme performance and progression. AIM: This study explores the relationships between students' personal qualities and their academic and clinical performance, behaviours and progression through a pre-registration nursing programme in Australia. METHOD: This longitudinal descriptive correlational study was undertaken with a sample of Australian pre-registration nursing students (n=138). Students' personal qualities were assessed using three personal qualities assessment (PQA) instruments. Outcome measures included grades in nursing theory and clinical courses, yearly grade point average, final clinical competency, progression (completion), class attendance and levels of life event stress. RESULTS: Significant correlations were found between academic performance and PQA scores for self-control, resilience and traits of aloofness, confidence and involvement. Final clinical competence was predicted by confidence and self-control scores. Students with higher empathy had higher levels of life event stress in their first year and class attendance had a positive correlation with self-control. Completing the programme in three years was weakly predicted by the measure of resilience. No difference was noted between extreme or non extreme scorers on the PQA scales with respect to performance or progression. CONCLUSION: This sample of students' personal qualities was found to influence their academic and clinical performance and their ability to complete a pre registration programme in three years. However, further research is required with larger cohorts to confirm the use of personal qualities assessment during selection. PMID- 24231637 TI - Use of virtual clinical simulation to improve communication skills of baccalaureate nursing students: a pilot study. AB - BACKGROUND: According to The Joint Commission (2012), the leading cause of sentinel events in the United States was miscommunication. Lack of thorough and accurate communication remains a serious challenge in healthcare and an educational priority in schools of nursing. Virtual clinical simulation is an online educational approach where students use avatars to practice various skills. OBJECTIVES: The purpose of this pilot study was to evaluate the educational innovation of using virtual clinical simulation to improve communication skills of BSN students. The objectives of the simulations were to 1) recognize significant patient data and 2) accurately perform the ISBAR communication technique. DESIGN: The study used a within-group, time-series design with eight students. Students participated in two synchronous virtual simulations in an online virtual clinical environment called CliniSpace. Students performed in groups of four to five students. METHODS: Students performed in two virtual simulations in groups of four to five students. Student performances were scored by two raters using the CliniSpace ISBAR Rating Sheet. Field notes from debriefing sessions were analyzed for content. RESULTS: Mean group student performance scores more than doubled from performance one to performance two. This change was found to be statistically significant, p<.001. Field notes revealed that students listened to how their peers communicated and learned from them. Students expressed having less anxiety, knowing what to expect, and having "better flow" with communication. Students verbalized learning to assess the patient prior to calling the physician and to give a recommendation to the physician. PMID- 24231638 TI - [Research in paediatric emergencies]. PMID- 24231639 TI - Higher protein intake improves length, not weight, z scores in preterm infants. AB - OBJECTIVE: The aim of the study was to evaluate the relation between nutritional intake (kilocalories, protein) and weight and length growth in preterm infants, and to describe their metabolic tolerance with a focus on those with high protein intake (>= 4.6 g . kg(-1) . day(-1)). METHODS: Secondary analysis of data from appropriate-for-gestational age preterm infants in a 28-day randomized clinical trial that evaluated growth, tolerance, and safety of a new ultraconcentrated liquid human milk fortifier (original study n = 150). This subset of 56 infants had complete growth and nutrition data and met criteria for the original study's "efficacy analysis" (eg, >80% of kilocalorie intake from study diet). Nutritional intake was estimated, not actual. Regressions were used to test cumulative kilocalories and protein as the predictors of 28-day change in weight and length z scores (growth status), and to evaluate protein tolerance. RESULTS: Average intake was 118 +/- 8 kcal . kg(-1) . day(-1) and 4.3 +/- 0.4 g protein . kg(-1) . day(-1), with 16 +/- 3 g . kg(-1) . day(-1) and 1.1 +/- 0.2 cm/week growth for 28 days. Cumulative total kilocalories and protein were significant predictors of improved length z score (P = 0.0054, 0.0005) but not weight z score change. Regression models indicated that protein not kilocalories explained the improvement in length z score, with protein explaining 19% of the variability. The high protein group averaged 4.6 to 5.5 g . kg(-1) . day(-1) (n = 16). Protein tolerance was adequate for all of the study infants based on metabolic measures (blood urea nitrogen, serum carbon dioxide, pH). CONCLUSIONS: Higher cumulative protein intake was tolerated and overall lessened the commonly occurring decline in the length but not weight growth status in a 28-day study of preterm infants. PMID- 24231640 TI - Anti-CD20 Monoclonal Antibody Therapy in Functional Bile Salt Export Pump Deficiency After Liver Transplantation. PMID- 24231641 TI - Authors' reply. PMID- 24231642 TI - Atopic eczema could be a cause and not an effect of cow's milk protein allergy. PMID- 24231643 TI - Long-term outcome of home parenteral nutrition in patients with ultra-short bowel syndrome. AB - OBJECTIVE: The patients with ultra-short bowel syndrome (U-SBS) have been considered potential candidates for a preemptive/rehabilitative intestinal transplantation owing to the high risk of death from the underlying disease. We hypothesized that children with U-SBS, in the absence of intestinal failure associated liver disease (IFALD), could also have a good rate of survival on home parenteral nutrition (HPN). METHODS: A prospective database from the "Bambino Gesu" Artificial Nutrition and Intestinal Failure Program was used to evaluate outcomes and morbidities of consecutive patients with <= 10 cm of small bowel enrolled since 2000. RESULTS: Eleven patients were identified with a median bowel length of 7.5 (3-9) cm. Eight patients developed IFALD, which reversed in 7 of them; the IFALD progressively worsened in 1 patient until death. One patient underwent isolated intestinal transplantation and 1 patient is no longer receiving parenteral nutrition (PN) and both are fully enterally fed. The other patients remained at least partially dependent on HPN. The number of days of inpatient care decreased in all of the patients except for the 1 who had repeated episodes of central line infections. CONCLUSIONS: The survival of patients with U SBS receiving HPN was good. Although IFALD was frequent, it had been manageable in most of the patients, but in a single complex case, it led to death. The multidisciplinary management warranted to these patients to approach the school age, to grow, and to maintain the oral intake. Patients with U-SBS are rare, and to better understand their long-term survival, further studies, including more large patient populations, are required. PMID- 24231644 TI - ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. AB - BACKGROUND: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. METHODS: We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. RESULTS: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy. CONCLUSIONS: These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum. PMID- 24231645 TI - Autoantibody and human leukocyte antigen profiles in children with autoimmune liver disease and their first-degree relatives. AB - OBJECTIVE: Familial clustering of juvenile autoimmune liver disease (AILD), including autoimmune hepatitis and autoimmune sclerosing cholangitis (ASC), is rare, despite a high prevalence of autoimmune disorders in AILD families. METHODS: To investigate this discrepancy, we measured autoantibodies diagnostic for AILD, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and anti-soluble liver antigen antibodies, and human leukocyte antigen profiles in 31 patients and 65 of their first-degree relatives (FDR). The autoantibody profile was compared with that of 42 healthy subjects (HS). RESULTS: Autoantibodies were detected in 71% (22/31) patients. Anti-nuclear antibody or anti-smooth muscle antibody were present in 4/65 FDR (6.2%). HS were negative for all autoantibodies. The frequencies of homozygous HLA DRB1*0301 (DR3) genes and haplotype A1-B8-DR3 were higher in the patients (25% and 43%) than in FDR (9% and 27%) and HS (0% and 16%). The frequencies of disease protective genes DR4 and/or DR15 were lower in the patients (25%) than in FDR (42%) and HS (42%). Only 1 family contained 2 patients with AILD, 1 with ASC and 1 with primary sclerosing cholangitis. Both patients possessed A1-B8-DR3 genes, the ASC being homozygous and the primary sclerosing cholangitis heterozygous. Six FDR had nonhepatic autoimmune disorders, none being autoantibody positive. CONCLUSIONS: Homozygosity for DR3 plays a major role in the predisposition to juvenile AILD. Diagnostic autoantibodies for AILD are rare among patients' FDR and not linked to clinical manifestation of AILD. PMID- 24231646 TI - Humoral immunity after kidney transplantation: impact of two randomized immunosuppressive protocols. AB - BACKGROUND: Controlling alloimmune humoral response is a challenge in transplantation. Few studies have evaluated the impact of maintenance immunosuppression on blood humoral parameters. MATERIAL/METHODS: We performed a post-hoc analysis on 307 kidney transplant recipients included in a prospective randomized trial comparing tacrolimus/mycophenolate mofetil (Tac/MMF) vs. cyclosporine/azathioprine (CsA/AZA), both used with antithymocyte globulin induction and steroids. Humoral parameters were analyzed at D0, D15, and M12. RESULTS: IgG, IgA, and IgM levels decreased significantly as soon as D15 in both groups (-35%, -26%, and -35% respectively, vs. D0). At M12, although peripheral B cell counts did not differ between the groups, Tac/MMF regimen was associated with lower IgG, IgA, and IgM levels than CsA/AZA (-5.9%, -14.6%, and -34%, respectively). Hypogammaglobulinemia at D15 was not associated with an increased risk of infections during the first year. The proportion of HLA-sensitized patients decreased in the Tac/MMF group (15.9% at D0 and 6.7% at M12, p=0.02) and remained stable in the CsA/AZA group (10.3% at D0 and 8.9% at M12, p=0.5). More patients sensitized at baseline became non-sensitized at M12 with Tac/MMF than with CsA/AZA. CONCLUSIONS: Our results suggest humoral immunosuppression is better with Tac/MMF than with CsA/AZA during the first year of kidney transplantation. PMID- 24231647 TI - WITHDRAWN: Transplantation of mesenchymal stem cells recruits trophic macrophages to induce pancreatic beta cell regeneration in diabetic mice. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 24231648 TI - Monte Carlo simulations of nanoscale focused neon ion beam sputtering. AB - A Monte Carlo simulation is developed to model the physical sputtering of aluminum and tungsten emulating nanoscale focused helium and neon ion beam etching from the gas field ion microscope. Neon beams with different beam energies (0.5-30 keV) and a constant beam diameter (Gaussian with full-width-at half-maximum of 1 nm) were simulated to elucidate the nanostructure evolution during the physical sputtering of nanoscale high aspect ratio features. The aspect ratio and sputter yield vary with the ion species and beam energy for a constant beam diameter and are related to the distribution of the nuclear energy loss. Neon ions have a larger sputter yield than the helium ions due to their larger mass and consequently larger nuclear energy loss relative to helium. Quantitative information such as the sputtering yields, the energy-dependent aspect ratios and resolution-limiting effects are discussed. PMID- 24231649 TI - Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. AB - During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs. PMID- 24231651 TI - The Swedish Developmental Biology Organization (SWEDBO): a new beginning. PMID- 24231650 TI - Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection. AB - Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 MUM, alphaKA of 0.38MUM and a beta value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid binding, whereas the larger inhibitor 23d blocks the enzyme active site. PMID- 24231652 TI - Higher pain perception and lack of recovery from neuropathic pain in females: a behavioural, immunohistochemical, and proteomic investigation on sex-related differences in mice. AB - In experimental and clinical pain studies, the sex of subjects was rarely taken into account, even if nociceptive inputs appear to be processed and modulated by partially distinct neural mechanisms in each sex. In this study we analysed, in male and female mice, behavioural and neuronal responses in developing, maintaining, and recovering from neuropathic pain. Experiments were carried out in adult CD1 mice by using Chronic Constriction Injury (CCI) as neuropathic pain model. We investigated the temporal trend of mechanical nociceptive threshold together with functional recovery of the injured paw, and the immunofluorescence staining of proteins associated with nerve injury and repair and with spinal gliosis, 7 and 121days after CCI. A proteomic analysis on proteins extracted from sciatic nerves was also performed. Male mice showed a gradual decrease of CCI induced allodynia, the complete recovery occurring 81days after the sciatic nerve ligation. On the contrary, in female mice, allodynia was still present 121days after CCI. Sex-dependent differences also resulted from immunofluorescence experiments: in sciatic nerve, the expression of P0 and Neu200 is greater in neuropathic males than in neuropathic females, suggesting faster nerve regeneration. Proteomic analysis confirmed sex-related differences of proteins associated with nerve regenerative processes. In addition, the reactive gliosis induced by CCI at day 7, as revealed by colocalization of glial fibrillary acidic protein (astrocytes) and CD11b (microglia) with phosphorylated p38, disappeared 121 days after CCI in male but not in female mice. These results may have important therapeutic implications for the treatment of neuropathic pain. PMID- 24231653 TI - The role of executive functioning in children's attentional pain control: an experimental analysis. AB - Directing attention away from pain is often used in children's pain treatment programs to control pain. However, empirical evidence concerning its effectiveness is inconclusive. We therefore sought to understand other influencing factors, including executive function and its role in the pain experience. This study investigates the role of executive functioning in the effectiveness of distraction. School children (n=164) completed executive functioning tasks (inhibition, switching, and working memory) and performed a cold-pressor task. One half of the children simultaneously performed a distracting tone-detection task; the other half did not. Results showed that participants in the distraction group were engaged in the distraction task and were reported to pay significantly less attention to pain than controls. Executive functioning influenced distraction task engagement. More specifically, participants with good inhibition and working memory abilities performed the distraction task better; participants with good switching abilities reported having paid more attention to the distraction task. Furthermore, distraction was found to be ineffective in reducing pain intensity and affect. Executive functioning did not influence the effectiveness of distraction. However, a relationship was found between executive functioning and pain affect, indicating that participants with good inhibition and working memory abilities experienced the cold-pressor task as less stressful and unpleasant. Our findings suggest that distraction as a process for managing pain is complex. While it appears that executive function may play a role in adult distraction, in this study it did not direct attention away from pain. It may instead be involved in the overall pain experience. PMID- 24231654 TI - Onset of action of a lozenge containing flurbiprofen 8.75 mg: a randomized, double-blind, placebo-controlled trial with a new method for measuring onset of analgesic activity. AB - A new onset-of-action model was utilized to distinguish the pharmacologic activity of flurbiprofen 8.75mg delivered in a lozenge from the demulcent effect of the lozenge base. In a randomized, double-blind, placebo-controlled trial, patients with sore throat rated pain on a Sore Throat Pain Intensity Scale before taking one flurbiprofen or placebo lozenge and at frequent (2-minute) intervals over the first hour after treatment. Further ratings of the Sore Throat Pain Intensity Scale and other patient-reported outcomes (difficulty swallowing, swollen throat, pain relief) were obtained at varying intervals over 6 hours. Onset of pharmacologic activity was defined as the median time of first perceived pain reduction if a patient reported clinically meaningful (at least moderate) relief. The conventional method of comparing mean treatment responses at each time point was also implemented. Demulcent action was detected at the first 2 minute assessment. By the new method, 102 flurbiprofen-treated patients were identified as first perceiving pain relief at 12 minutes, compared with >120 minutes by 102 patients using placebo (P<0.001). By the conventional method, mean percentage pain reduction for flurbiprofen 8.75 mg was first significantly differentiated from placebo at 26 minutes (P<0.05). Efficacy of flurbiprofen lozenge was demonstrated for 3.5-4hours on the 4 patient-reported outcomes (all P<0.05 compared with placebo). There were no serious adverse events. This patient centered onset-of-action model identifies the initiation of pain relief in patients who are definite drug responders, here demonstrating that a flurbiprofen 8.75-mg lozenge provides early relief of sore throat. PMID- 24231655 TI - The braking force in walking: age-related differences and improvement in older adults with exergame training. AB - The purposes of this present research were, in the first study, to determine whether age impacts a measure of postural control (the braking force in walking) and, in a second study, to determine whether exergame training in physically simulated sport activity would show transfer, increasing the braking force in walking and also improving balance assessed by clinical measures, functional fitness, and health-related quality of life in older adults. For the second study, the authors developed an active video game training program (using the Wii system) with a pretest-training-posttest design comparing an experimental group (24 1-hr sessions of training) with a control group. Participants completed a battery comprising balance (braking force in short and normal step conditions), functional fitness (Senior Fitness Test), and health-related quality of life (SF 36). Results show that 12 weeks of video game-based exercise program training improved the braking force in the normal step condition, along with the functional fitness of lower limb strength, cardiovascular endurance, and motor agility, as measured by the Senior Fitness Test. Only the global mental dimension of the SF-36 was sensitive to exergame practice. Exergames appear to be an effective way to train postural control in older adults. Because of the multimodal nature of the activity, exergames provide an effective tool for remediation of age-related problems. PMID- 24231656 TI - Taking the STING out of cytosolic DNA sensing. AB - Detection of cytosolic DNA activates a downstream signaling molecule called STimulator of INterferon Genes (STING). Inappropriate or excessive activation of STING can lead to autoimmune disease. A new paper in Cell addresses the important question of how STING-dependent signaling is normally constrained. PMID- 24231657 TI - Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm. AB - BACKGROUND: Human ascending thoracic aortic aneurysms (ATAAs) are life threatening and constitute a leading cause of mortality in the United States. Previously, we demonstrated that collagens alpha2(V) and alpha1(XI) mRNA and protein expression levels are significantly increased in ATAAs. METHODS AND RESULTS: In this report, the authors extended these preliminary studies using high-throughput proteomic analysis to identify additional biomarkers for use in whole blood real-time RT-PCR analysis to allow for the identification of ATAAs before dissection or rupture. Human ATAA samples were obtained from male and female patients aged 65 +/- 14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of ATAAs using qRT-PCR analysis of whole blood. Analysis of 41 samples (19 small, 13 medium-sized, and 9 large ATAAs) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with ATAA of >=4.0 cm (P<0.001, sensitivity 0.79, CI=0.62 to 0.91; specificity 1.00, 95% CI=0.42 to 1.00). CONCLUSION: A preliminary transcript biomarker panel for the identification of ATAAs using whole blood qRT-PCR analysis in men and women is presented. PMID- 24231658 TI - Incidence and risk factors of cerebrovascular events following cardiac catheterization. AB - BACKGROUND: One of the most daunting complications of cardiac catheterization is a cerebrovascular event (CVE). We aimed to assess the real-life incidence, etiology, and risk factors of cardiac catheterization-related acute CVEs in a large cohort of patients treated in a single center. METHODS AND RESULTS: We undertook a retrospective analysis of 43,350 coronary procedures performed on 30,907 procedure days over the period 1992-2011 and compared patient and procedural characteristics of procedures complicated by CVEs with the remaining cohort. CVEs occurred in 47 cases: 43 were ischemic, 3 intracerebral hemorrhages, and 1 undetermined. The overall CVE rate was 0.15%, with percutaneous coronary intervention (PCI) and diagnostic coronary angiography rates 0.23% and 0.09%, respectively. Using a forward stepwise multivariate logistic regression model including patient demographic and procedural characteristics, a total of 5 significant predictors were defined: prior stroke (OR=15.09, 95% CI [8.11 to 28.08], P<0.0001), presence of coronary arterial thrombus (OR=2.79, 95% CI [1.25 to 6.22], P=0.012), age >75 years (OR=3.33, 95% CI [1.79 to 6.19], P<0.0001), triple vessel disease (OR=2.24, 95% CI [1.20 to 4.18], P=0.011), and performance of intervention (OR=2.21, 95% CI [1.12 to 4.33], P=0.021). An additional analysis excluded any temporal change of CVE rates but demonstrated a significant increase of all high-risk patient features. CONCLUSION: In a single-center, retrospective assessment over nearly 20 years, cardiac catheterization-related CVEs were very rare and nearly exclusively ischemic. The independent predictors for these events were found to be the performance of an intervention and those associated with increased atherosclerotic burden, specifically older age, triple vessel disease, and prior stroke. The presence of intracoronary thrombus appears also to raise the risk of procedure-related CVE. PMID- 24231659 TI - Protein phosphatase 1 inhibitor-1 deficiency reduces phosphorylation of renal NaCl cotransporter and causes arterial hypotension. AB - The thiazide-sensitive NaCl cotransporter (NCC) of the renal distal convoluted tubule (DCT) controls ion homeostasis and arterial BP. Loss-of-function mutations of NCC cause renal salt wasting with arterial hypotension (Gitelman syndrome). Conversely, mutations in the NCC-regulating WNK kinases or kelch-like 3 protein cause familial hyperkalemic hypertension. Here, we performed automated sorting of mouse DCTs and microarray analysis for comprehensive identification of novel DCT enriched gene products, which may potentially regulate DCT and NCC function. This approach identified protein phosphatase 1 inhibitor-1 (I-1) as a DCT-enriched transcript, and immunohistochemistry revealed I-1 expression in mouse and human DCTs and thick ascending limbs. In heterologous expression systems, coexpression of NCC with I-1 increased thiazide-dependent Na(+) uptake, whereas RNAi-mediated knockdown of endogenous I-1 reduced NCC phosphorylation. Likewise, levels of phosphorylated NCC decreased by approximately 50% in I-1 (I-1(-/-)) knockout mice without changes in total NCC expression. The abundance and phosphorylation of other renal sodium-transporting proteins, including NaPi-IIa, NKCC2, and ENaC, did not change, although the abundance of pendrin increased in these mice. The abundance, phosphorylation, and subcellular localization of SPAK were similar in wild-type (WT) and I-1(-/-) mice. Compared with WT mice, I-1(-/-) mice exhibited significantly lower arterial BP but did not display other metabolic features of NCC dysregulation. Thus, I-1 is a DCT-enriched gene product that controls arterial BP, possibly through regulation of NCC activity. PMID- 24231660 TI - A within-patient analysis for time-varying risk factors of CKD progression. AB - Recent data suggest that nonlinear GFR trajectories are common among patients with CKD, but the modifiable risk factors underlying these changes in CKD progression rate are unknown. Analyses relating baseline risk factors to subsequent GFR decline are suboptimal because these relationships often attenuate as follow-up time increases and these analyses do not account for temporal changes in risk factors. We identified 74 participants in the African American Study of Kidney Disease and Hypertension who had both a period of rapid GFR decline and an extended period of stability during a follow-up period of >=12 years. We performed a within-patient comparison of time-varying risk factors measured during the periods of GFR decline and stability and identified several risk factors associated with faster GFR decline: more hospitalization episodes and hospitalization days per year; higher BP, serum phosphorus, and urine protein to-creatinine ratio; lower serum albumin and urine sodium-to-potassium ratio; slower rate of decline of serum urea nitrogen, serum creatinine, serum uric acid, and serum phosphorus; and faster rate of decline of serum hematocrit and serum bicarbonate. By allowing each patient to serve as his or her own control, this novel, within-patient analytic approach holds considerable promise as a means to identify time-varying risk factors associated with stabilization of GFR or acceleration of GFR decline. PMID- 24231661 TI - Functional cardiopulmonary exercise testing in potential renal transplant recipients. PMID- 24231663 TI - Plasma apolipoprotein L1 levels do not correlate with CKD. AB - Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1 associated kidney disease in HIV-infected African Americans. PMID- 24231662 TI - The gut microbiome, kidney disease, and targeted interventions. AB - The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms. PMID- 24231664 TI - Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion. AB - Dialytic clearance of urea is efficient, but other small solutes normally secreted by the kidney may be cleared less efficiently. This study tested whether the high concentrations of these solutes in hemodialysis patients reflect a failure of passive diffusion methods to duplicate the efficacy of clearance by tubular secretion. We compared the plasma concentrations and clearance rates of four solutes normally cleared by tubular secretion with the plasma concentrations and clearance rates of urea and creatinine in patients receiving maintenance hemodialysis and normal subjects. The predialysis concentrations (relative to normal subjects) of unbound phenylacetylglutamine (122-fold), hippurate (108 fold), indoxyl sulfate (116-fold), and p-cresol sulfate (41-fold) were much greater than the concentrations of urea (5-fold) and creatinine (13-fold). The dialytic clearance rates (relative to normal subjects) of unbound phenylacetylglutamine (0.37-fold), hippurate (0.16-fold), indoxyl sulfate (0.21 fold), and p-cresol sulfate (0.39-fold) were much lower than the rates of urea (4.2-fold) and creatinine (1.3-fold). Mathematical modeling showed that prominent accumulation of the normally secreted solutes in hemodialysis patients could be accounted for by lower dialytic clearance relative to physiologic clearance combined with the intermittency of treatment. Whether or not more efficient removal of normally secreted solutes improves outcomes in dialysis patients remains to be tested. PMID- 24231665 TI - Economic evaluation of frequent home nocturnal hemodialysis based on a randomized controlled trial. AB - Provider and patient enthusiasm for frequent home nocturnal hemodialysis (FHNHD) has been renewed; however, the cost-effectiveness of this technique is unknown. We performed a cost-utility analysis of FHNHD compared with conventional hemodialysis (CvHD; 4 hours three times per week) from a health payer perspective over a lifetime horizon using patient information from the Alberta NHD randomized controlled trial. Costs, including training costs, were obtained using microcosting and administrative data (CAN$2012). We determined the incremental cost per quality-adjusted life year (QALY) gained. Robustness was assessed using scenario, sensitivity, and probabilistic sensitivity analyses. Compared with CvHD (61% in-center, 14% satellite, and 25% home dialysis), FHNHD led to incremental cost savings (-$6700) and an additional 0.38 QALYs. In sensitivity analyses, when the annual probability of technique failure with FHNHD increased from 7.6% (reference case) to >=19%, FHNHD became unattractive (>$75,000/QALY). The cost/QALY gained became $13,000 if average training time for FHNHD increased from 3.7 to 6 weeks. In scenarios with alternate comparator modalities, FHNHD remained dominant compared with in-center CvHD; cost/QALYs gained were $18,500, $198,000, and $423,000 compared with satellite CvHD, home CvHD, and peritoneal dialysis, respectively. In summary, FHNHD is attractive compared with in-center CvHD in this cohort. However, the attractiveness of FHNHD varies by technique failure rate, training time, and dialysis modalities from which patients are drawn, and these variables should be considered when establishing FHNHD programs. PMID- 24231666 TI - Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. AB - Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for <=5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT <40% of predicted peak VO2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT >=40% (P<0.001). Regarding the cohort with AT <40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT >=40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant. PMID- 24231667 TI - Three-dimensional solid texture analysis in biomedical imaging: review and opportunities. AB - Three-dimensional computerized characterization of biomedical solid textures is key to large-scale and high-throughput screening of imaging data. Such data increasingly become available in the clinical and research environments with an ever increasing spatial resolution. In this text we exhaustively analyze the state-of-the-art in 3-D biomedical texture analysis to identify the specific needs of the application domains and extract promising trends in image processing algorithms. The geometrical properties of biomedical textures are studied both in their natural space and on digitized lattices. It is found that most of the tissue types have strong multi-scale directional properties, that are well captured by imaging protocols with high resolutions and spherical spatial transfer functions. The information modeled by the various image processing techniques is analyzed and visualized by displaying their 3-D texture primitives. We demonstrate that non-convolutional approaches are expected to provide best results when the size of structures are inferior to five voxels. For larger structures, it is shown that only multi-scale directional convolutional approaches that are non-separable allow for an unbiased modeling of 3-D biomedical textures. With the increase of high-resolution isotropic imaging protocols in clinical routine and research, these models are expected to best leverage the wealth of 3-D biomedical texture analysis in the future. Future research directions and opportunities are proposed to efficiently model personalized image-based phenotypes of normal biomedical tissue and its alterations. The integration of the clinical and genomic context is expected to better explain the intra class variation of healthy biomedical textures. Using texture synthesis, this provides the exciting opportunity to simulate and visualize texture atlases of normal ageing process and disease progression for enhanced treatment planning and clinical care management. PMID- 24231668 TI - End-tidal concentrations of sevoflurane and desflurane for ProSeal laryngeal mask airway removal in anaesthetised adults: a randomised double-blind study. AB - BACKGROUND: The optimal end-tidal sevoflurane and desflurane concentration for successful ProSeal laryngeal mask airway (PLMA) removal in unpremedicated anaesthetised adults has not been determined. OBJECTIVES: We determined end-tidal sevoflurane and desflurane concentration in 50% of anaesthetised adults (EC50: concentration at which there is 50% chance of patients showing 'no movement' response) for smooth PLMA removal. DESIGN: Randomised controlled double blind study. SETTING: Operating theatre of a government tertiary care institute. The study period was December 2011 to January 2013. PATIENTS: Thirty nine unpremedicated American Society of Anesthesiologists (ASA) physical status I and II women with cervical carcinoma (aged 30 to 60 years) scheduled for implantation of intracavity caesium under general anaesthesia with PLMA as an airway device were included in the study. INTERVENTIONS: The participants were randomised to one of the two groups receiving either desflurane or sevoflurane for anaesthesia maintenance. Anaesthesia induction was performed with intravenous propofol. Predetermined end-tidal sevoflurane concentration (initiating at 2%) or desflurane (initiating at 4%) was sustained for 10 min before PLMA removal was attempted. End-tidal concentrations were increased/decreased (step-size 0.2% for sevoflurane and 0.5% for desflurane) using Dixon and Massey up and down method in the next patient depending upon previous patient's response. Patient responses to PLMA removal were classified as 'movement' or 'no movement'. MAIN OUTCOME MEASURES: EC50 was calculated as the mean of the crossover pairs' midpoints in each group and further confirmed by probit regression analysis. RESULTS: EC50 (95% confidence interval) of sevoflurane and desflurane for PLMA removal were 1.58% (0.669 to 2.060) and 2.79% (2.733 to 2.841), respectively. CONCLUSION: Predicted EC50 and EC95 of sevoflurane and desflurane for smooth removal for the PLMA were 1.58 (0.669 to 2.060), 2.27 (1.859 to 21.16), 2.79 (2.733.2.841) and 3.27% (3.173 to 3.395), respectively. TRIAL REGISTRATION: Registered with Clinical Trial Registry of India (URL: http://www.ctri.in), Registry ref no: CTRI/2012/12/004285. PMID- 24231669 TI - Enhanced trion emission from colloidal quantum dots with photonic crystals by two photon excitation. AB - For colloidal quantum dots, the ongoing biggest problem is their fluorescence blinking. Until now, there is no generally accepted model for this fluorescence blinking. Here, two-photon excited fluorescence from CdSe/ZnS nanocrystals on silicon nitride photonic crystals is studied using a femtosecond laser. From analysis of the spectra and decay processes, most of the relative trion efficiency is larger than 10%, and the largest relative trion efficiency reaches 46.7%. The photonic crystals enhance the trion emission of CdSe/ZnS nanocrystals, where the enhancement is due to the coupling of the trion emission to the leaky mode of the photonic crystal slab. Moreover, the photonic crystals enhance the Auger-assisted trapping efficiency of electrons/holes to surface states, and then enhance the efficiency of the generations of charge separation and DC electric field, which modifies the trion spectrum. Therefore, a model is present for explaining the mechanism of fluorescence blinking including the effect of the environment. PMID- 24231670 TI - Adoption of sun safe workplace practices by local governments. AB - CONTEXT: Outdoor workers are especially susceptible to skin cancer--the most common, but also one of the most preventable, forms of cancer. Colorado, the location of the study, has the second highest rate of skin cancer deaths in the nation. OBJECTIVE: Local government managers in Colorado-in municipalities, counties, and special districts-were surveyed to ascertain the extent to which they engage in formal (written) and informal practices to protect their outdoor workers against excessive exposure to sun. DESIGN: The survey consisted of 51 questions assessing awareness of formal or informal practices for sun protection of outdoor workers. An index of practices--the study's dependent variable--was created that was composed or practices such as providing employees free or reduced-cost sunscreen, wide-brimmed hats, sunglasses, long-sleeved work shirts, long work pants, and temporary or permanent outdoor shade shelters. Proscriptive policies, such as restricting the use of broad brimmed hats, were subtracted from the index. Surveys were completed by 825 administrators representing 98 jurisdictions. Responses from administrators in the same jurisdiction were averaged. RESULTS: More than 40% of responding jurisdictions indicated that they engaged in informal sun safety practices. Tests conducted to determine what variables might account for the adoption of these sun protection practices found that the degree to which a community could be regarded as cosmopolite and as having an individualistic political culture were significant predictors. Type of government was also significant. Although, higher community income was a significant predictor, neither local government budget nor size was significant. CONCLUSIONS: The adoption of sun safe practices bears low costs with potentially high returns. Findings from this study suggest that awareness campaigns might most effectively target cosmopolite communities, but that the greatest impact might be achieved by targeting localite communities. Government size and budget do not appear to be constraints in the adoption of sun safe practices. PMID- 24231671 TI - Results of arthroscopic treatment of rotator cuff tear with the resection of symptomatic acromioclavicular joint with degenerative changes. AB - BACKGROUND: Rotator cuff (RC) tear is one of the most common disorders affecting the shoulder. Acromioclavicular (AC) joint arthritis is an equally common pathology of the shoulder. The coexistence of both disorders is common, although RC tear is more frequently the cause of shoulder pain than AC joint arthritis. The purpose of this study was to compare the results of arthroscopic treatment of RC tear and simultaneous resection of symptomatic AC joint with arthritis. MATERIAL/METHODS: We retrospectively evaluated 40 patients who underwent arthroscopic RC repair between January 2008 and December 2009. Patients were divided into two groups. The first group consisted of 20 patients with symptomatic arthritis of AC joint, specifically painful joint palpation test and painful cross-body adduction test. The control group included 20 patients with asymptomatic degenerative changes of AC joint. The first group of patients underwent RC resection and AC joint repair; the second group had an isolated RC repair. Follow-up period lasted from 44 to 68 months, an average of 54.4 months. RESULTS: Analysis using chi-squared test for independence has shown no statistically significant difference in terms of subjects' gender or age in both groups. No significant difference in terms of pain intensity (VAS) was observed before and after surgery in either group. Significant reduction in pain intensity after surgery was observed in both groups, the AC joint resection group (p<0.001) and the without joint resection group (p<0.001). An increase in Constant's scale score was recorded in both groups after the surgery. Analysis has shown that patients who had undergone AC joint resection, had lower scores on a Constant's scale (p<0.022) before the surgery than those who were not resected. There were no statistically significant differences between the two groups after the surgery. CONCLUSIONS: Supplementary resection of a painful AC joint with arthritis during RC tear repair provides good, long-term outcomes. In contrast to patients with asymptomatic AC joint arthritis, the coexistence of a torn RC and symptomatic AC joint with arthritis, can worsen shoulder function in the preoperative period. PMID- 24231672 TI - The antennal sensilla of the praying mantis Tenodera aridifolia: a new flagellar partition based on the antennal macro-, micro- and ultrastructures. AB - In insects, the antenna consists of a scapus, a pedicellus, and a flagellum comprising many segments (flagellomeres). These segments possess many morphological types of sensory organs (sensilla) to process multimodal sensory information. We observed the sensilla on flagellomeres in praying mantis (Tenodera aridifolia) with both scanning and transmission electron microscopes. We classified the sensilla into six types: chaetic, campaniform, coelocapitular, basiconic, trichoid and grooved peg sensilla, and inferred their presumptive functions on the basis of their external and internal structures. In addition, based on their distribution, we newly divided the flagellum into 6 distinct parts. This new division leads to a better understanding about the sexual dimorphism and the antennal development in the mantises. The sexual difference in distribution of the grooved peg sensilla suggests that this type of sensilla may play a role in sex-pheromone detection in mantis, which is a rare case of double walled sensilla mediating this function. PMID- 24231673 TI - Optimization of purification processes to remove polycyclic aromatic hydrocarbons (PAHs) in polluted raw fish oils. AB - Fish oils are one of the main sources of health promoting nutrients such as n-3 fatty acids in animal and human diet. Nevertheless, they could be an important source of persistent organic pollutants (POPs). Different strategies of decontamination processes to reduce polycyclic aromatic hydrocarbon (PAH) levels in fish oils, such as solvent extraction (ethanol) and adsorbent extraction using commercially available (activated carbon) and sustainable adsorbents (mussel shell and wood ashes), were compared. Adsorption conditions were evaluated and optimized by an experimental design and the experimental results were adjusted to response surfaces. In this way, PAH removals increased with increasing of individual PAH molecular weight and they range from 80% to 100% using activated carbon and from 10% to 100% using wood ashes. Pine wood ashes showed similar removal rates to activated carbon (87%-100%) excluding F (51%) and P (42%). No PAH removal was observed using mussel shell ashes. Ethanol extraction was also optimized and showed a good performance in the extraction of PAHs. However, it does affect their omega-3 fatty acid contents. Finally, real oil samples from different fishing areas: Spain, South America, and North Europe were selected for the decontamination experiments under experimental conditions previously optimized. PMID- 24231674 TI - Biophysical characteristics of cells cultured on cholesteryl ester liquid crystals. AB - This study aimed at examining the biophysical characteristics of human derived keratinocytes (HaCaT) cultured on cholesteryl ester liquid crystals (CELC). CELC was previously shown to improve sensitivity in sensing cell contractions. Characteristics of the cell integrin expressions and presence of extracellular matrix (ECM) proteins on the liquid crystals were interrogated using various immunocytochemical techniques. The investigation was followed by characterization of the chemical properties of the liquid crystals (LC) after immersion in cell culture media using Fourier transform infrared spectroscopy (FTIR). The surface morphology of cells adhered to the LC was studied using atomic force microscopy (AFM). Consistent with the expressions of the integrins alpha2, alpha3 and beta1, extracellular matrix proteins (laminin, collagen type IV and fibronectin) were found secreted by the HaCaT onto CELC and these proteins were also secreted by cells cultured on the glass substrates. FTIR analysis of the LC revealed the existence of spectrum assigned to cholesterol and ester moieties that are essential compounds for the metabolizing activities of keratinocytes. The immunostainings indicated that cell adhesion on the LC is mediated by self secreted ECM proteins. As revealed by the AFM imaging, the constraint in cell membrane spread on the LC leads to the increase in cell surface roughness and thickness of cell membrane. The biophysical expressions of cells on biocompatible CELC suggested that CELC could be a new class of biological relevant material. PMID- 24231675 TI - Qualitative characteristics of meat from young bulls fed different levels of crude glycerin. AB - The objective was to evaluate the fatty acid profile and qualitative characteristics of meat from young bulls fed crude glycerin. Forty-four animals with an initial live weight of 368 +/- 4 kg were used in a completely randomized design, with four treatments: no glycerin or addition of 6, 12 or 18% glycerin. The animals were slaughtered with 519.5 +/- 14.9 kg of live weight. The meat characteristics assessed were chemical composition, shear force, fatty acid concentration, color and lipid oxidation. The addition of glycerin increased the content of ether extract (P<0.05) in the muscle. A linear increase was observed (P<0.05) in the oleic acid contents (C18:1 cis 9). The saturated fatty acid (SFA) contents linearly decreased in the muscle as a function of glycerin addition. The lightness (L*) and yellowness (b*) indices increased with the use of crude glycerin (P<0.05). The crude glycerin increased the intramuscular fat and oleic acid content in the longissimus dorsi muscle. PMID- 24231676 TI - Lipid oxidation-induced oxidation in emu and ostrich myoglobins. AB - Emu and ostrich are ratites gaining increasing popularity as sources of low-fat meats. Secondary products of lipid oxidation, such as 4-hydroxy-2-nonenal (HNE), compromise myoglobin redox stability in a species-specific manner. However, the molecular basis of lipid oxidation-induced oxidation in ratite myoglobins has not been investigated. Therefore, our objective was to characterize lipid oxidation induced oxidation in ratite myoglobins, in comparison with beef myoglobin. At physiological condition (pH7.4, 37 degrees C) HNE accelerated (P<0.05) oxidation of emu, ostrich, and beef oxymyoglobins. Autoxidation and HNE-induced oxidation were greater (P<0.05) in ostrich oxymyoglobin than in emu and beef oxymyoglobins. Mass spectrometric analyses revealed that HNE formed mono-adduct with both emu and ostrich myoglobins after 6h of incubation. Tandem mass spectrometry demonstrated that HNE adducted histidine 36 in ostrich myoglobin, whereas histidines 34 and 36 were adducted in emu myoglobin. The results indicate that primary structure of ratite myoglobins influences their redox stability in the presence of prooxidants. PMID- 24231677 TI - Characterization and classification of Japanese consumer perceptions for beef tenderness using descriptive texture characteristics assessed by a trained sensory panel. AB - Meat tenderness is an important characteristic in terms of consumer preference and satisfaction. However, each consumer may have his/her own criteria to judge meat tenderness, because consumers are neither selected nor trained like an expert sensory panel. This study aimed to characterize consumer tenderness using descriptive texture profiles such as chewiness and hardness assessed by a trained panel. Longissimus muscles cooked at four different end-point temperatures were subjected to a trained sensory panel (n=18) and consumer (n=107) tenderness tests. Multiple regression analysis showed that consumer tenderness was characterized as 'low-chewiness and low hardness texture.' Subsequently, consumers were divided into two groups by cluster analysis according to tenderness perceptions in each participant, and the two groups were characterized as 'tenderness is mainly low-chewiness' and 'tenderness is mainly low-hardness' for tenderness perception, respectively. These results demonstrate objective characteristics and variability of consumer meat tenderness, and provide new information regarding the evaluation and management of meat tenderness for meat manufacturers. PMID- 24231679 TI - Roles of YB-1 under arsenite-induced stress: translational activation of HSP70 mRNA and control of the number of stress granules. AB - BACKGROUND: When cells become stressed, they form stress granules (SGs) and show an increase of the molecular chaperone HSP70. The translational regulator YB-1 is a component of SGs, but it is unclear whether it contributes to the translational induction of HSP70 mRNA. Here we examined the roles of YB-1 in SG assembly and translational regulation of HSP70 mRNA under arsenite-induced stress. METHOD: Using arsenite-treated NG108-15 cells, we examined whether YB-1 was included in SGs with GluR2 mRNA, a target of YB-1, and investigated the interaction of YB-1 with HSP70 mRNA and its effect on translation of the mRNA. We also investigated the distribution of these mRNAs to SGs or polysomes, and evaluated the role of YB 1 in SG assembly. RESULTS: Arsenite treatment reduced the translation level of GluR2 mRNA; concomitantly, YB-1-bound HSP70 mRNA was increased and its translation was induced. Sucrose gradient analysis revealed that the distribution of GluR2 mRNA was shifted from heavy-sedimenting to much lighter fractions, and also to SG-containing non-polysomal fractions. Conversely, HSP70 mRNA was shifted from the non-polysomal to polysome fractions. YB-1 depletion abrogated the arsenite-responsive activation of HSP70 synthesis, but SGs harboring both mRNAs were still assembled. The number of SGs was increased by YB-1 depletion and decreased by its overexpression. CONCLUSION: In arsenite-treated cells, YB-1 mediates the translational activation of HSP70 mRNA and also controls the number of SGs through inhibition of their assembly. GENERAL SIGNIFICANCE: Under stress conditions, YB-1 exerts simultaneous but opposing actions on the regulation of translation via SGs and polysomes. PMID- 24231678 TI - Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes. AB - Sensory organelle cilia have critical roles in mammalian embryonic development and tissue homeostasis. Intraflagellar transport (IFT) machinery is required for the assembly and maintenance of cilia. Yet, how this large complex passes through the size-dependent barrier at the ciliary base remains enigmatic. Here we report that FBF1, a highly conserved transition fibre protein, is required for the ciliary import of assembled IFT particles at the ciliary base. We cloned dyf-19, the Caenorhabditis elegans homologue of human FBF1, in a whole-genome screen for ciliogenesis mutants. DYF-19 localizes specifically to transition fibres and interacts directly with the IFT-B component DYF-11/IFT54. Although not a structural component of transition fibres, DYF-19 is required for the transit of assembled IFT particles through the ciliary base. Furthermore, we found that human FBF1 shares conserved localization and function with its worm counterpart. We conclude that FBF1 is a key functional transition fibre component that actively facilitates the ciliary entry of assembled IFT machinery. PMID- 24231681 TI - Acute and chronic effects of an aromatase inhibitor on pair-maintenance behavior of water-restricted zebra finch pairs. AB - Zebra finches are highly social songbirds that maintain life-long monogamous pair bonds. They rely heavily upon these pair-bonds to survive their ever-changing and unpredictable habitat in the Australian desert. These pair-bonds are maintained via a large repertoire of affiliative behaviors that for most of an individual's life are predominately associated with pair maintenance. Water restriction reduces circulating testosterone levels in male zebra finches and the size of the ovary and oviduct in female zebra finches, but water restriction has little or no effects on pair-maintenance behaviors and local levels of testosterone and estradiol in behaviorally-relevant brain regions. These data suggest that in water-restricted zebra finches, local synthesis of testosterone and estradiol in the brain may support the expression of pair-maintenance behaviors. Here, we directly test whether pair-maintenance behaviors are regulated by estradiol, acting via non-genomic or genomic mechanisms, in water-restricted (i.e., non breeding) zebra finches. In two experiments, subjects were treated with an aromatase inhibitor (fadrozole) either acutely or chronically, and a variety of pair-maintenance behaviors were quantified. Additionally, we quantified the effect of acute fadrozole treatment on brain and circulating estradiol and testosterone levels. Acute fadrozole administration rapidly decreased estradiol levels in the circulation and brain of males and also rapidly increased testosterone levels in the circulation and brain of both males and females. However, neither the acute nor chronic fadrozole treatment decreased pair maintenance behaviors. In one case, acute fadrozole treatment promoted affiliation. These data suggest that pair-maintenance behavior in non-breeding zebra finches is not promoted by estradiol acting via either non-genomic or genomic mechanisms. PMID- 24231680 TI - Canonical Wnt signaling differently modulates osteogenic differentiation of mesenchymal stem cells derived from bone marrow and from periodontal ligament under inflammatory conditions. AB - BACKGROUND: Cellular plasticity and complex functional requirements of the periodontal ligament (PDL) assume a local stem cell (SC) niche to maintain tissue homeostasis and repair. Here, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. As bone homeostasis is fundamentally controlled by Wnt-mediated signals, it was the aim of this study to characterize the SC-like capacities of cells derived from PDL and to investigate their involvement in bone pathophysiology especially regarding the canonical Wnt pathway. METHODS: PDLSCs were investigated for their SC characteristics via analysis of cell surface marker expression, colony forming unit efficiency, proliferation, osteogenic differentiation and adipogenic differentiation, and compared to bone marrow derived mesenchymal SCs (BMMSCs). To determine the impact of both inflammation and the canonical Wnt pathway on osteogenic differentiation, cells were challenged with TNF-alpha, maintained with or without Wnt3a or DKK-1 under osteogenic induction conditions and investigated for p-IkappaBalpha, p-NF-kappaB, p-Akt, beta-catenin, p-GSK-3beta, ALP and Runx2. RESULTS: PDLSCs exhibit weaker adipogenic and osteogenic differentiation capacities compared to BMMSCs. TNF-alpha inhibited osteogenic differentiation of PDLSCs more than BMMSCs mainly through regulating canonical Wnt pathway. Blocking the canonical Wnt pathway by DKK-1 reconstituted osteogenic differentiation of PDLSCs under inflammatory conditions, whereas activation by Wnt3a increased osteogenic differentiation of BMMSCs. CONCLUSIONS: Our results suggest a diverse regulation of the inhibitory effect of TNF-alpha in BMMSCs and PDLSCs via canonical Wnt pathway modulation. GENERAL SIGNIFICANCE: These findings provide novel insights on PDLSC SC-like capacities and their involvement in bone pathophysiology under the impact of the canonical Wnt pathway. PMID- 24231682 TI - Evolution of the gastrin-cholecystokinin gene family revealed by synteny analysis. AB - Gastrin (GAST) and cholecystokinin (CCK) are two structurally and functionally related peptide hormones that exert many functions, including regulation of gastric and pancreatic secretion, feeding behaviour and energy homeostasis. GAST and CCK genes are assumed to have diverged from a common ancestral gene, over 500 million years ago in the vertebrate lineage. However, although a large number of GAST and CCK-related sequences have been identified both in vertebrate and non vertebrate species, the evolutionary history of the GAST/CCK family remains little understood. To address this issue, we used extensive genome synteny comparisons of vertebrate chromosomes, in particular to evaluate the impact of whole-genome duplications. In the present study, we confirm that the GAST/CCK family in vertebrates is composed of two paralogous genes, namely GAST and CCK, and even three in teleosts, namely GAST, CCK1 and CCK2. We also show that the GAST and CCK genes arose by duplications of a single ancestral gene through the 2R and that the two copies of the CCK gene found in teleosts have probably been generated through the 3R. Finally, our results suggest that the vertebrate ancestor possessed four members of the GAST/CCK family, of which two have likely been lost during evolution. PMID- 24231683 TI - Easy hydrothermal preparation of Cu2ZnSnS4 (CZTS) nanoparticles for solar cell application. AB - CZTS nanoparticles were synthesized by a simple hydrothermal method at 230 degrees C for 24 h. The CZTS powder was synthesized with different concentration ratios of sulfur and copper, and the thin film was obtained by spin coating. A copper-rich concentration ratio of CZTS nanoparticles showed better results. The nanoparticles exhibited large absorption spectra, a fact linked to the quality of their optical properties. In addition, crystal structures, surface morphology, band gap, current-voltage, and Mott-Schottky diagram characterization of CZTS nanoparticles were also carried out by x-ray diffraction, Raman spectroscopy, scanning electron microscopy, energy-dispersive x-ray spectroscopy, transmission electron microscopy, ultraviolet-visible-near-infrared spectroscopy and photoelectrochemical measurements, respectively. PMID- 24231684 TI - The Uyo Trauma Registry-developed for sustainable audit of trauma care and cause in Nigeria. AB - The Cape Town Trauma Registry (CTTR) was developed as a minimum data set for low resource settings and was applied in a southern Nigerian tertiary hospital. Based on the outcome of the study, the CTTR was modified to produce the Uyo Trauma Registry. Using the CTTR, data was obtained prospectively from injured patients who presented to the Accident and Emergency Department of the University of Uyo Teaching Hospital over a 7 week period in June and July 2012. The final data set was determined based on the ease of capture of each item and its relative importance to injury surveillance. The goal for satisfactory data capture was chosen as >= 80%. The Uyo Trauma Registry has 19 patient-variable items and may be the first locally relevant hospital based injury surveillance tool in Nigeria. The Uyo Trauma Registry has provided the resource constrained setting in Nigeria with a simplified tool in order to sustainably obtain trauma data and thus engage in objective locally relevant efforts at injury prevention and improved care of the injured patient. PMID- 24231685 TI - Comments on 'novel multidrug therapy for disseminated rhinosporidiosis, refractory to dapsone - case report'. AB - Disseminated rhinosporidiosis can be successfully treated with multidrug therapy. Orally administered drugs can take longer to reach the affected areas in the presence of haemorrhage, oedema and inflammation. Wherever possible, surgical excision followed by drug therapy would be more effective. PMID- 24231686 TI - From the toe to the head: metastatic endophalmitis following staphylococcal purpura fulminans. AB - Staphylococcal infections may present in variable ways. Staphylococcal sepsis can cause significant morbidity and mortality. We report on the case of a 42-year-old man without any co-morbidities who presented with fever and purpura fulminans and later developed metastatic endophthalmitis. He was treated with intravenous and intravitreal vancomycin. The case is reported because of the rare co-occurrence of purpura fulminans and endophthalmitis. PMID- 24231687 TI - Brucellosis as an aetiology of septic arthritis. AB - Brucellosis is a zoonotic disease caused by a Gram-negative coccobacillus from the Brucella genus. The disease has a broad spectrum of clinical manifestations. The musculoskeletal system involvement is frequent and, rarely, arthritis can be the only clinical feature of the disease. We report a case of monoarthritis caused by Brucella melitensis. PMID- 24231688 TI - Relationships of individual, social, and physical environmental factors with older adults' television viewing time. AB - Sedentary behaviors (involving prolonged sitting) can be associated detrimentally with health outcomes. Older adults, the most sedentary age group, are especially at risk due to their high levels of television viewing time. This study examined individual, social, and physical environmental correlates of older adults' television viewing. Data on daily television viewing time, plus individual, social, and physical environmental factors were collected from 50,986 noninstitutionalized older adults (>= 65 years) in Flanders (Belgium). The results showed significant relationships between television viewing time and individual, social, and physical environmental factors. Subgroups at risk for high levels of television viewing were those who were functionally limited, less educated, widowed, and (semi)urban-dwelling older adults. Our findings illustrate a cross-sectional link between older adults' television viewing time and social composition of their neighborhood, formal participation, access to alternative activities, and safety from crime. PMID- 24231689 TI - Rh, Kell, Duffy, Kidd and Diego blood group system polymorphism in Brazilian Japanese descendants. AB - Polymorphisms of Rh, Kell, Duffy, Kidd and Diego blood group systems were studied in 209 unrelated Brazilian Japanese descendants from South of Brazil. The methods used were multiplex-PCR, AS-PCR and RFLP-PCR. The differences in frequencies among the populations were evaluated using chi-square test. The frequencies for Rh, Kell, Kidd and Diego system were similar to those of the Japanese. RHCE(*)CC, RHCE(*)EE genotypes and FY(*)01 allele were lower and FY(*)01N.01 was higher than Japanese. These differences in the frequencies between Brazilian Japanese descendants and Japanese could indicate a gene flow in Brazilian population and reinforce the importance of this knowledge to achieve safe red blood cells. PMID- 24231690 TI - Undifferentiated uterine sarcoma metastatic to the brain. AB - BACKGROUND: Undifferentiated uterine sarcoma (UUS) is a rare tumor with an aggressive growth pattern. They occur in women from 40 to 60 years and are generally characterized by poor prognosis, a high rate of local recurrence, and distant metastases. UUS accounts for 0.2% of all gynecological malignancies. Possible treatments include surgery, radiotherapy, and chemotherapy. CASE DESCRIPTION: A 65-year-old female with postmenopausal bleeding was found to have a uterine mass for which she underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The pathologic evaluation was consistent with undifferentiated endometrial sarcoma. She began experiencing headaches with associated visual disturbances. Magnetic resonance imaging (MRI) of the brain showed a homogenous enhancing occipital dural-based mass measuring 1.6 * 1.8 * 1.7 cm. Due to the rarity of metastatic uterine sarcoma to the brain, this was believed to represent a meningioma and subsequently observed. Interval MRI scan revealed a significant increase in size of the right occipital mass to 2.3 cm with increased edema and mass effect. She underwent right occipital image guided craniotomy for resection of the mass. Histopathology confirmed UUS metastases. CONCLUSION: Randomized trials analyzing these treatment options are limited due to the rarity of this disease; therefore, a standard therapy is not established. Based on a review of the literature, this is only the fourth case reported of UUS metastatic to the brain. PMID- 24231691 TI - Genotoxicity and antileishmanial activity evaluation of Physalis angulata concentrated ethanolic extract. AB - Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA) RESULTS: EEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000 MUg/plate and did not induce mutagenic effects after two oral administrations with a 24h interval at a dose level of 2000 mg/kg. EEPA presented antileishmanial activity and presented an IC50 value of 5.35 +/- 2.50 MUg/mL and 4.50 +/- 1.17 MUg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC50 of 6.14 +/- 0.59 MUg/mL. Importantly, the IC50 against L. amazonensis intracellular amastigotes was 1.23 +/- 0.11 MUg/mL. CONCLUSION: EEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites. PMID- 24231692 TI - Atomic configurations at InAs partial dislocation cores associated with Z-shape faulted dipoles. AB - The atomic arrangements of two types of InAs dislocation cores associated by a Z shape faulted dipole are observed directly by aberration-corrected high-angle annular-dark-field imaging. Single unpaired columns of different atoms in a matrix of dumbbells are clearly resolved, with observable variations of bonding lengths due to excess Coulomb force from bare ions at the dislocation core. The corresponding geometric phase analysis provides confirmation that the dislocation cores serve as origins of strain field inversion while stacking faults maintain the existing strain status. PMID- 24231693 TI - Life-threatening epistaxis and red blood cell polyagglutination under dabigatran. AB - Dabigatran is an oral thrombin inhibitor which has been approved for prevention of stroke or embolism in atrial fibrillation patients as an alternative to vitamin K antagonists. Dabigatran has been introduced into clinical practice, although issues like laboratory monitoring, its use in elderly patients, drug and food interactions, and an antidote have not been completely clarified. Severe epistaxis leading to haemorrhagic shock occurred in an 89-year-old woman with atrial fibrillation and moderate renal insufficiency after 10 months of dabigatran 110 mg/b.i.d. Correction of the anaemia with blood transfusions became difficult because it was impossible to assess her blood group due to polyagglutination. The indirect Coombs test was very highly +++ positive for IgG. Investigations about previous hospital admissions disclosed that in 2011, her blood group was 0 positive. The course was complicated by an erysipela of the right upper extremity, most probably induced by an infection through a venous catheter. An increase in the knowledge about potential side effects of dabigatran concerning infections and polyagglutination is urgently needed. PMID- 24231694 TI - Successful immune tolerance induction with a plasma-derived FVIII concentrate and intravenous immunoglobulins in a pediatric patient with congenital severe hemophilia A and poor prognostic factors. AB - We present the case of a pediatric patient born in July 1991, diagnosed with severe hemophilia A at 8 months of life after a hemarthrosis. He was treated with regular factor replacement therapy on-demand until an inhibitor was detected (1.75-2.5 BU) at the age of 6. The patient started an immunotolerance induction (ITI) program, which was discontinued 3 months later because of parental decision based on inhibitor persistence (3.75-6.75 BU). On-demand treatment with recombinant activated FVII in bleeding episodes was applied. Titer peaked 13 months later (37 BU). On May 2003 (age 11), rescue ITI with plasma-derived FVIII (Fanhdi, 100 IU/kg per 24 h daily) and intravenous immunoglobulin (IVIg) (Flebogamma, 1 g/kg per 24 h for 2 days every 3 weeks) was started. Inhibitor eradication was achieved after 16 months of ITI. The patient continued with FVIII+IVIg treatment for 3 additional months when he was switched to FVIII prophylaxis (40 IU/kg 3 times a week). At present, the patient is inhibitor-free. PMID- 24231695 TI - [Epigenetics as a novel therapeutic target of cancer]. AB - Epigenetic therapy is highly anticipated as a next player to molecular target drugs. Epigenetic abnormalities are maintained even after a somatic cell division, and can be causally involved in carcinogenesis. Recent cancer genome analysis revealed that a significant fraction of cancers cannot be accounted for only by mutations of known protein-coding genes, and that mutations of epigenetic genes are unexpectedly frequent. DNA demethylating drugs and histone deacetylase inhibitors are already approved, and many next-generation epigenetic drugs are under development. Application of epigenetic therapies to solid tumors is being attempted, and a promising result is available for non-small cell lung cancers. Right patients, right doses, and right combinations are key to further success, and can be done based on recent progresses in mechanistic analyses. PMID- 24231696 TI - [Environmental carcinogenic agents and cancer prevention: risk assessment and management]. AB - Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens. PMID- 24231697 TI - [Environmental air pollutants and the risk of cancer]. AB - The increased combustion of fossil fuels is one of the main reasons for the hazardous changes in the atmospheric composition. The sources of air pollution in urban areas include diesel motor vehicles, residential wood burning, and certain industrial processes. The types of air pollution include gases(eg, carbon monoxide, sulfur dioxide, nitrogen oxides, ozone)and suspended particulate matter(PM)such as PM2.5 and PM10 in diesel exhaust particles. PM2.5 refers to particles less than 2.5 micrometers in diameter. Long-term exposure to PM2.5 can increase the cardiovascular disease risk and lung cancer mortality. Although the role of PM2.5 in the etiology of lung cancer is not very clear, some researchers have shown evidence of increases in lung cancer mortality associated with exposure to PM2.5. Asbestos is also an important cause of cancer of the respiratory tract, particularly lung cancer and mesothelioma. The oncogenic hazards of asbestos fiber have been noted in cases of lowdose environmental exposure, as well in cases of high-dose occupational exposure. The use of asbestos has been strictly prohibited in Japan since 2006. However, large-scale natural disasters such as earthquakes, tsunamis, and typhoons can destroy many buildings and houses that were constructed before the ban on asbestos was initiated, thus resulting in the exposure of human beings to asbestos fibers. In the Cappadocian villages of Tuzkoy, Karain, and Sarihidir in Turkey, 50% of all deaths among villagers are caused by mesothelioma. This condition has been attributed to exposure to erionite, which is a type of fibrous zeolite mineral commonly found in this area of Turkey. However, pedigree studies of these villages showed that mesothelioma was prevalent in certain families but not in others, and that erionite exposure typically causes mesothelioma in those with a genetic predisposition to this disease. Recently, the germline BAP1 mutation was demonstrated in 2 different familial clusters of mesothelioma in the US. PMID- 24231698 TI - [Radiation carcinogenesis]. AB - Misrepair of DNA damage induced by ionizing radiation is a potential cause of carcinogenesis following exposure to radiation. Radiation exposure increases the incidence of the same types of mutations that occur spontaneously in a given population. A high incidence of DNA double-strand breaks is characteristic of damage by ionizing radiation compared with those induced by other environmental mutagens. In China, residents living in areas with high level background radiation(6mSv/y) had a significantly higher frequency of dicentric and ring chromosomes compared to that for the residents living in the control areas(2mSv/y). Radiation-associated increases in risk were seen for most sites. Gender-averaged excess absolute risk rates estimated at age 70, after exposure at age 30, differ in the sites, and the risks of gastric cancer, breast cancer, colon cancer, and lung cancer were highly increased, in that order. Latent periods for the development of leukemia and thyroid cancer after radiation exposure at ages younger than 18 were shorter compared to those for other solid cancers. PMID- 24231699 TI - [Cholangiocarcinoma developing in printing company workers: a new type of occupational cancer]. AB - The incidence of cholangiocarcinoma among the past or present workers in the department of offset color proof-printing at a printing company in Osaka was extremely high. The workers were relatively young and were exposed to several chemicals including organic solvents such as dichloromethane and 1,2 dichloropropane. Although the exact cause of cholangiocarcinoma in the patients remain unknown, it is likely that the development of cholangiocarcinoma was triggered during exposure to these chemicals. Some chemicals can act as environmental factors that lead to the development of cholangiocarcinoma. Therefore, we believe that cholangiocarcinoma is a new type of occupational cancer. PMID- 24231700 TI - [Studies on cases of spontaneous regression of cancer in Japan in 2011, and of hepatic carcinoma, lung cancer and pulmonary metastases in the world between 2006 and 2011]. AB - The PubMed and Ichushi databases were searched to identify cases of spontaneous regression of cancer that were featured in original papers and abstracts presented at conferences and these cases were examined. First,6 3 cases of spontaneous regression reported from Japan in 2011 were examined in detail. The most common types of cancer were lymphoma,hepatic carcinoma,and pulmonary cancer. The incidence of spontaneous regression was estimated at 1 per 12,000 patients with cancer and was calculated on the basis of the estimated number of patients who were newly diagnosed as having cancer during 1 year in Japan. Next, 83, 40,and 37 cases of spontaneous regression of hepatic carcinoma,pulmonary cancer,and lung metastases from primary malignant tumors,respectively,reported worldwide between 2006 and 2011, were analyzed. The cause of spontaneous regression in all 3 pathologies often involved an immunological mechanism. Other common factors that contributed to spontaneous regression were impaired tumor blood flow in patients with hepatic carcinoma,paraneoplastic syndrome in those with pulmonary cancer,and removal of the primary tumor in patients with lung metastasis. PMID- 24231701 TI - [Chemotherapy using gemcitabine hydrochloride for malignant lymphoma]. AB - This report summarizes the use of gemcitabine for the treatment of malignant lymphoma. Gemcitabine is a deoxycytidine antagonist that has characteristics different from those of the deoxycytidine antagonist cytarabine(Ara-C). International guidelines based on the results of recent clinical studies recommend the use of gemcitabine as monotherapy and in combination therapy, particularly for relapsed and refractory malignant lymphomas. Clinical studies on gemcitabine monotherapy up to 2012 reported response rates of 51-75% for peripheral T -cell lymphoma and cutaneous T-cell lymphoma. Regarding combination therapy, the GDP regimen consisting of gemcitabine, dexamethasone, and cisplatin was associated with response rates of 62-70% for relapsed or refractory Hodgkin lymphoma and 45-53% for relapsed or refractory non-Hodgkin lymphoma, thereby displaying comparable efficacy to existing salvage chemotherapy regimens. The GDP regimen has a favorable safety profile and is also associated with favorable autologous transplantation rates, which suggests its potential as induction chemotherapy before autologous transplantation. Concerning adverse reactions requiring clinical caution, lung disorder was reported in 8 of 27 patients(30%)who received a regimen of gemcitabine in combination with bleomycin. PMID- 24231702 TI - [Effect of radiotherapy and bisphosphonate on bone metastases from renal cell carcinoma]. AB - BACKGROUND: Bone metastases from renal cell carcinoma(RCC)are almost osteolytic and often cause pathological fractures. The objective of this study was to assess the efficacy of radiotherapy and zoledronic acid in patients with bone metastases from RCC. METHODS: We retrospectively analyzed 12 patients with bone metastases from RCC. Of these patients, 5 were treated with radiotherapy(RT group)and 7 were treated with a combination of radiotherapy and zoledronic acid(RT+Z group). We analyzed the radiological changes in the bone metastases and evaluated the response rate, survival rate, and skeletal-related event(SRE)rate. RESULTS: Radiologically, 2 patients showed progressive disease(PD), 3 showed stable disease( SD), 1 showed partial response(PR), and 1 showed complete response(CR)in the RT group(response rate: 28.6%). In the RT+Z group, 1 patient showed PD, 3 showed PR, and 1 showed CR(response rate: 80.0%). CONCLUSIONS: With regard to radiological changes, the response rate was higher in the RT group than in the RT+Z group, but the survival rate did not differ significantly between the 2 groups. SREs were less frequent in the RT+Z group than in the RT group. PMID- 24231703 TI - [A case of unresectable gastric cancer with poor ingestion]. AB - We encountered cases of unresectable gastric cancer in which patients had difficulty with ingestion because of pyloric stenosis and diffuse invasion. We examined the improvement in the quality of life(QOL)of patients and the effect and usefulness of S-1 treatment in such cases. The median survival time(MST; 310 days)of patients who received S-1 as primary treatment was significantly longer than that(105 days)of patients who did not receive S-1 treatment(p=0.0001). Of the 25 patients who underwent gastrojejunostomy, S-1 was administered to 10 patients(MST: 384 days). The MST of patients who received drugs other than S-1 was 121 days. Thus, the MST of patients who did receive S-1 was significantly longer than that of patients who did not receive S-1. In univariate analysis, oral ingestion, performance status(PS), best supportive care(BSC), and S-1 administration were prognostic factors. Of these factors, oral ingestion(p=0.0278, hazard ratio[HR]: 2.992)and S- 1 administration(p=0.0002, HR: 14.956)were prognostic factors in multivariate analysis. Gastrojejunostomy is desirable for the treatment of cases of unresectable gastric cancer with poor ingestion. In addition, the use of postoperative chemotherapy with S-1 alone or with S-1 as combination therapy may help improve prognosis. PMID- 24231704 TI - [Local injection of BRM-activated killer cells into an abdominal wall tumor]. AB - Based on the concept of living with cancer, wherein the goal is to help patients with highly advanced solid cancers maintain a high quality of life(QOL)without adverse events and drug resistance, we developed a new immunocyte therapy based on BRM-activated killer(BAK)cells, which are primarily CD56 positive lymphocytes. In a previous report, we documented the disappearance of liver metastases, as assessed by positron emission tomography-computed tomography(PET-CT), in patients with metastatic liver cancers into which BAK immunocytes had been administered via injection into the hepatic artery. Herein, upon the patient's request, we locally injected BAK lymphocytes into an abdominal tumor. In BAK therapy, 20 mL of peripheral blood are collected from a patient. Lymphocytes from this blood sample are subsequently activated and multiplied with immobilized anti-CD3 antibodies and IL-2 and are cultured for 2 weeks with E(bina)and serum-free ALys media to yield approximately 10 billion autologous lymphocytes. On the final day of incubation, the lymphocytes are treated with 1,000 units/mL of interferon(IFN) a for 15 minutes to enhance their therapeutic killing effects. During the second week, approximately 10 billion isolated autologous lymphocytes are suspended in 200 mL of Ringer's solution and are then drip-infused into the patient over a period of 1 hour. We injected approximately 10 billion BAK lymphocytes suspended in 50 mL of Ringer's solution into a 2-cm abdominal tumor in a single 60-year-old woman under ultrasonography guidance. This procedure was repeated every 3 weeks. After the third administration, we collected a biopsy specimen and examined it using PAS staining and microscopy. The 3 separate local injections of approximately 10 billion activated autologous lymphocytes each, primarily CD56 positive cells, into the tumor led to tumor fragmentation, leaving approximately 10 lymphocytes surrounding each cancer cell. These results suggest that BAK therapy is efficacious and show that locally administered BAK lymphocytes can reach cancer tissues and effectively kill cancer cells. PMID- 24231705 TI - [Effectiveness of intervention by the infection control team for cancer patients with a positive blood culture]. AB - Cancer patients at a high risk of acquiring infectious diseases should be maintained in a facility where good infection control practices are followed. At our hospital, the infection control team(ICT)provides expertise, education, and support to the staff, helping them maintain proper standards, thereby minimizing the risks of infection. The ICT(established in 2004)has implemented infection control programs by employing an appropriate number of staff members after the revision of medical treatment fees in 2011. Our intervention program includes 2 general policies, namely, ordering and collection of blood cultures and intervention for the medical care of patients with positive blood cultures. In this study, we evaluated the effectiveness of our intervention for cancer patients with a positive blood culture. During the surveillance period(April 2011 to July 2012), 42 positive cases were determined to be infectious. ICT intervention was required in 37 cases. Our suggestions were accepted in 92%(34/37)of the cases, and improved outcome was estimated in 65%(22/34)of the cases. The results of our study contribute to the scientific bases on which routine clinical practices could be promoted in the future. PMID- 24231706 TI - [The attempts and current status of cancer rehabilitation at Osaka Medical College Hospital]. AB - We introduced an attempt at cancer rehabilitation at Osaka Medical College Hospital. We also reported trends in the clinical department that ordered the cancer rehabilitation, and the days needed to consult the rehabilitation department after hospitalization for 1,028 patients who needed rehabilitation from January to June 2012. The number of rehabilitation orders for cancer patients has increased in comparison with the same period during 2009, and the percentage of cancer rehabilitation orders has also increased, both in total and in each clinical department consulted. In addition, clinical departments that introduced a rehabilitation schedule along with their treatments ordered cancer rehabilitations much earlier than those departments without such a schedule. In future, to start cancer rehabilitation at an earlier stage, we should endeavor to create awareness of the importance of cancer rehabilitation and the introduction of a rehabilitation schedule along with cancer treatments. PMID- 24231707 TI - [Two cases of recurrent invasive mucinous adenocarcinoma of the lung showing marked responses to platinum-based chemotherapyregimens with pemetrexed and bevacizumab]. AB - Here, we report 2 cases of recurrent invasive mucinous adenocarcinoma of the lung after surgery, which showed marked responses to platinum-based regimens with pemetrexed(PEM)and bevacizumab(BEV). The first patient was diagnosed with stage I B(p-T2N0M0)invasive mucinous adenocarcinoma, and new nodules were detected on computed tomography (CT)after 24 months of adjuvant chemotherapy with uracil/tegafur(UFT). Therefore, the patient was administered carboplatin(CBDCA; AUC 5.0), PEM(500mg/m2), and BEV(15mg/kg)for 6 courses followed by BEV(15mg/kg)for 3 courses, resulting in a complete response. The second patient was diagnosed with stage IV(p-T3N0M1)invasive mucinous adenocarcinoma, and metastases appeared after the surgery. The patient was treated with S-1 for 18 weeks, but the tumor recurred 18weeks after surgery. Therefore, the patient was administered 4 courses of cisplatin(CDDP 60mg/m2), PEM(500mg/m2), and BEV(15mg/kg)followed by 5 courses of PEM(15mg/kg)as maintenance therapy. This resulted in a good response. The first patient had grade 3 toxicities at the sixth course of combined CBDCA-PEM-BEV therapy, while the second patient did not have any adverse events throughout chemotherapy. These 2 cases showed that platinum-based regimens with PEM and BEV may be a good choice for patients with invasive mucinous adenocarcinoma of the lung. PMID- 24231708 TI - [Gemcitabine-induced tumor lysis syndrome caused by recurrent breast cancer in a patient without hemodialysis]. AB - Tumor lysis syndrome(TLS)induced by chemotherapy for solid tumors is rare. We report a case of a 59-year-old woman with breast cancer who developed TLS. She underwent surgery to treat breast cancer in 1992. 19 years after surgery, however, she was diagnosed with multiple bone metastases(disease free interval, 13 years and 3 months). In March 2011, gemcitabine regimen was initiated(1,250mg/m2, 14 days followed by a 7-day rest period)because of worsening of multiple bone metastases. The patient was immediately admitted and treated for suspected TLS when she presented at our hospital with symptoms such as depressed level of consciousness, serious anemia, hypercalcemia, hyperuricemia, and liver/renal dysfunction on day 16 of the first line of regimen. Rasburicase was found to be effective for hyperuricemia. PMID- 24231709 TI - [A case of locally advanced gastric cancer in which the patient underwent curative gastrectomy after treatment with systemic chemotherapy with bi-weekly s 1/docetaxel]. AB - Here, we report the case of a patient with advanced gastric cancer complicated by pyloric stenosis and direct invasion into the pancreas who underwent curative resection after bi-weekly S-1/docetaxel(DS)therapy after gastrojejunostomy. A 73 year-old man consulted a general practitioner because of indigestibility, and upper gastrointestinal endoscopy indicated gastric cancer. He was referred to our hospital. Gastric cancer, whole stomach tumor(LMU), 150*80 mm, Type 3, T4a(SE), N2, M0, stage III B was diagnosed, and surgery was performed. The tumor was seen to directly invade the pancreas and the middle colic artery intraoperatively, so only a gastrojejunostomy was performed. After the operation, the patient was treated with DS therapy for 13 courses, and the response was defined as non complete response(CR)and non-progressive disease (PD). During the second laparotomy, a curative operation was performed via distal gastrectomy because frozen-section diagnosis revealed that no cancer cells were present at the oral margin. Postoperatively, the tumor was diagnosed as LM, 10* 7 mm, 10*2.5 mm, pType 4, pT2(MP), pN0, pM0, CY0, stage I B. The patient is now receiving S-1 adjuvant chemotherapy and is still alive 2 years and 4 months after the first operation. PMID- 24231710 TI - [A case of advanced gastric cancer with regional lymph node metastasis showing pathological complete response after preoperative chemotherapy with docetaxel, cisplatin, and S-1]. AB - A 64-year-old man was diagnosed with advanced gastric cancer type 3 and regional celiac trunk lymph node metastases. We performed preoperative chemotherapy with docetaxel, cisplatin, and S-1(DCS therapy). Total gastrectomy with lymph node dissection was performed after 2 courses of DCS. Pathologically, no viable cells were found in the primary lesion or in the dissected lymph nodes. The pathological response to preoperative DCS therapy was classified as grade 3. The postoperative course was uneventful; the patient is currently healthy and receives periodic medical examinations. PMID- 24231711 TI - [A case of liver metastasis of primary duodenal cancer effectively treated with docetaxel therapy]. AB - A 75-year-old man who complained of upper abdominal discomfort was diagnosed with primary duodenal cancer. The patient was treated with a pancreaticoduodenectomy, ascending colectomy and postoperative chemotherapy of S-1 and irinotecan[IRIS; S 1, 80mg/m2(days 1-14); irinotecan, 100 mg/m2(days 1 and 15, every 4 weeks)]. However, after 4 IRIS cycles, computed tomography revealed a liver metastasis and massive ascites. The patient received second-line chemotherapy of tri-weekly docetaxel[60mg/m2,(day 1, every 3 weeks)]. After 2 cycles of docetaxel therapy, the liver tumor and ascites became undetectable. The patient was doing well 13 months after the operation. PMID- 24231712 TI - [A case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of extensive dissemination in advanced colon cancer, and the primary lesion could be resected]. AB - Here, we report a case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of a patient with unresectable advanced cecum cancer and carcinomatous peritonitis. A 52-year-old man was diagnosed with cecum cancer with extensive carcinomatous dissemination. He underwent open laparotomy, and the findings indicated a unresectable cecal tumor attached to the retroperitoneum; therefore, ileo-transverse colostomy was performed. After 6 courses of bevacizumab and XELOX therapy, the primary tumor as well as ascites and carcinomatous dissemination had disappeared, and a marked decrease in the serum carcinoembryonic antigen(CEA)level was noted. However, subsequently, positive emission tomography/computed tomography(PET/CT)indicated a recurrence of the primary tumor. Therefore, ileocecalectomy and D2 lymph node dissection were performed. Thus, we believe that bevacizumab/XELOX therapy may be useful as neoadjuvant chemotherapy for the treatment of advanced colon cancer with peritonitis carcinomatosa. PMID- 24231714 TI - [A case of unresectable multiple liver metastases of colorectal cancer in which ALTA(ZION), used to control internal hemorrhoidal bleeding, enabled administration of bevacizumab]. AB - Our patient was a 58-year-old woman with internal bleeding hemorrhoids who was undergoing FOLFOX6 treatment for unresectable multiple hepatic metastases of colorectal cancer. Response evaluation after 6 courses showed stable disease (SD), but side effects necessitated a change in regimen. Hemorrhoidal bleeding had also increased, and hemorrhoid-sclerosing therapy with ALTA(ZION)injections was administered. Because no bleeding was evident after treatment and the clinical course was uneventful, chemotherapy with bevacizumab was restarted. No hemorrhoidal bleeding occurred after bevacizumab administration, and the patient is currently continuing chemotherapy. In patients with advanced cancer who have bleeding internal hemorrhoids that cannot be controlled with conservative treatment, hemorrhoid-sclerosing therapy using ALTA appears to offer an effective treatment variation that enables the use of bevacizumab in cases with limited available therapeutic regimen options. PMID- 24231713 TI - [A case in which dihydropyrimidine dehydrogenase deficiency was strongly suspected during adjuvant chemotherapy with capecitabine for colon cancer]. AB - Severe toxicity in patients with a deficiency of dihydropyrimidine dehydrogenase(DPD), an enzyme that reduces fluoropyrimidine, is very rare, and reports on this condition are few. Accordingly, diagnosis is very difficult. The patient was 70-year-old man who was admitted for adjuvant chemotherapy with capecitabine(3,600mg/day)for rectal cancer. He was admitted to our hospital because of severe oral mucositis(grade 3)and hand-foot syndrome(grade 3). After hospitalization, he experienced complications with neutropenia(grade 4)and thrombocytopenia(grade 4). The patient died 25 days after the onset of chemotherapy. Despite the measurement of the DPD value in mononuclear cells of peripheral blood and urophanic uracil and dihydrouracil, we were unable to diagnose DPD deficiency. However, we suspected a partial deficiency of DPD on the basis of the clinical course. PMID- 24231715 TI - [Three cases of fatal thrombocytopenia after oxaliplatin-based chemotherapy]. AB - Oxaliplatin is a platinum salt that is particularly effective for treating gastrointestinal tumors. However, some reports state that oxaliplatin-based chemotherapy triggers fatal thrombocytopenia. Myelosuppression is recognized as the main cause of oxaliplatin-related thrombocytopenia, and other mechanisms for this side effect have been suggested, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. Other causes of thrombocytopenia such as thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura, heparin-induced thrombocytopenia, and pseudothrombocytopenia should also be considered. We encountered 3 patients who developed fatal thrombocytopenia after oxaliplatin based chemotherapy and describe the differential diagnosis of fatal thrombocytopenia here. PMID- 24231716 TI - [A case of hepatitis B virus reactivation in a patient with prior resolved hepatitis B infection during bevacizumab plus FOLFIRI treatment]. AB - Hepatitis Bvirus (HBV)reactivation induced by cancer chemotherapy is increasingly being observed. However, most reports of resolved HBV[hepatitis Bsurface antigen(HBs-Ag)negative and hepatitis Bsurface antibody(HBs-Ab)positive and/or hepatitis Bcore antibody(HBc-Ab)positive]infection involve patients with hematological malignancies, whereas few describe patients with solid cancers. In this study, we report our experience with a patient with resolved HBV infection who was undergoing bevacizumab plus FOLFIRI treatment for rectal cancer when HBV reactivation was noted. This 74-year-old man was HBs-Ag negative, HBs-Ab negative, HBcAb positive, hepatitis B e antigen(HBe-Ag)negative, and hepatitis Be antibody(HBe-Ab)negative and had HBV-DNA levels below the detection limit. Forty two days after the 21st cycle of bevacizumab plus FOLFIRI treatment, his aspartate aminotransferase and alanine aminotransferase levels increased. At followup examination, he was HBs-Ag positive, HBs-Ab negative, HBc-Ab positive, HBe-Ag positive, and HBe-Ab positive, while his HBV-DNA levels had increased to>9.0 log copies/mL, confirming HBV reactivation. His treatment included entecavir(0.5mg/ day)administration and plasmapheresis, but he succumbed to liver failure 82 days after his final dose of bevacizumab plus FOLFIRI. Thus, HBV reactivation can occur during bevacizumab plus FOLFIRI treatment in rectal cancer patients with a resolved prior HBV infection. No similar report has been published to date, and we believe that this study will be important when discussing HBV reactivation in patients with resolved HBV infection. Future studies will require detailed investigations in a larger number of institutions. PMID- 24231717 TI - How is the increased risk of colorectal cancer in first-degree relatives of patients communicated? AB - OBJECTIVES: Compared with the general population, first-degree relatives (FDRs) of colorectal cancer (CRC) patients have a two-fold to four-fold higher risk of developing CRC. Little data is available regarding communication between doctors and CRC patients about risk to FDRs. We aimed to evaluate CRC patients' knowledge of FDRs' increased CRC risk, and FDRs' knowledge of this risk and adherence to CRC screening. MATERIALS AND METHODS: In this retrospective, single-center, population-based observational study, patients aged 18-80 years who underwent surgery for CRC between January 2005 and May 2010 were asked to complete a questionnaire. A questionnaire sent to the patients' FDRs (siblings and children) asked whether they had been advised to undergo any CRC screening examination, whether they had done so, and if so, when initiated and by whom. Main outcome measurements were: CRC patients' and their FDRs' information status regarding the FDRs' increased CRC risk and screening status. RESULTS: Of 343 index patients (390 contacted, 47 deceased/moved), 134 replied to the survey (39.1% response rate). Among index patients, 82.1% (110/134) were informed about FDRs' increased CRC risk. This information was provided mainly by gastroenterologists and general practitioners (65.7 and 28.4%, respectively). Among FDRs, 85.1% (143/168) were informed about their increased CRC risk, but 69% did not undergo a screening colonoscopy. Among the FDRs more than 50 years of age, 40.8% did not undergo a screening colonoscopy. CONCLUSION: In Switzerland, CRC patients and their FDRs are well informed about FDRs' increased CRC risk. However, the majority of FDRs do not undergo the recommended CRC screening. PMID- 24231718 TI - Spectrum of mutations associated with methionine adenosyltransferase I/III deficiency among individuals identified during newborn screening in Japan. AB - Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 and 2012 in Hokkaido, Japan, the estimated incidence of MAT I/III deficiency was 1 in 107,850. 24 patients (13 males, 11 females) from 11 prefectures in Japan were referred to our laboratory for genetic diagnosis of MAT I/III deficiency. They were all found between 1992 and 2012 by the NBS program in each region. In these 24 individuals, we identified 12 distinct mutations; 14 patients were heterozygous for an R264H mutation; R264H caused an autosomal dominant and clinically benign phenotype in each case. The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. Putative amino acid substitutions at R356 were observed with six alleles (three R356P, two R356Q, and one R356L). MAT I/III deficiency is not always benign because three of our cases involved brain demyelination or neurological complications. DNA testing early in life is recommended to prevent potential detrimental neurological manifestations. PMID- 24231719 TI - Elevated red blood cell distribution width and inflammation in printing workers. AB - BACKGROUND: The aim of this study was to estimate the effects of exposure to chemical compounds on systemic biochemical inflammatory markers in printing industry workers. MATERIAL/METHODS: Fifty-eight printing workers from 19 different small- and medium-sized enterprises in the printing sector were investigated. For comparison, 80 healthy workers not subjected to workplace chemicals served as control subjects. RESULTS: No significant differences were observed between the printing workers and control subjects with respect to age, BMI, waist circumference/hip circumference ratio, smoking, and alcohol consumption. Printing workers had significantly higher serum TNF-alpha levels (11.02 +/- 5.34 vs. 9.26 +/- 3.87 pg/ml, p=0.039), plasma fibrinogen levels (1.74 +/- 0.49 vs. 1.38 +/- 0.5 mg/dl, p=0.012), and red blood cell distribution width (RDW-SD) (49.77 +/- 3.09 vs. 47.3 +/- 2.88 p<0.01) compared to control subjects. CONCLUSIONS: Elevation of RDW, serum TNF-alpha, and plasma fibrinogen levels in printing workers may be due to systemic toxic effects of chemical compounds used in this sector. TNF-alpha is an inflammatory cytokine that has a wide spectrum of biological activities, and fibrinogen plays an important role in pathological processes. Some compounds may be carcinogenic or mutagenic. Better designed workplaces and working conditions will help to reduce the hazardous effects of chemical compounds. PMID- 24231721 TI - The two faces of generalism. PMID- 24231720 TI - Vagal afferents mediate antinociception of estrogen in a rat model of visceral pain: the involvement of intestinal mucosal mast cells and 5-hydroxytryptamine 3 signaling. AB - Estrogen reportedly facilitates visceral nociception at the spinal or supraspinal level. The present study was aimed to investigate whether estrogen modulates visceral pain through the vagal pathway. Ovariectomized rats received estradiol, which was administered subcutaneously (to act through both the vagal and spinal pathways) or intraduodenally (to preferentially act through the vagal pathway). Luminally applied estradiol induced a rapid and significant decrease in the visceromotor response to colorectal distension, with increased c-Fos expression in nodose ganglion neurons. Systemically injected estradiol increased visceromotor response and c-Fos expression in both nodose and dorsal root ganglion (T6-12) neurons. The antinociceptive effect of estrogen was abolished by surgical vagotomy or chemical denervation of vagal afferents. Both luminally and systemically administered estradiol elicited selective 5-hydroxytryptamine secretion from the duodenum. Granisetron, a 5-hydroxytryptamine 3 receptor antagonist, reversed the antinociceptive effect of estrogen. Intestinal mucosal mast cell stabilizers prevented estradiol-induced antinociception and 5 hydroxytryptamine secretion. Ultrastructural analysis revealed that estradiol caused piecemeal degranulation of intestinal mucosal mast cells. The actions of estradiol were inhibited by an estrogen receptor beta antagonist and mimicked by an estrogen receptor beta agonist. These results suggest that estrogen can trigger vagus-mediated antinociception, which is masked by its spinally mediated pronociception. PERSPECTIVE: This study is the first to show a vagus-mediated estrogenic antinociception, in which the nongenomic estrogen receptor beta mediated, intestinal mucosal mast cell-derived 5-hydroxytryptamine/5 hydroxytryptamine 3 receptor pathway is involved. This work may provide new insights into the sex hormone modulation of visceral sensitivity related to irritable bowel syndrome and indicate potential therapeutic targets to manage this disease. PMID- 24231722 TI - Opportunities outside the traditional role of individuals with an educational background in Nuclear Medicine Technology and a bachelor's degree. PMID- 24231723 TI - Intraoperative injection of radiocolloid for sentinel node biopsy in breast cancer. AB - Preoperative injection of radiocolloid for axillary sentinel node biopsy in breast cancer is uncomfortable for patients. This study evaluated the reliability of radiocolloid injection as determined by sentinel node identification rate and positive sentinel node biopsy rate, after the patient has been anesthetized in the operating room as compared with preoperative injection. METHODS: After institutional review board approval, a retrospective cohort of patients with breast cancer who underwent sentinel node biopsy from January 2005 through December 2010 was evaluated for analysis. Patients who received intraoperative injection of radiocolloid were compared with those who received their injection preoperatively. Patients with incomplete pathologic staging or having received neoadjuvant chemotherapy were excluded. All patients received radiocolloid injections into the retroareolar tissue; some also received intradermal injection directly over the tumor. All injections contained 37 MBq (1 mCi) in 0.5 mL of filtered (0.22-MUm) (99m)Tc-sulfur colloid. RESULTS: Over the 6-y study period there were 904 sentinel node biopsy procedures, and 165 patients were excluded from analysis. Of the 739 sentinel node biopsies that were analyzed, 647 had preoperative injection of radiocolloid and 92 had intraoperative injection. The overall sentinel lymph node identification rates were similar for the 2 groups: 93.5% for the preoperative injection group and 94.6% for the intraoperative injection group (not statistically significant). The identification rates remained comparable for both groups when analyzed by T stage of the tumor. The average number of sentinel lymph nodes removed was similar between preoperative and intraoperative injection: 2.60 and 2.70 nodes, respectively. The overall rates of positive sentinel nodes were comparable for the 2 groups: 25.6% for the preoperative injection group and 26.4% for the intraoperative injection group (not statistically significant). When analyzed by T stage, the positive sentinel node rates remained similar between the 2 groups. CONCLUSION: The sentinel lymph node identification rate of 94.6% for the intraoperative injection group was similar to other published sentinel lymph node identification rates (96%-100%). The positive sentinel lymph node rate was also comparable to that of published series. Intraoperative injection of radiocolloid for axillary sentinel node biopsy appears equivalent to preoperative injection and is a less painful experience for breast cancer patients. PMID- 24231724 TI - Role of hypothalamic neurogenesis in feeding regulation. AB - The recently described generation of new neurons in the adult hypothalamus, the center for energy regulation, suggests that hypothalamic neurogenesis is a crucial part of the mechanisms that regulate food intake. Accordingly, neurogenesis in both the adult and embryonic hypothalamus is affected by nutritional cues and metabolic disorders such as obesity, with consequent effects on energy-balance. This review critically discusses recent findings on the contribution of adult hypothalamic neurogenesis to feeding regulation, the impact of energy-balance disorders on adult hypothalamic neurogenesis, and the influence of embryonic hypothalamic neurogenesis upon feeding regulation in the adult. Understanding how hypothalamic neurogenesis contributes to food intake control will change the paradigm on how we perceive energy-balance regulation. PMID- 24231726 TI - A coordinated comprehensive professional development training's effect on summer day camp staff healthy eating and physical activity promoting behaviors. AB - BACKGROUND: The YMCA of USA recently adopted Healthy Eating and Physical Activity (HEPA) Standards for their summer-day- camps (SDCs). Standards call for staff to exhibit HEPA promoting behaviors while eliminating HEPA discouraging behaviors. No studies have evaluated training programs to influence policy specified staff behaviors and related changes in child activity in SDCs. METHOD: Four YMCA SDCs serving approximately 800 children/week participated in this no control group pre/post pilot study. Professional development training founded in the 5 Ms (Mission, Model, Manage, Monitor, Maximize) and LET US Play principles (lines; elimination; team size; uninvolved staff/kids; and space, equipment, and rules) was delivered to staff. Outcomes were staff promotion behaviors and child activity assessed via systematic observation instruments. RESULTS: Twelve of 17 HEPA staff behaviors changed in the appropriate direction from baseline to postassessment with 5 behaviors reaching statistically significant changes. The percentage of girls and boys observed in moderate-to-vigorous physical activity increased from 15.3% to 18.3% (P > .05) and 17.9% to 21.2%, whereas sedentary behavior decreased from 66.8% to 59.8% and 62.3% to 53.6%, respectively. CONCLUSION: Evidence suggests that the professional development training designed to assist SDCs to meet the HEPA Standards can lead to important changes in staff behaviors and children's physical activity. PMID- 24231725 TI - Cyclic AMP sensor EPAC proteins and energy homeostasis. AB - The pleiotropic second-messenger cAMP plays a crucial role in mediating the effects of various hormones on metabolism. The major intracellular functions of cAMP are transduced by protein kinase A (PKA) and by exchange proteins directly activated by cAMP (EPACs). The latter act as guanine-nucleotide exchange factors for the RAS-like small G proteins Rap1 and Rap2. Although the role of PKA in regulating energy balance has been extensively studied, the impact of EPACs remains relatively enigmatic. This review summarizes recent genetic and pharmacological studies concerning EPAC involvement in glucose homeostasis and energy balance via the regulation of leptin and insulin signaling pathways. In addition, the development of small-molecule EPAC-specific modulators and their therapeutic potential for the treatment of diabetes and obesity are discussed. PMID- 24231727 TI - A nonspecific defensive compound evolves into a competition avoidance cue and a female sex pheromone. AB - The evolution of chemical communication and the origin of pheromones are among the most challenging issues in chemical ecology. Current theory predicts that chemical communication can arise from compounds primarily evolved for non communicative purposes but experimental evidence showing a gradual evolution of non-informative compounds into cues and true signals is scarce. Here we report that females of the parasitic wasp Leptopilina heterotoma use the defensive compound (-)-iridomyrmecin as a semiochemical cue to avoid interference with con- and heterospecific competitors and as the main component of a species-specific sex pheromone. Although competition avoidance is mediated by (-)-iridomyrmecin alone, several structurally related minor compounds are necessary for reliable mate attraction and recognition. Our findings provide insights into the evolution of insect pheromones by demonstrating that the increasing specificity of chemical information is accompanied by an increasing complexity of the chemical messengers involved and the evolution of the chemosensory adaptations for their exploitation. PMID- 24231728 TI - The use of local concentrated heat versus topical acyclovir for a herpes labialis outbreak: results of a pilot study under real life conditions. AB - BACKGROUND: Frequent outbreak of herpes labialis can affect quality of life by prodromes like burning, itching, and swelling. Topical applied preparations aim to shorten the duration of symptoms, inhibit the virus replication and/or accelerate the healing process. Local concentrated heat (LCH) can reduce burning, itching, or swelling of the skin by influence of mechano-heat sensitive afferent neurons. PATIENTS AND METHODS: To examine the effectiveness of two different topical applications (LCH versus topical acyclovir [TACV]) under real life conditions, we conducted a prospective, observational, reference-controlled cohort pilot study with 103 patients. Occurrence of prodromal burning, itching, swelling, and quality of life were assessed. RESULTS: The LCH observation group (OG) showed a significantly faster improvement in all symptoms after 1-day of application than the TACV OG. The burden and duration of disease was lower and shorter in the LCH OG than in the TACV OG. CONCLUSIONS: The prodromal symptoms in recurrent herpes labialis were attenuated more effectively by LCH than by TACV. PMID- 24231730 TI - Autophagy as a mechanism of antiviral defense at the maternal-fetal interface. AB - Mechanisms to protect against viral infections are crucial during pregnancy as maternal-fetal transmission can have serious pathological outcomes, including fetal infection and its sequelae, such as growth restriction, birth defects, and/or fetal death. The trophoblast forms the interface between the feto placental unit and the maternal blood, and is therefore a critical physical and immunological barrier to restrict the spread of pathogens into the fetal microenvironment. Recently, we found that primary human placental trophoblast (PHT) cells are highly resistant to infection by diverse viruses. In this study, we also found that conditioned medium from PHT cell cultures transferred viral resistance to nonplacental recipient cells, suggesting that a component secreted by trophoblasts and present within the conditioned medium is responsible for this antiviral effect. We found that specific miRNAs from a unique primate- and placental-specific locus?the C19MC (chromosome 19 miRNA cluster)?are packaged within exosomes produced by PHT cells and confer viral resistance in nonplacental recipient cells. In addition to conveying viral resistance, we found that PHT derived exosomes and select miRNA members of the C19MC family strongly induce autophagy, which is involved in recipient cell viral resistance. Our findings establish an exciting and novel mechanism by which placental trophoblasts exploit exosome-dependent transfer of placental-specific miRNAs to influence autophagic induction and antiviral immunity at the maternal?fetal interface. PMID- 24231729 TI - mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions. AB - Pancreatic cancer is characterized by near-universal mutations in KRAS. The mammalian target of rapamycin (mTOR), which functions downstream of RAS, has divergent effects on stem cells. In the present study, we investigated the significance of the mTOR pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133(+) pancreatic cancer cells and sphere formation which is an index of self renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Further, rapamycin had different effects on CD133(+) cells compared to cyclopamine which is an inhibitor of the Hedgehog pathway. Thus, the mTOR pathway has a distinct role although both pathways maintain pancreatic cancer stem cells. Therefore, mTOR might be a promising target to eliminate pancreatic cancer stem cells. PMID- 24231731 TI - Thermoelectric power factor of ternary single-crystalline Sb2Te3- and Bi2Te3 based nanowires. AB - Nanowires of bismuth antimony telluride and bismuth telluride selenide (Bi15Sb29Te56 and Bi38Te55Se7) were grown by template-based pulsed electrodeposition. The composition and the crystallinity of the nanowires were determined by high-resolution transmission electron microscopy. The thermoelectric properties (Seebeck coefficient and electrical conductivity) of single p- and n-type nanowires, with diameter 80 nm and 200 nm, respectively, were determined as a function of temperature before and during heating in a helium atmosphere up to 300 K along the growth direction of the nanowires. After additional annealing in a tellurium atmosphere at 525 K, significantly enhanced transport properties are observed. Bulk-like power factors are achieved. In Bi38Te55Se7 nanowires, the Seebeck coefficients increase to -115 MUV K(-1) and the thermoelectric power factors increase to 2820 MUW K(-2) m(-1) at room temperature. In Bi15Sb29Te56 nanowires, Seebeck coefficients of up to S = +156 MUV K(-1) and power factors of up to 1750 MUW K(-2) m(-1) are obtained at room temperature. PMID- 24231732 TI - Neuroprotective effect of geraniol and curcumin in an acrylamide model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy. AB - Chronic exposure of acrylamide (ACR) leads to neuronal damage in both experimental animals and humans. The primary focus of this study was to assess the ameliorative effect of geraniol, (a natural monoterpene) against ACR-induced oxidative stress, mitochondrial dysfunction and neurotoxicity in a Drosophila model and compare its efficacy to that of curcumin, a spice active principle with pleiotropic biological activity. Adult male flies (8-10 days) were exposed (7 days) to ACR (5 mM) with or without geraniol and curcumin (5-10 MUM) in the medium. Both phytoconstituents significantly reduced the incidence of ACR-induced mortality, rescued the locomotor phenotype and alleviated the enhanced levels of oxidative stress markers in head/body regions. The levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ACR exposure was also restored with concomitant elevation in the activities of detoxifying enzymes. Interestingly, ACR induced mitochondrial dysfunctions (MTT reduction, activities of SDH and citrate synthase enzymes) were alleviated by both phytoconstituents. While ACR elevated the activity of acetylcholinesterase in head/body regions, marked diminution in enzyme activity ensued with co-exposure to phytoconstituents suggesting their potency to mitigate cholinergic function. Furthermore, phytoconstituents also restored the dopamine levels in head/body regions. The neuroprotective effect of geraniol was comparable to curcumin in terms of phenotypic and biochemical markers. Based on our evidences in fly model we hypothesise that geraniol possess significant neuromodulatory propensity and may be exploited for therapeutic application in human pathophysiology associated with neuropathy. However, the precise mechanism/s by which geraniol offers neuroprotection needs to be investigated in appropriate neuronal cell models. PMID- 24231733 TI - Saline-assisted aspirations for collecting synovial fluid from noneffused knees: technique and validation. AB - CONTEXT: To better understand why a knee develops osteoarthritis after joint trauma we need to assess the local biochemical changes. Unfortunately, it is challenging to obtain synovial fluid from a knee with no effusion. OBJECTIVE: To describe the authors' protocol for aspirating synovial fluid from noneffused knees. Second, they demonstrate the validity of this method by evaluating the relationships between normalized and raw biomarker concentrations among knees with effusion (undergoing a traditional aspiration) and without effusion (requiring a saline-assisted aspiration). DESIGN: Validation study based on secondary analyses from 2 cohort studies. SETTING: Outpatient orthopedic clinic and basic-science laboratory. PARTICIPANTS: Participants had moderate to severe radiographic knee osteoarthritis (n = 15 with and 11 without effusion) and no osteoarthritis or effusion (n = 4). INTERVENTIONS: The same orthopedic surgeon performed all synovial-fluid joint aspirations, including saline-assisted aspirations. MAIN OUTCOME MEASURES: The authors used multiplex enzyme-linked immunosorbent assays to determine 7 synovial-fluid biomarker concentrations. They then calculated correlations between raw and normalized (to total synovial-fluid protein content) biomarker concentrations. RESULTS: The authors excluded 1 sample collected with a saline-assisted aspiration because it contained blood. Normalized biomarker concentrations had positive associations with raw biomarker concentrations (r = .77-.99), with the exception of interleukin-13 and interleukin-1beta among knees that underwent a saline-assisted aspiration. Excluding interleukin-1beta, associations between normalized and raw biomarker concentrations were consistent between knees that had a saline-assisted or traditional aspiration. CONCLUSIONS: Saline-assisted aspiration is a valid technique for assessing the local biochemical changes in knees without effusion. PMID- 24231734 TI - Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice. AB - Social isolation during the vulnerable period of adolescence produces emotional dysregulation manifested by abnormalities in adult behaviors that require emotional processing. The affected brain regions may include the basolateral amygdala (BLA), where plasticity of glutamatergic synapses in principal neurons plays a role in conditioned emotional responses. This plasticity is dependent on NMDA receptor trafficking denoted by intracellular mobilization of the obligatory NR1 NMDA subunit. We tested the hypothesis that the psychosocial stress of adolescent social isolation (ASI) produces a lasting change in NMDA receptor distribution in principal neurons in the BLA of adults that express maladaptive emotional responses to sensory cues. For this, we used behavioral testing and dual electron microscopic immunolabeling of NR1 and calcium calmodulin-dependent protein kinase II (CaMKII), a protein predominantly expressed in principal neurons of the BLA in adult C57Bl/6 mice housed in isolation or in social groups from post-weaning day 22 until adulthood (~3 months of age). The isolates showed persistent deficits in sensorimotor gating evidenced by altered prepulse inhibition (PPI) of acoustic startle and hyperlocomotor activity in a novel environment. Immunogold-silver labeling for NR1 alone or together with CaMKII was seen in many somatodendritic profiles in the BLA of all mice irrespective of rearing conditions. However, isolates compared with group-reared mice had a significantly lower cytoplasmic (4.72 +/- 0.517 vs 6.31 +/- 0.517) and higher plasmalemmal (0.397 +/- 0.0779 vs 0.216 +/- 0.026) density of NR1 immunogold particles in CaMKII-containing dendritic spines. There was no rearing-dependent difference in the size or number of these spines or those of other dendritic profiles within the neuropil, which also failed to show an impact of ASI on NR1 immunogold labeling. These results provide the first evidence that ASI enhances the surface trafficking of NMDA receptors in dendritic spines of principal neurons in the BLA of adult mice showing maladaptive behaviors that are consistent with emotional dysregulation. PMID- 24231736 TI - Chordin expression in the adult rat brain. AB - Bone morphogenetic proteins (BMPs) exert its biological functions by interacting with membrane bound receptors. However, functions of BMPs are also regulated in the extracellular space by secreted antagonistic regulators. Chordin is an extracellular BMP antagonist that binds BMP-2, 4, and 7 with high affinity and thus interferes with binding to BMP receptors. Although chordin expression has been well described in the early development of the CNS, little information is available for its expression in the adult CNS. We, thus, investigated chordin expression in the adult rat CNS using immunohistochemistry. Chordin was intensely expressed in most neurons, and their dendrites and axons. In addition, abundant chordin expression was also observed in the neuropil of the gray matters where high plasticity is reported, such as the molecular layer of the cerebellum and the superficial layer of the superior colliculus. Furthermore, we found that astrocytes and ependymal cells also express chordin protein. These data indicate that chordin is more widely expressed throughout the adult CNS than previously reported, and its continued abundant expression in the adult brain strongly supports the idea that chordin plays pivotal roles also in the adult brain. PMID- 24231735 TI - White matter astrocytes in health and disease. AB - Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and the oligodendrocytes. Astrocytes have an important part in facilitating myelination in the CNS, however, comparatively less is known about how they affect myelination. This review therefore summarizes the literature and explores lingering questions surrounding differences between white matter and gray matter astrocytes, how astrocytes support myelination, how their dysfunction in pathological states contributes to myelin pathologies and how astrocytes may facilitate remyelination. We discuss how astrocytes in the white matter are specialized to promote myelination and myelin maintenance by clearance of extracellular ions and neurotransmitters and by secretion of pro myelinating factors. Additionally, astrocyte-oligodendrocyte coupling via gap junctions is crucial for both myelin formation and maintenance, due to K(+) buffering and possibly metabolic support for oligodendrocytes via the panglial syncytium. Dysfunctional astrocytes aberrantly affect oligodendrocytes, as exemplified by a number of leukodystrophies in which astrocytic pathology is known as the direct cause of myelin pathology. Conversely, in primary demyelinating diseases, such as multiple sclerosis, astrocytes may facilitate remyelination. We suggest that specific manipulation of astrocytes could help prevent myelin pathologies and successfully restore myelin sheaths after demyelination. PMID- 24231737 TI - The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse. AB - Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 MUM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5 HT neurons via the activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents. PMID- 24231738 TI - D1-dopamine and alpha1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex. AB - Functional interactions between dopaminergic and noradrenergic systems occur in many brain areas, including the prefrontal cortex (PFC). Biochemical, electrophysiological and behavioral data indicate crosstalk between D1 dopamine receptor (D1R) and alpha1-adrenergic receptor (alpha1AR) signaling in the PFC. However, it is unknown whether these interactions occur within the same neurons, or between neurons expressing either receptor. In this study, we used electron microscopy immunocytochemistry to demonstrate that D1Rs and alpha1ARs co-localize in rat PFC neuronal elements, most prominently in dendrites (60-70%), but also significantly in axon terminals, unmyelinated axons and spines (~20-30%). Our data also showed that the ratio of plasma membrane-bound to intracellular alpha1ARs is significantly reduced in D1R-expressing dendrites. Similar results were obtained using either a pan-alpha1AR or a selective alpha1bAR antibody to label noradrenergic receptors. Thus, these results demonstrate that D1Rs and alpha1ARs co-localize in PFC dendrites, thereby suggesting that the catecholaminergic effects on PFC function may be driven, at least in part, by cell-autonomous D1R-alpha1AR interactions. PMID- 24231739 TI - NAC1, A POZ/BTB protein interacts with Parkin and may contribute to Parkinson's disease. AB - Loss-of-function in the Parkin protein is thought to play a part in causing neuronal cell death in patients with Parkinson's disease. This study explores the effect of Parkin degradation, via the overexpression of nucleus accumbens 1 (NAC1), on cell viability. It was found that NAC1 and Parkin are co-localized within the cell and interact with one another, leading to a decrease in Parkin levels. Moreover, NAC1 down-regulates Parkin by presenting it for ubiquitin dependent proteasome degradation, which causes a decrease in proteasomal activity in neuronal cells. Consequently, this decrease in proteasomal activity leads to an increase in the cells' susceptibility to proteasome inhibition-induced toxicity. It was also found that Parkin and NAC1 are key proteins found to be present mainly in the cytoplasm and are co-localized in neurons of Parkinson's disease patients. Interestingly, mutation in the POZ/BTB domain (Q23L) of NAC1 disrupts the co-localization and interaction of NAC1 with Parkin and it further abrogates the proteasome inhibition-induced toxicity. We further observed that co transfection of the mutant form of NAC1 with Parkin reversed the proteasome activity and 20S proteasome protein levels. These results indicate a novel interaction between NAC1 and Parkin that leads to neuronal cell death, a main characteristic in Parkinson's disease. PMID- 24231741 TI - Lysozyme-stabilized gold nanoclusters as a novel fluorescence probe for cyanide recognition. AB - Lysozyme-stabilized gold nanoclusters (Lys-AuNCs) have been synthesized and utilized as a fluorescent probe for selective detection of cyanide (CN(-)). Lys AuNCs had an average size of 4 nm and showed a red emission at 650 nm (lambdaex=370 nm). The fluorescence of Lys-AuNCs could be quenched by CN(-). An excellent sensitivity and selectivity toward the detection of CN(-) in aqueous solution was observed. The fluorescence intensity was linear with the CN(-) concentration in the range of 5.00*10(-6)M-1.20*10(-4) M with a detection limit as low as 1.9*10(-7) M. Also, the addition of CN(-) to Lys-AuNCs could induce an obvious color change from light yellow to colorless. Correspondingly, a bright red fluorescence disappeared and a blue fluorescence appeared. The results indicated that Lys-AuNCs could be applied in detection of cyanide on environmental aspects. PMID- 24231740 TI - Caspase inhibition augments Dichlorvos-induced dopaminergic neuronal cell death by increasing ROS production and PARP1 activation. AB - Numerous epidemiological studies have shown an association between pesticide exposure and the increased risk of developing Parkinson's disease. Previously we have reported that Dichlorvos exposure can induce oxidative stress, resulting in over-expression of pro-apoptotic genes and finally caspase-dependent nigrostriatal dopaminergic neuronal cell death in rat brain. Here, we examined the effect of caspase inhibition on PC12 cell death induced by Dichlorvos (30 MUM). Reactive oxygen species (ROS) generation followed by protein carbonylation, lipid peroxidation, decreased antioxidant defenses (decreased Mn-superoxide dismutase (MnSOD) activity and decreased glutathione levels) and subsequent caspase activation mediated the apoptosis. Inhibition of caspase cascade with Boc aspartyl(OMe)-fluoromethylketone (BAF) enhanced the Dichlorvos-induced PC12 cell death, as assessed by the increased cellular efflux of lactate dehydrogenase (LDH). This increase in cell death was accompanied by a marked increase in poly(ADP-ribose) polymerase-1 (PARP1) activity, increased oxidative stress, a reduction in the mitochondrial membrane potential and reduced cellular NAD and ATP levels. Pretreatment of cells with PJ34, a PARP1 inhibitor prevented the cells from undergoing cell death and preserved intracellular NAD and ATP levels. Subsequent release of the apoptosis-inducing factor (AIF) from mitochondria and its translocation into the nucleus was also prevented by PJ34 pretreatment. In conclusion, the results of the present study show that caspase inhibition without concurrent inhibition of PARP1 is unlikely to be effective in preventing cell death because in the presence of the caspase inhibitor, caspase-independent cell death predominates due to PARP activation. These results suggest that combined therapeutic strategies directed at multiple cell death pathways may provide superior neuroprotection than those directed at a single mechanism. PMID- 24231742 TI - Effect of bovine serum albumin and single walled carbon nanotube on the photophysical properties of zinc octacarboxy phthalocyanine. AB - This work reports on the photophysical parameters of the conjugate between zinc octacarboxy phthalocyanine (ZnOCPc) and bovine serum albumin (BSA) represented as ZnOCPc-BSA (1) which was further adsorbed onto single walled carbon nanotubes (SWCNT) represented as (ZnOCPc-BSA-SWCNT 2). ZnOCPc (without BSA) was also adsorbed on SWCNT represented as ZnOCPc-SWCNT (3). The presence of BSA resulted in the increase in singlet oxygen quantum yield (PhiDelta) for 1 (at PhiDelta=0.44) and 2 (at PhiDelta=0.41) compared to PhiDelta=0.21 for ZnOCPc alone. For complex 3 which did not contain BSA singlet oxygen quantum yield decreased. PMID- 24231743 TI - Synthesis, characterization and catalytic activity of silver nanoparticles using Tribulus terrestris leaf extract. AB - Biomediated silver nanoparticles were synthesized with the aid of an eco-friendly biomaterial, namely, aqueous Tribulus terrestris extract. Silver nanoparticles were synthesized using a rapid, single step, and completely green biosynthetic method employing aqueous T. terrestris leaf extracts as both the reducing and capping agent. Silver ions were rapidly reduced by aqueous T. terrestris leaf extracts, leading to the formation of highly crystalline silver nanoparticles. An attempt has been made and formation of the silver nanoparticles was verified by surface plasmon spectra using an UV-vis (Ultra violet), spectrophotometer. Morphology and crystalline structure of the prepared silver nanoparticles were characterized by TEM (Transmission Electron Microscope) and XRD (X-ray Diffraction), techniques, respectively. FT-IR (Fourier Transform Infrared), analysis suggests that the obtained silver nanoparticles might be stabilized through the interactions of carboxylic groups, carbonyl groups and the flavonoids present in the T. terrestris extract. PMID- 24231744 TI - Highly stable water dispersible calix[4]pyrrole octa-hydrazide protected gold nanoparticles as colorimetric and fluorometric chemosensors for selective signaling of Co(II) ions. AB - Water dispersible stable gold nanoparticles (AuNps) have been synthesized by using calix[4]pyrrole octa-hydrazide (CPOH) as a reducing as well as stabilizing agent. CPOH-AuNps have been characterized by surface plasmon resonance, particle size analyzer and transmission electron microscopy. CPOH-AuNps are water dispersible, highly stable for more than 150 days at neutral pH with a size of less than 10nm and zeta potential of 15+/-2 MeV. Ion sensing property of CPOH AuNps has been investigated for various metal ions Pb(II), Cd(II), Mn(II), Fe(III), Ni(II), Zn(II), Hg(II), Co(II) and Cu(II) by colorimetry and spectrofluorimetry. Among all the metal ions investigated, only Co(II) ions gives sharp colour change from ruby red to blue and is easily detectable by naked-eye. CPOH-AuNps being fluorescent in nature also shows great sensitivity and selectivity for Co(II) ions. Co(II) ions can be selectively detected at very low concentration level of 1 nM in a facile way of fluorescence quenching. PMID- 24231745 TI - Zinc (II) complex with a cationic Schiff base ligand: synthesis, characterization, and biological studies. AB - A cationic Schiff base ligand, TSB (L) and its Zn (II) complex (1) were synthesized and characterized by using CHN, (1)H-NMR, FT-IR, UV, LC-MS, and X-ray methods. Their ability to inhibit topoisomerase I, DNA cleavage activities, and cytotoxicity were studied. X-ray diffraction study shows that the mononuclear complex 1 is four coordinated with distorted tetrahedral geometry. The singly deprotonated Schiff base ligand L acts as a bidentate ON-donor ligand. Complexation of L increases the inhibitory strength on topoisomerase I activity. Complex 1 could fully inhibit topoisomerase I activity at 250 MUM, while L did not show any inhibitory effect on topoisomerase I activity. In addition, L and complex 1 could cleave pBR322 DNA in a concentration and time dependent profile. Surprisingly, L has better DNA cleavage activity than complex 1. The cleavage of DNA by complex 1 is altered in the presence of hydrogen peroxide. Furthermore, L and complex 1 are mildly cytotoxic towards human ovarian cancer A2780 and hepatocellular carcinoma HepG2. PMID- 24231746 TI - Spectroscopic studies on the interaction of Ga3+-hypocrellin A with myoglobin. AB - In this article, the interaction mechanism of Ga(3+)-hypocrellin A (Ga(3+)-HA) with myoglobin (Mb) is studied in detail through various spectroscopic technologies. UV-vis absorption and fluorescence spectra demonstrate the interaction process. The Stern-Volmer plot and the time-resolved fluorescence study suggest the fluorescence quenching mechanism of Mb by Ga(3+)-HA is a static quenching procedure, and the electronic transfer forces play a major role in binding Ga(3+)-HA to Mb. Furthermore, synchronous fluorescence studies and circular dichroism (CD) spectra reveal that the conformation of Mb is changed after its conjugation with Ga(3+)-HA. PMID- 24231747 TI - Selective recognition of dysprosium(III) ions by enhanced chemiluminescence CdSe quantum dots. AB - The intensity of emitted light from CdSe quantum dots (QDs)-H2O2 is described as a novel chemiluminescence (CL) reaction for determination of dysprosium. This reaction is based on the catalytic effect of Dy(3+) ions, causing a significant increase in the light emission, as a result of the reaction of quantum dots (QDs) with hydrogen peroxide. In the optimum conditions, this method was satisfactorily described by linear calibration curve in the range of 8.3*10(-7)-5.0*10(-6)M, the detection limit of 6.0*10(-8)M, and the relative standard deviation for five determinations of 2.5*10(-6)M Dy(3+) 3.2%. The main experimental advantage of the proposed method is its selective to Dy(3+) ions compared with common coexisting cations, therefore, it was successfully applied for the determination of dysprosium ions in water samples. PMID- 24231748 TI - Vibrational characterization and adsorption mode on SERS-active surfaces of guanidino-(bromophenyl)methylphosphonic acid. AB - This work presents adsorption geometry of [N-butyl-guanidino-(4 bromophenyl)methyl] phosphonic acid (4-BrPhG(n-But)P) on different SERS-active substrates (colloidal and specifically prepared Ag and Au roughened substrates). The adsorption mode is deduced from the SERS selection rules and several characteristic bands of the 4-BrPhG(n-But)P molecular fragments. The SERS spectra are compared to the experimental FT-Raman spectrum. In addition, the vibrational wavenumbers and PED's obtained for 4-BrPhG(n-But)P by using density functional theory methods with B3LYP/6-311++G(**) level of theory and PCM model is briefly presented. PMID- 24231749 TI - Vibrational spectra, optical properties, NBO and HOMO-LUMO analysis of L Phenylalanine L-Phenylalaninium Perchlorate: DFT calculations. AB - In this work, we report a combined experimental and theoretical study of a nonlinear optical material, L-Phenylalanine L-Phenylalaninium Perchlorate. Single crystals of the title compound have been grown by slow evaporation of an aqueous solution at room temperature. Theoretical calculations were preceded by redetermination of the crystal X-ray structure. The compound crystallizes in the non-centro symmetric space group P2(1)2(1)2(1) of the orthorhombic system. The FT IR and Raman spectra of the crystal were recorded and analyzed. The density functional theory (DFT) computations have been performed at B3LYP/6-31G(d) level to derive equilibrium geometry, vibrational wavenumbers, intensity and NLO properties. All observed vibrational bands have been discussed and assigned to normal mode or to combinations on the basis of our DFT calculations as a primary source of attribution and also by comparison with the previous results for similar compounds. Natural bond orbital analysis was carried out to demonstrate the various inter-and intramolecular interaction that are responsible of the stabilization of the compound. The lowering of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap appears to be the cause of its enhanced charge transfer interaction leading to high NLO activity. PMID- 24231750 TI - Dithizone as novel and efficient chromogenic probe for cyanide detection in aqueous media through nucleophilic addition into diazenylthione moiety. AB - A new selective chemodosimeter probe was developed by the introduction of dithizone (DTZ) as a simple and available dye for detection of cyanide in aqueous media which enables recognition of cyanide over other competing anions such as acetate, dihydrogen phosphate, fluoride and benzoate through covalent bonding. The sensing properties of DTZ were investigated in DMSO/H2O (1:9) and have demonstrated a very high selectivity toward the cyanide anions. A reasonable recognition mechanism was suggested using UV-Vis, (1)H NMR and FTIR spectroscopy techniques. Time dependent density function theory (TDDFT) computations of UV-Vis excitation for DTZ2-CN adduct agreed well with our experimental findings. The detection limit of the new chromogenic probe was measured to be 0.48 MUmol L(-1) which is much lower than most recently reported chromogenic probes for cyanide determination. The analytical utility of the method for the analysis of cyanide ions in electroplating wastewater (EPWW), human serum, tap and mineral water samples was demonstrated and the results were compared successfully with the conventional reference method. The short time response and the detection by the naked eye make the method available for the detection and quantitative determination of cyanide in a variety of real samples. PMID- 24231751 TI - Coxsackievirus A16: epidemiology, diagnosis, and vaccine. AB - Coxsackievirus 16 (CA16) is one of the major pathogens associated with hand, foot, and mouth disease (HFMD) in infants and young children. In recent years, CA16 and human enterovirus 71 (EV71) have often circulated alternatively or together in the Western Pacific region, which has become an important public health problem in this region. HFMD caused by CA16 infection is generally thought to be mild and self-limiting. However, recently several severe and fatal cases involving CA16 have been reported. Studies have shown that co-infection with CA16 and EV71 can cause serious complications in the central nervous system (CNS) and increase the chance of genetic recombination, which may be responsible for the large HFMD outbreak in Mainland China in 2008. For these reasons, recent studies have focused on the virological characteristics of CA16 and the development of CA16-related diagnostic reagents and vaccines. PMID- 24231752 TI - The effects of assisted ergometer training with a functional electrical stimulation on exercise capacity and functional ability in subacute stroke patients. AB - OBJECTIVE: To determine if assistive ergometer training can improve the functional ability and aerobic capacity of subacute stroke patients and if functional electrical stimulation (FES) of the paretic leg during ergometer cycling has additional effects. METHODS: Sixteen subacute stroke patents were randomly assigned to the FES group (n=8) or the control group (n=8). All patients underwent assistive ergometer training for 30 minutes (five times per week for 4 weeks). The electrical stimulation group received FES of the paretic lower limb muscles during assistive ergometer training. The six-minute walk test (6MWT), Berg Balance Scale (BBS), and the Korean version of Modified Barthel Index (K MBI) were evaluated at the beginning and end of treatment. Peak oxygen consumption (Vo2peak), metabolic equivalent (MET), resting and maximal heart rate, resting and maximal blood pressure, maximal rate pressure product, submaximal rate pressure product, submaximal rate of perceived exertion, exercise duration, respiratory exchange ratio, and estimated anaerobic threshold (AT) were determined with the exercise tolerance test before and after treatment. RESULTS: At 4 weeks after treatment, the FES assistive ergometer training group showed significant improvements in 6MWT (p=0.01), BBS (p=0.01), K-MBI (p=0.01), Vo2peak (p=0.02), MET (p=0.02), and estimated AT (p=0.02). The control group showed improvements in only BBS (p=0.01) and K-MBI (p=0.02). However, there was no significant difference in exercise capacity and functional ability between the two groups. CONCLUSION: This study demonstrated that ergometer training for 4 weeks improved the functional ability of subacute stroke patients. In addition, aerobic capacity was improved after assisted ergometer training with a FES only. PMID- 24231753 TI - Comparative analysis of several detectors for the measurement of radiation transmission and leakage from a multileaf collimator. AB - The multileaf collimator (MLC) is the standard device used to shape radiation beams for 3-d conformal and intensity-modulated radiation therapy (IMRT). Due to the inherent properties of MLC, there is a small amount of radiation transmitted through the leaves, called radiation transmission (RT). Accurate measurements of this radiation are required to commission and validate IMRT-capable treatment planning systems because this radiation may impact the dosimetry of IMRT calculated dose distributions. This work compares several detectors in the measurement of RT for a micro-multileaf collimation system. The results show that there are statistically significant differences in the measured RT values between detectors from 3.5 to 12.5% for the same MLC model and less than 0.2% relative to the isocentre dose for an open reference field. However, although small in magnitude, these differences may impact the dosimetry of IMRT treatment planning by up to 1.78 Gy to the healthy tissue surrounding the target for a treatment of 60 Gy in 30 fractions. By the later, these differences must be included as a source of uncertainty in IMRT dose delivery. Also, it must be established which detector offers the most reliable results in the measurement of the RT by using Monte Carlo simulation methods. PMID- 24231754 TI - Endoglin (CD105) is a more appropriate marker than CD31 for detecting microvessels in carotid artery plaques. AB - BACKGROUND: Microvascular proliferation is a major risk factor for plaque vulnerability in patients with carotid stenosis. There are several vascular endothelial markers such as CD31 and CD105, but it is unclear which marker is most sensitive for microvessels. This study sought to examine the correlations between CD31 and CD105 expression in microvessels on carotid plaques and clinical manifestations. METHODS: We studied 13 lesions in 12 patients. The patients underwent carotid endarterectomy and samples were stained for CD31 and CD105. The numbers of microvessels positive for these markers within a field of view were counted. RESULTS: The average numbers of microvessels were 5.8 +/- 5.4 for CD31 and 9.2 +/- 9.3 for CD105 (P = 0.04). More microvessels were positive for CD105 than there were for CD31 in patients with diabetes mellitus (P = 0.04). CONCLUSION: In patients with carotid artery stenosis, CD105 is more appropriate than CD31 for detecting microvessels in carotid plaques. In patients with diabetes mellitus, CD105 is significantly more highly expressed in microvessels than CD31. PMID- 24231755 TI - Hydrothermally formed functional niobium oxide doped tungsten nanorods. AB - Nanorod forms of metal oxides are recognized as one of the most remarkable morphologies. Their structure and functionality have driven important advancements in a vast range of electronic devices and applications. In this work, we postulate a novel concept to explain how numerous localized surface states can be engineered into the bandgap of niobium oxide nanorods using tungsten. We discuss their contributions as local state surface charges for the modulation of a Schottky barrier height, the relative dielectric constant and their respective conduction mechanisms. Their effects on hydrogen gas molecule interaction mechanisms are also examined herein. We synthesized niobium tungsten oxide (Nb17W2O25) nanorods via a hydrothermal growth method and evaluated the Schottky barrier height, ideality factor, dielectric constant and trap energy level from the measured I-V versus temperature characteristics in the presence of air and hydrogen to show the validity of our postulations. PMID- 24231756 TI - Quadrivalent influenza vaccine in the United States. AB - New strategies to improve influenza vaccines are ongoing. With the recent development of new vaccine formulations, such improvement are have begun to materialize in formulations available to providers and their patients. One of the newest strategies developed has been to broaden the composition of the current influenza vaccine formulations from trivalent products to quadrivalent products. To date, three manufacturers have developed and tested four vaccine formulations for safety and immunogenicity. The growing availability of quadrivalent influenza vaccines is now a well-recognized advance among the growing opportunities to improve influenza prevention. PMID- 24231757 TI - The role of leptin in the development of pulmonary neutrophilia in infection and acute lung injury. AB - OBJECTIVES: One of the hallmarks of severe pneumonia and associated acute lung injury is neutrophil recruitment to the lung. Leptin is thought to be up regulated in the lung following injury and to exert diverse effects on leukocytes, influencing both chemotaxis and survival. We hypothesized that pulmonary leptin contributes directly to the development of pulmonary neutrophilia during pneumonia and acute lung injury. DESIGN: Controlled human and murine in vivo and ex vivo experimental studies. SETTING: Research laboratory of a university hospital. SUBJECTS: Healthy human volunteers and subjects hospitalized with bacterial and H1N1 pneumonia. C57Bl/6 and db/db mice were also used. INTERVENTIONS: Lung samples from patients and mice with either bacterial or H1N1 pneumonia and associated acute lung injury were immunostained for leptin. Human bronchoalveolar lavage samples obtained after lipopolysaccharide-induced lung injury were assayed for leptin. C57Bl/6 mice were examined after oropharyngeal aspiration of recombinant leptin alone or in combination with Escherichia coli- or Klebsiella pneumoniae-induced pneumonia. Leptin-resistant (db/db) mice were also examined using the E. coli model. Bronchoalveolar lavage neutrophilia and cytokine levels were measured. Leptin-induced chemotaxis was examined in human blood- and murine marrow-derived neutrophils in vitro. MEASUREMENTS AND MAIN RESULTS: Injured human and murine lung tissue showed leptin induction compared to normal lung, as did human bronchoalveolar lavage following lipopolysaccharide instillation. Bronchoalveolar lavage neutrophilia in uninjured and infected mice was increased and lung bacterial load decreased by airway leptin administration, whereas bronchoalveolar lavage neutrophilia in infected leptin-resistant mice was decreased. In sterile lung injury by lipopolysaccharide, leptin also appeared to decrease airspace neutrophil apoptosis. Both human and murine neutrophils migrated toward leptin in vitro, and this required intact signaling through the Janus Kinase 2/phosphatidylinositol 4,5-bisphosphate 3-kinase pathway. CONCLUSIONS: We demonstrate that pulmonary leptin is induced in injured human and murine lungs and that this cytokine is effective in driving alveolar airspace neutrophilia. This action appears to be caused by direct effects of leptin on neutrophils. PMID- 24231758 TI - Timing of continuous renal replacement therapy and mortality in critically ill children*. AB - OBJECTIVES: Acute kidney injury and fluid overload frequently necessitate initiation of continuous renal replacement therapy in critically ill patients admitted to the ICU. In this study, our primary objective was to determine the effect of timing of initiation of continuous renal replacement therapy on ICU mortality in children requiring renal support for management of acute kidney injury and/or fluid overload. DESIGN: Retrospective cohort study. SETTING: Tertiary level, multidisciplinary PICU. PATIENTS: Children who received continuous renal replacement therapy for management of acute kidney injury and/or fluid overload from January 2000 through July 2009 were included in the study. Patients requiring extracorporeal life support and patients initiated on continuous renal replacement therapy for indications other than acute kidney injury and/or fluid overload were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timing of initiation was defined chronologically as time from ICU admission to continuous renal replacement therapy initiation. Three hundred eighty treatments were performed during the study period, of which 190 were eligible and included in the study. Overall ICU mortality was 47% among the study population. Median timing of initiation was higher among nonsurvivors compared with survivors (3.4 vs 2.0 d, p = 0.001). Multivariable logistic regression analysis identified timing of initiation as an independent predictor of mortality with an adjusted odds ratio of 1.05 (95% CI, 1.01, 1.11). Fluid overload, indication for continuous renal replacement therapy initiation, severity of illness at ICU admission, and active oncologic diagnosis were the other independent predictors of mortality that were identified in the final regression model. In the survival analysis, late initiators (> 5 d) had higher mortality than early initiators (<= 5 d) with a hazard ratio of 1.56 (95% CI, 1.02, 2.37). CONCLUSIONS: Earlier initiation of continuous renal replacement therapy was associated with lower mortality in this cohort of critically ill children. Future studies should focus on early identification of such children who may benefit from early continuous renal replacement therapy initiation. PMID- 24231759 TI - A randomized, controlled trial of in situ pediatric advanced life support recertification ("pediatric advanced life support reconstructed") compared with standard pediatric advanced life support recertification for ICU frontline providers*. AB - OBJECTIVE: Recent evidence shows poor retention of Pediatric Advanced Life Support provider skills. Frequent refresher training and in situ simulation are promising interventions. We developed a "Pediatric Advanced Life Support reconstructed" recertification course by deconstructing the training into six 30 minute in situ simulation scenario sessions delivered over 6 months. We hypothesized that in situ Pediatric Advanced Life Support-reconstructed implementation is feasible and as effective as standard Pediatric Advanced Life Support recertification. DESIGN: A prospective randomized, single-blinded trial. SETTING: Single-center, large, tertiary PICU in a university-affiliated children's hospital. SUBJECTS: Nurses and respiratory therapists in PICU. INTERVENTIONS: Simulation-based modular Pediatric Advanced Life Support recertification training. MEASUREMENTS AND MAIN RESULTS: Simulation-based pre- and postassessment sessions were conducted to evaluate participants' performance. Video-recorded sessions were rated by trained raters blinded to allocation. The primary outcome was skill performance measured by a validated Clinical Performance Tool, and secondary outcome was behavioral performance measured by a Behavioral Assessment Tool. A mixed-effect model was used to account for baseline differences. Forty participants were prospectively randomized to Pediatric Advanced Life Support reconstructed versus standard Pediatric Advanced Life Support with no significant difference in demographics. Clinical Performance Tool score was similar at baseline in both groups and improved after Pediatric Advanced Life Support reconstructed (pre, 16.3 +/- 4.1 vs post, 22.4 +/- 3.9; p < 0.001), but not after standard Pediatric Advanced Life Support (pre, 14.3 +/- 4.7 vs post, 14.9 +/- 4.4; p =0.59). Improvement of Clinical Performance Tool was significantly higher in Pediatric Advanced Life Support reconstructed compared with standard Pediatric Advanced Life Support (p = 0.006). Behavioral Assessment Tool improved in both groups: Pediatric Advanced Life Support reconstructed (pre, 33.3 +/- 4.5 vs post, 35.9 +/- 5.0; p = 0.008) and standard Pediatric Advanced Life Support (pre, 30.5 +/- 4.7 vs post, 33.6 +/- 4.9; p = 0.02), with no significant difference of improvement between both groups (p = 0.49). CONCLUSIONS: For PICU-based nurses and respiratory therapists, simulation-based "Pediatric Advanced Life Support-reconstructed" in situ training is feasible and more effective than standard Pediatric Advanced Life Support recertification training for skill performance. Both Pediatric Advanced Life Support recertification training courses improved behavioral performance. PMID- 24231760 TI - B-type natriuretic peptide and risk of acute kidney injury in patients hospitalized with acute coronary syndromes*. AB - OBJECTIVES: To investigate whether admission B-type natriuretic peptide levels predict the development of acute kidney injury in acute coronary syndromes. DESIGN: Prospective study. SETTING: Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. PATIENTS: Six-hundred thirty-nine acute coronary syndromes patients undergoing emergency and urgent percutaneous coronary intervention. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured B-type natriuretic peptide at hospital admission in acute coronary syndromes patients (55% ST-elevation myocardial infarction and 45% non-ST elevation myocardial infarction). Acute kidney injury was classified according to the Acute Kidney Injury Network criteria: stage 1 was defined as a serum creatinine increase greater than or equal to 0.3 mg/dL from baseline; stage 2 as a serum creatinine increase greater than two- to three-fold from baseline; stage 3 as a serum creatinine increase greater than three-fold from baseline, or greater than or equal to 4.0 mg/dL with an acute increase greater than 0.5 mg/dL, or need for renal replacement therapy. Acute kidney injury was developed in 85 patients (13%) and had a higher in-hospital mortality than patients without acute kidney injury (14% vs 1%; p < 0.001). B-type natriuretic peptide levels were higher in acute kidney injury patients than in those without acute kidney injury (264 [112-957] vs 98 [44-271] pg/mL; p < 0.001) and showed a significant gradient according to acute kidney injury severity (224 [96-660] pg/mL in stage 1 and 939 [124-1,650] pg/mL in stage 2-3 acute kidney injury; p < 0.001). The risk of developing acute kidney injury increased in parallel with B-type natriuretic peptide quartiles (5%, 9%, 15%, and 24%, respectively; p < 0.001). When B-type natriuretic peptide was evaluated, in terms of capacity to predict acute kidney injury, the area under the curve was 0.702 (95% CI, 0.642-0.762). CONCLUSIONS: In patients hospitalized with acute coronary syndromes, B-type natriuretic peptide levels measured at admission are associated with acute kidney injury as well as its severity. PMID- 24231761 TI - Do physicians have lower risk of severe sepsis and associated mortality? A matched cohort study*. AB - OBJECTIVES: Physicians generally have higher disease awareness and easier access to medical care, which may help them reduce risk of developing severe sepsis and associated mortality when they suffer from acute infection. However, the opposite situation may occur due to the presence of potential barriers to healthcare in physicians. We aim to examine the risk of severe sepsis and associated mortality in physicians. DESIGN: A matched cohort study. SETTING: Registry of medical professionals and inpatient and outpatient claims data from Taiwan's National Health Insurance Research Database. SUBJECTS: Physicians (n = 29,697) in Taiwan and a group of persons who were demographically and socioeconomically matched (1:1 ratio) and without any medical education and background. All subjects were followed from the index date (January 1, 2000) to the occurrence of endpoint, withdrawal, or December 31, 2008, whichever date came first. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was development of severe sepsis. Secondary outcome was 90-day mortality following severe sepsis. The overall incidence density of severe sepsis was lower in physicians than in controls (3.25 vs 3.90 per 1,000 person-years, p < 0.001). According to the Cox regression model, severe sepsis develops in physicians 24% less likely than controls after baseline covariates were adjusted (adjusted hazard ratio, 0.76; 95% CI, 0.68 0.85). The 90-day mortality rates were similar between physicians and controls with severe sepsis (46.5% vs 45.7%, p = 0.72). However, after controlling for the baseline and additional covariates, the risk of death was significantly lower in physicians than in controls (adjusted hazard ratio, 0.82; 95% CI, 0.71-0.95). CONCLUSIONS: These findings support the hypothesis that physicians are less likely than controls to develop or die of severe sepsis, implying that medical knowledge, higher disease awareness, and easier healthcare access in physicians may help reduce their risk of severe sepsis and associated mortality. PMID- 24231762 TI - Monitoring of spinal cord perfusion pressure in acute spinal cord injury: initial findings of the injured spinal cord pressure evaluation study*. AB - OBJECTIVES: To develop a technique for continuously monitoring intraspinal pressure at the injury site (intraspinal pressure) after traumatic spinal cord injury. DESIGN: A pressure probe was placed subdurally at the injury site in 18 patients who had isolated severe traumatic spinal cord injury (American Spinal Injuries Association grades A-C). Intraspinal pressure monitoring started within 72 hours of the injury and continued for up to a week. In four patients, additional probes were inserted to simultaneously monitor subdural pressure below the injury and extradural pressure. Blood pressure was recorded from a radial artery catheter kept at the same horizontal level as the injured segment of the spinal cord. We determined the effect of various maneuvers on spinal cord perfusion pressure and spinal cord function and assessed using a limb motor score and motor-evoked potentials. SETTING: Neurosurgery and neuro-ICU covering a 3 million population in London. SUBJECTS: Patients with severe traumatic spinal cord injury. Control subjects without spinal cord injury (to monitor spinal cerebrospinal fluid signal and motor evoked potentials). INTERVENTIONS: Insertion of subdural spinal pressure probe. MEASUREMENTS AND MAIN RESULTS: There were no procedure-related complications. Intraspinal pressure at the injury site was higher than subdural pressure below the injury or extradural pressure. Average intraspinal pressure from the 18 patients with traumatic spinal cord injury was significantly higher than average intraspinal pressure from 12 subjects without traumatic spinal cord injury. Change in arterial PCO2, change in sevoflurane dose, and mannitol administration had no significant effect on intraspinal pressure or spinal cord perfusion pressure. Increase in inotrope dose significantly increased spinal cord perfusion pressure. Bony realignment and laminectomy did not effectively lower intraspinal pressure. Laminectomy was potentially detrimental by exposing the swollen spinal cord to compression forces applied to the skin. By intervening to increase spinal cord perfusion pressure, we could increase the amplitude of motor-evoked potentials recorded from below or just above the injury level in nine of nine patients with traumatic spinal cord injury. In two of two patients with American Spinal Injuries Association grade C traumatic spinal cord injury, higher spinal cord perfusion pressure correlated with increased limb motor score. CONCLUSIONS: Our findings provide proof-of principle that subdural intraspinal pressure at the injury site can be measured safely after traumatic spinal cord injury. PMID- 24231763 TI - Inhibiting the toll-like receptor 4 Toll/interleukin-1 receptor domain protects against hepatic warm ischemia and reperfusion injury in mice. AB - OBJECTIVE: During Toll-like receptor 4 signaling, the Toll/interleukin-1 receptor domain is essential for interactions with downstream Toll/interleukin-1 receptor domain-containing adaptor proteins. The aim of this study is to investigate the role of the Toll/interleukin-1 receptor domain in the Toll-like receptor 4 signaling pathway during hepatic ischemia and reperfusion injury. DESIGN: We genetically blocked the function of Toll/interleukin-1 receptor domain in mice and examined the effect on Toll-like receptor 4 signaling and the response to hepatic ischemia and reperfusion. SETTING: University research laboratory. SUBJECTS: Male BALB/c mice. INTERVENTIONS: Male BALB/c mice were hydrodynamically administrated the target gene plasmid pTIR-IRES2-EGFP, empty vector containing enhanced green fluorescent protein, or normal saline. Animals underwent 90 minutes of partial hepatic ischemia, followed by 6 or 24 hours of reperfusion. Hepatic injury was assessed by measuring serum alanine transaminase, hepatic histology, and malondialdehyde. The expression of inflammatory cytokines and nuclear factor-kappaB phosphorylation was examined in liver tissues. Hepatic apoptosis was evaluated by caspase-3 assays, terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling staining, and the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase. MEASUREMENTS AND MAIN RESULTS: Blocking the Toll/interleukin-1 receptor domain resulted in markedly lower serum alanine transaminase levels, reduced histologic injury, and lower malondialdehyde levels following 6 or 24 hours of hepatic reperfusion than mice receiving the vector alone or normal saline. Anti Toll/interleukin-1 receptor treatment also reduced Toll-like receptor 4 expression and disrupted Toll/interleukin-1 receptor-Toll/interleukin-1 receptor interactions in Toll-like receptor 4 signaling pathways. Blocking the Toll/interleukin-1 receptor domain also prevented Toll-like receptor 4-mediated mitogen-activated protein kinase activation (via Jun N-terminal kinase and p38 mitogen-activated protein kinase), an activation that mediated liver ischemia and reperfusion injury via caspase-3 activation, resulting in increased hepatocellular apoptosis. Lastly, blocking the Toll/interleukin-1 receptor domain decreased inflammatory cytokine production by inhibiting nuclear factor-kappaB activation. CONCLUSIONS: Toll/interleukin-1 receptor domain inhibition disrupts the interaction of Toll-like receptor 4 with its adaptor proteins, which abrogates downstream signaling pathways and prevents the activation of nuclear factor-kappaB and Jun N-terminal kinase/p38. This reduction in signaling consequently reduces hepatic inflammation, cell apoptosis, and hepatic damage. Toll/interleukin-1 receptor domain-targeted therapy thus represents a new approach to inhibit the intracellular Toll-like receptor 4 signaling pathway and reveals novel therapeutic target sites, which will facilitate the development of specific therapeutic agents. PMID- 24231764 TI - Synthesis of nitrogen-doped hollow carbon nanospheres for CO2 capture. AB - Here, we report the synthesis of nitrogen-doped hollow carbon nanospheres (N HCSs) via a two-step Stober method. The resultant N-HCSs possess a uniform size of ~220 nm, a high nitrogen loading content of 14.8 wt% and a high surface area of 767 m(2) g(-1), as well as exhibit a considerable performance for CO2 capture with a capacity of 2.67 mmol g(-1) and a high selectivity in a mixture gas (N2 or O2). PMID- 24231765 TI - Microfluidic serial dilution ladder. AB - Serial dilution is a fundamental procedure that is common to a large number of laboratory protocols. Automation of serial dilution is thus a valuable component for lab-on-a-chip systems. While a handful of different microfluidic strategies for serial dilution have been reported, approaches based on continuous flow mixing inherently consume larger amounts of sample volume and chip real estate. We employ valve-driven circulatory mixing to address these issues and also introduce a novel device structure to store each stage of the dilution process. The dilution strategy is based on sequentially mixing the rungs of a ladder structure. We demonstrate a 7-stage series of 1 : 1 dilutions with R(2) equal to 0.995 in an active device area of 1 cm(2). PMID- 24231766 TI - Immunological role of C4 CC chemokine-1 from snakehead murrel Channa striatus. AB - In this study, we have reported a cDNA sequence of C4 CC chemokine identified from snakehead murrel (also known as striped murrel) Channa striatus (named as CsCC-Chem-1) normalized cDNA library constructed by Genome Sequencing FLXTM Technology (GS-FLXTM). CsCC-Chem-1 is 641 base pairs (bp) long that contain 438 bp open reading frame (ORF). The ORF encodes a polypeptide of 146 amino acids with a molecular mass of 15 kDa. The polypeptide contains a small cytokine domain at 30-88. The domain carries the CC motif at Cys(33)-Cys(34). In addition, CsCC Chem-1 consists of another two cysteine residues at C(59) and C(73), which, together with C(33) and C(34), make CsCC-Chem-1 as a C4-CC chemokine. CsCC-Chem-1 also contains a 'TCCT' motif at 32-35 as CC signature motif; this new motif may represent new characteristic features, which may lead to some unknown function that needs to be further focused on. Phylogenitically, CsCC-Chem-1 clustered together with CC-Chem-1 from rock bream Oplegnathus fasciatus and European sea bass Dicentrarchus labrax. Significantly (P<0.05) highest gene expression was noticed in spleen and is up-regulated upon fungus (Aphanomyces invadans), bacteria (Aeromonas hydrophila) and virus (poly I:C) infection at various time points. The gene expression results indicate the influence of CsCC-Chem-1 in the immune system of murrel. Overall, the gene expression study showed that the CsCC Chem-1 is a capable gene to increase the cellular response against various microbial infections. Further, we cloned the coding sequence of CsCC-Chem-1 in pMAL vector and purified the recombinant protein to study the functional properties. The cell proliferation activity of recombinant CsCC-Chem-1 protein showed a significant metabolic activity in a concentration dependent manner. Moreover, the chemotaxis assay showed the capability of recombinant CsCC-Chem-1 protein which can induce the migration of spleen leukocytes in C. striatus. However, this remains to be verified further at molecular and proteomic level. PMID- 24231767 TI - GM1 controlled lateral segregation of tyrosine kinase Lck predispose T-cells to cell-derived galectin-1-induced apoptosis. AB - One prominent immunoregulatory function of galectin-1 (Gal-1), a beta-galactoside binding mammalian lectin, is induction of apoptosis in activated T-cells by a process depending on the activity of Src family tyrosine kinase, Lck. Although the requirement for Lck in Gal-1 induced T-cell death and the ability of Gal-1 to affect the membrane localization of extracellular Gal-1-binding proteins have been well documented, the consequence of the complex and related reorganization of extra- and intracellular signaling components upon Gal-1 treatment of T-cells has not yet been revealed. Therefore, we have analyzed the plasma membrane movement of Lck upon Gal-1 triggered signaling, and the significance of this event in Gal-1 induced T-cell death. Non-receptor tyrosine kinase, Lck primarily localized in the synapse of tumor cell-T-cell during 15 min of the established direct cell contact. Later, after 30 min, a lateral segregation of Lck from the cell synapse was observed. The migration of Lck to the opposite of the cell contact apparently depended on the expression and cell surface presentation of Gal-1 on the effector (tumor) cells and was accompanied by phosphorylation on the negative regulatory tyrosine residue, Tyr505. Receptor tyrosine phosphatase, CD45 played crucial role in this event since CD45 deficiency or inhibition of its phosphatase activity resulted in the failure of Lck membrane movement. Level of the Gal-1-binding glycolipid GM1 ganglioside also essentially regulated Lck localization. Segregation of Lck and Gal-1 induced apoptosis was diminished in T cells with low GM1 expression compared to T-cells with high GM1. Our results show that spatial regulation of Lck by CD45 and GM1 ganglioside determines the outcome of apoptotic response to Gal-1 and this local regulation may occur only upon intimate effector (Gal-1 expressing) cell-T-cell attachment. PMID- 24231768 TI - miR-22 in tumorigenesis. PMID- 24231769 TI - Selecting for fitness in mammalian development. PMID- 24231770 TI - Intercellular transfer of Ras: implications for immunity. PMID- 24231771 TI - Regulation of protein trafficking: JNK3 at the Golgi complex. PMID- 24231772 TI - RNA secondary structure-dependent termination of transcription. PMID- 24231773 TI - Chromatin looping is needed for iPSC induction. PMID- 24231774 TI - Vertical distraction injury of the C4-C5 cervical spine. PMID- 24231775 TI - Facilitating surgical decisions for patients who are uncertain: a pilot surgical option process within an interdisciplinary functional restoration program. AB - BACKGROUND CONTEXT: For chronic pain patients, recovery may be slowed by indecisiveness over optional surgery. These patients may be delayed from participating in interdisciplinary functional restoration (FR), pending resolution of the surgical decision. Uncertainty about surgery or rehabilitation leads to delayed recovery. A surgical option process (SOP) was developed to permit patients with chronic disabling occupational musculoskeletal disorders to enter FR, make a final determination halfway through treatment, and return to complete rehabilitation after surgery, if surgery was elected. PURPOSE: This study assessed the frequency with which an FR program can resolve an uncertain surgical option. It also assessed program completion rate and 1-year post-program outcomes for subgroups that decline surgery, request and receive surgery, or request surgery but are denied by surgeon or insurance carrier. STUDY DESIGN: Retrospective study of a consecutive cohort. PATIENT SAMPLE: A cohort of 44 consecutively treated chronic disabling occupational musculoskeletal disorder patients were admitted to an FR program and identified as candidates for a surgical procedure but were either ambivalent about undergoing surgery, had a difference of opinion by two or more surgeons, or were denied a surgical request by an insurance carrier. Patients attended half (10 full day visits) of an FR program before making their own final determination to pursue a request or decline surgery. OUTCOME MEASURES: Patients were assessed on surgical requests and whether surgery was ultimately performed, program completion status after the surgical determination, demographic variables, and 1-year outcomes on work status, additional surgery, and other health utilization measures. METHODS: Patients became part of the SOP on program entry and were included in the study if they participated in a surgical-decision interview halfway through the program. Those who elected to decline surgery (DS) completed the program without delay, but those requesting surgery were placed on hold from the program while consultation and preauthorization steps took place. Those requesting surgery, but denied (RSD), and those undergoing surgery (US) were given the opportunity to complete FR following postoperative physical therapy or resolution of the surgical re-evaluation process. RESULTS: There were 32 DS patients (73%), indicating that a large majority of patients declined the surgery that was still being considered when offered participation in the SOP. Of the 12 patients wanting a surgery, there were four US patients who received surgery previously denied (9% of cohort), and eight RSD patients (18% of cohort). Patients from the DS group completed the FR program at an 88% rate, as did 75% of US patients. However, despite an opportunity to re-enter and complete rehab, only 50% of RSD patients completed the FR option. Overall, patients who persistently sought surgery, contrary to the recommendations of a surgeon, had poorer outcomes. These 1-year post-FR outcomes included lower return-to-work and work retention rates, with higher rates of treatment seeking from new providers (resulting in higher rates of post-discharge surgery) and higher rates of recurrent injury claims after work return. CONCLUSIONS: A SOP tied to participation in an interdisciplinary FR program resolves uncertainty regarding surgical options in a high proportion of cases, resulting in a large majority declining surgery and completing the FR program. Timely surgery is also promoted decisively when needed. Findings suggest that patients who persistently seek surgery, contrary to the recommendations of a surgeon, frequently fail to complete FR and have poorer outcomes overall. PMID- 24231776 TI - Does source of funding and conflict of interest influence the outcome and quality of spinal research? AB - BACKGROUND/CONTEXT: There has been longstanding controversy surrounding the influence of funding source on the conduct and outcome of medical research. In 2011, a systematic review of the use of recombinant bone morphogenetic protein-2 revealed underreporting of unfavorable outcomes in some industry-sponsored trials. We hypothesize that Industrial funding and the presence of potential conflict of interest will be associated with low levels of evidence (LOE) and greater proportions of favorable outcomes in spinal research. PURPOSE: The aim of this study is to investigate the association between funding source and potential conflict of interest on the LOE and study outcome in the current spinal research. STUDY DESIGN/SETTING: Systematic review of all the spinal publications in five leading spinal, orthopedics, neurosurgery, and general medical journals during 2010 (print and online). Supplements were included. OUTCOME MEASURE: Outcome and the LOE of research papers. METHODS: Two reviewers independently assessed all publications. Commentaries, editorials, letters, open operating theatres, case reports, narrative reviews, and study protocols were excluded. The self-reported potential conflict of interest and type of funding was extracted from each paper. Funding type was classified as foundation, industry, public, intramural, multiple (including industry), multiple (without industry), and unfunded. The outcome of each study was classified as favorable, unfavorable, equivocal, or not applicable. Clinical publications were ranked using the LOE guidelines produced by the Oxford Center for Evidence-Based Medicine. RESULTS: Overall, 1356 papers were analyzed, out of which 864 were suitable for LOE grading. There was good interobserver reliability for assignment of LOE grade, kappa=0.897 (p<.01) and study outcome kappa=0.804 (p<.01). A significant association was found between LOE and source of funding (p<.01). Industry-funded studies had the greatest proportion of level IV evidence (65%). There was a significant association between the funding source and study outcome (p=.01). The proportion of industry funded studies with favorable outcomes (88%) was higher than that of publicly and foundation-funded studies (73% and 74%, respectively). The associated odds ratio for reporting favorable outcomes in industry-funded studies compared with studies with public and foundation funding was 2.7 (95% confidence interval [CI], 1.4 5.3), and 2.6 (95% CI, 1.3-5.2), respectively. A significant association between LOE and study outcome (p<.01) was also identified. Level I studies had the highest proportions of unfavorable (14%) and equivocal (23%) outcomes. Level IV studies had the highest proportion of favorable outcome (85%). There was no association between self-reported conflict of interest and LOE (p=.83) or study outcome (p=.25). CONCLUSION: We demonstrated a significant association between source of funding, study outcome, and LOE in spinal research. A large proportion of industry funded research was shown to provide level IV evidence and report favorable outcome. PMID- 24231777 TI - Rapid sensitive molecular diagnosis of pyogenic spinal infections using methicillin-resistant Staphylococcus-specific polymerase chain reaction and 16S ribosomal RNA gene-based universal polymerase chain reaction. AB - BACKGROUND CONTEXT: Rapid diagnosis and accurate detection of etiological agents in pyogenic spinal infection (PSI) patients are important. PURPOSE: The purpose of this study was to evaluate the clinical usefulness of methicillin-resistant Staphylococcus-specific polymerase chain reaction (MRS-PCR) and broad-range universal PCR (U-PCR) for diagnosing PSI. STUDY DESIGN: A prospective diagnostic study. PATIENTS: Thirty-two clinically suspect PSI patients and six control patients who underwent computerized tomography-guided biopsy and/or surgical treatment were enrolled. METHODS: Tissue samples were examined by microbiological culture, histopathology, and real-time PCR (MRS-PCR and U-PCR). The diagnostic accuracy of real-time PCR was analyzed based on the definitive diagnosis of infection, defined as a positive result from microbiological culture or histopathology. RESULTS: All six control subjects were negative for PSI for all analyses. Twelve clinically suspect PSI subjects received definitive diagnoses (PSI group). The non-PSI group consisted of six control subjects plus the remaining 20 patients from the PSI clinically suspect group. MRS-PCR results were positive for all MRS-cultured PSI subjects. U-PCR was positive for all subjects in the PSI group with one discrepancy between real-time PCR and microbiological culture results in differentiation between gram-positive and gram-negative bacteria. In the non-PSI group, MRS-PCR and U-PCR were positive in three and seven cases, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MRS-PCR for diagnosing MRS infection were 1.00, 0.91, 0.57, and 1.00, respectively; those for the diagnosis of bacterial infection with U-PCR were 1.00, 0.73, 0.63, and 1.00, respectively. CONCLUSION: Identification of MRS infection and ability to differentiate between gram positive and gram-negative bacteria is rapidly achieved using MRS-PCR and U-PCR. Real-time PCR provides a sensitive molecular diagnosis of PSI and may contribute to antibiotic selection. PMID- 24231778 TI - Spinal epidural abscesses: risk factors, medical versus surgical management, a retrospective review of 128 cases. AB - BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is a rare, serious and increasingly frequent diagnosis. Ideal management (medical vs. surgical) remains controversial. PURPOSE: The purpose of this study is to assess the impact of risk factors, organisms, location and extent of SEA on neurologic outcome after medical management or surgery in combination with medical management. STUDY DESIGN: Retrospective electronic medical record (EMR) review. PATIENT SAMPLE: We included 128 consecutive, spontaneous SEA from a single tertiary medical center, from January 2005 to September 11. There were 79 male and 49 female with a mean age of 52.9 years (range, 22-83). OUTCOME MEASURES: Patient demographics, presenting complaints, radiographic features, pre/post-treatment neurologic status (ASIA motor score [MS] 0-100), treatment (medical vs. surgical) and clinical follow-up were recorded. Neurologic status was determined before treatment and at last available clinical encounter. Imaging studies reviewed location/extent of pathology. METHODS: Inclusion criteria were a diagnosis of a bacterial SEA based on radiographs and/or intraoperative findings, age greater than 18 years, and adequate EMR. Exclusion criteria were postinterventional infections, Pott's disease, isolated discitis/osteomyelitis, treatment initiated at an outside facility, and imaging suggestive of a SEA but negative intraoperative findings/cultures. RESULTS: The mean follow-up was 241 days. The presenting chief complaint was site-specific pain (100%), subjective fevers (50%), and weakness (47%). In this cohort, 54.7% had lumbar, 39.1% thoracic, 35.9% cervical, and 23.4% sacral involvement spanning an average of 3.85 disc levels. There were 36% ventral, 41% dorsal, and 23% circumferential infections. Risk factors included a history of IV drug abuse (39.1%), diabetes mellitus (21.9%), and no risk factors (22.7%). Pathogens were methicillin-sensitive Staphylococcus aureus (40%) and methicillin-resistance S aureus (30%). Location, SEA extent, and pathogen did not impact MS recovery. Fifty-one patients were treated with antibiotics alone (group 1), 77 with surgery and antibiotics (group 2). Within group 1, 21 patients (41%) failed medical management (progressive MS loss or worsening pain) requiring delayed surgery (group 3). Irrespective of treatment, MS improved by 3.37 points. Thirty patients had successful medical management (MS: pretreatment, 96.5; post-treatment, 96.8). Twenty-one patients failed medical therapy (41%; MS: pretreatment, 99.86, decreasing to 76.2 [mean change, -23.67 points], postoperative improvement to 85.0; net deterioration, 14.86 points). This is significantly worse than the mean improvement of immediate surgery (group 2; MS: pretreatment, 80.32; post-treatment, 89.84; recovery, 9.52 points). Diabetes mellitus, C-reactive protein greater than 115, white blood count greater than 12.5, and positive blood cultures predict medical failure: None of four parameters, 8.3% failure; one parameter, 35.4% failure; two parameters, 40.2% failure; and three or more parameters, 76.9% failure. CONCLUSION: Early surgery improves neurologic outcomes compared with surgical treatment delayed by a trial of medical management. More than 41% of patients treated medically failed management and required surgical decompression. Diabetes, C-reactive protein greater than 115, white blood count greater than 12.5, and bacteremia predict failure of medical management. If a SEA is to be treated medically, great caution and vigilance must be maintained. Otherwise, early surgical decompression, irrigation, and debridement should be the mainstay of treatment. PMID- 24231779 TI - Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients. AB - BACKGROUND CONTEXT: Existing research on lumbar disc degeneration has remained inconclusive regarding its etiology, pathogenesis, symptomatology, prevention, and management. Degenerative disc disease (DDD) and disc prolapse (DP) are common diseases affecting the lumbar discs. Although they manifest clinically differently, existing studies on disc degeneration have included patients with both these features, leading to wide variations in observations. The possible relationship or disaffect between DDD and DP is not fully evaluated. PURPOSE: To analyze the patterns of lumbar disc degeneration in patients with chronic back pain and DDD and those with acute DP. STUDY DESIGN: Prospective, magnetic resonance imaging-based radiological study. METHODS: Two groups of patients (aged 20-50 years) were prospectively studied. Group 1 included patients requiring a single level microdiscectomy for acute DP. Group 2 included patients with chronic low back pain and DDD. Discs were assessed by magnetic resonance imaging through Pfirmann grading, Schmorl nodes, Modic changes, and the total end-plate damage score for all the five lumbar discs. RESULTS: Group 1 (DP) had 91 patients and group 2 (DDD) had 133 patients. DP and DDD patients differed significantly in the number, extent, and severity of degeneration. DDD patients had a significantly higher number of degenerated discs than DP patients (p<.000). The incidence of multilevel and pan-lumbar degeneration was also significantly higher in DDD group. The pattern of degeneration also differed in both the groups. DDD patients had predominant upper lumbar involvement, whereas DP patients had mainly lower lumbar degeneration. Modic changes were more common in DP patients, especially at the prolapsed level. Modic changes were present in 37% of prolapsed levels compared with 9.9% of normal discs (p<.00). The total end-plate damage score had a positive correlation with disc degeneration in both the groups. Further the mean total end-plate damage score at prolapsed level was also significantly higher. CONCLUSION: The results suggest that patients with disc prolapse, and those with back pain with DDD are clinically and radiologically different groups of patients with varying patterns, severity, and extent of disc degeneration. This is the first study in literature to compare and identify significant differences in these two commonly encountered patient groups. In patients with single-level DP, the majority of the other discs are nondegenerate, the lower lumbar spine is predominantly involved and the end-plate damage is higher. Patients with back pain and DDD have larger number of degenerate discs, early multilevel degeneration, and predominant upper lumbar degeneration. The knowledge that these two groups of patients are different clinically and radiologically is critical for our improved understanding of the disease and for future studies on disc degeneration and disc prolapse. PMID- 24231780 TI - Positional change of hyoid bone after anesthesia in anterior surgery of upper cervical spine. AB - BACKGROUND CONTEXT: The hyoid bone is used as a landmark in anterior upper cervical spine operations and is supposed to represent the level of C3 body. However, this correspondence between hyoid bone position and cervical level is not static and changes during surgery (extension after anesthesia). PURPOSE: To find the cervical level corresponding to the position of hyoid bone before and after anesthesia and to evaluate the adequacy of its usage as a surgical landmark. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: One hundred twenty eight patients with degenerative cervical diseases who had undergone anterior cervical discectomy and fusion. OUTCOME MEASURE: Radiologic measure. METHODS: For each patient, preanesthesia neutral, preanesthesia extension, and postanesthesia induction extension C-spine lateral image were obtained. The level of cervical vertebra that midline of hyoid bone indicated was measured by radiological method. A cervical vertebra was divided into three segments, consisting of upper half, lower half, and disc space, and each of these segments was considered as one level. The differences between pre- and postanesthesia induction hyoid positions were classified as minimal change (one level or less) and significant change (two levels or greater). Relationship between positional change of hyoid bone to gender, obesity, and age were respectively investigated. RESULTS: There were 20 cases of one-level distal displacement of the hyoid bone, 40 cases of two level distal displacement, 34 cases of three-level distal displacement, 16 cases of 4-level distal displacement, and two cases of five-level distal displacement. In eight cases, there was no level change, and in the remaining 8 cases, the hyoid bone had been displaced proximally. There were 34 cases of minimal change. The remaining 94 cases (73.4%) had significant changes. No respective relationship was found between sex, obesity, age and pre-and postanesthesia induction positional change of hyoid bone. CONCLUSIONS: Among the 128 cases studied, 73.4% hyoid bone positions had changed by more than one cervical vertebra body between the pre- to postanesthesia induction X-ray images. Sex, age, and body mass index were not associated with statistically significant differences in these positions. The hyoid bone should not be trusted as a landmark for upper cervical operations, and the cervical level to be operated should be confirmed by a radiological method before a skin incision is made. PMID- 24231781 TI - Differences in early sagittal plane alignment between thoracic and lumbar adolescent idiopathic scoliosis. AB - BACKGROUND CONTEXT: It has previously been shown that rotational stability of spinal segments is reduced by posteriorly directed shear loads that are the result of gravity and muscle tone. Posterior shear loads act on those segments of the spine that are posteriorly inclined, as determined by each individual's inherited sagittal spinal profile. Accordingly, it can be inferred that certain sagittal spinal profiles are more prone to develop a rotational deformity that may lead to idiopathic scoliosis; and lumbar scoliosis, on one end of the spectrum, develops from a different sagittal spinal profile than thoracic scoliosis on the other end. PURPOSE: To examine the role of sagittal spinopelvic alignment in the etiopathogenesis of different types of idiopathic scoliosis. STUDY DESIGN/SETTING: Multicenter retrospective analysis of lateral radiographs of patients with small thoracic and lumbar adolescent idiopathic scoliotic curves. PATIENTS SAMPLE: We included 192 adolescent idiopathic scoliosis patients with either a thoracic (n=128) or lumbar (n=64) structural curve with a Cobb angle of less than 20 degrees were studied. Children with other spinal pathology or with more severe idiopathic scoliosis were excluded, because this disturbs their original sagittal profile. Subjects who underwent scoliosis screening and had a normal spine were included in the control cohort (n=95). OUTCOME MEASURES: Thoracic kyphosis, lumbar lordosis, T9 sagittal offset, C7 and T4 sagittal plumb lines, pelvic incidence, pelvic tilt, and sacral slope, as well as parameters describing orientation in space of each individual vertebra between C7 and L5 and length of the posteriorly inclined segment. METHODS: On standardized lateral radiographs of the spine, a systematic, semi-automatic measurement of the different sagittal spinopelvic parameters was performed for each subject using in house developed computer software. RESULTS: Early thoracic scoliosis showed a significantly different sagittal plane from lumbar scoliosis. Furthermore, both scoliotic curve patterns were different from controls, but in a different sense. Thoracic kyphosis was significantly decreased in thoracic scoliosis compared with both lumbar scoliosis patients and controls. For thoracic scoliosis, a significantly longer posteriorly inclined segment, and steeper posterior inclination of C7-T8 was observed compared with both lumbar scoliosis and controls. In lumbar scoliosis, the posteriorly inclined segment was shorter and located lower in the spine, and T12-L4 was more posteriorly inclined than in the thoracic group. The lumbar scoliosis cohort had a posteriorly inclined segment of the same length as controls, but T12-L2 showed steeper posterior inclination. Lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope, however, were similar for the two scoliotic subgroups as well as the controls. CONCLUSIONS: This study demonstrates that even at an early stage in the condition, the sagittal profile of thoracic adolescent idiopathic scoliosis differs significantly from lumbar scoliosis, and both types of scoliosis differ from controls, but in different aspects. This supports the theory that differences in underlying sagittal profile play a role in the development of different types of idiopathic scoliosis. PMID- 24231782 TI - Lumbar surgery in work-related chronic low back pain: can a continuum of care enhance outcomes? AB - BACKGROUND CONTEXT: Systematic reviews of lumbar fusion outcomes in purely workers' compensation (WC) patient populations have indicated mixed results for efficacy. Recent studies on lumbar fusions in the WC setting have reported return to-work rates of 26% to 36%, reoperation rates of 22% to 27%, and high rates of persistent opioid use 2 years after surgery. Other types of lumbar surgery in WC populations are also acknowledged to have poorer outcomes than in non-WC. The possibility of improving outcomes by employing a biopsychosocial model with a continuum of care, including postoperative functional restoration in this "at risk" population, has been suggested as a possible solution. PURPOSE: To compare objective socioeconomic and patient-reported outcomes for WC patients with different lumbar surgeries followed by functional restoration, relative to matched comparison patients without surgery. STUDY DESIGN/SETTING: A prospective cohort study of chronic disabling occupational lumbar disorder (CDOLD) patients with WC claims treated in an interdisciplinary functional restoration program. PATIENT SAMPLE: A consecutive cohort of 564 patients with prerehabilitation surgery completed a functional restoration and was divided into groups based on surgery type: lumbar fusion (F group, N=331) and nonfusion lumbar spine surgery (NF group, N=233). An unoperated comparison group was matched for length of disability (U group, N=349). OUTCOME MEASURES: Validated patient-reported measures of pain, disability, and depression were administered pre- and postrehabilitation. Socioeconomic outcomes were collected via a structured 1-year "after" interview. METHODS: All patients completed an intensive, medically supervised functional restoration program combining quantitatively directed exercise progression with a multimodal disability management approach. The writing of this article was supported in part by National Institutes of Health Grant 1K05-MH-71892; no conflicts of interest are noted among the authors. RESULTS: The F group had a longer length of disability compared with the NF and U groups (M=31.6, 21.7, and 25.9 months, respectively, p<.001). There were relatively few statistically significant differences for any socioeconomically relevant outcome among groups, with virtually identical postrehabilitation return to-work (F=81%, NF=84%, U=85%, p=.409). The groups differed significantly after surgery on diagnosis of major depressive disorder and opioid dependence disorder as well as patient-reported depressive symptoms and pain intensity prerehabilitation. However, no significant differences in patient-reported outcomes were found postrehabilitation. Prerehabilitation opioid dependence disorder significantly predicted lower rates of work return and work retention as well as higher rates of treatment-seeking behavior. Higher levels of prerehabilitation perceived disability and depressive symptoms were significant risk factors for poorer work return and retention outcomes. CONCLUSIONS: Lumbar surgery in the WC system (particularly lumbar fusion) have the potential achieve positive outcomes that are comparable to CDOLD patients treated nonoperatively. This study suggests that surgeons have the opportunity to improve lumbar surgery outcomes in the WC system, even for complex fusion CDOLD patients with multiple prior operations, if they control postoperative opioid dependence and prevent an excessive length of disability. Through early referral of patients (who fail to respond to usual postoperative care) to interdisciplinary rehabilitation, the surgeon determining this continuum of care may accelerate recovery and achieve socioeconomic outcomes of relevance to the patient and WC jurisdiction through the combination of surgery and postoperative rehabilitation. PMID- 24231783 TI - Characteristics of the pelvic axial rotation in adolescent idiopathic scoliosis: a comparison between major thoracic curve and major thoracolumbar/lumbar curve. AB - BACKGROUND CONTEXT: As the biomechanical foundation of the spine, the pelvis was found to display rotation in the transverse plane in adolescent idiopathic scoliosis (AIS). However, the possible factors influencing the pelvic axial rotation (PAR) and its mechanism in patients with AIS remain unclear. PURPOSE: To characterize the PAR in AIS patients with right major thoracic (MT) or major left thoracolumbar/lumbar (TL/L) curve and to explore the associated influencing factors and probable mechanism of compensation by analyzing the association between PAR and other spinal radiographic parameters. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: All patients with the primary diagnosis of AIS from January 2008 to November 2009 were retrieved from our scoliosis database. OUTCOME MEASURES: Age, Cobb angle, and apex rotation of the main curve and the compensatory curve, curve flexibility, and PAR. METHODS: One-hundred thirty-two patients with right MT (14.7+/-1.8 years, 48+/-6.9 degrees ) and 83 patients with left major TL/L (14.7+/-1.5 years, 46+/-6.6 degrees ) were retrospectively reviewed. On standing full-spine posteroanterior radiographs, the PAR was quantified by the left/right hemi-pelvis width ratio (L/R ratio); then the subjects in both MT and major TL/L groups were divided into two subgroups: L/R ratio <=1 (pelvis rotated to the right, R-PAR group); and L/R ratio >1 (pelvis rotated to the left, L-PAR group). Comparisons of all variables were performed between the L- and R-PAR subgroups; correlation and regression analysis were carried out to identify the influencing factors of PAR. RESULTS: The majority of the MT and major TL/L patients (75.8% vs. 60.2%) displayed right pelvic rotation, which was in the same direction as the thoracic curve. The incidence of R-PAR was greater in the MT patients than the major TL/L ones (p=.016). Lumbar flexibility in MT patients with R-PAR was greater than in MT patients with L-PAR (0.96+/-0.27 vs. 0.81+/-0.33, p=.038), which was contrary to the findings in the major TL/L patients (L-PAR>R-PAR, 0.79+/-0.15 vs. 0.70+/-0.22, p=.024). In the MT patients with R-PAR, the L/R ratio showed significant positive correlations with the lumbar Cobb angle (r=0.424) as well as with the apex rotation (r=0.488), which was further identified as an influencing factor (R=0.418) of the PAR. Significant positive correlations between L/R ratio and thoracic apex rotation (r=0.361) also were detected. CONCLUSION: The majority of AIS patients with right MT or left major TL/L curves were found to have PAR to the right, in the same direction as the thoracic curve. The lumbar flexibility and apex rotation significantly influenced the PAR direction and magnitude. Moreover, the pelvis might be involved in compensation for the MT deformity through its connection with the lumbar spine. PMID- 24231784 TI - Temporal variation in surgical mortality within French hospitals. AB - BACKGROUND: Surgical mortality varies widely across hospitals, but the degree of temporal variation within individual hospitals remains unexplored and may reflect unsafe care. OBJECTIVES: To add a longitudinal dimension to large-scale profiling efforts for interpreting surgical mortality variations over time within individual hospitals. DESIGN: Longitudinal analysis of the French nationwide hospital database using statistical process control methodology. SUBJECTS: A total of 9,474,879 inpatient stays linked with open surgery from 2006 through 2010 in 699 hospitals. MEASURES: For each hospital, a control chart was designed to monitor inpatient mortality within 30 days of admission and mortality trend was determined. Aggregated funnel plots were also used for comparisons across hospitals. RESULTS: Over 20 successive quarters, 52 hospitals (7.4%) experienced the detection of at least 1 potential safety issue reflected by a substantial increase in mortality momentarily. Mortality variation was higher among these institutions compared with other hospitals (7.4 vs. 5.0 small variation signals, P<0.001). Also, over the 5-year period, 119 (17.0%) hospitals reduced and 36 (5.2%) increased their mortality rate. Hospitals with improved outcomes had better control of mortality variation over time than those with deteriorating trends (5.2 vs. 6.3 signals, P=0.04). Funnel plots did not match with hospitals experiencing mortality variations over time. CONCLUSIONS: Dynamic monitoring of outcomes within every hospital may detect safety issues earlier than traditional benchmarking and guide efforts to improve the value of surgical care nationwide. PMID- 24231785 TI - Baseline clinical HIV genotypes are a valid measure of transmitted drug resistance within the treatment-naive population. AB - OBJECTIVE: To examine whether baseline clinical genotypes are equivalent to diagnostic serum genotypes for surveillance of HIV transmitted drug resistance (TDR). DESIGN: Current HIV TDR surveillance in Canada is conducted through genotyping remnant diagnostic sera from new HIV diagnoses. As part of routine care, baseline genotyping is now conducted on all newly diagnosed HIV infections, with TDR data being generated a second time on the same patients. METHODS: Surveillance genotyping, on HIV diagnostic serum, was performed on newly diagnosed HIV cases from 2007 to 2010 in Alberta, Canada. All subjects with a baseline clinical genotype result on file, and no evidence of antiretroviral therapy, were studied further. The HIV sequences from diagnosis and from the first clinical genotype were compared according to elapsed time between testing and by evaluating timing of infection based on BED capture enzyme immunoassay (BED-CEIA, abbreviated as BED in this article). RESULTS: Eighty-seven genotype pairs were available for analysis, most of which were subtype B. The time between genotypes ranged from 0 to 755 days, with a median of 36 days and an interquartile range of 155.25 days. Genetic distance between genotypes varied between 0 and 0.03389 substitutions per site and did not correlate with sampling times. There was a tendency for the genotypes of infections classified as recent by BED to be more similar to their clinical genotypes but this effect was lost when adjusted for elapsed time between tests. There was no difference in the identified drug resistance. CONCLUSIONS: Baseline clinical genotypes from treatment-naive patients may be used for HIV TDR surveillance. PMID- 24231786 TI - Prevalence and risk factors for neutralizing antibodies to human papillomavirus types 16 and 18 in HIV-positive men who have sex with men. AB - OBJECTIVE: Human papillomavirus (HPV) vaccination is routinely recommended in HIV positive men who have sex with men (MSM) aged <= 26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types. METHODS: Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies. RESULTS: One hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend < 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012). CONCLUSIONS: A high proportion of HIV-positive MSM aged >26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged >26 years. PMID- 24231787 TI - Neuroprotective effect of ebselen against intracerebroventricular streptozotocin induced neuronal apoptosis and oxidative stress in rats. AB - The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer's disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD. PMID- 24231788 TI - Scutellaria Barbata D Don Inhibits Colorectal Cancer Growth via Suppression of Multiple Signaling Pathways. AB - The pathogenic mechanisms underlying cancer development are complex and heterogeneous, involving multiple cellular signaling transduction pathways that usually function redundantly. In addition, crosstalk between these pathways generates a complicated and robust signaling network that is regulated by compensatory mechanisms. Given the complexity of cancer pathogenesis and progression, many of the currently used antitumor agents, which typically target a single intracellular pathway, might not always be effective on complex tumor systems. Moreover, long-term use of these agents often generates drug resistance and toxicity against normal cells. Therefore, the development of novel anticancer chemotherapies is urgently needed.Scutellaria barbataD Don (SB) is a medicinal herb that has long been used in China to treat various types of cancer. We previously reported that the ethanol extract of SB (EESB) is able to induce colon cancer cell apoptosis, inhibit cell proliferation and tumor angiogenesis via modulation of several pathways, including Hedgehog, Akt, and p53. To further elucidate the precise mechanisms of SB's antitumor activity, using a colorectal cancer (CRC) mouse xenograft model in the present study, we evaluated the therapeutic efficacy and molecular mechanisms of EESB against tumor growth. We found that EESB reduced tumor volume and tumor weight but had no effect on body weight gain in CRC mice, demonstrating that EESB could inhibit colon cancer growth in vivo without apparent adverse effect. In addition, EESB treatment could significantly suppress the activation of several CRC-related pathways, including STAT3, Erk, and p38 signalings in tumor tissues, and alter the expression of multiple critical target genes such as Bcl-2, Bax, Cyclin D1, CDK4, and p21. These molecular effects lead to the induction of cancer cell apoptosis and inhibition of cell proliferation. Our findings demonstrate that SB possesses a broad range of antitumor activities because of its ability to affect multiple intracellular targets. PMID- 24231789 TI - Four new sesquiterpene lactones from the stem bark of Illicium burmanicum. AB - Four new sesquiterpene lactones (1), (2), (3), and (4), along with three known sesquiterene, namely, 6,7,10-trihydoxyisodaucane (5), 4beta,10beta dihydroxyaromadendrane (6), and sescrassidiol (7) were isolated from the stem bark of Illicium burmanicum. The structures of the new compounds were determined using 1D and 2D NMR, and HRESIMS. The anti-inflammatory activities of these compounds were evaluated by measuring the enzymatic activity of luciferase in NF kappaB reporters in a (Luc)-HEK 293 cell line treated with lipopolysaccharide (LPS). PMID- 24231790 TI - Anatomical configuration of the Sylvian fissure and its influence on outcome after pterional approach for microsurgical aneurysm clipping. AB - BACKGROUND: The sylvian fissure (SF) is the anatomical pathway used in a pterional approach, which leads to most aneurysms. There are four different anatomical variants of the SF described. In the present retrospective study the four different categories of the SF were studied in order to evaluate any correlation of these variants to surgical outcome. METHODS: Patients treated for intracranial aneurysms by a pterional transsylvian approach during 2003-2012 (N = 237) were included in the study. The SF category was determined by analysis of preoperative computed tomography (CT) scanning. Patients were grouped into unruptured intracranial aneurysms (UIA) and ruptured intracranial aneurysms with subarachnoid hemorrhage (SAH) according to the Hunt and Hess grades. Brain edema, vasospasms, ischemic lesion rate, and outcome were evaluated for possible correlation with SF anatomical variants. RESULTS: Postsurgically brain edema formation correlated significantly with more complex anatomical variants of the SF in patients with UIAs and in patients with Hunt and Hess 1 and 2. Ischemia rate, vasospasms, or clinical outcome was not negatively affected though. CONCLUSION: The classification of the SF as proposed by Yasargil is more than a pure anatomical observation. In this retrospective study, we show that the anatomical variants of the SF can be associated to postoperative complications like formation of brain edema or ischemic lesions Preoperative knowledge of the SF anatomy and possibly consecutive adapted extend of the surgical approach can decrease procedure-related morbidity. PMID- 24231791 TI - Chronic posttraumatic cartilage lesion of the knee treated with an acellular osteochondral-regenerating implant: case history with rehabilitation guidelines. AB - Osteochondral defects are often symptomatic and lead to deranged joint function. The spontaneous healing capacity of osteochondral defects is limited. In this case study, use of an acellular scaffold capable of induction of mesenchymal stem cell migration is described. This scaffold was used on an Outerbridge grade IV medical condylar defect measuring ~2 cm2. At 24 mo follow-up, the articular surface appeared restored by MRI, and the patient returned to sports. PMID- 24231792 TI - Traumatization and chronic pain: a further model of interaction. AB - Up to 80% of patients with severe posttraumatic stress disorder are suffering from "unexplained" chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes. PMID- 24231793 TI - Multi-matrix assay of cortisol, cortisone and corticosterone using a combined MEPS-HPLC procedure. AB - The development and validation of a bioanalytical assay for the simultaneous determination of cortisol, cortisone and corticosterone levels in several matrices, such as saliva, plasma, blood and urine samples have been described. The method is based on a rapid test which combines a microextraction by packed sorbent procedure and liquid chromatography-diode array technique. Chromatographic separation of the analytes (cortisol, cortisone and corticosterone) and the internal standard (methylprednisolone) was achieved in less than 10min on a reversed-phase pentafluorophenyl column using a mobile phase composed of phosphate buffer and acetonitrile. The assay was performed after an innovative microextraction procedure by means of C8 sorbent which guaranteed good clean-up of the matrices and satisfactory extraction yield of the analytes. Moreover, the method gave linear results over a range of 5-100ngmL(-1) and showed good selectivity and precision. This method was successfully applied for quantifying corticosteroids in specific matrices derived from some healthy volunteers in comparison to two socially diversified groups, namely former heroin addicts undergoing opioid replacement therapy and poly-drug abusers. PMID- 24231794 TI - N-aromatic heterocycle adducts of bulky [1,2,4-(Me3C)3C5H2]2Sm: synthesis, structure and solution analysis. AB - The reactions of the bulky samarocene [1,2,4-(Me3C)3C5H2]2Sm (1) with several N aromatic heterocycles, namely, pyridine (3), picoline (4), 4-tert-butyl-pyridine (5), isoquinoline (6) and quinoline (7), are reported. All reactions proceed smoothly in pentane in good yield and crystals of all adducts have been obtained in moderate to good yield and analyzed by X-ray crystallography. The X-ray crystal structures are in agreement with Sm(II) coordination adducts in which no electrons are transferred to the N-aromatic heterocycle. Magnetic data were recorded for 1 and for all adducts, 3-7, and reinforce the electronic structure of Sm(II), f(6) simple coordination adducts. (1)H NMR at different temperatures and visible spectroscopy in toluene show that fast exchange of the N-aromatic heterocyclic ligand (L) occurs in solution according to a ML = M + L equilibrium in which the equilibrium constant is dependent on the bulkiness of L. This fast exchange is stopped below a coalescence temperature T(c), at which the three tert butyl groups of the cyclopentadienyl are differentiated. The associated rotational barriers have been calculated. Cyclic voltammetry of 1 in THF showed a quasi-reversible wave at a reducing potential of -2.10 V versus the ferricinium/ferrocene couple for the Sm(III)-Sm(II) couple and leads to the conclusion that the non-reduction of L lies in the sterics of 1. PMID- 24231795 TI - Common diagnostic flowcharts in infective endocarditis. AB - The presentation of infective endocarditis (IE) has changed over time and its diagnosis remains difficult since it relies on the conjunction of a number of criteria which have their own limitations. The Duke classification allows for a standardized approach and is now recognized as the reference method for the diagnosis of IE. The diagnostic value of the different criteria of the Duke classification can be improved by the use of transoesophageal echocardiography for the detection of endocardial involvement and the use of non-cardiac imaging for the detection of embolic events. The number of cases of IE without identified causative microorganism can be reduced due to serological analyses and broad range polymerase chain reaction on explanted valves. Radionuclide imaging techniques are useful when the diagnosis of IE remains uncertain. [18F]FDG PET/CT can be used for the diagnosis of cardiac infection and for the detection of embolic events or metastatic infection, keeping in mind the possibility of false positive diagnosis due to its high sensitivity. Radiolabelled-leukocytes scintigraphy is more specific than [18F]FDG PET/CT and can differentiate between septic and sterile vegetations. Diagnostic flowcharts are proposed to combine the Duke classification and recent imaging techniques for the diagnostic workup of IE. PMID- 24231796 TI - Common diagnostic flowcharts in vascular and endovascular surgery. AB - Vascular and endovascular procedures are typically very "clean" procedures, with a very low infection rate. However, these complications, although rare, are unfortunately associated with a high rate of morbidity and mortality. The first rule to effectively treat the infection is always prevention, but when the infection has been established the only solution is given by an early diagnosis and proper medical care and often surgical treatment. The hardest thing is to obtain is an early and correct diagnosis, especially for low-grade infections. The purpose of our work was to strengthen the conviction that only an integrated work as a team will enable effective and quick management of this serious complication. PMID- 24231797 TI - Diagnosing diabetic foot infection: the role of imaging and a proposed flow chart for assessment. AB - Diabetes mellitus, a major current epidemic, is frequently complicated by foot infections that are associated with high morbidity. Diagnosing these infections, especially whether or not underlying bone is involved, poses clinical challenges, but is crucial to making proper decisions regarding therapeutic strategies. The most effective means of managing patients with a diabetic foot infection is within the framework of a multidisciplinary team. Present diagnostic efforts are aimed at developing better methods to differentiate uninfected from infected soft tissue wounds, to determine when bone infection is present, and to more clearly define when infection has resolved with treatment. Imaging studies play a major role in diagnosis. This usually begins with plain radiographs, but when advanced imaging is needed, magnetic resonance imaging (MRI) is considered the modality of choice. Newer techniques, such as molecular hybrid imaging, positron emission tomography (PET)/computed tomography (CT) and single photon emission (SPECT)/CT using various radiotracers, play an increasing role. These tests may redefine the non-invasive diagnostic work-up of diabetic foot wounds, potentially leading to substantial improvements in patient management. As experts in infectious diseases, radiology and nuclear medicine, we reviewed the available literature on diagnosing diabetic foot infections, especially the currently available imaging techniques, and developed a proposed diagnostic flow chart, for evaluating patients with a diabetic foot wound. PMID- 24231798 TI - Synthesis and biological evaluation of 177Lu-DOTA-porphyrin conjugate: a potential agent for targeted tumor radiotherapy detection. AB - A novel unsymmetrically substituted water soluble porphyrin derivative namely, 5 (p-amino-propylene--oxyphenyl)-10,15,20-tris-(p-carboxy-methyl-ene oxyphenyl)porphyrin was synthesized and coupled with a bifunctional chelating agent, viz. p-NCS-benzyl-DOTA (p-isothiocyanatobenzyl-1,4,7,10-tetra-aza-cyclodo decane-1,4,7,10-tetra-acetic acid) for developing a suitable conjugate for use in targeted tumor therapy. The porphyrin-p-NCS-benzyl-DOTA conjugate was radiolabeled with 177Lu in good radiolabeling yield. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumors revealed high tumor uptake (5.33+/-1.11% injected activity per gm of tumor) within 30 min post-injection. The complex exhibited favorable tumor to blood and tumor to muscle ratios at various post-administration time points. Fast clearance of the non-accumulated activity was observed mostly through the renal pathway. Scintigraphic imaging studies performed in Swiss mice bearing fibrosarcoma tumors also exhibited selective accumulation of activity in the tumor. PMID- 24231800 TI - Development of a novel water-soluble magnetic fluorescent nanoparticle for the selective detection and removal of Cu2+. AB - Recently, much attention has been paid to the selective detection and removal of Cu2+ because an excess of Cu2+ can harm the environment and living systems. Herein, we developed a novel water-soluble di-2-picolylamine/proline co-modified Fe3O4@ZnS magnetic fluorescent nanoparticle (MFNP-Cu) for the selective detection and removal of Cu2+ through a dithiocarbamate linkage strategy. The characterization of MFNP-Cu was confirmed by x-ray diffraction (XRD), transmission electron microscope (TEM), magnetization hysteresis loops, infrared (IR) and emission spectra. The results showed that MFNP-Cu could quantifiably detect Cu2+ with high sensitivity and selectivity over a broad pH range (pH 4.1 9). The maximum adsorption capacity of MFNP-Cu was calculated to be about 517.9 mg g(-1), which is higher than previously reported. This excellent property was investigated by kinetics equilibrium and thermodynamic studies. Moreover, the removal properties of MFNP-Cu toward Cu2+ from contaminated water samples was achieved by an external magnetic field. PMID- 24231801 TI - Factors associated with compliance with viscosity-modified diet among dysphagic patients. AB - OBJECTIVE: To investigate compliance with a viscosity-modified diet among Korean dysphagic patients and to determine which factors are associated with compliance. METHODS: We retrospectively reviewed medical records of patients who had been recommended to use thickeners in the previous videofluoroscopic swallowing study (VFSS). Among 68 patients, 6 were excluded because tube feeding was required due to deterioration in their medical condition. Finally, 62 patients were included in the study. Patient compliance was assessed using their medical records by checking whether he or she had maintained thickener use until the next VFSS. To determine which factors affect compliance, the relationship between thickener use and patient characteristics, such as sex, age, inpatient/outpatient status, severity of dysphagia, aspiration symptoms, follow-up interval of VFSS, and current swallowing therapy status were assessed. For noncompliers, reasons for not using thickeners were investigated by telephone interview. RESULTS: Among 62 patients, 35 (56.5%) were compliers, and 27 (43.5%) were noncompliers. Eighteen (90%) of 20 inpatients had followed previous recommendations; however, only 17 (40.5%) of 42 outpatients had been using thickeners. Of patient characteristics, only admission status was significantly correlated with compliance. When asked about the reason why they had not used thickeners, noncompliers complained about dissatisfaction with texture and taste, greater difficulty in swallowing, and inconvenience of preparing meals. CONCLUSION: Among Korean dysphagic patients, compliance with a viscosity-modified liquid diet was only about 50%. Betterments of texture and taste along with patient education might be necessary to improve compliance with thickener use. PMID- 24231799 TI - Origin, development, and differentiation of cardiac fibroblasts. AB - Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they have been historically underappreciated in terms of their functional contributions to cardiac development and physiology, they and their activated form, myofibroblasts, are now known to play key roles in both development and disease through structural, paracrine, and electrical interactions with cardiomyocytes. The lack of specific markers for fibroblasts currently convolutes the study of this dynamic cell lineage, but advances in marker analysis and lineage mapping technologies are continuously being made. Understanding how to best utilize these tools, both individually and in combination, will help to elucidate the functional significance of fibroblast-cardiomyocyte interactions in vivo. Here we review what is currently known about the diverse roles played by cardiac fibroblasts and myofibroblasts throughout development and periods of injury with the intent of emphasizing the duality of their nature. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ". PMID- 24231802 TI - Giant cell angiofibroma of the scalp: A benign rare neoplasm with bone destruction. AB - BACKGROUND: The incidence of extraorbital giant cell angiofibroma (GCA) is rare, with only one case located in the scalp reported in the literature. The morphological hallmark is histopathological examination showing richly vascularized pattern-less spindle cell proliferation containing pseudovascular spaces and floret-like multinucleate giant cells. CASE DESCRIPTION: We report a case of a 30-year-old female with a primary complaint of a painless solitary nodule arising on the left parietal region of the scalp. Complete tumor removal through surgical intervention was achieved, and the postoperative period was uneventful. CONCLUSION: Diagnosing a highly vascularized tumor in the head and neck is challenging. Our case is unique in that it is presented as a GCA of the scalp, which is an extremely rare clinical entity, and also demonstrated bone destruction. PMID- 24231803 TI - Automatic protein structure solution from weak X-ray data. AB - Determining new protein structures from X-ray diffraction data at low resolution or with a weak anomalous signal is a difficult and often an impossible task. Here we propose a multivariate algorithm that simultaneously combines the structure determination steps. In tests on over 140 real data sets from the protein data bank, we show that this combined approach can automatically build models where current algorithms fail, including an anisotropically diffracting 3.88 A RNA polymerase II data set. The method seamlessly automates the process, is ideal for non-specialists and provides a mathematical framework for successfully combining various sources of information in image processing. PMID- 24231804 TI - Crosstalk between microtubule attachment complexes ensures accurate chromosome segregation. AB - The microtubule-based mitotic spindle segregates chromosomes during cell division. During chromosome segregation, the centromeric regions of chromosomes build kinetochores that establish end-coupled attachments to spindle microtubules. Here, we used the Caenorhabditis elegans embryo as a model system to examine the crosstalk between two kinetochore protein complexes implicated in temporally distinct stages of attachment formation. The kinetochore dynein module, which mediates initial lateral microtubule capture, inhibited microtubule binding by the Ndc80 complex, which ultimately forms the end-coupled attachments that segregate chromosomes. The kinetochore dynein module directly regulated Ndc80, independently of phosphorylation by Aurora B kinase, and this regulation was required for accurate segregation. Thus, the conversion from initial dynein mediated, lateral attachments to correctly oriented, Ndc80-mediated end-coupled attachments is actively controlled. PMID- 24231805 TI - Photon-mediated interactions between distant artificial atoms. AB - Photon-mediated interactions between atoms are of fundamental importance in quantum optics, quantum simulations, and quantum information processing. The exchange of real and virtual photons between atoms gives rise to nontrivial interactions, the strength of which decreases rapidly with distance in three dimensions. Here, we use two superconducting qubits in an open one-dimensional transmission line to study much stronger photon-mediated interactions. Making use of the possibility to tune these qubits by more than a quarter of their transition frequency, we observe both coherent exchange interactions at an effective separation of 3lambda/4 and the creation of super- and subradiant states at a separation of one photon wavelength lambda. In this system, collective atom-photon interactions and applications in quantum communication may be explored. PMID- 24231806 TI - mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. AB - Mitochondrial dysfunction contributes to numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies. We found that rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases. PMID- 24231808 TI - Long-term dynamics of adaptation in asexual populations. AB - Experimental studies of evolution have increased greatly in number in recent years, stimulated by the growing power of genomic tools. However, organismal fitness remains the ultimate metric for interpreting these experiments, and the dynamics of fitness remain poorly understood over long time scales. Here, we examine fitness trajectories for 12 Escherichia coli populations during 50,000 generations. Mean fitness appears to increase without bound, consistent with a power law. We also derive this power-law relation theoretically by incorporating clonal interference and diminishing-returns epistasis into a dynamical model of changes in mean fitness over time. PMID- 24231807 TI - EMRE is an essential component of the mitochondrial calcium uniporter complex. AB - The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand containing calcium-binding proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore-forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10-kilodalton, metazoan-specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU. PMID- 24231809 TI - Nondestructive detection of an optical photon. AB - All optical detectors to date annihilate photons upon detection, thus excluding repeated measurements. Here, we demonstrate a robust photon detection scheme that does not rely on absorption. Instead, an incoming photon is reflected from an optical resonator containing a single atom prepared in a superposition of two states. The reflection toggles the superposition phase, which is then measured to trace the photon. Characterizing the device with faint laser pulses, a single photon detection efficiency of 74% and a survival probability of 66% are achieved. The efficiency can be further increased by observing the photon repeatedly. The large single-photon nonlinearity of the experiment should enable the development of photonic quantum gates and the preparation of exotic quantum states of light. PMID- 24231811 TI - Effects of examiner strength on reliability of hip-strength testing using a handheld dynamometer. AB - CONTEXT: Hip-muscle impairments are associated with a variety of lower-extremity dysfunctions. Accurate assessment in the clinical setting can be challenging due to the strength of hip muscles relative to examiner strength. OBJECTIVE: To examine the influence of examiner strength and technique on manual hip-strength testing using a handheld dynamometer. DESIGN: Repeated measures. SETTING: Research laboratory. PARTICIPANTS: 30 active adults (age 24 +/- 1.4 y). INTERVENTIONS: Three examiners of different strength performed manual muscle tests (MMT) in 2 different positions for hip extension, abduction, and external rotation using a MicroFet handheld dynamometer. Examiner strength was quantified via a 1-repetition-maximum leg press and chest press with a Keiser A420 pneumatic resistance machine. MAIN OUTCOME MEASURES: Intrarater reliability (ICC3,1), interrater reliability (ICC2,1), and measured torque values. RESULTS: Intrarater reliability for all measurements ranged from .82 to .97. Interrater reliability ranged from .81 to .98. Main effects for hip extension revealed a significant difference in torque values between examiners and between techniques. For the short-lever hipabduction and seated hip-external-rotation tests, there was a significant difference between examiners. There was no significant difference in measured torque values between examiners with the long-lever hip-abduction or the prone hip-external-rotation tests. CONCLUSIONS: MMT of the hip may be performed with high reliability by examiners of different strength. To obtain valid MMT measurements of hip muscles, examiners must consider their own strength and testing techniques employed. The authors recommend a long-lever technique for hip abduction and a prone position for testing hip external rotation to minimize the influence of examiner strength. Both positions appear to provide mechanical advantages to the examiner compared with the alternative techniques. The authors are unable to recommend a preferred hip-extension-testing technique to minimize the influence of examiner strength. PMID- 24231810 TI - Predicting pulmonary fibrosis disease course from past trends in pulmonary function. AB - BACKGROUND: The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by progressive decline in lung function and eventual mortality. We sought to determine if future declines in pulmonary function, mortality, or both can be predicted from prior trends in pulmonary function tests (PFTs). METHODS: Data from 1981 to 2008 on 4,431 PFTs and mortality were analyzed from 734 subjects with IPF. The Kaplan-Meier method was used for mortality analyses. Mixed models were used to describe longitudinal pulmonary function dynamics, since PFTs were observed at varying time points from baseline. RESULTS: During the first year of follow-up, 135 subjects (73%) had stable FVC while 50 subjects (37%) showed a decline in FVC. During months 12 to 24 (1-2 years after diagnosis), a stable FVC occurred with the same frequency among both subjects whose FVC had declined during year 1 and whose FVC had remained stable (84.0% and 80.7%, respectively; P=.59). Among subjects alive at the end of year 1, those with a stable FVC were more likely to be alive at the end of year 2 than those whose FVC declined (hazard ratio [HR], 0.91 [95% CI, 0.87-0.94] and HR, 0.71 [95% CI, 0.62 0.78], respectively). CONCLUSIONS: PFT decline predicts early mortality, but not future declines in physiology, regardless of time since diagnosis. PMID- 24231812 TI - A feature-based morphing methodology for computationally modeled biological structures applied to left atrial fiber directions. AB - To properly simulate the behavior of biological structures through computer modeling, there exists a need to describe parameters that vary locally. These parameters can be obtained either from literature or from experimental data and they are often assigned to regions in the model as lumped values. Furthermore, parameter values may be obtained on a representative case and may not be available for each specific modeled organ. We describe a semiautomated technique to assign detailed maps of local tissue properties to a computational model of a biological structure. We applied the method to the left atrium of the heart. The orientation of myocytes in the tissue as obtained from histologic analysis was transferred to the 3D model of a porcine left atrium. Finite element method (FEM) dynamic simulations were performed by using an isotropic, neo-Hookean, constitutive model first, then adding an anisotropic, cardiomyocyte oriented, Fung-type component. Results showed higher stresses for the anisotropic material model corresponding to lower stretches in the cardiomyocyte directions. The same methodology can be applied to transfer any map of parameters onto a discretized finite element model. PMID- 24231813 TI - Localization of viscous behavior and shear energy dissipation in articular cartilage under dynamic shear loading. AB - Though remarkably robust, articular cartilage becomes susceptible to damage at high loading rates, particularly under shear. While several studies have measured the local static and steady-state shear properties of cartilage, it is the local viscoelastic properties that determine the tissue's ability to withstand physiological loading regimens. However, measuring local viscoelastic properties requires overcoming technical challenges that include resolving strain fields in both space and time and accurately calculating their phase offsets. This study combined recently developed high-speed confocal imaging techniques with three approaches for analyzing time- and location-dependent mechanical data to measure the depth-dependent dynamic modulus and phase angles of articular cartilage. For sinusoidal shear at frequencies f = 0.01 to 1 Hz with no strain offset, the dynamic shear modulus |G*| and phase angle delta reached their minimum and maximum values (respectively) approximately 100 MUm below the articular surface, resulting in a profound focusing of energy dissipation in this narrow band of tissue that increased with frequency. This region, known as the transitional zone, was previously thought to simply connect surface and deeper tissue regions. Within 250 MUm of the articular surface, |G*| increased from 0.32 +/- 0.08 to 0.42 +/- 0.08 MPa across the five frequencies tested, while delta decreased from 12 deg +/- 1 deg to 9.1 deg +/- 0.5 deg. Deeper into the tissue, |G*| increased from 1.5 +/- 0.4 MPa to 2.1 +/- 0.6 MPa and delta decreased from 13 deg +/- 1 deg to 5.5 deg +/- 0.2 deg. Viscoelastic properties were also strain-dependent, with localized energy dissipation suppressed at higher shear strain offsets. These results suggest a critical role for the transitional zone in dissipating energy, representing a possible shift in our understanding of cartilage mechanical function. Further, they give insight into how focal degeneration and mechanical trauma could lead to sustained damage in this tissue. PMID- 24231814 TI - Optimized design of an instrumented spatial linkage that minimizes errors in locating the rotational axes of the tibiofemoral joint: a computational analysis. AB - An accurate method to locate of the flexion-extension (F-E) axis and longitudinal rotation (LR) axis of the tibiofemoral joint is required to accurately characterize tibiofemoral kinematics. A method was recently developed to locate these axes using an instrumented spatial linkage (ISL) (2012, "On the Estimate of the Two Dominant Axes of the Knee Using an Instrumented Spatial Linkage," J. Appl. Biomech., 28(2), pp. 200-209). However, a more comprehensive error analysis is needed to optimize the design and characterize the limitations of the device before using it experimentally. To better understand the errors in the use of an ISL in finding the F-E and LR axes, our objectives were to (1) develop a method to computationally determine the orientation and position errors in locating the F-E and LR axes due to transducer nonlinearity and hysteresis, ISL size and attachment position, and the pattern of applied tibiofemoral motion, (2) determine the optimal size and attachment position of an ISL to minimize these errors, (3) determine the best pattern of pattern of applied motion to minimize these errors, and (4) examine the sensitivity of the errors to range of flexion and internal-external (I-E) rotation. A mathematical model was created that consisted of a virtual "elbow-type" ISL that measured motion across a virtual tibiofemoral joint. Two orientation and two position errors were computed for each axis by simulating the axis-finding method for 200 iterations while adding transducer errors to the revolute joints of the virtual ISL. The ISL size and position that minimized these errors were determined from 1080 different combinations. The errors in locating the axes using the optimal ISL were calculated for each of three patterns of motion applied to the tibiofemoral joint, consisting of a sequential pattern of discrete tibiofemoral positions, a random pattern of discrete tibiofemoral positions, and a sequential pattern of continuous tibiofemoral positions. Finally, errors as a function of range of flexion and I-E rotation were determined using the optimal pattern of applied motion. An ISL that was attached to the anterior aspect of the knee with 300-mm link lengths had the lowest maximum error without colliding with the anatomy of the joint. A sequential pattern of discrete tibiofemoral positions limited the largest orientation or position error without displaying large bias error. Finally, the minimum range of applied motion that ensured all errors were below 1 deg or 1 mm was 30 deg flexion with +/-15 deg I-E rotation. Thus a method for comprehensive analysis of error when using this axis-finding method has been established, and was used to determine the optimal ISL and range of applied motion; this method of analysis could be used to determine the errors for any ISL size and position, any applied motion, and potentially any anatomical joint. PMID- 24231815 TI - Determination and modeling of the inelasticity over the length of the porcine carotid artery. AB - The study of the mechanical properties of swine carotids has clinical relevance because it is important for the appropriate design of intravascular devices in the animal trial phases. The inelastic properties of porcine carotid tissue were investigated. Experimental uniaxial cyclic tests were performed along the longitudinal and circumferential directions of vessels. The work focused on the determination, comparison, and constitutive modeling of the softening properties and residual stretch set of the swine carotid artery over long stretches and stress levels in both proximal and distal regions. It was observed that the residual strain depends on the maximum stretch in the previous load cycle. The strain was higher for distal than for proximal samples and for circumferential than for longitudinal samples. In addition, a pseudoelastic model was used to reproduce the residual stretch and softening behavior of the carotid artery. The model presented a good approximation of the experimental data. The results demonstrate that the final results in animal trial studies could be affected by the location studied along the length of the porcine carotid. PMID- 24231816 TI - Comparative study on tube-load modeling of arterial hemodynamics in humans. AB - In this paper, we assess the validity of two alternative tube-load models for describing the relationship between central aortic and peripheral arterial blood pressure (BP) waveforms in humans. In particular, a single-tube (1-TL) model and a serially connected two-tube (2-TL) model, both terminated with a Windkessel load, are considered as candidate representations of central aortic-peripheral arterial path. Using the central aortic, radial and femoral BP waveform data collected from eight human subjects undergoing coronary artery bypass graft with cardiopulmonary bypass procedure, the fidelity of the tube-load models was quantified and compared with each other. Both models could fit the central aortic radial and central aortic-femoral BP waveform pairs effectively. Specifically, the models could estimate pulse travel time (PTT) accurately, and the model derived frequency response was also close to the empirical transfer function estimate obtained directly from the central aortic and peripheral BP waveform data. However, 2-TL model was consistently superior to 1-TL model with statistical significance as far as the accuracy of the central aortic BP waveform was concerned. Indeed, the average waveform RMSE was 2.52 mmHg versus 3.24 mmHg for 2-TL and 1-TL models, respectively (p < 0.05); the r2 value between measured and estimated central aortic BP waveforms was 0.96 and 0.93 for 2-TL and 1-TL models, respectively (p < 0.05). We concluded that the tube-load models considered in this paper are valid representations that can accurately reproduce central aortic-radial/femoral BP waveform relationships in humans, although the 2 TL model is preferred if an accurate central aortic BP waveform is highly desired. PMID- 24231817 TI - Tendon fascicles exhibit a linear correlation between Poisson's ratio and force during uniaxial stress relaxation. AB - The underlying mechanisms for the viscoelastic behavior of tendon and ligament tissue are poorly understood. It has been suggested that both a flow-dependent and flow-independent mechanism may contribute at different structural levels. We hypothesized that the stress relaxation response of a single tendon fascicle is consistent with the flow-dependent mechanism described by the biphasic theory (Armstrong et al., 1984, "An Analysis of the Unconfined Compression of Articular Cartilage," ASME J. Biomech. Eng., 106, pp. 165-173). To test this hypothesis, force, lateral strain, and Poisson's ratio were measured as a function of time during stress relaxation testing of six rat tail tendon fascicles from a Sprague Dawley rat. As predicted by biphasic theory, the lateral strain and Poisson's ratio were time dependent, a large estimated volume loss was seen at equilibrium and there was a linear correlation between the force and Poisson's ratio during stress relaxation. These results suggest that the fluid dependent mechanism described by biphasic theory may explain some or all of the apparent viscoelastic behavior of single tendon fascicles. PMID- 24231818 TI - Left ventricular pressure gating in ovine cardiac studies: a software-based method. AB - Cardiac imaging using magnetic resonance requires a gating signal in order to compensate for motion. Human patients are routinely scanned using an electrocardiogram (ECG) as a gating signal during imaging. However, we found that in sheep the ECG is not a reliable method for gating. We developed a software based method that allowed us to use the left ventricular pressure (LVP) as a reliable gating signal. By taking the time derivative of the LVP (dP/dt), we were able to start imaging at both end-diastole for systolic phase images, and end systole for diastolic phase images. We also used MR tissue tagging to calculate 3D strain information during diastole. Using the LVP in combination with our digital circuit provided a reliable and time efficient method for ovine cardiac imaging. Unlike the ECG signal the left ventricular pressure was a clean signal and allowed for accurate, nondelay based triggering during systole and diastole. PMID- 24231819 TI - A model of the recruitment-derecruitment and volume of lung units in an excised lung as it is inflated-deflated between minimum and maximum lung volume. AB - The role of the recruitment-derecruitment of small structures in the lung (lung units) as the lung increases and decreases in volume has been debated. The objective of this study was to develop a model to estimate the change in the number and volume of open lung units as an excised lung is inflated-deflated between minimum and maximum lung volume. The model was formulated based on the observation that the compliance of the slowly changing quasi-static pressure volume (P-V) curve of an excised rat lung can differ from the compliance of a faster changing small sinusoidal pressure volume perturbations superimposed on the curve. In those regions of the curve where differences in compliance occur, the lung tissue properties exhibit nonlinear characteristics, which cannot be linearized using "incremental" or "small signal" analysis. The model attributes the differences between the perturbation and quasi-static compliance to an additional nonlinear compliance term that results from the sequential opening and closing of lung units. Using this approach, it was possible to calculate the normalized average volume and the normalized number of open units as the lung is slowly inflated-deflated. Results indicate that the normalized average volume and the normalized number of open units are not linearly related to normalized lung volume, and at equal lung volumes the normalized number of open units is greater and the normalized average lung unit volume is smaller during lung deflation when compared to lung inflation. In summary, a model was developed to describe the recruitment-derecruitment process in excised lungs based on the differences between small signal perturbation compliance and quasi-static compliance. Values of normalized lung unit volume and the normalized number of open lung units were shown to be nonlinear functions of both transpulmonary pressure and normalized lung volume. PMID- 24231820 TI - Hydrodynamic modeling of targeted magnetic-particle delivery in a blood vessel. AB - Since the flow of a magnetic fluid could easily be influenced by an external magnetic field, its hydrodynamic modeling promises to be useful for magnetically controllable delivery systems. It is desirable to understand the flow fields and characteristics before targeted magnetic particles arrive at their destination. In this study, we perform an analysis for the effects of particles and a magnetic field on biomedical magnetic fluid flow to study the targeted magnetic-particle delivery in a blood vessel. The fully developed solutions of velocity, flow rate, and flow drag are derived analytically and presented for blood with magnetite nanoparticles at body temperature. Results reveal that in the presence of magnetic nanoparticles, a minimum magnetic field gradient (yield gradient) is required to initiate the delivery. A magnetic driving force leads to the increase in velocity and has enhancing effects on flow rate and flow drag. Such a magnetic driving effect can be magnified by increasing the particle volume fraction. PMID- 24231821 TI - In vitro pulsatility analysis of axial-flow and centrifugal-flow left ventricular assist devices. AB - Recently, continuous-flow ventricular assist devices (CF-VADs) have supplanted older, pulsatile-flow pumps, for treating patients with advanced heart failure. Despite the excellent results of the newer generation devices, the effects of long-term loss of pulsatility remain unknown. The aim of this study is to compare the ability of both axial and centrifugal continuous-flow pumps to intrinsically modify pulsatility when placed under physiologically diverse conditions. Four VADs, two axial- and two centrifugal-flow, were evaluated on a mock circulatory flow system. Each VAD was operated at a constant impeller speed over three hypothetical cardiac conditions: normo-tensive, hypertensive, and hypotensive. Pulsatility index (PI) was compared for each device under each condition. Centrifugal-flow devices had a higher PI than that of axial-flow pumps. Under normo-tension, flow PI was 0.98 +/- 0.03 and 1.50 +/- 0.02 for the axial and centrifugal groups, respectively (p < 0.01). Under hypertension, flow PI was 1.90 +/- 0.16 and 4.21 +/- 0.29 for the axial and centrifugal pumps, respectively (p = 0.01). Under hypotension, PI was 0.73 +/- 0.02 and 0.78 +/- 0.02 for the axial and centrifugal groups, respectively (p = 0.13). All tested CF-VADs were capable of maintaining some pulsatile-flow when connected in parallel with our mock ventricle. We conclude that centrifugal-flow devices outperform the axial pumps from the basis of PI under tested conditions. PMID- 24231822 TI - Combined in vivo/in vitro method to study anteriomedial bundle strain in the anterior cruciate ligament using a dynamic knee simulator. AB - The mechanism of noncontact anterior cruciate ligament (ACL) injury is not well understood. It is partly because previous studies have been unable to relate dynamic knee muscle forces during sports activities such as landing from a jump to the strain in the ACL. We present a combined in vivo/in vitro method to relate the muscle group forces to ACL strain during jump-landing using a newly developed dynamic knee simulator. A dynamic knee simulator system was designed and developed to study the sagittal plane biomechanics of the knee. The simulator is computer controlled and uses six powerful electromechanical actuators to move a cadaver knee in the sagittal plane and to apply dynamic muscle forces at the insertion sites of the quadriceps, hamstring, and gastrocnemius muscle groups and the net moment at the hip joint. In order to demonstrate the capability of the simulator to simulate dynamic sports activities on cadaver knees, motion capture of a live subject landing from a jump on a force plate was performed. The kinematics and ground reaction force data obtained from the motion capture were input into a computer based musculoskeletal lower extremity model. From the model, the force-time profile of each muscle group across the knee during the movement was extracted, along with the motion profiles of the hip and ankle joints. This data was then programmed into the dynamic knee simulator system. Jump-landing was simulated on a cadaver knee successfully. Resulting strain in the ACL was measured using a differential variable reluctance transducer (DVRT). Our results show that the simulator has the capability to accurately simulate the dynamic sagittal plane motion and the dynamic muscle forces during jump-landing. The simulator has high repeatability. The ACL strain values agreed with the values reported in the literature. This combined in vivo/in vitro approach using this dynamic knee simulator system can be effectively used to study the relationship between sagittal plane muscle forces and ACL strain during dynamic activities. PMID- 24231823 TI - [Computed tomography guidance: fluoroscopy and more]. AB - Although ultrasound and magnetic resonance imaging are competitive imaging modalities for the guidance of needle-based interventions, computed tomography (CT) is the only modality suitable for image-guided interventions in all regions of the body, including the lungs and bone. The ongoing technical development of CT involves accelerated image acquisition, significantly improved spatial resolution, CT scanners with an extended gantry diameter, acceleration of the procedure through joystick control of relevant functions of interventional CT by the interventional radiologist and tube current modulation to protect the hands of the examiner and radiosensitive organs of the patient. CT fluoroscopy can be used as a real-time method (the intervention is monitored under continuous CT fluoroscopy) or as a quick check method (repeated acquisitions of individual CT fluoroscopic images after each change of needle or table position). For the two approaches, multislice CT fluoroscopy (MSCTF) technique with wide detectors is particularly useful because even in the case of needle deviation from the center slice the needle tip is simultaneously visualised in the neighboring slices. With the aid of this technique a precise placement of interventional devices is possible even in angled access routes and in the presence of pronounced respiratory organ movements. As the reduction of CT fluoroscopy time significantly reduces radiation exposure for the patient and staff, the combination of a quick check technique and a low milliampere technique with multislice CT fluoroscopy devices is advantageous. PMID- 24231824 TI - [The museum of the German Society for Ultrasound in Medicine]. PMID- 24231828 TI - Bringing neurosurgical and neurological care to the world. PMID- 24231826 TI - [Cardiac magnetic resonance imaging: from imaging to diagnosis]. AB - Cardiac magnetic resonance imaging (CMR) has evolved over the past 20 years from a research-based imaging modality to an indispensable routine procedure in cardiac diagnostics. In addition to the morphological representation of cardiac anatomy, whereby only noninvasive multidetector computed tomography (MDCT) is superior, another strength of CMR is the assessment of cardiac function and tissue differentiation. This requires that the radiologist performing the examination and analyzing the results has good knowledge of cardiac and thoracic anatomy and a detailed knowledge of the various cardiovascular diseases, hemodynamics, and pathophysiology. CMR reliably allows determination of a range of easy to determine quantitative parameters such as ventricular ejection fraction and also the valvular regurgitation fraction, which allows objective assessment of cardiac function. Especially the possibility to differentiate inflamed, viable, and ischemic tissue using adenosine stress MRI in the last 10 years has led to routine use of CMR. Even compared to competing nuclear medicine procedures, CMR is important for treatment decision-making and for prognosis estimation, thus, making it an indispensable component of cardiovascular diagnostics. PMID- 24231829 TI - Murine models of inflammatory bowel disease (IBD): challenges of modeling human disease. AB - Animal models of human disease are a critical tool in both basic research and drug development. The results of preclinical efficacy studies often inform progression of therapeutic candidates through the drug development pipeline; however, the extent to which results in inflammatory bowel disease (IBD) models predict human drug response is an ongoing concern. This review discusses how murine models are currently being used in IBD research. We focus on the considerations and caveats for commonly used models in preclinical efficacy studies and discuss the value of models that utilize specific pathogenic pathways of interest rather than model all aspects of human disease. PMID- 24231830 TI - Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not by aquaporin-1: 17O JJVCPE MRI study in knockout mice. AB - Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow-Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo. The results clearly indicate that water influx into the CSF is regulated by AQP-4, and not by AQP-1, strongly supporting the Oreskovic and Klarica hypothesis. PMID- 24231831 TI - Endogenous auditory frequency-based attention modulates electroencephalogram based measures of obligatory sensory activity in humans. AB - Auditory selective attention is the ability to enhance the processing of a single sound source, while simultaneously suppressing the processing of other competing sound sources. Recent research has addressed a long-running debate by showing that endogenous attention produces effects on obligatory sensory responses to continuous and competing auditory stimuli. However, until now, this result has only been shown under conditions where the competing stimuli differed in both their frequency characteristics and, importantly, their spatial location. Thus, it is unknown whether endogenous selective attention based only on nonspatial features modulates obligatory sensory processing. Here, we investigate this issue using a diotic paradigm, such that competing auditory stimuli differ in frequency, but had no separation in space. We find a significant effect of attention on electroencephalogram-based measures of obligatory sensory processing at several poststimulus latencies. We discuss these results in terms of previous research on feature-based attention and by comparing our findings with the previous work using stimuli that differed both in terms of spatial and frequency based characteristics. PMID- 24231832 TI - Bioaccumulation and histopathological alteration of total lead in selected fishes from Manila Bay, Philippines. AB - This study aims to assess the bioaccumulation of total lead and the effect of heavy metal on the muscles of fish obtained in the coastal lagoon of the Manila Bay. Fish species muscles were assessed for lead concentrations and were examined for histological alterations. Results showed that lead bioaccumulation in the muscles, and a degree of disintegration in the muscle fibers of all the fish examined were found. PMID- 24231833 TI - Henoch-Schonlein purpura (HSP) and high-dose immunoglobulin treatment in patient with familiar prostatic adenocarcinoma. AB - A 52-y old man was admitted to our Department because of abdominal pains and diarrhea with fresh blood, with concomitant purpura over the whole body and edema of the both tarsal joints. The medical history of the patient included skin changes of similar character identified once 10-12 y before. The family history revealed prostate cancer (brother and father) and pulmonary carcinoma (mother and mother's sister). An administration of immunoglobulins in the course of HSP is a non-standard clinical procedure and in case of our patient--clinically effective. In the literature, we have found only few articles about intravenous immunoglobulin treatment for acute, adult-onset HSP and only one article about GI bleeding from colonic ecchymoses in HSP. In these cases HSP wasn't associated with prostate cancer. In the first article, authors had seen dramatic responses to intravenous immunoglobulin, like in the case presented by us. IV-IG acts as an immunomodulator by suppression of antibody production, Fc-receptor blockade and anti-idiotypic reaction. In our case, the last two mechanisms could be perceived as favorable effects of IV-IG. PMID- 24231834 TI - Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit(r)): a pilot, registry evaluation. AB - AIM: The aim of this supplement study was to evaluate French oak wood extract (Robuvit(r), Horphag Research Ltd) used as a supplement in association with a defined management plan for chronic fatigue syndrome (CFS) in healthy subjects with CFS, a condition that has, so far, no specific treatment or management standards. METHODS: Robuvit(r) is a new proprietary and exclusive extract of oak wood with important antoxidant actions. The dosage of the supplementation was 200 mg/day for at least 6 months. The CFS questionnaire and the Brief Mood Introspection Scale (BMIS) questionnaire were used to evaluate mood variations associated with CFS patients. The CFS form includes an analogue scale to record the variations of single symptoms with a score range of 0-10. At inclusion into the registry study, at least 5 symptoms were present. All subjects (age range 35 44; BMI range 24-26) with CFS were tested for oxidative stress: 61 out of 91 subjects had an increased value of oxidative stress. The BMIS scale evaluating mood changes in time was also used. The evaluation was repeated at 3 and 6 months. RESULTS: Out of 91 eligible subjects with CFS, 48 subjects (31 with increased oxidative stress) were accepted as part of the supplement registry study using Robuvit; 43 (30 with increased oxidative stress) were accepted as controls using only the management plan. In the Robuvit(r) group there were 3 drop outs; also 3 controls were lost. Oxidative stress was increased in 64.58% of subjects that used Robuvit and in 69.7% of controls. The average values of oxidative stress were expressed for the whole group. The average follow up was 199.3;9.2 days in the Robuvit group and 202.2;5.5 in the control group with a minimum of 6 months. Considering variations in oxidative stress, there was no significant average change in controls, but a significant decrease from the initial values was observed in Robuvit subjects after 3 and 6 months. The CFS questionnaire variations in score indicated that there was a significant improvement for most symptoms after 3 and 6 months in the Robuvit group. Positive variations were also present in controls, indicating the positive effect of an increased attention to CFS. The improvement in signs/symptoms was significantly more valuable in subjects using the oak wood extract considering the main 8 symptoms and the accessory symptoms. Considering the BMIS variations, the totals for positive and negative items were significantly more favourable for Robuvit subjects. Overall mood evaluation in the oak wood extract group improved from an inclusion average of -6.93;2.1 to +4.32;2.6 at 6 months; in contrast it changed from -6.5;2.5 to -3.4;1.5 in controls. No side effects were observed during the supplementation with Robuvit. The compliance was optimal with 93% of the capsules correctly used. CONCLUSION: This promising pilot supplement registry study indicates a new opportunity of management for these difficult and often neglected patients. Correlation between oxidative stress and CFS have to be better explored. PMID- 24231835 TI - Active surveillance of the adolescent with varicocele: predicting semen outcomes from ultrasound. AB - PURPOSE: We hypothesized that active surveillance of the adolescent varicocele is not associated with a high prevalence of suboptimal semen analysis and that patients with abnormal semen analysis have smaller testicular volumes and larger volume differentials. MATERIALS AND METHODS: We conducted an institutional review board approved retrospective cohort study of adolescents with a clinically detected varicocele. Patients were initially observed by serial scrotal ultrasound evaluating testicular size and differential. Semen analysis was routinely collected in Tanner V cases, around age 18 years. Prevalence of normal semen analysis parameters was calculated, and logistic regression was used to model the ability of age at presentation and testicular volume parameters to predict a normal semen analysis. RESULTS: A cohort of 73 patients underwent surveillance with a mean +/- SD age at presentation of 15.5 +/- 2.3 years. Median followup was 2.7 years, during which time subjects underwent a median of 3 scrotal ultrasounds. A low total motile count was found in 48 patients (66%). Neither age at presentation nor testicular volume differential could predict normal semen volume, density, sperm motility or total motile count. Total testicular volume from the final ultrasound predicted total motile count (p = 0.008). However, the collective observations of volume during the entire period of surveillance could not predict total motile count (p = 0.847). CONCLUSIONS: There is a high prevalence of suboptimal semen analysis in adolescents with a varicocele who are followed with active surveillance. Total testicular volume can predict total motile count at the end of adolescence but not throughout. PMID- 24231836 TI - Lower urinary tract symptoms in the elderly male: choosing wisely. PMID- 24231837 TI - A phase 2, randomized, double-blind, efficacy and safety study of oxybutynin vaginal ring for alleviation of overactive bladder symptoms in women. AB - PURPOSE: We evaluated the efficacy and safety of a once monthly oxybutynin vaginal ring in women with overactive bladder. MATERIALS AND METHODS: This randomized, multicenter, double-blind, 12-week phase 2 study compared oxybutynin vaginal ring (4 or 6 mg daily) to a placebo vaginal ring in women with well defined overactive bladder symptoms. The primary efficacy variable was the change from baseline to week 12 in the total weekly number of incontinence episodes (stress and urge). Safety was measured in terms of treatment emergent adverse events, laboratory, physical, gynecologic examinations, electrocardiogram and vital signs. RESULTS: After a 3-week post-randomization placebo run-in phase (sample size 720) 445 women entered the treatment phase (safety population). Of these women 323 met all 3 overactive bladder specific baseline characteristics of 10 or more urinary urge incontinence episodes weekly, urinary frequency 8 or more voids per 24 hours and voided volume 3 L or less per 24 hours) (analysis population). Women treated with 4 and 6 mg daily oxybutynin vaginal ring had significantly fewer incontinence episodes weekly (p = 0.036 and p = 0.018, respectively), lower daily urinary frequency (p = 0.014, p = 0.002) and a higher proportion had no incontinence episodes at week 12 (p = 0.026, p = 0.027) compared with placebo. The change in severity of urgency and voided volume was similar for all groups (p >0.05). Except for a higher incidence of dry mouth and urinary tract infections that were not always culture confirmed, the oxybutynin vaginal ring was well tolerated and had a safety profile similar to that of the placebo vaginal ring. CONCLUSIONS: The oxybutynin vaginal ring appears to be an effective and safe once monthly treatment option for women with overactive bladder characterized primarily by urinary urge incontinence that merits further evaluation in a phase 3 study. PMID- 24231838 TI - Pediatric urethral catheter consultations: understanding driving factors. AB - PURPOSE: Pediatric urethral catheterization is often straightforward. However, it can be challenging and may require urological consultation. Possible critical factors are patient anatomy and comorbidities, and insertion technique. To better understand pediatric catheter consultations, we reviewed our experience. MATERIALS AND METHODS: All pediatric catheter consultations between July 2009 and June 2012 were identified. A retrospective review was then performed, focusing on demographics, reasons for consultation and difficulty of catheter placement. The 4 categories of difficulty noted were easy, challenging, extremely difficult and could not be placed. Patients were excluded from analysis if catheter placement was not needed, the consultation was for a catheterizable stoma or they were status post urological surgery. Statistical analyses were performed to evaluate associations between patient factors and difficulty of placement. RESULTS: A total of 93 consultations were identified, of which 57% were inpatient, 28% intraoperative and 15% other source. Of the inpatient consultations 75% were from an intensive care unit, the majority (80%) of which were for catheter placement, with the remainder for removal, nondraining catheter, trauma or other. After exclusions 65 patients remained, of whom 80% were male and 32% had a urological comorbidity. By difficulty level 69.2% of cases were easy, 15.4% were challenging, 9.2% were extremely difficult and 6.2% could not be placed. Location of consult, gender, urological comorbidity and history of prematurity were not significantly associated with difficult catheter placement. CONCLUSIONS: Pediatric catheter consultations are largely straightforward. Comorbidities do not significantly impact catheter placement. Correct catheter technique may be more important than patient comorbidities, giving us a basis to shape catheter insertion training within pediatric hospitals. PMID- 24231840 TI - New renal cell carcinomas in the International Society of Urological Pathology Vancouver classification of renal neoplasia. PMID- 24231841 TI - Crossed fused renal ectopia. PMID- 24231842 TI - New contralateral vesicoureteral reflux-is it double trouble? PMID- 24231843 TI - 5-Year outcome of a randomized prospective study comparing bacillus Calmette Guerin with epirubicin and interferon-alpha2b in patients with T1 bladder cancer. AB - PURPOSE: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha2b in the treatment of patients with T1 bladder cancer. MATERIALS AND METHODS: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. RESULTS: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. CONCLUSIONS: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy. PMID- 24231844 TI - Differentiating between symptomatic and asymptomatic urinary tract infections using genetic tools. PMID- 24231845 TI - Systematic review and meta-analysis of perioperative and oncologic outcomes of laparoscopic cryoablation versus laparoscopic partial nephrectomy for the treatment of small renal tumors. AB - PURPOSE: For the minimally invasive treatment of small renal tumors, laparoscopic cryoablation has emerged as an alternative procedure to minimally invasive partial nephrectomy (laparoscopic, robot-assisted laparoscopic) for selected patients, but there are still limited data regarding its safety and oncologic efficacy. We compare perioperative and oncologic outcomes of laparoscopic cryoablation and laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy. MATERIALS AND METHODS: We searched the literature published until September 2013 from MEDLINE(r), Web of Science(r) and major conference proceedings. We included studies comparing laparoscopic cryoablation and laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy if they reported oncologic or perioperative outcomes. RESULTS: Overall 13 retrospective, nonrandomized, observational studies met our inclusion criteria. According to the modified NOS (Newcastle-Ottawa Scale) 7 studies (53%) were considered to be of higher quality. Compared with laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy, laparoscopic cryoablation was associated with significantly shorter operative times (weighted mean difference [WMD] 35.45 minutes), lower estimated blood loss (WMD 130.11 ml), shorter length of stay (WMD 1.22 days), and a lower risk of total (RR 1.82), urological (RR 1.99) and nonurological complications (RR 2.33). Patients undergoing laparoscopic cryoablation had a significantly increased risk of local (RR 9.39) and metastatic tumor progression (RR 4.68). CONCLUSIONS: This analysis provides fair evidence that oncologic outcomes are substantially worse for laparoscopic cryoablation than for laparoscopic partial nephrectomy/robot assisted laparoscopic partial nephrectomy, but laparoscopic cryoablation may be associated with improved perioperative outcomes. Therefore, surgical resection may be encouraged in the majority of cases. Balancing cancer control with the risk of perioperative complications is crucial for patient counseling and selection of the appropriate procedure. Prospective, randomized controlled studies with long-term followup are needed to confirm our findings. PMID- 24231847 TI - Endovascular treatment of 300 consecutive middle cerebral artery aneurysms: clinical and radiologic outcomes. AB - BACKGROUND AND PURPOSE: There is controversy as to the best mode of treating MCA aneurysms. We report the results of a large endovascular series of patients treated at our center. MATERIALS AND METHODS: This study was a retrospective analysis of a prospectively acquired data base. All patients with saccular MCA aneurysms treated between November 1996 and June 2012 were included. World Federation of Neurosurgical Societies grade, aneurysm site, size, and aneurysm neck size were recorded, along with clinical outcome assessed with the Glasgow Outcome Scale and radiographic occlusion assessed with the Raymond classification at 6 months and 2.5 years. RESULTS: A total of 295 patients with 300 MCA aneurysms were treated including 244 ruptured aneurysms (80.7%). The technical failure rate was 4.3% (13 patients). Complete occlusion or neck remnant was achieved in 264 (91.4%). Complications included rupture in 15 patients (5%), thromboembolism in 17 patients (5.7%), and early rebleeding in 3 patients (1%). Overall permanent procedural-related morbidity and mortality were seen in 12 patients (7.8%). Of the ruptured aneurysms, 189 (79.4%) had a favorable clinical outcome (Glasgow Outcome Scale score, 4-5). A total of 33 patients (13.6%) died. On initial angiographic follow-up, aneurysm remnant was seen in 18 aneurysms (8.1%). A total of 13 patients (4.3%) were re-treated. CONCLUSIONS: Our experience demonstrates that endovascular treatment of MCA aneurysms has an acceptable safety profile with low rates of technical failure and re-treatment. Therefore, coiling is acceptable as the primary treatment of MCA aneurysms. PMID- 24231848 TI - Diffusional kurtosis imaging of the developing brain. AB - BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an extension of DTI but includes non-Gaussian diffusion effects, allowing more comprehensive characterization of microstructural changes during brain development. Our purpose was to use diffusional kurtosis imaging to measure age-related microstructural changes in both the WM and GM of the developing human brain. MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in 59 subjects ranging from birth to 4 years 7 months of age. Diffusion metrics, fractional anisotropy, and mean kurtosis were collected from VOIs within multiple WM and GM structures and subsequently analyzed with respect to age. Diffusional kurtosis tractography images at various stages of development were also generated. RESULTS: Fractional anisotropy and mean kurtosis both showed age-related increases in all WM regions, reflecting progression of diffusional anisotropy throughout development, predominantly in the first 2 years of life (eg, 70% and 157% increase in fractional anisotropy and mean kurtosis, respectively, from birth to 2 years for the splenium). However, mean kurtosis detected continued microstructural changes in WM past the fractional anisotropy plateau, accounting for more delayed isotropic changes (eg, 90% of maximum fractional anisotropy was reached at 5 months, whereas 90% of maximum mean kurtosis occurred at 18 months for the external capsule). Mean kurtosis may also provide greater characterization of GM maturation (eg, the putamen showed no change in fractional anisotropy but an 81% change in mean kurtosis from birth to 4 years 7 months). CONCLUSIONS: Mean kurtosis detects significant microstructural changes consistent with known patterns of brain maturation. In comparison with fractional anisotropy, mean kurtosis may offer a more comprehensive evaluation of age-related microstructural changes in both WM and GM and is potentially a valuable technique for studying brain development. PMID- 24231849 TI - Imaging findings in auto-atticotomy. AB - BACKGROUND AND PURPOSE: An acquired attic cholesteatoma may spontaneously drain externally into the external auditory canal, leaving a cavity in the attic with the shape of the original cholesteatoma but now filled with air, a phenomenon referred to as "nature's atticotomy" or auto-atticotomy. We describe and quantify the CT appearance of the auto-atticotomy cavity as it pertains to the appearance of the scutum and the lateral attic wall. MATERIALS AND METHODS: Twenty-one patients with erosion of the scutum and loss of the lower attic wall on MDCT were identified during a 5-year span. Images were assessed for measureable widening of the space between the ossicles and the lower lateral attic wall in the axial and coronal planes. Three measurements of the lateral attic were made on the axial images. Findings were compared with the same measurements in 20 control subjects. RESULTS: The 21 patients had a characteristic blunting of the scutum with loss of the lower lateral attic wall and widening of the lateral attic, consistent with an auto-atticotomy. There was a statistically significant (P < .001) widening of the lateral attic dimensions in the axial plane in the patients with auto atticotomy. CONCLUSIONS: Spontaneously evacuated cholesteatoma may mimic a surgical atticotomy on MDCT. Scutal erosion and attic enlargement with a smoothly contoured bony remodeling of the lower lateral attic wall in a patient with no history of surgery suggest that a cholesteatoma was previously present and spontaneously drained. PMID- 24231850 TI - Accountable care organizations: what radiologists should know. PMID- 24231851 TI - Genetics of Huntington disease. PMID- 24231852 TI - Validation and initial application of a semiautomatic aneurysm measurement software: a tool for assessing volumetric packing attenuation. AB - BACKGROUND AND PURPOSE: Precise aneurysm measurements and volume embolization ratios are essential for long-term durability of endovascular coil embolization. We evaluated the accuracy of newly developed semiautomatic cerebral aneurysm measurement software, NeuroVision, and explored the value of volume embolization ratio in the prediction of re-treatment. MATERIALS AND METHODS: We compared software-derived volume measurements of 4 silicone aneurysm models with those calculated with an approximation formula and ground truth values (validation study). We used NeuroVision to retrospectively evaluate outcomes of 100 unruptured aneurysms (97 patients) treated with embolization (clinical study). Aneurysm size (height, width, and neck), volume, and volume embolization ratios were calculated for 3 groups (stable, recanalization, and re-treatment) and were compared. RESULTS: This validation study illustrated higher accuracy of NeuroVision in computing aneurysm volume compared with an approximation formula: percentage absolute errors were 4.50% +/- 3.18% and 23.07% +/- 17.60%, with maximal percentage absolute errors of 8.99% and 45.63%, respectively. Of 100 unruptured aneurysms, 20 recanalized and 12 were re-treated. Average volume embolization ratios of stable and re-treated aneurysms were 24.88% +/- 5.91% and 20.50% +/- 4.06%, respectively (P <= .01). The optimal volume embolization ratio cutoff point for re-treatment was < 19.15%, at which the Youden index was 0.50 (sensitivity, 58.33%; specificity, 87.50%; area under the receiver operating characteristic curve, 0.74). CONCLUSIONS: The NeuroVision software provided accurate aneurysm volume measurements and may be a useful standardized tool to measure aneurysm size and volume, especially for multicenter clinical studies. Volume embolization ratio may be a valuable predictor of aneurysm occlusion changes. PMID- 24231853 TI - Temporal correlation between wall shear stress and in-stent stenosis after Wingspan stent in swine model. AB - BACKGROUND AND PURPOSE: A recent randomized clinical trial on intracranial atherosclerosis was discontinued because of the higher frequency of stroke and death in the angioplasty and stent placement group than in the medical treatment group. An in-depth understanding of the relationship between biologic responses and flow dynamics is still required to identify the current limitations of intracranial stent placement. MATERIALS AND METHODS: Five Wingspan stents were deployed in tapered swine ascending pharyngeal arteries. Temporal wall shear stress distributions and in-stent stenosis were evaluated at days 0, 7, 14, and 28 after stent placement. The physiologic role of wall shear stress was analyzed regarding its correlation with in-stent stenosis. RESULTS: In-stent stenosis reached a peak of nearly 40% at day 14 and decreased mainly at the distal stent segment until day 28. The wall shear stress demonstrated a characteristic pattern with time on the basis of the in-stent stenosis change. The wall shear stress gradient increased from the proximal to distal segment until day 14. At day 28, the trend was reversed dramatically, decreasing from the proximal to the distal segment. A significant correlation between the in-stent stenosis growth until day 14 and low wall shear stress values just after stent placement was detected. In stent stenosis regression between days 14 and 28 was also associated with the high wall shear stress values at day 14. CONCLUSIONS: These data suggest that the physiologic wall shear stress can control the biphasic in-stent stenosis change in tapered arteries. PMID- 24231854 TI - Mind the gap: impact of computational fluid dynamics solution strategy on prediction of intracranial aneurysm hemodynamics and rupture status indicators. AB - BACKGROUND AND PURPOSE: Computational fluid dynamics has become a popular tool for studying intracranial aneurysm hemodynamics, demonstrating success for retrospectively discriminating rupture status; however, recent highly refined simulations suggest potential deficiencies in solution strategies normally used in the aneurysm computational fluid dynamics literature. The purpose of the present study was to determine the impact of this gap. MATERIALS AND METHODS: Pulsatile flow in 12 realistic MCA aneurysms was simulated by using both high resolution and normal-resolution strategies. Velocity fields were compared at selected instants via domain-averaged error. We also compared wall shear stress fields and various reduced hemodynamic indices: cycle-averaged mean and maximum wall shear stress, oscillatory shear index, low shear area, viscous dissipation ratio, and kinetic energy ratio. RESULTS: Instantaneous differences in flow and wall shear stress patterns were appreciable, especially for bifurcation aneurysms. Linear regressions revealed strong correlations (R(2) > 0.9) between high-resolution and normal-resolution solutions for all indices except kinetic energy ratio (R(2) = 0.25) and oscillatory shear index (R(2) = 0.23); however, for most indices, the slopes were significantly <1, reflecting a pronounced underestimation by the normal-resolution simulations. Some high-resolution simulations were highly unstable, with fluctuating wall shear stresses reflected by the poor oscillatory shear index correlation. CONCLUSIONS: Typical computational fluid dynamics solution strategies may ultimately be adequate for augmenting rupture risk assessment on the basis of certain highly reduced indices; however, they cannot be relied on for predicting the magnitude and character of the complex biomechanical stimuli to which the aneurysm wall may be exposed. This impact of the computational fluid dynamics solution strategy is likely greater than that for other modeling assumptions or uncertainties. PMID- 24231855 TI - Comparison of swallowing functions between brain tumor and stroke patients. AB - OBJECTIVE: To compare the swallowing functions according to the lesion locations between brain tumor and stroke patients. METHODS: Forty brain tumor patients and the same number of age-, lesion-, and functional status-matching stroke patients were enrolled in this study. Before beginning the swallowing therapy, swallowing function was evaluated in all subjects by videofluoroscopic swallowing study. Brain lesions were classified as either supratentorial or in-fratentorial. We evaluated the following: the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale, clinical dysphagia scale, functional dysphagia scale (FDS), penetration-aspiration scale (PAS), oral transit time, pharyngeal transit time, the presence of vallecular pouch residue, pyriform sinus residue, laryngopharyngeal incoordination, premature spillage, a decreased swal-lowing reflex, pneumonia, and the feeding method at discharge. RESULTS: The incidence of dysphagia was similar in brain tumor and stroke patients. There were no differences in the results of the various swallowing scales and other parameters between the two groups. When compared brain tumor patients with supratentorial lesions, brain tumor patients with infratentorial lesions showed higher propor-tion of dysphagia (p=0.01), residue (p<0.01), FDS (p<0.01), PAS (p<0.01), and lower ASHA NOMS (p=0.02) at initial evaluation. However, there was no significant difference for the swallowing functions between benign and malig-nant brain tumor patients. CONCLUSION: Swallowing function of brain tumor patients was not different from that of stroke patients according to matching age, location of lesion, and functional status. Similar to the stroke patients, brain tumor patients with infratentorial lesions present poor swallowing functions. However, the type of brain tumor as malignancy does not influence swallowing functions. PMID- 24231856 TI - One-step aqueous synthesis of fluorescent copper nanoclusters by direct metal reduction. AB - A one-step aqueous synthesis of highly fluorescent water-soluble copper nanoclusters (CuNCs) is here described, based on direct reduction of the metal precursor with NaBH4 in the presence of bidentate ligands (made of lipoic acid anchoring groups, appended with a poly(ethylene glycol) short chain). A complete optical and structural characterization was carried out: the optical emission was centred at 416 nm, with a luminescence quantum yield in water of 3.6% (the highest one reported so far in water for this kind of nanocluster). The structural characterization reveals a homogeneous size distribution (of 2.5 nm diameter) with spherical shape. The CuNCs obtained offer long-term stability (the luminescence emission remained unaltered after more than two months) under a broad range of chemical conditions (e.g., stored at pH 3-12 or even in a high ionic strength medium such as 1 M NaCl) and high photostability, keeping their fluorescence emission intact after more than 2 h of daylight and UV-light exposition. All those advantageous features warrant synthesized CuNCs being promising fluorescent nanoprobes for further developments including (bio)applications. PMID- 24231858 TI - Superconductivity at the border of electron localization and itinerancy. AB - The superconducting state of iron pnictides and chalcogenides exists at the border of anti-ferromagnetic order. Consequently, these materials could provide clues about the relationship between magnetism and unconventional superconductivity. One explanation, motivated by the so-called bad metal behaviour of these materials proposes that magnetism and superconductivity develop out of quasi-localized magnetic moments that are generated by strong electron-electron correlations. Another suggests that these phenomena are the result of weakly interacting electron states that lie on nested Fermi surfaces. Here we address the issue by comparing the newly discovered alkaline iron selenide superconductors, which exhibit no Fermi-surface nesting, to their iron pnictide counterparts. We show that the strong-coupling approach leads to similar pairing amplitudes in these materials, despite their different Fermi surfaces. We also find that the pairing amplitudes are largest at the boundary between electronic localization and itinerancy, suggesting that new superconductors might be found in materials with similar characteristics. PMID- 24231857 TI - De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. AB - BACKGROUND: In severe sepsis, guidelines recommend de-escalating the empirical antimicrobial treatment as soon as the microbiological results are available. We aimed to determine the rate of de-escalation of the empirical antimicrobial treatment in neutropenic patients with severe sepsis. The characteristics of antimicrobial treatment associated with de-escalation and its impact on short- and long-term survival were also determined. METHODS: In the intensive care unit (ICU) of a cancer referral center, we prospectively collected observational data related to the antimicrobial management in neutropenic patients who developed severe sepsis and were admitted to ICU for at least 48 h. De-escalation of antimicrobial therapy consisted either of deleting one of the empirical antibiotics of a combined treatment, or, whenever possible, to use a betalactam antibiotic with a narrower spectrum of activity. Multivariate logistic regression was conducted to determine the factors associated with de-escalation, while a Cox proportional hazards model with a time-dependent covariate was fitted to assess the effect of de-escalation on 30-day survival. Finally 1-year survival after ICU discharge was compared across de-escalation groups. RESULTS: Cumulative incidence of de-escalation of the empirical antimicrobial treatment among the 101 patients of the cohort was 44%, [95% confidence interval (CI) 38-53%], including 30 (68%) patients with ongoing neutropenia. A microbiological documentation was available in 63 (63%) patients. Factors associated with de-escalation were the adequation of the empirical antimicrobial treatment in ICU [OR = 10.8 (95% CI 1.20-96)] for adequate documented treatment versus appropriate empirical treatment, the compliance with guidelines regarding the empirical choice of the anti-pseudomonal betalactam [OR = 10.8 (95% CI 1.3-89.5)]. De-escalation did not significantly modify the hazard of death within the first 30 days [HR = 0.51 (95% CI 0.20 1.33)], nor within 1 year after ICU discharge [HR = 1.06 (95% CI 0.54-2.08)]. CONCLUSION: Our data suggest that, in ICU, de-escalation of the empirical antimicrobial treatment is frequently applied in neutropenic cancer patients with severe sepsis. No evidence of any prognostic impact of this de-escalation was found. PMID- 24231859 TI - An integrative approach to apprehend desistance. AB - The process underlying desistance is still a strong subject of debate. This article seeks to introduce several core concepts of Archer's morphogenic approach to study how people desist from crime. At first, it discusses the primary existing theories of desistance. Then, this article demonstrates the usefulness of this approach by presenting empirical evidence drawn from semistructured interviews collected with 29 men who desisted from crime in an eastern province of Canada. The study demonstrates how this alternative approach allows for the consolidation of existing knowledge on desistance. Then implication of these findings for both theory and practice are discussed. PMID- 24231860 TI - An outcome evaluation of a prison-based life-skills program: the power of people. AB - The Power of People (PoP) is a personal leadership development course that was originally developed in a non-correctional setting and now serves as a prison based life skills course. This study examined PoP's effect on four different types of recidivism: rearrest, reconviction, reincarceration, and technical violation revocation. The results of the analyses revealed that PoP does not have a significant effect on any of the four measures of recidivism. Following established principles of effective correctional treatment, we make several recommendations that could improve PoP's effectiveness on recidivism outcomes. Overall, this study provides guidance on how to make programs not originally designed for correctional systems into effective recidivism-reducing tools. PMID- 24231861 TI - Easily available nickel complexes as catalysts for the intermolecular hydroamination of alkenes and alkynes. AB - A series of nickel complexes of the type [(P-P)NiX2] ((P-P) = bisphospines or bisphosphites, X = chloride, triflate) were used as catalysts for the hydroamination of both activated and unactivated alkenes and alkynes with pyrrolidine. In general, the use of activated unsaturations, such as acrylonitrile, required mild reaction conditions (e.g. 100 degrees C and 4 h) in comparison with other non-activated alkenes. Particularly with a series of alkynes, the use of nickel(II) centers diminished or even inhibited the formation of otherwise undesired homocoupling and/or transfer hydrogenation by-products, such as the ones obtained in the presence of zerovalent nickel. When using less activated substrates, better selectivity was obtained, although harsher reaction conditions were needed. From a general perspective, the results of this report strongly support the potential use of nickel as a good candidate for further application in the hydroamination of organic unsaturations by means of screening of several pi acceptor ligands. PMID- 24231862 TI - A morphological approach to curvature-based evolution of curves and surfaces. AB - We introduce new results connecting differential and morphological operators that provide a formal and theoretically grounded approach for stable and fast contour evolution. Contour evolution algorithms have been extensively used for boundary detection and tracking in computer vision. The standard solution based on partial differential equations and level-sets requires the use of numerical methods of integration that are costly computationally and may have stability issues. We present a morphological approach to contour evolution based on a new curvature morphological operator valid for surfaces of any dimension. We approximate the numerical solution of the curve evolution PDE by the successive application of a set of morphological operators defined on a binary level-set and with equivalent infinitesimal behavior. These operators are very fast, do not suffer numerical stability issues, and do not degrade the level set function, so there is no need to reinitialize it. Moreover, their implementation is much easier since they do not require the use of sophisticated numerical algorithms. We validate the approach providing a morphological implementation of the geodesic active contours, the active contours without borders, and turbopixels. In the experiments conducted, the morphological implementations converge to solutions equivalent to those achieved by traditional numerical solutions, but with significant gains in simplicity, speed, and stability. PMID- 24231863 TI - Anomaly detection and localization in crowded scenes. AB - The detection and localization of anomalous behaviors in crowded scenes is considered, and a joint detector of temporal and spatial anomalies is proposed. The proposed detector is based on a video representation that accounts for both appearance and dynamics, using a set of mixture of dynamic textures models. These models are used to implement 1) a center-surround discriminant saliency detector that produces spatial saliency scores, and 2) a model of normal behavior that is learned from training data and produces temporal saliency scores. Spatial and temporal anomaly maps are then defined at multiple spatial scales, by considering the scores of these operators at progressively larger regions of support. The multiscale scores act as potentials of a conditional random field that guarantees global consistency of the anomaly judgments. A data set of densely crowded pedestrian walkways is introduced and used to evaluate the proposed anomaly detector. Experiments on this and other data sets show that the latter achieves state-of-the-art anomaly detection results. PMID- 24231864 TI - Asymmetric distances for binary embeddings. AB - In large-scale query-by-example retrieval, embedding image signatures in a binary space offers two benefits: data compression and search efficiency. While most embedding algorithms binarize both query and database signatures, it has been noted that this is not strictly a requirement. Indeed, asymmetric schemes that binarize the database signatures but not the query still enjoy the same two benefits but may provide superior accuracy. In this work, we propose two general asymmetric distances that are applicable to a wide variety of embedding techniques including locality sensitive hashing (LSH), locality sensitive binary codes (LSBC), spectral hashing (SH), PCA embedding (PCAE), PCAE with random rotations (PCAE-RR), and PCAE with iterative quantization (PCAE-ITQ). We experiment on four public benchmarks containing up to 1M images and show that the proposed asymmetric distances consistently lead to large improvements over the symmetric Hamming distance for all binary embedding techniques. PMID- 24231865 TI - Consistent latent position estimation and vertex classification for random dot product graphs. AB - In this work, we show that using the eigen-decomposition of the adjacency matrix, we can consistently estimate latent positions for random dot product graphs provided the latent positions are i.i.d. from some distribution. If class labels are observed for a number of vertices tending to infinity, then we show that the remaining vertices can be classified with error converging to Bayes optimal using the $(k)$-nearest-neighbors classification rule. We evaluate the proposed methods on simulated data and a graph derived from Wikipedia. PMID- 24231866 TI - Continuous energy minimization for multitarget tracking. AB - Many recent advances in multiple target tracking aim at finding a (nearly) optimal set of trajectories within a temporal window. To handle the large space of possible trajectory hypotheses, it is typically reduced to a finite set by some form of data-driven or regular discretization. In this work, we propose an alternative formulation of multitarget tracking as minimization of a continuous energy. Contrary to recent approaches, we focus on designing an energy that corresponds to a more complete representation of the problem, rather than one that is amenable to global optimization. Besides the image evidence, the energy function takes into account physical constraints, such as target dynamics, mutual exclusion, and track persistence. In addition, partial image evidence is handled with explicit occlusion reasoning, and different targets are disambiguated with an appearance model. To nevertheless find strong local minima of the proposed nonconvex energy, we construct a suitable optimization scheme that alternates between continuous conjugate gradient descent and discrete transdimensional jump moves. These moves, which are executed such that they always reduce the energy, allow the search to escape weak minima and explore a much larger portion of the search space of varying dimensionality. We demonstrate the validity of our approach with an extensive quantitative evaluation on several public data sets. PMID- 24231867 TI - Cross-sensor iris recognition through kernel learning. AB - Due to the increasing popularity of iris biometrics, new sensors are being developed for acquiring iris images and existing ones are being continuously upgraded. Re-enrolling users every time a new sensor is deployed is expensive and time-consuming, especially in applications with a large number of enrolled users. However, recent studies show that cross-sensor matching, where the test samples are verified using data enrolled with a different sensor, often lead to reduced performance. In this paper, we propose a machine learning technique to mitigate the cross-sensor performance degradation by adapting the iris samples from one sensor to another. We first present a novel optimization framework for learning transformations on iris biometrics. We then utilize this framework for sensor adaptation, by reducing the distance between samples of the same class, and increasing it between samples of different classes, irrespective of the sensors acquiring them. Extensive evaluations on iris data from multiple sensors demonstrate that the proposed method leads to improvement in cross-sensor recognition accuracy. Furthermore, since the proposed technique requires minimal changes to the iris recognition pipeline, it can easily be incorporated into existing iris recognition systems. PMID- 24231868 TI - Discriminative illumination: per-pixel classification of raw materials based on optimal projections of spectral BRDF. AB - Classifying raw, unpainted materials--metal, plastic, ceramic, fabric, and so on- is an important yet challenging task for computer vision. Previous works measure subsets of surface spectral reflectance as features for classification. However, acquiring the full spectral reflectance is time consuming and error-prone. In this paper, we propose to use coded illumination to directly measure discriminative features for material classification. Optimal illumination patterns--which we call "discriminative illumination"--are learned from training samples, after projecting to which the spectral reflectance of different materials are maximally separated. This projection is automatically realized by the integration of incident light for surface reflection. While a single discriminative illumination is capable of linear, two-class classification, we show that multiple discriminative illuminations can be used for nonlinear and multiclass classification. We also show theoretically that the proposed method has higher signal-to-noise ratio than previous methods due to light multiplexing. Finally, we construct an LED-based multispectral dome and use the discriminative illumination method for classifying a variety of raw materials, including metal (aluminum, alloy, steel, stainless steel, brass, and copper), plastic, ceramic, fabric, and wood. Experimental results demonstrate its effectiveness. PMID- 24231869 TI - Entropy-rate clustering: cluster analysis via maximizing a submodular function subject to a matroid constraint. AB - We propose a new objective function for clustering. This objective function consists of two components: the entropy rate of a random walk on a graph and a balancing term. The entropy rate favors formation of compact and homogeneous clusters, while the balancing function encourages clusters with similar sizes and penalizes larger clusters that aggressively group samples. We present a novel graph construction for the graph associated with the data and show that this construction induces a matroid--a combinatorial structure that generalizes the concept of linear independence in vector spaces. The clustering result is given by the graph topology that maximizes the objective function under the matroid constraint. By exploiting the submodular and monotonic properties of the objective function, we develop an efficient greedy algorithm. Furthermore, we prove an approximation bound of (1/2) for the optimality of the greedy solution. We validate the proposed algorithm on various benchmarks and show its competitive performances with respect to popular clustering algorithms. We further apply it for the task of superpixel segmentation. Experiments on the Berkeley segmentation data set reveal its superior performances over the state-of-the-art superpixel segmentation algorithms in all the standard evaluation metrics. PMID- 24231871 TI - Likelihood-ratio-based verification in high-dimensional spaces. AB - The increase of the dimensionality of data sets often leads to problems during estimation, which are denoted as the curse of dimensionality. One of the problems of second-order statistics (SOS) estimation in high-dimensional data is that the resulting covariance matrices are not full rank, so their inversion, for example, needed in verification systems based on the likelihood ratio, is an ill-posed problem, known as the singularity problem. A classical solution to this problem is the projection of the data onto a lower dimensional subspace using principle component analysis (PCA) and it is assumed that any further estimation on this dimension-reduced data is free from the effects of the high dimensionality. Using theory on SOS estimation in high-dimensional spaces, we show that the solution with PCA is far from optimal in verification systems if the high dimensionality is the sole source of error. For moderate dimensionality, it is already outperformed by solutions based on euclidean distances and it breaks down completely if the dimensionality becomes very high. We propose a new method, the fixed-point eigenwise correction, which does not have these disadvantages and performs close to optimal. PMID- 24231870 TI - Joint sparse representation for robust multimodal biometrics recognition. AB - Traditional biometric recognition systems rely on a single biometric signature for authentication. While the advantage of using multiple sources of information for establishing the identity has been widely recognized, computational models for multimodal biometrics recognition have only recently received attention. We propose a multimodal sparse representation method, which represents the test data by a sparse linear combination of training data, while constraining the observations from different modalities of the test subject to share their sparse representations. Thus, we simultaneously take into account correlations as well as coupling information among biometric modalities. A multimodal quality measure is also proposed to weigh each modality as it gets fused. Furthermore, we also kernelize the algorithm to handle nonlinearity in data. The optimization problem is solved using an efficient alternative direction method. Various experiments show that the proposed method compares favorably with competing fusion-based methods. PMID- 24231872 TI - Temporal analysis of motif mixtures using Dirichlet processes. AB - In this paper, we present a new model for unsupervised discovery of recurrent temporal patterns (or motifs) in time series (or documents). The model is designed to handle the difficult case of multivariate time series obtained from a mixture of activities, that is, our observations are caused by the superposition of multiple phenomena occurring concurrently and with no synchronization. The model uses nonparametric Bayesian methods to describe both the motifs and their occurrences in documents. We derive an inference scheme to automatically and simultaneously recover the recurrent motifs (both their characteristics and number) and their occurrence instants in each document. The model is widely applicable and is illustrated on datasets coming from multiple modalities, mainly videos from static cameras and audio localization data. The rich semantic interpretation that the model offers can be leveraged in tasks such as event counting or for scene analysis. The approach is also used as a mean of doing soft camera calibration in a camera network. A thorough study of the model parameters is provided and a cross-platform implementation of the inference algorithm will be made publicly available. PMID- 24231873 TI - What is optimized in convex relaxations for multilabel problems: connecting discrete and continuously inspired MAP inference. AB - In this work, we present a unified view on Markov random fields (MRFs) and recently proposed continuous tight convex relaxations for multilabel assignment in the image plane. These relaxations are far less biased toward the grid geometry than Markov random fields on grids. It turns out that the continuous methods are nonlinear extensions of the well-established local polytope MRF relaxation. In view of this result, a better understanding of these tight convex relaxations in the discrete setting is obtained. Further, a wider range of optimization methods is now applicable to find a minimizer of the tight formulation. We propose two methods to improve the efficiency of minimization. One uses a weaker, but more efficient continuously inspired approach as initialization and gradually refines the energy where it is necessary. The other one reformulates the dual energy enabling smooth approximations to be used for efficient optimization. We demonstrate the utility of our proposed minimization schemes in numerical experiments. Finally, we generalize the underlying energy formulation from isotropic metric smoothness costs to arbitrary nonmetric and orientation dependent smoothness terms. PMID- 24231874 TI - Learning spectral descriptors for deformable shape correspondence. AB - Informative and discriminative feature descriptors play a fundamental role in deformable shape analysis. For example, they have been successfully employed in correspondence, registration, and retrieval tasks. In recent years, significant attention has been devoted to descriptors obtained from the spectral decomposition of the Laplace-Beltrami operator associated with the shape. Notable examples in this family are the heat kernel signature (HKS) and the recently introduced wave kernel signature (WKS). The Laplacian-based descriptors achieve state-of-the-art performance in numerous shape analysis tasks; they are computationally efficient, isometry-invariant by construction, and can gracefully cope with a variety of transformations. In this paper, we formulate a generic family of parametric spectral descriptors. We argue that to be optimized for a specific task, the descriptor should take into account the statistics of the corpus of shapes to which it is applied (the "signal") and those of the class of transformations to which it is made insensitive (the "noise"). While such statistics are hard to model axiomatically, they can be learned from examples. Following the spirit of the Wiener filter in signal processing, we show a learning scheme for the construction of optimized spectral descriptors and relate it to Mahalanobis metric learning. The superiority of the proposed approach in generating correspondences is demonstrated on synthetic and scanned human figures. We also show that the learned descriptors are robust enough to be learned on synthetic data and transferred successfully to scanned shapes. PMID- 24231875 TI - A compact representation of visual speech data using latent variables. AB - The problem of visual speech recognition involves the decoding of the video dynamics of a talking mouth in a high-dimensional visual space. In this paper, we propose a generative latent variable model to provide a compact representation of visual speech data. The model uses latent variables to separately represent the interspeaker variations of visual appearances and those caused by uttering within images, and incorporates the structural information of the visual data through placing priors of the latent variables along a curve embedded within a path graph. PMID- 24231876 TI - Local difference binary for ultrafast and distinctive feature description. AB - The efficiency and quality of a feature descriptor are critical to the user experience of many computer vision applications. However, the existing descriptors are either too computationally expensive to achieve real-time performance, or not sufficiently distinctive to identify correct matches from a large database with various transformations. In this paper, we propose a highly efficient and distinctive binary descriptor, called local difference binary (LDB). LDB directly computes a binary string for an image patch using simple intensity and gradient difference tests on pairwise grid cells within the patch. A multiple-gridding strategy and a salient bit-selection method are applied to capture the distinct patterns of the patch at different spatial granularities. Experimental results demonstrate that compared to the existing state-of-the-art binary descriptors, primarily designed for speed, LDB has similar construction efficiency, while achieving a greater accuracy and faster speed for mobile object recognition and tracking tasks. PMID- 24231877 TI - Robust and efficient saliency modeling from image co-occurrence histograms. AB - This paper presents a visual saliency modeling technique that is efficient and tolerant to the image scale variation. Different from existing approaches that rely on a large number of filters or complicated learning processes, the proposed technique computes saliency from image histograms. Several two-dimensional image co-occurrence histograms are used, which encode not only "how many" (occurrence) but also "where and how" (co-occurrence) image pixels are composed into a visual image, hence capturing the "unusualness" of an object or image region that is often perceived by either global "uncommonness" (i.e., low occurrence frequency) or local "discontinuity" with respect to the surrounding (i.e., low co-occurrence frequency). The proposed technique has a number of advantageous characteristics. It is fast and very easy to implement. At the same time, it involves minimal parameter tuning, requires no training, and is robust to image scale variation. Experiments on the AIM dataset show that a superior shuffled AUC (sAUC) of 0.7221 is obtained, which is higher than the state-of-the-art sAUC of 0.7187. PMID- 24231878 TI - Indications for valve-pressure adjustments of gravitational assisted valves in patients with idiopathic normal pressure hydrocephalus. AB - BACKGROUND: Modern ventriculoperitoneal shunts (VPS) are programmable, which enables clinicians to adjust valve-pressure according to their patients' individual needs. The aim of this retrospective analysis is to evaluate indications for valve-pressure adjustments in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients operated between 2004 and 2011 diagnosed with iNPH were included. Kiefer-Scale was used to classify each patient. Follow up exams were conducted 3, 6, and 12 months after shunt implantation and yearly thereafter. Initial valve-pressure was 100 or 70 mmH2O. Planned reductions of the valve-pressure to 70 and 50 mmH2O, respectively, were carried out and reactive adjustment of the valve-pressure to avoid over- and under-drainage were indicated. RESULTS: A total of 52 patients were provided with a Medos-Hakim valve(Codman(r)) with a Miethke shunt-assistant(Aesculap(r)) and 111 patients with a Miethke-proGAV(Aesculap(r)). 180 reductions of the valve-pressure took place (65% reactive, 35% planned). Most patients (89%) needed one or two adjustments of their valve-pressures for optimal results. In 41%, an improvement of the symptoms was observed. Gait disorder was improved most often after valve pressure adjustments (32%). 18 times an elevation of valve-pressure was necessary because of headaches, vertigo, or the development of subdural hygroma. Optimal valve-pressure for most patients was around 50 mmH2O (36%). CONCLUSION: The goal of shunt therapy in iNPH should usually be valve-pressure settings between 30 and 70 mmH2O. Reactive adjustments of the valve-pressure are useful for therapy of over- and underdrainage symptoms. Planned reductions of the valve opening pressure are effective even if postoperative results are already satisfactory. PMID- 24231881 TI - (14)C-labeling of the compounds excreted by phytoplankton for employment as a realistic tracer in secondary productivity measurements. AB - Preparations of the dissolved organic compounds released by photosynthesizing marine phytoplankton have been obtained with(14)carbon activities as high as 1.5 * 10(5) dpm/ml. The radioisotope content of the preparations resides wholly in dissolved organic compounds of low molecular weight (MW<3500), which are uncontaminated by residual(14)C-labeled inorganic carbon. The labeled compunds arise through photosynthetic fixation and do not appear to be products of cell lysis during the incubation or to originate from cell damage during the filtration step employed. PMID- 24231880 TI - Tubular Enhanced Geodesic Active Contours for Continuum Robot Detection using 3D Ultrasound. AB - Three dimensional ultrasound is a promising imaging modality for minimally invasive robotic surgery. As the robots are typically metallic, they interact strongly with the sound waves in ways that are not modeled by the ultrasound system's signal processing algorithms. Consequently, they produce substantial imaging artifacts that can make image guidance difficult, even for experienced surgeons. This paper introduces a new approach for detecting curved continuum robots in 3D ultrasound images. The proposed approach combines geodesic active contours with a speed function that is based on enhancing the "tubularity" of the continuum robot. In particular, it takes advantage of the known robot diameter along its length. It also takes advantage of the fact that the robot surface facing the ultrasound probe provides the most accurate image. This method, termed Tubular Enhanced Geodesic Active Contours (TEGAC), is demonstrated through ex vivo intracardiac experiments to offer superior performance compared to conventional active contours. PMID- 24231879 TI - Long-term drug treatment for obesity: a systematic and clinical review. AB - IMPORTANCE: Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone. OBJECTIVE: To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice. EVIDENCE REVIEW: A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed. FINDINGS: Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate-extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate-extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy. CONCLUSIONS AND RELEVANCE: Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit. PMID- 24231882 TI - Thiosulfate stimulation of microbial dark assimilation of carbon dioxide in shallow marine waters. AB - The effect of thiosulfate on dark assimilation of carbon dioxide in shallow marine environments was investigated in order to explain the recent discovery of bacterial thiosulfate oxidation in aerobic, open ocean seawater. The results demonstrate that the potential exists for microbial thiosulfate oxidation to increase both dark assimilation of carbon dioxide and the utilization of organic compounds in the sea. Thiosulfate-stimulated microbial activity may be caused not only by chemoautotrophic sulfur bacteria, but also by heterotrophic species which oxidize thiosulfate to tetrathionate. Measurements of dark assimilation of carbon dioxide made at different incubation times indicate that great care must be taken both in experimental procedure and in interpretation of results obtained with the dark assimilation technique. PMID- 24231883 TI - Ciliates as a food source for marine planktonic copepods. AB - Copepods of the genusEurytemora, isolated from the Patuxent River, a tributary of Chesapeake Bay, were fed suspensions of the ciliateUronema isolated from the Rhode River, a subestuary of Chesapeake Bay. Grazing by copepods was determined by the decrease in numbers of ciliates, which were monitored by both direct counting and particle size analysis. Results from both methods of analysis showed significant reduction in the numbers ofUronema in the suspension whenEurytemora was present. Survival of copepods with ciliates added as food source was significantly longer than without ciliates. Analysis of field samples collected in the fall showed that ciliates comprised approximately 20% of the total plankton biomass at selected sampling sites. The results of the laboratory and field studies indicate that copepods can feed on ciliates and suggest that, in nature, ciliates may comprise an important source of food for copepods. PMID- 24231884 TI - Microbial populations on Douglas fir needle surfaces. AB - The surface microflora on Douglas fir (Pseudotsuga menziesii (Mirb.) Franco.) foliage from old-growth trees in western Oregon has been examined by epifluorescence and scanning electron microscopy. Colonies of microorganisms on both upper and lower surfaces of 1-, 3-, 5-, and 8-year-old needles from three heights in the canopy of a single tree have been counted in belt transects, and the relative abundance of various categories of microorganisms has been computed. Aggregations of microbial cells are prevalent in the midrib depression along the upper surface and in stomatal cavities and gutters between rows of epidermal cells on the lower surface. Darkly pigmented hyphae and clumps of cells occur, in general, more frequently on the upper needle surface, a habitat more subject to desiccation and UV exposure.Protococcus colonies become abundant on both upper and lower surfaces of older needles. Microbial cover was found to be significantly higher on the bottom of the needle than on the top. The factors involved in this effect are considered and discussed. PMID- 24231885 TI - A computer study of the evolution of aerobic heterotrophic bacterial populations in sewage and river waters. AB - The biodegradation of six surface active agents tested. The biochemical characteristics of the aerobic heterotrophic bacteria present in Montpellier waste waters and in Rhone water, before and after degradation, were studied by a standardized microbiological method. Four hundred strains isolated from these populations were compared to 29 reference strains by computer analysis. The reference strains were first grouped in classes (single linkage). Then the strains were compared first to these classes, and then to each reference strain. Whereas the bacterial populations were widely distributed before biodegradation, after degradation they were restricted to a few prevailing genera:Pseudomonas, Alcaligenes, andKlebsiella. PMID- 24231886 TI - Estimation of downwind viable airborne microbes from a wet cooling tower Including settling. AB - In recent years, reuse of municipal waste water as the coolant in drift-producing cooling towers at electrical generating plants has become increasingly common. A hueristic model is presented that can be used to estimate the concentrations of viable airborne microbes in the drift from a wet cooling tower given the concentration of microbes in the cooling tower. The purpose of this presentation is to allow the nonmeteorologist to understand the factors affecting airborne concentration and to make crude estimates of ground-level concentrations of airborne microorganisms. Concentrations are calculated using a standard meterological method, the Gaussian dispersion model, in which terms have been included for droplet settling and microbial death rate. PMID- 24231887 TI - Microbial populations associated with the surface of the brown algaAscophyllum nodosum. AB - The microorganisms on the surface of the brown algaAscophyllum nodosum, collected from an intertidal area in Nahant, Massachusetts, were examined using scanning electron microscopy. Differences in the microbial populations on the holdfast, internodal regions of the stipe, and the apical tips were apparent. The populations ranged from a lawn of end-attached bacteria above the holdfast to microcolonies of yeast cells near the apical tips. The greatest diversity of microorganisms was noted in the internodal region representing the fourth year of growth where a dense lawn of end-attached bacteria was overlaid by filamentous bacteria, pennate diatoms, and filamentous blue-green algae. A simple procedure was developed to estimate the number of bacteria on the surface of the seaweed using the scanning electron microscope. The observed distribution of epiphytes may be explained in terms of the age of the algal surface, differences in light intensity, and the differential secretion of tannin by various parts ofAscophyllum. PMID- 24231888 TI - Cultural differences in clinical leadership: a qualitative study comparing the attitudes of general dental practitioners from Greater Manchester and Tokyo. AB - BACKGROUND AND AIMS: Leadership has been argued to be a key component in the transformation of services in the United Kingdom and in Japan. In the UK, local professional networks have developed to provide clinician led care in dentistry; working to develop local plans to deliver improvements in the quality of care for patients. In Japan, the remuneration model for dental care has been revised with the aim to improve the service and tackle the current challenges of population health there. The aim of this study was to use semi-structured interviews and thematic analysis to explore general dental practitioners' (GDPs) understanding of the term 'leadership' and determine whether its meaning is culturally bound. METHODS: Twelve participants were sampled purposively by the research team; identifying GDPs involved in leadership roles from across Greater Manchester and Tokyo. A set of open-ended questions was developed for semi-structured interviews a priori and the interviews continued until saturation. Interviews were recorded, transcribed verbatim and codes were developed into a coding frame for thematic analysis. Representative quotations are provided in the results. RESULTS: Fourteen codes were identified according to the aims of the study and organised into five overarching themes. 'Leadership as the relationship' was more pronounced among Japanese GDPs, while 'leadership as the individual' was common in GDPs from Greater Manchester. Differences were also found in respect of education and training in leadership. Training was also considered to be important by the GDPs from Japan, while UK GDPs felt leaders were more likely to be influenced by innate qualities. The interdependence of leadership and entrepreneurship was raised by both sets of GDPs. CONCLUSION: The concept of leadership was considered to be important by GDPs from both Greater Manchester and Tokyo; leadership was seen as providing strategy and direction for a clinical team. However, cultural influences were evident in how this was conceptualised. PMID- 24231889 TI - Knowledge of removable partial denture wearers on denture hygiene. AB - BACKGROUND: Regular good denture hygiene by individuals with removable partial dentures (RPDs) is an important component of oral health and in the prevention of further dental problems. These individuals should be provided with advice on the importance of denture care and be aware of this information. AIM: To establish deficiencies in patient knowledge surrounding denture hygiene by RPD wearers. METHODOLOGY: The study was undertaken as an audit. Data was collected from April 2012 to October 2012 via a questionnaire completed by 196 RPD wearers attending as patients at the University Dental Hospital Wales and the dental units at St David's Hospital and Cynon Valley Hospital. The audit criterion was patients with RPDs should have knowledge of denture hygiene, with the standard set at 100%. RESULTS: While 91.8% of participants stated they were provided with instructions on denture hygiene when provided with their current prosthesis, 60.2% were shown to have less than an appropriate level of denture cleanliness, with 9.2% reporting that they slept wearing their prosthesis. CONCLUSION: The audit criterion and standard set were not achieved. A lack of knowledge surrounding denture hygiene was demonstrated among participants. As a part of the audit process the health education of RPD wearers' hygiene needs to be improved and awareness levels of the whole dental team needs to be raised. All partial dentures should receive information and regular reinforcement of key dental hygiene messages. PMID- 24231891 TI - Adapting heart failure guidelines for nursing care in home health settings: challenges and solutions. AB - BACKGROUND: Nurses provide most of home health services for patients with heart failure, and yet there are no evidence-based practice guidelines developed for home health nurses. PURPOSE: The purpose of this article was to review the challenges and solutions for adapting generally available HF clinical practice guidelines to home health nursing. METHODS: Appropriate HF guidelines were identified and home health nursing-relevant guidelines were extracted by the research team. In addition, a team of nursing academic and practice experts evaluated the extracted guidelines and reached consensus through Delphi rounds. RESULTS: We identified 172 recommendations relevant to home health nursing from the American Heart Association and Heart Failure Society of America guidelines. The recommendations were divided into 5 groups (generic, minority populations, normal ejection fraction, reduced ejection fraction, and comorbidities) and further subgroups. Experts agreed that 87% of the recommendations selected by the research team were relevant to home health nursing and rejected 6% of the selected recommendations. Experts' opinions were split on 7% of guideline recommendations. Experts mostly disagreed on recommendations related to HF medication and laboratory prescription as well as HF patient assessment. These disagreements were due to lack of patient information available to home health nurses as well as unclear understanding of scope of practice regulations for home health nursing. After 2 Delphi rounds over 8 months, we achieved 100% agreement on the recommendations. The finalized guideline included 153 recommendations. CONCLUSIONS: Guideline adaptation projects should include a broad scope of nursing practice recommendations from which home health agencies can customize relevant recommendations in accordance with available information and state and agency regulations. PMID- 24231890 TI - Using brief motivational interviewing to address the complex needs of a challenging patient with heart failure. AB - BACKGROUND: Hospitals and healthcare providers are looking for methods to reduce hospitalization rates and improve patient outcomes for patients with heart failure (HF). Using behavioral approaches to increase patients' confidence in their abilities to perform self-care is 1 such approach. Motivational interviewing is an empirically validated modality that has shown promise in improving motivation to change and confidence in the ability to do so. OBJECTIVE: This case represents a number of themes common in the management of care for a HF patient and explores a 4-session brief motivational interviewing approach to address these themes. The manner in which patient frustration is linked to hospitalization is discussed along with possible ways to address problems in self care behaviors. CONCLUSIONS: With the use of this brief motivational interviewing approach, the patient reported an increase in her motivation and ability to change and developed a postdischarge plan for incorporating self-care behaviors in her daily routine. CLINICAL IMPLICATIONS: Motivational interviewing may be an effective method of increasing the self-care behaviors of patients with HF. PMID- 24231892 TI - A phenomenological study of day-to-day experiences of living with heart failure: do cultural differences matter? AB - OBJECTIVE: Although there is a significant body of literature addressing heart failure (HF) epidemiology, physiology, and treatment, little is known about the experiences of Thai patients living with this chronic condition. The primary goal of this study was to gain a better understanding of how Thai patients with HF live with chronic and debilitating illness. METHODS: A phenomenological approach was chosen to investigate the experience of living with HF. Fifteen Thai men and women with HF in New York Heart Association classes I to III, aged between 47 and 75 years, were interviewed with open-ended questions. Data were analyzed using qualitative inductive content analysis. RESULTS: Three themes emerged from the data analysis: identifying losses or changes in their lives, accepting the losses, and regaining some control. Unlike their western counterparts, the Thai patients with HF incorporated their karma, a Buddhist belief system, as a tool to rationalize the occurrence of their HF experience. The participants of this study used kreng jai as a cultural desire not to disrupt the happiness of others, even at the expense of efficiency, or to burden others, which might affect their own quality of life. CONCLUSIONS: The Thai patients with HF faced many limitations. The Thai patients with HF use religion and traditional culture to overcome their life situations. To support Thai patients with HF, healthcare providers must have an understanding of cultural differences. PMID- 24231893 TI - Left ventricular noncompaction: a cardiomyopathy with distinct characteristics and risks. AB - BACKGROUND: Left ventricular noncompaction (LVNC) cardiomyopathy is a heterogeneous condition that is gaining recognition as a distinct clinical entity. It is characterized by numerous, excessively prominent ventricular trabeculations with deep trabecular recesses and the formation of 2 distinct layers of myocardium. It is often unrecognized clinically for decades and poses distinct life-threatening complications. Accurate diagnosis is key to minimizing risks associated with LVNC. PURPOSE: This article will introduce clinicians to the defining criteria and diagnostic process for recognition of LVNC. Left ventricular noncompaction is an important clinical entity not easily recognized at first glance but has important clinical ramifications for treatment requiring an accurate diagnosis. CONCLUSIONS: Left ventricular noncompaction is present at birth but can remain clinically silent for decades. It is found both in isolation and as a part of other congenital cardiac, extracardiac, neuromuscular, and genetic syndromes. Left ventricular noncompaction is associated with the major complications of heart failure, tachyarrhythmias, and systemic thromboembolism. CLINICAL IMPLICATIONS: Transthoracic echocardiography will likely remain the initial screening modality, but modality limitations, questionable findings, and clinical presentations suspicious for noncompaction should be followed up promptly with cardiac magnetic resonance imaging for definitive diagnosis and treatment. PMID- 24231894 TI - Lomitapide and mipomersen: novel lipid-lowering agents for the management of familial hypercholesterolemia. AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused primarily by mutations in the low-density lipoprotein receptor gene. Familial hypercholesterolemia is characterized by exceedingly high levels of low density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Homozygous FH (HoFH) is less prevalent, but more severe, than heterozygous FH. Current treatment options include dietary therapy, lipid lowering agents (eg, statins), and/or LDL-C apheresis. PURPOSE: Despite the available treatment options, patients with FH rarely attain treatment goals. This review will focus on 2 novel agents, lomitapide and mipomersen, with recently approved US Food and Drug Administration (FDA) labeling for use in patients with HoFH. CONCLUSIONS: Lomitapide and mipomersen are 2 agents with novel mechanisms of action and the ability to significantly lower LDL-C, apolipoprotein B, and non high-density lipoprotein cholesterol levels. A black box warning exists for lomitapide and mipomersen regarding the risk for transaminase elevations and hepatic steatosis. Furthermore, these agents are currently restricted for use only in patients with HoFH and have been required by the FDA to participate in a Risk Evaluation and Mitigation Strategy. CLINICAL IMPLICATIONS: These new agents offer additional treatment options for clinicians managing patients with HoFH, but it remains uncertain whether lomitapide and mipomersen will gain FDA approval for use in patients with heterozygous FH or in the general population. Cost and concern for the risk for hepatotoxicity will remain limiting factors to these agents being more widely used. PMID- 24231896 TI - Specimen-specific computational models of ankle sprains produced in a laboratory setting. AB - The use of computational modeling to predict injury mechanisms and severity has recently been investigated, but few models report failure level ligament strains. The hypothesis of the study was that models built off neutral ankle experimental studies would generate the highest ligament strain at failure in the anterior deltoid ligament, comprised of the anterior tibiotalar ligament (ATiTL) and tibionavicular ligament (TiNL). For models built off everted ankle experimental studies the highest strain at failure would be developed in the anterior tibiofibular ligament (ATiFL). An additional objective of the study was to show that in these computational models ligament strain would be lower when modeling a partial versus complete ligament rupture experiment. To simulate a prior cadaver study in which six pairs of cadaver ankles underwent external rotation until gross failure, six specimen-specific models were built based on computed tomography (CT) scans from each specimen. The models were initially positioned with 20 deg dorsiflexion and either everted 20 deg or maintained at neutral to simulate the cadaver experiments. Then each model underwent dynamic external rotation up to the maximum angle at failure in the experiments, at which point the peak strains in the ligaments were calculated. Neutral ankle models predicted the average of highest strain in the ATiTL (29.1 +/- 5.3%), correlating with the medial ankle sprains in the neutral cadaver experiments. Everted ankle models predicted the average of highest strain in the ATiFL (31.2 +/- 4.3%) correlating with the high ankle sprains documented in everted experiments. Strains predicted for ligaments that suffered gross injuries were significantly higher than the strains in ligaments suffering only a partial tear. The correlation between strain and ligament damage demonstrates the potential for modeling to provide important information for the study of injury mechanisms and for aiding in treatment procedure. PMID- 24231895 TI - Predicting coronary heart disease events in women: a longitudinal cohort study. AB - BACKGROUND: More than 240 000 women in the United States die of coronary heart disease annually. Identifying women's symptoms that predict a coronary heart disease event such as myocardial infarction (MI) could decrease mortality. OBJECTIVE: For this longitudinal observational study, we recruited 1097 women, who were either clinician referred or self-referred to a cardiologist and undergoing initial evaluation by a cardiologist, to assess the utility of the prodromal symptoms (PS) section of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) in predicting the occurrence of cardiac events in women. METHODS AND RESULTS: Seventy-seven women experienced events (angioplasty, stent placement, coronary artery bypass, MI, death) during the 2 year follow up. The most common events were stents alone (38.9%) or in combination with angioplasty (18.2%). Ten women had MIs; 4 experienced cardiac death. Cox proportional hazards was used to model time to event. The prodromal score was significantly associated with risk of an event (hazard ratio, 1.10; 95% confidence interval, 1.06-1.13), as was the number of PSs endorsed by each woman per visit. After covariate adjustment, 5 symptoms were significantly associated with increased risk: discomfort in jaws/teeth, unusual fatigue, arm discomfort, shortness of breath, and general chest discomfort (hazard ratio, 3.97; 95% confidence interval, 2.32-6.78). Women reporting 1 or more of these symptoms were 4 times as likely to experience a cardiac event as women with none. CONCLUSIONS: Both the MAPMISS PS scores and number of PS were significantly associated with cardiac events, independent of risk factors, suggesting that there are specific PSs that can be easily assessed using the MAPMISS. This instrument could be an important component of a predictive screen to assist clinicians in deciding the course of management for women. PMID- 24231897 TI - The effect of the variation in ACL constitutive model on joint kinematics and biomechanics under different loads: a finite element study. AB - The biomechanics and function of the anterior cruciate ligament (ACL) have been widely studied using both experimental and simulation methods. It is known that a constitutive model of joint tissue is a critical factor in the numerical simulation. Some different ligament constitutive models have been presented to describe the ACL material behavior. However, the effect of the variation in the ligament constitutive model on joint kinematics and biomechanics has still not been studied. In this paper, a three-dimensional finite element model of an intact tibiofemoral joint was reconstructed. Three ACL constitutive models were compared under different joint loads (such as anterior tibial force, varus tibial torque, and valgus tibial torque) to investigate the effect of the change of the ACL constitutive model. The three constitutive models corresponded to an isotropic hyperelasticity model, a transversely isotropic hyperelasticity model with neo-Hookean ground substance description, and a transversely isotropic hyperelastic model with nonlinear ground substance description. Although the material properties of these constitutive equations were fitted on the same uniaxial tension stress-strain curve, the change of the ACL material constitutive model was found to induce altered joint kinematics and biomechanics. The effect of different ACL constitutive equations on joint kinematics depended on both deformation direction and load type. The variation in the ACL constitutive models would influence the joint kinematic results greatly in both the anterior and internal directions under anterior tibial force as well as some other deformations such as the anterior and medial tibial translations under valgus tibial torque, and the medial tibial translation and internal rotation under varus torque. It was revealed that the transversely isotropic hyperelastic model with nonlinear ground substance description (FE model III) was the best representation of the realistic ACL property by a linear regression between the simulated and the experiment deformation results. But the comparison of the predicted and experiment force of ligaments showed that all the three ACL constitutive models represented similar force results. The stress value and distribution of ACL were also altered by the change in the constitutive equation. In brief, although different ACL constitutive models have been fitted using the same uniaxial tension curve and have the similar longitudinal material property, the ACL constitutive equation should still be carefully chosen to investigate joint kinematics and biomechanics due to the different transverse material behavior. PMID- 24231898 TI - Theoretical analysis of the state of balance in bipedal walking. AB - This paper presents a theoretical analysis based on classic mechanical principles of balance of forces in bipedal walking. Theories on the state of balance have been proposed in the area of humanoid robotics and although the laws of classical mechanics are equivalent to both humans and humanoid robots, the resulting motion obtained with these theories is unnatural when compared to normal human gait. Humanoid robots are commonly controlled using the zero moment point (ZMP) with the condition that the ZMP cannot exit the foot-support area. This condition is derived from a physical model in which the biped must always walk under dynamically balanced conditions, making the centre of pressure (CoP) and the ZMP always coincident. On the contrary, humans follow a different strategy characterized by a 'controlled fall' at the end of the swing phase. In this paper, we present a thorough theoretical analysis of the state of balance and show that the ZMP can exit the support area, and its location is representative of the imbalance state characterized by the separation between the ZMP and the CoP. Since humans exhibit this behavior, we also present proof-of-concept results of a single subject walking on an instrumented treadmill at different speeds (from slow 0.7 m/s to fast 2.0 m/s walking with increments of 0.1 m/s) with the motion recorded using an optical motion tracking system. In order to evaluate the experimental results of this model, the coefficient of determination (R2) is used to correlate the measured ground reaction forces and the resultant of inertial and gravitational forces (anteroposterior R2 = 0.93, mediolateral R2 = 0.89, and vertical R2 = 0.86) indicating that there is a high correlation between the measurements. The results suggest that the subject exhibits a complete dynamically balanced gait during slow speeds while experiencing a controlled fall (end of swing phase) with faster speeds. This is quantified with the root-mean square deviation (RMSD) between the CoP and the ZMP, a relationship that grows exponentially, suggesting that the ZMP exits the support area earlier with faster walking speeds (relative to the stride duration). We conclude that the ZMP is a significant concept that can be exploited for the analysis of bipedal balance, but we also challenge the control strategy adopted in humanoid robotics that forces the ZMP to be contained within the support area causing the robot to follow unnatural patterns. PMID- 24231899 TI - An analytical approach to study the intraoperative fractures of femoral shaft during total hip arthroplasty. AB - An analytical approach which is popular in micromechanical studies has been extended to the solution for the interference fit problem of the femoral stem in cementless total hip arthroplasty (THA). The multiple inhomogeneity problem of THA in transverse plane, including an elliptical stem, a cortical wall, and a cancellous layer interface, was formulated using the equivalent inclusion method (EIM) to obtain the induced interference elastic fields. Results indicated a maximum interference fit of about 210 MUm before bone fracture, predicted based on the Drucker-Prager criterion for a partially reamed section. The cancellous layer had a significant effect on reducing the hoop stresses in the cortical wall; the maximum press fit increased to as high as 480 MUm for a 2 mm thick cancellous. The increase of the thickness and the mechanical quality, i.e., stiffness and strength, of the cortical wall also increased the maximum interference fit before fracture significantly. No considerable effect was found for the implant material on the maximum allowable interference fit. It was concluded that while larger interference fits could be adapted for younger patients, care must be taken when dealing with the elderly and those suffering from osteoporosis. A conservative reaming procedure is beneficial for such patients; however, in order to ensure sufficient primary stability without risking bone fracture, a preoperative analysis might be necessary. PMID- 24231900 TI - Validation of an empirical damage model for aging and in vivo injury of the murine patellar tendon. AB - While useful models have been proposed to predict the mechanical impact of damage in tendon and other soft tissues, the applicability of these models for describing in vivo injury and age-related degeneration has not been investigated. Therefore, the objective of this study was to develop and validate a simple damage model to predict mechanical alterations in mouse patellar tendons after aging, injury, or healing. To characterize baseline properties, uninjured controls at age 150 days were cyclically loaded across three strain levels and five frequencies. For comparison, damage was induced in mature (120 day-old) mice through either injury or aging. Injured mice were sacrificed at three or six weeks after surgery, while aged mice were sacrificed at either 300 or 570 days old. Changes in mechanical properties (relative to baseline) in the three week post-injury group were assessed and used to develop an empirical damage model based on a simple damage parameter related to the equilibrium stress at a prescribed strain (6%). From the derived model, the viscoelastic properties of the 300 day-old, 570 day-old, and six week post-injury groups were accurately predicted. Across testing conditions, nearly all correlations between predicted and measured parameters were statistically significant and coefficients of determination ranged from R2 = 0.25 to 0.97. Results suggest that the proposed damage model could exploit simple in vivo mechanical measurements to predict how an injured or aged tendon will respond to complex physiological loading regimens. PMID- 24231901 TI - Quantifying function in the early embryonic heart. AB - Congenital heart defects arise during the early stages of development, and studies have linked abnormal blood flow and irregular cardiac function to improper cardiac morphogenesis. The embryonic zebrafish offers superb optical access for live imaging of heart development. Here, we build upon previously used techniques to develop a methodology for quantifying cardiac function in the embryonic zebrafish model. Imaging was performed using bright field microscopy at 1500 frames/s at 0.76 MUm/pixel. Heart function was manipulated in a wild-type zebrafish at ~55 h post fertilization (hpf). Blood velocity and luminal diameter were measured at the atrial inlet and atrioventricular junction (AVJ) by analyzing spatiotemporal plots. Control volume analysis was used to estimate the flow rate waveform, retrograde fractions, stroke volume, and cardiac output. The diameter and flow waveforms at the inlet and AVJ are highly repeatable between heart beats. We have developed a methodology for quantifying overall heart function, which can be applied to early stages of zebrafish development. PMID- 24231902 TI - Multibody muscle driven model of an instrumented prosthetic knee during squat and toe rise motions. AB - Detailed knowledge of knee joint kinematics and dynamic loading is essential for improving the design and outcomes of surgical procedures, tissue engineering applications, prosthetics design, and rehabilitation. The need for dynamic computational models that link kinematics, muscle and ligament forces, and joint contacts has long been recognized but such body-level forward dynamic models do not exist in recent literature. A main barrier in using computational models in the clinic is the validation of the in vivo contact, muscle, and ligament loads. The purpose of this study was to develop a full body, muscle driven dynamic model with subject specific leg geometries and validate it during squat and toe-rise motions. The model predicted loads were compared to in vivo measurements acquired with an instrumented knee implant. Data for this study were provided by the "Grand Challenge Competition to Predict In-Vivo Knee Loads" for the 2012 American Society of Mechanical Engineers Summer Bioengineering Conference. Data included implant and bone geometries, ground reaction forces, EMG, and the instrumented knee implant measurements. The subject specific model was developed in the multibody framework. The knee model included three ligament bundles for the lateral collateral ligament (LCL) and the medial collateral ligament (MCL), and one bundle for the posterior cruciate ligament (PCL). The implanted tibia tray was segmented into 326 hexahedral elements and deformable contacts were defined between the elements and the femoral component. The model also included 45 muscles on each leg. Muscle forces were computed for the muscle driven simulation by a feedback controller that used the error between the current muscle length in the forward simulation and the muscle length recorded during a kinematics driven inverse simulation. The predicted tibia forces and torques, ground reaction forces, electromyography (EMG) patterns, and kinematics were compared to the experimentally measured values to validate the model. Comparisons were done graphically and by calculating the mean average deviation (MAD) and root mean squared deviation (RMSD) for all outcomes. The MAD value for the tibia vertical force was 279 N for the squat motion and 325 N for the toe-rise motion, 45 N and 53 N for left and right foot ground reaction forces during the squat and 94 N and 82 N for toe-rise motion. The maximum MAD value for any of the kinematic outcomes was 7.5 deg for knee flexion-extension during the toe-rise motion. PMID- 24231903 TI - Rectus femoris knee muscle moment arms measured in vivo during dynamic motion with real-time magnetic resonance imaging. AB - Moment arms represent a muscle's ability to generate a moment about a joint for a given muscle force. The goal of this study was to develop a method to measure muscle moment arms in vivo over a large range of motion using real-time magnetic resonance (MR) imaging. Rectus femoris muscle-tendon lengths and knee joint angles of healthy subjects (N = 4) were measured during dynamic knee joint flexion and extension in a large-bore magnetic resonance imaging (MRI) scanner. Muscle-tendon moment arms were determined at the knee using the tendon-excursion method by differentiating measured muscle-tendon length with respect to joint angle. Rectus femoris moment arms were averaged across a group of healthy subjects and were found to vary similarly during knee joint flexion (mean: 3.0 (SD 0.5) cm, maximum: 3.5 cm) and extension (mean: 2.8 (SD 0.4) cm, maximum: 3.6 cm). These moment arms compare favorably with previously published dynamic tendon excursion measurements in cadaveric specimens but were relatively smaller than moment arms from center-of-rotation studies. The method presented here provides a new approach to measure muscle-tendon moment arms in vivo and has the potential to be a powerful resource for characterizing musculoskeletal geometry during dynamic joint motion. PMID- 24231904 TI - Accuracy of individual trabecula segmentation based plate and rod finite element models in idealized trabecular bone microstructure. AB - Currently, specimen-specific micro finite element (MUFE) analysis based micro computed tomography (MUCT) images have become a major computational tool for the assessment of the mechanical properties of human trabecular bone. Despite the fine characterization of the three-dimensional (3D) trabecular microstructure based on high-resolution MUCT images, conventional MUFE models with each voxel converted to an element are not efficient in predicting the nonlinear failure behavior of bone due to a prohibitive computational cost. Recently, a highly efficient individual trabecula segmentation (ITS)-based plate and rod (PR) modeling technique has been developed by substituting individual plates and rods with shell and beam elements, respectively. In this technical brief, the accuracy of novel PR MUFE models was examined in idealized microstructure models over a broad range of trabecular thicknesses. The Young's modulus and yield strength predicted by simplified PR models strongly correlated with those of voxel models at various voxel sizes. The conversion from voxel models to PR models resulted in an ~762-fold reduction in the largest model size and significantly accelerated the nonlinear FE analysis. The excellent predictive power of the PR MUFE models, demonstrated in an idealized trabecular microstructure, provided a quantitative mechanical basis for this promising tool for an accurate and efficient assessment of trabecular bone mechanics and fracture risk. PMID- 24231906 TI - The World - Socio-economically and politically: What you need to know. AB - The gravest challenge facing the USA and the nations of the world is the coming economic crisis of the world economies, if present policies are pursued. Few are aware or believe that this event could happen. The spread of centralized government control of the economies, the growth of the welfare state worldwide, the expenditures on entitlements beyond what any nation or even most states can afford, the cost of wars, the rapidly climbing debt of the USA and other countries and their inability to pay for these excessive expenses, the actions of many countries to print "fiat" (false) money to pay for their debts, the raising of taxes to pay for these debts, the rise in immigration to developed countries from the undeveloped world, the associated costs to their societies of this immigration, the promises made by politicians to get elected that cannot be fulfilled, and the desire of the public to have what they want, now, paid for by credit cards (debt), are all contributing to the coming economic crisis. The unfunded promised benefits to the citizens of the USA in Medicare, Medicaid, Social Security, and pensions plus the USA debt amount to about $140 trillion. The total value of all the assets of all the people in the USA is $99 trillion dollars. So, one can see that the people of the USA do not have the resources to pay their expenses. Besides, these entitlements, the rest of the expenses are paid for with borrowed or printed (fiat) money that has little chance of being repaid unless perhaps by subsequent generations or by increases in taxes. Efforts to correct this coming economic crisis by austerity and sacrifice have been rejected by the public and the politicians worldwide. The Governments and the Press have participated in deception of the public about these issues in order to maintain their positions of power, for the truth would destroy them. No solution is in sight except more spending and valueless money printing. This unchecked desire for more of everything without the responsibility to work or pay for these entitlements, has touched many countries and people with a few exceptions. This problem is the result of a worldwide breakdown of ethics and morality in society and a desire of the few for centralized control and power over the people. No country has instituted a solution to these problems that results in reducing expenditures or the growing debts. As many have stated in this paper, this policy cannot be sustained. The result of this scenario will be a worldwide economic crisis. Fundamental to this impending economic crisis is the failure of centrally controlled economies and socialistic programs. Those selected groups, who benefit from having control, are the politicians, bankers, some selected industry leaders, and socialist planners, who will stop at nothing to maintain power and control over the people. Liberty of the people is in jeopardy worldwide. Read the evidence presented and decide if this summary is correct. The troubling question is, "What will happen if the world economy collapses?" Will this crisis be a time for the few to take more control of the people through fear, crisis decisions, misinformation, prevention of the public from protecting themselves with guns, and pervasive spying technology on each citizen or will more democratic governments arise from the failure of centralized control, the welfare state, and the loss of liberty? Such crises have been repeated throughout 4000 years of recorded history. What happened in those past times? Read the quotations of Vladimir Lenin, developer of Marxism-Leninism, the foundation of Communism and judge what you have read from his statements. An alternative to this dismal scenario is little discussed also in the Press. Why not? In the past 150 years, the alternative has happened with a rapid growth in democracy, communications technology, and life expectancy from advances in science and medicine. To unleash this huge human potential, at this time, will require individual freedom to create and innovate with the opportunity for risk and reward in an environment aided by unrestrictive governments even at the community and organizational levels. History records the success of the alternatives in the great leadership and creativity of humankind. The USA and the world are at the critical choice for their futures. We are experiencing the results of centrally controlling governments worldwide that are not working. Is it time for an alternative option? Read the evidence in this paper and decide for yourself. Reading this paper will take you time, but you will not read all of this information elsewhere. It is key to your future. Decide for yourself what you should do after reading it. The URLs of many of the references are included so that you can read further about the many subjects presented yourself. PMID- 24231907 TI - Prophylactic level II neck dissection guided by frozen section for clinically node-negative papillary thyroid carcinoma: is it useful? AB - BACKGROUND: Prophylactic lateral neck dissection (PLND) is generally not performed for papillary thyroid carcinoma(PTC). When performed, occult metastases are found in upto 50 % of patients, although the incidence of occult level II nodes seems low. Our aim was to evaluate frozen section analysis-oriented elective level II PLND in patients with clinically node-negative (cN0) PTC. METHODS: This retrospective study included patients with cN0 PTC treated with total thyroidectomy and prophylactic bilateral central and lateral neck dissection of ipsilateral levels III and IV. Frozen section analysis of PLND III and IV was performed. If positive, the PLND was extended to level II. We measured the accuracy of frozen section analysis, the incidence of occult level II metastasis, and oncologic outcomes. RESULTS: A total of 295 patients were included. For frozen section analysis, the sensitivity was 71.0 %, specificity 99.6 %, positive predictive value 97.8 %, negative predictive value 92.4 %, overall accuracy 93.2 %. Definitive analysis found lateral node metastases in 63 of the 295(21 %) patients. Extension to level II was performed in 27 of 46 cases (59 %). Level II contained metastatic nodes in 12 of 27 (44 %) patients. There was no difference in total doses of 131I administered to patients with or without level II disease. Even when extension of PLND to level II was not performed, no cases of recurrent or persistent disease in level II occurred. CONCLUSIONS: Frozen section analysis was highly accurate.The rate of occult metastases in level II was low. Detection of additional metastases in level II did not modify subsequent treatment or the rate of recurrence and is not useful for routine application. PMID- 24231908 TI - [Glaucoma]. PMID- 24231909 TI - [Functional morphology of the outflow pathways of aqueous humor and their changes in open angle glaucoma]. AB - Aqueous humor exits the eye through the trabecular and uveoscleral outflow pathways. Under normal conditions intraocular pressure is maintained in the trabecular outflow pathways in which aqueous humor passes through the trabecular meshwork into Schlemm's canal. Intraocular pressure is generated through an outflow resistance in the juxtacanalicular region which consists of juxtacanalicular tissue and the inner wall endothelium of Schlemm's canal. The resistance of this region is under the influence of two contractile systems, the anterior longitudinal portion of the ciliary muscle and the contractile myofibroblast-like cells in the trabecular outflow pathways. Resistance is lowered through contraction of the ciliary muscle or relaxation of the contractile cells in the trabecular outflow pathways. In primary open angle glaucoma, resistance in the juxtacanalicular region is abnormally high. The cause of the increase is related to an increased activity in transforming growth factor beta and connective tissue growth factor signaling. The cells of the trabecular meshwork outflow pathways are stimulated to form a stronger contractile phenotype involving both an increase in the actin cytoskeleton and the surrounding fibrillar extracellular matrix. As a result there is an increase in cellular tone in the trabecular outflow pathways leading to an increase in rigidity and outflow resistance. PMID- 24231910 TI - [Structural diagnostics of course observation for glaucoma]. AB - BACKGROUND: Imaging of the structural progression of glaucoma enables measurement of the neuroretinal rim of the optic disc, retinal nerve fibre layer and thickness of the ganglion layer. METHODS: High resolution disc photography, laser scanning tomography, scanning laser polarimetry and optical coherence tomography (OCT) are the current methods of choice to document and measure progression of this chronic degenerative disease. RESULTS: Loss of the neuroretinal rim is only a few mm(2) or mm(3) per year and has to be differentiated from age-related loss which shows less change over the years. The most pronounced loss is temporal both superior and inferior. Thinning of the retinal nerve fibre layer follows the same pattern with significant annual changes of only 6-7 um. Modern OCT devices deliver measurements of the macula ganglion cell complex which can be even more sensitive than the thickness of the retinal nerve fibre layer. Qualitative criteria for structural progression are papillary hemorrhage, rarification of papillary vessels and specific changes of the retinal pigment epithelium. CONCLUSIONS: Structural loss due to glaucoma can be imaged and measured with different methods in different tissues. The evaluation of significant changes is still the responsibility of the ophthalmologist by taking all findings into account. PMID- 24231911 TI - [Practical aspects of glaucoma perimetry]. AB - Automatic static white-on-white perimetry is state of the art for the visual field examination of glaucoma patients. Full threshold measurements require at least 5 min. Careful instruction and supervision of the patient help to achieve high quality results. Alternative methods, such as the various types of flicker perimetry have a higher sensitivity and complement the early diagnosis. Attention must be paid to the specificity of these methods. Diagnosis may be difficult because the first changes do not have a typical topography. The typical examination interval for follow-up is 1 year but should be shorter in the beginning and in cases with deterioration. The evaluation of visual field development is highly important for glaucoma therapy control. Modern analysis programs offer excellent tools for this purpose. Some programs automatically detect learning effects and unreliable examinations. The change in global indices, e.g. median defect depth (MD), functional defect (FD) and visual field index (VFI) is plotted and statistically analyzed. Local trends are shown in symbol maps. Some programs calculate a prognosis of the future development of the visual field. PMID- 24231912 TI - [The Julius Springer prize for ophthalmology 2013: Dr. Corinne Huss honoured for exceptional ophthalmological work]. PMID- 24231913 TI - [Suspected tumor of the upper eyelid]. PMID- 24231914 TI - [Clarithromycin for monotherapy of B-cell MALT lymphoma?]. PMID- 24231915 TI - [Update on endocrine orbitopathy]. AB - Graves' orbitopathy is an autoimmune disease of the ocular adnex connective tissue and most commonly occurs together with Grave's hyperthyroidism. Anti-TSH receptor antibodies are specific for Graves' disease and are related to both the course of thyroid and orbital diseases. An active inflammatory disease stage is followed by an inactive stage of incomplete remission in most patients. Periorbital swelling, proptosis, diplopia and lid retraction severely impair the patients' quality of life. In the active state anti-inflammatory treatment consists of i.v. steroids, off-label use of immunomodulatory medication, selenium and in emergency cases orbital decompression. Fortunately, defects in inactive stable Graves' orbitopathy can be successfully treated by surgery and involve decompression for proptosis reduction, muscle recession to correct diplopia and (finally) lid surgery. PMID- 24231916 TI - [Communications of the DOG]. PMID- 24231918 TI - Mapping and validation of quantitative trait loci associated with concentrations of 16 elements in unmilled rice grain. AB - KEY MESSAGE: QTLs controlling the concentrations elements in rice grain were identified in two mapping populations. The QTLs were clustered such that most genomic regions were associated with more than one element. In this study, quantitative trait loci (QTLs) affecting the concentrations of 16 elements in whole, unmilled rice (Oryza sativa L.) grain were identified. Two rice mapping populations, the 'Lemont' * 'TeQing' recombinant inbred lines (LT-RILs), and the TeQing-into-Lemont backcross introgression lines (TILs) were used. To increase opportunity to detect and characterize QTLs, the TILs were grown under two contrasting field conditions, flooded and irrigated-but-unflooded. Correlations between the individual elements and between each element with grain shape, plant height, and time of heading were also studied. Transgressive segregation was observed among the LT-RILs for all elements. The 134 QTLs identified as associated with the grain concentrations of individual elements were found clustered into 39 genomic regions, 34 of which were found associated with grain element concentration in more than one population and/or flooding treatment. More QTLs were found significant among flooded TILs (92) than among unflooded TILs (47) or among flooded LT-RILs (40). Twenty-seven of the 40 QTLs identified among the LT-RILs were associated with the same element among the TILs. At least one QTL per element was validated in two or more population/environments. Nearly all of the grain element loci were linked to QTLs affecting additional elements, supporting the concept of element networks within plants. Several of the grain element QTLs co-located with QTLs for grain shape, plant height, and days to heading; but did not always differ for grain elemental concentration as predicted by those traits alone. A number of interesting patterns were found, including a strong Mg-P-K complex. PMID- 24231919 TI - Determination of heterotic groups for tropical Indica hybrid rice germplasm. AB - KEY MESSAGE: Two heterotic groups and four heterotic patterns were identified for IRRI hybrid rice germplasm to develop hybrid rice in the tropics based on SSR molecular data and field trials. Information on heterotic groups and patterns is a fundamental prerequisite for hybrid crop breeding; however, no such clear information is available for tropical hybrid rice breeding after more than 30 years of hybrid rice commercialization. Based on a study of genetic diversity using molecular markers, 18 parents representing hybrid rice populations historically developed at the International Rice Research Institute (IRRI) were selected to form diallel crosses of hybrids and were evaluated in tropical environments. Yield, yield heterosis and combining ability were investigated with the main objectives of (1) evaluating the magnitude of yield heterosis among marker-based parental groups, (2) examining the consistency between marker-based group and heterotic performance of hybrids, and (3) identifying foundational hybrid parents in discrete germplasm pools to provide a reference for tropical indica hybrid rice breeding. Significant differences in yield, yield heterosis and combining ability were detected among parents and among hybrids. On average, the hybrids yielded 14.8 % higher than the parents. Results revealed that inter group hybrids yielded higher, with higher yield heterosis than intra-group hybrids. Four heterotic patterns within two heterotic groups based on current IRRI B- and R-line germplasm were identified. Parents in two marker-based groups were identified with limited breeding value among current IRRI hybrid rice germplasm because of their lowest contribution to heterotic hybrids. Heterotic hybrids are significantly correlated with high-yielding parents. The efficiency of breeding heterotic hybrids could be enhanced using selected parents within identified marker-based heterotic groups. This information is useful for exploiting those widely distributed IRRI hybrid rice parents. PMID- 24231917 TI - Management of patients with resistant hypertension: current treatment options. AB - Resistant hypertension (RHTN) is an increasingly common clinical problem that is often heterogeneous in etiology, risk factors, and comorbidities. It is defined as uncontrolled blood pressure on optimal doses of three antihypertensive agents, ideally one being a diuretic. The definition also includes controlled hypertension with use of four or more antihypertensive agents. Recent observational studies have advanced the characterization of patients with RHTN. Patients with RHTN have higher rates of cardiovascular events and mortality compared with patients with more easily controlled hypertension. Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renovascular disease, are common in patients with RHTN and often coexist in the same patient. In addition, RHTN is often complicated by metabolic abnormalities. Patients with RHTN require a thorough evaluation to confirm the diagnosis and optimize treatment, which typically includes a combination of lifestyle adjustments, and pharmacologic and interventional treatment. Combination therapy including a diuretic, a long-acting calcium channel blocker, an angiotensin converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist where warranted is the classic regimen for patients with treatment resistant hypertension. Mineralocorticoid receptor antagonists like spironolactone or eplerenone have been shown to be efficacious in patients with RHTN, heart failure, chronic kidney disease, and primary aldosteronism. Novel interventional therapies, including baroreflex activation and renal denervation, have shown that both of these methods may be used to lower blood pressure safely, thereby providing exciting and promising new options to treat RHTN. PMID- 24231920 TI - Identification of putative quantitative trait loci associated with a flavonoid related to resistance to cabbage seedpod weevil (Ceutorhynchus obstrictus) in canola derived from an intergeneric cross, Sinapis alba * Brassica napus. AB - KEY MESSAGE: Kaempferol 3- O -sinapoyl-sophoroside 7- O -glucoside was putatively identified as the major component of a characteristic HPLC peak previously correlated with the reduction of cabbage seedpod weevil larval infestation in a novel canola genotype. The cabbage seedpod weevil (Ceutorhynchus obstrictus [Marsham]) (CSPW) is a serious pest of brassicaceous oilseed crops such as canola in both Europe and more recently in North America. At present, the only control strategy against CSPW is the application of insecticides. As an alternative more environmentally-friendly control strategy, we developed novel canola germplasm resistant to weevil attack through introgression of Sinapis alba DNA into Brassica napus by making the wide cross followed by embryo rescue and backcrossing to the B. napus parent. We have previously characterized resistant canola lines by metabolic profiling and were able to correlate reduction of larval infestation to the presence of a characteristic HPLC peak. In this study, we have putatively identified the major component in the peak using mass spectrometry as kaempferol 3-O-sinapoyl-sophoroside 7-O-glucoside (KSSG). We have also identified quantitative trait loci (QTL) associated with this HPLC peak in a mapping population consisting of more than 200 individual doubled haploid (DH) lines derived from a cross between CSW428 (the resistant parent) and SC030686 (the susceptible parent). This QTL accounted for approximately 9.5 % of the phenotypic variation in KSSG content. The observation that only one QTL was identified as surpassing the LOD threshold of 3.0 suggests that both parents may possess the positive alleles for other QTL that have not been detected in our study. This finding also indicates a complex regulatory mechanism for KSSG levels and provides an appropriate explanation for the large transgressive segregation observed in the DH lines of the QTL mapping population. PMID- 24231921 TI - Identification of genome regions controlling cotyledon, pod wall/seed coat and pod wall resistance to pea weevil through QTL mapping. AB - Pea weevil, Bruchus pisorum, is one of the limiting factors for field pea (Pisum sativum) cultivation in the world with pesticide application the only available method for its control. Resistance to pea weevil has been found in an accession of Pisum fulvum but transfer of this resistance to cultivated pea (P. sativum) is limited due to a lack of easy-to-use techniques for screening interspecific breeding populations. To address this problem, an interspecific population was created from a cross between cultivated field pea and P. fulvum (resistance source). Quantitative trait locus (QTL) mapping was performed to discover the regions associated with resistance to cotyledon, pod wall/seed coat and pod wall resistance. Three major QTLs, located on linkage groups LG2, LG4 and LG5 were found for cotyledon resistance explaining approximately 80 % of the phenotypic variation. Two major QTLs were found for pod wall/seed coat resistance on LG2 and LG5 explaining approximately 70 % of the phenotypic variation. Co-linearity of QTLs for cotyledon and pod wall/seed coat resistance suggested that the mechanism of resistance for these two traits might act through the same pathways. Only one QTL was found for pod wall resistance on LG7 explaining approximately 9 % of the phenotypic variation. This is the first report on the development of QTL markers to probe Pisum germplasm for pea weevil resistance genes. These flanking markers will be useful in accelerating the process of screening when breeding for pea weevil resistance. PMID- 24231922 TI - Generation and reactivity of o-carborynes. AB - o-Carboryne (1,2-dehydro-o-carborane) is a very reactive intermediate that can be generated in situ from 1-Br-2-Li-1,2-C2B10H10, 1-I-2-Li-1,2-C2B10H10 or 1-Me3Si-2 [IPh(OAc)]-1,2-C2B10H10. It exists in two resonance forms, a bonding form vs. a biradical form. Each form demonstrates unique reactivity patterns. o-Carboryne can undergo various types of reactions such as [4 + 2]/[2 + 2] cycloaddition, ene reaction, hydrogen abstraction, and sp(2)/sp(3) C-H bond insertion reaction with a broad spectrum of substrates including alkenes, alkynes, (hetero)aromatics, ethers, and ferrocenes. It is a very useful synthon for generating a variety of functionalized carboranes that have potential applications in medicine, materials science and organometallic/coordination chemistry. This perspective offers an overview of recent advances in this interesting research field. PMID- 24231923 TI - Synthetic cathinones: chemical phylogeny, physiology, and neuropharmacology. AB - This mini-review summarizes the history of cathinone and its synthesized derivatives from early records to the present day, including the appearance of synthetic cathinones in the drug combination known as bath salts. Bath salts may consist of one compound (MDPV) or combinations of MDPV and one or more other synthetic cathinones, which may also appear alone without MDPV. We briefly review recent in vitro studies of bath salts components alone or in combination, focusing on pharmacological and biophysical studies. Finally we summarize new data from in vivo procedures that characterize the abuse-related neurochemical and behavioral effects of synthetic cathinones in rats. PMID- 24231924 TI - High-detectivity nanowire photodetectors governed by bulk photocurrent dynamics with thermally stable carbide contacts. AB - Photodetectors fabricated from one-dimensional semiconductors are always dominated by the surface states due to their large surface-to-volume ratio. Therefore, the basic 5S requirements (high sensitivity, high signal-to-noise ratio, high spectral selectivity, high speed, and high stability) for practical photodetectors are difficult to satisfy. We report on high-temperature and high detectivity solar-blind deep-ultraviolet (DUV) photodetectors based on beta-Ga2O3 nanowires, in which the photoresponse behavior is dominated by the bulk instead of the surface states. Ohmic contact to the beta-Ga2O3 nanowires was achieved by using a thermally stable tungsten carbide electrode. As a result, the DUV responsivity at 250 nm shows the highest values--4492 A W(-1) at room temperature (RT) and 3000 A W(-1) at 553 K (280 degrees C)--among the DUV photodetectors. The detectivity is as high as 1.26*10(16) cm Hz(1/2) W(-1) at RT, and still remains 4.1*10(14) cm Hz(1/2) W(-1) at as high a temperature as 553 K. The photocurrent dynamics from the beta-Ga2O3 nanowire is discussed in terms of the bulk dominated photoresponse behavior. Other wide bandgap DUV detectors based on nanostructures could also be developed for high-temperature applications based on this work. PMID- 24231925 TI - Protocol-based treatment of hypertension: a critical step on the pathway to progress. PMID- 24231926 TI - A study on gingival enlargement and folic acid levels in phenytoin-treated epileptic patients: Testing hypotheses. AB - BACKGROUND: There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the antiepileptic therapy in the prevention of antiepileptic drug-induced gingival enlargement. However, studies in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy. The statistical analysis was done using t-test and the baseline serum folate levels and the serum folate levels obtained after 6 months of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. METHODS: A total of 25 patients aged between 18 and 50 years, clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was done prior to the start of and after 6 months of phenytoin therapy. RESULTS: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin-induced gingival enlargement. CONCLUSIONS: The results of the study suggest a higher incidence of gingival enlargement in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases. PMID- 24231927 TI - Ankle kinematics and muscle activity in functional ankle instability. AB - OBJECTIVE: Following an ankle injury, many patients have functional ankle instability (FAI) with an increased predisposition to reinjury. The purpose of this study was to assess the effects of FAI on ankle kinematics and muscle activity during a lateral hop movement. DESIGN: Cross-sectional and observational study; all data collection for each subject was performed on 1 day. SETTING: Clinical biomechanics laboratory. PATIENTS: Two groups were studied: (1) Control group-no ankle injury (n = 12), and (2) FAI group (n = 12). INTERVENTIONS: The lateral hop movement consisted of multiple lateral and medial 1-legged hops over an obstacle (width, 72.5 cm; depth, 25.5 cm; height, 14.3 cm) onto adjacent force platforms. Each subject was instructed to perform as many lateral hops as possible during the 6-second trial. Means, SDs, 95% confidence intervals of the differences, and P-values were calculated. MAIN OUTCOME MEASURES: Ankle kinematics and muscle activity throughout the lateral hop movement. RESULTS: Significant differences existed between groups for mean (SD) dorsiflexion ankle positions--FAI 82.4 degrees (6.4) versus normal 75.2 degrees (10.1) and tibialis anterior normalized muscle activity--FAI 0.27 (0.21) versus normal 0.16 (0.13) at ground contact. CONCLUSIONS: The FAI group revealed greater tibialis anterior muscle activity and dorsiflexion ankle position at contact moving in the lateral direction. These differences between groups may have been related to an inherent predisposition to ankle injuries, a preexisting difference in task performance, a consequence of injuries, or a compensatory adaptation to previous injuries. PMID- 24231928 TI - The preparticipation physical evaluation: an analysis of clinical practice. AB - OBJECTIVE: To evaluate current preparticipation physical evaluation (PPE) clinical practice behaviors. DESIGN: Telephone and Web-based survey study with attention to utilization of the Fourth Edition PPE Monograph. SETTING: We contacted the Washington State American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP) chapters, all Washington State high school athletic directors (ADs), and every state high school athletic association. INTERVENTIONS: Data collection and analysis regarding clinical practice. MAIN OUTCOME MEASURES: Awareness and utilization of the Fourth Edition PPE Monograph. RESULTS: The response rate was 72% (559/776) from the AAP, 56% (554/990) from the AAFP, 75% (317/424) from the ADs, and 100% (50/50) from the state athletic associations. Few physicians (37%) and ADs (6%) reported an awareness of the PPE Monograph. Knowledge of the Monograph did not vary by physician type, practice/school location, or experience (P > 0.05). Reported obstacles to the delivery of the PPE included time with patient (56%) and the lack of a standard form (52%). Physician awareness of the Monograph reduced the perception of obstacles (P < 0.01). Athletic directors reported financial limitations of the family as the primary obstacle (62%). Adoption of a single statewide PPE form was well supported (96% of physicians and 67% of ADs). Nationally, only 46% of state athletic associations mandate a single form, and only 16% use a form consistent with the Fourth Edition PPE Monograph. CONCLUSIONS: The medical community is largely unaware of national screening guidelines. New directions for education and policy are necessary to improve this implementation gap. PMID- 24231929 TI - Soccer boots elevate plantar pressures in elite male soccer professionals. AB - OBJECTIVE: The present study measured the difference in peak plantar pressure between running shoes and soccer shoes in male soccer professionals [mean (SD): age, 23 (4) years; height, 184 (7) cm; weight, 81 (6) kg]. DESIGN: Case series. SETTING: Institutional study. PARTICIPANTS: A total of 17 elite male soccer professionals [mean (SD): age, 23 (4) years; height, 184 (7) cm; weight 81 (6) kg]. INTERVENTIONS: Fifteen right and left steps with sensor-loaded insoles (99 sensors, 50 Hz) while running (3.3 m/s) in running shoes and then chosen soccer shoes (12-stud profile). The players were equipped with running shoes from the supplier without any medical supervision. MAIN OUTCOME MEASURES: Changes of peak plantar pressure for 9 defined foot portions between soccer boots and running shoes. RESULTS: A statistically significant increase of peak plantar pressure was found for the lateral midfoot (P < 0.001 for preferred and nonpreferred foot), the first metatarsal head (preferred foot: P < 0.001, nonpreferred foot: P = 0.002), the metatarsal heads 4/5 (preferred foot: P = 0.001, nonpreferred foot: P = 0.002), and the big toe (preferred foot: P = 0.001, nonpreferred foot: P < 0.001), but not for the lateral and medial hindfoot, the medial midfoot, and lesser toes. CONCLUSIONS: In running, soccer boots generate excessive foot loadings predominantly under the lateral midfoot, as compared with running shoes. Players should be trained with a thoughtfully designed workout regimen that allows performing as many straight running exercises as possible in running shoes instead of soccer boots. This may help to prevent fifth metatarsal stress fractures in elite male soccer players. PMID- 24231930 TI - Platelet-rich plasma in the management of articular cartilage pathology: a systematic review. AB - OBJECTIVE: Using systematic review methodology, we endeavored to answer the following questions concerning the treatment of osteochondral pathology: (1) what pathologies have been treated in vivo with the use of platelet-rich plasma (PRP); (2) what methods of PRP preparation and delivery have been reported; (3) what assessment tools and comparison group have been used to assess its effectiveness; and (4) what are the clinical outcomes of its use. DATA SOURCES: A systematic literature search was performed of the OVID, EMBASE, and Evidence Based Medicine Reviews databases to identify all studies published up to October 2012 that assessed clinical outcomes of the use of PRP for the treatment of chondral and osteochondral pathology, excluding those including concomitant management of acute fractures or ligament reconstruction. DATA EXTRACTION: The included studies were reviewed and the following data were extracted and tabulated: study authors' year and journal, study design and level of evidence, pathology treated, methods of PRP preparation and delivery, and clinical outcome scores. DATA SYNTHESIS: Ten studies were included in the final analysis. The majority of studies assessed the use of PRP in the treatment of degenerative osteoarthritis of the knee or hip (representing 570 of a total of 662 joints). The majority of patients were treated with intra-articular injections, whereas 2 studies used PRP as an adjunct to surgical treatment. Significant improvements in joint-specific clinical scores (7 of 8 studies), general health scores (4 of 4 studies), and pain scores (4 of 6 studies) compared with baseline were reported up to 6-month follow-up, but few studies provided longer-term data. No studies reported worse scores compared with baseline at final follow-up. Three of 4 comparative studies reported significantly better clinical and/or pain scores when compared with hyaluronic acid injections at similar follow-up times. CONCLUSIONS: Currently, there is a paucity of data supporting the use of PRP for the management of focal traumatic osteochondral defects. There is limited evidence suggesting short-term clinical benefits with the use of PRP for symptomatic osteoarthritis of the knee, but the studies published to date are of poor quality and at high risk for bias. Further high-quality comparative studies with longer follow-up are needed to ascertain whether PRP is beneficial, either alone or as an adjunct to surgical procedures, in the management of articular cartilage pathology. PMID- 24231931 TI - Bilateral knee and intermittent elbow pain in a competitive archer/hunter: phosphodiesterase-5-inhibitor-statin interaction? AB - A 59-year-old white hunter and archer presented to the sports medicine clinic with bilateral knee and left elbow pain. Various treatments for presumed musculoskeletal diagnoses did not help. When reviewing his medications, the patient concluded that the only new one before the appearance of his symptoms was tadalafil. He stopped taking it, and his pain resolved immediately thereafter. On review, it was noted that the patient was also on pravastatin. There have been a few previous reports of myopathy and rhabdomyolysis with the concomitant use of a phosphodiesterase-5 inhibitor (PDE5I), such as tadalafil and a statin. We report a case where such processes may have been occurring and may have resolved shortly after discontinuing concomitant use, in turn resulting in decreased pain. Clinicians may need to be aware of the possibility of such symptoms and processes occurring in patients taking both a statin and a PDE5I. PMID- 24231932 TI - Clinical usefulness with the combination of color Doppler and contrast-enhanced harmonic EUS for the assessment of visceral vascular diseases. AB - GOALS: To evaluate the clinical usefulness of the color Doppler and contrast enhanced harmonic endoscopic ultrasonography (CEH-EUS) in diagnosing visceral vascular diseases and in assessing morphologic and hemodynamic characteristics required for optimized patient management. BACKGROUND: Mesenteric arteries are easily accessible with EUS because of its proximities to the gastrointestinal tract. STUDY: EUS was performed in 12 patients with clinically suspected visceral vascular disease, as determined by computed tomography (CT) scan between February 2012 and March 2013. Conventional B-mode, color Doppler, and CEH-EUS was performed to evaluate vascular status of the celiac artery and superior mesenteric artery (SMA). RESULTS: CT scan imaging suggested arterial dissection in 9 patients; arterial stenosis or occlusion in 2 patients, and periarterial soft tissue cuffing in 1 patient. EUS accurately identified all the visceral vascular lesions of 11 patients and 1 patient with suspected SMA dissection on CT imaging was proven to be normal by EUS. EUS also identified one undefined dissection not detected on abdominal CT. EUS examination revealed vascular intimal flap in 5 patients and blood flow within the true lumen and thrombi within the false lumen in 8 patients. In addition, the stenotic area could be calculated using color Doppler EUS. Two patients underwent surgical thrombectomy and angioplasty because of total occlusion of SMA on color Doppler and CEH-EUS. CONCLUSIONS: The combination of color Doppler and CEH-EUS may be a promising diagnostic modality to assess the splanchnic artery without exposure to radiation. Moreover, EUS is a useful tool to determine the appropriate treatment options for patients with isolated mesenteric artery dissection. PMID- 24231933 TI - Savary dilation is a safe and effective long-term means of treatment of symptomatic cricopharyngeal bar: a single-center experience. AB - GOALS: Dilation of a cricopharyngeal (CP) bar can be a safe and effective means of nonsurgical treatment as elderly patient population has high morbidity and is at a higher risk of surgical complications. BACKGROUND: CP bar is a relatively uncommon radiologic finding, which is an infrequent cause of oropharyngeal dysphagia in the elderly population. METHODS: Patients were included in study from January 2007 to January 2012, if their dysphagia was solely attributed to CP bar on predilation radiologic imaging by either modified barium swallow or barium esophagogram. A functional outcome swallowing score (FOSS) was calculated at 1, 4, and 6 months from initial and last dilation performed. RESULTS: A total of 31 patients with a mean age of 71.65 (54 to 88) years and mean body mass index 27.81 (15 to 41) were included in the study. Over the time period of 5 years, a total of 53 dilations were performed. The median predilation FOSS was 3. The median postdilation FOSS was 1 at the end of 6 months from last dilation performed. There were no immediate or remote complications. CONCLUSIONS: On follow-up from first dilation, 65% patients had statistically significant improvement in FOSS lasting for at least 6 months. Savary dilation seems to be a safe and effective treatment for symptomatic CP bar patients. PMID- 24231934 TI - Incidence and risk factors of delayed postpolypectomy bleeding: a retrospective cohort study. AB - BACKGROUND/AIM: Delayed bleeding is a serious complication that occurs after polypectomy. Many risk factors for delayed bleeding have been suggested, but there is little analysis of procedure-related risk factors. The purpose of this study is to identify a wide range of risk factors for delayed postpolypectomy bleeding (DPPB) and analyze the correlations of those potential DPPB risk factors. MATERIALS AND METHODS: In this retrospective cohort study, 5981 polypectomies in 3788 patients were evaluated between January 2010 and February 2012. Patient-related, polyp-related, and procedure-related factors were evaluated as potential DPPB risk factors. RESULTS: Delayed bleeding occurred in 42 patients (1.1%). Multivariate analysis revealed that polyp size >10 mm [odds ratio (OR), 2.785; 95% confidence interval (CI), 1.406-5.513; P=0.003], location in the right hemi-colon (OR, 2.289; 95% CI, 1.117-4.693; P=0.024), and endoscopist's experience (<300 total cases of colonoscopy performed; OR, 4.803; 95% CI, 2.631-8.766; P=0.001) were significant risk factors for DPPB. Especially protruded type polyps (Ip, Isp) larger than 1 cm in the right-side colon were associated with increased risk. Right-side polypectomy by a nonexpert endoscopist was a significant risk factor for DPPB, especially with procedures in the cecum area. Taking the 1.5% DPPB incidence as cutoff value, the learning curve of colonoscopic polypectomy may be estimated as 400 cases of polypectomy. CONCLUSIONS: Polyp size, endoscopist's experience, and right hemi-colon location were identified as potential risk factors for DPPB development. PMID- 24231935 TI - Metabolic syndrome associated with primary biliary cirrhosis. AB - INTRODUCTION: Primary biliary cirrhosis (PBC) is characterized by a long natural history and a low incidence of cardiovascular events despite high serum cholesterol levels. The role of any metabolic conditions (obesity, hypertension, diabetes) in association with PBC has not been analyzed, however. AIM: : To assess the influence of metabolic syndrome (MS) on response to ursodeoxycholic acid (UDCA) and the survival in PBC patients. METHODS: The historical database (1975 to 2011) comprising consecutively enrolled PBC patients with a mean follow up of 123 months (range, 12 to 425 mo) was used. All patients were treated with UDCA (15 mg/kg/d). Responders to UDCA were defined as patients achieving at least a 40% drop in their alkaline phosphatase levels after 1 year. MS was defined according to the American Heart Association criteria. Survival was analyzed by means of Kaplan-Meier curves. RESULTS: A total of 171 PBC patients were eligible for the study; 55 of them (32.1%) fulfilled the criteria for MS at presentation. Liver function tests and Mayo score were found comparable in PBC patients with and without MS. Histologic stages were similar in the 2 groups at the baseline. Significantly more cardiovascular events occurred in patients with MS during the follow-up (P<0.0001). Response to UDCA was greater in the group without MS, but the difference was not statistically significant. The Kaplan-Meier curves were similar in the 2 groups. CONCLUSIONS: When associated with MS, PBC should be monitored carefully due to the risk of cardiovascular events. PMID- 24231936 TI - When and how was the new round of increase in inflammatory bowel disease in the United States started? PMID- 24231937 TI - Spleen-preserving distal pancreatectomy or distal pancreatectomy with splenectomy?: Perioperative and patient-reported outcome analysis. AB - GOALS: We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. BACKGROUND: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. STUDY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses, estimated blood loss, intraoperative transfusion, and operative time between the 2 groups. More perioperative complications occurred in the DPS group than in the SPDP group (P=0.0344). Consequently, postoperative hospital stay was significantly shorter in the SPDP group than in the DPS group (P=0.0273). In the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (P=0.047). More patients in the DPS group felt fatigue (P=0.0481) and poor health condition (P=0.0371). Less newly developed (P=0.0193) and aggravated diabetes mellitus (P=0.0361) were also observed in the SPDP group. Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts, and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher grade complications, prolonged hospital stays, and severe hematological abnormalities, DPS seemed to result in poor health condition based on the follow up survey. Even an effort to preserve an adult spleen in distal pancreatectomy is worthwhile. PMID- 24231940 TI - Reproductive toxicity evaluation of the dental resin monomer bisphenol a glycidyl methacrylate (CAS 1565-94-2) in mice. AB - The reproductive toxicity potential of the dental resin monomer bisphenol A glycidyl methacrylate (BisGMA; CASRN 1565-94-2) was investigated in male and female Crl: CD1(ICR) mice, 4 dosage groups, and 25 mice/sex/group. Formulations of BisGMA (0, 0.008, 0.08, or 0.8 mg/kg/d) in 0.8% ethanol in deionized water were intubated once daily beginning 28 days before cohabitation and continuing through mating (males) or through gestation day 17. The following parameters were evaluated: viability, clinical signs, body weights, estrous cyclicity, necropsy observations, organ weights, sperm concentration/motility/morphology, cesarean sectioning and litter observations, and histopathological evaluation of select tissues. No deaths or clinical signs related to BisGMA occurred. No significant changes in male and female body weights and body weight gains were recorded at any of the administered dosages of BisGMA. All mating and fertility parameters, and all litter and fetal data, were considered to be unaffected by dosages of BisGMA as high as 0.8 mg/kg/d. Gross or histopathologic tissue changes attributable to the test article were not observed. Reproductive and developmental no observed effect levels (NOAELs) for BisGMA were 0.8 mg/kg/d, the highest dose tested. Comparison of this NOAEL value to published probabilistic estimates of human BisGMA exposure from dental products suggests a margin of safety of at least 280- to nearly 2000-fold. Under the conditions of this study, BisGMA is not a reproductive toxicant. PMID- 24231941 TI - Unseen battles: the recognition, assessment, and treatment issues of men with military sexual trauma (MST). AB - While there is increasing attention on sexual violence in the military, the focus has been primarily on women. There is very little information regarding the effects of and treatment for men who experience military sexual trauma (MST). The aim of this article is to consolidate the known information about men with MST including prevalence rates, factors that affect those rates, gender differences, medical and psychiatric sequelae, and finally a review of two experimental studies. Implications for future research, practice, and policy are also discussed. PMID- 24231942 TI - Should child obesity be an issue for child protective services? A call for more research on this critical public health issue. AB - Given the lasting effects on adolescent and adult health, childhood obesity is a major public health issue. The relatively slow progress toward the prevention and treatment of childhood obesity, however, has prompted leaders in both academic and practice sectors to advocate for what may be considered a radical intervention approach, to conceptualize extreme child obesity as an issue of child maltreatment. Advocates of this approach suggest that this conceptualization affords a new angle for intervention-the involvement of child protective services (CPS) in mandating family-focused lifestyle changes aimed at reducing child overweight and, in the most extreme cases, the removal of the obese child from the home. However, surprisingly little research has been conducted to inform policies or practices consistent with this recommendation, which is already being implemented in some states. This article aims to provide an overview of the challenges to the prevention and treatment of childhood obesity that have motivated the call for CPS involvement in extreme cases and to review the existing research related to this approach. Given that relatively little data are currently available to support or refute the merits of CPS involvement, recommendations for future research that would better inform public policy and decision making regarding this and other intervention strategies are also highlighted. PMID- 24231943 TI - Cystic Fibrosis Patents: A Case Study of Successful Licensing. AB - From 2006-2010, Duke University's Center for Public Genomics prepared eight case studies examining the effects of gene patent licensing practices on clinical access to genetic testing for ten clinical conditions. One of these case studies focused on the successful licensing practices employed by the University of Michigan and the Hospital for Sick Children in Toronto for patents covering the CFTR gene and its DeltaF508 mutation that causes a majority of cystic fibrosis cases. Since the licensing of these patents has not impeded clinical access to genetic testing, we sought to understand how this successful licensing model was developed and whether it might be applicable to other gene patents. We interviewed four key players who either were involved in the initial discussions regarding the structure of licensing or who have recently managed the licenses and collected related documents. Important features of the licensing planning process included thoughtful consideration of potential uses of the patent; anticipation of future scientific discoveries and technological advances; engagement of relevant stakeholders, including the Cystic Fibrosis Foundation; and using separate licenses for in-house diagnostics versus kit manufacture. These features led to the development of a licensing model that has not only allowed the patent holders to avoid the controversy that has plagued other gene patents, but has also allowed research, development of new therapeutics, and wide spread dissemination of genetic testing for cystic fibrosis. Although this licensing model may not be applicable to all gene patents, it serves as a model in which gene patent licensing can successfully enable innovation, investment in therapeutics research, and protect intellectual property while respecting the needs of patients, scientists, and public health. PMID- 24231945 TI - Large cerebellar mass lesion: A rare intracranial manifestation of blastomycosis. AB - BACKGROUND: Blastomyces dermatitidis is a dimorphic fungus found endemically in the Mississippi and Ohio River basins and in the Midwestern and Canadian provinces that border the Great Lakes. Unlike other fungal infections, it most commonly affects immunocompetent hosts. Blastomycosis typically manifests as pulmonary infection, but may affect nearly any organ, including the skin, bone, and genitourinary system. Central nervous system (CNS) blastomycosis is rare, but potentially fatal manifestation of this disease. When it does occur, it most commonly presents as acute or chronic meningitis. CASE DESCRIPTION: We present a case of a patient who suffered intractable nausea and vomiting for several months before discovery of a large cerebellar blastomycoma causing mass effect and obstructive hydrocephalus. The enhancing lesion with unusual peripheral cystic structures is a unique radiographic appearance of CNS blastomycosis. CONCLUSION: We review this patient's purely intraparenchymal manifestation of CNS blastomycosis and describe the unique imaging characteristics encountered. PMID- 24231946 TI - A reanalysis of cancer mortality in Canadian nuclear workers (1956-1994) based on revised exposure and cohort data. AB - BACKGROUND: A 15-country study of nuclear workers reported significantly increased radiation-related risks of all cancers excluding leukaemia, with Canadian data a major factor behind the pooled results. We analysed mortality (1956-1994) in the updated Canadian cohort and provided revised risk estimates. METHODS: Employment records were searched to verify and revise exposure data and to restore missing socioeconomic status. Excess relative risks per sievert (ERR/Sv) of recorded radiation dose and 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS: A significant heterogeneity of the dose-response for solid cancer was identified (P=0.02), with 3088 early (1956 1964) Atomic Energy of Canada Limited (AECL) workers having a significant increase (ERR/Sv=7.87, 95% CI: 1.88, 19.5), and no evidence of radiation risk for 42,228 workers employed by three nuclear power plant companies and post-1964 AECL (ERR/Sv=-1.20, 95% CI: <-1.47, 2.39). Radiation risks of leukaemia were negative in early AECL workers and non-significantly increased in other workers. In analyses with separate terms for tritium and gamma doses, there was no evidence of increased risk from tritium exposure. All workers had mortality lower than the general population. CONCLUSION: Significantly increased risks for early AECL workers are most likely due to incomplete transfer of AECL dose records to the National Dose Registry. Analyses of the remainder of the Canadian nuclear workers (93.2%) provided no evidence of increased risk, but the risk estimate was compatible with estimates that form the basis of radiation protection standards. Study findings suggest that the revised Canadian cohort, with the exclusion of early AECL workers, would likely have an important effect on the 15-country pooled risk estimate of radiation-related risks of all cancer excluding leukaemia by substantially reducing the size of the point estimate and its significance. PMID- 24231947 TI - Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy. AB - BACKGROUND: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. METHODS: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. RESULTS: Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (~80%) and 6-month OS (~60%) probability than level >= 80. CONCLUSION: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability. PMID- 24231948 TI - The correlation between cell-free DNA and tumour burden was estimated by PET/CT in patients with advanced NSCLC. AB - BACKGROUND: Cell-free DNA (cfDNA) circulating in the blood holds a possible prognostic value in malignant diseases. Under malignant conditions, the level of cfDNA increases but the biological mechanism remains to be fully understood. We aimed to examine the correlation between cfDNA and total tumour burden defined by positron emission tomography (PET) parameters. METHODS: Patients with advanced non-small cell lung cancer (NSCLC) were enrolled into a prospective biomarker trial. Before treatment, plasma was extracted and the level of cfDNA was determined by qPCR. An (18)F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) scan was performed and evaluated in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Tumour contours were delineated semi-automatically by a threshold standardised uptake value (SUV) of 2.5. The primary end point was correlation among cfDNA, MTV and TLG. The secondary end point was overall survival (OS) according to cfDNA, MTV and TLG. RESULTS: Fifty three patients were included. There were no correlations between cfDNA and MTV (r=0.1) or TLG (r=0.1). cfDNA >75th percentile was correlated with shorter OS (P=0.02), confirmed in a multivariate analysis. MTV>the median was associated with a significantly shorter OS (P=0.02). There was no significant difference in OS according to TLG (P=0.08). CONCLUSION: Cell-free DNA may not be a simple measure of tumour burden, but seems to reflect more complex mechanisms of tumour biology, making it attractive as an independent prognostic marker. PMID- 24231949 TI - p53-Based cyclotherapy: exploiting the 'guardian of the genome' to protect normal cells from cytotoxic therapy. AB - Side effects of chemotherapy are a major impediment in the treatment of cancer. Cyclotherapy is an emerging therapeutic strategy for protecting normal cells from the side effects of chemotherapy. Low, non-genotoxic doses of known p53 activators can be used to induce p53-dependent cell cycle arrest in normal cells bearing wild-type p53. This cytostatic effect of p53 can protect normal cells from the toxicity of S- or M-phase poisons. Here, we have reviewed existing cyclotherapy regimens using two well-known p53 activators, nutlin-3 and actinomycin D. We have highlighted an exemplar clinical perspective for cyclotherapy in breast cancer. The recent development of novel stapled peptides as activators of p53 without the corresponding cytotoxicity holds great promise for cyclotherapy to enhance the therapeutic window of existing chemotherapy drugs. PMID- 24231950 TI - Nuclear worker studies: promise and pitfalls. PMID- 24231951 TI - Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair. AB - BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I gammaH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell cycle control as well as HR pathway. PMID- 24231952 TI - An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes. AB - BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1alpha (Hif-1alpha), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1-5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan-Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16-82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1alpha and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1alpha expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1alpha-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1alpha+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif 1alpha expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up. PMID- 24231953 TI - Collagen type XI alpha1 facilitates head and neck squamous cell cancer growth and invasion. AB - BACKGROUND: Although it is well established that the extracellular matrix affects tumour progression, not much is known about the various components and their effect on head and neck squamous cell carcinoma (HNSCC) progression. Levels of collagen type XI alpha1 (colXIalpha1), a minor fibrillar collagen, have been shown to be increased in tumour compared with normal tissue in several cancers, including colorectal, breast, and non-small cell lung cancer. Currently, the functional significance of colXIalpha1 is not understood. METHODS: We examined the expression levels of colXIalpha1 mRNA and elucidated the functional role of colXIalpha1 in HNSCC. Cell proliferation, invasion, and migration were examined with and without colXIalpha1 knockdown with siRNA in HNSCC cells. RESULTS: Our data demonstrate that colXIalpha1 expression is increased in tumour samples compared with levels in normal adjacent tissue in 16/23 HNSCC patients. In addition, colalpha11 is increased in HNSCC cell lines compared with normal immortalised epithelial cells and is increased in tumour-derived fibroblasts compared with normal fibroblasts. Using an siRNA approach, we demonstrate that colXIalpha1 contributes to proliferation, migration, and invasion of HNSCC. CONCLUSION: Our cumulative findings suggest that colXIalpha1 contributes to HNSCC tumorigenesis and may serve as a potential therapeutic target. PMID- 24231954 TI - Preoperative nomogram for the identification of lymph node metastasis in early cervical cancer. AB - BACKGROUND: The objective of this study is to construct a preoperative nomogram predicting lymph node metastasis (LNM) in early-cervical cancer patients. METHODS: Between 2009 and 2012, 493 early-cervical cancer patients received hysterectomy and pelvic/para-aortic lymphadenectomy. Patients who were diagnosed during 2009-2010 were assigned to a model-development cohort (n=304) and the others were assigned to a validation cohort (n=189). A multivariate logistic model was created from preoperative clinicopathologic data, from which a nomogram was developed and validated. A predicted probability of LNM<5% was defined as low risk. RESULTS: Age, tumour size assessed by magnetic resonance imaging, and LNM assessed by positron emission tomography/computed tomography were independent predictors of nodal metastasis. The nomogram incorporating these three predictors demonstrated good discrimination and calibration (concordance index=0.878; 95% confidence interval (CI), 0.833-0.917). In the validation cohort, the discrimination accuracy was 0.825 (95% CI, 0.736-0.895). In the model-development cohort, 34% of them were classified as low risk and negative predictive value (NPV) was 99.0%. In the validation cohort, 38% were identified as low risk and NPV was 95.8%. Integrating the model-development and validation cohorts, negative likelihood ratio was 0.094 (95% CI, 0.036-0.248). CONCLUSION: A robust nomogram predicting LNM in early cervical cancer was developed. This model may improve clinical trial design and help physicians to decide whether lymphadenectomy should be performed. PMID- 24231955 TI - Breast lesions in reduction mammaplasty specimens: a histopathological pattern in 534 patients. AB - BACKGROUND: The prevalence of breast lesions (benign, precancerous and cancer lesions) in reduction mammaplasty (RM) specimens has rarely been reported in Europe and never in the Swiss population. METHODS: Personal and histopathological data from 534 female patients who underwent RM were reviewed. RESULTS: Benign and/or malignant lesions were detected in 76.2% of all patients. Benign breast lesions associated with an increased risk of developing breast cancer represented 2.8% of all lesions. Breast cancer in situ was identified in 5 (0.9%) patients. Patient age and previous history of breast cancer were risk factors for incidental breast cancer. CONCLUSION: The rate of incidental carcinoma in situ was higher for patients with breast cancer history. Probably due to preoperative breast cancer investigation, no occult invasive breast cancer was found in reduction mammary specimens. Therefore before RM, breast cancer evaluation should be considered for all patients, especially for those with breast cancer risk factors (e.g., patient age, personal history of breast cancer). PMID- 24231957 TI - Comparison of models of post-hyperthermia cell survival. AB - Several existing mathematical models of the survival of mammalian cells in culture following heating are compared. These models describe the fraction of cells that survive in a normal culture environment following a relatively brief period of heating between approximately 43 degrees C and 60 degrees C. The models have been developed either from rate process or mechanistic arguments. Little quantitative comparison between such models has been made using the same sets of data. The models are compared using the Akaike Information Criterion (AICc) after the model parameters have been estimated for two sets of existing data: human prostate cancer cells and Chinese hamster ovary cells. Most of the models capture the cell survival response. Scaled sensitivity coefficients show that some of the models have parameters that are difficult to estimate reliably. Relatively small variations in the AICc suggest that more measurements are needed before ranking the models. PMID- 24231956 TI - An anti-leishmanial thiadiazine agent induces multiple myeloma cell apoptosis by suppressing the nuclear factor kappaB signalling pathway. AB - BACKGROUND: Nuclear factor kappaB (NFkappaB) has a critical role in the pathophysiology of multiple myeloma. Targeting NFkappaB is an important strategy for anti-myeloma drug discovery. METHODS: Luciferase assay was used to evaluate the effects of DETT on NFkappaB activity. Annexin V-PI double staining and immunoblotting were used to evaluate DETT-induced cell apoptosis and suppression of NFkappaB signalling. Anti-myeloma activity was studied in nude mice. RESULTS: DETT downregulated IKKalpha, beta, p65, and p50 expression and inhibited phosphorylation of p65 (Ser536) and IkappaBalpha. Simultaneously, DETT increased IkappaBalpha, an inhibitor of the p65/p50 heterodimer, even in the presence of stimulants lipopolysaccharide, tumour necrosis factor-alpha, or interleukin-6. DETT inhibited NFkappaB transcription activity and downregulated NFkappaB targeted genes, including Bcl-2, Bcl-XL, and XIAP as measured by their protein expression. Deregulation of NFkappaB signalling by DETT resulted in MM cell apoptosis characterised by cleavage of caspase-3, caspase-8, and PARP. Notably, this apoptosis was partly blocked by the activation of NFkappaB signalling in the presence of TNFalpha and IL-6. Moreover, DETT delayed myeloma tumour growth in nude mice without overt toxicity. CONCLUSION: DETT displays a promising potential for MM therapy as an inhibitor of the NFkappaB signalling pathway. PMID- 24231958 TI - Hydrodynamic interaction between a platelet and an erythrocyte: effect of erythrocyte deformability, dynamics, and wall proximity. AB - We present three-dimensional numerical simulations of hydrodynamic interaction between a red blood cell (RBC) and a platelet in a wall-bounded shear flow. The dynamics and large deformation of the RBC are fully resolved in the simulations using a front-tracking method. The objective is to quantify the influence of tank treading and tumbling dynamics of the RBC, and the presence of a bounding wall on the deflection of platelet trajectories. We observe two types of interaction: A crossing event in which the platelet comes in close proximity to the RBC, rolls over it, and continues to move in the same direction; and a turning event in which the platelet turns away before coming close to the RBC. The crossing events occur when the initial lateral separation between the cells is above a critical separation, and the turning events occur when it is below the critical separation. The critical lateral separation is found to be higher during the tumbling motion than that during the tank treading. When the RBC is flowing closer to the wall than the platelet, the critical separation increases by several fold, implying the turning events have higher probability to occur than the crossing events. On the contrary, if the platelet is flowing closer to the wall than the RBC, the critical separation decreases by several folds, implying the crossing events are likely to occur. Based on the numerical results, we propose a mechanism of continual platelet drift from the RBC-rich region of the vessel towards the wall by a succession of turning and crossing events. The trajectory deflection in the crossing events is found to depend nonmonotonically on the initial lateral separation, unlike the monotonic trend observed in tracer particle deflection and in deformable sphere-sphere collision. This nonmonotonic trend is shown to be a consequence of the deformation of the RBC caused by the platelet upon collision. An estimation of the platelet diffusion coefficient yields values that are similar to those reported in experiments and computer simulations with multicellular suspension. PMID- 24231959 TI - On the modeling of an intervertebral disc using a novel large deformation multi shell approach. AB - The objective of this study is to develop an analytical model to predict the stresses and displacements in the lamellae of the intervertebral disc subjected to a compressive force. This is achieved by developing a model based on membrane theory combined to large deformation multishell structural behavior. Equations for longitudinal and circumferential stresses are formulated for each lamella of the anulus fibrosus. Multilamellae interaction is a statically indeterminate problem, which requires equations of compatibility of the displacements of adjacent lamellae to be resolved. The large deformation inherent to soft tissue is considered and the solution is obtained using an iterative process. Elastic interactions with a large deformation is a novelty in analytical modeling of soft tissues. This provides model realism and offers the possibility for new and in depth investigations. Results are given for longitudinal and circumferential stresses and displacements as well as contact pressures for every lamella of the anulus fibrosus. The analytical results are compared to those of two finite element models. The results suggest that the most highly stressed zone is located on the innermost lamella. Stresses decrease through disc thickness and are at a maximum at the innermost lamella. Circumferential stress is predominant and the difference is less than 5% at any point of the anulus fibrosus when the analytical model is compared to the finite element model using coupled degrees of freedom at the lamellae interface. When compared to the finite element model using contact elements, the difference is below 11%. Contact pressures from the inside to the outside of the anulus fibrosus are shown to decrease nonlinearly. The model presented in this study has demonstrated that it is possible to analytically simulate the complex mechanical behavior of a multishell intervertebral disc subjected to compression, provided some simplifications. Further improvements are suggested to increase model realism and recommendations are given for future experimentation necessary to support both the analytical and numerical models. PMID- 24231960 TI - Mechanical response of the herniated human abdomen to the placement of different prostheses. AB - This paper describes a method designed to model the repaired herniated human abdomen just after surgery and examine its static mechanical response to the maximum intra-abdominal pressure provoked by a physiological movement (standing cough). The model is based on the real geometry of the human abdomen bearing a large incisional hernia with several anatomical structures differentiated by MRI. To analyze the outcome of hernia repair, the surgical procedure was simulated by modeling a prosthesis placed over the hernia. Three surgical meshes with different mechanical properties were considered: an isotropic heavy-weight mesh (Surgipro(r)), a slightly anisotropic light-weight mesh (Optilene(r)), and a highly anisotropic medium-weight mesh (Infinit(r)). Our findings confirm that anisotropic implants need to be positioned such that the most compliant axis of the mesh coincides with the craneo-caudal direction of the body. PMID- 24231961 TI - Confocal image-based computational modeling of nitric oxide transport in a rat mesenteric lymphatic vessel. AB - The lymphatic system plays important roles in protein and solute transport as well as in the immune system. Its functionality is vital to proper homeostasis and fluid balance. Lymph may be propelled by intrinsic (active) vessel pumping or passive compression from external tissue movement. With regard to the former, nitric oxide (NO) is known to play an important role modulating lymphatic vessel contraction and vasodilation. Lymphatic endothelial cells (LECs) are sensitive to shear, and increases in flow have been shown to cause enhanced production of NO by LECs. Additionally, high concentrations of NO have been experimentally observed in the sinus region of mesenteric lymphatic vessels. A computational flow and mass transfer model using physiologic geometries obtained from confocal images of a rat mesenteric lymphatic vessel was developed to determine the characteristics of NO transport in the lymphatic flow regime. Both steady and unsteady analyses were performed. Production of NO was shear-dependent; basal cases using constant production were also generated. Simulations revealed areas of flow stagnation adjacent to the valve leaflets, suggesting the high concentrations observed here experimentally are due to minimal convection in this region. LEC sensitivity to shear was found to alter the concentration of NO in the vessel, and the convective forces were found to profoundly affect the concentration of NO at a Peclet value greater than approximately 61. The quasisteady analysis was able to resolve wall shear stress within 0.15% of the unsteady case. However, the percent difference between unsteady and quasisteady conditions was higher for NO concentration (6.7%). We have shown high NO concentrations adjacent to the valve leaflets are most likely due to flow mediated processes rather than differential production by shear-sensitive LECs. Additionally, this model supports experimental findings of shear-dependent production, since removing shear dependence resulted in concentrations that are physiologically counterintuitive. Understanding the transport mechanisms and flow regimes in the lymphatic vasculature could help in the development of therapeutics to treat lymphatic disorders. PMID- 24231962 TI - An experimental and modeling study of the viscoelastic behavior of collagen gel. AB - The macroscopic viscoelastic behavior of collagen gel was studied through relaxation time distribution spectrum obtained from stress relaxation tests and viscoelastic constitutive modeling. Biaxial stress relaxation tests were performed to characterize the viscoelastic behavior of collagen gel crosslinked with Genipin solution. Relaxation time distribution spectrum was obtained from the stress relaxation data by inverse Laplace transform. Peaks at the short (0.3 s-1 s), medium (3 s-90 s), and long relaxation time (>200 s) were observed in the continuous spectrum, which likely correspond to relaxation mechanisms involve fiber, inter-fibril, and fibril sliding. The intensity of the long-term peaks increases with higher initial stress levels indicating the engagement of collagen fibrils at higher levels of tissue strain. We have shown that the stress relaxation behavior can be well simulated using a viscoelastic model with viscous material parameters obtained directly from the relaxation time spectrum. Results from the current study suggest that the relaxation time distribution spectrum is useful in connecting the macro-level viscoelastic behavior of collagen matrices with micro-level structure changes. PMID- 24231963 TI - Left ventricular finite element model bounded by a systemic circulation model. AB - A series of models were developed in which a circulatory system model was coupled to an existing series of finite element (FE) models of the left ventricle (LV). The circulatory models were used to provide realistic boundary conditions for the LV models. This was developed for the JSim analysis package and was composed of a systemic arterial, capillary, and venous system in a closed loop with a varying elastance LV and left atria to provide the driving pressures and flows matching those of the FE model. Three coupled models were developed, a normal LV under normotensive aortic loading (116/80 mm Hg), a mild hypertension (137/89 mm Hg) model, and a moderate hypertension model (165/100 mm Hg). The initial step in the modeling analysis was that the circulation was optimized to the end-diastolic pressure and volume values of the LV model. The cardiac FE models were then optimized to the systolic pressure/volume characteristics of the steady-state JSim circulatory model solution. Comparison of the stress predictions for the three models indicated that the mild hypertensive case produced a 21% increase in the average fiber stress levels, and the moderate hypertension case had a 36% increase in average stress. The circulatory work increased by 18% and 43% over that of the control for the mild and moderate hypertensive cases, respectively. PMID- 24231964 TI - One versus two implant-retained dentures: comparing biomechanics under oblique mastication forces. AB - The results from clinical tests of single implant-retained dentures (SIDs) are quite promising. However, the biomechanics of SIDs are still insufficiently determined. The aim of the study was to compare the implant loads and pressures beneath one and two implant-retained dentures (TIDs) under oblique mastication forces. The finite element method was used to conduct a model analysis in order to compare loading of the denture attachment onto the implant that accompanies oblique mastication forces in the cases of SIDs and TIDs. The possibility of a denture detaching and sliding on the mucous membrane surface was simulated. The SID solution faced a more remarkable tilt in the direction of the mastication forces, a higher pressures on the mucous membrane surface, and higher implant loadings. The hingelike restraints in the TID favored utilization of the support in the posterior area. The higher pressure values for the SID can be confusing and could lead to inaccurate conclusions about the acceptability of the SID. In the TID, the same areas of the mucous membrane were persistently loaded, independent of the occlusal force direction. In contrast, in the SID the full freedom of rotational movement enhances alternating use of the mucous membrane. This finding explains the more frequent sores in the mucous membrane beneath the TID than beneath the SID. PMID- 24231965 TI - Comparison of approaches to quantify arterial damping capacity from pressurization tests on mouse conduit arteries. AB - Large conduit arteries are not purely elastic, but viscoelastic, which affects not only the mechanical behavior but also the ventricular afterload. Different hysteresis loops such as pressure-diameter, pressure-luminal cross-sectional area (LCSA), and stress-strain have been used to estimate damping capacity, which is associated with the ratio of the dissipated energy to the stored energy. Typically, linearized methods are used to calculate the damping capacity of arteries despite the fact that arteries are nonlinearly viscoelastic. The differences in the calculated damping capacity between these hysteresis loops and the most common linear and correct nonlinear methods have not been fully examined. The purpose of this study was thus to examine these differences and to determine a preferred approach for arterial damping capacity estimation. Pressurization tests were performed on mouse extralobar pulmonary and carotid arteries in their physiological pressure ranges with pressure (P) and outer diameter (OD) measured. The P-inner diameter (ID), P-stretch, P-Almansi strain, P Green strain, P-LCSA, and stress-strain loops (including the Cauchy and Piola Kirchhoff stresses and Almansi and Green strains) were calculated using the P-OD data and arterial geometry. Then, the damping capacity was calculated from these loops with both linear and nonlinear methods. Our results demonstrate that the linear approach provides a reasonable approximation of damping capacity for all of the loops except the Cauchy stress-Almansi strain, for which the estimate of damping capacity was significantly smaller (22 +/- 8% with the nonlinear method and 31 +/- 10% with the linear method). Between healthy and diseased extralobar pulmonary arteries, both methods detected significant differences. However, the estimate of damping capacity provided by the linear method was significantly smaller (27 +/- 11%) than that of the nonlinear method. We conclude that all loops except the Cauchy stress-Almansi strain loop can be used to estimate artery wall damping capacity in the physiological pressure range and the nonlinear method is recommended over the linear method. PMID- 24231966 TI - Mechanical loading causes detectable changes in morphometric measures of trabecular structure in human cancellous bone. AB - The relationships between mechanical loads and bone microstructure are of interest to those who seek to predict bone mechanical properties from microstructure or to predict how organization of bone microstructure is driven by mechanical loads. While strains and displacements in the material are inherently responsible for mechanically caused changes in the appearance of the microstructure, it is the morphometric measures of microstructural organization that are often available for assessment of bone quality. Therefore, an understanding of how strain history is reflected in morphometric measures of bone microstructure has practical implications in that it may provide clinically measurable indices of mechanical history in bone and improve interpretation of bone mechanical properties from microstructural information. The objective of the current study was to examine changes in morphometric measures of cancellous bone microstructure in response to varying levels of continuum level strains. The experimental approach included stereologic analysis of microcomputed tomography (MUCT) images of human cancellous bone samples obtained at sequentially increasing levels of strain in a custom-made loading apparatus mounted in a MUCT scanner. We found that the degree of anisotropy (DA) decreased from baseline to failure and from failure to postfailure. DA partially recovered from postfailure levels upon unloading; however, the final DA was less than at failure and less than at baseline. We also found that average trabecular thickness (Tb.Th.Av) increased with displacements at postfailure and did not recover when unloaded. Average trabecular number decreased when the specimens were unloaded. In addition, the heterogeneity of Tb.Th as measured by intra-specimen standard deviation (Tb.Th.SD) increased and that of trabecular number (Tb.N.SD) decreased with displacements at postfailure. Furthermore, the intraspecimen coefficient of variation of trabecular number decreased at postfailure displacements but did not recover upon unloading. Finally, the coefficient of variation of trabecular separation at unload was less than that at baseline. These measures can be developed into image-based indices to estimate strain history, damage, and residual mechanical properties where direct analysis of stresses and strains, such as through finite element modeling, may not be feasible. It remains to be determined how wide a time interval can be used to estimate strain history before remodeling becomes an overriding effect on the trabecular architecture. PMID- 24231967 TI - Addressing some misperceptions of the joint coordinate system. AB - The joint coordinate system convention proposed by Grood and Suntay has been widely adopted, but often misrepresented. Previous work has argued by logical explanation of the approach that the joint coordinate system is a set of Euler or Cardan angles. The current work offers both an explanation and mathematical proof that the joint coordinate system convention is equivalent to a Cardan angle sequence, thereby demonstrating the joint coordinate system angles are both sequence dependent and orthogonal. PMID- 24231968 TI - Filamentous microbes indigenous to the murine small bowel: A scanning electron microscopic study of their morphology and attachment to the epithelium. AB - Segmented, filamentous prokaryotic microorganisms colonize and attach to the cells in the epithelium of the mucosa of the small bowels of mice and rats. Scanning electron micrographs, derived from specimens of mouse small intestine, reveal microbial filaments of at least two types. One type is thin (0.8MUm) with only faint lines suggesting septa; the other is thicker (1.4MUm) and has distinct segments with pronounced septa. Most of the segments are rounded; a few are thin and elongated. Immediately surrounding the attachment site of these organisms, the surface of the epithelial cells appears roughened and occasionally stringy. The filaments may differ morphologically because they represent different phases in the life cycle of a single microbial type. Alternatively, however, they may differ because they are the cells of different microbial types colonizing the same epithelial habitat. PMID- 24231969 TI - Naturally occurring apatite as a source of orthophosphate for growth of bacteria and algae. AB - Several naturally occurring calcium-phosphate apatites which varied in crystalline structure and ionic composition were added as crystals of different particle size to P-free (<1MUg/liter total P) nutrient media. Sufficient ortho-PO 4 (3-) was released by the partial dissolution of apatite crystals at limnetic pH levels (pH 7.8) to support growth of several unialgal-mixed bacterial cultures. The biomass produced by mixed populations increased as the amount of available apatite was increased and as the pH of the media and the particle size of the apatite crystals were decreased. These findings suggest that although apatite characteristically displays reduced solubility under alkaline conditions, the tons of apatite which are continuously entering aquatic environments as erosion material may be contributing to the P loading of those ecosystems. PMID- 24231970 TI - Influence of extracellular polysaccharides on the toxicity of copper and cadmium towardKlebsiella aerogenes. PMID- 24231971 TI - A case for bacterial dormancy in aquatic systems. PMID- 24231972 TI - The annual cycle ofVibrio Parahaemolyticus in chesapeake bay. AB - An ecological study ofVibrio parahaemolyticus was carried out from December 1970 to December 1971 in the Rhode River of Chesapeake Bay. The annual cycle of the organism was elucidated and factors restricting its distribution in the estuary were described, including the association of the organism with zooplankton. Numerical taxonomy was employed for identification and classification ofV. parahaemolyticus and related organisms on the basis of substrate utilization tests. From characteristics recorded forV. parahaemolyticus, it is concluded to be an estuarine organism. PMID- 24231973 TI - Nematophagous fungi: Endoparasites ofRhabditis terricola. AB - Three techniques were compared for the recovery of endoparasitic nematophagous fungi from soil. The Baermann funnel technique (32 species) was superior to differential centrifugation (19 species) or soil sprinkling (21 species) in terms of number of species found. The main advantage of the Baermann funnel was in the recovery of lower fungi, especially those with flagellate states. In all, 40 species of endoparasites (70% of the known flora) were recorded. Thirty-two of those were found capable of attacking the soil nematodeRhabditis terricola Dujardin. PMID- 24231974 TI - Bacterial chemotactic responses in flowing water. AB - Chemotaxis in marine bacteria is shown to be the basis for instream location in flowing water. The response is of importance in the location of prey by motile bacterial predators. PMID- 24231975 TI - Predictive and postdictive success of statistical analyses of yield trials. AB - The accuracy of a yield trial can be increased by improved experimental techniques, more replicates, or more efficient statistical analyses. The third option involves nominal fixed costs, and is therefore very attractive. The statistical analysis recommended here combines the Additive main effects and multiplicative interaction (AMMI) model with a predictive assessment of accuracy. AMMI begins with the usual analysis of variance (ANOVA) to compute genotype and environment additive effects. It then applies principal components analysis (PCA) to analyze non-additive interaction effects. Tests with a New York soybean yield trial show that the predictive accuracy of AMMI with only two replicates is equal to the predictive accuracy of means based on five replicates. The effectiveness of AMMI increases with the size of the yield trial and with the noisiness of the data. Statistical analysis of yield trials with the AMMI model has a number of promising implications for agronomy and plant breeding research programs. PMID- 24231976 TI - Mutants for rice storage proteins : 1. Screening of mutants for rice storage proteins of protein bodies in the starchy endosperm. AB - To obtain genetic materials to breed qualitatively improved rice storage proteins, we screened about 3,000 mutant lines induced by the treatment of rice fertilized egg cell with N-methyl-N-nitrosourea (MNU). The screening was performed by comparing the profiles of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with that of the original variety, Kinmaze, especially focussing on the changes in polypeptides present in two kinds of protein bodies, PB-I and PB-II. We selected 17 mutant lines and classified them into 4 types on the basis of variations of the relative contents of the polypeptides. Determination of extracted protein in the starchy endosperm of the mutants revealed changes in the content of prolamin and glutelin but not globulin. In some mutants there was marked accumulation of 57 kDa polypeptide concomitant with the remarkable reduction of glutelin subunits. Treatment of the fertilized egg cell with MNU was found to be an effective method to induce mutations for storage proteins in protein bodies of rice. PMID- 24231977 TI - The emergence of new centres of diversity: evidence from barley. AB - Statistical analyses of data from a large barley germplasm collection of worldwide origins revealed that material from the USA now contains more variability in toto than material from any other country. In addition trends of overall diversity for other countries suggest that there is little association between high overall variability and what are considered as traditional "centres of origin" or "centres of diversity" for this crop. The five countries of highest overall diversity worldwide were found to be (in descending order): USA, Turkey, Japan, USSR and China. Cluster analyses revealed that relatedness of germplasm was by far strongest between certain European countries, which were also in general of a more intermediate diversity level. The data presented here suggests that the variability present in gene pools still varies substantially by country but according to patterns which appear different from those described previously. PMID- 24231978 TI - Mitochondrial DNA variation in pearl millet and related species. AB - Mitochondrial DNA (mtDNA) restriction endonuclease fragment patterns and patterns of mtDNA hybridized by mitochondrial gene probes were used to study phylogenetic relationships of seven Pennisetum species, including five P. americanum (pearl millet) ecotypes and a reference species from the distantly related genus, Panicum. The restriction patterns of the pearl millet ecotypes were uniform with the exception of the ecotype collected in Ethiopia. The probe hybridization method revealed more variability, with both the Rhodesian and Ethiopian ecotypes differing from the others and from each other. Considerable restriction pattern polymorphism was noted among different species of Pennisetum, and Panicum. Significant relationships were noted of Pennisetum polystachyon to P. pedicellatum and of P. purpureum to P. squamulatum using the restriction pattern method. In addition to those relationships, the hybridization method showed relationships of pearl millet to P. purpureum and to P. squamulatum. The relationships noted between species by the hybridization method agreed more closely to the cytological data than those indicated by the restriction pattern method. Therefore, the hybridization method appeared to be the preferred method for studying species relationships. The mitochondrial genome size of pearl millet was calculated to be 407 kb and the mitochondrial genome sizes of other Pennisetum species ranged from 341 to 486 kb. PMID- 24231979 TI - The use of cross prediction methods in a practical potato breeding programme. AB - Most previous studies on cross prediction methods have examined relatively few crosses, particularly in relation to the numbers involved in most breeding programmes. In this paper the feasibility of using cross prediction methods was examined in a practical potato (Solanum tuberosum) breeding scheme by the analyses of progeny from 52 crosses. The variate considered was breeder's preference, a visual assessment made of the harvested tubers to estimate their commercial potential. The results showed that it was possible to identify the superior crosses. Cross prediction based simply on the mean preference scores, averaged over scorers and clones within progenies, estimated on seedlings or first clonal year plants, provided the best estimate of a progeny's performance in the third clonal generation. Predictions based on the expected proportion of clones that would transgress a given target value also provided a good indication of a progeny's potential. The poorest prediction was obtained by using the observed frequency of desirable clones in a progeny sample. The implications for potato breeding are discussed. PMID- 24231980 TI - Associations among inbred lines of maize using electrophoretic, chromatographic, and pedigree data : 2. Multivariate and cluster analysis of data from Iowa stiff stalk synthetic derived lines. AB - Associations among 17 "Iowa Stiff Stalk Synthetic" derived inbred lines of maize (Zea mays L.) were determined using multivariate and cluster analysis. Objectives were to assess the level of unique characterization among lines afforded by reversed-phase high-performance liquid chromatography (RP-HPLC) of zeins and starch gel electrophoresis of isozymes and to compare associations among lines revealed by biochemical and pedigree data. Isozymic data for 33 loci provided unique discrimination among 88% of the lines; 2 closely related lines were indistinguishable. Seventy-one percent of the lines could be uniquely and unambiguously identified by RP-HPLC. Biochemical data showed associations between lines that would be expected on the basis of pedigree. Nevertheless, different associations were revealed by allozymic and chromatographic data. Although these data permitted a high degree of unique identification, additional markers, covering a larger proportion of the genome, are needed to more adequately monitor similarities among genes that respond to selection during plant breeding. PMID- 24231981 TI - Heterochromatins and band karyotypes in three species of salmonids. AB - The heterochromatins of rainbow trout (Salmo gairdneri R.), brown trout (Salmo trutta fario L.) and brook trout (Salvelinus fontinalis M.) were characterized by sequential chromomycin A3/distamycin A/DAPI (CDD) and DAPI/actinomycin D (DAPI/AmD) fluorescence. On most biarmed chromosomes, an equilocal localization of prominent DAPI/AmD positive, chromomycin A3 negative, AT-rich blocks at the centromeres were observed in all three species. Band karyotypes of the three species were established. In rainbow trout, several DAPI/AmD positive heterochromatin blocks behaved positive in a silver-staining method. Mitotic and interphase studies proved the presence of inter-individual NOR variation in brown trout. The NORs of brook trout were localized on chromosomes 5, 10, 14, 15 and 29. PMID- 24231982 TI - Inheritance of supernodulation in soybean and estimation of the genetically effective cell number. AB - Provided the nature of inheritance is known, the frequency of homozygous mutant plants in individual M2 families (derived from M1 seed) can be used to estimate the genetically effective cell number (GECN). Segregation ratios in M3 families derived from M2 wild-type plants indicated that the supernodulation characters nts382, nts1007 and nts183 are inherited as Mendelian recessives. The nature of inheritance was also known or confirmed to be recessive by crossing the wild type to these and several other mutants derived from the same population of M2 families. Subsequently, using the frequency of mutant plants in individual M2 families, the GECN for soybean was calculated to be approximately two. PMID- 24231983 TI - Large double-stranded RNA molecules in Phaseolus vulgaris L. are not associated with cytoplasmic male sterility. AB - Two large double-stranded RNA molecules, 15 and 16 kilobases, were detected in cytoplasmic male sterile (CMS) Phaseolus vulgaris by agarose gel electrophoresis. A number of smaller RNA molecules were observed in 'Sprite', a maintainer line, and recurrent backcrossing of CMS P. vulgarisx'Sprite' resulted in a combined electrophoretic pattern of the two large and numerous small RNA molecules. The large RNA molecules were seed and pollen-transmissible, but were not transmitted by grafting. The RNAs were present in revertant and restored lines derived from CMS-Sprite and therefore were not associated with the cytoplasmic male sterile trait. PMID- 24231984 TI - On the toleration of duplications and deletions by the Vicia faba genome. AB - From eight pairs of crosses between differently reconstructed diploid karyotypes of Vicia faba, the progeny after selfing of plants heterozygous for both parental chromosome reconstructions were inspected for occurrence and transmission of duplications and deletions of defined chromosome segments, comprising together about one third of the metaphase genome length. The duplications and deletions studied involved either one or more chromosome segments of the respective karyotype (0.8%-9.1% of the metaphase length). They arose during meiosis in double heterozygotes by crossing over between partially homologous chromosomes or by mis-segregation from multivalents. While most duplications, provided they were not accompanied by deletions and in dependence on the segment involved, were viable and transmissible, even in homozygous state, deletions had lethal effects on gametes of both sexes. PMID- 24231985 TI - A mutant of Nicotiana sylvestris deficient in serine glyoxylate aminotransferase activity : Callus induction and photorespiratory toxicity in regenerated plants. AB - A photorespiration mutant of Nicotiana sylvestris lacking serine: glyoxylate aminotransferase activity was isolated in the M2 generation following EMS mutagenesis. Mutants showing chlorosis in air and normal growth in 1% CO2 were fed [(14)C]-2-glycolate to examine the distribution of (14)C among photorespiratory intermediates. Mutant strain NS 349 displayed a 9-fold increase in serine accumulation relative to wild-type controls. Enzyme assays revealed an absence of serine: glyoxylate aminotransferase (SGAT) activity in NS 349, whereas other peroxisomal enzymes were recovered at normal levels. Heterozygous siblings of NS 349 segregating air-sensitive M3 progeny in a 3?1 ratio were shown to contain one half the normal level of SGAT activity, indicating that air sensitivity in NS 349 results from a single nuclear recessive mutation eliminating SGAT activity. Since toxicity of the mutation depends on photorespiratory activity, callus cultures of the mutant were initiated and maintained under conditions suppressing the formation of functional plastids. Plantlets regenerated from mutant callus were shown to retain the SGAT deficiency and conditional lethality in air. The utility of photorespiration mutants of tobacco as vehicles for genetic manipulation of ribulose bisphosphate carboxylase/oxygenase at the somatic cell level is discussed. PMID- 24231986 TI - An alternative approach to multivariate selection in plant breeding where genotypes are evaluated at many locations. AB - A new approach to genotypic selection in a plant breeding programme where the genotypes under assessment are grown in a number of environments is examined. It is assumed that these environments are a random sub-set of all possible environments where the genotypes are likely to be grown. It involves estimating the probability that each genotype will, if grown at any location, exceed predefined target values for one or more characters. The multi-normal probabilities are estimated from the genotype means and environmental variance of each variate. Where more than a single variate is to be considered, the correlation coefficients between variates are also used in the estimation. It was found that the coefficient obtain by correlating the predicted proportion of locations that genotypes would exceed the set target values, with the observed proportion of locations in a different year, were consistently higher than similar coefficients between observed proportions in different seasons. The latter were high enough to conclude that the approach would be of use in practise. Such a method may therefore be used to identify genotypes which have a high probability of being suitable over a range of locations. PMID- 24231987 TI - Genetic evaluation with data presenting evidence of mixed major gene and polygenic inheritance. AB - A procedure for genetic evaluation with field data is proposed for situations in which there is mixed major gene and polygenic inheritance and the major genotype membership of some or of all individuals is unknown. Location parameters (fixed environmental, major genotype and polygenic effects), major genotype frequencies and variance components are estimated by the modal values of joint and marginal posterior distributions. The method is described for continuous and discontinuous data as well as for univariate and multivariate evaluations. Results from a simulation study are presented. PMID- 24231988 TI - The cytogenetics of a triploid Hordeum bulbosum and of some of its hybrid and trisomic derivatives. AB - The progeny from a cross between diploid H. vulgare and triploid H. bulbosum were mostly triploid (VBB) hybrids, the other progeny were haploid (V) barley (H. vulgare). From a cross between diploid and triploid H. bulbosum, four of the seven possible trisomic lines were isolated. The Giemsa banded karyotype of H. bulbosum was produced, and two of the lines were identified as trisomic for chromosomes 6 and 7. The cytology and transmission rates of the trisomics were examined. PMID- 24231989 TI - Variation in kafirin and alcohol-soluble glutelin chromatograms of sorghum inbred lines revealed by reversed-phase high-performance liquid chromatography. AB - Separations of kafirin and alcohol soluble glutelin proteins by reversed-phase high-performance liquid chromatography (RP-HPLC) from 7 inbreds and one hybrid of sorghum [Sorghum bicolor (L.) Moench] and one source of Johnsongrass [Sorghum halapense (L.) Pers.] were compared. Objectives were to assess the stability of protein profiles for seed sources produced at different locations and in different environments to examine the potential of RP-HPLC to provide genotypic profiles for sorghum. Analyses of variance data showed that levels of variation due to environments and locations were small; the majority of variation (93%) was among genotypes. Associations among inbreds revealed by multivariate and cluster analysis showed similarity with those that would be expected on the basis of pedigree. A chi-square analysis showed no deviation in the hybrid profile from the expected 2?1 ratio of peaks from the female and male inbred parents, respectively. Improvements in the ability to correctly assign common peaks are necessary before associations among numerous sorghum genotypes can be reliably demonstrated by analysis of data from reversed-phase high-performance liquid chromatography (RP-HPLC). PMID- 24231990 TI - Novel class of rDNA repeat units in somatic hybrids between Nicotiana and Atropa. AB - Behavior of ribosomal RNA genes in the process of somatic hybridization was analyzed using hybrids Nicotiana tabacum + Atropa belladonna. Blothybridization of parental species DNAs to (32)P-rDNA specific probes revealed two classes of ribosomal repeats in both tobacco and nightshade; their length was 11.2 kb, 10.4 kb (tobacco) and 9.4 kb, 10.2 kb (night-shade). For analysis of hybrids, labelled (32)P rDNA specific probes were hybridized to DNA of parental species and somatic hybrids digested with restriction endonucleases EcoR1, EcoRV and BamH1. A new class of ribosomal DNA repeat, absent in parental species, was found in hybrid line NtAb-1. Possible mechanisms of appearence of a new rDNA class in the process of somatic cell fusion are discussed. PMID- 24231991 TI - Resistance to potato leaf roll virus and potato virus Y in somatic hybrids between dihaploid Solanum tuberosum and S. brevidens. AB - Many somatic fusion hybrids have been produced between a dihaploid potato Solanum tuberosum and the sexually-incompatible wild species S. brevidens using both chemical and electrical fusion techniques. S. brevidens was resistant to both potato leaf roll virus (PLRV) and potato virus Y (PVY), the viruses being either at low (PLRV) or undetectable (PVY) concentrations as determined by enzyme-linked immunosorbent assay (ELISA). The S. tuberosum parent was susceptible to both viruses. A wide range of resistance, expressed as a decrease in virus concentration to both viruses was found amongst fusion hybrids, four of which were especially resistant. The practicality of introducing virus resistance from S. brevidens into cultivated potatoes by somatic hybridisation is discussed. PMID- 24231992 TI - Chromosome elimination and chromosome pairing in tetraploid hybrids of Hordeum vulgare * H. bulbosum. AB - The C0 tetraploid counterparts of diploid hybrids of Hordeum vulgare * H. bulbosum were meiotically analysed, and were found to be chromosomally less stable than the same genotypes had been as diploids. The 14 bulbosum chromosomes present in the tetraploid cytotypes were probably eliminated as pairs rather than randomly or one genome at the time. Development of the vulgare and bulbosum genomes was asynchronous in some hybrids, the bulbosum chromosomes appearing less advanced than the vulgare chromosomes in the same cell. This appeared to reduce pairing between bulbosum homologues and also suppressed homoeologous pairing. PMID- 24231993 TI - The detection and estimation of linkage using doubled haploid or single seed descent populations. AB - In many plant species, particularly those of agricultural importance, there is now much effort being devoted to developing comprehensive genetic maps using biochemical and molecular markers. Because these techniques often involve destructive sampling of individual plants the use is increasingly made of homozygous or near-homozygous recombinant lines for linkage studies in preference to F2 or backcross generations. The present paper describes methods for the detection and estimation of linkage using such generations for commonly encountered genetic situations. PMID- 24231994 TI - Transfer of resistance to PLRV titer buildup from Solanum etuberosum to a tuber bearing Solanum gene pool. AB - Hybrids between Solanum etuberosum and S. pinnatisectum harboring resistance to titer buildup of potato leafroll virus (PLRV) were reciprocally crossed with tuber-bearing wild species S. acaule and S. verrucosum. A total of 47 hybrids with acaule were obtained with the aid of embryo rescue and sterile culturing of embryos from imbibing seeds. All but two hybrids with acaule had low pollen stainabilities or were pollen sterile. Hybrid seeds from crosses with verrucosum were easily obtained, and the triploid progenies were sterile. Hybrid progeny were screened for resistance to PLRV infection by viruliferous green peach aphid and for resistance to titer buildup. Although hybrids did not exhibit resistance to infection, PLRV was not detectable using ELISA. Virus was detected, however, by graft transmission to Datura stramonium. Crosses of fertile acaule-etuberosum pinnatisectum hybrids with S. phureja, a cultivated diploid, using the latter as pollen parent, produced berries but seed did not complete development and was aborted. Rescue of immature embryos 25 days after pollination by excision from berries and sterile culture produced vigorous, pot-cultured plants. Segregation of susceptible (virus detected) and resistant (virus undetected) progenies suggests simple inheritance. PMID- 24231995 TI - Heterosis * nutrition interaction in Drosophila melanogaster. AB - The relationship between heterozygosity and the expression of heterosis at two different nutrition levels was investigated using Drosophila melanogaster. Average daily egg production and egg hatchability were measured in two parental strains and in F1, F2 and reciprocal backcross generations. Heterosis was more pronounced in the poor nutritional conditions. Two electrophoretic markers used to estimate the level of heterozygosity in F2 and backcrosses revealed an excess of heterozygous genotypes. Quantitative genetic effects (an additive line effect and individual and maternal heterosis) were estimated for both traits in the two environments. Although this model gave a reasonable fit in most cases, some epistatic interaction would have to be invoked in order to explain fully the results. PMID- 24231996 TI - Soybean 11S globulin polypeptides have an antigenic homology with 11S globulins from various plants. AB - Rabbit serum antibodies (AB) against glycinin acidic polypeptides were separated by cross exhausting, and the antibody fractions for each of the two subfamilies of glycinin subunits (A1 and A3) were obtained. The antibodies were used in the immuno blot assay with seed protein of various plant classes. Polypeptides homologous to soybean glycinin were detected. Homology with A1 polypeptide was revealed in more cases than with A3. Total seed protein preparations were subjected to centrifugation in sucrose density gradient, and the polypeptides, imunochemically related to glycinin, occurred only in fractions with sedimentation constant about 11S. The nativity of conservative antigenic determinants of 11S globulins is discussed. PMID- 24231997 TI - Phenotypic and genetic variability of estimated growth curve parameters in mice. AB - Data from 1,919 outbred ICR mice were used to examine the potential usefulness of growth curve parameters as selection criteria for altering the relationship between body weight and age. A logistic growth function was used to model growth through 12 weeks of age. Estimates of asymptotic weight (A), maximum growth rate (r) and age at point of inflection (t(*)) were obtained by nonlinear least squares. A log transformation was also used to stabilize residual variance. Phenotypic and genetic parameters were estimated for the estimated growth curve parameters and for body weights at 2, 3, 4.5, 6, 8 and 12 weeks of age. Heritabilities of estimated growth curve parameters (obtained with and without a log transformation, respectively) were: A (0.28+/-0.07, 0.28+/-0.07), r (0.35+/ 0.07, 0.53+/-0.09) and t(*) (0.41+/-0.08, 0.44+/-0.08). Estimated genetic correlations suggest that t(*) may be useful in selecting for rapid early growth without increasing mature weight. PMID- 24231998 TI - Selection for increased anther culture response in maize. AB - Anther culture of a three-way cross, (H99 * FR16) * Pa91, resulted in the regeneration of two anther-derived plants which were crossed to produce an F1 progeny. Fourteen S1 families derived from this cross were evaluated for their anther culturability. Dramatic increases in the level of androgenesis, expressed as the percentage of cultured anthers which produced embryo-like structures, were observed. An overall mean response frequency of 23.4% was observed for the S1 families. This was compared to a 3.5% response in the original three-way cross. These results demonstrate that genetic improvement of in vitro androgenesis in maize is possible and that anther culture per se constitutes a procedure for selecting genes which favor increased levels of response. PMID- 24231999 TI - Release of tissue inhibitor of metalloproteinase-2 from alginate microcapsule encapsulating genetically engineered cells. AB - BACKGROUND: In this study, 293T cells were genetically engineered to secrete tissue inhibitor of metalloproteinase-2 (TIMP2) and encapsulated into alginate microcapsules to continuously release TIMP2 protein. METHODS: The anti-invasive potential of the microcapsules was studied in vitro using brain tumor cells. The TIMP2 gene was transfected to 293T cells, and genetically engineered 293TIMP2 cells were encapsulated into alginate microcapsules. Release of TIMP2 protein was detected with Western blot analysis and the anti-invasive potential against U87MG cells was tested using gelatin zymography and a Matrigel assay. RESULTS: Cell viability within the alginate microcapsules was maintained at a cell density of 5 * 10(6). Because polycationic polymers are helpful for maintaining the mechanical strength of microcapsules with good cell viability, the alginate microcapsules were reinforced with chitosan (0.1% w/v). Expression of TIMP2 protein in cell lysates and secretion of TIMP2 into the conditioned medium was confirmed by Western blot analysis. Alginate microcapsules encapsulating 293TIMP2 cells released TIMP2 protein into the medium efficiently, where the TIMP2 protein participated in degradation of the matrix metalloproteinase-2 enzyme and inhibited invasion of U87MG cells. CONCLUSION: Alginate microcapsules encapsulating 293TIMP2 cells are promising candidates for anti-invasive treatment of glioma. PMID- 24232000 TI - Protective effects of Notoginsenoside R1 on intestinal ischemia-reperfusion injury in rats. AB - Intestinal ischemia and reperfusion (I/R) is a clinical problem occurred for diverse causes with high mortality. Prophylaxis and treatment of intestinal I/R remains a challenge for clinicians. The purpose of the present study was to explore the role of Notoginsenoside R1 (R1), a major component form of Panax notoginseng, in management of intestinal I/R injury. Intestinal I/R was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 90 min followed by reperfusion for 60 min or 3 days. R1 (10 mg.kg(-1).h(-1)) was administered either 20 min before ischemia or 20 min after reperfusion. Intestinal microcirculation was evaluated by intravital microscopy over 60 min reperfusion. Sixty minutes or 3 days after reperfusion, rats were killed for histological examination of the jejunum tissue and immunohistochemical localization of myeloperoxidase and CD68. ATP, ADP, and AMP content in jejunum tissue was assessed by ELISA. Activation of nuclear factor-kappaB (NF-kappaB) and expression of ATP5D and tight junction proteins were determined by Western blotting. The results demonstrated that R1 is capable of attenuating intestinal I/R-induced microvascular hyperpermeability, inflammatory cytokine production, NF kappaB activation, and loss of tight junction proteins, as well as improving energy metabolism during I/R. The results of the present study suggest R1 as an option in protecting against intestinal I/R injury. PMID- 24232001 TI - Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway. AB - Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS) induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-alpha and IL-6, and the mRNA expression of proinflammatory mediators (MCP-1, Cox2, IFN-gamma, TNF-alpha, IL-6, and IL-17). The decline in the activation of NF-kappaB p65, ERK, JNK, and p38 MAPK correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) but not TLR2 or TLR5 expression. In accordance with the in vivo results, paeoniflorin downregulated TLR4 expression, blocked nuclear translocation of NF-kappaB p65, and reduced the production of IL-6 in LPS-stimulated mouse macrophage RAW264.7 cells. Transient transfection assay performed in LPS-stimulated human colon cancer HT-29 cells indicated that paeoniflorin inhibits NF-kappaB transcriptional activity in a dose dependent manner. TLR4 knockdown and overexpression experiments demonstrated a requirement for TLR4 in paeoniflorin-mediated downregulation of inflammatory cytokines. Thus, for the first time, the present study indicates that paeoniflorin abrogates DSS-induced colitis via decreasing the expression of TLR4 and suppressing the activation of NF-kappaB and MAPK pathways. PMID- 24232002 TI - Endothelial nitric oxide synthase uncoupling and microvascular dysfunction in the mesentery of mice deficient in alpha-galactosidase A. AB - A defect in the gene for the lysosomal enzyme alpha-galactosidase A (Gla) results in globotriaosylceramide (Gb3) accumulation in Fabry disease and leads to premature death from cardiac and cerebrovascular events. However, gastrointestinal symptoms are often first observed during childhood in these patients and are not well understood. In this study, we demonstrate an age dependent microvasculopathy of the mesenteric artery (MA) in a murine model of Fabry disease (Gla-knockout mice) resulting from dysregulation of the vascular homeostatic enzyme endothelial nitric oxide synthase (eNOS). The progressive accumulation of Gb3 in the MA was confirmed by thin-layer chromatographic analysis. A total absence of endothelium-dependent dilation was observed in MAs from mice at 8 mo of age, while suppression of ACh-mediated vasodilation was evident from 2 mo of age. Endothelium-independent dilation with sodium nitroprusside was normal compared with age-matched wild-type mice. The microvascular defect in MAs from Fabry mice was endothelium-dependent and associated with suppression of the active homodimer of eNOS. Phosphorylation of eNOS at the major activation site (Ser(1179)) was significantly downregulated, while phosphorylation at the major inhibitory site (Thr(495)) was remarkably enhanced in MAs from aged Fabry mice. These profound alterations in eNOS bioavailability at 8 mo of age were observed in parallel with high levels of 3 nitrotyrosine, suggesting increased reactive oxygen species along with eNOS uncoupling in this vascular bed. Overall, the mesenteric microvessels in the setting of Fabry disease were observed to have an early and profound endothelial dysfunction associated with elevated reactive nitrogen species and decreased nitric oxide bioavailability. PMID- 24232004 TI - No name--no blame. PMID- 24232003 TI - Functional recovery after facial nerve cable grafting in a rodent model. AB - IMPORTANCE: Cable grafting is widely considered to be the preferred alternative to primary repair of the injured facial nerve; however, quantitative comparison of the 2 techniques has not been previously undertaken in a rodent model. OBJECTIVE: To establish functional recovery parameters after interposition autografting in a rodent facial nerve model. DESIGN, SETTING, AND PARTICIPANTS: Prospective randomized animal study at a tertiary care facial nerve center using 16 female Wistar Hannover rats. INTERVENTION: The experimental group received reversed autograft reconstruction of a 20-mm neural gap, and the control group received facial nerve transection and primary repair. MAIN OUTCOME AND MEASURE: Whisker excursion was measured weekly for 70 postoperative days using laser micrometers. RESULTS: The control group exhibited the most rapid recovery, with substantial return of whisker movement occurring during the third postoperative week. The experimental group demonstrated return of function beginning in the fourth postoperative week, eventually achieving a degree of function comparable to that of the control group by the sixth postoperative week (P = .68). CONCLUSIONS AND RELEVANCE: Recovery of facial function after cable grafting seems to be slower than, but eventually similar to, recovery after primary neurorrhaphy in a rodent model. In the present study we have established a benchmark for recovery of whisker movement across a 20-mm rodent facial nerve gap, which will be used for comparison of different facial nerve gap bridging materials in future studies. LEVEL OF EVIDENCE: NA. PMID- 24232005 TI - Neck pain and swelling in a young man. PMID- 24232006 TI - BET 1: Levosimendan in cardiogenic shock secondary to acute myocardial infarction. AB - A short-cut review was carried out to establish whether levosimendan improves outcome in cases of cardiogenic shock. Five studies were directly relevant to the question. One very general systematic review and meta-analysis is also included. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are shown in table 1. The clinical bottom line is that there is no evidence that levosimendan improves outcome in cardiogenic shock. PMID- 24232008 TI - BET 2: leeches (hirudotherapy) or steroids for traumatic obstructive tongue swelling? AB - A short-cut review was carried out to establish whether leeches or steroids are more effective at reducing the size of a tongue haematoma. No studies were directly relevant to the question. Several reviews and case reports were found to suggest that leeches might be effective. The clinical bottom line is that leeches should be considered in the management of obstructive traumatic tongue swelling. PMID- 24232009 TI - BET 3: evaluation of intra-aortic balloon support in cardiogenic shock. AB - A short-cut review was carried out to establish whether intra-aortic balloon pumps (IABP) improve mortality in cardiogenic shock after acute myocardial infarction (AMI). Two studies and one systematic review were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are shown in table 3. The clinical bottom line is that the IABP does not improve mortality in cardiogenic shock after AMI when percutaneous coronary intervention is available. When only thrombolysis is possible then it may improve mortality. PMID- 24232010 TI - Minimal patient handling: a faculty of prehospital care consensus statement. AB - This paper outlines the emerging best practice when packaging a prehospital trauma patient while providing spinal immobilisation. The best practice described is based on the recommendations of a consensus meeting held by the Faculty of Pre Hospital Care, Royal College of Surgeons of Edinburgh, in the West Midlands in April 2012, where the opinion of experienced practitioners from across the prehospital and emergency care community considered the currently available evidence and reviewed current clinical practice. Initial consensus points were then subject to further review and dialogue with stakeholders from the initial meeting. The recommendations drawn from the meeting and subsequent dialogue represent a 'general agreement' to the principles and practices described in the paper. The recommendations will provide guidance for clinical practice and governance alongside other consensus statements from the Faculty of Pre-Hospital Care that seek to address prehospital spinal immobilisation and pelvic immobilisation. PMID- 24232011 TI - Pre-hospital spinal immobilisation: an initial consensus statement. AB - This paper reviews the current evidence available on the practice of spinal immobilisation in the prehospital environment. Following this, initial conclusions from a consensus meeting held by the Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh in March 2012 are presented. PMID- 24232012 TI - The prehospital management of pelvic fractures: initial consensus statement. PMID- 24232013 TI - Pharmacologically assisted laryngeal mask insertion: a consensus statement. PMID- 24232015 TI - Neutral polyfluoroalkyl substances in the global atmosphere. AB - Concentrations of neutral per- and polyfluoroalkyl substances (nPFAS) in the atmosphere are of interest because nPFAS are highly mobile percursors for perfluoroalkyl acids. Two calibration studies in Ontario, Canada and Costa Rica established the feasibility of using XAD 2-resin based passive air samplers (XAD PAS) to reliably determine long term average air concentrations of nPFAS under temperate and tropical climatic conditions. The temporal and spatial distribution of nPFAS was investigated by analyzing XAD-PAS deployed for one year at between 17 and 46 sites on six continents between 2006 and 2011 as part of the Global Atmospheric Passive Sampling (GAPS) study. Higher levels of fluorotelomer alcohols (FTOHs) compared to fluorinated sulfonamides (FOSAs), and fluorinated sulfonamidoethanols (FOSEs) were observed at all sites. Urban sites had the highest levels of nPFAS compared to rural and remote sites, which is also apparent in a positive correlation of nPFAS levels with the proximity of a sampling site to areas of high population density. Levels of FOSAs and FOSEs tended to decrease during the six years of measurements, whereas an initial decline in the concentrations of FTOHs from 2006 to 2008 did not continue in 2009 to 2011. A comparison of nPFAS levels measured in national XAD-PAS networks in Costa Rica and Botswana revealed that the GAPS sites in Tapanti and the Kalahari are representative of the more remote regions in those countries. XAD-PAS derived absolute nPFAS levels at GAPS sites are lower than those measured using another PAS, but are within the range of levels measured with active air samplers. Agreement of relative nPFAS composition is better between samplers, suggesting that the discrepancy is due to uncertain sampling rates. PMID- 24232016 TI - Identification of tonoplast and plasma membrane in membrane fractions from garden cress (Lepidium sativum L.) with and without filipin treatment. AB - Membranes from roots of Lepidium sativum L. were investigated in situ and after fractionation by applying morphological and biochemical methods. After freeze fracture combined with filipin labelling the tonoplast and the plasma membrane could be easily characterized by the frequency of intramembranous particles and the arrangement of filipin-induced lesions. On tonoplast vesicles, the filipin induced lesions were arranged in clusters of different size whereas they were evenly distributed on plasma membrane vesicles. Enrichment of tonoplast and plasma membrane in different fractions was documented by filipin labelling, phosphotungstic acid staining and by the profiles of marker enzyme activities and ATP-dependent H(+)-transport. Additionally, the presence of rightside-out and inside-out vesicles of both tonoplast and plasma membrane could be demonstrated. It was found that filipin labelling used in combination with freeze-fracturing is suitable for quantitative determinations of the percentages of tonoplast and plasma membrane in membrane fractions, which have been found to be more than 40% for the tonoplast and about 40% for plasma membrane in the respective enriched fractions. PMID- 24232017 TI - Purification of plastids from higher-plant roots. AB - A procedure is described for the purification of plastids from the roots of Pisum sativum L. The preparations obtained are appreciably free of contamination by other particles as judged by the distribution of organelle-specific marker enzymes and by electron microscopy. Latency of glutamate synthase (EC 2.6.1.53) within these preparations indicates that the plastids obtained are 90-95% intact, whilst the resistance of this enzyme, and glucose-6-phosphogluconate dehydrogenase (EC 1.1.1.43) to tryptic digestion in unlysed organelles indicates that they are at least 70-85% intact and may be suitable for studies of metabolite transport. PMID- 24232018 TI - Chromoplasts of Palisota barteri, and the molecular structure of chromoplast tubules. AB - Ripe, deep-red fruits of Palisota barteri contain tubulous chromoplasts which develop from unpigmented leucoplasts. These plastids contain, besides large spherical inclusion bodies, numerous osmiophilic globules which, in the course of ripening, frequently show transition states to tubular structures. The tubules contain, in all stages of their development, acylated beta-citraurin, which is also the main pigment of Citrus fruits. The tubular structures have been isolated, fragmented by French-pressure treatment, and separated into three fractions on sucrose gradients. The lightest fraction (1.044 g.cm(-3)) contained thick fragments ('saccules') with diameters of 50-60 nm, whereas the heaviest (1.083 g.cm(-3)) consisted of tubules 20-25 nm in diameter. The relative amounts of polar lipids, proteins, and carotenoids of the different fractions are consistent with a molecular structure model of tubules and saccules, according to which a wick of longitudinally oriented carotenoid molecules of variable thickness is coated by a monolayer of polar lipids and proteins. High-resolution 'negative-stainings' showed the surface of the tubules to be covered with globular particles of about 6 nm diameter. The main protein of all fractions is a 30-kDa polypeptide; it is assumed that the particles are oligomers of this specific protein. PMID- 24232019 TI - Chloroplast and extrachloroplastic starch-degrading enzymes in Pisum sativum L. AB - Starch-degrading enzymes in isolated pea (Pisum sativum L. cv. Laxton's Progress No. 9) chloroplasts were investigated and compared with those in crude pea leaf and stipule preparations. End-product analysis of amylopectin degradation by chloroplast and crude extracts indicates that maltose is the major product of both. Two multiforms of beta-amylase (EC 3.2.1.2) were detected in pea chloroplasts using an electrophoretic transfer technique. A starch-debranching enzyme (EC 3.2.1.10) was detected in chloroplasts by electrophoretic transfer and the degradation of pullulan. A different multiform of debranching enzyme was found in crude preparations. alpha-Amylases (EC 3.2.1.1) were detected by electrophoretic transfer through gels containing starch and starch azure, and by change in viscosity of a starch solution, but were only found in crude preparations indicating an extrachloroplastic location. Incubation of maltotriose with chloroplast extracts gave high levels of glucose production and formation of oligosaccharides with degrees of polymerization larger than that of maltotriose indicating transglycosylase (EC 2.4.1.25) activity. Neither alpha-glucosidase (EC 3.2.1.20) nor maltose-phosphorylase (EC 2.4.1.1) activity were found in either chloroplast or crude preparations, whereas starch-phosphorylase (EC 2.4.1.1) activity was in both. The possible role of these enzymes in starch degradation by pea chloroplasts is discussed. PMID- 24232020 TI - Analysis of growth components in Allium roots. AB - Root growth was analyzed in Allium cepa L. grown under steady-state conditions at 10, 15 and 25 degrees C by measuring cell sizes along the meristem and mature zones at these three temperatures and in the elongation zone at 15 degrees C. The absolute rate of growth, v(x), was determined as a function of the mean cell number of cells entering a point x of the root axis and their mean length. Likewise, the relative elemental rate of root growth, g(x), and its components, namely, the relative elemental rate of cell formation, r(x), and the relative elemental rate of cell elongation, e(x), were determined, where g(x)=r(x)+e(x). A fine analysis of quantitative and topographical features of cell division and cell enlargement was carried out along the root axis. Finally, a simple hypothesis is proposed for the control of cell growth and cell division by the interaction with the cell mass of two regulatory, signal factors (proliferative and growth), distributed in opposite gradients along the root axis, between the quiescent centre and the mature zone. PMID- 24232021 TI - Metabolism of gibberellins in a cell-free system from immature seeds of Phaseolus vulgaris L. AB - The biosynthetic steps from gibberellin A12-aldehyde (GA12-aldehyde) to C19-GAs were studied by means of a cell-free system from the embryos of immature Phaseolus vulgaris seeds. Stable-isotope-labeled GAs were used as substrates and the products were identified by gas chromatography-mass spectrometry. Gibberellin A12-aldehyde was converted to GA4 via non-hydroxylated intermediates and to GA1 via 13-hydroxylated intermediates. 13-Hydroxylation took place at the beginning of the pathway by the conversion of GA12-aldehyde to GA53-aldehyde. The conversion of GA20 to GA5 and GA6 was also shown but no 2beta-hydroxylating activity was found. Endogenous GAs from embryos and testas of 17-dold seeds were re-examined by gas chromatography-selected ion monitoring using stable isotopelabeled GAs as internal standards. Gibberellins A9, A12, A15, A19, A23, A24, and A53 were identified for the first time in P. vulgaris, in addition to GA1, GA4, GA5, GA6, GA8, GA17, GA20, GA29, GA37, GA38 and GA44, which were previously known to occur in this species. The levels of all GAs, except the 2beta-hydroxylated ones, were greater in the embryos than in the testas. Conversely, the contents of GA8 and GA29, both 2beta-hydroxylated, were much higher in the testas than in the embryos. PMID- 24232022 TI - Regulation of mesophyll photosynthesis in intact wheat leaves by cytoplasmic phosphate concentrations. AB - The effect of D-(+)-mannose, inorganic phosphate (Pi) and mannose-6-phosphate on net mesophyll CO2 assimilation rate (A) and stomatal conductance (gs) of wheat (Triticum aestivum L.) leaves was studied. The compounds were supplied through the transpiration stream of detached leaves from plants grown in sand in growth cabinets or glasshouses, with different concentrations of Pi (0.25, 1.0 and 4.0 mM) supplied during growth. In all cases, 10 mM D-(+)mannose caused 40-60% reduction of A within 30 min, though the time courses differed for flag leaves and the sixth leaf on the mainstem of glasshouse- and cabinet-grown plants. D (+)Mannose had a similar effect on A in leaves having a fourfold range in total phosphate content. Effects of D-(+)mannose in reducing gs were always slower than on A. When the CO2 concentration in the leaf chamber was adjusted to maintain intercellular CO2 concentration (Ci) constant as A declined after mannose supply, gs still declined indicating that stomatal closure was not caused by changing Ci. Supplying mannose-6-phosphate at 10 and 1 mM and Pi at 5 and 10 mM concentrations caused rapid reductions in gs and also direct reductions in A. The observed effects of mannose and Pi on assimilation are consistent with the proposed regulatory role of cytoplasmic Pi in determining mesophyll carbon assimilation that has been derived previously using leaf discs, protoplasts and chloroplasts. PMID- 24232023 TI - An unusually high number of direct repeats detected by sequence analysis of the dispersed EcoRI-family fragments in Lupinus luteus L. AB - The Lupinus luteus genome contains a highly repetitive fraction of sequences named the EcoRI family. Two EcoRI molecules, 1071 and 1079 base pairs in length, were cloned, sequenced and compared. Analysis of the internal-sequence organization revealed a number of short direct repeats. Their involvement in the formation of the EcoRI-family fragments is postulated. Evidence is presented for the dispersed type of genomic organization of the EcoRI-family fragments. PMID- 24232024 TI - Anthranilate synthase forms in plants and cultured cells of Nicotiana tabacum L. AB - Tobacco (N. tabacum cv. Xanthi) cell lines contained two forms of anthranilate synthase (AS; EC 4.1.3.27) which could be partially separated by gel-filtration chromatography. One form was resistant to feedback inihibition by 10 MUM tryptophan (trp) while the other form was almost completely inhibited by trp at the same concentration. Cell lines selected as resistant to 5-methyltryptophan (5MT) had more of the trp-resistant AS form. Only the trp-sensitive form was detected in plants regenerated from both normal and 5MT-resistant cell lines. Overexpression of the trp-resistant form in 5MT-resistant tobacco cells disappeared during plant regeneration but reappeared when callus was initiated from the leaves of these plants. The trp-sensitive form was localized in the particulate fraction and the trp-resistant form in the cytosol of tobacco cultured cell protoplasts. The trp-resistant form of AS from tobacco had an estimated MW of 200 000, determined by Sephacryl S-200 chromatography, compared to an estimated MW of 150 000 for the trp-sensitive form. The estimated molecular weights of AS from carrot and corn were 160 000 and 150 000, respectively. Analysis of AS activity from the diploid Nicotiana species Nicotiana otophora (chromosome number 2n=24) by high-performance liquid chromatography showed two activity peaks identical in elution time and trp inhibition characteristics to the activity from N. tabacum (chromosome No. 48). Thus the two enzyme forms found in tobacco did not appear to have originated individually from the progenitor species genomes which combined to make up the tobacco genome. PMID- 24232025 TI - alpha-1,4-glucan phosphorylase forms from leaves of spinach (Spinacia oleracea L.) : II. Peptide patterns and immunological properties. A comparison with other phosphorylase forms. AB - Peptide patterns and immunological properties of the cytoplasmic and chloroplastic alpha-1,4-glucan phosphorylase (EC 2.4.1.1) from spinach leaves have been studied and were compared with those of phosphorylases from other sources. The two spinach leaf phosphorylases were immunologically different; a limited cross-reactivity was observed only at high antigen or antibody concentrations. Peptide mapping of the two enzymes resulted in complex patterns composed of more than 20 fragments; but no peptide was electrophoretically identical in both proteins. Approximately 13 to 15 of the fragments exhibited antigeneity but no cross-reactivity of any peptide was observed. Therefore, the two compartment-specific phosphorylase forms from spinach leaves represent isoenzymes possessing different primary structures. Peptide patterns of potato tuber and rabbit muscle phosphorylase were different from those of the two spinach leaf enzymes. Although the potato tuber phosphorylase resides in the plastidic compartment and is kinetically closely related to the chloroplastic spinach enzyme, it reacted more strongly with the anti-cytoplasmic-phosphorylase immunoglobulin G. Similar results were obtained with rabbit muscle phosphorylase. These observations support the assumption that the chloroplast-specific phosphorylase isoenzyme has a higher structural diversity than does the cytoplasmic counterpart. PMID- 24232026 TI - Ammonium uptake by Chlorella. AB - The preincubation of Chlorella cells with glucose caused a tenfold increase of the maximal uptake rate of ammonium without change in the K m (2 MUM). A similar stimulation of ammonium uptake was found when the cells were transferred to nitrogen-free growth medium. The time-course of uptake stimulation by glucose revealed a lag period of 10-20 min. The turnover of the ammonium transport system is characterized by a half-life time of 5-10 h, but in the presence of light 30% of uptake activity stayed even after 50 h. 6-Deoxyglucose was not able to increase the ammonium uptake rate. These data together were interpreted as evidence for induction of an ammonium transport system by a metabolite of glucose. Mechanistic studies of the ammonium transport system provided evidence for the electrogenic uptake of the ammonium ion. The charge compensation for NH 4 (+) entry was achieved by immediate K(+) efflux from the cells, and this was followed after 1 min by H(+) extrusion. Ammonium accumulated in the cells; the rate of uptake was sensitive to p-trifluoromethoxy-carbonylcyanide-phenylhydrazon and insensitive to methionine-sulfoxime. Uptake studies with methylamine revealed that methylamine transport is obviously catalyzed by the ammonium transport system and, therefore, also increased in glucose-treated Chlorella cells. PMID- 24232027 TI - Purification and molecular and kinetic properties of phosphoenolpyruvate carboxylase from Amaranthus viridis L. leaves. AB - Phosphoenolpyruvate carboxylase (EC 4.1.1.31) was purified 43-fold from Amaranthus viridis leaves by using a combination of ammonium-sulphate fractionation, chromatography on O-(diethylaminoethyl)-cellulose and hydroxylapatite, and filtration through Sepharose 6B. The purified enzyme had a specific activity of 17.1 MUmol.(mg protein)(-1).min(-1) and migrated as a single band of relative molecular weight 100000 on sodium dodecyl sulphate polyacrylamide gel electrophoresis. A homotetrameric structure was determined for the native enzyme. Phosphoenolpyruvate carboxylase from Zea mays L. and A. viridis showed partial identity in Ouchterlony two-dimensional diffusion. Isoelectric focusing showed a band at pI 6.2. Km values for phosphoenolpyruvate and bicarbonate were 0.29 and 0.17 mM, respectively, at pH 8.0. The activation constant (Ka) for Mg(2+) was 0.87 mM at the same pH. The carboxylase was activated by glucose-6-phosphate and inhibited by several organic acids of three to five carbon atoms. The kinetic and structural properties of phosphoenolpyruvate carboxylase from A. viridis leaves are similar to those of the enzyme from Zea mays leaves. PMID- 24232028 TI - Corn phosphoglycolate phosphatase: purification and properties. AB - Phosphoglycolate phosphatase (EC 3.1.3.18), isolated from maize leaf bundle sheath, was purified 200-fold to a specific activity of about 99 MUmol mg(-1) protein . min(-1). The purification procedure included Sephadex G-75 filtration, and diethylaminoethyl-cellulose and Phospho-Ultrogel A6R chromatography. This partially purified enzyme exhibited optimum activity over a broad pH range, from pH 6.3 to pH 8.0. It displayed a very high degree of specificity for phosphoglycolate and required a divalent cation to be active; Mg(2+) was the most effective activator. Saturation curves of the Michaelis-Menten type were observed both with phosphoglycolate (Km=0.57 mmol.l(-1)) and with Mg(2+) (Km=0.015 mmol.l( 1)). The activation constant for Mg(2+) was unchanged when the pH was raised from 7.0 to 8.0. These results indicate that variations of stromal pH and Mg(2+) during the darklight transition could not directly modifity the activity of the phosphoglycolate phosphatase in maize bundle-sheath chloroplasts. The undissociated protein showed a pI of 4.95, as determined by isoelectric focusing. For the native phosphatase a molecular mass of about 61 500 Da was estimated by polyacrylamide gradient gel electrophoresis. The subunit was found to have a relative molecular mass of 31 500 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is concluded that maize phosphoglycolate phosphatase is a dimer. PMID- 24232029 TI - Photoinhibition of photosynthesis in intact bean leaves: role of light and temperature, and requirement for chloroplast-protein synthesis during recovery. AB - Photoinhibition of photosynthesis was induced in intact leaves of Phaseolus vulgaris L. grown at a photon flux density (PFD; photon fluence rate) of 300 MUmol.m(-2).s(-1), by exposure to a PFD of 1400 MUmol.m(-2).s(-1). Subsequent recovery from photoinhibition was followed at temperatures ranging from 5 to 35 degrees C and at a PFD of either 20 or 140 MUmol.m(-2).s(-1) or in complete darkness. Photoinhibition and recovery were monitored mainly by chlorophyll fluorescence emission at 77K but also by photosynthetic O2 evolution. The effects of the protein-synthesis inhibitors, cycloheximide and chloramphenicol, on photoinhibition and recovery were also determined. The results demonstrate that recovery was temperature-dependent with rates slow below 15 degrees C and optimal at 30 degrees C. Light was required for maximum recovery but the process was light-saturated at a PFD of 20 MUmol.m(-2).s(-1). Chloramphenicol, but not cycloheximide, inactivated the repair process, indicating that recovery involved the synthesis of one or more chloroplast-encoded proteins. With chloramphenicol, it was shown that photoinhibition and recovery occurred concomitantly. The temperature-dependency of the photoinhibition process was, therefore, in part determined by the effect of temperature on the recovery process. Consequently, photoinhibition is the net difference between the rate of damage and the rate of repair. The susceptibility of chilling-sensitive plant species to photoinhibition at low temperatures is proposed to result from the low rates of recovery in this temperature range. PMID- 24232030 TI - The two beta-oxidation sites in pea cotyledons : Carnitine palmitoyltransferase: location and function in pea mitochondria. AB - Two sites for beta-oxidation of fatty acids in pea (Pisum sativum L.) cotyledons exist. One site is the microbody, the other the mitochondrion. Mitochondrial beta oxidation of fatty acids is carnitine-dependent. The fatty acid permeates the membrane as palmitoylcarnitine which is formed from cytosolic-side palmitoyl-CoA by a carnitine palmitoyltransferase located on the exterior face of the inner mitochondrial membrane as a peripheral protein. A single-gated pore integral membrane translocator is proposed to exchange the palmitoylcarnitine for carnitine or acetylcarnitine across the membrane. An internal (matrix side) carnitine palmitoyltransferase then reforms palmitoyl-CoA which enters beta oxidation and subsequently the tricarboxylic-acid cycle. PMID- 24232031 TI - Dark respiration in the marine macroalga Chondrus crispus (Rhodophyceae). AB - Dark respiration in the red macroalga Chondrus crispus was studied under a variety of conditions. The components of respiration were examined using selective inhibitors in order to characterise pathways of respiration and examine regulation of respiration in marine macroalgae.In comparison to respiration rates generally reported for higher-plant leaves and roots, the steady-state rate of O2 consumption by this alga, after 30 min dark pretreatment, was found to be quite low (three- to sixfold lower than in higher plants). The addition of uncoupler had only a slight effect on the basal respiration rate, indicating that in these conditions, substrate supply could be limiting respiration. The addition of KCN inhibited respiration by approx. 60%, indicating the presence of alternative oxidase activity. The coefficient of engagement of the alternative pathway (calculated from the data herein) showed that under normal conditions there was little participation of the alternative pathway in O2 consumption. The response of respiration to O2 tension was examined with and without inhibitors and the apparent K m was 17 to 21 MUM. The addition of KCN plus salicylhydroxamic acid almost completely blocked respiration in C. crispus. The hypothesis that respiratory substrate limits respiration in this alga was investigated by measuring respiration rates immediately after periods of photosynthetic activity. It was found that the respiration rate was dependent on the duration of the light period and could increase up to twofold. This stimulated rate of respiration declined in a first-order fashion during the next 20 to 30 min, finally reaching the basal, zero-order rate measured before illumination. These results strongly indicate a change in the nature of the respiratory substrates during this period. No change in the contribution of the alternative pathway of respiration could be detected following light pretreatment. PMID- 24232032 TI - Synchronization of protoplasts from Glycine max (L.) Merr. and Brassica napus (L.). AB - Cells of Glycine max originating in a suspension culture and cells of Brassica napus prepared from hypocotyls were synchronized. Synchronization was achieved by preparing protoplasts in the usual way and subsequently letting the protoplasts regenerate into cells by removing the cell-wall-digesting enzymes. More than 70% of the cells had divided synchronously at the end of the first cycle as determined by the mitotic index. The high frequency of mitosis critically depended on the osmolality of the medium. The duration of the S-phase was estimated by measuring the activity of thymidylate kinase as well as incorporation of [(3)H]deoxythymidine into acid-insoluble material. The data indicate that synchronization is induced by resetting the cell cycle. PMID- 24232033 TI - Freezing of isolated thylakoid membranes in complex media : III. Differences in the pattern of inactivation of photosynthetic reactions. AB - Chloroplast thylakoid membranes isolated from spinach leaves (Spinacia oleracea L. cv. Monatol) were subjected to a freeze-thaw treatment in a buffered medium containing 70 mM KCl, 30 mM NaNO3 and 20 mM K2SO4 in different combinations. In the presence of the three predominant inorganic electrolytes, inactivation of photophosphorylation was mainly caused by a decrease in the capacity of the photosynthetic electron transport; release of proteins from the membranes was not manifest and light-induced H(+) gradient and proton permeability were largely unaffected. Omission of nitrate from the medium had little effect. When either sulfate or chloride or both were omitted prior to freezing, inactivation of photophosphorylation was correlated with stimulation of the phosphorylating electron flow, marked increase in H(+) permeability and loss of the ability of the thylakoids to accumulate protons in the light. In the absence of sulfate, uncoupling was mainly a consequence of the dissociation of chloroplast coupling factor (CF1). Partial restoration of proton impermeability and pH gradient occurred upon the addition of N,N'-dicyclohexylcarbodiimide (DCCD). When sulfate was present but chloride omitted, CF1 remained attached to the membranes and the addition of DCCD had no effect, indicating that the increase in proton efflux was caused by a different mechanism. It is concluded that sulfate stabilizes the CF1 and prevents its release from the membranes, but KCl is also necessary for maintaining the low permeability of the membranes to protons. The importance of complex media for investigations on isolated biomembrane systems is stressed. PMID- 24232034 TI - Nocturnal water storage in plants having Crassulacean acid metabolism. AB - Measurements of water uptake and transpiration, during the dark period of plants having Crassulacean acid metabolism (CAM) allow calculation of leaf-volume changes (DeltaV). Nocturnal leaf-volume changes of CAM plants have also been reported in the literature on the basis of waterdisplacement measurements. A third way of estimation is from measurements of turgor changes and cellular water storage capacity using the pressure probe, cytomorphometry and the Scholander pressure chamber. An extension of the interpretation of results reported in the literature shows that for leaf succulent CAM plants the three different approaches give similar values of DeltaV ranging between 2.3 and 10.7% (v/v). It is evident that nocturnal malic-acid accumulation osmotically drives significant water storage in CAM leaf tissue. PMID- 24232035 TI - Radiological diagnosis and management of epistaxis. AB - The majority of episodes of spontaneous posterior epistaxis treated with embolisation are idiopathic in nature. The angiographic findings are typically normal. Specific angiographic signs are rare and may include the following: a tumour blush, telangiectasia, aneurysm, and/or extravasation. Selective internal carotid artery (ICA) angiography may show rare causes of epistaxis, such as traumatic or mycotic aneurysms, which require different treatment approaches. Complete bilateral selective external and internal carotid angiograms are essential to evaluation. The images should be analysed for detection of central retinal blush in the external carotid artery (ECA) and anastomoses between the branches of the ECA and ICA. Monocular blindness and stroke are two of the most severe complications. Embolisation aims to decrease flow to the bleeding nasal mucosa while avoiding necrosis of the nasal skin and palate mucosa. Embolisation is routinely performed with a microcatheter positioned in the internal maxillary artery distal to the origin of the meningeal arteries. A guiding catheter should be placed in the proximal portion of the ECA to avoid vasospasm. Embolisation with microparticles is halted when the peripheral branches of the sphenopalatine artery are occluded. The use of coils is not recommended because recurrent epistaxis may occur due to proximal embolization; moreover, the option of repeat distal embolisation is lost. The success rate of embolisation therapy (accounting for late recurrence of bleeding) varies between 71 and 94 %. Results from endoscopic surgery are quite comparable. When epistaxis is refractory to nasal packing or endoscopic surgery, embolisation is the treatment of choice in some centres. PMID- 24232036 TI - Endovascular embolization of an aberrant bronchial artery originating from the vertebral artery in a patient with massive hemoptysis. AB - Endovascular embolization has become an established procedure for the management of massive or recurrent hemoptysis. The bronchial, nonbronchial systemic and pulmonary arteries are possible sources of bleeding, and the major sources of bleeding are the bronchial arteries (BAs). However, the locations of ostia of the BAs have numerous anatomical variations, which can make it technically challenging to identify a bleeding artery. We herein present a rare case of a left BA that originated from the ipsilateral vertebral artery in a patient with massive hemoptysis caused by active tuberculosis. Transarterial embolization was successfully performed, and the hemoptysis has been controlled for 2 months. PMID- 24232037 TI - Radiofrequency ablation after arterial injection of miriplatin-iodized oil suspension into swine liver: ablative zone size and tissue platinum concentration. AB - PURPOSE: To evaluate whether arterial injection of miriplatin-iodized oil suspension facilitates ablative zone expansion by radiofrequency (RF) ablation using a Cool-Tip electrode and to provide effective tissue platinum concentration in the normal swine liver. MATERIALS AND METHODS: RF ablation was performed at three sites of each liver. RF ablation alone was performed in two animals (control). Ablation was performed after arterial injection of iodized oil (iodized-oil group) or a miriplatin-iodized oil suspension (miriplatin group) in two animals each. Long- and short-axis diameters of the ablative zone were measured. In the miriplatin group, tissue platinum concentrations were measured in the ablative, surrounding hyperemic rim, and nonablative zones. RESULTS: The mean long- and short-axis diameters of ablative zones were 27.0 +/- 3.1 and 18.0 +/- 0.6 mm in the control. Although the long-axis diameter (30.2 +/- 2.8 mm, p = 0.07) showed no significant expansion, the short-axis diameter (20.8 +/- 2.6 mm, p = 0.04) was significantly expanded more in the iodized-oil group than in the control. Ablative zone sizes were largest in the miriplatin group. The long-axis diameter (33.5 +/- 2.4 mm, p = 0.01) was significantly larger than that in the control. The short-axis diameter (27.2 +/- 1.9 mm, p = 0.004) was significantly larger than that of the iodized-oil group. Tissue platinum concentrations showed an effective antitumor effect (>=9 MUg/g) in ablative (16.5 +/- 5.7 MUg/g), surrounding hyperemic rim (18.0 +/- 5.1 MUg/g), and nonablative zones (mean 22.2 +/- 5.7 MUg/g) (p = 0.21). CONCLUSION: Arterial injection of miriplatin-iodized oil suspension can expand the ablative zone size and provide effective tissue platinum concentration on tumor control in the ablative zones and their surrounding hyperemic rim. PMID- 24232038 TI - Evaluation of split renal function before and after renal arterial embolization for angiomyolipoma using absolute ethanol. AB - PURPOSE: Transcatheter arterial embolization (TAE) with absolute ethanol is widely accepted as a therapeutic procedure for renal angiomyolipoma (AML). We aim to evaluate the split renal function before and after AE for renal AML by using 99m-technetium (99mTc)-mercaptoacetyltriglycine 3 (MAG3) renography. METHODS: This study was approved by the Institutional Review Board. The study population comprised 11 renal AML patients (three males, eight females, age 55.1 +/- 13.8 years, AML in eight right and three left kidneys) who received unilateral renal TAE with absolute ethanol from April 2002 to January 2013. Blood renal function (i.e. serum creatinine and estimated glomerular filtration rate [eGFR] and split effective renal plasma flow [ERPF]) calculated on 99mTc-MAG3 renography was compared before and within 1 week after renal AE. Statistical analysis was calculated using Wilcoxon signed-ranked test. RESULTS: TAE for renal AML was technically successful in all patients. Serum creatinine and eGFR did not change before and after TAE. ERPF on the embolized kidney did not change before (127.3 +/- 60.8 ml/min) and after (127.6 +/- 47.4 ml/min) TAE (p = 0.9726). ERPF on the nonembolized kidney showed a statistically significant increase before (152.5 +/- 46.8 ml/min) and within 1 week after (169.1 +/- 41.5 ml/min) TAE (p = 0.0093 and p < 0.05, respectively). CONCLUSION: TAE for renal AML may not induce renal dysfunction on the embolized kidney and may immediately increase the renal blood flow of the nonembolized kidney. PMID- 24232039 TI - Endovascular treatment of ruptured abdominal aortic aneurysms: is now EVAR the first choice of treatment? AB - OBJECTIVE: This study was designed to evaluate the effectiveness of endovascular treatment (EVAR) for ruptured abdominal aortic aneurysms (rAAAs). METHODS: Between September 2005 and December 2012, 44 patients with rAAA suitable for endovascular repair underwent emergency EVAR. We did not consider hemodynamic instability to be a contraindication for EVAR. RESULTS: Successful stent-graft deployment was achieved in 42 patients, whereas 2 required open surgical conversion. The overall 30-day mortality was 10 of 44 patients (5/34 in stable patients, 5/10 in unstable patients). Postoperative complications were observed in 7 of 44 patients (16 %): 5 patients developed abdominal compartment syndrome requiring decompressive laparotomy; 1 patient developed bowel ischemia; 1 patient had limb ischemia, and 1 had hemodynamic shock. Mean length of intensive care unit stay was 2.9 (range 2-8) days, and mean length of hospital stay was 8.6 (range 0-18) days. At a mean follow-up of 22.2 (range 1-84) months, the overall incidence of endoleak was 23.5 %: 1 type I and 7 type II endoleaks. CONCLUSIONS: Our study demonstrates that EVAR of rAAA is associated with acceptable mortality and morbidity rates in dedicated centers. PMID- 24232040 TI - General theory of predictive dosimetry for yttrium-90 radioembolization to sites other than the liver. AB - Modern advances in interventional radiology and nuclear medicine may now allow for safe and effective 90Y radioembolization to sites other than the liver. A general theory of predictive dosimetry based on the MIRD schema is proposed, adapted from the original partition model for liver 90Y radioembolization. PMID- 24232041 TI - Symptomatic perforation of a Gunther Tulip inferior vena cava filter with subsequent strut fracture and pulmonary embolization. PMID- 24232042 TI - General theory of predictive dosimetry for yttrium-90 radioembolization to sites other than the liver: reply. PMID- 24232043 TI - Endovascular Repair of a Complex Splenic Artery Aneurysm Using a Multilayer Stent. PMID- 24232044 TI - Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society [IEHS])-Part 2. PMID- 24232045 TI - Initial experience with a new articulating energy device for laparoscopic liver resection. AB - BACKGROUND: Although significant advances have been made in laparoscopic liver resection (LLR), most techniques still rely on multiple energy devices and staplers, which increase operative costs. The aim of this study was to report the initial results of a new multifunctional energy device for hepatic parenchymal transection. METHODS: Fourteen patients who underwent LLR using this new device were compared to 20 patients who had LLR using current laparoscopic techniques (CL). Data were collected prospectively. RESULTS: The groups were similar demographics and tumor type and size. Although the type of resection was similar between the groups, the parenchymal transection time was less in the Caiman group (32 +/- 5 vs. 63 +/- 4 min, respectively, p = 0.0001). The operative time was similar (194 +/- 21 vs. 233 +/- 16 min, respectively, p = 0.158). There was reduction of the number of advanced instrumentation used in the Caiman group, including the staplers. Estimated blood loss, size of surgical margin, and hospital stay were similar. There was no mortality, and morbidity was 7 % in the Caiman and 20 % in the CL group. CONCLUSIONS: This initial study shows that the new device is safe and efficient for LLR. Its main advantage is shortening of hepatic parenchymal transection time. This has implications for increasing efficiency and cost saving in LLR. PMID- 24232046 TI - Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer. AB - BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins. PMID- 24232047 TI - The ergonomics of women in surgery. AB - BACKGROUND: Among surgeons who regularly perform minimally invasive surgery, as many as 87 % report injuries or symptoms related to job performance. Operating room and instrument design have traditionally favored surgeons who are taller and who possess hands that are, in general, large and strong. We hypothesize that women may be experiencing more ergonomic difficulties than men for whom the operating room and surgical instruments, although uniformly perilous, more traditionally have accommodated. METHODS: A 23-item web-based survey was offered via email to 2,000 laparoscopic surgeons and fellows currently practicing. The survey addressed four categories: demographics, physical symptoms, ergonomics, and environment/equipment. Key questions allowed us to identify which body part experienced which symptoms. RESULTS: There was a 15.7 % overall response rate. Among respondents, 17 % (54/314) were female. Women were significantly younger, shorter, had smaller glove size, and fewer years in practice than men surveyed (all p values < 0.0001). Of women reporting, 86.5 %-comparable to men-attribute physical discomfort to laparoscopic operating. Female surgeons are more likely to receive treatment for their hands, which includes the wrist, thumb, and fingers (odds ratio 3.5, p = 0.028). When men and women of the same glove size were compared, women with a larger glove size (7-8.5) reported more cases of treatment for their hands than men of the same glove size. (21 vs. 3 %, p = 0.016). Women who wore a size 5.5-6.5 surgical glove reported significantly more cases of discomfort in their shoulder area (neck, shoulder, upper back) than men who wore the same size surgical glove (77 vs. 27 %, p = 0.004). CONCLUSIONS: Women surgeons are experiencing more discomfort and treatment in their hands than male surgeons. Redesign of laparoscopic instrument handles and improvements to table height comprise the most promising solutions to these ergonomic challenges. PMID- 24232048 TI - A proposed classification for uniform endoscopic description of surgical fundoplication. AB - BACKGROUND: Objective assessment of postfundoplication anatomy is of utmost importance especially if reoperative intervention is being planned. There is a lack of uniformity in the description of endoscopic findings in these patients.The purpose of this study was to propose a classification for standardized endoscopic reporting of postfundoplication anatomy. METHODS: After institutional review board approval, preoperative endoscopic findings of patients who underwent reoperative intervention from 1992 to 2011 were reviewed a nd classified. The classification included four factors:E (distance of GEJ to crus), S (amount of gastric tissue between the GEJ and fundoplication), F (fundoplication configuration), and P (paraesophageal hernia). RESULTS: The endoscopic findings of 310 patients who underwent reoperative antireflux surgery were classified using the newly proposed classification model. A significant increase in the number of procedures was noted over the years.There was no change in presenting symptoms and patterns of failure over the years. The classification model was easily applicable to previous endoscopy reports. There was good symptom association with our classification model. DISCUSSION: An endoscopic anatomical classification is proposed for description of failed fundoplication. With this classification, we hope to fill the gap in developing a uniform classification of failed fundoplications. Further studies addressing widespread applicability and outcome analysis are needed. PMID- 24232049 TI - Nationwide outcomes of nontrauma splenectomy. AB - INTRODUCTION: Due to the impact of LeapFrog and many scientific publications, regionalization for solid-organ operations gained momentum in the early 2000s. This study examines the effects of regionalization for medically indicated, nontrauma splenectomies (NTSs) in the USA. METHODS: The Nationwide Inpatient Sample (NIS) data were analyzed for NTS based on International Classification of Disease Ninth Revision Clinical Modification codes for 1998-1999 (the 1990s) and 2008-2009 (the 2000s). The hospitals in the NIS were stratified by volume and divided into high volume (HV), medium volume, and low-volume (LV) terciles based on the annual volume of splenectomies performed (<5, 5-10, and 11+, respectively). Demographics, comorbidities, complications, admission status, and in-patient mortality were recorded. Univariate and multivariate statistical analyses were utilized. RESULTS: NIS recorded 4,293 NTS performed in the 1990s and 3,384 in the 2000s. Despite the decrease in operative volume, regionalization did not occur: in the first decade 30, 37, and 33 % of cases occurred in LV center (LVC), medium volume center, and HV center (HVC), respectively, compared with 34, 30, and 36 % in the second decade (p < 0.001). Patients were older in low-volume hospitals (LVC) than in high-volume hospitals (HVC) in both decades (in the 1990s: 45.3 vs. 52.7 years, p < 0.001; in the 2000s: 49.1 vs. 54.5 years, p < 0.001). The Charlson Comorbidity Index scores were not different in LVC compared with HVC in both decades (the 1990s: 1.31 vs. 1.23, p = 0.73; the 2000s: 1.54 vs. 1.41, p = 0.72). In both decades, LVC had more emergent admissions than HVC (20.3 vs. 16.8 %, p = 0.03; 28.8 vs. 19.5 %, p < 0.001). Complication rates were higher in LVC in both decades (the 1990s: 16.9 vs. 13.6 %, p = 0.02; the 2000s: 19.8 vs. 15.5 %, p = 0.006). Mortality was not different for HVC and LVC in both decades (the 1990s: 3.75 vs. 4.27, p = 0.49; the 2000s: 2.94 vs. 4.03, p = 0.15). CONCLUSIONS: NTS has not been affected by regionalization, which is dissimilar to other solid-organ abdominal procedures. Indeed, the benefit of regionalization for splenectomy has not been established. PMID- 24232050 TI - Comparison of immediate postoperative pain after transvaginal versus traditional laparoscopic cholecystectomy. AB - BACKGROUND: Transvaginal cholecystectomy (TVC) is the most common natural orifice transluminal surgery (NOTES) performed in women, yet there is a paucity of data on intraoperative and immediate postoperative pain management. Previous studies have demonstrated that NOTES procedures are associated with less postoperative pain and faster recovery times. This study analyzes intraoperative and postoperative opioid use for TVC compared with traditional four-port laparoscopic cholecystectomies (LCs). METHODS: This is a retrospective analysis of consecutive TVC and LC female patients between August 2009 and August 2012 in an academic institution. We compared demographics, intraoperative and postoperative opioid use and times in the operating room (OR) and in the post anesthesia care unit (PACU). RESULTS: A total of 68 TVC and 67 LC patients were included in this study. The TVC and LC groups were similar in terms of age (both 41 years) and body mass index (29 and 31 kg/m2, respectively). The intraoperative preparation, surgical, and emergence times were significantly longer for the TVC than for the LC (p <= 0.01). Compared with the LC group, the intraoperative opioid requirement was significantly greater (TVC 27 mg vs. LC 25 mg; p = 0.003), but after adjusting for anesthesia time, the difference in OR opioid consumption became non significant (p = 0.08). The PACU opioid requirement (TVC 2.5 vs. LC 5 mg; p = 0.04) was significantly lower for the TVC group, and a greater proportion of patients did not need any pain medications (TVC 38 % vs. LC 21 %; p = 0.04), compared with the LC group. The average PACU pain scores were not significantly different between the groups (p = 0.45). CONCLUSION: TVC patients did not experience more pain than LC patients. Although the average pain scores of TVC patients did not differ from those of the LC patients, TVC patients did require less pain medication in the PACU. PMID- 24232051 TI - Underwater endoscopic mucosal resection of colorectal neoplasia is easily learned, efficacious, and safe. AB - BACKGROUND: Underwater endoscopic mucosal resection (UEMR) without submucosal injection is a novel endoscopic procedure. It is not known if UEMR can be easily taught and learned, and the efficacy and safety of UEMR has not been demonstrated at multiple medical centers. Our aims were to demonstrate that (1) UEMR is a technique that can be easily learned by an endoscopist trained in traditional EMR, (2) endoscopic ultrasound (EUS) may not be required before UEMR, and (3) UEMR is an efficacious and safe method for resection of large or flat neoplastic colorectal lesions. METHODS: An experienced interventional endoscopist began performing UEMR after observing UEMR procedures. Colorectal UEMR was performed using a pediatric colonoscope with a cap, a waterjet, and a 'duck-bill' snare using blended current. Submucosal injection was not used. Patient data were collected prospectively. RESULTS: A total of 21 patients (17 men, mean age 64.9 years, range 51-83) referred for polypectomy of large colorectal lesions underwent UEMR. A total of 43 colorectal lesions with a mean size of 20 mm (range 8-50) were resected by UEMR. Lesions were found in the right colon (N = 16), transverse colon (N = 5), left colon (N = 19), and rectum (N = 3). Pathology demonstrated tubular adenoma (N = 29), tubulovillous adenoma (N = 5), high-grade dysplasia (N = 3), serrated sessile adenoma without dysplasia (N = 3), and non neoplastic tissue (N = 3). EUS was used in only two cases of rectal neoplasia (4.7 %). Of the UEMRs, 97.7 % were successful with complete resection of colorectal polyps. The only adverse event was one case (2.3 %) of delayed post UEMR bleeding. CONCLUSIONS: UEMR was easily learned by an endoscopist already skilled in conventional EMR. EUS may not be required prior to most UEMR procedures. UEMR appears to be an efficacious and safe alternative to traditional EMR or ESD for large or flat colorectal neoplasms. PMID- 24232052 TI - Peroral endoscopic myotomy for idiopathic achalasia: randomized comparison of water-jet assisted versus conventional dissection technique. AB - BACKGROUND: Peroral endoscopic myotomy (POEM) has recently been introduced as a promising alternative to laparoscopic Heller myotomy for idiopathic achalasia. Several proposed technical modifications are yet to be tested in randomized trials. OBJECTIVE: The objective of our study was to evaluate efficacy and safety of water-jet (WJ) assisted POEM versus the conventional (C) technique. The clinical trial registration number is NCT01742494. METHODS: A prospective randomized trial was carried out in Zhongshan Hospital, Fudan University (Shanghai, China), in 100 consenting achalasia patients between August 2011 and April 2012. Patients eligible for POEM were randomized to use of either the HybridKnife (WJ group) or the conventional technique using injection and triangle tip knife interchangeably (C group). RESULTS: A total of 100 patients with comparable characteristics between groups were included. Procedure time was significantly shorter for the WJ group (22.9 +/- 6.7 vs. 35.9 +/- 11.7 min; p < 0.0001), mostly due to less replacement of accessories (2.0 +/- 2.4 vs. 19.2 +/- 7.6; p < 0.0001). Injection volume was larger in the WJ group (45.3 +/- 10.2 vs. 35.2 +/- 9.5 ml; p < 0.0001) and was associated with fewer minor bleeding episodes (3.6 +/- 1.8 vs. 6.8 +/- 5.2; p < 0.0001). No severe complications occurred; one case of cutaneous emphysema occurred in the WJ group, and four cases occurred in the C group (p = 0.17), three cases of pneumonia were encountered in the C group and none in the WJ group (p = 0.24). Treatment success (Eckardt score <=3) was achieved in 96.5 % of patients, with no significant differences between groups. CONCLUSIONS: The use of the HybridKnife leads to a significant decrease in POEM procedure time and facilitates reinjection, possibly contributing to a lower rate of minor intra-procedural bleeding. PMID- 24232053 TI - Endoscopic submucosal dissection versus transanal endoscopic microsurgery for the treatment of early rectal cancer. AB - BACKGROUND: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that can be used to treat early rectal cancer. OBJECTIVE: The aim of this study was to compare clinical efficacy between ESD and TEM for the treatment of early rectal cancer. METHODS: Between July 2008 and August 2011, 24 patients with early rectal cancers were treated by ESD (11) or TEM (13) at the Cancer Institute of Sao Paulo University Medical School (Sao Paulo, Brazil). Data were analyzed retrospectively according to database and pathological reports, with respect to en bloc resection rate, local recurrence, complications, histological diagnosis, procedure time and length of hospital stay. RESULTS: En bloc resection rates with free margins were achieved in 81.8 % of patients in the ESD group and 84.6 % of patients in the TEM group (p = 0.40). Mean tumor size was 64.6 +/- 57.9 mm in the ESD group and 43.9 +/- 30.7 mm in the TEM group (p = 0.13). Two patients in the TEM group and one patient in the ESD group had a local recurrence. The mean procedure time was 133 +/- 94.8 min in the ESD group and 150 +/- 66.3 min in the TEM group (p = 0.69). Mean hospital stay was 3.8 +/- 3.3 days in the ESD group and 4.08 +/- 1.7 days in the TEM group (p = 0.81). LIMITATIONS: This was a non-randomized clinical trial with a small sample size and selection bias in treatment options. CONCLUSION: ESD and TEM are both safe and effective for the treatment of early rectal cancer. PMID- 24232054 TI - Optimization of near-infrared fluorescence cholangiography for open and laparoscopic surgery. AB - BACKGROUND: During laparoscopic cholecystectomy, common bile duct (CBD) injury is a rare but severe complication. To reduce the risk of injury, near-infrared (NIR) fluorescent cholangiography using indocyanine green (ICG) has recently been introduced as a novel method of visualizing the biliary system during surgery. To date, several studies have shown feasibility of this technique; however, liver background fluorescence remains a major problem during fluorescent cholangiography. The aim of the current study was to optimize ICG dose and timing for NIR cholangiography using a quantitative intraoperative camera system during open hepatopancreatobiliary (HPB) surgery. Subsequently, these results were validated during laparoscopic cholecystectomy using a laparoscopic fluorescence imaging system. METHODS: Twenty-seven patients who underwent NIR imaging using the Mini-FLARE image-guided surgery system during open HPB surgery were analyzed to assess optimal dosage and timing of ICG administration. ICG was intravenously injected preoperatively at doses of 5, 10, and 20 mg, and imaged at either 30 min (early) or 24 h (delayed) post-injection. Next, the optimal doses found for early and delayed imaging were applied to two groups of seven patients (n = 14) undergoing laparoscopic NIR fluorescent cholangiography during laparoscopic cholecystectomy. RESULTS: Median liver-to-background contrast was 23.5 (range 22.1-35.0), 16.8 (range 11.3-25.1), 1.3 (range 0.7-7.8), and 2.5 (range 1.3-3.6) for 5 mg/30 min, 10 mg/30 min, 10 mg/24 h, and 20 mg/24 h, respectively. Fluorescence intensity of the liver was significantly lower in the 10 mg delayed imaging dose group compared with the early imaging 5 and 10 mg dose groups (p = 0.001), which resulted in a significant increase in CBD-to-liver contrast ratio compared with the early administration groups (p < 0.002). These findings were qualitatively confirmed during laparoscopic cholecystectomy. CONCLUSION: This study shows that a prolonged interval between ICG administration and surgery permits optimal NIR cholangiography with minimal liver background fluorescence. PMID- 24232056 TI - Factors associated with 30-day readmission and long-term efficacy of enteral stent placement for malignancy. AB - BACKGROUND: Readmissions to the hospital within 30 days of discharge (30-day readmission rate) may impact stent use in palliative treatment of cancer. OBJECTIVE: Our objective was to investigate the incidence of readmission and factors predicting readmissions and long-term outcomes in patients with self expanding metal stents (SEMS) placed for malignant obstruction. METHODS: Retrospective analysis of all patients who underwent placement of SEMS from 2007 to 2012 for malignant esophageal, gastroduodenal, and colonic obstruction. Incidence and variables associated with 30-day readmission and long-term outcomes were determined. RESULTS: A total of 191 patients underwent stent placement. The 30-day readmission rate was 17.3 % (N = 33). Readmissions were for stent-related complications in 7.3 % (N = 14) and non-stent-related complications in 9.9 % (N = 19). Stent placement was technically successful in 185 of 191 (96.9 %) and clinically successful in 170 of 191 (89.0 %) patients. On long-term follow-up, 32 (16.8 %) patients needed re-intervention. The mean stent patency was 142 days. Readmission within 30 days was independently associated with development of early complications (<7 days) following stent placement (odds ratio [OR] 5.90; 95 % confidence interval [CI] 2.04-17.1), while the stent location did not impact readmission risk. On Cox regression analysis, American Society of Anesthesiologists physical classification (OR 1.36; 95 % CI 1.02-1.87) and stent location in the esophagus (OR 1.82; 95 % CI 1.10-3.02) were independently associated with long-term mortality. CONCLUSIONS: Early complications following stent placement increase the risk of 30-day readmission. SEMS is efficacious long term for palliation of malignant gastrointestinal obstruction. PMID- 24232057 TI - Middle ear myoclonus cured by selective tenotomy of the tensor tympani: strategies for targeted intervention for middle ear muscles. AB - OBJECTIVE: To describe a case of middle ear myoclonus that was successfully cured by selective transection of the tensor tympani (TT) without sectioning the stapedius tendon (ST) and to review previously reported cases, elucidating precipitating factors for interventions targeting middle ear muscles. DATA SOURCES: One case we encountered and a recent systematic review published in 2012. STUDY SELECTIONS: In addition to our case, 23 cases identified by the previous systematic review regarding middle ear myoclonus in which surgical interventions were conducted. DATA SYNTHESIS: Outcomes for selective tenotomy of TT or ST were analyzed focusing on the following 6 preoperative factors: 1) history of facial palsy, 2) provoking factors for tinnitus, 3) auscultation of the ear, 4) movement of the ear drum, 5) complication with palatal myoclonus, and 6) confirmation of myoclonus during surgery. Among these, the first 2 factors represented significant factors for selective tenotomy of ST (p < 0.05 and p < 0.01, respectively). Furthermore, no auscultation of the ear was significant for selective tenotomy (p < 0.01), specifically for ST. Confirmation of muscle contraction during surgery contributed significantly (p < 0.01) to targeted intervention, but selective tenotomy of TT was successfully performed in 3 cases without such confirmation by confirming variations in compliance with tympanometry CONCLUSION: Assessment of the history of facial palsy, provoking factor of tinnitus, auscultation of the ear, and confirmation of myoclonus during surgery appear helpful in predicting which middle ear muscle is undergoing myoclonus. Furthermore, long-time-based tympanometry offers objective information for planning targeted intervention for middle ear muscles and clarifying clinical outcomes. PMID- 24232055 TI - The end of robot-assisted laparoscopy? A critical appraisal of scientific evidence on the use of robot-assisted laparoscopic surgery. AB - BACKGROUND: Robot-assisted laparoscopy has been used in a wide variety of surgical fields; however, the financial costs involved are high and convincing proof of superiority in terms of quality of life, cost effectiveness and survival is often lacking. Possibly, there might be small benefits for the patient or for the surgeon's health that might warrant the use of robotics in limited fields of surgery. METHODS: We performed a critical appraisal of the literature, searching for scientific evidence supporting the use of robotics in daily laparoscopic surgery. RESULTS: Convincing evidence supporting the use of robotics is lacking. CONCLUSION: In an era of worldwide economic crisis, it is about time to start a critical discussion as to whether we should drastically limit, or even abandon, the use of robot-assisted laparoscopic surgery and focus on more cost-effective strategies of healthcare improvement. We suggest the use of robotics should be limited to well-powered, randomized clinical trials in a limited field of research. PMID- 24232058 TI - Promising clinical results of an innovative self-crimping stapes prosthesis in otosclerosis surgery. AB - OBJECTIVES: This clinical study was performed to retrospectively analyze the hearing improvement of patients with otosclerosis who underwent stapesplasty with a novel nitinol prosthesis in comparison with the use of already established prostheses (titanium and clip prostheses) and to evaluate the suitability of the nitinol prosthesis for ear surgeons with limited experience in otosclerosis surgery. STUDY DESIGN: Retrospective data analysis. SETTING: Tertiary referral center. PATIENTS: Sixty patients who underwent otosclerosis surgery between July 1, 2010, and June 30, 2012, in the ENT department of the University of Munich. Two patients were operated on both sides. For four patients, the stapesplasty was a revision surgery. INTERVENTIONS: Sixty-two procedures of otosclerosis surgery were performed by 6 ear surgeons, one of whom with profound experience in stapesplasty. MAIN OUTCOME MEASURES: 1) Postoperative air-bone gap, determined for all surgeons together as well as itemized for the experienced and the nonexperienced stapes surgeons; 2) closure of the air-bone gap in 10 dB bins; and 3) change of high-tone bone-conduction level. RESULTS: Pure-tone audiometry documented less postoperative air-bone gap and a higher percentage of air-bone gap closure when using the nitinol prosthesis, especially in comparison with the clip prosthesis. Also, nonexperienced stapes surgeons received better audiometric results when using the novel nitinol prosthesis. CONCLUSIONS: Clinical evaluation suggests the novel nitinol prosthesis to be a promising tool in otosclerosis surgery for experienced stapes surgeons as well as for ear surgeons with limited experience in stapes surgery. PMID- 24232059 TI - First experience with the fiber-enabled CO2 laser in stapes surgery and a comparison with the "one-shot" technique. AB - OBJECTIVE: To compare bone conduction after fiber-enabled CO2 laser perforation of the stapes footplate with conduction after the "one-shot" technique during stapedotomy in patients with otosclerosis. STUDY DESIGN: Retrospective clinical study. SETTING: Tertiary reference center. MATERIALS AND METHODS: We evaluated data from 178 patients who had undergone primary stapedotomy for suspected stapedial ankylosis. The stapes footplate was perforated using a fiber-enabled CO2 laser in 89 patients and the "one-shot" technique in the other 89. Only consecutive surgery was considered. Bone conduction thresholds were determined at 0.5, 1, 2, and 4 kHz on the first and third postoperative days in all patients; 172 patients were followed up after 1 month. Audiograms were compared with preoperative bone conduction. RESULTS: The postoperative bone conduction threshold on Day 1 was significantly worse at almost all frequencies. At 0.5 and 2 kHz, it improved within a month and was significantly different from the preoperative value. Bone conduction threshold at 4 kHz showed the greatest deterioration immediately after surgery, improving considerably in 1 month but remaining worse than at baseline. Only at 1 kHz was there no significant immediate hearing loss. Direct comparison of the fiber-enabled CO2 laser and the "one-shot" technique showed no statistically significant differences. CONCLUSION: Compared with the "one-shot" technique, the fiber-enabled CO2 laser can be used safely in stapes surgery, without great risk to the patient. In our opinion, it has practical advantages, especially in difficult anatomic conditions. PMID- 24232060 TI - Incidence of sudden sensorineural hearing loss. AB - OBJECTIVE: Recent data regarding the incidence of sudden sensorineural hearing loss (SSNHL) in the United States is lacking. The objective of this study was to assess the current day incidence of SSNHL in the United States using data from a medical and pharmaceutical claims database containing information for more than 60 million unique patients. STUDY DESIGN: Population-based cross-sectional analysis. SETTING: Inpatient and outpatient. PATIENTS: Patients in the database are reported to be representative of the national, commercially insured population on a variety of demographic measures including age, sex, health plan type, and geographic location. RESULTS: During 2006 and 2007, the annual incidence of SSNHL was 27 per 100,000 in the United States. The incidence increased with increasing age, ranging from 11 per 100,000 for patients younger than 18 years to 77 per 100,000 for patients 65 years and older. There was an overall slight male preponderance with a male-to-female ratio of 1.07:1. This was more pronounced in patients 65 years and older, with a ratio of 1.30:1. CONCLUSION: More than 66,000 new cases of SSNHL are seen annually in the United States. The disorder is more common in men and the elderly. PMID- 24232061 TI - Discovery of a large deletion of KAL1 in 2 deaf brothers. AB - OBJECTIVES: Kallmann syndrome (KS) usually combines an anosmia and a hypogonadotrophic hypogonadism. Hearing impairment was described in a few cases of KS. Our objective is to describe an unusual presentation of KS in 2 cases and to explore the pattern of inheritance in this family. PATIENTS: Two brothers presented with a sensorineural hearing impairment associated with cryptorchidism and abnormal movements. RESULTS: Genome-wide array analysis identified a large deletion of KAL1 in both patients confirming the diagnosis of Kallmann syndrome. The absence of familial history has been explained by a somatic mosaicism identified in their mother. CONCLUSION: The description of a hearing defect in 2 brothers with Kallmann syndrome allows asserting that deafness is part of the clinical features of this disease and must lead the physician to monitor the hearing function of Kallmann patients. PMID- 24232062 TI - Speech and language outcomes of cochlear implantation in children with isolated auditory neuropathy versus cochlear hearing loss. AB - OBJECTIVE: Children with auditory neuropathy (AN) have variable hearing on pure tone testing, and the presence of speech and language delays often play a major role in the decision to offer cochlear implantation (CI) in this population. Despite this fact, the speech and language outcomes in this group after CI are not well described. This study compares speech and language outcomes after CI in a subset of the pediatric AN population that does not have a confounding cognitive disorder with those of their peers with cochlear hearing loss (CoHL). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Seventeen pediatric patients with AN who received a CI and a group of children with CoHL who received a CI were the subjects of this study. The 2 groups demonstrated similar ages at implant. Children with cognitive delays were excluded from each group. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: All subjects were evaluated preoperatively and postoperatively with standardized age appropriate speech and language measures, including the Expressive Vocabulary Test (EVT), Peabody Picture Vocabulary Test (PPVT), and Preschool Language Scale (PLS). RESULTS: There was no significant difference between the groups on age of activation of the CI. Children with a diagnosis of AN had a significantly lower unaided pure tone average preoperatively as compared with children with cochlear hearing loss; however, there was no significant difference between the groups on either their preimplantation or postimplantation speech and language scores. CONCLUSION: Children with a diagnosis of AN without associated cognitive or developmental disorders have speech and language outcomes comparable to other children who received a CI. PMID- 24232063 TI - Enlarged cochlear aqueducts: a potential route for CSF gushers in patients with enlarged vestibular aqueducts. AB - OBJECTIVE: We investigated whether the size of the cochlear aqueduct (CA) is increased in patients with enlarged vestibular aqueducts (EVAs) compared with individuals with normal inner ear anatomy. Furthermore, we assessed whether the size of the CA is related to the cerebrospinal fluid (CSF) gusher during cochlear implantation (CI) surgery. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: The medical records for 35 patients with a biallelic SLC26A4 mutation were reviewed. All of the patients were confirmed to have EVA by temporal bone computed tomography (TBCT) and biallelic SLC26A4 mutation by genetic analysis. Thirty-six age- and sex-matched patients without a mutation in the SLC26A4 gene were selected as comparison group. MAIN OUTCOME MEASURES: The diameters of the CA and vestibular aqueduct (VA) were measured, and the type of CA was evaluated using TBCT. RESULTS: The CA was larger in patients with EVA (2.39 +/- 0.99 mm) as compared with controls (1.76 +/- 0.87 mm; p < 0.001). The types that could be most easily visualized from the subarachnoid space to the cochlea were more common in patients with EVA. Furthermore, mean CA size was significantly larger in EVA patients with CSF gushers (3.65 +/- 1.12 mm) as compared with those without CSF gushers (2.03 +/- 0.66 mm; p < 0.001). CONCLUSION: The CA is a potential pathway for CSF gushers between the subarachnoid space and the inner ear. Therefore, we suggest that evaluation of the CA by TBCT may be helpful in predicting intraoperative CSF gushers in patients with EVA. PMID- 24232064 TI - Cochlear implant failure, revision, and reimplantation. AB - OBJECTIVE: To evaluate the long-term adverse cochlear implant (CI) outcomes resulting in revision surgery including CI reimplantation (CIR). PATIENTS: Pediatric and adult patients requiring revision procedures after CI placement. INTERVENTION(S): Revision surgery on cochlear implant patients. MAIN OUTCOME MEASURES: Device type, length of total device follow-up, time to device failure, cause for failure, peak pre-CIR and post-CIR audiometric performance, rate of surgical site complications, and operative findings. RESULTS: A total of 317 patients, receiving 439 CIs between January 2000 and April 2012, met inclusion criteria for this series. For the patients implanted at our institution, the revision surgery rate was 4.1%, with a CIR rate of 3.0%. The CIR rates among the pediatric and adult populations were 5.0% and 1.3%, respectively (p = 0.0336). The rate of revision procedures because of failed fixation or device extrusion was 0.9%. Device failure was experienced in 8 patients in our series, with 75% occurring with the CI24R (CS) device. CONCLUSION: All reimplanted patients with available data had good audiometric outcomes, with the exception of those reimplanted for soft failure who had poor immediate auditory function. Using the manufacturers' recommended surgical technique, including drilling a bony recess with suture fixation, very low surgical revision rates were achieved. Pediatric patients experienced significantly higher complications requiring CIR. All hard failures in this series occurred in the pediatric group and in a single device. Continued follow-up will be needed to determine if additional devices will succumb to this mode of failure. PMID- 24232065 TI - Analysis of intersubject variations in intracochlear and middle ear surface anatomy for cochlear implantation. AB - HYPOTHESIS: We hypothesize that surface landmarks surrounding the round window typically used to guide electrode placement during cochlear implantation (CI) exhibit substantial variability with respect to intracochlear anatomy. BACKGROUND: Recent publications suggest that both atraumatic electrode insertion and electrode location within the scala tympani can affect auditory performance after CI. However, current techniques for electrode insertion rely on surface landmarks alone for navigation, without actual visualization of intracochlear structures other than what can be seen through a surgically created cochleostomy. In this study, we quantify how well the position of intracochlear anatomy is predicted by surface landmarks surrounding the round window. METHODS: Structures representing middle ear surface and intracochlear anatomy were reconstructed in MUCT scans of 10 temporal bone specimens. These structures were then reoriented into a normalized coordinate system to facilitate measurement of inter-subject anatomical shape variations. RESULTS: Only minor intersubject variations were detected for intracochlear anatomy (maximum deviation, 0.71 mm; standard deviation, 0.21 mm), with greatest differences existing near the hook and apex. Larger intersubject variations in intracochlear structures were detected when considered relative to surface landmarks surrounding the round window (maximum deviation, 0.83 mm; standard deviation, 0.54 mm). CONCLUSION: The cochlea and its scala exhibit considerable variability in relation to middle ear surface landmarks. While support for more precise, atraumatic CI electrode insertion techniques is growing in the otologic community, landmark guided insertion techniques have limited precision. Refining the CI insertion process may require the development of image-guidance systems for use in otologic surgery. PMID- 24232066 TI - Outcomes after cochlear implantation for patients with single-sided deafness, including those with recalcitrant Meniere's disease. AB - OBJECTIVE: Compare preoperative and postoperative performance in patients undergoing cochlear implantation (CI) for unilateral severe-to-profound sensorineural hearing loss (single-sided deafness, SSD). STUDY DESIGN: IRB approved, prospective SETTING: Tertiary center PATIENTS: Twenty-nine patients have undergone CI for SSD. SSD was due to Meniere's disease (MD) in 10 subjects; these also suffered from recalcitrant vertigo spells and in these 10 patients along with 2 others the CI was placed simultaneous with a labyrinthectomy. INTERVENTION(S): CI with or without labyrinthectomy. MAIN OUTCOME MEASURE(S): CNC word and AzBio sentences in quiet were administered to the implanted ear. A multiple-loudspeaker sound localization test was administered in the bilateral listening condition. All data were collected preoperatively and 3, 6, and 12 months postoperatively with postoperative data available for 19 subjects. Additionally, a tinnitus handicap questionnaire is administered pre- and 12 months post-operatively. RESULTS: CNC word and AzBio sentence scores showed improvement in the implanted ear. Sound localization appeared to improve in an experience-dependent fashion in some patients. Most patients reported diminished tinnitus after cochlear implantation. All patients undergoing labyrinthectomy experienced resolution of vertigo attacks. CONCLUSION: CI restores auditory function to the deafened ear. Additionally, the binaural input appears to improve sound localization for most patients. In patients with severe hearing loss and recalcitrant vertigo attacks because of MD, simultaneous labyrinthectomy and CI effectively relieves vertigo attacks and improves auditory function. PMID- 24232067 TI - Do audiologic characteristics predict outcomes in children with unilateral hearing loss? AB - OBJECTIVE: To determine whether audiologic characteristics of unilateral hearing loss in children were associated with language, cognitive, or achievement scores. STUDY DESIGN: Case-control study SETTING: Pediatric otolaryngology ambulatory practice PATIENTS: Cases (n = 109) were children aged 6 to 12 years with permanent unilateral hearing loss; controls (n = 95) were siblings with normal bilateral hearing. INTERVENTIONS: Audiologic characteristics measured included side and severity of hearing loss and word recognition scores in quiet and in noise. MAIN OUTCOME MEASURES: Cognitive abilities were measured using the Wechsler Abbreviated Scale of Intelligence; reading, math, and writing achievement was measured with the Wechsler Individual Achievement Test - Second Edition - Abbreviated; and oral language skills were measured with the Oral Written and Language Scales. RESULTS: Children with unilateral hearing loss had worse verbal cognitive and oral language scores than children with normal hearing, but there were no differences in achievement scores. Children with profound unilateral hearing loss tended to have worse cognitive scores and had significantly lower oral language scores. Higher word recognition scores of the normal hearing ear in quiet were associated with higher cognitive, oral language, and reading achievement scores. Higher word recognition scores in noise were slightly correlated with higher oral language scores. CONCLUSION: As expected, children with unilateral hearing loss had worse language scores than their siblings with normal hearing, with trends toward worse cognitive scores. Children with profound unilateral hearing loss tended to have worse outcomes than children with normal hearing or less severe unilateral loss. However, there were no differences in outcomes between children with right or left unilateral hearing loss. PMID- 24232068 TI - First clinical experiences with a direct acoustic cochlear stimulator in comparison to preoperative fitted conventional hearing aids. AB - OBJECTIVE: Patients with moderate-to-severe mixed hearing losses (MHLs) are hard to provide sufficient benefit with currently available conventional hearing aids. Here, the long-term safety of a direct acoustic cochlear stimulator (DACS) and the effectiveness compared with conventional "high-performance" hearing aids were investigated. STUDY DESIGN: Prospective, within patient reference, nonrandomized, interventional multicenter clinical study performed at these 3 centers: Medical University Hannover, University of Heidelberg, and Helios Hospital Krefeld. PATIENTS AND INTERVENTION: Ten otosclerosis patients with severe-to-profound MHL were preoperatively fitted with state-of-the-art conventional hearing aids (HA). After 2 months of testing conventional HA, 9 of the patients decided to be implanted with a DACS. MAIN OUTCOME MEASURES: Air conduction (AC) and bone conduction (BC) aided and unaided thresholds, speech discrimination before and after implantation and at 3, 6, and 12 months after activation. The subjective benefit was assessed by the Abbreviated Profile of Hearing Aid Benefit (APHAB). RESULTS: Preoperative hearing thresholds were preserved over the 12 month observation time after activation. Average functional gain (0.5-4 kHz) achieved with conventional HA was 47 dB compared with 56 dB with the DACS. Speech-in-noise tests revealed a lower SNR for DACS (3.1 dB) than for the HA (6.6 dB) and patients were more satisfied with the DACS. CONCLUSION: The DACS significantly improved hearing, speech intelligibility, and satisfaction in patients with a severe-to-profound mixed hearing loss and can be considered a safe and useful alternative to conventional hearing aids. PMID- 24232069 TI - Neurotologic skull base access for primary tumors of the temporomandibular joint. AB - OBJECTIVES: To familiarize the physician with the clinical and radiographic features associated with primary tumors of the temporomandibular joint (TMJ) and to demonstrate the use of the neurotologic skull base techniques in the surgical extirpation of TMJ tumors. STUDY DESIGN: This was a retrospective chart review spanning the years 1988 to 2012. SETTING: Tertiary care academic medical center. PATIENTS: Any patient with diagnosis of a primary TMJ tumor who received surgical management at our institution. INTERVENTION: The surgical approaches used included preauricular infratemporal fossa, postauricular infratemporal fossa, and pterional infratemporal fossa. MAIN OUTCOME MEASURES: The most critical assessment measures were postoperative patient morbidity and evidence of disease at follow-up visits. RESULTS: The surgical approach was tailored according to the radiographic mapping of the size and location of the tumor. Trismus and jaw discomfort were the most common postoperative complications. Conductive hearing loss occurred only in patients who underwent oversewing of the cartilaginous ear canal. CONCLUSION: The presenting signs and symptoms of extremely rare primary TMJ tumors are those often seen by otolaryngologists. Contemporary neurotologic skull base surgical techniques can optimize the successful extirpation of these lesions. PMID- 24232070 TI - Cerebellopontine angle lymphoma. PMID- 24232071 TI - Important drug-drug interactions for treatments that target overactive bladder syndrome. AB - INTRODUCTION AND HYPOTHESIS: Overactive bladder (OAB) is the term used to describe the symptom complex of urinary urgency,usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology. It is a common distressing condition that significantly impairs quality of life(QoL). After lifestyle advice and bladder retraining,antimuscarinic drugs are most commonly used to treat OAB. METHODS: The antimuscarinics in common use are all metabolised through differing mechanisms. Therefore, the risk of an enhanced drug effect is increased when the potentially interacting substrates compete for the same metabolic pathways. The aim of this review is to provide an overview on potential drug-drug interactions with special emphasis on high-risk groups and clinically important consequences of these interactions RESULTS AND CONCLUSION: Knowledge of current important drug interactions is vital whilst prescribing antimuscarinics, particularly in high risk groups. Novel therapies, such as beta 3 agonists or alternative drug delivery systems, such as the oxybutynin vaginal ring, might provide alternative options where these interactions are unavoidable. PMID- 24232072 TI - Intracranial bleeding following induction of anesthesia in a patient undergoing elective surgery for refractory epilepsy. AB - BACKGROUND: A patient with refractory epilepsy due to underlying mesial temporal sclerosis underwent general anesthesia for an elective anterior temporal lobectomy and amgydalo-hippocampectomy. He was a known hypertensive and his blood pressure was well controlled on medication. CASE DESCRIPTION: Following induction of general anesthesia and subsequent opening of the craniotomy flap it was noted that the patient had a very swollen brain that herniated out of the dural defect. There was an underlying spontaneous intraparenchymal bleed encountered in the region of the left temporal lobe with associated subarachnoid hemorrhage within the sylvian fissure. The clot was evacuated and subsequently brain swelling reduced allowing us to proceed with the intended surgery. Despite the intracranial findings there was no overt abnormality in the hemodynamic status from the time of induction of anesthesia to the craniotomy opening excepting a mild nonsustained elevation of blood pressure at the outset. CONCLUSION: This case is of interest due to the fact that spontaneous intraparenchymal bleeding after induction of anesthesia has not been reported before in literature and should be considered in any patient in which brain swelling occurs in a setting of elective neurosurgery in which the primary lesion does not cause elevated intracranial pressure. PMID- 24232074 TI - The use of handheld near-infrared device (Infrascanner) for detecting intracranial haemorrhages in children with minor head injury. AB - OBJECTIVE: A handheld device using near-infrared technology (Infrascanner) has shown good accuracy for detection of traumatic intracranial haemorrhages in adults. This study aims to determine the feasibility of use of Infrascanner in children with minor head injury (MHI) in the Emergency Department (ED). Secondary aim was to assess its potential usefulness to reduce CT scan rate. METHODS: Prospective pilot study conducted in two paediatric EDs, including children at high or intermediate risk for clinically important traumatic brain injury (ciTBI) according to the adapted PECARN rule in use. Completion of Infrascanner measurements and time to completion were recorded. Decision on CT scan and CT scan reporting were performed independently and blinded to Infrascanner results. RESULTS: Completion of the Infrascanner measurement was successfully achieved in 103 (94 %) of 110 patients enrolled, after a mean of 4.4 +/- 2.9 min. A CT scan was performed in 18 (17.5 %) children. Only one had an intracranial haemorrhage that was correctly identified by the Infrascanner. The exploratory analysis showed a specificity of 93 % (95 % CI, 86.5-96.6) and a negative predictive value of 100 % (95 % CI, 81.6-100) for ciTBI. The use of Infrascanner would have led to avoid ten CT scan, reducing the CT scan rate by 58.8 %. CONCLUSIONS: Infrascanner seems an easy-to-use tool for children presenting to the ED following a MHI, given the high completion rate and short time to completion. Our preliminary results suggest that Infrascanner is worthy of further investigation as a potential tool to decrease the CT scan rate in children with MHI. PMID- 24232075 TI - Navigation lymphatic supermicrosurgery for the treatment of cancer-related peripheral lymphedema. AB - BACKGROUND: Lymphatic supermicrosurgery is becoming the treatment of choice for refractory lymphedema. Detection and anastomosis of functional lymphatic vessels are important for lymphatic supermicrosurgery. METHODS: Navigation lymphatic supermicrosurgery was performed using an operating microscope equipped with an integrated near-infrared illumination system (OPMI Pentero Infrared 800; Carl Zeiss, Oberkochen, Germany). Eight patients with extremity lymphedema who underwent navigation lymphatic supermicrosurgery were evaluated. RESULTS: A total of 21 lymphaticovenular anastomoses were performed on 8 limbs through 14 skin incisions. Lymphatic vessels were enhanced by intraoperative microscopic indocyanine green (ICG) lymphography in 12 of the 14 skin incisions, which resulted in early dissection of lymphatic vessels. All anastomoses showed good anastomosis patency after completion of anastomoses. Postoperative extremity lymphedema index decreased in all limbs. CONCLUSIONS: Navigation lymphatic supermicrosurgery, in which lymphatic vessels are visualized with intraoperative microscopic ICG lymphography, allows a lymphatic supermicrosurgeon to find and dissect lymphatic vessels earlier and facilitates successful performance of lymphaticovenular anastomosis. PMID- 24232076 TI - Metal MEMS Tools for Beating-heart Tissue Removal. AB - A novel robotic tool is proposed to enable the surgical removal of tissue from inside the beating heart. The tool is manufactured using a unique metal MEMS process that provides the means to fabricate fully assembled devices that incorporate micron-scale features in a millimeter scale tool. The tool is integrated with a steerable curved concentric tube robot that can enter the heart through the vasculature. Incorporating both irrigation and aspiration, the tissue removal system is capable of extracting substantial amounts of tissue under teleoperated control by first morselizing it and then transporting the debris out of the heart through the lumen of the robot. Tool design and robotic integration are described and ex vivo experimental results are presented. PMID- 24232077 TI - Formulation and evaluation of liquisolid compacts for olmesartan medoxomil. AB - Olmesartan medoxomil is an angiotensin type II receptor blocker, antihypertensive agent, administered orally. It is highly lipophilic (log P 5.5) and a poorly water-soluble drug with absolute bioavailability of 26%. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. The objective of the present investigation was to develop liquisolid compacts for olmesartan medoxomil to improve the dissolution rate. Liquisolid compacts were prepared using Acrysol El 135 as a solvent, Avicel PH 102, Fujicalin and Neusilin as carrier materials, and Aerosil as coating material in different ratios. The interaction between drug and excipients was characterized by DSC and FT-IR studies, which showed that there is no interaction between drug and excipients. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial limits. The dissolution studies for liquisolid compacts and conventional formulations were carried out, and it was found that liquisolid compacts with 80% w/w of Acrysol EL 135 to the drug showed significant higher drug release rates than conventional tablets. Amongst carriers used Fujicalin and Neusilin were found to be more effective carrier materials for liquid adsorption. PMID- 24232078 TI - Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint. AB - IMPORTANCE: The study demonstrates use of a novel intervention for severe tracheobronchomalacia (TBM). OBJECTIVE: To test a novel, 3-dimensionally (3D) printed, bioresorbable airway splint for efficacy in extending survival in a porcine model of severe, life-threatening TBM. DESIGN AND PARTICIPANTS: A randomized, prospective animal trial was used to evaluate an external airway splint as treatment of severe, life-threatening TBM in a multi-institutional, multidisciplinary collaboration between a biomedical engineering department and an academic animal surgery center. Six 2-month-old Yorkshire pigs underwent tracheal cartilage division and inner tracheal lumen dissociation and were randomly assigned to splint treatment (n = 3) or control groups (n = 3). Two additional pigs had the splint placed over their normal trachea. INTERVENTIONS: A 3D-printed, bioresorbable airway splint was assessed in a porcine animal model of life-threatening TBM. The open-cylindrical, bellow-shaped, porous polycaprolactone splint was placed externally and designed to suspend the underlying collapsed airway. Two additional animals were splinted without model creation. MAIN OUTCOMES AND MEASURES: The observer-based Westley Clinical Croup Scale was used to assess the clinical condition of animals postoperatively. Animal survival time was noted. RESULTS: Complete or nearly complete tracheal lumen collapse was observed in each animal, with resolution of symptoms in all of the experimental animals after splint placement. Using our severe TBM animal model, survival was significantly longer in the experimental group receiving the airway splint after model creation than in the control group (P = .0495). CONCLUSIONS AND RELEVANCE: A multidisciplinary effort producing a computer-aided designed, computer-aided manufactured bioresorbable tracheobronchial splint was tested in a porcine model of severe TBM and was found to extend survival time. Mortality in the splinted group was ascribed to the TBM model based on the lack of respiratory distress in splinted pigs, long-term survival in animals implanted with the splint without TBM, and necropsy findings. PMID- 24232081 TI - Multiple pigmented basal cell carcinomas of the eyelids. PMID- 24232082 TI - Dehisced corneal button with no evidence of a ruptured globe. PMID- 24232083 TI - Stromal duplication of the iris. PMID- 24232084 TI - Surgery, pathology, and art in Pietro Gradenigo's ophthalmologic waxworks. AB - Pietro Gradenigo (1831-1904) represents one of the greatest eras of cultural and scientific activity in Italian ophthalmology. Padua's Vincenzo Pinali Medico historical Library preserves 2 series of ophthalmologic wax models. Made by Pietro Gradenigo in 1884-1889, the first consists of 18 waxes and shows different eyes diseases, such as neoplasm and tenonitis, and ophthalmologic surgical operations, such as some interesting cases of blepharoplasty. The second series from Vienna Medical School was created by Johann Hofmayer, ophthalmologist of the Josephinum in Vienna. The ideas at the foundation of wax modeling and operations represented in these series have some original and significant implications related to the role of medical imaging in didactic and research. PMID- 24232085 TI - More than just optic disc swelling. PMID- 24232086 TI - Fundus autofluorescence is not the best early screen for hydroxychloroquine toxicity. PMID- 24232087 TI - Amyloid deposits in temporal artery mimicking temporal arteritis in a patient with multiple myeloma. PMID- 24232088 TI - Fundus autofluorescence is not the best early screen for hydroxychloroquine toxicity--reply. PMID- 24232090 TI - Delayed-onset inferior rectus muscle hematoma after orbital floor fracture. PMID- 24232092 TI - CD40-directed scFv-TRAIL fusion proteins induce CD40-restricted tumor cell death and activate dendritic cells. AB - Targeted cancer therapy concepts often aim at the induction of adjuvant antitumor immunity or stimulation of tumor cell apoptosis. There is further evidence that combined application of immune stimulating and tumor apoptosis-inducing compounds elicits a synergistic antitumor effect. Here, we describe the development and characterization of bifunctional fusion proteins consisting of a single-chain variable fragment (scFv) domain derived from the CD40-specific monoclonal antibody G28-5 that is fused to the N-terminus of stabilized trimeric soluble variants of the death ligand TNF-related apoptosis-inducing ligand (TRAIL). As shown before by us and others for other cell surface antigen-targeted scFv-TRAIL fusion proteins, scFv:G28-TRAIL displayed an enhanced capacity to induce apoptosis upon CD40 binding. Studies with scFv:G28 fusion proteins of TRAIL mutants that discriminate between the two TRAIL death receptors, TRAILR1 and TRAILR2, further revealed that the CD40 binding-dependent mode of apoptosis induction of scFv:G28-TRAIL is operable with each of the two TRAIL death receptors. Binding of scFv:G28-TRAIL fusion proteins to CD40 not only result in enhanced TRAIL death receptor signaling but also in activation of the targeted CD40 molecule. In accordance with the latter, the scFv:G28-TRAIL fusion proteins triggered strong CD40-mediated maturation of dendritic cells. The CD40-targeted TRAIL fusion proteins described in this study therefore represent a novel type of bifunctional fusion proteins that couple stimulation of antigen presenting cells and apoptosis induction. PMID- 24232093 TI - Measurement of autophagy flux in the nervous system in vivo. AB - Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings. PMID- 24232094 TI - A set of microRNAs mediate direct conversion of human umbilical cord lining derived mesenchymal stem cells into hepatocytes. AB - In a previous study, we elucidated the specific microRNA (miRNA) profile of hepatic differentiation. In this study, we aimed to clarify the instructive role of six overexpressed miRNAs (miR-1246, miR-1290, miR-148a, miR-30a, miR-424 and miR-542-5p) during hepatic differentiation of human umbilical cord lining-derived mesenchymal stem cells (hMSCs) and to test whether overexpression of any of these miRNAs is sufficient to induce differentiation of the hMSCs into hepatocyte-like cells. Before hepatic differentiation, hMSCs were infected with a lentivirus containing a miRNA inhibitor sequence. We found that downregulation of any one of the six hepatic differentiation-specific miRNAs can inhibit HGF-induced hepatic differentiation including albumin expression and LDL uptake. Although overexpression of any one of the six miRNAs alone or liver-enriched miR-122 cannot initiate hepatic differentiation, ectopic overexpression of seven miRNAs (miR-1246, miR-1290, miR-148a, miR-30a, miR-424, miR-542-5p and miR-122) together can stimulate hMSC conversion into functionally mature induced hepatocytes (iHep). Additionally, after transplantation of the iHep cells into mice with CCL4 induced liver injury, we found that iHep not only can improve liver function but it also can restore injured livers. The findings from this study indicate that miRNAs have the capability of directly converting hMSCs to a hepatocyte phenotype in vitro. PMID- 24232095 TI - (ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease. AB - Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson's disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration. PMID- 24232096 TI - Smac mimetics induce inflammation and necrotic tumour cell death by modulating macrophage activity. AB - Smac mimetics (SMs) comprise a class of small molecules that target members of the inhibitor of apoptosis family of pro-survival proteins, whose expression in cancer cells hinders the action of conventional chemotherapeutics. Herein, we describe the activity of SM83, a newly synthesised dimeric SM, in two cancer ascites models: athymic nude mice injected intraperitoneally with IGROV-1 human ovarian carcinoma cells and immunocompetent BALB/c mice injected with murine Meth A sarcoma cells. SM83 rapidly killed ascitic IGROV-1 and Meth A cells in vivo (prolonging mouse survival), but was ineffective against the same cells in vitro. IGROV-1 cells in nude mice were killed within the ascites by a non-apoptotic, tumour necrosis factor (TNF)-dependent mechanism. SM83 administration triggered a rapid inflammatory event characterised by host secretion of TNF, interleukin 1beta and interferon-gamma. This inflammatory response was associated with the reversion of the phenotype of tumour-associated macrophages from a pro-tumoural M2- to a pro-inflammatory M1-like state. SM83 treatment was also associated with a massive recruitment of neutrophils that, however, was not essential for the antitumoural activity of this compound. In BALB/c mice bearing Meth A ascites, SM83 treatment was in some cases curative, and these mice became resistant to a second injection of cancer cells, suggesting that they had developed an adaptive immune response. Altogether, these results indicate that, in vivo, SM83 modulates the immune system within the tumour microenvironment and, through its pro inflammatory action, leads cancer cells to die by necrosis with the release of high-mobility group box-1. In conclusion, our work provides evidence that SMs could be more therapeutically active than expected by stimulating the immune system. PMID- 24232097 TI - Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis. AB - Oxidative stress and reactive oxygen species (ROS) are associated with diseases such as cancer, cardiovascular complications, inflammation and neurodegeneration. Cellular defense systems must work constantly to control ROS levels and to prevent their accumulation. We report here that the Jun dimerization protein 2 (JDP2) has a critical role as a cofactor for transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and small Maf protein family K (MafK) in the regulation of the antioxidant-responsive element (ARE) and production of ROS. Chromatin immunoprecipitation-quantitative PCR (qPCR), electrophoresis mobility shift and ARE-driven reporter assays were carried out to examine the role of JDP2 in ROS production. JDP2 bound directly to the ARE core sequence, associated with Nrf2 and MafK (Nrf2-MafK) via basic leucine zipper domains, and increased DNA binding activity of the Nrf2-MafK complex to the ARE and the transcription of ARE dependent genes. In mouse embryonic fibroblasts from Jdp2-knockout (Jdp2 KO) mice, the coordinate transcriptional activation of several ARE-containing genes and the ability of Nrf2 to activate expression of target genes were impaired. Moreover, intracellular accumulation of ROS and increased thickness of the epidermis were detected in Jdp2 KO mice in response to oxidative stress-inducing reagents. These data suggest that JDP2 is required to protect against intracellular oxidation, ROS activation and DNA oxidation. qPCR demonstrated that several Nrf2 target genes such as heme oxygenase-1, glutamate-cysteine ligase catalytic and modifier subunits, the notch receptor ligand jagged 1 and NAD(P)H dehydrogenase quinone 1 are also dependent on JDP2 for full expression. Taken together, these results suggest that JDP2 is an integral component of the Nrf2 MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE. PMID- 24232098 TI - miR-24 affects hair follicle morphogenesis targeting Tcf-3. AB - During embryonic development, hair follicles (HFs) develop from an epidermal mesenchymal cross talk between the ectoderm progenitor layer and the underlying dermis. Epidermal stem cell activation represents a crucial point both for HF morphogenesis and for hair regeneration. miR-24 is an anti-proliferative microRNA (miRNA), which is induced during differentiation of several cellular systems including the epidermis. Here, we show that miR-24 is expressed in the HF and has a role in hair morphogenesis. We generated transgenic mice ectopically expressing miR-24 under the K5 promoter. The K5::miR-24 animals display a marked defect in HF morphogenesis, with thinning of hair coat and altered HF structure. Expression of miR-24 alters the normal process of hair keratinocyte differentiation, leading to altered expression of differentiation markers. MiR-24 directly represses the hair keratinocyte stemness regulator Tcf-3. These results support the notion that microRNAs, and among them miR-24, have an important role in postnatal epidermal homeostasis. PMID- 24232100 TI - Inheritance and structure of foreign DNA in progenies of transgenic tobacco obtained by direct gene transfer. AB - One of the transformed tobacco plants obtained by direct DNA transformation possessed two marker genes, a chimeric aminoglycoside phosphotransferase and nopaline synthase genes. Selfed progenies of this plant (T3-d) showed stable inheritance of these two genes. The minimum size of foreign DNA integrated into tobacco genome was estimated to be 5.4 kbp. A deleted nopaline synthase gene co existed with an intact gene. The linkage analysis indicated that two transformants, T1-b and T3-c, possessed foreign DNA inserted in different chromosomes or in different sites of the same chromosome that recombine freely. PMID- 24232099 TI - FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway. AB - The fucosyltransferase (FUT) family is the key enzymes in cell-surface antigen synthesis during various biological processes such as tumor multidrug resistance (MDR). The aim of this work was to analyze the alteration of FUTs involved in MDR in human hepatocellular carcinoma (HCC) cell lines. Using mass spectrometry (MS) analysis, the composition profiling of fucosylated N-glycans differed between drug-resistant BEL7402/5-FU (BEL/FU) cells and the sensitive line BEL7402. Further analysis of the expressional profiles of the FUT family in three pairs of parental and chemoresistant human HCC cell lines showed that FUT4, FUT6 and FUT8 were predominant expressed in MDR cell lines. The altered levels of FUT4, FUT6 and FUT8 were responsible for changed drug-resistant phenotypes of BEL7402 and BEL/FU cells both in vitro and in vivo. In addition, regulating FUT4, FUT6 or FUT8 expression markedly modulated the activity of the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway and MDR-related protein 1 (MRP1) expression. Inhibition of the PI3K/Akt pathway by its specific inhibitor wortmannin, or by Akt small interfering RNA (siRNA), resulted in decreased MDR of BEL/FU cells, partly through the downregulation of MRP1. Taken together, our results suggest that FUT4-, FUT6- or FUT8-mediated MDR in human HCC is associated with the activation of the PI3K/Akt pathway and the expression of MRP1, but not of P-gp, indicating a possible novel mechanism by which the FUT family regulates MDR in human HCC. PMID- 24232101 TI - Transfer and segregation of triazine tolerant chloroplasts in Brassica napus L. AB - Hypocotyl protoplasts of 45 different genotypes of German winter oilseed rape Brassica napus L. (double zero quality: high in yield, seeds low in erucic acid and glucosinolate content) were regenerated to plants. Triazine/triazinone (tri) tolerant chloroplasts of the Canadian spring oilseed rape variety OAC Triton were introduced into some winter oilseed rapes by means of protoplast fusion. X-ray irradiation was used to limit the transfer of nuclear DNA of Triton protoplasts and to promote the selective transfer of tri-tolerant chloroplasts. Regenerated "cybrid" plants survived a treatment rate of 1000 g/ha metribuzin. The presence and segregation of the tri-tolerant chloroplasts in winter oilseed rape plants, regenerated from fusion products and their progeny, was investigated by restriction fragment length polymorphism (RFLP). Our results indicate that chloroplast segregation was not completed in plants regnerated from fusion products derived from X-irradiated OAC Triton mesophyll protoplasts and German winter oilseed rape hypocotyl protoplasts. In regenerants and their progeny both chloroplast types can still be present. Chloroplasts derived from wintertype protoplasts can outcompete tritolerant chloroplasts during plant development. In some instances, even progeny plants not kept under selective conditions (metribuzin) lost tri-tolerant chloroplasts. A homogenous population of tri tolerant chloroplasts was necessary to obtain stable tri-tolerant winter oilseed rape plants. PMID- 24232102 TI - The origin of the cultivated tetraploid potato based on chloroplast DNA. AB - By using restriction enzyme analysis of chloroplast DNA, a geographical cline from the Andean region to coastal Chile was found for the tetraploid potato (Solanum tuberosum). This supports the Andean origin of Chilean ssp. tuberosum. One of the relic cultivars of the early introduction of potato to Europe had ssp. andigena type chloroplast DNA. Its derivatives were largely lost in the mid-19th century due to the late blight epidemic and were replaced by ssp. tuberosum originally introduced from Chile. Therefore, the present common potato has the same type chloroplast DNA as Chilean ssp. tuberosum. PMID- 24232103 TI - A second mutation enhances resistance of a tobacco mutant to sulfonylurea herbicides. AB - Cultures of Nicotiana tabacum cells homozgous for a mutation (S4) at the SuRB locus that confers resistance to the sulfonylurea herbicides chlorsulfuron and sulfometuron methyl (Chaleff and Ray 1984; Chaleff and Bascomb 1987) were used to isolate a doubly mutant cell line (S4 Hra/S4+) resistant to even higher herbicide concentrations. Growth of cells homozygous for both the S4 and Hra mutations (S4 Hra/S4 Hra) was uninhibited by a herbicide concentration 500-fold higher than a concentration by which growth of S4+/S4+ callus was inhibited by 75%. Plants homozygous for both mutations were at least five-fold more resistant to foliar applications of chlorsulfuron than were singly mutant S4+/S4+ plants. This enhanced resistance was inherited as a single, semidominant, nuclear trait that is genetically linked to the S4 mutation. Acetolactate synthase (ALS) activity in extracts of leaves of doubly mutant (S4 Hra/S4 Hra) plants was approximately 20 fold more resistant to inhibition by chlorsulfuron and sulfometuron methyl than was ALS activity in singly mutant (S4+/ S4+) leaf extracts, which was in turn more resistant to inhibition by these compounds than was the normal enzyme. Extracts prepared from plants of these three genotypes possessed the same ALS specific activities. Therefore, Hra represents a second independent mutation at or near the SuRB locus that reduces the sensitivity of tobacco ALS activity to inhibition by sulfonylurea herbicides. PMID- 24232104 TI - Chromosomal location of genes conditioning low amylose content of endosperm starches in rice, Oryza sativa L. AB - Eight dull mutants that lower the amylose content of rice endosperm as well as waxy mutant and a cultivar with common grains were crossed in a diallele manner. The amylose content of F1 and F2 seeds was determined on the basis of single grain analysis. It was concluded that the low amylose content of dull mutants is under monogenic recessive control. Alleles for low amylose content are located at five loci designated as du-1, du-2, du-3, du-4 and du-5. These loci are independent of wx locus located on chromosome 6. The five du loci have an additive effect in lowering the amylose content. Two loci, du-1 and du-4, were found to be located on chromosomes 7 and 4, respectively. PMID- 24232105 TI - Outcrossing rates and male sterility in natural populations of Plantago coronopus. AB - Outcrossing rates were estimated in three populations of the gynodioecious species Plantago coronopus by means of electrophoresis of adult plants and their natural progenies. A multilocus estimation procedure was used. Heterogeneity among the pollen-pool allele frequencies did not exist either in space of in time. Differences between populations in mean outcrossing rates were large (range: 0.34-0.93), probably caused by differences in densities of flowering plants. In addition, there was considerable variability between individuals, which was at least partly caused by the presence of male sterility. Population density may, via its influence on outcrossing rates, be a factor influencing the maintenance of male sterile plants in the population. The level of outcrossing in hermaphrodites was not low enough to explain the maintenance of male steriles. Outcrossing rates in two populations, established via progeny analysis, were much lower than calculated with the fixation index, possibly indicating heterozygote advantage in these natural populations. PMID- 24232106 TI - Diploid Brassica napus somatic hybrids: characterization of nuclear and organellar DNA. AB - Five somatic hybrids between Brassica campestris and B. oleracea were obtained. Molecular, morphological and cytological information all suggest that the resynthesized B. napus plants were hybrids. All five plants were diploid (2n=38) and had mainly bivalents at meiosis. Seedset was low after selfing but normal after crossing with B. napus. Molecular proof of the hybrid nature of these plants was obtained by hybridization of a rDNA repeat to total DNA. Analysis of chloroplast DNA restriction patterns revealed that all hybrids had chloroplasts identical to the B. oleracea parent. The analysis of mitochondrial DNA indicated that three hybrids had restriction patterns identical to those of B. campestris, and the other two had restriction patterns similar to those of B. oleracea. The 11.3 kb plasmid present in mitochondria of the B. campestris parent was also found in mitochondria of all five hybrids. This suggests that the plasmid from a B. campestris type of mitochondria was transferred into mitochondria of a B. oleracea type. PMID- 24232107 TI - Effects of Alternaria alternata f.sp. lycopersici toxins on pollen. AB - Effects of the phytotoxic compounds (AAL-toxins) isolated from cell-free culture filtrates of Alternaria alternata f.sp. lycopersici on in vitro pollen development were studied. AAL-toxins inhibited both germination and tube growth of pollen from several Lycopersicon genotypes. Pollen from susceptible genotypes, however, was more sensitive for AAL-toxins than pollen from resistant plants, while pollen of species not belonging to the host range of the fungus was not significantly affected by the tested toxin concentrations. AAL-toxins elicit symptoms in detached leaf bioassays indistinguishable from those observed on leaves of fungal infected tomato plants, and toxins play a major role in the pathogenesis. Apparently, pathogenesis-related processes and mechanisms involved in disease resistance are expressed in both vegetative and generative tissues. This overlap in gene expression between the sporophytic and gametophytic level of a plant may be advantageously utilized in plant breeding programmes. Pollen may be used to distinguish susceptible and resistant plants and to select for resistances and tolerances against phytotoxins and other selective agents. PMID- 24232108 TI - Choice of method for identifying germplasm with superior alleles : 1. Theoretical results. AB - Elite, adapted germplasm is not likely to contain all the favorable alleles available in a species. Three statistics were evaluated for screening populations for their ability to contribute favorable dominant alleles not available in an elite single cross: (1) a statistic proposed by Dudley (SD)=[(P x I1-I1)(I1 x I2 I2)-(P x I2-I2) (I1 x I2-I1)]/[2(I1-I2)]; (2) the upper bound minimum (P x I1-I1, P x I2-I2) ; and (3) the testcross to the single cross [TC(SC)]=P x (I1 x I2), where P is the population to be evaluated and I1 and I2 are homozygous parents of the elite single cross I1*I2. A superiority measure for a population was defined as the product of frequencies of favorable alleles and effects summed over loci where I1*I2 is homozygous unfavorable. Of the statistics considered, TC (SC) should have the highest genetic correlation with the superiority measure under the assumptions made, require the fewest testing resources and have the smallest standard error. Methods considered for screening inbreds were: (1) SDI proposed by Dudley=[(I1 x IW)+(I2 x IW)-I1-I2-IW-(I1 x I2)]/4 ; (2) TC(SC)=IW x (I1 xI2); and (3) UBND=minimum where Iw is the inbred to be evaluated. The superiority measure of an inbred Iw was defined as the relative number of loci where I1 and I2 are unfavorable and Iw is favorable. The genetic correlation with the superiority measure should be highest for SDI. The larger number of measurements used in calculation, the necessity of evaluating potentially unadapted inbreds and larger testing resources required for SDI suggest further research should be done to evaluate these statistics. PMID- 24232109 TI - Choice of method for identifying germplasm with superior alleles : 2. Computer simulation results. AB - An accurate and efficient method of screening the many germplasm sources available for their ability to improve elite, adapted germplasm is needed. The superiority measure (SX) of a population (P) was defined as the product of the frequency and relative superiority of the alleles in P that are more favorable than the best in an elite, adapted reference single cross I1*I2. A computer simulation was done to determine the correlations between various screening methods and the SX. The genetic model used included multiple alleles, no linkage, two types of non-epistatic gene action (additive and complete dominance) and two types of epistatic gene action (complementary and duplicate). Genetic variances in the populations and a statistic proposed by Dudley (SD={[P x I1-I1] [I1 xI2 I2]- [P x I2-I2]-[P x I2-I2] [I1 x I2-I1]}/{2[I1-I2]{) were inconsistently correlated with the SX over all types of gene action on the basis of rank correlations. The testcross to the single cross (TC[SC]=P x [I1 x I2]) and the upper bound on the SX (UBND=minimum [P x I1-I1, P x I2-I2]) were both consistently highly genetically correlated with the SX. In the set of populations simulated, there were positive correlations between products of allelic frequencies and effects at different classes of loci. The UBND usually had a higher rank correlation coefficient with the SX than did the TC(SC). The differences between their correlation coefficients were often insignificant. Although the TC(SC) gives no indication as to which inbred the population is more closely related, its ease of use and expected lowers standard error compared with the UBND indicate that it would be an appropriate choice of screening method for identifying superior populations in the sense defined. PMID- 24232110 TI - Detection of linkage between marker loci and loci affecting quantitative traits in crosses between segregating populations. AB - By making use of pedigree information and information on marker-genotypes of the parent and F-1 individuals crossed to form an F-2 population, it is possible to carry out a linkage analysis between marker loci and loci affecting quantitative traits in a cross between segregating parent populations that are at fixation for alternative alleles at the QTL, but share the same alleles at the marker loci. For two-allele systems, depending on marker allele frequencies in the parent populations, 2-4 times as many F-2 offspring will have to be raised and scored for markers and quantitative traits in order to provide power equivalent to that obtained in a cross between fully inbred lines. Major savings in number of F-2 offspring raised can be achieved by scoring each parent pair for a large number of markers in each chromosomal region and scoring F-1 and F-2 offspring only for those markers for which the parents were homozygous for alternative alleles. For multiple allele systems, particularly when dealing with hypervariable loci, only 10%-20% additional F-2 offspring will have to be raised and scored to provide power equivalent to that obtained in a cross between inbred lines. When a resource population contains novel favorable alleles at quantitative trait loci that are not present (or rare) in a commercial population, analyses of this sort will enable the loci of interest to be identified, mapped and manipulated effectively in breeding programs. PMID- 24232111 TI - A selection method for the synthesis of triploid hybrids by fusion of microspore protoplasts (n) with somatic cell protoplasts (2n). AB - Microspore protoplasts (n) isolated at the tetrad stage from plants of Nicotiana tabacum Km(+) (2n=4x=48) were fused with somatic cell protoplasts (2n) of WT N. rustica (2n=4x=48) to produce triploid plants. A total of 21.2*10(6) microspore protoplasts were fused with 11.2*10(6) somatic cell protoplasts using the high pH/Ca(+ +) method. Microspore protoplasts did not divide and WT N. rustica protoplasts stopped dividing when the protoplast-derived colonies were transferred to a selection medium containing kanamycin. A total of 104 actively growing green colonies were recovered on the selection medium. Ninety-six of these colonies were tested for their hybrid nature by PAGE of peroxidases and were found to contain bands characteristic of both parents. Hybrid nature of the plants regenerated from some of the selected colonies was confirmed by IEF of leaf esterases, by NPT II activity assay and by hybridizing total DNAs restricted with EcoR I to a cloned 18s rDNA fragment. Root tip squashes of six of the hybrid plants revealed chromosome numbers ranging from 58-72. From chromosomal and biochemical analysis, it can be concluded that the procedure of fusing microspore protoplasts (n) of species A carrying a dominant selection marker with WT somatic cell protoplasts (2n) of species B can be a convenient selection method for the synthesis of triploid plants. The significance of triploids lies in their subsequent use for transferring alien chromosomes and genes of species A to species B. PMID- 24232112 TI - Comparisons of zein profiles from inbred, F1, and F 2 generations of maize as revealed by reversed-phase high-performance liquid chromatography. AB - Chi-square analyses were performed on zein Chromatographic profiles of inbred lines, F1, F2, and reciprocal F1 seed for 10 hybrids of maize (Zea mays L.). The objective was to test the goodness of fit of observed profiles with those expected on the basis that the F1 and F2 generations represent a 2?1 and 1?1 addition of Female?male parents of the F1, respectively. From 40 available comparisons, 39 showed no difference between the observed chromatograms and those that were expected on the basis of four models that were tested. The one exception was due to closely eluting peaks that were revealed as shoulders and not recorded as separate entities. chromatographic profiles of inbreds, F1, and bulk F2 seed sources can be accurately simulated. Even though the chromatographic profile of the F1 closely resembled that of the female parent, profiles of hybrids with common female but different male parents were distinguishable. The lack of novel peaks in both F1 and F2 generations compared with the inbred line thereby revealed no unpredictable interaction among zein loci. Zein protein data can be useful in registration, certification, and in the checking of hybrid pedigree especially when used in concert with isozymic data. PMID- 24232113 TI - Production of F1 and F 2 diploid gynogenetic tilapias and analysis of the "Hertwig curve" obtained using ultraviolet irradiated sperm. AB - In this study, a Hertwig effect with a non-typical biphasic curve was obtained using sperm irradiated with increasing intensities of UV. The first phase of the UV curve appeared to be quite different from that normally demonstrated using gamma or x-ray irradiation. This difference is characterised throughout the length of the first phase by (1) low and stable embryo hatching rates of about 3.5%, and (2) exclusive formation of haploid embryos at any irradiation intensity. Additionally, at both phases, the ability of the sperm to induce morula formation was not affected at all, and no aneuploidy nor chromosomal fragments could be seen. Therefore, it was suggested that in this fish the lethal effect of UV irradition on sperm is mainly expressed on early differentiative events during embryogenesis, which lead to a degeneration of the embryos during early stages of their development. The possible mechanism by which haploidy is achieved during the first phase is discussed. Two generations of diploid gynogenetic tilapias were induced by activating Oreochromis aureus eggs with UV irradiated O. niloticus sperm and by using the heat-shock technique, at optimized conditions, for the prevention of the second polar body extrusion. Species specific dominant genetic markers (serum esterases and tail striation) were used to confirm the exclusive content of the maternal genome in gynogenetic offspring. Very low survival rates (0.36%) were shown in F1 gynogenetic fish as well as a high incidence of malformations among survivors. In the second gynogenetic generation, both significantly higher survival rates (3.6%) and a considerably reduced incidence of malformations were obtained. We suggest that low frequencies of recombination occur in this species and cause a rapid increase in the inbreeding level. This is followed by the expression of lethal and defective genes that are considerably reduced after second generation selection. PMID- 24232114 TI - Production of somatic hybrids by electrofusion in Solanum. AB - Conditions are described for large scale electrofusion of mesophyll protoplasts of dihaploid S. tuberosum with those of diploid S. brevidens. Overall fusion frequencies of 20%-30% were achieved, and following fusion, large numbers of protoplast-derived calli were obtained. Putative somatic hybrid plants were selected from the regenerated shoots by examining their morphological characteristics. Twenty-one somatic hybrids were confirmed by isoenzyme analysis and six somatic hybrids were further confirmed by Southern hybridization. Tetraploid hybrids were obtained, but cytogenetic studies indicated that more of the regenerated hybrids were hexaploid than had previously been found following chemical fusion of the same partners. Some advantages of electrofusion over chemical fusion are discussed. PMID- 24232115 TI - Evaluation of hypotheses concerning the origin of Lotus corniculatus (Fabaceae) using isoenzyme data. AB - An isoenzyme survey was conducted for several geographically dispersed accessions of four diploid Lotus species, L. alpinus Schleich., L. japonicus (Regel) Larsen, L. tenuis Waldst. et Kit and L. uliginosus Schkuhr, and for the tetraploid L. corniculatus L., in order to ascertain whether isoenzyme data could offer additional evidence concerning the origin of L. corniculatus. Seven enzyme systems were examined using horizontal starch gel electrophoresis. These were PGI, TPI, MDH, IDH, PGM, 6-PGDH, and ME. Lotus uliginosus had monomorphic unique alleles, that were not found within L. corniculatus, at 7 loci. These loci and alleles are: Tpi1-112, Pgm1,2-110, Pgm3-82, Mdh3-68, 6-Pgdh1-110, 6-Pgdh2-98,95, and Me2-100. Other diploid taxa contained alleles found in L. corniculatus for these and other loci. The implications of the isoenzyme data to theories on the origin of L. corniculatus are discussed. PMID- 24232116 TI - The genomic relationship between cultivated sorghum [Sorghum bicolor (L.) Moench] and Johnsongrass [S. halepense (L.) Pers.]: a re-evaluation. AB - The genomic relationship between cultivated sorghum [Sorghum bicolar (L.) Moench, race bicolor, De Wet, 2n=20] and Johnsongrass [S. halepense (L.) Pers., 2n=40] has been a subject of extensive studies. Nevertheless, there is no general consensus concerning the ploidy level and the number of genomes present in the two species. This research tested the validity of four major genomic models that have been proposed previously for the two species by studying chromosome behaviors in the parental species, 30-chromosome hybrids [sorghum, (2n=20) x Johnsongrass, (2n=40)], 40-chromosome hybrids [sorghum, (2n=40) x Johnsongrass, (2n=40)] and 60-chromosome amphiploids. Chromosome pairings of amphiploids are reported for the first time. Chromosomes of cultivated sorghums paired exclusively as 10 bivalents, whereas Johnsongrass had a maximum configuration of 5 ring quadrivalents with occasional hexavalents and octovalents. In contrast, 40 chromosome cultivated sorghum had up to 9 ring quadrivalents and 1 hexavalent. Pairing in the 30-chromosome hybrids showed a maximum of 10 trivalents, and that in the 40-chromosome hybrids exhibited 8 quadrivalents, 5 of which were rings, together with a few hexavalents. Amphiploid plants showed up to 3 ring hexavalents, 1 chain hexavalent and a chain of 12 chromosomes. The data suggest that cultivated sorghum is a tetraploid species with the genomic formula AAB1B1, and Johnsongrass is a segmental auto-allo-octoploid, AAAA B1B1B2B2. The model is further substantiated by chromosome pairing in amphiploid plants whose proposed genomic formula is AAAAAA B1B1B1B1 B2B2. PMID- 24232117 TI - Changes in ripening-related processes in tomato conditioned by the alc mutant. AB - The alc mutation affects the ripening and storability of tomato fruit. The alteration of fruit color in alc lines is due to a reduction in total pigment and a reduction in lycopene relative to total carotinoids. Polygalacturonase (PG) activity is reduced to less than 5% of normal, and the isozymes PG2a and PG2b are absent in alc fruit. The level of anti-PG precipitable proteins is also reduced to less than 5% of normal. Total polyA + mRNA is not significantly reduced in ripening alc fruit, but hybridization of polyA + mRNA to different ripening related cDNA clones showed that specific mRNAs are present at reduced levels in the mutant. Specific mRNA levels were reduced to 10%-80% of normal levels, depending on the cDNA clone used as the probe. PG mRNA was present at 5%-10% of the normal level.All effects of alc on fruit ripening are relived in the line Alcobaca-red, which arose spontaneously from the original alc line, Alcobaca. The Alcobaca-red trait segregates as a single dominant trait at or very near the alc locus, and it is probably the result of a reverse mutation at the alc locus.The chromosomal locations of regions homologous to 5 ripening-related cDNA probes were determined. Regions homologous to 4 of these probes map to chromosomes other than chromosome 10, indicating that the effects of alc are transactive. A cDNA clone for PG was homologous to only one chromosomal region. This region is located on chromosome 10, which is also the chromosome on which alc and nor are located. PMID- 24232118 TI - Interspecific hybridization between Nicotiana repanda Willd. and N. tabacum L. through the pollen irradiation technique and the egg cell irradiation technique. AB - Two techniques were useful in overcoming hybrid inviability between N. repanda and N. tabacum. These techniques combine gamma-ray irradiation to pollen or to egg cells (in ovules) with in vitro culture of fertilized ovules. When in vitro culture of fertilized ovules from in situ hybridization of N. repanda x N. tabacum was combined without gamma-ray irradiation to pollen or to egg cells (in ovules), all of the resulting seedlings developed chlorosis and died. Furthermore, in the case of in situ hybridization of N. repanda x N. tabacum with gamma-ray irradiated N. tabacum pollen, no viable seeds were obtained. By using both techniques, combining gamma-ray irradiation to N. tabacum pollen or to egg cells in (N. repanda ovules) with in vitro culture of fertilized ovules, we were successful in obtaining flowering hybrid plants. Thus, it appears that it may be possible to overcome hybrid inviability to a certain extent using both the pollen irradiation technique and the egg cell irradiation technique, i.e., gamma-ray irradiation to pollen or to egg cells (in ovules) before pollination and in vitro culture of fertilized ovules. PMID- 24232119 TI - The use of a triploid hybrid for introgression in Lolium species. AB - Triploid hybrids of Lolium multiflorum (4x) x L. perenne (2x) behaved cytologically as autotriploids but the segregation of isozyme variants did not always agree with the expected trisomic ratios. The overall effect of these deviations from expectation was a greater proportion than expected of diploid progeny from the cross L. multiflorum (2x) x triploid hybrid which did not include any of the L. perenne alleles at the three marker isozyme loci. The possible mechanisms for these aberrant segregation ratios are discussed together with the advantages of the crossing scheme to accelerate the recovery of the genotype of the recurrent parent in a backcrossing programme to transfer characters from one species to another. PMID- 24232120 TI - Cytoplasmic male sterility in Petunia hybrida: factors affecting mitochondrial ATP export in normal and cytoplasmically male sterile plants. AB - In view of accumulating evidence that cytoplasmic male sterility (CMS) in some species results from an inability to generate the high ATP/ADP ratios required for specific stages of differentiation in the reproductive cycle, a number of aspects of ATP metabolism are being examined in CMS and male fertile plants.In experiments designed to test mitochondrial efficiency in ATP export, organelles from CMS plants performed very poorly when compared with normal lines. It is proposed that although most of the molecules involved in mitochondrial ATP production are nuclear encoded, the lesions in mitochondrial (mt)DNA known to accompany the CMS phenotype may be expressed as small modifications within the architecture of the mitochondrial membrane. To detect whether such changes could affect the ADP-ATP translocator in the membrane, two sets of experiments were carried out to determine a 'Km' for the translocator. The two methods employed were based on different precepts, but nevertheless indicated a 'Km' for the mitochondrial translocator in CMS lines which differed dramatically from that of male fertile plants. The view that CMS in Petunia hybrida thus might result from small differences in mtDNA encoded membrane proteins is considered in the light of the cytological changes seen to accompany CMS in these plants, as well as in the context of current theories advanced to explain CMS in other species. PMID- 24232121 TI - Statistical techniques for detection of major genes in animal breeding data. AB - Statistical techniques for detection of major loci and for making inferences about major locus parameters such as genotypic frequencies, effects and gene action from field-collected data are presented. In field data, major genotypic effects are likely to be masked by a large number of environmental differences in addition to additive and nonadditive polygenic effects. A graphical technique and a procedure for discriminating among genetic hypotheses based on a mixed model accounting for all these factors are proposed. The methods are illustrated by using simulated data. PMID- 24232122 TI - Vincristine sulfate liposomal injection for acute lymphoblastic leukemia. AB - Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL. PMID- 24232123 TI - In vitro and in vivo antioxidant activities of a flavonoid isolated from celery (Apium graveolens L. var. dulce). AB - In the present article, a flavonoid was separated and purified from celery leaf through ethanol extraction, column chromatography and crystallization. The product was identified as apiin by LC/ESI-MS, and its antioxidant activities were evaluated in vitro, including by 1,1-diphenl-2-picrylhyrazyl free radical (DPPH), superoxide radical (O2(-)) and hydroxyl radical (OH) scavenging assays. IC50 values were 68.0 MUg ml(-1) in the DPPH assay, 0.39 mg ml(-1) in the O2(-) assay and 48.0 MUg ml(-1) in the OH assay. The antioxidant activities were investigated in vivo with the use of mice models. All data were measured including the contents of maleic dialdehyde (MDA) and lipofuscin (LPF), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (TAOC), in the serum, brain, heart, liver and kidney. Results showed that apiin had a remarkable scavenging activity on MDA and LPF, promoted TAOC and significantly enhanced the activities of SOD, GSH-Px and CAT. PMID- 24232124 TI - Application of a UHPLC MS/MS-based multianalyte approach for screening and validated quantification of drugs in human blood plasma often requested in the context of brain death diagnosis. AB - BACKGROUND: A multianalyte procedure (MAP) for the screening and quantification of drugs of different classes using ultra-high-performance liquid chromatography with tandem-mass spectrometric detection (UHPLC-MS/MS) was established. The aim was to elucidate whether this general approach could be transferred to the determination of drugs relevant for brain death diagnosis (BDD). This part of the MAP should cover alfentanil, etomidate, fentanyl, ketamine, morphine, piritramide, and sufentanil as an addition to the established gas chromatographic mass spectrometric approach for the determination of propofol, barbiturates, and some benzodiazepines. METHODS: This UHPLC-MS/MS approach based on liquid-liquid extraction was validated with respect to selectivity, recovery, matrix effects, process efficiency, ion suppression/enhancement, accuracy and precision, stabilities, and limits of quantification. RESULTS: The approach was selective for the tested analytes. Accurate and precise quantification was achieved for all analytes with the exception of alfentanil and morphine. Validation data for fentanyl, piritramide, and sufentanil were acceptable, but the lowest calibrator concentration had to be set higher than half of the lower therapeutic range as recommended for BDD. CONCLUSIONS: Only etomidate and ketamine fulfill both validation and BDD criteria. Nevertheless, the MAP allowed the simultaneous screening and quantification of >90 other central nervous system-suppressing drugs with the same extract in the same run. For the screening and accurate and precise quantification of low concentrations of alfentanil, fentanyl, morphine, piritramide, and sufentanil, methods with alternative sample preparation and analysis techniques must be developed. PMID- 24232125 TI - Analytical performance of QMS everolimus assay on ortho Vitros 5,1 FS fusion analyzer: measuring everolimus trough levels for solid organ transplant recipients. AB - BACKGROUND: Everolimus has recently been approved by Food and Drug Administration for graft maintenance in liver transplant recipients. This drug has a narrow therapeutic index and benefits from close blood level monitoring. Currently, in the United States, the Thermo Fisher Scientific Quantitative Microsphere System (QMS) Everolimus Immunoassay is the only Food and Drug Administration-cleared immunoassay for monitoring everolimus in renal transplant recipients. However, studies on this assay adapted to the Ortho Vitros 5,1 FS chemistry analyzer have not been published, and data of this assay applied to monitoring drug levels in liver transplant recipients are limited. Here, the authors evaluated and validated the QMS everolimus assay on the Vitros analyzer and its application to supporting the immunosuppressant management of mainly liver transplant recipients. METHODS: The analysis was performed according to the QMS assay package insert. The method was compared with a liquid chromatography-tandem mass spectrometry method from a reference laboratory using a total of 34 samples from 1 double lung and liver, 8 liver, and 3 kidney recipients. The method comparison was assessed by Deming regression. Proficiency test materials issued by Everolimus TDM Proficiency Support Program were tested and compared with the peer group results of using the QMS kits. RESULTS: The assay was linear in the range of 0.75-20.0 ng/mL. Limit of detection was 0.70 ng/mL and lower limit of quantitation was 0.75 ng/mL. Within-day and between-day (20 days) coefficients of variation were between 3.1% and 16.5% at mean levels of 5.3, 12.0, and 17.2 ng/mL, respectively. We obtained a Deming regression of y = 1.271 - 0.666 (r = 0.880) when comparing with the liquid chromatography-tandem mass spectrometry method. CONCLUSIONS: The authors concluded that the analytical performance of the QMS everolimus immunoassay by the Vitros 5,1 FS analyzer was satisfactory for monitoring drug levels of solid organ transplant patients. PMID- 24232126 TI - Dapsone and body mass index in subjects with multibacillary leprosy. AB - BACKGROUND: The physiological changes in obese subjects can modify the pharmacokinetic profiles of drugs influencing the therapeutic efficacy. METHODS: In this study, the authors compare plasma dapsone trough levels of multibacillary leprosy subjects stratified by body mass index (BMI) to evaluate if obesity plays a significant role on drug levels. The relationship between drug levels and BMI was also determined. Dapsone was measured by high-performance liquid chromatography and BMI based on World Health Organization criteria. RESULTS: At steady state, the median plasma dapsone trough level was significantly lower in obesity class 2 group, when compared with other groups, but they were similar between normal weight and preobesity groups. A weak association between drug levels and BMI was observed. CONCLUSIONS: Obesity promotes a significant reduction in plasma dapsone trough levels of subjects with multibacillary leprosy with a weak association between drug levels and BMI. PMID- 24232127 TI - Mycophenolic acid pharmacokinetics in lung transplant recipients with cystic fibrosis. AB - BACKGROUND: Lung transplantation is an established treatment for cystic fibrosis (CF) patients with end-stage lung disease. Current immunosuppression includes the prodrug mycophenolate mofetil (MMF), which has led to improved transplant outcomes. Given the pancreatic insufficiency and malabsorption in CF patients, some transplant centers give higher doses of MMF to these patients based on lower predose levels (C(0)), even though C(0) values correlate poorly with mycophenolic acid (MPA) exposure. The focus of this pilot study was to determine the pharmacokinetics (PK) of MPA in CF when compared with noncystic fibrosis (NCF) lung transplant recipients. METHODS: Five CF and 5 NCF patients had 3 separate PK analyses performed through our clinical research center. In addition to MMF, all patients were on tacrolimus and prednisone and were diabetic on insulin. Twelve hour total serum concentration-time profiles of MPA and MPA glucuronide (MPAG) were obtained after oral administration of MMF. Concentrations of total MPA and MPAG were determined by a validated liquid chromatography-tandem mass spectrometry method. PK parameters of MPA were calculated by the noncompartmental method. Student t test or Mann-Whitney test was used to assess the differences in the PK parameters between the 2 cohorts. RESULTS: CF patients were significantly younger (30.6 versus 59.4 years; P < 0.001) and had significantly lower serum albumin (3.8 versus 4.1 g/dL; P = 0.0018) than NCF patients. CF patients had significantly lower MPA area under the curve (47.7 versus 83.1 mg.h.L(-1); P = 0.016) and MPAG area under the curve (569 versus 911 mg.h.L(-1); P = 0.047) when compared with NCF patients. In addition, C(0) (2.6 versus 4.6 mg/L; P = 0.026) and maximum serum concentration (9.2 versus 20.3 mg/L; P = 0.016) were significantly lower, and apparent oral clearance (0.26 versus 0.13 L.h.kg(-1); P = 0.009) was significantly higher in CF patients. T(max) was delayed in CF patients but not significantly. No difference between CF and NCF patients was observed for intra- and interindividual variability. CONCLUSIONS: Given these results, the lower MPA exposure in CF patients may impact transplant outcome in this lung transplant population. PMID- 24232128 TI - Genotype and allele frequencies of drug-metabolizing enzymes and drug transporter genes affecting immunosuppressants in the Spanish white population. AB - Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy. PMID- 24232129 TI - Serum concentrations of risperidone and aripiprazole in subgroups encoding CYP2D6 intermediate metabolizer phenotype. AB - BACKGROUND: Cytochrome P450 2D6 intermediate metabolizer phenotype (CYP2D6 IM) comprises various genotype subgroups. The aim of this study was to evaluate serum concentrations of the CYP2D6 substrates risperidone and aripiprazole in psychiatric patients with various CYP2D6 genotypes encoding IM phenotype. METHODS: The study was based on therapeutic drug monitoring data from CYP2D6 genotyped patients (mainly of white origin) treated with orally administered risperidone (n = 190) or aripiprazole (n = 266). Patients were divided into 3 genotype subgroups encoding IM phenotype: (1) heterozygous carriers of fully functional and nonfunctional variant alleles (*1/def), (2) homozygous carriers of reduced-function variant alleles (red/red), and (3) heterozygous carriers of reduced-function and nonfunctional variant alleles (def/red). Dose-adjusted serum concentrations of risperidone and aripiprazole were compared between the genotype subgroups using *1/def, the most frequent CYP2D6 genotype among these subgroups, as the reference group. RESULTS: Median serum concentrations were 4.5- and 1.6 fold higher in the def/red genotype than the *1/def genotype for risperidone and aripiprazole, respectively (P < 0.01 for both). Correspondingly, the serum concentrations were 3.4- and 1.8-fold higher in the red/red subgroup compared with the reference group (P < 0.05 for both). CONCLUSIONS: In conclusion, this study revealed substantial variability in serum concentrations of risperidone and aripiprazole between CYP2D6 genotypes associated with IM phenotype. A considerable phenotypical difference was observed between patients carrying 1 and 2 variant alleles. PMID- 24232131 TI - Microstructural and mechanical characterization of contemporary lingual orthodontic brackets. AB - OBJECTIVES: To investigate the composition and the microstructural and mechanical characterization of three different types of lingual brackets. MATERIALS AND METHODS: IncognitoTM (3M Unitek), In-Ovation L (DENTSPLY GAC) and STbTM (Light Lingual System, ORMCO) lingual brackets were studied under the scanning electron microscope employing backscattered electron imaging and their elemental composition was analysed by energy-dispersive X-ray microanalysis. Additionally, Vickers hardness was assessed using a universal hardness-testing machine, and the indentation modulus was measured according to instrumented indentation test. Two way analysis of variance was conducted employing bracket type and location (base and wing) as discriminating variable. Significant differences among groups were allocated by post hoc Student-Newman-Keuls multiple comparison analysis at 95% level of significance. RESULTS: Three different phases were identified for Incognito and In-Ovation L bracket based on mean atomic number contrast. On the contrary, STb did not show mean atomic contrast areas and thus it is recognized as a single phase. Incognito is a one-piece bracket with the same structure in wing and base regions. Incognito consists mainly of noble metals while In-Ovation L and STb show similar formulations of ferrous alloys in wing and base regions. No significant differences were found between ferrous brackets in hardness and modulus values, but there were significant differences between wing and base regions. Incognito illustrated intermediate values with significant differences from base and wing values of ferrous brackets. CONCLUSIONS/IMPLICATIONS: Significant differences exist in microstructure, elemental composition, and mechanical properties among the brackets tested; these might have a series of clinical implications during mechanotherapy. PMID- 24232132 TI - The prepped vaginal canal may be a sterile conduit for ventral hernia mesh insertion: a prospective comparative study. AB - BACKGROUND: Although still experimental, natural orifice translumenal endoscopic surgery (NOTES) aims to use the natural orifices for intraabdominal surgery. Pure transvaginal umbilical hernia repair has been reported. However, mesh protection devices were used to minimize mesh contamination during mesh insertion. The authors believe that before widespread implementation of this technique, more foundational research is indicated to establish the sterility of hernia mesh insertion through this route. This prospective study aimed to compare transvaginal ventral hernia mesh insertion sterility with laparoscopic trocar site insertion sterility to establish baseline data to help promote the safety of NOTES tranvaginal hernia repair. METHODS: This was a prospective descriptive study (Canadian Task Force classification 2A). With institutional review board approval, 10 patients undergoing laparoscopic surgery for benign gynecologic disease were enrolled in the study. Atrium Prolite mesh (polypropylene monofilament) was inserted into the vagina before and after standard surgical preparation with 10 % povidone-iodine. As a control, mesh also was inserted through a prepped laparoscopic port site. The mesh was cultured for bacterial, fungal, and viral contamination. All patients received standard infection prophylaxis that included preoperative intravenous cefazolin and metronidazole. RESULTS: The unprepped vaginal canal was cultured and demonstrated normal multiorganism vaginal flora in all 10 cases. Of the 10 skin incision mesh samples, 3 (30 %) grew bacteria, including Staphylococcus lugdunensis, a potentially pathogenic organism. In contrast, none of the prepped vaginal mesh specimens yielded any growth of microorganisms or potential pathogens. CONCLUSIONS: This study showed that a surgically prepped vaginal canal can be a sterile conduit for insertion of polypropylene mesh for transvaginal ventral hernia repair without the use of additional mesh protection. Surprisingly, the prepped vaginal conduit in our patients was more sterile than a prepped skin incision. PMID- 24232133 TI - Minimally invasive surgery training using multiple port sites to improve performance. AB - BACKGROUND: Structural learning theory suggests that experiencing motor task variation enables the central nervous system to extract general rules regarding tasks with a similar structure - rules that can subsequently be applied to novel situations. Complex minimally invasive surgery (MIS) requires different port sites, but switching ports alters the limb movements required to produce the same endpoint control of the surgical instrument. The purpose of the present study was to determine if structural learning theory can be applied to MIS to inform training methods. METHODS: A tablet laptop running bespoke software was placed within a laparoscopic box trainer and connected to a monitor situated at eye level. Participants (right-handed, non-surgeons, mean age = 23.2 years) used a standard laparoscopic grasper to move between locations on the screen. There were two training groups: the M group (n = 10) who trained using multiple port sites, and the S group (n = 10) who trained using a single port site. A novel port site was used as a test of generalization. Performance metrics were a composite of speed and accuracy (SACF) and normalized jerk (NJ; a measure of movement 'smoothness'). RESULTS: The M group showed a statistically significant performance advantage over the S group at test, as indexed by improved SACF (p < 0.05) and NJ (p < 0.05). CONCLUSIONS: This study has demonstrated the potential benefits of incorporating a structural learning approach within MIS training. This may have practical applications when training junior surgeons and developing surgical simulation devices. PMID- 24232134 TI - 8 years' experience with robotic thymectomy for thymomas. AB - BACKGROUND: The accuracy of a three-dimensional robotic-assisted videothoracoscopic approach may favor a radical resection of thymomas. The aim of this study was to demonstrate the feasibility of the robotic approach by reporting 8 years experience in a single referral center of surgical treatment of thymomas. METHODS: We retrospectively analyzed all consecutive patients who underwent a thymectomy from April 2004 to April 2012. We analyzed the procedure time, morbidity, mortality, conversions, hospitalization, freedom from recurrence, time to progression, and overall survival. RESULTS: From 2004 until 2012, a total of 138 robotic procedures for mediastinal tumors were performed in our center, of which 37 patients with a mean age of 57.3 years underwent a thymectomy for a thymoma. Histological analysis revealed four type A thymomas (10.8 %), seven type AB thymomas (18.9 %), seven type B1 thymomas (18.9 %), fourteen type B2 thymomas (37.8 %), four type B3 thymomas (10.8 %), and one thymus carcinoma (2.7 %). The Masaoka-Koga stages were as follows: stage I in twenty patients (54 %), stage IIA in five patients (13.5 %), stage IIB in eight patients (21.6 %), stage III in three patients (8.1 %), and stage IVa in one patient (2.7 %). The mean overall procedure time was 149 min (range 88-353). No surgical mortality was reported, and there were no peri-operative complications. No conversions were needed for surgical complications. In three cases, a conversion to sternotomy was preferred by the surgeon because tumor invasion in greater vessels was suspected. Two patients (5.4 %) suffered from a myasthenic crisis postoperatively and required prolonged mechanical ventilation. One patient (2.7 %) underwent a procedure for a thoracic herniation 6 months following thymectomy. The median hospitalization was 3 days. The follow-up analysis showed an overall survival of 100 % and tumor recurrence in one patient (2.7 %). CONCLUSIONS: Robotic thymectomies are safe in patients with early-stage thymomas. Robotic surgery may also be feasible for some selected advanced thymomas. PMID- 24232135 TI - Surgical outcomes in the newly introduced phase of intracorporeal anastomosis following laparoscopic distal gastrectomy is safe and feasible compared with established procedures of extracorporeal anastomosis. AB - BACKGROUND: Totally laparoscopic distal gastrectomy (TLDG) with intracorporeal anastomosis has been introduced to achieve safer anastomosis with good vision, and a small wound. However, little is known about the surgical outcomes of newly introduced TLDG compared with established procedures of laparoscopy-assisted gastrectomy (LADG) with extracorporeal anastomosis. METHODS: This retrospective study included 114 patients who underwent laparoscopic distal gastrectomy (LDG) between January 2010 and September 2012. The patients were classified into two groups according to the approach of reconstruction (LADG group: n = 74; TLDG group: n = 40). The parameters analyzed included patients, operation details, and operative outcomes. RESULTS: No complication was observed in the TLDG group. Surgical outcomes of the TLDG group, such as mean operation time, estimated blood loss, and rate of conversion to laparotomy were not inferior to the LADG group. Furthermore, postoperative hospital stay of the TLDG group was significantly shorter than the LADG group (p < 0.05). CONCLUSION: Surgical outcomes in the newly introduced phase of TLDG were safe as well as feasible compared with established LADG. TLDG has several advantages over LADG, such as shorter post hospital stay, no incidence of operative complication, adequate working space, and small wound size. Although prospective, randomized control studies are warranted, we submit that TLDG can be used as a standard procedure for LDG. PMID- 24232136 TI - Freeze-fracture observations on membranes of dry and hydrated pollen from Collomia, Phoenix and Zea. AB - Pollen from Collomia grandiflora Dougl. ex Lindl., Phoenix dactylifera L. and Zea mays L. was examined by freeze-fracture electron microscopy. Particular attention was paid to the organization of the cell membranes in the naturally dehydrated, as compared to the fully hydrated, state. All membranes examined had a normal bilayer organization similar to that seen in the hydrated cells of these and other plants. This organization of dry pollen membranes is discussed as it relates to physiological studies (e.g., leakage of ions during hydration), and to biophysical properties of biological and model membranes under various conditions of hydration and dehydration. PMID- 24232137 TI - Intracellular localisation of phytochrome in oat coleoptiles by electron microscopy. AB - We have analysed the intracellular localisation of phytochrome in oat coleoptile cells by electron microscopy and confirm and extend light-microscopical findings of previous authors. We used indirect immuno-labeling with polyclonal antibodies against 60-KDa phytochrome from etiolated oat seedlings, and a gold-coupled second antibody, on ultrathin sections of LR-white-embedded material. In dark grown seedlings, phytochrome-labeling is distributed diffusely throughout the cytoplasm. Organelles and membranes are not labeled. After photoconversion of the red-absorbing form of phytochrome to the far-red absorbing form (Pfr) (5-min red light; 660 nm), the label is sequestered uniquely in electron-dense areas within the cytoplasm. These areas are irregularly shaped, are often located in the vicinity of the vacuole, are not surrounded by a membrane, exclude cellular organelles and ribosomes and are not found in dark-grown material; an immediate 5 min farred light pulse after the red light does not cause these structures to disappear. After a dark period of 3-4 h following red-light irradiation, these electron-dense structures disappear together with any specific labeling. We suggest a Pfr-induced aggregation of an unknown, phytochrome-binding protein or proteins. PMID- 24232138 TI - A single positive phototropic response induced with pulsed light in hypocotyls of Arabidopsis thaliana seedlings. AB - The fluence-response curves were measured for phototropic curvature in response to unilateral 450-nm light in hypocotyls of Arabidopsis thaliana (L.) Heynh. These show the classical "first positive" (peak curvature of 9-10 degrees ), "indifferent" and "second positive" phototropic response. Reciprocity is valid only for the "first positive" response; the fluence requirements for its induction are similar to those for induction of the "first positive" phototropic response of coleoptiles. Large angles of curvature also may be induced by multiple pulses if the individual pulses are separated by an optimum dark period of about 15 min. The curvature induced by a given fluence, whether applied in continuous irradiation or a sequence of pulses, is a linear function of the duration of continuous irradiation or the duration between first and last pulse, respectively. For a given fluence applied in a sequence of pulses, reciprocity remains valid provided the duration between first and last exposure is kept constant. When the duration between first and last pulse is sufficiently long, the fluence required for high phototropic curvature falls in the "first positive" fluence range. These results are interpreted to indicate the existence of a kinetic limitation in the transduction sequence, and a relatively short lifetime of an initial physiologically active photoproduct. The apparent existence of more than one positive response may have resulted from these characteristics of the transduction sequence. PMID- 24232139 TI - Carbon and nitrogen metabolism in barley (Hordeum vulgare L.) mutants lacking ferredoxin-dependent glutamate synthase. AB - Five mutant lines of barley (Hordeum vulgare L.), which are only able to grow at elevated levels of CO2, contain less than 5% of the wild-type activity of ferredoxin-dependent glutamate synthase (EC 1.4.7.1). Two of these lines (RPr 82/1 and RPr 82/9) have been studied in detail. Leaves and roots of both lines contain normal activities of NADH-dependent glutamate synthase (EC 1.4.1.14) and the other enzymes of ammonia assimilation. Under conditions that minimise photorespiration, both mutants fix CO2 at normal rates; on transfer to air, the rates drop rapidly to 15% of the wild-type. Incorporation of (14)CO2 into sugar phosphates and glycollate is increased under such conditions, whilst incorporation of radioactivity into serine, glycine, glycerate and sucrose is decreased; continuous exposure to air leads to an accumulation of (14)C in malate. The concentrations of malate, glutamine, asparagine and ammonia are all high in air, whilst aspartate, alanine, glutamate, glycine and serine are low, by comparison with the wild-type parent line (cv. Maris Mink), under the same conditions. The metabolism of [(14)C]glutamate and [(14)C]glutamine by leaves of the mutants indicates a very much reduced ability to convert glutamine to glutamate. Genetic analysis has shown that the mutation in RPr 82/9 segregates as a single recessive nuclear gene. PMID- 24232140 TI - Carbon and nitrogen metabolism in a barley (Hordeum vulgare L.) mutant with impaired chloroplast dicarboxylate transport. AB - A mutant line, RPr79/2, of barley (Hordeum vulgare L. cv. Maris Mink) has been isolated that has an apparent defect in photorespiratory nitrogen metabolism. The metabolism of (14)C-labelled glutamine, glutamate and 2-oxoglutarate indicates that the mutant has a greatly reduced ability to synthesise glutamate, especially in air, although in-vitro enzyme analysis indicates the presence of wild-type activities of glutamine synthetase (EC 6.3.1.2) glutamate synthase (EC 1.4.7.1 and EC 1.4.1.14) and glutamate dehydrogenase (EC 1.4.1.2). Several characteristics of RPr79/2 are very similar to those described for glutamate synthase-deficient barley and Arabidopsis thaliana mutants, including the pattern of labelling following fixation of (14)CO2, and the rapid rise in glutamine content and fall in glutamate in leaves on transfer to air. The CO2-fixation rate in RPr79/2 declines much more slowly on transfer from 1% O2 to air than do the rates in glutamate-synthase-deficient plants, and RPr79/2 plants do not die in air unless the temperature and irradiance are high. Analysis of (glutamine+NH3+2 oxoglutarate)-dependent O2 evolution by isolated chloroplasts shows that chloroplasts from RPr79/2 require a fivefold greater concentration of 2 oxoglutarate than does the wild-type for maximum activity. The levels of 2 oxoglutarate in illuminated leaves of RPr79/2 in air are sevenfold higher than in Maris Mink. It is suggested that RPr79/2 is defective in chloroplast dicarboxylate transport. PMID- 24232141 TI - Changes in topography and function of thylakoid membranes following membrane protein phosphorylation. AB - Changes in topography and function of pea (Pisum sativum L.) thylakoid membrane fractions following membrane protein phosphorylation have been studied. After protein phosphorylation the stromal membrane fraction had a higher chlorophyll a/b ratio, an increased content of light-harvesting chlorophyll protein and a higher ratio of chlorophyll to cytochrome f. This indicates that a pool of light harvesting chlorophyll protein migrates from the photosystem II-enriched grana regions to the photosystem I-enriched stroma lamellae, in agreement with Kyle et al. (1984, Biochim. Biophys. Acta 765, 89-96) and Larsson et al. (1983, Eur. J. Biochem. 136, 25-29). Phosphorylation caused a stimulation in the rate of light limited photosystem-I electron transfer in the unappressed membrane fraction, indicating that the translocated LHC-II becomes functionally associated with photosystem I. PMID- 24232142 TI - Effects of light and temperature on sporangiophore initiation in Pilobolus crystallinus (Wiggers) Tode. AB - Sporangiophore initiation in Pilobolus crystallinus grown in white light was induced by either a dark or a low-temperature treatment. The period of darkness necessary to induce sporangiophore initiation was shortened by lowering the temperature. Arrhenius plots for the sporangiophore-suppressing reaction in both light and darkness consisted of two straight lines with a Q10 of about 2 at lower temperatures and 8-11 at higher temperatures. The temperature at which the Q10 changed was the lower, the higher the fluence rate: 14 degrees C at 8 W/m(2), 19.5 degrees C at 0.24 W/m(2) and 24.5 degrees C in darkness. Possible interpretations of these results are briefly presented. PMID- 24232143 TI - Benzyladenine modulation of the expression of two genes for nuclear-encoded chloroplast proteins in Lemna gibba: Apparent post-transcriptional regulation. AB - Cytokinins and phytochrome have both been reported to promote chloroplast development, and possible interactions between the two have been suggested. We have examined the effects of red light (R) and a cytokinin, benzyladenine (N(6) benzylaminopurine; BA), on the levels of four mRNAs coding for chloroplast proteins in Lemna gibba L. The amounts of hybridizable RNA coding for both the major chlorophyll a/b-binding protein and for the small subunit of ribulose-1,5 bisphosphate (RuBP) carboxylase decrease to a low level when white-light-grown L. gibba plants are placed in the dark. We have previously shown that a subsequent R treatment causes a several-fold increase in the levels of these two messages, and this increase is phytochrome-mediated. We have now found that addition of submicromolar concentrations of BA to plants kept in total darkness also results in an increase in levels of these two mRNAs. Furthermore, BA treatment magnifies the extent of the response to R treatment. However, the levels of mRNAs encoding the large subunit of RuBP carboxylase and the 32-kDa herbicide-binding protein, which are both chloroplastsynthesized messages, are not significantly altered by either R or BA treatment during the same time period. The relative amount of beta actin mRNA, a nuclear-encoded message for a cytoplasmic protein, is also not altered either by R or BA treatment. Thus, BA treatment does not simply alter the proportion of mRNA to total RNA. This conclusion is also supported by the observation that levels of mRNA hybridizing to a sequence abundant in dark treated plants are not altered by BA treatment. The amplification by BA of the R induced increase in the level of chlorophyll a/b-binding protein mRNA, consistently seen in total RNA, is not observed in RNA isolated from nuclei from plants receiving the same treatments. We therefore suggest that cytokinin is regulating expression of this message at a post-transcriptional level, possibly by affecting the stability of the RNA. PMID- 24232144 TI - Correlation between infection by Rhizobium leguminosarum and lectin on the surface of Pisum sativum L. roots. AB - The lectin on the surface of 4- and 5-dold pea roots was located by the use of indirect immunofluorescence. Specific antibodies raised in rabbits against pea seed isolectin 2, which crossreact with root lectins, were used as primary immunoglobulins and were visualized with fluorescein- or tetramethylrhodamine isothiocyanate-labeled goat antirabbit immunoglobulin G. Lectin was observed on the tips of newly formed, growing root hairs and on epidermal cells located just below the young hairs. On both types of cells, lectin was concentrated in dense small patches rather than uniformly distributed. Lectin-positive young hairs were grouped opposite the (proto)xylematic poles. Older but still-elongating root hairs presented only traces of lectin or none at all. A similar pattern of distribution was found in different pea cultivars, as well as in a supernodulating and a non-nodulating pea mutant. Growth in a nitrate concentration which inhibits nodulation did not affect lectin distribution on the surface of pea roots of this age. We tested whether or not the root zones where lectin was observed were susceptible to infection by Rhizobium leguminosarum. When low inoculum doses (consisting of less than 10(6) bacteria.ml(-1)) were placed next to lectin-positive epidermal cells and on newly formed root hairs, nodules on the primary roots were formed in 73% and 90% of the plants, respectively. Only a few plants showed primary root nodulation when the inoculum was placed on the root zone where lectin was scarce or absent. These results show that lectin is present at those sites on the pea root that are susceptible to infection by the bacterial symbiont. PMID- 24232145 TI - Movement and compartmentation of abscisic acid in guard cells of Valerianella locusta: Effects of osmotic stress, external H(+)-concentration and fusicoccin. AB - Epidermal peels of Valerianella locusta were acid-treated for 1 h at pH 3.9 to kill all cells other than guard cells. These guard-cell preparations were used to explore the steady-state one-way fluxes and the cytoplasmic and vacuolar contents of abscisic acid (ABA). The method of compartmental analysis has been applied. The intracellular ABA concentrations were surprisingly high. At an external pH of 5.8 the cytoplasm contained 1.28 mmol.dm(-3) of ABA, twice of the amount which accumulated in the vacuoles (0.57 mmol.dm(-3)). The fluxes of ABA at the plasmalemma (phioc=phioc=0.43 fmol . cell (-1) . h (-1)) were higher than those at the tonoplast (phicv=phivc=0.12 fmol . cell (-1) . h (-1)). Moderate stress (0.1 and 0.3 mol.dm(-3) sorbitol in the medium) caused a change in the kinetics of ABA movement. The rate constants of the fluxes from the cytoplasm into the vacuole (phicv) and into the apoplast (phico) were increased while the rate constant of the flux from the vacuoles into the cytoplasm (phivc) was decreased. As a consequence the amount of ABA sequestered in the vacuole remained unchanged; the cytoplasmic ABA content, however, was reduced to only 20% of that found in the control treatments (no sorbitol in the medium). Under moderate stress, one Valerianella guard cell released rapidly about 0.36 fmol.cell(-1) to its direct cell-wall space. This surprising result is discussed in regard to rapid stomatal closure under reduced water supply. PMID- 24232146 TI - Appearance of nitrite reductase in cotyledons of the mustard (Sinapis alba L.) seedling as affected by nitrate, phytochrome and photooxidative damage of plastids. AB - Nitrite reductase (NIR; EC 1.7.7.1) is a central enzyme in nitrate assimilation and is localized in plastids. The present study concerns the regulation of the appearance of NIR in cotyledons of the mustard (Sinapis alba L.) seedling. It was shown that light exerts its positive control over the nitrate-mediated induction of NIR via the farred-absorbing form of phytochrome. Without nitrate the light effect cannot express itself; even though the light signal is accumulated in the cotyledons it remains totally cryptic in the absence of nitrate. Moreover, it was recognised that 'intact plastids' are important in the control of the appearance of NIR. If the plastids are damaged by photooxidation the action of nitrate and phytochrome on NIR appearance is abolished. The appearance of nitrate reductase (NR; EC 1.6.6.1) responds similarly to photooxidative damage even though this enzyme is cytosolic. While the data strongly indicate that some 'plastidic signal' is a prerequisite for the nitrate-induced and phytochrome-modulated appearance of NIR and NR, the possibility could not be ruled out that photooxidative damage affects the accumulation of NIR in the organelle. PMID- 24232147 TI - Plasmodesmatal frequency and radial translocation rates in ray cells of poplar (Populus x canadensis Moench 'robusta'). AB - The minimum radial translocation rate of sugars has been determined from the starchaccumulation rate for the wood rays of Populus x canadensis Moench 'robusta', and related to ultrastructural peculiarities of the cell walls to be passed. The minimum radial flux or flow of sugars through the tangential walls, the pit fields, and per plasmodesma was 80.7 pmol . cm(-2) . s(-1), 400 to 800 pmol . cm(-2) . s(-1), and 1.0 to 1.7 . 10(-7) pmol . plasmodesma(-1) . s(-1), respectively. These values exclude a transmembrane flux mechanism and indicate that the radial translocation in this tissue must proceed via plasmodesmata. In the isolation cells of the ray center we found 39 plasmodesmata per MUm(2) of pit field, 8.0 per MUm(2) of tangential wall, and 1.98% of the wall occupied by plasmodesmata. Cells of the ray margins show plasmodesmata on only 1.16% of their tangential wall area and thus appear to be slightly inferior for radial translocation. As judged from both the observed plasmodesmatal frequencies and the translocation rates, the ray parenchyma cells are comparable to cells specialized in short-distance translocation. PMID- 24232148 TI - Characterization of the glutamate/aspartate-transport system in a symbiotic Nostoc sp. AB - The permeability properties of the cell membrane of a symbiotic Nostoc sp. for glutamate and aspartate were investigated. These compounds were translocated across the plasmalemma by a transport system which showed a very high affinity for glutamate and a lower one for aspartate. Since a concomitant release of glutamate was observed during the uptake of these two amino acids it is concluded that the transport proceeds via a counterexchange mechanism. In addition to this counterexchange a net release of glutamate occurred in the dark. Some aspects concerning the possible function of this transport system in the symbiotic association Geosiphon pyriforme are discussed. PMID- 24232149 TI - Patatin, a major soluble protein of the potato (Solanum tuberosum L.) tuber is synthesized as a larger precursor. AB - Antibodies were raised against the highly purified glycoprotein patatin. They were used to characterize the product synthesized in a wheatgerm cell-free translation system, programmed with polyadenylated RNA from potato tubers. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed that the immunoprecipitated protein had a molecular mass of 43 kDa compared to 40 for the authentic patatin. It is assumed that patatin is synthesized in vivo as a larger precursor which is processed to the mature protein by cleavage of a signal peptide. Our results are in agreement with sequence-analysis data of patatin complementary DNA which indicate a signal peptide of about 23 amino acids (Mignery et al., 1984; Nucleic Acids Res. 12, 7987-8000). PMID- 24232150 TI - Enzyme activities in mitochondria isolated from ripening tomato fruit. AB - Mitochondria were isolated from tomato (Lycopersicon esculentum L.) fruit at the mature green, orange-green and red stages and from fruit artificially suspended in their ripening stage. The specific activities of citrate synthase (EC 4.1.3.7), malate dehydrogenase (EC 1.1.1.37), NAD-linked isocitrate dehydrogenase (EC 1.1.1.41) and NAD-linked malic enzyme (EC 1.1.1.38) were determined. The specific activities of all these enzymes fell during ipening, although the mitochondria were fully functional as demonstrated by the uptake of oxygen. The fall in activity of mitochondrial malate dehydrogenase was accompanied by a similar fall in the activity of the cytosolic isoenzyme. Percoll-purified mitochondria isolated from mature green fruit remained intact for more than one week and at least one enzyme, citrate synthase, did not exhibit the fall in specific activity found in normal ripening fruit. PMID- 24232151 TI - Microcallus formation from maize protoplasts prepared from embryogenic callus. AB - Conditions have been developed that induce maize (Zea mays L.) protoplasts to re synthesize cell walls and to initiate cell divisions. Two types of embryogenic maize callus were used as a source of protoplasts: a heterogeneous callus (Type I) derived from immature embryos after three weeks in culture, and a friable, rapidly growing callus (Type II) selected from portions of the Type I callus. Many variables in the growth conditions of the donor tissue (type of medium, transfer schedule, age of callus), protoplast isolation solutions (pH, osmolarity, type and concentration of cell wall hydrolyzing enzymes, addition of polyamines) and conditions (amount of time in enzyme, amount of tissue per volume of enzyme incubation medium, agitation, preplasmolysis of source tissue, type of callus), and purification procedures (filtration and-or flotation), were found to affect both yield and viability of protoplasts (based upon fluorescein-diacetate staining). Our isolation procedure yielded high numbers of viable, uninucleated maize callus protoplasts which were densely cytoplasmic and varied in size from 20 to 50 MUm in diameter. Protoplasts plated in solid medium formed walls and divided several times. Of several gelling agents tested for protoplast propagation, only agarose resulted in protoplasts capable of sustained divisions leading to the formation of microcalli. Plating efficiency was established over a wide range of protoplast densities (10(3)-10(7) protoplasts/ml). Highest plating efficiency (25%) was obtained at 1.10(6) protoplasts/ml). The resulting microcalli grew to be dense clusters of about 0.1-0.5 mm in diameter and then stopped growing. Nurse cultures of maize and carrot (Daucus carota L.), were used to establish that individual protoplasts (not contaminating cells or cell clusters) formed walls and divided. Nurse cultures also increased the efficiency of microcallus formation from protoplasts. PMID- 24232152 TI - Regulation in tobacco callus of enzyme activities of the nicotine pathway : I. The route ornithine to methylpyrroline. AB - Nicotine synthesis was stimulated by reduction of the medium auxin concentration (induction medium) in callus tissue originating from Nicotiana tabacum cv. Samsun. The enzyme activities of the route ornithine to methylpyrroline, which are those of ornithine decarboxylase, putrescine methyltransferase and methylputrescine oxidase, were determined during callus growth in the induction medium and as a control under non-nicotine-stimulating conditions (growth medium). The enzymes were assayed by high-performance liquid chromatography. Whereas the activities of ornithine decarboxylase were very similar under nicotine-stimulating and non-stimulating conditions, those of putrescine methyltransferase and methyl-putrescine oxidase increased strongly in the induction medium. In addition, the pools of putrescine and methylputrescine were determined throughout the callus growth cycle. Both sets of data strongly confirm the supposition that putrescine methyl-transferase is the enzyme under stringent control for nicotine biosynthesis, whereas the subsequent methylputrescine oxidase is co-regulated, although less stringently. PMID- 24232153 TI - Regulation in tobacco callus of enzyme activities of the nicotine pathway : II. The pyridine-nucleotide cycle. AB - In tobacco callus, the induction of nicotine synthesis, which stimulates enzyme activities of the ornithine-methylpyrroline route (see the preceding paper), also leads to marked changes in the enzyme activities of the pyridine-nucleotide cycle. This cycle provides the metabolite (probably nicotinic acid) for condensation with methylpyrroline to produce nicotine. The activities of eight enzymes of the pyridine-nucleotide cycle and of quinolinic-acid phosphoribosyltransferase, the anaplerotic enzyme, were determined by high performance liquid chromatography assays. The distinct changes of their activities upon induction of nicotine synthesis lead to the following conclusions: i) nicotinic acid is the relevant metabolite which is provided by the pyridine-nucleotide cycle and consumed for nicotine synthesis. ii) The enhancement of the nicotinic-acid pool arises in two ways, by synthesis of NAD and degradation via nicotinamide mononucleotide and by a direct route from nicotinic-acid mononucleotide (NaMN) which is degraded by a glycohydrolase with a rather high K m value. Such a K m value prevents the complete depletion of the NaMN pool. PMID- 24232154 TI - The quantitative relationship between gibberellin A1 and internode growth in Pisum sativum L. AB - The metabolism and growth-promoting activity of gibberellin A20 (GA20) were compared in the internode-length genotypes of pea, na le and na Le. Gibberellin A29 and GA29-catabolite were the major metabolites of GA20 in the genotype na le. However, low levels of GA1, GA8 and GA8-catabolite were also identified as metabolites in this genotype, confirming that the le allele is a 'leaky' mutation. Gibberellin A20 was approximately 20 to 30 times as active in promoting internode growth of genotype na Le as of genotype na le. However, the levels of the 3beta-hydroxylated metabolite of GA20, GA8 (2beta-hydroxy GA1), were similar for a given growth response in both genotypes. In each case a close linear relationship was observed between internode growth and the logarithm of GA8 levels. A similar relationship was found on comparing GA20 metabolism in the three genotypes le (d), le and Le. The former mutation results in a more severe dwarf phenotype than the le allele (which has previously been shown to reduce the 3beta-hydroxylation of GA20 to GA1). These results indicate that GA20 has negligible intrinsic activity and support the contention that GA1 is the only GA active per se in promoting stem growth in pea. PMID- 24232156 TI - Erratum. PMID- 24232155 TI - Sodium, potassium, chloride and proline concentrations of chloroplasts isolated from a halophyte, Mesembryanthemum crystallinum L. AB - Concentrations of four major solutes (Na(+), K(+), Cl(-), proline) were determined in isolated, intact chloroplasts from the halophyte Mesembryanthemum crystallinum L. following long-term exposure of plants to three levels of NaCl salinity in the rooting medium. Chloroplasts were obtained by gentle rupture of leaf protoplasts. There was either no or only small leakage of inorganic ions from the chloroplasts to the medium during three rapidly performed washing steps involving precipitation and re-suspension of chloroplast pellets. Increasing NaCl salinity of the rooting medium resulted in a rise of Na(+) und Cl(-) in the total leaf sap, up to approximately 500 and 400 mM, respectively, for plants grown at 400 mM NaCl. However, chloroplast levels of Na(+) und Cl(-) did not exceed 160 230 and 40-60 mM, respectively, based upon a chloroplast osmotic volume of 20-30 MUl per mg chlorophyll. At 20 mM NaCl in the rooting medium, the Na(+)/K(+) ratio of the chloroplasts was about 1; at 400 mM NaCl the ratio was about 5. Growth at 400 mM NaCl led to markedly increased concentrations of proline in the leaf sap (8 mM) compared with the leaf sap of plants grown in culture solution without added NaCl (proline 0.25 mM). Although proline was fivefold more concentrated in the chloroplasts than in the total leaf sap of plants treated with 400 mM NaCl, the overall contribution of proline to the osmotic adjustment of chloroplasts was small. The capacity to limit chloroplast Cl(-) concentrations under conditions of high external salinity was in contrast to an apparent affinity of chloroplasts for Cl(-) under conditions of low Cl(-) availability. PMID- 24232157 TI - Clarification on the legal status of human remains in university collections of human anatomy in France. PMID- 24232158 TI - Scanning electron microscopy and epifluorescence investigation of bacterial colonization of marine sand sediments. AB - Scanning electron microscopy (SEM) was employed for the investigation of microorganisms living in marine sand sediments. Epifluorescence, as well as sediment analyses, gave further data on the parameters of the sediment samples.SEM revealed a correlation between the site and density of bacterial colonization and the microtopography of the individual sand grains.Sand grains with a medium roundness showed the greatest density of bacterial colonization. Protected surface sites were favored in the colonization process. The mode of bacterial attachment varied; mostly the barren sand grain surface was colonized. However, bacteria were also observed close to or within detritus or attached to diatoms. Many of the attaching bacteria observed were found to produce polymer strands.In some cases special structures were discovered which could serve bacterial attachment. Entire colonies attached by means of polymer nets, and disc shaped bacteria were observed. PMID- 24232159 TI - Behavior, activities, and effects of bacteria on synthetic quartz monocrystal surfaces. AB - Two strains ofBacillus sp. and a strain ofBrevibacterium sp., originally isolated from a natural quartzite surface, were characterized and employed as test strains with several methods: acridine orange fluorochromation and epifluorescence microscopy were used for detection of individual cells; scanning and transmission microscopy for studying attachment behavior; replica techniques in combination with electron microscopy for following surface interaction effects; and chemical analysis of SiO2 for detecting possible silica leaching activities. The experimental results clearly showed that the three test strains were able to attach to and grow on the precleaned quartz surfaces. Attachment modes were either by direct sorption mechanisms (Brevibacterium sp. S) or the production of adhesive polymers (Bacillus sp. U andBacillus sp. W). In short-term contact incubation experiments with rich media, neither quartz crystal surface structures nor bacterial cell surfaces appeared to be changed. Likewise, significant biochemical dissolution and mechanical dislocation of SiO2 (which would have indicated rapid bacterial weathering activities) could not be detected. The importance of quartz purity and crystalline structure for the initiation of weathering processes is discussed. PMID- 24232160 TI - Growth responses of ciliate protozoa to the abundance of their bacterial prey. AB - The growth rate or numerical response of five species of bactivorous ciliates to the abundance ofEnterobacter aerogenes was examined in monoxenic culture. The ciliatesColpidium campylum, C. colpoda, Glaucoma scintillons, G. frontata, andCyclidium glaucoma were isolated from a small pond. Four were grown in shaken cultures, while three were grown in cultures in which the bacteria were allowed to settle on the bottom of the culture vessel. Of the seven response curves generated, four had distinct thresholds, so that the Michaelis-Menten model usually fitted to ciliate numerical response curves was not appropriate. In shaken cultures, half-saturation prey densities ranged from 5.5 * 10(6) to 42.9 * 10(6) bacteria/ml. In unshaken cultures, half-saturation densities ranged from 0.057 * 10(6) to 14.6 * 10(6) bacteria/cm(2). Two species grown on both suspended and settled bacteria attained higher growth rates and had lower half-saturation prey densities feeding on settled bacteria. PMID- 24232161 TI - Role of heterotrophic bacteria in promoting N2 fixation byAnabaena in aquatic habitats. AB - Anabaena species are commonly colonized by bacteria, especially during N2-fixing blooms. Generally these associations do not represent bacterial attack on algal hosts. Instead, the algal N2-fixing capabilities are increased in the presence of the bacteria. Possible mechanisms promoting the mutual growth of algae and attached bacteria were investigated by observing specific sites of bacterial attachment, by noting reduced microzones created by the bacteria, and by locating sites of bacterial uptake of organics representative of algal excretion products.Attached bacteria show preference for typical algal excretion products and their growth is enhanced by such products. In return, enhancement of algal nitrogenase activity occurs when bacteria create O2-consuming microzones around the nitrogenase-bearing heterocysts. PMID- 24232162 TI - Nitrifying populations and the destruction of nitrogen dioxide in soil. AB - The nitrite formed from nitrogen dioxide (NO2) was oxidized more readily in soil that had been treated previously with the gas than in soil not so pre-exposed. The reaction was inhibited by 1.0 but not by 0.01 mM chlorate. The population of nitrite-oxidizing autotrophs estimated by the most-probable-number procedure was too small and often grew too late to account for oxidation of the nitrite generated from NO2. The reaction also proceeded in soil heated to 42 degrees to 45 degrees C or treated with 0.16 mM chlorate, although the countable autotrophs did not increase during the transformation or grew only late in the active period of nitrite oxidation. The data suggest that unknown populations are responsible for metabolism of the nitrite produced from NO2 entering soil. PMID- 24232163 TI - Product inhibition in sludge digestion. AB - Hydrogen and acetate inhibit the microbial degradation of propionate and ethanol in digesting sludge. Propionate oxidation is more sensitive than ethanol oxidation to product activities. This difference can be explained on thermodynamic grounds. It is concluded that the limiting factors for complete anaerobic mineralization of biodegradable organic matter in digesting sludge are to be sought in the boundary conditions for the exergonic oxidation of propionate. The different ecological significances of hydrogen and acetate as inhibitory agents of fatty acid degradation in sludge digestion are discussed. Hydrogen partial pressure and alkalinity are recommended as parameters in monitoring sludge digestion. PMID- 24232164 TI - Methanogenic fermentation of benzoate in an enrichment culture. AB - Enrichment cultures inoculated with black mud fermented benzoate according to the stoichiometric equation: 4 C6H5CO2H+18 H2O -> 15 CH4+13 CO2.Trans-2 hydroxycyclohexanecarboxylate, 2-oxo-cyclohexanecarboxylate, pimelate, caproate, butyrate, acetate, and molecular hydrogen were shown to be regular components of the culture fluid occurring in low concentrations. Inhibition of methanogenesis by chloroform, 4-chlorobutyrate, or 2-bromooctanoate resulted in a cessation of the benzoate breakdown after all intermediates had accumulated. It is proposed that benzoate is fermented via a direct reductive pathway to butyrate, acetate, H2, and CO2, whereafter butyrate is converted to acetate and H2, and the latter substrates are fermented to CH4 and CO2 by methane producers. PMID- 24232165 TI - Most-probable-number technique for the enumeration of aromatic degraders in natural environments. AB - A most-probable-number (MPN) method is described for the enumeration of heterotrophic populations capable of utilizing chlorinated and nonchlorinated benzoates and phenols as sole carbon sources. A correlation coefficient of 0.91 was obtained between the numbers determined by the MPN technique and the standard plate count. The MPN method gave realistic cell counts when population densities were low, and the presence of oligocarbophiles did not give spurious results. PMID- 24232166 TI - Bacterioneuston examined with critical point drying and transmission electron microscopy. AB - Morphological details of bacteria collected at the air/seawater interface are greatly enhanced when transmission electron microscopy is coupled with critical point dried preparations. Few artifacts and minimal distortion permit a more accurate appraisal of an organism's cell characteristics and its relationship to its microenvironment. Cell surface and extracellular polymer materials are clearly distinguished in a manner not feasible with other preparations. PMID- 24232167 TI - May autonomic indices from cardiovascular variability help identify hypertension? AB - INTRODUCTION: Altered profile of RR variability and reduced baroreflex gain, as autonomic proxies, are observed in hypertensive individuals. AIM: To assess whether using logistic models and cross-validation techniques autonomic proxies can be used to identify clinical hypertensive and normotensive groups. METHODS: An observational study on 405 individuals (155 mild hypertensive and 250 controls). We used four steps for statistical analysis: preliminary descriptive statistics; logistic regression modelling; detection of best parsimonious set of variables; and concordance analysis between clinical and autonomic hypertension profile. RESULTS: Accuracy index (rate of correct identifications of normotensive and hypertensive states), computed on each of the four gradually more complex logistic models (from A to D), reached its highest value (82.7%), in the most complete model D, including autonomic nervous system indices (RR variability and baroreflex gain), age and sex. Measures of predictive performance increased from the simplest model to the most complex one [model D, positive predictive value (PPV) = 0.767, negative predictive value (NPV) = 0.866], with higher specificity than sensitivity. A parsimonious set of autonomic proxies (Mean RR, DeltaRRLFnu - i.e. change from rest to standing up - baroreflex gain combined with age and sex) led to an accuracy index of 80.5%, thus proving to have discriminant and predictive powers in detecting hypertension very similar to the whole set of the explicative variables comprised in the complete model D. CONCLUSION: The clinical value of the observation that the information collectively carried by a small subset of indirect autonomic proxies may identify either hypertensive or normotensive groups needs to be further investigated. PMID- 24232169 TI - Do 5-Year-Old Children Perform Dual-Task Coordination Better Than AD Patients? AB - OBJECTIVE: A cross-sectional study was carried out to examine the pattern of changes in the capacity to coordinate attention between two simultaneously performed tasks in a group of 570 volunteers, from 5 to 17 years old. METHOD: The results revealed that the ability to coordinate attention increases with age, reaching adult values by age 15 years. Also, these results were compared with the performance in the same dual task of healthy elderly and Alzheimer disease (AD) patients found in a previous study. RESULTS: The analysis indicated that AD patients showed a lower dual-tasking capacity than 5-year-old children, whereas the elderly presented a significantly higher ability than 5-year-old children and no significant differences with respect to young adults. CONCLUSION: These findings may suggest the presence of a working memory system's mechanism that enables the division of attention, which is strengthened by the maturation of prefrontal cortex, and impaired in AD. PMID- 24232168 TI - Oxidative Stress and ADHD: A Meta-Analysis. AB - OBJECTIVE: To clarify the role of oxidative stress and antioxidant activity in ADHD. METHOD: We examined the association of ADHD and oxidative stress by applying random effects meta-analysis to studies of oxidative stress and antioxidant status in medication naive patients with ADHD and controls. RESULTS: Six studies of a total of 231 ADHD patients and 207 controls met our selection criteria. The association between ADHD and antioxidant status was not significant. We found a significant association between ADHD and oxidative stress that could not be accounted for by publication bias. The significant association lost significance after correcting for intrastudy clustering. No one observation accounted for the positive result. CONCLUSION: These results are preliminary given the small number of studies. They suggest that patients with ADHD have normal levels of antioxidant production, but that their response to oxidative stress is insufficient, leading to oxidative damage. PMID- 24232170 TI - Long-Term Memory Performance in Adult ADHD. AB - OBJECTIVE: Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. METHOD: We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. RESULTS: Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. CONCLUSION: Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented. PMID- 24232171 TI - Posterior reversible encephalopathy syndrome in a patient with a Chiari I malformation. AB - BACKGROUND: The authors describe a unique case of a patient who developed posterior reversible encephalopathy syndrome (PRES) following postoperative treatment of a Chiari I malformation. CASE DECSRIPTION: A 25-year-old female presented with complaints of left upper and lower extremity paresthesias and gait disturbances. A magnetic resonance imaging (MRI) of the brain and cervical spine showed a Chiari I malformation with tonsillar descent beyond the level of the C1 lamina. She underwent a suboccipital craniectomy and C1 laminectomy with cerebellar tonsillar cauterization and duraplasty. Postoperatively, an MRI showed bilateral acute infarcts of the cerebellar vermis. She was initially treated for cerebellar ischemia with hypertensive therapy with a subsequent decline in her neurologic status and generalized tonic-clonic seizure. Further workup showed evidence of PRES. After weaning pressors, the patient had a significant progressive improvement in her mental status. CONCLUSION: Although the mechanism of PRES remains controversial given its diverse clinical presentation, several theories implicate hypertension and steroid use as causative agents. PMID- 24232172 TI - Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking. AB - Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to relapse. Although activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking, its role in reinstatement-associated synaptic plasticity is not well characterized. Using rats extinguished from cocaine self administration, we found potentiated synaptic strength (assessed as the AMPA/NMDA current amplitude ratio) and increased spine head diameter in medium spiny neurons in the accumbens core (NAcore). The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced reinstatement. Two NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex (PL) and dopamine from the ventral tegmental area (VTA). Pharmacological inhibition of either PL or VTA prevented cocaine-primed reinstatement. However, inhibiting the PL further potentiated AMPA/NMDA and spine head diameter, while inactivating the VTA or the combined systemic administration of dopamine D1 and D2 antagonists prevented the increase in AMPA/NMDA and spine diameter induced by cocaine priming. These data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation in the NAcore during cocaine-induced reinstatement. Although activity in the PL was necessary for reinstatement, it inhibited synaptic potentiation initiated by an acute cocaine injection. Thus, although the PL and VTA differentially regulate the direction of synaptic plasticity induced by a cocaine-priming injection, coordinated synaptic potentiation by both NAcore afferents is necessary for cocaine-induced relapse. PMID- 24232173 TI - Long-term outcomes and quality of life after subtotal colectomy combined with modified Duhamel procedure for adult Hirschsprung's disease. AB - BACKGROUND: Subtotal colectomy combined with modified Duhamel procedure (Jinling procedure) was used in patients with adult Hirschsprung's disease (AHD) at Jinling Hospital in the last decade. The aim of this study is to evaluate the safety, effectiveness and quality of life of Jinling procedure for AHD. MATERIALS AND METHODS: All the data are from the database of the Jinling Hospital Constipation Registry System. Primary outcomes, including safety (morbidity and adverse events), effectiveness (satisfaction rate, Wexner constipation scale (WCS) and bowel function score (BFS)) and gastrointestinal quality of life index (GIQLI), were all evaluated. RESULTS: Fifty-nine patients were available for this study and the mean postoperative period was 44 months. Seventeen major complications were found in 11 patients and most of the complications could be managed conservatively. A significant improvement in WCS, BFS and GIQLI at 6 months postoperatively was obtained. CONCLUSION: Jinling procedure is safe and effective for AHD. PMID- 24232175 TI - Metabolism and elimination of N-ethyl-2-pyrrolidone (NEP) in human males after oral dosage. AB - N-Ethyl-2-pyrrolidone (NEP) is an industrial solvent that has been increasingly used to substitute N-methyl-2-pyrrolidone. NEP is under scrutiny in scientific and regulatory committees because of developmental toxic and teratogenic effects in rodents. The two postulated NEP metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5 HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) have recently been detected in urine samples from the general population. Thus, the toxicokinetic characterization of these biomarkers of NEP exposure in humans is of relevance both in the occupational as well as the environmental field. We orally dosed 20.9 mg NEP to three male volunteers. These volunteers collected all their urine samples over a period of 4 days post dose. In these samples we identified and quantified the above postulated NEP metabolites 5-HNEP and 2-HESI and determined their urinary elimination kinetics and their metabolic conversion factors. After 4 days we recovered 50.7 % of the dose as these two metabolites in urine, 29.1 % as 5-HNEP and 21.6 % as 2-HESI. The largest share of 5-HNEP was excreted within 24 h post dose, while the major share of 2-HESI was excreted on day 2 post dose. We estimated an elimination half-time for 5-HNEP of approx. 7 h and for 2-HESI of approx. 22-27 h. While the elimination of 5-HNEP was basically finished 72 h post dose, significant amounts of 2-HESI were still eliminated after 96 h. Both biomarkers can now be used in human biomonitoring studies to extrapolate from urinary measurements to the NEP dose taken up and thus to evaluate the risk caused by exposure to this chemical. PMID- 24232174 TI - Ideal timing of orchiopexy: a systematic review. AB - The ideal management of cryptorchidism is a highly debated topic within the field of pediatric surgery. The optimal timing of orchiopexy is particularly unclear, as existing literature reports mixed recommendations. The aim of this study was to determine, based on a systematic review, the most favorable age at which orchiopexy should be performed. We conducted a systematic search of MEDLINE, Embase, CINAHL, and the Cochrane Library to find relevant articles. Two researchers quality assessed each study using the following tools: AMSTAR (systematic reviews), Jadad (RCTs), and MINORS (non-RCTs). We developed a conclusion based on the highest quality studies. We found one relevant systematic review, one RCT, and 30 non-RCTs. Fertility potential was greatest when orchiopexy was performed before 1 year of age. Additionally, orchiopexy before 10 11 years may protect against the increased risk of testicular cancer associated with cryptorchidism. Orchiopexy should not be performed before 6 months of age, as testes may descend spontaneously during the first few months of life. The highest quality evidence recommends orchiopexy between 6 and 12 months of age. Surgery during this timeframe may optimize fertility potential and protect against testicular malignancy in children with cryptorchidism. PMID- 24232176 TI - The cytoprotective and the dark side of Nrf2. PMID- 24232177 TI - The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews. AB - AIMS: The aim of the study was to assess the cumulative evidence on the effectiveness of brief alcohol interventions in primary healthcare in order to highlight key knowledge gaps for further research. METHODS: An overview of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare published between 2002 and 2012. FINDINGS: Twenty-four systematic reviews met the eligibility criteria (covering a total of 56 randomized controlled trials reported across 80 papers). Across the included studies, it was consistently reported that brief intervention was effective for addressing hazardous and harmful drinking in primary healthcare, particularly in middle-aged, male drinkers. Evidence gaps included: brief intervention effectiveness in key groups (women, older and younger drinkers, minority ethnic groups, dependent/co-morbid drinkers and those living in transitional and developing countries); and the optimum brief intervention length and frequency to maintain longer-term effectiveness. CONCLUSION: This overview highlights the large volume of primarily positive evidence supporting brief alcohol intervention effects as well as some unanswered questions with regards to the effectiveness of brief alcohol intervention across different cultural settings and in specific population groups, and in respect of the optimum content of brief interventions that might benefit from further research. PMID- 24232178 TI - Alcohol screening and brief intervention for adolescents: the how, what and where of reducing alcohol consumption and related harm among young people. AB - AIM: The aim of the study was to explore the evidence base on alcohol screening and brief intervention for adolescents to determine age appropriate screening tools, effective brief interventions and appropriate locations to undertake these activities. METHODS: A review of existing reviews (2003-2013) and a systematic review of recent research not included in earlier reviews. RESULTS: The CRAFFT and AUDIT tools are recommended for identification of 'at risk' adolescents. Motivational interventions delivered over one or more sessions and based in health care or educational settings are effective at reducing levels of consumption and alcohol-related harm. CONCLUSION: Further research to develop age appropriate screening tools needs to be undertaken. Screening and brief intervention activity should be undertaken in settings where young people are likely to present; further assessment at such venues as paediatric emergency departments, sexual health clinics and youth offending teams should be evaluated. The use of electronic (web/smart-phone based) screening and intervention shows promise and should also be the focus of future research. PMID- 24232180 TI - Infarction of papillary thyroid carcinoma after fine-needle aspiration: case series and review of literature. AB - IMPORTANCE: Although infarction after fine-needle aspiration (FNA) is a rare occurrence, it is a known phenomenon that may lead to difficulties in interpretation for pathologists and in decision-making for head and neck surgeons. OBJECTIVE: To characterize our experience with infarction in papillary thyroid carcinomas (PTCs) after FNA and review existing cases of infarcted PTCs in the literature to better understand this phenomenon. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case series and review of literature at a tertiary medical center (University of California, Los Angeles [UCLA], Medical Center). All patients who had a surgical pathologic diagnosis of infarcted PTC and who underwent FNA prior to surgery at UCLA from June 2006 to June 2012 were identified. There were 620 cases of PTC and 12 cases of infarcted PTC. MAIN OUTCOMES AND MEASURE: Demographic data, FNA cytologic findings, and surgical pathologic data were gathered for each patient. A comprehensive literature search for infarcted PTC was performed. RESULTS: Twelve cases of infarcted PTC were found in a total of 620 cases of PTC (1.9%). The mean (SD) time interval between the last FNA and surgery was 52 (35) days (range, 13-133 days). All patients received a diagnosis of infarcted PTC after thyroidectomy was performed. Focal infarction was found in 4 patients (33%), and near-total infarction was found in 8 patients (67%). Five patients (47%) had the follicular variant of PTC, making it the most common subtype in our series. A thorough literature search yielded 11 articles reporting a total of 26 cases of infarcted PTC after FNA. To our knowledge, our case series on infarcted PTC is the largest reported series in the literature. CONCLUSIONS AND RELEVANCE: Although infarction of PTC after FNA occurs infrequently, it may lead to difficulties in histologic diagnosis. Awareness of this phenomenon and its histologic associations, along with careful reevaluation of the FNA and surgical specimens, is important for appropriate diagnosis and subsequent treatment. At this point, infarction in PTC should not alarm a head and neck surgeon to change management, but future prospective studies with a large population of patients with infarcted PTCs are needed to establish the impact of infarction on differences in treatment outcomes for therapies that may be used in PTCs. PMID- 24232179 TI - Parvovirus b19 associated hepatitis. AB - Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine. PMID- 24232181 TI - Chemically doped perylene diimide lamellae based field effect transistor with low operating voltage and high charge carrier mobility. AB - Chemical doping of an electron transporter results in the formation of a radical anion containing semiconductor which showed high electron mobility (13 cm(2) V( 1) s(-1)) at low operating voltage (1 V). PMID- 24232183 TI - EU-LIFE revives funding debate. A group of mid-level life science research institutes is reopening the debate on how to fund research at the EU level calling for a stronger emphasis on excellence. PMID- 24232182 TI - Cellular dynamics in the muscle satellite cell niche. AB - Satellite cells, the quintessential skeletal muscle stem cells, reside in a specialized local environment whose anatomy changes dynamically during tissue regeneration. The plasticity of this niche is attributable to regulation by the stem cells themselves and to a multitude of functionally diverse cell types. In particular, immune cells, fibrogenic cells, vessel-associated cells and committed and differentiated cells of the myogenic lineage have emerged as important constituents of the satellite cell niche. Here, we discuss the cellular dynamics during muscle regeneration and how disease can lead to perturbation of these mechanisms. To define the role of cellular components in the muscle stem cell niche is imperative for the development of cell-based therapies, as well as to better understand the pathobiology of degenerative conditions of the skeletal musculature. PMID- 24232184 TI - Complex diseases require complex therapies. PMID- 24232187 TI - Detection and significance of cytotoxic cell subsets in biopsies of HCV-infected human livers. AB - Chronic viral hepatitis C still remains the clinical challenge. Attempts of the immune system to cope with this infection are unsatisfactory. There is a conviction that the main site of interaction between virus (Hepatitis C virus, HCV) and immune system is in situ, i.e., in liver. Natural killer (NK) cells appeared relevant in the acute hepatitis. Less is known about the immune response in the chronic HCV infection. The aim of this study was to evaluate the prevalence of various cytotoxic cell subsets in chronic HCV+ liver tissue and to seek links between them and laboratory data of patients. Sections from paraffin blocks of liver biopsy tissues of HCV+ untreated patients were subjected to the reaction with antibodies vs. cytotoxic cell subsets and immunohistochemistry. Positive cells were searched in cellular infiltrates in portal areas and in liver parenchyma. They were classified on the "Yes" or "No" basis. Majority of liver biopsies exhibited cellular infiltrates in portal spaces and as single cells in liver parenchyma. Infiltrates consisted of CD8+ T cells, CD56+ NK ones, including CD158i+ and CD158b+. The latter were rarely seen. There were also granzyme B+ cells. The most abundant were NKG2D+ cells, much more common than NK CD56+ ones. It implied that NKG2D was also expressed on T cells. Prevalence of NKG2D+ cells correlated with high activity of liver enzymes such as alanine aminotransferase, aspartate aminotransferase and a greater histological severity of liver injury. NKG2D+ cells form the bulk of cells infiltrating HCV-infected human liver. Correlation of NKG2D+ cells with some laboratory parameters of patients suggests their role in hepatitis C pathogenesis. PMID- 24232186 TI - Building and remodelling Cullin-RING E3 ubiquitin ligases. AB - Cullin-RING E3 ubiquitin ligases (CRLs) control a plethora of biological pathways through targeted ubiquitylation of signalling proteins. These modular assemblies use substrate receptor modules to recruit specific targets. Recent efforts have focused on understanding the mechanisms that control the activity state of CRLs through dynamic alterations in CRL architecture. Central to these processes are cycles of cullin neddylation and deneddylation, as well as exchange of substrate receptor modules to re-sculpt the CRL landscape, thereby responding to the cellular requirements to turn over distinct proteins in different contexts. This review is focused on how CRLs are dynamically controlled with an emphasis on how cullin neddylation cycles are integrated with receptor exchange. PMID- 24232189 TI - Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4 sulfonatophenyl) porphyrin in an in vitro neuroblastoma model. AB - PURPOSE: Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4 sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. METHODS: Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS NPs (100 MUg/mL) and then to SWs (0.43 mJ/mm(2) for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. RESULTS: There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% +/- 3.89%) and apoptotic (27.45% +/- 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. CONCLUSION: The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment's efficacy in an in vitro neuroblastoma model. PMID- 24232185 TI - Three wise centromere functions: see no error, hear no break, speak no delay. AB - The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment. Two additional functions of the centromere, however, are becoming increasingly clear: facilitation of robust sister-chromatid cohesion at pericentromeres and advancement of replication of centromeric regions. The combination of these three centromere functions ensures correct chromosome segregation during mitosis. Here, we review the mechanisms of the kinetochore-microtubule interaction, focusing on sister-kinetochore bi orientation (or chromosome bi-orientation). We also discuss the biological importance of robust pericentromeric cohesion and early centromere replication, as well as the mechanisms orchestrating these two functions at the microtubule attachment site. PMID- 24232190 TI - Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology. AB - Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs. PMID- 24232191 TI - New and emerging pathogens in canine infectious respiratory disease. AB - Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings. PMID- 24232192 TI - Feasibility and preliminary efficacy of adding behavioral counseling to supervised physical activity in kidney cancer survivors: a randomized controlled trial. AB - BACKGROUND: Supervised physical activity (PA) improves short-term health outcomes in cancer survivors, but longer-term adherence is rarely achieved. OBJECTIVE: The aim of this study was to evaluate the feasibility and preliminary efficacy of adding behavioral counseling to supervised PA in kidney cancer survivors (KCSs). METHODS: Thirty-two KCSs were randomized to a 4-week supervised PA program plus standard exercise counseling (SPA + EC group; n = 16) or a 4-week supervised PA plus behavioral counseling based on the Theory of Planned Behavior (SPA + BC group; n = 16). The primary outcome was self-reported PA at 12 weeks. Secondary outcomes were quality of life, anthropometric measures, cardiorespiratory fitness, and physical function. RESULTS: Follow-up rates for outcomes at 12 weeks were 88% and 94% for fitness testing and questionnaires, respectively. Adherence to the interventions was 94% in both groups with a 6% attrition rate. Analyses of covariance revealed that PA minutes at 12 weeks favored the SPA + BC group by +34 minutes (95% confidence interval, -62 to 129), which was a small effect size (d = 0.21) not reaching statistical significance (P = .47). Moreover, the SPA + BC group increased their 6-minute walk by 48 m more than the SPA + EC group (95% confidence interval, 1-95; d = +0.64; P = .046). There were no significant changes in quality of life measures. CONCLUSIONS: This pilot study provides preliminary evidence that adding behavioral counseling to supervised PA in KCSs is feasible and may improve PA and fitness in the short-term. Larger and longer term trials are needed. IMPLICATIONS FOR PRACTICE: Oncology nurses may consider adopting behavioral counseling strategies in addition to supervised PA to motivate KCSs to maintain PA. PMID- 24232193 TI - Robotic Neuro-Endoscope with Concentric Tube Augmentation. AB - Surgical robots are gaining favor in part due to their capacity to reach remote locations within the body. Continuum robots are especially well suited for accessing deep spaces such as cerebral ventricles within the brain. Due to the entry point constraints and complicated structure, current techniques do not allow surgeons to access the full volume of the ventricles. The ability to access the ventricles with a dexterous robot would have significant clinical implications. This paper presents a concentric tube manipulator mated to a robotically controlled flexible endoscope. The device adds three degrees of freedom to the standard neuroendoscope and roboticizes the entire package allowing the operator to conveniently manipulate the device. To demonstrate the improved functionality, we use an in-silica virtual model as well as an ex-vivo anatomic model of a patient with a treatable form of hydrocephalus. In these experiments we demonstrate that the augmented and roboticized endoscope can efficiently reach critical regions that a manual scope cannot. PMID- 24232195 TI - Diversity and evolution of chloroplast DNA in Triticum and Aegilops as revealed by restriction fragment analysis. AB - Restriction fragment analysis of chloroplast (cp) DNAs from 35 wheat (Triticum) and Aegilops species, including their 42 accessions, was carried out with the use of 13 restriction enzymes to clarify variation in their cpDNAs. Fourteen fragment size mutations (deletions/insertions) and 33 recognition site changes were detected among 209 restriction sites sampled. Based on these results, the 42 accessions of wheat-Aegilops could be classified into 16 chloroplast genome types. Most polyploids and their related diploids showed identical restriction fragment patterns, indicating the conservatism of the chloroplast genome during speciation, and maternal lineages of most polyploids were disclosed. This classification of cpDNAs was principally in agreement with that of the plasma types assigned according to phenotypes arising from nucleus-cytoplasm interactions. These mutations detected by restriction fragment analysis were mapped on the physical map of common wheat cpDNA, which was constructed with 13 restriction endonucleases. Length mutations were more frequently observed in some regions than in others: in a 16.0 kilo base pairs (kbp) of DNA region, including rbcL and petA genes, 6 of 14 length mutations were concentrated. This indicates that hot spot regions exist for deletions/insertions in chloroplast genome. On the other hand, 33 recognition site mutations seemed to be distributed equally throughout the genome, except in the inverted repeat region where only one recognition site change was observed. Base substitution rate (p) of cpDNA was similar to that of other plants, such as Brassica, pea and Lycopersicon, showing constant base substitution rates among related taxa and slow evolution of cpDNA compared with animal mitochondrial DNA. Phylogenetic relationships among Triticum and Aegilops species were discussed, based on the present data. PMID- 24232194 TI - Likelihood of children with end-stage kidney disease in Europe to live with a functioning kidney transplant is mainly explained by nonmedical factors. AB - BACKGROUND: Registry data can be used to assess associations between medical and health-policy factors and the likelihood of children on renal replacement therapy (RRT) to live with a functioning kidney transplant in Europe. METHODS: A survey questionnaire was distributed among renal registry representatives in 38 European countries, and additional data was obtained from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry. RESULTS: Thirty-two countries with a pediatric RRT program responded. The median percentage of children by country on RRT with a functioning transplant was 62 % (interquartile range 39-77). One per million population increase in donation rate from deceased donors was associated with a 5 % increase in the percentage of functioning transplants; the existence of an intermediate and high pediatric priority policy doubled and tripled this percentage, respectively, compared with no priority, whereas an increase in living donor pediatric kidney transplant rate of one per million children was associated with a 14 % higher percentage of functioning transplants. The percentage of functioning transplants was also strongly associated with the gross domestic product (GDP). CONCLUSION: Considerable variations exist in the percentages of prevalent pediatric RRT populations with functioning renal transplants across Europe. A macroeconomic indicator such as GDP is the most important determinant of these international differences. Efforts should be made for living donation programs and pediatric allocation priority to increase access to kidney transplantation for children. PMID- 24232196 TI - Origin of chloroplast DNA diversity in the Andean potatoes. AB - Wide chloroplast DNA (ctDNA) diversity has been reported in the Andean cultivated tetraploid potato, Solanum tuberosum ssp. andigena. Andean diploid potatoes were analyzed in this study to elucidate the origin of the diverse ctDNA variation of the cultivated tetraploids. The ctDNA types of 58 cultivated diploid potatoes (S. stenotomum, S. goniocalyx and S. phureja), 35 accessions of S. sparsipilum, a diploid weed species, and 40 accessions of the wild or weed species, S. chacoense, were determined based on ctDNA restriction fragment patterns of BamHI, HindIII and PvuII. Several different ctDNA types were found in the cultivated potatoes as well as in weed and wild potato species; thus, intraspecific ctDNA variation may be common in both wild and cultivated potato species and perhaps in the higher plant kingdom as a whole. The ctDNA variation range of cultivated diploid potatoes was similar to that of the tetraploid potatoes, suggesting that the ctDNA diversity of the tetraploid potato could have been introduced from cultivated diploid potatoes. This provided further evidence that the Andean cultivated tetraploid potato, ssp. andigena, could have arisen many times from the cultivated diploid populations. The diverse but conserved ctDNA variation noted in the Andean potatoes may have occurred in the early stage of species differentiation of South American tuber-bearing Solanums. PMID- 24232197 TI - Gene differences in heading date, height, seed weight and seed yield between two pure line varieties of Triticum aestivum L. AB - Reciprocal sets of homozygous inbred backcross lines were developed by crossing two pure line varieties (Baart 46 and Ramona) of Triticum aestivum L., followed by two backcrosses to each of the two parent varieties, and six to eight generations of selfing. Data on each inbred backcross line was obtained from twelve plots (from replications in three years). Five genes were responsible for over 95% of the genetic variation for heading date. These genes had pleiotropic effects on plant height that were proportional to their effects on heading date. Two additional genes had detectable effects on plant height. The genes with a measurable effect on height accounted for 90% of the genetic variation in the Baart 46 genetic background. One gene affected seed weight. In the Ramona background, this gene accounted for 80% of the genetic variation in seed weight and 16% of the genetic variation in seed yield. Two genes, responsible for the earliest and latest heading date classes, had large pleiotropic effects on seed yield. They accounted for 60% of the genetic variation in yield. One gene, with no effect on heading date, caused a detectable reduction in yield of 23% in the Baart 46 inbred backcross lines. This gene had no apparent effect in the Ramona genetic background. Quantitative trait genes are sparsely distributed in the genome: fewer than one in four chromosome arms carries a gene with a detectable effect. Gene effects on quantitative traits are not small and similar. The distribution of 22 gene effects for heading date and height is slightly skewed to the right: as the magnitude of effect increases, the frequency of genes having the effect decreases. PMID- 24232198 TI - Factor and principal component analyses as alternatives to index selection. AB - Selections from factor and principal component analyses were compared with those from the Smith-Hazel index when selecting for several switchgrass (Panicum virgatum L.) traits. The objective of this study was to examine several alternatives to index selection. Such procedures would potentially eliminate problems of selection associated with Smith-Hazel indices, including errors in genetic parameter estimates and difficulty in assigning relative economic weights to traits. Selection was performed on 1,280 plants that were evaluated over 2 years at 1 location, in a randomized complete block design with 4 replicates. The plants were evaluated for forage yield and several forage quality traits. The comparisons of index selection with principal factor analysis, maximum-likelihood factor analysis and principal component analysis were made for three sets of traits (five traits per set) to estimate repeatability for the comparisons. Multivariate analyses were performed on both simple and genotypic correlation matrices. Comparisons were made by computing Spearman's rank correlations between selection index plant scores and scores computed from multivariate analysis and by determining the number of plants selected in common for the selection methods. Among the three multivariate analysis methods evaluated in this study, principal component analysis had the highest correlation with index selection. The high correlation for principal component analysis of simple correlation matrices indicates the potential for using this statistical method for selection purposes. This would permit the breeder to reduce field costs (e.g., time, labor, equipment) required to obtain the genetic parameter estimates necessary to construct selection indices. PMID- 24232199 TI - The measurement and analysis of competitive ability among populations of white clover and perennial ryegrass. AB - Analysis of the competitive interactions among a set of white clover and perennial ryegrass populations indicated that the intra-specific pressures exerted by the white clover plants upon themselves were significantly greater than the inter-specific pressures they exerted upon the perennial ryegrass. This partitioning of competitive effects could not be carried out on the ryegrass populations, however, because the data required the fitting of separate models to monocultures and duocultures. Although not significant at this stage of the experiment, trends were detected among some of the clover-ryegrass duocultures that could be related to their previous coexistence. The results are briefly discussed in relation to the problems surrounding the measurement of competitive effects among species that ideally require very different managements. PMID- 24232200 TI - Fractional paternity assignment: theoretical development and comparison to other methods. AB - There has recently been a burgeoning interest in the analysis of paternity patterns for natural populations because of its relevance to population genetic phenomena such as the distance between successful mates, relative male reproductive success and gene flow. In this paper we develop a method of analyzing populational patterns of paternity, the fractional paternity method, and compare its performance to two other commonly used methods of paternity analysis (simple exclusion and the most-likely methods). We show that the fractional method is the most accurate method for determining populational patterns of paternity because it assigns paternity to all progeny examined, and because it avoids biases inherent in the other paternity analysis methods when model assumptions are met. In particular, it avoids a systematic bias of the most likely paternity assignment method, which has a tendency to over-assign paternity of progeny to certain male parents with a greater than average number of homozygous marker loci. We also demonstrate the effect of linkage of some of the marker loci on paternity assignment, showing how the knowledge of the linkage phase of male and female parents in the population can significantly improve the accuracy of the estimates of populational patterns of paternity. Knowledge of the linkage phase of individuals in a population is usually unknown and difficult to assess without progeny testing, which involves considerable labor. However, we show how the linkage phase of hermaphroditic individuals in a population can be obtained in conjunction with the paternity analysis if progeny can be obtained from each hermaphroditic individual in the population, thereby avoiding the problem of traditional progeny testing. Applications of the fractional paternity approach developed herein should contribute significantly to our understanding of the mating patterns in, and hence the evolution of, natural populations. PMID- 24232201 TI - The effect of the etched (et) mutation on the amylolytic enzyme activities in germinating kernels and seedlings of Zea mays. AB - The etched (et) mutation in maize causes distinct depressions and structural gaps in the endosperm and also gives rise to virescent seedlings, alpha- and beta Amylase activities were observed to be higher in et (+) et (+) kernels and seedlings as compared to that of the et et mutant. The total amylase and beta amylase trends during germination also differed between normal and mutant kernels and seedlings (it increases in the wildtype and decreases in et et). On the contrary, the overall alpha-amylase trend was found to be similar in both genotypes (slight decrease during germination). The native gel electrophoresis of crude enzyme extracts did not reveal any qualitative differences in alpha and beta amylases during germination. The germinating et et kernels initially showed lower levels of starch compared with the wild type kernels, whereas no such difference was found at later stages of germination. It is concluded that et gene associated endosperm lesions lead to an impairment of starch degradation in germinating kernels resulting in virescent seedlings. PMID- 24232202 TI - Parametric and jackknife confidence interval estimators for two-factor mating design genetic variance ratios. AB - Confidence interval estimators have not been defined for dominance to additive genetic variance (theta) and average degree of dominance (delta) for the nested, factorial, and backcross mating designs. The objective of this paper was to describe interval estimators for these parameters. Approximate F random variables were defined for expected mean square (EMS) ratios for linear models with one environmental effect. Approximate 1-alpha parametric interval estimators were defined for theta and delta using these random variables. Random variables defined for linear models with no environmental effects are not approximately distributed as F random variables because common EMS are involved in the numerators and denominators of the EMS ratios. Delete-one jackknife (jackknife) interval estimators were defined for theta and delta for linear models with zero or one environmental effect(s); In transformed analysis of variance point estimates were used in pseudovalue estimators. PMID- 24232203 TI - The production of haploid wheat plants from wheat x maize crosses. AB - Hybrid embryos from hexaploid wheat x maize crosses rapidly lose the maize chromosomes to produce haploid wheat embryos. Such embryos almost always aborted when left to develop on the plant, and only 1 was recovered from 2440 florets (0.17% of the expected number). Embryos had greater viability in spikelet culture, 47 (26.5% of the expected number) being recovered from 706 ovaries. Thirty-two of these embryos germinated to give green plants, 31 of which were haploid (21 wheat chromosomes) and 1 of which was euploid (42 wheat chromosomes). Spikelet culture enabled 17.1% of the expected number of embryos to be recovered as haploid plants, a 100-fold improvement on allowing embryos to develop in vivo. Ten haploid plants of 'Chinese Spring' (kr1, kr2), 13 plants of 'Chinese Spring (Hope 5A)' (kr1, Kr2), and 8 of 'Hope' (Kr1, Kr2) were recovered. The potential of wheat x maize crosses for wheat haploid production and for gene transfer from maize to wheat is discussed. PMID- 24232204 TI - Isozyme marker loci associated with cold tolerance and maturity in maize. AB - Two maize (Zea mays L.) populations, AS1(S) and ECR-A, were evaluated for allozyme frequency changes associated with selection for improved seedling emergence, early season vigor and early maturity. Eleven marker loci were examined and four loci were used for indirect selection in an attempt to modify cold tolerance and maturity. Allozyme-selected divergent subpopulations were produced by compositing selected S1 progeny from cycle one (C1) of AS1(S) and from C2 of ECR-A. These subpopulations and S1 generations from all cycles resulting from phenotypic selection, ECR-A C1 through C7 and AS1(S) CO through C6, were tested in cold tolerance and agronomic performance trials over five environments in 1986. Seedling emergence and seedling dry weight did not improve with phenotypic selection in ECR-A, while plant height, ear height, grain yield, grain moisture, days to mid-silk and days to mid-pollen were reduced significantly. Contrasts between divergent allozyme-selected subpopulations from ECR-A were significant for grain moisture and mid-pollen date. For AS1(S), seeding emergence increased, while plant and ear height decreased with phenotypic selection. Contrasts between allozyme-selected subpopulations were significant for plant and ear height. Changes associated with marker-based selection for AS1(S) were not in the same direction as with phenotypic selection. Selection for favorable allozyme genotypes may be effective in changing certain traits in populations that have been modified by direct selection, however results may not be predictable. PMID- 24232205 TI - Genetic control of maternal haploidy in maize (Zea mays L.) and selection of haploid inducing lines. AB - The effect of genotype on maternal haploid plant production in maize was studied. The frequency of gynogenetic plants when "Stock 6" was used as pollinator varied according to the female parent genotype. No simple relation was observed between genotypic aptitudes for gynogenetic and androgenetic development, which occured after pollination of "W23" plant carrying the "indeterminate gametophyte" gene. Furthermore, the population NS, a favorably responsive genotype to anther culture, does not exhibit exceptional ability for in vivo gynogenesis. The effect of inbreeding and the influence of maternal haploid origin suggest that specific genes control maternal haploid initiation and development. However, gynogenetic development is not limited to a particular genotype. The frequency of maternal haploids may be increased by using specific pollen parents. Attempts were made to select for a high haploidyinducing trait and the present study reports the successful development of lines that can be utilized as pollen parents to induce haploids for experimental purposes and breeding programmes. When an inbred line "WS14", derived from the cross W23 x Stock 6, was used as pollen parent, 2%-5% maternal haploids were obtained according to the female parent genotype. A high haploidy-inducing potential is a heritable trait and may be controlled by a limited number of genes. Genetic determination of the haploidy-inducing character was examined in relation to the efficiency of the selecting method and the mechanisms involved in the origin of maternal haploids. PMID- 24232206 TI - Correlations between gametophytic (pollen) and sporophytic (seed) generations for polyunsaturated fatty acids in oilseed rape Brassica napus L. AB - Lipids were extracted from the diploid seed and haploid pollen of Brassica napus L. Two fractions of pollen lipids, namely the diploid-specified pollen-coat and the haploid-specified internal cytoplasmic lipids were obtained. Significant correlations exist between pollen and seed generations for linoleic (18?2) and linolenic (18?3) acids. In pollen internal storage lipids, the level of 18?3 is positively correlated and the level of 18?2 is negatively correlated with the level of 18?3 in seed lipids. Evidence is presented that strongly supports the hypothesis that lipid biosynthesis occurs within the pollen and that synthesis is specified by haploid genes. These data support the concept of pollen selection, so that selecting among living pollen grains for superior individuals has potential as a new plant breeding tool for improving seed oil quality. PMID- 24232207 TI - In situ hybridization to somatic metaphase chromosomes of potato. AB - An in situ hybridization procedure was developed for mitotic potato chromosomes by using a potato 24S rDNA probe. This repetitive sequence hybridized to the nucleolar organizer region (NOR) of chromosome 2 in 95%-100% of the metaphase plates. Another repetitive sequence (P5), isolated from the interdihaploid potato HH578, gave a "ladderpattern" in genomic Southern's of Solanum tuberosum and Solanum phureja, but not in those of Solanum brevidens and two Nicotiana species. This sequence hybridized predominantly on telomeric and centromeric regions of all chromosomes, although chromosomes 7, 8, 10 and 11 were not always labeled clearly. PMID- 24232208 TI - A method of analyzing cultivar x location x year experiments: a new stability parameter. AB - Assessment of cultivar performance in a cultivar x location x year experiment is often difficult because of the presence of a location x year interaction. Our objective is to demonstrate a method on separation of environment effects (location x year) into predictable and unpredictabel components. The analysis consists of two parts: (1) a regression analysis based on location effects (averaged over years), assuming that the location means represent predictable environmental variation; and (2) the estimation of stability (denoted type 4) based on the years within location mean squares, assuming that years within location represent unpredictable environmental variation. From the regression analysis in (1), a breeder can determine the optimum range of locations in which a cultivar is well suited, and from (2) he can choose the most stable cultivars. The advantage of type 4 stability is that it is independent of the other cultivars included in the test and of the regression coefficient estimated for predictable variation. Three sets of published data are used to illustrate the analysis. Type 4 stability is compared with type 3 stability (deviation mean square from regression on environmental index) for genetic consistency. The analyses suggest that type 4 stability is consistent and is therefore a potential genetic parameter, but type 3 stability is not. PMID- 24232209 TI - Variant mitochondrial protein and DNA patterns associated with cytoplasmic male sterile lines of Nicotiana. AB - Variation in mitochondrial protein synthesis and genome organization was investigated. Three different alloplasmic cytoplasmic male-sterile Nicotiana tabacum cultivars, carrying N. repanda, N. suaveolens or N. debneyi cytoplasm, were analysed together with corresponding male-fertile parental and restored material. Although several differences were detected in the proteins synthesized by isolated mitochondria from the male-sterile and male-fertile plants, most of these were related to the origin of the mitochondria. However, a 23 kD protein was synthesized in the male-sterile cultivar carrying N. debneyi mitochondria, but not in other lines containing this cytoplasm. This protein was also present in the male-fertile parent containing N. tabacum mitochondria. Only the enhanced production of a 30 kD protein in the lines carrying mitochondria from N. repanda or N. debneyi was exclusively correlated with CMS. This protein was not present in any of the corresponding male-fertile parental and restored lines. Restriction enzyme analysis of mitochondrial DNA revealed a difference in abundance of a 5.6 kb XhoI fragment between lines containing N. debneyi mitochondria. No rearrangements of mitochondrial DNA was found between male-fertile and male sterile lines carrying N. repanda or N. suaveolens cytoplasm. These results might indicate that CMS in alloplasmic Nicotiana cultivars is caused by alterations in the expression of mitochondrial genes, rather than by induced changes in the genome. PMID- 24232210 TI - Stability parameters and performance of interregional crosses in durum wheat (Triticum durum Desf.). AB - Twelve durum wheat varieties originating from 3 ecologically diverse regions and their 48 intergroup crosses were evaluated for stability of performance with respect to grain yield and certain component traits. The linear component of the genotype-environment interaction was revealed for grain yield, 100-grain weight and plant height, non-linear for tiller number whereas for grains per spike both components were equally important. However, except for tiller number, the linear component appeared to be contributing to a large extent towards the prevalent interactions. NP 404, Bijaga Yellow and Giorgio VZ 331 depicted stable performance for grain yield. However, considering all the attributes, the parents NP 404, Bijaga Yellow, Anhinga 's' and Mexicali 75 and hybrids NP 401 x Mexicali 75, NP 404 x Anhinga 's', NP 412 x Mexicali 75, NP 404 x Gerardo VZ 466 and Anhinga 's' x Capeiti appeared promising. The Mexican group as a whole exhibited a more stable performance than the other two evaluated groups. Compensating shift among the component characters was evident in the case of parents as well as hybrids and stability of performance appeared to be under genetic control. Effective utilization of these two aspects through introduction in otherwise desirable varieties has been advocated. PMID- 24232211 TI - Primary structure and sequence organization of the 16S-23S spacer in the ribosomal operon of soybean (Glycine max L.) chloroplast DNA. AB - The nucleotide sequence of a spacer region between 16S and 23S rRNA genes from soybean chloroplasts has been determined. The spacer region is over 3000 bp long and contains two tRNA genes, coding for rRNA(Ile) and tRNA(Ala) which contain intervening sequences of 953 and 811 base pairs respectively. There is a strong homology between the two introns suggesting that they have a common origin. These spacer tRNAs are synthesized as part of a kb precursor molecule containing 16S and 23S rRNA sequences. PMID- 24232212 TI - Inheritance and linkage relationships of glutamate oxaloacetate transaminase isoenzymes in apple : 2. The genes GOT-2 and GOT-4. AB - Independent dimeric genes GOT-2 and GOT-4 determining activity for glutamate oxaloacetate transaminase (E.C.2.6.1.1; GOT) in zones GOT-II and GOT-IV respectively were identified. Three alleles were found for GOT-2 and two for GOT 4, including a null allele for GOT-2 which produced detectable heterodimeric bands but not homodimeric bands. Linkage studies with leucine aminopeptidase (E.C.3.4.11.1; LAP) genes suggested linkage of GOT-2 with LAP-2 (r=0.13+/-0.23) and GOT-4 with LAP-1 (r=0.10+/-0.40). PMID- 24232213 TI - Attempts to detect extra genomial factors in cytoplasmic male-sterile petunia lines. AB - In the present study we examined the possibility that viruses, viroids or dsRNA are associated with cytoplasmic male sterile (cms) petunia. The assumption was made that if viruses or viroids were present, the treatments for elimination of viruses and viroids would produce "healthy" fertile plants. Male sterile plants were subjected to heat and cold treatments for 10 weeks and/ or for 5 months, after which apical meristems were isolated and cultured with the addition of antiviral factors. The mother plants, the regenerated plants and their progeny were sterile. These treatments did not affect sterility in sterile plants or the fertility of fertile plants. No dsRNA was found in cms petunia by gel electrophoresis. Thus, our data suggest that there are no viruses, viroids or dsRNA associated with cms petunia. Our data are in agreement with recent data, which suggests that the mitochondrial DNA is the site of the cytoplasmic male sterile gene in petunia. PMID- 24232214 TI - Inheritance of emergence time at low temperatures in segregating generations of maize. AB - North Carolina Design III and generation means analyses were used to study the inheritance of seedling emergence time and a related seedling growth parameter in crosses between 5-154, a line from CIMMYT Pool 5 with rapid seedling emergence under cool conditions, and two Corn Belt Dent lines of maize (Zea mays L.). The crosses were evaluated at low temperatures in controlled environment rooms. Additive genetic variances were larger than dominance variances in both crosses and estimates of the average levels of dominance were in the partial dominance range. Dominance was in the direction of rapid seedling emergence and rapid utilization of seed reserve. Estimates of minimum numbers of effective factors provided evidence for polygenic inheritance. PMID- 24232215 TI - Further approximations for selection intensity. AB - Three new approximations are suggested for the standardized selection intensity, i. Two are simple functions of powers of b, the fraction selected. These improve on previous approximations by covering a broader range of selection intensities. A third approximation is developed using a rational polynomial. This gave accurate approximation, but simplicity was lost. PMID- 24232216 TI - Divergent selection for in vitro developmental capacity of preimplantation mouse embryos. AB - Replicated divergent selection was conducted for two generations in ICR mice for in vitro developmental capacity (IVDC; percentage of fertilized one-cell zygotes developing to blastocysts in vitro per female donor). Realized heritabilities based on high and low selection were 0.03+/-0.08 and -0.11+/-0.09 in replicate 1, and 0.10+/-0.11 and 0.08+/-0.10 in replicate 2. No differences were detected between selection lines (P>0.2) or replicates (P>0.1). Estimate of heritability in the base population based on 332 daughter-dam pairs was 0.14+/-0.18. These results indicate that additive genetic variance contributes little to the phenotypic variance in this trait. Considerable phenotypic variation in IVDC was observed (mean=49.3; SD=31.0), with a range of IVDC from 0%-100%. Utilization of donor female as a blocking factor is suggested for designs of experiments with preimplantation embryos to increase precision and power of statistical analyses. PMID- 24232217 TI - Identification of a complete set of isogenic wheat/rye D-genome substitution lines by means of Giemsa C-banding. AB - A complete set of isogenic wheat/rye D-genome substitutions were produced by crossing an inbred line of spring rye Secale cereale L. cv. "Prolific" to a tetraploid wheat, the A-and B-genomes of which had previously been extracted from hexaploid wheat, Triticum aestivum L. em Thell. cv. "Thatcher". After chromosome doubling, the derived hexaploid triticale (x Triticosecale Wittmack) was backcrossed to 6x "Thatcher" and selection for wheat/rye substitution lines was carried out in BCF3 to BCF6 families by using Giemsa C-banding. Five fertile disomic wheat/rye D-genome substitution lines were obtained and their chromosomal constitution was determined to be 1D/1R, 2D/2R, 7D/4R, 6D/6R, 7D/7R. The two remaining 3R and 5R substitutions are at the moment in a monosomic condition. Another 1D/7R substitution was detected but this plant was very weak and sterile, indicating that only substitutions between homoeologous chromosomes result in fertile, vigorous plants. Furthermore, many rye telocentrics as well as rye-rye and rye-wheat translocations were selected. Since all lines selected in this program share the same genetic background of "Thatcher" wheat, genetic heterogeneity is excluded. The material is very useful, therefore, for analyzing the effects of different rye chromosomes or chromosome segments in an otherwise homozygous background. PMID- 24232218 TI - Interferon alpha with or without rituximab achieves a high response rate and durable responses in relapsed FL: 17 years' experience in a single centre. AB - Maintenance interferon alpha (IFN-alpha) immunotherapy after induction chemotherapy prolongs progression-free survival (PFS) in untreated follicular lymphoma (FL). Little information is available about IFN-alpha use in relapsed FL. This study aims to evaluate the benefit of IFN-alpha as a treatment of low burden FL relapse. This single-centre retrospective study identified 20 patients treated in 27 cases with IFN-alpha. We analysed all cases of IFN-alpha treatment in patients with low-burden FL in clinical relapse (11), partial response (5) or only with molecular minimal residual disease (MRD; 5). The treatment schedule was 3MIU IFN-alpha three times a week alone (16) or combined with four weekly rituximab (R; 11), according to the institution's policy. Except for the molecular relapses, responses were evaluated according to the IWG 1999 criteria. MRD was defined as a repeatedly detectable BCL2-IgH rearrangement in peripheral blood or bone marrow. In 22 cases of clinical relapses or partial responders, overall response rate was 68 %, with 55 % complete responses. Median PFS was 20.9 months (95 % confidence interval (95 % CI), 0-64.9) with 20.9 and 48.7 months in the IFN and R-IFN groups, respectively (p = 0.4). The median PFS of the five MRD cases was 133 months (95 % CI, 103-165). The Follicular Lymphoma International Prognostic Index score calculated at initiation of IFN-alpha treatment was predictive of time to relapse (p = 0.036). These results compare favourably with previous reports of the efficacy of R alone, and of R with IFN-alpha in relapse. Further research is required to explore the role of IFN-alpha in the management of FL. PMID- 24232219 TI - Label-free study of the function of ion channel protein on a microfluidic optical sensor integrated with artificial cell membrane. AB - A label-free optical sensor was constructed by integrating pH sensing material and supported phospholipid bilayers (SPBs) in a microfluidic chip. The pH sensing material was composed of a double layer structure consisting of chitosan hydrogel and electrochemically etched porous silicon. The pH change in the microchip could induce a reversible swelling of the chitosan hydrogel layer and consequently caused a shift in effective optical thickness (EOT) of the double layer, which could be observed by Fourier transformed reflectometric interference spectroscopy (FT-RIS). After phospholipid bilayers (PLBs) were self-assembled on the sensing layer, the EOT almost remained constant during the cycling of pH from 7.4 to 6.2, indicating the blockage of H(+) translocation by the PLBs. For studying the behavior of ion channel protein, gramicidin A, a typical ion channel protein, was inserted in the SPBs for mimicking the ion transportation function of cell membrane. Due to the H(+) transportation capability of gramicidin A, the optical response to pH change could partially recover. In the presence of Ca(2+), the pore of the ion channel protein was blocked, causing a significant decrease in the EOT response upon pH change. The bio-functionalized microfluidic sensor fabricated in this work will provide a reliable platform for studying the function of ion channel protein, which is an important class of drug targets. PMID- 24232220 TI - Effects of a clay mineral on microbial predation and parasitism ofEscherichia coli. AB - Montmorillonitic clay influences the biological control ofEscherichia coli in aquatic systems, the magnitude of the effects being dependent on the state of the clay and the type of host-antagonist interaction. The interaction ofBdellovibrio andE. coli was partially inhibited by the presence of montmorillonite. Because it is highly motile,Bdellovibrio apparently could penetrate any colloidal clay barrier aroundE. coli if the clay envelope was thin enough. Colloidal clay had little effect on predation ofE. coli by the myxobacteriumPolyangium, and had no effect on the activity of the amoebaVexillifera. Crude clay, on the other hand, resulted in a physical separation of predator and prey, and this completely inhibited theE. coli-Polyangium interaction and slowed the rate of engulfment ofE. coli byVexillifera.The interference of natural biological control by clays may alter the microbial balance favoring survival of fecal microorganisms and resulting in their accumulation in saline sediments. This could constitute a health hazard if these organisms were released by upwelling of bottom waters or were desorbed in estuarine systems by dilution during heavy rains. PMID- 24232221 TI - Comparison ofin Situ andin Vitro survival ofCandida albicans in seawater. AB - The survival in seawater of several laboratory and field isolates ofCandida albicans was investigated. Initial studies were madein vitro (flasks) to confirm previous reports. Frequent sampling of viable cells showed that flask experiments, even repeated, produced varied patterns of survival in this closed system. As an alternative, multiple experiments were run in untreated seawater in dialysis bags and plexiglas chambers at ambient temperature (17? to 22?C) in flowing seawater. Die-off rates of all cultures tested in dialysis bags were very rapid in the first day and may have been related to high levels of dissolved organic carbon in the tubing. Distilled water-or acid-washed bags did not yield significantly higher survival rates in all cases. When plexiglas chambers closed with Nuclepore membranes were used, survival rates decreased to 5% to 15% of the original population after 6 days. Chamber data were more uniform and represented approximately a twofold increase in survival over that shown previously inin vitro (flask) studies. Some evidence was obtained in all three test systems for the greater survival rate of a field isolate ofC. albicans compared with that noted for a laboratory (ATCC) strain. The results are considered to more accurately depict the survival ofC. albicans in summer temperate recreational waters. PMID- 24232222 TI - Microorganisms and heavy metal toxicity. AB - The environmental and microbiological factors that can influence heavy metal toxicity are discussed with a view to understanding the mechanisms of microbial metal tolerance. It is apparent that metal toxicity can be heavily influenced by environmental conditions. Binding of metals to organic materials, precipitation, complexation, and ionic interactions are all important phenomena that must be considered carefully in laboratory and field studies. It is also obvious that microbes possess a range of tolerance mechanisms, most featuring some kind of detoxification. Many of these detoxification mechanisms occur widely in the microbial world and are not only specific to microbes growing in metal contaminated environments. PMID- 24232223 TI - Effects of ingesting mercury-containing bacteria on mercury tolerance and growth rates of ciliates. AB - The ciliateUronema nigricans was found to acquire tolerance to mercury after being fed mercury-laden bacteria followed by exposure of washed suspensions of these ciliates to various concentrations of mercury in solution. Significant differences in percent mortality were observed for ciliates fed mercury-laden bacteria compared with control suspensions fed mercury-free bacteria. The phenomenon of acquired mercury tolerance was demonstrated within a single generation time. Ciliates fed mercury-free bacteria and subsequently exposed to increasing levels of mercury in solution showed an elevated tolerance to concentrations which, on initial testing, resulted in mortality of 83% of the ciliate population. The effect of ingesting mercury-laden bacteria on growth rate ofUronema was examined, and results showed no significant differences in growth rates of both 3- and 14-day-old cultures of protozoa that had been fed mercury laden and mercury-free bacteria under controlled conditions. PMID- 24232224 TI - Interactions between freshwater bacteria andAnkistrodesmus braunii in batch and continuous culture. AB - Batch and continuous cultures ofAnkistrodesmus braunii were established in an inorganic medium with growth rate limited by P. In batch culture, inoculation of lake water bacterial isolates ofPseudomonas sp. andFlavobacterium sp. showed that thePseudomonas isolate was capable of more rapid growth on algal exudates of lytic products than was theFlavobacterium isolate. When inoculated singly into a continuous culture (D=0.267 day(-1); P level, 2MUM), theFlavobacterium isolate initially caused a decrease in the population density of the alga, but then steady states for both organisms were obtained. ThePseudomonas isolate under the same conditions caused a rapid washout of the algal culture, and steady-state conditions were never obtained. When thePseudomonas isolate was added to the two member, steady-state system ofA. braunii andFlavobacterium, the algal population again washed out of the vessel, followed by theFlavobacterium and then thePseudomonas isolate. A transient increase in the P concentration to 200MUM in the culture vessel caused the low algal population level to increase, followed by increases in the bacterial isolates when the algal population was high enough to supply the required organic carbon source. The system demonstrated that competition for P between the alga and the bacteria can occur, and the results were dependent on the algal and bacterial relative growth rates. The bacterial growth rates were limited initially by organic substrates produced by the alga, and the different bacterial isolates competed for these substrates. PMID- 24232225 TI - Trophic interactions in soils as they affect energy and nutrient dynamics. I. Introduction. AB - The dynamics of nutrient transformations at the soil-root interface are complex but amenable to controlled experimental study. Using a conceptual model we introduce a series of papers which ascertain the role of microfloral-faunal trophic interactions in carbon, nitrogen, and phosphorus transformations in soil microcosms. PMID- 24232226 TI - Trophic interactions in soils as they affect energy and nutrient dynamics. II. Physiological responses of selected rhizosphere bacteria. AB - Comparative microbial functions in the plant root zone were studied by evaluating rhizosphere-derivedPseudomonas andArthrobacter growth in chemostat culture and responses to root-exudate-related nutrients after varied starvation periods. These organisms were chosen to represent zymogenous and autochthonous microbes, respectively. In chemostat culture, thePseudomonas isolate showed increased energy charge and decreased populations with higher growth rates, whereas theArthrobacter had lower energy charge and cell population values which did not change appreciably with growth rate. The responses of these two types of organisms also differed with starvation. ThePseudomonas lost its ability to respire efficiently in the presence of several known root exudate components, whereas theArthrobacter isolate, in comparison, maintained a lower but more consistent ability to utilize these nutrients with increased starvation. TheArthrobacter also showed increased utilization of several substrates after starvation, suggesting its potential ability to function under restricted nutrient availability conditions. These results suggest thatPseudomonas-type organisms in the rhizosphere may best function in periods of more intense exudate release, whereas organisms of theArthrobacter- type may be more efficient at nutrient utilization during periods of lesser nutrient flux. Based on these data the rhizosphere-derivedPseudomonas isolate was considered to be an appropriate bacterium to use in more complex rhizosphere microcosm experiments where nutrient flux dynamics would be emphasized. PMID- 24232227 TI - Trophic interactions in soils as they affect energy and nutrient dynamics. III. Biotic interactions of bacteria, amoebae, and nematodes. AB - Bacteria (Pseudomonas), amoebae (Acanthamoeba), and nematodes (Mesodiplogaster) were raised in soil microcosms with and without glucose additions. Nematode and amoebal grazing on bacteria significantly reduced bacterial populations by the end of a 24-day incubation period. Amoebal numbers decreased in the presence of nematodes with a corresponding increase in nematode numbers which reached a maximum of 230 nematodes/g of soil in the treatment with amoebae and glucose additions. After 24 days the nematode populations in the treatments without carbon additions were dominated by resistant dauer larvae indicating the unavailability of food. Although larval numbers were high in the treatments with glucose additions, the adult component of the population was still increasing at the end of the 24-day experiment. The effect of the presence of amoebae on nematode abundance was of the same magnitude as addition of 600MUg glucose-C. PMID- 24232228 TI - Trophic interactions in soils as they affect energy and nutrient dynamics. IV. Flows of metabolic and biomass carbon. AB - Flows of biomass and respiratory carbon were studied in a series of propylene oxide sterilized soil microcosms. One-half of the microcosms received three pulsed additions of 200 ppm glucose-carbon to mimic rhizosphere carbon inputs. Biotic variables were: bacteria (Pseudomonas) alone, or amoebae (Acanthamoeba) and nematodes (Mesodiplogaster) singly, or both combined in the presence of bacteria.Over the 24-day experiment, respiration was significantly higher in the microcosms containing the bacterial grazers. Biomass accumulation by amoebae was significantly higher than that by nematodes. The nematodes respired up to 30-fold more CO2 per unit biomass than did amoebae. Similar amounts of carbon flowed into both respiratory and biomass carbon in microcosms with fauna, compared with the bacteria-alone microcosms. However, partitioning of available carbon by the microfauna varied considerably, with little biomass production and relatively more CO2-C produced in the nematode-containing microcosms. The amoebae, in contrast, allocated more carbon to tissue production (about 40% assimilation efficiency) and correspondingly less to CO2. PMID- 24232229 TI - Trophic interactions in soils as they affect energy and nutrient dynamics. V. Phosphorus transformations. AB - Regeneration of nutrients from relatively nutrient-poor organic residues is essential for overall operation of an ecosystem. Nutrients thus released are, however, inadequate for the needs of the decomposer populations, and a much faster nutrient turnover involving bacterial immobilization and release occurs concurrently. Evidence from aquatic ecosystems indicates that bacteria release little phosphorus, for which they have high demand, whereas bacterial grazers play an important role in regeneration of bacterial phosphorus. Our studies extend these relationships to terrestrial ecosystems. We studied phosphorus immobilization and mineralization in soil incubations, simulating rhizospheres with combinations of bacterial, amoebal, and nematode populations. Bacteria quickly assimilated and retained much of the labile inorganic phosphorus as carbon substrates were metabolized. Most of this bacterial phosphorus was mineralized and returned to the inorganic phosphorus pool by the amoebae. Nematode effects on phosphorus mineralization were small, except for indirect effects on amoebal activity. The observed remineralization may reflect direct excretion by the amoebae, physiological effects on the bacterial populations, or both. These results suggest a major role of microfauna in nutrient cycling. PMID- 24232231 TI - An aqueous red emitting fluorescent fluoride sensing probe exhibiting a large Stokes shift and its application in cell imaging. AB - A novel red emitting fluorescent probe exhibiting a 143 nm Stokes shift for the detection of fluoride ions in an aqueous solution was developed. The probe displays a rapid response, high selectivity and good sensitivity towards F(-). Application of the probe for the selective detection of intracellular F(-) has been successfully demonstrated in living cells. PMID- 24232232 TI - Magnet(r) designation in Saudi Arabia: bridging cultures for nursing excellence. PMID- 24232233 TI - Healthcare reform: unprecedented opportunity, unparalleled risk. AB - This department column is devoted to posing insights about transitions through, to and from, administrative roles in nursing. The unprecedented challenges posed by healthcare reform present new and complex challenges for nurse executives. The author discusses transitions in thinking and approach that will be needed to respond to the challenges and keep the focus on nursing practice excellence and patient outcomes. PMID- 24232234 TI - Criteria for clinical information technology device selection: what do nurse executives need to know? AB - Hospital and healthcare's "most wired" organizations were surveyed to determine the evaluative criteria in the selection of bedside devices for clinical documentation. Ranked results of the characteristics are presented. Results can be used to inform nurse executives about selection criteria to consider. PMID- 24232235 TI - Crossing our quality chasm: continuing the case for graduate preparation of nurse managers and leaders. AB - The previous CGEAN Perspectives column compared the Baccalaureate Essentials document with American Nurses Credentialing Center (ANCC) and American Organization of Nurse Executives (AONE) certification examination content for nurse managers and concluded that the baccalaureate curriculum lacks the depth of content needed for today's frontline nurse leaders. This article continues the discussion by comparing the Master's Essentials document with ANCC and AONE nurse manager-level certification content to evaluate if a master's graduate education prepares nurses for the competencies of these management roles. PMID- 24232236 TI - Turnover, staffing, skill mix, and resident outcomes in a national sample of US nursing homes. AB - OBJECTIVES: The authors examined the relationship of staff turnover to selected nursing home quality outcomes, in the context of staffing and skill mix. BACKGROUND: Staff turnover is a serious concern in nursing homes as it has been found to adversely affect care. When employee turnover is minimized, better care quality is more likely in nursing homes. METHODS: Data from the National Nursing Home Survey, a nationally representative sample of US nursing homes, were linked to Nursing Home Compare quality outcomes and analyzed using logistic regression. RESULTS: Nursing homes with high certified nursing assistant turnover had significantly higher odds of pressure ulcers, pain, and urinary tract infections even after controlling for staffing, skill mix, bed size, and ownership. Nurse turnover was associated with twice the odds of pressure ulcers, although this was attenuated when staffing was controlled. CONCLUSIONS: This study suggests turnover may be more important in explaining nursing home (NH) outcomes than staffing and skill mix and should therefore be given greater emphasis. PMID- 24232237 TI - The effect of critical care nursing and organizational characteristics on pediatric cardiac surgery mortality in the United States. AB - OBJECTIVE: This study explored pediatric critical care nursing and organizational factors that impact in-hospital mortality for cardiac surgery patients across children's hospitals in the United States. BACKGROUND: Congenital heart disease is the most common birth defect and the no. 1 cause of death for infants with a congenital defect. Little is known about the impact of pediatric critical care nursing and organizational factors on pediatric mortality. METHODS: Nursing leaders from 38 children's hospitals that contribute data to the Pediatric Health Information System data set completed an organizational assessment for years 2009 and 2010. These data were linked with patient-level data. The Risk Adjustment for Congenital Heart Surgery method was used to adjust for baseline patient differences in patients younger than 18 years. RESULTS: The odds of death increased as the institutional percentage of pediatric critical care unit nurses with 2 years' clinical experience or less increased. The odds of mortality were highest when the percentage of RNs with 2 years' clinical experience or less was 20% or greater. The odds of death decreased as the institutional percentage of critical care nurses with 11 years' clinical experience or more increased and for hospitals participating in national quality metric benchmarking. Clinical experience was independently associated with in-hospital mortality. CONCLUSIONS: These data are the 1st to link clinical nursing experience with pediatric patient outcomes. A cut point of 20% RNs or greater with 2 years' clinical experience or less was determined to significantly affect inpatient mortality. Participation in national quality metric benchmarking programs was significantly associated with improved mortality. PMID- 24232239 TI - Nurse-physician leadership: insights into interprofessional collaboration. AB - OBJECTIVE: The objective of this qualitative research study was to identify themes characterizing collaboration from the perspectives of nurses and physicians serving in complementary leadership roles in intensive and progressive care hospital units. BACKGROUND: Failures of communication are reported as a major cause of sentinel events. Most frequently, communication breakdown occurs between physicians and nurses. METHODS: In this qualitative research study, taped interviews with nursing and medical unit directors (physicians) were analyzed for themes regarding factors influencing collaboration. RESULTS: Themes identified included the impact of organizational support, shared expectations, relationships, and communication. CONCLUSIONS: Findings of this study support the need for organizations and professionals to facilitate deliberate, structured interprofessional communication to advance collaboration between nurses and physicians. PMID- 24232238 TI - Identification of potential barriers to nurse-sensitive outcome demonstration. AB - OBJECTIVE: The objective of this study was to determine differences in chief nursing officer, Magnet((r)) program director, nurse leader, and direct care RN perspectives of potential barriers to demonstration of nurse-sensitive outcomes. BACKGROUND: The Magnet Recognition Program((r)) and other designations are focusing on patient outcomes. No evidence is available addressing barriers to demonstration of nursing outcomes at multiple levels of practice. METHODS: A Likert scale tool was developed and administered to 526 attendees at the 2012 national Magnet conference. Questions related to available resources, benchmarks, outcome demonstration process understanding, perception of value, and competing priorities. RESULTS: Significant perception differences by role were demonstrated related to available resources, competing priorities, and process understanding supporting demonstration of nurse-sensitive outcomes. No significant differences were identified related to benchmarks or perception of process value to the organization. CONCLUSION: This study provides new information demonstrating potential barriers to demonstration of nurse-sensitive outcomes differing by role. Opportunity exists to develop systems and processes to reduce perceived barriers among the nursing workforce. PMID- 24232240 TI - Participating in a multihospital study to promote adoption of heart failure guidelines: lessons for nurse leaders. AB - Many multisite studies in practice settings focus on improving processes of care, adopting evidence-based practices, and improving patient outcomes. While specific research questions may be the focus, it is the implementation issues and strategies that reveal how individuals and organizations are profoundly transformed. Utilizing voluntary testimonies and conversations with participating nurses, the benefits of involvement in a multisite study extend beyond meeting Magnet((r)) research requirements. PMID- 24232241 TI - Work engagement in Magnet((r))-designated hospitals: Exploring social and institutional demographics of RNs to optimize improvement efforts. AB - OBJECTIVE: This study analyzed and evaluated relationships between work engagement (WE) and social/institutional demographic variables of RNs in Magnet((r))-designated hospitals. BACKGROUND: Organizational structures of Magnet designated hospitals are recognized to promote engagement of RNs. Because little is known about relationships between WE and the social/institutional demographics of nurses, this study focused on age (generation), gender, education, shift, hours worked per week, percentage of time in direct patient care, and nursing unit. METHODS: A convenience sample of hospital RNs (n = 220) completed 2 surveys to measure WE and demographic variables in this descriptive correlational study. RESULTS: Shift was significantly related to RN engagement; however, age, gender, education, hours worked per week, percentage of time in direct patient care, and nursing unit were not. CONCLUSIONS: This study provides empirical evidence about the relationships between WE and social/institutional characteristics of RNs. The findings are relevant to patients, nurses, nurse leaders, and organizations. PMID- 24232242 TI - Measuring first-line nurse manager work: instrument: development and testing. AB - OBJECTIVE: The objective of this study was to develop and test a 1st-line nurse manager (FLNM) work instrument to measure categories of work and frequency of activities. BACKGROUND: First-line nurse managers have been demonstrated to be key contributors in meeting organizational outcomes and patient and nurse satisfaction. Identifying the work of FLNMs is essential to help in the development of prioritization and sequence. The need for an instrument that can measure and categorize the work of FLNMs is indicated. METHODS: The author developed instrument was administered as a pilot study to 173 FLNMs in New Jersey. Descriptive statistics were analyzed, and validity and reliability were measured. RESULTS: Content validity was established through 2 focus groups using 10 FLNMs and conducting a survey of 5 chief nursing officers. Reliability was assessed by 13 of 16 FLNM participants using the test/retest method and quantified using percent agreement within a 10-day period. Those items with 70% agreement or more were identified as reliable and retained on the instrument. CONCLUSIONS: The content validity of the instrument is strong; further refinement and testing of the tool are indicated to improve the reliability and generalizability across multiple populations of leaders and settings. PMID- 24232244 TI - Pediatric traumatic brain injuries treated with decompressive craniectomy. AB - BACKGROUND: Traumatic brain injury (TBI) occurs in an estimated 80% of all pediatric trauma patients and is the leading cause of death and disability in the pediatric population. Decompressive craniectomy is a procedure used to decrease intracranial pressure by allowing the brain room to swell and therefore increase cerebral perfusion to the brain. METHODS: This is a retrospective study done at St. Mary's Medical Center/Palm Beach Children's Hospital encompassing a 3 year 7 month period. All the pediatric patients who sustained a TBI and who were treated with a decompressive craniectomy were included. The patients' outcomes were monitored and scored according to the Rancho Los Amigos Score at the time of discharge from the hospital and 6 months postdischarge. RESULTS: A total of 379 pediatric patients with a diagnosis of TBI were admitted during this time. All these patients were treated according to the severity of their injury. A total of 49 pediatric patients required neurosurgical intervention and 7 of these patients met the criteria for a decompressive craniectomy. All seven patients returned home with favorable outcomes. CONCLUSION: This study supports the current literature that decompressive craniectomy is no longer an intervention used as a last resort but an effective first line treatment to be considered. PMID- 24232245 TI - Spectral asymmetry and Higuchi's fractal dimension measures of depression electroencephalogram. AB - This study was aimed to compare two electroencephalogram (EEG) analysis methods, spectral asymmetry index (SASI) and Higuchi's fractal dimension (HFD), for detection of depression. Linear SASI method is based on evaluation of the balance of powers in two EEG frequency bands in one channel selected higher and lower than the alpha band spectrum maximum. Nonlinear HFD method calculates fractal dimension directly in the time domain. The resting EEG signals of 17 depressive patients and 17 control subjects were used as a database for calculations. SASI values were positive for depressive and negative for control group (P < 0.05). SASI provided the true detection rate of 88% in the depressive and 82% in the control group. The calculated HFD values detected a small (3%) increase with depression (P < 0.05). HFD provided the true detection rate of 94% in the depressive group and 76% in the control group. The rate of correct indication in the both groups was 85% using SASI or HFD. Statistically significant variations were not revealed between hemispheres (P > 0.05). The results indicated that the linear EEG analysis method SASI and the nonlinear HFD method both demonstrated a good sensitivity for detection of characteristic features of depression in a single-channel EEG. PMID- 24232246 TI - Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. AB - The objective of this prospective, multicentre, non-controlled, open-label study was to evaluate the effects of an iodine-restricted food on circulating total thyroxine (TT4) concentrations and clinical parameters in client-owned cats with hyperthyroidism. Two hundred and twenty-five cats were enrolled in the study and adapted to the iodine-restricted food. Data from physical examinations, questionnaires completed by veterinarians and owners, and circulating concentrations of TT4, urea and creatinine were recorded at weeks 0, 4 and 8. The study group included 136 female and 89 male cats (median age 15 years, range 4-21 years). Group 1 (n = 113) had been on previous anti-thyroid medication, while group 2 (n = 112) consisted of newly diagnosed cats. No differences were found between the two groups at any time point. Circulating TT4 concentrations had decreased (P <0.0001) at week 4 and did not change significantly from week 4 to week 8. Circulating TT4 concentration was within the reference range in 56/88 cats at week 4 and in 51/68 cats at week 8. Clinical parameters (vomiting, polyuria, polydipsia, hyperactivity, polyphagia, weight loss, hair coat quality, and quality of life) had improved (P <0.0001) by week 4. Circulating creatinine concentration decreased (P = 0.001) from week 0 to week 4. Side effects associated with feeding the iodine-restricted food were not observed. In conclusion, in client-owned cats with hyperthyroidism an iodine-restricted food is a valuable management option to normalise circulating TT4 concentrations, and improve clinical signs of hyperthyroidism within 4 weeks. This applies to newly diagnosed cats, as well as to previously diagnosed cats receiving anti-thyroid drugs. PMID- 24232248 TI - Genome-wide chromatin analysis in mature mouse and human spermatozoa. AB - At the end of mammalian spermatogenesis, chromatin in differentiating germ cells is extensively remodeled, with the majority of nucleosomes being removed and ultimately exchanged by highly basic proteins named protamines. Residual nucleosomes are, to various degrees, retained at regulatory sequences in human and mouse sperm. Moreover, certain histone variants and modifications remain present in regulatory sequences of subsets of genes in spermatozoa, providing opportunities for paternal inheritance of chromatin states and epigenetic control of gene expression in the subsequent generation. Here we describe in detail a method that enables the generation of soluble chromatin samples from mouse and human spermatozoa within 1 d. These samples are amendable to chromatin immunoprecipitation and high-throughput sequencing of nucleosome-associated genomic DNA, which require several additional days. We also provide computational scripts that allow straightforward analysis of large genome-wide data sets by biologists with limited computational experience. This protocol will facilitate studies of mechanisms of chromatin remodeling and epigenetic reprogramming during spermatogenesis and of paternal epigenetic inheritance. Similarly, it will help in the study of the causes of human male infertility. PMID- 24232249 TI - In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture. AB - It is useful to be able to grow enriched populations of stem cells in vitro. Growth of stem cells as tissue spheroids is a key methodology permitting sustainable culture of adult epithelial cells. Gastrointestinal stem cells can be propagated by using conditioned medium from a supportive cell line (L-WRN). This protocol describes how to prepare conditioned medium and how to culture stem cell enriched epithelial spheroids from the mouse gastrointestine. These spheroids are also amenable to genetic modification with recombinant lentiviruses. This system enables many types of cell biological assays that have been performed with immortalized cell lines to be applied to spheroids. Isolation of epithelial cell units from mice takes up to 2 h, and stem cell-enriched gastrointestinal spheroids are obtained within 3 d. Genetically modified spheroids with lentiviruses can be obtained in 2 weeks. PMID- 24232250 TI - Chemical synthesis of proteins using peptide hydrazides as thioester surrogates. AB - This protocol provides a detailed procedure for the chemical synthesis of proteins through native chemical ligation of peptide hydrazides. The two crucial stages of this protocol are (i) the solid-phase synthesis of peptide hydrazides via Fmoc chemistry and (ii) the native chemical ligation of peptide hydrazides through in situ NaNO2 activation and thiolysis. This protocol may be of help in the synthesis of proteins that are not easily produced by recombinant technology and that include acid-sensitive modifications; it also does not involve the use of hazardous HF. The utility of the protocol is shown for the total synthesis of 140-aa-long alpha-synuclein, a protein that has an important role in the development of Parkinson's disease. The whole synthesis of the target protein alpha-synuclein in milligram scale takes ~30 working days. PMID- 24232251 TI - Whole-mount immunostaining of Drosophila skeletal muscle. AB - Skeletal muscle undergoes marked functional decay during aging in humans, but the cell biological mechanisms responsible for this process are only partly known. Age-related muscle dysfunction is also a feature of aging in the fruit fly Drosophila melanogaster. Here we describe a detailed step-by-step protocol, which takes place over 3 d, for whole-mount immunostaining of Drosophila flight muscle. The skeletal muscle is fixed and permeabilized without any tissue freezing and dehydration so that antigens are accessible for staining with appropriate antibodies and the overall tissue ultrastructure is well preserved. This technique can be used to identify age-related cellular changes driving skeletal muscle aging and for characterizing models of human muscle disease in Drosophila. PMID- 24232252 TI - Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats. AB - The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke. PMID- 24232253 TI - Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. AB - Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications. PMID- 24232254 TI - Developmental changes in hematopoietic stem cell properties. AB - Hematopoietic stem cells (HSCs) comprise a rare population of cells that can regenerate and maintain lifelong blood cell production. This functionality is achieved through their ability to undergo many divisions without activating a poised, but latent, capacity for differentiation into multiple blood cell types. Throughout life, HSCs undergo sequential changes in several key properties. These affect mechanisms that regulate the self-renewal, turnover and differentiation of HSCs as well as the properties of the committed progenitors and terminally differentiated cells derived from them. Recent findings point to the Lin28b-let-7 pathway as a master regulator of many of these changes with important implications for the clinical use of HSCs for marrow rescue and gene therapy, as well as furthering our understanding of the different pathogenesis of childhood and adult-onset leukemia. PMID- 24232255 TI - Very small embryonic-like stem-cell optimization of isolation protocols: an update of molecular signatures and a review of current in vivo applications. AB - As the theory of stem cell plasticity was first proposed, we have explored an alternative hypothesis for this phenomenon: namely that adult bone marrow (BM) and umbilical cord blood (UCB) contain more developmentally primitive cells than hematopoietic stem cells (HSCs). In support of this notion, using multiparameter sorting we were able to isolate small Sca1(+)Lin(-)CD45(-) cells and CD133(+)Lin( )CD45(-) cells from murine BM and human UCB, respectively, which were further enriched for the detection of various early developmental markers such as the SSEA antigen on the surface and the Oct4 and Nanog transcription factors in the nucleus. Similar populations of cells have been found in various organs by our team and others, including the heart, brain and gonads. Owing to their primitive cellular features, such as the high nuclear/cytoplasm ratio and the presence of euchromatin, they are called very small embryonic-like stem cells (VSELs). In the appropriate in vivo models, VSELs differentiate into long-term repopulating HSCs, mesenchymal stem cells (MSCs), lung epithelial cells, cardiomyocytes and gametes. In this review, we discuss the most recent data from our laboratory and other groups regarding the optimal isolation procedures and describe the updated molecular characteristics of VSELs. PMID- 24232256 TI - In situ tissue regeneration through host stem cell recruitment. AB - The field of tissue engineering has made steady progress in translating various tissue applications. Although the classical tissue engineering strategy, which involves the use of culture-expanded cells and scaffolds to produce a tissue construct for implantation, has been validated, this approach involves extensive cell expansion steps, requiring a lot of time and laborious effort before implantation. To bypass this ex vivo process, a new approach has been introduced. In situ tissue regeneration utilizes the body's own regenerating capacity by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the site of injury. This approach relies on development of a target-specific biomaterial scaffolding system that can effectively control the host microenvironment and mobilize host stem/progenitor cells to target tissues. An appropriate microenvironment provided by implanted scaffolds would facilitate recruitment of host cells that can be guided to regenerating structural and functional tissues. PMID- 24232257 TI - Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands. AB - Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland. PMID- 24232258 TI - Implications and limitations of cellular reprogramming for psychiatric drug development. AB - Human-induced pluripotent stem cells (hiPSCs) derived from somatic cells of patients have opened possibilities for in vitro modeling of the physiology of neural (and other) cells in psychiatric disease states. Issues in early stages of technology development include (1) establishing a library of cells from adequately phenotyped patients, (2) streamlining laborious, costly hiPSC derivation and characterization, (3) assessing whether mutations or other alterations introduced by reprogramming confound interpretation, (4) developing efficient differentiation strategies to relevant cell types, (5) identifying discernible cellular phenotypes meaningful for cyclic, stress induced or relapsing-remitting diseases, (6) converting phenotypes to screening assays suitable for genome-wide mechanistic studies or large collection compound testing and (7) controlling for variability in relation to disease specificity amidst low sample numbers. Coordination of material for reprogramming from patients well characterized clinically, genetically and with neuroimaging are beginning, and initial studies have begun to identify cellular phenotypes. Finally, several psychiatric drugs have been found to alter reprogramming efficiency in vitro, suggesting further complexity in applying hiPSCs to psychiatric diseases or that some drugs influence neural differentiation moreso than generally recognized. Despite these challenges, studies utilizing hiPSCs may eventually serve to fill essential niches in the translational pipeline for the discovery of new therapeutics. PMID- 24232260 TI - Stem cell implantation for osteonecrosis of the femoral head. AB - What is the most effective treatment for the early stages of osteonecrosis of the femoral head? We assessed multiple drilling and stem cell implantation to treat the early stages of osteonecrosis of the femoral head. We report the clinical and radiological results of stem cell implantation and core decompression. In total, 128 patients (190 hips) who had undergone surgery were divided into two groups based on which treatment they had received: (1) multiple drilling and stem cell implantation or (2) core decompression, curettage and a bone graft. The clinical and radiographic results of the two groups were compared. At 5-year follow-up, in the stem cell implantation group, 64.3% (27/42) of the patients with Stage IIa disease, 56.7% (21/37) of the patients with Stage IIb disease and 42.9% (21/49) of the patients with Stage III disease had undergone no additional surgery. In the conventional core decompression group, 64.3% (9/14) of the patients with Stage IIa disease, 55.6% (5/9) of the patients with Stage IIb disease and 37.5% (3/8) of the patients with Stage III disease had undergone no additional surgery. Success rates were higher in patients with Ficat Stage I or II lesions than in those with Stage III lesions. There were no statistically significant differences between the groups in terms of success rate or in the clinical and radiographic results of the two methods. Essentially the same results were found with stem cell implantation as with the conventional method of core decompression. PMID- 24232259 TI - Amyloid-beta oligomers regulate the properties of human neural stem cells through GSK-3beta signaling. AB - Alzheimer's disease (AD) is the most common cause of age-related dementia. The neuropathological hallmarks of AD include extracellular deposition of amyloid beta peptides and neurofibrillary tangles that lead to intracellular hyperphosphorylated tau in the brain. Soluble amyloid-beta oligomers are the primary pathogenic factor leading to cognitive impairment in AD. Neural stem cells (NSCs) are able to self-renew and give rise to multiple neural cell lineages in both developing and adult central nervous systems. To explore the relationship between AD-related pathology and the behaviors of NSCs that enable neuroregeneration, a number of studies have used animal and in vitro models to investigate the role of amyloid-beta on NSCs derived from various brain regions at different developmental stages. However, the Abeta effects on NSCs remain poorly understood because of conflicting results. To investigate the effects of amyloid-beta oligomers on human NSCs, we established amyloid precursor protein Swedish mutant-expressing cells and identified cell-derived amyloid-beta oligomers in the culture media. Human NSCs were isolated from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres. Human NSCs exposure to cell-derived amyloid-beta oligomers decreased dividing potential resulting from senescence through telomere attrition, impaired neurogenesis and promoted gliogenesis, and attenuated mobility. These amyloid beta oligomers modulated the proliferation, differentiation and migration patterns of human NSCs via a glycogen synthase kinase-3beta-mediated signaling pathway. These findings contribute to the development of human NSC-based therapy for AD by elucidating the effects of Abeta oligomers on human NSCs. PMID- 24232261 TI - Negative-pressure wound therapy induces endothelial progenitor cell mobilization in diabetic patients with foot infection or skin defects. AB - Non healing chronic wounds are difficult to treat in patients with diabetes and can result in severe medical problems for these patients and for society. Negative-pressure wound therapy (NPWT) has been adopted to treat intractable chronic wounds and has been reported to be effective. However, the mechanisms underlying the effects of this treatment have not been elucidated. To assess the vasculogenic effect of NPWT, we evaluated the systemic mobilization of endothelial progenitor cells (EPCs) during NPWT. Twenty-two of 29 consecutive patients who presented at the clinic of Seoul National Universty Hospital between December 2009 and November 2010 who underwent NPWT for diabetic foot infections or skin ulcers were included in this study. Peripheral blood samples were taken before NPWT (pre-NPWT) and 7-14 days after the initiation of NPWT (during-NPWT). Fluorescence-activated cell sorting (FACS) analysis showed that the number of cells in EPC-enriched fractions increased after NPWT, and the numbers of EPC colony forming units (CFUs) significantly increased during NPWT. We believe that NPWT is useful for treating patients with diabetic foot infections and skin ulcers, especially when these conditions are accompanied by peripheral arterial insufficiency. The systemic mobilization of EPCs during NPWT may be a mechanism for healing intractable wounds in diabetic patients with foot infections or skin defects via the formation of increased granulation tissue with numerous small blood vessels. PMID- 24232262 TI - Special feature on stem cells: current research and future prospects. PMID- 24232263 TI - Interleukin-4 and acetaminophen hepatotoxicity: a story of conflicting results and conclusions. PMID- 24232264 TI - Structure and variability of nuclear ribosomal genes in the genus Helianthus. AB - The restriction map of the rDNA unit of Helianthus annuus was constructed using EcoRI, BamHI, HindIII, KpnI and SacI restriction enzymes. Variations in this map among 61 ecotypes representing 39 species of the genus Helianthus were analyzed. The sizes of the rDNA unit ranged from 9.8 to 11.0 kbp, due to a length-repeat heterogeneity of the external non-transcribed spacer by increments of 200 base pair segments. Lengthrepeat heterogeneity and restriction polymorphism were found to be characteristic of populations or species of Helianthus. Restriction patterns and thermal melting with probes of a cloned H. annuus ENTS segment allowed us to differentiate species from each other. However, most lines of the cultivated sunflower were found to be identical on the basis of the physical properties of their ribosomal DNA. PMID- 24232265 TI - Interspecific somatic hybrid plants between eggplant (Solanum melongena) and Solanum torvum. AB - Mesophyll protoplasts of eggplant (cv Black Beauty) and of Solanum torvum (both 2n=2x=24) were fused using a modification of the Menczel and Wolfe PEG/DMSO procedure. Protoplasts post-fusion were plated at 1 * 10(5)/ml in modified KM medium, which inhibited division of S. torvum protoplasts. One week prior to shoot regeneration, ten individual calluses had a unique light-green background and were verified as cell hybrids by the presence of the dimer isozyme patterns for phosphoglucoisomerase (PGI) and glutamate oxaloacetate transaminase (GOT). Hybridity was also confirmed at the plant stage by DNA-DNA hybridization to a pea 45S ribosomal RNA gene probe. The ten somatic hybrid plants were established in the greenhouse and exhibited intermediate morphological characteristics such as leaf size and shape, flower size, shape, color and plant stature. Their chromosome number ranged from 46-48 (expected 2n=4x=48) and pollen viability was 5%-70%. In vitro shoots taken from the ten hybrid plants exhibited resistance to a verticillium wilt extract. Total DNA from the ten hybrids was restricted and hybridized with a 5.9 kb Oenothera chloroplast cytochrome f gene probe, a 2.4 kb EcoRI clone encoding mitochondrial cytochrome oxidase subunit II from maize and a 22.1 kb Sal I mitochondrial clone from Nicotiana sylvestris. Southern blot hybridization patterns showed that eight of ten somatic hybrids contained the eggplant cpDNA, while two plants contained the cpDNA hybridization patterns of both parents. The mtDNA analysis revealed the presence of novel bands, loss of some specific parental bands and mixture of specific bands from both parents in the restriction hybridization profiles of the hybrids. PMID- 24232266 TI - Application of interspecific sesquiploidy to introgression of PLRV resistance from non-tuber-bearing Solanum etuberosum to cultivated potato germplasm. AB - Hybridization of synthetic allotetraploids of S. pinnatisectum with S. etuberosum (4x-EP) with S. acaule (2n = 4x = 48) resulted in two individuals that were highly fertile, in contrast to all other progenies. The unique individuals are hexaploids, 2n = 72, while the other progenies are tetraploids, 2n = 48. They are thought to be the products of a union between 2n eggs of S. acaule and normal 1n microspores of 4x-EP. The fertile hexaploids (designated 6x-AEP) produced abundant selfed seed and viable hybrids with cultivated diploid potato, S. phureja, when developing embryos were rescued from berries and cultured before transplanting to pot culture. The extreme variability in chromosome constitution of the hybrids with S. phureja and selfed progenies indicates that addition and substitution lines of etb chromosomes bearing genes of interest to breeders could easily be produced from this material. The production of sesquiploids, as the 6x AEP hybrids are called, is discussed as a useful bridging step in the introduction of alien genes from genomes that share little homology with the cultivated genome. PMID- 24232267 TI - Enhancement of somatic embryogenesis in Norway spruce (Picea abies L.). AB - Embryogenic callus developed in 55% of the mature embryo explants of Norway spruce (Picea abies L.) growing on a LP medium minus the amino acids and sugars (except sucrose). This is the highest reported yield of embryogenic callus from mature embryos of P. abies that has ever been reported. Callus induction from either the middle or the end of the hypocotyl of the embryos began after 2-3 weeks. Three types of calli were recovered: (a) globular, (b) light green compact, (c) white mucilaginous. Only the white mucilaginous calli were embryogenic. The globular and light green-compact calli never become embryogenic, even after several subcultures. The development of somatic embryos was accomplished on half-strength macro-elements of NSIII medium containing 1 MUM alpha-naphthaleneacetic acid, 1 MUM abscisic acid, and 3% sucrose. The addition of 10(-7) M buthionine sulfoximine to the medium increased the development of somatic embryos by three fold. These results suggest that there is a great potential for increasing the frequency and development of somatic embryos in P. abies. Careful selection of the genotype and modification of the culture medium is required. PMID- 24232268 TI - Analysis of plants regenerated from protoplast fusions between Brassica napus and Eruca sativa. AB - Protoplasts from etiolated hypocotyls of Brassica napus stained with carboxyfluorescein were fused with mesophyll protoplasts from Eruca sativa. Hybrid cells could be identified under the light microscope by (1) fully developed chloroplasts derived from E. sativa and (2) the cytoplasmic strands of the B. napus hypocotyl protoplasts, or (3) by the presence of both red and green fluorescence when investigated under UV light. The heterokaryons were selected using either a micro-manipulator or a flow sorter. On average, 5.4% of the calli obtained after selection differentiated into shoots. Regenerated shoots were subjected to isozyme analysis for verification of their hybrid character. Of the 23 hybrids successfully transferred to the greenhouse, 11 were asymmetric according to isozyme analysis. The nuclear DNA content of the hybrids was determined by flow cytometry, which gives an estimate of chromosome number. Most of the hybrids had a DNA content, and thus a chromosome number, that deviated from the expected sum of the parents. Almost all of the hybrids had some degree of fertility and produced seeds. Seed set, expressed as seeds per pollinated flower, was on average 7% of that of B. napus in the case of self-pollination and 26% of that of B. napus when backcrossed to B. napus. The chloroplast genotype was investigated in 13 hybrids. Of these, 11 had chloroplasts derived from B. napus, while only 2 had chloroplasts of E. sativa origin. PMID- 24232269 TI - Biochemical versatility of amphiploids derived from crossing Dasypyrum villosum Candargy and wheat: genetic control and phenotypical aspects. AB - The biochemical complexity and its consequence has been investigated in the amphiploids M x v and CS x v derived from crossing the tetraploid wheat Triticum turgidum var durum cv 'Modoc' and the hexaploid wheat T. aestivum cv 'Chinese Spring', respectively, with Dasypyrum villosum. Electrophoretic analysis of variation in six enzyme systems (GOT, ADH, GPI, SOD, EST, and LPX) and in high molecular weight glutenin seed storage proteins indicated that in the amphiploids these proteins were specified by a minimum of seven sets of homologous genes on wheat and D. villosum chromosomes and that in each set there were allelic differences. The enzymes detected in each amphiploid were fully accounted for by simple additivity of protomers specified by the homologous genes inherited from their parents. The amphiploids also expressed novel oligomeric enzymes not produced in either one of their parents. The ascertained expression for all the alleles inherited by both parents and the resulting biochemical complexity suggested that some peculiar feature of the amphiploids such as high nitrogen content in the plant and in the kernels and their immunity to the powdery mildew disease caused by both Erysiphe graminis f.sp. tritici and E. graminis f. sp. haynaldiae may be the consequence of the indicated complexity but specified by other sets of genes. The biochemical complexity of the M x v amphiploid may be the basis for its versatility as new crop species. PMID- 24232270 TI - A new method for hybrid seed production based on cytoplasmic male sterility combined with a lethal gene and a female sterile pollenizer in Capsicum annuum L. AB - A new improved method for hybrid seed production was successfully tested. This method is based on using a cytoplasmic male sterile line possessing a lethal gene with action that can be easily inhibited and a female sterile pollenizer. The lethal gene ensures 100% purity of the F1 crop. The female sterile pollenizer provides a permanent abundant flowering with excess of pollen grains that leads to increased hybrid seed production without additional labour expenses. The described scheme is applicable for other crops as well. PMID- 24232271 TI - Molecular analysis of organelle DNA of different subspecies of rice and the genomic stability of mtDNA in tissue cultured cells of rice. AB - Chloroplast (ct) and mitochondrial (mt) DNAs were isolated from two subspecies of rice (Oryza sativa), japonica (Calrose 76) and indica (PI353705) and compared by restriction endonuclease fragment pattern analysis. Similarly, PI353705 (A5) mtDNA was also compared with the mtDNA of its long term tissue cultured line, BL2. Variation in the ctDNA of the 2 subspecies was detected with two (AvaI and BglI) of the 11 restriction endonucleases tested, whereas their mtDNAs showed considerable variation when restricted by PstI, BamHI, HindIII and XhoI endonucleases. Thus, the chloroplast DNA was more highly conserved than the mtDNA in the subspecies comparisons. Only minor variation was observed between the restriction endonuclease patterns of the mtDNAs of BL2 and A5. Southern blots of mtDNA were hybridized with heterologous probes from maize and spinach organelle genes. Differences were found in the hybridization patterns of the two subspecies for six of the eight (mitochondrial and chloroplast) probes tested. Two of the seven (mitochondrial) probes (coxII and 26S rRNA) detected tissue culture generated variation in mtDNA. The relative values of restriction endonuclease and hybridization patterns for studying phylogenetic and genetic relationships in rice are discussed. PMID- 24232272 TI - Organ growth of selected lines of chickens and their F1 crosses to a common body weight or age. AB - Organ growth of male chickens selected for high and low 56-day body weight and their reciprocal F1 crosses was compared at a common age (56 days) or at a common body weight (180 g). Organs that differed at a common body weight included weights of proventriculus, small intestine, lungs, feathers and abdominal fat and length of esophagus. Organ weights that differed at a common age included esophagus, gizzard, heart, liver, lungs, breast, legs, feathers and abdominal fat, and lengths of shank, esophagus and small intestine. Heterosis for most organs was less than 15%. Those exhibiting heterosis greater than 30% included weights of fat depots and feathers, plus lengths of the esophagus, small intestine and shank. Heterosis for these traits, however, varied depending on whether comparisons were made at common body weight or age. These results imply that biological functions of organs at specific ages may not reflect the situations at common body weights and suggest differences in resource allocations among populations. PMID- 24232273 TI - Biparental inheritance of chloroplast DNA and the existence of heteroplasmic cells in alfalfa. AB - Mapping of chloroplast DNA (ctDNA) restriction fragment patterns from a chlorophyll deficient mutant and two phenotypically normal alfalfa genotypes (Medicago sativa L.) has demonstrated the existence of a distinct ctDNA genotype from each source. These unique restriction fragment patterns were utilized to identify maternal or paternal origin of ctDNA in hybrid plants from crosses involving the normal alfalfa genotypes as females and the yellow-green chlorophyll deficient sectors as males. Progeny from these crosses expressing the yellow-green sectored phenotypes contained paternal ctDNA in the chlorophyll deficient sectors and maternal ctDNA in the normal sectors, confirming biparental plastid inheritance. The existence of mixed cells containing both mutant and normal plastids at various stages of sorting-out was observed by transmission electron microscopy of mesophyll cells in mosaic tissue from hybrid plants. This observation verified the biparental transmission of plastids in alfalfa. PMID- 24232274 TI - Genetic basis of resistance to zonate leaf spot disease in forage sorghum. AB - Generation mean analysis was carried out for ten crosses between two resistant and two susceptible parents to find the genetic basic of resistance to zonate leaf spot disease in forage sorghum. In all crosses except one, at least one type of non-allelic interaction was present. Both additive and dominance gene effects were significant for most crosses. Duplicate type epistasis was present for the inheritance of this disease. Resistance to this disease revealed overdominance. Appropriate breeding plans were suggested to exploit the disease resistance. PMID- 24232275 TI - Production and viability of unreduced gametes in triploid interspecific blueberry hybrids. AB - Three triploid (2n=3x=36) blueberry hybrids were obtained by hand-pollinating approximately 7,000 flowers of tetraploid highbush blueberry cultivars (based on Vaccinium corymbosum L.) with pollen from the diploid species V. elliottii Chapm. Meiotic analysis of these triploids revealed trivalents, bivalents and univalents in all metaphase I cells, with lagging chromosomes evident at anaphase I. Pollen of the three triploids was mostly aborted and did not stain with acetocarmine. However, the three triploids did produce from 0.9%-1.3% giant pollen grains that stained with acetocarmine and were present as monads, dyads or triads, rather than the normal tetrads. Pollination of 10,853 flowers of hexaploid V. ashei Reade cultivars with pollen from the triploids produced 266 berries, which averaged fewer than two fully-developed seeds per berry. One triploid clone showed partial female fertility when crossed to hexaploids, self-pollinated, or intercrossed with other triploids. Ploidy levels of the resulting hybrids were determined. PMID- 24232276 TI - Half sib selection for resistance to powdery mildew (Erysiphe graminis DC. f.sp. secalis Marchal) in rye populations. AB - Three rye populations originating from different cultivars were subjected to half sib progeny selection for three cycles to improve their resistance to powdery mildew (Erysiphe graminis DC. f.sp. secalis Marchal). Selection was carried out in the greenhouse (measurement of spore production at the three-leaf stage), in the field (scoring of mildew infections at ear emergence) or at both locations. All selections resulted in significant responses, the level of which varied depending on the genetic base of mildew resistance in the populations. Greenhouse selection was most effective when the frequency of dominant genes could be increased, whereas field selection was less effective. Estimates for heritability in the narrow sense ranged from 0.42-0.94 indicating that mildew resistance can be increased effectively. Inbred lines should be selected in base populations with a high level of quantitative resistance and/or a high frequency of dominant genes. For an effective resistance strategy in hybrid breeding such dominant genes are most valuable, and can be selected in young growth stages. In 'Strain CG' the increase of dominant resistance genes by early selection resulted in a significant improvement of kernel yield. PMID- 24232277 TI - Dwarfism and male sterility in interspecific hybrids of Epilobium : 2. Expression of mitochondrial genes and structure of the mitochondrial DNA. AB - Mitochondrial DNA (mtDNA) and transcriptional patterns of mitochondrial genes have been examined in dwarf, normal, fertile and male sterile Epilobium hybrids. No alterations or rearrangements of mitochondrial DNA could be detected in the developmentally disturbed hybrids. They exhibit restriction patterns of mtDNA that correspond exactly to those of their female parents. However, the transcription of at least one mitochondrial gene is significantly altered in the male sterile hybrid E. hirsutum x montanum. In normal plants, one mRNA of 1.6 kb hybridizes to the cytochrome c oxidase subunit II gene, while in male sterile plants a transcript of this size is lacking and instead a major transcript of 2.0 kb and two smaller ones occur. The transcript pattern of the F1 ATPase alpha subunit (atpA) gene exhibits slight alterations in sterile plants also. Since these hybrids have the same cytoplasm as normal plants, an incompatibility between the nuclear and the mitochondrial genotype may be responsible for the altered mitochondrial gene expression. No alteration of the transcripts of the mitochondrial genes tested could be detected in dwarf hybrids. The coincidence of male sterility with an altered transcription pattern of mitochondrial genes suggests that the mitochondria are involved in the occurrence of this phenotype. PMID- 24232278 TI - Gynogenetic haploid plants analysis for agronomic and enzymatic markers in maize (Zea mays L.). AB - Experiments were conducted to investigate whether selection occurs during the processes involved in the production of doubled haploids. Haploid plants produced from two hybrids, each heterozygous for isozyme markers, were subjected to genetic analysis. The distributions of doubled haploid lines and pedigree lines derived from the hybrid C123 x Oh7 were compared with regard to agronomic character. The results suggest that the populations of haploid plants obtained by in vivo gynogenesis represent a random gametic array. Thus, in order to introduce haploid plants into breeding programmes in maize, maternal haploidy seems to be a very attractive method. PMID- 24232279 TI - Eyespot resistance gene Pch-1 from Aegilops ventricosa is associated with a different chromosome in wheat line H-93-70 than the resistance factor in "Roazon" wheat. AB - The hexaploid wheat line H-93-70 carries a gene (Pch-1) that has been transferred from the wild grass Aegilops ventricosa and confers a high degree of resistance to eyespot diesease, caused by the fungus Pseudocercosporella herpotrichoides. Crosses of the resistant line H-93-70 with the susceptible wheat Pane 247 and with a 7D/7Ag wheat/Agropyron substitution line were carried out and F2 kernels were obtained. The kernels were cut transversally and the halves carrying the embryos were used for the resistance test, while the distal halves were used for genetic typing. Biochemical markers were used to discriminate whether the transferred Pch-1 gene was located in chromosome 7D, as is the case for a resistance factor present in "Roazon" wheat. In the crosses involving Pane 247, resistance was not associated with the 7D locus Pln, which determines sterol ester pattern (dominant allele in H-93-70). In the crosses with the 7D/7Ag substitution line, resistance was neither associated with protein NGE-11 (7D marker), nor alternatively inherited with respect to protein C-7 (7Ag marker). It is concluded that gene Pch-1 represents a different locus and is not an allele of the resistance factor in "Roazon" wheat. PMID- 24232280 TI - Monosomic additions in beet (Beta vulgaris) carrying extra chromosomes of Beta procumbens : 1. Identification of the alien chromosomes with the help of isozyme markers. AB - Eleven isozyme systems were used to identify the extra chromosomes, originating from Beta procumbens, in progenies of 33 monosomic additions in beet (B. vulgaris). Nine groups of monosomic additions could be distinguished, representing the nine different chromosome types of B. procumbens. PMID- 24232281 TI - Structural variations in Vicia faba mitochondrial genome. AB - A comparative analysis of the presence of minicircular DNA CCCIB in 16 different lines and cultivars of fertile Vicia faba L. plants was conducted. It was found that copy number of CCCIB ranged from several copies per mitochondrial genome to probably - zero, depending on cultivar or line. Fertility of plants in these cases was not altered. We chose 10 cultivars and lines among 16 analysed. Mitochondria of five cultivars and lines contained about two CCCIB molecules per one CCCIA. The sixth cultivar contained CCCIB at copy number several times lower. In the last four cultivars CCCIB could not be identified. Copy number analysis of CCC2 in ten chosen cultivars and lines revealed that in eight cases the quantitiy of CCC2 was equal to CCCIA. However, two other cultivars contained about two times lower quantity of CCC2. Parallel to that we observed an increase in quantity of one sequence homologous to CCC2, which in the first eight cultivars and lines could be found only in minor quantities. Comparative restriction analysis revealed notable rearrangement events in mitochondrial DNAs of ten cultivars and lines being investigated. We did not find any correlations between patterns of restriction fragments and copy number of CCCIB. In some cases, rearrangements in Vicia faba mitochondrial genomes caused a duplication of sequences homologous to the Zea mays coxII gene. PMID- 24232282 TI - Brassica taxonomy based on nuclear restriction fragment length polymorphisms (RFLPs) : 2. Preliminary analysis of subspecies within B. rapa (syn. campestris) and B. oleracea. AB - Preliminary analysis using nuclear RFLPs provided evidence that subspecies within Brassica rapa originated from two different centers. One center is in Europe, represented by turnip and turnip rape from which the oilseed sarson was derived. A second center is in South China containing a variety of Chinese vegetables of which pak choi and narinosa seem to be the most ancient forms. Based on RFLP data, the accessions of B. oleracea examined could be divided into three distinct groups, represented by thousand head kale, broccoli and cabbage. Thousand head kale and Chinese kale appear to be the primitive types. Observations of parallel variation among subspecies of both species are discussed. PMID- 24232283 TI - Pollen competitive ability in maize: within population variability and response to selection. AB - Male gametophytic selection can play a special role in the evolution of higher plant populations. The main assumption - gametophytic-sporophytic gene expression of a large portion of a plant's genes - has been proven by a number of studies. Population analyses have revealed a large amount of variability for male gametophytic fitness. However, the data available do not prove that at least a portion of this variability is due to postmeiotic gene expression. This paper reports the analysis of a synthetic population of maize based on a gametophytic selection experiment, carried out according to a recurrent scheme. After two cycles of selection, the response was evaluated for gametophytic and sporophytic traits. A parameter representing pollen viability and time to germination, although showing a large amount of genetic variability, was not affected by gametophytic selection, indicating that this variability is largely sporophytically controlled. Pollen tube growth rate was significantly affected by gametophytic selection: 21.6% of the genetical variability was released by selection. Correlated response for sporophytic traits was observed for mean kernel weight: 15.67% of the variability was released. The results are a direct demonstration that pollen competitive ability due to pollen tube growth rate and kernel development are controlled, to a considerable extent, by genes expressed in both tissues. They also indicate that gametophytic selection in higher plants can produce a higher evolution rate than sporophytic selection; it can thus serve to regulate the amount of genetic variability in the populations by removing a large amount of the genetic load produced by recombination. PMID- 24232284 TI - A comparison of cytoplasmic revertants to fertility from different CMS-S maize sources. AB - The mitochondrial genome organizations of a number of independent culture-derived fertile CMS-S revertants with the nuclear genotype W182BN were compared to spontaneous field revertants with the genotypes WF9, M825/Oh07 and 38-11. Regions of the genome around sequences homologous to the terminal repeats of the linear S1 and S2 episomes characteristic of CMS-S mitochondria were used as hybridization probes on Southern blots of BamHI and SalI digested mitochondrial DNA. The results obtained suggest that the nuclear, not the cytoplasmic, genotype of the parent plant affects the type of novel mitochondrial DNA organization found in the revertant. The DNA reorganization during reversion from CMS-S in tissue culture appears to be similar to that observed in spontaneous revertants obtained during the normal plant life-cycle. Unlike the situation for reversion from CMS-T, no common DNA sequence or reading frame appeared to be lost or disrupted in revertants. PMID- 24232285 TI - Inheritance of large mitochondrial RNA's in alfalfa. AB - Several large RNA molecules that migrated to electrophoretic positions ranging from 1.7-10 kb were observed in preparation of alfalfa (Medicago sativa) mitochondria. F1 progenies inherited the RNA's from both maternal and paternal parents (Fig. 1). Treatment of intact mitochondria with RNase A failed to remove the RNA's, indicating that they were contained within an RNase impermeable compartment. Further purification of mitochondria in linear sucrose gradients failed to separate the RNA's from mitochondria. Transmission electron microscopic examination of sucrose gradient purified mitochondria revealed that mitochondria were free of contamination by virus-like particles, indicating that the RNA's were contained within the mitochondrion. Biparental inheritance of large mitochondrial RNA's in alfalfa provides evidence that mitochondria are inherited biparentally in this species. PMID- 24232286 TI - Detection of linkage between restriction fragment length polymorphism markers and quantitative traits. AB - Methodologies commonly used to detect linkage of marker loci to loci affecting quantitative traits are discussed. It is shown that variances for the quantitative trait differ among marker genotypes when using F2 or pooled backcross data if linkage exists. Hence, to analyze this type of data by single factor ANOVA or other statistical techniques that assume a common variance is inadequate. Restriction fragment length polymorphism (RFLP) markers are a powerful tool in plant breeding but cost is an important drawback; hence, a methodology is suggested to obtain the minimum number of plants in F2 populations to detect such linkage. PMID- 24232287 TI - A Drosophila model of improving the fitness of translocations for genetic control : 1. Autosomal translocations with euchromatic breakpoints. AB - Translocations with euchromatic breakpoints were generated in lethal-free autosomes of Drosophila melanogaster. Pairs of initially homozygous-lethal translocations, matched for one breakpoint, were allowed to recombine for ten generations. At the end of the experiment, 10/47=21% of crosses (representing 8/26=31% of the intial translocations) had at least one line with at least one homokaryotypic third-instar larva, detected among a small sample of salivary gland preparations from each cross. Among these ten crosses, chromosome extractions were performed; 5/10 of the crosses (probably representing 4/8 of the translocations) had at least one chromosome set with relative viability greater than 15%-25%. To a first (and conservative) approximation, 5/47=11% of crosses showed improvement of viability of 1 of the translocations in the cross during the controlled recombination regime; overall, 4 of the 26 translocations (15%) showed improvement of viability. Partly because of the conservative criterion of viability used, this figure is less than the 20% of translocations that theoretically should be improvable. Pseudohomokaryotypes (pairs of translocations with both breakpoints nearly matching) did not behave as very fit homokaryotypes. However, some of them generated viable hyperploid assortment products that might be of practical interest to mask deleterious effects at breakpoints of translocations. The improvement of fitness of at least a proportion of low fitness translocation stocks by the use of a controlled recombination procedure should be feasible for many pest species. PMID- 24232288 TI - Threonine metabolism and embryonic stem cell self-renewal. AB - PURPOSE OF REVIEW: Embryonic stem cells (ESCs) undergo unlimited self-renewal while maintaining a pluripotency, which is defined as the ability to develop into cells of all three embryonic germ layers. ESC self-renewal is characterized by special proliferative and epigenetic properties and a unique metabolic profile. One of the key features of this specialized nutritional metabolism is a stringent requirement for the amino acid threonine. Until recently, little was known about amino acid metabolism in stem cells beyond their general role in protein synthesis. Recent findings demonstrating a central role for threonine metabolism in multiple aspects of stem cell biology will be presented in this review. RECENT FINDINGS: Amino acid catabolism supplies essential building blocks for biosynthetic pathways and for chemical modification of chromatin. In a series of recent studies employing combinative approaches of metabolomics, nutrition and genetics, the amino acid threonine was identified as an essential nutrient for mouse ESC (mESC). An unexpected finding from these studies was that in addition to its well known importance as protein precursor, threonine dehydrogenase mediated threonine catabolism provides essential metabolic building blocks for use in multiple biosynthetic pathways and epigenetic modifications required for self-renewal and maintenance of pluripotency. SUMMARY: Recent studies on threonine catabolism in mESCs suggest that amino acids can play both powerful biosynthetic and signaling roles in stem cells. These results described in mESCs should stimulate a new research area on the effect of amino acid metabolism in stem cell self-renewal and differentiation. PMID- 24232289 TI - ? PMID- 24232291 TI - A case of bismuth intoxication with irreversible renal damage. AB - Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Intoxications with CBS are rare. In a few case reports, acute renal failure was described, but the literature review revealed no chronic renal failure related to CBS intoxication. In this case report we present a 21-year old female with chronic renal failure after a one year follow-up of CBS intoxication. PMID- 24232290 TI - Mobile, cloud, and big data computing: contributions, challenges, and new directions in telecardiology. AB - Many studies have indicated that computing technology can enable off-site cardiologists to read patients' electrocardiograph (ECG), echocardiography (ECHO), and relevant images via smart phones during pre-hospital, in-hospital, and post-hospital teleconsultation, which not only identifies emergency cases in need of immediate treatment, but also prevents the unnecessary re hospitalizations. Meanwhile, several studies have combined cloud computing and mobile computing to facilitate better storage, delivery, retrieval, and management of medical files for telecardiology. In the future, the aggregated ECG and images from hospitals worldwide will become big data, which should be used to develop an e-consultation program helping on-site practitioners deliver appropriate treatment. With information technology, real-time tele-consultation and tele-diagnosis of ECG and images can be practiced via an e-platform for clinical, research, and educational purposes. While being devoted to promote the application of information technology onto telecardiology, we need to resolve several issues: (1) data confidentiality in the cloud, (2) data interoperability among hospitals, and (3) network latency and accessibility. If these challenges are overcome, tele-consultation will be ubiquitous, easy to perform, inexpensive, and beneficial. Most importantly, these services will increase global collaboration and advance clinical practice, education, and scientific research in cardiology. PMID- 24232292 TI - Scaled-up production of plasmonic nanoparticles using microfluidics: from metal precursors to functionalized and sterilized nanoparticles. AB - An exquisite control of synthesis parameters is generally required in nanomaterial synthesis to guarantee consistency in the essential characteristics such as size and shape. On the other hand, reliable scaled-up production of nanomaterials is required in order to achieve the production rates required for emerging nanotechnology applications while delivering a consistent product with the intended characteristics, avoiding the traditional batch-to-batch deviations. The continuous production of nanomaterials is challenging because of the difficulties involved in translating the complexity of nanomaterial synthesis into on-line operations. In this regard, microfluidic platforms stand out over conventional batch reactors due to their superior performance, easy scalability and reliability. Here, a continuous, scaled-up synthesis of high quality plasmonic hollow gold nanoparticles is reported for the first time. Not only was the throughput significantly higher than in a batch reactor, but also the microfluidic system allowed the on-line implementation of two new stages in nanomaterial production: surface functionalization and sterilization. PMID- 24232294 TI - Photolithotrophy, photoheterotrophy, and chemoheterotrophy: Patterns of resource utilization on an annual and a diurnal basis within a pelagic microbial community. AB - An annual investigation of rates of photolithotrophy, photoheterotrophy, and chemoheterotrophy utilizing glucose and bicarbonate was made within the pelagic zone of a small, hardwater, southwestern Michigan lake. Sampling proceeded on a monthly, diurnal, and depth-wise basis. Annual mean photoheterotrophic uptake was estimated at 2.6MUg C m(-3)h(-1). Two periods of relatively high activity were observed: one during spring overturn and the second during the late summer period. In general, greatest contributions to overall carbon cycling occurred during morning to midday incubation periods and at intermediate depths within the water column. Rates of chemoheterotrophy averaged 6.9MUg C m(-3)h(-1) and were relatively uniform throughout the annual period. Greatest overall chemoheterotrophic activity was associated with periods of overturn. In general, this activity increased throughout the day and with increasing depth within the water column. The annual mean for photolithotrophic fixation was 1.33 mg C m( 3)h(-1). Greatest contributions to rates of photosynthesis were associated with epilimnetic waters during early morning and midday incubations. Relatively minor contributions to inorganic fixation were made by waters below the 6-meter contour. Spring overturn and late summer represented periods of particularly great photolithotrophic activity. Quantitative comparisons among carbon pathways indicate that rates of pelagic heterotrophy, both photo- and chemoheterotrophy combined, contribute small quantities of carbon to overall carbon metabolism in this oligotrophic system. Qualitative comparisons among pathways indicate strong spatial and temporal separation. The late summer period showed greatest seasonal separation of the three pathways. Spring values represented a period of relatively high activity for all three pathways. On a depth-wise basis, photolithotrophic activity was greatest near the surface and chemolithotrophic activity greatest near the bottom. Photoheterotrophy took an intermediate position between the two. Diurnally, photoheterotrophy and photolithotrophy showed greatest activity during midday and early morning periods, whereas chemoheterotrophy increased throughout the daylight period and reached maximal values in sunset incubations. PMID- 24232293 TI - Defining the critical-sized defect in a rat segmental mandibulectomy model. AB - IMPORTANCE: Advances in tissue engineering offer potential alternatives to current mandibular reconstructive techniques; however, before clinical translation of this technology, a relevant animal model must be used to validate possible interventions. OBJECTIVE: To establish the critical-sized segmental mandibular defect that does not heal spontaneously in the rat mandible. DESIGN AND SETTING: Prospective study of mandibular defect healing in 29 Sprague-Dawley rats in an animal laboratory. INTERVENTIONS: The rats underwent creation of 1 of 4 segmental mandibular defects measuring 0, 1, 3, and 5 mm. All mandibular wounds were internally fixated with 1-mm microplates and screws and allowed to heal for 12 weeks, after which the animals were killed humanely. MAIN OUTCOMES AND MEASURES: Analysis with micro-computed tomography of bony union and formation graded on semiquantitative scales. RESULTS: Seven animals were included in each experimental group. No 5-mm segmental defects successfully developed bony union, whereas all 0- and 1-mm defects had continuous bony growth across the original defect on micro-computed tomography. Three of the 3-mm defects had bony continuity, and 3 had no healing of the bony wound. Bone union scores were significantly lower for the 5-mm defects compared with the 0-, 1-, and 3-mm defects (P < .01). CONCLUSIONS AND RELEVANCE: The rat segmental mandible model cannot heal a 5-mm segmental mandibular defect. Successful healing of 0-, 1-, and 3-mm defects confirms adequate stabilization of bony wounds with internal fixation with 1-mm microplates. The rat segmental mandibular critical-sized defect provides a clinically relevant testing ground for translatable mandibular tissue engineering efforts. PMID- 24232295 TI - Effects of sudden temperature shifts on pure cultures of four strains of freshwater bacteria. AB - Three psychrotrophic and one mesophilic strains were isolated from winter water samples of different freshwater biotopes and identified asCytophaga johnsonae (C 21),Cytophaga sp. (M-17),Pseudomonas fluorescens (KD), andEnterobacter cloacae (BS-2). Temperature shift-up experiments with emphasis on low temperatures were carried out with aerated pure batch cultures in glucose mineral medium. The effects of sudden temperature increases on growth rates and substrate conversion were investigated. All three psychrotrophic strains in the temperature increase experiments at low temperatures showed differing reactions within the linear zone of the Arrhenius plot. TheC. johnsonae (C-21) shift-up cultures adjusted the growth rate immediately to the rate of the temperature adapted cultures, whereasCytophaga sp. (M-17) shift-up cultures showed a lower andP. fluorescens (KD) a higher growth rate. The mesophilicE. cloacae (BS-2), likeC. johnsonae (C 21), adjusted immediately to the new growth rate. Substrate conversion increased in all experiments immediately after the shift-up. The extracellular substrate conversion byP. fluorescens (KD) of glucose to gluconate and 2-ketogluconate was particularly affected by the sudden temperature increase. PMID- 24232296 TI - Coliforms and enterococci isolated from the intestinal tract of conventional mice. AB - Coliforms and enterococci were isolated from the intestinal tract of infant (12 day-old) and adult (6-to 8-week-old) conventional mice. Eighty coliform isolates and eighty enterococcal strains were grouped according to their ability to ferment or hydrolyze various substrates. Sixty-one of the coliform isolates were identified asEscherichia coli. The remaining 19 strains were similar toE. coli, but did not producebeta-galactosidase. The enterococci belonged to two species:Streptococcus faecium andS. faecalis. Four biotypes ofS. faecium and two biotypes ofS. faecalis were detected. Xylosefermenting enterococci were isolated with a higher frequency from infant mice than from adults. PMID- 24232297 TI - Association of rat, pig, and fowl biotypes of lactobacilli with the stomach of gnotobiotic mice. AB - We grouped 20 isolates of lactobacilli from the stomach of conventional rats, 21 isolates from pig stomachs, and 19 isolates from the crop of fowls according to their ability to ferment N-acetylglucosamine, dextrin, cellobiose, gum arabic, and xylan. Most of the isolates did not resemble previously describedLactobacillus species. Representative group A isolates were associated with germ-free mice. Only a rat isolate was able to colonize the keratinized squamous epithelium of the stomach of gnotobiotic mice. PMID- 24232298 TI - Relevance of the ecology ofCitrus yeasts to the diet ofDrosophila. AB - A study of the yeast flora of necrotic oranges and associatedDrosophila yielded a total of 221 isolates composed ofKloeckera apiculata (75),Pichia fermentans (75),Pichia kluyveri (50),Torulopsis stellata (17),Hanseniaspora uvarum (2),P. membranaefaciens (1), andCandida vini (1). The yeast species of all samples of oranges and adultDrosophila were very similar; however, the speciesof Drosophila contained a higher proportion ofP. fermentans and a lower proportion ofK. apiculata than was found in the rotting oranges.P. fermentans was subsequently found more frequently on the surface of the necrotic tissue, where the flies feed, than was found internally. SinceP. fermentans characteristically produces a pellicle and pseudomycelium andK. apiculata does not, it is concluded that the growth characteristics of the yeasts are an important factor determining adultDrosophila diets. PMID- 24232299 TI - Effect of temperature on violacein production in a psychrotrophicChromobacterium from Lake Ontario sediment. AB - A truly psychrotrophic strain ofChromobacterium, which was isolated from Lake Ontario sediment and characterized asChromobacterium lividum, was found to be capable of pigment production that was completely prevented at 0 degrees C, although growth readily occurred. Normal pigment formation occurred at 15 degrees C, 20 degrees C, and 25 degrees C. The prevention of synthesis of the pigment at 0 degrees C, which was confirmed spectrophotometrically to be violacein, was not reversed by the presence of various carbon sources, although all except one acted as growth substrates. In addition, some of the carbon sources actually inhibited pigment production at 20 degrees C, preventing violacein synthesis in the presence of pyruvate which was shown to allow pigmentation. Similar results were obtained under both liquid and solid media cultivation conditions. PMID- 24232300 TI - Microscopic examination of bacteria in Fe(III)-oxide deposited from ground water. AB - Ochreous sludge deposited in the course of aeration of ground water contained an assortment of bacterial forms and structures which were investigated by light microscopy, scanning electron microscopy, and transmission electron microscopy. Bacterial structures were often covered by iron deposition which could be removed by acidification of the samples. Sulfuric acid treatment was consistently better than hydrochloric acid to dissolve iron without a considerable damage to the bacterial cells. Partial dissolution of amorphous ferric iron was achieved by acidifying the samples with oxalic acid or citric acid prior to the preparation for electron microscopy. PMID- 24232301 TI - Relative influence of temperature and electron donor and electron acceptor concentrations on bacterial sulfate reduction in saltmarsh sediment. AB - The relative importance of three environmental variables known to influence the rate of bacterial sulfate reduction was examined using sediment from a saltmarsh pan. The variables investigated were temperature, electron donor concentration, and electron acceptor concentration. Their relative influence on the rate of bacterial sulfate reduction was examined with multiple replicate sediment samples in which the variables were experimentally adjusted. Sulfate reduction rates were measured with(35)SO 4 (2-) .The relative importance of each variable to sulfate reduction rate was assessed with multiple regression analysis by calculating the standardized partial regression coefficients, and the results were compared with the ranges of the three variables encountered in the natural sediment. Temperature proved to have the greatest influence, followed by electron donor and electron acceptor concentrations, in that order. The sulfate concentration was shown to have little influence on sulfate reduction rate at seawater concentrations of sulfate, but its effect increased if sulfate concentrations were diminished compared to those of seawater. PMID- 24232302 TI - Seasonal temperature as a factor influencing bacterial sulfate reduction in a saltmarsh sediment. AB - The population of sulfate-reducing bacteria in saltmarsh sediment was examined at monthly intervals by plate-counting and by determining the response of sulfate reduction rates to environmental temperature using(35)SO 4 (2-) . The sulfate reduction rate was shown to be related to temperature by an Arrhenius function.The temperature characteristic of the population of sulfate-reducing bacteria did not vary significantly with season, and was shown to be equivalent to 20.4 kcals mole(-1), a Q10 of 3.5. Apart from one anomolous result, the monthly value for the Arrhenius constant also did not show any significant variation throughout the year. There was no seasonal trend of optimum temperature for sulfate reduction.The results suggested that, although environmental temperature was the dominant variable influencing sulfate reduction rates in the sediment, there was no detectable response or adaptation of the sulfate-reducing population to seasonally changing environmental temperature. PMID- 24232304 TI - Social correlates of clotting disorders in adults and the very old: UK Understanding Society cohort, 2009-2010. PMID- 24232303 TI - Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo. AB - Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5 FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5 FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. PMID- 24232305 TI - Sustained remission and reversal of end-organ dysfunction in a patient with anaplastic myeloma. PMID- 24232306 TI - Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature. AB - This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies. PMID- 24232307 TI - New perspectives of iron deficiency as a risk factor for ischemic stroke. PMID- 24232308 TI - Large granular lymphocytic leukemia of gamma-delta T cells: cytogenetics and fluorescence in situ hybridization study. PMID- 24232309 TI - Intraoperative assessment of spinal vascular flow in the surgery of spinal intramedullary tumors using indocyanine green videoangiography. AB - BACKGROUND: The authors demonstrate the utility of indocyanine green videoangiography (ICG-VA) for intraoperative vascular flow assessment in the surgery of a variety of spinal intramedullary tumors to achieve an additional level of safety as well as precision with the surgical procedure. METHODS: Fourteen patients with spinal intramedullary tumors (nine cervical and five thoracic) operated on between August 2011 and April 2013 were included in the present study. A fluorescence surgical microscope was used to perform ICG-VA after standard exposure of the lesion to assess the dynamic flow of the spinal microvasculature. RESULTS: Twenty-seven ICG-VA injections were performed in 14 cases. Pathological diagnosis of the tumors included ependymoa, astrocytoma, cavernous malformation, or hemagioblastoma. There were no complications or side effects related to ICG-VA. Intraoperative ICG-VA provided dynamic flow images of the spinal microvasculature in accordance with the progress of surgical procedures. Angiographic images could be divided into arterial, capillary, and venous phases. All angiographic images were well integrated into the microscopic view. The utility of ICG-VA could be summarized into three categories: (1) Localization of normal spinal arteries and veins, (2) assessment of posterior spinal venous circulation, and (3) differentiation of feeding arteries, tumor, and draining veins. CONCLUSIONS: Intraoperative vascular flow assessment using ICG-VA was easy, repeatable, and practical without any significant procedure related risks. ICG-VA can be used for careful analysis of spinal microvascular flow or anatomical orientation, which is necessary to ensure safe and precise resection of spinal intramedullary tumors. PMID- 24232310 TI - Oral health conditions affect functional and social activities of terminally ill cancer patients. AB - PURPOSE: Oral conditions are established complications in terminally ill cancer patients. Yet despite significant morbidity,the characteristics and impact of oral conditions in these patients are poorly documented. The study objective was to characterize oral conditions in terminally ill cancer patients to determine the presence, severity, and the functional and social impact of these oral conditions. METHODS: This was an observational clinical study including terminally ill cancer patients (2.5-3-week life expectancy). Data were obtained via the Oral Problems Scale (OPS) that measures the presence of subjective xerostomia, orofacial pain, taste change, and the functional/social impact of oral conditions and a demographic questionnaire. A standardized oral examination was used to assess objective salivary hypofunction, fungal infection, mucosal erythema, and ulceration. Regression analysis and t test investigated the associations between measures. RESULTS: Of 104 participants, most were >=50 years of age,female, and high-school educated; 45 % were African American, 43 % Caucasian, and 37 % married. Oral conditions frequencies were: salivary hypofunction (98 %), mucosal erythema (50 %), ulceration (20 %), fungal infection(36 %), and other oral problems (46 %). Xerostomia, taste change, and orofacial pain all had significant functional impact; p <.001, p =.042 and p <.001, respectively. Orofacial pain also had a significant social impact (p <.001). Patients with oral ulcerations had significantly more orofacial pain with a social impact than patients without ulcers (p =.003). Erythema was significantly associated with fungal infection and with mucosal ulceration (p <.001). CONCLUSIONS: Oral conditions significantly affect functional and social activities in terminally ill cancer patients. Identification and management of oral conditions in these patients should therefore be an important clinical consideration. PMID- 24232311 TI - Secondary glaucoma due to chronic scleritis: trabeculectomy in scleromalacia: a case report. PMID- 24232312 TI - Macular dystrophy presenting in one of two siblings with limb-girdle muscular dystrophy type 2L due to mutation of ANO5. PMID- 24232313 TI - Long-term outcomes and risk factors for failure with the EX-press glaucoma drainage device. AB - PURPOSE: To report on the long-term outcomes and risk factors for failure with the EX-PRESS shunt implanted under a scleral flap. SETTINGS: Eye Department, University of Ancona, Ancona, Italy and the Oxford Eye Center, University of Witwatersrand, Johannesburg, South Africa. METHODS: The medical records of glaucoma patients who underwent consecutive EX-PRESS implantations under a scleral flap between 2000 and 2009 were reviewed. The operations were performed by two experienced surgeons using an identical surgical technique. The potential risk factors for failure that were analysed included age, sex, race, glaucoma type, previous antiglaucoma medications, previous glaucoma surgeries, diabetes, and smoking. Complete success was defined as postoperative intraocular pressure (IOP) 5 mm Hg>IOP<18 mm Hg without antiglaucoma medications. Qualified success was defined as 5 mm Hg>IOP<18 mm Hg with or without antiglaucoma medications. RESULTS: Two hundred and forty-eight eyes of 211 consecutive patients were included. The mean IOP was reduced from 27.63 +/- 8.26 mm Hg preoperatively (n=248) to 13.95 +/- 2.70 mm Hg at 5 years (n=95). The mean follow-up was 3.46 +/ 1.76 years. Complete and qualified success rates decreased gradually from 83% and 85% at 1 year to 57% and 63% at 5 years follow-up, respectively. The risk factors for failure were diabetes, non-Caucasian race, and previous glaucoma surgery. Complete success rates of diabetic patients and non-Caucasian patients decreased from 63% and 75% at 1 year to 42% and 40% at 5 years follow-up, respectively. CONCLUSIONS: EX-PRESS success rates decrease over time but compare favourably with trabeculectomy literature data. The main identifiable risk factors for failure are diabetes, non-Caucasian race, and previous glaucoma surgery. PMID- 24232314 TI - Spontaneously resolved exudative retinal detachment caused by orbital cellulitis in an immunocompromised adult. PMID- 24232315 TI - Flap characteristics, predictability, and safety of the Ziemer FEMTO LDV femtosecond laser with the disposable suction ring for LASIK. AB - AIMS: The outcomes of laser-assisted in situ keratomileusis (LASIK) operations performed with the Classic FEMTO LDV femtosecond laser using the plastic single use suction ring (Ziemer Ophthalmic Systems) and the Allegretto Wave Concerto 500 Hz excimer laser (Wavelight AG) are presented in terms of accuracy, predictability, and safety of the operation. METHODS: A FEMTO LDV plastic suction ring was used for flap creation in 342 eyes of 179 patients. The intended flap thickness was 90 MUm. The size of the suction ring varied from 9.0 to 10.0 mm. Flap dimensions were measured and correlated to preoperative characteristics. RESULTS: Mean flap thickness was very constant, 89.6 +/- 2.0 MUm (range 84-97). In 163 bilateral operations, the second flap was 1.1 MUm thinner than the one cut first (P<0.0001). Mean flap diameter was 9.4 +/- 0.2 mm (range 8.1-9.9). Mean hinge length was 3.9 +/- 0.2 mm (range 3.0-4.2). In hyperopic eyes, flap thickness correlated negatively with keratometric power K1 and flap diameter. In hyperopic eyes, flap diameter correlated positively with spherical equivalent refraction and with keratometric power K1 as well as hinge length both in myopic and hyperopic eyes. Complications were reported in 12 (3.5%) eyes. Complications were very mild and none of them prevented further refractive laser treatment. Two Snellen lines of corrected distance visual acuity were lost in one (0.3%) eye. CONCLUSION: The FEMTO LDV plastic single-use suction rings yielded accurate and reproducible flaps and were safe for the creation of thin corneal flaps. PMID- 24232317 TI - Control of the developmental pathway of tobacco pollen in vitro. AB - We developed a new method for culture of isolated pollen. Using highly homogeneous populations of immature pollen grains of Nicotiana tabacum L. prepared by means of Percoll density gradient centrifugation, we could direct their developmental pathway by regulating certain culture conditions. When the pollen population was cultured in basal medium with glutamine, most pollen grains underwent normal maturation. On the other hand, when first cultured in basal medium without glutamine, most pollen grains did not mature but after transfer to medium with glutamine and sucrose began to divide. This method for inducing pollen cell division was possible only with midbinucleate pollen grains which are characterized by having no central vacuole and no or only a few starch grains. Evidently, some essential changes necessary for the embryogenic response can be induced by glutamine starvation only in pollen grains at a specific stage. PMID- 24232316 TI - Changes in lamina cribrosa and prelaminar tissue after deep sclerectomy. AB - AIM: To determine the response of the lamina cribrosa (LC) and prelaminar tissue to a reduction of intraocular pressure (IOP) after nonpenetrating deep sclerectomy (NPDS) using enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD-OCT). METHODS: A total of 28 eyes from 28 patients presenting with primary open angle glaucoma who underwent NPDS were studied. SD OCT scans using EDI technology were obtained before surgery and 1 week, 1 month, and 3 months postoperatively. The OCT device was set to image a 15 * 10 degrees vertical rectangle centred on the optic disc. The scan closest to the optic nerve head (ONH) centre was selected for analysis. The vertical distances from three equidistant points on the reference line (Bruch's membrane opening) to the anterior prelaminar tissue surface and the anterior and posterior surfaces of the LC were measured. RESULTS: The IOP decreased from 18.7 +/- 4.3 to 9.1 +/- 4.0 at the first week, 11.4 +/- 3.7 at 1 month, and 13.1 +/- 3.6 mm Hg at 3 months postoperatively (P<0.001). There was a significant reduction of the ONH cupping at 1 week (22.3%, P<0.001), 1 month (13.7%, P<0.001), and 3 months (9.8%, P=0.001) after surgery. Anterior displacement of the LC was slight but statistically significant at 1 week (4.5%, P=0.003), 1 month (3.8%, P=0.014), and 3 months postoperatively (3.3%, P=0.010). IOP reduction was significantly correlated with a reduction of ONH cupping and anterior displacement of LC at the first week and first month (P<0.05). CONCLUSIONS: Cupping reversal after NPDS is mainly due to changes in prelaminar tissue thickness, whereas the LC changes in position are less pronounced. PMID- 24232318 TI - Localization of wheat-germ agglutinin in developing wheat embryos and those cultured in abscisic acid. AB - The time course of appearance of wheat-germ agglutinin (WGA) in the various embryonic tissues during embryogenesis in Triticum aestivum L. was studied by sensitive immunofluorescence and peroxidase-antiperoxidase detection systems. The radicle, root cap and coleorhiza first accumulated WGA in early Stage II (8-10 d post-anthesis) prior to the main period of embryo growth, while WGA was found in the epiblast and coleoptile in early and late State III, respectively. Stage III is characterized by maximum embryo growth, followed by desiccation which occurs in Stage IV. When Stage-II embryos were precociously germinated in the absence of abscisic acid (ABA) no WGA was detected in the coleoptile and epiblast of the young seedlings. In the presence of ABA, Stage-II embryos did not germinate but WGA precociously accumulated in the coleoptile and epiblast. The levels and distribution of WGA in the resulting embryo resembled those in a fully mature, dry embryo (Stage V). Barley possesses a seed lectin similar to WGA, but it is never detected in coleoptiles. Some but not all of the barley cultivars tested were found to accumulate lectin in this organ of mature embryos when treated with ABA. Thus, ABA appears to be involved in the highly regulated temporal and spatial expression of WGA during embryogenesis in cereals. PMID- 24232319 TI - Arabinogalactan proteins during the development of soybean root nodules. AB - In soybean (Glycine max (L.) Merr.) root nodules the level of hydroxyproline containing molecules is developmentally regulated. Hydroxyproline accumulates in both nodule cortex and medulla. In the cortex, the hydroxyproline is mainly localized in the cell wall, presumably as extensin, but in the medulla it is mainly in the soluble fraction as an arabinogalactan protein (AGP). Nodule specific AGPs are present at early nodulation. The highest concentration of AGP is in the nodule medulla, followed by nodule cortex, uninfected roots, leaves, flowers, pods and seeds. Root nodules and all organs of the soybean plant that were tested were found to express a tissue-specific set of arabinogalactan proteins. PMID- 24232320 TI - Involvement of the Golgi apparatus in the secretion of alpha-amylase from gibberellin-treated barley aleurone cells. AB - Localisation of alpha-amylase (EC 3.2.1.1) in barley aleurone cells treated with gibberellic acid has been achieved using protein A-gold-labelled polyclonal antibodies. Gold particles were located almost exclusively over the lumen of the rough endoplasmic reticulum and cisternae of the Golgi apparatus. The label was most concentrated over the Golgi apparatus. This indicates that the Golgi is involved in the secretion of alpha-amylase protein from aleurone cells. PMID- 24232321 TI - Prolamellar-body structure, composition of molecular species and amount of galactolipids in etiolated, greening and reetiolated primary leaves of oat, wheat and rye. AB - The greening and reetiolation process of etiolated leaves of oat, wheat and rye, possessing different types of prolamellar bodies (PLBs), was observed by electron microscopy. Oat is known to possess unusual crystalline PLBs (so-called 'narrow type'). Rye and what, which normally show PLBs with more loosely packed tubules ('wide type') during etiolation, exhibited PLBs of the narrow type after illumination and subsequent reincubation in the dark (=reetiolation). Thus the reetiolated PLBs of wheat and rye did not differ from etiolated or reetiolated oat PLBs. In parallel with the microscopic analysis, intact leaves of all developmental stages were analysed for their galactolipid content and composition of molecular species using a newly developed high-performance liquid chromatography procedure. When oat, wheat and rye were compared, differences in the molecular species and the molar ratio of the two galactolipids monogalactosyldiacylglyceride (MGDG) and digalactosyldiacylglyceride (DGDG) were found. However, no parameter showed a correlation with PLB construction, disintegration or reconstruction. The results presented in this paper are not consistent with the hypothesis that the molar ratio of MGDG/DGDG is responsible for the tubular structure of prolamellar bodies in etioplasts. PMID- 24232322 TI - Distribution of calmodulin in pea seedlings: Immunocytochemical localization in plumules and root apices. AB - Immunofluorescence techniques have been used to study the distribution of calmodulin in several tissues in young etiolated pea (Pisum sativum L.) seedlings. A fairly uniform staining was seen in the nucleoplasm and background cytoplasm of most cell types. Cell walls and nucleoli were not stained. In addition, patterned staining reactions were seen in many cells. In cells of the plumule, punctate staining of the cytoplasm was common, and in part this stain appeared to be associated with the plastids. A very distinctive staining of amyloplasts was seen in the columella of the root cap. Staining associated with cytoskeletal elements could be shown in division stages. By metaphase, staining of the spindle region was quite evident. In epidermal cells of the stem and along the underside of the leaf there was an intense staining of the vacuolar contents. Guard cells lacked this vacuolar stain. Vacuolar staining was sometimes seen in cells of the stele, but the most distinctive pattern in the stele was associated with young conducting cells of the xylem. These staining patterns are consistent with the idea that the interactions of plastids and the cytoskeletal system may be one of the Ca(2+)-mediated steps in the response of plants to environmental stimuli. Nuclear functions may also be controlled, at least in part, by Ca(2+). PMID- 24232323 TI - Immunoelectron-microscopy localization of abscisic acid with colloidal gold on Lowicryl-embedded tissues of Chnopodium polyspermum L. AB - Further study on the localization of abscisic acid (ABA) has been undertaken at the ultrastructural level in Chenopodium polyspermum L. Axillary-bud-bearing nodes on the main axis were fixed with soluble 1-(3-dimethylaminopropyl)-3 ethyl carbodiimide, then postfixed with paraformaldehyde and embedded in Lowicryl K4M at-20 degrees C. Ultrathin sections mounted on grids were successively incubated with rabbit anti-ABA antibodies and with gold-labelled goat anti-rabbit anti bodies (40 nm particle size). Control sections treated with preimmune rabbit serum and ABA-preabsorbed antibodies were devoid of label. The background staining was very low with this technique. Quantitative analysis of the immunolabelling showed that two main sites of ABA accumulation could be defined: first, plastids in cortical cells and vascular parenchyma cells associated with sieve elements and xylem vessels; second, the cell cytoplasm and nucleus in the axillary bud tip and in procambial strands. In vascular bundles, the cambial cells showed no immunoreactivity. These observations support the hypothesis for the cytoplasmic synthesis of ABA which is subsequently trapped in plastids as cells mature. PMID- 24232324 TI - Expression of nuclear genes as affected by treatments acting on the plastids. AB - In a preceding paper (Oelmuller and Mohr 1986, Planta 167, 106-113) it was shown that in the cotyledons of the mustard (Sinapis alba L.) seedling the integrity of the plastid is a necessary prerequisite for phytochrome-controlled appearance of translatable mRNA for the nuclear-encoded small subunit (SSU) of ribulose-1,5 bisphosphate carboxylase and the light-harvesting chlorophyll a/b-binding protein of photosystem II (LHCP). It was concluded that a signal from the plastid is essential for the expression of nuclear genes involved in plastidogenesis. The present study was undertaken to characterize this postulated signal. Chloramphenicol, an inhibitor of intraplastidic protein synthesis and Norflurazon, an inhibitor of carotenoid synthesis (to bring about photooxidative sensitivity of the plastids) were applied. We obtained the following major results. (i) After a brief period of photooxidative damage a rapid decrease of the above translatable mRNAs was observed. CONCLUSION: the signal is short-lived and thus required continually. (ii) Once the plastids became damaged by photooxidation, no recovery with regard to nuclear gene expression was observed after a transfer to non-damaging light conditions. CONCLUSION: even a brief period of damage suffices to prevent production of the signal. (iii) Chloramphenicol inhibited nuclear gene expression (SSU, LHCP) and plastidic development when applied during the early stages of plastidogenesis. Once a certain stage had been reached (between 36-48 h after sowing at 25 degrees C) nuclear gene expression became remarkably insensitive toward inhibition of intraplastidic translation. CONCLUSION: a certain developmental stage of the plastid must be reached before the signal is released by the plastid. (iv) Under the growth conditions we adopted in our experiments the plastids in the mesophyll cells of mustard cotyledons developed essentially between 36 and 120 (-144) h after sowing. Only during this period could translatable mRNAs for SSU and LHCP be detected. CONCLUSION: the signal is released by the plastids only during this time span. PMID- 24232325 TI - Co-function of C3-and C 4-photosynthetic pathways in C3, C 4 and C 3-C 4 intermediate Flaveria species. AB - The potential for C4 photosynthesis was investigated in five C3-C4 intermediate species, one C3 species, and one C4 species in the genus Flaveria, using (14)CO2 pulse-(12)CO2 chase techniques and quantum-yield measurements. All five intermediate species were capable of incorporating (14)CO2 into the C4 acids malate and aspartate, following an 8-s pulse. The proportion of (14)C label in these C4 products ranged from 50-55% to 20-26% in the C3-C4 intermediates F. floridana Johnston and F. linearis Lag. respectively. All of the intermediate species incorporated as much, or more, (14)CO2 into aspartate as into malate. Generally, about 5-15% of the initial label in these species appeared as other organic acids. There was variation in the capacity for C4 photosynthesis among the intermediate species based on the apparent rate of conversion of (14)C label from the C4 cycle to the C3 cycle. In intermediate species such as F. pubescens Rydb., F. ramosissima Klatt., and F. floridana we observed a substantial decrease in label of C4-cycle products and an increase in percentage label in C3-cycle products during chase periods with (12)CO2, although the rate of change was slower than in the C4 species, F. palmeri. In these C3-C4 intermediates both sucrose and fumarate were predominant products after a 20-min chase period. In the C3-C4 intermediates, F. anomala Robinson and f. linearis we observed no significant decrease in the label of C4-cycle products during a 3-min chase period and a slow turnover during a 20-min chase, indicating a lower level of functional integration between the C4 and C3 cycles in these species, relative to the other intermediates. Although F. cronquistii Powell was previously identified as a C3 species, 7-18% of the initial label was in malate+aspartate. However, only 40-50% of this label was in the C-4 position, indicating C4-acid formation as secondary products of photosynthesis in F. cronquistii. In 21% O2, the absorbed quantum yields for CO2 uptake (in mol CO2.[mol quanta](-1)) averaged 0.053 in F. cronquistii (C3), 0.051 in F. trinervia (Spreng.) Mohr (C4), 0.052 in F. ramosissima (C3-C4), 0.051 in F. anomala (C3-C4), 0.050 in F. linearis (C3 C4), 0.046 in F. floridana (C3-C4), and 0.044 in F. pubescens (C3-C4). In 2% O2 an enhancement of the quantum yield was observed in all of the C3-C4 intermediate species, ranging from 21% in F. ramosissima to 43% in F. pubescens. In all intermediates the quantum yields in 2% O2 were intermediate in value to the C3 and C4 species, indicating a co-function of the C3 and C4 cycles in CO2 assimilation. The low quantum-yield values for F. pubescens and F. floridana in 21% O2 presumably reflect an ineffcient transfer of carbon from the C4 to the C3 cycle. The response of the quantum yield to four increasing O2 concentrations (2 35%) showed lower levels of O2 inhibition in the C3-C4 intermediate F. ramosissima, relative to the C3 species. This indicates that the co-function of the C3 and C4 cycles in this intermediate species leads to an increased CO2 concentration at the site of ribulose-1,5-bisphosphate carboxylase/oxygenase and a concomitant decrease in the competitive inhibition by O2. PMID- 24232326 TI - Monoclonal antibodies directed against protoplasts of soybean cells : Generation of hybridomas and characterization of a monoclonal antibody reactive with the cell surface. AB - Splenocytes, derived from mice that had been immunized with protoplasts prepared from suspension cultures of root cells of Glycine max (L.) Merr. (SB-1 cell line), were fused with a murine myeloma cell line. The resulting hybridoma cultures were screened for the production of antibodies directed against the soybean protoplasts and were then cloned. One monoclonal antibody, designated MVS 1, was found to bind to the outer surface of the plasma membrane on the basis of several criteria: (a) agglutination of the protoplasts; (b) binding of fluorescence-labeled immunoglobulin on protoplasts yielding a ring staining pattern with prominent intensity at the edges; and (c) saturable binding by protoplasts of (125)I-labeled Antibody MVS-1. The antigenic target of Antibody MVS-1, identified by immunoblotting techniques, contained a polypeptide of relative molecular mass (Mr) approx. 400000 under both reducing and non-reducing conditions. When the antigenic target of Antibody MVS-1 was chromatographed in potassium phosphate buffer, the position of elution corresponded to that of a high-molecular-weight species (Mr 400000). These results provide the protein characterization required for the analysis of the mobility of Antibody MVS-1 bound to the plasma membrane of SB-1 cells. PMID- 24232327 TI - Immunoprecipitation of phytochrome from green Avena by rabbit antisera to phytochrome from etiolated Avena. AB - Thirty-nine antiserum preparations from eight rabbits were screened for their ability to precipitate the immunochemically distinct phytochrome that is obtained from green oat (Avena sativa L.) shoots. The antisera were obtained from rabbits immunized with either proteolytically degraded, but still photoreversible, 60-kDa (kilodalton) phytochrome, or approx. 120-kDa phytochrome, both of which were purified from etiolated oat shoots. The ability of these antisera to precipitate phytochrome from green oats was independent of the size of phytochrome used for immunization. While crude antisera immunoprecipitated as much as 80% of the phytochrome isolated from green oat shoots, antibodies immunopurified from these sera with a column of highly purified, approx. 120-kDa phytochrome from etiolated oats precipitated no more than about 5-10%. PMID- 24232328 TI - Sensitivity to far-red radiation in stomata of Phaseolus vulgaris L.: Rhythmic effects on conductance and photosynthesis. AB - The influence of far-red (FR; 700-800 nm) radiation on steady-state stomatal conductance and net photosynthesis in P. vulgaris has been studied. Whereas FR radiation alone was relatively ineffective, addition of FR to a background of white light (WL; predominantly 400-700 nm) resulted in increased stomatal conductance. Stomata exhibited a marked diurnal sensitivity to FR. The action maximum for enhancing stomatal conductance was near 714 nm. A combination of FR and infra-red (IR; >800 nm) enhanced net photosynthesis when added to a background of WL. When IR alone was added to WL, there was a net decrease in photosynthesis, indicating that it is the FR waveband which is responsible for the observed photosynthetic effects. Naturally occurring levels of FR radiation (235 MUmol.m(-2).s(-1)) in vegetation-canopy shade enhanced net photosynthetic CO2 gain by 28% when added to a background of 55 MUmol.m(-2).s(-1) WL. PMID- 24232329 TI - Glucose uptake by symbiotic Chlorella in the green-hydra symbiosis. AB - There is a correlation between the ability of symbiotic Chlorella algae to take up glucose and their survival in green hydra grown in continuous darkness. Although normal symbionts of European green hydra, which persist at a stable level in dark-grown animals, possessed no detectable constitutive ability to take up glucose when grown in light, uptake was induced after incubation in a medium containing glucose. Further, symbionts isolated from hydra grown in darkness for two weeks had acquired a constitutive uptake ability. Neither NC64A nor 3N813A strains of algae, in artificial symbiosis with hydra, persisted in dark-grown animals, and they showed little or no uptake ability, although in culture NC64A possessed both constitutive and inducible glucose-uptake mechanisms. In contrast, mitotic indices in all three types of algae in symbiosis with hydra increased after host feeding, indicating that the factor which stimulates algal cell division is not identical to the substrate utilised during heterotrophic growth. PMID- 24232330 TI - Periodicity of response to abscisic acid in lateral buds of willow (Salix viminalis L.). AB - Aseptically cultured lateral buds of Salix viminalis L. collected from field grown trees exhibited a clear periodicity in their ability to respond to exogenous abscisic acid (ABA). Buds were kept unopened by ABA only when the plants were dormant or entering dormancy. Short days alone did not induce bud dormancy in potted plants but ABA treatment following exposure to an 8-h photoperiod prevented bud opening although ABA treatment of buds from long-day plants did not. Naturally dormant buds taken from shoots of field-grown trees and cultured in the presence of ABA opened following a chilling treatment. In no cases were the induction and breaking of dormancy and response to ABA correlated with endogenous ABA levels in the buds. PMID- 24232331 TI - Control of CO2 fixation regulation of stromal fructose-1,6-bisphosphatase in spinach by pH and Mg(2+) concentration. AB - The effect of pH and of Mg(2+) concentration on the light activated form of stromal fructose-1,6-bisphosphatase (FBPase) was studied using the enzyme rapidly extracted from illuminated spinach chloroplasts. The (fructose-1,6-bisphosphate(4 ))(Mg(2+)) complex has been identified as the substrate of the enzyme. Therefore, changes of pH and Mg(2+) concentrations have an immediate effect on the activity of FBPase by shifting the pH and Mg(2+) dependent equilibrium concentration of the substrate. In addition, changes of pH and Mg(2+) concentration in the assay medium have a delayed effect on FBPase activity. A correlation of the activities observed using different pH and Mg(2+) concentrations indicates, that the effect is not a consequence of the pH and Mg(2+) concentration as such, but is caused by a shift in the equilibrium concentration of a hypothetical inhibitor fructose-1,6 bisphosphate(3-) (uncomplexed), resulting in a change of the activation state of the enzyme. The interplay between a rapid effect on the concentration of the substrate and a delayed effect on the activation state enables a rigid control of stromal FBPase by stromal Mg(2+) concentrations and pH. Fructose-1,6 bisphosphatase is allosterically inhibited by fructose-6-phosphate in a sigmoidal fashion, allowing a fine control of the enzyme by its product. PMID- 24232332 TI - The midday depression of CO2 assimilation in leaves of Arbutus unedo L.: diurnal changes in photosynthetic capacity related to changes in temperature and humidity. AB - Parts of attached leaves of the sclerophyllous shrub Arbutus unedo were subjected to simulated mediterranean days. Gas exchange was recorded in order to recognize the causes of the midday depression in CO2 assimilation. Depressions could be induced in part of a leaf: they were local responses. The CO2-saturation curves of photosynthesis, determined during the morning and afternoon maxima of CO2 assimilation and during the minimum at midday, established that depressions in CO2 assimilation were in one-half of the investigated cases totally caused by reversible reductions in the photosynthetic capacity of the leaves, and in the other half almost totally caused by such reductions. An analysis of 37 daily courses showed that morning reductions and afternoon recoveries of stomatal conductance and rate of photosynthesis occurred simultaneously and in proportion to each other, with the result that the partial pressure of CO2 in the intercellular spaces remained more or less constant. Midday depressions occurred also in detached leaves standing in water. The initiation of a midday depression was not caused by a circadian rhythm, nor was high quantum flux or high temperature a requirement. There was no correlation between the rate of water loss from the leaves, or the amount of water lost, with the degree of reduction of the photosynthetic capacity. However, depressions occurred if an apparent threshold in the water-vapor pressure difference between leaf and air was exceeded. This critical value varied between about 20 and 30 mbar, depending on the leaf investigated. The dominating role of humidity in the induction of the midday depression was further demonstrated when leaf temperature was held constant and the vapor-pressure difference was made to follow the pattern of the mediterranean day: depressions occurred. Depressions however were hardly noticeable when the water-vapor pressure difference was held constant and leaf temperature was allowed to vary. In another set of experiments, leaves were subjected to variations in temperature and humidity independent of the time of the day, under otherwise constant conditions. Photosynthetic capacity and stomatal conductance proved to be almost insensitive to changes in temperature (in a range extending from 20 to 37 degrees C) as long as the water vapor pressure difference was held constant. If it was not, the rate of photosynthesis began to decline with increasing temperature after a threshold water-vapor pressure difference was exceeded. The position of the resulting apparent temperature optimum of photosynthesis depended on the humidity of the air. We suggest that the ability of A. unedo to respond to a dry atmosphere with a reversible reduction of its photosynthetic capacity (by a still unknown mechanism) is the result of a co-evolution with the development of a strong stomatal sensitivity to changes in humidity. PMID- 24232333 TI - Abscisic acid metabolism -vacuolar/extravacuolar distribution of metabolites. AB - The biotransformation of abscisic acid (ABA) was studied in cell suspension cultures of Lycopersicon esculentum. The ABA was converted by the cells to phaseic acid, nigellic acid, dihydrophaseic acid, abscisic acid-beta-D glucopyranosyl ester (ABA-Glc) and other ABA and phaseic acid conjugates. Investigation of their cellular distribution showed that the conjugated forms were located only in the vacuoles whereas ABA and its acidic metabolites were found mainly in the extravacuolar fractions. Our results, together with a number of studies on the increase of ABA-Glc as a response to stress, allow us to propose that ABA-Glc is irreversibly compartmented in the vacuoles of plant cells. PMID- 24232334 TI - Nitrogen supply as a factor influencing photoinhibition and photosynthetic acclimation after transfer of shade-grown Solanum dulcamara to bright light. AB - We have compared the ability of shadegrown clones of Solamum dulcamara L. from shade and sun habitats to acclimate to bright light, as a function of nitrogen nutrition before and after transfer to bright light. Leaves of S. dulcamara grown in the shade with 0.6 mM NO 3 (-) have similar photosynthetic properties as leaves of plants grown with 12.0 mM NO 3 (-) . When transferred to bright light for 1-2 d the leaves of these plants show substantial photoinhibition which is characterized by about 50% decrease in apparent quantum yield and a reduction in the rate of photosynthesis in air at light saturation. Photoinhibition of leaf photosynthesis is associated with reduction in the variable component of low temperature fluorescence emission, and with loss of in-vitro electron transport, especially of photosystem II-dependent processes.We find no evidence for ecotypic differentiation in the potential for photosynthetic acclimation among shade and sun clones of S. dulcamara, or of differentiation with respect to nitrogen requirements for acclimation. Recovery from photoinhibition and subsequent acclimation of photosynthesis to bright light only occurs in leaves of plants provided with 12.0 mM NO 3 (-) . In these, apparent quantum yield is fully restored after 14 d, and photosynthetic acclimation is shown by an increase in light-saturated photosynthesis in air, of light-and CO2-saturated photosynthesis, and of the initial slope of the CO2-response curve. The latter changes are highly correlated with changes in ribulose-bisphosphate-carboxylase activity in vitro. Plants supplied with 0.6 mM NO 3 (-) show incomplete recovery of apparent quantum yield after 14 d, but CO2-dependent leaf photosynthetic parameters return to control levels. PMID- 24232335 TI - Calcium acetate induces calcium uptake and formation of calcium-oxalate crystals in isolated leaflets of Gleditsia triacanthos L. AB - During treatment of isolated, peeled leaflets of Gleditsia triacanthos with 0.5-2 mM [(45)Ca]acetate, saturation of the cell-wall free space with Ca(2+) occurred within 10 min and was followed by a period of 6-10 h during which there was no significant Ca-uptake into the protoplast, but apoplastic Ca(2+) was periodically released into the medium. Later, Ca(2+) was absorbed for 3-4 d at rates of up to 2.2 MUmol Ca(2+).h(-1).(g FW)(-1) to final concentrations of 350 MUmol Ca(2+). (g FW)(-1). The distribution of absorbed Ca(2+) between cell wall, vacuole and Ca oxalate crystals was determined during Ca-uptake. Wheras intact, cut leaflets deposited absorbed Ca(2+) as Ca-oxalate in the crystal cells, peeled leaflets lacking crystal cells accumulated at least 40-50 MUmol.(g FW)(-1) soluble Ca(2+) before the absorbed Ca(2+) was precipitated as Ca-oxalate. These observations indicate that the mechanisms for the continuous uptake of Ca(2+), the synthesis of oxalate and the precipitation of Ca(2+) as Ca-oxalate are operational in the crystal cells of intact leaflets, but not in the mesophyll cells of peeled leaflets where they must be induced by exposure to Ca(2+). The precipitation of absorbed Ca(2+) as Ca-oxalate by the crystal cells of isolated Gleditsia leaflets illustrates the role of these cells in the excretion of surplus Ca(2+) which enters normal, attached leaves with the transpiration stream.In addition to acetate, only Ca-lactate and Ca-carbonate lead to Ca-uptake, but at rates well below those observed with Ca-acetate. Other small organic anions (citrate, glycolate, glyoxalate, malate) and inorganic anions (chloride, nitrate, sulfate) did not permit Ca-uptake. Acetate-(14)C was rapidly absorbed during Ca-uptake, but less than 20% was incorporated into Ca-oxalate; the rest remained mostly in the soluble fraction or was metabolized to CO2. Acetate, as a permeable weak acid, may enable rapid Ca-uptake by stimulating proton extrusion at the plasmalemma and by serving as a counterion during Ca-accumulation in the vacuole, but is unlikely to function as the principal substrate for oxalate synthesis. PMID- 24232336 TI - Urease in jack-bean (Canavalia ensiformis (L.) DC) seeds is a cytosolic protein. AB - Urease (EC 3.5.1.5) is abundantly present in the seeds of many species of Leguminosae. There is at present conflicting information in the literature about its subcellular location and status as a glycoprotein. We have made a study of the subcellular location of urease in jack-bean cotyledons using an immunocytochemical approach; in addition, we studied the biosynthesis and glycoprotein nature of the enzyme using several biochemical approaches. All the results are in agreement with the interpretation that the seed urease is not a glycoprotein, is synthesized on free polysomes, and is present in the cytosol of the storage parenchyma cells. PMID- 24232337 TI - Genetic control of UDP-glucose: anthocyanin 5-O-glucosyltransferase from flowers of Matthiola incana R.Br. AB - In flower extracts of defined genotypes of Matthiola incana, an enzyme was demonstrated which catalyzes the transfer of the glucosyl moiety of uridine 5' diphosphoglucose (UDPGlc) to the 5-hydroxyl group of pelargonidin and cyanidin 3 glycosides and acylated derivatives. The best substrate for 5-glucosylation is the 3-xylosylglucoside acylated with p-coumarate, followed by the 3 xylosylglucoside and by the acylated (p-coumarate) 3-glucoside. The 3-glucoside itself is a very poor substrate. Besides UDPGlc, thymine 5'-diphosphoglucose is a suitable glucosyl-donor, but with a reduced reaction rate (42%). The anthocyanin 5-O-glucosyltransferase exhibits a pH optimum at 7.5 and is generally inhibited by divalent ions and by ethylenediaminetetraacetic acid and p chloromercuribenzoate. Investigations on different genotypes showed that the 5-O glucosyltransferase activity is clearly controlled by the gene l. In confirmation of earlier chemogenetic work, enzyme activity is only present in lines with the wild-type allele l(+). The anthocyanin 5-O-glucosyltransferase activity is strictly correlated with the formation of 5-glucosylated anthocyanins during bud development. PMID- 24232338 TI - Tobacco-mosaic-virus-induced increase in abscisic-acid concentration in tobacco leaves: : Intracellular location in light and dark-green areas, and relationship to symptom development. AB - The concentrations of free and bound abscisic acid (ABA and the presumed ABA glucose ester) increased three- to fourfold in leaves of White Burley tobacco (Nicotiana tabacum L.) systemically infected with tobacco mosaic virus. Infected leaves developed a distinct mosaic of light-green and dark-green areas. The largest increases in both free and bound ABA occurred in dark-green areas. In contrast, virus accumulated to a much higher concentration in light-green tissue. Free ABA in healthy leaves was contained predominantly within the chloroplasts while the majority of bound ABA was present in non-chloroplastic fractions. Chloroplasts from light-green or dark-green tissues were able to increase stromal pH on illumination by an amount similar to chloroplasts from healthy leaf. It is unlikely therefore that any virus-induced diminution of pH gradient is responsible for increased ABA accumulation. Tobacco mosaic virus infection had little effect on free ABA concentration in chloroplasts; the virus-induced increase in free ABA occurred predominantly out-side the chloroplast. The proportional distribution of bound ABA in the cell was not changed by infection. Treatment of healthy plants with ABA or water stress increased chlorophyll concentration by an amount similar to that induced by infection in dark-green areas of leaf. A role for increased ABA concentration in the development of mosaic symptoms is suggested. PMID- 24232339 TI - Genetic diversity among sublines originating from a single somatic hybrid cell of Duboisia hopwoodii + Nicotiana tabacum. AB - The genetic instability of an intertribal hybrid cell line, Duboisia hopwoodii + Nicotiana tabacum, obtained by mechanical isolation of a single hybrid cell was studied. Ten subclones of calli derived from this hybrid cell line were cultured for 3 years, and their genetic makeup clarified as to nuclear DNA content, chromosome constitution, and peroxidase isozymes. Nuclear DNA content differed in each subclone. In most subclones, mean DNA content was lower than the mean DNA content in the original hybrid cell line determined 1 year after fusion. This decrease in DNA content is partly attributable to the elimination of tobacco chromosomes that occurred in all subclones. The extent to which tobacco chromosomes were eliminated varied among the subclones - evidence that chromosome elimination occurred slowly. Peroxidase isozyme analysis indicated the loss of a tobacco-specific isozyme, thus confirming results obtained by chromosome analysis. Shoots regenerated from two hybrid subclones after 2 years were also heterogeneous in morphology and nuclear DNA content. PMID- 24232340 TI - Recombination in sesquidiploid hybrids of Lycopersicon esculentum * Solanum lycopersicoides and derivatives. AB - Sesquidiploid hybrids of L. esculentum (L) x S. lycopersicoides (S) were backcrossed to L via L. pennellii (P) as a bridging species in order to detect and measure recombination. Although use of P injected its traits into the populations, the investigated traits were proven to originate from S. The appearance of S traits in diploids in the immediate progeny of sesquidiploids but mainly of derived alien addition types proved the occurrence of recombination at rates varying from 1.6% to 16%. In subsequent BC's, these traits were inherited in dominant Mendelian fashion, except for deviations favoring recurrent parent alleles, sometimes with highly significant deviations from 1?1. Inheritance was investigated in BC and F2 ex BC for 13 traits with strong phenotypic modifications of morphological, physiological, and isozymic nature. Monogenic determination was confirmed in most instances by tight linkages. For most of the traits, small progenies allowed only rough estimates of linkage intensities, but for Wa (gene for White anthers, universal in S), a test cross with four markers on chromosome 8 established its locus 2 cM distal to dl, proximally on 8L. Also noteworthy is the linkage of Dls, a gene determining sensitivity of flowering to long days, close to sp, situated subterminally on 6L. For the majority of traits, these manifestations of linkage proved that the appearance of S traits resulted from recombination, not alien chromosome substitution - a conclusion also reinforced by observations of chromosome pairing in alien addition types and diploid derivatives. Recombined S alleles have loci in various chromosome positions. Although they were discovered on the shorter chromosomes (nos. 6-12), hybridization barriers precluded tests with the longer chromosomes. Thus, no evidence was found for restriction of recombination to certain chromosomes or chromosomal regions. The prospects therefore appear favorable for deriving valuable traits from the S parent. PMID- 24232342 TI - Diploid somatic-hybrid plants regenerated from rice cultivars. AB - Somatic hybrid plants were obtained between rice cultivars 'Yamahoushi' and 'Murasakidaikoku'. Since 'Murasakidaikoku' is a double mutant having both dominant (purple coloration) and recessive (dwarf) markers, the somatic hybrids can be easily distinguished from their parents. Protoplasts were isolated from anther-derived calli, and electrofused protoplasts were cultured without selection of hybrid cells. Out of 27 regenerated plants, 9 proved to be hybrids based on their purple coloration and normal plant type, traits which were identical to those of the sexual F1 hybrid between the same parental cultivars. The somatic hybrids included three diploid and six triploid plants. Segregation of parental markers was observed in the selfed progenies. These results demonstrated that diploid hybrids of rice could be obtained through somatic hybridization between haploid anther-derived cells instead of by sexual hybridization. PMID- 24232341 TI - Monosomic additions in beet (Beta vulgaris) carrying extra chromosomes of B. procumbens : 2. Effects of the alien chromosomes on in vivo and in vitro plant development. AB - Alien monosomic additions in beet (Beta vulgaris), each carrying one of the nine chromosomes of B. procumbens, were grown in vivo and in vitro to study the effect of the alien chromosomes on plant development. All additional chromosomes caused a reduction of the growth rate in vivo, which, in one case was so strong that some of the plants died as seedlings. In general, the morphological plant characteristics were not very useful to distinguish the addition types; this could have been the results of the wide variation in the recipient parent. However, some developmental characteristics proved to be highly chromosome specific; for plants in vivo this was annuality, in combination with early or late flowering. If grown in vitro, chromosome specificity was observed for growth type (rosette or elongated stem), occurrence and rate of vitrification, occurrence and morphology of wound callus, formation of additional meristems on the midribs of leaves, formation of roots and a specific reaction to benzylaminopurine (BAP) the medium. Two chromosome types of B. procumbens caused resistance to the beet cyst nematode. PMID- 24232343 TI - Dominance relationships among S-alleles in Corylus avellana L. AB - Pollen-stigma compatibility relationship were studied in 50 cultivars and more than 800 seedlings of the European hazelnut (Corylus avellana L.). A total of 22 unique S-alleles have been identified. Dominance relationships in 75 of the possible 231 pairs of alleles have been determined in both pistil and pollen. In the pistil, all alleles exhibited independent action, whereas in the pollen, alleles exhibited either dominance or codominance. The dominance relationship was linear with 7 levels of dominance. PMID- 24232344 TI - Structure of melon rDNA and nucleotide sequence of the 17-25S spacer region. AB - Restriction enzyme and hybridization analysis of melon nuclear DNA suggests a homogenous rDNA population with a repeat unit of 10.2 kb. Several full length Hind III rDNA repeat units were cloned and one of these is described in detail. The regions coding for 25S, 17S and 5.8S rRNAs were located by crossed-contact hybridization and R-loop mapping. Introns were not observed. The nucleotide sequence of the internal transcribed spacer and flanking regions was determined and compared with the corresponding region from rice rDNA by dot matrix analysis. In addition, the extent of gross sequence homology between cloned melon and pea rDNA units was determined by heteroduplex mapping. PMID- 24232345 TI - Complex interspecific hybridization in barley (Hordeum vulgare L.) and the possible occurrence of apomixis. AB - Several complex hybrids were produced from the combination [(Hordeum lechleri, 6x xH. procerum, 6 x) * H. vulgare, 2 x]. Crosses with six diploid barley lines resulted in triple hybrids, most of which had a full complement of barley chromosomes (no. 1-7), but were mixoploid with respect to alien chromosomes (19 22). In one combination, chromosome no. 7 was duplicated. Meiosis in triple hybrids showed low, but variable pairing (1.3-5.5 chiasmata per cell). The syndesis probably did not include the barley chromosomes. Direct back-crosses to di- and tetraploid barley lines were unsuccessful. Chromosome doubling of the triple hybrid based on cv 'Pallas' resulted in a plant with 2n = 53-56, which had an increased fertility. Backcrosses to one di- and one tetraploid barley line resulted in offspring. The cross made with the tetraploid line ('Haisa II'), produced a 28-chromosomic plant in which the male parental genome was absent. We suspect that this plant may have arisen through parthenogenetic development of a reduced female gamete. The other cross with a diploid line ('9208/9') resulted in plant with 2n = 51-53. The most likely explanation for this second plant is that an unreduced gamete from the amphiploid was fertilized by a normal gamete from the backcross parent, and during early embryo development, some chromosomes were eliminated. PMID- 24232346 TI - Isozyme variation and RFLPs at the beta-amylase loci in wheat. AB - Forty-one hexaploid wheat genotypes have been examined for RFLPs detected by a beta-amylase probe using three restriction enzymes, and for mature grain beta amylase isozyme polymorphism following IEF. The two homoeoallelic series assayed for RFLPs differed: little variation was found at group 2 chromosome homoeoloci, while the group 4/5 chromosome homoeoloci displayed considerable variation. Varieties that displayed a RFLP with one RE almost always did likewise with the other two REs, suggesting that most of the polymorphisms observed were due to large DNA rearrangements. Comparison of the variation in grain beta-amylase isozymes with the RFLP results indicated strong associations between particular RFLP and isozyme alleles. PMID- 24232347 TI - Action of natural selection in lines of Drosophila selected for a new level of canalization. AB - Four lines of Drosophila melanogaster previously selected for a stabilized phenotype of two extra dorsocentral bristles were examined for 20 generations of canalizing selection and relaxation of selection. A substantial frequency of flies with either two anterior or two posterior extra bristles was maintained in the relaxed lines. These patterns were the only ones tolerated by natural selection, i.e., the only symmetric ones. It was concluded that anterior and posterior dorsocentral bristles are two independent development structures, and the results are discussed in relation to two proposed genetic systems for bristle determination. PMID- 24232348 TI - The genomic relationship between Glycine max (L.) Merr. and G. soja Sieb. and Zucc. as revealed by pachytene chromosome analysis. AB - This study was conducted with the objective of determining the genomic relationship between cultivated soybean (Glycine max) and wild soybean (G. soja) of the subgenus Soja, genus Glycine. Observations on cross-ability rate, hybrid viability, meiotic chromosome pairing, and pollen fertility in F 1 hybrids of G. max * G. soja and reciprocals elucidated that both species hybridized readily and set mature putative hybrid pods, generated vigorous F1 plants, had a majority of sporocytes that showed 18II + 1IV chromosome association at diakinesis and metaphase I, and had a pollen fertility that ranged from 49.2% to 53.3%. A quadrivalent was often associated with the nucleolus, suggesting that one of the chromosomes involved in the interchange is a satellited chromosome. Thus, G. max and G. soja genetic stocks used in this study have been differentiated by a reciprocal translocation. Pachytene analysis of F1 hybrids helped construct chromosome maps based on chromosome length and euchromatin and heterochromatin distribution. Chromosomes were numbered in descending order of 1-20. Pachytene chromosomes in soybean showed heterochromatin distribution on either side of the centromeres. Pachytene analysis revealed small structural differences for chromosomes 6 and 11 which were not detected at diakinesis and metaphase I. This study suggests that G. max and G. soja carry similar genomes and validates the previously assigned genome symbol GG. PMID- 24232349 TI - DNA polymorphisms in commercial and wild strains of the cultivated mushroom, Agaricus bisporus. AB - DNA from the cultivated mushroom, Agaricus bisporus, was cloned into the bacteriophage lambda vector EMBL3 creating a partial genomic library. Ten random clones from the library were used to probe for restriction fragment length polymorphisms (RFLPs). Six of the ten probes detected polymorphisms and were used to demonstrate variation in wild and cultivated strains of the mushroom. These results suggest that RFLPs could form a basis for genetic finger-printing and subsequent strain protection in A. bisporus. In single spore progeny, RFLPs were used to demonstrate normal meiotic segregation and to differentiate between homokaryons and heterokaryons. RFLPs therefore have great potential in the development of the genetics and breeding of this commercially important species. PMID- 24232350 TI - Best linear prediction of breeding values in a forest tree improvement program. AB - Best Linear Prediction (BLP) was used to predict breeding values for 1,396 parents from progeny test data in an operational slash pine breeding program. BLP rankings of parents were compared to rankings of averaged standard scores, a common approach in forestry. Using BLP rankings, selection of higher ranking parents tends to choose parents in a larger number of more precise progeny tests. The trend is the opposite with standard scores; higher ranking parents tend to be those in fewer, less precise tests. BLP and a related methodology, Best Linear Unbiased Prediction (BLUP), were developed by dairy cattle breeders and have not been used widely outside of animal breeding for predicting breeding values from messy progeny test data. Application of either of these techniques usually requires simplifying assumptions to keep the problem computationally tractable. The more appropriate technique for a given application depends upon which set of assumptions are better for the given problem. An assumption of homogeneous genetic and error variances and covariances, generally made by animal breeders when applying BLUP, was inappropriate for our data. We employed an approach that treated fixed effects as known and treated the same trait measured in different environments as different traits with heterogeneous variance structures. As tree improvement programs become more complex, the ease with which BLP and BLUP handle messy data and incorporate diverse sources of information should make these techniques appealing to forest tree breeders. PMID- 24232351 TI - Genome specific, highly repeated sequences of Hordeum vulgare: cloning, sequencing and squash dot test. AB - Highly repeated sequences of nuclear DNA from barley Hordeum vulgare (L.) variety 'Erfa' were cloned. Several clones containing barley specific repeated DNA were analysed by sequence analysis and Southern blot hybridization. The investigated repeats differ from each other in their length, sequence and redundancy. Their length ranges from 36 bp to about 180 bp. The repeats are AT-rich and differ widely in their redundancy within the barley genome. Southern analysis showed that the repeats belong to different repetition complexes. The possibility for utilizing these clones as probes for simple and fast genome analysis is demonstrated in squash dot experiments. PMID- 24232352 TI - In vitro response as a reflection of genomic diversity in long-term cultures of Musa. AB - Ten commercial cultivars of Musa representing five different types of genomic constitutions were studied for in vitro multiplication through meristem culture. In addition, the effects of various genomic constitutions at different ploidy levels on growth and meristem proliferation in long-term cultures were analysed statistically. Plantlets were readily obtained by culturing the excised meristems on MS semisolid medium supplemented with IAA, IBA and BAP at various concentrations. The regenerative potential of all cultivars of Musa, irrespective of their genomes, remained unaffected in long-term culture, even after 28-30 months. The genomic influence on both the nature and rate of proliferative growth was evident. Statistical analysis revealed that the rates of meristem proliferation between different cultivars of the same passage and between different passages of the same cultivar were significantly different. Those cultivars having only an A genome showed a low rate of meristem proliferation, while under the same culture conditions, cultivars having one or two B genomes in addition to the A exhibited a very high rate. PMID- 24232353 TI - Natural selection of allozyme polymorphisms: a microgeographical differentiation by edaphic, topographical, and temporal factors in wild emmer wheat (Triticum dicoccoides). AB - Allozymic variation in proteins encoded by 47 loci was analyzed electrophoretically in 1983/4 and 1984/5 in 356 individual plants of wild emmer wheat, Triticum dicoccoides, from a microsite at Tabigha, north of the Sea of Galilee, Israel. Each year the test involved two 100-meter transects, each equally subdivided into basalt and terra rossa soil types, and comparisons were based on 16 common polymorphic loci. Significant genetic differentiation, genetic phase disequilibria, and genome organization according to soil type were found over very short distances. Our results suggest that allozyme polymorphisms in wild emmer wheat are partly adaptive, and that they differentiate at both single and multilocus structures primarily from environmental stress of such ecological factors as soil type, topography, and temporal changes, probably through aridity stress. PMID- 24232354 TI - Structure of the mitochondrial genome of Beta vulgaris L. AB - The structure of mitochondrial DNA (mt-DNA) from sugarbeet (Beta vulgaris L.) has been studied by biochemical methods and electron microscopy. It was found to be complex multipartite consisting of two main classes of molecules: high molecules weight (HMW) mtDNA and low molecular weight (LMW) mtDNA. The HMW mtDNA consists of rosette-like structures and globules resembling chromomeres (150-200nm). A typical rosette has a protein core and radially stemming closed DNA loops (from 0.6-1.5 MUm). The number of loops in a rosette varies from 16-30. The bulk of HMW mtDNAs are represented by interconnected rosettes (total contour length about 130 160 MUm, 403-496 kbp). Such large circular DNAs may be evidence of the master chromosome arrangement of the sugarbeet genome. Globules and rosettes are interconnected by thick and thin DNA fibrils, along which nucleosome- and nucleomere-like structures are distributed. The LWM mtDNA is composed of two groups of supercoiled circular molecules, 0,2-1.5 MUm and 0.02-0.05 MUm in size. Electrophoretic analysis demonstrated that LWM mtDNA is represented by minicircle plasmid-like DNA molecules of 1.3, 1.4 and 1.6 kbp. PMID- 24232355 TI - Intergeneric asymmetric hybrids between Nicotiana plumbaginifolia and Atropa belladonna obtained by "gamma-fusion". AB - Asymmetric nuclear hybrids have been obtained by fusion of cells from a nitrate reductase deficient mutant of Nicotiana plumbaginifolia (cnx20) and gamma irradiated protoplasts of Atropa belladonna (irradiation doses tested were 10, 30, 50 and 100 krad). The hybrid formation frequency following selection for genotypic complementation in the NR function was in the range of 0.7%-3.7%. Cytogenetic studies demonstrated that all hybrid plants tested possessed multiple (generally tetra- or hexaploid) sets of N. plumbaginifolia (n = 10) chromosomes along with 6-29 Atropa chromosomes (n = 36), some of which were greatly deleted. Besides the cnxA gene (the selection marker), additional material of the irradiated partner was expressed in some of the lines, as shown by analyses of multiple molecular forms of enzymes. Surprisingly, rDNA genes of both parental species were present and amplified in the majority of the hybrids. Whenever studied, the chloroplast DNA in the hybrids was derived from the Nicotiana parent. Regenerants from some lines flowered and were partially fertile. It is concluded that irradiation of cells of the donor parent before fusion can be used to produce highly asymmetric nuclear hybrid plants, although within the dose range tested, the treatment determined the direction of the elimination but not the degree of elimination of the irradiated genome. PMID- 24232356 TI - Genotype-independent leaf disc transformation of potato (Solanum tuberosum) using Agrobacterium tumefaciens. AB - Leaves of the in vitro grown potato cultivars 'Bintje', 'Berolina', 'Desiree', and 'Russet Burbank' were wounded and co-cultivated with Agrobacterium strains having chimeric bar and nptII genes on a disarmed T-DNA. Each leaf from these cultivars formed numerous calli on kanamycin-containing medium, and almost all calli regenerated shoots. For 'Russet Burbank', it was necessary to include AgNO3 in the medium to obtain efficient shoot regeneration. The transformed plants have one to a few copies of the T-DNA, show NPT-II and PAT activities, and are resistant to high doses of the commercial preparation of phospinotricin (glufosinate). Almost no somaclonal variation was detected in trans-genic plants. PMID- 24232357 TI - Juvenile body weight and gonad development in a diallel cross among lines of Japanese quail (Coturnix coturnix japonica). AB - The influence of growth on the extent of heterosis for juvenile body weight and gonad development was studied in a diallel cross among two lines of Japanese quail differing in adult body size. A total of 1,096 birds (563 males and 533 females) was slaughtered between 25 and 49 days of age. Reciprocal cross differences were non-significant. Heterosis showed a curvilinear course with age peaking during early growth (body weight) and during sexual maturity (gonad percentage). Overall advanced physiological development of the crossbreds probably begins as early as during the embryonic stages and results in earlier sexual maturity. In females, heterosis for percentage gonads was biased strongly by the presence of a hard-shelled egg in the uterus. PMID- 24232358 TI - Chromosomal location by F1 monosomic analysis of endosperm proteins in bread wheat : 1. One-dimensional electrophoresis of glutenins and gliadins. AB - A new methodology to determine the chromosomal location and allelic differences of endosperm proteins in common wheat cultivars by analysis of monosomic intervarietal hybrids is reported. Endosperm proteins from the common wheats Chinese Spring, Capelle Desprez, Holdfast and Pane 247 are studied using monosomic F1 for the chromosomes of homoeologous groups 1 and 6. The proteins were fractionated by two electrophoretical techniques, SDS- and A-PAGE. The use of monosomic offers a remarkable advantage over the utilization of intervarietal substitution lines, because it permits a quicker characterization and earlier evaluation of basic material to be used in breeding programmes. PMID- 24232359 TI - Using clonal replicates to explore genetic variation in a perennial plant species. AB - An experimental design is presented for estimating genetic parameters using a family structure with clonally replicated individuals. This experimental design provides a technique to quantify genetic variation in a population, with partial separation of additive, dominance and epistatic gene action. Our method is offered as an alternative to techniques for estimating epistatic gene action that require several generations and/or inbreeding. Such methods are not particularly useful for long-lived perennials with long generation cycles. An example of the analysis is given with a forest tree species, Populus deltoides Bartr., and parameter estimates are presented for traits measured over 8 years. PMID- 24232360 TI - Biochemical genetics of powdery mildew resistance in pea. AB - A biochemical study on phenolic (total phenols and orthodihydroxy phenols) content and on the activities of phenol oxidizing enzymes (peroxidase and polyphenol oxidase) in pea cultivars resistant and susceptible to powdery mildew infection revealed that the resistant cultivars contained higher levels of phenolics and phenol-oxidizing enzymes than the susceptible ones. A further study of their F1s, F2s and backcross progenies suggested a high heritability for all biochemical traits. The correlation coefficients between the biochemical parameters and the disease index were also high. Both additive (d) and dominant (h) components were found to contribute to the inheritance of these constituents. PMID- 24232362 TI - A randomized feasibility study of a 12-week community-based exercise program for people with Huntington's disease. AB - BACKGROUND AND PURPOSE: The beneficial role of exercise as a treatment approach in Huntington's disease (HD) has support from both preclinical work and small scale studies; however, there have been no controlled studies of gym-based exercise in people with HD. This phase 2 randomized trial (ISRCTN 59910670) assessed feasibility, safety, acceptability, and benefit of a structured exercise program. METHODS: Thirty-one participants (16 men; mean [SD] age = 50.4 [11.4] years) were randomly allocated to intervention (n = 16) or control group (usual care; n = 15). The intervention entailed a weekly supervised gym session of stationary cycling and resistance exercises, and a twice weekly independent home based walking program. Retention and adherence rates and adverse events were recorded. Acceptability was determined from subjective reports of tolerability and physiological measures recorded during the gym sessions. Assessment of benefit included measures of physical abilities, disease severity, and quality of life (36-Item Short Form Health Survey). Analysis of covariance was used to test outcomes of interest. RESULTS: The retention rate was 81% (9 of the 11 individuals who started the intervention completed it) and of the 9 who completed the program, 7 attended more than 75% (9/12) of the gym sessions. There were no related adverse events and the intervention was well tolerated by most participants. The between-group effect estimate for the Mental Component Summary score of the 36-Item Short Form Health Survey (n = 9; intervention, n = 13; control) was 7 (95% CI: 0.4-13.7) Moderate effect sizes for cognitive outcomes and measures of walking were also observed. DISCUSSION AND CONCLUSIONS: Observed effect sizes for clinical outcomes suggest the structured exercise program has benefit for persons with HD; larger scale trials are warranted.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A60) for more insights from the authors. PMID- 24232361 TI - The role of the insulin-like growth factor (IGF) axis in osteogenic and odontogenic differentiation. AB - The insulin-like growth factor (IGF) axis is a multicomponent molecular network which has important biological functions in the development and maintenance of differentiated tissue function(s). One of the most important functions of the IGF axis is the control of skeletal tissue metabolism by the finely tuned regulation of the process of osteogenesis. To achieve this, the IGF axis controls the activity of several cell types-osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts to achieve the co-ordinated development of appropriate hard tissue structure and associated matrix deposition. In addition, there is an increasing awareness that the IGF axis also plays a role in the process of odontogenesis (tooth formation). In this review, we highlight some of the key findings in both of these areas. A further understanding of the role of the IGF axis in hard tissue biology may contribute to tissue regeneration strategies in cases of skeletal tissue trauma. PMID- 24232363 TI - Video games and rehabilitation: using design principles to enhance engagement in physical therapy. AB - Patient nonadherence with therapy is a major barrier to rehabilitation. Recovery is often limited and requires prolonged, intensive rehabilitation that is time consuming, expensive, and difficult. We review evidence for the potential use of video games in rehabilitation with respect to the behavioral, physiological, and motivational effects of gameplay. In this Special Interest article, we offer a method to evaluate effects of video game play on motor learning and their potential to increase patient engagement with therapy, particularly commercial games that can be interfaced with adapted control systems. We take the novel approach of integrating research across game design, motor learning, neurophysiology changes, and rehabilitation science to provide criteria by which therapists can assist patients in choosing games appropriate for rehabilitation. Research suggests that video games are beneficial for cognitive and motor skill learning in both rehabilitation science and experimental studies with healthy subjects. Physiological data suggest that gameplay can induce neuroplastic reorganization that leads to long-term retention and transfer of skill; however, more clinical research in this area is needed. There is interdisciplinary evidence suggesting that key factors in game design, including choice, reward, and goals, lead to increased motivation and engagement. We maintain that video game play could be an effective supplement to traditional therapy. Motion controllers can be used to practice rehabilitation-relevant movements, and well designed game mechanics can augment patient engagement and motivation in rehabilitation. We recommend future research and development exploring rehabilitation-relevant motions to control games and increase time in therapy through gameplay.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A61) for more insights from the authors. PMID- 24232364 TI - Treatment of severe hand impairment following stroke by combining assisted movement, muscle vibration, and biofeedback. AB - BACKGROUND AND PURPOSE: Few studies have addressed the rehabilitation of hand function in persons with severe impairment following stroke, and few therapeutic options are available for treatment. We investigated whether an intervention of robot-assisted movement and muscle vibration could reduce impairment and enable hand-opening to a greater extent when combined with torque biofeedback or electromyographic (EMG) biofeedback. METHODS: Forty-three participants with severe hand impairment due to chronic stroke (>=1 year poststroke) were randomized to 1 of 2 treatment groups receiving assisted movement and muscle vibration combined with either torque or EMG biofeedback. Each participant received 30 sessions (30 minutes duration per session) directed at the impaired hand over 10 to 12 weeks. Outcomes were assessed using the Upper Extremity Fugl Meyer Assessment (UE-FMA), Stroke Impact Scale, and Box-and-Block Test scores. RESULTS: Twenty-eight of 43 participants had no baseline finger extension; the remainder had an average of 23 +/- 26 mm extension in the most active finger. Assisted movement and muscle vibration were associated with a significant increase in all outcome measures across both treatment groups, and for the UE-FMA and Stroke Impact Scale within treatment groups, with no significant difference between groups. Based on the Box-and-Block Test scores, the assisted movement and muscle vibration intervention did not restore functional hand-opening to participants with baseline UE-FMA scores less than 17/66, regardless of the form of biofeedback. DISCUSSION AND CONCLUSIONS: Assisted movement and muscle vibration, combined with either EMG or torque biofeedback, appears to reduce upper limb impairment, improve volitional activation of the hand muscles, and restore a modicum of hand function in some persons with severe hand impairment due to chronic stroke.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A64) for more insights from the authors. PMID- 24232366 TI - On the catalytic mechanism of polysaccharide lyases: evidence of His and Tyr involvement in heparin lysis by heparinase I and the role of Ca2+. AB - The structurally diverse polysaccharide lyase enzymes are distributed from plants to animals but share common catalytic mechanisms. One, heparinase I (F. heparinum), is employed in the production of the major anticoagulant drug, low molecular weight heparin, and is a mainstay of cell surface proteoglycan analysis. We demonstrate that heparinase I specificity and efficiency depend on the cationic form of the substrate. Ca(2+)-heparin, in which alpha-L-iduronate-2 O-sulfate residues adopt (1)C4 conformation preferentially, is a substrate, while Na(+)-heparin is an inhibitor. His and Tyr residues are identified in the catalytic step and a model based on molecular dynamics and docking is proposed, in which deprotonated His203 initiates beta-elimination by abstracting the C5 proton of the alpha-L-iduonate-2-O-sulfate residue in the substrate, and protonated Tyr357 provides the donor to the hexosamine leaving group. PMID- 24232368 TI - Serum biomarkers in head and neck squamous cell cancer. AB - IMPORTANCE: Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials. OBJECTIVE: To determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers. DESIGN, SETTING, AND PARTICIPANTS: A retrospective experimental laboratory study at Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx. INTERVENTIONS: Following institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study. MAIN OUTCOMES AND MEASURES: The main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN) gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor. RESULTS: The serum samples of patients with HNSCC contained lower levels of IFN-gamma (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; P = .004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; P = .02), and macrophage inflammatory protein-1beta (MIP-1beta) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; P = .004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; P = .04). All other markers tested were not significantly different between patients with cancer and controls. CONCLUSIONS AND RELEVANCE: This pilot study demonstrated a significant decrease in serum IFN-gamma, IL-13, and MIP-1beta levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality. PMID- 24232369 TI - Surgical therapies for fecal incontinence. AB - PURPOSE OF REVIEW: Fecal incontinence is a significant source of morbidity and decreased quality of life (QOL) for many. Until recent years, few therapies beyond medical management were available for patients. Surgical treatment of fecal incontinence has evolved from colostomy and direct repair of muscle defects to interventional techniques such as nerve stimulation and bulking agents. We review the most recent surgical options for the treatment of fecal incontinence within the context of established therapies. RECENT FINDINGS: Overlapping sphincteroplasty is an established therapy that improves continence and QOL, although results deteriorate over time. Implanted artificial bowel sphincter has a 100% complication rate and 80% are explanted over time. Sacral nerve stimulation has minimal risk and more durable long-term improvement in continence. Less invasive versions of nerve stimulation are being researched. Injectable biomaterials have shown some promise, although durability of results is not clear. Novel therapies, including muscle cell transfer and pelvic slings are currently being investigated. SUMMARY: Surgical therapies for fecal incontinence continue to evolve and show promise in improving QOL with a lower risk profile. Effective valuation of these therapies is currently limited by heterogeneous studies, short duration of follow up, and inconsistent outcome measures. PMID- 24232372 TI - Target identification: Blocking vasopressin receptors reduces jet lag. PMID- 24232370 TI - Epidemiology of human noroviruses and updates on vaccine development. AB - PURPOSE OF REVIEW: Noroviruses (NoVs) are the most common cause of epidemic and sporadic cases of acute gastroenteritis worldwide. This review summarizes recent NoV disease burden estimates, epidemiology findings and provides an update on virus-like particle (VLP) vaccine studies. RECENT FINDINGS: NoVs are the leading cause of food-borne gastroenteritis and are replacing rotavirus as the predominant gastrointestinal pathogen in pediatric populations. Genogroup II, genotype 4 NoVs (GII.4) remain the dominant genotype worldwide. Increased NoV activity reported in late 2012 was associated with the emergence of a new GII.4 variant called Sydney 2012. New studies suggest that human NoVs can bind a larger range of histoblood group antigens, a susceptibility factor for NoV illness, thus expanding the susceptible population pool for infection. Intranasal immunization with a monovalent GI NoV VLP vaccine showed proof-of-concept efficacy. Studies using intramuscular immunization with a bivalent formulation including GII.4 VLPs are now underway. SUMMARY: The importance of NoVs as a major gastrointestinal pathogen underscores the need for well tolerated and effective vaccines. Results of VLP vaccine trials appear promising. However, the rapid evolution of NoV genotypes through antigenic drift and changing glycan specificities provide new challenges to epidemiology studies and vaccine trials. PMID- 24232373 TI - The value of single-pathogen antibacterial agents. PMID- 24232374 TI - Neurodegenerative disease: Tau immunotherapy targets transcellular propagation. PMID- 24232375 TI - Autoimmune disease: Parkinson's drug promotes myelin repair. PMID- 24232377 TI - The risks of risk aversion in drug regulation. AB - Drugs are approved by regulatory agencies on the basis of their assessment of whether the available evidence indicates that the benefits of the drug outweigh its risks. In recent years, regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, which reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before drug approval. The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent. Here, we discuss the consequences of regulatory risk-aversion for public health and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health. PMID- 24232376 TI - Histone lysine demethylases as targets for anticancer therapy. AB - It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small molecule inhibitors of these enzymes. PMID- 24232378 TI - Human pluripotent stem cell models of autism spectrum disorder: emerging frontiers, opportunities, and challenges towards neuronal networks in a dish. AB - Autism spectrum disorder (ASD) is characterized by deficits in language development and social cognition and the manifestation of repetitive and restrictive behaviors. Despite recent major advances, our understanding of the pathophysiological mechanisms leading to ASD is limited. Although most ASD cases have unknown genetic underpinnings, animal and human cellular models of several rare, genetically defined syndromic forms of ASD have provided evidence for shared pathophysiological mechanisms that may extend to idiopathic cases. Here, we review our current knowledge of the genetic basis and molecular etiology of ASD and highlight how human pluripotent stem cell-based disease models have the potential to advance our understanding of molecular dysfunction. We summarize landmark studies in which neuronal cell populations generated from human embryonic stem cells and patient-derived induced pluripotent stem cells have served to model disease mechanisms, and we discuss recent technological advances that may ultimately allow in vitro modeling of specific human neuronal circuitry dysfunction in ASD. We propose that these advances now offer an unprecedented opportunity to help better understand ASD pathophysiology. This should ultimately enable the development of cellular models for ASD, allowing drug screening and the identification of molecular biomarkers for patient stratification. PMID- 24232380 TI - Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers. AB - INTRODUCTION: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm(2) versus 12.5-15.7 cm(2)). STUDY DESIGN AND METHODS: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B). RESULTS: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo. CONCLUSION: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research. PMID- 24232379 TI - Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis. AB - PURPOSE: Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis. METHODS: We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7% of PG lyophilized mashed totum (OVX PGt), or 9.6% of PG fresh juice (OVX PGj) or 2.9% of PG lyophilized mashed peel (OVX PGp). RESULTS: As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced. CONCLUSION: These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status. PMID- 24232381 TI - Flow cytometric analysis of pollen grains collected from individual bees provides information about pollen load composition and foraging behaviour. AB - BACKGROUND AND AIMS: Understanding the species composition of pollen on pollinators has applications in agriculture, conservation and evolutionary biology. Current identification methods, including morphological analysis, cannot always discriminate taxa at the species level. Recent advances in flow cytometry techniques for pollen grains allow rapid testing of large numbers of pollen grains for DNA content, potentially providing improved species resolution. METHODS: A test was made as to whether pollen loads from single bees (honey-bees and bumble-bees) could be classified into types based on DNA content, and whether good estimates of proportions of different types could be made. An examination was also made of how readily DNA content can be used to identify specific pollen species. KEY RESULTS: The method allowed DNA contents to be quickly found for between 250 and 9391 pollen grains (750-28 173 nuclei) from individual honey-bees and between 81 and 11 512 pollen grains (243-34 537 nuclei) for bumble-bees. It was possible to identify a minimum number of pollen species on each bee and to assign proportions of each pollen type (based on DNA content) present. CONCLUSIONS: The information provided by this technique is promising but is affected by the complexity of the pollination environment (i.e. number of flowering species present and extent of overlap in DNA content). Nevertheless, it provides a new tool for examining pollinator behaviour and between-species or cytotype pollen transfer, particularly when used in combination with other morphological, chemical or genetic techniques. PMID- 24232382 TI - Campanulaceae: a family with small seeds that require light for germination. AB - BACKGROUND AND AIMS: The Campanulaceae is a large cosmopolitan family, but is understudied in terms of germination, and seed biology in general. Small seed mass (usually in the range 10-200 ug) is a noteworthy trait of the family, and having small seeds is commonly associated with a light requirement. Thus, the purpose of this study was to investigate the effect of light on germination in 131 taxa of the Campanulaceae family, from all five continents of its distribution. METHODS: For all taxa, seed germination was tested in light (8 or 12 h photoperiod) and continuous darkness under constant and alternating temperatures. For four taxa, the effect of light on germination was examined over a wide range of temperatures on a thermogradient plate, and the possible substitution of the light requirement by gibberellic acid and nitrate was examined in ten taxa. KEY RESULTS: For all 131 taxa, seed germination was higher in light than in darkness for every temperature tested. Across species, the light requirement decreased significantly with increasing seed mass. For larger seeded species, germination in the dark reached higher levels under alternating than under constant temperatures. Gibberellic acid promoted germination in darkness whereas nitrates partially substituted for a light requirement only in species showing some dark germination. CONCLUSIONS: A light requirement for germination, observed in virtually all taxa examined, constitutes a collective characteristic of the family. It is postulated that smaller seeded taxa might germinate only on the soil surface or at shallow depths, while larger seeded species might additionally germinate when buried in the soil if cued to do so by fluctuating temperatures. PMID- 24232383 TI - Autotetraploids of Vicia cracca show a higher allelic richness in natural populations and a higher seed set after artificial selfing than diploids. AB - BACKGROUND AND AIMS: Despite the great importance of autopolyploidy in the evolution of angiosperms, relatively little attention has been devoted to autopolyploids in natural polyploid systems. Several hypotheses have been proposed to explain why autopolyploids are so common and successful, for example increased genetic diversity and heterozygosity and the transition towards selfing. However, case studies on patterns of genetic diversity and on mating systems in autopolyploids are scarce. In this study allozymes were employed to investigate the origin, population genetic diversity and mating system in the contact zone between diploid and assumed autotetraploid cytotypes of Vicia cracca in Central Europe. METHODS: Four enzyme systems resolved in six putative loci were investigated in ten diploid, ten tetraploid and five mixed-ploidy populations. Genetic diversity and heterozygosity, partitioning of genetic diversity among populations and cytotypes, spatial genetic structure and fixed heterozygosity were analysed. These studies were supplemented by a pollination experiment and meiotic chromosome observation. KEY RESULTS AND CONCLUSIONS: Weak evidence of fixed heterozygosity, a low proportion of unique alleles and genetic variation between cytotypes similar to the variation among populations within cytotypes supported the autopolyploid origin of tetraploids, although no multivalent formation was observed. Tetraploids possessed more alleles than diploids and showed higher observed zygotic heterozygosity than diploids, but the observed gametic heterozygosity was similar to the value observed in diploids and smaller than expected under panmixis. Values of the inbreeding coefficient and differentiation among populations (rhoST) suggested that the breeding system in both cytotypes of V. cracca is mixed mating with prevailing outcrossing. The reduction in seed production of tetraploids after selfing was less than that in diploids. An absence of correlation between genetic and geographic distances and high differentiation among neighbouring tetraploid populations supports the secondary contact hypothesis with tetraploids of several independent origins in Central Europe. Nevertheless, the possibility of a recent in situ origin of tetraploids through a triploid bridge in some regions is also discussed. PMID- 24232384 TI - Peroxynitrite (ONOO-) is endogenously produced in arabidopsis peroxisomes and is overproduced under cadmium stress. AB - BACKGROUND AND AIMS: Peroxisomes are subcellular compartments involved in multiple cellular metabolic pathways. Peroxynitrite (ONOO(-)) is a nitric oxide derived molecule which is a nitrating species that causes nitration of proteins. This study used cell biology techniques to explore the potential presence of peroxynitrite in peroxisomes and evaluated its content under stress conditions (excess cadmium). METHODS: Peroxynitrite, nitric oxide and superoxide anion were studied using cell-permeable specific fluorescent probes by confocal laser scanning microscopy in Arabidopsis thaliana transgenic plants expressing cyan fluorescent protein through the addition of peroxisomal targeting signal 1 (PTS1), which enables peroxisomes to be visualized in vivo. Key Results When no stress was applied, peroxynitrite was clearly localized in the peroxisomes of roots and stomatal guard cells. Under cadmium (150 MUm) stress, the generation of peroxynitrite, nitric oxide and the superoxide anion (O2(.-)) increased and was localized in peroxisomes and the cytosol, participating in the generation of nitro-oxidative stress. CONCLUSIONS: The results show that peroxisomes are an endogenous source of peroxynitrite, which is over-produced under cadmium stress, suggesting that the metabolism of reactive nitrogen species in peroxisomes could participate in the mechanism of the response to this heavy metal. PMID- 24232385 TI - Molecular characterization of oxidative stress-inducible LipD of Mycobacterium tuberculosis H37Rv. AB - The Mycobacterium tuberculosis has developed intricate strategies to evade the killing of microorganism and support its survival in phagocytes. The genome sequence of bacterium revealed the presence of several genes for lypolytic enzymes. Rv1923 gene, a member of Lip family in M. tuberculosis demonstrated the least sequence similarity with its counterpart in non-pathogenic strain M. smegmatis. The expression of Rv1923 gene (LipD) was not observed in in vitro growing cultures of M. tuberculosis H37Ra while an upregulation of transcription of Rv1923 gene was noticed in oxidative conditions. For detailed characterization of LipD enzyme the Rv1923 gene was cloned in pQE30-UA vector and expressed in E. coli M15 cells. LipD was purified from inclusion bodies and refolded with nearly 40 % protein yield. The specific activity of enzyme was calculated to be 16 U/mg with pNP-palmitate as a preferred substrate. Kinetic analysis showed K(m) 0.645 mM and V(max) 24.75 U/ml with pNP-palmitate. Ser-102, Asp-342, and His-369, predicted as the members of the catalytic triad, were confirmed by mutagenesis. Mutagenesis studies revealed that catalytic serine residues located in beta lactamase motifs (S-X-X-K) were responsible for lipolytic activity. Secondary structure analysis by CD spectroscopy demonstrated the presence of alpha helices and beta sheets in the canonical structure of LipD. The enzyme was stable up to 50 degrees C and was active even at pH 6.0. The expression of enzyme under stress conditions and its activity and stability at high temperature and low pH suggested the possible role of LipD in the survival of mycobacterium in macrophage compartment. PMID- 24232387 TI - Asymmetric hybridization between cytoplasmic male-sterile (CMS) and fertile rice (Oryza safiva L.) protoplasts. AB - (60)Co-irradiated protoplasts of the cytoplasmic male-sterile line A-58 CMS (Oryza saliva L.) were electrofused with iodoacetamide (IOA)-treated protoplasts of the fertile (normal) rice cultivar 'Fujiminori'. Seven of the colonies that formed were identified as cytoplasmic hybrids (cybrids): they all had the peroxidase isozymes of the fertile 'Fujiminori' parent, but contained four plasmid-like DNAs (Bl, B2, B3 and B4) from the sterile A-58 CMS parent in their mitochondrial genomes. In addition, digestion of cybrid mtDNA gave a set of restriction fragments that differed from those of the parents. PMID- 24232386 TI - Bilateral iliopsoas hematoma: Case report and literature review. AB - BACKGROUND: Clinically significant spontaneous bilateral iliopsoas hematoma is a rare complication of anticoagulation therapy. Definitive treatment of spontaneous iliopsoas hematomas is not well-established and varies between observation and surgical intervention. The intramuscular hematoma causes severe pain, muscle dysfunction, and occasionally nerve palsy with the femoral nerve most commonly affected. Most patients are neurologically normal but when a significant neurological deficit is associated with iliopsoas hematoma, optimal treatment recommendations vary. We report a case of spontaneous bilateral iliopsoas hematomas causing significant bilateral femoral nerve dysfunction. CASE DESCRIPTION: The authors present the case of a 63-year-old female who developed bilateral femoral nerve palsy due to anticoagulation bleeding complication. Magnetic resonance imaging demonstrated large bilateral intramuscular psoas hematomas causing femoral nerve compression. Surgical evacuation and decompression of the femoral nerves was performed with rapid neurological improvement. CONCLUSION: Management recommendations depend on the volume and cause of the hematoma, timing of diagnosis, and the degree of neurological impairment. A conservative approach with bed rest and correction of bleeding abnormalities to allow the hematoma to spontaneously resorb has been utilized for patients with small hematomas and little to no neurological symptoms. In contrast, more aggressive recommendations have been made for patients with large hematomas, severe motor function deficits, or hemodynamic instability. PMID- 24232388 TI - Distribution of mitochondrial plasmid-like DNA in cultivated rice (Oryza sativa L.) and its relationship with varietal groups. AB - Mitochondrial (mt) plasmid-like DNA was found in most of more than 100 rice cultivars (Oryza sativa L.) by the use of 0.7% agarose gel electrophoresis (AGE). The DNA varied in molecular weight and number. By electron microscopy, small circular DNAs of different sizes could be detected in addition to the DNAs of high molecular weight, even in cultivars in which mt plasmid-like DNA was not detected by AGE. The detection of the mt plasmid-like DNAs by AGE did not depend on their presence or absence, but on their high stoichiometry. The relationship between cytoplasms with mt plasmid-like DNAs and varietal (for example, Indica rice) groups was close. The geographical distribution of cytoplasms is discussed. PMID- 24232389 TI - Molecular mapping of rice chromosomes. AB - We report the construction of an RFLP genetic map of rice (Oryza sativa) chromosomes. The map is comprised of 135 loci corresponding to clones selected from a PstI genomic library. This molecular map covers 1,389 cM of the rice genome and exceeds the current classical maps by more than 20%. The map was generated from F2 segregation data (50 individuals) from a cross between an indica and javanica rice cultivar. Primary trisomics were used to assign linkage groups to each of the 12 rice chromosomes. Seventy-eight percent of the clones assayed revealed RFLPs between the two parental cultivars, indicating that rice contains a significant amount of RFLP variation. Strong correlations between size of hybridizing restriction fragments and level of polymorphism indicate that a significant proportion of the RFLPs in rice are generated by insertions/delections. This conclusion is supported by the occurrence of null alleles for some clones (presumably created by insertion or deletion events). One clone, RG229, hybridized to sequences in both the indica and javanica genomes, which have apparently transposed since the divergence of the two cultivars from their last common ancestor, providing evidence for sequence movement in rice. As a by product of this mapping project, we have discovered that rice DNA is less C methylated than tomato or maize DNA. Our results also suggest the notion that a large fraction of the rice genome (approximately 50%) is single copy. PMID- 24232390 TI - A note on the effect of variation of lactation length on the efficiency of tropical cattle selection for milk yield. AB - The effects of procedures generally used to reduce variation of lactation length on the efficiency of selection for milk yield are examined applying existing theory to a set of average literature estimates of heritabilities and correlations between lactation yield and length. Adjustment of milk yield for lactation length should be expected to remove more genetic than phenotypic variation, thus reducing selection efficiency in relation to unadjusted yield. Selecting individuals on an optimum index of lactation yield and length would be more efficient for improving yield than selecting on yield alone, while both criteria would have practically the same efficiency for selection on progeny test. This result could be applied to reduce milk recording frequency without losing selection accuracy. Culling on lactation length before selecting on yield would have little effect on individual selection efficiency. However, excluding short lactation records should be expected to reduce both selection accuracy of the progeny test and genetic variation in yield. PMID- 24232391 TI - Efficient regeneration of transgenic plants from rice protoplasts and correctly regulated expression of the foreign gene in the plants. AB - Rice is one of the most important crops in the world with 35% of the total population (over two billion people) depending on it as their source of food. It is therefore essential to develop efficient methods for the transformation and regeneration of rice plants in order to delineate the exact regulatory sequences responsible for gene expression and to transfer beneficial genes into this plant. Here, for the first time, we present definitive evidence for the regeneration of a large number of transgenic rice plants after introduction of the bacterial beta glucuronidase gene into rice protoplasts. The presence of integrated copies of this gene was detected in the genome of transgenic plants by DNA hybridization analysis. Furthermore, under the control of regulatory regions from a maize alcohol dehydrogenase sequence, beta-glucuronidase gene expression was detected in the roots of transgenic plants. This expression was stimulated up to six fold under anaerobic conditions. PMID- 24232392 TI - Classifying seedlots of Picea sitchensis and P. glauca in zones of introgression using restriction analysis of chloroplast DNA. AB - Chloroplast DNA (cpDNA) restriction analysis was used to classify five reforestation seedlots as to species. The material included two Sitka spruce (Picea sitchensis (Bong.) Carr.), one white spruce (P. glauca (Moench) Voss) from interior British Columbia, and two putative hybrid seedlots from the coast interior introgression zone in British Columbia. The cpDNA patterns generated by Bam-HI and Bc1-I from individual trees of Sitka spruce, white spruce, western white spruce (P. glauca var. albertiana (S. Brown)), and Engelmann spruce (P. engelmanni (Parry)) were species-specific. They were used as reference patterns for comparisons. In addition, two controlled crosses between white and Sitka spruce were analyzed to demonstrate the paternal inheritance of cpDNA in spruces. The cpDNA restriction patterns for the five seedlots were obtained from composite samples of seedlings from each lot and compared to the typical cpDNA patterns of each species. Restriction patterns for the two Sitka spruce seedlots agreed with those from the Sitka spruce tree, while patterns for the white spruce seedlots from British Columbia agreed with those from the white spruce tree, lacking evidence of any Engelmann spruce component in the sample. On the other hand, one putative hybrid seedlot showed cpDNA patterns similar to white spruce while the other showed fragments unique to both Sitka and white spruce, indicating that this was a hybrid seedlot. The analysis of cpDNA restriction polymorphism has proven to be an effective tool for classifying seedlots in regions of introgression. To our knowledge, these results provide the first demonstration of the use of cpDNA analysis for solving practical forestry problems. PMID- 24232393 TI - Synthesis of Brassica carinata from Brassica nigra x Brassica oleracea hybrids obtained by ovary culture. AB - Brassica carinata was synthesized by hybridization between its diploid progenitor species B. nigra and B. oleracea followed by chromosome doubling. Up to 40 times more hybrids were obtained, using ovary culture than with conventional hand pollination. Two hybrids from the cross B. nigra x B. oleracea var 'alboglabra' were raised to maturity. High chromosome pairing was observed in both the hybrids and the amphidiploid. A range of variability for desirable characters is reported in the synthesized amphidiploids. PMID- 24232394 TI - Parametric relationships between genotype x environment interaction and genetic correlation when two environments are involved. AB - Parametric relationships between the genotype x environment interaction and the genetic correlation of the same attribute measured in two different environments are derived. It is shown that the criticism by Fernando et al. (1984) of Yamada's method (1962) in the case of unbalanced data is irrelevant. PMID- 24232395 TI - Transfer of the CMS trait in Daucus carota L. by donor-recipient protoplast fusion. AB - X-irradiated protoplasts of Daucus carota L., 28A1, carrying cytoplasmic male sterile (CMS) cytoplasm and iodoacetamide-treated protoplasts of a fertile carrot cultivar, 'K5', were fused with polyethylene glycol (PEG), and 73 plants were regenerated. Twenty-six randomly chosen regenerated plants had non-parental mitochondrial DNA (mtDNA) as revealed by XbaI restriction fragment patterns, and all of the plants investigated had diploid chromosome numbers. Of the 11 cybrid plants that showed mtDNA fragment patterns clearly different from those of the parents, 10 plants showed male sterility with brown or red anthers, and one plant possessed partially sterile yellow anthers. The mtDNA fragment patterns of the ten cybrid plants with male sterile flowers resembled that of a CMS parent, 28A1; and four fragments were identified that were common between the sterile cybrid plants and 28A1, but absent from the partially sterile cybrid plants and a fertile cultivar, 'K5'. The results indicated that the CMS trait of the donor was efficiently transferred into the cybrid plants by donor-recipient protoplast fusion. PMID- 24232396 TI - Selection for mating propensity in irradiated populations of the cotton boll weevil. AB - Twelve generations of family selection for 10-day post-irradiation male mating propensity resulted in significant divergence between the selected and unselected control populations. Much of this divergence was the result of a decline in the control population which was believed to have been a function of both inbreeding and environmental effects. Significant correlated responses as measured by differences in the two populations for linear time trends of performance on generations of selection were observed for 10-day post-irradiation survival, percent survivors mating at 10 days, and 7-day egg production of unirradiated females. PMID- 24232397 TI - Selection of peach cells for insensitivity to culture filtrates of Xanthomonas campestris pv. pruni and regeneration of resistant plants. AB - Individual callus cultures were initiated from 400 immature embryos of bacterial leaf spot-susceptible 'Sunhigh' peach. Each was subjected to several selection cycles of a toxic culture filtrate produced by Xanthomonas campestris pv. pruni, the causal agent of leaf spot of peach. Progressively higher concentrations of the filtrate were used in each cycle. Two calli survived, and two plants were regenerated from each of the surviving calli. Each of the four clones was propagated in vitro and tested for whole plant resistance to X. c. pv. pruni. Results from bioassays on greenhouse-grown plants indicated that two out of the four selected clones were significantly more resistant to X. c. pv. pruni than the parental cv 'Sunhigh'. In addition, one clone was significantly more resistant than the moderately resistant cv 'Redhaven'. PMID- 24232398 TI - Computer simulation of genetic control. Comparison of sterile males and field female killing systems. AB - A computer program, GENCON, designed to simulate genetic control using field female killing systems, is described. These systems incorporate sex-linked translocations and conditional lethal mutations. Genetic death in field populations is caused by semisterility of the translocation and by homozygosis of the mutations in females and non-translocation males of field origin. Simulations using the program compare the effectiveness, in populations regulated by density, of genetic control using this type of system with control using sterile-male release. At high release rates, sterile males cause more rapid suppression and earlier eradication than sex-linked translocation strains. However, if releases are interrupted before eradication, the rate of recovery of density-dependent populations is more rapid following sterile-male release than following suppression with translocation strains. In such populations, the cumulative population suppression (number of individuals killed) is greater with translocation-strain release than with sterile-male release. At low release rates, sex-linked translocation strains can be much more effective at suppressing and eradicating density-dependent populations than sterile males. In continental Australia, eradication of the sheep blowfly Lucilia cuprina is probably not practicable. A suppression campaign using sex-linked translocation strains could yield a higher benefit to cost ratio than one using sterile males. PMID- 24232399 TI - Field assessment of dihaploid Solatium tuberosum and S. brevidens somatic hybrids. AB - Following both chemical and electrical fusion of protoplasts of a dihaploid line of potato (Solanum tuberosum), (PDH40), with those of the wild species, Solanum brevidens, 11 and 40 somatic hybrid plants, respectively were obtained. Fifteen of these somatic hybrid genotypes and the two parents were studied further in a small field trial to assess field performance and phenotypic variability. In the UK, somatic hybrid plants are classified as genetically engineered organisms, and the UK Advisory Committee on Genetic Manipulation have imposed various restrictions on field experiments. Examination of the somatic hybrids in the field showed extensive phenotypic variability, and no two genotypes were identical. Some of the variation reflected changes in chromosome numbers, but other factors were also involved. Half the somatic hybrid genotypes produced tubers in the field, although the tubers were smaller and differed morphologically from those of PDH40. The results of the study suggest that the extent of somaclonal variation manifested in somatic hybrids is greater than that found in protoplast-derived plants of potato. The implications of this observation and the current regulations concerning field experiments of somatic hybrid plants in the UK are discussed. PMID- 24232400 TI - Plant regeneration from protoplasts of indica rice: genotypic differences in culture response. AB - Fourteen varieties of indica rice (Oryza saliva L.) were examined for their capacity for plant regeneration from protoplasts using the nurse culture methods developed for japonica rice. Calli induced from germinating seeds were grouped into two types: type I, white and compact; type II, yellow and friable. In four varieties producing type II callus, colony formation (2%-4.5%) and plant regeneration (2%-35%) were observed. The inability to develop suspension cultures was a major obstacle in regenerating plants from protoplasts of the remaining rice varieties studied. PMID- 24232401 TI - Increasing the transmission rate of the extra chromosome in a trisomic Nicotiana sylvestris line by modifying the means of pollination. AB - Trisomies of primary trisomic line B220 of Nicotiana sylvestris, which contain an extra chromosome shown to be a satellite chromosome, can be readily identified by their larger flower and leaf sizes. In seed-propagated species, the low transmission of the extra chromosome has prevented such plants from becoming agriculturally useful cultivars. In line B220, the transfer of the extra chromosome in 2n*2n+1 crosses was very low (13.5%), although n and n + 1 pollen grains were produced in equal quantities, as was confirmed by anther culture. This was due to the delayed development of n + 1 pollen grains, which are not at full maturity at the time of an thesis. The transfer of the extra chromosome in 2n*2n+1 crosses was increased by a 1 day delay in pollination and also by pollination of small pollen grains selected through nylon meshes. The delayed pollination increased the frequency of trisomics by 9%, whereas pollen selected by using 30 and 25 MUn nylon meshes induced an extremely high transfer of the extra chromosome, namely 51.9% and 70.4%, respectively. The observed frequencies of trisomics and tetrasomics in artificial selfing of 2n+1 plants with selected small pollen grains were lower than those expected from the data of reciprocal crosses between 2n and 2n+1 plants. This discrepancy seems to indicate a disadvantage of the n+1 pollen in fertilization due to the longer style of the trisomics relative to that of the diploids. PMID- 24232402 TI - Elimination and duplication of particular Hordeum vulgare chromosomes in aneuploid interspecific Hordeum hybrids. AB - Seeds formed in crosses Hordeum lechleri (6x) x H. vulgare (2x and 4x), H. arizonicum (6x) x H. v. (2x), H. parodii (6x) x H. v. (2x), and H. tetraploidum (4x) x H. v. (2x) produced plants at high or rather high frequencies through embryo rescue. Giemsa C-banding patterns were used to analyze chromosomal constitutions and chromosomal locations on the methaphase plate. Among 100 plants obtained from H. vulgare (2x) crosses, 32 plants were aneuploid with 2n=29 (1), 28 (3), 27 (13), 26 (5), 25 (4), 24 (4), or 22 (2); 50 were euploid (12 analyzed), and 18 were polyhaploid (5 analyzed). Four plants had two sectors differing in chromosome number. Two of four hybrids with H. vulgare (4x) were euploid and two were aneuploid. Parental genomes were concentrically arranged with that of H. vulgare always found closest to the metaphase centre. Many plants showed a certain level of intraplant variation in chromosome numbers. Except for one H. vulgare (4x) hybrids, this variation was restricted to peripherally located non-H. vulgare genomes. This may reflect a less firm attachment of the chromosomes from these genomes to the spindle. Interplant variation in chromosome numbers was due to the permanent elimination or, far less common, duplication of the centrally located H. vulgare chromosomes in all 34 aneuploids, and in a few also to loss/gain of non-H, vulgare chromosomes. This selective elimination of chromosomes of the centrally located genome contrasts conditions found in diploid interspecific hybrids, which eliminate the peripherally located genome. The difference is attributed to changed "genomic ratios'. Derivatives of various H. vulgare lines were differently distributed among euploid hybrids, aneuploids, and polyhaploids. Chromosomal constitutions of hypoploid hybrids revealed a preferential elimination of H. vulgare chromosomes 1, 5, 6, and 7, but did not support the idea that H. vulgare chromosomes should be lost in a specific order. H. vulgare SAT-chromosomes 6 and 7 showed nucleolar dominance. Aneuploidy is ascribed to the same chromosome elimination mechanism that produces haploids in cross-combinations with H. vulgare (2x). The findings have implications for the utilization of interspecific Hordeum hybrids. PMID- 24232403 TI - Reproductive fitness and artificial selection in animal breeding: culling on fitness prevents a decline in reproductive fitness in lines of Drosophila melanogaster selected for increased inebriation time. AB - The maintenance of reproductive fitness in lines subjected to artificial selection is one of the major problems in animal breeding. The decline in reproductive performance has neither been predictable from heritabilities and genetic correlations, nor have conventional selection indices been adequate to avoid the problem. Gowe (1983) has suggested that the heritabilities of reproductive traits are non-linear, with heritabilities being higher on the lower fitness side. Consequently, he has predicted that culling on reproductive fitness in artificial selection lines will be effective in preventing the usual declines in fitness. An experimental evaluation of Gowe's prediction has been carried out by comparing fitnesses of replicated lines of three treatments: selection for increased inebriation time without culling on fitness (HO), selection for inebriation time with culling of 20% (4/20) of selected females on reproductive fitness (HS), and unselected controls (C). Response to selection for inebriation time in the two selection treatments was similar. After 25 generations, the competitive index, a measure of reproductive fitness, was significantly lower in the HO treatment than the HS treatment, while the HS treatment did not differ from the control lines or the base population. These results demonstrate for the first time that culling on reproductive fitness in selection lines can be used to prevent the usual decline in reproductive performance. PMID- 24232404 TI - Intergeneric somatic hybrid production through protoplast fusion between Brassica juncea and Diplotaxis muralis. AB - The need to transfer genetic traits from Diplotaxis muralis (2n=42) to Brassica juncea (2n=36), a major oil seed crop of the tropical world, was realised. Since the two plant types are sexually incompatible, attempts were made to evolve parasexual hybrids as the result of protoplast fusion. Protoplasts of hypocotyl derived calli of two cultivars of B. juncea were fused with normal and gamma irradiated mesophyll protoplasts of Diplotaxis muralis. Regeneration of 110 plants from the fused products was successfully achieved. Upon analysis of some of them, we realised that true somatic hybrids and partial somatic hybrids had been generated. Thus the primary goal of evolving intergeneric hybridisation products between these two plant types was fulfilled. PMID- 24232405 TI - Genetics of Brazil nut (Bertholletia excelsa Humb. & Bonpl.: Lecythidaceae) : 1. Genetic variation in natural populations. AB - We provide an estimate of genetic variation within and between two populations of Bertholletia excelsa (Brazil nut), a large canopy tree found in the rain forests of South America. Average heterozygosity is 0.190, and 54.3% of the sampled loci are polymorphic. The population structure deviates significantly from Hardy Weinberg expectations for Fest2 and Pgm2 (F =0.405 and 0.443, respectively) in one population, and highly significantly (F=-0.341) for Gdh in the other population. Although allele frequencies of the two populations differ significantly for Aat2, Est5, Mdh1, and Mdh2B, Nei's coefficient of gene differentiation (Gst) indicates that the between-population component (Dst) of genic diversity represents only 3.75% of the size of the within-population component (Hs). The implications of these findings in terms of conservation genetics are that much of the genetic diversity of this species may be preserved within one or a few populations. However, such populations must be very large because it appears that the large amount of genetic variation in Brazil nut populations is maintained by extensive gene flow and bonds of mating over a large area. The genetic architecture of Bertholletia excelsa is similar to that expected for an extensively diploidized paleopolyploid species. PMID- 24232406 TI - Genetics of Brazil nut (Bertholletia excelsa Humb. & Bonpl.: Lecythidaceae) : 2. Mating system. AB - Here we report the results of a mating system analysis of an Amazonian population of Bertholletia excelsa, a tropical rain forest canopy tree species. Using progeny data from 29 seed parents, two highly polymorphic isozymes were analyzed to derive single locus and multilocus estimates of outcrossing, based on a mixed mating model. The two single locus estimates were very similar, and both were somewhat smaller than the multilocus estimate, indicating the possibility that the populations are genetically structured. The multilocus outcrossing estimate (tm=0.85+/-0.03) reveals that outcrossing is prevalent, but that a significantly low level of inbreeding may be occurring. The high outcrossing rate indicates that even though dispersion of individuals is very low within populations of this tropical rain forest tree, pollen dispersal mechanisms appear to be adequate to enable crosses with a relatively large number of potential mates. PMID- 24232407 TI - Chromosomal location by F1 monosomic analysis of endosperm proteins in bread wheat : 2. Two-dimensional fractionation of gliadins. AB - The gliadin components from four bread wheat cultivars: Chinese Spring, Capelle Desprez, Holdfast and Pane-247 and their monosomic F1s for the chromosomes of homoeologous groups 1 and 6 have been analyzed by two-dimensional (2-pH) polyacrylamide gel electrophoresis. Chromosomal location of gliadin genes and the allelic differences were well established by analyzing the different F1 monosomic hybrids, electrophoretical patterns and differences in relative staining intensity. A new gliadin encoded by a gene located on chromosome 6B in Chinese Spring is described. The two-dimensional patterns of gliadin in the other three varieties and the chromosomal location of their genes are reported for the first time. Relationships between gliadins in the two-dimensional patterns and the traditional system for their nomenclature are discussed. PMID- 24232408 TI - Flowering and branching in Lathyrus odoratus L.: loci sp and b. AB - A second flowering gene, Sp, which influences sensitivity to photoperiod, is identified in the sweet pea, Lathyrus odoratus L. Genes Sp and Dn (h) act in a complementary manner to confer the summer-flowering phenotype and a near obligate long day requirement for flowering in the unvernalized state. Mutations sp and Dn (i) each diminish the response to photoperiod, and genotypes sp Dn (h) and Sp Dn (i) confer a spring-flowering phenotype. Response to photoperiod is further reduced in genotype sp Dn (i), which flowers only marginally later than the day neutral or winter-flowering phenotype characterized by genotypes Sp dn and sp dn (gene dn is epistatic to the gene pair Sp/sp). Like Dn (i), gene sp reduces basal branching, while a branching gene, here resymbolized b, is shown to delay flowering in certain circumstances. Gene dn largely prevents basal branching in either b or B plants, but dn b plants do produce lateral shoots from the upper nodes, leading to a novel phenotype. The implications of the interactions between genes sp, Dn (i), dn and b are discussed with respect to the control of flowering and branching. PMID- 24232409 TI - The meaning of genetic variation within and between subpopulations. AB - Argumentation is presented which indicates that the additive decomposition of the total genetic variation of a population into variation within and between (among) its subpopulations suffers from conceptual inconsistency. While the measurement of variation between subpopulations can be shown to be identical to the measurement of subpopulation differentiation, the notion of variation within subpopulations, when viewed as a single measurement, cannot be derived as an independent and cogent concept. Rather, it appears to be merely technically defined as the arithmetic difference between the total variation and the variation between subpopulations, and this difference happens to be non-negative for concave measures of variation such as the (statistical) variance or certain measures of genetic diversity. In order to overcome the conceptual inconsistency, "variation between subpopulations" could be regarded as subpopulation differentiation and the notion of "variation within subpopulations" could be replaced by measurements of the degree to which the variation in the total population is represented within the subpopulations. A complementary situation with respect to total variation is thus realized once more, and appropriate measures can be directly derived from existing ones. PMID- 24232411 TI - Economic analyses of genetic tests in personalized medicine: clinical utility first, then cost utility. PMID- 24232410 TI - The claudin family of proteins in human malignancy: a clinical perspective. AB - Tight junctions, or zonula occludens, are the most apical component of the junctional complex and provide one form of cell-cell adhesion in epithelial and endothelial cells. Nearly 90% of malignant tumors are derived from the epithelium. Loss of cell-cell adhesion is one of the steps in the progression of cancer to metastasis. At least three main tight junction family proteins have been discovered: occludin, claudin, and junctional adhesion molecule (JAM). Claudins are the most important structural and functional components of tight junction integral membrane proteins, with at least 24 members in mammals. They are crucial for the paracellular flux of ions and small molecules. Overexpression or downregulation of claudins is frequently observed in epithelial-derived cancers. However, molecular mechanisms by which claudins affect tumorigenesis remain largely unknown. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies, including pancreatic, colonic, lung, ovarian, thyroid, prostate, esophageal, and breast cancers. In this review, we will give the readers an overall picture of the changes in claudin expression observed in various cancers and their mechanisms of regulation. Downregulation of claudins contributes to epithelial transformation by increasing the paracellular permeability of nutrients and growth factors to cancerous cells. In the cases of upregulation of claudin expression, the barrier function of the cancerous epithelia changes, as they often display a disorganized arrangement of tight junction strands with increased permeability to paracellular markers. Finally, we will summarize the literature suggesting that claudins may become useful biomarkers for cancer detection and diagnosis as well as possible therapeutic targets for cancer treatment. PMID- 24232412 TI - Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder. AB - PURPOSE: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and cafe au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1. METHODS: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Campanacci syndrome or Jaffe Campanacci syndrome-related features. We also performed somatic NF1 mutation testing on nonossifying fibromas and giant cell lesions. RESULTS: Pathogenic germline NF1 mutations were identified in 13 of 14 patients with multiple cafe-au lait macules and multiple nonossifying fibromas or giant cell lesions ("classical" Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institutes of Health diagnostic criteria for neurofibromatosis type 1. Somatic NF1 mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1 negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions. CONCLUSION: In this study, the majority of patients with cafe-au lait macules and nonossifying fibromas or giant cell lesions harbored a pathogenic germline NF1 mutation, suggesting that many Jaffe-Campanacci syndrome cases may actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NF1 in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1 associated tumors. PMID- 24232413 TI - The economic value of personalized medicine tests: what we know and what we need to know. AB - PURPOSE: There is uncertainty about when personalized medicine tests provide economic value. We assessed evidence on the economic value of personalized medicine tests and gaps in the evidence base. METHODS: We created a unique evidence base by linking data on published cost-utility analyses from the Tufts Cost-Effectiveness Analysis Registry with data measuring test characteristics and reflecting where value analyses may be most needed: (i) tests currently available or in advanced development, (ii) tests for drugs with Food and Drug Administration labels with genetic information, (iii) tests with demonstrated or likely clinical utility, (iv) tests for conditions with high mortality, and (v) tests for conditions with high expenditures. RESULTS: We identified 59 cost utility analyses studies that examined personalized medicine tests (1998-2011). A majority (72%) of the cost/quality-adjusted life year ratios indicate that testing provides better health although at higher cost, with almost half of the ratios falling below $50,000 per quality-adjusted life year gained. One-fifth of the results indicate that tests may save money. CONCLUSION: Many personalized medicine tests have been found to be relatively cost-effective, although fewer have been found to be cost saving, and many available or emerging medicine tests have not been evaluated. More evidence on value will be needed to inform decision making and assessment of genomic priorities. PMID- 24232414 TI - Effect of preoperative carbohydrate loading on the management of blood glucose and body temperature. PMID- 24232415 TI - SO2 and NO2 effects on microbial activity in an acid forest soil. AB - The rate of glucose decomposition and the pH fell in a forest soil (initial pH 4.06) exposed to 1.0 ppm SO2. No such effect was noted if the soil was exposed to 1.0 ppm nitrogen dioxide (NO2). Nitrite but not bisulfite (5MUg N or S/g of soil) inhibited O2 consumption and CO2 evolution in the glucose-amended forest soil, and nitrite and bisulfite acted synergistically in inhibiting these processes. Iron and manganese were solubilized when the soil was exposed to 10 ppm SO2, but NO2 caused no such change. PMID- 24232416 TI - Bacterial ecology of an old-growth douglas fir canopy. AB - Microbial populations associated with the major substrates of the canopy of a single 70 m old-growth Douglas fir were studied to determine potential activities. Seasonal samples from bark, foliage, epiphytic moss, lichens, and litter accumulations were collected to: (a) obtain population data, (b) isolate the major groups of microorganisms present, (c) measure enzymatic activities associated with cellulose and xylan degradation, and (d) examine the potential for nitrogen fixation. We tested 562 bacterial isolates for utilization of 25 compounds associated with the canopy substrates, and for activities in nitrogen and sulfur cycle transformations. Total bacterial populations, reflecting seasonal temperature and moisture conditions, were lowest on bark and foliage [21 266*10(3) colony-forming units (CFU/g)] and highest on moss and lodged litter (19 610*10(5) CFU/g). Lichens contained intermediate numbers of bacteria (3.3 270*10(5) CFU/g). The majority of the bacteria were classified as species ofArthrobacter, Bacillus, Flavobacterium, andXanthomonas. Isolates ofAlcaligenes (Achromobacter), Aeromonas, Chromobacterium, Micrococcus, andPseudomonas were less common. No measurable rates of nitrogen fixation attributable to free-living bacteria were detected by acetylene reduction. Eleven species in six genera of lichens containing a blue-green algal phycobiont showed positive acetylene reduction. One species,Lobaria oregana, accounted for 51% of the total lichen biomass of the canopy. Cellulase and xylanase activity was routinely detected in moss and litter samples, and less frequently in lichens. There was a strong correlation between the two activities for moss (r=0.94) and litter (r=0.81). PMID- 24232417 TI - A comparison of oxygen, nitrate, and sulfate respiration in coastal marine sediments. AB - Aerobic respiration with oxygen and anaerobic respiration with nitrate (denitrification) and sulfate (sulfate reduction) were measured during winter and summer in two coastal marine sediments (Denmark). Both aerobic respiration and denitrification took place in the oxidized surface layer, whereas sulfate reduction was most significant in the deeper, reduced sediment. The low availability of nitrate apparently limited the activity of denitrification during summer to less than 0.2 mmoles NO 3 (-) m(-2) day(-1), whereas activities of 1.0 3.0 mmoles NO 3 (-) m(-2) day(-1) were measured during winter. Sulfate reduction, on the contrary, increased from 2.6-7.6 mmoles SO 4 (2-) m(-2) day(-1) during winter to 9.8-15.1 mmoles SO 4 (2-) m(-2) day(-1) during summer. The aerobic respiration was high during summer, 135-140 mmoles O2 m(-2) day(-1), as compared to estimated winter activities of about 30 mmoles O2 m(-2) day(-1). The little importance of denitrification relative to aerobic respiration and sulfate reduction is discussed in relation to the availability and distribution of oxygen, nitrate, and sulfate in the sediments and to the detritus mineralization. PMID- 24232418 TI - Occurrence ofThioploca in Lake Constance and Lower Saxony, Germany. AB - Thioploca had been encountered in several locations in Central Europe. Five of these were revisited to find out ifT. schmidlei andT. ingrica were still present in these locations. Of the three locations in Lake Constance with abundant populations, one (Staad) contained a sparse population of small specimens ofT. ingrica only; from the others (Ermatingen and Mainau) neither species was recovered. In Lower Saxony two spots reportedly containedT. ingrica. The first of these (Buckeburg) has been destroyed by human stream improvement. The description of the other (Bad Nenndorf) was insufficient for relocation. During the search a new location containingT. ingrica was discovered, Crater Spring, across highway B65 from Bad Nenndorf. PMID- 24232419 TI - An indirect fluorescent antibody staining technique for determining population levels ofThiobacillus ferrooxidans in acid mine drainage waters. AB - Thiobacillus ferrooxidans is believed to be responsible for the oxidation of ferrous ion at low pH, the rate-limiting step in the oxidation of pyrite ores and subsequent formation of acid mine drainage (AMD). It has been suggested that efforts to control this environmental problem include procedures that would inhibit this bacterium. At present, a most probable number (MPN) procedure requiring a minimum of 10 days is used to enumerate this microorganism in natural waters. If control of AMD through inhibition ofT. ferrooxidans is to be feasible, it will be necessary to develop a more rapid method to determine population levels to facilitate application of control measures.An indirect fluorescent antibody (FA) staining technique was developed for this purpose which provided reliable estimates within a few hours. Artificial samples containing approximated numbers ofT. ferrooxidans were analyzed using the FA and MPN procedures, and the FA technique more closely approximated expected numbers of cells. The MPN method was excessively conservative, detecting only 3% to 21% of the cells enumerated by the FA procedure. PMID- 24232420 TI - Influence of cation content on adenosine triphosphate determinations in soil. AB - Adenosine triphosphate in soil is measured by the luciferin-luciferase bioluminescence method. Cation exchange in the ATP extraction procedure is used to reduce the content of, e.g., Fe, Al, and Cations in extracts. The efficiency of the cation exchange is determined by measuring the concentration of Fe by X ray fluorescence spectrometry. The time dependence of the light emission from the bioluminescence process is investigated, and a method for correlating the ATP content and the light emission is proposed. PMID- 24232421 TI - Inhibitory effects of copper on bacteria related to the free ion concentration. AB - Cu(2+) ion determinations were carried out in complex and in inorganic salts glycerol media, to which increasing amounts of Cu(II) had been added, with the ion-specific Cu(II)-Selectrode. Likewise, complexing capacity of bacterial suspensions was estimated by titration with CuSO4.Copper-sensitive bacteria, e.g.,Klebsiella aerogenes, were inhibited in their growth and survival in the range of 10(-8)-10(-6) M Cu(2+) ion concentrations. In copper-buffered complex media, high copper loads could be tolerated, as growth proceeded with most of the copper bound to medium components. In low-complexing mineral salts media, in which high Cu(2+) ion concentrations exist at low copper loads, there was competition of Cu(2+) for binding sites of the cells. Total allowed copper was then determined by the ratio of copper to biomass.Copper-resistant bacteria could be isolated from a stock solution of CuSO4, containing 100 ppm Cu(II). They were of thePseudomonas type and showed a much higher tolerance towards Cu(2+), up to 10(-3) M. PMID- 24232422 TI - Glutamine synthetase: activity and localization in cyanobacteria of the cycadsCycas revoluta andZamia skinneri. AB - Nitrogen-fixing cyanobacteria inhabit the zone between the inner and outer cortex of cycad coralloid roots. In the growing tip of such roots the cyanobacterial heterocyst frequency, nitrogenase activity (C2H2-reduction) and glutamine synthetase activity (both transferase and biosynthetic) were comparable to those found in freeliving cyanobacteria. The relative level of glutamine synthetase protein and its pattern of cellular/subcellular localization in heterocysts and vegetative cells were also similar to those of free-living cyanobacteria. However, there was a progressive decline in nitrogenase activity along the coralloid root with maximum reduction occurring in the regions farthest from the growing tip. A similar but less pronounced pattern was observed for glutamine synthetase activity. Distribution of glutamine synthetase protein in cyanobacteria in the first 2-3 mm of the root tip indicated a slight decrease in the heterocysts and vegetative cells. However, the overall level of cyanobacterial glutamine synthetase protein did not change because of a drastic increase in the numbers of heterocysts, which contain a proportionally higher level of glutamine synthetase than the vegetative cells. PMID- 24232423 TI - Some regulatory aspects of [(14)C]methylamine influx intoPisum sativum L. cv. Feltham First seedlings. AB - [(14)C]Methylamine influx intoPisum sativum L. cv. Feltham First seedlings showed Michaelis-Menten-type kinetics with apparentV max=49.2 MUmol.g(-1) FW.h(-1) and apparentK m=0.51 mM. The competitive interactions between ammonium and methylamine were most obvious when biphasic kinetics were assumed with saturation of the first phase at ~0.05 mM. The inhibitor constant for ammonium (K i)=0.027 mM. When [(14)C]methylamine was used in trace amounts with ammonium added as substrate, the influx of tracer showed Michaelis-Menten-type kinetics with apparentV max=3.46 MUmol.g(-1) FW.h(-1) and apparentK m=0.15 mM. The initial rate of net ammonium uptake corresponded with that found when [(14)C]methylamine was used to 'trace' ammonium influx. The latter was also stimulated by high pHo and inhibited by nitrate. Ammonium pretreatment+/-methionine sulphoximine or glutamine pretreatment of the seedlings inhibited subsequent [(14)C]methylamine influx, while methylamine or asparagine pretreatment stimulated [(14)C]methylamine influx. There was also a stimulatory effect of prior inoculation withRhizobium. The results are discussed in terms of current models for the regulation of ammonium uptake in plants. PMID- 24232424 TI - Local application of indole-3-acetic acid, by resin beads to intact growing maize roots. AB - Five types of anion-exchanger resin beads which had adsorbed indole-3-acetic acid (IAA) were tested as IAA donors. The rate of IAA-uptake by beads was a function of time and pH. The release was relatively steady during 6 h application on vertical maize roots. No IAA degradation occurred in the beads (Amberlite IRA 400 type) but 45.8% was metabolised in the roots during treatment. Beads loaded with IAA and placed on one side of the root (at 2.20+/-0.03 mm from the tip) induced a curvature towards and above the bead (23.3+/-1.1 degrees after 5.25 h application). In contrast, control beads (without IAA) did not change the axial growth rate. Applied IAA seemed to move differently from endogenous IAA. The use of resin beads loaded with IAA offers a technique to study the effects of local IAA application on intact growing roots. PMID- 24232425 TI - Carotenoid synthesis and pleiotropic effects in carotenoid-deficient seedlings of maize. AB - Plastid-envelope membranes from seedlings ofZea mays L. made carotenoid-deficient by either norflurazon treatment or mutation lack an activity permitting conversion of phytoene to beta-carotene. This activity in membrane fractions was measured by coincubation in vitro with a soluble system from spinach chloroplasts capable of converting [(14)C]isopentenyl pyrophosphate into phytoene. When grown in light, the carotenoid-deficient seedlings lack many soluble chloroplast proteins, including NADP-dependent malic enzyme (EC 1.1.1.40), pyruvate phosphate dikinase (EC 2.7.9.1), and ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39), but apparently still contain the soluble activities permitting synthesis of phytoene. PMID- 24232426 TI - Safflower microsomes catalyse oil accumulation in vitro: A model system. AB - Microsomal membrane preparations from the developing cotyledons of safflower (Carthamus tinctorius L.) seed catalyse the formation of triacylglycerol fromsn glycerol 3-phosphate and linoleoyl-CoA. Conditions of incubation were achieved in which the rate of triacylglycerol synthesis approached activities which were compatible with oil accumulation observed in vivo. Reaction mixtures which contained the microsomes took on a white soup-like appearance as triacylglycerol synthesis proceeded and sufficient oil was produced to form a white fat-pad at the surface after centrifugation. The development of the oil bodies in the microsomal membranes was studied by electron microscopy and showed that lipid droplets were formed in or on the membrane surface and were then released as apparently naked entities into the surrounding medium. The ontogeny of the oil droplet in vitro is discussed in terms of oil-body formation in vivo. PMID- 24232427 TI - Photosynthetic characteristics of mesophyll cells isolated from cladophylls ofAsparagus officinalis L. AB - Intact mesophyll cells can be rapidly isolated from the cladophylls ofAsparagus officinalis by gentle scraping with a plastic card, the yield being higher than 80% on a chlorophyll basis. The cells can be stored for at least 24h without loss of photosynthetic capacity and were found to be stable under a variety of conditions. In contrast to cell preparations from other plant species, photosynthetic activity was little affected by the presence of sorbitol as an osmoticum up to a concentration of 1.5 M. Similarly, the pH value of the medium influenced photosynthesis to only a small extent at a constant [CO2] of 200 MUM. The response of the cells' photosynthetic capacity to light, temperature and CO2 concentration was similar to those reported for isolated cells from other plant species. Isolated cells ofA. officinalis can be used under a large range of conditions which gives them a measure of flexibility not possible with most plant cells which have sharply defined optimal conditions for photosynthesis. The isolated cells have a photosynthetic capacity of 40-60% of that of the intact cladophyll. The loss of photosynthetic activity observed upon isolation could not be accounted for by breakage of the cells. Virtually all of the cells were shown to be intact on the basis of Evans Blue exclusion and more than 80% of the cells contained intact chloroplasts and vacuoles. The entire loss of photosynthetic activity could be accounted for by a decrease in sucrose synthesis rather than by an equal decrease in the synthesis in all products. A six- to seven fold increase in the level of(14)C in hexose phosphates in the isolated cells supports the notion of inhibition of the sucrose-synthesis pathway. PMID- 24232428 TI - Altered feedback sensitivity of acetohydroxyacid synthase from valine-resistant mutants of tobacco (Nicotiana tabacum L.). AB - Acetohydroxyacid synthase (EC 4.1.3.18) has been extracted from leaves of three valine-resistant (Val(r)) tobacco (Nicotiana tabacum) mutants, and compared with the enzyme from the wild-type. The enzyme from all three mutants is appreciably less sensitive to inhibition by leucine and valine than the wild-type. Two of the mutants, Val(r)-1 and Val(r)-6, have very similar enzymes, which under all conditions are inhibited by less than half that found for the wild-type. The other mutant, Val(r)-7, has an enzyme that only displays appreciably different characteristics from the wild-type at high pyruvate or inhibitor concentrations. Enzyme from Val(r)-7 also has a higher apparent Km for pyruvate, threefold greater than the value determined for the wild-type and the other mutants. The sulphonylurea herbicides strongly inhibit the enzyme from all the lines, though the concentrations required for half-maximal inhibition of enzyme from Val(r)-1 and Val(r)-6 are higher than for Val(r)-7 or the wildtype. No evidence has been found for multiple isoforms of acetohydroxyacid synthase, and it is suggested that the valine-resistance of these mutant lines is the result of two different mutations affecting a single enzyme, possibly involving different subunits. PMID- 24232429 TI - Selective expression of a probable amylase/protease inhibitor in barley aleurone cells: Comparison to the barley amylase/subtilisin inhibitor. AB - We have cloned and sequenced a 650-nucleotide cDNA from barley (Hordeum vulgare L.) aleurone layers encoding a protein that is closely related to a known alpha amylase inhibitor from Indian finger millet (Eleusine coracana Gaertn.), and that has homologies to certain plant trypsin inhibitors. mRNA for this probable amylase/protease inhibitor (PAPI) is expressed primarily in aleurone tissue during late development of the grain, as compared to that for the amylase/subtilisin inhibitor, which is expressed in endosperm during the peak of storage-protein synthesis. PAPI mRNA is present at high levels in aleurone tissue of desiccated, mature grain, and in incubated aleurone layers prepared from rehydrated mature seeds. Its expression in those layers is not affected by either abscisic acid or gibberellic acid, hormones that, respectively, increase and decrease the abundance of mRNA for the amylase/subtilisin inhibitor. PAPI mRNA is almost as abundant in gibberellic acid-treated aleurone layers as that for alpha amylase, and PAPI protein is synthesized in that tissue at levels that are comparable to alpha-amylase. PAPI protein is secreted from aleurone layers into the incubation medium. PMID- 24232430 TI - Evidence for a uridine-5'-diphosphate-glucose-protectedp-chloromercuribenzene sulfonic acid-binding site in sugarcane vacuoles. AB - The uptake of uridine-5'-diphosphate (UDP) glucose into vacuoles isolated fromSaccharum sp. cells was fully inhibited by pretreatment with 50 MUMp chloromercuribenzenesulfonic acid (PCMBS) and was not affected by N ethylmaleimide up to a concentration of 5 mM. The addition of 10 mM UDP-glucose during the pretreatment partially protected the uptake mechanism from PCMBS inhibition, while the presence of adenosine-5'-diphosphate (ADP) glucose or of various hexose-phosphates had no protective effect. Parallel experiments on the binding of [(203)Hg]PCMBS to the vacuoles showed that UDP-glucose and UDP added at 10 mM concentrations caused a 40% decrease in the binding of PCMBS while ADP glucose did not inhibit the binding. The results indicate the presence in a previously proposed group translocator of at least one site that can bind UDP glucose. This site, which is blocked by PCMBS, interacts with the nucleotide moiety of UDP-glucose. PMID- 24232431 TI - Thermodynamic analysis of nonelectrolyte sorption in plant cuticles: The effects of concentration and temperature on sorption of 4-nitrophenol. AB - The sorption of 4-nitrophenol (4-NP) in enzymatically isolated cuticles ofLycopersicon esculentum fruits andFicus elastica leaves was studied as a function of temperature and solute concentration. Plots of the concentrations of 4-NP sorbed in the cuticle versus the equilibrium concentrations in the aqueous phase gave linear isotherms at low concentrations that tended to approach plateaus at higher sorbate concentrations (>= 10 mmol.kg(-1)). At low concentrations of sorbed 4-NP, cuticles have sorptive properties similar to those of organic solvents which are able to form intermolecular hydrogen bonds, while at higher concentrations their solid nature becomes apparent. During sorption of 4-NP the cutin matrix swells and new sorption sites are successively formed. The partition coefficients of 4-NP in the system cuticle/buffer are functions of temperature and concentration. At high sorbate concentrations (approx. 1 mol.kg( 1)) they approach a value of 1. Different sorptive properties were observed for the cutin regions normally encrusted with soluble cuticular lipids (SCL) and those without SCL. Increasing temperature augmented the number of sorption sites in the cutin ofLycopersicon while no effect was observed withFicus. The changes of partial molar free energy (DeltaG (o) tr), enthalpy (DeltaH (o) tr), and entropy (DeltaS (o) tr) for the phase transfer of 4-NP also depended on sorbate concentration: DeltaH (o) tr and DeltaS (o) tr were negative and steeply decreased at high sorbate concentrations. This is due to solute-solute interactions replacing solute-cutin interactions at high concentrations resulting in solid precipitates of solute within the cutin matrix. This formation of ordered solid domaines starting from a small number of nonelectrolyte molecules interacting with the cutin is proposed as a model for the intracuticular deposition of SCL. PMID- 24232432 TI - Regulation of carbonic-anhydrase activity, inorganic-carbon uptake and photosynthetic biomass yield inChlamydomonas reinhardtii. AB - The regulation of carbonic anhydrase by environmental conditions was determined forChlamydomonas reinhardtii. The depression of carbonic anhydrase in air-grown cells was pH-dependent. Growth of cells on air at acid pH, corresponding to 10 MUm CO2 in solution, resulted in complete repression of carbonic-anhydrase activity. At pH 6.9, increasing the CO2 concentration to 0.15% (v/v) in the gas phase, corresponding to 11 MUM in solution, was sufficient to completely repress carbonic-anhydrase activity. Photosynthesis and intracellular inorganic carbon were measured in air-grown and high-CO2-grown cells using a silicone-oil centrifugation technique. With carbonic anhydrase repressed cells limited inorganic-carbon accumulation resulted from non-specific binding of CO2. With air grown cells, inorganic-carbon uptake at acid pH, i.e. 5.5, was linear up to 0.5 mM external inorganic-carbon concentration whereas at alkaline pH, i.e. 7.5, the accumulation ratio decreased with increase in external inorganic-carbon concentration. It is suggested that in air-grown cells at acid pH, CO2 is the inorganic carbon species that crosses the plasmalemma. The conversion of CO2 to HCO 3 (-) by carbonic anhydrase in the cytosol results in inorganic-carbon accumulation and maintains the diffusion gradient for carbon dioxide across the cell boundary. However, this mechanism will not account for energy-dependent accumulation of inorganic carbon when there is little difference in pH between the exterior and cytosol. PMID- 24232433 TI - The carotenoid and abscisic acid content of viviparous kernels and seedlings ofZea mays L. AB - Carotenoid and abscisic acid (ABA) levels were determined in endosperm, embryos and seedlings of wild-type and viviparous (vp) mutants ofZea mays L. Carotenoid concentrations were determined by absorption spectrometry following purification by high-performance liquid chromatography and ABA concentrations by combined gas chromatography-mass spectrometry. Lutein and zeaxanthin were the terminal carotenoids in wild-type tissue. The carotenoid profiles ofvp-1 andvp-8 tissue were similar to that of the wild type; invp-2, vp-5, vp-7 andvp-9 carotenogenesis was blocked at early stages so that xanthophylls were absent. Except forvp-1, where the ABA content was similar to the wild type, the ABA content ofvp embryos was substantially reduced, to 6-16% of the corresponding wild type. Thus, the absence of xanthophylls was associated with reduced ABA content, which was in turn correlated with vivipary. Kernels ofvp-8 had a reduced ABA content although xanthophylls were present. Seedlings of carotenoid-deficient mutants rescued from viviparous kernels contained less ABA than did wild-type seedlings grown in the same way. Furthermore, the ABA concentration of such seedlings did not increase in response to water deficit. Conversely,vp-1 seedlings contained normal levels of carotenoids and ABA. Carotenoid-deficient seedlings did not contain appreciable amounts of chlorophyll so that chloroplast development was not normal. Thus ABA-deficiency could be associated with abnormal plastid development rather than the absence of carotenoids per se. PMID- 24232434 TI - L-Phenylalanine ammonia-lyase fromPhaseolus vulgaris: Modulation of the levels of active enzyme bytrans-cinnamic acid. AB - The extractable activity ofL-phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) in cell suspension cultures of bean (Phaseolus vulgaris) is greatly induced following exposure to an elicitor preparation from the cell walls of the phytopathogenic fungusColletotrichum lindemuthianum. Following exogenous application oftrans-cinnamic acid (the product of the PAL reaction) to elicitor induced cells, the activity of the enzyme rapidly declines. Loss of enzyme activity is accompanied by inhibition of the rate of synthesis of PAL subunits, as determined by [(35)S]methionine pulse-labelling followed by specific immunoprecipitation; this is insufficient to account for the rapid loss of PAL enzyme activity. Pulse-chase and immune blotting experiments indicate that cinnamic acid does not affect the rate of degradation of enzyme subunits, but rather mediates inactivation of the enzyme. A non-dialysable factor from cinnamicacid-treated bean cells stimulates removal of PAL activity from enzyme extracts in vitro; this effect is dependent on the presence of cinnamic acid. Such loss of enzyme activity in vitro is accompanied by an apparent loss or reduction of the dehydroalanine residue of the enzyme's active site, as detected by active-site-specific tritiation, although levels of immunoprecipitable enzyme subunits do not decrease. Furthermore, cinnamic-acid-mediated loss of enzyme activity in vivo is accompanied, in pulse-chase experiments, by a greater relative loss of(35)S-labelled enzyme subunits precipitated by an immobilised active-site affinity ligand than of subunits precipitated with anti immunoglobulin G. It is therefore suggested that a possible mechanism for cinnamic-acid-mediated removal of PAL activity may involve modification of the dehydroalanine residue of the enzyme's active site. PMID- 24232435 TI - Regulation of processing of a plant glycoprotein in the Golgi complex: A comparative study usingXenopus oocytes. AB - The synthesis of phytohemagglutinin (PHA), the major seed lectin ofPhaseolus vulgaris, was investigated inXenopus oocytes injected with RNA isolated from developing bean cotyledons. As is the case for normal PHA, oocyte-synthesized PHA polypeptides were found to contain two asparagine-linked oligosaccharide chains, one of which was of the high-mannose type and the other one of the Golgi-modified type, being largely resistant to endo-beta-N-acetylglucosaminidase H digestion and containing fucose. The modified oligosaccharide chain of oocyte-synthesized PHA appeared to be much larger and more heterogeneous with respect to the modified chain normally present on PHA. When the oocytes were injected with purified mRNA for PHA, isolated by hybrid-selection using a PHA complementary-DNA clone, the results were the same as those obtained by injecting total cotyledonary RNA. On the whole, these results indicate that plant glycoproteins are directed to the Golgi complex even when synthesized in an animal cell, and that correct sorting of the oligosaccharide chains to be processed is independent of the cell-type in which protein synthesis occurs. The form of processing is however cell-type specific. PMID- 24232436 TI - Metabolism of some amino acids in relation to the photorespiratory nitrogen cycle of pea leaves. AB - (15)N-labelled (amino group) asparagine (Asn), glutamate (Glu), alanine (Ala), aspartate (Asp) and serine (Ser) were used to study the metabolic role and the participation of each compound in the photorespiratory N cycle ofPisum sativum L. leaves. Asparagine was utilised as a nitrogen source by either deamidation or transamination, Glu was converted to Gln through NH3 assimilation and was a major amino donor for transamination, and Ala was utilised by transamination to a range of amino acids. Transamination also provided a pathway for Asp utilisation, although Asp was also used as a substrate for Asn synthesis. In the photorespiratory synthesis of glycine (Gly), Ser, Ala, Glu and Asn acted as sources of amino-N, contributing, in the order given, 38, 28, 23, and 7% of the N for glycine synthesis; Asp provided less than 4% of the amino-N in glycine. Calculations based on the incorporation of(15)N into Gly indicated that about 60% (Ser), 20% (Ala), 12% (Glu) and 11% (Asn) of the N metabolised from each amino acid was utilised in the photorespiratory nitrogen cycle. PMID- 24232437 TI - Photosynthetic characteristics of detached barley leaves during greening in the presence of SAN 9785. AB - The effects of the pyridazinone compound SAN 9785 on the photosynthetic competence of leaves, on the photochemical activity of isolated thylakoids and on the formation and spectral properties of chlorophyll-protein complexes were studied during a 72-h greening period of detached etiolated leaves of barley (Hordeum vulgare L. cv. Horpacsi ketsoros). It was established that i) the photosynthetic capacity of the leaves decreased considerably (by 80 and 90%, as determined by(14)CO2 fixation and fast fluorescence induction measurements, respectively); ii) the photochemical activity of isolated thylakoids from water to potassium ferricyanide and from dichlorophenol indophenol/ascorbate to methylviologen exhibited only slight reductions when expressed on a chlorophyll basis compared with the control; iii) the slow fluorescence induction curves of the treated leaves demonstrated the presence of a peculiar fluorescence component interrupting the quenching of fluorescence at around 1 min illumination; iv) a shortage of the chlorophyll-protein complex of photosystem I (CPI) occurred with a higher content of the monomer of the light harvesting complex in the thylakoids of treated leaves; and v) the fluorescence spectrum of the CPI band present in treated leaves indicates the destruction of the structural integrity of this complex during isolation from the membrane. PMID- 24232438 TI - Metabolism and bioconversion of chromene derivatives inAgeratina adenophora (Asteraceae). AB - Seedlings ofAgeratina adenophora accumulate the chromenes demethoxyencecalin, encecalin and demethylencecalin. More than 80% of the total chromenes within the seedling are confined to the leaves where they are stored within the mesophyll. Metabolism of the chromenes during development of the seedlings was subjected to analysis by high-performance liquid chromatography. The accumulation kinetics obtained, as well as feeding experiments with non-radioactive chromenes, showed the bioconversion of these compounds to proceed from demethoxyencecalin via hydroxylation yielding demethylencecalin, followed by methylation yielding encecalin. Inhibitor studies with glyphosate indicate that the chromenes arise from precursors derived from the shikimic-acid pathway. PMID- 24232440 TI - The history of neurosurgery in Bolivia and pediatric neurosurgery in Santa Cruz de la Sierra. AB - The practice of neurosurgery in Bolivia began thousands of years ago with skull trepanation. This procedure dates from the earliest period of the Tiwanaku culture, a preInca civilization. Neurosurgical development in Bolivia has its origins in the late 19(th) century and can be divided in two stages. At the beginning, before the advent of neurosurgery as a discipline, some general surgeons performed procedures on the skull and brain. Formal neurosurgery in Bolivia was developed with the arrival of neurosurgeons trained in the United States and some countries of South America. The Bolivian Neurosurgical Society was created in 1975. Nowadays, our national society has 74 members. It is affiliated with the World Federation of Neurosurgical Societies and the Latin American Federation of Neurosurgical Societies. Presently, neurosurgery in Bolivia is similar to that seen in developed countries. In this sense, government programs should dedicate more financial support to establish specialized healthcare centers where the management of complex central nervous system lesions could be offered. In contrast, we believe that encouraging the local training of young neurosurgeons is one of the most important factors in the development of neurosurgery in Bolivia or any other country. PMID- 24232441 TI - A facile bacterial assisted electrochemical self-assembly of polypyrrole micro pillars: towards underwater low adhesive superoleophobicity. AB - By taking advantage of bacterial extracellular electron transfer behavior, a facile method was developed to fabricate oriented polypyrrole micro-pillars (PPy MP) with nanoscale surface roughness. Microbes acted as a living conductive template on which PPy was in situ polymerized. The as-prepared PPy-MP exhibit the distinctive underwater low adhesive superoleophobicity which is attributable to the unique hierarchical micro/nano-structures and the high surface energy by doping with inorganic small anions. PMID- 24232442 TI - Differential, but not opponent, effects of L -DOPA and citalopram on action learning with reward and punishment. AB - RATIONALE: Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. OBJECTIVE: To investigate the role of dopamine and serotonin in the interaction between action and valence during learning.Methods We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. RESULTS: We found that, after administration of levodopa,action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control.Citalopram had distinct effects, increasing participants'tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. CONCLUSIONS: Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning. PMID- 24232443 TI - A new view of the effect of dopamine receptor antagonism on operant performance for rewarding brain stimulation in the rat. AB - RATIONALE: Previous studies of neuroleptic challenges to intracranial self stimulation (ICSS) employed two-dimensional (2D) measurements (curve shifts). Results so obtained are ambiguous with regard to the stage of neural processing at which the drug produces its performance-altering effect. We substituted a three-dimensional (3D) method that measures reward-seeking as a function of both the strength and cost of reward. This method reveals whether changes in reward seeking are due to drug action prior to the output of the circuitry that performs spatiotemporal integration of the stimulation-induced neural activity. OBJECTIVES: The aim of this study was to obtain new information about the stage of neural processing at which pimozide acts to alter pursuit of brain stimulation reward (BSR). METHODS: Following treatment with pimozide (0.1 mg/kg) or its vehicle, the proportion of trial time allocated to working for BSR was measured as a function of pulse frequency and opportunity cost. A surface defined by Shizgal's reward-mountain model was fitted to the drug and vehicle data. RESULTS: Pimozide lowered the cost required to decrease performance for a maximal BSR to half its maximal level but did not alter the pulse-frequency required to produce a reward of half-maximal intensity. CONCLUSIONS: Like indirect dopamine agonists, pimozide does not alter the sensitivity of brain reward circuity but changes reward-system gain, subjective effort costs, and/or the value of activities that compete with ICSS. The 3D method is more sensitive and informative than the 2D methods employed previously. PMID- 24232444 TI - Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development. AB - RATIONALE: Fragile X syndrome (FXS) is considered the leading inherited cause of intellectual disability and autism. In FXS, the fragile X mental retardation 1 (FMR1) gene is silenced and the fragile X mental retardation protein (FMRP) is not expressed, resulting in the characteristic features of the syndrome. Despite recent advances in understanding the pathophysiology of FXS, there is still no cure for this condition; current treatment is symptomatic. Preclinical research is essential in the development of potential therapeutic agents. OBJECTIVES: This review provides an overview of the preclinical evidence supporting metabotropic glutamate receptor 5 (mGluR5) antagonists as therapeutic agents for FXS. RESULTS: According to the mGluR theory of FXS, the absence of FMRP leads to enhanced glutamatergic signaling via mGluR5, which leads to increased protein synthesis and defects in synaptic plasticity including enhanced long-term depression. As such, efforts to develop agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. Animal models, particularly the Fmr1 knockout mouse model, have become invaluable in exploring therapeutic approaches on an electrophysiological, behavioral, biochemical, and neuroanatomical level. Two direct approaches are currently being investigated for FXS treatment: reactivating the FMR1 gene and compensating for the lack of FMRP. The latter approach has yielded promising results, with mGluR5 antagonists showing efficacy in clinical trials. CONCLUSIONS: Targeting mGluR5 is a valid approach for the development of therapeutic agents that target the underlying pathophysiology of FXS. Several compounds are currently in development, with encouraging results. PMID- 24232445 TI - The impact of missing data on clinical trials: a re-analysis of a placebo controlled trial of Hypericum perforatum (St Johns wort) and sertraline in major depressive disorder. AB - RATIONALE AND OBJECTIVE: Hypericum perforatum (St John's wort) is used to treat depression, but the effectiveness has not been established. Recent guidelines described the analysis of clinical trials with missing data, inspiring the reanalysis of this trial using proper missing data methods. The objective was to determine whether hypericum was superior to placebo in treating major depression. METHODS: A placebo-controlled, randomized clinical trial was conducted for 8 weeks to determine the effectiveness of hypericum or sertraline in reducing depression, measured using the Hamilton depression scale.We performed sensitivity analyses under different assumptions about the missing data process. RESULTS: Three hundred forty participants were randomized, with 28 % lost to follow-up. The missing data mechanism was not missing completely at random. Under missing at random assumptions, some sensitivity analyses found no difference between either treatment armand placebo, while some sensitivity analyses found a significant difference from baseline to week 8 between sertraline and placebo (-1.28, 95 % credible interval [-2.48; -0.08]), but not between hypericum and placebo (0.56, [ 0.64;1.76]). The results were similar when the missing data process was assumed to be missing not at random. CONCLUSIONS: There is no difference between hypericum and placebo, regardless of the assumption about the missing data process. There is a significant difference between sertraline and placebo with some statistical-methods used. It is important to conduct an analysis that takes account of missing data using valid statistically principled methods. The assumptions about the missing data process could influence the results. PMID- 24232447 TI - Cerebral venous thrombosis: another heparin controversy. PMID- 24232448 TI - Protective effect of time spent walking on risk of stroke in older men. AB - BACKGROUND AND PURPOSE: Older adults have the highest risks of stroke and the lowest physical activity levels. It is important to quantify how walking (the predominant form of physical activity in older age) is associated with stroke. METHODS: A total of 4252 men from a UK population-based cohort reported usual physical activity (regular walking, cycling, recreational activity, and sport) in 1998 to 2000. Nurses took fasting blood samples and made anthropometric measurements. RESULTS: Among 3435 ambulatory men free from cardiovascular disease and heart failure in 1998 to 2000, 195 first strokes occurred during 11-year follow-up. Men walked a median of 7 (interquartile range, 3-12) hours/wk; walking more hours was associated with lower heart rate, D-dimer, and higher forced expiratory volume in 1 second. Compared with men walking 0 to 3 hours/wk, men walking 4 to 7, 8 to 14, 15 to 21, and >22 hours had age- and region-adjusted hazard ratios (95% confidence intervals) for stroke of 0.89 (0.60-1.31), 0.63 (0.40-1.00), 0.68 (0.35-1.32), and 0.36 (0.14-0.91), respectively, P (trend)=0.006. Hazard ratios were somewhat attenuated by adjustment for established and novel risk markers (inflammatory and hemostatic markers and cardiac function [N-terminal pro-brain natriuretic peptide]) and walking pace, but linear trends remained. There was little evidence for a dose-response relationship between walking pace and stroke; comparing average pace or faster to a baseline of slow pace, the hazard ratio for stroke was 0.65 (95% confidence interval, 0.44-0.97), which was fully mediated by time spent walking. CONCLUSIONS: Time spent walking was associated with reduced risk of onset of stroke in dose-response fashion, independent of walking pace. Walking could form an important part of stroke-prevention strategies in older people. PMID- 24232446 TI - FoxO transcription factors: their roles in the maintenance of skeletal muscle homeostasis. AB - Forkhead box class O family member proteins (FoxOs) are highly conserved transcription factors with important roles in cellular homeostasis. The four FoxO members in humans, FoxO1, FoxO3, FoxO4, and FoxO6, are all expressed in skeletal muscle, but the first three members are the most studied in muscle. In this review, we detail the multiple modes of FoxO regulation and discuss the central role of these proteins in the control of skeletal muscle plasticity. FoxO1 and FoxO3 are key factors of muscle energy homeostasis through the control of glycolytic and lipolytic flux, and mitochondrial metabolism. They are also key regulators of protein breakdown, as they modulate the activity of several actors in the ubiquitin-proteasome and autophagy-lysosomal proteolytic pathways, including mitochondrial autophagy, also called mitophagy. FoxO proteins have also been implicated in the regulation of the cell cycle, apoptosis, and muscle regeneration. Depending of their activation level, FoxO proteins can exhibit ambivalent functions. For example, a basal level of FoxO factors is necessary for cellular homeostasis and these proteins are required for adaptation to exercise. However, exacerbated activation may occur in the course of several diseases, resulting in metabolic disorders and atrophy. A better understanding of the precise functions of these transcriptions factors should thus lead to the development of new therapeutic approaches to prevent or limit the muscle wasting that prevails in numerous pathological states, such as immobilization, denervated conditions, neuromuscular disease, aging, AIDS, cancer, and diabetes. PMID- 24232449 TI - Time to brain imaging in acute stroke is improving: secondary analysis of the INSTINCT trial. AB - BACKGROUND AND PURPOSE: Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors. METHODS: The Increasing Stroke Treatment through Interventional behavioral Change Tactics (INSTINCT) trial was a cluster-randomized, controlled trial involving 24 Michigan hospitals. The intervention aimed to increase tissue-type plasminogen activator utilization. Detailed chart abstractions collected data for 557 patients with ischemic stroke. We used a series of hierarchical linear mixed-effects models to evaluate the effect of the intervention on DIT (difference-in-differences analysis) and used patient-level and hospital-level explanatory variables to decompose variation in DIT. RESULTS: DIT improved over time, without a difference between intervention and control hospitals (intervention: 23.7-19.3 minutes, control: 28.9-19.2 minutes; P=0.56). Adjusted DIT was faster in patients who arrived by ambulance (7.2 minutes; 95% confidence interval, 4.1-10.2), had severe strokes (1.0 minute per +5-point National Institutes of Health Stroke Scale; 95% confidence interval, 0.1-2.0), and presented in the postintervention period (4.9 minutes; 95% confidence interval, 2.3-7.4). After accounting for these factors, 13.8% of variation in DIT was attributable to hospital. Neither hospital stroke volume nor stroke center status was associated with DIT. CONCLUSIONS: Performance on DIT improved similarly in intervention and control hospitals, suggesting that nonintervention factors explain the improvement. Hospital-level factors explain a modest proportion of variation in DIT, but further research is needed to identify the hospital-level factors responsible. PMID- 24232450 TI - Anticoagulants for cerebral venous thrombosis: harmful to patients? PMID- 24232451 TI - Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats. AB - Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia. PMID- 24232453 TI - Acidic residue Glu199 increases SUMOylation level of nuclear hormone receptor NR5A1. AB - Steroidogenic factor 1 (NR5A1/SF1) is a well-known master regulator in controlling adrenal and sexual development, as well as regulating numerous genes involved in adrenal and gonadal steroidogenesis. Several studies including ours have demonstrated that NR5A1 can be SUMOylated on lysine 194 (K194, the major site) and lysine 119 (K119, the minor site), and the cycle of SUMOylation regulates NR5A1's transcriptional activity. An extended consensus negatively charged amino acid-dependent SUMOylation motif (NDSM) enhances the specificity of substrate modification by SUMO has been reported; however, the mechanism of NDSM for NR5A1 remains to be clarified. In this study, we investigated the functional significance of the acidic residue located downstream from the core consensus SUMO site of NR5A1. Here we report that E199A (glutamic acid was replaced with alanine) of NR5A1 reduced, but not completely abolished, its SUMOylation level. We next characterized the functional role of NR5A1 E199A on target gene expression and protein levels. We found that E199A alone, as well as combination with K194R, increased Mc2r and Cyp19a1 reporter activities. Moreover, E199A alone as well as combination with K194R enhanced NR5A1-mediated STAR protein levels in mouse adrenocortical cancer Y1 cells. We also observed that E199A increased interaction of NR5A1 with CDK7 and SRC1. Overall, we provide the evidence that the acidic residue (E199) located downstream from the core consensus SUMO site of NR5A1 is, at least in part, required for SUMOylation of NR5A1 and for its mediated target gene and protein expression. PMID- 24232454 TI - Comparative analysis of flower volatiles from nine citrus at three blooming stages. AB - Volatiles from flowers at three blooming stages of nine citrus cultivars were analyzed by headspace-solid phase microextraction (HS-SPME)-GC-MS. Up to 110 volatiles were detected, with 42 tentatively identified from citrus flowers for the first time. Highest amounts of volatiles were present in fully opened flowers of most citrus, except for pomelos. All cultivars were characterized by a high percentage of either oxygenated monoterpenes or monoterpene hydrocarbons, and the presence of a high percentage of nitrogen containing compounds was also observed. Flower volatiles varied qualitatively and quantitatively among citrus types during blooming. Limonene was the most abundant flower volatile only in citrons; alpha-citral and beta-citral ranked 2nd and 3rd only for Bergamot, and unopened flowers of Ponkan had a higher amount of linalool and beta-pinene while much lower amount of gamma-terpinene and p-cymene than Satsuma. Taking the average of all cultivars, linalool and limonene were the top two volatiles for all blooming stages; beta-pinene ranked 3rd in unopened flowers, while indole ranked 3rd for half opened and fully opened flower volatiles. As flowers bloomed, methyl anthranilate increased while 2-hexenal and p-cymene decreased. In some cases, a volatile could be high in both unopened and fully opened flowers but low in half opened ones. Through multivariate analysis, the nine citrus cultivars were clustered into three groups, consistent with the three true citrus types. Furthermore, an influence of blooming stages on clustering was observed, especially with hybrids Satsuma and Huyou. Altogether, it was suggested that flower volatiles can be suitable markers for revealing the genetic relationships between citrus cultivars but the same blooming stage needs to be strictly controlled. PMID- 24232455 TI - Supramolecular luminescence from oligofluorenol-based supramolecular polymer semiconductors. AB - Supramolecular luminescence stems from non-covalent exciton behaviors of active pi-segments in supramolecular entities or aggregates via intermolecular forces. Herein, a pi-conjugated oligofluorenol, containing self-complementary double hydrogen bonds, was synthesized using Suzuki coupling as a supramolecular semiconductor. Terfluorenol-based random supramolecular polymers were confirmed via concentration-dependent nuclear magnetic resonance (NMR) and dynamic light scattering (DLS). The photoluminescent spectra of the TFOH-1 solution exhibit a green emission band (g-band) at approximately ~520 nm with reversible features, as confirmed through titration experiments. Supramolecular luminescence of TFOH-1 thin films serves as robust evidence for the aggregates of g-band. Our results suggest that the presence of polyfluorene ketone defects is a sufficient condition, rather than a sufficient-necessary condition for the g-band. Supramolecular electroluminescence will push organic devices into the fields of supramolecular optoelectronics, spintronics, and mechatronics. PMID- 24232452 TI - The NO/ONOO-cycle as the central cause of heart failure. AB - The NO/ONOO-cycle is a primarily local, biochemical vicious cycle mechanism, centered on elevated peroxynitrite and oxidative stress, but also involving 10 additional elements: NF-kappaB, inflammatory cytokines, iNOS, nitric oxide (NO), superoxide, mitochondrial dysfunction (lowered energy charge, ATP), NMDA activity, intracellular Ca(2+), TRP receptors and tetrahydrobiopterin depletion. All 12 of these elements have causal roles in heart failure (HF) and each is linked through a total of 87 studies to specific correlates of HF. Two apparent causal factors of HF, RhoA and endothelin-1, each act as tissue-limited cycle elements. Nineteen stressors that initiate cases of HF, each act to raise multiple cycle elements, potentially initiating the cycle in this way. Different types of HF, left vs. right ventricular HF, with or without arrhythmia, etc., may differ from one another in the regions of the myocardium most impacted by the cycle. None of the elements of the cycle or the mechanisms linking them are original, but they collectively produce the robust nature of the NO/ONOO-cycle which creates a major challenge for treatment of HF or other proposed NO/ONOO cycle diseases. Elevated peroxynitrite/NO ratio and consequent oxidative stress are essential to both HF and the NO/ONOO-cycle. PMID- 24232456 TI - Superior mechanical properties of double-network hydrogels reinforced by carbon nanotubes without organic modification. AB - A facile method is developed to fabricate nanocomposite double-network (DN) gels with excellent mechanical properties, which do not fracture upon loading up to 78 MPa and a strain above 0.98, by compositing of carbon nanotubes (CNTs) without organic modification. Investigations of swelling behaviors, and compressive and tensile properties indicate that equilibrium swelling ratio, compressive modulus and stress, fracture stress, Young's modulus, and yield stress are significantly improved in the presence of CNTs. Scanning electron microscopy (SEM) reveals that the pore size of nanocomposite DN gels is decreased and some embedded micro network structures are observed on the fracture surface in comparison to DN gels without CNTs, which leads to the enhancement of mechanical properties. The compressive loading-unloading behaviors show that the area of hysteresis loop, dissipated energy, for the first compressive cycle, increases with addition of CNTs, which is much higher than that for the successive cycles. Furthermore, the energy dissipation mechanism, similar to the Mullins effect observed in filled rubbers, is demonstrated for better understanding the nanocomposite DN polymer gels with CNTs. PMID- 24232457 TI - New benzo[c]phenanthridine and benzenoid derivatives, and other constituents from Zanthoxylum ailanthoides: Effects on neutrophil pro-inflammatory responses. AB - A new benzo[c]phenanthridine, oxynorchelerythrine (1), and two new benzenoid derivatives, methyl 4-(2-hydroxy-4-methoxy-3-methyl-4-oxobutoxy)benzoate (2) and (E)-methyl 4-(4-((Z)-3-methoxy-3-oxoprop-1-enyl)phenoxy)-2-methylbut-2-enoate (3), have been isolated from the twigs of Zanthoxylum ailanthoides, together with 11 known compounds (4-14). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, decarine (4), (-)-syringaresinol (6), (+)-episesamin (8), glaberide I (9), (-) dihydrocubebin (10), and xanthyletin (11) exhibited potent inhibition (IC50 values <= 4.79 ug/mL) of superoxide anion generation by human nutrophils in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 4, 8, and 11 also inhibited fMLP/CB-induced elastase release with IC50 values <= 5.48 ug/mL. PMID- 24232459 TI - Prevalence and risk factors associated with low-impact fractures in men with rheumatoid arthritis. AB - The aim of this study is to describe the prevalence of fractures in men with rheumatoid arthritis (RA) and identify potential risk factors associated with skeletal fragility. We consecutively studied 50 men with RA. Clinical risk factors were evaluated by clinical questionnaire, functional capacity by M-HAQ1, and disease activity by DAS-28. RA men were compared to 52 healthy controls paired for age and BMI. Bone mineral density (BMD) and quantitative ultrasound (QUS) at the heel were performed in all participants. Morphometric vertebral fractures (VF) were classified by a semiquantitative method. Men with RA were 51.7 years old on average and had mean disease duration of 115 months. Fragility fractures were found in 40% of individuals, of which 36% were VF, significantly higher than in healthy controls (p < 0.01). Age, anthropometric data, and lifestyle were similar between RA men with and without fractures. About 94% of the men with RA were on long-term glucocorticoid (GC) use. Patients with fractures were more frequently positive for rheumatoid factor (RF), had longer morning stiffness, and higher DAS-28 when compared to patients without fractures (p <= 0.05). In addition, they had significantly lower spine and hip BMD as well as a lower stiffness index (p <= 0.05). There was no statistically significant correlation between fracture and cumulative GC use. The final model of logistic regression showed a significant association and interaction between lower weight and physical activity in men with RA and fragility fractures. RA in men as well as in women is a risk factor for fragility fractures. The risk of fractures is higher in patients with positive RF, prolonged morning stiffness, higher scores of disease activity, and lower values of BMD and QUS. PMID- 24232460 TI - Sunitinib indirectly enhanced anti-tumor cytotoxicity of cytokine-induced killer cells and CD3+CD56+ subset through the co-culturing dendritic cells. AB - Cytokine-induced killer (CIK) cells have reached clinical trials for leukemia and solid tumors. Their anti-tumor cytotoxicity had earlier been shown to be intensified after the co-culture with dendritic cells (DCs). We observed markedly enhanced anti-tumor cytotoxicity activity of CIK cells after the co-culture with sunitinib-pretreated DCs over that of untreated DCs. This cytotoxicity was reliant upon DC modulation by sunitinib because the direct exposure of CIK cells to sunitinib had no significant effect. Sunitinib promoted Th1-inducing and pro inflammatory phenotypes (IL-12, IFN-gamma and IL-6) in DCs at the expense of Th2 inducing phenotype (IL-13) and regulatory phenotype (PD-L1, IDO). Sunitinib treated DCs subsequently induced the upregulation of Th1 phenotypic markers (IFN gamma and T-bet) and the downregulation of the Th2 signature (GATA-3) and the Th17 marker (RORC) on the CD3+CD56+ subset of CIK cells. It concluded that sunitinib-pretreated DCs drove the CD3+CD56+ subset toward Th1 phenotype with increased anti-tumor cytotoxicity. PMID- 24232458 TI - Ionizing radiation-induced responses in human cells with differing TP53 status. AB - Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell "death" are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21(WAF1) tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents. PMID- 24232461 TI - Automatic vasculature identification in coronary angiograms by adaptive geometrical tracking. AB - As the uneven distribution of contrast agents and the perspective projection principle of X-ray, the vasculatures in angiographic image are with low contrast and are generally superposed with other organic tissues; therefore, it is very difficult to identify the vasculature and quantitatively estimate the blood flow directly from angiographic images. In this paper, we propose a fully automatic algorithm named adaptive geometrical vessel tracking (AGVT) for coronary artery identification in X-ray angiograms. Initially, the ridge enhancement (RE) image is obtained utilizing multiscale Hessian information. Then, automatic initialization procedures including seed points detection, and initial directions determination are performed on the RE image. The extracted ridge points can be adjusted to the geometrical centerline points adaptively through diameter estimation. Bifurcations are identified by discriminating connecting relationship of the tracked ridge points. Finally, all the tracked centerlines are merged and smoothed by classifying the connecting components on the vascular structures. Synthetic angiographic images and clinical angiograms are used to evaluate the performance of the proposed algorithm. The proposed algorithm is compared with other two vascular tracking techniques in terms of the efficiency and accuracy, which demonstrate successful applications of the proposed segmentation and extraction scheme in vasculature identification. PMID- 24232463 TI - Tumour immunology: dealing with regulators. PMID- 24232464 TI - T cells: adenosine maintains the numbers. PMID- 24232465 TI - Somatic hybrid plants produced by electrofusion between Solanum melongena L. and Solanum torvum Sw. AB - Somatic hybrid plants between eggplant (Solanum melongena) and Solanum torvum have been produced by the electrofusion of mesophyll protoplasts in a movable multi-electrode fusion chamber. Using hair structure as a selection criteria, we identified a total of 19 somatic hybrids, which represented an overall average of 15.3% of the 124 regenerated plants obtained in the two fusion experiments. Several morphological traits were intermediate to those of the parents, including trichome density and structure, height, leaf form and inflorescence. Cytological analyses revealed that the chromosome numbers of the somatic hybrids approximated the expected tetraploid level (2n=4x=48). Fifteen hybrid plants were homogeneous and had relatively stable chromosome numbers (46-48), while four other hybrids had variable chromosome numbers (35-48) and exhibited greater morphological variation. The hybridity of these 19 somatic hybrid plants was confirmed by analyses of phosphoglucomutase (Pgm) and esterase zymograms. PMID- 24232462 TI - Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. AB - Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease. PMID- 24232466 TI - Genetic analysis of anther culture response in wheat using aneuploid, chromosome substitution and translocation lines. AB - Marked effects of genotype on wheat anther culture response have been observed. Genetic factors have been recognised to be one of the major contributors to in vitro responses of cultured wheat tissues. In wheat anther culture, embryo induction, plant regeneration and albina/green ratio have been determined to be heritable traits. Using Chinese Spring (CS) monosomic 1D, single chromosome substitution lines of chromosome 5B or chromosome arm 5BL from Chinese Spring into six varieties, and F1 hybrids heterozygous for the 1B chromosome structure (1BL-1BS/1BL-1RS), the anther culture response was studied: genes on CS1D chromosome and 5BL chromosome arm increases the embryo frequency; gene(s) involved in regeneration ability are located on the 1RS chromosome arm; a gene increasing albina frequency is located on Chinese Spring 5B chromosome. Our results support the fact that without gametic selection, a differential development occurred from the particular classes of microspores carrying genes for higher regeneration ability. Moreover, in some crosses, a few genes with major effects were involved in determination of anther culture response. PMID- 24232467 TI - Nuclear DNA changes within Helianthus annuus L.: origin and control mechanism. AB - Previous results suggested that the amount of nuclear DNA varies in one and the same progeny of Helianthus annuus, depending on the head portion in which seeds have developed. Accordingly, cytophotometric determinations were carried out in a selfed line, after Feulgen-staining, to obtain information on the developmental stages at which DNA changes are produced and on the mechanism controlling the variation. It was found that the Feulgen absorption values of mitotic prophases in immature anthers and pistils and of meiotic prophases I are the same in any flower of the head. In contrast, the Feulgen/DNA contents of early prophases in heart-shaped embryos differ significantly, increasing from those developing at the centre of the head to those developing at its periphery, and remaining unchanged in each embryo during further development and seed germination. Variations in the number of chromosomes do not account for the differences observed in nuclear DNA contents in which sequences comprised in heterochromatic nuclear regions are involved. The Feulgen absorption values of seedlings obtained from seeds developed in different portions of single heads increase or diminish starting from those found in the mother plant. This depends on whether these latter are relatively low or high and on the gradient of seed location in the head. The variation occurring within each single progeny covers the whole range existing within the line. PMID- 24232468 TI - Rearrangement, amplification, and assortment of mitochondrial DNA molecules in cultured cells of Brassica campestris. AB - We compared Brassica campestris mitochondrial and chloroplast DNAs from whole plants and from a 2-year-old cell culture. No differences were observed in the chloroplast DNAs (cpDNAs), whereas the culture mitochondrial DNA (mtDNA) was extensively altered. Hybridization analysis revealed that the alterations are due entirely to rearrangement. At least two inversions and one large duplication are found in the culture mtDNA. The duplication element is shown to have the usual properties of a plant mtDNA high frequency "recombination repeat". The culture mtDNA exists as a complex heterogeneous population of rearranged and unrearranged molecules. Some of the culture-associated rearranged molecules are present in low levels in native plant tissue and appear to have sorted out and amplified in the culture. Other mtDNA rearrangements may have occurred de novo. In addition to alterations of the main mitochondrial genome, an 11.3 kb linear mtDNA plasmid present in whole plants is absent from the culture. Contrary to findings in cultured cells of other plants, small circular mtDNA molecules were not detected in the B. campestris cell culture. PMID- 24232469 TI - Incidence of endogenous viral genes in two strains of white leghorn chickens selected for egg production and susceptibility or resistance to Marek's disease. AB - Endogenous viral (ev) genes related to the avian leukosis virus were classified in two differentially selected strains of Leghorns in order to investigate whether such genes affect production traits. Strain K had been selected for resistance to Marek's disease (MD) and for high egg production and egg weight, whereas strain S had been selected only for MD susceptibility. Except that founders of strain K included a few commercial birds, both strains were derived from a common genetic base. DNA restriction fragment length analyses of 110 strain K and 94 strain S birds revealed the presence of 8 different ev-genes, 6 of which were identical to previously identified loci. This result was confirmed by assays for group specific antigen (gs-antigen), the product of the gag region of the ev-genes. The levels of gs-antigen in the birds closely followed what had been predicted from data obtained from previously described ev-genes. Both strains had a similar average number of ev-genes per bird (3.5 and 3.2 for strains S and K, respectively). However, strain K carried only five different ev genes while strain S carried seven. Four of these loci were present in both strains. Among the ev-genes absent or occurring less frequently in strain K were those that code either for infectious endogenous virus (ev-10 and possibly ev-19) or for the internal viral gag-proteins (ev-3). Only those ev-genes which are transcriptionally silent or which code for the viral envelope gene were present in increased frequencies in strain K. The results indicate that selection for egg traits and/or Marek's disease resistance reduces the frequency of ev-genes which produce endogenous virus or the viral gag-proteins. PMID- 24232470 TI - Predicted and realized grain yield responses to full-sib family selection in CIMMYT maize (Zea mays L.) populations. AB - The maize (Zea mays L.) improvement program of the International Maize and Wheat Improvement Center (CIMMYT) develops broad-based maize populations and, until recently, improved all of them through full-sib family selection with international testing. The purpose of this study was to estimate the genetic and genetic * environment variance components for ten of those populations and to measure expected yield improvement from full-sib selection. Mean yield ranged from 3.35-6.81 t ha(-1). For five populations the average yield in the last cycle was higher than in the initial cycles. Several populations showed no improvement or yielded less in the final cycle of selection, either because selection intensity was low or because strong selection pressure was applied simultaneously for several traits. Variation resulting from differences among family means within cycles and from interaction between families and locations within cycles were significant in all populations and cycles. Results indicate that variability among full-sib families was maintained throughout the cycles for all populations. The large sigma ge (2) /sigma g (2) ratio shown by most populations suggests that yield response per cycle could be maximized if the environments in which progenies are tested were subdivided and classified into similar subsets. The proportion of the predicted response realized in improved yield varied for each population. PMID- 24232471 TI - Mitochondrial genome diversity among cultivars of daucus carota (ssp. sativus) and their wild relatives. AB - Restriction fragment patterns of mitochondrial DNAs (mtDNAs) from 13 carrot cultivars (Daucus carota ssp. sativus), wild carrot (ssp. carota), ssp. gummifer, and D. capillifolius were compared with each other using four restriction endonucleases. The mtDNAs of the 13 carrot cultivars could be classified into three distinct types - I, II and III - and were also clearly distinguishable from the mtDNAs of wild carrot (type IV), gummifer (V) and D. capillifolius (VI). The proportions of common restriction fragments (F values) shared by two of the three mtDNA types (I, II and III) of carrot cultivars were approximately 0.5-0.6. The F values were 0.4-0.5 for mitochondrial genomes between wild carrot, ssp. gummifer and D. capillifolius. The mitochondrial genomes between wild carrot and the carrot cultivars showed closer homologies those between wild carrot, ssp. gummifer, and D. capillifolius. The diversity of the mitochondrial genomes among the carrot cultivars is too high to presume that it was generated from the cytoplasm of only one common ancestor during the relatively short history of carrot breeding. These results suggested that the three types of cytoplasms found in the carrot cultivars might have existed in a prototype of D. carota in pre historical times. PMID- 24232472 TI - Free proline contents in two different groups of rice mutants resistant to hydroxy-L-proline. AB - In four rice (Oryza sativa L.) mutants resistant to hydroxy-L-proline (Hyp), HYP101, HYP203, HYP205 and HYP210, and in their original variety, Nipponbare, free proline and Hyp contents in the seeds and in the 14-day-old seedlings have been determined. The four mutants can be divided into two groups: HYP101 and HYP203 are classified as to recessive gene and the levels of free proline are similar to that of the original variety; the second group includes mutants HYP205 and HYP210 where the Hyp resistance is transmitted heterozygously and, both in the seeds and in the seedlings, a remarkable increase in free proline content is observed. In particular, free proline contents in the seeds of HYP205 and HYP210 are, respectively, 24 and 12 times that of the original variety. Hyp is detected only in the seedlings cultured with Hyp solution. In the Hyp resistant seedlings of HYP205 and HYP210, Hyp contents are twice that of the original variety and less than half in the seedlings of HYP101 and HYP203. Hyp resistance and differential proline levels are also evident in the callus initiated from the mutants. This suggests that the Hyp resistant mutants are good genetic markers both in planta and in vitro. The Hyp mutants are also discussed with regard to stress resistance. PMID- 24232474 TI - The cumulative effect of allelic variation in LMW and HMW glutenin subunits on dough properties in the progeny of two bread wheats. AB - The effects of allelic variation at Gli-A1, GluA3 and Glu-A1 loci coding for gliadins, LMW glutenin subunits and HMW glutenin subunits on dough resistance and extensibility was analysed in 56 F2-derived F6 families from a cross between bread wheats MKR(111/8) and 'Kite'. Extensograph data from two sites giving widely different flour protein levels (approximately 7% and 14%) revealed that the Glu-A3m and Glu-A1b alleles were associated with larger effects on dough resistance and extensibility than the null alleles Glu-A3k and GluA1c, respectively, and moreover, their effects were additive at both protein levels. The effect of the LMW glutenin allele Glu-A3m on both dough resistance and dough extensibility was relatively larger than that of the HMW glutenin allele Glu-A1b at both sites. Variation at the Gli-A1 locus did not appear to contribute towards dough strength. The results also showed the large effect of flour protein content on dough properties. PMID- 24232473 TI - Somatic hybridization between anther-derived dihaploid clones of potato (Solanum tuberosum L.) and the identification of hybrid plants by isozyme analysis. AB - Green mesophyll protoplasts of the dihaploid potato line 198?2 (Solanum tuberosum L.) were fused with herbicide-bleached mesophyll protoplasts of the dihaploid potato line 67?9 using a polyethylene glycol protocol. Heterokaryons were identified under a fluorescence microscope using the dual fluorescence of carboxyfluorescein-stained, herbicide-bleached protoplasts and the autofluorescence of green mesophyll protoplasts. About 20% of the protoplasts survived the fusion treatment, and the fusion frequency was 3%-4%. Unfused and fused protoplasts were mass cultured for 6 weeks after which vigorously growing calli were selected and transferred to shoot regeneration medium. Somatic hybrids were identified by a combination of five isozyme markers, and the ploidy level was determined by flow cytometry. Out of 15 calli that regenerated shoots, 6 plants derived from 2 different calli were identified as hexaploid somatic hybrids, while one morphologically deviant plant from a third callus was identified as a mixoploid that had lost some enzyme markers after 4 months of culturing. PMID- 24232475 TI - Coexistence and the productivity of white clover-perennial ryegrass mixtures. AB - Yield comparisons between five white cloverperennial ryegrass mixtures, whose individual components had previously coexisted, and a corresponding set of ten mixtures based on components that had not coexisted disclosed a yield advantage to the former group of 8.5% over a 4-year period. All five clover populations produced their highest yields when associated with their coexisting grass. The coexisting mixtures also yielded more grass in spring, probably due to the exotic origin of the majority of the companion grasses, reinforced by the nitrogen transfer process between clover and grass. The relative proportions of clover attained by the five populations was apparently unaffected by grass companion. These results are briefly discussed in the context of improving the productivity of white clover-perennial ryegrass mixtures. PMID- 24232476 TI - Self fertilization and seed set in Trifolium repens L. by in situ and in vitro pollination. AB - The frequency of seed formation has been determined from self-pollination in situ (by hand) and in vitro for Trifolium repens. Selfing in situ was measured over a period of 3 years in which plants were held either at 35 degrees C for 24 h post pollination (1984 and 1985) or held at ambient temperatures (1986). Mean yield of self-seed per 100 florets was 2.8 in 1984, 5.2 in 1985 and 2.2 in 1986. This was based on over 15,000 selfings per year with seven varieties and a total of 166 genotypes. In general, seed set following self-pollination was low; 53% of all genotypes set less than one seed per 100 florets selfed. Selfing of 340 excised florets in vitro with six genotypes gave a mean of 30.6 seeds per 100 florets. Temperature treatments (post-pollination) had no significant effect on seed yield in vitro. Treatment of florets in vitro for 24 h post-pollination with 0.1% CO2 increased the yield of self seed with three genotypes but had no effect on a fourth genotype. PMID- 24232477 TI - Differences in response to the toxin sirodesmin PL produced by Phoma lingam (Tode ex fr.) Desm. on protoplasts, cell aggregates and intact plants of resistant and susceptible Brassica accessions. AB - The selective property of sirodesmin PL, a toxin produced by Phoma lingam, was studied on protoplasts, cell aggregates, leaves and roots. Directly after isolation, protoplasts from all the different Brassica accessions were sensitive when treated with toxin in a concentration higher than 1 MUM. When more differentiated plant tissue. i.e. cell aggregates, leaves or roots, were investigated, insensitivity to the toxin was found in the plant material resistant to P. lingam, while the plant material susceptible to P. lingam was sensitive. The results reveal that a clear correlation between resistance to P. lingam and insensitivity to sirodesmin PL is present, and that the toxin can be used to distinguish resistant plant material from susceptible both in vivo and in vitro. PMID- 24232478 TI - Identification of a 1B/1R wheat-rye chromosome translocation. AB - The common wheat selection '79-4045' was identified as a wheat-rye 1B/1R chromosome translocation line, by means of C-banding patterns and test cross with 'Chinese Spring' double-ditelosomic line. The translocation chromosome consisted of the long arm of wheat chromosome 1B, including its centromere, and the short arm of rye chromosome 1R or tis portion. PMID- 24232479 TI - Heterochromatin differentiation and phylogenetic relationship of the A genomes in diploid and polyploid wheats. AB - Heterochromatin differentiation, including band size, sites, and Giemsa staining intensity, was analyzed by the HKG (HCl-KOH-Giemsa) banding technique in the A genomes of 21 diploid (Triticum urartu, T. boeoticum and T. monococcum), 13 tetraploid (T. araraticum, T. timopheevi, T. dicoccoides and T. turgidum var. Dicoccon, Polonicum), and 7 cultivars of hexaploid (T. aestivum) wheats from different germplasm collections. Among wild and cultivated diploid taxa, heterochromatin was located mainly at centromeric regions, but the size and staining intensity were distinct and some accessions' genomes had interstitial and telomeric bands. Among wild and cultivated polyploid wheats, heterochromatin exhibited bifurcated differentiation. Heterochromatinization occurred in chromosomes 4A(t) and 7A(t) and in smaller amounts in 2A(t), 3A(t), 5A(t), and 6A(t) within the genomes of the tetraploid Timopheevi group (T. araraticum, and T. timopheevi) and vice versa within those of the Emmer group (T. dicoccoides and T. turgidum). Similar divergence patterns occurred among chromosome 4A(a) and 7A(a) of cultivars of hexaploid wheat (T. aestivum). These dynamic processes could be related to geographic distribution and to natural and artifical selection. Comparison of the A genomes of diploid wheats with those of polyploid wheats shows that the A genomes in existing diploid wheats could not be the direct donors of those in polyploid wheats, but that the extant taxa of diploids and polyploids probably have a common origin and share a common A-genomelike ancestor. PMID- 24232480 TI - Restriction fragment length polymorphism maps and the concept of graphical genotypes. AB - With the advent of high density restriction fragment length polymorphism (RFLP) maps, it has become possible to determine the genotype of an individual at many genetic loci simultaneously. Often, such RFLP data are expressed as long strings of numbers or letters indicating the genotype for each locus analyzed. In this form, RFLP data can be difficult to interpret or utilize without complex statistical analysis. By contrast, numerical genotype data can also be expressed in a more useful, graphical form, known as a "graphical genotype", which is described in detail in this paper. Ideally, a graphical genotype portrays the parental origin and allelic composition throughout the entire genome, yet is simple to comprehend and utilize. In order to demonstrate the usefulness of this concept, graphical genotypes for individuals from backcross and F2 populations in tomato are described. The concept can also be utilized in more complex mating schemes involving two or more parents. A model that predicts the accuracy of graphical genotypes is presented for hypothetical RFLP maps of varying marker spacing. This model indicates that graphical genotypes can be more than 99% correct in describing a genome of total size, 1000 cM, with RFLP markers located every 10 cM. In order to facilitate the application of graphical genotypes to genetics and breeding, we have developed computer software that generates and manipulates graphical genotypes. The concept of graphical genotypes should be useful in whole genome selection for polygenic traits in plant and animal breeding programs and in the diagnosis of heterogenously based genetic diseases in humans. PMID- 24232481 TI - Flow cytometric and karyological analysis of polysomaty and polyploidization during callus formation from leaf segments of various potato genotypes. AB - Flow cytometry and karyological analysis were used to study polysomaty and polyploidization during the first 15 days of callus formation in leaf segments from shoot cultures and greenhouse-grown plants of various lines and genotypes of Solanum tuberosum and S. phureja. The greenhouse-grown plants showed a higher degree of polysomaty (77% and 49% of polyploidized nuclei) than the shoot cultures (< 3%). During the in vitro culture period, polyploidization occurred through endoreduplication. Segments of the five shoot cultures showed up to 87%, 53%, 59%, 45% and 56% polyploidization, respectively; the DNA content of corresponding interphase nuclei amounted to 8C, 16C, 16C, 16C and 8C, and the chromosome numbers to 96. Segments from the two greenhouse-grown genotypes showed up to 87% and 84% polyploidization; the DNA content amounted to 32C and 16C, and the chromosome numbers to 192 and 96. The number of reduplication cycles was species-dependent; the degree of polyploidization was dependent on the initial ploidy level of the genotypes. Cell proliferation did not take place at a constant rate. The maximum frequencies of metaphases (52-171 per segment) occurred after 1 week of culture and were correlated with the ploidy level of the genotypes. Cells were triggered to mitosis rather than to endoreduplication. Cell cycles with normal monochromosomes could be shorter than 1 day, and those with diplochromosomes lasted at least 1 day. Polysomaty, degree of polyploidization and abnormal nuclear processes are discussed in relation to the origin of genetic instability early in culture. PMID- 24232482 TI - An analysis of the costs and benefits of the cyanogenic system in Trifolium repens L. AB - The effect of the cyanogenic glucosides linamarin and lotaustralin and their hydrolyzing enzyme linamarase was studied in a B2 generation segregating for the genes Ac and Li. Plants containing the glucosides are protected against grazing by snails both in the seedling stage and as adult plants. In seedlings, however, there is a direct effect on survival, whereas in adult plants the leaf area of plants containing linamarin/lotaustralin is less reduced under intense grazing. Linamarase has no effect on grazing by snails, possibly as a result of the presence of beta-glucosidase activity in the gut of these animals. The genes Ac and Li, or genes tightly linked to them, have other effects as well: plants possessing one dominant Ac allele produce fewer flowers than homozygous ac plants. I compared this difference in flower production to the metabolic cost of producing the cyanogenic glucosides. The energy content of the difference in flower head production far exceeded the metabolic cost of cyanoglucoside production in Acac plants. It is possible that the cost of maintaining a certain level of cyanoglucosides is much more important for the plant than the initial cost of biosynthesis. The importance of the effects of Ac and Li in the maintenance of cyanogenic polymorphism in white clover is discussed. PMID- 24232483 TI - Expression of genetic and environmental variation during ageing : 1. Estimation of variance components for number of adult offspring in Drosophila melanogaster. AB - To test for different gene activity during ageing, an experiment was set up to determine whether or not genetic variation and genetic correlations between fitness traits at different ages change in a systematic way through time. Additive genetic and environmental variance components as well as genetic correlations between different age periods were calculated for the fitness trait "number of adult offspring" in a population of Drosophila melanogaster. Genetic correlations between age periods were all positive and, hence, did not support the theory postulating that genes with beneficial effects on early fitness have pleiotropic unfavourable effects on late fitness. The environmental variation as well as the additive genetic variance showed a clear increase with age. The increase of environmental variation is probably a result of the individuals' increasing difficulties in coping with environmental stress due to physiological deterioration with age. Increased additive genetic variation may be explained by more and more genes being "turned on" with age. Alternatively, it could be caused by accumulation of deleterious mutations with different effects and may reflect the individuals' capacity of DNA repair. PMID- 24232484 TI - Effect of rate of inbreeding on inbreeding depression in Drosophila melanogaster. AB - This experiment was designed to study the relationship between rate of inbreeding and observed inbreeding depression of larval viability, adult fecundity and cold shock mortality in Drosophila melanogaster. Rates of inbreeding used were full sib mating and closed lines of N=4 and N=20. Eight generations of mating in the N=20 lines, three generations in the N=4 lines and one generation of full-sib mating were synchronised to simultaneously produce individuals with an expected level of inbreeding coefficient (F) of approximately 0.25. Inbreeding depression for the three traits was significant at F=0.25. N=20 lines showed significantly less inbreeding depression than full-sib mated lines for larval viability at approximately the same level of F. A similar trend was observed for fecundity. No effect of rate of inbreeding depression was found for cold shock mortality, but this trait was measured with less precision than the other two. Natural selection acting on loci influencing larval viability and fecundity during the process of inbreeding could explain these results. Selection is expected to be more effective with slow rates of inbreeding because there are more generations and greater opportunity for selection to act before F=0.25 is reached. Selection intensities seem to have been different in the three traits measured. Selection was most intense for larval viability, less intense for fecundity and, perhaps, negligible at loci influencing cold shock mortality. PMID- 24232485 TI - Population selection to maximize value in an environmental gradient. AB - A theory for determining optimum planting and breeding zones is described. The theory is based on a model consisting of Gaussian response functions for traits that vary in a gradient for a single environmental variable. Environments are assumed to be normally distributed with known mean and variance. Methods are presented for determining parameters of response functions that maximize the expected value for such a trait when two, three and four populations are selected for breeding or as sources of propagules. Expected value is maximized only when the populations selected have response functions symmetrically arrayed about the mean of the environmental variable. Maximum expected value was shown to increase with increasing number of selected populations at a rate that depends upon the ratio of homostasis to environmental variability. The methods presented are illustrated with data on performance of Scots pine provenances in Sweden. PMID- 24232486 TI - Correction of chlorophyll-defective male-sterile winter oilseed rape (Brassica napus) through organelle exchange: molecular analysis of the cytoplasm of parental lines and corrected progeny. AB - Cytoplasmic differences between male-fertile and male-sterile Brassica napus as well as Raphanus sativus were investigated. Plastids of the male-fertile B. napus were found to differ from those of male-sterile B. napus and R. sativus with respect to DNA restriction enzyme patterns. Differences between male-fertile and male-sterile B. napus mitochondria were detected not only in the restriction fragment patterns of their DNA, but also at the level of expression by in organello translation of mitochondrial polypeptides.The chlorophyll deficiency obtained upon transferral of the male-sterility-conferring radish cytoplasm to a winter variety of B. napus had been corrected earlier through protoplast fusion. The cytoplasmic composition of the corrected lines was analysed using DNA restriction analysis and in organello translation. The stability of the recombined cytoplasm in the corrected lines was confirmed by analysis of the subsequent seed-derived generation. PMID- 24232487 TI - Effect of mass selection on the within-family genetic variance in finite populations. AB - The adequacy of an expression for the withinfamily genetic variance under pure random drift in an additive infinitesimal model was tested via simulation in populations undergoing mass selection. Two hundred or one thousand unlinked loci with two alleles at initial frequencies of 1/2 were considered. The size of the population was 100 (50 males and 50 females). Full-sib matings were carried out for 15 generations with only one male and one female chosen as parents each generation, either randomly or on an individual phenotypic value. In the unselected population, results obtained from 200 replicates were in agreement with predictions. With mass selection, within-family genetic variance was overpredicted by theory from the 12th and 4th generations for the 1,000 and 200 loci cases, respectively. Taking into account the observed change in gene frequencies in the algorithm led to a much better agreement with observed values. Results for the distribution of gene frequencies and the withinlocus genetic covariance are presented. It is concluded that the expression for the within family genetic variance derived for pure random drift holds well for mass selection within the limits of an additive infinitesimal model. PMID- 24232488 TI - A new approach to chromosome doubling for haploid rice plants. AB - Rice nodal segments from three flowering haploids were excised and treated for different lengths of time with 0.3% or 0.4% colchicine (dissolved in 2% DMSO) in an attempt to induce fertile seeds. A combination of higher colchicine concentration and longer hours of treatment reduced the survival rate of treated segments, but more fertile plants were transformed. Pooled data showed that of the 842 segments used, 42.2% survived the treatment and sprouted, but only 31.9% were successfully established and grown to maturity. Among the 269 mature plants, 29,4% produced fertile seeds (panicles) with an average of 146.2 seeds per diploidized plant. PMID- 24232489 TI - Marked recovery of vision in children with optic pathway gliomas treated with bevacizumab. AB - IMPORTANCE: Children with optic pathway gliomas (OPGs) frequently experience vision loss from their tumors. Standard front-line treatment using carboplatin based chemotherapy typically produces only a modest benefit (eg, stabilization or 0.2 logMAR improvement) in visual acuity (VA). Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor and acts primarily as an anti-angiogenic agent. Recent reports suggest a qualitative improvement in vision after bevacizumab-based treatment in children with OPGs. OBSERVATIONS: We report 4 cases of pediatric OPGs (2 neurofibromatosis type 1-related and 2 sporadic cases) that received treatment with bevacizumab due to progressive VA or visual field (VF) loss despite prior treatment with chemotherapy or proton-beam radiation. All 4 subjects demonstrated a marked improvement in their VA, VF, or both while receiving bevacizumab-based therapy. Three patients had complete resolution of their VA or VF loss in at least 1 eye-2 of whom had previously received bevacizumab therapy. CONCLUSIONS AND RELEVANCE: Given that most patients with OPG-related visual impairment will show modest or no visual improvement with standard treatment, the incorporation of bevacizumab in these cases may greatly improve visual outcomes and should be considered in appropriate clinical situations. PMID- 24232490 TI - Temperature effects on steady-state growth, phosphorus uptake, and the chemical composition of a marine phytoplankter. AB - The marine chrysophyteMonochrysis lutheri was grown in phosphorus-limited continuous cultures at temperatures of 15 degrees , 18.8 degrees and 23 degrees C. The effect of temperature on the maximum growth rate was well-defined by the Arrhenius equation, but the Q10 for this alga (1.7) was somewhat lower than has been determined previously for many other phytoplankton species (2.0-2.2). The minimum phosphorus cell quota was relatively unaffected by temperature at 18.8 degrees C and 23 degrees C, but doubled in magnitude at 15 degrees C. As a result, the internal nutrient equation of Droop described the relationship between specific growth rate and phosphorus cell quota well at 18.8 degrees and 23 degrees C, but was less successful at 15 degrees C. The major limitation in using the Droop equation is that the ratio between the minimum and maximum cell quotas must be known, thus necessitating the need to establish the true maximum growth rate by the cell washout technique. In addition, the phosphorus uptake rate on a cell basis at a given steady state growth rate (=specific uptake rate) increased dramatically at 15 degrees C, whereas the turnover rate of total available phosphorus was unaffected by temperature. Both the nitrogen and carbon cell quotas were relatively unaffected by growth rate at a given temperature, but the average values increased slightly with decreasing temperature. The overall conclusion is that phytoplankton growth and limiting-nutrient uptake rates are only synchronous at or near the optimum temperature. Because these types of responses are species specific, much additional data on temperature effects will be required before the importance of including such effects in phytoplankton nutrient models can be determined. PMID- 24232491 TI - Cellulolytic bacteria as primary colonizers ofPotamogeton pectinatus L. (Sago Pond Weed) from a Brackish South-Temperate Coastal Lake. AB - Bacteria adhering to newly emerged and decomposing leaves ofPotamogeton pectinatus L. were examined using scanning electron microscopy. Bacteria obtained from mature leaves were isolated, grown in pure culture, and allowed to infect bacteria-free leaves. Infected leaves and individual isolates were examined by scanning electron microscopy. The method provided detail of the forms of bacterial attachment to leaf surfaces.Supernatants from isolate cultures were assayed for cellulase activity. Six out of eight isolates produced extracellular cellulase in medium containing carboxymethyl cellulose. In one isolate cellulase was produced at discrete intervals, at the beginning and end of the growth cycle. The adhesion of the isolates toP. pectinatus leaves, as well as their possession of cellulase, are considered as evidence of an active role of bacteria in the degradation ofP. pectinatus foliage. The system is unusual in that bacteria, as opposed to fungi, are primary colonizers of the leaves. PMID- 24232492 TI - Ecology ofAeromonas hydrophila in a South Carolina cooling reservoir. AB - Densities ofAeromonas hydrophila were determined monthly from December 1975 to December 1977 in a South Carolina cooling reservoir which receives heated effluent from a single nuclear production reactor. Selected water quality parameters and prevalence of red-sore disease among largemouth bass were monitored simultaneously.Higher densities ofA. hydrophila were observed in areas of the reservoir receiving effluent from the reactor. Densities ofA. hydrophila generally were heterogeneous in the water column. The sediments had lower densities ofA. hydrophila than water immediately above.A. hydrophila could not be isolated from sediments greater than 1 cm from the water interface. Temperature, redox potential, pH, and conductivity were all significantly correlated with densities ofA. hydrophila in the water column. The temporal and spatial distribution and abundance ofA. hydrophila in water were not related to total organic carbon, dissolved organic carbon, particulate organic carbon, inorganic carbon, or dissolved oxygen. High densities ofA. hydrophila were observed in mats of decomposingMyriophyllum spicatum and, enterically, in largemouth bass, several other species of fish, turtles, alligators, and snails. The greatest densities ofA. hydrophila in water occurred during March and June with a second peak in October. The mean monthly densities ofA. hydrophila were positively correlated with the incidence of infection in largemouth bass. Largemouth bass from thermally altered parts of the reservoir had a significantly higher incidence of infection. It is concluded that thermal effluent significantly affects the ecology ofA. hydrophila and the epizootiology of red-sore disease within Par Pond. PMID- 24232493 TI - Isolation from soils ofNitrobacter and evidence for novel serotypes using immunofluorescence. AB - To study the ecology of chemoautotrophic nitrifying bacteria (Nitrobacter), the immunofluorescence technique has been used. Fluorescent antibodies againstNitrobacter winogradskyi andNitrobacter agilis, the two known serotypes, have not labeled strains isolated from soils of the Lyon region (pH 8.1 and pH 4.7). The pure-culture isolates appeared to belong to the same genus, but to be serologically different from the reference strains. These results led us to question the diversity of strains ofNitrobacter in soils. PMID- 24232494 TI - Michaelis constant (K m ) of acid phospatase as affected by montmorillonite, illite, and kaolinite clay minerals. AB - The influence of Ca homoionic clay minerals (montmorillonite, illite, and kaolinite) on the activity,K m , andV m values of acid phosphatase was examined in model experiments. At each substrate (p-nitrophenyl phosphate) level tested, the addition of increasing amounts of clays (50, 100, and 150 mg, respectively) decreased the activity and increased theK m value from 1.43*10(-3) M PNP (in the soluble state) to 82.3*10(-3)M (montmorillonite), 8.02*10(-3) M (kaolinite), and 7.65*10(-3) M (illite) at the 150 mg level. The maximum enzyme reaction velocity (V m ) remained nearly constant at different amounts of kaolinite and illite, but increased remarkably with rising quantities of montmorillonite. Apparently, the substrate affinity of sorbed acid phosphatase is significantly lower with montmorillonite than with kaolinite or illite. This may be ascribed to an intensive sorption of both substrate and enzyme to the surface as well as to interlattice sites of montmorillonite. PMID- 24232495 TI - Observations on naturally and artificially diseased tropical corals: A scanning electron microscope study. AB - Scanning electron microscopic (SEM) observations of naturally and artificially diseased corals reveal that the disease is characterized by a filamentous matrix of cyanobacterial andBeggiatoa filaments. Spiral bacteria are commonly embedded in the matrix. The artificial disease is not manifested as the characteristic "black line disease" and does not contain filaments of cyanobacteria. This suggests that cyanobacteria are necessary for the black line phenomenon. The colorless, sulfide-oxidizing bacteriumBeggiatoa, however, is always associated with the disease. PMID- 24232496 TI - Grazing by protozoa as selection factor for activated sludge bacteria. AB - In continuous culture enrichments that were inoculated with activated sludge and were fed with polymeric substrates, freely dispersed single-celled bacteria belonging to theCytophaga group dominated among the initial populations, irrespective of the activated sludge source. These populations were grazed by flagellated protozoa which after several days reached high cell densities. Other morphologic bacterial groups such as spiral-shaped or filamentous bacteria then became dominant. In defined mixed culture experiments with bacterial isolates from the enrichment cultures, it was shown that a "grazing-resistant"Microcyclus strain outgrew aCytophaga strain in the presence of grazing protozoa. In contrast, theCytophaga strain competed successfully with theMicrocyclus strain and with other "grazing-resistant" strains under protozoa-free conditions. Furthermore, it was demonstrated that assumed grazing resistance factors such as floccing or filamentous growth were lost by some of the strains when they were grown for several generations in continuous culture under the same conditions, but in the absence of protozoa. PMID- 24232497 TI - Circadian rhythmicity as a predictor of weight-loss effectiveness. AB - OBJECTIVES: Some of the major challenges associated with successful dietary weight management include the identification of individuals not responsive to specific interventions. The aim was to investigate the potential relationship between weight loss and circadian rhythmicity, using wrist temperature and actimetry measurements, in women undergoing a weight-loss program, in order to assess whether circadian rhythmicity could be a marker of weight-loss effectiveness. METHODS: Participants were 85 overweight and obese women (body mass index, BMI: 30.24+/-4.95 kg m(-2)) subjected to a weight-reduction program. Efficacy of the treatment was defined as total weight loss, percentage of initial weight and weekly weight loss rates. Circadian rhythmicity in wrist temperature motor activity and position were analyzed using different sensors. RESULTS: Lower weight loss was related with a more flattened pattern measured as amplitude from cosinor (r=0.235, P=0.032), a higher fragmentation of rhythms determined by higher intradaily variability (IV) (r=-0.339, P=0.002), and an impaired wrist temperature circadian rhythm determined by the means of Circadian Function Index (r=0.228, P=0.038). Further analyses showed that low responders displayed lower amplitude (0.71+/-0.36 versus 1.24+/-0.62, P=0.036) and higher fragmentation of the circadian rhythm (0.24+/-0.11 versus 0.15+/-0.07, P=0.043) than high responders. Whereas we did not find significant differences in total activity rates between high responders and low responders, we found significant differences for the mean values of body position for high responders (39.12+/ 3.79 degrees ) as compared with low responder women (35.31+/-2.53 degrees , P=0.01). CONCLUSIONS: Circadian rhythms at the beginning of the treatment are good predictors of future weight loss. Further treatment should consider chronobiological aspects to diagnose obesity and effectiveness of treatments. PMID- 24232499 TI - Obesity and muscle strength as long-term determinants of all-cause mortality--a 33-year follow-up of the Mini-Finland Health Examination Survey. AB - OBJECTIVE: To examine the independent and combined associations of obesity and muscle strength with mortality in adult men and women. DESIGN: Follow-up study with 33 years of mortality follow-up. SUBJECTS: A total of 3594 men and women aged 50-91 years at baseline with 3043 deaths during the follow-up. MEASUREMENT: Body mass index (BMI) and handgrip strength were measured at baseline. RESULTS: Based on Cox models adjusted for age, sex, education, smoking, alcohol use, physical activity and chronic conditions, baseline obesity (BMI >=30 kg m(-2)) was associated with mortality among participants aged 50-69 years (hazard ratio (HR) 1.14, 95% confidence interval (CI), 1.01-1.28). Among participants aged 70 years and older, overweight and obesity were protective (HR 0.77, 95% CI, 0.66 0.89 and HR 0.76, 95% CI, 0.62-0.92). High handgrip strength was inversely associated with mortality among participants aged 50-69 (HR 0.89, 95% CI, 0.80 1.00) and 70 years and older (HR 0.78, 95% CI, 0.66-0.93). Compared to normal weight participants with high handgrip strength, the highest mortality risk was observed among obese participants with low handgrip strength (HR 1.23, 95% CI, 1.04-1.46) in the 50-69 age group and among normal-weight participants with low handgrip strength (HR 1.30, 95% CI, 1.09-1.54) among participants aged 70+ years. In addition, in the old age group, overweight and obese participants with high handgrip strength had significantly lower mortality than normal-weight participants with high handgrip strength (HR 0.79, 95% CI, 0.67-0.92 and HR 0.77, 95% CI, 0.63-0.94). CONCLUSION: Both obesity and low handgrip strength, independent of each other, predict the risk of death in adult men and women with additive pattern. The predictive value of obesity varies by age, whereas low muscle strength predicts mortality in all age groups aged>50 years and across all BMI categories. When promoting health among older adults, more attention should be paid to physical fitness in addition to body weight and adiposity. PMID- 24232498 TI - The small molecule indirubin-3'-oxime activates Wnt/beta-catenin signaling and inhibits adipocyte differentiation and obesity. AB - OBJECTIVES: Activation of the Wnt/beta-catenin signaling pathway inhibits adipogenesis by maintaining preadipocytes in an undifferentiated state. We investigated the effect of indirubin-3'-oxime (I3O), which was screened as an activator of the Wnt/beta-catenin signaling, on inhibiting the preadipocyte differentiation in vitro and in vivo. METHODS: 3T3L1 preadipocytes were differentiated with 0, 4 or 20 MUM of I3O. The I3O effect on adipocyte differentiation was observed by Oil-red-O staining. Activation of Wnt/beta catenin signaling in I3O-treated 3T3L1 cells was shown using immunocytochemical and immunoblotting analyses for beta-catenin. The regulation of adipogenic markers was analyzed via real-time reverse transcription-PCR (RT-PCR) and immunoblotting analyses. For the in vivo study, mice were divided into five different dietary groups: chow diet, high-fat diet (HFD), HFD supplemented with I3O at 5, 25 and 100 mg kg(-1). After 8 weeks, adipose and liver tissues were excised from the mice and subject to morphometry, real-time RT-PCR, immunoblotting and histological or immunohistochemical analyses. In addition, adipokine and insulin concentrations in serum of the mice were accessed by enzyme linked immunosorbent assay. RESULTS: Using a cell-based approach to screen a library of pharmacologically active small molecules, we identified I3O as a Wnt/beta-catenin pathway activator. I3O inhibited the differentiation of 3T3-L1 cells into mature adipocytes and decreased the expression of adipocyte markers, CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma, at both mRNA and protein levels. In vivo, I3O inhibited the development of obesity in HFD-fed mice by attenuating HFD-induced body weight gain and visceral fat accumulation without showing any significant toxicity. Factors associated with metabolic disorders such as hyperlipidemia and hyperglycemia were also improved by treatment of I3O. CONCLUSION: Activation of the Wnt/beta-catenin signaling pathway can be used as a therapeutic strategy for the treatment of obesity and metabolic syndrome and implicates I3O as a candidate anti-obesity agent. PMID- 24232501 TI - The relationship between family functioning and child and adolescent overweight and obesity: a systematic review. AB - There is mounting evidence that family functioning is linked to childhood overweight and obesity, and that both of these are associated with health-related behaviours and adverse health outcomes in children and adolescents. This paper systematically examines the peer-reviewed evidence regarding the relationship between child and adolescent overweight and obesity and family functioning. Peer reviewed literature published between 1990 and 2011 hosted in Scopus, Pub Med or Psyc INFO were searched, in addition to the reference lists of included papers. Twenty-one studies met the selection criteria. Of the 17 identified cross sectional and longitudinal studies, 12 reported significant associations between family functioning and childhood overweight and obesity. The instruments used to measure family functioning in the identified studies were heterogeneous. Poor family functioning was associated with increased risk of obesity and overweight in children and adolescents, and obese children and adolescents were more likely to come from families with poor family functioning. Aspects of family functioning which were associated with increased risk of child and adolescent obesity included poor communication, poor behaviour control, high levels of family conflict and low family hierarchy values. Half (2/4) of the identified intervention studies showed a significant relationship between family functioning and changes in child weight. The results demonstrate that family functioning is linked to obesity; however, higher level evidence and greater understanding of the mechanisms behind this relationship are required. The results indicate a need for a standardised family functioning measure applicable across populations. The results provide evidence of the value of considering family functioning in childhood obesity research and intervention. PMID- 24232500 TI - Relationship between overweight and health-related quality of life in secondary school children in Fiji: results from a cross-sectional population-based study. AB - OBJECTIVE: To investigate the relationship between excess weight (overweight and obesity) and health-related quality of life (HRQoL) in a sample of secondary school children in Fiji, by gender, age and ethnicity. METHODS: The study comprised 8947 children from forms 3-6 (age 12-18 years) in 18 secondary schools on Viti Levu, the main island of Fiji. Body mass index (BMI) was calculated from measured height and weight, and weight status was classified according to the International Obesity Task Force recommendations. HRQoL was measured by the self report version of the Pediatric Quality of Life Inventory 4.0. RESULTS: HRQoL was similar in children with obesity and normal weight. Generally, this was replicated when analyzed separately by gender and ethnicity, but age stratification revealed disparities. In 12-14-year-old children, obesity was associated with better HRQoL, owing to better social and school functioning and well-being, and in 15-18-year olds with poorer HRQoL, owing to worse physical, emotional and social functioning and well-being (Cohen's d 0.2-0.3). Children with a BMI in the overweight range also reported a slightly lower HRQoL than children with a BMI in the normal weight range, but although statistically significant, the size of this difference was trivial (Cohen's d <0.2). DISCUSSION: The results suggest that, overall there is no meaningful negative association between excess weight and HRQoL in secondary school children in Fiji. This is in contradiction to the negative relationship between excess weight and HRQoL shown in studies from other countries and cultures. The assumption that a large body size is associated with a lower quality of life cannot be held universally. Although a generally low HRQoL among children in Fiji may be masking or overriding the potential effect of excess weight on HRQoL, socio-economic and/or socio-cultural factors, may help to explain these relationships. PMID- 24232502 TI - Are teachers' judgements of pupils' ability influenced by body shape? AB - BACKGROUND: Evidence indicates that teachers can judge pupils on the basis of their physical appearance, including their body shape. Teacher bias towards obese pupils has been suggested as a potential pathway through which obese children attain relatively lower academic levels. The aim of this study was to investigate whether teachers' judgements of pupils' ability are influenced by the body shape of the child. METHODS: The sample includes English, singleton children in state schools from the Millennium Cohort Study. The data were taken from the fourth wave of data collection, when the children were approximately 7 years old. In all, 5086/5072 children had teacher ability ratings of reading and maths. Logistic regression analyses were used to test whether teachers' perceptions of the child's reading and mathematics ability were influenced by the pupil's waist circumference, conditional upon cognitive test scores of reading and maths ability. RESULTS: After adjustment for cognitive test scores, no significant overall relationship was found between the pupil's waist circumference and the teacher's judgements of ability. No statistically significant differences were observed in the probability of being judged as above average after further adjustments were made for potential confounders. CONCLUSIONS: There is little evidence that teachers' judgements of pupils' ability are influenced by obesity. PMID- 24232503 TI - Assessment of ectomycorrhizal biodiversity in Tuber macrosporum productive sites. AB - Tuber macrosporum Vittad. is a truffle with superb organoleptic properties, whose cultivation is still in its infancy. For the first time we have aimed to provide information on ectomycorrhizal communities in natural and cultivated T. macrosporum sites. Ectomycorrhizal morphotypes were identified using ITS nrDNA sequencing and sorted into molecular operational taxonomic unit (MOTU). We detected 16 MOTUs in the T. macrosporum cultivated plantation. Ascomycota were the most abundant (86.4%) with Helvellaceae, Pyronemataceae and Pezizaceae the most common. Twenty-two MOTUs were collected in the natural T. macrosporum site. Basidiomycota morphotypes were plentiful (70.6%) and Thelephoraceae dominated. Each site had different taxa belowground with only T. macrosporum in common, being more abundant in the natural (18.2%) than in the cultivated (14.4%) site. Species richness, Simpson and Shannon diversity indices, taxonomic diversity, distinctness and variation of taxonomic distinctness were lower in the cultivated than in the natural site. PMID- 24232505 TI - Does the presence of secondary antiphospholipid syndrome in patients with systemic lupus erythematodes accelerate carotid arteries intima-media thickness changes? AB - Patients with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. The aim of our study was to evaluate the importance of secondary antiphospholipid presence (SAPS) in light of carotid artery intima-media thickness (CIMT) changes in SLE patients. Our study included 120 patients with SLE (46.02 +/- 13.16 years), 108 women and 12 men divided into two groups: 58 patients with SAPS and 62 SLE patients without SAPS taken as a control group. All patients underwent assessment of CIMT of right and left common carotid artery (CCA) and left and right internal carotid artery (ICA) by Doppler ultrasonography. In SAPS group, 48.3 % patients had significant changes of carotid arteries comparing to 16.1 % patients in control group (p = 0.008). Average CIMT values in left and right CCA and right ICA were significantly higher in SAPS group. No significant relationship between antiphospholipid antibody type and CIMT changes was established. Multivariate regression analysis revealed SAPS as a significant predictor of CIMT changes in SLE patients (p = 0.025). Presence of SAPS in SLE patients is associated with significant CIMT changes. Additional autoimmune burden leads to a need for a more aggressive education and prevention considering standard risk factors in this group of patients. PMID- 24232506 TI - The reactivity of CO2 on the MgO(100) surface. AB - We investigate the adsorption of CO2 over an MgO(001) terrace, as calculated using an embedded cluster method. We find adsorbed geometries for CO2 on the perfect surface with energies which differ appreciably from previous studies, and observe that it is polarization of the surface rather than the inclusion of electron correlation which leads to this discrepancy. Our results suggest that both monodentate and tridentate carbonate formation on the MgO(001) surface are favourable processes, with the monodentate structure being of lower energy. Adsorption of CO2 is found to be favourable at both F(0) and F(+) terrace sites, but not at F(2+). We also find that chemisorption at oxygen vacancy sites with a single localized electron (F(+)) could provide a route for the conversion of CO2 to other products, and that this system may be a useful model for other, more effective catalysts. PMID- 24232504 TI - Antiphospholipid syndrome nephropathy (APSN) in patients with lupus nephritis: a retrospective clinical and renal pathology study. AB - Data about clinical-laboratory features and outcome of antiphospholipid syndrome nephropathy (APSN) in the course of lupus nephritis (LN) are scarce. To determine prevalence, clinical correlations and outcome of APSN in patients with LN, retrospective analysis of renal specimens and review of medical records from 48 LN patients were performed. APSN was found in 12/48 (25 %) of LN. Positivity for lupus anticoagulant (LAC) and double antiphospholipids positivity [LAC plus anticardiolipin (aCL)] were significantly more frequent in APSN-LN (p = 0.02 and p = 0.01, respectively) than in LN, while single aCL positivity was not. Overt antiphospholipid syndrome appeared more frequent in patients with APSN-LN (p = 0.05). There were no statistically significant differences between APSN-LN and LN in the proportion of each World Health Organization class of LN (with the exception of a trend toward fewer Class III LN in APS-LN) and in the systemic lupus erythematosus (SLE) disease duration and severity. At the time of renal biopsy, patients with APSN-LN had median serum creatinine levels significantly higher than patients with LN [1.45 (0.6-6.6) vs. 1.00 (0.7-3.0), p = 0.02]. Double antiphospholipid positivity was the only variable significantly associated with APSN-LN at multivariate regression analysis (OR 8, 95 % CI 1.7-37, p = 0,008). APSN-LN and LN did not differ significantly as regards the rate of complete (25 vs. 19.4 %, p = 0.72) and partial treatment response (25 vs. 29 %, p = 0.82) at 6 months and the progression to end-stage renal disease after a median follow-up of 8.1 +/- 3.6 years (16.6 vs. 13.8 %, p = 0.82). APSN was demonstrated in a quart of LN, appeared to be independent from underlying LN class and SLE severity, and did not seem to confer a worse prognosis to LN. The findings of higher creatinine and more interstitial fibrosis in APSN should be confirmed in future prospective larger studies. PMID- 24232508 TI - A twin-free single-crystal Ag nanoplate plasmonic platform: hybridization of the optical nano-antenna and surface plasmon active surface. AB - Surface plasmons based on metallic nanostructures enable light manipulation beyond the optical diffraction limit. We have epitaxially synthesized twin-free single-crystal Ag nanoplates on SrTiO3 substrates. Unlike the nanoplates synthesized in a solution phase, these nanoplates have perfectly clean surfaces as well as a quite large size of tens of micrometers. As-synthesized defect-free single-crystal Ag nanoplates have an atomically flat surface and sides with well defined angles, allowing long distance propagation of surface plasmons and highly reliable plasmonic integration. By spatially separating receiving and transmitting antennas and plasmonically interfacing them, the signal quality of transmission/reception can be largely improved. Furthermore, by combining sub dimensional nanostructures onto the two-dimensional space effective hierarchical plasmonic nano-complexes can be built up. Theoretical simulations well reproduced unique experimental results of coupling between SPPs and free-space radiation by the nanoplate antenna sides, low-loss long-range SPP propagation, and tunneling or scattering of SPPs at a nano-gap as well as a nano-structure introduced on the nanoplate. The single-crystal Ag nanoplate will find superb applications in plasmonic nano-circuitry and lab-on-a-chip for biochemical sensing. PMID- 24232509 TI - Immediate breast reconstruction does not increase postmastectomy pain. AB - BACKGROUND: Postmastectomy pain syndrome (PMPS) is a recognized complication of breast surgery, with a reported prevalence of 20-52 %. We investigated whether patients having immediate reconstruction (IR) reported more long-term pain compared to those having mastectomy alone (MA). We also investigated treatment factors influencing PMPS. METHODS: In a single center, all patients who underwent MA or IR between January 2009 and June 2011 and attended for follow-up between February 2012 and July 2012 were identified. Patients were invited to complete two questionnaires, a pain intensity visual analog scale (VAS, scored 0 to 10) and the PainDetect screening tool for neuropathic pain. RESULTS: Of 318 patients due to attend, 272 (86 %) submitted complete questionnaires. Of these, 134 (49 %) women had IR (implant based n = 93, pedicled flaps n = 33, free flaps n = 8). The overall point prevalence pain was low, with 221 (81 %) reporting VAS current pain as zero. Only 8 (3 %) patients reported a VAS score above 4. Six (2 %) patients had a positive PainDetect score. The percentage of patients reporting VAS scores greater than zero and positive or borderline PainDetect scores was similar for MA and IR (VAS: 13 and 14 %, respectively; PainDetect: 6 and 11 %, respectively). Radiotherapy was the strongest predictor of neuropathic pain. CONCLUSIONS: In this cohort, the prevalence of PMPS was lower than historic reports. We find no evidence of increased overall pain intensity or chronic neuropathic pain after IR compared to MA despite additional tissue dissection and potential donor site morbidity. This adds support to the positive benefits of breast reconstruction. PMID- 24232507 TI - Neuregulin-1 overexpression and Trp53 haploinsufficiency cooperatively promote de novo malignant peripheral nerve sheath tumor pathogenesis. AB - Malignant peripheral nerve sheath tumors (MPNSTs) are Schwann cell-derived malignancies that arise from plexiform neurofibromas in patients with mutation of the neurofibromin 1 (NF1) gene. We have shown that the growth factor neuregulin-1 (NRG1) also contributes to human neurofibroma and MPNST pathogenesis and that outbred C57BL/6J * SJL/J transgenic mice overexpressing NRG1 in Schwann cells (P0 GGFbeta3 mice) recapitulate the process of neurofibroma-MPNST progression. However, it is unclear whether NRG1 acts predominantly within NF1-regulated signaling cascades or instead activates other essential cascades that cooperate with NF1 loss to promote tumorigenesis. We now report that tumorigenesis is suppressed in inbred P0-GGFbeta3 mice on a C57BL/6J background. To determine whether NRG1 overexpression interacts with reduced Nf1 or Trp53 gene dosage to "unmask" tumorigenesis in these animals, we followed cohorts of inbred P0 GGFbeta3;Nf1+/-, P0-GGFbeta3;Trp53+/- and control (P0-GGFbeta3, Nf1+/- and Trp53+/-) mice for 1 year. We found no reduction in survival or tumors in control and P0-GGFbeta3;Nf1+/- mice. In contrast, P0-GGFbeta3;Trp53+/- mice died on average at 226 days, with MPNSTs present in 95 % of these mice. MPNSTs in inbred P0-GGFbeta3;Trp53+/- mice arose de novo from micro-MPNSTs that uniformly develop intraganglionically. These micro-MPNSTs are of lower grade (WHO grade II-III) than the major MPNSTs (WHO grade III-IV); array comparative genomic hybridization showed that lower grade MPNSTs also had fewer genomic abnormalities. Thus, P0 GGFbeta3;Trp53+/- mice represent a novel model of low- to high-grade MPNST progression. We further conclude that NRG1 promotes peripheral nervous system neoplasia predominantly via its effects on the signaling cascades affected by Nf1 loss. PMID- 24232510 TI - Assessing prognostic significance of preoperative alpha-fetoprotein in hepatitis B-associated hepatocellular carcinoma: normal is not the new normal. AB - BACKGROUND: Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear. METHODS: Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. RESULTS: Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4-4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30-1.98), disease-free survival (HR = 1.26; 95 % CI 1.10-1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07-1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1-5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7-327,560.0 ng/mL) and Ishak stage 6 cirrhosis. CONCLUSIONS: Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC. PMID- 24232511 TI - Harmonic scalpel versus electrocautery dissection in modified radical mastectomy: a randomized controlled trial. AB - PURPOSE: To test the hypothesis that the use of a harmonic scalpel increases operative time but results in less estimated blood loss, postoperative pain, drainage volume, and duration of surgery, as well as fewer complications, such as flap necrosis, seroma, and surgical site infection (SSI), than electrocautery. METHODS: This parallel-group, single-institution blinded randomized controlled trial was conducted at the department of surgery of our institute between April 2010 and July 2011. Women undergoing modified radical mastectomy were randomly allocated to either harmonic dissection (n = 76) or electrocautery (n = 76). RESULTS: Both the groups were comparable for baseline variables with age of 50.5 +/- 12.2 and 48.5 +/- 14.5 years in the harmonic and electrocautery groups, respectively. Harmonic dissection yielded better outcomes compared to electrocautery with lower estimated blood loss (100 +/- 62 vs. 182 +/- 92, p < 0.001), less drain volume (631 +/- 275 ml vs. 1035 +/- 413 ml, p < 0.001), fewer drain days (12 +/- 3 vs. 17 +/- 4, p < 0.001), less seroma formation (21.3 vs. 33.3 %, p = 0.071), and less postoperative pain [median (interquartile range) 2 (2-2) vs. 3 (3-4), p < 0.001], whereas mean operative time (191 +/- 44 vs. 187 +/ 36 min, p = 0.49) and SSI (0 vs. 4 %, p = 0.122) did not differ. On multivariable Cox regression analysis, harmonic dissection was associated with lower risk of significant postoperative pain [adjusted relative risk 0.028 (95 % confidence interval (CI) 0.004-0.2)] and overall complications [adjusted relative risk 0.47, (95 % CI 0.26-0.86)]. On multiple linear regression, duration of drains in the harmonic dissection group was 4.5 days less than electrocautery (r2 = 0.28, beta = 11.8, p < 0.001). CONCLUSIONS: The harmonic scalpel significantly reduces postoperative discomfort and morbidity to the patient without increasing operating time. We thus recommend preferential use of harmonic dissection in modified radical mastectomy. (ClinicalTrials.gov NCT01587248). PMID- 24232512 TI - Budding and prosthecate bacteria from freshwater habitats of various trophic states. AB - Budding and prosthecate bacteria were enumerated in spring and summer by viable counting procedures in several freshwater habitats in Australia including oligotrophic lakes, a mesotrophic lake, and eutrophic ponds.Caulobacter spp. were the most numerous type encountered. They were present in the highest concentrations (exceeding 1000/ml) in the mesotrophic lake during the summer. Their proportion to total viable heterotrophic bacteria was also highest (35.1 to 37.7) in this habitat. From 17 to 330/mlCaulobacter spp. were counted in the eutrophic habitats where their proportion to total viable numbers was less than 1.0%. In the oligotrophic lakes they varied from 5 to 23/ml and comprised greater than 5% of the total viable count.Hyphomicrobium- like bacteria were also numerous in the mesotrophic lake and in one oligotrophic lake during the summer sampling period.Ancalomicrobium spp. occurred in high concentrations (130/ml) in the mesotrophic lake. Budding bacteria of thePlanctomyces-Pasteuria group were most numerous in the eutrophic habitats where as many as 240/ml were counted; their proportion to total heterotrophs remained relatively constant regardless of trophic state, however. A similar pattern was observed withProsthecobacter spp. PMID- 24232513 TI - A method for the analysis of acetate turnover in a coastal marine sediment. AB - The concentrations of volatile fatty acids were measured in the pore water of sediment from the Limfjorden, Denmark. The pore water was freeze-dried and the acids, which were redissolved in formic acid, were analyzed by gas chromatography on a Carbopack column. The limit of detection was 0.1 MUmol l(-1) pore water. The concentration ranges (MUmol l(-1) pore water) were as follows: 0.1 to 6.0 for acetate; <0.1 to 0.6 for propionate, and <0.1 to 0.5 for butyrate. The rate constants for the disappearance of injected tracer concentrations of U-(14)C acetate were measured at 2 cm depth intervals in sediment strata (0 to 10 cm). The rate constant for acetate turnover at 4 to 6 cm depth did not vary greatly with season, 2.1 h(-1), SD 0.6 for 7 values. In spring, the rate constants were highest in the 0 to 2 cm stratum and decreased with sediment depth. The calculated rates for acetate turnover of 7.2 mmol m(-2) day(-1) for early spring (2 degrees C) and of 19.6 mmol m(-2) day(-1) for late autumn (7 degrees C) were higher than would be expected from published values for carbon oxidation by sulfate in these sediments. PMID- 24232514 TI - Structure, diversity, and catabolic potentialities of aerobic heterotrophic bacterial populations associated with continuous cultures of natural marine phytoplankton. AB - Variations of structure (probable taxonomic generic groups; ecological profiles), diversity (Shannon index, -H), and average catabolic potentialities (strain's average exoenzyme equipment, EAI; average carbonaceous compound utilization, UAI) of bacterial populations during two experimental phytoplankton blooms are described and show a certain overall unity. Oligotrophic conditions are characterized by high diversity levels (-H from 3.60 to 4) and moderate catabolic potentialities (EAI and UAI close to 40%). During phytoplankton exponential growth phase bacteria show an EAI stability, but there is an increase of UAI with maximal values at the beginning of chlorophyll plateau (52-57%) and higher values of diversity (-H greater than 4). Phytoplankton mortalities appear to cause an EAI increase and a decrease of both UAI and -H (1.50 to 2). Vibrio-like organisms seem to be closely related to this period.In spite of these similar patterns, many differences appear between both experiments from a taxonomic point of view, the autumnal population being more diversified than the spring one.The results obtained show the value of simultaneous analysis of these different aspects and of this ecological methodology allowing spatial or temporal comparisons. PMID- 24232515 TI - Slope of the Monod equation as an indicator of advantage in nutrient competition. AB - Apparently by analogy with enzyme kinetics, the half-saturation value (K) for nutrient uptake or growth has frequently been overemphasized in discussions of competition, and the role of maximum rates (Rm) has not been given sufficient emphasis. The ratio Rm/K, which is the slope of the Monod equation at lowest substrate concentration, offers a simple way of emphasizing both factors. Several examples from the literature are cited to show that this ratio better reflects rates at lowest concentrations, and therefore competitive position in the process being considered, than do K values alone. PMID- 24232516 TI - Uptake of hydrocarbons by the marine diatomCyclotella cryptica. AB - The accumulation of exogenous hydrocarbons by the marine diatomCyclotella cryptica grown in culture has been studied using gas chromatography. Exposure of the alga to paraffins for 10 days results in accumulation of n-alkanes having between C13 and C16 carbon atoms. The C16 level in the accumulated fraction is twice as high as that in the original oil. PMID- 24232517 TI - Effect of long-term lead exposure on the seawater and sediment bacteria from heterogeneous continuous flow cultures. AB - Lead-influenced changes of the composition of seawater and sediment bacteria were studied in two flow cultures run with lead-contaminated artificial seawater (1 mg Pb(2+)1(-1)) and one control culture. During the experiment viable counts of physiological groups of bacteria from the control culture were not significantly different from that of the lead-contaminated cultures. Lead tolerance of seawater and sediment bacteria strains was investigated. Comparisons of growth yields showed that lead tolerance of seawater and sediment bacteria was lost again if the bacteria were cultivated in a medium without lead. Lead tolerance could not be demonstrated for the sediment bacteria of one lead-contaminated culture. Heterotrophic uptake measurements with radioactive glucose indicated that seawater bacteria from the lead-contaminated cultures became adapted to lead pollution. The sediment bacteria, however, did not reveal lead tolerance by this method. Fluctuations in lead content of the sediment as well as of the overlying seawater gave indications of adsorption-desorption processes between seawater and sediment. Lead was not homogeneously distributed at the sediment surface. PMID- 24232518 TI - Fate of ciliates in the earthworm gut: An in vitro study. AB - The behavior of the ciliateColpidium campylum was unaffected by exposure in vitro to high concentrations of pharyngeal and hindgut fluids from the earthwormLumbricus terrestris, but movement became abnormal and ceased in concentrations of midgut fluid as low as 1.5%. On mixingC. campylum culture with an equal volume of midgut fluid, which often contained resident astomatous ciliates, the.C. campylum cells were immediately immobilized and frequently disintegrated, while the astomatous ciliates continued to behave normally. Possible causes of the hostility of the midgut environment, and implications for earthworm nutrition, are discussed. PMID- 24232519 TI - Influence of five pyrethroid insecticides on microbial populations and activities in soil. AB - Laboratory tests were conducted to determine the effects of five pyrethroid insecticides-permethrin (FMC 33297) [3-phenoxybenzyl (+/-)-3-(2,2-dichlorovinyl) 2,2-dimethylcyclopropanecarboxylate]; FMC 45498 [(S)-alpha-cyano-3-phenoxybenzyl (R)-cis-2-(2,2-dibromovinyl)-3,3-dimethylcyclopropanecarboxylate]; Shell WL 41706 [(+/-)-alpha-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropane-carboxylate]; Shell WL 43467 [(+/-)-alpha-cyano-3-phenoxy benzyl (+/-)-cis,trans-2-(2,2 dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate]; and Shell WL 43775 [(+/-) alpha-cyano-3-phenoxybenzyl (+/-)-2-(4-chlorophenyl)-3-methylbutyrate]-at 0.5 and 5MUg/g on microbial populations and activities in a sandy loam. The insecticides had antimicrobial activity in early stages of incubation. The populations recovered after 2 to 4 weeks and stimulatory effects on populations were also observed in later stages. No inhibition of acetylene (C2H2) reduction was evident with any of the insecticides. However, WL 43467 at both concentrations and permethrin and WL 41706 at 5 MUg/g increased nitrification after 4 weeks. Soil microbial respiration, as indicated by oxygen consumption, increased with increasing concentration of insecticides, suggesting the possibility of microbial degradation of the insecticides. Dehydrogenase activity showed that none of the insecticides inhibited formazan (2,3,5-triphenyltetrazolium formazan) formation, whereas urease activity was stimulated in most cases. The studies indicated that some of the pyrethroid insecticides may exert transient effects on populations and activities of the microflora in a sandy loam, but these were short-lived and minor in nature. PMID- 24232520 TI - Effect of several environmental parameters on carbon metabolism in histosols. AB - High specific activity(14)C-labeled glucose, succinate, acetate, salicylate, and amino acids were used to examine carbon metabolism by the microbial community of Pahokee muck (aLithic medisaprist), a drained, cultivated soil of the Florida Everglades. Variations in carbon oxidation were observed from the end of the wet season through the dry season in a fallow (bare) field. Evolution of(14)CO2 varied with the substrate added and time. Calculation of(14)CO2 evolution for each substrate as a proportion of total respiration of the microbial community which was measured by succinate oxidation (relative oxidation) allowed for determination of the proportion of metabolic activity contributed by the oxidation of each carbon source. Except for the May sample when an approximate 30% decline in relative salicylate oxidation activity was observed, the proportion of total catabolic activity contributed by salicylate oxidation and acetate degradation was constant with time. Relative oxidation of glucose and amino acids ranged from 0.12 to 0.52 and 0.10 to 0.23, respectively. At two times during the dry season, the effect of depth of soil and crop on the carbon oxidation was examined. Relative acetate and amino acid oxidation were constant with depth whereas statistically significant variation was observed in glucose and salicylate oxidation. Generally, with the latter substrates, the activity declined with increased soil depth. Greatest effect of crop on these metabolic activities was noted with oxidation of salicylate in soils from a St. Augustinegrass [Stenatophrum secundatum (Walt.) Kuntz] pasture. In these soils, oxidation of salicylate was nearly double that of the fallow field or of soil planted with sugarcane (Saccharum sp.). PMID- 24232521 TI - Is pi halogen bonding or lone pair...pi interaction formed between borazine and some halogenated compounds? AB - Borazine, "inorganic benzene", exhibits some different properties from benzene although both of them are isostructural and isoelectronic. It was known that benzene is favorable to form halogen bonds with halogenated molecules. However, borazine more easily forms lone pair-pi interactions with halogenated molecules, but for stronger halogen donors it can also form halogen bonds. The halogen bonds formed by borazine are stronger than the corresponding lone pair-pi interactions. It was found that the pair-pi interactions can be changed into halogen bonds with the increase of interaction strength. The dispersion energy plays a main role in stabilizing the weakly bonded complexes, while the electrostatic energy is dominant in the strongly bonded complexes. This is different from the nature of the respective benzene complexes. PMID- 24232522 TI - Methodologies for estimating the sample size required for genetic conservation of outbreeding crops. AB - The main purpose of germplasm banks is to preserve the genetic variability existing in crop species. The effectiveness of the regeneration of collections stored in gene banks is affected by factors such as sample size, random genetic drift, and seed viability. The objective of this paper is to review probability models and population genetics theory to determine the choice of sample size used for seed regeneration. A number of conclusions can be drawn from the results. First, the size of the sample depends largely on the frequency of the least common allele or genotype. Genotypes or alleles occurring at frequencies of more than 10% can be preserved with a sample size of 40 individuals. A sample size of 100 individuals will preserve genotypes (alleles) that occur at frequencies of 5%. If the frequency of rare genotypes (alleles) drops below 5%, larger sample sizes are required. A second conclusion is that for two, three, and four alleles per locus the sample size required to include a copy of each allele depends more on the frequency of the rare allele or alleles than on the number. Samples of 300 to 400 are required to preserve alleles that are present at a frequency of 1%. Third, if seed is bulked, the expected number of parents involved in any sample drawn from the bulk will be less than the number of parents included in the bulk. Fourth, to maintain a rate of breeding (F) of 1 %, the effective population size (N e) should be at least 150 for three alleles, and 300 for four alleles. Fifth, equalizing the reproductive output of each family to two progeny doubles the effective size of the population. Based on the results presented here, a practical option is considered for regenerating maize seed in a program constrained by limited funds. PMID- 24232523 TI - Production and cytogenetics of Triticum aestivum L. hybrids with some rhizomatous Agropyron species. AB - Intergeneric hybrids between Triticum aestivum L. and conventional rhizomatous Agropyron species were produced in variable frequencies. They were recovered in high percentage frequencies for T. aestivum cultivars with A. acutum (14.6%), A. intermedium (48.0%), A. pulcherrimum (53.3%), and A. trichophorum (46.6%). The crossability percentages with the highly crossable cultivar 'Chinese Spring' for these Agropyron species accessions were 33.12%, 65.0%, 53.3%, and 65.4%, respectively. Autosyndetic associations of two of their three genomes gave mean meiotic chromosome association data of 17.0 I (univalents) +1.53 II (ring bivalents) + 7.04 II (rod bivalents) +1.43 III (trivalents) +0.05 IV (quadrivalents) +0.01 IV (pentavalents) for A. acutum and of 21.8 I + 1.56 II (rings) +7.22 II (rods) +0.84 III + 0.04 IV for A. intermedium. Chromosome pairing at metaphase I was comparatively lower for A. pulcherrimum (34.4 I + 0.2 II (rings) +3.4 II (rods) +0.14 III) and A. trichophorum (36.7 I + 0.35 II (rings) +2.26 II (rods) + 0.04 III) hybrids with T. aestivum. Hybrids of wheat with A. campestre and A. repens were obtained in low frequency. Direct crossing did not permit T. aestivum/ A. desertorum hybridization. However, by utilizing the 2n=10x=70 A. repens/A. desertorum amphiploid as the pollen source, hybridization with T. aestivum did indeed occur. Aneuploidy was prevalent in this hybrid combination while all other hybrid combinations were apparently normal. PMID- 24232524 TI - Identification of new mitochondrial genome organizations in wheat plants regenerated from somatic tissue cultures. AB - Plants have been regenerated from short-and long-term in vitro somatic tissue cultures made from immature embryos of the hexaploid wheat cultivar "Chinese Spring". The mitochondrial genome organization of each regenerated plantlet was studied, after one selfing, by probing Sal I-restricted total DNA with cloned Sal I fragments of wheat mitochondrial DNA derived from a segment of the genome, which displays marked structural changes in response to in vitro culture. Short term in vitro cultures give rise to regenerated plants whose mitochondrial genome organization is either close to that of the parental cultivar or to that of embryogenic callus cultures, except for a single plant which has an organization resembling that of short-term non-embryogenic cultures. In contrast, all but one of the plants regenerated from long-term cultures exhibited a mitochondrial genome organization similar to that of long-term nonembryogenic cultures. In addition, extra labelled bands were detected in some of the regenerated plants with two of the probes used. These results emphasize the importance of the duration of the in vitro step preceding the regeneration process: the longer it is, the higher the probability is of obtaining mitochondrial DNA variability in regenerated plants. Furthermore, since increasing the duration of the in vitro stetp results in the production of regenerated plants with a mitochondrial genome organization resembling that of non-embryogenic tissue cultures, the question is thus raised as to whether regeneration from long-term cultures is suitable for use in plant breeding. PMID- 24232525 TI - Segregation for endosperm lysine in F2, F 3 and F 4 progeny from a cross of in vitro-selected and unselected cultivar of rice. AB - Lysine is a limiting amino acid for optimal nutritional quality in rice grain. In vitro selections using inhibitory levels of lysine plus threonine or s aminoethylcysteine allow the predictable recovery of variants with elevated levels of lysine and protein. These methods may generate useful starting germplasm for plant breeders. This study was conducted to define the genetics of lysine mutants in progeny from crosses of mutants derived from cells cultured in vitro in the presence of inhibitory levels of lysine plus threonine and s-(2 aminoethyl)-cysteine. In vitro selections produce a wide range of mutants, including endosperm mutants with elevated lysine and protein levels as well as mutants for high and low seed weights. Mutants were analyzed for lysine content by the endosperm half-seed method in which the halves without the embryo were ground and acid hydrolyzed for amino acid determinations. The halves with the embryos were preserved for later germination. In two different F2 populations derived from a cross of a selected mutant x M-101, a parental marker, there was an inverse relationship between seed weight and percent lysine in endosperm protein (R(2) 0.52 and 0.56). The F2 segregation patterns show that elevated lysine is inherited as a recessive gene and that increased lysine is correlated with decreased seed size. F3 and F4 data provide evidence for the transmission of high lysine genes to advanced germplasm in rice. This work supports our earlier conclusions that high lysine phenotypes can be recovered predictably from in vitro selections. The elevated lysine phenotypes are frequently, but not exclusively, associated with opaque seed. Some segregants from crosses produced increased lysine in plants with near normal seed weight and good fertility. PMID- 24232526 TI - Biochemical and cytological characterization of wheat/Aegilops ventricosa addition and transfer lines carrying chromosome 4M(V.). AB - The gene encoding a variant of alcohol dehydrogenase, Adh-MU, has been found to be associated with the chromosome of the M(v) genome which is present in type 9 wheat/Aegilops ventricosa addition line, to which the genes for protein CM-4 and for a phosphatase variant, Aph-v, had been previously assigned. Transfer line H 93-33, which has 42 chromosomes and has been derived from the cross (Triticum turgidum x Ae. ventricosa) x T. aestivum, carries genes encoding all three biochemical markers. Linkage between these genes has been demonstrated by analysis of individual kernels of the F2 (H-93-33 x T. aestivum cv. "Almatense" H 10-15). A study of the hybrids of line H-93-33 with T. aestivum H-10-15 and with the 4DS ditelosomic line has confirmed that, as suspected, the linkage group corresponds to chromosome 4M(v) from Ae. ventricosa. Additionally, it has been found that the previously reported resistance of line H-93-33 to powdery mildew (Erysiphe graminis) is also linked to the biochemical markers; this indicates that either the gene responsible for it is different from that in lines H-93-8 and H-93-35, or that a translocation between two different M(v) chromosomes has occurred in line H-93-33. PMID- 24232527 TI - Asymmetric somatic hybrids of Brassica: partial transfer of B. campestris genome into B. oleracea by cell fusion. AB - To examine the possibility of producing asymmetric somatic hybrids of Brassica having a complete genome of one species and a part of the other, we fused inactivated B. oleracea protoplasts with X-irradiated B. campestris protoplasts. The plants obtained were studied with regard to their morphology, isozymes and chromosomes. The morphology of the hybrids was similar to B. oleracea in 9 out of 22 hybrids studied and the rest showed the intermediate phenotype of the parents. Analysis of three isozymes, leucine aminopeptidase, acid phosphatase and esterase indicated that ten hybrids lost B. campestris-specific bands in one or more of the three isozymes examined. The chromosome analysis showed that 90% of the hybrids were aneuploids. In addition, abnormal chromosomes were often found in root tip cells. These results suggested that the hybrids obtained were asymmetric in nature and resulted from elimination of B. campestris chromosomes by X-ray irradiation. PMID- 24232528 TI - Methods for the study of cytoplasmic effects on quantitative traits. AB - The methods used to study cytoplasmic effects in quantitative traits often do not measure quantitative genetic parameters, while those that do are either complicated or do not take into account situations where the expression of cytoplasmic effects does not persist, but decreases in advanced generations. We present two simple models that take cytoplasmic effects and the quantitative genetic parameters into account. One of the models (A) is for cases where cytoplasmic effects remain constant through successive generations, and the second model (B) is for traits where cytoplasm-genotype interactions are present. This model also takes into account the decreasing persistence of cytoplasmic effects with advancing generations, which is often reported in the literature. PMID- 24232529 TI - Genetic characterization of a mutation that enhances paraquat tolerance in the fern Ceratopteris richardii. AB - Three nuclear mutations that affect tolerance to the herbicide paraquat have been selected in the fern Ceratopteris richardii. Two of the mutations, pq2 and pq45 are allelic and confer low and moderate tolerance, respectively. A third mutation, pqa6, is not linked to the other two and significantly enhances the level of tolerance when in combination with either pq2 or pq45. The pqa6 mutation does not independently confer tolerance in the absence of the other mutations. PMID- 24232530 TI - Establishment of a system of high-frequency embryogenesis from long-term cell suspension cultures of rice (Oryza sativa L.). AB - Suspension cultures which maintained embryogenic potency for more than 18 months were established from excised immature embryos of rice (Oryza sativa L. cv. Konansou). The cultures were subcultured every three days in N6 medium supplemented with proline (10 mM), casein hydrolysate (300 mg/l), sucrose (30 g/l) and 2,4-D (1 mg/l). The frequency of embryogenesis from the embryogenetic suspension cultures reached about 90% when cell clusters (about 1 mm in diameter) were transferred to a solid medium which consisted of N6 medium, NAA (1 mg/l), kinetin (5 mg/l), sucrose (30 g/l) and Gelrite (2 g/l). When smaller clusters of cells (approximately 200-400 MUm in diameter) were transferred to a liquid medium which consisted of salts of N6 medium diluted with an equal volume of water plus sucrose (45 g/l), NAA (0.01 mg/l) and 4-PU (0.1 mg/l) at a cell density of 13 clusters/ml in 2 ml of medium, somatic embryogenesis was initated at high frequency (about 50%). Morphological evidence is provided to demonstrate that the regeneration occurred via embryogenesis. This is the first report of high frequency embryogenesis in suspension cultures of rice cells. PMID- 24232531 TI - Paternal inheritance of chloroplast DNA and maternal inheritance of mitochondrial DNA in loblolly pine. AB - The inheritance of organelle DNAs in loblolly pine was studied by using restriction fragment length polymorphisms. Chloroplast DNA from loblolly pine is paternally inherited in pitch pine x loblolly pine hybrids. Mitochondrial DNA is maternally inherited in loblolly pine crosses. The uniparental inheritance of organelle genomes from opposite sexes within the same plant appears to be unique among those higher plants that have been tested and indicates that loblolly pine, and possibly other conifers, must have special mechanisms for organelle exclusion or degradation or both. This genetic system creates an exceptional opportunity for the study of maternal and paternal genetic lineages within a single species. PMID- 24232532 TI - Linkages among zein genes determined by isoelectric focusing. AB - Genetic control of the major zein polypeptides in maize (Zea mays L.) was studied by isoelectric focusing (IEF) in agarose. Linkage relationships were determined by making a number of crosses, then determining the expression of zein polypeptides in backcross seeds. Chromosome linkages were determined by using the markers sugary-1 (for chromosome 4), yellow-8, and a waxy 7-9 translocation (for chromosome 7). Nine zeins were in one linkage group on chromosome 4, six in another linkage group on chromosome 4, and four zeins were in one linkage group on chromosome 7. Some IEF single bands consisted of at least two polypeptides, which were detected by subsequent sodium dodecyl sulfate polyacrylamide gel electrophoresis, by aberrant ratios in backcrosses, or by differing recombination percentages. One zein occurred only in homozygous sugary-1 seeds. Three sets of closely-linked zeins were noted that occurred together almost exclusively in certain inbreds. PMID- 24232533 TI - Evaluation of soybean resistance to Phialophora gregata culture filtrate in tissue culture. AB - Resistance to the fungal pathogen, Phialophora gregata (Allington and Chamberlain) W. Gams, the cause of brown stem rot (BSR) in soybean [Glycine max (L.) Merr.], is an important trait for cultivars grown in the northern USA. A novel tissue culture method was developed where ten soybean cultivars were differentiated on the ability of their excised cotyledons to remain green and initiate callus in a tissue culture medium containing P. gregata culture filtrate. Cultivar BSR classifications by the cotyledon method corresponded to greenhouse root-dip assay classifications in 80%, 100%, and 90% of the three P. gregata isolate treatments. Another method, employing pieces of somatic callus exposed to the culture filtrate, had a 70% average correspondence to the greenhouse results. Physiologic specialization was demonstrated in parallel in vivo/in vitro assays for the first time. These data suggest that the cotyledon method would accurately identify soybean lines resistant to certain aberrant or wild-type P. gregata isolates. PMID- 24232534 TI - Ibf-1 (Iodine binding factor), a highly variable marker system in the Triticeae. AB - Isoelectric focusing of extracts from the endosperm of mature grains of hexaploid wheat and related species was used to study the genetic control of 'Iodine binding factor' (IBF). Ten IBF bands were present in "Chinese Spring" ("CS") and analysis of the nullisomictetrasomic and ditelosomic lines of "CS" showed nine of them to be controlled by genes on the long arms of the homoeologous group 5 chromosomes. Five alleles were detected at Ibf-A1 locus, four at Ibf-B1 and four at Ibf-D1 among a sample of 46 wheat genotypes. Homoeoloci were found on chromosome 5R of Secale cereale, 5E of Agropyron elongatum, 5U of Aegilops umbellulata, 5Ag(i) of Agropyron intermedium, 5S(1) and 4S(1) of Aegilops sharonensis and 4H of Hordeum vulgare. PMID- 24232535 TI - Chromosomal location of resistance to barley yellow mosaic virus in German winter barley identified by trisomic analysis. AB - In order to localize a gene for resistance to Barley Yellow Mosaic Virus (BaYMV) of German resistant varieties, cvs. 'Ogra' and 'Sonate' were crossed to a complete trisomic (2n=2x+1=15) set of 'Shin Ebisu 16'. Tests for resistance in F2 strongly support the conclusion that the German gene for resistance to BaYMV is located on barley chromosome 3. PMID- 24232536 TI - Cross prediction in a potato breeding programme by evaluation of parental material. AB - It is shown that it is possible to obtain an indication of the parental value of heterozygous cultivars of potatoes for the characters breeders' preference, total tuber weight, mean tuber weight and number of tubers. Three methods of predicting the characteristics of progeny produced from particular parental cultivars were examined, namely: univariate cross prediction (based on mean and variance), mid parent values and mid-self values. All provided some indication of which crosses would give superior progeny, but univariate cross prediction gave rankings which correlated most highly with observed performance in the second clonal year for the characters breeders' preference and total tuber weight. Interestingly, mid self values gave the best predictions in the case of mean tuber weight and number of tubers. It is suggested that such predictions of 'parental value', especially when based on univariate cross prediction at the seedling stage, are worth carrying out in practical breeding programmes. PMID- 24232537 TI - Heterosis in crosses between lines of Drosophila melanogaster selected for adaptation to different environments. AB - Experiments were designed to examine whether heterosis would occur in crosses of Drosophila melanogaster populations adapted to 18 degrees C or 28 degrees C environments. Crosses were examined in parental environments, an intermediate environment (23 degrees C) and a mixed environment (alternating 18 degrees /28 degrees C). Parental populations did not show divergence for larval viability, cold shock or high temperature mortalities when tested in a common environment. However, the 28 degrees C population was less fecund than the 18 degrees C population, but had higher larval competitive ability and higher adult longevity. Heterosis for viability, cold shock mortality and high temperature mortality occurred in crosses between a population adapted to 18 degrees C and another adapted to 28 degrees C, but not in crosses between two populations adapted to the same temperature. The results suggest that, in the absence of drift, heterosis is expected in crosses between lines or populations with different histories of selection but not between lines with the same selection histories. PMID- 24232538 TI - Genetic control of seed weight in flax (Linum usitatissimum) and possible implications. AB - Mean seed weight data were obtained from the F1 and F2 of a six-by-six diallel cross with flax (Linum usita-tissimum L.). Pronounced reciprocal differences appeared in the F1, but had largely disappeared by the F2. The genetic control of mean seed weight was examined using two types of analysis of variance. The models underlying both analyses were fitted to the data by matrix methods supplying weighted least-squares estimates of the parameters in the models. Weights, the use of which dealt with the problem of variation in the reliability of means, were the reciprocals of the variances of individual cell (cross/self) means in the diallel data table. Elimination of redundant parameters supplied the minimum adequate models for each analysis type. Dominance was apparently masked by the large transient maternal effects in the F1, but surfaced in the F2, where dominance was towards larger mean seed weight. This may be coupled with findings elsewhere of possible advantages for larger seed weights to speculate on a role in preserving infrequent hybrid progeny among inbreeding (flax) species. Maternal effects producing larger seed size, plus dominance with the same result might be valuable, in conjunction with growth and competitive advantages conferred by larger seed, in preventing early elimination of rare hybrids. PMID- 24232539 TI - Genetic variability between two breeds based on restriction fragment length polymorphisms (RFLPs) of major histocompatibility complex class I genes in the pig. AB - Restriction fragment length polymorphism analyses of SLA class I genes were performed on 55 Duroc and 24 Hampshire boars from the 1986-87 national performance tests of each breed. Few boars were inbred. Southern blotting and hybridization procedures were performed on genomic DNA isolated from white blood cells by using Pvu II, Bam HI, and Eco RI endonucleases and a swine MHC class I probe. Genetic variability within and between the two breeds was estimated in terms of nucleotide diversity, by using a mathematical analysis based on the different RFLP patterns. The nucleotide diversity calculated within each breed was less than that between the two breeds. The results from the nucleotide diversity analysis suggested that genetic variability was greater in the Duroc breed than in the Hampshire breed. A relatively high level of genetic variability was shown in the class I major histocompatibility complex genes in the pig. PMID- 24232540 TI - Diversity pattern in Sesamum mutants selected for a semi-arid cropping system. AB - Due to the complex requirements of moisture stress, substantial genetic diversity with a wide array of character combinations and effective simultaneous selection for several variables is necessary for improving the productivity and adaptation of a component crop in order for it to fit into a cropping system under semi-arid tropical conditions. Sesamum indicum L. is grown in Venezuela after rice/sorghum/or maize under such conditions. A mutation breeding program was undertaken using six locally adapted varieties to develop genotypes suitable for the above system. The diversity pattern for nine variables was assessed by multivariate analysis in 301 M4 progenies. Analysis of the characteristic roots and principal components in three methods of selection, i.e., M2 bulks (A), individual plant selection throughout (B), and selection in M3 for single variable (C), revealed differences in the pattern of variation between varieties, selection methods, and varieties x methods interactions. Method B was superior to the others and gave 17 of the 21 best M5 progenies. 'Piritu' and 'CF' varieties yielded the most productive progenies in M5 and M6. Diversity was large and selection was effective for such developmental traits as earliness and synchrony, combined with multiple disease resistance, which could be related to their importance by multivariate analyses. Considerable differences in the variety of character combinations among the high yielding. M5 progenies of 'CF' and 'Piritu' suggested possible further yield improvement. The superior response of 'Piritu' and 'CF' over other varieties in yield and adaptation was due to major changes in plant type and character associations. Multilocation testing of M5 generations revealed that the mutant progenies had a 40%-100% yield superiority over the parents; this was combined with earliness, synchrony, and multiple disease resistance, and was confirmed in the M6 generation grown on a commercial scale. This study showed that multivariate analysis is an effective tool for assessing diversity patterns, choice of appropriate variety, and selection methodology in order to make rapid progress in meeting the complex requirements of semi-arid cropping systems. PMID- 24232541 TI - Distribution of genetic variability in a durum wheat world collection. AB - A durum wheat world collection of 349 entries has been used to study the amount and distribution of genetic variability based on isoenzymatic characters involving a minimum of 13 loci. Genetic variability has been studied in a hierarchical fashion: between origins and within origins, further divided into between entries per origin and within entries. Factorial analysis of correspondences and chi-square distance were the basic statistical tools. The effect of domestication is deduced by comparing isozymic frequencies between wild emmer and durum wheat. It involves changes in frequencies mainly towards the accumulation of "null" alleles. The richest origins of genetic variation for durum wheat were Iran, Mexico, Ethiopia, Egypt and Afghanistan. Generally, between-entry variability was larger than the withinentry component. Exceptions were the accessions from Mexico, Greece, Argentina and Cyprus. The relationships between origins were greatly affected by their within-variability, the logic in the grouping is mostly along geographical or political lines. Egypt might be considered a microcenter of diversity for durum wheat within the Mediterranean center, although it is certainly related to Ethiopia (included in the Abisinic center). Mexico has become a new microcenter of diversity, quite likely man-made, and is distant from other centers of durum wheat diversity as far as gene frequency is concerned. PMID- 24232542 TI - Monoparametric models of flow cytometric karyotypes with spreadsheet software. AB - Theoretical flow karyotypes from both plant and mammalian species have been simply modelled using computer spreadsheet software. The models are based upon published values of relative DNA content or relative lengths of each of the chromosomes. From such data, the histograms of chromosome distribution have been simulated for both linear and logarithmic modules of a flow cytometer, and as a function of the coefficient of variation. Simulated and experimental histograms are compard for Nicotiana plumbaginifolia. This readily accessible exercise facilitates the planning and execution of flow cytometric analysis and sorting of chromosomes. PMID- 24232543 TI - Analysis of factors affecting containment with extracted partial enclosures using computational fluid dynamics. AB - The Health and Safety Executive's (HSE's) COSHH Essentials (HSE, 2002, COSHH Essentials: easy steps to control chemicals HSG193. 2nd edn. ISBN 0 71762737 3. Available at http://www.coshh-essentials.org.uk. Accessed 30 October 2013) provides guidance on identifying the approaches required to control exposure to chemicals in the workplace. The control strategies proposed in COSHH Essentials are grouped into four control approaches: general ventilation, engineering control, containment, or to seek specialist advice. We report the use of experimental measurements and computational fluid dynamics (CFD) modelling to examine the performance of an engineering control approach and a containment control approach. The engineering control approach simulated was an extracted partial enclosure, based on the COSHH Essentials G200, for which simulations were compared with data from experiments. The containment approach simulated was of drum filling (in an extracted partial enclosure), based on the COSHH Essentials G305. The influence of the following factors on containment was examined: face velocity, size and location of face opening, and movement and ventilation flows. CFD predictions of the engineering control approach agreed well with the majority of the experimental measurements demonstrating confidence in the modelling approach used. The results show that the velocity distribution at the face of the enclosure is not uniform and the location and size of the opening are significant factors affecting the flow field and hence the containment performance. The simulations of drum filling show the effect on containment of the movement of a drum through the face of an enclosure. Analysis of containment performance, using a tracer, showed that containment was affected by the interaction between the ventilation flow direction and drum movement and spacing. Validated CFD simulations are shown to be a useful tool for gaining insight into the flows in control strategies for exposure control and to aid the interpretation of experimental measurements. The results support the assumption in COSHH Essentials that the use of 'containment' as a control approach is capable of achieving a 100 fold reduction in potential exposure. Novel CFD modelling techniques have been used to create controlled containment scenarios, improve understanding of the flow behaviour in the scenarios, and provide information that may aid future containment design. PMID- 24232544 TI - Ultrastructure, plasmodesmatal frequency, and solute concentration in green areas of variegated Coleus blumei Benth. leaves. AB - The photosynthetic tissue of green portions of variegated Coleus blumei leaves consists primarily of palisade and spongy parenchyma cells as well as bundle sheath cells. The moderate numbers of plasmodesmata connecting these cells may be sufficient to provide a symplastic pathway for assimilates moving toward the minor veins. The minor veins, however, are unusual in having two sets of phloem loading cells which have little symplastic continuity with one another: one consisting of large, peripherally located intermediary cells, and a second set made up of smaller, usually more internal companion cells, both sets having their associated sieve-tube members. The intermediary cells are connected to vascular parenchyma and bundle-sheath cells by unique branched plasmodesmata which are particularly abundant at the bundle-sheath interface. In addition, numerous plasmodesmata-pore connections occur between the intermediary cells and their associated sieve-tube members. Neither the intermediary cells nor their sieve tube members plasmolyze when treated with 1.4 M mannitol, whereas mesophyll and vascular-parenchyma cells plasmolyze at 0.5 M and bundle-sheath cells at 0.6 M mannitol. By contrast, the companion cells and their associated sieve-tube members are symplastically isolated from the bundle-sheath cells and the sieve tube-intermediary-cell complexes, and share few plasmodesmata with the vascular parenchyma cells. Moreover, the companion cells plasmolyze at 1.1 M mannitol and their sieve tubes at 1.3 M. The intermediary-cell-sieve-tube complex thus appears to be structurally equipped to load assimilates entirely via the symplast, while the sieve-tube-companion-cell complex is probably loaded from the apoplast. PMID- 24232545 TI - The plasma membrane of young Chara internodal cells revealed by rapid freezing. AB - Young elongating internodal cells of Chara globularis var. capillacea (Thuill.) Zanev. were rapidly frozen and freze-fractured in order to observed transient events occurring within the plasma membrane. Several structures have been observed. Relatively small depressions, varying in depth, are prolific and scattered at random over the plasma membrane. Charasomes and clusters of particle rosettes are common. Arrays of intramembrane particle lines are a characteristic feature of the internodal cell plasma membrane. The charasomes and the arrays of particle lines occupy a considerable proportion of the plasma membrane. In these young cells, substantial movement must take place across this membrane and its basic structure must fluctuate accordingly. The innumerable small depressions may represent pinocytotic and secretory processes. The array of intramembrane particle lines may represent stages in fusion between the membranes of vesicles within the cytoplasm and the plasma membrane. The technique of ultra-rapid freezing allows these events and their intermediate stages to be visualised; some features of the membrane may only be seen by this method. PMID- 24232546 TI - Light-induced changes in the distribution of the 36000-Mr polypeptide of NADPH protochlorophyllide oxidoreductase within different cellular compartments of barley (Hordeum vulgare L.) : I. Localization by immunoblotting in isolated plastids and total leaf extracts. AB - Changes in the relative content of NADPH-protochlorophyllide oxidoreductase during the light-induced greening of barley plants were measured both in the total leaf extract as well as in intact and broken plastids. The enzyme protein was identified by its apparent molecular weight and its immunological crossreactivity with an antiserum directed against the NADPH-protochlorophyllide oxidoreductase. The monospecificity of the antiserum was tested by two different criteria: i. The antiserum was purified by affinity chromatography. ii. It was demonstrated that the antiserum crossreacts with only those polypeptides which appear to be enzymatically active. In the fraction of broken plastids isolated from leaves of briefly illuminated barley plants the concentration of the enzyme protein was reduced drastically. Our results indicate that this decrease in enzyme protein content is the consequence of an artificial proteolytic breakdown of the membrane-bound enzyme protein. In intact plastids and in the total leaf extract the concentration of the enzyme protein did not change dramatically during the first 4 to 6 h of illumination. However, when the exposure to continuous white light was extended further the concentration of the enzyme protein in intact plastids began to decline rapidly while in total leaf extracts the concentration remained almost constant for the next 10 h of light. These results indicate that part of the enzyme protein may be localized outside of the plastid compartment. PMID- 24232547 TI - Light-induced changes in the distribution of the 36000-Mr polypeptide of NADPH protochlorophyllide oxidoreductase within different cellular compartments of barley (Hordeum vulgare L.) : II. Localization by immunogold labelling in ultrathin sections. AB - The cellular distribution of the 36000-Mr polypeptide of NADPH protochlorophyllide oxidoreductase has been determined in ultrathin sections of barley leaves by the method of immunogold labelling. In leaves of etiolated seedlings a large portion of the immunoreactive protein was localized within the prolamellar body. However, approximately one third of the total immunoreactive protein was present outside the plastid in the area of the plasmalemma. During illumination of etiolated seedlings the two polypeptide populations were differentially affected by light. While the concentration of the plastid localized immunoreactive protein rapidly decreased and was hardly detectable after 16 h of continuous white-light treatment, the concentration of the extraplastidic polypeptide did not decline significantly during this illumination period. A similar distribution pattern of the immunoreactive polypeptide was also found in maize and rye. The chlorophyll-deficient barley mutant xantha-l(81) contained the immunoreactive 36000-Mr polypeptide, even though the prolamellar body was not detectable in etioplasts of this mutant. All of the immunoreactive polypeptide was localized outside the plastid in the area of the plasmalemma. Despite the apparent absence of the enzyme protein from the plastid, dark-grown mutant plants contained the same relative concentration of mRNA activity for the NADPH-protochlorophyllide oxidoreductase, which declined rapidly during illumination, as in wild-type plants. The antigenic properties and the apparent molecular weight of the plastid-localized NADPH-protochlorophyllide oxidoreductase and the 36000-Mr immunoreactive polypeptide outside the plastid were so similar as to indicate that the two proteins may be of common origin. PMID- 24232548 TI - Style proteins of a wild tomato (Lycopersicon peruvianum) associated with expression of self-incompatibility. AB - The identification, isolation and aminoterminal sequencing of two S-genotype associated proteins from style extracts of Lycopersicon peruvianum Mill. is reported. There is a high level of homology between these two sequences and with the amino-terminal sequences of other S-allele-associated glycoproteins isolated from Nicotiana alata Link et Otto. These sequences were obtained by a new high sensitivity method of selected twodimensional gel analysis followed by electroelution and purification of proteins by inverse-gradient high-performance liquid chromatography before sequencing. PMID- 24232549 TI - Isolation of a copper complex and its rate of appearance in roots of Mimulus guttatus. AB - A Cu-complex was isolated from the roots of copper-tolerant Mimulus guttatus. The elution volume of the complex determined by gel permeation chromatography was similar to that of rat-liver cadmium thionein. The complex was heat stable, had a relatively high ratio of absorbance at 254 nm: 280 nm and incorporated (35)S. The complex, purified using a combination of gel permeation chromatography and anion exchange chromatography, contained more glutamine/glutamic acid and glycine residues than mammalian metallothioneins. The amount of the complex in roots increased after 5 h growth in a solution containing 16 MUM Cu. Induction was preceded by an increase in the concentrations in root tissue of unknown compounds containing sulphur which may serve as precursors. The availability of these compounds appeared to regulate the rate of synthesis of this Cu-complex. PMID- 24232550 TI - Phosphoenolpyruvate carboxylase in soybean root nodules: An immunochemical study. AB - The activity of phosphoenolpyruvate carboxylase (E.C. 4.1.1.31) strongly increased during the maturation of soybean (Glycine max L. Weber) root-nodules. By using a specific immune serum it was shown that this increase was the consequence of an elevated population of enzyme molecules whose appearance preceded the emergence of nitrogen fixing capacity. Whether or not the phenomenon could be ascribed to the formation of a specific isoenzyme is not known. The location of the enzyme was also investigated. Immunocyto-fluorescence experiments established that phosphoenolpyruvate carboxylase was present in the cytoplasmic compartment of both infected and uninfected cells of nodules. PMID- 24232551 TI - Nitrate reductase is not accumulated in chloroplast-ribosome-deficient mutants of higher plants. AB - The activities of nitrite reductase (EC 1.7.7.1) are 60-70% of wild-type activity in pigment-deficient leaves of the chloroplast-ribosomedeficient mutants 'albostrians' (Hordeum vulgare) and 'iojap' (Zea mays). The activity and apoprotein of nitrate reductase (EC 1.6.6.1.) are lacking in the barley mutant. Only very low activities of nitrate reductase can be extracted from leaves of the maize mutant. The molybdenum cofactor of nitrate reductase and xanthine dehydrogenase (EC 1.2.3.2) is present in maize and barley mutant plants. However, it is not inducible by nitrate in pigment-deficient leaves of 'albostrians'. From these results we conclude: (i) Nitrite reductase (a chloroplast enzyme) is synthesized in the cytoplasm and does not need the presence of nitrate reductase for the induction and maintenance if its activity. (ii) The loss or low activity of nitrate reductase is a consequence of the inability of the mutants to accumulate the apoprotein of this enzyme. (iii) The chloroplasts influence the accumulation (i.e. most probably the synthesis) of the nonchloroplast enzyme, nitrate reductase. The accumulation of nitrate reductase needs a chloroplast factor which is not provided by mutant plastids blocked at an early stage of their development. PMID- 24232552 TI - Comparison of glutathione S-transferases of Zea mays responsible for herbicide detoxification in plants and suspension-cultured cells. AB - The metabolism of the s-triazine herbicide atrazine has been compared in Zea mays seedlings and cell suspension cultures. The rapid detoxification observed in the shoots of whole plants was not seen in the cultured cells. This difference in metabolism could be accounted for by the varying substrate specificities of the isoenzymes of glutathione S-transferase (EC 2.5.1.18) present in the plant and the cells. A single form of the enzyme isolated from leaf tissue conjugated both atrazine and the chloracetanilide herbicide metolachlor. However, the two isoenzymes present in suspension-cultured cells although active against metolachlor, showed no activity toward atrazine. Following purification, the major form of transferase present in the cells was physically similar to the enzyme isolated from leaf (Mr=55000). Both proteins were dimers of subunit Mr=26300, and with isoelectric points in the range pH 4.3-4.9. The minor form of the enzyme present in culture showed a greater specificity for metolachlor than the major species. In addition the overall activity and ratio of the two isoenzymes varied over the culture growth cycle. These findings illustrate the need for characterizing enzymes involved in herbicide detoxification in plant cell cultures. PMID- 24232553 TI - Breakdown of phosphatidylinositol in soybean callus. AB - We have investigated the breakdown of membrane-bound phosphatidylinositol (PI) in homogenates of soybean (Glycine max) callus. The breakdown of PI was stimulated by the detergent deoxycholate. At pH 7.0 and 1.gl(-1) of deoxycholate the loss of PI was rapid and extensive: more than 80% was broken down within 10 min. The breakdown of PI was also stimulated by millimolar concentrations of Ca(2+). The products of breakdown of added PI (purified from soybean callus) in this system were identified from their chromatographic mobilities as 1,2-diacylglycerol, myo inositol 1-phosphate and myo-inositol 1:2-cyclic monophosphate. PMID- 24232554 TI - Inorganic-carbon uptake by the marine diatom Phaeodactylum tricornutum. AB - Air-grown cells of the marine diatom Phaeodactylum tricornutum showed only 10% of the carbonic-anhydrase activity of air-grown Chlamydomonas reinhardtii. Measurement of carbonic-anhydrase activity using intact cells and cell extracts showed all activity was intracellular in Phaeodactylum. Photosynthetic oxygen evolution at constant inorganic-carbon concentration but varying pH showed that exogenous CO2 was poorly utilized by the cells. Sodium ions increased the affinity of Phaeodactylum for HCO 3 (-) and even at high HCO 3 (-) concentrations sodium ions enhanced HCO 3 (-) utilization. The internal inorganic-carbon pool (HCO 3 (-) +CO2] was measured using a silicone-oil-layer centrifugal filtering technique. The internal [HCO 3 (-) +CO2] concentration never exceeded 15% of the external [HCO 3 (-) +CO2] concentration even at the lowest external concentrations tested. It is concluded that an internal accumulation of inorganic carbon relative to the external medium does not occur in P. tricornutum. PMID- 24232555 TI - Evidence supporting a model of voltage-dependent uptake of auxin into Cucurbita vesicles. AB - The accumulation of [(14)C]indole-3-acetic acid (IAA), of [(3)H]tetra-phenyl phosphonium ion as a membrane potential probe, and of [(14)C]butyric acid as probe for pH gradients was studied with membrane vesicles from etiolated hypocotyls of Cucurbita pepo. Ion gradients (K(+), H(+)) were applied in the presence and absence of specific ionophores e.g. valinomycin or carbonylcyanide m chlorophenylhydrazone. In all cases tested, the accumulation of [(14)C]IAA equals neither potential probe nor pH-probe accumulation, but represents. an intermediate between the two. Auxin molecules seem to be taken up as positively charged ions and a pH gradient is required for accumulation. The uptake mechanism thus appears to be a specific, carrier-mediated cotransport of the anion of IAA and no less than two protons. The initial rates of auxin uptake by the saturable influx carrier, of permeation through the membrane, and of efflux by the phytotropin-affected efflux carrier were analysed. PMID- 24232556 TI - Isolation and characterization of prolyl hydroxylase from Chlamydomonas reinhardii. AB - Prolyl hydroxylase, which is responsible for the hydroxylation of peptidyl proline residues, has been isolated and purified from the green alga Chlamydomonas reinhardii. The enzyme, which appears to be loosely associated with microsomal membranes, was released into solution by sonication in the presence of detergent. Purification was achieved by ion-exchange chromatography followed by affinity chromatography using the immobilized substrate poly-L-proline. Apart from its differing substrate specificity the enzyme appears to possess similar molecular characteristics to prolyl hydroxylase isolated from animal tissues: the active enzyme is a tetramer of about 240-250 kDa and nonidentical monomers of 65 and 60 kDa. The monomers are capsule shaped having a dimension of 12*7 nm. PMID- 24232557 TI - Self-incompatibility in Acacia retinodes: Site of pollen-tube arrest is the nucellus. AB - In self-incompatible Acacia retinodes Schldl. var. uncifolia J.M. Black there is no inhibition of self pollen tubes before entry into the ovule, but the frequency of fertilized embryo sacs observed after self pollination is only 0.09-0.24 of that observed after outcrossing. Fluorescence- and light-microscope studies of sectioned, squashed or cleared whole ovules indicate that most self pollen tubes are arrested within the first or second layer of cells of the nucellus. The probability that nucellar arrest represents a primitive feature of self incompatibility is discussed. PMID- 24232558 TI - Electron transport across the plasmalemma of Lemna gibba G1. AB - Lemna gibba L., grown in the presence or absence of Fe, reduced extracellular ferricyanide with a V max of 3.09 MUmol . g(-1) fresh weight . h(-1) and a K m of 115 MUM. However, Fe(3+)-ethylenediaminetetraacetic acid (EDTA) was reduced only after Fe-starvation. External electron acceptors such as ferricyanide, Fe(3+) EDTA, 2,6-dichlorophenol indophenol or methylene blue induced a membrane depolarization of up to 100 mV, but electron donors such as ferrocyanide or NADH had no effect. Light or glucose enhanced ferricyanide reduction while the concomitant membrane depolarization was much smaller. Under anaerobic conditions, ferricyanide had no effect on electrical membrane potential difference (Em). Ferricyanide reduction induced H(+) and K(+) release in a ratio of 1.16 H(+)+1 K(+)/2 e(-) (in +Fe plants) and 1.28 H(+)+0.8 K(+)/2 e(-) (in -Fe plants). Anion uptake was inhibited by ferricyanide reduction. It is concluded that the steady state transfer of electrons and protons proceeds by separate mechanisms, by a redox system and by a H(+)-ATPase. PMID- 24232559 TI - Regulatory factors involved in gene expression (subunits of ribulose-1,5 bisphosphate carboxylase) in mustard (Sinapis alba L.) cotyledons. AB - Phytochrome-controlled appearance of ribulose-1,5-bisphosphate carboxylase (RuBP Case) and its subunits (large subunit LSU, small subunit SSU) was studied in the cotyledons of the mustard (Sinapis alba L.) seedling. The main results were as follows: (i) Control of RuBPCase appearance by phytochrome is a modulation of a process which is turned on by an endogenous factor between 30 and 33 h after sowing (25 degrees C). Only 12 h later the process begins to respond to phytochrome. (ii) The rise in the level of RuBP-Case is the consequence of a strictly coordinated synthesis de novo of the subunits. (iii) While the levels of translatable mRNA for SSU are compatible with the rate of SSU synthesis the relatively high LSU mRNA levels are not reflected in the rates of in-vivo LSU or RuBPCase syntheses. (iv) Gene expression is also abolished in the case of nuclear encoded SSU if intraplastidic translation and concomitant plastidogenesis is inhibited by chloramphenicol, pointing to a "plastidic factor" as an indispensable prerequisite for expression of the SSU gene(s). (v) Regarding the control mechanism for SSU gene expression, three factors seem to be involved: an endogenous factor which turns on gene expression, phytochrome which modulates gene expression, and the plastidic factor which is an indispensable prerequisite for the appearance of translatable SSU mRNA. PMID- 24232560 TI - Reduced and oxidised glutathione and glutathione-reductase activity in tissues of Pisum sativum. AB - In three-week-old pea plants (Pisum sativum L., cv. Little Marvel) grown in the light, total glutathione levels were highest in apex and expanding leaves (1.5 MUmol.(g FW)(-1)), and lower (0.4-0.6 MUmol.(g FW)(-1)) in older leaves and roots. In the light period, levels in expanded leaves increased by about 40%, compared with dark values, with lesser increases in roots and apex. In illuminated plants the proportion in the reduced form was 86-88% in leaves and 80% in roots, and these values fell during the dark period (to 82% and 69%, respectively). Reduced glutathione makes up 65-70% of the low-molecular-weight thiol in leaves, but over 95% in roots. Chloroplasts contained about 10% of the leaf glutathione, at a concentration of 1-2 mM; total glutathione in the chloroplasts, and the proportion of oxidised form (GSSG) increased in light, while NADP(+)/NADPH ratios decreased, indicating both synthesis and active oxidation of glutathione in light. Chloroplasts contained 52% (young leaf) to 75% (mature leaf) of the GSSG-reductase (EC 1.6.4.2) activity in the leaves. In roots, over 30% of the GSSG reductase was in the plastid fraction. Very little GSSG-reductase activity was associated with mitochondria in leaf or root. PMID- 24232561 TI - De-novo synthesis and release of peroxidases in cell suspension cultures of Nicotiana tabacum L. AB - De-novo synthesis of acid and basic peroxidases has been studied in cell suspension cultures of tobacco by incorporation of (3)H- and (14)C-amino acids. Incorporation rates were found to be high for acid peroxidases and low for basic peroxidases. Synthesis of all peroxidases was inhibited by cycloheximide and actinomycin D. Subculturing of the cells increased the rates of radioactive amino acid incorporation into all peroxidases within the first 24 h. This rise in peroxidase synthesis was correlated with the age of the transferred cells. The older the cells were the more pronounced was the effect. During the culture cycle the high rates of peroxidase synthesis at the second day dropped back to initial values. Peroxidase synthesis was thus inversely related to peroxidase accumulation which was very low at the beginning and increased continuously. By pulse-chase experiments it has been shown that newly synthesized acid peroxidases accumulated in the medium. This process was inhibited by monensin. Only the acid peroxidases were secreted into the cell wall and from there released. The basic peroxidases were not detectable in the medium. PMID- 24232562 TI - Is protein degradation correlated with either the charge or size of Lemna proteins? AB - Evidence is presented that the organelles of Lemna minor do not degrade as functional units. The proteins of Lemna show wide differences in their rates of degradation and ribulose bisphosphate carboxylase (EC 4.1.1.39) has a particularly slow rate of degradation. Contrary to some earlier evidence, we found no correlation between the rate of soluble-protein degradation and either charge or size of proteins. We could find no correlation between protein degradation and subunit size in any of the organelles of Lemna. PMID- 24232563 TI - Promotion of flower formation by atrazine and diuron in seedlings of Asparagus. AB - Flower formation in 25-d-old seedling of Asparagus officinalis L was increased by soaking the seeds for 12 d in solutions of atrazine (2-chloro-4-ethylamino-6 isopropylamino-1,3,5-triazine) or diuron (3-(3,4-dichlorophenyl)-1,1 dimethylurea), two herbicides known to affect electron flow of photosystem II, from approx. 4% in controls to 37% in treatments with 400 MUM of atrazine or about 100 MUM diuron. Both herbicides inhibited plant growth, but treatment of seeds with other growth inhibitors (absicic acid, (2 chloroethyl)trimethylammonium chloride, polyethylene glycol) did not affect flower formation although inhibiting seed germination and plant growth. The increase of flower formation by the two herbicides permits identification of the sex of Asparagus plants at an early developmental stage. PMID- 24232567 TI - Playing fast and loose with mutation. PMID- 24232568 TI - Development of vaccines for Candida albicans: fighting a skilled transformer. AB - Two univalent subunit vaccines that are based on major virulence traits of Candida albicans have completed Phase I clinical trials in recent years. Although it is hoped that at least one will become the first antifungal vaccine approved for human use, there are some major obstacles to achieving this. The difficulties mostly arise from the remarkable ability of C. albicans to deceive the host immune system. In this Opinion article, I argue that the development of a multivalent vaccine that induces an immune response against multiple, unrelated virulence traits of this human commensal fungus and opportunistic pathogen may be a better approach. PMID- 24232569 TI - Marked ethnic, nativity, and socioeconomic disparities in disability and health insurance among US children and adults: the 2008-2010 American community survey. AB - We used the 2008-2010 American Community Survey Micro-data Sample (N = 9,093,077) to estimate disability and health insurance rates for children and adults in detailed racial/ethnic, immigrant, and socioeconomic groups in the USA. Prevalence and adjusted odds derived from logistic regression were used to examine social inequalities. Disability rates varied from 1.4% for Japanese children to 6.8% for Puerto Rican children. Prevalence of disability in adults ranged from 5.6% for Asian Indians to 22.0% among American Indians/Alaska Natives. More than 17% of Korean, Mexican, and American Indian children lacked health insurance, compared with 4.1% of Japanese and 5.9% of white children. Among adults, Mexicans (43.6%), Central/South Americans (41.4%), American Indians/Alaska Natives (32.7%), and Pakistanis (29.3%) had the highest health uninsurance rates. Ethnic nativity disparities were considerable, with 58.3% of all Mexican immigrants and 34.0% of Mexican immigrants with disabilities being uninsured. Socioeconomic gradients were marked, with poor children and adults having 3-6 times higher odds of disability and uninsurance than their affluent counterparts. Socioeconomic differences accounted for 24.4% and 60.2% of racial/ethnic variations in child health insurance and disability and 75.1% and 89.7% of ethnic inequality in adult health insurance and disability, respectively. Health policy programs urgently need to tackle these profound social disparities in disability and healthcare access. PMID- 24232570 TI - AMACO is a component of the basement membrane-associated Fraser complex. AB - Fraser syndrome (FS) is a phenotypically variable, autosomal recessive disorder characterized by cryptophthalmus, cutaneous syndactyly, and other malformations resulting from mutations in FRAS1, FREM2, and GRIP1. Transient embryonic epidermal blistering causes the characteristic defects of the disorder. Fras1, Frem1, and Frem2 form the extracellular Fraser complex, which is believed to stabilize the basement membrane. However, several cases of FS could not be attributed to mutations in FRAS1, FREM2, or GRIP1, and FS displays high clinical variability, suggesting that there is an additional genetic, possibly modifying contribution to this disorder. An extracellular matrix protein containing VWA like domains related to those in matrilins and collagens (AMACO), encoded by the VWA2 gene, has a very similar tissue distribution to the Fraser complex proteins in both mouse and zebrafish. Here, we show that AMACO deposition is lost in Fras1 deficient zebrafish and mice and that Fras1 and AMACO interact directly via their chondroitin sulfate proteoglycan (CSPG) and P2 domains. Knockdown of vwa2, which alone causes no phenotype, enhances the phenotype of hypomorphic Fras1 mutant zebrafish. Together, our data suggest that AMACO represents a member of the Fraser complex. PMID- 24232571 TI - Role of intracellular stochasticity in biofilm growth. Insights from population balance modeling. AB - There is increasing recognition that stochasticity involved in gene regulatory processes may help cells enhance the signal or synchronize expression for a group of genes. Thus the validity of the traditional deterministic approach to modeling the foregoing processes cannot be without exception. In this study, we identify a frequently encountered situation, i.e., the biofilm, which has in the past been persistently investigated with intracellular deterministic models in the literature. We show in this paper circumstances in which use of the intracellular deterministic model appears distinctly inappropriate. In Enterococcus faecalis, the horizontal gene transfer of plasmid spreads drug resistance. The induction of conjugation in planktonic and biofilm circumstances is examined here with stochastic as well as deterministic models. The stochastic model is formulated with the Chemical Master Equation (CME) for planktonic cells and Reaction Diffusion Master Equation (RDME) for biofilm. The results show that although the deterministic model works well for the perfectly-mixed planktonic circumstance, it fails to predict the averaged behavior in the biofilm, a behavior that has come to be known as stochastic focusing. A notable finding from this work is that the interception of antagonistic feedback loops to signaling, accentuates stochastic focusing. Moreover, interestingly, increasing particle number of a control variable could lead to an even larger deviation. Intracellular stochasticity plays an important role in biofilm and we surmise by implications from the model, that cell populations may use it to minimize the influence from environmental fluctuation. PMID- 24232572 TI - Regression of cerebellar tonsillar descent and hydrocephalus after endoscopic third ventriculostomy in a patient with a quadrigeminal arachnoid cyst. AB - BACKGROUND: Posterior fossa arachnoid cysts, including quadrigeminal cistern arachnoid cysts, can occasionally cause compression of the quadrigeminal plate, leading to Sylvian aqueduct stenosis and induction of cerebellar tonsillar descent into the foramen magnum. This, in turn, can result in obstructive hydrocephalus. In such cases, the characteristic of hydrocephalus is generally considered to be hypertensive. CASE DESCRIPTION: We present the case of a 28-year old female complaining of chronic and progressively worsening headaches following the delivery of her first child. Magnetic resonance imaging revealed marked tri ventriculomegaly, the arachnoid cyst located in the quadrigeminal cistern, and cerebellar tonsillar descent. Ophthalmoscopy revealed bilateral papilledema indicating a long-standing elevation of intracranial pressure. Endoscopic third ventriculostomy (ETV) was performed successfully and resulted in complete recovery from her headaches and papilledema. Postoperative MRI revealed resolution of ventriculomegaly and cerebellar tonsillar descent, suggesting that the fourth ventricle outlet obstruction was associated with the development of the hydrocephalus in this patient. CONCLUSION: Our case is the first report that a quadrigeminal arachnoid cyst associated with both cerebellar tonsillar descent and hydrocephalus was well treated with ETV. It was indicated that the patient's hydrocephalus and cerebellar tonsillar descent were secondary and synergistic events, caused by the arachnoid cyst located in the quadrigeminal cistern. PMID- 24232573 TI - Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus. AB - Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co culture experiments between the white variants and a selected number of Gram positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP synthase], hfq). In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant of S. aureus which is activated by a co infecting P. aeruginosa via inter-species communication. Another S. aureus virulence factor, catalase is also induced by this co-infecting bacterium. The resulting phenotypic changes are directly correlated with resistance of the white variant to stressful conditions. PMID- 24232574 TI - The brachyury Gly177Asp SNP is not associated with a risk of skull base chordoma in the Chinese population. AB - A recent chordoma cancer genotyping study reveals that the rs2305089, a single nucleotide polymorphism (SNP) located in brachyury gene and a key gene in the development of notochord, is significantly associated with chordoma risk. The brachyury gene is believed to be one of the key genes involved in the pathogenesis of chordoma, a rare primary bone tumor originating along the spinal column or at the base of the skull. The association between the brachyury Gly177Asp single nucleotide polymorphism (SNP) and the risk of skull base chordoma in Chinese populations is currently unknown. We investigated the genotype distribution of this SNP in 65 skull-base chordoma cases and 120 healthy subjects. Comparisons of the genotype distributions and allele frequencies did not reveal any significant difference between the groups. Our data suggest that the brachyury Gly177Asp SNP is not involved in the risks of skull-base chordoma, at least in the Chinese population. PMID- 24232576 TI - Synthesis and characterization of ferroelectric liquid crystalline organosiloxanes containing 4-(4-undecanyloxy bi-phenyl-1-carboxyloxy)phenyl (2S,3S)-2-chloro-3-methylvalerate and 4-(4-undecanyloxybenzoyloxy)biphenyl (2S,3S)-2-chloro-3-methylvalerate. AB - A series of new organosiloxane ferroelectric liquid crystalline (FLC) materials have been synthesized, and their mesomorphic and physical properties have been characterized. Four new disiloxanes and trisiloxanes, containing biphenyl 4 hydroxybenzoate and phenyl 4-hydroxybiphenylcarboxylate as mesogenic units and eleven methylene unit as spacers and (2S,3S)-2-chloro-3-methylvalerate unit as chiral end groups. The molecule, using three phenyl ring as a mesogenic unit, formulates much wider liquid crystalline phase temperature ranges than that of a two phenyl ring unit. The phenyl arrangement differences of mesogenic unit result in the greater differences of the liquid crystal phase formation. The siloxane molecule induction is helpful to the more regular smectic phase formation and smectic phase stabilization, such as chiral SC (SC*) and SB phases. The siloxane molecule is helpful to reduce the phase transition temperature and broaden the liquid crystal temperature range of the SC* phase and, simultaneously, it will not induce chain crystallization phenomenon and dilute the Ps value. The synthesis and characterization of the new FLCs materials, which exhibit a room temperature SC* phase and higher spontaneous polarization are presented. PMID- 24232575 TI - Magnetic nanoparticles: surface effects and properties related to biomedicine applications. AB - Due to finite size effects, such as the high surface-to-volume ratio and different crystal structures, magnetic nanoparticles are found to exhibit interesting and considerably different magnetic properties than those found in their corresponding bulk materials. These nanoparticles can be synthesized in several ways (e.g., chemical and physical) with controllable sizes enabling their comparison to biological organisms from cells (10-100 MUm), viruses, genes, down to proteins (3-50 nm). The optimization of the nanoparticles' size, size distribution, agglomeration, coating, and shapes along with their unique magnetic properties prompted the application of nanoparticles of this type in diverse fields. Biomedicine is one of these fields where intensive research is currently being conducted. In this review, we will discuss the magnetic properties of nanoparticles which are directly related to their applications in biomedicine. We will focus mainly on surface effects and ferrite nanoparticles, and on one diagnostic application of magnetic nanoparticles as magnetic resonance imaging contrast agents. PMID- 24232577 TI - Enhanced solar cell conversion efficiency using birefringent liquid crystal polymer homeotropic films from reactive mesogens. AB - Novel birefringent liquid crystal polymer homeotropic films have been coated on semiconductor solar cells to improve the effective incident sunlight angles. The liquid crystal polymer precursor, based on reactive mesogens, is fluidic and flows like liquid. It would distribute uniformly on the solar cell sample surface by any traditional coating technique. The birefringence for light, due to the liquid crystal retardation properties, manipulated the optical length and the deflection of incident light, thus allowed an increase in the energy conversion efficiency. The expensive sunlight tracking systems could be avoided. The processing parameters can be tuned such as different mesogen concentrations and plate speeds of spin-coating. The results showed that the solar cell conversion efficiency was improved from 14.56% to 14.85% at an incident sunlight angle of 15 degrees . It was further improved from 13.40% to 13.81% when the angle was 30 degrees . The interesting angular dependency on solar cell efficiency enhancement has been evaluated. PMID- 24232578 TI - Quinolinic acid: neurotoxin or oxidative stress modulator? AB - Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) is a well-known neurotoxin. Consequently, QUIN could produce reactive oxygen species (ROS). ROS are generated in reactions catalyzed by transition metals, especially iron (Fe). QUIN can form coordination complexes with iron. A combination of differential pulse voltammetry, deoxyribose degradation and Fe(II) autoxidation assays was used for explorating ROS formation in redox reactions that are catalyzed by iron in QUIN Fe complexes. Differential pulse voltammetry showed an anodic shift of the iron redox potential if iron was liganded by QUIN. In the H2O2/FeCl3/ascorbic acid variant of the deoxyribose degradation assay, the dose-response curve was U shaped. In the FeCl3/ascorbic acid variant, QUIN unambiguously showed antioxidant effects. In the Fe(II) autoxidation assay, QUIN decreased the rate of ROS production caused by Fe(II) oxidation. Our study confirms that QUIN toxicity may be caused by ROS generation via the Fenton reaction. This, however, applies only for unnaturally high concentrations that were used in attempts to provide support for the neurotoxic effect. In lower concentrations, we show that by liganding iron, QUIN affects the Fe(II)/Fe(III) ratios that are beneficial to homeostasis. Our results support the notion that redox chemistry can contribute to explaining the hormetic dose-response effects. PMID- 24232579 TI - Requests of electrodiagnostic testing: consistency and agreement of referral diagnosis. What is changed in a primary outpatient EMG lab 16 years later? AB - The aims are to evaluate electrodiagnostic testing (EDX) requests and verify if presence, consistency and agreement of referral diagnosis could be predicted by patient demographic findings and referring physician typology, and if there were differences in respect to our previous study performed 16 years ago. The study concerns EDX requests referred to two electromyography labs during the year 2011. Differences between findings of general practitioners (GPs) versus specialists' requests and between this study with the previous were assessed. Multivariate logistic regression was performed to calculate odds ratio to assess the strength of association between presence, consistency and agreement of referral diagnosis with patient demographic findings and referring physician typology. We evaluated EDX requests of 1,586 patients (mean age 56 +/- 16.7 years, 58.8 % women), 1,050 (66.2 %) were referred by GPs and 536 (33.8 %) by specialists. The suspected diagnosis was reported in 1,033 (65.1 %) requests, the overall consistency was 79.9 % and agreement was 71.9 %. Presence, consistency and agreement of referral diagnosis were predicted by physician's typology (specialist). Only if the suspected diagnosis was carpal tunnel syndrome, consistency and agreement were high regardless of doctor's typology. The physicians, especially GPs, who reported the referral diagnosis decreased during the past 16 years. A diagnostic test, including EDX, should be considered mainly if it fits into the best diagnostic strategy. The neurophysiologist should decide if EDX is useful, make the best decision on further management, and not submit patients to unnecessary and uncomfortable procedures. This choice of behaviour could be questionable and may lead to ethical and deontological problems. PMID- 24232580 TI - Retinal implants: analysis of the news media perspective. PMID- 24232581 TI - Metronomic capecitabine in advanced hepatocellular carcinoma patients: a phase II study. AB - Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. METHODS: This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. RESULTS: A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). CONCLUSION: Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib. PMID- 24232582 TI - Preferences for gender-targeted health information: a study of male veterans who have experienced military sexual trauma. AB - No prior research has examined men's opinions or preferences regarding receiving health education materials related to sexual violence. The objective of the current study was to investigate whether male veteran patients who have experienced military sexual trauma (MST) prefer gender-targeted versus gender neutral printed health information and whether receipt of this information increased utilization of outpatient mental health services in the following 6 month period. In-person 45-minute interviews were conducted with 20 male veterans receiving health care services at a large Veterans Health Administration facility to evaluate opinions on a gender-targeted and a gender-neutral brochure about MST. An additional 153 veterans received psychoeducational materials through the mail and participated in the completion of a survey as part of a psychoeducational intervention. Our results demonstrate that male veterans prefer gender-targeted information about sexual trauma compared to gender-neutral information. Whereas veterans in the study had clear preferences for gender targeted materials, receipt of information about MST (whether gender-targeted or gender-neutral) did not increase utilization of mental health care in the 6 months following receipt of these materials. These results demonstrated that materials about sexual trauma are acceptable to men and should be gender targeted. Further research is needed to examine strategies to increase access to mental health care among male Veterans who have experienced MST. PMID- 24232583 TI - Sex, HIV, and the Internet: Exploring Variations in the Online Profiles of MSM in the United States. AB - With the increasing pervasiveness of social media, the Internet has become an important venue for dating and sex. Not only does the Internet introduce a unique array of opportunities and risks for men who have sex with men (MSM), it also presents a valuable means through which to study sexual behavior. In this study, data on what men report in their online profiles were collected from two dating/hookup websites to explore possible geographical differences in men's sexual preferences and expectations (N = 5,588). Across the 15 selected cities, significant differences emerged in reported HIV status and stated preference for safer sex (condom use). These patterns suggest important contextual and demographic variations and point to a need for targeted, population-specific interventions and further research to identify the underlying social and psychological constructs. With a better understanding of the local factors driving risky sexual behavior, health communication messages and tailored online interventions could be developed to address the needs and concerns of specific groups. PMID- 24232584 TI - Plant regeneration from cell suspension cultures ofArabidopsis thaliana heynh. AB - A technique is described for the establishment, maintenance, and regeneration of plants from cell suspension cultures ofArabidopsis thaliana (L) Heynh. Friable, rapidly growing cell suspension cultures were initiated from leaf or hypocotyl callus cultures and these have been maintained in liquid culture for 24 months. The cells grown in liquid culture were used to study the effects of growth regulators, medium salts composition, culture temperature, sucrose concentration and medium solidifying agents on morphogenesis. The most important parameters for plant regeneration were culture temperatures lower than 25 degrees C, the medium solidification agent gelrite at 0.2% (w/v) and zeatin or thidiazuron as the choice of cytokinin. These cell suspensions continue to regenerate fertile plants with a total of over 200 plants having been rooted to date and they also serve as convenient sources of cells for protoplast isolation, biochemical, and molecular assays. PMID- 24232585 TI - Messenger RNA induction in cellular salt tolerance of Alfalfa (Medicago sativa). AB - A salt tolerant alfalfaMedicago sativa L. cell line (HG2-N1) has been selected for growth in 171 mM NaCl. The salt tolerance characteristic is stable and is retained after growth in absence of salt selection for two months.In vitro translation was used to compare mRNA composition from the salt tolerant HG2-N1 and parent salt sensitive HG2 cell lines grown in the presence and absence of 171 mM NaCl. The results suggest that the mRNA composition differs between HG2-N1 and HG2 in a number of RNA species. The salt tolerant HG2-N1 shows both increases and decreases in specific polypeptides as compared to HG2. Many of the enhanced polypeptide bands from mRNA in the salt tolerant HG2-N1 variant appear to be constitutively expressed, since they can be detected from HG2-N1 cells grown in presence and absence of NaCl, but the expression of a few bands may depend on the presence of added NaCl. Most enhanced polypeptides, which are detected from mRNA in the salt tolerant variant HG2-N1 (grown on NaCl) are different from polypeptide bands enhanced in the salt sensitive HG2 line as a result of 24 hour salt stress. Similar results were obtained from two dimensional analysis ofin vivo labeled polypeptides. At least one isolated cDNA clone shows selective expression of mRNA in salt tolerant cells grown in NaCl. These results indicate that adaptive mechanisms for salt tolerance may differ in some aspects from acute stress mechanisms. PMID- 24232586 TI - Hairy roots - a short cut to transgenic root nodules. AB - To facilitate molecular studies of symbiotic nitrogen fixation a procedure for rapid production of transgenic root nodules was established on the legumeLotus corniculatus (Bird'sfoot trefoil). Regeneration of transgenic plants is not required as transgenic nodules are formed onAgrobacterium rhizogenes incited roots inoculated withRhizobium. Easy identification of transformed roots is possible using a set ofA. rhizogenes acceptor strains carrying assayable marker genes such as chloramphenicol acetyltransferase (CAT), beta-glucuronidase (GUS), or luciferase (LUC) under control of the cauliflower mosaic virus (CaMV) 35S promoter. Counterselection ofA. rhizogenes after infection of plants was improved using an auxotrophy marker. PMID- 24232587 TI - Transformation of white spruce and other conifer species byAgrobacterium tumefaciens. AB - Studies of the ability ofAgrobacterium to transform white spruce (Picea glauca), Engelmann spruce (P. engelmanni), Sitka spruce (P. sitchensis) and Douglas-fir (Pseudotsuga menziesii) showed frequencies of gall formation from 0-80% depending upon the strain ofAgrobacterium, and the conifer species. Thirty sixA. tumefaciens strains and oneA. rhizogenes strain were tested on 6 month old white spruce seedlings. NineA. tumefaciens strains induced gall formation on more than 50% of the inoculated trees and at greater than 10% of the inoculated sites. One strain, B2/74 gave rise to galls at 28% of the inoculated sites on white spruce and induced the highest overall frequency of gall formation on all the conifer species tested. Relative frequency of gall formation was consistent among species, although the overall frequency was much higher on Douglas-fir. Of the well characterized strains for which disarmed derivatives are available only A281 (carrying the supervirulent tumor inducing plasmid, pTiBo542) gave efficient transformation. Stable integration of T-DNA encoded genes has been confirmed by the expression of opine synthesis and hormone autonomous growth. The transfer and long-term stable expression of kanamycin resistance and firefly luciferase activity using binary vector systems was also achieved. PMID- 24232588 TI - Plant regeneration from stem cortex protoplasts of a tomato hybrid. AB - Longitudinal sections containing cortical cells taken from stem internodes of a hybrid betweenLycopersicon esculentum andSolanum lycopersicoides were used as tissue sources for enzymatic protoplast isolation. Greenhouse and growth room grown plants 4-8 weeks after rooting could be used as sources of donor tissue. Protoplasts from these tissues divided within 2-4 days of culture and numerous microcalli formed within 30 days. The shoot regeneration frequency of protoplast derived calli was in the order of 60%. More than 100 regenerated plants which appear phenotypically normal have been established in soil. PMID- 24232589 TI - Polysaccharides in the culture medium of cotton (Gossypium hirsutum L.) ovules cultured in vitro. AB - Polysaccharides secreted into the culture medium (PCM) from cotton (Gossypium hirsutum L.) ovules, culturedin vitro, have been examined. The amount of the polysaccharides increases with the duration of the culture, but except for the galactose content, does not vary markedly with the culture age. Analysis shows that the polysaccharide mixture contains mainly pectins, but there is also a significant amount of xyloglucan. The source of the polysaccharides is most likely the callus tissue which develops on the ovules. PMID- 24232590 TI - Production of somatic hybrid tissues following chemical and electrical fusion of protoplasts from albino cell suspensions ofMedicago sativa andM. borealis. AB - Protoplasts isolated from cell suspensions of albinoMedicago borealis andM. sativa were fused chemically, using two methods, and electrically. Although a small scale method of chemical fusion gave the highest fusion frequency, electrofusion was the superior technique on the basis of throughput of green somatic hybrid cell colonies. Chlorophyll-containing tissues were confirmed as being somatic hybrid by isoenzyme and cytological analyses. This is the first report of the application of albino complementation to produce somatic hybrid cells in forage legumes. PMID- 24232591 TI - Expression of a chimaeric kanamycin resistance gene introduced into the wild soybeanGlycine canescens using a cointegrate Ri plasmid vector. AB - Seedling hypocotyl explants ofGlycine canescens were inoculated withAgrobacterium rhizogenes carrying a chimaeric NPTII gene cointegrated into the TL-DNA of pRiA4. Transformed roots produced shoots on B5 based medium with 10.0 mgl(-1) BAP, 0.05 mgl(-1) IBA and 50 MUgml(-1) kanamycin. Cultured roots and regenerated plants expressed NPTII enzyme activity which was correlated with the presence of Ri TL DNA and the structural sequence of the NPTII gene. PMID- 24232592 TI - Heat shock protein expression in thermotolerant and thermosensitive lines of cotton. AB - The expression of heat shock proteins (HSPs) was compared between genetically characterized heat tolerant and heat sensitive lines of cotton (Gossypium hirsutum andG. barbadense) using electrophoretic analysis ofin vivo labelled proteins. No differences were observed between the two lines with regard to: the temperature at which HSP synthesis was induced (37 degrees C); the temperature at which HSP synthesis was maximal (45 degrees C); the rates of recovery from HSP synthesis; the duration of HSP synthesis; or the major size classes of HSPs expressed in these two lines. Several HSPs were identified on 2D gels which were expressed uniquely in either the tolerant or sensitive cotton line. However, the HSP pattern displayed in a heat tolerant BC-3 individual was that of the heat sensitive parent. PMID- 24232593 TI - Plantlet production through high frequency somatic embryogenesis in long term cultures ofEucalyptus citriodora. AB - A highly embryogenic culture ofEucalyptus citriodora was obtained by repetitive embryogenesis from somatic embryos cultured in the dark on a medium containing 500 mg/l each of glutamine and casein hydrolysate, 30 g/l of sucrose and 5 mg/l of 1-napthaleneacetic acid. Cultures retained morphogenetic ability for upto 36 months when maintained at 27 degrees C by subculture at intervals of 4-5 weeks. The subculture period could be extended beyond 9 months if cultures were incubated at 10 degrees C. On a hormone free medium incubated in light 50% of the embryos germinated to plantlets of which 70% survived when transferred to a sand and soil mixture. PMID- 24232594 TI - In vitro propagation and low temperature storage ofSaussurea lappa C.B. Clarke - An endangered, medicinal plant. AB - A procedure forin vitro multiplication ofSaussurea lappa (Asteraceae) is described. On Murashige and Skoog's medium (MS) containing benzylaminopurine and gibberellin 3.5-fold shoot multiplication occurred every three weeks. Shoots rooted on MS containing 0.5 MUM naphthaleneacetic acid with 90% efficiency. The shoot cultures stored at 5 degrees C in the dark for 12 months without an intervening subculture survived with 100% viability. The shoots cold stored for 6 months or more showed higher rates of multiplication under culture room conditions than the untreated shoots. PMID- 24232595 TI - Sterol and sesquiterpenoid biosynthesis during a growth cycle of tobacco cell suspension cultures. AB - The accumulation and biosynthesis of sterols and fungal elicitor-inducible sesquiterpenoids by tobacco (Nicotiana tabacum) cell suspension cultures were examined as a function of a 10 day culture cycle. Sterols accumulated concomitantly with fresh weight gain. The rate of sterol biosynthesis, measured as the incorporation rate of [(14)C]acetate and [(3)H]mevalonate, was maximal when the cultures entered into their rapid phase of growth. Changes in squalene synthetase enzyme activity correlated more closely with thein vivo synthesis rate and accumulation of sterols than 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) enzyme activity. Cell cultures entering into the rapid phase of growth also responded maximally to fungal elicitor as measured by the production of capsidiol, an extracellular sesquiterpenoid. However, the rate of sesquiterpenoid biosynthesis, measured as the incorporation rate of [(14)C]acetate and [(3)H]mevalonate, could not be correlated with elicitor-inducible HMGR or sesquiterpene cyclase enzyme activities, nor elicitor-suppressible squalene synthetase enzyme activity. PMID- 24232596 TI - Vertebral column resection for complex congenital kyphoscoliosis and type I split spinal cord malformation. AB - INTRODUCTION: Congenital progressive kyphoscoliosis associated with split spinal cord malformation (SSCM) is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 23-year-old woman who was found kyphoscoliosis when she was 10 years old and developed rapidly. Thereafter, no management was proposed before her consultation at our center. On examination, numbness was found in the right low limbs, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view and curvature of the thoracolumbar spine was left sided, the left rib hump was severe and there was little muscle tissue felt under the right side paravertebral area, the pelvis was oblique with the right side higher than the left side, the right arcus costarum was 5 cm below the right iliac crest. One-stage corrective surgery was determined, at first, halo wheelchair traction gradually with increased traction weights out of hospital for a month; then, after a reasonable correction achieved without any neurological deficits. The one-stage operation was taken through single posterior segmental pedicle screw instrumented fusion with VCR between T12 and L1. Post-operative recovery was uneventful and there were no complications, she was discharged 10 days post operation. At 2 years follow-up, the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based on the Grand Round case and relevant literature, we discuss the different options for the treatment of congenital kyphoscoliosis associated with type I SSCM. In the patient whose kyphoscoliosis is severe and rigid, we recommend an initial release followed by halo-wheelchair traction gradually to correct the deformity, once optimal correction acquires during the traction, the posterior instrumented fusion with VCR upper the bony spur could be done safely without the resection of bony spur. PMID- 24232598 TI - Comment on Zhu et al. entitled ''Anterior approach versus posterior approach for the treatment of multilevel cervical spondylotic myelopathy: a systemic review and meta-analysis''. PMID- 24232599 TI - C4 anterior cervical corpectomy with fusion for cervical spondylotic myelopathy. PMID- 24232597 TI - Effect of norepinephrine on spinal cord blood flow and parenchymal hemorrhage size in acute-phase experimental spinal cord injury. AB - PURPOSE: In the acute phase of spinal cord injury (SCI), ischemia and parenchymal hemorrhage are believed to worsen the primary lesions induced by mechanical trauma. To minimize ischemia, keeping the mean arterial blood pressure above 85 mmHg for at least 1 week is recommended, and norepinephrine is frequently administered to achieve this goal. However, no experimental study has assessed the effect of norepinephrine on spinal cord blood flow (SCBF) and parenchymal hemorrhage size. We have assessed the effect of norepinephrine on SCBF and parenchymal hemorrhage size within the first hour after experimental SCI. METHODS: A total of 38 animals were included in four groups according to whether SCI was induced and norepinephrine injected. SCI was induced at level Th10 by dropping a 10-g weight from a height of 10 cm. Each experiment lasted 60 min. Norepinephrine was started 15 min after the trauma. SCBF was measured in the ischemic penumbra zone surrounding the trauma epicenter using contrast-enhanced ultrasonography. Hemorrhage size was measured repeatedly on parasagittal B-mode ultrasonography slices. RESULTS: SCI was associated with significant decreases in SCBF (P = 0.0002). Norepinephrine infusion did not significantly modify SCBF. Parenchymal hemorrhage size was significantly greater in the animals given norepinephrine (P = 0.0002). CONCLUSION: In the rat, after a severe SCI at the Th10 level, injection of norepinephrine 15 min after SCI does not modify SCBF and increases the size of the parenchymal hemorrhage. PMID- 24232600 TI - ZnO(N)-Spiro-MeOTAD hybrid photodiode: an efficient self-powered fast-response UV (visible) photosensor. AB - Organic-inorganic hybrid photo-detectors with a self-sufficient mode of operation represent a research area of great current interest. In most efficient photodetectors and optoelectronic devices compound semiconductors containing toxic elements such as Cd, As, Te, S, Se etc. are used and these are also expensive. Hence there is also a rapidly growing interest in replacing these with environmentally friendly and earth-abundant materials. Herein, we report a facile solution-processed fabrication of a self-powered organic-inorganic hybrid photodetector using n-type oriented ZnO nanorods and p-type Spiro-MeOTAD semiconductor. ZnO is eco-friendly and earth-abundant, and Spiro-MeOTAD is non hazardous. We show that the latter has far less toxicity than the toxic elements stated above. This visible blind UV photodetector shows high sensitivity (10(2)) and a UV/visible rejection ratio of 300. It also exhibits fast response times of tau(rise) ~ 200 MUs and tau(fall) ~ 950 MUs. Importantly, with a small modification of nitrogen incorporation in ZnO one can also realize a highly sensitive self-powered visible light photodetector with at least 1000% (or higher) improvements in quality factors (photocurrent/sensitivity/response time) as compared to previously reported organic-inorganic hybrid photo-detectors based on metal-chalcogenides (CdS-PANI or CuInSe2-P3HT). Interestingly, the broadband sensitivity of such N:ZnO-Spiro-MeOTAD photodiode enables sensing of low intensity (~28 MUW cm(-2)) ambient white light with a high photocurrent density of 120 nA cm(-2) making it an efficient ambient white light detector. PMID- 24232601 TI - Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population. AB - Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95% confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR=1.206, 95 % CI=0.972-1.495, p =0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor. PMID- 24232602 TI - A single nucleotide polymorphism of porcine MX2 gene provides antiviral activity against vesicular stomatitis virus. AB - The objective was to determine if single nucleotide polymorphisms (SNPs) in porcine MX2 gene affect its antiviral potential. MX proteins are known to suppress the multiplication of several viruses, including influenza virus and vesicular stomatitis virus (VSV). In domestic animals possessing highly polymorphic genome, our previous research indicated that a specific SNP in chicken Mx gene was responsible for its antiviral function. However, there still has been no information about SNPs in porcine MX2 gene. In this study, we first conducted polymorphism analysis in 17 pigs of MX2 gene derived from seven breeds. Consequently, a total of 30 SNPs, of which 11 were deduced to cause amino acid variations, were detected, suggesting that the porcine MX2 is very polymorphic. Next, we classified MX2 into eight alleles (A1-A8) and subsequently carried out infectious experiments with recombinant VSVDeltaG*-G to each allele. In A1-A5 and A8, position 514 amino acid (514 aa) of MX2 was glycine (Gly), which did not inhibit VSV multiplication, whereas in A6 and A7, 514 aa was arginine (Arg), which exhibited the antiviral ability against VSV. These results demonstrate that a SNP at 514 aa (Gly-Arg) of porcine MX2 plays a pivotal role in the antiviral activity as well as that at 631 aa of chicken Mx. PMID- 24232603 TI - T1 squamous cell carcinoma of the esophagus: long-term outcomes and prognostic factors after esophagectomy. AB - BACKGROUND: Mucosal (T1a) and submucosal (T1b) squamous cell carcinoma of the esophagus (ESCC) have often been analyzed together and are staged as the same category in the UICC/TNM staging system. The difference in surgical outcomes between T1a and T1b ESCC therefore remains unclear. The purpose of this study was to examine the differences in surgical outcomes between T1a and T1b ESCC, and to investigate the prognostic factors in T1 ESCC. METHODS: A prospectively maintained database identified 145 previously untreated patients with pT1 ESCC who underwent radical transthoracic (n = 134) or transhiatal esophagectomy (n = 11). Median follow-up was 108 months. RESULTS: Of the 145 patients, 35 (24 %) had pT1a cancer and 110 (76 %) had pT1b cancer. Lymph node metastasis was present in 45 patients (31 %): 3 patients with pT1a cancer and 42 patients with pT1b cancer (P = 0.0003). The 5-year survival rate for the whole group was 77 %. The 5-year survival rate of the T1a patients was 94 % compared with 72 % for the T1b patients (P = 0.0282). In multivariate analysis, only the depth of tumor invasion (pT1a vs. pT1b) was an independent prognostic factor (hazard ratio 2.358; 95 % confidence interval 1.009-5.513; P = 0.0477). CONCLUSIONS: After esophagectomy, the prognosis of patients with pT1b ESCC is significantly worse than that of patients with pT1a ESCC. Infiltration into the submucosa is the only independent prognostic factor affecting survival. These findings suggested that T1a and T1b ESCC could be staged separately in the next version of UICC/TNM staging system. PMID- 24232604 TI - Protein multilayer architectures on electrodes for anlayte detection. AB - This chapter provides an overview of different assembly methodologies used for the construction of multilayer architectures with biomolecules for application in sensors. Besides the use of bioaffinity interactions and covalent strategies, special attention will be paid to the electrostatic layer-by-layer technique. Different building blocks can be used for the formation of multilayers with a clear preference for polymers and nanoparticles. Among the biomolecules, enzymes and redox proteins are in focus. Because of the high importance of multilayers formed on electrodes, the chapter will concentrate on sensor systems with electrochemical transduction. Particularly advantageous are schemes that can avoid diffusible shuttling molecules between the biomolecule and the electrode and that represent artificial signal chains by exploiting direct protein-protein communication in the immobilized state. PMID- 24232605 TI - Plant regeneration from cytoplasmic hybrids of rice (Oryza sativa L.). AB - We obtained cybrid plants by electrofusing gamma-irradiated protoplasts of a cytoplasmic male-sterile line "A-58 CMS" (Oryza sativa L.) and iodoacetamide (IOA)-treated protoplasts of the fertile (normal) rice cultivar "Fujiminori". The cybridity of the plants was confirmed by mitochondrial (mt) DNA restriction endonuclease, and plasmid-like DNA analyses, and by isozyme, cytological and morphological investigations. The chromosome number of the cybrid plants is 24. PMID- 24232606 TI - Covariance between relatives for X-chromosomal loci in a population in disequilibrium. AB - According to Hardy-Weinberg, for a single autosomal locus, a population achieves equilibrium in one generation of random mating if allelic frequency is the same in the sexes, or in two generations if the frequency is not. For a single X chromosomal locus, however, the approach to equilibrium oscillates and is gradual. Covariances between relatives for autosomal and for X-chromosomal loci are in the literature for a random mating population in equilibrium. Although assumption of equilibrium is defensible for an autosomal locus, it is less defensible for an X-chromosomal locus. Covariances between collateral and between lineal relatives are derived for X-chromosomal loci in a random mating population not in equilibrium. Collateral relatives such as sibs are of the same generation, and lineal relatives such as parent-offspring are of different generations. Coefficient of co-ancestry between relatives, based on identity by descent, was used in this development. Results are applicable to crossbreeding in livestock and poultry, and also to haplo-diploid organisms, such as the honeybee, in which the entire genome is equivalent to being X-chromosomal. PMID- 24232607 TI - A nuclear sequence associated with self-incompatibility in Nicotiana alata has homology with mitochondrial DNA. AB - A 1.0-kb nuclear fragment located 5' to a coding sequence associated with self incompatibility in N. alata shows homology with mitochondrial chromosomal DNA on Southern blots. This sequence is also present in the mitochondrial DNA of two species of tomato, L. esculentum and L. pennellii, but shows no homology to mtDNA of Zea mays. The homologous mitochondrial fragment from N. alata was cloned and sequenced. A short region of 56 bp matches the nuclear sequence in 53/56 bp. Other matched but misaligned segments flank the 3' end. The nuclear sequence is marked at the 5' end by two 8 bp direct repeats. The function of the nuclear sequence is not known although, it is located 397 bp upstream from the site of transcription of the self-incompatibility gene. The mitochondrial sequence contains only limited open reading frames and the nuclear sequence has none. There is evidence that additional segments of the mitochondrial clone hybridize to other nuclear sequences. The exchange of sequences between the mitochondrial and nuclear genomes of plants is discussed. PMID- 24232608 TI - DNA methylation of embryogenic carrot cell cultures and its variations as caused by mutation, differentiation, hormones and hypomethylating drugs. AB - The level of auxin - both natural and synthetic - in the medium has a strong effect on the level of 5-methyl-cytosine in the DNA of carrot cells in culture. This level may vary from approximately 15% to 70% of total cytosine without apparent effects on growth rate and cell morphology. No effect was seen with cytokinin. During somatic embryogenesis, in the absence of hormones, variations were seen in the level of methylation according to a characteristic pattern. If hypomethylation is induced with drugs such as azacytidine, ethionine or ethoxy carbonyl-pyrimidine, embryogenesis is immediately blocked. A mutant was isolated which is resistant to the action of hypomethylating drugs. It shows variations in the methylation pattern and variations in indole-acetic acid metabolism. In addition its regeneration is often associated with the production of tumors. PMID- 24232609 TI - A model of kin-migration in plants. AB - Migrants between plant populations may represent a random sample of the donor population or may be related, being identical in the extreme. There is considerable potential for kin-structured migration in many plant species through the co-dispersal of seeds from single individuals. Through simulation experiments we have shown that the greater the level of relatedness of migrants, the less a given level of migration counterbalances the effect of genetic drift among populations. PMID- 24232610 TI - Minicircle variation in Beta mitochondrial DNA. AB - Mitochondrial DNAs from nine male fertile and eight cytoplasmic male sterile (cms) accessions of wild and cultivated Beta beets were investigated for the presence of low molecular weight DNA molecules. Five different supercoiled DNA molecules were detected, varying in size from 1.33 to 1.63 kb. Southern hybridizations revealed multimeric forms and sequence homologies between the minicircles. The occurrence of the different minicircles among the 17 accessions was investigated by agarose gel electrophoresis and Southern hybridization using minicircle specific probes. The 1.33 and 1.63 kb minicircles were found in most accessions, the other three minicircles were found in one or two of the wild Beta beet accessions. The presence of a low number of small, more or less homologous, minicircles in all investigated plants makes these molecules a general characteristic of Beta mtDNA. No association is found between the presence or absence of specific minicircles and the expression of male sterility. Neither does the distribution of the different minicircles in Beta beets indicate any essential biological role of these minicircles. PMID- 24232611 TI - Karyotype analysis of regenerated plants from callus cultures of interspecific hybrids of cultivated barley (Hordeum vulgare L.). AB - The karyotype of 82 regenerated plants from callus cultures of interspecific hybrids between cultivated barley (Hordeum vulgare L.) and seven polyploid wild barley species was examined by C-banding or Feulgen staining. The karyotypic changes observed in 46 plants included aneuploidy, double haploidy, amphidiploidy, deletions, inversions, extra C-bands, and extra euchromatic segments. Apparently, chromosome 5, 6, and 7 of H. vulgare were more frequently exposed to elimination or structural change than the other chromosomes of this species. Irradiation of calli seemed to enhance the occurrence of karyotypic variants. PMID- 24232612 TI - RFLP analysis of the size of chromosomal segments retained around the Tm-2 locus of tomato during backcross breeding. AB - Genes introduced into cultivated plants by backcross breeding programs are flanked by introgressed segments of DNA derived from the donor parent. This phenomenon is known as linkage drag and is frequently thought to affect traits other than the one originally targeted. The Tm-2 gene of Lycopersicon peruvianum, which confers resistance to tobacco mosaic virus, was introduced into several different tomato cultivars (L. esculentum) by repeated backcrossing. We have measured the sizes of the introgressed segments flanking the Tm-2 locus in several of these cultivars using a high density map of restriction fragment length polymorphic (RFLP) markers. The smallest introgressed segment is estimated to be 4 cM in length, while the longest is over 51 cM in length and contains the entire short arm of chromosome 9. Additionally, RFLP analysis was performed on remnant seed from different intermediate generations corresponding to two different backcross breeding programs for TMV resistance. The results reveal that plants containing desirable recombination near the resistance gene were rarely selected during backcrossing and, as a result, the backcross breeding method was largely ineffective in reducing the size of linked DNA around the resistance gene. We propose that, by monitoring recombination around genes of interest with linked RFLP markers, one can quickly and efficiently reduce the amount of linkage drag associated with introgression. Using such a procedure, it is estimated that an introgressed segment can be obtained in two generations that is as small as that which would otherwise require 100 backcross generations without RFLP selection. PMID- 24232613 TI - An isoenzyme study in the genus Lotus (Fabaceae) : Segregation of isoenzyme alleles in synthetic allo- and autotetraploids, and in L. corniculatus. AB - Segregation of the cytosolic Pgi2 locus was studied among progeny of the synthetic allotetraploid (L. japonicus * L. alpinus)(2), the synthetic autotetraploid (L. alpinus)(2), and the cultivated tetraploid species L. corniculatus L. Evidence of an original diploid duplication found within the interspecific hybrid L. japonicus * L. alpinus was also found within the synthetic allotetraploid (quadruplication of loci). Evidence suggesting quadruplication of loci was also found in the tetraploid L. corniculatus, but not in the synthetic autotetraploid (L. alpinus)(2). It is suggested that the original duplication resulted from unequal crossing-over between homoeologues and that it provides evidence that L. corniculatus is a segmental allotetraploid. Quadruplication of loci in L. corniculatus could explain previously reported distorted tetrasomic ratios for segregation of qualitative characters in this species. PMID- 24232614 TI - Response of wheatgrasses and wheat * wheatgrass hybrids to barley yellow dwarf virus. AB - Resistance to barley yellow dwarf virus (BYDV), manifested by low enzyme-linked immunosorbent assay (ELISA) values in plants exposed to viruliferous aphids, was identified in several wheatgrasses (Agropyron spp.). ELISA results were similar for root and leaf extracts of infested plants. No difference in reaction to BYDV was found between plants grown in the field and those in the growth chamber. Interspecific hybrids were generated using pollen from single resistant plants of Agropyron spp. to pollinate soft red winter wheat spikes. Resistance in hybrids appeared to be at the level of virus replication rather than at the level of vector inoculation. The hybrids varied in their reaction to BYDV. Expression of BYDV resistance in hybrids was influenced not only by wheat genotype and Agropyron species but, in some cases, reaction varied even among hybrids between the same wheat genotype and Agropyron plant. Implications of these results are discussed. PMID- 24232615 TI - Quantitatively determined self-incompatibility : 1. Theoretical considerations. AB - It has been reported that incomplete self-incompatibility could be determined in Borago officinalis by many genes. Simple ten-gene models for such enforced cross fertilization have been developed and their properties examined by computer simulation. Mutation rates necessary to maintain a given level of variability in small populations are high, as already determined theoretically for oligogenic self-incompatibility systems. However, the extent of ineffective pollination is very much greater in the ten-gene system. This finding may be verifiable in borage if it is indeed self-incompatible. PMID- 24232616 TI - Restriction endonuclease analysis of mitochondrial DNA from sorghum with fertile and male-sterile cytoplasms. AB - Mitochondrial DNA from four paired (fertile and male-sterile) lines and six isocytoplasmic strains of sorghum (Sorghum bicolor (L.) Moench) were fragmented by endonucleases and their electrophoretic patterns were examined. Cytoplasmic male sterile lines differed from their male-fertile counterparts consistently. Among the isocytoplasmic strains, KS 36A (S. verticilli-florum cytoplasm), KS 38A (S. conspicum cytoplasm), and KS 39A (S. niloticum cytoplasm) showed minor differences from the other strains. Results suggest that restriction endonuclease patterns are useful in detecting differences in mitochondrial genomes. PMID- 24232617 TI - Molecular characterization of Mutator systems in maize embryogenic callus cultures indicates Mu element activity in vitro. AB - Active Mutator lines of maize (Zea mays L.) are characterized by their ability to generate new mutants at a high rate and by somatic instability at Mutator-induced mutant alleles. Mutagenically active lines with fewer than ten Mu elements per diploid genome have not been observed. Alteration of Mutator activity has been shown to correlate with the state of modification of Hinfl restiction sites that lie within inverted terminal repeats of Mu elements. To determine whether active Mutator systems can be established and maintained in culture, copy number and modification state of Mu elements were investigated in embryogenic callus lines derived from F1S of crosses of active Mutator stock with the inbred lines A188 and H99. All callus lines studied maintain high Mu-element copy numbers, and more than half show a continued lack of modification at the Mu element Hinfl sites; thus, parameters associated with mutagenic activity in planta are present in some, but not all, callus lines. Mutator activity was then tested directly by restriction fragment analysis of subclonal populations from A188/Mu (2) and H99/Mu (2) embryonic cultures. Novel Mu-homologous restriction fragments occurred in 38% of the subpopulations which contained unmodified Mu elements, but not in control cultures containing modified, genetically inactive Mu elements. We conclude that Mu elements from active Mutator parents can remain transpositionally active in embryogenic cell culture. Active Mutator cell lines may be useful for the production of mutations in vitro. PMID- 24232618 TI - Linkages between restriction fragment length, isozyme, and morphological markers in lentil. AB - A genetic linkage map of lentil comprising 333 centimorgans (cM) was constructed from 20 restriction fragment length, 8 isozyme, and 6 morphological markers segregating in a single interspecific cross (Lens culinaris * L. orientalis). Because the genotypes at marker loci were determined for about 66 F2 plants, linkages are only reported for estimates of recombination less than 30 cM. Probes for identification of restriction fragment length polymorphisms (RFLPs) were isolated from a cDNA and EcoRI and PstI partial genomic libraries of lentil. The cDNA library gave the highest frequency of relatively low-copy-number probes. The cDNAs were about twice as efficient, relative to random genomic fragments, in RFLP detection per probe. Nine markers showed significant deviations from the expected F2 ratios and tended to show a predominance of alleles from the cultigen. Assuming a genome size of 10 Morgans, 50% of the lentil genome could be linked within 10 cM of the 34 markers and the map is of sufficient size to attempt mapping of quantitative trait loci. PMID- 24232619 TI - Evaluation of three test statistics used to identify maize inbred lines with new favorable alleles not present in elite single cross. AB - The identification of inbred lines useful for improvement of an elite single cross hybrid is an essential part of a pedigree maize (Zea mays L.) breeding program. The objectives of this study were to identify lines that could be useful for improvement of hybrid B73 * Mo17 and to relate the values of estimators of new favorable alleles with test cross yields. Crosses of parents of hybrid B73 * Mo17 with 10 public lines from the United States (US), and 14 Maize Research Institute "Zemun Polje" proprietary lines (lines per se, and test crosses from 3 F2 populations) were evaluated at 4 locations in Yugoslavia in 1986. Significant differences in grain yield were found among lines in minimally biased estimates of favorable alleles (MUG) present in a donor inbred but not present in a B73 * Mo17, in minimum upper bound (UBND) estimates and in predicted three-way performance (PTC). Twenty-one lines had a significant number of dominant favorable alleles for grain yield not present in B73 * Mo17. The highest values for all estimators of new favorable alleles were found for donor lines which belonged to different heterotic groups than the B73 and Mo17. For most of the inbreds, the (C + F) - (D + E) statistics agreed with predigree information. Simultaneous increases in grain yield and decreases in grain moisture content for B73 * Mo17 are possible with several donor inbred lines. All of the lines with a high number of new favorable alleles for grain yield not present in B73 * Mo17 had negative MUD (F)-MUG values for low plant height. Line N152 had the most new favorable alleles for grain yield not present in single cross B73 * Mo17. Population (N152 * Mo17) F2 had the highest difference of observed test cross means from check mean, the most test crosses with significantly higher yields than the check, and the largest estimate of number of segregating loci. PMID- 24232620 TI - Directional selection in lines founded from different parts of the phenotypic distribution of sternopleural chaetae number in Drosophila melanogaster. AB - Divergent directional selection lines were initiated from base populations founded from parents taken from different parts of the sternopleural chaetae distribution in a cage population of Drosophila melanogaster. Lines founded from parents taken from the central part of the distribution showed greater response and higher realised heritability than lines derived from parents with extreme high or extreme low chaetae number. The results suggest that centrally derived phenotypes have higher heterozygosity for chaetae factors than extreme phenotypes and that these factors have a large effect on the character. PMID- 24232621 TI - Mutational variance for pupa weight in Tribolium castaneum. AB - Directional selection for heavier pupa weight in Tribolium castaneum was practiced for 18 generations in two replicates of an inbred line, each separately maintained in small population cages for more than 90 generations. Mutational variance was estimated in two ways, based on Hill's (1982a) prediction equation for response to directional selection where an equilibrium state between effective population size and variation created by new mutation is assumed. Estimates of mutational variance based on response to selection in a selected population and from a sire-offspring regression analysis in an unselected control population were in strong agreement within each replicate population. Significant differences between the two replicates were observed. Estimates of the ratio of mutational variance to environmental variance ranged from 0.0002 to 0.0012, depending upon the assumptions made about effective population sizes maintained in the two replicate lines. Estimates of realized heritability from the 18 generations of selection were 0.23+/-0.02 and 0.12+/-0.02 in the two replicates. The results support the hypothesis that mutation may have played a significant role in supplying useful genetic variation for long-continuing response to selection for this trait in experiments reported earlier. PMID- 24232622 TI - Genetic diversity of wild emmer wheat in Israel and Turkey : Structure, evolution, and application in breeding. AB - Allozyme variation in the tetraploid wild emmer wheat, Triticum dicoccoides, the progenitor of all cultivated wheats, was studied for the proteins encoded by 42 gene loci in 1815 plants representing 37 populations - 33 from Israel and 4 from Turkey - sampled in 33 localities from 1979 to 1987. The results showed that: (a) 6 loci (14%) were monomorphic in all populations, 15 loci (36%) were locally polymorphic, and 21 loci (50%) were regionally polymorphic. These results are similar to those obtained earlier on 12 Israeli populations. All polymorphic loci (except 4) displayed high local levels of polymorphism (>/ 10%). (b) The mean number of alleles per locus, A, was 1.252 (range: 1.050-1.634); the proportion of polymorphic loci per population averaged 0.220 (range: 0.050-0.415); genic diversity, He, averaged 0.059 (range: 0.002-0.119). (c) Altogether there were 119 alleles at the 42 putative loci tested, 114 of these in Israel, (d) Genetic differentiation was primarily regional and local, not clinal; 70% of the variant alleles were common (>/ 10%) and not widespread, but rather localized or sporadic, displaying an "archipelago" population genetics and ecology structure. The coefficients of genetic distance between populations were high and averaged D = 0.134; range: 0.018-0.297, an indication of sharp genetic differentiation over short distances, (e) Discriminant analyses differentiated Israeli from Turkish populations, and within Israel, between central and 3 marginal regions, as well as between different soil-type populations, (f) Allozymic variation comprised 40% within and 60% between populations, (g) Gametic phase disequilibria were abundant, their number being positively correlated (rs = 0.60, P<0.01) with the humidity, (h) Multilocus organization was substantive, also positively correlated with humidity, (i) Allozyme diversity, overall and at single loci, was significantly correlated with, and partly predictable by, climatic and edaphic factors, (j) The distrubition of the significant positive and negative values and the absence of autocorrelations in the correlogram revealed no similar geographic patterns across loci, eliminating migration as a prime factor of population genetic differentiation. These results suggest: (I) during the evolutionary history of wild emmer, diversifying natural selection, through climatic and edaphic factors, was a major agent of genetic structure and differentiation at both the single and multilocus levels; (II) wild emmer harbors large amounts of genetic diversity exploitable as genetic markers in sampling and abundant genetic resources utilizable for wheat improvement. PMID- 24232623 TI - A fully-asynchronous low-power implantable seizure detector for self-triggering treatment. AB - In this paper, we present a new asynchronous seizure detector that is part of an implantable integrated device intended to identify electrographic seizure onset and trigger a focal treatment to block the seizure progression. The proposed system has a low-power front-end bioamplifier and a seizure detector with intelligent mechanism to reduce power dissipation. This system eliminates the unnecessary clock gating during normal neural activity monitoring mode and reduces power dissipation in the seizure detector; as a result, this device is suitable for long-term implantable applications. The proposed system includes analog and digital building blocks with programmable parameters for extracting electrographic seizure onset information from real-time EEG recordings. Sensitivity of the detector is enhanced by optimizing the variable parameters based on specific electrographic seizure onset activities of each patient. The detection algorithm was validated using Matlab tools and implemented in standard 0.13 MUm CMOS process with total die area of 1.5 * 1.5 mm2. The fabricated chip is validated offline using intracranial EEG recordings from two patients with refractory epilepsy. Total power consumption of the chip is 9 MUW and average detection delay is 13.7 s after seizure onset, well before the onset of clinical manifestation. The proposed system achieves an accurate detection performance with 100% sensitivity and no false alarms during the analyses of 15 seizures and 19 non-seizure datasets. PMID- 24232624 TI - A 155 MU W 88-dB DR discrete-time ?Sigma modulator for digital hearing aids exploiting a summing SAR ADC quantizer. AB - This paper presents a low-power switched-capacitor ?Sigma modulator for digital hearing-aid applications that features a novel summing successive approximation (SAR). The summing SAR performs multi-bit quantization together with the analog addition required in feed-forward (FF) ?Sigma modulator (?SigmaM) topologies, with no attenuation of the input signals and no need for amplifiers. The prototype is implemented in a 0.18- MU m CMOS technology and its measurements demonstrate a dynamic range of 88 dB in 10 kHz bandwidth while consuming 155 MUW from a 1.8 V supply. The combined use of passive addition and SAR quantization reduces the complexity and power consumption of the modulator. The summing SAR ADC quantizer results in a calculated power saving of 40% when compared to a multi-bit FF ?SigmaM using active addition and flash quantization. PMID- 24232625 TI - CMOS spectrally-multiplexed FRET-on-a-chip for DNA analysis. AB - A spectral-multiplexed fluorescence contact imaging microsystem for DNA analysis is presented. The microsystem integrates a filterless CMOS Color PhotoGate (CPG) sensor that exploits the polysilicon gate as an optical filter, and therefore does not require an external color filter. The CPG is applied to fluorescence based transduction in a spectrally multiplexed format by differentiating among multiple emission bands, hence replacing the functionality of a bank of emission filters. A microsystem has been quantitatively modeled and prototyped based on the CPG fabricated in a standard 0.35 MUm CMOS technology. The multi-color imaging capability of the microsystem in analyzing DNA targets has been validated in the detection of marker gene sequences for spinal muscular atropy disease and Escherichia coli (E. coli). Spectral-multiplexing enables the two DNA targets to be simultaneously detected with a measured detection limits of 240 nM and 210 nM for the two target concentrations at a sample volume of 10 MUL for the green and red transduction channels, respectively. PMID- 24232626 TI - Camera phone-based quantitative analysis of C-reactive protein ELISA. AB - We demonstrate the use of a camera phone as a low-cost optical detector for quantitative analysis of a high-sensitivity C-reactive protein (hs-CRP) enzyme linked immunosorbent assay (ELISA). The camera phone was used to acquire images of the ELISA carried out in a conventional 96 well plate. Colorimetric analysis of the images was used to determine a standard curve that exhibited excellent agreement with a fitted 4-parameter logistic model (R2=0.998). The limit of detection (LOD) for this approach was determined to be 0.026 +/- 0.002 MUg/ml (1.035 +/- 0.079 MUM) CRP. Furthermore, these results were found to be in very close agreement with measurements obtained for the same assay using a laboratory based instrument. These findings indicate the basic technology to enable low-cost quantitative home-based monitoring of an important clinical biomarker of inflammatory disease may already be present in the patient's home. PMID- 24232627 TI - A 0.18 MUm biosensor front-end based on 1/f noise, distortion cancelation and chopper stabilization techniques. AB - This paper presents a novel sensor front-end circuit that addresses the issues of 1/f noise and distortion in a unique way by using canceling techniques. The proposed front-end is a fully differential transimpedance amplifier (TIA) targeted for current mode electrochemical biosensing applications. In this paper, we discuss the architecture of this canceling based front-end and the optimization methods followed for achieving low noise, low distortion performance at minimum current consumption are presented. To validate the employed canceling based front-end, it has been realized in a 0.18 MUm CMOS process and the characterization results are presented. The front-end has also been tested as part of a complete wireless sensing system and the cyclic voltammetry (CV) test results from electrochemical sensors are provided. Overall current consumption in the front-end is 50 MUA while operating on a 1.8 V supply. PMID- 24232628 TI - Capacitive-coupling-based information transmission system for implantable devices: investigation of transmission mechanism. AB - Many medical electronic devices that can be implanted deep inside the body have been developed recently. These devices are designed to transmit the information that is collected inside the body to receiving antennas outside the body. In this work, we examine a method that uses a high-frequency current in the transmitting electrodes of the implanted device for the transmission of information to receiving electrodes attached to the body surface. To investigate the transmission mechanism and the factors that determines the optimum frequency, the output voltage V2 and the input and output impedance ( Zin and Zout) were analyzed by conducting a finite-difference time-domain electromagnetic simulation. The results clearly show that the receiving part (electrodes and wire), including biological tissue, acts as a loop antenna. The maximum V2 value was obtained at the first parallel resonance frequency of Zout at 370 MHz under a load resistance of 1 MOmega. In contrast, the output current of the source increased at the series resonance frequency of Zin. The series resonance frequency could be adjusted to move a target frequency by adding an inductance between the source and the transmitting electrodes. PMID- 24232629 TI - Impedance measurement system for determination of capacitive electrode coupling. AB - Capacitive electrodes have been studied as an alternative to gel electrodes, as they allow measurement of biopotentials without conductive contact with the patient. However, because the skin interface is not as precisely defined as with gel electrodes, this could lead to signal deformation and misdiagnoses. Thus, measurement of a capacitive coupling of the electrodes may allow to draw conclusions about the applicability of such systems. In addition, combining capacitive biosignal sensing with an impedance measurement unit may enable bioimpedance measurements, from which additional information on the hydration status can be extracted. A prototype system is introduced which measures impedance over capacitive electrodes in parallel with biopotential measurements. Also presented are the first results on characterization of the skin electrode coupling achieved with the system. PMID- 24232630 TI - 15-nW Biopotential LPFs in 0.35- MUm CMOS using subthreshold-source-follower Biquads with and without gain compensation. AB - Most biopotential readout front-ends rely on the g m- C lowpass filter (LPF) for forefront signal conditioning. A small g m realizes a large time constant ( tau = C / g m) suitable for ultra-low-cutoff filtering, saving both power and area. Yet, the noise and linearity can be compromised, given that each g m cell can involve one or several noisy and nonlinear V- I conversions originated from the active devices. This paper proposes the subthreshold-source-follower (SSF) Biquad as a prospective alternative. It features: 1) a very small number of active devices reducing the noise and nonlinearity footsteps; 2) No explicit feedback in differential implementation, and 3) extension of filter order by cascading. This paper presents an in-depth treatment of SSF Biquad in the nW-power regime, analyzing its power and area tradeoffs with gain, linearity and noise. A gain compensation (GC) scheme addressing the gain-loss problem of NMOS-based SSF Biquad due to the body effect is also proposed. Two 100-Hz 4th-order Butterworth LPFs using the SSF Biquads with and without GC were fabricated in 0.35- MUm CMOS. Measurement results show that the non-GC (GC) LPF can achieve a DC gain of -3.7 dB (0 dB), an input-referred noise of 36 MUV rms (29 MUV rms ), a HD3@60 Hz of 55.2 dB ( - 60.7 dB) and a die size of 0.11 mm2 (0.08 mm2). Both LPFs draw 15 nW at 3 V. The achieved figure-of-merits (FoMs) are favorably comparable with the state-of-the-art. PMID- 24232631 TI - A highly linear fully integrated powerline filter for biopotential acquisition systems. AB - Powerline interference is one of the most dominant problems in detection and processing of biopotential signals. This work presents a new fully integrated notch filter exhibiting high linearity and low power consumption. High filter linearity is preserved utilizing active-RC approach while IC implementation is achieved through replacing passive resistors by R-2R ladders achieving area saving of approximately 120 times. The filter design is optimized for low power operation using an efficient circuit topology and an ultra-low power operational amplifier. Fully differential implementation of the proposed filter shows notch depth of 43 dB (78 dB for 4th-order) with THD of better than -70 dB while consuming about 150 nW from 1.5 V supply. PMID- 24232632 TI - Simultaneous neural and movement recording in large-scale immersive virtual environments. AB - Virtual reality (VR) allows precise control and manipulation of rich, dynamic stimuli that, when coupled with on-line motion capture and neural monitoring, can provide a powerful means both of understanding brain behavioral relations in the high dimensional world and of assessing and treating a variety of neural disorders. Here we present a system that combines state-of-the-art, fully immersive, 3D, multi-modal VR with temporally aligned electroencephalographic (EEG) recordings. The VR system is dynamic and interactive across visual, auditory, and haptic interactions, providing sight, sound, touch, and force. Crucially, it does so with simultaneous EEG recordings while subjects actively move about a 20 * 20 ft2 space. The overall end-to-end latency between real movement and its simulated movement in the VR is approximately 40 ms. Spatial precision of the various devices is on the order of millimeters. The temporal alignment with the neural recordings is accurate to within approximately 1 ms. This powerful combination of systems opens up a new window into brain-behavioral relations and a new means of assessment and rehabilitation of individuals with motor and other disorders. PMID- 24232633 TI - A 1.5 ns OFF/ON switching-time voltage-mode LVDS driver/receiver pair for asynchronous AER bit-serial chip grid links with up to 40 times event-rate dependent power savings. AB - This paper presents a low power fast ON/OFF switchable voltage mode implementation of a driver/receiver pair intended to be used in high speed bit serial Low Voltage Differential Signaling (LVDS) Address Event Representation (AER) chip grids, where short (like 32-bit) sparse data packages are transmitted. Voltage-Mode drivers require intrinsically half the power of their Current-Mode counterparts and do not require Common-Mode Voltage Control. However, for fast ON/OFF switching a special high-speed voltage regulator is required which needs to be kept ON during data pauses, and hence its power consumption must be minimized, resulting in tight design constraints. A proof-of-concept chip test prototype has been designed and fabricated in low-cost standard 0.35 MU m CMOS. At +/- 500 mV voltage swing with 500 Mbps serial bit rate and 32 bit events, current consumption scales from 15.9 mA (7.7 mA for the driver and 8.2 mA for the receiver) at 10 Mevent/s rate to 406 MU A ( 343 MU A for the driver and 62.5 MUA for the receiver) for an event rate below 10 Kevent/s, therefore achieving a rate dependent power saving of up to 40 times, while keeping switching times at 1.5 ns. Maximum achievable event rate was 13.7 Meps at 638 Mbps serial bit rate. Additionally, differential voltage swing is tunable, thus allowing further power reductions. PMID- 24232634 TI - Postnatal early overnutrition causes long-term renal decline in aging male rats. AB - BACKGROUND: We evaluated the influence of postnatal early overnutrition on renal pathophysiological changes in aging rats. METHODS: Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (control) groups, respectively, during the first 21 d of life. The effects of early postnatal overnutrition were determined at 12 mo. RESULTS: SL rats weighed more than controls between 4 d and 6 mo of age (P < 0.05). However, between 6 and 12 mo, body weights in both groups were not different. In the SL group, at 12 mo, systolic blood pressure was higher and creatinine clearance was lower than the same in controls (P < 0.05). Numbers of CD68 (ED1)-positive macrophages and apoptotic cells in renal cortex were higher in SL rats (P < 0.05). Furthermore, index scores for glomerulosclerosis and tubulointerstitial fibrosis were higher in the SL group (P < 0.05). Significantly less glomeruli per section area were found in aging SL rats (P < 0.05). Immunoblotting and immunohistochemistry showed decreased intrarenal renin expression in SL rats (P < 0.05). CONCLUSION: Early postnatal overnutrition can potentiate structural and functional abnormalities in the aging kidney and can lead to systolic hypertension with reduced intrarenal renin activity. PMID- 24232635 TI - Altered canonical Wingless-Int signaling in the ovine fetal lung after exposure to intra-amniotic lipopolysaccharide and antenatal betamethasone. AB - BACKGROUND: Antenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-Int (Wnt) signaling directs lung development and repair. We showed that intra-amniotic (IA) lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs. Therefore, we hypothesized that pulmonary Wnt signaling was altered by exposure to IA LPS and/or antenatal corticosteroids. METHODS: Ovine fetuses were exposed to IA LPS, maternal intramuscular betamethasone, a control saline injection, or a combination thereof at 107 and/or 114 d gestational age (term = 150 d gestational age) before delivery at 121 d gestational age. RESULTS: IA LPS exposure decreased the lung expression of lymphoid enhancer-binding factor 1 (LEF1), a major Wnt pathway effector. WNT1, WNT4, and downstream messenger beta-catenin decreased after LPS exposure. WNT7b mRNA increased fourfold 14 d post-LPS exposure. Betamethasone treatment 7 d before LPS exposure prevented the reduction in LEF1 expression, whereas betamethasone administration after LPS normalized the LPS-induced increase in Wnt7b mRNA. CONCLUSION: IA LPS exposure decreased canonical Wnt signaling in the developing lung. Antenatal corticosteroids before or after IA inflammation had different effects on pulmonary Wnt signaling. This study provides new insights into possible mechanisms by which prenatal inflammation affects lung development and how corticosteroid can be beneficial in this setting. PMID- 24232636 TI - Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells. AB - BACKGROUND: Children born to mothers with gestational diabetes mellitus (GDM) experience increased risk of developing hypertension, type 2 diabetes mellitus, and obesity. Disrupted function of endothelial colony-forming cells (ECFCs) may contribute to this enhanced risk. The goal of this study was to determine whether cord blood ECFCs from GDM pregnancies exhibit altered functionality. METHODS: ECFCs isolated from the cord blood of control and GDM pregnancies were assessed for proliferation, senescence, and Matrigel network formation. The requirement for p38MAPK in hyperglycemia-induced senescence was determined using inhibition and overexpression studies. RESULTS: GDM-exposed ECFCs were more proliferative than control ECFCs. However, GDM-exposed ECFCs exhibited decreased network forming ability in Matrigel. Aging of ECFCs by serial passaging led to increased senescence and reduced proliferation of GDM-exposed ECFCs. ECFCs from GDM pregnancies were resistant to hyperglycemia-induced senescence compared with those from controls. In response to hyperglycemia, control ECFCs activated p38MAPK, which was required for hyperglycemia-induced senescence. In contrast, GDM-exposed ECFCs showed no change in p38MAPK activation under equivalent conditions. CONCLUSION: Intrauterine exposure of ECFCs to GDM induces unique phenotypic alterations. The resistance of GDM-exposed ECFCs to hyperglycemia induced senescence and decreased p38MAPK activation suggest that these progenitor cells have undergone changes that induce tolerance to a hyperglycemic environment. PMID- 24232637 TI - Ingested soluble CD14 from milk is transferred intact into the blood of newborn rats. AB - BACKGROUND: Milk acts as an edible immune system that is transferred from mother to newborn. Soluble Cluster of Differentiation 14 (sCD14) is a protein found in significant quantities in human milk (~8-29 ug/ml). At a 10-fold lower concentration in the blood (~3 ug/ml), the most notable role of sCD14 is to sequester lipopolysaccharides of Gram-negative bacteria from immune cells. METHODS: To explore the pharmacodynamics of this milk protein and its biological fate, the biodistribution of radiolabeled sCD14 ((14)C, (125)I) was monitored in 10-d-old rat pups. RESULTS: Up to 3.4 +/- 2.2% of the radiolabeled sCD14 administered was observed, intact, in the pup blood for up to 8 h post-ingestion. Additionally, 30.3 +/- 13.0% of the radiolabeled sCD14 administered was observed degraded in the stomach at 8 h post-ingestion. A reservoir of intact, administered sCD14 (3.2 +/- 0.3%), however, remained in the stomach at 8 h post ingestion. Intact sCD14 was observed in the small intestine at 5.5 +/- 1.6% of the dose fed at 8 h post-ingestion. CONCLUSION: The presence of intact sCD14 in the blood and the gastrointestinal tract of newborns post-ingestion has implications in the development of allergies, obesity, and other inflammation related pathogeneses later in life. PMID- 24232638 TI - Effect of obesity intervention programs on adipokines, insulin resistance, lipid profile, and low-grade inflammation in 3- to 5-y-old children. AB - BACKGROUND: Childhood obesity can cause the development of cardiovascular risk factors. We assessed the effect of a multidisciplinary intervention program on cardiovascular risk factors and compared this effect with a usual-care program in 3- to 5-y-old overweight or obese children. METHODS: Seventy-five children were randomly assigned to a multidisciplinary intervention or a usual-care program. Anthropometry, body composition, and abdominal adipose tissue were assessed at the start and end of a 16-wk program. Concurrently, fasting concentrations of serum lipids, glucose, insulin, HbA1c, leptin, adiponectin, high-sensitive C reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, and interleukin (IL) 6 were determined. RESULTS: In both groups, insulin sensitivity improved, demonstrated by decreased insulin concentrations and a decreased HOMA2-IR. In the multidisciplinary intervention group, there was also a decrease of HbA1c and TNF alpha. In the usual-care group, an increase in glucose concentrations was found. Comparing both groups, changes over time were not different, besides trends in the decrease in total cholesterol and TNF-alpha, in favor of the multidisciplinary intervention group. Combining the results of both groups, a correlation was found between the decrease in body fat percentage (BF%), and both HOMA2-IR and triglyceride (TG) concentrations. CONCLUSION: In 3- to 5-y-old children, both obesity intervention programs improved insulin sensitivity, in parallel with a reduced BF%. PMID- 24232639 TI - Exploration of novel predictive markers in rat plasma of the early stages of chronic renal failure. AB - To identify blood markers for early stages of chronic kidney disease (CKD), blood samples were collected from rats with adenine-induced CKD over 28 days. Plasma samples were subjected to metabolomic profiling by liquid chromatography-mass spectrometry, followed by multivariate analyses. In addition to already identified uremic toxins, we found that plasma concentrations of N6-succinyl adenosine, lysophosphatidylethanolamine 20:4, and glycocholic acid were altered, and that these changes during early CKD were more sensitive markers than creatinine concentration, a universal indicator of renal dysfunction. Moreover, the increase in plasma indoxyl sulfate concentration occurred earlier than increases in phenyl sulfate and p-cresol sulfate. These novel metabolites may serve as biomarkers in identifying early stage CKD. PMID- 24232640 TI - Analysis of storage proteins in normal and aborted seeds from embryo-lethal mutants of Arabidopsis thaliana. AB - The major storage proteins isolated from wild-type seeds of Arabidopsis thaliana (L.) Heynh., strain "Columbia", were studied by sucrose gradient centrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Both the hypocotyl and cotyledons of mature embryos contained abundant 12 S (cruciferin) and 2 S (arabin) proteins that appeared similar in size and subunit composition to the cruciferin (12 S) and napin (1.7 S) seed-storage proteins of Brassica napus. The 12 S protein from Arabidopsis was resolved by SDS-PAGE into two groups of subunits with approximate relative molecular weights of 22-23 kDa (kilodalton) and 30-34 kDa. These polypeptides accumulated late in embryo development, disappeared early in germination, and were not detected in other vegetative or reproductive tissues. Accumulation of the 12 S proteins in aborted seeds from nine embryo-lethal mutants with different patterns of abnormal development was studied to determine the extent of cellular differentiation in arrested embryos from each mutant line. Abundant 12 S proteins were found in arrested embryos from two mutants with late lethal phases, but not in seven other mutants with lethal phases ranging from the globular to the cotyledon stages of embryo development. These results indicate that the accumulation of seed-storage proteins in wild-type embryos of Arabidopsis is closely tied to morphogenetic changes that occur during embryo development. Embryo-lethal mutants may therefore be useful in future studies on the developmental regulation of storage-protein synthesis. PMID- 24232641 TI - Fatty-acid composition of polar lipids in fruit and leaf chloroplasts of "16:3"- and "18:3"-plant species. AB - The fatty-acid composition of polar lipids from fruit and leaf chloroplasts was compared in five Solanaceous and two cucurbit species. The acylated fatty acids in monogalactosyl diglycerides (MGDG) from leaf chloroplasts of all five Solanaceous species included substantial amounts of Delta (7,10,13) hexadecatrienoic acid (16:3). In contrast, the MGDG from fruit chloroplasts of the Solanaceae contained very little of this plastid-specific polyunsaturate, and instead included a proportionately greater percentage of linoleic acid (18:2). In MGDG from leaf chloroplasts of two cucurbits, alpha-linolenic acid (18:3) constituted 94-95% of the acylated fatty acids. Fruit-chloroplast galactolipids of the cucurbits had a greater abundance of 18:2, and hence a higher 18:2/18:3 ratio, than found in the corresponding leaf lipids. Among the phosphoglycerides, the unusual fatty acid Delta3-trans-hexadecenoate (trans-16:1) constituted from 15 to 24% of the acylated fatty acids in phosphatidyl glycerol (PG) from leaf chloroplasts (all species). In sharp contrast, trans-16:1 was virtually absent in PG from fruit chloroplasts of both Solanaceous and cucurbit species, and was replaced by a proportionate increase in the content of palmitate (16:0). The observed differences in the polar lipid fatty-acid composition of fruit and leaf chloroplasts are discussed in terms of the relative activity of several intrachloroplastic enzymes involved in lipid synthesis and fatty-acyl desaturation. PMID- 24232642 TI - Isotopic relationships between saponifiable lipids and cellulose nitrate prepared from red, brown and green algae. AB - Stable carbon and hydrogen isotope ratios were determined for the saponifiable lipid fraction as well as the cellulose fraction (the latter after nitration to remove exchangeable hydrogens) of several species of red, brown and green algae from three locations. A significant correlation was observed between the hydrogen isotope ratios of cellulose nitrate and saponifiable lipid for red algae, but not for brown or green algae. Carbon-13/carbon-12 ratios for both fractions of red algae were in general lower than those observed for brown and green algae. The results reported here are consistent with the proposals that red algae evolved much earlier than and are metabolically different from the brown and green algae. PMID- 24232643 TI - In-situ Raman microprobe studies of plant cell walls: Macromolecular organization and compositional variability in the secondary wall of Picea mariana (Mill.) B.S.P. AB - Native-state organization and distribution of cell-wall components in the secondary wall of woody tissue from P. mariana (Black Spruce) have been investigated using polarized Raman microspectroscopy. Evidence for orientation is detected through Raman intensity variations resulting from rotations of the exciting electric vector with respect to cell-wall geometry. Spectral features associated with cellulose and lignin were studied. The changes in cellulose bands indicate that the pyranose rings of the anhydroglucose repeat units are in planes perpendicular to the cross section, while methine C-H bonds are in planes parallel to the cross section. Changes in bands associated with lignin indicate that the aromatic rings of the phenyl-propane units are most often in the plane of the cell-wall surface. However, regions where lignin orientation departs from this pattern also occur. These results represent direct evidence of molecular organization with respect to cellular morphological features in woody tissue, and indicate that cell-wall components are more highly organized than had been recognized. Studies carried out in order to establish the usefulness and sensitivity of the Raman technique to differences of composition within the cell walls provide evidence of variations in the distribution of cellulose and lignin. Such compositional differences were more prominent between the walls of different cells than within a particular cell wall. PMID- 24232644 TI - beta-Mannoside mannohydrolase and the mobilization of the endosperm cell wall of lettuce seeds, cv. Grand Rapids. AB - Mobilization of the endosperm cell-wall reserves of Lactuca sativa L. cv. Grand Rapids requires endo-beta-mannanase and alpha-galactosidase activity. A third enzyme, beta-mannoside mannohydrolase (EC 3.2.1.25) is also involved. We have determined the optimum extraction and assay conditions for this enzyme, which is soluble only in high-salt (1 M NaCl) buffer. It is located exclusively within the cotyledons, in association with a cellulosic cell-wall fraction. Its substrates are the products of endosperm cell-wall mobilization, mannobiose and mannotriose, which diffuse to the cotyledons and are hydrolyzed extracellularly by the beta mannoside mannohydrolase. PMID- 24232645 TI - The effect of oxygen on nitrate and nitrite assimilation in leaves of Zea mays L. under dark conditions. AB - The assimilation of nitrate under dark-N2 and dark-O2 conditions in Zea mays leaf tissue was investigated using colourimetric and (15)N techniques for the determination of organic and inorganic nitrogen. Studies using (15)N indicated that nitrate was assimilated under dark conditions. However, the rate of nitrate assimilation in the dark was only 28% of the rate under non-saturating light conditions. No nitrite accumulated under dark aerobiosis, even though nitrate reduction occurred under these conditions. The pattern of nitrite accumulation in leaf tissue in response to dark-N2 conditions consisted of three phases: an initial lag phase, followed by a period of rapid nitrite accumulation and finally a phase during which the rate of nitrite accumulation declined. After a 1-h period of dark-anaerobiosis, both nitrate reduction and nitrite accumulation declined considerably. However, when O2 was supplied, nitrate reduction was stimulated and the accumulated nitrite was rapidly reduced. Anaerobic conditions stimulated nitrate reduction in leaf tissue after a period of dark-aerobic pretreatment. PMID- 24232646 TI - Polypeptide pattern and enzymic character of vacuoles isolated from barley mesophyll protoplasts. AB - Intact chloroplasts and vacuoles were isolated from mesophyll protoplasts of barley. The chloroplasts occupied about 15% of the cellular volume and contained 75% of the protein, whereas the vacuoles occupied about 80% of the volume and contained less than 4% of total cellular protein. Contamination of the vacuolar fraction by foreign protein is included in these values. Chlorophyll was absent from the vacuolar fraction, but less than 1% of several extra-vacuolar marker proteins were still present. The vacuoles contained hydrolytic enzymes. Several of them (alpha-mannosidase, alpha-galactosidase, N-acetylglucosaminidase) were soluble, whereas part of the activity of others semimented with the tonoplasts during centrifugation. Attached proteins could be released from the membranes during freezing in the presence of NaCl. One-dimensional gel electrophoretic separation of soluble vacuolar proteins under non-denaturing conditions yielded more than 10 protein bands. A comparative analysis was performed of thylakoids and vacuoles which were subfractionated into tonoplasts and soluble vacuolar constituents. Sodium dodecyl sulfate gel electrophoresis separated about 15 polypeptides of the soluble fraction which reacted with silver reagent. The tonoplast fraction yielded about 20 bands. A similar number of bands was observed when vacuoles incubated with the (14)C-labelled SH-reagent N-ethylmaleimide were analysed for radioactive polypeptides. Silverstaining of the polypeptides and their SH-content did not correlate. Several polypeptides of the vacuolar fraction had molecular weights very similar to the molecular weights of known chloroplast proteins. However, with the exception of the two subunits of ribulose-1,5 bisphosphate carboxylase, contamination of the vacuolar fraction by chloroplast proteins could be ruled out as a possible cause of the close correspondence. The lipophilic carboxylic-group reagent N,N'-dicyclohexylcarbodiimide ([(14)C]DCCD) reacted with several polypeptides of thylakoids and tonoplasts. However, the labelling patterns were different. The most heavily labelled polypeptide of thylakoids was the 8-kDa polypeptide of the basal part of the coupling factor CF0. Tonoplast polypeptides heavily labelled with [(14)C]DCCD had molecular weights of 24, 28, and 56 kDa. The vacuolar 8-kDa polypeptide remained unlabelled. PMID- 24232647 TI - An efficient method for the determination of K m values for HCO 3 (-) of phosphoenolpyruvate carboxylase. AB - One of the most serious problems in obtaining estimates of the K m values for HCO 3 (-) of phosphoenolpyruvate carboxylase (PEPCase; EC 4.1.1.31) by measurement of initial rates at varying HCO 3 (-) is the impossibility of completely excluding any contaminating HCO 3 (-) . A method is proposed which has no need for the careful control of HCO 3 (-) /CO2 contamination. The kinetic data are obtained by the evaluation of progress curves of HCO 3 (-) consumption. The method is discussed and the K m values for HCO 3 (-) of PEPCase from several C4-species are presented. PMID- 24232648 TI - Effects of nitrogen starvation on the function and organization of the photosynthetic membranes in Cryptomonas maculata (Cryptophyceae). AB - Nitrogen deficiency affects both photosystems and the antennae pigment systems in the photosynthetic apparatus of the marine alga, Cryptomonas maculata. Under increasing energy fluence rates, O2 evolution in nitrogen-deficient (-N) cell suspensions never reached a positive value; in control cultures (+N), O2 evolution increased and was saturated at about 6.4 W.m(-2) with about 100 MUmol O2.mg chlorophyll(-1).h(-1). During fluorescence-induction experiments at room temperature, Fo and Fmax were significantly increased in-N cells whereas the Fvar/Fmax ratio decreased from 0.6 to 0.1. These observations can be correlated with a significantly decreased population of 12.5-nm-size particles in the exoplasmic-fracture (EF) faces of freeze-cleaved thylakoid membranes in-N cells (Rhiel et al., 1985, Protoplasma 129, 62-73). The EF particles are suggested to represent photosystem II associated with chlorophyll a/c-protein complexes (LHCP). The banding pattern of isolated and Triton X-100-solubilized thylakoid membranes of both +N and-N cells in sucrose gradients showed that the LHCP is still present in-N cells. The same applies to sodium dodecyl sulfate polyacrylamide gel electrophoresis of these membrane fractions. The reduced number of the 12.5-nm particles in the EF faces of-N cells may be a result of decoupling of the LHCP constituents of the photosystem-II complex rather than their degradation. This is supported by high values for the initial fluorescence Fo in fluorescence-induction experiments and, in part, is indicated by the shift of the maximal fluorescence emission from 693 nm in +N to 684 nm in-N cells. The lack of the CP1 band in the gels of sodium dodecyl sulfate-solubilized thylakoid membranes from-N cells after electrophoresis demonstrates that photosystem I is also severely affected. PMID- 24232649 TI - Light dependence of sexual agglutinability in Chlamydomonas eugametos. AB - The mating activity of mating-type plus gametes of Chlamydomonas eugametos depends on light. Cells lost their ability to agglutinate with mating-type minus gametes after a dark period of 30 min. They regained their agglutinability after 10 min exposure to light. Other mating reactions, such as tipping and flagellar tip activation, were not dependent upon light. Since cycloheximide and tunicamycin did not affect the light-induced activation of flagellar agglutinability, no protein synthesis or glycosylation is involved in this process. Equal amounts of biologically active agglutination factor could be extracted from cells placed either in light or in darkness. A minor portion of the active material was found to be located on the flagellar surface of illuminated cells. No active material was found on the flagellar surface of dark exposed cells, whereas their cell bodies contained the same amount of active material as the cell bodies of illuminated cells. Since a light-induced flow of agglutination factors from the cell body to the flagella could not be detected and dark-exposed cells could be slightly activated by amputation or fixation by glutaraldehyde, we propose that light affects flagellar agglutinability by an in situ modification of the agglutination factor on the flagella. When mt (+) and mt (-) strains were crossed and the progeny examined for light-sensitivity, it was apparent that this phenomenon is not mating type-linked. PMID- 24232650 TI - Absence of the glutamine-synthetase-linked methylammonium (ammonium)-transport system in the cyanobiont of Cycas-cyanobacterial symbiosis. AB - Using the ammonium analogue (14)CH3NH 3 (+) , ammonium transport was studied in the cyanobiont cells freshly isolated from the root nodules of Cycas revoluta. An L-methionine-DL-sulphoximine (MSX)-insensitive ammonium-transport system, which was dependent on membrane potential (DeltaPsi), was found in the cyanobiont. However, the cyanobiont was incapable of metabolizing exogenous (14)CH3NH 3 (+) or NH 4 (+) because of the absence of another ammonium-transport system responsible for the uptake of ammonium for assimilation via glutamine synthetase (EC 6.3.1.2). Such a modification seems to be the result of symbiosis because the free-living cultured isolate, Anabaena cycadeae, has been shown to possess both the ammonium-transport systems. PMID- 24232651 TI - The role of malate in ammonia assimilation in cotyledons of radish (Raphanus sativus L.). AB - The relationships between the metabolism of malate, nitrogen assimilation and biosynthesis of amino acids in response to different nitrogen sources (nitrate and ammonium) have been examined in cotyledons of radish (Raphanus sativus L.). Measurements of the activities of some key enzymes and pulse-chase experiments with [(14)C]malate indicate the operation of an anaplerotic pathway for malate, which is involved in the synthesis of glutamine during increased ammonia assimilation. It is most likely that the tricarboxylicacid cycle is supplied with carbon through entry of malate, formed via the phosphoenolpyruvate (PEP) carboxylation pathway, when 2-oxoglutarate leaves the cycle to serve as precursor for an increased synthesis of glutamine via glutamate. This might occur predominantly in the cytosol via the activity of the glutamine synthetase/glutamate synthase (GS/GOGAT) cycle, the NADH-dependent GOGAT being the rate-limiting activity. PMID- 24232652 TI - Fluence dependence of the ultraviolet-light-induced accumulation of chalcone synthase mRNA and effects of blue and far-red light in cultured parsley cells. AB - The fluence dependence of the time course of accumulation of chalcone synthase mRNA in ultraviolet (UV)-light-irradiated cell suspension cultures of parsley (Petroselinum crispum) and the additional effects of blue and far-red light have been investigated. Variations of the UV fluence had no detectable influence on the initial rate of increase in mRNA amount or translational activity, nor on the preceding lag period of approximately 3 h, but strongly influenced the duration of the transient increase. The effects were the same whether the fluence rate or the time of irradiation was varied to obtain a given fluence. Blue-light pretreatment of the cells resulted in increased amounts of mRNA and abolished the apparent lag period. This effect remained cryptic without the subsequent UV-light treatment. Irradiation with long-wavelength far-red light following UV-light pulses shortened the duration of the mRNA accumulation period. This effect was not altered by a preceding blue-light treatment. Thus, three photoreceptors, a UV B receptor, a blue-light receptor and phytochrome, participate in the regulation of chalcone synthase mRNA accumulation in this system. PMID- 24232653 TI - Regulation of synthesis of proteinase inhibitors I and II mRNAs in leaves of wounded tomato plants. AB - Levels of two wound-inducible serine proteinase inhibitors, called Inhibitor I and Inhibitor II, and their mRNAs were quantified in leaves of tomato (Lycopersicon escululentum (L.) Mill.) plants after wounding the leaves with a hemostat. A single wound on a lower leaf of 25-old tomato plants caused the accumulation of the two inhibitor proteins in wounded and non-wounded leaves beginning about 4-6 h following wounding. The rate of inhibitor accumulation was maximal in leaves for the next 4 h and then declined. By 20 h the accumulation had nearly ceased. Following a single wound, Inhibitor I mRNA [600 bases in length] and Inhibitor II mRNA (760 bases) began to accumulate in wounded leaves about 2 h before the inhibitor proteins could be detected. The levels of mRNA for both inhibitors reached a maximum at about 8 h following wounding and then decayed, both with apparent half lives of about 10 h. Four consecutive wounds, inflicted hourly, increased the levels of mRNA for both inhibitors to over twice the levels induced by a single wound. Within 4 h following multiple wounds, Inhibitor I mRNA represented about 0.5% of the total polyadenylated mRNA (poly(A(+))mRNA) and Inhibitor II mRNA about 0.15% of the total. The rates of accumulation of the two inhibitor proteins varied depending upon the age of the plants and their environment during growth, and ranged between 3 and 10 MUg Inhibitor I.h(-1).(g tissue)(-1) for Inhibitor I and about half of these rates for Inhibitor II. Nuclei were isolated from leaves of wounded and non-wounded plants, and in mRNA runoff experiments using specific inhibitor copy DNAs (cDNAs) as probes the synthesis of Inhibitor I and II mRNAs were shown to be regulated, at least in part, at the level of transcription. PMID- 24232654 TI - Redistribution of growth during phototropism and nutation in the pea epicotyl. AB - First positive phototropism of the third internode of intact, 5-d-old pea (Pisum sativum L.) seedlings, grown under continuous, dim red light, showed maximal response following a photon fluence of 3 MUmol.m(-2) blue light. Greater or lesser fluences (with irradiation time 100 s or less) caused less bending, no response being detectable above 300 or below 0.03 MUmol.m(-2). Bilateral irradiation with blue light caused no detectable inhibition of growth rate over that range of fluences. The linear nutation of the pea third internode was shown to be driven by a balanced oscillation of growth rate such that the overall growth rate was little changed during the oscillation. Phototropic stimulation changed neither the amplitude nor the period of nutation. Nutation and phototropism probably regulate growth independently. Phototropism in response to the optimal blue light fluence was caused by concomitant depressed growth on the irradiated side and stimulated growth on the shaded side of the bending internode. These results are consistent with the Cholodny-Went hypothesis which states that unilateral blue light induces a lateral redistribution of a growth regulator. PMID- 24232655 TI - Purification and characterization of barley-aleurone xylanase. AB - Xylanase (beta-1,4-D-xylan xylanohydrolase; EC 3.2.1.8) from aleurone layers of barley (Hordeum vulgare L. cv. Himalaya) was purified and characterized. Purification was by preparative isoelectric focusing and a Sephadex G-200 column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme showed a single protein band with an apparent molecular weight (Mr)=34000 daltons. The isoelectric point of the enzyme was 4.6. The enzyme had maximum activity on xylan at pH 5.5 and at 35 degrees C. It was most stable between pH 5 and 6 and at temperatures between 0 and 4 degrees C. The Km was 0.86 mg xylan.ml(-1). PMID- 24232656 TI - Expression of alpha-amylase and other gibberellin-regulated genes in aleurone tissue of developing wheat grains. AB - Aleurone tissue from freshly harvested immature wheat grains (Triticum aestivum L. cv. Sappo) which is normally unresponsive to gibberellic acid can be made responsive by subjecting the tissue to a pre-incubation treatment in a simple buffered medium prior to the addition of the growth substance. The effectiveness of this treatment is dependent on grain age, with grains less than 15-20 days post anthesis failing to become converted to a responsive state whilst tissue from grains older than this become increasingly susceptible. Tissue from grains of a certain age (approx. 25-28 days post anthesis) produce small amounts of alpha-amylase following this treatment even in the absence of exogenously applied growth substance. Using different (32)-labelled complementary-DNA probes for alpha-amylase in wheat it was demonstrated that the failure of freshly harvested tissue to produce alpha-amylase was correlated with the absence of the appropriate mRNA species. Inability to accumulate alpha-amylase mRNA in response to gibberellic acid was removed by the pre-iccubation treatment and also by enforced drying. The gibberellin-regulated expression of other unidentified genes also responds to pre-incubation or drying. Induction of gibberellin responsiveness in immature aleurone cells did not extend to the secretion of acid phosphatase, protease and ribonuclease. PMID- 24232657 TI - Adaptation of photosynthetic electron-transport rate to growth temperature in pea. AB - Pea (Pisum sativum L. cv. Feltham First) plants were germinated and grown under two temperature regimes, one chilling (6-8 degrees C) and one non-chilling (16 18 degrees C), which are referred to as "cold-grown" and "warm-grown", respectively. It was found that: (1) At saturating light intensity and with excess CO2, cold-grown leaves exhibited faster rates of oxygen evolution than warm-grown leaves when measured below 15 degrees C. However when measurements were carried out above this temperature, the reverse relationship was observed. (2) Full-chain electron-transport measurements on thylakoids showed that those isolated from cold-grown plants had greater light-saturated uncoupled rates than their warm-grown equivalents at all temperatures between 3 and 19 degrees C. (3) This difference was apparently not due to a greater activity of photosystem I or II in the thylakoids from cold-grown plants, but rather to a more rapid turnover of a dark step within the electron-transport chain. These results are interpreted in terms of a previously reported apparent homeoviscous adaptation of the pea thylakoid membrane to growth temperature (J. Barber, R.C. Ford, R.A.C. Mitchell, P.A. Millner, 1984, Planta 161, 375-380). PMID- 24232658 TI - In-vivo measurement of cell-wall extensibility in maize coleoptiles: Effects of auxin and abscisic acid. AB - Plastic and elastic in-vivo extensibilities (Epl and Eel, respectively) of cell walls of growing maize (Zea mays L.) coleoptile segments were measured by stretching living tissue at constant force (creep test) in an extensiometer. The linear displacement transducer used as a measuring device permits the determination of load-induced extensions in the range of 0-1% of the segment's length, leading to a minimal disturbance of the hydraulic parameters of the tissue and allowing the measurement of unidirectional cell-wall creep at virtually unchanged turgor and metabolic activity. A rein-vestigation of the time course of indole-3-acetic acid-promoted and abscisic acid-inhibited wall loo sening revealed that the in-vivo creep test yields results very similar to those obtained previously with the in-vitro creep test [Kutschera and Schopfer, 1986, Planta 167, 527-535]. The hormones affect elongation rate and Epl in a closely correlated manner both in step-up as well as step-down growth changes whereas Eel remains unaltered. It is argued that both hormones influence growth by modifying Epl of the outer epidermis and that this effect can be quantitatively measured, in relative units, by either the in-vivo or the in-vitro creep test. PMID- 24232659 TI - In-vivo formation of xyloglucan nonasaccharide: A possible biologically active cell-wall fragment. AB - The in-vivo formation of a specific nonasaccharide of xyloglucan was investigated. This nonasaccharide has been reported to have biological activity, inhibiting auxin-induced growth in pea stem segments. Cell-suspension cultures of spinach were grown in the presence of [(3)H]arabinose and [(3)H]fucose, and the culture-filtrates were examined for oligosaccharides by gelpermeation chromatography and by paper chromatography. Sixteen [(3)H]pentose-containing oligosaccharides were found, including twelve that contained the sequence [(3)H]xylosyl-alpha(1->6)-glucose, which is diagnostic of xyloglucan. In addition, [(3)H]fucose-containing oligosaccharides of at least three sizes were found. Radiochemical evidence is presented that one of these oligosaccharides was labelled with both [(3)H]fucose and with [(3)H]pentose, and was identical with the major xyloglucan-derived nonasaccharide associated with anti-auxin activity. It was largely present in the form of acylated (possibly acetylated) derivatives. It accumulated extracellularly to a steady-state concentration of about 4.3.10( 7)M. This is the first report of the production of a biologically-active oligosaccharide by living plant cells. PMID- 24232660 TI - Neoplastic progression in crown gall in tobacco without elevated auxin levels. AB - We have isolated two stable variants from a crown-gall teratoma tissue of tobacco (Nicotiana tabacum L.) transformed by Agrobacterium tumefaciens strain A66, a mutant of the virulent A6 strain containing an insertion sequence in the tumor inducing (Ti) plasmid at the locus coding for auxin biosynthesis. Normally tobacco cells transformed by strain A66 spontaneously form shoots in culture and will not grow on hormone-free medium unless shoots develop. The variant tissue lines, isolated from the teratoma tissue after prolonged culture in the dark, grew as friable and unorganized tissues on hormone-free growth medium. Growth of the variants was more sensitive to auxin feeding than growth of the parental teratoma line, and the auxin dose-response curves of the variant lines were similar to those obtained with A6-transformed tobacco cells. Southern blot analysis of DNA from the parental teratoma line and one of the variants showed no differences in copy number or organization of the oncogenic DNA sequence (T-DNA) transferred from the bacterium, indicating that the variant phenotype did not result from reversion of the A66 mutation. Radio-immunoassay analysis showed similar levels of indole-3-acetic acid (IAA) in the variants and parental teratoma line (3-50 and 38-42 pmol.(gFW)(-1), respectively), whereas an A6 transformed cell line contained much higher IAA levels (150-1200 pmol.(g FW)( 1)). Low levels of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid in the variants and the parental teratoma line (<5 nmol.(g FW)(-1)) as compared with that found in the A6-transformed line (>100 nmol. (g FW)(-1)) provided additional, indirect evidence for low auxin levels in the variant lines. These results indicate that crown-gall teratoma tissues of tobacco may switch to the unorganized, auxin-sensitive phenotype without an increase in auxin content. PMID- 24232661 TI - Cytokinin effect on branching and bud formation in Funaria. AB - Cytokinins have two different effects on protonemata of Funaria hygrometrica. They induce branching of unbranched caulonemata and bud formation. Branching occurs after treatment with pico-molar concentrations of cytokinins whereas bud formation requires micro-molar concentrations. Both processes are therefore independently stimulated by cytokinins. PMID- 24232662 TI - Erratum. PMID- 24232663 TI - Predicted organic compounds derived from rare gas atoms and formic acid. AB - Organic insertion compounds of rare gas atoms into formic acid were investigated at the MP2(full)/aug-cc-pVTZ level. There are two configuration isomers for each molecule based on the location of H atoms: trans- and cis-HCOORgH (Rg = Ar, Kr, Xe). Their structures, harmonic frequencies, and decomposition energies have been calculated using the above ab initio method. Using trans-HCOOXeH as an example, natural bond orbital (NBO) and atom-in-molecules (AIM) analyses were also carried out to explore the binding nature of the rare gas atoms. The formation mechanism of molecular orbitals is also presented in this paper. The presented results indicate that HCOOXeH and HCOOKrH are potential candidates for experimental observation. PMID- 24232664 TI - IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes. AB - OBJECTIVE: To evaluate the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria versus the American Diabetes Association (ADA) criteria for diagnosing gestational diabetes mellitus (GDM) in China. STUDY DESIGN: Overall, 3083 women with a singleton pregnancy underwent a 75-g, 2-h oral glucose tolerance test between 24 and 28 weeks of pregnancy, and both IADPSG and ADA criteria were used for GDM diagnosis. Adverse pregnancy outcomes (APOs), including preterm birth, required Cesarean section, preeclampsia, macrosomia and low birth weight, were recorded and analyzed. RESULT: IADPSG and ADA criteria diagnosed 19.9% and 7.98% of women with GDM, respectively (P<0.001). IADPSG criteria has a stronger capacity of predicting APOs than ADA criteria (odds ratio (OR)=1.84, 95% confidence interval (CI): 1.52-2.25 for IADPSG, and OR=1.54, 95% CI: 1.16-2.05 for ADA). CONCLUSION: IADPSG criteria increase GDM diagnosis by almost twofold. GDM diagnosed by IADPSG criteria is more associated with APOs, although the economic impact needs further evaluation. PMID- 24232665 TI - Bach music in preterm infants: no 'Mozart effect' on resting energy expenditure. AB - OBJECTIVE: To study whether Johan Sebastian Bach music has a lowering effect on resting energy expenditure (REE) similar to that of Wolfgang Amadeus Mozart music. STUDY DESIGN: Prospective, randomized clinical trial with cross-over in 12 healthy, appropriate weights for gestational age (GA), gavage fed, metabolically stable, preterm infants. Infants were randomized to a 30-min period of either Mozart or Bach music or no music over 3 consecutive days. REE was measured every minute by indirect calorimetry. RESULT: Three REE measurements were performed in each of 12 infants at age 20+/-15.8 days. Mean GA was 30.17+/-2.44 weeks and mean birthweight was 1246+/-239 g. REE was similar during the first 10-min of all three randomization periods. During the next 10-min period, infants exposed to music by Mozart had a trend toward lower REE than when not exposed to music. This trend became significant during the third 10-min period. In contrast, music by Bach or no music did not affect significantly REE during the whole study. On average, the effect size of Mozart music upon REE was a reduction of 7.7% from baseline. CONCLUSION: Mozart music significantly lowers REE in preterm infants, whereas Bach music has no similar effect. We speculate that 'Mozart effect' must be taken into account when incorporating music in the therapy of preterm infants, as not all types of music may have similar effects upon REE and growth. PMID- 24232666 TI - UGT1A1 gene variants and clinical risk factors modulate hyperbilirubinemia risk in newborns. AB - OBJECTIVE: To study the contribution of UGT1A1 gene variants and clinical risk factors in modulating hyperbilirubinemia risk in newborns. STUDY DESIGN: Seven UGT1A1 gene variants and clinical risk factors were studied in 113 hyperbilirubinemia cases and 218 control newborns. Hyperbilirubinemia was defined as the total serum bilirubin levels >95th percentile of the American Academy of Pediatrics nomogram. The study population included term (37 to 41 weeks) newborns below 2 weeks of age. RESULT: UGT1A1 gene variants, namely, c.211G>A, g.-3279T>G, TATA box polymorphism and CAT insertion were identified as independent molecular risk factors for neonatal hyperbilirubinemia, whereas c.686C>A, c.1091C>T and c.1456T>G were not detected in study cohort. Among clinical risk factors, excessive weight loss, sepsis and ABO incompatibility emerged as independent risk factors. Co-expression of UGT1A1 variants and clinical risk factors further accentuated the risk of neonatal hyperbilirubinemia. CONCLUSION: Multiple risk factors, whether genetic or clinical, are instrumental in modulating hyperbilirubinemia risk in newborns. Disordered bilirubin conjugation through interactions of UG1TA1 gene variants contributes to the clinical phenotype of neonatal hyperbilirubinemia. PMID- 24232667 TI - Design and synthesis of pro-apoptotic compounds inspired by diatom oxylipins. AB - Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play a role in the reproductive failure of copepod predators, showing clear pro-apoptotic effects on newborn nauplii. In this work, these compounds were tested for the ability to induce mitotic arrest in sea urchin embryos. We show for the first time that oxylipins have an increased efficacy in their corresponding methylated form. Natural oxylipins were also used as an inspiration for the rational design and synthesis of stable chemical analogs with apoptotic activity against tumor cell lines. This approach led to the synthesis of the linear C15-ketol (22) that was shown to induce apoptosis in human leukemia U-937 cells. These results are proof of the concept of the use of eco-physiological considerations as a platform to guide the search for novel drug candidates. PMID- 24232668 TI - Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus. AB - New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo gamma-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, gamma-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID- 24232669 TI - Improvement of neutral lipid and polyunsaturated fatty acid biosynthesis by overexpressing a type 2 diacylglycerol acyltransferase in marine diatom Phaeodactylum tricornutum. AB - Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral as structural and functional components of cellular membranes, as well as precursors of various lipid mediators. In addition, diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the last step of triacylglyceride (TAG) biosynthesis. However, a comprehensive sequence-structure and functional analysis of DGAT in diatoms is lacking. In this study, an isoform of diacylglycerol acyltransferase type 2 of the marine diatom Phaeodactylum tricornutum was characterized. Surprisingly, DGAT2 overexpression in P. tricornutum stimulated more oil bodies, and the neutral lipid content increased by 35%. The fatty acid composition showed a significant increase in the proportion of polyunsaturated fatty acids; in particular, EPA was increased by 76.2%. Moreover, the growth rate of transgenic microalgae remained similar, thereby maintaining a high biomass. Our results suggest that increased DGAT2 expression could alter fatty acid profile in the diatom, and the results thus represent a valuable strategy for polyunsaturated fatty acid production by genetic manipulation. PMID- 24232670 TI - New aQTL SNPs for the CYP2D6 identified by a novel mediation analysis of genome wide SNP arrays, gene expression arrays, and CYP2D6 activity. AB - BACKGROUND: The genome-wide association studies (GWAS) have been successful during the last few years. A key challenge is that the interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data into GWAS may provide clues elucidating the mechanisms by which a genetic variant leads to a disease. METHODS: Here, we developed a novel mediation analysis approach to identify new expression quantitative trait loci (eQTL) driving CYP2D6 activity by combining genotype, gene expression, and enzyme activity data. RESULTS: 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are found strongly associated (P < 10-5, FDR = 16.6% and 11.7%) for two different genotype platforms, namely, Affymetrix and Illumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes in the expression of distant genes by affecting major regulators or transcription factors (TFs), which would be visible as an eQTL hotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery of 64 TFs. CONCLUSIONS: Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It improves our understanding of the functional genetic variations for the liver metabolism mechanisms. PMID- 24232671 TI - Effect of hemodialysis on intraocular pressure and ocular perfusion pressure. AB - IMPORTANCE: Elevated intraocular pressure (IOP) and decreased ocular perfusion pressure (OPP) are risk factors for glaucoma development and progression. Unrecognized significant IOP elevation or OPP reduction during hemodialysis (HD) could lead to glaucomatous optic nerve damage and subsequent visual loss. OBJECTIVE: To evaluate changes in IOP and OPP during HD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional observational study was conducted in patients undergoing HD at an ambulatory care clinic at the University of Illinois at Chicago. EXPOSURES: Forty-nine patients (97 eyes) undergoing HD were enrolled. Exclusion criteria included preexisting corneal abnormalities, history of corneal surgery, allergy to topical anesthetic agents, and current eye infection. Nine patients had previous diagnoses of open-angle glaucoma (OAG) or suspected glaucoma. At 3 time points, IOP was measured using a pneumatonometer and blood pressure was recorded. Measurements were made with the patient in a seated position approximately 15 minutes before starting HD (T1), approximately 2 hours after starting HD (T2), and approximately 15 minutes after ending HD (T3). Mean arterial pressure (MAP) and OPP (systolic, diastolic, and mean OPP) were calculated. MAIN OUTCOMES AND MEASURES: Intraocular pressure and OPP. RESULTS: From T1 to T3, IOP significantly increased by 3.1 mm Hg (both eyes, P < .001), MAP significantly decreased by 5.8 mm Hg (P = .05), and all OPP measures significantly decreased from baseline (all P <= .02). Using previously reported thresholds of increased glaucoma development and progression risk, 53% of the right eyes (26 of 49) and 46% of the left eyes (22 of 48) had a systolic OPP of 101 mm Hg or less, 71% of the right eyes (35 of 49) and 73% of the left eyes (35 of 48) had a diastolic OPP of 55 mm Hg or less, and 63% of the right eyes (31 of 49) and 65% of the left eyes (31 of 48) had a mean OPP of 42 mm Hg or less. CONCLUSIONS AND RELEVANCE: Significantly increased IOP and decreased OPP occur during HD, bringing both to levels that increase the risk of glaucoma development and progression. Clinicians should consider HD history in patients who have glaucoma progression, even when IOP has been well controlled. Such patients may benefit from IOP and blood pressure monitoring during HD sessions to minimize OPP changes resulting from IOP spikes and/or suboptimal blood pressure. PMID- 24232673 TI - Effect of auxin on cytodifferentiation and production of quinoline alkaloids in compact globular structures of Cinchona ledgeriana. AB - Fine cell suspension cultures of Cinchona ledgeriana produce only very low amounts of quinoline alkaloids. These cultures formed self-propagating compact globular structures (CGS) on medium containing 2,4-D and BAP. These CGS could be induced to produce significant amounts of quinoline alkaloids by replacing 2,4-D by low amounts of 1-NAA, which was accompanied by histological changes of the CGS. A few high producing CGS clones could be selected. The stability of this trait was studied over a period of about one year of culture in maintenance medium. PMID- 24232672 TI - Neuroendoscopic surgery versus external ventricular drainage alone or with intraventricular fibrinolysis for intraventricular hemorrhage secondary to spontaneous supratentorial hemorrhage: a systematic review and meta-analysis. AB - BACKGROUND AND PURPOSE: Although neuroendoscopy (NE) has been applied to many cerebral diseases, the effect of NE for intraventricular hemorrhage (IVH) secondary to spontaneous supratentorial hemorrhage remains controversial. The purpose of this study was to analyze the effect of NE compared with external ventricular drainage (EVD) alone or with intraventricular fibrinolysis (IVF) on the management of IVH secondary to spontaneous supratentorial hemorrhage. METHODOLOGY/ PRINCIPAL FINDINGS: A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science, The Cochrane Library, CBM, VIP, CNKI, and Wan Fang database) was performed to identify related studies published from 1970 to 2013. Randomized controlled trials (RCTs) or observational studies (OS) comparing NE with EVD alone or with IVF for the treatment of IVH were included. The quality of the included trials was assessed by Jaded scale and the Newcastle Ottawa Scale (NOS). RevMan 5.1 software was used to conduct the meta-analysis. RESULTS: Eleven trials (5 RCTs and 6 ORs) involving 680 patients were included. The odds ratio (OR) showed a statistically significant difference between the NE + EVD and EVD + IVF groups in terms of mortality (OR, 0.31; 95% CI, 0.16-0.59; P=0.0004), effective hematoma evacuation rate (OR, 25.50, 95%CI; 14.30, 45.45; P<0.00001), good functional outcome (GFO) (OR, 4.51; (95%CI, 2.81-7.72; P<0.00001), and the ventriculo-peritoneal (VP) shunt dependence rate (OR, 0.16; 95%CI; 0.06, 0.40; P<0.0001). CONCLUSION: Applying neuroendoscopic approach with EVD may be a better management for IVH secondary to spontaneous supratentorial hemorrhage than NE + IVF. However, there is still no conclusive evidence regarding the preference of NE vs. EVD alone in the case of IVH, because insufficient data has been published thus far. This study suggests that the NE approach with EVD could become an alternative to EVD + IVF for IVH in the future. PMID- 24232674 TI - Photosynthetic ability in dark-grown Reboulia hemisphaerica and Barbula unguiculata cells in suspension culture. AB - Suspension cultured cells of the liverwort, Reboulia hemisphaerica and of the moss, Barbula unguiculata were independently subcultured in the medium containing 2% glucose in the dark or in the light for more than one year, and the photosynthetic activities of the final cultures were determined. Throughout the culture period light-grown cells of both species contained high amount of chlorophyll (4 to 34 MUg mg(-1) dry weight) and showed a high photosynthetic activity (10 to 84 MUmol O2 mg(-1) chlorophyll h(-1)). Dark-grown cells of R. hemisphaerica showed the same level of chlorophyll content and photosynthetic O2 evolving activity as light-grown cells. Although chlorophyll content in dark grown B. unguiculata cells was ten-fold lower than that in light-grown cells, the photosynthetic activity of these dark-grown cells was higher than that of light grown cells based on chlorophyll content. PMID- 24232675 TI - Induction of freezing tolerance in microspore-derived embryos of winter Brassica napus. AB - Freezing tolerance was induced in microspore derived embryos of winter Brassica napus cv. Jet neuf by the addition of ABA or mefluidide to the culture media during embryogenesis. Survival after freezing was estimated by culture of frozen thawed embryos to plantlets. A higher freezing tolerance (50% survival at -15 degrees C) was induced when 50 MUM ABA or 3.2 MUM mefluidide was incorporated initially into the medium during embryogenesis at 25 degrees C followed by culture at 2 degrees C for 3 weeks. When embryos were induced in the absence of ABA or mefluidide and maintained at 2 degrees C for even as long as 12 weeks a lower degree of freezing tolerance (10% survival at -15 degrees C) was obtained. Plants regenerated from embryos hardened maximally by a combination of either ABA or MFD with low temperature did not require further vernalization for flowering. PMID- 24232676 TI - Protoplast production in Chondrus crispus gametophytes (gigartinales, rhodophyta). AB - Protoplasts were isolated from female gametophytes of Chondrus crispus (Stackh.) using commercial cellulase and various carrageenases prepared from marine bacteria. Depending on the nature of the donor tissue (apices or whole thallus, wild or cultivated strains), yields ranged from 1.0-8.5*10(8) protoplasts per gram of fresh tissue. Preincubating the tissue with a potassium chelator, Kryptofix 222, enhanced protoplast yields by 30-50 %. Based on staining with fluorescein diacetate most protoplasts were viable. A few protoplasts regenerated a cell wall and divided. PMID- 24232677 TI - Transformation of cotton (Gossypium hirsutum L.) via particle bombardment. AB - Embryogenic suspension cultures of cotton (Gossypium hirsutum L.) were subjected to particle bombardment, where high density particles carrying plasmid DNA were accelerated towards the embryogenic plant cells. The plasmid DNA coating the particles encoded hygromycin resistance. One to two weeks following bombardment, embryogenic cotton cells were placed in proliferation medium containing 100 MUg/ml hygromycin. Clumps of tissue which grew in the presence of hygromycin were subcultured at low density into fresh hygromycin-containing proliferation medium. Following sequential transfer of embryogenic tissue to development and then germination media, plants were recovered from transgenic embryogenic tissue. Southern hybridization confirmed the presence of the hygromycin resistance gene in embryogenic suspension culture tissue and regenerated plants. PMID- 24232678 TI - Oat mesophyll protoplasts: their response to various feeder cultures. AB - Oat (Avena sativa L.) mesophyll protoplasts were recently demonstrated to be capable of dedifferentiation, repeated divisions, and colony formation. Since the development of oat mesophyll protoplasts is decisively influenced by the nature of the used feeder culture (species, variety and concentration), we conducted a systematic study of this parameter. Generally, graminaceous feeders promoted protoplast proliferation, while dicot species repressed protoplast divisions. The beneficial effect of those feeders that promote divisions was counterbalanced by a factor that causes necrosis. The correct balance between promotion of divisions or necrosis depended on the nature of the feeder and its plating density. PMID- 24232679 TI - Effects of culture density, conditioned medium and feeder cultures on microspore embryogenesis in Brassica napus L. cv. Topas. AB - In microspore cultures of Brassica napus L. cv. Topas, embryo yield increases with culture density up to about 40,000 microspores per ml. A much higher density (100,000 per ml) appears inhibitory to embryogenesis. A relatively high culture density (30,000 or 40,000 per ml) for the first 2-4 days of culture is crucial for embryogenesis, after which cultures may be diluted to allow better embryo growth.Medium conditioned by culturing microspores at 30,000 or 40,000 per ml for 1 day improved microspore-embryo yield in low density cultures (3,000 or 4,000 per ml) more than 3-fold. In contrast, media conditioned with microspores from 1 4 days or 0-4 days of culture were inhibitory.Use of feeder cultures resulted in up to 10-fold increase of embryo yield in low density microspore cultures, depending on the method used. Filter papers and other membranes placed on top of feeders greatly inhibited embryogenesis in the feeder layer as well as microspores cultured on the feeder, possibly due to poorer gaseous exchange. PMID- 24232680 TI - Role of inhibitors in the induction of differentiation in callus cultures of Brassica, Datura and Nicotiana. AB - The effect of various inhibitors on differentiation (shoot morphogenesis) in callus cultures of Brassica, Datura and Nicotiana has been investigated. Hormone medium without any inhibitor (control), resulted in 6% shoot formation. Addition of inhibitors such as actinomycin D, cordycepin, abscisic acid, trigonelline and theophylline greatly enhanced shoot formation. The results suggest that inhibitors play a regulatory role in the control of differentiation. PMID- 24232681 TI - Production of terpenes by differentiated shoot cultures of Mentha citrata transformed with Agrobacterium tumefaciens T37. AB - Crown gall initiation on Mentha * piperita var. citrata (Ehrh.) Briq. (mint) was investigated using a range of wild type and mutant strains of Agrobacterium tumefaciens. Axenic transformed shoot cultures of Mentha 'citrata' were established on plant stems inoculated with the nopaline strain T37 of Agrobacterium tumefaciens. The presence of T-DNA in the transformed tissues and the absence of bacterial contamination was established by Southern Blot hybridisation, using (32)P labelled fragments of the T-DNA and virulence region of the Ti plasmid as probes. The shoot cultures synthesised a mint oil fraction which contained the major terpenes characteristic of the parent plant in quantities similar to those found in intact tissue. Oil glands were observed to be present on the leaves of the transformed culture using scanning electron microscopy. PMID- 24232682 TI - Embryogenic and non-embryogenic cell lines of Daucus carota cloned from meristematic cell clusters: relation with cell ploidy determined by flow cytometry. AB - The presence of totipotent and non-totipotent cells in embryogenic carrot cell suspension cultures was examined by cloning of cell microclusters. Forty clones were isolated and the distribution of their embryogenic potential was studied. Nonembryogenic, weakly and highly embryogenic cell lines were selected. After one year of subculture a second cloning round showed that the highly embryogenic and the non-embryogenic cell lines were homogenous and stable. A measurement of ploidy levels of clones by flow cytometry showed that the embryogenic clones were all diploid whereas the non-embryogenic were diploid or tetraploid. Hence, for our strain, there was a strict relationship between the tetraploid state and the inability to produce somatic embryos. PMID- 24232683 TI - In vitro propagation of shoot buds of Carica papaya L. (caricaceae) var. Honey Dew. AB - Shoot buds from the saplings and the fruit bearing plants of Carica papaya L.. var. Honey Dew (papaya) initially treated with Gentamycin were cultured in modified MS media, each with a different hormonal combination, for the establishment of cultures and multiplication and rooting of plants. About 43% of explants from fruit bearing plants and 69% of those from saplings remained free of contamination and retained regeneration capacity when treated in 500 mg/l Gentamycin. For the establishment of the explants a medium containing 1 mg/l GA3 and 2 mg/l kinetin was necessary. When established buds were transferred to medium containing 1 mg/l NAA and 3 mg/l kinetin, calli were initiated at cut ends of shoot buds; multiplication started on transfer to NAA (0.1 mg/l) and BAP (0.5 mg/l) medium. Cultures have been maintained for the last twenty months without any loss in multiplication rate. Rooting was induced in medium with reduced salt concentration containing 2 mg/l IBA. Shoot elongation was induced after prolonged culture in the same rooting medium. PMID- 24232684 TI - Purification of acetyl-CoA: 17-O-deacetylvindoline 17-O-acetyltransferase from Catharanthus roseus leaves. AB - The enzyme acetyl-CoA: 17-O-deacetylvindoline 17-O-acetyltransferase which terminates vindoline biosynthesis has been isolated from Catharanthus roseus leaves, further characterized and purified to homogeneity by three step column chromatography and subsequent preparative isoelectric focusing. Kinetic properties concerning the enzyme reaction are discussed. Five multiple forms of the acetyl-transferase could be observed, each consisting of two subunits. This enzyme is now the best characterized of the enzymes involved in vindoline biosynthesis. PMID- 24232685 TI - Increased capsaicin content in PFP-resistant cells of chili pepper (Capsicum annuum L.). AB - Cell suspensions of chili pepper (Capsicum annuum L.) were subjected to a selection process on semisolid medium containing the amino acid analog p fluorophenylalanine (PFP). Four cell lines with different degrees of resistance were selected and suspension cultures were established from each of them. Resistance was retained even after 75 days of culture in the absence of PFP. PFP resistant cell lines accumu lated higher levels of capsaicin than sensitive lines even after prolonged culture in PFP-free medium. Capsaicin production in non selected cells was only 26.8% of that found in one cell line resistant to 500 MUM PFP. The capsaicin content in the non-selected cell suspension and in one of the resis tant cell lines was 6.7% and 24.9% respectively, that of fruits. PMID- 24232686 TI - Delta5-3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-ketosteroid isomerase (3beta-HSD), a possible enzyme of cardiac glycoside biosynthesis, in cell cultures and plants of Digitalis lanata EHRH. AB - The in vitro transformation of pregnenolone into progesterone in Digitalis lanata tissues was shown to be catalyzed by a 3beta-hydroxysteroid dehydrogenase/ketosteroid isomerase (3beta-HSD). Product formation was monitored by HPLC. The enzyme could be partially characterized and 3beta-HSD activities were measured in various Digitalis lanata tissues and in cell cultures of other plant species. Since no correlation was observed between biosynthetic competence of the tissue and 3beta-HSD activity, it was concluded that this enzyme does not play a major role in regulating cardenolide biosynthesis. PMID- 24232687 TI - Regeneration of plants from achenes and petals of Chrysanthemum coccineum. AB - Achenes and petals of Chrysanthemum coccineum were cultured on MS and White medium supplemented with BA and NAA or 2,4-D. Without being transferred, shoots were formed directly and immediately after callus formation on the surface of the achene walls and from the cut ends of the petals. High concentracions of BA and NAA supported the callus induction and shoot formation, but higher concentrations of 2,4-D inhibited shoot formation. The shoots obtained from both explants formed roots when transferred to hormone-free medium and they could be transplanted to soil for further growth. The regenerated plants contained as much pyrethrins as the original plants. PMID- 24232688 TI - Isolated microspore culture of maize: effects of isolation technique, reduced temperature, and sucrose level. AB - Improvements in ab initio microspore culture of maize are presented using a modified isolation technique, reduced temperature during early stages of culture, and an elevated sucrose level in the culture medium. Blending-isolation, using excised anthers, was less stressful on microspores than pressing anthers against a stainless steel sieve and resulted in a 3-fold increase in the yield of embryo like structures (ELS). Exposure to reduced temperature (15 degrees C) during the first 4 days of culture improved microspore viability and increased by 2-fold the number of ELS produced. Higher levels of sucrose (8.0-9.5%) also resulted in improved response. Maximum yield in the present study was 92 ELS per 100 anther equivalents, exceeding previously reported values of 15 ELS per 100 anther equivalents for ab initio microspore culture of maize. The increase in the total number ELS produced had no observable effect on their quality as evidenced by the frequency of formation of callus capable of regenerating plants. PMID- 24232689 TI - A new technique for the culture of fern gametophytes. AB - Fern gametophytes initiated from spores grew successfully when immobilised in reticulate polyurethane foam in liquid shake cultures. Colonisation of this matrix was complete seven days after medium inoculation and appeared to be a completely passive process. Yield (dry weight) was greater than that from liquid grown cultures. PMID- 24232690 TI - Extramedullary plasmacytoma of median and sural nerve. PMID- 24232691 TI - Importance of family/social support and impact on adherence to diabetic therapy. AB - Diabetes mellitus affects 24 million individuals in the US. In order to manage their diabetes successfully, patients must adhere to treatment regimens that include dietary restrictions, physical activity goals, and self-monitoring of glucose levels. Numerous factors affect patients' ability to adhere properly, eg, self-efficacy, treatment expectations, health beliefs, and lack of social support. Consequently, diabetes management can be quite complex, requiring lifelong commitment and drastic changes to the patient's lifestyle. Empirical studies have shown positive and significant relationships between social support and treatment adherence among patients with diabetes. Social support from family provides patients with practical help and can buffer the stresses of living with illness. However, the exact mechanism by which social support affects patient adherence is not yet completely understood. Further research is needed to address how the differences in types of support, such as functional or emotional support, are linked to outcomes for patients. The purpose of this review is to summarize what is known of the impact of social and family support on treatment adherence in patients with diabetes and to explore the current methods and interventions used to facilitate family support for diabetic patients. PMID- 24232692 TI - Enhancement of non-invasive recording of electroenterogram by means of a flexible array of concentric ring electrodes. AB - Monitoring intestinal myoelectrical activity by electroenterogram (EEnG) would be of great clinical interest for diagnosing gastrointestinal pathologies and disorders. However, surface EEnG recordings are of very low amplitude and can be severely affected by baseline drifts and respiratory and electrocardiographic (ECG) interference. In this work, a flexible array of concentric ring electrodes was developed and tested to determine whether it can provide surface EEnG signals of better quality than bipolar recordings from conventional disc electrodes. With this aim, sixteen healthy subjects in a fasting state (>8 h) underwent recording. The capability of detecting intestinal pacemaker activity (slow wave) and the influence of physiological interferences were studied. The signals obtained from the concentric ring electrodes proved to be more robust to ECG and respiratory interference than those from conventional disc electrodes. The results also show that intestinal EEnG components such as the slow wave can be more easily identified by the proposed system based on a flexible array of concentric ring electrodes. The developed active electrode array could be a very valuable tool for non-invasive diagnosis of disease states such as ischemia and motility disorders of the small bowel which are known to alter the normal enteric slow wave activity. PMID- 24232693 TI - Discovery of retinal elastin and its possible role in age-related macular degeneration. AB - Age-related macular degeneration (AMD) etiology is unknown, but its association to atherosclerotic vascular disease (ASVD) has been observed. Since elastin plays an important role in the atherosclerotic process, to understand ASVD and AMD's relationship we examined retinal elastin existence, elastin amount and vessel properties among normal subjects, mild AMD patients, moderate-to severe AMD patients, and ASVD patients (n = 20). One eye per donor was assigned to enzyme linked immunosorbent assay for quantifying the retinal elastin amount. The rest were assigned to mechanical test for examining the retinal vessel properties. Additionally, two normal human and two porcine eyes were acquired in immunohistochemistry for locating the retinal elastin. We found that elastin presented in the human and porcine retinal vessels at the basement membranes. 3.73 +/- 0.55% of the normal retinal tissues were elastin. Elastin decrease, tissue-weight increase, and vessel hardening and in elasticity (p<0.05) were observed in the retina of patients with ASVD and only moderate-to-severe (i.e., not mild) AMD. Most moderate-to-severe AMD patients also happened to have ASVD. The results suggest that ASVD is unlikely the cause of AMD, but it is perhaps a factor that aggravates the condition through mechanism associated with retinal vessel abnormality. PMID- 24232694 TI - Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives. AB - Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives. PMID- 24232695 TI - A rare synovial sarcoma of the spine in the thoracic vertebral body. AB - INTRODUCTION: Synovial sarcomas of the spine are very rare, most rare of which was occurring in the thoracic vertebral body. The diagnosis of synovial sarcomas was very difficult. It depends on the radiological examination, immunohistochemical examination and gene examination. The best treatment to them was completely surgical resection with negative margins. Other treatments such as radiation therapy and chemotherapy were just adjuvant. The prognosis of synovial sarcomas was disappointing. CASE PRESENTATION: A 26-year-old male patient had low back pain. The radiological examination showed bony erosion of the T7 vertebral body and no soft tissue mass around the spine. He underwent T7 resection en bloc and internal fixation with two levels above T7 and two levels below T7. Then histopathological and gene examination revealed high malignant synovial sarcoma. So he was treated by chemotherapy and external beam radiation therapy after surgery. CONCLUSION: Primary vertebral body synovial sarcoma is very rare and difficult to diagnose and treat. PMID- 24232696 TI - Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study. AB - Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants of COPD exacerbations in our 5-year observational cohort study which had a very low exacerbation frequency. A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: the patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, or requiring hospital admission. Exacerbation frequency (events per person per year) was 0.78 +/- 1.16, 0.24 +/- 0.47, 0.20 +/- 0.43, 0.13 +/- 0.28 and 0.06 +/- 0.19 for subjective complaint and symptom, prescription, antibiotic and hospital admission definitions, respectively. Exacerbation events did not significantly affect the annual decline in forced expiratory volume in 1 s. A high St George's Respiratory Questionnaire total score, especially activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency and development of recurrent exacerbations. Despite the low exacerbation frequency in our cohort, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations. PMID- 24232697 TI - Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. AB - Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be adequately quantified by analysing one single variable. The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis. This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-cause mortality after radiological diagnosis. A logistic regression analysis was used to select the variables included in the final score. The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2 points); presence of chronic colonisation by Pseudomonas aeruginosa (C, dichotomic, maximum value 1 point); radiological extension (E, number of lobes affected, cut off two lobes, maximum value 1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1 point) to construct the FACED score. The validation cohort confirmed the score's validity. We conclude that this easy-to-use multidimensional grading system proved capable of accurately classifying the severity of bronchiectasis according to its prognosis. PMID- 24232698 TI - LUNOKID: can numerical American Thoracic Society/European Respiratory Society quality criteria replace visual inspection of spirometry? AB - The gold standard for assessing quality of forced expiratory manoeuvres is visual inspection by an expert. American Thoracic Society/European Respiratory Society numerical quality criteria (NQC) include back-extrapolated volume (BEV), repeatability and forced expiratory time (FET). Equipment currently available provides feedback tempting the investigator to use NQC as pass-fail criterion. To investigate whether using NQC instead of visual acceptability is a valid option, we analysed data from a multicentre national reference study in Germany of children aged 4-18 years. Spirometry was performed under field conditions. Receiver operating characteristic analysis was used to assess performance of BEV, repeatability, FET and a combination thereof in relation to visual acceptability. We included data from 3133 healthy Caucasians in the analyses; 72% delivered at least two visually acceptable manoeuvres. Of these, 59% would have been rejected based on combined NQC, mainly because the FET criterion was not feasible. Specificity of the NQC was generally low (BEV 10%, repeatability 30% and FET 50%). Receiver operating characteristic analysis showed that a combination of the three measures could reach at best a sensitivity of 90% and specificity of 56%. We conclude that visual control is mandatory and NQC may help obtain the best possible results, but a fixed cut-off for FET should be abandoned. PMID- 24232699 TI - Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea. AB - There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in epsilon2 carriers and the epsilon3/epsilon3 genotype only. Nevertheless, the epsilon4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk epsilon4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic epsilon4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA. PMID- 24232700 TI - Bronchial valve treatment for pulmonary air leak after anatomical lung resection for cancer. AB - A persistent post-operative pulmonary expiratory air leak after an anatomical pulmonary resection is usually managed conservatively, but can be associated with significant morbidity and increased costs. The use of bronchial valves is a minimally invasive method that may be an effective and safe treatment in this setting. In a prospective study, the clinical efficacy of intrabronchial valve treatment in patients with a prolonged persistent pulmonary air leak after anatomical surgical resection for cancer was investigated. 10 out of 277 patients with anatomical pulmonary resection for cancer were included, and 90% were scheduled for valve treatment. We demonstrated an air leak cessation at a median of 2 days after valve placement, which resulted in chest tube removal at a median of 4 days after valve placement. Elective removal of the intrabronchial valves could be safely planned 3 weeks after valve implantation. Lung function alteration associated with airway occlusion by valves was limited. Intrabronchial valve treatment with the aid of a digital thoracic drainage system is an effective and safe therapy for patients with a prolonged pulmonary air leak after anatomical lung resection for cancer. PMID- 24232701 TI - Effects of weight loss on asthma control in obese patients with severe asthma. AB - Studies on the effects of weight loss in patients with asthma are scarce. No studies have been performed in patients with severe asthma. Therefore, the aim of the present study was to assess the impact of weight loss in patients with severe asthma associated with obesity. This was an open, prospective, randomised study of two parallel groups, in patients with severe uncontrolled asthma and moderate obesity. The primary outcome was the level of asthma control 6 months after initiation of the weight reduction programme, quantified using the Asthma Control Questionnaire (ACQ). We evaluated clinical parameters, lung function, markers of airway inflammation and circulating cytokines. 22 patients were randomised to undergo treatment for obesity and 11 to the control group. The weight reduction programme was associated with significant improvements in asthma control (mean +/ se ACQ score 3.02 +/- 0.19 to 2.25 +/- 0.28 in the treatment group versus 2.91 +/- 0.25 to 2.90 +/- 0.16 in the controls, p=0.001). This improvement was not accompanied by changes in markers of airway inflammation or bronchial reactivity, but by an increase in forced vital capacity. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation. PMID- 24232702 TI - emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension. AB - The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short, validated instrument that can be used in routine clinical practice. Interviews were conducted with 30 PH patients to derive 32 statements, which were presented as a semantic differential six-point scale (0-5), with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model. 226 patients (mean age 55.6+/-14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test-retest (intraclass correlation coefficient 0.95, n=33) and internal consistency (Chronbach's alpha=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001). The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use. PMID- 24232703 TI - Severe pulmonary embolism decreases plasma L-arginine. PMID- 24232704 TI - Proinflammatory cytokine levels are linked to death in pulmonary arterial hypertension. PMID- 24232705 TI - Mycoplasma pneumoniae infection is associated with subacute cough. PMID- 24232706 TI - Inspiratory resistance decreases limb blood flow in COPD patients with heart failure. PMID- 24232707 TI - Role of activin-A in cigarette smoke-induced inflammation and COPD. AB - Activin-A is a pleiotropic cytokine belonging to the transforming growth factor beta superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cells in vitro. Next, activin-A signalling was antagonised in vivo by administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks. Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice. These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD. PMID- 24232708 TI - Asthma affects time to pregnancy and fertility: a register-based twin study. AB - Coexistence of infertility and asthma has been observed clinically. Therefore, we investigated the association between asthma and delayed pregnancy in a nationwide population-based cohort of twins. A cohort of 15 250 twins living in Denmark (aged 12-41 years) participated in a questionnaire study including questions about the presence of asthma and fertility. Differences in time to pregnancy and pregnancy outcome were analysed in subjects with asthma, allergy and in healthy individuals using multiple regression analysis. Asthma was associated with an increased time to pregnancy, the percentage of asthmatics with a time to pregnancy >1 year was 27% versus 21.6% for non-asthmatics (OR (95% CI) 1.31 (1.1 1.6); p=0.009). The association remained significant after adjustment for age, age at menarche, body mass index and socioeconomic status (OR (95% CI) 1.25 (1.0 1.6); p=0.05), and was more pronounced in those >30 years of age (32.2% versus 24.9%, OR (95% CI) 1.44 (1.1-1.9); p=0.04). Untreated asthmatics had a significant increased risk of prolonged time to pregnancy compared to healthy individuals (OR (95% CI) 1.79 (1.20-2.66); p=0.004), while asthmatics receiving any kind of treatment for asthma tended to have a shorter time to pregnancy than untreated asthmatics (OR 1.40; p=0.134). Asthma prolongs time to pregnancy. The negative effect of asthma on fertility increases with age and with disease intensity, indicating that a systemic disease characterised by systemic inflammation also can involve reproductive processes. PMID- 24232709 TI - Artificial insertion of a dominant gene for resistance to avian leukosis virus into the germ line of the chicken. AB - This report describes the unique biological properties of a transgenic chicken line that contains a defective avian leukosis virus (ALV) proviral insert that we call alv6. Chick embryo fibroblasts (CEF) containing this insert express subgroup A envelope glycoprotein since they yield focus-forming pseudotype virus when co cultivated with transformed quail cells expressing envelope-defective Bryan high liter Rous sarcoma virus (RSV). In addition, these cells display high interference to subgroup A RSV but not to subgroup B RSV infection. Chickens containing this insert are highly resistant to pathogenic subgroup A ALV infection, but show little immunological tolerance to subgroup B ALV infection. Thus we have artificially inserted a dominant gene for resistance to avian leukosis infection into the chicken germ line. PMID- 24232710 TI - Phenotypic and karyotypic status of Beta vulgaris plants regenerated from direct organogenesis in petiole culture. AB - A method for high frequency in vitro regeneration from petiole explants was tested on nine breeding lines of Beta vulgaris L. from the haploid, diploid and tetraploid levels. Regenerants could be obtained without a callus step, from excised petioles derived either from axillary buds sprouted in vitro or from field grown plants, by plating the explants on MS medium supplemented with TIBA (2,3,5-triiodobenzoic acid) and BAP (6-Benzylaminopurine). The multiple shoots obtained were then rooted in vitro and transferred to soil. In some cases, these adventitious shoots were also used as a petiole explant source for further petiole culture cycles, and the phenotypic characteristics and ploidy status of the regenerants were investigated after one or three petiole culture cycles. Conventional shoot apex culture was used as an in vitro control. Phenotypic variations such as differences in morphology and changes in in vitro growth behaviour, were noticed. Chloroplast and chromosome counts indicated that the alterations in morphogenetic pathway could not be explained by the occurrence of gross cytogenetic abnormalities such as aneuploidy or myxoploidy. Our results suggest that the altered morphology is caused by the presence of the exogenous antiauxin (TIBA) during the in vitro phase. Following transfer to the greenhouse, none of these variations persisted and cytogenetic analyses revealed karyotypic stability in all the plants studied, even after three petiole culture cycles. An assessment of the in vitro petiole culture method as a true-to-type multiplication method for Beta vulgaris is made. PMID- 24232711 TI - Transfection of germinating barley seed electrophoretically with exogenous DNA. AB - A method is described for transfection (genetic transformation) of barley caryopsis electrophoretically with DNA. beta-Glucuronidase activity was detected after the electrophoretic transfection with plasmid pBI221 DNA carrying the cauliflower mosaic virus promotor and bacterial beta-glucuronidase coding sequence. Electrophoretic transfection is evidently effective with pieces of callus and seeds of many plants. PMID- 24232712 TI - Accuracy and selection success in yield trial analyses. AB - Yield trials serve research purposes of estimation and selection. Order statistics are used here to quantify the successes or problems to be expected in selection tasks commonly encountered in breeding and agronomy. Greater accuracy of yield estimates implies greater selection success. A New York soybean yield trial serves as a specific example. The Additive Main effects and Multiplicative Interaction (AMMI) statistical model is used to increase the accuracy of these soybean yield estimates, thereby increasing the probability of successfully selecting, on the basis of the empirical yield data, that genotype which has the maximum true mean. The statistical strategy for increasing accuracy is extremely cost effective relative to the alternative strategy of increasing the number of replications. Better selections increase the speed and effectiveness of breeding programs, and increase the reliability of variety recommendations. Selection tasks are frequently more difficult than may be suspected. PMID- 24232713 TI - Cellular genetic study of a somatic instability in a tobacco mutant: in vitro isolation of valine-resistant spontaneous mutants. AB - A chlorophyll-deficient mutant line of tobacco (Nicotiana tabacum), named tl, displays spontaneously on leaves green, white, and twinned green/white somatic variations at high frequencies (10(-3) to 10(-2)). The frequency of cell events leading to the somatic variations has been shown to be closely dependent on the stage of differentiation of cells during plant development. The activity of transposable elements is suspected in the tl genotype, and a study of its mutagenic ability was performed by selecting in vitro new mutant cellular types. The cellular marker chosen was the resistance to toxic doses of valine conferred by a permeation deficiency. A reproducible method allowing efficient selection of valine-resistant mutant clones from haploid tobacco mesophyll protoplast-derived cells was used. In 10 out of 12 experiments, the frequency of spontaneous valine resistant clones obtained with the wild-type control was null for cell populations tested to the 10(6). On the other hand, spontaneous valine-resistant clones were repeatedly isolated at variable and sometimes high frequencies (greater than 10(-3)) from cell populations of the tl type. Valine resistance of plants regenerated from these clones was transmitted to the progeny as a single monogenic mutation. These results indicate an increased mutagenic ability of the tl genotype, as compared to the wild-type line. PMID- 24232714 TI - Inheritance patterns of erucic acid content in populations of Brassica napus microspore-derived spontaneous diploids. AB - The levels of erucic acid and other fatty acids in seeds of microspore-derived spontaneous diploid plants from crosses between low and high erucic acid parents were examined. The analysis confirmed that erucic acid is simply inherited and is determined by two genes that act in an additive manner. The effects of the genes for erucic acid on the levels of the other fatty acids was also determined and many significant correlations were found. In particular, erucic acid levels were negatively correlated with oleic acid and linoleic acid levels. The study also illustrates several advantages of using haploidy to analyze the inheritance of agronomically important traits. In particular, the number of phenotypic classes is smaller in androgenic populations and differences between classes are greater than in an F2 population. PMID- 24232715 TI - Multivariate analyses of polypeptide synthesis in developing maize embryos. AB - Variation in polypeptide synthesis was examined in developing maize embryos of two inbred and two hybrid genotypes. Multivariate analyses were used to evaluate the variation among two-dimensional, electrophoretic separations of polypeptides. Several features of the data set were revealed. Similar developmental patterns were exhibited by all genotypes and no evidence was obtained for differential rates of development for inbreds and hybrids. The differential synthesis of two subsets of polypeptides during embryo development was observed. The multivariate methods employed in this study were a valuable aid in interpreting the results from a large and complex data set. PMID- 24232716 TI - Optimization of recurrent selection on the phenotypic value of doubled haploid lines. AB - Three methods of recurrent selection using doubled haploids (DH) are compared with the same resources: individual line selection (with one DH line per plant), selection between and within families, and selection index of family and line within family values. It seems that for low heritabilities at the individual level, the selection index method is the most efficient method, followed by the selection between and within families. Because of the difficulty in optimizing selection intensities, the selection between and within families can be less efficient than individual line selection. For very low heritabilities, it will be better to use selection index with a relatively low number of lines per haploidized plant, to minimize the rate of decrease of the effective population size. For a large range of situations, recurrent selection with only one DH line per plant seems one of the more efficient and the simpler methods. PMID- 24232717 TI - Segregation, viral phenotype, and proviral structure of 23 avian leukosis virus inserts in the germ line of chickens. AB - We have artificially introduced 23 avian leukosis virus (ALV) proviral inserts into the chicken germ line by injection of wild-type and recombinant subgroup A ALV near the blastoderm of fertile eggs just before incubation. Eight viremic males were identified as germline mosaics because they transmitted proviral DNA to their generation 1 (G-1) progeny at a low frequency. Eleven female and 9 male G-1 progeny carried 23 distinct proviruses that had typical major clonal proviral host DNA junction fragments detectable after digestion of their DNA with SacI, Southern blotting and hybridization with a probe representing the complete ALV genome. These proviruses, identified by their typical proviral-host DNA junction fragments, were transmitted to approximately 50% of their G-2 progeny after mating the G-1 parents to a line of chickens lacking endogenous ALV proviral inserts. One G-1 female carried 2 proviruses and another 3. The proviruses appeared to be scattered throughout the genome. One of the 14 proviruses carried by females was on the sex (Z) chromosome. Two of the 3 proviruses carried by a single G-1 female were linked with a recombination frequency of about 0.20. Twenty-one of the proviruses coded for infectious ALV. Two proviruses coded for envelope glycoprotein, and cell cultures carrying them were relatively resistant to subgroup A sarcoma virus, but failed to produce infectious ALV. One of these proviruses coded for internal gag proteins, had a deletion in pol, but produced non-infectious virus particles. The other failed to code for gag proteins and had no detectable internal deletions nor did it produce virus particles. Thus, we have shown that replication-competent ALV can artificially infect germ-line cells and that spontaneous defects in the inherited proviruses occur at a rather low rate. PMID- 24232718 TI - Genetic variability and advance under four selection procedures in wheat pedigree breeding programme. AB - Four methods of generation advance (SPS, SSD, BP and MMS) were compared in F3 and F4 generations. In the F3 generation, the SPS and SSD methods of generation advance proved superior to the BP and MMS methods for grain yield per plant and for at least one of the yield component traits. The F3 SSD population did not differ significantly from the F3 SPS for any of the traits. However, the F3 SSD population retained more range and cv for different traits than with other methods of generation advance. F4 progenies derived from F3 SSD population were significantly superior for grain yield than lines derived from the other three F3 populations. The MMS method of generation advance proved useful for increasing the 1,000-grain weight for which initial selection was made. PMID- 24232719 TI - Production of normal, germinable and viable pollen from in vitro-cultured maize tassels. AB - Immature tassel meristems (1.0-1.5 cm long) of Zea mays L. inbred, Oh43, and single cross hybrid, Se60, cultured on a nutrient liquid medium underwent extensive development through to maturity and produced normal, mature, trinucleate pollen grains. The grains germinated on nutrient agar and on receptive silks and also produced viable kernels. No differences were observed between in vitro-produced pollen and in vivo pollen (pollen from greenhouse-grown plants) in characteristics such as pollen size, in vitro and in situ germination, and pollen tube growth in vitro. The kernels produced with in vitro pollen grew into mature plants (in vitro plants) which were similar to in vivo plants (plants produced with in vivo pollen), with no significant differences for all the morphological characteristics measured, and no phenotypic and cytological abnormalities. Gel electrophoresis of polypeptides revealed no major differences between in vitro and in vivo seedlings. This demonstration of fertilization and production of normal, uniform plants with pollen from cultured tassels has significant potential in basic and applied research studies. PMID- 24232720 TI - Performance of recombinant inbred lines in Brussels sprouts (Brassica oleracea var. gemmifera). AB - Performance of a random array of recombinant inbred lines derived by single seed descent from five different source populations of Brussels sprouts (Brassica oleracea var. gemmifera) is presented. A total of 2,356 lines were tested in trials during 1985 and 1986. Three of the source populations were derived from double crosses between F1 hybrids. These hybrids show a considerable heterotic advantage over their inbred parents for the most important agronomic traits. The recombinant inbred lines performed, on average, less well than the parental inbred material, indicating that additive x additive genie interactions may make a significant contribution to the performance of current inbred material. Nevertheless, the very large variation among the recombinant inbred lines permitted many lines to be identified which outperformed the best parental inbred for all traits. Two lines outperformed the reference F1 hybrid, Gower, for an index that included marketable yield and quality. Consideration was also given to the dangers of misinterpreting phenotypically based proportions. Accordingly, response equations were used to ascertain the real genetic progress that was made. Advance seemed small when compared with the large heterotic effect, which is consistent with the segregation of a large number of loci. The distribution of the recombinant inbred lines was compared to predictions made from early generation trials. There was broad agreement but significant discrepancies existed which, it is suggested, may arise from the effects of genotype environment interactions. PMID- 24232721 TI - Use of molecular markers for monitoring fungi involved in stalk rot of corn. AB - Separate genes conferring antibiotic drag resistance have been inserted into Fusarium graminearum and Fusarium moniliforme. These organisms are associated with stalk rot of corn, a disease of uncertain cause. Antibiotic resistant fungi were obtained by developing a gene transfer system using whole cells as recipients for DNA. Hygromycin B and benomyl-resistant colonies were isolated by treating fungal tissue with lithium acetate and adding plasmid vectors containing the respective genes which give drug resistance. The DNA was stably integrated into the fungal chromosome. Following plant inoculation, disease symptoms developed and the isolates were recovered on selective medium. In each case, these fungi retained the transformed phenotype, although extensive rearrangements and/or deletions occurred. Specific molecular tagging allows detailed studies of this interaction and should be of general use in situations involving complex multiple pathogen diseases. PMID- 24232722 TI - Recombination among genes at the L group in flax conferring resistance to rust. AB - Fourteen of the known genes conferring resistance to rust in flax occur in the L group, and recombinational analysis has been used to study their fine structure. Three important features were observed. (a) Similar to the findings of Shepherd and Mayo, only susceptible recombinants were detected among the testcross progeny of 11 of the 15 heterozygotes involving pairs of L genes. Some of these recombinants showed variation in the degree of their susceptibility and appeared to be unstable in nature. (b) A new class of recombinants exhibiting a modified type of resistance was recovered. They occurred rarely but consistently, with frequencies similar to that of susceptible recombinants. (c) Rare resistant plants occurred among the progeny of susceptible recombinants. In each case, the specificity of the resistant plant corresponded to only one of the parental types. The relative roles of seed contamination, mutation, recombination and the transposition of genetic elements are discussed to account for these features. PMID- 24232723 TI - Efficient selection of somatic hybrids in Nicotiana tabacum L. using a combination of drug-resistance markers introduced by transformation. AB - Kanamycin resistance and chloramphenicol resistance were introduced separately to two different tobacco plants (Nicotiana tabacum L.) by Agrobacterium-mediated transformation. Leaf mesophyll protoplasts were prepared from the progeny of these transformants and were subjected to electrofusion. On the 10th day and the 20th day after the fusion treatment, respectively, kanamycin (100 mg/l) and chloramphenicol (30 mg/l) were added to the suspension of protoplasts. The parental protoplasts and an unfused mixture of these protoplasts failed to form colonies when this selection procedure was employed. However, three independent fusion experiments yielded more than 7000 doubleresistant colonies with a frequency between 0.30% and 0.54%. All of the surviving colonies showed continuous growth in the presence of the two antibiotics. The majority of regenerated plants resembled, morphologically, a tetraploid tobacco plant, and their somatic chromosome numbers were 2n=96. The leaf segments from these putative somatic hybrids formed calli and proliferated vigorously on a medium that contained both antibiotics. Southern hybridization permitted the detection of the DNA fragments that conferred kanamycin and chloramphenicol resistance on these somatic hybrid plants. The system described here can be considered to be a universal system for the selection of somatic hybrids and is applicable to various combinations of protoplasts in which pre-selected genetic markers are absent. PMID- 24232724 TI - DNA hybridization analyses of a Gossypium allotetmploid and two closely related diploid species. AB - The DNAs of two diploid species of Gossypium, G. herbaceum var. africanum (A1 genome) and G. raimondii (D5 genome), and the allotetraploid species, G. hirsutum (Ah and Dh genomes), were characterized by kinetic analyses of single copy and repetitive sequences. Estimated haploid genome sizes of A1 and D5 were 1.04 pg and 0.68 pg, respectively, in approximate agreement with cytological observations that A genome chromosomes are about twice the size of D genome chromosomes. This differences in genome size was accounted for entirely by differences in the major repetitive fraction (0.56 pg versus 0.20 pg), as single copy fractions of the two genomes were essentially identical (0.41 pg for A1 and 0.43 pg for D5). Kinetic analyses and thermal denaturation measurements of single copy duplexes from reciprocal intergenomic hybridizations showed considerable sequence similarity between A1 and D5 genomes (77% duplex formation with an average thermal depression of 6 degrees C). Moreover, little sequence divergence was detectable between diploid single copy sequences and their corresponding genomes in the allotetraploid, consistent with previous chromosome pairing observations in interspecific F1 hybrids. PMID- 24232725 TI - Experimental study of the influence of errors of genetic correlation estimates on unrestricted, optimum, and desired gains selection indices. AB - Effects of errors in estimates of the genetic correlation on the accuracy of unrestricted, optimum, and desired gains selection indices were examined experimentally in Tribolium castaneum. Three lines were selected for three generations for pupal weight at 21 days and adult weight at 31 days, using unrestricted (I9), optimum (O9), and desired gains (G9) index selection methods. The genetic correlation between pupal and adult weights in the base population was 0.95. The optimum index was designed to set the response of pupal weight by a fixed amount, while in the desired gains index the responses of pupal and adult weights were specified as being equal to 3?1. Three other indices were constructed using a deliberately incorrect genetic correlation (0.25), i.e., unrestricted (I2), optimum (O2), and desired gains (G2). Responses observed in unrestricted index lines (I9 versus I2) and optimum index lines (O9 versus O2) did not differ significantly, even though lines I9 and I2 differed in a practical sense. Responses in desired gains index lines (G9 versus G2) differed significantly. Responses obtained for aggregate genotype (pupal weight + adult weight) and for the component traits were greater in line I9 than those obtained in line I2. Responses obtained in the O9 and O2 lines for pupal and adult weights were similar, while those obtained in the G9 and G2 lines were similar for pupal weight but not (P<0.05) for adult weight. Therefore, underestimation of the genetic correlation seems to affect the efficiency of a desired gains index more than that of unrestricted or optimum indices. PMID- 24232726 TI - Maternal effects and generation mean analysis of seed-oil content in cotton (Gossypium hirsutum L.). AB - The nature of gene action and of maternal influence governing cottonseed oil attributes were determined with four lines, two each with high and low seed-oil percentage. For this purpose, P1, P2, F0, F1, F2 and alternative sets of BC1 and BC2 generations were analysed in six cross-combinations and their reciprocals. Marginal extents of heterosis for seed-oil percentage were noticeable in F1, with inbreeding depression in F2. Data from reciprocal backcrosses provided evidence in favour of maternal rather than cytoplasmic effects of seed-oil development. Relatively higher extents of heterosis, sizeable inbreeding depression and reciprocally unequal F2 averages were characteristic of the seed index trait, which often showed a reversal of effects from F1 to F2. Reverse reciprocal backcrosses exhibited some differences, including greater resemblance between the types, (A/B)A and (B/A)A, in addition to variable dose effects in seed index. Thus, the differences between F1 seed index values were not due to cytoplasmic influence. Positive heterotic effects for seed-oil index, especially among the backcrosses, ranged between 16.08% and 47.29% over midparent averages. Genetic component estimates from analysis of similar sets of crosses differing only in reciprocal backcrosses, and also from sets of reciprocal crosses between any two parental combinations, were inconsistent. Scaling tests detected presence of epistasis within and between a majority of cross-combinations. Despite reciprocal differences, additive gene effects for seed-oil percentage were significant in 7 out of 24 crosses, representing high x low, low x high and low x low seed-oil parents. Those were, however, accompanied by significant dominance effects of higher order. In crosses involving low seed-oil percentage parents SA1060 and SA229, all six components were detected significant, with opposite effects of dominance and dominance x dominance epistatic components. Significant additive components were also detected for seed index and seed-oil index in 7 and 5 out of 24 crosses, respectively. In the inheritance of seed index and seed-oil index, dominance effects were more important. Epistatic components of additive x additive, and to a lesser extent, those of dominant x dominant were found significant. PMID- 24232727 TI - Allelic relationship of four male sterility genes and nucleo-cytoplasmic interactions in the expression of male sterility in pearl millet, Pennisetum americanum (L.) leeke. AB - Male sterility genes isolated in four inbred lines of pearl millet were found allelic. The differences between male fertile and male sterile phenotypes is mainly due to a single gene. Presence of a dominant gene (Ms) resulted in male fertility and double recessiveness (ms ms) in male sterility. However, genic male sterility (GMS) in Pennisetum is not a simply inherited case of monogenic recessive condition but is influenced by cytoplasmic and several nuclear factors. In a male sterile, the stage at which the male sterility gene is expressed during the development of the male gametophyte resulting in breakdown of the cells is influenced by cytoplasmic and other nuclear factors. Two types of cytoplasm, C-1 and C-2, are recognized. Presence of any two recessive male sterility alleles in C-1 led to breakdown of male development before differentiation of an archesporium in the anther (Arc-type); in C-2 cytoplasm, degeneration started during meiosis with fusion of meiocytes and syncyte formation (Syn-type), or at post-meiotic stages terminating in abortion of microspores before first pollen mitosis (PGM type). The triggering of activity of recessive male sterility genes in C-2 cytoplasm appeared to be regulated by two nuclear factors, R 1 and R 2 with duplicate gene action. Recessiveness for both the R factors in C-2 cytoplasm resulted in PGM-type expression. The action of R 1 and R 2 is specific to C-2 cytoplasm. Mutation of cytoplasm from C-1 to C-2 and C-2 to C-1 was observed. PMID- 24232728 TI - Some physicochemical properties of rice mitochondrial DNA. AB - Certain physicochemical properties of rice mitochondrial DNA (mtDNA) were determined. Certain low-molecular-weight mtDNA bands were found in addition to the major mtDNA band. Rice mtDNA appeared in the electron microscope as a collection of linear molecules with heterogeneous length in the range of 1-156 kb. The major distribution area was 60-105 kb. A small fraction (less than 5%) of rice mtDNA was found in the form of a circular molecule. Some molecules had the appearance of being supercoiled. Replication fork structures were found in both circular and linear mtDNA molecules. In one rice species, Jin Nante, 15 different circular molecules were found. Rice mtDNA was digested with different restriction enzymes. The total molecular weight of rice mtDNA was calculated to be about 300 kb according to the data of restriction enzyme digestion and electron microscopy. PMID- 24232729 TI - Unstable expression of a soybean gene during seed coat development. AB - The R gene of soybean is involved in anthocyanin synthesis in the seed coat, and its r-m allele conditions a variegated distribution of black spots and/or concentric rings of pigment superimposed on an otherwise brown seed coat. We describe an unusual feature of r-m that causes expression at the R locus to switch between active and inactive phases both somatically and germinally. Non heritable somatic changes of the allele produce single plants containing mixtures of seed with different coat colors (black+striped or brown+striped). Heritable changes of the r-m allele are manifested in progeny plants which produce all black seed or all brown seed. Surprisingly, subsequent generations from revertant sublines show continued instability of the allele such that brown revertants (r*/r*) or homozygous black seed revertants (R*/R*) can give rise to striped or striped+black-seeded plants. Thus, the revertants produced by the r-m allele are not stable but interconvert between all three forms (R*, r*, and r-m) at detectable frequencies. Mutability of the r-m allele in a different genetic background has also been found after inter-crossing various soybean genotypes. PMID- 24232730 TI - An isoenzyme study in the genus Lotus (Fabaceae). Experimental protocols and genetic basis of electrophoretic phenotype. AB - An isoenzyme survey of some taxa in the genus Lotus (Fabaceae) was undertaken to increase the number of genetic markers available to breeders and to students of Lotus phylogeny. Twenty-one enzymes were examined using starch gel electrophoresis and nine buffer systems. Clear, consistent banding patterns were obtained for PGI, TPI, MDH, IDH (NADP), PGM, 6-PGDH, and ME. Clear but inconsistent banding patterns were obtained for FDP, G3PDH (NADP), beta-EST, LAP, MDH, DIA, and NADHDH. Phenotypes of the seven consistently resolved enzyme systems were obtained for different tissues for each of several genotypes at different stages of development. Variation in enzyme phenotypes of the same individuals under different growth conditions indicated the presence of different isozymic forms of these enzymes. Shoot tissue of plants over 6 weeks of age was found to be suitable material for further genetic studies, since phenotype for this tissue was constant despite changes in growing conditions. A formal genetic analysis of segregation and/or recombination of allozymes for the enzymes PGM, TPI, MDH, IDH, and 6-PGDH was undertaken. Isoenzyme phenotypes were examined for the diploids L. alpinus Schleich., L. burttii Sz. Borsos, L. conimbricensis Brot., L. ornithopodioides L., L. tennis Waldst. et Kit., and L. uliginosus Schkuhr; and for the diploid interspecific hybrids L. alpinus x L. conimbricensis, L. burttii x L. ornithopodioides, and L. japonicus x L. alpinus. Several new loci were identified for Lotus, namely, Idh1, Idh2, Mdh3, Pgi1, Pgi2, Tpi1, Tpi2, and 6-Pdgh1. Duplications of loci of IDH, MDH, PGI, and 6-PGDH were detected in the diploid (2n=12) interspecific hybrid L. japonicus x L. alpinus. PMID- 24232731 TI - Anti-obesity effects of gut microbiota are associated with lactic acid bacteria. AB - The prevalence of obesity is rapidly becoming endemic in industrialized countries and continues to increase in developing countries worldwide. Obesity predisposes people to an increased risk of developing metabolic syndrome. Recent studies have described an association between obesity and certain gut microbiota, suggesting that gut microbiota might play a critical role in the development of obesity. Although probiotics have many beneficial health effects in humans and animals, attention has only recently been drawn to manipulating the gut microbiota, such as lactic acid bacteria (LAB), to influence the development of obesity. In this review, we first describe the causes of obesity, including the genetic and environmental factors. We then describe the relationship between the gut microbiota and obesity, and the mechanisms by which the gut microbiota influence energy metabolism and inflammation in obesity. Lastly, we focus on the potential role of LAB in mediating the effects of the gut microbiota in the development of obesity. PMID- 24232733 TI - Empirically Based Profiles of the Early Literacy Skills of Children With Language Impairment in Early Childhood Special Education. AB - The purpose of this study was to empirically determine whether specific profiles characterize preschool-aged children with language impairment (LI) with respect to their early literacy skills (print awareness, name-writing ability, phonological awareness, alphabet knowledge); the primary interest was to determine if one or more profiles suggested vulnerability for future reading problems. Participants were 218 children enrolled in early childhood special education classrooms, 95% of whom received speech-language services. Children were administered an assessment of early literacy skills in the fall of the academic year. Based on results of latent profile analysis, four distinct literacy profiles were identified, with the single largest profile (55% of children) representing children with generally poor literacy skills across all areas examined. Children in the two low-risk categories had higher oral language skills than those in the high-risk and moderate-risk profiles. Across three of the four early literacy measures, children with language as their primary disability had higher scores than those with LI concomitant with other disabilities. These findings indicate that there are specific profiles of early literacy skills among children with LI, with about one half of children exhibiting a profile indicating potential susceptibility for future reading problems. PMID- 24232732 TI - Discovering disease-disease associations by fusing systems-level molecular data. AB - The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion. PMID- 24232734 TI - Redefining Individual Growth and Development Indicators: Phonological Awareness. AB - Learning to read is one of the most important indicators of academic achievement. The development of early literacy skills during the preschool years is associated with improved reading outcomes in later grades. One of these skill areas, phonological awareness, shows particular importance because of its strong link to later reading success. Presented here are two studies that describe the development and revision of four measures of phonological awareness skills: Individual Growth and Development Indicators Sound Blending, Syllable Sameness, Rhyming, and Alliteration 2.0. The authors discuss the measure development process, revision, and utility within an early childhood Response to Intervention framework. PMID- 24232735 TI - The synthesis and characterization of hydroxyapatite-beta-alanine modified by grafting polymerization of gamma-benzyl-L-glutamate-N-carboxyanhydride. AB - In this study, hydroxyapatite (HAP) was surface-modified by the addition of beta alanine (beta-Ala), and the ring-opening polymerization of gamma-benzyl-L glutamate-N-carboxy-anhydride (BLG-NCA) was subsequently initiated. HAP containing surface poly-gamma-benzyl-L-glutamates (PBLG) was successfully prepared in this way. With the increase of PBLG content in HAP-PBLG, the solubility of HAP-PBLG increased gradually and it was ultimately soluble in chloroform. HAP-PLGA with surface carboxyl groups was obtained by the catalytic hydrogenation of HAP-PBLG. In the process of HAP modification, the morphology changes from rod to sheet and from flake to needle. The effect of BLG-NCA concentration on the character of hydroxyapatite-beta-alanine-poly(gamma-benzyl-L glutamate) (HAP-PBLG) was investigated. The existence of amino acids on the HAP surfaces was confirmed in the resulting Fourier transform infrared (FTIR) spectra. The resulting powder X-ray diffraction patterns indicated that the crystallinity of HAP decreased when the ratio of BLG-NCA/HAP-NH2 increased to 20/1. Transmission electron microscopy (TEM) indicated that the particle size of HAP-PBLG decreased significantly and that the resulting particles appeared less agglomerated relative to that of the HAP-NH2 crystals. Furthermore, 1H-NMR spectra and FTIR spectra revealed that hydroxyapatite-beta-alanine-poly (L glutamic acid) (HAP-PLGA) was able to successfully bear carboxylic acid groups on its side chains. PMID- 24232736 TI - Synthesis and anticancer activity of glucosylated podophyllotoxin derivatives linked via 4beta-triazole rings. AB - A series of 4beta-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC50 values ranging from 0.59 to 2.90 MUM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue. PMID- 24232737 TI - Optimization of a pre-MEKC separation SPE procedure for steroid molecules in human urine samples. AB - Many steroid hormones can be considered as potential biomarkers and their determination in body fluids can create opportunities for the rapid diagnosis of many diseases and disorders of the human body. Most existing methods for the determination of steroids are usually time- and labor-consuming and quite costly. Therefore, the aim of analytical laboratories is to develop a new, relatively low cost and rapid implementation methodology for their determination in biological samples. Due to the fact that there is little literature data on concentrations of steroid hormones in urine samples, we have made attempts at the electrophoretic determination of these compounds. For this purpose, an extraction procedure for the optimized separation and simultaneous determination of seven steroid hormones in urine samples has been investigated. The isolation of analytes from biological samples was performed by liquid-liquid extraction (LLE) with dichloromethane and compared to solid phase extraction (SPE) with C18 and hydrophilic-lipophilic balance (HLB) columns. To separate all the analytes a micellar electrokinetic capillary chromatography (MECK) technique was employed. For full separation of all the analytes a running buffer (pH 9.2), composed of 10 mM sodium tetraborate decahydrate (borax), 50 mM sodium dodecyl sulfate (SDS), and 10% methanol was selected. The methodology developed in this work for the determination of steroid hormones meets all the requirements of analytical methods. The applicability of the method has been confirmed for the analysis of urine samples collected from volunteers--both men and women (students, amateur bodybuilders, using and not applying steroid doping). The data obtained during this work can be successfully used for further research on the determination of steroid hormones in urine samples. PMID- 24232738 TI - Synthesis of some green dopants for OLEDs based on arylamine 2,3-disubstituted bithiophene derivatives. AB - A series of green dopants based on 2,2-diphenylvinyl end-capped bithiophene and three different arylamine moieties (9-phenylcarbazole, triphenylamine, and N,N' di-(p-tolyl)benzeneamine) were successfully synthesized by the Suzuki and Wittig coupling reactions. The photophysical properties of these compounds are reported. The strongest PL emitting compound with the 9-phenylcarbazole moiety has been used for fabricating an OLED device with good overall performance. PMID- 24232739 TI - Molecular MRI of atherosclerosis. AB - Despite advances in prevention, risk assessment and treatment, coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western countries. The lion's share is due to acute coronary syndromes (ACS), which are predominantly triggered by plaque rupture or erosion and subsequent coronary thrombosis. As the majority of vulnerable plaques does not cause a significant stenosis, due to expansive remodeling, and are rather defined by their composition and biological activity, detection of vulnerable plaques with x-ray angiography has shown little success. Non-invasive vulnerable plaque detection by identifying biological features that have been associated with plaque progression, destabilization and rupture may therefore be more appropriate and may allow earlier detection, more aggressive treatment and monitoring of treatment response. MR molecular imaging with target specific molecular probes has shown great promise for the noninvasive in vivo visualization of biological processes at the molecular and cellular level in animals and humans. Compared to other imaging modalities; MRI can provide excellent spatial resolution; high soft tissue contrast and has the ability to simultaneously image anatomy; function as well as biological tissue composition and activity. PMID- 24232740 TI - Design, synthesis and cytotoxic activities of novel aliphatic amino-substituted flavonoids. AB - A series of flavonoids 9a-f, 13b, 13d, 13e and 14a-f bearing diverse aliphatic amino moieties were designed, synthesized and evaluated for their cytotoxic activities against the ECA-109, A-549, HL-60, and PC-3 cancer cell lines. Most of the compounds exhibited moderate to good activities. The structure-activity relationships were studied, revealing that the chalcone skeleton is the most preferable for cytotoxic activities. Chalcone 9d was the most promising compound due to its high potency against the examined cancer cell lines (its IC50 values against ECA-109, A549, HL-60 and PC-3 cells were 1.0, 1.5, 0.96 and 3.9 MUM, respectively). PMID- 24232741 TI - Evaluation of garlic cultivars for polyphenolic content and antioxidant properties. AB - Two phenolic compound parameters (total phenolic and flavonoid contents) and 5 antioxidant parameters (DPPH [2, 2-diphenyl-1-picrylhydrazyl] radical scavenging activity, HRSC (hydroxyl radical scavenging capacity), FRAP (ferric ion reducing antioxidant power), CUPRAC (cupric ion reducing antioxidant capacity), and MCA (metal chelating activity) were measured in bulbs and bolts of 43 garlic cultivars. The bulbs of cultivar '74-x' had the highest phenolic content (total phenolic, flavonoids) and the strongest antioxidant capacity (DPPH, FRAP, and CUPRAC), followed by bulbs of cultivar 'Hanzhong purple'; the bulbs of cultivar 'Gailiang' had the lowest phenolic content and antioxidant capacity (FRAP, CUPRAC, MCA). The bolts of 'Hanzhong purple' also had higher phenolic content. Principal components analysis (PCA) separated the cultivars into 3 groups according to phenolic and flavonoid contents and strength of antioxidant activity. The first group had higher HRSC, FRAP, and flavonoid content; the second group had higher total phenolic content and MCA; some cultivars in the third group had higher HRSC and FRAP. All 8 test garlic bulb extracts successfully prevented Human Vascular Endothelial Cell death and significantly prevented reactive-oxygen species (ROS) formation in oxidative stress model, in which cultivar '74-x' had highest protection capability, following by cultivar 'Hanzhong purple', and the bulbs of cultivar 'No. 105 from Korea' had the lower protection capability against cell death and ROS formation. The protection capability in vivo of these garlic cultivars was consistent with their phenolic content and antioxidant capacity. PMID- 24232742 TI - [Minimum thresholds under scrutiny]. AB - Minimum volume thresholds for specific medical treatments have been implemented in Germany since 2004. In the last 9 years the catalogue of procedures, which is determined by the Federal Joint Committee, has changed continuously and currently consists of 8 procedures. In this article the basis of decision making for the enrolment in the catalogue of procedures and the determination of minimum volume thresholds are examined. An overview of systematic reviews was published in 2012 outlining the correlation between the volume components and medical outcome. The body of evidence identified is compared to the current regulatory conditions of the Federal Joint Committee. PMID- 24232744 TI - [Pyloromyotomy of congenital pyloric stenosis : Modified Tan-Bianchi procedure.] AB - The aim was to find a simple and safe surgical technique for pyloromyotomy in infancy. An indication exists in typical clinical symptoms with wave-like vomiting and sonographically confirmed pyloric stenosis. Existing movements in the acid-base-household should be balanced beforehand otherwise there is an increased risk in anesthesia. The operation represents a combination of gasless laparoscopy and open pyloromyotomy according to Tan-Bianchi. Postoperative food intake should be initiated as soon as possible. PMID- 24232745 TI - Early changes in myocardial microcirculation in asymptomatic hypercholesterolemic subjects: as detected by perfusion CT. AB - Intramyocardial microvessels show functional changes in early stages of atherosclerosis prior to epicardial coronary artery stenosis. However, clinical CT does not have adequate spatial resolution to resolve the microvessels. To clinically detect changes in the function of the intramyocardial microcirculation, the spatial heterogeneity of the distribution of myocardial perfusion (F) and intramyocardial microcirculatory blood volume (Bv) was determined by perfusion CT. Two human subject groups were studied: (i) a "Control" group (24) with no risk factors nor evidence of coronary artery disease (CAD), and (ii) an "At-Risk" group (24) with hypercholesterolemia, but no evidence of CAD. In the perfusion CT image, a region of interest (ROI) covering the left ventricular myocardium was subdivided into multiple nested ROI (nROI) of equal size and used to compute F and Bv for each nROI. No significant differences between the groups were demonstrable in overall myocardial F, or Bv. The nROI data showed significantly increased spatial heterogeneity in the "At Risk" group when compared to "Control" subjects. This study demonstrates that subresolution distribution at the microcirculatory level can be quantified with myocardial perfusion CT and significant changes in these parameters occur in hypercholesterolemic subjects before they have developed significant changes in conventional perfusion parameters. PMID- 24232747 TI - A distinct atomic structure-catalytic activity relationship in 3-10 nm supported Au particles. AB - Bulk Au is very inert but Au nanoparticles less than 5 nm in size have been found to be catalytically active for several reactions, in particular for low temperature oxidation of CO. Using high-energy X-ray diffraction coupled with atomic pair distribution function analysis and computer simulations we determine the structure of 3 nm and 10 nm Au particles supported on titania and silica as typical representatives of reducible and irreducible supports, respectively. We find that the synthesis protocol adopted in our work affects strongly and differently the structure of the Au nanoparticles on the different supports. This leads to clearly distinct dependences of the catalytic activity of the nanoparticles on their size. In the case of the silica support the catalytic activity of Au nanoparticles increases and in the case of the titania support it decreases with decreasing nanoparticle size. The experimental results are considered in terms of current theoretical predictions and found to be in good accord with them. PMID- 24232746 TI - Role of the microbiota and antibiotics in primary sclerosing cholangitis. AB - Primary sclerosing cholangitis (PSC) is an idiopathic, progressive, cholestatic liver disease with considerable morbidity and mortality and no established pharmacotherapy. In addition to the long-recognized association between PSC and inflammatory bowel disease, several lines of preclinical and clinical evidence implicate the microbiota in the etiopathogenesis of PSC. Here we provide a concise review of these data which, taken together, support further investigation of the role of the microbiota and antibiotics in PSC as potential avenues toward elucidating safe and effective pharmacotherapy for patients afflicted by this illness. PMID- 24232749 TI - Advances in molecular analysis of biomarkers for autoimmune and carcinogenic diseases. PMID- 24232750 TI - The pivotal role of copper(II) in the enantiorecognition of tryptophan and histidine by gold nanoparticles. AB - Stereoselective amino acid analysis has increasingly moved into the scope of interest of the scientific community. In this work, we report a study on the chiral recognition of D,L-Trp and D,L-His using L -Cys-capped gold nanoparticles (AuNPs) and copper(II) ion. In the L -Cys-capped AuNPs, the thiol group of the amino acid interacts with AuNPs through the formation of Au-S bond, whereas the alpha-amino and alpha-carboxyl groups of the surface-confined cysteine can coordinate the copper(II) ion, which in turn, binds the L- or D-amino acid present in solution forming diastereoisomeric complexes. The resulting systems have been characterized by UV-Vis spectra and dynamic light scattering measurements, obtaining different results for L- and D-Trp, as well as for L- and D-His. The knowledge of the solution equilibria of the investigated systems allowed us to accurately calculate in advance the concentrations of the species presentin solution and to optimize the system performances, highlighting the pivotal role of copper(II) ion in the enantiodiscrimination processes. PMID- 24232751 TI - 3,4-Methylenedioxymethamphetamine (MDMA) and metabolites disposition in blood and plasma following controlled oral administration. AB - 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4 methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two dimensional gas chromatography-mass spectrometry. Specimens were collected up to 3 h post-dose and evaluated for maximum concentration (C max), first detection time (t first), time of C max (t max), and 3-h area under the curve (AUC0-3 h); as well as blood metabolite ratios and blood/plasma ratios. Median blood MDMA and MDA C max were significantly greater (p < 0.0005) than in plasma, but HMMA was significantly less (p < 0.0005). HMA was detected in few blood specimens, at low concentrations. Nonlinear pharmacokinetics were not observed for MDMA or MDA in this absorptive phase, but HMMA C max and AUC0-3 h were similar for both doses despite the 1.6-fold dose difference. Blood MDA/MDMA and MDA/HMMA significantly increased (p < 0.0001) over the 3-h time course, and HMMA/MDMA significantly decreased (p < 0.0001). Blood MDMA C max was significantly greater in females (p = 0.010) after the low dose only. Low-dose HMMA AUC0-3 h was significantly decreased in females' blood and plasma (p = 0.027) and in African-Americans' plasma (p = 0.035). These data provide valuable insight into MDMA blood-plasma relationships for forensic interpretation and evidence of sex- and race-based differential metabolism and risk profiles. Figure Median (interquartile range) blood/plasma 3,4-methylenedioxymethamphetamine (MDMA) (a), 4-hydroxy-3 methoxymethamphetamine (HMMA) (b), and 3,4-methylenedioxyamphetamine (MDA) (c) ratios for 3 h after controlled MDMA administration. Changes over time were significant after the 1.6 mg/kg dose for HMMA and MDA (p = 0.013 and p = 0.021), but not for MDMA. No changes over time were significant after the 1.0 mg/kg dose. Note: y-axes do not begin at 0. *p < 0.05 (low vs. high). PMID- 24232752 TI - The hydraulic safety zone at the base of barley roots. AB - A hydraulic constriction of the vessels occurs at the base of the primary roots of barley (Hordeum vulgare L.). The constriction and consequent hydraulic protection result from an extreme shortening of the vessel elements, leading to the accumulation of perforation plates with simple, broad-rimmed perforations which are smaller than those in normal-length vessel elements. It is compensated for by a local increase in the number of tracheary elements and an increase in their diameter. A similar trend of development was observed both at the base of other seminal roots and at the base of stem-borne adventitious roots. The rate at which compensation for the hydraulic constriction occurs could be of crucial importance for the axial resistance of water transport. PMID- 24232753 TI - Immunochemical studies on the role of the Golgi complex in protein-body formation in rice seeds. AB - Antibodies raised against purified glutelins and prolamines were employed as probes to study the cellular routes by which these proteins are deposited into protein bodies of rice (Oryza sativa L.) endosperm. Three morphologically distinct protein bodies, large spherical, small spherical, and irregularly shaped, were observed, in agreement with existing reports. Immunocytochemical studies showed the presence of glutelins in the irregularly-shaped protein bodies while the prolamines were found in both the large and small spherical protein bodies. Both the large and small spherical protein bodies, distinguishable by electron density and gold-labeling patterns, appear to be formed by direct deposition of the newly formed proteins into the lumen of the rough endoplasmic reticulum (ER). In contrast, glutelin protein bodies are formed via the Golgi apparatus. Small electron-lucent vesicles are often found at one side of the Golgi. Electron-dense vesicles, whose contents are labeled by glutelin antibody gold particles, are commonly observed at the distal side of the Golgi apparatus and fuse to form the irregularly shaped protein bodies in endosperm cells. These observations indicate that the transport of rice glutelins from their site of synthesis, the ER, to the site of deposition, the protein bodies, is mediated by the Golgi apparatus. PMID- 24232754 TI - Fatty-acid synthesis in chloroplasts from mustard (Sinapis alba L.) cotyledons: formation of acetyl coenzyme A by intraplastid glycolytic enzymes and a pyruvate dehydrogenase complex. AB - Chloroplasts from the cotyledons of mustard (Sinapis alba L.) seedlings were isolated on Percoll gradients, and showed a high degree of intactness (92%) and purity as judged by electron microscopy and marker-enzyme analysis (cytoplasmic contamination lower than 0.4% on a protein basis). The chloroplasts synthesized longchain fatty acids from both precursors [1-(14)C] acetate and [2 (14)C]pyruvate; maximum incorporation rates were 96 nmol.(mg Chl)(-1).h(-1) for acetate and 213 nmol.(mg Chl)(-1).h(-1) for pyruvate. Acetyl-CoA-producing enzymatic activities, namely acetyl-CoA synthetase (EC 6.2.1.1.) and a pyruvate dehydrogenase complex, showed specific activities of 14.8 nmol.(mg protein)( 1).min(-1) and 18.2 nmol.(mg protein)(-1).min(-1), respectively. The glycolytic enzymes phosphoglyceromutase (EC 2.7.5.3) phosphopyruvate hydratase (EC 4.2.1.11) and pyruvate kinase (EC 2.7.1.40) were all found to be components of these chloroplasts, thus indicating a possible pathway for intraplastid acetyl-CoA formation. PMID- 24232755 TI - Anatomical analysis of growth and developmental patterns in the internode of deepwater rice. AB - Submergence of the stem induces rapid internodal elongation in deepwater rice (Oryza sativa L. cv. "Habiganj Aman II"). A comparative anatomical study of internodes isolated from airgrown and partially submerged rice plants was undertaken to localize and characterize regions of growth and differentiation in rice stems. Longitudinal sections were examined by light and scanning-electron microscopy. Based on cell-size analysis, three zones of internodal development were recognized: a zone of cell division and elongation at the base of the internode, designated the intercalary meristem (IM); a zone of cell elongation without concomitant cell division; and a zone of cell differentiation where neither cell division nor elongation occur. The primary effects of submergence on internodal development were a threefold increase in the number of cells per cell file resulting from a decrease in the cell-cycle time from 24 to 7 h within the IM; an expansion of the cell-elongation zone from 5 to 15 mm leading to a threefold greater final cell length; and a suppression of tissue differentiation as indicated by reduced chlorophyll content and a lack of secondary wall formation in xylem and cortical sclerenchyma. These data indicate that growth of deepwater-rice internoes involves a balance between elongation and differentiation of the stem. Submergence shifts this balance in favor of growth. PMID- 24232756 TI - The effect of submergence, ethylene and gibberellin on polyamines and their biosynthetic enzymes in deepwater-rice internodes. AB - Submergence and treatment with ethylene or gibberellic acid (GA3) stimulates rapid growth in internodes of deepwater rice (Oryza sativa L. cv. "Habiganj Aman II"). This growth is based on greatly enhanced rate of cell-division activity in the intercalary meristem (IM) and on increased cell elongation. We chose polyamine biosynthesis as a biochemical marker for cell-division activity in the IM of rice stems. Upon submergence of the plant, the activity of S adenosylmethionine decarboxylase (SAMDC; EC 4.1.1.50) in the IM increased six- to tenfold within 8 h; thereafter, SAMDC activity declined. Arginine decarboxylase (ADC; EC 4.1.1.19) showed a similar but less pronounced increase in activity. The activity of ornithine decarboxylase (ODC; EC 4.1.1.17) in the IM was not affected by submergence. The levels of putrescine and spermidine also rose in the IM of submerged, whole plants while the concentration of spermine remained low. The increase in SAMDC activity was localized in the IM while the activity of ADC rose both in the node and the IM above it. The node also contained low levels of ODC activity which increased slightly following submergence. Increased activities of polyamine-synthesizing enzymes in the nodal region of submerged plants probably resulted from the promotion of adventitious root formation in the node. Treatment of excised rice-stem sections with ethylene or GA3 enhanced the activities of SAMDC and ADC in the IM and inhibited the decline in the levels of putrescine and spermidine. We conclude that SAMDC and perhaps also ADC may serve as biochemical markers for the enhancement of cell-division activity in the IM of deepwater rice. PMID- 24232757 TI - Characterization and properties of the spinach chloroplast transcriptionally active chromosome isolated at high ionic strength. AB - The transcriptionally active chromosome (TAC) of spinach (Spinacia oleracea L.) chloroplasts has been isolated at a high ionic strength, with low mechanical shearing, by glycerol gradient centrifugation. The properties of the TAC differ from those previously reported for the TAC isolated either from Euglena chloroplasts or from spinach using a low-ionic-strength solubilization medium and gel filtration. The high-salt-isolated TAC is homogenous in density but not in size and contains fewer weakly bound proteins than its lowsalt-isolated homologue. In vitro, it promotes elongation of the RNA chains previously initiated in vivo. Transcription is not limited to the ribosomal DNA. The transcriptional pattern is not strongly affected by the high-salt preparation. Ribonuclease pretreatment of the TAC, prior to the in-vitro transcription, leads to a more than tenfold increase of the transcription activity. These properties are discussed in relation to the structure of the spinach chloroplast chromosome. PMID- 24232758 TI - Microaerobiosis is not involved in the induction of pea nodulin-gene expression. AB - Gene expression in pea roots grown in a medium with a low oxygen concentration was compared with that in nitrogen-fixing pea root nodules induced by Rhizobium bacteria. The results show that during microaerobiosis the expression of eight genes is increased. None of these belong to the group of genes earlier identified as nodulin genes. On the other hand, no enhanced transcription of microaerobic genes can be detected during nodule development and hybridizations of Northern blots, containing nodule RNA and RNA isolated from oxygen-stressed roots, show that the alcohol dehydrogenase genes are not expressed at a higher level in pea root nodules whereas a higher expression is observed during microaerobiosis. From these observations it can be concluded that it is unlikely that a low concentration of free oxygen induces the expression of nodulin genes. Furthermore, genes that are activated as a result of oxygen deficiency are not expressed in pea root nodules, indicating that if the concentration of free oxygen is low the nodule cells do not suffer under microaerobic conditions. Probably, leghemoglobin functions as an efficient oxygen buffer for the energy generating process in both the plant cells and the bacteroids. PMID- 24232759 TI - Utilization of sulfonic acids as the only sulfur source for growth of photosynthetic organisms. AB - Growth on ethanesulfonic acid as the only sulfur source was found to occur in ten of the 14 green algae tested and in three of the ten cyanobacteria analyzed. Similar growth could not be demonstrated in the higher plant Lemna minor, or in tissue cultures of anise, sunflower and tobacco.Organisms growing on sulfonic acids as the only sulfur source developed an uptake system for ethanesulfonate found neither in algae growing on sulfate nor in algae unable to utilize sulfonic acids for growth. The development of sulfonate transport was not caused by substrate induction, but by conditions of sulfate starvation. The presence of this uptake system was always correlated with an increased sulfate-uptake capacity. Enhanced sulfate uptake was found in all S-deficient and sulfonate grown cultures tested, indicating sulfate limitation as the regulatory signal. A lag period of 2-2.5 h after transfer to sulfate deprivation was needed for expression of both enhanced sulfate uptake and ethanesulfonate uptake in case of the green alga Chlorella fusca.It is speculated that the availability of sulfate (pool size) or a metabolic product in equilibrium with oxidized sulfur compounds (sulfate ester? sulfolipids?) controls sulfate and sulfonate uptake systems. The principle of (coordinated) derepression by starvation is discussed as a general strategy in photosynthetic organisms. PMID- 24232760 TI - The loss of carbon-20 in C19-gibberellin biosynthesis in a cell-free system from Pisum sativum L. AB - The fate of the carbon-20 atom in gibberellin (GA) biosynthesis was studied in a cell-free system from Pisum sativum. This carbon atom is lost at the aldehyde stage of oxidation when C20-GAs are converted to C19-GAs. Gibberellin A12 labeled with (14)C at C-20 was prepared from [3'-(14)C]mevalonic acid with a cell-free system from Cucurbita maxima and incubated with the pea system. Analysis of the gas and aqueous phases showed that (14)CO2 was formed at the same rate and in nearly equivalent amounts as (14)C-labeled C19-GAs whereas [(14)C]formic acid and [(14)C]formaldehyde were not detectable. The possibility that C-20 had been lost as formic acid which had then been converted to CO2 was investigated by control incubations with [(14)C]formic acid. The rate of release of (14)CO2 from [(14)C]formic acid was only one fiftieth of the rate of (14)CO2 release from [(14)C]GA12 as the substrate. We conclude that in the formation of C19-GAs from C20-GAs, the C-20 is removed directly as CO2. PMID- 24232761 TI - Are sucrosyl-oligosaccharides synthesized in mesophyll protoplasts of mature leaves of Cucumis melo? AB - Biosynthesis of sucrosyl-oligosaccharides (raffinose, stachyose) was traced in source leaves of Cucumis melo after (14)C-photoassimilation. The main carbon compound exported was (14)C-labeled stachyose. No oligosaccharide synthesis was detected in young, importing leaves. Mesophyll protoplasts, isolated from mature leaves which had previously photosynthesized (14)CO2, did not contain (14)C oligosaccharides but contained [(14)C]-sucrose and (14)C-hexoses. Isolated minor vein-enriched fractions from the same leaves, however, showed nearly 30% of the (14)C of the neutral fraction to be in oligosaccharides. Isolated, viable mesophyll protoplasts incubated with NaH(14)CO3 also failed to incorporate radioactivity into oligosaccharides, although sucrose and galactinol synthesis was unimpaired. Galactinolsynthase activity in leaf extracts and in mesophyll protoplasts was 16.8 MUmol.h(-1).mg(-1) protein and 13.8 MUmol.h(-1).mg(-1) protein, respectively. Galactosyltransferase (EC 2.4.1.67), which synthesizes stachyose from raffinose and galactinol, had an activity of 50 nmol.h(-1).mg(-1) protein in leaf extracts and was also present in the minor-vein-enriched fraction, but could not be detected in mesophyll protoplast lysates. The results indicate that mesophyll cells may not be the site of stachyose synthesis although precursor compounds like sucrose and galactinol are synthesized there. PMID- 24232762 TI - Effects of abscisic acid on photosynthesis in whole leaves: changes in CO2 assimilation, levels of carbon-reduction-cycle intermediates, and activity of ribulose-1,5-bisphosphate carboxylase. AB - Addition of abscisic acid (ABA) to the transpiration stream of leaves of Xanthium strumarium caused stomatal closure and, simultaneously, an independent reduction of CO2 assimilation. An attempt was made to identify the site of inhibition that had occurred, presumably, in the path of photosynthetic carbon reduction. Leaves were supplied with ABA. When inhibition of photosynthesis was fully expressed, the partial pressure of CO2 in the intercellular spaces was adjusted to the level that had occurred before ABA had been applied and before stomata had closed. Then the leaf was rapidly frozen, and pool sizes of carbon-reduction-cycle intermediates were determined. Comparison with samples from control leaves showed that the decline in the rate of assimilation was associated with decreases of the levels of 3-phosphoglycerate, triose phosphates, fructose-1,6-bisphosphate, and hexose phosphates. In contrast, the pool size ofribulose-1,5-bisphosphate (RuBP) remained unchanged or even increased. Similar results were obtained with leaves of Zea mays, in which the levels of all measured intermediates, including malate and pyruvate, declined after application of ABA; the level of RuBP rose. In other experiments with leaves of X. strumarium, rates of CO2 assimilation were lowered by reductions in the partial pressure of CO2 in the ambient air. Relationships between assimilation rates of CO2 and metabolite levels were similar to those determined after applications of ABA at constant partial pressure of CO2. Because the uptake of CO2 decreased in ABA-treated leaves in spite of continued availability of CO2 and RuBP, we concluded that application of ABA caused an inhibition of the carboxylation of RuBP in both, the C3 species, X. strumarium, and the C4 species, Z. mays. However, the RuBP-carboxylase activity of rapidly prepared extracts of ABA-treated leaves was as high as that of control leaves. The substance or the process which, after application of ABA, interferes with the carboxylation of RuBP remains unknown. PMID- 24232763 TI - Tetracyclines, verapamil and nifedipine induce callose deposition at specific cell sites in Riella helicophylla. AB - The Ca(2+) indicator 7-chlorotetracycline has been shown to bind to a pore complex on both outer surfaces of all non-meristematic cells in the unistratose thallus of Riella ('chlorotetracycline-binding surface region'=CSR; Grotha, 1983, Planta 158, 473-481). Prolonged treatment of the thallus with 7 chlorotetracycline, 5-hydroxytetracycline, verapamil and desmethoxyverapamil induces the deposition of callose at the same region. The influence of various treatments on verapamil-induced CSR-callose was measured in situ by microfluorometry of aniline-blue-stained material. Callose deposition is maximal at 10(-4)M verapamil or 5.10(-5)M desmethoxyverapamil with 2.10(-4)M Ca(2+) or Mg(2+) in the medium. The reaction is completely inhibited at pH 5.5 and is optimal between pH 6.5 and 7.5. The production of CSR-callose is absolutely light dependent with callose being first visible after 30 min of light. La(3+), ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid and amiprophosmethyl, antagonists of Ca(2+) functions, and 2-deoxy-D-glucose suppress the verapamil induction of CSR-callose. Furthermore the ionophores A 23187, valinomycin and monensin effectively block the reaction. The deposition of CSR callose is diminished at increasing external osmolarity and is abolished at osmotic values that stimulate plasmolysis-callose. Wounding causes the formation of wound-callose but inhibits the induction of CSR-callose in cells of the wound edge. Nifedipine increases or prolongs callose synthesis in cell plates. The Ca(2+)-channel blocker diltiazem is completely ineffective. It is suggested as a working hypothesis that verapamil-induced CSR-callose synthesis is caused by a local change in membrane permeability, possibly as a consequence of the opening of Ca(2+) channels being involved in Golgi-vesicle mediated exocytosis (A. Kramer and H. Lehmann, 1986, Ber. Dtsch. Bot. Ges. 99, 111-121). PMID- 24232764 TI - Sequence homologies between glyoxysomal and mitochondrial malate dehydrogenase. AB - The comparison of mitochondrial and glyoxysomal malate dehydrogenase (EC 1.1.1.37) from cotyledons of germinating watermelon (Citrullus vulgaris Schrad., cv. Kleckey's Sweet No. 6) by means of serological methods and peptide patterns revealed a high degree of homology. The N-terminal sequence analysis yielded a distinct presequence of eight or nine amino-acid residues, respectively, which is followed by an almost identical stretch of at least 20 amino-acid residues. A very similar domain has been recognized for mitochondrial malate dehydrogenase from porcine heart and yeast, and for Escherichia coli malate dehydrogenase. PMID- 24232765 TI - Uridine 5'-diphosphate-xylose: anthocyanidin 3-O-glucose-xylosyltransferase from petals of Matthiola incana R.Br. AB - Petals of genetically defined lines of Matthiola incana R.Br. contain a glycosyltransferase which catalyzes the transfer of the xylosyl moiety of uridine 5'-diphosphate-xylose to the glucose of cyanidin 3-glucoside. The enzyme also uses 3-glucosides of pelargonidin and delphinidin, cyanidin 3-(p-coumaroyl) glucoside and 3-(caffeoyl)-glucoside as substrates. The xylosyltransferase exhibits a pH optimum of 6.5. The enzyme activity depends on the stage of bud and flower development. Accumulation of cyanidin 3-glucoside during flower development is correlated with xylosyltransferase activity. PMID- 24232766 TI - Glucomannan-synthase activity in differentiating cells of Pinus sylvestris L. AB - Particulate membrane preparations have been isolated from cambial cells, and from differentiating and differentiated xylem cells of the main stem of pine trees. These preparations synthesise a beta1->4 glucomannan from guanosine 5' diphosphate-mannose. The polysaccharide and the synthase have been characterized and the Km and Vmax for the synthase determined as 85 MUM and 52.9 MUM.min(-1), respectively. The enzymic activity was inhibited by the addition of guanosine 5' diphosphate-D-glucose so that the presence of an epimerase on the particulate fraction in conjunction with the synthase probably allowed the heteropolymer to be formed with the optimal ratio of the concentrations of the nucleoside diphosphate sugar donors. No evidence for a polyprenyl-phosphate derivative as an intermediate during the polymer synthesis was obtained. Part of the control mechanism for the deposition of the large amounts of the glucomannan during the secondary thickening of the tracheids of the vascular system is by an increase in the amount of synthase activity at the endomembrane system of the cells. This probably occurs by an increase in the amount of enzyme which is modulated by gene regulation during differentiation. PMID- 24232767 TI - Differences in amino acid sequence of the large subunit of ribulose-1,5 bisphosphate carboxylase/oxygenase from two species of Dasycladaceae. AB - In contrast to other plants the plastid genome of Acetabularia is larger in size and shows a high degree of variability. This study on the chloroplast-encoded large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase demonstrates that strongly conserved areas also exist in the plastid genome of the Dasycladaceae. Searching for differences in the amino acid sequence of the large subunit from Acetabularia mediterranea and Acicularia schenckii, proteolytic peptides which differ in their elution behaviour in reverse-phase high performance liquid chromatography were sequenced. Only six amino acids were found to be exchanged in the large subunit from these two species. Since these two species diverged approx. 150 million years ago, these results imply that 0.84 amino-acid exchanges per 100 amino acids have occurred in 10(8) years, underlining the strong conservatism of the large subunit. PMID- 24232768 TI - A new lectin from tulip (Tulipa) bulbs. AB - A lectin was isolated from tulip (Tulipa) bulbs by affinity chromatography on fetuin-agarose and partially characterized. The tulip lectin is a tetrameric protein composed of four identical subunits of Mr 28 000, which are not held together by disulphide bonds. It is not glycosylated and has an amino-acid composition typified by a high content of asparagine-aspartic acid, leucine, glycine and serine. Tulip lectin agglutinates human red blood cells, but has a much higher specific activity with rabbit erythrocytes. In hapten-inhibition assays with the latter type of red blood cell the lectin exhibits a complex specificity, whereas its agglutination with human erythrocytes is readily inhibited by N-acetylgalactosamine, lactose, fucose and galactose. PMID- 24232769 TI - Induction of nitrate reductase by cytokinin and ethylene in Agrostemma githago L. embryos. AB - In dark-grown, isolated embryos of Agrostemma githago, a transient period of nitrate-reductase (NR) (NADH: nitrate oxidoreductase, EC 1.6.6.1) activity occurred from 6 to 36 h after the start of imbibition. During this period, NR activity was enhanced by nitrate, 6-benzylamino-purine and ethylene. Ethylene and 6-benzylamino-purine acted synergistically, whereas ethylene had no effect on nitrate induction. Aminoethoxyvinyl-glycine, an inhibitor of ethylene biosynthesis, inhibited the cytokinin-induced increase of NR activity, but had no effect on the nitrate-induced increase. The inhibition by aminoethoxyvinylglycine was overcome completely by ethylene. The ethylene precursor 1-aminocyclopropane-1 carboxylic acid had the same effect on NR activity as ethylene. Our data indicate that NR induction by cytokinins only occurs in the presence of ethylene, and that nitrate enhances NR activity through a mechanism which is distinct from the induction by hormones. PMID- 24232770 TI - Effect of ammonium and nitrate on growth and appearance of nitrate reductase and nitrite reductase in dark- and light-grown mustard seedlings. AB - Nitrate-induced and phytochrome-modulated appearance of nitrate reductase (NR; EC 1.6.6.1) and nitrite reductase (NIR; EC 1.7.7.1) in the cotyledons of the mustard (Sinapis alba L.) seedling is strongly affected by externally supplied ammonium (NH 4 (+) ). In short-term experiments between 60 and 78 h after sowing it was found that in darkness NH 4 (+) -simultaneously given with NO 3 (-) -strongly inhibits appearance of nitrate-inducible NR and NIR whereas in continuous far-red light-which operates exclusively via phytochrome without significant chlorophyll formation -NH 4 (+) (simultaneously given with NO 3 (-) ) strongly stimulates appearance of NR. The NIR levels are not affected. This indicates that NR and NIR levels are regulated differently. In the absence of external NO 3 (-) appearance of NR is induced by NH4 in darkness as well as in continuous far-red light whereas NIR levels are not affected. On the other hand, in the absence of external NO 3 (-) , exogenous NH 4 (+) strongly inhibits growth of the mustard seedling in darkness as well as in continuous far-red light. This effect can be abolished by simultaneously supplying NO 3 (-) . The adverse effect of NH 4 (+) on growth ('NH 4 (+) -toxicity') cannot be attributed to pH-changes in the medium since it was shown that neither the growth responses nor the changes of the enzyme levels are related to pH changes in the medium. Non-specific osmotic effects are not involved either. PMID- 24232771 TI - Importance of the cap in maize root growth. AB - A large population of primary roots of Zea mays (cv. LG 11) was selected for uniform length at zero time. Their individual growth rates were measured over an 8-h period in the vertical position (in humid air, darkness). Three groups of these roots with significantly different growth rates were then chosen and their cap length was measured. It was found that slowly growing roots had long caps whereas rapidly growing roots had short caps. The production by the cap cells of basipetally transported growth inhibitors was tested (biologically by the curvature of half-decapped roots) and found to be significantly higher for longer root caps than that for shorter ones. PMID- 24232772 TI - Erratum. PMID- 24232773 TI - No association between vitamin D intake and incident psoriasis among US women. AB - We investigated the association between dietary, supplementary and total vitamin D intake and incident psoriasis in women. A prospective study was performed of 70,437 US female nurses aged 47-74 enrolled in the Nurses' Health Study who did not have psoriasis at baseline in 1994 and who completed semi-quantitative food frequency questionnaires in 1994, 1998, 2002 and 2006. The incidence of clinician diagnosed psoriasis was ascertained and validated by self-reported questionnaires. 502 confirmed incident psoriasis cases were documented during 973,057 person-years of follow-up from 1994 June to 2008 June. Association between vitamin D intake and incident psoriasis was assessed using multivariable adjusted cox regression analysis. After adjusting for age, smoking, body mass index, calorie intake, UV flux, exercise and alcohol use, there was no significant association between vitamin D intake (dietary, supplementary and total vitamin D) and the risk of incident psoriasis. Compared with women whose dietary vitamin D intake was <100 IU/day, multivariate relative risks for psoriasis was 1.13 (95 % CI 0.66-1.92) for >=400 IU/day (P trend = 0.88). The multivariate relative risk for women who took supplementary vitamin D >=400 IU/day was 1.18 (95 % CI 0.88-1.58) compared with women who did not take supplementary vitamin D. The multivariate risk for women who had total vitamin D intake of 300-399 IU/day was no different than at higher and lower doses of vitamin D intake. Our study does not support preventive roles of dietary or supplemental vitamin D intake for incident psoriasis. PMID- 24232774 TI - Nutritional and hormonal requirements of Ginkgo biloba embryo-derived callus and suspension cell culture. AB - Calli were obtained from Ginkgo biloba embryos grown on Murashige and Skoog (MS) medium. The G. biloba cells could grow on either MS or Gamborg B5 mineral salt medium supplemented with sucrose (3% and 2%, respectively) and naphthaleneacetic acid (NAA) and kinetin (K) in concentrations ranging from 0.1 to 2.0 mg.L(-1). Best growth and maintenance of callus cultures were achieved using MS medium supplemented with 2 mg.L(-1) NAA and 1 mg.L(-1) K (N2K1MS). Light was required to maintain healthy growth of the callus tissue.In both MS and B5 based media, sucrose was hydrolyzed extracellularly before being taken up by Ginkgo cell suspension cultures. Specific growth rates of 0.13 d(-1) and 0.08 d(-1) were obtained in MS medium supplemented with 1 mg.L(-1) NAA, 0.1 mg.L(-1) K and 30 g.L(-1) sucrose (N1K0.1MS) and B5 medium supplemented with the same growth regulator regime and 20 g.L(-1) sucrose (N1K0.1B5) respectively. Complete phosphate and ammonium uptake was observed in 11 days when cultured in MS medium and 10 days and 4 days respectively when cultured in B5 medium. During the culture, G. biloba cells consumed only 64% and 29% of the nitrate content of N1K0.1MS and N1K0.1B5 media respectively. Maximum dry biomass concentrations were 13.4 g.L(-1) and 7.9 g.L(-1), and yields on carbohydrate were 0.39 and 0.45 in N1K0.1MS and N1K0.1B5 media respectively. The better performance of MS cultures came from the higher sucrose and nitrogen salts concentrations of this medium. PMID- 24232775 TI - A novel approach for efficient plant regeneration from long-term suspension culture of wheat. AB - Hexaploid wheat plants were easily regenerated from young embryo-derived callus for twelve genotypes tested. After a 2.5 years culture period, however, most of the callus cells lost their ability to regenerate into shoots, but not into roots.A novel approach was used to regenerate shoots from the long-term suspension cultured cells. In general, instead of selecting embryogenic callus as source material, this approach requires the inoculation of unselected callus into liquid medium followed by removing the free floating cell portion, selecting out non-root forming cell clumps from the root forming primary suspension culture, and growing the putative shoot-competent clumps in liquid medium with reduced auxin concentrations. We have successfully established shoot-competent wheat suspension cultures for cv. 'Mustang'. High (>80%) frequencies of plant regeneration were observed from plating of 2.5 year suspension cultures. The suspension cultures established by this approach have been utilized to select for heat tolerant variants and will be an ideal source material for protoplast culture and transformation studies. This approach can also be applied to other cereal crops which form roots easily but are unstable in maintaining long term regenerable cultures and which are not easily adaptable to suspension culture. PMID- 24232776 TI - In vitro study of transgenic tobacco expressing Arabidopsis wild type and mutant acetohydroxyacid synthase genes. AB - Genes coding for the enzyme acetohydroxyacid synthase, often referred to as acetolactate synthase (AHAS, ALS; EC 4.1.3.18), from wild type Arabidopsis thaliana and a sulfonylurea-resistant mutant line GH50 (csrl-1; Haughn et al. 1988) were introduced in Nicotiana tabacum. Both genes were expressed at high levels with the 35S promoter. The csrl-1 gene conferred high levels of resistance to chlorsulfuron whereas the wild type gene did not. As selectable markers, chimaeric AHAS genes yielded transgenic plants on chlorsulfuron but at much lower efficiencies than with a chimaeric neomycin phosphotransferase gene on kanamycin (Sanders et al. 1987). Shoot differentiation from leaf discs was delayed on chlorsulfuron by 4-6 weeks. This study indicated a role for mutant AHAS genes in the genetic manipulation of herbicide resistance in transgenic plants but as selectable markers for plant cells undergoing differentiation no advantage over other genes was perceived. PMID- 24232777 TI - Salt tolerant sugarbeet progeny from tissue cultures challenged with multiple salts. AB - Lines of sugarbeet (Beta vulgaris L.) tolerant of multiple salts was accomplished by an in vitro multiple salt challenge. Petioles were placed on RV medium amended with 5 different salts along with Murashige and Skoog base salts for one month. Surviving shoots were cultured on RV medium to obtain petioles for subsequent challenges. During the first, second and third challenges, organogenically regenerated shoots developed from 5%, 46%, and 80% of the petioles, respectively. After the third multiple salt challenge, tolerant shoots were rooted and transplanted in soil. Salt was added to this soil at 1.0% by weight and plants were observed for 2 months. The ten most salt tolerant plants were vernalized to obtain seed. The R1 seed and controls were planted in soil containing 0%, 0.61% or 0.77% multiple salts per dry soil weight. Emergence of R1 seedlings was significantly greater than the controls under salt stress. Multiple salt tolerant R1 plants were maintained in salt amended soil to the 8-10 leaf stage and appeared as healthy and vigorous as the control growing in salt free soil. PMID- 24232778 TI - Biotransformation of 5betaH-pregnan-3betaol-20-one and cardenolides in cell suspension cultures of Nerium oleander L. AB - In order to demonstrate enzyme activities playing a role in the biosynthesis of cardenolides and 2,6-dideoxysugars, 5betaH-pregnan-3betaol-20-one and cardenolides (digitoxigenin, oleandrigenin/L-oleandrose, oleandrin, neriifolin, digitoxigeninmonodigitoxoside and strospeside) were fed to cell suspension cultures of Nerium oleander L.. It could be shown that cell suspension cultures of Nerium oleander L. are able to oxidize, isomerize and glucosylate 5betaH steroidaglycones at C-3. The respective glucosides of the 5betaH-steroid aglycones are the main biotransformation products. These cell cultures are an appropriate tool for the production of labelled 5betaH-steroidglucosides. PMID- 24232779 TI - Somatic hybrid plants from sexually incompatible woody species: Citrus reticulata and Citropsis gilletiana. AB - Allotetraploid intergeneric somatic hybrid plants between Citrus reticulata Blanco cv. Cleopatra mandarin and Citropsis gilletiana Swing. & M. Kell. (common name Gillet's cherry orange) were regenerated following protoplast fusion. Cleopatra protoplasts were isolated from an ovule-derived embryogenic suspension culture and fused chemically with leaf-derived protoplasts of Citropsis gilletiana. Cleopatra mandarin and somatic hybrid plants were regenerated via somatic embryogenesis. Hybrid plant identification was based on differential leaf morphology, root-tip cell chromosome number, and electrophoretic analyses of phosphoglucose mutase (PGM) and phosphohexose isomerase (PHI) isozyme banding patterns. This is the first somatic hybrid within the Rutaceae reported that does not have Citrus sinensis (sweet orange) as a parent, and the first produced with a commercially important citrus rootstock and a complementary but sexually incompatible, related species. PMID- 24232780 TI - Genetic transformation of Medicago species by Agrobacterium tumefaciens and electroporation of protoplasts. AB - Shoot and leaf segments of a non-regenerable Medicago sativa L. genotype were cocultivated with the "shooty" mutant of Agrobacterium tumefaciens carrying the pGV 2206 plasmid. Transformed callus lines were selected and regenerated on the hormone free B5 medium. Southern blot analysis demonstrated integration of T-DNA in to the genome of the regenerated plants.Transgenic plants resistant to kanamycin were obtained by electroporation of Medicago borealis protoplasts with the pGA 472 plasmid DNA. PMID- 24232781 TI - Phytochrome-mediated responses of cells and protoplasts of green calli obtained from the leaves of a CAM plant. AB - Green callus obtained from leaves of the CAM-inducible plant Kalanchoe blossfeldiana cv. Montezuma has previously been shown to perform C3-type photosynthesis under 16-h days and to shift to crassulacean acid metabolism (CAM) under 9-h days. The utilization of photoperiodic regimes (i.e. night interruptions by 30 min red light) established that CAM induction in the callus was under the control of phytochrome, as shown by measurements of CAM criteria: phosphoenolpyruvate carboxylase activity and malic acid pools. Short-term responsiveness of the callus cells to phytochrome modulations by monochromatic radiations was also established by the rapid changes observed in the diameter of the callus-derived protoplasts. These results provide further evidence that whole plant correlations are not necessary for phytochrome operativity. PMID- 24232782 TI - Passage of lanthanum through the pollen grain wall of Olea europaea L. during development. AB - In order to study the behavior of the exine as a site of passage of material from the locule of the anther, lanthanum nitrate was used to locate the possible routes of communication between the Olea europaea L. pollen grain and its external environment from the period of exine consolidation until dehiscence of the anther. In all four stages of development studied, dense lanthanum deposits occupied microchannel-like orifices, whereas these dense deposits occupied the apertural regions only in the first stages of development. Lanthanum precipitate is also present in the endexine, intine and cytoplasmic vesicles of mature pollen. The transportational function of the apertures is discussed in relation to the presence of dense lanthanum deposits in some stages of pollen grain. PMID- 24232783 TI - Chromosome number and DNA content of tobacco cells adapted to NaCl. AB - Cultured tobacco (Nicotiana tabacum L. cv. Wisconsin 38) cells were found to have altered DNA contents and chromosome numbers after adaptation to NaCl. Cells adapted to 428 mM NaCl were predominately hexaploid compared to the normal tetraploid 2N(2C)=4X=48 chromosome number of unadapted cells. Enrichment of the cell population for hexaploid cells occurred only after exposure to higher NaCl (428 mM), not lower levels of NaCl (171 mM). The majority of adapted cells remain hexaploid for at least 25 cell generations after removal from NaCl exposure. Adapted cell populations were found to have fewer cells with highly polyploid (2N>=96) nuclei. Salt tolerance of hexaploid cells was not found to be significantly greater than that of tetraploid cells. Cells with higher ploidy levels were less salt tolerant. It is suggested that high levels of NaCl induce polyploidization and that exposure to NaCl selects against cells with very high ploidy levels. PMID- 24232784 TI - Chromosome number and nuclear DNA content of plants regenerated from salt adapted plant cells. AB - Plants regenerated from tobacco (Nicotiana tabacum L. cv. Wisconsin 38) cells that were adapted to 428 mM NaCl were found to have hexaploid or near-hexaploid chromosome numbers compared to the normal tetraploid, 2N(2C)=4X=48 chromosome numbers of plants regenerated from unadapted cells. Even though cells with chromosome numbers other than hexaploid were found in the cell population only hexaploid plants were regenerated. The hexaploid condition may impart some karyotypic stability that allows more efficient morphogenic activity. The hexaploid condition could not be correlated with several phenotypic alterations associated with plants regenerated from adapted cells, including male sterility and increased salt tolerance. PMID- 24232785 TI - Agrobacterium - and microprojectile - mediated viral DNA delivery into barley microspore-derived cultures. AB - Anther cultures of barley (Hordeum vulgare L. var. "Igri") were used as targets for Agrobacterium-mediated DNA transfer and direct DNA uptake by particle bombardment. A wheat dwarf virus construct which can replicate to a high copy number in cereal cells provided a sensitive marker for successful DNA delivery. Although DNA delivery was achieved using both procedures, particle bombardment gave more reproducible and higher levels of infection. The ability to deliver DNA into cereal cells which have a high regeneration capacity may provide a route for stable transformation. PMID- 24232786 TI - Direct assessment of hormone stimulated transcription in protoplasts and isolated nuclei of Petunia hybrida. AB - We have developed a simplified procedure for the detection of cellular RNA transcripts. Entire protoplasts, isolated nuclei or nuclei sorted according to cell cycle phases are directly dotted onto filters and hybridized. Transcripts are quantified thereupon without any RNA extraction methodology. Previously, auxin and cytokinin have been shown to increase the level of RNA in Petunia mesophyll protoplasts after 18h of culture. The present results show that auxin and cytokinin also increase the level of ATPase and rDNA gene transcripts in protoplast released nuclei. For the ribosomal gene, however, transcripts increase in protoplasts with time in absence of exogenous hormones. PMID- 24232787 TI - Determination of physical membrane properties of plant cell protoplasts via the electrofusion technique: prediction of optimal fusion yields and protoplast viability. AB - By variation of physical parameters (field strength, pulse duration) which result in electrofusion and electroporation, properties of the plasma membrane of different types of plant cell protoplasts were analyzed. The lower threshold for that field pulse intensity at which membrane breakdown occurred (recorded as fusion event) depended on pulse duration, protoplast size, and protoplast type (tobacco, oat; vacuolated, evacuolated). This fusion characteristic of plant protoplasts can also be taken as a measure of the charging process of the membrane and allows thus a non-invasive determination of the time constant and the specific membrane capacitance. Although the fusion yield was comparable at pulse duration/field strength couples of, e.g., 10 MUs/1.5 kV*cm(-1) and 200 MUs/0.5 kV*cm(-1), hybrid viability was not. Rates of cell wall regeneration and cell division of tobacco mesophyll protoplasts were not affected but may have been increased at short pulse duration/high field strength. Plating efficiency, in contrast, was significantly decreased with longer pulse duration at low field strengths. PMID- 24232789 TI - Erratum. PMID- 24232788 TI - A protoplast-to-plant system in chrysanthemum: differential responses among several commercial clones. AB - Plant regeneration has been obtained from Chrysanthemum mesophyll protoplasts. Of the twenty-nine clones studied, division was observed for eighteen clones, and coupled with colony formation for sixteen of them. Elimination of NH4NO3 from the culture medium greatly improved colony survival in culture. Calli were obtained from colonies of five clones, and for clone n(o) 42 buds were produced. Regeneration ability, for such protoplast-derived calli of clone n(o) 42, was retained over a prolonged culture period. The regenerated plants were successfully transferred to the glasshouse (4 to 5 months from protoplast isolation). PMID- 24232790 TI - In vitro morphogenesis of arrested embryos from lethal mutants of Arabidopsis thaliana. AB - Arrested embryos from lethal (emb) mutants of Arabidopsis thaliana were rescued on a nutrient medium designed to promote plant regeneration from immature wild type cotyledons. The best response was observed with mutant embryos arrested at the heart to cotyledon stages of development. Embryos arrested at a globular stage produced callus but failed to turn green or form normal shoots in culture. Many of the mutant plants produced in culture were unusually pale with abnormal leaves, rosettes, and patterns of reproductive development. Other plants were phenotypically normal except for the presence of siliques containing 100% aborted seeds following self-pollination. These results demonstrate that genes with essential functions during plant embryo development differ in their pattern of expression at later stages of the life cycle. Most of the 15 genes examined in this study were essential for embryogenesis but were required again for subsequent stages of development. Only EMB24 appeared to be limited in function to embryo development. These differences in the response of mutant embryos in culture may facilitate the classification of embryonic lethals and the identification of genes with developmental rather than housekeeping functions. PMID- 24232791 TI - Small mitochondrial DNA molecules of wild abortive cytoplasm in rice are not necessarily associated with CMS. AB - Mitochondrial DNA was isolated from leaf tissue of both the cytoplasmic male sterile line of Indica rice variety V41, which carries wild abortive (WA) cytoplasm, and from the corresponding maintainer line. In addition to the main mitochondrial DNA, four small plasmid-like DNA molecules were detected in both the male sterile and fertile lines. Restriction analysis of total mitochondrial DNA from the male sterile and fertile lines showed DNA fragments unique to each. Our findings suggest that the four small mitochondrial DNA (mtDNA) molecules are conserved when WA cytoplasm is transferred into different nuclear backgrounds. However, there is no simple correlation between the presence/ absence of small mitochondrial DNA molecules and the expression of WA cytoplasmic male sterility (CMS). PMID- 24232792 TI - A specific rearrangement of mitochondrial DNA induced by tissue culture. AB - The induction, growth and regeneration of sugar beet callus to whole plants were all found to be highly genotype-specific. Regenerants of one line (of sterile cytoplasm) were obtained and a study of the chloroplast and mitochondrial DNA in these somaclones was undertaken by gel electrophoresis and cosmid hybridization. In one somaclone a rearrangement in the mitochondrial genome was observed; the novel arrangement of this part of the genome was identical to the corresponding area of the genome of the normal cytoplasm though it was otherwise of sterile type. This suggests that mitochondrial DNA may have a propensity to undergo certain types of rearrangement. PMID- 24232793 TI - A contiguous sequence in spinach nuclear DNA is homologous to three separated sequences in chloroplast DNA. AB - A 3.4-kbp nuclear (n) DNA sequence has greater than 99% sequence homology to three segments of the chloroplast (cp) genes rps2, psbD/C, and psaA respectively. Each of these cpDNA segments is less than 3 kbp in length and appears to be integrated, at least in part, into several (>5) different sites flanked by unique sequences in the nuclear genome. Some of these sites contain longer homologies to the particular genes, while others are only homologous to smaller parts of the cp genes. Both the cpDNA fragments found in the nuclear genome and their flanking nDNA sequences are invested with short repeated A-T rich sequences but, apart from a hexanucleotide sequence and a palindromic sequence identified near each recombination point, there is no obvious structure that can suggest a mechanism of DNA transfer from the chloroplast to the nucleus in spinach. PMID- 24232794 TI - Enzyme diversity in pearl millet (Pennisetum glaucum) : 2. Africa and India. AB - The survey of enzyme polymorphism in West African pearl millet cultivars reported by Tostain et al. 1987 has been extended to include populations from other regions of Africa and from India. The eight enzyme systems studied included: alcohol dehydrogenase, beta-esterase, catalase, phosphoglucoisomerase, phosphoglucomutase, 6-phosphogluconate dehydrogenase, glutamate oxaloacetate transaminase, and malate dehydrogenase. One-hundred-ninety-nine populations of millet were analyzed, including 74 populations studied earlier. No new enzyme diversity was observed. Intrapopulation diversity ranged from 70%-90% of the total diversity, depending on their regions of origin. Four principal groups were distinguished in the following decreasing order of diversity: early-maturing cultivars from West and East Africa, late - maturing cultivars from West and East Africa, cultivars from India, and cultivars from southern Africa. The early maturing cultivars were distributed between two principal focal points from East Africa in the East to Mali in the West. In the center were found millets from Niger which were most diverse. Indian and southern African cultivars were distinct, with the former appearing relatively similar to those of Niger, and the latter somewhat similar to late-maturing cultivars from West Africa, a diverse group that included late-maturing cultivars from East Africa. Based on the results obtained, an evolutionary hypothesis proposed here includes: multiple domestications in the Sahel, creation of early-maturing cultivars and their migration eastwards to India plus a southwards migration to Sudanian zone, and creation of late-maturing cultivars and their migration simultaneously westwards, eastwards, and southwards to southern Africa. PMID- 24232795 TI - Analysis of chloroplast and mitochondrial DNAs in asymmetric somatic hybrids between tobacco and carrot. AB - Chloroplast and mitochondrial DNAs have been examined by comparison of restriction enzyme patterns in asymmetric hybrid plants, resulting from the fusion between leaf mesophyll protoplasts of Nicotiana tabacum (Solanaceae), and irradiated cell culture protoplasts of Daucus carota (Umbellifereae). These somatic hybrids with normal tobacco morphology were selected as a consequence of the transfer of methotrexate and 5-methyltryptophan resistance from carrot to tobacco. The restriction patterns of chloroplast DNAs in somatic hybrids were indistinguishable from the tobacco parent. However, we found somatic hybrids with mitochondrial DNA significantly different from either parent, as judged by analysis of fragment distribution after restriction enzyme digestion. The possible formation of altered mitochondrial DNA molecules as the result of parasexual hybrid production between two phylogenetically highly divergent plant species will be discussed. PMID- 24232796 TI - Analysis of early growth of guppy strains, Poecilia reticulata, with different color patterns. AB - The guppy, Poecilia reticulata, is economically the most important species of freshwater ornamental fish cultured in Singapore. About 30 strains with different color patterns and fin shapes are reared in guppy farms practising monoculture in Singapore. To compare the growth rates of domesticated strains with different color patterns, newborn fry of 11 strains were obtained on the same day from a single farm in Singapore and were reared experimentally in the laboratory for about 100 days. Each strain was distributed randomly into 4 tanks with 30 fish/tank. Weekly weighings of 10 fish/tank were made from 17 to 100 days of age. Three strains were homozygous for the autosomal recessive blond gene which gives rise to a pale yellow background pigmentation (bb). These blond strains had significantly smaller body weights than corresponding ones with the same color pattern but with the wild-type grey-brown background coloration due to the dominant allele (BB). The strains with the red tail pattern due to a dominant X linked gene (Rdt) had more rapid growth than those with other tail color patterns including the blue, black, green snakeskin and variegated. However, no significant differences were detected among the other color pattern strains. Thus among the strains studied, the blond strains were associated with slower growth while those with the red tail color were associated with faster growth. PMID- 24232797 TI - Brassica naponigra, a somatic hybrid resistant to Phoma lingam. AB - Brassica napus and B. nigra were combined via protoplast fusion into the novel hybrid Brassica naponigra. The heterokaryons were identified by fluorescent markers and selected by flow sorting. Thirty hybrid plants were confirmed by isozyme analysis to contain both B. nigra and B. napus chromosomes; of these, 20 plants had the sum of the parental chromosome numbers. A non-random segregation of the chloroplasts was found in the hybrids. Of 14 hybrid plants investigated, all had the B. napus type of chloroplast. The resistance to Phoma lingam found in the B. nigra cultivar used in the fusion experiments was expressed in 26 of the hybrid plants. The hybrids obtained in this study contain all of the three Brassica genomes (A, B and C) and have thus created unique possibilities for genetic exchanges between the genomes. Since most of the plants were fertile as well as resistant to P. lingam, they have been incorporated into conventional rapeseed breeding programs. PMID- 24232798 TI - Isozyme gene markers in Vicia faba L. AB - This study was conducted to assess the genetic basis of the variability observed for the glutamate oxaloacetate transaminase (GOT), Superoxide dismutase (SOD), esterase (EST), and malate dehydrogenase (MDH) isozyme systems in different open pollinated Vicia faba varieties. Individual plants showing contrasting zymogram patterns were simultaneously selfed and cross-combined. Crossing was unsuccessful in producing progeny, and only selfed progenies were suitable for genetical analysis of isozyme variability. Three zones of GOT activity were made visible. The isozyme of GOT-2 and GOT-3 zones were dimeric and under the control of three alleles at the Got-2 locus and two alleles at the Got-3 locus, respectively. The isozymes of the GOT-1 zone did not show any variability. Three zones of SOD isozyme activity were made visible. The isozymes occurring in the SOD-1 (chloroplastic isozyme form) and SOD-2 (cytosol isozyme form) zones were dimeric and under the control of two alleles at the Sod-1 and Sod-2 loci. The isozyme visualized in the SOD-3 zone (mitochondrial isozyme form) were tetrameric and under the control of two alleles at the Sod-3 locus. Apparently the isozymes made visible in the most anodal esterase zones EST-1, EST-2, and EST-3 were monomeric, and the occurrence of two alleles at each of two different loci explained the variability observed in the EST-2 and EST-3 zones. For MDH, only two five-banded zymogram pattern types were found, and every selfed progeny showed only one of the two zymogram type, indicating that each individual possessed fixed alleles at the loci controlling MDH isozyme. Got-2, Got-3, Sod-1, Sod-2, and Sod-3 appear to be five new isozyme gene markers that can be useful in Vicia faba breeding for linkage study, varietal fingerprinting, outcrossing rate estimate, and indirect selection for quantitative characters. PMID- 24232799 TI - DNA fingerprinting: a tool for determining genetic distances between strains of poultry. AB - DNA fingerprinting, a technique based on the detection of hypervariable minisatellite regions in DNA restriction fragments, was tested for its applicability to conduct population genetics in poultry. Using MspI digestion and phage M13 DNA as a probe, between 25 and 35 minisatellite-containing DNA fragments were observed per bird. Comparison of the banding pattern of offspring with their parents revealed that the bands were inherited as stable genetic traits. The variability of the DNA fingerprinting pattern was reduced in inbred strains. DNA fingerprints of chickens from five well-defined populations of known genetic relationships were analyzed and indices of genetic distances were computed. They correctly reflected the history of these strains, indicating that DNA fingerprinting may be a powerful tool to characterize genetic relationships between different breeding populations of the same species. PMID- 24232800 TI - Comparative and genetic studies of isozymes in resynthesized and cultivated Brassica napus L., B. campestris L. and B. alboglabra Bailey. AB - Enzyme electrophoresis was used to compare newly resynthesized Brassica napus with its actual parental diploid species, B. campestris and B. alboglabra. Comparisons were also made with cultivated B. napus. Of the eight enzyme systems assayed, four were monomorphic (hexokinase, malate dehydrogenase, mannose phosphate isomerase and peroxidase), whereas the remaining four were polymorphic (glucosephosphate isomerase, leucine aminopeptidase, phosphoglucomutase and shikimate dehydrogenase), when comparisons were made within or between species. The polymorphic enzyme patterns observed in the newly resynthesized B. napus disclosed that the homoeologous loci contributed by the parental species were expressed in the amphiploid. Analysis of the glucosephosphate isomerase enzyme in a breeding line (Sv 02372) of B. napus indicated that, in this case, the gene originating from B. campestris was switched off whereas that of B. oleracea was expressed. Duplicated enzyme loci were observed in B. campestris and B. alboglabra, thus providing additional evidence to support the hypothesis that these species are actually secondary polyploids derived from an unknown archetype of x=6. PMID- 24232801 TI - Differential male reproductive success in Douglas fir. AB - Differential male reproductive success was studied in clones at two seed orchards of Douglas fir, Pseudotsuga menziesii (Mirb.) Franco. The performance of tester pollen parents was compared in controlled pollinations with two-parent pollen mixes. Marker pollen homozygous for a rare IDH allele was the genetic marker in each pollen mix. The resulting seeds were analyzed electrophoretically. At both seed orchards, the proportion of seeds sired by tester pollen significantly varied among the tester pollen parents. Tester pollen parents did not perform the same across all seed parents. The significant interaction effect was evidence of male-female complementarity. These results suggest a genetic basis to differential male reproductive success in Douglas fir. PMID- 24232802 TI - Comparative performance of bread wheat and hexaploid triticale cytoplasms. AB - Thirteen wheat-like advanced-generation triticale x wheat derivatives, having tetraploid wheat cytoplasm from triticale, were reciprocally crossed with three improved bread wheats, and the resulting F1s were evaluated for determining the comparative performance of the bread wheat and triticale cytoplasms for different traits. Significant reciprocal differences in the mean performance were observed for days to heading, days to maturity, spikes/plant, flag-leaf area, peduncle length, plant height, spike length, grains/spike, 1,000-grain weight, grain yield and grain protein content, and most of them were in favour of hexaploid wheat cytoplasm. However, this superiority of the hexaploid cytoplasm was not universal for a particular trait, implying that the differences in the performance of the evaluated reciprocal crosses depended not solely on the cytoplasmic background, but also on the interplay of the specific genotype with the cytoplasm. PMID- 24232803 TI - The characterization and comparative analysis of high-molecular-weight glutenin genes from genomes A and B of a hexaploid bread wheat. AB - Two high-molecular-weight subunit (HMWS) glutenin genes from the A and B genomes of the hexaploid bread wheat Triticum aestivum L. cv Cheyenne have been isolated and sequenced. Both of these genes are of the high Mr class (x-type) of HMW glutenins, and have not been previously reported. The entire set of six HMW genes from cultivar Cheyenne have now been isolated and characterized. An analysis of the Ax and Bx sequences shows that the Ax sequence is similar to the homoeologous gene from the D genome, while the Bx repeat structure is significantly different. The repetitive region of these proteins can be modelled as a series of interspersed copies of repeat modifs of 6, 9, and 15 amino acid residues. The evolution of these genes includes single-base substitutions over the entire coding region, plus insertion/deletions of single or blocks of repeats in the central repetitive domain. PMID- 24232804 TI - A comparison of Hordeum bulbosum-mediated haploid production efficiency in barley using in vitro floret and tiller culture. AB - A high efficiency of Hordeum bulbosum-mediated haploid production in barley has been achieved using a floret culture technique in which florets pollinated with Hordeum bulbosum are cultured on modified N6 media containing 0.5 mg/l kinetin and 1.2 mg/l2,4-D. Cultures were maintained at 25 degrees C with a 16 h photoperiod for 9 days before embryo rescue. In a comparison of haploid production efficiency using five F1 hybrids from winter x winter and winter x spring barley crosses, 41.6 haploid plants/100 florets pollinated were produced using floret culture. Using detached tiller culture, 13.5 haploid plants/100 florets pollinated were produced. Higher efficiencies achieved with floret culture are attributed to the formation of larger, differentiated embryos. Such embryos lead to higher frequencies of plant regeneration. The F1 from a winter x winter cross was inferior in haploid production compared to F1s from winter x spring crosses. No genotype x technique interaction was observed. PMID- 24232805 TI - Position-specific effects in the mutagenic action of mitomycin C on the chromosomes of Hordeum vulgare L. AB - The mutagenic action of mitomycin C (MMC) on the chromosomes of two reconstructed karyotypes of barley was studied. MMC-induced chromatid aberrations were found to be distributed non-randomly along the chromosomes. The regions situated next to the secondary constrictions of chromosomes 6 and 7 appeared to be clearly pronounced aberration "hot spots". In these segments, intercalary deletions and duplication-deletions were the most frequently induced aberration types. The comparative analysis of the frequency and localization of MMC-induced aberrations in the chromosomes of the two karyotype variants, which differ from each other by the position of the "hot spot" segments, provided new evidence about the influence of the segment transposition on the "hot spot" expressivity. The most remarkable finding obtained in the study is that the size of the segment involved in both intercalary deletions and duplication-deletions proved to be strongly affected by the structural peculiarity of the reconstructed chromosome. The possible reasons underlying this finding are discussed. PMID- 24232806 TI - Phenotypic polymorphism and allele differentiation of isozymes in fodder beet, multigerm sugar beet and monogerm sugar beet. AB - Thirteen enzymes (MDH, SDH, LAP, PGM, PX, IDH, GPI, 6PGD, APH, GOT, GDH, ME and SOD) of 3 cultivated beet (B. vulgaris L.) gene pools, comprising 12 accessions of fodder beet, 11 of old multigerm sugar beet and 10 of modern monogerm sugar beet, were investigated using horizontal starch gel electrophoresis. Eleven accessions of primitive or wild B. vulgaris were also included for the comparison of isozymes. Variation in isozyme phenotypes was investigated to detect diversity in the three cultivated forms of beet. Phenotypic variation was observed in all except ME and SOD, which were monomorphic. A high degree of phenotypic polymorphism (Pj) was found in GDH, PGM, IDH, APH and MDH. Differences in phenotypic polymorphism in MDH, GPI and PX were recognized between fodder beet and both sugar beet groups. Average polymorphism for 13 enzymes in both sugar beets was significantly higher than that in fodder beet. For 13 enzymes, the existence of high isozyme diversity in both sugar beet gene pools was revealed. Allele frequencies in 13 alleles of five enzyme-coding loci, Lap, Px-1, Aph-1, Got-2 and Gdh-2, were investigated. New alleles, Px-1 (1) and Got-2 (1), were found in fodder beet accessions. No significant differences of average allele frequencies of five loci between fodder beet and both sugar beets were recognized. Several unique alleles and different isozyme phenotypes were observed in the accessions of B. vulgaris ssp. macrocarpa and ssp. adanensis. Future utilization of cultivated beet gene pools for sugar beet breeding is discussed from the viewpoint of genetic resources. PMID- 24232807 TI - Introgression in Brassica napus for adaptation to the growing conditions in Bangladesh. AB - Among the oleiferous Brassicas, B. napus has the highest seed and oil productivity. As it is a species adapted to the temperate regions, its spring type is either unable to flower or flowers too late in the short - day winter (rabi) season of the subtropics. B. napus (genome AACC) is an amphidiploid between B. campestris (AA) and B. oleracea (CC), and shares one genome with the other allotetraploids B. juncea (AABB) and B. carinata (BBCC). While B. napus lacks ecotypes adapted to the subtropics, the other four species are well represented in this climatic zone. Reciprocal crosses with or without one direct backcross to B. napus have been carried out with the intention of transfering short-day adaptability. The aim was to introgress the A genome of carefully selected early representatives of B. campestris and B. juncea with the corresponding genome in B. napus, and similary the C genome from B. oleracea and B. carinata with the analogous genome in B. napus. B. campestris, B. juncea and the clearly later species, B. oleracea var 'alboglabra' and B. carinata, seem to be almost equally effective in introgressing the appropriate earliness necessary for growth in Bangladesh. One backcross sligthly delayed segregation of early types. Convergent crosses did not result in the transgression of earliness, which was unexpected since the inheritance of flowering and maturity indicated a polygenic regulation. This result is partly explained by assuming dominant oligogenic control of the photoperiodic response. Introgression of earliness with the C genome doesn't seem to be necessarily related with the earliness of the donor species. Intergenomic interactions may be important. Interesting new lines were selected with high yield. Thus there is a good probability that Bangladesh will have a new oil crop. As these lines were observed to be early in Sweden as well, they could potentially push rapseed cultivation further north in temperate regions where the growing period is limited by short summers. PMID- 24232808 TI - Low temperature acclimation and treatment with exogenous abscisic acid induce common polypeptides in Arabidopsis thaliana (L.) Heynh. AB - Exogenously applied abscisic acid (ABA) induced frost hardening of Arabidopsis thaliana (L.) Heynh. The freezing tolerance of A. thaliana plantlets treated with ABA (15 mg/l) at a non-acclimating temperature (20 degrees C) appeared to increase even more rapidly than following a low temperature (4 degrees C) acclimation. Analysis of in vivo-labelled soluble proteins by two-dimensional gel electrophoresis revealed several low temperature - or ABA - induced proteins, which where not produced in non-acclimated plants. A subset of these proteins was induced by both low temperature and ABA treatments, suggesting that they might be directly involved in the frost hardening process in A. thaliana. PMID- 24232809 TI - Studies of isozymes in oat species. AB - Starch and polyacrylamide gel electrophoresis of seven isozyme systems was investigated as a means of identifying wild and cultivated species of Avena with different ploidy levels. By examining the characteristic isoenzymatic patterns, it was shown that there was considerable variability within the different species. However, it was nevertheless possible to unequivocally identify the species of wild oats and to distinguish between the different species belonging to the same genomic set, thus providing a definitive reference technique for the identification of Avena species in seed-testing laboratories. The relationships between Avena species were inferred from the electrophoresis data. The divergence of the A. maroccana - A. murphyi complex and its contribution to the AACC genomes are emphasized. PMID- 24232810 TI - Hybrid necrosis in triticale and the expression of necrosis genes in allopolyploids. AB - The occurrence in triticale of four different genes causing hybrid necrosis is described: Ne1 and Ne2 in the B genome of wheat and Ner1 and Ner2 in the rye genome. Hybrid necrosis develops due to dominant complementary interaction of two genes. This interaction in triticale, however, may take place not only between genes belonging to the same genome but also between genes of different genomes. In triticale, these genes can cause hybrid necrosis in four different combinations. The inheritance of the phenomenon in triticale is, therefore, more complicated than it is in wheat or rye. To avoid hybrid necrosis in triticale, attention should be paid that no necrosis genes are introduced into the primary triticale stocks from the wheat and rye parents. The expression of necrosis genes is influenced by the level of ploidy. Any additional genome - A, B, D, or R - may exert a suppressing effect on the expression of necrosis genes. Therefore, when identifying genotypes of triticale with regard to their necrosis genes, the level of ploidy has to be accounted for. Moreover, the present results illustrate that gene expression in polyploids is not only determined by interactions with other single genes but that it may also be modified by the total genotype of the respective individual. PMID- 24232811 TI - Genetic variability in Plantago species in relation to their ecology : 4. Ecotypic differentiation in P. major. AB - Twelve Plantago major plants, good representatives of their populations, appeared to be genetically different for several characters which are important for adaptation to the respective habitat conditions. These characters are: juvenile growth, leaf morphology, production of secondary rosettes, flowering time, seed production, seed size and adult leaf production. The adaptive value of some of these characters was investigated by transplantation experiments in the field and by intraspecific competition experiments. The roadside type of ssp. major was adapted to trampling by being erect and elastic. The lawn type of ssp. major was adapted to a short, frequently cut, vegetation by being prostrate and by producing leaves with short petioles throughout the growth season. In the natural situations in which ssp. pleiosperma occurs, growth rate and first-year seed production of this subspecies were considerably higher than that of ssp. major. In a number of experiments, F1s and F2s were included, derived from crosses between the original plants. The F1s were generally rather well adapted to both parental habitats, whereas the F2s appeared to be less fit. The various alternatives in spending resources relevant for fitness optimization in different habitats are discussed. PMID- 24232812 TI - Comments on: "Changes in wall shear stress magnitude after aneurysm rupture" by Kenichi Kono, Nagatsuki Tomura, Ryo Yoshimura and Tomoaki Terada, Acta Neurochir (2013) 155:1559-1563, DOI 10.1007/s00701-013-1773-2. PMID- 24232813 TI - [Translational research in gestational diabetes mellitus and mild gestational hyperglycemia: current knowledge and our experience]. AB - Maternal diabetes constitutes an unfavorable environment for fetal-placental and embryonic development. It is has important repercussion in modern obstetrics, since it is associated to an increased risk of neonatal and maternal morbidity, and it still is a significant medical challenge. The increased occurrence of diabetes worldwide, the increase in diabetes type 2 in women at reproductive age and the crossed generation of intrauterine programming for diabetes type 2 are the bases for the growing interest in utilization of diabetic experimental samples, with the aim to acquire knowledge about the mechanisms that induce development alterations in gestational diabetes. Several studies have shown the benefits of diabetes prevention, with interventions in lifestyle, metabolic improvement and control of cardiovascular risk factors to substantially prevent the complications of this devastating disease. Despite these findings, the recent revolution in the scientific knowledge, and the infinite number of new therapies for diabetes, there is still a large gap between what was learned through research and what is really done in public, clinical and community health. The negative economic impact of this complacency in people, families, and national economies is alarming. It is expected that translational research in the binomial diabetes and pregnancy are implemented in centers of excellence, in both basic and applied research, and complemented by multicenter clinical studies, conducted in a pragmatic way to increase the level of scientific evidence with more reliable diagnostic and propaedeutic resources. PMID- 24232814 TI - Prevalence of vitamin D deficiency is higher in patients with Paget's disease of bone compared with age-matched controls. AB - OBJECTIVE: To investigate if vitamin D deficiency is more prevalent in patients with Paget's disease of bone (PDB) than in age-matched controls. SUBJECTS AND METHODS: We measured serum 25-OHD in 28 untreated patients with PDB and two control groups: 284 elderly men from an ongoing cohort from our department, and 151 postmenopausal women seen in our outpatient clinic for routine medical evaluation. RESULTS: The mean +/- SD serum 25-OHD was significantly lower in subjects with PDB (23.76 +/- 6.29 ng/mL) than in the control groups of elderly men (27.86 +/- 13.52 ng/mL) and postmenopausal women (30.30 +/- 9.59 ng/mL), p = 0.015. The prevalence of vitamin D deficiency considering a cut-off point of serum 25-OHD < 30 ng/mL was 85.7% in patients with PDB, and in elderly men and postmenopausal women it was 66.7 % and 54.3%, respectively (p < 0.001). CONCLUSION: These results suggest a high prevalence of hypovitaminosis D in patients with Paget's disease living in the tropics. PMID- 24232815 TI - Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid lowering efficacy and safety of statin therapy. AB - OBJECTIVE: The aim of the present study was investigate the association between six genetic variants in the nuclear receptor genes PPARA, RXRA, NR1I2 and NR1I3 and the lipid-lowering efficacy and safety of statin therapy. SUBJECTS AND METHODS: The study was carried out on 240 Brazilian hypercholesterolemic patients on simvastatin and atorvastatin therapy. The polymorphisms were analyzed by PCR based methods. RESULTS: The NR1I3 rs2307424 genotype distribution was different between subjects with and without adverse drug reactions. Among subjects in the ADR group, no T/T homozygotes were observed for this polymorphism, while in the non-ADR group the frequency of this genotype was 19.4% (P = 0.007, after multiple testing corrections P = 0.042). CONCLUSION: The polymorphisms investigated in PPARA (rs1800206), RXRA (rs11381416), and NR1I2 (rs1523130) did not influence the lipid-lowering efficacy and safety of statin. Our results show the possible influence of NR1I3 genetic variant on the safety of statin. PMID- 24232816 TI - [Obesity: main risk factor for systemic arterial hypertension in Brazilian adolescents from a cohort study]. AB - OBJECTIVE: To identify the prevalence and factors associated with hypertension in adolescents. SUBJECTS AND METHODS: Cross-sectional study of 1,716 adolescents of a cohort study, aged from 10 to 16 years old sociodemographic, economic, and lifestyle characteristics were obtained from an interview, and birth weight from hospital records. Hypertension was defined as systolic or diastolic blood pressure above the 95th percentile according to the classification recommended by the Second Task Force High Blood Pressure in Children and Adolescents. Nutritional status was diagnosed by body mass index (BMI), according to the z score from curves published by the World Health Organization. Waist circumference was measured at the natural waist. The association between hypertension and the explanatory variables was measured using logistic regression. RESULTS: The adolescents interviewed represent 71.4% of the baseline, and 50.7% of them were males. The prevalence of hypertension was 11.7%. In the multivariate analysis, after adjustment for age sex and skin color, hypertension was associated with obesity [OR = 2.27, (95%) CI = 1.64 to 3.14] but not associated with waist circumference after adjusting for BMI. Early life factors were not associated with hypertension in adolescence. CONCLUSION: The results show an association between obesity and hypertension among adolescents. PMID- 24232817 TI - [Evaluation of bone mineral density in female adolescents with eating disorders]. AB - OBJECTIVE: To evaluate lumbar bone mineral density (BMD) in girls with eating disorders in the beginning of the treatment, at six months, and after one year of treatment. SUBJECTS AND METHODS: This prospective study involved 35 female adolescents with AN or EDNOS treated during one year. Lumbar (L1-L4) bone mineral density by DXA was performed in the beginning of treatment, at six months, and after one year of treatment. RESULTS: There was improvement in weight, length, BMI, bone age (p < 0.001), and 70% of the adolescents with secondary amenorrhea had their menstrual cycles restored. However, the Z-score of lumbar BMD did not show differences during one year of follow-up (p = 0.76). CONCLUSION: The recovery of BMD does not occur together with the restoration of hypothalamic pituitary-gonadal axis. PMID- 24232818 TI - [Butyrylcholinesterase activity and cardiovascular risk factors in obese adolescents submitted to an exercise program]. AB - OBJECTIVE: To evaluate the effect of 12 weeks of physical exercise (PE) on cardiovascular risk factors and BChE activity in obese adolescents. SUBJECTS AND METHODS: The sample consisted of 24 obese adolescents and 51 normal weight controls. The following variables were measured in the initial stage and after 12 weeks: weight, height, BMI, waist circumference (WC), fat percentage (% F), maximal oxygen uptake (VO2max), systolic (SBP) and diastolic (DBP) blood pressure, glucose (GLY) and insulin (INS) at baseline and after 120 min, triacylglycerol (TG), total cholesterol (TC), LDL cholesterol, HDL cholesterol, and BChE activity (kU/l). RESULTS: After the intervention, there was significant reduction in BMI, WC, %F, TG, GLI 120, INS 120 min, and BChE activity. CONCLUSION: The reduction in BChE activity, observed after physical exercise, was accompanied by the reduction of the variables associated with cardiovascular risk and obesity, indicating that BChE can be used as a secondary marker for the risk associated with early onset obesity. PMID- 24232819 TI - Evolution of thyroid cancer mortality in adults in Brazil. AB - OBJECTIVE: To assess the trend of thyroid cancer mortality in Brazil between 1980 and 2010. MATERIALS AND METHODS: An ecological study of time series. Mortality rates for thyroid cancer adjusted by age according to gender were calculated between 1980 and 2010. Data were analyzed by three distinct strategies: polynomial regression, joinpoint analysis, and moving averages. RESULTS: Over 70% of deaths occur in the elderly, regardless of sex. Among young adults, the mortality rate is low, with no difference between men and women. Among mature adults and elderly, mortality is increasing, and significantly, for women. There is a trend of decreasing mortality in all female adults and overall population, and in males and 40-59 years and overall population, both excluding the elderly, with statistical significance. CONCLUSION: Knowledge about trends allows setting priorities and allocating resources toward positive changes in this scenario in the Brazilian population. PMID- 24232820 TI - [Diabetes: time to redefine goals?]. AB - OBJECTIVE: The aim of this study was to assess if the A1c goals from the Brazilian Diabetes Society (SBD) were compatible with their goals for blood glucose. MATERIALS AND METHODS: An online simulation (AIDA) was used to simulate a hypothetical patient with blood glucose values similar to the SBD's goals. Average glucose was calculated from generated blood glucose values, and then converted to the corresponding A1c value, using the ADA online calculator. Other glycemic profiles, using different levels of blood glucose, were also simulated in order to assess which would be the A1c value associated with each profile. RESULTS: Glycemic goals proposed by the SBD (fasting glucose < 100 mg/dL, preprandial < 110 mg/dL, and postprandial < 140 mg/dL), were associated with an A1c of 5.9%, much lower than the goal of 7% recommended by the SBD. This demonstrates incompatibility among A1c and blood glucose goals proposed by the SBD. Such A1c levels are associated with increased mortality among high-risk patients. CONCLUSIONS: Besides recommending different A1c goals for different patients, the SBD should probably review its recommendations and adopt different blood glucose goals that are compatible with the proposed A1c goals, making therapeutic targets clearer. PMID- 24232821 TI - Physical activities in daily life and functional capacity compared to disease activity control in acromegalic patients: impact in self-reported quality of life. AB - OBJECTIVE: To evaluate the quality of life and its association with daily physical activity and disease control in acromegalic patients. SUBJECTS AND METHODS: A cross-sectional, case series study, composed of 42 patients recruited from the Neuroendocrinology Unit of the University Hospital of Brasilia. Level of physical activity was accessed by the International Physical Activity Questionnaire (IPAQ 6-short-form), which evaluates the weekly time spent on physical activity of moderate to vigorous intensity in different contexts of life. Quality of life was evaluated by The Medical Outcome Study Questionnaire Short Form (SF-36). Data was compared to growth hormone (GH) and insulin-like growth factor (IGF-1) levels. Students' t test and Fisher test were used, p < 0.05, SPSS 17.0. RESULTS: Twenty-two women, aged 51.33 +/- 14.33 and 20 men, aged 46.2 +/- 13.18 were evaluated. Arthralgia was present in 83% of cases. In men, the most common sites of pain were the knees (73%), spine (47% lumbar, and 53% thoracic and cervical segments), hands and wrists (40%). Higher scores on SF-36 were observed in patients with intermediate or high levels of physical activity, in the domains social functioning (75 CI 57.3-92.6), general health (75.5 CI 60.4 90.5), mental health (70 CI 57.8-82.1). CONCLUSIONS: In this study, the presence and severity of physical disability and pain were not associated with initial GH and IGF-1 levels or time of exposure to GH excess. However, the patients considered controlled, with normal a normal age-adjusted IGF-1, presented higher scores in SF-36, in physical and emotional domains, compared with patients with persistent hypersomatotrophism. These findings suggest benefits of metabolic control in self-reported quality of life. PMID- 24232822 TI - Giant macroprolactinoma and pregnancy. AB - Prolactinomas are a common cause of gonadal dysfunction and infertility. We present the case of a 38-year-old woman with history of amenorrhea and infertility. At seven weeks of pregnancy she presented neuro-ophthalmologic complaints of headaches, diplopia, and right ptosis. The work-up study revealed an invasive pituitary macroadenoma with a maximum diameter of 9 cm and serum prolactin of 25,800 ng/mL (3-20). At 12 weeks, she was referred to the Endocrinology Department of the Coimbra University Hospital and started therapy with bromocriptine, initially 5 mg/day and then at crescent doses. Hyperprolactinemia was rapidly and drastically reduced to 254 ng/mL three weeks after taking bromocriptine 15 mg/day. Tumoral volume was reduced and there was improvement of III pair paresis. At 38 weeks, a male healthy baby was born. This is a relevant clinical case that illustrates the efficacy and safety of bromocriptine therapy during pregnancy, even in severe cases like this one. PMID- 24232823 TI - Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder. AB - Mutation on NROB1 (DAX1) gene can cause different phenotypes of adrenal insufficiency in infancy. Long-term evolution of these patients shows that it is possible to have an association with hypogonadotropic hypogonadism. In this article we describe the evolution of a patient with NROB1 gene mutation, diagnosed with a mild form of adrenal insufficiency, and we highlight the presence of hypogonadotropic hypogonadism and short stature, besides the presence of attention deficit disorder. Such associations should make physicians aware during the follow-up of patients with this disease. PMID- 24232824 TI - An intrasellar germinoma with normal tumor marker concentrations mimicking primary lymphocytic hypophysitis. AB - Intracranial germinomas (GE) are malignant neoplasms most commonly found in the suprasellar region, which may cause anterior and particularly posterior pituitary hormone deficits with central diabetes insipidus (DI). Differential diagnosis of pituitary stalk thickening includes granulomatous, inflammatory, infectious, and neoplastic lesions. Although careful analysis of clinical, laboratory, and imaging findings may facilitate the diagnosis, transsphenoidal biopsy is indicated to confirm the disease, as the correct diagnosis directs the appropriate treatment. PMID- 24232825 TI - Lithium and phosphorilation cell reactions. PMID- 24232826 TI - Response to the letter: Endocrine disturbances related to the use of lithium. PMID- 24232827 TI - Cranioplasty with polymethylmethacrylate prostheses fabricated by hand using original bone flaps: Technical note and surgical outcomes. AB - BACKGROUND: Decompressive craniectomies (DC) mandate future cranioplasties, accounting for the large array of biomaterials for this purpose. Polymethylmethacrylate (PMMA) is a very reliable thermoplastic that can be prefabricated or even molded intraoperatively to create an adequate prosthesis. Preformed PMMA implants made by hand have been superseded by newer 3-D printed implants, but this is accompanied by higher costs and timing issues, apart from having limited availability in developing and third-world countries. METHODS: A total of 26 patients were operated over a span of 11 years. A total of 26 custom hand-made PMMA prostheses were fabricated using original bone flaps with the aid of a prosthodontist, in a process that took approximately 70 minutes for each implant. The result was an exact duplication of the patient's bone flap. RESULTS: Of the 26 patients who underwent cranioplasty, the majority of patients were males, with a mean age of 39.2 years and traumatic brain injury as main indication for DC. After a mean interval of 2.4 months, all 26 patients underwent a cranioplasty and prosthesis placement. Only two patients (7.6%) suffered from direct cranioplasty-related complications after a median follow-up of 10.4 months. Median Glasgow Outcome Scale scores improved significantly from 3 to 4 after cranioplasty (P = 0.008). CONCLUSION: Prefabrication of custom PMMA prostheses by hand when original bone flaps are available is an excellent alternative to newer 3-D printing techniques, because it is relatively cheaper, less time consuming, and offers excellent results in terms of anatomical reconstruction and improvement of neurological function in long-term follow-ups. PMID- 24232828 TI - Interactive multigrid refinement for deformable image registration. AB - Deformable image registration is the spatial mapping of corresponding locations between images and can be used for important applications in radiotherapy. Although numerous methods have attempted to register deformable medical images automatically, such as salient-feature-based registration (SFBR), free-form deformation (FFD), and demons, no automatic method for registration is perfect, and no generic automatic algorithm has shown to work properly for clinical applications due to the fact that the deformation field is often complex and cannot be estimated well by current automatic deformable registration methods. This paper focuses on how to revise registration results interactively for deformable image registration. We can manually revise the transformed image locally in a hierarchical multigrid manner to make the transformed image register well with the reference image. The proposed method is based on multilevel B spline to interactively revise the deformable transformation in the overlapping region between the reference image and the transformed image. The resulting deformation controls the shape of the transformed image and produces a nice registration or improves the registration results of other registration methods. Experimental results in clinical medical images for adaptive radiotherapy demonstrated the effectiveness of the proposed method. PMID- 24232829 TI - Trabeculectomy for open-angle glaucoma in phakic eyes vs in pseudophakic eyes after phacoemulsification: a prospective clinical cohort study. AB - IMPORTANCE: Whether pseudophakic eyes are resistant to trabeculectomy remains unknown. OBJECTIVE: To determine the effect of previous phacoemulsification on surgical success of trabeculectomy with mitomycin C for open-angle glaucoma. DESIGN, SETTING, AND PARTICIPANTS: Prospective clinical cohort study at Kumamoto University Hospital, Kumamoto, Japan, among patients 55 years or older having open-angle glaucoma with intraocular pressure (IOP) of 22 mm Hg or higher, including 39 phakic eyes (phakic group) and 25 pseudophakic eyes after phacoemulsification (pseudophakic group). INTERVENTION: Trabeculectomy with mitomycin C was performed. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the probability of success at 1 year after trabeculectomy. Surgical failure was defined as the following 3 IOP levels: 21 mm Hg or higher (criterion A), 18 mm Hg or higher (criterion B), and 15 mm Hg or higher (criterion C). Secondary outcome measures included IOP, the number of postoperative antiglaucoma medications, and the number of laser suture lysis procedures, as well as postoperative complications. RESULTS: The probabilities of success at 1 year in the phakic vs pseudophakic groups were 95% vs 74% for criterion A (P = .02), 84% vs 62% for criterion B (P = .04), and 67% vs 53% for criterion C (P = .10). Only pseudophakia was significantly associated with outcome in the multivariable analysis for criterion A (relative risk, 9.37) and for criterion B (relative risk, 5.52) (P = .01 for both). Postoperative IOP in the pseudophakic group was significantly higher than that in the phakic group at 6 months (P = .03) and 9 months (P = .047) after trabeculectomy. No significant difference between groups was noted in postoperative complications or in the number of postoperative antiglaucoma medications or the number of laser suture lysis procedures. CONCLUSIONS AND RELEVANCE: Among patients with open-angle glaucoma, trabeculectomy with mitomycin C in pseudophakic eyes after phacoemulsification for target IOP of less than 21 mm Hg or less than 18 mm Hg is less successful compared with that in phakic eyes. No significant difference between phakic and pseudophakic eyes was observed for secondary outcome measures other than IOP. TRIAL REGISTRATION: clinicaltrials.gov Identifier: University Hospital Medical Information Network Clinical Trials Registry of Japan UMIN000001196. PMID- 24232830 TI - Investigations on the crystal plane effect of ceria on gold catalysis in the oxidative dehydrogenation of alcohols and amines in the liquid phase. AB - Gold nanoparticles supported on ceria{110} crystal planes were more reactive than on ceria{111} and {100} in the oxidative dehydrogenation of alcohols. Kinetic analysis and a Hammett plot suggest that hydride transfer is involved, and the cationic gold is catalytically active. PMID- 24232831 TI - New treatment strategy for cupulolithiasis associated with benign paroxysmal positional vertigo of the lateral canal: the head-tilt hopping exercise. AB - This study was performed to determine whether a novel treatment was effective against cupulolithiasis associated with benign paroxysmal positional vertigo (BPPV) of the lateral semicircular canal, which is characterized by apogeotropic direction-changing nystagmus. We herein describe our head-tilt hopping (HtH) exercise, which is designed to release otoconial debris strongly adhered to the cupula. The subjects were trained to hop while tilting their heads laterally. They completed 3 to 5 exercise sessions per day over a 4-week period. Each session ended with a 20-hop trial. The HtH exercises were performed by 27 patients with intractable lateral canal BPPV who exhibited positional vertigo and persistent nystagmus beating toward the uppermost ear for more than 4 weeks, despite performing therapeutic head shaking in the horizontal plane maneuver. All the patients were subjected to the supine roll test before and immediately after the first trial as well as after 1 and 4 weeks of the program to evaluate the effect of the treatment on their apogeotropic nystagmus. Nystagmus of 9 (33.3 %) patients disappeared immediately after the first training session. After 1 and 4 weeks of the training, the number of patients that had experienced either of these improvements had increased to 15 (55.6 %) and 19 (70.4 %) subjects, respectively. These results suggest that HtH exercises aimed at releasing otoconial debris from the cupula are feasible as a new therapy for cupulolithiasis associated with intractable lateral canal BPPV. However, further studies for comparison with control are required to confirm these preliminary results. PMID- 24232832 TI - Calcium malate overproduction by Penicillium viticola 152 using the medium containing corn steep liquor. AB - In this study, after screening of eight fungal strains for their ability to produce calcium malate, it was found that Penicillium viticola 152 isolated from marine algae among them could produce the highest titer of calcium malate. At the same time, it was found that corn steep liquor (CSL) could stimulate calcium malate production and 0.5 % (v/v) CSL was the most suitable for calcium malate production. Under the optimal conditions, a titer of calcium malate in the supernatant was 132 g/l at flask level. During a 10-l fermentation, a titer of 168 g/l, a yield of 1.28 g/g of glucose, and a productivity of 1.75 g/l/h were reached within 96 h of the fermentation, and 93.4 % of the sugar was used for calcium malate production and cell growth, demonstrating that the titer, yield, and productivity of calcium malate by this fungal strain were very high and the fermentation period was very short. After analysis of the partially purified product with high-performance liquid chromatography, it was found that the main product was calcium malate. The results demonstrated that P. viticola 152 obtained in this study was the most suitable for developing a novel one-step fermentation process for calcium malate production from glucose on a large scale. PMID- 24232833 TI - Chemical and enzymatic approaches to the synthesis of optically pure ethyl (R)-4 cyano-3-hydroxybutanoate. AB - Ethyl (R)-4-cyano-3-hydroxybutanoate (HN) is an important chiral synthon for side chain of the cholesterol-lowering drug atorvastatin (Lipitor), which is the hydroxymethylglutaryl CoA reductase inhibitor. HN is also used as a synthon in the production of L-carnitine and (R)-4-amino-3-hydroxybutanoic acid. It is necessary to have a clear understanding of the synthesis process of HN for its extensive use. This review gives an overview of different synthetic strategies of optically active HN, including chemical and enzymatic approaches. The emphasis is focused mainly on the synthetic routes using biocatalysts, such as halohydrin dehalogenase, nitrilase, carbonyl reductase, and lipase. PMID- 24232834 TI - Ultrastructural localisation by protein A-gold immunocytochemistry of 5 enolpyruvylshikimic acid 3-phosphate synthase in a plant cell culture which overproduces the enzyme. AB - Recently we have shown that cultured cells of the higher plant Corydalis sempervirens Pers., adapted to growth in the presence of high concentrations of the herbicide glyphosate, a potent specific inhibitor of the shikimate pathway enzyme 5-enolpyruvylshikimic acid 3-phosphate (EPSP) synthase (EC 2.5.1.19, 3 phosphoshikimate 1-carboxyvinyltransferase) oversynthesize the EPSP synthase protein (Smart et al., 1985, J. Biol. Chem. 260, 16338-16346). We now report that the EPSP synthase protein can be detected in cells of the adapted as well as of the non-adapted strain by the use of protein A-colloidal gold immunocytochemistry. The overproduced EPSP synthase in the glyphosate-adapted cells is located exclusively in the plastid and we find no evidence for the existence of extra-plastidic EPSP synthase in either strain. PMID- 24232835 TI - Circadian changes in protein-synthesis rate and protein phosphorylation in cell free extracts of Gonyaulax polyedra. AB - The polysomal pattern of the dinoflagellate Gonyaulax polyedra, cultured under constant conditions, demonstrates a circadian rhythm. The relative amount of polysomes increases during the phase corresponding to the previous night period (=subjective night phase) when the rate of protein synthesis reaches its maximum (Cornelius et al., 1985, Planta 160, 365-370). Cell-free extracts were isolated at different circadian phase. The rate of protein synthesis in the extracts changed rhythmically in the same manner as the rate of protein synthesis in vivo. Substances in the postribosomal supernatants influenced the protein-synthesis rate of the cell-free system, depending on the phase when they were isolated: "night factors" stimulated protein synthesis in "day extracts" whereas "day factors" inhibited protein synthesis in "night extracts". These effects were abolished by heating the postribosomal supernatant. In-vitro phosphorylation in parallel probes showed changes in the pattern of phosphorylated proteins. Phosphorylation of one of the proteins (95 kDa) was decreased after addition of "night factor(s)" and increased after addition of "day factor(s)". Cyclic-AMP enhanced the rates of protein synthesis and phosphorylation in the day extracts. PMID- 24232837 TI - Combined electron-spin-resonance, X-ray-diffraction studies on phospholipid vesicles obtained from cold-hardened wheats : II. The role of free sterols. AB - The contents of free sterols and phospholipids in leaves of wheat, Triticum aestivum L., cultivars of different frost resistances, as well as the physical state of isolated phospholipids in the presence and absence of sterols, were compared before and after hardening. There was an inverse relationship between the sterol/phospholipid ratio and frost tolerance as a consequence of both a decrease in the free sterol, and an increase in the total phospholipid content. Sterol-sterol interactions were investigated using wide angle X-ray diffraction, while the phase behaviour of phospholipid vesicles was studied using the electron spin-resonance (ESR) technique. No sterol-sterol interactions at-10 degrees C were detected in vesicles obtained from the hardened most cold-tolerant cultivar (Miranovskaja 808), containing sterols in a ratio (0.08) found in the original lipid extracts. In contrast, when the sterol-phospholipid ratio in the vesicles was set to the level (0.39) found in the extracts of the most sensitive cultivar, Penjamo 62, the appearance of sharp reflexion rings at 4.5.10(-1), 4.8.10(-1) and 5.0.10(-1) nm indicated strong sterol-sterol interactions. The temperatures for the onset of phase separation for vesicles of identical sterol/phospholipid ratios found in lipid extracts of hardened Miranovskaja 808 were almost the same as those measured in purified phospholipids (-15 vs.-16 degrees C). In contrast, the temperature for the onset of phase separation of vesicles with a sterol/phospholipid ratio characteristic of hardened Penjamo 62 was shifted upwards (from-6 to-2 degrees C). Phase separation was not completed in the vesicles of Miranovskaja 808 in the temperature range scanned (-30 degrees C) but was shifted from-22 to-18 degrees C in the presence of sterols in the case of Penjamo 62. The results are discussed in terms of the composition and physical state of membranes in relation to survival at freezing temperatures. PMID- 24232836 TI - Combined electron-spin-resonance, X-ray-diffraction studies on phospholipid vesicles obtained from cold-hardened wheats : I. An attempt to correlate electron spin-resonance spectral characteristics with frost resistance. AB - Phospholipid multibilayers, obtained from two cultivars of thermally acclimated wheats of different frost resistances (Triticum aestivum L. cv. Penjamo 62, the sensitive cultivar, and T. aestivum L. cv. Miranovskaja 808, the frost-resistant cultivar), were investigated using electron-spin-resonance and X-ray-diffraction techniques. The former technique revealed two breaks in the motion of the spin labelled fatty acid 2-(14-carboxyte-tradecyl)-2-ethyl-4,4-dimethyl-3 oxazolidinyloxyl, for both cultivars (+3 degrees C,-17 degrees C and +5 degrees C,-18 degrees C, respectively) when grown at 22 degrees C. The resistant cultivar compensated for exposure to cold (+2 degrees C) by shifting the onset of the apparent phase-separation temperature from +3 degrees C to-16 degrees C. The sensitive cultivar was unable to do so. X-ray diffraction did not reveal fluid-to-gel transitions between +20 degrees C and-10 degrees C in any of the samples. The possible role of the formation of relatively ordered aggregates or clusters of lipid molecules discerned by spin probe within the otherwise freely dispersed liquid-like lipids is discussed in terms of freezing injury of plants. PMID- 24232838 TI - Partial characterization of an antheridiogen of Anemia mexicana: Comparison with the antheridiogen of A. phyllitidis. AB - An antheridiogen of Anemia mexicana Klotzsch has been partially characterized by combined gas chromatography-mass spectrometry and gas chromatography-Fourier transform/infra-red spectrometry. It is a C19-gibberellin(GA)-like compound with one carboxyl group, an exocyclic methylene group and a lactone ring. It also has one hydroxyl-group and one double-bond equivalent which has not been determined. On the basis of its mass spectrum, it is not identical to previously identified monohydroxy GAs with one ring double bond such as GA5, GA7, GA31 and GA62. By direct comparison of mass spectra, the antheridiogen of A. mexicana was also determined to be different from the antheridiogens of Anemia phyllitidis (L.) Swartz, Anemia hirsuta (L.) Swartz and Lygodium japonicum (Thunb.) Sw. PMID- 24232839 TI - The oxidation of extracellular NADH by sugarcane cells: Coupling to ferricyanide reduction, oxygen uptake and pH change. AB - Suspension-cultured cells of sugarcane (Saccharum sp. hybrids) did not oxidize exogenously supplied NADH in the absence of ferricyanide (potassium hexacyanoferrate [III]), whereas they did at a low rate in the presence of ferricyanide. Concomitantly, ferricyanide was reduced at a slow rate. Neither a pH change nor a change in respiration was caused by the addition of NADH and-or ferricyanide, but ferricyanide was a strong inhibitor of sugar transport. In contrast to cells, protoplasts rapidly oxidized exogenous NADH. This oxidation was accompanied by an increase in oxygen consumption and a net proton disappearance from the medium. Exogenous ferricyanide was reduced only slowly by protoplasts. Simultaneous presence of NADH and ferricyanide produced two effects: 1) a very rapid stoichiometric oxidation of NADH and reduction of ferricyanide until one of the reaction compounds was exhausted, and 2) a nearly instantaneous inhibition of the slower phase of NADH oxidation, which was observed in the presence of NADH but absence of ferricyanide. The extra oxygen consumption and the alkalinization of the medium, as observed with NADH, were also immediately stopped by ferric ions and ferrous ions. The presence of NADH and ferricyanide caused a fast stoichiometric acidification of the medium. These results were taken as evidence that the oxidation of NADH in the absence of ferricyanide is not related to the NADH-ferricyanide-coupled redox reaction. Furthermore, addition of NADH caused some uncoupling of the protoplasts, an effect which would explain the strong acidification of the cell cytoplasm and the inhibition of various transport systems. The NADH-oxidizing systems oxidized both the beta configurated pyridine nucleotide and the alpha-configurated form. Since NADH linked dehydrogenases usually do not work with alpha-NADH (with the exception of the endoplasmic-reticulum-bound electron-transport system), the observed activities could have been derived from contaminating membranes and dying protoplasts in the suspension. All reported reactions partly or predominantly occurred in the supernatant of the protoplast suspension and increased considerably during incubation of the protoplasts. The rates and quantities of oxygen consumption, pH change, and ferricyanide reduction fitted with NADH oxidation in a stoichiometric ratio, which implied that all these reactions occurred in the extracellular space, without involving transmembrane steps. No evidence for a physiological role in energization of the plasmalemma was found. PMID- 24232840 TI - Changes in respiration of mitochondria isolated from cotyledons of ethylene treated pea seedlings. AB - Treatment of intact, germinating pea (Pisum sativum L. cv. Homesteader) seedlings with ethylene enhanced the cyanide-resistant respiration of mitochondria isolated from the cotyledons. The level of enhancement depended on the concentration of ethylene. Thus, exposure to 0.9 MUl.l(-1) of ethylene in air for days 4-6 of germination had little effect on cyanide-resistant respiration, while exposure to 130 MUl.l(-1) increased it from 10 to 50 nmol O2.min(-1).(mg protein)(-1). The length of exposure to ethylene also affected the degree of enhancement. According to some literature data, lipoxygenase (EC 1.13.11.12) activity can be mistaken for cyanide-resistant respiration, but in our preparations of purified pea mitochondria ethylene had no effect on lipoxygenase activity, nor did the gas disrupt the outer mitochondrial membrane. Bahr and Bonner plots of respiration in the presence of salicylhydroxamic acid (SHAM) indicated that ethylene did not affect respiration proceeding via the cytochrome pathway. Thus, increases in total respiration in mitochondria from cotyledons of ethylene-treated pea seedlings reflect increases in cyanide-resistant respiration. PMID- 24232841 TI - Identification of somatic hybrids in plant protoplast fusions with monoclonal antibodies to plasma-membrane antigens. AB - Monoclonal antibodies generated by immunization with a plasma-membrane preparation from suspension-cultured cells of Nicotiana glutinosa L. were used in combination with fluoresceinor rhodamine-labeled goat anti-mouse immunoglobulins to identify heterokaryons in protoplast fusion procedures. Antibody labeling did not inhibit callus formation nor plantlet regeneration. The antibodies are non invasive and surface labeling provides clear optical discrimination of true heterokaryons from unfused aggregates as well as from parental protoplasts and homokaryons. Labeling is stable throughout fusion and hence by pre-labeling parental protoplast populations the strategy is both versatile and of general applicability. PMID- 24232842 TI - Changes in cell-cycle duration and growth fraction in the shoot meristem of Sinapis during floral transition. AB - The cell-cycle duration and the growth fraction were estimated in the shoot meristem of Sinapis alba L. during the transition from the vegetative to the floral condition. Compared with the vegetative meristem, the cell-cycle length was reduced from 86 to 32 h and the growth fraction, i.e. the proportion of rapidly cycling cells, was increased from 30-40% to 50-60%. These changes were detectable as early as 30 h after the start of the single inductive long day. The faster cell cycle in the evoked meristem was achieved by a shortening of the G1 (pre-DNA synthesis), S (DNA synthesis) and G2 (post-DNA synthesis) phases of the cycle. In both vegetative and evoked meristems, both-the central and peripheral zones were mosaics of rapidly cycling and non-cycling cells, but the growth fraction was always higher in the peripheral zone. PMID- 24232843 TI - Sequential patterns of intramural digestion of galactoxyloglucan in tamarind seedlings. AB - The structure and breakdown of galactoxyloglucan (GXG)-rich cells was studied from cotyledons of Tamarindus indicus L. The depletion of GXG was followed at different levels: quantitative, histochemical and cytochemical. At the ultrastructural level two probes were used: one general for polysaccharides (periodic acid - thiocarbohydrazide - silver proteinate test), the other specific for the terminal galactosyl residues of GXG (beta-galactosidase-gold complex). They were complemented by water-extraction of the GXG and analysis of the constituting monosaccharides by gas chromatography. Despite their collenchymateous aspect and the chemical similarity of the reserve GXG with the structural xyloglucan of growing walls, the thickened storage walls are not interpretable as being an hypertrophied primary wall. The tamarind cells produce an original type of wall construction in which GXGs are sequestered in a sort of homomolecular bulk. There is no evidence for intussusception of the molecules within a network of cellulose. The bulk of GXG is sandwiched between two thin layers: the outer is comparable to a regular primary wall, the inner behaves like a barrier during GXG withdrawal. Temporal and spatial patterns of GXG mobilisation lead to the definition of a sequence of stages of cell activities (premobilising, mobilising, postmobilising). They are synchronized with the growth of the seedling axis, the duration and characteristics of the stages being subordinated to the location of the cells within the organ. Cell lysis is initiated in close relationship with intramural cavities. The development of digestion pockets results in a highly digested wall. The barrier prevents any engulfing of the cytoplasm in the wall clefts and creates an increasing free space. The attack front of digestion is always sharp. During all steps, the monosaccharide composition remains stable. At the end of GXG depletion, the storage wall is withdrawn and cells are rendered in a parenchyma-like state. The breakdown is not a complete wall collapse but an original controlled and limited wall-thinning. The data lead to the speculation that the hydrolytic activities result from a complementation between precursors relinquished by the cytoplasm and factors already present in the storage wall. PMID- 24232844 TI - The uptake of acylated anthocyanin into isolated vacuoles from a cell suspension culture of Daucus carota. AB - Anthocyanin-containing vacuoles were isolated from protoplasts of a cell suspension culture of Daucus carota. The vacuoles were stable for at least 2 h as demonstrated by the fact that they showed no efflux of anthocyanin. The uptake of radioactively labelled anthocyanin was time-dependent with a pH optimum at 7.5, and could be inhibited by the protonophore carbonylcyanide m chlorophenylhydrazone. Furthermore, the transport was specific, since vacuoles from other plant species showed no uptake of labelled anthocyanin, and strongly depended on acylation with sinapic acid, as deacylated glycosides were not taken up by isolated vacuoles. Hence, it is suggested that the acylation of anthocyanin, which is also required for the stabilization of colour in vacuoles, is important for transport, and that acylated anthocyanin is transported by a selective carrier and might be trapped by a pH-dependent conformational change of the molecule inside the acid vacuolar sap. PMID- 24232845 TI - Preparation and characterization of monoclonal antibodies which recognise different gibberellin epitopes. AB - The production and characterization of high-affinity monoclonal antibodies (McAb) to gibberellins (GAs) is reported. Hybrid myelomas were derived from immunisations with conjugates in which immunogenic proteins were linked to GA1 at carbon-3 and to GA4 and GA9 at carbon-17. A series of McAb which display specificities allowing recognition of, and the discrimination between GA1, GA20, GA4 and GA9 is described. These McAb can be used in quantitative immunoassays for underivatised GAs. PMID- 24232846 TI - Characterization of carbon metabolism in Opuntia ficus-indica Mill. exhibiting the idling mode of Crassulacean acid metabolism. AB - Upon transfer from well-watered conditions to total drought, long-day-grown cladodes of Opuntia ficus-indica Mill. shift from full Crassulacean acid metabolism (CAM) to CAM-idling. Experiments using (14)C-tracers were conducted in order to characterize the carbon-flow pattern in cladodes under both physiological situations. Tracer was applied by (14)CO2 fumigations and NaH(14)CO3 injections during the day-night cycle. The results showed that behind the closed stomata, mesophyll cells of CAM-idling plants retained their full capacity to metabolize CO2 in light and in darkness. Upon the induction of CAM idling the level of the capacity of phosphoenolpyruvate carboxylase (EC 4.1.1.31) was maintained. By contrast, malate pools decreased, displaying finally only a small or no day-night oscillation. The capacity of NADP-malic enzyme (EC 1.1.1.40) decreased in parallel with the reduction in malate pools. Differences in the labelling patterns, as influenced by the mode of tracer application, are discussed. PMID- 24232847 TI - Expression of two nuclear genes encoding chloroplast proteins during early development of cucumber seedlings. AB - Cloned complementary DNA probes have been used to measure steady-state transcript levels for the small subunit of ribulose bisphosphate carboxylase-oxygenase (SSU) and the chlorophyll a/b-binding protein (LHCP) in cotyledons during early development of cucumber seedlings. Initial accumulation of trancripts to SSU occurs 2d after germination and is independent of light and developmentally programmed. Although transcripts accumulate in dark-grown tissues, their levels increase rapidly in light-grown cotyledons from day 4, coinciding with emergence above the soil, so that by day 6 levels are 2.4 times higher in light-grown compared with dark-grown cotyledons. In contrast, accumulation of transcripts to LHCP occurs only in light-grown cotyledons. Southern blot analysis of genomic DNA indicates that in cucumber there are one and two genes encoding SSU and LHCP, respectively, considerably fewer than in those other plant species that have been examined. Both LHCP genes are expressed in light-grown cotyledons. PMID- 24232848 TI - Characteristics of MgATP(2-)-dependent electrogenic proton transport in tonoplast vesicles of the facultative crassulacean-acid-metabolism plant Mesembryanthemum crystallinum L. AB - Membrane vesicles were isolated from mesophyll cells of Mesembryanthemum crystallinum in the C3 state and in the crassulacean acid metabolism (CAM) state. The distribution of ATP-hydrolysis and H(+)-transport activities, and the activities of hydroxypyruvate reductase and Antimycin-insensitive cytochrome-c reductase on continuous sucrose gradients was studied. For isolations carried out routinely a discontinuous sucrose gradient (24%/37%/50%) was used. Nitrate sensitive ATP-hydrolysis and H(+)-transport activities increased several-fold during the transition from C3 photosynthesis to CAM. Nitrate-sensitive ATPase showed a substrate preference for ATP with an apparent Km (MgATP(2-)) of 0.19 0.37 mM. In both C3 and CAM states the ATPase showed a concentration-dependent stimulation by the anions chloride and malate. However, the pH optima of the two states were different: the ATPase of C3- M. crystallinum had an optimum of pH 7.4 and that of CAM-M. crystallinum an optimum of pH 8.4. The optical probe oxonol-VI was used to demonstrate the formation of MgATP(2-)-dependent electric-potential gradients in tonoplast vesicles. PMID- 24232849 TI - Carotenoid and chlorophyll biosynthesis in isolated plastids from mustard seedling cotyledons (Sinapis alba L.) during etioplast-chloroplast conversion. AB - Etioplasts and etiochloroplasts, isolated from seedlings of white mustard (Sinapis alba L.) grown in continuous far-red light, and chloroplasts isolated from cotyledons and primary leaves of white-light-grown seedlings exhibit high prenyl-lipid-forming activities. Only the etioplasts and etiochloroplasts, and to a much lesser extent chloroplasts from cotyledons are capable of forming carotenes from isopentenyl diphosphate as substrate, whereas in chloroplasts from primary leaves no such activities could be detected. By subfractionation experiments, it could be demonstrated that the phytoene-synthase complex in etioplasts and etiochloroplasts is present in a soluble form in the stroma, whereas the subsequent enzymes, i.e. the dehydrogenase, cis-trans isomerase and cyclase are bound to both membrane fractions, the prolamellar bodies/prothylakoids and the envelopes. In good agreement with previous results using isolated chromoplasts and chloroplasts, it is concluded that the phytoene synthase complex may change its topology from a peripheral membrane protein in non-green plastids to a tightly membrane-associated protein in chloroplasts. This change is apparently paralleled by altered functional properties which render the complex undetectable in isolated chloroplasts. Further experiments concerning the reduction of chlorophyll a containing a geranylgeranyl side chain to chlorophyll a indicate that the light-induced etioplast-chloroplast conversion is accompanied by a certain reorganization of the polyprenoid-forming enzymatic equipment. PMID- 24232850 TI - Gibberellins in developing fruits of Pisum sativum cv. Alaska: Studies on their role in pod growth and seed development. AB - Gibberellins A1, A8, A20 and A29 were identified by capillary gas chromatography mass spectrometry in the pods and seeds from 5-d-old pollinated ovaries of pea (Pisum sativum cv. Alaska). These gibberellins were also identified in 4-d-old non-developing, parthenocarpic and pollinated ovaries. The level of gibberellin A1 within these ovary types was correlated with pod size. Gibberellin A1, applied to emasculated ovaries cultured in vitro, was three to five times more active than gibberellin A20. Using pollinated ovary explants cultured in vitro, the effects of inhibitors of gibberellin biosynthesis on pod growth and seed development were examined. The inhibitors retarded pod growth during the first 7 d after anthesis, and this inhibition was reversed by simultaneous application of gibberellin A3. In contrast, the inhibitors, when supplied to 4-d-old pollinated ovaries for 16 d, had little effect on seed fresh weight although they reduced the levels of endogenous gibberellins A20 and A29 in the enlarging seeds to almost zero. Paclobutrazol, which was one of the inhibitors used, is xylem-mobile and it efficiently reduced the level of seed gibberellins without being taken up into the seed. In intact fruits the pod may therefore be a source of precursors for gibberellin biosynthesis in the seed. Overall, the results indicate that gibberellin A1, present in parthenocarpic and pollinated fruits early in development, regulates pod growth. In contrast the high levels of gibberellins A20 and A29, which accumulate during seed enlargement, appear to be unnecessary for normal seed development or for subsequent germination. PMID- 24232851 TI - Some characteristics of terpenoid biosynthesis by leucoplasts of Citrofortunella mitis. AB - The capacity of leucoplasts to synthesize monoterpene hydrocarbons has been further investigated by studying the synthesis of higher-terpene homologues. Isolated leucoplasts were unable to esterify chlorophyllides into chlorophylls and to synthesize carotenoids. In addition, the later steps of alpha-tocopherol and phylloquinone synthesis were not performed. In spite of the presence of a prenyltransferase activity leading to the synthesis of alcohol terpenes higher than gerniol (farnesol, geranyl-geraniol), these higher terpenes were not further metabolized in vitro by leucoplasts. PMID- 24232852 TI - Fertilization and seed production with pollen from in-vitro-cultured maize tassels. AB - Immature tassel meristems (1-1.5 cm) of maize (Zea mays L.) explanted to a defined nutrient medium underwent further growth and floral development. Microsporogenesis, gametogenesis and pollen maturation were completed within 25 d in vitro. The pollen, recovered from the cultured tassel, germinated on nutrient agar and also on receptive silks. Viable seed produced from controlled pollinations germinated and grew into mature, normal plants. Thus, a significant component of the life cycle of maize can be completed in vitro where analyses and manipulations are possible for both basic and applied research. PMID- 24232853 TI - Association of primary care physicians' exercise habits and their age, specialty, and workplace. AB - BACKGROUND: In this study, we investigated primary care physicians' exercise habits, and the association of this variable with their age, specialty, and workplace. METHODS: The population of this cross-sectional study comprised 3,310 medical doctors who graduated from Jichi Medical University in Japan between 1978 and 2012. The study instrument was a self-administered questionnaire mailed in August 2012 to investigate primary care physicians' exercise habits, age, specialty, and workplace. RESULTS: The 896 available primary care physicians' responses to the self-administered questionnaire were analyzed. Their exercise frequency was as follows: daily, 104 (11.6%); at least 2-3 times per week, 235 (26.2%); no more than once a week, 225 (25.1%); no more than once a month, 278 (31.0%); and other, 52 (5.8%). Their exercise intensity was as follows: high (>=6 Mets), 264 (29.5%); moderate (4-6 Mets), 199 (22.2%); mild, (3-4 Mets), 295 (32.9%); very mild (<3 Mets), 68 (7.6%); none, 64 (7.1%); and other, 6 (0.7%). Their exercise volume was calculated to represent their exercise habits by multiplying score for exercise frequency by score for intensity. Multivariate linear regression analyses showed that the primary care physicians' exercise volumes were associated with their age (P<0.01) and workplace (P<0.01), but not with their specialty (P=0.37). Primary care physicians in the older age group were more likely to have a higher exercise volume than those in the younger age groups (50-60 years > older than 60 years >40-50 years >30-40 years >24-30 years). Primary care physicians working in a clinic were more likely to have a higher exercise volume than those working in a university hospital, polyclinic hospital, or hospital. CONCLUSION: Primary care physicians' exercise habits were associated with their age and workplace, but not with their specialty. PMID- 24232854 TI - Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells. AB - Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1 positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis. PMID- 24232855 TI - Control of dendritic cell trafficking in lymphatics by chemokines. AB - Dendritic cells (DCs) are crucial participants in maintaining immune surveillance of the periphery and initiating primary immune responses within the draining lymph nodes. The afferent lymphatic vessels provide a conduit for this essential trafficking and, as this review will describe, play an active role in regulating DC migration. Afferent lymphatic capillaries support constitutive trafficking of DCs from resting, non-inflamed tissue, to maintain tolerance against self-antigen and to provide immune surveillance. Following exposure to pathogens or pro inflammatory cytokines, DCs mature from phagocytes to professional antigen presenting cells, whilst the lymphatic endothelium adopts an activated phenotype to support the ensuing increase in leukocyte trafficking. The lymphatic endothelial-derived chemokine CCL21 plays a well-characterized role in directing migration of CCR7+ DC in both resting and acute inflammatory conditions. However, efficient trafficking of DCs from inflamed tissue also demands additional chemokine-receptor pairs. Thus, entry of DCs to activated lymphatic vessels is an intricately regulated multi-step process involving numerous chemokines and adhesion molecules. PMID- 24232857 TI - Site and bond-specific dynamics of reactions at the gas-liquid interface. AB - The dynamics of the interfacial reactions of O((3)P) with the hydrocarbon liquids squalane (C30H62, 2,6,10,15,19,23-hexamethyltetracosane) and squalene (C30H50, trans-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene) have been studied experimentally. Laser-induced fluorescence (LIF) was used to detect the nascent gas-phase OH products. The O((3)P) atoms are acutely sensitive to the chemical differences of the squalane and squalene surfaces. The larger exothermicity of abstraction from allylic C-H sites in squalene is reflected in markedly hotter OH rotational and vibrational distributions. There is a more modest increase in translational energy release. A larger fraction of the available energy is deposited in the liquid for squalene than for squalane, consistent with a more extensive geometry change on formation of the allylic radical co-product. Although the dominant reaction mechanism is direct, impulsive scattering, there is some evidence for OH being accommodated at both liquid surfaces, resulting in thermalised translation and rotational distributions. Despite the H-abstraction reaction being strongly favoured energetically for squalene, the yield of OH is substantially lower than for squalane. This is very likely due to competitive addition of O((3)P) to the unsaturated sites in squalene, implying that double bonds are extensively exposed at the liquid surface. PMID- 24232856 TI - Association between variants of the autophagy related gene--IRGM and susceptibility to Crohn's disease and ulcerative colitis: a meta-analysis. AB - BACKGROUND: Polymorphisms in immunity-related GTPase family M (IRGM) gene may be associated with inflammatory bowel disease (IBD) by affecting autophagy. However, the genetic association studies on three common variants in IRGM gene (rs13361189, rs4958847 and rs10065172) have shown inconsistent results. METHODOLOGY/ PRINCIPAL FINDINGS: The PubMed and Embase were searched up to June 5, 2013 for studies on the association between three IRGM polymorphisms and IBD risk. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Finally, we performed a meta-analysis of 25 eligible studies in 3 SNPs located at IRGM gene by using a total of 20590 IBD cases and 27670 controls. The analysis showed modest significant association for the rs13361189, rs4958847 and rs10065172 variants in Crohn's disease (CD): the risk estimates for the allele contrast were OR=1.306 (1.200-1.420), p=5.2 * 10(-10), OR=1.182 (1.082-1.290), p=0.0002, and OR=1.248 (1.057-1.473), p=0.009 respectively (still significant when the p value was Bonferroni adjusted to 0.017). When stratified by ethnicity, significantly increased CD risk was observed in Europeans, but not in Asians. Conversely, there was no association of rs13361189 or rs4958847 variant with risk of ulcerative colitis (UC). CONCLUSIONS/ SIGNIFICANCE: These results indicated that autophagy gene-IRGM polymorphisms appear to confer susceptibility to CD but not UC, especially in Europeans. Our data may provide further understanding of the role of autophagy in the pathogenesis of CD. PMID- 24232858 TI - Saccadic amplitudes during combined saccade-vergence movements result from a weighted average of the target's locations in the two retinas. AB - Recent neurophysiological and behavioral studies have established that the saccadic amplitudes performed during combined saccade-vergence movements are unequal in the two eyes. These studies have not established, however, how the saccadic amplitude of each eye is determined. Our goal here is to fill this lacuna. We use three well-known metric attributes of saccadic movements as constraints and argue that the only quantitative model that obeys these constraints is one where each eye's saccadic amplitude is given by a weighted average of the target's locations in the two retinas. However, this theoretical result does not establish whether the weights in the weighted averaging operation are constant or whether they vary for different targets. To test the simpler of these two possibilities, namely the one of constant weights, we recorded combined saccade-vergence movements performed by human subjects. Our analysis of these movements shows that a constant-weights weighted averaging model provides an excellent description of their saccadic amplitudes. Overall, then, our conclusions are: (1) the two eyes' saccadic amplitudes are determined by weighted averages of the target's locations in the two retinas; (2) for targets within the oculomotor range of natural viewing, which was the range in our experiments, a weighted averaging model that uses constant weights accounts superbly for these saccadic amplitudes. We suggest that the weighted averaging operation that determines saccadic amplitudes is a by-product of a process whose purpose is to yoke the two eyes together. We provide a model explaining how this yoking may be achieved. PMID- 24232859 TI - Passive reading and motor imagery about hand actions and tool-use actions: an fMRI study. AB - Recent studies have shown that motor activations in action verb comprehension can be modulated by task demands (e.g., motor imagery vs. passive reading) and the specificity of action verb meaning. However, how the two factors work together to influence the involvement of the motor system during action verb comprehension is still unclear. To address the issue, the current study investigated the brain activations in motor imagery and passive reading of verbs about hand actions and tool-use actions. Three types of Chinese verbs were used, including hand-action verbs and two types of tool-use verbs emphasizing either the hand or tools information. Results indicated that all three types of verbs elicited common activations in hand motor areas during passive reading and motor imagery. Contrast analyses showed that in the hand verbs and the tool verbs where the hand information was emphasized, motor imagery elicited stronger effects than passive reading in the superior frontal gyrus, supplemental motor area and cingulate cortex that are related to motor control and regulation. For tool-use verbs emphasizing tools information, the motor imagery task elicited stronger activity than passive reading in occipital regions related to visual imagery. These results suggest that motor activations during action verb comprehension can be modulated by task demands and semantic features of action verbs. The sensorimotor simulation during language comprehension is flexible and determined by the interactions between linguistic and extralinguistic contexts. PMID- 24232862 TI - Reply to comments on: "Efficacy of low-level laser therapy in the management of orthodontic pain: a systematic review and meta-analysis" PMID- 24232863 TI - Layer-specific modulation of neuronal excitability by 660-nm laser irradiation in mouse neocortex. AB - It has been reported that laser light irradiation (LLI) could regulate neuronal activities in the forebrain, but little is known if and how LLI in the red wavelength range affects neuronal excitability. Here, we investigated the effects of a continuous diode laser at 660 nm on intrinsic membrane properties and excitability of presumed pyramidal neurons in the thalamocortical input layer (layer 3/4) and in layer 5 of mouse primary auditory cortex using the whole-cell patch-clamp recording technique. In layer 3/4 neurons, 660-nm laser irradiation (LLI-660) at 20 mW for 5 min gradually increased resting membrane potentials, which reached a plateau after irradiation. Concomitantly, LLI-660 decreased onset latency of first action potentials (spikes) without changing spike threshold or peak amplitude, but increased inter-spike interval of initial bursting spike doublets and their peak amplitude ratio. None of these changes was observed in layer 5 neurons. Instead, LLI-660 at 20 mW rapidly reduced spike width ~5 % within 1 min of irradiation onset. The magnitude of this reduction did not change during 5 or 10 min irradiation, and returned quickly to at least baseline levels after turning the LLI off. Decreasing laser power to 10 mW reduced spike width to a lesser extent, suggesting laser power dependence of this phenomenon. These data suggest that LLI-660 regulates different aspects of neuronal excitability in cortical neurons in a layer-dependent manner possibly by affecting different voltage-gated ion channels. PMID- 24232860 TI - The role of different serotonin receptor subtypes in seizure susceptibility. AB - 5-Hydroxytryptamine (5-HT) has the most diverse set of receptors in comparison with any other neurotransmitter or hormone in the body. To date, seven families of 5-HT receptors have been characterized. A great number of studies have been published regarding the role of 5-HT and its receptors in seizures. However, with a few exceptions, the net effect of activating or inhibiting each 5-HT receptor subtype on the development or severity of seizures remains controversial. Additionally, the results of studies, which have used knockout animals to investigate the role of 5-HT receptors in seizures, have sometimes been contradictory to those which have used pharmacological tools. The present study aims to review the available data regarding the influence of each receptor subtype on seizure development and, when possible, reconcile between the apparently different results obtained in these studies. PMID- 24232865 TI - The prognostic value of architectural patterns in a study of 37 type AB thymomas. AB - Spindle cell thymomas with prominent amount of lymphocytes are classified as WHO type AB tumors. However, there are architectural pattern differences in these tumors. We investigated the importance of architectural pattern in type AB thymomas in relation to prognostic value. Archival hematoxylin-eosin stained slides of 37 AB type thymomas were reviewed for the presence (type 1) or absence (type 2) of reticular growth pattern. Reticular growth pattern is defined as the presence of a network of elongated bland spindle cells separating nests of tumor cells admixed with lymphoid cells. The architectural patterns were correlated with tumor stage at diagnosis and presence or absence of recurrent disease. The analysis identified 18 cases of type 1 AB thymoma and 19 cases of type 2. Type 2 cases also had greater cytologic atypia within the spindle cells. Patients with type 1 tumors were more likely to have early stage disease. In contrast, type 2 pattern was associated with higher stage at diagnosis (P<0.001) and greater likelihood for recurrence (P<0.05) and metastases. Architectural features are prognostically relevant in classification of WHO AB type thymomas and may constitute a form of personalized medicine. Independent confirmation of the findings is necessary to confirm the association of architectural pattern with outcomes. PMID- 24232864 TI - Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri. AB - Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a potential role for gamma-herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of known etiology were examined for a series of gamma herpesviruses' DNA/RNA and related proteins using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four proteins known to be in the genome of several gamma-herpesviruses (cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the gamma-herpesviruses, only herpesvirus saimiri expresses all four of these 'pirated' mammalian proteins. We found herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration of the viral nucleic acids or proteins may help diagnose the disease. PMID- 24232866 TI - Cancer testis antigen expression in testicular germ cell tumorigenesis. AB - Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in non-seminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas. PMID- 24232867 TI - Lack of expression of TUBB3 characterizes both BCL2-positive and BCL2-negative follicular lymphoma. AB - Follicular lymphoma is characterized by aberrant BCL2 expression, a feature that is exploited for diagnostic purposes. However, a certain percentage of follicular lymphomas might be BCL2-negative by immunohistochemistry, increasing the difficulties in differentiating them from follicular hyperplasia. The expression of TUBB3 has been recently reported as negative in a small series of follicular lymphomas. We have therefore tested a larger series, including 61 BCL2-positive and 25 BCL2-negative cases, and compared them with 61 reactive lymphoid tissues. First, a subjective score of TUBB3 staining was applied, showing that it was consistently positive in reactive germinal centers, while most follicular lymphomas were negative; in fact, only 10/61 (16%) BCL2-positive and 1/25 (4%) BCL2-negative cases showed a positive staining for TUBB3, while 58/61 (95%) of tissues with follicular hyperplasia were positive. The application of a standardized scoring system to a large number of follicles, based on virtual slides, demonstrated that reactive lymphoid tissues had a significantly higher number of TUBB3-positive follicles both compared with BCL2-positive cases and to BCL2-negative cases. Our data support the use of TUBB3 staining in differentiating follicular lymphoma, including BCL2-negative cases, from follicular hyperplasia. PMID- 24232868 TI - [Rhinorrhea following laryngectomy : Treatment with botulinum toxin type A.] AB - After laryngectomy, the transport of intranasal secretions is often inadequate due to the lack of the nasal ventilation. Consequently, persistent and disruptive anterior rhinorrhea may occur. We report the case of a 61-year-old man who had recently undergone a laryngectomy and who was successfully treated with bilateral injections of botulinum toxin into the anterior portion of the inferior turbinates. After treatment, rhinorrhea was clearly reduced. Therefore, symptomatic treatment of anterior rhinorrhea with local injections of botulinum toxin type A should be considered as an option to improve the quality of life in laryngectomized patients. PMID- 24232869 TI - Implementation and performance evaluation of simultaneous PET/MR whole-body imaging with continuous table motion. AB - In current PET/MR systems, the data acquisition paradigm is based on a multistation examination, imaging the patient from hip to head. This strategy has potential limitations, especially in terms of workflow and PET acquisition efficiency. In this work, the technical implementation of simultaneous PET and MR data acquisition with continuous table motion (CTM) is presented. PET and MR data acquired with CTM are evaluated in terms of image quality with respect to table motion speed. METHODS: Phantom, volunteer, and patient data were acquired on an integrated whole-body PET/MR system. Phantom experiments were used to systematically quantify image quality parameters including signal-to-noise ratio, geometric distortions, and artifacts in PET and MR scans as a function of different table speeds. Volunteer scans (n = 4) allowed evaluation of CTM MR protocols in a realistic setting, and patient scans (n = 3) were obtained to validate the technique in a clinical workflow. RESULTS: In phantoms, PET image quality, signal-to-noise ratio, geometry, and artifact behavior were found not to be influenced by continuous table motion over the evaluated table motion speeds from 0.8 to 4.6 mm/s. This also holds true for PET patient data where acquisitions were performed with varying table speeds of up to 46 mm/s. For MR, in most scans image quality of CTM scans was found to be comparable to the identical sequence acquired in multistation mode; however, some sequence features (e.g., signal intensity normalization) with impact on MR contrast are currently missing for CTM MR sequences. CONCLUSION: Data acquisition with continuous table motion in the PET/MR versus multistation acquisition scheme provides data of comparable quality in both PET and MR. This new acquisition paradigm potentially can provide a higher flexibility in simultaneous PET and MR whole-body data acquisition and facilitate examination planning and PET/MR hybrid imaging workflow. PMID- 24232870 TI - Advanced imaging of cardiac sarcoidosis. AB - Sarcoidosis is a systemic granulomatous disease of unknown etiology. Cardiac involvement may occur, leading to an adverse outcome. Although early treatment to improve morbidity and mortality is desirable, sensitive and accurate detection of cardiac sarcoidosis remains a challenge. Accordingly, interest in the use of advanced imaging such as cardiac MR and PET with (18)F-FDG is increasing in order to refine the clinical workup. Although the field is still facing challenges and uncertainties, this article presents a summary of clinical background and the current state of diagnostic modalities and treatment of cardiac sarcoidosis. PMID- 24232872 TI - Helicoidal cell-wall texture in root hairs. AB - It is shown that root hairs of most aquatic plants have a helicoidal cell-wall texture. Cell walls of root hairs of the aquatic/marshland plant Ranunculus lingua, however, have an axial microfibril alignment. The occurrence of a helicoidal wall texture is not limited to root hairs of aquatic plants: the terrestrial plant Zebrina purpusii has a helicoidal root-hair wall texture, too. With the exception of the grasses, the occurrence of root hairs with helicoidal cell walls pertains to species with predetermined root-hair-forming cells, trichoblasts. The rotation mode of the helicoid is species-specific. The average angle between fibrils of adjacent lamellae varies from 23 degrees to 40 degrees . In Hydrocharis morsus-ranae, cortical microtubules have a net-axial orientation and thus do not parallel nascent microfibrils. The deposition of the helicoidal cell wall is discussed. PMID- 24232871 TI - (18)F-alfatide II and (18)F-FDG dual-tracer dynamic PET for parametric, early prediction of tumor response to therapy. AB - A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with (18)F-alfatide II ((18)F-AlF-NOTA-E[PEG4 c(RGDfk)]2) and (18)F-FDG for parametric monitoring of tumor responses to therapy. METHODS: We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with (18)F-alfatide II, followed 40 min later by (18)F-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of (18)F-alfatide II for the 40 min before (18)F-FDG injection and then extrapolated to 90 min. The (18)F-FDG tumor time-activity curve was isolated from the 90-min dual-tracer tumor time-activity curve by subtracting the fitted (18)F-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the (18)F-alfatide II binding potential (Bp = k3/k4) and volume of distribution (VD) and (18)F-FDG influx rate ((K1 * k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. RESULTS: The transport and binding rate parameters K1-k3 of (18)F alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single tracer scan (R(2) > 0.95). Compared with the results of single-tracer PET imaging, (18)F-FDG tumor uptake and influx were recovered well from dual-tracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of (18)F-alfatide II or (18)F-FDG were observed, both (18)F alfatide II Bp and (18)F-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein bound particles, a significant decrease was observed only with (18)F-alfatide II Bp value from kinetic analysis but not (18)F-FDG influx. CONCLUSION: The parameters fitted with compartmental modeling from the dual-tracer dynamic imaging are consistent with those from single-tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 d after doxorubicin treatment started, at day 3 there were already substantial differences in (18)F-alfatide II Bp and (18)F-FDG influx rate. Dual-tracer imaging can measure (18)F-alfatide II Bp value and (18)F-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomic changes, and thus parametric imaging may offer the promise of early prediction of therapy response. PMID- 24232873 TI - Immunological assay of phytochrome in small sections of roots and other organs of maize (Zea mays L.) seedlings. AB - Phytochrome was determined in small sections of maize (Zea mays L.) seedlings by means of a highly specific double sandwich enzyme immunoassay which uses a monoclonal anti-phytochrome antibody for binding phytochrome and anti-phytochrome serum to detect the bound phytochrome. The distribution of phytochrome in maize seedlings was followed from germination to the 7th d after soaking the caryopses. Regions of high phytochrome accumulation were found in the coleoptile tip, the root cap and the shoot apex: the values for 5-d-old seedlings were 120, 80 and 70 MUg phytochrome per g fresh weight (or 0.91, 0.61 and 0.53 nmol.g(-1)), respectively. The mesocotyl and the leaves contained relatively low amounts of phytochrome (less than 10 MUg.g(-1)FW), which were almost uniformly distributed throughout these organs. As might be expected, regions of these organs adjacent to the shoot apex showed higher levels. The root, other than root tip, was almost devoid of phytochrome (0.2 to 0.5 MUg.g(-1)). The general distribution of phytochrome in organs did not change during the development of seedlings. The amount of phytochrome, however, did fluctuate: up to the 5th or 6th d after soaking the caryopses, the levels increased in the regions of high phytochrome accumulation but thereafter decreased. After the 6th d the roots were 15 cm or longer and the coleoptiles became prone to penetration by primary leaves. The tips of adventitious roots, emerging after the 6th d, were also found to contain phytochrome. When the root cap was illuminated (4.3 W.m(-1)), phytochrome was degraded as in illuminated shoots. Degradation of phytochrome in coleoptile, mesocotyl and shoot apex started with a lag phase but phytochrome degradation in the root cap and the leaves started without a lag. In contrast to shoot phytochrome, which was almost completely degraded under continuous illumination, about 3% of initial phytochrome was measured in root caps after 24 h continuous illumination. Some of the data, obtained by immunological measurements, may indicate differences between phytochrome, or its synthesis or degradation, in the root cap and shoots. The results are discussed with a view to different red-light mediated responses of grass seedlings. PMID- 24232874 TI - Changes in the pattern of phospholipid synthesis during the induction by cytokinin of cell division in soybean suspension cultures. AB - A method is described for preparing fully viable, cytokinin-starved soybean (Glycine max (L.) Merr. cv. Acme) cells from a suspension-culture of callus tissue. The cells respond to kinetin treatment by re-initiating cell division. We present evidence, from the pattern of incorporation of (32)P-labelled inorganic phosphate into individual phospholipids during the first hour of this response, that the synthesis of phosphatidylinositol (PI) and of phosphatidic-acid head groups is affected within 15 min. The polyphosphoinositide phosphatidylinositol 4 phosphate, but not phosphatidylinositol 4,5-bisphosphate, was detected in the tissue. The characteristics of cytokinin-induced PI synthesis in cytokinin starved soybean cells appear to resemble the 'PI response' of animal cells. PMID- 24232875 TI - Cooperation of epidermis and inner tissues in auxin-mediated growth of maize coleoptiles. AB - The function of the epidermis in auxinmediated elongation growth of maize (Zea mays L.) coleoptile segments was investigated. The following results were obtained: i) In the intact organ, there is a strong tissue tension produced by the expanding force of the inner tissues which is balanced by the contracting force of the outer epidermal wall. The compression imposed by the stretched outer epidermal wall upon the inner tissues gives rise to a wall-pressure difference which can be transformed into a water-potential difference between inner tissues and external medium (water) by removal of the outer epidermal wall. ii) Peeled segments fail to respond to auxin with normal growth. The plastic extensibility of the inner-tissue cell walls (measured with a constant-load extensiometer using living segments) is not influenced by auxin (or abscisic acid) in peeled or nonpeeled segments. It is concluded that auxin induces (and abscisic acid inhibits) elongation of the intact segment by increasing (decreasing) the extensibility specifically in the outer epidermal wall. In addition, tissue tension (and therewith the pressure acting on the outer epidermal wall) is maintained at a constant level over several hours of auxin-mediated growth, indicating that the inner cells also contribute actively to organ elongation. However, this contribution does not involve an increase of cell-wall extensibility, but a continuous shifting of the potential extension threshold (i.e., the length to which the inner tissues would extend by water uptake after peeling) ahead of the actual segment length. Thus, steady growth involves the coordinated action of wall loosening in the epidermis and regeneration of tissue tension by the inner tissues. iii) Electron micrographs show the accumulation of striking osmiophilic material (particles of approx. 0.3 MUm diameter) specifically at the plasma membrane/cell-wall interface of the outer epidermal wall of auxin-treated segments. iv) Peeled segments fail to respond to auxin with proton excretion. This is in contrast to fusicoccin-induced proton excretion and growth which can also be readily demonstrated in the absence of the epidermis. However, peeled and nonpeeled segments show the same sensitivity to protons with regard to the induction of acid-mediated in-vivo elongation and cell-wall extensibility. The observed threshold at pH 4.5-5.0 is too low to be compatible with a 'second messenger' function of protons also in the growth response of the inner tissues. Organ growth is described in terms of a physical model which takes into account tissue tension and extensibility of the outer epidermal wall as the decisive growth parameters. This model states that the wall pressure increment, produced by tissue tension in the outer epidermal wall, rather than the pressure acting on the inner-tissue walls, is the driving force of growth. PMID- 24232876 TI - Rates of glycolate synthesis and metabolism during photosynthesis of Euglena and microalgae grown on low CO2. AB - The rate of glycolate excretion in Euglena gracilis Z and some microalgae grown at the atmospheric level of CO2 was determined using amino-oxyacetate (AOA). The extracellular O2 concentration was kept at 240 MUM by bubbling the incubation medium with air. Glycolate, the main excretion product, was excreted by Euglena at 6 MUmol.h(-1).(mg chlorophyll (Chl))(-1). Excretion depended on the presence of AOA, and was saturated at 1 mM AOA. A substituted oxime formed from glyoxylate and AOA was also excreted. Bicarbonate added at 0.1 mM did not prevent the excretion of glycolate. The excretion of glycolate increased with higher O2 concentrations in the medium, and was competitively inhibited by much higher concentrations of bicarbonate. Aminooxyacetate also caused excretion of glycolate from the green algae, Chlorella pyrenoidosa, Scenedesmus obliquus and Chlamydomonas reinhardtii grown on air, at the rates of 2-7 MUmol.h(-1).(mg Chl)( 1) in the presence of 0.2-0.6 mM dissolved inorganic carbon, but the cyanobacterium, Anacystis nidulans, grown in the same way did not excrete glycolate. The efficiency of the CO2-concentrating mechanism to suppress glycolate formation is discussed on the basis of the magnitude of glycolate formation in these low-CO2-grown cells. PMID- 24232877 TI - The physiological role of lipoxygenase in ethylene formation from 1 aminocyclopropane-1-carboxylic acid in oat leaves. AB - In order to understand the physiological significance of the in-vitro lipoxygenase (EC 1.13.11.12)-mediated ethylene-forming system (J.F. Bousquet and K.V. Thimann 1984, Proc. Natl. Acad. Sci. USA 81, 1724-1727), its characteristics were compared to those of an in-vivo ethylene-forming system. While oat (Avena sativa L.) leaves, as other plant tissues, preferentially converted only one of the 1-amino-2-ethylcyclopropane-1-carboxylic acid (AEC) isomers to 1-butene, the lipoxygenase system converted all four AEC isomers to 1-butene with nearly equal efficiencies. While the in-vivo ethylene-forming system of oat leaves was saturable with ACC with a Km of 16 MUM, the lipoxygenase system was not saturated with ACC even at 10 mM. In contrast to the in-vivo results, only 10% of the ACC consumed in the lipoxygenase system was converted to ethylene, indicating that the reaction is not specific for ethylene formation. Increased ACC-dependent ethylene production in oat leaves following pretreatment with linoleic acid has been inferred as evidence of the involvement of lipoxygenase in ethylene production. We found that pretreating oat leaves with linoleic acid resulted in increased ACC uptake and thereby increased ethylene production. A similar effect was observed with oleic acid, which is not a substrate of lipoxygenase. Since linoleic acid hydroperoxide can substitute for lipoxygenase and linoleic acid in this system, it is assumed that the alkoxy radicals generated during the decomposion of linoleic acid hydroperoxide are responsible for the degradation of ACC to ethylene. Our results collectively indicate that the reported lipoxygenase system is not the in-vivo ethylene-forming enzyme. PMID- 24232878 TI - Coordinate control of sucrose formation in soybean leaves by sucrose-phosphate synthase and fructose-2,6-bisphosphate. AB - Net photosynthesis (CER), assimilate-export rate, sucrose-phosphate-synthase (EC 2.4.1.14) activity, fructose-2,6-bisphosphate content, and 6-phosphofructo-2 kinase (EC 2.7.1.105) activity were monitored in leaves of soybean (Glycine max (L.) Merr.) plants during a 12:12 h day-night cycle, and in plants transferred, at regular intervals throughout the diurnal cycle, to an illuminated chamber for 3 h. In the control plants, assimilate-export rate decreased progressively during the day whereas in transferred plants, a strongly rhythmic fluctuation in both CER and export rate was observed over the 24-h test period. Two maxima during the 24-h period for both processes were observed: one when plants were transferred during the middle of the normal light period, and a second when plants were transferred during the middle of the normal dark period. Overall, the results indicated that export rate was correlated positively with photosynthetic rate and sucrose-phosphate-synthase activity, and correlated negatively with fructose-2,6 bisphosphate levels, and that coarse control and fine control of the sucrose formation pathway are coordinated during the diurnal cycle. Diurnal changes in sucrose-phosphate-synthase activity were not associated with changes in regulatory properties (phosphate inhibition) or substrate affinities. The biochemical basis for the diurnal rhythm in sucrose-phosphate-synthase activity in the soybean leaf thus appears to involve changes in the amount of the enzyme or a post-translational modification that affects only the maximum velocity. PMID- 24232879 TI - Role of nitrogen in the photoinduction of protoperithecia and carotenoids in Neurospora crassa. AB - Nitrogen, as KNO3 or NH4NO3, can inhibit the photoinduction of protoperithecia in Neurospora crassa when present in the medium at a high concentration but does not inhibit the photoinduction of carotenoids. The point at which the presence of high nitrogen levels is no longer inhibitory is 5 h after illumination. PMID- 24232880 TI - Gene expression in the soybean seed axis during germination and early seedling growth. AB - Copy-DNA clones have been obtained that distinguish eight messenger mRNAs, moderately abundant in the axes of the germinating soybean (Glycine max (L.) Merr.) seedling. These clones have been used to characterize the size of the mRNAs and to anlyze the accumulation of the mRNAs at different time points and in different parts of the axis during germination and early seedling growth. Three of the mRNAs accumulate to a substantial level by 9 h, a time point before either the beginning of growth or the accumulation of polyribosomes. Four other mRNAs reach a substantial level only at 24 h, a period when rapid seedling growth is occurring. Those mRNAs whose accumulation begins at 24 h were found only in the top (hypocotyl) half of the 24-h seedlings, while the remaining mRNAs were present also in the bottom half of the seedlings in different amounts. By 44 h, the bottom 0.5 cm of the seedlings, i.e., the region of meristematic growth, had little or none of the mRNAs, with the exception of one mRNA. These temporal and spatial observations indicate that many of the mRNAs are not involved simply in the general maintenance of ongoing cell proliferation, but that they may be related to differentiation during early seedling formation. Further, the early accumulating mRNAs may be functioning in regulating the onset of seedling growth. PMID- 24232881 TI - Transport and processing of the glycosylated precursor of Concanavalin A in jack bean. AB - Concanavalin A (ConA) is a tetrameric lectin which is synthesized in the developing cotyledons of jack bean (Canavalia ensiformis L.) as a glycosylated precursor, pro-concanavalin A (pro-ConA). The processing of pro-ConA involves the excision of a small glycopeptide from the center of the pro-ConA molecule, and the ligation of the two polypeptides. In this paper, we show that pro-ConA is associated with the endoplasmic reticulum/Golgi fraction of the cells, and that the processing of pro-ConA occurs in the protein bodies. Processing is a complex process and different intermediate-sized polypeptides appear at different times during cotyledon development. The ConA-related polypeptides which accumulate during seed development may be the products of alternate processing events or breakdown products of ConA, rather than precursors of ConA. When glycosylation is prevented by tunicamycin, there is very little transport of pro-ConA out of the endoplasmic reticulum/Golgi system to the protein bodies; the unglycosylated pro ConA which is transported is slowly processed. Tunicamycin does not prevent the transport of canavalin (a protein which is not glycosylated) or the transport and processing of the small amounts of glycosylated pro-ConA synthesized in the presence of the drug. This is, to our knowledge, the first demonstration that the transport of a glycoprotein in plant cells is dependent on the presence of the glycan. PMID- 24232882 TI - Basic peroxidases in isolated vacuoles of nicotiana tabacum L. AB - Vacuoles of tobacco mesophyll and of suspension-cultured cells were isolated in order to study the localization of peroxidase isoenzymes. Only basic peroxidases were detectable by electrophoretic separation of the vacuolar sap. Some of the basic peroxidases have formerly been described as an ionically bound cell-wall fraction. This fraction, however, was found to be an artifact produced by incomplete cell breakage. Reinvestigation of isolated cell walls confirmed that mainly acidic peroxidases are localized in the cell walls where they move freely or are bound. As a consequence of former and present results we think it probable that all of the peroxidase isoenzymes are secretory proteins because they have to be transported from the sites of synthesis in the cytoplasm to the sites of function, the extracytoplasmic spaces, cell wall (acidic peroxidases), and vacuole (basic peroxidases). PMID- 24232884 TI - Redistribution of potassium, chloride and calcium during the gravitropically induced movement of Mimosa pudica pulvinus. AB - When the leaves of Mimosa pudica are changed from their normal position in the gravitational field, they perform reversible compensatory movements by means of pulvini. These movements are not the result of growth processes but involve reversible turgor variations. These variation are concomitant with ion migrations within pulvini: during the gravitropic movement, K(+) and Cl(-) shift towards the adaxial half of the motor organ whereas Ca(2+) shifts towards the abaxial half. Compounds known to affect K(+) transport, tetraethylammonium chloride and valinomycin, do not hinder the gravitropic movement but inhibit strongly the seismonastic reaction. The same general result is obtained with compounds affecting anion transport, disulfonic stilbenes and 9-anthracene carboxylic acid. Calcium chelators inhibit the gravitropic movement more efficiently than the seismonastic reaction and the calcium ionophore A 23 187 increases both movements. The data obtained with these various compounds indicate that ions do not have the same functional importance in the regulation of the two different pulvinar movements. PMID- 24232883 TI - Resistance of Rosa microtubule polymerization to colchicine results from a low affinity interaction of colchicine and tubulin. AB - The inhibition of the polymerization of tubulin from cultured cells of rose (Rosa. sp. cv. Paul's scarlet) by colchicine and the binding of colchicine to tubulin were examined in vitro and compared with data obtained in parallel experiments with bovine brain tubulin. Turbidimetric measurements of taxol induced polymerization of rose microtubules were found to be sensitive and semiquantitative at low tubulin concentrations, and to conform to some of the characteristics of a nucleation and condensation-polymerization mechanism for assembly of filamentous helical polymers. Colchicine inhibited the rapid phase of polymerization at 24 degrees C with an apparent inhibition constant (K i) of 1.4.10(-4) M for rose tubulin and an apparent K i=8.8.10(-7) M for brain tubulin. The binding of [(3)H]colchicine to rose tubulin to form tubulin-colchicine complex was mildly temperature-dependent and slow, taking 2-3 h to reach equilibrium at 24 degrees C, and was not affected by vinblastine sulfate. The binding of [(3)H]colchicine to rose tubulin was saturable and Scatchard analysis indicated a single class of low-affinity binding sites having an apparent affinity constant (K) of 9.7.10(2) M(-1) and an estimated molar binding stoichiometry (r) of 0.47 at 24 degrees C. The values for brain tubulin were K=2.46.10(6) M(-1) and r=0.45 at 37 degrees C. The binding of [(3)H]colchicine to rose tubulin was inhibited by excess unlabeled colchicine, but not by podophyllotoxin or tropolone. The data demonstrate divergence of the colchicine binding sites on plant and animal tubulins and indicate that the relative resistance of plant microtubule polymerization to colchicine results from a low affinity interaction of colchicine and tubulin. PMID- 24232885 TI - Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity. AB - The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev.min( 1). These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1.g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1.g follows the wellestablished pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels. PMID- 24232886 TI - The effect of abscisic acid on cell turgor pressures, solute content and growth of wheat roots. AB - Abscisic acid (ABA) was shown to influence turgor pressure and growth in wheat (Triticum aestivum L.) roots. At a concentrations of 25 mmol.m(-3), ABA increased the turgor pressure of cells located within 1 cm of the tip by up to 450 kPa. At 4 to 5 cm from the root tip this concentration of ABA reduced the turgor pressure of peripheral cells (epidermis and the first few cortical cell layers) to zero or close to zero while that of the inner cells was increased. Increases in sap osmolality were dependent on the concentration of ABA and the effect saturated at 5 mmol.m(-3) ABA. The increase in osmolality took about 4 h and was partly the result of reducing-sugar accumulation. Levels of inorganic cations were not affected by ABA. Root growth was inhibited at ABA concentrations that caused a turgor-pressure increase. The results show that while ABA can affect root cell turgor pressures, this effect does not result in increased root growth. PMID- 24232887 TI - Isolation and identification of proteins from the peptide-transport carrier in the scutellum of germinating barley (Hordeum vulgare L.) embryos. AB - Peptide-transport proteins, intrinsic to the epithelial plasmalemmae of the scutella of germinating barley (Hordeum vulgare L.) embryos, have been selectively labelled with p-chloro-[(203)Hg]mercuribenzenesulphonate using both a substrate-screening technique and a procedure developed to label exclusively vicinal dithiol groups, which were shown previously (Walker-Smith and Payne, 1983, FEBS Lett. 160, 25-30) to be essential components of the peptide-transport system. After radioactive labelling, proteins from the scutellar membranes have been solubilised with lithium diiodosalicylate plus sodium dodecyl sulphate and separated by using polyacrylamide gel electrophoresis. Fluorography and silver staining of these gels has for the first time allowed identification of two presumptive components of the peptide-transport system. These components only become detectable in an extract of the scutellar epithelia after 15 h imbibition, concomitant with a dramatic increase in peptide-transport activity, and they remain present at least 3 d after the onset of germination. [(35)] Methionine was shown to be incorporated into these proteins between 15-20 h after imbibition, but its incorporation during a similar 5 h period into scutella isolated after 3 d was undetectable, implying a slow turnover of these proteins during the later stages of germination. PMID- 24232888 TI - Electrical characteristics of stomatal guard cells: The ionic basis of the membrane potential and the consequence of potassium chlorides leakage from microelectrodes. AB - The membrane electrical characteristics of stomatal guard cells in epidermal strips from Vicia faba L. and Commelina communis L. were explored using conventional electrophysiological methods, but with double-barrelled microelectrodes containing dilute electrolyte solutions. When electrodes were filled with the customary 1-3 M KCl solutions, membrane potentials and resistances were low, typically decaying over 2-5 min to near-30 mV and <0.2 komega.cm(2) in cells bathed in 0.1 mM KCl and 1 mM Ca(2+), pH 7.4. By contrast, cells impaled with electrodes containing 50 or 200 mM K(+)-acetate gave values of 182+/-7 mV and 16+/-2 komega.cm(2) (input resistances 0.8-3.1 Gomega, n=54). Potentials as high as (-) 282 mV (inside negative) were recorded, and impalement were held for up to 2 h without appreciable decline in either membrane parameter. Comparison of results obtained with several electrolytes indicated that Cl(-) leakage from the microelectrode was primarily responsible for the decline in potential and resistance recorded with the molar KCl electrolytes. Guard cells loaded with salt from the electrodes also acquired marked potential and conductance responses to external Ca(2+), which are tentatively ascribed to a K(+) conductance (channel) at the guard cell plasma membrane.Measurements using dilute K(+)-acetate-filled electrodes revealed, in the guard cells, electrical properties common to plant and fungal cell membranes. The cells showed a high selectivity for K(+) over Na(+) (permeability ratio PNa/PK=0.006) and a near Nernstian potential response to external pH over the range 4.5-7.4 (apparent PH/PK=500-600). Little response to external Ca(2+) was observed, and the cells were virtually insensitive to CO2. These results are discussed in the context of primary, charge-carrying transport at the guard cell plasma membrane, and with reference to possible mechanisms for K(+) transport during stomatal movements. They discount previous notions of Ca(2+)-and CO2-mediated transport control. It is argued, also, that passive (diffusional) mechanisms are unlikely to contribute to K(+) uptake during stomatal opening, despite membrane potentials which, under certain, well-defined conditions, lie negative of the potassium equilibrium potential likely prevailing. PMID- 24232889 TI - Comparison between responses to gametophytic and sporophytic recurrent selection in maize (Zea mays L.). AB - In order to evaluate the response at both the gametophytic and sporophytic level of a selection based on the pollen competitive ability and to compare its effects with those obtainable from a conventional sporophytic procedure, three recurrent selection plans were developed in maize starting from the same F2 population. Two gametophytic recurrent selection procedures at high (GSH) and low (GSL) selection intensity were performed by utilizing, to advance the populations, kernels taken from the base (GSH) or apex (GSL) of ears obtained from pair-crosses of randomly chosen plants. The third scheme was a sporophytic full-sib recurrent selection procedure (SS); the only selection criterion was the machine-harvestable grain yield of the families. In a sixyear period of selection, six cycles of both GSH and GSL and three cycles of SS were performed. The source and the selected populations (16 entries) were tested for pollen performance and for sporophytic traits. The selection cycles advanced through GSH showed a progressive increase, as compared to GSL, in pollen tube length measured at 4 h of in vitro culture. The SS cycles response was intermediate at 4 h whereas at 2 h it exceeded both GSH and GSL. A slight decrease in pollen diameter was evidenced in populations advanced with GSL procedure. The SS selection caused a marked increase for grain yield, lateness, leaves per plant and plant height. No response was shown by gametophytic selection for grain yield. The GSH procedure, however, led to an increase in kernel weight and to a decrease in kernel moisture, leaf number and plant height, as compared to GSL. Though gametophytic selection showed limited effects on sporophytic traits, it can be considered an efficient tool to supplement conventional sporophytic selection. PMID- 24232890 TI - Distribution of restriction site polymorphism within the chloroplast genome of the genus Glycine, subgenus Soja. AB - Restriction fragment length polymorphisms (RFLPs) have been used to detect intragenic sequence diversity in Glycine subgenus soja chloroplast DNA. The distribution of these RFLPs allow Glycine max and G. soja accessions to be grouped according to cytoplasmic genetic relatedness. DNA clones from mung bean chloroplast DNA were used to locate the RFLPs to specific regions of the chloroplast genome. In the course of the experiments, several previously unobserved RFLPs were also identified. At least six molecular changes were detected, including both restriction site loss or gain and insertion/deletion events. Three of the fragment polymorphisms detected are due to changes in the juncture region between one inverted repeat region and the large single-copy region. Probes detecting polymorphisms in three representative soybean genotypes were used to screen additional cultivars and Plant Introductions. The distribution of RFLP patterns in these accessions were consistent with the patterns of previously described cytoplasmic groupings, with the exception of one accession, which formed a new plastome group. PMID- 24232891 TI - Assessing three methods for identification of desirable genotypes in white cabbage (Brassica oleracea L. var. capitata). AB - A desirable genotype is a genotype performing well in a chosen set of environments. Three methods for identification of desirable genotypes were assessed in two cabbage data sets: regression analysis, multidimensional scaling of dissimilarity matrices, and biplot of deviation matrices. Using the regression approach is not recommended mainly for two reasons: (1) it is difficult to identify the desirable genotypes since one has to unify three parameters into one decision; (2) the regression method failed to identify the most desirable genotypes in one of the data sets. Multidimensional scaling and the biplot method were in accordance with each other and with the mean tables when different subsets where compared. Consequently, they were considered more adequate for identifying desirable genotypes. In cases where rank 2 approximation of the analysed matrix was justified, the biplot revealed more information in one display and was, therefore, considered particularly useful in plant breeding for larger target areas. PMID- 24232892 TI - Restriction fragment length polymorphism diversity in soybean. AB - Fifty-eight soybean accessions from the genus Glycine, subgenus Soja, were surveyed with 17 restriction fragment length polymorphism (RFLP) genetic markers to assess the level of molecular diversity and to evaluate the usefulness of previously identified RFLP markers. In general, only low levels of molecular diversity were observed: 2 of the 17 markers exhibited three alleles per locus, whereas all others had only two alleles. Thirty-five percent of the markers had rare alleles present in only 1 or 2 of the 58 accessions. Molecular diversity was least among cultivated soybeans and greatest between accessions of different soybean species such as Glycine max (L.) Merr. and G. soja Sieb. and Zucc. Principal component analysis was useful in reducing the multidimensional genotype data set and identifying genetic relationships. PMID- 24232893 TI - DNA polymorphism in Allium cepa cytoplasms and its implications concerning the origin of onions. AB - Mitochondrial and chloroplast DNA was isolated from fertile and cytoplasmic male sterile cultivars of cultivated onions. Restriction fragment length polymorphism led to the distinction between cytoplasms S and M. Mitochondrial DNA patterns from S cytoplasms appeared dentical and characterized mostly male sterile lines. An open-pollinated variety was found to bear this cytoplasm and thought to be the origin of S types. Mitochondrial DNA patterns from M cytoplasms were subdivided into four types, M1 and M2 corresponding to normal N cytoplasm, M3 and M4 probably corresponding to T cytoplasms. S and M cytoplasms were also distinguished by chloroplast DNA restriction patterns. Our results confirm previous genetic distinction between S, N and T cytoplasms. PMID- 24232894 TI - Production and evaluation of a synthetic hexaploid in blueberry. AB - One synthetic hexaploid clone (Hex-DT) was produced by placing 3-node stem cuttings of triploid blueberry clone FL 81-19 [V. corymbosum (4x) x V. elliottii (2x)] on blueberry micropropagation medium supplemented with 0.6% agar, 24.6 MUM 2ip, and 0.02% colchicine. The most effective chromosome-doubling was achieved with colchicine over 6 days, for 6 h per day. Pollen stainability and pollen germination in the hexaploid Hex-DT were 42.2% and 13.0%, respectively, versus 87.9% and 50.9% in Hex-F1, a hexaploid F1 hybrid between V. ashei (6x) x FL 81-19 (3x). The number of seedlings produced per flower pollinated with V. ashei pollen in Hex-F1 was similar to the number obtained from V. ashei x V. ashei crosses, and at least twice the number produced by Hex-DT pollinated with V. ashei pollen. Observed mean numbers of univalents, bivalents, trivalents, quadrivalents, and hexavalents per PMC at metaphase I in Hex-DT were 1.29, 20.30, 2.31, 2.63, and 2.11, respectively. No univalents were observed in Hex-F 1, but the mean frequencies of bivalents, trivalents, quadrivalents, and hexavalents were 29.14, 0.87, 1.91, and 0.58, respectively. Irregularities such as chromosome lagging and unequal disjunction were observed at both anaphase I and II in Hex-DT. Anaphases I and II in Hex-F1 were normal with few irregularities. The high fertility observed in Hex-F1 suggests a high level of homology among the three species contributing to its makeup. PMID- 24232895 TI - Inheritance and mapping of seed lipoxygenase polypeptides in Pisum. AB - Analysis of crosses of Pisum lines showing variation in the apparent molecular weight of seed lipoxygenase polypeptides indicates that the genes encoding the two major pea seed lipoxygenase polypeptides are closely linked. The lipoxygenase locus, designated Lox, maps to a position on linkage group 4 between Np and le. PMID- 24232896 TI - Is Nor region variability in wheat invariably caused by tissue culture? AB - In a previous study we observed extensive Nor region variability in tissue culture derived plants of only one out of three tested wheat cultivars. This finding prompted us to further question whether or not this variability was invariably caused by in vitro culture. In the present study, the upper halves of spikes from four source plants of the inbred cultivar 'ND7532' were removed 12 days after anthesis. The immature embryos from these halves were cultured and regenerated into plants. The lower halves of the same spikes were retained on the plants to obtain mature caryopses. DNA was extracted from seedlings, cut with TaqI endonuclease, run on agarose gels, and the respective Southern blots were probed with the plasmid pTA71 to reveal the Nor region patterns. The sexual progeny of regenerants from three out of four source plants derived from the immature embryos provided Nor region patterns which were exactly identical to the patterns obtained from seedlings which germinated from the caryopses matured on the respective source spikes. The regenerants from the fourth source plant provided variable Nor region patterns. Analyses of the Nor region patterns of 21 individual seedlings germinated from caryopses of this source plant showed that 18 had a three-fragment pattern (consisting of 3.0, 2.7 and 1.9 kb fragments) while three seedlings lacked one (2.7 of 1.9 kb) fragment. Furthermore, the next sexual progeny of the regenerants which had a three-fragment pattern further segregated into three- and two-fragment patterns.These results, in conjunction with previous reports on Nor region variability among tissue-culture derived plants, suggest that this variability is not invariably related to in vitro culture. PMID- 24232897 TI - Detection of linkage between quantitative trait loci and restriction fragment length polymorphisms using inbred lines. AB - In segregating populations, large numbers of individuals are needed to detect linkage between markers, such as restriction fragment length polymorphisms (RFLPs), and quantitative trait loci (QTL), limiting the potential use of such markers for detecting linkage. Fewer individuals from inbred lines are needed to detect linkage. Simulation data were used to test the utility of two methods to detect linkage: maximum likelihood and comparison of marker genotype means. When there is tight linkage, the two methods have similar power, but when there is loose linkage, maximum likelihood is much more powerful. Once inbred lines have been established, they can be screened rapidly to detect QTL for several traits simultaneously. If there is sufficient coverage of the genome with RFLPs, several QTL for each trait may be detected. PMID- 24232898 TI - Artificial seeds in barley: encapsulation of microspore-derived embryos. AB - An in vitro culture system has been developed for barley (Hordeum vulgare), which yields high frequencies of high quality microspore-derived embryos without an intervening callus phase. The embryos are very similar to zygotic embryos with regard to their morphology and germination capacity. These embryos were encapsulated in sodium alginate to produce individual beads containing one embryo each. In accordance with the literature, these beads are denoted "artificial seeds". The artificial seeds germinated well and with a root system superior to that of non-encapsulated embryos. The artificial seeds also maintained their germination capacity for at least 6 months, whereas non-encapsulated embryos did not survive more than 2 weeks in storage. Artificial seeds, thus, probably provide a simple and universal delivery system of in vitro plantlets to greenhouse or field. PMID- 24232899 TI - Deployment to plantations of numbers and proportions of clones with special emphasis on maximizing gain at a constant diversity. AB - The value of a mixture of genetic entries present in different proportions is defined. A measure of the disadvantage of reduced diversity is defined as the sum of the squares of the proportions of the different entries. An algorithm for maximizing genetic gain of the mixture under the constraint of a constant disadvantage is developed. The optimal deployment strategy is one that lets the proportion of the genetic entries be linearly dependent on their genetic value. By use of rankits as entries for genetic values, optimal solutions for deployment were calculated for a range of values of available entries (from 10 to 5,000) and preset diversity-related disadvantage-factors (the preset values correspond to mixtures of between 2 and 100 entries in identical proportions). The values are tabulated so they can be used by breeders. The superiority of the proposed strategy increases with the proportion of the available entries which are selected. In the situation that around half would have been selected if truncation selection was applied, the improvement in genetic gain compared to classical truncation selection is up to 18%. Thus, considerable improvements in gain are possible without any sacrifice in diversity. Applications are discussed with particular reference to clonal forestry. PMID- 24232900 TI - Dominance and recessiveness at loci for virulence against potato and tomato in Phytophthora infestans. AB - In this study we investigated the genetic control of virulence in the diploid fungal pathogen, Phytophthora infestans, against host resistance genes R1, R2, R3, and R4 (potato) and Ph1 (tomato). For four of these virulence traits, the presence or absence of segregation indicated conclusively which phenotype was dominant. We observed a 3?1 (virulent?avirulent) segregation on R2 in the progeny of parents which were both virulent, suggesting that virulence is dominant and both parents are heterozygous. In a cross in which one parent was virulent and the other avirulent on potato gene R3, all progeny tested were avirulent, so avirulence against R3 is dominant. The same virulent parent crossed with a different avirulent parent produced virulent and avirulent progeny in a 1?3 ratio, indicating that a second locus may be involved. The progeny of two parents virulent on R4 segregated for virulence and avirulence, so virulence against R4 is dominant. For Ph1, a 1?3 segregation in the progeny of two avirulent parents showed that the avirulent phenotype is dominant, and a 3?1 ration in a second cross suggested the involvement of a second locus. The segregations for virulence against R1 did not indicate which phenotype was dominant, but did suggest singlelocus control. PMID- 24232901 TI - Variability for restriction fragment lengths and phylogenies in lentil. AB - Thirty accessions of domesticated (Lens culinaris ssp. culinaris) and wild (L. culinaris ssp. orientalis, L. culinaris ssp. odemensis, L. nigricans ssp. ervoides and L. nigricans ssp. nigricans) lentil were evaluated for restriction fragment length polymorphisms (RFLPs) using ten relative low-copy-number probes selected from partial genomic and cDNA libraries of lentil. Nei's average gene diversity was used as a measure of genetic variability for restriction fragment lengths within subspecies and a dendrogram was constructed from genetic distance estimates between subspecies. The wild lentils L. culinaris ssp. orientalis and L. culinaris ssp. odemensis showed the greatest variability for restriction fragment lengths and were closely positioned to domesticated lentil in the dendrogram. Little variability for restriction fragment lengths was observed within accessions of L. nigricans ssp. ervoides and L. nigricans ssp. nigricans. This observation is consistent with a previously published proposal that nigricans may have been independently domesticated. Estimates of genetic variability based on RFLPs tended to be greater than estimates from isozymes. PMID- 24232902 TI - Genomic organization of the ribosomal DNA of sorghum and its close relatives. AB - The structure and organization of the ribosomal DNA (rDNA) of sorghum (Sorghum bicolor) and several closely related grasses were determined by gel blot hybridization to cloned maize rDNA. Monocots of the genus Sorghum (sorghum, shattercane, Sudangrass, and Johnsongrass) and the genus Saccharum (sugarcane species) were observed to organize their rDNA as direct tandem repeats of several thousand rDNA monomer units. For the eight restriction enzymes and 14 cleavage sites examined, no variations were seen within all of the S. bicolor races and other Sorghum species investigated. Sorghum, maize, and sugarcane were observed to have very similar rDNA monomer sizes and restriction maps, befitting their close common ancestry. The restriction site variability seen between these three genera demonstrated that sorghum and sugarcane are more closely related to each other than either is to maize. Variation in rDNA monomer lengths were observed frequently within the Sorghum genus. These size variations were localized to the intergenic spacer region of the rDNA monomer. Unlike many maize inbreds, all inbred Sorghum diploids were found to contain only one rDNA monomer size in an individual plant. These results are discussed in light of the comparative timing, rates, and modes of evolutionary events in Sorghum and other grasses. Spacer size variation was found to provide a highly sensitive assay for the genetic contribution of different S. bicolor races and other Sorghum species to a Sorghum population. PMID- 24232903 TI - Phylogenetic relationships of Triticum tauschii, the D genome donor to hexaploid wheat : 3. Variation in, and the genetics of, seed esterases (Est-5). AB - Isoelectric focusing of seed esterase (Est-5) isozymes in 79 T. tauschii accessions from diverse sources revealed the presence of six different seed esterase phenotypes. In one of these phenotypes, exclusive to a var. meyeri accession (AUS 18989), no detectable enzymatic activity was observed. Segregation in crosses between T. tauschii (D(t)) accessions confirmed three of the seed esterase phenotypes to be alleles of the designated Est-D (t)5 gene locus; the inheritance pattern of these isozymes was not affected by the subspecies differences between the parents. On the bases of variation in Est-5 and their Glu 1 and Gli-1 gene loci (in a previous study in this series), only three strangulata accessions showed consistent homology with their prevalent gene expression in the D genome of hexaploid wheat. The implications of these observations for further interpreting the phyletic nature of the D genome donor in natural hexaploid wheat synthesis are also reported. PMID- 24232904 TI - Relationships between some genetic parameters and test environments in open pollinated families of Pinus elliottii in South Africa. AB - Growth traits, stem form and branch characteristics in three series of well replicated trials, comprising open-pollinated families of Pinus elliottii Engelmann, were analysed to investigate whether the absolute value of the component of variance for family effect and its relative value (which is equivalent to one-quarter of heritability on individual values) were related, with trial averages of the traits studied taken as productivity indices of the sites tested. The first series, called the foreign selection series, consisted of four trials comprising open-pollinated families from single clones from a Florida seed orchard and from selected trees in Queensland, Australia. Two trials were established in the eastern Transvaal, at Tweefontein and Frankfort State Forests (SF), and two in Zululand, at Dukuduku and KwaMbonambi SF. The second series, called the Zululand selection series, consisted of open-pollinated families from single trees selected in Zululand that were compared in three trials: in the eastern Transvaal at Wilgeboom SF, in Zululand at Dukuduku SF and in the southern Cape at Lottering SF. The third series, called the South African selection series, consisted of open-pollinated families from single trees selected in the different forest areas of South Africa and compared in four trials: two trials in the eastern Transvaal at Tweefontein and Mariti SF and two in the Natal province at Dukuduku and Weza SF. Some positive and linear relationships between absolute sizes of the variance component for family and trial average for all traits studied, except stem form, were discernible for the foreign selections and for the Zululand selections. The South African selections presented a more erratic pattern of variation. However, when the origin of the genetic material was disregarded, the positive trends were undeniable. Curvilinear relationships between relative values and site averages were discernible, when the origin of the genetic material was disregarded. Further research is needed in order to confirm the suggested effect of site on genetic expressivity of open-pollinated families of slash pine grown in South Africa. PMID- 24232905 TI - Time of detection of recessive genes: effects of system of mating and number of examined individuals. AB - The elapsed time from the appearance of a single copy of a recessive gene in a population with separate sexes until the first detection of a recessive homozygote has been analyzed using simulation techniques. Several systems of mating frequently used in laboratory maintenance and artificial selection processes have been the subject of this study. The expected time of detection (T) in each system of mating is described by a function of number of parents (N) and the factor K that when multiplied by N gives the number of examined individuals per generation (e.g. T=1.6+1.8 (N/K) (1/3) for the mass-mating system). Although the expected time of detection changes greatly depending on the system of mating and on the K value (the causes are discussed), both the time scale (N (1/3)) and the coefficient of variation of the distribution of the times of detection (2/3) seem to be unaffected. The additional reduction of the effective population number caused by artificial selection on a heritable trait modifies the expected detection time in a minor way unless both high heritability and high selection intensity are involved. PMID- 24232906 TI - Influences of testing sites on the genetic correlations in open-pollinated family trials of Pinus elliottii in South Africa. AB - Two series of open-pollinated family trials of Pinus elliottii, the so-called foreign selection series and the Zululand selection series were repeated, respectively, on four and three sites situated in sub-tropical and cooler temperate climates of the summer rainfall and constant rainfall areas of South Africa. These series were studied in order to determine how testing sites influence the genetic correlations between traits commonly measured in progeny trials. No trend was detected between site index and genetic correlation, but site drastically changed the size and sign of the genetic correlations between growth traits and stem form. Even the genetic correlation between height and diameter at breast height was strongly affected by site. PMID- 24232907 TI - Analysis of phylogenetic relations of durum, carthlicum and common wheats by means of comparison of alleles of gliadin-coding loci. AB - Polymorphism and inheritance of wheat storage protein, gliadin, of durum (macaroni) and carthlicum wheats have been studied. Analysis of gliadin in 78 cultivars and in F2 seeds of intercultivar crosses of durum wheat revealed three different chromosome 1A-encoded blocks of components similar to those found in common wheat (GLD1A2, GLD1A18, GLD1A19). Most of the durum cultivars studied had these three blocks; GLD1A2 was also frequent in common wheat. In contrast, all chromosome 1B-encoded blocks of durum clearly differed in component composition from those found in common wheat. Therefore, durum could not be an ancestor or a derivate of recent bread wheat. Analysis of gliadin in the collection of carthlicum wheat (14 accessions) revealed several suspected chromosome 1A, 1B, and 6A-controlled blocks, some of which were similar to those in common wheat, while others were different. Therefore, carthlicum is likely to be an ancestor or a derivate of some forms of bread wheat. There were also chromosome 1A and 6A-, but not 1B-encoded blocks which were identical in durum and carthlicum wheats. The results confirm that all three wheats share the same genome A, but emphasize the heterogeneity of genotypes among donors of this genome. Discovery of identical blocks in tetraploids and hexaploids indicates polyphyletic [from different genotypes of donor (s)] origin of these wheats. PMID- 24232908 TI - Efficient production of doubled haploid plants through colchicine treatment of anther-derived maize callus. AB - A chromosome doubling technique, involving colchicine treatment of an embryogenic, haploid callus line of maize (Zea mays L., derived through anther culture), was evaluated. Two colchicine levels (0.025% and 0.05%) and three treatment durations (24, 48, and 72 h) were used and compared to untreated controls. Chromosome counts and seed recovery from regenerated plants were determined. No doubled haploid plants were regenerated from calli without colchicine treatment. After treatment with colchicine for 24 h, the callus tissue regenerated about 50% doubled haploid plants. All of the plants regenerated from the calli treated with colchicine for 72 h were doubled haploids, except for a few tetraploid plants. No significant difference in chromosome doubling was observed between the two colchicine levels. Most of the doubled haploid plants produced viable pollen and a total of 107 of 136 doubled haploid plants produced from 1 to 256 seeds. Less extensive studies with two other genotypes gave similar results. These results demonstrate that colchicine treatment of haploid callus tissue can be a very effective and relatively easy method of obtaining a high frequency of doubled haploid plants through anther culture. PMID- 24232909 TI - Relationship of cyst nematode gene frequencies to soybean resistance. AB - Soybean (S, Glycine max (L.) Merr.) lines with relatively few cysts of soybean cyst nematode (CN, Heterodera glycines Ichinohe) populations are usually called CN-resistant. The phenotype of number of cysts per plant is of the CN-S (Cyst Nematode-Soybean) association and determined by the interactions of genes for avirulence-resistance. The acronym "alins" was proposed for these alleles for incompatibility, with "xalin" representing the interaction X of one microsymbiont malin with its host h-alin. These alins are dominant in the gene-for-gene model but may be mostly recessive with CN-S. Definitive genetic studies have been hindered by the heterogeneity of sexually reproducing CN populations and lack of the appropriate genetic models. Loegering's abstract interorganismal genetic model was modified so that one model represented all four possible interactions of dominant-recessive alins for an incompatible phenotype. This involved redefining the Boolean algebra symbol 1 to represent both the alins AND their frequencies. The model was used to derive the relationship: {ie893-01} where the expectation E of cysts (of any CN-S combination, as proportion of number of cysts on a check cultivar) is proportional to the product Pi of CN genotypic frequencies expressed as functions of m-alin frequencies. Each m-alin is at a different locus, i.e., {ie893-02}. The number of terms multiplied for each CN-S is equal to the number of alins in the S line (or F2 plant). There are too many unknowns in the equation to solve for any of them. The relationship does explain the continuous distributions of phenotypes that were nearly always observed. Basic genetic principles were used to concurrently derive the models and to obtain discontinuous distributions of numbers of cyst phenotypes in segregating generations due to one recessive alin in a CN-"susceptible" soybean line. PMID- 24232910 TI - Recombination of R-D chromosome in pollen plants cultured from hybrid of 6x Triticale x common wheat. AB - Ninety-three pollen plants derived from the hybrid F1 of 6x Triticale x common wheat were observed cytologically. The rye chromosomes presented in these plants were identified by Giemsa-banding. Pollen plants having chromosome constitution 2n = 24 in haploids and 2n=46 in diploids were found to be predominant. The chromosome distributions of the R and D genome are different. R chromosomes distributed randomly and tended to full combination in offspring, but D chromosomes distributed non-randomly and tended to maintain intact. PMID- 24232912 TI - Do the blinds smell better? AB - If people lose a sense organ, there is thought to be an increase in the remaining sensory functions. Previous studies showed ambiguous results on this topic. In a prospective matched pair case-control study on 46 blind and 46 normal-sighted subjects, the olfactory performance was examined using the Sniffin' Sticks Test [threshold-discrimination-identification (TDI) test], determining the olfactory threshold, the identification and the discrimination performance. There was no significant difference between the groups. Neither the overall olfactory performance (TDI score) nor any of its subtests did correlate with the vision or with the duration of blindness. The study could not detect any superior smell abilities of blind subjects as compared to sighted subjects. PMID- 24232913 TI - Molecular epidemiology of Korean porcine sapeloviruses. AB - To evaluate the prevalence and genetic diversity of porcine sapeloviruses (PSVs) in Korea, a total of 100 diarrhea fecal samples from pigs were analyzed by RT-PCR and nested PCR assays with primer pairs specific for the VP1 gene. Overall, 34 % of the diarrhea samples tested positive for PSV, and a high proportion of infections occurred along with a variety of other enteric viruses and bacteria. Genomic and phylogenetic analysis of the VP1 genes revealed pronounced genetic diversities between PSVs from Korean and elsewhere. Our results indicate that PSV infections are very common in Korean pigs with diarrhea. The infecting strains are genetically diverse. PMID- 24232914 TI - Phylogenetic analysis of New Zealand tomato spotted wilt virus isolates suggests likely incursion history scenarios and mechanisms for population evolution. AB - Tomato spotted wilt virus (TSWV) is an internationally significant pathogen with a wide host range, vectored by thrips. We have studied the sequence variation and evolutionary mechanisms at play in parts of the L, M and S subgenomes of 23 New Zealand TSWV isolates collected between 1992 and 2009, aiming to identify the possible geographic origins of isolates. Maximum-likelihood-based phylogenetic analyses of New Zealand and overseas TSWV isolates placed the L and M subgenome sequences of two isolates (MAF04 and PFR04) in distinct clades composed primarily of Korean, Japanese and Chinese isolates, in contrast to the remaining 21 isolates, which clustered with a cosmopolitan group of isolates. The nucleocapsid (N) gene sequences of MAF04 and PFR04 plus MAF02 clustered with Japanese isolates. Consequently, we postulate that these isolates may represent a distinct incursion into New Zealand, but we do not have enough evidence to indicate an incursion pathway. Alternately, these isolates may have arrived with an incursion that included a mixture of TSWV isolates of diverse international origins. The sequences of four of the TSWV isolates contained a number of sites with a mixture of nucleotides, suggesting that these isolates either consisted of several sequence variants or were from plants with mixed infections. One isolate (MAF02) was shown to be a either a reassortant or an S subgenome recombinant. Large amounts of low-level polymorphism were detected with low amino acid change fixation rates (purifying selection). Negative selection was indicated at four amino acid sites in the New Zealand TSWV N gene sequences. PMID- 24232915 TI - Understanding internalization of rotavirus VP6 nanotubes by cells: towards a recombinant vaccine. AB - Rotavirus VP6 nanotubes are an attractive option for a recombinant vaccine against rotavirus disease. Protection against rotavirus infection and an adjuvant effect have been observed upon immunization with VP6 nanotubes. However, little information exists on how VP6 nanotubes interact with cells and trigger an immune response. In this work, the interaction between VP6 nanotubes and different cell lines was characterized. VP6 nanotubes were not cytotoxic to any of the animal or human cell lines tested. Uptake of nanotubes into cells was cell-line-dependent, as only THP1 and J774 macrophage cells internalized them. Moreover, the size and spatial arrangement of VP6 assembled into nanotubes allowed their uptake by macrophages, as double-layered rotavirus-like particles also displaying VP6 in their surface were not taken up. The internalization of VP6 nanotubes was inhibited by methyl-beta-cyclodextrin, but not by genistein, indicating that nanotube entry is specific, depends on the presence of cholesterol in the plasma membrane, and does not require the activity of tyrosine kinases. The information generated here expands our understanding of the interaction of protein nanotubes with cells, which is useful for the application of VP6 nanotubes as a vaccine. PMID- 24232911 TI - Endovascular laser-tissue interactions and biological responses in relation to endovenous laser therapy. AB - Endovenous laser treatment (ELT) has evolved into a frequently employed modality for the treatment of leg varicose veins. Due to the very high complete response rates, minimal complications and side effects, and the possibility to monitor therapeutic outcome noninvasively by duplex ultrasound, a considerable amount of reports have been published on clinical and translational studies, whereas disproportionally few studies have been performed to elucidate the molecular and cellular basis for post-ELT vessel obliteration. Consequently, this review addresses the putative molecular and cellular mechanisms responsible for varicose vein obliteration following laser irradiation in the context of endovenous laser tissue interactions. First, the histological profile of laser-treated varicose veins is summarized, and an account is given of the temporal and spatial dynamics of cells involved in inflammation and remodeling in the heat-affected vein segment. Inasmuch as thrombotic occlusion of the venous lumen blocks circulatory access to the affected vessel segment and thermal damage in the vascular wall causes most cells to die, the majority of cells involved in inflammation and remodeling have to be recruited. Second, the (possible) biochemical triggers for the chemotactic attraction of immune cells and fibroblasts are identified, comprising (1) thermal coagula, (2) thrombi, (3) dead and dying cells in the vein wall, and (4) thermally denatured extracellular matrix proteins in the vein wall. The molecular biology underlying the chemotactic signaling and subsequent obliterative remodeling is elucidated. Finally, the relative contribution of every biochemical trigger to obliterative remodeling is addressed. PMID- 24232916 TI - Complete genome sequence of invertebrate iridovirus IIV-25 isolated from a blackfly larva. AB - Members of the family Iridoviridae are animal viruses that infect only invertebrates and poikilothermic vertebrates. Invertebrate iridovirus 25 (IIV-25) was originally isolated from the larva of a blackfly (Simulium spp., order Diptera) found in the Ystwyth river near Aberystwyth, Wales. IIV-25 virions are icosahedral, have a diameter of ~130 nm, and contain a dsDNA genome of 204.8 kbp, with a G+C content of 30.32 %, that codes for 177 proteins. Here, we describe the complete genome sequence of this virus and its annotation. This is the fifth genome sequence of an invertebrate iridovirus reported. PMID- 24232917 TI - Weight misperception, self-reported physical fitness, dieting and some psychological variables as risk factors for eating disorders. AB - The aims of the current study were to explore possible gender differences in weight misperception, self-reported physical fitness, and dieting, and to analyze the relationship between these variables and others, such as self-esteem, body appreciation, general mental health, and eating- and body image-related variables among adolescents. In addition, the specific risk for eating disorders was examined, as well as the possible clusters with respect to the risk status. The sample comprised 655 students, 313 females and 342 males, aged 16.22 +/- 4.58. Different scales of perceived overweight, self-reported physical fitness and dieting together with the Body Mass Index (BMI) were considered along with instruments such as the International Physical Activity Questionnaire (IPAQ), General Health Questionnaire (GHQ-28), Self-Esteem Scale (SES), Body Appreciation Scale (BAS) and Eating Disorders Inventory-2 (EDI-2). Since some gender differences were found with respect to these adolescent groups, it is necessary to design prevention programs that not only focus on traditional factors such as BMI or body image, but also on elements like weight perception, self-reported fitness and nutritional education. PMID- 24232918 TI - Diastereoselective alpha-C-H functionalization of aliphatic N-heterocycles: an efficient route to ring fused oxazines. AB - A novel method for direct C-H functionalization of saturated N-heterocycles allowing easy access to synthetically as well as biologically important and structurally diverse ring-fused oxazines is developed. The method is operationally simple and highly diastereoselective. Moreover, it is efficient in functionalizing broad classes of both cyclic and acyclic amines including the substrates that are otherwise difficult to functionalize. PMID- 24232920 TI - Reversible variations in the methylation pattern of carrot DNA during somatic embryogenesis. AB - Twenty five clones from a carrot genomic library were used as probes to detect variations in the 5-methyl-cytosine pattern during somatic embryogenesis. The majority of them evidenced an invariant pattern. With two clones however, differences were found between the adulttype DNA pattern and the embryonic one. The level of transcription of the relevant DNA fragments during embryogenesis was investigated by Northern blotting. One of the two probes did not show signals in any of the developmental stages whereas the other showed developmentally regulated expression. This fact suggests a novel strategy for cloning developmentally expressed functions. PMID- 24232919 TI - Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice. AB - Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD). We generated a tet-repressible muscle-specific Pitx1 transgenic mouse model which develops phenotypes of muscular dystrophy after the PITX1 expression is induced. In this study, we attempted to block the translation of PITX1 protein using morpholinos. Three groups of the transgenic mice received intravenous injections of phosphorodiamidate morpholino oligomers (PMO) (100 mg/kg), octaguanidinium dendrimer-conjugated morpholino (vivo-morpholino) (10 mg/kg), or phosphate buffered saline (PBS) after the PITX1 expression was induced. Immunoblotting data showed that PITX1 expression in the triceps and quadriceps was significantly reduced 70% and 63% by the vivo-morpholino treatment, respectively. Muscle pathology of the mice treated with the vivo-morpholino was improved by showing 44% fewer angular-shaped atrophic myofibers. Muscle function determined by grip strength was significantly improved by the vivo-morpholino treatment. The study showed that systemic delivery of the vivo-morpholino reduced the PITX1 expression and improved the muscle phenotypes. Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. The findings of this study suggest that the same principle may be applied to suppress the aberrantly expressed DUX4 in FSHD. PMID- 24232921 TI - Direct gene transfer to plant protoplasts by electroporation by alternating, rectangular and exponentially decaying pulses. AB - The efficiency of electroporation of sugar beet (Beta vulgaris L.) and tobacco (Nicotiana tabacum L.) protoplasts by alternating, rectangular and exponentially decaying pulses was studied by assaying transient expression of an introduced gene for chloramphenicol acetyltransferase. A simple device for electroporation by alternating current was constructed. The mains (220 V) were used as power supply and the pulse duration was controlled by the blow-out of a small fuse. Electroporation of sugar beet protoplasts by alternating current and exponentially decaying pulses resulted in 3-4 fold higher transient expression compared to rectangular pulses. Transient expression in tobacco protoplasts electroporated by exponentially decaying pulses was 30 % and 85 % higher than when electroporated by rectangular and alternating current pulses, respectively. PMID- 24232922 TI - Somatic embryogenesis and plant regeneration from protoplasts of asparagus (Asparagus officinalis L.). AB - Protoplasts were isolated from embryogenic calli of Asparagus officinalis L. cv. Mary Washington and cultured in 1/2 MS medium with 1 mg/l NAA, 0.5 mg/l zeatin, 1 g/l L-glutamine, 0.6 M glucose and 0.1% Gellan Gum. Protoplasts started to divide after 3-4 d of culture and formed visible colonies after 30 d of culture. The percentage of colony formation (plating efficiency) was 7.2%. The colonies were then transferred onto Gellan Gum-solidified MS medium containing 1 mg/l 2,4-D and 3% sucrose for further growth. Somatic embryos were induced from all colonies of 0.5-1.0 mm size after transferring to 1/2 MS medium lacking growth regulators. After treating these somatic embryos (1-3 mm) in distilled water for a week, 30 40% of them germinated normally and grew into plantlets 20-30 d after transplanting on 1/2 MS medium containing 1 mg/l IBA, 1 mg/l GA3 and 1% sucrose. These protoplast-derived plants were diploid with 20 chromosomes. PMID- 24232923 TI - Depigmentation and inhibition of cell growth of B-16 melanoma cells by compounds isolated from Paeonia suffruticosa callus. AB - The anther segments of Paeonia suffruticosa Andrews were cultured for callus formation on MS medium supplemented with 2,4-D and BAP(each 1 mg/l) in the dark at 25 degrees C for six weeks. Gallic acid, methyl gallate, ethyl gallate and 1,2,3,4,6-penta-O-galloyl-beta-D-glucose were isolated from the ethanol extract of callus, and paeoniflorin was identified. A dose of 5 MUg/ml pentagalloyl glucose resulted in depigmentation of B-16 melanoma cells without inhibition of cell propagation. PMID- 24232924 TI - Characterization and regeneration of wheat (Triticum aestivum L.) embryogenic cell suspension cultures. AB - Stable cell suspension cultures were established from two types of calli (one compact, nodular and embryogenic, the other friable and embryogenic) derived from cultured immature embryos of wheat (cv FLA302). Only aged calli, which had been subcultured for at least 5-8 months, formed suspensions comprised mainly of groups of small, round, densely cytoplasmic, starch-containing cells. Only the embryogenic suspension derived from the aged, compact and nodular callus formed distinct somatic embryos when plated on regeneration media containing IAA and zeatin. Upon subsequent transfer to fresh regeneration medium more than 200 green rooted plants were obtained. PMID- 24232925 TI - Stable transfer and expression of chimeric genes in licorice (Glycyrrhiza uralensis) using an Ri plasmid binary vector. AB - The pharmaceutically important plant, licorice (Glycyrrhiza uralenesis Fisher), was transformed with a binary vector system of an Ri plasmid, pRi15834, and a mini Ti vector, pGSGluc1, containing chimeric neo and gus genes. The transgenic state of transformed roots was confirmed by detection of agropine and mannopine and by Southern blot hybridization with T-DNA of pGSGluc1. One to three copies of T-DNA of pGSGluc1 was integrated into the genomic DNA of G. uralensis. The expression of chimeric neo and gus genes driven by TR 1' and 2' promoters, respectively, was demonstrated by enzymatic assays. Histochemical analysis showed that the chimeric TR2'-gus gene was expressed specifically in phloem and pericycle tissues of the transformed licorice roots. PMID- 24232926 TI - Plant regeneration from mesophyll protoplasts of Diplotaxis muralis, a wild crucifer. AB - Mesophyll protoplasts from leaves of aseptically grown shoot tips of Diplotaxis muralis were isolated (6.2-7.1*10(5) protoplasts/g fresh weight of tissue) using one step enzyme digestion. The protoplasts (71% viability) underwent divisions (4.2+0.1%) on plating in M8PS2 medium and ultimately formed calli with 0.45+0.03% plating efficiency. Plant regeneration could be achieved both through embryogenesis and organogenesis. The efficiency of plant regeneration through organogenesis was 9 times higher than embryogenesis. Forty eight out of 52 plants regenerated so far from 3 independent experiments were normal with respect to fertility and meiotic chromosomal behavior. PMID- 24232927 TI - Plant regeneration by organogenesis in Vitis rootstock species. AB - A procedure for the regeneration of Vitis rootstocks plantlets by organogenesis from foliar tissues is described. Leaves from mature plants grown in growth chambers or from plantlets grown in tubes were wounded with a scalpel and cultured on a modified Murashige and Skoog liquid medium containing different concentrations of benzyl-aminopurine. The presence of benzyl-aminopurine is required for shoot formation. The age of the source explant, the composition of the culture medium and the culture temperature are important parameters of the regeneration process. PMID- 24232928 TI - Detection of bacterial chitinase activity in transformed plant tumour cells using a specific exochitinase substrate. AB - Methods for the detection of bacterial chitinase activity were compared. The soluble substrate p-nitrophenyl-beta-D-N,N diacetyl chitobiose (NDC) was more sensitive in detecting purified chitinase of Serratia marcescens than assays measuring degradation of a solid chitin substrate by either radiochemical or colorimetric means. A chimaeric gene containing a S. marcescens chitinase gene under control of a Cauliflower Mosaic Virus 35S promoter and nopaline synthase terminator sequences was constructed and transferred to tobacco tumour cells using Agrobacterium tumefaciens as a vector. The rate of hydrolysis of the NDC substrate was three fold greater with cell extracts of both pooled and individual tumours carrying the chimaeric chitinase gene than in control tumours. It was calculated from the enzyme activity data that the foreign bacterial chitinase contributed 0.1% of the total soluble protein in transformed plant cells. This level of expression of this gene was not detectable using the less sensitive assays employing solid chitin substrate. These results indicate that NDC is a preferable substrate for assaying bacterial chitinase in transformed plant cells. PMID- 24232929 TI - Efficient, direct plant regeneration from stem segments of chrysanthemum (Chrysanthemum morifolium Ramat. cv. Royal Purple). AB - Direct plant regeneration was obtained from fresh chrysanthemum (Chrysanthemum morifolium Ramat. cv. Royal Purple) stem segments cultured on Murashige and Skoog's (1962) basal media supplemented with 6-benzylaminopurine (BAP, 0.5-2.0 mg/l) and alpha-naphthaleneacetic acid (NAA, 0.2-2.0 mg/l). The morphogenetic potential varied with the developmental stage of the stem explant. The highest percentage of shoot formation (100%) and greatest average number of shoots per explant (14.6) were observed on stem segments taken from the top of the cutting. This organogenetic capacity decreases in the more mature stem. Normal, flowering plants were obtained three to four months after culture. PMID- 24232930 TI - In vitro propagation through axillary bud multiplication in different mulberry genotypes. AB - Axillary buds from 5 genotypes of mulberry belonging to 4 species were cultured on modified MS basal medium. A total of 30 media combinations were tried for all the genotypes. The response of axillary buds and the requirement for growth regulators varied with genotype. In Morus indica BAP (0.25-0.5 mg/l), and in M. alba and M. rotondifolia GA3 (0.5-1.0 mg/l)were found to induce sprouting. Two genotypes of M. bombycis, namely Schimanochi and Mizusawa, developed healthy shoots on the incorporation of 2,4-D (0.5-1.0 mg/l) and BAP (0.5-2.0 mg/l), respectively. IBA (0.5 mg/l), along with cytokinin/auxin/gibberellin, had no effect on bud growth but helped root induction. Shoots developed from the axillary buds were further multiplied as nodal explants. MS basal medium supplemented with 0.5 mg/l IBA and LS vitamins was found best to produce healthy plantlets in all the genotypes. An average 89% survival was observed on transferring the plantlets to soil. PMID- 24232931 TI - Hyphal growth of Phytophtora cinnamomi on pine callus tissue. AB - A procedure was developed which demonstrates the expression of differential resistance in pine callus tissues to the fungal pathogen Phytophthora cinnamomi Rands. Callus tissues were maintained on a modified Murashige and Skoog medium with 10(-5)M 2,4-D and inoculated with hyphae of P. cinnamomi at 26 degrees C in the dark. The number of intracellular hyphae was used as an index of resistance. Loblolly and loblolly * shortleaf pine hybrids were determined to be more resistant to infection and invasion by the fungus than were shortleaf and Virginia pine. PMID- 24232932 TI - Micropropagation of an endangered plant species: Coronopus navasii (Brassicaceae). AB - Plantlets of Coronopus navasii, an endangered species from SE Spain, were successfully regenerated from shoot and root segments excised from young seedlings. Initiation of multiple buds and development of leaves were obtained in MS modified medium plus l mg/l BAP and 0.1 mg/l NAA. Rooting was achieved by transfer of the isolated shoots to fresh MS medium without plant growth regulators. Plant survival of 47% was obtained six weeks after removal from in vitro culture conditions. PMID- 24232933 TI - Associations between age-related macular degeneration, Alzheimer disease, and dementia: record linkage study of hospital admissions. AB - IMPORTANCE: The potential association between age-related macular degeneration (AMD) and Alzheimer disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral, and treatments. OBJECTIVES: To determine whether individuals admitted to the hospital with AMD were significantly more or less likely to develop AD or dementia in the following years, as well as to assess whether people with AD or dementia were significantly more or less likely to be admitted to the hospital for AMD treatment in the years following diagnosis of dementia. DESIGN, SETTING, AND PARTICIPANTS: An AMD cohort of 65,894 people was constructed from English National Health Service, linked hospital episode statistics from January 1, 1999, through February 28, 2011, by identifying computerized record abstracts for all people with an admission or day case care for AMD. A dementia cohort (168,092 people) and a reference cohort (>7.7 million people) were constructed in similar ways. MAIN OUTCOMES AND MEASURES: Risk of AD or dementia following AMD and risk of AMD following AD or dementia. Rate ratios were calculated based on standardized rates of AD and dementia in the AMD cohort, as well as standardized rates of AMD in the AD and dementia cohort, relative to those in the reference cohort. RESULTS The risk of AD or dementia following AMD was not elevated. The rate ratio was 0.86 (95% CI, 0.67-1.08) for AD and 0.91 (0.79-1.04) for dementia. The likelihood of being admitted for AMD following AD or dementia was very low: the rate ratio was 0.04 (0.01-0.10) for people with AD and 0.07 (0.04-0.11) for those with dementia. CONCLUSIONS AND RELEVANCE: These neurodegenerative conditions may share environmental risk factors and histopathologic features. However, considering AD and other dementia after AMD, their coexistence at the individual level is no different from that expected by chance. Our data also suggest that patients in England with dementia may be substantially less likely to receive AMD treatment. Further research is required to determine whether people with dementia receive appropriate investigation and treatment for AMD, as well as identify and address potential barriers. PMID- 24232935 TI - [Cardiovascular effects of hormonal contraception.] PMID- 24232934 TI - Intraoperative dynamic assessment of the posterior communicating artery and its branches by indocyanine green videoangiography. AB - BACKGROUND: True hemodynamic assessment of the posterior communicating artery (PComA) by preoperative angiography in terms of its perforators and configuration (adult vs. fetal vs. transitional) can be challenging in the surgical treatment of aneurysms involving the PComA, posterior cerebral artery, and basilar artery. Indocyanine green videoangiography (ICG-VA) is a widely accepted new technique in the surgical treatment of intracranial aneurysms to assess the patency of the parent artery, branches, and residual flow within the aneurysm after clipping. CASE DESCRIPTION: Here we report two cases in which ICG-VA was utilized to assess either the direction of flow in the PComA or preservation of the PComA perforators with temporary clip application before dividing the PComA. CONCLUSIONS: Our experience is that ICG-VA can be used to assess the main trunk, and perforating branches of the PComA providing real-time, dynamic intraoperative information of the surgical field. Therefore we suggest that ICG-VA may increase the safety of surgical treatment of aneurysm involving PComA. PMID- 24232936 TI - Gamma-glutamyl transpeptidase from two plant growth promoting rhizosphere fluorescent pseudomonads. AB - Glutathione is the most abundant non-protein thiol compound present in many cells. Because this molecule is involved in many physiological processes, each cell maintains a critical level of glutathione. Gamma-glutamyl transpeptidase (GGT, E.C.2.3.2.2) is the key enzyme involved in the glutathione cycle. In the present study, GGT was isolated from two plant growth promoting rhizosphere isolates, Pseudomonas protegens strain Pf-5 and Pseudomonas fluorescens strain PfT-1. GGT in these strains is located in the periplasm and possessed good hydrolytic activity at pH 8.0. Strains Pf-5 and PfT-1 showed maximum enzyme activity when grown at 30-35 degrees C. The ggt gene from both the strains was cloned in pGEM-T cloning vector and sequenced. Subsequently, GGT expressed in Escherichia coli BL21(DE3) using the pET-28a(+) expression vector was purified and characterized. The enzymes are active in a wide range of pH and some divalent cations significantly enhanced the hydrolytic activity. These enzymes showed higher thermal stability as compared to those of other mesophilic strains, as they retained ~50 % of activity at 50 degrees C even after 12 h of incubation. The enzymes could also tolerate up to 3.0 M NaCl. PMID- 24232937 TI - [Biometry in the growth of the high myopic eye in childhood]. AB - PURPOSE: To determine if the growth of the axial length measured by optical and ultrasound biometry in a pediatric population of high myopes is significant, as well as significant variation of lens thickness, anterior chamber depth, corneal curvature and ophthalmoscopic findings during follow-up. METHODS: A pediatric population (mean age: 8.7 years old) of 11 high myopic eyes (mean initial refractive error: -11.28 D) was submitted to serial evaluation over a 9-months period including optical (IOLMaster, Zeiss) and ultrasound biometry (Ultrascan, Alcon, contact technique), cycloplegic refraction, indirect ophthalmoscopy and fundus photography. RESULTS: During a 9-months period, eye growth was significant in 64% (7 eyes) and did not occur in 36% (3 eyes), with change in the mean axial length (pre=26.76 mm; final=26.98 mm). During this period, refractive spherical equivalent increased in 45% (5 eyes), did not show variation in 27% (3 eyes), with a change in mean refraction (pre=-11.28 D; final=-11.69 D). There was no statistically significant variation of lens thickness, anterior chamber depth, corneal curvature and ophthalmoscopic findings. CONCLUSION: Ocular globe growth (axial length) measured by optic and ultrasound biometry was significant in the high myopic pediatric population examined. The findings suggest that axial length variation preceded variation of other structures in the sample examined. In a group of children with high myopia followed during a 9-months period, ocular growth was demonstrated with variation of axial length either with optical or ultrasound biometry techniques, and change in mean refraction. Other parameters studied as lens thickness, anterior chamber depth and corneal curvature did not demonstrate variation during the time of the study. PMID- 24232938 TI - Longitudinal measurements of luminance and chromatic contrast sensitivity: comparison between wavefront-guided LASIK and contralateral PRK for myopia. AB - PURPOSE: The present study aimed to compare the postoperative contrast sensitivity functions between wavefront-guided LASIK eyes and their contralateral wavefront-guided PRK eyes. METHODS: The participants were 11 healthy subjects (mean age=32.4 +/- 6.2 years) who had myopic astigmatism. The spatial contrast sensitivity functions were measured before and three times after the surgery. Psycho and a Cambridge graphic board (VSG 2/4) were used to measure luminance, red-green, and blue-yellow spatial contrast sensitivity functions (from 0.85 to 13.1 cycles/degree). Longitudinal analysis and comparison between surgeries were performed. RESULTS: There was no significant contrast sensitivity change during the one-year follow-up measurements neither for LASIK nor for PRK eyes. The comparison between procedures showed no differences at 12 months postoperative. CONCLUSIONS: The present data showed similar contrast sensitivities during one year follow-up of wave-front guided refractive surgeries. Moreover, one year postoperative data showed no differences in the effects of either wavefront guided LASIK or wavefront-guided PRK on the luminance and chromatic spatial contrast sensitivity functions. PMID- 24232939 TI - Correlation between cup-to-disc ratio and cup/retrobulbar optic nerve diameter proportion assessed by high-resolution ultrasound in glaucomatous eyes. AB - PURPOSE: To investigate the correlation between the measurements of the cup/retrobulbar optic nerve diameter (C/OND) proportion obtained by high resolution 20-MHz B-mode ultrasound (US) and those of the cup/disc ratio (C/D) obtained by fundus biomicroscopy (BIO) and optical coherence tomography (OCT). METHODS: Thirty eyes of 15 glaucomatous patients with any C/D proportion were studied. All patients underwent examination of the vertical C/D by BIO with a 78D lens and time-domain OCT analysis, as well as the vertical C/OND proportion using 20-MHz US measurements. All data were analyzed by correlation and agreement tests. RESULTS: The Spearman test showed a strong correlation between C/D results obtained by BIO and the measurements of C/OND (US) (r=0.788, p<0.0001), and with C/D obtained by OCT (r=0.8529, p<0.0001). However, comparison of C/D results obtained with OCT to those obtained by with C/OND (US) showed only a moderate correlation (r=0.6727, p<0.0001). Bland-Altman analysis did not show good agreement between C/D (BIO) and C/OND (US). CONCLUSIONS: The results demonstrate that B-mode ultrasound examination with a 20 MHz probe can be a good additional method for the evaluation of the C/D ratio in glaucomatous patients, and may be considered as an alternative gross tool in glaucomatous patients with optic media opacities. PMID- 24232940 TI - Impact of chamber pressure and material properties on the deformation response of corneal models measured by dynamic ultra-high-speed Scheimpflug imaging. AB - PURPOSE: To study the deformation response of three distinct contact lenses with known structures, which served as corneal models, under different chamber pressures using ultra-high-speed (UHS) Scheimpflug imaging. METHODS: Three hydrophilic contact lenses were mounted on a sealed water chamber with precisely adjustable pressure: TAN-G5X (41% hydroxyethylmethacrylate/glycolmethacrylate, 550 um thick), TAN-40 (62% hydroxyethylmethacrylate, 525 um thick) and TAN-58 (42% methylmethacrylate, 258 um thick). Each model was tested five times under different pressures (5, 15, 25, 35 and 45 mmHg), using ultra-high-speed Scheimpflug imaging during non-contact tonometry. 140 Scheimpflug images were taken with the UHS camera in each measurement. The deformation amplitude during non-contact tonometry was determined as the highest displacement of the apex at the highest concavity (HC) moment. RESULTS: At each pressure level, the deformation amplitude was statistically different for each lens tested (p<0.001, ANOVA). Each lens had different deformation amplitudes under different pressure levels (p<0.001; Bonferroni post-hoc test). The thicker lens with less polymer (TAN-G5X) had a higher deformation (less stiff behavior) than the one that was thinner but with more polymer (TAN-40), when measured at the same internal pressure. The thinnest lens with less polymers (TAN-58) had a lower deformation amplitude (stiffer behavior) at higher pressures than the thicker ones with more polymer (TAN-40 and TAN-G5X) at lower pressures. CONCLUSIONS: UHS Scheimpflug imaging allowed for biomechanical assessment through deformation characterization of corneal models. Biomechanical behavior was more influenced by material composition than by thickness. Chamber pressure had a significant impact on deformation response of each lens. PMID- 24232941 TI - [Signs and symptoms of ocular surface disease in patients on topical intraocular pressure-lowering therapy]. AB - PURPOSE: To determine the prevalence of signs and symptoms of ocular surface disease (OSD) in patients using topical intraocular pressure-lowering therapy. METHODS: In this cross-sectional study, 40 patients were consecutively recruited from the glaucoma clinic of a public hospital located in Rio de Janeiro, Brazil. Eligible patients were 18 years of age or older, with primary open-angle glaucoma or ocular hypertension and on the same topical ocular therapy for at least 6 months. The following data were considered: sex, age, medication history and number of years on topical intraocular pressure-lowering therapy. All patients underwent an evaluation of the ocular surface which included: an interview using the Ocular Surface Disease Index(r) (OSDI(r)) questionnaire, break-up time, biomicroscopy, fluorescein corneal staining and rose Bengal ocular surface staining. RESULTS: The mean OSDI(r) score was 24.6 +/- 20.7. Most patients (67.5%) had an abnormal score on the OSDI(r) questionnaire. In 25% of patients, the score was consistent with mild symptoms, 12.5% with moderate symptoms and 30% with severe symptoms. Blepharitis and punctate keratitis were diagnosed in 42.5% and 20% of patients respectively. Tear film instability was observed in 75% of patients and ocular surface staining with rose Bengal in 35%. A positive statistically significant correlation (r=0.4; p=0.01) was found between OSDI(r) scores and the duration of topical intraocular pressure-lowering therapy. CONCLUSION: Patients with primary open-angle glaucoma or ocular hypertension on topical intraocular pressure-lowering therapy have high prevalence of OSD. Longer duration since diagnosis is significantly correlated with worsening of OSD symptoms. PMID- 24232942 TI - [Complications after Descemet's stripping endothelial keratoplasty]. AB - PURPOSE: To describe the complication rate and type of intraoperative and postoperative complications of Descemet stripping endothelial keratoplasty (DSEK). METHODS: Retrospective medical records review of patients who underwent DSEK between 2008 and 2010 at the Sorocaba Ophthalmological Hospital. The study was descriptive, using a quantitative approach. RESULTS: One hundred nineteen eyes of 118 patients were evaluated. According to the diagnoses, most patients were diagnosed with Fuchs' dystrophy (60 eyes, 50.4%), followed by patients with pseudophakic bullous keratopathy in 55 eyes (46.2%). The most common procedure performed was DSEK alone, performed in 65 eyes (54.6%), followed by the DSEK associated to phacoemulsification (PHACO-DSEK) in 47 eyes (39.5%) and DSEK associated to other surgeries (7 eyes, 5.9%). Eight patients were excluded from the study due to insufficient information in the surgical record. In relation to the intra-operative complications, isolated cases of pupillary block, irregular manual dissection of button, inverted implantation of the button, button-holing and posterior capsule rupture were noticed. Among the documented early postoperative complications, button detachment was observed in 21.5% of the DSEK alone group; 34.0% in PHACO-DSEK group and 57.1% when DSEK was held jointly with other surgical techniques. Regarding to late complications, interface haze was observed in 16.9%, 8.5% and 14.2%, and glaucoma was observed in 4.6%, 2.1% and 14.2% in DSEK, PHACO-DSEK and DSEK associated to other techniques, respectively. Post rejection graft failure was observed in 15.3% and 12.7% of the eyes after DSEK and. PHACO-DSEK, respectively. CONCLUSION: Endothelial corneal transplant accomplished in this sample showed a high rate of complications when compared to the conventional penetrating keratoplasty. The most frequent complications were related to detachment of the button and graft failure. PMID- 24232943 TI - [Corneal reepithelialization time with instillation of eye drops containing sodium hyaluronate and carboxymethylcellulose]. AB - PURPOSE: Evaluate the time of post-abrasion corneal re-epithelialization using commercially available eye drops, one of which containing 0.4% sodium hialuronate, and the other containing 1% carboxymethylcellulose, and compare them to the re-epithelialization without the drops. METHODS: 24 rabbits were used, which had the mechanical abrasion of the central 8 mm of their corneas done. These animals were divided in 3 groups. The first one received the drops containing 0.4% of sodium hialuronate, the second one received the drops containing 1% of carboxymethylcellulose and the third group did not receive any drugs. The evaluations took place every 24 hours through the analysis of digital pictures under cobalt blue light and coloring of the corneas with 2% fluorescein. The pictures were analyzed with the software Autocad 2009(r). The data was analyzed through the comparison of the total re-epithelialization time among the three groups RESULTS: The time of total re-epithelialization of the group using sodium hialuronate was on average 90 hours and the group using carboxymethylcellulose 105 hours, while the group using no drugs was 108 hours. There was a better performance of those groups using the drops and this difference can be proved statistically. CONCLUSION: The drops containing 0.4% of sodium hialuronate showed a higher efficiency rate compared to the drops containing 1% of carboxymethylcellulose, which was higher than the control group. The results of the present study show that the use of lubricants in the process of re-epithelialization are extremely valid and must be used frequently in ophthalmologic clinic. PMID- 24232944 TI - Assessment of pupillary influence in LASIK patients using a digital pupillometer and VQF 25 questionnaire. AB - PURPOSE: Identify ideal profiles in patients undergoing to photorefractive laser surgery with the aid of an automated pupillometry and psychometric analysis of patients with visual function questionnaire (VQF 25). METHODS: Seventy-seven patients undergoing photorefractive laser surgery laser (LASIK) were analyzed with the aid of an automated digital pupillometer based on an infrared camera coupled to the optical head of a videokeratography system. Patients underwent complete ophthalmic evaluation and documentation of the pupillary behavior under different intensities of illumination, simulating situations of everyday life. Visual quality function questionnaire, translated to Portuguese was assessed. RESULTS: All patients, regardless of pupillary change under varying conditions of illumination (scotopic, mesopic and photopic) showed improvement in all sub groups of the VQF 25. Pupil diameter was not the primary determinant of patients' visual satisfaction. CONCLUSION: Despite digital pupillometer has proven to be a useful tool in documenting and understanding of pupil behavior, a set of factors such as psycho-social profile, preoperative ametropy and final residual ametropy, contributed decisively to determine the degree of satisfaction of patients undergoing LASIK. PMID- 24232945 TI - [Complications in endothelial keratoplasty performed by cornea fellows]. AB - PURPOSE: To report early complications in endothelial keratoplasty performed by cornea fellows. METHODS: Retrospective study of endothelial keratoplasty performed by second-year cornea fellows. Described the early complications and its treatments. RESULTS: Thirty four endothelial keratoplasty were performed by cornea fellows, from July 2007 to August 2008. From this, 29 were Descemet stripping endothelial keratoplasty and 5 Descemet stripping automated endothelial keratoplasty; 14 combined with phacoemulsification and 1 with extracapsular cataract surgery. The main indication was Fuchs' dystrophy (18 cases), followed by bullous keratopathy (11 cases), primary failure after endothelial keratoplasty (4 cases) and congenital hereditary endothelial dystrophy (1 case). Main surgery complication was donor button detachment in 8 eyes (23.5%), followed by primary graft failure in 7 eyes (20.6%) and acute glaucoma after pupillary block in 1 eye (2.9%). CONCLUSIONS: The complication rate in this series, which were the first ever in a group of six cornea fellows, was high. This shows the steep learning curve for this surgical procedure. The assistance of an experienced surgeon could help to achieve a less steep learning curve with a lower complication rate. PMID- 24232946 TI - Impression cytology and in vivo confocal microscopy in corneas with total limbal stem cell deficiency. AB - PURPOSES: To describe corneal changes seen on in vivo confocal microscopy in patients with total limbal stem cell deficiency and to correlate them with cytological findings. METHODS: A prospective case series including 13 eyes (8 patients) with total limbal deficiency was carried out. Stem cell deficiency was diagnosed clinically and by corneal impression cytology. Confocal images of the central cornea were taken with the Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany). RESULTS: Impression cytology of the cornea revealed conjunctival epithelial cells and goblet cells in all cases. In vivo confocal microscopy showed disruption of normal layers of the corneal epithelium in all eyes. Confocal images showed cells with characteristics of conjunctival epithelium at the cornea in 76.9% of the total. These findings on confocal microscopy were compatible to limbal stem cell deficiency. Additionally, goblet cells, squamous metaplasia, inflammatory cells and dendritic cells were observed. The sub-basal nerve plexus was not identified in any of the corneas. Corneal neovessels were observed at the epithelium and stroma. All cases showed diffuse hyper-reflective images of the stroma corresponding to opacity of the tissue. CONCLUSIONS: Limbal stem cell deficiency had been confirmed by impression cytology in all cases, and 76.9% of the cases could also be diagnosed by in vivo confocal microscopy through the conjunctival epithelial cell visualization on the corneal surface. Frequent confocal microscopy findings were abnormal cells at the cornea (conjunctival epithelial, goblet and inflammatory cells), corneal neovessels and diffuse hyper-reflection of the stroma. PMID- 24232948 TI - [Progressive subretinal fibrosis: case reports]. AB - The subretinal fibrosis syndrome is a rare disease and is considered part of a group of conditions that are denominated white dots syndrome. However, some authors consider it like a distinct entity from the others diseases with you own features. With these cases we can behold many features already described, like localization and clinical aspect of the lesion, your evolution and the final visual prognosis. It's diagnostic is very important to consider in a varied type of uveitis, because the treatment can avoid the bilateral involvement. PMID- 24232947 TI - Hemorrhagic choroidal detachment after use of anti-glaucomatous eye drops: case report. AB - Eighty-two-year-old patient with a pacemaker using warfarin due to arrhythmia and having an intraocular lens in the right eye, developed spontaneous hemorrhagic choroidal detachment one day after the use of combined preparation of 0.5% timolol maleate and 0.004% travoprost, due to primary open-angle glaucoma. Hemorrhagic detachment was detected by anterior and posterior segment examination, as well as B-scan ultrasonography. After the detachment, excessive increased intraocular pressure was controlled with oral carbonic anhydrase inhibitor, cycloplegic and steroid therapy. After four months, visual acuity was 20/20 and the intraocular pressure was under control with 0.5% timolol maleate and 1% brinzolamide. Controlled reduction of the intraocular pressure should be considered, particularly in older patients under anticoagulant therapy and that had undergone prior ocular surgery. PMID- 24232949 TI - Posterior cortical atrophy--a prototypical case of dementia beginning with visual symptoms: case report. AB - Dementia presenting with prominent higher order visual symptoms may be observed in a range of neurodegenerative conditions and is often challenging to diagnose. We describe a case of progressive dementia presenting with prominent visual cortical symptoms. A 55-year-old, right-handed, woman with early onset of visual impairment not associated with anterior visual pathology, presenting with dyslexia, visual agnosia, Balint's syndrome, and spatial disorientation. Ophthalmologists should consider this condition especially in presenile patients with slowly progressive higher-order visual symptoms. Although described in association with different conditions, it may also occur in Alzheimer disease. PMID- 24232950 TI - Functional impairment with minimal macular damage in femtosecond laser plasma injury: case report. AB - A 26 years old female patient was examined twenty-four hours after observing laser-induced plasma formation in a process of nanoparticle production complaining of bilateral central scotoma. The ophthalmologic evaluation included dilated fundus observation, fluorescein angiography, and optical coherence tomography (OCT). In the first assessment, visual acuity was 20/20 in the right eye and 20/25 in the left eye. Ophthalmologic evaluation revealed colour changes in the macular region of both eyes. Optical coherence tomography showed a central interruption of the photoreceptor layer in both eyes and fluorescein angiography was normal. In subsequent appointments acuity was always 20/20 in both eyes. Abnormal optical coherence tomography findings disappeared in less than 5 months, but subjective complaints of scotoma in the left eye remained. Extra care must be taken in this type of experiment by, for example, reducing the time that the retina is directly exposed to the plasma radiation. PMID- 24232951 TI - Sickle cell retinopathy: diagnosis and treatment. AB - Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients. PMID- 24232952 TI - Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report. PMID- 24232953 TI - Reply: Fibrin-like material in the retinal arterioles and fluorescein angiography findings in Susac syndrome. PMID- 24232954 TI - [Medical communication: history, stories and ABO]. PMID- 24232955 TI - An evaluation of the levels of vitamin d and bone turnover markers after the summer and winter periods in polish professional soccer players. AB - Vitamin D is synthesised in the skin during exposure to sunlight. The fundamental roles of vitamin D are the regulation of calcium and phosphate metabolism and bone mineralisation. Low vitamin D levels in athletes may adversely affect their exercise capabilities. The aim of our study was to investigate changes in serum levels of 25(OH)D3, calcium and bone turnover markers in football players in two training periods differing in the exposure to sunlight (after the summer period and after the winter period). We investigated 24 Polish professional soccer players. Serum levels of the following parameters were determined: 25(OH)D3, calcium, osteocalcin (OC), parathormone (PTH), procollagen type I N - terminal peptide (P1NP), and beta - CrossLaps (beta - CTx). We showed significantly higher levels of 25(OH)D3 and calcium and lower levels of PTH after the summer period versus the winter period. No significant differences in the levels of bone turnover markers were found. Furthermore, we did not observe any significant correlations between the levels of 25(OH)D3 and other parameters. Normal levels of 25(OH)D3 were observed in 50% of the players after the summer period and only in 16.7% of the players after the winter period. It is justified to measure the levels of 25(OH)D3, calcium and PTH in soccer players, especially after the winter period, when the exposure to sunlight is limited. PMID- 24232956 TI - A self-assembled microbonded germanium/silicon heterojunction photodiode for 25 Gb/s high-speed optical interconnects. AB - A novel technique using surface tension to locally bond germanium (Ge) on silicon (Si) is presented for fabricating high performance Ge/Si photodiodes. Surface tension is a cohesive force among liquid molecules that tends to bring contiguous objects in contact to maintain a minimum surface energy. We take advantage of this phenomenon to fabricate a heterojunction optoelectronic device where the lattice constants of joined semiconductors are different. A high-speed Ge/Si heterojunction waveguide photodiode is presented by microbonding a beam-shaped Ge, first grown by rapid-melt-growth (RMG) method, on top of a Si waveguide via surface tension. Excellent device performances such as an operating bandwidth of 17 GHz and a responsivity of 0.66 and 0.70 A/W at the reverse bias of -4 and -6 V, respectively, are demonstrated. This technique can be simply implemented via modern complementary metal-oxide-semiconductor (CMOS) fabrication technologies for integrating Ge on Si devices. PMID- 24232957 TI - Sieve-element differentiation and fluoresceine translocation in wound-phloem of pea roots after complete severance of the stele. AB - Experimental interruption of the root stele of Pisum sativum L. induces in the cortex tissue the development of wound-sieve tubes which bridge the wound and reconnect the vascular stumps. Outside the stele, sieve plates arise from primary pit fields. This origin is confirmed by the distribution of future sieve pores over the original parenchyma cell wall and by remnants of the pitfield cavity in developing sieve plates. Differentiation of wound-sieve elements is similar to that of bundle-sieve elements and includes the chromatolytic disintegration of nuclei as well as the development of typical sieve pores arising from pit-field plasmodesmata. The completion of first woundsieve tubes (indicated by a continuous chain of anilin-blue-positive sieve plates by-passing the wound) was observed 55-62 h after wounding. However, effective translocation, visualized with fluoresceine as a phloem-mobile marker, was not found until 10 h (on average) later. It is suggested that this time delay corresponds to the maturing of the last link within a chain of wound-sieve-tube members. Presumably, enucleate sieve elements with widened pores are a prerequisite for effective phloem translocation. PMID- 24232958 TI - Cotyledonal chloroplasts in the hypogeal seeds of clementine. AB - Clementine (Citrus nobilisxCitrus aurantium amara pumila) is a chloroembryophyte with green quiescent embryos and hypogeal germination. The cotyledonal chloroplasts have been studied during germination in the dark and under two different irradiances 120 and 240 MUmol.m(-2).s(-1) throughout a period of three weeks. The plastids of the outer adaxial and inner regions develop differently. In the light, the former differentiate a photosynthetically active thylakoid system with an ultrastructural organization and a polypeptide composition resembling that of leaf chloroplasts. The "inner" chloroplasts maintain an organization reminiscent of chloroplasts of the quiescent embryo and never get beyond the photosynthesis/respiration compensation point; their differentiation pattern appears essentially the same under the two different irradiances. These observations and the germination in the dark indicate that the above differentiation is not strictly photodependent. The greening ability of the cotyledons provides, on occasion, an additional photosynthetic supply to this plant. PMID- 24232959 TI - Selection of a universal hybridizer in Sinapis turgida Del. and regeneration of plantlets from somatic hybrids with Brassica species. AB - A double-mutant cell line, which was unable to grow in a medium with NO 3 (-) as the sole nitrogen source and was resistant to 5-methyl-tryptophan (5MT), was selected from cell suspensions of Sinapis turgida Del. (Brassicaceae) by culturing the cells in AA medium (Toriyama and Hinata, 1985, Plant Sci. 41, 179 183) supplemented with 50 mM chlorate and 229 MUM 5MT. Protoplasts of this cell line were fused with mesophyll protoplasts of Brassica oleracea L. with dextran, and six somatic hybrids were selected initially by culture in the NO 3 (-) medium and then by transfer to the NO 3 (-) medium supplemented with 229 MUM 5MT. The somatic hybrids produced embryoids, leaves and plantlets on a regeneration medium. The hybrid characters were confirmed by investigations of acid phosphatase (EC 3.1.3.2) and peroxidase (EC 1.11.1.7) isoenzymes, chromosome number, growth on NO 3 (-) medium, 5MT resistance, and capacity to regenerate plants. Somatic hybrids between S. turgida Del. and B. nigra (L.) Koch were also obtained using this method. These results indicate that the double-mutant cell line established here will be able to serve as a universal hybridizer to select somatic hybrids after protoplast fusion with any other wild-type partner. PMID- 24232960 TI - Composition and properties of the sexual agglutinins of the flagellated green alga Chlamydomonas eugametos. AB - Sexual interaction between gametes of opposite mating type (mt) of the unicellular green alga Chlamydomonas eugametos starts with agglutination of the cells via particular glycoproteins on the flagellar surface. Purification of these socalled agglutinins was achieved by a three-step procedure consisting of, successively, gel filtration, anion-exchange chromatography, and high-performance gel filtration. The amino-acid and sugar compositions of both agglutinins showed a high degree of similarity; the most prominent amino acids were hydroxyproline, serine and glycine, and the main sugars were arabinose and galactose. The carbohydrate portions represented about half of the molecular mass of both agglutinins. Using high-performance gel filtration, a calibration curve was constructed for high-molecular-mass compounds from which the Stokes' radius of the sexual agglutinins could be estimated. The mt (+) agglutinin had a Stokes' radius of 39 nm and a sedimentation coefficient of 9.3 S. From these data its molecular mass was estimated to be 1.2.10(6). The corresponding data for the mt ( ) agglutinin were 38 nm, 9.7 S and 1.3.10(6), respectively. The biological activity of both agglutinins was destroyed by mild periodate treatment. Treatment with specific glycosidases had a differential effect on the biological activity of the agglutinins. These observations indicate that carbohydrate side-chains are needed for biological activity and perhaps are responsible for the specifity of the sexual agglutinins. A comparison of both agglutinins is given and their possible structure is discussed in relation to their amino-acid and sugar compositions. PMID- 24232961 TI - Occurrence of O-methylated sugars in surface glycoconjugates in Chlamydomonas eugametos. AB - Previously, we have shown that the monomeric-sugar composition of cell-surface associated glycoconjugates of two strains of Chlamydomonas eugametos, of different mating type, differs strikingly (Gerwig et al. 1984, Carbohydr. Res. 127, 245-251). Besides the common occurrence of various pentoses and hexoses, the glycoconjugates of one strain contain 4-O-methyl xylose, a 2-O-methyl pentose (probably 2-O-methyl arabinose) and 3-O-methyl galactose, whereas those of the other strain contain 6-O-methyl mannose and 3-O-methyl glucose. In order to investigate whether these differences are relevant to the mating process of this organism, the sugar composition of the sexual progeny of these strains was analyzed. The ability to produce 4-O-methyl xylose, 2-O-methyl pentose and 3-O methyl galactose on the one hand, and the ability to produce 6-O-methyl mannose and 3-O-methyl glucose on the other hand, appear to be genetically linked. However, the ability to produce either set of O-methyl sugars was inherited independently of mating type. O-Methylated sugars do not occur in the cell wall of C. eugametos, or in the cell-free medium, but only in surface-membrane associated glycoconjugates, extractable with salt or detergent solutions. PMID- 24232962 TI - Monoclonal antibodies to surface glycoconjugates in Chlamydomonas eugametos recognize strain-specific O-methyl sugars. AB - Monoclonal antibodies are described that are directed against cell surface components of the unicellular green alga Chlamydomonas eugametos. These antibodies recognize strain-specific epitopes which occur at the surface of vegetative and gametic cells. Two different groups of epitopes are distinguished that are never detectable together in one clonal cell culture. Evidence is presented showing that the antigenicity of cell surface molecules is a consequence of the presence of particular O-methylated sugars. Monoclonal antibodies reacting with one group of epitopes were studied in more detail, and immunoprecipitation and Western-blot studies showed that these epitopes can be arranged into four classes. The use of these monoclonal antibodies as strain specific markers in light- and electron-microscopical techniques is illustrated. PMID- 24232963 TI - The influence of atmospheric humidity on leaf expansion in Beta vulgaris L. AB - Humidity effects on leaf expansion in sugar beets (Beta vulgaris L.) were explored using linear variable differential transducers. In continuous light, an increase in relative humidity (RH) from 35 to 61 or 75% resulted in a rapid increase in leaf extension which was maintained for 10-15 min before slowing down. Increasing RH from 35 to 85% increased leaf-extension rate (LER) in light and in dark and substantially diminished the ratio of dark LER to light LER, showing that high humidity can offset the reduction in LER which occurs on illumination. Episodes of irradiance with visible or infrared radiation resulted in diminished LER, indicating that increases in transpiration may reduce the flux of water available for leaf cell expansion. The hypothesis that leaf area expansion in sugarbeet may be controlled by the expansion of the leaf epidermis is discussed. PMID- 24232964 TI - Purification of an endopeptidase involved with storage-protein degradation in Phaseolus vulgaris L. cotyledons. AB - Phaseolin, the major seed storage protein of Phaseolus vulgaris L., is degraded in the cotyledons in the first 7-10 d following seed germination. We assayed cotyledon extracts for protease activity by using [(3)H]phaseolin as a substrate and then fractionated the digestion mixtures by sodium dodecyl sulfate polyacrylamide gel electrophoresis in order to identify the cleavage products. The cotyledons of 4-d-old seedlings contain an endopeptidase which cleaves the polypeptides of [(3)H]phaseolin (apparent molecular weights=51 000, 48 000, 46 000 and 43 000) into three discrete clusters of proteolytic fragments (M rs=27 000, 25 000 and 23 000). Endopeptidase activity is not detected in the cotyledons until the protein content of these organs starts to decline, shortly after the first day of seedling growth. Endopeptidase activity increases to a maximum level in the cotyledons of 5-d-old seedlings and then declines to a minimum value by day 10. The enzyme was purified 335-fold by ammonium-sulfate precipitation, organomercurial-agarose chromatography, gel filtration and ion-exchange chromatography. The endopeptidase constitutes 0.3% of the protein content in the cotyledons of 4-d-old seedlings. It is a cysteine protease with a single polypeptide chain (M r=30 000). Optimum hydrolysis of [(3)H]phaseolin occurs at pH 5. The enzyme is irreversibly inactivated at pH values above 7 and at temperatures above 45 degrees C. The endopeptidase attacks only a limited number of peptide bonds in [(3)H]phaseolin, without causing any appreciable change in the native molecular weight of the storage protein. The endopeptidase is also able to hydrolyze the bean-seed lectin, phytohemagglutinin. Thus, this enzyme may play a general role in degrading cotyledon proteins of P. vulgaris following seed germination. PMID- 24232965 TI - The regulation of turgor pressure during sucrose mobilisation and salt accumulation by excised storage-root tissue of red beet. AB - The changes in turgor pressure that accompany the mobilisation of sucrose and accumulation of salts by excised disks of storage-root tissue of red beet (Beta vulgaris L.) have been investigated. Disks were washed in solutions containing mannitol until all of their sucrose had disappeared and then were transferred to solutions containing 5 mol.m(-3) KCl+5 mol.m(-3) NaCl in addition to the mannitol. Changes in solute contents, osmotic pressure and turgor pressure (measured with a pressure probe) were followed. As sucrose disappeared from the tissue, reducing sugars were accumulated. For disks in 200 mol.m(-3) mannitol, the final reducing-sugar concentration equalled the initial sucrose concentration so there was no change in osmotic pressure or turgor pressure. At lower mannitol concentrations, there was a decrease in tissue osmotic pressure which was caused by a turgor-driven leakage of solutes. At concentrations of mannitol greater than 200 mol.m(-3), osmotic pressure and turgor pressure increased because reducing sugar accumulation exceeded the initial sucrose concentration. When salts were provided they were absorbed by the tissue and reducing-sugar concentrations fell. This indicated that salts were replacing sugars in the vacuole and releasing them for metabolism. The changes in salf and sugar concentrations were not equal because there was an increase in osmotic pressure and turgor pressure. The amount of salt absorbed was not affected by the external mannitol concentration, indicating that turgor pressure did not affect this process. The implications of the results for the control of turgor pressure during the mobilisation of vacuolar sucrose are discussed. PMID- 24232966 TI - Correlation between thylakoid protein phosphorylation and molecular organization of the photosynthetic apparatus in a dynamic system. AB - In-vitro thylakoid protein phosphorylation has been studied in synchronized cells of Scenedesmus obliquus at the 8- and 16-h of the life cycle, stages which are characterized by the maximum and minimum photosynthetic activities, respectively. The stage of maximum photosynthetic activity (8-h) is characterized by the highest protein phosphorylation in vitro and in vivo, by the largest proportion of the heavy subfraction of thylakoids, and by maximum oligomerization of the light-harvesting chlorophyll a/b-protein complex, altogether creating the highest energy charge of the thylakoid membranes. Protein phosphorylation in vitro decreases the amount of the heavy subfraction and increases the amount of oligomerization of the antenna of photosystem I (PSI) (increase of chlorophyll b in the light fraction). Concomittantly, PSII units become smaller (longer time for the rise in fluorescence induction) and photosynthetic efficiency increases (decrease of fluorescence yield). In-vivo protein phosphorylation is controlled mainly endogenously during the 8-h of the life cycle but is exogenously modulated by light to optimize the photosynthetic activity by redistribution of pigment protein complexes. In-vitro protein phosphorylation seems to restore partially the conditions prevalent in vivo and lost during the preparation of membranes. The effect is greater in 16-h cells which have less-stable membranes. The regulatory mechanism between membrane stabilization and oligomerization on the one hand and redistribution of the light-harvesting chlorophyll a/b-protein complex from PSII to PSI on the other hand remains unexplained. We have confirmed that the mechanism of protein phosphorylation is regulated via plastohydroquinone, but experiments with the plastohydroquinone analogue 2,3,5,6 tetramethyl-p-benzoquinone demonstrated that plastohydroquinone is not solely responsible for the differences in protein phosphorylation of 8- and 16-h thylakoids. The inhibitory effect of ADP and the distinct rates of kinase reaction indicate that the adenylate energy charge and changes in the organization of the photosynthetic apparatus also contribute to the observed differences in protein phosphorylation. Phosphorylation in the presence of 3 (3',4'-dichlorophenyl)-1,1-dimethylurea indicated that the 32-kDa phosphoprotein and the herbicide-binding QB protein may be the same. These experiments also indicated that 3-(3',4'-dichlorophenyl)-1,1-dimethylurea-binding reduces kinase activity directly and not only by inhibiting electron transport. PMID- 24232967 TI - Effect of cytokinins on ribosomal RNA gene expression in excised cotyledons of Cucurbita pepo L. AB - Excised pumpkin (Cucurbita pepo L.) cotyledons were used to investigate the effects of two different types of cytokinins: N(6)-benzyladenine and N1-(2-chloro 4-pyridyl)-N2-phenylurea on RNA synthesis in isolated nuclei. Treatment of cotyledons with both cytokinins resulted in a rapid enhancement of nuclear RNA polymerase-I activity (EC 2.7.7.6). Maximum stimulation of RNA polymerase I, responsible for rRNA synthesis, was observed 4-6 h after the start of cytokinin action. The activity of RNA polymerase II was stimulated much more slowly and to a lesser extent. Uridine 5'-monophosphate-uridine analysis of the alkalidigested nascent pre-rRNA chains showed that the stimulation of RNA-polymerase-I activity was the consequence of an increase of the polyribonucleotide-clongation rate. No significant change in the number of transcribing enzyme molecules was defected after hormone treatment (86.10(3) RNA-polymerase-I molecules per diploid genome).Indications that de-novo protein synthesis is necessary for cytokinin mediated RNA-polymerase stimulation were derived from experiments showing inhibition by cycloheximide. PMID- 24232968 TI - Long-term acid-induced wall extension in an in-vitro system. AB - When frozen-thawed Avena sativa L. coleoptile and Cucumis sativa L. hypocotyl sections, under tension, are acid-treated, they undergo rapid elongation (acid extension). The acid-extension response consists of two concurrent phases: a burst of extension which decays exponentially over 1-2 h (ExE), and a constant rate of extension (CE) which can persist for at least 6 h. The extension (AL) is closely represented by the equation: DeltaL = a - a . e (kt) + c . t where a is the total extension of the exponential phase, k is the rate constant for ExE, and c is the rate of linear extension (CE). Low pH and high tension increased a and c, whereas temperature influenced k. The magnitude of the CE (over 50% extension/10 h), the similarity in its time course to auxin-induced growth, and the apparent yield threshold for CE indicate that CE is more likely than ExE to be the type of extension which cell walls undergo during normal auxin-induced growth. PMID- 24232969 TI - Ribulose-1,5-bisphosphate carboxylase/oxygenase expression in melon plants infected with Colletotrichum lagenarium : Activity, content and rate of synthesis. AB - Ribulose-1,5-bisphosphate carboxylase/oxygelase (RuBPCase) was studied in melon leaves infected by Colletotrichum lagenarium, a fungal pathogen of melons. Electrophoretic analysis of melon leaf proteins indicated a strong effect of infection on RuBPCase, the subunits of which gradually disappeared during the different stages of infection. Enzyme activity also declined 4 d after inoculation and its content, measured by immunoelectrophoresis, decreased to a similar extent. Synthesis of the large and small subunits of RuBPCase was followed by in-vivo pulse-labeling experiments. A drastic decrease in the rate of RuBPCase-subunit synthesis occurred 3 d after inoculation and preceded the appearance of disease symptoms. There was an apparent coordination of the synthesis of the two subunits under these conditions. PMID- 24232970 TI - Transcription and translation of phloem protein (PP2) during phloem differentiation in Cucurbita maxima. AB - The synthesis of a major phloem protein, PP2, was investigated by measurement of the mRNA at various stages of phloem development in Cucurbita. Quantitative assays with immuno-electrophoresis showed that the amounts of PP2 in hypocotyls of Cucurbita seedlings increased with the age of seedlings. An increase in mRNA for PP2 during the early stages of seedling growth was also observed by immunoprecipitation of the invitro translation products of hypocotyl polyadenylated RNA. There was close timing in the variations of PP2 synthesised in vivo and in the changes in amounts of translatable PP2-mRNA during the course of seedling growth. A complementary-DNA (cDNA) library to polyadenylated RNA from hypocotyls of 3-d-old Cucurbita seedlings has been constructed. Two cDNA clones, A and B, have been identified by hybrid-release translation to be complementary to the mRNA coding for PP2. The levels of total mRNA for PP2 measured with clone A were found to increase in the first 4 d of seedling growth but decreased to lower levels in older seedlings. Regulatory controls on both transcription and modification of transcripts appeared to occur during the synthesis of PP2. PMID- 24232971 TI - Time course of competence in phytochrome-controlled appearance of nuclear-encoded plastidic proteins and messenger RNAs. AB - The phytochrome-controlled expression of genes coding for plastidic proteins was studied in mustard (Sinapis alba L.) seedling cotyledons in continuous red (R) and far-red (FR) light, i.e. under steady-state conditions with regard to phytochrome, and in darkness over a time span of 8 d after sowing (25 degrees C). (i) The time courses of the levels of the Calvin-cycle enzymes ribulose-1,5 bisphosphate carboxylase (RuBPCase) and NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (NADP-GPD) were found to be optimum curves. The time at which the optimum (peak) occurred was - independent of fluence rate - the same in R (strong phytochrome action, chlorophyll accumulation and photosynthesis) and FR (strong phytochrome action but no significant chlorophyll accumulation and no photosynthesis). The starting point (first detectable inccrease of enzyme level) was also endogenously fixed and not affected by light. However, the two enzymes differed insofar as the peak was at 4 d after sowing for RuBPCase activity and 4.5 d for GPD. Western blots of the small (SSU) and large (LSU) subunits of RuBPCase showed that enzyme activity and protein levels were correlated. It was concluded that a dramatic change of competence towards phytochrome had occurred and that this change was endogenous. This conclusion was confirmed by short-term induction experiments. In constant darkness (D) the low enzyme levels were saturation rather than optimum curves, presumably because enzyme turnover was lacking. (ii) The time course of accumulation of membrane components showed that chlorophyll and LHCP (light-harvesting chlorophyll a/b-binding protein of photosystem II) levels were closely correlated in R until 6 d after sowing. Thereafter the levels remained constant. The accumulation of membrane components was not related to the accumulation of Calvin-cycle enzymes. (iii) Time courses of the levels of translatable mRNAs, particularly SSU mRNA and LHCP mRNA were determined. In the case of SSU the maximum mRNA-level was found in R, FR and D around 3 d. This was compatible with the in-situ protein accumulation rate. Induction experiments with FR showed that accumulation of SSU mRNA followed the same rise and fall (peak at 3 d) as would be expected from the time course of mRNA levels and from enzyme-induction experiments. In the case of LHCP mRNA the peak was between 3 and 4 d in R, and was not well correlated with in-situ protein accumulation. Translatable LHCP mRNA was also formed in FR and in D-with a peak between 3 and 4 d-although LHCP protein was not detectable under these circumstances (because of the lack of chlorophyll). The data indicate that competence of gene expression towards phytochrome is determined endogenously. However, in the case of LHCP its appearance is not only limited by mRNA but also depends on the availability of chlorophyll. PMID- 24232972 TI - Persistent circadian rhythms in the phosphorylation state of phosphoenolpyruvate carboxylase from Bryophyllum fedtschenkoi leaves and in its sensitivity to inhibition by malate. AB - Phosphoenolpyruvate carboxylase (EC 4.1.1.31; PEPCase) from Bryophyllum fedtschenkoi leaves has previously been shown to exist in two forms in vivo. During the night the enzyme is phosphorylated and relatively insensitive to feedback inhibition by malate whereas during the day the enzyme is dephosphorylated and more sensitive to inhibition by malate. These properties of PEPCase have now been investigated in leaves maintained under constant conditions of temperature and lighting. When leaves were maintained in continuous darkness and CO2-free air at 15 degrees C, PEPCase exhibited a persistent circadian rhythm of interconversion between the two forms. There was a good correlation between periods during which the leaves were fixing respiratory CO2 and periods during which PEPCase was in the form normally observed at night. When leaves were maintained in continuous light and normal air at 15 degrees C, starting at the end of a night or the end of a day, a circadian rhythm of net uptake of CO2 was observed. Only when these constant conditions were applied at the end of a day was a circadian rhythm of interconversions between the two forms of PEPCase observed and the rhythms of enzyme interconversion and CO2 uptake did not correlate in phase or period. PMID- 24232973 TI - The control of chloroplast number in wheat mesophyll cells. AB - Chloroplast number per cell and mesophyll cell plan area were determined in populations of separated cells from the primary leaves of different wheat species representing three levels of ploidy. Mean chloroplast number per cell increases with ploidy level as mean cell size increases. But in addition the analysis of individual cells clearly shows that cells of a similar size but from species of different ploidies have similar numbers of chloroplasts. We conclude that the number of chloroplasts within a cell is closely correlated (P<0.001) with the size of the cell and this relationship is consistent for species of different ploidies over a wide range of cell sizes. These results are discussed in relation to the hypothesis that chloroplast number in leaf mesophyll cells is determined by the size of the cell. PMID- 24232974 TI - Leaf anatomy, water relations and crassulacean acid metabolism in the chlorenchyma and colourless internal water-storage tissue of Carpobrotus edulis and Senecio ?mandraliscae. AB - Both Carpobrotus edulis and Senecio ?mandraliscae possess leaves with a peripheral chlorenchyma and colourless internal water-storage tissue. Water stress in C. edulis growing under semi-natural conditions resulted in the induction of weak Crassulacean acid metabolism (CAM) whereas well-watered plants of S. ?mandraliscae exhibited a similar degree of CAM. Titratable acidity in the separated water-storage tissue was substantially lower than in the chlorenchyma in both species but, nevertheless, increased during the night and decreased during the day either when sampled from the intact plant or from incubated tissue slices. Indeed, the increase in nocturnal titratable acidity produced by the water-storage tissue in situ accounted for approx. 30% of total acidification on a per-leaf basis. It appears that during the night the water-storage tissue in these species is able to fix CO2 which is subsequently released during the day to enter the photosynthetic carbon-reduction cycle of the chlorenchyma. Diurnal rhythms of water potential (Psi) and osmotic potential (Psis) were measured in separated chlorenchyma and water-storage tissue by thermocouple psychrometry. Both parameters increased during the latter part of the daytime and initial nocturnal period and decreased during the rest of the night and into the post dawn period. The chlorenchyma of water-stressed plants of C. edulis appeared to possess a marked negative turgor pressure (as determined from Psi-Psis) but this was caused by a severe underestimation in the measurement of the chlorenchyma Psi. It is suggested that this artefact arose from release of colloidal polysaccharide mucilage, or possibly tannins, from broken tannin cells producing a lowering of water activity when measured using thermocouple psychrometry. PMID- 24232975 TI - Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study. AB - AIMS/HYPOTHESIS: The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk. METHODS: A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models. RESULTS: During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m2 (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p trend < 0.0001 and p trend = 0.03, respectively). The NEAP score provided similar findings. CONCLUSIONS/INTERPRETATION: We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms. PMID- 24232976 TI - Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference. AB - Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14-20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a 'kinesthetic' mechanism for UM and a 'visual imagery' mechanism for BM tapping movement. PMID- 24232977 TI - Diagnosis, management, and long-term outcomes of rectovaginal endometriosis. AB - Rectovaginal endometriosis is the most severe form of endometriosis. Clinically, it presents with a number of symptoms including chronic pelvic pain, dysmenorrhea, deep dyspareunia, dyschezia, and rectal bleeding. The gold standard for diagnosis is laparoscopy with histological confirmation; however, there are a number of options for presurgical diagnosis, including clinical examination, transvaginal/transrectal ultrasound, magnetic resonance imagining, colonoscopy, and computed tomography colonography. Treatment can be medical or surgical. Medical therapies include birth control pills, oral progestins, gonadotropin releasing hormone agonists, danazol, and injectable progestins. Analgesics are often used as well. Surgery improves up to 70% of symptoms. Surgery is either ablative or excisional, and is conducted via transvaginal, laparoscopic, laparotomy, or combined approaches. Common surgical techniques involve shaving of the superficial rectal lesion, laparoscopic anterior discoid resection, and low anterior bowel resection and reanastomosis. Outcomes are generally favorable, but postoperative complications may include intra-abdominal bleeding, anastomotic leaks, rectovaginal fistulas, strictures, chronic constipation, and the need for reoperation. Recurrence of rectal endometriosis is a possibility as well. Other outcomes are improved pain-related symptoms and fertility. Long-term outcomes vary according to the management strategy used. This review will provide the most recent approaches and techniques for the diagnosis and treatment of rectovaginal endometriosis. PMID- 24232978 TI - Fractional exhaled nitric oxide in the interpretation of specific inhalational challenge tests for occupational asthma. AB - PURPOSE: Fractional exhaled nitric oxide (FENO) measurements are recommended for the assessment of eosinophilic airway inflammation in asthma. Clinically relevant increases in FENO have been reported 24 h after positive specific inhalational challenge (SIC) tests in occupational asthma. We aimed to determine whether positive SICs could be discriminated from control tests, on the basis of change in FENO. METHODS: We reviewed all positive SICs to a variety of agents performed at our institution 2008-2012 and gathered data on age, sex, asthmatic response (immediate/dual/late), smoking status, inhaled corticosteroid usage, and FENO pre and 24-h postcontrol and positive SIC from each worker. Changes in FENO after positive SICs were compared with control SICs from each worker, by using paired Student's t tests. RESULTS: In 16 workers, negative control challenges were associated with mean changes in FENO of 9 % (95 % CI -1.14 to 19.01) or 1.1 ppb (95 % CI -3.59 to 5.84); 2 of 16 (13 %) workers tested showed increases in FENO that were clinically relevant based on recent guidelines. Subsequent positive SICs were associated with mean changes in FENO of 7 % (95 % CI -15.73 to 29.6) or 2.1 ppb (95 % CI -6.07 to 10.19), which were not significantly different to controls; only 2 of 16 (13 %) workers had FENO changes that were clinically relevant. CONCLUSIONS: FENO changes above the upper confidence limits of >=20 % or >=6 ppb may be considered to be outside the range of normality. However, the majority of workers who had clearly positive SICs to common low molecular weight agents also had no statistically or clinically relevant increase in FENO. Therefore, change in FENO does not predict a positive SIC in this group. PMID- 24232979 TI - Chronic cough and OSA: an underappreciated relationship. AB - Chronic cough is increasingly being recognized as a process that has multiple initiating and perpetuating triggers. Obstructive sleep apnea has recently emerged as a possible disease that can lead to chronic cough. This review details the available clinical evidence that links these two disparate diseases and explores mechanistic bases of their relationship. PMID- 24232980 TI - Cement Removal from the Femur Using the ROBODOC System in Revision Total Hip Arthroplasty. AB - Introduction. The perforation and fracture of the femur during the removal of bone cement in revision total hip arthroplasty (THA) are serious complications. The ROBODOC system has been designed to selectively remove bone cement from the femoral canal, but results have not been reported yet. The purpose of our study was to evaluate the clinical and radiographic results of revision THA using the ROBODOC system for cement removal. Materials and Methods. The subjects comprised 19 patients who underwent revision THA using the ROBODOC system. The minimum duration of follow-up was 76 months (median, 109 months; range, 76-150 months). The extent of remaining bone cement on postoperative radiography, timing of weight bearing, and the complications were evaluated. Results. The mean Merle d'Aubigne and Postel score increased from 10 points preoperatively to 14 points by final follow-up. Bone cement was completely removed in all cases. Full weight bearing was possible within 1 week after surgery in 9 of the 19 cases and within 2 months in all remaining cases. No instances of perforation or fracture of the femur were encountered. Conclusions. Bone cement could be safely removed using the ROBODOC system, and no serious complications occurred. Full weight bearing was achieved early in the postoperative course because of circumferential preservation of the femoral cortex. PMID- 24232981 TI - Application of sodium nitroprusside results in distinct antioxidant gene expression patterns in leaves of mature and senescing Medicago truncatula plants. AB - Sodium nitroprusside (SNP) represents one of the most commonly used NO donors in biological sciences, which acts as a signal molecule in plants responsible for the regulation of the expression of many defense-related enzymes. This study attempts to provide novel insight into the effect of application of low (100 MUMU) and high (2.5 mM) concentrations of SNP on antioxidant gene expression (cAPX, GST, FeSOD, CAT, and AOX) in mature (40 day) and senescing (65 day) Medicago truncatula plants. Quantitative real-time RT-PCR suggests that low concentration of SNP applied in mature leaves leads to an overall induction of antioxidant gene expression, while increasing concentration results in suppression of these genes. Conversely, older plants demonstrate a much more variable regulation which appears to be time dependent. The observed transcriptional regulation pattern in mature M. truncatula plants comes in support of the previously documented protective or damaging effect of SNP depending on concentration applied, whereas senescing M. truncatula plants demonstrated a general suppression in antioxidant gene expression levels regardless of SNP concentration, indicative of reduced overall plant defense capacity against free radicals. PMID- 24232983 TI - Genetic transformation of willows (Salix spp.) byAgrobacterium tumefaciens. AB - Anin vitro transformation method has been developed for stem explants of fast growing willow clones (Salix spp.) usingAgrobacterium tumefaciens as a vector. Transformants obtained with the strains C58 and GV3101 (pGV3851::pLD1) were selected on hormone-free medium and on medium containing kanamycin, respectively. Transformation was confirmed by Southern blot analysis and nopaline assay. Inoculation of green-house grown plants with nopaline and octopine wildtype strains and shoot or root inducing mutant strains caused undifferentiated tumors at a frequency of 0 to 80%, depending on theSalix genotype and the bacterial strain used. PMID- 24232982 TI - Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL. AB - BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL), which are the two most common types of gastric lymphomas, have different clinicopathological features and molecular characteristics with distinct clinical outcomes. Tumor suppressor miR-34a connects the p53 network with forkhead box protein 1 (FOXP1) and BCL2. Here, we investigated the prognostic value of these molecules in gastric MALT lymphoma and DLBCL for use in routine clinical practice. METHODS: Relative miR-34a expression was detected by quantitative reverse transcriptase-polymerase chain reaction in 20 cases of MALT lymphomas and 20 cases of DLBCLs. Tissue microarray, in situ hybridization, and immunohistochemistry analysis were used to examine the expression of miR-34a and its regulated genes, FOXP1, p53, and BCL2 proteins, in 64 patients with gastric MALT lymphoma and in 58 patients with DLBCL. Helicobacter pylori infection, overall survival (OS), and progression-free survival (PFS) were documented. RESULTS: The expression level of miR-34a was markedly decreased in MALT lymphomas and DLBCLs compared to normal gastric tissues and peripheral blood mononuclear cells. miR-34a was present in the cytoplasm and nucleus of lymphocytes. Its expression was significantly downregulated in MALT and DLBCL lymphoma tissues, as compared with normal lymphocytes. The expression level of miR-34a in DLBCL was lower than in MALT lymphoma. FOXP1 was found to be positive in 48%, p53 in 20%, and BCL2 in 68% of MALT lymphoma cases. The corresponding positive rates of these markers in DLBCL were 64, 57, and 52%, respectively. High expression of FOXP1, p53, and BCL2 was seen in stage III and IV of both types of lymphomas. FOXP1, p53, and BCL2 positivity was associated with poor OS with both lymphoma types but OS with DLBCL was significantly lower than with MALT lymphoma. CONCLUSIONS: Decreased miR-34a expression and increased FOXP1, p53, and BCL2 coexpression to predict a poor OS for MALT lymphoma and DLBCL patients could become very important prognostic markers in daily clinical work. Further investigation of these changes may be of prognostic significance in clinical practice. PMID- 24232984 TI - Chromosomal localization of parsley 4-coumarate: CoA ligase genes by in situ hybridization with a complementary DNA. AB - A near full-length cDNA (1.9 kb) was used as probe forin situ hybridization to assign one of the two highly homologous 4-coumarate: CoA ligase genes in parsley (Petroselinum crispum) to the short arm of a submetacentric chromosome. The results suggest, but do not definitely prove, that the second gene is located on a metacentric chromosome and is thus unlinked from the other. PMID- 24232985 TI - Genetic transformation ofCatharanthus roseus G. Don byAgrobacterium rhizogenes. AB - Catharanthus roseus plantlets were inoculated with differentAgrobacterium rhizogenes strains. This plant species is known to produce secondary metabolites and axenic hairy-root cultures are an alternative to extraction of plant tissue for the compounds which are synthesized in roots. Hairy root lines were established from inoculations with the agropine strain 15834 and transformed plants were obtained after spontaneous regeneration. Phenotypic alterations of both the root system and the aerial parts were observed in transformed plants. All the tissues analyzed contained agropine and mannopine. T-DNA analysis confirmed the presence of TL- and TR-DNAs either as distinct inserts, or as a single and continuous insert including the region between TL and TR on pRi 15834. PMID- 24232986 TI - Isozymes as biochemical and cytochemical markers in embryogenic callus cultures of maize (Zea mays L.). AB - Isozyme analyses were carried out on protein extracts of non-embryogenic and embryogenic callus fromZea mays L., using polyacrylamide gel electrophoresis. We examined the isozyme patterns of glutamate dehydrogenase, peroxidase and acid phosphatase for their utility as biochemical markers of maize embryogenic callus cultures. These isozyme systems were also used to examine possible correlations between isozymes and different stages of regeneration. The zymograms of peroxidase and glutamate dehydrogenase differed for non-embryogenic and embryogenic callus. Further, some isozymes were correlated with the morphological appearance of the tissue while others seemed to be involved with the duration of the culture period. Using the same enzyme assays on fresh tissue samples we were able to test the three enzymes as cytochemical markers in embryogenic cultures. Glutamate dehydrogenase proved to be most successful to discriminate embryogenic from non-embryogenic cells. PMID- 24232987 TI - Stable transformation of sugarbeet protoplasts by electroporation. AB - Conditions were optimized for the culture, antibiotic selection and stable transformation by electroporation of suspension culture protoplasts of sugarbeet,Beta vulgaris L.. Highest plating efficiencies (up to 65% at day 21) were obtained if protoplasts were cultured in PGO salts (de Greef and Jacobs, 1979) supplemented with 0.1 mg/1 2,4-D, 0.01 mg/l BAP and 9% mannitol, and in 0.6% agarose rather than in liquid medium. Sensitivity to kanamycin also depended on whether protoplasts were cultured in liquid or agarose medium. Stable transformation of protoplast-derived colonies, as determined by resistance to kanamycin and Southern blot analysis, was achieved by electroporation using both rectangular and exponentially-decaying pulses. PMID- 24232988 TI - High-yield production of tropane alkaloids by hairy-root cultures of aDatura candida hybrid. AB - Hairy root cultures were obtained following inoculation of the stems of sterile plantlets of aDatura candida hybrid withAgrobacterium rhizogenes. The scopolamine and hyoscyamine content was quantified by HPLC and compared with the non transformed plants. The alkaloid yield (0.68% dry weight) obtained with the hairy roots was 1.6 and 2.6 times the amount found in the aerial parts and in the roots of the parent plants, respectively. Only a small proportion of alkaloids was released into the growth medium. Scopclamine was the principal alkaloid and the scopolamine/hyoscyamine ratio of ca. 5:1 makes these hairy roct cultures worthy of consideration as a source of scopolamine. PMID- 24232989 TI - Production of doubled haploid lines in frequencies sufficient for barley breeding programs. AB - Winter barley (Hordeum vulgare L.) anthers were cultured on different liquid and on starch-solidified media. The optimal embryo and callus formation with different F1-lines and the cv. 'Igri' was obtained on a liquid medium with 20% Ficoll, 20 g/l maltose and barley starch. But the influence of the growth conditions of the donor plants and the genotypical differences are still enormous. The procedure has been optimized to such an extent that it can be used economically. PMID- 24232990 TI - Chromosome elimination and mutation in tetraploid somatic hybrids ofSolanum tuberosum andSolanum phureja. AB - The hybridity of eleven somatic hybrids between a diploidS. tuberosum and a diploidS. phureja clone could be verified because the parent karyotypes differed in their C-banding patterns. The hybrids were hypotetraploid and some carried structurally rearranged chromosomes and/or minute centric fragments. The nucleolar chromosomes ofS. phureja were eliminated preferentially. The function of the remaining nucleolar organizer regions was not suppressed. Nuclear DNA content was correlated with the hypotetraploid chromosome numbers. PMID- 24232991 TI - Electroporation stimulates tranformation of freshly isolated cell suspension protoplasts ofSolanum dulcamara byAgrobacterium. AB - Freshly isolated cell suspension protoplasts ofSolanum dulcamara were mixed withAgrobacterium rhizogenes, allowed to settle for 2 h, exposed to electrical pulses and further incubated for 2h. Two pulses of 600 V cm(-1) for 2 msec separated by 15 sec produced transformed colonies at relative and absolute transformation frequencies which were 3-4 and 10 fold greater than those obtained by co-cultivation of 3 days old protoplast-derived cells with bacteria. Transformed colonies were not produced when freshly isolated protoplasts were mixed withAgrobacterium but not electroporated. Biochemical analysis confirmed the transgenic nature of plants regenerated from protoplast-derived tissues. PMID- 24232992 TI - Cyanide-initiated oxygen consumption in autoclaved culture medium containing sugars. AB - The consumption of oxygen initiated by KCN in an autoclaved sugar-containing rinse medium with protoplasts is described. The effect of autoclaving on several sugars was examined. Fructose solutions, followed in decreasing order by glucose, sucrose and sorbitol, were found to contain the largest amount of degraded products that could react with oxygen in the presence of KCN. Mannitol was found to be stable under the autoclaving conditions used in this investigation. KCN generally has an inhibitory effect on respiration, but in some plant tissues, respiration is stimulated by it. Under certain circumstances the degradation artefact described here may confuse interpretation of the results of respiration measurements. The use of autoclaved media containing sugars should be avoided in respiration studies that involve the application of KCN. PMID- 24232993 TI - Biosynthesis of phenolic compounds inVitis vinifera cell suspension cultures: Study on hydroxycinnamoyl CoA:ligase. AB - In cell suspensions cultures from grape berry pulp (Vitis vinifera cv. Gamay freaux)hydroxycinnamoyl CoA ligase (CoAL) displayed maximum activity (100 %) forp coumaric acid and then, in decreasing order, for ferulic acid (81.3 %) and caffeic acid (60.4 %). No activity was detected with sinapic and cinnamic acids. The changes in CoAL activity during the growth cycle of the culture displayed two peaks : the highest (6 h after subculturing) was linked with a strong increase in protein caused by dilution ; the second was weaker and occurred on the 7th day of culture.Grape cell suspension accumulated mainly peonidin (Pn) and cyanidin (Cy) glucosides (Pn 3-glucoside, Cy 3-glucoside, Pn 3-acetylglucoside, Pn 3 caffeylglucoside, Pn 3-p-coumarylglucoside, and Cy 3-p-coumarylglucoside). Maximum accumulation of anthocyanins was associated with the exponential growth phase of the culture and might be the result of the substantial increase in CoAL activity resulting from the effect of dilution. The second enzyme activity peak was probably oriented towards the acylation of anthocyanins since the percentage of acylated forms increased with time after subculturing. PMID- 24232994 TI - Transformed calli obtained by direct gene transfer into sunflower protoplasts. AB - Helianthus annuus protoplasts were transformed with the plasmid pCaMVNEO (Frommet al. 1986) conferring kanamycin resistance to plant. Transformed calli were selected with a frequency of 4 calli for 10(6) treated protoplasts. DNA was extracted from kanamycin resistant calli. Analysis of this DNA shows the presence of the NPTII gene. PMID- 24232995 TI - Stable ploidy levels in long-term callus cultures of loblolly pine. AB - Ploidy levels were calculated for callus cultures of loblolly pine (Pinus taeda L.), based on nuclear DNA content measured by Feulgen cytophotometry. The nuclear DNA content of initial stem explants showed a predominant 2C condition with less 3C and 4C, in ratios approximating those expected from diploid cells as they replicate DNA in the mitotic cell cycle. Cells with higher ploidy were produced during callus initiation, as indicated by a sharp reduction in the 2C population and a concomitant increase in higher DNA levels up to 8C. A gradual decrease in the higher ploidy levels occurred in subsequent subculture intervals, so that by 18 weeks the diploid nuclear DNA distribution was again observed, with complete elimination of DNA levels greater than 4C. Established callus cultures derived from stem or embryo explants and cultured on three different nutrient media for 48-76 weeks also showed the diploid nuclear DNA distribution with no indication of polyploid cells. PMID- 24232996 TI - Genetic control of embryo formation in anther culture of diploid potatoes. AB - A diploid potato clone AH 78/8015.37a with androgenetic ability was crossed with a root-knot nematode resistant diploid clone 381320.23 which did not have this ability.Among 19 F1 progenies tested a wide range of continuous variability was found for androgenetic capability. Four F1 clones with different level of embryo formation capability were backcrossed to 381320.23 to produce 4 F1BC1 families to further clarify the genetic control of androgenetic capability.From the wide range of continuous variability for androgenetic ability observed, it can be inferred that this character is controlled by more than one major gene.The occurrence of plants with androgenetic ability derived from parents both lacking this character, indicated that the androgenetic ability is controlled by recessive genes or results from complementation of various factors singly present in the parents. The present results demonstrated that the androgenetic ability could be transferred through sexual crosses, making it possible to successfully apply anther culture to other useful genetic material lacking this ability. PMID- 24232997 TI - Thermal stress evaluation of suspension cell cultures in winter wheat. AB - The objectives of this study were to compare thermotolerance in whole plants vs. suspension cell cultures of winter wheat, and to evaluate the synthesis of heat shock proteins in relation to genotypic differences in thermotolerance in suspension cells. Whole plant genetic differences in the development of heat tolerance were identified for three wheat genotypes (ND 7532, KS 75210 and TAM 101). Suspension cell cultures of these genotypes were used to evaluatein vitro response to heat stress. Viability tests by triphenyl tetrazolium chloride (TTC) and by fluorescein diacetate (FD) were utilized to determine the relationship of cellular response to heat stress (37 degrees C/24 h, 50 degrees C/1h). KS 75210 and ND 7532 are relatively heat susceptible. TAM 101 is heat tolerant. Both tests at the cellular level were similar to the whole plant response. Thus, cellular selection for enhancing heat tolerance seems feasible. Heat shock protein (HSP) synthesis of two genotypes, ND 7532 and TAM 101 were determined for suspension cultured cells. In suspension cultures, HSPs of molecular weight 16 and 17 kD were found to be synthesized at higher levels in the heat tolerant genotype (TAM 101) than the susceptible genotype (ND 7532), both at 34 degrees and 37 degrees C treatments for 2 hours and 5 hours. HSP 22 kD was synthesized more at 34 degrees C for TAM 101 than ND 7532, but not at 37 degrees C; whereas, HSP 33 kD was synthesized at 37 degrees C at similar abundance for both genotypes, but not at 34 degrees C.These results indicated that there is a differential expression of HSP genes in wheat suspension cells at different temperature stress durations and between heat tolerant and heat susceptible genotypes. It appears that the levels of synthesis of HSPs 16 and 17 kD are correlated with genotypic differences in thermal tolerance at the cellular level in two genotypes of wheat. PMID- 24232998 TI - Plant regeneration of wildGlycine species from suspension culture-derived protoplasts. AB - Protoplasts isolated from four-week old cell suspension cultures ofGlycine canescens F. J. Herm andG. clandestina Wendl. were cultured in 8P or modified 8P to a multicellular stage. Colonies of 0.5 to 1.0 mm diameter were transferred to solid media for callus growth and regeneration. Callus consisted of friable masses with compact green nodular areas. Organogenesis of both species occurred primarily from the green nodular areas. Shoot buds ofG. clandestina did not mature, but shoots ofG. canescens proliferated on MS medium, with B5 vitamins, 0.33 mgL(-1) each BA, KN, ZN, and 0.15 mgL(-1) NAA. Shoots failed to root after multiple subcultures on four different rooting media.In vitro grafting ofG. canescens scions ontoG. max root stocks allowed plants to be transferred to soil. An overall protoplast division efficiency of 48% was achieved with moderately efficient shoot regeneration inG. canescens. Division efficiencies forG. clandestina were lower (11%). Refinements of this protocol should result in high efficiencies of regeneration which would allowin vitro manipulations of these wild soybean relatives at the single cell level and would make the derivation of somatic hybrid plants possible within the genusGlycine. PMID- 24232999 TI - Organogenesis versus embryogenesis from long-term suspension cultures of cucumber (Cucumis sativus L.). AB - Suspension cultures were initiated from leaf explant-derived callus of cucumber,Cucumis sativus cv. Hokus, and maintained under two different conditions; (I) continuously in medium with 5 MUM 2,4-D + 5 MUM BA, and (II) alternately three cultures in medium containing 5 MUM NAA + 5 MUM BA and one culture in 5 MUM 2,4-D + 5 MUM BA. After plating on solid medium with 0.5 MUM KIN + 0.1 MUM IAA, suspension aggregates from long-term culture in medium with 2,4-D developed into callus, and subsequently formed somatic embryos. These embryos, however, hardly developed into plants. They showed growth arrest and several structural abnormalities. In contrast, organogenesis took place when suspension aggregates from NAA containing medium were plated on solid medium with 0.5 MUM KIN + 0.1 MUM IAA. Numerous adventitious buds were regenerated, which quite normally developed into plants. Sucrose at low concentration of 1% improved plant formation. On the average thirty complete plants were obtained from each ml of suspension. It is discussed why adventitious buds develop into plants so well, whereas somatic embryos are prone to growth arrest and abnormal development. PMID- 24233000 TI - Cell differentiation in protoplast cultures from embryogenic callus ofAbies alba L. AB - Protoplasts were isolated from embryogenic callus ofAbies alba L. which originated from immature seeds. The protoplasts were immobilized in alginate beads in order to follow the development of single protoplasts.Surrounding culture medium was modified from Kao and Michayluk (1975). After cell wall regeneration subsequent cell divisions lead to the formation of colonies showing an early differentiation of small meristematic cells and large vacuolated "suspensor-type" cells. PMID- 24233001 TI - Somatic embryogenesis and plant regeneration from cell suspension and tissue cultures of mature himalayan poplar (Populus ciliata). AB - Somatic embryogenesis and plantlet formation were obtained from callus and cell suspension cultures of 40-year- old Himalayan Poplar (Populus ciliata Wall ex Royle). Callus and cell suspensions were obtained by transfer of inoculum of semiorganized leaf cultures, which were maintained on Murashige and Skoog (MS) medium supplemented with benzylaminopurine (BAP), to MS with 2,4 dichlorophenoxyacetic acid (2,4-D). Reduction of 2,4-D concentration during subsequent subculture of cell suspensions resulted in the formation of embryoids. These embryoids developed further only after being transferred to agar-based MS medium supplemented with BAP and naphthalene acetic acid. Loss of embryogenic potential was observed in cell suspensions after 6 subcultures. However, callus cultures retained the embryogenic potential even after repeated subcultures for more than a year. Plantlets could be successfully hardened and grown in natural outdoor conditions. PMID- 24233002 TI - Biotransformation of (-)-codeinone to (-)-codeine byPapaver somniferum cells immobilized in reticulate polyurethane foam. AB - Papaver somniferum cells immobilized in reticulate-polyurethane foam biotransformed (-)-codeinone to (-)-codeine. A biotransformation ratio of 79% was found in immobilized cells whereas a ratio of 57% was found in suspended cells. Of the total amount of codeine formed only 12.2% was detected inside the cells, most of the product (87.3%) being released into the medium. When immobilized cells were cultivated in the absence of nitrate, only 40% of the cells remained alive and the biotransformation of codeinone was strongly reduced. When orthophosphate was omitted from the growth medium a bioconversion ratio of 86% was achieved. PMID- 24233003 TI - Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy. AB - PURPOSE: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ((90)Y) and a medium-energy beta/gamma emitter ([(177)Lu) in patients with metastatic NET refractory to conventional therapy. METHODS: A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [[(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [[(177)Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. RESULTS: Administration of tandem [(90)Y]DOTA-TATE and [[(177)Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment. CONCLUSION: The results of our study indicates that combined [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. PMID- 24233004 TI - Imaging of amyloid deposition in human brain using positron emission tomography and [18F]FACT: comparison with [11C]PIB. AB - PURPOSE: The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The (18)F labeled amyloid tracer, [(18)F]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5 yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [(11)C]Pittsburgh compound B (PIB) and [(18)F]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared. METHODS: Two PET scans, one of each with [(11)C]PIB and [(18)F]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation. RESULTS: No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [(18)F]FACT studies without partial volume correction, while significant differences were observed in [(11)C]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [(18)F]FACT studies as well as [(11)C]PIB. Relatively lower uptakes of [(11)C]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [(18)F]FACT. Relatively higher uptake of [(11)C]PIB in distribution was observed in the frontal and parietal cortices. CONCLUSION: Since [(18)F]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [(11)C]PIB and [(18)F]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the autoradiographic and histochemical assays of postmortem AD brain sections. PMID- 24233005 TI - Preoperative PET/CT FDG standardized uptake value of pelvic lymph nodes as a significant prognostic factor in patients with uterine cervical cancer. AB - PURPOSE: Using integrated PET/CT, we evaluated the prognostic relevance in uterine cervical cancer of preoperative pelvic lymph node (LN) [(18)F]FDG uptake. METHODS: Patients with FIGO stage IB to IIA uterine cervical cancer were imaged with FDG PET/CT before radical surgery. We used Cox proportional hazards regression to examine the relationship between recurrence and the FDG maximum standardized uptake value (SUV(max)) in the pelvic LN (SUVLN) on PET/CT. RESULTS: Clinical data, treatment modalities, and results in 130 eligible patients were reviewed. The median postsurgical follow-up was 34 months (range 6 to 109 months). Receiver operating characteristic analysis identified SUVLN 2.36 as the most significant cut-off value for predicting recurrence. SUV(LN) was correlated with SUV(tumour) (P = 0.002), primary tumour size (P = 0.004), and parametrial invasion (P = 0.013). Univariate analyses showed significant associations between recurrence and SUV(LN) (P = 0.001), SUV(tumour) (P = 0.007), pelvic LN metastasis (P = 0.002), parametrial invasion (P < 0.001), primary tumour size (P = 0.007), suspected LN metastasis on MRI (P = 0.024), and FIGO stage (P = 0.026). Multivariate analysis identified SUV(LN) (P = 0.013, hazard ratio, HR, 4.447, 95 % confidence interval, CI, 1.379 - 14.343) and parametrial invasion (P = 0.013, HR 6.728, 95 % CI 1.497 - 30.235) as independent risk factors for recurrence. Patients with SUV(LN) >= 2.36 and SUV(LN) <2.36 differed significantly in terms of recurrence (HR 15.20, P < 0.001). CONCLUSION: Preoperative pelvic LN FDG uptake showed a strong significant association with uterine cervical cancer recurrence. PMID- 24233006 TI - The zygote cell wall of Chlamydomonas reinhardii: a structural, chemical and immunological approach. AB - The zygote cell wall of Chlamydomonas reinhardii has been studied using structural, chemical and immunological methods. Monoclonal antibodies and polyclonal antisera that were originally raised to the major hydroxyproline-rich glycoproteins of the vegetative cell wall were used to probe the zygote wall for common antigenic components. These antibodies cross-reacted strongly and specifically with components of the zygote cell wall, and were used to show the origin, route of transport, and the location of these antigens within the zygote cell wall. The zygote cell wall contained about 10% protein, with hydroxyproline accounting for 22.5 mol % of the total amino acids present. Glucose was the most abundant sugar residue, and accounted for 56% of the total sugar present. Gas liquid chromatography-mass spectrometry showed the presence of a (1-3)beta-D glucan as the major structural polysaccharide within the zygote cell wall. The (1 3)beta-D-glucan was detected and localised within the zygote cell wall by immunogold labelling of thin sections. Using an antiserum directed against (1 3)beta-D-linked glucose units, this polysaccharide was found to be consistently present within the non-staining layer of both young and mature zygote cell walls. (1-3)beta-D-Glucan was also detected in other wall layer using higher concentrations of antiserum. No intracellular labelling was found, indicating that the plasmamembrane is the site for the synthesis of this polysaccharide within the Chlamydomonas zygote. PMID- 24233007 TI - Quantitative cytology of the sperm cells of Brassica campestris and B. oleracea. AB - Pollen grains of Brassica campestris L. var. acephala DC and B. oleracea L. were serially sectioned and examined using transmission electron microscopy to determine the three-dimensional organization of sperm cells within the microgametophyte and the quantity of membrane-bound organelles occurring within each cell. Sperm cells occur in pairs within each pollen grain, but are dimorphic, differing in size, morphology and mitochondrial content. The larger of the two sperm cells (Svn) is distinguished by the presence of a blunt evagination, which in B. oleracea wraps around and lies within shallow furrows on the vegetative nucleus and in B. campestris can penetrate through internal enclaves of the vegetative nucleus. This sperm cell contains more mitochondria in both species than the second sperm cell (Sua). This latter cell is linked to the first by a common cell junction with the S vn, but is not associated with the vegetative nucleus and lacks a cellular evagination. Such differences are indicative of a system of cytoplasmic heterospermy in which sperm cells possess significantly different quantities of mitochondria. PMID- 24233008 TI - Light-induced changes in the amounts of the 36000-Mr polypeptide of NADPH protochlorophyllide oxidoreductase and its mRNA in barley plants grown under a diurnal light/dark cycle. AB - Seedlings of barley were grown either in continuous darkness or under a diurnal 12 h light/12 h dark cycle and the effects on NADPH-protochlorophyllide oxidoreductase were followed at two different levels. Firstly, the relative content of the mRNA encoding the NADPH-protochlorophyllide oxidoreductase was measured by dot-blot hybridization. Secondly, changes in the enzyme polypeptide were monitored either by the method of immunoblotting or by immunogold labelling of ultrathin sections of Lowicryl-embedded leaf tissue. Our results demonstrate that drastic diurnal changes in the level of mRNA sequences and the enzyme protein are unlikely to occur in plants which have been grown under natural light/dark conditions. In the dark, protein and mRNA accumulation occurs at an early developmental stage. These results are difficult to reconcile with the suggestion that the massive accumulation of mRNA and enzyme protein in dark-grown seedlings is primarily the consequence of an artificially extended darkperiod. In addition to the plastid-specific NADPH-protochlorophyllide oxidoreductase a closely related polypeptide has been detected outside the plastid in the surrounding cytoplasm (Dehseh et al. 1986b, Planta 169, 172-183). During the diurnal light/dark treatment of seedlings the concentrations of the two protein populations did not show any variation indicative of an exchange between the two protein populations across the plastid envelope. PMID- 24233009 TI - Immunocytochemical localisation of phloem lectin from Cucurbita maxima using peroxidase and colloidal-gold labels. AB - Antibodies were raised against lectin purified from the sieve-tube exudate of Cucurbita maxima. Immunocytochemistry, using peroxidase-labelled antibodies and Protein A-colloidal gold, was employed to determine the location of the lectin within the tissues and cells of C. maxima and other cucurbit species. The anti lectin antibodies bound to P-protein aggregates in sieve elements and companion cells, predominantly in the extrafascicular phloem of C. maxima. This may reflect the low rate of translocation in these cells. Under the electron microscope, the lectin was shown to be a component of P-protein filaments and was also found in association with the sieve-tube reticulum which lines the plasmalemma. The anti lectin antibodies reacted with sieve-tube proteins from other species of the genus Cucurbita but showed only limited reaction with other genera. We suggest that the lectin serves to anchor P-protein filaments and associated proteins to the parietal layer of sieve elements. PMID- 24233010 TI - High-temperature damage and acclimation of the photosynthetic apparatus : I. Temperature sensitivity of some photosynthetic parameters of chloroplasts isolated from acclimated and non-acclimated bean leaves. AB - The thermosensitivity of delayed fluorescence, the relative values of variable chlorophyll fluorescence and the degree of quenching of 9-aminoacridine fluorescene were studied in the chloroplasts from heat-acclimated and non acclimated (treated 6 h at 52,5 degrees C) young bean plants. The temperature sensitivity of each parameter studied was defined by that temperature at which chloroplast activity decreased by 50% (T50) of its maximum value. There was appreciable increase in the thermostability of membrane energization in chloroplasts isolated from acclimated and non-acclimated plants compared with the controls. The photosynthetic parameters differed according to the suspending medium and the preacclimation treatment. When chloroplast were suspended in phosphate buffer with the addition of stabilizing compounds (2 M sucrose or 0.5% human serum albumin) the thermostability of the thylakoid membranes increased, as was evident by the increases in T50 of about 8-10 degrees C (sucrose) and 2-5 degrees C (human serum albumin) for all the parameters investigated. Photoinduced quenching of 9-aminoacridine fluorescence decreased to some extent in the presence of protective compounds, but in chloroplasts from acclimated plants the T50 was practically equal to that for their long-lived luminescence under the same conditions. At the thylakoid membrane level, acclimation was clearly manifested as an increased thermostability of photoinduced proton gradient formation. PMID- 24233011 TI - High-temperature damage and acclimation of the photosynthetic apparatus : II. Effect of mono- and divalent cations and pH on the temperature sensitivity of some functional characteristics of chloroplasts isolated from heat-acclimated and non-acclimated bean plants. AB - The influence of mono- (K(+)) and divalent (Mg(2+)) cations and protons (pH) on the temperature sensitivity of thylakoid membranes was investigated in three groups of young bean plants (control, heat-acclimated and non-acclimated). Thylakoid-membrane function was monitored by second and millisecond delayed fluorescence and 9-aminoacridine fluorescence quenching. It was established that metal ions at investigated concentrations decreased the thermostability of the photosynthetic parameters - an increase of MgSO4 concentration from 0.1 to 20 mM decreased the temperature of their half-inactivation (T50) by 13 degrees C. At the same time the pH dependence of the thermal stability of these parameters showed a maximum at pH 5.5-6.5. The half-inactivation temperatures of those photosynthetic parameters connected with the ability of the thylakoid membrane to form light-induced proton gradients increased by 6-7 degrees C in the heat acclimated plants compared with the control. It was assumed that the temperature inactivation of photosynthetic electron transfer and the energization of the thylakoid membrane was determined both by the thermoinduced dissociation of the light-harvesting chlorophyll a/b protein complex from PSII, leading to destruction of the excitation energy transfer to the reaction centres, and by the thermal denaturation of the membrane-protein components. The rate of these processes was probably controlled by the size of the negative surface charge and the viscosity of the thylakoid membrane. PMID- 24233012 TI - Photon yield of O2 evolution and chlorophyll fluorescence characteristics at 77 K among vascular plants of diverse origins. AB - Photon yields of oxygen evolution at saturating CO2 were determined for 44 species of vascular plants, representing widely diverse taxa, habitats, life forms and growth conditions. The photonyield values on the basis of absorbed light (phi (a)) were remarkably constant among plants possessing the same pathway of photosynthetic CO2 fixation, provided the plants had not been subjected to environmental stress. The mean phi (a) value +/-SE for 37 C3 species was 0.106+/ 0.001 O2.photon(-1). The five C4 species exhibited lower photon yields and greater variation than the C3 species (phi (a)=0.0692+/-0.004). The phi (a) values for the two Crassulaceanacid-metabolism species were similar to those of C3 species. Leaf chlorophyll content had little influence on phi (a) over the range found in normal, healthy leaves. Chlorophyll fluorescence characteristics at 77 K were determined for the same leaves as used for the photon-yield measurements. Considerable variation in fluorescence emission both at 692 nm and at 734 nm, was found 1) among the different species; 2) between the upper and lower surfaces of the same leaves; and 3) between sun and shade leaves of the same species. By contrast, the ratio of variable to maximum fluorescence emission at 692 nm (Fv/FM, 692) remained remarkably constant (The mean value for the C3 species was 0.832+/-0.004). High-light treatments of shade leaves resulted in a reduction in both phi (a) and the Fv/FM, 692 ratio. The extent of the reductions increased with time of exposure to bright light. A linear relationship was obtained when phi (a) was plotted against Fv/FM, 692. The results show that determinations of the photon yield of O2 evolution and the Fv/FM, 692 ratio can serve as excellent quantitative measures of photoinhibition of overall photosynthetic energy-conversion system and of photochemistry of photosystem II, respectively. This is especially valuable in field work where it is often impossible to obtain appropriate controls. PMID- 24233013 TI - Comparison of the effects of exogenous native phytochrome and in-vivo irradiation on in-vitro transcription in isolated nuclei from barley (Hordeum vulgare). AB - In barley seedlings the transcription of genes coding for the light-harvesting chlorophyll a/b protein (LHCP) is stimulated and the transcription of genes coding for the NADPH-protochlorophyllide oxidoreductase (reductase) is repressed by light working via the phytochrome system. This phytochrome-mediated control of gene expression has been studied by monitoring in-vitro transcription in isolated nuclei. Two different experimental approaches have been used to elucidate the function of phytochrome (Pfr) during the transduction of the light signal. Concentrations of phytochrome were varied experimentally either by illuminating intact plants or macerated plant material prior to the isolation of nuclei or by adding purified phytochrome (Pfr) in its native 124-kDa form to the isolated nuclei. Our results indicate that there are at least two different steps involved in the phytochrome control of specific gene expression. (i) There is a rapid and transient change in the transcription rate which is saturated by very low levels of Pfr. (ii) There is a change in the duration and the maximum range of the transient change; this step requires relatively high Pfr concentrations and thus reacts very sensitively and rapidly to changes in Pfr levels as induced by secondary irradiations. This second step, but not the first one, could be triggered by the addition of purified oat phytochrome to a reconstituted nuclear system. This effect of purified phytochrome could only be shown if nuclei isolated from red-light (R)-irradiated seedlings were used. It was thus possible to simulate the effect of an in-vivo-applied second R pulse by the addition of Pfr to nuclei isolated from R-preirradiated plants. PMID- 24233014 TI - Resolution of two molecular forms of sucrose-phosphate synthase from maize, soybean and spinach leaves. AB - Two forms of sucrose-phosphate synthase (EC 2.4.1.14) were resolved from leaves of three species, maize (Zea mays L. cv. Pioneer 3184), soybean (Glycine max (L.) Merr., cv. Ransom) and spinach (Spinacia oleracea L. cv. Resistoflay) by hydroxyapatite Ultrogel chromatography, using a 75-mM (designated peak 1) and 250 mM (peak 2) K-phosphate discontinuous-gradient elution. Rechromatography of the two forms showed that they were not readily interconvertible. The distribution of activity between the two forms differed among species and changed during purification of the enzyme. Recovery of peak-1 activity was specifically lowered when maize leaf extracts were prepared in the absence of magnesium, indicating that the two forms may differ in stability. In addition, the forms of the enzyme from maize differed in the extent of glucose-6-phosphate activation. These results provide evidence for the existence of multiple forms of sucrose-phosphate synthase in leaves of different species and that the forms differ in regulatory properties. PMID- 24233015 TI - Chloroplast photooxidation affects the accumulation of cytosolic mRNAs encoding chloroplast proteins in maize. AB - Maize (Zea mays L.) seedlings were grown in the presence or absence of an herbicide, norflurazon (4-chloro-5-(methylamino)-2-(alpha,alpha,alpha-trifluoro-m tolyl)-pyridazinone), which prevents the accumulation of colored carotenoids. In the absence of carotenoids, plants grown in high light incur extensive photooxidative damage to their plastids, but relatively little damage elsewhere. Growth in very low light minimizes chlorophyll photooxidation and allows chloroplast development to proceed. We have previously reported that mRNA encoding light-harvesting chlorophyll a/b protein (LHCP) fails to accumulate in high-light-grown carotenoid-deficient seedlings, but accumulates normally in carotenoid-deficient seedlings grown in low light. Here we extend these results by examining the levels of translatable mRNAs encoding seven additional nuclear encoded chloroplast proteins. When norflurazon-treated seedlings were grown in low light for 8 d and then transferred to high light for 24 h, three cytosolic mRNAs (plastocyanin, Rieske Fe-S protein, and the 33-kdalton (kDa) subunit of the photosystem II O2-evolving complex) decreased to less than 1% the amount found in untreated seedlings. Two other mRNAs (NADP malic enzyme, EC 1.1.1.40, and the 23 kDa subunit of the photosystem II O2-evolving complex) decreased significantly but not to levels as low as the first three. Levels of translatable mRNA for two other chloroplast proteins (pyruvate orthophosphate dikinase, EC 2.7.9.1, and ferredoxin NADP oxidoreductase, EC 1.18.1.2) were not reduced in nonflurazon treated seedlings after 24 h in high light, but did not show the normal light induced increase found in untreated plants. Photooxidative damage in the chloroplast thus affects the accumulation of a number of cytosolic mRNAs encoding proteins destined for the chloroplast. PMID- 24233016 TI - D-Mannitol dehydrogenase and D-mannitol-1-phosphate dehydrogenase in Platymonas subcordiformis: some characteristics and their role in osmotic adaptation. AB - D-Mannitol-1-phosphate dehydrogenase (EC 1.1.1.17) and D-mannitol dehydrogenase (EC 1.1.1.67) were estimated in a cell-free extract of the unicellular alga Platymonas subcordiformis Hazen (Prasinophyceae), D-Mannitol dehydrogenase had two activity maxima at pH 7.0 and 9.5, and a substrate specifity for D-fructose and NADH or for D-mannitol and NAD(+). The K m values were 43 mM for D-fructose and 10 mM for D-mannitol. D-Mannitol-1-phosphate dehydrogenase had a maximum activity at pH 7.5 and was specific for D-fructose 6-phosphate and NADH. The K m value for D-fructose 6-phosphate was 5.5 mM. The reverse reaction with D-mannitol 1-phosphate as substrate could not be detected in the extract. After the addition of NaCl (up to 800 mM) to the enzyme assay, the activity of D-mannitol dehydrogenase was strongly inhibited while the activity of D-mannitol-1-phosphate dehydrogenase was enhanced. Under salt stress the K m values of the D-mannitol dehydrogenase were shifted to higher values. The K m value for D-fructose 6 phosphate as substrate for D-mannitol-1-phosphate dehydrogenase remained constant. Hence, it is concluded that in Platymonas the D-mannitol pool is derectly regulated via alternative pathways with different activities dependent on the osmotic pressure. PMID- 24233017 TI - Regulated expression of an alcohol dehydrogenase 1 chimeric gene introduced into maize protoplasts. AB - Transient-expression analysis has shown anaerobic regulation of the alcohol dehydrogenase (Adh1) promoter in a chimeric construct. Chimeric plasmids containing the promoter for the Adh1 gene of maize (Zea mays L.) linked to the coding sequence of the chloramphenicol acetyl transferase (cat) gene were introduced into maize protoplasts using electroporation. Both the introduced Adh1 promoter and the endogenous Adh1 gene promoter are regulated at the RNA level, the O2-tension optimum for induction is the same for both, and both promoters initiate transcription from the same site. The demonstration of regulation of a plant gene promoter in a transient expression system will allow the identification of cis acting sequences responsible for regulation. PMID- 24233018 TI - Proteases of Melilotus alba mesophyll protoplasts : II. General properties and effectiveness in degradation of cytosolic and vacuolar enzymes. AB - Proteases from mesophyll protoplasts of Melilotus alba were identified by standard proteolytic assays and separated using different chromatographic techniques. Their characterization also included their subcellular location. Besides the evidence for the multiplicity of the proteolytic enzymes, two protease sets were distinguished endopeptidases, which are exclusively vacuolar, and aminopeptidases, which are widely distributed throughout the cell. Cytosol located enzymes were tested as substrates of the two sets of proteases, by studying comparatively the time-course changes of enzyme activities during incubation in total protoplast extracts, or in cytosol fractions devoid of vacuolar proteases. The degradation of phosphoenolpyruvate-carboxylase protein, a typical cytosolic enzyme, in the presence of purified amino-and endopeptidases, was also estimated by immunoprecipitation studies. Only the vacuolar endopeptidases are effective in the degradation of cytosolic enzymes. Hydrolytic enzyme activities mostly of vacuolar origin were very stable during incubation in total protoplast extracts. These proteins therefore appear to be particularly resistant to proteolytic attack. The results indicate that, in plants, the effective proteolytic system acting on cytosolic enzymes seems to be vacuole located, and that the selectivity in protein degradation may be imposed by the susceptibility of the protein being degraded and by its transfer into the vacuoles. PMID- 24233019 TI - Short-term studies of NO 3 (-) uptake in Pisum using (13)NO 3 (-). AB - Influx, efflux and net uptake of NO 3 (-) was studied in Pisum sativum L. cv. Marma in short-term experiments where (13)NO 3 (-) was used to trace influx. The influx rate in N-limited plants was similar both during net uptake at external concentrations of around 50 MUM, and at low external NO 3 (-) concentrations (4-6 MUM) when net uptake was practically zero. Efflux could be inferred from discrepancies between influx and net uptake but was never very high in the N limited plants during net uptake. Close to the threshold concentration for not NO 3 (-) uptake, efflux was high and equalled influx. Thus, the threshold concentration can be regarded as a NO 3 (-) compensation point. The inclusion of NH 4 (+) in the outer medium decreased influx by about 40% but did not significantly affect efflux. The roles of NO 3 (-) fluxes and nitrate-reductase activity in regulating/limiting NO 3 (-) utilization are discussed. PMID- 24233020 TI - Biochemical reactions of different tissues of potato (Solanum tuberosum) to zoospores or elicitors from Phytophthora infestans : Accumulation of sesquiterpenoid phytoalexins. AB - The time courses of sesquiterpenoid phytoalexin accumulation were examined in compatible and incompatible interactions of leaves and tubers from five different R genotypes of potato (Solanum tuberosum) with corresponding pathotypes of Phytophthora infestans, as well as in non-host interactions of all five potato cultivars with Phytophthora megasperma f. sp. glycinea and in elicitor-treated tubers from five, and cell suspension cultures from two, of the cultivars. In tubers, rishitin and several structurally related sesquiterpene derivatives accumulated rapidly in non-host incompatible interactions, less rapidly in host incompatible interactions, and more slowly in compatible interactions. Treatment of tubers or cell cultures with fungal culture filtrate or arachidonic acid elicited in most cases a transient accumulation of the sesquiterpenoid phytoalexins. None of these compounds was detectable under any of the applied conditions either in infected or in elicitortreated leaves. Sesquiterpenoid phytoalexins might therefore be helpful, but appear not to be essential, in disease resistance of potato. PMID- 24233021 TI - Changes in legumin messenger RNAs throughout seed development in Pisum sativum L. AB - The patterns of accumulation of three classes of legumin mRNA from Pisum sativum have been followed through seed development by cell-free translation and hybridization to complementary DNAs. Maximum amounts of mRNA were found at 19 days after flowering (DAF) for two classes and at 24 DAF for the third class. The proportions of the three classes varied through development: the RNA species which was 40% of the total legumin mRNA at 14 DAF represented 15-20% of the total at 25-27 DAF, whereas a second mRNA species represented approx. 30% and 70% at the same stages, respectively. Based on these results, some deductions about the possible contribution of individual genes within classes are made. PMID- 24233022 TI - Competitive performance, training load and physiological responses during tapering in young swimmers. AB - The study examined the changes of training load and physiological parameters in relation to competitive performance during a period leading to a national championship. The training content of twelve swimmers (age: 14.2+/-1.3 yrs) was recorded four weeks before the national championship (two weeks of normal training and two weeks of the taper). The training load was calculated: i) by the swimmer's session-RPE score (RPE-Load), ii) by the training intensity levels adjusted after a 7*200-m progressively increasing intensity test (LA-Load). Swimmers completed a 400-m submaximal intensity test, a 15 s tethered swimming and hand-grip strength measurements 34-35 (baseline: Test 1), 20-21 (before taper: Test 2) and 6-7 (Test 3) days before the national championship. Performance during the national championship was not significantly changed compared to season best (0.1+/-1.6%; 95% confidence limits: -0.9, 1.1%; Effect Size: 0.02, p=0.72) and compared to performance before the start of the two-week taper period (0.9+/-1.7%; 95% confidence limits: 0.3, 2.1%; Effect size: 0.12, p=0.09). No significant changes were observed in all measured physiological and performance related variables between Test 1, Test 2, and Test 3. Changes in RPE Load (week-4 vs. week-1) were correlated with changes in performance (r=0.63, p=0.03) and the RPE-Load was correlated with the LA-Load (r=0.80, p=0.01). The estimation of the session-RPE training load may be helpful for taper planning of young swimmers. Increasing the difference between the normal and last week of taper training load may facilitate performance improvements. PMID- 24233023 TI - Metformin enhances glucagon-like peptide 1 via cooperation between insulin and Wnt signaling. AB - One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer. However, this remains completely unknown. In this study, we have investigated the mechanisms of the action of metformin on cross talk between insulin and Wnt signaling. GLP1 enhancement by meformin was determined in human NCI-H716 intestinal L-cells and hyperglycemic db/db mice treated with metformin (0.25 and 0.5 mM and/or 12.5 mg/kg body weight) for 24 h and 2 months. Metformin increased GLP1 secretion in L-cells and db/db mice. Metformin stimulated the nuclear translocation of beta-catenin and TOPflash reporter activity, and gene depletion of beta-catenin or enhancement of mutation of transcription factor 7 like 2 binding site offset GLP1. In addition, insulin receptor substrate 2 gene depletion blocked metformin-enhanced beta-catenin translocation. These effects were preceded by an increase in glucose utilization and calcium influx, the activation of calcium-dependent protein kinase, and, in turn, the activation of insulin signaling, and the inhibition of glycogen synthase kinase 3beta, a potent inhibitor of beta-catenin. Furthermore, high blood glucose levels were controlled via GLP1 receptor-dependent insulinotropic pathways in db/db mice, which were evidenced by the increase in GLP1 and insulin levels at 30 min after oral glucose loading and pancreatic insulinotropic gene expression. Our findings indicate that the cooperation between Wnt and its upstream insulin signaling pathways might be a novel and important mechanism underlying the effects of metformin on GLP1 production. PMID- 24233025 TI - Evaluation of stiffness changes in a high-rise building by measurements of lateral displacements using GPS technology. AB - The outrigger truss system is one of the most frequently used lateral load resisting structural systems. However, little research has been reported on the effect of installation of outrigger trusses on improvement of lateral stiffness of a high-rise building through full-scale measurements. In this paper, stiffness changes of a high-rise building due to installation of outrigger trusses have been evaluated by measuring lateral displacements using a global positioning system (GPS). To confirm the error range of the GPS measurement system used in the full-scale measurement tests, the GPS displacement monitoring system is investigated through a free vibration test of the experimental model. Then, for the evaluation of lateral stiffness of a high-rise building under construction, the GPS displacement monitoring system is applied to measurements of lateral displacements of a 66-story high-rise building before and after installation of outrigger truss. The stiffness improvement of the building before and after the installation is confirmed through the changes of the natural frequencies and the ratios of the base shear forces to the roof displacements. PMID- 24233024 TI - Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. AB - Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-kappaB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-kappaB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-kappaB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-kappaB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. PMID- 24233026 TI - Development of on-line monitoring systems for high temperature components in power plants. AB - To accurately detect deformation and extend the component life beyond the original design limits, structural safety monitoring techniques have attracted considerable attention in the power and process industries for decades. In this paper an on-line monitoring system for high temperature pipes in a power plant is developed. The extension-based sensing devices are amounted on straight pipes, T Joints and elbows of a main steam pipeline. During on-site monitoring for more than two years, most of the sensors worked reliably and steadily. However, the direct strain gauge could not work for long periods because of the high temperature environment. Moreover, it is found that the installation and connection of the extensometers can have a significant influence on the measurement results. The on-line monitoring system has a good alarming function which is demonstrated by detecting a steam leakage of the header. PMID- 24233027 TI - Kalman/Map filtering-aided fast normalized cross correlation-based Wi-Fi fingerprinting location sensing. AB - A Kalman/map filtering (KMF)-aided fast normalized cross correlation (FNCC)-based Wi-Fi fingerprinting location sensing system is proposed in this paper. Compared with conventional neighbor selection algorithms that calculate localization results with received signal strength (RSS) mean samples, the proposed FNCC algorithm makes use of all the on-line RSS samples and reference point RSS variations to achieve higher fingerprinting accuracy. The FNCC computes efficiently while maintaining the same accuracy as the basic normalized cross correlation. Additionally, a KMF is also proposed to process fingerprinting localization results. It employs a new map matching algorithm to nonlinearize the linear location prediction process of Kalman filtering (KF) that takes advantage of spatial proximities of consecutive localization results. With a calibration model integrated into an indoor map, the map matching algorithm corrects unreasonable prediction locations of the KF according to the building interior structure. Thus, more accurate prediction locations are obtained. Using these locations, the KMF considerably improves fingerprinting algorithm performance. Experimental results demonstrate that the FNCC algorithm with reduced computational complexity outperforms other neighbor selection algorithms and the KMF effectively improves location sensing accuracy by using indoor map information and spatial proximities of consecutive localization results. PMID- 24233028 TI - Discrimination method of the volatiles from fresh mushrooms by an electronic nose using a trapping system and statistical standardization to reduce sensor value variation. AB - Electronic noses have the benefit of obtaining smell information in a simple and objective manner, therefore, many applications have been developed for broad analysis areas such as food, drinks, cosmetics, medicine, and agriculture. However, measurement values from electronic noses have a tendency to vary under humidity or alcohol exposure conditions, since several types of sensors in the devices are affected by such variables. Consequently, we show three techniques for reducing the variation of sensor values: (1) using a trapping system to reduce the infering components; (2) performing statistical standardization (calculation of z-score); and (3) selecting suitable sensors. With these techniques, we discriminated the volatiles of four types of fresh mushrooms: golden needle (Flammulina velutipes), white mushroom (Agaricus bisporus), shiitake (Lentinus edodes), and eryngii (Pleurotus eryngii) among six fresh mushrooms (hen of the woods (Grifola frondosa), shimeji (Hypsizygus marmoreus) plus the above mushrooms). Additionally, we succeeded in discrimination of white mushroom, only comparing with artificial mushroom flavors, such as champignon flavor and truffle flavor. In conclusion, our techniques will expand the options to reduce variations in sensor values. PMID- 24233029 TI - More of the same epidemiology? PMID- 24233030 TI - Genetics of complex diseases: knowing gene polymorphisms do matter. PMID- 24233031 TI - [Food and nutrition education in school: a literature review]. AB - Food and nutrition education is viewed as a key strategy for promoting healthy eating habits, and the school is an appropriate space for developing these activities. The objective of this study was to describe and analyze the scientific literature on intervention studies on food and nutrition education in Brazilian schools. A literature review was conducted, selecting articles published from 2000 to 2011. Despite the topic's current importance, there were few articles, and most were published after 2009. The main results showed improvement in the children's nutritional knowledge and food choices. However, most studies that performed anthropometric measurements failed to show changes in nutritional status. In addition, the studies chose designs based on epidemiological intervention studies, indicating the need for interventions based on innovative health education methodologies and research models that are consistent with the study's objects. PMID- 24233032 TI - Assessment of the contents related to screening on Portuguese language websites providing information on breast and prostate cancer. AB - The objective of this study was to assess the quality of the contents related to screening in a sample of websites providing information on breast and prostate cancer in the Portuguese language. The first 200 results of each cancer-specific Google search were considered. The accuracy of the screening contents was defined in accordance with the state of the art, and its readability was assessed. Most websites mentioned mammography as a method for breast cancer screening (80%), although only 28% referred to it as the only recommended method. Almost all websites mentioned PSA evaluation as a possible screening test, but correct information regarding its effectiveness was given in less than 10%. For both breast and prostate cancer screening contents, the potential for overdiagnosis and false positive results was seldom addressed, and the median readability index was approximately 70. There is ample margin for improving the quality of websites providing information on breast and prostate cancer in Portuguese. PMID- 24233033 TI - [Low back pain and associated factors in children and adolescents in a private school in Southern Brazil]. AB - Studies have shown that children and adolescents with low back pain are also similarly affected when they reach adulthood, thus highlighting the importance of investigating causes of low back pain in school-age children. The study examined low back pain and associated factors in 770 schoolchildren 7 to 17 years of age in a private school in Porto Alegre, Rio Grande do Sul State, Brazil. Low back pain was defined as pain or discomfort in the lumbar region in the previous month, assessed by a questionnaire. Low back pain was found in 31.6% of the subjects and was more prevalent in girls (41.9%) than boys (21.4%). Factors associated with lumbar pain were female gender, age 9 to 17 years, hyperactivity (borderline and abnormal categories), and emotional symptoms (abnormal category). Mapping the occurrence of low back pain and associated factors is important for identifying children and adolescents at risk and for developing effective programs for primary prevention. PMID- 24233034 TI - [Acupuncture patients' experience in the Brazilian Unified National Health System in different healthcare settings and social (de)medicalization]. AB - The virtues attributed to complementary therapies such as holistic and patient centered approaches and stimulus for self-healing have been increasingly valued and could theoretically attenuate the current prevailing excessive social medicalization. Among such therapies, acupuncture has been highlighted due to its progressive institutionalization and acceptance. The objective of the current study was to analyze the experience of acupuncture patients in the Brazilian Unified National Health System and its relationship to their care, in light of social medicalization in terms of the constitutive aspects, representations, and users' explanatory models. Thirty patients were interviewed, selected from primary and secondary care services in Florianopolis, Santa Catarina State, Brazil. Important therapeutic results were observed in the principal complaints, sleep, disposition, emotional status, and decreased use of medication. Users' explanatory models and self-care were modified very little, or not at all, by acupuncture treatment. However, the study showed expanded and less iatrogenic care, especially in the primary care setting, in which there was little supply of other associated practices from Chinese medicine. PMID- 24233035 TI - Factors associated with time free of oral candidiasis in children living with HIV/AIDS, Sao Paulo, Brazil. AB - In clinical practice, recurrence of thrush is common in children living with HIV/AIDS. The aim of this study was to determine the factors associated with time spent free of oral candidiasis using survival analysis for recurrent events. A retrospective cohort study was carried out with 287 children treated between 1985 and 2009 at a reference center in the city of Sao Paulo, Brazil. The Prentice, Williams and Peterson model for recurrent events was used for the investigation of factors associated with the time free of oral candidiasis. The following factors were associated with the time patients were free of oral candidiasis: moderate immunodepression (HR = 2.5; p = 0.005), severe immunodepression (HR = 3.5; p < 0.001), anemia (HR = 3.3; p < 0.001), malnutrition (HR = 2.6; p = 0.004), hospitalization (HR = 2.2; p < 0.001), monotherapy (HR = 0.5; p = 0.006), dual therapy (HR = 0.3; p < 0.001) and triple therapy/highly active antiretroviral therapy (HR = 0.1; p < 0.001). The method analyzed in the present study proved useful for the investigation of recurrent events in patients living with HIV/AIDS. PMID- 24233036 TI - Aggressors and resilient youths in Medellin, Colombia: the need for a paradigm shift in order to overcome violence. AB - The objective of this study was to estimate the ratio of resilient youth and compare this to youth with aggressive behavior, and to youth who also exhibit sexually risky behavior and drug use. A cross-section study of a representative sample of people between aged between 12 and 60 who are residents of Medellin, Colombia, and its metropolitan area (N = 4,654) was employed using probabilistic multi-stage sampling. Youth between 14 and 26 years old were selected for the present analysis (n = 1,780). The proportion of resilient youth is 22.9%, of aggressors is 11.3%, and that of youth with other risky conduct is 65.8%. The high ratio of resilient youth calls for a reorientation of public policy toward prevention and control of violence, prioritizing the promotion of resilient behavior instead of continuing with tertiary prevention actions. PMID- 24233037 TI - Prevalence of physical inactivity and associated factors among adolescents from public schools in Uruguaiana, Rio Grande do Sul State, Brazil. AB - This study aimed to identify the prevalence of physical inactivity and associated factors in adolescents, using a cross-sectional design with a sample of 1,455 adolescents (741 females). Data were collected using a questionnaire consisting of socio-demographic, perceptual, and behavioral variables. Physical activity was estimated with the Physical Activity Questionnaire for Older Children and Adolescents. Prevalence of physical inactivity was 68% (95%CI: 65.6%-70.4%). The following variables remained associated with physical inactivity in the adjusted analysis (p < 0.05): living in an apartment, female gender, older adolescents, lower self-rated physical activity compared to peers, low perception of maternal physical activity, passive commuting to school, non-participation in physical education at school, non-enjoyment of physical education classes, and limited involvement in other types of physical exercise besides physical education at school. There were a high proportion of inactive adolescents. Strategies to prevent physical inactivity in adolescents should be elaborated with a central role for the school and family. PMID- 24233038 TI - Breast cancer incidence and mortality in women under 50 years of age in Brazil. AB - Many countries have reported an increase in breast cancer incidence in young women. The current study's objective was to explore breast cancer distribution in women less than 50 years of age in Brazil. A descriptive study on breast cancer incidence (selected cities) and mortality (Brazil and selected cities) in 2002 2004 was carried out, and the results were compared with those from other countries. The study also analyzed the trend in hospital morbidity and incidence rates for breast cancer. Porto Alegre (Rio Grande do Sul State) showed the highest incidence rates (17.9 and 165.5/100,000 in the 15-39 and 40-49-year age strata, respectively). Regarding mortality, Belo Horizonte (Minas Gerais State) showed the highest rate in the 15-39-year group and Porto Alegre in the 40-49 year group (2.8 and 25.5/100,000). Hospital admissions and incidence rates for breast cancer suggest a change in epidemiological distribution. The results reveal an epidemiological pattern of breast cancer in young Brazilian women with regional distribution characteristics. PMID- 24233039 TI - [Anemia and hemoglobin level as prognostic factors of mortality in community dwelling elderly: evidence from the Bambui Cohort Study on Aging, Minas Gerais State, Brazil]. AB - The aim of this study was to examine the influence of low hemoglobin (Hb) and anemia on mortality in the elderly in a ten-year follow-up (1997-2007). Among the 1,742 elderly participants in the baseline cohort from Bambui, Minas Gerais State, Brazil, 1,322 (82.3%) were followed for an average of 8.9 years. Probability of survival was estimated by Kaplan-Meier and Cox's proportional hazard ratios (HR), and confidence intervals (95%CI) were used, considering potential confounders. Anemia and low Hb (lowest tertile) were associated with increased risk of death (HR = 2.63, 95%CI: 1.83-3.76 and HR = 1.38, 95%CI: 1.07 1.79, respectively). The results show that anemia or low Hb (regardless of a diagnosis of anemia) should be interpreted and managed as independent determinants of mortality in this elderly population. PMID- 24233040 TI - The relationship between physical aspects of quality of life and extreme levels of regular physical activity in adults. AB - This study aimed to check for any significant differences in perceived quality of life, specifically aspects of a physical nature, among volunteers who are more physically active and those less physically active in a university community. The sample consisted of 1,966 volunteers in a university community in Brazil. To assess physical activity levels, volunteers responded to the International Physical Activity Questionnaire (IPAQ), and to analyse the perception of quality of life they responded to WHOQOL-bref, which is classified into three groups according to level of physical activity, taking into account the metabolic equivalent index (MET) over a full week. For comparison, consideration was given to the first and third tertiles, respectively, namely groups of more and less active students. The results indicated that individuals who engaged in more physical activity had a more positive perception of quality of life compared to those who were less active in physical aspects related to the ability to work, energy for day-to-day activities and locomotion. PMID- 24233041 TI - [Deployment analysis of the Brazilian Breastfeeding Network: challenges and prospects for promoting breastfeeding in primary care]. AB - The article evaluates the implementation of the Brazilian Breastfeeding Network, a strategy developed by the Ministry of Health to encourage breastfeeding in primary health care. We performed an evaluation study on the implementation analysis of component 1, considering three levels (Federal, State, and Municipal). A log-frame model and matrix of indicators for the Breastfeeding Network were developed. To understand the organizational context, applying the categories analyzed by Matus Triangles and the degree of implementation of the Breastfeeding Network, we used document analysis, interviews, and focus groups. The degree of implementation was obtained by assessing the proposed activities at all three levels; municipalities were evaluated according to Ministry of Health criteria for certification of primary health care services. We identified different organizational contexts and different degrees of deployment, ranging from 18 to 100%. The study showed the influence of context on the deployment strategy, such that more favorable contexts were associated with more advanced levels of deployment. PMID- 24233042 TI - Factors associated with the prevalence of hypertension and control practices among elderly residents of Sao Paulo city, Brazil. AB - The aim of this study was to analyze the prevalence of hypertension and control practices among the elderly. The survey analyzed data from 872 elderly people in Sao Paulo, Brazil, through a cluster sampling, stratified according to education and income. A Poisson multiple regression model checked for the existence of factors associated with hypertension. The prevalence of self-reported hypertension among the elderly was 46.9%. Variables associated with hypertension were self-rated health, alcohol consumption, gender, and hospitalization in the last year, regardless of age. The three most common measures taken to control hypertension, but only rarely, are oral medication, routine salt-free diet and physical activity. Lifestyle and socioeconomic status did not affect the practice of control, but knowledge about the importance of physical activity was higher among those older people with higher education and greater income. The research suggests that health policies that focus on primary care to encourage lifestyle changes among the elderly are necessary. PMID- 24233043 TI - [Institutional violence, medical authority, and power relations in maternity hospitals from the perspective of health workers]. AB - The current article discusses institutional violence in maternity hospitals from the health workers' perspective, based on data from a study in the city of Sao Paulo, Brazil. Eighteen health workers from the public and private sectors were interviewed, including obstetricians, nurses, and nurse technicians. A semi structured interview was used with questions on professional experience and the definition of violence. The analysis revealed that these health workers acknowledged the existence of discriminatory and disrespectful practices against women during prenatal care, childbirth, and the postpartum. Examples of such practices cited by interviewees included the use of pejorative slang as a form of "humor", threats, reprimands, and negligence in the management of pain. Such practices are not generally viewed by health workers as violent, but rather as the exercise of professional authority in what is considered a "difficult" context. The institutional violence is thus trivialized, disguised as purportedly good practice (i.e., "for the patient's own good"), and rendered invisible in the daily routine of care provided by maternity services. PMID- 24233044 TI - [Knowledge of condom among adolescents: a population-based study in the semiarid region of Northeast Brazil]. AB - This study aimed to determine the prevalence of lack of knowledge on condoms and to identify associated factors among teenagers in two municipalities (counties) in Piaui State, Brazil, in mid-2008. Standardized home interviews were conducted by trained interviewers with all the teenagers (13-19 years of age). The study investigated demographic and socioeconomic characteristics and knowledge on contraception and sexually transmitted diseases (STDs). The outcome variable was lack of knowledge on male condoms. The multivariate analysis used Poisson regression with robust variance. Of the 2,241 adolescents, 18.8% claimed ignorance of male condoms. Among individuals with at least 9 years of schooling, only 4% lacked knowledge on condoms. Meanwhile, among individuals who lacked knowledge on STDs, 74% lacked knowledge on condoms. In the adjusted analysis, female gender, younger age, low schooling, not having a girlfriend, and lack of knowledge on oral contraception and STDs increased the likelihood of lack of knowledge on condoms. The data showed the urgent need for awareness-raising interventions on condom use among adolescents in these municipalities. PMID- 24233045 TI - [Neurological manifestations in riverine populations from areas exposed to mercury in the Brazilian Amazon]. AB - This study evaluated current levels of mercury exposure and sensory symptoms in adults from three riverine communities in Para State, Brazil, two of which located in the Tapajos River basin and one in the Tocantins basin. Participants in this study included 78 residents in Barreiras (Tapajos), 30 in Sao Luiz do Tapajos (Tapajos), and 49 in Furo do Maracuja (Tocantins). Total hair mercury concentrations were quantified by atomic absorption spectrophotometry, and neurological evaluation was conducted by routine examination. Mercury concentrations in the Tapajos communities were higher than those in the Tocantins (p < 0.01). Evaluation of neurological changes showed no significant difference between the communities in exposed areas and control areas for the changes observed by conventional neurological examination, except for gait deviation (p < 0.05). The study concludes that despite the mercury exposure levels, there was a low frequency of sensory alterations according to conventional neurological testing. PMID- 24233046 TI - [Determinants of dental services utilization by adults: a population-based study in Florianopolis, Santa Catarina State, Brazil]. AB - This study aimed to estimate the prevalence of dental services utilization by adults and to identify associated socioeconomic, demographic, behavioral, and self-awareness factors. A cross-sectional population-based study was conducted with adults living in the urban area of Florianopolis, Santa Catarina State, Brazil, in 2009. Associations were tested between use of dental services and predisposing, enabling, and needs-based variables. Multivariate analysis was conducted using Poisson regression with estimates of prevalence ratios and was stratified by place of last dental appointment. Prevalence of dental services utilization was 66% (95%CI: 62.9-70.7). Dental visits were 20% more frequent among women and 72% more frequent among individuals with more schooling (the latter in both public and private dental services). Individuals with private dental plans used dental services 13% more than those without. Schooling was the most important variable in predicting utilization. The study's results show the importance of monitoring associated factors in order to promote more equitable use of dental services. PMID- 24233047 TI - [Menstrual disorders among women 15 to 54 years of age in Pelotas, Rio Grande do Sul State, Brazil: a population-based study]. AB - A cross-sectional population-based study was conducted in Pelotas, Rio Grande do Sul State, Brazil, to assess the prevalence of menstrual disorders and their distribution according to parity and demographic, social, and behavioral characteristics among 1,078 women aged 15-54 years. Menstrual disorders included heavy menstrual bleeding, inter-menstrual bleeding, short cycle, long cycle, and prolonged menses. Prevalence rates and 95% confidence intervals were calculated. Overall prevalence of menstrual disorders was 46.4% (43.3-49.4). The most prevalent disorder was heavy menstrual bleeding (23.2%; 20.5-25.8), followed by short cycle (19.2%; 16.6-21.8), long cycle (14.8%; 12.7-16.9), inter-menstrual bleeding (11.1%; 9.1-13.2), and prolonged menses (7.9%; 6.3-9.4). Menstrual disorders are frequent in the population and are associated with age 35 years or older, low schooling, high parity, tubal ligation, and smoking. PMID- 24233048 TI - Clinical and demographic differences between voluntary and involuntary psychiatric admissions in a university hospital in Brazil. AB - To assess the frequency of involuntary psychiatric hospitalizations from 2001 to 2008 and to determine associated clinical and socio-demographic characteristics, a retrospective cohort study was conducted. Adult admission data were collected from a university hospital in Brazil. Hospitalizations were classified as voluntary (VH) or involuntary (IH). Groups were compared using chi-square test for categorical variables and Mann-Whitney test for continuous non-parametric variables. The relative risk of certain events was estimated by the odds ratio statistic. Of 2,289 admissions, 13.3% were IH. The proportion of IH increased from 2.5% to 21.2% during the eight year period. IH were more frequently associated with female gender, unmarried status, unemployment, and more than 9 years of schooling. Psychotic symptoms were more common among IH. There were no differences in age, duration of hospitalization, or rate of attendance at first appointment after hospital discharge. Understanding of the characteristics associated with IH is necessary to improve the treatment of psychiatric disorders. PMID- 24233052 TI - Services for adolescents with psychiatric disorders: 12-month data from the National Comorbidity Survey-Adolescent. AB - OBJECTIVE: This study examined 12-month rates of service use for mental, emotional, and behavioral disorders among adolescents. METHODS: Data were from the National Comorbidity Survey Adolescent Supplement (NCS-A), a survey of DSM-IV mental, emotional, and behavioral disorders and service use. RESULTS: In the past 12 months, 45.0% of adolescents with psychiatric disorders received some form of service. The most likely were those with ADHD (73.8%), conduct disorder (73.4%), or oppositional defiant disorder (71.0%). Least likely were those with specific phobias (40.7%) and any anxiety disorder (41.4%). Among those with any disorder, services were more likely to be received in a school setting (23.6%) or in a specialty mental health setting (22.8%) than in a general medical setting (10.1%). Youths with any disorder also received services in juvenile justice settings (4.5%), complementary and alternative medicine (5.3%), and human services settings (7.9%). Although general medical providers treated a larger proportion of youths with mood disorders than with behavior disorders, they were more likely to treat youths with behavior disorders because of the larger number of the latter (11.5% of 1,465 versus 13.9% of 820). Black youths were significantly less likely than white youths to receive specialty mental health or general medical services for mental disorders. CONCLUSIONS: Findings from this analysis of NCS-A data confirm those of earlier, smaller studies, that only a minority of youths with psychiatric disorders receive treatment of any sort. Much of this treatment was provided in service settings in which few providers were likely to have specialist mental health training. PMID- 24233054 TI - Epigenetic regulation by long noncoding RNAs in plants. AB - Many eukaryotes, including plants, produce a large number of long noncoding RNAs (lncRNAs).Growing number of lncRNAs are being reported to have regulatory roles in various developmental processes.Emerging mechanisms underlying the function of lncRNAs indicate that lncRNAs are versatile regulatory molecules. They function as potent cis- and trans-regulators of gene expression, including the formation of modular scaffolds that recruit chromatin-modifying complexes to target chromatin. LncRNAs have also been reported in plants. Here, we describe our current understanding on potential roles of lncRNA in plants. PMID- 24233053 TI - Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells. AB - The mammalian genome harbors thousands of long noncoding RNA (lncRNA) genes. Recent studies have indicated the involvement of several of these lncRNAs in the regulation of gene expression. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control,to post-transcriptional regulation. lncRNAs are localized in various subcellular compartments, and major proportion of these are retained in the cell nucleus and could be broadly classified as nuclear-retained lncRNAs (nrRNAs). Based on the identified functions,members of the nrRNAs execute diverse roles, including providing architectural support to the hierarchical subnuclear organization and influencing the recruitment of chromatin modifier factors to specific chromatin sites. In this review, we will summarize the recently described roles of mammalian nrRNAs in controlling gene expression by influencing chromatin organization, transcription,pre-mRNA processing, nuclear organization, and their involvement in disease. PMID- 24233055 TI - Robust analysis of synthetic label-free DNA junctions in solution by X-ray scattering and molecular simulation. AB - Structural analysis of branched DNA molecules (BDM) is important as model systems for DNA junctions and also as building units for DNA assembly. Although there have been efforts to study the structures of BDM, label-free solution structures have not been well determined yet. Here, we used a combination of synchrotron based experimental tools and computational simulation to study the global structures of label-free BDM in solution. Overall structures of 3-arm and 4-arm BDM were revealed as an asymmetric T(or Y)-shape and a distorted X-shape, respectively. The internal structures of the DNA double helix were shown to have a canonical B-form for both the BDM. We also reconstructed the thermal denaturation process of BDM by determining the transient global structures over a wide range of temperatures. The proposed high-resolution structures of BDM are expected to provide fundamental information for studies of the biological function of junction DNAs and DNA assembly. PMID- 24233056 TI - Are we overestimating the loss of beta cells in type 2 diabetes? AB - AIMS/HYPOTHESIS: Previous work has demonstrated that beta cell amount (whether measured as beta cell mass, beta cell volume or insulin-positive area) is decreased in type 2 diabetes; however, recent findings suggest that mechanisms other than death may contribute to beta cell failure in this disease. To better characterise beta cell mass and function in type 2 diabetes, we performed morphological, ultra-structural and functional studies using histological samples and isolated islets. METHODS: Pancreases from ten non-diabetic (ND) and ten matched type 2 diabetic organ donors were studied by insulin, glucagon and chromogranin A immunocytochemistry and electron microscopy (EM). Glucose stimulated insulin secretion was assessed using isolated islets and studies were performed using independent ND islet preparations after 24 h exposure to 22.2 mmol/l glucose. RESULTS: Immunocytochemistry showed that the fractional islet insulin-positive area was lower in type 2 diabetic islets (54.9 +/- 6.3% vs 72.1 +/- 8.7%, p < 0.01), whereas glucagon (23.3 +/- 5.4% vs 20.2 +/- 5.3%) and chromogranin A (86.4 +/- 6.1% vs 89.0 +/- 5.5%) staining was similar between the two groups. EM showed that the proportion of beta cells in type 2 diabetic islets was only marginally decreased; marked beta cell degranulation was found in diabetic beta cells; these findings were all reproduced after exposing isolated ND islets to high glucose. Glucose-stimulated insulin secretion was 40-50% lower from type 2 diabetic islets (p < 0.01), which again was mimicked by culturing non diabetic islets in high glucose. CONCLUSIONS/INTERPRETATION: These results suggest that, at least in subgroups of type 2 diabetic patients, the loss of beta cells as assessed so far might be overestimated, possibly due to changes in beta cell phenotype other than death, also contributing to beta cell failure in type 2 diabetes. PMID- 24233057 TI - Enzymatic hydrolysis of molecules associated with bacterial quorum sensing using an acyl homoserine lactonase from a novel Bacillus thuringiensis strain. AB - N-acyl homoserine lactones are key components of quorum sensing, the bacterial communication system. This communication mechanism regulates the expression of genes, including those involved in virulence and biofilm formation. This system can be interrupted by the action of enzymes that hydrolyze the signaling molecules. In this work, we studied the enzymatic properties of a recombinant AHL lactonase from Bacillus thuringiensis strain 147-11516, using substrates with acyl chains of different length (C4-HSL, C6-HSL, C7-HSL, C8-HSL and C10-HSL), we also investigated the effect of pH (5.0-9.0), temperature (20-70 degrees C), concentration of monovalent, divalent and trivalent metals ions (0.2 and 2.0 mM) and EDTA. The results showed that the recombinant AHL-lactonase had biological activity in alkaline pH conditions (8.0) and high temperature (47 % of hydrolyzed substrate at 60 degrees C). The recombinant AHL-lactonase has activity on substrates with different acyl chain length. However, the activity of the recombinant enzyme was decreased in the two concentrations of all metal ions evaluated but was not inhibited by EDTA. The affinity of the enzyme for all substrates tested and its performance, in the evaluated conditions, suggest that the AHL-lactonase from B. thuringiensis strain 147-11516 could be used as a strategy for disruption of the Gram-negative bacteria communication system under normal and challenging conditions. PMID- 24233058 TI - Contralateral delayed epidural hematoma following intracerebral hematoma surgery. AB - BACKGROUND: Delayed epidural hematoma (EDH) is an uncommon finding in patients after intracranial hematomas evacuation. It occurs in 6.7-7.4% of cases. A total of 29 reports were found in literature. Between them were no cases of delayed contralateral EDH after intracerebral hematoma evacuation. CASE DESCRIPTION: This paper represents a clinical case of a 28-year-old male patient with opened penetrating head injury, who underwent left frontal lobe intracerebral hematoma evacuation and one day later a contralateral EDH was found and successfully surgically treated. CONCLUSION: Contralateral EDH is a life-threatening neurosurgical emergency case, which can occur during first 24 hours after decompressive craniectomy. Control CT scans must be performed next day after the operation to verify and treat contralateral EDH timely. PMID- 24233059 TI - A 1,3-amino group migration route to form acrylamidines. AB - A novel 1,3-amino group migration strategy for the synthesis of acrylamidines is presented. Cu(i) catalyzed reaction of N,N-disubstituted propargylamine with tosylazide generates a highly reactive ketenimine intermediate which is trapped by a tethered amino group leading to the rearrangement reaction. PMID- 24233060 TI - Dexamethasone otoprotection in a multidose cisplatin ototoxicity mouse model. AB - OBJECTIVE: To develop a murine model for multidose administration of cisplatin that produces significant hearing threshold elevations and to use this model to assess the protective properties of intratympanic (IT) dexamethasone against cisplatin ototoxicity. STUDY DESIGN: Controlled repeated measures design. SETTING: Translational research laboratory. SUBJECTS AND METHODS: Intraperitoneal (IP) cisplatin, 2 or 3 mg/kg/day, was administered for a total of 5 or 10 days in young CBA/J mice. Pure-tone evoked auditory brainstem response (ABR) thresholds were performed on days 7, 14, 21, and 28 to evaluate hearing threshold shifts. After development of the optimal dosing regimen, 15 mice received IT dexamethasone (24 mg/ml) in one ear and IT saline in the contralateral ear. RESULTS: Significant threshold elevations were obtained for the 2 and 3 mg/kg/day 10 day groups, but both had high mortality rates and were excluded as potential multidose murine models. The 3 mg/kg/day 5 day group had a lower mortality rate and significant ABR threshold elevations for all frequencies on days 7, 14, 21, and 28. Using this dosing model, no statistically significant difference between IT dexamethasone and saline treated ears was found. CONCLUSIONS: Unlike previous single dose models, IT dexamethasone did not have an otoprotective effect in a multidose murine model of cisplatin ototoxicity. PMID- 24233061 TI - Inconclusive evidence for allergic rhinitis to predict a prolonged or chronic course of acute rhinosinusitis. AB - OBJECTIVE: To systematically review the evidence on allergic rhinitis as a predictor for a prolonged or chronic course in adult patients with acute rhinosinusitis. DATA SOURCES: Pubmed, EMBASE, and the Cochrane library. REVIEW METHODS: A systematic literature search was performed on March 15, 2013. During screening of title and abstract, 3 authors independently selected studies on allergic rhinitis as a predictor for the course of acute rhinosinusitis in adults. The reported study design was assessed for directness of evidence and risk of bias. We aimed to extract prior and posterior probabilities for a prolonged or chronic course of acute rhinosinusitis. RESULTS: Of 13,202 retrieved articles, 2 articles were eligible for study assessment. They provided a high directness of evidence but carried a high risk of bias. The studies showed an incidence of a prolonged and chronic course of, respectively, .19 (95% confidence interval [CI] .16-.23) and .05 (95% CI, .02-.13). In patients with allergic rhinitis, the incidence was .25 (95% CI, .18-.35) and .14 (95% CI, .04-.34), so the added value of allergic rhinitis to predict a prolonged course is 6% and to predict a chronic course 8%. CONCLUSION AND RECOMMENDATION: While the 2 included studies suggest that allergic rhinitis adds little to the prediction of a prolonged or chronic course in patients with acute rhinosinusitis, they carry a high risk of bias. As the available evidence does not provide grounds for different management of patients with and without allergic rhinitis, namely, according to clinical practice guidelines, both can be managed with expectant observation and symptomatic treatment. PMID- 24233062 TI - Use of the vascularized iliac-crest flap in musculoskeletal lesions. AB - Bone loss was in the past treated by several methods, such as bone distraction and the use of nonvascularized or tissue-bank bone grafts. With the advent of modern microsurgical techniques, the vascularized bone flap has been used with good results; it resolves local nutritional problems, repairs soft tissue that is often damaged by severe trauma, and treats bone loss due to tumors, pseudarthroses, and osteomyelitis. This paper reports the authors' experience with the use of vascularized iliac-crest flaps to treat orthopedic pathologies in five patients with traumatic bone loss (<10 cm), three with osteomyelitis, and three with atrophic nonunion. In all cases, the same surgeon obtained a vascularized iliac-crest flap with a pedicle based on the deep iliac circumflex artery. All flaps consolidated within a mean period of 3 months. These findings demonstrate that the use of an iliac-crest flap is a treatment option in cases of bone loss and that it is associated with good functional results and minimal donor-site morbidity. PMID- 24233064 TI - Musculoskeletal: What is different in children? Kicked another kid: pain in great toe. PMID- 24233063 TI - Protein renaturation with simultaneous purification by protein folding liquid chromatography: recent developments. AB - Protein folding liquid chromatography (PFLC)is a powerful tool for protein refolding with simultaneous purification. We review its recent progress in liquid chromatography and molecular biology, primarily involving the validation of PFLC refolding of proteins containing multiple disulphide bonds, the application of mixed-mode chromatography, PFLC in molecular biology. Representative examples are described. PMID- 24233068 TI - Delivering quality improvement: the need to believe it is necessary. AB - Quality improvement (QI) is described as being about changing the way in which patient care is delivered. It is more than just a theoretical framework against which innovations can be introduced; it is about a rigorous patient-centric approach to the design and delivery of care. In this paper we will explore some of the practicalities of delivering quality improvement in paediatrics and child health, and explain why it is an approach that we all must take. PMID- 24233065 TI - Heat-processed Panax ginseng and diabetic renal damage: active components and action mechanism. AB - Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy. PMID- 24233069 TI - Headache after lumbar puncture: randomised crossover trial of 22-gauge versus 25 gauge needles. AB - OBJECTIVES: To compare the frequency of headache and the procedure time following lumbar puncture (LP) using a 25-gauge needle compared to a 22-gauge needle. DESIGN: 4-period crossover blinded randomised controlled trial. SETTING: Oncology unit, Royal Children's Hospital, Melbourne. PATIENTS: Children aged 4-15 years at enrolment having LPs as part of their treatment for leukaemia. INTERVENTIONS: Each child was allocated a random sequence of four LPs, two with a 22-gauge and two with a 25-gauge needle. OUTCOME MEASURES: The presence of post-LP headache. Secondary outcomes included the presence of any headache, procedure time and impact of headache on the family. RESULTS: Data on 341 procedures in 93 randomised children were analysed. There was little difference in the incidence of post-LP headache between the two needle sizes (22-gauge 7.2%, 95% CI 3.8 to 12.2; 25-gauge 4.6%, 95% CI 2.0 to 8.9, p=0.3) or in the incidence of any headache (22-gauge 18% 95% CI 12.5 to 24.6; 25-gauge 15%, 95% CI 10.0 to 21.1, p=0.4). Use of the 25-gauge needle was associated with longer procedure times. The incidence of post-LP headache showed little evidence of an age effect (OR =1.1, 95% CI 0.98 to 1.3) and was higher in girls than in boys (11% vs 3%, respectively, OR=3.3, 95% CI 1.3 to 8.4, p=0.014). Fifty-five per cent of families with a child with a post-LP headache assessed the overall functional impact as moderate or severe. CONCLUSIONS: There was little difference in the occurrence of post-LP headache or any headache between procedures carried out using the 22-gauge or 25-gauge needles. Depending on the circumstances of the procedure and the experience of the operator, either gauge may be appropriate for an LP in a child. PMID- 24233070 TI - Public stigma and self-stigma: differential association with attitudes toward formal and informal help seeking. AB - OBJECTIVE: Individuals in need of psychiatric treatment often avoid seeking help because of stigma. This study examined the impact of two stigma dimensions on help-seeking attitudes. Perceived public stigma refers to discrimination and devaluation by others, and anticipated self-stigma refers to internalization of negative stereotypes about people who seek help. METHODS: Data were from the 2009 Stigma in a Global Context-Belgian Mental Health Study, in which face-to-face interviews were conducted with a representative sample of the general Belgian population. The study reported here included 728 respondents who received a vignette depicting major depression or schizophrenia. Perceived public stigma and anticipated self-stigma were measured with validated instruments. Respondents' attitudes toward help seeking were measured by the importance they assigned to care from formal and informal providers: general practitioners, psychiatrists, psychologists, family members, or friends. Multiple linear regression models were estimated. RESULTS: Respondents with higher levels of anticipated self-stigma attached less importance to care provided by general practitioners or psychiatrists, and those with higher levels of perceived public stigma rated informal help seeking as less important. The gender and the ethnicity of the person and respondents' sociodemographic characteristics had relatively little effect on help-seeking attitudes. CONCLUSIONS: Anticipated self-stigma and perceived public stigma appeared to have a differential impact on attitudes toward formal and informal help seeking. Internalization of negative stereotypes was negatively associated with the perceived importance of care from medical providers (general practitioners and psychiatrists). Awareness of stereotypes held by others deterred respondents from acknowledging the importance of informal care. PMID- 24233071 TI - Behaviour of zinc complexes and zinc sulphide nanoparticles revealed by using screen printed electrodes and spectrometry. AB - In this study, we focused on microfluidic electrochemical analysis of zinc complexes (Zn(phen)(his)Cl2, Zn(his)Cl2) and ZnS quantum dots (QDs) using printed electrodes. This method was chosen due to the simple (easy to use) instrumentation and variable setting of flows. Reduction signals of zinc under the strictly defined and controlled conditions (pH, temperature, flow rate, accumulation time and applied potential) were studied. We showed that the increasing concentration of the complexes (Zn(phen)(his)Cl2, Zn(his)Cl2) led to a decrease in the electrochemical signal and a significant shift of the potential to more positive values. The most likely explanation of this result is that zinc is strongly bound in the complex and its distribution on the electrode is very limited. Changing the pH from 3.5 to 5.5 resulted in a significant intensification of the Zn(II) reduction signal. The complexes were also characterized by UV/VIS spectrophotometry, chromatography, and ESI-QTOF mass spectrometry. PMID- 24233072 TI - Integration of utilities infrastructures in a future internet enabled smart city framework. AB - Improving efficiency of city services and facilitating a more sustainable development of cities are the main drivers of the smart city concept. Information and Communication Technologies (ICT) play a crucial role in making cities smarter, more accessible and more open. In this paper we present a novel architecture exploiting major concepts from the Future Internet (FI) paradigm addressing the challenges that need to be overcome when creating smarter cities. This architecture takes advantage of both the critical communications infrastructures already in place and owned by the utilities as well as of the infrastructure belonging to the city municipalities to accelerate efficient provision of existing and new city services. The paper highlights how FI technologies create the necessary glue and logic that allows the integration of current vertical and isolated city services into a holistic solution, which enables a huge forward leap for the efficiency and sustainability of our cities. Moreover, the paper describes a real-world prototype, that instantiates the aforementioned architecture, deployed in one of the parks of the city of Santander providing an autonomous public street lighting adaptation service. This prototype is a showcase on how added-value services can be seamlessly created on top of the proposed architecture. PMID- 24233073 TI - Plastic optical fibre sensor for spine bending monitoring with power fluctuation compensation. AB - This paper presents the implementation of power fluctuation compensation for an intensity-based optical fibre bending sensor aimed at monitoring human spine bending in a clinical environment. To compensate for the light intensity changes from the sensor light source, a reference signal was provided via the light reflection from an aluminum foil surface fixed at a certain distance from the source fibre end tips. From the results, it was found that the investigated sensor compensation technique was capable of achieving a 2 degrees resolution for a bending angle working range between 0 degrees and 20 degrees . The study also suggested that the output voltage ratio has a 0.55% diversion due to input voltage variation between 2.9 V and 3.4 V and a 0.25% output drift for a 2 h measurement. With the achieved sensor properties, human spine monitoring in a clinical environment can potentially be implemented using this approach with power fluctuation compensation. PMID- 24233074 TI - SAR image segmentation using Voronoi tessellation and Bayesian inference applied to dark spot feature extraction. AB - This paper presents a new segmentation-based algorithm for oil spill feature extraction from Synthetic Aperture Radar (SAR) intensity images. The proposed algorithm combines a Voronoi tessellation, Bayesian inference and Markov Chain Monte Carlo (MCMC) scheme. The shape and distribution features of dark spots can be obtained by segmenting a scene covering an oil spill and/or look-alikes into two homogenous regions: dark spots and their marine surroundings. The proposed algorithm is applied simultaneously to several real SAR intensity images and simulated SAR intensity images which are used for accurate evaluation. The results show that the proposed algorithm can extract the shape and distribution parameters of dark spot areas, which are useful for recognizing oil spills in a further classification stage. PMID- 24233075 TI - A wide spectral range reflectance and luminescence imaging system. AB - In this study, we introduce a wide spectral range (200-2500 nm) imaging system with a 250 MUm minimum spatial resolution, which can be freely modified for a wide range of resolutions and measurement geometries. The system has been tested for reflectance and luminescence measurements, but can also be customized for transmittance measurements. This study includes the performance results of the developed system, as well as examples of spectral images. Discussion of the system relates it to existing systems and methods. The wide range spectral imaging system that has been developed is however highly customizable and has great potential in many practical applications. PMID- 24233076 TI - Temporal and spatial properties of a yeast multi-cellular amplification system based on signal molecule diffusion. AB - We report on the spatial and temporal signaling properties of a yeast pheromone based cell communication and amplifier system. It utilizes the Saccharomyces cerevisiae mating response pathway and relies on diffusion of the pheromone alpha factor as key signaling molecule between two cell types. One cell type represents the alpha-factor secreting sensor part and the other the reporter part emitting fluorescence upon activation. Although multi-cellular signaling systems promise higher specificity and modularity, the complex interaction of the cells makes prediction of sensor performance difficult. To test the maximum distance and response time between sensor and reporter cells, the two cell types were spatially separated in defined compartments of agarose hydrogel (5 x 5 mm) and reconnected by diffusion of the yeast pheromone. Different ratios of sensor to reporter cells were tested to evaluate the minimum amount of sensor cells required for signal transduction. Even the smallest ratio, one alpha-factor secreting cell to twenty reporter cells, generated a distinct fluorescence signal. When using a 1:1 ratio, the secreted pheromone induced fluorescence in a distance of up to four millimeters after six hours. We conclude from both our experimental results and a mathematical diffusion model that in our approach: (1) the maximum dimension of separated compartments should not exceed five millimeters in gradient direction; and (2) the time-limiting step is not diffusion of the signaling molecule but production of the reporter protein. PMID- 24233077 TI - Living matter observations with a novel hyperspectral supercontinuum confocal microscope for VIS to near-IR reflectance spectroscopy. AB - A broad range hyper-spectroscopic microscope fed by a supercontinuum laser source and equipped with an almost achromatic optical layout is illustrated with detailed explanations of the design, implementation and data. The real novelty of this instrument, a confocal spectroscopic microscope capable of recording high resolution reflectance data in the VIS-IR spectral range from about 500 nm to 2.5 MUm wavelengths, is the possibility of acquiring spectral data at every physical point as defined by lateral coordinates, X and Y, as well as at a depth coordinate, Z, as obtained by the confocal optical sectioning advantage. With this apparatus we collect each single scanning point as a whole spectrum by combining two linear spectral detector arrays, one CCD for the visible range, and one InGaAs infrared array, simultaneously available at the sensor output channel of the home made instrument. This microscope has been developed for biomedical analysis of human skin and other similar applications. Results are shown illustrating the technical performances of the instrument and the capability in extracting information about the composition and the structure of different parts or compartments in biological samples as well as in solid statematter. A complete spectroscopic fingerprinting of samples at microscopic level is shown possible by using statistical analysis on raw data or analytical reflectance models based on Abeles matrix transfer methods. PMID- 24233080 TI - [Lumbopelvic fixation in posterior pelvic ring fractures and lumbosacral instability]. PMID- 24233078 TI - Biostable ssDNA aptamers specific for Hodgkin lymphoma. AB - As a "chemical antibody", oligonucleotide aptamers can specifically bind to their target molecules. However, clinical potential of aptamers in disease diagnosis is not yet fully explored. Using a tumor cell-based selection protocol, we developed single-stranded DNA aptamers for Hodgkin lymphoma (HL) tumor cells. The aptamers specifically bound to HL cells with a high affinity, reaching maximal cell binding at 10 nM final concentration. Importantly, the aptamers were able to selectively detect HL cells and did not react to other tumor or blood cells in mixed samples, indicating that the aptamers can be used as a specific probe for in vitro analysis of HL cells. Moreover, due to the inherent properties of DNA, the aptamers were stable in human serum, suggesting potential for in vivo detection of HL tumor cells. PMID- 24233081 TI - [Sacrum fractures and lumbopelvic instabilities in pelvic ring injuries: classification and biomechanical aspects]. AB - Multiplanar posterior pelvic ring instabilities are severe injuries and typically occur in the os ilium, the sacroiliac joint, the sacrum and/or in a combination of these sites. They pose challenges to the orthopedic trauma surgeon during reconstruction, particularly when these injuries are associated with multiplanar sacral fractures and involvement of the lumbosacral junction. Due to the multidirectional forces affecting the pelvic ring, one has to have basic knowledge about the mechanism of injury, its biomechanics, and the various treatment options. In the following we give an overview on injury classifications, biomechanical aspects of the injuries and various types of operative treatments and osteosynthesis techniques. PMID- 24233082 TI - [Anatomical and radiological aspects in lumbopelvic fixation]. AB - Spinal and pelvic surgery (as in neuromuscular scoliosis or unilateral highly unstable vertical sacral fractures or unstable H- or U-shaped sacral fractures) relies on lumbopelvic fixation. This technique belongs to the standard procedures for lumbosacral injuries in orthopedic surgery. Preoperatively, a CT scan with 1 mm slices is essential to detect anatomical variants and cortical narrow nesses. For optimal insertion of pedicel screws, knowledge of the pedicle diameter and length is necessary and screws should be placed convergent to each other taking into consideration the pedicle length and angle. For placement of the iliac screws exact knowledge of the anatomy is essential to avoid cortical wall perforation and neurovascular injuries. The safest screw path was determined as the bony canal between the posterior superior iliac spine (PSIS) and the anterior inferior iliac spine (AIIS). Intraoperatively, standard fluoroscopic views allow safe placement of the screws. The aim of the following manuscript is to illustrate anatomical and morphological aspects of the spine and pelvis as well as to describe important bony landmarks and optimal intraoperative C-arm views for optimal screw insertion. PMID- 24233083 TI - [Unilateral triangular lumbopelvic stabilization: indications and techniques]. AB - Operative fixation has become treatment of choice for unstable sacral fractures. Osteosynthesis for these fractures results in loss of reduction in up to 15%. Vertical sacral fractures involving the S1 facet joint (Isler 2 and 3) may lead to multidirectional instability. Multidirectional instability of the posterior pelvic ring and lumbopelvic junction may be stabilized and forces balanced by a so-called lumbopelvic triangular fixation. Lumbopelvic triangular fixation combines vertical fixation between the lumbar vertebral pedicle and the ilium, with horizontal fixation, as an iliosacral screw or a transiliacal plate osteosynthesis. The iliac screw is directed from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). Thereby, lumbopelvic fixation decreases the load to the sacrum and SI joint and transfers axial loads from the lumbar spine directly onto the ilium. Triangular lumbopelvic fixation allows early full weight bearing and therefore reduces prolonged immobilization. The placement of iliac screws may be a complex surgical procedure. Thus, the technique requires thorough surgical preparation and operative logistics. Wound related complications may occur. Preexisting Morell-Lavalee lesions increase the risk for infection. Prominent implants cause local irritation and pain. Hardware prominence and pain are markedly reduced with screw head recession into the PSIS. PMID- 24233084 TI - [Lumbopelvic stabilization for bilateral lumbosacral instabilities: indications and techniques]. AB - BACKGROUND: Bilateral lumbopelvic instabilities are rare; for the affected patients, however, they mean a severe reduction in quality of life. Optimal results can only be achieved with a well-adapted therapy algorithm that balances surgery and non-surgical procedures. OBJECTIVES: The present article addresses the indications, strategy, and techniques of bilateral lumbopelvic fixation in the operative treatment of bilateral lumbopelvic injuries and review of the literature and personal experience. RESULTS: The overall incidence of lumbosacral instabilities is low and mainly caused by high energy trauma, osteoporotic insuffiencies (e.g., primarily or secondary after long segment lumbar instrumentation), and tumors. Dramatic soft tissue injuries can occur in addition to hidden neurological impairments, and therefore it is important to diagnose and evaluate all concomitant comorbidities. The keys to success are gaining stability in the lumbosacral junction possibly combined with neuronal decompression and meaningful coordination of all disciplines, certainly challenged by finding the correct moment for surgery which is between 2 days and 2 weeks. Based on the superficial anatomy of the bony structures in the lumbosacral junction, the surgical approach has to match the pathology and should be tissue saving. CONCLUSIONS: Treatment of bilateral lumbopelvic instabilities requires an accurate examination, sophisticated therapy protocol, and a multidisciplinary approach. Surgery with a bilateral lumbopelvic fixation combined with neuronal decompression is an adequate treatment that creates early bony stability, thus, promising functional weight-bearing mobilization. PMID- 24233087 TI - Genotype specificity of the somatic embryogenesis response in cotton. AB - Thirty eight cultivars, strains, and races ofGossypium were screened for somatic embryogenesis with the protocols developed as a model forG. hirsutum L. cv. Coker 312. Four classes of response were identified; high, moderate, low, and non embryogenic. Four cultivars were further screened with 13 growth regulator regimes to determine if culture environment could change the classification or induce a higher level of response. The classification or level of response did not change. Screening of individual seedlings within a cultivar indicated that genotypic variation for embryogenesis existed. Highly embryogenic individuals were selected from cvs. Coker 312 and Paymaster 303 for use as germplasm sources for transfer of the embryogenic trait to other cultivars and genetic stocks. Only genetically responsive genotypes are amenable to the model developed for Coker 312. PMID- 24233085 TI - [Indication for primary fracture prosthesis of the shoulder]. AB - Although fractures of the proximal humerus are one of the most common osteoporotic fracture types, no generally accepted treatment algorithm exists in the current literature. For young patients with high functional demands and good rehabilitation potential, we recommend humeral head salvage therapy. If symptomatic humeral head necrosis occurs, the implantation of an anatomic endoprothesis is possible on a secondary basis. For patients with a biological age > 70 years suffering from a persisting defect of the rotator cuff along with a humeral head fracture or from a multiple fragment fracture of the humeral head, we increasingly prefer implantation of a reverse shoulder prosthesis due to good clinical results. However, because of technical aspects and a high complication rate, treatment using the reverse fracture prosthesis should be reserved for surgeons with expertise in this particular field. After analyzing the fracture- and patient-specific risk factors and performance expectations, the trauma surgeon can select the best individual therapy with the patient. PMID- 24233088 TI - Genetic transformation of grapevine cells. AB - Biovar 1 strains ofAgrobacterium tumefaciens have been used to transform a cell suspension culture ofVitis vinifera cv. Cabernet Sauvignon. Cocultivation of cultures withAgrobacterium strains bearing either the cointegrate pGV3850::1103neo, or the binary vector pGA474-68, each gave rise to kanamycin resistant tissue. The stable integration and expression of the neomycin phosphotransferase gene was confirmed by Southern blotting and enzymic assay, respectively. PMID- 24233089 TI - Somatic embryogenesis and protoplast culture in Japanese lawngrass (Zoysia japonica). AB - Embryogenic callus cultures were initiated from the mature caryopses ofZoysia japonica. Plant regeneration was through precocious germination of somatic embryos. Protoplasts were isolated from the callus and cultured in a medium solidified with agarose. Numerous calli were recovered after transferring protocolonies onto an agar medium. PMID- 24233090 TI - Transient gene expression after electroporation of protoplasts derived from embryogenic maize callus. AB - Protoplasts isolated from embryogenic callus cultures derived from immature embryos ofZea mays L. are suitable for analysis of transient gene expression using electroporation-mediated DNA transfer. Expression of introduced genes is comparable to the levels obtained with protoplasts from Black Mexican Sweet suspension cultures. Two different promoters, that directing synthesis of the 35S RNA of cauliflower mosaic virus and the maizeAdh1 promoter were placed in front of the luciferase reporter gene to assess protoplast gene expression and the impact of an intron on expression level. PMID- 24233091 TI - Mechanism and optimized conditions for PEG mediated DNA transfection into plant protoplasts. AB - Experimental conditions influencing DNA uptake efficiency by maize protoplasts in polyethyleneglycol (PEG) mediated transfection experiments have been studied systematically. The data provide evidence that the extracellular DNA is precipitated efficiently by combined action of PEG together with divalent cations and DNA is taken up by the plant protoplasts in the precipitated form. The particle size is strongly effected by the pH of the PEG solution. At optimal pH 6 6.5 a very fine and homogenous precipitate forms in presence of Ca(2+) and Mg(2+) ions and is efficiently incorporated by maize and rice protoplasts. PMID- 24233092 TI - Chitosan-elicited synthesis of callose and of coumarin derivatives in parsley cell suspension cultures. AB - In suspension cultured cells of parsley (Petroselinum crispum), chitosan elicited a rapid deposition of the 1,3-beta-glucan callose on the cell wall and a slower formation of coumarins. With cells remaining in conditioned growth medium, fully N-deacetylated chitosans and partially N-acetylated chitosans were about equally active, the potency increased with the degree of polymerization up to several thousand and addition of reduced glutathione increased the sensitivity of the cells. These results indicate common initial events in the induction of callose and coumarin synthesis although two fully independent metabolic pathways are involved. When the cells were suspended in fresh growth medium, less chitosan was required, and fully N-deacetylated chitosan became the best callose elicitor. PMID- 24233093 TI - Chimeric gene expression using maize intron in cultured cells of breadwheat. AB - High voltage electrical pulses were used to introduce the CAT reporter gene into cultured protoplasts of breadwheat,Triticum aestivum. Four DNA constructs harboring the CAT gene and the 35S or mannipine synthase promoter were tested for levels of CAT activity 40-45 hr after electroporation of protoplasts. One construct, containing a maize intron sequence between 35S and CAT sequences, conferred 30 to 185 fold greater CAT activity over the other three constructs. Data from these experiments suggest that a maize intron or sequences with similar effects may be required in DNA constructs for efficient heterologous gene expression in cultured cells of breadwheat. PMID- 24233094 TI - Somaclonal variation inLolium multiflorum L. andL. temulentum L. AB - Tiller-derived callus ofLolium multiflorum L. gave rise to 65 regenerants displaying variation in height, flowering time, chromosome number and alteration to the banding pattern of the isoenzyme superoxide dismutase. Plants were also regenerated from callus cultures initiated from immature embryos of the related inbreeding speciesLolium temulentum L. Progeny of the regenerated plants from this species displayed variation in height, flowering date, ear length and chlorophyll content. PMID- 24233095 TI - Detection and identification ofPodophyllotoxin produced by cell cultures derived from podophyllum hexandrum royle. AB - The phenylpropanoid derived lignan podophyllotoxin, occurring inPodophyllum species, is used as a starting compound for the chemical synthesis of the antitumour agents etoposide (VP-16-213) and teniposide (VM-26). At present, the availability of this lignan becomes increasingly limited. As an alternative source, cell cultures originating fromPodophyllum hexandrum Royle were initiated. Analysis of the cell extracts using different HPLC systems as well as TLC, indicated the presence of podophyllotoxin. After prepurification of the extracts by means of ITLC, the identity was confirmed by mass spectrometric analysis. Dark grown cultures accumulated considerable higher amounts of podophyllotoxin in comparison with the light-grown cultures. PMID- 24233096 TI - Difference in the location inDasycladaceae of a DNA sequence homologous to theDrosophila per locus. AB - The period (per) locus ofDrosophila melanogaster has a fundamental role on the expression of biological rhythms. A DNA sequence, which is homologous to a short region of theDrosophila per locus, has been found at different locations in various species of Dasycladaceae. InBatophora oerstedii, one of the phylogenetically oldest member of Dasycladaceae, a DNA sequence homologous to theDrosophila per locus was detected only in the chloroplast genome but not in the nuclear genome. In contrast, inAcetabularia cliftonii which in phylogeny branched off Batophora 350 million years ago, like in higher plants, theper locus homologous sequence is located in the nuclear rather than the chloroplast genome. The difference in the location of this sequence in phylogenetically separated species of the ancient unicellular and uninucleate green algae suggests gene translocation between the chloroplast genome and the nuclear genome during evolution. PMID- 24233097 TI - Increase of green plant regeneration efficiency by callus selection in Puccinellia limosa (Schur.) Holmbg. AB - Three main types of callus have been selected from seeds of salt marsh grass(Puccinellia limosa (Schur.) Holmbg.) subcultured on Murashige and Skoog medium supplemented with 2,4-dichlorophenoxyacetic acid and kinetin. Callus type I differentiated only occasionally. Callus type II produced roots but no shoots under all tested culture conditions. Both green (47 %) and albino plants have been obtained from the embryogenic callus type III. Callus type III was divided into two subtypes (greening and non-greening) according to the presence or absence of green spots. Separated greening embryogenic callus gave up to 87 % green plants, whereas non-greening callus produced only 4 %. PMID- 24233098 TI - Fertile allotetraploid from the cross betweenPhaseolus coccineus L. andPhaseolus acutifolius A. Gray. AB - As somatic hybridization and genetic transformation are not yet applicable to beans, a programme of hybridization between a male sterile line ofP. coccineus and a wild genotype ofP. acutifolius var.tenuifolius was carried out in order to introduce useful characters from the wild parent into the genome of the cultivated species. This interspecific cross is of particular interest sinceP. acutifolius is a source of resistance to many diseases, drought and high temperature. The difficulties in producing these hybrids were overcome by repeated pollinations and with the help of embryo culture. The F1 hybrid shows a high sterility which may be explained by the poor pollen quality and the presence of a chromosomic asynapsis at meiosis. Fertile allotetraploids (Co) were successfully produced in progeny from colchicine treated cuttings of F1 hybrids. Several (C2) mature seeds were harvested from selfed allotetraploid plants. PMID- 24233099 TI - Stimulation ofDaucus carota somatic embryogenesis by inhibitors of ethylene synthesis: cobalt and nickel. AB - The effects of Co(2+) and Ni(2+) on ethylene production and somatic embryogenesis by carrot (Daucus carota L.) cell cultures were studied. At concentrations of 10 MUM to 50 MUM, CoCl2 effectively inhibited ethylene production by embryogenic cultures and significantly stimulated somatic embryogenesis. The observed increase of embryo number was proportional to the inhibition level of ethylene production. However, CoCl2 had no effect when Ethephon was supplied. Nickel also reduced ethylene production, but to a slightly lesser extent than CoCl2, bringing about a lower increase in the number of somatic embryos. The role of ethylene on somatic embryogenesis is discussed. PMID- 24233100 TI - The application of the theory of planned behavior to help-seeking intention in a Chinese society. AB - PURPOSE: This study tested the efficacy of Ajzen's theory of planned behavior (TPB) in explaining intention to seek mental health services and compared the traditional TPB model with a TPB partial mediation model. It also aimed to understand factors related to intention to seek mental health services in Macao to inform local policies. METHOD: The present study consisted of two phases: (a) a pilot study to develop belief-based measures used in the main study, and (b) a cross-sectional study to investigate the application of TPB in understanding help seeking intention. In the main study, 337 Macao residents (age range 18-65) participated in a survey conducted in the community. RESULTS: The TPB partial mediation model was better than the traditional TPB model in explaining help seeking intention in Macao. The model also suggested that attitude, subjective norm, and perceived behavioral control were all significant predictors of help seeking intention. However, symptom severity, prior help-seeking, and gender did not significantly directly predict help-seeking intention. CONCLUSION: Preference for the TPB partial mediation model may be culturally relevant. The implications of the findings are discussed in relation to the salient beliefs about help seeking. Limitations and recommendations for future research are provided. PMID- 24233101 TI - Sulfur-selenium-molybdenum interactions distinguish selenium hyperaccumulator Stanleya pinnata from non-hyperaccumulator Brassica juncea (Brassicaceae). AB - Long-term sulfate, selenate and molybdate accumulation and translocation were investigated in two ecotypes of Stanleya pinnata and non-hyperaccumulator Brassica juncea under different levels of applied sulfate and selenate. Morphological differences were observed between the ecotypes of S. pinnata, but few differences in selenium (Se) and sulfur (S) accumulation were measured. Se-to S ratios were nearly identical between the ecotypes under all treatments. When compared with B. juncea, several unique trends were observed in the hyperaccumulators. While both S. pinnata ecotypes showed no significant effect on Se content of young leaves when the supplied sulfate in the growth medium was increased tenfold (from 0.5 to 5 mM), the Se levels in B. juncea decreased 4- to 12-fold with increased sulfate in the growth medium. Furthermore, S. pinnata's S levels decreased slightly with high levels of supplied Se, suggesting competitive inhibition of uptake, while B. juncea showed higher S levels with increasing Se, possibly due to up-regulation of sulfate transporters. Both ecotypes of S. pinnata showed much larger Se concentrations in young leaves, while B. juncea showed slightly higher levels of Se in older leaves relative to young. Molybdenum (Mo) levels significantly decreased in S. pinnata with increasing sulfate and selenate in the medium; B. juncea did not show the same trends. These findings support the hypothesis that S. pinnata contains a modified sulfate transporter with a higher specificity for selenate. PMID- 24233102 TI - Limits to ambulatory displacement of coconut mites in absence and presence of food-related cues. AB - Ambulatory movement of plant-feeding mites sets limits to the distances they can cover to reach a new food source. In absence of food-related cues these limits are determined by survival, walking activity, walking path tortuosity and walking speed, whereas in presence of food the limits are also determined by the ability to orient and direct the path towards the food source location. For eriophyoid mites such limits are even more severe because they are among the smallest mites on earth, because they have only two pairs of legs and because they are very sensitive to desiccation. In this article we test how coconut mites (Aceria guerreronis Keifer) are constrained in their effective displacement by their ability to survive in absence of food (meristematic tissue under the coconut perianth) and by their ability to walk and orient in absence or presence of food related cues. We found that the mean survival time decreased with increasing temperature and decreasing humidity. Under climatic conditions representative for the Tropics (27 degrees C and 75 % relative humidity) coconut mites survived on average for 11 h and covered 0.4 m, representing the effective linear displacement away from the origin. Within a period of 5 h, coconut mites collected from old fruits outside the perianth moved further away from the origin than mites collected under the perianth of young fruits. However, in the presence of food-related cues coconut mites traveled over 30 % larger distances than in absence of these cues. These results show that ambulatory movement of eriophyoid mites may well bring them to other coconuts within the same bunch and perhaps also to other bunches on the same coconut palm, but it is unlikely to help them move from palm to palm, given that palms usually do not touch each other. PMID- 24233103 TI - Appropriate loads for peak-power during resisted sprinting on a non-motorized treadmill. AB - The purpose of this study was to determine the load which allows the highest peak power for resisted sprinting on a non-motorized treadmill and to determine if other variables are related to individual differences. Thirty college students were tested for vertical jump, vertical jump peak and mean power, 10 m sprint, 20 m sprint, leg press 1 RM, leg press 1 RM relative to body weight, leg press 1 RM relative to lean body mass, leg press 1 RM power, and leg press power at 80% of 1 RM. Participants performed eight resisted sprints on a non-motorized treadmill, with increasing relative loads expressed as percent of body weight. Sprint peak power was measured for each load. Pearson correlations were used to determine if relationships between the sprint peak power load and the other variables were significant. The sprint peak power load had a mode of 35% with 73% of all participants having a relative sprint peak power load between 25-35%. Significant correlations occurred between sprint peak power load and body weight, lean body mass, vertical jump peak and mean power, leg press 1 RM, leg press 1 RM relative to lean body mass, leg press 1 RM power, and leg press power at 80% of 1 RM (r = 0.44, 0.43, 0.39, 0.37, 0.47, 0.39, 0.46, and 0.47, respectively). Larger, stronger, more powerful athletes produced peak power at a higher relative load during resisted sprinting on a non-motorized treadmill. PMID- 24233105 TI - Psychotropic prescribing for persons with intellectual disabilities and other psychiatric disorders. AB - OBJECTIVE: Prescribing patterns of psychotropic medication over a five-year period for Medicaid recipients (adults and children) with codiagnoses of an intellectual disability and a mental disorder were compared with patterns for those with sole mental disorder diagnoses. METHODS: Each group was identified through paid behavioral health services claims. Four classes of medications (antidepressants, antipsychotics, benzodiazepines, and mood stabilizers) were examined in paid pharmacy claims. Diagnostic categories, rates of psychotropic prescription, and polypharmacy (three or more medications concurrently for 90 days or more) were compared by age group (child or adult). RESULTS: Adults with mental disorders only (N=793 to 883; the range reflects the five study years) were prescribed antidepressants at a significantly higher rate compared with adults in the codiagnosis group (N=184 to 217). For three of the five study years, antipsychotics were prescribed to the sole-diagnosis group of adults at a significantly higher rate than to those with codiagnoses. Children in the group with codiagnoses (N=108 to 141) were prescribed mood stabilizers at a significantly higher rate than the comparison group (N=638 to 728) in all five study years. Rates of antipsychotics prescribed were not statistically different between the two groups of children. Polypharmacy rates for both adults and children were higher for the codiagnosis group compared with the group with a sole mental disorder, but the difference did not reach statistical significance. CONCLUSIONS: Psychotropic prescribing patterns in the two groups studied varied by class of medication and age. Although evidence exists for using psychotropics to treat psychopathology and challenging behaviors among individuals with intellectual disabilities, consideration of behavioral intervention alternatives and careful monitoring of psychotropic effectiveness and side effects are recommended. PMID- 24233104 TI - Involvement of host regulatory pathways during geminivirus infection: a novel platform for generating durable resistance. AB - Geminiviruses are widely distributed throughout the world and cause devastating yield losses in almost all the economically important crops. In this review, the newly identified roles of various novel plant factors and pathways participating in plant-virus interaction are summarized with a particular focus on the exploitation of various pathways involving ubiquitin/26S proteasome pathway, small RNA pathways, cell division cycle components, and the epigenetic mechanism as defense responses during plant-pathogen interactions. Capturing the information on these pathways for the development of strategies against geminivirus infection is argued to provide the basis for new genetic approaches to resistance. PMID- 24233107 TI - Trends in mortality from respiratory diseases among the elderly and the influenza vaccine intervention, 1980-2009. AB - OBJECTIVE: To evaluate mortality trends before and after the anti-influenza vaccination campaigns among the elderly in Brazil. METHODS: This was an ecological time-series study of mortality from respiratory diseases among the elderly living in the state of Sao Paulo, Brazil, in 1980 - 2009. Mortality rates were calculated using death data from the Ministry of Health's Mortality Information System and population data from the Brazilian Institute of Geography and Statistics. Polynomial regression models were used to evaluate mortality trends by sex and age group (60 - 69 years; 70 - 79, and 80 years or older) before and after the beginning of influenza vaccination campaigns. RESULTS: An increase in the respiratory mortality rates was observed in 1980 - 1998, mainly among males. The rate and velocity of the increase was higher among the older age groups. In the years following the vaccine campaigns (1999 - 2009), respiratory mortality rate trends by sex and age stabilized in Sao Paulo state. CONCLUSIONS: A greater reduction in mortality rates would be observed if vaccinal coverage against influenza were greater and more homogenous. New strategies to increase the uptake of vaccine among the elderly are needed to reach higher coverage levels, especially in municipalities with older and larger populations. PMID- 24233106 TI - Binational utilization and barriers to care among Mexican American border residents with diabetes. AB - OBJECTIVE: To assess whether U.S.-Mexico border residents with diabetes 1) experience greater barriers to medical care in the United States of America versus Mexico and 2) are more likely to seek care and medication in Mexico compared to border residents without diabetes. METHODS: A stratified two-stage randomized cross-sectional health survey was conducted in 2009 - 2010 among 1 002 Mexican American households. RESULTS: Diabetes rates were high (15.4%). Of those that had diabetes, most (86%) reported comorbidities. Compared to participants without diabetes, participants with diabetes had slightly greater difficulty paying US$ 25 (P = 0.002) or US$ 100 (P = 0.016) for medical care, and experienced greater transportation and language barriers (P = 0.011 and 0.014 respectively) to care in the United States, but were more likely to have a person/place to go for medical care and receive screenings. About one quarter of participants sought care or medications in Mexico. Younger age and having lived in Mexico were associated with seeking care in Mexico, but having diabetes was not. Multiple financial barriers were independently associated with approximately threefold-increased odds of going to Mexico for medical care or medication. Language barriers were associated with seeking care in Mexico. Being confused about arrangements for medical care and the perception of not always being treated with respect by medical care providers in the United States were both associated with seeking care and medication in Mexico (odds ratios ranging from 1.70 - 2.76). CONCLUSIONS: Reporting modifiable barriers to medical care was common among all participants and slightly more common among 1) those with diabetes and 2) those who sought care in Mexico. However, these are statistically independent phenomena; persons with diabetes were not more likely to use services in Mexico. Each set of issues (barriers facing those with diabetes, barriers related to use of services in Mexico) may occur side by side, and both present opportunities for improving access to care and disease management. PMID- 24233108 TI - Violence and social capital in post-conflict Guatemala. AB - OBJECTIVE: Violence in post-conflict Guatemala has serious public health consequences for the population. The objective of this study was to assess the relationship between violence and social capital. METHODS: Data from a cross sectional victimization survey conducted in 2008 - 2010 in Guatemala were analyzed. Two-stage proportionate sampling was used in the survey. Households (n = 1 300) were randomly sampled within a random sample of communities (n = 118) in five administrative departments. The survey collected information on the six month violence exposure of 6 335 individuals. Social capital was measured at the household level using the short version of the Adapted Social Capital Tool (SASCAT). The odds ratio for household violence exposure was estimated using multiple logistic regression. Community-level data from the latest national census were included as explanatory factors at the community level. Income, ethnicity, and social capital were included at the household level. Data were analyzed using SPSS 18.0. RESULTS: In total, 2.7% of individuals and 11.7% of households had been exposed to violence within the past six months. The multivariate analysis showed that 1) structural social capital (in this case, the level of participation in social networks and civil society) was a risk factor for violence and 2) cognitive social capital (measured as trust, norms, and sense of belonging) was a protective factor for violence. CONCLUSIONS: The opposite direction of the association between violence and structural and cognitive social capital challenges the use of social capital as a unified concept. If this finding is corroborated by other studies, structural and cognitive social capital will have to be treated as two distinctly different concepts. PMID- 24233109 TI - [Drug regulatory authorities in South America: an analysis based on organizational rules]. AB - OBJECTIVE: To describe the organization of national drug regulatory authorities (DRAs) in Argentina, Brazil, Chile, and Peru through the analysis of categories representing organizational rules. METHODS: The DRAs were selected using the following criteria: being in a South American country, having been identified as DRAs at Encuentros de Autoridades Competentes en Medicamentos de los Paises Iberoamericanos (Conferences of Ibero-American Drug Regulatory Authorities), and having good availability of electronic data regarding organizational structure and the process of drug regulation. The main source of data were websites, which were reviewed between May 2010 and March 2011. The analytical categories were: organizational structure, competencies, directionality (mission and vision statements), and forms of accountability. RESULTS: The DRAs of Argentina and Brazil functioned as autonomous agencies, while those of Chile and Peru were directly subordinated to the ministries of health. Except for the Brazilian DRA, the agencies in the other three countries were dependent on their health ministries to issue sanitary regulations. The scope of action of each DRA differed in terms of the goods and services covered, with the Peruvian DRA being the only one exclusively dedicated to the regulation of drugs. The four DRAs performed all the processes identified by the World Health Organization as essential for effective drug regulation. CONCLUSIONS: The results show an effort by the studied countries to improve their regulatory structure. Nevertheless, all four DRAs need to improve some mechanisms to ensure that, at the end of the regulatory chain, the drugs they regulate have the desired quality and safety, with more transparency in decision-making processes and social accountability. PMID- 24233110 TI - The cost-savings of implementing kangaroo mother care in Nicaragua. AB - OBJECTIVE: To examine the costs of implementing kangaroo mother care (KMC) in a referral hospital in Nicaragua, including training, implementation, and ongoing operating costs, and to estimate the economic impact on the Nicaraguan health system if KMC were implemented in other maternity hospitals in the country. METHODS: After receiving clinical training in KMC, the implementation team trained their colleagues, wrote guidelines for clinicians and education material for parents, and ensured adherence to the new guidelines. The intervention began September 2010 The study compared data on infant weight, medication use, formula consumption, incubator use, and hospitalization for six months before and after implementation. Cost data were collected from accounting records of the implementers and health ministry formularies. RESULTS: A total of 46 randomly selected infants before implementation were compared to 52 after implementation. Controlling for confounders, neonates after implementation had lower lengths of hospitalization by 4.64 days (P = 0.017) and 71% were exclusively breastfed (P < 0.001). The intervention cost US$ 23 113 but the money saved with shorter hospitalization, elimination of incubator use, and lower antibiotic and infant formula costs made up for this expense in 1 - 2 months. Extending KMC to 12 other facilities in Nicaragua is projected to save approximately US$ 166 000 (based on the referral hospital incubator use estimate) or US$ 233 000 after one year (based on the more conservative incubator use estimate). CONCLUSIONS: Treating premature and low-birth-weight infants in Nicaragua with KMC implemented as a quality improvement program saves money within a short period even without considering the beneficial health effects of KMC. Implementation in more facilities is strongly recommended. PMID- 24233111 TI - Direct and mediated associations between religious coping, spirituality, and youth violence in El Salvador. AB - OBJECTIVE: To examine the direct and mediated relationships between religious coping, spirituality, social developmental factors, and violence among high-risk and gang-involved youth in a high-crime, Latin American country. METHODS: Using a community sample of 290 high-risk and gang-involved youth in San Salvador, El Salvador, structural equation modeling was employed to examine the relationships between religious coping, spirituality, social developmental factors (e.g., antisocial bond and antisocial beliefs), and violence. RESULTS: Religious coping (beta = - 0.14, P < 0.05) and spirituality (beta = - 0.20, P < 0.01) were both significantly associated with antisocial bond. Antisocial bond, in turn, was directly associated with violence (beta = 0.70, P < 0.001) and was associated with antisocial beliefs (beta = 0.54, P < 0.001); however, the path from antisocial beliefs to violence was not statistically significant. No direct paths were identified from religiosity and spirituality to violence. The goodness-of fit statistics (root mean square error of approximation, 0.034; comparative fit index, 0.974; and Tucker-Lewis index, 0.966) suggest that the final model had acceptable fit. CONCLUSIONS: This study is among the first to shed light on the relationship between religiosity, spirituality, and youth violence in the Latin American context. Elevated levels of religious coping and spirituality are associated with less antisocial bonding, which, in turn, is associated with lower levels of violent behavior among high-risk and gang-involved Salvadoran youth. Study findings suggest that religious coping and spirituality are indirectly protective for youth violence among this high-risk population. PMID- 24233112 TI - Municipal-level covariates of health status in Brazil: a proposed method for data interpolation. AB - OBJECTIVE: To propose a method for the interpolation of yearly local-level covariates of health status that is suitable for panel data analysis of the effect of health services. METHODS: The proposed method distributes the yearly rate of growth of covariates at the regional level (e.g., state) from household survey data, and applies it to interpolate yearly data at the local level (e.g., municipality) between two consecutive census surveys. The method was applied to municipal-level socioeconomic covariates of health status in Brazil for every year between 2001 and 2009. The data was tested on a previously validated analysis of the effects of the Family Health Program on post-neonatal infant mortality in Brazil. RESULTS: A total of 895 628 values were generated for 20 socioeconomic predictors of health status. Valid data were obtained for 5 057 municipalities in the Northeast, Southeast, South, and Center-West regions of Brazil, from 2001 to 2009, covering 98.89% of the municipalities in these regions and 90.87% of municipalities in the country. A supplemental annex includes the interpolated data from 2001 to 2009, plus the 2000 and 2010 census data, for all 5 057 municipalities. An application on a fixed-effect regression model suggested that, compared to linear interpolation, the proposed method reduced multi collinearity and improved the precision of the estimates of the effects of health services. CONCLUSIONS: The advantages of the proposed interpolation method suggest that it is a feasible solution for panel data analysis of health services at the local level in Brazil and other countries. PMID- 24233113 TI - Expert consensus-building for developing guidelines: lessons learned from a dengue economics workshop. AB - A workshop with 20 experts of diverse backgrounds from five countries in the Americas was convened for two-and-a-half days in March 2012 to discuss and develop a standardized methodology for assessing the economic cost of dengue. This article discusses a number of factors that contributed to the workshop's success, including: engaging the experts at various stages of the process; convening a multidisciplinary group to reduce expert bias and provide a more comprehensive and integrated approach; facilitating guided small- and large-group discussions; developing effective cross-cultural collectivism, trust, communication, and empathy across the expert panel; establishing clear lines of responsibilities within each group of experts; breaking down the complex issues into smaller and simpler ideas; providing ample background materials in multiple languages prior to the workshop. Challenges and areas for improvement are also covered. PMID- 24233114 TI - [Intellectual development disorders in Latin America: a framework for setting policy priorities for research and care]. AB - Intellectual development disorders (IDDs) are a set of development disorders characterized by significantly limited cognitive functioning, learning disorders, and disorders related to adaptive skills and behavior. Previously grouped under the term "intellectual disability," this problem has not been widely studied or quantified in Latin America. Those affected are absent from public policy and do not benefit from government social development and poverty reduction strategies. This article offers a critical look at IDDs and describes a new taxonomy; it also proposes recognizing IDDs as a public health issue and promoting the professionalization of care, and suggests an agenda for research and regional action. In Latin America there is no consensus on the diagnostic criteria for IDDs. A small number of rehabilitation programs cover a significant proportion of the people who suffer from IDDs, evidence-based services are not offered, and health care guidelines have not been evaluated. Manuals on psychiatric diagnosis focus heavily on identifying serious IDDs and contribute to underreporting and erroneous classification. The study of these disorders has not been a legal, social science, or public health priority, resulting in a dearth of scientific evidence on them. Specific competencies and professionalization of care for these persons are needed, and interventions must be carried out with a view to prevention, rehabilitation, community integration, and inclusion in the work force. PMID- 24233115 TI - [Not Available]. PMID- 24233116 TI - Measuring the effects of the Peru's national folic acid fortification program differing methods, same goal. PMID- 24233117 TI - Effect of excess iodide on thyroid function of rainbow trout,Salmo gairdneri. AB - The acute and chronic effects of excess iodide (KI or NaI) were studied on thyroid function of rainbow trout at 11+/-1 degrees C. No Wolff-Chaikoff effect, characteristic of mammals, was observed and instead plasma L-thyroxine (T4) levels increased 6 hr after a single iodide injection. Plasma 3,5,3'-triiodo-L thyronine (T3) did not change and by 24 hr plasma T4 returned to normal. This iodide-induced elevation in plasma T4 was probably not due to toxic effects demonstrated at higher NaI or KI doses. A single iodide injection also decreased the plasma iodide distribution space, decreased the fractional rate of plasma iodide loss and completely blocked thyroidal uptake of radioiodide. Injections of iodide over a 22-day period elevated plasma iodide 200X with no mortality and no influence on plasma T4 or T3. It is concluded that: (i) apart from the transient 6h increase in plasma T4, trout thyroid function, as judged by plasma hormone levels, is insensitive to considerable iodide excess, (ii) non-invasive iodide suppression of thyroidal radioiodide recycling may be useful in kinetic studies of(125)I-labeled thyroid hormones, and (iii) fundamental differences in intrathyroidal iodine metabolism appear to exist between mammals and fish. PMID- 24233118 TI - Steroidogenic capacity of coho salmon ovarian follicles throughout the periovulatory period. AB - Coho salmon follicles obtained at various times throughout the periovulatory period were incubatedin vitro with graded amounts of partially purified salmon gonadotropin (SG-G100) for 24 h and the amounts of 17beta-estradiol, testosterone and 17alpha20beta dihydroxy-4-pregnen-3-one (17alpha20betaP) released into the media determined by radioimmunoassay. By this approach, the pattern of steroid secretion by ovarian follicles was shown to change in relation to the developmental status of the oocyte. Full-grown immature follicles produced large amounts of 17beta-estradiol but negligible amounts of testosterone and 17alpha20betaP. Both basal and gonadotropin-stimulated 17beta-estradiol production was subsequently reduced with advancing oocyte development. In contrast, the production of testosterone and 17alpha20betaP increased during the course of ovarian development with testosterone production highest in follicles with a peripheral germinal vesicle and 17alpha20betaP production highest in matured and postovulatory follicles. These data are discussed in relation to information on the preovulatory changes in circulating levels of steriod hormones in salmonids. PMID- 24233119 TI - Accumulation of waterborne selenium by rainbow trout (Salmo gairdneri), eggs, fry and juveniles. AB - The effect of waterborne selenite levels on selenium accumulated by different developmental stages of rainbow trout (Salmo gairdneri) was studied using(75)SeO 3 (=) as a tracer. All stages readily accumulated selenium at both high and low concentrations, but the rate of accumulation increased as the trout developed from the egg to the juvenile feeding stage. The low rate of selenium accumulation by embryos seemed to be related more to a lack of gills than to the presence of a chorion. The bioconcentration factor (the ratio of tissue-to-water concentrations) declined in all groups with increased waterborne selenium levels; accumulation rates appeared limited by cell permeability. At low levels of waterborne selenium (0.4ug/l), the total accumulated was small relative to existing body burdens and unlikely to contribute significantly to the nutritional requirement for selenium. High levels (45.6ug/l), however, caused considerable selenium accumulation and may be sufficient to overcome the effects of low dietary selenium. PMID- 24233120 TI - A study of goldfish oocyte meiosisin vitro: effects of 2,4-dinitrophenol and adenosine-5-triphosphate. AB - Germinal vesicle migration (GVM) and/or dissolution (GVD) were measured in goldfish oocytes, treated with 17alpha, 20beta dihydroxyprogesterone (DHP) and other compounds considered to effect the cytoskeleton and oxidative phosphorylation,in vitro. Administration of DHP reinitiated meiotic maturation, increasing GVM and GVD in goldfish oocytes. Addition of 2,4-dinitrophenol (DNP) to the incubation medium significantly inhibited DHP-induced GVM and GVD. The DNP effect was found to be partially reversible after 24 h and could be reversed fully after a further delay of approximately 24h. Treatment of goldfish oocytes with demecolcine (DE; a colchicine derivative also known as colcemid) induces GVM to the micropyle without effecting GVD; while Cytochalasin-B which inhibits microfilament polymerization impairs both GVM and GVD. Administration of DNP, significantly inhibited DE-induced GVM, suggesting that GVM as well as GVD are dependent upon the process of oxidative phosphorylation. Addition of adenosine-5' -triphosphate (ATP) at low concentrations (0.01-0.1 mM) did not effect DHP induced or DNP-inhibited GVD in goldfish oocytes. The present results are consistent with the idea that migration of the oocyte nucleus during meiosis reinitiation has an energy requirement and involves participation by the cytoskeleton. PMID- 24233122 TI - The effectiveness of mono or combined osteoporosis drug therapy against bone mineral density loss around femoral implants after total hip arthroplasty. AB - Several previous studies have reported that bone mineral density (BMD) loss around femoral implants is a common outcome, particularly in the proximal femur, after total hip arthroplasty (THA). The purpose of this study was to investigate the effectiveness of alendronate monotherapy and combined therapy using alendronate and alfacalcidol for BMD preservation around femoral implants after primary THA. This study series included 60 patients who were classified into monotherapy (alendronate alone) (n = 18), combined-therapy (alendronate and alfacalcidol) (n = 20) or non-medication (n = 22) groups. The periprosthetic BMD and profile of the biochemical markers such as bone-specific alkaline phosphatase and serum N-terminal telopeptides of type-1 collagen (NTX) were measured at 1, 12, 24 and 48 weeks after surgery. The BMD values in the region of the calcar of monotherapy and combined-therapy patients were maintained and were significantly higher than those of non-medication patients at each measurement period. The plasma levels of NTX in the monotherapy and combined-therapy groups were found to be significantly lower than those in the non-medication group at each measurement period. In conclusion, the monotherapy and combined-therapy regimens significantly prevent periprosthetic BMD loss around femoral implants, most notably in the calcar, compared to no medication. PMID- 24233123 TI - The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. AB - We investigated the effects of biologics for rheumatoid arthritis (RA) patients on bone mineral density (BMD) and bone metabolic markers (BMM), retrospectively, and also clarified the effects of bisphosphonates (alendronate or risedronate 35 mg/week) and glucocorticoids. Participants in this study comprised 219 patients with RA, including 117 patients treated with biologics (infliximab, n = 90; etanercept, n = 27) and 102 patients with conventional disease-modifying anti rheumatic drugs (DMARDs) for 1 year. Changes in BMD at the lumbar spine and total hip and BMMs [urinary type I collagen cross-linked N-telopeptide (NTX) and bone specific alkaline phosphatase] were measured. BMD of the lumbar spine in both groups and total hip BMD in the biologics group were unchanged during treatment with biologics. However, BMD of the total hip was significantly decreased in the DMARDs group (from 0.731 +/- 0.135 to 0.706 +/- 0.135 g/cm2). Patients receiving glucocorticoids without bisphosphonates showed significant decrease in BMD of the total hip compared with patients not receiving glucocorticoids or receiving glucocorticoids with bisphosphonates in both biologics and DMARDs groups. Furthermore, BMD of the lumbar spine increased (p < 0.05) for patients in the biologics group who received bisphosphonates. NTX was significantly decreased only in the biologics group. Multiple regression analysis showed that BMD and bone metabolic marker levels correlated positively with bisphosphonate and biologics use and negatively with glucocorticoid use. BMD of the total hip was maintained in the patients using biologics without glucocorticoids or with bisphosphonates, but it was not maintained in the DMARDs patients, even without glucocorticoids or with bisphosphonates. Even if biologics have protective effect against bone loss of RA patients, we should consider reducing the dose of glucocorticoids and adding bisphosphonates for the treatment of osteoporosis. PMID- 24233125 TI - Stability of Y-splitting procedure combined with hang-back recession of the rectus muscle in rabbit eyes. AB - BACKGROUND: The Y-splitting procedure has been used both to treat up-shoots and down-shoots in Duane syndrome, and as a substitute for posterior fixation suture. The Y-split is often performed in conjunction with a hang-back recession when a large amount of recession or an adjustable suture is necessary. Herein, we evaluated the stability of Y-splitting hang-back recession in the rectus muscle. METHODS: Under general anesthesia, a 5-mm hang-back recession of the superior rectus muscle (SR) with Y-splitting was performed in ten eyes from ten rabbits (hang-back group). A conventional recession was performed in the SR of the fellow eye (control group). Six weeks after the procedure, the distance between the original insertion and the recessed SR (recession amount) and the width between the nasal and temporal halves of the SR were measured. These values were compared to the measurements taken at the time of surgery. RESULTS: The hang-back group had a significantly larger forward displacement than the control group (P < 0.001 for both the nasal and temporal halves). The width change between the nasal and temporal halves was also significantly larger in the hang-back group (4.94 +/- 1.32 mm) than in the control group (1.14 +/- 0.60 mm, P < 0.001). Additionally, the Y-configuration appeared to be more collapsed in the hang-back group than in the control group. CONCLUSION: Y-splitting of the rectus muscle may be unstable when it is combined with a hang-back recession. Surgeons should consider this possibility when performing Y-splitting procedures. PMID- 24233126 TI - Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger. AB - Pathogens exert a strong selection pressure on organisms to evolve effective immune defences. In addition to individual immunity, social organisms can act cooperatively to produce collective defences. In many ant species, queens have the option to found a colony alone or in groups with other, often unrelated, conspecifics. These associations are transient, usually lasting only as long as each queen benefits from the presence of others. In fact, once the first workers emerge, queens fight to the death for dominance. One potential advantage of co founding may be that queens benefit from collective disease defences, such as mutual grooming, that act against common soil pathogens. We test this hypothesis by exposing single and co-founding queens to a fungal parasite, in order to assess whether queens in co-founding associations have improved survival. Surprisingly, co-foundresses exposed to the entomopathogenic fungus Metarhizium did not engage in cooperative disease defences, and consequently, we find no direct benefit of multiple queens on survival. However, an indirect benefit was observed, with parasite-exposed queens producing more brood when they co-founded, than when they were alone. We suggest this is due to a trade-off between reproduction and immunity. Additionally, we report an extraordinary ability of the queens to tolerate an infection for long periods after parasite exposure. Our study suggests that there are no social immunity benefits for co-founding ant queens, but that in parasite-rich environments, the presence of additional queens may nevertheless improve the chances of colony founding success. PMID- 24233127 TI - Increased brain amyloid deposition in patients with a lifetime history of major depression: evidenced on 18F-florbetapir (AV-45/Amyvid) positron emission tomography. AB - PURPOSE: The literature suggests that a history of depression is associated with an increased risk of developing Alzheimer's disease (AD). The aim of this study was to examine brain amyloid accumulation in patients with lifetime major depression using (18)F-florbetapir (AV-45/Amyvid) PET imaging in comparison with that in nondepressed subjects. METHODS: The study groups comprised 25 depressed patients and 11 comparison subjects who did not meet the diagnostic criteria for AD or amnestic mild cognitive impairment. Vascular risk factors, homocysteine and apolipoprotein E (ApoE) genotype were also examined. The standard uptake value ratio (SUVR) of each volume of interest was analysed using whole the cerebellum as the reference region. RESULTS: Patients with a lifetime history of major depression had higher (18)F-florbetapir SUVRs in the precuneus (1.06 +/- 0.08 vs. 1.00 +/- 0.06, p = 0.045) and parietal region (1.05 +/- 0.08 vs. 0.98 +/- 0.07, p = 0.038) than the comparison subjects. Voxel-wise analysis revealed a significantly increased SUVR in depressed patients in the frontal, parietal, temporal and occipital areas (p < 0.01). There were no significant associations between global (18)F-florbetapir SUVRs and prior depression episodes, age at onset of depression, or time since onset of first depression. CONCLUSION: Increased (18)F-florbetapir binding values were found in patients with late-life major depression relative to comparison subjects in specific brain regions, despite no differences in age, sex, education, Mini Mental Status Examination score, vascular risk factor score, homocysteine and ApoE epsilon4 genotype between the two groups. A longitudinal follow-up study with a large sample size would be worthwhile. PMID- 24233128 TI - EJNMMI Physics--access is open for open access. PMID- 24233129 TI - The overlap in the genetic pathogenesis of ulcerative colitis and irritable bowel syndrome. PMID- 24233130 TI - Trigeminocardiac reflex in neurosurgical practice: Report of two new cases. AB - BACKGROUND: Systemic hypotension, cardiac dysrhythmia especially bradycardia, apnea, and gastric hypermotility occurring presumably after stimulation of any of the sensory branches of trigeminal nerve are coined as trigeminocardiac reflex (TCR). Neither enough is known about the predisposing factors in relation with the intraoperative occurrence of this life threatening reflex, nor about the exact pathophysiology of its brain stem pathway. ENCOUNTERING TWO CASES OF BRADYCARDIA AND HYPOTENSION DURING SURGERY ENCOURAGED THE AUTHORS TO: (1) report these two cases and review similar reports in the relevant literature, (2) discuss the suggested mechanisms for such an event, and (3) report the result of a prospective cohort of precisely checked cases in a sister article, to remind the younger neurosurgical community of a possible and bothering even mortal, but avoidable complication in their everyday practice. CASE DESCRIPTION: The first case was a 71-year-old male who developed bradycardia and hypotension while packing his large sella tursica with autologous fat after removing a large nonfunctional pituitary adenoma transsphenoidally to prevent cerebrospinal fluid leakage. The changes in his vital signs were detected and controlled rapidly. The second case was a 52-year-old female who underwent right pterional craniotomy for right clinoidal meningioma. She developed severe bradycardia and hypotension after skin closure completed and just when the subgaleal drain was connected to the aspirating bag and negative pressure maintained in the subgaleal region. Both cases could be managed successfully after on time detection of such life threatening complication and proper management. CONCLUSION: WE DO NOT INTEND ONLY TO ADD TWO NEW CASES OF TCR OCCURRING IN THE PERIOPERATIVE PERIOD IN NEUROSURGICAL PRACTICE, BUT WE WISH TO RAISE THE QUESTION: (a) what could be the predisposing factors for development of such issue for better handling of the problem and (b) stress upon careful continuous mapping of the vital signs during surgery and even till very late after operation. PMID- 24233131 TI - Evaluation of a newly designed flow diverter for the treatment of intracranial aneurysms in an elastase-induced aneurysm model, in New Zealand white rabbits. AB - INTRODUCTION: In this study, we analyzed angiographic and histologic aneurysm occlusion of a newly designed flow-diverting device. Visibility and flexibility, as well as occlusions of side branches and neointimal proliferation were also evaluated. METHODS: Aneurysms were induced in 18 New Zealand white rabbits and treated with a braided, "closed-loop-designed" device of nitinol. Additional devices were implanted in the abdominal aorta to cover the origin of branch arteries. Angiographic follow-ups were performed immediately after placement of the device, after 3 months (n = 9) and 6 months (n = 9). The status of aneurysm occlusion (using a five-point scale) and the patency of branch arteries were assessed. RESULTS: Aneurysm occlusion rates were noted as grade 0 in 2 (11 %), grade I in 1 (6 %), grade II in 1 (6 %), grade III in 9 (50 %), and grade IV in 5 (28 %) of 18 aneurysms, respectively, indicating a complete or near-complete occlusion of 78 % under double antiplatelet therapy. Aneurysm occlusion was significantly higher at 6 months follow-up (P = 0.025). Radiopaque markers provided excellent visibility. Limited device flexibility led to incomplete aneurysm neck coverage and grade 0 occlusion rates in two cases. Distal device occlusions were found in three cases, most likely due to an extremely undersized vessel diameter in the subclavian artery. No case of branch artery occlusion was seen. Intimal proliferation and diameter stenosis were moderate. CONCLUSION: The tested flow diverter achieved near-complete and complete aneurysm occlusion under double antiplatelet therapy of elastase-induced aneurysms in 78 %, while preserving branch arteries. PMID- 24233132 TI - Chloroplast targeting ofneomycin phosphotransferase II with a pea transit peptide in electroporated barley mesophyll protoplasts. AB - Routine methods for stable gene transfer to cereals are not yet available. To be able to study chloroplast targeting in barley (Hordeum vulgare L.) cells, the expression of recombinant genes was assayed in barley mesophyll protoplasts after electroporation of DNA. The CaMV 35S transcript promoter was attached to a chimeric gene consisting of a pea RuBisCo small subunit transit peptide coding sequence (tp) and the gene coding for neomycin phosphotransferase II (nptII). As a control, a construction with no transit peptide coding segment was used. 48 hours after electroporation, a fraction of the protoplasts was lysed and intact chloroplasts were isolated. Protoplasts electroporated with either of the gene constructions showed strong NPTII activity. However, enzyme activity was detected in chloroplasts only when thetp-nptII gene construction was used. Protease treatment of the chloroplasts confirms that the pea RuBisCo small subunit transit peptide is targeting the NPTII polypeptide into the chloroplasts, subsequent to the synthesis of the hybrid precursor in barley cells. PMID- 24233133 TI - Abscisic acid: a role in shoot enhancement from loblolly pine (Pinus taeda L.) cotyledon explants. AB - Enhancement of shoot regeneration from loblolly pine (Pinus taeda L.) cotyledon explants was studied by addition of abscisic acid (ABA) to Gresshoff-Doy (GD) shoot induction medium containing benzylaminopurine (BA) and naphthaleneacetic acid (NAA). Addition of ABA (10(-7) M) doubled the morphogenic area of cotyledons and increased the fresh weight of cotyledon explants by 40 to 45% after 4 weeks. A 4-week exposure to ABA resulted in a larger morphogenic area per cotyledon than 3, 2, or 1 week(s) respectively. The enhancement by ABA was related to the explant seed source and was not increased by prolonged exposure. Compared to controls, shoot number was enhanced by 31% and 56% with 2 and 4 weeks of ABA (10( 7) M) exposure, respectively. Abscisic acid has a role in enhancing shoot morphogenesis in loblolly pine. PMID- 24233134 TI - The effect of presumptive polyadenylation signals on the expression of the CAT gene in transgenic tobacco. AB - Promoter::gene fusions which differed only in the presumed polyadenylation signals attached to the 3' end of the gene, have been used to examine the effect of these signals on expression of the gene in protoplasts and in transgenic plants. The gene constructs were comprised of the 35S promoter, the chloramphenicol acetyl transferase (CAT) gene and DNA sequences carrying the presumed polyadenylation signals of the nopaline synthase (nos) gene or of transcript 7 (T-7) from the T-DNA ofAgrobacterium. Our results show that levels of gene expression were not significantly affected by the orientation or absence of these sequences. We therefore suggest that the practice of cloning presumptive polyadenylation sequences at the 3' end of a gene for expression in plants may be unnecessary. PMID- 24233135 TI - Somaclonal variation in soybean plants regenerated from tissue culture. AB - Callus cultures of soybean (Glycine max (L.) Merr.) genotypes PI 88788, PI 438489B, and cultivar Bedford were initiated in vitro from seedling explants consisting of the cotyledonary node plus epicotyl from germinated mature seed. Plants were regenerated from these callus cultures and subsequently evaluated for qualitative variation in three to four subsequent generations. Variant phenotypes observed that have not been previously reported from tissue culture include lanceolate leaves, leaf variegation (chimeral variegated plants), pod variegation on otherwise normal plants, and change in growth habit from indeterminate to determinate. The lanceolate leaf, chimeral variegated plant, and change from indeterminate to determinate growth habit characters were inherited through at least three generations (R0-R2), and segregation occurred in each generation. Pod variegation was inherited through the two generations tested thus far and segregation occurred in each generation. No variation was observed in control plants derived from normal seed. Variants appeared more frequently in regenerants from PI 88788 and PI 438489B than from Bedford. These results confirm and extend the finding that certain tissue culture techniques may be used to induce novel plant formation from somatic tissue of soybean. PMID- 24233136 TI - Initiation of embryogenic callus and suspension cultures of eastern white pine (Pinus strobus L.). AB - Embryogenic callus and suspension cultures of eastern white pine (Pinus strobus) have been obtained. The whole female gametophyte was plated on a medium containing 50 mg/l glutamine, 500 mg/l casein hydrolysate, 3% sucrose, 2 mg/1 2,4 D, 1 mg/1 BA and 0.2% Gelrite as a solidifying agent. Embryogenic calli could be seen as early as 5 days following culture. Histological studies indicate proliferation of pre-existing embryogenic tissue in the corrosion cavity followed by extrusion of embryogenic callus through the micropylar end of the gametophyte. Embryogenic suspension cultures were obtained by placing embryogenic callus into liquid medium. Embryogenic suspension cultures were subcultured weekly and proliferated as early-stage embryos with attached suspensors. Embryo development was obtained following transfer of the embryogenic tissue to an auxin-free medium containing 50 mM glutamine, 38 MUM abscisic acid, and 6% sucrose. Although embryo development could be consistently obtained, whole plants have not yet been recovered from these somatic embryos. PMID- 24233137 TI - Triglycerides in embryogenic conifer calli: a comparison with zygotic embryos. AB - Triglycerides in developing zygotic embryos of Norway spruce and loblolly pine were found to accumulate continuously during the course of development, comprising nearly 50% of the fresh weight of a mature embryo. Embryogenic calli of these two species contained dramatically lower levels of triglycerides. Abscisic acid treatments promoted both embryo production and triglyceride accumulation in Norway spruce cultures. A method used to determine triglyceride levels in human serum, commercially available in kit form, was adapted for use with plant tissues. Low levels of triglycerides in the cultured tissues may be related to difficulties in the development and germination of conifer somatic embryos. PMID- 24233138 TI - The effect of gelling agents on plaunotol accumulation in callus cultures ofCroton sublyratus Kurz. AB - Callus cultures established from the leaves ofCroton sublyratus Kurz (Euphorbiaceae) contained little or no plaunotol on various media with different hormone combinations. Plaunotol accumulation was observed in calli which were cultured in media with increasing concentrations of gelling agents, especially gellan gum and agarose. The accumulation was observed within three weeks after transfer to the medium and was accompanied by chlorophyll increase, tracheid development and slow growth. Light and increasing concentration of gelling agents were observed to be indispensable for plaunotol accumulation in the callus. PMID- 24233139 TI - Toxicity of antibiotics on zygotic embryos of white spruce (Picea glauca) cultured in vitro. AB - The toxicity of kanamycin, hygromycin B, geneticin, methotrexate and cefotaxime on zygotic embryos ofPicea glauca was studied. Embryos placed on bud induction medium produced approximately 20 adventitious buds per embryo under control conditions. Addition of antibiotics reduced the number of bud-forming embryos. Using the percentage of embryos with buds as an indication of antibiotic toxicity, two-day-old explants were found to be more sensitive than nine-day-old. Kanamycin toxicity was enhanced by cefotaxime and this effect increased with increases in concentration of either antibiotic. Although no morphological difference was observed after 21 days, embryos growing on medium containing 20 MUg ml(-1) kanamycin showed a decrease of 73% in dry weight and 23% in protein content per embryo when compared to control embryos. Similarly, a decrease of 38% in dry weight and 40% in protein content per embryo was found in embryos on medium containing 300 MUg ml(-1) cefotaxime. PMID- 24233140 TI - Plant regeneration from immature embryos of peanut. AB - Plant regeneration from immature embryos of peanut (Arachis hypogaea L.) can be accomplished through somatic embryogenesis. The highest frequency of somatic embryo formation occurred on B5 medium plus 0.5-1.0 mg/l picloram. Shoots and plants developed from the somatic embryos only after extended culture on basal medium. Shoots were excised from thick embryonic roots and rerooted on Murashige and Skoog medium containing half the normal concentration of inorganic salts. This technique should be useful for the production of interspecific hybrid plants from immatureArachis embryos. PMID- 24233141 TI - Origin of somatic embryos from repetitively embryogenic cultures of walnut (Juglans regia L.): Implications forAgrobacterium-mediated transformation. AB - Early stages of somatic embryo development from embryogenic cultures ofJuglans regia (Persian or English walnut) are described. Histological examination reveals that secondary somatic embryos arise from cotyledons and hypocotyls of primary embryos cultured in the dark. The embryos originate by transverse to oblique divisions of surface cells. Single-cell origin of the secondary embryos confirms the potential of the repetitive embryogenesis system forAgrobacterium-mediated transformation and regeneration of non-chimeric, transgenic walnut plants. PMID- 24233142 TI - Hormone-free medium will support callus production and subsequent shoot regeneration from whole plant leaf explants in some sugarbeet (Beta vulgaris L.) populations. AB - Sugarbeet plants representing 14 of 16 germplasm sources (4 to 5 plants per source) produced callus from leaf disks on a hormone-free Murashige and Skoog based medium. Overall, 49.2% of explants from partially expanded leaves of whole plants initiated callus (53 of 74 plants tested), in an average time of 96.7 days. The time to callus was considerably longer than the 4-6 weeks observed when 1 mg/L N(6)-benzyladenine has been used in the medium. Shoots were regenerated on the hormone-free medium without subculture from callus of eight individual genotypes, representing 3 of the 14 populations that produced callus. Shoots produced by 'Gartons White Knight' and 'L53' appeared to be of somatic embryo origin. Rhizogenic calli were also produced by the same three populations that regenerated shoots. Significant differences among populations were found for frequency of root formation from leaf disks and time to callus. Variation among plants within a population was significant for four of the five traits examined. The results indicate the ease of hormone autonomization in sugarbeet, and should be of value in designing regeneration media for a wider range of beet germplasm. PMID- 24233143 TI - Callus formation from isolated sunflower (Helianthus annuus) mesophyll protoplasts. AB - Mesophyll protoplasts of the cultivated sunflower,Helianthus annuus, have been consistently found not to divide or regenerate calli, despite the efforts of several groups. In the present report, we describe the conditions for donor plant culture, protoplast isolation, and their culture that were suitable for repeated regeneration of green, nodular, vigorously growing calli from isolated sunflower mesophyll protoplasts. The best conditions for protoplast isolation employed the use of both CAYLA cellulase and CAYLA pectinase. Culture conditions were not much different from those established earlier for sunflower hypocotyl protoplasts. The most startling observation was the great variability of division frequencies between experiments even under strictly controlled, identical experimental conditions. This finding points to an important influence of a variable in the physiological state of the donor plant which is difficult to control. PMID- 24233144 TI - The influence of auxins, light and cell differentiation on solasodine production bySolanum eleagnifolium Cav. calli. AB - The effect of auxins, light and cellular production ofSolanum eleagnifolium Cav. calli were studied. 2,4-dichlorophenoxyacetic acid (4.5 MUM) was the plant growth regulator used for calli initiation and this produced the highest solasodine concentration. The solasodine concentration in darkness was significantly lower than that achieved under a photoperiod of 16 h. Differentiated tissue obtained by adequate hormonal balance (several ratios of 3-indolebutyric acid to 6 benzylaminopurine) produced higher yields of solasodine than non-differentiated tissue. 3-indolebutyric acid (2.5 MUM) and 6-benzylaminopurine (8.8 MUM) increased the productivity of solasodine by 100%. PMID- 24233145 TI - Establishment and characterization of photoautotrophic protoplast-derived cultures ofNicotiana plumbaginifolia. AB - A procedure is described for the rapid establishment of photoautotrophic protoplast-derived cultures ofNicotiana plumbaginifolia. Photoautotrophic growth was induced by lowering the glucose concentration to 2.5 g.l(-1) in the protoplast culture medium and by omitting glucose from the subsequent dilution medium. Four week-old highly viable suspensions were plated on an agar-medium without glucose in unsealed Petri dishes and kept in illuminated chambers flushed with 0.05 % or 2 % CO2. Air-grown calli had net photosynthesis rates of 1.8 and 17 MUmoles CO2.g(-1) fresh wt.h(-1) in air at 0.034 % CO2 and in air enriched with 1 % CO2, respectively. Calli grown in 2 % CO2 exhibited lower rates of net photosynthesis at the two CO2 concentrations tested (0 and 7.5 MUmoles CO2.g(-1) fresh wt.h(-1), respectively). The contribution of photosynthesis to growth was estimated to be 80 % in air-grown calli and more than 90 % in calli grown in 2 % CO2. The suitability of this photoautotrophic culture procedure is discussed with regard to the screening of photosynthetic mutants or transformants from protoplasts. PMID- 24233146 TI - High efficiency transformation ofBrassica napus usingAgrobacterium vectors. AB - An efficient procedure for obtaining transgenicBrassica napus plants usingAgrobacterium binary vectors is described. The target tissue for the transformation is the cut end of cotyledonary petioles. These tissues, when cultured with their lamina intact, show a regeneration frequency of more than 80%. The cells of this cut surface, which undergo organogenesis, are very susceptible to topical infection byAgrobacterium. The cocultivation method used does not require feeder layers or use of exogenously applied promoters of virulence. After 72h of infection withAgrobacterium the explants were transferred to selective regeneration medium. Using kanamycin (15MUg cm(-3)) for selection, transgenic plantlets emerged within 3 weeks. These plantlets which appeared on over half the explants were excised and rooted for a further 7-10 days. When the plants were large enough, leaves were taken for assay of NPT II activity using dot blots. Most of the plants surviving the selection showed substantial NPT II activity. The frequency of transformation and yield of transgenic plants was higher than in previously reported methods with this species. Southern blotting revealed that integration of the T-DNA frequently occurred in multiple copies and at multiple loci in the genome. The transgenicB. napus plants all grew normally and developed fertile flowers. The transgenic plants were self-pollinated and their progeny studied by two methods. The first was a single-embryo NPT II assay performed on developing seeds of these selfed-plants. The second was a leaf bleaching assay performed by selection of germinating seedlings of the selfed progeny. Both assays yielded segregation ratios consistent with the number of integration events indicated by Southern blots. The method should have broad application in studies of gene expression in theBrassicaceae and will be a cost effective alternative to those seeking to improveBrassica crops by introduction of foreign genes. PMID- 24233147 TI - In vitro propagation of herbaceous peony (paeonia lactiflora pall.) by a longitudinal shoot-split method. AB - A procedure for the clonal propagation ofPaeonia lactiflora Pall. cvs. Takinoyosooi and Sarah Bernhardt through shoot tip culture is described. Half strength Murashige and Shoog (1962) medium supplemented with 0.5 mg/l 6 benzylaminopurine plus 1 mg/l gibberellic acid promoted formation and growth of axillary buds. Continuous shoot multiplication was achieved by vertically splitting the shoot axis and subsequent division of elongated axillary shoots every 36 days. High frequency (57-100%) of rooting was obtained on paper-bridge liquid medium supplemented with 1 mg/l indole-3-butyric acid. Half of the rooted plantlets were established on porous soil. Thus, 700 and 300 plants of cv. Takinoyosooi and Sarah Bernhardt could be theoretically obtained from a single bud in one year. PMID- 24233148 TI - Plant regeneration from protoplasts of common buckwheat (fagopyrum esculentum). AB - Protoplasts were isolated from hypocotyls of etiolated seedlings from a diploid and the corresponding autotetraploid variety of common buckwheat (Fagopyrum esculentum). The isolated protoplasts started to divide after 4 days in culture in a modified MS medium. Maximum plating efficiency was approximately 1%. Regenerated calli derived from the tetraploid genotype developed roots easily but were recalcitrant to form shoots. Eighteen months following the initiation of cultures, tetraploid embryoids and shoots emerged after 3 weeks on an MS medium containing 0.1 mg/l gibberellic acid. PMID- 24233149 TI - Correlation of papain-like enzyme production with laticifer formation in somatic embryos of papaya. AB - A protease similar to papain was produced by somatic embryos ofCarica papaya in association with the development of laticifers containing characteristic vesicles which probably originated from the endoplasmic reticulum. In contrast to somatic embryos, a papain-like protease was not detected in either friable or compact callus cultures which failed to develop laticifers. These observations strongly suggest that the differentiation into laticifers is required for papain production in papaya. PMID- 24233150 TI - Effect of oxygen supply on berberine production in cell suspension cultures and immobilized cells ofThalictrum minus. AB - The ample supply of O2 proved to be of great importance for berberine production in cell suspension culture ofThalictrum minus, as the specific O2 consumption rate of berberine-producing cells was twice as high as that of non-producing cells. Furthermore, berberine yield increased with increases in the volumetric O2 transfer coefficient (KLa). Estimation of the optimum conditions of oxygen supply in suspension cultures and immobilized cells according to a known theoretical model assuming O2 uptake by cells to be a zero-order reaction was in good agreement with the experimental data. The O2 supply to immobilized cells could be improved by reducing the cell density and radius of the bead. PMID- 24233151 TI - Structural and morphological evolution of lead dendrites during electrochemical migration. AB - The electrochemical deposition and dissolution of lead on gold electrodes immersed in an aqueous solution of lead nitrate were studied in situ using a biasing liquid cell by transmission electron microscopy (TEM). We investigate in real time the growth mechanisms of lead dendrites as deposited on the electrodes under an applied potential. TEM images reveal that lead dendrites are developed by the fast protrusion of lead branches in the electrolyte and tip splitting. And, the fast growing tip of the dendritic branch is composed of polycrystalline nanograins and it develops into a single crystalline branch eventually. This study demonstrated unique electrochemical growth of single crystal dendrites through nucleation, aggregation, alignment and attachment of randomly oriented small grains. Additionally, we found the lead concentration in the electrolyte drastically influences the morphology of dendritic formation. PMID- 24233152 TI - Identifying patients with poststroke mild cognitive impairment by pattern recognition of working memory load-related ERP. AB - The early detection of subjects with probable cognitive deficits is crucial for effective appliance of treatment strategies. This paper explored a methodology used to discriminate between evoked related potential signals of stroke patients and their matched control subjects in a visual working memory paradigm. The proposed algorithm, which combined independent component analysis and orthogonal empirical mode decomposition, was applied to extract independent sources. Four types of target stimulus features including P300 peak latency, P300 peak amplitude, root mean square, and theta frequency band power were chosen. Evolutionary multiple kernel support vector machine (EMK-SVM) based on genetic programming was investigated to classify stroke patients and healthy controls. Based on 5-fold cross-validation runs, EMK-SVM provided better classification performance compared with other state-of-the-art algorithms. Comparing stroke patients with healthy controls using the proposed algorithm, we achieved the maximum classification accuracies of 91.76% and 82.23% for 0-back and 1-back tasks, respectively. Overall, the experimental results showed that the proposed method was effective. The approach in this study may eventually lead to a reliable tool for identifying suitable brain impairment candidates and assessing cognitive function. PMID- 24233153 TI - Neither expression of VEGF-C/D nor lymph vessel density supports lymphatic invasion as the mechanism responsible for local spread of recurrent salivary pleomorphic adenoma. AB - Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p>0.05). VEGF-D expression did not correlate with peritumoral LVD (p>0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p=0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis PMID- 24233154 TI - Leser-Trelat syndrome in malignant mesothelioma and pulmonary adenocarcinoma: is the EGFR pathway part of the syndrome? AB - The syndrome of Leser-Trelat (LT) is characterized by the sudden appearance of multiple seborrhoeic keratoses (SKs) in association with internal occult malignancy. Usually, the syndrome has been associated with adenocarcinoma, most frequently of the gastrointestinal tract and breast. The pathogenesis is unclear but might be explained by circulating tumor-associated growth factors. We present two thoracic malignancies associated with LT: adenocarcinoma of the lung (ACL) and pleural malignant mesothelioma (MM). Both malignant tumors expressed high levels of epidermal growth factor receptors (EGFR) detected by immunohistochemistry (IHC), with membranous staining on the majority of malignant cells corresponding to maximum IHC scores of 290 and 300, respectively, for the MM and the ACL. SKs revealed a universal membranous staining throughout the entire epithelium with no difference in EGFR expression between the two cases and two controls with no malignant history. By fluorescence in situ hybridization, no amplification of the EGFR gene in malignant tumors as well as in SK lesions was observed. Further investigations are needed to see whether tumor-associated EGFR ligands/EGFR autocrine loops in malignant cells expressing high levels of EGFR protein on the surface might play a role for the development of SKs, as well as for the growth of malignant tumors in LT. PMID- 24233155 TI - Antiproliferative and apoptosis-inducing activity of an oxidovanadium(IV) complex with the flavonoid silibinin against osteosarcoma cells. AB - Flavonoids are a large family of polyphenolic compounds synthesized by plants. They display interesting biological effects mainly related to their antioxidant properties. On the other hand, vanadium compounds also exhibit different biological and pharmacological effects in cell culture and in animal models. Since coordination of ligands to metals can improve or change the pharmacological properties, we report herein, for the first time, a detailed study of the mechanisms of action of an oxidovanadium(IV) complex with the flavonoid silibinin, Na2[VO(silibinin)2].6H2O (VOsil), in a model of the human osteosarcoma derived cell line MG-63. The complex inhibited the viability of osteosarcoma cells in a dose-dependent manner with a greater potency than that of silibinin and oxidovanadium(IV) (p < 0.01), demonstrating the benefit of complexation. Cytotoxicity and genotoxicity studies also showed a concentration effect for VOsil. The increase in the levels of reactive oxygen species and the decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of the complex. Besides, the complex caused cell cycle arrest and activated caspase 3, triggering apoptosis as determined by flow cytometry. As a whole, these results show the main mechanisms of the deleterious effects of VOsil in the osteosarcoma cell line, demonstrating that this complex is a promising compound for cancer treatments. PMID- 24233157 TI - Genetic structure of a phytophagous mite species affected by crop practices: the case of Tetranychus urticae in clementine mandarins. AB - Tetranychus urticae Koch is a cosmopolitan mite considered as the most polyphagous species among spider mites. This mite is a key pest of clementine mandarins in Eastern Spain, where Spanish clementine production concentrates. Crop management practices can affect the population dynamics of this mite and, consequently, its impact on the orchard. Microsatellite markers were used to study mite population genetics from two commercial orchards which had been managed differently following Integrated Pest Management (IPM) or Organic Pest Management (OPM) schemes during four consecutive years. A multiplex system including 20 microsatellite loci was designed specifically and allowed an efficient and inexpensive genotyping of individual mites. We found that the IPM population had a stronger fluctuation of population structure and higher genetic diversity compared to OPM population. Thus, our study concludes that crop management has an impact on the population genetics of T. urticae which may be related to the alternation of some acaricides under IPM. PMID- 24233156 TI - Esterases of Varroa destructor (Acari: Varroidae), parasitic mite of the honeybee. AB - Varroa destructor is an ectoparasite that causes serious damage to the population of the honeybee. Increasing resistance of the parasite to acaricides is related, among others, to metabolic adaptations of its esterases to facilitate decomposition of the chemicals used. Esterases are a large heterogeneous group of enzymes that metabolize a number of endogenous and exogenous substrates with ester binding. The aim of the present study was to determine the activity of esterases in the body extracts (BE) and excretion/secretion products (E/SP) of the mite. The enzymes contained in the E/SP should originate mainly from the salivary glands and the alimentary system and they may play a particularly important role in the first line of defence of the mite against acaricides. Activity of cholinesterases (ChEs) [acetylcholinesterase (AChE) and butyrylcholinesterase], carboxylesterases (CEs) and phosphatases [alkaline phosphatase (AP) and acid phosphatase (AcP)] was investigated. The activity of all the enzymes except AChE was higher in the E/SP than in the BE. ChEs from the BE and from the E/SP reacted differently on eserine, a ChE inhibitor. Eserine inhibited both enzymes from the BE, increased decomposition of acetylcholine, but did not influence hydrolysis of butyrylcholine by the E/SP. Activity of the CEs from the BE in relation to the esters of carboxylic acids can be presented in the following series: C10 > C12 > C14 > C8 > C2 > C4 = C16, while activity of the CEs from the E/SP was: C4 > C8 > C2 > C14 > C10 > C12 > C16. The inhibitor of CEs, triphenyl phosphate, reduced the activity of esterases C2-C8 and C14-C16; however, it acted in the opposite way to CEs C10 and C12. The activity of both phosphatases was higher in the E/SP than in the BE (AcP about twofold and AP about 2.6-fold); the activities of AP and AcP in the same material were similar. Given the role of esterases in resistance to pesticides, further studies are necessary to obtain complete biochemical characteristics of the enzymes currently present in V. destructor. PMID- 24233158 TI - Repeated visitations of spermatophores and polyandry in females of eriophyoid mites. AB - Eriophyoid females store sperm either asymmetrically in one spermatheca, or symmetrically in both spermathecae. Previous studies have suggested that species in which females store sperm asymmetrically pick up sperm from only one spermatophore, while those with symmetrical sperm storage pick up sperm from two or more spermatophores during their lifetime. The aim of this study was to examine spermatophore visitation behaviour and symmetry of sperm storage in Aculops allotrichus from the black locust tree and Cecidophyopsis hendersoni from the yucca. This would indicate monandry or polyandry in these species. In both eriophyoids, the spermatophore visitation consisted of three phases: mounting, lying on the spermatophore and dismounting. Aculops allotrichus stored sperm asymmetrically. However, nearly one-third of the observed females visited two spermatophores, rather than only one in their lives. When A. allotrichus females visited two spermatophores they spent a similar amount of time at the first and at the second visitation. Also, the times of visitation of the first of the two spermatophores and the single spermatophore in a female lifetime did not differ significantly. This would suggest that apart from monandry, double insemination also occurs in this species. By contrast, C. hendersoni females were polyandrous. They stored sperm symmetrically and visited several spermatophores, on average 1.54 (max 6) per day, and up to 33 spermatophores in their lives. The benefits of repeated spermatophore visitation and the possible mechanisms of sperm storage in both species are discussed. PMID- 24233159 TI - Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation. AB - Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-XL protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-XL protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases. PMID- 24233161 TI - FDG PET/CT in the liver: lesions mimicking malignancies. AB - PURPOSE: 18F-fluorodeoxyglucose (FDG) PET/CT is invaluable in managing liver lesions, in particular in the evaluation of suspected liver metastases. It is both sensitive and specific in detecting liver metastases from a wide range of primary cancers, and may change clinical management, most commonly by detecting additional lesions and decreasing the number of futile surgeries. However, some benign lesions may also show increased metabolic activity which can lead to false positive PET findings. We describe some of these lesions and their imaging characteristics that may help in differentiating them from malignant metastases. METHODS: e reviewed all whole body FDG PET/CT studies performed over a 5-year period in our institution, and identified those with focal liver lesions showing increased FDG uptake for which histological results were available. RESULTS: majority of lesions showing increased metabolic activity were due to malignant disease, such as metastases or primary liver tumours. However, we also found increased FDG uptake in non-neoplastic lesions such as Cryptococcosis, abscesses, and secondary inflammation from cholecystitis. Increased metabolic activity was also seen in some benign neoplasms such as hepatic adenomas and hemangioendotheliomas. CONCLUSION: DG PET/CT is currently the most sensitive non invasive imaging modality for the detection of hepatic metastases, particularly from the gastrointestinal tract. False positive results are rare, and have been described mainly in abscesses. However, other lesions can also show increased metabolic activity, and failure to differentiate these from metastases may result in inappropriate treatment. PMID- 24233160 TI - Differential responses of root growth, acid invertase activity and transcript level to copper stress in two contrasting populations of Elsholtzia haichowensis. AB - The present study aimed to test a hypothesis that acid invertases in root of metallophytes might play important roles in root growth under heavy metal stress. Plants of two contrasting populations, one from an ancient Cu mine (MP) and the other from a non-contaminated site (NMP), of metallophyte Elsholtzia haichowensis were treated with Cu in controlled experiments. The results showed that MP was Cu tolerant under 10 MUM Cu2+ treatment. Cu treatment resulted in a higher root/shoot biomass ratio in MP compared to NMP. Scaling exponent in root/shoot allometric function in MP was lower than NMP. More complicated root architecture was observed in MP under Cu stress. Four full-length cDNAs (EhNcwINV, EhCcwINV, EhNvINV and EhCvINV) encoding cell wall and vacuolar invertases were cloned. Both of the transcript level and activity of the acid invertase in MP elevated under Cu treatment. There were positive correlations between root acid invertase transcript level, activity and root/shoot biomass ratio. The results indicated important roles of acid invertase in governing root growth under Cu stress. It also suggested that there was a possible interrelation between acid invertases and Cu tolerance mechanisms in MP of E. haichowensis. PMID- 24233162 TI - Foreword. PMID- 24233163 TI - Genetic techniques for control of sexuality in fish farming. AB - Recent developments in Ministry of Agriculture, Fisheries and Food (MAFF) laboratories in the genetic control of sexuality in fish are briefly reviewed. Techniques include the development of a range of spawning times, the control of sex-ratio and the elimination of sexual maturity by induced polyploidy. PMID- 24233164 TI - The integrated development and application of controlled reproduction techniques in Pacific salmonid aquaculture. AB - During the last several years there has been rapid progress in the development and application of controlled reproduction and associated biotechnologies to the culture of salmonids. This review focuses on the development of those techniques for Pacific salmon (Oncorhynchus species) and rainbow trout (Salmo gairdneri). These include methodologies for the induction of ovulation, storage of gametes, chromosome set manipulation, i.e., induced gynogenesis and triploidy, hormonal feminization, hormonal sterilization and hormonal masculinization of genotypic females to produce milt containing only female spermatozoa.The current and future applications of these methodologies to the commercial mariculture of salmonids and to the enhancement and management of ocean and fresh water stocks are described. The implementation of each individual methodology for the control of reproduction can in itself have a significant impact on the efficiency of culture systems. It is, however, from the combination of specific complementary methods in production systems that the greatest gains will ultimately be made.It is concluded that the utilization of single or paired controlled reproduction techniques by themselves or in combination with other biotechnologies (e.g. sterilization plus growth acceleration) offer significant advantages for both the commercial mariculture of salmonids and the rearing of salmonids by government agencies for release into the oceanic or lacustrine environment. PMID- 24233165 TI - Central regulation of reproduction in teleosts. AB - As in other vertebrates, reproduction in teleosts depends upon interactions taking place along the brain-pituitary-gonads axis. At the central level, these interactions involve at least three types of factors:A gonadotrophin-releasing factor which has recently been isolated from chum salmon brain extracts. This decapeptide, whose structure is (Trp(7)-Leu(8))-LHRH, appears to have a widespread distribution among teleosts, and is less active that LHRH or LHRH analogues in releasing gonadotrophin from the teleost pituitary. Immunohistochemical and quantitative studies have demonstrated that Gn-RH neurons are mainly located in the ventral telencephalon and the preoptic area, while projections are found in the entire brain and the pituitary gland.A gonadotrophin release-inhibiting factor has been demonstrated in the anterior preoptic region of the goldfish and a large set of data suggests that dopamine has GRIF activity in goldfish, and in other teleost species, by direct action on the gonadotrophs. Accordingly, a dopaminergic preoptico-hypophyseal pathway could be demonstrated in the goldfish brain.Sex steroids exert, depending on the dosages, either a negative feedback in sexually mature fish or a positive feedback in immature fish. Such a positive feedback is caused by estrogens and aromatizable androgens. Accordingly, the brain of teleosts contains high levels of aromatase activity in particular in the telencephalon and anterior hypothalamus. The distribution of estrogens concentrating cells within the brain is consistent with possible interactions with Gn-RH or catecholaminergic neurons at the level of certain brain territories.These data are discussed in relation with the functional significance of different brain areas where interactions between these different factors possibly take place, in particular the terminal nerve, the ventral telencephalon, the preoptic area and nucleus lateralis tuberis. PMID- 24233166 TI - Photoperiodic mechanisms and rhythms of reproduction in the female rainbow trout. AB - The present work investigates the importance of circadian and circannual rhythms in the photoperiodic control of reproduction in the rainbow trout. Maintenance of groups of 20-30 female trout under continuous light (LL), constant long (18L:6D) or short (6L:18D) days and conditions of constant temperature (8.5-9.0 degrees C) and feeding rates (0.5% body weight, day(-1)), starting in February, produced markedly different spawning periodicities during the first and subsequent years of treatment. At the end of the first year, spawning was advanced by up to 2 months in the fish under LL and 18L:6D and delayed by up to 5 months in those under 6L:18D when compared with the December spawning of control fish under ambient light. Continued exposure of the fish to the same photoperiod regimes produced cycles of spawning and peak levels of testosterone, oestradiol-17beta and calcium (as an index of vitellogenin) at intervals of 150-170 days under LL and 18L:6D and 320-420 days under 6L:18D. The functional importance of these spawning cycles and their relationship to circannual rhythms and the control of reproduction is discussed.Exposure of fish to skeleton (6L:4D:2L:12D, 6L:6D:2L:10D and 6L:8D:2L:8D) and resonance (6L:42D, 6L:48D and 6L:54D) procedures produced ranges of spawning times up to two months in advance of control fish. Results with the resonance regimes, where fish received only a half the light-dark cycles and a quarter of the total daylight hours of those on ambient light cycles show that trout do not measure daylength and time by counting daily cycles or by hour-glass mechanisms. Collectively, these data support the proposition that rhythmic processes of photosensitivity are involved in the modulation of reproductive development in the rainbow trout and that circadian and circannual rhythms cooperate in the timing and entrainment of this cycle. PMID- 24233167 TI - Delayed gametogenesis and spawning of sea bass (Dicentrarchus labrax L.) kept under different photoperiod and temperature regimes. AB - The present work investigates the importance of day length and temperature in the control of reproduction of sea bass, as well as the effectiveness of LHRHa and HCG in inducing spawning out of season in this species. A controlled regime was produced and seasonal cycles with high components of temperature and photoperiod were extended from the summer solstice for at least 6 months, followed by a short photoperiod regime for 3 months before a new increase in these components. Natural spawning in the control fish occurred more frequently in mid February, although it was also observed in January and early March. Temperature manipulation delayed the spawning one month with respect to the controls, although some of the animals entered into gonadal regression. Photoperiodic manipulation delayed maturation for three months with respect to controls but it was necessary to perform hormonal induction of spawning. Although LHRHa and HCG were both applied, only intraperitoneal injections of LHRHa were effective in inducing spawning of sea bass out of season when the temperatures were 17 degrees C. Dephasing between the annual changes in photoperiod in relation to the coordination of the different events of the sexual cycle of sea bass is considered. PMID- 24233168 TI - Regulation of oocyte maturation in the rainbow trout,Salmo gairdneri: role of cyclic AMP in the mechanism of action of the maturation inducing steroid (MIS), 17alpha-hydroxy, 20beta-dihydroprogesterone. AB - In fish, oocyte maturation (resumption of meiosis after completion of vitellogenesis and before ovulation) is triggered by maturation inducing steroids (MIS) which generally appear to be secreted in the ovary in response to stimulation by a pituitary maturational gonadotropin. Converging data from different laboratories show that 17alpha-hydroxy, 20beta-dihydroprogesterone (17alpha, 20beta-OH-P) is the principal MIS in salmonoids; but clear identification remains to be done in other taxonomic groups.The experiments reported here in the rainbow troutSalmo gairdneri examine the possible involvement of oocyte cAMP on the mechanism of MIS action. The action of 17alpha, 20beta-OH-P, on germinal vesicle breakdown (GVBD) in oocytes incubatedin vitro within the follicle, was inhibited by various substances expected to elevate the intraoocyte concentrations of cAMP: cAMP (>= 1 mM) or dibutyril cAMP (>= 2 mM), phosphodiesterase inhibitors such as theophylline (>= 0.2 mM) or 3-isobutyl-1 methylxanthine (IBMX >= 0.1 mM), adenylate cyclase activators such as cholera toxin (> 100 nM) or forskolin (>= 0.03 mM). In fact, the combined action of IBMX (1 mM) and forskolin (0.01 or 0.05 mM)in vitro was to promote accumulation of intraoocyte cAMP within 1 to 5 hours. Oocyte cAMP concentrations exhibited a large variability between different females, depending on the stage of oocyte development; a significant positive correlation between oocyte cAMP concentration and the follicular weight, and a significant negative correlation between oocyte cAMP concentration and the median efficient dose of 17alpha, 20beta-OH-P for induction of GVBD, were observed. Finally, when intrafollicular oocytes were incubatedin vitro, the addition of a maturation-inducing concentration of 17alpha, 20beta-OH-P (3*10(-6)M) induced a significant decrease of oocyte cAMP within the first 10 hours of incubation. These results show that cAMP appears to play a central role in the regulation of oocyte sensitivity to 17alpha, 20beta-OH P and in the intraoocyte mechanisms leading to GVBD in trout.These data are discussed together with the few indications available in fish concerning the mechanism of MIS action which can be compared to some extent with the amphibian model. PMID- 24233169 TI - Fluctuations in gonadotropin and ovarian steroids during the annual cycle and spawning of the common carp. AB - The main objective of the paper is to describe the annual changes in hormones associated with reproduction in the female carp under the conditions prevailing in the Israeli fish culture. Fish were sampled monthly throughout 1984; gonadosomatic index (GSI) was calculated and the diameter of ovarian follicles was measured. Gonadotropin (GTH) content in the pituitary and the circulating GTH, estradiol, testosterone and 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17, 20-P) were determined by specific radioimmunoassays. GTH, estradiol and testosterone showed a bimodal annual pattern. The late summer peak was associated with initial vitellogenesis while the peak in spring occurred just before spawning, which took place in April-May. A resting phase in ovarian activity was noted in June and July. The levels of 17, 20-P were very low compared with those occurring during spawning induction. The paper summarizes a previous study by our laboratory on the changes in circulating hormones, as related to oocyte stages, in female carp induced to spawn by a GTH-calibrated pituitary extract. This study associates the short but prominent peak in 17, 20-P with the presence of follicles with maturing oocytes in the ovary. A correlation was found between the percentage of oocytes with eccentric germinal vesicle initially present in ovarian biopsies of females carp and their spawning success after hypophysation. The paper describes simple means to ensure successful induction of spawning in carp by utilizing a calibrated pituitary extract and prior selection of females that would respond to the induction treatment. PMID- 24233170 TI - Steroidogenesis in rainbow trout (Salmo gairdneri) at various preovulatory stages: changes in plasma hormone levels andin vivo andin vitro responses of the ovary to salmon gonadotropin. AB - In order to specify the timing of some changes in ovarian steroid production during the transition from vitellogenesis to ovulation, plasma hormones levels andin vivo andin vitro responses of the ovary to salmon gonadotropin (s-GtH) or dibutyryl-cyclic adenosine mono-phosphate (db-cAMP) were recorded in relationship with the state of germinal vesicle migration in the oocyte.In vivo, a small, but significant, increase of plasma 17alpha-hydroxy-20beta-dihydroprogesterone (17alpha, 20beta-OH-P) level was detected earlier (at the "subperipheral germinal vesicle" stage) than the increase of GtH level (detectable at the "peripheral germinal vesicle" stage) and the decline of oestradiol-17beta (E2-17beta) (also detectable at the "peripheral germinal vesicle" stage). Negative correlations were established between E2-17beta levels and GtH (rho=-0.53) or 17alpha,20beta OH-P (rho=-0,43) levels while a positive correlation occurred between 17alpha,20beta-OH-P and GtH levels (rho=+0,54).In vivo no action of GtH on the decline of E2-17beta levels was detected GtH did not stimulate 17alpha,20beta-OH P production, within 72h, in females at the "end of vitellogenesis" stage. It had significant effect in females at other stages closer to ovulation, but the pattern of responses changed according to the stage.In vitro db-cAMP like GtH was able to stimulate 17alpha,20beta-OH-P output from ovarian follicles. The greatest response was observed at the later stage. (GVBD). Testosterone output was also increased by GtH, but the lowest response was observed at the later stage (GVBD). Androstenedione output was lower than testosterone output.In vitro, a small but significant decline of E2-17beta output was induced by GtH. We conclude that substantial changes occur during the very last stages prior to ovulation, both in the steroidogenic potential of the ovary and in the ovarian sensitivity to GtH. 20beta-oxydoreductase is probably progressively induced during GV migration when GtH basal levels are increasing but still relatively low. Without minimizing the role of discrete pulses of GtH on this induction, we could expect synergic actions of other hormones. Thus a high testosterone/oestradiol ratio in the follicle environment favours 17alpha,20beta-OH-P secretion. PMID- 24233171 TI - Gonadal steroidogenesis and the possible role of steroid glucuronides as sex pheromones in two species of teleosts. AB - In general, female zebrafish,Brachydanio rerio, ovulate only in the presence of males. The stimulant must be pheromonal as even male holding water is capable of inducing ovulation. After ovulation the mating phase begins. During this phase the male follows the female and oviposition as well as fertilization takes place. Both the ovulation and the mating are controlled by pheromones synthesized by the gonads. Ovulation can be induced by testicular homogenates. After the lipid material has been extracted from the testicular homogenates, the remaining aqueous phase can still induce ovulation. However, when the aqueous phase is treated with the enzymebeta-glucuronidase, it loses the ability to induce ovulation. This is an indication that glucuronides, probably steroid glucuronides, are the compounds responsible.During the mating phase, ovulated female zebrafish become attractive to males. It was found that, after ovulation, ovarian extracts contain the compounds responsible for attracting males. The attractant consists of a mixture of steroid glucuronides.After incubation of the gonads with(3)H-precursors seven steroid glucuronides have been identified in the testis and five in the ovary.Under fish culture conditions the African catfish,Clarias gariepinus, can produce postivitellogenic oocytes throughout the year. However, in capitivity neither males nor females spawn. In female catfish maturation and ovulation can be induced by treatment with gonadotropins. It might be possible that, analogous to the zebrafish, some reproductive processes in the catfish have to be induced by pheromones. It has been demonstrated that pheromonal compounds released by the seminal vesicles are involved in the attraction of female conspecifics. The steroid glucuronide synthesizing capability of the testes and the seminal vesicles of the male catfish are examined, as well as that of the ovary before and after ovulation of the female catfish. Both testes and seminal vesicles appear to be capable of steroid biosynthesis but only the latter synthesizes steroid glucuronides. Six of these conjugates have been isolated and identified. In the female catfish the ovaries are capable of synthesizing seven steroid glucuronides, but only after ovulation. PMID- 24233172 TI - Effects of pimozide and LHRH-Aa on carp (Cyprinus carpio L.) oocyte maturation and ovulationin vivo. AB - Effects of pimozide (Pim) and [(D-Ala(6), Pro(9)-NEt) LHRH] (LRH-Aa) on common carp oocytes maturation and ovulationin vivo under laboratory and commercial fisheries farm conditions were investigated.Although injections of Pim and LRH-Aa at the doses of 10 mg and 50 ug/kg body weight respectively, did not increase mGtH levels (66.7-155.8 mg/ml) as much as injections of carp pituitary extract (chh) (382.1 ng/ml), induced GtH levels were high enough to induce ovulation. Changes in the ovary caused by Pim and LRH-Aa were similar to those induced by chh, and Pim injected together with LRH-Aa in a single injection gave the same results concerning ovulation induction as when they were applied separately at 6h interval. PMID- 24233173 TI - Biology of the gametes of some teleost species. AB - Our knowledge of the biology of fish gametes is still limited. Up to now research was short-term, aiming at solving practical questions connected with gamete storage and artificial insemination. More information on gamete biology is now available and has been summarized in this minireview.In vivo storage of gametes in the genital tract after ovulation or spermiation may be influenced by the osmotic environmentvia changes in the ionic composition of the companion fluid. There is great inter-individual variability in gamete survival bothin vivo andin vitro. Mechanisms involved in the initiation of trout sperm motility have been analysed; after dilution in water or NaCl solution (125 mM) at pH > 7, Ca(++) entry due to changes in membrane potential have been observed. The involvement of cAMP and protein phosphorylation has been reported. The morphological, physical and biochemical changes in eggs that have been studied after fertilization and the corticol reaction lead to a better understanding of the mechanisms of polyspermy blockage. PMID- 24233174 TI - Interaction "nutrition-reproduction" in fish. AB - In wild fish, gonad maturation and spawning induce modifications in feeding behaviour and dynamics of body stores which are possibly responsible for metabolic disorders. Conversely, food manipulations can modify reproduction of captive female broodstock. A restricted diet during early stages of the life cycle delays the first maturation age, a quantitatively restricted food supply during the stages of oocyte differentiation reduces the egg number, while a reduction of food levels during the last phases of oogenesis has only a small effect on egg size, composition and hatchability. During the spawning period, salmonid female broodstock seem to be more able to utilize carbohydrates than immature fish, they valorize the energy brought in by fats and have low quantitative requirements for proteins (28%). On the other hand, Red Sea bream broodstock have higher needs for proteins (45%).The incorporation into diet of liposoluble vitamins and essential fatty acids is necessary for normal reproduction, but (n-6) fatty acids seem to play a more important role than in juveniles. Although the effects and physiological role of carotenoids are not yet well known in salmonids, they are necessary for normal development in Red Sea bream. Although little work has been done on the effects of mineral nutrition, special attention must be paid to trace elements, manganese in particular.The major part of this review concerns female broodstock, since very little interest has been devoted to males. PMID- 24233175 TI - Environmental effects on feed utilization. AB - Both external and internal factors affect the response of fish to variations in dietary quantity and quality. An attempt is made to review major, recent studies on the series of intermediate steps (intake, digestion, metabolism, excretion and retention) involved in the global response of fish to environmental changes. Among these external factors, greater attention is however devoted to those that are the most important natural effectors within the aquatic environment: temperature, ambient oxygen and salinity. The changes brought about by a change in temperature at different levels of nutrient utilization have been studied to a great extent in the recent past. As temperature affects in the first instance, the voluntary food intake, a discussion on current nutrient requirement data should preferably be dealt with in absolute terms. While critical levels of oxygen below which growth is hindered are sufficiently defined for many species, precise data on the direct effects of oxygen deficiency on nutrient utilization are still fragmentory. With regard to salinity, a distinction between stenohaline and euryhaline species and a knowledge of the physiological mechanisms corresponding to their life cycles are required before attempting comparative analyses. Within euryhaline species, best performances are noted at salinities isotonic to the internal medium. Despite accumulating evidence on the effects of cyclical phenomena, the chronobiological approach to fish culture remains practically unexplored. PMID- 24233176 TI - Nutrition, hormones and growth. AB - A review is presented relating to the effects of hormones on food intake and nutritional state and also of the effects of food intake and nutritional state on hormone activity. These interactions and their effect on fish growth are described.Growth hormone, thyroid hormones, insulin, and gonadal steroids have all been implicated in the normal growth processes of fish and their metabolic actions have been related to the nutritional state of the animal. Furthermore, variations in plasma levels and hormone application appear to affect food intake and food conversion.Anabolic steroids and their possible involvement in aquaculture practice has been an area of active investigation for the past few years. The current situation is reviewed, particularly regarding relevance to protein intake. PMID- 24233177 TI - Utilization of ascorbate-2-sulfate in fish. AB - Although most vertebrate animals synthesize L-ascorbic acid (C1), some animal species lack the ability to produce L-gulonolactone oxidase and are thus dependent upon a dietary source of vitamin C. Fish are unique among this latter group in that they store a chemically stable form of vitamin C and appear to metabolize this compound differently from other vitamin C-requiring organisms. Ascorbate-2-sulfate (C2) contributes to total body stores of ascorbate, but the commonly used assays for ascorbate concentrations in tissues and body fluids do not generally measure C2. An HPLC assay distinguishes between and measures both C1 and C2. Modification of the less exact but commonly used DNPH method can provide adequate data to estimate total vitamers C, C1, and (by difference) C2. Since vitamin C is a required component of feed for salmonids, catfish, eels, shrimp and carp, use of C2 in feed formulation would provide a bioavailable form of ascorbate which is heat and water stable at pH 4-13. PMID- 24233178 TI - Dietary requirements of rainbow trout for tryptophan, lysine and arginine determined by growth and biochemical measurements. AB - Three separate studies were performed to determine the dietary requirements of rainbow troutSalmo gairdneri for tryptophan (Trp), lysine (Lys) and arginine (Arg) from both growth and biochemical data. The growth studies were carried out over a 12 week period. From graphical plots of % mean weight gain against % amino acid in diet the following requirement values were obtained, Trp 0.25% diet (0.4% dietary crude protein); Lys 1.9% diet (4.3% dietary protein); and Arg 1.6-1.8% diet (3.6-4% dietary protein). Plasma and liver amino acid concentrations measured 20h after feeding did not prove useful for determination of requirement values. Hepatic activities of Trp pyrrolase (TP), Lys alpha ketoglutarate reductase (LKGR) and arginase were not significantly affected by varying levels of Trp, Lys and Arg respectively in the diet. TP has a cytosolic location and a Km of 0.2 mM for Trp; LKGR is mitochondrial and the Km for Lys is 7.3 mM; arginase is also mitochondrial and has a Km of 4.9 mM for arginine. Measurements of expired(14)CO2, after injection of a tracer dose of(14)C amino acid, did allow estimates of requirement levels to be made. The values obtained from the oxidation studies reinforced the values obtained from the growth data but were not precise enough to justify using this method on its own. PMID- 24233179 TI - The role of nutritional factors in the prevention of peroxidative damage to tissues. AB - The multi-level defence system present in vertebrate cells to protect against chain reactions initiated by free radicals (mainly toxic metabolites of oxygen) is outlined. It comprises superoxide dismutases (Cu-Zn and Mn dependent), glutathione peroxidase (Se dependent), vitamin E and glutathione S transferase.The protective role of superoxide dismutase (SOD) was demonstrated by studies on trout (Salmo gairdneri) retina (Desrochers and Hoffert 1983). This tissue is subject to very high O2 tensions but has a high resistance to O2 toxicity that is dependent on a high dismutating capacity. The activities of both the cytosolic Cu-Zn SOD and the mitochondrial Mn SOD in the liver of rainbow trout were significantly altered in response to changes in dietary intake of these minerals.Deficiency of Se did not affect the growth rate of rainbow trout but led to greatly reduced activities of hepatic and plasma glutathione (GSH) peroxidase. There was no evidence of a Se-independent GSH peroxidase activity. In rainbow trout depleted of Se there was a compensatory increase in hepatic GSH S transferase activity. This enzyme in conjunction with GSH has been shown to inhibit lipid peroxidation in the Festimulated microsomal systemin vitro. A dietary synergism between vitamin E and Se in rainbow trout has been demonstrated.The vitamin E requirement of rainbow trout is related to the polyunsaturated fatty acid (PUFA) content of the diet. The molar ratio PUFA: vitamin E in rainbow trout tissues is lower than that in rats. Time course studies on the uptake of orally administered vitamin E showed rapid incorporation into biomembranes; few differences between normal and vitamin E deficient fish were evident. The ester form of vitamin E was more slowly assimilated than the alcohol. PMID- 24233180 TI - Cardiovascular, respiratory, and blood adjustments to hypoxia in the Japanese eel,Anguilla japonica. AB - The cardioventilatory performance of the Japanese eel,Anguilla japonica, was evaluated during acute exposure to hypoxia. The eel became an oxygen conformer as ambient PO2 fell below the critical value of 110 mmHg. Although arterial and venous PO2 also fell progressively, the arterial O2 content remained constant down to an ambient PO2 of about 60 mmHg. Arterial blood O2 saturation was maintained at 85% even at 40 mmHg. The increase in the supply of O2 to the animal during hypoxia was due to a combination of adaptive adjustments: (1) an increase in ventilation: perfusion ratio brought about mainly be bradycardia; (2) an increase in respiratory exchange surface area which was manifested as an increase in branchial blood transit time and quantified as a rise in transfer factor, water-blood overlap coefficient and utilization (%); (3) an increase in blood O2 affinity and capacitance coefficient as a result of respiratory alkalosis and Bohr-Root shift and a decrease in haemoglobin allosteric modulator (GTP, ATP) concentrations in the RBC. These factors together helped to increase the efficiency of O2 transfer across the gills. PMID- 24233181 TI - Postoperative fever specific to neuroendoscopic procedures. AB - The most common complication of neuroendoscopic surgery is postoperative fever without infection, although the details have not been discussed. The objective of this study was to clarify the clinical features and predicting factors of the postoperative fever following neuroendoscopic procedures. Between March 1998 and March 2013, 83 patients (46 males, 37 females; median age, 14.0 years) who had undergone surgery via the transventricular approach under a neuroendoscopic view were included in this study. A total of 86 neuroendoscopic procedures were performed in 83 patients. The incidence and duration of postoperative fever (>=38.0 and >=39.0 degrees C) over the 7 days after surgery were examined. Moreover, the following variables predictive of fever were investigated: age, sex, neuroendoscopic procedure, operative time, and intraoperative irrigation fluid. The incidence of postoperative fever was 65.1 % (>=38.0 degrees C) and 15.1 % (>=39.0 degrees C). The median level of the highest fever was 38.6 degrees C. The fevers developed immediately after surgery and spontaneously disappeared within four postoperative days. Only age was related to postoperative fever (p = 0.032). The postoperative body temperature was negatively correlated with age in all 86 surgeries (p < 0.001, Spearman r = -0.396). In particular, patients under 10 years of age tended to have postoperative fever (p = 0.005). The result of this study demonstrated a peculiar pattern of fever following neuroendoscopic procedures. This type of fever did not cause serious problems; however, special attention should be paid to the high incidence of postoperative fever in patients under 10 years of age. PMID- 24233182 TI - Trends in anxiolytic-hypnotic use and polypharmacy in Taiwan, 2002-2009: a nationwide, population-based survey. AB - OBJECTIVES: Use of anxiolytics-hypnotics, including benzodiazepines and "z" hypnotics, is a public health concern. This study aimed to investigate the trends in prevalence of anxiolytic-hypnotic drug use and polypharmacy (simultaneous use of two or more anxiolytics-hypnotics) in Taiwan. METHODS: A dynamic sample of one million individuals who were randomly selected from the National Health Insurance database was used to detect populationwide trends in the use of anxiolytics hypnotics in Taiwan between 2002 and 2009. The analyses included drugs that are administered orally, intravenously, or intramuscularly as well as single or compound drugs. The authors identified the number of individuals who used the drugs, the sum of days of reported drug use for all individuals (person-days), and the distribution of anxiolytic-hypnotic polypharmacy for all claims for ambulatory, pharmacy, and hospital care. RESULTS: Annual prevalence of any anxiolytic-hypnotic use in Taiwan was higher than 20%. The number of person-days greatly increased from 2002 (4.0%) to 2009 (6.6%). The increases in use between 2002 and 2009 were greatest for clonazepam (prevalence, 7% versus 1.8%; person days, .2% versus .6%) and zolpidem (prevalence, 2.4% versus 4.2%; person-days, .5% versus 1.5%). Polypharmacy accounted for almost 70% of all person-days of anxiolytic-hypnotic use. CONCLUSIONS: This nationwide, population-based survey presents real-world epidemiological evidence about anxiolytic-hypnotic use. The adverse effects of the long-term use of anxiolytics-hypnotics have been established, and unnecessary use of these drugs, particularly in polypharmacy regimens, should be avoided. PMID- 24233183 TI - The influence of different radiopacifying agents on the radiopacity, compressive strength, setting time, and porosity of Portland cement. AB - OBJECTIVES: The aims of this study were to evaluate the radiopacity, compressive strength, setting time, and porosity of white Portland cement (PC) with the addition of bismuth oxide (Bi2O3), zirconium dioxide (ZrO2), and ytterbium trifluoride (YbF3) after immersion at 37 degrees C for 7 days in distilled water or phosphate buffer saline. MATERIALS AND METHODS: Specimens measuring 8 mm in diameter and 1 mm in thickness were fabricated from PC with the addition of 10, 20, and 30 wt% Bi2O3, ZrO2 or YbF3. ProRoot MTA (Dentsply, Tulsa, OK, USA) and pure PC were used as controls. For radiopacity assessments, specimens were radiographed alongside a tooth slices and an aluminum stepwedge on Extraspeed occlusal dental films (Insight Kodak, Rochester, New York). Mean optical density of each specimen was calculated and used to express radiopacity of the material as an equivalent thickness of aluminum. Compressive strength was measured by using 4-mm diameter and 6-mm high specimens and Universal testing machine. High pressure mercury intrusion porosimeter (Carlo Erba Porosimeter 2000) was employed to measure the porosity of the specimens. The setting time was measured by using a needle of 100 g in weight. The morphology of specimens was evaluated using a scanning electron microscope (TESCAN Mira3 XMU, USA Inc.). Data were analyzed by one-way ANOVA and post hoc Tukey test (P < 0.05). RESULTS: The PC with the addition of at least 10 wt% Bi2O3 and 20 wt% ZrO2 or YbF3 demonstrated greater radiopacity value than the recommended 3 mmAl cut-off. ZrO2 and YbF3 increased the compressive strength of PC, but it was not statistically significant (P > 0.05), while Bi2O3 decreased it (P < 0.05). All radiopacifiers significantly increased the porosity of the experimental cements (P < 0.05). Bi2O3 extended the setting time of PC (P < 0.05), whilst ZrO2 and YbF3 did not significantly affect it (P > 0.05). CONCLUSIONS: ZrO2 and YbF3 may be used as a suitable alternative to replace Bi2O3 in MTA without influencing its physical properties. PMID- 24233184 TI - Primary human chorionic gonadotropin secreting germinoma of the corpus callosum. AB - BACKGROUND: Primary intracranial germinomas are a rare subset of intracranial tumors derived from mis-incorporated germ cells within the folding neural plate during embryogenesis. Though known to arise from midline structures in the central nervous system (CNS), occurrence within the corpus callosum is exceedingly rare. CASE DESCRIPTION: We present a rare case of secreting primary intracranial germinoma with extensive intraventricular metastasis presenting as a multi-cystic butterfly lesion in the genu of the corpus callosum in a young boy. CONCLUSION: Intracranial germ cell tumors must be considered for any multi-cystic lesion arising from midline structures in the CNS in the preadult population. PMID- 24233185 TI - Kinetic isotope effect in malonaldehyde determined from path integral Monte Carlo simulations. AB - The primary H/D kinetic isotope effect on the intramolecular proton transfer in malonaldehyde is determined from quantum instanton path integral Monte Carlo simulations on a fully dimensional and validated potential energy surface for temperatures between 250 and 1500 K. Our calculations, based on thermodynamic integration with respect to the mass of the transferring particle, are significantly accelerated by the direct evaluation of the kinetic isotope effect instead of computing it as a ratio of two rate constants. At room temperature, the KIE from the present simulations is 5.2 +/- 0.4. The KIE is found to vary considerably as a function of temperature and the low-T behaviour is dominated by the fact that the free energy derivative in the reactant state increases more rapidly than in the transition state. Detailed analysis of the various contributions to the quantum rate constant together with estimates for rates from conventional transition state theory and from periodic orbit theory suggest that the KIE in malonaldehyde is dominated by zero point energy effects and that tunneling plays a minor role at room temperature. PMID- 24233186 TI - Dream it, design it, print it in 3-D: what can 3-D printing do for you? AB - So maybe we are not all driving to work in a flying car or are being beamed up by a transporter yet, but we should be clearing out a space in the lab and perhaps in the office for a replicator. Sure, they may not work the same as the replicators on Star Trek that instantaneously pop out hot, full-course meals to suit any crew member's whim, but they can generate three-dimensional (3-D) objects to match your computer design. PMID- 24233187 TI - Adding value in additive manufacturing: researchers in the United Kingdom and Europe look to 3D printing for customization. AB - Having already made a big impact in the medical sector, three-dimensional (3-D) printing technology continues to push the boundaries of cost efficiency, convenience, and customization. It has transformed some aspects of medical device production. However, expectations of the technology are often exaggerated in the media, so we spoke to leading researchers in the field about its practical applications and what can be expected in the near future. PMID- 24233188 TI - The body printed. AB - It takes only a few minutes for the NovoGen MMX to print out a chunk of human liver cells. It?s a small chunk, only 4-mm wide and 20 cell layers thick, which wouldn't do much good in a human patient. But at a cellular level, this tiny swatch of machine-made flesh has all the essential ingredients of an original organ: tight hexagons of hepatocytes and fatty stellate cells and endothelial cells gathered into nascent capillaries. It produces cholesterol, albumin, and detoxifying P450 enzymes. After it is printed, the ensemble can survive for almost an entire week?nearly triple the endurance of classic two-dimensional (2 D) liver cultures. PMID- 24233189 TI - Moving the science of behavioral change into the 21st century: part 2. AB - What follows is the second part of a two-part special series of articles that illustrate through examples the breadth and depth of the field of behavioral change science and highlight the challenges in moving it in to the 21st century. The first part appeared in the September/October issue of IEEE Pulse (see [1] [3]). PMID- 24233190 TI - Healthy apps: mobile devices for continuous monitoring and intervention. AB - It is now known that nearly half of the toll that illness takes in developed countries is linked to four unhealthy behaviors: smoking, excess alcohol intake, poor diet, and physical inactivity. These common risk behaviors cause preventable, delayed illness that then manifests as chronic disease, requiring extended medical care with associated financial costs. Chronic disease already accounts for 75% of U.S. health-care costs, foreshadowing an unsustainable financial burden for the aging population [1]. We are facing an urgent need to re engineer health systems to improve public health through behavior change, and technology-supported behavioral change interventions will be a part of 21st century health care. As new technical capabilities to observe behavior continuously in context make it possible to tailor interventions in real time, the way we understand and try to influence behavior will change fundamentally. PMID- 24233191 TI - Systems modeling of behavior change: two illustrations from optimized interventions for improved health outcomes. AB - Systems science techniques are becoming increasingly important as tools for modeling behavior change and as enablers for delivering more effective tailored interventions [1], [2]. Systems approaches offer a fresh perspective on the understanding of behavior change, providing a means for better capturing complexity, exposing gaps in the existing body of knowledge, enhancing the predictive capability of models, and ultimately enabling optimal decision making in behavioral intervention settings. PMID- 24233192 TI - The researcher and the consultant: a dialogue on null hypothesis significance testing. AB - Since its introduction, null hypothesis significance testing (NHST) has caused much debate. Many publications on common misunderstandings have appeared. Despite the many cautions, NHST remains one of the most prevalent, misused and abused statistical procedures in the biomedical literature. This article is directed at practicing researchers with limited statistical background who are driven by subject matter questions and have empirical data to be analyzed. We use a dialogue as in ancient Greek literature for didactic purposes. We illustrate several, though only a few, irritations that can come up when a researcher with minimal statistical background but a good sense of what she wants her study to do, and of what she wants to do with her study, asks for consultation by a statistician. We provide insights into the meaning of several concepts including null and alternative hypothesis, one- and two-sided null hypotheses, statistical models, test statistic, rejection and acceptance regions, type I and II error, p value, and the frequentist' concept of endless study repetitions. PMID- 24233193 TI - Assessment of toxicity and potential risk of butene-fipronil using Drosophila melanogaster, in comparison to nine conventional insecticides. AB - The toxicities of butene-fipronil to Drosophila melanogaster were evaluated, in comparison to nine conventional insecticides. According to the mean LD50 values of the larvae from CS, w(1118) and Oregan strains, butene-fipronil,abamectin, spinosad and chlorpyrifos exhibited high levels of toxicity. Imidacloprid, alpha cypermethrin and clothianidin showed middle levels of toxicity. And acephate,methomyl and acetamiprid had low levels of toxicity. To the adults, butene-fipronil, alpha-cypermethrin, spinosad, and chlorpyrifos were relatively more toxic, whereas acephate,methomyl, acetamiprid, imidacloprid, clothianidin and abamectin were relatively less toxic. Butene-fipronil and abamectin were more toxic to larvae. In contrast, spinosad,a-cypermethrin, and clothianidin were more toxic to adults.Moreover, the toxic risk assessment using a risk quotient value revealed that butene-fipronil was safe to D. melanogaster adults. Thus, our results suggested that butene-fipronil is harmful to D. melanogaster larvae, but it is relatively safe to the adults. PMID- 24233194 TI - [Effect of fluoride on the expression of endoplasmic reticulum chaperone in ameloblast of rat incisor]. AB - PURPOSE: To investigate the effect of different concentrations of fluoride on the expression of endoplasmic reticulum chaperone, and to explore the mechanism of dental fluorosis in rat. METHODS: Thirty Wistar rats were randomly divided into 3 groups. Immunohistochemistry was used to detect the expression of CRT, GRP78, XBP 1 and caspase-12 in rat incisors. Metamorph microscope images analysis system and SPSS 13.0 software package was used to analyze the data. RESULTS: Typical features of dental fluorosis were found in the fluoride group. Results of immunohistochemistry showed that CRT (F=238.6, P<0.05), GRP78 (F=27.42, P<0.05), XBP-1 (F=139.7, P<0.05) and caspase-12 (F=43.91, P<0.05) were significantly different among the 3 groups. CONCLUSIONS: Excessive fluoride can increase the secretion of CRT, GRP78, XBP-1 and caspase-12 suggest the ameloblasts and in status of endoplasmic reticulum stress and caspase-12 plays an important role during ameloblast apoptosis. Supported by National Natural Science Foundation of China (81072245) and Natural Science Foundation of Liaoning Province (20102278). PMID- 24233195 TI - [Detection and the immune status of regulatory T cells in experimental periodontitis]. AB - PURPOSE: To establish animal model in mice with orally infected periodontitis with Porphyromonas gingivalis and intraperitoneal injection of P.g antigen, simulate periodontal pathogens of human periodontal disease, and analyze the expression of regulatory T cells in this model. METHODS: The extent of periodontal bone resorption was measured by entity microscope, and inflammatory cell infiltration of the periodontal tissue lesions was observed by HE staining. Flow cytometric analysis was used to detect the expression of regulatory T cells in periodontal disease during the chronic inflammation. The expression levels of TGF-beta1, IL-10mRNA in periodontal tissue were detected by real-time quantitative PCR. SPSS 17.0 software package was used for statistical analysis. RESULTS: After 4 weeks, compared with the normal control group, the distance between cemento-enamel junction and the alveolar crest was significantly increased in periodontal disease group(P<0.05); Massive inflammatory cells were infiltrated and periodontal pockets deepened in periodontal tissue. The expression levels of TGF-beta1 and IL-10mRNA were significantly decreased (P<0.01). The ratio and numbers of Treg cells were significantly reduced in the spleen (P<0.05). CONCLUSIONS: In experimental periodontitis, the number and the function of regulatory T cells are abnormal. It may be relevant to the reduction of immune suppression cytokines. Supported by Higher Institute School Special Research Fund for Doctorate Program (20112104110013) and Science and Technology Project of Liaoning Province (2012225015). PMID- 24233197 TI - [A three-dimensional finite element study on the reaction of different force values generated from maxillary protraction appliance]. AB - PURPOSE: To analyse the stress distribution of temporomandibular joint(TMJ) and jaw and the displacement changes of each part from the reaction force generated from maxillary protraction appliance by establishing a craniomaxillofacial three dimensional finite element model (3-D FEM). METHODS: A 3-D FEM of craniofacial structure including TMJ and jaw was established from a male healthy subject by using CT scan and Mimics, Magics, MSC and other data analysis softwares. It was based on the linear elastic materials which were continuous, homogeneous, and isotropic. Then the simulation model in craniofacial 3D structure model of maxillary protraction device was establish based on the reaction principle, and different forces from 3 N to 6 N with a 37degrees centigrade angle from the occlusal plane was loaded at the bottom of the lower jaw in order to measure and analyze changes of stress and displacement in TMJ and jaw with the finite element analysis software ANSYS10.0. RESULTS: At the same angle , the stress in articular fossa and the head and neck of condyle increased with the applied force. Maximum stress was located where the stress was loaded on the mandible and the rigid fixation of maxilla. Meanwhile, this model appeared slight variation of displacement which increased with loading force. The maxillary displacement from basis cranii and occlusal plane to the parietal decreased gradually. Moreover, the mandibular displacement from the front to the rear was gradually reduced, and clockwise rotation was appeared. CONCLUSIONS: The results indicate that maxillary protraction appliance has reaction force on TMJ and jaw. With increasing of loading forces, reaction forces and deformation increase. At the same time, chin deformation may occur and the mandible has clockwise rotation. Supported by Natural Science Foundation of Shandong Province(ZR2011HM036), Medical Health and Technology Development Project(2011QZ023) of Shandong Province and Independent Innovation Project of Jinan College Institute(201202032). PMID- 24233196 TI - [Expression of Smad4 and Smad7 of BMP signaling pathway in oral squamous cell carcinoma]. AB - PURPOSE: To observe the changes of the expressions of Smad4 and Smad7 in oral squamous cell carcinoma and adjacent normal tissue, and to investigate the effects of Smad4 and Smad7 on occurrence and development of oral squamous cell carcinoma (OSCC). METHODS: Seventy-two cases with OSCC which were pathologically confirmed were included in the study. Cancer tissue and adjacent normal tissue were taken to make slices. SP immunohistochemical method was used to detect the expression of Smad4 and Smad7 in oral squamous cell carcinoma and adjacent normal tissue. SPSS11.5 software package was used for statistical analysis. RESULTS: The positive expression rate of Smad4 protein was 69.44% in adjacent normal tissues, and it was 45.83% in oral squamous cell carcinoma(P<0.05). The positive expression rate of Smad4 was lower when the degree of differentiation decreased; The positive expression rate of Smad4 with lymph node metastasis was 22.50%, while it was 65.63% without lymph node metastasis(P<0.05). The positive expression rate of Smad7 protein in adjacent normal tissues was 19.44%, and it was 83.33% (P<0.05) in oral squamous cell carcinoma, the positive expression rate of Smad7 was higher when the degree of differentiation decreased. The positive expression rate of Smad7 with lymph node metastasis was 92.50%, while it was 68.75%(P<0.05) without lymph node metastasis. CONCLUSIONS: The expression of Smad4 is significantly reduced in cancer tissues and the expression is lower when the degree of differentiation decreased; the expression rate of Smad4 with lymph node metastasis is lower compared with those without lymph node metastasis. Smad7 has the opposite effect. Loss of expression of Smad4 may contribute to the development and metastasis of oral squamous cell carcinoma. Over-expression of Smad7 may promote the development and metastasis of oral squamous cell carcinoma. The inhibition of BMP/Smads signaling pathway may result in the occurrence and development of oral squamous cell carcinoma continually. Supported by Science and Technology Development Plan (2010GSF10239) of Shandong Province and Science and Technology Special Project of Shandong Province (2012G0021852). PMID- 24233198 TI - [Relationship between ureolytic activity expression of Streptococcus salivarius urease genes ureIABCEFGD in Escherichia coli and nickel ions]. AB - PURPOSE: To obtain the clone of Streptococcus salivarius 57.I urease genes ureIABCEFGD and investigate the relationship between ureolytic activity expression of this clone in Escherichia coli and nickel ions. METHODS: The target gene was cloned by polymerase chain reaction in 2 parts separately. Then, 2 plasmids were digested by specific restriction enzymes and ligated together. The obtained plasmids were subjected to nucleotide sequence analysis and transformed into E.coli TG-1. The recombinant E.coli was added without or with different level of NiCl2. The amount of ammonia generated by ureolytic activity of each sample was measured by Nessler's assay. SPSS 17.0 software package was used for correlation analysis. RESULTS: The clone of urease genes ureIABCEFGD was proved by sequence analysis and BLAST search. The amount of ammonia generated by the recombinant strain had a positive correlation with the level of NiCl2(r=0.9714,P<0.01). When the level of NiCl2 was 50 MUmol/L, the amount of ammonia reached maximum and would have little variance despite the increase of NiCl2 level. CONCLUSIONS: Ureolytic activity expression of ureIABCEFGD has a positive correlation with the level of added NiCl2 not exceeding 50 MUmol/L. The present clone can be used to further investigate the regulation of the ureolytic activity expression of Streptococcus salivarius urease gene. Supported by Natural Science Foundation of Shanghai Municipality(08ZR1416800) and Research Fund of Science and Technology Committee of Shanghai Municipality(11411950900). PMID- 24233199 TI - [The effect of H2O2 surface treatment of posts on the bond strength between glass fiber posts and the resin cement]. AB - PURPOSE: To evaluate the effect of H2O2 on the push-out bond strength between glass fiber posts and the resin cement. METHODS: Eighteen Tenax glass fiber posts and 18 Macthpost glass fiber posts were randomly assigned to 6 groups according to the surface treatments. Group A, no surface treatment (control group); Group B, treated with silane agent; Group C, treated with 3% H2O2, then with silane agent; Group D, treated with10% H2O2, then with silane agent; Group E, treated with20% H2O2, then with silane agent; Group F, treated with 30% H2O2, then with silane agent. The posts were adhered using the resin cement to form cylindrical resin block. Each resin block was sectioned to 7 sections of 1 mm thick. A push out test was performed on other sections of each post to measure bond strengths. The date was recorded and analyzed with SPSS13.0 software package. The failure modes were examined with stereomicroscope. RESULTS: The bond strengths of Tenax post from A1 to F1 were (22.35+/-3.43) MPa, (22.75+/-1.92) MPa, (27.21+/-3.60) MPa, (32.32+/-2.19) MPa, (36.15+/-2.32) MPa and (40.51+/-2.37) MPa, respectively. The bond strengths of Macthpost post from A2 to F2 were (17.29+/-3.23) MPa, (17.01+/-3.18) MPa, (20.48+/-2.11) MPa, (23.60+/-2.60) MPa, (27.65+/-3.77) MPa and (30.52+/-2.99) MPa, respectively. No significantly difference (P>0.05) was found between Group A and Group B, except other groups. CONCLUSIONS: Treatment with H2O2 followed with silane agent can significantly improve the bond strength between Tenax and Macthpost glass fiber posts and resin cement. The group treated with 30% H2O2 has the highest bond strength, and the treatment procedure is more useful to improve the adhesion of the glass fiber post. Supported by Science and Technology Plan Project of Department of Health of Jiangxi Province (20131084). PMID- 24233200 TI - [Influence of light irradiation mode on microhardness of dual cured resin cements]. AB - PURPOSE: To investigate the influence of different light irradiation modes on microhardness of dual-curing resin cements. METHODS: The cylindrical specimens (1 mm in thickness and 7.5 mm in diameter) of 5 self-adhesive resin cements (Biscem, Clearfil SA Cement, G-CEM LinkAce, Maxcem Elite and RelyX U100) and 2 universal resin cements(DUOLINK and Nexus 3) were irradiated respectively by a continuous mode (light-curing for 20 s) and a delayed mode (light-curing 5 s + auto-curing 60 s + light-curing 20 s), and then they were placed dry in a light-proof thermostat at 37 degrees centigrade. Surface microhardness of specimen was detected at 0.5, 24 h and 4 weeks post-irradiation. After that period of time, all specimens were soaked in ethanol for 24 h, their hardness were detected again, and the percentage of hardness reduction after soaking were calculated. Data were analyzed by SPSS 16.0 software package. RESULTS: The hardness of all resin cements under both irradiation modes increased mainly within 24 h post irradiation. The irradiation mode did not affect the hardness of all resin cements 4 weeks after irradiation significantly (P>0.05), except for Biscem. However, after ethanol softening, 5 self-adhesive resin cements cured by the continuous mode had higher hardness reduction percentage than that cured by delayed mode (P<0.05); while hardness reduction percentage of 2 universal resin cements had no significant difference between continuous and delayed cure modes (P>0.05). CONCLUSIONS: The self-adhesive resin cements cured by delayed mode had better anti-softening ability. Supported by Nanjing Medical Science and Technology Development Fund (ZKX09035), Nanjing Science and Technology Development Fund (201001083) and Nanjing Medical Science and Technology Development Fund (YKK10125). PMID- 24233201 TI - [The effect of vascular endothelial cells on the proliferation of periodontal ligament cells and gingival fibroblasts]. AB - PURPOSE: To investigate the effect of vascular endothelial cells on the proliferation of periodontal ligament cells and gingival fibroblasts through a model mimicking the periodontal wound healing and regeneration. METHODS: Human vascular endothelial cells, periodontal ligament cells and gingival fibroblasts were co-cultured using a Transwell system. The number of each type of cells at 2, 4, 6, 8 and 10 days after co-culture were counted using a cell counter machine, while periodontal ligament cells and gingival fibroblasts single culture were used as control. The results were statistically processed with SPSS 13.0 software package. RESULTS: When vascular endothelial cell was present, the proliferation of periodontal ligament cells and gingival fibroblasts were faster than each single culture, the difference between them was significant (P<0.01). The proliferation of periodontal ligament cells was faster than gingival fibroblast as they were co-cultured with vascular endothelial cells(which happened at day 6), although the results were contrary when they were single cultured, the difference between them was significant (P<0.01). CONCLUSIONS: The presence of vascular endothelial cells can promote the proliferation of periodontal cells, and the effect is more prominent on human periodontal ligament cells than on gingival fibroblasts. PMID- 24233202 TI - [Effect of insulin on peroxiredoxin-6 in the osteogenic differentiation of rat's mandiular bone marrow stromal cells in high glucose]. AB - PURPOSE: To explore the effect of insulin on the expression of peroxiredoxin-6 in osteogenic differentiation of rat's mandibular bone marrow stromal cells(rBMSCs) in high glucose. METHODS: Bone marrow stromal cells were obtained from the mandible of Wistar rats and stimulated in three glucose concentrations mineral medium(5.5 mmol/L, 25 mmol/L and 45 mmol/L) with or without insulin(10-5mol/L) for 1, 3, 7, 14, and 21 days. The expression of prohibitin was quantified via enzyme-linked immuno sorbent assays (ELISA). The mineralization nodules were assessed at day 21 by alizarine red staining. Statistical analysis was performed using SPSS 15.0 soft ware package. RESULTS: High glucose of 45 mmol/L inhibited mineralization of rBMSCs and insulin can improve the mineralization in high glucose. The expression of peroxiredoxin-6 in 45 mmol/L group decreased significantly compared with 5.5 mmol/L group and 25 mmol/L group. The expression of peroxiredoxin-6 in each group achieved maximum at day 21. Insulin (10-5 mol/L) increased the expression of peroxiredoxin-6 in 25 mmol/L group and 45 mmol/L group in osteogenic differentiation of rBMSCs. CONCLUSIONS: High glucose inhibits the expression of peroxiredoxin-6 in osteogenic differentiation of rBMSCs, while insulin upregulates the expression of peroxiredoxin-6 in rBMSCs. Peroxiredoxin-6 may play an important part in later stage in osteogenic differentiation of rBMSCs. PMID- 24233203 TI - [Defects in 2061 discarded ProTaper handfiles after clinical use]. AB - PURPOSE: To explore the mechanism of failure of ProTaper NiTi handfiles during root canal preparation. METHODS: A total of 2061 discarded ProTaper handfiles were collected after clinical use. The files were studied under stero-microscope to determine the type of defect. The fractured files were photographed digitally and the pictures were analyzed by software Image-Pro Plus to measure the distance from the break point to the tip. The data were statistically analyzed by using SPSS 11.0 software package. RESULTS: Plastic deformation was observed in 166 files (8.2%), and the types of defects included unwinding, winding flutes, and plastic bending. Instrument separation occurred in 581 files (28.2%), and the fracture rate was the highest in the F2 file group (41.7%). The SX file group had the highest facture level, and the mean distance from the breakpoint to the file tip was (4.4+/-1.1) mm. CONCLUSIONS: For shaping files, especially at the apical level, the main cause of mental failure is overload of torque, whereas for finishing files, especially at the higher level, is cycle fatigue. Understanding the defect types of ProTaper handfiles is useful for avoiding file breakage during root canal therapy. PMID- 24233204 TI - [Remineralization of enamel promoted by casein phosphopeptide-amorphous calcium phosphate with different concentration of fluorin]. AB - PURPOSE: To evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) combined with different concentrations of fluoride on demineralization of enamel remineralization. METHODS: Extracted premolar teeth for orthodontic reason were immersed into lactic acid gel to prepare artificial white spot lesions. Then the specimens were randomly assigned to 3 groups: 5% CPP ACP group as control, 5% CPP-ACP +500 mg/L F- group and 5% CPP-ACP +900 mg/L F- group, which were measured by micro-hardness tester. SPSS 18.0 software package was used for data analysis. RESULTS: There were significant differences in micro hardness between control group and experimental group 1 and experimental group 2 by SNK-q test (P<0.05). CONCLUSIONS: CPP-ACP can make the demineralization of enamel remineralization occurs. F can promote the CPP-ACP remineralization. The increase of fluoride can make the CPP-ACP remineralization better below 1000-1500 mg/L. PMID- 24233205 TI - [A study of maxillary sinus lateral wall thickness of Han population in Jiangsu region using cone-beam CT]. AB - PURPOSE: To evaluate maxillary sinus lateral wall thickness by use of cone-beam computed tomography (CBCT), in order to provide anatomical basis for preoperative risk assessment and operation guidance of maxillary sinus lifting. METHODS: Using SimPlant software, the 3D images were reconstructed with CBCT images from 412 subjects and the thickness of maxillary sinus lateral wall were evaluated at measurement plane. The data was analyzed with SPSS17.0 software package. RESULTS: Among 412 subjects (824 sides), the mean thickness of maxillary sinus lateral wall at the second premolar (P2), the first molar (M1) and the second molar (M2) was 2.23+/-1.07 mm, 2.19+/-1.45 mm and 1.41+/-0.81 mm, respectively. The thickness of maxillary sinus lateral wall on the left side were significantly different from that on the right side at P2 (P<0.01). Significant gender differences on the thickness of maxillary sinus lateral wall were demonstrated at P2 and M2 (P<0.05), and the thickness in men were thicker than that in women. The thickness of maxillary sinus lateral wall at M1 and M2 were significantly different among different age groups (P<0.05). There was no significant difference on the lateral wall thickness with respect to presence or absence of tooth. CONCLUSIONS: CBCT can accurately measure the thickness of maxillary sinus lateral wall. The mean thickness of lateral wall changes at different reference points. The value at premolar region is greater than that at molar region, and the maxillary sinus lateral wall is the thinnest at M2. There are significant differences in the mean thickness of the lateral wall with respect to age, gender, and side of maxillay sinus. Supported by National Natural Science Foundation of China (81271109), Priority Academic Development Program of Jiangsu Higher Education Institutions (2011-137). PMID- 24233206 TI - [Investigation of dental manpower in non-public dental institutions in Liaoning province]. AB - PURPOSE: To investigate the non-public oral medical institutions in Liaoning province in 2011, and to analyze the status of dental manpower in non-public dental institutions in Liaoning province. METHODS: A mass survey on dental manpower was made in non-public dental institutions in Liaoning province in 2011 by means of questionnaire investigation, which included the institution type, dental devices, and the number, structure, composition, distribution of dental manpower in non-public dental institutions in Liaoning province. Data was entered with EpiData 3.0 and analyzed with SPSS 13.0 software package. RESULTS: There were 1649 non-public dental institutions with 3132 dentists, 1265 nurses, 540 technicians and 3490 dental chairs in Liaoning province. 85.69% of the dental manpower were young and middle-aged. 33.17% of the dentists had primary professional titles, 42.53% of them had college degree and 87.96% of the dentists was general dentistry. In the dental auxiliaries, the primary professional title accounted for the majority. 95.97% of the nurses majored in general dentistry and 60.40% of the nurses' educational background were below junior college degree. 72.59% of the technicians majored in prosthetic dentistry and 67.78% of their educational background were below junior college degree. The ratio of the dentists to nurses to technicians was 6:2:1. The ratio of the nurses to dental chairs was 1:2.76. CONCLUSIONS: The distribution and composition of dental manpower are not reasonable in non-public dental institutions in Liaoning province. We should strengthen effective utilization of oral health resources and the oral health service ability of non -public dental institutions in Liaoning province. Supported by Key Science and Technology Projects of Liaoning Province (2012225015). PMID- 24233207 TI - [Effect of two different kinds of occlusal splints on temporomandibular disorders]. AB - PURPOSE: To investigate the effect of relaxed splint and stabilized splint on the treatment of temporomandibular disorders (TMD). METHODS: A total of 68 TMD patients were divided into 2 groups (30 patients with acute pain and 38 patients with chronic pain) and treated with relaxed splint or stabilized splint. Visual analog scale (VAS) scores and electromyography (EMG) of bilateral anterior temporal muscle (TA) and masseter muscle (MM) were recorded before treatment and 1 month after treatment. The data was analyzed using variance analysis and student's t test with SPSS11.0 software package. RESULTS: At rest position, patients' EMG decreased remarkably (P<0.05) after both kinds of splints treatment. During maximal voluntary clench, the EMG of masticatory muscle (TA, MM) of patients with acute pain and EMG of MM of patients with chronic pain increased significantly after relaxed splint treatment (P<0.05), but only EMG of MM increased significantly after stabilization splint treatment (P<0.05). Patients' VAS scores decreased remarkably after both kinds of splints treatment (P<0.05), but during function, patients' acute pain eased remarkably after relaxed splint treatment (P<0.05). CONCLUSIONS: The relaxed splint and stabilized splint can relax the masticatory muscles and ease TMD pain, but relaxed splint has significant effect on the treatment of acute TMD patients. Supported by Natural Science Foundation of Hainan Province (310126). PMID- 24233208 TI - [Progressively transformed germinal center in oral and maxillofacial region: report of 3 cases]. AB - PURPOSE: To discuss the diagnosis and prognosis of progressively transformed germinal center and emphasize the necessity of long term follow-up after treatment. METHODS: Three patients were diagnosed as progressively transformed germinal center (PTGC) from 2010 to 2012. The clinical characteristics, histological features, differential diagnosis, prognosis were analyzed with review of literatures. RESULTS: Among 3 cases, 2 were found around parotid gland, one was in the neck. All patients were young male adults, who received excisional biopsy and regular histopathological examination. They were followed up for 8 months to 2.5 years, no relapse was found. CONCLUSIONS: PTGC occurs more commonly in young male adults. It always appears as an isolated and painless enlarged lymph node, which responses poorly to antibiotics. The final diagnosis is relied on histopathological and immunocytochemical examinations. Close follow-up is necessary, and attention should be paid to nodular lymphocyte predominant Hodgkin's disease although there is no clear evidence about their relationship of development. Supported by Science and Technology Plan Project of Shaoxing City(2011A23029). PMID- 24233209 TI - [Evidence-based quality assessment of Chinese clinical trials on the effects of stabilization of permanent anterior dental trauma]. AB - PURPOSE: To appraise the quality of Chinese clinical trials during recent 10 years about the treatment of permanent anterior dental trauma with evidence-based quality control methods. METHODS: The CNKI (Chinese National Knowledge Infrastructure) and Wanfang electronic database with key words "permanent anterior dental trauma " were searched. Two hundred and forty-five papers were obtained during recent 10 years, 46 key papers about the treatment of permanent anterior dental trauma were retrieved. The quality of the Chinese clinical trials according to the consolidated standards of reporting trials (CONSORT) and strengthening the reporting of observational studies in epidemiology (STROBE) statement were assessed. RESULTS: Within the 46 key papers, there were 8 randomized controlled clinical trials, while the other 38 papers were observational studies. It was hard to evaluate precisely due to the lack of scientific information. The randomized controlled trials lacked details for randomization, allocation concealment and blinding compromised the quality. CONCLUSIONS: For the clinical studies about the effects of stabilization of permanent anterior dental trauma, the study quality needs to be improved, and progress should be made both in the clinical study design and the paper writing. Supported by Grants for Selecting and Training Outstanding Faculty in Shanghai Universities(jdy10048). PMID- 24233210 TI - [Caries prevalence of the first permanent molar among 7-9 years old Uygur children in Urumqi, Xinjiang Autonomous Region]. AB - PURPOSE: To investigate the caries status of the first permanent molar among 7-9 years old Uygur children in Urumqi, Xinjiang Autonomous Region, and provide bases for the oral health care of children in Urumqi. METHODS: The study was conducted in a preschool in Urumqi, Xinjiang Autonomous Region, involving 1600 children aged among 7-9 years old. The dental caries of these children were examined by 2 general dentists according to the criteria of the Third National Epidemiological Survey in China. Data were analyzed by SPSS16.0 software package for X(2) test and student's t test. RESULTS: The prevalence of caries in the first permanent molar among these children was 26.50%, with a mean DMFT of 0.44. The caries prevalence in boys was 22.98% and 30% in girls (P<0.05). The DMFT in boys and girls was 0.41, 0.47, respectively. The caries prevalence increased along with the increase of age. The caries prevalence of 9-year-old children was significantly higher than that in 7 and 8-year-old children (P<0.05). CONCLUSIONS: The caries prevalence of the first permanent molar among 7-9 years old children in Urumqi, Xinjiang Autonomous Region is high. It is necessary to enhance the early guidance for the Uygur children to develop good oral health habits and status. Supported by 2010 West China Children's Oral Disease Interventional Polit Project. PMID- 24233211 TI - [Establishment and management of electronic appointment library for dental implant patients]. AB - PURPOSE: To design an excel form which can prompt dental implant patient appointment through color change, which can scientifically manage implant EMR library through appropriate interlinkage and number. METHODS: An excel form based on operating system Windows XP was designed and software 2003 Microsoft excel was used, which was configured to change color with the passage of time by the use of command "conditional format". RESULTS: An excel form was designed. The color turned to red automatically on the day the patient underwent implant surgery. It turned to yellow when the patient recalled 2 weeks after the first operation, to green when the patient underwent secondary operation. It was designed to be gray when all the procedures of implant restoration was finished. In addition, we could know patients' main implant situation through directly opening his EMR when clicking on his name or number. CONCLUSIONS: Dentists can remind the implant patient appointment schedule through color change of an excel form, and can consult the implant patient EMR directly through interlinkage or number. PMID- 24233212 TI - [Application of orthodontic fixed device in restoring teeth space in children]. AB - PURPOSE: To assess the effect of orthodontic fixed device in restoring teeth space in children. METHODS: Brackets with archwire and open coil spring were used to restore teeth space loss in 8 cases. RESULTS: In all 8 cases, 6 cases achieved success, 1 case had improvement and 1 case had failure. Within these cases, the fastest restoring time was 2 months and the slowest restoring time was 7 months. CONCLUSIONS: It is an ideal method to restore teeth space with orthodontic fixed device. It is a simple, fast and economic for early orthodontic treatment. Due to the fewer cases, further study is needed. PMID- 24233213 TI - [Oxidative stress and susceptibility of periodontal disease]. AB - PURPOSE: To investigate the relationship between dietary antioxidant status and susceptibility of periodontal disease in humans. METHODS: Fifty patients with moderate-to-sever periodontal disease and 50 subjects without periodontal disease were enrolled in this study. Food frequency questionnaire and 72-hour diet recall were conducted to study the dietary pattern and antioxidant nutrients intake in patients and healthy subjects. Nutritional status including vitamins, mineral substance, and antioxidant enzymes in these 2 groups were analyzed in serum and saliva samples by liquid chromatography-mass spectrometry (LC-MS). SPSS 19.0 software package was used for paired t test. RESULTS: Compared with the control group, the chronic periodontal group had lower levels of potatoes, aquatic product, milk, soy, fresh vegetables, fruit and vitamin supplements intake(P<0.05). Through food components analysis we found that the intake of vitamin A, C, B2, E, calcium, magnesium, copper, selenium was significantly lower in the chronic periodontal disease group than that in the control group (P<0.05). Biochemical analysis demonstrated that antioxidant nutrient levels including antioxidant enzyme SOD in serum and saliva together with magnesium, calcium, manganese, zinc in saliva were significantly lower in disease periodontal group than in the control group (P<0.05). CONCLUSIONS: Oxidative stress plays an essential role in the occurrence and development of periodontal disease. The antioxidant nutrients may help to protect paradentium. Supported by Research Fund from Shanghai Municipal Health Bureau (20114103). PMID- 24233214 TI - [Clinical application of optimal designed Upcera super transparent zirconia all ceramic restorations]. AB - PURPOSE: To summarize the clinical application of special designed Upcera ST zirconia all-ceramic restorations in cases with limited occlusal space. METHODS: Twenty-one patients with 23-unit restorations were enrolled in this study. First, the shape of abutment teeth and diagnostic wax-up were captured and digitized by Sirona inEos system. Then, each individually shaped framework to grant a defined ST zirconia base core was created by the reduced program of inLab software. Finally, all restorations were veneered with VITA VM9 and evaluated at placement using modified U.S.Public Health Service Criteria 6 to 12 months after restoration. Patients were inquired with satisfaction questionnaire at the same time. RESULTS: During 6 to 12 months of follow-up visit, except for one of 23 restorations was rated as failure by fractured root, none was replaced due to framework fracture or unrestorable delamination of the ceramic veneer. The shape and colour of all restorations were satisfactory. CONCLUSIONS: To ensure optimum long-term clinical results of all-ceramic crown restorations, one important key is to overcome the fragmentation of dental prosthesis through modifying the shape of restoration. Based on the results of this study, the specially designed processing technology shows sufficient stability for ST zirconia all-ceramic restorations within a short term, which is deserved to be used in selected cases. PMID- 24233215 TI - [Evaluation of clinical efficacy of casting pure titanium ring on reparation of subgingival residual root]. AB - PURPOSE: To explore treatment regime and curative effect of the casting pure titanium ring on reparation of subgingival residual root. METHODS: Thirty-two teeth were selected for reparation of subgingival residual root after root canal therapy in our department during 2008-2010. The teeth were restored with casting pure titanium ring, glass fiber post and all-ceramic crown. The patients were recalled 12 and 24 months after placement of the pure titanium ring. Gingival crevicular fluid(GCF) samples were collected by filter paper strips. Then the weight of GCF was detected and the gingival index was recorded. The data was analyzed for paired samples t test by SPSS17.0 software package. RESULTS: There was no significant difference in the weight of GCF and the gingival index before and after placement of pure titanium ring (P<0.05). CONCLUSIONS: By using pure titanium ring, most subgingival residual root after root canal therapy can be rehabilitated and function well for long time. PMID- 24233216 TI - [Clinical evaluation of denture adhesive combined with oral wetting spray on satisfaction of complete denture in xerostomia patients]. AB - PURPOSE: The purpose of this study is to investigate the effect of denture adhesive and oral wetting spray on the satisfaction of wearing complete denture in xerostomia patients. METHODS: Ten edentulous patients who suffered from deficient residual alveolar ridge and xerostomia with poor retention and stability of complete dentures or mandibular complete dentures were employed to assess the differences of satisfaction after use of denture adhesive in their dry oral cavity for 1 week, and use of denture adhesive combined with oral wetting spray for 1 month, 3 months and 6 months by using satisfaction questionnaire. The statistical analysis was carried out with SPSS17.0 software package. RESULTS: Six months after the use of denture adhesive combined with oral wetting spray, the satisfaction of complete denture was significantly improved in respects of general satisfaction, retention of mandible denture, comfort and mastication improvement than that before application (P<0.05). But 1 week after the use of denture adhesive alone, the satisfaction of comfort reduced than that before application (P<0.05). CONCLUSIONS: Denture adhesive combined with oral wetting spray can be used to improve the satisfaction of xerostomia patients treated with complete denture who suffered from deficient residual alveolar ridge. PMID- 24233217 TI - [Common errors and mistakes seen in Chinese prosthodontic articles]. AB - As an editor of dental journals, the author found that some inappropriate writing and mistakes existed in many articles, which reduced the quality of the published papers. The problems can be divided into three categories: irregular terminology; not concise, inaccurate description; improper use of punctuation and title code. They were illustrated respectively in this article for readers to avoid these mistakes in the future. PMID- 24233218 TI - [Promote the development of dental education via National Board Dental Examinations]. AB - PURPOSE: By evaluating the data of National Board Dental Examinations over recent 3 years, the disadvantages in the present dental education were analyzed and improvement schemes were proposed. METHODS: The enrollment system, faculty, facility and equipment were evaluated for dental schools in Hubei province from 2008 to 2010, including 4 dental schools and 7, dental professional schools. The passing rate of National Board Dental Examinations and National Board Dental Assistant Examinations were summarized. RESULTS: Lack of faculty resources and over-enrollment were found in 7 dental professional schools. In dental professional schools, the number of dental simulation units compared to number of students enrolled was as low as 1:0.15. The passing rate of National Board Dental Examinations was 27.9%-30.1%, and the passing rate of National Board Dental Assistant Examinations was 32.5%-40.7%. CONCLUSIONS: The passing rate of National Board Dental Examinations and National Board Dental Assistant Examinations is limited mainly by the lack of faculty and equipment resources and over enrollment. We propose that basic knowledge shall be enhanced in dental professional schools. In addition, the target of education should be shot as high as that in dental schools. PMID- 24233219 TI - [Observation of clinical effect of vertically fractured molar teeth treated with elastic ligation]. AB - PURPOSE: To evaluate the clinical effect of vertically fractured posterior teeth treated with elastic ligation. METHODS: Eighty-six vertically fractured posterior teeth were chosen to be treated with elastic ligation for external fixation before root canal therapy (RCT), and then full crown prostheses were made for rehabilitation. RESULTS: The success rate after 1 year, 2 years and 3 years were 97.67%, 93.02% and 88.37%, respectively. CONCLUSIONS: Elastic ligation for vertically fractured posterior tooth before RCT can effectively prevent tooth fracture during treatment and preserve the tooth for functional use. PMID- 24233220 TI - Introduction of foreign genes into Pharbitis nil calli using a vector derived from Agrobacterium pTi. AB - Transgenic calli of Pharbitis nil which grow in the presence of kanamycin were obtained by introduction of plasmid pBI121, which carries kanamycin resistance and the gene for beta-glucuronidase. The calli were shown to have fragments of vector DNA in their genome and high levels of beta-glucuronidase activity. This is the first report of the introduction of T-DNA into P. nil and the T-DNA has been shown to be integrated without apparent rearrangement in its genome. The range of copy numbers was between 3 and 5. The beta-glucuronidase activities measured were about 10 times higher than those of transgenic tobacco by introduction of the same plasmid as previously described by Jefferson et al. (1987). Thus, the widely used CaMV 35S promoter also appears to be very active in P. nil. PMID- 24233221 TI - Efficient production of haploid wheat (Triticum aestivum) through crosses between Japanese wheat and maize (Zea mays). AB - Four Japanese wheat varieties, three crossable and one non-crossable with Hordeum bulbosum, were pollinated with maize pollen of 5 genotypes. By the application of 2,4-dichlorophenoxyacetic acid after pollination, embryos kept developing on wheat plants until 14 days after pollination. The frequency of embryo formation was significantly different among the maize genotypes, varying from 18.0% to 31.9%, but not among the wheat varieties. By bagging spikes with flag leaves the frequency of embryo formation was increased by about 7%. Ten- to twelve-day-old embryos gave higher frequencies of plant formation (83.6%) than 14-day-old embryos(50.0%). All 6 regenerated plants investigated cytologically were found to be haploid. Twelve of the 14 colchicine-treated plants produced florets setting seeds. The overall efficiency of our procedure is considered to be higher than that reported by Laurie and Bennett (1988). PMID- 24233222 TI - Induction of somatic embryogenesis in leaf-derived callus of Vicia narbonensis L. AB - A method for the induction of somatic embryogenesis in callus cultures, using explants from mature leaves of Vicia narbonensis L., is described. Callus developed on a solid medium (Murashige and Skoog 1962), which was supplemented with low concentrations of picloram and benzylaminopurine. Subsequent culture was carried out in different liquid media (culture length four months). The gradual reduction of auxin and cytokinin concentrations, and the addition of glutamine and pyridoxal.HCl were favourable. Somatic embryos appeared on solid media without phytohormones. PMID- 24233223 TI - Somatic embryogenesis and plantlet regeneration in Cornus florida. AB - Somatic embryos were initiated from 12 to 15 weeks postanthesis (WPA) zygotic embryos of Cornus florida L. (flowering dogwood) cultured on Murashige-Skoog (MS) or Schenk and Hildebrandt (SH) medium amended with either 3 mg/L 2,4-D or 5 mg/L 2,4-D and 1 mg/L kinetin. White, opaque globular and early cotyledonary stage embryos were formed directly on detached cotyledons from 2 of the 5 trees sampled after 7 weeks of culture. Morphologically mature embryos developed after an additional 4 weeks incubation on medium without growth regulators; however, many of the embryos were fused in pairs along the entire length of the hypocotyl radicle axis. Indirect embryogenesis was observed from callus cultures initiated from 9 to 15 WPA zygotic embryos. These cultures have continued to produce embryos for 16 months. Many of the embryos formed roots on germination medium, but only 12% formed plantlets and none developed past the first true leaf stage. PMID- 24233224 TI - Specificity of strain and genotype in the susceptibility of pea to Agrobacterium tumefaciens. AB - To determine the best combination for potential use in transformation of Pisum sativum L., 13 genotypes were inoculated with wild-type Agrobacterium tumefaciens strains A281, C58 and Ach5. A281 appeared to be the most virulent strain, as determined by size and number of tumours, followed by C58 and Ach5. Genotypes differed considerably in their response to inoculation and genotype x strain interaction was evident. Genotypes also responded differently to in vivo or in vitro inoculation. Axenic calli from tumours could be grown on hormone-free medium and the presence of the specific opines for each strain in the callus indicated successful transfer and expression of T-DNA. Southern blot analysis of DNA from callus of A281-inoculated material showed that both TR and TL T-DNA had been incorporated into the pea genome. PMID- 24233225 TI - Regeneration of Medicago truncatula from tissue culture: increased somatic embryogenesis using explants from regenerated plants. AB - Plant regeneration has been achieved by somatic embryogenesis in Medicago truncatula Gaertn. (barrel medic) c.v. Jemalong, an annual legume species. Regenerated plants were obtained from cultured leaf tissue explants on a four step modified B5 basal medium. Induction of embryo formation occurred on a medium containing 10 MUM NAA and 10 MUM BAP, and embryo maturation was promoted after transfer to a medium containing 1 MUM NAA and 10 MUM BAP. Shoot development, secondary somatic embryogenesis and occasional plantlet development occurred on a subsequent transfer to 0.1 MUM NAA and 1 MUM BAP. Plantlet formation could also be completed by transfer of well developed shoots to 0.05 MUM NAA. A high frequency of primary somatic embryos could only be obtained by using the same culture protocol with tissue from regenerated plants. Explants from regenerated plants showed a large increase in the number of primary embryos per callus and the number of calli producing embryos. Explants from plants derived from the seed of one regenerated plant also showed increased embryo formation. Although high embryo formation rates can be reproducibly obtained from this seed, embryo conversion rates to plants are currently low. PMID- 24233226 TI - O-acetyl-salicylic acid promotes colony formation from protoplasts of an elite maize inbred. AB - The salicylic acid derivative acetylsalicylic acid (ASA) was found to promote colony formation from protoplasts isolated from embryogenic suspension cultures of an elite maize inbred line. The drug was most effective at concentrations of 30-100 mg/l, and increases of more than 20-fold in the number of colonies recovered from protoplasts were obtained. The rate of growth of protoplast derived cell colonies was not affected. PMID- 24233227 TI - Characterization of immature embryos of interior spruce by SDS-PAGE and microscopy in relation to their competence for somatic embryogenesis. AB - SDS-PAGE analysis of total proteins from cotyledonary embryo explants reveals that their competence to form somatic embryos is limited to a specific stage of development prior to the accumulation of storage proteins. When protein profiles of embryo explants of different open pollinated families from the same collection date are compared, there is a close relationship between the absence of storage proteins and their ability to produce embryogenic callus. In addition, the appearance of storage proteins in embryos from subsequent collections is associated with their loss of competence. Light microscopy combined with staining for total protein demonstrates that competent immature embryos have cotyledons but do not contain protein bodies. PMID- 24233228 TI - Embryogenesis and plant regeneration from tissue culture of Canada wildrye, Elymus canadensis L. AB - Somatic embryogenesis and plant regeneration of Canada wildrye (Elymus canadensis L.) from tissue culture was investigated by culturing immature embryos and inflorescences on MS medium containing 2 mg/l 2,4-D. The optimum size of explants for maximum embryogenic callus formation was 1.0 to 1.5 mm for embryos and 4 to 6 cm for inflorescences. Plant regeneration from the subcultured embryogenic callus was attempted monthly using hormone-free MS medium or MS medium with 0.5 mg/1 2,4 D and 0.3 mg/l GA3. Three hundred and fifty seven plantlets were regenerated from the callus cultures of both explant sources during a six month period. Ten chlorophyll deficient plants accounting for 2.8% of the total regenerants were observed. One plant with white striped leaves survived and was found to be an octoploid. PMID- 24233229 TI - Stable transformation of maize: the impact of feeder cells on protoplast growth and transformation efficiency. AB - The importance of cell culture conditions, including the use of feeder cells, on protoplast growth and transformation in maize (Zea mays L.) was investigated. Total GUS activity, measured two days after transformation, was five-fold higher in protoplasts cultured on feeder cells compared to those grown in the absence of feeder cells. Since the specific activity of GUS was only slightly higher in the transformed protoplasts plated over feeder cells, the stimulation in transient gene expression resulted mainly from the improved environment provided by the feeder system. For stable transformation, either PEG treatment or electroporation of protoplasts was used to introduce the neo gene. When PEG was used, over 85% of the putative transformants (resistant to kanamycin) contained the neo gene. The combination of PEG transformation and the optimized cell culture protocol using feeder cells enabled the selection of about 100 stably transformed lines per gFW of cells. Electroporation was less efficient. PMID- 24233230 TI - Plant regeneration through somatic embryogenesis from suspension cultures of a minor millet, Paspalum scrobiculatum. AB - Compact, friable and embryogenic calli were initiated from immature inflorescences and young leaf bases of one week old seedlings of Paspalum scrobiculatum cultured on MS medium supplemented with 2,4-D. A stable, embryogenic suspension culture was initiated from these calli and maintained in a liquid version of the same MS medium. Embryogenic calli and somatic embryos were obtained by plating suspension culture cells onto semi-solid medium containing 2,4-D. Complete, normal plantlets developed on 2,4-D free medium at a high frequency from somatic embryos. NAA and BAP in the medium promoted plant development. PMID- 24233231 TI - Tissue culture and plant regeneration of watermelon (Citrullus vulgaris Schrad. cv. Melitopolski). AB - Plants were regenerated from cotyledon and hypocotyl explants of watermelon (Citrullus vulgaris). The explants were cultured on a Murashige and Skoog's basal nutrient medium supplemented with auxin, cytokinin and auxin-cytokinin combinations. Green healthy nodular and compact callus was obtained in medium containing naphthalene acetic acid and benzylaminopurine. Shoot differentiation and root differentiation from the cotyledon and hypocotyl after callus formation in different media containing benzylaminopurine or naphthalene acetic acid, respectively. Shoot formation required benzylaminopurine. Kinetin proved ineffective in inducing shoot buds or shoots. Root differentiation occurred in a medium containing naphthalene acetic acid or indole acetic acid. There was a greater proliferation of roots on medium supplemented with naphthalene acetic acid. The regenerated shoots developed roots when transferred to medium containing naphthalene acetic acid and complete plantlets could be transferred to soil for further growth. PMID- 24233232 TI - Virulence of Agrobacterium tumefaciens strains with Brassica napus and Brassica juncea. AB - Brassica napus and Brassica juncea were infected with a number of Agrobacterium tumefaciens strains. Tumourigenesis was very rapid and extremely efficient on B. juncea with all but one of the strains. Tumourigenesis on B. napus varied widely. It was very efficient with the nopaline strains, was reduced with the succinamopine strain A281 and was very weak with the octopine strains. The latter observation was confirmed with six different B. napus rapeseed cultivars. The selectivity was due to differences in the virulence of Ti plasmids with B. napus, rather than the tumourigenicity of the T-DNA or virulence of the chromosomal genes associated with the strains. An exception was strain LBA4404. The virulence of the octopine strains was increased by coinfection with more virulent disarmed strains and by induction with acetosyringone. PMID- 24233233 TI - Isolation, culture, and regeneration of plants from potato protoplasts. AB - A technique is described for the routine isolation of protoplasts from storage parenchyma cells of potato tubers grown in vitro. The protoplasts typically contained many starch grains. On culture, most of the starch grains were metabolised during the first 7 days, after which the cells began to divide. Following further culture, protoplast-derived colonies and calli were obtained, from which shoots and intact plants were regenerated. Cytological study of regenerated plants showed that the majority were octaploid or aneuploid at the octaploid level. This aspect is compared with plants regenerated from mesophyll protoplasts of potato. The use of tuber protoplasts for studies on tissue specific transient gene expression of chimeric gene constructs, following their introduction into the protoplasts by electroporation, is discussed, together with the uses of tuber protoplasts in fundamental physiological and biochemical studies. PMID- 24233234 TI - Errata. PMID- 24233236 TI - Cardiovascular responses, perceived exertion and technical actions during small sided recreational soccer: effects of pitch size and number of players. AB - The aim of this study was to determine the cardiovascular, perceived exertion and technical effects of altering pitch size and number of players in recreational soccer match-play. The further aim was to evaluate to what extent exercise intensity during various game formats corresponds to the recommended intensity level for cardiovascular fitness improvement. Ten male recreational players aged 31.7+/-7.6 years (mean +/- SD) completed four variations of small-sided games (except for goalkeepers, 5-a-side and 7-a-side on small and large pitches) during which heart rate, perceived exertion and technical actions were evaluated. Two way analysis of variance on repeated measures was applied to collected data. The results indicated that an average workload expressed as heart rate and percentage of heart rate reserve during 5-a-side games was higher than for 7-a-side games. The rate of perceived exertion values were moderate and similar for all formats of games. The players performed more dribbling and successful passes, but fewer unsuccessful passes during 5-a-side games. Furthermore, the number of ball possessions and unsuccessful passes was higher on a small pitch than on a large one. Consequently, the current findings suggest that, independent of pitch size, the cardiovascular demands imposed on participants increase when the game is played with fewer players. However, all formats of recreational soccer can be used as an effective activity to promote cardiovascular fitness. Finally, participants may have more chance to perform basic technical actions during 5-a side games on small and large pitches. PMID- 24233237 TI - Sex pheromone component ratios and mating isolation among three Lygus plant bug species of North America. AB - The plant bugs Lygus hesperus, Lygus lineolaris, and Lygus elisus (Hemiptera: Miridae) are major pests of many agricultural crops in North America. Previous studies suggested that females release a sex pheromone attractive to males. Other studies showed that males and females contain microgram amounts of (E)-4-oxo-2 hexenal, hexyl butyrate, and (E)-2-hexenyl butyrate that are emitted as a defense against predators. Using gas chromatography-mass spectrometry, we found that female L. lineolaris and L. elisus have a 4:10 ratio of hexyl butyrate to (E)-2 hexenyl butyrate that is reversed from the 10:1 ratio in female L. hesperus (males of the three species have ~10:1 ratio). These reversed ratios among females of the species suggest a behavioral role. Because both sexes have nearly equal amounts of the major volatiles, females should release more to attract males. This expectation was supported because L. hesperus females released more hexyl butyrate (mean of 86 ng/h) during the night (1800-0700 hours) than did males (<1 ng/h). We used slow-rotating pairs of traps to test the attraction of species to blends of the volatiles with a subtractive method to detect synergism. Each species' major butyrate ester was released at 3 MUg/h, the minor butyrate according to its ratio, and (E)-4-oxo-2-hexenal at 2 MUg/h. The resulting catches of only Lygus males suggest that (E)-4-oxo-2-hexenal is an essential sex pheromone component for all three species, (E)-2-hexenyl butyrate is essential for L. elisus and L. lineolaris, and hexyl butyrate is essential for L. hesperus. However, all three components are recognized by each species since ratios of the butyrate esters are critical for conspecific attraction and heterospecific avoidance by males and thus play a role in reproductive isolation among the three species. Because L. hesperus males and females are known to emit these major volatiles for repelling ant predators, our study links defensive allomones in Lygus bugs with an additional use as sex pheromones. PMID- 24233238 TI - In vitro analysis of the complete CIDE domain interactions of the Drep system in fly. AB - CIDE domain containing proteins are involved in apoptosis and lipid metabolism, and four CIDE containing proteins, Drep1, Drep2, Drep3, and Drep4, have been identified in fly. In this study, we found that Drep3 interacts with Drep4 via the CIDE domain specifically, which completes the interaction map of Drep system in fly, cyclic interactions: Drep1-Drep2-Drep3-Drep4-Drep1. In addition, we analyzed the dynamic stoichiometry changes of Drep proteins upon binding to their binding partners. Our current studies will help us to understand Drep system in fly as well as CIDE domain for protein-protein interactions. PMID- 24233239 TI - Enzyme-processed Korean Red Ginseng extracts protects against skin damage induced by UVB irradiation in hairless mice. AB - UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-1 level, while accelerated procollagen type I, transforming growth factor-beta1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes. PMID- 24233240 TI - Angiotensin-converting enzyme inhibitor nephrotoxicity in neonates with cardiac disease. AB - Angiotensin-converting enzyme inhibitors (ACEi) are commonly used for pediatric cardiology patients. However, studies examining their safety for neonates with cardiac disease are scarce. The current study aimed to test the hypothesis that ACEi-mediated nephrotoxicity occurs in neonates and may be underappreciated in this population. A retrospective review of 243 neonates with cardiac disease between 2007 and 2010 was performed. Demographic data, weight, length, captopril and enalapril dosing, serum [K+], serum creatinine, and concomitant medications during ACEi therapy were recorded and analyzed. Body surface area (BSA), creatinine clearance (CrCl), and change in [K+] were calculated. The age range of neonates at ACEi initiation was 15.9-18.1 days. The inclusion criteria was met by 206 neonates: 168 term (82%) and 38 preterm (18%) newborns. Of these neonates, 42% were female, and all the patients had a BSA smaller than 0.33 m2 (a group known to have relative renal insufficiency). The mean dose of enalapril was 0.08 +/- 0.007 mg/kg for the preterm neonates and 0.08 +/- 0.003 mg/kg for the term neonates. The mean dose of captopril was 0.07 +/- 0.009 mg/kg for the preterm neonates and 0.13 +/- 0.019 mg/kg for the term neonates. A significant decrease in CrCl occurred for both the preterm (p < 0.01) and term (p < 0.001) neonates while they were receiving ACEi. However, the two groups did not differ significantly (p = 0.183). Nearly 42% of all the patients showed renal risk, with approximately 30% demonstrating renal failure by modified pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease) criteria. Despite the lack of significantly different CrCl, the premature neonates were more likely to experience ACEi-related renal failure by pRIFLE (55%) than their term counterparts (23%; p < 0.001). Despite its common use for term neonates with cardiac disease, ACEi should be used cautiously and only when indications are clear. These results also raise the question whether ACEi should be used at all for preterm neonates. PMID- 24233241 TI - PI3KCA mutation status is of limited prognostic relevance in ER-positive breast cancer patients treated with hormone therapy. AB - PI3K/AKT/mTOR pathway alterations are frequent in patients with infiltrating breast cancer (IBC). Their clinical and pathological relevance has been insufficiently documented. We evaluated PI3KCA for mutations and the expression of PTEN, AKT, mTOR and p70S6K by immunohistochemistry in 246 IBC patients treated with hormone therapy (median follow-up, 97 months). A PI3KCA mutation was observed in 50 out of 229 informative cases (21.8 %), PTEN loss in 107 out of 210 (51 %), moderate/high level of expression of AKT in 133 out of 188 (71 %), moderate/high level of expression of mTOR in 173 out of 218 (79 %) and moderate/high level of expression of p70S6K in 111 out of 192 cases (58 %). PI3KCA mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling. The expression of p70S6K was associated with a high level of mTOR immunoreactivity, and high PTEN expression was associated with high AKT expression level. Univariate analysis showed that PI3KCA mutation status was not associated with clinical outcome in the series as a whole or in the node-negative subgroup. However, in the node-positive subgroup, exon 9 PI3KCA mutation was associated with unfavourable overall survival (OS), although its impact on the final model in multivariate analysis seemed to be limited. Of the other markers, only high p70S6K expression was associated with a significantly prolonged OS. PI3KCA mutation status is of limited prognostic relevance in oestrogen receptor-positive breast cancer patients treated with hormone therapy. PMID- 24233242 TI - Complexity analysis and parameter estimation of dynamic metabolic systems. AB - A metabolic system consists of a number of reactions transforming molecules of one kind into another to provide the energy that living cells need. Based on the biochemical reaction principles, dynamic metabolic systems can be modeled by a group of coupled differential equations which consists of parameters, states (concentration of molecules involved), and reaction rates. Reaction rates are typically either polynomials or rational functions in states and constant parameters. As a result, dynamic metabolic systems are a group of differential equations nonlinear and coupled in both parameters and states. Therefore, it is challenging to estimate parameters in complex dynamic metabolic systems. In this paper, we propose a method to analyze the complexity of dynamic metabolic systems for parameter estimation. As a result, the estimation of parameters in dynamic metabolic systems is reduced to the estimation of parameters in a group of decoupled rational functions plus polynomials (which we call improper rational functions) or in polynomials. Furthermore, by taking its special structure of improper rational functions, we develop an efficient algorithm to estimate parameters in improper rational functions. The proposed method is applied to the estimation of parameters in a dynamic metabolic system. The simulation results show the superior performance of the proposed method. PMID- 24233243 TI - Reply to: The rate of PCr resynthesis is not a reliable index of skeletal muscle oxidative capacity. PMID- 24233244 TI - The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for oxidative stress, low-grade inflammation and nitric oxide production. AB - AIMS: To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM). METHODS: Twenty-five sedentary, obese (BMI > 30 kg/m2) males (52.8 +/- 7.2 years); 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max; 30-40% VO(2max)) or moderate (T(vent); 55-65 % VO(2max)) intensity. Before and after training, blood and muscle samples (v. lateralis) were collected. RESULTS: Baseline erythrocyte glutathione was lower (21.8 +/- 2.8 vs. 32.7 +/- 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 +/- 52.1 vs. 75.5 +/- 41.6 nmol/ml). Plasma catalase increased in T2DM after T(vent) training (from 0.98 +/- 0.22 to 1.96 +/- 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 +/- 2.78 vs. 12.34 +/- 3.56 MUmol/l). Training at T(vent) increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers. CONCLUSION: Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T(vent). Non diabetics responded to T(vent) training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention). PMID- 24233246 TI - Computation and measurement of slant specified by linear perspective. AB - One of the striking features of vision is that we can experience depth in two dimensional images. Since the Renaissance, artists have used linear perspective to create sensations of depth and slant. What is not known is how the brain measures linear perspective information from the retinal image. Here, an experimental technique and geometric computations were used to isolate slant related to linear perspective from slant induced by other cues. Grid stimuli, designed to induce strong impressions of slant, were sufficiently simple to allow accurate predictions on the basis of numeric computations. Measurement of slant about the vertical axis as functions of slant depicted on the screen and slant of the screen relative to the observer showed that linear perspective explained 95% of the slant judgments. Precision and accuracy of the judgments suggest a neural substrate that is able to make highly accurate comparisons between orientations of lines imaged at different retinal locations. The neural basis of slant from the linear perspective has not yet been clarified. Long-range connections in V1, however, and cells in V2, V4, lateral occipital cortex, and caudal intraparietal sulcus have features that suggest an involvement in slant perception. PMID- 24233245 TI - Scotopic hue percepts in natural scenes. AB - Traditional trichromatic theories of color vision conclude that color perception is not possible under scotopic illumination in which only one type of photoreceptor, rods, is active. The current study demonstrates the existence of scotopic color perception and indicates that perceived hue is influenced by spatial context and top-down processes of color perception. Experiment 1 required observers to report the perceived hue in various natural scene images under purely rod-mediated vision. The results showed that when the test patch had low variation in the luminance distribution and was a decrement in luminance compared to the surrounding area, reddish or orangish percepts were more likely to be reported compared to all other percepts. In contrast, when the test patch had a high variation and was an increment in luminance, the probability of perceiving blue, green, or yellow hues increased. In addition, when observers had a strong, but singular, daylight hue association for the test patch, color percepts were reported more often and hues appeared more saturated compared to patches with no daylight hue association. This suggests that experience in daylight conditions modulates the bottom-up processing for rod-mediated color perception. In Experiment 2, observers reported changes in hue percepts for a test ring surrounded by inducing rings that varied in spatial context. In sum, the results challenge the classic view that rod vision is achromatic and suggest that scotopic hue perception is mediated by cortical mechanisms. PMID- 24233247 TI - Morphometrics and ultrastructure of myocardial tissue in Notothenioid fishes. AB - Antarctic fish of the family Channichthyidae (Icefishes) lack the respiratory pigments haemoglobin and myoglobin. The morphometrics and ultrastructure of the ventricular myocardium of a benthic icefish,Chaenocephalus aceratus has been compared with that of a red-blooded Notothenioid fish,Notothenia neglecta, of similar habit.The mass of ventricular muscle as a percentage of bodyweight is 3 times greater in adultC. aceratus (0.32%) thanN. neglecta (0.11%). Myoglobin concentration in the ventricle ofN. neglecta, 20 nmoles/g, is comparable to that of temperate teleosts with similar activity patterns. The volume and surface densities of mitochondria are 41.5% and 0.32 MUm(-1) for Icefish and 25% and 0.15 MUm(-1) forN. neglecta, Cytochrome oxidase activities are similar in the two tissues whilst the volume density of myofibrils is higher forN. neglecta (47%) thanC. aceratus (29.9%).The proliferation of mitochondria in the myocardium of Icefish will reduce the diffusion path-length for oxygen between ventricular lumen and the outer mitochondrial membrane and may compensate for the absence of myoglobin. PMID- 24233248 TI - Seasonal, reproductive, and nutritional influences on muscle "buffering capacity" in yellow perch (Perca flavescens). AB - "Effective non-bicarbonate" buffering capacity (or buffer value) was measured in white muscle of yellow perch (Perca flavescens) by titrations with mineral acid and base in a carbon-dioxide free, closed system. Yellow perch were collected at three month intervals throughout 1983 from an acidic lake (pH ~ 4.6) and two alkaline lakes (pH ~ 7.8) in northern Wisconsin. "Buffering capacity" was also determined for white muscle of perch kept in the laboratory under different regimes of temperature and ration. The mean "buffering capacity" of white muscle from yellow perch taken directly from natural environments ranged from 40.7 +/- 3.1 (SD) slykes in March of 1983 to 53.7 +/- 2.8 (SD) slykes in July of that year. These changes in "buffering capacity" were strongly correlated with water temperature. Egg production and thirty-day laboratory starvation produced significant decreases in "buffering capacity" and increases in the water content of yellow perch muscle. Fed perch in the laboratory had a temperature dependent "buffering capacity" similar to "field caught" fish. "Buffering capacity" of white muscle did not differ between yellow perch from acidic and alkaline lakes. Investigators using "buffering capacity" as a gauge of species differences in metabolic potential, should be wary of seasonal and reproductive factors that might alter their conclusions. PMID- 24233249 TI - Water balance in developing eggs of the codGadus morhua L. AB - Measurements of yolk osmolality from the embryo of codGadus morhua L. revealed significant variations in the hyposmolality during the embryonic development. The embryo proved to have an extremely low water permeability, protecting it from dehydration in the hyperosmotic seawater. The effect of temperature on the water permeability is high, expressed by an exceptionally high activation energy for water transfer. The agreement between embryonic volume decrease and diffusion permeability during the first 8-10 days after fertilization indicates that no water uptake mechanism is present at this time, thus leaving the embryo fully dependent on internal water stores. The cod egg is buoyant in seawater throughout development. The mechanism for providing hydrostatic lift is the large volume of diluted tissue water located in the yolk and subdermal spaces. PMID- 24233250 TI - Whole animal transepithelial potential (TEP) of coho salmon during the parr-smolt transformation and effects of thyroxine, prolactin and hypophysectomy. AB - Whole animal transepithelial potentials (TEP) of yearling coho salmon (Oncorhynchus kisutch) in fresh water and after transfer to seawater were recorded throughout parr-smolt transformation (smoltification) from February to August 1984, along with plasma Na(+) and Cl(-) concentrations and osmolality. Based on plasma ion regulation in seawater, the yearling coho in this study completed smoltification and attained sea-water adaptability in April. TEP in freshwater fish decreased (became inside-negative) after smoltification, and the TEP increased significantly (P < 0.01) after seawater transfer. When fish were transferred into seawater, thyroxine increased TEP of the transferred smolts by approximately 30% over the control level (P < 0.01) in April, but this did not occur when freshwater postsmolts were transferred in July and August. Hypophysectomy increased TEP (P < 0.01) in fresh water; it did not affect the TEP of the fish after seawater transfer. Ovine prolactin (3 MUg/g body weight) implanted into seawater-adapted fish caused a reduction in TEP (P < 0.01) when fish were exposed to fresh water. Whole-animal TEP appears to provide a valuable index of the completion of smoltification (April-May) and a useful tool for investigating the endocrine control of salmonid osmoregulation. PMID- 24233251 TI - Variations in hepatic metallothionen, zinc and copper levels during an annual reproductive cycle in rainbow trout,Salmo gairdneri. AB - The normal variations in hepatic levels of metallothionein, zinc and copper were studied during an annual reproductive cycle in rainbow trout of both sexes. In female fish, the total hepatic zinc levels closely followed the estradiol-17beta and the LSI levels. Hence, the zinc levels rose in September, peaked in December and dropped in January. No distinct peaks were, however, observed in the whole liver copper content. The hepatic metallothionein levels in female fish began to increase at the onset of exogenous vitellogenesis. Maximum levels were reached after estradiol-17beta and LSI levels had dropped in January. In male fish no distinct peaks in either zinc or copper levels were observed. The metallothionein levels increased somewhat during the time of spermatogenesis. It is suggested that metallothionein may regulate the hepatic zinc distribution during the annual reproductive cycle in female rainbow trout, thereby ensuring the organism of a control mechanism to keep the pool of available zinc at an appropriate level. PMID- 24233252 TI - Gonadotropin-induced changes in steroid production by ovaries of the common careCyprinus carnio L. around the time of ovulation. AB - Ovarian fragments from both primed (gonadotrophin treated) and unprimed female carp were incubated either with or without carp hypophysial homogenate and steroid hormone production measured. In incubations without hypophysial homogenate, production of all the steroids measured was either very low or nondetectable and there was no significant difference between tissue from primed and unprimed fish. In the presence of carp hypophysial homogenate a very significant increase in production of testosterone, 17-hydroxyprogesterone and testosterone glucuronide was observed, but there was no significant difference between primed and unprimed fish. 17,20beta-Dihydroxy-4-pregnen-3-one (17,20betaP) was not stimulated by carp hypophysial homogenatein vitro in ovaries from unprimed fish, but a very significant increase in production of this hormone was observed in tissue from fish which had received a priming dose of pituitary hormone. It is suggested that the priming dose of pituitary extract used in the normal hypophysation procedure to induce ovulation in teleosts initiates the potential for synthesis of 17,20betaP in response to later gonadotrophin challenge, and that this initiation may be related to the migration of the germinal vesicle. PMID- 24233253 TI - Stereoselective formation of amines by nucleophilic addition to azomethine derivatives. AB - This chapter describes state-of-the-art methods to prepare alpha-chiral amines by the addition of nonstabilized nucleophiles to imine derivatives. The first part of the chapter illustrates the most effective diastereoselective addition reaction (substrate controlled and chiral auxiliary based methods) whereas the second part focuses on catalytic asymmetric methods. PMID- 24233254 TI - Adherence to oral diabetes medications among users and nonusers of antipsychotic medication. AB - OBJECTIVE: This study compared adherence to oral diabetes medications among users and nonusers of oral antipsychotic medications. Adherence to oral antidiabetics and antipsychotics among antipsychotic users was also compared. METHODS: Texas Medicaid prescription claims data from July 1, 2008, to December 31, 2011, were used to examine adherence to oral antidiabetics among users and nonusers of antipsychotics for 12 months after the first prescription for oral diabetes medication. Users and nonusers of antipsychotics were matched on the basis of their chronic disease score (CDS). Medication adherence was measured by proportion of days covered (PDC), and patients with a PDC value >=.80 were considered to be adherent. Bivariate and multivariate analyses were used to compare adherence between cohorts. RESULTS: A total of 1,821 patients from each group were matched. The mean PDC for oral antidiabetics was significantly higher among antipsychotic users (.63) than nonusers (.55) (p<.001). About 37% (N=678) of antipsychotic users and 24% (N=473) of nonusers were adherent to oral antidiabetics. After adjustment for age, gender, CDS, and number of prescriptions, antipsychotic users were 2.10 times more likely than nonusers to be adherent to oral antidiabetics (p<.001). Antipsychotic users had higher mean PDC values for antipsychotic medications than for oral antidiabetics (.78+/-.25 versus .63+/-.29, p<.001). CONCLUSIONS: Adherence to oral antidiabetics in the Texas Medicaid population was better among antipsychotic medication users than nonusers, but overall adherence was poor for both groups. Low adherence rates highlight the need for interventions to help improve medication management. PMID- 24233255 TI - Motilin and gastrin secretion and lipid profile in preterm neonates following prebiotics supplementation: a double-blind randomized controlled study. AB - BACKGROUND: Gut hormones play an important role in the adaptation of the immature neonatal gut, and their secretion may be modulated by prebiotics. Furthermore, prebiotics are well known for their hypolipidemic potentials. We tested the hypothesis that prebiotics could alter motilin and gastrin secretion and reduce lipids in healthy preterms. METHODS: A total of 167 newborns were randomized to either a prebiotics enriched formula containing dietary oligosaccharides (short chain galacto-oligo-saccharides/long-chain fructo-oligo-saccharides [scGOS/lcFOS]), at a concentration of 0.8 g/100 ml, or a common preterm formula. Day 1 and 16 basal motilin, gastrin concentrations, and lipids were evaluated together with growth parameters, gastric residue, bowel habits, and feeding tolerance. Adverse events including necrotizing enterocolitis (NEC) and septicemia were also recorded. RESULTS: Mean motilin increase and day 16 mean values were greater for the intervention, compared with the control group (P = .001, P = .005, respectively), while gastrin remained high in both groups. Mean cholesterol and low density lipoprotein (LDL) increase were significantly greater in the control, compared with the intervention (P = .037, and P = .001) group. Day 16 LDL levels were significantly higher in the control group. Mean weight was increased in the control group, while gastric residue was less and stool frequency was increased in the intervention group. NEC and septicemia were not statistically different between groups. CONCLUSION: A prebiotics enriched formula resulted in significant surge of motilin relating to reduced gastric residue, compared with a common preterm formula. Mean cholesterol change was lower, while LDL was not increased in the prebiotics group, compared with the control group. PMID- 24233256 TI - Healthy subjects experience bowel changes on enteral diets: addition of a fiber blend attenuates stool weight and gut bacteria decreases without changes in gas. AB - BACKGROUND: Tube-fed patients frequently suffer from abnormal bowel function that affects intestinal bacteria and quality of life. Dietary fiber affects laxation and can be fermented by gut bacteria to metabolites that influence gut health and fecal moisture. The aim of this study was to compare the effects of a fiber-blend fortified enteral formula (FB, 15 g/L), a fiber-free formula (FF), and habitual diet on bowel function, fecal bacteria, and quality of life. MATERIALS AND METHODS: In a randomized, double-blind, crossover design, 20 healthy subjects consumed both FF and FB for 14 days with a 4-week washout. A 5-day fecal collection was used to assess stool output, whole-gut transit time (WGTT), total bacteria, bifidobacteria, lactobacilli, clostridia, and bacteroides. Subject gastrointestinal quality of life index (GIQLI) and side effects were also measured. RESULTS: On formula diets, 5-day fecal output decreased by >55% from habitual diet, but was 38% higher on FB than FF (P = .0321). WGTT was approximately 1.5 times longer on formula diets than habitual diet (P < .0004). Total bacteria declined from habitual diet on FF (P < .004), but not on FB. Numbers of bifidobacteria and lactobacilli declined from habitual diet on both formula diets, but bifidobacteria was higher on FB compared with FF (P < .0001). Bacteroides and clostridia numbers did not change between diets. GIQLI and incidence of gas symptoms did not differ between formulas. CONCLUSIONS: Addition of a fiber blend moderated changes in bowel function and gut bacteria observed in healthy subjects consuming FF. These results support adding mixed fiber sources to enteral nutrition if no contraindication exists. PMID- 24233258 TI - Early promising results for the endoscopic surgical treatment of Cushing's disease. AB - High levels of endogenous cortisol due to Cushing's disease cause significant mortality and morbidity. Treatment of Cushing's disease is challenging. For many years, transsphenoidal microsurgical resection of the adenoma has been the treatment of choice. However, recently, neuroendoscope has taken its place in the neurosurgeon's armamentarium, and the endoscopic transsphenoidal resection of pituitary tumors has become a familiar approach. Our aim was to present the results of pure endoscopic surgery in the treatment of corticotropinomas for comparison with the results of previous endoscopic and microsurgical series. We present a retrospective analysis of 90 patients with diagnosis of Cushing's disease who were operated between 2006 and 2012. Among 90 patients, a total of 81 (90.0 %) had a remission (28 out of 29 macroadenomas (96.6 %) and 53 out of 61 microadenoma patients (86.9 %)). Of note is that 66 out of 69 (95.7 %) primary patients (i.e., those who were operated in our center) and 15 out of 21 (71.4 %) patients previously operated in other centers reached a hypo/eucortisolemic state. A remission rate comparable with previous endoscopic series was achieved. In nine patients, it was not possible to achieve remission at all. On the other hand, only four of our cases (5.6 %) had a recurrence, and with reoperation, all of these patients entered a re-remission. To our knowledge, our series is the largest series studying endoscopically operated adrenocorticotropic hormone secreting adenomas. Our results suggest that the endoscopic approach has opened a new avenue in the treatment of Cushing's disease, previously a therapeutic challenge for both the clinician and the neurosurgeon. Endoscopic approach in the treatment of Cushing's disease is clearly better for patients because of its low morbidity rates and short duration of hospital stay. On the other hand, long-term follow-up of our patients will show whether these favorable observations will persist. PMID- 24233257 TI - Imaging changes following stereotactic radiosurgery for metastatic intracranial tumors: differentiating pseudoprogression from tumor progression and its effect on clinical practice. AB - Stereotactic radiosurgery has become standard adjuvant treatment for patients with metastatic intracranial lesions. There has been a growing appreciation for benign imaging changes following radiation that are difficult to distinguish from true tumor progression. These imaging changes, termed pseudoprogression, carry significant implications for patient management. In this review, we discuss the current understanding of pseudoprogression in metastatic brain lesions, research to differentiate pseudoprogression from true progression, and clinical implications of pseudoprogression on treatment decisions. PMID- 24233259 TI - Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older. AB - To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated. From 1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima- and Hiroshima University hospitals in Japan. Ten (1.1%) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients. The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2-3 on American Society of Anesthesiologists' Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered. Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients' general condition is well preserved and pituitary hormonal deficiency is adequately replaced. PMID- 24233260 TI - Feasibility of cervical intramedullary diffuse glioma resection using intraoperative magnetic resonance imaging. AB - Intraoperative magnetic resonance imaging (iopMRI) actually has an important role in the surgery of brain tumors, especially gliomas and pituitary adenomas. The aim of our work was to describe the advantages and drawbacks of this tool for the surgical treatment of cervical intramedullary gliomas. We describe two explicative cases including the setup, positioning, and the complete workflow of the surgical approach with intraoperative imaging. Even if the configuration of iopMRI equipment was originally designed for cranial surgery, we have demonstrated the feasibility of cervical intramedullary glioma resection with the aid of high-field iopMRI. This tool was extremely useful to evaluate the extent of tumor removal and to obtain a higher resection rate, but still need some enhancement in the configuration of the headrest coil and surgical table to allow better patient positioning. PMID- 24233261 TI - Using the comet assay to assess the combined and separate genotoxic effects of Cd and Zn in Eisenia andrei (Oligochaeta) at different temperatures. AB - Using the comet assay, the genotoxicity of Cd, Zn and Cd/Zn mixtures in Eisenia andrei was assessed after 4 weeks of exposure at 15, 20 and 25 degrees C. Relative to the controls, significant increases in TDNA% were observed in exposures to Cd alone at 500 and 1,000 mg/kg soil at both 20 and 25 degrees C, while a general decrease occurred at 15 degrees C. For Zn alone, a decreasing trend in TDNA% occurred at all three temperatures with increasing Zn concentration. For the Cd/Zn mixtures at 15 degrees C, genotoxicity was reduced at all mixture concentrations relative to the control. At 20 degrees C, the genotoxic response was similar to the control at all exposures. At 25 degrees C, the response was elevated at the 50 + 50 and 250 + 250 mg/kg mixture concentrations. In the remaining treatments at 25 degrees C, TDNA% was similar to the values in the respective control. The lack of consistently significant mixture genotoxicity may indicate antagonistic interactions between Cd and Zn in the mixtures. However, this was not conclusively determined because temperature alone had an inconsistent effect upon TDNA% readings in the control exposures. PMID- 24233262 TI - Clinical and genetic profile of children with periodic fever syndromes from a single medical center in South East Michigan. AB - OBJECTIVE: To report a cohort of children with periodic fever syndromes (PFS) from Southeast Michigan. METHODS: A retrospective review of medical records for patients referred for periodic fever over 5 years. RESULTS: Sixty-six patients including 21 FMF, 15 PFAPA, four TRAPS and one patient with combined HIDS and FMF were included. In addition, 25 patients were categorized as clinical PFS (cPFS) based on their clinical features however their genetic workup was either negative or inconclusive. Majority of the patients with FMF were from Middle Eastern background (88 %), but positive family history was noted in only 55 % of cases. Mean age at diagnosis was 40.8 months with a mean delay in diagnosis of 24 months. Most common MEFV mutations were p.M694V and p.M694I. Four patients with TRAPS were from mixed European descent and age at onset of symptoms was 6, 12, 12, and 84 months respectively. TNFRSF1A sequence variants in the TRAPS patients included p.R121Q (R92Q) and p.C99G (C70G); one patient had a rare occurrence of a concurrent p.V726A/-MEFV mutation. One patient with HIDS and FMF presented with atypical overlapping PFS clinical manifestations and genetic evaluation showed a unique combination of p.I268T/p.V377I MVK mutations and p.E230K/-MEFV variant. All patients with PFAPA group were from mixed European descent, symptoms started at a mean age of 34.6 months with a mean delay in diagnosis of 23.3 months. Symptoms started during infancy in six patients. All patients fulfilled the diagnostic criteria for PFAPA. The mean age of onset of symptoms in cPFS group was 17.2 months. Empiric colchicine and glucocorticosteroids controlled flares in majority of patients with cPFS. No evidence of amyloidosis was found in this entire cohort of 66 patients after a mean of 29.2 months of follow-up. CONCLUSION: PFS can present with atypical manifestations and should not be excluded based on a negative family history. Concomitant mutations in different autoinflammatory disorders genes can be present and possibly explain atypical manifestations. Various therapies may be considered even if genetic testing is inconclusive or negative. PMID- 24233263 TI - Terminal deletion of 11q with significant late-onset combined immune deficiency. AB - PURPOSE: We report a 45-year old female adult patient with terminal deletion of chromosome 11q resulting in clinical phenotype of late-onset combined immunodeficiency. METHODS: We describe the clinical phenotype and discuss the similarities between our patient and those with chromosome 22q11.2 deletion syndrome. Immunological evaluation included immunoglobulin levels, vaccine responses, number and function of T, NK and B cell subsets and comparative genomic hybridization test of blood and fibroblasts. RESULTS: The patient suffered from recurrent pneumococcal pneumonia and genital and cutaneous condylomas. She had a history of learning difficulties, dysmorphic features, autoimmune thyroiditis, chronic thrombocytopenia and severe asthma. We found Paris-Trousseau type thrombocytopenia, B-, T- and NK-lymphopenia, T cell oligoclonality and IgG hypogammaglobulinemia with inability to respond to pneumococcal polysaccharide, tetanus and diphtheria vaccines. A terminal deletion of chromosome 11q compatible with partial Jacobsen syndrome was found. CONCLUSIONS: This confirms Jacobsen syndrome as a chromosome deletion syndrome able to cause combined immunodeficiency. PMID- 24233264 TI - Regeneration of haploid and dihaploid plants from protoplasts of supersweet (sh2sh2) corn. AB - Plants were regenerated from maize (Zea mays L.) protoplasts isolated from embryogenic cell suspensions. The donor maize suspension cultures were established from friable callus initiated from microspores of a commercial supersweet hybrid (sh2sh2). The frequency of cell colony formation was higher when protoplasts were cultured on feeder layers of maize cells as compared with a liquid thin layer method. It was demonstrated that haploid and dihaploid soil grown plants can be regenerated from maize protoplasts isolated from haploid cell cultures. PMID- 24233265 TI - Selection of bacterial wilt-resistant tomato through tissue culture. AB - Bacterial wilt-resistant plants were obtained using a tomato tissue culture system. A virulent strain ofPseudomonas solanacearum secreted some toxic substances into the culture medium. Leaf explant-derived callus tissues which were resistant to these toxic substances in the culture filtrate were selectedin vitro and regenerated into plants. These plants expressed bacterial wilt resistance at the early infection stage to suppress or delay the growth of the inoculated bacteria. On the other hand, complete resistance was obtained in self pollinated progeny of regenerants derived from non-selected callus tissues. These plants showed a high resistance when inoculated with this strain, and were also resistant when planted in a field infested with a different strain of the pathogen. PMID- 24233266 TI - Transformation of pea (Pisum sativum L.) byAgrobacterium tumefaciens. AB - Explants fromPisum sativum shoot cultures and epicotyls were transformed by cocultivation withAgrobacterium tumefaciens vectors carrying plant selectable markers and transformants could be selected on a medium containing kanamycin. Transformants could also be obtained at a low frequency by cocultivating small protoplast-derived colonies. The transformed nature of the calli obtained from selection was confirmed by opine assay and DNA analysis. In addition five cultivars of pea were tested for their response to seven differentAgrobacterium tumefaciens strains. The response pattern coincided largely between the different pea cultivars, being more dependent on the bacterial strain than the cultivar used. PMID- 24233267 TI - The use of in vitro-grown microtuber discs inAgrobacterium-mediated transformation of Russet Burbank and Lemhi Russet potatoes. AB - We have usedin vitro-grown microtuber discs in the transformation of Russet Burbank and Lemhi Russet potato (Solanum tuberosum L.) cultivars byAgrobacterium mediated gene transfer. Transformed plants were selected by their resistance to kanamycin and identified by beta-glucuronidase activity. Northern blot analysis confirmed the presence of the corresponding messenger RNA. The ability to transform these two cultivars promises significant improvements to agronomically important varieties. PMID- 24233268 TI - Plant regeneration from protoplasts of Indica type rice and CMS rice. AB - Cell suspensions were established from 12 rice genotypes including Indica type, Japonica type and cytoplasmic male sterile (cms) rice lines of both types. 133 green plants were regenerated from protoplasts isolated from an Indica type rice and 15 plants were obtained from a Japonica type cms rice. A cell suspension, from which protoplasts can be isolated (about 10(6)/ml) but from which cell division has not yet been induced, has been established from the most widely used Indica type cms rice which contains Wild Abortive (WA) cytoplasm. PMID- 24233269 TI - Regulation of cell proliferation and morphogenesis by amino acids inBrassica tissue cultures and its correlation with threonine deaminase. AB - The effect of amino acids has been investigated with respect to the capacity ofBrassica cultures to undergo proliferation and differentiation. Hormone medium without any amino acid resulted in 6% shoot formation. Addition of optimal concentrations of L-leucine and L-isoleucine enhanced shoot formation upto 30% and 60%, respectively. L-methionine, L-threonine and pyruvic acid supported only proliferation but no differentiation. Amino acids had a marked effect on the activity of enzyme threonine deaminase (TD), bothin vivo andin vitro. TD in proliferating callus cultures was 3-fold higher than in differentiating cultures. Amino acids which induced cell proliferation increased TD while those which supported differentiation repressed it. Amino acids which did not alter TD activity had no effect on morphogenesis. The results suggest that amino acids play a regulatory role inBrassica morphogenesis which can be correlated with the activity of threonine deaminase. PMID- 24233270 TI - High frequency transformation ofKalanchoe laciniata. AB - Leaf explants ofKalanchoe laciniata were cocultivated for different days (2, 4, 6 and 8 days) with disarmedAgrobacterium tumefaciens strains A208SE, GV3111SE and EHA101 carring a binary vector pROA93. The vector contains a cauliflower mosaic virus 35S promotor which drives the coding sequence of neomycin phosphotransferase II (NPT-II) in one direction and beta-glucuronidase (GUS) in the opposite direction. Prolonged cocultivation (6 days) resulted in a marked increase of GUS gene transient expression, in terms of, the number of explants with transformed cells (up to 100%) and the percent area of transformed tissue (~ 50%). Explants cocultivated for 6-7 days showed a dramatic increase in the frequency of stable transformation and 75-80% of the inoculated explants produced transgenic plants. Cocultivation with the nopaline strain A208SE for 7 days gave as high as 10 transgenic plants per explant. PMID- 24233271 TI - Efficient transformation with regeneration of the tropical pasture legumeStylosanthes humilis usingAgrobacterium rhizogenes and a Ti plasmid-binary vector system. AB - Agrobacterium rhizogenes carrying the binary Ti plasmid vector pGA492 was used to transform leaf and stem explants of the tropical pasture legumeStylosanthes humilis. Conditions which yielded kanamycin resistant roots at a frequency of up to 86% and subsequent plant regeneration at a frequency of 23% were defined. Transgenic plants were fertile and either grew normally or had stunted growth but otherwise showed only minor morphological abnormalities. Transgenic plants with normal phenotypes were obtained in the progeny of the primary regenerants. The presence of active neomycin phosphotransferase enzyme activity and binary vector DNA and TL-DNA was demonstrated in the regenerated plants. Evidence for the independent transfer of binary vector and TL-DNA was also obtained. This high frequency production of transgenic plants ofS. humilis is a major improvement over previous methods using disarmed strains ofA. tumefaciens as helper. PMID- 24233272 TI - Gallotannin production in cell cultures ofCornus officinalis Sieb. et Zucc. AB - Gallotannin mixtures composed of tri-, tetra- and pentagalloylglucoses were produced by callus and suspension cultures ofCornus officinalis Sieb. et Zucc. The content of the main tannin, 1,2,3,6-tetragalloylglucose, was 36 times that of the intact fruits. The other three tannins, 1,2,6-trigalloyl-glucose, 1,2,3,4,6 pentagalloyl-glucose, and 6-digalloyl-1,2,3-trigalloyl-glucose, were isolated and identified with the authentic specimens. The ratios of the amounts among these tannins were not changed much during the culture period, and by the differences in the combination of plant growth regulators in the medium. Tannin production was stimulated by 6-benzyladenine, whereas cell growth required 2,4 dichlorophenoxyacetic acid or 1-naphthaleneacetic acid. Light irradiation appears to have inhibited tannin production in the cell cultures. PMID- 24233273 TI - Increased induction of regenerable callus cultures from cultured kernels of the maize inbred FR27rhm. AB - Kernels of the maize inbred FR27rhm were cultured on various media to determine if the treatments would alter the frequency of formation of regenerable callus (induction frequency) by embryos excised from the kernels when they were placed on callus induction medium. The addition of 60 MUM dicamba (3,6-dichloro-o-anisic acid) to the kernel culture medium resulted in an induction frequency of 27-38% compared to 0% for controls on standard kernel culture medium. Embryos excised from dicamba-treated kernels also showed in-ovule callus-like tissue proliferation. The increased induction frequency and the callus-like tissue proliferation could also be produced by injecting the ears of field grown FR27rhm plants, 3-d post pollination, with 1.08 MUmoles of dicamba. The results indicate that treatment of the developing ear with dicamba, in vivo or the developing kernel in vitro, may be an effective means to increase the frequency of regenerable callus induction from recalcitrant maize genotypes, such as the B73 derivative FR27rhm. PMID- 24233274 TI - Carrot (Daucus carota) hypocotyl transformation usingAgrobacterium tumefaciens. AB - Daucus carota hypocotyl sections were transformed withAgrobacterium tumefaciens LBA4404 containing CaMV 35S promoter, beta-glucuronidase coding sequence and the nopaline synthase (Nos) poly adenylation sequences in Bin 19. Sliced sterile seedling hypocotyl segments were preincubated for 2 days, co-cultivated withAgrobacterium for an additional 2 days, and then transferred to medium containing 100ug/ml of kanamycin and 400ug/ml carbenicillin. In 6 weeks kanamycin resistant calli were obtained in 5.8% of the explants from one variety. Calli were subcultured on solid medium, and in 4 weeks introduced into suspension culture. NPTII and Southern blot analysis confirmed that three selected lines were transformed with 1-3 copies of the GUSII construction. GUS activity in transformants was 5 to 250 fold over background. PMID- 24233275 TI - Vitrification and soluble carbohydrate levels inPetunia leaves as influenced by media gelrite and sucrose concentrations. AB - Normal nodal segments ofPetunia hybrida were grown on Murashige and Skoog salts containing varied levels of Gelrite and sucrose. Higher concentrations of Gelrite decreased vitrification while increased sucrose concentrations promoted vitrification. Leaves of vitreous plants had higher levels of reducing sugars and sucrose but lower or undetectable levels of inositol as compared to normal plants. Normal plants on medium void of inositol have the ability to synthesize inositol and maintain levels equal to that found in plants from inositol containing media. PMID- 24233276 TI - Energy-requiring uptake of protoberberine alkaloids by cultured cells ofThalictrum flavum. AB - Cultured cells ofThalictrum flavum take up berberine exogenously added to medium against the concentration gradient. This uptake was temperature-dependent and sensitive to plasma membrane-bound ATPase inhibitors such as sodium orthovanadate and diethylstilbestrol, indicating that the process is mediated by an energy requiring system. The time-course of pH-shift during berberine uptake suggests the participation of a berberine-proton antiport system in the berberine uptake by the cultured cells. In addition, the existence of a specific transport system was suggested by the competitive inhibition of berberine uptake by berberine analogues, coptisine and jatrorrhizine. PMID- 24233277 TI - Cell wall synthesis and salt (saline) sensitivity in cultured colt cherry (Prunus avium * pseudocerasus) protoplasts. AB - In order to investigate the cellular basis of salt tolerance, Colt cherry (Prunus avium *pseudocerasus) protoplasts from mesophyll tissues and root cell suspension cultures were cultured in the presence of NaCl, KCl or Na2SO4, at normalities of 25, 50, 100 or 200 mN for each salt and with or without 2,6-dichlorobenzonitrile, an inhibitor of cell wall synthesis. Results showed that the acquisition of salt tolerance was concomitant with the onset of cell wall regeneration, with protoplasts exhibiting a greater salt tolerance than cells. PMID- 24233278 TI - Relative regeneration proficiency ofArabidopsis thaliana ecotypes. AB - We have compared regeneration proficiency for cultured explants from different tissues of different ecotypes ofArabidopsis thaliana. Proficiency varies widely with both tissue and ecotype, and is highest when the flux of light during regeneration is low. Analysis of F1 hybrids suggests that high proficiency is dominant to low proficiency. PMID- 24233279 TI - Stable transformation of eggplant (Solanum melongena L.) by cocultivation of tissues withAgrobacterium tumefaciens carrying a binary plasmid vector. AB - Stable transformation of eggplant to kanamycin resistance was obtained by cocultivation of cotyledonary and young leaves with the hypervirulent, fully oncogenicAgrobacterium tumefaciens strain A281 carrying plasmid pGA472. No transformation was observed when using the disarmedA. tumefaciens LBA4404 strain carrying pGA472 or when using either strain for cocultivation with eggplant suspension cells.The NPTII enzyme and DNA dot blot assays performed on callus cells growing in the presence of kanamycin indicated both the presence and expression of the foreign gene. The highest proportion of transformed explants was obtained from intact cotyledonary leaf pieces while the highest NPTII enzyme specific activity was detected in callus cells originating from superficially wounded cotyledonary leaf pieces. Kanamycin-resistant plantlets were regenerated after six months in culture. PMID- 24233281 TI - Modulating guest binding in sulfonylcalixarene-based metal-organic supercontainers. AB - Metal-organic supercontainers (MOSCs) represent a new family of synthetic receptors derived from container precursors and featuring both endo and exo cavities. A neutral MOSC has been functionalized into an anionic container by incorporating sulfo groups. The anionic MOSC exhibits cavity-specific binding properties in both solid state and solution. PMID- 24233282 TI - Neurobehavioral functioning and survival following lung transplantation. AB - BACKGROUND: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. METHODS: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. RESULTS: One hundred eleven patients died over a mean follow-up of 10.8 years (SD=0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR]=1.09, P=.012) and memory performance (HR=1.11, P=.030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored>13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR=1.85 [95% CI, 1.04, 3.28], P=.036). CONCLUSIONS: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov. PMID- 24233285 TI - Worldwide populations of the aphid Aphis craccivora are infected with diverse facultative bacterial symbionts. AB - Facultative bacterial endosymbionts can play an important role in the evolutionary trajectory of their hosts. Aphids (Hemiptera: Aphididae) are infected with a wide variety of facultative endosymbionts that can confer ecologically relevant traits, which in turn may drive microevolutionary processes in a dynamic selective environment. However, relatively little is known about how symbiont diversity is structured in most aphid species. Here, we investigate facultative symbiont species richness and prevalence among world-wide populations of the cowpea aphid, Aphis craccivora Koch. We surveyed 44 populations of A. craccivora, and detected 11 strains of facultative symbiotic bacteria, representing six genera. There were two significant associations between facultative symbiont and aphid food plant: the symbiont Arsenophonus was found at high prevalence in A. craccivora populations collected from Robinia sp. (locust), whereas the symbiont Hamiltonella was almost exclusively found in A. craccivora populations from Medicago sativa (alfalfa). Aphids collected from these two food plants also had divergent mitochondrial haplotypes, potentially indicating the formation of specialized aphid lineages associated with food plant (host associated differentiation). The role of facultative symbionts in this process remains to be determined. Overall, observed facultative symbiont prevalence in A. craccivora was lower than that of some other well-studied aphids (e.g., Aphis fabae and Acyrthosiphon pisum), possibly as a consequence of A. craccivora's almost purely parthenogenetic life history. Finally, most (70 %) of the surveyed populations were polymorphic for facultative symbiont infection, indicating that even when symbiont prevalence is relatively low, symbiont-associated phenotypic variation may allow population-level evolutionary responses to local selection. PMID- 24233286 TI - UV-induced effects on growth, photosynthetic performance and sunscreen contents in different populations of the green alga Klebsormidium fluitans (Streptophyta) from alpine soil crusts. AB - Members of the green algal genus Klebsormidium (Klebsormidiales, Streptophyta) are typical components of biological soil crust communities worldwide, which exert important ecological functions. Klebsormidium fluitans (F. Gay) Lokhorst was isolated from an aeroterrestrial biofilm as well as from four different biological soil crusts along an elevational gradient between 600 and 2350 m in the Tyrolean and South Tyrolean Alps (Austria, Italy), which are characterised by seasonally high solar radiation. Since the UVtolerance of Klebsormidium has not been studied in detail, an ecophysiological and biochemical study was applied. The effects of controlled artificial ultraviolet radiation (UVR; <9 W m(-2) UV-A, <0.5 W m(-2) UV-B) on growth, photosynthetic performance and the capability to synthesise mycosporine-like amino acids (MAAs) as potential sunscreen compounds were comparatively investigated to evaluate physiological plasticity and possible ecotypic differentiation within this Klebsormidium species. Already under control conditions, the isolates showed significantly different growth rates ranging from 0.42 to 0.74 MUm day(-1). The UVR effects on growth were isolate specific, with only two strains affected by the UV treatments. Although all photosynthetic and respiratory data indicated strain-specific differences under control conditions, UV-A and UV-B treatment led only to rather minor effects. All physiological results clearly point to a high UV tolerance in the K. fluitans strains studied, which can be explained by their biochemical capability to synthesize and accumulate a putative MAA after exposure to UV-A and UV-B. Using HPLC, a UV absorbing compound with an absorption maximum at 324 nm could be identified in all strains. The steady-state concentrations of this Klebsormidium MAA under control conditions ranged from 0.09 to 0.93 mg g(-1) dry weight (DW). While UV-A led to a slight stimulation of MAA accumulation, exposure to UV-B was accompanied by a strong but strain-specific increase of this compound (5.34-12.02 mg(-1) DW), thus supporting its function as UV sunscreen. Although ecotypic differences in the UVR response patterns of the five K. fluitans strains occurred, this did not correlate with the altitude of the respective sampling location. All data indicate a generally high UV tolerance which surely contributes to the aeroterrestrial lifestyle of K. fluitans in soil crusts of the alpine regions of the European Alps. PMID- 24233287 TI - Investigation of acetone-butanol-ethanol (ABE) fermentation by fluorescence. AB - Photophysical techniques have potential for the development of optical sensors in monitoring and controlling fermentors. In the particular case of acetone-butanol ethanol (ABE) fermentation, carried out by bacteria of the speciesClostridium acetobutylicum, we have developed two studies based on fluorescence spectroscopy. First, we measured the intrinsic fluorescence of NADH related to bacteria metabolism, leading to a linear relationship between the NADH specific fluorescence and the specific rate of butyric acid production. At the same time, we have correlated enzymatic activities (acetate kinase, butyrate kinase, acetoacetate decarboxylase) with NADH specific fluorescence. Second, we studied the fluorescence polarization of extrinsic DPH (1,6-diphenyl-1,3,5-hexatriene) related to membrane fluidity. A simultaneous increase in both DPH anisotropy (order parameter increase) and butanol production is observed. Even though these results seem contradictory, because of the well-known fluidizing effect of butanol on lipids, they can be explained by a homeoviscous response ofC. acetobutylicum to the presence of butanol during fermentation. Thus the apparent changes in fluidity could be the result of the adaptative membrane alteration. PMID- 24233288 TI - Fiber-optic fluorescing sensors for nitrate and nitrite detection. AB - Fiber-optic sensors allow remote analyses of chemical substances and they now find many applications in chemistry and biology [1,2]. The purpose of this short report is to give our first results in the development of optical-fiber chemical sensors. Among the numerous known spectrometric methods, we chose the fluorometric one, generally described as a suitable method for determining substances at the parts per million or parts per billion level, with the objective of analyzing nitrate and nitrite anions, using modifications of the fluorescence emission of suitable dyes. The detection of nitrates is based on the irreversible nitration of fluorescein, which leads to a subsequent inhibition of fluorescence emission [3]; determination of nitrites corresponds to their addition on 2,3-diaminonaphthalene, which on the contrary, improves the fluorescence emission [4]. To set up simple instrumentation, we are developing fiber-optic sensors. This consists of (i) realizing an extrinsic active optical fiber by chemical linkage of suitable fluorescent dyes on silica fiber involving silanization reaction (APTES) and chemical methods and (ii) designing an optical device which is appropriate for measurements with optical fibers. The threshold of detection, coating efficiency, and stability with time are presented. PMID- 24233289 TI - Environmentally shifted fluorescence lifetimes for multicomponent phase modulation fluorimetric analysis. AB - Several cyclodextrins, surfactants, and a series of three organic solvents methanol, isoamylic alcohol, and hexanol-with different polarities and viscosities, were used to study the influence of the microenvironment on the fluorescent behavior of three diuretics-furosemide, triamterene, and piretanide. We concluded that on going from methanol to hexanol, the fluorescence lifetime of furosemide from 0.91 to 2.10 ns, that of triamterene from 4.54 to 4.44 ns, and that of piretanide from 5.24 to 10.37 ns. At 40 MHz, the phase shifts (excitation/emission) produced by furosemide, triamterene, and piretanide were 12.0, 29.6, and 30.2 degrees in methanol and 27.8, 48.1, and 69.0 degrees in hexanol. A three-factor, three-level factorial design allowed us to establish a calibration matrix of the three diuretics that covered the three ranges from 10 to 40, 1.5 to 6, and 0.1 to 0.4 MUM for furosemide, piretanide, and triamterene, respectively. Data processing incorporated PLS adjustment values. The function was fitted to a phase-resolved fluorescence intensity at the three phase angles selected. Percentages recoveries were from 88 to 115%. PMID- 24233291 TI - Optical sensor for ammonia based on the inner filter effect of fluorescence. AB - A new indicator-immobilization technique for the development of a sensor material for monitoring ammonia gas in aqueous solutions in presented. It is based on the change in absorbance intensity of a lipophilized pH indicator homogeneously dissolved in silicone rubber. Exposure to ammonia leads to a deprotonation of the indicator and this increases the absorbance of the base form of the indicator bromophenol blue. The sensor responds over a 17 MUg/L to 17 mg/L concentration range, with a detection limit of 12 MUg/L. PMID- 24233292 TI - Optical determination of pH on surfaces using immobilized Fluorescent dyes. AB - The attachment of pH-sensitive Fluorescent dyes on to hydroxylapatite for measuring the pH of small volumes is described. Fluorescein and acridine were used, both activated with reactive functions, such as isothiocyanate or succinimidyl ester groups, to enhance the possibility of a covalent linkage to the surface. First investigations were carried out on synthetic hydroxylapatite as the surface material. After the preparation of a particular surface with the fluorescent dye, steady-state and time-resolved fluorescence spectroscopies were employed for estimating the pH value of a solution applied to the surface. In this paper we present the results of our investigations done with both methods. Fluorescein shows significant variation in excitation spectra with pH, whereas in the case of acridine, the fluorescence lifetimes are very sensitive to pH. PMID- 24233290 TI - Laser-induced autofluorescence for medical diagnosis. AB - The naturally occurring autofluorescence of cells and tissues is based on biomolecules containing intrinsic fluorophores, such as porphyrins, the amino acids tryptophan and tyrosine, and the coenzymes NADH, NADPH, and flavins. Coenzymes fluoresce in the blue/green spectral region (fluorecence lifetimes: 0.5 6 ns) and are highly sensitive indicators of metabolic function. Steadystate and time-resolved blue-green autofluorescence is, therefore, an appropriate measure of the function of the respiratory chain as well as of cellular and tissue damage. Autofluorescence in the yellow/red spectral region is based mainly on endogenous porphyrins and metalloporphyrins, such as coproporphyrin, protoporphyrin (fluorescence lifetime of porphyrin monomers: >10 ns), and Zn protoporphyrin (2 ns). Various pathological microorganisms such asPropionibacterium acnes, Pseudomonas aeruginosa, Actinomyces odontolyticus, Bacteroides intermedius, andSaccharomyces cerevisiae are able to synthesize large amounts of these fluorophores and can therefore be located. This permits fluorescence-based detection of a variety of diseases, including early-stage dental caries, dental plaque, acne vulgaris, otitis externa, and squamous cell carcinoma. The sensitivity of noninvasive autofluorescence diagnostics can be enhanced by time-gated fluorescence measurements using an appropriate time delay between ultrashort laser excitation and detection. For example, videocameras with ultrafast shutters, in the nanosecond region, can be used to create "caries images" of the teeth. Alternatively, autofluorescence can be enhanced by stimulating protoporphyrin biosynthesis with the exogenously administered porphyrin precursor 5-aminolevulinic acid (ALA). The fluorophore protoporphyrin IX (PP IX) is photolabile and photodynamically active. Irradiation of PP IX containing tissue results in cytotoxic reactions which correlate with modifications in fluorescence due to photobleaching and singlet oxygen-dependent photoproduct formation. Therefore, on-line autofluorescence measurements during the phototreatment can yield information on the efficiency of ALA-based photodynamic therapy. PMID- 24233293 TI - Delayed fluorescence of porphyrins in different media. AB - Lifetimes of TPPS4 (meso-tetraphenylporphine tetrasulfonate) triplet states were measured for liquid solutions of different acidity and viscosity and as a function of acceptor concentration for different acceptors (bovine serum albumin, tryptophan and furfuryl alcohol). Triplet lifetimes were estimated by monitoring the decay of TPPS4 delayed fluorescence of E-type. The lifetime of delayed fluorencence depends on the concentration of O2, since the latter is an effective quencher of the triplet state. The lifetime is shown to be influenced mainly by degree of aggregation state of TPPS4 and, therefore, by the pH of the solution, decreasing with pH and for each pH remaining constant over a wide range of acceptor concentrations. The monomeric species is found to have the longest triplet lifetime in aqueous phosphate-buffered saline solution at neutral pH, especially when bound to albumin, despite of the low viscosity and protonated nature of the medium. PMID- 24233294 TI - Influence of the N-alkyl chain length on the J-aggregation behavior of a cyanine dye. AB - A new series of benzimidocarbocyanine dyes having diffeerent N-alkyl chain lengths (C2-C12) but the same chromophoric system was synthesized to investigate the effect of the dye structure on the photophysical properties of J-aggregate forming dyes. For these dyes, the number of J-absorption band depends on the chain length of the alkyl substiuents, whereas the fluorescence emission spectra exhibit only a single J-band. Furthermore, an increase in the N-alkyl-chain length leads to a strong decrease in the bandwidth of the J-absorption and emission bands. PMID- 24233295 TI - Excition dynamics in the J-aggregates of a carbocyanine dye. AB - We report on the exciton dynamics in the J-aggregating dye 5,5', 6,6'-tetrachloro 1,1'-diethyl-3,3'-di(4-sulfobutyl)-benzimidazolocarbocyanine which is known readily to form J-aggregates, even at room temperature and at a low concentration. We performed a series of time-correlated singlephoton-counting experiments at different emission wavelengths and at different temperatures in the range between 1.5 and 125 K. Additionally, the temperature dependence of the relative fluorescence quantum yield was determined. PMID- 24233296 TI - Time-resolved fluorescence of crown ether styrul dyes. AB - Photophsical processes are studied in a new class of dyes contining a chromophoric part and a crown ether part. Fluorescence decays were oebserved to be strongly dependent on temperature in the range from 294 to 4 K. Photoinduced isomerization and electron transfer are considered as possible mechanisms to explain the results. PMID- 24233297 TI - Photochemical mechanisms producing large fluorescence stokes shifts. AB - Various adiabatic photochemical mechanisms are compared which lead to a product in the excited state and therefore often to strongly red-shifted fluorescence. The applicational aspects of this strong red shift are outlined with respect to scinitillators, solar collectors, and biological fluorescence probese. As an example, the unusual fluorecence properties of a pyrazalocoumarin derivative are described. PMID- 24233298 TI - Unusual fluorescence red shifts in (TICT)-forming boranes. AB - Pyrrole substituted mesitylboranes and benzonitriles show highly solvent sensitive forbidden emission. In twisted model compounds, both fluorescence red shift and forbiddenness are increased. PMID- 24233299 TI - Fluorescence ofp-N, N-dimethylaminobenzonitrile incorporated in pores of molecular sieves. AB - The donor-acceptor-substituted aromatic moleculep-N, N-dimethylaminobenzonitrile (DMABN) is known to show a characteristic dual twisted intramolecular charge transfer (TICT) fluorescence with a pronounced solvent dependence. Despite the two-band structure of the fluorescence from DMABN incorporated within pores of the molecular sieves AlPO-5, SAPO-5, ZSM-5, and silicalite, there is no indication for TICT-state emission. PMID- 24233300 TI - Quenching problems in inorganic luminescent materials. AB - Quenching problems were investigated on inorganic luminescent materials for fluorescent lamps. It could be shown that the decrease of luminescence intensity under the influence of short-wave UV radiation is not only a function of the irradiation time but also depends strongly on the activator concentration and a mechanical treatment. The photochemical luminescence quenching represented by the intensity loss as a function of the irradiation time can be expressed as a sum of three exponential terms, constants and exponents of which contain the concentration of virgin and UV induced lattice defects in both the bulk and the surface. To explain the complex quenching process the theory of radiationless energy transport was used. PMID- 24233301 TI - Determination of the directions of the transition dipoles in tetrabutylperylene in stretched polymers. AB - The directions of the transition dipole moments of 2,5,8,11,-tetra-butylperylene were determined from angle-resolved fluorescence depolarization experiments on molecules embedded in a stretched anhydrous nitrocellulose matrix. The absorption transition moments lies almost parallel to the elongated axis of the molecule, but the emission transition moment makes an angle of 20 degrees with the axis. The orientational distribution of the molecules in the polymer indicates significant deviations from a circular form. PMID- 24233302 TI - Spectro-streak picosecond studies of intramolecular charge-transfer fluorescence. AB - A spectro-streak photometer, an instrument for simultaneously measuring fluorescence intensity, time, and wavelength,I(t, lambda), with a single picosecond excitation pulse, has been constructed. Two typical and currently highly topical examples of mesurements are discussed. (1) the temporal development of the fluorescence form the intramolecular charge-transfer (ICT) state of the rigid aromatic compound 4,5-(1'-methylindolino)3,4-naphthanthracene is studied in the protic solvent hexanol. (2) Propyl chain-linked pyrene/N,N dimethylaniline is used as the model compound to study conformational changes associated with the transition from a contact ion pair to a sandwich exciplex. PMID- 24233303 TI - Multiplexed time-correlated single-photon counting. AB - We review the technique of multiplexed time-correlated single-photon counting whereby multiple fluorescence decay curves are recorded in parallel by statistically time-sharing a single time-to-amplitude converter. Application of the multiplexing technique to measuring the fluorescence lifetime topography of a self-absorbing sample is demonstrated. Further possibilities are discussed for multiplexed optical fiber sensor networks with built-in intelligence for detecting and discriminating between different metal ions in solution. PMID- 24233304 TI - Quenching of fluorescence by light: A new method to control the excited-state lifetimes and orientations of fluorophores. AB - We report steady-state and time-resolved studies of quenching of fluorescence by light i.e. "light quenching." The dyes rhodamine B (RhB) and 4-dicyanomethylene-2 methyl-6(p-dimethamino)-4H-pyrane (DCM) were excited in the anti-Stokes region from 560 to 615 nm. At a high illumination power the intensities of DCM and RhB were sublinear with incident power, an effect we believe is due to stimulated emission, andnot ground-state depopulation. The extent of light quenching was proportional to the amplitude of the emission spectrum at the incident wavelength, as expected for light-stimulated decay from the excited state. Control measurements at a decreased average illumination power, and in solvents of various viscosities, indicated that the effect was not due to undesired photochemical processes. Importantly, the frequency-domain intensity decays remained single exponentials, and the lifetimes were unchanged with light quenching, which suggests that the effect was not due to heating or other photochemical effects. These results are consistent with a quenching process which occurs within the quenching pulse. Importantly, as expected for light quenching with a single pulsed laser beam, the time 0 anisotropies of RhB and DCM were decreased due to orientation-dependent quenching of the excited-state population. In closing we discuss some possible future applications of light quenching to studies of dynamic processes. PMID- 24233305 TI - Simultaneous antigen detection using multiplex dyes. AB - To detect several antigens simultaneously, antibodies directed against different antigens were immobilized on a quartz surface. The antigens were tagged with multiplex, dyes, which show different fluorescence lifetimes but similar excitation and emission spectra. The antigens were detected by recognizing the characteristic fluorescence lifetime. Furthermore, the effect of labeling of the dye on the antigen molecules was examined. PMID- 24233306 TI - Emerging biomedical and advanced applications of time-resolved fluorescence spectroscopy. AB - Time-resolved fluorescence spectroscopy is presently regarded as a research tool in biochemistry, biophysics, and chemical physics. Advances in laser technology, the development of long-wavelength probes, and the use of lifetime-based methods, are resulting in the rapid migration of timeresolved fluorescence to the clinical chemistry lab, the patient's bedside, and even to the doctor's office and home health care. Additionally, time-resolved imaging is now a reality in fluorescence microscopy and will provide chemical imaging of a variety of intracellular analytes and/or cellular phenomena. Future horizons of state-of-the-art spectroscopy are also described. Two photon-induced fluorescence provides an increased information content to time-resolved data. Two photoninduced fluorescence, combined with fluorescence microscopy and time-resolved imaging, promises to provide detailed three-dimensional chemical imaging of cells. Additionally, it has recently been demonstrated that the pulses from modern picosecond lasers can be used to quench and/or modify the excited-state population by stimulated emission since the stimulated photons are directed along the quenching beam and are not observed. The phenomenon of light quenching should allow a new class of multipulse time-resolved fluorescence experiments, in which the excited-state population is modified by additional pulses to provide highly oriented systems. PMID- 24233307 TI - I. Past, present, and future of 'Do not attempt resuscitation' orders in the perioperative period. PMID- 24233308 TI - III. Oxygen therapy in anaesthesia: the yin and yang of O2. PMID- 24233309 TI - Functional magnetic resonance imaging in anaesthesia research. PMID- 24233310 TI - Awake insertion of the air-QTM intubating laryngeal airway device that facilitates safer tracheal intubation in morbidly obese patients. PMID- 24233311 TI - Bradycardia after dexamethasone for postoperative nausea and vomiting prophylaxis during induction of anaesthesia. PMID- 24233312 TI - Long-stay patients with cancer on the intensive care unit: characteristics, risk factors, and clinical outcomes. PMID- 24233313 TI - Key-ring data sheet to provide critical information required in managing paediatric emergencies. PMID- 24233314 TI - Knowledge related to anaesthesia among laypeople. PMID- 24233315 TI - Growing menace of ibogaine toxicity. PMID- 24233316 TI - Sustained effect of spinal cord stimulation on pain and quality of life in painful diabetic peripheral neuropathy. PMID- 24233317 TI - Early surgical reintervention for haemostasis after breast surgery using persistent sensory block of a paravertebral block. PMID- 24233318 TI - Ultrasound diagnosis of nasogastric tube misplacement into the trachea during bypass surgery. PMID- 24233319 TI - Planned magnetic resonance imaging for a patient with a permanent pacemaker in situ with suspected spontaneous intracranial hypotension. PMID- 24233320 TI - Sugammadex in a patient with Sjogren's syndrome and polymyositis. PMID- 24233327 TI - Enjoyment and emotionally negative reactions in minor-adult versus minor-peer and adult-adult first postpubescent coitus: A secondary analysis of the Kinsey data. AB - Using the original Kinsey sample, enjoyment and emotionally negative reactions to first postpubescent coitus were examined in relation to whether the coitus occurred as a legal minor (aged under 18) with an adult (5 or more years older), a minor with a peer (within 4 years of age), or an adult with an adult (both 18 or older). These responses were further examined in subdivisions of the minor adult and adult-adult categories. Given widely held professional and lay assumptions that minor-adult sex is intrinsically traumatic or aversive, tested was whether reactions to minor-adult coitus were characteristically negative, irrespective of gender, and distinctly more negative than minor-peer and adult adult coitus. In general: minors with adults enjoyed the event as much as minors with peers or adults with adults; boys (i.e., male minors) enjoyed it substantially more than girls, irrespective of partner age; and minors with adults did not have more emotionally negative reactions than the other groups. Younger boys (14 and under) with women (mean ages: 13.37 and 24.27, respectively; mean age difference: 10.90 years), compared to men with peer-aged women (mean ages: 21.76 and 21.58, respectively; mean age difference: 0.18 years), enjoyed the coitus a great deal (the top scale value) significantly more often (63 % vs. 44 %) and had emotionally negative reactions no more often (15 % vs. 12 %). Younger girls (14 and under) with men (mean ages: 13.19 and 26.42, respectively; mean age difference: 13.23 years), compared to women with peer-aged men (mean ages: 22.38 and 23.78, respectively; mean age difference: 1.41 years), enjoyed the coitus a great deal at the same rate (17 % vs. 18 %) and had emotionally negative reactions no more often (18 % vs. 16 %). Assumptions of characteristic trauma or aversiveness in minor-adult first coitus, as well as gender equivalence in response, were contradicted. PMID- 24233328 TI - Incorporating couples-based approaches into HIV prevention for gay and bisexual men: opportunities and challenges. AB - Thirty years after the beginning of the HIV epidemic, gay, bisexual, and other men who have sex with men (collectively called MSM) bear a disproportionate burden of HIV in the United States and continue to acquire a distressingly high number and proportion of new infections. Historically, HIV prevention for MSM has been focused on individual-level behavior change, rarely intervening with MSM as part of a couple. Yet, an estimated 33-67% of HIV infections among MSM are acquired from primary sexual partners, suggesting that work with MSM as couples could be an important contributor to prevention. Given the emergence of high impact combination HIV prevention, it is timely to consider how work with the broad variety of male couples can improve both personal and community health. Couples HIV testing and counseling for MSM is an important advance for identifying men who are unaware that they are HIV-positive, identifying HIV discordant couples, and supporting men who want to learn their HIV status with their partner. Once men know their HIV status, new advances in biomedical prevention, which can dramatically reduce risk of HIV transmission or acquisition, allow men to make prevention decisions that can protect themselves and their partners. This paper highlights the present-day challenges and benefits of using a couples-based approach with MSM in the era of combination prevention to increase knowledge of HIV status, increase identification of HIV discordant couples to improve targeting prevention services,and support mutual disclosure of HIV status. PMID- 24233330 TI - The Crisis in the lack of skilled workers worldwide: Its meaning for healthcare worldwide. PMID- 24233329 TI - Sexual risk for HIV among gay male couples: a longitudinal study of the impact of relationship dynamics. AB - While the relationship context itself is increasingly being examined to understand sexual risk behavior among gay male couples, few studies have examined relationship dynamics and HIV risk longitudinally. We aimed to investigate relationship dynamics and psychosocial predictors of unprotected anal intercourse (UAI) with outside partners of serodiscordant or unknown HIV serostatus (UAIOUT) over time as well as UAI with primary partner in serodiscordant couples (UAIPP). We recruited a sample of 566 ethnically diverse, seroconcordant and serodiscordant couples and interviewed them six times over the course of 3 years. The surveys encompassed relationship dynamics between the partners and sexual behavior with primary and outside partners. We fit generalized linear mixed models for both the UAI outcomes with time and relationship dynamics as predictors while controlling for relationship length. Analyses of the longitudinal data revealed that, in both categories of couples, those with higher levels of positive relationship dynamics (e.g., commitment, satisfaction) were less likely to engage in UAIOUT. Higher investment in sexual agreement and communication were among the factors that significantly predicted less UAIOUT for seroconcordant couples, but not for the serodiscordant couples. For serodiscordant couples, greater levels of attachment and intimacy were associated with greater odds of UAIPP while increased HIV-specific social support was associated with lower odds of UAIPP. These results underscore the importance of creating and tailoring interventions for gay couples that help maintain and strengthen positive relationship dynamics as they have the potential to produce significant changes in HIV risk behavior and thereby in HIV transmission. PMID- 24233331 TI - High-dose gentamicin in newborn infants: is it safe? AB - Dosing regimens often recommend lower gentamicin doses in neonates (3-5 mg/kg) than in older children (7 mg/kg or more) despite the higher volume of distribution in neonates. We studied an extended-interval high-dose (6 mg/kg) gentamicin regimen in a single tertiary neonatal unit from 2004-2012. During the first week of life, dosing interval was 24 h for term infants, 36 h for preterm infants with gestational age (GA) 29-36 weeks and 48 h for preterm infants with GA <29 weeks. After the first week of life, dosing interval was 24 h if corrected age (GA + postnatal age) >=29 weeks and 36 h if corrected age <29 weeks. Outcome measures were trough plasma concentration (TPC), ototoxicity and prescription errors. In 546 treatment episodes, TPC was measured prior to the third gentamicin dose. There were 37 episodes (6.7 %) of prescription errors, mainly a too long dosing interval. We included 509 treatment episodes (440 infants) in the final analysis. Mean (standard deviation) gentamicin TPC during the first week of life was 1.1 (0.5) mg/L and after the first week of life 0.8 (0.6) mg/L. In 31 (6 %) episodes, TPC was >=2.0 mg/L, predominantly among term infants with renal impairment. Thirty-eight patients failed the neonatal hearing screening, but only four of these 38 had permanent hearing loss. All four had a TPC <2.0 mg/L. Conclusions: This extended-interval high-dose gentamicin regimen was associated with low numbers of elevated TPCs, low numbers of prescription errors and no evidence for ototoxicity. PMID- 24233332 TI - Early treatment of a child with NAGS deficiency using N-carbamyl glutamate results in a normal neurological outcome. AB - Acute hyperammonemia has a variety of etiologies and clinical manifestations. If not treated early in neonates, it leads to irreversible brain damage or death. We present a 7-day-old female patient who was brought to the emergency department with drownsiness and vomiting. Metabolic work-up revealed a blood ammonia level of 290 MUmol/L (normal <100 MUmol/L in neonates) with a compensated respiratory alkalosis, normal glycaemia and lactate and absence of urinary ketones. Oral feeding was stopped, an infusion of 20 % glucose was started, and sodium benzoate and arginine hydrochloride were given. After a drop of ammonemia within 12 h of treatment, it started rising again. N-carbamylglutamate (NCG) was added resulting in a rapid normalisation of ammonemia. Feedings were progressively reintroduced, the ammonia levels remained low. The results of the metabolic work-up were compatible with carbamyl phosphate synthase 1 (CPS1) or N-acetyl glutamate synthase (NAGS) deficiency. Genetic analysis confirmed the latter diagnosis with a homozygous mutation c. 1450T > C (p.W484R) in exon 6 of the NAGS gene in the patient and a carrier state in both parents. At the age of 9 months, the child is growing well with normal neurological development, under treatment with NCG 100 mg/kg/day and a normal diet. Conclusion: This case highlights the importance of keeping a high index of suspicion and early testing for ammonia levels in neonates/children with unexplained encephalopathy. In neonates with congenital hyperammonemia, NCG should always be started together with the standard management of hyperammonemia until all laboratory investigations are complete or indicate another disease. PMID- 24233333 TI - Life-threatening QT prolongation in a boy with attention-deficit/hyperactivity disorder on atomoxetine. AB - As a noncentral nerve-stimulating agent blocking reuptake of noradrenalin, atomoxetine is used for treatment of attention-deficit/hyperactivity disorder (ADHD). Because it has less potential for addiction and abuse and improves core symptoms of ADHD, it is commonly prescribed in many children and adolescents internationally. Its common side effects include headache, abdominal pain, decreased appetite, and weight loss. In addition, cardiac effects such as tachycardia and hypertension have also been reported. In this case report, an 11 year-old Japanese boy with a past medical history of ADHD on atomoxetine for more than 2 years presented with a loss of consciousness. Initial electrocardiogram (ECG) showed significant QT prolongation, and 9 h later, it worsened, along with bradycardia, inversed T waves, and multiple premature ventricle contractions (PVCs). Transthoracic echocardiography showed akinesis with dilation and systolic ballooning of the left ventricle's (LV) apical segment (Takotsubo cardiomyopathy). At that point, bisoprolol and transcutaneous pacing were started. After 5 days, transcutaneous pacing was discontinued due to improvement in his cardiac rhythm. He continued to remain asymptomatic for the next year, while his QT interval returned to normal. Conclusion: This case report suggests a serious side effect of atomoxetine, and to avoid life-threatening cardiovascular events for children and adolescents with ADHD on atomoxetine, prior screening for cardiovascular conditions by ECG with close monitoring is necessary. PMID- 24233334 TI - A radioimmunoassay for N-terminal peptide of chum salmon proopiocortin. AB - A highly specific radioimmunoassay was developed for N-terminal peptide of salmonid proopiocortin using a guinea pig antiserum to the chum salmon peptide (sNPP 1). Since sNPP I has no tyrosine residue nor free N-terminal amino group, a mixture of minor components of sNPP 1, which have extensions of H-Val-LysGly- and H-Lys-Gly- at the N-terminus, were iodinated by the lactoperoxidase method after incorporation of 3-(phydroxyphenyl)-propionate to the terminal amino groups. Plasma and pituitary extracts of several salmonid species showed parallel displacement to the standard hormone. Samples from carp, goldfish, tilapia, and eel, as well as the plasma of hypophysectomized rainbow trout, showed no crossreactivity. Proopiocortin-related hormones isolated from the chum salmon pituitary, including melanotropins, endorphins, corticotropin-like intermediate lobe peptides, and gonadotropin and prolactin showed negligible cross-reactivity. NPP contents in the pars intermedia of rainbow trout and chum salmon were 10 to 15 times greater than those in the pars distalis. Plasma levels of NPP in the mature chum salmon caught in the bay were about 50ng/ml. Plasma NPP levels in the mature chum salmon of both sexes decreased after transfer from seawater to fresh water. Plasma cortisol showed a concomitant change with NPP, thus supporting previous findings that NPP modulates corticotropin action on the trout interrenal. PMID- 24233335 TI - Effect of thyroid-stimulating hormone on the physiology and morphology of the thyroid gland in coho salmon,Oncorhynchus kisutch. AB - Activity of the thyroid gland of the coho salmon,Oncorhynchus kisutch, was assessed by physiological, histological and ultrastructural criteria after treatment with graded doses of bovine thyrotropin (bTSH) in January and March. Average plasma thyroxine (T4) levels increased from about 0.8 ng/ml in saline injected controls to about 15 ng/ml in fish treated with four intraperitoneal injections of 0.8 lU bTSH. Light-microscope observations of one MUm-thick sections stained with methylene blue and azure II, showed that bTSH treatment increased epithelial height in both presmolts and smolts. Ultrastructural manifestations of increased activity owing to bTSH treatment were also seen, along with evidence of follicle proliferation. Cytoplasmic organelles and secretory granules increased in numbers with increased dosage of bTSH. PMID- 24233336 TI - Effects of thyroid hormone supplementation of canola meal-based diets on growth, and interrenal and thyroid gland physiology of rainbow trout (Salmo gairdneri). AB - Rainbow trout fed a 26% canola meal-based (CM) diet for 12 weeks at 15 degrees C exhibited reduced growth, lower feed conversion, enlarged thyroid glands and lower plasma thyroid hormone (TH) levels than comparable fish fed equinitrogenous, equicaloric soybean meal-based (SB) diets. Supplementation of the SB diets with either T4 (20 mg/kg) or T3 (10 or 20 mg/kg) had no effect on the growth rate, feed conversion and thyroid histology of the trout. However, plasma T4 levels weredepressed in trout fed the T4- and high T3-supplemented SB diets. In trout fed T4- and T3-supplemented CM diets the growth rates and feed conversion were not significantly different from those of the SB-fed groups. Moreover, in the T4-supplemented group, plasma T4 levels were in the normal range. However, thyroid enlargement was evident in all the CM-fed fish, and plasma T3 levels were markedly elevated in groups fed the T3-supplemented CM diets. The data suggest that antithyroid components in the CM diets inhibited TH synthesis (but not their release), and impaired TH clearance from the circulation. There were no significant differences in plasma cortisol levels in the 8 treatment groups, nor were there differences in the histological appearance of the interrenal gland. However, when the data from SB- and CM-fed fish were pooled, plasma cortisol levels in the SB-fed fish were significantly lower than in the CM-fed animals. Glucosinolates at a level of 164 mg/kg diet were toxic to young trout, but the effect was ameliorated by dietary TH supplementation. PMID- 24233337 TI - Effects of adrenaline on ionic equilibria in red blood cells of rainbow trout (Salmo gairdneri). AB - Effects of adrenaline on the equilibrium distributions of Na(+) , K(+) , H(+) , Cl(-) , and H2O across the cell membrane of rainbow trout (Salmo gairdneri) erythrocytes were determinedin vitro, as a function of P CO2 (1.76-7.77 torr). CO2-carrying capacity of the blood was also examined. Plasma catecholamine concentrations inunanaesthetized, unrestrained trout were 3.1 nM adrenaline and 1.2 nM noradrenaline. Elevation of the plasma adrenaline concentrationin vitro to 4.6 * 10(3) nM resulted in net gains of Na(+) , Cl(-) and H2O by red cells, a net loss of H(+) from red cells, and a pronounced red cell swelling. Adrenaline also reduced the CO2-carrying capacity of trout bloodin vitro. The magnitudes of these effects increased with PCO2 and, thus, were sensitive to blood HCO3 (-) concentrations. The distribution of K(+) between red cells and plasma was unaffected by adrenaline. Adrenergic-mediated ion movements and red cell swelling were sensitive to both propranolol and SITS. These results are consistent with the symport NaCl uptake model for adrenergic-mediated swelling of Baroinet al. (1984). The adrenergic response of fish erythrocytes may function to ameliorate the effects of blood acidoses on O2-carrying capacity by maintaining red cell pH in the face of a decrease in plasma pH. PMID- 24233338 TI - Characterization of angiotensin-converting enzyme in the gills of rainbow trout,Salmo gairdneri (Richardson). AB - Several physical and chemical parameters of angiotensin-converting enzyme (ACE) were determined using a spectrophotometric assay of gill tissue homogenates from rainbow trout. This assay is based on the evolution of free hippuric acid via enzymatic cleavage of histidyl-leucine from the synthetic substrate hippuryl-l histidyl-l-leucine (HHL). Piscine ACE exhibited enzymatic and kinetic properties similar to those reported for the partially purified mammalian enzyme. Proteolytic activity was both temperature and pH dependent and demonstrated hyperbolic kinetics with an apparent Km of 2.5 mM. Hydrolysis of HHL was activated by Cl(-) at concentrations between 20 mM and 100 mM. Captopril (1 * 10( 6) M) and MK-422 (1 * 10(-6) M) blocked trout gill ACE activity, however, EDTA was inhibitory only at high concentrations (1 * 10(-3) M). These results demonstrate that trout ACE is functionally similar to mammalian ACE and that the spectro-photometric assay for ACE developed by Cushman and Cheung can be applied to analysis of converting enzyme activity in fish tissue homogenates. PMID- 24233339 TI - Drinking activity of the newly hatched larvae of codGadus morhua L. AB - The drinking rate of cod larvae 1-7 days post hatching was measured from the uptake of(3)H-labelled dextran (MW = 70000) admixed in the incubation seawater (34 ppt 5 degrees C). The drinking rate increased gradually from 0.15% to 0.59% of the larval body weight on day 1 and day 7 respectively. This increase in drinking rate correlated with an observed decrease in the volume of the yolk sac and its water store. Autoradiographs showed the labelled dextran to be confined to the intestine. Electron micrographs showed an open mouth communicating with the oesophagus and the intestine in cod larvae at the time of hatching. Chloride cells were present on the opercular folds but not on the vestigial, developing gills. The data indicate that the water acquisition mechanism of larval cod is similar to that of adult marine fish. PMID- 24233340 TI - Relationship between body mass index and the incidence of inguinal hernia repairs: a population-based study in Olmsted County, MN. AB - PURPOSE: The relationship between body mass index (BMI) and the risk of inguinal hernia development is unclear. To explore the relationship, we determined whether the incidence of inguinal hernia repairs (IHR) varied across patients with different BMI categories. STUDY DESIGN: A population-based incidence study was undertaken. We reviewed all IHR performed on adult residents of Olmsted County, MN from 2004 to 2008. Cases were ascertained through the Rochester Epidemiology Project, a records-linkage system with more than 97% population coverage. RESULTS: During the study period, a total of 1,168 IHR were performed on 879 men and 107 women. The median BMI of the cohort was 26.7 kg/m2 (range 14.9-58.1, interquartile range 23.9-28.9). Incidence rates varied significantly as a function of BMI (p<0.001). Rates were highest among men who were either normal weight or overweight (419.8 and 421.1 per 100,000 person-years for BMI<25 and BMI 25-29.9, respectively), and lowest for obese and morbidly obese men (273.5 and 99.4 per 100,000 person-years for BMI 30-34.9 and BMI C 35, respectively). Findings were similar across all age categories and in patients who had an IHR that was initial or recurrent, direct or indirect, and unilateral or bilateral. CONCLUSIONS: The incidence of IHR decreased as BMI increased. Obese and morbidly obese patients had a lower incidence of IHR than those who were normal weight or overweight. The causal mechanisms leading to such a relationship are unclear and warrant further study. PMID- 24233342 TI - Identification and characterization of agonist epitopes of the MUC1-C oncoprotein. AB - The MUC1 tumor-associated antigen is overexpressed in the majority of human carcinomas and several hematologic malignancies. Much attention has been paid to the hypoglycosylated variable number of tandem repeats (VNTR) region of the N terminus of MUC1 as a vaccine target, and recombinant viral vector vaccines are also being evaluated that express the entire MUC1 transgene. While previous studies have described MUC1 as a tumor-associated tissue differentiation antigen, studies have now determined that the C-terminus of MUC1 (MUC1-C) is an oncoprotein, and its expression is an indication of poor prognosis in numerous tumor types. We report here the identification of nine potential CD8+ cytotoxic T lymphocyte epitopes of MUC1, seven in the C-terminus and two in the VNTR region, and have identified enhancer agonist peptides for each of these epitopes. These epitopes span HLA-A2, HLA-A3, and HLA-A24 major histocompatibility complex (MHC) class I alleles, which encompass the majority of the population. The agonist peptides, compared to the native peptides, more efficiently (a) generate T-cell lines from the peripheral blood mononuclear cells of cancer patients, (b) enhance the production of IFN-gamma by peptide-activated human T cells, and (c) lyse human tumor cell targets in an MHC-restricted manner. The agonist epitopes described here can be incorporated into various vaccine platforms and for the ex vivo generation of human T cells. These studies provide the rationale for the T cell-mediated targeting of the oncogenic MUC1-C, which has been shown to be an important factor in both drug resistance and poor prognosis for numerous tumor types. PMID- 24233343 TI - The long-term immune response after HPV16 peptide vaccination in women with low grade pre-malignant disorders of the uterine cervix: a placebo-controlled phase II study. AB - The capacity of a low-dose HPV16 synthetic long-peptide vaccine (HPV16-SLP) to induce an HPV16-specific T-cell response as well as to establish long-term immunologic memory in patients with low-grade abnormalities of the cervix was determined in a placebo-controlled, double-blinded phase II study. In addition, the effect of a booster vaccination after 1 year was evaluated. Patients received either the HPV16-SLP or a placebo at the start of the study. After 1 year, the vaccinated patients were again randomized to receive the HPV16-SLP or a placebo. Patients were followed for 2 years. HPV16-specific T-cell responses were determined in pre- and post-vaccination blood samples by ELISPOT, proliferation assay and cytokine assays. We show that the HPV16-specific T-cell responses detected after vaccination are clearly due to vaccination and that reactivity was maintained for at least 2 years. Interestingly, a booster vaccination after 1 year especially augmented the HPV16-specific Th2 response. Furthermore, pre existing immunity to HPV16 was associated with a stronger response to vaccination and with more side effects, reflected by flu-like symptoms. We conclude that two low-dose injections of HPV16-SLP can induce a strong and stable HPV16-specific T cell response that lasts for at least 1 year. If booster vaccination is required, then polarizing adjuvant should be added to maintain the Th1 focus of the vaccine induced T-cell response. PMID- 24233344 TI - Selecting and measuring optimal outcomes for randomised controlled trials in surgery. AB - BACKGROUND: Randomised controlled trials (RCTs) in surgery are complex to design and conduct and face unique challenges compared to trials in other specialties. The appropriate selection, measurement and reporting of outcomes are one aspect that requires attention. Outcomes in surgical RCTs are often ill-defined, inconsistent and at high risk of bias in their assessment and historically, there has been an undue focus on short-term outcomes and adverse events meaning the value of trial results for clinical practice and decision-making is limited. PURPOSE: This review addresses three key problems with surgical trial outcomes choosing the right outcomes for the trial design and purpose, selecting relevant outcomes to measure from the range of possible outcomes, and measuring outcomes with minimal risk of bias. Each obstacle is discussed in turn, highlighting some suggested solutions and current initiatives working towards improvements in these areas. Some examples of good practice in this field are also discussed. CONCLUSIONS: Many of the historical problems with surgical trial outcomes may be overcome with an increased understanding of the trial design and purpose and recognition that pragmatic trials require assessments of outcomes that are patient-centred in addition to measurement of short-term outcomes. The use of core outcome sets developed for specific surgical interventions and the application of novel methods to blind outcome assessors will also improve outcome measurement and reporting. It is recommended that surgeons work together with trial methodologists to integrate these approaches into RCTs in surgery. This will facilitate the appropriate evaluation of surgical interventions with informative outcomes so that results from trials can be useful for clinical practice. PMID- 24233347 TI - Geographic and clinical variation in clozapine use in the United States. AB - OBJECTIVE: Antipsychotic medications are largely ineffective for approximately 30% of patients with schizophrenia that is considered "treatment resistant." Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but it is rarely used. This nationwide study examined predictors of clozapine use to help identify ways to optimize its use. METHODS: A retrospective study using U.S. Medicaid claims data from 45 states was conducted among 326,119 individuals with a schizophrenia spectrum disorder (ICD-9-CM code 295.X) who initiated one or more antipsychotic treatment episodes between January 2002 and December 2005. Multivariable logistic regression models were used to calculate odds ratios of baseline patient and county factors associated with clozapine initiation. RESULTS: Among 629,809 unique antipsychotic treatment episodes, 79,934 showed service use patterns consistent with treatment resistance. Clozapine accounted for 2.5% of starts of antipsychotic medication among patients in the overall sample and for 5.5% of starts among patients with treatment resistance. Clozapine initiation was significantly associated with male sex, younger age, white race, more frequent outpatient service use for schizophrenia, and greater prior-year hospital use for mental health. Treatment resistance and living in a county with historically high rates of clozapine use were among the strongest predictors of clozapine use. CONCLUSIONS: The clozapine initiation rate was low compared with the expected proportion of patients who warrant a clozapine trial and was strongly affected by local treatment practices. Efforts to address irregular access to clozapine are needed to improve recovery opportunities for people with schizophrenia in the United States. PMID- 24233348 TI - Gambling: Philosophy and policy. PMID- 24233349 TI - Gambling and the Law((r)): Endless fields of dreams. AB - This article examines the current trends of proliferation of commercial gaming, especially in the United States, in the context of the "third wave" of legalization of gambling that has been experienced since the founding of the nation. The author looks at the historic foundations of the spread of casino style gambling, and notes the types of casino gaming that have led the way in the current expansion. He also points out why it is reasonable to expect that this wave too may come crashing down, as general acceptance of wide-spread casino gaming in America may indeed be short-lived. PMID- 24233345 TI - Minimally invasive follicular thyroid cancer (MIFTC)--a consensus report of the European Society of Endocrine Surgeons (ESES). AB - BACKGROUND: This paper aims to review controversies in the management of minimally invasive follicular thyroid carcinoma (MIFTC) and to reach an evidence based consensus. METHOD: MEDLINE search of the literature was conducted using keywords related to MIFTC. The search term was identified in the title, abstract, or medical subject heading. Available literature meeting the inclusion criteria were assigned the appropriate levels of evidence and recommendations in accordance with accepted international standards. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to MIFTC. RESULTS: Published papers on MIFTC present inadequate power with a III-IV level of evidence and C grade of recommendation. Several issues demanded a comparison of published studies from different medical reports regarding MIFTC definition, specimen processing, characteristics, diagnosis, prognoses, and therapy. As a consequence, it is difficult to make valuable statements on MIFTC with a sufficient recommendation rating. MIFTC diagnosis requires clearer, unequivocal, and reproducible criteria for pathologist, surgeons, and endocrinologists to use in the management of these patients. If the distinction between MIFTC and WIFTC cannot be made, an expert in thyroid pathologist should be consulted. CONCLUSION: According to published papers, the following conclusions can be drawn. (a) Candidates for hemithyroidectomy are MIFTC with exclusive capsular invasion, patients <45 years old at presentation, tumor size <40 mm, without vascular invasion, and without any node or distant metastases. (b) Candidates for total thyroidectomy are MIFTC in patients >=45 years at presentation, tumor size >=40 mm, vascular invasion present, positive nodes, and positive distant metastases. (c) In the absence of clinical evidence for lymph node metastasis, patients with MIFTC do not require prophylactic lymph node dissection. (d) Radio iodine ablation is indicated in elderly patients (>45 years), large tumor size (>40 mm), extensive vascular invasion, presence of distant synchronous or metachronous metastasis, positive nodes, and if recurrence is noted at follow-up. PMID- 24233350 TI - The roots, significance, value and legislation of gambling. AB - In this highly personal account, Reverend Moody traces his exploration for over three decades of many facets of the underlying nature of gambling in society and in human nature. He makes the case that much of the appeal of gambling comes from the excitement of "playing with chance," and discusses how different types of gambling - lotteries, wagering, and continuous betting - meet a variety of needs and pose diverse levels of risk to gamblers. He notes distinctions between "controlled" and "uncontrolled" gamblers, and the tendency for controlled gamblers to play on the edge and risk loss of control. He notes difficulties in preventing the excesses that can occur to individuals who gamble. He points out the problems with legislatures legalizing gambling for ulterior purposes, such as to raise tax revenue, rather than to cater to the demand for gambling from punters. This can lead to situations where commercial gaming interests are not directed to act in the best interests of the general public because potential problems that may arise with available gambling are ignored or deemphasized. Finally, he points out the tensions amongst various interest groups who deal with gambling and notes those forums which have evolved in recent years that provide greater opportunities for dialogue among the various entities who deal with gambling and public policy issues. PMID- 24233351 TI - The philosophical foundations of Las Vegas. AB - Las Vegas is a city that has long challenged social norms of the rest of the United States and built a highly successful economic base on gambling and other hedonistic pursuits. Now that many other states and communities are pursuing or actively considering following the route of legal casinos for economic development purposes, the ethical considerations that have confronted Las Vegas about the question of gambling and its broader social impacts take on greater import.This paper examines the ethics of gambling relative to Las Vegas at two levels: first, as a pragmatic trade-off of accepting an activity with some bad consequences because of the economic benefits that can be derived; and second, more fundamentally, by examining the validity of the major ethical arguments against gambling. PMID- 24233352 TI - Art & craft: Creative fiction and Las Vegas. AB - This article provides a review of the contrasting ways in which modern essayists and novelists have reflected their experience of Las Vegas. The author suggests that while Las Vegas may serve as a convenient symbol for depression and alienation, contemporary fiction also celebrates Las Vegas for its life-enhancing impact. These themes are fused with surreal imagination in the novelKeno Runner by David Kranes. PMID- 24233353 TI - Play grounds. AB - The author discusses the ambience presented by casinos to their customers. He explores the issues of space as an attraction to people being brought into casinos for the purpose of "play" and the compatibility of the casino's internal design with the concept of "welcoming" space and its degree of legibility: how well a first time visitor can "read" the activities and opportunities within its spaces. PMID- 24233354 TI - Stable Suppression of Lactate Dehydrogenase Activity during Anoxia in the Foot Muscle of Littorina littorea and the Potential Role of Acetylation as a Novel Posttranslational Regulatory Mechanism. AB - The intertidal marine snail, Littorina littorea, has evolved to withstand extended bouts of oxygen deprivation brought about by changing tides or other potentially harmful environmental conditions. Survival is dependent on a strong suppression of its metabolic rate and a drastic reorganization of its cellular biochemistry in order to maintain energy balance under fixed fuel reserves. Lactate dehydrogenase (LDH) is a crucial enzyme of anaerobic metabolism as it is typically responsible for the regeneration of NAD(+), which allows for the continued functioning of glycolysis in the absence of oxygen. This study compared the kinetic and structural characteristics of the D-lactate specific LDH (E.C. 1.1.1.28) from foot muscle of aerobic control versus 24 h anoxia-exposed L. littorea. Anoxic LDH displayed a near 50% decrease in V max (pyruvate-reducing direction) as compared to control LDH. These kinetic differences suggest that there may be a stable modification and regulation of LDH during anoxia, and indeed, subsequent dot-blot analyses identified anoxic LDH as being significantly less acetylated than the corresponding control enzyme. Therefore, acetylation may be the regulatory mechanism that is responsible for the suppression of LDH activity during anoxia, which could allow for the production of alternative glycolytic end products that in turn would increase the ATP yield under fixed fuel reserves. PMID- 24233355 TI - Intraoperative flash VEPs are reproducible in the presence of low amplitude EEG. AB - Flash visual evoked potentials (FVEPs) are often irreproducible during surgery. We assessed the relationship between intraoperative FVEP reproducibility and EEG amplitude. Left then right eyes were stimulated by goggle light emitting diodes, and FVEPs were recorded from Oz-Fz' (International 10-20 system) in 12 patients. Low cut filters were <=5 Hz in all patients; two patients also had recordings using 10 and 30 Hz. The reproducibility of FVEP and the amplitude of the concomitant EEG from C4'-Fz were measured. Nine patients had low amplitude EEG (<30 MUV); reproducible FVEPs were obtained from all eyes with normal pre operative vision. The other three patients had high amplitude EEG (>50 MUV); FVEPs were absent from three of four eyes with normal pre-operative vision (the other normal eye had a present but irreproducible FVEP). Raising the low cut filter to 10 and 30 Hz (in two patients) progressively reduced EEG and FVEP amplitude, reduced amplifier blocking time and improved FVEP reproducibility. FVEPs were more reproducible in the presence of low amplitude EEG than high amplitude EEG. This is the first report describing the effect of EEG amplitude on FVEP reproducibility during surgery PMID- 24233356 TI - Morphogenic and genetic stability in longterm embryogenic cultures and somatic embryos of Norway spruce (Picea abies {L.} Karst). AB - Embryogenic cultures were initiated from mature zygotic embryos of Picea abies. The somatic embryos in the embryogenic cultures were first stimulated to mature and then either to develop further into plantlets or to differentiate new embryogenic cultures. The procedure was repeated three times during two years. The ability to give rise to new embryogenic cultures or to develop into plantlets was similar for all somatic embryos irrespective of how long they had been cultured in vitro. The nuclear DNA content, measured in a flow cytometer, was estimated at 32 pg/G1 nuclei in seedings developed from zygotic embryos. Nuclei isolated from embryogenic cultures and from plantlets regenerated from somatic embryos had the same DNA content as those isolated from seedlings. PMID- 24233357 TI - Plant regeneration from pea protoplasts via somatic embyogenesis. AB - Plant regeneration via somatic embryogenesis was obtained from pea protoplasts. Strong auxins (picloram or 2.4-D) and increased osmolarity of the medium were necessary for embryo induction. Relatively high amounts of embryogenic calli could be obtained in 2 genotypes. After a period on hormone-free medium, a second induction of somatic embryos was possible. Further development of somatic embryos was accomplished on GA3 - containing medium. PMID- 24233358 TI - Plant regeneration and protoplast culture of Browollia speciosa. AB - Explants from hypcotyls and cotyledons of Browalia speciosa were shown to regenerate plantlets.Protoplasts were isolated from etiolated cotyledon material, and, although callus was readily obtained, plantlet regeneration was not observed using numerous hormone regimes. PMID- 24233359 TI - Successful cocultivation of Brassica napus microspores and proembryos with Agrobacterium. AB - Brassica napus microspores and microspore-derived proembryos were cocultivated with Agrobacterium tumefaciens harbouring a binary vector. The vector contained selectable genes for kanamycin and hygromycin antibiotic resistance. Microspores and proembryos survived the cocultivation procedure and subsequent antibiotic selection. Thousands of plantlets can be regenerated from a single experiment. Biochemical analysis indicated up to 7.3% of plants exhibited neomycin phosphotransferase II enzyme activity. Success of the cocultivation procedure depended largely on choosing the proper coculture conditions while allowing microspore embryogenesis to proceed. PMID- 24233360 TI - Production of flavanone-neohesperidosides in Citrus embryos. AB - Grapefruit (Citrus paradisi) tissue cultures were examined for qualitative and quantitative changes in flavanone-neohesperidoside content during somatic embryogenesis. Embryos cultured in vitro contain naringin and a rhamnosyl transferase activity which is capable of rhamnosylating position 2 on the flavanone glucosides. Rhamnosylation is carried out only in embryos cultivated on solid medium but not in embryos grown in suspension cell cultures. PMID- 24233361 TI - Plant regeneration from hypocotyl and petiole callus of Trifolium pratense L. AB - Red clover (Trifolium pratense L.) seedlings were screened for the ability to regenerate plantlets from hypocotyl-derived callus tissue. Media sequences described by Beach and Smith (1979) and Collins and Phillips (1982) and a variation using media from both sequences were tested. Plantlets were regenerated from three out of 642 genotypes. In all three cases, callus was initiated on B5C medium and regeneration was accomplished on SPL medium. Attempts to regenerate plants from petiole-derived callus tissue have so far been successful only with regenerants of clone F49. Petiole callus from epicotyl-derived F49 plants proved to be non-regenerative. Pollen viability varied significantly among individuals regenerated from callus cultures of clone F49. Root tip squashes from F49 regenerants revealed the normal diploid chromosome number (2n=14). The frequency of regeneration within progeny from reciprocal crosses between F49 regenerants and several non-regenerative genotypes was 29%. PMID- 24233362 TI - A microtest system for the serial assay of phytotoxic compounds using photoautotrophic cell suspension cultures of Chenopodium rubrum. AB - Chenopodium rubrum photoautotrophic cell suspensions were grown in plastic tissue culture dishes under photoautotrophic conditions. Growth was monitored by measuring cell number, packed cell volume, chlorophyll content and oxygen production. Such microtiter dishes are suitable systems for the serial assay of growth inhibition and various physiological effects (i.e. chlorophyll fluorescence, cell viability, oxygen production) of photoautotrophic cells as caused by herbicides and fungal phytotoxins. The applicability of the test system is discussed. PMID- 24233363 TI - Shoot regeneration from petioles and leaves of Vitis X labruscana 'Catawba'. AB - Shoot regeneration and normal plants were obtained from leaf and petiole explants derived from in vitro grown shoots of Vitis X labruscana 'Catawba'. Regeneration was induced in the presence of both 6-benzylaminopurine and indole-3-butyric acid; combinations of 2,4-dichlorophenoxyacetic acid or 2-naphthoxyacetic acid with 6-benzylaminopurine did not permit regeneration from leaf explants. Up to 15% of leaf and 70% of petiole explants regenerated shoots on media with 5.0-10.0 MUM BA and 0.1-0.5 MUM IBA. Incubation in the dark was required to obtain regeneration. About 50% of shoots developed normally following transfer to light. An average of one shoot regenerated from leaf explants and 3.3 shoots regenerated per petiole explant. Regeneration from petioles and leaves was always from the basipetal end. The interaction of 6-benzylaminopurine with indole-3-butyric acid was also examined. PMID- 24233364 TI - Differential characteristics of cell suspension cultures initiated from Eucalyptus gunnii clones differing by their frost tolerance. AB - Cell suspension cultures were initiated from two clones of Eucalyptus gunnii differing by their frost resistance.During cold treatments viability of the individual cell lines and of their protoplasts was correlated to the degree of frost resistance of the starting clones.Moreover, at moderate temperature (10 degrees C) the growth rate was higher for the tolerant cells than for the sensitive ones.Free proline content was ten-fold higher in the resistant cell line than in the sensitive one whereas concentrations of other free amino-acids were equivalent. PMID- 24233365 TI - Development of salt tolerant lines of KDML and LPT rice cultivars through tissue culture. AB - Salt tolerant lines of indica rice (Oryza sativa L.) were selected out of KDML and LPT cultivars. The first selection was made in vitro by incorporating 1 or 2% NaCl in the culture media. Embryogenic calli from mature embryo were subjected to a salt stress for four weeks. Regeneration rates after salt stress were reduced to 0.076% or less as against regeneration rates of 8.3 to 30% normally obtained for non-stressed conditions. Seedlings of regenerants and of following generations were treated with 0.5% NaCl in water culture for four weeks. Definite salt tolerance of the progenies of selected and unselected plants appeared in both cultivars. The best survival rate of line LPT 171 in R3 was 94.3% while only 2% of the control survived. The result of the fourth generation was similar to the third. PMID- 24233366 TI - Ethylene production and embyogenesis from anther cultures of barley (Hordeum vulgare). AB - Ethylene production was measured in cultured barley (Hordeum vulgare L.) anthers. The pattern of ethylene production and the content of the ethylene precursor 1 aminocyclopropane-1-carboxylic acid (ACC) were different among cultivars. Ethylene production appeared to be related to embryogenesis (callus and embryo production). In cultivars in which anthers had low amounts of ACC and produced ethylene slowly, the addition of ethylene promotors (Ethrel or ACC) increased embryogenesis. However, in the cultivar Klages, in which anthers had high amounts of ACC and produced ethylene rapidly, the addition of an ethylene production inhibitor (putrescine) increased embryogenesis. Thus, an optimum level of ethylene production appears to be important for embryogenesis. The differences in anther response and callus production among cultivars may be due to both the capacity to produce ethylene and the sensitivity to high ethylene levels. PMID- 24233367 TI - Survival of cultured cells and somatic embryos of Asparagus officinalis cryopreserved by vitrification. AB - Cultured cells and somatic embryos derived from the mesophyll tissue of asparagus (Asparagus officinalis L.) were cryopreserved by vitrification. The vitrification solution (PVS) contains (w/v) 22% glycerol, 15% ethylene glycol, 15% propylene glycol and 7% DMSO in Murashige-Skoog medium enriched with 0.5M sorbitol. After initial cryoprotection with sorbitol supplemented MS medium containing 12% ethylene glycol, cells or embryos were exposed stepwise to 85% PVS at 0 degrees C. They were loaded into 0.5 ml transparent straws, and were then plunged directly into liquid nitrogen. After rapid warming, PVS was removed and diluted stepwise. The highest survivals of vitrified cells and embryos were about 65 and 50%, respectively. Surviving embryos developed into plantlets. PMID- 24233368 TI - Effect of exogenous amino acids on the intracellular content of proline and other amino acids in Daucus carota cells. AB - The effect of tryptophan on the biosynthesis of proline has been investigated. Cells of Daucus carota grown in B5 medium supplemented with 5*10(-4)M tryptophan acquired the ability to grow in the presence of inhibitory concentrations of azetidine-2-carboxylic acid, an analog of proline. When trp was added to carrot cell cultures at sub-growth inhibiting concentrations, overproduction of intracellular free proline was observed. An increase was also observed for lys, his, ala, leu and phe. Likewise, the addition of asparagine, glutamic acid and phenylalanine to the medium stimulated the intracellular increase of free proline and other amino acids. PMID- 24233369 TI - Antiplasmodial activity of Artemisia annua plant cell cultures. AB - Extracts of Artemisia annua cultures have been assessed for in vitro activity against the malarial parasite Plasmodium falciparum. Callus and suspension cells and medium were analysed and examined for their activity at different stages of growth and development. Time-course experiments were carried out to investigate the influence of various basal media, plant growth regulators and light on both growth and possible artemisinin production. Two active fractions were obtained but artemisinin was not detected. PMID- 24233370 TI - Editorial: Ecological monitoring for global change. PMID- 24233371 TI - Ecosystem monitoring at global baseline sites. AB - Integrated ecosystem and pollutant monitoring is being conducted at prototype global baseline sites in remote areas of the Noatak National Preserve, Alaska, the Wind River Mountains, Wyoming, and Torres del Paine National Park, Chile. A systems approach has been used in the design of these projects. This approach includes: (1) evaluation of source-receptor relationships, (2) multimedia (i.e., air, water, soil, biota) monitoring of key contaminant pathways within the environment, (3) the use of selected ecosystem parameters to detect anthropogenic influence, and (4) the application of a systems conceptual framework as a heuristic tool.Initial short-term studies of air quality (e.g. SO2, NO2) plus trace metal concentrations in mosses generally indicate pristine conditions at all three of the above sites as expected although trace metals in mosses were higher at the Wyoming site. Selected ecosystem parameters for both terrestrial (e.g. litter decomposition) and aquatic (e.g. shredders, a macroinvertebrate functional feeding group) habitats at the Wyoming site reflected baseline conditions when compared to other studies.Plans also are being made to use U.S. Department of Energy Research Parks for global change monitoring. This will involve cross-site analyses of existing ecological databases and the design of a future monitoring network based on a systems approach as outlined in this paper. PMID- 24233372 TI - Results from the NOAA National Status and Trends Program on distribution and effects of chemical contamination in the coastal and estuarine United States. AB - The NOAA National Status and Trends (NS&T) Program has been monitoring chemical contamination in fish livers, and surface sediments since 1984 and in molluscan tissue and sediments since 1986. Data from fine-grained sediment at 175 sites are used to describe the spatial distribution of contamination throughout the coastal and estuarine United States. Highest levels are generally found in, and considered representative of, urban areas. It should be noted, however, that these levels are not as high as have been found near discharge pipes or in isolated industrial areas through other monitoring efforts. Dramatic biological responses, such as liver tumors in fish or apparently toxic contaminant levels in sediment, are found infrequently. Subtle biological changes, especially those that affect reproductive ability, are being sought. Data from three annual collections of mollusks have been used to identify early signals of temporal trends in contamination at NS&T sites. PMID- 24233373 TI - Long-term monitoring for environmental change in U.S. National Parks a watershed approach. AB - The U.S. National Park Service (NPS) is faced with direct questions about the condition of Park natural resources. The watershed approach to long-term monitoring of natural, and remote areas within the National Parks has provided important data for detecting both spacial and temporal changes in environmental conditions. These data collections allow the partitioning of cause and effect relationships of ecological change within a given watershed. They also serve to meet both reference and early warning objectives. Success in advancing a number of 'acid precipitation' goals has demonstrated the usefulness of these integrated watershed data for inter-ecosystem comparison and for analogy between watersheds. The watershed program owing to the NPS experience is proposed as a model for focusing the National Park Service's inventory and monitoring program inititiative. This approach provides to park researchers and resources managers the needed tools for dealing with today's complex local, regional and global natural resources issues. PMID- 24233374 TI - An EPA program for monitoring ecological status and trends. AB - Despite hundreds of millions of dollars spent annually in the United States on environmental monitoring, policy and decision makers seldom have ready access to monitoring data to aid in prioritizing reasearch and assessment efforts or to assess the extent to which current policies are meeting the desired objectives. EPA is currently conducting research to evaluate options for establishing an integrated, cooperative monitoring program, with participation by federal, state, and private entities, that could result in annual statistical reports and interpretive summaries on the status and trends in indicators of adverse disturbance and corresponding 'health' of the nation's ecosystem on the regional and national scale. PMID- 24233375 TI - Near-field time-resolved fluorescence studies of poly(phenylmethyl silane) with subwavelength resolution. AB - We present an example of the first time-correlated single-photon counting (TCSPC) near-field optical measurement. The aperture size of our prepared aluminun-coated fiber-optic probe was approximately 50 nm, which represents a spatial resolution of lambdaex/7 for our UV measurements. Near-field fluorescence decays of poly(phenylmethyl silane) in solid thin films excited in the range 325-360 nm were obtained and the steady-state excitation spectra compared with the excitation spectral information obtained in the far field. Fluorescence decays showed single exponential lifetimes ranging from 45 to 277 ps, which was dependent on the excitation wavelength and the selected near-field tip. The proximity of the metal-coated tip to the sample may be the reason for the modulation in fluorescence lifetime. PMID- 24233376 TI - Photobleaching with a subnanosecond laser flash. AB - In standard fluorescence recovery after photobleaching (FRAP) applications for measuring lateral diffusion rates and adsorption/desorption kinetics of fluorescent molecules at biological or model membranes, irreversible bleaching is induced by a bright excitation flash of at least millisecond time scale. It has been presumed that the bleaching event is of a low probability and the significant bleached population that develops during the flash results from each molecule undergoing thousands of excitation/deexcitation cycles before a bleaching event occurs. In some FRAP experiments, notably polarized FRAP (PFRAP) for measuring molecular rotational diffusion rates, it is desirable to use much shorter (subnanosecond) bleaching pulses. However, subnanosecond pulses are shorter than the fluorescence lifetime, so that any fluorophore will experience at most only one visit to the excited state during the bleaching pulse. If bleaching occurs only by the same processes as in slower FRAP experiments, one would thereby expect only minimal bleaching regardless of the bleach intensity. Moreover, the ability of fast polarized pulses to imprint an anisotropic orientational pattern in the postbleach unbleached fluorophore, an ability essential for PFRAP, is not at all guaranteed, particularly if two-photon processes are involved in high-intensity short bleach pulses. In this study, bleaching depths are measured as a function of subnanosecond pulse intensity on a small labeled protein covalently immobilized on fused silica. We show that bright subnanosecond laser flashes do indeed produce significant bleaching, that both two photon effects and reversible bleaching are involved, and that polarized bleaching does produce an anisotropic orientational pattern of unbleached fluorophore. We also postulate a theoretical molecular state model which semiquantitatively accounts for the experimentally observed dependence of reversible bleaching on bleaching pulse intensity. PMID- 24233377 TI - A method for quantitative interpretation of fluorescence detection of poly(ethylene glycol)-mediated 1-palmitoyl-2-[[[2-[4-(phenyl-trans-1,3,5 hexatrienyl) phenyl]ethyl]oxyl]carbonyl]3-sn-phosphatidylcholine (DPHpPC) transfer and fusion between phospholipid vesicles in the dehydrated state. AB - A method has been developed for calculating the expected fluorescence lifetime of the DPH p PC probe distributed between different membrane environments. We show how this method can be used to distinguish between lipid transfer and fusion between large unilamellar vesicles occurring in the presence of poly(ethylene glycol) (PEG). This application of the calculation took into consideration the heterogeneity of microenvironments experienced by the probe in a sample containing vesicle aggregates of different sizes. Assuming that the aggregate size distribution was a delta function of the aggregate size, comparison of the calculated and observed lifetimes yielded an estimate of the vesicle aggregate size. For vesicles of varying compositions in the presence of dehydrating concentrations of PEG, this method suggested that only small aggreggates formed. For vesicles that could be demonstrated by other means not to have fused, the data were consistent with lipid transfer occurring only between the outer leaflets of two to four vesicles, even at high PEG concentrations. For vesicles that could be demonstrated to fuse by contents mixing and size changes, the fluorescence lifetime data were consistent with lipid transfer between both the inner and the outer leaflets of two to four fused vesicles. At very high PEG concentrations, where extensive rupture and large, multilamellar products were previously observed, the lifetime data were consistent with much more extensive lipid transfer within larger aggregates. The agreement of predictions made on the basis of lifetime measurements with other observations attests to the validity of the fluorescence lifetime method. In addition, the model and data presented here provide evidence that fusion occurs between small numbers of PEG-aggregated vesicles before the removal of PEG. PMID- 24233378 TI - Evidence for dual La and L b emission in 5-methylindole. AB - The steady-state fluorescence anisotropy of 5-methylindole is shown to depend on both excitation and emission wavelengths, at room temperature in glycerol. A simulation is presented that shows that this emission wavelength dependence of the anisotropy can be explained in terms of dual emission from both the La and the Lb transition moments of the indole ring. For such dual emission to occur, the lowest excited-state energy level of both of these oscillators must be very similar. PMID- 24233379 TI - Distributions of fluorescence decay times for synthetic melittin in water methanol mixtures and complexed with calmodulin, troponin C, and phospholipids. AB - Frequency-domain measurements of the intensity decays of melittin were used to recover the distribution of decay times displayed by its single tryptophan residue. Melittin was examined in the monomeric random coil state (water), in the monomeric alpha-helical state (water-methanol), in the tetrameric state, and with 6M guanidine hydrochloride. In the presence of denaturant, where melittin is expected to be devoid of secondary structure, we observed a narrow distribution of lifetimes, similar to a double-exponential decay. In water the intensity decay of melittin was found to be described better by the distribution of decay times, which became progressively wider as the amount of alpha-helix was increased by the methanol cosolvent or upon formation of the alpha-helical tetrameric state. We also examined the intensity decays of melittin when complexed with calmodulin, troponin C, or lipid vesicles of 1-palmitoyl-2-oleyl-L-alpha-phosphatidylcholine (POPC). The lifetime distributions of the complexes with lipid were comparable to those observed in methanol-water, suggesting a similarity of the structure and/or dynamics of the environment surrounding the tryptophan residue. A broad lifetime distribution was observed for the melittin-calmodulin complex, suggesting a rigid structure and/or heterogeneity in the form of the complex. The lifetime distribution of the melittin-troponin C complex was more narrow, suggesting a more uniform structure, at least in the region surrounding the tryptophan residue. These results demonstrate that the lifetime distributions of a single tryptophan protein can be a sensitive indicator of the conformational heterogeneity and dynamics of proteins. PMID- 24233380 TI - Spectroscopic properties of the photoproducts of pyridoxal-5'-P irradiation: Catalytic site recognition of ribonuclease A. AB - Photoproducts of pyridoxal-5'-P, i.e., 4-pyridoxic-5'-P and bis-pyridoxal-5'-P, have been studied by spectroscopic methods. The spectroscopic properties of bis pyridoxal-5'-P (bis-PLP) resemble those of pyridoxal-5'-P (PLP) under similar experimental conditions. The coupling of methylen hydrogens to the phosphorus atom has been shown by NMR spectroscopy. The singlet in the(31)P-NMR spectra and the triplet in(1)H-undecoupled experiments confirm the presence of the phosphate group in the 5' position of the structure of the vitamin. The effect of pH and solvent composition on the relative distribution of species of bis-pyridoxine-5' P (bis-PNP) has been investigated by absorption and fluorescence spectroscopy. The acid-base dissociation of the phosphate group is easily detected by emission spectroscopy. Bis-PNP and bis-PLP bind to the enzyme RNase A and they behave as competitive inhibitors with respect to the substrate cytidine-2'-3'-cyclic phosphate. The natural forms of vitamin B6, pyridoxine, and pyridoxine-5'-P have no effect on the catalytic activity of the protein. Experimental evidence derived from fluorescence and inhibition experiments is consistent with the hypothesis that bis-PNP recognizes the catalytic site of RNase A. PMID- 24233381 TI - Oxygen fluorescence quenching studies with single tryptophan-containing proteins. AB - The work of Lakowicz and Weber [Biochemistry 12, 4161 (1973)] demonstrated that molecular oxygen is a powerful quencher of tryptophan fluorescence in proteins. Here we report studies of the oxygen quenching of several proteins that have a single, internal tryptophan residue. Among these are apoazurin (Pseudomonas aeruginosa), asparaginase (Escherichia coli), ribonuclease T1 (Aspergillus oryzae), and cod parvalbumin. Both fluorescence intensity and phase lifetime quenching data are reported. By comparison of these data we find that there is a significant degree of apparent static quenching in these proteins. The dynamic quenching rate constants,k q, that we find are low compared to those for tryptophan residues in other proteins. For example, for apoazurin we find an apparentk q of 0.59*10(9) M (-1) s(-1) at 25 degrees C. This value is the lowest that has been reported for the oxygen quenching of tryptophan fluorescence. PMID- 24233382 TI - Steady-state and time-resolved phosphorescence of wild-type and modified bacteriophage lambdacI repressors. AB - We have measured the steady-state phosphorescence and decay times of wild-type lambdacI repressor and compared it with that of a modified lambdacI repressor in which > 95% of the tryptophans were replaced with 5-hydroxy-L-tryptophan (5 OHTrp). The wild-type and 5-OHTrp-lambdacI repressors are spectroscopically distinct such that we can selectively excite the 5-OHTrp-lambdacI even in the presence of a 15-fold molar excess ofN-acetyltryptophanamide (NATrpA). The phosphorescence band of wild-type lambdacI is red-shifted by 3 nm relative to NATrpA, characteristic of buried tryptophan. Similarly, the phosphorescence of 5 OHTrp-lambdacI repressor is red-shifted relative to the model, 5-OHTrp, showing that according to the phosphorescence, the modified repressor is structurally indistinguishable from the native repressor. While the phosphorescence decay of both NATrpA and 5-OHTrp are single exponentials, the decay of both wild-type and 5-OHTrp-lambdacI repressors is complex, requiring three decay components whose fractional contributions to the phosphorescence are the same for both repressors. Because the 5-OHTrp phosphorescence can be excited at wavelengths outside the absorbance range of tryptophan and DNA, a protein spectrally enhanced with this emitter will aid the investigations of protein-protein or protein-DNA interactions. PMID- 24233383 TI - Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collagen-induced arthritic rats: a population approach. AB - The PK/PD of abatacept, a selective T cell co-stimulation modulator, was examined in rats with collagen-induced arthritis (CIA) using a nonlinear mixed effect modeling approach. Male Lewis rats underwent collagen induction to produce rheumatoid arthritis. Two single-dose groups received either 10 mg/kg intravenous (IV) or 20 mg/kg subcutaneous (SC) abatacept, and one multiple-dose group received one 20 mg/kg SC abatacept dose and four additional 10 mg/kg SC doses. Effects on disease progression (DIS) were measured by paw swelling. Plasma concentrations of abatacept were assayed by enzyme-linked immunosorbent assay. The PK/PD data were sequentially fitted using NONMEM VI. Goodness-of-fit was assessed by objective functions and visual inspection of diagnostic plots. The PK of abatacept followed a two-compartment model with linear elimination. For SC doses, short-term zero-order absorption was assumed with F = 59.2 %. The disease progression component was an indirect response model with a time-dependent change in paw edema production rate constant (k in ) that was inhibited by abatacept. Variation in the PK data could be explained by inter-individual variability in clearance and central compartment volume (V 1 ), while the large variability of the PD data may be the result of paw edema production (k in 0 ) and loss rate constant (k out ). Abatacept has modest effects on paw swelling in CIA rats. The PK/PD profiles were well described by the proposed model and allowed evaluation of inter-individual variability on drug- and DIS-related parameters. PMID- 24233384 TI - Effect of Korean Red Ginseng on radiation-induced bone loss in C3H/HeN mice. AB - This study investigated the effects of Korean Red Ginseng (KRG) on radiation induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray) groups. The irradiated mice were treated for 12 wk with vehicle, KRG (per os, p.o.) or KRG (intraperitoneal). Serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase, estradiol level, and biomechanical properties were measured. Tibiae were analyzed using micro-computed tomography. Treatment of KRG (p.o., 250 mg/kg of body weight/d) significantly preserved trabecular bone volume, trabecular number, structure model index, and bone mineral density of proximal tibia metaphysic, but did not alter the uterus weight of the mice. Serum ALP level was slightly reduced by KRG treatment. However, grip strength, mechanical property, and cortical bone architecture did not differ among the experimental groups. The results indicate that KRG can prevent radiation-induced bone loss in mice. PMID- 24233385 TI - Superaromatic terpyridines based on corannulene responsive to metal ions. AB - Two superaromatic terpyridine ligands (1 and 2) incorporating a corannulene unit at the 4'-position are reported. The optical and metal sensing properties of both ligands were investigated by the naked eye, and UV-vis and fluorescence spectroscopy in this work. In 1, the corannulene motif is directly connected to the 4'-phenylterpyridine domain, while in 2, the corannulene motif and the 4' phenylterpyridine domain are separated by an acetylene linker. Both 1 and 2 can work as chemosensors for metal ions and display different optical responses to various metal ions. It is shown that both ligands exhibit a colorimetric sensing ability for Fe(2+) through an obvious color change from colorless to magenta, and this color change can be observed easily by the naked eye. The addition of Fe(2+) also leads to significant changes in the absorption spectra of the ligands. A characteristic red shift in the emission spectra is observed in the presence of Zn(2+), which facilitates the discrimination of Zn(2+) from other metal ions. In addition, density functional theory (DFT) and time-dependent-density functional theory (TD-DFT) calculations were performed and shown to be consistent with the observed experimental results. PMID- 24233386 TI - Dysfunction of protein C anticoagulant system, main genetic risk factor for venous thromboembolism in northeast Asians. AB - Venous thromboembolism (VTE) is a life threatening medical disorder worldwide. A great deal of evidence suggests that prevalence of VTE varies significantly among ethnic populations, with consistently lower incidence found in Asians. While the distribution of genetic risk factors may vary among races, genetic risk factors can play a major role among individuals with different genetic backgrounds. Two clinically evaluated low-frequency genetic mutations that predispose to VTE--the factor V Leiden mutation and prothrombin G20210A mutation--are found predominantly in Caucasians, and virtually never in Asians. The findings of a recent genetic study of VTE in northeast Asians, which greatly advanced our knowledge in this area, indicate that the most frequent genetic risk factors for VTE in northeast Asians can be attributed to a dysfunction of the protein C anticoagulant system. Several low-frequency genetic mutations, PROS1 p.Lys196Glu in Japanese and PROC p.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity. Construction of a multifactorial model based on the genetic risk factors in the protein C anticoagulant system could facilitate genetic counseling for VTE risk in these populations. The influence of prevalent genetic mutations on the risk of VTE should be further investigated in Asian countries. PMID- 24233387 TI - Primary venous thromboembolism prophylaxis in patients with solid tumors: a meta analysis. AB - Venous thromboembolism (VTE) is a leading cause of death among outpatient chemotherapy patients. However the VTE preventive measures for outpatients are not widely advocated. We did a meta-analysis to evaluate the outpatient VTE prevention's effectiveness and safety. We searched electronic databases until the end of December 2012 and reviewed the abstracts and manuscripts following the PRISMA guidelines. Occurrence of first VTE event was the efficacy outcome. The safety end point was major bleeding. We calculated Q statistic and a homogeneity formal test. The odds ratio (OR) estimates were pooled by using the Mantel Haenszel fixed-effects method in the absence of heterogeneity. Data were analyzed using the R META package). We identified 1,485 articles and reviewed 37 articles based on initial screening. The number of patients included in 11 selected trials was 7,805. The odds of VTE was lower in the prophylaxis group (OR 0.56; 95% CI 0.45-0.71) and improved when heparin-based prevention was analyzed (OR 0.53; 95% CI 0.41-0.70). We found strong prevention among patients with lung cancer (OR 0.46; 95% CI 0.29-0.74) and pancreatic cancer (OR 0.33; 95% CI 0.16-0.67). Major bleeding events were frequent in the intervention group (OR 1.65; 95% CI 1.12 2.44). Thromboprophylaxis reduced VTE episodes. The VTE events were reduced by 47% in heparin-based prophylaxis trials compared to placebo. The patients receiving heparin-based prophylaxis had a 60% increase in bleeding events. Improving risk stratification tools to personalize prevention strategies may enhance the VTE prevention applicability in cancer patients. PMID- 24233388 TI - Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak, Malaysia. AB - Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6% (IQR 44.6-74.1%). Of the out-of-range readings, 30.0% were below range and 15.4% were above. INR variability, (standard deviation of individuals' mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95% CI 1.10-9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events. PMID- 24233389 TI - Hemostasis, cancer, and ABO blood group: the most recent evidence of association. AB - Human ABO blood group antigens are expressed on the surface of red blood cells and a variety of human cells and tissues. However, an increasingly number of studies show that the ABO blood group, in addition to its fundamental role in transfusion medicine and in several other disciplines, has a causal role in predisposing to several human diseases, including hemostasis and neoplastic disorders, which will be the focus of this narrative review. PMID- 24233390 TI - Temporal trends in the use of parenteral nutrition in critically ill patients. AB - BACKGROUND: Clinical practice guidelines recommend enteral over parenteral nutrition in critical illness and do not recommend early initiation. Few data are available on parenteral nutrition use or timing of initiation in the ICU or how this use may have changed over time. METHODS: We used the Project IMPACT database to evaluate temporal trends in parenteral nutrition use (total and partial parenteral nutrition and lipid supplementation) and timing of initiation in adult ICU admissions from 2001 to 2008. We used chi2 tests and analysis of variance to examine characteristics of patients receiving parenteral nutrition and multilevel multivariate logistic regression models to assess parenteral nutrition use over time, in all patients and in specific subgroups. RESULTS: Of 337,442 patients, 20,913 (6.2%) received parenteral nutrition. Adjusting for patient characteristics, the use of parenteral nutrition decreased modestly over time (adjusted probability, 7.2% in 2001-2002 vs 5.5% in 2007-2008, P<.001). Enteral nutrition use increased simultaneously (adjusted probability, 11.5% in 2001-2002 vs 15.3% in 2007-2008, P<.001). Use of parenteral nutrition declined most rapidly in emergent surgical patients, patients with moderate illness severity, patients in the surgical ICU, and patients admitted to an academic facility (P<=.01 for all interactions with year). When used, parenteral nutrition was initiated a median of 2 days (interquartile range, 1-3), after ICU admission and >90% of patients had parenteral nutrition initiated within 7 days; timing of initiation of parenteral nutrition did not change from 2001 to 2008. CONCLUSIONS: Use of parenteral nutrition in US ICUs declined from 2001 through 2008 in all patients and in all examined subgroups, with the majority of parenteral nutrition initiated within the first 7 days in ICU; enteral nutrition use coincidently increased over the same time period. PMID- 24233392 TI - Marine sponges as habitats of anaerobic phototrophic bacteria. AB - Enrichment cultures were prepared with different media for phototrophic bacteria from four species of marine sponges, collected from oxic coastal waters near Split (Yugoslavia). We obtained pure cultures of six strains ofChromatiaceae and two strains ofRhodospirillaceae by agar shake dilution. TheRhodospirillaceae were identified asRhodopseudomonas sulfidophila and a marine form ofRhodopseudomonas palustris. TheChromatiaceae were identified asChromatium vinosum, Chromatium gracile, Chromatium minutissimum. Ectothiorhodospira mobilis, and a Chromatium species, which in some respects resemblesChromatium minus. The occurrence of strictly anaerobic phototrophic bacteria in aerobic sponges is discussed with respect to nutrition and possible syntrophism. PMID- 24233391 TI - The prevalence of undiagnosed HIV serodiscordance among male couples presenting for HIV testing. AB - In the United States, a substantial proportion of HIV transmissions among men who have sex with men (MSM) arise from main sex partners. Couples voluntary HIV testing and counseling (CHTC) is used in many parts of the world with male-female couples, but CHTC has historically not been available in the U.S. and few data exist about the extent of HIV serodiscordance among U.S. male couples. We tested partners in 95 Atlanta male couples (190 men) for HIV. Eligible men were in a relationship for >=3 months and were not known to be HIV-positive. We calculated the prevalence of couples that were seroconcordant HIV-negative, seroconcordant HIV-positive, or HIV serodiscordant. We evaluated differences in the prevalence of HIV serodiscordance by several dyadic characteristics (e.g., duration of relationship, sexual agreements, and history of anal intercourse in the relationship). Overall, among 190 men tested for HIV, 11 % (n = 20) were newly identified as HIV-positive. Among the 95 couples, 81 % (n = 77) were concordant HIV-negative, 17 % (n = 16) were HIV serodiscordant, and 2 % (n = 2) were concordant HIV-positive. Serodiscordance was not significantly associated with any evaluated dyadic characteristic. The prevalence of undiagnosed HIV serodiscordance among male couples in Atlanta is high. Offering testing to male couples may attract men with a high HIV seropositivity rate to utilize testing services. Based on the global evidence base for CHTC with heterosexual couples and the current evidence of substantial undiagnosed HIV serodiscordance among U.S. MSM, we recommend scale-up of CHTC services for MSM, with ongoing evaluation of acceptability and couples' serostatus outcomes. PMID- 24233393 TI - The ecology of yeast flora associated with cactiphilic Drosophila and their host plants in the Sonoran desert. AB - Yeasts were isolated from the rotting stems of 7 species of cereoid cacti and 4 species ofDrosophila which utilize them as host plants. The yeast most common among 132 nonidentical isolates from the cacti and 187 nonidentical isolates from the flies, respectively, were:Pichia membranaefaciens (59 and 126),Candida ingens (22 and 8),Torulopsis sonorensis (16 and 20), andCryptococcus cereanus (11 and 14). Isolates capable of utilizingD-xylose were recovered primarily fromD. pachea andL. schotti. Adult flies were present on the substrates whenP. membranaefaciens was at high concentrations. As the pH of the substrates increased, the percent ofC. ingens cells increased relative to other yeast species. Larvae were detected mainly in alkaline substrates, and since adults did not yieldC. ingens to the extent the substrates did,C. ingens may be important in larval nutrition.Torulopsis sonorensis was recovered mainly fromD. mojavensis and its host plants,M. gummosus andL. thurberi. The concentration ofT. sonorensis in the substrates was negatively correlated with the temperature of the substrate.Cryptococcus cereanus was found in high concentrations in suitable tissues for adult flies but most adults did not yield this species to any extent. The yeast habitat diversities from the substrates had the following order:L. thurberi > C. gigantea > C. gigantea soils ? M. gummosus > L. schotti > others. Habitat diversity is discussed in relation to the variation of the physical conditions and chemical composition of the substrates. The yeast habitat diversities from the flies had the orderD. pachea > D. mojavensis ? D. nigrospiracula > undescribed Species M. The degree of habitat diversity is possibly a function of the surface feeding behavior of the flies. PMID- 24233394 TI - Occurrence ofVibrio and other bacteria on the sea nettle,Chrysaora quinquecirrha. AB - Sixty-two specimens of the sea nettle,Chrysaora quinquecirrha, were caught in the lower Chesapeake Bay, homogenized, and samples plated on a yeast extract-Bay water agar. Bacterial colonies were selected randomly, purified, and tested for 180 characteristics. Computer analysis permitted clustering of the 208 isolates into 15 groups (comprised of 133 strains) plus 75 nongrouped strains which failed to associate with any group at the 70% similarity level. The majority of the isolates (68.8%) wereVibrio species. These included 110 of the grouped strains (forming 12 of the 15 groups) and 33 of the nongrouped strains. The remainder of the isolates were distributed as follows:Pseudomonas (11.6%),Bacillus (8.2%),Flavobacterium (2.4%),Acinetobacter (2.4%),Moraxella (1.9%),Cytophaga (1.9%), Gram-positive cocci (1.4%), and miscellaneous (1.4%). All theBacillus were isolated from a group of moribund nettles and reflect an abnormal condition.Vibrio species predominated in the five "catches" of healthy nettles, but were distinctly different for each catch. PMID- 24233395 TI - Effects of temperature on the darkness survival of marine microplanktonic algae. AB - Thirty-seven species of marine microplanktonic algae from 10 taxonomic classes were tested for their viability in axenic culture after prolonged exposure to darkness at 2 degrees , 10 degrees , and 20 degrees C. The darkness test periods were prolonged in weekly installments up to a maximum of 1 year, and viability retention (survival) was judged from the capability for resuming growth after replacement in light. The 2 degrees C-tests showed 32% of the species reaching the limits of survival with 5-6 months of darkness exposure, but another similar percentage continued to tolerate darkness for double this period. These darkness toleration limits were considerably shorter at 20 degrees C for the strains known to be isolated from cold marine regions, whereas the warm-water strains showed the reverse temperature effect in surviving significantly longer at 10 degrees 20 degrees C than at 2 degrees C. Irrespective of temperature or algal class, the bulk of the more resistant survivors was formed by the strains qualifying as benthic types, about 70% of which tolerated 11-12 months and the rest at least 5 6 months of darkness. A few randomly chosen benthic strains extended this toleration to 3 years of darkness. It was concluded that phytoplankters retain darkness-endurance capacity determined by their ecological origin and with no obvious taxonomic correspondence. The concept of ecological races, characterized by temperature control of darkness survival, is discussed. PMID- 24233396 TI - The rate of microbial degradation of oil in a beach gravel column. AB - An automatic, continuous flow respirometer was used to follow the bio-oxidation of a crude oil in a column of fairly coarse beach material. A number of water percolation rates were employed, with and without inorganic nutrient supplementation (nitrate and phosphate). Initially, nutrient supplementation was required to allow significant oxidation rates, but a capacity for biodegradation in the absence of continued supplementation developed slowly. The increase in oxidation rate with nutrient supplementation was in the proportion 0.23 mg oxygen perMUmol nitrate. This proportionality was similar to previous results in this laboratory (using different systems), as was the effect of temperature. The mean of two Q10 values in this work was 2.7. PMID- 24233397 TI - Aerobic versus anaerobic metabolism of halogenated anilines by aParacoccus sp. AB - AParacoccus sp. which transforms aniline and different halogen-substituted derivatives under aerobic and anaerobic conditions was isolated from the soil. In experiments with(14)C-ring-labeled 4-chloroaniline, approximately 60% of the radioactive material disappeared from the growth medium after incubation under anaerobiosis within 48 hr, but under aerobic conditions no decrease of radioactivity in the growth medium was observed, although 4-chloroaniline was completely metabolized. Acetylation appears to constitute, especially under aerobic conditions, a major transformation mechanism by the bacterium, since almost 50% of the acetylated compound could be detected and identified if aniline, 2-, 3-, and 4-chloroaniline served as substrate. The formation of different metabolites under aerobic and anaerobic conditions clearly indicates the existence of two separate pathways in the metabolism of aniline compounds depending on the oxygen status of the environment. PMID- 24233398 TI - An enrichment technique for isolation of marine chemotactic bacteria. PMID- 24233399 TI - Synergistic activities of MET/RON inhibitor BMS-777607 and mTOR inhibitor AZD8055 to polyploid cells derived from pancreatic cancer and cancer stem cells. AB - Tyrosine kinase inhibitor BMS-777067 is an inhibitor of RON/MET receptor tyrosine kinases currently under clinical trials. Here, we report the synergistic activity of BMS-777607 in combination with mTOR inhibitor AZD8055 in killing chemoresistant pancreatic cancer and cancer stem cells. Treatment of pancreatic cancer L3.6pl cells with BMS-777607 alone inhibited clonogenic growth and moderately induced apoptotic death. However, BMS-777607 caused extensive polyploidy in L3.6pl cells through inhibition of aurora kinase B activity, independent of RON expression. In contrast, L3.6pl-derived cancer stem cells were highly resistant to BMS-777607-induced growth inhibition and apoptosis. The effect of BMS-777607 on induction of cancer stem cell polyploidy was also weak. BMS-777607-induced polyploidy features a predominant cell population with 8N chromosome content in both L3.6pl and cancer stem cells. These cells also showed decreased sensitivity toward chemotherapeutics by increased survival of IC(50) values in response to doxorubicin, cisplatin, methotrexate, 5-fluorouracial, and gemcitabine. Among a panel of chemical inhibitors that target different signaling proteins, we found that BMS-777607 in combination with mTOR inhibitor AZD8055 exerted synergistic effects on L3.6pl and cancer stem cells. More than 70% of L3.6pl and cancer stem cells lost their viability when both inhibitors were used. Specifically, BMS-777607 in combination with inhibition of mTORC2, but not mTORC1, was responsible for the observed synergism. Our findings demonstrate that BMS-777607 at therapeutic doses exerts inhibitory activities on pancreatic cancer cells but also induces polyploidy insensitive to chemotherapeutics. Combination of BMS-777607 with AZD8055 achieves the maximal cytotoxic effect on pancreatic cancer and cancer stem cells. PMID- 24233400 TI - A simplified culture system to examine soluble factor interactions between mammalian cells. AB - Interactions between different cell types play critical roles in normal development and disease, but remain challenging to analyse. Here, a co-culture system is described that overcomes many of the limitations of existing methods, is simple to construct and modify, and is compatible with standard cellular and molecular assays. PMID- 24233401 TI - [Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics : Part 1: An online survey among German breast care centers.] AB - PURPOSE: Galactography has been used in cases of pathological discharge for decades. Meanwhile other methods, such as high-resolution ultrasound (US) and magnetic resonance mammography (MRM) have been established for modern multimodal breast imaging. A survey among certified German breast care centers aimed to investigate to what extent galactography is currently used and whether newer techniques in multimodal imaging are preferred. MATERIALS AND METHODS: An anonymous online survey was carried out nationwide and open to 342 radiology units in certified German breast care centers. RESULTS: A total of 177 units (52 %) participated in the survey of which 13 % generally do not provide galactography, 33 % conduct a maximum of 5 galactographies per year, 24 % conduct 6-10, 18 % 11-20, 8 % 21-50 and 5 % 51-100. Of the participants 53 % give first priority to US and prefer galactography to MRM in stepwise diagnosis and 32 % prefer MRM to galactography. Only 4 % use galactography initially. CONCLUSION: Currently galactography is no longer a mandatory standard and newer methods are preferred. The evidential value of galactography in comparison to other techniques should be established on the basis of the literature. The second part of this paper will deal with this question. PMID- 24233402 TI - [Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics. Part 2: a systematic review of the literature]. AB - BACKGROUND: The survey results of a previous study showed that galactography is now rarely used in Germany and newer methods are applied. The evidential value of galactography should be established and opposed to the evidential value of ultrasound (US) and magnetic resonance mammography (MRM). MATERIALS AND METHODS: A search was carried out in PubMed and Cochrane involving studies written in English or German. The level of evidence was measured according to the Oxford Centre for Evidence-based Medicine. RESULTS: A total of 19 studies were included, 14 with results on galactography, 10 on US and 5 on MRM. Almost all studies were retrospective with an evidence assigned to level 3b or lower. The results on the diagnostic values showed a very wide range. Because of very variable numbers of cases and consideration of various pathologies, the studies are only comparable to a limited extent. CONCLUSION: Galactography, US and MRM all show a weak level of evidence and no superiority of a particular method can be derived. Therefore, galactography can no longer be considered as a mandatory standard in modern multimodal imaging of the breast. Recommendations for the diagnostic work-up of pathological nipple discharge have to be included in current guidelines and must consider these facts. PMID- 24233403 TI - [Recanalization of thrombosis of the superior vena cava using an Aspirex catheter.] PMID- 24233404 TI - Pseudothrombocytopenia in a neonate due to mother. PMID- 24233405 TI - Symptom positivity is essential for omitting biopsy in children with suspected celiac disease according to the new ESPGHAN guidelines. AB - The aim of this study was to assess the accuracy of serological tests in combination with clinical symptoms for diagnosing celiac disease (CD) according to the new proposed European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. We retrospectively assessed children and adolescents aged 16 months -19 years who were examined for suspicion of CD (n = 345). Evaluation of clinical symptoms and the presence of tissue transglutaminase (anti-TG-IgA) and endomysial antibodies (EMA-IgA) as well as intestinal biopsies was performed in all patients. Human leukocyte antigens (HLAs) were not included. Among 345 biopsied children, 213 (62 %) children had anti-TG titers >10 times the upper limit of normal (ULN) and positive EMA antibodies. Ninety-nine (29 %) children also had symptoms suggestive of CD in addition to EMA positivity and elevated titers of anti-TG >10 times the ULN. In patients who were asymptomatic, but positive for EMA, and had anti-TG antibodies >10 times the ULN, the specificity of tests for Marsh 2-3 was only 85 %, while in symptomatic patients with the same antibodies levels, the specificity was 99 %. Conclusion: Our results reveal that intestinal biopsies could be omitted in 28 % of patients when the new ESPGHAN guidelines are applied. Due to high accuracy of serological tests in combination with clinical symptoms for diagnosis of CD, the new guideline seems to be applicable even without the use of HLA testing. PMID- 24233406 TI - Commentary: Hemostatic net in rhytidoplasty, author Luiz A. Auersvald. PMID- 24233407 TI - Entomopathogenic nematodes associated with essential oil of Lippia sidoides for control of Rhipicephalus microplus (Acari: Ixodidae). AB - In vitro effect of the association of the entomopathogenic nematodes Heterorhabditis bacteriophora HP88 and Heterorhabditis indica LPP1 with the essential oil of Lippia sidoides on engorged females of Rhipicephalus microplus was assessed. Engorged females with homogeneous weights (p >0.05) were divided into six groups of ten ticks each (each female = an experimental unit). In the treated groups, the ticks were exposed to the oil (40 MUl/ml=4%) and nematodes (300 entomopathogenic nematodes (EPNs/tick) separately and also to the nematodes together with the oil, while in the control group, the females were immersed in Tween 80 (3%). All the treatments caused a significant reduction in the egg mass weight (p <0.05). The hatching percentage of larvae was reduced (p <0.05) in the groups treated with H. bacteriophora HP88, H. indica LPP1, and H. bacteriophora HP88 associated with the oil, but in the group treated only with the oil, the hatching of percentage of larvae rate was similar to that of the control group (p >0.05). The percentage of control in the group exposed only to the oil was 50.7%, while in the other treated groups, the percentage of control was greater than 95 %, reaching 100 %in the group treated with H. indica LPP1 associated with the oil. The results of the L. sidoides essential oil in the concentrations tested in association with both H. bacteriophora HP88 and H. indica LPP1 indicate that these combinations can be used to control R. microplus. PMID- 24233408 TI - Characterization of Giardia lamblia genotypes in dogs from Tucson, Arizona using SSU-rRNA and beta-giardin sequences. AB - The objective of this study was to determine if human genotypes of Giardia lamblia could be found in canine companion animals from urban and peri-urban environments in Tucson, Arizona. Canine fecal samples collected from the Humane Society of Southern Arizona between July 2006 and April 2009 were screened for G. lamblia infection using immunofluorescent microscopy and confirmed by polymerase chain reaction (PCR). Of the 672 samples screened, 196 were found positive by IFA and 185 of those positive were successfully amplified through PCR. Sequencing analysis showed samples were primarily of the C or D genotypes (n =154), or showing a mix of the C and D genotypes (n =10). One sample showed a mixed infection of a human genotype (A) and a dog-specific genotype (C). These data are consistent with previous studies showing dog specific genotypes to be dominant in environments where dog-to-dog transmission is likely to occur, and provides further evidence that multiple genes should be targeted for more accurate genotype characterization. PMID- 24233409 TI - Morphologic identification of a new Sarcocystis sp. in the common moorhen (Gallinula chloropus ) (Aves: Gruiformes: Rallidae) from Brolos Lake, Egypt. AB - Sarcocystis species are among the most common and widespread protozoan parasites of mammals and birds. The current study provides the first record of infection with Sarcocystis species in the common moorhens from Brolos Lake, KafrElsheikh province, Egypt. Morphology of the parasite cysts was described using light and transmission electron microscopy. Out of 25 examined birds, sarcocysts were found in neck, thigh, and legs muscles of two birds. The cysts were microscopic and measured 150-650 MUm in length*45-185 MUm in width. Histologically, the sarcocyst wall appeared striated and characterized by the presence of radial spines. Ultrastructurally, it measured 2-4.5 MUm in thickness and had irregularly shaped crowded finger-like villar protrusions that measured 1.5-4 MUm in length and up to 0.4-2 MUm in width with the presence of dense electron ground substance of 200 750 nm thick. Several septa derived from the ground substance were present and divided the cyst into compartments containing both bradyzoites and metrocytes. The bradyzoites were banana-shaped and measured 6-12 * 1-2 MUm with centrally or posteriorly located nuclei. The ultrastructural features of the cyst wall belonged to type 10 cyst wall according the classification of Dubey et al. (1989) and Dubey and Odening (2001). PMID- 24233411 TI - Instrumentation: Quovadis, or new directions. PMID- 24233410 TI - Eosinophil chemotactic chemokine profilings of the brain from permissive and non permissive hosts infected with Angiostrongylus cantonenis. AB - Angiostrongylus cantonensis invasion primarily cause heavy or negligible eosinophic meningitis and meningoencephalitis in the brain of non-permissive and permissive hosts, respectively. Chemokines are effective leukocyte chemoattractants and may play an essential role in mediating eosinophil recruitment in angiostrongyliasis. In the present study, we comparatively analyzed changes in peripheral and CSF eosinophil counts, and expression profilings of eosinophil chemotactic chemokines in A. cantonensis-infected mice (CCL 2, CCL 3, CCL 5, CCL7, CCL 8, CCL 11, CCL 12, CCL 24 and CCL 28) and rats (CCL 2, CCL 3, CCL 5, CCL 11 and CCL 12) were explored at 1, 2, 5, 7, 14, and 21 days post-infection (dpi), and found significantly elevated numbers of eosinophils in blood and CSF of infected mice after 5 dpi, while significant increases of eosinophils in blood and CSF of infected rats were detected after 5 and 14 dpi, respectively. The kinetics of CSF eosinophilia is basically correlated with eosinophil chemotactic chemokine levels in brains of infected animals at each time point. Interestingly, less CSF eosinophils and infiltration of eosinophils in the brain were noted in rats than in mice, though extremely high levels of chemokines were also maintained in the brains of infected rats at 21 dpi. We further described CCL 11 (eotaxin), a previously reported eosinophil chemotactic factor in angiostrongyliasis, was mainly released from activated microglia in mice and rats infected with A. cantonensis. Our results reveal that different complicated chemokine networks mediate recruitment of eosinophils between permissive and non-permissive hosts during A. cantonensis infection, and provide promising targets for clinical treatment of angiostrongyliasis. PMID- 24233412 TI - Surfactant solubilization of hydrophobic compounds in soil and water : II. The role of dodecylsulphate-soil interactions for hexachlorobenzene. AB - The soil/water partition coefficient (Kd) of hexachlorobenzene (HCB) ranged from 220 1/kg to 1800 1/kg for eight soils having a wide range of physico-chemical properties. Kd normalised to soil organic carbon (Koc) was found to be 28000 +/- 4800 1/kg. Anionic surfactant dodecylsulphate (DS) present at concentrations above the critical micellar concentration (CMC) caused reductions in the apparent soil/water partition coefficient (Kd (*)) in the range of 3-26 times for most soils and up to 36-91 times for sandy soils. Below CMC, at environmentally relevant surfactant concentrations, Kd (*) was reduced by a factor of 1-13. For clay and calcareous soils significant adsorption/complexation/precipitation of DS occurred. At the lowest DS concentration this produced a two-fold increase in Kd (*). At increasing DS concentrations this effect was shielded by the solubihzing effect from DS. Monomer (Kmn) and micellar (Kmc) surfactant/water partition coefficients for HCB were determined to be, 980 +/- 190 1/kg and 21000 +/- 1600 1/kg, respectively. PMID- 24233413 TI - Nitro musk compounds genotoxic activity : Genotoxicity testing of nitro musks with the SOS-chromotest and the sister-chromatid exchange test. AB - Five nitro musk compounds are widely used as fragrance ingredients in perfumes, lotions and detergents; as food additives in cigarettes and fish baits, and in such technical products as herbicide formulations and explosives. Several studies identified nitro musk compounds in aquatic environment samples, human milk and fat samples as highly lipophilic and persistent bioaccumulating environmental pollutants. To examine the compounds for genotoxic activity, musk xylene (1-tert. butyl-3, 5-dimethyl-2, 4, 6-trinitrobenzene), musk ketone (4-tert.-butyl-3, 5 dinitro-2, 6-dimethylacetophenone), musk ambrette (l-tert.-butyl-4-methyl-6 methoxy-3, 5-dinitrobenzene), musk moskene (l, 1, 3, 3, 5-pemamethyl-4, 6-di nitroindane) and musk tibetene (1-tert.-butyl-3, 4, 5-trimethyl-2, 6 dinitrobenzene) were tested for SOS inducing potency in the SOS chromotest with E. coli PQ37 and for sister-chromatid exchange inducing activities in human lymphocytes in vitro both in the presence and absence of an exogenous metabolizing system from rat liver S9-Mix. Nitro musks revealed no genotoxicity either in the SOS chromotest with E. coli PQ37 or in the sister-chromatid exchange test with human lymphocytes. PMID- 24233414 TI - The internet: LISTSERV - decide to subscribe. PMID- 24233415 TI - Ozone and grosswetterlagen : Analysis for the Munich metropolitan area. AB - Meteorological conditions have a decisive impact on surface ozone concentrations. In this study, an empirical model is used to explain the interdependence of ozone and grosswetterlagen. Different meteorological parameters such as air temperature, global solar radiation, relative humidity, wind direction and wind speed are used. Additional nitric oxide (NO) was taken as a representative for the emission situation and ozone maximum of the preceding day in order to evaluate the development of the photochemical situation.The dataset includes data collected over a period of three years (1992-1994) from three stations outside of Munich and one in the center of Munich.All values become variables by calculating means, sums or maxima of the basic dataset consisting of half-hour means. Seasonal periodicity of data is detected with Fourier analysis and eliminated by a division method after computing a seasonal index.The dataset is divided into three different grosswetterlagen groups, depending on main wind direction. One mostly cyclonic (westerly winds), one mixed (alternating winds) and one only anticyclonic (easterly winds). The last is completed with one summertime group including values from April to August.Factor analysis is performed for each group to obtain independent linear variable combinations. Overall, relative humidity is the dominant parameter, a typical value indicating meteorological conditions during a grosswetterlage.Linear multiple regression analysis is performed using the factors obtained to reveal how the ozone concentrations are explained in terms of meteorological parameters and NO. The results improve from cyclonic to anticyclonic grosswetterlagen in conformance with the increasing significance of photochemistry, indicated by the high solar radiation and high temperature, and the low relative humidity and low wind speed. The explained variance r(2) reaches its maximum with more than 50 % of the time in Munich center.This empirical model is applicable to the forecasting of local ozone maximum concentrations with a total standard error deviation of 8.5 to 12.8 % and, if ozone concentrations exceed 80 ppb, with a standard error deviation of 5.4 to 9.5 %. PMID- 24233416 TI - Predicting ozone levels : A statistical model for predicting ozone levels in the Shuaiba Industrial Area, Kuwait. AB - This paper presents a statistical model that is capable of predicting ozone levels from precursor concentrations and meteorological conditions during daylight hours in the Shuaiba Industrial Area (SIA) of Kuwait. The model has been developed from ambient air quality data that was recorded for one year starting from December 1994 using an air pollution mobile monitoring station. The functional relationship between ozone level and the various independent variables has been determined by using a stepwise multiple regression modelling procedure. The model contains two terms that describe the dependence of ozone on nitrogen oxides (NOx) and nonmethane hydrocarbon precursor concentrations, and other terms that relate to wind direction, wind speed, sulphur dioxide (SO2) and solar energy. In the model, the levels of the precursors are inversely related to ozone concentration, whereas SO2 concentration, wind speed and solar radiation are positively correlated. Typically, 63 % of the variation in ozone levels can be explained by the levels of NOx. The model is shown to be statistically significant and model predictions and experimental observations are shown to be consistent. A detailed analysis of the ozone-temperature relationship is also presented; at temperatures less than 27 degrees C there is a positive correlation between temperature and ozone concentration whereas at temperatures greater than 27 degrees C a negative correlation is seen. This is the first time a non-monotonic relationship between ozone levels and temperature has been reported and discussed. PMID- 24233417 TI - Global total ozone dynamics : Impact on surface solar ultraviolet radiation variability and ecosystems Part II: Dynamics of atmospheric chemical composition: The role of remote sensing Part I: Global ozone dynamics and environmental safety (ESPR 3/96, pp. 153-157). AB - A review has been made recently studying global total ozone changes (including stratospheric and troposphere components), as well as biologically active surface solar ultraviolet (UV-B) radiation variations on the basis of satellite and conventional surface observations (Kondratyev and Varotsos, Part I). In the aforementioned review, relevant impacts on terrestrial and aquatic ecosystems, as well as on biochemical cycles and man, have been discussed. Special attention has been paid to the analysis of observed and potential impacts of enhanced UV-B radiation on biogeochemical cycles and the chemical composition of the atmosphere. In this context, possibilities remote sensing techniques applications aimed at obtaining more complete information on atmospheric concentrations of various trace gases determining the ozone content have been considered in the present paper.An overview of the ozone issues is given including the following aspects: 1. The impact of tropospheric ozone on climate as a greenhouse gas (GHG), 2. Solar activity effects on TO and ozone concentration vertical profiles in both the troposphere and stratosphere (in cases of solar radiation absorption by the stratosphere, an unexpected problem arises via a coupling between processes of increased absorption due to "bursts" of solar activity and an enhanced destruction of ozone molecules due to the same increase resulting in weakening UV radiation absorption) and 3. Surface ozone concentration variations under conditions of polluted urban atmospheres which lead to episodes of photochemical smog formation (dangerous for human health). PMID- 24233418 TI - Increasing concentrations of CO and O3 rising deforestation rates and increasing troposheric carbon monoxide and ozone in Amazonia. AB - Increasing carbon monoxide and ozone concentrations have been observed in the lower troposphere of the Brazilian Amazon region in recent years (1989-1995). Carbon monoxide and ozone have been measured in the region continuously; from observations at a single site and many sporadic field missions, there is a clear indication that the chemical activity in the troposphere is growing, with increasing concentrations especially during the dry season. On the other hand, the most recent deforestation assessment by the Brazilian Government, performed by the Instituto Nacional de Pesquisas Espaciais (INPE) using Landsat data, shows yearly rates rising from the 11,130 km(2) year(-1) minimum of the 1990/91 survey, to 13,786 km(2) year(-1) for the 1991/92 period, and 14,896 km(2) year(-1) for the period 1992/94. It is argued that the increase in deforestation/biomass burning activities in "Amazonia" have produced larger carbon monoxide and ozone concentrations in the lower atmosphere. PMID- 24233419 TI - Ozone exposure : Areas of potential ozone risk for selected tree species in Austria. AB - Increased tropospheric ozone concentrations cause damage to both human health and the environment. To assess the exposure of forest areas and selected tree species to ozone, it is necessary to calculate the ozone exposure distribution. The present article describes the application of an ozone interpolation model to the calculation of the ozone exposure distribution in combination with forest inventory data.The exposure of forest regions to ozone was assessed by means of an AOT40 map (accumulated ozone exposure over a threshold of 40 ppb). The calculation was performed by hourly running of the model during the summer term and accumulation of the patterns that exceeded 40 ppb.The exposure of the primary Austrian tree species to ozone can be assessed due to the spatial relation of ozone exposure and tree species patterns. This spatial relation also allows the verification of assumptions concerning ozone-related tree damage. PMID- 24233420 TI - Airborne lipophilic pollutants in pine needles. AB - Many environmental contaminants known today are semivolatile organic compounds (SOC) and are present in the atmosphere. Airborne SOC are taken up and enriched by the epicuticular wax that covers leaves of higher plants. The purpose of the present work was to use pine needles 1) to map the distribution of airborne SOC in Europe, 2) to identify source regions, and 3) to identify hitherto unknown anthropogenic and/or natural substances. Some of the results were a confirmation of a suspected release of DDT in the former East Germany, high levels of pentachlorophenol were noted in Scandinavia, hexachlorocyclohexanes were higher in southern than in northern Europe, whereas PCB and hexachlorbenzene were rather evenly distributed throughout Europe. Elemental sulphur was identified as a previously unknown natural substance in higher plants. PMID- 24233421 TI - Applications of experts' judgement to derive structure-biodegradation relationships. AB - The experts' judgement data on microbial degradation were used to develop the first general QSAR biodegradability model (Boethling and Sabljic, 1989) which is composed of a set of structural descriptors and a set of quantitative rules. Its evaluation and validation with experimental biodegradation data clearly show that the developed model gives a realistic and reliable account of structurebiodegradability relationship for organic chemicals. The same set of experts judgement data was used to develop structure-biodegradation rule by the application of an inductive machine learning method. An improved structure biodegradation rule was derived from a larger training set of 160 chemicals, i.e. the combined experts' judgement and evaluated experimental biodegradation data. This rule has good predictive ability and discloses logical dependencies between structural features that have a strong influence on biodegradation of organic chemicals. Thus, the understanding of biodegradation processes will benefit from developed rule. PMID- 24233422 TI - Managing soil remediation problems. AB - Soil remediation has only a short history but the problem addressed is a significant one. Cost estimates for the clean-up of contaminated sites in the European Union and the United States are in the order of magnitude of 1,400 billion ECU. Such an enormous operation deserves the best management it can get. Reliable cost estimations per contaminated site are an important prerequisite. This paper addresses the problems related to site-wise estimations.When solving soil remediation problems, we have to deal with a large number of scientific disciplines. Too often solutions are presented from the viewpoint of only one discipline. In order to benefit from the combined disciplinary knowledge and experience, we think that it is necessary to describe the interrelations between these disciplines. This can be realized by developing an adequate model of the desired process which enables to consider and evaluate the essential factors as interdependent components of the total system.The resulting model provides a binding paradigm to the contributing disciplines which will result in improved efficiency and effectivity of the decision and the cost estimation process. In the near future, we will release the "Biosparging and Bioventing Expert Support System", an expert support system for problem owners, consultants and authorities dealing with the design and operation of a biosparging and/or a bioventing system. PMID- 24233423 TI - The revised Swiss environmental protection law - Main innovations. PMID- 24233424 TI - ECO-Informa '96 : Global networks for environmental information A conference held from November 4-7 at Lake Buena Vista, Florida, USA. PMID- 24233425 TI - Problem gambling and policy advice: The mutability and relative effects of structural, associational and attitudinal variables. AB - Research on gambling has the double mandate of public service and the advancement of science. This paper is meant to carry forward that mandate. Latent in research on the causes of problem gambling is the policy insight that these causes represent different types of phenomena and are unequally mutable to practitioners' efforts to prevent and/or treat problem gambling. By making the issue of mutability manifest in research, findings from research would have more policy relevance and practical import. Data from a 1989 Iowa survey on lottery play and problem gambling are analyzed to illustrate this point. 1,226 respondents were contacted by phone and phone interviews were completed with 1,011 of these 1,226 eligible respondents. With multiple regression, we assessed the contributions of mutable and immutable variables to the explained variance in problem gambling. The results show mutable correlates explain enough variance in problem gambling to recommend their consideration in treatment/prevention. The results also suggest a social as well as a psychological etiology to problem gambling. Future research should, however, do a more complete comparison of social and psychological causes of problem gambling. PMID- 24233426 TI - The role of subjective mood states in the maintenance of fruit machine gambling behaviour. AB - Explanations involving the etiology of pathological gambling have tended to emphasize psychosocial factors. However, the possibility that psychobiological factors are important should not be ruled out. Two currently researched psychobiological approaches to gambling involve the role of (i) arousal and (ii) depression. A study analyzing the subjective mood variables of 60 gamblers (44 males and 16 females; mean age 23.4 years) using self report measures was carried out in an attempt to identify which mood states are critical to gambling maintenance. Results indicated that regular and pathological gamblers experienced more depressive moods before playing and that regular and pathological gamblers experienced significantly more excitement during gambling than non regular gamblers. These results are discussed in relation to contemporary literature regarding the roles of arousal and depression in the maintenance of gambling behaviour. PMID- 24233427 TI - Legalized gambling and its impacts in a central Minnesota vacation community: A case study. AB - The economic and social effects of legalized gambling in a Minnesota community were studied (1) to inform the state's citizens and decision-makers of the community impacts of legalized gambling, particularly the cumulative community revenue loss, (2) to gather comparative data in a geographically and economically distinct area to determine the extent to which regional gambling rates and revenue losses vary, and (3) to refine existing research methods. The community and the types of gambling available are described. Data on gambling expenditures were obtained from various state agencies. Lottery and casino winners were interviewed to discover how their winnings were distributed. Annual (1991) player losses, profit margins, taxes, and resulting economic and social impacts are discussed. The most consequential findings are estimates of annual player losses ($3.3 million; $205 per capita) and community revenue losses ($2.2 million; $138 per capita). Per capita lottery and charitable gambling player losses were 9.4% lower than those of a community studied earlier; per capita community revenue losses were 7.6% lower. Research methods developed in this study provided more reliable estimates than those used previously. Suggestions are offered to increase reliability for future studies. PMID- 24233428 TI - Monitoring adolescent gambling in Minnesota. AB - Youth gambling was investigated in a prospective sample of 532 Minnesota adolescents and young adults. Of particular interest was the possible impact among the study sample of a recent state lottery and of reaching the legal age for gambling on changes in the rate and type of gambling. Overall rates of gambling involvement and pathological gambling did not change across the 1.5 year interval. However, a preference for certain types of gambling activities (e.g., lottery, casino machines) significantly increased, whereas more informal and unregulated games (e.g., betting on games of personal skill) significantly decreased. Also, access to gambling activities by underage youths was high, suggesting the need for tighter controls of legalized games and greater awareness of this problem by the gaming industry and public health officials. PMID- 24233429 TI - Effects of accuracy feedback versus monetary contingency on arousal in high and low frequency gamblers. AB - This study examined the effects on arousal of feedback regarding prediction accuracy without monetary gain or loss versus accuracy feedback combined with monetary contingency involved in most gambling. Physiological and subjective arousal was assessed in frequent (n = 35; 16 females) and infrequent gamblers (n = 35; 16 females) during participation in a laboratory gambling game. Both samples consisted of undergraduate student volunteers. In one condition, subjects gambled money on their predictions about a sequence of events, hence receiving both feedback and monetary outcome. In the other condition, only feedback about accuracy was provided, with no money wagered. Arousal was greater for both groups during actual gambling than in the feedback only condition. Across both conditions, frequent gamblers exhibited greater arousal than did infrequent gamblers. There were, however, no significant Group X Condition interactions. These results suggest that actual monetary contingency rather than accuracy feedback alone is most motivating in gambling. Methodological limitations possibly related to the lack of Group X Condition interactions were discussed. PMID- 24233430 TI - Cognitive and behavioral therapies for pathological gambling. AB - The purpose of this paper is to provide an overview of behavioral and cognitive treatment approaches in the management of pathological gambling disorders. Disappointingly, the literature to date contains only one controlled outcome study in which two differing behavioral techniques were compared. Although research in general has focussed on identifying the nature of cognitive distortions in gambling, findings from these studies have not been systematically translated into treatment programs. It is concluded that methodological limitations including small sample size, absence of control groups, multiple concurrent interventions and poorly defined outcome criteria preclude conclusive statements to be drawn regarding the active ingredient of either behavioral or cognitive strategies. The program offered within the Impulse Disorders Research Centre is outlined. PMID- 24233431 TI - Differences in preferred level of arousal in two sub-groups of problem gamblers: A preliminary report. AB - Twelve problem poker machine players and thirteen horse race gamblers (20 males and 5 females; age range 28-69) completed a series of questionnaires which assessed levels of anxiety, their preferred state of arousal and their motivations to gamble. As predicted, problem poker machine gamblers were found to be more anxious and reported avoiding arousal more frequently than the horse race gamblers. Alternately, problem horse race gamblers were found to prefer heightened levels of arousal and appeared to gamble to achieve these optimal levels of arousal. However, there was no difference between the groups on proneness to boredom. The present results provide evidence which is consistent with the Reversal theory and its application to the field of problem gambling. PMID- 24233432 TI - "Postmodern" Las Vegas and its effect on gambling. PMID- 24233433 TI - Editorial Comment: Symposium: 2013 Knee Society Proceedings. PMID- 24233435 TI - Association of lymphotoxin alpha polymorphism with type 1 diabetes in a Tunisian population. AB - We investigated the association of the lymphotoxin (LT)-alpha gene polymorphism +249A/G with type 1 diabetes. The distribution of genotypes of the LT-alpha +249A/G single nucleotide polymorphism (SNP) was assessed in 115 diabetic patients and 123 normoglycemic control subjects, using PCR-restriction fragment length polymorphism analysis. Among unselected patients, the SNP was significantly associated with increased risk of diabetes (chi2 = 8.44, p = 0.014) and was found to be more pronounced among female (chi2 = 8.37, p = 0.02) than male (chi2 = 6.11, p = 0.047) patients. A significant association was detected between LT-alpha +249A/G and increased risk of diabetes, in particular for young onset patients (chi2 = 6.92, p = 0.031). Moreover, we reported significant differences in levels of HbA1c, triglycerides, alanine transaminase, and anti glutamic acid decarboxylase-65 among alleles. Additional studies with extended patient age groups and different ethnicities are needed to confirm our findings. PMID- 24233434 TI - The distinct roles of anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1) in fluid and electrolyte absorption in the murine small intestine. AB - The mixing of gastric and pancreatic juice subjects the jejunum to unique ionic conditions with high luminal CO2 tension and HCO3 - concentration. We investigated the role of the small intestinal apical anion exchangers PAT-1 (Slc26a6) and DRA (Slc26a3) in basal and CO2/HCO3 --stimulated jejunal fluid absorption. Single pass perfusion of jejunal segments was performed in anaesthetised wild type (WT) as well as in mice deficient in DRA, PAT-1, Na+/H+ exchanger 3 (NHE3) or NHE2, and in carbonic anhydrase II (CAII). Unbuffered saline (pH 7.4) perfusion of WT jejunum resulted in fluid absorption and acidification of the effluent. DRA-deficient jejunum absorbed less fluid than WT, and acidified the effluent more strongly, consistent with its action as a Cl /HCO3 - exchanger. PAT-1-deficient jejunum also absorbed less fluid but resulted in less effluent acidification. Switching the luminal solution to a 5 % CO2/HCO3 buffered solution (pH 7.4), resulted in a decrease in jejunal enterocyte pHi in all genotypes, an increase in luminal surface pH and a strong increase in fluid absorption in a PAT-1- and NHE3- but not DRA-, CAII, or NHE2-dependent fashion. Even in the absence of luminal Cl-, luminal CO2/HCO3 - augmented fluid absorption in WT, CAII, NHE2- or DRA-deficient, but not in PAT-1- or NHE3-deficient mice, indicating the likelihood that PAT-1 serves to import HCO3 - and NHE3 serves to import Na+ under these circumstances. The results suggest that PAT-1 plays an important role in jejunal Na+HCO3 - reabsorption, while DRA absorbs Cl- and exports HCO3 - in a partly CAII-dependent fashion. Both PAT-1 and DRA significantly contribute to intestinal fluid absorption and enterocyte acid/base balance but are activated by different ion gradients. PMID- 24233436 TI - Three novel SNPs in the coding region of the bovine MC3R gene and their associations with growth traits. AB - The involvement of melanocortin-3 receptor (MC3R) is well recognized in the regulation of feeding efficiency, body weight, and energy homeostasis. The objective of this study was to investigate the associations between MC3R gene polymorphisms and growth traits. Three novel SNPs (c.24C->T, c.220T->A, c.734G >C) and five haplotypes were identified in 234 Xiangxi cattle. The associations between MC3R gene polymorphisms and growth traits indicated that the individuals with TT and AT genotypes maintained higher body weight than those with the AA genotype at the c.220T->A locus (P < 0.05). The animals with GG and CG genotypes had higher heart girth and body weight than those with the CC genotype at c.734G >C (P < 0.05). The animals with H3H3 and H2H3 haplotype combinations had higher body weight than those with other haplotype combinations (P < 0.05). The results suggest that these SNPs in the MC3R gene might be useful genetic markers for marker-assisted selection and cattle breeding. PMID- 24233437 TI - A comparison of antioxidant activity of Korean White and Red Ginsengs on H2O2 induced oxidative stress in HepG2 hepatoma cells. AB - The aim of this study was to determine and compare the preventive effect of Korean White Ginseng and Red Ginseng on oxidative stress in H2O2-treated HepG2 cells. The roots of ginseng were extracted with 70% methanol and partitioned with butanol to obtain saponin fractions, which have been known as bioactive constituents of ginseng. 2',7'-Dichlorofluorescein diacetate (DCF-DA) assay and malondialdehyde (MDA) content were measured for evaluating intracellular reactive oxygen species (ROS) generation. Also, mRNA expressions and activities of antioxidant enzymes were analyzed to determine the antioxidant activity of saponin or non-saponin fractions of ginsengs. According to DCF-DA assay, H2O2 induced MDA release and ROS generation were significantly reduced by treatment with saponin fractions of white and red ginseng roots. Also, saponin fractions increased effectively intracellular antioxidant enzyme activities including catalase, glutathione peroxidase and superoxide dismutase in H2O2- treated HepG2 hepatoma cells. In general, red ginseng was more effective than white ginseng for reducing oxidative stress. These results indicate that administration of red ginseng may certainly contribute relatively stronger than white ginseng to prevent from damaging liver function by oxidative stress. PMID- 24233438 TI - Ammonia distribution and excretion in fish. AB - This paper reviews the literature concerning ammonia production, storage and excretion in fish. Ammonia is the end product of protein catabolism and is stored in the body of fish in high concentrations relative to basal excretion rates. Ammonia, if allowed to accumulate, is toxic and is converted to less toxic compounds or excreted. Like other weak acids and bases, ammonia is distributed between tissue compartments in relation to transmembrane pH gradients. NH3 is generally equilibrated between compartments but NH4 (+) is distributed according to pH. Ammonia is eliminated from the blood upon passage through the gills. The mechanisms of branchial ammonia excretion vary between different species of fish and different environments, and primarily involves NH3 passive diffusion and NH4 (+)/Na(+) exchange. Water chemistry near the gill surface may also be important to ammonia excretion, but a more accurate measurement of the NH3 gradient across the gill epithelium is required before a more detailed analysis of NH3 and NH4 (+) excretion can be made. PMID- 24233439 TI - Androgen levels and erythrocytosis in maturing brown trout,Salmo trutta L. AB - The number of circulating erythrocytes was monitored in two strains of brown trout during the spawning season. Erythrocyte numbers were significantly elevated in mature male fish of both strains compared with mature females or immature fish. This period of erythrocytosis coincided with elevated plasma 11 ketotestosterone levels in mature male fish, was out of phase with the testosterone peak in males and was not observed in females despite high levels of plasma testosterone. The results are discussed with reference to the control of erythropoiesis in higher vertebrates. PMID- 24233440 TI - Total and free thyroid hormones in plasma of tropical marine teleost fish. AB - Plasma levels of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) and the percentage of plasma T4 and T3 present in the free (dialyzable) form (%FT4 and %FT3) were measured in 16 species (11 families) of tropical marine teleosts from an inshore Barbados reef. Mean plasma T4 varied from 0.2 ng/ml to 42 ng/ml; mean plasma T3 varied from < 0.2 ng/ml to 50 ng/ml. The highest T4 and T3 levels were recorded in parrot-fish and the lowest levels in filefish. The %oFT4 and %FT3 varied from 0.05-3.41%. Estimated levels of plasma free T4 and free T3 levels ranged from 0.4-466 pg/ml. The extremely wide inter- and intra-species ranges in levels of free T4 and T3 do not support a previous suggestion, based on temperate freshwater salmonid species, that free T4 and T3 levels in fish may fall within a relatively range narrow comparable to that of homeothermic vertebrates. PMID- 24233441 TI - Absorption, body distribution, and excretion of dietary zinc by rainbow trout (Salmo gairdneri). AB - Rainbow trout (Salmo gairdneri) were held in metabolizable energy chambers at Standard Environmental Temperature (15 degrees C) for 72h following a single feeding of a semi-purified test diet containing tracer quantities of a radioisotope of zinc ((65)Zn) and different combinations of dietary calcium level and zinc source. Gill wastes, urine, and feces were separately collected. After 72h, the fish were killed, and samples of the following tissues removed: eyes, skin, muscle, blood, bone, liver, bile, kidney, gill, spleen, stomach, pyloric caeca, intestine, gonad, and remaining carcass. Radioactivity in the tissues and wastes was determined and the body distribution of the ingested zinc was quantified. Approximately 58% of the administered dose of(65)Zn was recovered. Of the recovered dose, 43.2% was present in the gastro-intestinal tract, 27% in the feces, 14% in the gill water, 16% in the body of the fish, and less than 1% in the urine. Of individual tissues, the gill, liver, kidney, and spleen had concentrations of(65)Zn higher than blood, while the remaining tissues had lower concentrations. Body and tissue levels were increased but not significantly by feeding(65)Zn as an amino acid chelate, compared to feeding as inorganic(65)Zn, while dietary calcium level had no effect. The results of this study indicate that the gills play a major role in excretion of dietary zinc, while the urine plays a minor role. PMID- 24233442 TI - Screening for organic acids in fish tissues with special reference to the distribution of taurine inRutilus rutilus L. AB - A liquid chromatographic method for rapid profiling of some organic acids and other compounds of physiological interest in fish tissues is presented. The method provides the detection of alpha-ketoglutaric, malic and pyruvic acid and is optimized for the quantitation of citric, phosphoric, succinic, lactic and fumaric acids, as well as glucose and especially taurine. These substances were separated in a single analytical run on a cation exchange column with dilute sulfuric acid as the elutant. The effluent was monitored by a refractive index or an UV detector at 208 nm wavelength. Resolution was satisfactory. No further treatment was found to be necessary when samples were deproteinized with perchloric acid. Taurine (2-aminoethansulfonic acid), not previously described in the roach (Rutilus rutilus L.), occurs in considerable amounts in red and white muscle and heart tissue. However, it is also present in all other tissues. PMID- 24233443 TI - Distribution and properties of lactate dehydrogenase isoenzymes in red and white muscle of freshwater fish. AB - The distribution and kinetics of LDH isoenzymes in red and white muscles of 5 species of salmonids, 4 species of cyprinids and one coregonid species were studied. In all species the white muscles are characterized by the occurrence of only the most cathodic isoenzymes, or groups of isoenzymes. The red muscles contained either the full set of isoenzymes (cyprinids) or a selection in which the anodic forms dominated (salmonids, coregonid). The most striking difference between the two types of muscle was met inCoregonus sp. The temperature profiles of pyruvate affinity are similar in all species of fish studied. On the other hand, Km(pyr) values and degree of pyruvate inhibition are closely related and vary greatly with temperature, with the taxonomic position (and thus biology) of the species, and with electrophoresic mobility of the isoenzyme. Highest affinity and strongest inhibition occurred in the anodic (H4) isoenzymes of cyprinids at low temperature; lowest affinity and zero inhibition in the cathodic isoenzymes (Malpha4 -> Mbeta4) of salmonids and coregonids at high temperature. In salmonids the more recently duplicated loci of the M-group of isoenzymes possess identical Km values at all temperatures, whereas the two older M and H loci differ greatly in this respect. Thus the more recent duplication of LDH loci in salmonids and coregonids may be seen as a mechanism by which the tetramers required for LDH activity can be constructed from more closely related subunits than are provided by the older M and H loci.Some problems in connection with the determination of the kinetic constants of the lactate oxidase reaction are discussed and it is suggested that an alkaline, pyruvate trapping system provides conditions which are more realistic than those of other assay systems. The Km(lactate) values found are in the biological range and, at 20 degrees C, provide further circumstantial evidence that the red muscles of fish should be capable of oxidizing the lactate produced by the white muscles during strenuous exercise. At 4 degrees C the Km(lactate) values are abnormally high in all muscle preparations and thus are not correlated with the Km(pyruvate) values which are lowest at this temperature. PMID- 24233444 TI - The chemical basis of host-plant recognition in a specialized bee pollinator. AB - Many pollinators specialize on a few plants as food sources and rely on flower scents to recognize their hosts. However, the specific compounds mediating this recognition are mostly unknown. We investigated the chemical basis of host location/recognition in the Campanula-specialist bee Chelostoma rapunculi using chemical, electrophysiological, and behavioral approaches. Our findings show that Ca. trachelium flowers emit a weak scent consisting of both widespread and rare (i.e., spiroacetals) volatiles. In electroantennographic analyses, the antennae of bees responded to aliphatics, terpenes, aromatics, and spiroacetals; however, the bioassays revealed a more complex response picture. Spiroacetals attracted host-naive bees, whereas spiroacetals together with aliphatics and terpenes were used for host finding by host-experienced bees. On the intrafloral level, different flower parts of Ca. trachelium showed differences in the absolute and relative amounts of scent, including spiroacetals. Scent from pollen-presenting flower parts elicited more feeding responses in host-naive bees as compared to a scentless control, whereas host-experienced bees responded more to the nectar presenting parts. Our study demonstrates the occurrence of learning (i.e., change in the bee's innate chemical search-image) after bees gain foraging experience on host flowers. We conclude that highly specific floral volatiles play a key role in host-flower recognition by this pollen-specialist bee, and discuss our findings into the broader context of host-recognition in oligolectic bees. PMID- 24233446 TI - Giant gluteal lipoma presenting as a sciatic hernia. AB - BACKGROUND: Sciatic hernia is considered to be the rarest hernia of pelvic floor with less than one hundred reports published worldwide. Lipoma in the hernia sac is even more unique pathology with only few cases reported in the literature. We report a case of gluteal lipoma protruding into pelvis, displacing rectum with bladder and presenting as a sciatic hernia. CASE PRESENTATION: A 53-year-old male presented with an expanding, slightly reducible, right gluteal painful mass, back pain, dull pressure in lower abdomen and perianal region radiating to the right buttock, urgent urination and defecation. Lower back pain lasts for more than 7 years, other symptoms-6 months. No spinal pathology was found on X-ray. On examination patient seemed well nourished, BMI 29, abdomen was soft, without palpable masses or signs of peritonitis. Digital rectal examination showed no pathology. There was a reducible lump on the lateral side of right gluteus. Computer tomography (CT scan) demonstrated a large intra- and extra-pelvic fatty mass traversing the greater sciatic foramen. The tumor was surgically removed through lower middle laparotomy approach. Subsequent pathological examination revealed lipoma. The patient recovered uneventfully, was discharged 8 days later. MRI scan was advised following 1 year after the surgery. CONCLUSION: The presence of a gluteal mass should always suggest the possibility of a sciatic hernia. PMID- 24233447 TI - Free energy barriers for CO2 and N2 in zeolite NaKA: an ab initio molecular dynamics approach. AB - Ab initio Molecular Dynamics (AIMD) is used with spatial constraints to estimate the free energy barriers of diffusion for CO2 and N2 gas molecules in zeolite NaA and KA. We investigate the extent to which the diffusion of these gas molecules is hindered, in the two separate cases of a smaller Na(+) ion or a larger K(+) ion blocking the 8-ring pore window. In contrast to classical Molecular Dynamics, AIMD performs these computations accurately and unbiased in the absence of empirical parameterization. Our work has resulted in stable and reliable force profiles. The profiles show that the larger K(+) ion effectively blocks the passage of both CO2 and N2 molecules while the smaller Na(+) ion will allow both molecules to pass. These results are a quantitative demonstration of the concept of pore blocking where we compute the effect, which the size of the respective cation occupying the pore window has on diffusive properties of each gas molecule. Hence, this effect can be altered through ion exchange to fine-tune the functionality of a specific zeolite as a molecular sieve. PMID- 24233445 TI - Peramine and lolitrem B from endophyte-grass associations cascade up the food chain. AB - Endophytic fungi in cool-season grass species produce herbivore-toxic alkaloids, which are assumed to harm higher trophic levels along food chains. Previous studies have shown fitness disadvantages for higher trophic levels that feed on aphids that were exclusively reared on perennial ryegrass (Lolium perenne) infected with the endophytic fungus Neotyphodium lolii. However, it is unknown whether the alkaloids produced by the fungus-grass association can be assimilated by plant sap-sucking insects like aphids. Using an ultra high performance liquid chromatography method combined with mass spectrometry, we provide the first evidence that the alkaloids peramine and lolitrem B are present in aphids (Rhopalosiphum padi) and in aphid predators when the aphids are reared on endophyte-infected grass. We conclude that alkaloids can enter the plant sap of the grass and are responsible for longer pupal stages of the ladybird Harmonia axyridis and for fitness disadvantages of aphids and their predators as shown in previous studies. PMID- 24233448 TI - Consumption of Noncommercial Alcohol among Alcohol-Dependent Patients. AB - This study explores types of alcohol and surrogates consumed, patterns of consumption, and reasons behind noncommercial alcohol consumption among alcohol dependent patients in Belarus. The study was conducted in the Belarusian city Grodno in 2012 with 223 alcoholics admitted to narcological clinic using structured interviews. The results suggest that at least 20.2% of alcohol dependent patients regularly consume samogon and 11.8% of patients use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that, according to quality criteria, samogon exceeds licensed vodka is the main motive for its consumption. The results of this study suggest the existence of the problem of consumption of noncommercial alcohol among alcohol dependent patients in Belarus. PMID- 24233449 TI - Quenching interactions and nonexponential decay: tryptophan 138 of bacteriophage T4 lysozyme. AB - Site-directed mutagenesis has been used to prepare variants of bacteriophage T4 lysozyme that contain only one tryptophan residue at position 138 and to change the residues in the immediate environment of this buried residue. Replacement of glutamine-105 by alanine results in a 2.7-fold increase in fluoresence quantum yield and converts the fluorescence decay from a highly nonexponential form to a single-exponential decay. This is atributed to electron transfer quenching of tryptophan-138 fluorescence by glutamine-105. Replacemeent of alanine-146 by threonine results in a 1.6-fold decrease in fluorescence intensity, indicating enhanced quenching by glutamine-105; replacement of glutamine-105 by alanine in this species results in a 5-fold in crease in fluorescence intensity. The interpretation of the nonexponential decay of the glutamine-105-containing species is discussed in terms of reversibility of the quenching process. PMID- 24233450 TI - Steady-state fluorescence and phosphorescence spectroscopic studies of bacterial luciferase tryptophan mutants. AB - Bacterial luciferase, which catalyzes the bioluminescence reaction in luminous bacteria, consists of two nonidentical polypeptides, alpha and beta. Eight mutants of luciferase with each of the tryptophans replaced by tyrosine were generated by site-directed mutagenesis and purified to homogeneity. The steady state tryptophan fluorescence and low-temperature phosphorescence spectroscopic properties of these mutants were characterized. In some instances, mutation of only a single tryptophan residue resulted in large spectral changes. The tryptophan residues conserved in both the alpha and the beta subunits exhibited distinct fluorescence emission properties, suggesting that these tryptophans have different local enviroments. The low-temperature phosphorescence data suggest that the tryptophans conserved in bot the alpha and the beta subunits are not located at the subunit interface and/or involved in subunit interactions. The differences in the spectral properties of the mutants have provided useful information on the local environment of the individual tryptophan residues as well as on the quaternary structure of the protein. PMID- 24233451 TI - Study ofL-tryptophan corepressor binding to mutatedE. coli tryptophan repressor proteins by optically detected triplet-state magnetic resonance. AB - Phosphorescence and optically detected magnetic resonance (ODMR) measurements have been carried out on the tryptophan (Trp) residues ofEscherichia coli Trp repressor protein (W Rep) and its two single Trp-containing mutants, W19F and W99F. The enhanced resolution afforded by the W19F and W99F mutants allowed us to characterize the triplet state of boundL-Trp corepressor using phosphorescence wavelengt-selected ORMR spectroscopy. We find that at 77 K the 0,0 band peak wavelength ofL-Trp is shifted from 405.5 nm in the aqueous solvent to ca. 410 nm when bound to the corepressor binding site. This red shift of the phosphorescence along with a corresponding increase in the zero-field splittingE value and narrowing of the ODMR linewidth characterize a binding site that is less polar, as well as more polarizable and homogeneous, than the aqueous solvent. This conclusion is in agreement with the X-ray crystallographic structure of the holorepressor protein that places the indole chromophore of the bound corepressor in a cleft in which it is sandwiched by the side chains of arginines 54 and 84. PMID- 24233452 TI - Stopped-flow fluorescence studies of the interaction of a mutant form of cytochrome b5 with lipid vesicles. AB - Cytochrome b5 binds spontaneously to lipid vescles and also self-associates in aqueous solution. Two mutant proteins have been generated, one has a self association constant which is less than that of the native protein, while the other has a larger self-association constant. All three proteins have Trp in the membrane-binding domain but as aqueous solutions of these proteins contain differing amounts of monomeric protein, the kinetics of fluorescence enhancement, when the proteins are mixed with lipid vesicles, are complex. Similar complex kinetics are seen when the Trp are quenched by the addition of bromolipid vesicles. The mutant which has Trp 108 and 112 both replaced by Leu does not self associate and shows monoexponential stopped-flow fluorescence kinetics. Identical rate constants are seen with this mutant for fluorescence enhancement by POPC and fluorescence quenching by three bromolipids with bromines at the 6,7-, 9,10-, and 11,12-positions of thesn-2 acyl chain. This rate constant is only 1% of the calculated collisional rate constant and it is suggested that the reduced rate is caused by a reduction in the number of productive collisions rather than by a slow rate of penetration of the membrane-binding domain into the bilayer. PMID- 24233453 TI - Effects of metal ion binding on an oncomodulin mutant containing a novel calcium binding loop. AB - The Ca(2+)-binding protein oncomodulin was altered by cassette mutagenesis of the CD site (CDOM33) with a sequence that was derived by a consensus method using over 250 known Ca(2+)-binding loop sequences. This mutant was studied using time resolved and steady-state fluorescence from the Trp residue included at position 7 of the loop (position 57 of the protein sequence). The fluorescence characteristics of this species in the absence and presence of metal ions were compared to those of a tetradecapeptide containing the loop and the single Trp mutant of oncomodulin, Y57W. The fluorescence properties of CDOM33 were quite different from the peptide, both in the apo form and in response to metal binding. The consensus CD loop in CDOM33 exhibited the characteristics of a Ca(2+)/Mg(2+) site in contrast to the Ca(2+) specificity of the wild-type CD loop. The Trp analogue, 5-hydroxytryptophan (5HW), was incorporated into both oncomodulin mutants to produce Y75(5HW) and 5HW-CDOM33. Results showed that this intrinsic probe was relatively insensitive to structural changes in the mutants upon metal binding compared to Trp itself. PMID- 24233454 TI - Fluorescence studies and semiempirical calculations on alkali ion indicators. AB - Two newly synthesized cryptands act as sensitive Na(+)- and K(+)-selective indicators for cation concentrations above 20 MUM. The fluorescence properties change markedly upon cation binding. In addition, the free ligands exhibit a pronounced sensitivity to pH, which is considerably lower for the cation complexes. Time resolved fluorescence is characterized by a decay time of about 5 ns that is attributed to the diprotonated protolytic state of the uncomplexed ligands. Semiempirical calculations show the systematic influence of the nitrogen lone pairs or the N-H bond on the stability of the system. The cause of the strong fluorescence intensity increase observed upon protonation of the fluorescent cryptands may be attributed to an increase in the S1-T x energy gap as a consequence of bridgehead nitrogen protonation. PMID- 24233455 TI - lin-Benzo-ATP and-ADP: Versatile fluorescent probes for spectroscopic and biochemical studies. AB - lin-Benzo-adenine nucleotides can act not only as probes for fluorescence studies but also as structural active site probes for enzymes. To understand the basic properties oflin-benzo-ATP and-ADP, protolysis and Mg(2+) and Ca(2+), binding are investigated between pH 6.2 and pH 8.5 by spectrophotometric and spectrofluorometric titrations. Based on a reaction model, a set of equilibrium constants is determined which is consistent with all available experimental results. The pK values of the Mg(2+) and Ca(2+) complex oflin-benzo-ATP in the chosen medium are 4.6 and 4.1, respectively, and those for the corresponding diphosphate are 3.1 and 2.8, respectively. Fluorescence and absorption spectra are reported. PMID- 24233456 TI - Toward an understanding of the fluorescence intensity changes observed on fluorescein 5'-Isothiocyanate-Na(+),K (+)-ATPase. AB - The fluorescence emission intensity between the Na(+), and the K(+) complex of Na(+),K(+)-ATPase, labeled with fluorescein 5'-isothiocyanate (FITC), differs by 30 to 40%. Experimental studies are carried out to elucidate the physical reasons which account this intensity difference. The dissociation constant of protolysis of the covalently bound FITC and its fluorescence decay times are determined in media of different ionic compositions and are compared with the corresponding properties of a synthetic model compound. The fluorophore bound to the protein is characterized by two decay times in the nanosecond range; the model compound, by a single one. The static fluorescence intensity changes are discussed on the basis of these results. PMID- 24233457 TI - Triplet-state monitoring by fluorescence correlation spectroscopy. AB - The effects of high excitation intensities in fluorescence correlation spectroscopy (FCS) in terms of saturation and triplet-state build-up have been studied for the case of Rh6G in aqueous solution. It was found that FCS provides a powerful means for the determination of intersystem crossing and triplet-state depopulation rates of fluorophores in solution. PMID- 24233458 TI - Submillisecond detection of single rhodamine molecules in water. AB - Using a modified confocal fluorescence microscope and a CW argon laser, we have measured fluorescence bursts from diffusing single Rh6G molecules that clearly exceed the background intensity. The exact average number of molecules in the observable volume elements was measured directly via the fluorescence intensity autocorrelation function. This allowed us to estimate the probability of finding several molecules simultaneously in the volume element. A tradeoff between the number of detected fluorescence photons and the signal-to-background ratio was observed. In a volume element of 0.24 fl, 4 photoelectrons on average were detected from a molecule of Rh6G with a fluorescence-to-background ratio of 1000, while the volume element of 60 fl yielded on average 100 photoelectrons with a background of 25 counts. In fast single-molecule detection the intersystem crossing into the triplet state plays an important role, affecting the maximum emission rate from the molecule. PMID- 24233459 TI - dAbsolute Spectroscopic Determination of Cross-Membrane potential. PMID- 24233460 TI - [CdCl4]2- anion-induced coordination of alkaline earth metal ions to cucurbit[7]uril, corresponding supramolecular self-assemblies and potential application. AB - In the present work, we describe three cucurbit[7]uril-based coordination supermolecular self-assemblies in the presence of [M(trans)Cl4](2-). It can affect the construction of Q[7]/metal ions-based coordination polymers, at the same time it can result in the formation of Q[7]-based supramolecular assemblies when introducing the [M(trans)Cl4](2-) into the Q[7]/metal ions system. PMID- 24233461 TI - Indigenous sheep breeds of North Ethiopia: characterization of their phenotype and major production system. AB - A study was conducted in Tigrai, Northern Ethiopia to describe the sheep breeds and their production system. The survey was done in selected districts known for their high sheep population density. The phenotype characterization identified distinct features for each breed. The breeds are Aberegelle, Ille, Begait, and the common Tigrai highland sheep. The strong discriminating phenotypes are face profile, tail type, and compactness; accounting for 83.48, 17.95, and 2.93% respectively of the total variability among breeds. The flock structure are affected by the market demand; requirements of breeding females and feed availability. Farmers tend to keep more female sheep for longer (culling age of 5.9 +/- 0.4 and 1.9 +/- 0.5 for females and males, respectively) for the reasons of feed shortage and need to maximize number of breeding female. The ratio of male to overall female is large (1:6) and thus a single ram gets maximum contact time with ewes and ewe lambs. The overall average age at puberty for females is 9 14 months. However, the presence of very young lamb rams and uncontrolled mating system lead to early breeding of females which results in low conception rate, low birth weight, poor survival rates, and in extreme cases causing inbreeding. It was also possible to identify the critical control points such as breed, age of animals, nutrition, and feeding systems affecting the provision of live animals for good meat quality. PMID- 24233462 TI - Molecular detection of Cryptosporidium spp. infections in water buffaloes from northeast Thailand. AB - The objectives of this study were to determine the individual and herd-level prevalence and genotype of Cryptosporidium and to identify putative risk factors associated with Cryptosporidium spp. infections in water buffaloes in northeast Thailand. Fecal samples from 600 water buffaloes of 287 farms in six provinces were collected and tested using DMSO-modified acid-fast staining and polymerase chain reaction. The overall prevalence of Cryptosporidium infections in buffaloes was 5.7 and 8.7% among individual animals and herds, respectively. The provinces with highest infected Cryptosporidium were located in the Sakon Nakhon Basin in the northern part of the region. In addition, higher herd prevalence was observed among farms with more than five buffaloes (30%) than those with five or less animals (16.2%). Thirty (88.2%) of the 34 Cryptosporidium-positive samples were Cryptosporidium parvum and four (11.8%) were Cryptosporidium ryanae. PMID- 24233463 TI - The effect of sulfide on the blue-green algae of hot springs II. Yellowstone National Park. AB - In the Mammoth Springs (Yellowstone National Park) waters with near neutral pH and soluble sulfide (H2S, HS(-), S(2-)) of over 1-2 mg/liter (30-60MUM) are characterized by substrate covers of phototrophic bacteria (Chloroflexus and aChlorobium-like unicell) above 50?C and by a blue-green alga (Spirulina labyrinthiformis) below this temperature.Synechococcus. Mastigocladus, and other blue-green algae typical of most hot springs of western North America are excluded, apparently by sulfide. The sulfide-adaptedSpirulina photosynthesized at maximum rates at 45?C and at approximately 300 to 700MUEin/m(2)/sec of "visible" radiation. Sulfide (0.6-1.2 mM) severely poisoned photosynthesis of nonadapted populations, but those continuously exposed to over 30MUM tolerated at least 1 mM without inhibition. A normal(14)C-HCO3 photoincorporation rate was sustained with 0.6-1 mM sulfide in the presence of DCMU (7MUM) or NH2OH (0.2 mM), although both of these photosystem II inhibitors prevented photoincorporation without sulfide. Other sulfur-containing compounds (S2O3 (2-) SO3 (2-), S2O4 (2-) thioglycolic acid cysteine) were unable to relieve DCMU inhibition. The lowering of the photoincorporation rate by preferentially irradiating photosystem I was also relieved by sulfide. The most tenable explanation of these results is that sulfide is used as a photo-reductant of CO2, at least when photosystem II is inhibited. It is suggested that in some blue-green algae photosystem II is poisoned by a low sulfide concentration, thus making these algae sulfidedependent if they are to continue photosynthesizing in a sulfide environment. Presumably a sulfidecytochrome reductase enzyme system must be synthesized for sulfide to be used as a photo-reductant. PMID- 24233464 TI - Immunochemical investigation of four Saprolegnia species with parasitic activity in fish: Serological and kinetic characterization of a chymotrypsin-like activity. AB - The antigenic structure of four aquatic Phycomycetes of the genusSaprolegnia with parasitic activity in fish was analyzed with immunoelectrophoresis and double diffusion techniques. It is shown that these serological tests might represent a valuable criterion for the identification of the fourSaprolegnia species:S. parasitica, S. ferax, S. delica, andS. diclina. A specific chromogenic reaction revealed the presence of a protease with chymotrypsin-like activity among the precipitation arcs obtained after immunoelectrophoresis. Analysis of this proteolytic activity by kinetic assay methods confirmed the results of the serological tests. Moreover estimates of the quantity of enzyme present in the cellular extract and in the culture medium were obtained. A possible relationship between the proteolytic activity and the host-parasite interaction was discussed. PMID- 24233465 TI - Competition for inorganic substrates among chemoorganotrophic and chemolithotrophic bacteria. AB - In aerobic enrichment experiments with a chemostat, using phosphate-limited lactate medium, aSpirillum sp. predominated at the lower range of dilution rates. At the higher dilution rates an (chemoorganotrophic) unidentified rod-shaped bacterium came to the fore. The same result was obtained in competition experiments with pure cultures of the two bacteria. Growth parameters were: Rod,MU max=0.48 hr(-1),k s(PO4 (3-))=6.6*10(-N) M;Spirillum, MU max=0.24 hr(-1). ks(PO4 (3-)) =2.7*10(-8) M. TheSpirillum grew faster than the rod at low dilution rates, not only under phosphate-limitation but also in K(+)-,Mg(2+)-, NH4 (+)-, aspartate-, succinate-, and lactate-limited cultures. Both organisms showed little substrate specificity and could utilize a similar range of carbon and energy sources. The results support the view that part of the diversity among bacteria in the natural environment is based on selection toward substrate concentration. Another set of competition experiments was carried out with pure cultures of two marine obligately chemolithotrophic colorless sulfur bacteria,Thiobacillus thioparus andThiomicrospira pelophila. Tms. pelophila outgrewT. thioparus at low dilution rates under iron limitation, while the reverse was true at high dilution rates. It is concluded that the relatively fast growth ofTms. pelophila at low iron concentration may explain its higher sulfide tolerance. Organisms showing a selection advantage at very low concentrations of limiting substrates appear to have a relatively high surface to volume ratio. PMID- 24233466 TI - Transport equations for a microbial predator-prey community. AB - A transport equation is used which describes the temporal behavior of interacting populations in changing environments. The formulation takes into account the internal state variables of the individuals. The general theory is applied to the transient analysis of a microbial predator-prey system using an approximate model for the specific cell growth rate and multigroup formulism to approximate the mass distribution within the population. Experimental results in aTetrahymena pyriformis- Aerobacter aerogenes system have been used to evaluate the group parameters and test the validity of the theoretical predictions. PMID- 24233467 TI - The microbial ecology of the Great Salt Lake. AB - The Great Salt Lake is actually two lakes. A highly saline (330-gml(-1)) northern arm and a moderately saline (120-gml(-1)) southern arm separated by a semipermeable rock causeway. The lake, particularly the northern arm, has a massive accumulation of organic matter resulting from more than 100,000 years of productivity, cycling from a freshwater to a saline lake, plus the influence of human industry and agriculture in more recent times. The north arm planktonic and attached community consists principally of, in order of biomass: bacteria of at least two genera,Halobacterium andHalococcus; two algae,Dunaliella salina andD. viridis; the brine shrimp,Anemia salina; and, two species of brine fly,Ephydra gracilis andE. hians and possibly one more species. The algae and the bacteria appear to depend on each other for nutrients. The bacteria use organic matter produced by the algae and the algae use ammonia produced by the bacteria and possibly the brine shrimp. The production of ammonia appears to be the rate limiting step although there is no shortage of other forms of nitrogen in the north arm. Based on aquarium studies, the potential for biomass production of algae and bacteria is much higher than actually observed in the north arm, leading to the postulation of two additional factors controlling population; the grazing of the algae by invertebrates with the excretion of compounds rich in nitrogen, and the effect of a low habitat temperature and winter cold on the bacteria, reducing their metabolic activities to nearly zero. Some aspects of the various organisms and their metabolism are discussed. A comparison is made with recent work on the Dead Sea. PMID- 24233468 TI - Lysis ofEscherichia coli by a marine myxobacter. PMID- 24233470 TI - Gillingham: Contemporary after 76 years. PMID- 24233469 TI - The biology of APOL1 with insights into the association between APOL1 variants and chronic kidney disease. AB - Recent studies have identified genetic variants in APOL1 that may contribute to the increased incidence of kidney disease in populations with African ancestry. Here, we review the biology of APOL1 present in the circulation and localized to the kidney as it may contribute to the pathogenesis of APOL1-associated kidney disease. PMID- 24233471 TI - Defining dyslexia as a developmental language disorder. AB - Despite recent developments in research and theory, investigators and practitioners continue to rely on rather traditional definitions of dyslexia. This paper discusses some of the problems with traditional definitions and reviews a rapidly growing body of research that suggests a more comprehensive definition. According to this definition, dyslexia is a developmental language disorder that involves a deficit(s) in phonological processing. This disorder manifests itself in various phonological difficulties as well as a specific reading disability. PMID- 24233472 TI - Ordinary and extraordinary brain development: Anatomical variation in developmental dyslexia. AB - Eight brains, six male and two female, of reliably diagnosed cases of developmental dyslexia have been analyzed in this laboratory thus far. Common to all the specimens is the absence of ordinary asymmetry in the planum temporale, a language relevant area of the temporal lobe. In addition, the male cases and one female case displayed multiple focal areas of malformation of the cerebral cortex, located variably in the language relevant perisylvian regions and to a greater or lesser extent bilaterally. Both female cases and, to a mild degree, one of the males display focal areas of cortical scarring dated to the end of pregnancy through to the end of the second year of life at the latest. The scarring tends to be located in the vascular watershed territories.Experimental animal research suggests that symmetry may represent absence of the necessary developmental pruning of neural networks required for specific functions such as language. This diminished pruning results in excessive neurons and (at least interhemispheric) connections.Additional modeling in experimental animals suggests that cortical malformations and scarring similar to those seen in the dyslexic brains may represent early focal injury that could be attributed to congenital disorders of the immune system. PMID- 24233473 TI - Using genetics to understand dyslexia. AB - This paper reviews what is currently known about the genetics of dyslexia and shows how genetic studies can help clarify which symptoms are primary and which are secondary in dyslexia. On the genetic side, current evidence supports the view that dyslexia is familial, substantially heritable, and heterogeneous in its genetic mechanisms. At least some forms of familial dyslexia appear to be autosomal dominant, with linkage studies supporting both a major locus on chromosome 15 and genetic heterogeneity. On the symptom side, current evidence supports the view that the primary symptom in dyslexia is a deficit in the phonological coding of written language. This primary symptom likewise appears to be heritable. Recent evidence suggests that the heritable precursor to this written language deficit is a spoken language deficit in the skill of phoneme segmentation and awareness. PMID- 24233474 TI - Productive knowledge of derivational rules in poor readers. AB - The present report with two complementary experiments examined the productive knowledge of derivational morphology in 75 grade 4, 5, and 6 "poor" readers further divided into those performing better, or worse, inboth reading and spelling ((R + S +) or R - S -)), or better in the one or the other (mixed) subgroups. Experiment 1 required individual subjects to vocalize rapidly the derived forms of words when primed with 40 target base words in four derivational conditions or levels embedded in sentence frames shown on the computer screen. Experiment 2 required the reverse process of vocalizing the base forms of words when primed with 40, complex derived forms in the same four morphology conditions embedded in sentence frames shown on the computer screen. Results of the analysis of the reaction times show a developmental trend and that the subgroups of poor readers used different mechanisms in producing derived or base forms of words according to the complexity of the orthographic and/or phonological changes needed in the derivational process. The important role of morphemic structure and origin of words in instruction is emphasized. PMID- 24233475 TI - Effect of cues on object naming in first-grade good and poor readers. AB - Object-naming deficits in children with reading problems may be due to deficiencies in either the phonological stage of processing or the semantic stage. The present study approached this issue by manipulating the type of cue given (semantic or phonetic) when object drawings were not named correctly by first-grade children. Although the children who were poor readers named significantly fewer objects than the good readers, both groups of children benefited from phonetic cues. In contrast, semantic cues had relatively little effect. These results support the view that difficulty on object naming is more likely related to phonological deficiencies. PMID- 24233476 TI - Narratives: A window on the oral substrate of written language disabilities. AB - Oral precursors underlying competence with literacy activities are approached through a review of studies on narrative comprehension and production in children identified as language learning disabled (LLD). Areas addressed include a general overview of narrative types, the kinds of narrative knowledge that are acquired, the nature of story organization, and developmental acquisitions in story recall and generation. Nine studies on the oral comprehension and production of language learning disabled children are then compared with respect to methodological issues and patterns of performance. Implications from these studies are discussed in terms of their potential insight for subtypes of a LLD including the value of oral narratives in identifying precursors for competence with written language. PMID- 24233477 TI - Written narratives of normal and learning disabled children. AB - Writing samples of children in grades one through three were collected in two midwestern elementary schools using the Picture Story Language Test. Each story was scored for productivity, syntax, and level of abstraction. Results indicated that performance in all aspects of written language improved with age.A second study was conducted to compare the writing of normal children who were average readers in grades one through three with learning disabled children who were reading at comparable levels. The results indicated no significant differences in productivity but there were differences in syntax. Problems were noted particularly in morphology. Further observations indicated the learning disabled poor readers also had more problems with handwriting and spelling than average readers. PMID- 24233478 TI - Diagnosing comprehension deficits through listening and reading. AB - Assessment of students with reading comprehension difficulties should include measurement of both listening and reading comprehension of extended discourse in order to begin to identify the reason or reasons for their deficits. The problems of developing an effective comprehension test are discussed. An experimental screening test, Profiles in Listening and Reading (PILAR), is presented as one approach to assessing comprehension. Its potential as a screening and diagnostic test is considered, using students' profiles from two studies. PMID- 24233479 TI - Linguistic coding deficits in foreign language learners. AB - As increasing numbers of colleges and universities require a foreign language for graduation in at least one of their degree programs, reports of students with difficulties in learning a second language are multiplying. Until recently, little research has been conducted to identify the nature of this problem. Recent attempts by the authors have focused upon subtle but ongoing language difficulties in these individuals as the source of their struggle to learn a foreign language. The present paper attempts to expand upon this concept by outlining a theoretical framework based upon a linguistic coding model that hypothesizes deficits in the processing of phonological, syntactic, and/or semantic information. Traditional psychoeducational assessment batteries of standardized intelligence and achievement tests generally are not sensitive to these linguistic coding deficits unless closely analyzed or, more often, used in conjunction with a more comprehensive language assessment battery. Students who have been waived from a foreign language requirement and their proposed type(s) of linguistic coding deficits are profiled. Tentative conclusions about the nature of these foreign language learning deficits are presented along with specific suggestions for tests to be used in psychoeducational evaluations. PMID- 24233480 TI - Comparison of dyslexic and nondyslexic adults on decoding and phonemic awareness tasks. AB - This study was conducted to determine if the phonemic awareness skills of college aged dyslexic students (n=10) differ from those of their nondyslexic peers (n=10). Both groups were tested on reading of real and nonsense words and a phoneme reversal task. Although the dyslexic subjects had received considerable language remediation and were all succeeding at their college studies at a level that did not significantly differ from the nondyslexic subjects, they performed significantly poorer on two measures of phonemic awareness: reading of nonsense words and increased error rate and response time on reversal of common three phoneme words. These results were interpreted to suggest that although the dyslexic subjects had improved their reading skills there remained a fundamental deficit in their ability to process phonological information quickly and accurately. PMID- 24233481 TI - The relation between sense of audience and specific learning disabilities: An exploration. AB - The relationship between two college-able learning-disabled writers' unique social and cognitive profiles and the sense of audience in their written texts is explored. The first student demonstrated significant visual and organizational cognitive processing deficits. The second student had deficits in oral language comprehension and production. While the writing of both students was affected by their disabilities, our findings suggest that the quality of their audience awareness is indeed related to the nature of their specific learning disability profile. PMID- 24233482 TI - Prediction: A six-year follow-up. AB - The prereading and reading performance of a group of 370 predominantly Hispanic, bilingual public school children was followed for six years. The aim of the study was to compare the factorial make-up and predictive validity of tests used in the current research with findings from a previous study. The early study had followed the children from the end of their kindergarten year until the end of second grade. For purposes of the present study a 13-test predictor battery was administered to the children at the beginning of their first-grade year. This battery included a number of measures used in the early study, among them a 5 test Screening Index developed in the course of that study. Records were obtained of the follow-up children's 2nd, 3rd, 4th, 5th, and 6th grade reading test scores. Factor analysis of the pool of 13 predictor tests showed a two-cluster battery structure. These clusters closely resembled two of the four factors defined in the early study. As used with the group of bilingual children, the Screening Index misclassified many of the failing readers, as well as others who went ahead to read at grade level. The Screening Index quite accurately identified, across grades, children who eventually read well. A number of predictor tests administered at beginning of first grade continued to show significant correlations with reading at all grade levels. The consistent contribution of the predictor tests with reading points to their continuing usefulness as a point of departure for assessing children's readiness to read. PMID- 24233483 TI - Multisensory programs in the public schools: A brighter future for LD children. AB - A longitudinal study followed the progress of a group of elementary SLD students as they were instructed using the Alphabetic Phonics (AP) curriculum. After a three year period, the AP curriculum produced positive results in reading comprehension for most SLD students, particularly those who began the program in first and second grade. Students in resource and self-contained settings made significant gains in reading comprehension, although the two types of students exhibited different patterns of progress. Students of different ability levels responded differently to the AP curriculum. Average and above average students made significant progress in reading comprehension, but below average students did not advance substantially in relation to their ability level. At the end of three years, classroom teachers had a significantly more positive view of students' word attack, oral reading, and silent reading comprehension skills. PMID- 24233485 TI - Foreword. PMID- 24233484 TI - The adolescent dyslexic: Strategies for spelling. AB - The adolescent dyslexic student's problems with spelling are very different from those of a young dyslexic child, as he already has considerable knowledge of the English spelling system. But this knowledge is very often random and confused, so he needs to acquire a logical structure which will enable him to generate spelling for himself and to communicate effectively in writing.It will be suggested that accuracy is not always attainable, but the student can be taught to recognize and use the main components of the spelling system and can learn to employ all available resources. The general aim is to provide the dyslexic adolescent with the tools he needs to cope with his spelling requirements, both in school and outside; to make informed deductions; to think for himself. In short, to spell independently and logically. PMID- 24233486 TI - Translation of human tissue factor pathway inhibitor-beta mRNA is controlled by alternative splicing within the 5' untranslated region. AB - OBJECTIVE: Tissue factor pathway inhibitor (TFPI) blocks the initiation of coagulation by inhibiting TF-activated factor VII, activated factor X, and early prothrombinase. Humans produce two 3' splice variants, TFPIalpha and TFPIbeta, which are differentially expressed in endothelial cells and platelets and possess distinct structural features affecting their inhibitory function. TFPI also undergoes alternative splicing of exon 2 within its 5' untranslated region. The role of exon 2 splicing in translational regulation of human TFPI isoform expression is investigated. APPROACH AND RESULTS: Exon 2 splicing occurs in TFPIalpha and TFPIbeta transcripts. Human tissue mRNA analysis uncovered a wide variability of exon 2 expression. Polysome analysis revealed a repressive effect of exon 2 on TFPIbeta translation but not on TFPIalpha. Luciferase reporter assays further exposed strong translational repression of TFPIbeta (90%) but not TFPIalpha. Use of a Morpholino to remove exon 2 from TFPI mRNA increased cell surface expression of endogenous TFPIbeta. Exon 2 also repressed luciferase production (80% to 90%) when paired with the beta-actin 3' untranslated region, suggesting that it is a general translational negative element whose effects are overcome by the TFPIalpha 3' untranslated region. CONCLUSIONS: Exon 2 is a molecular switch that prevents translation of TFPIbeta. This is the first demonstration of a 5' untranslated region alternative splicing event that alters translation of isoforms produced via independent 3' splicing events within the same gene. Therefore, it represents a previously unrecognized mechanism for translational control of protein expression. Differential expression of exon 2 denotes a mechanism to provide temporal and tissue-specific regulation of TFPIbeta-mediated anticoagulant activity. PMID- 24233487 TI - New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis. AB - OBJECTIVE: Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy. APPROACH AND RESULTS: sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41; P=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75; P=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37; P=0.012). Nuclear magnetic resonance-derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals. CONCLUSIONS: This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals. PMID- 24233488 TI - Acid sphingomyelinase regulates platelet cell membrane scrambling, secretion, and thrombus formation. AB - OBJECTIVE: Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation. APPROACH AND RESULTS: Collagen-related peptide induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (Smpd1(-/-)) when compared with platelets from wild-type mice (Smpd1(+/+)). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in Smpd1(-/-) platelets than in Smpd1(+/+) platelets. In contrast, platelet integrin alphaIIbbeta3 activation and aggregation, as well as activation dependent Ca(2+) flux, were not significantly different between Smpd1(-/-) and Smpd1(+/+) platelets. In vitro thrombus formation at shear rates of 1700 s(-1) and in vivo thrombus formation after FeCl3 injury were significantly blunted in Smpd1(-/-) mice while bleeding time was unaffected. Asm-deficient platelets showed significantly reduced activation-dependent ceramide formation, whereas exogenous ceramide rescued diminished platelet secretion and thrombus formation caused by Asm deficiency. Treatment of Smpd1(+/+) platelets with bacterial sphingomyelinase (0.01 U/mL) increased, whereas treatment with functional acid sphingomyelinase-inhibitors, amitriptyline or fluoxetine (5 MUmol/L), blunted activation-dependent platelet degranulation, phosphatidylserine exposure, and thrombus formation. Impaired degranulation and thrombus formation of Smpd1(-/-) platelets were again overcome by exogenous bacterial sphingomyelinase. CONCLUSIONS: Acid sphingomyelinase is a completely novel element in the regulation of platelet plasma membrane properties, secretion, and thrombus formation. PMID- 24233489 TI - Inflammatory stress induces statin resistance by disrupting 3-hydroxy-3 methylglutaryl-CoA reductase feedback regulation. AB - OBJECTIVE: The risk of cardiovascular disease is increased by up to 33 to 50* in chronic inflammatory states and convention doses of statins may not provide the same cardiovascular protection as in noninflamed patients. This study investigated whether the increase in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-R)-mediated cholesterol synthesis observed under inflammatory stress was resistant to the action of statins and if so, whether this was because of interference with the sterol regulatory element binding protein cleavage activating protein pathway. APPROACH AND RESULTS: Inflammatory stress was induced by adding cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6) and lipopolysaccharides to vascular smooth muscle cells in vitro and by subcutaneous casein injection in apolipoprotein E/scavenger receptors class A/CD36 triple knockout mice in vivo. Inflammatory stress exacerbated cholesterol ester accumulation and was accompanied in vitro and in vivo by increased HMGCoA-R mRNA and protein expression mediated via activation of the sterol regulatory element binding protein cleavage-activating protein/sterol regulatory element binding protein-2 pathway. Atorvastatin reduced HMGCoA-R enzymatic activity and intracellular cholesterol synthesis in vitro. However, inflammatory stress weakened these suppressive effects. Atorvastatin at concentrations of 16 MUmol/L inhibited HMGCoA-R activity by 50% in vascular smooth muscle cells, but the same concentration resulted in only 30% of HMGCoA-R activity in vascular smooth muscle cells in the presence of interleukin-1beta. Knocking down sterol regulatory element binding protein cleavage-activating protein prevented statin resistance induced by interleukin-1beta, and overexpression of sterol regulatory element binding protein cleavage-activating protein induced statin resistance even without inflammatory stress. In vivo, the amount of atorvastatin required to lower serum cholesterol and decrease aortic lipid accumulation rose from 2 to 10 mg/kg per day in the presence of inflammatory stress. CONCLUSIONS: Increased cholesterol synthesis mediated by HMGCoA-R under inflammatory stress may be one of the mechanisms for intracellular lipid accumulation and statin resistance. PMID- 24233493 TI - Aesthetic shoulder augmentation with silicone implants. AB - BACKGROUND: Men with narrower shoulders may appear less muscular than other men. Deltoid muscle underdevelopment or atrophy, a condition commonly linked to narrow shoulder issues, may be associated with congenital deformity, trauma, or neoplasm. For some people, regular exercise does not effectively develop the deltoid muscle region. Some people naturally have a smaller build than others. Even with developed deltoid muscles, these people still appear to be small. The authors have performed lateral shoulder augmentation with silicone implants for 4 years. Based on their experience, this procedure stands as a reliable solution for men with narrow shoulders. METHODS: Lateral shoulder augmentation with silicone implants was developed and used for 81 patients between April 2009 and April 2013. None of the patients had shoulder deformities except for two patients (one patient with Poland's syndrome and one patient with Sprengel's deformity). The implants were placed through a horizontal axillary crease incision in a plane dissected between the deltoid fascia and muscle. RESULTS: All augmentation or correction procedures have been met with complete patient approval. Five patients had minor complications such as hematoma and implement displacement. However, all these complications were resolved to the satisfaction of the patients. CONCLUSION: When silicone implants are used to achieve purely aesthetic improvements, successful shoulder augmentation procedures are observed. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 . PMID- 24233492 TI - Deficiency of NOX1/nicotinamide adenine dinucleotide phosphate, reduced form oxidase leads to pulmonary vascular remodeling. AB - OBJECTIVE: Involvement of reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase has been documented in the development of hypoxia-induced model of pulmonary arterial hypertension (PAH). Because the PAH-like phenotype was demonstrated in mice deficient in Nox1 gene (Nox1(-/Y)) raised under normoxia, the aim of this study was to clarify how the lack of NOX1/NADPH oxidase could lead to pulmonary pathology. APPROACH AND RESULTS: Spontaneous enlargement and hypertrophy of the right ventricle, accompanied by hypertrophy of pulmonary vessels, were demonstrated in Nox1(-/Y) 9 to 18 weeks old. Because an increased number of alpha-smooth muscle actin positive vessels were observed in Nox1(-/Y), pulmonary arterial smooth muscle cells (PASMCs) were isolated and characterized by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In Nox1(-/Y) PASMCs, the number of apoptotic cells was significantly reduced without any change in the expression of endothelin-1, and hypoxia-inducible factors HIF 1alpha and HIF-2alpha, factors implicated in the pathogenesis of PAH. A significant decrease in a voltage-dependent K(+) channel, Kv1.5 protein, and an increase in intracellular potassium levels were demonstrated in Nox1(-/Y) PASMCs. When a rescue study was performed in Nox1(-/Y) crossed with transgenic mice overexpressing rat Nox1 gene, impaired apoptosis and the level of Kv1.5 protein in PASMCs were almost completely recovered in Nox1(-/Y) harboring the Nox1 transgene. CONCLUSIONS: These findings suggest a critical role for NOX1 in cellular apoptosis by regulating Kv1.5 and intracellular potassium levels. Because dysfunction of Kv1.5 is among the features demonstrated in PAH, inactivation of NOX1/NADPH oxidase may be a causative factor for pulmonary vascular remodeling associated with PAH. PMID- 24233490 TI - Protein S is a cofactor for platelet and endothelial tissue factor pathway inhibitor-alpha but not for cell surface-associated tissue factor pathway inhibitor. AB - OBJECTIVE: Tissue factor pathway inhibitor (TFPI) is produced in 2 isoforms: TFPIalpha, a soluble protein in plasma, platelets, and endothelial cells, and TFPIbeta, a glycosylphosphatidylinositol-anchored protein on endothelium. Protein S (PS) functions as a cofactor for TFPIalpha, enhancing the inhibition of factor Xa. However, PS does not alter the inhibition of prothrombinase by TFPIalpha, and PS interactions with TFPIbeta are undescribed. Thus, the physiological role and scope of the PS-TFPI system remain unclear. APPROACH AND RESULTS: Here, the cofactor activity of PS toward platelet and endothelial TFPIalpha and endothelial TFPIbeta was quantified. PS enhanced the inhibition of factor Xa by TFPIalpha from platelets and endothelial cells and stabilized the TFPIalpha/factor Xa inhibitory complex, delaying thrombin generation by prothrombinase. By contrast, PS did not enhance the inhibitory activity of TFPIbeta or a membrane-anchored form of TFPI containing the PS-binding third Kunitz domain (K1K2K3) although PS did function as a cofactor for K1K2K3 enzymatically released from the cell surface. CONCLUSIONS: The PS-TFPI anticoagulant system is limited to plasma TFPIalpha and TFPIalpha released from platelets and endothelial cells. PS likely functions to localize solution-phase TFPIalpha to the cell surface, where factor Xa is bound. PS does not alter the activity of membrane-associated TFPI. Because activated platelets release TFPIalpha and PS, the PS-TFPIalpha anticoagulant system may act physiologically to dampen thrombin generation at the platelet surface. PMID- 24233491 TI - Cyclic adenosine monophosphate-response element-binding protein mediates the proangiogenic or proinflammatory activity of gremlin. AB - OBJECTIVE: Angiogenesis and inflammation are closely related processes. Gremlin is a novel noncanonical vascular endothelial growth factor receptor-2 (VEGFR2) ligand that induces a proangiogenic response in endothelial cells (ECs). Here, we investigated the role of the cyclic adenosine monophosphate-response element (CRE)-binding protein (CREB) in mediating the proinflammatory and proangiogenic responses of ECs to gremlin. APPROACH AND RESULTS: Gremlin induces a proinflammatory response in ECs, leading to reactive oxygen species and cyclic adenosine monophosphate production and the upregulation of proinflammatory molecules involved in leukocyte extravasation, including chemokine (C-C motif) ligand-2 (Ccl2) and Ccl7, chemokine (C-X-C motif) ligand-1 (Cxcl1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Accordingly, gremlin induces the VEGFR2-dependent phosphorylation, nuclear translocation, and transactivating activity of CREB in ECs. CREB activation mediates the early phases of the angiogenic response to gremlin, including stimulation of EC motility and permeability, and leads to monocyte/macrophage adhesion to ECs and their extravasation. All these effects are inhibited by EC transfection with a dominant-negative CREB mutant or with a CREB-binding protein CREB interaction inhibitor that competes for CREB/CRE binding. Also, both recombinant gremlin and gremlin-expressing tumor cells induce proinflammatory/proangiogenic responses in vivo that are suppressed by the anti inflammatory drug hydrocortisone. Similar effects were induced by the canonical VEGFR2 ligand VEGF-A165. CONCLUSIONS: Together, the results underline the tight cross-talk between angiogenesis and inflammation and demonstrate a crucial role of CREB activation in the modulation of the VEGFR2-mediated proinflammatory/proangiogenic response of ECs to gremlin. PMID- 24233494 TI - Clover-shaped advancement flap for correction of short and broad columella in a patient with frontorhiny. AB - This report describes a recessively inherited frontonasal malformation termed "frontorhiny" in recent literature. The authors developed a modified open rhinoplasty incision for correction of a broad, swollen columella due to frontorhiny. The clover-shaped flap was composed of a central V-Y advancement flap and bilateral folding flaps. This report relates the case of an 8-year-old girl with a broad columella and poor nasal tip development treated by a clover shaped flap with dorsal onlay augmentation using autologous rib cartilage. This clover-shaped flap technique may be useful not only in frontorhiny cases but also in other cases of a short and broad columella. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 24233495 TI - Statistical methods to apportion the sources of particles in the industrial region of Estarreja-Portugal. AB - Factor analysis models are very attractive for source apportionment and have been widely applied. They do not require a priori knowledge of the number and composition of the sources, and they can actually uncover previously unsuspected sources and estimate the composition of the sources using only ambient monitoring data.Aerosol particles were collected from an industrial atmosphere and analyses for water soluble and carbon components. Principal components analysis permitted the evaluation of the contribution due to industries, soil fraction, secondary pollutants and sea spray particles of the total suspended aerosol mass.It can be concluded that the atmospheric aerosol in the Industrial Area of Estarreja (Portugal) contains a relative important fraction that is water soluble. Ammonium sulphates and nitrates are the main components of this fraction. Carbon compounds constitute about 30% of the total aerosol mass. These compounds are mainly formed by organic matter emitted by the industries. Due to the mutagenic and carcinogenic characteristics of some organic compounds processed in the Industrial Area (vinyl chloride, benzene, aniline, etc.), the concern exists of negative human health effects as a result of prolonged inhalation. Soil compounds is another important fraction of the aerosol mass, mainly in summer with dry, sunny and windy weather conditions.A more conclusive idea of the sources and effects of aerosol matter can only be obtained with the specific analysis of organic compounds and the determination of trace elements, characteristic of each particular source. PMID- 24233496 TI - The distribution of monthly rainfall intensity at some sites in Saudi Arabia. AB - The analysis of rainfall intensity is useful in various fields of life e.g. agricultural planning, hydrology and transmission of microwaves and high-voltage electricity. The monthly precipitation totals for a 21 year period are used to compare the rainfall regimes at seven sites in Saudi Arabia. These sites differ in their latitude, longitude and elevation above sea level. Some basic monthly statistics of data from these sites are presented to identify the nature of the rainfall at each site. The trend of the number of dry months per year is also used to compare between the sites. The probability of dry months for each month of the 21 yr is used for comparison between the rainfall regimes. Plots for mean and maximum rainfall at these sites are presented. The Fisher-Cornish proposed model for rainfall in arid regions is considered and a simple empirical method for estimating its parameters is used for the twelve month period rainfall data from the seven sites. PMID- 24233497 TI - The economics of transboundary air pollution in Europe. AB - Acid rain is causing substantial damage in all Eastern and Western European countries. This article presents a stepwise linear optimisation model, that places transboundary air pollution by SO2 and NOx in a game theoretical framework. The national authorities of 28 countries are perceived as players in a game in which they can choose optimal strategies. It is illustrated that optimal national abatement programmes may be far from optimal if considered from an international point of view. Several scenarios are discussed, including a reference case, full cooperation, Pareto optimality and a critical loads approach. The need for international cooperation and regional differentiation of abatement programmes is emphasised. PMID- 24233498 TI - True and false positive rates in maximum contaminant level tests. AB - The U.S. Environment Protection Agency (EPA) is promulgating a revised national primary drinking water regulation (NPDWR) which includes a monthly sample size and maximum contaminant level (MCL) for total coliform bacteria in public water systems. No previous quantification has been made of the coliform content that must be present in the sampled water in order for an MCL to be exceeded. This paper presents a method for evaluating the coliform level an MCL will detect with likelihood P.Our approach is to treat an MCL as a decision rule, with Type I (false positive) and Type II (false negative) error rates. The stringency of an MCL is quantified as the mean coliform level in the sampled system that it will detect with likelihood P. MCLs are contrasted on stringency by comparing the mean coliform level each targets for detection, with fixed error rates.Interim rules (NIPDWR), in effect since 1975, are shown to vary widely on the coliform content each targets for detection, that is, on stringency. Yes/no decisions on contamination have not been decided based on mean coliform content. Coliform levels permitted in monitored public water systems have been determined by the particular MCL used for testing. The same coliform level will test positively with one MCL 90 times in 100 yet be guaranteed 95% nondetection by a second MCL.EPA's reasonably safe standard for drinking water is reformulated on our stringency criteria. Its proposed monthly MCL is evaluated on its capability for maintaining this standard. Smaller systems will not provide its users this level of protection under the new rule.In addition, our evaluation of the safe water standard on stringency and the rationale for a monthly MCL require that coliform levels be identically distributed (i.d.) across month and sampled system. Empirical data strongly refute this model and question the utility of a monthly MCL.This work suggests an alternative, single sample MCL, with repeat sampling for verification, which can be configured to provide monitoring to discover mean coliform values at any level, in any size of system, at minimal extra cost. PMID- 24233499 TI - Statistical analysis of effects of measures against agricultural pollution. AB - The Norwegian Government has initiated a plan to reduce agricultural pollution. One of the projects in this plan is aimed at investigating the effects of different measures in order to evaluate their effects and costs.A set of experiments has been designed to estimate the effects of measures to reduce or control the use of fertilizers and erosion. The project started in 1985. It comprises continuous measurements in two water courses in each of four counties: one test drainage area where the relevant measures were implemented at the end of 1986, and one reference area where no specific measures are carried out. A series of chemical parameters are measured together with runoff and other hydrological and meteorogical data.The paper provides a preliminary analysis of the data collected in one of the counties during the period June 1985 to April 1988. It contains examples of analysis of covariance to show possible effects of the measures carried out in the test area.Natural variations in precipitation and pollution are large, making it difficult to see the effects of the measures without using statistical techniques to take the multivariability of the problem into account. Some effects can be shown with analysis of covariance. However, the relatively short measurement period makes it neccessary to be careful when interpreting the results. PMID- 24233500 TI - Air pollution and diseases of the respiratory tracts in pre-school children: A transfer function model. AB - The purpose of the present statistical analysis was the assessment of the relation between time series of environmental factors and of frequencies of diseases of the respiratory system in pre-school children. During about one year, daily measurements of air pollutants and climatic variables were taken. During the same period of time two series of medical data were collected: (i) The daily relative number of pre-school children, exhibiting diseases of the respiratory tracts who either came to the outpatients' clinic of the children's hospital or were reported by paediatricians in Basle (ENTRIES). (ii) The daily relative frequency of symptoms of the respiratory tracts observed in a group of randomly selected pre-school children (SYMPTOMS).By means of transfer function models the relation between the two target variables and the 'explaining' variables was analysed. Several practical problems did arise: Choice of the appropriate transformation of the different series, interpretation of the crosscorrelation function using different methods of 'prewhitening', time splitting and nonstationarity of the crosscorrelation structure. In particular, it was found that after prewhitening the crosscorrelation function between the explanatory series SO2 and the response series SYMPTOMS changes with time. While during the 'winter period' an instantaneous relation between these two series (and to a lesser extent between NO2 and SYMPTOMS) was identified, no such relation was found for the other seasons. PMID- 24233501 TI - The Niagara River: A water quality management overview. AB - The Niagara River constitutes part of the Laurentian Great Lakes and St. Lawrence River system which represents approximately 80% of North America's supply of surface fresh water. The river is a major source of water for industry, municipalities, recreation and power generation and is the link between Lakes Erie and Ontario. The river forms part of the Canada-U.S. border and falls under the jurisdiction of both countries.The massive industrialization of the region surrounding the river has led to a typical resource use conflict situation in which pollution of the river continues to be a major public concern.A number of constitutional, institutional and jurisdictional factors make the management of the Niagara River an involved and complicated matter. The interests, intent, philosophies, laws and regulations are not necessarily the same among the numerous jurisdiction involved. Despite these differences, however, Canada and the United States have succeeded in developing and implementing a model cooperative international management plan for the river. An overview of the main international aspects relating to the development and implementation of this plan, the Niagara River Toxics Management Plan, is presented. PMID- 24233502 TI - Time series valued experimental designs: A review. AB - A review is given of the literature on time-series valued experimental designs. Most of this literature is divided into two categories depending upon the factor status of the time variable. In one category, time is an experimental factor, and in the other it is a non-specific factor and enters the design in the context of replications. Analyses in both the time and frequency domain are reviewed. Signal detection models, Bayesian methods and optimal designs are surveyed. A discussion is also presented of application areas which include field trials and medical experiments. A main theme of the literature is that application of standard F tests to highly correlated data can be misleading. A bibliography of relevant publications from 1949 onward is presented. PMID- 24233503 TI - Extent of acidification in Southwestern Quebec lakes. AB - This paper presents the results from the first two areas covered by the statistically-oriented Quebec Spatial Lake Acidity Monitoring Network (RESSALQ). It is used in combination with the existing LRTAP-Quebec temporal network, the Quebec precipitation sampling network (REPQ) and a dose-effect model (SIGMA/SLAM) in order to assess the global extent of damages related to acidity, to detect changes in water quality, and to measure the effects of wet sulphate deposition reduction and those of sulphate target loadings on lake acidity. Results obtained with this network were also used in combination with data issued from the Eastern Lake Survey, in order to establish the relative acidity and sensitivity status of lakes in Eastern North America. While Florida has the highest proportion of very acidic and very sensitive lakes, Quebec has a higher overall proportion of sensitive and acidic lakes compared to other areas of the United States. PMID- 24233504 TI - A statistical approach to field measurements of the chemical evolution of cold (<0 degrees C) snow cover. AB - Two statistical methods for the analysis of data on the evolution of the chemical composition of cold snow (<0 degrees C) in the field (Lac Laflamme, Quebec) were compared. The methods used on the data were regression analysis (One sample per sampling date over a long cold period) and ANOVA (replicate samples on a restricted number of sampling dates over shorter periods). The relative power of the tests to determine the detectable amplitude of chemical changes was derived from the theoretical power of the tests under comparable conditions of sampling (number of observations) and from the estimated error variances of the measured data.The results of the study on the evolution of sulfates (SO4) concentrations in discretely identified snow strate clearly showed that for six of the eight strata, significant losses of SO4 occurred in snow during cold periods. The relative amplitude of the significant losses varied between 1% per day and 4% per day depending on the initial concentrations in the snow and the prevailing meteorological conditions.The analysis of the data also demonstrated that for the same number of samples, the regression analysis is more efficient in detecting the chemical changes in snow than the alternative ANOVA method. The use of this information to plan sampling programs of cold snow under both field and laboratory conditions is discussed. PMID- 24233505 TI - Statistical control of hygienic quality of bathing water. AB - In Denmark the hygienic quality of the bathing water has been controlled, based on general guidelines since 1978. Today more than 1100 control sites in marine areas have been established to ensure safe bathing water quality. According to EEC directives and Danish tradition, the control is usually performed by measuring the content of the indicator bacteria Escherichia coli (E. coli) in 5 to 20 test samples each bathing season.In Denmark, control programmes and data are evaluated using basic statistical quality control principles. This paper presents general guidelines for bacterial control, their statistical background and practical application. Furthermore, the evaluation and application of a specific programme for control of Staphylococcus aureus (S. aureus) are presented. This programme was used in a Danish bay where the authorities prescribe direct control of these potentially harmful bacteria. PMID- 24233506 TI - Relationships between water mass characteristics and estimates of fish population abundance from trawl surveys. AB - The Canadian Department of Fisheries and Oceans conducts annual bottom trawl surveys to monitor changes in the abundance of the major commercially important groundfish populations. Some of these surveys have been in operation for almost 20 yr. The estimates from these surveys often indicate rapid changes in abundance over time beyond that expected from the population dynamics of the fish. Much of this interannual change has been interpreted as variation, the magnitude of which has often made it difficult to measure anything but the most severe effects of fishing, pollution or any other intervention on the population. Recent studies have shown that some of this variation may be attributed to changes in catchability of fish due to the effects of environmental variables on fish distribution. Annual changes in abundance as estimated from such field surveys may be confounded by changes in catchability due to annual changes in environmental conditions. In this study, trawl catches of age 4 Atlantic cod (Gadus morhua) from surveys conducted during March 1979-1988 were compared with concurrent measurements of bottom salinity, temperature and depth. Large catches of age 4 cod are more likely to occur in water characterized as the intermediate cold layer defined by salinities of 32-33.5 and temperatures<5 degrees C. This relationship also appears to be modified by depth. We further show that internnual changes in the estimated abundance from the surveys were, in a number of cases, coincident with changes in the proportion of the bottom water composed of the intermediate cold water layer. The implications that these patterns may have on interpreting trends in the estimates of abundance from trawl surveys are discussed. PMID- 24233507 TI - Sampling inference, an alternate statistical model. AB - Sampling inference is proposed as an alternate paradigm. This method is discussed with respect to classical, Bayesian and a proposed probabilistic real world system. A probabilistic real world system is suggested as more valid and useful in practical as well as research situations. Sampling inference applied to a probabilistic model allows for valid inferences for volunteer and representative as well as random samples. A concept of time and distance based samples is introduced. PMID- 24233508 TI - Statistical needs in national water quality monitoring programs. AB - The concept that a few well chosen, strategically placed, water quality stations can provide valuable scientific information to water managers is common to many countries. Historically within Canada, water quality regional networks (Great Lakes network, Prairie Provinces Water Board network, Long Range Transport of Airborne Pollutants network, etc.) have been successfully operating for many years. This paper will describe the difficulties associated with developing a national water quality network for a country the size of Canada. In particular, it will describe some of the statistical tools presently being used in regional networks which are suitable for a national network, and discuss the need to develop new statistical tools for environmental monitoring in the 1990's. PMID- 24233509 TI - An application of multivariate analysis to acid rain data in Northern Italy to discriminate natural and man-made compounds. AB - This paper presents the preliminary results of a study, the aim of which was to analyse the pluviometric and chemical rain data, recorded by a wet only network located in Northern Italy.More in detail, precipitations were collected on a weekly basis and chemical analysis was performed on pH, electric conductivity and Ca, Mg, Na, K, NH4, NO3, SO4, Cl concentrations.The Principal Components Analysis pointed out that the first three components are enough to explain more than 90% of the variability of the parameters. Moreover each component may have a different physical interpretation, that is the first one is mainly related to the precipitation amount, while the second to the man made and natural sources and the last one to the sea/soil contribution. PMID- 24233510 TI - Characterization of hydrocarbon contaminated areas by multivariate statistical analysis: Case studies. AB - Analysis of soil gases is a relatively rapid and inexpensive method to delineate and measure hydrocarbon contamination in the subsurface caused by diesel or gasoline. Techniques originally developed for petroleum exploration have been adapted to tracking hydrocarbons which have leaked or spilled at or below the earth's surface.Discriminant analysis (a multivariate statistical technique) is used to classify soil gas samples of C1 to C7 hydrocarbons as biogenic (natural soil gases) or thermogenic (contaminant hydrocarbons). Map plots of C1 to C7 total interstitial hydrocarbons, C2 to C7 interstitial hydrocarbons, and C1/SigmaC n rations are used to further delineate and document the extent and migration of contamination.Three case studies of the technique are presented: each involves leakage of hydrocarbons from underground storage tanks. Soil gas analysis clearly defines the spread of contamination and can serve as the basis for the correct placement of monitoring wells. The method proved to be accurate, rapid, and cost-effective; it therefore has potential for widespread application to the identification of soil and groundwater contaminated by hydrocarbons. PMID- 24233511 TI - Framework for enhancing the statistical design of aquatic environmental studies. AB - Aquatic environmental studies can be categorized by the breadth of their scope and the types of desired results. The use of this categorization coupled with a clear specification of objectives and a judicious knowledge of the environmental variability should lead to more statistically efficient studies. This paper discusses the types of lacustrine studies commonly encountered in terms of their categorization. It provides examples of how the intrinsic environmental variability can influence their design and stresses the importance of properly stated objectives, the developing of testable hypotheses, the design of robust and powerful studies, and the importance of evaluating the implication of changes as critical factors for conducting effective and efficient environmental studies. PMID- 24233512 TI - Analysis of two-way layout of count data with negative binomial variation. AB - A number of methods has been proposed for dealing with single-factor or factorial experiments when the requirements for performing the normal theory analysis of variance procedure are not satisfied. This paper suggests the use of the likelihood ratio statistic for testing the main effects and the interaction between the factors in two-way layout of count data following negative binomial distributions with a common dispersion parameter. The likelihood ratio statistic for testing the equality of the dispersion parameters of several groups of count data is also derived. The methods is illustrated by an example concerning the study of spatial and temporal variation of bacterial counts. PMID- 24233513 TI - An overview of the acidification of lakes in Atlantic Canada. AB - Analysis of water chemistry from a sample of lakes (?1300) in Atlantic Canada has indicated that lakes in geologically sensitive portions of Nova Scotia and Newfoundland have been acidified due to the combined effects of natural organic acids and anthropogenically derived mineral acids. Principal component analysis of six measured variables (pH, Ca, Conductance, SO inf4 (sup*) , Alkalinity, Colour) and one computed variable (Alk/Ca(*)+Mg(*)) for each province result in four components which retain at least 89% of the original variability. Cluster analysis of the four principal components resulted in 6 lake groups for New Brunswick and 8 groups for Nova Scotia and 7 groups for Newfoundland. Geographic ordination of these clusters indicates that there is good correspondence between cluster group and the underlying bedrock geology of the region. PMID- 24233514 TI - Statistical inference from multiply censored environmental data. AB - Maximum likelihood estimation for multiply censored samples are discussed. Approximate confidence intervals for the lognormal mean are obtained using both Taylor expansion method and direct method. It is shown that the direct method performs noticeably better than the Taylor expansion method. Simulation results and applications are provided. PMID- 24233515 TI - Editorial. PMID- 24233518 TI - More than two HANDs to tango. AB - Developing a validated tool for the rapid and efficient assessment of cognitive functioning in HIV-infected patients in a typical outpatient clinical setting has been an unmet goal of HIV research since the recognition of the syndrome of HIV associated dementia (HAD) nearly 20 years ago. In this issue of JNIP Cross et al. report the application of the International HIV Dementia Scale (IHDS) in a U.S. based urban outpatient clinic to evaluate its utility as a substitute for the more time- and effort-demanding formalized testing criteria known as the Frascati criteria that was developed in 2007 to define the syndrome of HIV-associated neurocognitive disorders (HAND). In this study an unselected cohort of 507 individuals (68 % African American) that were assessed using the IHDS in a cross sectional study revealed a 41 % prevalence of cognitive impairment (labeled 'symptomatic HAND') that was associated with African American race, older age, unemployment, education level, and depression. While the associations between cognitive impairment and older age, education, unemployment status and depression in HIV-infected patients are not surprising, the association with African American ancestry and cognitive impairment in the setting of HIV infection is a novel finding of this study. This commentary discusses several important issues raised by the study, including the pitfalls of assessing cognitive functioning with rapid screening tools, cognitive testing criteria, normative testing control groups, accounting for HAND co-morbidity factors, considerations for clinical trials assessing HAND, and selective population vulnerability to HAND. PMID- 24233520 TI - MAPK kinase 3 is a tumor suppressor with reduced copy number in breast cancer. AB - Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here, we show that the mitogen-activated protein kinase (MAPK) MKK3 suppresses the growth of breast cancer, in which it varies in copy number. A pervasive loss of MKK3 gene copy number in patients with breast cancer is associated with an impairment of MKK3 expression and protein level in malignant tissues. To assess the functional role of MKK3 in breast cancer, we showed in an animal model that MKK3 activity is required for suppression of tumor growth. Active MKK3 enhanced expression of the cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1), leading to increased cell-cycle arrest in G1 phase of the cell cycle. Our results reveal the functional significance of MKK3 as a tumor suppressor and improve understanding of the dynamic role of the MAPK pathway in tumor progression. PMID- 24233519 TI - The novel tetramethylpyrazine bis-nitrone (TN-2) protects against MPTP/MPP+ induced neurotoxicity via inhibition of mitochondrial-dependent apoptosis. AB - Mitochondrial-dependent apoptosis plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Methyl-4-phenyl-1,2,3,6-tetra- hydropyridine (MPTP), the most widely used neurotoxin to simulate PD, is converted to 1-methyl-4-phenylpyridinium (MPP(+)) in vivo. MPP(+) induces excessive intracellular reactive oxygen species (ROS), leading to mitochondrial dependent apoptosis via sequentially opening mitochondria permeability transition pore (mPTP) to release cytochrome c from mitochondria into cytoplasm and activate pro-apoptotic caspase proteins. We have previously synthesized 2,5-[[(1,1 dimethylethyl)oxidoimino]methyl]-3,6-trimethylpyrazine (TN-2), a novel derivative of the Chinese herb medicine tetramethylpyrazine (TMP). TN-2 is armed with two powerful free radical-scavenging nitrone moieties. TN-2 significantly reversed the loss of dopaminergic neurons in the substantia nigra and the decrease in dopamine level in the striatum induced by MPTP in mice. TN-2 ameliorated the MPTP induced decrease of brain superoxide dismutase activity and glutathione concentration and increase of brain malondialdehyde. In addition, TN-2 inhibited MPP(+)-induced neuronal damage/apoptosis in primary cerebellum granular neurons (CGNs) and SH-SY5Y cells. TN-2 decreased excessive intracellular ROS, prevented the loss of mitochondrial membrane potential, blocked the release of mitochondrial cytochrome c and inhibited the activation of caspase-3 and caspase 9. Moreover, TN-2 treatment increased the mRNA expression of mitochondrial biogenesis factors peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PGC- 1alpha and beta) and mitochondrial transcription factor A (Tfam) in SH-SY5Y cells and CGNs. These results suggest that TN-2 protects dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity via the inhibition of mitochondrial-dependent apoptosis and possibly via the activation of mitochondrial biogenesis, indicating that TN-2 is a potential new treatment for PD. PMID- 24233521 TI - Transient expression of chloramphenicol acetyltransferase (CAT) gene in barley cell cultures and immature embryos through microprojectile bombardment. AB - Transient expression of chloramphenicol acetyl transferase gene has been detected in cultured barley (Hordeum vulgare L. cv. Heartland) cells and freshly isolated immature zygotic embryos (cv. Ellice) following the introduction of the gene by microprojectile bombardment. The DNA expression vector used to introduce the CAT gene, pCaMVI1CN, is a pUC8 derivative and consisted of a CaMV35S promoter, a fragment of alcohol dehydrogenase intron1, a CAT coding region and NOS polyadenylation region. The inclusion of the Adh1 intron1 was essential for the expression of CAT activity in cultured cells as well as immature zygotic embryos. Expression of CAT activity, which was dependent upon the DNA concentration used, could be detected as early as 20 h after bombardment. The results also suggested that the recipient cells have to be in an active state of cell division in order for the introduced gene to be expressed since mature zygotic as well as somatic embryos failed to reveal any gene expression. The effect of other parameters which influence the expression of the introduced gene as well as the potential of this novel technology for cereal transformation are also discussed. PMID- 24233523 TI - Micropropagation of Cephaelis ipecacuanha rich. AB - Shoot cultures of ipecac, Cephaelis ipecacuanha Rich. were established by inoculating seedling nodal explants onto modified Murashige and Skoog's medium supplemented with 8 mg/l kinetin, 0.05 mg/l NAA and 200 mg/l adenine. Upto 12 new axillary shoots per explant were induced after 12 weeks incubation. Shoot cultures were also established by placing shoot tips on medium containing 0.1 0.25 mg/l NAA with 8 mg/l kinetin for 4 weeks and then to shoot multiplication medium for 8 weeks. The multiplication was maintained over several passages. Shoots were rooted using 2 mg/l IBA and normal plants were re-established. PMID- 24233522 TI - Multiplication of tobacco mosaic virus in tobacco callus tissues and in vitro selection for viral disease resistance. AB - Tobacco mosaic virus-resistant tobacco was selected in vitro using callus tissues induced from axillary buds of systemically infected tobacco plants. Callus lines in which the virus was continuously multiplying were first isolated and redifferentiated into shoots. By the procedure, non-diseased, healthy shoots were successfully isolated from diseased shoots, which showed typical mosaic symptoms of the virus, and regenerated into intact plants.These regenerated plants showed resistance to virus inoculation, and selfed progeny of virus-resistant regenerants segregated the resistance and susceptibility according to the Mendelian system. PMID- 24233524 TI - Recovery of somatic embryos and plantlets from protoplast cultures of Larix * eurolepis. AB - Somatic embryos and plantlets were regenerated from protoplasts of hybrid larch (Larix * eurolepis) isolated from two embryogenic callus and cell suspension culture lines (L1 and L2). L2, which was highly embryogenic, consistently yielded protoplasts that gave rise to somatic embryos. Centrifugation on a discontinuous medium/Percoll density gradient resulted in accumulation of embryogenic protoplasts in one of the Percoll interfaces. First division frequencies were in the range of 28-39% in line 1 and 18-20% in line 2 in both liquid and agarose solidified culture media. The critical factor in maintaining high viability of cultures was lowering of osmotic pressure by dilution of the initial medium. The first somatic embryos were detected in 23- to 28-day-old cultures. Some of these developed into plants that were transferred to soil. PMID- 24233525 TI - Agrobacterium mediated transfer of chlorsulfuron resistance to commercial flax cultivars. AB - Agrobacterium tumefaciens carrying a disarmed Ti-plasmid vector containing a chimeric NPT-ll gene and a mutant acetolactate synthase gene (conferring resistance to the herbicide chlorsulfuron) from Arabidopsis was used to transform flax (Linum usitatissimum) hypocotyl tissue. Transgenic regenerants were recovered from the inoculated tissue and were tested for expression of the foreign genes by leaf callus assays on kanamycin and on chlorsulfuron. Transgenic plants were grown to maturity; selfed progeny were similarly tested to determine segregation pattern for the novel genes, and some were grown in chlorsulfuron containing soil. Lines from two major commercial cultivars express chlorsulfuron resistance in greenhouse tests. PMID- 24233526 TI - Rapid clonal propagation of Pinellia ternata by tissue culture. AB - Adventitious buds or protocorm-like bodies were regenerated directly from excised explants without intervening callus. Differences in the ability of regeneration were observed among different plant organs with bulbils showing the highest regenerative ability followed by leaf blade and petiole. Ability of vegetative propagation of bulbil could be maintained by alternate solid-and liquid-medium culture. Theoretically, 1.7*10(27) plantlets could be produced from a single bulbil by this technique within one year based on the production and rapid growth of protocorm-like bodies and adventitious buds. Concentration of MS salts, NAA and sucrose influenced not only root formation from the differentiated adventitious buds, but also root number and length. For root formation, the best combination was one-half strength MS salts with 3-5% sucrose and 1 mg/l NAA. The high survival rate of 96% was recorded when plantlets were transplanted into a mixture of vermiculite:loam soil:peat moss (1:2:1). Plants from in vitro culture were morphological similar to field-grown plants. The acute toxicity of crude extracts from protocorm-like bodies was about one-fourth that of extracts from tubers of field-grown plants when tested with white mice. Tissue culture has potential for clonal propagation of Pinellia ternata plants for commercial use. PMID- 24233527 TI - Bioreactor studies of growth and nutrient utilization in alfalfa suspension cultures. AB - Alfalfa (Medicago sativa L.) cells were grown in 500 ml, aerated and stirred batch bioreactors using Schenk and Hildebrant medium. For cultures in which the pH was allowed to vary, we observed two fairly distinct growth phases. Evidence is presented which indicates that the two-phase growth is most likely a result of the two nitrogen sources in the medium. The ammonium present in the medium is directly utilized during the first growth phase and ammonium resulting from intracellular nitrate reduction is utilized during the second phase. During the first growth phase, sucrose is completely hydrolyzed to glucose and fructose with some glucose and fructose consumption. In the second growth phase glucose is consumed preferentially over fructose. Attempts at maintaining the pH at 5.5 using 1N NaOH as the base titrant resulted in very little cell growth compared with cultures for which the pH was allowed to vary. PMID- 24233528 TI - In vitro shoot regeneration of Populus deltoides: effect of cytokinin and genotype. AB - Treatment differences were observed in the in vitro adventitious shoot regeneration response from internodal explants of three genotypes of Populus deltoides cultured on media supplemented with five concentrations each of the cytokinins 6-benzyladenine, 2-isopentyladenine, and zeatin. For each of the three genotypes, the greatest number of shoots were consistently regenerated on media containing the cytokinin zeatin. Tissue necrosis resulted when explants from any of the three genotypes were cultured on media supplemented with 6-benzyladenine. A zeatin concentration by genotype interaction was also observed. Genotypic differences in shoot regeneration were observed for 16 genotypes of Populus deltoides when cultured on medium supplemented with 0.5 mgL(-1) zeatin. Six genotypes were highly recalcitrant and failed to regenerate shoots. The percent of explants regenerating was greater than 50% for four genotypes. PMID- 24233529 TI - Effect of ethylene on sanguinarine production from Papaver somniferum cell cultures. AB - A Papaver somniferum cell line capable of producing sanguinarine equivalent to 3% of cell dry weight was used to determine if ethylene was involved in signalling the biosynthesis of this alkaloid. A 3.3-fold increase in ethylene emanation from these cell suspension cultures was observed 7 h after elicitation with a Botrytis fungal homogenate. The rate of ethylene release then decreased to near zero after 48 h, suggesting that a pulse of ethylene production may be involved in sanguinarine production. However, sanguinarine biosynthesis was not promoted when either the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), or the ethylene releasing agent, 2-chloroethylphosphonic acid (ethephon), was added to the culture. These results strongly suggest that ethylene is not intimately involved in the production of sanguinarine from Papaver somniferum cell cultures or in the transduction of the elicitation event. PMID- 24233530 TI - Anthocyanin accumulation and changes in activities of phenylalanine ammonia-lyase and chalcone synthase in roselle (Hibiscus sabdariffa L.) callus cultures. AB - Time-course changes in anthocyanin accumulation, phenylalanine ammonia-lyase activity and chalcone synthase activity were examined in roselle callus tissues incubated under different culture conditions. Phenylalanine ammonia-lyase activity was not affected by either the kind of auxin supplemented to the medium or light regime. In contrast, chalcone synthase activity was markedly suppressed when the callus was cultured with a medium containing indole-3-acetic acid instead of 2,4-dichlorophenoxyacetic acid (2,4-D) or in the dark. The results imply that in roselle callus cultures chalcone synthase plays a more important role in anthocyanin biosynthesis regulated by 2,4-D and light irradiation than phenylalanine ammonialyase. PMID- 24233531 TI - Sequential release of both basic and acidic isoperoxidases to the media of suspension cultured cells of Capsicum annuum. AB - The establishment of suspension cell cultures from trimmed cotyledons of pepper (Capsicum annuum L.) provides a new experimental system for studying the relationship between release of peroxidase (EC 1.11.1.7) into the free intercellular spaces and plant cell growth. In contrast with several other species, the total peroxidase activity in the medium increased continuously during the post-exponential growth phase of the pepper cell culture, and this was correlated with the growth inhibition of pepper cells cultivated in suspension. The increase in the peroxidase activity in the culture medium was the consequence of a differential release of isoperoxidases, prominently marked by a primary release of basic isoperoxidases, followed by a strong increase in the level of acidic isoperoxidases. Thus, pepper cells cultures constitute a new experimental system for studying the regulation of the sequential release of basic and acidic isoperoxidases, which occurs during the growth cessation of plant cells. PMID- 24233532 TI - Phenolics production by encapsulated Nicotiana tabacum cells. AB - Plant cells of tobacco (Nicotiana tabacum L.) were grown for several generations in suspension cultures. Cells were immobilized in continuous bioreactors in calcium alginate (Ca Alg) beads or in poly-L-lysine (PLL) encapsulated calcium alginatehydrogels. In each case, the cells were fed continuously a modified Linsmaier-Skoog plant cell culture medium. The bioreactor effluent was analyzed for total phenolic compounds. The net specific productivity of phenolics was calculated on a daily basis for several test runs. For comparison, productivity in suspension cultures was monitored. Productivity of suspended cells declined to zero within 9 d; both immobilized and encapsulated cells remained productive for 16 d following inoculation. Specific productivity by encapsulated cells was higher than that by immobilized cells; in both types similar rates of decline in productivity occurred. PMID- 24233533 TI - Comparison of secondary product accumulation in photoautotrophic, photomixotrophic and heterotrophic Nicotiana tabacum cell suspension cultures. AB - Photoautotrophic, photomixotrophic and heterotrophic Nicotiana tabacum cell suspension cultures were compared for the constitutive accumulation of secondary metabolites and the elicitor-induced formation of the phytoalexin capsidiol. Nicotine and chlorogenic acid were found in high amounts in the heterotrophic cultures and in moderate concentrations in photomixotrophic but not in photoautotrophic cells. Nicotinic acid-N-glucoside occured in all culture types; in photoautotrophic and photomixotrophic cells the formation of N-methylnicotinic acid (trigonelline) was also observed. Treatment with a fungal elicitor led to substantial accumulation of capsidiol in heterotrophic and photomixotrophic cells and in only low levels in photoautotrophic cultures. Elicitor-treated photomixotrophic cells showed a pronounced increase in cell wall-bound phenolics. The levels of nicotine, nicotinic acid-N-glucoside and trigonelline were not affected by elicitation. PMID- 24233534 TI - High frequency plant regeneration of Cymbopogon martinii (Roxb.) Wats by somatic embryogenesis and organogenesis. AB - Embryogenic callus cultures were obtained upon repeated sub-culture of non embryogenic callus from nodal segments of Cymbopogon martinii (Roxb.) Wats. Murashige and Skoog's medium supplemented with 1mg/l 2,4-dichlorophenoxyacetic acid and 0.5 mg/l kinetin and Linsmaier and Skoog's medium supplemented with 2mg/l 2,4-dichlorophenoxyacetic acid and 0.4 mg/l kinetin were used as maintenance media for non-embryogenic and embryogenic cultures, respectively. Plant regeneration occurred through organogenesis in MS basal media containing 2 mg/l kinetin, 1 mg/l 6-benzylaminopurine, 0.2 mg/l biotin, 0.2 mg/l Ca pantothonate and 0.1 mg/l napthalene acetic acid. Embryogenesis was induced in LS medium supplemented with 1 mg/l kinetin, 0.5 mg/l 6-benzylaminopurine and 0.1 mg/l 3-indole acetic acid. Plant regeneration at high frequency was recorded both through organogenesis and embryogenesis in different passages of long term callus cultures. PMID- 24233535 TI - Plant regeneration from isolated microspore cultures of Chinese cabbage (Brassica campestris spp. pekinensis). AB - Isolated microspores of Chinese cabbage (Brassica campestris ssp. pekinensis) were incubated in modified NN medium containing 10% sucrose in darkness at 33 degrees C for one day followed by culture at 25 degrees C. After 14 days of culture, microspores developed into embryos ranging from globular to cotyledonary stage. Plants were regenerated after transfer of embryos to medium containing 3% sucrose and no plant growth regulators. PMID- 24233536 TI - In vitro propagation of guayule (Parthenium argentatum) - a rubber yielding shrub. AB - Nodal explants (0.5 to 0.8 cm long) isolated from 2-year old shrubs of guayule, Parthenium argentatum Gray, when cultured on MS medium supplemented with different concentrations of KN, BAP, 2,4-D, 2,4-D + BAP, NAA and NAA + BAP produced callus tissues and shoots simultaneously with varying frequencies. Shoots were regenerated with a high frequency (80-88%) from callus on MS medium containing NAA + BAP with or without glutamine. Addition of glutamine to these media improved considerably the number of shoots formed from a known amount of callus. Shoots could be regenerated from 200 day old callus cultures with a very high frequency but the organogenetic capacity declined thereafter. Increase in the concentration of sucrose (upto 4%) significantly enhanced the shoot forming ability of callus, but higher concentrations (6%) suppressed it. Rooting was induced only in dark when IAA, IBA and NAA were used, but 2,4-D could induce them both in light and dark. The system is suitable for the mass propagation of this important rubber yielding plant. PMID- 24233537 TI - Propagation of Indian Rhubarh (Rheum emodi Wall.) using shoot-tip and leaf explant culture. AB - Shoot-tip explants of Rheum emodi Wall. (Polygonaceae) gave rise to multiple shoots when cultured on a Murashige and Skoog (1962) medium (MS) with 2.0 mg/l 6 benzylaminopurine (BAP) and 1.0 mg/l indole-3-butyric acid (IBA). Also, shoot buds developed from leaf explants using MS medium with 2.0 mg/l BAP and 0.25 to 1.0 mg/l indole-3-acetic acid (IAA) or IBA. Roots were induced when the resulting shoots were placed on MS medium with 1.0 mg/l IBA. Both regeneration procedures gave rise to healthy plantlets that were established in soil under glasshouse conditions at 80% frequency after hardening phase of two weeks. Regenerated plants showed a constant chromosome number of 2n=2x=22, same as the parent plant. The use of liquid shake cultures minimized the time and culture medium requirements for propagation. This procedure can be applied for the conservation and utilization of elite clones of R. emodi. PMID- 24233538 TI - Comparative greenhouse study of Eucalyptus grandis in vitro plantlets and half sib seedlings, I. Net photosynthesis. AB - Tissue culture-derived plantlets from three superior five-year-old Eucalyptus grandis Hill ex Maid hybrids were compared to their related half-sib seedlings under greenhouse conditions. Net photosynthesis, chlorophyll a and b concentrations, and nitrogen concentration were sampled four times at 40-day intervals. Comparisons were started 40 days after plantlets and germinating seedlings were moved from mist to greenhouse conditions. Seedlings had higher net photosynthesis, chlorophyll and nitrogen concentration at early harvests. However, as the study progressed the difference between plantlets and seedlings decreased and reached similar values. No family differences were observed regardless of plant origin (seedlings or plantlets). Plantlets and seedlings showed similar general trends in all the measured parameters over the four harvests. PMID- 24233539 TI - Comparative greenhouse study of Eucalyptus grandis in vitro plantlets and half sib seedlings, II. Dry matter accumulation and relative distribution. AB - In vitro directly micropropagated plantlets from three selected five-year-old Eucalyptus grandis Hill ex. Maiden hybrids were compared to their related half sib seedlings for growth and growth pattern parameters under greenhouse conditions used for operational seedling production. The oven dry weights were determined from stem, leaf, and root samples collected every 40 days for four times. Relative growth rate, net assimilation rates and shoot:root ratio were calculated. Survival was 98% and 95% for plantlets and seedlings, respectively. Significant differences were observed between parents in terms of shoot and root dry weights and their ratios with similar ranking among plantlets and seedlings, suggesting genetic control over these traits. Plantlets started with significantly higher root: shoot ratios and stem, leaf, root, and total dry weight. Although seedlings had higher relative growth and net assimilation rates, all the initial differences decreased sharply over time. PMID- 24233540 TI - Defense gene expression in elicitor-treated cell suspension cultures of french bean cv. Imuna. AB - Cell suspension cultures of bean (Phaseolus vulgaris) cv. Imuna accumulated isoflavonoid phytoalexins on exposure to elicitor from the phytopathogenic fungus Colletotrichum lindemuthianum (CL). This was preceeded by rapid increases in the activities of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS). However, the patterns of expression of PAL and CHS genes differed from those observed in cultures of a previously studied bean cultivar. The relative levels of transcripts from individual members of the CHS multigene family differed significantly at 1.5 h compared to 22.5 h after elicitation. More strikingly, three PAL genes were expressed in cultivar Imuna in response to fungal elicitor, whereas two are expressed in elicitor-treated cell cultures of cultivar Canadian Wonder. PMID- 24233541 TI - How to avoid unbounded drug accumulation with fractional pharmacokinetics. AB - A number of studies have shown that certain drugs follow an anomalous kinetics that can hardly be represented by classical models. Instead, fractional-order pharmacokinetics models have proved to be better suited to represent the time course of these drugs in the body. Unlike classical models, fractional models can represent memory effects and a power-law terminal phase. They give rise to a more complex kinetics that better reflects the complexity of the human body. By doing so, they also spotlight potential issues that were ignored by classical models. Among those issues is the accumulation of drug that carries on indefinitely when the infusion rate is constant and the elimination flux is fractional. Such an unbounded accumulation could have important clinical implications and thus requires a solution to reach a steady state. We have considered a fractional one compartment model with a continuous intravenous infusion and studied how the infusion rate influences the total amount of drug in the compartment. By taking an infusion rate that decays like a power law, we have been able to stabilize the amount of drug in the compartment. In the case of multiple dosing administration, we propose recurrence relations for the doses and the dosing times that also prevent drug accumulation. By introducing a numerical discretization of the model equations, we have been able to consider a more realistic two-compartment model with both continuous infusion and multiple dosing administration. That numerical model has been applied to amiodarone, a drug known to have an anomalous kinetics. Numerical results suggest that unbounded drug accumulation can again be prevented by using a drug input function that decays as a power law. PMID- 24233542 TI - Comparative-high resolution melting: a novel method of simultaneous screening for small mutations and copy number variations. AB - Efficient and cost-effective screening for DNA sequence changes, both small mutations and copy number variations (CNVs), is a crucial aspect for routine genetic diagnostics as well as for basic research. In this study we present a development and evaluation of comparative-high resolution melting (C-HRM), a new approach for the simultaneous screening of small DNA changes and gene CNVs. In contrast to other methods, relative quantification in C-HRM is based on the results obtained during the melting process and calculations of the melting peak height ratio in the multiplex reaction. Validation of the method was conducted on DNA samples from 50 individuals from Duchenne muscular dystrophy (DMD) families, 50 probands diagnosed with familial adenomatous polyposis and a control group of 36 women and 36 men. The results of analyses conducted on fragments of the DMD and APC genes correspond completely (100 %) with the results of previous studies. C-HRM sensitivity in CNV detection was assessed through the analysis of mixed DNA samples with different proportions of a deletion carrier and wild type control. The results are presented as a linear regression with R 2 of 0.9974 and imply the capability of the method to detect mosaics. C-HRM is an attractive and powerful alternative to other methods of point mutations and CNV detection with 100 % accuracy in our studied group. PMID- 24233543 TI - Poly(HEMA-co-NBMI) monolithic cryogel columns for IgG adsorption. AB - Supermacroporous poly(2-hydroxyethyl methacrylate-co-1,5-naphthalene bismaleimide) [poly(HEMA-co-NBMI)] monolithic cryogel column was prepared by free radical cryo-copolymerization of HEMA with NBMI as a hydrophobic functional comonomer and N,N'-methylene-bisacrylamide as cross-linker directly in a plastic syringe for adsorption of albumin. The monolithic cryogel contained a continuous polymeric matrix which has interconnected pores of 10-100 MUm size. Poly(HEMA-co NBMI) cryogel was characterized by swelling studies, FTIR and scanning electron microscopy. The equilibrium swelling degree of the poly(HEMA-co-NBMI) cryogel was 10.5 g of H2O/g dry cryogel. Poly(HEMA-co-NBMI) cryogel was used in the adsorption/desorption of IgG from aqueous solutions. The maximum amount of IgG adsorption from aqueous solution in phosphate buffer was 98.20 mg/g polymer at pH 7.0. The nonspecific adsorption of IgG onto plain poly(HEMA) cryogel was very low (2.79 g/g polymer). It was observed that IgG could be repeatedly adsorbed and desorbed with the poly(HEMA-co-NBMI) cryogel without significant loss of adsorption capacity. PMID- 24233544 TI - Enhancement of stress tolerance in the polyhydroxyalkanoate producers without mobilization of the accumulated granules. AB - Poly(3-hydroxybutyrate) [P(3HB)], a polymer belonging to the polyhydroxyalkanoate (PHA) family, is accumulated by numerous bacteria as carbon and energy storage material. The mobilization of accumulated P(3HB) is associated with increased stress and starvation tolerance. However, the potential function of accumulated copolymer such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] remained unknown. In this study, Delftia acidovorans DS 17 was used to evaluate the contributions of P(3HB) and P(3HB-co-3HV) granules during simulated exogenous carbon deprivation on cell survival by transferring cells with PHAs to carbon free mineral salt medium supplemented with 1% (w/v) nitrogen source. By mobilizing the intracellular P(3HB) and P(3HB-co-3HV) at 11 and 40 mol% 3HV compositions, the cells survived starvation. Surprisingly, D. acidovorans containing P(3HB-co-94 mol% 3HV) also survived although the mobilization was not as effective. Similarly, recombinant Escherichia coli pGEM-T::phbCAB(Cn) (harboring the PHA biosynthesis genes of Cupriavidus necator) containing P(3HB) granules had a higher viable cell counts compared to those without P(3HB) granules but without any P(3HB) mobilization when exposed to oxidative stress by photoactivated titanium dioxide. This study provided strong evidence that enhancement of stress tolerance in PHA producers can be achieved without mobilization of the previously accumulated granules. Instead, PHA biosynthesis may improve bacterial survival via multiple mechanisms. PMID- 24233545 TI - Discovery, identification and sequence analysis of RNAs selected for very short or long poly A tail in immature bovine oocytes. AB - A major challenge in applying genomics to oocyte physiology is that many RNAs are present but will not be translated into proteins, making it difficult to draw conclusions from RNAseq and array data. Oocyte maturation and early embryo development rely on maternal storage of specific RNAs with a short poly(A) tail, which must be elongated for translation. To resolve the role of key genes during that period, we aimed to characterize both extremes of mRNA: deadenylated RNA and long polyA tails mRNA population in immature bovine oocytes. Using magnetic beads coupled to oligodT, we isolated deadenylated (A-, 20-50 adenosines) from polyadenylated (A+, up to 200 adenosines) RNAs. After transcriptomic analysis, we observed that A+ candidates are associated with short-term processes required for immediate cell survival (translation or protein transport) or meiotic resumption, while several A- candidates are involved in processes (chromatin modification, gene transcription and post-transcriptional modifications) that will be extremely important in the development of the early embryo. In addition to a list of candidates probably translated early or late, sequence analysis revealed that cytoplasmic polyadenylation element (CPE) and U(3)GU(3) were enriched in A- sequences. Moreover, a motif associated with polyadenylation signals (MAPS, U(5)CU(2)) appeared to be enriched in 3'untranslated regions (UTR) with CPE or U(3)GU(3) sequences in bovine but also in zebrafish and Xenopus tropicalis. To further validate our methodology, we measured specific tail length of known candidates (AURKA, PTTG1, H2A1) but also determined the poly(A) tail length of other candidate RNAs (H3F3A, H1FOO, DAZAP2, ATF1, ATF2, KAT5, DAZL, ELAVL2). In conclusion, we have reported a methodology to isolate deadenylated from polyadenylated RNAs in samples with small total RNA quantities such as mammals. Moreover, we identified deadenylated RNAs in bovine oocytes that may be stored for the long-term process of early embryo development and described a conserved motif enriched in the 3'UTR of deadenylated RNAs. PMID- 24233546 TI - The study of mammalian oocyte competence by transcriptome analysis: progress and challenges. AB - Various morphological and cytological traits of oocytes and their surrounding cumulus cells may be used to select oocytes for assisted reproduction. However, even with careful selection, successful IVF and subsequent embryo development remain uncertain. The factors that ensure oocyte competence are unclear and other approaches to assessing developmental potential must be explored. With the constant development of the molecular toolbox, genomic/transcriptomic analysis is becoming a more and more interesting approach to understand oocyte quality on the basis of RNA composition. Using bovine and mouse models as well as human oocytes of known developmental potential, various efforts are underway to characterize the mRNA profile of the competent oocyte using microarray technology. The proliferation of gene expression data sets raises new opportunities to identify the mechanisms involved in this complex phenotype, which should lead to improved techniques of assisted reproduction. Although several molecular markers of oocyte quality are known, translating these into cellular functions remains challenging, largely due to the poor correlation between mRNA level and protein synthesis. Unlike most somatic cells, the oocyte can store mRNA for days, with transcriptional activity remaining at a halt during the 4-5 days beginning before ovulation and ending with embryonic genome activation. This review provides an overview of the transcriptomic data obtained from oocytes of different quality as well as interesting avenues to explore in order to improve our understanding of oocyte competence. PMID- 24233547 TI - Current trends in slot machine gambling: Research and policy issues. AB - This paper introduces a special issue of theJournal of Gambling Studies on slot machine gambling, and overviews some current trends concentrating on research and policy issues. It is demonstrated that throughout the world, research findings have linked slot machines with pathological gambling. Indeed slot machines are now the predominant form of gambling activity by pathological gamblers treated in self help groups and professional treatment centres in numerous countries. This paper briefly examines the research on slot machines and pathological gambling and then goes on more specifically to examine four areas. These are (i) slot machine gambling and youth, (ii) slot machines and arcade video game playing, (iii) the possible developmental link between slot machines and video games and (iv) pathological video game playing. PMID- 24233548 TI - Pathological gambling: A comparison of gambling at German-style slot machines and "Classical" gambling. AB - German-style slot machines and related legal issues are described. On the basis of a survey on 437 members of self-help groups (Gamblers Anonymous) in Germany, slot machine gamblers were compared with casino gamblers on such variables as sociodemographic data, gambling behaviour, financial expenditure, emotional experience while gambling, symptoms of pathological gambling, psychosocial consequences and gambling related delinquency. The casino gamblers' gambling behaviour is financially more extensive. There were similarities regarding the emotional intensity of the gambling experience. However the casino gamblers show more pronounced symptoms of pathological gambling and the psychosocial consequences of their gambling behaviour are more severe. In spite of these differences, the data show that for young people slot machines can be as stimulating and therefore as dangerous as casino gambling. The young slot machine gambler runs a similar risk of acquiring a pathological gambling habit as the casino gambler. PMID- 24233549 TI - Slot machine gambling in Spain: An important and new social problem. PMID- 24233550 TI - Video game playing, dependency and delinquency: A question of methodology? AB - A methodological challenge to Fisher's (1992) study of adolescent fruit machine gamblers was carried out with young video game players. Fisher (1992) described an association between frequency fruit machine playing, dependency and delinquency. Some methodological concerns were considered that might weaken this conclusion, in particular the use of heterogeneous measures that fail to distinguish between variables. As such measures feature elsewhere in contemporary gambling research it was deemed important to examine some of the potential problems that may arise. 183 11-16 year old video game players (152 males; 31 females) were recruited from four amusement arcades to answer a computerised questionnaire. Using an analysis similar to Fisher (1992) her results for adolescent fruit machine use were 'confirmed'. However a separation of key variables and the use of a multiple regression analysis showed that of money spent, time spent and impaired choice, only the first was a significant predictor of delinquency. It is suggested that delinquents have higher disposable incomes to spend on their leisure activities. Video game playing and possibly fruit machine gambling appear to be independently associated with delinquency; in video game playing this association is not mediated by dependency. It was argued that a similar methodology should be used in the UK to re-examine Fisher's (1992) conclusions for children who use gaming machines. PMID- 24233551 TI - Adolescent slot machine dependency and delinquency: Questions on a question of methodology. AB - This paper responds to Abbott, Palmisano and Dickersons' methodological challenge to Fisher's (1992) study of adolescent fruit machine gamblers, carried out with young video game players. It is argued that important differences in the game under study, the measure of 'pathological gambling' used and sample characteristics seriously undermine the extent to which a comparison and extrapolation of findings are achieved. In the analysis which follows, the author wishes to highlight areas of constructive criticism as well as limitations to the challenge with the aim of progressing academic endeavour in this important field. PMID- 24233552 TI - "Minnesota slots": An observational study of pull tab gambling. AB - A study of pull tab gambling in Minnesota was undertaken to describe the state's most popular form of gambling. The study also focused on the detection of any abuses or addictive problems that might be associated with it. Pull tab gambling is similar to slot machine gambling. The game, fundamentals of play, and some of the behaviors of pull tab gamblers are described. Various playing patterns and strategies, pull tab etiquette, the numbers and types of players, amounts of money bet, player's wins and losses, house profits, gambling abuses, behaviors which may indicate problem gambling, and dealer/player relationships are discussed. The study concludes with suggestions to help minimize some of the actual and potential problems and abuses that accompany pull tab gambling. PMID- 24233553 TI - Towards a risk factor model of fruit machine addiction: A brief note. PMID- 24233554 TI - Effects of bioaugmentation on enhanced reductive dechlorination of 1,1,1 trichloroethane in groundwater: a comparison of three sites. AB - Microcosm studies investigated the effects of bioaugmentation with a mixed Dehalococcoides (Dhc)/Dehalobacter (Dhb) culture on biological enhanced reductive dechlorination for treatment of 1,1,1-trichloroethane (TCA) and chloroethenes in groundwater at three Danish sites. Microcosms were amended with lactate as electron donor and monitored over 600 days. Experimental variables included bioaugmentation, TCA concentration, and presence/absence of chloroethenes. Bioaugmented microcosms received a mixture of the Dhc culture KB-1 and Dhb culture ACT-3. To investigate effects of substrate concentration, microcosms were amended with various concentrations of chloroethanes (TCA or monochloroethane [CA]) and/or chloroethenes (tetrachloroethene [PCE], trichloroethene [TCE], or 1,1-dichloroethene [1,1-DCE]). Results showed that combined electron donor addition and bioaugmentation stimulated dechlorination of TCA and 1,1 dichloroethane (1,1-DCA) to CA, and dechlorination of PCE, TCE, 1,1-DCE and cDCE to ethane. Dechlorination of CA was not observed. Bioaugmentation improved the rate and extent of TCA and 1,1-DCA dechlorination at two sites, but did not accelerate dechlorination at a third site where geochemical conditions were reducing and Dhc and Dhb were indigenous. TCA at initial concentrations of 5 mg/L inhibited (i.e., slowed the rate of) TCA dechlorination, TCE dechlorination, donor fermentation, and methanogenesis. 1 mg/L TCA did not inhibit dechlorination of TCA, TCE or cDCE. Moreover, complete dechlorination of PCE to ethene was observed in the presence of 3.2 mg/L TCA. In contrast to some prior reports, these studies indicate that low part-per million levels of TCA (< 3 mg/L) in aquifer systems do not inhibit dechlorination of PCE or TCE to ethene. In addition, the results show that co-bioaugmentation with Dhc and Dhb cultures can be an effective strategy for accelerating treatment of chloroethane/chloroethene mixtures in groundwater, with the exception that all currently known Dhc and Dhb cultures cannot treat CA. PMID- 24233555 TI - CD30: from basic research to cancer therapy. AB - The FDA recently approved an agonistic anti-CD30 drug conjugate, Brentuximab vedotin, for the treatment for CD30-positive lymphomas. The potent clinical activity of Brentuximab vedotin in Hodgkin's lymphoma and anaplastic large-cell lymphoma was greeted with great enthusiasm by oncologists as it provided a new treatment modality for these diseases. In this review, we will describe how we obtained the hybridoma by pursuing a basic research experiment unrelated to CD30. I will also review what we know about the normal biological functions of CD30 that were studied primarily in murine models of disease but also in patients. The picture emerging is that one of the primary functions of CD30 is the control of memory cells providing costimulation and trafficking information or inducing apoptosis in a microenvironment and cytokine milieu-dependent manner. PMID- 24233556 TI - The glutathione S-transferases of fish. AB - Substantial soluble glutathione S-transferase activity and millimolar reduced glutathione (GSH) are present in most tissues of both teleosts and elasmobranchs. The hepatic enzymes of fish conjugate a range of electrophilic substrates with GSH, although their specificities are less broad than those of the transferases in rodent liver. There is no good evidence that fish transferases have ligandin like activity or a 'suicide' function. All fish livers tested have several transferase isoenzymes. They are dimers of subunits whose Mrs are about 25 kDa and which may have different catalytic properties. In some species transferase activity is induced by agents such as phenols or 3-methylcholanthrene. Glutathione S-transferases are important detoxication enzymes in fish. PMID- 24233557 TI - Iron catalyzed oxidation of trout diets and its effect on the growth and physiological response of rainbow trout. AB - Two experiments were conducted to determine 1) the effect of iron supplementation and the quality of fish oils on dietary lipid peroxidation and 2) the concurrent effects of diet rancidity and iron overload on the growth and physiological response of rainbow trout. Semi-purified diets supplemented with graded levels of iron (0-6250 mg/kg diet as ferrous sulphate) were fed to trout for 12-36 weeks. The malonaldehyde (MA) concentration of the test diets increased as the iron levels in the diets increased indicating that iron catalyzed lipid oxidation was occurring. However, when ethoxyquin was added to the oils, the increase in dietary MA level was significantly reduced. Fish oils with an initial high peroxide value were more susceptible to iron-catalyzed lipid oxidation. The concurrent effects of diet rancidity and iron overload (greater than 86 mg/kg) led to the development of unique histopathological signs, poor growth and high mortalities in the trout. In contrast, when diet rancidity was low (less than 10 ug MA/g diet), the toxic level of dietary iron was greater than 1380 mg/kg diet. The concentration of iron in trout tissues, and the hematocrit and hemoglobin concentrations increased as dietary iron levels increased and were not affected by the degree of diet rancidity. PMID- 24233558 TI - Responses to prolonged hypoxia by rainbow trout (Salmo gairdneri) I. Free amino acids and proteins in plasma, liver and white muscle. AB - In order to estimate the mobilization of nitrogen compounds for energetic purposes in trout under hypoxic conditions, commercial-size rainbow trout, acclimated to 15 degrees C, were maintained for 10 weeks at an oxygen level of 5.3 +/- 0.5 mg/l ('hypoxic' group) or 8.4 +/- 0.4 mg/I (control group), and the changes in tissue concentrations of free amino acids and proteins studied. In animals subjected to hypoxia, there was a decrease in plasma free amino acids involved in gluconeogenesis, liver alanine and aspartic acid, plasma and liver protein concentrations, and muscle free histidine. These results suggest a trend of rainbow trout metabolic activity towards energy production at the expense of anabolism when oxygen availability in water is limited over a long period of time. PMID- 24233559 TI - Changes in tissue lipid levels in the freshwater catfishClarias batrachus associated with the reproductive cycle. AB - The levels of free fatty acid (FFA), monoglyceride (MG), diglyceride (DG), triglyceride (TG), phospholipid (PL), free cholesterol (CF) and esterified cholesterol (CE) were measured in the liver, plasma, ovary, abdominal fat and muscle during different phases of the annual reproductive cycle in femaleClarias batrachus. During the preparatory phase, hepatic lipogenic activity predominated over mobilization and consumption. In the prespawning season, an increased hepatic lipogenic activity was maintained, but lipids were transferred from the liver to the ovary. In the spawning phase, the diminished food intake, and enhanced caloric demand for spawning behaviour and activity limited hepatic lipogenic activity, and TG lypolysis was increased as was the production of more FFA. Maximum accumulation of vitellogenin, as reflected by maximum rise in ovarian PL titre was characteristic of this phase. Marked reductions in ovarian lipid occurred during the postspawning phase. In the resting phase, there was a recovery of lipogenic activity, but PL synthesis was still inhibited. In contrast to other investigated teleosts, there were extremely high level of FFA in liver, plasma, ovary and muscle throughout the annual reproductive cycle inC. batrachus. FFA appears to be the main lipid metabolite which had a very high turnover. As evidenced by the high TG content, abdominal fat seems to be the main fat depot, not the liver and muscle. PMID- 24233560 TI - Hormonal changes during meiotic maturation and ovulation in the brook trout (Salvelinus fontinalis). AB - The plasma levels of estradiol-17beta (E2), 17alpha, 20beta-dihydroxy-4-pregnen-3 one (17,20-P) and gonadotropin (GTH) were measured in brook trout (Salvelinus fontinalis) during the period from the end of vitellogenesis to postovulation. Blood samples were taken according to specific stages of maturation, including germinal vesicle breakdown (GVBD) and ovulation. E2 levels were quite high (~45 ng/ml) at the end of vitellogenesis (and prior to GVBD) and dropped precipitously by GVBD (~2 ng/ml). They remained low through ovulation and postovulation. 17,20 P levels were low prior to GVBD (~0.7 ng/ml) and increased dramatically at GVBD (~148 ng/ml). The levels of 17,20-P remained high at ovulation (~142 ng/ml) and then dropped significantly within 24 h to approximately half of the ovulatory values. They decreased even further by 7 days postovulation. GTH levels rose gradually through GVBD and ovulation from a postvitellogenic level of approximately 3 ng/ml to a 7 day postovulatory value of approximately 10 ng/ml. The overall results; 1) decrease in estradiol prior to GVBD, 2) increase in 17,20 P at GVBD and 3) gradual GTH rise through GVBD and ovulation, are similar to those reported for other salmonids. PMID- 24233563 TI - Disturbance and reattachment behavior of sea anemonesCalliactis tricolor (Le Sueur): Temporal, textural and chemical mediation. AB - Two hermit crabs,Dardanus venosus (Milne-Edwards) andPagurus pollicaris Say, have evolved mutualistic symbiotic relationships with sea anemones,Calliactis tricolor (Le Sueur). Anemones live on gastropod shells occupied by the crabs. Both partners are thought to participate in the transfer of the anemone to the crab's shell. However, neither species invariably exhibits transfer behavior when in contact with the other symbiont. Factors influencing transfer activity ofC. tricolor were studied. Anemone attachment is stimulated by disturbance and is time dependent. Anemones attached to shells more frequently immediately after the anemone was disturbed. Assays testing surface texture and surface composition showed that attachment activity of the sea anemone is dependent upon the organic matrix of the shell and is enhanced by texture. Attachment by anemones to shells with organic matrix removed is reduced, but is stimulated by adsorption of complex odor mixtures. Anemones respond to odor mixtures that signal food to crabs and to odor mixtures that stimulate shell investigation and shell switching in crabs. Thus,C. tricolor participates in shell transfer activity after disturbance. Behavior of the anemone is cued by texture and chemicals, including chemical mixtures that cause hermit crabs to change shells. PMID- 24233562 TI - Mouse organic cation transporter 1 determines properties and regulation of basolateral organic cation transport in renal proximal tubules. AB - The proximal tubule of mouse kidney expresses mouse organic cation transporter 1 (mOCT1), mOCT2, and much less mOCT3. Therefore, mOCT-mediated transport across the basolateral membrane of proximal tubules reflects properties of at least mOCT1 and mOCT2. Here, we unraveled substrate affinities and modulation of transport activity by acute regulation by protein kinases on mOCT1 and mOCT2 separately and compared these findings with those from isolated proximal tubules of male and female mOCT2-/- mice. These data are also compared to our recent reports on isolated tubules from wild-type and mOCT1/2 double knockout (mOCT1/2-/ ) mice. OCT-mediated transport in proximal tubules of mOCT2-/- mice was only 20 % lower compared to those isolated from wild-type mice. While mOCT1 was regulated by all five pathways examined [protein kinase A (PKA), protein kinase C (PKC), p56lck, phosphoinositide 3-kinase (PI3K), and calmodulin (CaM)], mOCT2 activity was modulated by PKA, p56lck, and CaM only, however, in the same direction. As mOCT-mediated transport across the basolateral membrane of mOCT2-/- mice expressing only mOCT1 and to a small amount mOCT3 was identical to that observed for tubules isolated from wild-type mice and to that observed for human embryonic kidney 293 (HEK293) cells stably expressing mOCT1, mOCT1 represents the relevant paralog for OCT-dependent organic cation transport in the mouse kidney. Gender does not play a major role in expression and activity of renal OCT-mediated transport in the mouse. Properties of mouse OCT considerably differ from those of rat or human origin, and thus, observations made in these rodents cannot directly be transferred to the human situation PMID- 24233564 TI - Novel type of sex pheromone structure identified fromStigmella malella (Stainton) (Lepidoptera: Nepticulidae). AB - Short-chain unsaturated chiral methyl carbinols are identified as a new class of lepidopteran pheromone components. The natural female-produced pheromone of the banded apple pigmyStigmella malella (=Nepticula malella) (Stainton) (Lepidoptera: Nepticulidae) was identified to be a mixture of (S)-(E)-6,8-nonadien-2-ol and (S) (Z)-6,8-nonadien-2-ol. For monitoring traps, a 10:3E:Z blend at 100-1000 ug is recommended. It is suggested that pheromones with similar structures may be specific to Nepticulidae and other related microlepidopteran families. PMID- 24233561 TI - Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats. AB - Microgravity induces a redistribution of blood volume. Consequently, astronauts' body pressure is modified so that the upright blood pressure gradient is abolished, thereby inducing a modification in cerebral blood pressure. This effect is mimicked in the hindlimb unloaded rat model. After a duration of 8 days of unloading, Ca2+ signals activated by depolarization and inositol-1,4,5 trisphosphate intracellular release were increased in cerebral arteries. In the presence of ryanodine and thapsigargin, the depolarization-induced Ca2+ signals remained increased in hindlimb suspended animals, indicating that Ca2+ influx and Ca2+-induced Ca2+ release mechanism were both increased. Spontaneous Ca2+ waves and localized Ca2+ events were also investigated. Increases in both amplitude and frequency of spontaneous Ca2+ waves were measured in hindlimb suspension conditions. After pharmacological segregation of Ca2+ sparks and Ca2+ sparklets, their kinetic parameters were characterized. Hindlimb suspension induced an increase in the frequencies of both Ca2+ localized events, suggesting an increase of excitability. Labeling with bodipy compounds suggested that voltage-dependent Ca2+ channels and ryanodine receptor expressions were increased. Finally, the expression of the ryanodine receptor subtype 1 (RyR1) was increased in hindlimb unloading conditions. Taken together, these results suggest that RyR1 expression and voltage-dependent Ca2+ channels activity are the focal points of the regulation of Ca2+ signals activated by vasoconstriction in rat cerebral arteries with an increase of the voltage-dependent Ca2+ influx. PMID- 24233565 TI - Identification of a novel moth sex pheromone inEriocrania cicatricella (Zett.) (Lepidoptera: Eriocraniidae) and its phylogenetic implications. AB - Extracts from different body parts of adult femaleEriocrania cicatricella (Zett.) were tested for electrophysiological activity on conspecific male antennae. Extracts from the Vth abdominal segment, containing a pair of exocrine glands, elicited the largest electroantennographic response when compared to extracts of other body parts. Female extracts were analyzed by gas chromatography with simultaneous flame ionization and electroantennographic detection (EAD). The EAD active peaks were identified as (Z)-4-hepten-2-one, (2R)-heptane-2-ol, and (2R) (Z)-4-hepten-2-ol by coinjection on a gas chromatography and by comparison of mass spectra with those of synthetic standards. In field tests, a blend of these three pheromone components was highly attractive to conspecific males, and a subtractive assay confirmed that the unsaturated alcohol is the major pheromone component, whereas no definite behavioral activity could be assigned to the ketone or the saturated alcohol. A bait containing the two alcohols withS configuration was attractive to maleE. sparrmannella (Bosc), whereas no males ofE. cicatricella were found in these traps. The sex pheromone compounds inE. cicatricella are chemically similar to pheromones reported in Trichoptera and they are produced in homologous glands. PMID- 24233566 TI - Comparison of three methods for quantifying brown algal polyphenolic compounds. AB - Three methods of quantifying total phenolic compounds in marine brown algae were compared for their ability to measure accurately known concentrations of phloroglucinol in the presence of a protein, bovine serum albumin (BSA). These methods were: (1) a Folin-Ciocalteu assay for compounds dissolved in 80% methanol, (2) a Folin-Ciocalteu assay for compounds dissolved in 75% methanol-25% trichloroacetic acid, and (3) an assay in which polyvinylpolypyrrolidone (PVPP) was used to remove phenolic compounds in order to quantify nonphenolic, Folin Ciocalteu-reactive materials. The Folin-Ciocalteu assay used with compounds dissolved in 80% methanol was the method that produced the most consistent results. It was also the assay in which the presence of proteins interfered least with the measurements of phloroglucinol and the assay that was easiest to conduct. The presence of TCA decreased the pH of the extracting solution and increased the amounts of proteins in solution. These proteins later interfered with the Folin-Ciocalteu reaction. TCA effectively bound proteins when protein concentrations were low but not when protein concentrations were high. The amount of phloroglucinol removed by PVPP varied widely and was dependent on phloroglucinol concentration, making this an unreliable method for quantifying phenolic concentrations. The Folin-Ciocalteu assay will measure some nonphenolic substances when brown algae are extracted in 80% methanol; however, inFucus gardneri, nonphenolic substances were at most 5% of the material quantified by the assay. PMID- 24233567 TI - Production of pheromone by hairpencil glands of males obtained from interspecific hybridization betweenHeliothis virescens andH. subflexa (Lepidoptera: Noctuidae). AB - Pheromone produced by the hairpencil glands of interspecific hybrid- and backcross-generation males from crosses betweenHeliothis virescens (F.) withH. subflexa (Gn.) was studied. Males of reciprocal F1 hybrids, all of which had hairpencil glands morphologically similar to those ofH. virescens, produced neither the same pheromone blend nor amounts of pheromone that were produced by males ofH. virescens. Instead, these hybrid males produced pheromone that was quantitatively and qualitatively similar to that produced byH. subflexa. Hairpencil gland extracts from males obtained from backcrossing F1 females of either cross to males ofH. subflexa were the same as those ofH. subflexa. However, extracts from backcross males of crosses between F1 females andH. virescens were variable. Some extracts from these backcross males were like those ofH. virescens while others were either likeH. subflexa or were intermediate between those of the parent species. These results showed that the production of pheromone by the hairpencil glands of hybrid and backcross males is under the dominant regulation of autosomal genes of theH. subflexa genome. PMID- 24233568 TI - Structure-activity relationship observations oftrans-trimedlure enantiomers. AB - tert-Butyl 4- (and 5-) chloro-trans-2-methylcyclohexane-1-carboxylate (TML), a mixture of four majortrans and four minorcis isomers, is used as an attractant for detecting and monitoring the male Mediterranean fruit fly (medfly),Ceratitis capitata (Wiedemann). The eight isomers (racemic mixtures) were isolated by HPLC, and their relative attractiveness in the field was determined. A quantitative structure-activity relationship (QSAR) was proposed that related a molecular measurement (A(3)) of the TML structure to male medfly captures. More recently, thetrans-TML enantiomers were synthesized in sufficient quantities for field testing. This paper reports the computer-aided molecular modeling, via Chem-X, of thetrans-TML enantiomers and the staggered and superimposed fitting with the most attractive isomer, (1S,2S,4R)-TML-C, to determine common volumes and surface areas from Van der Waals (VdW) maps. Observations of structure-activity relationships (SAR) are reported for the staggered fittings. PMID- 24233569 TI - Effects of fertility on biomass, phytotoxicity, and allelochemical content of cereal rye. AB - Studies were conducted to evaluate biomass production, tissue phytotoxicity, and allelochemical content of rye (Secale cereale L.) shoots grown in three fertility regimes (low, medium or high) in the greenhouse. Wheeler rye or a polyculture of rye and hairy vetch (Vicia villosa Roth) grown with high fertility produced the greatest biomass (78.7 and 82.7 g), with the lowest root-to-shoot ratio (0.22 and 0.43) produced in the high-fertility treatments. The polyculture treatment grown with low fertility had a greater proportion of hairy vetch (18%) than when grown with high fertility (6%). Rye shoot residue phototoxicity was affected by fertility regime. Radicle elongation of cress (Lepidium sativum L.) and barnyardgrass [Enchinochloa crus-galli (L.) Beauv. I was inhibited by rye shoot residues in a modified Parker bioassay. Rye shoot residue grown with low fertility was less inhibitory to cress radicle elongation than rye residue from the medium- or high-fertility regimes. Extracts of dried rye shoots grown with high fertility were less inhibitory than extracts from other fertility regimes. The concentrations of ether extracts of rye causing 50% inhibition (I50) of cress radicle elongation were between 125 and 276 ug/ml for greenhouse-grown and 60 and 138 ug/ml for the field-grown rye shoots. The major phytotoxic compounds in the rye shoot extracts were identified as DIBOA and BOA. The concentration of DIBOA in the greenhouse-grown rye shoots ranged between 128 and 423 ug/g while BOA concentration ranged between 2.5 and 31 ug/g. DIBOA and BOA levels were lowest in rye shoots grown with high fertility. Correlations between rye shoot biomass, DIBOA and BOA concentration, and cress barnyardgrass radicle length were significant. PMID- 24233570 TI - Response ofNp mutant of pea (Pisum sativum L.) to pea weevil (Bruchus pisorum L.) oviposition and extracts. AB - TheNp mutant of pea (Pisum sativum L.) is characterized by two physiological responses: growth of callus under pea weevil (Bruchus pisorum L., Coleoptera: Bruchidae) oviposition on pods, and formation of neoplastic callus on pods of indoor-grown plants. Although these two responses are conditioned byNp, they are anatomically and physiologically distinguishable, based on sites of origin, distribution pattern, and sensitivity to plant hormones. Further characterization of the response to extracts of pea weevil showed that response of excised pods, measured by callus formation, was log-linear, and treatment with as little as 10( 4) weevil equivalents produced a detectable response. Mated and unmated females contained similar amounts of callus-inducing compound(s), and immature females contained significantly less of the compound(s). Female vetch bruchids (Bruchus brachialis F., Coleoptera: Bruchidae), a related species, contained callus inducing compound(s), but usually less than pea weevils on a per weevil basis. Males of both species contained less than 10% of the activity of the mature females. Extracts of female black vine weevils, a nonbruchid species, did not stimulate callus formation. Based on partitioning and TLC analysis, the biologically active constitutent(s) was stable and nonpolar. Thus, theNp allele probably conditions sensitivity to a nonpolar component of pea weevil oviposition as a mechanism of resistance to the weevil. PMID- 24233571 TI - Effect of phase-feeding crude protein on performance and carcass characteristics of crossbred beef bulls: an application to reduce nitrogen compounds in beef cattle diets. AB - Beef cattle (24) with an average initial body weight of 417 +/- 54 kg were assigned in a 2 * 2 factorial design with six repetitions. The factors studied were two levels of CP: 11 (low CP) or 13 % (high CP) in the initial feedlot phase (days 1 - 36) and in the final phase (days 37 - 72). After 36 days, half of the bulls fed with each level of CP were selected to reverse the CP level. No interaction was observed (P > 0.05) between the level of protein in the initial and final phases on the intake of the nutrients evaluated. There was no effect (P > 0.05) of the protein levels in the initial and final phases on intake of dry matter, organic matter, CP, non-fiber carbohydrates, and total digestible nutrients. No differences were observed among treatments (P > 0.05) for average daily gain (X = 1.99 kg/day) and carcass traits. We conclude that it is possible to feed Holstein-Zebu crossed bulls with an average daily gain of approximately 2 kg using a fixed level of 11 % CP during the entire feedlot period, and this diet is economically viable and environmentally sound. PMID- 24233572 TI - Microbiological studies of Tokyo Bay. AB - The generic composition of the heterotrophic bacterial population of Tokyo Bay, which is now highly polluted and eutrophic, was compared with that of the adjacent, less polluted regions of Sagami Bay and Suruga Bay. Members of Vibrionaceae predominated in the bacterial flora of seawater and zooplankton samples from Sagami Bay, Suruga Bay, and the mouth of Tokyo Bay. However,Vibrio spp. formed only a small proportion of the bacterial population of the water and sediment samples from the inner Tokyo Bay; there the Gram-negative, nonmotile, nonpigmented bacteria, which were tentatively identified asAcinetobacter, were predominant. The result of experiments, in which seawater samples from Tokyo Bay were incubated under various experimental conditions, indicated that two significant factors apparently control the growth ofVibrio spp. in seawater; (1) a direct antagonism betweenVibrios and phytoplankton undergoing rapid growth, and (2) a limiting organic nutrient forvibrios. PMID- 24233573 TI - Denitrification in salt marsh sediments: Evidence for seasonal temperature selection among populations of denitrifiers. AB - Direct measurements of bacterial denitrification in salt marsh sediments near Woods Hole, Massachusetts were made over a 10-month period using a simple and precise gas-chromatographic technique. Based on laboratory experiments at 5 degrees , 10 degrees , and 20 degrees C, it is shown that seasonal temperature variations select for at least two distinct populations of denitrifiers.In situ incubations suggest that resident populations of denitrifying bacteria are cold sensitive. Salt marsh denitrifying bacteria are not optimally adapted to their thermal environment, but to temperatures 5 degrees -10 degrees C higher. In these water-logged muds, rates of bacterial denitrification (0.3-1.5MUg N2/gm sediment hr) are up to three orders of magnitude greater than maximum potential rates of insitu bacterial and algal nitrogen fixation. PMID- 24233574 TI - The combined relationship of temperature and molybdenum concentration to nitrogen fixation byAnabaena cylindrica. AB - The joint effects of growth temperature, incubation temperature, and molybdenum concentration on the nitrogen fixation rate ofAnabaena cylindrica were determined using the acetylene-reduction technique. The nitrogen-fixation response to increased molybdenum concentration varied among three growth temperatures (15 degrees , 23 degrees , and 30 degrees C). The pattern of rate change was similar within a growth temperature but increased overall in magnitude with the three incubation temperatures (also 15 degrees , 23 degrees , and 30 degrees C). The maximum rate of nitrogen fixation occurred at 30 degrees C regardless of previous growth temperature. The minimum molybdenum concentration necessary to yield substantial acetylene reduction varied with growth temperature: at 15 degrees C, 15MUg 1(-1) was effective; at 23 degrees C, less than 5MUg 1(-1) was effective; and at 30 degrees C, 50MUg 1(-1) was effective. At all three growth temperatures, increases in molybdenum concentration above the minimum effective concentration produced increases in acetylene reduction. However, at higher molybdenum concentrations inhibition of nitrogen fixation occurred. PMID- 24233575 TI - The breakdown of malathion in soil and soil components. AB - The disappearance of the organophosphorus insecticide, malathion, from a silt loam soil and from its organic and inorganic components was examined. Half-lives and the time taken for 90% decomposition in nonsterile, sodium azide-treated, and 2.5 Mrad-irradiated soils were similar (3/4-1 1/2 days and 4-6 days, respectively) but breakdown in autoclaved soils was negligible. Decay in nonsterile sand, silt, and clay minus organic matter fractions was 3-6 times slower than that recorded in the original soil. Breakdown of malathion in the clay plus organic matter fraction (organo-mineral complex) was rapid (half-life, 1 day), as was the case in the separated organic matter (half-life, 1 3/4 days). Filter-sterilized organic matter was not as effective in catalyzing the breakdown of malathion (half-life, 4 days), and no loss occurred from any of the autoclaved components. Irradiation doses of 2.5 and 5.0 Mrad had little influence on the ability of soil to degrade malathion. Thereafter, increases up to 20 Mrad had a more drastic, though far from totally inhibitory, effect. Our results suggest that either the colloidal organic matter itself, or a fraction associated with it, is the most important single factor concerned with the rapid breakdown of malathion in the soil studied. Direct microbial metabolism is a slower process and may have a significant role in malathion disappearance in coarsetextured soils low in colloidal organic matter. The catalytic component of the organic matter is suggested to be a stable exoenzyme and is supportive of reports by other workers. The quantitative effect of organo-mineral complex (containing the active degradative ingredient) additions to sand and silt fractions on the rate of subsequent malathion decay is also described. PMID- 24233576 TI - Influence of heavy metal leaf contaminants on the in vitro growth of urban-tree phylloplane-fungi. AB - The surfaces of urban woody vegetation are contaminated with varying amounts of numerous metallic compounds, including Cd, Cu, Mn, Al, Cr, Ni, Fe, Pb, Na, and Zn. To examine the possibility that these metals may affect phylloplane fungi, the above cations were tested in vitro for their ability to influence the growth of numerous saprophytic and parasitic fungi isolated from the leaves of London plane trees. Considerable variation in growth inhibition by the metals was observed. GenerallyAureobasidium pullulans, Epicoccum sp., andPhialophora verrucosa were relatively tolerant;Gnomonia platani, Cladsporium sp., andPleurophomella sp. were intermediate; andPestalotiopsis andChaetomium sp. were relatively sensitive to the incorporation of certain metals into solid and liquid media. If similar growth inhibitions occur in nature, competitive abilities or population structures of plant surface microbes may be altered by surface metal contamination. Metals causing the greatest and broadest spectrum growth suppression included Ni, Zn, Pb, Al, Fe, and Mn. PMID- 24233577 TI - Growth of an estuarinePseudomonas sp. on polychlorinated biphenyl. AB - In the course of a study of the microbial degradation of polychlorinated biphenyls (PCB), 16 cultures, representing 5 genera of bacteria, were isolated. APseudomonas sp. was found to degrade mixtures of PCB (Aroclor 1254) and pure isomers, i.e., hexachlorobiphenyl (HCB). Degradation was found to be variable, depending on length of incubation, purity, and degree of chlorination of the biphenyl molecule. In addition to apparent degradation of PCB, it was observed that PCB stimulated growth and oxygen uptake. Bioaccumulation of PCB residues was suggested since(14)-Clabeled material derived from(14)C-PCB accumulated on or in the bacterial cells. The potential degradation and utilization of PCB by microorganisms suggests that this may be an important mechanism for removal or mobilization of PCB into food chains in the estuarine environment. PMID- 24233578 TI - Simulating continuous renal replacement therapy: usefulness of a new simulator device. AB - Simulation allows the training of life-support procedures without patient risk. We analyzed the performance and usefulness of a new device that makes feasible the external control of continuous renal replacement therapy (CRRT) machines in order to realistically generate clinical conditions and problems in simulated patients. A simple mechanical device was designed according to training needs and then hand made. This device permits the control of all monitorable pressures and therefore allows simulation of a range of clinical situations and eventual complications that might occur in real patients. We tested its performance in vitro and then during 16 high-fidelity patient-simulation scenarios included in the program of pediatric CRRT courses. Student and teacher satisfaction was assessed through an anonymous survey. Quick, accurate, real-time monitor of pressure changes, concordant with the usual clinical problems to be simulated (catheter complications, filter coagulation, inadequate CRRT device settings), were easily achieved with the new device. Instructors rated the device as user friendly and well adapted to the reality being simulated. During scenarios, students were not aware of the simulator and considered that simulated clinical conditions were realistic. Our device may be very useful for training healthcare professionals in CRRT management, thus avoiding risk to patients. PMID- 24233579 TI - Effects of dual transcranial direct current stimulation for aphasia in chronic stroke patients. AB - OBJECTIVE: To investigate any additional effect of dual transcranial direct current stimulation (tDCS) compared with single tDCS in chronic stroke patients with aphasia. METHODS: Eleven chronic stroke patients (aged 52.6+/-13.4 years, nine men) with aphasia were enrolled. Single anodal tDCS was applied over the left inferior frontal gyrus (IFG) and a cathodal electrode was placed over the left buccinator muscle. Dual tDCS was applied as follows: 1) anodal tDCS over the left IFG and cathodal tDCS over the left buccinator muscle and 2) cathodal tDCS over the right IFG and anodal tDCS over the right buccinator muscle. Each tDCS was delivered for 30 minutes at a 2-mA intensity. Speech therapy was provided during the last 15 minutes of the tDCS. Before and after the stimulation, the Korean-Boston Naming Test and a verbal fluency test were performed. RESULTS: The dual tDCS produced a significant improvement in the response time for the Korean Boston Naming Test compared with the baseline assessment, with a significant interaction between the time and type of interventions. Both single and dual tDCS produced a significant improvement in the number of correct responses after stimulation with no significant interaction. No significant changes in the verbal fluency test were observed after single or dual tDCS. CONCLUSION: The results conveyed that dual tDCS using anodal tDCS over the left IFG and cathodal tDCS over the right IFG may be more effective than a single anodal tDCS over the left IFG. PMID- 24233580 TI - Age- and cohort-related variance of type-A behavior over 24 years: the Young Finns Study. AB - BACKGROUND: Over the recent decades, the incidence of cardiovascular and heart diseases has decreased while levels of type-A behavior, i.e., a potential risk factor, appear to have increased. However, the long-term developmental patterns of type-A behavior is poorly understood. Both age- and cohort-related changes may be involved in these developments. PURPOSE: The purpose of this study was to examine an age- and cohort-related changes of Hunter-Wolf type-A behavior from adolescence to adulthood. METHODS: Type-A behavior and its components (aggressiveness, leadership, hard driving, and eagerness energy) were assessed using the Hunter-Wolf A-B rating scale at five time points (1983, 1986, 1989, 2001, and 2007) in a population-based sample consisting of six birth cohorts born between 1962 and 1977 (n = 3,341, a total of 10,506 person observations). Development of type-A behavior and its components was examined with cohort sequential multilevel modeling. RESULTS: Aggressiveness decreased with age, eagerness energy, hard driving, and global type-A behavior increased, and leadership exhibited no mean level changes. Younger cohorts had higher aggressiveness, lower hard driving, and global type-A behavior. CONCLUSIONS: The findings suggest that in order to understand the health consequences of type-A behavior, both life span and societal changes should be considered. PMID- 24233581 TI - Guanine-copper coordination polymers: crystal analysis and application as thin film precursors. AB - Three copper-N9-modified guanine complexes are reported with structures ranging from a discrete trinuclear motif to a mixed-valence coordination polymer. These complexes were used as precursors for the deposition and growth of copper oxide thin films on Si(100), at two different annealing temperatures, by using a CVD technique. Subsequent resistivity measurements suggest the formation of conductive thin films, raising the possibility of using nucleobase-metal complexes as versatile thin film precursors. PMID- 24233582 TI - Complete Genome Sequences of Five Paenibacillus larvae Bacteriophages. AB - Paenibacillus larvae is a pathogen of honeybees that causes American foulbrood (AFB). We isolated bacteriophages from soil containing bee debris collected near beehives in Utah. We announce five high-quality complete genome sequences, which represent the first completed genome sequences submitted to GenBank for any P. larvae bacteriophage. PMID- 24233583 TI - Complete Genome Sequence of Staphylococcus aureus Siphovirus Phage JS01. AB - Staphylococcus aureus is the most prevalent and economically significant pathogen causing bovine mastitis. We isolated and characterized one staphylophage from the milk of mastitis-affected cattle and sequenced its genome. Transmission electron microscopy (TEM) observation shows that it belongs to the family Siphovirus. We announce here its complete genome sequence and report major findings from the genomic analysis. PMID- 24233584 TI - Draft Genome Sequence of Lactobacillus fermentum Lf1, an Indian Isolate of Human Gut Origin. AB - Lactobacillus fermentum is a normal inhabitant of the human gastrointestinal tract. Here, we report the draft genome sequence of an Indian isolate of the probiotic strain L. fermentum Lf1, isolated from the human gut. PMID- 24233585 TI - Complete Genome Sequence of Salmonella enterica subsp. enterica Serovar Thompson Strain RM6836. AB - Salmonella enterica subsp. enterica serovar Thompson strain RM6836 was isolated from lettuce in 2002. We report here the complete sequence and annotation of the genome of S. Thompson RM6836. This is the first reported complete genome sequence for S. Thompson and it will enhance our understanding of this serovar and provide another point for comparative studies between Salmonella enterica strains. PMID- 24233586 TI - Genome Sequence of a Circulating Human-Like Swine-Origin Influenza A Virus H3N2 Strain. AB - The full-genome sequence of A/swine/Henan/1/2010, a strain of influenza A virus isolated in central China, was determined. Phylogenetic analyses show that its eight genomic segments are human-like, and some of its segments have appeared in swine H1N2, swine H1N1, and human H1N2 influenza viruses. PMID- 24233587 TI - Complete Genome Sequences of Helicobacter pylori Clarithromycin-Resistant Strains. AB - We report the complete genome sequences of two Helicobacter pylori clarithromycin resistant strains. Clarithromycin (CLR)-resistant strains were obtained under the exposure of H. pylori strain 26695 on agar plates with low clarithromycin concentrations. The genome data provide insights into the genomic changes of H. pylori under selection by clarithromycin in vitro. PMID- 24233588 TI - Draft Genome Sequence of Loktanella cinnabarina LL-001T, Isolated from Deep-Sea Floor Sediment. AB - This report describes the draft genome sequence of Loktanella cinnabarina LL 001(T), which was the first isolated strain from deep-sea floor sediment of the genus Loktanella. The draft genome sequence contains 3,896,245 bp, with a G+C content of 66.7%. PMID- 24233589 TI - Metagenome sequencing of prokaryotic microbiota from two hypersaline ponds of a marine saltern in santa pola, Spain. AB - Marine salterns are composed of several shallow ponds with a salinity gradient, from seawater to salt saturation, with gradually changing microbial populations. Here, we report the metagenome sequencing of the prokaryotic microbiota of two ponds with 13% and 33% salinity from a saltern in Santa Pola, Spain. PMID- 24233590 TI - The Rhizobacterium Bacillus amyloliquefaciens subsp. plantarum NAU-B3 Contains a Large Inversion within the Central Portion of the Genome. AB - The genome of rhizobacterium Bacillus amyloliquefaciens subsp. plantarum strain NAU-B3 is 4,196,170 bp in size and harbors 4,001 genes. Nine giant gene clusters are dedicated to the nonribosomal synthesis of antimicrobial lipopeptides and polyketides. Remarkably, NAU_B3 contains a large inversion within the central portion of the genome. PMID- 24233591 TI - Draft Genome Sequence of Geobacillus thermoleovorans Strain B23. AB - Here, we report the draft genome sequence of Geobacillus thermoleovorans strain B23, which was isolated from a deep subterranean petroleum reservoir in Japan. An array of genes related to unique long-chain alkane degradation pathways in G. thermoleovorans B23 has been identified by whole-genome analyses of this strain. PMID- 24233592 TI - Draft Genome Sequence of a Plant Growth-Promoting Rhizobacterium, Serratia fonticola Strain AU-P3(3). AB - Plant growth-promoting rhizobacteria (PGPR), found in the rhizospheric region of plants, not only suppress plant disease, but also directly improve plant health by improving the availability of nutrients and by providing phytostimulants. Herein, we report the high-quality genome sequence of Serratia fonticola strain AU-P3(3), a PGPR of the pea plant, which confers phosphate solubilization, indole 3-acetic acid production, ammonia production, hydrogen cyanide (HCN) production, and siderophore production and also confers activity against Rhizoctonia species. The 5.02-Mb genome sequence contains genes related to plant growth promotion and biocontrol activities. PMID- 24233593 TI - Draft Genome Sequence of the Arsenate-Respiring Bacterium Chrysiogenes arsenatis Strain DSM 11915. AB - Here we present the draft genome sequence of Chrysiogenes arsenatis strain DSM 11915, only the second genome sequence from the phylum Chrysiogenetes. This strictly anaerobic organism was isolated from arsenic-contaminated gold mine wastewater and respires arsenate or nitrate instead of oxygen. The assembly contains 2,824,977 bp in 22 scaffolds. PMID- 24233594 TI - Draft Genome Sequence of Sphingobium ummariense Strain RL-3, a Hexachlorocyclohexane-Degrading Bacterium. AB - Here, we report the draft genome sequence of the hexachlorocyclohexane (HCH) degrading bacterium Sphingobium ummariense strain RL-3, which was isolated from the HCH dumpsite located in Lucknow, India (27 degrees 00'N and 81 degrees 09'E). The annotated draft genome sequence (4.75 Mb) of strain RL-3 consisted of 139 contigs, 4,645 coding sequences, and 65% G+C content. PMID- 24233595 TI - Third conference on methods and applications of fluorescence spectroscopy, prague, czech republic, october 18-21, 1993. PMID- 24233596 TI - A new concept of photogeneration of cations: Evidence for photoejection of Ca(2+) and Li (+) from complexes with a crown-ether-linked merocyanine by picosecond spectroscopy. AB - Time-resolved transient absorption and gain spectra of DCM-crown and its complexes with Li(+) and Ca(2+) in acetonitrile are measured in the wavelength range 370-670 nm after subpicosecond excitation at 425 nm. The results give evidence for the fast formation of free DCM-crown from both excited complexes, with a faster rate for the Li(+) complex. A two-step mechanism is found for the initial decay (within 30 ps) of the free DCM-crown. PMID- 24233597 TI - Coumarinic fluorescent chemosensors for the detection of transition metal ions. AB - Fluoroionophores consisting of coumarin-153 linked to mono- and diaza-crown ethers are able to complex transition metal cations (Ni(2+), Zn(2+), Cd(2+)) and Pb(2+), with concomitant large changes in photophysical properties. The stability constants in acetonitrile are higher than 3*10(6) M (-1) except for Ni(2+). PMID- 24233598 TI - Fluorescence of metal complexes of 8-hydroxyquinoline derivatives in aqueous micellar media. AB - The fluorescence characteristics of 8-hydroxyquinoline derivative complexes of A1(III), Ga(III), In(III), Zn(II), and Be(II) in differently charged micellar media are reported. For most of the chelates studied, large increases are observed in micellar media compared with those obtained in hydroorganic solvents. However, some exceptions are observed, of which the low fluorescence of Zn(II) chelates in anionic sodium lauryl sulfate media is the most noticeable. PMID- 24233599 TI - Fluorescent nucleoside derivatives: Luminescence study of 4 dimethylaminopyridinium chloride derived from guanosine. AB - Photophysical properties of fluorescentN-[2-amino-9-(2',3',5'-tri-O-acetyl-beta-D ribofuranosyl)-purin-6-yl]-4-dimethylaminopyridinium chloride (GDMAP) are determined in view of its possible use as a probe in DNA. The fluorescence intensity of GDMAP increases and exhibits doubleexponential decay in the presence of common nucleosides. The formation of ground-state complexes with nucleosides is inferred from absorption and emission measurements. PMID- 24233600 TI - DEDO: A specific, fluorescent inhibitor for spectroscopic investigations of Na,K ATPase. AB - The interaction between the fluorescent ouabain derivative DEDO and purified renal Na,K-ATPase (isolated from different animal species) is investigated. Equilibrium binding studies provide a pK value of about 7.5 and a stoichoimetric coefficient of 1. Nonmodified ouabain exhibits the same affinity to the rabbit enzyme; the enzyme originating from the other sources binds DEDO 10 times less strongly than ouabain. Kinetic studies indicate that this is the consequence of a 10 times higher dissociation rate constant of the complexes formed with DEDO. The fluorescence emission intensity of DEDO is enhanced, being dependent on the enzyme source. The single decay time of DEDO is 3 ns in the absence and 21 ns in the presence of the rabbit enzyme and 14 ns in the presence of the pig renal enzyme. This result suggests that the fluorophore of DEDO is bound to a very hydrophobic environment of the enzyme. Further characterization of the static fluorescence spectra provides evidence for energy transfer between Trp residues of the enzyme and DEDO. Distance estimations suggest that one or two Trp residues are likely to be located in the proximity of the fluorophore. PMID- 24233601 TI - Confocal fluorescence lifetime imaging of free calcium in single cells. AB - Ca(2+) concentrations in biological cells are widely studied with fluorescent probes. The probes have a high selectivity for free calcium and exhibit marked changes in their photophysical properties upon binding. The differences in the fluorescent lifetime of the probes can now be used as a contrast mechanism for imaging purposes. This technique can be further exploited for the quantitative determination of ion concentrations within the cells. We describe the use of a fast fluorescence lifetime imaging method in combination with a standard confocal laser scanning microscope for the determination of Ca(2+) concentrations in single rat cardiac myocytes using the intensity probe Calcium Green. PMID- 24233602 TI - Visualization of lipid-receptor interactions on single cells by time-resolved imaging fluorescence microscopy. AB - The physical interaction between plasma-membrane lipids and the epidermal growth factor (EGF)-receptor was investigated on single A431 human epidermoid carcinoma cells by monitoring fluorescence resonance energy transfer (FRET) between exogeneously added fluorescein-EGF (donor) and 2-(4,4-difluoro-5,7-dimethyl-4 bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3 phosphocholine (Bodipy-PC, acceptor) using donor-photobleaching FRET-microscopy. The measured mean FRET-efficiency of 13% is indicative of such a physical interaction and exemplifies the great potential and sensitivity of time-resolved imaging fluorescence microscopy techniques for the study of lipid-receptor interactions on single cells. PMID- 24233603 TI - Characterization of human immunodeficiency virus-1 (HIV-1) rev by (time-resolved) fluorescence spectroscopy. AB - Fluorescence spectroscopy has been applied to the single tryptophan-containing regulatory protein Rev of human immunodeficiency virus (HIV-1). The fluorescence emission was found to have a maximum at 336 nm which refers to a surrounding of the chromophore of intermediate polarity. Fluorescence transients recorded at the maximum of fluorescence were found to decay nonexponentially. A bimodal lifetime distribution is obtained from exponential series analysis (ESM) with centers at 1.7 and 4.5 ns. Two microenvironments for tryptophan are suggested to be responsible for the two lifetime distributions. No innerfilter effect occurred in a Rev solution up to a concentration of 40 MUM. A data quality study of ESM analysis as function of collected counts in the peak channel maximum (CIM) showed that, for reliable reconvolution, at least 15,000 CIM are necessary. The widths of the two distributions are shown to be temperature dependent. The broadening of the lifetime distributions when the temperature is raised to 50 degrees C is interpreted as extension of the number of conformational substates which do not interconvert on the fluorescence time scale. The thermal deactivation (temperature quenching) is reflected in a constant decrease in the center of the short-lived lifetime distribution. PMID- 24233604 TI - Analysis of cell surface molecular distributions and cellular signaling by flow cytometry. AB - Flow cytometry is a fast analysis and separation method for large cell populations, based on collection and processing of optical signals gained on a cell-by-cell basis. These optical signals are scattered light and fluorescence. Owing to its unique potential ofStatistical data analysis and sensitive monitoring of (micro)heterogeneities in large cell populations, flow cytometry-in combination with microscopic imaging techniques-is a powerful tool to study molecular details of cellular signal transduction processes as well. The method also has a widespread clinical application, mostly in analysis of lymphocyte subpopulations for diagnostic (or research) purposes in diseases related to the immune system. A special application of flow cytometry is the mapping of molecular interactions (proximity relationships between membrane proteins) at the cell surface, on a cell-by-cell basis. We developed two approaches to study such questions; both are based ondistance-dependent quenching of excited state fluorophores (donors) by fluorescent or dark (nitroxide radical) acceptors via Forstertype dipole-dipole resonance energy transfer (FRET) and long-range electron transfer (LRET) mechanisms, respectively. A critical evaluation of these methods using donor- or acceptor-conjugated monoclonal antibodies (or their Fab fragments) to select the appropriate cell surface receptor or antigen will be presented in comparison with other approaches for similar purposes. The applicability of FRET and LRET for two-dimensional antigen mapping as well as for detection of conformational changes in extracellular domains of membrane-bound proteins is discussed and illustrated by examples of several lymphoma cell lines. Another special application area of flow cytometry is the analysis of different aspects of cellular signal transduction, e.g., changes of intracellular ion (Ca(2+), H(+), Na(+)) concentrations, regulation of ion channel activities, or more complex physiological responses of cell to external stimuli via correlated fluorescence and scatter signal analysis, on a cell-by-cell basis. This way different signaling events such as changes in membrane permeability, membrane potential, cell size and shape, ion distribution, cell density, chromatin structure, etc., can be easily and quickly monitored over large cell populations with the advantage of revealing microheterogeneities in the cellular responses. Flow cytometry also offers the possibility to follow the kinetics of slow (minute and hour-scale) biological processes in cell populations. These applications are illustrated by the example of complex flow cytometric analysis of signaling in extracellular ATP-triggered apoptosis (programmed cell death) of murine thymic lymphocytes. PMID- 24233605 TI - Study of DNA accessibility in the condensed chromatin structures by resonance energy transfer. AB - The linker DNA accessibility of chicken erythrocyte chromatin was studied by diffusion-enhanced resonance energy transfer (DERET). The 4"-{9'''-[((4-carboxy-3 hydroxyphenyl)-acetatamido)-3''',6''',9'''-(triacetyl)-3",6''',9''' triazanonamido]-2",6"-diazanonyl}-4,5',8-trimethyl psoralen-terbium complex was photocovalently bound to linker DNA and transferred its energy to fluorescein free in solution or bound on proteins of different sizes. We observed a diminution of linker DNA accessibility in chromatin as the protein size increased. Free fluorescein and proteins (up to a molecular weight of 24,000) labeled with fluorescein isothiocyanate (FITC) showed no variation in linker accessibility as chromatin condensation from 10- to 30-nm fibers was induced by an increase in ionic strength. We can conclude from these observations that linker DNA is located on the outside of the condensed chromatin fiber or, alternatively, that small proteins are free to diffuse toward an inside-located linker DNA, even in the condensed state of chromatin, possibly through the central cavity of the solenoid model. PMID- 24233606 TI - Fluorescence labeling and interaction of atherogenic lipoproteins with cultured cells. AB - We prepared lipoprotein (a) and LDL covalently labeled with either BODIPY or rhodamine. A dual wavelength method was used for the microscopic observation of both lipoproteins during their interaction with HepG2 cells. Since a large proportion of Lp(a) colocalized with LDL on the cell surface and inside the cells, it was concluded that Lp(a) uptake into cells is mediated by LDL via internalization of LDL. PMID- 24233607 TI - Application of angle-resolved fluorescence depolarization in muscle research. AB - Angle-resolved fluorescence depolarization (AFD) experiments have been used for over a decade in studies of fluorescent molecules in macroscopically aligned systems such as lipid bilayers and stretched polymer films. The importance of this technique lies in the fact that it affords the determination of both the second- and the fourth-rank order parameters of the orientational distribution of the probe molecules in the sample. Here we apply the technique to the study of the orientational distribution of crossbridges in muscle fibers. This orientational distribution is particularly relevant in muscle research, as crossbridge rotation is commonly regarded to be the driving mechanism in force development. An unfortunate consequence of the fact that the crossbridges have an average orientation of approximately 45(o) relative to the fiber axis is that the values of the second-rank order parameter [Symbol: see text]P 2[Symbol: see text] of the crossbridge distribution are close to 0. Therefore, knowledge of [Symbol: see text]P 4[Symbol: see text] is essential for a reliable reconstruction of the form of the distribution function. AFD of dyelabeled muscle was measured under rigor and relaxation conditions. The results indicate that no significant changes in depolarization take place upon a transition from the rigor to the relaxed state in the muscle and seem not to support the rotating crossbridge model, which postulates a clear change of orientation of the crossbridges. PMID- 24233608 TI - Static and dynamic quenching of luminescent species in polymer media. AB - A method developed for quantitative determination of static and dynamic contributions to luminescence quenching is applied to Ru(II) complexes in polymer matrices (silica gel and polystyrene), quenched by oxygen. This method is based on both intensity and lifetime quenching experiments. The curvature of intensity Stern-Volmer plots is related to the results. PMID- 24233609 TI - Fluorescence intensity and anisotropy decays of the DNA stain Hoechst 33342 resulting from one-photon and two-photon excitation. AB - We examined the steady-state and time-resolved fluorescence spectral properties of the DNA stain Hoechst 33342 for one-photon (OPE) and two-photon (TPE) excitation. Hoechst 33342 was found to display a large cross section for two photon excitation within the fundamental wavelength range of pyridine 2 and rhodamine 6G dye lasers, 690 to 770 and 560 to 630 nm, respectively. The time resolved measurements show that intensity decays are similar for OPE- and TPE. The anisotropy decay measurements of Hoechst 33342 in ethanol revealed the same correlation times for TPE as observed for OPE. However, the zero-time anisotropies recovered from anisotropy decay measurements are 1.4-fold higher for TPE than for OPE. The anisotropy spectra of Hoechst 33342 were examined in glycerol at -20 degrees C, revealing limiting values close to the theoretical limits for OPE (0.4) and TPE (0.57). The steady-state anisotropy for OPE decreases in the shorter-wavelength region (R6G dye laser, 280-315 nm), but the two-photon anisotropy for 560 to 630-nm excitation remains as high as in the long wavelength region (690-770 nm). This result suggests that one-photon absorption is due to two electronic, but only one transition contributes to the two-photon absorption over the wavelength range from 580 to 770 nm. Our demonstration of these favorable two-photon properties for Hoechst 33342, and the high photostability of the dye reported by other laboratories, suggests that this dye will be valuable for time-resolved studies of DNA with TPE and for two-photon fluorescence microscopy. PMID- 24233610 TI - On the use of tryptophan to detect slow orientational motions. AB - For our investigations on orientational motions of membrane proteins with the method of time-resolved fluorescence anisotropy decay (TRFA), we first wanted to test the use of tryptophan fluorescence in detecting slow motions on the time scale of tens of nanoseconds and to get more insight into the possible motions of membrane proteins by investigating a simple system. We performed TRFA measurements on a short alpha-helical 21-amino acid peptide in different environments (Vogel, H.,et al. Proc. Natl. Acad. Sci. USA 85, 5067-5071, 1988). In each case, we got three relexation time constants. The longest of these depends strongly on changes in the environment, whereas the two shorter times show only weak dependencies. So we conclude that the longest time belongs to the rotational diffusion of the entire peptide and the other to internal motions. PMID- 24233611 TI - Surface area per molecule in lipid/C12E n membranes as seen by fluorescence resonance energy transfer. AB - Fluorescence resonance energy transfer (FRET) from NBD-PE to rhodamine-PE has been used to measure the average area occupied by surfactant molecules in lipid bilayers. The Foerster radius has been determined from the spectral overlap of donor fluorescence and acceptor absorption (R 0=4.6 nm). The results of steady state as well as of time-resolved investigations have been compared. The analysis of time-resolved fluorescence data by means of nonexponential decay functions yields an average area per lipid of 0.65 nm(2) in pure POPC bilayers. The area per surfactant in two-component C12E n /POPC-membranes (n=2, 4, 6) has been determined and compared with the results of X-ray investigations. The surfactant head group seems to adapt a predominantly disordered confirmation within the bilayer. PMID- 24233612 TI - Measurement of the binding of DNA to liposomes by resonance energy transfer. AB - A rapid and simple semiquantitative method for monitoring the attachment of DNA to liposomes is described. This technique is based on the measurement of resonance energy transfer between a membrane-embedded fluorescent pyrene lipid donor and DNA labeled with adriamycin as an acceptor. PMID- 24233613 TI - Determination of the partition coefficients of the nonionic detergent C12E 7 between lipid-detergent mixed membranes and water by means of Laurdan fluorescence spectroscopy. AB - The membrane-water partition coefficient of the detergent C12E7 between water and C12E7/POPC mixed membranes has been determined by means of steady-state fluorescence spectroscopy. The emission spectra of the fluorescent probe Laurdan were used as an indicator of membrane composition at different membrane concentrations in the sample. The partition coefficient expressed as the ratio of the mole fractions of the detergent in the membrane and water phases is about 6(*)10(5) at low molar ratios of C12E7/POPC (R c ) and decreases rapidly with increasingR c . The limiting detergent content of the lamellar phase (R c (*) >~0.8) is indicated by a minimum ofP(R c ). PMID- 24233614 TI - Time-resolved fluorescence anisotropy measurements on fluorescently tagged amphiphilic micelles. AB - Block copolymers of polystyrene-block-poly)methacrylic acid) form multimolecular micelles in mixtures of 1,4-dioxane with a surplus of methanol at ambient temperatures. Micelles consist of compact polystyrene cores surrounded by outer shells formed by poly(methacrylic acid) and are in a reversible equilibrium with nonmicellized copolymer chains (unimers). A series of light scattering, ultracentrifugation, and fluorimetric measurements was performed on micellizing systems of end-tagged copolymers. Complex time-resolved fluorescence anisotropy decays may be explained by a distribution of fluorophores in two microenvironments, i.e., in compact polystyrene micellar cores and in unimer coils. PMID- 24233615 TI - Study of plasma membrane heterogeneity using a phosphatidylcholine derivative of 1,6-diphenyl-1,3,5-hexatriene [2-(3-(diphenylhexatriene)propanoyl)-3-palmitoyl-L alpha-phosphatidylcholine]. AB - The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) and DPH derivatives have been used to characterize structural and physicochemical properties of specific membrane domains. Steady-state and fluorescence decay measurements of three probes, DPH (1,6-diphenyl-1,3,5-hexatriene), TMA-DPH [1-(4-trimethyl ammonium-phenyl)-6-phenyl-1,3,5-hexatriene], and a phosphatidylcholine derivative of DPH, DPH-pPC [2-(3-(diphenylhexatriene)propanoyl)-3-pamitoyl-L-alpha phosphatidyl choline], have been performed in erythrocyte membranes and in lymphocyte plasma membranes. The steady-state fluorescence polarization of the three probes showed a similar trend in both membranes. In fact either in erythrocyte or in lymphocyte plasma membranes the fluorescence polarization values of DPH-pPC and TMA-DPH were similar, but significantly higher with respect to DPH. A better characterization of erythrocyte and lymphocyte plasma membranes was possible by using fluorescence decay measurements. The data suggest the possible use of different DPH derivatives to characterize specific domains in biological membranes. PMID- 24233616 TI - Diphenylhexatriene-phosphatidylcholine fluorescence in POPC vesicles: Comparison of the exponential-series and the maximum-entropy methods. AB - We have investigated the time-resolved fluorescence of diphenylhexatriene (DPH) covalently linked to phosphatidylcholine (PC) in palmitoyloleoylglycerophosphocholine (POPC) vesicles with special consideration of the comparison of two methods for distributional lifetime analysis: the exponential-series method (ESM) and the maximum-entropy method (MEM). Generally, both methods were found to reveal equivalent results on high-quality data. Different are the shapes of the recovered distributions (symmetry and width) as well as the time effort for the numerical analysis. PMID- 24233617 TI - Conformational effects on the fluorescence of pyrene-labeled alkyldiacyl glycerols in different model membranes. AB - We synthesized two isomeric alkyldiacyl glycerols containing pyrene as a fluorescent reporter group bound to the omega end of both acyl chains. If located in the phospholipid monolayer of a vesicle both isomers showed intramolecular pyrene excimer fluorescence, indicating parallel orientation of both pyreneacyl chains in the lipid molecule. In micelles only pyrene monomer fluorescence was observed. Thus, in this system the labeled lipids adopt a conformation with both pyreneacyl chains extending into different directions. Using vesicles, lipase activities could be continuously determined from the increase of pyrene monomer fluorescence. PMID- 24233618 TI - Transfer of pyrene-dietherphosphatidylcholine to serum lipoproteins. AB - The nonhydrolyzable fluorescent diether analog of phosphatidylcholine, 1-O hexadecyl-2-0-pyrenedecyl-sn-glycero-3-phosphocholine, has been synthesized as a stable probe for the determination of phospholipid transfer to different lipoprotein classes with potential phospholipase activities. After incubation of total human serum with the new probe at 37 degrees C for 3 hours a characteristic partition equilibrium between the main lipoprotein fractions was observed. The fluorescent lipid was not degraded under these conditions and, therefore, served as a marker for choline glycerophospholipid distribution between and transport to serum lipoproteins. PMID- 24233619 TI - Lateral mobility of plasma membrane proteins in dividing eggs of the loach (Misgurnus fossilis): Regional differences and changes during the cell cycle. AB - Regional differences in lateral diffusion rates of fluorescence-labeled proteins have been studied in the plasma membrane of dividing eggs of the loach (Misgurnus fossilis) by fluorescence recovery after photobleaching (FRAP). Apparent animal vegetal differences in fluorescence intensity, lateral diffusion coefficients, and fractions of mobile proteins have been found, with all these quantities being higher in the animal pole region than in the yolk region. Cyclic changes in protein diffusion coefficients and mobile fractions during the first few cell cycles have also been recorded. Soon after the end of a cleavage, the diffusion coefficient reaches its minimal value and increases rapidly before the next cleavage. PMID- 24233620 TI - Characterization of dimyristoylphosphatidylcholine liposome aggregates induced by dextran sulfate and La(3+) by fluorescence spectroscopy. AB - The addition of dextran sulfate (DS) to DMPC vesicles in the presence of di- and trivalent cations leads to a strong aggregation, resulting in a stack-like arrangement of the opposing membrane surfaces as shown by freeze-fracture electron microscopy. The strong aggregation is connected with a lipid mixing process, especially in the presence of La(3+) (measured by the NBD/Rh assay). The extent of lipid mixing depends on the molecular weight of DS and size of the DMPC vesicles. Additionally, a decrease in the surface dielectric constant of DMPC vesicles [measured by the emission shift of the fluorescent probe, dansylphosphatidyl-ethanolamine (DPE)] was observed. A direct dependence on the molecular weight (MW) of DS exists: the higher their MW, the higher the blue emission shift of the DPE probe. The results are discussed in terms of the theory proposed by Ohki and Arnold, which connects the decrease of the surface dielectric constant with the interaction parameters of phospholipid membranes. PMID- 24233621 TI - Fluorescence methods to study lipid-protein association: The interaction of protein kinase C with lipid-loaded mixed micelles. AB - The interaction of protein kinase C with lipids was studied in a mixed micellar system. Two fluorescence spectroscopic methods are presented with a different but complementary information content. Diffusion monitored by fluorescence correlation spectroscopy provides information on the interaction of the protein with the whole lipid aggregate. Resonance energy transfer from tryptophans to pyrene-labeled lipids monitored by time-correlated single-photon counting supplies information on the interaction of the protein with specific lipid cofactors within the micelle. The results can be extended to postulate new mechanisms for the activation of protein kinase C by the signal transduction cascades in the cell. Both fluorescence spectroscopic methods can be easily applied to other protein systems which interact with lipids. PMID- 24233622 TI - Errata. PMID- 24233623 TI - Gifts, talents, and the dyslexias: Wellsprings, springboards, and finding Foley's Rocks. AB - This presentation draws together findings from the literature on giftedness, on diversity of talents, on definitions and descriptions of intelligence, on the role of emotion in learning, and on the markers and manifestations of the dyslexias. In many instances, high potential in the three-dimensional realm coexists with difficulty in the two-dimensional symbolic or abstract realm. This seeming paradox deserves exploration so educators, parents, and other concerned adults can recognize and nurture students' talents as well as offer appropriate remedial support. PMID- 24233625 TI - Here's to the future. AB - In the near future the thoughtful and creative use of technology can, and should, greatly improve the quality of the curriculum for dyslexic students. The quality of their learning should also be enhanced, provided that educators are fully aware of student needs, have advance training, and have sufficient time and expertise to select and evaluate appropriate software programs.Computers and other multi-media devices must not only be present in the classrooms of the future, but should be fully integrated into the regular instructional system to meet the individual needs of dyslexic students. There should be prior knowledge on the teacher's part of types of software which will lead to curriculum congruence and the achieving of goals unreached without the help of technology.Technology should not be restricted to one content area or discipline, but should be available whenever it can be seen to make learning more profitable and more efficient. Both students and teachers must be granted the freedom to use technology in ways that will encourage creativity, critical thinking, and easy access to information in keeping with intellectual potential. Teacher training and involvement are crucial to the successful use of multi-media in the remediation of skills and extension of knowledge for dyslexic students. PMID- 24233624 TI - The testosterone hypothesis: Assessment since Geschwind and Behan, 1982. AB - The Geschwind hypothesis proposes a causal interaction among non-right handedness, immune disorders, and learning disabilities, including dyslexia, via the intrauterine action of the male hormone testosterone. Some epidemiologic studies have supported at least a statistical association among the three traits; others have not. The associations between learning disorders and immune disease and between learning disorders and non-righthandedness appear to be better supported than that between immune disorders and non-right-handedness. However, none of data thus far accumulated are conclusive because it is not clear that the samples studied have been truly representative.The neuropathologic evidence, both in autopsy studies in human dyslexics and in animal models of developmental cortical abnormalities, are consistent with but not diagnostic of immunological pathology. Mechanisms are discussed by which an abnormal immune system could thus injure the developing brain, with an emphasis placed on abnormal maternal-fetal interactions, including maternal autoimmune disease and maternal-fetal incompatibility. A genetic origin is also possible in which the maternal role is less significant. PMID- 24233626 TI - Whole Language vs. Code Emphasis: Underlying assumptions and their implications for reading instruction. AB - Promoters of Whole Language hew to the belief that learning to read and write can be as natural and effortless as learning to perceive and produce speech. From this it follows that there is no special key to reading and writing, no explicit principle to be taught that, once learned, makes the written language transparent to a child who can speak. Lacking such a principle, Whole Language falls back on a method that encourages children to get from print just enough information to provide a basis for guessing at the gist. A very different method, called Code Emphasis, presupposes that learning the spoken language is, indeed, perfectly natural and seemingly effortless, but only because speech is managed, as reading and writing are not, by a biological specialization that automatically spells or parses all the words the child commands. Hence, a child normally learns to use words without ever becoming explicitly aware that each one is formed by the consonants and vowels that an alphabet represents. Yet it is exactly this awareness that must be taught if the child is to grasp the alphabetic principle and so understand how the artifacts of an alphabet transcribe the natural units of language. There is evidene that preliterate children do not, in fact, have much of this awareness; that the amount they do have predicts their reading achievement; that the awareness can be taught; and that the relative difficulty of learning it that some childen have may be a reflection of a weakness in the phonological component of their natural capacity for language. PMID- 24233627 TI - A success story: A large urban district offers a working model for implementing multisensory teaching into the resource and regular classroom. AB - A large urban school district contracted with a private nonprofit educational foundation to train 126 special education resource teachers in the last three years in an Orton-Gillingham-based program. These teachers are currently teaching learning-disabled students in groups of 8-10 at the elementary level and 10-13 students at the secondary level. Learning-disabled students who qualify for Special Education, either in reading or spelling, or both, are receiving the instruction.The teachers took a Basic Introductory Class (90 hours of Advanced Academic Credit offered by the Texas Education Agency, or six hours of graduate credit at a local university) in order to teach the program in the resource setting. A two year Advanced Training included annual on-site observations, two half-day workshops each fall and spring, and a two-day advanced workshop in the second summer.First grade teachers, one selected from each of the 164 campuses, supervisors, and principals attended a 25-hour course on "Recognizing Dyslexia: Using Multisensory Teaching and Discovery Techniques." The first grade teachers and special education resource teachers collaborated to provide inservice training for their colleagues.Research, conducted by the district's Research Department, reveals statistically significant gains in reading and spelling ability for the learning-disabled resource students as measured by the Woodcock Reading Mastery Test-Revised, and the Test of Written Spelling. PMID- 24233628 TI - Systematic botany: Science to develop language facility. AB - Classification is a fundamental skill that impacts on our abilities to read and to write text. The structure and sequence inherent in the science of taxonomy can be used as the basis for instruction in reading comprehension and in writing. The use of concrete, readily manipulated materials enhances vocabulary development by allowing the teacher to label objects and processes as the student experiences them. There are numerous activities which can be employed to enrich experiential learning; these can be directly related to reading and writing exercises. Processes learned with simple materials can be generalized to more abstract content as the students' proficiency improves. The instructor can control the level of difficulty of the class by writing or selecting materials appropriate to the skills levels of the students involved. Language facility is developed as students progress from the known to the less well known in a series of carefully constructed steps. PMID- 24233629 TI - Dyslexia and psychodynamics: A case study of a dyslexic adult. AB - The interaction between dyslexia and its secondary emotional problems, especially those arising from unproductive defenses, is illustrated in the history and successful treatment of an adult dyslexic male. At the start of treatment, the 33 year-old subject was illiterate, despite an average IQ and a history of many previous educational and therapeutic interventions. Psychological problems, including low self-esteem, alcohol abuse, temper outbursts, and poor relationships with women were seen as largely secondary to the subject's learning problem. A review of the treatment, consisting of remediation concurrent with psychodynamic psychotherapy, reveals specific ways in which these emotional problems hindered educational efforts, as well as ways in which their exploration and resolution in psychotherapy helped the remediation. Similarly, ways in which the subject's learning problem contributed to the development of his emotional problems are discussed. Finally, with reference to the psychoanalytic concept of sublimation, the relationship between improvement in the subject's reading skill and improvement in his impulse control is described. PMID- 24233630 TI - Extrinsic and intrinsic factors in graduation and academic failure among LD college students. AB - A group of 110 LD college students were compared to a random stratified sample (RSS) of 153 peers attending the same moderately selective college between 1980 and 1988. The LD students received comprehensive, highly coordinated support services for at least one semester. The groups were matched on gender, college experience, semester, and year of entry to the college. The LD and RSS groups were compared on high school preparation and performance, ACT and college performance, and graduation and academic failure rate. Although the LD students' high school records, ACT scores, and college performance were inferior to that of the RSS group, they graduated at the same rate and within the same time frame. Neither was there any significant difference in the academic failure rate. Closer examination of the LD graduates and academic failures' performance showed that in spite of the similarities in intellectual abilities, academic achievement, and aptitude-achievement discrepancy, two factors differentiated between the LD graduates and non-graduates: oral language abilities and motivation and attitude toward the teaching-learning process. These two factors accounted for 60 percent of the variance in graduation status. PMID- 24233631 TI - Spelling errors of normal and disabled students on achievement levels one through four: Instructional implications. AB - The errors of 72 disabled and 90 normal spellers were compared on the first through fourth levels of achievement using a featural system based on developmental spelling research. The mean age of the disabled subjects was two to three years higher on all levels (the differences were significant) but, of 24 error features on the four levels, F-tests showed that the groups differed only on Front Vowels (/a/, /e/, /i/), particularly the combination of in as in chin, with the normal group making more errors. Discriminant function analysis showed that the error features which significantly discriminated between the two groups at Level 1 were Consonant Digraphs, Affricates, and Front Vowels. On Level 2, the dominant variables contributing to the significant discriminant function were Front Vowels, consonant doubling and "e-drop" errors, and suffix errors. The normal group made more errors on all but the last. There were no significant differences on Levels 3 and 4. Discriminant analysis among the four levels for the normal group showed that the incidence of lower-level spelling features declined steadily as spelling achievement level increased. A similar trend but less significant variability was found among the disabled group levels. These results suggest that the strict phonetics-based instruction used with the disabled group contributes to their relative proficiency on the lower level spelling features but that the meaning, orthographic, and derivational conventions of more advanced spelling should be emphasized when designing instruction at achievement Level 2 and above. PMID- 24233632 TI - Prediction of dyslexia in kindergarten boys. AB - This study followed 163 boys from kindergarten through fourth grade. A battery of neurospychological and preacademic tests and electrophysiological measures (BEAM) were administered in kindergarten, and reading tests at grade 4, in an attempt to delineate precursors of dyslexia. Three of the kindergarten tasks (giving sounds associated with letters, rapid naming of numbers, and finger localization) differentiated dyslexics from normal readers with 98 percent correct classification. The tasks primarily involve grapheme-phoneme associations, storage and retrieval of phonological information in long-term memory, and verbal labeling. Results are interpreted as confirming the role played by phonological processing tasks in the prediction of dyslexia. Preliminary BEAM results for visual evoked potential topography suggest a significant increment in the distribution of this potential in the left parietal and frontal region, and, for auditory evoked potential topography, a significant difference between the two groups in the right posterior hemisphere. PMID- 24233633 TI - Fine-grained auditory discrimination and performance on tests of receptive vocabulary and receptive language. AB - This research investigated the relation between children's performance on two measures of receptive language and children's auditory discrimination of consonant-vowel sounds having frequency and temporal acoustic differences. The measures of fine-grained auditory discrimination produced significant multiple regression coefficients against both receptive vocabulary (Peabody Picture Vocabulary Test-Revised) and receptive language (Token Test for Children) scores. Validation analyses conducted by predicting receptive vocabulary and language scores for a new sample of children and relating them to the actual scores led to significant outcomes. It was concluded that fine-grained auditory discrimination is particularly important in the relatively early stages of language learning. PMID- 24233634 TI - An examination of familial resemblance among subgroups of dyslexics. AB - The goal of the present study was to ascertain whether developmental dyslexics and their affected parents evinced similar patterns of deficits in word recognition skills. Forty dyslexic children and both their biological parents were administered a battery of experimental measures of phonological and orthographic processing. Deficits in component skills were defined in terms of deviations from the performance of normal readers matched on reading achievement level. Four distinct patterns of deficits were found among both the dyslexics and their parents: a subgroup with a specific deficit in processing phonological codes; a subgroup with a specific deficit in processing orthographic codes; a subgroup with deficits in processing both phonological and orthographic codes; and a subgroup of individuals who did not significantly differ from normal readers at the same reading level in either processing domain. Although limited evidence for familial subgroup concordance was obtained in both the phonological and combined phonological subgroups, no concordance was observed among families classified into the orthographic or reading-achievement equivalent subgroups. It was concluded that all affected family members shared a propensity for a phonological deficit, and that some family members share a fundamental problem in processing orthographic information as well. PMID- 24233635 TI - The effect of systematic training in elaboration on word meaning and prose comprehension in poor readers. AB - This paper reports two interrelated, exploratory training studies to promote word knowledge and textual comprehension through elaboration in poor readers compared with their controls. The results suggest that systematic, sustained in situ training helped these poor readers, although both the training approaches and stimulus materials would need refinement. PMID- 24233637 TI - Foreword. PMID- 24233636 TI - Gender differences in cognitive abilities of reading-disabled twins. AB - Gender differences were assessed in three research-identified samples of children who were members of twin pairs: (1) 120 male and 124 female probands from same sex identical and fraternal twin pairs in which at least one member of each pair is reading disabled; (2) a comparison sample of 148 males and 161 females from same-sex twin pairs with no history of reading problems; and (3) 34 pairs of opposite-sex fraternal twin pairs in which at least one member of each pair is reading disabled. Results of multivariate analyses of variance of psychometric test data from the two samples of same-sex twin pairs, in which the male and female subjects were reared in different homes, suggest that profiles of gender differences are similar in reading-disabled and control children. Moreover, this pattern of gender differences also tended to occur in opposite-sex twin pairs, who shared prenatal, as well as early postnatal, environmental influences. In general, reading-disabled males obtained higher average scores than affected females on Wechsler (1974, 1981) Verbal and Performance IQ, but lower scores on Reading Recognition and Spelling subtests of the Peabody Individual Achievement Test (Dunn and Markwardt 1970). With regard to the Wechsler subtests, reading disabled males achieved higher average scores on Information, Picture Completion, Block Design, and Object Assembly, but lower scores on Coding. Although significant and relatively consistent gender differences in cognitive measures were found in three samples included in this study, these differences account for only a small portion of the observed variance. PMID- 24233640 TI - Analyzing distances in a frontal plane. AB - In an exploration of the process whereby horizontal and vertical components are extracted from distances between pairs of points, participants made speeded absolute distance judgments-deciding whether horizontal distances between pairs of points in a frontal plane exceeded a criterion distance. Judgments reflected the horizontal and vertical distances between the points. Three accounts of the results were considered. (1) Only the overall distance between two points was directly available to judgment processes; the horizontal or vertical distance between the points was available only to the extent that the horizontal and vertical positions of the points were differentially weighted prior to the assessment of overall distance. (2) The perceptual effects of positions on the horizontal and vertical dimensions were collapsed onto a composite dimension. (3) The decision criterion for the distance judgment considered both the horizontal and vertical distances between the points. In support of the overall distance account, (1) performance in the distance judgment task was facilitated by repetition of the same overall distance from trial to trial, but not by repetition of the distance on the composite dimension or by repetition of horizontal or vertical distance; (2) differential weighting that the overall distance account predicted for the absolute distance judgments was reflected in concurrent relative distance judgments pitting horizontal against vertical distance, counter to the composite dimension account, which sees the horizontal and vertical dimensions as collapsing onto the composite dimension in balanced, symmetrical fashion, and counter the decisional account, given that no criterion is required for the relative judgment. PMID- 24233641 TI - Crossmodal interactions in the perception of expressivity in musical performance. AB - In musical performance, bodily gestures play an important role in communicating expressive intentions to audiences. Although previous studies have demonstrated that visual information can have an effect on the perceived expressivity of musical performances, the investigation of audiovisual interactions has been held back by the technical difficulties associated with the generation of controlled, mismatching stimuli.With the present study, we aimed to address this issue by utilizing a novel method in order to generate controlled, balanced stimuli that comprised both matching and mismatching bimodal combinations of different expressive intentions. The aim of Experiment 1 was to investigate the relative contributions of auditory and visual kinematic cues in the perceived expressivity of piano performances, and in Experiment 2 we explored possible crossmodal interactions in the perception of auditory and visual expressivity. The results revealed that although both auditory and visual kinematic cues contribute significantly to the perception of overall expressivity, the effect of visual kinematic cues appears to be somewhat stronger. These results also provide preliminary evidence of crossmodal interactions in the perception of auditory and visual expressivity. In certain performance conditions, visual cues had an effect on the ratings of auditory expressivity, and auditory cues had a small effect on the ratings of visual expressivity. PMID- 24233638 TI - Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. AB - Triple-negative breast cancer (TNBC) is a particular type of breast cancer which is characterized by its biological aggressiveness, worse prognosis, and lack of prognostic markers or therapeutic targets in contrast with hormonal receptor positive and human epidermal growth factor receptor 2-positive (HER2+) breast cancers. We aimed to evaluate survivin and epidermal growth factor receptor (EGFR) expression and their prognostic value and determine their relationships with the clinicopathological parameters of TNBC. A total of 136 patients who had undergone a resection of primary TNBC were enrolled at the Third Affiliated Hospital of Harbin Medical University from March 2003 to September 2005. Expression of ER, PR, HER2, EGFR, and survivin was assessed by immunohistochemistry. The association of TNBC and other clinicopathological variables and the prognostic value of survivin and EGFR expression were evaluated. Survivin was expressed in 62 (45.6 %) cases and EGFR was expressed in 82 (60.3 %) cases. Survivin expression was associated with menopausal status (P = 0.011), tumor size (P = 0.037), and lymph node status (P = 0.001). EGFR expression was associated with menopausal status (P = 0.029), lymph node status (P = 0.004), P53 expression (P = 0.001), Ki-67 expression (P = 0.028), and lymphatic vascular invasion (P = 0.037). A multivariate analysis demonstrated that tumor size (hazard ratio (HR) 1.587, 95 % confidence interval (CI) 1.081 2.330, P = 0.018 for disease-free survival (DFS); HR 1.606, 95%CI 1.096-2.354, P = 0.015 for overall survival (OS)), lymph node status (HR 2.873, 95%CI 1.544 5.344, P = 0.001 for DFS; HR 2.915, 95%CI 1.553-5.471, P = 0.001 for OS), tumor grade (HR 1.914, 95%CI 1.218-3.007, P = 0.005 for DFS; HR 1.983, 95%CI 1.228 3.203, P = 0.005 for OS), EGFR (HR 3.008, 95%CI 1.331-6.792, P = 0.008 for DFS; HR 3.151, 95%CI 1.374-7.226, P = 0.007 for OS), and survivin (HR 1.573, 95%CI 1.087-2.277, P = 0.016 for DFS; HR 1.607, 95%CI 1.088-2.374, P = 0.017 for OS) were of prognostic significance for disease-free and overall survival. We draw a conclusion from the present study that survivin and EGFR expression are useful prognostic markers of TNBC and might be useful for molecular targeting therapy of TNBC treatment. PMID- 24233642 TI - Auditing the precision and accuracy of environmental impact predictions in Australia. AB - Our understanding of natural ecosystems can be measured by our ability to predict their responses to external disturbances. Predictions made during environmental impact assessment (EIA) for major development projects are hypotheses about such responses, which can be tested with data collected in environmental monitoring programmes. The systematic comparison of predicted and actual impacts has been termed environmental impact audit. Ecosystem disturbances associated with major resource developments, though of lesser magnitude than those associated with natural cataclysms, are generally of far greater magnitude than those which can be applied experimentally. Environmental audit can hence provide critical tests of theory in a number of natural sciences. It is also needed to improve the scientific content of EIA. Audits of 4 and 29 EISs respectively have been carried out previously in the UK and USA, but this is the first national scale audit for any country. It is also the first attempt to select, from the many vague statements in EISs, only those predictions that are scientifically testable, and to determine and analyse their quantitative accuracies. Its principal results are as follows. The average accuracy of quantified, critical, testable predictions in environmental impact statements in Australia to date is 44%+/-5% s.e. Predictions where actual impacts proved more than expected were on average significantly (p<0.05) less accurate (33%+/-9%) than those where they proved as or less severe (53%+/-6%). PMID- 24233643 TI - Analyzing censored environmental data using survival analysis: Single sample techniques. AB - The occurrence of censored data due to less than detectable measurements is a common problem with environmental data. The methods of survival analysis, although designed primarily for right censored data and time measured variables, can be adapted to apply censored environmental data. These methods have several theoretical and practical advantages over many existing techniques for dealing with less than detectable measurements. PMID- 24233644 TI - Assessment and prediction of the impacts of the Ok Tedi copper mine on fish catches in the Fly River system, Papua New Guinea. AB - The Ok Tedi copper mine discharges overburden and ore residues into the Ok Tedi, a tributary of the Fly River. These discharges result in elevated suspended solids and dissolved and particulate associated copper. Analyses of covariance were performed to establish statistical model of the relationships between the mine discharges and fish catches between 1983 and 1988. These models were then extrapolated to predict the affects of future mine discharges on fish catches. The models predicted that if the observed effects were caused by particulate associated copper, the period of greatest impact will be between 1989 and 1993, following which catches should be close to 1988 levels for the remainder of mine life. Some additional catches not included in the data set used to derive the models were found to fit the model predictions well. As the predicted period of greatest impact is short and most species reproduce away from the river channel, the ability of the fish communities to undergo partial recovery after 1991 should be maintained. PMID- 24233645 TI - Temporal variability of the elemental composition in urban street dust. AB - Urban Street dust is recognized as a source of urban air and runoff degradation. This paper takes a preliminary step toward a better understanding of temporal variability in street dust chemistry and of the controlling mechanisms. Street dust samples, collected over four seasons in the city of Hamilton, Canada, show a variability dependent on element and source-anthropogenic sources exhibiting the greatest temporal variability. In addition, elements attributed to common sources exhibit similar temporal patterns. The use of 'generic' or even one-time samples may seriously misrepresent the elemental make-up of urban street dust. Based on the samples collected in this study, a number of questions/insights are posed to further the study of street dust temporal variability. PMID- 24233647 TI - Impact studies, cost-benefit analysis and casinos. AB - The simplest forms of impact analysis treat a prospective casino facility as an entirely new source of demand in a region, while completely ignoring the character of supply responses. Such approaches cannot be used to estimate the net benefits of a casino. On the demand side they fail to consider the displacement of other local goods and services, while on the supply side they ignore the fact that most workers have real opportunity costs in the form of alternative employments either inside or outside the region. While various studies have attempted to address the displacement issue, virtually none have looked seriously at the opportunity cost of labor. Evidence suggests that such costs are large. An estimate presented here for Chicago sets these costs at 45% of casino and related labor income. PMID- 24233648 TI - Prevalence of pathological gambling and associated problems in individuals who visit non-gambling video arcades. AB - The objective of the present study was to investigate the gambling behavior of individuals who frequent non-gambling video games arcades. One hundred and twenty two subjects (mean age of 19.2 years (SD=5.5); males constituted 82.8%) who spend time in arcades completed the South Oaks Gambling Screen and the Jacob's Health Survey. The results showed that 10.7% were identified as probable pathological gamblers and 14.8% were problem gamblers. The frequency of visits to arcades for non-gambling activities appeared to be correlated with the extent to which individuals gamble, and is furthermore associated with pathological gambling. The rate of pathological gamblers who frequent arcades is more than twice as high as the rates reported in other studies with adolescents and adults. PMID- 24233649 TI - The phenomenology of 'bad beats': Some clinical observations. PMID- 24233650 TI - The Last Resort revisited: A comment on changes in America. PMID- 24233652 TI - Editors' note. PMID- 24233653 TI - Denitrification and removal of heavy metals from waste water by immobilized microorganisms. AB - Pseudomonas fluorescens, immobilized on soft polyvinyl chloride granules containing up to 35% softeners as carbon source, was used for simultaneous removal of nitrate and heavy metals. In typical continuous column operation, a 100 mg/L nitrate input solution was reduced to a 20 mg/L output at a feeding rate of 1500 mL/h, with a capacity of 14 kg/day/m(3), and with an efficiency of 79%. In the same column, Pb(NO3)2 concentration was reduced from 1.0 to 0.05-0.1 mg/L and ZnSO4 concentration was reduced from 10 to 5 mg/L.Pseudomonas aeruginosa immobilized on an O2 plasma-treated melt blown polypropylene web was used for removing 95% of a 1.7 nCi PuCl4 activity from a nuclear plant waste water in a batch operation. PMID- 24233651 TI - Nucleotide sequence diversity in Velvet tobacco mottle virus: a virus with a unique Australian pathosystem. AB - Velvet tobacco mottle virus (VTMoV) is a naturally occurring mirid-transmitted sobemovirus of native velvet tobacco (Nicotiana velutina) plants in the Australian arid zone. We have sequenced the coding region of a typical field isolate of VTMoV (isolate I-17-04, satellite-plus) and show that it differed by nine polymorphisms from the previously sequenced atypical 'satellite-minus' variant VTMoV-K1 (represented here as L-K1-04), while retaining the same genomic and amino acid sequence motifs. We also report that although L-K1-04 was confirmed to be free of detectable satellite RNA by gel electrophoretic assay, the satellite sequence was detected in it by RT-PCR assay. Nucleotide sequence variation among the RNA-dependent RNA polymerase open reading frames of 15 field and laboratory isolates identified four phylogenetic groups, but these did not show a pattern related to site or time of sampling. This result would be consistent with nucleotide sequence variants of VTMoV being dispersed widely by migrating adult mirid vectors. PMID- 24233654 TI - The analysis of serum urate utilizing immobilized uricase. AB - The evaluation of a method for the estimation of serum urate using immobilized uricase is described, the resultant hydrogen peroxide produced being measured by the oxidative coupling of 3,5-dichloro-2-hydroxybenzenesulfonate and 4 aminophenazone in the presence of peroxidase.A continuous-flow analysis system incorporating the uricase tube was established, and the results obtained were correlated with an automated phosphotungstate method and with a manual uricase method employing an LKB 8600 Rate Reaction Analyser. The effect of ascorbic acid on the analysis of serum urate and the elimination of this interference by the use of ascorbate oxidase was also investigated.The precision, correlation, and high specificity obtained show that this is a satisfactory method for use in routine clinical laboratory works. PMID- 24233655 TI - Determination of intrinsic properties of immobilized enzymes : 1. Kinetic studies on sepharose-staphylococcal nuclease in the absence of diffusional limitations. AB - Staphylococcal nuclease has been insolubilized, directly through its amino groups, on CNBr-activated Sepharose 2B. For kinetic studies, a small substrate (thymidine 5'-(p-nitrophenyl phosphate) 3'-phosphate) has been used to measure the hydrolytic activity. With this system the absence of diffusional limitation has been proven. Eadie-Hofstee analysis of the data has been employed to determine the intrinsic kinetic constants of the insolubilized enzyme. Thek cat pH andK M-pH profiles and the activation energies are similar for the soluble and for the insolubilized nuclease. At the same time conditions are established in which a stirred batch reactor containing particles of insolubilized nuclease behaves as an open system. PMID- 24233656 TI - Determination of intrinsic properties of immobilized enzymes : 2. Kinetic studies on sepharose-staphylococcal nuclease in the presence of diffusional limitations. AB - Using a small substrate (thymidine 5'-(p-nitrophenyl phosphate) 3'-phosphate), the kinetics of staphylococcal nuclease insolubilized on CNBr-activated Sepharoses 4B and 6B are affected by internal diffusional limitations. Since we demonstrate that we are working under conditions in which external mass-transfer resistances do not influence the reaction rate, we propose a simple theoretical model that considers only the case of mixed enzymic reaction-internal diffusion kinetics. In the Eadie-Hofstee plots we find very good agreement between theory and experiment. The model accounts very well for the results obtained by changing support texture, reaction conditions, and/or enzyme concentration in the insoluble derivatives, variables that modify the diffusional restrictions of the system. PMID- 24233657 TI - Recent advances in homogeneous and separation-free enzyme immunoassays. PMID- 24233659 TI - Utilization and impact of repeat biopsy for follicular lesion/atypia of undetermined significance. AB - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) created a new diagnostic category,follicular lesion/atypia of undetermined significance(FLUS/AUS). The recommended management of FLUS/AUS lesions is repeat biopsy to re-classify the lesion and guide therapy. Prior surgical studies suggest a higher than expected malignancy rate for FLUS/AUS. The present study evaluates a large institutional experience with all FLUS/AUS lesions analyzing use and impact of repeat biopsy. METHODS: A total of 322 patients with FLUS/AUS cytology have been retrospectively identified since adoption of the BSRTC (2/2009 6/2012). Patient demographics, the results of clinical follow-up, repeat biopsy, or surgical pathology results were evaluated. RESULTS: Among the 322 patients, 16 had concurrent cytology of higher acuity and were excluded. For the remaining 306 patients, 101 (33 %) underwent repeat biopsy, yielding 49 (48.5 %) with FLUS/AUS, 43 (42.5 %)with benign cytology, and 9 (9 %) with higher acuity cytology. Among the 205 patients without repeat biopsy,117 (57 %) chose thyroidectomy, and 88 (43 %) are being observed. Overall, 170/306 (55.6 %) patients underwent surgery to remove the index lesion, yielding a malignancy rate of 16.5 %. In contrast, the malignancy rate for the entire cohort was 28/306 (9 %). CONCLUSIONS: Repeat biopsy was underutilized in FLUS/AUS cases. Repeat biopsy allows a significant proportion of FLUS/AUS patients without other indications for surgery to move to surveillance. In patients who have indications for thyroidectomy regardless of FLUS/AUS results,repeat biopsy does not appear necessary. Malignancy and thyroidectomy rates were similar among patients who did or did not have a repeat biopsy. Further data must be obtained to determine the long-term outcomes for surveillance of FLUS/AUS lesions in patients who do not undergo surgical removal. PMID- 24233658 TI - Prospective study to compare peri-operative hemodynamic alterations following preparation for pheochromocytoma surgery by phenoxybenzamine or prazosin. AB - BACKGROUND: Prospective studies comparing the efficacy of selective versus nonselective alpha blockers for preoperative preparation of pheochromocytoma (PCC) are lacking. In this prospective nonrandomized study, we compared the outcome of preoperative preparation with phenoxybenzamine (PBZ) and prazosin (PRZ) in terms of perioperative hemodynamic alterations. METHODS: The study was conducted at a tertiary referral center from July 2010 to December 2012. Thirty two patients with PCC underwent operation after adequate preparation with PBZ (n = 15) or PRZ (n = 17). Five pediatric and adolescent patients were excluded because of different hemodynamics in this population. Perioperative monitoring was done for pulse rate (PR) and blood pressure(BP) alterations, occurrence of arrhythmias, and time taken to achieve hemodynamic stability. Groups were compared with the Mann-Whitney test, Student's t test, and the chi2 test as applicable. RESULTS: Patients in the two groups were similar in age,gender, 24 h urinary metanephrine and normetanephrine levels, and type of procedure. Patients prepared with PRZ had significantly more intraoperative episodes of transient hypertension (systolic BP >= 160 mmHg) and hypertensive urgency (BP >180/110 mmHg) (p 0.02, 0.03, respectively). More patients receiving PRZ suffered from transient severe hypertension (SBP >= 220 mmHg) (p 0.03). The PRZ group also had more median maximum SBP (233 mmHg vs PBZ 181.5 mmHg) (p = 0.01) and lesser median minimum SBP (71 mmHg vs PBZ 78 mmHg) (p 0.03). No significant differences were found between the study groups for changes in PR, postoperative BP alterations,occurrence of arrhythmias, and time taken to achieve hemodynamic stability. CONCLUSIONS: PBZ was found superior to PRZ in having fewer intraoperative hemodynamic fluctuations. PMID- 24233660 TI - Indication for liver transplantation in young patients with small intestinal NETs is rare? AB - BACKGROUND: A majority of patients with small intestinal neuroendocrine tumors (SI-NETs) present with or develop liver metastases (LM). A number of treatments for LM are used clinically, including liver transplantation (LTx). Indications for LTx are under debate; young age(<65 years), absence of extrahepatic disease, resected primary tumor and limited extent of LM have been suggested as inclusion criteria for LTx with the aim to optimize outcome. MATERIALS AND METHODS: From our series of 672 patients with SI-NET treated at the University Hospital in Uppsala between 1985 and 2012, we identified 78 patients according to the following criteria: <65 years of age, locoregional surgery (LRS) of the primary tumor and mesenteric metastases successfully performed, LM present but no extrahepatic disease. Baseline was chosen as the first date the following points were met: First visit to our center,LRS performed, LM present. The patients underwent treatment according to the standard clinical protocols at our center, and during this time period we did not perform or refer any SI-NET patients for LTx. Kaplan-Meier survival analyses were performed in three different groups based on hypothetical criteria for LTx. RESULTS: Five-year overall survival rates for patients <65 years (n = 78) and <55 years (n = 36) of age were 84 +/- 8 and 92 +/- 9 %, respectively. For patients fulfilling the Milan criteria (n = 33) the 5-year survival was 97 +/- 6 %. CONCLUSIONS: Most young patients (<65 years) with SINET and LM have a favorable survival with standardized multimodality treatment. Indeed, most survival figures reported after LTx of NET do not surpass these figures. PMID- 24233662 TI - Association between serum thyrotropin concentration and growth of asymptomatic papillary thyroid microcarcinoma. AB - BACKGROUND: Thyrotropin (TSH) is a known thyroid growth factor. Several studies have suggested its potential role in carcinogenesis and the progression of differentiated thyroid carcinoma. We have been conducting a prospective trial of nonsurgical observation for asymptomatic papillary thyroid microcarcinoma (PMC) since 1995. The aim of this study was to investigate whether serum TSH concentrations can be used to predict PMC growth. METHODS: This study examined 415 asymptomatic PMCs.Three hundred twenty-two patients decided to undergo nonsurgical observation by ultrasonography and were followed for >= 2 years. RESULTS: After a mean of 6.5 years of observation (range 2-22 years), 25 lesions (6 %) had increased in size, 377(91 %) showed no change and 13 (3 %) had decreased in size. Both baseline TSH and mean TSH during follow-up for PMC that increased in size did not differ significantly from those lesions that were unchanged or decreased in size. Increases in size were seen in 0 of 18 (0 %), 15 of 260(6 %), 10 of 126 (8 %), and 0 of 11 (0 %) for PMCs with baseline TSH <0.50, 0.50-1.99, 2.00-3.99, and >= 4.00 mIU/L, respectively. A logistic regression model analyzing the association between baseline TSH and outcome showed an odds ratio of 1.01 (95 % confidence interval [CI], 0.66-1.29). No significant correlations were apparent between mean TSH during follow-up and change in PMC volume (r = 0.019, p = 0.70). CONCLUSIONS: No significant association between TSH and tumor progression was verified during the nonsurgical observation trial for PMC. TSH is not a good predictor of PMC growth. PMID- 24233664 TI - A simulation model for the effect of predation on bacteria in continuous culture. AB - A simulation model was developed for the carbon (C), nitrogen (N), and phosphorus (P) content of bacteria and their medium in a chemostat. Cell components distinguished included the structural component, synthetic machinery, building blocks and intermediates, C reserves, ammonium (NH4), orthophosphate (PO4), and polyphosphate. Growth, incorporation of substrates, and production of waste products were related to physiological status, as indicated by the amounts of various cell components. The model was fitted to data from chemostats on the chemical composition of bacteria growing in C-, N-, and P-limiting media and was used to explore the consequences of predation on bacterial populations. In C limiting media predation (without the return of nutrients to the medium by the predator) increased NH4 uptake in spite of a decrease in bacterial biomass. In N limiting media predation decreased both biomass and the rate of N uptake. These results were accounted for by the effect of growth rate on bacterial N demand. In C-limiting media the return of NH4 and PO4 by the predator did not change the effect of predation on bacteria. But in N-limiting media the return of nutrients decreased the effect of predation on biomass, and stimulated respiration and NH4 uptake by the bacteria. The effect of growth rate on the chemical composition of bacteria was proposed as a possible explanation of the stimulatory effect of predators on bacteria. PMID- 24233665 TI - Simultaneous measurement of phosphorus and carbon uptake in Lake Kinneret by multiple isotopic labeling and differential filtration. AB - Differential filtration and multiple isotopic labeling were combined to study the uptake of [(14)C]bicarbonate, [(14)C]glucose, and [(32)P]orthophosphate by microplakton in Lake Kinneret, Israel. Short-term (4 hr) uptake experiments showed seasonal changes in the size distributions of organisms taking up inorganic carbon, glucose carbon, and orthophosphate in the lake water. In a time course experiment of 48 hr (Jan 1976) most, but not all, of the photosynthetic activity (average 72%) and a similar fraction of chlorophyll (72%) were associated with organisms retained on 3-MUm Nuclepore filters (retention on 0.4 MUm filters was 100%). About 90% of the organisms that assimilated glucose passed through 3-MUm filters. Photosynthetic carbon fixation, dark carbon uptake, and heterotrophic uptake of glucose carbon accounted for 99%, 1%, and 1%, respectively, of the total net carbon assimilated during the first 6 hours. Radioactive phosphorus showed an initial rapid uptake into particles, which was not affected by light or dark. We suggest that this methodology has a wide potential for elucidating the flux of nutrients into various components of the microplankton and in characterizing different aquatic environments. PMID- 24233663 TI - Transdisciplinary approach to restore pancreatic islet function. AB - The focus of our research is on islet immunobiology. We are exploring novel strategies that could be of assistance in the treatment and prevention of type 1 diabetes, as well as in the restoration of metabolic control via transplantation of insulin producing cells (i.e., islet cells). The multiple facets of diabetes and beta-cell replacement encompass different complementary disciplines, such as immunology, cell biology, pharmacology, and bioengineering, among others. Through their interaction and integration, a transdisciplinary dimension is needed in order to address and overcome all aspects of the complex puzzle toward a successful clinical translation of a biological cure for diabetes. PMID- 24233666 TI - Isolation and characterization of a high molecular weight antibiotic produced by a marine bacterium. AB - Many marine bacteria demonstrate antibiotic activity against organisms of terrestrial origin. Low molecular weight antibiotics have been extracted and, in some cases, purified, but few attempts have been made to isolate high molecular weight antibiotics produced by marine bacteria. In the study reported here, a high molecular weight antibiotic was extracted from whole cells ofAlteromonas strain P18 (NCMB 1890) grown on 2216E medium. Purification included ammonium sulfate precipitation, ultracentrifugation, chromatography on DEAE cellulose, and gel filtration on Ultrogel. A rapid method for measuring specific activity of the antibiotic was developed. PMID- 24233667 TI - Aerobic carboxydobacteria. AB - Bacterial consumption of CO, a major atmospheric pollutant, has been described in the literature long ago, but often with controversial data. Attempts were made, therefore, to isolate and study a broader spectrum of aerobic CO bacteria in order to better understand their ecology.About 100 samples from various locations in the USSR (water, mud, junkyard, or garden, soil etc.) were inoculated into mineral medium and incubated under 80% CO and 20% O2. Such enrichments yielded a large number of strains representing 5-6 different bacterial species. The highest number of CO utilizers came from fresh samples of polluted, moist soil or mud. Some mixed cultures were composed of vitamin-dependent bacteria living together in a state of protocooperation. Seven strains (previously already partially described) were studied in greater detail. They are regarded as "carboxydobacteria." Six carboxydobacteria also utilized hydrogen, but none of the 7 cultures grew with methane or formate. The optimal concentration of, and sensitivity to, CO varied with the strains. Reducedvs. oxidized spectra revealed in all cultures the presence ofb-, c-, anda-type cytochromes, indicating a functioning electron transport chain when grown under CO. Isotope experiments with(14)C indicated that CO was assimilated only after oxidation to CO2, the pathway being the normal Calvin cycle reaction sequence as observed in other chemolithotrophs. The key enzymes of this sequence were shown to be present and active.Organotrophic growth of carboxydobacteria was obtained with a number of compounds such as organic acids, primary alcohols, carbohydrates, and amino acids. A description of properties of the 7 test strains is given. Their ecological niche(s) seem to be where facultatively anaerobic bacteria produce organic intermediates as well as H2 and CO. Pellicle formation indicates their presence on the water surface (neuston layer). Relationships with hydrogen oxidizing bacteria are discussed and explained on ecological grounds. PMID- 24233668 TI - The photobioluminometer, an instrument for the study of ecological factors affecting photosynthesis. AB - An instrument for measurement of bioluminescence and photosynthesis is described. It may be used to detect chemicals toxic to luminous bacteria or to measure photosynthetic oxygen production of algae in mixed culture with bacteria. The latter technique has been used to study the effect on algal photosynthesis of environmental factors such as light quality, temperature, and salinity, and to study the factors affecting chlorophyll synthesis. The technique is ideal for rapid detection of photosynthesis-inhibiting herbicides and other toxic substances in water. PMID- 24233669 TI - Effects of paraquat on selected microbial activities in soil. AB - Paraquat, applied as Gramoxone, to a nonamended sandy loam soil at five times the suggested field application rate (10 lb/A ~ 115MUg/cm(2)) increased the numbers of bacteria, actinomycetes, and fungi during a 14-day incubation at 25 degrees C. This increase was attributed to the use of compounds in the Gramoxone formulation rather than the use of paraquat. Treatment at one and five times the normal rate reduced CO2 evolution by 44% and 67%, respectively, in soil amended with 2% glucose during a 12-day incubation. Similar treatments reduced CO2 evolution in 1% straw-amended soil by 39% and 58%, respectively, during a 28-day incubation. Cellulose decomposition of cotton duck containing 13 and 176MUg of paraquat per milligram of material was inhibited for 15 and 28 days, respectively, in soil containing a large population of cellulolytic microorganisms. A concentration of 5000MUg/gm of paraquat was necessary to inhibit nitrification in soil by 44% druing a 28-day incubation at 20 degrees C. Paraquat inhibited C2H2 reduction in artificial aggregates of soil amended with 2% glucose and incubated anaerobically at 25 degrees C. Nitrogenase activity in aggregates was inhibited by 43% and 52% at concentrations of 580 and 720MUg/gm of paraquat respectively. The inhibitory effects of the herbicide were reduced when soil was amended with organic matter in the form of peat or straw. The availability of paraquat controlled the toxicity of the herbicide to soil microorganisms. PMID- 24233670 TI - Use of membrane filters for the enumeration of autotrophic thiobacilli. AB - A new membrane filter technique for field use was developed for the enumeration of either aerobic or anaerobic, autotrophic, sulfur-oxidizing bacteria in waters and soils. Immediately after collection, samples were filtered through sulfur coated filters and incubated in selective media. Acidification or gas evolution was used as a growth indicator of aerobic and anaerobic thiobacilli, respectively, and related to the initial number of cells deposited on the filter. PMID- 24233671 TI - Potential aversive compounds in leafy spurge for ruminants and rats. AB - Several wild and domestic ruminant species and horses apparently will not consume leafy spurge (Euphorbia esula) while grazing range and pasture lands. It has been demonstrated that leafy spurge can elicit conditioned food aversions in cattle and sheep, and the aversion-eliciting capacity of leafy spurge may account for why cattle seldom graze this nutritious plant and why sheep may not readily consume it at some locations. The identity of the aversive compound(s) in leafy spurge is unknown, but several different diterpenoid ingenol esters have been isolated from its tissues, and we suspect that one or more ingenol esters may be aversion-eliciting compounds in leafy spurge. The objectives of this study were to determine whether or not leafy spurge is aversive to laboratory rats and if a crude acetone extract of leafy spurge, presumably containing ingenol esters and other phytochemicals, could generate an aversive response in sheep and laboratory rats. An additional objective was to determine whether or not a particular ingenol monobenzoate, which may be similar to ingenol esters in leafy spurge, might also elicit an aversive response from rats. Rats exhibited food aversions associated with leafy spurge (P < 0.05). An acetone extract of leafy spurge induced conditioned food aversions in both sheep and rats (P < 0.01). The ingenol 3-monobenzoate also induced conditioned food aversions in rats (P < 0.01). Our interpretation of these data is that rats can be used as a model for cattle and sheep with respect to their aversion to leafy spurge ingestion. Additionally, we suggest that one or more ingenol esters may be aversion-inducing agents in leafy spurge. However, others may exist in leafy spurge that are also aversive or are the only or prime aversive chemicals. PMID- 24233672 TI - Volatile ketones from interdigital glands of black-tailed deer,Odocileus hemionus columbianus. AB - Three volatile ketones, 2-tridecanone, (E)-3-tridecen-2-one and (E)-4-tridecen-2 one were identified in interdigital gland extracts from black-tailed deer,Odocoileus hemionus columbianus. The major compound, (E)-3-tridecen-2-one, inhibited the growth of several species of fungi and grampositive bacteria. The bacterium,Propionibacterium acnes, and the fungus,Trichophyton mentagrophytes required a minimum concentration (MIC) of 12.5 ug/ml and 25 ug/ml, respectively, for inhibition, (E)-3-Tridecen-2-one represents a new class of lipid antibiotics found on animal skin. The second major compound is this secretion, 2-tridecanone, was not active against any of the organisms tested. PMID- 24233673 TI - Identification of an attractant for the caneborerSesamia grisescens walker (Lepidoptera: Noctuidae). AB - The composition of the sex pheromone ofSesamia grisescens was investigated using gas chromatography, electroantennograms, and field trapping. (Z)-11-Hexadecenyl acetate and (Z)-11-hexadecenol were identified in field tests as the major attractants. Trapping trials identified a 3:2 blend of these compounds as the most effective bait. Gas chromatography indicated the presence of hexadecyl acetate. (Z)-9-hexadecenyl acetate, (Z)-9-hexadecenol, and (E)-11-hexadecenyl acetate in the pheromone gland, but these compounds had no significant effect on trap catches when added to the major components. Traps baited with the major components in a 1:1 ratio caught more male moths than traps baited with virgin females. PMID- 24233674 TI - Variation among and within mountain birch trees in foliage phenols, carbohydrates, and amino acids, and in growth ofEpirrita autumnata larvae. AB - Leaf quality of the mountain birch (Betula pubescens ssp.tortuosa) for herbivores was studied at several hierarchical levels: among trees, among ramets within trees, among branches within ramets, and among short shoots within branches. The experimental units at each level were chosen randomly. The indices of leaf quality were the growth rate of the larvae of a geometrid,Epirrita autumnata, and certain biochemical traits of the leaves (total phenolics and individual phenolic compounds, total carbohydrates and individual sugars, free and protein-bound amino acids). We also discuss relationships between larval growth rate and biochemical foliage traits. Larval growth rates during two successive years correlated positively at the level of tree, the ramet, and the branch, indicating that the relationships in leaf quality remained constant between seasons both among and within trees. The distribution of variation at different hierarchical levels depended on the trait in question. In the case of larval growth rate, ramets and short shoots accounted for most of the explained variation. In the case of biochemical compounds, trees accounted for most of the variance in the content of total phenolics and individual low-molecular-weight phenolics. In the content of carbohydrates (total carbohydrates, starch, fructose, glucose, and sucrose) and amino acids, variation among branches was generally larger than variation among trees. Variation among ramets was low for most compounds. No single leaf trait played a paramount role in larval growth. Secondary compounds, represented by phenolic compounds, or primary metabolites, particularly sugars, may both be important in determining the suitability of birch leaves for larvae. If phenols are causally more important, genet-specific analyses of foliage chemistry are needed. If sugars are of primary importance, within-genet sampling and analysis of foliage chemistry are necessary. PMID- 24233675 TI - Herbivore avoidance of digitalis extracts is not mediated by cardiac glycosides. AB - This study was conducted to determine whether avoidance of digitalis (Digitalis purpurea) by mountain beaver (Aplodontia rufa) is induced by toxic cardiac glycosides. High-performance liquid chromatography and behavioral assays were used to relate animal responses with the presence of common cardiac glycosides in several digitalis extracts. Statistical analyses of multiple-choice tests showed no correlation between cardiac glycoside content and mountain beaver avoidance of apple cubes treated with digitalis extracts. Therefore, we concluded that known toxic cardiac glycosides were not responsible for chemosensory cues that inhibited intake of food treated with digitalis extracts. These results suggest that digitalis is a source of an effective nontoxic herbivore repellent. PMID- 24233676 TI - Volatile compounds induced by herbivory act as aggregation kairomones for the Japanese beetle (Popillia japonica Newman). AB - The Japanese beetle is a polyphagous insect that typically aggregates on preferred host plants in the field. We studied the response of Japanese beetles to artificial damage, fresh feeding damage, and overnight feeding damage to test the hypothesis that beetles are attracted to feeding-induced volatiles. Crabapple leaves that had been damaged overnight by Japanese beetles or fall webworms attracted significantly more Japanese beetles than did undamaged leaves. Artificially damaged leaves or leaves freshly damaged by Japanese beetles, however, were not significantly more attractive than undamaged leaves. Leaves that had been damaged overnight by Japanese beetles or fall webworms produced a complex mixture of aliphatic compounds, phenylpropanoid-derived compounds, and terpenoids. In comparison, artificially damaged leaves or leaves with fresh Japanese beetle feeding damage generated a less complex blend of volatiles, mainly consisting of green-leaf odors. Feeding-induced odors may facilitate host location and/or mate finding by the Japanese beetle. PMID- 24233677 TI - Early warning in the predation sequence: A disturbance pheromone in Iowa darters (Etheostoma exile). AB - The probability of prey avoiding a predator's attack should increase if the predator's presence is detected at an early stage in the predation sequence. In this study, we tested whether threatened Iowa darters (Etheostoma exile) release disturbance pheromones that warn conspecifics of the presence of predation threat. Pairs of aquaria were visually isolated from one another, but connected chemically by water circulating between them. Darters in one aquarium were observed before and after darters in the other aquarium were chased with a model predator. In control tests, the model was moved in the same manner but there were no darters in the upstream tank. Darters receiving water from threatened fish increased vigilance behavior and decreased movement. Vigilant fish raised their head above the substratum, propping themselves up on their pectoral fins and/or arching their neck dorsally, pointing the snout upward. Exposure to water from disturbed darters suppressed exploratory behavior and resulted in movement by short rapid hops that ended abruptly in a rigid, alert posture. This study suggests that Iowa darters release a disturbance pheromone that can provide conspecifics with an early warning of predation risk. PMID- 24233678 TI - Rates of urine excretion by house mouse (Mus domesticus): Differences by age, sex, social status, and reproductive condition. AB - A series of five experiments was used to test hypotheses about factors affecting excreted urine output per day in male and female house mice (Mus domesticus). Urine was collected in metabolism cages over a 24-hr period. Male house mice excrete urine at a rate 1.5-2.0 times that of females. Daily average urine output increases with age for both sexes and for mice of the same age; urine output per day is correlated with body mass. Females in estrus produce more urine than females in diestrus. Urine output per day increases during the latter two thirds of pregnancy and remains high throughout lactation. Density does not influence urine output per day for either sex over the range of densities tested. Castration reduces urine output per day in male mice, but ovariectomy in females does not alter rates of urine production. Dominant males produce more urine than subordinate males, but there are no similar effects for female mice. The findings have potential implications for our understanding of the functional and ecological uses of urine by house mice. PMID- 24233679 TI - Substrate specificity of acetyltransferase and reductase enzyme systems used in pheromone biosynthesis by Asian corn borer,Ostrinia furnacalis. AB - The substrate specificity of the acetyltransferase and the reductase enzyme systems used byOstrinia furnacalis (Lepidoptera: Pyralidae) in pheromone biosynthesis was studied in vivo by topical application of precursors to pheromone glands. Each of the tetradecenols, varying in double bond position (from 7 to 13) and geometry of the double bond, was converted to the corresponding acetate by the acetyltransferase. The similarity in the conversion rates of all tested fatty alcohols indicated that the acetyltransferase has a low substrate specificity. Most of the corresponding tetradecenoic acids could also be converted to the respective acetates. However, very different conversion rates among the tested fatty acids demonstrated that the reductase system has a higher substrate specificity than the acetyltransferase. The conversion rates of mostE isomers were higher than those of the correspondingZ isomers, except for the (Delta)-11-tetradecenoic acids, in which much moreZ isomer was converted to the product. Saturated tetradecanoic acid was converted to the corresponding acetate at a high rate; the shorter homolog, tridecanoic acid, was converted at a lower rate (56%), and conversion to the respective acetates of the longer homolog, pentadecanoic and hexadecanoic acids, was insignificant (<5%). The results from the present study showed that specificity of pheromone production is to a large extent controlled by the pheromone gland reductase system. PMID- 24233680 TI - Foliar oxidative stress and insect herbivory: Primary compounds, secondary metabolites, and reactive oxygen species as components of induced resistance. AB - Oxidative responses of plants to pathogens and other environmental stresses have received considerable recent attention. We propose that an oxidative response also occurs following attack by herbivores. Our data strongly indicate a shift in the oxidative status of soybean following herbivory by the insectHelicoverpa zea. Herbivory caused significant increases in lipid peroxidation and .OH radical formation. The activity of several oxidative enzymes including lipoxygenases, peroxidase, diamine oxidase, ascorbate oxidase, and NADH oxidase I increased after herbivory on soybean. The enhanced production of phenolic compounds is indicated by an increase in the activity of phenylalanine ammonia lyase in wounded tissues. On the other hand, the level of soybean foliar antioxidants such as ascorbic acid, total carotenoids, nonprotein thiols, and catalase decreased significantly following herbivory. These results implicate primary compounds (e.g., ascorbic acid, proteins), secondary metabolites (e.g., phenolics), and reactive oxygen species (e.g., hydroxyl radical, hydrogen peroxide) as multiple components of induced resistance. The oxidative changes in the host plant correspond with increased oxidative damage in the midgut of insects feeding on previously wounded plants. Decreases in nonprotein thiols and reduced ascorbic acid occurred in midgut epithelial tissue from insects feeding on wounded plants compared to the insects on control plants. In contrast, midgut hydroperoxides and dehydroascorbic acid concentrations were greater in insects on wounded plants compared to their counterparts on control plants. We conclude that oxidative responses in soybean may have both positive and negative effects upon the host plant: a decrease in herbivory and an increase in oxidative damage to the plant. The salient benefit to the plant, in terms of insect resistance, is the relative balance between these opposing effects. PMID- 24233681 TI - A flavonoid glucoside, phellamurin, regulates differential oviposition on a rutaceous plant,Phellodendron amurense, by two sympatric swallowtail butterflies,Papilio protenor andP. xuthus: The front line of a coevolutionary arms race? AB - We studied the chemical basis for the differential acceptance of a rutaceous plant.Phellodendron amurense, by ovipositing females of two sympatricPapilio butterflies,P. protenor andP. xuthus, that have a very similar host range.P. amurense, on which larvae of both species perform well, was rejected byP. protenor females but was marginally accepted byP. xuthus, even though water soluble fraction of this plant elicited significant ovipositional responses from the two species. A prenylated dihydroflavonol glucoside, 3,5,7,4'-tetrahydroxy-8 (3-methylbut-2-enyl)flavanone-7-O-beta-glucoside (phellamurin), was identified as a dominant active substance that deters oviposition.P. protenor responded highly sensitively to phellamurin, whereasP. xuthus was less susceptible and was affected conspicuously only at higher concentrations than that found in living plants, thereby accounting for their differential responses toP. amurense. InP. protenor, the deterrent effect of phellamurin was considered to outweigh the activity of coexisting stimulant(s) at the concentrations actually present in the foliage, resulting in avoidance of this plant. The phellamurin content in the foliage amounted to as much as 1.8% of the fresh weight, which is far higher than the average levels of flavonoids present in other major host plants ofPapilio. The dose-response experiments demonstrated that unacceptability ofP. amurense forP. protenor was attributable largely to such a high concentration of phellamurin. These results appear to provide information on possible coevolutionary interactions between herbivores and plants and also on the potential for shifts in host affiliation. PMID- 24233682 TI - A neolignoid feeding deterrent againstLuehdorfia puziloi larvae (lepidoptera: Papilionidae) fromHeterotropa aspera, a host plant of sibling species,L. japonica. AB - A feeding deterrent against larvae of a papilionid butterfly,Luehdorfia puziloi (Parnassiinae), a specialist onAsiasarum plants (Aristolochiaceae), was isolated from another aristolochiaceous plant,Heterotropa aspera. Antifeedant activity was exhibited by then-hexane-soluble fraction that proved to contain at least two active components. One of the deterrents was identified as a neolignan compound, asatone. The concentration of asatone inH. aspera was estimated at approximately 225 ppm, and larval feeding ofL. puziloi was significantly deterred at concentrations over 90 ppm. By contrast, asatone was not detectable (< 1 ppm, if any) in its host plant,Asiasarum sieboldii. PMID- 24233683 TI - Aggregation pheromone of coconut rhinoceros beetle,Oryctes rhinoceros (L.) (coleoptera: Scarabaeidae). AB - Male coconut rhinoceros beetles,Oryctes rhinoceros (L.), produce three sex specific compounds, ethyl 4-methyloctanoate, ethyl 4-methylheptanoate, and 4 methyloctanoic acid, the first of which is an aggregation pheromone. Synthesis of these compounds involving conjugate addition of organocuprates to ethyl acrylate is reported. In field trapping experiments, (4S)-ethyl 4-methyloctanoate and the racemic mixture were equally attractive and 10 times more effective in attracting beetles than ethyl chrysanthemumate, a previously recommended attractant. Ethyl 4 methylheptanoate was as attractive as ethyl chrysanthemumate and more attractive than 4-methyloctanoic acid, but further studies are required before it can be classed as an aggregation pheromone. Compared to ethyl 4-methyloctanoate alone, combinations of the three male-produced compounds did not increase attraction, whereas addition of freshly rotting oil palm fruit bunches to pheromone-baited traps significantly enhanced attraction. With increasing dose, captures ofO. rhinoceros increased, but doses of 6, 9, and 18 mg/day were competitive with 30 mg/day lures. Newly designed vane traps were more effective in capturing beetles than were barrier or pitfall traps. Results of this study indicate that there is potential for using ethyl 4-methyloctanoate in operational programs to controlO. rhinoceros in oil palm plantations. PMID- 24233684 TI - An evaluation of repellents to suppress browsing by possums. AB - The efficacy in feeding suppression trials with possums (Trichosorus vulpecula Kerr) of six synthetic odorous chemicals uniquely associated with various of the Mustelidae species and of the red fox (Vulpes vulpes) has been evaluated with respect to several proprietary repellents. The predator odors, two proprietary repellents, and two other repellent formulations (olive oil in petroleum jelly and a synthetic fermented egg odor cocktail) were applied as 5% w/v solutions in paraffin to the foliage ofPinus radiata seedlings and the extent of browse compared with that on seedlings treated with Treepel, an effective egg-based repellent already available commercially. All four of the mustelid predator odors [(?)-2-n-propylthietane, (?)-3-n-propyl-1,2-dithiolane, 2,2-dimethylthietane, and 3,3-dimethyl-1,2-dithiolane] and the volatile compound from fox urine (Delta(3) isopentenyl methyl sulfide) were shown to be more or at least equally effective compared to Treepel. This was true also of one commercial repellent Gori, which contained bitrex and the synthetic fermented egg formulation. The most effective compounds will be evaluated when administered with adhesives and surfactants in the further development of possum repellents with longer field lives. PMID- 24233685 TI - Structure-related insect antifeedant and growth regulating activities of some limonoids. AB - Insect antifeedant and growth-regulating activities of 22 limonoids (both natural and their derivatives) againstSpodoptera litura were studied to understand the structure-related bioactivities of the limonoids. The C-seco limonoids (azadirachtins A, B, D, H, and I) were the most effective compounds as a group, while the intact limonoids (cedrelone and its derivatives) were the least effective. The cyclohexenone A ring and thealpha-hydroxy enone group in the B ring appear to be important for antifeedant activity. The presence of a cyclohexenone or 1,2-epoxide in the A ring coupled with analpha-hydroxy enone in the B ring correlated well with growth regulatory activity. An acetoxy at C-7 instead ofalpha-hydroxy enone and perhaps the carbonyl at C-16 increase growth regulatory activity. Absence of 14-15 epoxide may not drastically reduce antifeedant activity and growth regulatory activity. PMID- 24233686 TI - Chemical and experiential basis for rejection ofTropaeolum majus byPieris rapae larvae. AB - Rejection of nasturtium,Tropaeolum majus, by cabbage-reared larvae ofPieris rapae has been explained by the presence of feeding deterrents in the nastrutium foliage. Sensitivity to the deterrents develops as neonate larvae feed on cabbage. The most prominent deterrent compound, which is present in nasturtium at a concentration of 40 mg/100 g fresh leaves, was identified as chlorogenic acid. When neonate larvae were fed on a cabbage leaf treated with high concentrations of deterrent-containing extracts of nasturtium foliage, they remained insensitive to the deterrents, so they accepted nasturtium when transferred as second instars. When neonate larvae were reared on a cabbage leaf treated with 0.1 mg chlorogenic acid, ca. 35% of the second instars accepted nasturtium. Similar dietary exposure of neonates to the subunits of chlorogenic acid, caffeic acid and quinic, acid resulted in much less or no effect on the rejection behavior of second instars. The results suggest that the combined effects of specific chemical constituents of nasturtium can explain the rejection of this plant by larvae ofP. rapae, but if larvae are continuously exposed to these compounds immediately after hatching, they apparently become habituated to the feeding deterrents. The lack of activity of the subunits of chlorogenic acid suggests that specific structural features are necessary for a dietary constituent to cause such habituation or suppression of sensitivity development. PMID- 24233687 TI - Structure, chirality, and field testing of a male-produced aggregation pheromone of Asian palm weevilRhynchophorus bilineatus (Montr.) (Coleoptera: Curculionidae). AB - 4-Methyl-5-nonanol is a male-produced aggregation pheromone of the Asian palm weevil,Rhynchophorus bilineatus (Montr.). The pheromone was identified by coupled gas chromatographic-electroantennographic detection (GC-EAD) and coupled GC-mass spectrometric (MS) analyses of male-and female-produced volatiles. Analyses by GC EAD and GC-MS of weevil-produced and stereoselectively synthesized isomers of 4 methyl-5-nonanol on a Cyclodex B column, which separated isomers with baseline resolution, revealed that only (4S,5S)-4-methyl-5-nonanol is EAD active and produced by the males. In field experiments in Papua New Guinea, (4S,5S)-4-methyl 5-nonanol and a racemic mixture of disatereoisomers of it enhanced attraction of male and female weevils to sugarcane-baited traps. (4S,5S)-4-Methyl-5-nonanol is also an aggregation pheromone of two other Asian palm weevils.R. ferrugineus (Oliv.) andR. vulneratus (Panz.). The stereoisomeric mixture of 4-methyl-5 nonanol is currently used to manage populations ofR. bilineatus in Papua New Guinea. PMID- 24233688 TI - Plant phylodiversity enhances soil microbial productivity in facilitation-driven communities. AB - The classical relationship between biodiversity and ecosystem functioning can be better understood when the phylogenetic component of biodiversity is considered. We linked plant phylodiversity and ecosystem functioning in a water-limited gypsum ecosystem driven by plant facilitation. We tested whether (1) plant facilitation relaxes the abiotic filter imposed by gypsum, allowing the establishment of non-gypsophyte plant species, and consequently increasing plant phylodiversity, and (2) plant phylodiversity influences soil microbial productivity. Our data revealed that the gypsophyte Ononis tridentata spatially determines a macrophytic mosaic, ameliorates the microenvironment, and maximizes plant richness and phylodiversity through facilitating non-gypsophyte species. Beyond the direct effect of the nurse plant on soil microbial biomass, activity, and respiration, the analyses suggest a direct effect of plant phylodiversity (MPD) on these general indicators of soil microbial productivity. Plant diversity (Shannon index) neither correlated with the mentioned parameters nor with specific indicators of C, N and P cycling. This is the first report of a relationship between producer phylodiversity and decomposer productivity, which supports phylogenetic diversity as a relevant player of the ecosystem functioning. PMID- 24233689 TI - Synchronizing feather-based measures of corticosterone and carotenoid-dependent signals: what relationships do we expect? AB - Carotenoids produce many of the red, orange and yellow signal traits of birds, and individuals must trade off utilizing carotenoids for physiological processes versus ornamentation. Proximate mechanisms regulating this trade-off are poorly understood, despite their importance for expression of color signals. Corticosterone (CORT) may play a significant mechanistic role in signal expression because it mobilizes energy substrates and influences foraging behavior. We used a unique feather-based approach to test whether CORT mediates expression of carotenoid-based coloration. First, we investigated relationships between levels of CORT from feathers (CORT(f)) and carotenoid-based plumage signals in common redpolls (Acanthis flammea). Then, we determined how the width of growth bars and probability of having fault bars on feathers varied with CORT(f), specifically whether these metrics reflected developmental costs of elevated CORT ("stress" hypothesis) or represented an individual's quality ("quality" hypothesis). CORT(f) correlated positively with the strength of carotenoid signals, but only in adult males. However, also in adult males, CORT(f) was positively related to width of feather growth bars and negatively with probability of having fault bars, providing support for the quality hypothesis. Overall, CORT(f) was lower in adult males than in females or young males, possibly due to dominance patterns. Our results indicate that CORT may indirectly benefit feather quality, potentially by mediating the expression of carotenoid signals. We place our sex-specific findings into a novel framework that proposes that the influences of CORT in mediating carotenoid-based plumage traits will depend on the extent to which carotenoids are traded off between competing functions. PMID- 24233690 TI - Changes in base composition bias of nuclear and mitochondrial genes in lice (Insecta: Psocodea). AB - While it is well known that changes in the general processes of molecular evolution have occurred on a variety of timescales, the mechanisms underlying these changes are less well understood. Parasitic lice ("Phthiraptera") and their close relatives (infraorder Nanopsocetae of the insect order Psocodea) are a group of insects well known for their unusual features of molecular evolution. We examined changes in base composition across parasitic lice and bark lice. We identified substantial differences in percent GC content between the clade comprising parasitic lice plus closely related bark lice (=Nanopsocetae) versus all other bark lice. These changes occurred for both nuclear and mitochondrial protein coding and ribosomal RNA genes, often in the same direction. To evaluate whether correlations in base composition change also occurred within lineages, we used phylogenetically controlled comparisons, and in this case few significant correlations were identified. Examining more constrained sites (first/second codon positions and rRNA) revealed that, in comparison to the other bark lice, the GC content of parasitic lice and close relatives tended towards 50 % either up from less than 50 % GC or down from greater than 50 % GC. In contrast, less constrained sites (third codon positions) in both nuclear and mitochondrial genes showed less of a consistent change of base composition in parasitic lice and very close relatives. We conclude that relaxed selection on this group of insects is a potential explanation of the change in base composition for both mitochondrial and nuclear genes, which could lead to nucleotide frequencies closer to random expectation (i.e., 50 % GC) in the absence of any mutation bias. Evidence suggests this relaxed selection arose once in the non-parasitic common ancestor of Phthiraptera + Nanopsocetae and is not directly related to the evolution of the parasitism in lice. PMID- 24233691 TI - Risk factor of visuospatial neglect: a study of association between visuospatial neglect and anemia. AB - OBJECTIVE: To investigate the correlation between visuospatial neglect and anemia in patients with right cerebral infarction, as well as to identify the risk factor of neglect and furnish preliminary data on rehabilitation management. METHODS: The line bisection test and Albert test were conducted on subjects with right cerebral infarction in order to analyze neglect severity. Multiple linear regression analysis was conducted to investigate correlation between neglect severity and hemoglobin and hematocrit level. Logistic regression analysis was applied to identify the risk factor of neglect. RESULTS: Visuospatial neglect was observed in 33 subjects out of 124. Hemoglobin and hematocrit were not directly correlated with visuospatial neglect severity, whereas infarct size was directly correlated. Subjects with visuospatial neglect were characterized by a large infarct size, a low score in the Mini-Mental State Examination and long hospital stay. CONCLUSION: In this study, visuospatial neglect was found to be uncorrelated with anemia. It implies that emphasis should be placed on the early detection of anemia and neglect in patients with left hemiplegia, the formulation of respective therapeutic plans and improvement of prognosis. The study found that the possibility of a visuospatial neglect occurrence increases with infarct size. In this regard, it is required that visuospatial neglect was detected and treated in the earliest possible stage, notwithstanding the difficulty that lies in the precise measurement of the severity. PMID- 24233692 TI - Time to deal with antibiotics. PMID- 24233697 TI - Ancient DNA. Old dogs teach a new lesson about canine origins. PMID- 24233698 TI - Infectious diseases. Goal of ending AIDS gains traction. PMID- 24233699 TI - Particle physics. Hint of dark matter may be just cosmic ray debris. PMID- 24233700 TI - Genomics. Initiative aims to minister to Mexico's unique genetic heritage. PMID- 24233701 TI - Biomedicine. A putative antiaging drug takes a step from mice to men. PMID- 24233702 TI - The man who bottled evolution. PMID- 24233703 TI - Turning up the light. PMID- 24233704 TI - Biomedical research: strength from diversity. PMID- 24233705 TI - Pest control: embrace marketing. PMID- 24233706 TI - Pest control: biopesticides' potential. PMID- 24233707 TI - Pest control: risks of biochemical pesticides. PMID- 24233709 TI - Conservation. Protected areas and effective biodiversity conservation. PMID- 24233710 TI - Environmental science. What does zero deforestation mean? PMID- 24233711 TI - Climate change. Out of the African Humid Period. PMID- 24233712 TI - Cancer. Potential of the synthetic lethality principle. PMID- 24233713 TI - Chemistry. A nickel finish protects silicon photoanodes for water splitting. PMID- 24233714 TI - Evolution. Transposons up the dosage. PMID- 24233715 TI - Genetics. Can cancer drugs treat immunodeficiency? PMID- 24233716 TI - Ecology. Understanding lakes near and far. PMID- 24233718 TI - Room-temperature quantum bit storage exceeding 39 minutes using ionized donors in silicon-28. AB - Quantum memories capable of storing and retrieving coherent information for extended times at room temperature would enable a host of new technologies. Electron and nuclear spin qubits using shallow neutral donors in semiconductors have been studied extensively but are limited to low temperatures (?10 kelvin); however, the nuclear spins of ionized donors have the potential for high temperature operation. We used optical methods and dynamical decoupling to realize this potential for an ensemble of phosphorous-31 donors in isotopically purified silicon-28 and observed a room-temperature coherence time of over 39 minutes. We further showed that a coherent spin superposition can be cycled from 4.2 kelvin to room temperature and back, and we report a cryogenic coherence time of 3 hours in the same system. PMID- 24233720 TI - Enantioselective Lewis acid catalysis of intramolecular enone [2+2] photocycloaddition reactions. AB - Asymmetric catalysis of photochemical cycloadditions has been limited by the challenge of suppressing the unselective background reaction. Here, we report that the high cross-section pipi* transition of 5,6-dihydro-4-pyridones, a versatile class of enone substrates, undergoes a >50 nanometer (nm) bathochromic absorption shift upon Lewis acid coordination. Based on this observation, enantioselective intramolecular [2+2] photocycloaddition reactions (82 to 90% enantiomeric excess) were achieved with these substrates using 0.5 equivalents of a chiral Lewis acid upon irradiation at a wavelength of 366 nm. One of the products was applied as a key intermediate in the total synthesis of (+)-lupinine and the formal synthesis of (+)-thermopsine. Several enones show similar bathochromic shifts in the presence of a Lewis acid, indicating that chiral Lewis acid catalysis may be a general approach toward enantioselective enone [2+2] photocycloadditions. PMID- 24233719 TI - High-performance silicon photoanodes passivated with ultrathin nickel films for water oxidation. AB - Silicon's sensitivity to corrosion has hindered its use in photoanode applications. We found that deposition of a ~2-nanometer nickel film on n-type silicon (n-Si) with its native oxide affords a high-performance metal-insulator semiconductor photoanode for photoelectrochemical (PEC) water oxidation in both aqueous potassium hydroxide (KOH, pH = 14) and aqueous borate buffer (pH = 9.5) solutions. The Ni film acted as a surface protection layer against corrosion and as a nonprecious metal electrocatalyst for oxygen evolution. In 1 M aqueous KOH, the Ni/n-Si photoanodes exhibited high PEC activity with a low onset potential (~1.07 volts versus reversible hydrogen electrode), high photocurrent density, and durability. The electrode showed no sign of decay after ~80 hours of continuous PEC water oxidation in a mixed lithium borate-potassium borate electrolyte. The high photovoltage was attributed to a high built-in potential in a metal-insulator-semiconductor-like device with an ultrathin, incomplete screening Ni/NiO(x) layer from the electrolyte. PMID- 24233721 TI - Dosage compensation via transposable element mediated rewiring of a regulatory network. AB - Transposable elements (TEs) may contribute to evolutionary innovations through the rewiring of networks by supplying ready-to-use cis regulatory elements. Genes on the Drosophila X chromosome are coordinately regulated by the male specific lethal (MSL) complex to achieve dosage compensation in males. We show that the acquisition of dozens of MSL binding sites on evolutionarily new X chromosomes was facilitated by the independent co-option of a mutant helitron TE that attracts the MSL complex (TE domestication). The recently formed neo-X recruits helitrons that provide dozens of functional, but suboptimal, MSL binding sites, whereas the older XR chromosome has ceased acquisition and appears to have fine tuned the binding affinities of more ancient elements for the MSL complex. Thus, TE-mediated rewiring of regulatory networks through domestication and amplification may be followed by fine-tuning of the cis-regulatory element supplied by the TE and erosion of nonfunctional regions. PMID- 24233722 TI - High-resolution global maps of 21st-century forest cover change. AB - Quantification of global forest change has been lacking despite the recognized importance of forest ecosystem services. In this study, Earth observation satellite data were used to map global forest loss (2.3 million square kilometers) and gain (0.8 million square kilometers) from 2000 to 2012 at a spatial resolution of 30 meters. The tropics were the only climate domain to exhibit a trend, with forest loss increasing by 2101 square kilometers per year. Brazil's well-documented reduction in deforestation was offset by increasing forest loss in Indonesia, Malaysia, Paraguay, Bolivia, Zambia, Angola, and elsewhere. Intensive forestry practiced within subtropical forests resulted in the highest rates of forest change globally. Boreal forest loss due largely to fire and forestry was second to that in the tropics in absolute and proportional terms. These results depict a globally consistent and locally relevant record of forest change. PMID- 24233717 TI - Iron(IV)hydroxide pK(a) and the role of thiolate ligation in C-H bond activation by cytochrome P450. AB - Cytochrome P450 enzymes activate oxygen at heme iron centers to oxidize relatively inert substrate carbon-hydrogen bonds. Cysteine thiolate coordination to iron is posited to increase the pK(a) (where K(a) is the acid dissociation constant) of compound II, an iron(IV)hydroxide complex, correspondingly lowering the one-electron reduction potential of compound I, the active catalytic intermediate, and decreasing the driving force for deleterious auto-oxidation of tyrosine and tryptophan residues in the enzyme's framework. Here, we report on the preparation of an iron(IV)hydroxide complex in a P450 enzyme (CYP158) in >=90% yield. Using rapid mixing technologies in conjunction with Mossbauer, ultraviolet/visible, and x-ray absorption spectroscopies, we determine a pK(a) value for this compound of 11.9. Marcus theory analysis indicates that this elevated pK(a) results in a >10,000-fold reduction in the rate constant for oxidations of the protein framework, making these processes noncompetitive with substrate oxidation. PMID- 24233723 TI - Changes in cytoplasmic volume are sufficient to drive spindle scaling. AB - The mitotic spindle must function in cell types that vary greatly in size, and its dimensions scale with the rapid, reductive cell divisions that accompany early stages of development. The mechanism responsible for this scaling is unclear, because uncoupling cell size from a developmental or cellular context has proven experimentally challenging. We combined microfluidic technology with Xenopus egg extracts to characterize spindle assembly within discrete, geometrically defined volumes of cytoplasm. Reductions in cytoplasmic volume, rather than developmental cues or changes in cell shape, were sufficient to recapitulate spindle scaling observed in Xenopus embryos. Thus, mechanisms extrinsic to the spindle, specifically a limiting pool of cytoplasmic component(s), play a major role in determining spindle size. PMID- 24233724 TI - Cytoplasmic volume modulates spindle size during embryogenesis. AB - Rapid and reductive cell divisions during embryogenesis require that intracellular structures adapt to a wide range of cell sizes. The mitotic spindle presents a central example of this flexibility, scaling with the dimensions of the cell to mediate accurate chromosome segregation. To determine whether spindle size regulation is achieved through a developmental program or is intrinsically specified by cell size or shape, we developed a system to encapsulate cytoplasm from Xenopus eggs and embryos inside cell-like compartments of defined sizes. Spindle size was observed to shrink with decreasing compartment size, similar to what occurs during early embryogenesis, and this scaling trend depended on compartment volume rather than shape. Thus, the amount of cytoplasmic material provides a mechanism for regulating the size of intracellular structures. PMID- 24233725 TI - Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death. AB - Bacterial invasion of host tissues triggers polymorphonuclear leukocytes to release DNA [neutrophil extracellular traps (NETs)], thereby immobilizing microbes for subsequent clearance by innate defenses including macrophage phagocytosis. We report here that Staphylococcus aureus escapes these defenses by converting NETs to deoxyadenosine, which triggers the caspase-3-mediated death of immune cells. Conversion of NETs to deoxyadenosine requires two enzymes, nuclease and adenosine synthase, that are secreted by S. aureus and are necessary for the exclusion of macrophages from staphylococcal abscesses. Thus, the pathogenesis of S. aureus infections has evolved to anticipate host defenses and to repurpose them for the destruction of the immune system. PMID- 24233726 TI - Complete mitochondrial genomes of ancient canids suggest a European origin of domestic dogs. AB - The geographic and temporal origins of the domestic dog remain controversial, as genetic data suggest a domestication process in East Asia beginning 15,000 years ago, whereas the oldest doglike fossils are found in Europe and Siberia and date to >30,000 years ago. We analyzed the mitochondrial genomes of 18 prehistoric canids from Eurasia and the New World, along with a comprehensive panel of modern dogs and wolves. The mitochondrial genomes of all modern dogs are phylogenetically most closely related to either ancient or modern canids of Europe. Molecular dating suggests an onset of domestication there 18,800 to 32,100 years ago. These findings imply that domestic dogs are the culmination of a process that initiated with European hunter-gatherers and the canids with whom they interacted. PMID- 24233727 TI - The consequence of tree pests and diseases for ecosystem services. AB - Trees and forests provide a wide variety of ecosystem services in addition to timber, food, and other provisioning services. New approaches to pest and disease management are needed that take into account these multiple services and the different stakeholders they benefit, as well as the likelihood of greater threats in the future resulting from globalization and climate change. These considerations will affect priorities for both basic and applied research and how trade and phytosanitary regulations are formulated. PMID- 24233728 TI - The cytoskeleton of Cobaea seed hairs: : Patterning during cell-wall differentiation. AB - The cell wall of Cobaea scandens seed hairs developed in a characteristic sequence, with the deposition of a cellulose thread onto a pectic swelling layer was the final event. The cellulose thread was intracellularly accompanied by a band of 10-18 microtubules. During the formation of the swelling layer the microtubules were homogeneously distributed; they ran circumferentially normal to the cell axis. When cellulose-thread formation started, the microtubules became arranged in a helical band. The density of the microtubules varied during the different phases of development. The highest density was observed before cellulosethread formation and ranged from 6-15 MUm.MUm(-2). The length of the microtubules, 20-30 MUm, was determined by direct measurements, as well as estimated from the total microtubular length in a given area and the counted free ends. With the indirect immunofluorescence technique the microtubules of the band stained inhomogeneously. Those which were located at the edges of the band fluoresced more intensely than those of the central part. Attempts to visualize actin filaments in the hair cells with rhodaminyl-conjugated phalloidin resulted in a homogeneous staining of the area of the microtubular band, indicating that actin filaments may be present in this region. Though, in thin sections and dry cleaved cells, filamentous structures were observed between the microtubules, caution is expressed that the observed fluorescence was, indeed, due to actin filaments. The role of the filamentous structures is discussed with respect to formation and maintenance of the microtubular band. Microtubules apparently did not cross coated pits which were visualized in the plasma membrane through the dry-cleaving technique. PMID- 24233729 TI - Pollen wall formation in Lilium: The effect of chaotropic agents, and the organisation of the microtubular cytoskeleton during pattern development. AB - Using a combination of electron-microscopic and immunocytochemical techniques the behaviour of the microtubular cytoskeleton has been followed throughout microsporogenesis in Lilium henryi Thunb. Cells treated with colchicine at specific stages and then permitted to develop to near maturity were used to investigate any participation by microtubules in the regulation of pollen wall patterning. The microtubular cytoskeleton assumes four principal forms during the meiotic process; in pre-meiosis it resembles that characteristic of meristematic somatic cells, during meiotic prophase it becomes associated with a nuclear envelope and, perhaps, with the chromosomes and, as the nuclear and cell divisions commence, it takes the form of a normal spindle apparatus. In the young microspores, microtubules assume a radial organisation extending from sites at the nuclear envelope to the inner face of the plasma membrane. No firm evidence was found linking any one of these forms of cytoskeleton with the generation of patterning on the cell surface. Experiments with colchicine revealed that the drug would readily dislocate the colpus, but did not affect the general reticulate patterning. The radial cytoskeleton was present during the deposition of the early primexine, but evidence from these and other studies (J.M. Sheldon and H.G. Dickinson 1983, J. Cell. Sci. 63, 191-208; H.G. Dickinson and J.M. Sheldon, 1984, Planta 161, 86-90) indicates patterning to be imprinted upon the plasma membrane prior to the appearance of this type of cytoskeleton. These results are discussed in terms of a recent model proposed to explain pattern generation on the surface of Lilium pollen grains, based on the "self-assembly" of patterning determinants within the plasma membrane. PMID- 24233730 TI - Characteristic symptoms of photosynthesis inhibition by herbicides are expressed in photomixotrophic tissue cultures of Nicotiana. AB - A photomixotrophic tissue culture system for Nicotiana plumbaginifolia and N. tabacum has been developed in which a primary symptom (bleching) of the inhibition of photosynthetic electron transport by herbicides can be observed. Photomixotrophic cultures were initiated and maintained in the light on medium containing 0.2-0.3% sucrose or glucose (low-sugar medium) as sole source of respirable carbohydrate. The usual medium for growing heterotrophic cultures contains 2-3% sucrose or glucose (high-sugar medium). Callus grown on low-sugar medium achieved a fresh weight three to four times greater in the light than in the dark and reached about half that of callus grown on high-sugar medium. Carbon dioxide fixation rates were an order of magnitude higher in cultures grown on low sugar medium in the light than in those grown on high-sugar medium or in any of the dark-grown cultures. The lightdependent growth and CO2-fixation rates of cultures grown on low-sugar medium indicated that a major proportion of the weight increase resulted from photosynthesis. Under these photomixotrophic conditions it was found that a number of photosystem-II herbicides, at concentrations which inhibit photosynthetic electron transport, also inhibited the light-dependent component of callus growth, and caused bleaching. These effects could not be demonstrated on high-sugar medium. PMID- 24233731 TI - Transplantation of isolated nuclei into plant protoplasts : A novel technique for introducing foreign DNA into plant cells. AB - The uptake of isolated nuclei from Vicia hajastana Grossh. cells into protoplasts of an auxotrophic cell line of Datura innoxia P. Mill. was induced under the influence of polyethylene glycol and Ca(2+) at pH 6.8. The frequency of nuclear uptake varied from 0.8 to 2.3% and that of the recovery of prototrophic clones from 10(-5) to 6.10(-4). The prototrophic nuclear fusion products following nuclear uptake could be rescued by initial culture of the protoplasts in non selective conditions and by the subsequent use of feeder cell layers to support the growth of surviving colonies on a selective medium. The presence of Vicia genomic DNA in some prototrophic clones was confirmed by dot-blot hybridization using Datura and Vicia DNA probes. In certain transformed clones, the recovery of prototrophy was accompanied by the restoration of morphogenetic potential. Welldeveloped shoots typical of wild-type Datura could be regenerated employing an appropriate regeneration medium. PMID- 24233732 TI - Graphical evaluation and partitioning of turgor responses to drought in leaves of durum wheat. AB - The relationship between relative water content (R) and turgor potential (Psip) may be derived from pressure-volume (PV) curves and analyzed in various ways. Fifty PV curves were measured with the pressure chamber on leaves of durum wheat (Triticum durum L.). The plots of Psip versus R were highly variable and could not be adequately described by a single mathematical function. The area below the curve was therefore determined by means of an area meter. This procedure gave the integral of turgor from full saturation to the turgor-loss point. Responses to drought treatment could thus be quantified and partitioned into effects of osmotic adjustment and elastic adjustment. These two adjustment responses, which are probably of different metabolic origin, together improve turgor maintenance in durum wheat considerably. PMID- 24233733 TI - Morphogenetic factors controlling differentiation and dedifferentiation of epidermal cells in the gynoecium of Catharanthus roseus : II. Diffusible morphogens. AB - During postgenital fusion of the distal adaxial surfaces of the two originally separate carpel primordia of Catharanthus roseus (L.) G. Don, approx. 400 epidermal cells undergo rapid dedifferentiation into parenchymatous cells. To characterize the mechanism of the induction of dedifferentiation, various types of both water-permeable and water-impermeable barriers were placed between pre fusion carpels. Barriers which did not allow the passage of water-soluble agents blocked dedifferentiation. Barriers which allowed passage of water-soluble agents did not block dedifferentiation of the contacting epidermal cells, implicating a diffusible agent or "morphogen" as the factor responsible for dedifferentiation. Experiments with barriers of known pore size demonstrated that the molecular weight of this morphogen was less than 1000. The two cell walls and thin cuticle present at the site of this postgenital fusion do not block the movement of some substances between the fusing carpels. Tracer studies with tritium-labeled asparagine confirmed that substances can be transported across the fusion plane. PMID- 24233734 TI - Salt treatment induces frost hardiness in leaves and isolated thylakoids from spinach. AB - Frost hardiness of spinach (Spinacia oleracea L.) leaves was increased by high concentrations of NaCl in the hydroponic culture medium. Freezing damage was determined by measurement of slow chlorophyll fluorescence quenching after freezing of leaves. Both the osmolality of the leaf sap and forst hardiness of the leaves were linearly correlated with the salt concentration in the hydroponic culture medium. Freezing damage occurred, irrespective of the extent of frost hardening, when dehydration of cells during extracellular ice formation decreased cellular volume to approximately 14% of the volume of unfrozen cells. The resistance of isolated, washed thylakoids against mechanical and chemical damage by freezing was investigated. Chemical damage by freezing caused by salt accumulation was measured as release of chloroplast coupling factor (CF1; EC 3.6.1.3), and mechanical damage was measured as release of the lumenal protein plastocyanin from the membranes during an in-vitro freeze-thaw cycle. Isolated thylakoids from salt-treated frost-hardy spinach and those from plants hardened under natural conditions did not exhibit improved tolerance against chemical freezing stress exerted by high salt concentrations. They were, however, more hardy than thylakoids from unhardened control leaves against mechanical damage by freezing. PMID- 24233735 TI - Are carotenoids the blue-light photoreceptor in the photoinduction of protoperithecia in Neurospora crassa? AB - A triple albino mutant of Neurospora crassa with a measured content of carotenoids absorbing at 470 nm less than 0.5% of that of the wild type (calculated value less than 8.10(-4)%) had the same threshold for photoinduction of protoperithecia as the wild type when illuminated with monochromatic light at 471 nm. This is strong evidence against the hypothesis that the bulk of carotenoids are the blue-light photoreceptor for this phenomenon. However, it is impossible to exclude traces of carotenoids acting as the photoreceptor at less than 3.10(-12) M in a very efficient sensory transduction chain. PMID- 24233736 TI - Ethylene production and beta-cyanoalanine synthase activity in carnation flowers. AB - The relationship between ethylene production and the CN(-)-assimilating enzyme beta-cyanoalanine synthase (CAS; EC 4.4.1.9) was examined in the carnation (Dianthus caryophyllus L.) flower. In petals from cut flowers aged naturally or treated with ethylene to accelerate senescence the several hundred-fold increase in ethylene production which occurred during irreversible wilting was accompanied by a one- to twofold increase in CAS activity. The basal parts of the petal, which produced the most ethylene, had the highest CAS activity. Studies of flower parts (styles, ovaries, receptacles, petals) showed that the styles had a high level of CAS together with the ethylene-forming enzyme (EFE) system for converting 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene. The close association between CAS and EFE found in styles could also be observed in detached petals after induction by ACC or ethylene. Treatment of the cut flowers with cycloheximide reduced synthesis of CAS and EFE. The data indicate that CAS and ethylene production are associated, and are discussed in relation to the hypothesis that CN(-) is formed during the conversion of ACC to ethylene. PMID- 24233737 TI - Simulation of in situ freezing damage of the photosynthetic apparatus by freezing in vitro of thylakoids suspended in complex media. AB - Chloroplast thylakoid membranes were isolated from leaves of unhardened and cold acclimated spinach (Spinacia oleracea L.). For freezethaw treatment, the membranes were suspended in complex media composed to simulate the solute concentrations in the chloroplast stroma in the unhardened and hardened states of the leaves. In particular, high concentrations of amino acids were applied for simulating the hardened state. After frost treatment, photosynthetic activities and chlorophyll fluorescence parameters of the thylakoids were tested to determine the degree of freezing damage. The results revealed a pattern of freezing injury similar to that observed upon frost treatment of thylakoids in situ. A major manifestation of damage was the inhibition of photosynthetic electron transport. Uncoupling of photophosphorylation, which is the dominating effect of freezing of thylakoids suspended in binary solutions (e.g., containing one sugar and one inorganic salt), was also visible but less pronounced in the complex media. Thylakoids obtained from cold-acclimated leaves did not exhibit an increased frost tolerance in vitro, as compared with thylakoids from unhardened plants. The results, furthermore, indicated a strong protective effect of free amino acids at the concentrations and composition found in chloroplasts of hardened leaves. The presence of inorganic salts in the complex media slightly stabilized rather than damaged the membranes during freezing. It is concluded that inactivation of thylakoids in situ may be understood as the destabilizing action of the combined solutes surrounding the thylakoids, occurring when solute concentration is raised due to freezing of water. PMID- 24233738 TI - Amylolytic activity in germinated Agrostemma githago L. seeds. AB - The perisperm of seeds of Agrostemma githago contains starch reserves which constitute 40% of the dry weight of the mature seed. These starch reserves were mostly broken down between 48 and 96 h after initiation of imbibition. (Germination occurred after 24 h.) The mode of starch degradation showed close parallels with the breakdown of the starchy endosperm in cereals. Thus, between 24 and 96 h the cotyledons secreted alpha-amylase (EC 3.2.1.1) whereas other degradative enzymes in the perisperm, beta-amylase (EC 3.2.1.2) and maltase (EC 3.2.1.20), appeared to originate in the perisperm itself. Cotyledons secreted similar levels of alpha-amylase in the presence and absence of exogenous starch, indicating that secretion is an internal developmental event of the embryo. By isoelectric focussing the secreted alpha-amylase was separated into two isoenzymes. In the cotyledons, several other starch-degrading isoenzymes were present but were not secreted. PMID- 24233739 TI - Stimulation of photosynthesis by 2% oxygen at low temperatures is restored by phosphate. AB - The effect of phosphate feeding on the influence of low (2%) oxygen on photosynthetic carbon assimilation has been investigated in leaf discs of spinach (Spinacia oleracea L.) at 12 degrees C. The following observations were made. First, after the transition from 20% O2 to 2% O2, the rate of CO2 uptake was inhibited at CO2 concentrations between about 250 and about 800 MUl CO2.l(-1). Second, phosphate feeding stimulated the rate of CO2 uptake in 20% O2 at higher concentrations of CO2 (500-900 MUl.l(-1)). Third, phosphate feeding stimulated the rate of CO2 uptake in 2% O2 at all but the highest (900 MUl.l(-1)) and lowest 74 (MUl.l(-1)) concentrations of CO2 employed. Phosphate thereby restored the stimulation of photosynthesis by 2% O2 and it did so over a wide range of lower temperatures. Fourth, oscillatory behaviour, however generated, was dampened by phosphate feeding, even at very low concentrations of CO2. Contents of leaf metabolites were measured during the transition to 2% O2 in control and phosphate fed leaf discs. During this period the ratio glycerate-3-phosphate/triose phosphate rose steeply, but fell again only in the phosphate-treated leaf discs. These data, taken together with measured ATP/ADP ratios, showed that assimilatory power, the ratio [ATP].[NAD(P)H]/[ADP].[Pi].[NAD(P)], decreased when leaves were exposed to 2% O2, but that this decrease was minimised by previous feeding of phosphate. The mechanism of phosphate limitation is discussed in the light of the results. PMID- 24233740 TI - Rapid appearance of an mRNA correlated with ethylene synthesis encoding a protein ofmolecular weight 35000. AB - Changes in gene expression related to ethylene synthesis were investigated during ripening of tomato fruit, and in unripe fruit and leaves after wounding. Messenger RNA was extracted at different stages of ripening, or at various times after wounding, and translated in vitro. A number of changes in mRNA were noted in all cases, including an increase in one encoding a protein of MW 35000. The mRNA encoding this protein in ripening fruit was hybrid-selected by a ripening related complementary DNA clone, pTOM13. This clone also selected an mRNA encoding a protein of MW 35000 from RNA extracted from wounded unripe fruit and wounded leaves, but not from unwounded control tissue. During ripening and after wounding the appearance of mRNA for the MW-35000 protein was correlated with increased ethylene synthesis. In unripe fruit, the increase in mRNA for the MW 35000 protein and in ethylene synthesis were detected within 30 min of wounding. In-vivo labelling showed that a protein of MW 35000 was also synthesised rapidly in wounded fruit tissue. We suggest that the mRNAs encoding the MW-35000 proteins that increased during ripening and in response to wounding are the same and may be related to ethylene synthesis. PMID- 24233741 TI - Cell-cycle arrest of plant suspension cultures by tunicamycin. AB - The effect of tunicamycin, an inhibitor of N-glycosylation of proteins, on growth and on synthesis of DNA and protein was studied in suspension cultures from Nicotiana tabacum and Catharanthus rosea. In the presence of 0.1-1 MUg . ml(-1) tunicamycin, cell division and DNA synthesis stopped in cells which had been proliferating logarithmically, but protein formation continued. Cytophotometric determination of the nuclear DNA content in Catharanthus cells showed that a cell cycle arrest had occurred in G1 phase. Metabolic labelling of cells with the glycoprotein precursors glucosamine or mannose was inhibited, too. The results indicate that one or more glycoproteins are needed for the cell to pass through the G1 phase, as was recently postulated for animal and yeast cells. PMID- 24233742 TI - TL-DNA from Agrobacterium rhizogenes plasmid pRi1855 reduces the osmotic pressure in transformed plants grown in vitro. AB - Growth, water content, osmotic pressure and solute content were examined for normal potato (Solanum tuberosum L. cv. Desiree) and a derivative (line D9X8a), which was genetically transformed with TL-DNA from Agrobacterium rhizogenes. Plants were grown (i) in vitro, (ii) in a growth chamber and (iii) in the field. In vitro, the transformed potato plants produced more biomass than the untransformed plants, partly because they had a higher water content. Potassium concentration and osmotic pressure were lower in cell sap extracted from the transformed potato shoots. In some cases the difference was as much as 50%. These differences were less clear, absent or reversed in plants from a growth chamber or from the field. In the field, however, transformed potato senesced early. It is suggested that a cellular basis for these observations may be changes induced by Ri TL-DNA expression products in plant membrane properties. PMID- 24233744 TI - Gibberellins in dark- and red-light-grown shoots of dwarf and tall cultivars of Pisum sativum: The quantification, metabolism and biological activity of gibberellins in Progress no. 9 and Alaska. AB - The stem growth in darkness or in continuous red light of two pea cultivars, Alaska (Le Le, tall) and Progress No. 9 (le le, dwarf), was measured for 13 d. The lengths of the first three internodes in dark-grown seedlings of the two cultivars were similar, substantiating previous literature reports that Progress No. 9 has a tall phenotype in the dark. The biological activity of gibberellin A20 (GA20), which is normally inactive in le le geno-types, was compared in darkness and in red light. Alaska seedlings, regardless of growing conditions, responded to GA20. Dark-grown seedlings of Progress No. 9 also responded to GA20, although red-light-grown seedlings did not. Gibberellin A1 was active in both cultivars, in both darkness and red light. The metabolism of [(13)C(3)H]GA20 has also been studied. In dark-grown shoots of Alaska and Progress No. 9 [(13)C(3)H]GA20 is converted to [(13)C(3)H]GA1, [(13)C(3)H]GA8, [(13)C]GA29, its 2alpha-epimer, and [(13)C(3)H]GA29-catabolite. [(13)C(3)H] Gibberellin A1 was a minor product which appeared to be rapidly turned over, so that in some feeds only its metabolite, [(13)C(3)H]GA8, was detected. However results do indicate that the tall growth habit of Progress No. 9 in the dark, and its ability to respond to GA20 in the dark may be related to its capacity to 3beta-hydroxylate GA20 to give GA1. In red light the overall metabolism of [(13)C(3)H]GA20 was reduced in both cultivars. There is some evidence that 3beta-hydroxylation of [(13)C(3)H]GA20 can occur in red light-grown Alaska seedlings, but no 3beta hydroxylated metabolites of [(13)C(3)H]GA20 were observed in red light-grown Progress. Thus the dwarf habit of Progress No. 9 in red light and its inability to respond to GA20 may be related, as in other dwarf genotypes, to its inability to 3beta-hydroxylate GA20 to GA1. However identification and quantification of native GAs in both cultivars showed that red-light-grown Progress does contain native GA1. Thus the inability of red light-grown Progress No. 9 seedlings to respond to, and to 3beta-hydroxylate, applied GA20 may be due to an effect of red light on uptake and compartmentation of GAs. PMID- 24233743 TI - Isolation and characterization of glycoprotein lectins from the bark of three species of elder, Sambucus ebulus, S. nigra and S. racemosa. AB - Lectins have been isolated from the bark of three members of the family Caprifoliaceae, Sambucus nigra (elder), S. racemosa (red-berried elder) and S. ebulus (dwarf elder), by affinity chromatography on fetuin-agarose, ion-exchange and gel-filtration chromatography. They are all glycoproteins of M r 140 000 made up of at least four subunits. The lectin have similar but not identical amino acid compositions and the carbohydrate content varies between 12% and 19% (w/w), the main sugars being (N-acetyl)glucosamine, mannose, fucose and xylose. Inhibition studies of hemagglutination with various mono- and oligosaccharides have shown that N-acetylgalactosamine and galactose together with galactose containing oligosaccharides are the most effective inhibitors. There are some differences in specificity, in particular S. ebulus agglutinin is inhibited to the same degree by galactosamine, N-acetylgalactosamine and by galactose. PMID- 24233745 TI - Alcohol dehydrogenase activity in the roots of marsh plants in naturally waterlogged soils. AB - The aim of this work was to discover whether oxygen tensions in the roots of marsh plants in flooded soils are high enough to allow fully acrobic metabolism. Activity of alcohol dehydrogenase (ADH), a protein synthesised in anoxic plants, was measured in roots of marsh plants growing in habitats where the availability of oxygen to the roots would be expected to differ. Roots of Carex riparia in standing water had ADH activities about 2.5 times higher than those of phosphofructokinase, and comparable to ADH activities of Poa trivialis, Urtica dioica and Ranunculus repens roots in dry soil. Removal of the oxygen supply via aerenchyma to Carex roots caused a 30-fold increase in ADH activity relative to that of phosphofructokinase. There was no change in ADH activity with depth in Carex roots in waterlogged soil, but in Filipendula ulmaria roots activity was 14 times higher below 10 cm depth than near the surface. Urtica roots in waterlogged soil had alcohol dehydrogenase activities 26 times higher than roots in dry soil, but for Poa and Ranunculus roots this figure was only 1.7 and 4.2, respectively. These results indicate that the oxygen tensions in the roots of marsh plants in waterlogged soil differ considerably among species. Ethanol was the major product of fermentation in roots of all species studied. There was no correlation between ADH activity and the rate of ethanol production under anoxia of Urtica roots. The physiological significance of high ADH activities in roots is thus unclear. PMID- 24233746 TI - Hexose-transport-deficient mutants of Chlorella vulgaris : Lack of transport activity correlates with absence of inducible proteins. AB - Autotrophically grown cells of Chlorella vulgaris show a strong increase in the uptake rates for hexoses and for seven amino acids when incubated in the presence of hexoses. This increase is due to de-novo synthesis of three transport proteins: one forhexoses and two for amino acids. Mutants deficient in hexose transport were obtained after treatment of wild-type cells with acridine orange, followed by a selection procedure using the toxic hexose analogue, 2-deoxy-D glucose. Moreover, the two amino-acid-transport systems could not be induced in these mutants by hexoses. The capacity to phosphorylate hexoses was identical in mutants and in the wild-type strain. The loss of transport activities can be correlated with the loss of certain radiolabeled protein bands on fluorograms of sodium dodecylsulfate-polyacrylamide gels. These proteins are assumed to be responsible for the different transport systems in the wild-type strain. With the help of additional mutants defective in one or two of the different aminoacid transport systems, it has been attempted to assign the different transport activities to individual protein bands on the gel. PMID- 24233748 TI - Deposition and storage of solid-bound heavy metals in the floodplains of the River Geul (the Netherlands). AB - Because of past mining activities, the floodplains of the River Geul are polluted with heavy metals. The continuous supply of fresh sediments during floods has caused the floodplain soils to exhibit large quality variations in time. By measurements of (137)Cs deposition rates in part of the floodplain area were determined at 0.4 to 2.7 cm yr(-1). Analysis of soil metal concentrations at various depths at 65 locations, revealed that the upper 40 cm of the soil profile deposited during the past 30-45 yr, exhibit the highest metal levels. The geostatistical interpolation technique kriging was used to map actual and past pollution patterns. It was shown that, as a result of variable deposition rates, the spatial correlation structure of soil metal concentrations becomes less clear with increasing depth/age. Kriged maps of average metal concentrations in the upper 100 cm of the soil profile provided the basis for the calculation of the mass storage of heavy metals. PMID- 24233749 TI - Trace elements and organochlorines in surf scoters from San Francisco Bay, 1985. AB - Surf scoters (Melanitta perspicillata) were collected from 6 locations in San Francisco Bay during January and March 1985. Overall, mean concentrations of cadmium and zinc were higher in livers of scoters from the southern region of the Bay, whereas mean iron and lead were higher in those from the northern Bay region. Mean concentrations of arsenic, copper, lead, zinc, aluminum (January only) and iron (January) also differed among individual locations. Mean concentrations of copper and zinc increased, arsenic decreased, and cadmium remained the same between January and March. Selenium and mercury concentrations in scoter livers were not significantly correlated (P>0.05), but cadmium concentrations in livers and kidneys were positively correlated (P<0.0001), and body weight was negatively related to mercury concentration in the liver (P<0.05). Body weight differed among locations but not between January and March. Body weight was correlated with lipid content (P<0.0001). DDE and PCBs were each detected in 34 of 36 scoter carcasses. DDE increased significantly between January and March at Richmond Harbor, but BCBs did not differ between January and March at the 3 locations that could be tested. PMID- 24233750 TI - A method for characterising natural and waste waters using plant seeds. AB - Studies were conducted to describe a method for the characterisation of natural and waste waters using plant seed germination as a technique for toxicity testing. Maize seeds were found to be more sensitive to differences in water quality than cowpea seeds and also showed more consistency in results. Trials conducted using natural waters and effluents from gold mining and textile manufacturing operations are also reported. PMID- 24233751 TI - Spatial patterns in forest composition and standing dead red spruce in montane forests of the Adirondacks and northern Appalachians. AB - The decline of red spruce (Picea rubens Sarg.) in montane forests of the northeastern United States has been previously reported. The objective of this study was to assess spatial patterns, if any, in standing dead red spruce stems in the Adirondacks of New York and northern Appalachians of Vermont, New Hampshire, and Maine. A stratified random sample of 19 mountains along a west to east transect in the Adirondacks and the northern Appalachians showed that the live basal area of all species was highest in the White Mountains (34.6 m(2) ha( 1)) and lowest in the Adirondack Mountains (23.7 m(2) ha(-1)) in the Green Mountains was significantly lower than in any other region. Intact standing dead red spruce in the Adirondack and Green Mountains (30%) was significantly higher than that in the three eastern clusters (14%). The amount of intact standing dead red spruce trees increased with elevation in only the western part of the region. With the exception of the Adirondacks, there was a greater average percent dead red spruce on the west side than on the east side of each mountain. The sum of standing dead for other tree species (average 13%) showed no statistically significant patterns with region, elevation or aspect, and was significantly lower than the amount of total dead red spruce (average 42%). The standing dead red spruce patterns we observed cannot be associated with any specific causal factors at this time. PMID- 24233752 TI - Effects of additives on solidification of API separator sludge. AB - API separator sludge was solidified with various combinations of binders and absorbent soil additives. The binders utilized were Type I Portland Cement, Type C Flyash, and a 1:1 combination of the two. The soil additives used were bentonite, diatomite, Fuller's earth, and two brands of chemically altered bentonites, or organoclays. The effectiveness of the solidification materials was based on their effect on the physical and leaching characteristics of the sludge.It was determined the Portland cement and combination binders provided the sludge with adequate physical and strength characteristics. It was also determined the affinity of each additive for water had an important influence on the physical characteristics of the solidified sludge. The results of the leaching procedure indicated the binders alone reduced the leachability of organic constituents from the sludge by 1/5 to 1/10. It appeared the use of the additives with the binders may have further reduced the leachability of constituents from sludge, with the incorporation of the organoclay additives further reducing leachability by up to 1/2. Also, it appeared the absorbing capacity of the additives was directly related to their ability to reduce the leachability of organic constituents from the sludge. PMID- 24233754 TI - Language-learning disabilities: Paradigms for the nineties. AB - We are beginning a decade, during which many traditional paradigms in education, special education, and speech-language pathology will undergo change. Among paradigms considered promising for speech-language pathology in the schools are collaborative language intervention and strategy training for language and communication. This presentation introduces management models for developing a collaborative language intervention process, among them the Deming Management Method for Total Quality (TQ) (Deming 1986). Implementation models for language assessment and IEP planning and multicultural issues are also introduced (Damico and Nye 1990; Secord and Wiig in press). While attention to processes involved in developing and implementing collaborative language intervention is paramount, content should not be neglected. To this end, strategy training for language and communication is introduced as a viable paradigm. Macro- and micro-level process models for strategy training are featured and general issues are discussed (Ellis, Deshler, and Schumaker 1989; Swanson 1989; Wiig 1989). PMID- 24233755 TI - Developmental dyslexia revisited and projected. AB - There are three parts to this paper. First, I review briefly the signposts from research, theory, and application in developmental dyslexia in the 1960s and the 1970s that have led us from there to here, and show the pitfalls to avoid. Second, I discuss some of the pertinent issues of the 1980s: the role of intelligence in the diagnosis of children with specific reading disabilities, the distribution of reading difficulties and disabilities, and the important place of verbal efficiency. Third, I project to the 1990s to emphasize the challenge of the computer technology as mediated learning and the challenge of "bounded rationality" and "collective rationality" in education. Throughout this survey, the paramount role of knowledgeable and caring teachers is implicit. PMID- 24233756 TI - The structured flexibility of Orton-Gillingham. AB - This paper discusses a philosophic basis for Orton-Gillingham teaching and attempts to demonstrate how certain of the features of such multisensory teaching act to remediate language problems exhibited by many dyslexic students. The common basis of the array of programs coming from both Orton and Gillingham is addressed. Some individual strengths and minor differences between Orton and Gillingham variations are examined. PMID- 24233757 TI - Early language intervention: A deterrent to reading disability. AB - Reading is a language art! In acquiring competence in reading we build on proficiencies already available in the primary (spoken) language system. Language is made up of three primary components that impact on reading-phonology, or the sound structure of language including syllables and phonemes; syntax, or the rules governing the sequential ordering of words in phrases and sentences; and semantics, or the meaning system that is attached to words and phrases as a consequence of experiences in a variety of contexts. All three depend upon adequate short- and long-term memory capacities and functioning for their growth and refinement. Additionally, the bridging of speech to print, or the task of establishing sound/symbol correspondences in beginning reading draws not only upon phonological competencies and memory, it is also dependent upon the discovery that words are made up of smaller and isolable parts. This knowledge is often referred to as auditory segmenting which is one aspect of metalinguistic awareness.This paper will discuss these five language roots of reading. The authors will report on research that demonstrates that children, upon school entrance, do not all possess equal levels of competencies in these five critical language areas. Since success in beginning reading is dependent upon the adequate development and functioning of each of the five language areas noted above, early school experiences should be directed toward language development, as well as reading instruction, if we are to reduce the incidence of reading difficulties in our schools. Finally, we will offer suggestions for enhancing language competencies that will support and promote the acquisition of reading. PMID- 24233758 TI - Teachers' opinions of the whole language approach to reading instruction. AB - This article reports the findings of a study of the opinions of first- and first/second-grade teachers of certain comments made about the whole language approach to reading instruction by leading advocates of this procedure. The investigation revealed that these teachers rejected as "false" more of these comments about the whole language approach than they accepted as "true." The findings of this study, apparently the first of their kind that have been reported, suggest that less progress has been made in persuading teachers that the whole language approach to reading instruction is the preferred teaching procedure than some leaders of the whole language movement previously have claimed. PMID- 24233759 TI - Use of an orton-gillingham approach to teach a foreign language to dyslexic/learning-disabled students: Explicit teaching of phonology in a second language. AB - Recent research findings suggest that students who have difficulty learning a second language have weaknesses in oral and written native-language skills which affect their performance in the foreign-language classroom. These weaknesses involve understanding the phonological, syntactic, and semantic codes of language. Evidence suggests that dyslexic/learning-disabled and other "at risk" students who struggle in the second language classroom exhibit particular difficulty with the phonological and syntactic codes of the language. The Orton Gillingham method, a multisensory, structured language approach which adheres to the direct and explicit teaching of phonology, is presented as an alternative to the "natural" communication approaches recently developed by foreign-language educators to teach a second language. A method for adapting this approach for teaching Spanish is described. PMID- 24233760 TI - Reading program-Remedial, integrated, and innovative. AB - An innovative integrated remedial reading program has been developed based on recent research findings. My longitudinal studies have revealed that poor reading compounds itself over the years. The majority of children with reading disabilities currently remain in regular classrooms with varying techniques being used depending upon individual school directives and current educational theory.Despite current remedial techniques, the poorer reader tends to remain so throughout the school years. Innovative techniques must be developed in the hope of altering this pattern.This paper presents one alternative strategy which can be used to upgrade reading skills and break the cycle of reading failure. The Reading Assistance Tutorial Pack (R.A.T. Pack) is a carefully sequenced series of activities that enables the learner to experience the motivating and reinforcing properties of success through all stages of phonetic and reading skills development.It is a systematic, multidisciplinary remedial reading program based on sound behavior, psycholinguistic and cognitive theories of learning incorporating listening, speaking, seeing, writing, thinking, and comprehension skills. The R.A.T. Pack demands a high percentage of on-task behavior and trains phonological processing strategies. Functional language use is promoted through enjoyable activities involving sentence construction, cloze passages, puzzles, games, and other creative manipulations of the surface features of languages. The program has proven successful in schools, homes, and clinics. PMID- 24233761 TI - Nonverbal learning disabilities and remedial interventions. AB - Adolescents with nonverbal learning disabilities who enroll in private, special secondary schools consistently present a pattern of behaviors which prevents achievement of their potentials in academic areas and impedes their abilities to interact effectively with others. With weaknesses in the fine graphomotor skills for writing and poor organization at all levels, they produce limited written output and often fail to complete academic assignments. Their response to pressure to produce is to become less productive. These students perceive social situations inaccurately; they are not successful in their interactions, especially with peers. They have learned to resolve difficult situations by employing their relatively strong verbal skills to enlist parents and other adults in intervening for them. They have not developed the skills to intervene for themselves.Effective remedial interventions include training the students in skills for planning and organizing, for studying, for written expression, and in social cognition and interpersonal communication. Students gain positive feelings of personal effectiveness through a process-at first verbally mediated, ultimately verbally self-directed-in which they are encouraged to plan, risk, and act on their own behalfs to resolve matters of personal concern. PMID- 24233762 TI - Spelling errors and reading fluency in compensated adult dyslexics. AB - Generally, a person who is diagnosed as dyslexic remains diagnosably dyslexic all his/her life. However, occasionally, an individual compensates for his/her difficulties in some way, and by adulthood is no longer diagnosably dyslexic. In what ways are these compensated dyslexics different from both dyslexics and nondyslexics? We compared IQ, achievement test, and spelling error scores in adult dyslexics, adult nondyslexics, and adult compensated dyslexics (N=25) in the two studies reported here. The second study differed from the first in that the subjects were matched for age, education, IQ, and SES. In both studies, compensateds were significantly different from nondyslexics on the WRAT Spelling subtest and Reading Quotient scores. In the second study the compensateds differed from the nondyslexics in total raw score and average reading speed on Gray Oral Reading Test. On the other hand, they were different from dyslexics on all reading and spelling variables in both studies, except for PIAT Reading Comprehension in Study 2. Finally, in Study 2, the compensateds were different from both dyslexics and nondyslexics in average reading speed. In conclusion, it appears that compensation does not result from differences in IQ, education, or SES, though it may be influenced to some extent by sex. Compensateds appear very similar to nondyslexics in their reading and spelling skills; however, there appears to be a difference in the automaticity with which they apply these skills. PMID- 24233763 TI - Early identification of dyslexia: Evidence from a follow-up study of speech language impaired children. AB - A group of speech-language impaired children was administered a battery of standardized language tests and measures of phonological processing in kindergarten. Performance on these language measures was then compared to reading ability in first grade. Results indicated that children with semantic-syntactic language deficits had more difficulties in reading than did children with primarily speech articulation impairments. In addition, phonological processing measures were found to be good predictors of reading achievement. Results are discussed in terms of their implications for the early identification of developmental dyslexia. PMID- 24233764 TI - The orthographic code: Developmental trends in reading-disabled and normally achieving children. AB - An auditory rhyme detection task was employed to examine orthographic code development in 27 reading-disabled (RD) and 27 normally-achieving (NA) children ranging in age from 7-0 to 11-5. The amount of orthographic facilitation (that is, the reduction in response latencies for orthographically similar as opposed to orthographically dissimilar rhyme pairs) was recorded for each subject. Results indicated that RD children exhibit significantly less facilitation overall than NA children and that RD children do not demonstrate comparable orthographic facilitation effects to NA children until they are about two years older than their NA peers. It is concluded that children with a reading disability have a lessened ability to access automatically and make available stored lexical information relating to orthography. PMID- 24233765 TI - Phonological awareness training and remediation of analytic decoding deficits in a group of severe dyslexics. AB - The goal of the present study was to evaluate the effectiveness of the Auditory Discrimination in Depth Program (ADD) in remediating the analytic decoding deficits of a group of severe dyslexics. A group of ten severely dyslexic students ranging in age from 93 to 154 months were treated in a clinic setting for 38 to 124 hours (average of 65 hours). Pre- and post-treatment testing was done with the Woodcock Reading Mastery Test and the Lindamood Auditory Conceptualization to assess changes in phonological awareness and analytic decoding skills. Results revealed statistically significant gains in phonological awareness and analytic decoding skills. PMID- 24233766 TI - Early syntactic development of dyslexic children. AB - The syntactic development of preschoolers who later became disabled readers was compared to that of children who were similar to the dyslexics in sex, socioeconomic status, and IQ, but who became normal readers. Expressive and receptive syntactic abilities were examined longitudinally from age 30 to 60 months. The dyslexic group was poorer than the control group on all measures until the age of five, at which time both groups exhibited similar syntactic proficiency. The etiological relation of language development to reading disabilities is discussed. PMID- 24233767 TI - Linguistic profiles of dyslexic and good readers. AB - Linguistic profiles of 60 boys with average intelligence were examined at kindergarten, grade 2, and grade 4. The subjects were 7 dyslexic, 7 mildly dyslexic, 30 average, and 16 good readers, defined in terms of the discrepancy between standardized reading and intelligence scores. Across the three ages, reader groups did not differ in language comprehension, but did differ in confrontation and rapid automatized naming (RAN), three syntactic measures, and verbal memory. Group strengths and weaknesses were, with few exceptions apparent in kindergarten and maintained throughout. The kindergarten tasks which most effectively predicted reading group membership at grade 4 were giving letter sounds, and rapid naming; these predicted 4th grade reading group at close to 100 percent accuracy. The study, together with a further comparison of average and high IQ good readers, provides an interesting contrast between the role of RAN and Confrontation naming in reading. PMID- 24233769 TI - Foreword. PMID- 24233768 TI - Gestalt imagery: A critical factor in language comprehension. AB - Gestalt imagery-the ability to create imaged wholes-is a critical factor in oral and written language comprehension. Despite good decoding, good vocabulary, and adequate background experiences, many individuals experience weak gestalt imagery, thus processing "parts" rather than "wholes," from verbal stimuli, spoken or written. This contributes to a Language Comprehension Disorder that may be accompanied by a commonality of symptoms: weak reading comprehension, weak oral language comprehension, weak oral language expression, weak written language expression, difficulty following directions, and a weak sense of humor. Sequential stimulation using an inquiry technique develops gestalt imagery and results in significant improvement in reading comprehension. PMID- 24233770 TI - Brief review: Adoption of electronic medical records to enhance acute pain management. AB - PURPOSE: The purpose of this paper is to examine physician barriers to adopting electronic medical records (EMRs) as well as anesthesiologists' experiences with the EMRs used by the acute pain management service at two tertiary care centres in Canada. SOURCE: We first review the recent literature to determine if physician barriers to adoption are changing given the exponential growth of information technology and the evolving healthcare environment. We next report on institutional experience from two academic health sciences centres regarding the challenges they encountered over the past ten years in developing and implementing an electronic medical record system for acute pain management. PRINCIPAL FINDINGS: The key identified barriers to adoption of EMRs are financial, technological, and time constraints. These barriers are identical to those reported in a systematic review performed prior to 2009 and remain significant factors challenging implementation. These challenges were encountered during our institution's process of adopting EMRs specific to acute pain management. In addition, our findings emphasize the importance of physician participation in the development and implementation stages of EMRs in order to incorporate their feedback and ensure the EMR system is in keeping with their workflow. CONCLUSIONS: Use of EMRs will inevitably become the standard of care; however, many barriers persist to impede their implementation and adoption. These challenges to implementation can be facilitated by a corporate strategy for change that acknowledges the barriers and provides the resources for implementation. Adoption will facilitate benefits in communication, patient management, research, and improved patient safety. PMID- 24233771 TI - Brief review: Neuraxial analgesia in refractory malignant pain. AB - PURPOSE: This narrative review aims to inform health care practitioners of the current literature surrounding the use of intrathecal (IT) and epidural analgesia in cancer patients with refractory pain at end of life. Topics discussed and reviewed include: patient selection, treatment planning, procedure, equipment, medications, complications, policies and procedures, as well as directions for future research. PRINCIPAL FINDINGS: Cancer pain is inadequately treated in an estimated 10% of patients with malignant pain despite the implementation of the World Health Organization three-step analgesic ladder. This has prompted some to advocate for the addition of a fourth step that would include neuraxial interventions. There is moderate evidence supporting the safety and efficacy of IT drug therapy in cancer patients with refractory pain. A detailed assessment and interdisciplinary team approach is necessary to develop and implement care plans for patients requiring neuraxial analgesia. Neuraxial analgesia can significantly improve pain and reduce side effects, but this must be balanced against the increased complexity of care and the risk of uncommon but serious complications. CONCLUSION: Neuraxial drug delivery gives clinicians more options to manage refractory pain at end of life and should be offered to patients with intractable cancer pain. Teams should be interprofessional with clear delineation of roles and responsibilities. They should discuss advanced discharge planning with the patient prior to implantation as well as provide on-call support. PMID- 24233772 TI - Effect of Lactobacillus acidophilus and Bifidobacterium bifidum supplementation to standard triple therapy on Helicobacter pylori eradication and dynamic changes in intestinal flora. AB - To investigate Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium bifidum (B. bifidum) supplementation to triple therapy for Helicobacter pylori (H. pylori) eradication and dynamic changes in intestinal flora in children with H. pylori infection. One hundred H. pylori-infected children were randomly assigned to two groups: treatment group (n = 43), standard triple anti-H. pylori therapy plus probiotics of L. acidophilus and B. bifidum for 2 weeks followed by taking probiotics for another 4 weeks; control group (n = 45), standard triple anti-H. pylori therapy for 6 weeks. After 6-week treatment, 13C-urease breath test was performed and side effects were monitored during the observation period. Quantitative PCR with 16S rRNA-gene-targeted species-specific primers was carried out for the analysis of human intestinal B. bifidum, L. acidophilus, and Escherichia coli (E. coli). As expected, treatment group could significantly enhance the H. pylori eradication rate (83.7 vs. 64.4 %, P < 0.05). B. bifidum, L. acidophilus, and E. coli showed no statistical difference before or after therapy in the treatment group. The number of B. bifidum and L. acidophilus was significantly decreased after 2-week treatment in the control group, but after 6 week treatment it significantly increased and nearly returned to the level before treatment. The number of E. coli increased significantly after 2-week treatment, while after 6-week treatment, it nearly decreased to the level before treatment. L. acidophilus and B. bifidum supplementation is effective for H. pylori eradication compared with triple therapy alone. PMID- 24233774 TI - The present state and future direction of integrated gene function analysis. AB - The determination of the function of the protein products of genes has been a major focus of molecular biology since the founding of the discipline. The development of knock-in, knock-down, and transgenic methodologies has greatly speeded laboratory discoveries, while the development of high-throughput measurement technologies for many molecular species has led to the emergence of computational methods capable of predicting functional relationships between genes. In the future, we should see the emergence of quantitative models based on integrated data and laboratory methods that elucidate context-specific functions and identify how gene function depends on changing partners and contexts. PMID- 24233773 TI - Cold, pH and salt tolerant Penicillium spp. inhabit the high altitude soils in Himalaya, India. AB - Twenty five fungal cultures (Penicillium spp.), isolated from soil samples from the high altitudes in the Indian Himalayan region, have been characterized following polyphasic approach. Colony morphology performed on five different media gave varying results; potato dextrose agar being the best for the vegetative growth and sporulation as well. Microscopic observations revealed 18 isolates to be biverticillate and 7 monoverticillate. Based on the phenotypic characters (colony morphology and microscopy), all the isolates were designated to the genus Penicillium. Exposure to low temperature resulted in enhanced sporulation in 23 isolates, while it ceased in case of two. The fungal isolates produced watery exudates in varying amount that in many cases increased at low temperature. All the isolates could grow between 4 and 37 degrees C, (optimum 24 degrees C), hence considered psychrotolerant. While all the isolates could tolerate pH from 2 to 14 (optimum 5-9), 7 isolates tolerated pH 1.5 as well. While all the fungal isolates tolerated salt concentration above 10 %; 10 isolates showed tolerance above 20 %. Based on ITS region (ITS1-5.8S-ITS2) analysis the fungal isolates belonged to 25 different species of Penicillium (showing similarity between 95 and 100 %). Characters like tolerance for low temperature, wide range of pH, and high salt concentration, and enhancement in sporulation and production of secondary metabolites such as watery exudates at low temperature can be attributed to the ecological resilience possessed by these fungi for survival under low temperature environment of mountain ecosystem. PMID- 24233775 TI - Performing integrative functional genomics analysis in GeneWeaver.org. AB - Functional genomics experiments and analyses give rise to large sets of results, each typically quantifying the relation of molecular entities including genes, gene products, polymorphisms, and other genomic features with biological characteristics or processes. There is tremendous utility and value in using these data in an integrative fashion to find convergent evidence for the role of genes in various processes, to identify functionally similar molecular entities, or to compare processes based on their genomic correlates. However, these gene centered data are often deposited in diverse and non-interoperable stores. Therefore, integration requires biologists to implement computational algorithms and harmonization of gene identifiers both within and across species. The GeneWeaver web-based software system brings together a large data archive from diverse functional genomics data with a suite of combinatorial tools in an interactive environment. Account management features allow data and results to be shared among user-defined groups. Users can retrieve curated gene set data, upload, store, and share their own experimental results and perform integrative analyses including novel algorithmic approaches for set-set integration of genes and functions. PMID- 24233776 TI - Functional annotation of differentially regulated gene set using WebGestalt: a gene set predictive of response to ipilimumab in tumor biopsies. AB - Most high-throughput methods which are used in molecular biology generate gene lists. Interpreting large gene lists can reveal mechanistic insights and generate useful testable hypotheses. The process can be cumbersome and challenging. Multiple commercial and open solution currently exist that can aid researchers in the functional annotation of gene lists. The process of gene set annotation includes dataset preparation, which is method specific, gene list annotation and analysis and interpretation of the significant associations that were found. In this chapter, we demonstrate how WebGestalt can be applied to gene lists generated from transcriptional profiling data. PMID- 24233777 TI - Integrative data-mining tools to link gene and function. AB - Information derived from genomic and post-genomic data can be efficiently used to link gene and function. Several web-based platforms have been developed to mine these types of data by integrating different tools. This method paper is designed to allow the user to navigate these platforms in order to make functional predictions. The main focus is on phylogenetic distribution and physical clustering tools, but other tools such as pathway reconstruction, gene fusions, and analysis of high-throughput experimental data are also surveyed. PMID- 24233778 TI - Detection of driver protein complexes in breast cancer metastasis by large-scale transcriptome-interactome integration. AB - With the development of high-throughput gene expression profiling technologies came the opportunity to define genomic signatures predicting clinical condition or cancer patient outcome. However, such signatures show dependency on training set, lack of generalization, and instability, partly due to microarray data topology. Additional issues for analyzing tumor gene expression are that subtle molecular perturbations in driver genes leading to cancer and metastasis (masked in typical differential expression analysis) may provoke expression changes of greater amplitude in downstream genes (easily detected). In this chapter, we are describing an interactome-based algorithm, Interactome-Transcriptome Integration (ITI) that is used to find a generalizable signature for prediction of breast cancer relapse by superimposition of a large-scale protein-protein interaction data (human interactome) over several gene expression datasets. ITI extracts regions in the interactome whose expression is discriminating for predicting relapse-free survival in cancer and allow detection of subnetworks that constitutes a generalizable and stable genomic signature. In this chapter, we describe the practical aspects of running the full ITI pipeline (subnetwork detection and classification) on six microarray datasets. PMID- 24233779 TI - Pattern identification in time-course gene expression data with the CoGAPS matrix factorization. AB - Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset. PMID- 24233780 TI - Statistical tools and R software for cancer driver probabilities. AB - This chapter provides a description and illustration of CancerMutationAnalysis and Cancer MutationMCMC, two open source R packages specifically designed for the analysis of somatic mutations in cancer genome studies, at both the gene and gene set levels. PMID- 24233781 TI - Predicting the functional consequences of somatic missense mutations found in tumors. AB - Cancer-specific High-throughput Annotation of Somatic Mutations (CHASM) is a computational method that uses supervised machine learning to prioritize somatic missense mutations detected in tumor sequencing studies. Missense mutations are a key mechanism by which important cellular behaviors, such as cell growth, proliferation, and survival, are disrupted in cancer. However, only a fraction of the missense mutations observed in tumor genomes are expected to be cancer causing. Distinguishing tumorigenic "driver" mutations from their neutral "passenger" counterparts is currently a pressing problem in cancer research.CHASM trains a Random Forest classifier on driver mutations from the COSMIC databases and uses background nucleotide substitution rates observed in tumor sequencing data to model tumor type-specific passenger mutations. Each missense mutation is represented by quantitative features that fall into five major categories: physiochemical properties of amino acid residues; scores derived from multiple sequence alignments of protein or DNA; region-based amino acid sequence composition; predicted properties of local protein structure; and annotations from the UniProt feature tables. Both a software package and a Web server implementation of CHASM are available to facilitate high-throughput prioritization of somatic missense mutations from large, multi-tumor exome sequencing studies. After ranking candidate driver mutations with CHASM, the vector of features describing each mutation can be used to suggest possible mechanism by which mutations alter protein activity in tumorigenesis. This chapter details the application of both implementations of CHASM to tumor sequencing data. PMID- 24233782 TI - Determining the effect of DNA methylation on gene expression in cancer cells. AB - DNA methylation, a DNA modification by adding methyl group to cytosine, has an important role in the regulation of gene expression. DNA methylation is known to be associated with gene transcription by interfering with DNA-binding proteins, such as transcription factors. DNA methylation is closely related to tumorigenesis, and the methylation state of some genes can be used as a biomarker for tumorigenesis. Aberrant DNA methylation of genomic regions, including CpG islands, CpG shores, and first exons, is related to the altered gene expression pattern characteristics of all human cancers. Subheading 1 surveys recent developments on DNA methylation and gene expressions in cancer. Then we provide analysis of DNA methylation and gene expression in 30 breast cancer cell lines representing different tumor phenotypes. This study conducted an integrated analysis to identify the relationship between DNA methylation in various genomic regions and expression levels of downstream genes, using MethylCapseq data (affinity purification followed by next-generation sequencing of eluted DNA) and Affymetrix gene expression microarray data. The goal of this study was to assess genome-wide methylation profiles associated with different molecular subtypes of human breast cancer (luminal, basal A, and basal B) and to comprehensively investigate the effect of DNA methylation on gene expression in breast cancer phenotypes. This showed that methylation of genomic regions near transcription start sites, CpG island, CpG shore, and first exon was strongly associated with gene repression, and the effects of the regions on gene expression patterns were different for different molecular subtypes of breast cancer. The results further indicated that aberrant methylation of specific genomic regions was significantly associated with different breast cancer subtypes. PMID- 24233783 TI - Reverse engineering transcriptional gene networks. AB - The aim of this chapter is a step-by-step guide on how to infer gene networks from gene expression profiles. The definition of a gene network is given in Subheading 1, where the different types of networks are discussed. The chapter then guides the readers through a data-gathering process in order to build a compendium of gene expression profiles from a public repository. Gene expression profiles are then discretized and a statistical relationship between genes, called mutual information (MI), is computed. Gene pairs with insignificant MI scores are then discarded by applying one of the described pruning steps. The retained relationships are then used to build up a Boolean adjacency matrix used as input for a clustering algorithm to divide the network into modules (or communities). The gene network can then be used as a hypothesis generator for discovering gene function and analyzing gene signatures. Some case studies are presented, and an online web-tool called Netview is described. PMID- 24233785 TI - A method for inducible gene over-expression and down-regulation in emerging model species using Pogostick. AB - Nontraditional model species need new tools for the functional testing of genes, both conserved and lineage-specific genes. These tools should enable the exploration of gene function, either via knock-downs of endogenous genes or via over-expression and ectopic expression of transgenes. We constructed a new vector called Pogostick that can be used to over-express or down-regulate genes in organisms amenable to germ-line transformation by the piggyBac transposable element. The vector currently uses the heat-shock promoter Hsp70 from Drosophila melanogaster to drive transgene expression and, as such, will have immediate applicability to organisms that can correctly interpret this promotor sequence. Here we introduce the main features of Pogostick and how candidate genes can be inserted into the vector for use in either over-expression or down-regulation experiments. In addition, we also test Pogostick in two insect species, D. melanogaster and the emerging model butterfly Bicyclus anynana. We over-express the fluorescent protein DsRed during the larval and pupal stages of D. melanogaster development, and down-regulate DsRed in a line constitutively expressing this gene in the eyes. We then test the over-expression of Ultrabithorax (Ubx) in B. anynana, and obtain sequences flanking the Pogostick genomic insertions. This new vector will allow emerging model species to enter the field of functional genetics with few hurdles. PMID- 24233784 TI - Integrating in silico resources to map a signaling network. AB - The abundance of publicly available life science databases offers a wealth of information that can support interpretation of experimentally derived data and greatly enhance hypothesis generation. Protein interaction and functional networks are not simply new renditions of existing data: they provide the opportunity to gain insights into the specific physical and functional role a protein plays as part of the biological system. In this chapter, we describe different in silico tools that can quickly and conveniently retrieve data from existing data repositories and we discuss how the available tools are best utilized for different purposes. While emphasizing protein-protein interaction databases (e.g., BioGrid and IntAct), we also introduce metasearch platforms such as STRING and GeneMANIA, pathway databases (e.g., BioCarta and Pathway Commons), text mining approaches (e.g., PubMed and Chilibot), and resources for drug protein interactions, genetic information for model organisms and gene expression information based on microarray data mining. Furthermore, we provide a simple step-by-step protocol for building customized protein-protein interaction networks in Cytoscape, a powerful network assembly and visualization program, integrating data retrieved from these various databases. As we illustrate, generation of composite interaction networks enables investigators to extract significantly more information about a given biological system than utilization of a single database or sole reliance on primary literature. PMID- 24233786 TI - Construction and application of site-specific artificial nucleases for targeted gene editing. AB - Artificial nucleases have developed into powerful tools for introducing precise genome modifications in a wide variety of species. In this chapter the authors provide detailed protocols for rapidly constructing zinc finger nucleases (ZFNs) and TALE nucleases (TALENs) and evaluating their activity for the targeted generation of InDels within the zebrafish genome. PMID- 24233787 TI - Selection of recombinant antibodies from antibody gene libraries. AB - Antibodies are indispensable detection reagents for research and diagnostics and represent the biggest class of biological therapeutics on the market. In vitro antibody selection systems offer many advantages over animal-based technologies because the whole selection process is independent of the in vivo immune response. In the last two decades antibody phage display has evolved to the most robust and widely used method and has already yielded thousands of antibodies. The selection of binders by phage display is also referred to as "panning" and based on the specific molecular interaction of antibody phage with an immobilized antigen thus allowing the enrichment and isolation of antigen-specific monoclonal binders from very large antibody gene libraries. Here, we give detailed protocols for the selection of recombinant antibody fragments from antibody gene libraries in microtiter plates. PMID- 24233788 TI - Construction of simple and efficient siRNA validation systems for screening and identification of effective RNAi-targeted sequences from mammalian genes. AB - RNA interference (RNAi) is an evolutionarily conserved mechanism of gene silencing induced by double-stranded RNAs (dsRNAs). Among the widely used dsRNAs, small interfering RNAs (siRNAs) and short hairpin RNAs have evolved as extremely powerful and the most popular gene silencing reagents. The key challenge to achieving efficient gene silencing especially for the purpose of therapeutics is mainly dependent on the effectiveness and specificity of the selected RNAi targeted sequences. Practically, only a small number of dsRNAs are capable of inducing highly effective and sequence-specific gene silencing via RNAi mechanism. In addition, the efficiency of gene silencing induced by dsRNAs can only be experimentally examined based on inhibition of the target gene expression. Therefore, it is essential to develop a fully robust and comparative validation system for measuring the efficacy of designed dsRNAs. In this chapter, we focus our discussion on a reliable and quantitative reporter-based siRNA validation system that has been previously established in our laboratory. The system consists of a short synthetic DNA fragment containing an RNAi-targeted sequence of interest and two expression vectors for targeting reporter and triggering siRNA expressions. The efficiency of siRNAs is determined by their abilities to inhibit expression of the targeting reporters with easily quantified readouts including enhanced green fluorescence protein and firefly luciferase. Since only a readily available short synthetic DNA fragment is needed for constructing this reliable and efficient reporter-based siRNA validation system, this system not only provides a powerful strategy for screening highly effective RNAi-targeted sequences from mammalian genes but also implicates the use of RNAi based dsRNA reagents for reverse functional genomics and molecular therapeutics. PMID- 24233789 TI - Rapid genetic modification of mouse embryonic stem cells by Inducible Cassette Exchange recombination. AB - Embryonic stem cell (ESC) differentiation is a useful means by which to produce large quantities of cells in vitro representing early stages of embryonic development. A conditional gene expression system allows interrogation of factors at specific time points in the differentiation of ES cells to defined cell types. We have developed a method for rapidly generating conditional inducible murine ES cells by targeting genes into an Inducible Cassette Exchange (ICE) locus. The ICE locus encodes a doxycycline-inducible floxed Cre, which replaces itself with an incoming floxed gene of interest. The derivative cell lines, selected in G418, thus bear doxycycline-inducible transgenes. We provide detailed methods for performing ICE recombination and generating derivative doxycycline-inducible cell lines. PMID- 24233790 TI - In ovo electroporation of miRNA-based-plasmids to investigate gene function in the developing neural tube. AB - When studying gene function in vivo during development, gene expression has to be controlled in a precise temporal and spatial manner. Technologies based on RNA interference (RNAi) are well suited for such studies, as they allow for the efficient silencing of a gene of interest. In contrast to challenging and laborious approaches in mammalian systems, the use of RNAi in combination with oviparous animal models allows temporal control of gene silencing in a fast and precise manner. We have developed approaches using RNAi in the chicken embryo to analyze gene function during neural tube development. Here we describe the construction of plasmids that direct the expression of one or two artificial microRNAs (miRNAs) to knock down expression of endogenous protein/s of interest upon electroporation into the spinal cord. The miRNA cassette is directly linked to a fluorescent protein reporter, for the direct visualization of transfected cells. The transcripts are under the control of different promoters/enhancers which drive expression in genetically defined cell subpopulations in the neural tube. Mixing multiple RNAi vectors allows combinatorial knockdowns of two or more genes in different cell types of the spinal cord, thus permitting the analysis of complex cellular and molecular interactions in a fast and precise manner. The technique that we describe can easily be applied to other cell types in the neural tube, or even adapted to other organisms in developmental studies. PMID- 24233791 TI - Proteomic strategies: SILAC and 2D-DIGE-powerful tool to investigate cellular alterations. AB - Endothelial cells are highly sensitive to high doses of ionizing radiation and the cellular response leads to acute damage of the endothelium. This chapter describes how to measure the effects of ionizing radiation on the proteome of endothelial cells, here showing analysis at 4 and 24 h after exposure. Two complementary proteomic strategies, namely "stable isotope labeling by amino acids in cell culture" (SILAC) and 2D-DIGE analysis are used. In the example given, the exposure triggers considerable alterations in the endothelial protein expression with deregulated proteins categorized into four key pathways: (1) glycolysis/gluconeogenesis, (2) oxidative phosphorylation, (3) Rho-mediated cell motility, and (4) non-homologous end joining (NHEJ). After exposure to high-dose radiation, an immediate down-regulation is seen in the Ku70/Ku80 heterodimer and proliferating cell nuclear antigen (PCNA) proteins belonging to the NHEJ DNA repair pathway. Later time points show significant decrease in the expression levels of proteins of the oxidative phosphorylation (OXPHOS) pathway along with a significant expression increase in the enzymes of the glycolytic pathway. The methods to reproduce our analysis are presented here. PMID- 24233793 TI - Editorial introduction. PMID- 24233792 TI - Conditional gene-trap mutagenesis in zebrafish. AB - Zebrafish has become a widely used model for analysis of gene function. Several methods have been used to create mutations in this organism and thousands of mutant lines are available. However, all the conventional zebrafish mutations affect the gene in all cells at all time, making it difficult to determine tissue specific functions. We have adopted a FlEx Trap approach to generate conditional mutations in zebrafish by gene-trap mutagenesis. Combined with appropriate Cre or Flp lines, the insertional mutants not only allow spatial- and temporal-specific gene inactivation but also permit spatial- and temporal-specific rescue of the disrupted gene. We provide experimental details on how to generate and use such mutations. PMID- 24233794 TI - Bearing bad news: Dealing with the mimics of denial. AB - Denial is a common label for certain reactions to bad news. However, true denial is rare, and most cases actually represent a variety of responses with very different causes and needs. Three of these, disbelief, deferral, and dismissal, are characterized according to origins and needs. Failure to differentiate between these seemingly similar behaviors can result in inappropriate counseling, and interfere with attempts to convey information and provide support during a time of crisis. PMID- 24233795 TI - Phenotypic and genotypic heterogeneity in gaucher disease: Implications for genetic counseling. AB - Genetic counseling for Gaucher disease is complicated by the vast degree of clinical heterogeneity encountered in the disorder. Recent advances in our understanding of the molecular genetics of Gaucher disease are particularly relevant to genetic counseling. Although the identification of mutations in the glucocerebrosidase gene has enabled genotypic screening of Gaucher patients, the ability to reliably predict patient outcome on the basis of DNA studies is often limited. An appreciation of both the spectrum of clinical manifestations in Gaucher patients and the limitations of the available genotypic information is necessary when counseling patients, families and at-risk individuals. PMID- 24233796 TI - Variation in content in prenatal genetic counseling interviews. AB - Thirty non-MD genetic counselors from five cities described their pre-test interview for a client of advanced maternal age, indicating the frequency they addressed each of 16 topics. Near-universal were family history taking, procedural descriptions and complication rates, and the client's fetal risk level for certain disorders. Less frequently included were description of sex chromosome abnormalities with variable expression, choices if an abnormality is found, and description of actual abortion procedures (fewer than one-third always included this). Counselors cited client discomfort in minimizing abortion-related discussions. Both training programs and genetic services might stress conveying the differences in maternal risk associated with trimester of abortion, a factor arguably relevant to a client's informed decision making. Also, given U.S. demographic changes, they should consider increased staff training in cross cultural counseling techniques. PMID- 24233797 TI - A Spanish-language prenatal family health evaluation questionnaire: Construction and pilot implementation. AB - The Family Planning Council of America has constructed and implemented a genetic history questionnaire, the Family Health Evaluation, to elicit risk factors, to increase clients' knowledge about reproductive choices, and to improve access to genetic services. The objective of the present study was to develop and implement a Spanish-language version of the Family Health Evaluation for data collection and risk assessment. The content of the Family Health Evaluation was modified to more clearly reflect the risks, exposures, and medical needs of an Hispanic, largely Mexican-American, population. In the present study, the questionnaire was administered to women presenting for prenatal care. The data collected in this pilot study indicate that the questionnaire is effective in identifying individuals and families who would benefit from receiving additional information about a medical condition in their families, from genetic counseling or from a referral for high-resolution ultrasound or other diagnostic procedures. PMID- 24233798 TI - Maternal anxiety. PMID- 24233799 TI - Paternity testing: Is it a genetic counseling issue? PMID- 24233800 TI - Sociocultural and ethical dilemmas of genetic counseling-A suggested working approach. PMID- 24233801 TI - Immobilization ofmyo-inositol-1-phosphate synthase containing active, self regenerating coenzyme (NAD(+)) on the same matrix. AB - myo-Inositol-1-phosphate synthase (EC 5.5.1.4) from rat testes, an NAD(+) containing enzyme, which convertsD-glucose 6-phosphate to 1L-myo-inositol 1 phosphate, could be immobilized together with its cofactor and bovine serum albumin by crosslinking with glutaraldehyde at pH 4.5. The enzyme bound to the gel showed a specific activity of 5.6% of that of the native enzyme, but the activity could be increased to 21% by pretreatment with urea. PMID- 24233802 TI - Entrapment of living microbial cells in covalent polymeric networks : II. A quantitative study on the kinetics of oxidative phenol degradation by entrappedCandida tropicalis cells. AB - The kinetics of oxidative phenol degradation with microbial cellsCandida tropicalis, immobilized in a polyacrylamide and polymethacrylamide matrix, were mathematically simulated assuming zero-order and Michaelis-Menten rate equations.For zero-order kinetics an expanded equation for catalytic effectiveness as a function of the Thiele modulus, Biot number, and partition coefficients was derived and compared with numerical solutions for Michaelis Menten kinetics. Errors with regard to the zero-order approximation become negligible ifc o/K M >2.Experimentally determined catalyst activities as a function of particle size and cell concentration were compared to calculated ones. Additional experiments to determine the diffusion and oxygen consumption ratios have been carried out in an effort to resolve the physical parameters to be used in the above mentioned calculations.Furthermore, experiments on cell growth during reincubation with nutrients and oxygen are reported; an increase in activity up to a factor of ten was observed. These experiments demonstrate that the microbial cells are entrapped in the polymer matrix in the living state. PMID- 24233803 TI - Solid lactoperoxidase in the iodination ofL-tyrosine and albumin. AB - Solid lactoperoxidase (LP-sorbent) was prepared from lactoperoxidase and a carrier copolymer of maleic anhydride and butanediol divinylether. The properties of LP-sorbent in the iodination of tyrosine and albumin were examined. For optimizing the pH of the iodination mixture, buffers in the pH range 4.5-8.0 were used. Albumin was iodinated using Na(125)I and tyrosine using KI. The effect of substrate concentration and the sequential addition of reagents was examined in the iodination of tyrosine. The optimum pH, for iodination of albumin was 6.5 and that, for the iodination, of tyrosine 6.0-6.5. The iodination reactions were effective over a broad pH range around 6.5 resulting in almost equal iodinations. The optimum concentrations expressed as mmol/L/MUmol lactoperoxidase/mg sorbent at pH 6.5 were: H2O2, 70;, KI, 64; and tyrosine, 128. The maximum catalytic activity of the LP-sorbent at pH 6.5 was 4.22 MUkat/mg LP-sorbent or 28.8 kat/mol(mol of L-3-ITyr/s/mol lactoperoxidase). After the primary reaction of the LP-sorbent with hydrogen peroxide, both the supernatant and the washed solid phase exhibited iodinative activity. The iodination of tyrosine by LP-sorbent was also found to be possible in water. PMID- 24233804 TI - EPR characterization of cellulose triacetate fibers used for enzyme immobilization. AB - EPR studies of a nitroxide spin label and of the nitroxide spin-labeled albumin entrapped in cellulose triacetate fibers were carried out.The EPR spectra have shown that within the fiber only two phases are present: a liquid one of medium viscosity trapped inside microcavities, and a polymeric one surrounding them.After entrapment, spin-labeled albumin is distributed mainly in the liquid phase, though a not negligible amount of it remains within the polymeric matrix.The EPR studies have shown that, after the standard procedure of drying, the albumin is almost completely precipitated, but about 85% of it returns to solution when the fiber is again placed in the solution.The behavior of the albumin dissolved inside the microcavities toward denaturating agents and pH change, and that of the free albumin in solution is similar; the minor differences noticed indicate a second-order interaction between the fiber and the protein. PMID- 24233805 TI - Energy-transducing membrane : II. Roles of liquid crystal in the photoresponse of a chlorophyll liquid crystal membrane. AB - The states of chlorophyll a (Chl a) incorporated in a liquid crystal membrane were investigated by spectrophotometry in the visible and IR regions.N-(p methoxybenzylidene)-p'-butylaniline (MBBA) was used as the liquid crystal. The Chl a-MBBA (1?3 in molar ratio) showed the dihydrate-Chl a aggregate peak at 743 nm under excess water conditions. IR spectroscopic evidence indicated that the Chl a-MBBA membrane was hydrated in the dihydrate stoichiometry [Chl a-3MBBA 2H2O], via the C-10 ester OC...H(H)O...Mg and the C-9 keto OC...H(H)O...Mg bondings. PMID- 24233806 TI - Influence of urea and organic solvents on the activity of immobilizedmyo-inositol 1-phosphate synthase containing active, self-regenerating coenzyme (NAD(+)) on the same matrix. AB - myo-Inositol-1-phosphate synthase (EC 5.5.1.4.) from rat testes, an NAD(+) containing enzyme that convertsD-glucose 6-phosphate to 1L-myo-inositol-1 phosphate was immobilized together with its cofactor and bovine serum albumin by crosslinking with glutaraldehyde at pH 4.5. The cofactor is reduced and reoxidized during the reaction cycle, thus forming a self-regenerating system with respect to the cofactor. The behavior of this immobilized enzyme/cofactor system in presence of organic solvents and urea and the activating effect of these compounds on the enzymatic activity were studied and discussed in the paper. PMID- 24233807 TI - Support-bound microbial cells. PMID- 24233808 TI - Autocatalytic sets and biological specificity. AB - A universal feature of the biochemistry of any living system is that all the molecules and catalysts that are required for reactions of the system can be built up from an available food source by repeated application of reactions from within that system. RAF (reflexively autocatalytic and food-generated) theory provides a formal way to study such processes. Beginning with Kauffman's notion of "collectively autocatalytic sets," this theory has been further developed over the last decade with the discovery of efficient algorithms and new mathematical analysis. In this paper, we study how the behaviour of a simple binary polymer model can be extended to models where the pattern of catalysis more precisely reflects the ligation and cleavage reactions involved. We find that certain properties of these models are similar to, and can be accurately predicted from, the simple binary polymer model; however, other properties lead to slightly different estimates. We also establish a number of new results concerning the structure of RAFs in these systems. PMID- 24233809 TI - Pathogenetic role of magnesium deficiency in ophthalmic diseases. AB - Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases. PMID- 24233810 TI - Implementation of high-resolution manometry in the clinical practice of speech language pathology. AB - Visual imaging modalities, videofluoroscopic swallow study (VFSS) and fiberoptic endoscopic evaluation of swallow, for assessment of oropharyngeal dysphagia have been part of the speech language pathologist's (SLPs) armamentarium for the diagnosis and treatment of dysphagia for decades. Recently, the addition of high resolution manometry (HRM) has enabled the SLP to evaluate pharyngeal pressures and upper esophageal sphincter relaxation. Taken together, the use of visual imaging modalities with HRM can improve interpretation of swallowing physiology and facilitate more effective treatment planning. The goal of this article is to describe a clinical paradigm using HRM as an adjunct to VFSS, by the SLP, in the assessment of complex dysphagia. Moreover, in three cases described, the value of manometric measurements in elucidating swallowing imaging studies and documenting physiologic change in response to treatment is highlighted. As technology in this area is evolving, so will the clinical use of HRM by the SLP. Limitations of current HRM systems and applications are discussed. PMID- 24233811 TI - How to analyze the anticoagulant and antithrombotic mechanisms of action in fucanome and galactanome? AB - Through the perspective of the current glycomics age, fucanomics and galactanomics denote the international projects concerned with the studies of the biomedically active marine sulfated fucose- or galactose-composed polysaccharides, named sulfated fucans (SFs), and sulfated galactans(SGs), respectively. SFs and SGs are isolated from algae or marine invertebrates. The range of therapeutic actions of SFs and SGs is impressively broad. When certain structural requirements are found, some SFs and SGs may exhibit beneficial properties in inflammation, nociception, hemostasis (coagulation and thrombosis), vascular biology (angiogenesis), oncology, oxidative-stress, and virus infections. Although many biomedical applications for SFs and SGs have been pointed out over the past two decades, only inflammation, hemostasis, cancer, and vascular biology have their mechanisms of action satisfactorily elucidated. In addition, advanced structure-function relationships have been achieved only for the anticoagulant and antithrombotic activities, in which glycans of well-defined structures have been assayed. Because of this, the activities of SFs and SGs in stopping the clot and thrombus formation represent the closest therapeutic areas of having these glycans truly explored for drug development. Here, through an analytical viewpoint, we present the common methods and protocols employed to achieve such advanced structure-function relationships of SFs and SGs in anticoagulation and antithrombosis. PMID- 24233812 TI - Comparison of Non-invasive and Invasive Arterial Blood Pressure Measurement for Assessment of Dynamic Cerebral Autoregulation. AB - BACKGROUND: There is a growing interest in measuring cerebral autoregulation in patients with acute brain injury. Non-invasive finger photo-plethysmography (Finapres) is the method of choice to relate arterial blood pressure to changes in cerebral blood flow. Among acutely ill patients, however, peripheral vasoconstriction often limits the use of Finapres requiring direct intravascular blood pressure measurement. We evaluated how these two different forms of blood pressure monitoring affect the parameters of dynamic cerebral autoregulation (DCA). METHODS: We performed 37 simultaneous recordings of BP and cerebral blood flow velocity in 15 patients with acute brain injury. DCA was estimated in the frequency domain using transfer function analysis to calculate phase shift, gain, and coherence. In addition the mean velocity index (Mx) was calculated for assessment of DCA in the time domain. RESULTS: The mean patient age was 58.1 +/- 15.9 years, 80 % (n = 12) were women. We found good inter-method agreement between Finapres and direct intravascular measurement using Bland-Altman and correlation analyses. Finapres gives higher values for the efficiency of dynamic CA compared with values derived from radial artery catheter, as indicated by biases in the phase (26.3 +/- 11.6 degrees vs. 21.7 +/- 10.5 degrees , p = 0.001) and Mx (0.571 +/- 0.137 vs. 0.649 +/- 0.128, p < 0.001). Gain in the low frequency range did not significantly differ between the two arterial blood pressure methods. The average coherence between CBFV and ABP was higher when BP was measured with arterial catheter for frequencies above 0.05 Hz (0.8 vs. 0.73, p < 0.001). CONCLUSION: Overall, both methods yield similar results and can be used for the assessment of DCA. However, there was a small but significant difference for both mean Mx and phase shift, which would need to be adjusted for during monitoring of patients when using both methods. When available, invasive arterial blood pressure monitoring may improve accuracy and thus should be the preferred method for DCA assessment in the ICU. PMID- 24233813 TI - Stroke, IL-1ra, IL1RN, infection and outcome. AB - BACKGROUND: Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome. METHODS: Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism. RESULTS: In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome. CONCLUSIONS: These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke. PMID- 24233814 TI - The collaborative autonomy model of medical decision-making. AB - While the bioethical principle of beneficence originated in antiquity, the ascension of autonomy, or "self-rule," has redefined the physician-patient relationship to the extent that autonomy often dominates medical decision-making. Philosophical and social movements, medical research atrocities, consumerism, and case law have all had their influence on this paradigm shift. Consequently, the contemporary physician encounters an uncertainty in medical practice on how to resolve conflicts that arise in the pursuit of valuing both autonomy and beneficence. This is especially true in the practice of neurologic critical care where physicians may be advising comfort care measures for neurologically devastated patients while surrogates request physiologically futile interventions. This conundrum has been an important subject of the bioethics and social science literature but often this discourse is not disseminated to the clinicians confronting these issues. The purpose of this essay is to present a history of the principles of autonomy and beneficence and then present a shared medical decision-making model, collaborative autonomy, to provide guidance to neurologic critical care providers in how to resolve such dilemmas. Clinical vignettes will help illustrate the model. PMID- 24233815 TI - The physiologic effects of indomethacin test on CPP and ICP in severe traumatic brain injury (sTBI). AB - BACKGROUND: Refractory intracranial hypertension (RICH) is associated with high mortality in severe traumatic brain injury (sTBI). Indomethacin (INDO) can decrease intracranial cerebral pressure (ICP) improving cerebral pressure perfusion (CPP). Our aim was to determine modifications in ICP and CPP following INDO in RICH secondary to sTBI. METHODS: INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by continuous 2-h infusion period (0.5 mg/kg/h). Clinical outcome was assessed at 30 days according to Glasgow Outcome Scale (GOS). Differences in ICP and CPP values were assessed using repeated-measures ANOVA. Receiver operating characteristic curve (AUC) was used for discrimination in predicting 30-day survival and good functional outcome (GOS 4 or 5). Analysis of INDO safety profile was also conducted. RESULTS: Thirty-two patients were included. Median GCS score was 6 (interquartile range: 4-7). The most frequent CT finding was the evacuated mass lesion (EML) according to Marshall classification (28.1 %). Mortality rate was 34.4 %. Within 15 min of INDO infusion, ICP decreased (Delta%: -54.6 %; P < 0.0001), CPP increased (Delta%: +44.0 %; P < 0.0001), and the remaining was stable during the entire infusion period. Patients with good outcome (n = 12) showed a greater increase of CPP during INDO test (P = 0.028). CPP response to INDO test discriminated moderately well surviving patients (AUC = 0.751; P = 0.0098) and those with good functional recovery (AUC = 0.763; P = 0.0035) from those who died and from those with worse functional outcome, respectively. No adverse events were observed. CONCLUSIONS: INDO appears effective in reducing ICP and improving CPP in RICH. INDO test could be a useful tool in identifying RICH patients with favorable outcome. Future studies are needed. PMID- 24233817 TI - Apnea testing for brain death in severe acute respiratory distress syndrome: a possible solution. AB - INTRODUCTION: A 42-year-old man with a subarachnoid hemorrhage complicated by anoxic brain injury, respiratory failure requiring mechanical ventilation, and severe acute respiratory distress syndrome (ARDS) presented a clinical conundrum for safe apnea testing in brain death determination due to profound hypoxemia. METHODS: Case report. RESULTS: During brain death examination, despite meeting criteria for severe ARDS, apnea testing was successfully completed with the use of a pretest recruitment maneuver and 20 cm H(2)O CPAP valve. CONCLUSION: A recruitment maneuver and CPAP valve may be used in severe ARDS for safe apnea testing in brain death determination. PMID- 24233816 TI - Identifying risk factors for central pontine and extrapontine myelinolysis after liver transplantation: a case-control study. AB - BACKGROUND: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome. METHODS: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4 %) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score. RESULTS: The 19 patients with CPEPM (7F, mean age 52.1 +/- 2 years) had a mean MELD score of 26 +/- 2.2. Before OLT, patients who develop CPEPM presented more frequently low (<130 mmol/l; p < 0.04) and very low (<125 mmol/l; p < 0.009) sodium than controls. In patients developing CPEPM, the number of platelet units and fresh frozen plasma transfused during surgery was higher (p = 0.05 and 0.047), hemorrhagic complications were more frequent after OLT (p = 0.049), and variations of sodium before and after OLT were higher (p = 0.023). The association of >2 of these conditions were strongly associated with CPEPM (p = 0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13 %, p < 0.0001). CONCLUSIONS: High MELD score patients undergoing OLT, receiving massive perfusions of Na-rich products, experiencing surgery-related hemorrhagic complication and important fluctuations of Na are at risk of developing CPEPM. Therefore careful monitoring of natremia in the perioperative period and use of water-free perfusion in case of massive blood-products transfusion are critical points of this patient management. PMID- 24233819 TI - Can social bees be influenced to choose a specific feeding station by adding the scent of the station to the hive air? AB - The behavioral response of honeybees (Apis mellifera L.) and bumblebees (Bombus terrestris L.) to the flower volatiles 2-ethyl-1-hexanol and myrcene isolated in situ from white clover (Trifolium repens L.) and oil seed rape (Brassica napus oleifera), respectively, were investigated on a rotating arena with 12 visually identical, but differently scented, feeding stations. When locating a feeding station, neutral in both shape and color, foragers used scent as orientation cue. Introduction of 2-ethyl-1-hexanol to the honeybee hives induced significantly more visits to sites containing this compound. In contrast, introduction of myrcene to the hives did not influence the foraging choices of honeybees significantly. No effect of hive scent composition on the choices made by bumblebees could be detected. "Experienced" bumble bees, i.e., bees with more than five visits to the feeding stations, tended to visit a particular position on the arena without discriminating between the two volatiles. In contrast, honeybees showed no positioning behavior on the arena, using primarily odoriferous stimuli. The observed influences of addition of scents to the hives are discussed in relation to the general knowledge on foraging behavior of social bees and the emission of volatiles from leaves and flowers. PMID- 24233820 TI - Antennal perception of oilseed rape,Brassica napus (Brassicaceae), volatiles by the cabbage seed weevilCeutorhynchus assimilis (Coleoptera, Curculionidae). AB - The response of theCeutorhynchus assimilis antenna to volatiles in air entrainment-derived extracts of oilseed rape,Brassica napus, was studied using coupled gas chromatography (GC)-electroantennography (EAG) and coupled GC-single cell recording (SCR). By means of these techniques and coupled gas chromatography mass spectrometry (GC-MS), 25 active compounds were identified, including isoprenoids and compounds derived from fatty acids and amino acids. Some of the latter, the isothiocyanates and goitrin, and probably indole and benzyl cyanide, are catabolites of glucosinolates. The electrophysiological activity of the identified compounds was confirmed by EAG using a physiologically discriminating dose, and by SCR studies. The importance of the combined use of the EAG and SCR techniques was demonstrated, since specific olfactory cells were located for five compounds that did not elicit significant EAG responses. The majority of the olfactory cells from which single cell recordings were obtained showed very high specificity, and in numerous recordings there were consistent pairings of specific cell types. PMID- 24233821 TI - Isolation, purification, and characterization of newDaphnia-toxic compound from axenicMicrocystis flos-aquae strain PCC7806. AB - A new compound, that is toxic toDaphnia, called theDaphnia-toxic compound (DTC), was isolated and purified from water extracts ofMicrocystis PCC7806. An establishedDaphnia-bioassay was used as a detection system for the DTC in purified fractions. Temperature and pH stability were used to separate DTC from unstable compounds by changing the pH while the temperature was kept at 90 degrees C. This was followed by ultracentrifugation at 100.000g. A molecular cutoff filtration technique was used to separate compounds with a molecular weight >100,000 Da and to reduce the volume of the fraction that was >500 Da. Evaporation in a vacuum led to a fraction that had a suitable volume for further characterization procedures. DTC was resistant to degradation by two bacteria that were isolated from a laboratory culture. DTC was not inactivated by incubation with protease K or pronase E. A strong anion-exchange resin at the stationary phase of the FPLC equipment was used to purify and concentrate the DTC. The molecular weight determined by gel filtration was between 1.0 and 3.1 kDa. A UV spectrum from this purified fraction exhibited absorption maxima at 220, 260, and 360 nm. The ecological and analytical relevance of the DTC is compared with microcystins. PMID- 24233818 TI - Differential disruption of blood-brain barrier in severe traumatic brain injury. AB - BACKGROUND: Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood-brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)-plasma albumin quotient of >=0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI. METHODS: We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein. RESULTS: Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF-plasma albumin quotient of >=0.007. There were strong positive correlations seen among CSF-plasma albumin quotient and CSF-plasma immunoglobulin-G quotient and CSF-plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption. CONCLUSIONS: In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF-plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF-plasma albumin quotient for evaluating BBB dysfunction. PMID- 24233822 TI - Quadrupole storage mass spectrometry of mono- and dimethylalkanes. AB - Monomethyl and dimethylalkanes with one, two, three, four, five, and seven methylene groups separating the methyl branches were synthesized and analyzed by magnetic sector and quadrupole storage (ion trap) mass spectrometry. The spectra produced by the magnetic sector instrument were in good agreement with previously reported data, whereas the ion trap spectrometer produced ions resulting from cleavages adjacent to the branching points, markedly different than those from the magnetic sector instrument. Fragmentation patterns show that the ion trap mass spectrometer can be used to characterize branched alkanes in nanogram and subnanogram quantities. PMID- 24233823 TI - Host-specific recognition kairomone for the parasitoidMicroplitis croceipes (Cresson). AB - A water-extractable host recognition kairomone in frass of corn earworm,Helicoverpa zea Boddie (Lepidoptera: Noctuidae), host larvae stimulates antennation by females of the parasitoidMicroplitis croceipes Cresson (Braconidae: Hymenoptera). In addition, when the wasps contact water extracts of host frass they will subsequently fly in a flight tunnel to odor associated with the extract. Contact with water extracts of cowpea leaves or with water extracts of frass from larvae of nonhost beet armyworm, fall armyworm, or cabbage looper that were fed cowpea leaves does not stimulate antennation, nor do wasps fly to associated odors after contact with these substances. However, contact with the water extract of host frass in association with hexane extract of cowpea-fed nonhost frass will induce the wasps to subsequently fly to the hexane extract of the nonhost frass when it is used as an odor source in a flight tunnel. Thus the host-specific kairomone by whichM. croceipes recognizes the frass of its host is extractable with water. This substance plays a crucial role in the foraging behavior of this parasitoid by allowing it to recognize host frass and to learn to search for odors originating from plants on which the host is feeding. PMID- 24233824 TI - Chemical analysis of sternal gland secretion of paper waspPolistes dominulus (Christ) and its social parasitePolistes sulcifer (Zimmermann) (Hymenoptera: Vespidae). AB - The secretion of the tegumental glands of the fifth and sixth gastral sternites ofP. dominulus and of its social parasiteP. sulcifer was analyzed by gas chromatography-mass spectrometry. Seven long-chain carboxylic acids have been identified: hexadecanoic, octadecadienoic and octadecenoic acids are the major components of the gland secretion ofP. dominulus and octadecenoic acid the main compounds ofP. sulcifer sternal gland secretion. The same carboxylic acids have been found on the nest pedicel. PMID- 24233825 TI - Allocation of pederin during lifetime ofPaederus rove beetles (Coleoptera: Staphylinidae): Evidence for polymorphism of hemolymph toxin. AB - Pederin, a hemolymph toxin found in the rove beetle genusPaederus, is quantified in individual specimens ofP. fuscipes andP. riparius. Whereas males always contain only small quantities of the toxin (0.1-1.5 ug), females are not so restricted (0.2-20.5 ug) and in most cases possess roughly 10-fold that in males. There are, however, females containing as little pederin as the males, and so two clearly separate groups of females can be discerned. These two groups hint at two types of females defined by the eggs they lay. About 85% of the females, i.e., those containing much of the substance, transfer pederin into every egg and thus are denoted (+)-females. The remaining 15%, the (-)-females, contain at best small amounts of the toxin, which is transferred in minute quantities into the first eggs while the subsequent ones lack pederin. With respect to the pederin content of their eggs, there is no overlap between these two types of females. If fed with pederin, (-)-females can transfer it into the eggs like (+)-females. After hatching the larvae store pederin when present. Larvae are not able to biosynthesize the toxin on their own, but storage of that received in the egg is very efficient, and the difference between larvae with and without pederin is preserved until imaginal eclosion. In (+)-females, pederin increases, probably reflecting a biosynthetic capacity, but in males and presumptive (-)-females the amount of pederin never exceeds the quantity transferred by parental (+)-females. Consequently, males and (-)-females probably are unable to biosynthesize pederin. This polymorphism of females may have a genetic basis. Individuals of all stages nevertheless sequester pederin if it is supplied with the diet. PMID- 24233826 TI - Structure-activity relationships of cyclopentane analogs of jasmonic acid for induced responses of canola seedlings,Brassica napus L. AB - Jasmonic acid (JA) has potent activity in enhancing cotyledon toughness and stimulating the biosynthesis of 3-indolymethyl glucosinolate in seedlings of canola,Brassica napus L. Structure-activity relationships among cyclopentane analogs of JA revealed that maximum activity in both systems was achieved when an acetyl side chain (or a methylated acetyl side chain) occurred at the C-1 ring position, ann-pentenyl side chain at the C-2 ring position, and a keto group at the C-3 ring position. Although coronatine and coronafacic acid both possess a cyclopentane ring with a keto group at the C-3 position, only coronatine was active inB. napus seedlings. Coronatine, a chlorosis-inducing toxin essential to the infectivity of pathovars ofPseudomonas syringae, acted as a complete molecular mimic of JA and had the same stimulatory effect on specific indole glucosinolates inBrassica species, thereby casting doubt on the hypothesis that indole glucosinolates serve in bacterial pathogen defense. Similarities and differences for structural requirements for activity among several diverse physiological systems affected by jasmonates likely reflect species-, tissue-, and developmental-specific differences. PMID- 24233827 TI - Neutral compounds from male castoreum of North American beaver,Castor canadensis. AB - North American beavers (Castor canadensis) mark their territories with castoreum, the strong-smelling paste in their castor sacs. In their own territories, beavers respond with scent marking to experimental scent marks that consist of strange castoreum (or selected components). In part, the unique odor of castoreum is due to large amounts of phenolic compounds and neutral compounds. Purified neutral compounds were analyzed by GC. GC-MS, and NMR; identities of the neutral compounds were confirmed by comparing the properties of authentic compounds with those of the isolated compounds. We identified 13 neutral compounds that had not been reported before for castoreum. Most of these are oxygen-containing monoterpenes. Of the nine neutral compounds reported by Lederer (1949), only three are confirmed in our analysis; the other six neutral compounds are either absent or are not volatile enough to be detected by our methods. Eight compounds 6-methyl-l-heptanol, 4,6-dimethyl-l-heptanol, isopinocamphone, pinocamphone, two linalool oxides, and their acetates-were synthesized for structure identification and bioassays. PMID- 24233828 TI - Aggregation pheromone ofCarpophilus dimidiatus (F.) (Coleoptera: Nitidulidae) and responses toCarpophilus pheromones in South Carolina. AB - The major component of the male-produced aggregation pheromone ofCarpophilus dimidiatus (F.) is (3E, 5E, 7E, 9E)-6,8-diethyl-4-methyl-3,5,7,9-dodecatetraene. It attracts beetles of both sexes in the field and is synergized by odors from fermenting bread dough; mean trap catches for the tetraene alone, tetraene plus dough, dough alone, and control were 24.5, 48.3, 0.02, and 0.00, respectively. In the laboratory, individual males produced 0.58 ug+/-0.35 ug (SD) of the tetraene per day, but males in groups of 10-50 produced <2% as much per beetle. A second male-specific compound, (3E, 5E, 7E, 9E)-5,7-diethyl-9-methyl-3,5,7,9 tridecatetraene, was also identified fromC. dimidiatus and is about 5% as abundant as the major pheromone component.Carpophilus flight activity was monitored for one year in South Carolina corn fields with the pheromones forC. dimidiatus, C. freemani Dobson,C. mutilatus Erichson,C. hemipterus (L.),C. lugubris Murray, andC. obsoletus Erichson, all in combination with bread dough. The first four of these species accounted for 18, 70, 5.7, and 0.03%, respectively, of the totalCarpophilus trapped, but noC. lugubris orC. obsoletus were captured. Captures ofC. freemani were as high as 11,400/trap/week. Species specificity for the first four pheromones was high, except that a synthetic impurity in theC. dimidiatus pheromone was somewhat attractive toC. freemani andC. mutilatus. Three other species captured.C. antiques Melsheimer,C. marginellus Motschulsky, andC. humeralis (F.), accounted for 0.005, 5.0, and 1.3% of the total catch, respectively.C. antiquus was attracted primarily to the pheromone ofC. dimidiatus, butC. marginellus andC. humeralis responded to most of the test pheromones. There were two major periods ofCarpophilus flight activity: February through June and September through November. PMID- 24233829 TI - Phloem transport of antirrhinoside, an iridoid glycoside, inAsarina scandens (Scrophulariaceae). AB - Iridoid glycosides, terpene-derived compounds found in many plant families, protect the plant against generalist and nonadapted specialist insect herbivores, fungi, and bacteria. Antirrhinoside, a common iridoid glycoside in the tribe Antirrhineae (Scrophulariaceae), was rapidly labeled when mature leaves ofAsarina scandens were exposed to(14)CO2. Antirrhinoside was translocated in the phloem along with sucrose. Radiolabeled antirrhinoside appeared in the petiole of the labeled leaf within 20 min of the beginning of the labeling period. Antirrhinoside was also found in phloem sap obtained by the EDTA method. PMID- 24233830 TI - Role of volatile inforchemicals emitted by feces of larvae in host-searching behavior of parasitoidCotesia rubecula (Hymenoptera: Braconidae): A behavioral and chemical study. AB - The role of volatile infochemicals emitted by feces of larvae in the host searching behavior of the parasitoidCotesia rubecula was evaluated during single- and dual-choice tests inside a wind tunnel. The following treatments were tested: feces produced by second and fourth instars ofPieris rapae (preferred host), second instars ofP. brassicae (inferior host), second instars ofP. napi (nonhost), and wet feces of second instars ofP. rapae. During a single-choice situation females ofC. rubecula oriented to all types of feces tested. When a preference was to be made,C. rubecula preferred feces of second instars ofP. rapae over that of fourth, feces ofP. rapae over that ofP. brassicae, feces ofP. napi over that ofP. brassicae, and wet over normal host feces. No preference was exhibited between feces of second instars ofP. napi and that of second instars ofP. rapae. The relative importance of infochemicals from host feces versus plant damage caused by host larvae to the searching behavior ofC. rubecula was also evaluated. Plant damage was more important to the searching females than host feces when feces were present in specific concentrations in relation to damage. The volatiles released by normal and wet feces of second instars ofP. rapae, wet feces of fourth instars ofP. rapae, and normal and wet feces ofP. brassicae were collected and identified. Overall, 85 chemical compounds were recorded belonging to the following chemical groups: alcohols, ketones, aldehydes, esters, isothiocyanates, sulfides, nitriles, furanoids, terpenoids and pyridines. The blend of chemicals emitted by feces of different instars ofP. rapae and different species ofPieris exhibited an instar and species specificity in both quantity and quality. Wetting of normal feces increased the amount of volatile chemicals released, and it was also responsible for the appearance of new compounds. The role of feces of larvae in the host-seeking behavior ofC. rubecula is discussed. PMID- 24233831 TI - Identification of sex attractant pheromone components of the tussock moth,Euproctis taiwana (Shiraki) (Lepidoptera: Lymantriidae). AB - Two compounds were isolated and identified from abdominal tips of the female tussock moth,Euproctis taiwana (Shiraki), by a combination of gas chromatography electroantennographic detection, coupled gas chromatography-mass spectrometric analysis, microreaction, and synthesis. These compounds were (Z)-16-methyl-9 heptadecenyl isobutyrate (74.8%) and 16-methylheptadecyl isobutyrate (25.2%). Their total amount was determined to be ca. 29.8 ng/female. Field bioassays showed that (Z)-16-methyl-9-heptadecenyl isobutyrate is a sex attractant for the male moths. These chemical compounds had not previously been found as the sex pheromone components in the genusEuproctis. PMID- 24233832 TI - Electroantennographic and coupled gas chromatographic-electroantennographic responses of the mediterranean fruit fly,Ceratitis capitata, to male-produced volatiles and mango odor. AB - We have identified five compounds from the headspace of calling male Mediterranean fruit flies (medfly),Ceratitis capitata (Wiedemann), and three compounds from the headspace of ripe mango (Mangifera indica L). using coupled gas chromatographic-electroantennographic (GC-EAG) recordings, coupled gas chromatographic-mass spectrometric (GC-MS) analysis, and electroantennographic (EAG) assays of standards. The male-produced volatiles eliciting responses from female antennae were ethyl-(E)-3-octenoate, geranyl acetate, (E,E)-alpha farnesene, linalool, and indole. An EAG dose-response test of linalool enantiomers and indole with female medfly antennae showed relatively strong EAG activities, but no significant difference between (R)-(-)-linalool and (S)-(+) linalool. The three mango volatiles were identified as (1S)-(-)-beta-pinene, ethyl octanoate, andbeta-caryophyllene. In addition, a strong antennal response was recorded from a contaminant,alpha-copaene, present in a commercial sample ofbeta-caryophyllene. The EAG response amplitudes from both male and female antennae to the above three mango volatiles were significantly greater than to a hexanol control. For both male and female medfly antennae, the greatest EAG responses were elicited bybeta-caryophyllene followed by ethyl octanoate. The mean EAG responses of female antennae tobeta-caryophyllene and (1S)-(-)-beta pinene were significantly greater than those of male antennae. PMID- 24233833 TI - Roles of cuticular hydrocarbons in intra-and interspecific recognition behavior of two rhinotermitidae species. AB - Soldiers of two termite species.Reticulitermes speratus andCoptotermes formosanus, showed aggressive behavior toward workers of other species. Soldiers always exhibited aggressive behavior to a conspecific worker treated with heterospecific cuticular hydrocarbons. A bioassay using live workers to test contact chemical cues was developed. PMID- 24233834 TI - Evaluation of organic infusions and synthetic compounds mediating oviposition inAedes albopictus andAedes aegypti (Diptera: Culicidae). AB - Oviposition responses of gravidAedes albopictus andAe. aegypti were evaluated to natural organic infusions (hay infusion, larval rearing water, and field collected larval water) as well as compounds isolated from hay infusion (3 methylindole, 4-methylphenol, 4-ethylphenol, indole, and phenol) known to elicit oviposition inCulex mosquitoes. In laboratory bioassays, significant oviposition responses were obtained fromAe. albopictus, but not fromAe. aegypti, to dilutions of hay infusion and field water. Oviposition responses of both species were moderate to the synthetic compounds tested in the laboratory (0.01-100 ug/liter). Only 3-methylindole (0.1 ug/liter) and 4-ethylphenol (1.0 ug/liter) elicited significantly more oviposition byAe. albopictus than did well water. Of the synthetic compounds tested withAe. aegypti, only phenol (1.0 ug/liter) and 4 ethylphenol (0.1 ug/liter) elicited significantly more oviposition than did well water. Significant repellency or oviposition deterrence for both species occurred in response to at least one high concentration of most of the compounds tested. In field cage evaluations, oviposition responses byAe. albopictus were strongest to larval water and field water, moderate to hay infusion and 3-methylindole (100 ug/liter), and low to well water. A mixture of five synthetic compounds mimicking hay infusion was no more effective than 3-methylindole alone. ForAe. aegypti, oviposition responses were greatest to larval water and least to 3-methylindole. In an olfactometer, gravid females of both species oriented more to field water than to well water and onlyAe. albopictus oriented more to larval water or hay infusion than well water. In general, gravidAe. albopictus responded more strongly to oviposition stimuli than didAe. aegypti. PMID- 24233835 TI - Attractants fromStaphylococcus aureus cultures for Mexican fruit fly,Anastrepha ludens. AB - Volatile chemicals from tryptic soy broth cultures ofStaphylococcus aureus that attract sugar-fed, protein-hungry adult Mexican fruit flies were identified. Chemicals identified from the headspace above the filtrate of the bacterial cultures were ammonia, trimethylamine, isoamylamine, 2-methylbutylamine, 2,5 dimethylpyrazine, and acetic acid. Each chemical attracted flies. A mixture of the chemicals in the same concentrations as were found in the bacterial filtrate was 89% as effective in attracting flies as the bacterial filtrate in laboratory bioassays. Additional chemicals were identified from various concentrated or pH altered preparations made from the filtrate. Many of these chemicals also attracted flies. One of these chemicals, dimethylamine, was the most effective chemical identified. The use of solid-phase microextraction for volatile collection and of thick-film (5-um) capillary GC columns was essential to the success of this work. PMID- 24233836 TI - Synergism of an insect sex pheromone specialist neuron: Implications for component identification and receptor interactions. AB - Extracellular recordings show that the response to the sex pheromone component, (Z)-7-dodecenyl acetate (Z7-12:Ac) by the HS(a) antennal olfactory specialist neuron of the cabbage looper,Trichoplusia ni (Hubner), is synergized by two synthetic sex pheromone analogs and two components of the female sex pheromone. Complementary behavioral measures of upwind flight and copulatory responses to mixtures ofZ7-12:Ac with the analogs and sex pheromone components in a wind tunnel produced behavioral evidence consistent with the neuron's electrophysiological responses. The phenomenon of receptor neuron synergism impacts several areas and provides a note of caution for common practices of identifying secondary sex pheromone components only from field traps and/or wind tunnel tests. PMID- 24233837 TI - The author M.B. Dicklor should be added to author names and the following change made in the text. PMID- 24233838 TI - SOX2 regulates apoptosis through MAP4K4-survivin signaling pathway in human lung cancer cells. AB - Previous studies have implicated cancer stem cells in tumor recurrence and revealed that the stem cell gene SOX2 plays an important role in the tumor cell resistance to apoptosis. Nonetheless, the mechanism by which SOX2 regulates apoptosis signals remained undefined. Here, we demonstrated the surprising finding that silencing of the SOX2 gene effectively induces apoptosis via the activation of death receptor and mitochondrial signaling pathways in human non small cell lung cancer cells. Unexpectedly, reverse transcription-PCR analysis suggested that downregulation of SOX2 leads to activation of MAP4K4, previously implicated in cell survival. Evaluation of the apoptotic pathways revealed an increased expression of key inducers of apoptosis, including tumor necrosis factor-alpha and p53, with concurrent attenuation of Survivin. Although p53 appeared dispensable for this pathway, the loss of Survivin in SOX2-deficient cells appeared critical for the observed MAP4K4 induced cell death. Rescue experiments revealed that SOX2-silencing-mediated killing was blocked by ectopic expression of Survivin, or by reduction of MAP4K4 expression. Clinically, expressions of Survivin and SOX2 were highly correlated with each other. The results reveal a key target of SOX2 expression and highlight the unexpected context-dependent role for MAP4K4, a pluripotent activator of several mitogen activated protein kinase pathways, in regulating tumor cell survival. PMID- 24233839 TI - Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identifying activated RTKs in HCC is critical for developing new molecularly targeted therapies. Using a phospho-RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. The knockdown of Axl by RNA interference significantly reduced cell migration and invasion in the HCC cell lines HA22T and Mahlavu. Stimulation of HCC cell lines by Axl ligand growth arrest-specific 6 (Gas6) enhanced cell migration and invasion. The Gas6/Axl pathway enhanced the expression of the epithelial-mesenchymal transition-inducing transcription factor Slug, which is essential for the invasion-promoting activity of Axl. Treating HCC cells with the Axl inhibitor bosutinib suppressed Slug expression and decreased the invasiveness of HCC cell lines. These findings indicate that Gas6/Axl regulates tumor invasion through the transcriptional activation of Slug. PMID- 24233840 TI - Materialism and Life Satisfaction: The Role of Religion. AB - This study examines the role of religion and religiosity in the relationship between materialism and life satisfaction. The findings suggests that religion may be a key factor in understanding differences in findings of previous studies regarding the inverse relationship found in the vast majority of previous studies. Based on a large-scale study in Malaysia-a country comprised of several religious subcultures (mainly Muslims, Buddhists, and Hindus), the findings suggest that the influence of religiosity on materialism and life satisfaction is stronger among Malays than among Chinese and Indians, and life satisfaction partially mediates the relationship between religiosity and materialism. The paper discusses implications for theory development and further research. PMID- 24233843 TI - The factorial structure of pathological gambling. AB - Pathological gambling has been characterised by DSM-III-R and DSM-IV as a disorder of impulse control with a proportion of gamblers identified as meeting criteria for a co-morbid diagnosis of Antisocial Personality Disorder. To date, empirical evidence in support of the notion that pathological gamblers as a group manifest elevated traits of impulsivity remains equivocal. Principal components analysis was used to investigate relationships between the constructs of impulsivity, psychopathy, DSM-III-R criteria for Antisocial Personality Disorder, psychological distress, criminal offending behavior and a range of other common psychological measures employed with pathological gamblers. The sample comprised 115 pathological gamblers, 80 consecutive gamblers seeking treatment from a general hospital psychiatric inpatient behavior therapy unit, and 35 volunteer Gamblers Anonymous attenders. Four primary factors were determined: psychological distress, sensation seeking, crime and liveliness, and impulsive-antisocial. Results suggest that pathological gambling consists of a number of discrete and reproducible factorial structures. The impulsive antisocial factor was found to be associated with gambling behavior and indices of poor psychosocial functioning. PMID- 24233842 TI - Progranulin, a major secreted protein of mouse adipose-derived stem cells, inhibits light-induced retinal degeneration. AB - Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina. PMID- 24233844 TI - Clinical obstacles in administrating the South Oaks Gambling Screen in a methadone and alcohol clinic. AB - The South Oaks Gambling Screen (SOGS) was administered to veterans in both an outpatient methadone and problem drinking clinic. The instrument was given to 93 veterans who represented the poor and homeless. It was anticipated that the SOGS would provide important diagnostic information to the clinicians counseling the substance abusing population since many compulsive gamblers have a history of substance abuse. A number of clinical obstacles were encountered in administrating the SOGS in this environment. Both Client and staff noncompliance during the screening were major concerns in this respect. The clinical obstacles encountered in this study were examined and suggestions to prevent these problems are discussed. PMID- 24233845 TI - Pathological gambling and criminal culpability: An analysis of forensic evaluations presented to German penal courts. AB - In Germany penal courts and expert witnesses are being confronted with an increasing number of offenders claiming that their criminal behavior had been caused by an irresistible urge to gamble. In 48 of 56 evaluated cases the defendants were diagnosed as pathological gamblers. However, diminished culpability (S 21 German Criminal Code) was granted in only 32 cases. In these cases the illegal activity to get money could be classified as primarily gambling related. PMID- 24233846 TI - A developmental perspective of gambling behavior in children and adolescents. AB - Although it has been determined that gambling is a popular activity amongst the young, there seems to be a lack of studies examining developmental differences in children's gambling behavior. This study examines developmental differences in children's blackjack gambling behavior. One hundred and four students (51 males; 53 females) from grades 4, 6, and 8 completed a questionnaire examining their gambling behavior in general and individually played a computerized blackjack game with the following data being recorded: percentage of accuracy, amounts of money bet, gross winnings, percentage of wins, number of hands played, and end balance. Findings revealed few developmental differences in prevalence and frequency of gambling behavior and performance on a blackjack task. Males were found to wager greater amounts of money and have larger gross winnings than females on the blackjack task. Furthermore, males were more likely to view gambling as involving both large amounts of skill and luck, thus suggesting an illusion of control for gambling activities. The results are discussed from a cognitive developmental perspective. PMID- 24233847 TI - Psychopathology in pathological gamblers seeking treatment. AB - High rates of psychiatric symptoms have been reported in pathological gamblers. This study of psychiatric comorbidity in pathological gamblers is the first to use structured psychiatric interviews assessing DSM-III-R Axis I and II disorders. The Structured Clinical Interview for DSM III-R (SCID-P, SCID-II) was administered to 40 (25 male, 15 male) pathological gamblers seeking outpatient treatment in Minnesota for gambling, and 64 (41 male, 23 female) controls. High lifetime rates of Axis I (92%) but not Axis II (25%) psychopathology were found in pathological gamblers as compared to controls. No differences between male and female gamblers were found in rates of affective, substance use or personality disorders. Females had higher rates of anxiety disorders and histories of physical/sexual abuse. Possible associations between psychiatric disorders and pathological gambling are discussed along with gambler typologies and implications for future research. PMID- 24233848 TI - Gender, gambling and problem gambling. AB - With data from a 1989 Iowa survey (N=1,011), adult male and female respondents are compared on their problem gambling, its correlates, as well as their gambling behavior. Gambling behavior means its scope, frequency, wagering and leisure time spent at gambling. Women's gambling behavior was lower than that of men, due to their having a narrower scope of gambling behavior, but the genders were not significantly different on frequency, wagering and time spent at gambling. Women and men did not differ significantly on problem gambling. Problem gambling is measured as loss of control over gambling, and consequences due to gambling as well as gambling behavior. Women and men did differ significantly, however, on several predictors of problem gambling. Women's estrangement from a conventional lifestyle and integration into a social world of gambling appeared to help explain their problem gambling. Alcohol consumption appeared to be a more important predictor for men than women. The genders shared the attitude that the odds can be beat as well as being big spenders as predictors of their problem gambling. The results are interpreted with practitioners' efforts to prevent and treat problem gambling in mind. PMID- 24233849 TI - The effect of metals and ammonia on SO2 oxidation to sulphates in the ambient air. AB - The effect of metals and ammonia on the relationship between mass concentrations of sulphur dioxide and sulphate in the air was studied near an aluminium plant over a 1-year period. Sulphur dioxide, sulphates and ammonia in the air as well as metals (Pb, Fe, Mn, Zn, Cu, Cd and Al) in the deposit were measured at four measuring sites.The levels of mass concentrations of SO2 were low at all measuring sites while the levels of mass concentrations of sulphates in the air and concentrations of metals in the deposit were high. The levels of ammonia were found to decrease in relationship to the distance from the source of pollution.The relationship between the mass concentrations of sulphate and SO2 can be described by the equation y=ax (b) ;where y is the percentage of sulphate sulphur in the total sulphur (sulphate and SO2) and x is the mass concentration of the total sulphur in the air. The values of the coefficients a and b are characteristic of individual areas.As the results show the coefficients a and b obtained at a measuring site close to the plant and outside the urban area are characteristic of an industrial area. At control sites in the urban area the coefficients are characteristic of an urban area. At the measuring site close to the industrial zone and the centre of the urban area the interaction of the effects occurs. Therefore, the coefficient a is characteristic of an urban area and b of an industrial one. PMID- 24233850 TI - The status, distribution and ecology of wildlife on the U.S. Doe Hanford Site: A historical overview of research activities. AB - Since the inception of the U.S. DOE Hanford Site in 1943, numerous studies have been conducted on terrestrial wildlife. Onsite contractors have focused their attention on the role of wildlife in the uptake and transport of radionuclides. Graduate students from across the nation have also completed more than 15 theses on wildlife. This paper discusses the past history of wildlife research at Hanford and the individual species of wildlife that have been observed at Hanford. Forty species of mammals, 187 species of birds, 3 species of amphibians and 9 species of reptiles have been documented on the Hanford Site to date. PMID- 24233851 TI - The variability and significance of selenium concentrations in Shorebird feathers. AB - The selenium distribution in the flight feathers of a marine wader, the Oystercatcher (Heamatopus ostralegus), is investigated. In the wing the highest concentrations are found in the outer primaries, notably primary 8. The inner tail feather exceeds the primary 8 concentration. Whithin the vane of a single feather, the highest concentrations are found in the tip, the lowest at the basis of the feather. The results are discussed in relation to the use of the feather as an indicator of selenium exposure.In comparing marine wader species shortly after completion of the feather growth, a negative relation is found between the fresh primary 8 vane concentration and body weight of the species. A functional role of selenium in respect to the metabolic rate is suggested. PMID- 24233852 TI - Environmental characteristics in oligotrophic waters: Data evaluation and statistical limitations in water quality studies. AB - Standard statistical tests of nutrient variability in the euphotic layer of an oligotrophic system in the S.E. Aegean Sea were performed. Practical problems resulting from data handling, such as high errors associated with low concentrations, nonlinearity and interaction among variables were examined. The practical problems in the analysis of environmental data, arising from statistical limitations were considered: linear correlations between chlorophyll alpha and nutrients were found to be significant only for ammonia, and the multiple regression model was found to be of limited value as a tool for a description of the system. By contrast, principal component analysis contributed significantly to the interpretation of each variable. The difficulties arising from the use of statistical methodology, and particularly the limited goodness-of fit of the regression models, are discussed in relation to the suitability of oligotrophic waters as 'control sites' in eutrophication studies. PMID- 24233853 TI - A simple and fractal analysis of the European on-line network for airborne radioactivity monitoring. AB - We introduce two simple descriptors and use the fractal dimension to characterize the capability of a monitoring network to either 'spot', 'delineate' or 'track' a pollution cloud moving across a territory. The descriptors are applied to the 'European' monitoring network for radioactive aerosol (i.e. the sum of the national networks). Simple analysis shows that on average the time and space resolution of the network are well balanced for tracking the movement of a radioactive cloud. Such tracking, however, can only be started one or two days after the release. The geographical inhomogeneity of the network is quantified by a fractal dimension of 1.6, implying that radioactive clouds with a dimension less than 0.4 might not be detected by the network. PMID- 24233854 TI - Comparative evaluation of procedures for the determination of PAH in low-volume samples. AB - The aim of this investigation was to evaluate a simplified version of an HPLC method for the determination of PAH in suspended particles collected from small air volumes indoors, outdoors or in personal exposure measurements. The simplification consisted in: (a) collecting PAH by low-volume samplers; (b) extracting PAH ultrasonically; and (c) omitting separation of interfering substances before analysis by HPLC. The results show that the introduction of these modifications affords a considerable reduction in analysis time and solvent expenditure, without affecting the quality of measurement. PMID- 24233855 TI - Indian Society of Gastroenterology. PMID- 24233860 TI - Nursing and genetic health care. AB - Advances in DNA technology are leading to major developments in nursing practice in clinical genetics, including the creation of new roles for nurses who care for people with genetic conditions. Application of genetic information and testing is moving genetics into the mainstream of health care. Therefore, it is anticipated that nurses in all areas of practice will become involved in the provision of information about genetic testing and assisting individuals and families in decision making and adjustment to new genetic information. This article provides an overview of the profession of nursing which may be useful to genetic counselors in the development of collaborative relationships between the two professions. PMID- 24233861 TI - A retrospective survey of community based utilization of Tay Sachs screening in Eight New Jersey counties. AB - The purpose of this study was to determine the rate of utilization of Tay Sachs disease screening by the Ashkenazi Jewish population. Pregnant women who were referred to one of three genetic centers in New Jersey for amniocentesis unrelated to Tay Sachs screening were the study population. 4490 charts were reviewed retrospectively to determine the at risk population for Tay Sachs disease (Ashkenazi Jews) and whether or not patients and their spouses had elected Tay Sachs screening prior to referral. A group of 25 patients who did not elect screening were questioned as to their specific reason for declining Tay Sachs screening. Overall community utilization was 90%. Of the couples who did not elect screening, 64% felt that their risk to have an affected child was too small, 16% could not recall Tay Sachs screening being offered to them, 8% felt that screening was inconvenient. Tay Sachs screening as a voluntary preventive health care program has a high utilization rate in our study group. PMID- 24233862 TI - Training Genetic Counselors to provide teratogen counseling. AB - Provision of teratogen counseling requires acquisition of knowledge and skills from several disciplines. Traditionally, training in teratogen counseling has occurred "on the job." We describe a formal, didactic and experiential curriculum for teratogen counseling as an integral part of the Graduate Program in Genetic Counseling leading to the master of science degree at Northwestern University. All students complete a 5-week rotation with the Coordinator of the Illinois Teratogen Information Service (TIS). This provides them with an opportunity to evaluate a spectrum of teratogen exposures, to interpret teratogen studies in a manner useful for patients, and to develop skills in assessing and addressing psychosocial issues associated with fetal exposure to potential teratogens. Students also learn first hand about how a TIS functions and when and how to refer to TIS specialists. The goal of the program is to provide genetic counseling students with the opportunity to gain experience in accessing and interpreting teratology research and in communicating teratogen information to patients and health professionals in a sensitive, effective manner. PMID- 24233863 TI - Niflings are nephews and nieces. PMID- 24233864 TI - Historical origins of pedigree charts. PMID- 24233865 TI - Proximal fractures of the humerus in patients older than 75 years of age: should we consider operative treatment? AB - BACKGROUND: Over 75 % of patients presenting with a proximal humerus fracture are 70 years or older. Very little is known about the outcome after operative treatment of these fractures in very old patients. This study was performed to gain more insight in safety and functional outcome of surgical treatment of proximal humerus fractures in the elderly. MATERIALS AND METHODS: In this observational study, we analyzed all operatively treated patients, aged 75 or older, with a proximal humerus fracture between January 2003 and December 2008 in our center. Patient selection was on clinical grounds, based on physical, mental, and social criteria. Complications were evaluated. We used the DASH Questionnaire to investigate functional outcome, pain, and ADL limitations. RESULTS: Sixty-four patients were treated surgically for a displaced proximal fracture of the humerus: 15 two-part, 32 three-part, and 17 four-part fractures. Mean DASH scores were 37.5, 36.9, and 48.6, respectively. Regarding the operative methods, overall good results were obtained with the modern locked plate osteosynthesis (mean DASH 34.4). Prosthetic treatment, mostly used in highly comminuted fractures, often resulted in poor function (mean DASH 72.9). Persistent pain and ADL limitations were more present in more comminuted fractures (64 and 50 % in patients with 4 part fractures vs. 14 % in 2-part fractures). There were no postoperative deaths within 3 months of surgery, and fracture-related and non-fracture-related complication rates were low (non-union 3 %; 1 myocardial infarction). CONCLUSION: This study shows that it is safe and justifiable to consider surgical treatment of a severely dislocated proximal humerus fracture in selected patients aged 75 and older. LEVEL OF EVIDENCE: According to OCEBM Working Group,Level IV. PMID- 24233866 TI - Testing the effectiveness of the project success summer program for adult dyslexics. AB - The major purpose of this study was to test the effectiveness of the Project Success Summer Program (PSSP) for adult dyslexics. Using a pretest-posttest one group design, the experimenter examined the effects of PSSP's intensive eight week program on the reading and spelling test scores of subjects (n=63). Data analysis indicated subjects' reading and spelling scores improved significantly in five areas: reading of real words, passage reading rate, reading comprehension, spelling, and phoneme deletion. A second purpose of the study was to determine the best predictors of reading comprehension from among the study's eight pretest reading and spelling measures. Regression analysis revealed that passage reading rates and individual word reading rates were the best predictors of reading comprehension scores. Interpretation of the results of this study suggest that training in phonological skills can improve poor readers' basic decoding skills resulting in improved reading rate, comprehension and spelling. PMID- 24233867 TI - The effects of multisensory structured language instruction on native language and foreign language aptitude skills of at-risk high school foreign language learners. AB - Research findings suggest that most students who have foreign language learning problems have language-based difficulties and, in particular, phonological processing problems. Authors of the present study examined pre- and posttest scores on native language and foreign language aptitude tests of three groups of at-risk high school students enrolled in special, self-contained sections of first-year Spanish. Two groups were instructed using a multisensory structured language (MSL) approach. One of the groups was taught in both English and Spanish (MSL/ES), the other only in Spanish (MSL/S). The third group (NO-MSL) was instructed using more traditional second language teaching methodologies. Significant gains were made by the MSL-ES group on measures of native language phonology, vocabulary, and verbal memory and on a test of foreign language aptitude; the MSL/S group made significant gains on the test of foreign language aptitude. No significant gains on the native language or foreign language aptitude measures were made by the NO-MSL group. Implications for foreign language classroom instruction of at-risk students are discussed. PMID- 24233868 TI - The impact of an intensive multisensory reading program on a population of learning-disabled delinquents. AB - The high prevalence of learning disabilities in the juvenile delinquent population has been well documented, but attempts to remediate and have an impact on recidivism of this population of delinquents has produced limited results. The present study is a replication of the remediation phase of the 1976 LD/JD Project with methodological refinements to control for treatment integrity and strength of treatment. Delinquents in two detention facilities were screened for a developmental reading disorder. Subjects were selected for the study based on normal intelligence, full English proficiency, and a discrepancy of 15 points between reading achievement and IQ. Subjects in the treatment group received 90 minutes of remedial reading instruction per day using a multisensory (Orton/Gillingham) approach. A comparison group received 45 minutes of daily reading instruction in the regular classroom. There was no significant difference between the two groups in mean age of first arrest, mean age, and mean hours of reading instruction. Based on pre- and posttesting in reading and arrest records one year following release, the treatment group made significantly greater growth in reading (.33 year growth vs -.05 year growth per 10 hours of instruction) and had a significantly lower rate of recidivism (41 percent vs 63 percent) than the comparison group. Results were discussed in terms of hours of instruction necessary to improve reading, intervening treatment variables, and cost effectiveness of remedial program. PMID- 24233869 TI - Case study of language and numerical disability: A sequential processing deficit? AB - We report a case study of Christine, an intelligent 30-year-old woman with a developmental learning disability. Psychometric evaluation and extensive interviews revealed several findings: most notably, evidence of anomia, auditory processing problems, difficulty acquiring reading and spelling skills, and an extremely poor sense of number. In addition, Christine showed all four of the Gerstmann symptoms (left-right confusion, finger agnosia, dysgraphia, and dyscalculia). We suggest that most, if not all, of these impairments may be explained in terms of a sequential processing deficit (e.g., Bakker 1967; Tallal 1980). In Christine's case, difficulty perceiving serial order appears to have resulted in a major conceptual impairment involving number.HD-To me four is a number that comes after three and before five. It means twice two ...C-To me four is a picture. PMID- 24233870 TI - Successful applications of montessori methods with children at risk for learning disabilities. AB - The critical elements in the Montessori philosophy are respect for the child, individualization of the program to that child, and the fostering of independence. With her research background, Maria Montessori devised a multisensory developmental method and designed materials which isolate each concept the teacher presents to the child.In presenting these materials the teacher observes the concept and skill development level of the child, ascertaining areas of strength and weakness and matching the next presentation to the child's level of development. Using small sequential steps, the teacher works to ameliorate weakness and guide the student to maximize his strengths. These presentations, usually initiated by the child, enhance cognitive growth using a process which integrates his physical, social, and emotional development.The curriculum contains four major content areas: Practical Life; Sensorial; Oral and Written Language; and Mathematics. Geography, History, Science, Art, Music, Literature, and Motor Skills are also included. In all of these the Montessori presentations build from the simple to the complex, from the concrete to the abstract, and from percept to concept. Vocabulary and language usage are integral to each presentation.The procedures introduced through these presentations are designed to enhance attention, increase self-discipline and self-direction, and to promote order, organization, and the development of a work cycle. At-risk children benefit from the structure, the procedures, and the curriculum. Applications of this method require more teacher selection of materials and direct teaching, particularly of language and math symbols and their manipulations.This early childhood intervention provides an individualized program which allows the at-risk child a successful experience at the preschool level. The program includes a strong conceptual preparation for later academic learning and it promotes the development of a healthy self-concept. PMID- 24233871 TI - The writing road to reading: From theory to practice. AB - Orton-based programs include essential elements that insure success for teaching language to regular and special education children. This paper traces the theoretical foundations of The Writing Road to Readingby Romalda B. Spalding (1990) from the beginning concepts taught Mrs. Spalding by Dr. Samuel T. Orton through its validation in current cognitive science and learning theory. Pilot project locations and success statistics with regular and special education children in Arizona, Louisiana, Maine, and Texas are presented. It explains how direct, multisensory instruction in seven processes necessary for skilled reading and principles of skill learning and instruction are incorporated in the Spalding Method. PMID- 24233872 TI - A future of reversals: Dyslexic talents in a world of computer visualization. AB - With the recent revival of visual approaches at the forefront of several scientific, mathematical, and technological developments, this paper proposes that visually oriented dyslexics may be in an increasingly favorable position in future years. The same set of traits which has caused them so much difficulty in traditional verbally-oriented educational systems, may confer special advantages in emerging new fields which rely heavily on visual methods of analysis-fields which employ powerful graphic workstations and supercomputers to visualize complex scientific data. Recent trends have also led some technical professionals to become aware that their own special talents seem to be closely associated with certain dyslexic traits. It is argued that similarly mixed talents have been major factors in the accomplishments of a number of important historical figures. PMID- 24233873 TI - Familial patterns of learning disabilities. AB - Extended families of 12 young adults (9 LD, 3 non-LD) were given a battery of tests and questionnaires, and 131 persons, ranging in age from 6 to 85, were classified as LD or non-LD on the basis of subtest scores 1 SD below the mean or less on subtests of the PIAT and WRAT achievement tests. Pedigree analysis indicated that LD was strongly familial, with the most probable mode involving a major gene effect, but the type of disability (reading/ math) was not directly inherited. Autoimmune disorders were significantly correlated (P<.005) with LD, especially in families in which LD remained a major handicap into adulthood, a trait that also varied between families. In two of the LD families, adults showed little evidence of the reading/spelling deficits they had shown when tested as children, while adults in other families failed to make gains in reading and spelling. PMID- 24233874 TI - Nonverbal learning disability, school behavior, and dyslexia. AB - The aims of the study were to investigate whether children showing a low nonverbal/high verbal (LNV) WISC-R profile are more likely to exhibit behaviors conducive to school failure than children with a low verbal/high nonverbal (LV) profile, and to examine the relationships among these behaviors, the LNV/LV profiles, and reading ability. The 65 subjects included 27 LNV and 38 LV children, aged 5 to 11 years. Results confirmed earlier findings (Badian 1986) that LNV children are perceived by their teachers as significantly poorer than LV children in many behaviors associated with school success. There was a dichotomy, however, between LNV good and poor readers. All LNV subjects displayed problems in organizational skills, but those who were dyslexic were poorer in social behavior (e.g., acceptance of criticism and peer relationships) than either LNV good readers or LV good or poor readers. It was concluded that children with a low nonverbal/high verbal profile and a probable right hemisphere dysfunction, who appear to be dyslexic in the early school years, are at high risk for both social behavior problems and school failure, and that these children are a more high-risk group than poor readers with a low verbal/high nonverbal profile. PMID- 24233875 TI - Object naming ability of adults with written language difficulties. AB - Several studies have observed that school-aged, reading-disabled children have object-naming problems. In addition, significant positive relationships between object-naming ability and reading and spelling skills have been observed for this population. The co-occurrence of these problems has been explained by common underlying phonological deficiencies. Because written language problems can persist beyond the school-aged years, the purpose of this study was to examine object-naming ability and the relationship between object naming and written language of adults. Twenty-two adults, half with written language difficulties and half without, performed four tasks: object naming, object recognition, reading, and spelling. Significant positive relationships were obtained between object-naming ability and reading ability, object-naming ability and spelling performance, and reading and spelling performance. In addition to phonological deficiencies, the results indicated that adult poor readers and spellers lack knowledge of the orthographic structure of words. These findings suggest that problems underlying object naming and written language do not resolve with cognitive maturation or additional years of experience with language and should be addressed in the early school-aged years. PMID- 24233876 TI - Syllable and rime patterns for teaching reading: Analysis of a frequency-based vocabulary of 17,602 words. AB - A frequency-based vocabulary of 17,602 words was compiled and analyzed in order to group words with recurring syllable and rime patterns for teaching reading. The role of the rime unit (e.g.,ite inkite andinvite) in determining vowel pronunciation was central to the analysis because of the difficulty that the ambiguity of English vowel spelling presents to children who do not learn to read words easily. Vowel pronunciation in each orthographic rime was examined, both for its consistency in all words in which the rime occurs and for regularity, defined as conformity to the most frequent pronunciation for each vowel spelling in each of six orthographic syllable types.Of the 824 different orthographic rimes, 616 occur in rime families as the building blocks of almost all the 43,041 syllables of the words. These rimes account for a striking amount of patterning in the orthography: 436 are both regular and consistent in pronunciation (except where a single exception word occurs); another 55 are consistent but not regular. Of the remaining 125, only 86 have less than a 90 percent level of consistency. The high order of congruence of orthographic and phonological rimes suggests their usefulness as units for teaching reading. PMID- 24233877 TI - Automaticity training for dyslexics: An experimental study. AB - Less-skilled readers may experience a processing bottleneck in reading comprehension produced by a failure to automate word recognition. The automaticity hypothesis predicts that training which increases rapid and automatic word recognition will improve comprehension. To date few studies have tested this hypothesis. Our goal was to test the automaticity hypothesis by training dyslexic readers (n=35) to access the meaning of words more rapidly. Training consisted of speeded word games implemented on a microcomputer that provided feedback concerning subjects' speed and accuracy using sound and graphics. Three experimental tasks were administered both before and after training in which trials with trained and untrained stimuli were randomly intermixed. The measures were latency and accuracy of word vocalization, sentence comprehension, and a dual-task procedure designed to measure automaticity. Although pre/post improvement was larger for trained than untrained stimuli, reaction time on the word vocalization and sentence comprehension tasks improved significantly for both trained and untrained stimuli. In contrast, automaticity and sentence comprehension accuracy improved significantly for trained but not untrained stimuli. The training effect in comprehension remained when controlling for increases in word knowledge. The results support the automaticity hypothesis and further suggest that severely disabled readers may benefit from training in automatic word recognition. PMID- 24233878 TI - Issues in phonological awareness assessment. AB - Awareness of the internal phonological structure of words is a causal factor in success with the alphabetic principle in word recognition. However, findings with the Lindamood Auditory Conceptualization (LAC) Test reveal 25-30% of the population show deficiency in a subtle component of phonological awareness termed comparator function. We argue that this comparator function-an ability to hold the phoneme and/or syllable segments of two phonological structures in mind and compare and represent any variations in the number, identity, or order of their segments-is a primary sensory-cognitive function underlying the secondary function of self-correction in word recognition and spelling. And since word recognition correlates highly with comprehension, comparator function also indirectly impacts this basic purpose for reading. We suggest that the needs of many individuals, including educators themselves, for development and refinement of phonological awareness/comparator function may be misdiagnosed and underaddressed unless more sensitive measures of phonological awareness are used. The consequence of inadequate assessment/remediation of these deficiencies in educators is that they may be less able to assess and address these deficiencies in their students. Standard phonics instruction is known to be ineffective in developing phonological awareness for many individuals. However, phonological deficits can be addressed both preventively and remedially using procedures that are fundamentally different from typical phonics instruction. PMID- 24233879 TI - Foreword. PMID- 24233880 TI - Hen ovomucoid-agarose: A new conjugate for the isolation by affinity chromatography of UDP-galactose: Glycoprotein galactosyl-transferase. AB - A new conjugate for the affinity chromatography of UDP-galactose:glycoprotein galactosyltransferase has been synthesized by coupling hen ovomucoid, a ligand similar to the acceptor substrate, to agarose.The hen ovomucoid-Sepharose conjugate binds galactosyl transferase more tightly that other acceptor-Sepharose conjugates.The new adsorbent gives comparable yields and purifications with those obtained by ligands similar to the nucleotide moiety of the substrate and to the "specifier" protein, alpha-lactalbumin.The soluble galactosyltransferase from rat ventral prostate is effectively removed from the high speed supernatant by an ovomucoid-Sepharose column. The enzyme can be eluted with buffer containing EDTA andN-acetylglucosamine in a high yield (75-80%) and in a purified form (4000-fold purification). The stability of ovomucoid to heat and to high concentrations of urea and its inhibition of some proteases makes the conjugate easy to operate with an quite useful even with rather crude preparations. PMID- 24233881 TI - Protection of immobilized sulfhydryl groups against autooxidation by alterations in their microenvironment. AB - Immobilized sulfhydryl groups were prepared by partial thiolation of NH2-glass beads. The microenvironment of the immobilized SH groups was varied by different chemical modifications of neighboring NH2 groups. Introduction of a strong charge in the surroundings of immobilized sulfhydryls results in their dramatic stabilization against autooxidation. This effect is due to the salting of O2 from the surface microlayer of the thiolated beads. PMID- 24233882 TI - Determination by the enzyme thermistor of cellobiose formed on degradation of cellulose. AB - A calorimetric assay procedure for the determination of cellobiose has been developed. The cellobiose is hydrolyzed by beta-glucosidase and the glucose formed is measured calorimetrically by an enzyme thermistor containing co immobilized glucose oxidase and catalase. The system was optimized with regard to the arrangement of the enzymes, the pH-dependence of the separate enzymic steps, and of the total system. By placing the beta-glucosidase in a precolumn that could be switched in and out of the flow through the enzyme thermistor, both cellobiose and glucose present in the sample could be determined. The performance with standard solutions and with crude samples from cellulose degradation experiments was investigated. PMID- 24233883 TI - Delayed luminescence of luminol initiated by a membrane-bound peroxidase. AB - The luminescense of the luminol-H2O2 system was initiated by either free or membrane-bound horseradish peroxideae (HRP). The instantaneous luminescene decayed rapidly and was followed by the delayed luminescence in the presence of excess luminol. The delayed luminescence was characterized by a chain reaction, in which luminescence intensity increased exponentially. Membrane-bound HRP demonstrated that the delayed luminescence took place even in the absence of HRP if the instantaneous luminescence was initiated by HRP. A mechanism for the nonenzymatic luminescence is proposed and discussed. PMID- 24233884 TI - Immobilization of proteins as a tool for studying primary structure around their cysteinyl residues. AB - The primary structure around the single cysteinyl residue of chicken pepsin was investigated by binding the protein via this residue to an insoluble carrier. Carriers stable towards reagents used for the fragmentation of proteins and sequence analysis were prepared by coupling a spacer arm to polyN-hydroxymethyl acrylamide using a thioether bond that is potentially cleavable by mercuric ions (1). Phenacyl bromide group, attached to the free end of the spacer, reacted rapidly and specifically with the cysteinyl residue of chicken pepsin. Up to 300 mg of the enzyme were bound to 1 g of carrier.The polymer-bound protein was cleaved by trypsin or by cyanogen bromide or by a sequence of both. Fragments of 40-120 amino acid residues, depending on the method of cleavage, remained attached to the polymer through the cysteinyl residue. The compositions and partial sequences of these fragments revealed that the cysteinyl residue is located within or in the vicinity of a loop in the molecule formed by a disulfide bond. PMID- 24233885 TI - Antidiatom activity of marine bacteria associated with sponges from San Juan Island, Washington. AB - Crude extracts of 52 marine bacteria associated with sponges, which were collected from the sea near San Juan Island, Washington, USA, were screened using diatom attachment assays against Amphora sp., Nitzschia closterium, Sellaphora sp. and Stauroneis sp. to investigate their antidiatom activities. Among these samples, five expressed strong anti-adhesion effects on all four tested diatoms. There was no negative effect observed from those five active samples on the growth of Amphora sp. Those five active samples were prepared from respective isolates, which all belonged to the genus Bacillus based on 16S rRNA gene sequencing analysis. The results of present study indicate that Bacillus may play important roles for sponges' chemical defence against biofouling of diatoms and that the metabolites of Bacillus may be a potential source of natural antifouling compounds. PMID- 24233886 TI - In search of consolidation of short-term memory in nonhuman animals. AB - Wixted (Annual Review of Psychology, 55, 235 - 269, 2004) has argued that forgetting is due to consolidation failure. Previous research with humans and nonhuman animals has reported evidence for consolidation in intermediate or long term memory (LTM). The present study examines whether consolidation occurs in short-term memory in pigeons. Delayed matching-to-sample accuracy was reduced when retroactive interference (an extraneous task in Experiment 1 or houselight illumination in Experiment 2) was interpolated in the retention interval. Accuracy was not greater, however, when interference occurred at the end of the retention interval, as compared with when it occurred at the beginning. That is, there was no evidence for consolidation in short-term memory for pigeons. We did find, however, the beginning-end effect originally reported by Roberts and Grant (Journal of Experimental Psychology: Animal Behavior Processes, 4, 219-236, 1978) and the recovery from forgetting reported by White and Brown (Journal of the Experimental Analysis of Behavior, 96, 177-189, 2011). The results are discussed in relation to temporal distinctiveness theory as an alternative to consolidation. PMID- 24233887 TI - Women's health funding. PMID- 24233888 TI - Protecting patients, society. PMID- 24233889 TI - Feeding the physician pipeline. PMID- 24233890 TI - TMA vs. Cigna. PMID- 24233891 TI - Good communication. PMID- 24233892 TI - Predictors of severe hypotension in neurocritical care patients sedated with propofol. AB - INTRODUCTION: Propofol is used extensively in neurocritical care (NCC) due to its pharmacologic properties allowing for facilitation of serial neurologic examinations. Despite widespread use, few studies have identified risk factors for hypotension in these patients. We aimed to determine predictors of hypotension in NCC patients sedated with propofol. METHODS: This retrospective, multicenter study evaluated 237 patients at two academic medical centers, both with dedicated NCC teams led by board-certified neurointensivists. Univariate analyses were performed to determine risk factors associated with severe hypotension during sedation with propofol. Multivariable analysis was performed to determine variables independently associated with hypotension, defined as a mean arterial pressure (MAP) less than 60 mmHg. RESULTS: There was an average maximum reduction in MAP of 28.8 % after propofol initiation in the entire cohort. Severe hypotension developed in 62 (26.2 %) patients to a median nadir MAP of 56 mmHg. Those who developed severe hypotension had a longer median duration of mechanical ventilation (5.0 vs. 3.6 days; p = 0.01) and an increased in-hospital mortality (38.7 vs. 24.0 %; p = 0.03). Multivariable logistic regression analysis identified increasing number of changes to the propofol infusion rate, baseline MAP 60-70 mmHg, and need for renal replacement therapy (RRT) as factors independently associated with hypotension. CONCLUSIONS: Multiple factors predicted hypotension in NCC patients receiving propofol. Clinicians should use propofol cautiously in patients with a lower baseline MAP or receiving RRT. Development of protocols related to the frequency of dose titrations is also recommended to prevent this avoidable complication. PMID- 24233894 TI - Cyclic changes in volatile constituents of bovine vaginal secretions. AB - Headspace gas chromatography was used to examine the volatile components of bovine vaginal secretions in three consecutive estrous cycles from each of four cows. Results indicated that there was an interesting peak with a retention of 2.7 min. It showed a successive rise and fall zero to three days before estrus. Gas chromatographic evidence and mass spectral data confirmed that this peak was acetaldehyde. Another unidentified compound with a retention time of 27 min was found to be unique to proestrus. It occurred two to three days prior to estrus, but was absent at any other time of the cycle. PMID- 24233893 TI - The impact of nonsteroidal anti-inflammatory drugs on inflammatory response after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: The degree of inflammatory response with cytokine release is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). Previously, we reported on an association between systemic IL-6 levels and clinical outcome in patients with aneurysmal SAH. The intention was to assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the inflammatory response after SAH. METHODS: Our method involved exploratory analysis of data and samples collected within a previous study. In 138 patients with SAH, systemic interleukin (IL-6) and c-reactive protein (CRP) were measured daily up to day 14 after SAH. The correlations among the cumulatively applied amount of NSAIDs, inflammatory parameters, and clinical outcome were calculated. RESULTS: An inverse correlation between cumulatively applied NSAIDs and both IL-6 and CRP levels was found (r = -0.437, p < 0.001 and r = -0.369, p < 0.001 respectively). Multivariable linear regression analysis showed a cumulative amount of NSAIDs to be independently predictive for systemic IL-6 and CRP levels. The cumulative amount of NSAIDs reduced the odds for unfavorable outcome, defined as Glasgow outcome scale 1-3. CONCLUSIONS: The results indicate a potential beneficial effect of NSAIDs in patients with SAH in terms of ameliorating inflammatory response, which might have an impact on outcome. PMID- 24233895 TI - Behavioral correlates for minor volatile compounds from stink bugs (Heteroptera: Pentatomidae). AB - Many terrestrial Heteroptera have small, but functional, dorsal abdominal glands as adults. The chemistry, and associated intra- and inter-specific behavior, for dorsal abdominal gland secretions from 10 species representing four genera of Pentatomidae was investigated. Eighteen volatile compounds were identified in species-specific blends from the dorsal abdominal gland secretions ofEuschistus, Acrosternum, andEurydema adults, including aliphatic, aromatic, and terpenoid constituents. Evidence from bioassays is presented that parasitic Tachinidae (Diptera) and Scelionidae (Hymenoptera) use these secretions as kairomones. A field experiment was performed to test the hypothesis that minor volatiles increase the specificity of the main pheromone component from NearcticEuschistus species, methyl (2E,4Z)-decadienoate. However, significantly fewer individuals ofE. tristigmus were captured in traps baited with the complete blend for this species than in traps baited with methyl (2E,4Z)-decadienoate alone. Thus, at the concentrations tested, these kinds of dorsal abdominal gland secretions may be epideictic, promoting spacing in the natural habitat. PMID- 24233896 TI - Structure-activity relationship observations for European corn borer moth pheromone and fluoro analogs via computer molecular modeling. AB - Structure-activity relationship (SAR) observations were made for theZ-type European corn borer moth pheromone, (Z)-11-tetradecen-1-ol acetate, and a series of analogs with fluorination in the alcohol portion of the molecule. The attractiveness of these analogs and the pheromone was compared to the electrostatic potential map of the molecular mechanics (MM) minimized lowest energy conformation for each compound. A critical range of electrostatic potential on the protons of the double-bond appears to be essential for optimal acceptor fit and attractiveness. PMID- 24233897 TI - Natural variation of toxicity in encrusting spongeCrambe crambe (Schmidt) in relation to size and environment. AB - The presence of intraspecific variation in toxicity and its relationship with biological or ecological factors were studied in the spongeCrambe crambe. Within specimen (periphery and central part), between-size (<1000 mm(2) in area, between 1000 and 10,000 mm(2) and >10,000 mm(2)) and between-habitat (well-illuminated and dark communities) variations in toxicity were evaluated by the Microtox bioassay. Quantitative differences were detected that were not attributable to within-specimen variation but to size and habitat effects. Habitat comparisons showed that sponges in the shaded habitat were significantly more toxic than those of the well-illuminated community. Sponges of the smaller size classes displayed significantly less toxicity than the medium-sized specimens. Results are interpreted under the optimal defense theory and their ecological implications are considered. PMID- 24233898 TI - N,N-dimethyluracil and actinidine, two pheromones of the ponerine antMegaponera foetens (Fab.) (Hymenoptera: Formicidae). AB - By means of gas chromatographic, mass spectrometric, and micro-preparative methodsN,N-dimethyluracil and actinidine were identified as two ethologically active compounds in the ponerine antMegaponera foetens. The synthesized poison gland compoundN,N-dimethyluracil released trail-following behavior, whereas actinidine, found in the pygidial gland, stimulated ants to leave the nest, possibly in an alarm reaction. Biological activity of the synthetic samples were confirmed by behavioral experiments and electroantennogram responses with worker antennae. PMID- 24233899 TI - Behavior of processionary males (Thaumetopoea pityocampa) induced by sex pheromone and analogs in a wind tunnel. AB - The behavioral response of processionary males (Thaumetopoea pityocampa) to the natural pheromone (Z)-13-hexadecen-11-ynyl acetate (1) and structurally related analogs in a wind tunnel is presented. Stereomerically pureZ-1 and a mixture with theE isomer in 80:20 ratio elicited similar attraction responses at 1 ug and higher. The activity was dose-dependent, being optimum at 1 ug with 90% and 80% of males contacting with the source in the presence of theZ-1 andZ/E-1, respectively. 11-Hexadecynyl acetate (2) functioned as a pheromone mimic, being able to induce the complete mate-finding behavioral sequence, although its activity was much lower than that of the pheromone. (Z)-13-Hexadecen-11-ynyl alcohol (3) and, particularly, (Z)-13-hexadecen-11-ynal (4) were potent inhibitors of the upwind flight response in mixtures withZ-1 in 99:1, 95:5, and 91:9 ratios. (Z)-1,1,1-Trifluoro-16-nonadecen-14-yn-2-one (5) also inhibited the response of males to pheromone, particularly in the source contact behavior. Comparison with activity displayed by analogs in field tests is also reported. PMID- 24233900 TI - Alkadienes mediating courtship in the parasitoidCardiochiles nigriceps (Hymenoptera: Braconidae). AB - Courtship inCardiochiles nigriceps (Viereck) (Hymenoptera: Braconidae) involves male attraction to females and male antennation of females followed by mounting and copulation. Once the female is located, antennation and mounting of the female are mediated by the hydrocarbon fraction of female's Dufour's gland and cuticle. The identification of the cuticular hydrocarbons of males and females revealed a mixture of alkanes and alkenes, in addition to a series of alkadienes specific to females. These female-specific alkadienes reported from Braconidae are unusual among insect alkadienes in that the second double bond occurs in the middle of the molecule. Bioassays with three available alkadienes revealed that contact behaviors (antennation and mounting) are in part mediated by the (Z,Z)-7, 13-heptacosadiene and at least one other alkadiene in combination with other hydrocarbons found in males and females. PMID- 24233901 TI - Modification of responses byCampylomma verbasci (Heteroptera: Miridae) to pheromone blends in atmospheres permeated with synthetic sex pheromone or individual components. AB - Trapping experiments were conducted in orchards to test the hypothesis that exposure of the mullein bug,Campylomma verbasci (Meyer), to atmospheres permeated with its synthetic sex pheromone, a 94:6 blend of butyl butyrate (BB) and (E) crotyl butyrate (CB), or BB or CB alone, would alter the pheromone responses of males toward off-ratio blends. Exposure to the natural 94:6 blend shifted the response preference away from the natural ratio to blends enriched in BB, including a 99:1 blend, which is normally significantly less attractive than the natural ratio. In an atmosphere permeated with CB, male mullein bugs were as responsive to blends containing 20, 33, and 43% CB, up to seven times the natural percentage, as they were to the 94:6 blend. In an atmosphere permeated with BB, responses to five blends ranging from 94:6 to 99:1 BB:CB were not significantly different, whereas in an untreated atmosphere blends of 98:2 and 99:1 were significantly less attractive than the 94:6 blend. Individual components appeared to disrupt pheromone communication primarily through the creation of a sensory imbalance and modified interpretation of pheromone blend ratios, whereas disruption by the complete pheromone blend apparently involves several mechanisms, including false-trail following and camouflage. Disruption of pheromone communication was most effective with the natural 94:6 sex pheromone blend. PMID- 24233902 TI - Isolation and identification of sex pheromone ofSymmetrischema tangolias (Gyen) (Lepidoptera: Gelechiidae). AB - The sex pheromone of the South American potato tuber mothSymmetrischema tangolias (syn.:Symmetrischema plaesiosema) was identified as a 2:1 mixture of (E,Z)-3,7 tetradecadien-1-ol acetate and (E)-3-tetradecen-1-ol acetate by means of dual column GC, EAG, GC-EAD, GC-MS, NMR, and wind-tunnel bioassays. (Z)-5-Tetradecen-1 ol acetate and (Z)-7-tetradecen-1-ol acetate were also identified in the pheromone gland extract. MaleS. tangolias were able to detect these acetates (EAG), but their addition to the two-component sex pheromone did not improve attractiveness. Field trials in Cajamarca and Cusco, Peru, showed that traps baited with the synthetic sex pheromone were able to catch large numbers of maleS. tangolias. PMID- 24233903 TI - Egg dispersion in codling moth: Influence of egg extract and of its fatty acid constituents. AB - Codling moth females (Cydia pomonella, Lepidoptera: Tortricidae) (CM) usually lay single eggs and have a tendency to disperse. In a first experiment we observed that single females exposed to 20 apples distribute their eggs regularly among apples, suggesting a dispersive oviposition behavior. In a dual-choice situation, isolated females avoided oviposition on areas of cardboard treated with a methylene dichloride egg extract at the dose of ca. 1.0 egg equivalent/cm(2). A strong avoidance was obtained in response to a 20-fold dose, which was accompanied by a significant reduction of total oviposition. Seven major compounds found by GC analyses in the methylene dichloride extract of 2 to 3-day old eggs were saturated or unsaturated C14-C18 straight-chain fatty acids: myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. This was confirmed by GC-MS analysis of an extract made by ethyl ether. Smaller amounts of three methyl esters were also identified as methyl myristate, methyl palmitate, and methyl stearate. A blend of the seven fatty acids (FA) mimicked rather well the avoidance provoked by the extract, and this avoidance was confirmed by choice between treated and untreated fruits by single females. The treatment of apples with the 7FA mixture induced an aggregative distribution of the eggs among apples. We also found that the amounts of fatty acids harvested in the extract depend on the egg age. Amounts of fatty acids increased until eggs were 4 days old and then decreased before hatching. In this paper we discuss the possible role of simple molecules, such as fatty acids and their esters, as semiochemicals indicative of juvenile tissues. PMID- 24233904 TI - Optical isomers of 3,13-dimethylheptadecane: Sex pheromone components of the western false hemlock looper,Nepytia freemani (Lepidoptera: Geometridae). AB - (3S, 13R)-3, 13-Dimethylheptadecane [(3S, 13R)-3, 13-dime-17Hy] is the major pheromone component of the western false hemlock looper (WFHL),Nepytia freemani. In comparative gas chromotographic-electroantennographic detection (GC-EAD) analyses of stereoselectively synthesized isomers, 1 pg of (3S, 13R)-dime-17Hy elicited significantly stronger electrophysiological responses by male WFHL antennae than did 1 pg of separately injected (3R, 13R)-, (3R, 13S)- or (3S, 13S) 3, 13-dime-17Hy. In field experiments with individually tested stereoisomers. (3S, 13R)-3, 13-dime-17Hy was the only stereoisomer to attract males, but the four-stereoisomer blend was 3.6 times more attractive. Quaternary and all binary combinations of (3S, 13R)-3, 13-dime-17Hy with the other stereoisomers were equally attractive, suggesting that synergisytic behavioral activity in WFHL resided with either one of (3R, 13R)-, (3R, 13S)-, or (3S, 13S)-3, 13-dime-17Hy. Because optical isomers of (di)methylhydrocarbons do not separate on currently available columns, it remains unknown whether female WFHL also produce a four stereoisomer pheromone blend. Substitutionality of pheromone stereoisomers without loss of behavioural activity has not previously been reported, but favorably compares with the concept of pheromone redundancy that was first suggested for the multiple pheromone component blend of the cabbage looper moth,Trichoplusia ni. PMID- 24233905 TI - Effects of DIMBOA on several enzymatic systems in Asian corn borer,Ostrinia furnacalis (Guenee). AB - By using spectrophotometric analysis and isoelectric focusing electrophoresis (IEF), we found inhibition of acetylcholinesterase (AChE), general esterase activity (Est), and lipase activity in larvae of the Asian corn borer (ACB),Ostrinia furnacalis (Guenee), fed on cabbage dipped in DIMBOA (400 ppm). Amylase was not influenced, while activity of cytochrome P-450 monooxygenase and glutathloneS-transferase was increased. The results indicate that DIMBOA influences activity levels of some nervous system and detoxication enzymes and inactivates some hydrolysis enzymes. PMID- 24233906 TI - Use of paired and single traps to assess perception and discrimination of sex pheromone mixtures in the field byTrichoplusia ni (Hubner). AB - Paired wind-oriented traps (WORT) and single traps were deployed simultaneously in the same field to investigate whether or not inferences about the central nervous system processes of discrimination and perception can be made from differences in moth captures. The stimulus levels deployed were those that typically may be found downwind of a calling virgin female cabbage looper,Trichoplusia ni (Hubner), so that inferences are relevant to natural stimulus intensities. Captures of male cabbage loopers in the WORT traps paralleled prior laboratory measures of pheromone mixture discrimination. The pattern of captures by the two trapping systems probably reflects perceptive and discriminative processing differences in the central nervous system. Captures in traps baited withZ7-12: Ac alone were equal to, or better than, captures in traps baited with three- and six-component mixtures that containedZ7-12: Ac. PMID- 24233907 TI - Chemical investigation of aggregation behavior ofTriatoma bugs (Hemiptera: Reduviidae). AB - Nymphs ofTriatoma infestans andTriatoma mazzottii are weakly attracted to their feces and to extracts of feces in polar solvents, but not to nonpolar solvent extracts. The major volatile compounds identified in feces by solvent extraction and thermal desorption wereo-aminoacetophenone, 4-methylquinazoline, and 2,4 dimethylquinazoline, but these showed no attractant activity at a range of concentrations. Choice tests with a moving current of air gave no positive reaction to feces, extracts, or pure compounds. PMID- 24233908 TI - Sequestration of lichen compounds by lichen-feeding members of the Arctiidae (Lepidoptera). AB - A survey for the presence of sequestered lichen compounds in 103 wild-caught imagines representing eight different genera and 16 different species of the Arctiidae was conducted. Known lichen compounds were detected for the first time in 24 of the analyzed specimens (representing five different genera and 11 different species) based on their HPLC retention times and on their UV-absorption spectra. The anthraquinone parietin, the depside atranorin, as well as a hydrolytic cleavage product of the latter were among the lichen compounds most frequently detected in wild-caught imagines. The observed variation of sequestered lichen compounds in wild-caught imagines with unknown feeding history may be due to several reasons. Lack of lichen compounds in imagines may have been caused, for example, by larvae feeding on lichens with no or only minute amounts of phenolic products. The age of the specimens analyzed may also influence the results obtained. Avoidance of lichen compounds by selective feeding on those parts of lichen thalli that have no or little lichen products may be another reason for the lack of lichen compounds in imagines. Preliminary feeding experiments conducted with larvae ofEilema complana, for example, indicated that the larvae fed exclusively on the algal layer and cortex of the lichenCladonia pyxidata, whereas the medulla, which is rich in fumarprotocetrarie acid, was avoided. As expected, imagines hatching from the larvae were free of this lichen compound. Any ecological role of the sequestered lichen compounds for the herbivores is unknown. It is possible, however, that sequestered lichen compounds may be utilized for the chemical defense of arctiid moths or against microbial pathogens. PMID- 24233909 TI - Optimization and phenotype allocation. AB - We study the phenotype allocation problem for the stochastic evolution of a multitype population in a random environment. Our underlying model is a multitype Galton-Watson branching process in a random environment. In the multitype branching model, different types denote different phenotypes of offspring, and offspring distributions denote the allocation strategies. Two possible optimization targets are considered: the long-term growth rate of the population conditioned on nonextinction, and the extinction probability of the lineage. In a simple and biologically motivated case, we derive an explicit formula for the long-term growth rate using the random Perron-Frobenius theorem, and we give an approximation to the extinction probability by a method similar to that developed by Wilkinson. Then we obtain the optimal strategies that maximize the long-term growth rate or minimize the approximate extinction probability, respectively, in a numerical example. It turns out that different optimality criteria can lead to different strategies. PMID- 24233910 TI - Preface/Editorial for the special issue. PMID- 24233911 TI - Prevalence studies of problem gambling in the United States. AB - The rapid expansion of legalized gambling in the United States has produced tremendous demands for information about the number and characteristics of problem gamblers in the general population. This paper examines the results of prevalence studies of problem and pathological gambling that have been carried out in the United States. The discussion is largely chronological, with a focus on comparative findings from the 15 United States jurisdictions where prevalence studies have been completed since 1980. The results of diese studies verify findings from clinical and experimental studies as well as suggesting important avenues for future research. The paper concludes with a consideration of the role played by survey research in advancing the field of gambling research. PMID- 24233912 TI - The prevalence of pathological gambling in Canada. AB - This paper critically reviews prevalence estimates of problem and pathological gambling in Canada. Populations studied are adults, adolescents and primary school children. The proportions of pathological gamblers found in Canadian studies (ranging from 1.2% to 1.9% for adults) are similar to prevalence rates reported in the United States. Given the apparent link between gambling availability and increases in the prevalence of problem and pathological gambling, it is hoped that provincial and federal authorities in Canada will make investments in research and treatment of pathological gambling in the future. PMID- 24233913 TI - The New Zealand national survey of problem and pathological gambling. AB - In New Zealand, awareness of gambling-related problems has increased in association with the legalization of new forms of gambling. This paper presents the methods and selected results from a national survey of gambling and problem gambling completed in New Zealand in 1991. While the primary aim of the study was to determine the extent of problem gambling in New Zealand, the study included a second phase intended to assess the validity and reliability of the widely-used South Oaks Gambling Screen as well as to examine other aspects of problematic involvement in gambling. The results of the two-phase study in New Zealand show that problem gamblers in different countries are remarkably similar in demographic terms as well as with regard to other risk factors associated with problematic gambling involvement. The New Zealand study of problem gambling points the way toward important research topics that will require further exploration in the future. PMID- 24233914 TI - Estimating the extent and degree of Gambling related problems in the Australian population: A national survey. AB - A stratified random doorknock method was used to interview 2744 respondents in four state capitals in Australia. The interview was in 3 parts with the latter two only administered to regular, once per week or more often gamblers (N=290). The measures completed by this group included the South Oaks Gambling Screen and a range of psychological measures. A conservative interpretation of the results was that "problem gamblers," defined in terms of a range of personal and interpersonal gambling-related costs, comprised 1.16% (+/-0.34%) of the Australian population. It was estimated that problem players' losses may account for about one quarter of all expenditures on gambling. PMID- 24233915 TI - Prevalence surveys of problem and pathological gambling in Europe: The cases of Germany, Holland and Spain. AB - In the 1960s and 1970s, many European countries legalized several forms of gambling, especially slot machines, lotteries, casinos and bingo, in order to control illegal gambling and to obtain tax revenues for government. In this paper, we examine the status of research on problem and pathological gambling in three European countries: Germany, Holland and Spain. The results of the studies as well as the relationship between these studies and the expanding gaming industries, attitudes toward gambling in the general population, and the regulation and control of gaming in each country are discussed. PMID- 24233916 TI - Estimating the prevalence of adolescent gambling disorders: A quantitative synthesis and guide toward standard gambling nomenclature. AB - This article reviews the extant published and unpublished studies that estimate the prevalence of adolescent gambling problems in North America. The nine nonduplicative studies identified by our literature search included data collected from more than 7700 adolescents from five different regions of the United States and Canada. In addition to comparing the conceptual and methodological differences that exist among these studies, this article employed a meta-analytic strategy to synthesize prevalence estimates from the existing studies. This analysis revealed that within a 95 percent confidence interval, between 9.9% and 14.2% of adolescents are at risk of developing or returning to serious gambling problems. Similarly, between 4.4% and 7.4% of adolescents exhibit seriously adverse compulsive or pathological patterns of gambling activity. Finally, the discussion proposes a generic multi-level classification scheme to reconcile the divergent classification methods and data reporting strategies. This new multi-level approach to reporting gambling prevalence will facilitate interstudy comparisons among existing estimates of gambling prevalence and help to provide a general data reporting system for future research. PMID- 24233917 TI - Prevalence studies and the development of services for problem gamblers and their families. AB - Where funded by government, prevalence studies have typically led to the development of services for problem gamblers and their families. Such assessments of the need for services have been seen as the appropriate political response to growing expressions of concern about problem gambling that often follow moves to legislate for an increasing range of gambling products. This theme is apparent for Australia, Canada, New Zealand and the United States. In this paper, initiatives in these different jurisdictions are briefly summarized and tabulated. PMID- 24233918 TI - The prevalence of problem and pathological gambling: A critical analysis. AB - Prevalence of pathological gambling refers to the percentage of cases of pathological gambling occurring in the community at a given time. Prevalence studies conducted in different principalities throughout the world are reviewed, and it is found that none of them conforms to this definition of prevalence. The major error in all but the most recent surveys conducted is identified as the use of questions which ask whether gambling-related problems have ever occurred rather than whether they are currently occurring. This error will lead to an over estimation of the prevalence of pathological gambling in society. The second major error identified in nearly all studies involves the accuracy of the screens being used to assess whether or not an individual is a pathological gambler. Concerns about the efficiency of the South Oaks Gambling Screen have not yet been satisfactorily resolved. None-the-less, the widespread use of the South Oaks Gambling Screen has made a valuable contribution to international comparisons of prevalence studies. Future work that explores the emerging relationship between levels of personal expenditure on gambling, types of gambling product and gambling-related problems are recommended. PMID- 24233920 TI - Chromatographic techniques for pollution analyses. AB - Pollution studies of air and water samples have been greatly enhanced by the use of chromatographic techniques. The selection of the proper detectors coupled with the various column types and substrates have broadened the capabilities of environmental analyses. Proper care in sampling protocols and sample treatment has steadily improved the sensitivity of these measurements. The recommended methods for air, wastewater, drinking water and solid waste samples all utilize some type of chromatographic analysis for the determination of organic contaminants. Three complimentary techniques: i.e., headspace sampling (dynamic and static methods), microextractions (liquid-liquid and/or liquid-solid) and solid-phase extractions have expanded the capabilities of such studies to permit the analytical chemist to perform fast in-the-field monitoring, concentrate low levels of analytes and determine solubilities of toxic substances. A discussion of other environmental areas which should be studied, along with the changes and/or modifications in analytical technology which should be investigated, will be presented. PMID- 24233919 TI - Validity and responsiveness of the EQ-5D and the KIDSCREEN-10 in children with ADHD. AB - BACKGROUND: The aim of our study is to compare the validity of a generic preference-based Quality of Life (QoL) instrument for adults to that of a generic child-specific QoL instrument in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHODS: EQ-5D and KIDSCREEN-10 data were collected using a questionnaire survey performed among parents with a child or adolescent diagnosed with ADHD. The measurements were compared to assess (dis)similarities of the instruments' constructs and responsiveness to different health states. Principal component analysis (PCA) with varimax rotation was used to identify factors underlying the constructs of both instruments. Instruments' index scores of respondents with different treatment and comorbidity profiles were compared using Student's t tests. Cohen's effect sizes were calculated for an indirect comparison of the instruments' responsiveness and discriminating ability. Separate analyses were performed in children aged 8-12 and 13-18 years. RESULTS: A strong relation was found between the EQ-5D and KIDSCREEN-10 index scores. However correlations between EQ-5D and KIDSCREEN-10 items were moderate or low. The PCA identified five separate factors of quality of life. A physical and a mental factor included a combination of three EQ-5D dimensions and six KIDSCREEN-10 items; the remaining EQ-5D and KIDSCREEN-10 items constituted complementary factors without any overlap between the separate instruments. Scores of both instruments differed significantly according to respondents' response to treatment and comorbidity profile. Cohen's effect sizes indicated comparable results of the instruments' responsiveness and discriminative ability. CONCLUSIONS: The results highlight that the instruments measure different constructs of QoL in children with ADHD. Despite this, the analyses showed comparable responsiveness and discriminative ability of the instruments. These results suggest that for economic evaluations, the EQ-5D is an appropriate and valid instrument for measuring QoL in children. PMID- 24233922 TI - The effect of oxygen addition on the determination of cadmium and lead in blood and foods by graphite furnace atomic absorption spectrometry. AB - It is well known that in the analysis of low temperature vaporized metal elements such as cadmium and lead, a high ashing temperature causes a loss of the target atoms at the ashing stage, while low ashing temperature causes incomplete decomposition of organic components in the sample. In order to solve these problems, the effect of oxygen addition on determination of cadmium and lead in blood and foods was studied. Oxygen was introduced into the atmosphere in the graphite furnace at the beginning of ashing stage for 20 seconds at 0.5 l/min. Relation between ashing temperature and sensitivity was examined, and the oxygen addition minimized signal depression by the sample matrix. It can be concluded that the addition of oxygen at the ashing stage not only reduces the background absorption, but also suppress the volatilization of target atoms at the ashing stage by the formation of their oxides. PMID- 24233921 TI - Separation of large polycyclic aromatic hydrocarbons in particulate matter by liquid chromatography. AB - The level of mutagenic activity of particulate polycyclic aromatic hydrocarbons (PAHs) is highly dependent upon structure, so that similar isomers can range from being very active to totally inactive. The suitability of GC/MS or LC with single wavelength absorbance or fluorescence monitoring, coupled with the availability of standards, has resulted in emphasis being placed on the small PAHs (five or fewer rings).In the work reported here, LC was coupled to a computerized photodiode array detector. The former separated the components in a diesel particulate matter extract and the latter spectrally differentiated the large PAHs (more than 24 ring-carbons). Since each PAH has a characteristic UV/VIS absorbance spectrum, each generated a unique pattern of absorbance maxima and minima. Computerized pattern recognition techniques were then used to investigate quantitative structure-activity relationships of the PAHs as predictors of carcinogenicity.The chemical profile of a series of unsubstituted PAHs, for which carcinogenic data was available, was represented by 17 descriptors of the reactivity and properties of those PAHs. Using this data set, the properties of another series of PAHs were found to be consistent with their reported carcinogenicity. PMID- 24233923 TI - An optimization procedure for the isocratic high-performance liquid chromatographic separations of environmental pollutants. AB - This paper describes the use of the overlapping resolution mapping procedure to optimize the separation of priority pollutants by isocratic, reversed-phase high performance liquid chromatography. Three classes of pollutants are considered: polycyclic aromatic hydrocarbons, substituted phenols and phthalate esters. The procedure requires only seven chromatographic runs for each set of pollutants before an optimized mobile phase composition is derived which can satisfactorily resolve all the components in the respective mixtures of pollutants. The main advantage of such a systematic scheme to optimize mobile phase compositions is an improvement in method development times compared to conventional techniques. Another benefit is that expenditures on solvents are reduced. PMID- 24233924 TI - Some applications of Freon-22 in supercritical fluid chromatographic analysis of environmental pollutants. AB - The applications of Freon-22 (R22) as a mobile phase and as a modifier in supercritical fluid chromatography were investigated. For the purpose of this investigation, the separation of eleven phenols listed by the United States Environmental Protection Agency as priority pollutants was studied. It was found that the use of neat R22 greatly reduced the retention times of the phenols compared with the use of neat carbon dioxide as mobile phase. Satisfactory separation of all the eleven phenols could be achieved using 5% R22 as modifier in carbon dioxide. The promising results obtained in this preliminary investigation indicate the potential for the use of R22 in supercritical fluid separation processes. PMID- 24233925 TI - Identification of residual pesticides in water by GC/QPMS. AB - The extensive use of the broad range of pesticides employed to maintain golf courses has prompted serious environmental concerns in Japan since courses tend to be located in mountainous regions, often in close proximity to virgin water sources. Since older empirical methods are not appropriate for substance identification and determination of substance concentrations on the ppb order, gas chromatographyquadrupole mass spectrometry (GC/QPMS) can be employed. A simple extraction of 500 ml of drainage pond water gives a sample which allows identification of pesticides with quantitation on the ppb order using selected ion monitoring (SIM). A sample of drainage pond water from a golf course revealed fenitrothion, funitrothion, chlorothalonil and isoprothiolane in concentrations of 120.1, 20.7, 45.6 and 130.5 ppb, respectively. PMID- 24233926 TI - Direct coupling of supercritical fluid extraction-supercritical fluid chromatography for the determination of selected polycyclic aromatic hydrocarbons in aqueous environmental samples. AB - A rapid and simple method is described for the quantitative determination of polycyclic aromatic hydrocarbons in aqueous environmental samples. A microscale on-line supercritical fluid extraction-supercritical fluid chromatography system using carbon dioxide is employed. The extract is analysed using capillary supercritical fluid chromatography with UV detection. Detection was carried out at 254 nm. An extraction efficiency of as high as 91% was obtained for the PAHs. PMID- 24233927 TI - Separation of selected PAHs by using high performance capillary electrophoresis with modifiers. AB - The effect of varying SDS concentration in a micellar electrokinetic capillary chromatographic system (MECC) is investigated. In addition, the introduction of gamma-cyclodextrin as modifier to the electrophoretic medium, containing SDS and a phosphate-borate buffer, is shown to give satisfactory separation of the seven selected PAHs. The separation efficiency is increased with the addition of gamma cyclodextrin. PMID- 24233928 TI - Optimization of the gradient HPLC separation of selected phthalates using the overlapping resolution mapping technique. AB - Optimization procedures for the reversed-phase separations of six phthalates using the isoselective multisolvent gradient elution (IMGE) system are described. A systematic experimental design has been employed to gather retention data on the compounds in a mixture. The data were then fitted into a second-order polynomial equation and an overlapping resolution mapping (ORM) technique of data analysis was subsequently used to establish the optimum solvent mixture for the highest resolution of all adjacent peaks in the chromatogram. PMID- 24233929 TI - Analysis of priority substituted phenols by micellar electrokinetic chromatography. AB - The use of micellar electrokinetic capillary chromatography (MECC) for the separation of eleven substituted phenols listed by the United States Environmental Protection Agency as priority pollutants was demonstrated. The effects of the pH and ionic strength of the buffer, and the length of the separation column on resolution were investigated. The retention characteristics of the eleven phenols in MECC are discussed. PMID- 24233930 TI - Incineration of hazardous wastes. AB - Glaxo has practiced incineration of liquid and gaseous wastes for over twenty years and currently operate eleven liquid and gas incinerators in the United Kingdom and Singapore. The liquid incinerators burn, as their main streams, those solvents that cannot be recovered and recycled within the processes. The early installations were for readily combustible solvents only. However, there has been a progressive move into the destruction of more difficult and hazardous wastes, with the consequential requirements for more sophisticated technology, in the belief that the responsible destruction of waste should be tackled near to its source. The eventual aim is to be self-sufficient in this area of waste management. The incineration of hazardous liquid and gaseous waste has presented a series of design, operational and monitoring problems into account which have all been successfully overcome. The solutions take into account the environmental consequences of the operations from both liquid and gaseous emissions. In order to ensure minimal environmental impact and safe operation the best practicable technology is employed. Environmental assessment forms part of the process development and permitting procedures. PMID- 24233931 TI - Environmental management in Singapore. AB - From modest beginnings, Singapore rapidly developed its industrial base which today comprises high technology and high value added industries. Economic growth was accompanied by a comprehensive housing and urban development programme.The formation of the Ministry of the Environment and the Anti-Pollution Unit in the early seventies marked Singapore's commitment to protect the environment in the face of rapid developments.Together with the rapid industrialisation, housing and urban development programme, Singapore also implemented a programme to prevent pollution as well as to control pollution from those sources which cannot be prevented.The success of these programmes is evident today and we have an environment that compares well with that of any nation in the world. PMID- 24233932 TI - Catalytic CO oxidation over manganese-containing perovskites. AB - Mixed metal oxides are discussed as possible substitutes for noble metals in automobile catalytic converters. The catalytic activity for CO oxidation of LaMnO3 and La0.5Sr0.5MnO3 catalysts was examined.The ability of these catalysts to provide lattice oxygen and to sustain the oxidation reaction, even in the absence of molecular oxygen, has been confirmed. Measurements were performed of the reversible oxygen uptake on the two catalysts. PMID- 24233933 TI - Water purification with magnetic particles. AB - CSIRO (Commonwealth Scientific and Industrial Research Organization) has for some years carried out research into more efficient ways of purifying water and wastewater. More intensive processing has been achieved by the use of finely divided solid reagents which can be regenerated and reused. The age-old problem of quickly separating the very small particles of loaded reagent from the accompanying liquid has been solved by utilizing a magnetic reagent in the form of magnetite, Fe3O4. A water clarification process is fully developed for the production of potable supplies from low quality ground and surface waters, with five plants in operation or under construction in Australia, the United Kingdom and Taiwan. The method has been extended to the removal of heavy metals from tailings dams, which has also reached full-scale with a plant near Canberra, to other industrial effluents, and more recently to sewage treatment. Successful pilot plant studies of the latter in Melbourne and Sydney have led to the decision to carry out a large-scale trial at Malabar, near Sydney. PMID- 24233934 TI - Entrapping of organic wastes by coordination clathrates. AB - The feasibility of the Hofmann clathrates Ni(CN)2(NH3).G(G=guest molecule) and the octahedral Werner-type complexes Ni(X)2(L)4 (X=NCS, NCO, CH3CO2, C6H5CO2; L=Py, 4-Mepy) as a scavenger for organic substrates in a polluted aqueous or organic medium is dependent on the complex lability, thermal stability and reversibility in solvent trapping which can be conveniently studied by thermogravimetric means. Besides the parent monomeric octahedral complexes, all the thermal decompositional intermediates, namely, monomeric tetrahedral, dimeric octahedral and polymeric octahedral, are also potential scavengers for selected organic substances though they operate via a cycle of bond-making and bond breaking processes. PMID- 24233935 TI - In search of a recyclable sulphur dioxide sponge-a new look at an old system. AB - The sulphur dioxide content and thermal stability of the quinol-SO2 clathrate have been studied by thermogravimetric analysis (TG), its derivative (DTG) and differential scanning calorimetry (DSC). These analyses demonstrated the thermal recoverability of the quinol from the clathrate and hence its potential use as a sponge for SO2 present in the environment as a pollutant. Similarly, Bu4N(+)I(-) was found to occlude NO2 and SO2 at 50 degrees C in solution. PMID- 24233936 TI - Leachate of fly ash derived from refuse incineration. AB - For highly urbanized cities where there is a scarcity of land available for landfilling, incineration of refuse is a feasible solution for solid waste disposal. After incineration, about 20% by weight of fly ash and other residues are produced and disposed of by landfill. Leachate tests carried out on samples of fly ash show that the heavy metal concentrations of the leachate are in excess of the permissible limits set by WHO. Lime and cement are used to stabilize the fly ash. The concentrations of heavy metals in the leachates of lime and cement treated fly ash are non-detectable. In additional to pollution control, the lime and cement treated fly ash significantly improves the properties of soft clay. PMID- 24233937 TI - Mercury contamination-what we have learned since Minamata. AB - Atmospheric cycling of mercury and other pollutants has become a major concern as industrialized countries have eliminated point discharges, sometimes by relocating the industries to underdeveloped and developing countries where point sources have become problems. Such circumventions may be to no avail in the long run as pollution continues to elevate levels of methylmercury in fish in waterways that are remote from direct contamination as well as where the source can be readily identified. Much has been learned about the cycling of mercury in the environment since human disabilities and deaths at Minamata, Japan, initially drew attention to the problem of methylmercury poisoning from the consumption of contaminated seafood in the 1950s. In that instance, methylmercury produced industrially concentrated to toxic levels in fish. As this manufacturing process was not used outside Japan, concern did not become immediate in other developed nations until the 1960s when it was established that mercury was not only biomethylated by microorganisms but also biomagnified through the food chain. Point sources to the waterways may have been eliminated too late to return the levels in fish to background because of the geochemical cycling of mercury through the environment. Despite decreases in domestic, industrial and agricultural point source releases over the last two decades, large quantities from non-point sources such as fossil fuel combustion, smelters, and incinerators are still being released. Much of this mercury is transported from the atmosphere to aquatic ecosystems and stored in sediments until it is again released to the water and atmosphere. PMID- 24233938 TI - The legal control of chlorofluorocarbon and halon substances in Hong Kong. AB - The Ozone Layer Protection Ordinance was recently enacted in response to Hong Kong's international obligations under the 1987 Protocol on Substances that Deplete the Ozone Layer. Commencing July 1 1989, chlorofluorocarbon production and consumption in Hong kong will be frozen at 1986 levels. A further reduction in two stages to 50% of 1986 levels will be implemented by 1999. The production and consumption of halon substances will also be frozen at their 1986 levels from January 1 1992. The Ozone Layer Protection Ordinance seeks to reduce the consumption and production of ozone depleting substances by a system of quota allocations. Importers of scheduled chlorofluorocarbons will need to be registered with the Environmental Protection Department. Only registered persons will be issued an import or export licence. Many practical problems remain in giving effect to the Protocol. The Protocol does not initially prohibit the export of scheduled substances to countries who are not parties to its provisions. However, commencing January 1 1993, a series of trade restrictions will be brought to bear on countries who are not parties to the Protocol. Graduated sanctions include: a ban on exporting prohibited substances to non member countries; a total prohibition against importing items containing controlled substances from non-member states; a prohibition against exporting technology or equipment used in the production of such substances. The Protocol has major implications for Hong Kong. In the first place it must find a suitable substitute for controlled substances in various manufacturing processes. In addition, as almost 100% of Hong Kong's re-exports of chlorofluorocarbons and halon substances are to non-signatory countries, there will be implications in giving full effect to the provisions of the Protocol in that regard as well. PMID- 24233939 TI - The effectiveness of composite lining systems in controlling the leakage of leachate from sanitary landfills to groundwater. AB - Leachate, the hazardous liquid that percolated through the refuse layers of a sanitary landfill, if it leaks through the landfill lining system, can become a serious source of groundwater pollution. In the past, leaks have been detected in many landfills lined with flexible membrane liners (FML) whose failure may be attributed to flaws such as imperfect seaming, rips, and tears of the membrane, or from chemical attack that dissolves the membrane. Recent studies have shown that composite lining systems which include either a clayey subbase or a layer of geotextile in addition to the FML, can substantially reduce the leakage of leachate. Therefore in this study, four different lining systems are proposed and evaluated to determine their effectiveness in controlling leachate flow under various degree of flaws (referred to as leakage fraction LF) in the FML. The Hydrologic Evaluation of Landfill Performance (HELP) computer model of the Environmental Protection Agency of USA, currently the most widely accepted model for predicting the performance of leachate collection systems in that country, is used to evaluate the following lining systems: (1) a single FML or liner, (2) a single FML with a clayey composite, (3) a single FML with a geotextile called Claymax, and (4) a double FML. Based on the climatic conditions and the present lining construction cost of Alaska, the study shows that a single FML or liner is the most economical but it is also the least effective in controlling leachate flow. Design (3), a single FML with a geotextile, costs about 50 percent more but it reduces the leakage of leachate by several orders. Design (2) is also effective but the cost incurred in constructing a 3 feet thick clayey subbase is prohibitive and thus to effectively and economically minimize the hazards of potential groundwater contamination by leachate, Design (3) is recommended as the composite lining system for future landfill sites. PMID- 24233940 TI - Factors affecting the leaching of lead from UPVC pipes. AB - This paper summarizes the results of a series of studies on the various factors that affect the leaching of lead from unplasticized poly(vinyl chloride) (UPVC) pipes. Factors that were studied include temperature, pH and extractants. Results showed that, for a given UPVC pipe, the rate of leaching of lead depended primarily on temperature and the nature of extractants. While the rate of leaching of lead was quite low with distilled water, it was very much enhanced by the presence of low concentration of anions such as Cl(-), HPO inf4 (sup2-) HCO inf3 (sup-) , NO inf3 (sup-) , SO inf4 (sup2-) and EDTA. EDTA, being a strong complexing agent, was most effective. Rates of leaching were found to be higher at elevated temperature except in the cases of HPO inf4 (sup2-) and EDTA. Effect of pH was not pronounced. The temperature at which the UPVC pipes were extruded was found to affect the rate of leaching of lead. Pipes extruded at 190 degrees C were found to have lower rate of leaching than those extruded at 180 degrees C and 170 degrees C. Analysis of the pipes by Scanning Electron Microscopy showed that the distribution of lead in the pipes extruded at 190 degrees C was more uniform than those extruded at 170 degrees C. PMID- 24233941 TI - Poly(sodium acrylamidoalkanoates) in water treatment. AB - Poly(sodium 6-acrylamidocaproate), poly(sodium 11-acrylamidoundecanoate), poly(sodium 11-N-methylacrylamidoundecanoate) and poly(sodium 11-N ethylacrylamidoundecanoate) have been synthesized. The performance of these anionic polyelectrolytes as coagulant aids in water treatment was assessed by the jar test. The effects of polymer dosage and pH on their performances were investigated in order to establish the optimum flocculation conditions. The effectiveness of these polyelectrolytes as well as a commercially available cationic polyamine organic coagulant aid was compared in terms of floc size, settling rate and the quality of treated water. Poly(sodium 6-acrylamidocaproate) and poly(sodium 11-acrylamidoundecanoate) were superior to poly(sodium 11-N methylacrylamidoundecanoate) and poly(sodium 11-N-ethylacrylamidoundecanoate), and they are as effective as the commercial cationic coagulant aid. PMID- 24233942 TI - Atmospheric acidification in the Asian region. AB - Atmospheric acidification in the Asian region is discussed from the perspectives of currently available regional measurements, and the knowledge now available from several decades of acidic deposition research in the northern mid-latitudes. The main conclusions emerge: (1) that there is insufficient information currently available to enable a quantitative assessment of the present state or future potential for atmospheric acidification across the whole region; and (2) that within the limitations imposed by (1) the possibility of future acidification in certain areas cannot be ruled out if economic development and energy use on a per capita basis evolve to the levels of the major industrial countries. These two conclusions point to the need for systematic, multidisciplinary studies covering the whole region. The studies should assess quantitatively the current levels of acidic and alkaline emissions (both natural and anthropogenic) to the atmosphere, identify the relevant chemical transformations and transport/deposition pathways in the regional atmosphere, and assess the susceptibility of regional plants, soils and groundwaters to acidification. PMID- 24233943 TI - Improving the living environment of Singapore. AB - For the past quarter century, the government of Singapore has redeveloped the city with multiple objectives. The city should be free of squatters, slums and pollutive influences. It should be clean, green and healthy for living. All necessary infrastructures are provided and function well. All the necessary building floor spaces are available to facilitate the daily needs of the people and to enhance economic growth.While all of these objectives should be kept and augmented, the city must now update its position and even give added attention to the quality of the living environment, visual and otherwise, in order to make Singapore a tropical city of excellence. This paper attempts to review the past achievements and outline the approaches envisaged for the near future. PMID- 24233944 TI - The new environmentalist. AB - This paper looks at the increasingly complex problems which face physical planners in the urban environment and considers the type of training required in the future for those who have to advise the government of the day on physical planning matters.Using the examples of planning problems which have been experienced in Hong Kong and Saudi Arabia, an analysis shows that they fall into three main categories: (a) physical problems (b) social problems, and (c) visual problems.It is considered that the conventional professionals do not possess the necessary basic training skills to deal with these problems as a whole, nor to discover the hidden opportunities. This is particularily relevant in the context of the growing 'green' debates which are becoming of increasing importance worldwide.As populations grow, the demand from pressure groups for scarce land resources will become more and more intensive. Singapore may face these problems because the government whishes to increase the population from 2(1/2) to four million.In conclusion it is considered that we shall need a new type of environmental planner in the future. This environmentalist should have a basic training in the earth sciences, the social sciences and the visual arts. PMID- 24233945 TI - Proposals for the conservation of nature in urban Singapore. AB - The benefits of conserving nature in urban environments have proved to be a significant factor in improving the quality of life for residents of major cities throughout the world. In Singapore there are still many potential areas in which conservation management techniques would support sufficient natural habitat and attract a wide diversity of wildlife.This paper attempts to establish the criteria for selecting such areas, to identify the numerous human needs to be satisfied and to describe several case study examples. PMID- 24233946 TI - Microplankton bloom in a brackish water lagoon of Terengganu. AB - Increased primary plankton productivity was observed in a brackish water lagoon of Terengganu during the study period between January 1988 to December 1988. The lagoon is also the site for the fish cage culture activities of sea bass during the study period. An examination of water quality at the sampling stations during the study period indicated that both the organic and inorganic nutrients were high during the pre-monsoon period. The source of the nutrient in the lagoon was believed to be derived from the agro-based industrial effluents, fertilisers from paddy fields as well as untreated human and animal wastes. This coincided with the peak production of plankton in the surface waters of the brackish water lagoon. During this period both cultured and indigenous fish species were seen to suffer from oxygen asphyxiation (suffocation due to lack of oxygen). The primary productivity values ranged from 9 to 22 MUg/L/h during the peak period while the microplankton species were composed of diatom, flagellates and dinoflagellates. Reduction in the primary productivity values were obtained with reduction in sallinity, specially during the peak monsoon months (November to March) corresponding to the Northeast monsoon period. PMID- 24233947 TI - Temporal variation in a coral reef community at Pattaya Bay, Gulf of Thailand. AB - Changes in the fringing coral reef community of a small island (Ko Nok) at Pattaya Bay, Gulf of Thailand, were examined at the beginning and at the end of a 3-year period using 7m*7m permanent quadrats for benthic organisms, and visual census along 100m transects for fish. The coral community was dominated by Porites lutea in terms of colony number and areal cover throughout the period. Variations in the community structure parameters on opposite sides of the island indicated increasing dissimilarity with time. Little variation in live coral cover was noted, but colony number and species diversity declined on both sides. The abundance of edible fish species dropped while that of non-edible species increased over the 3-year period, indicating selective removal of the former category through fishing. Impacts from both human and natural influences are implicated in these changes. PMID- 24233948 TI - Water quality planning and management for Dapeng bay, China. AB - The pollution sources around the Dapeng bay and the current water quality of the bay are presented. Two-dimensional mathematical models for modelling the tidal flow and pollutant concentration fields have been developed and used to predict the water quality impact generated by coastal economic development of the area. Water quality planning for the bay is conducted and some managerial measures for environmental protection are put forward. The results show that at present there is minimal pollution, and the water quality is good. If the region around the bay is to be developed as proposed, it would have minor impact on the marine water quality. The aim is to have the water quality higher than that of Class II standard in National Marine Water Quality Standard of China (NMWQSC). In order to maintain the present condition of the bay, the ecological equilibrium around the bay must be preserved. PMID- 24233949 TI - Ecology of marine fouling organisms at Eastern Johore Strait. AB - Marine biofouling causes problems to marine structure and obstructs condenser tubes in cooling systems which use sea water as the coolant. The main purpose of this study is to investigate the seasonal ecology of biofouling organisms such as the green mussel, Perna viridis, the dominant fouling species in the Eastern Johore Straits at the Senoko Power Station. The spawning time and its relationship with environmental conditions were studied. The physical, chemical and biological conditions of the sea at Senoko were monitored for a year. Settling slides were used to study the fouling succession in different monsoon seasons. The study showed that there were two main spawning peaks for the green mussel and that these peaks occurred during the intermonsoon months of November and April. These peaks were also correlated with the bimodal patterns for salinity, dissolved oxyen, bivalve veliger larval density and total plankton biomass of the Eastern Johore Strait water. Succession patterns were similar during the two monsoon seasons, however, the rate of fouling was probably greater during the southwest monsoon months. It is therefore advisable that the control or reduction of biofouling in Eastern Johore Strait should take into account the seasonal fluctuations and spawning of the fouling organisms. PMID- 24233950 TI - DNA adducts as early bioindicators of chemical exposure. AB - Sensitive analytical methods indicate the presence of hundreds of chemical contaminants in our environment. However, concentration of these pollutants is usually at the low parts per million or parts per billion level. At such low levels, toxicants induce long-term (chronic) rather than short-term (acute) toxicities. Experiments are designed to evaluate chronic toxicity using early bioindicators. Recently, fish have been used as experimental animals because some species show early (weeks as opposed to years in other research animals), sensitive responses. Thus, medaka (Oryzias latipes), following exposure to diethylnitrosamine (DEN), exhibited liver tumors in several weeks; more interestingly its DNA was modified (to a 'DNA-adduct') after only 24-48 hours exposure. Such adducts show promise as early bioindicators because they are formed within hours of exposure. The formation of DNA-adducts were monitored in medaka and rainbow trout (Salmo gairdneri) exposed to DEN by aqueous or intra peritoneal routes. Using HPLC-Fluorimetry, O (6)-ethylguanine (O (6)-EtGua) was detected and monitored in acid thermal hydrolysates of DNA isolates. (Detection limit for O (6)-EtGua was as low as 3 ng, 1.7*10(-11) moles). Fourier transform cyclotron resonance mass spectrometry with IR laser desorption/ionization was used advantageously to establish the structure of nucleotides, bases and nucleosides directly, without further cumbersome derivatizations. Other aspects of DNA-adducts are discussed. PMID- 24233951 TI - Some gaseous pollutants in Nakorn Sri Thammarat. AB - Three gaseous pollutants, carbon monoxide, nitrogen dioxide, and sulfur dioxide were studied in the Nakorn Sri Thammarat Province area (Thailand) during March August 1987. Air samples were taken from 12 stations covering four districts, i.e., Tungsong, Pakpanang, Muang, and Kanoum. Five stations are located in areas of light traffic conditions and low human population and seven are in densely populated areas with heavy traffic conditions.In this study the concentrations of pollutants found were in the range of non-detectable-0.7 ppm for carbon monoxide, 0.6-7.4 pphm for nitrogen dioxide, and non-detectable-7.4 pphm for sulfur dioxide. PMID- 24233952 TI - Management and control of pollution in Inner Johore Strait. AB - Coastal waters in South Johore, Malaysia are polluted to various degrees. The major pollution sources are domestric wastes from human settlements, agro-based wastes from palm oil mills and rubber processing factories, industrial effluents from industrial estates and discharges from animal farms. These pollution problems have adversely affected resources such as fisheries, recreational potential as well as the general aesthetic quality of the coastal environment particularly the Inner Johore Strait. Hence proper management and control measures are urgently needed to protect and further enhance the water quality to ensure environmentally sustainable development. This study examines various management options to control the pollution in the Inner Johore Strait. The options involve partial opening as well as complete removal of the Causeway to improve the tidal flow for more effective dilution and dispersion of pollutants. Computer simulation models are used to assess the impacts of the proposed options. PMID- 24233953 TI - A feasibility study for appraising recreational water quality in a Southeast Asian beach complex. AB - In a case study involving preliminary investigations for the feasibility of a beach resort complex in the west coast of Sarawak, Malaysia, since the acceptable quality of recreational water quality had not been specified, existing international standards and practices were reviewed to arrive at acceptable microbiological and physicochemical parametric levels. Water samples were collected on a weekly basis in the proposed beach complex at Tanjong Batu Coastal Reserve and also along the nearby Sungei Batang Kemena and its estuary. It was ascertained that the swimming water quality was acceptable in terms of faecal Coliforms, temperature, pH and dissolved oxygen. However E. Coli counts did indicate a potential risk of 1.68% for gastrointestinal illness and the ubiquitous presence of faecal Streptococci pointed to recent pollution of human or animal origin. Besides, grease and oil contents exceeded the WHO Guideline values. It was hence recommended that an appropriate sanitation or pollution survey should be carried out in the adjacent coastal catchment area and the beach. Also routine water sampling should be undertaken. Such action will help to pinpoint sources of pollution and lead to antipollution measures, thus helping to upgrade swimming water quality and establish swimming water quality standards. PMID- 24233954 TI - Diurnal models of traffic-generated CO for Penang, Malaysia. AB - Georgetown of Penang, an old city, is noted for its narrow streets. The existing traffic dispersal system is utterly inadequate to cope with the ever increasing number of cars and motorcycles on the road. The principal objective of this study is to build prediction models of CO to be employed as one of the planning tools in the future design of Penang urban traffic dispersal system. This study involves the monitoring of kerbside CO levels at selected sites and the fitting of hourly-averaged CO data to linear regression models incorporating the residual effect of CO emission due to traffic in the earlier periods and also different categories of vehicles. The best overall regression model appears to be the one based upon the total traffic count of motorcycles. This can be accounted for by the fact that the traffic counts of motorcycles and cars are highly correlated in most cases and that the emissions of CO from motorcycles are more readily detected as they travel closer to the kerb. The inclusion of residual CO in the models significantly improves the correlation coefficient from about 0.4 to about 0.7. PMID- 24233955 TI - Non-radiological contaminants from uranium mining and milling at Ranger, Jabiru, Northern Territory, Australia. AB - Protection from the hazards from radioactivity is of prime importance in the management of uranium mine and mill wastes. Such wastes also contain non radiological contaminants (heavy metals, acids and neutralising agents) which give rise to potential long-term health and environmental hazards and short-term hazards to the aquatic ecosystem, e.g. as a result of release of waste water. This study seeks to identify non-radiological contaminants (elements) transferred to waste water at the Ranger uranium mine/mill complex at Jabiru, which are likely to hazardous to the aquatic environment.The two principal sources of contaminants are: (i) ore and waste rock mobilised from mining; and (ii) process reagents used in the milling and mineral extraction process. These substances may or may not already be present in the natural environment but may lead to deleterious effects on the aquatic environment if increased above threshold levels.Rhenium, derived from the ore body, was found to be significantly enriched in waste water from Ranger, indicating its suitability as an indicator element for water originating from the mining and milling process, but only uranium, likewise derived from the ore, and magnesium, manganese and sulfur (as sulfate) from the milling process were found to be significant environmental contaminants. PMID- 24233956 TI - Environmental and biological monitoring of methyl ethyl ketone (MEK). AB - This study was conducted to evaluate the usefulness of various biological parameters for monitoring of workers exposed to methyl ethyl ketone (MEK). Fifty male workers from a large magnetic videotape factory participated in this study. Personal air samples were collected using 3M organic vapor monitors and analysed for MEK by gas chromatography with flame ionisation detector (FID). 10 mL of urine; blood (1 mL) and exhaled air were also collected at the end of an 8-hour workshift. The headspace GC method was applied for measurement of urinary and blood MEK. MEK in expired air was analysed directly by using a GC/FID.The correlation coefficients (r) between environmental MEK and all other biological parameters measured show significant positive relationships. The r for environmental MEK and urine MEK was 0.84; for blood 0.73 and for breath 0.64. The correlation coefficients between blood and urine was 0.72; blood and breath was 0.88 and urine and breath 0.60. These findings suggest that measurements of unmetabolised MEK in blood, exhaled air and urine can be used for biological monitoring of MEK exposure. Nevertheless, laboratory methodological assessment is in favour of measuring urinary MEK as it is non-invasive and does not have to be analysed immediately after collection. PMID- 24233957 TI - The determination of chlorofluorocarbons and extractives in the expanded and disposable polystyrene ware. AB - Residual chlorofluorocarbons (CFCs) and water-extractive residues in expanded polystyrene ware were determined because of the threat to environmental and public health arising from the ozone depleting potential of CFCs and the leaching of toxic monomers and oligomers into food and drink. Chlorofluorocarbon in expanded polystyrene ware was analysed using headspace gas chromatography in the flame ionization mode, and confirmed by gas chromatography-mass spectrometry. The amount of extractive residue leached from this type of polymeric material was determined using an aqueous medium simulating categories of food and beverages. A wide range of concentrations of CFC-12 (dichlorodifluorocarbon) was detected in the styrofoam ware. It fluctuated between a low of 32 ppm and a high of 35471 ppm in two different samples of styrofoam plates. Similarly, the highest and lowest levels of extractive residue detected in two different styrofoam plates were 54 ppm and 0.5 ppm respectively. CFC-22 or HCFC (chlorodifluorocarbon) was absent from these expanded polystyrene ware. The continued use of chlorofluorocarbons as a blowing agent will further exert a deleterious effect on the stratospheric ozone layer. Though the level of water extractive residue from these expanded polystyrene ware was relatively safe, public health could be further safe-guarded through improvmeents in raw material selection and mode of production. PMID- 24233958 TI - Phenolic water pollutants in a Malaysian River basin. AB - Phenolic chemicals with their very low taste and odour thresholds, high persistence and toxicity, are of growing concern as water pollutants. The compounds are known to exist in raw water as well as in treated water. The level of phenolic priority pollutants in water within the catchment area of the Linggi River Treatment Plant in Negeri Sembilan, Malaysia, which includes the Linggi river basin, was monitored. The 4-aminoantipyrin colourimetric method was used to determine total phenols whereas capillary column gas chromatography was used to determine the individual compounds. The results show that at most sampling stations, particularly those within the Seremban municipality, the level of phenols was found to exceed the recommended Malaysian standard of 2.0 MUg/L(-1) for raw water. This is seen as the direct impact of industrial and urbanization of the area and clearly indicates the unhealthy state of the Linggi river. The results also indicate the need to improve the water quality if the river is going to be used as a source of raw water. PMID- 24233959 TI - Lake destratification and speciation of iron and manganese. AB - A long-term study of the effect of artificial aeration (destratification) of a water storage dam upon the speciation of iron and manganese in the dam waters has been undertaken. Separation of dam samples into soluble and insoluble forms by selective membrane filtration was undertaken before using the techniques of EPR spectroscopy, ion chromatography and gel filtration to assess the speciation of soluble species, and selective extraction and surface analysis (ESCA, SIMS and SEM) techniques to determine the speciation of particulate iron and manganese species. The percentages of soluble iron and manganese before (1983-85) and after (1986-88) artificial aeration are compared for the periods Jan-Dec, Jan-Mar, and Jun-Aug at three depths 6 m, 15 m and 0.5 m above the dam base, to assess the importance of seasonal changes in the various depths of the dam. Although aeration had an initial marked reduction in levels of soluble iron and manganese at all depths of the dam, the concentrations of these mtals showed a steady increase over succeeding years. Analysis of the figures over summer and winter periods shows that the reduction of soluble iron was maintained in summer, but not during winter. Upon aeration, the initial reduction of soluble manganese concentration was maintained in succeeding years in the epilimnic regions of the dam, but not in the hypolimnion. Statistical analysis of data has been undertaken to correlate the changes in relationship between the various forms of iron and manganese with the advent of aeration. PMID- 24233960 TI - Quality of stormwater runoff from an urbanised watershed. AB - A field monitoring network was set up within the Stamford canal watershed in 1989 to study both the quantitative and qualitative aspects of storm runoff from this urbanised catchment. The data acquisition equipment comprised a continuous recording rain gauge, a water level recorder and an automatic water sampler capable of sampling storm runoff at preset intervals during rainfall events. Water samples were collected after each storm and laboratory tests were carried out on the physical and chemical properties of the storm water. Preliminary findings on the temporal variations of stormwater quality during single storms and the effects of antecedent dry weather period on the quality are presented. The average ranges of some of the significant quality parameters found in the storm runoff were also established. The quality of storm runoff from the catchment under study was found to be of an acceptable level and could potentially be developed as a water catchment area. PMID- 24233961 TI - The distribution of organic matter in songkhla lake basin (SLB). AB - The concentrations and the distribution of organic matter in SLB (e.g. the outer part of Thale Sap Songkhla area) were examined during the period of September 1988 to September 1989. Organic matter in water samples were analyzed by gravimetry. Total organic matter and dissolved organic matter concentrations ranged from 74 to 7908 mg/L and from 23 to 7813 mg/L, respectively. Except for a set of observations which showed low concentrations during the flood season in November 1988, organic matter was regularly distributed throughout SLB. Domestic effluent and aquaculture are hypothesized as major sources of organic matter contamination. The levels of organic matter concentrations in SLB are significantly higher than would be expected for an area considered to be uncontaminated. The data also indicated a linear relationship between concentrations of suspended organic matter and suspended solids. This may be due to the organic matter associated with suspended solids. PMID- 24233962 TI - Analysis of pesticide residues in Peninsular Malaysian waterways. AB - The use of organochlorine pesticides has caused concern due to their effects on human health and the Malaysian aquatic ecosystem, particularly so in view of their persistent and bioaccumulative properties. Since the extent of organochlorine pesticide pollution in Malaysian waterways is unknown except for isolated instances, a systematic survey has now been carried out. Water samples from various rivers were extracted, cleaned up with Florisil and analysed for the individual organochlorine pesticides by gas chromatography (GC) with an electron capture detector (ECD). DDE, DDT and heptachlor were present in all the river water samples of the west coast of Peninsular Malaysia. Other organochlorine pesticides were also identified from the water samples. However, the levels of all these are still below criteria values for Malaysian aquatic life, indicating that organochlorine pesticide pollution is less of a problem than other organic or inorganic pollutants. PMID- 24233963 TI - A study of the heavy metal concentrations of the Singapore River. AB - The concentrations of lead, cadmium, copper, zinc, iron, and mercury in the water, sediment and biota of the Singapore River were determined. The concentration of the various metals in water showed significant variation at different sampling times and there was enrichment of lead content. The spatial patterns of metal distribution in the sediment could be due to the different pollution sources such as exhaust emission from boats and other environmental variables such as clay content of sediment or tide level. In the biota, higher amounts of metals were found in species inhabiting the river bed while organisms of higher trophic level such as free-swimming fishes and crabs accumulated lower amounts. In general, the flesh of fishes and crabs had the least content of metals compared to other tissues. The Concentration of various metals in bivalve, Mytilopsis sallei, which were found extensively in the river did not reflect the pollution distribution. PMID- 24233964 TI - Wind flow in an urban environment. AB - The wind environment at ground leven in built-up areas is influenced by the extremely complex interaction amongst incident wind, mean vertical velocity gradient, turbulence and the shapes, sizes and layouts of building. Random layout of buildings could generate zones of overspeed and vortices in the connecting passage way between buildings, terraces, opensided shelters, courtyards, which could potentially cause unpleasantness, hazard from resuspended particulates, and airborne rain penetration into the buildings. The paper presents the results of two case studies comprising field measurements made within the Kent Ridge Campus, National University of Singapore, using DANTEC 54N10 Multichannel Flow Analyser and Probes. Results are presented in terms of non-dimensional windspeed coefficients. It is concluded that there is significant increase in windspeed due to channel and venturi effects. This information provides useful guidelines for building plans and layouts to the architects and engineers. PMID- 24233965 TI - Uptake, distribution and immunotoxicological effects of mercury in mice. AB - The uptake and distribution of mercury in various organs and tissues of mice were examined after administration with mercuric chloride (HgCl2) or mercuric sulphide (HgS). The results show that mice treated with HgCl2 were found to have significantly higher levels of mercury in various organs and tissues as compared to HgS-treated animals. Except for the kidneys, no significant differences were found in mercury levels between the HgS-treated and control mice. This appears to be due to the higher solubility of HgCl2, allowing for its greater absorption into the body. Irrespective of the mercurial administered, the kidneys contained the highest concentration of mercury, followed by the liver and brain. Mercury was also found to confer protection against Trypanosoma evansi, possibly due to its toxicity. When treated with HgS, enhanced antibody production and increased levels of circulating leucocytes was seen. HgCl2 and HgS-treated mice showed no signs of anorexia, no significant changes being found in growth and food intake. PMID- 24233966 TI - Noise surveys of hand-held pneumatic rock drills in Hong Kong. AB - A study of the noise generated by hand-held pneumatic rock drills at 15 road works locations in Hong Kong was conducted in 1989. The locations of road construction works were identified over one week period. Sound pressure levels (SPL) and band frequency analysis were measured with the integrated sound level meter at the level of the operator's ears. The sound levels for all 15 operators exceeded the local statutory limit of 90 dBA. The average sound level was 107.4 dBA and the corresponding continuous equivalent level adjusted to 8 hours or L eq (8h) was 104.8 dBA. The sound levels for the octave frequencies from 125 Hertz to 8000 Hertz were all in excess of 90 dBA. Estimates of the risk of developing hearing impairment for conversation speech among the operators were 18% and 42% after 5 and 10 years of exposure, respectively. Although there is adequate statutory control to restrict and reduce the hazards caused by noise at road construction works to the workers and to the public at large, no noise control measures were noted at the work sites and none of the operators used hearing protection. This situation was compounded by the short-term nature of road works and the high mobility of the operators. PMID- 24233967 TI - Major factors of industrial noise-induced hearing loss in Hong Kong. AB - A tripartite participation of government, trade unions and university was formed in 1988 to study the situation of industrial noise and hearing acuity of workers. Since 1982, the six industries identified by the Noise Control Office were construction, electronics, metals, plastics, shipbuilding and repairing, and textiles. Safety-subcommittees were formed. With the help of these subcommittees, 21 out of 32 medium-size factories responded to the study. A total of 922 sound measurements were made and 1062 out of 10724 workers were examined. More than one third (37.5%) of workers worked in locations with noise level in excess of L eq (8h) 90 dBA. Among examined subjects, 39.8% were exposed to L eq (8) 90 dBA and above and 18.6% were found to have industrial hearing loss. Multiple logistic regression analyses adjusted for sex and age showed that for hearing loss, the important risk factors were duration of occupational noise exposure, noise intensity, floor vibration and military experience. Current legislation and measures in hearing conservation were inadequate despite the implementation of inspection by the Noise Control Office. Recommendations were directed at amending relevant legislation, increasing supervision of use of personal ear protection, and strengthening health education and audiometric surveillance of exposed workers. PMID- 24233969 TI - Editorial. PMID- 24233968 TI - Analysis of pollution monitoring by expert systems. AB - Pollution monitoring can provide an important aid in the choice of the strategy to control the level of some dangerous elements, whether in water or in the air. The difficulties of detecting polluting sources from experimental data are related not only to the adoption of systematic and suitable measuring procedure, but also to a correct management of the available information. From the theoretical point of view, the use of simplified models, coupled with classical regularization techniques, shows that, in general, the problem is badly posed and consequently, numerically ill-conditioned. Hence the possibility of using expert systems algorithms, introducing further qualitative information, improves the reliability of the solutions. In particular, this paper deals with the utilization of fuzzy optimization algorithms: fuzzy theory supplies a formal reasoning technique, which proposes solutions that are real consequences of the premises.An actual example of such a method is described, making reference to the computation of the distribution of polluting sources from ground concentration data. The inverse problem is first solved using traditional procedures, showing that the distributed sources are not recognized. Afterwards, different results obtained from various algorithms derived from the assumed a-priori knowledge are examined. In this case, it is possible to obtain a more realistic situation of the pollution sources, inside the boundaries of the controlled area. PMID- 24233970 TI - Adherence to oral antivirals in patients with chronic hepatitis B infection. PMID- 24233971 TI - How statewide LGB policies go from ''under our skin'' to ''into our hearts'': fatherhood aspirations and psychological well-being among emerging adult sexual minority men. AB - Researchers have noted increasingly the public health importance of addressing discriminatory policies towards lesbian, gay, and bisexual (LGB) populations. At present, however, we know little about the mechanisms through which policies affect LGB populations' psychological well-being; in other words, how do policies get under our skin? Using data from a study of sexual minority young men (N = 1,487; M = 20.80 (SD = 1.93); 65% White; 92% gay), we examined whether statewide bans (e.g., same-sex marriage, adoption) moderated the relationship between fatherhood aspirations and psychological well-being. Fatherhood aspirations were associated with lower depressive symptoms and higher self-esteem scores among participants living in states without discriminatory policies. In states with marriage equality bans, fatherhood aspirations were associated with higher depressive symptoms and lower self-esteem scores, respectively. Fatherhood aspirations were associated negatively with self-esteem in states banning same sex and second parent adoptions, respectively. Our findings underscore the importance of recognizing how anti-equality LGB policies may influence the psychosocial development of sexual minority men. PMID- 24233972 TI - Expression of microRNAs is essential for arterial myogenic tone and pressure induced activation of the PI3-kinase/Akt pathway. AB - AIMS: The myogenic response is the intrinsic ability of small arteries to constrict in response to increased intraluminal pressure. Although microRNAs have been shown to play a role in vascular smooth muscle function, their importance in the regulation of the myogenic response is not known. In this study, we investigate the role of microRNAs in the regulation of myogenic tone by using smooth muscle-specific and tamoxifen-inducible deletion of the endonuclease Dicer in mice. METHODS AND RESULTS: In order to avoid effects of Dicer deletion on smooth muscle differentiation and growth, we used an early time point (5 weeks) after the tamoxifen-induction of Dicer knockout (KO). At this time point, we found that myogenic tone was completely absent in the mesenteric arteries of Dicer KO mice. This was associated with a reduced pressure-induced Akt phosphorylation, possibly via increased phosphatase and tensin homologue (PTEN) expression, which was found to be a target of miR-26a. Furthermore, loss of myogenic tone was associated with a decreased depolarization-induced calcium influx, and was restored by the L-type channel agonist Bay K 8644 or by transient stimulation with angiotensin II (Ang II). The effect of Ang II was dependent on AT1-receptors and activation of the PI3-kinase/Akt pathway. CONCLUSION: In this study we have identified novel mechanisms that regulate myogenic tone in resistance arteries, which involves microRNA-dependent control of PI3-kinase/Akt signalling and L-type calcium influx. Furthermore, we have demonstrated that transient stimulation by Ang II can have long-lasting effects by potentiating myogenic tone. PMID- 24233974 TI - Thermomagnetic surgery for cancer. AB - Thermomagnetic Surgery is a unique technique that takes advantage of the phenomenon of hysteresis heating of a ferromagnetic material to produce intense but controlled temperatures within solid organs or tumors to cause coagulation necrosis. By controlling the power of the electromagnetic coil system, the degree of heating of the tumor can be controlled through temperature monitoring that allows limitation of the area of destruction to the disease process and avoids damage to surrounding structures. If the ferromagnetic material is delivered by the arterial route to the tumor or organ, there is an additional beneficial effect of ischemic necrosis of the tissue and in time more concentration of the ferromagnetic particles. This new technique is applicable to selected cases of human cancer because no ill effect has been shown to exposure of the electromagnetic field or the ferromagnetic material in experimental animals. PMID- 24233975 TI - Rapid estimation of biochemical oxygen demand. AB - The feasibility of using columnar reactors containing immobilized microorganisms for the rapid estimation of BOD was demonstrated in this study. Dilutions of three types of industrial effluents were tested by the BOD5 test and by this experimental system. A high degree of correlation (r = 0.98) was observed between results of the two tests. The mean standard error of estimation of the experimental system was 11%. PMID- 24233973 TI - Avian influenza H5 hemagglutinin binds with high avidity to sialic acid on different O-linked core structures on mucin-type fusion proteins. AB - The interaction between P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL 1/mIgG(2b)) fusion protein carrying multiple copies of the influenza hemagglutinin receptor Siaalpha2-3Gal on different O-glycan chains and recombinant human influenza H5N1 A/Vietnam/1203/04 hemagglutinin was investigated with a Biacore biosensor. The fusion protein was produced by stable cell lines in large scale cultures and purified with affinity- and gel filtration chromatography. TheC-P55 and 293-P cell lines were established by transfecting the Chinese hamster ovary (CHO)-K1 and Human embryonic kidney (HEK)-293 cell lines with plasmids encoding the PSGL-1/mIgG(2b) fusion protein, while the C PSLex cell line was engineered by transfecting CHO-K1 cells with the plasmids encoding the core 2 beta1,6GnT-I and FUT-VII glycosyltransferases. Glycosylation was characterized by lectin Western blotting of the proteins and liquid chromatography - mass spectrometry of released non-derivatized O-glycans. Biacore experiments revealed that PSGL-1/mIgG(2b) is a good binding partner of H5. The binding curves displayed a slow dissociation indicating a multivalent binding. The H5 hemagglutinin binds with similar strength to PSGL-1/mIgG(2b) carrying mostly sialylated core 1 (clone C-P55), a mix of sialylated core 1 and sialylated lactosamine (clone 293-P) or mainly sialylated lactosamine (clone C-PSLex) O glycans, indicating that this hemagglutinin is unable to discriminate between these structures.The potential use of the large, flexible PSGL-1/mIgG(2b) mucin type fusion protein carrying Siaalpha2-3Gal as a multivalent inhibitor of influenza virus is discussed. PMID- 24233976 TI - Magnetic biospecific affinity adsorbents for immunoglobulin and enzyme isolation. AB - Magnetic biospecific affinity adsorbents for immunoglobulin and enzyme isolation have been prepared. They were obtained by a " post-magnetization" procedure involving a simple treatment of the various affinity gels with magnetic ferrofluid. The magnetic biospecific adsorbents tested include magnetic protein A Sepharose for isolation of IgG antibodies, magnetic human serum albumin (HSA) Sepharose for anti-HSA isolation, and magnetic 2',5'-ADP for isolation of glucose 6-phosphate dehydrogenase from baker's yeast and hemolyzates of human red blood cells. For the latter enzyme, a 11,000-fold purification was achieved in one step. PMID- 24233977 TI - Production of alpha-keto acids Part I. Immobilized cells ofTrigonopsis variabilis containing D-amino acid oxidase. AB - Whole cells ofTrigonopsis variabilis were immobilized by entrapment in Ca(2+) alginate and used for the production of alpha-keto acids from the corresponding D amino acids. The D-amino acid oxidase within the immobilized cells has a broad substrate specificity. Hydrogen peroxide formed in the enzymatic reaction was efficiently hydrolyzed by manganese oxide co-immobilized with the cells. The amino acid oxidase activity was assayed with a new method based on reversed-phase HPLC. Oxygen requirements, bead size, concentration of cells in the beads, flow rate, and other factors were investigated in a " trickle-bed " reactor. PMID- 24233978 TI - Analysis of a theoretical model for anisotropic enzyme membranes application to enzyme electrodes. AB - A theoretical model of diffusion and reaction in an anisotropic enzyme membrane is presented with particular emphasis on the application of such membranes in enzyme electrodes. The dynamic response of systems in which the kinetics are linear, which comprises the practical operating regime for enzyme electrodes in analysis, is investigated via an analytic solution of the governing differential equations. The response is presented as a function of a single dimensionless group, MU, that is the membrane modulus. PMID- 24233979 TI - Potentiometric and spectroscopic studies of the reaction between trypsin and its inhibitors on chemically modified solid surfaces. AB - The potential of a titanium metal electrode modified with trypsin changes as a result of the complex formation reaction between trypsin and its inhibitor, aprotinin, dissolved in the solution. A similar potential change in the opposite direction occurs by the reaction between aprotinin-modified electrode and trypsin in the solution. The induced changes in both cases depend on the pH of the solution, showing the maximum change at pH = 9.5. The potentiometric response of the trypsin-modified electrode for the consecutive addition of aprotinin and proflavine proves that trypsin bound on the solid surfaces reacts with aprotinin much more strongly than with proflavine. This result is fully consistent with the spectroscopically observed behavior of a trypsin-modified quartz plate against these inhibitors. The surface coverage of trypsin on the quartz plate is also determined by a near-ultraviolet absorption measurement. PMID- 24233980 TI - Recycling of NAD(+) using coimmobilized alcohol dehydrogenase andE. coli. AB - The use of immobilized enzymes has opened the possibility of large scale utilization of NAD(+)-linked dehydrogenases, but the applications of this technique were limited by the necessity of providing the large amounts of NAD(+) required by its stoichiometric consumption in the reaction. After immobilization of alcohol dehydrogenase and intactE. coli by glutaraldehyde in the presence of serum albumin, the respiratory chain was found to be capable of regenerating NAD(+) from NADH. This NAD(+) can be recycled at least 100 times, and thus the method is far more effective than any other, and, moreover, does not require NADH oxydase purification. The total NADH oxidase activity recovered was 10-30% of the initial activity.Although, NADH is unable to cross the cytoplasmic membrane, it was able to reach the active site of NADH dehydrogenase after immobilization. The best yield of NADH oxidase activity with immobilized bacteria was obtained without prior treatment of the bacteria to render them more permeable. The denaturation by heat of NADH oxidase in cells that are permeabilized was similar before and after immobilization. In contrast, the heat denaturation of soluble Beta-galactosidase required either a higher temperature or a longer exposure after immobilization. The sensitivity of immobilized NADH oxidase to denaturation by methanol was decreased compared to permeabilized cells. As a result, it is clear that the system can function in the presence of methanol, which is necessary as a solvent for certain water insoluble substrates. PMID- 24233981 TI - Patents and literature. PMID- 24233982 TI - Attention deficits: current concepts, controversies, management, and approaches to classroom instruction. AB - This article reviews the current criteria for diagnosis of Attention-Deficit Hyperactivity Disorder and Undifferentiated Attention-Deficit Disorder, according to the American Psychiatric Association, and describes other typical presenting features of children with attentional disorders. The current theories of the biological basis of attentional disorders are reviewed. Treatments of attentional disorders are discussed, including medical treatments with stimulants and tricyclic antidepressants, and non-medical treatments, such as behavior modification, psychotherapy, diets, and specific educational modifications that are felt to be helpful. Finally, our current thinking about the long-term outlook for children with attentional disorders is summarized. PMID- 24233983 TI - Occurrence and pattern of impaired reading and written language in children with attention deficit disorders. AB - The purpose of this study was to investigate the occurrence and severity of reading, spelling, and written language impairment in children clinically referred for Attention Deficit Hyperactivity Disorder (ADHD). Specific questions involved 1) whether ADD subgroups with and without hyperactivity differ in reading, spelling, and written language achievement, 2) whether age and gender interact with ADD sub-group class to affect reading/written language achievement, and 3) whether prevalence of impaired reading/written language in these subgroups is consistent with previous reports in heterogeneous samples. Subjects were 115 ADD children aged 6-12 who were subclassified as ADD + H(72 percent) and ADD - H(28 percent) by objective teacher ratings. Dependent measures included tests of single word recognition and vocabulary, word attack, contextual comprehension, written spelling, written sentence construction, and writing fluency, in addition to a structured behavioral observation, during which aspects of inattention and motor activity were coded. A large fraction of this sample met public school LD criteria (54 percent), and achievement on most measures was globally poorer than the respective test normative groups. The ADD + H subgroup showed significantly poorer word attack skills, while the subgroups did not significantly differ from each other on other reading/written language measures. However, 17 percent of the total ADD sample were >= 1.5 SD below the mean in total reading achievement, and 29 percent were >= 1.5 SD below the mean on measures of written spelling/language. Gender X age interactions, indicating poorer performance in the middle age group of females, were likely related to lower IQ. PMID- 24233984 TI - Familial dyslexia: genetic and medical findings in eleven three-generation families. AB - In addition to providing information on the inheritance of dyslexia, the present study of eleven three-generation families has provided a unique opportunity to compare affected and unaffected family members at all ages. The data presented here are based on pedigree information, a questionnaire administered to all participating family members in relation to sex ratio, handedness, the severity of dyslexia by sex, pre- and perinatal complications, medical complications, years of education and earning ability, and a battery of standardized tests to define the presence or absence of dyslexia. The pattern of inheritance was consistent with the postulated autosomal dominant mode of inheritance and penetrance was found to be > 90 percent. Of 73 individuals determined to have a gene leading to dyslexia, seven were classified as obligate carriers and six as compensated adults who had no current symptoms or diagnostic evidence of dyslexia. The sex ratio (1.06) was not different from the expected ratio of 1.04. Left-handedness, major pre- and perinatal complications, and autoimmune disorders and allergy were not more common in dyslexics than non-dyslexics. The number of years of education and average income were similar in affected and unaffected family members. Compensated adults and obligate carriers were similar to unaffected family members in each of these parameters. PMID- 24233985 TI - Sex differences in learning abilities and disabilities. AB - Boys more often than girls are affected by all the cognitive developmental disorders of childhood. Differences in the etiology of learning disabilities as well as general sex differences in learning styles in boys versus girls may explain the male preponderance in the prevalence of learning disabilities. The effects on learning of hormonal sex differences, maturation rate differences, and differences in frequency of perinatal brain injury will be discussed. PMID- 24233986 TI - Predicting reading performance using the slingerland procedures. AB - The purpose in this study was to examine predictive relationships between the Slingerland Pre- Reading Screening Procedures and performance on measures of word recognition and reading comprehension. Longitudinal data were collected on 104 children administered the Slingerland Procedures in kindergarten and the Stanford Achievement Test at first, third, and fifth grades. Outcome measures included achievement subtests, Word Study Skills, Reading Comprehension, Reading and Listening Total. Significant relationships were found between Slingerland measures and reading outcomes. However, prediction varied across grades and according to the measure of reading used. Listening contributed to reading comprehension but not to word recognition, and visual skills influenced early but not later reading performance. Gender and socioeconomic status influenced the strength of associations. PMID- 24233987 TI - Predicting reading progress in children receiving special help. AB - The main aim of the study was to determine whether performance on reading-related cognitive processing tasks would help predict reading progress in children receiving special help. The 86 subjects were initially aged six to eight years and most were followed up after two years. When variance due to IQ and age was accounted for, an orthographic processing task, phonological awareness (phoneme deletion), and digit- naming speed were significant predictors of later reading skills. A strength in phonological awareness differentiated initial poor readers who later made excellent gains in reading from poor readers who did not improve. Children whose reading deteriorated had serious weaknesses on tasks of naming speed and confrontation naming. Their poor lexical retrieval skills had a more deleterious effect on later reading than on initial. Indications were that for children diagnosed as poor readers at age six or seven years, prognosis is better for boys, and for garden- variety poor readers, than for dyslexics. Caution was urged in applying the term dyslexic to children in the first two school grades because many of them will be slow starters who do not have a persistent reading problem. PMID- 24233988 TI - Is there a visual dyslexia. AB - Traditionally, it has been speculated that weaknesses in the visual processing of cognitive aspects of the written word could lead to reading problems, and if so, such a condition would constitute a subtype of developmental dyslexia. This putative subtype has been referred to as visual dyslexia. In this article, the role of cognitive deficits that are visual in nature as a potential etiological factor of developmental dyslexia is examined. Following a brief history of the study of dyslexia, a critique of studies of visual dyslexia is presented. Subsequently, the nature of the visual processes involved in word- recognition is examined. Finally, three research studies that assessed the contribution of visual memory to word-recognition are presented. It is concluded that, even though defects in the physiological aspects of visual processing can lead to reading difficulties, at present little convincing evidence is available to conclude that a subtype of dyslexia caused by cognitive deficits associated with visual processing of information exists. PMID- 24233989 TI - On the interaction between phonological awareness and reading acquisition: It's a two-way Street. AB - We have investigated the reciprocal influence of reading acquisition and phonemic awareness. Using a between-grades quasi-experimental design, we have found that learning to read is the most important factor that accounts for the drastic improvement of phonemic segmentation skills during the first year of schooling. On the other hand, we found that improving phonemic skills in kindergarten facilitated reading acquisition in children at risk for developing reading disorders. We suggest that, for most children, exposure to the alphabet automatically triggers phonemic awareness, which is a necessary condition for efficient acquisition of reading. However, the emergence of phonemic awareness requires a previously developed sensitivity to phonology, which in some children may be absent. The present data suggest that, if phonological skills are absent, they may be developed in preschoolers by explicit training, thereby preventing failure in reading acquisition. PMID- 24233990 TI - Phoneme awareness in language-delayed children: comparative studies and intervention. AB - Our initial study compared 15 normally- developing and 13 language- delayed four- and- five- year- olds on a range of phoneme awareness tasks differing in the degree of explicit linguistic analysis required. The language- delayed group performed more poorly than the normally- developing children, and there were significant group differences on several tasks. A significant interaction effect reflected the particular difficulty the language- delayed group had with the more explicit tasks. Follow- up testing suggests that group differences are maintained over time and that the language- delayed children perform more poorly than the normally- developing children on tests of decoding and spelling at the end of first grade.An intervention study, training phoneme awareness skills in language delayed kindergarten children, was undertaken with a new group of subjects. Fourteen language- delayed children participated in 16 training sessions over eight weeks. Fourteen normal and 14 language- delayed children served as controls. Only the language- delayed training group made significant gains from pre- to posttraining measures. Following training, the language-delayed training group performed similarly to normal controls and significantly better than language- delayed controls whom they had matched before intervention. One year later, the language-delayed children who received training maintained their gains on phoneme analysis tasks and performed significantly better than the language delayed controls on reading measures. Educational implications are discussed. PMID- 24233991 TI - Spelling error interpretation: beyond the phonetic/dysphonetic dichotomy. AB - If spelling errors are classified simply as auditory or visual, or as phonetically accurate or inaccurate, manifestations of both developmental phenomena and possible linguistic process deficits in spelling may be overlooked or misinterpreted. Phonological process deficits in spelling are more complex than simple phonetic ratings will reflect. Spelling errors may yield useful information about specific language disabilities if linguistically informed criteria for analysis are employed. PMID- 24233992 TI - Spelling improvement for college students who are dyslexic. AB - Academic problems of the dyslexic child often persist in adult life. Such problems as spelling can interfere with the performance of such adult learners in college. Federal legislation requires reasonable accommodation for these students. At some colleges, this consists of allowing use of tape recorders in lectures and sometimes allowing extra time on examinations. Remediation of reading, writing, and spelling among dyslexic college students is often not addressed. This study reports the use of a modified Orton-Gillingham approach in comparison with a nonphonetic approach and with a group receiving no remediation. The results indicate a significant increase in spelling performance for the group receiving the modified Orton-Gillingham remediation. This contrasts with no significant change in the group receiving nonphonetic remediation and in the control group (no remediation), and indicates that adulthood is not too late for appropriate intervention for the dyslexic student. Colleges offering such intervention and the students receiving it will benefit from improved performance. PMID- 24233993 TI - The effects of multisensory structured language instruction on native language and foreign language aptitude skills of at-risk high school foreign language learners: A replication and follow-up study. AB - According to research findings, most students who experience foreign language learning problems are thought to have overt or subtle native language learning difficulties, primarily with phonological processing. A recent study by the authors showed that when a multisensory structured language approach to teaching Spanish was used with a group of at-risk high school students, the group's pre- and posttest scores on native language phonological processing, verbal memory and vocabulary, and foreign language aptitude measures significantly improved. In this replication and follow-up study, the authors compared pre- and posttest scores of a second group of students (Cohort 2) who received MSL instruction in Spanish on native language and foreign language aptitude measures. They also followed students from the first study (Cohort 1) over a second year of foreign language instruction. Findings showed that the second cohort made significant gains on three native language phonological measures and a test of foreign language aptitude. Follow-up testing on the first cohort showed that the group maintained its initial gains on all native language and foreign language aptitude measures. Implications for the authors' Linguistic Coding Deficit Hypothesis are discussed and linked with current reading research, in particular the concepts of the assumption of specificity and modularity. PMID- 24233994 TI - Monitoring learning-disabled students in mainstream science classes. AB - While science classes are believed to be interactive learning environments, offering varied ways for students to learn, some experts believe that learning disabled (LD) students should be monitored closely in such settings because of difficulties adjusting to the social, behavioral, and academic demands. The purpose of this paper is to determine whether LD fourth and sixth graders show difficulties adjusting to the demands of their mainstream science classes and to investigate two means of assessing LD students' functioning in these classes: paired questionnaires for teachers and students and a science curriculum-based assessment (CBA). Subjects include 31 fourth graders (9 LD) and 38 sixth graders (13 LD). Results show that the LD students had significant weaknesses on some subtests of the science CBA relative to their peers; additionally, they rated themselves and were rated by their teachers significantly more negatively than their Non-LD peers. These results suggest the potential value of monitoring LD students in mainstream science classes. Case studies of LD students reveal mismatches in the perception of the student and teacher regarding the student's adjustment and classroom habits. Examination of these case studies is used to suggest ways in which the collaboration of student and teacher as well as regular and special education teachers might aid the student. PMID- 24233995 TI - Using computer-based readers to improve reading comprehension of students with dyslexia. AB - Twenty-eight middle school students, diagnosed as dyslexic and attending a school using the Slingerland approach to remediation of dyslexia, used a computer-based reading system for reading literature for about one-half hour a day for a semester. The system proved to be a strong compensatory aid, enabling 70 percent of the students to read with greater comprehension, approximately one grade level or more improvement, as measured by the Gray Oral Reading Test. For 40 percent of the students, the gains were large, from two to as much as five grade levels. However, not all students benefited. Fourteen percent showed lower comprehension scores when using the system, and there is some indication that this degradation is associated with kinesthetic-motor weakness. Some students reported gains in reading speed and exhibited increased span of attention for and endurance in reading when using the system. We did not find evidence that the computer-reader technology provided a positive remediation benefit incremental to that obtained from the school's intensive Slingerland remediation program. Our results indicate that computer-readers are important compensatory aids that can enable many people with dyslexia to perform more effectively in reading-related tasks associated with school and work. PMID- 24233996 TI - Project ASSIST institute: An orton-gillingham/spalding based curriculum for teachers and volunteers. AB - In spite of our best efforts, our son Andrew did not learn to read until he attended the Jemicy School at the age of 12. Our search for help and eventual success led me to take the Orton-Gillingham approach into the public schools of Delaware, first with volunteers and then with teachers.In 1991-92, the Milford School District did a Pre-Post Design pilot using the Woodcock Johnson Reading Mastery Test for decoding and comprehension and the WRAT Revised for spelling. The results are included.Another pilot with a control group from another school district is being done in 1992-93 and a third pilot is being planned for New Castle County, Delaware in 1993-94.Training for teachers in the juvenile justice system is also planned for 1993-94. PMID- 24233997 TI - Dyslexia in the workplace: Implications of the Americans with disabilities act. AB - The Americans with Disabilities Act of 1990 (ADA) insures greater accessibility of disabled persons to the workplace. This includes persons with dyslexia and other learning disabilities. The ADA requires reasonable accommodations for persons with disabilities, yet it is different in its mandates from many other federal laws addressing disability-related issues.This article reviews some of the critical provisions of the ADA as it applies to persons with dyslexia, outlines a procedure through which the employer and employee negotiate accommodations, and offers examples of typical workplace problems and corresponding modifications. Finally, some of the talents and strengths often associated with dyslexia are described, as is their potential value in the workplace. PMID- 24233998 TI - Foreword. PMID- 24233999 TI - Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. AB - Tamoxifen is known to reduce the risk of breast cancer in women at high risk and also reduces mammographic breast density (MD) in a preventive setting. We investigated the efficacy of MD reduction (MDR) for predicting recurrence in estrogen receptor (ER)-positive patients in an adjuvant setting. A total of 1,066 ER-positive breast cancer patients who were enrolled in this study underwent curative surgery and received adjuvant tamoxifen for at least 2 years at our institution between January 2003 and December 2008. Using a computerized system, a single radiologist reviewed all mammograms and classified MD patterns on the basis of the Breast Imaging Reporting and Data System. MDR was assessed using the baseline mammogram taken before surgery (preMD) and the followup mammogram taken after the start of adjuvant tamoxifen(postMD). MDR positivity was defined as downgrading of the postMD grade, with the preMD grade as a reference.Patients were divided into 2 groups, MDR-positive and MDR-negative, for statistical analysis. Patients who showed MDR after an average of 19 months of adjuvant tamoxifen treatment had a 65 % lower risk of recurrence than patients who did not show MDR. Furthermore, significant risk reduction according to MDR had a predictive power for any type of recurrence pattern including loco-regional recurrence(87 % reduction) and systemic recurrence (52 %reduction) in ER-positive breast cancer patients, especially in women <=50 years. In our study, only 4 patients (0.4 %)showed contralateral breast recurrence during the mean 61-month follow-up period and none of them experienced MDR. In conclusion, MDR during adjuvant tamoxifen therapy was independently associated with a lower risk of systemic and loco-regional recurrence in ER-positive breast cancer patients, especially in young women. For patients who do not experience MDR after approximately 1.5 years of tamoxifen therapy, more caution should be taken and other treatment strategies are warranted. PMID- 24234001 TI - Fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: better 5-year survival or artifactual result of research methodology? PMID- 24234002 TI - ClockstaR: choosing the number of relaxed-clock models in molecular phylogenetic analysis. AB - SUMMARY: Relaxed molecular clocks allow the phylogenetic estimation of evolutionary timescales even when substitution rates vary among branches. In analyses of large multigene datasets, it is often appropriate to use multiple relaxed-clock models to accommodate differing patterns of rate variation among genes. We present ClockstaR, a method for selecting the number of relaxed clocks for multigene datasets. AVAILABILITY: ClockstaR is freely available for download at http://sydney.edu.au/science/biology/meep/software/. PMID- 24234003 TI - footprintDB: a database of transcription factors with annotated cis elements and binding interfaces. AB - MOTIVATION: Traditional and high-throughput techniques for determining transcription factor (TF) binding specificities are generating large volumes of data of uneven quality, which are scattered across individual databases. RESULTS: FootprintDB integrates some of the most comprehensive freely available libraries of curated DNA binding sites and systematically annotates the binding interfaces of the corresponding TFs. The first release contains 2422 unique TF sequences, 10 112 DNA binding sites and 3662 DNA motifs. A survey of the included data sources, organisms and TF families was performed together with proprietary database TRANSFAC, finding that footprintDB has a similar coverage of multicellular organisms, while also containing bacterial regulatory data. A search engine has been designed that drives the prediction of DNA motifs for input TFs, or conversely of TF sequences that might recognize input regulatory sequences, by comparison with database entries. Such predictions can also be extended to a single proteome chosen by the user, and results are ranked in terms of interface similarity. Benchmark experiments with bacterial, plant and human data were performed to measure the predictive power of footprintDB searches, which were able to correctly recover 10, 55 and 90% of the tested sequences, respectively. Correctly predicted TFs had a higher interface similarity than the average, confirming its diagnostic value. AVAILABILITY AND IMPLEMENTATION: Web site implemented in PHP,Perl, MySQL and Apache. Freely available from http://floresta.eead.csic.es/footprintdb. PMID- 24234004 TI - ISCB: past-present perspective for the International Society for Computational Biology. AB - Since its establishment in 1997, International Society for Computational Biology (ISCB) has contributed importantly toward advancing the understanding of living systems through computation. The ISCB represents nearly 3000 members working in >70 countries. It has doubled the number of members since 2007. At the same time, the number of meetings organized by the ISCB has increased from two in 2007 to eight in 2013, and the society has cemented many lasting alliances with regional societies and specialist groups. ISCB is ready to grow into a challenging and promising future. The progress over the past 7 years has resulted from the vision, and possibly more importantly, the passion and hard working dedication of many individuals. PMID- 24234005 TI - SeqDepot: streamlined database of biological sequences and precomputed features. AB - Assembling and/or producing integrated knowledge of sequence features continues to be an onerous and redundant task despite a large number of existing resources. We have developed SeqDepot-a novel database that focuses solely on two primary goals: (i) assimilating known primary sequences with predicted feature data and (ii) providing the most simple and straightforward means to procure and readily use this information. Access to >28.5 million sequences and 300 million features is provided through a well-documented and flexible RESTful interface that supports fetching specific data subsets, bulk queries, visualization and searching by MD5 digests or external database identifiers. We have also developed an HTML5/JavaScript web application exemplifying how to interact with SeqDepot and Perl/Python scripts for use with local processing pipelines. AVAILABILITY: Freely available on the web at http://seqdepot.net/. RESTaccess via http://seqdepot.net/api/v1. Database files and scripts maybe downloaded from http://seqdepot.net/download. PMID- 24234006 TI - Quality assurance in the clinical genetics setting-Report of a workshop. AB - Participants in a panel discussion sponsored by thead hoc Quality Assurance Committee of the National Society of Genetic Counselors discuss early efforts to develop and implement quality assurance instruments at institutional, state, and regional levels. Uniform guidelines and self-assessment tools can help genetic counselors and clinical geneticists to provide the best possible care to individuals affected by genetic diseases. Further work will be needed to address aspects not covered here and to assure that guidelines allow for creative variation among professionals and centers. An interdisciplinary approach to such standard-setting is recommended. PMID- 24234007 TI - Suicide prevention in the genetic counseling context. AB - Utilizing a case report, this paper explores psychosocial aspects of suicidal intent in a woman seeking prenatal diagnosis. Using knowledge and practice of appropriate assessment, referral, and intervention procedures, the therapy team of genetic counselor and psychotherapist facilitated successful identification and management of this potentially suicidal client. The main counseling goals for the genetic counselor are to assess the situation adequately, decrease the immediate danger, and, with supervision and/or consultation, stabilize the seriously suicidal person until that individual can be triaged to mental health or medical professionals for treatment. The prevalence of suicide issues in genetic counseling contexts is unknown and reports mentioning suicidal ideation unusual in the genetic counseling literature. Is this reported case a rarity among genetic counseling referrals? Systematically collected information on the prevalence and resolution of suicidal issues in genetic counseling contexts would be helpful for those setting curricula for genetic counseling training programs, standards for professional certification exams, and policy and procedures manuals for clinical units. PMID- 24234008 TI - Practice variability in prenatal genetic counseling. AB - This study demonstrated that the content of prenatal genetic counseling sessions varied from counselor to counselor and from center to center. The study was designed to examine which specific issues were included by genetic counselors in prenatal genetic counseling sessions, and to determine which factors led genetic counselors to include or exclude this information from such sessions. Data were collected by randomly surveying 200 full, master degree members of the National Society of Genetic Counselors (NSGC). Respondents provided information by deciding which of 45 specific issues they would include in a standard prenatal genetic counseling session, and which one factor from a bank of 11 factors most accurately described the reason for this decision. The results indicated that the issues included/excluded from sessions varied widely among genetic counselors. The results also indicated that Patient Education/Informed Decision Making (34.5%) played the largest role in decision making overall, with Standard at Center/Departmental Policy (17.6%), Personal Experience/Preference (12.4%), and Applicability (10.9%) serving as the next three most important reasons for including or excluding issues from prenatal genetic counseling sessions. PMID- 24234009 TI - Molecular carrier testing for the fragile X syndrome: Issues for genetic counselors. AB - Molecular analysis of the fragile X (FMR-1) gene identifies female fragile X carriers, but appropriate genetic counseling can only be provided if the limitations of the testing methods are understood. Molecular analysis of this gene is achieved with both the polymerase chain reaction (PCR) and Southern blot techniques. PCR is faster and can determine the actual number of CGG repeats, which modifies genetic counseling substantially. However, for a sizeable percentage of women, PCR alone is not conclusive, and Southern analysis is necessary to complete the study. While this procedure takes longer, it is usually conclusive. Women who present for genetic counseling and carrier testing in the second trimester of pregnancy need this information quickly, and for them the turn-around time is paramount. It is critical that genetic counselors understand these methods so that they can educate their clients and facilitate appropriate follow-up. PMID- 24234010 TI - Protein composition of endurance trained human skeletal muscle. AB - Evidence suggests that myofibers from endurance trained skeletal muscle display unique contractile parameters. However, the underlying mechanisms remain unclear. To further elucidate the influence of endurance training on myofiber contractile function, we examined factors that may impact myofilament interactions (i. e., water content, concentration of specific protein fractions, actin and myosin content) or directly modulate myosin heavy chain (MHC) function (i. e., myosin light chain (MLC) composition) in muscle biopsy samples from highly-trained competitive (RUN) and recreational (REC) runners. Muscle water content was lower (P<0.05) in RUN (73+/-1%) compared to REC (75+/-1%) and total muscle and myofibrillar protein concentration was higher (P<0.05) in RUN, which may indicate differences in myofilament spacing. Content of the primary contractile proteins, myosin (0.99+/-0.08 and 1.01+/-0.07 AU) and actin (1.33+/-0.09 and 1.27+/-0.09 AU) in addition to the myosin to actin ratio (0.75+/-0.04 and 0.80+/-0.06 AU) was not different between REC and RUN, respectively, when expressed relative to the amount of myofibrillar protein. At the single-fiber level, slow-twitch MHC I myofibers from RUN contained less (P<0.05) MLC 1 and greater (P<0.05) amounts of MLC 3 than REC, while MLC composition was similar in fast-twitch MHC IIa myofibers between REC and RUN. These data suggest that the distinctive myofiber contractile profile in highly-trained runners may be partially explained by differences in the content of the primary contractile proteins and provides unique insight into the modulation of contractile function with extreme loading patterns. PMID- 24234011 TI - Chronic eccentric cycling improves quadriceps muscle structure and maximum cycling power. AB - An interesting finding from eccentric exercise training interventions is the presence of muscle hypertrophy without changes in maximum concentric strength and/or power. The lack of improvements in concentric strength and/or power could be due to long lasting suppressive effects on muscle force production following eccentric training. Thus, improvements in concentric strength and/or power might not be detected until muscle tissue has recovered (e. g., several weeks post training). We evaluated alterations in muscular structure (rectus-femoris, RF, and vastus lateralis, VL, thickness and pennation angles) and maximum concentric cycling power (Pmax) 1-week following 8-weeks of eccentric cycling training (2*/week; 5-10.5 min; 20-55% of Pmax). Pmax was assessed again at 8-weeks post training. At 1 week post-training, RF and VL thickness increased by 24+/-4% and 13+/-2%, respectively, and RF and VL pennation angles increased by 31+/-4% and 13+/-1%, respectively (all P<0.05). Compared to pre-training values, Pmax increased by 5+/-1% and 9+/-2% at 1 and 8 weeks post-training, respectively (both P<0.05). These results demonstrate that short-duration high-intensity eccentric cycling can be a time-effective intervention for improving muscular structure and function in the lower body of healthy individuals. The larger Pmax increase detected at 8-weeks post-training implies that sufficient recovery might be necessary to fully detect changes in muscular power after eccentric cycling training. PMID- 24234012 TI - Total haemoglobin mass, maximal and submaximal power in elite rowers. AB - Elite rowers are highly endurance trained and present with a large lean body mass (LBM), which is closely related to total haemoglobin mass (tHbmass), a major determinant of blood O2-transport. This study aims to determine the magnitude of tHbmass in elite rowers and its relation to performance parameters that are common in rowing worldwide. 13 rowers (3 lightweight) performed a 2000 m test to evaluate maximal performance on the rowing ergometer (P2k) and an incremental test to evaluate power output at lactate 2 and 4 mmol/l (N=15). tHbmass was measured by CO-rebreathing. tHbmass amounted to 1285+/-123 g (open weight) and 1059+/-48 g (lightweight). Coefficients of correlation between tHbmass and power output increased with intensity, being highest for P2k (r=0.80). An increase of 100 g tHbmass is associated with an increase of 24 W in P2k between subjects. The ratio between tHbmass/LBM amounted to approximately 16 g/kg. Absolute tHbmass in elite rowers of open weight class is very high. In relation to body mass or LBM, data is similar to other endurance athletes. The relation between P2k performance and tHbmass is very large. However, it is partly mediated by body composition. PMID- 24234013 TI - Phytotoxic and antimicrobial activity of 5,7-dihydroxychromone from peanut shells. AB - A flavonoid decomposition product that is present in peanut (Arachis hypogaea) shells, 5,7-dihydroxychromone (DHC), was found to inhibit the radial growth of cultures of the soil pathogenic fungiRhizoctonia solani andSclerotium rolfsii with I50 (the concentrations of DHC required to inhibit growth 50%) values of 18 and 26uM, respectively. Radicle elongation of velvetleaf, corn, peanut, and wheat was inhibited by DHC with I50 values of 30, 50, 65 and 200uM, respectively. DHC had no effect on the growth ofBradyrhizobium sp. at 10uM in medium containing low (1.0 g/liter) mannitol as the carbon source, although the related flavones luteolin and chrysin each promoted bacterial growth at 10uM 48 hr after inoculation. When tested in high (10.0 g/liter) mannitol medium, DHC initially inhibited growth ofBradyrhizobium sp., but 120 hr after inoculation the growth of all treatments were similar. These results suggest a role for DHC released from peanut shells in suppressing pathogenic fungal infection and competing plant growth but not forBradyrhizobium growth promotion. PMID- 24234014 TI - Extraction of phenolic compounds from fresh leaves: A comparison of methods. AB - The conventional sonicator/shaker bath method for phenolic extraction was compared with a less traditional one using a homogenizer. The homogenizer proved to be both more efficient and consistent in extracting phenolics from tender, as well as tough, leaves. We propose that adoption of the homogenizer technique will increase phenolic yield and efficiency. PMID- 24234015 TI - Dried leaves from rocky mountain plants decrease infestation by stored-product beetles. AB - Leaves of two highly aromatic plants,Artemisia tridentata (Nutt.) andMonarda fistulosa L., prepared according to a patented process, inhibited oviposition by the Mexican bean weevil,Zabrotes subfasciatus (Boheman), in beans at concentrations less than 1% w/w. Both plant species were less effective against the rice weevil,Sitophilus oryzae L., in wheat, with onlyM. fistulosa exhibiting any concentration-dependent activity. The maximal control achieved against this species was less than 50% at 3% w/w. Two less aromatic plant species,Balsamorhiza sagittata (Pursh.) Nutt. andGeranium viscosissimum Fisch. and Mey., caused only low levels of inhibition against both insect species. Volatiles probably caused the response toA. tridentata andM. fistulosa, while the asymptotic concentration dependence for the less volatile plant material was likely caused by behavioral factors related to the physical presence of foreign particulate matter in the foodstuff. Chemical analysis indicated that most of the volatile components from the dried leaf material from all species were terpenoids, with camphor (9.7 mg/g) and 1,8-cineole (4.0 mg/g) being most abundant inA. tridentata and carvacrol (26.3 mg/g) being most abundant inM. fistulosa. PMID- 24234016 TI - Pheromones in white pine cone beetle,Conophthorus coniperda (schwarz) (Coleoptera: Scolytidae). AB - Female white pine cone beetles,Conophthorus coniperda, attacking second-year cones of eastern white pine,Pinus strobus L., produced a sex-specific pheromone that attracted conspecific males in laboratory bioassays and to field traps. Beetle response was enhanced by host monoterpenes. The female-produced compound was identified in volatiles collected on Porapak Q and in hindgut extracts as (+) trans-pityol, (2R,5S)-(+)-2-(1-hydroxy-1-methylethyl)-5-methyltetrahydrofuran. Males and females produced and released the (E)-(-)-spiroacetal, (5S,7S)-(-)-7 methyl-1,6-dioxaspiro[4.5]decane, which was not an attractant for either sex, but acted as a repellent for males. Porapak Q-trapped volatiles from both sexes contained (+)-trans-pinocarveol and (-)-myrtenol. In addition, hindgut extracts of females containedtrans-verbenol, while males had pinocarvone and verbenone. Work in Georgia and Canada confirmed that the same isomers of pityol and spiroacetal are present in two distinct and widely separated populations ofC. coniperda. PMID- 24234017 TI - Pheromones in red pine cone beetle,Conophthorus resinosae hopkins, and its synonym,C. banksianae McPherson (Coleoptera: Scolytidae). AB - Analyses of abdominal extracts and beetle-produced volatiles revealed that femaleConophthorus resinosae andC. banksianae produced optically pure (E)-(+) pityol [(2R,5S)-(+)-2-(1-hydroxy-1-methylethyl)-5-methyltetrahydrofuran]. In field tests, traps baited with (E)-(+/-)- or (E)-(+)-pityol captured only males. Addition of host oils to traps baited with pityol did not significantly enhance the capture of males. Males of these former sibling species produced the spiroacetal (5S,7S)-(-)-7-methyl-1,6-dioxaspiro[4.5]decane with high optical purity (96%). Addition of the racemate or the optical isomers of the spiroacetal to traps baited with (E)-(+/-)-pityol almost completely inhibited the capture of males. It is hypothesized that to ensure their reproductive success, males produce the spiroacetal to repel rival males. Species specificity in pityol and the spiroacetal was not found betweenC. resinosae andC. banksianae, thus supporting their synonymy. PMID- 24234018 TI - Ethylene emission by a deciduous tree,Tilia americana, in response to feeding by introduced basswood thrips,Thrips calcaratus. AB - Ethylene emission from excised and intact American basswood tissue was increased after seedlings were infested with the bud-feeding herbivore,Thrips calcaratus. Gas chromatographic analysis showed that thrips-infested tissue produced significantly more ethylene than mechanically damaged or control tissue. The possibility that thrips feeding enhances ethylene-mediated stress signals is discussed. PMID- 24234019 TI - Determining enantiomeric composition of disparlure. AB - A method has been developed to convert disparlure (2-methyl-7,8-epoxyoctadecane) to the correspondingN-(alpha-methylbenzyl)aziridine with inversion of configuration at both the 7 and 8 positions. The diastereomeric aziridines can be separated on an efficient gas chromatography column, permitting determination of the enantiomeric constitution of the starting disparlure. As little as ca. 0.1% of the minor enantiomer can be detected. PMID- 24234020 TI - Volatile components in scent gland secretions of garter snakes (Thamnophis spp.). AB - Previous analyses of the scent gland secretions of snakes have focused on the nonvolatile components. Gas chromatography-mass spectrometry of secretions from North American garter snakes (Thamnophis butleri, T. couchi, T. elegans, T. melanogaster, andT. sirtalis) indicated the following seven major volatile components: acetic, propanoic, 2-methylpropanoic, butanoic, and 3-methylbutanoic acids, trimethylamine, and 2-piperidone. Five or more of these compounds were observed in secretions of select boid, colubrid, pythonid, and viperid snakes, suggesting that they are widespread scent gland products. 3-Methylbutanal also was detected in some snake species. PMID- 24234021 TI - Biorationals fromNicotiana protect cucumbers againstColletotrichum lagenarium (Pass.) ell. & halst disease development. AB - Trichome exudate compounds isolated from leaves ofNicotiana tabacum, N. glutinosa (accessions 24 and 24a), and 21 otherNicotiana species were evaluated for biorational activity againstC. lagenarium, the anthracnose pathogen of cucumber. Exudate compounds tested were the cembrane diterpenes alpha- and beta-4,8,13 duvatriene-1,3-diols (DVT diols); the labdane diterpenes (13-E)-labda-13-ene 8alpha,15-diol (labdenediol) and (13-R)-labda-14-ene-8alpha, 13-diol (sclareol); extracts fromN. gossei; and various sugar ester isolates. In dose-response experiments test compounds were applied to a water agar surface that was then inoculated with a conidial suspension. Low levels of most test compounds reduced or completely inhibited germination ofC. lagenarium conidia. IC50 values, concentrations (micrograms per square centimeter) at which conidium germination was reduced 50%, were 6.3 for DVT diols, 19.3 for sclareol, 1.0 for labdenediol, 2.8 for a mixture of sclareol and labdenediol, 1.2 for anN. gossei sucrose ester and 4.1 for theN. gossei crude extract. Higher levels of DVT diols and the sclareol-labdenediol mixture were required to reduce lesion size and number on inoculated cucumber leaves. At the highest concentration tested, 100 ug/cm(2), the DVT diols and sclareol-labdenediol mixtures protected cucumbers against lesion development by 93 and 98%, respectively. Sugar ester mixtures from 20Nicotiana species and three different sugar ester fractions fromN. bideglovii had in vitro antifungal activity at a concentration of 48 ug/cm(2). Sugar esters from nine of the species includingN. acuminata, N. attenuata, N. clevelandii, N. maritima, N. miersii, N. noctiflora, N. occidentalis, N. rustica, and fractions 10, 12, and 13 fromN. bideglovii completely inhibitedC. lagenarium conidium from germinating. Sugar ester mixtures from only four species,N. plumbaginifolia, N. bonariensis, N. simulans, andN. palmerii, had no significant effect onC. lagenarium conidium germination. These results suggest the potential ofNicotiana exudates as biorationals in reducing disease development. PMID- 24234022 TI - Sequestration of lichen compounds by three species of terrestrial snails. AB - Three species of lichen-grazing snails,Balea perversa, Chondria clienta, andHelicigona lapicida, all from the Swedish island of Oland, were found to sequester lichen compounds when feeding on the crustous lichen speciesAspicila calcarea, Caloplaca flavovirescens, Lecanora muralis, Physcia adscendens, Tephromela atra, andXanthoria parietina. The lichen compounds detected in the soft bodies of the snail species analyzed included the anthraquinone parietin, the depside atranorin, as well as a presumable degradation product of the latter. Other lichen compounds such as (+)-usnic acid or alpha-collatolic acid were not found in the soft bodies but were only detected in the feces, suggesting selective uptake of lichen compounds by the snails. In individuals ofC. clienta initially fed on the lichenX. parietina, the amount of sequestered parietin decreased over time on a parietin-free diet but was still detectable in the soft bodies after 28 days. In the ovoviviparous land snail,B. perversa, sequestered parietin was transferred from the mother to the eggs in the reproductive tract. PMID- 24234023 TI - Morphology and chemistry of brown rat,Rattus norvegicus, preputial and clitoral glands. AB - In contrast to previous results from laboratory rats, when sexual dimorphism occurred, clitoral glands from wild female rats were heavier and accounted for a greater proportion of body mass than preputial glands from wild males. Gland length and weight increased with body weight, but gland weight as a proportion of body weight did not. Preputial and clitoral glands showed seasonal differences in size: at one site glands were smaller in December than in April. Maturity, estrus, and pregnancy had no significant effect on clitoral gland size, but immature males had proportionally smaller preputial glands than mature males, and the absolute gland weight, but not gland weight as a proportion of body weight, increased with testes weight. There were no differences between the sexes in lipid production, which increased with preputial or clitoral gland weight. An homologous series of aliphatic acids and their methyl and ethyl esters, plus squalene, cholesterol and lanosterol, was revealed by GC-MS study of the trimethyl silyl derivatized lipid extract. Males and females could be distinguished by principal component analysis of chromatogram peaks. PMID- 24234025 TI - Atmospheric dispersion of radon gas and its decay products under stable conditions in arid regions of Australia. AB - The radon and radon daughter concentration-in-air from natural background are assessed along with the micrometeorology and synoptic weather systems in an arid region of Australia. The radon daughter contribution to population dose is biased towards the frequency of nocturnal inversions. Classical atmospheric models are not applicable during stable atmospheric conditions in inland Australia. An atmospheric Box Model is used along with measured data from tethersonde profiles in predicting radon/radon daughter concentration-in-air. Predicted and measured concentrations are compared for spatial and temporal variations. PMID- 24234026 TI - A comparative study on hospital sewage and industrial waste water. PMID- 24234027 TI - A selection of forest condition indicators for monitoring. AB - Regional monitoring and assessments of the health of forested ecosystems require indicators of forest conditions and environmental stresses. Indicator selections depend on objectives and the strategy for data collection and analysis. This paper recommends a set of indicators to signal changes in forest ecosystem distribution, productivity, and disturbance. Additional measurements are recommended to help ascribe those changes to climate variation, atmospheric deposition, and land use patterns. The rationale for these indicators is discussed in the context of a sequential monitoring and assessment strategy. PMID- 24234028 TI - Methods used for estimating fugitive emission rates of air pollutants and their application in China. AB - This paper presents a series of methods for measuring and estimating fugitive emission rates, which have been widely applied in environmental impact assessment and establishing national emission standard and health protection zone (buffer zone) standards in China. PMID- 24234029 TI - Organochlorines and heavy metals in 17-year cicadas pose no apparent dietary threat to birds. AB - Organochlorine and heavy metal concentrations in 17-year cicadas from Prince Georges and Anne Arundel Counties, Maryland, were well below levels known to be harmful to birds. Cicadas contained concentrations of metals similar to or less than other local invertebrates except they contained more copper than did earthworms. Copper and lead concentrations in cicadas from one site may have been elevated by sewage plant effluent deposited during river floodings. Cicadas from the median of a major highway did not contain more lead than cicadas from non traffic sites. PMID- 24234030 TI - Sampling and analysis for radon-222 dissolved in ground water and surface water. AB - Radon-222 is a naturally occurring radioactive gas in the uranium-238 decay series that has traditionally been called, simply, radon. The lung cancer risks associated with the inhalation of radon decay products have been well documented by epidemiological studies on populations of uranium miners.The realization that radon is a public health hazard has raised the need for sampling and analytical guidelines for field personnel. Several sampling and analytical methods are being used to document radon concentrations in ground water and surface water worldwide but no convenient, single set of guidelines is available. Three different sampling and analytical methods-bubbler, liquid scintillation, and field screening-are discussed in this paper. The bubbler and liquid scintillation methods have high accuracy and precision, and small analytical method detection limits of 0.2 and 10 pCi/l (picocuries per liter), respectively. The field screening method generally is used as a qualitative reconnaissance tool. PMID- 24234031 TI - Comparison of the effects of filtration and preservation methods on analyses for strontium-90 in ground water. AB - From 1952 to 1988, about 140 curies of strontium-90 were discharged in liquid waste to disposal ponds and wells at the INEL (Idaho National Engineering Laboratory). Water from four wells was sampled as part of the U.S. Geological Survey's quality-assurance program to evaluate the effects of filtration and preservation methods on strontium-90 concentrations in ground water at the INEL. Water from each well was filtered through either a 0.45- or a 0.1-micrometer membrane filter; unfiltered samples also were collected. Two sets of filtered and two sets of unfiltered water samples were collected at each well. One of the two sets of water samples was field acidified.Strontium-90 concentrations ranged from below the reporting level to 52+/-4 picocuries per liter. Descriptive statistics were used to determine reproducibility of the analytical results for strontium-90 concentrations in water from each well. Comparisons were made with unfiltered, acidified samples at each well. Analytical results for strontium-90 concentrations in water from well 88 were not in statistical agreement between the unfiltered, acidified sample and the filtered (0.45 micrometer), acidified sample. The strontium-90 concentration for water from well 88 was less than the reporting level.For water from wells with strontium-90 concentrations at or above the reporting level, 94 percent or more of the strontium-90 is in true solution or in colloidal particles smaller than 0.1 micrometer. These results suggest that changes in filtration and preservation methods used for sample collection do not significantly affect reproducibility of strontium-90 analyses in ground water at the INEL. PMID- 24234032 TI - Analysis of Cdk5-related phosphoproteomics in growth cones. AB - Neurons establish interactions with target cells via elongation and guidance of axons, and the growth cone plays pivotal roles in this process. Cyclin-dependent kinase 5 (Cdk5)is a key regulator of nervous system development. Cdk5 regulates several significant events by phosphorylating substrates that are involved in neurogenesis, and previous studies of Cdk5 have typically focused on single substrates. Here, we took anew approach to investigate Cdk5 substrates using mass spectrometry and bioinformatics analyses. Axonal growth cones were isolated and analyzed by HPLC-MALDI-MS/MS. In total, 178,617 MS/MS spectra were detected. Candidates were analyzed by GPS 2.1 and Scansite 3, which predicted that 2,664 and 275 sites, respectively, were potential phosphorylation sites of Cdk5. There were 190 overlapped phosphorylation sites, corresponding to 89 proteins. Those proteins correlated with axonal functions were classified, and two of them were verified using a classic site-specific mutation strategy. This is the first study in which the phosphoproteome of axonal growth cones was identified. The systematic examination of Cdk5 substrates could provide a reference for further study of molecular mechanisms of axonal growth cones, and new insights into treatments of neuronal disorders. PMID- 24234035 TI - Native American casino gambling in Arizona: A case study of the Fort McDowell reservation. AB - Since Congress passed the American Indian Gambling Regulatory Act (IGRA) in 1988, there has been an explosion in the number of gambling casinos located on Native American reservations. It is estimated that in 1994 the total net revenue from 81 Native American casinos exceeded $2.3 billion dollars. As the number of Native American casinos grows along with the volume of gambling activity, opposition increases from states, the established gambling industry hurt by lost revenues, and groups with moral objections to gambling. This article reports on an effort to measure the economic impact of the Fort McDowell casino located near Phoenix, Arizona. The article discusses the casino's history and current operations. Next, it explains the use of an input-output model to compute the impact of casino's income and employment effects on the economy of Maricopa County. It is estimated that the casino is responsible for 2,483 new jobs, and an increase of approximately $80.35 million in regional output. Additional information is necessary to more accurately assess both the benefits and costs of the casino. Unfortunately, subsequent efforts to collect additional data have been unsuccessful. The conclusion discusses why, and raises questions regarding Native American gaming. PMID- 24234033 TI - Silencing of Hsp90 chaperone expression protects against 6-hydroxydopamine toxicity in PC12 cells. AB - Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder that has been shown to be associated with oxidative stress. This phenomenon occurs primarily via generation of 6-hydroxydopamine(6-OHDA) in catecholaminergic neurons leading to activation of apoptosis. The 90-kDa heat shock protein (Hsp90) functions as a chaperone in maintaining the functional stability and viability of cells under a transforming pressure. Since Hsp90 binds to inactive transcription factor heat shock factor-1 (HSF-1), inhibition of Hsp90 could activate HSF-1 and transcription of heat shock element containing genes subsequently, like Hsp70 as an anti-apoptotic factor. Our trial of silencing Hsp90 expression through transfection of Hsp90 siRNAs into neuronal PC12 cells being exposed to 6-OHDA resulted in the inhibition of pro-apoptotic factors, Bax, caspase-3, and PARP and upregulation of anti-apoptotic factor, Bcl2. In this manner,our data suggest a protective role for Hsp70 as it was observed to be induced upon Hsp90 knockdown. Furthermore, our results showed that Hsp90 silencing against 6-OHDA-induced oxidative stress may associate with upregulation of nuclear factor-erythroid 2-related factor 2. In summary, we found that silencing of Hsp90 expression leads to induction of cytoprotective pathways which can protect neurons against apoptosis in a PD model. PMID- 24234036 TI - Voluntary turnover among non-supervisory casino employees. AB - As gaming is expanding nationally and internationally, existing gaming operations are facing increased competition for employees with gaming experience. This study investigates the factors related to employee turnover in the gaming industry. Workers of six casinos in Reno, Nevada were surveyed concerning their work attitudes and turnover intentions, resulting in a sample of 492 observations. The sample represents all non-supervisory job types typically found in casinos. Pearson correlations and multivariate regression analysis were employed to investigate the relationships among turnover intentions and job satisfaction, specific satisfaction dimensions, organizational commitment, worker perceptions, pay, and labor market conditions. The results show that job satisfaction and organizational commitment are most strongly related to turnover. In contrast to previous findings, labor market conditions and pay play only a minor role in an employee's decision to quit. Instead, perceived lack of job security, satisfaction with supervision, and perceived employer concern with employee well being emerge among the most important factors. The results imply that employers in the gaming industry can manage employee turnover by providing effective supervision that is based on employee participation and fair treatment of employees. Training of supervisors, therefore, may be a relatively inexpensive method of controlling employee turnover in casinos. PMID- 24234034 TI - Collagen Q is a key player for developing rational therapy for congenital myasthenia and for dissecting the mechanisms of anti-MuSK myasthenia gravis. AB - Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). We exploited the proprietary NMJ-targeting signals of ColQ to treat congenital myasthenia and to explore the mechanisms of autoimmune myasthenia gravis (MG). Mutations in COLQ cause congenital endplate AChE deficiency (CEAD). First, a single intravenous administration of adeno associated virus serotype 8 (AAV8)-COLQ to Colq-/- mice normalized motor functions, synaptic transmission, and partly the NMJ ultrastructure. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. Second, MuSK antibody positive MG accounts for 5-15 % of MG. In vitro overlay of AChE/ColQ to muscle sections of Colq-/- mice, as well as in vitro plate-binding of MuSK to ColQ, revealed thatMuSK-IgG blocks binding of ColQ to MuSK in a dose-dependent manner. Passive transfer of MuSK-IgG to wild-type mice markedly reduced the size and intensity of ColQ signals at NMJs. MuSK-IgG thus interferes with binding of ColQ to MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and also to reveal underlying mechanisms of anti-MuSK-MG. PMID- 24234037 TI - Gambling and problem gambling among adult Minnesotans: Changes 1990 to 1994. AB - We assess changes in gambling and problem gambling from 1990 to 1994, a period of rapid expansion in gambling availability. Surveys of non-institutionalized adult Minnesotans were conducted in the spring of each year. Problem gambling was assessed using the SOGS-M, the Minnesota revision of the South Oaks Gambling Screen. Gambling was found to be more frequent among Minnesotans in 1994 than in 1990, and the preference for games changed. Moreover, problem gambling increased over the period. This increase, however, appears to have occurred at the lower ends of the problem gambling continuum rather than at the probable pathological level. Policy implications are explored. PMID- 24234038 TI - Gambling behavior of adolescent gamblers. AB - An adolescent version of the South Oaks Gambling Screen was administered to 965 high school students, aged 14 to 19 years, in the city of Windsor, Ontario. Ninety percent of the adolescents were involved in gambling activities and a substantial proportion of these were engaged in underage gambling. High levels of problem gambling behaviors were found. Problem gambling behaviors were found to be related to the number of different gambling activities and the amount of money gambled. Problem gambling was defined as a score of five or more on the SOGS-RA screen utilizing a scoring method that paralleled the SOGS scoring method. Problem gambling levels were estimated to be 8.1%+/-1.8% of the adolescent sample. There were significant gender differences in the level of problem gambling, but no significant difference with age was found. PMID- 24234039 TI - Casino gambling in private school and adjudicated youngsters: A survey of practices and related variables. AB - This study provides additional information about casino gambling practices in two adolescent samples. Specifically, 109 adolescents from a religious high school and 84 adolescents from a juvenile detention facility in Las Vegas, Nevada were surveyed. Of these, 71 (36.8%) were found to gamble regularly (58 males, 13 females, mean age 15.9 years). Results indicated many similarities among the two groups. The overall sample appeared to have a strong affinity for casino gambling, were diverse in their practices and reasons for gambling, reported a variety of emotional and physiological behaviors when gambling, occasionally experienced problems from casino gambling, and had parents who generally approved and were aware of their children's gambling behavior. The accessibility and family-oriented nature of many new casinos may be responsible for these effects. PMID- 24234040 TI - Expression of tumor necrosis factor-alpha and vascular endothelial growth factor in different zones of fetal membranes: a possible relation to onset of labor. AB - This study aimed to explore whether the altered expression of tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and apoptotic changes in mid zone (MZ) and rupture zone (RZ) of fetal membranes (FM) are regulatory mechanisms associated with labor at term. Fifteen FM specimens were collected after vaginal deliveries and 13 specimens after elective caesarian section. Histological and immunohistochemical analysis were employed. Area percent of TNF-alpha and VEGF immunostaining and apoptotic index (AI) were evaluated using image analysis. The statistical data revealed significantly higher area % for TNF-alpha, VEGF immunoexpression and AI in labor compared to non-labor specimens (p < 0.0001). There was a significantly higher percentage of TNF-alpha immunoexpressed area in MZ compared with RZ in both groups (p < 0.0001). VEGF expression in RZ of both groups proved nearly double or triple the area % of expression relative to MZ with highly significant difference (p < 0.0001). quantitative analysis revealed near two fold increase in the AI in RZ (13.42% +/- 1.2 in labor; 11.20% +/- 0.96 in non-labor groups) when compared to MZ (7.20% +/- 0.6 in labor; 5.08% +/- 0.76 in non-labor groups) with highly significant zonal difference (p < 0.0001). Correlation analysis revealed significant correlation between apoptotic indices and area % of TNF-alpha (r = 0.575, p = 0.002 in non-labor; r = 0.652, p < 0.0001 in labor) and VEGF (r = 0.795, p < 0.0001 in non-labor; r = 0.668, p < 0.0001 in labor). In conclusion, Apoptosis may be regulated by TNF-alpha and VEGF expression in FM at labor. MZ is a step back from RZ and could participate actively in rupture of the FM during labor. TNF-alpha and VEGF increase with onset of labor and differentially expressed in the RZ and the MZ. These findings call for further study with tissue cultures or animal models. PMID- 24234041 TI - Testing the limits of optimality: the effect of base rates in the Monty Hall dilemma. AB - The Monty Hall dilemma is a probability puzzle in which a player tries to guess which of three doors conceals a desirable prize. After an initial selection, one of the nonchosen doors is opened, revealing that it is not a winner, and the player is given the choice of staying with the initial selection or switching to the other remaining door. Pigeons and humans were tested on two variants of the Monty Hall dilemma, in which one of the three doors had either a higher or a lower chance of containing the prize than did the other two options. The optimal strategy in both cases was to initially choose the lowest-probability door available and then switch away from it. Whereas pigeons learned to approximate the optimal strategy, humans failed to do so on both accounts: They did not show a preference for low-probability options, and they did not consistently switch. An analysis of performance over the course of training indicated that pigeons learned to perform a sequence of responses on each trial, and that sequence was one that yielded the highest possible rate of reinforcement. Humans, in contrast, continued to vary their responses throughout the experiment, possibly in search of a more complex strategy that would exceed the maximum possible win rate. PMID- 24234042 TI - Perceptions of intragroup rejection and coping strategies: malleable factors affecting Hispanic adolescents' emotional and academic outcomes. AB - Understanding psychosocial factors that affect the academic achievement of Hispanic adolescents remains a nationwide priority in the United States. Extending previous studies of the stressful effects of perceived discrimination, this year-long longitudinal study examined the correlates of perceived ethnic in group rejection, coping strategies and fatalistic beliefs, on depressive symptoms, grades, and college aspirations of 2,214 Hispanic adolescents (54% female) in Southern California. Based on the transactional model of stress and coping and on self-perception theory, structural equation models revealed that high perceived intragroup rejection (10th grade) and low levels of active coping (11th grade) were associated with depressive symptoms in 11th grade. Also, depressive symptoms partially mediated the link between intragroup rejection and both academic outcomes. Avoidant coping strategies (e.g., watching TV) also predicted depressive symptoms and were positively related to fatalism. In addition, fatalism was negatively related to grades and aspiration to attend college. The findings suggest the need to help adolescents find adequate outlets for communication and to create awareness about the potential effects of intragroup rejection. PMID- 24234044 TI - Preschool prediction: Orthographic and phonological skills, and reading. AB - Because of the research demonstrating the roles of phonological awareness, serial naming speed, and orthographic processing in reading, a test of each of these skills was added to a preschool screening battery. The main aim of the study was to determine whether these measures would contribute to the prediction of reading. The 118 subjects were first tested six months before kindergarten entry and were followed up 19 and 24 months later. Each additional screening test made a significant, independent contribution to the prediction of early first grade word reading/spelling, after the contributions of a parent rating of preschool reading ability (PRA), verbal IQ, socio-economic status (SES), and chronological age were accounted for. With letter naming and PRA, the additional tests were responsible for 62 percent of the variance. The orthographic test made the largest single contribution (32%) to the variance in word reading/spelling.Variables contributing significantly to the prediction of later first grade reading comprehension were (in order of proportion of the variance accounted for) letter naming, sentence memory, object naming speed, the orthographic test, and SES. The revised preschool screening battery correctly identified 91 percent of individual first grade good and poor readers. It was concluded that preschool measures of phonological awareness, serial naming speed, and orthographic processing make a strong contribution to prediction of first grade reading. PMID- 24234043 TI - Cystatin B and SOD1: protein-protein interaction and possible relation to neurodegeneration. AB - Cystatin B (CSTB), an inhibitor of the cysteine proteases, belongs to the cathepsin family and it is known to interact with a number of proteins involved in cytoskeletal organization. CSTB has an intrinsic tendency to form aggregates depending on the redox environment. The gene encoding for CSTB is frequently mutated in association with the rare neurodegenerative condition progressive myoclonus epilepsy. Increased levels of CSTB have been observed in the spinal cord of transgenic mice modeling SOD1-linked familial amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motoneurons. In the present study, we have investigated the relationship occurring between the expression of SOD1 and CSTB either wild-type or double-cysteine substitution mutant (Cys 3 and Cys 64). Whether or not there is a physical interaction between the two proteins was also investigated in overexpression experiments using a human neuroblastoma cell line and mouse-immortalized motoneurons. Here we report evidences for a reciprocal influence of CSTB and SOD1 at the gene expression level and for a direct interaction of the two proteins. PMID- 24234045 TI - Training phonological awareness: A study with inner-city kindergarten children. AB - A small-scale, longitudinal, phonological awareness training study with inner city kindergarten children was conducted in four classrooms. The central goals of the study were the creation and evaluation of a phonological awareness training program and a preliminary look at the consequence of that training on basic phonological processes.Assessment of phonological awareness and basic phonological processes was carried out in the fall of the kindergarten year, and again in the spring following an 18 week training program which incorporated both auditory and articulatory techniques for fostering metaphonological development. Follow-up evaluation of promotion to first grade and of reading achievement took place a year later. The children in the two experimental classes receiving training had significantly greater gains in phonological awareness at the end of kindergarten, were significantly more likely to be promoted to first grade rather than to pre-one, and had a trend toward better reading skills in first grade than did the smaller group of children promoted to first grade from the control classes. In addition, there were some indications that development of phonological awareness was accompanied by changes in the underlying phonological system as well. Here we focus on the rationale and implementation of our training program and discuss the implications of the findings for a potential large-scale study. PMID- 24234046 TI - Stimulating basic reading processes using auditory discrimination in depth. AB - Recent research indicates that a major cause of reading (decoding) disabilities lies in an inability to manipulate speech at its phonemic (phonological) level. The Auditory Discrimination in Depth Program (ADD Program), stimulates basic phonological awareness and has been used extensively at The Reading Foundation in Calgary, Alberta. Here we present pre- and post-test data from 281 clients (ranging from school-age through adulthood) seen over a two-year period; post test data was collected after 80 hours of ADD instruction. To assess whether significant gains had been achieved, an analysis of covariance was performed, covarying for age and initial vocabulary scores. After 80 hours of intensive instruction, highly significant gains (p<.001) were evident on measures of phonological awareness, sound/symbol connections, word identification, spelling, and decoding in context. In addition to the treatment effect, age and vocabulary had some influence on some of the variables. The data was also analyzed to determine whether the results went beyond a "group effect" only. A total of 229 cases were tabulated for gains or losses on the word attack subtest and on the reading and spelling subtests of the WRAT-R. Results indicate that the remediation was effective for all subjects, though gains on spelling tended to be less than on the two reading scores. PMID- 24234047 TI - The missing foundation in teacher education: Knowledge of the structure of spoken and written language. AB - Reading research supports the necessity for directly teaching concepts about linguistic structure to beginning readers and to students with reading and spelling difficulties. In this study, experienced teachers of reading, language arts, and special education were tested to determine if they have the requisite awareness of language elements (e.g., phonemes, morphemes) and of how these elements are represented in writing (e.g., knowledge of sound-symbol correspondences). The results were surprisingly poor, indicating that even motivated and experienced teachers typically understand too little about spoken and written language structure to be able to provide sufficient instruction in these areas. The utility of language structure knowledge for instructional planning, for assessment of student progress, and for remediation of literacy problems is discussed.The teachers participating in the study subsequently took a course focusing on phonemic awareness training, spoken-written language relationships, and careful analysis of spelling and reading behavior in children. At the end of the course, the teachers judged this information to be essential for teaching and advised that it become a prerequisite for certification. Recommendations for requirements and content of teacher education programs are presented. PMID- 24234048 TI - Evidence for and characteristics of Dyslexia among Japanese children. AB - In an attempt to determine the extent of developmental dyslexia in Japan, an oral reading test and a modified Bangor Dyslexia Test were administered to 125 fourth graders (69 boys and 56 girls). In this sample, four boys and four girls (6%) qualified as dyslexic, challenging the wide-spread belief that dyslexia is largely absent among Japanese children. Here we describe some characteristics of these Japanese dyslexics. PMID- 24234049 TI - Developmental dyslexia: Heterogeneity without discrete subgroups. AB - Is the dual route model of word recognition useful in explaining individual differences in reading behaviors for most developmental dyslexics? Many past case studies of surface and phonological acquired dyslexics and a few similar studies of developmental dyslexia have suggested this might be so. The present study investigated individual differences among a group of 65 dyslexics, age 10 to 13, in reading, phonemic segmentation, and word retrieval. The dyslexics' performance was compared to that of 65 reading age controls and 17 age-matched good readers. The research questions were: (1) Are there discrete subgroups of developmental dyslexics as suggested by the case studies? (2) How do oral language measures relate to the various reading tasks? The data indicated there were no discrete subgroups within the group of dyslexics; in addition, the variability in performance on reading tasks was quite similar for the dyslexic and reading age control groups. A few dyslexics resembled phonological dyslexics and surface dyslexics, but these subjects were still part of a continuum. We also report the relationship between phonemic segmentation and word retrieval and various reading tasks. It appears that dyslexics at extreme ends of the continuum may exhibit quite different patterns from each other in their oral language task performance as well as in their reading. PMID- 24234050 TI - Comparison of deficits in cognitive and motor skills among children with dyslexia. AB - There is a growing body of evidence that children with dyslexia have problems not just in reading but in a range of skills including several unrelated to reading. In an attempt to compare the severity and incidence of deficits across these varied domains, children with dyslexia (mean ages 8, 12, and 16 years), and control groups of normally achieving children matched for IQ and for age or reading age, were tested on a range of primitive (basic) skills. The children with dyslexia performed significantly worse than the same-age controls on most tasks, and significantly worse even than the reading-age controls on phoneme segmentation, picture naming speed, word tachistoscopic word recognition, speeded bead threading and some balance tasks. The overall performance of the children with dyslexia is interpreted as showing less complete automatization than normal. PMID- 24234051 TI - On the differential diagnosis of reading, attentional and depressive disorders. AB - Children may present with reading and/or attentional and/or affective (depressive) disorders in childhood. Although reading problems are more readily identifiable, childhood attentional and affective disorders can be difficult to recognize and diagnose. Here are discussed a number of complex and potentially confusing ways in which reading, attentional and affective disorders may be related: a primary problem in one area may result in problems in another; one disorder may look like another; and/or a child may simultaneously present two or all three primary disorders. Current clinical practice and recent and ongoing research is presented to clarify the changing definitions and potential relationships of these three childhood disorders to aid the process of differential diagnosis. PMID- 24234052 TI - Dyslexia and musical notation. AB - The authors examine the difficulties experienced by dyslexic musicians in the formalized study of music, in particular, musical notation. They describe case studies from the literature and from personal interviews they conducted with musicians about their educational histories, musical weaknesses and strengths, and successful compensatory strategies. The authors make instructional suggestions for educators and musicians with dyslexia on how to use multisensory approaches to teach musical notation. PMID- 24234053 TI - Dyslexia in adults: Evidence for deficits in non-word reading and in the phonological representation of lexical items. AB - Difficulties in reading and language skills which persist from childhood into adult life are the concerns of this article. The aims were twofold: (1) to find measures of adult reading processes that validate adults' retrospective reports of difficulties in learning to read during the school years, and (2) to search for indications of basic deficits in phonological processing that may point toward underlying causes of reading difficulties. Adults who reported a history of difficulties in learning to read (n=102) were distinctly disabled in phonological coding in reading, compared to adults without similar histories (n=56). They were less disabled in the comprehension of written passages, and the comprehension disability was explained by the phonological difficulties. A number of indications were found that adults with poor phonological coding skills in reading (i.e., dyslexia) have basic deficits in phonological representations of spoken words, even when semantic word knowledge, phonemic awareness, educational level, and daily reading habits are taken into account. It is suggested that dyslexics possess less distinct phonological representations of spoken words. PMID- 24234054 TI - Life adjustments of college freshmen with and without learning disabilities. AB - This paper reports the results of a study comparing college freshmen with learning disabilities (LD) and freshmen with no learning disabilities (NLD). Four data collections over one academic year were completed on a total of 72 students (LDn=39; NLDn=33). Results of the study indicated differences between groups in their initial choice of living accommodations and in the changes made over the year: the overall trend was for students with LD to become more dependent on their families, while students with NLD were becoming less dependent on their families. With regard to academics, students with LD reported spending significantly less time in study and course preparation, as well as greater pessimism about success in coursework. Despite their pessimism, the actual GPA attainment of students with LD was similar to that of NLD peers. Whereas both groups initially predicted it would be easy to adjust to the academic and social nature of college, students with learning disabilities ultimately reported being dissatisfied with the social climate on campus. No differences were found between LD and NLD students regarding their motivation for attending college, or their plans for final degree attainment. PMID- 24234055 TI - How do illiterate adults react to metalinguistic training? AB - The present study focuses on the capacity of illiterate adults to master three different metalinguistic tasks: judgment of phonological length of words, initial consonant deletion, and lexical segmentation of sentences. Illiterates' performance, during a pre-test and after training, was compared with that of literates and partial illiterates (adults at the beginning of the process of acquiring literacy) who received the same training. In the pre-test, illiterates were lower than literates in the three tasks; and partial-illiterates were at an intermediate level in two of the tasks. The three groups profited from the training, especially illiterates and partial-illiterates for whom improvement was dramatic across all three tasks. Finally, the results revealed a hierarchy of difficulty across the tasks. The capacity to focus on the phonological dimension seemed to be a prerequisite for the phoneme deletion ability. The task of lexical segmentation seemed to be more a measure of syntactic awareness than a measure of phonological awareness. PMID- 24234056 TI - Instructional strategies for long-term success. AB - Through a qualitative research study we developed a model of employment success based on the experiences of successful adults with learning disabilities. This model may be particularly useful to students with learning disabilities in helping them experience success both in school and beyond. We suggest that the components of the model-internal decisions comprising desire, goal orientation, and reframing, and external manifestations or behaviors of persistence, goodness of fit, learned creativity, and favorable social ecologies-can be systematically taught and then used. By focusing on what has worked for adults with learning disabilities, we propose that the model taps into inherent strengths that can compensate for significant limitations associated with learning disabilities. The model does not guarantee success, but it does equip students with learning disabilities with a readiness to capitalize on opportunities that they might otherwise miss. PMID- 24234057 TI - Foreword. PMID- 24234058 TI - Propolis protects against high glucose-induced vascular endothelial dysfunction in isolated rat aorta. AB - While propolis is known to have abundant bioactive constituents and a variety of biological activities, it is not clear whether propolis has beneficial effects on high glucose-mediated vascular endothelial impairment. The aim of the present study was to investigate the potential protective effect of propolis extract against the acute vascular endothelial dysfunction resulting from exposure to high glucose load and to elucidate its underlying mechanism. Rat aortic rings were incubated with normal glucose (11 mM), high glucose (44 mM), or mannitol (44 mM) for 3 h with or without propolis extract (400 MUg/ml). Contraction to phenylephrine (Phe, 10(-9)-10(-5) M) and relaxation to acetylcholine (ACh, 10(-9) 10(-5) M) and sodium nitroprusside (SNP, 10(-9)-10(-5) M) were measured before and after incubation. Changes in malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were also measured. Phe-induced contraction was impaired by high glucose as the E(max) decreased from 138.87 +/- 11.43 to 103.65 +/- 11.5 %. In addition, ACh-induced relaxation was impaired as the E(max) decreased from 99.80 +/- 7.25 to 39.20 +/- 6.5 %. SNP-induced relaxation was not affected. Furthermore, high glucose decreased the levels of both SOD (by 6 U/ml) and GSH (by 68 %) and increased levels of MDA (by 85 %). Propolis extract prevented high glucose-induced impairment of Phe and ACh responses and increased both SOD and GSH, leading to decreased MDA levels. In conclusion, propolis can protect against high glucose-induced vascular dysfunction by reducing oxidative stress. PMID- 24234059 TI - Antignawing factor of crude oil derived fromThujopsis dolabrata S. et Z. var.hondai sawdust against mice. AB - The antignawing activity of the steam distillate ofThujopsis dolabrata S. et. Z. var.hondai sawdust against mice was evaluated using a wire-dipping method. This method is suitable for measuring repellent activities of chemicals and plant derived materials. The steam distillate of theThujopsis sawdust was shown to have potent antignawing activity. Three terpenoid compounds with antignawing activity were isolated from the steam distillate of theThujopsis sawdust: thujopsene, carvacrol, andbeta-thujaplicine. Carvacrol exhibited the most potent repellent activity. As a naturally occurring repellent, carvacrol could be useful as new preventive agent against various kinds of damage caused by rodents. PMID- 24234060 TI - Developmental stage of herbivorePseudaletia separata affects production of herbivore-induced synomone by corn plants. AB - The female parasitic waspCotesia kariyai discriminated between the volatiles of corn leaves infested by younger host larvaePseudaletia separata (first to fourth instar) and uninfested leaves in a Y-tube olfactometer; the wasps were attracted to the infested leaves. In contrast, when corn plants were infested by the later stages (fifth and sixth instar) of the armyworm, the wasps did not distinguish between infested corn leaves and uninfested corn leaves in the olfactometer. Mechanically damaged leaves were no more attractive than undamaged leaves, and host larvae or their feces were not attractive to the parasitoid. Through chemical analysis, the herbivore-induced plant volatiles were identified in the headspace of infested corn leaves. The herbivore-induced volatiles (HIVs) constituted a larger proportion of the headspace of corn leaves infested by early instar armyworms than of corn leaves infested by late instar armyworms. Application of third-instar larval regurgitant onto artificially damaged sites of leaves resulted in emission of parasitoid attractants from the leaf, whereas leaves treated with sixth-instar regurgitant did not. The function of this herbivore-stage related specificity of herbivore-induced synomones is discussed in a tritrophic context. PMID- 24234061 TI - Effect of phytotoxic resin glycoside on activity of H(+)-ATPase from plasma membrane. AB - A resin glycoside mixture isolated fromIpomoea tricolor inhibited radicle growth ofEchinochloa crusgalli. The effect of the resin was tested on the activity of the plasma membrane H(+)-ATPase fromE. crusgalli. For this purpose, plasma membrane vesicles were purified by the method of aqueous two-phase partitioning. The resin glycoside inhibited by 30% the activity of the plasma membrane ATPase. The same result was obtained with the purified main component of the resin. This indicates that the plasma membrane ATPase can be one of the cellular targets of the resin. Hence it is possible that the mechanism of action of the resin involves an inhibition of the plasma membrane ATPase. PMID- 24234062 TI - Sex attractants of geometrid and noctuid moths: Chemical characterization and field test of monoepoxides of 6,9-dienes and related compounds. AB - (Z,Z)-6,9-Dienes with straight C18-C23 chains were synthesized from linoleic acid, and a C17 chain was synthesized by hydrogenation of the corresponding 6,9 diyne prepared from propargyl alcohol. Oxidation of the homoconjugated dienes withm-chloroperoxybenzoic acid yielded a 1:1 mixture of two monoepoxides that could be separated by repeated medium-pressure liquid chromatography with a Lobar column. The chemical structure of each positional isomer was confirmed by analyses of the ozonolysis products, and the isomers showed characteristic(13)C signals in their NMR spectra and fragment ions in their EI mass spectra. In addition to the (Z,Z,Z)-3,6,9-trienes with straight C18-C23 chains and their monoepoxides, field tests using single source lures incorporating one of the above seven dienes and 14 monoepoxymonoenes were carried out in a forest in Tokyo from 1992 to 1994. Consequently, attraction of six geometrid species and five noctuid species was observed for the first time. PMID- 24234063 TI - Identification of sensilla involved in taste mediation in adult western corn rootworm (Diabrotica virgifera virgifera LeConte). AB - A group of sensilla present on the maxillary galea of adult western corn rootworm,Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) beetles has been identified morphologically and physiologically to be involved in taste mediation. There are approximately 15 chemosensory hairs on each galea. Bilateral removal of these structures resulted in a significantly reduced consumption of a strongly phagostimulant triterpenoid, cucurbitacin B, and led to increased ingestion of a phagodeterrent alkaloid, strychnine. Electrophysiological responses obtained via tip-recording of galeal chemosensilla with submillimolar concentrations of host and nonhost plant compounds resulted in dose responses overlapping with the effective behavioral ranges. Cucurbitacin B was found to evoke chemosensory responses at levels as low as 0.1uM. Sincegamma aminobutyric acid (GABA) is an agonist. (-)-beta-hydrastine and strychnine are antagonists, and cucurbitacin B has been proposed to act at a separate modulatory site of classical synaptic GABA and glycine receptor-channel complexes, results reported here raise the possibility that there are peripheral chemosensory receptor sites that may resemble, functionally and structurally, synaptic receptor sites in the central nervous system. PMID- 24234064 TI - Outdoor attractancy of males ofMatsucoccus josephi (Homoptera: Matsucoccidae) andElatophilus hebraicus (Hemiptera: Anthocoridae) to synthetic female sex pheromone ofMatsucoccus josephi. AB - The active component of the sex pheromone ofMatsucoccus josephi is (2E,6E,8E)-5,7 dimethyl-2,6,8-decatrien-4-one; the chemical is also a powerful kairomone of adult males and females of the bugElatophilus hebraicus the principal predator ofM. josephi. The presence of theZ isomer (2E,6Z,8E)-5,7-dimethyl-2,6,8-decatrien 4-one does not interfere with the attractancy of the activeE component forM. josephi males or the bug. Our results show a clear dose-response between trap catch ofM. josephi males andE. hebraicus. Conversely, increasing amounts of theZ isomer in the mixture did not affect the attraction of the scale insect males or the bug. The catch ofM. josephi males did not differ significantly among traps of different color, and was significantly higher with traps attached to the tree trunk than those suspended between trees. Comparison of the catch ofM. josephi among the three forests and between pine species suggests that the level of infestation ofPinus halepepsis andPinus brutia ssp.brutia is similar, despite the fact that the latter pine is resistant to the scale insect. Both sexes ofE. hebraicus were trapped in much lower numbers at the more infested sites. This may be related to interference with the activity ofE. hebraicus due to deterioration and drying of parts of the tree crowns and heavy colonization by generalist predators in injured trees. PMID- 24234065 TI - Leaf profile of maize resistance factors to European corn borer,Ostrinia nubilalis. AB - The feeding preference of European corn borer larvae for immature whorl tissue of maize was examined by conducting leaf bioassays and quantifying resistance factors along the length of mid-whorl leaves from the maize synthetic BS9(C4) developed by recurrent selection for resistance. Potential resistance factors that were quantified included percent foliar nitrogen, gravimetric determination of soluble metabolites and fiber, soluble phenolics and hydroxamic acids, cell wall-bound phenolics, leaf toughness, and UV absorbance of the epidermal cell wall determined by microspectrophotometry. Larvae consumed immature tissue at a higher rate than more mature tissue outside of the whorl, despite higher levels of DIMBOA in immature tissue. Consumption rate was highly negatively correlated with epidermal cell wall absorbance and leaf toughness. Fiber content and phenolic fortification of cell walls are proposed as the major resistance components that influence European corn borer feeding preference within the resistant synthetic BS9(C4). PMID- 24234066 TI - Controlled-release pheromone dispenser for use in traps to monitor flight activity of false codling moth. AB - Field trials were conducted in the western Cape Province, South Africa, to develop a sex pheromone dispenser suitable for monitoring the flight activity of false codling moth. A controlled-release dispenser capable of releasing sex pheromone at a predetermined and constant release rate without replacement for more than seven months was produced. PMID- 24234067 TI - Hydrocarbon dynamics within and between nestmates inCataglyphis niger (Hymenoptera: Formicidae). AB - The objective of the present study was to evaluate the interrelationship between the cuticular and postpharyngeal glands' hydrocarbons, both in the individual ant and during its interaction with nestmates. In vivo radiochemical assays were employed to monitor the de novo hydrocarbon biosynthesis from acetate in the ant's body. The newly synthesized hydrocarbons appeared first internally and after 24 hr they accumulated in the postpharyngeal gland and on the cuticular surface. Blocking the possibility of external transfer of hydrocarbons between cuticle and postpharyngeal gland led to a significant decrease of labeled hydrocarbons in the postpharyngeal gland. In addition, during encounters between labeled and unlabeled ants, newly synthesized hydrocarbons were transferred, mainly via trophallaxis, but also by allo-grooming and physical contact. In view of these results, we propose as a model for their dynamics that hydrocarbons are synthesized in tissues associated with the integument. Through self-grooming, there is a constant exchange of hydrocarbons between the cuticular surface and the postpharyngeal gland. Furthermore, in encounters between nestmates, hydrocarbons are exchanged among them mostly by trophallaxis, with the mediation of the postpharyngeal gland. Thus, this gland acts as a pool for mixing colonial hydrocarbons and may serve to attain a unified colony odor. PMID- 24234068 TI - On insect attractants from pitcher plants of the genusHeliamphora (sarraceniaceae). AB - Examination ofHeliamphora heterodoxa andH. tatei from the Guayana Highlands of Venezuela reveals that the enol diacetal monoterpene, sarracenin, is the major volatile compound present in the spoon-shaped structures of leaves of the pitchers. In addition, erucamide, phenol, cinerone, phenylacetaldehyde, and a series of methyl esters also occur in extracts of the spoon-shaped appendages of pitchers at the time during which they attract insects. PMID- 24234069 TI - Registries, diagnostic studies, and therapeutic interventional trials: generating evidence in a broad perspective. PMID- 24234070 TI - Comprehensive testing for, and diagnosis of, sexually transmissible infections among Australian gay and bisexual men: findings from repeated, cross-sectional behavioural surveillance, 2003-2012. AB - OBJECTIVES: To analyse changes in testing for sexually transmissible infections (STI) among gay and bisexual men in Melbourne, Sydney and Queensland, Australia, particularly comprehensive STI testing (at least four tests from different anatomical sites in the previous year), and the characteristics of men who had such testing. METHOD: Data were analysed from repeated, cross-sectional, community-based surveys conducted during 2003-2012. Trends in specific STI tests and comprehensive testing were assessed and the characteristics of participants who reported comprehensive STI testing were identified using multivariate logistic regression, stratified by HIV status. RESULTS: Among HIV-negative and unknown status men (n=51 009), comprehensive STI and HIV testing increased substantially from 13% in 2003 to 34% in 2012. During the same period, comprehensive STI testing (excluding HIV testing) increased from 24% to 57% among HIV-positive men (n=5532). In both HIV status groups, comprehensive testing was more commonly reported by men who had unprotected anal intercourse with casual partners, and men with higher numbers of partners. Among HIV-negative/unknown status participants, comprehensive STI and HIV testing was also associated with education level, regional location and finding partners online. Among HIV positive men, comprehensive STI testing was also associated with free time spent with gay men and illicit drug use. Comprehensive testing was related to a high annual rate of diagnosis with STIs (20% of HIV-negative/unknown status men and 38% of HIV-positive men). CONCLUSIONS: There has been a substantial improvement in the proportion of gay and bisexual men in Melbourne, Sydney and Queensland who report comprehensive testing. Comprehensive testing is most likely among men whose practices put them at increased risk of infection, and is associated with a high rate of STI diagnosis. However, opportunities for comprehensive testing are still being missed, suggesting a need for its ongoing promotion. PMID- 24234071 TI - Use of Chlamydia trachomatis high-resolution typing: an extended case study to distinguish recurrent or persistent infection from new infection. AB - OBJECTIVES: Repeated infections of Chlamydia trachomatis may be new infections or persistent infections due to treatment failure or due to unresolved infections in sexual partners. We aimed to establish the value of using high-resolution multilocus sequence typing (CT-MLST) to discriminate repeated C trachomatis infections. METHODS: Paired C trachomatis positive samples (baseline (T0) and after 6 months (T1)) were selected from two Dutch screening implementation studies among young heterosexual people. Typing with six CT-MLST loci included the ompA gene. The uniqueness of strains was assessed using 256 reference CT-MLST profiles. RESULTS: In 27 out of 34 paired cases, full sequence types were obtained. A multilocus (13 cases) or single locus variant (4 cases) was seen, indicating 17 new C trachomatis infections at T1. The ompA genovar was identical for 5 of 17 discordant cases. The 10 cases with concordant typing results were categorised as treatment failure (5 cases) versus persistent or recurrent infections (5 cases). Surprisingly, these concordant cases had C trachomatis strains that were either unique or found in small clusters. The median time between T0 and T1 did not differ between the concordant and discordant cases. CONCLUSIONS: High-resolution typing was superior in discriminating new infections compared with only using ompA genovar typing. Many cases (37%) showed exactly the same C trachomatis strain after 6 months. CT-MLST is not conclusive in distinguishing recurrent infections from treatment failure. PMID- 24234072 TI - Recent partner violence and sexual and drug-related STI/HIV risk among adolescent and young adult women attending family planning clinics. AB - BACKGROUND/OBJECTIVES: Adolescent and young adult women are at high risk for sexually transmitted infections (STIs)/HIV and intimate partner violence (IPV). We evaluate the prevalence of IPV in the past 3 months and its associations with STI/HIV risk, STI and related care-seeking over the same time period. METHODS: Female family planning clinic patients ages 16-29 years (n=3504) participated in a cross-sectional survey in 2011-2012 as a baseline assessment for an intervention study. We examined associations of recent IPV with sexual and drug related STI/HIV risk behaviour, self-reported STI and STI-related clinical care seeking via logistic regression. RESULTS: Recent physical or sexual IPV (prevalence 11%) was associated with recent sexual and drug-related STI/HIV risk, specifically unprotected vaginal sex (adjusted OR (AOR) 1.93, 95% CI 1.52 to 2.44), unprotected anal sex (AOR 2.22, 95% CI 1.51 to 3.27) and injection drug use, their own (AOR 3.39, 95% CI 1.47 to 7.79) and their partner's (AOR 3.85, 1.91 to 7.75). IPV was also linked with coercive sexual risk: involuntary condom non-use (AOR 1.87 to 95% CI 1.51 to 2.33), and fears of requesting condoms (AOR 4.15, 95% CI 2.73 to 6.30) and refusing sex (AOR 11.84, 95% CI 7.59 to 18.45). STI-related care-seeking was also more common among those abused (AOR 2.49, 95% CI 1.87 to 3.31). CONCLUSIONS: Recent IPV is concurrent with sexual and drug related STI/HIV risk, including coercive sexual risk, thus compromising women's agency in STI/HIV risk reduction. Clinical risk assessments should broaden to include unprotected heterosexual anal sex, coercive sexual risk and IPV, and should promote safety and harm reduction. PMID- 24234075 TI - Introduction. PMID- 24234073 TI - Highly visible street-based HIV rapid testing: is it an attractive option for a previously untested population? A cross-sectional study. AB - BACKGROUND: Given the shortage of community-based HIV testing initiatives in resource-rich countries not targeting most-at-risk populations, we aimed to evaluate whether a highly visible mobile programme promoting and offering rapid HIV testing in the street can attract persons at risk for infection who have never been tested. METHODS: Between 2008 and 2011, the programme served 7552 persons in various Spanish cities who answered a brief questionnaire while awaiting their results. The factors associated with being tested for the first time were analysed using two logistic regression models, one for men who have sex with men (MSM) and the other for only heterosexual men (MSW) and women. RESULTS: 3517 participants (47%) were first-time testers (24% of MSM, 56% of MSW and 60% of women). Among them, 22 undiagnosed HIV infections were detected with a global prevalence of 0.6% and 3.1% in MSM. Undergoing a first HIV test was independently associated with age <30, being from Spain or another developed country, lack of university education, having fewer partners, having had unprotected sex with casual partners and not having been diagnosed with a sexually transmitted infection. In heterosexuals, also with never injected drugs, and in MSM, with not being involved in the gay community. Among those tested for the first time, 22% had never thought of being tested and 62% decided to be tested when they passed by and noticed the programme, regardless of their previous intentions. CONCLUSIONS: This community programme attracted a substantial number of persons previously untested and particularly hard to reach, such as those with low education and MSM who were least involved in the gay community. Programme visibility was a decisive factor for almost two of every three persons who had never been tested. PMID- 24234074 TI - Incorporating elements of social franchising in government health services improves the quality of infant and young child feeding counselling services at commune health centres in Vietnam. AB - BACKGROUND: Although social franchising has been shown to enhance the quality of reproductive health services in developing countries, its effect on nutrition services remains unexamined. This study assessed the effects of incorporating elements of social franchising on shaping the quality of infant and young child feeding (IYCF) counselling facilities and services in Vietnam. METHODS: Process related data collected 12 months after the launch of the first franchises were used to compare randomly assigned Alive & Thrive-supported health facilities (AT F, n = 20) with standard facilities (SF, n = 12) across three dimensions of service quality: 'structure', 'process' and 'outcome' that capture the quality of facilities, service delivery, and client perceptions and use, respectively. Data collection included facility assessments (n = 32), staff surveys (n = 96), counselling observations (n = 137), client exit interviews (n = 137) and in-depth interviews with mothers (n = 48). RESULTS: Structure: AT-F were more likely to have an unshared, well-equipped room for nutrition counselling than SF (65.0% vs 10.0%). PROCESS: Compared with SF providers, AT-F staff had better IYCF knowledge (mean score 9.9 vs 8.8, range 0-11 for breastfeeding; mean score 3.6 vs 3.2, range 0-4 for complementary feeding). AT-F providers also demonstrated significantly better interpersonal communication skills (score 9.6 vs 5.1, range 0-13) and offered more comprehensive counselling sessions. OUTCOME: Overall utilization of franchises was low (10%). A higher proportion of pregnant women utilized franchise services (48.9%), compared with mothers with children 6-23.9 months (1.4%). There was no quantitative difference in client satisfaction with counselling services between AT-F and SF, but franchise users praised the AT-F for problem solving related to child feeding. CONCLUSIONS: Incorporating elements of social franchising significantly enhances the quality of IYCF counselling services within government primary healthcare facilities, particularly their structural and process attributes. Provided that service utilization is improved through demand generation, this model has the potential to impact IYCF practices and child nutrition. PMID- 24234076 TI - Immobilized biocatalysts : The research program at Helsinki University of Technology. AB - Recent work on immobilized biocatalysts at Helsinki University of Technology, Finland, is described, with starch processing, Beta-galactosidase, glucose isomerase, invertase, and the immobilization of live cells as special examples. PMID- 24234078 TI - Immobilized penicillin V acylase : Development of an industrial catalyst. PMID- 24234077 TI - Choosing an enzyme reactor theoretical background and considerations as illustrated in a case study. AB - A short review of different types of enzyme reactors and factors of influence on the reactor choice is given. The background of their kinetic differences is discussed. The conversion of starch to maltose by use of an immobilized two enzyme system has been chosen as a case study. PMID- 24234079 TI - Nonideal flow in tubular reactors : Stochastically distributed ideality. AB - A compact and flexible method for modeling nonideal flow in tubular reactors is presented. The procedure involves dividing the reactor into discrete elements, each being an ideal reactor, but with characteristics of each assigned stochastically. Flow between cells is also shown as a stochastic behavior. The calculation steps are given in case of a fixed-bed reactor with unidirectional flow. PMID- 24234080 TI - A comparison of the formation of intermediary products during lactose hydrolysis with free and immobilized thermophilic lactase. AB - CONCLUSION: Immobilization of the thermophilic lactase causes a decrease in the formation of intermediary products. This means that partially hydrolyzed lactose syrups contain less of these intermediary products when the immobilized thermophilic lactase is used in the hydrolysis process than when a soluble lactase is used. In addition, the decrease in intermediary product formation gives a higher enzyme efficiency in the process. PMID- 24234081 TI - Immobilized plant cells. AB - Plant cells have been immobilized in alginate, where they have been shown to retain their biological activity. Such systems can be utilized for bioconversions. PMID- 24234082 TI - Continuous production of butanol with immobilized cells ofClostridium acetobutylicum. AB - Spores ofClostridium acetobutylicum were immobilized in calcium alginate. An active gel preparation was obtained after outgrowth of the spores to vegetative cells within the gel matrix. A 100 mL column containing the immobilized cells was used for continuous production. At steady-state conditions the productivity of butanol was 67 g/L reactor volume/day. PMID- 24234083 TI - Immobilized cells in microbial nitrate reduction. AB - The microorganismPseudomonas denitrificans was immobilized in alginate. These immobilized cells were capable of reducing 0.8 mg NO 3 (-) /min/g wet weight of cells. PMID- 24234084 TI - Enzymes coimmobilized with microorganisms : The bioconversion of whey permeate to ethanol with Beta-galactosidase andSaccharomyces cerevisiae. AB - The enzyme Beta-galactosidase was coimmobilized with the yeastSaccharomyces cerevisiae in alginate. The coimmobilized system was used to produce ethanol from cheese whey permeate. PMID- 24234085 TI - Production of alpha-keto acids with alginate-entrapped whole cells of the yeastTrigonopsis variabilis. AB - The yeast,Trigonopsis variabilis, was immobilized by entrapment in alginate. The immobilized cells containing high amounts of D-amino acid oxidase were used to convert D-amino acids to their corresponding alpha-keto acids. PMID- 24234086 TI - Citric acid production with alginate bead entrappedAspergillus niger ATCC 9142. AB - Aspergillus niger ATCC 9142 mycelium was entrapped in calcium alginate beads and employed in an air-lift completely stirred reactor for continuous production of citric acid. Maximum yield obtained from 10% (w/v) sucrose was 12 g dm(-3) with about 40% fermentation efficiency. Maximum rate of production 70 mg g(-1) h(-1) was about five times that obtained in classical batch fermentation. PMID- 24234087 TI - Application of magnetic immobilized microorganisms : Ethanol production bySaccharomyces cerevisiae. AB - Magnetic calcium alginate yeast beads, made by incorporation of magnetite or colloidal magnetic liquid, FerrofluidM, exhibited catalytic behavior similar to that of their nonmagnetic counterparts. The magnetic immobilized preparations' shortterm performance, long-term operational stability, and capacity forin situ activation were unaffected by the inclusion of magnetic material. The magnetic quality of the alginate beads provides manipulatory advantages. PMID- 24234088 TI - Affinity precipitation of enzymes. AB - Lactate dehydrogenase has been purified by precipitation with a bis-ligand. The precipitating agent in this case was Bis-NAD. This approach of affinity precipitation is also applicable to other enzymes. PMID- 24234089 TI - Magnetic microspheres for targeting of drugs. AB - Magnetic microspheres were prepared from starch. The microspheres could be crosslinked with various agents, and drugs could be entrapped adsorbed, or covalently coupled to the microspheres. PMID- 24234090 TI - Affinity chromatographic purification of lentil lectin using immobilized yeast cells. AB - A model system for evaluating macroporous supports containing immobilized whole cells in affinity Chromatographic applications is described. Whole cells were immobilized in a polyacrylamide network in a two-step polymerization process. The affinity system discussed consists of immobilized cells ofSaccharomyces cervisiae in the purification of lentil lectin fromLens culinaris. PMID- 24234091 TI - Partition Affinity Ligand Assay (PALA) : A simple binding assay procedure. AB - In a competitive binding assay, the ligand to be quantified competes with a fixed amount of labeled ligand for the sites on a limiting amount of binding protein. The amount of label bound is therefore dependent on the ratio between native and labeled ligand. In a binding assay, one must separate the free ligands from bound. The better the separation, the higher the sensitivity of the assay. But effective methods are often laborious and time-consuming and thus we have developed a novel approach, the Partition Affinity Ligand Assay (PALA). PMID- 24234092 TI - Immunocapillarymigration : Use of fluorescein- and enzyme-labeled antibodies to quantify C-reactive protein. AB - The method is based upon the attachment of antibodies to a porous insoluble support and the subsequent capillary migration of the antigen-containing solution in the support. The antigen-covered area thereby obtained was visualized with fluoresceinor horseradish peroxidase-labeled antibodies. The height of this area increased with increasing antigen concentration. The method was used to quantitate C-reactive protein. PMID- 24234093 TI - A liposome-based assay for quantitation of detergents. AB - The amount of enzyme released from liposomes exposed to detergents varies with the amount of detergent present. This fact makes it possible to quantitate the detergent. Multilamellar liposomes containing entrapped peroxidase were adsorbed to paper discs and then exposed to solutions containing detergents. The assay procedure proved useful for assaying detergents down to their critical micelle concentration (CMC), and for an induced leakage of ionic detergents also below their CMCs. PMID- 24234095 TI - Analytical applications of reactors containing immobilized enzymes. AB - The theory for analytical packed-enzyme reactors is discussed and it is shown that a 100% conversion efficiency gives many advantages. This concept has been applied to methods for substrate determinations of urea, amino acids, and glucose. Enzyme reactors have also been used in the effluent from a Chromatographic column to enhance selectivity and sensitivity for cholesterol. Enzyme reactors for the determination of inhibitors, e.g. mercury ions, should be designed differently. A low conversion efficiency gives high sensitivity and a linear response. PMID- 24234094 TI - Immobilized enzymes as analytical reagents. AB - Immobilized enzymes are becoming increasingly popular as analytical reagents because of their reusability, stability, and sensitivity to many inhibitors that would seriously interfere in assays using soluble enzymes. In this article, some of the kinetic and catalytic effects of immobilized enzymes in analysis will be discussed. The shift of the activity-pH profile curves on immobilization, the changes in temperature dependence. the inhibitor constants (K1). Michaelis constants (K m ), and the maximum velocity (Vmax). plus others, will be discussed. Finally, the use of these immobilized enzymes in fluorometric and electrochemical monitoring systems will be shown, and the future of these reagents in various areas will be discussed. A survey of enzyme electrodes will be presented as an example of the use of immobilized enzymes. Application of immobilized enzyme technology to the assay of BUN, glucose, uric acid, amino acids, ethanol. and other metabolites will be discussed. PMID- 24234096 TI - Determination of phenol and catechol concentrations with oxygen probes coated with immobilized enzymes or immobilized cells. AB - The enzyme phenol 2-hydroxylase was immobilized on Sepharose and used in conjunction with an O2 electrode for quantitating phenol. Similarly, catechol 1,2 oxygenase was used for quantitating catechol. A third probe was prepared by immobilization ofTrichosporon cutaneum cells rather than purified phenol 2 hydroxylase for phenol quantitation. The whole cell system gave results comparable to the immobilized enzyme system. PMID- 24234097 TI - A glucose electrode for fermentation control. AB - An oxygen-stabilized enzyme electrode was applied to monitor the glucose concentration in a fermentor during a batch culture ofCandida utilis. The electrode contains an electrolysis circuit for generation of oxygen within the enzyme layer that keeps the oxygen activity in that layer at the same level as that of the surrounding broth. The electrolysis current is used as a measure of the glucose concentration in the broth.The glucose analysis continued without major disturbances when the dissolved oxygen pressure gradually decreased during the fermentation and also when the broth was subjected to a sudden increase in dissolved oxygen tension. The electrode could also be used in an anaerobic broth. Then the reference electrode was replaced by a constant reference potential that simulated a reference oxygen activity. PMID- 24234098 TI - Biospecific reversible immobilization : A method for introducing labile structures into analytical systems. AB - Immobilized lectins placed in continuous flow systems were used for biospecific reversible immobilization of labile biochemical structures, e.g., enzymes such as ascorbic acid oxidase and acetylcholine esterase, and cells, such as red blood cells and lymphocytes. The species thus immobilized were applied in continuous flow analytical processes. PMID- 24234099 TI - The enzyme thermistor. AB - This is a brief review of some applications and a description of the enzyme thermistor, which in effect is a flow-calorimeter designed for routine analysis in clinical chemistry, biochemistry, environmental control, and biotechnology. The heat produced in a small column filled with immobilized enzyme is measured with a thermistor, hence the name enzyme thermistor (1, 2). PMID- 24234100 TI - Use of hydrogen-sensitive Pd-MOS materials in biochemical analysis. AB - A metal oxide semiconductor sensitive to hydrogen was used to monitor H2 production from immobilizedClostridium acetobutylicum cells and from immobilized hydrogenase on a continuous basis. PMID- 24234101 TI - Enzyme thermistors for process monitoring and control. AB - In today's biotechnology there is an increasing demand for appropriate analytical systems for process control. At present the most widely used control systems are based on measurements of pH, pO2, and pCO2. Such systems do not allow the direct measurement of substrates and products. To overcome this drawback sensors such as enzyme thermistors and enzyme electrodes have been designed and their development into industrial useful sensors for monitoring and controlling is the subject of active research. PMID- 24234102 TI - Recent trends of biosensors in Japan. AB - Remarkable progress has been made in the development of bioelectrochemical sensors, and various kinds of biosensors have been developed and applied in analytical chemistry. Many of these enzyme, microbial, and immunosensors have been recently developed in Japan and in this paper, recent trends in Japanese biosensor development are described. PMID- 24234103 TI - Breaking the barriers to environmental information: Workshop rationale and organization. PMID- 24234104 TI - Environmental information - A step to knowledge and understanding : Opening comments. AB - At a time when information and knowledge about the environment and the economy are increasing, problems of both environment and economy are growing more serious. It is the role and opportunity of a university institute concerned with research on environment and economy to convert information about the environment into knowledge, and to explore applications of that knowledge in areas of economic management and policy. The main barriers to production and dissemination of information that can contribute to effective environmental knowledge are those that affect the reliability, adequacy, accessibility, and understandability of environmental information. Such barriers may be systematic, biasing the gathering of information and selecting in advance who may benefit from it; they may be barriers of translation, with distortion of content or significance; barriers of sophistication, that determine both content and context; or, most difficult in the environmental field, barriers imposed by problems of scale and relationships of different scales. To be useful, information cannot be purely objective, but must have subjective value added. There is a staircase of 'knowing', progressing from Observation and Measurement, to Data, to Information, to Knowledge, to Understanding, and finally to Wisdom, presenting increasing barriers of subjective value, interpretation, and integration at each step. PMID- 24234105 TI - Environmental science as a social process. AB - The felt need for better environmental information for planners and voters is based on maladaptive beliefs about the nature of knowledge and social order. Because there is not a meta-model which links the individual environmental sciences into a coherent whole, understanding complex environmental problems is necessarily a process of discourse between scientists from separate sciences-a process of gaining trust, building new patterns of thinking, and reaching toward new consensuses. By acknowledging the nature of the process, we can improve upon it and relieve the felt need for better environmental information. PMID- 24234107 TI - Scientific barriers : A commentary. PMID- 24234106 TI - New perspectives on sustainable development and barriers to relevant information. AB - Sustainable development may mean different things to people with different worldviews. We sketch four worldviews, drawing on a schema developed by Bryan Norton. Of these four worldviews, i.e. exploitist, utilitist, integrist and inherentist, the third is the most consistent with the Brundtland Report (WCED 1987) and the Great Lakes Water Quality Agreement (GLWQA 1987).The integrist perspective combines analytic reductionistic study with comparative contextual study, with emphasis on the latter. This integrative approach moves from over reliance on utilist information services such as impact assessment towards transactive study. Our own compromise emphasizes a stress-response approach to a partial understanding of complex cultural-natural interactions within ecosystems. Both cultural and natural attributes of ecosystems must be addressed.Currently the federal Canadian government tends toward an exploitist worldview; current government R&D funding and subsidies reflect this view. Old-fashioned scientists who rely on a monocular analytical vision of the world's minutiae may find contextual historical study offensive; these scientists hold sway on some advisory boards and hence research funding. Difficulty in finding funding for integrist information services should not be interpreted as a lack of need for this information; rather this difficulty results from resistance to a changing worldview. PMID- 24234108 TI - Scientific barriers : A commentary. PMID- 24234109 TI - Scientific barriers : A commentary. AB - Whatever the appeal of extreme integrism or holism, science is necessarily more utilist and partial. We can only address our environmental problems scientifically if we identify the most pressing and attack them first. To do so, we must break with the monistic ideals and traditions of both theoretical and mechanistic ecology to pursue particular solutions instead of global models. Statistical analysis of empirically identified patterns has proven effective in providing such solutions, perhaps because empirical patterns are less valueladen than theoretical or mechanistic alternatives or because such patterns are closer to experience and easier to understand. Unfortunately, such simple analyses are often less valued by leading ecologists who seek intellectual content rather than predictive power and practicality. To overcome this barrier to actionable information, the body of scientists must reaffirm their commitment to environmental action through their work as journal referees, grant reviewers, scientific critics and teachers. PMID- 24234110 TI - The seven deadly sins and the three poisons: A commentary on barriers to environmental information. PMID- 24234111 TI - Using technology to access regional environmental information. AB - Distinctions between holistic and presciptive technologies, and holistic and reductionist science are a backdrop to examination of two widespread environmental problems: eutrophication in the Bay of Quinte, Lake Ontario, and acidification of lakes in eastern Canada. Evidence is presented on a shift from prescriptive toward holistic approaches. Holistic solutions to technological limitations are discussed with emphasis on the interactive procedures people use to solve problems, rather than on the physical tools which are often employed in a prescriptive manner. Local gathering and integration of environmental information is presented as the key to macro-environmental assessments. Recommendations stress (i) the need for ecologists in every ecosystem, (ii) training with emphasis on problem-solving techniques, (iii) wide-spread use of microcomputers, a potent holistic technology, to transfer information and concepts, and (iv) local selection of indicators with the advice that they be simple and biotic. PMID- 24234113 TI - The role of geomatics in developing the environmental information infrastructure. PMID- 24234112 TI - Barriers to the use of remote sensing in providing environmental information. AB - Remote sensing from aircraft and earth-observing satellites is an essential source of environmental information and, at regional and global scales, remote sensing from satellites is often the only way in which some information can be collected. Naturally there are technical limitations, such as low resolution and the inability of optical sensors to see through clouds that restrict the use of satellite data, but technology is moving rapidly and major advances can be expected during the current decade, especially from radar satellites.The main barriers to the use of environmental information provided by remote sensing are not technological, but include cost and a need for training and transfer of technology, and a requirement for users to depart from traditional methods where new technology offers distinct advantages. Perhaps the most important contributions that users of remote sensing data can make to breaking down the barriers to the use of environmental data is to provide very clear statements of their information requirements so that technology can develop to meet these requirements. PMID- 24234114 TI - Technological barriers : A commentary. PMID- 24234115 TI - Technological barriers : A commentary. PMID- 24234117 TI - Technological barriers : A commentary. PMID- 24234116 TI - Technological barriers : A commentary. PMID- 24234118 TI - Technological barriers to environmental information : Chairperson's summary. PMID- 24234119 TI - Institutional barriers to environmental information. AB - Several barriers impede the free flow of environmental information in the government's hands to the public. The most important of these are the compartmentalization of environmental information among several departments, the manipulation of information to protect vested bureaucratic or political interests and, lastly, the withholding of information. The media's ineffective coverage of environmental issues and the small number of well-funded environmental groups constitute two additional institutional barriers to the broader dissemination of environmental information. Solutions proposed to reduce these barriers include the creation of an independent Commissioner on the environment reporting publicly to Parliament about the government's performance and the development of a widely available system of indicators to inform the public about changes in environmental quality. PMID- 24234120 TI - Institutional barriers: A synoptic or pluralist approach. PMID- 24234121 TI - Political, social and institutional barriers to environmental information : A commentary. PMID- 24234122 TI - Political, social and institutional barriers to environmental information : A commentary. PMID- 24234123 TI - Institutional, political and social barriers to environmental information : A summary and a comment. PMID- 24234124 TI - Environmental Information Systems (EIS) in third world countries: Barriers and opportunities. PMID- 24234125 TI - Women as critical users of environmental information. PMID- 24234126 TI - Panel 4: Opportunities in third world countries : A commentary. PMID- 24234127 TI - Panel 4: Opportunities in third world countries : A commentary. PMID- 24234128 TI - Panel 4: Opportunities in third world countries : A commentary. PMID- 24234129 TI - Opportunities in the third world : A summary and comment. PMID- 24234130 TI - Breaking the barriers to environmental information: Concluding remarks. PMID- 24234131 TI - Workshop sponsors. PMID- 24234133 TI - Cultural competency in genetic counseling. AB - Incorporating a cross-cultural curriculum into genetic counseling training programs demonstrates a professional conviction of genetic counselors that cultural issues are important in genetic counseling. Funded by the Special Projects Fund in 1993 from the National Society of Genetic Counselors and the Kitson Fund from the Department of Social, Organizational, and Counseling Psychology, Teachers College, Columbia University, theHandbook of Cross-Cultural Genetic Counseling was developed to provide genetic counseling programs a curriculum to teach cross-cultural genetic counseling. The theoretical rationale for the development of a cultural curriculum is presented. By expanding cultural knowledge, developing an awareness of oneself and others, and increasing the repertoire of culturally relevant counseling skills within a socio-political context, genetic counselors will be able to better serve all clients seeking genetic counseling. PMID- 24234134 TI - Education and testing strategy for large-scale cystic fibrosis carrier screening. AB - Population-based screening for cystic fibrosis carrier mutations presents a number of challenges for genetic counselors, owing primarily to the inability of current DNA testing technology to identify all possible mutations and the difficulty involved in conveying the concept of residual risk to those patients who test negative. To address these issues, we are conducting a pilot study, as part of a consortium established by the National Center for Human Genome Research, to explore the efficacy, acceptance, and psychosocial impact of various approaches to carrier screening in an ethnically diverse Southern California population. This article reports the patient instructional and screening strategies we developed in the initial phase of the project in order to optimize our chances of answering these questions and delivering this service on a large scale. PMID- 24234135 TI - Abstracts of papers presented at the Thirteenth Annual Education Conference : 25 years of genetic counseling ... Expanding roles, extending horizons. PMID- 24234136 TI - Niflings are nephews and nieces. PMID- 24234137 TI - Living with patients' decisions. PMID- 24234138 TI - Foreword by Klaus Topfer German Federal Minister of Environmental Affairs : For the first issue of the international journal "Environmental Science and Pollution Research". PMID- 24234139 TI - Editorial by Otto Hutzinger Editor-in-Chief. PMID- 24234140 TI - Haloacetic acids, phytotoxic secondary air pollutants. AB - Haloacetic acids are atmospheric oxidation products of airborne C2-halocarbons which are important solvents and propellants. Levels of trichloroacetate (TCA) in conifer needles from mountain ranges in Germany (Black Forest, Erzgebirge) and from two sites in Finland are compared; TCA is present in conifer needles at concentrations up to 0.7 MUmol/kg, MCA up to 0.2 MUmol/kg. At the Finnish sites, TCA-concentrations and branch degeneration symptoms of Scots pine are correlated. Monochloroacetate (MCA) has been determined in needle samples from Southern Germany in concentrations exceeding its phytotoxicity threshold towards photoautotrophic organisms. Data on atmospheric chloroacetate levels in Germany are also given; ambient air levels of chloroacetic acids range from about 2 pmol/m(3) (TCA) to 390 pmol/m(3) (MCA). TCA and dichloroacetic acid (DCA) arise from atmospheric oxidation of airborne C2-chlorocarbons, while the source of MCA is not yet known; several tentative pathways are suggested. PMID- 24234141 TI - Textiles as a source of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in human skin and sewage sludge. AB - Polychlorinated dibenzo-p-dioxins and dibenzofurans were measured in low- to high ppb concentrations in several pieces of new clothing from different manufacturers. It was shown that these contaminants are transferred from textiles to human skin during wearing. They were also present in shower water and were washed out of textiles during washing. Extensive evidence was found indicating that contaminated textiles are a major source of chlorinated dioxins and furans in non-industrial sewage sludge, dry cleaning residues and house dust. PMID- 24234142 TI - Upcoming canadian environmental meetings. PMID- 24234143 TI - Sorption kinetics of chlorinated hydrophobie organic chemicals : Part I: The Use Of First-Order Kinetic Multi-Compartment Models. AB - This is the first of a two-part series describing the Sorption kinetics of hydrophobic organic chemicals. This paper discusses the use of first-order kinetic compartment models in environmental studies, of subjects such as bioaccumulation and sorption. A comprehensive mathematical description and model calculations are presented. Differences between these models and the pharmacokinetic compartment models will be indicated, emphasis being given to the use of the former in sorption studies. PMID- 24234145 TI - Database ABIOTIKx- Assessment of the chemical life of organic substances in the troposphere. PMID- 24234144 TI - Dietary and environmental estrogens and antiestrogens and their possible role in human disease. AB - Recent reports have suggested that dietary and environmental estrogens such as organochlorine pollutants may play a role in the increased incidence of breast cancer in women and disorders of the male reproductive tract. For example, elevated levels of DDE and polychlorinated biphenyls (PCB) have been measured in women with breast cancer. However, it should also be noted that numerous environmental and dietary compounds have also been characterized as antiestrogenic and as inhibitors of mammary cancer cell growthin vitro and/orin vivo. Some of these compounds include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, polynuclear aromatic hydrocarbons (PAH), other naturally occurring TCDD receptor agonists, retinoids, phorbol esters, terpenes, fatty acids, and polysaccharides. Thus, it is possible that dietary and environmental estrogens and antiestrogens may be contra-active, and these interactions must be considered in the overall risk assessment of the potential adverse human and environmental health impacts of these chemicals. PMID- 24234146 TI - Adsorption of organic vapors on polar surfaces- Recent advances. AB - This paper summarizes recent research on the adsorption of organic vapors on surfaces. Since the low gas phase concentration range is typical for environmental situations, this review is restricted to these adsorption coefficients.Two environmental parameters have a strong influence on the adsorption of organic vapors on polar surfaces:temperature andrelative humidity (which is the most suitable parameter for describing the influence of ambient moisture). An exponential relationship was found for the adsorption coefficientversus relative humidity and the reciprocal temperature, respectively. Comparing the heats of adsorption, two different groups of substances emerged: polar chemicals exhibited heats of sorption which were higher than their corresponding heats of condensation due to their ability to form hydrogen bonds, while for the nonpolar compounds the opposite was true. Sorption takes place on the surface of an adsorbed water film when the relative humidity exceeds the value which is necessary to form a monomolecular layer of water on the surface of the adsorbent (>= 30 % relative humidity). Therefore, at temperature below 0 degrees C, a change in the adsorption behavior might be expected due to a change of properties of the adsorbed water film. However, no alterations were observed at temperatures from -12 degrees C to + 4 degrees C (adsorption on quartz sand). The results were comparable to those at much higher temperatures (50 - 80 degrees C).A statistical approach for the prediction of the adsorption coefficients from physico-chemical parameters of the substances (vapor pressure, polarizability, and electron-donating capability) was developed and good agreement was found with experimental results and independent data from the literature. Finally, two special cases, the adsorption on bulk water and ice, are discussed. PMID- 24234147 TI - Two years of oil disaster in the Arabian Gulf. AB - In January-February 1991, about 1 million m(3) of crude oil were released into the Arabian Gulf as a means of ecological warfare. A stretch of 644 km along the Saudi Arabian coast was heavily polluted over a width between a few meters and more than one kilometer. In four studies performed between March 1991 and April 1993 the state of representative areas of the affected coast was examined with the result that only minor changes were found in those oiled zones which are seldom inundated by the tides. Technical measures up to 1993 did not exceed the test level. A biological regeneration process is in progress which was not recognized as such in analyses of previous coastal oil pollution. Cyanobacterial mats, containing hydrocarbon-degrading bacteria, grow on oiled sediments which are regularly reached by tidal water. Shrinking and fracturing of the stable tar crusts starts a process of loosening and degrading of aged hydrocarbons. PMID- 24234148 TI - Environmental hazard : Assessment of chemicals and products Part I: General assessment principles. PMID- 24234149 TI - Development of Life Cycle Assessment (LCA) : The role of SETAC (Society of Environmental Toxicology and Chemistry) and the 'Code of Practice'. PMID- 24234150 TI - Guidelines for Life-Cycle Assessment: : A 'Code of Practice' from the workshop held at Sesimbra, Portugal, 31 March - 3 April 1993 Society of Environmental Toxicology and Chemistry (SETAC). PMID- 24234151 TI - Analytical chemistry in Europe and international tendencies : The accreditation of analytical laboratories- Quality assurance in analytical chemistry. PMID- 24234152 TI - Dioxin '93- 13th international symposium on chlorinated dioxins and related compounds vienna, austria, september 20-24, 1993. PMID- 24234154 TI - Plumbagin, a vitamin K3 analogue, abrogates lipopolysaccharide-induced oxidative stress, inflammation and endotoxic shock via NF-kappaB suppression. AB - Plumbagin has been reported to modulate cellular redox status and suppress NF kappaB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-alpha, IL-6 and prostaglandin-E2 production in a concentration dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-kappaB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-kappaB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin. PMID- 24234156 TI - The implementation and effects of Great Britain's National Lottery. AB - This article reviews the implementation of the British National Lottery since the first draw took place in November 1994. It seeks to analyse the experience to date against the background of the concerns expressed prior to its introduction and of the regulatory objectives set by the framework legislation. It also considers the impact that the Lottery is having upon the formulation and implementation of regulatory policy affecting other gambling media. The six sections following the introduction deal in turn with the Lottery's income, permitted games, the participants, the good causes benefiting from its proceeds, its impact on other gambling media, and its place within British government policy concerning the regulation of commercial gambling. PMID- 24234155 TI - Il1-beta involvement in cognitive impairment after sepsis. AB - Sepsis is defined as the host's reaction to infection and characterised by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, an imbalance of neurotransmitters, apoptosis and cognitive impairment. It's known that the IL-1beta is one of the first cytokines to be altered. Thus, the objective of this study was to evaluate the role of IL-1beta in cognitive parameters in brain tissue through the use of an IL-1beta (IL-1ra) receptor antagonist up to 10 days and to assess blood-brain barrier permeability, cytokine levels, oxidative parameters and energetic metabolism up to 24 h, after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation (CLP) procedure. Immediately after, the animals received one dose of 10 MUg of IL-1ra. After 24 h, the rats were killed and were evaluated for biochemical parameters in the pre-frontal cortex, hippocampus and striatum. After 10 days, the animals were submitted to the habituation to the open field and step-down inhibitory avoidance task. We observed that the use of IL-1ra reverted the increase of blood-brain barrier permeability in the pre-frontal cortex, hippocampus and striatum; the increase of IL-1beta, IL1-6 and TNF-alpha levels in the pre-frontal cortex and striatum; the decrease of complex I activity in the pre-frontal, hippocampus and striatum; the increase of oxidative parameters in pre-frontal cortex, hippocampus and striatum; and cognitive impairment. In conclusion, the results observed in this study reinforce the role of acute brain inflammatory response, in particular, the IL1beta response, in the cognitive impairment associated with sepsis. PMID- 24234157 TI - The relationship between gambling and video-game playing behavior in children and adolescents. AB - It is suggested that commercial video-games (e.g.Nintendo &Sega) and gambling activities have similar attractive features and intermittent reinforcement schedules. This research seeks to examine the nature of this relationship amongst children. One hundred and four children aged 9 to 14, from grades 4, 6, and 8, participated. A questionnaire exploring issues related to video-game playing and gambling behavior in children and adolescents was completed and a computerized blackjack game was individually administered. High frequency video-game players were compared to low frequency video-game players with respect to their gambling performance on the blackjack gambling task as well as on information gathered from the questionnaire. Of particular concern is the risk-taking strategies used by avid video-game players, whether or not children perceive gambling and video games as involving similar amounts of skill or whether they realize that gambling is primarily a game of chance. The findings, in general, suggest that high frequency video-game players gamble more than low frequency video-game players, report that gambling makes them feel more important, and take greater risks on the blackjack gambling task although no overall differences in success were found. Males exhibited greater risk-taking tendencies on the blackjack task than females. The clinical implications of the findings are addressed. PMID- 24234158 TI - Pathological gambling: Etiologic considerations and treatment efficacy of eye movement desensitization/reprocessing. AB - This study of 22 subjects who meet DSM IV criteria for Pathological Gambling (PG) tests a theory that the development of PG lies in the existence of unresolved trauma-related anxiety, similar to Post Traumatic Stress Disorder, and predicts that reduction of that anxiety will result in reduced pathological gambling behavior. The study compares the effect on gambling event frequency of Eye Movement Desensitization and Reprocessing (EMDR) therapy with cognitive therapy to that of cognitive therapy alone for subjects with and without reported trauma history. Results are significant for pre- vs post-EMDR (p =.04), for those with reported trauma history, (p=.01) and when controlled for frequency of sessions and time in therapy prior to the treatment (p=.04). Findings support an anxiety based model for the etiology of PG behavior. PMID- 24234159 TI - Skill versus luck: A motivational analysis of gambling involvement. AB - The purpose of the present investigation was to test the skill/luck distinction among gambling games by comparing the motivations underlying participation in a skill (horse racing) and a luck (lottery) betting activity. Predictions were made using Self-Determination Theory (Deci & Ryan, 1985, 1991). It was predicted that self-determined motivations (intrinsic motivation and identified regulation) would be more prominent for the skill game because it is conducive to optimal challenges, fun, and self-involvement. Conversely, the non self-determined forms of motivation (especially external regulation) should be more important for the game of luck because the luck dimension precludes true involvement of the self and orients the individual towards material gains. Results from a hierarchical discriminant function analysis, with 120 gamblers predominantly involved in one of the two betting activities, supported these hypotheses. These results highlight the relevance of a motivational analysis for a better understanding of the inherent properties of gambling games. PMID- 24234160 TI - Potential and probable pathological gamblers: Where do the differences lie? AB - A large proportion of adolescents engage in gambling activities and the prevalence of pathological gambling is high. This study presents a factor analysis of responses from 122 college students who obtained a score of 3 or greater on the South Oaks Gambling Screen (SOGS), the most widely used instrument to identify probable and potential pathological gamblers. The analysis showed five dimensions: Illegal Behaviors, Heavy Gambling, Eating Disorders, Parentally Modelled/Less Impulsive, and Worry. Analyses revealed that except for the Eating Disorders factor, all factors clearly differentiated the probable from potential pathological gamblers, as identified by the SOGS. Results raise important questions about the relationship of pathological gambling to other psychopathological or antisocial behaviors. Thus the probable pathological gambler category represents a wide-ranging behavioral profile that goes beyond gambling per se. Avenues for future research as well as clinical implications are discussed. PMID- 24234161 TI - Pathological gamblers in methadone treatment: A comparison between men and women. AB - This article uses data from interviews with 462 individuals enrolled in methadone treatment programs in New York City to compare the gambling and gambling-related drug use and criminal activities of those males (N=72) and females (N=27) found to be pathological gamblers. Both the male and female pathological gamblers were and continue to be actively involved in various forms of gambling. A greater proportion of males had engaged in almost all specific types of gambling, although differences between males and females were not all statistically significant. Males and females were very similar in terms of their patterns of drug and alcohol use and the substances they used when gambling. Males and females shared some reasons but also had separate reasons as to why they used heroin when they gambled. Males especially may participate in a variety of criminal and hustling activities to have the money to be able to gamble or to pay gambling debts. The implications of this research are discussed. PMID- 24234162 TI - Video lottery gambling: Effects on pathological gamblers seeking treatment in South Dakota. AB - Fifty-eight pathological gamblers receiving treatment for addictive illness in two South Dakota hospitals were assessed for types of gambling and grouped into three categories; 15 "video lottery only" (VLO), 36 "video lottery mixed" (VLM), and 7 "not video lottery" (NVL). There were 51 male and 7 female respondents, with a mean age of 38.2. We hypothesized that video lottery would be the predominant type of gambling on several dimensions: level of recent activity, most money lost on one occasion, and number of DSM-IV criteria met. Of all gamblers, 87.9% had pathological involvement with video lottery. Video lottery gambling accounted for the highest level of recent activity. In the VLM group, video lottery gambling led to greater single-occasion monetary losses. In addition, significantly more DSM-IV criteria were met in the VLM group for video lottery gambling than for other forms of gambling these subjects had engaged in. Results indicate that video lottery gambling is the predominant type of gambling behavior engaged in by gamblers seeking treatment for addictive illness in South Dakota. We propose that these findings could be associated with the availability and stimulus differences between video lottery and other gambling types. PMID- 24234163 TI - Understanding the means and objects of addiction: Technology, the internet, and gambling. AB - This article describes how using new computer technology and the Internet for gambling can represent both the means and object of addiction. However, these technological factors do not represent the cause of addictive behavior. Given the widespread availability of computer technology and the remarkable expansion of the Internet, it is not surprising, however, that these technological advances have become associated with intemperate gambling activities. By discussing the concept of addiction and its associated social setting, neurochemistry, and gaming characteristics, this article suggests that addiction is the result of shifts in subjective experience and that new technology and the Internet can provide relatively reliable and potent contemporary vehicles for changing emotional states. PMID- 24234164 TI - Gambling on the internet: A brief note. PMID- 24234165 TI - Erratum. PMID- 24234166 TI - Online friends, offline loved ones, and full-time media: young adult "mass personal" use of communication resources for informational and emotional support. AB - As Web 2.0 technologies proliferate, patient education is changing dramatically. Information about prevention and survivorship arrives from a mix of sources. The present manuscript describes a study to shed light on how young adults (YAs) affected by cancer manage the digital world. Our investigation was guided by a research question asking how young adults affected by cancer engage in communication work in an environment of mass personal communication. The sample for this research consisted of 500 posts comprising 50 complete threads from an online support community for young adults affected by cancer. Threads were purposively sampled in a multi-stage process. Researchers used constant comparison to define themes, examining text in increments. Individuals harnessed assets of various communication tools for the purposes of message preparation and credibility checking. YAs demonstrated the multi-channel way they move between channels for different purposes, driven by preparation for future interactions. The result is a process that allows co-creation of knowledge in a trusted community. Findings indicate that completing communication work through multiple channels in a deliberate and savvy way is normal for YAs, particularly for message preparation and credibility checking. The multidirectional nature of digital tools plays an important role for YAs, as interactive resources appear to be the first or second stop for information after key events in the cancer trajectory. Results from this study are important as guidance to help manage the volume and depth of information common to the cancer experience in the Web 2.0 world. PMID- 24234167 TI - Tolerance for inconsistency in foreign-accented speech. AB - Are listeners able to adapt to a foreign-accented speaker who has, as is often the case, an inconsistent accent? Two groups of native Dutch listeners participated in a cross-modal priming experiment, either in a consistent-accent condition (German-accented items only) or in an inconsistent-accent condition (German-accented and nativelike pronunciations intermixed). The experimental words were identical for both groups (words with vowel substitutions characteristic of German-accented speech); additional contextual words differed in accentedness (German-accented or nativelike words). All items were spoken by the same speaker: a German native who could produce the accented forms but could also pass for a Dutch native speaker. Listeners in the consistent-accent group were able to adapt quickly to the speaker (i.e., showed facilitatory priming for words with vocalic substitutions). Listeners in the inconsistent-accent condition showed adaptation to words with vocalic substitutions only in the second half of the experiment. These results indicate that adaptation to foreign-accented speech is rapid. Accent inconsistency slows listeners down initially, but a short period of additional exposure is enough for them to adapt to the speaker. Listeners can therefore tolerate inconsistency in foreign-accented speech. PMID- 24234169 TI - On the apparent persistence of disparlure in the human body. PMID- 24234168 TI - The resilience of object predictions: early recognition across viewpoints and exemplars. AB - Recognition of everyday objects can be facilitated by top-down predictions. We have proposed that these predictions are derived from rudimentary image information, or gist, extracted rapidly from the low spatial frequencies (LSFs) (Bar Journal of Cognitive Neuroscience 15: 600-609, 2003). Because of the coarse nature of LSF representations, we hypothesized here that such predictions can accommodate changes in viewpoint as well as facilitate the recognition of visually similar objects. In a repetition-priming task, we indeed observed significant facilitation of target recognition that was primed by LSF objects across moderate viewpoint changes, as well as across visually similar exemplars. These results suggest that the LSF representations are specific enough to activate accurate predictions, yet flexible enough to overcome small changes in visual appearance. Such gist representations facilitate object recognition by accommodating changes in visual appearance due to viewing conditions, and help generalize from familiar to novel exemplars. PMID- 24234170 TI - Foliage constituents of douglas fir (Pseudotsuga menziesii (Mirb.) Franco (Pinaceae)): Their seasonal variation and potential role in douglas fir resistance and silviculture management. AB - Seasonal changes in the production of primary nutrients (soluble carbohydrates) and secondary metabolites (terpenes, monomeric phenolics, and tannins) in the current needle tissue of Douglas fir were investigated. All four classes of compounds showed significant seasonal changes in concentration during foliage development. Most terpenes increased significantly in concentration from June 11 to August 3, and then showed declining concentrations to September 20. The most dramatic and significant seasonal increases occurred inalpha-pinene, camphene, and bornyl acetate concentrations. The monomeric phenolics chlorogenic acid, taxifolin glucoside, quercetin galactoside, and those unknown phenolics showed an overall trend of declining in concentration from June 11 through September 20. However, considerable variation between sampling dates in the concentration of these phenolics was noted. Tannin concentration decreased significantly from June 11 to July 9, and then increased in concentration to the September 20 sampling date. Fructose, galactose, glucose, and sucrose tended to decrease from June 11 to September 20. However, significant variation between sampling dates was evident in these compounds as well. Galactose was the major compound in the soluble carbohydrate fraction, amounting to almost 80% of the total concentration throughout the growing season. These data suggest that if phenolics and tannins function as defenses, they would only affect second- and possibly third-instar budworm larvae during the time that these instars mine the buds. Camphene,alpha pinene, and bornyl acetate increased in concentration throughout the growing season and may be effective deterrents to the budworm. Both bornyl acetate and camphene have been shown in field and laboratory studies to increase larval mortality and adversely affect budworm larval growth. Carbohydrates generally act as nutrients that enhance herbivore growth. However, in a previous study, galactose was found to cause reduced budworm larval growth and increased larval mortality. PMID- 24234171 TI - Spined citrus bugs,Biprorulus bibax breddin (Hemiptera: Pentatomidae), do not discriminate between enantiomers in their aggregation pheromone. AB - Female spined citrus bugs,Biprorulus bibax, in outdoor flight cage tests did not discriminate between synthetic aggregation pheromone blends containing either the racemate, natural (3R, 4S)-(-) or unnatural (4S, 3S)-(+) enantiomers of the major hemiacetal component (3R, 4S, 1'E)-3,4-bis(1'-butenyl)tetrahydro-2-furanol. Two to three times as many bugs were attracted to pheromone-baited sites compared to unbaited sites. The racemate of the hemiacetal is easier and less costly to synthesize than the enantiomers and will be used in development of the pheromone as a management tool for this pest. PMID- 24234172 TI - Olfactory responses of the parasitoidDiaeretiella rapae (Hymenoptera: Aphidiidae) to odor of plants, aphids, and plant-aphid complexes. AB - Diaeretiella rapae (M'Intosh) (Hymenoptera: Aphidiidae) is a parasitoid of several aphid species, including the Russian wheat aphid (RWA),Diuraphis noxia (Mordvilko), and the cabbage aphid (CA).Brevicoryne brassicae (L.). The response of matedD. rapae females to odors from wheat, cabbage, and plant-host complexes was investigated using a four-choice olfactometer. Experienced parasitoids, but not inexperienced females, responded positively to odors of the wheat-RWA complex in a no-choice test. In choice tests, experienced parasitoids did not respond to odors of uninfested cabbage and wheat leaves, but did respond positively to aphid infested plants and to aphids alone. The response ofD. rapae to the cabbage-CA complex and to CA alone was significantly greater than to the wheat-RWA complex and RWA alone, suggesting an innate odor preference for crucifer-feeding aphids. PMID- 24234173 TI - Antimicrobial activity of dogwood fruits (Cornus drummondii) from winter food caches of eastern woodrats (Neotoma floridana). AB - Post-harvest loss of resources to microbial competitors affects a number of species of animals, and many of them have evolved behaviors that reduce the likelihood of such loss. We previously described the inhibition ofBacillus psychrophilus by dogwood fruits (Cornus drummondii), which can comprise a significant portion of the winter food cache of the eastern woodrat (Neotoma floridana). The present study is a further investigation of the ability of dogwood fruits to inhibit growth ofB. psychrophilus. Additionally, we tested the antimicrobial activity of dogwood fruits onEscherichia coli andStaphlococcus aureus. Results of our study indicate that fresh fruits inhibit the growth ofB. psychrophilus andS. aureus but notE. coli. However, fruits taken from woodrat dens after four and six months storage inhibited growth of all three species of bacteria. Further, the strength of inhibition increased over the test period. We suggest the presence of an inhibitor allows woodrats to compete effectively for a valuable and limited food resource. PMID- 24234174 TI - A critical body size for use of pheromones in mate location. AB - Pheromones have demonstrated importance in mate location in many insect species. Because chemoreception is the most universal sense, it has been assumed that pheromones also are important in aquatic organisms, including bacteria, but few have been found. The physical limits on effective strategies for organisms to come into contact for mating were modeled with assumptions appropriate for organisms less than a millimeter in size in an open aquatic environment. One sex was assumed to be motile, while the other sex was passive or devoted energy to locomotion or to diffusible pheromone production. Assuming spherical organisms, random locomotion by the second sex at the same velocity as the first sex increases the chances of contact by a factor of 4/3 over being passive; this ratio is independent of size. For detection by contact, the effectiveness of searching increases with the third power of the radius of the organisms; for detection by pheromones, search effectiveness increases with the seventh power of the radius above a critical size. Diverting energy from motility to pheromone production is not productive for organisms smaller than the critical size, which corresponds to a radius of 1.8 times the square root of the diffusion coefficient of the pheromone times the threshold concentration for detection divided by the rate of pheromone production per unit volume of organism. Thus, pheromone production is very favorable for organisms much above the critical size, which appears to be between 0.2 and 5 mm in water. On the other hand, bacteria are probably too small to use diffusable pheromones for mate location; most protozoans and rotifers may also be too small. PMID- 24234175 TI - Metabolism of 1,8-cineole in tea tree (Melaleuca alternifolia andM. linariifolia) by pyrgo beetle (Paropsisterna tigrina). AB - The frass of the pyrgo beetle (Paropsisterna tigrina) feeding on commercial plantations of the terpinen-4-ol chemical variety of the Australian tea tree.Melaleuca alternifolia, was found to contain a volatile oil almost identical to the essential oil of the ingested leaf. When beetles were fed leaf containing substantial quantities of 1,8-cineole, the predominant frass metabolite as determined by MS, IR,(13)C and(1)H NMR, GC, and CoGC was (+)-2beta hydroxycineole. Both male and female adults and larvae metabolizedMelaleuca oils in similar ways. PMID- 24234176 TI - Antitermitic activity ofLonchocarpus castilloi flavonoids and heartwood extracts. AB - The heartwood of the tropical treeLonchocarpus castilloi Standley (Leguminosae) is highly resistant to attack by the drywood termitesCryptotermes brevis (Walker); nevertheless successive extraction with hexane, diethyl ether, acetone, methanol, and water reduced its resistance to these organisms. Antitermitic properties of the extracts were bioassayed using impregnated filter paper disks. Although the five extracts reduced both feeding and survival ofC. brevis, no significant differences among them were detected. Choice feeding tests showed that termites avoided eating the paper treated with the extracts. Two flavonoid compounds isolated from the heartwood, castillen D and castillen E, impregnated into filter paper showed concentration-dependent feeding deterrent activity, but were not toxic toC. brevis. PMID- 24234177 TI - Rejection of host plant by larvae of cabbage butterfly: Diet-dependent sensitivity to an antifeedant. AB - Garden nasturtium,Tropaeolum majus (Tropaeolaceae), is an acceptable host plant for the cabbage butterfly,Pieris rapae. Eggs are readily laid on the plant and hatching larvae feed and develop into normal pupae and adults. However, when second- to fifth-instar larvae were transferred from cabbage to nasturtium, they refused to feed and starved to death. Similar results were obtained when larvae were transferred from other host plants to nasturtium. However, larvae that were reared on nasturtium readily accepted cabbage as a new host plant. We have demonstrated the presence of strong antifeedants in nasturtium foliage and identified the most prominent active compound as chlorogenic acid. However, larvae reared on nasturtium had limited sensitivity, and larvae reared on a wheat germ diet were completely insensitive to the antifeedants. Larvae apparently develop sensitivity to the deterrent as a result of feeding on other host plants, whereas continuous exposure to the deterrent causes habituation or suppression of sensitivity development. The results demonstrate that dietary experience can dramatically affect the response of an insect to a potentially antifeedant compound in a plant. PMID- 24234178 TI - Evolution and function of lingual shape in lizards, with emphasis on elongation, extensibility, and chemical sampling. AB - Major squamate taxa exhibit extreme variation in lingual morphology, presumably due to correlated variation in trophic and chemosensory functions. Data are presented on evolution of lingual shape documenting several trends: (1) Resting lingual elongation is greatest in families specialized for lingual chemosensory sampling. (2) The greatest increase in elongation achievable by intralingual means including elasticity and foretongue retractility occurs in families with intermediate degrees of lingual specialization for chemosensory sampling. Sampling efficiency may be enhanced by the ability to extend the tongue well beyond the mouth, with resting elongation and intralingual extensibility perhaps jointly determining distance extended. In families lacking sufficient resting elongation, augmentation of intralingual extensibility may be a means of approaching optimal protrusion distances. Decreased extensibility evolved in tandem with the greatest resting elongation, suggesting that resting elongation may be more efficient for protrusion and that elasticity declines as optimal resting length is approached. The optimal shape for chemosensory sampling may be predicted to be highly elongate, as in teiids, varanids, and colubrids. The tongue should be broad at the tip for prehension (as in iguanians), fleshy for manipulation and swallowing, and broad at the base for tamping prey into the esophagus. (3) Lingual surface area relative to that of a rectangle of dimensions length * base width varies accordingly. Relative area is high in families that do not tongue-flick much while foraging because tongues are broad and fleshy throughout their length. It is low in families that have wedge-shaped tongues and intermediate specialization for chemosensory sampling. Narrowing of the anterior tongue may improve chemical sampling. Relative lingual area in chemosensory specialists is very high, with progressive narrowing toward the base as optimal sampling shape is approached in taxa lacking lingual function in swallowing, prehension or prey manipulation. PMID- 24234179 TI - Hugh Esmor Huxley (1924-2013). PMID- 24234180 TI - Microwave ablation of lung tumours: single-centre preliminary experience. AB - PURPOSE: This study was done to evaluate the feasibility, effectiveness and safety of microwave (MW) ablation of lung tumours. MATERIALS AND METHODS: Twenty four patients underwent percutaneous MW ablation of 26 intraparenchymal pulmonary masses. All patients were judged to be inoperable on the basis of tumour stage, comorbidities, advanced age and/or refusal to undergo surgery. Ablation was performed using a microwave generator (Evident Microwave Ablation System, Covidien Ltd., Dublin). Lesions with a diameter <= 3 cm were treated with a single antenna, lesions with a diameter >3 cm were treated by positioning two or more antennae, simultaneously. All patients underwent computed tomography (CT) follow-up with and without contrast administration at 1, 3 and 6 months and then yearly in combination with complete blood and metabolic tests. RESULTS: Technical success was 100 %. No major complications were recorded. Asymptomatic grade-1 pneumothorax was recorded in 9 patients (37.5 %). One case of asymptomatic pleural effusion and one of haemoptysis, not requiring transfusion, were observed. No patients were diagnosed with a post-ablation syndrome. Complete necrosis was observed in 16 of 26 lesions (61.6 %). Partial necrosis was obtained in 30.8 % (8/26 lesions); in one case (3.8 %) a progression of the disease was recorded and in another case (3.8 %) a stability was observed. CONCLUSIONS: Our preliminary experience may be considered in accordance with literature dates, in terms of efficacy and safety. PMID- 24234181 TI - Assessment of 64-row computed tomographic angiography for diagnosis and pretreatment planning in pulmonary sequestration. AB - PURPOSE: This study was done to evaluate the clinical implications and results of a prospective protocol using 64-row computed tomographic angiography (CTA) for diagnosis and pre-treatment planning in pulmonary sequestration (PS). MATERIALS AND METHODS: Forty-five patients with suspected PS were referred for CTA examination. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of measures used to detect PS were determined by patient-based and aberrant systemic artery-based evaluations. The location, the size and the number of aberrant systemic arteries, and the feasibility of endovascular treatment were analysed. The capability of CTA to provide a working view and the accuracy of measurements in choosing a coil were also assessed. RESULTS: Digital subtraction angiography and/or surgery revealed PS in 38 patients, and 7 patients had no PS. The patient-based evaluation yielded an accuracy of 97.8 %, sensitivity of 97.4 %, specificity of 100 %, PPV of 100 % and NPV of 87.5 %, in the detection of PS. CTA clearly depicted the PS in all 38 patients, and the aberrant systemic artery was accurately demonstrated in 37 out of 38 patients where endovascular treatment was possible. Working views for endovascular treatment were found in all patients with PS, and the choice of coil was correct in 37 out of 38 patients using CTA. CONCLUSIONS: 64-row CTA appears to be effective in terms of supporting accurate diagnosis and pre-treatment planning in PS. CTA is not only able to provide clear visualisation of aberrant systemic arteries but also provides detailed images of abnormal lung parenchyma and the airways. PMID- 24234182 TI - Rare causes of pulmonary hypertension: spectrum of radiological findings and review of the literature. AB - Following a brief introduction covering the clinical signs and symptoms of pulmonary hypertension (PH), its most recent classification into six groups, and the computed tomography (CT) features common to all forms of PH, this paper illustrates the typical patterns that can be found on chest radiography and CT in rare causes of PH. We present and compare with the existing literature our personal series of cases of rare forms of PH, found in the following diseases: veno-occlusive disease, pulmonary capillary haemangiomatosis, non-thrombotic pulmonary embolism (tumour embolism and carcinomatous lymphangitis, talcosis, hydatid disease), pulmonary artery sarcoma, neurofibromatosis, sarcoidosis, and Langerhans cell histiocytosis. Rare forms of PH show low incidence and prevalence, and are, therefore, poorly recognised. Their diagnosis is a challenge for clinicians, pathologists, and radiologists, and any additional knowledge about the CT findings may help the diagnosis in the case of patients affected by PH of unknown origin. PMID- 24234183 TI - Current clinical use of 18FDG-PET/CT in patients with thoracic and systemic sarcoidosis. AB - PURPOSE: This study assessed the role of whole-body (18)fluorodeoxyglucose positron-emission tomography/computed tomography ((18)FDG PET/CT) in the restaging and follow-up of patients with sarcoidosis previously studied by multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study enrolled 21 patients to evaluate the sensitivity, specificity and accuracy of (18)FDG-PET/CT and MDCT. The results of the two techniques were compared with the Mc Nemar test. Cohen's K was used to compare concordance at the different lesion sites. RESULTS: The sensitivity, specificity and accuracy of (18)FDG-PET/CT were 80, 66.67, and 76.19 %, respectively. The sensitivity, specificity and accuracy of MDCT were 93.33, 33.33, and 76.19 %, respectively. In 16 patients who underwent whole-body MDCT, the sensitivity, specificity and accuracy values were 91.67, 81.25, and 50 % (MDCT) and 100, 50, and 87.5 % ((18)FDG-PET/CT). CONCLUSIONS: (18)FDG-PET/CT is useful in evaluating the extent of sarcoidosis and recognising lesions at different sites, including lymph nodes, lungs, liver, spleen and bone. It also improves the interpretation of the morphological lesions seen on MDCT and depicts a larger number of lesions. Therefore, (18)FDG-PET/CT could be used to complement other more traditional techniques for the restaging and follow-up in patients with sarcoidosis. PMID- 24234184 TI - Impact of a breathing-control system on target margins and normal-tissue sparing in the treatment of lung cancer: experience at the radiotherapy unit of Florence University. AB - PURPOSE: In lung cancer, a high radiation dose to the target area correlates with better local control but is frequently counterbalanced by a higher risk of lung toxicity. Several methods exist to coordinate respiratory motion in lung radiotherapy. We aimed to investigate the impact of a breathing-control system on irradiated volumes and dosimetric parameters in three-dimensional conformal radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) treatments. MATERIALS AND METHODS: Twelve patients were scheduled for radical radiotherapy: five for SRT and seven for 3D-CRT. For each patient, in addition to the free-breathing computed tomography (CT) scan, four additional sets of CT slices were acquired using the Active Breathing Coordinator device (ABC, Elekta Oncology Systems Ltd., UK). RESULTS: The volumes acquired with the ABC device were significantly smaller than the free-breathing volumes [23 % reduction of planning tumour volume (PTV), p = 0.002]. ABC allowed a reduction of all dosimetric parameters [2.28 % reduction of percentage volume of lung treated to a dose of >= 20 Gy (V20), p = 0.004; 10 % reduction of mean lung dose (MLD), p = 0.009]. Significant differences were found both in SRT and in 3D-CRT, in peripheral and apical lesions. CONCLUSION: In our experience, ABC has the potential to reduce lung toxicity in the treatment of lung cancer; alternatively, it can allow the prescribed dose to be increased while maintaining the same risk of lung toxicity. PMID- 24234185 TI - Radiofrequency ablation of thoracic tumours: lessons learned with ablation of 100 lesions. AB - PURPOSE: Our aim was to analyse the results of our first 100 radiofrequency ablation (RFA) procedures, of primary (nonsmall-cell lung cancers, NSCLC) and secondary (MTS) lung cancers to assess what lessons could be learned from our experience. MATERIALS AND METHODS: We analysed 100 lesions (mean size 23 mm) in 81 patients (25 NSCLC/56 MTS). On the basis of the clinical-radiological evolution, we analysed complete ablation (CA) versus partial ablation (PA) at the first computed tomography (CT) scan and during the follow-up (mean 23 months), time to progression (TTP) and survival. Possible predictive factors for local effectiveness and survival were sought. RESULTS: At the first CT scan CA was obtained in 88 %; the difference between the mean diameter of lesions achieving CA and PA was significant (20 versus 38 mm; p = 0.0001). A threshold of 30 mm (p = 0.0030) and the histological type (NSCLC 75 %/MTS 94 %; p = 0.0305) were also predictive of CA. A total of 18.4 % of the CA recurred (average TTP 19 months). Survival at 1, 2 and 3 years was 84.5, 65.4 and 51.5 %, respectively. The predictors of survival at 3 years were the coexistence of other MTS (p = 0.0422) and a diameter <20 mm (p = 0.0323), but not the local effectiveness of RFA. CONCLUSION: RFA for thoracic malignancies is accurate for lesions up to 30 mm, especially if metastatic; survival is more closely related to staging factors than to the local effectiveness of RFA. PMID- 24234186 TI - Toward a definition of dyslexia. PMID- 24234187 TI - Serial rapid naming skills in children with reading disabilities. AB - This study compared the performance of children with reading disability (RD) and normal reading achievement (NRA) on tasks of serial rapid naming, verbal fluency, letter-based word retrieval, and articulatory speed. The groups, composed of children at two discrete age levels, one younger and one older, were matched for age, gender, and neighborhood school. Analyses of the on-line measurement of the children's serial rapid naming indicated that the children with RD had significantly larger reaction times and production durations than their NRA peers despite similar levels of accuracy. They also performed significantly worse on the categorical verbal fluency task, the letter-based word retrieval task, and the test of articulatory speed. The findings suggest that both access and post access processes, such as oral-motor inefficiency that extends the duration of word production, may be implicated in the slower serial rapid naming that has typified many samples of children with RD. PMID- 24234188 TI - Evidence for phonological processing deficits in less-skilled readers. AB - Although weaknesses in metaphonological skills are well-documented in poor readers, prior studies have yielded inconsistent findings as to whether less skilled readers also have deficits in the more primary phonological processes entailed in verbal working memory and speech production tasks. The present study was designed to examine this issue by comparing less-skilled third-graders readers (n=30) with younger children at the same reading level (n=30) and with more-skilled agemates (n=30) on a variety of tasks that require phonological processing (i.e., three "verbal memory" tasks [word span, span with concurrent processing, pseudoword imitation] and three "speech production" tasks [word-pair repetition, tongue twisters, rapid naming]). The results were striking: the less skilled third-grade readers had significantly lower accuracy scores than both their agemates and the younger normal readers on the word span, pseudoword imitation, word-pair repetition, and tongue twister tasks. Measures of accuracy were more related to reading ability than were measures of speed. Performance on a pseudoword imitation task was the variable most strongly linked to reading achievement. PMID- 24234189 TI - Predicting reading ability over the long term: The changing roles of letter naming, phonological awareness and orthographic processing. AB - A cohort of 92 children was followed through sixth grade to investigate the relationship of preschool skills and first grade phonological awareness to reading and spelling. In particular, the focus was on the changing roles of letter naming, orthographic awareness, and phonological processing in prediction, as reading experience increased. Preschool letter naming was a consistently significant predictor of reading vocabulary, reading comprehension, and spelling at each grade level, but the preschool orthographic task contributed most to reading comprehension and spelling at the higher grades. Conversely, the contribution of the first grade phonemic awareness measures to reading skills dropped sharply after third grade, although they continued to contribute to spelling prediction. When preschool precursors of phonological processing were examined, letter naming was found to be a predictor of first and third grade phonemic awareness. Findings confirm the importance of letter naming as a predictor and of the role of phonemic awareness in early reading acquisition, but also highlight the contribution of orthographic processing skills to later reading. PMID- 24234190 TI - Computer-based phonological awareness and reading instruction. AB - Reading with Orthographic and Segmented Speech (ROSS) programs use talking computers to deal with deficits in word recognition and phonological awareness. With ROSS, children read stories on a computer screen. Whenever they encounter a word they find difficult, they can request assistance by targeting the word with a mouse. The program highlights the word in segments and then pronounces the segments in order. In previous studies, children improved in reading, but children with relatively lower initial phonological awareness (PA) gained less than the others. In order to maximize the benefits from ROSS for all children, the current study aimed to improve PA before and while reading with ROSS, by using some programs based on theAuditory Discrimination in Depth method (Lindamood and Lindamood 1975), and others focusing on phoneme manipulation with speech feedback for all responses. The study compared the effects of this training with training in Comprehension Strategies (CS) based on Reciprocal Teaching techniques (Palincsar and Brown 1984), among second- to fifth-grade students with problems in word recognition. While both groups received equal instructional time in small-groups and with the computer, the groups differed in how much time they spent reading words in context. Whereas PA children spent half their computer time on PA exercises involving individual words and half reading words in context with ROSS, the CS group spent all their computer time reading words in context with ROSS. Both groups made significant gains in decoding, word recognition, and comprehension; however the PA groups gained significantly more than the CS group on all untimed tests of phoneme awareness, word recognition, and nonsense word reading. The CS children performed better on a test of time limited word recognition; they also achieved higher comprehension scores, although only while reading with a trainer. The PA children's improved decoding skill led to greater accuracy, but slower responses with difficult words, after one semester's training. PMID- 24234191 TI - Assistive technology for postsecondary students with learning disabilities: From research to practice. AB - The article reports on a support services program for postsecondary students with learning disabilities that was found to be particularly conducive to the conversion of research findings into practical applications in such a way that it measurably enhanced students' immediate and long-term academic performance. The results of both clinical and controlled research on persons with learning disabilities were applied to: (1) the prescription of services and compensatory strategies, including assistive technology, in relation to the diagnosis of specific disabilities; and (2) the preparation of a written composition curriculum for persons with learning disabilities which emphasizes the use of assistive computer technology. The paper concludes with an identification of those elements in the setting that appeared to promote the collaboration of both researchers and practitioners. These included: (1) location of the research staff both geographically and administratively within the service delivery unit; and (2) specific opportunities to accomplish joint goals that required intense communication and interaction. PMID- 24234192 TI - Applying effective instructional strategies for teaching dyslexic students in a remedial college algebra course. AB - For many secondary and postsecondary students with dyslexia, passing required algebra courses presents a formidable challenge. Although dyslexic students do have specific and sometimes severe learning deficits that can affect their chances of success in algebra, they can succeed if given appropriate and effective instruction that meets their special and individual needs. This article briefly describes the application of effective instructional practices to the teaching of remedial algebra that have been used with dyslexic students in the University of Wisconsin Oshkosh Project Success program. PMID- 24234193 TI - Morphological usage and awareness in children with and without specific language impairment. AB - In order to investigate the relationship between oral language usage and morphological awareness, 5- to 7-year-old children with specific language impairment (SLI) were compared to age-matched (AM) and language-matched (LM) comparison groups on a variety of measures requiring metalinguistic skill. These included sentence completion (involving real and nonsense words); comprehension of inflected non-words; response to morphological errors (including judgment, identification, and repair), and deliberate creation of grammatical violations. Overall, the SLI children performed significantly worse than their AM peers and were indistinguishable from younger LM children, suggesting that morphological awareness is more closely allied with oral language than with general cognitive/chronological development. PMID- 24234194 TI - Examining the linguistic coding differences hypothesis to explain individual differences in foreign language learning. AB - In this paper, it is suggested that foreign language learning problems result from difficulties with native language learning and hypothesized that difficulties with phonological processing may be the locus of foreign language learning difficulties for some poor foreign language learners. Evidence is described that supports these positions. It is argued that conceptualizing foreign language learning problems as alanguage problem allows researchers to more clearly specify deficits related to the learning of a foreign language. Research evidence which shows that good and poor foreign language learners exhibit significantly different levels of native language skill and phonological processing is summarized. Finally, potential challenges to my hypotheses as an explanation for foreign language learning problems are reviewed. PMID- 24234195 TI - An examination of language learning disabilities in youth with psychiatric disorders. AB - This study examined the relationship between psychiatric and language disorders in a sample of youth who were hospitalized at a private psychiatric hospital. Ninety six participants were given a test battery that consisted of tests measuring phonology, syntax, and semantics. The resulting sample scored in the average range on IQ measures and in the low-average to below-average range on written language abilities tests. Over 33% of the participants qualified for the diagnosis of a language learning disability (LLD); however, only 44% of those participants who qualified as LLD were receiving special education services upon admission. The participants who had both a psychiatric and LLD exhibited significant deficits in both phonology and syntax. General implications for identification and treatment are presented. PMID- 24234196 TI - A study of medical students and physicians referred for learning disabilities. AB - This study presents descriptive data on 86 medical students and physicians, referred for testing to determine the presence and type of learning problems. The major results indicate that most subjects had either a learning disability or attention deficit hyperactivity disorder (ADHD). Twenty-one subjects had a reading learning disability (LD); 21 subjects had a potential visual/spatial learning problem; 10 subjects had ADHD; 15 subjects had both a reading disability and ADHD; and 19 subjects had no detectable problem. Subtest analysis or WAIS-R scores indicated that sequential information processing may be the major difficulty for this sample. PMID- 24234198 TI - Forword. PMID- 24234197 TI - Progress in the measurement of laterality and implications for dyslexia research. AB - Much of contemporary laterality research has been motivated by a need to increase the accuracy with which individuals can be classified as left- or right hemisphere dominant for speech and language. Efforts to improve the classification accuracy of laterality methods have led not only to the refinement of laterality methods but also to the discovery of some of the mechanisms that contribute to asymmetric performance. Despite these advances, laterality methods still do not lead to definitive conclusions about hemispheric specialization in the individual case, and special caution must be used when interpreting results for individual dyslexic children. Event-related measurements of cerebral metabolism, still in the development phase, promise to complement but not replace behavioral laterality methods. PMID- 24234199 TI - Posterior fossa in primary microcephaly: relationships between forebrain and mid hindbrain size in 110 patients. AB - Microcephalies vary widely in clinical severity and in morphology. The purpose of this study is to determine the frequency of disproportion between the size of the cerebrum and the size of midbrain and hindbrain structures in infants and children with microcephaly, as analysis of such disproportions might aid understanding of these disorders and facilitate testing for specific genetic causes. The relative sizes of the forebrain, each component of the brain stem, and vermis and hemispheres of the cerebellum were analyzed visually on magnetic resonance (MR) images of 110 microcephalic patients. A disproportionally large cerebellum, compared with the cerebrum, was found in 50 cases (45.5%), a proportional cerebellum in 49 cases (44.5%), and a disproportionally small cerebellum in 11 cases (10%). Proportional cerebella were most common in mild (86%) and moderate (55%) microcephaly patients, whereas disproportionately large cerebella were most common in severe (57%) and moderate (32%) microcephaly. Disproportionately small cerebella were seen only in moderate (13%) and severe (9%) microcephaly. As genes are expressed at different times in cerebral and cerebellar development, it is postulated that analysis of relative cerebellar and brain stem size may be useful in the initial analysis of microcephaly by MR images both to categorize and to help determine likely genetic causes. PMID- 24234200 TI - On Finding the C in CBT: The Challenges of Applying Gambling-Related Cognitive Approaches to Video-Gaming. AB - Many similarities have been drawn between the activities of gambling and video gaming. Both are repetitive activities with intermittent reinforcement, decision making opportunities, and elements of risk-taking. As a result, it might be tempting to believe that cognitive strategies that are used to treat problem gambling might also be applied to problematic video gaming. In this paper, we argue that many cognitive approaches to gambling that typically involve a focus on erroneous beliefs about probabilities and randomness are not readily applicable to video gaming. Instead, we encourage a focus on other clusters of cognitions that relate to: (a) the salience and over-valuing of gaming rewards, experiences, and identities, (b) maladaptive and inflexible rules about behaviour, (c) the use of video-gaming to maintain self-esteem, and (d) video gaming for social status and recognition. This theoretical discussion is advanced as a starting point for the development of more refined cognitive treatment approaches for problematic video gaming. PMID- 24234201 TI - Toxic equivalency factors for dioxin-like PCBs. PMID- 24234202 TI - News from TNO : Reports from the Dutch Research Institutes for the Applied Natural Sciences. PMID- 24234203 TI - Ozone detector for European satellite use. PMID- 24234204 TI - Network looking for more economical clean-up of old toxic waste. PMID- 24234205 TI - Computer calculates exploding gas cloud. PMID- 24234206 TI - Immunoassay monitoring of polychlorinated biphenyls (PCBs) in the Great Lakes. AB - Although polychlorinated biphenyls (PCBs) are no longer manufactured, they are still entering the environment. In some compartments of the environment, PCB concentrations are a serious concern. This is especially true in compartments which accumulate PCBs, and in food items consumed by humans and wildlife. Also, there are situations in which management decisions require rapid, sensitive, accurate measurements, which can be made in real time under field conditions. Methods to use an enzyme-linked immunosorbent assay (ELISA) for PCBs were developed and applied to sediments and fish muscle homogenates collected from the Great Lakes. The extraction methods developed can be applied in the field with non-hazardous solvents, in the absence of sophisticated laboratory equipment. The method detection limit for PCBs in dimethyl sulfoxide (DMSO) extracts of sediment was 0.9 mg/kg. For PCBs in isopropanol extracts of fish tissue, the method detection limit was 0.6 mg/kg. The resolution of the ELISA was 0.83 mg/kg at 1.1 mg/kg and 1.6 mg/kg at 1.7 mg/kg, for sediment and fish tissue, respectively. PMID- 24234207 TI - Determination of atrazine in rainfall and surface water by enzyme immunoassay. PMID- 24234208 TI - Bioconcentration of superlipophilic persistent chemicals : Octachlorodibenzo-p dioxin (OCDD) in fish. AB - According to present understanding, persistent superlipophilic chemicals - such as octachlorodibenzo-p-dioxin, octachlorodibenzofuran, Mirex etc - with log Kow > 6 and cross sections > 9.5 A, bioconcentrate in aquatic organisms only little from ambient water. The most convincing argument against it is that in bioconcentration experiments with superlipophilic chemicals amounts applied exceeded water solubility by several orders of magnitude. This paper describes various methods for determining bioconcentration factors (BCF) of superlipophilic compounds. As exemplified with octachlorodibenzo-p-dioxin, BCF values evaluated by these methods match well with those calculated by QSARs for fish and mussels based on log Kow and water solubility. As expected, these BCF values exceed previous values by several orders of magnitude. For BCF evaluation of superlipophilic chemicals in aquatic organisms we recommend: (i) flow-through systems, kinetic method (OECD guideline No. 305 E) (ii) ambient concentrations < water solubility (iii) during the uptake and especially during the elimination phase no toxic effects of the test organisms should occur. PMID- 24234210 TI - Evaluation of fate and exposure models. PMID- 24234209 TI - Sorption kinetics of chlorinated hydrophobic organic chemicals : Part II: Desorption experiments. AB - This is the second of a two-part series describing the sorption kinetics of hydrophobic organic chemicals. Part I "The Use of First-Order Kinetic Multi Compartment Models" is published in issue 1 of this journal, pp. 21-28. Sorption kinetics of chlorinated benzenes from a natural lake sediment have been investigated in gas-purge desorption experiments. Biphasic desorption curves, with an initial "fast" part and a subsequent "slow" part, were found for all tested chlorobenzenes. From these results first-order sorption uptake and desorption rate constants were calculated with a two-sediment compartment model, which is presented in the first paper.In three sets of experiments the sorption uptake period and sediment/water ratio were varied. Rate constants are not influenced by these experimental conditions, which supports the partitioning concept for the sorption of hydrophobic organic chemicals in sediments. PMID- 24234212 TI - Tropoz II : Measurements of the distribution of air pollution over large areas. PMID- 24234211 TI - Pesticides and groundwater quality protection : Calibrating a simple model for ranking the contamination potential. AB - A simple approach for ranking the leaching of pesticides from surface soil is presented and tentatively calibrated with field data from an agricultural area. The approach is based on the calculation of a leaching index indicating the proportion of active ingredient, with respect to the quantity applied, leaching from a soil model in a given time interval (one year). In the selected area, 85 wells tapping an unconfined aquifer were sampled for groundwater pesticide residue analysis, in order to explore the index region between leachers and nonleachers. PMID- 24234213 TI - DuPont and EPA form partnership for waste reduction : Waste wi$e. PMID- 24234215 TI - Environmental hazard : Assessment of chemicals and products. PMID- 24234214 TI - The ocean as part of the global carbon cycle. AB - The ocean plays a central role in the global carbon cycle being by far the largest active reservoir. Atmospheric CO2 level depends on the CO2concentration in the ocean surface layer, which is relatively low compared to mean oceanic values due to biological and physical carbon pumps. Although the ocean may take up much of the carbon released by the increased burning of fossil fuels, this capacity is limited because of the chemical buffering and a mismatch in time scales (oceanic mixing is much slower than anthropogenic perturbations). PMID- 24234216 TI - Survey on the series : Abstracts of parts I-IV. PMID- 24234217 TI - Environmental Hazard- Assessment of chemicals and products : Part II: Persistence and degradability of organic chemicals. AB - Part II: Persistence and Degradability of Organic ChemicalsThe criteria "Persistence" and "Degradability" are defined and explained, starting from the "functional" definition of the environment. In this definition, theenvironment is the counterpart of thetechnosphere, which consists of all processes controlled by man. A substance is persistent if there are no sinks (degradation processes). It is shown that persistence is the central and most important criterium of environmental hazard assessment of organic chemicals. It follows that all substances released into the environment should be degradable, preferentially into small inorganic molecules (mineralization). As examples for persistent substances, the polychlorinated biphenyls (PCB), the chlorofluorohydrocarbons (CFC), bis (2-ethylhexyl) phthalate (DEHP), and 2,3,7,8-tetrachloro-dibenzo dioxin (TCDD) are discussed. Finally, an attempt to quantify persistence is made. PMID- 24234218 TI - Environmental risk assessment of existing chemicals. AB - Most of the existing chemicals of high priority have been released into the environment for many years. Risk assessments for existing chemicals are now conducted within the framework of the German Existing Chemicals Program and by the EC Regulation on Existing Substances. The environmental assessment of a chemical involves: a) exposure assessment leading to the derivation of a predicted environmental concentration (PEC) of a chemical from releases due to its production, processing, use, and disposal. The calculation of a PEC takes into account the dispersion of a chemical into different environmental compartments, elimination and dilution processes, as well as degradation. Monitoring data are also considered. b) effects assessment. Data obtained from acute or long-term toxicity tests are used for extrapolation on environmental conditions. In order to calculate the concentration with expectedly no adverse effect on organisms (Predicted No Effect Concentration, PNEC) the effect values are divided by an assessment factor. This assessment factor depends on the quantity and quality of toxicity data available. In the last step of the initial risk assessment, the measured or estimated PEC is compared with the PNEC. This "risk characterization" is conducted for each compartment separately (water, sediment, soil, and atmosphere). In case PEC > PNEC an attempt should be made to revise data of exposure and/or effects to conduct a refined risk characterization. In case PEC is again larger than PNEC risk reduction measures have to be considered. PMID- 24234219 TI - The new Swiss Environment Protection Law : Federal council favours a modern and internationally progressive Environment Law. PMID- 24234220 TI - The European Science Foundation (ESF). PMID- 24234221 TI - The challenge of waste : Strategies for waste reduction and waste management in chemical industry Vienna, Austria, September 23-25, 1993. PMID- 24234223 TI - Detecting new Buffel grass infestations in Australian arid lands: evaluation of methods using high-resolution multispectral imagery and aerial photography. AB - We assess the feasibility of using airborne imagery for Buffel grass detection in Australian arid lands and evaluate four commonly used image classification techniques (visual estimate, manual digitisation, unsupervised classification and normalised difference vegetation index (NDVI) thresholding) for their suitability to this purpose. Colour digital aerial photography captured at approximately 5 cm of ground sample distance (GSD) and four-band (visible-near-infrared) multispectral imagery (25 cm GSD) were acquired (14 February 2012) across overlapping subsets of our study site. In the field, Buffel grass projected cover estimates were collected for quadrates (10 m diameter), which were subsequently used to evaluate the four image classification techniques. Buffel grass was found to be widespread throughout our study site; it was particularly prevalent in riparian land systems and alluvial plains. On hill slopes, Buffel grass was often present in depressions, valleys and crevices of rock outcrops, but the spread appeared to be dependent on soil type and vegetation communities. Visual cover estimates performed best (r 2 0.39), and pixel-based classifiers (unsupervised classification and NDVI thresholding) performed worst (r 2 0.21). Manual digitising consistently underrepresented Buffel grass cover compared with field- and image-based visual cover estimates; we did not find the labours of digitising rewarding. Our recommendation for regional documentation of new infestation of Buffel grass is to acquire ultra-high-resolution aerial photography and have a trained observer score cover against visual standards and use the scored sites to interpolate density across the region. PMID- 24234224 TI - Application of nanoclay for preconcentration of ultra trace amounts of palladium in environmental samples prior to its determination by ETAAS. AB - In the present work, a batch preconcentration technique using nanoclay with 5-(4 dimethylaminobenzylidene)rhodanine coupled with electrothermal atomic absorption spectrometry was developed for the separation and determination of trace amounts of palladium. In this method, the sample solution was stirred with nanoclay as an adsorbent. Then, adsorbed palladium was subsequently eluted with HCl in acetone (1.5 mol L-1) and, finally, this eluate was injected to electrothermal atomic absorption spectrometry. Under the optimum conditions, the limit of detection and linear dynamic range were found to be 2.6 and 10.0-133 ng L-1 (in original solution), respectively. Furthermore, the enrichment factor and relative standard deviation of seven replicate determinations were 148 and +/-5.1 %, respectively. This suggested method is simple, selective and sensitive and can be applied to the extraction and determination of palladium in water, tea leaves, synthetic sample and certified reference material with satisfactory results. PMID- 24234225 TI - Effect of new organic supplement (Panchgavya) on seed germination and soil quality. AB - We studied the suitability of Panchgavya (five products of cow), new organic amendment, application on seed germination, plant growth, and soil health. After characterization, Panchgavya was mixed with water to form different concentration and was tested for seed germination, germination index, and root and shoot growth of different seedlings. Four percent solution of Panchgavya was applied to different plants to test its efficacy. Panchgavya and other two organic amendments were incorporated in soil to test the change of soil chemical and microbiological parameters. Panchgavya contained higher nutrients as compared to farm yard manure (FYM) and vermicompost. Its application on different seeds has positively influenced germination percentage, germination index, root and shoot length, and fresh and dry weight of the seedling. Water-soluble macronutrients including pH and metal were positively and negatively correlated with the growth parameters, respectively. Four percent solution of Panchgavya application on some plants showed superiority in terms of plant height and chlorophyll content. Panchgavya-applied soil had higher values of macro and micronutrients (zinc, copper, and manganese), microbial activity as compared to FYM, and vermicompost applied soils. Application of Panchgavya can be gainfully used as an alternative organic supplement in agriculture. PMID- 24234227 TI - Affinity separation of enzymes from mixtures containing suspended solids : Comparisons of magnetic and nonmagnetic techniques. AB - Agarose beads containing immobilized enzymes or affinity ligands have been made magnetically responsive by adsorbing freshly precipitated magnetite on their surface. These beads are used for affinity adsorption of proteins from complex mixtures containing suspended solids. The magnetically responsive beads and the unwanted (diamagnetic) solids are then separated by magnetic filtration. This magnetic adsorption scheme for direct affinity separation of enzymes from mixtures containing suspended solids is compared with a similar, but nonmagnetic, scheme in which the affinity matrix is supported on fiberglass cloth. The enzyme is allowed to adsorb in this matrix, and the matrix is simply removed physically from the suspension to achieve separation from the unwanted solids. The two methods seem comparable in their ability to separate a desired enzymatic activity. The magnetic methods are technically the more complex of the two, but are significantly the more rapid. The efficiency of separation of diamagnetic and ferrimagnetic solids in these biological systems by high gradient magnetic filtration is good. PMID- 24234226 TI - Netrin-1 attenuates cardiac ischemia reperfusion injury and generates alternatively activated macrophages. AB - Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Netrin-1 is a laminin-related protein identified as a neuronal guidance cue and netrin-1 expressed outside the nervous system inhibits migration of leukocytes in vitro and in vivo and attenuates inflammation-mediated tissue injury. In our study, hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. We found that netrin-1 decreased cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by netrin-1 administration. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with netrin-1 administration (IR + Netrin-1: 59.9 +/- 5.78 ml/min; IR: 26.2 +/- 4.3 ml/min; P < 0.05). Netrin-1 treatment increased expression of the alternatively activated macrophage (AAM) markers arginase-1 (Arg-1) and mannose receptor (MR) and promoted proliferator-activated receptor gamma (PPARgamma) expression in cardiac allograft. Furthermore, decreased TnT expression and reduced allograft infiltration of neutrophils and monocytes/macrophages by netrin-1 was abolished with addition of PPARgamma antagonist. In conclusion, netrin-1 attenuates cardiac IR injury and generates AAM which contributes to the protective effect of netrin-1. PMID- 24234228 TI - Kinetics of immobilized pig heart fumarase. AB - The kinetics of immobilized pig heart fumarase are described and compared with the properties of the enzyme free in solution.1.An analogous pH dependence of initial activity is found for free and immobilized enzyme.2.Immobilized and free fumarase deviate from classical Michaelis-Menten kinetics in the same way. The apparent Km values are three to eight times higher for the immobilized (2 mg/g gel) enzyme.3.The specific activity of immobilized fumarase is dependent on the final enzyme concentration on the gel; normal specific activities are observed when 50 [Symbol: see text]g fumarase is immobilized per gram of gel, whereas the specific activity decreases with increasing enzyme concentration.4.The activation energies for free and immobilized fumarase (50 [Symbol: see text]g/g gel) were found to be identical between 22 and 32?C and with L-malate as substrate (Ea = 12,290 cal/mol at pH 7.9). Upon increasing the concentration of fumarase on the gel, the activation energy decreases. Our results indicate that the true catalytic properties of fumarase are not affected by immobilization of this enzyme. The slight differences observed when fumarase is immobilized at concentrations higher than 50 [Symbol: see text]g/g gel must be attributed to diffusional limitation at the surface of the Sepharose matrix. PMID- 24234229 TI - Isolation of an urate-binding protein by affinity chromatography. AB - This paper describes an affinity chromatography procedure to purify an urate binding protein from human serum. The specific ligand was 8-amino-2,6 dihydroxypurine bound to Sepharose through the amino group. The specific elution was obtained with an uric acid or allopurinol solution. Electrophoretic analysis of the eluted protein shows a single sharp band with an alpha2-globulin mobility. Molecular weight, determined by gel filtration, is approximately 70,000 daltons. PMID- 24234230 TI - Temperature-dependent behavior of immobilized alkaline phosphatase. I. Role of working conditions and pH during coupling. AB - Alkaline phosphatase from hog intestine was immobilized to controlled-pore glass under various conditions. The specific activity of the enzyme was not diminished by immobilization. The influence of temperature and pH on the behavior and the stability of the immobilized enzyme preparations is discussed and compared to that of the native enzyme. PMID- 24234231 TI - Recent progress in plant cell culture : Research on the production of useful plant metabolites in Japan. AB - CONCLUSIONS: Commercial application of plant cell cultures for the production of useful metabolites on a large scale has not yet been realized. However, some recently published papers and patents seem very attractive for industrial use because their results and techniques are apparently applicable to a large-scale production of metabolites. The author believes that commercial success using plant tissue cultures will be realized in the near future with advanced techniques if product selection is determined by economic and political principles.In 1982, the 5th International Congress of Plant Tissue and Cell Culture will be held in Japan and this undoubtedly will encourage research activity in our country. PMID- 24234232 TI - Patents and literature. PMID- 24234235 TI - Cyclic vomiting syndrome in adults. AB - Cyclic vomiting syndrome (CVS) is a functional disorder that can occur in all age groups. It is characterized by recurrent stereotypic episodes of nausea and vomiting. Between these episodes are nausea-free intervals. Lack of awareness leads often to delay in making the correct diagnosis. A specific test to identify patients with CVS is still missing. The correct diagnosis is based on the typical anamnestic report and the exclusion of other disorders that are associated with recurrent vomiting. Treatment of acute vomiting episode comprises antiemetic, antimigraine and sedative therapy. For prophylaxis of vomiting episodes, amitriptyline and propranolol are frequently used. PMID- 24234237 TI - Editorial introduction. PMID- 24234236 TI - Role of diffusion-weighted MRI: predicting axillary lymph node metastases in breast cancer. AB - BACKGROUND: Ultrasound (US) is probably the standard imaging procedure in most centers, and US-guided fine needle aspiration can be added if suspicious lymph nodes are found. However, US-guided fine needle aspiration is an invasive method to diagnose a metastasis and has showed relatively low sensitivity. In general, diffusion-weighted (DW) magnetic resonance imaging (MRI) has become an emerging technique for discriminating benign from malignant breast lesions in a short imaging acquisition time. PURPOSE: To evaluate the potential for using DW MRI with an apparent diffusion coefficient (ADC) value to predict axillary lymph node metastases in patients with invasive breast cancer. MATERIAL AND METHODS: This study enrolled 110 axillary lymph nodes from 110 consecutive women who were diagnosed with invasive breast cancer for preoperative breast MRI and US. The largest enhancing ipsilateral axillary lymph nodes were included in this study, and benign and metastatic axillary lymph nodes were compared according to the pathologic reports. The cut-off ADC value to differentiate between benign and metastatic axillary lymph nodes was evaluated with receiver-operating characteristic curve analysis. Diagnostic performance of ultrasound and DW MRI was calculated for enhancing lymph node in dynamic contrast-enhanced MRI. RESULTS: Nodal metastases were documented in 68 (62%) axillary lymph nodes. The mean size of metastatic axillary lymph nodes was larger than that of benign axillary lymph nodes (15.5 mm vs. 10.9 mm, P < 0.001). The mean ADC value (0.69 * 10(-3 )mm(2)/s) of the metastases was significantly lower than that of the benign axillary lymph nodes (1.04 * 10(-3 )mm(2)/s) (P < 0.001). The ADC value cut-off between metastatic and benign axillary lymph nodes was 0.90 * 10(-3 )mm(2)/s. Using ADC cut-off, sensitivity, specificity, and accuracy of DW MRI were 100%, 83.3%, and 93.6%, respectively. The sensitivity, specificity, and accuracy of US showed 94.1%, 54.8%, and 79.1%, respectively. CONCLUSION: DW MRI of axillary lymph nodes can provide reliable information for the differentiation of benign from metastatic axillary lymph nodes in invasive breast cancer patients. PMID- 24234234 TI - Cysteine cathepsins in neurological disorders. AB - Increased proteolytic activity is a hallmark of several pathological processes, including neurodegeneration. Increased expression and activity of cathepsins, lysosomal cysteine proteases, during degeneration of the central nervous system is frequently reported. Recent studies reveal that a disturbed balance of their enzymatic activities is the first insult in brain aging and age-related diseases. Leakage of cathepsins from lysosomes, due to their membrane permeability, and activation of pro-apoptotic factors additionally contribute to neurodegeneration. Furthermore, in inflammation-induced neurodegeneration the cathepsins expressed in activated microglia play a pivotal role in neuronal death. The proteolytic activity of cysteine cathepsins is controlled by endogenous protein inhibitors the cystatins-which evidently fail to perform their function in neurodegenerative processes. Exogenous synthetic inhibitors, which may augment their inhibitory potential, are considered as possible therapeutic tools for the treatment of neurological disorders. PMID- 24234238 TI - The Amish: Perceptions of genetic disorders and services. AB - Previous studies of the closed Amish population have proven to be valuable in the field of genetics, however they have not explored the Amish parents' opinions and attitudes concerning genetic conditions and services. This exploration is necessary in order to provide culturally sensitive health care to a population at an increased risk for certain genetic conditions. The purpose of the present study was to examine the Amish population's general knowledge of genetic disorders, services, and the terminology used in describing inherited conditions, as well as their attitudes toward medical care and ethical and reproductive issues. Information was obtained from 17 Amish families, 12 who had an incidence of a genetic condition and five who had one or more children with other special health care needs, during personal interviews conducted in their homes in Lancaster, Pennsylvania. Results of the interviews showed that the birth of an affected child did not deter subsequent reproduction, that the majority of the parents were never offered genetic counseling or prenatal testing, and that the parents are interested in understanding the cause of their children's problems and recurrence risks. PMID- 24234239 TI - Professional preparation of individuals who provide genetic counseling services. AB - An unprecedented increase has occurred in demand for genetic counseling services during the current decade. This study examined the complex issue of who currently provides genetic counseling services and the professional preparation of these personnel. A self-administered questionnaire was mailed to 325 genetic counseling professionals in the southeastern United States who were members of the Southeast Regional Genetics Group (SERGG), National Society of Genetic Counselors, or American Society of Human Genetics States; 204 completed the questionnaire (63%). Seventy percent of respondents were female and 30% were male. Thirty percent of respondents held MD degrees; nine physicians held PhD degrees. Most physicians were male. Thirty-two percent of respondents held master's degrees in genetic counseling; five counselors held PhD degrees. Twenty-three percent of respondents were nurses; eight nurses held master's degrees. Three percent of respondents were social workers. Individuals with other degrees, such as an associate of science in medical technology and a doctoral degree in education, also provided genetic counseling. Genetic counseling typically involved a team effort, consisting mainly of physicians and genetic counselors. Most respondents reported college coursework in human genetics, supervised training, and seminar/workshop training. Thirty percent reported college coursework in counseling techniques, supervised training, and seminar/workshop training. Policy recommendations are offered concerning professional preparation of genetic counselors. PMID- 24234240 TI - Counseling for 5p- and neural tube defects. PMID- 24234241 TI - Update on the issue of sexual harassment. PMID- 24234242 TI - Does the Incidence of Adenocarcinoma of the Esophagus and Gastric Cardia Continue to Rise in the Twenty-First Century?-a SEER Database Analysis. AB - BACKGROUND: The rising incidence and histological change to adenocarcinoma in esophageal cancer over the past four decades has been among the most dramatic changes ever observed in human cancer. Recent reports have suggested that its increasing incidence may have plateaued over the past decade. Our aim was to examine the latest overall and stage-specific trends in the incidence of esophageal adenocarcinoma. PATIENTS AND METHODS: We used the Surveillance Epidemiology and End Results (SEER) database of the National Cancer Institute to identify all patients with adenocarcinoma of the esophagus and gastric cardia between 1973 and 2009. Both overall and stage-specific trends in incidence were analyzed using joinpoint regression analysis. RESULTS: The overall incidence of adenocarcinoma of the esophagus and the gastric cardia increased from 13.4 per million in 1973 to 51.4 per million in 2009, a nearly 400 % increase. Jointpoint analysis demonstrated that the yearly increase in incidence has slowed somewhat from 1.27 per million before 1987 to 0.97 between 1987 and 1997 and 0.65 after 1997. Stage-specific analysis suggests that the incidence of noninvasive cancer has actually declined after 2003 with a yearly decrease of 0.22. The percentage of patients diagnosed with in situ cancer declined after 2000 and remained under 2.5 % through the study period. CONCLUSIONS: The incidence of esophageal adenocarcinoma continues to rise in the USA. The percentage of patients diagnosed with in situ cancer has declined in the twenty-first century. PMID- 24234243 TI - Long-term patient outcomes after laparoscopic anti-reflux procedures. AB - BACKGROUND: Laparoscopic anti-reflux surgery with or without large hiatal hernia has been shown to have good short-term outcomes. However, limited data are available on long-term outcomes of greater than 5 years. The aim of this study is to review functional and symptomatic outcomes of anit-reflux surgery in a large tertiary referral medical center. METHODS: Two hundred ninety-seven patients who underwent anti-reflux surgery at the University of Nebraska Medical Center between 2002 and 2013 were included in this study. Patient data including pre- and post-operative studies and symptom questionnaires were prospectively collected and the database was used to analyze postoperative outcomes. RESULTS: A total of 297 Nissen fundoplications, 35 redo fundoplications and 22 Toupet procedures were performed. Mean BMI was 30.0 +/- 6.2. The median follow-up was 70 (6-135) months. There were three reoperations (0.9 %) for recurrent symptoms. Mesh was used in 210 cases where hiatal hernia was larger than 2 cm. Median preoperative DeMeester score was 50.8 +/- 46. There was a statistically significant improvement in composite heartburn score (83 % (CI 78.2, 87.7); p < 0.05), regurgitation (81.1 % (CI 76.1, 86.1); p < 0.05), and belching (63 % (CI 56.7, 69.3); p < 0.05). Atypical presentation such as pulmonary (e.g., aspiration (25.8 % (CI 20, 31.6), wheezing (20.3 % (CI 15, 25.6); p < 0.05), and throat symptoms (e.g., laryngitis 28 % (CI 22.1, 33.9); p < 0.05) also improved. Available radiographic studies for patients more than 3 years follow-up show an overall recurrence of 33.9 % (47.8 % in hiatal hernia > 5 cm repaired with mesh). Of those with recurrence, over 84 % were asymptomatic at follow-up. CONCLUSIONS: This study shows that patients had excellent symptom control and low rates of complications and reoperations in long-term follow-up. We found that typical gastro intestinal symptoms responded better compared with atypical symptoms in spite of clear evidence of reflux on preoperative studies. Hiatal hernia was very commonly seen in our patient population and long-term radiographic follow-up suggest that asymptomatic recurrence may be high but rarely requires any surgical intervention. Anti-reflux surgery with correction of hiatal hernia if present is safe and effective in long-term follow-up. PMID- 24234244 TI - Trends in treatment and survival in older patients presenting with stage IV colorectal cancer. AB - INTRODUCTION: Trends in the use of modern chemotherapeutic regimens, primary tumor resection, and the timing of chemotherapy and resection in older patients with stage IV colorectal cancer have not been evaluated. METHODS: We used Cancer Registry- and Medicare-linked data (2000-2009) to describe time trends in resection of the primary tumor and receipt of chemotherapy in patients >= 66 presenting with stage IV colorectal cancer (N = 16,168). RESULTS: The mean age was 77.8 +/- 7.3 years; 53.8 % were women and 82.9 % were white. Primary cancer sites were colon in 83.4 % and rectum in 16.6 %. Resection of the primary tumor decreased from 64.6 to 57.1 % (P < 0.0001) from 2001 to 2009. Systemic chemotherapy was given to 45.1 % of the patients. While the use of chemotherapy was stable over time (P = 0.48), the use of modern regimens containing oxaliplatin or irinotecan increased from 40.9 to 75.4 % (P < 0.0001). Bevacizumab use increased from 0.10 to 54.2 % (P < 0.0001). Survival improved by 4 % per year even after controlling for treatment and tumor location (HR = 0.96, 95 % CI 0.95 0.97). CONCLUSIONS: Survival in older patients with stage IV disease is improving over time. Surgical resection is still performed in the majority of patients. Resection rates decreased while modern chemotherapy was rapidly adopted perhaps suggesting a shift in practice patterns. PMID- 24234245 TI - Retrospective comparison of robot-assisted minimally invasive versus open pancreaticoduodenectomy for periampullary neoplasms. AB - BACKGROUND: As with other open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) may result in decreased pain, fewer wound complications, and accelerated recovery. However, when used for periampullary cancers, it is also important to assess if MIPD offers comparable oncologic outcomes. METHODS: Technical and perioperative outcomes were compared between patients with a preoperative diagnosis of periampullary neoplasm offered MIPD or open pancreaticoduodenectomy (OPD) from November 2009 to July 2011. RESULTS: Fifty-six consecutive MIPD and OPD (28 each) procedures were analyzed. Comparing MIPD to OPD, significant differences included longer median procedure time (431 vs 410 min, p = .04) and fewer median lymph nodes harvested (15 vs. 20, p = .04). R0 resection rate tended to be lower (63 vs. 88%, p = .07) as well as surgical site infections (18 vs. 43 %, p = .08). Clinically significant pancreatic fistula rate was the same between groups (21%). Other outcomes such as narcotic pain medication use, length of stay, and 30-day readmission rates were also similar. CONCLUSIONS: MIPD is feasible with comparable technical success and outcomes to OPD. However, there is a learning curve to the procedure and further experience and prospective study will be required to better establish the oncologic efficacy of MIPD to open resection. PMID- 24234246 TI - Gastrectomy in advanced gastric cancer effectively palliates symptoms and may improve survival in select patients. AB - BACKGROUND: The role of gastrectomy in the face of incurable gastric cancer is evolving. We sought to evaluate our experience with incomplete (i.e., R2) gastrectomy in advanced gastric cancer. METHODS: We reviewed 210 locally advanced or metastatic gastric cancers (1992-2008). Patient characteristics and outcomes were compared between three groups: gastrectomy (N = 99), exploration without resection (N = 66), and no surgery (N = 45). RESULTS: Clinicopathologic characteristics were similar between groups. Symptoms successfully resolved after gastrectomy in 48 % with a complication rate of 32 % and mortality of 6 %. Overall median survival for all patients was 6.2 months: 10.0 months after gastrectomy, 4.1 months after exploration without resection, and 5.3 months for no surgery (p < 0.001). Perioperative complications were the only predictor of symptom resolution following resection (OR = 0.175). Resolution of symptoms (p < 0.001, Hazards Ratio (HR) = 0.09) and preoperative nausea/vomiting (p = 0.017, HR = 0.55) improved survival, while linitis plastica (p = 0.035, HR = 4.05) and spindle cell morphology (p = 0.011, HR = 1.98) were predictors of poor survival in patients undergoing resection. CONCLUSIONS: Gastrectomy in the setting of advanced gastric cancer may be useful in up to half of patients with an acceptable perioperative mortality rate. Symptom resolution offers a potential survival advantage but is dependent upon a complication-free course, so should only be considered selectively. PMID- 24234247 TI - The "Raison D'etre" of pyrrolizidine alkaloids inCynoglossum officinale: Deterrent effects against generalist herbivores. AB - In this study we tested whether pyrrolizidine alkaloids (PAs) ofCynoglossum officinale serve as antifeedants against herbivores. Total PA N-oxide extracts of the leaves significantly deterred feeding by generalist herbivores. Specialist herbivores did not discriminate between food with high and low PA levels. Three PAs fromC. officinale, heliosupine, echinatine, and 3'-acetylechinatine, equally deterred feeding by the polyphagous larvae ofSpodoptera exigua. Although the plants mainly contain PAs in their N-oxide form, reduced PAs deterred feeding byS. exigua more efficiently than PA N-oxides. On rosette plants, the monophagous weevilMogulones cruciger significantly consumed more of the youngest leaves, which had the highest PA level and the highest nitrogen percentage. Larvae ofEthmia bipunctella, which are oligophagous within the Boraginaceae, did not discriminate between leaves. All generalist herbivores tested significantly avoided the youngest leaves with the highest PA levels. In the field, the oldest leaves also were relatively more damaged by herbivores than the youngest leaves. It is hypothesized that the skewed distribution of PAs over the leaves of rosette plants reflects optimal defense distribution within the plant. PMID- 24234248 TI - Host microhabitat location by stem-borer parasitoidCotesia flavipes: the role of herbivore volatiles and locally and systemically induced plant volatiles. AB - The origin of olfactory stimuli involved in the host microhabitat location inCotesia flavipes, a parasitoid of stem-borer larvae, was investigated in a Y tube olfactometer. The response of femaleC. flavipes towards different components of the plant-host complex, consisting of a maize plant infested with two or more larvae of the stem borerChilo partellus, was tested in dualchoice tests. The concealed lifestyle of the stem-borer larvae did not limit the emission of volatiles attractive to a parasitoid. A major source of the attractive volatiles from the plant-host complex was the stem-borer-injured stem, including the frass produced by the feeding larvae. Moreover, the production of volatiles attractive to a parasitoid was not restricted to the infested stem part but occurs systemically throughout the plant. The uninfested leaves of a stem-borer-infested plant were found to emit volatiles that attract femaleC. flavipes. We further demonstrate that an exogenous elicitor of this systemic plant response is situated in the regurgitate of a stem-borer larva. When a minor amount of regurgitate is inoculated into the stem of an uninfested plant, the leaves of the treated plant emit volatiles that attract femaleC. flavipes. PMID- 24234249 TI - Odors in traps: Does most recent occupant influence capture rates for house mice? AB - Responses of house mice (Mus domesticus) to odors in live traps were studied in a series of eight 0.1-ha outdoor field enclosures. It was assumed that the most recent mouse capture would provide the predominant odor in a trap for at least one week. Three different populations were tested, one in 1989 and two in 1992, involving over 800 different mice. Similar response patterns were recorded from all three groups. Two types of questions were tested: (1) Were there any biases contingent upon what had been previously caught? (2) Were there consistent responses of mice of particular age, sex, or reproductive classes to trap odors? Traps soiled by juvenile females caught adult females significantly less often than expected, but there were no consistent relationships in terms of the effects of specific residual odors on the subsequent capture at a particular trap. For various age, sex, and reproductive classes, (1) adult males preferred odors from juvenile and estrous females and avoided odors of other males significantly more than expected, (2) juvenile females selected traps with odors of other juvenile females and avoided all other types of female odors significantly more than expected, (3) nonestrous females exhibited a significant preference for adult male odor, and (4) estrous females selected traps containing odors from adult males but avoided those that had previously contained either nonestrous or pregnant/lactating females significantly more than expected. These findings have potential implications with regard to both the methods used for trapping small rodents and the social biology of house mice. PMID- 24234250 TI - Uptake and sequestration of ouabain and other cardiac glycosides inDanaus plexippus (Lepidoptera: Danaidae): Evidence for a carrier-mediated process. AB - Larvae ofDanaus plexippus feed almost exclusively on milkweed species of the genusAsclepias, whose characteristic secondary metabolites are cardiac glycosides (CGs). Aposematic last-instar larvae were fed with ouabain and other cardiac glycosides of differing polarities. Time course experiments show that ouabain is sequestered in the integument within 48 hr after feeding, whereas midgut tissue and hemolymph function as transient CG storage compartments. About 63% of ouabain was transferred from larvae to the butterflies, whereas 37% of ouabain was lost with larval and pupal exuviae and with the meconium. The main sites of storage in imagines are wings and integument. If mixtures of CGs are fed toD. plexippus larvae, differential sequestration can be observed: The polar ouabain contributes 58.8% of total CGs, followed by digitoxin (19.6%), oleandrin (10.6%), digoxin (4.9%), digoxigenin (4.6%) and proscillaridin A (1.5%). Thus, uptake and sequestration must be selective processes. Uptake of [(3)H]ouabain in vitro by isolated larval midguts was time-, pH-, and temperature-dependent and displayed an activation energy of 49 kJ/mol. Furthermore, the in vitro uptake of ouabain was inhibited (probably competitively) by the structurally similar convallatoxin. These data provide first evidence that ouabain uptake does not proceed by simple diffusion but with the aid of a carrier mechanism, which would explain the differential cardenolide uptake observed in living larvae. PMID- 24234251 TI - Home bedding modifies ultrasonic vocalization of infant bank voles. AB - Bank vole,Clethrionomys glareolus, pups, similar to many other infant rodents, emit ultrasonic vocalizations when they are removed from the nest and cooled. Infants exposed to bedding from their home cage produced fewer and shorter calls than infants tested without bedding. Sound frequencies were significantly higher in infants exposed to home bedding than in other experimental groups. These results provide evidence that infant bank voles are able to identify the presence of home bedding, probably on the basis of odor. This appears to be the first report of shifts in frequency of pup ultrasonic calls in response to olfactory cues. PMID- 24234252 TI - Browning-associated mechanisms of resistance to insects in corn callus tissue. AB - Callus of the fungus- and insect-resistant corn inbred, Mp313E, of differing ages and degrees of brownness was tested for effects on neonate larvae of the corn earworm,Helicoverpa zea. Older, browner, 8-week-old callus caused significantly higher mortality ofH. zea after two days compared to larvae fed 5-week-old callus (brown or not) or pinto bean diet. Larvae fed on the 5-week-old callus were significantly smaller after nine days compared to those fed on nonbrown callus of the same age. Ferulic acid,p-coumaric acid, and sinapic acid, corn allelochemicals associated with cell walls, were oxidized (produced a brown product) up to 10-fold more rapidly by peroxidase preparations of the brown callus compared to nonbrown callus. Peroxidase isozymes from both types of brown callus separated by conventional gel electrophoresis and isoelectric focusing showed more intense anodic/acidic bands compared to peroxidase isozymes separated from the nonbrown callus. Some additional peroxidase isozymes were also present in the brown callus and were able to oxidize ferulic acid. Conventional extraction techniques for phenolic acids indicated free ferulic acid levels were similar for same-age callus, but somewhat less for older callus; no freep coumaric acid was detected. For esterified and insoluble-bound phenolic content, the level ofp-coumaric acid was higher than that of ferulic acid and was somewhat greater in insoluble-bound fractions for the old callus compared to the younger callus. Color ratings of aqueous extracts and phenolic acid extract residues indicated much brown material remained, which was proportional in color to the original material. The differential insect response to, and peroxidase activity of, brown vs. nonbrown callus were similar to results previously noted for brown pericarps of corn compared to nonbrown pericarps. This information suggests the peroxidases are contributing to the browning through oxidation of phenolic acids and thereby enhancing resistance to insects. PMID- 24234253 TI - Effects of biotic and abiotic stress on induced accumulation of terpenes and phenolics in red pines inoculated with bark beetle-vectored fungus. AB - This study characterized the chemical response of healthy red pine to artificial inoculation with the bark beetle-vectored fungusLeptographium terebrantis. In addition, we sought to determine whether stress altered this induced response and to understand the implications of these interactions to the study of decline diseases. Twenty-five-year-old trees responded to mechanical wounding or inoculation withL. terebrantis by producing resinous reaction lesions in the phloem. Aseptically wounded and wound-inoculated phloem contained higher concentrations of phenolics than did constitutive tissue. Trees inoculated withL. terebrantis also contained higher concentrations of six monoterpenes,alpha pinene,beta-pinene, 3-carene, limonene, camphene, and myrcene, and higher total monoterpenes than did trees that were mechanically wounded or left unwounded. Concentrations of these monoterpenes increased with time after inoculation. Total phenolic concentrations in unwounded stem tissue did not differ between healthy and root-diseased trees. Likewise, constitutive monoterpene concentrations in stem phloem were similar between healthy and root-diseased trees. However, when stem phloem tissue was challenged with fungal inoculations, reaction tissue from root-diseased trees contained lower concentrations ofalpha-pinene, the predominant monoterpene in red pine, than did reaction tissue from healthy trees. Seedlings stressed by exposure to low light levels exhibited less extensive induced chemical changes when challenge inoculated withL. terebrantis than did seedlings growing under higher light. Stem phloem tissue in these seedlings contained lower concentrations ofalpha-pinene than did nonstressed seedlings also challenge inoculated withL. terebrantis. It is hypothesized that monoterpenes and phenolics play a role in the defensive response of red pine against insect-fungal attack, that stress may predispose red pine to attack by insect-fungal complexes, and that such interactions are involved in red pine decline disease. Implications to plant defense theory and interactions among multiple stress agents in forest decline are discussed. PMID- 24234254 TI - Absolute configuration of sex pheromone for tea tussock moth,Euproctis pseudoconspersa (strand)via synthesis of (R)- and (S)-10, 14-dimethyl-1 pentadecyl isobutyrates. AB - (R)- and (S)-10,14-dimethyl-1-pentadecyl isobutyrates were synthesized from (S)- and (R)-citronellols, respectively. TheR enantiomer was as active as the natural pheromone but theS enantiomer was less active in the electrophysiological analyses, which provided conclusive proof that the absolute configuration of the natural pheromone isR. PMID- 24234255 TI - Effects of mongoose odors on rat capture success. AB - Wild rats,Rattus norvegicus, R. exulans, andR. rattus, avoided wire-cage live traps that had previously captured mongooses,Herpestes auropunctatus. Replacing traps soiled by mongooses with clean traps would increase rat capture success and reduce a source of experimental bias. PMID- 24234256 TI - Differences in sex pheromone communication systems of closely related species:Spodoptera latifascia (walker) andS. descoinsi lalannecassou & silvain (Lepidoptera: Noctuidae). AB - S. latifascia andS. descoinsi are closely related species that occur sympatrically over limited areas in French Guiana. We examined allopatric populations,S. latifascia originating from Barbados andS. descoinsi from French Guiana. Studies on nocturnal activity cycles showed temporal partitioning of female calling behavior, male sexual activity, and mating behavior.S. descoinsi were sexually active in the first half of the scotophase whereasS. latifascia were sexually active in the second half. Seven compounds (Z9-14: Ac,Z9,E12-14: Ac,Z11-16: Ac,E9,E12-14: Ac,Z9-14: Ald,Z9,E11-14: Ac andZ11-14: Ac) were identified in females of bothS. latifascia andS. descoinsi extracts.Z9-14: Ac was a main pheromone component for the two species. The major difference between the pheromones ofS. latifascia andS. descoinsi was the proportion ofZ9,E12-14: Ac in the extracts: 7% forS. latifascia and 42% forS. descoinsi. The proportion ofZ9,E12-14: Ac relative to the sum ofZ9-14: Ac andZ9,E12-14: Ac in individual gland extracts was 4+/-1% (mean +/- standard deviation) forS. latifascia and 44.8+/-6% forS. descoinsi. Electrophysiological studies showed no major differences between species in the morphology and physiology of the pheromone receptors of males. Receptors were identified forZ9-14: Ac andZ9,E12-14: Ac, but no receptor was found for the other compounds. In the wind tunnel, synthetic blends withZ9-14: Ac andZ9,E12-14: Ac gave the same behavioral responses as conspecific female extracts for the males of the two species. Some cross attraction was observed with synthetic blends and female extracts. Nethertheless, previous field trapping experiments in French Guiana were species-specific and suggested differences in the attractivity of males. In the laboratory,S. latifascia andS. descoinsi could hybridize in both reciprocal crosses. FemaleS. descoinsi * maleS. latifascia mating rate was significantly lower than for the reciprocal cross, and 26.7% of femaleS. descoinsi could not separate from maleS. latifascia after mating. These copulatory problems may involve genital incompatibilities between males and females. Several barriers against interbreeding betweenS. latifascia andS. descoinsi seem to combine including differences in nocturnal activity cycles, pheromone differences, and genital barriers. The study of sympatric populations will be necessary to define the role of sex pheromones in the reproductive isolation ofS. latifascia andS. descoinsi. PMID- 24234257 TI - Role of EGFR as a prognostic factor for survival in head and neck cancer: a meta analysis. AB - The prognostic role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains controversial. The goal of this study was to summarize existing evidence regarding whether EGFR overexpression is a prognostic factor in HNSCC. Relevant studies were identified using Pubmed, Ovid, and Web of Science databases. A meta-analysis was conducted on the prognostic value of EGFR expression for overall survival (OS) and disease-free survival (DFS). Thirty-seven studies were included. Primary analysis indicated that EGFR overexpression was associated with reduced OS (hazard ratio [HR]: 1.694, 95% confidence interval [CI]: 1.432-2.004). DFS, on the other hand, was not associated with EGFR expression after adjusting for publication bias (HR: 1.084, 95% CI: 0.910-1.290). Subgroup analysis gave a statistically significant pooled HR for OS in laryngeal carcinoma (HR: 2.519, 95% CI: 1.615-3.928) and in oropharyngeal carcinoma (HR: 2.078, 95% CI: 1.605-2.690). The pooled HR was statistically significant for DFS with respect to oropharyngeal carcinoma (HR: 1.055, 95% CI: 1.020-1.092), but not laryngeal carcinoma (HR: 1.750, 95% CI: 0.911-3.360). When dividing studies based on the immunohistochemistry (IHC) scoring system, only the group that evaluated EGFR expression according to the intensity and extent of staining showed no between-study heterogeneity for both OS and DFS. Overall, EGFR overexpression was associated with shortened OS, but not DFS. Future studies are needed that stratify patients by specific tumor sites. Furthermore, when estimating protein level by the IHC method, it is advisable to consider both intensity and extent of staining. PMID- 24234258 TI - A pooled analysis of the ERCC2 Asp312Asn polymorphism and esophageal cancer susceptibility. AB - Published data regarding the association between the excision repair cross complimentary group 2 (ERCC2) Asp312Asn polymorphisms and esophageal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to assess the strength of association between the ERCC2 and esophageal cancer susceptibility using random effects model. We systematically searched PubMed, Embase and Web of Science with a time limit of September 15, 2013. Summary odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association between the ERCC2 Asp312Asn polymorphism and esophageal cancer susceptibility using random effects model. A total of seven case-control studies including 1,831 cases and 2,728 controls were included for analysis. Overall, a significant association was found between ERCC2 Asp312Asn polymorphism and esophageal cancer susceptibility for GA vs. GG (OR = 1.20, 95 % CI = 1.03-1.40) and for the dominant model GA/AA vs. GG (OR = 1.18, 95 % CI = 1.03-1.35). However, the ERCC2 Asp312Asn polymorphism was a protective factor for AA vs. GA/GG (OR = 0.63, 95 % CI = 1.15-2.65) in esophageal squamous cell carcinoma. Our meta-analysis suggested that the ERCC2 Asp312Asn polymorphism might be associated with increased risk of esophageal adenocarcinoma and a protective factor for esophageal squamous cell carcinoma. PMID- 24234259 TI - Psychological factors related to health, back pain, and dysfunction. AB - Psychosocial variables may be important determinants of experienced back pain as well as dysfunction. This paper reports on differences on a battery of psychosocial variables between women, from the same work place, off work because of back pain, having only back pain (not off work), and those without back pain. The groups suffering pain had similar levels of pain intensity and frequency and the covariates of age and work load were used in MANCOVA analyses. The results showed significant overall differences on the Coping Strategies Questionnaire, Handicap Index, Duke Health Profile, as well as items concerning family support and the relation of pain to work. Several variables differed between the Healthy group on the one hand and the two groups suffering pain on the other hand. However, coping strategies and perceived health produced significant differences between all three groups in univariate analyses. Unlike other studies the Work APGAR produced no significant results. These data suggest that work status is not directly related to pain intensity, but rather to an interaction between psychosocial factors and the pain experience. Future research should delineate which variables may be used in screening. PMID- 24234260 TI - Factors influencing ergonomic conditions and employment rate after an occupational musculoskeletal injury. AB - In 195 cases of musculoskeletal occupational injury individual and work related factors and their relationship with reduction of physical work load and active employment was studied. Data concerning the injuries were obtained and after 18 months the work places were assessed. Information on employment status was obtained by a postal questionnaire after 3 years. Multiple logistic regression was used to explain the two outcome measures. Injuries classified as diseases and informative injury reports were factors positively associated with reduction of work load. Male gender, higher education, and a sick-leave shorter than 6 months were factors positively associated with employment. PMID- 24234261 TI - Randomized study of the application of single motor unit biofeedback training to chronic low back pain. AB - The application of single motor unit biofeedback training (SMUBT) techniques was compared to traditional therapies in treating chronic low back pain (CLBP). Thirty-six volunteers (who experienced daily pain for 7 years in the T8 to S1 area) were randomly assigned to one of three treatments; SMUBT, relaxation training, or an educational program. The pain level and electromyographic activity of all subjects were assessed by a person blind to the treatment; before, immediately after, and 90 days after treatment. The SMUBT group reported immediately decreased pain which was maintained at 90 days, the relaxation group showed no changes, while the education group reported decreased pain at 90 days. The EMG results showed decreased amplitude and bilateral differences for the SMUBT and education groups. A 4-year follow-up revealed the SMUBT group remained symptom free. Implications and discussion of the results concludes the paper. PMID- 24234262 TI - Disability management and the cardiac rehabilitation patient: Job simulation and transitional work strategies. AB - Medical advances and treatment interventions among patients with coronary heart diseases have not resulted in more timely return to work outcomes among cardiac rehabilitation programs. This article reviews vocational rehabilitation outcomes among persons with coronary heart disease, and the importance of employer-based disability management concepts. Job simulation, transitional work strategies, and ergonomic job site modifications, when integrated within the cardiac rehabilitation protocol, may yield promising results. The article discusses an experimental research project at the University of Cincinnati Medical Center that addresses worker-work environment interaction, encourages direct employer involvement, and promotes employer accommodation under the Americans with Disabilities Act. PMID- 24234263 TI - Back problems are for life: Perceived vulnerability and its implications for chronic disability. AB - As part of a qualitative research study of the experience of work-related back problems, a series of in-depth ethnographic interviews were conducted with 15 workers receiving treatment for back injuries. Analysis of these data revealed that the workers perceived their back problems as lifelong problems. Many believed that their back injuries had permanently heightened their vulnerability to reinjury and chronic disability. Accommodating this sense of physical vulnerability required a redefinition of one's self and one's future. For some workers, the perceived threat of future back problems was itself disabling and appeared to discourage a return to normal social roles. Workers' interactions with the health care system shaped their perceptions of their bodies and their notions of the appropriate means to cope with their physical vulnerability. Implications of the perception of permanence for the development of chronic disability among workers who experience back problems are examined. PMID- 24234264 TI - How children learn to read and why they fail. AB - The present article considers the contrast between conceptions of reading as a natural and as an unnatural act, relying on the simple view of reading as a theoretical framework (Gough and Tunmer 1986). According to the simple view, reading comprehension is a product of both listening comprehension and decoding. Here it is argued that the comprehension aspect of reading depends on those same natural-forces that govern acquisition of spoken language, whereas decoding depends on explicit tutelage, with little evidence that children will induce the cipher from simple exposure to written words and their pronunciations (sight-word instruction). Rejecting both sight-word and phonics instruction as inadequate in and of themselves, evidence is reviewed suggesting that successful readers require explicit awareness of the phonological structure of spoken words, which can and should be taught in kindergarten, prior to formal reading instruction. Beyond this point, reading success depends on a modicum of phonics instruction together with extensive practice with reading itself. PMID- 24234265 TI - Handwriting: A neglected cornerstone of literacy. AB - This paper discusses the necessity for teaching children to have readable automatic handwriting. As demonstrated by a search of the literature, educational institutions in both the United States and Great Britain display a lack of concern about the importance of handwriting in school curricula. Researchers display a similar lack of concern as evidenced by the scarcity of major research studies on handwriting. They appear to be unaware of the benefits of effective early teaching. Often the choice of what to teach, how to teach, and when to teach is left up to the discretion of individual teachers, who typically have been given inadequate preparation for teaching handwriting. The decision of whether to begin with manuscript or cursive seems based on custom and opinion instead of any solid empirical evidence. The special needs of left-handed children and dyslexic children are seldom addressed. Yet, these children need to be taught handwriting meticulously. More attention needs to be focused on how all children can acquire the essential skill of legible serviceable handwriting. PMID- 24234266 TI - Coping with dyslexia in the regular classroom: Inclusion or exclusion. AB - The article begins with an historical review of the many attempts to cope with learning disabled and other handicapped children in schools, especially in regular classrooms. Children with dyslexia are reportedly the majority of individuals with learning disabilities. Most researchers have reached concensus that dyslexia originates with specific impairment of language processing. Although it would seem necessary for educators, especially those who teach the primary grades, to understand the structure of the English language and the alphabetic writing system, there is evidence that teachers are not required to have such command of language and how to teach it. The need for establishment of a comprehensive, interdisciplinary teacher education and training program will be discussed. This would include a core body of knowledge, relevant skills, and an understanding of methods, attitudes and values of participating disciplines. Without appropriate changes in teacher preparation it is doubtful that inclusion in regular classrooms will provide much educational benefit for the dyslexic population in our schools. PMID- 24234267 TI - Tennessee meets the challenge of dyslexia. AB - In 1993, the Tennessee General Assembly voted funds to establish a model unit of integrated services and research to address the full scope of issues associated with dyslexia. Dyslexia is characterized as significant difficulty in reading and spelling individual words. In the Tennessee Center for the Study and Treatment of Dyslexia, these problems are presumed to be the consequence of a phonological core deficit. When compared to typical readers, matched for age or reading level, dyslexic readers evidence average listening comprehension, a relative strength in reading comprehension, deficits in word recognition and spelling, and severe deficits in word analysis as well as in awareness and manipulation of phonemes. Integration of this information yields a diagnostic profile that may be applied in the differential diagnosis of dyslexia both in clinical and school settings. This paper presents an overview of the Tennessee Center for Dyslexia and the services it provides as well as its guidelines for interpreting the results of norm-referenced tests and criterion-referenced measures to diagnose dyslexia and plan appropriate intervention. Frith's (1985, 1986) developmental framework for reading acquisition is integrated with the assessment data to outline an instructional plan that addresses mastery of skills within and across the hierarchical phases-logographic, alphabetic, and orthographic-of reading development. PMID- 24234268 TI - Phono-Graphix(TM): A new method for remediating reading difficulties. AB - Eighty-seven children, 6 to 16 years of age, with reading and/or spelling difficulties were trained in a new program (Phono-Graphix(TM)) that emphasizes phoneme awareness training, sound-to-print orientation, curriculum design sequenced by orthographic complexity, and active parental supervision in homework assignments. The children's initial level of competence to access the alphabet code was revealed by diagnostic testing, and individualized sequences of instruction were developed. The children received 12 hours or less of one-to-one training, one hour per week. Children gained an average of 13.7 standard score points on word recognition (1.70 points per clinical hour) and 19.34 standard score points on nonsense word decoding (2.57 points per clinical hour). PMID- 24234269 TI - Language! Effects of an individualized structured language curriculum for middle and high school students. AB - This chapter documents the success of a 12-month individualized structured language curriculum (LANGUAGE!) provided to middle and high school juvenile offenders (n=45; 43 males; 2 females) enrolled in a rehabilitation program. Although individual students participated in the program for an average of just 22.7 weeks (SD 8.51), they made significant gains (more than three years growth) over this period in written language expression (composition), encoding (spelling), and decoding (isolated word recognition), as documented by standardized literacy measures, moving from standard scores in the 60s and 70s to the 80s and 90s. Gains on the Gray Oral Reading Test (GORT III) were consistent with these measures and well exceeded gains made by a comparison group (n=51; 48 males, 3 females) which included students attending similar rehabilitation programs for a comparable period of time, but these students were not offered the individualized LANGUAGE! curriculum. Details of the LANGUAGE! curriculum and the basis of its success are discussed. PMID- 24234270 TI - Analyzing cohesion in language samples of college students: A diagnostic tool. AB - This paper presents a clinically derived system of analyzing reading miscues of college students and comparing the observed patterns to a student's oral expressive language. By looking for consistencies and contrasting the observed patterns with what is now known about the cohesive development of language within and across its spoken and written forms, and by looking for places in which the expected continuity is not apparent in the individual case, we can identify many of the barriers to successful learning. An important attribute of the new technique is that it can be used in varied contexts. The contexts can be tailored to suit the actual coursework that a student does or will encounter and the analysis still provides comparative data. The method includes a system of giving assessment feedback to the students that allows for their input and therefore helps them identify with treatment recommendations that are being suggested to overcome long-standing learning blocks. PMID- 24234271 TI - Computer-based compensation of adult reading disabilities. AB - We studied the use of computer readers, and especially their speech synthesis component, as a compensatory tool for adults with dyslexia. We first explored the enhancement of reading skills in a group of college students and working adults. Their unaided reading was very slow, and most participants in the study could sustain reading for only short periods. Although their timed comprehension was poor, their untimed comprehension was above average. The computer reader enhanced the reading rate and comprehension of most participants and enabled them to sustain reading longer. The difference between aided and unaided reading rate was inversely proportional to the unaided rate. Slower readers experienced greater enhancement than faster ones. The enhancement of comprehension was also inversely proportional to unaided scores, and good predictions of the enhancement were obtained from multiple regression models that included scores from specific standard tests of auditory and visual cognitive abilities. We also explored the use of computer readers in the workplace and show through case studies that their use can have important positive effects on individual careers and self-confidence when specific conditions exist. Finally, we investigated the use of computer readers to supplement an adult remediation program. The readers allowed and motivated the students to read more and, as a result, to progress more rapidly. PMID- 24234272 TI - Phonological and semantic factors in the object-naming errors of skilled and less skilled readers. AB - Children who read poorly have difficulty naming objects, and their errors usually bear a semantic or a phonetic resemblance to the correct words. Excessive semantic and phonetic naming errors could both be due to underlying phonological deficiencies in poor readers. When children cannot name an object because its name is not represented well in long-term memory or cannot be processed well, semantic information as well as partially available phonological information may be used in selecting an alternative response. This hypothesis was tested by looking for the joint influence of semantics and phonology in the naming errors of third-grade children. The same children were asked to name a set of pictured objects, repeat the object names after being spoken by the examiner, and recognize the objects from their spoken names. A separate group of children produced associative responses to the same pictures. First, it was found that, compared with skilled readers, less-skilled readers who named objects without any time pressure had a deficit that could not be attributed to repetition difficulty or limited vocabulary. Second, the naming errors showed a semantic relationship to the correct words that was as strong as that of the associative responses. Third, the naming errors also showed a phonetic relationship to the correct words, whereas the associative responses did not. Finding a joint semantic and phonetic effect in the naming errors of children suggests that the errors may be attributable to phonological deficiencies. PMID- 24234273 TI - The role of morpheme recognition and morphological awareness in dyslexia. AB - This paper begins by presenting theoretical arguments and empirical evidence to support the idea that morpheme analysis strategies play a part in word recognition in reading, and in dyslexia in particular. The results of two studies are presented which indicate that dyslexic adolescents use recognition of root morphemes as a compensatory strategy in reading of both single words and coherent text. Furthermore, the evidence is reviewed that the use of morpheme recognition as a strategy in reading to some extent depends on the linguistic awareness of morphemes in spoken language. Finally, results from a pilot study of the effects of morphological awareness training of dyslexic students are presented which suggest that it may be possible to improve the awareness of morphology independently of phoneme awareness, and that such a training may have positive effects on reading of coherent text and on the accurate spelling of morphologically complex words. PMID- 24234274 TI - Gender differences in cognitive abilities of opposite-sex and same-sex twin pairs with reading disabilty. AB - In order to compare the pattern of gender differences for cognitive measures in opposite-sex twin pairs to that in independent samples of twins from same-sex pairs, psychometric test data were obtained from four research-identified samples of children: (1) 96 pairs of opposite-sex fraternal twins in which at least one member of each pair is reading disabled; (2) 62 pairs of opposite-sex fraternal twins with no history of reading problems; (3) 167 males and 155 females from same-sex identical and same-sex fraternal twin pairs in which at least one member of each pair is reading disabled; and (4) a comparison sample of 126 males and 132 females from same-sex twin pairs with no history of reading problems. Results of multivariate analyses indicate that gender differences for cognitive measures are similar in twin pairs with and without reading disabilities. Moreover, a highly similar pattern of gender differences occurs for opposite-sex twin pairs who shared both prenatal and early postnatal influences and for independent samples of children from different families. PMID- 24234276 TI - Foreword. PMID- 24234275 TI - Impaired performance of children with dyslexia on a range of cerebellar tasks. AB - It is now thought that the cerebellum is involved in the acquisition of "language dexterity" in addition to its established role in motor skill acquisition and execution. Mild cerebellar impairment, therefore, provides a possible explanation of a range of problems shown by children with dyslexia. The authors have established suggestive evidence in support of this hypothesis in tests of balance and of time estimation. In a further test of the hypothesis, a battery of clinical tests for cerebellar impairment, including tests of muscle tone and of coordination, was administered to matched groups of children with dyslexia and control children aged 10, 14, and 18 years (55 subjects in all). The children with dyslexia showed highly significant impairments on all the cerebellar tests, and significant impairment compared even with reading age controls on 11 of the 14 tasks. Deficits on the majority of tests were among the largest found in our research program. The findings, therefore, provide further intriguing evidence of cerebellar impairment in dyslexia. We speculate that the well-established phonological deficits in dyslexia may arise initially from inefficient articulatory control attributable to cerebellar impairment. PMID- 24234277 TI - Using contextual analysis to investigate the nature of spatial memory. AB - The present study investigated the properties of episodic spatial memory by conducting contextual analysis on spatial memory tasks in a large sample of individuals (N = 778) between the ages of 18 and 92. The results suggest that episodic spatial memory as measured by a dot location task is not uniquely influenced by memory but is strongly influenced by fluid ability (Gf). The spatial memory-Gf relationship is evident and robust even when spatial memory is operationalized with a very simple single-dot location task, suggesting that allocation of attention across space may play a role in the relationship. Results also indicate that the spatial memory-Gf relations are not dependent on complexity of processing, because Gf has a similar magnitude of relations with a more complex version of the dot location task. Collectively, the results suggest that spatial memory likely represents some aspect of fluid intelligence and is not uniquely related to measures of verbal memory. PMID- 24234278 TI - Alternative measures of spatial distribution and availability of health facilities for the delivery of emergency obstetric services in island communities. AB - International guidelines and recommendations for availability and spatial distribution of emergency obstetric care services do not adequately address the challenges of providing emergency health services in island communities. The isolation and small population sizes that are typical of islands and remote populations limit the applicability of international guidelines in such communities. Universal access to emergency obstetric care services, when pregnant women encounter complications, is one of the three key strategies for reducing maternal and newborn mortality; the other two being family planning and skilled care during labor. The performance of selected lifesaving clinical interventions (signal functions) over a 3-month period is commonly used to assess and assign performance categories to health facilities but island communities might not have a large enough population to generate demand for all the signal functions over a 3-month period. Similarly, availability and spatial distribution recommendations are typically based on the size of catchment populations, but the populations of island communities tend to be sparsely distributed. With illustrations from six South Pacific Island states, we argue that the recommendation for availability of health facilities, that there should be at least five emergency obstetric care facilities (including at least one comprehensive facility) for every 500,000 population, and the recommendation for equitable distribution of health facilities, that all subnational areas meet the availability recommendation, can be substituted with a focus on access to blood transfusion and obstetric surgical care within 2 hours for all pregnant residents of islands. Island communities could replace the performance of signal functions over a 3-month period with a demonstrated capacity to perform signal functions if the need arises. PMID- 24234279 TI - Preconception healthcare delivery at a population level: construction of public health models of preconception care. AB - A key challenge of preconception healthcare is identifying how it can best be delivered at a population level. To review current strategies of preconception healthcare, explore methods of preconception healthcare delivery, and develop public health models which reflect different preconception healthcare pathways. Preconception care strategies, programmes and evaluations were identified through a review of Medline and Embase databases. Search terms included: preconception, pre-pregnancy, intervention, primary care, healthcare, model, delivery, program, prevention, trial, effectiveness, congenital disorders OR abnormalities, evaluation, assessment, impact. Inclusion criteria for review articles were: (1) English, (2) human subjects, (3) women of childbearing age, (4) 1980-current data, (5) all countries, (6) both high risk and universal approaches, (7) guidelines or recommendations, (8) opinion articles, (9) experimental studies. Exclusion criteria were: (1) non-human subjects, (2) non-English, (3) outside of the specified timeframe, (4) articles on male healthcare. The results of the literature review were synthesised into public health models of care: (1) primary care; (2) hospital-based and inter-conception care; (3) specific preconception care clinics; and, (4) community outreach. Fifteen evaluations of preconception care were identified. Community programmes demonstrated a significant impact on substance use, folic acid supplementation, diabetes optimization, and hyperphenylalaninemia. An ideal preconception visits entail risk screening, education, and intervention if indicated. Subsequently, four public health models were developed synthesizing preconception care delivery at a population level. Heterogeneity of risk factors, health systems and strategies of care reflect the lack of consensus about the best way to deliver preconception care. The proposed models aim to reflect differing aspects of preconception healthcare delivery. PMID- 24234280 TI - Precocious puberty and age estimation: a medico-legal case report. PMID- 24234281 TI - Biotechnological applications of plant cells. AB - This article has tended to stress some important biotechnological applications of plant cells, as though these lie only in the future. It should be stressed at this point that many Japanese patents already exist describing the utilization of plant cells for many of the types of applications treated in this article. A discussion of these patents, and the subjects to which they apply, can be found in ref (113).Future biotechnological applications of plant cells can conceivably follow in two directions. First, much greater utilization of plant cells using mass growth, and whole cell immobilization techniques already utilized with bacterial cells. Second, the possible creation of new types of cells by the various genetic engineering techniques that have been briefly described in this text. Such techniques may conceivably lead to the production of entirely new and novel compounds by plant cells, or alternatively, may greatly improve the utilization of substrates and the production of existing compounds by these cells. PMID- 24234282 TI - Temperature-dependent behavior of immobilized alkaline phosphatase II. temperature pulse : A tool to enhance enzymatic activity for prolonged periods. AB - The specific activity of immobilized alkaline phosphatase can be considerably increased by exposure to a brief temperature pulse. The thus-pulsed preparations show a hysteresis of higher activity at room temperature varying from 10 min to several days, depending upon their pretreatment and the conditions of the reaction mixture during the pulse. In almost all cases the pulse can be repeated many times to increase the activity. PMID- 24234283 TI - Solubilization and purification of galactosyltransferase from golgi membranes of rat ventral prostate. AB - UDP-galactose ovomucoid galactosyltransferase, a membrane-bound enzyme involved in the biosynthetic pathways for formation of the nonreducing terminal oligosaccharide sequences on glycoproteins, has been solubilized and purified from rat ventral prostate Golgi membranes.Solubilization was effected by treatment of the particulate fraction with Triton X-100 (0.5% v/v) and MnCl2 (25 mM). The solubilized enzyme was purified by affinity chromatography on hen ovomucoid-sepharose column.The purified galactosyltransferase showed three protein bands of approx. 74,000, 60,000, and 54,000 daltons on sodium dodecyl sulfate gel electrophoresis. On gel filtration, enzyme activity eluted at approx. 70,000 daltons with a broad shoulder between 60,000 and 50,000 daltons.Isoelectric focusing of the purified enzyme resolved at least five active bands with pHi of 9, 7.4, 6.75, 6.1, and 4.8. PMID- 24234284 TI - Studies on the overproduction of indole-containing metabolites by a methanol utilizing yeast : Hansenula polymorpha. AB - Production of indole-containing metabolites ("indoles") from methanol has been studied using a mutant ofHansenula polymorpha resistant to 5-fluorotryptophan. Whereas the wild-type culture produces only a small amount of indoles, the mutant is partially deregulated and overproduces indoles. Indoles production was studied in batch and continuous culture and in a washed-cell system. When the pH was above 4.0, indoles production was growth-associated, in both minimal and complex media, and batch or continuous culture. When the pH was below or equal to 4.0, a low phosphate concentration was found to improve production. In a phosphate deficient washed-cell suspension system, the addition of an amino acid such as methionine at 5 mM increased specific productivity by more than 60%. Addition of cycloheximide at 50 mg/L decreased residual growth and increased maximum productivity of indoles by more than 60%. When the antibiotic was added at 1000 mg/L, growth was completely inhibited and indoles production continued for about 35 h. PMID- 24234285 TI - Sepharose-immobilized triazine dyes as adsorbants for human lymphoblastoid interferon purification. AB - An extensive selection of immobilized triazine dyes have been examined for their potential as adsorbants for human lymphobalstoid interferon. Procion red HE7B was selected as the most suitable for preparative scale purification. Sepharose immobilized procion red HE7B is able to bind 10(5) reference units/mL of interferon from cell supernatants and can be eluted with at least 25-fold purification and 90% yield by a KC1 gradient. Further purification was obtained either by reapplying the eluted interferon after dialysis to the dye column or by gel filtration on Ultrogel AcA 34 after lyophilization and dialysis. The latter procedure gave a final activity of about 10(6) U/mg protein and approximately 75% recovery of interferon activity. PMID- 24234286 TI - Rapid determination of anti-enzyme titer in serum using wholeStaphylococcus aureus cells. AB - Heat-killed, formalin-fixedStaphyloccous aureus (Cowan) cells are shown to be an excellent immunoadsorbent for quickly and accurately measuring the titer of antibodies directed against enzymes. The simple procedure is illustrated by following the course of immunization of a rabbit against mouse uridine 5't monophosphate synthase. The antibody titer of a serum sample can be determined in roughly 1 h plus the time to perform the assays of enzyme (antigen) activity. PMID- 24234288 TI - [The STEPWISE database--what can we learn from a Swedish quality registry for eating disorders?]. AB - National quality registries aim at improving health care. Sweden has experience in this area for over 30 years, and to date there are 73 official national registries in use within certain specialties. To our knowledge, Sweden is the only country using a web-based national quality registry (RIKSAT) that systematically documents eating disorder treatment and outcome. RIKSAT is part of a progressively growing web-based database (STEPWISE), which can help to bridge the gap between clinical work, quality registry and research. In this article, we present methods and contents of the STEPWISE system and critically discuss its potential and challenges. We establish a relation to registries within the German health care system and the preparatory work for a German web-based registry for eating disorders. PMID- 24234287 TI - Effect of nursing home ownership on hospitalization of long-stay residents: an instrumental variables approach. AB - Hospitalizations among nursing home residents are frequent, expensive, and often associated with further deterioration of resident condition. The literature indicates that a substantial fraction of admissions is potentially preventable and that nonprofit nursing homes are less likely to hospitalize their residents. However, the correlation between ownership and hospitalization might reflect unobserved resident differences rather than a causal relationship. Using national minimum data set assessments linked with Medicare claims, we use a national cohort of long-stay residents who were newly admitted to nursing homes within an 18-month period spanning January 1, 2004 and June 30, 2005. After instrumenting for ownership status, we found that IV estimates of the effect of nonprofit ownership on hospitalization are at least as large as the non-instrumented effects, indicating that selection bias does not explain the observed relationship. We also found evidence suggesting the lower rate of hospitalizations among nonprofits was due to a different threshold for transfer. PMID- 24234289 TI - [Comorbid psychiatric disorders and differential diagnosis of patients with autism spectrum disorder without intellectual disability]. AB - Autism spectrum conditions (ASC) without intellectual disability are often diagnosed late in life. Little is known about co-occurring psychiatric disorders and differential diagnosis of ASC in adulthood, particularly with regard to personality disorders. What kind of comorbid psychiatric disorders occur in ASC? Which are the most prevalent differential diagnoses in a sample of patients who seek autism specific clinical diagnostics? 118 adults who were referred with a presumed diagnosis of autistic disorder, were diagnosed with autism specific instruments and the prevalence of further psychiatric disorders was investigated. 59 (50%) fulfilled the criteria of ASC. 36% of the individuals with ASC fulfilled also criteria for a DSM-IV axis-I psychiatric disorder. Affective disorders (24%) and social phobia (14%) were the most prevalent comorbid disorders. The most frequent differential diagnoses were depression, social phobia, paranoid, avoidant and narcissistic personality disorder. PMID- 24234290 TI - [Self-selection processes in the choice of the therapeutic training approach: differences in therapeutic attitudes, personality traits and attributional complexity]. AB - AIM: Treatment approaches differ to a great extent in terms of basic psychological assumptions and practical procedures. This creates questions about the fitting of therapist and therapeutic approach. This paper examines the influence of therapeutic attitudes, mentalization interest and personality traits on the decision for an approach. METHODS: 184 participants of training programs in one of the 3 licensed treatment approaches in Germany were examined with questionnaires at the beginning of their training. RESULTS: Participants significantly differed in terms of therapeutic attitudes and the metallization interest but not in personality traits except openness. Satisfaction with training was not related to the individual fit of participants to the therapeutic attitudes typical for their approach. CONCLUSION: Therapeutic attitudes, the extent of mentalization interest, and openness may play a role in self-selection processes in the choice of the approach. PMID- 24234291 TI - Gamblers. PMID- 24234292 TI - Surfactant solubilization of hydrophobic compounds in soil and water : I. Dodecylsulphate monomer and micellar partition coefficients for 28 polychlorinated biphenyls (PCBs) [41]. AB - Reductions in the apparent soil-water partition coefficients (Kd (*)) for 28 polychlorinated biphenyls (PCBs) caused by the surfactant sodium dodecylsulphate (SDS) in the aqueous phase were studied. Above the critical micelle concentration (CMC) of the surfactant, Kd (*) was reduced by 2-3 orders of magnitude, but even far below CMC at environmentally relevant surfactant concentrations significant reductions in Kd (*) were observed. The plot of the soil-water partition coefficient (Kd) divided by Kd (*) versus the concentration of SDS allowed for the calculation of monomer (Kmn (oc)) and micellar (Kmc (oc)) surfactant-water partition coefficients normalized to organic carbon for each PCB congener. Kmn (oc) values were comparable with published values for the partition of PCBs between natural dissolved organic matter and lake water. Kmc (oc) values were up to 30 times higher than Kmn (oc) values and comparable with published octanol water distribution coefficients. The findings of the present study underline the potential of surfactants at concentrations below their CMC to mobilize otherwise strongly bound hydrophobic compounds in soil-water systems. PMID- 24234293 TI - Determination of microbial activity in activated sewage sludge by dimethyl sulphoxide reduction : Evaluation of method and application. AB - A method was developed to determine the dimethyl sulphoxide (DMSO) reduction rate in activated sewage sludge at nearly natural conditions.Linearity of microbially produced dimethyl sulphide with incubation time and sample size was shown. Apart from a fast, sensitive and highly reproducible automatic analysis of dimethyl sulphide, simultaneous determination of mineralisation, respiration and phenol degradation rates was possible.The DMSO reduction rate of samples taken from a municipal sewage plant ranged between 2 and 3 MUmol/(g dry matter . h), respiration and mineralisation rates between 30 and 80 MUmol/(g . h). Added(13)C6 phenol was completely degradated after 96 h of incubation. A half-life of 14 h was calculated assuming first order decay. Dose response curves were obtained by incubating samples for 2, 6, 25, and 96 hours after addition of pentachlorophenol. At an incubation time of 6 h, the EC50 values ranged from 20 mg/L (DMSO reduction) to 30 mg/L (phenol degradation) up to 180 mg/L (respiration and mineralisation). Increasing the incubation time to 96 h resulted in a lower EC50 of 9 mg/L for DMSO reduction, whereas it increased to 500 mg/L for respiration and mineralisation. PMID- 24234294 TI - Deposition of semivolatile organic compounds to spruce needles : I. Calculation of dry and wet fluxes. AB - The deposition of atmospheric tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene, alpha-HCH, gamma-HCH, DDT, DDE and the PCB congeners 52, 101, 138, 153 and 180 to spruce needles (Picea abies) was estimated for a period of 9 months. Accumulation in spruce as a result of dry gaseous deposition, particle bound deposition and wet deposition was calculated on the basis of the corresponding deposition rates and the compounds' concentrations in the different atmospheric compartments. The comparison of the calculated values with the concentrations of the compounds measured in 9-month-old spruce needles showed that for many compounds each deposition pathway could explain a large part of the concentrations found in the needles. PMID- 24234295 TI - Simulation of pesticide runoff at Rosemaund Farm (UK) using the SoilFug model. AB - A validation exercise of the SoilFug model using field runoff data from Rosemaund Farm (UK) is described. A comparison has been made of modelled and measured concentrations of several pesticides in surface water and soil during and after specific rain events following application. The field experiments were designed to obtain data on rainfall, outflows of water, pesticide application rates and concentrations in soil and water. The results were satisfactory for the undissociated pesticides (atrazine, carbofuran, dimethoate, isoproturon, lindane, simazine and trifluralin), whose concentrations in water were mostly predicted within an order of magnitude of measured data. The results for the dissociated pesticides (dichlorprop, MCPA, mecoprop) were less satisfactory, giving generally much higher predicted concentrations in water. The use of the SoilFug model is suggested for the calculation of predicted environmental concentrations (PECs) in water, since it generally produces acceptable results from a relatively small set of input data, most of which is generally available. PMID- 24234296 TI - Ancient atmosphere- Validity of ice records. PMID- 24234298 TI - Joint Global Ocean Flux Study (JGOFS). PMID- 24234297 TI - Observations on long-term air-soil exchange of organic contaminants. AB - Evidence for long-term changes in the soil composition of selected organic compounds, brought about by exchanges with the atmosphere, is briefly reviewed. In the case of some compounds - such as benzo(a)pyrene and octachlorodibenzo-p dioxin, soils may be significant long-term environmental sinks for atmospherically-derived material. In other cases - such as phenanthrene and some of the lighter PCBs, de-gassing or volatilisation from soil back to the air can occur under certain conditions. Hence the soil may act as a "short-term" sink, and a potential source to atmosphere. Indeed, for some 'semi-volatile' compounds used in large quantities in the past - such as PCBs, soil outgassing may actually be an extremely important source to contemporary air. Furthermore, soil outgassing from areas of former high use may provide an important driving mechanism for continued "global cycling" of a range of semi-volatile organochlorine compounds. PMID- 24234299 TI - From pollutants to industries. PMID- 24234300 TI - European Environment Agency (EEA). PMID- 24234301 TI - Life Cycle Assessment - ISO/TC 207/subcommittee 5. PMID- 24234302 TI - Environmental hazard - Assessment of chemicals and products : Part III: The limits to single compound assessment. AB - Part III: The Limits to Single Compound AssessmentThe principles and basic assumptions of single compound assessment are briefly reviewed. Limitations to this approach are shown, especially with regard to complex mixtures of similar substances, substitution products, and complicated (final) products containing chemicals and materials produced by the chemical industry. A new thinking in product lines and life cycles is emerging, leading to new assessment methods. In some cases, substitution has not improved the environmental performance of products, since very similar chemicals were used as substitutes. PMID- 24234303 TI - Microbiological remediation of waste-oil polluted soils : Ecotoxicological and toxicological considerations. AB - A waste-oil contaminated site situated near a river is supposed to be cleaned-up by means of different but complementary methods. On the basis of a research project, target values have been developed in close cooperation between the participant parties for the saturated and the unsaturated soil layers.The clean up targets are introduced and discussed. PMID- 24234304 TI - Conference Report Fourth SETAC Europe Meeting Brussels, April 11-14, 1994. PMID- 24234306 TI - Retroperitoneal hemorrhage from kidney angiomyolipoma. PMID- 24234307 TI - CF carrier testing: Experience of relatives. AB - Consensus exists that genetic counseling and CF carrier testing should be offered to individuals with a positive family history of CF. To learn more about their experience with genetic counseling and testing we conducted a series of structured telephone interviews and focus group discussions with individuals and couples who had undergone genetic counseling and carrier testing because of a family history of CF. Traditional genetic counseling appears to have been effective for this population. Subjects generally report having a positive counseling experience and few difficulties upon learning their carrier status. Subjects were quite knowledgeable about CF and their carrier risk and were highly motivated to seek testing. They may not be representative of all individuals with a family history of CF however. For carriers, concerns about whether and when to have children tested, and concerns about insurance implications of carrier status may emerge sometime after the initial counseling. Strategies for addressing these concerns and for providing efficient and effective education and genetic counseling for people with a family history of CF need to be developed. PMID- 24234308 TI - A comparison of two approaches to education about carrier testing for cystic fibrosis. AB - We tested the efficacy of two types of educational materials for genetic counseling: a traditional information brochure and one adding a role model story. Brochures were alternated weekly at a prenatal genetics center. Subjects were asked to read the brochure and fill out a questionnaire covering demographics and variables from the health belief model (impact, barriers, motivation, susceptibility, knowledge, severity). A group of 409 pregnant women and 251 male partners participated. Study design was quasiexperimental, using a post-test only comparison group. The brochure with modeling enhanced the perception of both risk and the severity of the disease and was inversely associated with the assessment of barriers, but did not directly impact on the decision to pursue testing; only 12% chose to be tested, with no significant differences between groups. While suggestive, the study is not confirmatory and should be repeated with a more heterogenous group of women. PMID- 24234309 TI - Genetic counseling for the next 25 years: Models for the future. AB - Currently, two trends pose particular challenges for genetic counseling: (1) spin offs from the Human Genome Project leading to new diagnostic genetic tests far in advance of any cures; and (2) an increasing and diversified client population. These trends will lead to changes in both genetic service delivery systems and the development of alternative models of the genetic counseling process itself. Two models that could be adapted for genetic counseling are: the mutual participation model and the life history narrative model. Technological advances present ethical dilemmas and raise many questions. Already, improved detection of genes for predisposing conditions has entered clinical medicine requiring renewed ethical appraisals of genetic testing. Integration of genetic counseling (and required pre-screening education) into primary care settings involves time constraints and the involvement of health care personnel with less training in genetics. Alternative approaches are beginning to be discussed. Innovative genetic counselors with expanded visions of counseling goals and practices will play an increasingly important role in the future of genetic counseling. PMID- 24234310 TI - Embryo genetic disorder analysis demonstration project: A model protocol. AB - A demonstration project designed for couples at a minimum 25% risk for having a child with cystic fibrosis is being undertaken using embryo genetic disorder analysis within an organization proficient inin vitro fertilization techniques. Prior to offering the project to patients, issues were identified that needed to be addressed in order to improve the likelihood of success. We then developed a set of protocols that would enable us to introduce this new technology to our staff and to prospective patients in a consistent manner. PMID- 24234311 TI - Introduction and overview. PMID- 24234312 TI - Salivary proline-rich proteins in mammals: Roles in oral homeostasis and counteracting dietary tannin. AB - We review information on the structure of proline-rich proteins (PRPs), their various functions related to oral homeostasis and dietary tannin, and the structural basis of these functions. Consideration of the multifunctional nature of these salivary proteins helps explain both the subtle and large variations found in structure and secretion rates both within individuals and between species. We propose that the ancestral function of PRPs is in maintaining oral homeostasis and that counteracting dietary tannins by binding with them is a derived function. PRPs are effective in oral homeostasis at low secretion levels, whereas counteracting tannin depends on high secretion levels. In the dietary habits ranging from carnivores through omnivores to exclusively planteaters, the dietary nitrogen level is progressively reduced, and plant allelochemical intake, including tannins, increases. We suggest that during this evolution from meat eater to plant-eater, there was some point in omnivory at which selective pressure from nitrogen limitations, arising from a low nitrogen/high tannin diet, became sufficiently great for the evolution of increased secretion level and diversification of PRPs for dealing with tannin. If this hypothesis is correct, carnivorous mammals should secrete low levels of PRPs for oral homeostasis, but should never secrete high levels, unless they are secondarily carnivorous. Omnivores consuming a diet of very little animal tissue but higher levels of tannin-containing foliage or fruit should generally have the capacity to produce high levels of salivary PRPs. Browsers and frugivores should also produce high levels of PRPs, but grazers may have reduced secretion rates depending on the antiquity of the dietary habit. This hypothesis is consistent with the limited information available on the abundance, type, and distribution of PRPs in mammals. Studies are suggested which would test the functional and evolutionary arguments presented. PMID- 24234313 TI - Modeling metabolic costs of allelochemical ingestion by foraging herbivores. AB - A mathematical model of intermediary metabolism of allelochemicals by vertebrate herbivores is presented and used to quantify the metabolic costs of detoxification. Conjugation with glucuronic acid and maintenance of acid-base status causes catabolism of amino acid and is shown to result in loss of body protein and depletion of glucose. An interaction between allelochemical dose and nutrient status is found, and the ratio of allelochemical to nutrient absorption rate defines the tolerance of the animal to absorbable allelochemical concentration in foods. The interaction is nonlinear and the ecological implications of this for foraging behavior and diet choice are discussed. PMID- 24234314 TI - Consequences of biotransformation of plant secondary metabolites on acid-base metabolism in mammals-A final common pathway? AB - Regulation of acid-base homeostasis is essential for mammals and birds. Biotransformation and metabolism of absorbed plant secondary metabolites (PSMs) results in the production of organic acids that threaten acid-base homeostasis. Consequently these acids must be buffered and excreted from the body. The production of an acid load from detoxified PSMs should occur in herbivorous mammals and birds and with most PSMs and so may provide a unifying theme to explain many effects of PSMs on animal metabolism. Since the organic acids will be largely ionized at physiological pH, disposal of the hydrogen ion and the organic anion may proceed independently. Most hydrogen ions (H(+)) from organic acids are eliminated by one or more of three ways: (1) when they react with bicarbonate in the extracellular fluid to form carbon dioxide and the carbon dioxide is exhaled, (2) when they bind to dibasic phosphate and are excreted by the kidney as monobasic phosphate, and (3) when they are buffered and retained in the skeletal system. The secretion of phosphate ions and ammonium excretion are two ways in which the kidney replaces bicarbonate ions that have been eliminated as carbon dioxide. Secretion in the kidney tubule is an important means of excreting excessive organic anions rapidly. This process is saturable and may be subject to competition from a variety of different metabolites. Lagomorphs have limited capacity to form new bicarbonate from ammonium excretion and may therefore be obliged to excrete other cations such as sodium to balance the excretion of organic anions from PSMs. Acidemia has wide-ranging impacts on animals but browsing mammals and birds may have to break down muscle tissues to provide for urinary ammonium in order to generate bicarbonate for buffering. Acidemia also can affect the extent of urea recycling. Animals consuming browse diets may have to regulate feeding so that the rate of formation of hydrogen ions does not exceed the rate of disposal. The mechanisms by which this could occur are unknown. PMID- 24234315 TI - A temperature-dependent model for predicting release rates of pheromone from a polyethylene tubing dispenser. AB - A model was developed to describe release of two formulations of tetradecenyl acetates in Shin Etsu polyethylene tubing pheromone dispensers. Change in pheromone column length in the polyethylene tubing was modeled bydl/dt=l ... (a+bT)/dt (wherel is column length,t is time interval, andT is average temperature for that time interval). Regression of the natural log of relative change in liquid length against time interval and accumulated day degrees in orchards produced the coefficientsa andb. The model was validated by comparing predicted and actual liquid length remaining in field-aged dispensers, as well as measuring release rates by using gas chromatography. Mean daily orchard temperatures and measurement of column length of dispensers on a single date were used to accurately predict column length within 15%, after six months. Predictions of instantaneous release rate were also made from this model, and other possible model uses and limitations are discussed. PMID- 24234316 TI - Development of a bioassay to test phloem sap samples from lettuce for resistance toNasonovia ribisnigri (homoptera, aphididae). AB - TheNr-gene-based resistance of lettuce to the aphidNasonovia ribisnigri (Mosley) has previously been shown to be located in the phloem. Since chemical analyses of the phloem sap had shown no differences between resistant and susceptible lines, a bioassay was developed in order to test samples from resistant and susceptible plants on aphid feeding. For this, whole-plant extracts, honeydew, and EDTA collected phloem extracts were obtained, and a sensitive bioassay was developed using EDTA samples. The EDTA was removed, and samples were added to a simple sucrose solution or to a complex artificial diet and presented in a choice situation comparing extracts from resistant and susceptible plants. EDTA collected phloem sap samples from susceptible plants were preferred to those from resistant plants. The resistance is probably based on a feeding deterrent activity of the phloem sap in the resistant plant. PMID- 24234317 TI - A chemical basis for differential allelopathic potential of sorghum hybrids on wheat. AB - The basis for differential allelopathic potentials among sorghum (Sorghum bicolor L. Moench) hybrids was investigated by conducting quantitative and qualitative studies of their phenolic contents. Total phenolic content in sorghum plant parts varied within hybrids, among hybrids, and between growing seasons. Inhibition of wheat (Triticum aestivum L.) radicle growth was positively associated (r=0.66) with concentrations of total phenolics contained in plant parts. Extracts from culms contributed the higherst proportion of toxicity from sorghum plants, inhibiting radicle growth up to 74.7%. Concentrations of five phenolic acids,p hydroxybenzoic (POH), vanillic (VAN), syringic (SYR),p-coumaric (PCO), and ferulic (FER), differed in all plant parts of the three sorghum hybrids. Concentrations of POH, VAN, and SYR were consistently higher than PCO and FER. PCO and FER wer absent from some plant parts, with FER being the most frequently missing. Inhibition of wheat radicle growth was found to be positively associated with the concentration of each phenolic acid. Vanillic acid was most highly associated (r=0.44) with inhition. Thus, above-ground sorghum tissues contained phenolic acids that contributed to allelopathic potential. Additionally, sorghum roots exuded POH, VAN, and SYR that may enhance the overall allelopathic potential of sorghum during growth and after harvest when residues remain on the soil surface or are incorporated prior to planting a subsquent crop. PMID- 24234318 TI - Production and release of (Z,E)-9,12-tetradecadienal by sex pheromone glands of females ofPlodia interpunctella (lepidoptera: pyralidae). AB - Extracts of sex pheromone glands obtained from females ofPloida interpunctella contained detectable amounts of (Z,E,)-9,12-tetradecadien-1-ol acetate (Z9,E12 14:Ac) and (Z,E.)-9,12-tetradecadien-1-ol (Z9,E12-14:OH) 4 hr prior to the first scotophase after adult emergence. The amount of pheromone increased during the first 4 hr of the scotophase and then declined to low levels during the subsequent photophase. Decapitation of females immediately after emergence, prior to expansion of the wings, inhibited production of pheromone during the subsequent 48 hr. Injection of extracts of the heads of 1-day-old females ofP. interpunctella of partially purified extracts of the cephalic ganglia of females of the corn earworm moth into decapitated females stimulated production of bothZ9,E12-14:Ac andZ9,E12-14:OH as well as production of (Z,E)-9,12 tetradecadienal (Z9,E12-14:Al). This aldehyde was subsequently identified from extracts of pheromone glands obtained from naturally calling females as well as from volatiles emitted by calling females. Studies on the terminal steps in biosynthesis of the pheromone showed thatZ9,E12-14:OH was produced from the corresponding acetate and thatZ9,E12-14:Al was produced from the alcohol via the action of an oxidase(s). PMID- 24234319 TI - Insecticidal defenses of Piperaceae from the neotropics. AB - Insecticidal and growth-reducing properties of extracts of 14 species of American neotropical Piperaceae were investigated by inclusion in diets of a polyphagous lepidopteran, the European corn borer,Ostrinia nubilalis. Nutritional indices suggested most extracts acted by postdigestive toxicity.Piper aduncum, P. tuberculatum, andP. decurrens were among the most active species and were subjected to bioassay-guided isolation of the active components. Dillapiol was isolated from the active fraction ofP. aduncum, piperlonguminine was isolated fromP. tuberculatum, and a novel neolignan fromP. decurrens. The results support other studies on Asian and AfricanPiper species, which suggest that lignans and isobutyl amides are the active defence compounds in this family. PMID- 24234320 TI - Alkyl ether and enol ether analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth,Agrotis segetum: probing a proposed bioactive conformation for chain-elongated analogs. AB - In order to test a previous conclusion that chain-elongated analogs of (Z)-5 decenyl acetate(1), a pheromone component of the turnip moth,Agrotis segetum, adopt a loop conformation of the terminal alkyl chain in the bioactive conformation, a series of alkyl ether and enol ether analogs of1 and (Z)-5 dodecenyl acetate(2) have been synthesized and tested using singlecell electrophysiology. In these analogs a methylene group in positions 7 and 9 of1 and in positions 7 and 11 in2 have been replaced by an oxygen atom in order to energetically facilitate the formation of a loop conformation in the chain elongated analogs. The electrophysiological results in combination with molecular mechanics (MM2 and MM3) calculated conformational energies show that the activity decreases of the chain-elongated ether analogs are significantly smaller than that for2 and that these activity decreases parallel the conformational energies for a loop formation of the terminal chains in the analogs. The results support our previous conclusion that the terminal chain of chain-elongated analogs of1 adopts a loop conformation in their bioactive conformations. PMID- 24234321 TI - Mechanism by which noninhibitory concentrations of glucose increase inhibitory activity ofp-coumaric acid on morning-glory seedling biomass accumulation. AB - Noninhibitory levels of glucose-C [<= 72 ug carbon (C)/g soil] increased the inhibitory activity ofp-coumaric acid on morning-glory seedling biomass accumulation in Cecil Bt-horizon soil. The amount ofp-coumaric acid required for a given level of inhibition of shoot and seedling biomass accumulation decreased as the concentration of glucose increased. Soil extractions with neutral EDTA (0.25 M, pH 7) after addition of combinations ofp-coumaric acid and glucose (concentrations ranging from 0 to 1.25 umol/g soil) to the soil showed that utilization ofp-coumaric acid by microbes decreased linearly as the concentration of glucose increased. The increased inhibitory activity of a given concentration ofp-coumaric acid in the presence of glucose was not due to a reduction in soil sorption ofp-coumaric acid or effects of nitrogen-limited microbial growth. Noninhibitory levels of phenylalanine andp-hydroxybenzoic acid slowed the utilization ofp-coumaric acid by microbes in a similar manner as glucose. The presence of methionine, however, did not affect the rate ofp-coumaric acid utilization by microbes. These observations suggest that differential utilization of individual molecules in organic mixtures by soil microbes can modify, and in this case increase, the effectiveness of a given concentration of an inhibitor such asp-coumaric acid on the inhibition of seedling growth such as morning glory. PMID- 24234322 TI - Chirality of israeli pine bast scale,Matsucoccus josephi (homoptera: Matsucoccidae) sex pheromone. AB - The absolute configuration of the sex pheromone of the Israeli pine bast scale,Matsucoccus josephi, was determined as (2E,5R,6E,8E)-5,7-dimethyl-2,6,8 decatrien-4-one, designated here asR-E with 10% (2E,5S,6E,8E)-5,7-dimethyl-2,6,8 decatrien-4-one, designated asS-E. The chirality of the quantitatively minorZ isomer was (2E,5R,6Z,8E)-5,7-dimethyl-2,6,8-decatrien-4-one (R-Z). Chiral assignments were made by comparative gas chromatographic (GC) analysis of naturalM. josephi pheromone with stereoselectively synthesized stereoisomers on a chiral Cyclodex-B column, which separated the enantiomers with baseline resolution. In gas chromatographic-electroantennographic detection (GC-EAD) analysis of the racemicZ andE isomers, the latter elicited the stronger antennal response by maleM. josephi. In GC-EAD of all four stereoisomers, employing the chiral column,R-E was the most active stereoisomer. In field testsR-E attracted 10 times more males ofM. josephi than didS-E. The racemicE/Z pheromone mixture, containing all four stereoisomers in approximately equal amounts, attracted as many maleM. josephi as did an equivalent amount ofR-E, indicating that the other stereoisomers are not inhibitory. The same keto-diene moiety with the same chiral center and configuration in all three known Matsucoccidae sex pheromones implies a common biosynthetic pathway and phylogenetic relationship. PMID- 24234323 TI - Chemical nature of larval osmeterial secretions of papilionid butterflies in the generaParnassius, Sericinus andPachliopta. AB - Volatile components of the larval osmeterial secretion ofParnassius glacialis (Parnassiinae, Parnassiini) consisted of isobutyric acid, 2-methylbutyric acid, and their methyl esters. In contrast, the osmeterial exudate ofSericinus montela (Parnassiinae, Zerynthiini) was characterized as monoterpene hydrocarbons comprisingbeta-myrcene (Major),alpha-pinene, sabinene, limonene, andbeta phellandrene, whereas that ofPachliopta aristolochiae (Papilioninae, Troidini) was composed of numerous sesquiterpene hydrocarbons, includingalpha himachalene,alpha-amorphene, and germacrene-A, and a few oxygenated sesquiterpenoids. In these three species, the chemical nature of the secretions of the last and the penultimate instars was essentially of similar quality, suggesting that the three genera,Parnassius, Sericinus, andPachliopta, are assigned to homogeneous types. PMID- 24234324 TI - Putative chemical signals from white-tailed deer (Odocoileus virginianus). Urinary and vaginal mucus volatiles excreted by females during breeding season. AB - Urine and vaginal mucus samples from female white-tailed deer in estrus and mid cycle were analyzed by combined gas chromatography-mass spectrometry (GC-MS). Forty-four volatiles were found in mucus and 63 in urine. The volatiles common to both vaginal mucus and urine included alcohols, aldehydes, furans, ketones, alkanes, and alkenes. Aromatic hydrocarbons were present only in the vaginal mucus, whereas pyrans, amines, esters, and phenols were found only in urine. Both estrous mucus and estrous urine could be identified by the presence of specific compounds not present in mid-cycle samples. Numerous compounds exhibited dependency on ovarian hormones. PMID- 24234326 TI - Effects of work-oriented fitness courses in lumberjacks with low back pain. AB - This prospective controlled study examined changes in fitness, health, and work ability after a work-oriented physical fitness course arranged for lumberjacks experiencing low back pain but being still at work. The 1-week courses were designed to activate exercising during leisure time and consisted of fitness tests, various types of exercise, and lectures. Eighty-seven lumberjacks participated in the courses and 61 subjects served as controls. Questionnaire data obtained before and 1 year after the course were available for 78 (90%) of the course participants and 41 (67%) of the controls. In the intervention group, perceived fitness, health, and work ability improved and ergonomic strain at work decreased. Both groups reported an increased frequency of leisure-time physical activity. There were between- group differences in the development of fitness, health, distress symptoms, and subjective work ability, whereas the changes in physical activity, back and musculoskeletal symptoms, or ergonomic strain did not differ between the groups. In a 6-month follow up, muscle function improved in the intervention group, but no change was observed in aerobic capacity. There was a tendency of the number of back pain-related sickness leaves, but not of their duration, to develop more favorably in the intervention group, when data from the year before and the year after the course were compared. PMID- 24234327 TI - Effectiveness of workplace accommodations for a corporate telephone operator with a full left-arm prosthesis: A case study. AB - A corporate telephone operator and voice mail programmer was involved in a serious automobile accident resulting in left-arm amputation and through rehabilitation received a full left-arm prosthesis. Upon returning to work in her previous job capacity, some work activities and work area configurations were identified as problematic during task performance. Work methods and work area configuration were evaluated regarding their appropriateness for supporting return to work and long-term accommodation. Job activity analysis determined all reaches, clearances, and forces and their compliance with recommended criteria. A body part comfort/discomfort survey (BPCDS) was administered pre- and post accommodation to elicit information regarding workplace problem areas and provide a measure to assess accommodation effectiveness. Workstation, support equipment, work area, seating, task assignments, and work methods were modified to more appropriately support operator task performance. Comparison of pre- and post accommodation BPCDS indicates a significant reduction in operator discomfort with residual discomfort associated with the orthopedic prosthesis. This case study illustrates the use of the principles and techniques of industrial ergonomics to develop workplace accommodations. The area of ergonomics, medical ergonomics,is an example of the development of reasonable accommodations for physically challenged workers in the spirit of compliance with the Americans with Disabilities Act (ADA). PMID- 24234325 TI - Lupus nephritis: review of the literature. AB - Physicians in practice should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE) and lupus nephritis. These disorders can present to the clinician's clinic and private office regardless of their specialty. This review will discuss various aspects of SLE, its mechanisms of disease, role of accelerated atherosclerosis, proinflammatory cytokines, and therapeutic approaches. The role of vascular endothelial growth factor in which and plasma levels have been associated with disease activity, classification of severity, and diagnosis of lupus nephritis is addressed. Current treatment options, prognosis, and future therapeutic approaches and common side effects are also discussed. PMID- 24234328 TI - Organizational socialization of employees with disabilities: Critical issues and implications for workplace interventions. AB - Organizational socialization is the process whereby newcomers to work organizations become insiders. The socialization process has been linked to various outcomes including newcomer job satisfaction, organizational commitment, job knowledge and performance, promotion and advancement rate, salary, and turnover. The purpose of the present paper is threefold: (1) to examine issues facing persons with disabilities during organizational socialization in order to help guide future research on this topic; (2) to provide an awareness of potential aditional barriers (unrealistic newcomer expectations, interaction avoidance, "norm to be kind," low work group expectations) that face newcomers with disabilities as they begin jobs; and (3) to suggest some possible policies, programs, and interventions that might help persons with disabilities to overcome those barriers. PMID- 24234329 TI - Meaningful work: Questions for vocational rehabilitation and a call for action. AB - Experiences in different cultures may lead astute observers to question existing schemes and ways of life, often taken for granted. The arena and nature of work, for instance, may differ radically from one society to another. Based on a lengthy visit to Tanna, Vanuatu, the author found that the indigenous people had qualitatively different concepts of work. Using the ideas gained from cross cultural opportunity, questions can and should be raised about the meaningfulness of work activities, vocational rehabilitation, and the importance of examining assumptions as to what constitutes meaningful work. PMID- 24234330 TI - Worklessness and disability: Expansion of the biopsychosocial perspective. AB - This paper summarizes a novel conceptualization of the biopsychosocial processes that may characterize the injured worker's reaction to separation from the workplace following injury/illness. The hypotheses are based upon clinical observation and may, in the future, be supported by controlled experimental research. Protracted worklessness is not equivalent to lost time. Worklessness is a dynamic process producing psychological, occupational, social and iatrogenic problems that accelerate the development of long term disability. The occupational physician (as well as those involved in occupational restoration and rehabilitation) is in a unique position to monitor, assess, and ultimately prevent disability. An appreciation of the dynamics of worklessness, one predicated on understanding and expanding the current biopsychosocial occupational model, will facilitate meaningful therapeutic recommendations for the injured worker. Worklessness is conceptualized as a dynamic process involving three fundamental changes: the development of anxiety separation from the workplace, the erosion of skills and loss of opportunity occasioned by absenteeism and the propensity toward the medicalization of disabilities. PMID- 24234331 TI - Serum carbohydrate antigen 19-9 and prognosis of patients with gastric cancer. AB - Previous studies have assessed the prognostic role of serum carbohydrate antigen 19-9 (CA 19-9) concentration in patients with gastric cancer, but the findings from those studies were inconsistent. We searched the PubMed and Web of Science databases to find eligible studies assessing the prognostic role of CA 19-9 in patients with gastric cancer. Twelve studies with a total of 5,072 gastric cancer patients were finally included into the meta-analysis. The pooled hazard ratio (HR) with corresponding 95 % confidence interval (95 % CI) for overall survival were calculated to assess the prognostic role of CA 19-9 in patients with gastric cancer. Overall, elevated serum concentration of CA 19-9 (>37 U/mL) was associated with poorer overall survival in patients with gastric cancer (fixed effects HR = 1.36, 95 % CI 1.24-1.48, P < 0.001). Subgroup analysis by study design further showed that elevated serum concentration of CA 19-9 was associated with poorer overall survival in patients with gastric cancer. There was no obvious risk of publication bias. Elevated concentration of serum CA 19-9 is associated with poorer overall survival in patients with gastric cancer. PMID- 24234332 TI - High expression of Cdc25B and low expression of 14-3-3sigma is associated with the development and poor prognosis in urothelial carcinoma of bladder. AB - Cdc25 dual-specicity phosphatases are essential regulators at critical stages of cell cycle. Cdc25B is overexpressed in several human tumor types. The activity of Cdc25B is regulated by 14-3-3 dimer. To investigate the roles of Cdc25B and 14-3 3sigma in bladder carcinoma, we examined expressions of Cdc25B and 14-3-3sigma proteins in bladder carcinoma and cell lines and analyzed their roles in the development and prognosis of urinary bladder carcinoma. Immunohistochmistry was used to detect the expressions of Cdc25B and 14-3-3sigma in 105 bladder carcinomas. Moreover, expressions of Cdc25B and 14-3-3sigma were analyzed by real time PCR and Western blot in 40 bladder carcinomas and 20 normal epithelial tissues. Specific siRNA was used to knockdown the expression of Cdc25B or 14-3 3sigma. Wild-type plasmid was used to overexpress 14-3-3sigma. MTT assay and Flow cytometry were used to examine proliferation and cell cycle of bladder cancer cells. There were higher Cdc25B expression and lower 14-3-3sigma expression in carcinomas than in the adjacent normal tissues (P < 0.05), positive and negative correlations being noted with clinical stage and histopathologic grade. Cdc25B expression was positively correlated with recurrence and poor prognosis. Downregulation of Cdc25B resulted in slower growth, more G2/M cells and 14-3 3sigma increasing. However, upregulation and downregulation of 14-3-3sigma did not affect cell growth and Cdc25B expression. It showed that Cdc25B upregulation and 14-3-3sigma downregulation might promote development of bladder cancer and suggested a poor prognosis. Moreover, Cdc25B could play an important role on the bladder cancer cell proliferation and cell cycle progression and regulate expression of 14-3-3sigma. PMID- 24234333 TI - Feasibility and safety of carboplatin plus paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: a pilot study. AB - The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Between June 2007 and May 2012, all patients with a diagnosis of locally advanced cervical cancer (IB2-IIB) were eligible for this protocol. All patients have received 3 cycles of carboplatin (AUC6) and paclitaxel 175 mg/mq in neoadjuvant setting. The NACT-induced toxicity and the response to treatment were evaluated according to the World Health Organization (WHO) criteria. After NACT, all patients with complete or partial response were submitted to classical radical hysterectomy type III or C2, according to different classifications, and were submitted to four adjuvant cycles of platinum-based chemotherapy. The primary endpoints of the study were to evaluate the efficacy and feasibility of carboplatin regimen. Thirty-five patients with locally advanced cervical cancer were considered. A total of 23 patients completed 3 cycles of NACT. The overall clinical response rate after NACT was 78.3% including 43.5% (n = 10) with complete response, 34.8% (n = 8) with partial response, 17.4% (n = 4) with stable disease and 4.3% (n = 1) of those who suffered disease progression. The most common toxicity was haematologic, nausea/vomiting and neuropathy with grades 1 and 2 and occurred in 56.5, 56.5 and 17.4%, respectively. No renal toxicity was registered. Our results suggest that carboplatin is a well-tolerated drug with a response rate similar to standard cisplatin. Then, it represents, in neoadjuvant setting, a valid alternative in patients affected by locally advanced cervical cancer. PMID- 24234334 TI - Prognostic value of vascular endothelial growth factor A expression in gastric cancer: a meta-analysis. AB - Vascular endothelial growth factor A (VEGF-A) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF-A overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. Electronic databases updated to September 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF-A overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 20 studies that evaluated the correlation between VEGF-A overexpression and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (hazard ratio [HR] = 1.57; 95% confidence interval [CI], 1.30-1.84) and disease-free survival (DFS) (HR = 1.85; 95% CI, 1.39-2.32) in patients with gastric cancer. No significant heterogeneity (P = 0.487) was observed among 16 studies for OS and among 7 studies for DFS (P = 0.435). VEGF-A overexpression indicates a poor prognosis for overall survival and disease-free survival in patients with gastric cancer. PMID- 24234337 TI - Statistical power of latent growth curve models to detect quadratic growth. AB - Latent curve models (LCMs) have been used extensively to analyze longitudinal data. However, little is known about the power of LCMs to detect nonlinear trends when they are present in the data. For this study, we utilized simulated data to investigate the power of LCMs to detect the mean of the quadratic slope, Type I error rates, and rates of nonconvergence during the estimation of quadratic LCMs. Five factors were examined: the number of time points, growth magnitude, interindividual variability, sample size, and the R (2)s of the measured variables. The results showed that the empirical Type I error rates were close to the nominal value of 5 %. The empirical power to detect the mean of the quadratic slope was affected by the simulation factors. Finally, a substantial proportion of samples failed to converge under conditions of no to small variation in the quadratic factor, small sample sizes, and small R (2) of the repeated measures. In general, we recommended that quadratic LCMs be based on samples of (a) at least 250 but ideally 400, when four measurement points are available; (b) at least 100 but ideally 150, when six measurement points are available; (c) at least 50 but ideally 100, when ten measurement points are available. PMID- 24234335 TI - Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma. AB - In human glioma tumors, heme oxygenase-1 (HO-1) has been shown to be upregulated both when compared with normal brain tissues and also during oligodendroglioma progression. The cell types that express HO-1 have been shown to be mainly macrophages/microglia and T cells. However, many other reports also demonstrated that cell lines derived from glioma tumors and astrocytes express HO-1 after the occurrence of a wide variety of cell injuries and stressors. In addition, the significance of HO-1 upregulation in glioma had not, so far, been addressed. We therefore aimed at investigating the expression and significance of HO-1 in human glial tumors. For this purpose, we performed a wide screening of HO-1 expression in gliomas by using tissue microarrays containing astrocytomas, oligodendrogliomas, mixed tumors, and normal brain tissues. We subsequently correlated protein expression with patient clinicopathological data. We found differences in HO-1 positivity rates between non-malignant brain (22 %) and gliomas (54%, p = 0.01). HO-1 was expressed by tumor cells and showed cytoplasmic localization, although 19% of tumor samples also depicted nuclear staining. Importantly, a significant decrease in the overall survival time of grade II and III astrocytoma patients with HO-1 expression was observed. This result was validated at the mRNA level in a cohort of 105 samples. However, no association of HO-1 nuclear localization with patient survival was detected. In vitro experiments aimed at investigating the role of HO-1 in glioma progression showed that HO-1 modulates glioma cell proliferation, but has no effects on cellular migration. In conclusion, our results corroborate the higher frequency of HO-1 protein expression in gliomas than in normal brain, demonstrate that HO-1 is expressed by glial malignant cells, and show an association of HO-1 expression with patients' shorter survival time. PMID- 24234336 TI - Astrocyte elevated gene-1: a novel independent prognostic biomarker for metastatic ovarian tumors. AB - Astrocyte elevated gene-1 (AEG-1), a novel tumor-associated gene, was found overexpressed in many tumors. Therefore, our purpose is to estimate whether AEG-1 overexpression is a novel predictor of prognostic marker in metastatic ovarian tumors. Immunohistochemistry was used to estimate AEG-1 overexpression in metastatic ovarian tumors from 102 samples. The association between AEG-1 expression and prognosis was estimated by univariate and multivariate survival analyses with Cox regression. The log-rank test was used to identify any differences in the prognosis between the two groups. The median overall and progression-free survival rates of patients with tumors from gastrointestinal tract origin were 0.97 and 0.51 years, respectively. Similarly, survival rates of patients with tumors of breast origin were 2.68 and 1.96 years (P < 0.0001). Of 102 patients, 77 had high expression, and AEG-1 overexpression had a significant link of prognosis in metastatic ovarian patients (P < 0.01). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the tumors from gastrointestinal tract primary malignancies. It is suggested that AEG 1 overexpression might be an independent prognostic marker of metastatic ovarian tumors. PMID- 24234338 TI - A comparative investigation of seven indirect attitude measures. AB - We compared the psychometric qualities of seven indirect attitude measures across three attitude domains (race, politics, and self-esteem) with a large sample (N = 23,413). We compared the measures on internal consistency, sensitivity to known effects, relationships with indirect and direct measures of the same topic, the reliability and validity of single-category attitude measurement, their ability to detect meaningful variance among people with nonextreme attitudes, and their robustness to the exclusion of misbehaving or well-behaving participants. All seven indirect measures correlated with each other and with direct measures of the same topic. These relations were always weak for self-esteem, moderate for race, and strong for politics. This pattern suggests that some of the sources of variation in the reliability and predictive validity of the indirect measures is a function of the concepts rather than the methods. The Implicit Association Test (IAT) and Brief IAT (BIAT) showed the best overall psychometric quality, followed by the Go-No-Go association task, Single-Target IAT (ST-IAT), Affective Misattribution Procedure (AMP), Sorting Paired Features task, and Evaluative Priming. The AMP showed a steep decline in its psychometric qualities when people with extreme attitude scores were removed. Single-category attitude scores computed for the IAT and BIAT showed good relationships with other attitude measures but no evidence of discriminant validity between paired categories. The other measures, especially the AMP and ST-IAT, showed better evidence for discriminant validity. These results inform us on the validity of the measures as attitude assessments, but do not speak to the implicitness of the measured constructs. PMID- 24234339 TI - The effects of salinity, temperature and sediment on the toxicity of copper to juvenile Hediste (Nereis) diversicolor (O. F. Muller). AB - Without sediment, increasing salinity (7.3 to 29.20/00) and increasing temperature (12 to 22 degrees C) reduced the toxicity of copper to juvenile Hediste diversicolor. The LC50 values ranged from 357 MUgL(-1) in 7.30/00 to 513 MUg L(-1) in 29.20/00 at 12 degrees C and from 247 to 500 MUg L(-1) at 22 degrees C. In deionized water all the juvenile were dead in all solutions to which copper was added (100 to 600 MUg L(-1)). Dead worms were swollen and everted their pharynxs. In higher doses of copper (500 to 600 MUg L(-1)) the worms were abnormal in behaviour in all salinities (0 to 29.20/00). The ability to swim or crawl was disturbed.With sediments increasing temperature and increasing salinity increased the toxicity of copper to the worms. The LC50 values ranged from 3200 to 4100 MUg L(-1) at 22 degrees C. The response of the juvenile to copper was antagonistic to increasing temperature and salinity and synergistic to increasing salinity and increasing temperature without and with the sediment respectively. PMID- 24234340 TI - The effect of temperature and salinity on copper body-burden and copper toxicity to Hediste (Nereis) diversicolor. AB - Temperature from 12 to 22 degrees C and salinity from 30.5 to 7.60/00 increased accumulation of copper in Hediste diversicolor. Copper accumulated ranged from 85.83 to 217.14 MUg g(-1). Sediments reduced accumulation of copper under temperature-salinity combinations. Accumulated copper ranged from 90.19 to 153.26 MUg g(-1).However, mortality of the worms was not solely dependent upon copper body-burden. It ranged from 34 to 45% and from 38 to 80% in the presence of sediment. A combination of osmoregulatory and thermal stresses increased the toxic effect of copper to the worms. PMID- 24234341 TI - Comparison of mass concentrations of SO2 determined in air by two different methods. AB - Mass concentrations of sulphur dioxide were determined in parallel 24-hour samples of ambient air at a measuring site in Zagreb during a period of eight years. The methods used were the West-Gaeke's tetrachloromercurate-pararosaniline method (TCM) and the Standard British Method (SBM). Total results for the annual intervals of measuring were analyzed statistically and also discussed separately for winter and summer periods, in order to see whether they are influenced by seasonal rhythm. PMID- 24234342 TI - Choosing an appropriate soil-gas survey method. AB - Three types of soil-gas surveys were performed over the same location at an industrial facility. The surveys performed were (1) a passive technique using buried collectors, (2) an active technique in which samples were collected in the field by pumping with subsequent analysis at a field laboratory, and (3) a screening technique that employed a hand-held survey instrument. Each of the surveys had desirable features, but there was considerable variability in the quality of data obtained, cost, and ease of performance. The passive and active surveys provided excellent detection limits, but the passive technique does not provide data in real time. The active survey was also time-consuming and required an analytical chemist in the field. Neither the active nor the passive survey were able to delineate the plume of contaminated groundwater. Consequently, the results from the rapid and inexpensive reconnaissance technique provided functionally equivalent data. PMID- 24234343 TI - Organochlorine residues in New York waterfowl harvested by hunters in 1983-1984. AB - Thirteen organochlorine compounds were detected in fat and breast muscle tissues of Canada goose and five species of ducks that were shot by sportsman in New York. Residues of DDE and PCB occurred most frequently and were positively identified along with DDT, heptachlor epoxide, trans-nonachlor, and hexachlorobenzene. Compounds that were detected but not positively confirmed by mass spectrometry were dieldrin, mirex, heptachlor, chlordane, oxychlordane, and endrin. Wood duck (Aix sponsa) and Canada goose (Branta canadensis) had significantly lower levels of DDE and PCB than black duck (Anas rubripes), mallard (Anas platyrhynchos), scaup (Athya sp.), and bufflehead (Bucephala albeola). Birds collected from Long Island and the Hudson River-Lake Champlain corridor carried highest concentrations. PMID- 24234344 TI - Environmental monitoring for protected areas: Review and prospect. AB - Monitoring activities in protected areas have a long history. Internal planning and management needs early led to ecological inventories. More recently the increasing number and awareness of external threats to parks has led to a variety of monitoring programs. Efforts to use protected areas, and especially biosphere reserves, as ecological baselines, have reinforced this trend. And as protected areas are increasingly recognized to be islands with complex internal and regional interactions, holistic, systems approaches to inventory, monitoring, and assessment of their state are being developed. This paper begins by reviewing threats to parks and the origins and importance of inventory and monitoring activities. A review of resource survey methods follows. Ecosystem science and environmental monitoring are introduced as a foundation for consideration of several newer approaches to monitoring and assessing the state of natural environments. These newer approaches are stress/response frameworks, landscape ecology, ecosystem integrity, and state of the environment reporting. A final section presents some principles for monitoring the state of protected areas. Examples are drawn from experience with Canadian national parks. PMID- 24234345 TI - Aluminium contamination via assisted leaching from metallic aluminium utensils at neutral pH. AB - Fluoride ion in trace concentrations is found to leach metallic aluminium from utensils even at neutral pH, releasing aluminium hydroxide which is readily soluble in dilute acids. The levels of leaching at different F(-) concentrations are given and compared with leaching levels with equivalent concentrations of Cl( ). It is suggested that consumption of water boiled in aluminium utensils may contribute to cumulative aluminium toxicity. PMID- 24234346 TI - Oleic acid promotes adaptability against oxidative stress in 3T3-L1 cells through lipohormesis. AB - Although fatty acids are important components of biological membranes, energy sources, and signal transducers or precursors of lipid mediators, excess intake of fatty acids and their accumulation cause obesity and metabolic syndrome. Thus, fatty acid quantity is known to be an important factor for obesity-related diseases, but the effects of different types of fatty acids (i.e., fatty acid quality) on human health are not completely understood. We here focused on the relationship between fatty acid quality and oxidative stress by investigating whether resistibility to tert-butyl hydrperoxide (t-BuOOH)-induced oxidative stress in 3T3-L1 cells varied according to the fatty acid type. Among eight fatty acids (both saturated and unsaturated) tested, oleic acid (OA) exerted the most pronounced cytoprotective effects, with efficacy over a wide range of concentrations. OA treatment markedly enhanced the intracellular levels of lipid peroxidation markers, including N(epsilon)-(hexanoyl)lysine, 4-hydroxy-2-nonenal, and acrolein. The levels of these markers in OA-treated cells were decreased after t-BuOOH exposure, whereas the levels in untreated control cells were notably increased after t-BuOOH exposure. Our results suggested that unsaturated fatty acids, particularly OA, could promote an adaptive response and enhance cell tolerance through increased cellular antioxidative capacity via OA-induced mild lipid peroxidation (lipohormesis), and thus protect cells against subsequent oxidative stress-related injury. PMID- 24234348 TI - NMR assignments for the cis and trans forms of the hemolysin II C-terminal domain. AB - Pathogenic bacteria secrete pore-forming toxins (PFTs) to selectively defend against immune cells and to break through cellular barriers in the host. Understanding how PFTs attack cell membranes is not only essential for therapeutic intervention but for designing agents to deliver drugs to specific human cell subtypes, for example in anti-cancer or anti-viral therapies. Many toxins contain accessory domains that help recognize specific molecular epitopes on the membranes of target cells, including proteins, carbohydrates, and lipids. Here we report NMR assignments for the 94-residue 10 kDa C-terminal accessory domain of Bacillus cereus hemolysin II, HlyIIC, that has no known structural or functional homologues. The HlyIIC domain exists in a dynamic equilibrium due to cis/trans isomerization of its Gly86-Pro87 peptide bond. The cis and trans forms are about equally populated and are in slow exchange on the NMR timescale, giving rise to separate signals for approximately half of the residues in the domain. Assignments for the cis and trans forms were achieved with the aid of a P87M mutant that stabilizes the trans form, and separate sequential walks for the two forms in 3D NMR spectra of the wild-type HlyIIC. Based on backbone chemical shifts, the domain has a alpha1-alpha2-beta1-beta2-beta3-beta4-alpha3-beta5 order of secondary structure elements. The last strand in the trans form and in the P87M mutant is shortened near Pro87 compared to the cis form. Both cis/trans isomerization and the P87M mutation cause large chemical shift changes throughout HlyIIC, suggesting that the proline is important in stabilizing the structure of the domain. The NMR assignments pave the way for solving the structures of the multiple conformational forms of HlyIIC and establishing their mechanism of interconversion. PMID- 24234349 TI - Backbone resonance assignments of human cytosolic dNT-1 nucleotidase. AB - Cytosolic dNT-1 nucleotidase plays a key role in the homeostasis of pyrimidine deoxyribonucleotides in mammalian cells. The enzyme is responsible for the dephosphorylation of physiological substrates as well as nucleoside analogues that are used in antiviral and anticancer therapies, therefore selective inhibition of the dNT-1 nucleotidase activity may lead to an increase in efficacy of this type of therapeutic compounds. Here, we report the backbone 1H, 13C and 15N assignments for the 47 kDa dNT-1 dimer, which will be used for structural characterisation of dNT-1 complexes with small molecule inhibitors obtained through modification of pyrimidine nucleotide scaffolds or optimisation of successful binders obtained from the screening of fragment libraries. PMID- 24234350 TI - Brandy R. Matthews, MD. PMID- 24234347 TI - Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models. AB - In patients with multiple sclerosis (MS), pain is a frequent and disabling symptom. The prevalence is in the range 29-86 % depending upon the assessment protocols utilised and the definition of pain applied. Neuropathic pain that develops secondary to demyelination, neuroinflammation and axonal damage in the central nervous system is the most distressing and difficult type of pain to treat. Although dysaesthetic extremity pain, L'hermitte's sign and trigeminal neuralgia are the most common neuropathic pain conditions reported by patients with MS, research directed at gaining insight into the complex mechanisms underpinning the pathobiology of MS-associated neuropathic pain is in its relative infancy. By contrast, there is a wealth of knowledge on the neurobiology of neuropathic pain induced by peripheral nerve injury. To date, the majority of research in the MS field has used rodent models of experimental autoimmune encephalomyelitis (EAE) as these models have many clinical and neuropathological features in common with those observed in patients with MS. However, it is only relatively recently that EAE-rodents have been utilised to investigate the mechanisms contributing to the development and maintenance of MS-associated central neuropathic pain. Importantly, EAE-rodent models exhibit pro-nociceptive behaviours predominantly in the lower extremities (tail and hindlimbs) as seen clinically in patients with MS-neuropathic pain. Herein, we review research to date on the pathophysiological mechanisms underpinning MS-associated neuropathic pain as well as the pharmacological management of this condition. We also identify knowledge gaps to guide future research in this important field. PMID- 24234351 TI - Neurodegenerative dementias. PMID- 24234353 TI - Dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is a synucleinopathy that is clinically distinct from Alzheimer's disease, associated with cognitive decline, fluctuations in alertness and cognition, visual hallucinations, and parkinsonism. Other clinical symptoms that can occur with DLB include dysautonomia and sleep disorders such as rapid-eye-movement sleep behavior disorder (RBD). The pathological criteria of DLB are associated with the location of Lewy body pathology and the extent of Alzheimer's pathology seen. Treatment is symptomatic. The genetic basis of DLB is being explored, and future studies will investigate ways to identify those most at risk for DLB prior to the onset of cognitive symptoms. PMID- 24234352 TI - Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia and is responsible for significant individual morbidity and mortality, and economic impact on the health care system. Neurodegeneration (including neuronal atrophy and/or loss) are attributed to extraneuronal toxic amyloid oligomers and proteins, intraneuronal neurofibrillary tangles consisting of hyperphosphorylated tau, region-specific diminished cerebral glucose metabolism, synaptic dysfunction, and mitochondrial dysfunction. Several of these pathologic changes may occur decades before symptom onset, leaving ample time for implementing prevention strategies that target the earliest stages of the disease. In recent years, a myriad of modifiable and nonmodifiable risk factors have been elucidated. We describe the latest criteria for the diagnosis of AD, including earliest diagnostic stage of preclinical AD, which has the highest potential for research, including diagnosis and disease modification. We discuss both FDA approved pharmacologic treatments, as well as nonpharmacologic strategies for AD therapeutics, including prevention via evidence-based, low-risk interventions. Genotype is an important consideration in managing patients on the AD continuum, as presence of the APOE epsilon4 allele may influence response to treatment. We present the most current evidence relating to pharmacogenomics, nutrigenomics, and distinctive nutritional requirements targeted toward AD. PMID- 24234354 TI - Frontotemporal dementia. AB - Frontotemporal dementia (FTD) encompasses several clinical syndromes that involve a progressive change in behavior and/or language; it is more common than Alzheimer's disease in early-onset dementia under the age of 60 years. In the behavioral variant of FTD (bvFTD) patients have social and emotional changes with prominent disinhibition, apathy, lack of empathy, changes in diet, and repetitive behaviors. Motor neuron disease or parkinsonism are seen in association with bvFTD. Frontal and/or temporal atrophy are often seen on structural brain imaging. Several pathological entities can cause bvFTD, and they are defined by the presence of specific abnormal protein accumulations. Most cases are characterized by accumulation of the proteins tau, TAR-DNA-binding protein-43 (TDP-43), and fused in sarcoma (FUS). Though most cases are sporadic, a variety of genes have been identified that cause autosomal dominant forms of FTD. The most common mutations occur in C9ORF72, MAPT, and GRN. No disease-modifying treatments have been currently identified, but limited evidence supports the use of antidepressants or neuroleptics in symptomatic management, and education regarding nonpharmacologic methods may be helpful to caregivers. PMID- 24234355 TI - Primary progressive aphasia and apraxia of speech. AB - Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: nonfluent/agrammatic, semantic, and logopenic variants. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. The clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech are reviewed in this article. The distinctions among these disorders for accurate diagnosis are increasingly important from a prognostic and therapeutic standpoint. PMID- 24234356 TI - Prion diseases. AB - Prion diseases are a group of diseases caused by abnormally conformed infectious proteins, called prions. They can be sporadic (Jakob-Creutzfeldt disease [JCD]), genetic (genetic JCD, Gerstmann-Straussler-Scheinker, and familial fatal insomnia), or acquired (kuru, variant JCD, and iatrogenic JCD). The clinical features associated with each form of prion disease, the neuroimaging findings, cerebrospinal fluid markers, and neuropathological findings are reviewed. Sporadic JCD is the most common form of human prion disease, and will be discussed in detail. Genetic prion diseases are caused by mutations in the prion related protein gene (PRNP), and they are classified based on the mutation, clinical phenotype, and neuropathological features. Acquired prion diseases fortunately are becoming rarer, as awareness of transmission risk has led to implementation of measures to prevent such occurrences, but continued surveillance is necessary to prevent future cases. Treatment and management issues are also discussed. PMID- 24234357 TI - Paraneoplastic and autoimmune encephalopathies. AB - Immune-mediated encephalitis is an increasingly recognized cause of neurologic dysfunction including behavioral change, psychosis, movement disorders, seizures, autonomic instability, and coma. Associated antineuronal antibodies are of two main subtypes, those targeting neuronal cell surface antigens, which are pathogenic, and nonpathogenic antibodies targeting intracellular antigens. Antibody identification aids in screening for underlying cancers and prediction of outcome. Cancer is found most commonly with antibodies targeting intracellular neural components. Certain cancers, such as small-cell lung carcinoma, and breast and ovarian cancer are particularly immunogenic. When cancer is detected, oncologic treatment should be followed with immunotherapy. Nonpathogenic antibody disorders respond poorly to treatment, whereas pathogenic antibodies predict a favorable response to immune treatment. If no cancer is identified, then ongoing surveillance is recommended for 5 years after detection of most antineuronal antibodies. PMID- 24234358 TI - Young-onset dementia. AB - Young-onset dementia is a neurologic syndrome that affects behavior and cognition of patients younger than 65 years of age. Although frequently misdiagnosed, a systematic approach, reliant upon attainment of a detailed medical history, a collateral history, neuropsychological testing, laboratory studies, and neuroimaging, may facilitate earlier and more accurate diagnosis with subsequent intervention. The differential diagnosis of young-onset dementia is extensive and includes early-onset forms of adult neurodegenerative conditions including Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementias, Huntington's disease, and prion disease. Late-onset forms of childhood neurodegenerative conditions may also present as young-onset dementia and include mitochondrial disorders, lysosomal storage disorders, and leukodystrophies. Potentially reversible etiologies including inflammatory disorders, infectious diseases, toxic/metabolic abnormalities, transient epileptic amnesia, obstructive sleep apnea, and normal pressure hydrocephalus also represent important differential diagnostic considerations in young-onset dementia. This review will present etiologies, diagnostic strategies, and options for management of young onset dementia with comprehensive summary tables for clinical reference. PMID- 24234360 TI - The genetics of dementia. AB - Over the past decade, there has been a dramatic evolution of genetic methodologies that can be used to identify genes contributing to disease. Initially, the focus was primarily on classical linkage analysis; more recently, genomewide association studies, and high-throughput whole genome and whole exome sequencing have provided efficient approaches to detect common and rare variation contributing to disease risk. Application of these methodologies to dementias has led to the nomination of dozens of causative and susceptibility genes, solidifying the recognition that genetic factors are important contributors to the disease processes. In this review, the authors focus on current knowledge of the genetics of Alzheimer's disease and frontotemporal lobar degeneration. A working understanding of the genes relevant to common dementias will become increasingly critical, as options for genetic testing and eventually gene specific therapeutics are developed. PMID- 24234361 TI - Application of immobilized hydrogenase to h2 storage in concentrated solutions of methyl viologen. AB - It has been found that immobilized cells ofC. pasteurianum possessing hydrogenase activity efficiently catalyze reversible reduction of concentrated (up to 0.5M) solutions of methyl viologen with H2. A 0.5M aqueous solution of methyl viologen dissolves 240 times as much H2 as pure water under the same pressure of hydrogen. The experimentally obtained levels of methyl viologen reduction and H2 evolution are in satisfactory agreement with theoretical calculations. The potential of concentrated solutions of methyl viologen containing immobilized hydrogenase as a H2 storage medium is discussed. PMID- 24234362 TI - Glucoamylase covalently coupled to porous glass. AB - Glucoamylase (EC 3.2.1.3) was immobilized to alkylamine porous glass with glutaraldehyde. The choice and pretreatment of carrier and conditions for immobilization have been investigated. The immobilized enzyme contained about 4.0 8.0% protein and its activity was about 1000-1700 U/g. Some characteristics of the immobilized enzyme and the native enzyme have been comparatively investigated. The optimum temperature and the pH stability of the preparation were almost identical to the native one. However, the optimum pH of bound glucoamylase shifted 1.3 pH units toward the alkaline side compared to the native one. The Michaelis constant(K m ) of bound glucoamylase for soluble starch was about four times higher than that of the native enzyme, whileK m values for maltose approached those of the native material. At 45?C the half-life of IMG was 104 days under operational conditions. Alkaline protease, alpha-amylase, asparaginase, and penicillin acylase were also chemically coupled to porous glass by the same method and high relative activities were obtained. PMID- 24234364 TI - Use of enzymes in peptide synthesis. AB - Recent experiments in several laboratories have emphasized the benefits of proteolytic enzymes as effective catalysts for the formation of peptide bonds for synthesis and semisynthesis. This review summarizes successful applications in both stepwise synthesis for small peptides and fragment condensation to produce large polypeptides and proteins. PMID- 24234363 TI - A compilation of amino acid analyses of proteins : XVII. Residues per thousand residues-4. AB - The amino acid analyses of 183 proteins, as residues per 1000 residues, are given. In addition the carbohydrate content and the content of any noncommon amino acids are also given. The sources of all proteins are presented. PMID- 24234365 TI - Homogeneous immunoassays. PMID- 24234366 TI - Resistance and adherence to the norms of genetic counseling. AB - Genetic counseling for women of advanced maternal age who are considering prenatal testing continues to be based on a principle of nondirectiveness. We interviewed 11 genetic counseling students and four counselors about how they experience and manage, in practice, the tensions between the ideology of nondirectiveness and the acknowledged reality that one can never be truly nondirective. We found that our respondents creatively resolve this tension simultaneously resisting and adhering to the values of nondirectiveness and information-giving-in individual and situation-specific ways. This resolution is facilitated by the extent to which information given to counselees is fluid, mobile and context-dependent, but these very features of "information" also have critical implications for both the norms and the practice of genetic counseling. PMID- 24234367 TI - A support group for couples who have terminated a pregnancy after prenatal diagnosis: Recurrent themes and observations. AB - Genetic Counselors are increasingly becoming involved in organizing and facilitating support groups for couples who have terminated a pregnancy because of an abnormal fetal diagnosis. This paper discusses recurrent themes which have emerged in the FATE (Feelings After the Termination Experience) support group which was founded in New Jersey in 1990. By becoming familiar with the issues we have observed in our support group, genetic counselors should be better able to understand and empathize with their patients who make the decision to terminate a much wanted pregnancy. They may also feel better prepared to become involved in organizing and facilitating such support groups. PMID- 24234368 TI - Parental guilt: The part played by the clinical geneticist. AB - Parents of children born with a disability often suffer feelings of inappropriate guilt and shame. Although some genetic counselors see their main task to be that of diagnosis and education, they also aim to relieve these feelings of guilt and shame. Little is known about the process of genetic counseling, and whether or not counselors achieve this aim. An exploratory study of one clinic, and one geneticist working with 30 families, using video recordings and taped interviews, indicated that this particular doctor sometimes succeeded in reducing guilt, either intentionally or unintentionally, but on one occasion guilt was iatrogenic, and increased rather than decreased. Further research is needed to examine other types and other styles of genetic counseling so that in future iatrogenic guilt can be avoided, and the distressing aspects of inappropriate guilt and shame reduced as much as possible. PMID- 24234359 TI - Neuroimaging biomarkers of neurodegenerative diseases and dementia. AB - Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer's disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson's disease with and without dementia, dementia with Lewy bodies, Huntington's disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID- 24234369 TI - Newborn screening for cystic fibrosis: Educational implications. AB - We examined the educational implications of newborn screening for cystic fibrosis (CF) as performed by combining the measurement of immunoreactive trypsin with analysis for the most common CF mutation, DeltaF508. Four out of 77 (5%) of maternity staff from 11 hospitals in rural New South Wales, Australia had learned about the salient features of the screening protocol from a pamphlet distributed from a central laboratory. In comparison, a didactic lesson resulted in a significantly greater (p<0.00006) number of maternity staff learning about the salient features of the screening protocol. Most maternity staff expanded their explanation to parents of newborn babies because of the didactic lesson. PMID- 24234370 TI - Resilience in siblings of children with sickle cell disease. AB - This pilot study was conducted to identify factors responsible for promoting resilience in siblings of children with sickle cell disease. Twenty siblings (10 17 years of age) of children (5-13 years) with sickle cell disease were selected from the Pediatric Clinic of Howard University Center for Sickle Cell Disease. The siblings responded to questionnaires, and the data obtained was analyzed by chi-square for association. The results indicated that age, birth order, and gender had no effect on resilience in the siblings. However, family size, number of parents in the home, sibling's knowledge of the illness, degree of morbidity of the illness, socioeconomic status of the family, and parents' attitudes and childrearing practices were all found to affect resilience. These findings provide additional insight into the psychosocial aspects of, and genetic counseling for sickle cell disease, as well as for other chronic genetic disorders. PMID- 24234372 TI - Forum: How much technology is too much? PMID- 24234371 TI - Counseling families with hereditary breast and ovarian cancer: A psychosocial perspective. PMID- 24234373 TI - One year of ESPR. PMID- 24234374 TI - Determination of atrazine in rainfall and surface water by enzyme immunoassay. AB - Rainwater and surface water from four sites in Germany (Bavaria and Lower Saxony) were analyzed for atrazine by enzyme immunoassay from June 1990 until October 1992. The limit of quantification of the immunoassay was 0.02 MUg/L with a middle of the test at 0.2 MUg/L. About 60 % of the samples contained measurable amounts of atrazine. Seasonal trends were observed, with the highest concentration in the summer months of up to 4 MUg/L for rainwater and up to 15 MUg/L for surface waters. The highest concentrations were found in agricultural areas, while in the investigated national parks up to 0.56 MUg/L could be detected in rain water. This points to long-range atmospheric transport from agricultural areas to pristine national parks. Samples from forest stands usually showed higher atrazine concentrations than samples from open fields. Deposition rates of 10 - 50 MUg/m(2) . yr were observed in the national parks and 10-180 MUg/m(2) . yr at the agricultural sites. Comparison of results obtained by enzyme immunoassay and GC/MS showed a good correlation of r = 0.95. PMID- 24234375 TI - On-line speciation of arsenical compounds in fish and mussel extracts by HPLC-ICP MS. AB - The separation and determination of sub-MUmol/l levels of six environmentally significant As compounds was accomplished by means of high performance liquid chromatography (HPLC) combined online with inductively coupled plasma mass spectrometry (ICP-MS). The species of interest (arsenite and arsenate, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine and arsenocholine) were quantified in fish and mussel extracts after separation on a Dionex AS7 column equipped with an on-guard AG7 column using a bicarbonate buffer as the mobile phase in a gradient mode. The species thus eluted were directly forwarded to the ICP-MS detector. The detection power of the overall system allows each As form to be determined at concentrations as low a 0.0013-0.0027 MUmol 1(-1). PMID- 24234376 TI - Deposition of semivolatile organic compounds to spruce needles : II. Experimental evaluation of the relative importance of different pathways. AB - The accumulation of atmospheric HCB, Lindane, DDT, DDE and the PCB congeners 52, 101, 138, 153 and 180 in spruce needles (Picea abies) was investigated at outdoor locations and in greenhouses supplied with ambient air. The air supply of the greenhouses was modified to dinstinguish between gaseous and particle-associated deposition of the compounds. Accumulation of the compounds occurred in all spruce except those grown in the greenhouse where the gaseous concentration of the compounds was reduced. Spruce grown in the greenhouse supplied with particle-free ambient air behaved similarity to those grown outdoors. Protecting the spruce located outdoors from rain did not affect the accumulation. The results show that under spring and summer conditions at a typical central European rural environment dry gaseous deposition is the dominant pathway of these compounds to needles. PMID- 24234377 TI - Deposition of semivolatile organic compounds to spruce needles : I. Calculation of dry and wet fluxes. AB - The deposition of atmospheric tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene,alpha-HCH,gg-HCH, DDT, DDE and the PCB congeners 52, 101, 138, 153 and 180 to spruce needles (Picea abies) was estimated for a period of 9 months. Accumulation in spruce as a result of dry gaseous deposition, particle bound deposition and wet deposition was calculated on the basis of the corresponding deposition rates and the compounds' concentrations in the different atmospheric compartments. The comparison of the calculated values with the concentrations of the compounds measured in 9-month-old spruce needles showed that for many compounds each deposition pathway could explain a large pan of the concentrations found in the needles. PMID- 24234378 TI - Toxicity testing of highly volatile chemicals with green algae : A new assay. AB - A gas-tight system for toxicity testing of highly volatile chemicals with the green algaChlamydomonas reinhardtii was developed. The procedure permits maintenance of constant and defined concentrations of the tested compounds in the vessels. To ensure sufficient CO2-supply, new bipartite test vessels were used. These vessels allowed spatial separation of a HCO3-/CO 3 (2-) buffer used for CO2 supply and the alga culture to avoid growth inhibition due to ionic strength. Several volatile chlorinated hydrocarbons have been tested. Their EC10 values were several orders of magnitude lower than those obtained with open test systems. PMID- 24234379 TI - Uptake and metabolism of 2,4,6-trinitrotoluene in higher plants. AB - The fate of the explosive 2,4,6-TNT in plants is of major interest. Therefore, a method was developed to analyse TNT and derivatives in plant tissue. The method was utilized to investigate the uptake and metabolism of TNT inMedicago sativa andAllium schoenoprasum grown in hydroponic cultures containing TNT levels of 0.1 to 10 mg/1. Detectable concentrations of nitrotoluenes were significantly higher inAllium schoenoprasum than inMedicago sativa. The uptake of TNT in plants was directly related to the initial TNT level. The principal nitroaromatic components in roots and shoots of both plant species were identified as 4-ADNT and 2-ADNT in equal amounts, with substantially less TNT. PMID- 24234380 TI - A wind tunnel for measuring the gaseous losses of environmental chemicals from the soil/plant system under field-like conditions. AB - Volatilization from treated areas is a major source of pesticide residues in air, fog, and rain. This may lead to long-range transport of pesticide residues to remote areas. Up to now most information on pesticide volatilization has come from laboratory experiments under controlled conditions. A new system has been designed and developed to measure the volatile losses of(14)C-labelled chemicals after application; the method compares with agricultural practice of treating soils or plants grown in lysimeters. Sensitive analytical methods guarantee a distinction between residues of unchanged pesticide, its metabolites or(14)CO2 as a mineralization product released into the air. PMID- 24234381 TI - Preface. PMID- 24234382 TI - Fate of pulp mill effluent compounds in a finnish watercourse. AB - Chloroorganic chemicals emitted from the pulp and paper mill at nekoski in central Finland were monitored for several years. Concentration time series are used for evaluating the environmental fate and the applicability and validity of an exposure models. Fitted elimination rates of 3,4,5-Tri-, 4,5,6-Tri-, Tetrachloroguaiacol and 2,4,6-Trichlorophenol are approx. 0.22 d(-1), or rather the half-lives are approx. 3 days. The elimination is most likely by biodegradation and transport-controlled. For 2,3,6-trichloro-p-cymene, fate simulations indicate significant volatilization and sedimentation. Good agreement is achieved with a one-dimensional steady-state box model, except for concentrations in fish. For a reliable assessment of environmental damage, laboratory experiments, monitoring and simulations need to be in tune. PMID- 24234383 TI - Guide values for contaminated sites in Baden-Wurttemberg. AB - The treatment of hazardous sites in Baden-Wurttemberg is based on three legal documents: the state waste disposal art (LAbfG, 1990), the assessment committee directive (KommissionsVO, 1990), and the guide values directive (UM & SM B-W, 1993). The guide values directive was commonly issued by the Ministry of Labor, Health and Social Affairs and the Ministry of the Environment of the state of Baden-Wurttemberg (UM & SM B-W, 1993) and contains a three-level hierarchy of numerical criteria and rules which serve as both screening levels during the investigation and as remediation objectives. The decision for the appropriate level of remediation is based on feasibility and environmental balance considerations. The levels are ordered as follows: * Level 1 (Background-Values) On principle, all remediations have to be based first on background levels. In the case of lack of feasibility or negative environmental balance for level-1 objectives use-specific requirements are considered next. * Level 2 (Assessment Values for Worst Case Exposure Conditions) The generic requirements underlying level 2 afford appropriate protection for humans regarding the most sensitive uses of the environment. At least four resources are considered on this level: Ground-water as such and its use, the health of humans on contaminated sites, and soil with respect to growth and quality of plants. Barriers against migration of the contaminants, the effect of dilution, and abandonment of certain uses, etc., are not taken into consideration on level 2. * Level 3 (Site-Specific Requirements) Lack of feasibility or a negative environmental balance of level-2 objectives lead to consideration of site-specific circumstances which may alleviate the requirements. With respect to groundwater, the distinction is again necessary between groundwater as a resource and the use of groundwater. On level 3 the guideline gives rules of how to derive site-specific remediation objectives for groundwater in the form of concentrations and fluxes of contaminants after taking into account barriers, dilution, and the abandonment of uses. The guideline is the only directive of its kind in the world that regulates both concentrations and fluxes of contaminants into groundwater. PMID- 24234384 TI - Polychlorinated dibenzo-p-dioxins (PCDDs) and furans (PCDFs) in urban air and deposition in the United Kingdom. AB - Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) have been monitored in air and deposition at four UK urban sites (London, Cardiff, Manchester and Stevenage) since the beginning of 1991; data from the first 2 years are presented here. Median Sigma2,3,7,8-substituted PCDD/F concentrations in air were 3.2, 4.0, 3.5 and 2.6 pg/m(3) respectively for London, Cardiff, Manchester and Stevenage. Median Sigma2,3,7,8-substituted PCDD/F deposition fluxes were 1.5 ng/m(2)/day in London, 1.4 ng/m(2)/day in Cardiff and Manchester and 0.79 ng/m(2)/day in Stevenage. Seasonal variations in the PCDD/F concentrations were observed at all sites for both air and deposition, with concentrations/fluxes generally elevated during the winter. PMID- 24234385 TI - Survey on the series. PMID- 24234386 TI - Part IV: Life Cycle Assessment (LCA). PMID- 24234387 TI - Institutions active in environmental science, research and technology in Italy. PMID- 24234389 TI - Industrial back belts and low back pain: Mechanisms and outcomes. AB - The recent increased utilization of industrial back belts as personal protective equipment in the workplace has generated considerable controversy among occupational health and safety professionals in the United States. The purpose of this article is to review the literature regarding proposed mechanisms of action of these devices and studies related to outcome of belt utilization in the prevention of low back pain and disability in the workplace. At the present time, neither the suspected mechanisms of action nor the efficacy of these devices in the primary, secondary, and tertiary prevention of work-related low back pain has been adequately demonstrated in clinical trials. As a result, generally accepted guidelines regarding the safe use of belts in the occupational setting have not been established. Based on this review it is recommended that further well controlled, prospective, randomized clinical trials are necessary to evaluate the effectiveness of these devices as personal protective equipment. During the interim, the decision to prescribe belts to employees in the workplace should be at the discretion of an adequately trained occupational health care provider. These devices should not be provided as an alternative to appropriate administrative and/or engineering controls. PMID- 24234390 TI - Lifestyle correlates of Carpal Tunnel Syndrome. AB - The potential for predicting membership in a Carpal Tunnel Syndrome group (CTS) vs. a non-CTS group was evaluated for five psychological variables (i.e., life events stress, perceived stress, self-management habits, cognitive self-control skills, and lifestyle organization) and three physical variables (i.e., general physical symptoms, suspected medical risk for CTS, and generic musculoskeletal problems). The subjects included 50 pairs of workers, with each pair having one worker who had CTS and the other who had not. A logistic regression analysis indicated that five of the measures (three psychological and two physical) were significant single model predictors of membership in CTS and non-CTS groups. The most efficient multifactor model in predicting CTS appeared to be a combination of measures reflecting generic musculoskeletal problems and lifestyle organization. PMID- 24234391 TI - Work absence in a cohort with benign back pain: Prospective study with 10 year follow-up. AB - A cohort of nearly 1000 men with some level of back problems at time of their drafting were prospectively followed over a 10-year period. In connection with drafting for military service they answered a questionnaire and were clinically examined. The main aim of the study was to follow work absence and the impact of back pain on everyday life. Everyday problems because of the back pain did not significantly increase over the follow-up period and self-reported work absence decreased. Heavy work was associated with an increased risk for work absence but not for back/neck problems. PMID- 24234392 TI - Variability of isometric and isotonic leg exercise: Utility for detection of submaximal effort. AB - A number of studies have investigated the use of variability measures in the detection of submaximal or insincere efforts in strength testing. The underlying assumption of these approaches is that submaximal efforts will be more variable than maximal efforts. Previous studies have investigated the variability of torque production in isometric or isokinetic tasks with mixed results. The present study investigated the variability of torque production and velocity in isometric and isotonic leg extension tasks, respectively. Fifteen asymptomatic subjects participated in a within-subject counterbalanced design in which they were asked to perform maximally and submaximally in both isometric and isotonic leg extension tasks. Results indicated that both isometric and isotonic tasks showed greater variability (measured by coefficient of variation) in the submaximal effort condition. However, the sensitivity to detect submaximal efforts was much greater for the isotonic velocity variability condition. It was concluded that the isotonic approach showed promise for clinical application, but that the isometric task had unacceptably poor classification rates, consistent with previous research. PMID- 24234393 TI - Scanning paraspinal surface EMG: A method for corroborating post-treatment spinal and related neuromusculoskeletal symptom improvement. AB - This study evaluated the relationship between post-treatment paraspinal surface EMG improvement in the static sitting and standing postures, with patient post treatment subjective regional spinal pain and/or related neuromusculoskeletal symptoms, using hand held scanning electrodes. A retrospective review of consecutive files of patients who had presented with regional spinal pain and/or related neuromusculoskeletal symptoms was undertaken. The files considered for this study needed to meet a set of pre-established criteria in order to qualify for selection. Forty-two patients met the criteria for review. Forty-one patients reported post-treatment reduction in their symptoms. Of the 42 patients indicating improvement on post-treatment static scanning SEMG examination, 41 (97.6%) had indicated symptomatic improvement as well. The findings warrant further investigation to determine whether hand-held surface EMG scanners can be reliably utilized as a post-treatment objective instrument for determining symptomatic improvement in commonly seen physical conditions of the spine which are of spinal biomechanical/postural etiology. PMID- 24234395 TI - Capsule Commentary on Bump et al., Hold-Over Admissions: Are They Educational for Residents? PMID- 24234394 TI - Cost-effectiveness of procalcitonin-guided antibiotic therapy for outpatient management of acute respiratory tract infections in adults. AB - BACKGROUND: Two clinical trials suggest that procalcitonin-guided antibiotic therapy can safely reduce antibiotic prescribing in outpatient management of acute respiratory tract infections (ARTIs) in adults. Yet, it remains unclear whether procalcitonin testing is cost-effective in this setting. OBJECTIVE: To evaluate the cost-effectiveness of procalcitonin-guided antibiotic therapy in outpatient management of ARTIs in adults. DESIGN: Cost-effectiveness model based on results from two published European clinical trials, with all parameters varied widely in sensitivity analyses. PATIENTS: Two hypothetical cohorts were modeled in separate trial-based analyses: adults with ARTIs judged by their physicians to require antibiotics and all adults with ARTIs. INTERVENTIONS: Procalcitonin-guided antibiotic therapy protocols versus usual care. MAIN MEASURES: Costs and cost per antibiotic prescription safely avoided. KEY RESULTS: We estimated the health care system willingness-to-pay threshold as $43 (range $0 $333) per antibiotic safely avoided, reflecting the estimated cost of antibiotic resistance per outpatient antibiotic prescribed. In the cohort including all adult ARTIs judged to require antibiotics by their physicians, procalcitonin cost $31 per antibiotic prescription safely avoided and the likelihood of procalcitonin use being favored compared to usual care was 58.4 % in a probabilistic sensitivity analysis. In the analysis that included all adult ARTIs, procalcitonin cost $149 per antibiotic prescription safely avoided and the likelihood of procalcitonin use being favored was 2.8 %. CONCLUSIONS: Procalcitonin-guided antibiotic therapy for outpatient management of ARTIs in adults would be cost-effective when the costs of antibiotic resistance are considered and procalcitonin testing is limited to adults with ARTIs judged by their physicians to require antibiotics. PMID- 24234396 TI - Marijuana use and health in primary care. PMID- 24234397 TI - Arrhythmia risk associated with sleep disordered breathing in chronic heart failure. AB - The intersecting relationships of sleep disordered breathing (SDB), arrhythmogenic risk and chronic heart failure (HF) are complex and most likely multi-directional and synergistic. Autonomic dysfunction is a common pathophysiological feature of each of these entities. Intermittent hypoxia, hypercapnia, mechanical cardiac influences due to upper airway obstruction and rostral fluid shifts are SDB-specific mechanisms which may trigger, perpetuate and exacerbate HF and arrhythmogenesis. Specific pathophysiological mechanisms will vary according to the predominance of central as compared to obstructive sleep apnea. The risk of cardiac arrhythmias and HF attributable to SDB may be considerable given the high prevalence of SDB and its likely physiologic burden. The current review focuses on the data, which have accrued elucidating the specific contributory mechanisms of SDB in cardiac arrhythmias and HF, highlighting the clinical relevance and effects of standard SDB treatment on these outcomes, and describing the role of novel therapeutics. PMID- 24234398 TI - Novel blockers of the renin-angiotensin-aldosterone system in chronic heart failure. AB - Because of the impressive record of ACE inhibitors in patients with heart failure with reduced ejection fraction, the renin-angiotensin-aldosterone system continues to be pursued as a therapeutic target. Furthermore, the optimal treatment of patients with heart failure with preserved ejection fraction remains unclear. Early trials of direct renin inhibitors suggested that they may have a role, but recent results have not been encouraging. Preliminary trials of angiotensin-receptor/neprilysin inhibitors look positive. Whether these or other drugs will alter current recommendations remains to be seen. PMID- 24234400 TI - Effective strategy for managing H7N9 virus infection. PMID- 24234399 TI - Neuregulin as a heart failure therapy and mediator of reverse remodeling. AB - The beta isoform of Neuregulin-1 (NRG-1beta), along with its receptors (ErbB2-4), is required for cardiac development. NRG-1beta, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1beta on cardiac function. In addition to the possible role for recombinant NRG-1betas as heart failure therapies, endogenous NRG-1beta/ErbB signaling appears to play a role in restoring cardiac function after injury. The potential mechanisms by which NRG-1beta may act as both a therapy and a mediator of reverse remodeling remain incompletely understood. In addition to direct effects on cardiac myocytes NRG-1beta acts on the vasculature, interstitium, cardiac fibroblasts, and hematopoietic and immune cells, which, collectively, may contribute to NRG-1beta's role in maintaining cardiac structure and function, as well as mediating reverse remodeling. PMID- 24234402 TI - The accumulation of metals and toxic effects in Nereis virens exposed to pulverised fuel ash. AB - The marine polychaete worm Nereis virens was used to study the bioaccumulation patterns of metal exposures with pulverised fuel ash (PFA). Juvenile N. virens were exposed for 12 weeks to sediments comprised of 100% PFA, 50% PFA-50% clean sand, a reference sediment (contaminated harbour-dredged material) and a clean sand control. Mortality after the first 4 weeks was high at 32-45% in the four sediments. However, this declined to a few percent during the following 8 weeks. Growth expressed as biomass (wet weight) was reduced in bout PFA treatments and the reference sediment. Heavy metal accumulation in the tissues of N. virens was characterised as follows: a group of elements showed negligible to low accumulation (Cd, Cr, Ni, and Zn), As and Cu wich showed a definite, but moderate accumulation: and finally Se, which showed a low accumulation rate, where an uptake equilibrium was not reached after 9 weeks. It is concluded that acute toxic effects did not occur but a population of N. virens inhabiting a PFA dumping site could be affected by high Se concentrations. PMID- 24234403 TI - A model for the maximum credible hourly impact on any ground receptor from point sources with momentumdominated plume rise. AB - A pollutant dispersion model is developed, allowing rapid evaluation of the maximum credible one-hour-average concentration on any given ground-level receptor, along with the corresponding critical meteorological conditions (wind speed and stability class) for stacks with momentum-dominated plume rise in urban or rural areas under buoyancy or no buoyancy induced dispersion. Site-specific meteorological data are not required, as the computed concentrations are maximized against all credible combinations of wind speed, stability class, and mixing height.The analysis is based on the dispersion relations of Pasquill Gifford and Briggs for rural and urban settings respectively, the buoyancy induced dispersion correlation of Pasquill, the wind profile exponent values suggested by Irwin, the momentum plume rise relations of Briggs, as well as the Benkley and Schulman's model for the minimum mixing heights.The model is particularly suited for air pollution management studies, as it allows fast screening of the maximum impact on any selected receptor and evaluation of the ways to have this impact reduced. Also, for regulatory purposes, as it allows accurate setting of minimum stack height requirements as function of the exit gas volume and velocity, the pollutant emission rates and their hourly concentration standards, as well as the source location relative to sensitive receptors. PMID- 24234401 TI - Genetically modified pigs to model human diseases. AB - Genetically modified mice are powerful tools to investigate the molecular basis of many human diseases. Mice are, however, of limited value for preclinical studies, because they differ significantly from humans in size, general physiology, anatomy and lifespan. Considerable efforts are, thus, being made to develop alternative animal models for a range of human diseases. These promise powerful new resources that will aid the development of new diagnostics, medicines and medical procedures. Here, we provide a comprehensive review of genetically modified porcine models described in the scientific literature: various cancers, cystic fibrosis, Duchenne muscular dystrophy, autosomal polycystic kidney disease, Huntington's disease, spinal muscular atrophy, haemophilia A, X-linked severe combined immunodeficiency, retinitis pigmentosa, Stargardt disease, Alzheimer's disease, various forms of diabetes mellitus and cardiovascular diseases. PMID- 24234404 TI - Effect of trivalent and hexavalent chromium on renal and hepatic tissue glycogen metabolism of a fresh water teleost Anabas scandens. AB - The in vivo toxic impact of chromium in its two forms (trivalent and hexavalent) on glycogen metabolism in the liver and kidney of a fresh water teleost Anabas scandens was studied. In a sub-chronic exposure of 30 days, depletion of glycogen and glucose reserves reflected in the activity patterns of glycogen phosphorylases 'a and ab'. While both forms of chromium induced alterations in enzyme activities and metabolite levels in the two tissues, Cr(+6) exerted greater effects in the kidney. PMID- 24234405 TI - Ozone biomonitoring in Northern Italy. AB - This report presents the results of an ozone monitoring experience performed with tobacco indicator plants (Nicotiana tabacum L. cv. 'Bel-W3'). These bioindicators were exposed to ambient air in 23 sites in Northern Italy from 27 April 1987 to 21 October 1987. Typical ozone-induced leaf necrosis was observed in every site. The percentage increase in injured leaf area was estimated weekly and a Leaf Injury Index (LII) was calculated. The weekly series of LIIs were statistically inspected for spatial and temporal relationships. Sample correlation coefficients were statistically significant for almost every possible pair of sites. The time series properties of ten series of LIIs with no missing data were analyzed using Box-Jenkins models. An autoregressive first order model, or AR(1), was selected to remove the autocorrelation from these series. Linear correlation coefficients between 'prewhitened' (i.e. from which autocorrelation had been removed) pairs of LII series were statistically significant. Hence synchronous variations in leaf necrosis could only be related to the regional diffusion of tropospheric ozone. PMID- 24234406 TI - Editors' note. PMID- 24234407 TI - Ontogenic development of chemical defense by seedling resin birch: Energy cost of defense production. AB - Whether production of chemical defenses by plants is or is not an energetically costly process is an important, but unresolved, question in chemical ecology. We suggest studies of the ontogenetic development of plant defense systems can help resolve the question. As an example of this approach to the cost question, we explore the problems associated with production of immobile chemical defenses that defend juvenile resin birches against browsing by mammals. From this exploration we draw two conclusions: (1) Shortly after germination, production of chemical defenses by small-seeded species, such as birch, is energetically costly. (2) Opposing selection for defense versus competitive ability in the seedling stage of birch has resulted in a trade-off in allocation of carbon to production of immobile chemical defense versus allocation of carbon to production of storage reserves. We suggest this trade-off results in a large indirect cost of defense because carbon used for production of immobile chemical defenses is unavailable for support of growth in the future, but stored carbon can be used to support future growth. PMID- 24234408 TI - Plasticity in allocation of nicotine to reproductive parts inNicotiana attenuata. AB - Although little is known about the patterns of chemical defense allocation in reproductive tissues, optimal defense theory predicts a high constitutive allocation due to the tissues' high fitness value. To examine this prediction, we quantified the short- and long-term changes in the nicotine pools of reproductive tissues in response to both floral and leaf damage. Recently opened flowers (stage 5 capsules) do not alter their nicotine pools within a day in response to herbivory byManduca sexta larvae or mechanical damage to the corolla. Similarly, leaf damage during both vegetative and reproductive growth does not influence the nicotine pools of the first three stage-5 capsules produced. However, the nicotine pools of capsules produced later in reproductive growth were significantly larger (1.2- to 1.9-fold) on plants with leaf damage. These differences in floral nicotine pools were a result of both increases in nicotine pools of capsules on damaged plants and decreases in the nicotine pools of capsules on undamaged plants during reproductive growth. Leaf damage did not affect the rate of capsule maturation or the mass of stage-5 capsules at any time during reproductive growth. An allometric analysis of nicotine pools and biomass of reproductive parts in all stages of development from damaged and undamaged plants demonstrates that damaged plants allocated a significantly larger quantity of nicotine to reproductive parts in all stages of development than did undamaged plants. Given that nicotine is thought to be synthesized in the roots and transported to leaves and reproductive parts, nicotine could be allocated to reproductive parts in proportion to the number of developing capsules on a plant. We excised the first 27 stage-5 capsules on plants with and without leaf damage, with the expectation that plants with fewer capsules would allocate a larger amount of nicotine to the remaining capsules. In contrast to the prediction of this passive allocation model, floral excision did not affect nicotine pools on plants with or without leaf damage. These results demonstrate that the allocation of nicotine to reproductive parts is more strongly influenced by damage to vegetative rather than reproductive tissues. Reproductive parts are constitutively defended over the short term, but the set points for defense allocation are apparently increased by damage to vegetative tissues during reproductive growth. The decrease in allocation of nicotine to reproductive parts in undamaged plants during reproductive growth suggests an optimization of resource allocation as plants realize their potential fitness. PMID- 24234409 TI - Tracking variable environments: There is more than one kind of memory. AB - Three kinds of memory help herbivores track changes in the environment. The first is the collective memory of the species with genetic instructions that have been shaped by the environment through millennia. This includes skin and gut defense systems. Auditory and visual stimuli and sensations of pain impinge upon the skin defense system that evolved in response to predation. The taste of food and the sensations of nausea and satiety are an integral part of the gut defense system that evolved in response to toxins and nutrients in plants. The second kind of memory in social mammals is represented by the mother, a source of transgenerational knowledge, who increases efficiency and reduces risk of learning about foods and environments. The third kind of memory is acquired by individual experience. Postingestive feedback from nutrients and toxins enables individuals to experience the consequences of food ingestion and to adjust food preference and selection commensurate with a food's utility. The three memories interact, each linking the past to the present, and collectively shape the present and future of every individual. Thus, the dynamics of foraging involves appreciating the uniqueness of individuals and subgroups of animals, each with their own genetic and behavioral history, and recognizing that foraging behaviors may not be stable, optimal, or even predictable in the conventional sense. PMID- 24234410 TI - Turnabout is fair play: Secondary roles for primary compounds. AB - Chemically based resistance of plants to herbivorous insects is today essentially synonymous with allelochemically based resistance; the importance of plant secondary compounds in determining patterns of host-plant utilization has been established in a wide variety of insect-plant interactions. In contrast, primary metabolites, those involved in fundamental plant physiological processes, are rarely considered to be major determinants of host-plant resistance despite the fact that, as insect nutrients, they can have profound effects on behavior and physiology. The degree to which variation in plant primary metabolism results from the selective impact of herbivory may be greatly underestimated in that the biosynthetic and structural diversity of primary metabolites and the consequences of that diversity on herbivores are rarely taken into account in most studies of insect preference and performance. Qualitative and quantitative variation in the production of primary metabolites can result from herbivore selection pressure if production of primary metabolites is under genetic control and if plant fitness in the presence of herbivores is associated in a predictable way with genetically based primary metabolite variation. Variation in primary metabolism is likely to be particularly effective as a defense against highly oligophagous herbivores with limited mobility, especially those confined to structures containing allelochemicals that could neutralize the benefits associated with compensatory feeding. PMID- 24234411 TI - Bioactivity of beaver castoreum constituents using principal components analysis. AB - North American beaver (Castor canadensis) were observed to sniff from the water and make land visits to some synthetic chemical components of castoreum placed on experimental scent mounds (ESM). In previous analysis, the elicitation (presence/absence), completeness, and/or strength (number, duration) of these key responses served as separate measures of biological activity. In this paper, we used principal components analysis (PCA) to combine linearly six related measures of observed response and one index of overnight visitation calculated over all trials. The first principal component accounted for a majority of the variation and allowed ranking of the samples based on their composite bioactivity. A second PCA, based only on response trials (excluding trials with no responses), showed that responses to the synthetic samples, once elicited, did not vary greatly in completeness or strength. None of the samples evoked responses as complete or strong as the castoreum control. Castoreum also elicited more multiple land visits (repeated visits to the ESM by the same individual or by more than one family member) than the synthetic samples, indicating that an understanding of the castoreum chemosignal requires consideration of responses by the family unit, and not just the land visit by the initial responder. PMID- 24234412 TI - Pheromone-mediated mating in the aphid parasitoid,Aphidius nigripes (hymenoptera: Aphididae). AB - Mating in the aphid parasitoid,Aphidius nigripes, is mediated by a female sex pheromone that stimulates both upwind flight and courtship behavior by males. There is no evidence of any overt behavior associated with the release of the pheromone, but bioassay results, using female extracts, suggest that the pheromone is produced in the abdomen, although it may be actively released from the entire body surface. Age does not appear to have a major influence on either pheromone production by the female or on male responsiveness. However, field data suggest the presence of a strong diel periodicity in the emission of and/or receptivity to the pheromone. Laboratory bioassay results indicated diel changes in the male response but more refined techniques are needed to determine if such periodicity exists in pheromone production by females. Following mating, female pheromone production is significantly reduced. The potential use of the parasitoid sex pheromone in integrated management of aphids is discussed. PMID- 24234413 TI - Multifunctional communication inRiptortus clavatus (Heteroptera: Alydidae): Conspecific nymphs and egg parasitoidOoencyrtus nezarae use the same adult attractant pheromone as chemical cue. AB - The bean bug,Riptortus clavatus lays scattered eggs (as opposed to the egg masses of pentatomids) on host as well as nonhost plants. Therefore, the first feeding stage (second-instar) nymphs emerging from eggs laid on nonhost plants need a signal that enables them to locate a food source at the lowest energy cost. Male released (E)-2-hexenyl (E)-2-hexenoate, (E)-2-hexenyl (Z)-3-hexenoate, and myristyl isobutyrate play the double role of attractant pheromone for adults as well as aggregation pheromone, which enables the second-instar nymphs to find the host food plant. These male-specific semiochemicals are released only when foodstuff is available. On the other hand, females ofOoencyrtus nezarae, the most effective parasitoid of the host in Kumamoto, Japan (where the field experiments were conducted), utilize these semiochemicals as kairomones in order to locate the potential host community. Field experiments revealed that the synthetic pheromone rivaled 10 live males in the attraction of adults and second-instar nymphs. Captures of the egg parasitoidO. nezarae females in cylindrical sticky traps were significantly higher in traps baited with the synthetic semiochemicals than in control traps. The number of females captured was significantly higher than the number of males, although the captures in the sticky suction trap system revealed that the populations of male and female were not significantly different. PMID- 24234414 TI - Quantitative high-resolution gas chromatographic determination of stereoisomeric composition of chiral volatile compounds in the picogram range by ec-detection. AB - A gas chromatographic method using electron capture detection for determination of the stereochemical composition of chiralolatile compounds, e.g., pheromones, at the picogram level is described. Substances of interest are analyzed as pentafluorobenzoate derivatives on fused silica capillary columns coated with CP Sil-88. This method was developed primarily for the quantitative analyses of stereoisomerism of the pheromone precursor, diprionol, in female sawflies,Neodiprion sertifer. It was possible to separate the stereoisomers showing (2S, 3S, 7R) and (2S, 3S, 7S) configurations. Resolution of the (2S, 3S, 7S)- and (2S, 3R, 7R)-diastereomers was high enough to allow the quantification of these stereoisomers. A quantitative analysis of the diprionol production in individualN. sertifer females yielded 7.5-9.7 ng/female. PMID- 24234415 TI - Enantiomeric composition of ipsdienol: A chemotaxonomic character for north American populations ofIps spp. in thepini subgeneric group (coleoptera: Scolytidae). AB - Thirty-five populations ofIps pini (Say) and one population each ofIps avulsus (Eichhoff) andIps bonanseai (Hopkins) were analyzed for the enantiomeric composition of ipsdienol (2-methyl-6-methylene-2,7-octadien-4-ol). Populations ofI. pini occur as at least two distinct regional pheromone variants: New York type [32%-(-) to 56%-(-)-ipsdienol] and California type [94%-(-) to 98%-(-) ipsdienol]. A third phenotype may occur in southeastern British Columbia, Idaho, and Montana [91%-(-) to 95%-(-)], possibly indicating a zone of hybridization. Populations of the New York type occur in southwestern British Columbia, Alberta, Saskatchewan, Minnesota, and Wisconsin suggesting a continuum through the Canadian provinces and Lake States. The presence of the New York type in western Canada is likely linked to the Quaternary history of the transcontinentally distributed host,Pinus banksiana Lamb. MaleI. avulsus [~25%-(-)] and maleI. bonanseai [-29%-(-)] both produce ipsdienol, but not ipsenol. Production of ipsdienol by maleI. pini was evaluated in six differentPinus spp. hosts. Following transfer of maleI. pini to hosts other than the host of origin, the percentage of the (-)-enantiomer of ipsdienol declined when compared to production in the host of origin. PMID- 24234416 TI - Why not be a queen? Regioselectivity in mandibular secretions of honeybee castes. AB - Both female castes of the honeybee (Apis mellifera L.) synthesize hydroxylated 2(E)-decenoic acids in their mandibular glands. Queens produce 9-hydroxy-2(E) decenoic acid as part of their primer pheromone, while workers produce the regioisomeric 10-hydroxy acid, probably as a larval food source and an antiseptic secretion. Both workers and queens are biosynthetically competent to produce the other caste's dominant hydroxylated compound, as both isomers can be detected in queens and workers. We investigated the source of the caste-determined regioselectivity of hydroxy acid biosynthesis by investigating the production and interconversion of these compounds in isolated worker honeybee mandibular glands with specifically deuterated precursors. Gas chromatographic-mass spectroscopic identification of the labeled product indicates that octadecanoic acid is converted into 10-hydroxy-2(E)-decenoic acid with higher efficiency than either hexadecanoic or decanoic acids. 10-Hydroxydecanoic acid is readily converted into 10-hydroxy-2(E)-decenoic acid as expected in the beta-oxidation process. The saturated and unsaturated 10-hydroxy acids are oxidized to the corresponding ten carbon diacids. PMID- 24234417 TI - Testing the "new associations" biological control concept with a tachinid parasitoid (Euclytia flava). AB - Males of the spined soldier bug,Podisus maculiventris (Heteroptera: Pentatomidae), produce an attractant pheromone that is exploited as a host finding kairomone by a complex of parasitic species. The capability to catch hundreds of a generalist tachinid fly parasitoid,Euclytia flava, alive in traps baited with the pheromone ofP. maculiventris provided an opportunity to test the premise of the "new associations" biological control concept. The hypothesis that host species newly associated with a parasitoid are maladapted relative to native native associations was tested by givingE. flava females a choice between native and exotic stink bugs (Heteroptera: Pentatomidae). WildE. flava females preferred to oviposit on exotic pentatomid species rather than indigenous, known host species, both in field traps baited with the pheromone of a native host and in the laboratory. Data presented here demonstrate that an invader may be vulnerable to native parasitoids in one aspect of the parasitism process (acceptance), yet go unrecognized as a potential host. PMID- 24234418 TI - Semiochemicals from bark beetles: New results, remarks, and reflections. AB - A brief survey is given about recent results in the identification of semiochemicals in bark beetles: Males ofIps sexdentatus (Boern.), stressed by the attack on resinous trees produce large amounts of 3(S)-1-methyl-5-(1-hydroxyl-1 methylethyl)-cyclohexa-1,3-diene. The compound appears to be derived from Delta(3)-carene and acts as a repellent. Males ofIps typographus (L.), stressed through the attack on unsuitable host material release 3-methyl-7-methylene 1,3(E), 8-nonatriene, which seems to act as a repellent. The odor bouquet of three species ofPityogenes is described. The occurrence of (+)-grandisol and other compounds related to weevil pheromones points to a close relation between Scolytidae and Curculionidae. Females ofDendroctonus simplex (Le Conte) use (-) frontalin as the main pheromone. 6-Methyl-6-hepten-2-one, a minor component among the volatile compounds released by the females, is regarded as a possible precursor of frontalin. Similarly, (2R,5S)-2(1-hydroxyl-1-methylethyl)-5 methyltetrahydrofuran, pityol, a pheromone ofPityophthorus spp., is regarded to at least share a common biogenetic precursor with 6-methyl-5-hepten-2-ol, sulcatol. A new bicylic acetal, 2-ethyl-1,5-dimethyl-6,8 dioxabicyclo[3.2.1]octane, is described as an aggregation pheromone of the beech bark beetle,Taphrorychus bicolor (Herbst). Structural relationships between bark beetle pheromones and plant volatiles are discussed. PMID- 24234419 TI - Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione. AB - The intestinal Ca2+ absorption is inhibited by menadione (MEN) through oxidative stress and apoptosis. The aim of this study was to elucidate whether the antioxidant and antiapoptotic properties of melatonin (MEL) could protect the gut against the oxidant MEN. For this purpose, 4-week-old chicks were divided into four groups: (1) controls, (2) treated i.p. with MEN (2.5 MUmol/kg of b.w.), (3) treated i.p. with MEL (10 mg/kg of b.w.), and (4) treated with 10 mg MEL/kg of b.w after 2.5 MUmol MEN/kg of b.w. Oxidative stress was assessed by determination of glutathione (GSH) and protein carbonyl contents as well as antioxidant enzyme activities. Apoptosis was assayed by the TUNEL technique, protein expression, and activity of caspase 3. The data show that MEL restores the intestinal Ca2+ absorption altered by MEN. In addition, MEL reversed the effects caused by MEN such as decrease in GSH levels, increase in the carbonyl content, alteration in mitochondrial membrane permeability, and enhancement of superoxide dismutase and catalase activities. Apoptosis triggered by MEN in the intestinal cells was arrested by MEL, as indicated by normalization of the mitochondrial membrane permeability, caspase 3 activity, and DNA fragmentation. In conclusion, MEL reverses the inhibition of intestinal Ca2+ absorption produced by MEN counteracting oxidative stress and apoptosis. These findings suggest that MEL could be a potential drug of choice for the reversal of impaired intestinal Ca2+ absorption in certain gut disorders that occur with oxidative stress and apoptosis. PMID- 24234420 TI - Chemopreventive effects of resveratrol in a rat model of cerulein-induced acute pancreatitis. AB - In the past decades, a greater understanding of acute pancreatitis has led to improvement in mortality rates. Nevertheless, this disease continues to be a health care system problem due to its economical costs. Future strategies such as antioxidant supplementation could be very promising, regarding to beginning and progression of the disease. For this reason, this study was aimed at assessing the effect of exogenous administration of resveratrol during the induction process of acute pancreatitis caused by the cholecystokinin analog cerulein in rats. Resveratrol pretreatment reduced histological damage induced by cerulein treatment, as well as hyperamylasemia and hyperlipidemia. Altered levels of corticosterone, total antioxidant status, and glutathione peroxidase were significantly reverted to control levels by the administration of resveratrol. Lipid peroxidation was also counteracted; nevertheless, superoxide dismutase enzyme was overexpressed due to resveratrol pretreatment. Related to immune response, resveratrol pretreatment reduced pro-inflammatory cytokine IL-1beta levels and increased anti-inflammatory cytokine IL-10 levels. In addition, pretreatment with resveratrol in cerulein-induced pancreatitis rats was able to reverse, at least partially, the abnormal calcium signal induced by treatment with cerulein. In conclusion, this study confirms antioxidant and immunomodulatory properties of resveratrol as chemopreventive in cerulein-induced acute pancreatitis. PMID- 24234421 TI - The expression of Apoc3 mRNA is regulated by HNF4alpha and COUP-TFII, but not acute retinoid treatments, in primary rat hepatocytes and hepatoma cells. AB - Vitamin A status regulates obesity development, hyperlipidemia, and hepatic lipogenic gene expression in Zucker fatty (ZF) rats. The development of hyperlipidemia in acne patients treated with retinoic acid (RA) has been attributed to the induction of apolipoprotein C-III expression. To understand the role of retinoids in the development of hyperlipidemia in ZF rats, the expression levels of several selected RA-responsive genes in the liver and isolated hepatocytes from Zucker lean (ZL) and ZF rats were compared using real-time PCR. The Rarb and Srebp-1c mRNA levels are higher in the liver and isolated hepatocytes from ZF than ZL rats. The Apoc3 mRNA level is only higher in the isolated hepatocytes from ZF than ZL rats. To determine whether dynamic RA production acutely regulates Apoc3 expression, its mRNA levels in response to retinoid treatments or adenovirus-mediated overexpression of hepatocyte nuclear factor 4 alpha (HNF4alpha) and chicken ovalbumin upstream-transcription factor II (COUP-TFII) were analyzed. Retinoid treatments for 2-6 h did not induce the expression of Apoc3 mRNA. The overexpression of HNF4alpha or COUP-TFII induced or inhibited Apoc3 expression, respectively. We conclude that short-term retinoid treatments could not induce Apoc3 mRNA expression, which is regulated by HNF4alpha and COUP-TFII in hepatocytes. PMID- 24234422 TI - FMLP-, thapsigargin-, and H2O2-evoked changes in intracellular free calcium concentration in lymphocytes and neutrophils of type 2 diabetic patients. AB - Type 2 diabetic (T2DM) patients are immune-compromised having a higher susceptibility to infections and long-term complications in different parts of the body contributing to increased morbidity and mortality. A derangement in the homeostasis of intracellular free calcium concentration [Ca2+](i) is known to be associated with several diseases in the body including T2DM. Both neutrophils and lymphocytes play active protective roles in host immune response to infection showing impairment in microbicidal functions including phagocytosis and chemotaxis which are calcium-dependent processes. This study evaluated the process of [Ca2+]i mobilization from both neutrophils and lymphocytes taken from blood of both T2DM patients and healthy age-matched control subjects investigating the effect of N-formyl-methionyl-leucyl-phenylalanine (fMLP), thapsigargin (TG), and hydrogen peroxide (H2O2) on [Ca2+](i) homeostasis. This study employed isolated peripheral blood neutrophils and lymphocytes from 24 T2DM patients and 24 healthy volunteers. Either neutrophils or lymphocytes were stimulated separately with fMLP, TG, or H2O2. Induced changes in [Ca2+] in both neutrophils and lymphocytes were evaluated using spectrofluorometric methods. Stimulation of human neutrophils and lymphocytes with fMLP, TG, or H2O2 in the presence of [Ca2+]o resulted in significant decreases in [Ca2+](i) mobilization from T2DM patients compared with healthy controls. These data indicate that neutrophils and lymphocytes from T2DM patients are less responsive to calcium mobilizing agents compared with granulocytes from healthy controls and this is possibly due to the hyperglycemia. The results suggest that agonist-evoked decrease in [Ca2+](i) in immune cells might be one of the possible mechanisms of impaired immunity in diabetic patients. PMID- 24234423 TI - Peroxiredoxin 2 is upregulated in colorectal cancer and contributes to colorectal cancer cells' survival by protecting cells from oxidative stress. AB - Peroxiredoxin 2 (Prdx2) is a member of the peroxiredoxin family, which is responsible for neutralizing reactive oxygen species. Prdx2 has been found to be elevated in several human cancer cells and tissues, including colorectal cancer (CRC), and it influences diverse cellular processes involving cells' survival, proliferation, and apoptosis, which suggests a possible role for Prdx2 in the maintenance of cancer cell. However, the mechanism by which Prdx2 modulates CRC cells' survival is unknown. The current study aimed to determine the effect of elevated Prdx2 on CRC cells and to further understand the underlying mechanisms. The results of this study showed that Prdx2 was upregulated in CRC tissues compared with the matched noncancer colorectal mucosa tissues and that Prdx2 expression was positively associated with tumor metastasis and the TNM stage. In the LoVo CRC cell line, Prdx2 was upregulated at both the RNA and protein levels compared with the normal FHC colorectal mucosa cell line. In addition, the LoVo CRC cell line was significantly more resistant to hydrogen peroxide (H2O2) induced apoptosis because of a failure to activate pro-apoptotic pathways in contrast to Prdx2 knockdown cells. Suppression of Prdx2 using a lentiviral vector mediated Prdx2-specific shRNA in the LoVo cell line restored H2O2 sensitivity. Our results suggested that Prdx2 has an essential role in regulating oxidation induced apoptosis in CRC cells. Prdx2 may have potential as a therapeutic target in CRC. PMID- 24234424 TI - Postoperative refractive error following cataract surgery after the first attack of acute primary angle closure. AB - To investigate differences between preoperative target refraction and postoperative spherical equivalent refraction in eyes with the first attack of acute angle closure glaucoma before and after surgery. We retrospectively examined eyes of 36 patients who suffered the first attack of acute primary angle closure after undergoing cataract extraction and intraocular lens implant. We measured keratometric values (K1, K2) due to medical therapy for high ocular tension and the mean time interval until surgery. We compared the axial length, expected diopter, logMAR visual acuity, K1, K2, refractive spherical equivalent, and intraocular pressure (IOP) before and 6 months after surgery. The average preoperative IOP was 51.3 +/- 9.0 mmHg, but it decreased to 14.8 +/- 3.6 mmHg after surgery. No corneal edema was observed after surgery. The average axial length was 22.12 +/- 1.03 mm and there was no significant change in keratometric values, which were 7.72 +/- 0.33 mm (K1) and 7.51 +/- 0.31 mm (K2) before surgery and 7.67 +/- 0.33 mm (K1) and 7.49 +/- 0.29 mm (K2) after surgery. Similarly, no significant difference was observed in average preoperative target refractive error (-0.57 +/- 0.53 D) and average postoperative refractive spherical equivalent (-0.67 +/- 0.97 D). The inability to accurately determine preoperative refractive error due to corneal edema or other complications is a concern during the first attack of acute angle closure glaucoma. However, our results indicate that no differences should be expected between preoperative refractive error and postoperative refractive spherical equivalent. PMID- 24234425 TI - Third case of Candida dubliniensis endogenous endophthalmitis in North America: case report and review of the literature. AB - There are two previous reports of Candida dubliniensis endophthalmitis in North America. Here, we report a third case of C. dubliniensis endogenous endophthalmitis in a 31-year-old male patient who complained of left-sided decreased visual acuity. He had an associated mitral and tricuspid valve endocarditis, in the setting of intravenous drug use. Blood and sputum cultures were positive for C. dubliniensis. Fundoscopic examination was consistent with a fungal endophthalmitis. He was treated with fluconazole followed by intravenous liposomal amphotericin B for 6 weeks. C. dubliniensis is an important but rare cause of endophthalmitis in intravenous drug abusers. PMID- 24234426 TI - Postcaesarean open-heart surgery for Streptococcus sanguinis infective endocarditis. AB - A 33-week pregnant (gravida 3), 29-year-old woman was transferred for management of Streptococcus sanguinis infective endocarditis. A vegetation was present on the posterior leaflet of the mitral valve with moderate mitral regurgitation. On admission (day 1), the ultrasound examination revealed splenic abscesses and retarded intrauterine growth albeit with normal vessels. The fetal heart rate was 140 bpm. On day 11, the baby was delivered by Caesarean, and then the mother underwent tubal ligation followed by a mitral valve repair. The splenic abscess was treated with antibiotics. The woman was clinically stable and recovered uneventfully. This successful outcome was achieved by a strategic (optimal and sequential) timeline for selecting the mode of delivery and type of mitral valve correction. PMID- 24234427 TI - Ranibizumab in choroidal neovascularisation associated with ocular sarcoidosis. AB - An 81-year-old Caucasian man with a history of chronic bilateral panuveitis associated with sarcoidosis presented with visual acuity 1.0 LogMAR in the right and 0.5 LogMAR in the left eye. Following fluoroscein angiogram bilateral choroidal neovascular membrane was established. Treatment was initiated with a course of 3 monthly intravitreal injections of ranibizumab 0.5 mg in 0.05 mL bilaterally; oral prednisolone 30 mg/day on tapering doses controlled the ocular inflammation prior to the treatment with intravitreal injections. An additional two intravitreal ranibizumab injections were administered in the right eye. Fibrotic tissue in the posterior pole bilaterally was present on funduscopy following ranibizumab treatment. Visual acuity was LogMAR 1.6 in the right and 1.0 LogMAR in the left eye in 1 year follow-up. This case report summarises the issues of choroidal neovascularisation as a complication secondary to panuveitis associated with sarcoidosis and highlights the treatment of this complication with antivascular endothelial growth factor agents. PMID- 24234428 TI - Crossed cerebellar diaschisis: a radiological finding in status epilepticus not to miss. PMID- 24234429 TI - Refractory pruritus in primary biliary cirrhosis. AB - Pruritus is a major symptom of primary biliary cirrhosis, cholestatic autoimmune disease which affects mostly middle-age women. Often, it can be severe and refractory to multiple treatments, and mostly affecting the patient's health related quality of life. Intense pruritus can be itself an indication to liver transplantation, in extreme cases leading to suicide. Its physiopathology has not yet been fully elucidated, but recent studies added the elevation of autotaxin and lysophosphatidic acid to the group of classic mechanisms already linked to cholestatic pruritus. In this case report we illustrate how ultraviolet B phototherapy appears to successfully control severe pruritus and contribute to the healing of pruritic skin lesions caused by intense scratching. There is limited medical literature concerning this therapeutic approach on cholestatic pruritus, but we hope that further randomised controlled trials will successfully establish it as an effective treatment in the near future. PMID- 24234430 TI - Seizure as an initial presentation of human immunodeficiency virus: acute toxoplasmosis mimicking glioblastoma multiforme. AB - We present a case of a 46-year-old man with a history significant only for hypertension and depression that presented with a new onset seizure resulting from a right parietal lobe mass. Further evaluation determined the parietal mass to be central nervous system toxoplasmosis, which was the initial presentation of his underlying HIV/AIDS. This case provided a diagnostic challenge and demonstrates the importance of a thorough evaluation as it pertains to a newly diagnosed brain lesion. PMID- 24234431 TI - Small cell lung cancer presenting with a left iliac fossa mass. AB - We report a 59-year-old lifelong smoker with severe chronic obstructive pulmonary disease who presented with an acute onset 3-day history of left iliac fossa pain and abdominal distension. Clinical examination revealed a palpable mass in the left iliac fossa. The differential diagnosis was that of a diverticular abscess or colonic tumour. She subsequently underwent a CT scan which showed extensive metastatic liver disease from a primary lung tumour, with hepatomegaly abutting the anterior abdominal wall in the left iliac fossa. PMID- 24234432 TI - Successful treatment of acquired pure red cell aplasia with oral corticosteroids in a patient with B-cell CLL. AB - We present the case of a 57-year-old male patient diagnosed with chronic lymphoid leukaemia (CLL) B-cell type along with moderate anaemia. On follow-up investigations the aetiology of anaemia turned out to be pure red cell aplasia (PRCA) on trephine bone biopsy with an elevated serum erythropoietin level. The patient received blood transfusion support. He showed remarkable improvement on oral corticosteroids (prednisolone 60 mg/daily dose) with no further requirement of blood transfusion over next 3 months. However, when the dose of steroid was tapered down to 10 mg/day, the anaemia reappeared. An increase in the dose of steroid brought the haemoglobin level back to normal. Anaemia in CLL can be due to many reasons, of which PRCA is an uncommon association occurring in only around 1% of patients with CLL and usually refractory to the conventional treatment with steroids. This PRCA secondary to CLL is considered to be immune in origin and a response to combination of immunosuppressive therapy such as steroids, cyclosporine, rituximab is anticipated. Our case responded completely to oral steroids alone. PMID- 24234433 TI - Idiopathic sialectasis of the Stensen's duct treated with marsupialisation. AB - Sialectasis is an uncommon medical condition of the salivary glands. Conservative treatments of sialectasis include repeated aspiration, compression, dilation of the papilla and stent placement. This is the first reported case that we know of, using marsupialisation for distal sialectasis. Our case highlights the diagnostic and therapeutic challenges posed by sialectasis and demonstrates the efficacy of marsupialisation for distally based sialectasis when conservative treatments fail. PMID- 24234434 TI - Isolated cerebellar damage caused by carbon monoxide intoxication. PMID- 24234435 TI - Fibroepithelial polyp of the ureter. AB - A 36-year-old woman presented with haematuria and a bladder mass on ultrasonogram. Cystoscopy revealed a tumour, cauliflower in shape with smooth stalk coming out from the ureteric orifice. Stalk of the polyp was identified in proximal ureter by ureteroscopy. The mass was excised endoscopically. PMID- 24234437 TI - ClinVar: public archive of relationships among sequence variation and human phenotype. AB - ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations. PMID- 24234436 TI - ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription. AB - The remodeling of chromatin in the nucleolus is important for the control of ribosomal DNA (rDNA) transcription and ribosome biogenesis. Herein, we found that upstream binding factor (UBF) interacts with ESET, a histone H3K9 methyltransferase and is trimethylated at Lys (K) 232/254 by ESET. UBF trimethylation leads to nucleolar chromatin condensation and decreased rDNA transcriptional activity. UBF mutations at K232/254A and K232/254R restored rDNA transcriptional activity in response to ESET. Both ESET-DeltaSET mutant and knockdown of ESET by short hairpin RNA reduced trimethylation of UBF and resulted in the restoration of rDNA transcription. Atomic force microscopy confirmed that UBF trimethylated by ESET modulates the plasticity of nucleolar chromatin. We further demonstrated that UBF trimethylation at K232/254 by ESET deregulates rDNA transcription in a cell model of Huntington's disease. Together, our findings show that a novel epigenetic modification of UBF is linked to impaired rDNA transcription and nucleolar chromatin remodeling, which may play key roles in the pathogenesis of neurodegeneration. PMID- 24234438 TI - Developments in FINDbase worldwide database for clinically relevant genomic variation allele frequencies. AB - FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide. Each database record includes the population, ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related databases and the genetic variation together with its frequency in that population. Here, we report, in addition to the regular data content updates, significant developments in FINDbase, related to data visualization and querying, data submission, interrelation with other resources and a new module for genetic disease summaries. In particular, (i) we have developed new data visualization tools that facilitate data querying and comparison among different populations, (ii) we have generated a new FINDbase module, built around Microsoft's PivotViewer (http://www.getpivot.com) software, based on Microsoft Silverlight technology (http://www.silverlight.net), that includes 259 genetic disease summaries from five populations, systematically collected from the literature representing the documented genetic makeup of these populations and (iii) the implementation of a generic data submission tool for every module currently available in FINDbase. PMID- 24234439 TI - The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. AB - The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ~6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques. PMID- 24234440 TI - The evolution of the ribosome biogenesis pathway from a yeast perspective. AB - Ribosome biogenesis is fundamental for cellular life, but surprisingly little is known about the underlying pathway. In eukaryotes a comprehensive collection of experimentally verified ribosome biogenesis factors (RBFs) exists only for Saccharomyces cerevisiae. Far less is known for other fungi, animals or plants, and insights are even more limited for archaea. Starting from 255 yeast RBFs, we integrated ortholog searches, domain architecture comparisons and, in part, manual curation to investigate the inventories of RBF candidates in 261 eukaryotes, 26 archaea and 57 bacteria. The resulting phylogenetic profiles reveal the evolutionary ancestry of the yeast pathway. The oldest core comprising 20 RBF lineages dates back to the last universal common ancestor, while the youngest 20 factors are confined to the Saccharomycotina. On this basis, we outline similarities and differences of ribosome biogenesis across contemporary species. Archaea, so far a rather uncharted domain, possess 38 well-supported RBF candidates of which some are known to form functional sub-complexes in yeast. This provides initial evidence that ribosome biogenesis in eukaryotes and archaea follows similar principles. Within eukaryotes, RBF repertoires vary considerably. A comparison of yeast and human reveals that lineage-specific adaptation via RBF exclusion and addition characterizes the evolution of this ancient pathway. PMID- 24234441 TI - Translation rate is controlled by coupled trade-offs between site accessibility, selective RNA unfolding and sliding at upstream standby sites. AB - The ribosome's interactions with mRNA govern its translation rate and the effects of post-transcriptional regulation. Long, structured 5' untranslated regions (5' UTRs) are commonly found in bacterial mRNAs, though the physical mechanisms that determine how the ribosome binds these upstream regions remain poorly defined. Here, we systematically investigate the ribosome's interactions with structured standby sites, upstream of Shine-Dalgarno sequences, and show that these interactions can modulate translation initiation rates by over 100-fold. We find that an mRNA's translation initiation rate is controlled by the amount of single stranded surface area, the partial unfolding of RNA structures to minimize the ribosome's binding free energy penalty, the absence of cooperative binding and the potential for ribosomal sliding. We develop a biophysical model employing thermodynamic first principles and a four-parameter free energy model to accurately predict the ribosome's translation initiation rates for 136 synthetic 5' UTRs with large structures, diverse shapes and multiple standby site modules. The model predicts and experiments confirm that the ribosome can readily bind distant standby site modules that support high translation rates, providing a physical mechanism for observed context effects and long-range post transcriptional regulation. PMID- 24234442 TI - The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. AB - The centromere is a specific genomic region upon which the kinetochore is formed to attach to spindle microtubules for faithful chromosome segregation. To distinguish this chromosomal region from other genomic loci, the centromere contains a specific chromatin structure including specialized nucleosomes containing the histone H3 variant CENP-A. In addition to CENP-A nucleosomes, we have found that centromeres contain a nucleosome-like structure comprised of the histone-fold CENP-T-W-S-X complex. However, it is unclear how the CENP-T-W-S-X complex associates with centromere chromatin. Here, we demonstrate that the CENP T-W-S-X complex binds preferentially to ~ 100 bp of linker DNA rather than nucleosome-bound DNA. In addition, we find that the CENP-T-W-S-X complex primarily binds to DNA as a (CENP-T-W-S-X)2 structure. Interestingly, in contrast to canonical nucleosomes that negatively supercoil DNA, the CENP-T-W-S-X complex induces positive DNA supercoils. We found that the DNA-binding regions in CENP-T or CENP-W, but not CENP-S or CENP-X, are required for this positive supercoiling activity and the kinetochore targeting of the CENP-T-W-S-X complex. In summary, our work reveals the structural features and properties of the CENP-T-W-S-X complex for its localization to centromeres. PMID- 24234444 TI - CollecTF: a database of experimentally validated transcription factor-binding sites in Bacteria. AB - The influx of high-throughput data and the need for complex models to describe the interaction of prokaryotic transcription factors (TF) with their target sites pose new challenges for TF-binding site databases. CollecTF (http://collectf.umbc.edu) compiles data on experimentally validated, naturally occurring TF-binding sites across the Bacteria domain, placing a strong emphasis on the transparency of the curation process, the quality and availability of the stored data and fully customizable access to its records. CollecTF integrates multiple sources of data automatically and openly, allowing users to dynamically redefine binding motifs and their experimental support base. Data quality and currency are fostered in CollecTF by adopting a sustainable model that encourages direct author submissions in combination with in-house validation and curation of published literature. CollecTF entries are periodically submitted to NCBI for integration into RefSeq complete genome records as link-out features, maximizing the visibility of the data and enriching the annotation of RefSeq files with regulatory information. Seeking to facilitate comparative genomics and machine learning analyses of regulatory interactions, in its initial release CollecTF provides domain-wide coverage of two TF families (LexA and Fur), as well as extensive representation for a clinically important bacterial family, the Vibrionaceae. PMID- 24234443 TI - RNA-dependent dynamic histone acetylation regulates MCL1 alternative splicing. AB - Histone deacetylases (HDACs) and lysine acetyltransferases (KATs) catalyze dynamic histone acetylation at regulatory and coding regions of transcribed genes. Highly phosphorylated HDAC2 is recruited within corepressor complexes to regulatory regions, while the nonphosphorylated form is associated with the gene body. In this study, we characterized the nonphosphorylated HDAC2 complexes recruited to the transcribed gene body and explored the function of HDAC-complex mediated dynamic histone acetylation. HDAC1 and 2 were coimmunoprecipitated with several splicing factors, including serine/arginine-rich splicing factor 1 (SRSF1) which has roles in alternative splicing. The co-chromatin immunoprecipitation of HDAC1/2 and SRSF1 to the gene body was RNA-dependent. Inhibition of HDAC activity and knockdown of HDAC1, HDAC2 or SRSF1 showed that these proteins were involved in alternative splicing of MCL1. HDAC1/2 and KAT2B were associated with nascent pre-mRNA in general and with MCL1 pre-mRNA specifically. Inhibition of HDAC activity increased the occupancy of KAT2B and acetylation of H3 and H4 of the H3K4 methylated alternative MCL1 exon 2 nucleosome. Thus, nonphosphorylated HDAC1/2 is recruited to pre-mRNA by splicing factors to act at the RNA level with KAT2B and other KATs to catalyze dynamic histone acetylation of the MCL1 alternative exon and alter the splicing of MCL1 pre-mRNA. PMID- 24234445 TI - Transcription factor abundance controlled by an auto-regulatory mechanism involving a transcription start site switch. AB - A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5' untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level. PMID- 24234446 TI - The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation. AB - The replicative mini-chromosome-maintenance 2-7 (MCM2-7) helicase is loaded in Saccharomyces cerevisiae and other eukaryotes as a head-to-head double-hexamer around origin DNA. At first, ORC/Cdc6 recruits with the help of Cdt1 a single MCM2-7 hexamer to form an 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex. Then, on ATP hydrolysis and Cdt1 release, the 'initial' complex is transformed into an ORC/Cdc6/MCM2-7 (OCM) complex. However, it remains unclear how the OCM is subsequently converted into a MCM2-7 double-hexamer. Through analysis of MCM2-7 hexamer-interface mutants we discovered a complex competent for MCM2-7 dimerization. We demonstrate that these MCM2-7 mutants arrest during prereplicative complex (pre-RC) assembly after OCM formation, but before MCM2-7 double-hexamer assembly. Remarkably, only the OCM complex, but not the 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex, is competent for MCM2-7 dimerization. The MCM2-7 dimer, in contrast to the MCM2-7 double-hexamer, interacts with ORC/Cdc6 and is salt-sensitive, classifying the arrested complex as a helicase-loading intermediate. Accordingly, we found that overexpression of the mutants cause cell cycle arrest and dominant lethality. Our work identifies the OCM complex as competent for MCM2-7 dimerization, reveals MCM2-7 dimerization as a limiting step during pre-RC formation and defines critical mechanisms that explain how origins are licensed. PMID- 24234447 TI - UniCarbKB: building a knowledge platform for glycoproteomics. AB - The UniCarb KnowledgeBase (UniCarbKB; http://unicarbkb.org) offers public access to a growing, curated database of information on the glycan structures of glycoproteins. UniCarbKB is an international effort that aims to further our understanding of structures, pathways and networks involved in glycosylation and glyco-mediated processes by integrating structural, experimental and functional glycoscience information. This initiative builds upon the success of the glycan structure database GlycoSuiteDB, together with the informatic standards introduced by EUROCarbDB, to provide a high-quality and updated resource to support glycomics and glycoproteomics research. UniCarbKB provides comprehensive information concerning glycan structures, and published glycoprotein information including global and site-specific attachment information. For the first release over 890 references, 3740 glycan structure entries and 400 glycoproteins have been curated. Further, 598 protein glycosylation sites have been annotated with experimentally confirmed glycan structures from the literature. Among these are 35 glycoproteins, 502 structures and 60 publications previously not included in GlycoSuiteDB. This article provides an update on the transformation of GlycoSuiteDB (featured in previous NAR Database issues and hosted by ExPASy since 2009) to UniCarbKB and its integration with UniProtKB and GlycoMod. Here, we introduce a refactored database, supported by substantial new curated data collections and intuitive user-interfaces that improve database searching. PMID- 24234448 TI - Inverse regulation of Fe- and Ni-containing SOD genes by a Fur family regulator Nur through small RNA processed from 3'UTR of the sodF mRNA. AB - Superoxide dismutases (SODs) are widely distributed enzymes that convert superoxides to hydrogen peroxide and molecular oxygen, using various metals as cofactors. Many actinobacteria contain genes for both Ni-containing (sodN) and Fe containing (sodF) SODs. In Streptomyces coelicolor, expression of the sodF and sodN genes is inversely regulated by nickel-specific Nur, a Fur-family regulator. With sufficient nickel, Nur directly represses sodF transcription, while inducing sodN indirectly. Bioinformatic search revealed that a conserved 19-nt stretch upstream of sodN matches perfectly with the sodF downstream sequence. We found that the sodF gene produced a stable small-sized RNA species (s-SodF) of ~ 90 nt that harbors the anti-sodN sequence complementary to sodN mRNA from the 5'-end up to the ribosome binding site. Absence of nearby promoters and sensitivity to 5' phosphate-specific exonuclease indicated that the s-SodF RNA is a likely processed product of sodF mRNA. The s-SodF RNA caused a significant decrease in the half-life of the sodN mRNA. Therefore, Nur activates sodN expression through inhibiting the synthesis of sodF mRNA, from which inhibitory s-SodF RNA is generated. This reveals a novel mechanism by which antagonistic regulation of one gene is achieved by small RNA processed from the 3'UTR of another gene's mRNA. PMID- 24234449 TI - FlyBase 102--advanced approaches to interrogating FlyBase. AB - FlyBase (http://flybase.org) is the leading website and database of Drosophila genes and genomes. Whether you are using the fruit fly Drosophila melanogaster as an experimental system or wish to understand Drosophila biological knowledge in relation to human disease or to other model systems, FlyBase can help you successfully find the information you are looking for. Here, we demonstrate some of our more advanced searching systems and highlight some of our new tools for searching the wealth of data on FlyBase. The first section explores gene function in FlyBase, using our TermLink tool to search with Controlled Vocabulary terms and our new RNA-Seq Search tool to search gene expression. The second section of this article describes a few ways to search genomic data in FlyBase, using our BLAST server and the new implementation of GBrowse 2, as well as our new FeatureMapper tool. Finally, we move on to discuss our most powerful search tool, QueryBuilder, before describing pre-computed cuts of the data and how to query the database programmatically. PMID- 24234450 TI - Cycling of the E. coli lagging strand polymerase is triggered exclusively by the availability of a new primer at the replication fork. AB - Two models have been proposed for triggering release of the lagging strand polymerase at the replication fork, enabling cycling to the primer for the next Okazaki fragment--either collision with the 5'-end of the preceding fragment (collision model) or synthesis of a new primer by primase (signaling model). Specific perturbation of lagging strand elongation on minicircles with a highly asymmetric G:C distribution with ddGTP or dGDPNP yielded results that confirmed the signaling model and ruled out the collision model. We demonstrated that the presence of a primer, not primase per se, provides the signal that triggers cycling. Lagging strand synthesis proceeds much faster than leading strand synthesis, explaining why gaps between Okazaki fragments are not found under physiological conditions. PMID- 24234451 TI - The MIntAct project--IntAct as a common curation platform for 11 molecular interaction databases. AB - IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org). PMID- 24234452 TI - Analysis of the mechanism of nucleosome survival during transcription. AB - Maintenance of nucleosomal structure in the cell nuclei is essential for cell viability, regulation of gene expression and normal aging. Our previous data identified a key intermediate (a small intranucleosomal DNA loop, O-loop) that is likely required for nucleosome survival during transcription by RNA polymerase II (Pol II) through chromatin, and suggested that strong nucleosomal pausing guarantees efficient nucleosome survival. To evaluate these predictions, we analysed transcription through a nucleosome by different, structurally related RNA polymerases and mutant yeast Pol II having different histone-interacting surfaces that presumably stabilize the O-loop. The height of the nucleosomal barrier to transcription and efficiency of nucleosome survival correlate with the net negative charges of the histone-interacting surfaces. Molecular modeling and analysis of Pol II-nucleosome intermediates by DNase I footprinting suggest that efficient O-loop formation and nucleosome survival are mediated by electrostatic interactions between the largest subunit of Pol II and core histones. PMID- 24234453 TI - Single-molecule characterization of Fen1 and Fen1/PCNA complexes acting on flap substrates. AB - Flap endonuclease 1 (Fen1) is a highly conserved structure-specific nuclease that catalyses a specific incision to remove 5' flaps in double-stranded DNA substrates. Fen1 plays an essential role in key cellular processes, such as DNA replication and repair, and mutations that compromise Fen1 expression levels or activity have severe health implications in humans. The nuclease activity of Fen1 and other FEN family members can be stimulated by processivity clamps such as proliferating cell nuclear antigen (PCNA); however, the exact mechanism of PCNA activation is currently unknown. Here, we have used a combination of ensemble and single-molecule Forster resonance energy transfer together with protein-induced fluorescence enhancement to uncouple and investigate the substrate recognition and catalytic steps of Fen1 and Fen1/PCNA complexes. We propose a model in which upon Fen1 binding, a highly dynamic substrate is bent and locked into an open flap conformation where specific Fen1/DNA interactions can be established. PCNA enhances Fen1 recognition of the DNA substrate by further promoting the open flap conformation in a step that may involve facilitated threading of the 5' ssDNA flap. Merging our data with existing crystallographic and molecular dynamics simulations we provide a solution-based model for the Fen1/PCNA/DNA ternary complex. PMID- 24234455 TI - Development of enzyme technology and enzyme engineering in China. AB - Enzymes have been utilized in China for thousands of years for the production of various foods and alcoholic beverages. Today China manufactures and uses enzymes for not only the traditional areas of application, but is expanding the use of enzymes for a variety of nonfood areas. This report describes the present state of the art of enzyme manufacture and application in China today. PMID- 24234456 TI - Recycling of NADP(+) using immobilizedE. coli and glucose-6-phosphate dehydrogenase. AB - Recycling of NADP(+) using immobilized wholeEscherichia coli cells as source of respiratory chain, glucose-6-phosphate, and soluble yeast glucose-6-phosphate dehydrogenase (1.1.1.49) is described. NADP(+) was recycled more than 10-fold.We demonstrated NADPH respiration at pH 5.8 inE. coli membrane vesicles. The respiratory chain was involved most probably in NADPH oxidation. 1. The respiratory activity is localized at the level of the inner bacterial membrane. The active site for NADPH facing the cytoplasm. 2. NADPH respiration is inhibited by 10 mM cyanide, similar to the conditions of inhibition of NADH respiration. 3. NADPH dehydrogenase activity seems to be the limiting step of the respiratory chain:K M for NADPH respiration and NADPH dehydrogenase activity are similar. The pH optima for these two activities are also comparable (around pH 5.8). Furthermore, the following properties are rather in favor of a common NADH dehydrogenase and NADPH dehydrogenase activity (1.6.99.2). o| li](1)|At saturating concentrations of NADH and NADPH, neither respiration nor dehydrogenase activities were additive. li](2)|Similar heat inactivation kinetics were observed for NADH and NADPH dehydrogenase-activity.Protection against heat inactivation was obtained for the two activities with NAD(+), NADP(+), NADH, and NADPH.All these results suggested the possibility of recycling of NADP(+) under similar conditions to those previously described for NAD(+) (Burstein et al., 1981). It becomes thus possible to use various NAD(+) and NADP(+)-dependent dehydrogenases in enzyme technology. PMID- 24234454 TI - Characterization of the interaction between protein Snu13p/15.5K and the Rsa1p/NUFIP factor and demonstration of its functional importance for snoRNP assembly. AB - The yeast Snu13p protein and its 15.5K human homolog both bind U4 snRNA and box C/D snoRNAs. They also bind the Rsa1p/NUFIP assembly factor, proposed to scaffold immature snoRNPs and to recruit the Hsp90-R2TP chaperone complex. However, the nature of the Snu13p/15.5K-Rsa1p/NUFIP interaction and its exact role in snoRNP assembly remained to be elucidated. By using biophysical, molecular and imaging approaches, here, we identify residues needed for Snu13p/15.5K-Rsa1p/NUFIP interaction. By NMR structure determination and docking approaches, we built a 3D model of the Snup13p-Rsa1p interface, suggesting that residues R249, R246 and K250 in Rsa1p and E72 and D73 in Snu13p form a network of electrostatic interactions shielded from the solvent by hydrophobic residues from both proteins and that residue W253 of Rsa1p is inserted in a hydrophobic cavity of Snu13p. Individual mutations of residues in yeast demonstrate the functional importance of the predicted interactions for both cell growth and snoRNP formation. Using archaeal box C/D sRNP 3D structures as templates, the association of Snu13p with Rsa1p is predicted to be exclusive of interactions in active snoRNPs. Rsa1p and NUFIP may thus prevent premature activity of pre-snoRNPs, and their removal may be a key step for active snoRNP production. PMID- 24234457 TI - Biotinyl-glucose-6-phosphate dehydrogenase preparation, kinetics, and modulation by avidin. AB - The kinetics of free glucose-6-phosphate dehydrogenase (G-6-PDH), biotinylated G 6-PDH, and biotinylated G-6-PDH complexed with avidin were investigated. The kinetics of the free enzyme were consistent with a sequential rather than a ping pong mechanism. The kinetics of the biotinylated enzyme were similar to that of the free enzyme, but the kinetic constants were different; theK m value for NADP was halved, whereas theK m for G-6-P decreased only slightly. In the presence of avidin, theK m of biotinylated G-6-PDH for G-6-P nearly doubled whereas theK m for NADP did not change significantly. Avidin complexed with biotinylated G-6-PDH inhibited the enzyme from acting. Based upon these reactions, it was possible to devise assays for either free biotin or free avidin using biotinylated G-6-PDH as the indicator enzyme. Concentrations of biotin between 40 and 60 mg/mL, or of 25 95 MUg/mL of avidin could be measured within 2 min through the use of biotinylated G-6-PDH. PMID- 24234458 TI - Inhibition of cellulases by impurities in Steam-Exploded wood. AB - Steam explosion of hardwood chips produces impurities that reduce the activity and stability of cellulases. Washing the exploded wood with water removes the inhibitors and permits hydrolysis equivalent to that with purified cellulose. PMID- 24234459 TI - Immunoenzymatic determination of antibody-bound soluble antigens ofTrypanosoma cruzi. AB - Anti-Major Cathodic Antigen (MCA) monospecific immunoglobulins ofT. cruzi have been used for the preparation of polyamide-linked immunoadsorbents. A high proportion of serologically positive patients with Chagas disease show the presence of a soluble antigen complexed with human immunoglobulins, which complex binds to those immunoadsorbents as determined by a double sandwich reaction and a peroxidase final determination. PMID- 24234460 TI - Properties of bacterial luciferase/NADH : FMN oxidoreductase and firefly luciferase immobilized onto sepharose. AB - NADH : FMN oxidoreductase and bacterial luciferase have been efficiently coimmobilized onto Sepharose 4B. This luminescent immobilized enzyme system can be used to assay NADH. The assay is rapid and sensitive with a lower limit of detection of 0.2 pmol/assay tube. The intra-assay precision was 3.5% at 2 * 10( 5) M and 5.8% at 2 * 10(-6) M NADH. Light intensity was proportional to NADH concentration from 0.2 to 1000 pmol. Added serum and certain dehydrogenases were found to be inhibitory; however, inhibition could be eliminated by a combination of heat treatment and dilution.Firefly luciferase has also been immobilized onto both Sepharose 4B and CL 6B. The detection limit for ATP using this immobilized enzyme was 0.2 pmol and the assay was linear from 0.2 to 2000 pmol. The intra assay precision was 4.8% at 2 * 10(-4) M and 3.2% at 1 * 10(-5) M ATP.The immobilized enzymes remained fully active when rapidly frozen in the presence of glycerol and DTT. Such preparations could be stored for at least two months with no loss of activity. A variety of different compounds were used to block any remaining reactive groups on the Sepharose following immobilization of the enzymes. Glycine, 2-aminoethanol, and ethylenediamine were examined. The preparations where ethylenediamine was used as a blocking agent exhibited better activity and stability than the others. PMID- 24234463 TI - Chronic toxicity: How can we measure it? PMID- 24234461 TI - Molar absorptivity and A1 cm (1%) values for proteins at selected wavelengths of the ultraviolet and visible regions. XXII. AB - The molar absorptivity and A1 cm (1%) values for 150 proteins are reported. The conditions under which these values were obtained and citations to the sources of the data are also provided. PMID- 24234462 TI - Patents and literature. PMID- 24234464 TI - Modelling the accumulation of hydrophobic organic chemicals in earthworms : Application of the equilibrium partitioning theory. AB - In this paper a method is developed which can be used to estimate the body burden of organic hydrophobic chemicals in earthworms. In contrast to the equilibrium partitioning theory, two routes of uptake are incorporated: uptake from interstitial water and dietary uptake. Although many uncertainties still remain, calculations show that for earthworms steady state body burdens are mainly determined by uptake from interstitial water. Under most circumstances, the contribution of dietary uptake is small, except for hydrophobic chemicals (log Kow > 5) in soils with a high organic matter (OM) content of ~ 20 %. Under those conditions, estimates of the steady state body burden calculated with the equilibrium partitioning model, in which only uptake from interstitial water is taken into account, might result in a small underestimation of the real body burden of chemicals in earthworms. PMID- 24234465 TI - Monitoring behavioural responses to metals inGammarus pulex (L.) (Crustacea) with impedance conversion. AB - An impedance conversion technique was used to study the behaviour ofGammarus pulex (L.) exposed to acutely toxic concentrations of Pb (0.01, 0.05, 0.1 and 0.5 mg Pb l(-1)) and to field concentrations of Cu ( <= 0.05 mg Cu l(-1)). Initial stress responses were studied during short-term exposure (1 h) and sublethal toxic effects were monitored during 7 (Pb) and 35 days (Cu), respectively.Exposure to Pb caused 30 % mortality and resulted in a bioconcentration factor (BCF) of 2700 at 0.5 mg Pb l(-1) after 168 h. Exposure to Cu polluted stream water caused no mortality within 35 days and uptake was low (BCF 5.8).Gammarus pulex reacted with initial stress responses to metal exposure within 30 min. (Cu) or 1 h (Pb). The reactions consisted of increased ventilation and decreased locomotion.Sublethal concentrations of Pb and Cu caused toxic effects on the behaviour of G.pulex after several days of exposure, consisting of increased ventilation and decreased locomotion.Impedance conversion is an appropriate method for detecting stress responses to metals and can be used in "early warning" biomonitoring systems as well as for acute and chronic behavioural toxicity testing. PMID- 24234466 TI - Lipid-Filled semipermeable membrane devices and mussels as samplers of organochlorine compounds in lake water. AB - Semipermeable membrane sampling devices (SPMDs) and caged lake mussels (Anodonta piscinalis) were simultaneously deployed at four lake watercourse sites in Central Finland four weeks in August 1992. This study was part of the regular annual monitoring of the organochlorine compounds (OCC) in pulp-mill recipient watercourses of Finland with bivalves. Chlorohydrocarbons (CHCs), chlorophenol compounds (PCPs), chloroanisoles (PCAs) and chloroveratroles (PCVs) were analyzed from lipid extract of mussels and from the synthetic triolein lipid of the SPMDs. Hexane-diethyl ether (9:1, v/v) dialysis using polyethylene membrane was applied in dean up of the SPMD lipids and, for comparison, to six sets of the mussel fat. Dialysis recovered CHCs but not PCPs from the mussel fat. CHCs, PCPs, PCAs and PCVs were all recovered in dialysis of the SPMD lipid. Handling of SPMDs in the transport and deployment operations caused significant OCC contamination for the blank SPMDs. Similar trends were revealed in the OCC profiles for mussels ans SPMDs. An exception was the lack of PCPs appearing in SPMDs that did appear in mussels and in a complementary manner the appearance of the PCAs and PCVs in SPMDs. PMID- 24234467 TI - Skin component may protect fishes from ultraviolet-B radiation. AB - We observed a large peak of absorbance when methanol extracts of dorsal skin from four species of fish were scanned in a spectro-photometer. There appeared to be a direct relation between the amount of this skin component and the period of time in which each species of fish developed UVB-induced sunburn. PMID- 24234468 TI - Compound dependence of the relationship log K(ow) and log BCF L : A comparison between chlorobenzenes (CBs) for rainbow trout and polycyclic aromatic hydrocarbons (PAHs) forDaphnia. AB - Linear relatinships between log bioconcentration factor (BCF) and log K(ow) for a variety of compounds have been reported many times in the literature. Analysis of the thermodynamics of the two partition processes has, however, shown that they are not analogous and that linear relationships can be expected to have different slopes for structurally unrelated compounds. In this study a set of literature lipid normalized BCF (BCFL) values of chlorbenzenes (CBs) for rainbow trout and polycyclic aromatic hydrocarbons (PAHs) forDaphnia was put together with literature Kow values. The slopes of the regression lines for log BCFL versus log Kow for the two groups of compounds proved to differ significantly in a statistical test using analysis of variance (ANOVA). The difference, which is of significance for estimates of BCFs in environmental modelling of these types of compounds, is explained by the differences in chemical structure of the two groups of compounds. PMID- 24234469 TI - Preface of the series. PMID- 24234470 TI - Exposure and hazard assessment within the life cycle impact assessment. PMID- 24234471 TI - Greenhouse effect of NOX. AB - Through various processes the nitrogen oxides (NOX) interact with trace gases in the troposphere and stratosphere which do absorb in the spectral range relevant to the greenhouse effect (infrared wavelengths). The net effect is an enhancement of the greenhouse effect. The catalytic role of NOX in the production of tropospheric ozone provides the most prominent contribution. The global waming potential is estimated as GWP (NOX = 30 - 33 and 7 - 10 for the respective time horizons of 20 and 100 years, and is thereby comparable to that of methane. NOX emissions in rural areas of anthropogenically influenced regions, or those in the vicinity of the txopopause caused by air traffic, cause the greenhouse effectivity to be substantially more intense. We estimate an additional 5-23 % for Germany's contribution to the anthropogenic greenhouse effect as a result of the indirect greenhouse effects stemming from NOX. Furthermore, a small and still inaccurately defined amount of the deposited NOX which has primarily been converted into nitrates is again released from the soil into the atmosphere in the form of the long-lived greenhouse gas nitrous oxide (N2O). Thus, anthropogenically induced NOX emissions contribute to enhanced greenhouse effect and to stratospheric ozone depletion in the time scale of more than a century. PMID- 24234472 TI - Dioxins and related compounds: Status and regulatory aspects. AB - Several countries have put much effort in dioxin research programmes with the aim to assess the risks of dioxin exposure, to identify dioxin sources and to quantify their contribution to environmental emissions and human exposure. In this review, the accent has been put on: sources of dioxins and their contribution to the total dioxin emissions, sources of human exposure and their contribution to exposure and measures to reduce emission and exposure. The information from countries with existing dioxin regulations is reviewed and compared. Uncertainties which hamper comparability of data are indicated. Results of measures and expectations for the near future are presented. PMID- 24234473 TI - Environmental sciences education at the Swiss Federal Institute of Technology (ETH) Zurich and at other Swiss universities. PMID- 24234474 TI - K. C. Jones: Observations of long-term air-soil exchange of organic contaminants, ESPR 1 (3), 172-177(1994). PMID- 24234475 TI - Z. Jaworowski: Ancient atmosphere - Validity of ice records ESPR 1 (3) 161-171 (1994). PMID- 24234476 TI - International Workshop on Biological UV-Dosimetry- Budapest (Hungary), November 29-Dezember 3, 1994. PMID- 24234479 TI - Basal cell carcinoma metastatic to parotid gland. AB - Metastasis from basal cell carcinoma of the skin is very rare with cases being documented in the lymph nodes, lung, bone and parotid gland. The main histopathological differential diagnosis is the locally arising basal cell adenocarcinoma from which it is difficult to distinguish by morphology and routine immunohistochemistry. Approximately 85 % of all reported metastatic basal cell carcinomas arise in the head and neck region. Here we present a case of basal cell carcinoma of the skin of the left lateral canthus of the eye which metastasized to the intraparotid lymph nodes with infiltration of the adjacent parotid parenchyma. More awareness and vigilance is required on the part of the reporting pathologist to consider metastasis in the presence of a parotid tumour. Features favouring metastasis include history of primary cutaneous basal cell carcinoma, histological similarity to the primary lesion and absence of any demonstrable direct extension from the skin lesion. We also review the literature on metastatic basal cell carcinoma and discuss the need for adequate follow up in high risk patients. PMID- 24234480 TI - Editorial introduction. PMID- 24234481 TI - Recommendations for standardized human pedigree nomenclature. AB - The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant inconsistencies in the usage of common pedigree symbols representing situations such as pregnancy, termination of pregnancy, miscarriage, and adoption, as well as less common scenarios such as pregnancies conceived through assisted reproductive technologies. The Pedigree Standardization Task Force (PSTF) was organized through the Professional Issues Committee of the National Society of Genetic Counselors, to establish recommendations for universal standards in human pedigree nomenclature. Nomenclature was chosen based on current usage, consistency among symbols, computer compatibility, and the adaptability of symbols to reflect the rapid technical advances in human genetics. Preliminary recommendations were presented for review at three national meetings of human genetic professionals and sent to >100 human genetic professionals for review. On the basis of this review process, the recommendations of the PSTF for standardized human pedigree nomenclature are presented here. By incorporating these recommendations into medical genetics professional training programs, board examinations, genetic publications, and pedigree software, the adoption of uniform pedigree nomenclature can begin. Usage of standardized pedigree nomenclature will reduce the chances for incorrect interpretation of patient and family medical and genetic information. It may also improve the quality of patient care provided by genetic professionals and facilitate communication between researchers involved with genetic family studies. PMID- 24234482 TI - An assessment of teratology training provided by masters level genetic counseling programs. AB - The increasing demand in the clinical genetics setting for information about teratogen exposures has created a need for genetic counselors to have the capabilities to appropriately address patient concerns. In order to assess how training in teratogen counseling is currently being conducted, the GLaRGG Teratogen Subcommittee surveyed all 17 genetic counseling training programs in North America in September 1993. Information was obtained from training programs about coursework, resources, and clinical training. In addition, each training program was asked to provide information about how their teratogen training needs could better be met. While all programs responded that some information in their coursework applicable to teratogen counseling was provided, there was wide variation in the amount of time devoted to this topic. The programs also greatly differed in the provision of clinical training in teratogen counseling. For both coursework and clinical work, genetic counselors were the main trainers in teratogen counseling. In spite of this, fewer than 25% of training programs have a defined teratogen clinical rotation. Data from the survey are discussed and recommendations presented. PMID- 24234483 TI - Abstracts of papers presented at the Fourteenth Annual Education Conference : Conditions that affect adults. PMID- 24234484 TI - The importance of adult Hediste (Nereis) diversicolor in managing heavy metal pollution in shores and estuaries. AB - The main aim of the toxicity test is to be able to measure toxicity in organisms, and therefore to assess whether a nationally or internationally preset standard is met. LC50 values (median lethal concentration that kills 50% of the population at a given time) or LT50 values (median lethal time in which 50% of the test species died) provide useful information for risk assessment. However, extrapolating laboratory data to actual field conditions is difficult because of changing environmental factors like temperature and salinity. LC50 copper data for Hediste diversicolor treated multifactorially show the plasticity of the worm to environmental variables. Increasing temperature, 12 to 22 degrees C, and increasing salinity, 7.6 to 30.50/00 reduced toxicity of copper to the worms without sediment. In the presence of sediment increasing temperature and increasing salinity increased toxicity of copper to the worms. PMID- 24234485 TI - Estimation of nonpoint source loadings with data obtained from limited sampling programs. AB - The feasibility of estimating nonpoint source loadings with data obtained from limited sampling programs was analyzed in conjunction with a study of sediment and nutrient loadings in a Swedish river basin. The study showed that different loading estimation methods can yield significantly different results, even if sampling during events (e.g. peak flows) occurs. This was particularly true for the temporal distribution of the estimated loadings. The estimated spatial distribution of loadings in the monitored subbasins was more independent of the applied estimation technique. Theoretical calculations showed that sampling strategies with evenly spaced sampling intervals may systematically over- or underestimate the true loading.The study basin was characterized by a pronounced snowmelt period and partly erosion-controlled nutrient loadings. Guidelines for the estimation of nonpoint loadings in such basins are summarized in a matrix. Factors influencing the choice of estimation method include the characteristics of the collected data, the relative influence of point sources, and the desired detail of loading estimates. Possible correlations between flow and concentration, and the presence of extreme events (and whether or not the events were sampled), also determine the appropriateness of the different methods. PMID- 24234486 TI - The lognormal distribution, environmental data, and radiological monitoring. AB - The lognormal distribution has become a common choice to represent intrinsically positive and often highly skewed environmental data in statistical analysis. However the implications of its use are often not carefully considered. With an emphasis on radiological monitoring applications, this paper reviews what assuming lognormality means in terms of data analysis and interpretation. The relationship of using normal theory methods on log transformed data to multiplicative errors and hypothesis testing in the original scale is also discussed. PMID- 24234487 TI - Effects of eutrophication and organic loading on the occurrence of profundal harpacticoids in a lake in southern Finland. AB - Harpacticoids made up 19 and 30% of the meiobenthos proper by number and 39 and 55% by biomass at maximum depths and a depth of 20 m, respectively, in Lake Paijanne. Harpacticoids accounted for higher proportions of the total meiobenthos in oligotrophic and unpolluted areas than in polluted areas. Seven species were identified, with Canthocamptus staphylinus confined to semi-lotic areas influenced by organic pollution from a pulp mill. Other species exhibited somewhat different distributions in oligotrophic and mesotrophic areas. Harpacticoid densities were most closely correlated with oxygen content and phytoplankton biomass, and correlations with environmental values were closer at maximum depths than at 20 m. Attheyella crassa densities in the deepest zone had most marked negative correlation with total phosphorus, phytoplankton biomass, dissolved organic matter and organic sedimentation, while Paracamptus schmeili had the closest positive correlation with oxygen content. High densities of these species could be classified as an indicator of oligotrophic conditions. Similar correlations, although weaker, were evident for Bryocamptus minutus and still weaker for Bryocamptus echinatus and Moraria brevipes. Clustering of the stations based on harpacticoid abundances gave a similar result to clustering based on environmental data, particularly in the 20 m zone. PMID- 24234488 TI - A comparison of sampling techniques and summary indices for assessment of water quality in the Yamaska River, Quebec, based on benthic macroinvertebrates. AB - The Yamaska River drainage basin in Quebec, Canada, is intensively farmed and heavily polluted with poorly treated domestic and industrial wastes. We investigated the responses of the resident and colonizing components of the benthic macroinvertebrate community to municipal/industrial versus agricultural pollution in the basin, and evaluated the performances of seven diversity and biotic indices for assessing water quality. Samples of riffle-dwelling, infaunal and colonizing invertebrates were collected from 13 stations representing a wide range of types and degrees of pollution using Surber, scoop and artificial substrate samplers. The data were summarized using the indices S (number of taxa), N (number of individuals), H' (Shannon-Wiener's diversity index), D (Simpson's diversity index), BBI (Belgian Biotic Index), TBI (a modification of Hilsenhoff's Biotic Index), % CHIR (percentage of arthropods consisting of Chironomidae) and %OLIGO (percentage of total organisms consisting of Oligochaeta). Different components of the community generated somewhat different assessments and were, therefore, complementary. Community composition, expressed as the percentage of individuals contributed by major taxonomic groups, reflected the kinds of stresses at a station more consistently than did any of the indices. S and TBI came closest to ranking control, agricultural and municipal/industrial sites in accordance with our a priori classification, both between months and among sampling methods. %OLIGO usually separated municipal/industrial sites from control sites. Other indices were found to be less sensitive, accurate or temporally stable, or were otherwise inappropriate for use with certain sampling methods or for certain types of pollution. With most of our samples, all of the summary indices suggested that the impact of agricultural practices on stream ecosystems may be as severe as the impacts of municipal and industrial wastes. PMID- 24234490 TI - A Personal history of the early development of the flowing afterglow technique for ion-molecule reaction studies. AB - A personal perspective of the historical development of the flowing afterglow (FA) technique for measuring thermal energy ion-molecule reaction rate constants is presented. The technique was developed in the period starting in late 1962 in what was then the National Bureau of Standards in Boulder, Colorado. The motivation was primarily to obtain a quantitative understanding of the ion chemistry of the terrestrial ionosphere, a program that was substantially achieved. The thermal energy measurements were extended in temperature from 300 K to a range of 80 K-900 K and subsequently to a center-of-mass kinetic energy range up to ~ 2 eV with the introduction of a drift tube into the FA.The chemical versatility, in regard to both the ion and the neutral reactants measured, remains unequaled and FA systems are currently in widespread use around the world for a variety of chemical research programs. PMID- 24234489 TI - Seroadaptation among men who have sex with men: emerging research themes. AB - Seroadaptation describes a diverse set of potentially harm-reducing behaviors that use HIV status to inform sexual decision making. Men who have sex with men (MSM) in many settings adopt these practices, but their effectiveness at preventing HIV transmission is debated. Past modeling studies have demonstrated that serosorting is only effective at preventing HIV transmission when most men accurately know their HIV status, but additional modeling is needed to address the effectiveness of broader seroadaptive behaviors. The types of information withwhichMSMmake seroadaptive decisions is expanding to include viral load, treatment status, and HIV status based on home-use tests, and recent research has begun to examine the entire seroadaptive process, from an individual's intentions to seroadapt to their behaviors to their risk of acquiring or transmitting HIV and other STIs. More research is needed to craft clear public health messages about the risks and benefits of seroadaptive practices. PMID- 24234491 TI - A new tandem mass spectrometer for the study of molecular dissociations. AB - A new tandem mass spectrometer has been developed for the study of molecular fragmentation reactions. The first stage of this tandem mass spectrometer is a double-focusing sector field instrument in the BE configuration. The second stage is a double-focusing combination of a Wien filter and a sector magnet that allows simultaneous detection of a wide range of masses owing to the approximately equal velocities of the fragment ions. By using a microchannel plate as a collision target, high fragmentation effi.ciency and high ion transmission were achieved. PMID- 24234492 TI - Novel tandem quadrupole-acceleration-deceleration mass spectrometer for neutralization-reionization studies. AB - A new tandem mass spectrometer of the quadrupole-acceleration lens-deceleration. lens-quadrupole (QADQ) configuration is described. The instrument is designed for neutralization-reionization studies and consists of a 2000-u quadrupole mass analyzer as MS-I, an acceleration electrostatic lens, a series of three differentially pumped collision cells, and an electrostatic deceleration lens, energy filter, and another 2000-u quadrupole mass analyzer as MS-II. The ion optical system achieves high total ion transmission for 5-9-keV ions. Unit mass resolution in neutralization-reionization mass spectra of aromatic compounds is demonstrated. Mass, kinetic energy, and linked scans at various levels of mass resolution and sensitivity are described. PMID- 24234494 TI - Gas-phase ion-molecule reactions of the CH3O (+) cation. AB - The methoxy cation, CH30(+), formed by collision-induced charge reversal of methoxr anions with a kinetic energy of 8 keY, has been differentiated from the isomenric CH2OH(+) ion by performing low kinetic energy ion-molecule reactions In the radiofrequency-only quadrupole of a reverse-geometry double-focusing quadrupole hybrid mass spectrometer. The methoxy cation reacts with CH3SH, CH3 CH=CH2, (CH3)2O, and CH3CH2Cl by electron transfer, whereas the CH2OH(+) ion reacts by proton transfer with these substrates. PMID- 24234493 TI - Comparison of helium and argon as collision gases in the high energy collision induced decomposition of MH(+) ions of peptides. AB - Collision-induced decompositions (CID) of protonated peptides were studied using a four-sector mass spectrometer. The collision gases employed were helium and argon. The CID spectra of several peptides covering the molecular mass region of 905-2465 u were recorded. These investigations established several previously unrecognized differences between the CID spectra obtained with helium and argon as collision gases. These can be summarized as follows: (1) Structurally significant and specific side chain fragmentations (dn (f), wn (f) and vn, ion types) are greatly reduced or completely missing in the CID spectra obtained with helium as a collision gas compared to those obtained with argon. (2) As the peptide molecular mass increases, argon, which is heavier than helium, is increasingly more efficient than helium for generating fragment ions. PMID- 24234495 TI - Ion-molecule reactions and collision-activated dissociation of C4H 4 (+.) isomers: A case study in the use of the MS (3) capabilities of a pentaquadrupole mass spectrometer. AB - Isomeric C4H 4 (+.) radical cations vinylacetylene (a), butatriene (b), methylene cyclopropene (c), and the nonaromatic cyclobutadiene (d), generated, respectively, from the neutral precursors 3-butyn-1-ol (1), 1,4-dichloro-2-butyne (2), benzene (3), and 7,8-benzotricyclo [4.2.2.0(2,5)]deca-3,7,9-triene (4), undergo diagnostically different ion-molecule reactions with allene, isoprene, furan, and thiophene. It is speculated that adducts are generated by [2 + 2] cycloadditions with the first reagent and [4 + 2] Dials-Alder cycloadditions with isoprene, furan, and thiophene. The initially formed cycloaddition adducts fragment rapidly, isomerize, or undergo further addition of neutral reagent to yield a complex set of products. With a pentaquadrupole mass spectrometer, MS(3) experiments that employ three stages of ion mass analysis are used to help elucidate the ion-molecule reactions and to distinguish the isomeric C(4)H 4 (+.) ions. Among these experiments, the reaction intermediate spectrum reveals the nature of the intermediates connecting the reactant to a selected product while the sequential product spectrum provides mechanistic and structural information on the adducts and other ion-molecule products. The unique combination of ion molecule reactions with collision-activated dissociation employed here provides valuable information on the chemistry of ionized cyclobutadiene, including its proclivity to undergo [2 + 2] and [4 + 2] cyc1oadditions. PMID- 24234496 TI - Effects of functional group interactions on the bimolecular and dissociation reactions of diols. AB - The influence of functional group interactions on the bimolecular and dissociation reactions of diols were examined in a quadrupole ion trap mass spectrometer. Reactions of dimethyl ether ions with diols resulted in formation of (M + H)(+) ions and (M + 13)(+) ions (by net methyne addition). The product distribution depended on the relative separation of the hydroxyl groups within each diol, with the more proximate diols producing the greatest abundance of (M + 13)(+) ions compared to (M + H)(+) ions. The enhancement of the formation of (M + 13)(+) ions is attributed to the capability for electrostatic interactions between the hydroxyl groups and the electropositive methylene group of the methoxymethylene reagent ion. The enhancement is most significant for diols that can adopt five- or to a lesser extent six-membered ring transition states (i.e, any 1,2 or 1,3 diol). Collision-activated dissociation (CAD) techniques, including both sequential activation experiments (MS (n) ) and comparison of CAD spectra for model compounds, suggest that the (M + 13)(+) ions are protonated cyclic diethers. PMID- 24234497 TI - Determination of orders of relative alkali metal ion affinities of crown ethers and acyclic analogs by the kinetic method. AB - Ladders of relative alkali ion affinities of crown ethers and acyclic analogs were constructed by using the kinetic method. The adducts consisting of two different ethers bound by an alkali metal ion, (M1 + Cat + M2)(+), were formed by using fast atom bombardment ionization to desorb the crown ethers and alkali metal ions, then collisionally activated to induce dissociation to (M1 + Cat)(+) and (M2 + Cat)(+) ions. Based on the relative abundances of the cationized ethers formed, orders of relative alkali ion affinities were assigned. The crown ethers showed higher affinities for specific sizes of metal ions, and this was attributed in part to the optimal spatial fit concept. Size selectivities were more pronounced for the smaller alkali metal ions such as Li(+), Na(+), and K(+) than the larger ions such as Cs(+) and Rb(+). In general, the cyclic ethers exhibited greater alkali metal ion affinities than the corresponding acyclic analogs, although these effects were less dramatic as the size of the alkali metal ion increased. PMID- 24234498 TI - Reaction of analyte ions with neutral chemical ionization gas. AB - Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA Ion-molecule reactions of neutral methane with analyte ions under normal methane chemical ionization conditions are discussed. Reactant ions can be generated by direct electron ionization (EI) fragmentation, chemical ionization (CI) fragmentation, or collision-induced dissociation (CID). Examples in which products of such reactions appear in mass spectra in both conventional CI sources in "beam" instruments and low pressure CI in a quadrupole ion trap are presented. Also shown is an example in which MS/MS product ions react with neutral methane used for CI in an ion trap. It is shown that it is relatively straightforward to recognize such reactions in a quadrupole ion trap and in certain cases to minimize or preclude them. Effects of various operating parameters have been investigated and are discussed. PMID- 24234499 TI - Spectral deconvolution for overlapping GC/MS components. AB - The use of mass chromatogram peak centroids has been investigated as a means of deconvoluting the spectra of overlapping gas chromatography/mass spectrometry components. The peak centroids have been calculated with a precision of 0.04 scans (sd). This proved sufficient to allow deconvolution of the mass spectra belonging to two chemical components which were eluted 0.48 scans apart. For a more complex chromatography peak, it was possible to deconvolute the spectra of six components which were eluted within a 9 scan window. All the spectra produced by using this deconvolution mechanism agreed well with National Institute of Standards and Technology database spectra. PMID- 24234500 TI - Application of nanoscale packed capillary liquid chromatography (75 MUm id) and capillary zone electrophoresis/electrospray ionization mass spectrometry to the analysis of macrolide antibiotics. AB - Nanoscale separation techniques, nanoscale packed capillary columns (75 MUm id), and capillary zone electrophoresis (CZE), on-line with electrospray mass spectrometry (ESI/MS), were applied to the separation of a series of ten macrolide antibiotics. Both techniques use sub-microliter-per-minute flow rates through the analytical column and therefore require an electrospray probe that incorporates coaxial sheath flow. Positive ion electrospray mass spectra of these compounds yielded mainly protonated molecules. Fragmentation to yield structurally significant fragment ions was achieved by collision-induced dissociation (CID) at increased skimmer voltages. Separations were achieved using both techniques, with CZE/ESI/MS showing improved peak shapes and detection limits combined with faster analysis times. Nanoscale packed capillary columns provided better chromatographic resolution and was less susceptible to peak broadening caused by overloading of the analytes. PMID- 24234501 TI - The application of normal phase liquid chromatography/mass spectrometry by using coaxial continuous flow fast atom bombardment. AB - This article describes the interfacing of a normal phase fused silica capillary high performance liquid chromatography system to a magnetic sector mass spectrometer by using continuous flow fast atom bombardment (CFFAB). While the performance of CFFAB using reversed phase techniques is well understood, there is very little if any documentation on interfacing nonaqueous normal phase systems with CFFAB. This article describes the use of packed fused silica capillary liquid chromatography columns and the corresponding normal phase solvent systems. The experimental parameters required with nonaqueous solvent systems differ significantly from those of aqueous solvent systems. Ditallowdimethylammonium chloride (DTDMAC), a cationic surfactant commonly used as the active ingredient in fabric softener products, was chosen as a model compound to demonstrate the technique. DTDMAC was identified in a commercially available fabric softener product by using on-line normal phase liquid chromatography/mass spectrometry with accurate mass and tandem mass spectrometry. PMID- 24234502 TI - Analysis of an egyptian mummy resin by mass spectrometry. AB - Fast atom bombardment combined with mass spectrometry (FAB/MS), high resolution FAB/MS, FAB tandem mass spectrometry (MS/MS), and gas chromatography/mass spectrometry (GC/MS) were used to determine the composition of the resinous material recovered from the wrappings of an Egyptian mummy believed to be from the Roman period (100-350 A.D.). FAB/MS and MS/MS studies identified several oxidation products of abietic acid as the principal resin components, indicating that one or more species of coniferous trees were used by the Egyptians as a source of the resin. GC/MS studies also identified several n-alkanes with carbon numbers from C19 to C33 in the sample. The relative amounts of these n-alkanes, along with characteristic trace metals, indicate that bitumen, an asphalt native to the region, was added to the resin. The presence of this ancient source of carbon in this sample explains the inconsistent date assigned to the mummy by carbon-14 analysis. PMID- 24234503 TI - High pressure trapping in Fourier transform mass spectrometry: A radiofrequency only-mode event. AB - A new event for the Fourier transform mass spectrometry (FTMS) sequence is developed and demonstrated. During this event, called a radiofrequency (RF)-only mode event, the typical passive cubic trap of a Fourier transform mass spectrometer is made to operate as an active quadrupole ion trap. The transition between active and passive modes is developed so that ion loss as a consequence of the transition can be held to 15% or less. The adduct of the ion-molecule reaction of the 1,3-butadiene radical cation and methyl vinyl ether was detected during the Rf-only-mode event at a helium pressure of ~1*10(-3) torr even though this adduct is not detectable under standard FTMS operating conditions. PMID- 24234506 TI - Workplace surveillance for carpal tunnel syndrome using hand diagrams. AB - Four hundred and eleven workers from 4 different companies participated in a worksite screening program designed, in part, to estimate the prevalence of carpal tunnel syndrome (CTS). Each worker completed a discomfort survey and underwent limited nerve conduction testing of the median and ulnar sensory nerves in both wrists. The discomfort survey included a hand diagram which allowed subjects to shade in area(s) affected by numbness, burning, tingling, or pain. The discomfort survey also asked each worker to indicate whether she or he had experienced neuropathic symptoms (i.e., numbness, burning, tingling, or pain) in the wrist, hand or fingers of each hand, without regard to localization (i.e., median versus ulnar versus radial distribution), and also nocturnal occurrence of symptoms. Analyses involved comparing hand diagram scores and non localized wrist/hand/finger symptoms with electrodiagnostic test results. All configurations of hand diagram scores of the dominant hands had a statistically significant association with electrophysiologically determined median nerve dysfunction, but so did non localized symptom reports. The sensitivity, specificity, and positive predicted values of hand diagrams were poorer than those reported previously. While some test performance characteristics of hand diagrams were better than those for non localized distal extremity symptoms consistent with CTS, some were worse. Overall, our data suggest that hand diagrams are no better than using a questionnaire to determine if workers have experienced symptoms consistent with CTS in their wrists, hands or fingers without regard to localization. The choice of screening tool would depend on the goal of screening, in particular, whether it is more desirable to have slightly higher sensitivity or positive predictive value. PMID- 24234507 TI - Prevalence of psychopathology in carpal tunnel syndrome patients. AB - This study assessed the prevalence rates of psychopathology in acute carpal tunnel syndrome (CTS) and acute low back pain (LBP) patients. Psychopathology was assessed with the Structured Clinical Interview for the DSM-III-R (SCID). The results showed that the CTS patients had significantly higher rates of anxiety disorders, both current and lifetime, than the LBP patients. However, LBP patients had significantly higher rates of lifetime substance abuse than the CTS patients. In regard to other types of psychopathology, such as depression, current substance abuse, and somatoform pain disorders, CTS patients had similar rates as the LBP patients. It was concluded that anxiety disorders may be a concomitant of carpal tunnel syndrome, and that treating psychological problems along with physical aspects of the syndrome may increase the patient's chance of a successful therapeutic outcome. PMID- 24234505 TI - alpha-Ketoglutaramate: an overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle. AB - Glutamine metabolism is generally regarded as proceeding via glutaminase catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to alpha-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to alpha-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to omega-amidase. Transamination of glutamine results in formation of the corresponding alpha-keto acid, namely, alpha-ketoglutaramate (KGM). KGM is hydrolyzed by omega-amidase to alpha-ketoglutarate and ammonia. The net glutaminase II reaction is: L - Glutamine + alpha - keto acid + H2O -> alpha - ketoglutarate + L - amino acid + ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance. PMID- 24234508 TI - Early return to work following an aggressive rehabilitation program initiated one day after spine surgery. AB - In a program designed and conducted in a private rehabilitation center, 38 postoperative cervical or lumbar spine patients were treated with an aggressive rehabilitation regimen. The regimen included an aquatic component, stabilization and flexibility exercises, resistance and aerobic exercises, progressively difficult walks, educational sessions, and limited palliative modalities. Readiness for discharge was evaluated on the basis of clinical observations and submaximal cardiovascular testing, and a computer analysis comparing range of motion, strength, and functional capacity with normative data. No complications developed during the recovery of any patients. After an average of 3.3 days following discharge from the rehab program, 89% returned to their former occupations without restrictions. At follow-up, all patients had been working continuously at their occupation for over 25 months post-discharge. The authors conclude that, based on this retrospective analysis, this is a safe means of potentially reducing hospital time, minimizing postoperative morbidity, and restoring patients to their former occupations. These findings can only be viewed as preliminary, however, and further study in a prospective, controlled clinical trial is needed to draw definitive conclusions regarding the effectiveness of this aggressiveness rehabilitation program in the general population of postoperative spine patients. PMID- 24234509 TI - Chronic back pain and work disability: Vocational outcomes following multidisciplinary rehabilitation. AB - Studies indicate that work disabled chronic back pain patients out of work for longer than three months have a reduced probability of returning to work. The escalating personal and economic costs (indemnity and health care) associated with such long term disability have facilitated efforts at multiple levels to prevent and more effectively manage work disability. Multidisciplinary rehabilitation (MDR) targeted at return to work represents one such approach. The approach is based upon a multidimensional conceptualization of work disability and integrates medical, physical, psychological, educational and vocational interventions to increase physical function, reduce pain, increase stress coping skills and facilitate return to work. Seven outpatient multidisciplinary rehabilitation outcome studies for chronic back pain were identified that met the following selection criteria: 1) diagnosis of back pain, low back pain, spinal disorder (specific and nonspecific diagnosis), 2) chronic back pain of either longer than three months since injury or longer than three months absence from work, 3) use of an outpatient multidisciplinary rehabilitation approach that included some combination of medical management, physical conditioning, pain and stress management, vocational counseling/placement and education regarding back safety and health, and 4) work reentry was the primary focus of outcome. These were reviewed to determine the effectiveness of MDR in terms of return to work outcome. Analyses revealed that an average of 71 percent of work disabled chronic back pain patients who completed a multidisciplinary rehabilitation program were working or involved in vocational rehabilitation efforts at 12 month follow-up in contrast to an average of 44 percent in corresponding comparison groups. While these studies suggest the clinical utility of a multidisciplinary approach as compared to usual care in facilitating return to work for chronic back pain patients, the literature was characterized by several methodological limitations including the absence of randomization in the majority of studies, use of insurance company denials as control groups, heterogenous samples in terms of duration of work disability, job availability at discharge, extent of impairment and disability, age and duration of pain disorder, lack of specification as to exact treatment delivered in the control or usual care groups and varying definitions of return to work outcome. Research on predictors of return to work outcome following MDR were identified and included variables in five categories: demographics, medical history, physical findings, pain and psychological characteristics. The literature provides support for the use of integrated approaches that target the medical, physical, ergonomic and psychosocial factors that can exacerbate and/or maintain work disability. Future research should address current methodological limitations in the literature and focus on: 1) identifying critical treatment components of such approaches, 2) developing innovative screening methods to identify high risk cases to facilitate earlier more targeted efforts to assist such individuals, and 3) consider variations in the staging of various combinations of interventions in an effort to develop more cost-effective variations in the multidisciplinary approach. PMID- 24234510 TI - Issues and concerns in accommodating the elderly in the workplace. AB - Aging is a natural phenomenon affecting mankind. The more recent interest in the elderly is probably derived from the facts that: (1) currently more and more people are living into old age as compared to populations prior to early twentieth century, (2) people now recognize and appreciate the concept of retirement (until comparatively recently only a small proportion of the population lived into old age), and (3) economic necessities are pushing retirees back into the workforce. With people living and working longer, employers, social scientists, and medical and health professionals are having to gear themselves to solve a special category of problems-problems dealing with accommodating the elderly in the workplace, homes, recreational facilities, vehicles, etc. The purpose of this paper is to highlight some of the important issues that must be addressed when bringing, or retaining, the elderly in workplaces. The paper is divided into four main sections. The first section is devoted to defining the elderly. In the second section, discussion is focused on how and why the elderly have become an increasingly important part of the working environment. The biological effects of aging are discussed in the third section. In the last section, attention is paid to those age-related functional abilities that are essential consideration in accommodating the elderly in the workplaces. PMID- 24234511 TI - Knockdown of Pex11beta reveals its pivotal role in regulating peroxisomal genes, numbers, and ROS levels in Xenopus laevis A6 cells. AB - Peroxisomes are organelles that are ubiquitously found in all eukaryotic cells. Enzymes within their lumen are responsible for a variety of processes including the metabolism of fatty acids and eradication (neutralization) of free radicals. Peroxisomes are dynamic organelles, able to alter their numbers in response to a variety of different metabolic and cell-specific cues. Changes in peroxisome numbers can occur through division of preexisting peroxisomes or through de novo biogenesis from the ER. Proteins such as the Pex11 family of peroxins have been implicated as regulatory factors involved in peroxisome division. Division of peroxisomes involves elongation and membrane constriction followed by fission, which requires Pex11beta. The regulation of peroxisome numbers in different cell types and tissues is variable and poorly understood. Here, we examine how knockdown of Pex11beta affects peroxisomal genes, proteins, and peroxisome numbers in A6 kidney epithelial cells derived from Xenopus laevis. Pex11beta morpholino use subsequently decreased mRNA levels of Pex1, PMP70, and PPARgamma. Moreover, the Pex11beta morpholino decreased PMP70 protein levels and PMP70 positive structures. Furthermore, the marker GFP-SKL revealed fewer peroxisome like structures. These decreases resulted in increased levels of H2O2 and cellular and mitochondrial reactive oxygen species as measured by Amplex Red, DCFDA, and MitoTracker assays, respectively. PMID- 24234512 TI - Bovine mammary epithelial cell cultures for the study of mammary gland functions. AB - In the present study, the analysis of epithelial cells derived from various sources was undertaken, beginning from the mammary gland tissue through the primary cultures and their subsequent passages. The objective of the study was the comparative analysis of the stage in which the epithelial cells obtained from individuals in different lactation cycles and disparate phases of cell culture growth are the most suitable for morphological research and analysis of gene expression activity. The cultures of primary bovine mammary epithelial cells and passages were identified morphologically using immunocytochemical methods. After positive identification, real-time PCRs were performed for the analysis of the expression level of casein genes, whey protein genes, and butyrophilin gene. The most stable reference genes in real-time PCRs for the mammary gland tissue and cell cultures were also determined. Of the reference genes, the UXT and GAPDH genes appeared to be the most stable ones for the mammary gland tissue samples and epithelial cell cultures. The results obtained allowed concluding that the mammary gland samples collected from heifers constituted the most effective material for the initiation of primary cultures. The primary cultures formed characteristic for the mammary gland tissue dome structures, which images were obtained using confocal microscopy. The highest levels of expression of the CSN1S1, CSN1S2, CSN2, and CSN3 genes were detected in primary cultures. The levels of expression of whey protein genes (LALBA and BGL) were highest in the second passage. The most abundant expression of the BTN1A1 gene was observed in primary cultures and the third passage. On the basis of the whole experiment, it can be concluded that primary cultures and cells of the second passage derived from heifer individuals appeared to be the best materials for the analysis of mammary gland function and gene expression activity. PMID- 24234513 TI - Novel oral anticoagulants for stroke prevention in the geriatric population. AB - Prior to the availability of several newer anticoagulant medications, there had been no new advances in anticoagulation management for stroke prevention since the advent of warfarin in the 1950s. The availability of the novel oral anticoagulants (NOACs) dabigatran, rivaroxaban,and apixaban represent improvements over warfarin in many respects, including the elimination of the need for therapeutic drug monitoring, fewer drug and food interactions,and favorable efficacy; however, these agents are not without risk. Specifically, the use of the NOACs in the geriatric population, who are more likely to have an increased risk of stroke due to atrial fibrillation and other medical comorbidities, is not without risk. The objective of this review is to update the clinician on the use of the NOACs in the geriatric population and introduce the controversies and risks surrounding these newer therapies. PMID- 24234514 TI - The content of fluoride, calcium and magnesium in the hair of young men of the Bantu language group from Tanzania versus social conditioning. AB - The present study aimed at analysing the content of fluorine (F), calcium (Ca) and magnesium (Mg) in the hair of young male students (n =52) of a secondary school in Mafinga in Tanzania (Africa) who participated in anthropological examinations. Ca and Mg concentrations were determined using atomic absorption spectrophotometer while F levels using a potentiometric method. F in the hair of boys from older group (>=16 years old; n =24) was significantly higher than in the younger group (<16 years old; n =28) versus Ca and Mg levels. High carbohydrate diet was predominant- mainly based on corn or bean and meat served once a week, with few fruit and raw vegetables. Collective catering in the dormitory reflected habits and culinary preferences at home. The lack of balanced diet, with majority of the nutritional energy supplied by easily accessible and cheap carbohydrates, was reflected in dietary deficiencies, characterised, among others, by visible skin conditions and tooth decay. PMID- 24234515 TI - Peripheral ulcerative keratitis as the presenting feature of systemic rheumatoid vasculitis without joint involvement. PMID- 24234516 TI - p53 antibody: is it an indicator of dedifferentiated thyroid cancer? AB - AIM: Radioiodine is the most effective treatment modality in differentiated thyroid carcinoma, either in metastatic or residual thyroid tissue. However, sometimes dedifferentiation can develop and the effectiveness of radioactive I 131 decreases. The p53 is a tumor suppressor gene which plays an important role in controlling normal cell proliferation regulation. In the serum of healthy individuals, the presence of p53 autoantibodies is extremely rare. Mutations in this gene cause an accumulation of non-functional proteins and may lead to development of anti-p53 antibodies. The aim of the present study was to devise a simple blood test that could lead to early identification of patients with dedifferentiation. In this respect, we investigate whether the serum level of anti-p53 antibody is of diagnostic value in the follow-up of patients with high levels of thyroglobulin (Tg) and negative I-131 scan. MATERIALS AND METHODS: Patients who were diagnosed with thyroid cancer, treated with total or near total thyroidectomy and referred for I-131 therapy or low dose I-131 whole body scan were included in our study. Blood samples were taken before the administration of I-131 orally in the group of patients. Besides, 28 healthy subjects were included. We quantified the presence of p53 autoantibodies from serums. RESULTS: In the present study were enrolled 171 patients with a mean age of 47.7+/-13.5 years (range 16-80 years) and 28 healthy subjects with an age range of 18-52 years (mean 36.0+/-9.8 years). One hundred and forty-eight patients had papillary (86.5%), 7 (4.1%) follicular, 10 (5.8%) thyroid tumors of uncertain malignant potential, 2 (1.2%) Hurthle cell carcinoma, 3 (1.8%) poor differentiated, and 1 (0.6%) undifferentiated thyroid carcinoma. The p53 antibodies were positive in 16 (9.4%) patients and negative in 155 (90.6%). The p53 antibodies were positive in 3 (10.7%) healthy subjects, and negative in 25 (89.3%) healthy subjects. In five patients with high Tg level and negative radioiodine scan, who were accepted as dedifferentiated, p53 antibodies were also negative. CONCLUSION: The results of the present study suggested that the level of serum p53 antibody seems to be of limited value in the demonstration of dedifferentiation in thyroid cancer patients. PMID- 24234517 TI - Codling moth,Cydia pomonella, (Lepidoptera: Tortricidae): Is its sex pheromone multicomponent? AB - When the nine identified components in the effluvium of calling female codling moths were compared to pure synthetic (E,E)-8,10-dodecadien-1-ol in flight-tunnel tests, equal responses were obtained over a concentration range of 300-fold. When synthetic (E,E)-8,10-dodecadien-1-ol was compared to extract of female sex pheromone glands by a male wing-flutter bioassay, or in flight-tunnel tests, equal responses were obtained over a concentration range of 1000-fold. The sum total of these and previous studies indicate that the codling moth sex pheromone consists of only one component. PMID- 24234518 TI - Bioassay approaches to assessing behavioral responses of plum curculio adults (Coleoptera: Curculionidae) to host fruit odor. AB - We evaluated several approaches to developing a simple, sensitive, and reliable laboratory bioassay of responses of overwintered adult plum curculios (PCs),Conotrachelus nenuphar (Herbst), to host fruit odor or its attractive components. A high proportion of assayed PCs responded positively to odor of wild plums under no-choice, moving-air conditions in a wind tunnel and under dual choice, still-air conditions in enclosed Petri dishes. Positive response to controls lacking host odor, however, was much greater in the wind tunnel, arguing in favor of bioassays under dual-choice conditions in still air to provide greater PC discrimination. Response to host odor (from wild plums or hexane extract of wild plums or Liberty apples) in Petri dish bioassay chambers proved greatest: (1) during the scotophase of PCs under total dark or dim red light conditions, (2) when Petri dishes were completely enclosed, (3) when PCs were starved for 24 or 48 hr, and (4) when PCs were tested within seven weeks after apple tree petal fall. Neither the sex of a PC nor the direction in which a PC was obliged to move to find the source of host odor (upward through a port in the Petri dish lid or downward through a port in the base) had a substantial effect on level of response to host odor or discrimination of host odor from a nonodorous control. We conclude that an enclosed Petri dish bioassay chamber of the type described here should be a valuable asset in the process of chemically identifying components of host fruit odor attractive to PCs. PMID- 24234519 TI - Allelopathic potential ofIpomoea tricolor (Convolvulaceae) in a greenhouse experiment. AB - The allelopathic potential ofIpomoea tricolor, a plant used in Mexican agriculture to control weeds, and tricolorin A, the major phytogrowth inhibitor present in the so-called "resin glycosides" of this plant, have been evaluated by testing leachates of the plant and the compound on the germination and radicle growth ofAmaranthus hypochondriacus, Echinochloa crusgalli, Senna uniflora, I. tricolor, andI. purpurea. The allelopathic potential ofI. tricolor was evaluated in a greenhouse experiment with dryI. tricolor mixed with sterile and nonsterile soil in pots.A. hypochondriacus was sown in pots containingI. tricolor, 2-chloro 4-(ethylamino)-6-(isopropylamino)-1,3,5 triazine (Gesaprim) or 1-glyphosphate, and the glyphosphate salt of isopropylamine (Faena), two different commercial herbicides used as a comparison toI. tricolor. Number and dry weights of different monocotyledonous and dicotyledonous weeds andA. hypochondriacus growing in the different treatments were measured.Ipomoea and Faena herbicide had a similar inhibitory effect on monocots. PMID- 24234520 TI - Variation in condensed tannin concentration of a temperate grass (Holcus lanatus) in relation to season and reproductive development. AB - Holcus lanatus, a temperate grass, was found to contain low but measurable concentrations of condensed tannins (CT), according to the vanillin-HCl and the butanol-HCl methods. The variation in CT concentrations between different types of tissue including leaf age and reproductive versus nonreproductive tissue was examined. There was no evidence that floral tissue contained more CT than nonreproductive tissue. A sequential extraction and analysis procedure showed a decreasing proportion of free-unbound CT and greater preponderance of protein bound and fiber-bound CT with increasing leaf age and in dead matter. Samples collected from an agricultural pasture on two sampling dates, January 24 and March 5, 1993, showed short-term temporal variation in free-unbound CT. PMID- 24234521 TI - Comparison of antialgal activity of brown-rotted and white-rotted wood andIn situ analysis of lignin. AB - Brown-rotted wood has been used as a source of lignin to investigate further the antialgal effects of lignocellulosic materials such as decomposing barley straw. The antialgal activity of brown-rotted and white-rotted wood has been determined in a laboratory bioassay. Using pyrolysis gas chromatography-mass spectrometry, the lignin of the rotted wood samples has been compared and the significance of the structure of the lignin in antialgal activity is discussed. PMID- 24234522 TI - Mechanism underlying cuticular hydrocarbon homogeneity in the antCamponotus vagus (SCOP.) (Hymenoptera: Formicidae): Role of postpharyngeal glands. AB - The aim of the present study was to investigate the regulation and the homogeneity of the chemical signature between members ofCamponotus vagus after experimentally changing the cuticular chemical signature by topically applying hydrocarbons. Topical application of pentane (solvent) to the cuticle of isolated workers led to a significant decrease in the quantities of the cuticular hydrocarbons measured within 3 hr, followed by an increase within the following 3 hr and a period of relative stability from 9 hr to 14 days. On the other hand, after topical application to isolated workers ofn-tetracosane, a hydrocarbon existing only in trace quantity in this species, the quantity of this hydrocarbon measured over time in the epicuticular wax tended to level out at about 14 days after treatment. In contrast, topically applied (Z)-9-tricosene, an unsaturated hydrocarbon not normally synthesized by this species, decreased dramatically within a few hours and had completely disappeared within 14 days. (Z)-9-Tricosene applied to one member of a group was present in the postpharyngeal glands of the other members from 30 min to seven days of cohabitation. The highest levels were recorded in all six workers in each group after one day. GC-MS analyses showed that (Z)-9-tricosene was present in the cuticles of some untreated workers only after four and seven days of cohabitation with a treated worker. These data suggest: (1) that the deposited (Z)-9-tricosene decreased very quickly on the cuticle of the treated worker, although the total amount was spread over the cuticle and postpharyngeal gland and (2) that it was absorbed by the nontreated workers via the postpharyngeal glands during licking or grooming activities and reincorporated into the cuticle at four and seven days. When the treated worker was separated from the other ants by a wire mesh, (Z)-9-tricosene was detected neither in the cuticle nor in the postpharyngeal gland of nontreated workers. PMID- 24234523 TI - Indole as an olfactory synergist for volatile kairomones for diabroticite beetles. AB - Olfactory synergism, where combinations of plant volatile kairomones are quantitatively more attractive to insects than the sum of attraction of the individual components, is an important but little-studied phenomenon in host plant selection and feeding and in pollination ecology. Diabroticite beetles (Coleoptera: Chrysomelidae) are strongly attracted toCucurbita blossoms, and 2- to 3-fold olfactory synergism has been demonstrated in four species by combinations of the key blossom volatiles, 1,2,4-trimethoxybenzene, indole, and (E)-cinnamaldehyde. This TIC mixture represents an optimizedCurcurbita blossom volatile kairomone mixture useful in monitoring Diabroticite populations and in studying their behavior and ecology. Indole, which exhibits a spectrum of attraction to these beetles ranging from moderate forDiabrotica virgifera virgifera andAcalymma vittatum to very weak forD. barberi, is the primary synergistic component. Indole combined with 4-methoxycinnamaldehyde was significantly synergistic toD. v. virgifera at a ratio of 1:300 and produced 4 fold synergism at a ratio of 1:1. Indole combined with 4-methoxyphenethanol was less synergistic toD. barberi with 1.5- to 2-fold synergism at a 1:1 ratio. These consistent variations in diabroticite beetle olfactory responses presumably indicate evolutionary divergences in the numbers of relict indole antennal receptors. PMID- 24234524 TI - Distribution of autogenous and host-derived chemical defenses inOreina leaf beetles (Coleoptera: Chrysomelidae). AB - The pronotal and elytral defensive secretions of 10Oreina species were analyzed. Species feeding on Apiaceae, i.e.,O. frigida andO. viridis, or on Cardueae (Asteraceae), i.e.,O. bidentata, O. coerulea, andO. virgulata, produce species specific complex mixtures of autogenous cardenolides.O. melanocephala, which feeds onDoronicum clusii (Senecioneae, Asteraceae), devoid of pyrrolizidine alkaloids (PAs) in its leaves, secretes, at best, traces of cardenolides. Sequestration of host-plant PAs was observed in all the other species when feeding on Senecioneae containing these alkaloids in their leaves.O. cacaliae is the only species that secretes host-derived PA N-oxides and no autogenous cardenolides. Differences were observed in the secretions of specimens collected in various localities, because of local differences in the vegetation. The other species, such asO. elongata, O. intricata, andO. speciosissima, have a mixed defensive strategy and are able both to synthesize de novo cardenolides and to sequester plant PA N-oxides. This allows a great flexibility in defense, especially inO. elongata andO. speciosissima, which feed on both PA and non-PA plants. Populations of these species were found exclusively producing cardenolides, or exclusively sequestering PA N-oxides, or still doing both, depending on the local availability of food-plants. Differences were observed between species in their ability to sequester different plant PA N-oxides and to transform them. Therefore sympatric species demonstrate differences in the composition of their host-derived secretions, also resulting from differences in host-plant preference. Finally, within-population individual differences were observed because of local plant heterogeneity in PAs. To some extent these intrapopulation variations in chemical defense are tempered by mixing diet and by the long-term storage of PA N-oxides in the insect body that are used to refill the defensive glands. PMID- 24234525 TI - Identification of female sex pheromone components of rice looper,Plusia festucae (L.), (Lepidoptera: Noctuidae). AB - The rice looper,Plusia festucae, is a defoliator of the rice plant. Chromatographic behavior, chemical reactions, and GC-MS analyses of the female sex pheromone revealed that the main component was (Z)-5-dodecenyl acetate (Z5 12: OAc, component I). The GC-MS analysis also indicated that the pheromone gland extract included another three monounsaturated components, (Z)-5-dodecen-l-ol (Z5 12: OH, component II), (Z)-7-tetradecenyl acetate (Z7-14: OAc, component III), and (Z)-7-tetradecen-l-ol (Z7-14: OH, component IV) in the following ratio: I:II:III:IV=100:6:15:1. In a paddy field, the mixture of synthetic I, II, and III in a ratio of 100:6:15 showed stronger attractancy than the virgin female, while the role of IV was unknown. PMID- 24234526 TI - Mammalian exocrine secretions: IX. Constituents of preorbital secretion of oribi,Ourebia, ourebi. AB - Using gas chromatography-mass spectrometry in conjunction with ancillary techniques such as chemical ionization with different reactant gases, determination of the position of double bonds by means of dimethyl disulfide derivatization, and finally gas chromatographic and mass spectrometric comparison with authentic synthetic material, 75 constituents were identified in the preorbital secretion of the male oribi,Ourebia ourebi. The secretion contains compounds with long-chain, unbranched structures similar to those found in many other preorbital secretions but with a finite volatility range, in contrast to the seemingly endlessly increasing chain lengths typical of other preorbital secretions. PMID- 24234527 TI - Volatiles emitted by different cotton varieties damaged by feeding beet armyworm larvae. AB - Volatile compounds elicited by insect herbivore feeding damage in five cotton cultivars and one naturalized cotton variety were examined by allowing beet armyworm larvae to feed overnight on leaves and collecting volatiles from the plants in situ. Of 23 compounds identified from larval damaged leaves, terpenes and lipoxygenase-hydroperoxide lyase-derived volatiles predominated. No pronounced differences in the levels of volatile emission were noted from leaves of undamaged plants of the different varieties. However, average volatile emission from damaged leaves of the naturalized variety was almost sevenfold higher than from damaged leaves of the commercial cultivars. This was despite the fact that larvae preferred feeding on the leaves of commercial cultivars over those of the naturalized variety in choice tests. PMID- 24234528 TI - Dioxins-furans-and no end. PMID- 24234530 TI - SETAC-Europe ABC Laboratories Environmental Education Award. PMID- 24234529 TI - The evaluation of pesticides and their primary toxic degradation products in drinking water from the viewpoint of human toxicology: Is it adequate? PMID- 24234531 TI - Altered human monocyte/macrophage function after exposure to diesel exhaust particles. AB - The relationship between immune defense mechanisms and environmental pollutants has been a focus of intensive research during the last decade. In animal experiments, diesel exhaust particles (DEP) have been shown to exert adjuvant effects on the IgE response against aeroantigens and to compromise broncho pulmonary immune defense. Important target cells are monocytes/alveolar macrophages which display the important functions of phagocytosis, antigenpresentation and modulation of inflammatory processes. To further evaluate the influence of DEP upon these cells, we investigated whether exposure to suspended DEP would change the phagocytic capacity and the tumor necrosis factor alpha (TNF-alpha) release of human peripheral monocytes/alveolar macrophages. Our results demonstrated a dose-dependent reduction of phagocytosis (p < 0.001) and an additional increase of an ongoing TNF-alpha response (p < 0.005). These findings may help to link exposure to environmental pollutants to such biologic effects as increased susceptibility to broncho-pulmonary disease or facilitated sensitization against aeroallergens. PMID- 24234532 TI - Individual PCBs as predictors for concentrations of non and mono-ortho PCBs in human milk. AB - 32 Dutch human milk samples were analyzed for PCBs with either HRGC-ECD or HRGC LRMS in the NCI mode. Samples were collected from three different locations in The Netherlands: Amsterdam, Rotterdam and Groningen. Quantitatively, no differences could be observed between the three localities, while in addition the congener specific pattern showed a striking similarity for all individual samples. Only principal component analysis revealed slight individual differences. Based on similarities in the PCB profiles, linear relationships were calculated between 2,3'4,4',5-PnCB (#118) or 2,2'4,4'5,5'HxCB (#153) and the most relevantnon andmonoortho PCBs exhibiting dioxinlike activity. These PCBs included 2,3,3',4,4'-PnCB (#105), 3,3',4,4'5-PnCB (#126) 2,3,3',4,4',5-HxCB (#156), 2,3,3',4,4',5'-HxCB (#157), 2,3',4,4',5,5'-HxCB (#167) and 3,3',4,4',5'5-HxCB (#169).Good linear relationships were observed between individual PCBs. Based on the results of this study, PCB #118 can be used to predict concentrations of the PCBs #105 and #126. PCB #153 can be used as a predictor for the PCBs #156, #157, #167 and #169, but also for the total toxic equivalencies (TEQs) ofnon andmonoortho PCBs present in human milk. This method using certain PCBs as predictors for other toxicological relevant congeners, can be useful and cost effective, e.g. for epidemiological studies. However, before applied a number of conditions should be met. These are: 1) A stable composition of the PCB matrix should be established. 2) A possible time dependent change in composition of the matrix should first be excluded when used over different time periods. PMID- 24234533 TI - Monitoring polycyclic aromatic hydrocarbons (PAHs) and heavy metals in urban soil, compost and vegetation. AB - Samples of urban surface soil, composts, leaves from avenue limetrees and grass from park areas of the city of Basel (Switzerland) were analysed for polycyclic aromatic hydrocarbons (PAHs) and heavy metals. Generally, significant lower levels of PAHs (10 times lower) and heavy metals (3-70 times lower) were found in vegetation samples than in composts or soils. The concentrations of PAHs in soil and compost samples were in the same order of magnitude although 10-100-times higher in comparison to data given for rural soils in other studies, whereas heavy metal contents in urban soils and composts were 2-3 times higher than in rural samples. Using multivariate statistical analysis, it was possible to define similarities or special characteristics of single substances or substance groups in a given matrix reflecting their chemical properties and providing information on their specific emission sources. PMID- 24234534 TI - Substance flows through the economy and environment of a region : Part I: Systems definition; Part II: Modelling. AB - In the tradition of the study of materials flows through society, the Substance Flow Analysis (SFA) method and its software tool SFINX are presented. SFA aims at providing the relevant information for a country's overall management strategy regarding single substances or coherent groups of substances. Three modelling techniques and their possibilities and limitations are discussed: Bookkeeping, static modelling, and dynamic modelling. The computer program SFINX can be used for varoius purposes: (1) to obtain an overview of stocks and flows of a substance in, out and through a nation's economy and environment for a specific year, (2) to trace the origins of specific pollution problems, and (3) to estimate the effectiveness of certain abatement measures. Each application has its own requirements with regard to data and modelling. PMID- 24234535 TI - Substance flows through the economy and environment of a region : Part I: Systems definition. AB - In the tradition of the study of materials flows through society, the Substance Flow Analysis (SFA) method is presented. SFA aims at providing the relevant information for a country's overall management strategy regarding single substances or coherent groups of substances. This article is dedicated to the presentation of a threestep general framework for SFA-type studies, and elaborates on its first step the systems definition. Attention is given to the definition of the external and internal system boundaries, the categorization of the system's elements, aspects of materials choice, time, and space, and how these depend on the aim of the conducted study. Moreover, a broader discussion is started on the need for standardization of materials flow studies in general. PMID- 24234536 TI - Index to measure environmental performance. PMID- 24234537 TI - Preface. PMID- 24234539 TI - The pesticide index. PMID- 24234538 TI - Uptake of terbuthylazine and its medium polar metabolites into maize plants. AB - The uptake of terbuthylazine and its medium polar metabolites into maize plants under outdoor conditions is investigated. For this purpose, a dynamical fate model consisting of soil, plant and air is developed. The model calculations are compared with experimental results of outdoor lysimeter tests, carried out with(14)C-labelled herbicide applied to sandy agricultural soil at a single application rate of 890 g/ha. Approximately 0.3 % of the applied activity remains in all the plants after the vegetation period. The model predicts that about three times that amount is volatilized from the plants into the air. Activity uptaken from soil and volatilized from plant surface into air is predominately associated with metabolites. During the whole vegetation period the fraction of unchanged terbuthylazine in the plants is very small (less than 1 % of the extractable activity). PMID- 24234540 TI - The biomethanation technology guide : A guide to successful industrial implementation of biomethanation technologies in the European union. PMID- 24234541 TI - Iron degrades chlorinated hydrocabons. PMID- 24234542 TI - EU-project CRAFT : Automatic reuse of electronic components on printed circuit boards and discharging of toxic components. PMID- 24234543 TI - Lagrangian dispersion model and its application to monitor nuclear power plants. AB - The Lagrangian dispersion model and its advantages while applying it in monitoring nuclear power plants in complex terrain at varying meteorological conditions is explained.The software developed has been installed at the Bavarian State Authority to monitor its six nuclear power plants.Input data are routinely measured meteorological data as well as emission data for iodine, aerosols and noble gas. PMID- 24234544 TI - The ACS division of analytical chemistry establishes home page on world wide web. PMID- 24234545 TI - A study on the potential sources of air pollutants observed at Tjorn, Sweden. AB - The Potential Source Contribution Function (PSCF) receptor model combines both chemical and meteorological information. In this study, PSCF was employed to identify the potential source emission regions for aerosol compositions measured at Tjorn, Sweden (58.01 ?N, 11.36 ?E). PSCF was for the first time applied on a European scale. One hundred and fifty-two four-day air parcel backward trajectories were combined with concentrations of sixteen elements determined in 33 coarse and fine aerosol samples. The observations were made between February 17 and March 26, 1985. The modeling results of the heavy metals V, Pb, Zn, and As are presented and compared with available emission inventory data. A number of known industrialized regions in the former USSR and Europe are found of high potential to be the emission source areas. These areas are in good agreement with the known emission information. The PSCF maps of total sulfur, Non-Seasalt-Sulfur (N.S.S.) and chlorine are also presented. High potential regions in the Arctic area exist in the PSCF map for total sulfur wheres they do not occur in that for N.S.S. PMID- 24234547 TI - Dioxins and related compounds : Status and regulatory aspects in Germany. PMID- 24234546 TI - Risk assessment of existing chemicals : Technical guidance documents adopted by the EU. PMID- 24234548 TI - Organohalogen compounds : Conference volumes from "Dioxin '95" and backlist. PMID- 24234550 TI - A simplified pathway for total knee arthroplasty improves outcomes. AB - Care pathways for total knee arthroplasty (TKA) demonstrate improved quality and utilization outcomes. Standardizing these processes over large systems is difficult due to the variability of practice patterns and the complexity of multistep pathways. A simplified approach to this process focusing on early activity and avoidance of continuous urinary catheters was performed to overcome these perceived barriers for implementing a system-wide care pathway. Data were collected from a total of 6,154 consecutive patients during the time period of 1 year before and 1 year after implementation of a pathway focusing on two key drivers: early activity and continuous urinary catheter avoidance. Patients included were adults admitted for elective primary TKA. A composite score was calculated based on the successful completion of the two key drivers. Outcome measures were tracked before and after implementation. Following implementation of a simplified TKA care pathway, there was a significant increase in the composite score with increases attributable to both increased early activity (p < 0.0001) and continuous urinary catheter avoidance (p < 0.0001). This improvement in composite score was associated with a significant decrease in hospital length of stay (HLOS) (p < 0.0001), costs (p < 0.0001), complications (p < 0.0001), and 30-day readmissions (p < 0.0106). A fixed-effect model analysis demonstrated early activity was associated with improvements in HLOS (p < 0.0001), complications (p = 0.0240), and 30-day readmissions (p = 0.0046). Avoidance of a continuous urinary catheter was associated with improvements in HLOS (p = 0.0001), costs (p < 0.0001), complications (p = 0.0006), and 30-day readmissions (p = 0.0008). A simplified care pathway for TKA focusing on early activity and continuous urinary catheter avoidance is associated with improved complications, costs, HLOS, and 30-day readmissions. PMID- 24234551 TI - Navigated versus conventional total knee arthroplasty. AB - Computer-aided navigation in total knee arthroplasty (TKA) promises improved alignment, performance, and survivorship. Previous meta-analyses demonstrated that navigation yields better component alignment; however, they did not discuss other indicators of performance. This meta-analysis compares navigated (NAV) and conventional (CONV) TKAs and includes clinical outcomes and adverse events. Forty seven studies (22 randomized trials) of varying methodological quality involving 7,151 TKAs created the sample population. Statistical analyses included analysis of variance of weighted means and random effects modeling. As seen in previous meta-analyses, NAV is favored over CONV TKA. Analysis of surgical characteristics found that length of surgery and tourniquet times were lower for CONV, but not significant. Meta-analysis found that tourniquet times favored CONV but not a strong relationship for length of surgery. Analysis of individual adverse events did not reveal any significant differences. However, when examining adverse events in their totality, the NAV experienced significantly fewer complications. TKA performed with imageless navigation improves component alignment, provides for lower blood loss, improves clinical outcomes as measured by Knee Society and WOMAC scores, and has fewer total adverse events. Published data are insufficient to determine any correlations between component alignment and outcomes. PMID- 24234552 TI - Indications for surgical management of osteochondritis dissecans of the knee in the pediatric population: a systematic review. AB - Several case series have been published exploring the surgical management of osteochondritis dissecans (OCD) of the knee in pediatric patients. This systemic review was performed to identify the surgical indications for this condition. A search of the Embase and Ovid Medline databases was performed to identify clinical studies reporting outcomes of surgical management of OCD in the knee in this patient population. A quality assessment of the included articles was conducted independently by two reviewers using a quality assessment tool developed by Yang et al. A total of 25 articles met the eligibility criteria and were reviewed; 40% of studies did not clearly describe their surgical indications. The remainder of the studies had a failure of nonoperative management with or without the concomitant use of imaging as their indication for surgery, or used lesion stability itself as the indication for surgery. This review outlines several surgical indications presented in the literature for the treatment of OCD lesions of the knee in the pediatric population. The most common indication for surgery was a failure of a trial of nonoperative treatment with or without the concomitant use of serial imaging. Although the quality of the case series was high, inconsistencies in reporting radiographic and arthroscopic classification of the OCD lesion were common. PMID- 24234553 TI - Preface. PMID- 24234554 TI - A new serial in the life sciences. What does this mean? PMID- 24234555 TI - Metabolic effects of feeding a high protein/low carbohydrate diet as compared to a low protein/high carbohydrate diet to rainbow troutSalmo gairdneri. AB - Groups of trout were fed either a high protein/low carbohydrate (HP/LC) or a low protein/high carbohydrate (LP/HC) diet for 16 weeks. Fish fed the HP/LC diet had significantly higher levels of protein, ninhydrin positive material and tryptophan in plasma as well as lipid and protein in liver, but lower levels of glucose in plasma, glycogen in liver and a lower hepatosomatic index compared with fish fed the LP/HC diet. There were no differences concentrations of tryptophan or serotonin in the brain of fish fed the different diets. Fish fed the HP/LC diet had significantly lower activities of glycolytic enzymes but higher activities of gluconeogenic enzymes compared with the group fed the LP/HC diet. Those enzymes measured concerned with the TCA cycle or initiating amino acid catabolism were generally unaffected by diet although activities of threonine dehydrogenase, alanine aminotransferase and glutamate dehydrogenase were higher in those fish fed the HP/LC diet. The data suggest that rainbow trout show little adaptation in activities of amino acid catabolising enzymes to variations in dietary protein intake. PMID- 24234556 TI - Protein degradation and protease activity of chum salmon (Oncorhynchus keta) muscle during spawning migration. AB - Sarcoplasmic protein content decreased significantly and myosin heavy chain was degraded gradually during spawning migration of chum salmon (Oncorhynchus keta).Acid and neutral proteinase activities increased significantly during spawning migration. These proteinase activities were higher in females than in males. High levels of acid proteinase were not caused by the injury of lysosomal membranes. Considering the physiological states of chum salmon, neutral proteinase activity might be related to the degradation of muscle protein.As the changes in serum sex steroids were similar to those in the protease activities during spawning migration, it was considered that high levels of protease activity during spawning migration were closely related to the serum levels of androgens. PMID- 24234557 TI - The effect of dietary lipids on the trout erythrocyte membrane. AB - Rainbow trout were fed either a commercial diet or semi-purified diets containing 8% by weight of either cod liver oil, grape seed oil or hydrogenated coconut oil. Important changes in the fatty acid composition of erythrocyte membrane phospholipids were induced by these dietary fats. No changes were seen in the cholesterol/phospholipid ratio and in the cellular ATP level. Shape changes (crenation of cell margin and shrinkage) were only seen in trout fed hydrogenated coconut oil in connection with an accumulation of high amounts of (n-9) fatty acids including 20:3 (n-9) phospholipids. The compositional changes affect the stability of the erythrocyte membrane. An increased rate of osmotic hemolysis appeared to be associated with an increased unsaturated fatty acid content of the membranes. PMID- 24234559 TI - Controversies in counseling for mitochondrial conditions. AB - A healthy woman sought preconceptional genetic counseling regarding a family history of a mitochondrial myopathy in her brother and retinitis pigmentosa (RP) in her two maternal aunts. Several questions were raised: (1) What is the likelihood of a familial mitochondrial condition? (2) What molecular tests or prenatal screening can we offer? (3) How would these tests help assess the likelihood of a familial mitochondrial condition? A mitochondrial mutation previously identified in the brother consisted of a heteroplasmic 2.9 kb deletion. We detected this deletion in the peripheral blood of the brother by PCR amplification of the deletion breakpoint, but not in his mother, the consultand, nor in one of the two aunts affected with RP. Although the molecular analysis was encouraging to the consultand, a familial mitochondrial disorder could not be eliminated with certainty. The pros and cons of prenatal testing for mitochondrial disorders are discussed in general, and as specifically related to this family. PMID- 24234558 TI - Counseling and screening for cystic fibrosis in patients with congenital bilateral absence of the vas deferens: Patient perceptions. AB - Congenital bilateral absence of the vas deferens (CBAVD) occurs in approximately 1.3% of infertile males and is thought to be, in most cases, a primarily genital form of cystic fibrosis (CF). Fourteen males with CBAVD considering microsurgical sperm aspiration from the epididymis (MESA) and in vitro fertilization were seen for genetic counseling and screening for CF. To retrospectively evaluate these patients' perceptions of the counseling and screening information, we conducted structured telephone interviews to assess their recall of information about CF and its impact on their health concerns and reproductive plans. We found that, as the health implications of CF are abstract and not as important to patients as the diagnosis of CBAVD itself, patients tend to view their CF status primarily in terms of their reproductive potential. Retrospective analysis afforded us an opportunity to identify the psychosocial issues of most concern to this unique patient population. PMID- 24234560 TI - Family history in ovarian cancer referral population. AB - In order to determine the incidence of familial and hereditary ovarian cancer in a referral patient population, we conducted a retrospective study of 44 patients from a consecutive set of 62 patients treated for ovarian carcinoma at the Gynecologic Oncology Clinic at the Richland Memorial Hospital Center for Cancer Treatment and Research between January 1, 1993 and December 31, 1993. In our study of the referred patients, only two (4.55%) reported a history of at least one first-degree relative also being affected with ovarian cancer. However, 13 patients (29.55%) reported a family history consistent with one of the hereditary ovarian cancer syndromes. In addition to having a suggestive family history, these 13 families demonstrated several cardinal features of hereditary cancer syndromes including early onset, bilaterality, multiple primary tumors, and transmission. Race was the only significantly different demographic factor between the hereditary and sporadic ovarian cancer groups. All 13 patients who appeared to have a hereditary form of cancer were Caucasian. PMID- 24234561 TI - Changing the definition of "proband" in the new standardized nomenclature for pedigrees. PMID- 24234562 TI - Code of ethics: Day-to-day applications. PMID- 24234563 TI - A framework for daily activity monitoring and fall detection based on surface electromyography and accelerometer signals. AB - As an essential branch of context awareness, activity awareness, especially daily activity monitoring and fall detection, is important to healthcare for the elderly and patients with chronic diseases. In this paper, a framework for activity awareness using surface electromyography and accelerometer (ACC) signals is proposed. First, histogram negative entropy was employed to determine the start- and end-points of static and dynamic active segments. Then, the angle of each ACC axis was calculated to indicate body postures, which assisted with sorting dynamic activities into two categories: dynamic gait activities and dynamic transition ones, by judging whether the pre- and post-postures are both standing. Next, the dynamic gait activities were identified by the double-stream hidden Markov models. Besides, the dynamic transition activities were distinguished into normal transition activities and falls by resultant ACC amplitude. Finally, a continuous daily activity monitoring and fall detection scheme was performed with the recognition accuracy over 98%, demonstrating the excellent fall detection performance and the great feasibility of the proposed method in daily activities awareness. PMID- 24234564 TI - Principles of collisional activation in analytical mass spectrometry. AB - Collisional activation has played an essential role in the development of mass spectrometry/mass spectrometry (MS/MS). It was the first activation method to be employed and continues to be by far the most widely used. As instrumentation for MS/MS has evolved it has been found that collisional activation can be effected under a remarkably wide range of conditions for a wide range of ions. It is fair to conclude from the growth of MS/MS over the past fifteen years that collisional activation has been spectacularly successful. However, it has limitations. As a community, we have learned much over the years regarding these limitations both from empirical and fundamental points of view. This overview provides background on the development of collisional activation and discusses the importance of the interaction potential and timing on mechanisms for energy transfer. Parts of the discussion is devoted to changing reference frames from the laboratory to the center of mass to simplify visualizing what is possible and what is probable in collisional activation. PMID- 24234565 TI - Trapping and detection of ions generated in a high magnetic field electrospray ionization fourier transform ion cyclotron resonance mass spectrometer. AB - The trapping and detection parameters employed with a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer that is interfaced to a high magnetic field electrospray ionization (ES11 source are presented. ES1 occurs at atmospheric pressure in a 1.5-T field, and FTICR detection occurs 25 cm away at 3.0 T in either one of two cells separated by a conductance limit and maintained at pressure differentials of 5 * 10(5) and 2 * 10(7) torr, respectively. The continuous electrospray ion current traversing the high- and low-pressure cells is 350 and 100 pA, respectively. Retarding grid studies at the high-pressure cell indicate electrospray ion kinetic energies are controllable from less than an electronvolt to more than 10 eV. These kinetic energies are a function of desolvating capillary-skimmer assembly distance and the skimmer potential. Efficient accumulation of injected ions is accomplished only when the trap-plate potential matches the ion kinetic energy. If this condition is satisfied, the trapped ion cell fills to the ion space charge limit within a few hundred milliseconds. It is concluded that even at the high pressures used, the primary trapping mechanism cannot be solely collision dependent because the rate of ion accumulation is independent of background pressure. However, optimized FTICR excitation conditions for peptides and proteins in the mass range from 10(3) to more than 10(6) kDa are found to vary strongly with pressure; this is attributed to large mass- and charge-dependent differences in ion-molecule collision frequency. PMID- 24234566 TI - Gas-phase proton transfer reactions involving multiply charged cytochrome c ions and water under thermal conditions. AB - Investigations of gas-phase proton transfer reactions have been performed on protein molecular ions generated by electrospray ionization (ESI). Their reactions were studied in a heated capillary inlet/reactor prior to expansion into a quadrupole mass spectrometer. Results from investigations involving protonated horse heart cytochrome c and H, O suggest that Coulombit effects can lower reaction barriers as well as aid in entropically driven reactions. For example, the charge state distribution observed by a quadrupole mass spectrometer for multiply protonated cytochrome c without the addition of any reactive gas ranges from 9+ to 19+ , with the [M + 15H](15+) ion being the most intense peak. With the addition of H2O (proton affinity approximately 170.3+/-2 kcal/mol) to the capillary reactor at 120 degrees C, the charge state distribution shifts to a lower charge, ranging from 13+ to less than 9+. Under the same conditions with argon (proton affinity approximately 100 kcal/mol) as the reactive gas, no shift in the charge state distribution is observed. The results demonstrate that proton transfer to water can occur for highly protonated molecular ions, a process that would be expected to be highly endothermic for singly protonated molecules (for which Coulombic destabilization is not significant). The results imply that the charge state distribution from ESI is somewhat dependent upon the mechanism and speed of the droplet evaporation/ion desolvation process, which may vary substantially with the ESI/mass spectrometry interface design. PMID- 24234567 TI - Isomerization of linear C3H 3 (+) in its reaction with acetylene, and collisional stabilization of the [C5H 5 (+) ] (*) collision complex in a quadrupole ion trap mass spectrometer. AB - The isomerization of linear C3H 3 (+) in its reaction with acetylene to cyclic C3H 3 (+) was studied with a quadrupole ion trap mass spectrometer. The reaction of linear C3H 3 (+) with (13)C2H2 shows that isomerization takes place via a [C5H 5 (+) ](*) activated complex that is unstable relative to disproportionation back into the cyclic and linear forms of C3H 3 (+) and acetylene. The formation of carbon-13 labeled cyclic and linear C,Hi indicates that isomerization involves skeletal exchange. Collisional stabilization of the [C5H 5 (+) ](*) collision complex was achieved at a helium pressure of approximately 1 mtorr. PMID- 24234568 TI - Improved detection limits for fast atom bombardment mass spectrometry: A study of time-dependent desorption using a model pulsed bombardment ionization method. AB - Certain sample preparations for fast atom bombardment (FAB) yield an intense but brief pulse of sample ions at the onset of ionization. A model system is used to study this phenomenon. This system utilizes a conventional source of a constant flux of fast atoms and a probe that permits mechanical movement of the sample stage. This is used to simulate the effect of pulsing the atom beam. Experiments with model samples and selected ion monitoring detection show that, following bombardment initiation, sample ions are preferentially desorbed with respect to ions from the FAB matrix. Exhibition of preferential sample desorption depends upon the analyte behaving as a surfactant in the selected matrix. When used in conjunction with an array detector that permits data collection in a time resolved manner, this system allows collection of useful mass spectra with significantly enhanced sensitivity compared to normal bombardment. When applied to the undecapeptide eledoisin (sequence pyro-EPSKDAFIGLM-NH2, MW 1187.6 Da) this novel methodology allows an improvement in detection limit of at least three to four orders of magnitude over that observed when using conventional continuous FAB and a point detector. PMID- 24234569 TI - Origin of the tailing signal on the low-energy side of the main beam in mass analyzed ion kinetic energy spectra. AB - The tailing signal on the low-energy side of the precursor ion signal observed during fast atom bombardment (FAB) mass-analyzed ion kinetic energy spectrometric (MIKES) analyses is due largely to ions of higher m/z value than the chosen precursor. The majority of these ions are independent, unfragmented species that emerge from the ion source with less than the full amount of kinetic energy predicted by the source potential. The tailing precursor ion signal observed under helium collision-activated decomposition conditions is too short to account for the protracted MIKES tail (as judged from mass-to-charge ratio-deconvoluted MIKES analyses performed on a BEqQ hybrid instrument), and a tailing precursor signal is not observed under unimolecular decomposition conditions. Measurements of the mass-to-charge ratios of the ionic species comprising the MIKES tail demonstrated that ions higher in mass-to-charge ratio than the chosen precursor are present throughout the tail, with the mass-to-charge ratio increasing as kinetic energy decreases. These ions possess the same momentum as the chosen precursor, and thus were formed prior to the magnetic field. The existence of intact, source-formed [M + H](+) ions with reduced kinetic energy was demonstrated through several types of tandem mass spectrometric experiments. These [M + H](+) ions with reduced kinetic energy do not appear to have undergone collisional deceleration, because they do not possess increased internal energy (as judged by observation of their fragmentation patterns). The kinetic energy profiles of unfragmented FAB-desorbed ions were determined and found to exhibit a tailing character similar in appearance to that of the MIKES tail. The population of ions emerging from the source under FAB conditions thus incorporates the characteristics necessary to account for the MIKES tail, namely, the presence of ions of a mass-to-charge ratio higher than the chosen precursor (due to matrix and other background ions), which possess reduced kinetic energy such that their momentum is identical to that of the selected precursor. These ions may arise via desolvation and declustering processes in the acceleration region of the ion source, or via FAB or chemical ionization processes in regions removed from the FAB target. PMID- 24234570 TI - Fast atom bombardment mass spectrometry of Mycobacterial glycopeptidolipid antigens: Structural characterization by charge remote fragmentation. AB - Mycobacteria contain species- and type-specific antigens. Among them, glycopeptidolipids are present in medically relevant organisms belonging to Mycobacterium avium or M. fortuitum complexes. Fast-a tom bombardment mass spectrometry of glycopeptidolipids has proven to be difficult. In this article the cationization method with a metanitrobenzyl alcohol matrix, doped with sodium iodide, is described for analyzing these molecules. The molecular weight of the intact glycopeptidolipids was successfully determined and, using mass-analyzed ion kinetic energy spectrometry, the complete sequences of the peptide and saccharide moieties were elucidated. Moreover, the two structural variants present in these molecules were clearly differentiated. Application of the method showed that the same structural variant occurs in the glycopeptidolipids from two serologically related species of the M. fortuitum complex. PMID- 24234571 TI - Mass transport and calibration in liquid chromatography particle beam mass spectrometry. AB - Differences in the designs of two liquid chromatography particle beam mass spectrometry systems result in differences in the transport of ammonium acetate and differences in ion abundance-enhancing carrier effects. The effect of mobile phase composition, especially the proportion of water in the mobile phase, on transport efficiency is described. Instrument detection limits for 12 compounds with two different interface designs are presented. The calibrations are generally nonlinear explained in terms of mass transport effects and supported by experiments with isotopically labeled species that coelute with the native species. Summary results of a small multilaboratory study are presented. Calibration with isotopitally labeled internal standards is recommended for real world environmental samples. PMID- 24234572 TI - The mass spectrometry of taxol. AB - The antitumor agent taxol has been examined by electron ionization, chemical ionization, and fast atom bombardment mass spectrometry. Three ion series are observed: (1) the M-series, characteristic of the intact molecule; (2) the T series, with fragments derived from the taxane ring; and (3) the S-series representing the C-13 side chain. Neutral losses dominate each series of ions and serve to verify the presence and number of functionalities in each portion of the molecule. Fragmentation pathways and mechanisms of ion formation are proposed on the basis of product ion analysis and accurate mass measurements. PMID- 24234573 TI - Evidence of isomerization during ion isolation in the quadrupole ion trap. AB - Evidence of ion isomerization during isolation in an ion trap mass spectrometer is presented. An ion-molecule reaction that is specific for the tolyl cation was used to monitor the relative abundance of this species. In particular, it has been observed that ion isolation in the ion trap can impart sufficient energy to the tolyl cation to cause it to isomerize to a form (presumably either the benzyl or the tropylium ion) that is not reactive with the neutral reagent. These results are important to consider in ion trap applications involving ion species having activation barriers for isomerization lower than the activation barriers for dissociation. PMID- 24234575 TI - Systemic antimicrobial prophylaxis for percutaneous endoscopic gastrostomy. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a surgical procedure performed to maintain nutrition in the short- or long-term. During the procedure, a feeding tube that delivers either a liquid diet, or medication, via a clean or sterile delivery system, is placed surgically through the anterior abdominal wall. Those undergoing PEG tube placement are often vulnerable to infection because of age, compromised nutritional intake, immunosuppression, or underlying disease processes such as malignancy and diabetes mellitus. The increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) contributes both an additional risk to the placement procedure, and to the debate surrounding antibiotic prophylaxis for PEG tube placement. The aim of surgical antimicrobial prophylaxis is to establish a bactericidal concentration of an antimicrobial drug in the patient's serum and tissues, via a brief course of an appropriate agent, by the time of PEG tube placement in order to prevent any peristomal infections that might result from the procedure. OBJECTIVES: To establish whether prophylactic use of systemic antimicrobials reduces the risk of peristomal infection in people undergoing placement of percutaneous endoscopic gastrostomy tubes. SEARCH METHODS: In August 2013, for this third update, we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid Medline; Ovid Medline (In-Process & Other Non-Indexed Citations); Ovid Embase; and EBSCO CINAHL. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the use of prophylactic antimicrobials during PEG tube placement, with no restrictions regarding language of publication, date of publication, or publication status. Both review authors independently selected studies. DATA COLLECTION AND ANALYSIS: Both review authors independently extracted data and assessed study quality. Meta analyses were performed where appropriate. MAIN RESULTS: One new trial was identified and included in this update, bringing the total to 13 eligible RCTs, with a total of 1637 patients. All trials reported peristomal infection as an outcome. A pooled analysis of 12 trials resulted in a statistically significant reduction in the incidence of peristomal infection with prophylactic antibiotics (1271 patients pooled: OR 0.36, 95% CI 0.26 to 0.50). The newly identified trial compared IV antibiotics with antibiotics via PEG and could not be included in the meta-analysis. AUTHORS' CONCLUSIONS: Administration of systemic prophylactic antibiotics for PEG tube placement reduces peristomal infection. PMID- 24234577 TI - Provider, payor, and patient outcome expectations in back pain rehabilitation. AB - Return to work is used routinely to define successful back pain treatment. This study examined how the patient and three professional groups defined success for each of five categories of patients: not sponsored and working, sponsored and working, sponsored on modified duty, sponsored and off work for less than 10 weeks, and sponsored and off work for more than 10 weeks. The groups sampled were treating staff (n = 98), referring physicians (n = 98), third-party sponsors (n = 133), and patients (n = 648) representing all five patient categories. Each group provided a priority ranking for six objectives of treatment: Return to Work, Pain Control, Functional Improvement, Increased Strength and Range of Movement, Positive Attitude Shift, and Acquired Knowledge. The results indicated that the work status of the patient had a significant effect on the ranking of objectives by the treating staff and third-party sponsors. Physicians and patients considered pain control most important regardless of the patient category. Success in back pain rehabilitation is defined by different criteria. The determination of successful outcome must consider the patient's circumstances and acknowledge the perspective of the individual who is defining success. PMID- 24234576 TI - Association between pre-hypertension and cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. AB - BACKGROUND: The quantitative associations between prehypertension or its separate blood pressure (BP) ranges and the risk of main cardiovascular diseases (CVDs) have not been reliably documented. METHODS: We performed a comprehensive search of PubMed (1966 to June 2012) and the Cochrane Library (1988 to June 2012) without language restrictions. Prospective studies were included if they reported multivariate-adjusted risk ratios (RRs) and corresponding 95 % confidence intervals (CIs) of desirable outcomes, including fatal or non-fatal incident stroke, coronary heart disease, myocardial infarction (MI) or total CVD events, with respect to prehypertension or its separate BP ranges (low range: 120-129/80 84 mmHg; high range: 130-139/85-89 mmHg) at baseline with normal BP (<120/80 mmHg) as reference. Pooled RRs were estimated using a random-effects model or a fixed-effects model. RESULTS: Twenty-nine articles met our inclusion criteria, with 1,010,858 participants. Both low-range and high-range prehypertension were associated with a greater risk of developing or dying of total CVD (low-range: RR: 1.24; 95 % CI: 1.10 to 1.39; high range: RR: 1.56; 95 % CI: 1.36 to 1.78), stroke (low-range: RR: 1.35; 95 % CI: 1.10 to 1.66; high-range: RR: 1.95; 95 % CI: 1.69 to 2.24) and myocardial infarction (MI) (low range: RR: 1.43; 95 % CI: 1.10 to 1.86; high range: RR: 1.99; 95 % CI: 1.59 to 2.50). The whole range prehypertension had a 1.44-fold (95 % CI: 1.35 to 1.53), 1.73-fold (95 % CI: 1.61 to 1.85), and 1.79-fold (95 % CI: 1.45 to 2.22) risk of total CVD, stroke, and MI, respectively. There was no evidence of publication bias. CONCLUSIONS: Prehypertensive patients have a greater risk of incident stroke, MI and total CVD events. The impact was markedly different between the low and high prehypertension ranges PMID- 24234578 TI - Factors related to outcome following a work hardening program. AB - The purpose of this study was to determine factors related to a return to work following the completion of a work hardening program. Data from the Workers' Compensation Board of Alberta Millard Rehabilitation Centre for 1527 discharges, collected over 22 months, were examined retrospectively. Factors related to return to work were compared bivariately using logistic regression procedures. A multiple logistic regression model for return to work was also determined. The principle predictor of return to work was job-attached status to the pre-injury employer. Other factors related to return to work were education, primary diagnosis, injury to admission time, job attachment to the pre-accident employer, employer's annual payroll, and vocational direction. Due to the strength of the association between job-attached status to the pre-injury employer and a return to work, it was concluded that attempts to maintain this relationship should be a priority for rehabilitation providers and insurance carriers. PMID- 24234579 TI - Isokinetic performance in low back pain patients: The predictive power of the Self-Efficacy Scale. AB - The Self-Efficacy Scale (SES) has been found to predict isokinetic performance better than anthropometric variables. This study tests the predictive power of SES further against other measures of efficacy expectancies as well as measures of depression and perceived disability. A group of 105 chronic back pain patients was administered Beck's Depression Inventory (BDI), SES, the Pain Self-Efficacy Questionnaire (PSEQ), and the Oswestry low back pain disability questionnaire (OSWESTRY). Total isokinetic work done was measured at slow, medium and high speeds, for which multiple regression models were fitted controlling for sex, age, weight and height. The results confirmed SES to be the best overall predictor of isokinetic performance. BDI was not significant as a predictor of isokinetic performance. The models also revealed that SES predicts less well with increases in the test speed, particularly in extension. These results provide further evidence of the diagnostic value of SES relative to OSWESTRY and PSEQ. PMID- 24234580 TI - Effects of chair design on back muscle fatigue. AB - The electromyographic activity of the paraspinal muscles were examined to investigate the effects of chair sitting on muscle activation patterns and muscle fatigue. Twenty-four subjects were studied on the Balans, Back Up, and standard office chairs during a seated writing task and standing while performing a standardized muscle fatigue assessment test. The results of the study indicate that in 87.5% of the comparisons at the L3 site, the Back Up chair has lower readings of muscular effort compared to the Balans and office chair. During the muscle fatigue testing, the greatest amount of fatigue was noted in those subjects who sat in the Back Up chair last. When the Back Up chair was first or second, the least amount of fatigue was observed. The sEMG results supports a biomechanical model. The ergonomics of the Balans and office chairs give the least amount of support to the low back, while the Back Up chair provides the greatest amount of support. It is suggested that adequate pelvic girdle support during seated tasks will lower the threshold of back fatigue and thus facilitate return to work for low back pain patients. PMID- 24234581 TI - Employee ergonomics training: Current limitations and suggestions for improvement. AB - Employee ergonomics training programs are increasingly being called upon as a strategy to reduce illness and injury in the workplace. A review of the literature on ergonomics training revealed a variety of methodologies and practices. Programs varied in structure, content and method of delivery. These variances, along with a number of obstacles purported to influence the acceptance and effectiveness of training programs, reflect some of the current limitations to effective ergonomics training. This paper recommends the application of adult education principles to improve program planning and training practices. PMID- 24234582 TI - Advances in post-mortem CT-angiography. AB - Performing a post-mortem multidetector CT (MDCT) scan has already become routine in some institutes of forensic medicine. To better visualize the vascular system, different techniques of post-mortem CT-angiography have been explored, which can essentially be divided into partial- and whole-body angiography techniques. Probably the most frequently applied technique today is the so-called multiphase post-mortem CT-angiography (MPMCTA) a standardized method for investigating the vessels of the head, thorax and abdomen. Different studies exist, describing its use for medicolegal investigations, and its advantages as well as its artefacts and pitfalls. With the aim to investigate the performance of PMCTA and to develop and validate techniques, an international working group was created in 2012 called the "Technical Working Group Post-mortem Angiography Methods" (TWGPAM). Beyond its primary perspective, the goals of this group include creating recommendations for the indication of the investigation and for the interpretation of the images and to distribute knowledge about PMCTA. This article provides an overview about the different approaches that have been developed and tested in recent years and an update about ongoing research in this field. It will explain the technique of MPMCTA in detail and give an outline of its indications, application, advantages and limitations. PMID- 24234583 TI - Advantage of 3D volumetric dosemeter in delivery quality assurance of dynamic arc therapy: comparison of pencil beam and Monte Carlo calculations. AB - OBJECTIVE: To evaluate the accuracy of pencil beam calculation (PBC) and Monte Carlo calculation (MCC) for dynamic arc therapy (DAT) in a cylindrically shaped homogenous phantom, by comparing the two plans with an ion chamber, a film and a three-dimensional (3D) volumetric dosemeter. METHODS: For this study, an in-house phantom was constructed, and the PBC and MCC plans for DAT were performed using iPlan(r) RT (BrainLAB(r), Heimstetten, Germany). The A16 micro ion chamber (Standard Imaging, Middleton, WI), Gafchromic(r) EBT2 film (International Specialty Products, Wayne, NJ) and ArcCHECKTM (Sun Nuclear, Melbourne, FL) were used for measurements. For comparison with each plan, two-dimensional (2D) and 3D gamma analyses were performed using 3%/3 mm and 2%/2 mm criteria. RESULTS: The difference between the PBC and MCC plans using 2D and 3D gamma analyses was found to be 7.85% and 28.8%, respectively. The ion chamber and 2D dose distribution measurements did not exhibit this difference revealed by the comparison between the PBC and MCC plans. However, the 3D assessment showed a significant difference between the PBC and MCC (62.7% for PBC vs 93.4% for MCC, p = 0.034). CONCLUSION: Evaluation using a 3D volumetric dosemeter can be clinically useful for delivery quality assurance (QA), and the MCC should be used to achieve the most reliable dose calculation for DAT. ADVANCES IN KNOWLEDGE: (1) The DAT plan calculated using the PBC has a limitation in the calculation methods, and a 3D volumetric dosemeter was found to be an adequate tool for delivery QA of DAT. (2) The MCC was superior to PBC in terms of the accuracy in dose calculation for DAT even in the homogenous condition. PMID- 24234584 TI - Virtual anthropology and forensic identification using multidetector CT. AB - Virtual anthropology is made possible by modern cross-sectional imaging. Multislice CT (MSCT) can be used for comparative bone and dental identification, reconstructive identification and lesion identification. Comparative identification, the comparison of ante- and post-mortem imaging data, can be performed on both teeth and bones. Reconstructive identification, a considerable challenge for the radiologist, identifies the deceased by determining sex, geographical origin, stature and age at death. Lesion identification combines virtual autopsy and virtual anthropology. MSCT can be useful in palaeopathology, seeking arthropathy, infection, oral pathology, trauma, tumours, haematological disorders, stress indicators or occupational stress in bones and teeth. We examine some of the possibilities offered by this new radiological subspeciality that adds a new dimension to the work of the forensic radiologist. A multidisciplinary approach is crucial and involves communication and data exchange between radiologists, forensic pathologists, anthropologists and radiographers. PMID- 24234586 TI - Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders. AB - Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders. PMID- 24234585 TI - Clinical and research applications of simultaneous positron emission tomography and MRI. AB - Evaluation of the molecular processes responsible for disease pathogenesis and progression represents the new frontier of clinical radiology. Multimodality imaging lies at the cutting edge, combining the power of MRI for tissue characterization, microstructural appraisal and functional assessment together with new positron emission tomography (PET) tracers designed to target specific metabolic processes. The recent commercial availability of an integrated clinical whole-body PET-MRI provides a hybrid platform for exploring and exploiting the synergies of multimodal imaging. First experiences on the clinical and research application of hybrid PET-MRI are emerging. This article reviews the rapidly evolving field and speculates on the potential future direction. PMID- 24234587 TI - Helicobacter pylori seropositivities and risk of pancreatic carcinoma. AB - BACKGROUND: Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common. METHODS: We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays. RESULTS: Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index. CONCLUSIONS: Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma. IMPACT: H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site. PMID- 24234589 TI - Liberalism, authority, and bioethics commissions. AB - Bioethicists working on national ethics commissions frequently think of themselves as advisors to the government, but distance themselves from any claims to actual authority. Governments however may find it beneficial to appear to defer to the authority of these commissions when designing laws and policies, and might appoint such commissions for exactly this reason. Where does the authority for setting laws and policies come from? This question is best answered from within a normative political philosophy. This paper explains the locus of moral authority as understood within one family of normative political theories- liberal political theories--and argues that most major "liberal" commentators have understood both the source and scope of ethics commissions' authority in a manner at odds with liberalism, rightly interpreted. The author argues that reexamining the implications of liberalism for bioethics commissions would mean changing what are considered valid criticisms of such commissions and also changing the content of national bioethics commission mandates. The author concludes that bioethicists who participate in such commissions ought to carefully examine their own views about the normative limits of governmental authority because such limits have important implications for the contribution that bioethicists can legitimately make to government commissions. PMID- 24234588 TI - Predictive value of CYP3A and ABCB1 phenotyping probes for the pharmacokinetics of sunitinib: the ClearSun study. AB - BACKGROUND AND OBJECTIVE: The wide inter-patient variability in drug exposure partly explains the toxicity and efficacy profile of sunitinib treatment. In this prospective study cytochrome P450 (CYP) 3A and adenosine triphosphate binding cassette (ABC) B1 phenotypes were correlated to the pharmacokinetics of sunitinib and its active metabolite N-desethylsunitinib. METHODS: A correlation analysis was performed between sunitinib pharmacokinetics and 1'OH-midazolam/midazolam ratio and parameters derived from technetium-99m-2-methoxy isobutyl isonitrile ((99m)Tc-MIBI) scans, respectively. A population pharmacokinetic model using non linear mixed-effects modeling software NONMEM was built, which included the phenotype tests as covariate. RESULTS: In 52 patients, the mean trough concentration of sunitinib plus metabolite increased from 21.4 ng/mL at day 1 of a cycle to 88.1 ng/mL in the fourth week of treatment. A trend for a correlation was observed between (99m)Tc-MIBI elimination constant and trough concentrations of N-desethylsunitinib; however, this was not significant. Correlations were found between 1'OH-midazolam/midazolam ratio and sunitinib clearance (P = 0.008) and day 1 N-desethylsunitinib trough concentrations (P = 0.005), respectively. Moreover, patients suffering from grade 3 toxicities had significant lower clearance of sunitinib than patients without grade 3 toxicities (34.4 vs. 41.4 L/h; P = 0.025). CONCLUSIONS: Phenotype tests for ABCB1 and CYP3A4 did not explain inter-individual variability of sunitinib exposure sufficiently. However, the correlation between sunitinib clearance and the occurrence of severe toxicity suggests a direct exposure-toxicity relationship. PMID- 24234590 TI - Sluggish cognitive tempo (concentration deficit disorder?): current status, future directions, and a plea to change the name. AB - Symptoms of sluggish cognitive tempo (SCT) have been recognized for nearly 30 years as comprising a semi-independent set(s) of symptoms from the inattentive (IN) and hyperactive-impulsive (HI) symptoms involved in attention deficit/hyperactivity disorder (ADHD). It has only been within the past decade that research focusing specifically on SCT symptoms and on samples of SCT cases chosen independently from ADHD samples has increased so as to address the question of whether SCT is a distinct condition from ADHD or other disorders. All but two of these studies have focused on children but the two extant large scale studies on adults have replicated those findings. This Commentary highlights not only those findings concerning SCT that appear to be relatively robust, but also those patterns that appear to be emerging yet in need of further research to corroborate their association with SCT, as well as those barely or unexplored areas that may deserve more research. Evidence to date, including the many findings in this special issue, is nearing a critical mass that likely supports the conclusion that SCT is a distinct disorder of attention from ADHD, yet one that may overlap with it in about half of all cases. SCT has unique symptom dimensions and comorbidities from ADHD, probably distinct though lesser domains of impairment and demographic correlates, and perhaps unique cognitive deficits, causes and life course risks. These latter areas, however, are in need of substantially more research as is SCT in adults and treatments specifically designed for cases of SCT. Meanwhile, the name of the condition is premature, implying a known cognitive deficit that is as yet unknown, and is proving derogatory and offensive to patients, leading this author to recommend a change to Concentration Deficit Disorder. PMID- 24234591 TI - Dishevelled-1 (Dvl-1) protein: a potential participant of oxidative stress induced by selenium deficiency. AB - Oxidative stress induced by selenium deficiency has been shown to be associated with cardiovascular diseases. Nevertheless, the mechanism associated with oxidative stress induced by selenium deficiency is poorly understood. In the present study, 36 weaning C57BL/6 mice were randomly divided into 4 groups as follows: control (n =9), 4-week selenium deficiency (n =9), 8-week selenium deficiency (n = 9), and 12-week selenium deficiency (n =9). The levels of myocardial glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by Western blotting or commercial kits. Real-time PCR was performed to detect the mRNA expression of dishevelled-1 (Dvl 1) protein. Western blotting was conducted to evaluate the protein expression levels of Dvl-1 and beta-catenin. Our results demonstrated that the levels of GPx and SOD were significantly reduced, along with an increase in MDA in selenium deficient mice. Importantly, Dvl-1 and beta-catenin were clearly upregulated under oxidative stress. Collectively, our findings indicate that Dvl-1 may be an underlying participant of oxidative stress induced by selenium deficiency. PMID- 24234592 TI - Chronic sorrow: A content analysis of parental differences. AB - Sixty-eight mothers and 64 fathers of children with a neural tube defect responded to a questionnaire about chronic sorrow. Mothers reported a mood state change in very intense category from more pessimistic at time of diagnosis to more optimistic at current time. Fathers, although indicating a mood change in the very intense category to more optimistic, also had more pessimistic responses. Parental similarities and differences were also reported in both times and events that triggered the sorrow response. Categories across times and events were primarily related to health care, school/development concerns and social significance. Clinical and research implications of these findings are discussed. PMID- 24234593 TI - Pre-screening education in multiple marker screening programs: The effect on patient anxiety and knowledge. AB - Previous studies have shown that unexplained deviations in maternal serum multiple marker screening (MMS) generate considerable anxiety during the remainder of pregnancy. While the role of education in decreasing anxiety is documented, to date there has been no prospective evaluation of which educational practices might minimize this emotional stress. In a pilot study, we prospectively examined the effects on anxiety and knowledge by providing information about MMS (1) by genetic counselor, (2) by pamphlet, and (3) by primary physician. Women randomized to one of these three modalities were administered the Spielberger State- Trait Anxiety Inventory [STAI] and knowledge questionnaires at their initial obstetrics visit, at their second visit after educational intervention and 1-2 weeks after MMS results were provided to patients. Education resulted in an increase in knowledge and post-education knowledge was different between educational modalities. Anxiety declined in patients educated through genetic counseling or a pamphlet. PMID- 24234594 TI - Amniocentesis. PMID- 24234595 TI - Letters to the editor. PMID- 24234596 TI - Elasmobranch pericardial function. 1. Pericardial pressures are not always negative. AB - Acute studies have led to the generalization that negative pericardial pressure is necessary for optimal cardiac function in elasmobranchs. We chronically instrumented horn sharks with pericardial catheters to test the hypothesis that ejection of pericardial fluid through the pericardioperitoneal canal (PPC) during routine handling could have accounted in part for previous measurements of exclusively negative pressures (-0.3 to -9.1 cm H2O) in elasmobranchs. Maximum and minimum pericardial pressures measured immediately following routine handling (acute pressures) were more negative than those measured in resting horn sharks at intervals from 1 to 27 days following handling (chronic pressures). Chronic pericardial pulse pressure was less than acute. Entirely positive pericardial pressures were observed on occasion. Handling of chronically catheterized horn sharks resulted in ejection of 21 per cent (range=10-26, n=5) of the initial pericardial fluid volume through the PPC and reduced pericardial pressure. Operating pericardial fluid volume of horn sharks averaged 2.0 ml.kg(-1) (range=1.6-2.6, n=9). The PPC opened after 4.3+/-0.2 ml.kg(-1) (x+/-S.E.) of elasmobranch saline had been slowly infused into the pericardium, corresponding to an average pressure of 1.3+/-0.2 cm H2O (n=10). The presence of the PPC plus a comparatively large pericardial fluid volume allows horn sharks to regulate pericardial pressure. Our analysis of pericardial pulse pressure, which can be an index of cardiac activity, suggests in contrast to previous studies that the elasmobranch heart can have relatively high stroke volumes at pericardial pressures near ambient. Thus, for venous return in resting or even moderately active elasmobranchs, it is more important that pericardial pressure be pulsatile than at a mean level which is negative. PMID- 24234597 TI - Dietary carbohydrate and growth, body composition and heat increment in rainbow trout (Salmo gairdneri). AB - A study was conducted to determine growth, body composition and heat increment (HI) of rainbow trout reared on isonitrogenous high digestible carbohydrate (HC) and high fat (HL) diets at 15 degrees C. Trout reared on the HC diet had a significantly lower final body weight and carcass lipid content and a significantly higher feed:gain ratio and carcass protein content than trout reared on the HL diet after 12 weeks on the test diets. The lower carcass lipid composition indicates that trout do not readily convert dietary carbohydrates into fat. HI of trout reared on the HC diet was significantly higher than that of fish reared on the HL diet. Considering the poor utilization of dietary carbohydrates as an energy source and the apparently low conversion of dietary glucose into fat, the cause of the higher HI associated with the HC diet is not completely understood. However, it is possible the elimination of excess dietary glucose is an energy dependent process resulting in an increased heat production which would partly account for the increased HI. Furthermore, if the HC diet is a low net energy diet, then the metabolism and utilization of dietary and tissue proteins (amino acids) for energy by the trout may also be partly responsible for the increased HI of the trout reared on the HC diet. PMID- 24234598 TI - The thiamin deficiency signs and requirement of rainbow trout (Salmo gairdneri, Richardson). AB - Four growth studies were conducted to determine the signs, biochemical indices and histopathology of a thiamin deficiency and the thiamin requirement of young rainbow trout reared at 15 degrees C on a semi-purified test diet. The major overt signs of a thiamin deficiency in rainbow trout are predominantly neurological: irritability and instability. Other signs include convulsions, feed refusal, dark pigmentation and finally mortalities. Growth reduction in the thiamin deficient trout appear to result from anorexia or feed refusal and not specifically to a thiamin deficiency. Although there were prominant neurological signs in the thiamin deficient trout, there were no histopathological signs in any tissues of the trout, including the brain and central nervous system, examined by light microscopic techniques. The tissue transketolase activity would appear to be a sensitive and specific indicator of the thiamin status in the trout. In addition, the levels of plasma lactate and serum pyruvate are also elevated in thiamin deficient trout. On the basis of the growth parameters, absence of deficiency signs and kidney and liver transketolase activity, the thiamin requirement of rainbow trout reared at 15 degrees C on a semi-purified test diet is 1 mg/kg feed. PMID- 24234599 TI - Cytochrome P-450-dependent metabolism in isolated liver cells from fed and starved rainbow trout,Salmo gairdneri. AB - The cytochrome P-450 content in liver cells from rainbow trout was not affected by starvation for 12 weeks whereas the rate of cytochrome P-450-dependent deethylation of 7-ethoxycoumarin in liver cells from 6 or 12 weeks starved fish was 60% of the rate in fed fish. Treatment of fish with beta-naphthoflavone increased the 7-ethoxycoumarin metabolism several-fold in both starved and fed fish.Optimal cytochrome P-450 monooxygenation in liver cells from fed or starved fish was not affected by addition of glucose or 2-bromooctanoate, an inhibitor of fatty acid beta-oxidation which is the main source of metabolic fuel in trout liver. The cellular content of NADPH, an obligatory cofactor for cytochrome P-450 monooxygenation, was not affected by addition of substrate to cytochrome P-450, inhibition of fatty acid beta-oxidation or inhibition of the oxidative phosphorylation. This indicates a great capacity of rainbow trout liver cells to retain high NADPH/NADP(+) ratios. These results suggest that the cytochrome P-450 mediated metabolism of xenobiotics in liver cells from fed or starved trout is not limited by the availability of reducing equivalents. PMID- 24234600 TI - Cortisol and liver metabolism of immature American eels,Anguilla rostrata (LeSueur). AB - Plasma and liver composition, liver enzyme activities, and metabolite flux in isolated hepatocytes have been studied in immature American eels,Anguilla rostrata, injected daily IP with saline or cortisol (0.35 mg/kg eel). Plasma cortisol values were significantly increased above saline controls in those eels receiving cortisol at 3h and 6h following the final (tenth) injection. On day 6 and 10 of injection plasma cortisol levels were significantly below saline controls 24h following cortisol injection. Plasma glucose values were significantly depressed in the cortisol-injected eels at both 6 and 24h following the final (tenth) injection. At the 24h sampling time, plasma protein had significantly increased, but there was no change in either plasma amino acid or fatty acid levels. An increased hepatosomatic index was attributed to a major increase in total lipids, as both protein and glycogen contents were decreased. Of the liver enzymes assayed, significant activity changes occurred only for lactate dehydrogenase (decreased), mitochondrial citrate synthase (increased) and phosphoenolpyruvate carboxykinase (increased) 24h following the final (tenth) cortisol injection. Although enzyme activity changes implied increased liver gluconeogenesis, the absolute rate of lactate, alanine, and aspartate incorporation into glucose declined in viable hepatocytes isolated from cortisol injected eels compared to the saline controls. Relative changes in metabolite flux did support a preferential increase in gluconeogenesis from amino acids. These results are consistent with the increase in amino acid gluconeogenesis as a result of cortisol administration implied in previous studies, but failed to show a definitive cortisol effect on this pathway in the eel liver. It is suggested that other hormones (e.g. thyroxine, catecholamines, glucagon) may interact in a complex way with cortisolin vivo to bring about the biochemical changes observed in this study. The rapid clearance of exogenously injected cortisol noted in this study makes causal relationships between the injected hormone and any observed metabolic effect in the intact animal difficult. PMID- 24234603 TI - SergioFACCHETTI: Institutions Active in Environmental Science, Research and Technology in Italy(ESPR 1/4, 280-283, 1994). PMID- 24234602 TI - Bioavailability and total content as measures of pollution? PMID- 24234604 TI - Issue: Request for information on incineration of useless pesticides: Possible emissions, reactions in atmosphere, water and soil, effects on the population; conditions for measuring the emissions; alternativesversus incineration. PMID- 24234601 TI - Depression treatment enhances adherence to antiretroviral therapy: a meta analysis. AB - BACKGROUND: Depression is a risk factor for nonadherence to HIV/AIDS treatment. PURPOSE: A meta-analysis was conducted to examine whether treatment of depression and psychological distress improves antiretroviral therapy adherence. METHODS: PubMed and PsycINFO databases were systematically searched for relevant articles. Studies that reported an association between depression treatment (or an intervention with a component addressing mental health) and antiretroviral adherence were included. RESULTS: Across 29 studies of 12,243 persons living with HIV/AIDS, treatment of depression and psychological distress improved antiretroviral adherence (p < 0.001). The odds of a person adhering were 83 % better if he/she was treated for depression. Greater improvements in adherence were found for samples with lower CD4 counts or more severe depression, for interventions specifically targeting depression (versus addressing mental health as a secondary objective), longer treatments, and observational studies. CONCLUSIONS: These findings support the need for detection and treatment of depression among persons living with HIV/AIDS. PMID- 24234605 TI - Lithuanian Green Movement (LGM). AB - The Lithuanian Green Movement (LGM) was established in the Autumn of 1988. The LGM is an umbrella union of environmental clubs, groups and individuals for common activities, coordination and exchange of information. The LGM is a non profit making and non-governmental organization. PMID- 24234606 TI - Nanoparticles open up a world of new materials. PMID- 24234607 TI - The environmental technology market in Korea. PMID- 24234608 TI - Substance flows through the economy and environment of a region : Part II: Modelling. AB - In the tradition of the study of materials flows through society, the Substance Flow Analysis (SFA) method and its software tool SFINX are presented. SFA aims at providing the relevant information for a country's overall management strategy regarding single substances or coherent groups of substances. Three modelling techniques and their possibilities and limitations are discussed: Bookkeeping, static modelling, and dynamic modelling. The computer program SFINX can be used for varoius purposes: (1) to obtain an overview of stocks and flows of a substance in, out and through a nation's economy and environment for a specific year, (2) to trace the origins of specific pollution problems, and (3) to estimate the effectiveness of certain abatement measures. Each application has its own requirements with regard to data and modelling. PMID- 24234609 TI - Cadmium and methylmercury bioaccumulation by nymphs of the burrowing mayflyHexagenia rigida from the water column and sediment. AB - Based on a three compartment microcosm-water column, natural sediment,Hexagenia rigida nymphs-an experimental study was set up to compare cadmium (Cd) and methylmercury (MeHg) bioaccumulation by a burrowing mayfly species, after exposure via the water column or the sediment as initial contamination sources. Results from a wide concentration range for each exposure condition revealed very marked differences between the two metals: MeHg was readily accumulated from the two contamination sources, leading to important metal concentrations in the nymphs after the 2 weeks' exposure; Cd bioaccumulation, on the other hand, was negligible when the metal was added to the water compartment, even though significant transfers were observed from the sediment source. The average Cd concentrations in the nymphs were proportional to the sediment contamination levels. Turbidity measurements in the water column, reflecting the bioturbation activity of the nymphs, revealed that the effect of Cd was significant, but only when the metal was initially added to the sediment. The results are discussed according to the uptake routes and the structural and functional properties of the biological barriers involved (gills and gut). PMID- 24234610 TI - Octanol/water partition coefficients for environmentally important organic compounds : Test of three RP-HPLC-methods and new experimental results. AB - Partition coefficients PO,w ((i)) describing the distribution of a solute i onto coexisting phases of 1-octanol and water are needed in a large variety of applications. They can be measured directly by HPLC as long as log PO,w ((i))? 3.5. For more hydrophobic substances, several experimental procedures have been proposed in the literature. The reliability of those methods is questionable. Therefore, in the present work, PO,w ((i)) is determined experimentally by three HPLC methods using reversed-phase HPLC [1]. Results from different procedures are compared critically. The method of Braumann [2] proved to be superior over the OECD-guidelines [3]. It was therefore applied to determine octanol/water partition coefficients for 23 substances at 25 degrees C. For eight of those substances (4-methylindole; 9-(hydroxymethyl)anthracene; N-ethylcarbazol; ethylcyclohexane; trans-2-octene; l,l-dimethyl-(ethy])cyclohexane; heptylbenzene; 4-dodecyl-l,3-benzenediol) no experimentally determined number for PO,w ((i)) has been published before. PMID- 24234611 TI - Aluminium production as a source of atmospheric carbonyl sulfide (COS). AB - Carbonyl sulfide is found as a major sulfur compound in anodic gases of commercial aluminium electrolysis. Recent spectroscopic measurements on industrial aluminium smelters found typical CO/COS ratios between 80 and 200. This results in specific COS emissions of between 1 and 7 kg/t(Al) if all COS is released into the atmosphere. In 1993 aluminium production would have been responsible for between 0.02 and 0.14 Tg of COS emissions. Currently, aluminium production does not seem to influence the total atmospheric COS budget to an extent beyond its natural variability. If recent growth rates of global aluminium production are sustained, however, COS emissions would quadruple until 2030. Together with increasing aircraft emissions into the stratosphere, an increase of the sulfate background aerosol is to be expected that could significantly enhance ozone depletion. The use of inert anodes is recommended to reduce aluminium production emissions of COS and CF4, C2F6, CO2, and CO at the same time. PMID- 24234612 TI - Preface. PMID- 24234614 TI - UK report backs modern energy-from-waste plants. PMID- 24234613 TI - Field test of volatilization models. AB - Four volatilization models were tested against field data from the Manchester Ship Canal and the River Main. The equations byMACKAY andYEUN, using Schmidt number and wind speed for the calculation of volatilization rate, were found to give the best results for the slowly flowing Ship Canal. Models using flow velocity grossly underestimated the real values for this waterway but were found to be superior for the faster flowing River Main. The results of this work indicate that volatilization models should be carefully chosen for a particular environmental situation. Additionally, the importance of the validation of such models against field data is emphasised. PMID- 24234615 TI - The north sea : invisible decline? Greenpeace report* short version. PMID- 24234616 TI - Environmental chemistry of the heavy elements. PMID- 24234617 TI - Afriwaste The fixation and stabilisation of hazardous waste : Rendering waste into a product safe for landfills. AB - The disposal of hazardous and toxic wastes is an area where utmost care and responsibility needs to be exercised. A certain (and mostly acceptable) level of care and responsibility has been legislated and is in place in most developed economies (UK, USA, Canada, Europe, etc.). This is, however, generally not the case in under-developed or developing economies, South Africa being no exception.This paper reflects on various disposal methods and describes a potentially economic alternative to existing methods of the disposal of toxic and hazardous wastes. These existing methods are: Disposal in Class I landfill sites and destruction via incineration.Although incineration (which entails the total destruction of toxic compounds) is the preferred method of disposal, an alternative solution is the fixation of these wastes using specially formulated cementitious agents. The Fixation Solution can be economically feasible, especially in developing economies. PMID- 24234618 TI - Cleanable particulate filter for diesel engines. PMID- 24234619 TI - The microelectronic nose. PMID- 24234620 TI - Application of the criteria for classification of existing chemicals as dangerous for the environment. AB - The criteria for classification and labelling of substances as "dangerous for the environment" agreed upon within the European Union (EU) were applied to two sets of existing chemicals. One set (sample A) consisted of 41 randomly selected compounds listed in the European Inventory of Existing Chemical Substances (EINECS). The other set (sample B) comprised 115 substances listed in Annex I of Directive 67/548/EEC which were classified by the EU Working Group on Classification and Labelling of Existing Chemicals. The aquatic toxicity (fish mortality,Daphnia immobilisation, algal growth inhibition), ready biodegradability and n-octanol/water partition coefficient were measured for sample A by one and the same laboratory. For sample B, the available ecotoxicological data originated from many different sources and therefore was rather heterogeneous. In both samples, algal toxicity was the most sensitive effect parameter for most substances. Furthermore, it was found that, classification based on a single aquatic test result differs in many cases from classification based on a complete data set, although a correlation exists between the biological end-points of the aquatic toxicity test systems. PMID- 24234622 TI - 26th international symposium on environmental analytical chemistry vienna, austria 9-12 april 1996. PMID- 24234623 TI - Preserving leaves for tannin and phenolic glycoside analyses: A comparison of methods using three willow taxa. AB - Members of the Salicaceae often produce phenolic glycosides and condensed tannins. There is much debate on the best method for the preservation of leaf material prior to chemical analysis. Published results indicate freeze-drying, a method commonly used for tannin analysis, may be inappropriate for phenolic glycosides, unless done in a manner to prevent thawing during the drying process. Another commonly employed method, air-drying, is appropriate for phenolic glycosides but inappropriate for condensed tannins. I present evidence using willow leaves that demonstrates that: (1) leaves freeze-dried in external flasks without temperature control contain lower concentrations of phenolic glycosides (salicortin and 2'-cinnamoylsalicortin), (2) air-dried leaves have reduced concentrations of condensed tannins, while (3) vacuum-dried fresh leaves have high concentrations of both phenolic glycosides and condensed tannins. Freeze drying caused salicortin and 2'-cinnamoyl salicortin concentrations to drop by 20 mg/g and 4 mg/g, respectively. Salicin, a product of salicortin and 2'-cinnamoyl salicortin degradation, is absent in vacuum-dried leaves, present in air-dried leaves and very high in freeze-dried leaves. Thus, the presence of salicin in this system is an artifact of the preservation technique. Condensed tannin concentrations dropped nearly 20 mg/g when leaves were air-dried. Thus, vacuum drying fresh leaves allows researchers to quantify phenolic glycosides and condensed tannins from the same leaf material. PMID- 24234624 TI - Secondary chemistry of hybrid and parental willows: Phenolic glycosides and condensed tannins inSalix sericea, S. eriocephala, and their hybrids. AB - Salix sericea andS. eriocephala differ markedly in secondary chemistry.S. sericea produces phenolic glycosides, salicortin and 2'-cinnamoylsalicortin, and low concentrations of condensed tannin. In contrast,S. eriocephala produces no phenolic glycosides, but high concentrations of condensed tannins. Hybrid chemistry is intermediate for both types of chemicals, suggesting predominantly additive inheritance of these two defensive chemical systems from the parental species. However, there is extensive variation among hybrids. This variation may be due to genetic variation among parental genotypes, which genes were passed on, or to subsequent back-crossing. The differences in chemistry are likely to exert a strong effect on the relative susceptibility of hybrid and parental willows to herbivores. PMID- 24234625 TI - Antifeedant and toxic effects of sesquiterpenes fromSenecio palmensis to colorado potato beetle. AB - A bioassay-guided fractionation of the aerial parts ofSenecio palmensis resulted in the isolation of two sesquiterpenes, 2,10-bisaboladien-1-one and 11beta acetoxy-5-angeloyloxy-silphinen-3-one. The bisabolene and the silphinene represented 0.012% and 0.024% of the plant dry weight, respectively. Both compounds showed antifeedant activity againstLeptinotarsa decemlineata larvae and adults in short-term choice and no-choice bioassays. Both compounds were also tested against different species of phytopathogenic fungi. The beetles were more sensitive to these compounds in choice than in no-choice assays, with a gradient of increasing sensitivity from second instars to adults. Bisabolene was 45 times less active as an antifeedant than juglone, which was tested as a positive control. The silphinen was more active than the bisabolene, with a range of activity similar to juglone. Furthermore, exposure of fourth instars to these compounds over a 24-hr period resulted in reduced feeding and growth rates. To distinguish between antifeedant and toxic effects, growth efficiencies were calculated as the slope of the regression of relative growth rate on relative consumption rate. The comparison of these results with those of antifeedant simulation and contact toxicity bioassays indicates that feeding inhibition is the primary mode of action of the bisabolene, while the silphinene shows both antifeedant and toxic effects. PMID- 24234626 TI - Effects of benzoic and cinnamic acids on membrane permeability of soybean roots. AB - Benzoic (BEN) and cinnamic (CIN) acids are commonly found in soils and are considered as strong allelochemicals. Published information suggest that BEN and CIN and other phenolic acids decrease plant growth in part by suppressing nutrient absorption. However, studies on the mechanism of action were not conclusive. We examined the effects of BEN and CIN on the cell plasma membrane in intact soybean (Glycine max L. cv. Maple Bell) seedlings. Treating intact root systems with BEN or CIN rapidly increased electrolyte leakage and ultraviolet absorption of materials into the surrounding solution. After 12 hr of treatment, BEN and CIN lowered the extracellular sulfhydryl group content in roots. The two allelochemicals induced lipid peroxidation, which resulted from free radical formation in plasma membranes, inhibition of catalase and peroxidase activities, and sulfhydryl group depletion. Oxidation or cross-linking of plasma membrane sulfhydryl groups is the first mode of action of both compounds. The BEN- and CIN induced decrease in soybean nutrient absorption may be a consequence of damage to cell membrane integrity caused by a decrease in sulfhydryl groups followed by lipid peroxidation. PMID- 24234627 TI - Biological activity of chemicals identified from extracts and volatiles of maleRhagoletis cerasi. AB - Fractions obtained by chromatographic separation of extracts and volatiles from maleRhagoletis cerasi flies were tested for biological activity on females under laboratory conditions. During the bioassays, the number of incoming flies as well as the time spent by individual flies on the area of stimulus were taken under consideration. Two distinct types of female behavior were observed, i.e., attraction and arrestant behavior. GC-MS analysis of biologically active fractions resulted in tentative identification of 75 compounds. EAG screening for 27 of these compounds was performed, and subsequent laboratory bioassays resulted in the confirmation of arrestant activity for various mixtures of eight fatty acids (octadecanoic, nonadecanoic, eicosatetraenoic, eicosapenaenoic, eicosaenoic, heneicosanoic, docosahexenoic, and docosanoic). Following EAG tests and laboratory bioassays, a possible mode of chemical communication of this species with sex pheromones is proposed. PMID- 24234628 TI - Spatial distribution of pheromone in vineyards treated for mating disruption of the grape vine mothLobesia botrana measured with electroantennograms. AB - The spatial distribution of the pheromone of the grape vine moth.Lobesia botrana (Lepidoptera: Tortricidae), was measured in vineyards treated for mating disruption by using an electroantennogram technique (EAG). Five hundred dispensers per hectare, each containing 0.1 g of the main component of the sex pheromone (E,Z)-7,9-dodecadienyl acetate (E7,Z9-12: Ac) were evenly distributed in the experimental vineyards. The EAG amplitudes measured in the experimental plots were transformed into relative pheromone concentrations by means of a calibration curve. Mean relative pheromone concentrations in the center of a treated plot reached 2.31 * 10(-4) relative units. No significant differences in the mean relative pheromone concentrations were found between replicate plots (P > 0.01). The mean relative pheromone concentrations measured within one plot along a transect at 5-m intervals also showed no significant differences between the sites. These results indicate that inside the borders of treated areas the pheromone was evenly distributed. No sites with significantly lower pheromone concentrations, frequently assumed to be the cause for higher trap catches in some areas, were found. However, the mean relative pheromone concentration rapidly declined more than 100-fold outside the border of the treated plot. At 10 m from the treated area, the EAGs showed no significant difference compared to the EAGs recorded in an untreated area. A rapid drop in the mean relative pheromone concentration was also found on a vertical transect through the canopy of the vineyard. Measurements in an untreated control block gave a mean antennal response approximately 1000-fold lower than in a nearby pheromone treated plot. The significance of the variation in the pheromone distribution for the success of the mating-disruption method is discussed. PMID- 24234629 TI - Chemically mediated ovipositional behaviors of the european corn borer,Ostrinia nubilalis (Lepidoptera: Pyralidae). AB - The volatile plant sesquiterpenoids farnesene, nerolidol, and farnesol were tested to determine their effect on European corn borer,Ostrinia nubilalis, oviposition during the first six nights of the adult stage. Adult European corn borers were released into cages designed to encourage oviposition on eight glass plates randomly arranged on top of the cage: four coated with either 80ug/cm(2) farnesene, nerolidol, or farnesol, and four coated with the solvent methylene chloride. The setup was used as a binary choice test. Farnesene was preferred by females because they deposited significantly more egg masses on plates coated with the compound. Nerolidol had no effect. Farnesol, by contrast, deterred oviposition: the number of egg masses was significantly lower on plates covered with that compound. These data show that structural modification at a single terminal functional group in these compounds affects the ovipositional behavior of European corn borer females. PMID- 24234630 TI - Interfamily variation in comb wax hydrocarbons produced by honey bees. AB - The hydrocarbons of honeybee comb wax vary significantly between colonies. This variation is explained in part by genetic (familial) differences among colonies. Even though significant differences in wax hydrocarbons exist among families, there is a high level of consistency within and among families in a correlation analysis, indicating structural constancy in comb wax. The significance of these results in interpreting the potential role of comb wax in the nestmate recognition system of the honeybee is discussed. PMID- 24234631 TI - Platyphylloside: Metabolism and digestibility reductionin vitro. AB - The metabolism of platyphylloside [(5S)-5-hydroxy-1,7-bis-(4-hydroxyphenyl)-3 heptanone-5-O-beta-D-glucopyranosidel]-known to reduce digestibility-was studiedin vitro in sheep rumen liquor. Platyphylloside is hydrolyzed to 5-hydroxy 3-platyphyllone [(5S)-5-hydroxy-1,7-bis-(4-hydroxyphenyl)-3-heptanone], which is reduced to centrolobol [1,7-bis-(4-hydroxyphenyl)-3-heptanol], via 3 platyphyllone [7-bis-(4-hydroxyphenyl)-3-heptanone]. The digestibility-reducing effect was shown to be correlated with the concentration of centrolobol. PMID- 24234632 TI - Responses of beaver (Castor canadensis Kuhl) to predator chemicals. AB - Free-ranging beaver (Castor canadensis) in two different beaver populations in New York State were exposed to predator chemicals to test feeding inhibition. Solvent extracts of feces were applied to stem sections of aspen, the preferred food tree of beavers, permitting smelling and tasting the samples. Predator odors were from wolf (Canis lupus), coyote (Canis latrans), dog (Canis familiaris), black bear (Ursus americanus), river otter (Lutra canadensis), lynx (Lynx canadensis), and African lion (Panthera leo). The experiment was repeated. The predator odors reduced feeding compared to untreated or solvent-treated controls. One population consumed 17.0% of the samples with predator odor and 27.0% of the controls in summer, and 48.4% and 60.0%, respectively, in autumn. The other population accepted 3.15% of the predator odor samples and 11.05% of the controls in summer. Coyote, lynx, and river otter odors had the strongest effects. Diesel oil and bitter-tasting neem extract had weaker effects. Predator odors are promising as feeding repellents for beaver. PMID- 24234633 TI - Allelopathic potential ofAnthoxanthum odoratum for invadingZoysia-grassland in Japan. AB - The growth ofZoysia japonica surroundingAnthoxanthum odoratum onZoysia-grassland in Japan was investigated in June 1994. The stem density ofZ. japonica tended to decrease with short distances between twoA. odoratum plants. This showed that the growth ofZ. japonica surroundingA. odoratum was reduced. Basic, neutral, and acidic fractions extracted fromA. odoratum plants inhibited the seedling growth of lettuce. In particular the neutral fraction showed the strongest activity among the three fractions. The main inhibitory compound obtained atR f 0.6-0.7, on the thin-layer chromatogram of the neutral fraction, was isolated and identified as coumarin by means of GC-MS. Coumarin solution inhibited seedling growth ofZ. japonica in low concentrations but, conversely, promoted seedling growth ofA. odoratum. Coumarin was contained in all parts ofA. odoratum and its concentration varied with the season and from one individual plant to another. In particular, coumarin was highly concentrated in the leaves, accounting for more than 2.5% of dry leaf weight in June. The inhibitory effect of these aqueous extracts was correlated to the amount of coumarin inA. odoratum leaves and cournarin was considered to be the main inhibitory compound. PMID- 24234634 TI - Effects ofneo-clerodane diterpenes fromTeucrium on feeding behavior of colorado potato beetle larvae. AB - Treatment of potato leaf disks with fourneo-clerodane diterpenes fromTeucrium (eriocephalin, teucrin-A, teucvin, and teuscorolide) significantly reduced feeding by larvae ofLeptinotarsa decemlineata (Colorado potato beetle). Choice and no-choice tests suggest that teuscorolide acts as a feeding deterrent, whereas the antifeedant activity of teucrin-A, teucvin, and eriocephalin is likely associated with a toxic mode of action. Nutritional tests, antifeedant simulation assays, and posttreatment studies confirmed that teucrin-A can be categorized by its mode of action as a toxin, rather than as a feeding deterrent. PMID- 24234635 TI - Professor Al Nier and his influence on mass spectrometry. AB - Professor Alfred Otto Carl Nier has had a singular influence on the art and science of mass spectrometry over the last 55 years. I had the pleasure of conducting an oral history interview of Dr. Nier in the spring of 1989 at his office and laboratory at the University of Minnesota. I was assisted in this endeavor by Thomas Krick of the Biochemistry Department staff. The interview was underwritten by the American Society for Mass Spectrometry. The following highlights are excerpted from 10 1/2 hours of material recorded during the interview. The complete set of tapes, a full transcript, pictures, and other material collected during the interview are archived with the Beckman Center for the History of Chemistry in Philadelphia. PMID- 24234636 TI - A new approach for the study of gas-phase ion-ion reactions using electrospray ionization. AB - A simple flow reactor which facilitates the study and application of ion-ion and ion-molecule reactions at near atmospheric pressures is reported. Reactant ions were generated by electrospray ionization and discharge ionization methods, although any ionization sources amenable to atmospheric pressure may be used. Ions of opposite charge are generated in spatially separate ion sources and are swept into capillary inlets where the flows are merged and where reaction(s) can occur. Among the reactions investigated were the partial neutralization of multiply protonated polypeptides and proteins such as melittin, bradykinin, cytochrome c, and myoglobin by reaction with discharge-generated anions, the partial neutralization of multiply charged anions of oligodeoxyadenylic acid (d(pA)3) by reaction with discharge-generated cations, the partial neutralization of bovine A-chain insulin anions by reaction with myoglobin [M+nH](n+) ions, and the reaction of multiply protonated melittin with discharge-generated cations. The cation-anion reactions generally resulted in a shift to lower charge (higher mass-to-charge ratio) in the products' charge state distributions and the transfer of solvent molecules to the macromolecule products. Multiply protonated melittin was detected in a less highly solvated state with the positive discharge in operation. PMID- 24234637 TI - A pulsed ion deflection system for background reduction in (252)CF-plasma desorption mass spectrometry. AB - The use of an electrostatic particle guide (EPG) for background reduction in a time-of-flight mass spectrometer is described. Operating with reverse polarity, the EPG deflects ions radially from the beam axis, separating the ionic and neutral components of the beam. Use of the deflection EPG in a synchronized pulsed mode with a barrier disk aligned in the center of the beam axis eliminates up to 80% of the spectral background in the molecular ion region of an insulin spectrum obtained by (252)Cf-plasma desorption mass spectrometry. The background eliminated is due to the neutral products of metastable fragmentation and to uncorrelated events. Although peak intensities are reduced when the pulsed deflection EPG system is used, the reduction in background achieved is greater, resulting in an overall improvement in peak-to-background ratios of up to a factor of three. A new large-area stop detector designed for use with the pulsed deflection EPG is described. The new hybrid detector, which utilizes the combination of a large (75-mm active diameter) microchannel plate (MCP) and a scintillation detector, provides greater sensitivity for high-mass ions than a conventional MCP chevron detector. PMID- 24234638 TI - Probing trapped ion energies via ion-molecule reaction kinetics: Quadrupole ion trap mass spectrometry. AB - We present a detailed study of the energies of the ions stored in a quadrupole ion trap mass spectrometer (QITMS). Previous studies have shown that the rate constant, k, for the charge exchange reaction Ar(+) N(+) 2 ->, N(+) 2+Ar increases with increasing ion-molecule center-of-mass kinetic energy (K.E.cm). Thus, we have determined k for this chemical "thermometer" reaction at a variety of Ar and N2 pressures and have assigned K.E.cm values as a function of the q2 of the Ar(+) ion both with and without He buffer gas present in the trap. The K.E.cm energies are found to lie within the range 0.11-0.34 eV over the variety of experimental conditions investigated. Quantitative "cooling" effects due to the presence of He buffer gas are reported, as are increases in K.E.cm due to an increase in the q2 of the Ar(+) ion. "Effective" temperatures of the Ar(+) ions in He buffer are determined based on a Maxwell-Boltzmann distribution of ion energies. The resulting temperatures are found to lie within the range ~ 1700 3300 K. We have also examined the K.E.cm, values arising from the chemical thermometer reaction of O(+) 2 with CH4, as previous assignments of effective ion temperatures based on this reaction have been called into question. PMID- 24234639 TI - Probing trapped ion energies via ion-molecule reaction kinetics: Fourier transform ion cyclotron resonance mass spectrometry. AB - The kinetic energy-dependent Ar(+)+ N2 ion-molecule reaction has been used as a chemical "thermometer" to determine the kinetic energy of ions produced by electron ionization and trapped by using a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The rate constant for this reaction obtained on the FTICR mass spectrometer was compared to previous work, which allowed a kinetic energy estimate to be made. In addition, the effects of varying parameters such as trapping voltage and pressure on ion kinetic energy were investigated. No evidence of the differing reactivity of higher energy electronic states of Ar(+), such as (2)P1/2, was observed and the results of a model of this system are presented that support this observation. Pressure studies revealed that with an average of as few as 13 ion-molecule collisions, Ar(+) ions are collisionally relaxed to an extent unaffected by additional collisions. Based on recent variable temperature selected ion flow drift tube measurements, FTICR ion energies are estimated to be slightly above thermal. PMID- 24234640 TI - Space charge effects on relative peak heights in fourier transform-ion cyclotron resonance spectra. AB - Ion trajectory calculations have confirmed that space charge interactions can be a source for mass discrimination seen in Fourier transform-ion cyclotron resonance (FT-ICR) spectra. As compared with the previously recognized mechanism of z-axis excitation, ion-ion repulsion is a mechanism which specifically affects relative peak heights of ions close in mass, and is most severe for low excitation radiofrequency (rf) amplitudes. In this mechanism, Coulomb repulsion significantly perturbs the motion of the ion clouds during excitation and alters the final cyclotron orbital radii. Under these conditions peak heights do not accurately reflect the true ion abundances in the FT-ICR spectrometer. Mass discrimination can be minimized by using low numbers of ions, low ion densities, and a short, high amplitude rf excitation waveform. Experimental observation of the relative peak heights of the m/z 91, 92, and 134 ions in n-butylbenzene gives quantitative confirmation of the results of the trajectory calculations. Chirp, SWIFT, and impulse excitation were modeled: impulse excitation was found to be most effective in minimizing the effects of space charge interactions. PMID- 24234641 TI - Quadrupole-based mass spectrometric evaluation of isotope ratios of carbon dioxide in expired air from mice and men following the administration of (13)C methyl methionine. AB - A method is described for the measurement of the isotopic ratio of (13)CO2/(12)CO2 in expired air from individual mice and from humans by means of a quadrupole-based mass spectrometer system. Following the administration of (13)C methyl methionine or another appropriately labeled substrate, the (13)C portion of the molecule is converted to (13)CO2. The (13)CO2 enters the carbonate pool(s) and is ultimately eliminated in the expired air where it is available for analysis. The expired air is transported by a small pump from the subject to a digital valve which provides for the alternate influx of expired air and standard into the mass spectrometer for 30 or 60 seconds each, respectively. The inlet consists of a control valve connected to a microbore stainless steel tube, and can be adjusted manually to achieve a source pressure of 4 X 10(-5) torr. The correction factors for drift in sensitivity and in the mass axis are generated by repeated, automatic analysis of the running standard and relating those measurements to values generated for the standard during the first minutes of the experiment. Each measurement of an isotopic ratio in expired air is corrected by an amount determined by the standard immediately preceding it. Precision for the measurements of both sample and standard ratios is +/-0.2%. The technique should prove useful in assessing the metabolism, of substrates that are converted to CO2 and may find utility as a diagnostic tool for certain diseases and metabolic disorders. PMID- 24234642 TI - An investigation of dipeptides containing polar and nonpolar side groups by curie point pyrolysis tandem mass spectrometry. AB - Methionyl-leucine, leucyl-methionine, phenylalanyl-leucine, and leucyl phenylalanine have been analyzed to determine dipeptide fragmentation mechanisms in Curie-point pyrolysis tandem mass spectrometry. Results show that fragmentations of dipeptides follow two general pathways, one involving direct cleavage of the dipeptide and the other involving cyclization of the dipeptide. Unique products and strong changes in relative mass spectral peak intensities arise, depending on constituent amino acid residues and their sequence. Also, the length and nature of the side groups strongly direct fragmentation. From these results, the major peaks in the spectra of eight other dipeptides could be readily explained; this suggests that a significant number of dipeptides follow the same general fragmentation mechanisms. PMID- 24234643 TI - Identification of deoxynucleoside-polyaromatic hydrocarbon adducts by capillary zone electrophoresis-Continuous Flow-fast atom bombardment mass spectrometry. AB - Capillary zone electrophoresis coupled to continuous flow-fast atom bombardment mass spectrometry is shown to have utility for the detection and characterization of adducts formed by the covalent attachment of four polyaromatic hydrocarbon (PAH) and amino-PAH compounds to deoxyguanosine. Normal scanning provided structural information for a 1.3 ng injection of a model adduct, while 1.3 ng of each of a mixture of adducts was sufficient to determine their molecular weights by monitoring the constant neutral loss of deoxyribose. Exploitation of this loss in the multiple reaction monitoring mode resulted in the detection of low picogram amounts of target adducts in mixtures. PMID- 24234644 TI - Novel 3-hydroxylated leukotriene b4 metabolites from ethanol-treated rat hepatocytes. AB - Coincubations of radiolabeled leukotriene B4 (LTB4) and ethanol with isolated rat hepatocytes led to formation of one dihydroxylated and two novel beta-oxidized metabolites of LTB4. The major radioactive peaks from reverse-phase-high performance liquid chromatography (RP-HPLC) eluted with material absorbing UV light maximally at 270 nm, with shoulders at 260 and 280 nm, indicating retention of the conjugated triene structure of the parent molecule in each metabolite structure. Following purification, catalytic reduction, and derivatization, mass spectrometric analysis revealed that all three metabolites were hydroxylated at the C-3 carbon atom based on characteristic ions at m/z 201 and 175 in the electron ionization mass spectra of the metabolites. Negative-ion electron capture mass spectrometry of the metabolites as pentafluorobenzyl (PFB) ester, trimethylsilyl ether derivatives aided structural characterizations while revealing interesting fragmentations. A ketene-containing ion appeared to result from the loss of both PFB groups (one as PFB alcohol), while a lactone alkoxide ion appeared to result following loss of PFB and bis (trimethylsilyl) ether. From these data three novel LTB4 metabolites were suggested to be 3,20-dihydroxy-LTB4 (3,20-diOH-LTB4), 3-hydroxy-18-carboxy-LTB4 (3-OH-18-COOH-LTB4), and 3-hydroxy-16 carboxy-LTB3 (3-OH-16-COOH-LTB3). The significance of the almost exclusive formation of these 3-hydroxylated LTB4 metabolites in the presence of ethanol is currently unknown, but may result from interrupted beta-oxidation from the C-1 carboxyl moiety. PMID- 24234646 TI - Implication of the charge site in "charge-remote" fragmentations. PMID- 24234645 TI - Charge-remote fragmentation during FAB-CAD-B/E linked-scan mass spectrometry of aminoethyl-triphenylphosphonium derivatives of fatty acids. AB - The carboxyl group of fatty acids is derivatized by aminoethyl triphenylphosphonium (AETPP) bromide. Fast atom bombardment (FAB) collision activated dissociation (CAD) B/E linked-scan mass spectrometry of these fixed charge derivatives shows typical charge-remote fragmentation (CRF). Locations of various structural modifications in fatty acids can be recognized easily from CAD spectra of the AETPP derivatives. Because the triphenylphosphonium group localizes positive charge in the molecule, and because a key requirement for CRF is a tightly localized charge site, these preionized molecules fragment under FAB CAD conditions more effectively than other derivatives that involve ionic bonding with metal cations or protonation of basic sites. Thus, CAD of AETPP derivatives is likely to produce more structurally informative spectra and provide an opportunity to gain additional under-standing of the CRF process. The most profound difference between the AETPP derivatives and other cations in positive mode FAB-CAD-B/E-MS is reflected in the substantial improvement of detection limits for the AETPP derivatives over those for the metal cation adducts. For several fatty acids (C10-C22) tested, the detectability can be enhanced by one to two orders of magnitude when the analysis is performed on the AETPP derivative. In addition, for the analysis of fatty acid mixtures, the FAB mass spectrum of AETPP derivatives produces a relative intensity of the molecular ion peak for each component of the mixture that more closely represents its mole fraction than does that of metal ion adducts. PMID- 24234650 TI - Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia. AB - Familial hypercholesterolaemia (FH) is characterized by increased circulating low density lipoprotein (LDL) cholesterol leading to premature atherosclerosis and coronary heart disease. Although FH is usually caused by mutations in LDLR, mutations in APOB and PCSK9 also cause FH but only a few mutations have been reported, APOB p.R3527Q being the most common. However, 30-80% of clinical FH patients do not present an identifiable mutation in any of the described genes. To identify the genetic cause of the hypercholesterolaemia in 65 patients without mutations in LDLR, PCSK9 or in fragments of exon 26 and 29 of APOB currently analysed, we performed whole sequencing of APOB by pyrosequencing. A total of 10 putative mutations in APOB were identified. Flow cytometry with fluorescently labelled LDL from patients and relatives showed that p.Arg1164Thr (exon 22) and p.Gln4494del (exon 29) presented a 40% decrease in internalization in lymphocytes and HepG2 cells, very similar to APOB3527. The proliferation assays with U937 cells showed reduced growth for both cases. The variant p.Tyr1247Cys was found to be neutral and other three alterations were considered polymorphisms. Our results emphasize the need to study the whole APOB in routine protocols to improve patient identification and cardiovascular risk assessment. PMID- 24234649 TI - Dystrophic muscle improvement in zebrafish via increased heme oxygenase signaling. AB - Duchenne muscular dystrophy (DMD) is caused by a lack of the dystrophin protein and has no effective treatment at present. Zebrafish provide a powerful in vivo tool for high-throughput therapeutic drug screening for the improvement of muscle phenotypes caused by dystrophin deficiency. Using the dystrophin-deficient zebrafish, sapje, we have screened a total of 2640 compounds with known modes of action from three drug libraries to identify modulators of the disease progression. Six compounds that target heme oxygenase signaling were found to rescue the abnormal muscle phenotype in sapje and sapje-like, while upregulating the inducible heme oxygenase 1 (Hmox1) at the protein level. Direct Hmox1 overexpression by injection of zebrafish Hmox1 mRNA into fertilized eggs was found to be sufficient for a dystrophin-independent restoration of normal muscle via an upregulation of cGMP levels. In addition, treatment of mdx(5cv) mice with the PDE5 inhibitor, sildenafil, which was one of the six drugs impacting the Hmox1 pathway in zebrafish, significantly increased the expression of Hmox1 protein, thus making Hmox1 a novel target for the improvement of dystrophic symptoms. These results demonstrate the translational relevance of our zebrafish model to mammalian models and support the use of zebrafish to screen for new drugs to treat human DMD. The discovery of a small molecule and a specific therapeutic pathway that might mitigate DMD disease progression could lead to significant clinical implications. PMID- 24234648 TI - No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis. AB - Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS. PMID- 24234651 TI - Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes. AB - In the human, mutations of OTX2 (Orthodenticle homeobox 2 transcription factor) translate into eye malformations of variable expressivity (even between the two eyes of the same individual) and incomplete penetrance, suggesting the existence of subtle thresholds in OTX2 activity. We have addressed this issue by analyzing retinal structure and function in six mutant mice with graded Otx2 activity: Otx2(+/+), Otx2(+/AA), Otx2(+/GFP), Otx2(AA/AA), Otx2(AA/GFP) and Otx2(GFP/GFP). Null mice (Otx2(GFP/GFP)) fail to develop the head and are embryonic lethal, and compound heterozygous Otx2(AA/GFP) mice show a truncated head and die at birth. All other genotypes develop until adulthood. We analyzed eye structure and visual physiology in the genotypes that develop until adulthood and report that phenotype severity parallels Otx2 activity. Otx2(+/AA) are only mildly affected whereas Otx2(+/GFP) are more affected than Otx2(+/AA) but less than Otx2(AA/AA) mice. Otx2(AA/AA) mice later manifest the most severe defects, with variable expressivity. Electrophysiological and histological analyses of the mouse retina revealed progressive death of bipolar cells and cone photoreceptors that is both Otx2 activity- and age-dependent with the same ranking of phenotypic severity. This study demonstrates the importance of gene dosage in the development of age dependent pathologies and underscores the fact that small gene dosage differences can cause significant pathological states. PMID- 24234652 TI - LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. AB - Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also functions as an inhibitor of Wnt/beta-catenin signaling. The identified mutations in LRP4 are located at the edge of its 3rd beta-propeller domain and decrease binding affinity of LRP4 for both MuSK and agrin. Mutations in the LRP4 3rd beta-propeller domain were previously reported to impair Wnt signaling and cause bone diseases including Cenani-Lenz syndactyly syndrome and sclerosteosis-2. By analyzing naturally occurring and artificially introduced mutations in the LRP4 3rd beta-propeller domain, we show that the edge of the domain regulates the MuSK signaling whereas its central cavity governs Wnt signaling. We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position specific manner. PMID- 24234653 TI - Functional microRNAs and target sites are created by lineage-specific transposition. AB - Transposable elements (TEs) account for nearly one-half of the sequence content in the human genome, and de novo germline transposition into regulatory or coding sequences of protein-coding genes can cause heritable disorders. TEs are prevalent in and around protein-coding genes, providing an opportunity to impart regulation. Computational studies reveal that microRNA (miRNA) genes and miRNA target sites reside within TE sequences, but there is little experimental evidence supporting a role for TEs in the birth of miRNAs, or as platform for gene regulation by miRNAs. In this work, we validate miRNAs and target sites derived from TE families prevalent in the human genome, including the ancient long interspersed nuclear element 2 (LINE2/L2), mammalian-wide interspersed repeat (MIR) retrotransposons and the primate-specific Alu family. We show that genes with 3' untranslated region (3' UTR) MIR elements are enriched for let-7 targets and that these sites are conserved and responsive to let-7 expression. We also demonstrate that 3' UTR-embedded Alus are a source of miR-24 and miR-122 target sites and that a subset of active genomic Alus provide for de novo target site creation. Finally, we report that although the creation of miRNA genes by Alu elements is relatively uncommon relative to their overall genomic abundance, Alu-derived miR-1285-1 is efficiently processed from its genomic locus and regulates genes with target sites contained within homologous elements. Taken together, our data provide additional evidence for TEs as a source for miRNAs and miRNA target sites, with instances of conservation through the course of mammalian evolution. PMID- 24234654 TI - alpha-Actinin-3 deficiency alters muscle adaptation in response to denervation and immobilization. AB - Homozygosity for a common null polymorphism (R577X) in the ACTN3 gene results in the absence of the fast fibre-specific protein, alpha-actinin-3 in ~16% of humans worldwide. alpha-Actinin-3 deficiency is detrimental to optimal sprint performance and benefits endurance performance in elite athletes. In the general population, alpha-actinin-3 deficiency is associated with reduced muscle mass, strength and fast muscle fibre area, and poorer muscle function with age. The Actn3 knock-out (KO) mouse model mimics the human phenotype, with fast fibres showing a shift towards slow/oxidative metabolism without a change in myosin heavy chain (MyHC) isoform. We have recently shown that these changes are attributable to increased activity of the calcineurin-dependent signalling pathway in alpha-actinin-3 deficient muscle, resulting in enhanced response to exercise training. This led us to hypothesize that the Actn3 genotype influences muscle adaptation to disuse, irrespective of neural innervation. Separate cohorts of KO and wild-type mice underwent 2 weeks immobilization and 2 and 8 weeks of denervation. Absence of alpha-actinin-3 resulted in reduced atrophic response and altered adaptation to disuse, as measured by a change in MyHC isoform. KO mice had a lower threshold to switch from the predominantly fast to a slower muscle phenotype (in response to immobilization) and a higher threshold to switch to a faster muscle phenotype (in response to denervation). We propose that this change is mediated through baseline alterations in the calcineurin signalling pathway of Actn3 KO muscle. Our findings have important implications for understanding individual responses to muscle disuse/disease and training in the general population. PMID- 24234655 TI - The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice. AB - Mutations in fukutin-related protein (FKRP) underlie a group of muscular dystrophies associated with the hypoglycosylation of alpha-dystroglycan (alpha DG), a proportion of which show central nervous system involvement. Our original FKRP knock-down mouse (FKRP(KD)) replicated many of the characteristics seen in patients at the severe end of the dystroglycanopathy spectrum but died perinatally precluding its full phenotyping and use in testing potential therapies. We have now overcome this by crossing FKRP(KD) mice with those expressing Cre recombinase under the Sox1 promoter. Owing to our original targeting strategy, this has resulted in the restoration of Fkrp levels in the central nervous system but not the muscle, thereby generating a new model (FKRP(MD)) which develops a progressive muscular dystrophy resembling what is observed in limb girdle muscular dystrophy. Like-acetylglucosaminyltransferase (LARGE) is a bifunctional glycosyltransferase previously shown to hyperglycosylate alpha-DG. To investigate the therapeutic potential of LARGE up regulation, we have now crossed the FKRP(MD) line with one overexpressing LARGE and show that, contrary to expectation, this results in a worsening of the muscle pathology implying that any future strategies based upon LARGE up-regulation require careful management. PMID- 24234656 TI - West Nile Virus Infection in the Immunocompromised Patient. AB - West Nile virus infection has become the predominant cause of flavivirus associated encephalitis in the US. While 80 % of infected individuals are asymptomatic, 20 % develop symptoms including fever, headache, transient rash and gastrointestinal symptoms. Among the immunocompetent population, 1 in 150 develop neuroinvasive disease characterized by acute flaccid paralysis, Parkinsonian cogwheel rigidity, meningitis, encephalitis, meningoencephalitis and asymmetric muscle weakness (Mostashari et al. in Lancet 358:261-264, 2001). In the immunocompromised population such as transplant recipients and HIV-infected and chemotherapy patients, the incidence of neuroinvasive disease may be increased. The largest population studied is recipients of solid organ transplants, with data on both donor-derived and naturally occurring transmissions. The risk of neuroinvasive disease in donor-derived infection is estimated to be between 50 % and 75 % while in those with mosquito-borne transmission the risk is estimated at 40 % of those infected (Kumar et al. in Am J Transplant 4:1883-1888, 2004). With significant morbidity associated with donor transmission, specific pretransplant screening recommendations are reviewed. Treatment includes supportive care and consideration for the use of intravenous immunoglobulin. PMID- 24234659 TI - The effect of lumbar support belts on isometric force production during a simulated lift. AB - The use of back support belts by industrial workers has become common in recent years. The rationale for the use of these belts is based on the theory that they increase intra-abdominal pressure. Raised intra-abdominal pressure is believed to reduce compression forces on the spinal column and to assist the back extensor muscles in producing extension torque. The assistance of the belt is believed to protect the spine from injury. Thirty males and thirty females participated in this study which assessed the effect of two different back support belts (one synthetic and one leather) on isometric muscle-force production of individuals performing a static leg lift (SLL). A Latin Square double cross-over design was employed. Analysis of variance tests revealed that in males the use of the synthetic belt allowed for greater force production than a control trial, but no difference could be detected between the leather belt and either the synthetic belt or the control. In the female group, no difference in force production occurred across the three conditions. Implications and suggestions for further study are discussed. PMID- 24234660 TI - Effects of work and rest on upper extremity signs and symptoms of workers performing repetitive tasks. AB - The temporal relationship between work and signs and symptoms of upper extremity musculoskeletal disorders among workers at risk is relatively unexplored. The study focused on changes in upper extremity circumference, volume, sensory threshold, and reported symptoms after work and rest. All workers (N=50) performed a repetitive poultry processing task and had exhibited upper extremity signs and symptoms in baseline testing prior to this study. These workers manifested significantly increased upper extremity circumference following a period of rest, with circumferences decreasing during work. Upper extremity volume and reported swelling also decreased during work. Reports of tenderness were significantly greater after work than after rest, while reports of pain were greatest after a short rest interval. Results show that the signs and symptoms observed in these workers were manifestations of occupational cumulative trauma and that further study of the relationship between work and signs and symptoms is needed. PMID- 24234661 TI - The effect of workplace based strengthening on low back injury rates: A case study in the strip mining industry. AB - The purpose of this study was to demonstrate the effect of a once a week exercise program focused specially at lumbar extensor strengthening. This is a comparative study where workers volunteered to exercise were compared to workers who did not exercise. Low back claims for one year were noted to document efficacy of the training program. Change in strength was also noted. There was a 54% to 104% increase in strength during a 20 week program. The incidence of back injuries in the exercise group was 52 injuries per 200,000 employee hours versus the industry average of 1.09 back injuries per 200,000 employee hours. The average incidence of injury for the previous nine years at the company participating in the program was 2.94 injuries per 200,000 employee hours. The injury incidence in the workers not exercising was 2.55 injuries for 200,000 employee hours. The average workers' compensation liability dropped from $14, 430.00 per month to $380.00 per month for the study year. The significant increase in strength associated with the exercise program correlated with the greatly reduced incidence of back claims. PMID- 24234657 TI - Animal migraine models for drug development: status and future perspectives. AB - Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related responses are likely to be behavioral, allowing multiple experiments in each individual animal. Distinction is made between acute and prophylactic models and how to validate each of them. Modern insight into neurobiological mechanisms of migraine is so good that it is only a question of resources and efforts that determine when valid models with ability to predict efficacy in migraine will be available. PMID- 24234662 TI - Database analysis of injury patterns in an institution for developmental disabilities. AB - This paper reports the results of a statistical analysis of injuries to the clients and the employees of a state facility for people with developmental disabilities, as recorded in the respective databases of the institution. The goal of the analysis was to identify the characteristics and patterns of injuries in order to identify priorities for technological intervention. Databases for 2000 client injuries and for 900 direct care staff injuries between 1988 and 1991 were analyzed retrospectively. Most of the injuries were sustained by the direct care staff and involved their backs. The injuries occurred in the institution's bedrooms (approximately 25%) and bathrooms (approximately 15%) and took place mainly during the early morning (approximately 30%) and evening rush (20%). The time of day and location of the injuries of clients coincided with those of the injuries of employees. These findings direct the focus of technological based interventions. PMID- 24234663 TI - The potential impact of the Workers' Compensation System on quality of life outcomes: A clinical analysis. AB - It is widely recognized that the Workers' Compensation System has evolved into a costly adversarial, stress engendering set of interactions. Most prior research has examined the pathology of the individual which contributes to these costs. This paper presents an analysis of the ways that the system itself is pathogenic. Based on a model of factors comprising health-related quality of life, we analyze how the environment of the Workers' Compensation System promotes increased symptom reports, decreased functional status and negative general health perceptions while fostering destructive anxieties. We recommend that future prospective research move from a focus on the individual to a focus on the system and its interaction with the individual. PMID- 24234664 TI - Guidelines for the identification of barriers to rehabilitation of back injuries. AB - Not all patients with back pain recover within the expected natural recovery period. Addressing only the physical component and ignoring the psychosocial may lead to treatment failure. Recognition of typical circumstances that may become barriers to rehabilitation enhances the recovery process. Barriers to rehabilitation and questions to help determine their existence are discussed. Asking pertinent questions enables clinicians to identify those who may need redirection. This re-direction may reduce treatment time, resulting in cost savings for the third party payer and a reduction in health care dollars spent on rehabilitation. Most importantly, resolution of possible barriers and rapid recovery allows the patient to return to a normal lifestyle. PMID- 24234665 TI - Active metabolism in larval and juvenile fish: ontogenetic changes, effect of water temperature and fasting. AB - Oxygen consumption, ammonia excretion and fish swimming speed were measured in fish induced to swim by optomotor reaction in a circular metabolism chamber. The relationship between the swimming speed and fish metabolism described by exponential equations allowed the extrapolation to the standard metabolism, i.e. at zero swimming speed. The partitioning of the catabolised protein in the energy supply was estimated based on AQ (volume of ammonia/ volume of oxygen) values. Weight specific standard metabolism, as expressed by the ammonia excretion rate, decreased by one order of magnitude in coregonids as the fish grew from 20 to 780 mg body weight. The slope of the relationship between oxygen uptake and swimming speed decreased in coregonid ontogenesis. In salmon, after 12 days of fasting 28% of energy used was derived from protein, whilst coregonid juveniles utilized mostly lipid. Active swimming in fasted juveniles of coregonid, as well as in salmon, led to the accelerated utilization of protein as a source of energy, based on AQ coefficients. In juveniles acclimated to a range of water temperatures from 14 to 26 degrees C, the changes in standard or active metabolic rate (expressed as oxygen uptake or ammonia excretion) were described by Q10 coefficients. They were generally higher for the ammonia excretion rate than for the oxygen uptake rate and for active metabolism than for standard metabolism. Utilization of protein as energy for swimming differed significantly between the species, being in general one order of magnitude higher in coregonids than in salmon. The use of protein for swimming activity tended to decrease during coregonid ontogenesis. PMID- 24234666 TI - The effect of 3,3',5-triiodo-L-thyronine and 17-alpha-methyltestosterone on growth and body composition of the glass stage of the eel (Anguilla anguilla L). AB - This study was undertaken to determine the influence of orally administered 3,3',5-triiodo-L-thyronine (T3) or 17-alpha-methyltestosterone (MT) on growth and body composition of the eel (Anguilla anguilla L.) during the glass stage.Elvers receiving 20 or 40 ppm of T3 in the food weighed significantly more (P < 0.05) than controls. However, after 61 days of treatment a dosage of 60 ppm was not efficacious.Terminal percentages of body protein were significantly lower (P < 0.05) in elvers that received 20 ppm or 40 ppm T3 in their diets, than in the control. Crude body fat content was higher (P < 0.05) in elvers receiving 20 ppm (29% fat) or 40 ppm (28% fat), than in the controls (26% fat). Compared to the control, diets containing T3 at 20 or 40 ppm increased the body glucose concentration.Glass eels fed a diet containing 1 or 10 ppm MT grew significantly more slowly (P < 0.05) than the controls.Total body protein content was higher (P < 0.05), but total body crude fat content was lower (P < 0.05) in elvers fed a diet with 1 or 10 ppm MT compared to the controls. Total body glucose concentration of elvers administered 10 ppm MT was significantly lower (P < 0.05) than that of the control groups. PMID- 24234667 TI - Ultrastructural changes in the parrotfish thyroid afterin vitro stimulation with bovine thyrotropin. AB - Six groups of thyroid glands ofScarus dubius were examined and compared by electron microscopy after anin vitro culture for 4h with graded doses of bovine thyrotropin (bTSH). Five doses of bTSH were used encompassing the full range of the dose-response curve developed for this tissue. Upon electron microscopic examination, micrographs were taken randomly and at the same magnification, and three intracellular inclusions were quantified. The relative surface density of rough endoplasmic reticulum (rER) and the relative surface area of lysosomes and engulfed colloid droplets were recorded for each group. Three treatment groups, (1) control, no bTSH, (2) tissues exposed to 1 mIU/ml bTSH, and (3) tissues exposed to 2 mIU/ml bTSH, did not differ from each other in the quantified organelles nor in general appearance. Overall, these three groups were similar in appearance to the ultrastructure described in other teleosts except for a lack of flagellated cells. Compared to the first three groups, treatment with 5 mIU/ml bTSH, increased the density of rER, and the proportion of cell area occupied by lysosomes and engulfed colloid. This group also possessed either more microvilli or pseudopods at the lumenal surface of the follicular epithelium. After exposure to 10 mIU/ml bTSH there was an even greater increase in surface density of rER, and in surface area occupied by lysosomes and engulfed colloid droplets. The apical portion of this group was highly irregular, commonly displaying pseudopods. Group (6), (20 mIU/ml), showed a decline in cytoplasm in comparison to group (5) with many epithelial cells breaking apart. A few cells in this group were still intact but contained huge engulfed colloid droplets which extended from the basal to apical borders. This first detailed description suggests that the teleost thyroid gland undergoes ultrastructural changes with exogenous TSH stimulation in a manner similar to that seen in higher vertebrates. PMID- 24234668 TI - Effects of (D-Ala(6), Pro (9)N ethylamide) - LHRH on plasma levels of gonadotropin, 17alpha,20beta-dihydroxy-4-pregnen-3-one and testosterone in male goldeye (hiodon alosoides Rafineque). AB - Male goldeye were treated with (D-Ala(6), Pro(9)-N ethylamide) - LHRH (LHRH-A) in saline or a silastic pellet (100 ug.kg(-1) body weight) and changes in plasma gonadotropin (GtH), 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20betaP) and testosterone (T) levels were determined by radioimmunoassay. LHRH-A increased plasma GtH levels, with the response to LHRH-A in saline being of much greater magnitude and duration than the response to silastic pellet implants. Seasonal differences were found in the response to LHRH-A. Spermiated fish were the most responsive, recrudescing fish the least, and regressed fish displayed an intermediate response. Plasma 17alpha,20betaP levels were elevated in response to LHRHA in fish of all sexual stages although the magnitude of the increase was not related to the magnitude of the increase in GtH levels. Treatment with LHRH-A also resulted in a transitory increase in plasma T levels. The endocrine control of GtH and steroid secretion in goldeye is discussed in relation to studies in cyprinids and salmonids. PMID- 24234669 TI - A case-based approach to the development of practice-based competencies for accreditation of and training in graduate programs in genetic counseling. AB - The American Board of Genetic Counseling (ABGC) sponsored a consensus development conference with participation from directors of graduate programs in genetic counseling, board members, and expert consultants. Using a collective, narrative, and case-based approach, 27 competencies were identified as embedded in the practice of genetic counseling. These competencies were organized into four domains of skills: Communication; Critical Thinking; Interpersonal, Counseling, and Psychosocial Assessment; and Professional Ethics and Values. The adoption of a competency framework for accreditation has a variety of implications for curriculum design and implementation. We report here the process by which a set of practice-based genetic counseling competencies have been derived; and in an accompanying article, the competencies themselves are provided. We also discuss the application of the competencies to graduate program accreditation as well as some of the implications competency-based standards may have for education and the genetic counseling profession. These guidelines may also serve as a basis for the continuing education of practicing genetic counselors and a performance evaluation tool in the workplace. PMID- 24234670 TI - Practice-based competencies for accreditation of and training in graduate programs in genetic counseling. AB - In January 1996, the American Board of Genetic Counseling (ABGC) adopted 27 practice-based competencies as a standard for assessing the training of graduate students in genetic counseling. These competencies were identified and refined through a collective, narrative process that took place from January through November 1994, and included directors of graduate programs in genetic counseling, ABGC board members and expert consultants. These competencies now form the basis of the document "Requirements for Graduate Programs in Genetic Counseling Seeking Accreditation by the American Board of Genetic Counseling" (American Board of Genetic Counseling, 1996). The competencies are organized into four domains and are presented and discussed in this article. PMID- 24234671 TI - Emerging quality improvement measures in genetic counseling. AB - The need to establish guidelines for total quality management in genetic counseling is now recognized as new genetic technologies are being introduced into genetics services and primary care. Genetic counselors have an important role in developing methods for assuring quality in the genetic counseling process. Emerging quality improvement measures as well as selected examples from the Quality Assurance Program in the Genetics Services Division at the Foundation for Blood Research are presented as examples of direct genetic counselor involvement. Suggestions for future directions of quality improvement activities for genetic counselors are discussed. PMID- 24234672 TI - Folic acid and the prevention of neural tube defects: A position paper of the national society of genetic counselors. AB - Considerable scientific evidence demonstrates the reduction in risk for neural tube defects (NTDs) associated with maternal preconceptional folic acid supplementation. The National Society of Genetic Counselors (NSGC) endorses the U.S. Public Health Service recommendations for folic acid supplementation at the 0.4 mg level for women in the general population and at the 4.0 mg level for women at high or increased risk for NTD pregnancies for at least 4 weeks prior to active pursuit of conception. We encourage targeted educational efforts and surveillance to assess results of this dietary supplementation. The NSGC further urges the Food and Drug Administration to fortify staple foodstuffs with folic acid for a population-based approach to minimize the number of NTD births. PMID- 24234673 TI - Chronic exposure to bisphenol A can accelerate atherosclerosis in high-fat-fed apolipoprotein E knockout mice. AB - In epidemiological studies, there is growing concern regarding the association between human exposure to bisphenol A (BPA) and an increased risk for cardiovascular disease. Therefore, we investigated whether BPA accelerates atherosclerosis in mouse model. Apolipoprotein E knockout (ApoE(-/-)) mice were fed a high-fat and high-cholesterol diet with or without 50 MUg/kg body weight/day BPA for 12 weeks. Atherosclerotic lesions of the aorta and aortic sinus were evaluated by Oil red O staining. After the 12-week BPA treatment, BPA significantly increased atherosclerotic lesions in the aortas of ApoE(-/-) mice by 1.7-fold (p = 0.03). Non-high-density lipoprotein (HDL) cholesterol levels in the BPA group were significantly higher compared to those in the control group (1,035 +/- 70 vs. 484 +/- 48 mg/dL, p = 0.02) although body weight and blood glucose levels were not different between groups. Human umbilical vein endothelial cells (HUVECs) were treated with 0.1-10 nM BPA but BPA did not affect HUVEC proliferation or migration. BPA could accelerate atherosclerosis in ApoE(-/ ) mice, which may have resulted from an increase in non-HDL cholesterol levels. PMID- 24234674 TI - Investigation of four candidate genes (IGF2, JHDM1A, COPB1 and TEF1) for growth rate and backfat thickness traits on SSC2q in Large White pigs. AB - As important quantitative traits, the growth rate and backfat thickness are controlled by multiple genes. The aim of this investigation was to evaluate the effect of the single and multiple SNPs of four candidate genes (IGF2, JHDM1A, COPB1 and TEF-1) on growth rate and backfat thickness. The four candidate genes were mapped on the p arm of SSC 2, and there are several QTLs, such as average daily gain, backfat thickness, an imprinted QTLs affecting muscle mass and fat deposition have been reported in this region. The polymorphisms of these genes were detected using PCR-RFLP methods, mixed procedure was used to analyze the single marker association with the growth and backfat thickness traits, and the gene-gene combination was investigated using multiple-markers analysis. The single marker association analysis indicated that the IGF2 intron-3 g.3072G > A and the substitution g.93G > A of TEF-1 gene were significantly associated with the age at 100 kg (P < 0.05). The JHDM1A 3'UTR g.224C > G, the c.3096C > T polymorphism of COPB1 gene and the substitution g.93G > A of TEF-1 gene were all significantly associated with the backfat at the shoulder (P < 0.05), backfat at the last rib, backfat at the lumbar, and the average backfat thickness, respectively. The multiple-markers analysis indicated that IGF2 and TEF-1 integrated gene networks for the age at 100 kg. Therefore, we can suggest that the polymorphism of IGF2 and TEF-1 gene could be used in marker-assisted selection for the age at 100 kg in Large White pigs. PMID- 24234676 TI - Effect of augmented sensorimotor input on learning verbal and nonverbal tasks among children with autism spectrum disorders. AB - Thirty-four children, with autism spectrum disorders, ages 4-14 years, were matched and randomly assigned to one of two conditions for learning a novel juice making task and producing two novel words about the event. Seventeen sighted children were manually guided to perform the task and tactually prompted during imitated productions of novel words for the event. Their matched controls heard the novel words and watched the juice-making task being performed. Performances on four verbal and two nonverbal measures right after instruction and at 24-48 h post-instruction, revealed higher scores for the ''hands-on'', participation than observation group on both verbal and nonverbal tasks. This study offers a paradigm for exploring the instructional advantage of enhanced participatory experience. PMID- 24234675 TI - Restricted and repetitive behaviors in autism spectrum disorders and typical development: cross-sectional and longitudinal comparisons. AB - Restricted and repetitive behaviors (RRBs) are characteristic of autism spectrum disorders (ASD). However, compared to social and communicative impairments, less is known about their development, trajectory and etiology. This study explored RRBs in young children with ASD matched to typically developing (TD) children on non-verbal development. RRBs were coded from direct observation at three time points within 13 months of development. Children with ASD displayed higher frequency and greater diversity of RRBs at all time points, however RRBs were not unique to ASD and evident in the TD control group albeit at a reduced frequency. RRBs did not correlate with social and communicative impairments in the ASD group, suggesting dissociation between these domains. PMID- 24234677 TI - Using the circumplex model of affect to study valence and arousal ratings of emotional faces by children and adults with autism spectrum disorders. AB - The affective circumplex model holds that emotions can be described as linear combinations of two underlying, independent neurophysiological systems (arousal, valence). Given research suggesting individuals with autism spectrum disorders (ASD) have difficulty processing emotions, we used the circumplex model to compare how individuals with ASD and typically-developing (TD) individuals respond to facial emotions. Participants (51 ASD, 80 TD) rated facial expressions along arousal and valence dimensions; we fitted closed, smooth, 2-dimensional curves to their ratings to examine overall circumplex contours. We modeled individual and group influences on parameters describing curve contours to identify differences in dimensional effects across groups. Significant main effects of diagnosis indicated the ASD-group's ratings were constricted for the entire circumplex, suggesting range constriction across all emotions. Findings did not change when covarying for overall intelligence. PMID- 24234678 TI - Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype. AB - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow limitation. Given that multiple systems other than the lung can be impaired in COPD patients, the traditional FEV1/FVC ratio shows many limitations in COPD diagnosis and assessment. Certain heterogeneities are found in terms of clinical manifestations, physiology, imaging findings, and inflammatory reactions in COPD patients; thus, phenotyping can provide effective information for the prognosis and treatment. However, phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD, and the role of phenotypes in COPD prevention and early diagnosis remains unclear. This shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain genes. This review briefly describes the heterogeneity of COPD, with focus on recent advances in the correlations between genotypes and phenotypes. The potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated. PMID- 24234679 TI - Monocyte subsets and their differentiation tendency after burn injury. AB - Monocytes are critical effectors and regulators of immune response. Studying the nomenclature of monocyte subsets may be beneficial for understanding the complex function of monocytes in steady and inflammatory states. A monocyte has the potential to differentiate into dendritic cells or macrophages, and this behavior significantly changes in severely burned patients and mice. The findings in the present study may help enhance understanding on the perturbation of the immune system after severe burn injury. PMID- 24234681 TI - Hydrocele of the canal of Nuck--an old problem revisited. AB - Herein the authors describe the case of a young woman presenting with a tender lump in her groin. Clinically the differential was of either a reactive lymph node or a femoral hernia. Ultrasound scan was urgently arranged and showed a cystic lesion. Surgical exploration was carried out and revealed this to be a hydrocele of the canal of Nuck. This was excised and the patient's symptoms resolved and she was discharged home the following day. We explore the embryology, pathophysiology and management of this rare entity. PMID- 24234680 TI - Sufficient downward rotation of the christa philtri on the cleft side: a modified technique. AB - Cleft lip and palate (CLP) is the most common craniofacial congenital deformity. The etiology of CLP is multifactorial and involves complex interactions between environmental and genetic factors. Millard's rotation advancement technique has long been considered as state-of-the-art for unilateral cleft lip repair. However, this method may leave the christa philtri on the cleft side insufficiently downward rotated, especially in wide complete clefts. In this study, we introduce a modified technique to better rotate the christa philtri on the cleft side down. The skin, muscle, and mucosa in the deformed region were dissected and separately maneuvered. Sixty patients with unilateral complete cleft lip and palate were operated with this technique. The lip height, lip length, and relative height of the christa philtri were measured for symmetry evaluation. No significant difference was observed between the relative height of the christa philtri on both sides, either immediate (P = 0.214) or 10 months after surgery (P = 0.344). The difference observed in the lip height and lip length immediately after surgery became statistically insignificant after 10 months (P = 0.104 for lip height and 0.121 for lip length). These results suggested that sufficient and stable downward rotation of the christa philtri on the cleft side can be achieved using our technique. PMID- 24234683 TI - From hazard assessment to life cycle assessment : The birth of a new Journal. PMID- 24234682 TI - The impact of hypoxia in hepatocellular carcinoma metastasis. AB - Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondary growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis. PMID- 24234684 TI - Bioaccumulation of selected organochlorines in bats and tits: Influence of chemistry and biology. AB - We analyzed six organochlorine compounds (HCB, lindane, p,p'-DDE, PCB # 138, #153, and # 180) from populations of the European great tit (Parus major) and from five species of bats (Pipistrellus pipistrellus, Nyctalus noctula, Plecotus auritus, Plecotus austriacus, Myotis myotis). A weak positive correlation between Kow (n-octanol /water partition coefficient) and bioaccumulation (measured as residue values) was found within each species. However, the ratio of the concentrations in bats compared to titmice increased significantly with increasing Kow. We argue that this is explained by the intensive juvenile feeding through long-term lactation and thus by the more intensive transfer of strongly lipophilic xenobiotics from mother to juvenile in mammals compared to birds. Further, there were clear variations between bat species with ranges of up to 11 times the lowest value for a single compound. These differences are related to different feeding habits of the adults and to different species-specific life history traits, such as age at maturity and number of offspring. PMID- 24234685 TI - Measures minimise oil risk to North Wales coast. PMID- 24234686 TI - Reactions of cloned poplars to air pollution : Ozone-induced increase of stress ethylene and possible antisenescence strategies. AB - Ozone-induced changes in ethylene production, ACC oxidase activity and the contents of ACC, MACC and free PAs were studied inPopulus nigra L. cv. Loenen with high ozone sensitivity as judged by the degree of chlorophyll degradation and premature leaf abscission.Ethylene production, ACC oxidase activity, ACC content and MACC levels were induced by the one-, two-, and three-week ozone exposure (36+/-9 ppb O3 for 11 hours a day). In addition, increases in PA levels, especially in spermidine, were measured in ozone treated plants.The role of free PAs and MACC synthesis as possible antisenescence reactions is discussed. PMID- 24234687 TI - Third thematic conference on remote sensing for marine and coastal environments. PMID- 24234688 TI - N-nitrosodimethylamine in drinking water using a rapid, solid-phase extraction method. AB - A simple, rapid method for the extraction of N-nitrosodimethylamine (NDMA) from drinking and surface waters was developed using Ambersorb 572. Development of an alternative method to classical liquid-liquid extraction techniques was necessary to handle the workload presented by implementation of a provincial guideline of 9 ppt for drinking water and a regulatory level of 200 ppt for effluents. A granular adsorbent, Ambersorb 572, was used to extract the NDMA from the water in the sample bottle. The NDMA was extracted from the Ambersorb 572 with dichloromethane in the autosampler vial. Method characteristics include a precision of 4 % for replicate analyses, an accuracy of 6 % at 10 ppt and a detection limit of 1.0 ppt NDMA in water. Comparative data between the Ambersorb 572 method and liquid-liquid extraction showed excellent agreement (average difference of 12 %). With the Ambersorb 572 method, dichloromethane use has been reduced by a factor of 1,000 and productivity has been increased by a factor of 3 4. Monitoring of a drinking water supply showed rapidly changing concentrations of NDMA from day to day. PMID- 24234689 TI - Inhibition of ethoxyresorufin-O-deethylase (EROD) activity in mixtures of 2,3,7,8 tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls : EROD acitivity as biomarker in TCDD and PCB risk assessment. AB - Induction of ethoxyresorufin-O-deethylase (EROD) activity and porphyrin accumulation shows different structure-activity relationships for different polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Interactions between the two responses can strongly influence the induction and activity of EROD. The results support the conclusion that there are nonadditive interactions between nondioxin-like PCBs and dioxin-like compounds. The interaction between EROD activity and the porphyrin biosynthesis makes the prerequisite of additivity in the toxic equivalency factor concept for environmental mixtures highly spurious. Inhibition of EROD activity caused by non dioxin like compounds could have a significant impact on the value of EROD activity as a biomarker in the present methods of risk assessment for these compounds. PMID- 24234690 TI - Harmonization of methods for impact assessment. AB - Some aspects of a number of different techniques for environmental decision support, in particular risk assessment (RA) and life-cycle assessment (LCA), are briefly discussed. The importance of a coherent framework, the use of common data sets, and harmonization of methods is emphasized. The latter leads to a discussion of a fundamental difference between techniques that assess continuous emission fluxes, like RA, and techniques that assess discrete emission pulses, like LCA. The question whether it is possible to apply the same types of impact assessment models is positively answered for most models. The implications are threefold: It is allowed to employ the much easier steady-state models in pulse oriented techniques, there exist often postulated but not yet rigidly proven equivalency factors for use in e.g. life-cycle assessment, and it is possible to harmonize the models as used in pulse-oriented and in flux-oriented models. PMID- 24234691 TI - Estimation of mercury content in tailings of the gold mine area of Pocone, Mato Grosso, Brazil. AB - As in many other parts of the world, gold is produced in the surface mining region of Pocone, Mato Grosso, Brazil, using mercury. The goal of this investigation was to estimate the amount of mercury in certain tailings and to determine the area of the land that has been contaminated by the gold mining operations. Mercury concentrations from 2 to 495 ng/g (dw) were determined in the tailing materials. It was observed that only isolated sites were acting as central points of contamination. Using digital Landsat satellite data (The-matic Mapper) and aerial photos, the sites degraded by the mining were classified, and their total area was estimated to be 12.3 km(2) in the region of Pocone. It was estimated, that 4.9 km(2) were occupied by the contaminated tailings. The mean height of the pile slags was determined to be 4.5 m. From the experimentally calculated average density of the material in the tailings, 2.01 g/cm(3), the total mercury content in the piles of tailings was estimated to be 1600 +/- 350 kg. PMID- 24234692 TI - COS, CS2 and SO 2 in aluminium smelter exhaust : The contribution of aluminium production to the global COS budget. AB - Measurements of carbonyl sulfide (COS) and carbondisulfide (CS2) were carried out on samples drawn from a smoke stack of an aluminium smelter. Volume mixing ratios of 6 ppm COS and 0.1 ppm CS2 were measured for gases from the electrolysis unit that had previously passed an Al2O3 fluid bed reactor and electrostatic precipitators. Specific emissions of 1.6 kg COS and 0.03 kg CS2 per ton of primary aluminium were found. Extrapolating from this particular smelter's conditions to a world mix specific COS emissions of about 4 kg/t(Al) are calculated resulting in emissions of annually 0.08 Tg COS into the atmosphere due to electrolytic aluminium production in 1995. Besides the photochemical conversion of anthropogenic CS2 aluminium production is established to be the second major industrial source of COS probably exceeding automotive tire wear's and coal combustion's contributions. PMID- 24234693 TI - UDS-test with freon 11 (R-11). AB - Trichlorofluoromethane, in concentrations of 80, 400, 2 000, 10 000 and 50 000 ppm, was administered to rats of both sexes (Sprague Dawley) by inhalation exposure.2 000 ppm in air (= 11 200 mg/m(3)) amount to twice the MAK value of 1 000 ppm. At exposure times of 4 hours this corresponds to the MAK value defined for an 8 hour workday.Unscheduled DNA synthesis (UDS) was measured in single-cell suspensions of hepatocytes, pulmonary epithelial cells and lymphocytes of the spleen, respectively.In the pulmonary cells concentrations of 2 000, 10 000 and 50 000 ppm of freon 11 lead to a significantly increased mean silver grain count compared to a negative control group.In spleen and liver cells increasing concentrations of R 11 tend to increase the incorporation of thymidine into the DNA of the cells. These changes of the extent of unscheduled DNA synthesis can, however, not be statistically verified. PMID- 24234694 TI - Bioassays for soils. PMID- 24234695 TI - Preface. PMID- 24234696 TI - An object-oriented software for fate and exposure assessments. AB - The model system CemoS(1) (Chemical Exposure Model System) was developed for the exposure prediction of hazardous chemicals released to the environment. Eight different models were implemented involving chemicals fate simulation in air, water, soil and plants after continuous or single emissions from point and diffuse sources. Scenario studies are supported by a substance and an environmental data base. All input data are checked on their plausibility. Substance and environmental process estimation functions facilitate generic model calculations. CemoS is implemented in a modular structure using object-oriented programming. PMID- 24234697 TI - Using comparative ecotoxicology to develop quantitative species sensitivity relationships (QSSR). PMID- 24234698 TI - Kinetic constraints on theIn-situ remediation of soils contaminated with organic chemicals. AB - Cleanup of contaminated soils to comply with soil quality limits currently receives much interest.In-situ remediation of contaminated soils relies on the ability of the techniques employed to enhance the rate of release of contaminants from the soil-sorbed and nonaqueous phase liquid (NAPL) phases into the aqueous or gaseous phases from which they can be more readily removed and treated. Contaminant concentrations in these "environmentally mobile" forms usually decline over time so that the economic efficiency and the overall success of remediation technologies are subject to the "law of diminishing returns". In this paper we consider the "state of the art" in our understanding of NAPL dissolution and transport, desorption of soilsorbed contaminants and fluid flow in porous media. The extent to which these processes may constrain the success of bioremediation, pump-and-treat remediation and soil venting in relation to established soil quality limits is addressed. Finally, we suggest directions for future research and comment on legislative considerations. PMID- 24234700 TI - SARDINIA '95 - Fifth International Landfill Symposium : S. Margherita di Pula, Italy, October 2-6, 1995. PMID- 24234701 TI - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of underivatized and permethylated gangliosides. AB - Underivatized and permethylated gangliosides have been studied by the matrix assisted laser desorption (MALO) ionization technique. The samples investigated included commercially available and highly purified gangliosides from the human brain containing up to five sialic acid residues. Several permethylated gangliosides have also been studied, and MALD has proven successful in analyzing multicomponent mixtures of glycolipids with different fatty acyl residues. During the studies a variety of matrix and wavelength combinations have been tested in both the positive and negative ion modes. The best results have been obtained with the matrices 2,5-dihyd roxybenzoic acid, 4-hydrazinobenzoic acid, 1,5 diaminonaphthalene, and 6-aza-2-thiothymine. Negative ion mass spectra of the underivatized gangliosides have always been of better quality than the positive ion mass spectra; exhibiting better signal-to-noise ratio, better resolution, less fragmentation, and less adduct formation with Na(+) and K(+). With increasing number of sialic acid substituents the molecular ion region became less and less resolvable leading to broadened peaks even in the negative ion mode. Fragmentation could frequently be observed in the negative ion mode, and it was pronounced in the positive ion mode. The major fragmentation pathways corresponded to loss of sialyl groupts) and to decarboxylation of one of the sialyl residues. For underivatized gangliosides the typical sample amount used was 10-20 pmol, Permethylation led to a significant improvement in sensitivity (two orders of magnitude); the detection limit of permethylated gangliosides was about 10 fmol. The higher stability of the permethylated compounds was indicated by the fact that positive ion mass spectra exhibited only a marginal extent of fragmentation. PMID- 24234702 TI - Negative ion fast-atom bombardment tandem mass spectrometry to determine sulfate and linkage position in glycosaminoglycan-derived disaccharides. AB - Negative ion fast-atom bombardment tandem mass spectrometry has been used in the analysis of monosulfated. disaccharides. These commercially obtained disaccharides have been enzymatically prepared from glycosaminoglycans using polysaccharide lyases. Three disaccharides from chondroitin sulfate and dermatan sulfate and two disaccharides from heparan sulfate and chemically derivatized heparin were analyzed. All five disaccharides were isomeric, with differences in sulfate position and linkage position. The full-scan mass spectra are useful in differentiating isomers when the sulfate group resides on different saccharide units. This structural information was obtained from fragment ions produced through cleavage at the glycosidic linkage. The full-scan mass spectra of each monosulfated disaccharide also produced intense molecular anions having long lifetimes. Collisional activation of these resulted in tandem mass spectra rich in significant product ions. Some of these fragment ions were formed through ring cleavage and were useful in the determination of both sulfate and linkage position. PMID- 24234703 TI - The determination of glycopeptides by liquid chromatography/mass spectrometry with collision-induced dissociation. AB - Glycopeptides derived from ribonuclease B and ovomucoid have been subjected to collisioninduced dissociation (CID) in the second quadrupole of a triple quadrupole mass spectrometer. Doubly charged parent ions gave predictable fragmentation that yielded partial sequence information of the attached oligosaccharide as Hex and HexNAc units. Common oxonium ions are observed in the product ion mass spectra of the glycopeptides that correspond to HexNAc(+) (m/z 204) and HexHexNAc(+) (m/z 366). A strategy for locating the glycopeptides in the proteolytic digest mixtures of glycoproteins by ions spray liquid chromatography mass spectrometry (LC/MS) is described by utilizing CID in the declustering region of the atmospheric pressure ionization mass spectrometer to produce these characteristic oxonium ions. This LC/CID/MS approach is used to identify glycopeptides in proteolytic digest mixtures of ovomucoid, asialofetuin, and fetuin. LC/CID/MS in the selected ion monitoring mode may be used to identify putative glycopeptides from the proteolytic digest of fetuin. PMID- 24234704 TI - Fragmentation characteristic of glutathione conjugates activated by high-energy collisions. AB - Product ion spectra of fifteen monoglutathione and diglutathione conjugates have been measured using activation by 6000-eV collisions with helium in the third field-free region of a four-sector tandem mass spectrometer of EBEB configuration. Fragmentation patterns in the cation spectra have been analyzed for decompositions of the glutathione moiety that would permit recognition of an unknown as a glutathione conjugate. Five spectra from an earlier study of high energy collisional activation on a BEEB four-sector instrument have also been included in this analysis. A suite of appropriate ions was found to occur consistently,, including ions of m/z 307 comprising the glutathione tripeptide and the complementary ion [MH-307](+) or the ion radical [MH-306](+). PMID- 24234705 TI - Evidence for thermal decomposition contributions to the mass spectra of chlorinated phenoxyacid herbicides obtained by particle beam liquid chromatography mass spectrometry. AB - The spectral quality of a group of chlorinated phenoxyacid herbicides has been shown to degrade under certain conditions upon introduction into the mass spectrometer by a particle beam interface. Experiments were performed to investigate these changes in spectra. Normalized ion chromatograms were generated for the herbicides, and the results showed a broadening of the profiles of some ions, indicating a longer residence time in the ion source. These ions were postulated as coming from the ionization of thermal degradation products from the herbicides. The generation of these ions was dependent on ion source temperature, analyte concentration, and, by implication, ion source cleanliness. Tandem mass spectrometry experiments were performed on these ions from the herbicides and ions from the corresponding phenols. The tandem mass spectra of the ions from the herbicides were similar to the tandem mass spectra of the ions from the phenols. Therefore, it appears that the particle beam mass spectra of the chlorinated phenoxyacid herbicides are composite spectra with contributions from the gas phase ionization of the parent herbicides and thermal decomposition products. PMID- 24234706 TI - Importance of enhanced mass resolution in removing interferences when measuring volatile organic compounds in human blood by using purge-and-trap gas chromatography/mass spectrometry. AB - The number of volatile organic compounds (VOCs) that can be purged from human blood is so great that they cannot be separated completely by capillary gas chromatography. As a result, the single-mass chromatograms used for quantitating the target compounds by mass spectrometry have many interferences at nominal (integer) mass resolution of a quadrupole mass spectrometer. The results of these interferences range from small errors in quantitation to completely erroneous results for the target VOCs. By using a magnetic sector mass spectrometer, these interferences at nominal mass can be removed at higher resolution by lowering the ion chromatogram windows around the masses of interest. At 3000 resolution (10% valley definition), unique single-ion chromatograms can be made for the quantitation ions of the target VOCs. Full-scan mass data are required to allow the identification of unknown compounds purged from the blood. By using isotope dilution mass spectrometry, most target VOCs can be detected in the low parts per trillion range for a 10-mL quantity of blood from which the VOCs have been removed by a purge-and-trap method. PMID- 24234707 TI - Ultramark 1621 as a reference compound for positive and negative ion fast-atom bombardment high-resolution mass spectrometry. AB - Ultramark 1621, a commercially available mixture of fluorinated phosphazines, was found to be a useful calibration compound for negative and positive ion fast-atom bombardment (FAB) high-resolution mass spectrometry. Ultramark 1621 worked very well with the most widely used matrices such as glycerol, nitrobenzyl alcohol, and triethanolamine. The negative and positive ion FAB mass spectra of Ultramark include a series of intense peaks extending from 700 to 1900 u. PMID- 24234708 TI - Effect of frequency sweep direction on motion of excited ions in fourier transform ion cyclotron resonance cells. AB - Ion motion during frequency sweep excitation was computer simulated to study the effect of the direction of frequency swee on the z motion of ions in a cylindrical Fourier transform ion cyclotron resonance (T-ICR) cell. It is shown that the z motion is more forcefully excited by upsweep than by downsweep; thus at large amplitudes ions are more easily ejected to the trapping electrodes by upsweep and larger cyclotron orbits can be achieved by downsweep. This effect was confirmed by experiment and the results are favorably compared with the calculations. From these results it is concluded that downward sweeping is advantageous for ion detection and upward sweeping is preferable for ion ejection. The simulations clearly explain the effect of the direction of frequency sweep by visualizing the directions of the forces that ions experience immediately after the excitation of their cyclotron motion. It was demonstrated by experiment that the z ejection can be reduced by applying a phase-adjusted ac potential to the trapping electrodes.(847-852). PMID- 24234709 TI - Reactive collisions in quadrupole cells. 2. H/D exchange reactions of enolate ions with CH3od and C 2H 5OD. AB - The H / D exchange reactions of enolate ions with CH3OD and C2H5OD at low collision energies in the quadrupole collision cell of a hybrid tandem BEqQ mass spectrometer have been studied. The optimum parameters for exchange were elucidated using the enolate ion of acetone as a test reactant ion. With the exception of the enolate ions of 2, 4-pentanedione and dimethylmalonate, all the enolate ions studied underwent exchange with CH3OD and C2H5OD. Ion signals were observed corresponding to exchange of from one to all of the enolic hydrogen atoms. The H / D exchange reaction was more facile with C2H5OD as the reagent gas, and the results with this gas clearly permit a count of the number of enolic hydrogen atoms present in the molecule. PMID- 24234710 TI - Surface-induced dissociation of multiply protonated peptides. AB - We report here surface-induced dissociation spectra of three multiply charged peptides: doubly protonated angiotensin I, doubly protonated renin substrate, and triply protonated melittin. For comparison, the collision-activated dissociation spectra of renin substrate and melittin are also presented. The spectra show that surface-induced dissociation provides structural information on multiply charged peptides at the picomole per microliter sample concentrations compatible with electrospray ionization. For multiply protonated angiotensin I, renin substrate, and melittin, surface collisions (l00-165 eV) favor a limited number of fragmentation pathways, which are the same as those favored in collision activated dissociation experiments. PMID- 24234711 TI - Proton affinities of polyglycines assessed by using the kinetic method. AB - The proton affinities of a series of peptides, chosen to show the effects of chain length, were measured by the kinetic method using amines as standard reference bases. Proton affinities of polyglycines with residues ranging from 2 to 10 were measured and the values were found to increase as the number of residues increases. PMID- 24234714 TI - Dynamics of nonspecific adsorption of insulin to erythrocyte membranes. AB - Molecules may arrive at targets (receptors, enzymes, etc.) localized on a membrane surface by first adsorbing onto the surface and then surface diffusing to the targets. The flux rate of molecules arriving at targets via this mechanism depends on the surface diffusion coefficient of the molecules and, in some circumstances, on the adsorption/desorption kinetics. The technique of total internal reflection with fluorescence recovery after photobleaching (TIR-FRAP) was used here to study these rate parameters of fluorescein-labeled insulin (f insulin) interacting with erythrocyte ghosts. Ghosts were adhered to polylysine coated slides for TIR illumination. Some ghosts became flattened and unsealed on the polylysine so that both extracellular and cytoplasmic sides of the membrane were openly exposed to the solution. An aluminum thin film between the polylysine and the fused silica of a slide quenched 'background' fluorescence from f-insulin adsorbed directly onto the polylysine. An interference fringe pattern from two intersecting and totally internally reflecting laser beams provided surface selective excitation with a spatial variation of illumination intensity across a ghost for surface diffusion measurements. Measured characteristic values of desorption rate constants ranged from 0.043 to 270 s(-1). According to a preexisting theoretical model, the largest desorption rate constant in this range would result in some increase in the total flux rate to a perfect sink target due to capture from the surface, provided that the surface diffusion coefficient was >= about 10(-8) cm(2)/s. However, based on TIR-FRAP measurements on our system, we estimate that the surface diffusion coefficient is less than about 5*10(-10) cm(2)/s. The combination of novel techniques presented here may prove valuable to other workers seeking to make diffusive and chemical kinetic rate parameter measurements of biomolecules at biological cell membranes. PMID- 24234715 TI - Wavelength dependence of fluorescence spectra of liquid coumarin solutions. AB - The excitation wavelength dependence of steady-state fluorescence spectra of low viscosity dye solutions is reexamined. Measurements are made on some coumarins in methyl alcohol at room temperature. It is found that the fluorescence spectra depend on the excitation energy and their profile changes are due to the excitation wavelength dependence of reorientation processes in the excited state. PMID- 24234713 TI - Secondary central nervous system involvement in 599 patients with diffuse large B-cell lymphoma: are there any changes in the rituximab era? AB - The introduction of rituximab has improved the overall prognosis of diffuse large B-cell lymphoma (DLBCL). However, the impact of rituximab on central nervous system (CNS) involvement in DLBCL remains a matter of debate. Patients with DLBCL and no CNS involvement at initial diagnosis were eligible for this analysis. Patients must have received treatment either with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP). We analyzed the incidence, clinical features and outcomes of CNS involvement that developed during or after completion of therapy. A cohort of 599 patients was eligible for this analysis. With a median follow-up of 26 and 21 months, respectively, 19 of 294 (6.5 %) in the CHOP group and 13 of 305 (4.3 %) in the R CHOP group developed CNS involvement. Rituximab did not significantly reduce the risk of CNS involvement either in the univariate (P = 0.354) or in the multivariate analysis (RR 0.632, 95 % CI 0.301-1.327, P = 0.225). No patient developed CNS disease after 19 months in the R-CHOP group whereas four patients (21.1 %) in the CHOP group developed CNS disease 2 years after initial diagnosis (range 34-83 months). Systemic disease prior to or coincident with CNS occurrence was more common in the CHOP group than in the R-CHOP group (73.7 versus 38.5 %, P = 0.046). Isolated CNS events were more common in the R-CHOP group than those in the CHOP group (53.8 versus 10.5 %, P = 0.015). This study indicates that isolated CNS events are more common in DLBCL patients treated with R-CHOP than those treated with CHOP alone. Our data also suggest that the time and pattern of CNS events and systemic disease status differ with the addition of rituximab. Better methods for earlier detection and prophylaxis of CNS involvement are needed in the rituximab era. PMID- 24234716 TI - Distance distributions and dynamics of a zinc finger peptide from fluorescence resonance energy transfer measurements. AB - Time-resolved fluorescence resonance energy transfer (FRET) measurements were used to measure distance distributions and intramolecular dynamics (site-to-site diffusion) of a 28-residue single-domain zinc finger peptide in the absence and presence of zinc ion. Energy transfer was measured between TRP14 and a N-terminal DNS group. As expected, the TRP-to-DNS distance distribution for zinc-bound peptide is shorter and narrower (R av=11.2 A,hw=2.8 A) than the metal-free peptide (R av=20.1 A,hw=14.5 A). The degree of mutual donor-to-acceptor diffusion (D) was also determined for these distributions. For zinc-bound peptide there is no detectible diffusion (D<=0.2 A(2)/ns), whereas for metal-free peptide a considerable amount of motion is occurring between the donor and the acceptor (D=12 A(2)/ns). These results indicate that the zinc-bound peptide folds into a unique, well-defined conformation, whereas the metal-free conformation is flexible and rapidly changing. The absence of detectible mutual site-to-site diffusion between the donor and the acceptor in the metal-bound zinc finger peptide indicates that intramolecular motion is essentially frozen out, on the FRET time scale, as a consequence of zinc coordination. PMID- 24234717 TI - Preparation of lucifer yellow fluorescent liposomes: A method for cells' membrane labeling. AB - This report describes a method to conjugate lucifer yellow to the external surface of liposomes. The heterobifunctional cross-linking reagentN-succinimidyl 3-(2-pyridyldithio)propionate has been used to activate DMPE molecules. The DMPE dithiopyridine product has been mixed with DMPC to prepare liposome vesicles. These have been reduced by DTT and finally reacted with lucifer yellow iodoacetamide to produce the fluorescence-labeled vesicles. The quenching of their fluorescence intensity by Kl is consistent with fully exposed fluorophores. The decay of the fluorescence intensity of the lipid-bound lucifer yellow is biexponential (tau1=7.9 ns; tau2=1.1 ns), with a relative yield of 0.16. When the fluorescent liposomes are mixed with cells, the lucifer yellow-DMPE derivative is transferred. Boar spermatozoa and peripheral human blood lymphocytes have been used as cellular models. The extent of incorporation is dependent on the incubation time and temperature. At 36 degrees C, lucifer yellow fluorescence appears in the spermatozoa cells after 10 min of incubation and reaches its maximum at about 60 min. The fluorescent phospholipid derivative seems to incorporate specifically into membrane structures. The highest labeling ratio is observed with integer, scarcely motile, spermatozoa. A poorer labeling yield (~15%) is found with lymphocytes. Interestingly, photobleaching due to epiillumination of the labeled cells is apparently negligible and cells are clearly visible after irradiation times ranging from several minutes to few hours. PMID- 24234718 TI - Asymmetry of calmodulin revealed by peptide binding. AB - The binding of amphiphilic peptides to calmodulin has been studied using fluorescence energy transfer techniques. Calmodulin has no tryptophan residues but possesses two tyrosines (at positions 99 and 138) in the C-terminal half of the protein. The peptides have a single tryptophan which serves as energy acceptor for the protein tyrosine fluorescence. For the binding of mastoparan or peptide Baa17, with a tryptophan at position 3, the observed quenching of the tyrosine fluorescence of over a factor of 2 corresponds to an average tyrosine trytophan distance of less than 14 A. These results indicate that the peptides binds preferentially with the tryptophan in the C-terminal half of the protein. PMID- 24234719 TI - Effect of solvent on the cation-sensitive fluorescence of polyanions bearing 4' acryloylbenzo-18-crown-6 Units. AB - Changes in the fluorescence intensity of polyanions bearing 4'-acryloylbenzo-18 crown-6 units on the addition of cations were studied in a mixed solvent of methanol and water at 30 degrees C. The sensitivity of the change in fluorescence intensities of the polymers toward cations was strongly enhanced compared to that of the corresponding model compound. When alkali metal cations were added, the fluorescence intensity of the polymers decreased in the orders Li(+)>Na(+)>Cs(+)>Rb(+)>K(+) in a methanol-water (1?9) mixture and Li(+)>Na(+)>Rb(+)>K(+)?Cs(+) in a methanol-water (9?1) mixture. Alkaline earth metal cations and alkylamine hydrochlorides decreased the fluorescence intensity of the polymers in a methanol-water (1?9) mixture. The cation-dependent decrease in the fluorescence intensity of the polymers was affected by the water fraction in a mixed solvent of methanol and water. PMID- 24234720 TI - Brief report: Do children with autism gather information from social contexts to aid their word learning? AB - Typically developing (TD) infants could capitalize on social eye gaze and social contexts to aid word learning. Although children with autism disorder (AD) are known to exhibit atypicality in word learning via social eye gaze, their ability to utilize social contexts for word learning is not well understood. We investigated whether verbal AD children exhibit word learning ability via social contextual cues by late childhood. We found that AD children, unlike TD controls, failed to infer the speaker's referential intention through information gathered from the social context. This suggests that TD children can learn words in diverse social pragmatic contexts in as early as toddlerhood whereas AD children are still unable to do so by late childhood. PMID- 24234721 TI - Editorial introduction. PMID- 24234722 TI - Genetic counseling for pregnant adolescents. AB - The genetic counseling literature has a paucity of information on how to provide genetic counseling services to adolescents, especially those who are pregnant. The adolescent population should be viewed as a separate culture, complete with their own beliefs and viewpoints, which are dependent upon the developmental growth tasks of puberty. The completion of these tasks is complicated by pregnancy, which has its own set of developmental goals. The adolescent struggle with developmental goals interferes with the ability to identify consequences, predict future outcomes, and communicate self-revealing statements or decisions effectively. Instead, the adolescent has an egocentric frame of reference and seeks peer approval. The genetic counseling dilemmas presented by pregnant adolescents are illustrated through two case reports. A model based on our own experience and a literature review for successful counseling of adolescents is presented, and utilizes the foundation of trust, patience, and nonjudgmental behavior. Techniques that address the adolescent's concern for autonomy and peer approval are important, and can be achieved through nonthreatening, open-ended questions that promote self-expression. Incorporation of these techniques in genetic counseling and in graduate training will enhance genetic counseling services to the adolescent population. PMID- 24234723 TI - Abstracts of papers and posters presented at the Fifteenth Annual Education Conference of the National Society of Genetic Counselors. PMID- 24234724 TI - Strategies for enhancing occupationally-oriented rehabilitation. PMID- 24234725 TI - Screening for patients at risk of developing chronic incapacity. AB - Formal investigations of psychiatric disorders and long-term personality characteristics have been relatively unhelpful in the prediction of future incapacity. Clinical studies of pain patients have led to a new range of more specific measurement instruments assessing different aspects of psychological functioning: such as pain behavior, distress, beliefs about pain, and coping strategies. Recent investigations of patients with acute back problems have identified a strong relationship between levels of distress, dysfunctional coping strategies, and future disability. Measurement instruments specifically validated for occupational settings still need to be developed, but preliminary studies suggest that fear of hurting/harming, job stress, and job satisfaction may be important factors. A pilot study into occupationally-oriented back pain management for the unemployed is reported. Results suggest that such clients may have significantly more rehabilitation potential than has previously been believed. PMID- 24234726 TI - Demographic, psychometric, and case progression information as predictors of return-to-work in teachers undergoing occupational rehabilitation. AB - Occupational stress is a significant problem and is of particular concern for educational organizations. It was the aim of the current project to identify variables that could predict return-to-work outcomes in a group of teachers who had taken leave for a work-related stress condition. Demographic, psychometric, and case progression data were collected for 119 teachers who had taken Workers' Compensation Leave and were participating in a rehabilitation program. The participants' return to work outcomes were followed-up at least 12 months after they initially left their workplace. Hierarchical discriminant function analysis indicated that 84.62% of the cases could be correctly classified as either "returning to work" or "not returning to work due to illness." The main predictor variables were: if the individual had attempted to return to work within 505 days of injury, the individual's health behaviors, the sex of the individual, and the type of school in which he or she was employed (primary or secondary). It is suggested that the derived model could be further developed and used to predict return to work from stress-related illnesses. PMID- 24234727 TI - The role of fear of movement/(re)injury in pain disability. AB - It is now well established that in chronic low back pain, there is no direct relationship between impairments, pain, and disability. From a cognitive behavioral perspective, pain disability is not only influenced by the organic pathology, but also by cognitive-perceptual, psychophysiological, and motoric environmental factors. This paper focuses on the role of specific beliefs that are associated with avoidance of activities. These beliefs are related to fear of movement and physical activity, which is (wrongfully) assumed to cause (re)injury. Two studies are presented, of which the first examines the factor structure of the Tampa Scale for Kinesiophobia (TSK), a recently developed questionnaire that is aimed at quantifying fear of movement/(re)injury. In the second study, the value of fear of movement/(re)injury in predicting disability levels is analyzed, when the biomedical status of the patient and current pain intensity levels are controlled for. In addition, the determinants of fear of movement/(re)injury are examined. The discussion focuses on the clinical relevance of the fear-avoidance model in relation to risk assessment, assessment of functional capacity, and secondary prevention. PMID- 24234728 TI - Workplace changes in successful rehabilitation. AB - There is a lack of rehabilitation programs that also involve the workplace as a significant variable. Epidemiologic studies have pointed out aspects of the work environment that are risk factors for developing musculoskeletal disorders, delaying return to work, and for promoting relapse. An understanding of risk factors and the ability to identify and alter them is the basis for effective rehabilitation and prevention programs. Workplace changes should comprise organizational and psychosocial aspects, as well as the physical work conditions. Positive attitudes of managers and supervisors toward early return to work need to be emphasized. Several studies stress the importance of new or changed work tasks for a positive prognosis. Opportunities for the individuals to influence their own rehabilitation process may improve the outcome. A promising approach, based on a problem-based rehabilitation strategy, is presented as an attempt to integrate present knowledge from etiologic studies and from rehabilitation studies, respectively. PMID- 24234729 TI - Compliance: A barrier to occupational rehabilitation? AB - While patients' compliance with medical, psychological, and other treatments has received considerable attention the subject has received relatively little attention in the rehabilitation literature. This paper attempts to review the study of patients' compliance in the rehabilitation literature and to examine its role especially in relation to outcomes. The assessment of compliance, some of the factors affecting compliance in rehabilitation, as well as future research issues are also addressed. PMID- 24234731 TI - Current perspectives in genetics of "double-hit" lymphoma with possible clinical implications. AB - This article reviews particular subgroup of B-cell lymphoma, called "double-hit" lymphoma (DHL) because of its distinct aberrations-related genes influencing various processes such as apoptosis, differentiation, and proliferation. Recent studies indicate that tumorigenesis is a complex process involving multiple genes, genetic abnormalities, including gene mutations, deletions, and chromosomal alterations. Chromosomal aberrations are not affecting only basic cellular life preserving activities such as cell proliferation, differentiation, apoptosis, and signal transduction, but are also indispensible for evaluation of lymphoma occurrence, progression, and prognosis as well differential diagnosis and other aspects assessment. DHL is group accompanied by IGH-BCL2 and MYC rearrangement, behaving highly aggressively, with a complex and distinct karyotype which can not be extrapolated solely by morphological pathological assessment, since it has not been entirely characteristic. Therefore, we are reviewing possible effects of multiple genetic rearrangements, particular genes mutations, and developing hypothesis due which pathophysiology mechanisms DHL accomplish synergistic malignant potential. PMID- 24234732 TI - Restoration of optimal ellipsoid left ventricular geometry: lessons learnt from in silico surgical modelling. AB - OBJECTIVES: Several issues that are inherent in the surgical techniques of surgical ventricular restoration (SVR) need specialized devices or techniques to overcome them, which may not always result in optimal outcomes. We used a non invasive novel in silico modelling technique to study left ventricular (LV) morphology and function before and after SVR. The cardiac magnetic resonance imaging derived actual pre- and postoperative endocardial morphology and function was compared with the in silico analysis of the same. METHODS: Cardiac magnetic resonance steady state free precession (SSFP) cine images were employed to segment endocardial surface contours over the cardiac cycle. Using the principle of Hausdorff distance to examine phase-to-phase regional endocardial displacement, dyskinetic/akinetic areas were identified at the instant of peak basal contraction velocity. Using a three-dimensional (3D) surface clipping tool, the maximally scarred, dyskinetic or akinetic LV antero-apical areas were virtually resected and a new apex was created. A virtual rectangular patch was created upon the clipped surface LV model by 3D Delaunay triangulation. Presurgical endocardial mechanical function quantified from cine cardiac magnetic resonance, using a technique of spherical harmonics (SPHARM) surface parameterization, was applied onto the virtually clipped and patched LV surface model. Finally, the in silico model of post-SVR LV shape was analysed for quantification of regional left ventricular volumes (RLVVs) and function. This was tested in 2 patients with post-myocardial infarction antero-apical LV aneuryms. Left ventricular mechanical dysynchrony was evaluated by RLVV analysis of pre-SVR, in silico post-SVR and actual post-SVR LV endocardial surface data. RESULTS: Following exclusion of the scarred areas, the virtual resected LV model demonstrated significantly lesser areas of akinesia. The decreases in regional LV volumes in the in silico modelling were significant and comparable with the actual decreases following SVR. Both the regional end diastolic volume (EDV) and end systolic volume (ESV) at the apex decreased significantly corresponding to greater reductions in apical volumes by the technique of rectangular patch plasty (apical EDV 2.1607 +/- 0.20577 to 0.4774 +/- 0.1775 ml, P = 0.007; apical ESV 1.9708 +/- 0.36451 to 0.442 +/- 0.047 ml, P = 0.013). CONCLUSIONS: This pilot study was done using novel in silico techniques for virtual surgical modelling, which helped in accurate estimation and planning of optimal LV restoration by SVR. PMID- 24234733 TI - Development of ulcer disease after Roux-en-Y gastric bypass, incidence, risk factors, and patient presentation: a systematic review. AB - Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard in bariatric surgery. A long-term complication can be marginal ulceration (MU) at the gastrojejunostomy. The mechanism of development is unclear and symptoms vary. Management and prevention is a continuous subject of debate. The aim was to assess the incidence, mechanism, symptoms, and management of MU after LRYGB by means of a systematic review. Forty-one studies with a total of 16,987 patients were included, 787 (4.6%) developed MU. The incidence of MU varied between 0.6 and 25%. The position and size of the pouch, smoking, and nonsteroidal inflammatory drugs usage are associated with the formation of MU. In most cases, MU is adequately treated with proton pump inhibitors, sometimes reoperation is required. Laparoscopic approach is safe and effective. PMID- 24234734 TI - Nonsurgical management of luminal dilatation after laparoscopic adjustable gastric banding. AB - BACKGROUND: Proximal luminal dilatation (PLD) is one of the most significant challenges following laparoscopic adjustable gastric banding (LAGB). If PLD is identified at an early stage, there is potential to avoid reoperation or irreversible change by implementing nonsurgical measures. The success of these strategies is unknown. The aim of this study was to determine the outcome of how often PLD can be successfully treated nonsurgically. METHODS: The records of patients who underwent primary LAGB insertion by a single surgeon from January 2005 to December 2006 were reviewed. Study participants were all patients who had subsequently undergone a postoperative liquid contrast swallow demonstrating a PLD. The severity of PLD, subsequent management, and outcomes were recorded and assessed. RESULTS: There were 354 patients who underwent a primary LAGB insertion during the study period. Seventy-eight patients were found to have varying degrees of PLD and had an attempt at nonsurgical management. Thirty-four of these patients (43.6 %) were successfully managed nonsurgically at a mean follow-up of 2.8 years (33.2 months, CL +/- 3.2). The success with nonsurgical management was lower if the symmetrical pouch dilatation was more severe or gastric prolapse was seen at presentation, and if no improvement in liquid contrast swallow was seen. CONCLUSIONS: PLD can often be successfully managed with nonsurgical measures, maintaining good weight loss in the intermediate term. Patients with more significant dilatation are more likely to require revisional surgery. Early recognition may have a role in preventing surgery or more severe abnormalities. PMID- 24234735 TI - Weight loss percentile charts of large representative series: a benchmark defining sufficient weight loss challenging current criteria for success of bariatric surgery. AB - BACKGROUND: The frequently used 35 kg/m2 body mass index (BMI) and 50 % excess weight loss (%EWL) criteria are no longer adequate for defining the success of a bariatric or metabolic surgery. It is not clear whether they are still useful to simply determine the sufficiency of a patient's postoperative weight loss. An alternative way of defining sufficient weight loss is presented, using weight loss percentile charts of large representative series as a benchmark. METHODS: Gastric bypass weight loss results from the Bariatric Outcomes Longitudinal Database (BOLD) with >=2 years of follow-up are presented with percentiles in function of postoperative time and their nadir results in function of initial BMI using different outcome metrics. These percentiles are compared with the BMI35 and 50%EWL criteria. RESULTS: Of 49,098 patients eligible for >=2 years of follow up, 8,945 had reported weight loss at >=2 years (20.0% male, mean initial BMI 47.7 kg/m2). They reached nadir BMI at a mean of 603 days. Their 50th percentiles surpassed both 50 %EWL and BMI35 after 135 days. More than 95% achieved 50% EWL; more than 75% achieved BMI35. BMI and %EWL results are influenced more by initial BMI than total weight loss (%TWL) results. CONCLUSIONS: BOLD gastric bypass weight loss data are presented with percentile curves. BMI and %EWL are clearly not suited for this purpose. Provided that follow-up data are solid, %TWL-based percentile charts can constitute neutral benchmarks for defining sufficient postoperative weight loss over time. Criteria for overall success, however, should consider clear goals of health improvement, including metabolic aspects. Frequently used criteria 50% EWL and BMI35 are inadequate for both. Their static weight loss components do not match the found percentiles and their health improvement components do not match known metabolic criteria. PMID- 24234736 TI - Patient investigation of average glandular dose and incident air kerma for digital mammography. AB - Our aim in this study was to investigate the incident air kerma (IAK) and average glandular dose (AGD) for polymethylmethacrylate (PMMA) phantoms and patient breasts for each thickness by use of digital mammography units, and to determine the correlation between phantom and patient measurements. An additional aim was to calculate the numerical value of the diagnostic reference level (DRL) for digital mammography in Japan based on the AGD from patient measurements. Patient based IAK and AGD values were calculated for 300 patients who underwent mammographic examinations at three institutions. On examination of a 40-mm PMMA phantom, the IAK and the AGD were 7.89 and 1.84 mGy, respectively. The mean patient breast thickness was 37.6 mm, and the mean IAK and the AGD calculated from actual patient data for breast thicknesses between 40 mm and 50 mm were 8.91 and 2.08 mGy, respectively. Approximately 20 % of the 300 patients had IAK >10 mGy. The distributions of patient-based IAK and AGD values were higher than the IAK and AGD values for the PMMA phantom. The patient dose with use of the PMMA phantom can be underestimated. The DRL was calculated from patient-based AGDs of the regular breast thickness as 2.0 mGy in Japan. PMID- 24234737 TI - JASMS to 12 issues means faster turnaround. PMID- 24234738 TI - High-resolution mass spectrometry of large molecules in a linear time-of-flight mass spectrometer. AB - This report describes a new high-resolution linear time-of-flight mass spectrometer that has been constructed at this institute. The instrument is used for investigations of both direct and matrix-assisted laser desorption/ionization of large molecules. A unique feature of this new instrument is the incorporation of a 10-cm postsource pulse-focusing region for enhancing the resolution of the detected ion signals. This technique can correct for both high initial ion translational energies and long durations of ion formation and is expected to be particularly well suited for laser desorption/ionization applications. Results of calculations are presented to illustrate the gains in mass resolution that may be expected for a variety of ion formation conditions. In addition, initial experimental results are presented that demonstrate the capability of this new instrument to produce high-resolution ion signals. Signals with mass resolutions as high as 2750 (full width at half maximum) have been obtained for both direct and matrix-assisted laser desorption/ionization signals. PMID- 24234739 TI - The effect of ion size on rate of dissociation: RRKM calculations on model large polypeptide ions. AB - The larger an ion is, the less likely it is to decompose on mass spectrornetry time scales at given critical and internal energies. This is an obstacle to obtaining structural information on large molecules by mass spectrometry. We performed RRKM calculations on model ions with masses from 0.27 kDa to 102.4 kDa to explore what such calculations predict regarding this limitation. According to the calculations, it is impractical to add enough energy to fragment very large ions unless the decomposition has a low critical energy. It is suggested that ion molecule reactions that are either very low in their critical energies or exothermic may be a feasible approach to fragmenting ionized macromolecules. PMID- 24234740 TI - Inductively coupled plasma mass spectrometry with an enlarged sampling orifice and offset Ion Lens. I. Ion trajectories and detector performance. AB - A new inductively coupled plasma mass spectrometer (ICP-MS) with four stages of differential pumping is described. The relatively large sampling orifice (1.31-mm dia.) improves signals for metal ions and resists plugging from deposited solids. A new ion lens is described that deflects ions off center and then back on center into the differential pumping orifice; there is no photon stop in the center of the beam. Calculations of ion trajectories using SIMIOn show that only those ions that leave the skimmer on center are transmitted, whereas most other lenses used in ICP-MS transmit only ions that leave the skimmer off axis. The performance of a Channeltron electron multiplier is compared to that of a Daly detector. Both detectors yield similar sensitivities of ~ 10(6) counts s(-1) per ppm and detection limits of ~ 1 pptr. The background with a Channeltron electron multiplier is only 0.4 counts s(-1) and is only slightly higher than the dark current count rate. Presumably the offset ion lens used in the present work efficiently screens the detector from photons emitted by the plasma. The background with the Daly detector is 4 counts s(-1), which represents a substantial improvement over the background obtained in previous use of the Daly detector with JCP-MS. PMID- 24234741 TI - Inductively coupled plasma mass spectrometry with an enlarged sampling orifice and offset ion lens. II. Polyatomic Ion interferences and matrix effects. AB - A new inductively coupled plasma mass spectrometer with an enlarged sampling orifice (1.31-mm dia.) and an offset ion lens yields very low levels of many troublesome polyatomic ions such as ArO(+), ArN(+), Ar2 (+), ClO(+), and ArCl(+). The signals from refractory metal oxide ions are ~ 1% of the corresponding metal ion signals, which is typical of most ICP-MS devices. Grounding the first electrode of the ion lens greatly reduces the severity of matrix effects to <- 20% loss in signal for Co(+), Y(+), or Cs(+) in the presence of 10 mM Sr, Tm, or Pb. This latter lens setting causes only a modest loss (30%) in sensitivity for analyte elements compared to the best sensitivity obtainable by biasing the first lens. Alternatively, matrix effects can also be mitigated by readjusting the voltage applied to the first lens with the matrix present. PMID- 24234742 TI - Coupling a particle beam interface directly to a quadrupole ion trap mass spectrometer. AB - A particle beam interface has been coupled to a quadrupole ion trap mass spectrometer. The system allows the collection of electron ionization mass spectra from analyte in solution. The interface incorporates a pneumatic nebulizer, a heated desolvation chamber, and a three-stage separator region. Additional helium, for improved performance, is added through stage 3. The particles formed in the interface are separated from solvent molecules and are transferred directly to the ion trap where they are expected to collide with the hot hyperbolic surface of the end cap. The end cap serves both as a heated target used to vaporize the particles and as an ion-trapping electrode. Mass analysis is achieved with the mass-selective instability scan supplemented with resonance ejection. Electron ionization spectra from 100 ng of caffeine [molecular weight (MW) = 1941; 1-naphthalenol methylcarbamate (carbaryl) (MW = 2011, 17alpha hydroxyprogesterone (MW = 330), and reserpine (MW = 608) are shown using sampling by a segmented flow analysis. Some charge exchange is evident with methanol as well as self-chemical ionization at higher analyte levels. The interface shows a nonlinear caffeine calibration curve for analyte amounts below 30 ng and a more linear response at higher amounts. Caffeine was detected at 25 pmol (5 ng), with a signal-to-noise ratio of 50, 20-MUL loop, full scan. PMID- 24234743 TI - Analysis of solution residues by glow discharge mass spectrometry. AB - A technique for the analysis of microliter volumes of solution by glow discharge mass spectrometry (GDMS) has been successfully demonstrated. Cathode preparation involves mixing an aliquot of the sample solution with a pure conducting powder, followed by drying and pressing before conventional GDMS analysis. The analyte signal at the 100-ppm level was observed to be stable to better than 5% for the duration of the analysis (30-45 min). Internal and external reproducibilities were better than 5%, and the ion signal intensity was linear with concentration over at least four orders of magnitude. Quantification was demonstrated by means of user-defined relative sensitivity factors. Relative standard deviations were better than 15% for the elements investigated, with no preconcentration of the analyte. PMID- 24234744 TI - Fourier transform-ion cyclotron resonance study of the gas-phase acidities of germane and methylgermane; Bond dissociation energy of germane. AB - An accurate gas-phase acidity for germane (enthalpy scale, equivalent to the proton affinity of GeH3 (-)), DeltaH acid (o)(GeH4) = 1502.0 +/- 5.1 kJ mol(-1), is obtained by constructing a consistent acidity ladder between GeH4, and H2S by using Fourier transform-ion cyclotron resonance spectrometry, and 0 and 298.15 K values for the first bond dissociation energy of GeH4 are proposed: D0 (o)(H3Ge H) = 352 +/- 9 kJ mol(-1); D (o)(H3Ge-H) = 358 +/- 9 kJ mol(-1), respectively. These results are compared with experimental and theoretical data reported in the literature. Methylgermane was found to be a weaker acid than germane by approximately 35 kJ mol(-1): DeltaH acid (o) = 1536.6 kJ mol(-1). PMID- 24234745 TI - Comparative study of the gas-phase bond strengths of CO2 and N 2O with the halide ions. AB - Thermodynamic data, DeltaH n-1, n (o) and DeltaS n-1, n (o), for clustering reactions of halide ions X(-)(X = F, Cl, Br, and I) with N2Owere measured with a pulsed electron beam high-pressure mass spectrometer. In contrast to the fact that CO2 forms a covalent bond with the fluoride ion to yield the fluoroformate ion, FCO2 (-), the interaction between F(-) and N2O is mainly electrostatic. It was found that the cluster ions F(-) (N2O)n complete the first shell at n = 6, thus forming an octahedral structure. The difference between F-CO2 (-) and F(-) ... N2O is discussed in terms of Coulombic, exchange, and charge-transfer interactions. The X(-) (N2O)2 clusters (X = Cl, Br and I) are found to be of C2h symmetry, while F(-) (N2O)2 is of a twisted form and is slightly asymmetric due to a slight participation of covalency (charge transfer) in the core ion F(-) ... N2O. PMID- 24234746 TI - Unimolecular photochemistry of n-alkenes studied by photodissociation photoionization mass spectrometry. AB - The 193-nm unimolecular photochemistry of n-alkenes from C5 to C14 is studied by photodissociation-photoionization mass spectrometry (PDPI/MS). In PDPI/MS, a UV laser induces neutral unimolecular photodissociation. The resulting neutral fragments and any remaining parent molecules are then softly ionized with coherent vacuum UV radiation and mass analyzed. Photodissociation of n-alkenes is dominated by cleavage of the beta C-C bond. Products of alpha- and gamma-cleavage are typically less than 20% as abundant as the beta-cleavage fragments. Secondary fragmentation of the primary products occurs both by neutral fragmentation during photodissociation and by ionic fragmentation during photoionization. The energetics of the neutral secondary reactions indicate that between 400 and 500 kJ/mol is consumed during photodissociation. The abundances of many secondary fragmentation products decrease with increasing molecular size. Because neutral fragmentation occurs without significant isomerization, PDPI/MS provides structural information that is not available from ionic fragmentation in conventional mass spectrometric experiments. PMID- 24234747 TI - Gas-phase reactions between O(-.) and C 6H 5F: On the acidity of fluorobenzene and 1,4-difluorobenzene. AB - The gas-phase reactions of negative ions (O(-.), NH 2 (-) , C2H5NH(-), (CH3)2N( ), C6H 5 (t-) , and CH3SCH 2 (-) ) with fluorobenzene and 1,4-difluorobenzene have been studied with Fourier transform ion cyclotron resonance mass spectrometry. The O(-.) ion reacts predominantly by (1) proton abstraction, (2) formal H 2 (+.) abstraction, and (3) attack on an unsubstituted carbon atom. In addition to these processes, attack on a fluorine bearing carbon atom yielding F( ) and C6H4FO(-) ions occurs with 1,4-difluorobenzene. Site-specific deuterium labeling reveals the occurrence of competing 1,2-, 1,3-, and 1,4-H 2 (+.) abstractions in the reaction of O(-.) with fluorobenzene. Attack of the O(-.) ion on the 3- and 4-positions in fluorobenzene with formation of the 3- and 4 fluorophenoxide ions, respectively, is preferred to reaction at the 2-position, as indicated by the relative extent of loss of a hydrogen and a deuterium atom in the reactions with labeled fluorobenzenes. The NH 2 (-) , C2H5NH(-), (CH3)2N(-), C6H 5 (-) , and CH3SCH 2 (-) anions react with fluoroberuene and 1,4 difluorobenzene only by proton abstraction. The relative importance of H(+) and D(+) abstraction in the reaction of these anions with labeled fluorobenzenes indicates that the 2-position in fluorobenzene is more acidic than the 3- and 4 positions, suggesting that the literature value of the gas-phase acidity of this compound (DeltaH acid (o) = 1620 +/- 8 kJ mol(-1)) refers to the former site. Based on the occurrence of reversible proton transfer between the CH3O(-) ion and 1,4-difluorobenzene, the DeltaH acid (o) of this compound is redetermined to be 1592 +/- 8 kJ mol(-1). PMID- 24234749 TI - Erratum to: The mass spectrometry of taxol. PMID- 24234750 TI - Characterization of an acid inducible lipase Rv3203 from Mycobacterium tuberculosis H37Rv. AB - The Rv3203 (LipV) of Mycobacterium tuberculosis (Mtb) H37Rv, is annotated as a member of Lip family based on the presence of characteristic consensus esterase motif 'GXSXG'. In vitro culture studies of Mtb H37Ra indicated that expression of Rv3203 gene was up-regulated during acidic stress as compared to normal whereas no expression was observed under nutrient and oxidative stress conditions. Therefore, detailed characterization of Rv3203 was done by gene cloning and its further expression and purification as his-tagged protein in microbial expression system. The enzyme was purified to homogeneity by affinity chromatography. It demonstrated broad substrate specificity and preferentially hydrolyzed p nitrophenyl myristate. The purified enzyme demonstrated an optimum activity at pH 8.0 and temperature 50 degrees C. The specific activity, K m and V max of enzyme was determined to be 21.29 U mg(-1) protein, 714.28 MUM and 62.5 MUmol ml(-1) min(-1), respectively. The pH stability assay and circular dichroism spectroscopic analysis revealed that Rv3203 protein is more stable in acidic condition. Tetrahydrolipstatin, a specific lipase inhibitor and RHC80267, a diacylglycerol lipase inhibitor abolished the activity of this enzyme. The catalytic triad residues were determined to be Ser50, Asp180 and His203 residues by site-directed mutagenesis. PMID- 24234751 TI - Differences in the expression pattern of HCN isoforms among mammalian tissues: sources and implications. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in a broad range of cell types, but the expression of the various HCN isoforms is still poorly understood. In the present study we have compared the expression of HCN isoforms in rat excitable and non-excitable tissues at both the mRNA and protein levels. Real-time PCR and Western blot analysis revealed distinct expression patterns of the four HCN isoforms in brain, heart, pituitary and kidney, with inconsistent mRNA-protein expression correlation. The HCN2 was the most abundant mRNA transcript (95.6, 78.0 and 59.0 % in kidney heart and pituitary, respectively) except in the brain (42.0 %) whereas HCN4 was the most abundant protein isoform. Our results suggest that HCN channels are mostly produced by the HCN4 isoform in heart, which contrasts with the sharp differences in the isoform stoichiometry in pituitary (15 HCN4:2 HCN2:1 HCN1:1 HCN3), kidney (24 HCN4:2 HCN3:1 HCN2:1 HCN1) and brain (3 HCN4:2 HCN2:1 HCN1:1 HCN3). Moreover, deviations of the electrophoretic molecular weight (MW) of the HCN isoforms relative to the theoretical MW were observed, suggesting that N-glycosylation and enzymatic proteolysis influences HCN channel surface expression. We hypothesize that selective cleavage of HCN channels by membrane bound metalloendopeptidases could account for the multiplicity of properties of native HCN channels in different tissues. PMID- 24234752 TI - Association between polymorphism in TRAF1/C5 gene and risk of rheumatoid arthritis: a meta-analysis. AB - Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease. Single nucleotide polymorphisms of tumor necrosis factor-receptor associated factor 1/complement component 5 (TRAF1/C5) gene are suspected to be associated with the risk of RA. This meta-analysis was performed to study the relationship between the polymorphism rs10818488 in TRAF1/C5 gene with RA. We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure databases. Odd ratios were calculated to assess the association between TRAF1/C5 rs10818488 polymorphism and RA risk. Meta-analyses were performed on the total data set and separately for the major ethnic groups and RF and ACAP status. All analyses were performed using the Stata software. Eight articles were included in the present analysis. Meta-analysis showed a weak association between TRAF1/C5 rs10818488 polymorphism and RA in all subjects (OR = 1.13, 95 % CI = 1.01-1.27, P heterogeneity < 0.001). Stratified analyses indicated that the TRAF1/C5 rs10818488 A allele was significantly associated with RA in Caucasians (OR = 1.29, 95 %CI = 1.14-1.47, P heterogeneity = 0.026), Asians (OR = 0.92, 95 %CI = 0.86-0.99, P heterogeneity = 0.378) and Africans (OR = 1.56, 95 %CI = 1.23-1.98, P heterogeneity = 0.876), also significantly in positive ACPA and positive RF patients versus controls (ORs were 1.20 and 1.25, 95 %CIs were 1.08-1.33 and 1.14-1.37, P values for heterogeneity were 0.215 and 0.133, respectively). Genetic polymorphism rs10818488 in TRAF1/C5 gene might be associated with RA susceptibility. PMID- 24234753 TI - Interactions of ketoamide inhibitors on HCV NS3/4A protease target: molecular docking studies. AB - HCV infection in more than 200 million individuals worldwide is a principal health problem. Prior to the development of HCV protease inhibitor combination therapy, HCV infected patients were treated with pegylated interferon-alpha and ribavirin. The adverse side effects associated with this type of treatment may lead to the discontinuation of treatment in certain number of patients. Currently, the inhibitors of NS3/4A Protease were found promising candidates for the treatment of HCV infection. There are several inhibitors of HCV NS3/4A protease that are passing through clinical improvement showing good potency against HCV infections in a number of patients. To further recognize binding interactions and activity trend, the molecular docking studies were performed on a number of HCV NS3/4A protease ketoamide inhibitors via MOE docking protocol. The docking analysis resulted in the detection of important ligand interactions with respect to binding site of target protein and produced good correlation coefficient (r2 = 0.690) between docking score and biological activities. These molecular docking results should, in our view, contribute for further optimization of ketoamide derivatives as NS3/4A protease inhibitors. PMID- 24234754 TI - Functional models for colloid retention in porous media at the triple line. AB - Spectral confocal microscope visualizations of microsphere movement in unsaturated porous media showed that attachment at the Air Water Solid (AWS) interface was an important retention mechanism. These visualizations can aid in resolving the functional form of retention rates of colloids at the AWS interface. In this study, soil adsorption isotherm equations were adapted by replacing the chemical concentration in the water as independent variable by the cumulative colloids passing by. In order of increasing number of fitted parameters, the functions tested were the Langmuir adsorption isotherm, the Logistic distribution, and the Weibull distribution. The functions were fitted against colloid concentrations obtained from time series of images acquired with a spectral confocal microscope for three experiments performed where either plain or carboxylated polystyrene latex microspheres were pulsed in a small flow chamber filled with cleaned quartz sand. Both moving and retained colloids were quantified over time. In fitting the models to the data, the agreement improved with increasing number of model parameters. The Weibull distribution gave overall the best fit. The logistic distribution did not fit the initial retention of microspheres well but otherwise the fit was good. The Langmuir isotherm only fitted the longest time series well. The results can be explained that initially when colloids are first introduced the rate of retention is low. Once colloids are at the AWS interface they act as anchor point for other colloids to attach and thereby increasing the retention rate as clusters form. Once the available attachment sites diminish, the retention rate decreases. PMID- 24234755 TI - SimPhy: a simulation game to lessen the impact of phytosanitaries on health and the environment--the case of Merja Zerga in Morocco. AB - Diffuse phytosanitary pollution is a complex phenomenon to manage. Reducing this type of pollution is one of today's key socio-economic and environmental challenges. At the regional level, few approaches enable the actors concerned to implement agricultural management strategies to reduce the use and impact of phytosanitary products. Our research problem focused on the consequences of intensive agriculture and, in particular, how to evaluate the impact of phytosanitary products on human health and the environment. In this article, we present the SimPhy simulation game which places the actors from a given region directly into a situation in which they manage farms whilst under pressure to reduce phytosanitaries (quantity and toxicity). The application focused on the Merja Zerga catchment area in Morocco. The region is dominated by intensive agriculture which is located upstream from a Ramsar-classified wetland area. The SimPhy simulation game is based on a decision support system-type tool. It allows us to anticipate the impact of regulations on farming systems. It also enables us to analyse the consequences of the actors' strategies on farm economies, human health and the quality of ecosystems. Initial results from the SimPhy simulation game enabled the technicians from Agricultural Development Center (CDA) themselves to learn about managing agricultural production systems in a dynamic and interactive fashion. With the simulation game, it was possible to learn about the farmer's ability to adapt to new regulatory constraints, and the involved consequences for toxicity risks for human health and the environment. PMID- 24234756 TI - Trophic transfer and accumulation of mercury in ray species in coastal waters affected by historic mercury mining (Gulf of Trieste, northern Adriatic Sea). AB - Total mercury (Hg) and monomethylmercury (MMHg) were analysed in the gills, liver and muscle of four cartilaginous fish species (top predators), namely, the eagle ray (Myliobatis aquila), the bull ray (Pteromylaeus bovinus), the pelagic stingray (Dasyatis violacea) and the common stingray (Dasyatis pastinaca), collected in the Gulf of Trieste, one of the most Hg-polluted areas in the Mediterranean and worldwide due to past mining activity in Idrija (West Slovenia). The highest Hg and MMHg concentrations expressed on a dry weight (d.w.) basis were found in the muscle of the pelagic stingray (mean, 2.529 mg/kg; range, 1.179-4.398 mg/kg, d.w.), followed by the bull ray (mean, 1.582 mg/kg; range, 0.129-3.050 mg/kg d.w.) and the eagle ray (mean, 0.222 mg/kg; range, 0.070 0.467 mg/kg, d.w.). Only one specimen of the common stingray was analysed, with a mean value in the muscle of 1.596 mg/kg, d.w. Hg and MMHg contents in the bull ray were found to be positively correlated with species length and weight. The highest MMHg accumulation was found in muscle tissue. Hg and MMHg were also found in two embryos of a bull ray, indicating Hg transfer from the mother during pregnancy. The number of specimens and the size coverage of the bull rays allowed an assessment of Hg accumulation with age. It was shown that in bigger bull ray specimens, the high uptake of inorganic Hg in the liver and the slower MMHg increase in the muscle were most probably due to the demethylation of MMHg in the liver. The highest Hg and MMHg contents in all organs were found in the pelagic stingray, which first appeared in the northern Adriatic in 1999. High Hg and MMHg concentrations were also found in prey species such as the banded murex (Hexaplex trunculus), the principal prey of the eagle rays and bull rays, the anchovy (Engraulis encrasicholus) and the red bandfish (Cepola rubescens), which are preyed upon by the pelagic stingray, as well as in zooplankton and seawater. Based on previously published data, a tentative estimation of MMHg bioamagnification was established. The average increase in MMHg between seawater, including phytoplankton, and zooplankton in the Gulf was about 10(4), and MMHg in anchovy was about 50-fold higher than in zooplankton. The bioaccumulation of MMHg between seawater and small pelagic fish (anchovy) amounted to 10(6) and between water and the muscle of larger pelagic fish (pelagic stingray) to 10(7). The MMHg increase between surface sediment and benthic invertebrates (murex) and between benthic invertebrates and small benthic fish was 10(2). Ultimately, the trophic transfer resulted in a 10(3) accumulation of MMHg between water and muscle of larger benthic fish (bull ray, eagle ray, common stingray), suggesting lower bioaccumulation by benthic feeding species. PMID- 24234757 TI - The effect of structural compositions on the biosorption of phenanthrene and pyrene by tea leaf residue fractions as model biosorbents. AB - To enhance the removal efficiency of polycyclic aromatic hydrocarbons (PAHs) by natural biosorbent, sorption of phenanthrene and pyrene onto raw and modified tea leaves as a model biomass were investigated. Tea leaves were treated using Soxhlet extraction, saponification, and acid hydrolysis to yield six fractions. The structures of tea leaf fractions were characterized by elemental analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The amorphous cellulose components regulated the sorption kinetics, capacity, and mechanism of biomass fractions. The adsorption kinetics fit well to pseudo-second-order model and isotherms followed the Freundlich equation. By the consumption of the amorphous cellulose under acid hydrolysis, both the aliphatic moieties and aromatic domains contributed to total sorption, thus sorption capacities of the de-sugared fractions were dramatically increased (5-20-fold for phenanthrene and 8-36-fold for pyrene). All de-sugared fractions exhibited non linear sorption due to strong specific interaction between PAHs and exposed aromatic domains of biosorbent, while presenting a relative slow rate because of the condensed domain in de-sugared samples. The availability of strong sorption phases (aromatic domains) in the biomass fractions were controlled by polar polysaccharide components, which were supported by the FTIR, CHN, and SEM data. PMID- 24234759 TI - Efficient degradation of phenol using natural clay as heterogeneous Fenton-like catalyst. AB - A natural containing Fe-clay (NRC) was used for the Fenton-like oxidation of phenol. This new catalyst was very efficient in phenol elimination in aqueous medium under mild experimental conditions (20 degrees C, atmospheric pressure and low concentration of hydrogen peroxide). The influence of different parameters like calcination's temperature, particle size, initial phenol and H2O2 concentrations were examined considering both phenol conversion and total organic carbon (TOC) removal. NRC was characterized by several complementary methods including chemical analysis, X-ray diffraction (XRD), Mossbauer spectroscopy, thermogravimetry-differential thermal analysis (TG-DTA), temperature programmed reduction (TPR) and BET. The experimental results showed that 100 % phenol conversion and 70 % TOC removal can be achieved using sieved and calcined NRC (d < 50 MUm/450 degrees C). Catalytic activity of NRC was mainly attributed to the amount of iron oxide species (12.15 wt.%) present naturally in the clay. PMID- 24234758 TI - Sorption/desorption behavior of oxytetracycline and sulfachloropyridazine in the soil water surfactant system. AB - Sorption/desorption of antibiotics, oxytetracycline (OTC), and sulfachloropyridazine (SCP) was investigated in the presence of a nonionic surfactant Brij35. Batch sorption experiments indicated that Freundlich equation fits sorption isotherms well for OTC. The sorption coefficients, KF, values were computed as 23.55 mL g(-1) in the absence of Brij35 and 25.46 mL g(-1) in the presence of Brij35 in the monomer form (below critical micelle concentration CMC, of 74 mg L(-1)). However, the KF values reduced to 12.76 mL g(-1) in the presence of Brij35 at 2.5 g L(-1). Therefore, irrigation with surfactant-rich water may increase the leaching potential of OTC. In the case of SCP, the KF value, in the absence of Brij35, was 19.95 mL g(-1). As a result of increasing the concentration of Brij35 to 0.25 g L(-1) (about 2.5 CMC), KF values first increased and reached a maximum value of 95.49 mL g(-1) and then reduced to 66.06 mL g(-1), at surfactant concentration of 5 g L(-1). Unlike OTC, the presence of surfactant in irrigation water is likely to decrease SCP leaching. In the case of OTC, hysteresis was found at Brij35 concentrations below CMC. However, OTC desorbed readily from soil (no hysteresis) at Brij35 concentrations above CMC. In the case of SCP, no hysteresis was found in the presence of the surfactant, both below and above CMC. Further, the obtained values of the efficiency coefficient (E), reveals that Brij35 had the potential to release more OTC from the soil (E > 1) as compared to SCP (E < 1). From these results, it can be concluded that regular use of manure on agricultural soils, especially in regions where poor quality irrigation water is used, can increase OTC contamination of water resources. PMID- 24234760 TI - Seasonal variations in the chemical composition of particulate matter: a case study in the Po Valley. Part II: concentration and solubility of micro- and trace elements. AB - Size distribution (fine and coarse fraction) and solubility distribution (extracted and residual fraction) of 20 elements (As, Ba, Be, Cd, Co, Cu, Fe, Li, Mn, Pb, Ni, Rb, S, Sb, Se, Sn, Sr, Ti, Tl, V) in atmospheric particulate matter (PM) were determined during a 5-year field study carried out in the Po Valley (peri-urban area of Ferrara, in Northern Italy). By studying the contribution of the two size fractions and the two solubility fractions to the atmospheric concentration of each element, it was possible to obtain interesting information about the variability of PM sources, to assess the role played by atmospheric stability in determining pollution episodes, and to obtain an estimate of the bio accessible fraction. Atmospheric stability is confirmed to be one of the main causes of atmospheric pollution in this area and is to be responsible for the pronounced winter increase in both PM and elemental concentration. Long-range transport of natural and polluted air masses caused temporary increases in PM and elemental concentration, while local industrial emission seemed to play a secondary role. Regulated elements were well below their concentration limit, but many toxic elements were in the form of fine particles and soluble chemical species, more accessible to the environment, and the human body. PMID- 24234761 TI - Large-scale geographical variation in eggshell metal and calcium content in a passerine bird (Ficedula hypoleuca). AB - Birds have been used as bioindicators of pollution, such as toxic metals. Levels of pollutants in eggs are especially interesting, as developing birds are more sensitive to detrimental effects of pollutants than adults. Only very few studies have monitored intraspecific, large-scale variation in metal pollution across a species' breeding range. We studied large-scale geographic variation in metal levels in the eggs of a small passerine, the pied flycatcher (Ficedula hypoleuca), sampled from 15 populations across Europe. We measured 10 eggshell elements (As, Cd, Cr, Cu, Ni, Pb, Zn, Se, Sr, and Ca) and several shell characteristics (mass, thickness, porosity, and color). We found significant variation among populations in eggshell metal levels for all metals except copper. Eggshell lead, zinc, and chromium levels decreased from central Europe to the north, in line with the gradient in pollution levels over Europe, thus suggesting that eggshell can be used as an indicator of pollution levels. Eggshell lead levels were also correlated with soil lead levels and pH. Most of the metals were not correlated with eggshell characteristics, with the exception of shell mass, or with breeding success, which may suggest that birds can cope well with the current background exposure levels across Europe. PMID- 24234762 TI - Effect of biogas sparging with different membrane modules on membrane fouling in anaerobic submerged membrane bioreactor (AnSMBR). AB - This study focused on the effect of biogas sparging and different membrane modules such as cylinder shaped, funnel-shaped, and U-shaped on the membrane fouling behavior in a lab-scale submerged anaerobic membrane bioreactor (AnSMBR) which was operated for over 60 days. In order to investigate the membrane fouling behavior, a series of analysis such as SMP, EPS, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), particle size distribution, and filtration resistances were performed. Although the rapid generation of cake layer took placed in case of the absence of biogas sparging, the membrane module design mostly influenced the membrane resistance when biogas sparging was applied. Total resistance was the highest for U-shaped module. The permeate fluxes with biogas sparging were higher about one half and two times than those without biogas sparging. Cylinder-shaped module had the lowest SMP and EPS concentrations followed by U-shaped and funnel-shaped modules under both cases with and without biogas sparging. The total resistances of all membrane modules without biogas sparging were found to be very high compared the pore blocking resistances (Rp). PMID- 24234764 TI - Potential interventions and other considerations for patients with Alzheimer's disease. PMID- 24234763 TI - Potential for phytoextraction of copper by Sinapis alba and Festuca rubra cv. Merlin grown hydroponically and in vineyard soils. AB - The extensive use of copper-bearing fungicides in vineyards is responsible for the accumulation of copper (Cu) in soils. Grass species able to accumulate Cu could be cultivated in the vineyard inter-rows for copper phytoextraction. In this study, the capacity of Festuca rubra cv Merlin and Sinapis alba to tolerate and accumulate copper (Cu) was first investigated in a hydroponic system without the interference of soil chemical-physical properties. After the amendment of Cu (5 or 10 mg Cu l-(1)) to nutrient solution, shoot Cu concentration in F. rubra increased up to 108.63 mg Cu kg(-1) DW, more than three times higher than in S. alba (31.56 mg Cu kg(-1) DW). The relationship between Cu concentration in plants and external Cu was dose-dependent and species specific. Results obtained from the hydroponic experiment were confirmed by growing plants in pots containing soil collected from six Italian vineyards. The content of soil organic matter was crucial to enhance Cu tolerance and accumulation in the shoot tissues of both plant species. Although S. alba produced more biomass than F. rubra in most soils, F. rubra accumulated significantly more Cu (up to threefold to fourfold) in the shoots. Given these results, we recommended that F. rubra cv Merlin could be cultivated in the vineyard rows to reduce excess Cu in vineyard soils. PMID- 24234768 TI - Phenylalanine fluorescence and phosphorescence used as a probe of conformation for cod parvalbumin. AB - The fluorescence emission and triplet absorption properties of phenylalanine in cod fish parvalbumin type II, a protein that contains no Trp or Tyr, was examined in the time scale ranging from nanoseconds to microseconds at 25 degrees C in aqueous buffer (pH 7.0). In the presence of Ca(II), the decay of fluorescence gave two lifetimes (5.9 and 53 ns) and the triplet lifetime was 425 MUs. Upon removal of Ca, the fluorescence intensity decreased to values approaching that for free Phe, while the longest fluorescence decay component was 17 ns. At the same time, the decay of triplet showed complex nonexponential kinetics with decay rates faster than in the presence of Ca. Quenching and denaturation analyses suggest that the Phe's are present in a hydrophobic environment in the Ca-bound protein but that the Ca-free protein is relatively unstructured. It is concluded that Phe luminescence in proteins is sensitive to conformation and that the long lifetime of Phe excited states needs to be considered when studying its photochemistry in proteins. PMID- 24234769 TI - Structural requirements for efficient photoinduced electron transfer (PET) quenching in 9-aminoalkylanthracenes. AB - The structure-quenching relationship in 9-aminoalkylanthracenes is examined by the synthesis and fluorescence evaluation of five derivatives; it is observed that benzylic 2 degrees and 3 degrees amines lead to >=95% quenching of anthracene fluorescence in water, while other amines afford substantially lower quenching efficiencies. PMID- 24234770 TI - Synthesis and characterization of a solvatochromic, lipophilic fluorescent oxazone: 1-Pentyl-7-dimethylamino-3H-phenoxazine-3-one. AB - Olivetol and 4-nitroso-N,N-dimethylaniline were combined under reflux in acetic acid to produce 1-pentyl-7-dimethylamino-3H-phenoxazine-3-one (1-PDMPO). The fluorescent behavior of the purified compound in a variety of solutions and samples was investigated. Excitation and emission spectra in pure solvents and mixtures of solvents demonstrate solvatochromism, indicating that the fluorescence response of this compound is affected by its environment. Nonpolar, aprotic solvents as well as protic, polar solvents diminish fluorescent emission in the spectral regions examined, and trends in the fluorescence decary lifetimes measured in five pure solvents are consistent with these intensity changes. The anisotropy excitation spectrum taken in glycerol for 1-PDMPO at -15 degrees C appears to be consistent with the presence of a single electronic state upon excitation, with anisotropy values approaching 0.35 over 400-600 nm. Fluorescence emission is also diminished at low acid concentrations in methanol, with smaller decreases observed in more highly concentrated basic solutions. Emission peaks in aqueous sodium dodecyl sulfate solutions, extruded egg phosphatidylcholine vesicles, and fatty acid free bovine serum albumin suspensions all lie above 600 nm, with emission in the albumin suspension displaying a broad shoulder extending to 800 nm. The fluorescent properties of this compound suggest that it or structural homologues may have utility as fluorescent biological probes. PMID- 24234771 TI - Quenching of perylene fluorescence by Co(2+) ions in dipalmitoylphosphatidylcholine (DPPC) vesicles. AB - We report the fluorescence quenching of perylene by CoCl2.6H2O in small unilamellar DPPC vesicles via energy transfer. At the probe-to-lipid ratio of 1?200 and quencher to lipid ratios of >=12.5?1, donor-donor energy transfer between clustered perylene molecules was observed as well as energy transfer from the perylene molecules to cobalt ions bothabove andbelow the main phase transition temperature of the lipid. The fluorescence quenching of perylene by CoCl2.6H2O in the lipid gel state is shown to be well described by Forster long range energy transfer when both donor-donor and donor-acceptor energy transfer are considered. In the liquid crystalline phase diffusion of the molecules is described as well as energy transfer. The interaction radiusR 0 for energy transfer from perylene to Co(2+) is found to be ~13.4+/-1.1 A in the gel phase at 303 K, in good agreement with the theoretical value forR 0 of 13.9 A. In the liquid crystalline phase at 323 K the lower value obtained forR 0, ~11.3+/-1.6 A, is attributed to saturation of the Co(2+) ions at the interfacial region of the bilayer. A diffusion coefficient of (1.06+/-0.15)*10(-6) cm(2) s(-1) is obtained for perylene-cobalt diffusion in the liquid crystalline phase at 323K. PMID- 24234772 TI - Light quenching of tetraphenylbutadiene fluorescence observed during two-photon excitation. AB - We observed the steady-state and time-resolved emission of tetraphenylbutadiene (TPB) whea excited by simultaneous absorption of two photons (514 to 610 nm). The intensity initially increased quadratically with laser power, as expected for a two-photon process. At higher laser powers the intensity increases in TPB were subquadratic. The intensity and anisotropy decay times of TPB were unchanged under the locally intense illumination. Importantly, the time zero anisotropy of TPB was decreased under conditions where the intensity was subquadratic. Furthermore, the subquadratic dependence on incident power was not observed for two-photon excitation of 2,5-diphenyloxazole (PPO), for which the incident wavelength does not overlap with the emission spectrum. These results are consistent with stimulated emission (light quenching) of TPB at high laser intensities. The phenomenon of light quenching may be important for other fluorophores used in biochemical research, particularly for the high local intensities used for two-photon excitation. PMID- 24234773 TI - The influence of rotational depolarization on the mechanism of energy transport in two-component systems: The nature of correlations. AB - The correlation effect in two-component systems of different viscosities was analyzed based on a concentration depolarization experiment. The inclusion of a correlation effect was found to be fully justified only in systems for which the localization time, taul, is considerably shorter than that of the rotational relaxation, taurot. On the grounds of an approximate analysis, taking into account the competition between the concentration and the rotational depolarization, it was possible to explain the concentration changes in the emission anisotropy in the systems investigated. PMID- 24234774 TI - Review of fluorescence anisotropy decay analysis by frequency-domain fluorescence spectroscopy. AB - This didactic paper summarizes the mathematical expressions needed for analysis of fluorescence anisotropy decays from polarized frequency-domain fluorescence data. The observed values are the phase angle difference between the polarized components of the emission and the modulated anisotropy, which is the ratio of the polarized and amplitude-modulated components of the emission. This procedure requires a separate measurement of the intensity decay of the total emission. The expressions are suitable for any number of exponential components in both the intensity decay and the anisotropy decay. The formalism is generalized for global analysis of anisotropy decays measured at different excitation wavelengths and for different intensity decay times as the result of quenching. Additionally, we describe the expressions required for associated anisotropy decays, that is, anisotropy decays where each correlation time is associated with a decay time present in the anisotropy decay. And finally, we present expressions appropriate for distributions of correlation times. This article should serve as a reference for researchers using frequency-domain fluorometry. PMID- 24234777 TI - Serum SPARC and matrix metalloproteinase-2 and metalloproteinase-9 concentrations after bariatric surgery in obese adults. AB - BACKGROUND: Remodeling of the extracellular matrix (ECM) of adipose tissue is regarded as part of the pathophysiology of obesity. Secreted protein acidic and rich in cysteine (SPARC) was the first ECM protein described in adipose tissue. Matrix metalloproteinases (MMPs) also play a role in ECM remodeling, and MMP-2 and MMP-9 may be associated with abnormal ECM metabolism. Here, we investigated changes in serum SPARC, MMP-2, and MMP-9 concentrations after bariatric surgery in obese adults. METHODS: We recruited 34 obese patients who were scheduled to undergo bariatric surgery for weight loss. We analyzed changes in serum SPARC, MMP-2, and MMP-9 concentrations before and 9 months after bariatric surgery and any associations between changes in SPARC, MMP-2, and MMP-9 concentrations and obesity-related parameters. RESULTS: Serum leptin levels significantly decreased, and the serum adiponectin level significantly increased after bariatric surgery. The serum SPARC concentration decreased significantly from 165.0 +/- 18.2 to 68.7 +/- 6.7 ng/mL (p < 0.001), and the MMP-2 concentration also decreased significantly from 262.2 +/- 15.2 to 235.9 +/- 10.5 ng/mL (p < 0.001). Changes in the serum SPARC concentration were significantly correlated with HOMA-IR changes, and changes in the serum MMP-9 concentration were found to inversely correlate with serum adiponectin changes. CONCLUSION: These findings show that significant decreases in serum SPARC and MMP-2 concentrations occur after bariatric surgery. Our results thus suggest that weight loss via bariatric surgery could alter the ECM environment, and that these changes are related to certain metabolic changes. PMID- 24234778 TI - Medication use following bariatric surgery: factors associated with early discontinuation. AB - BACKGROUND: Medication discontinuation is a common result of bariatric surgery. The influence of individual patient characteristics and surgical outcomes on overall and specific medication discontinuation is not well understood. The purpose of the current study was to assess changes in medication use and identify individual characteristics and surgical outcomes associated with medication discontinuation among bariatric patients. METHODS: The patients included in the current study received bariatric surgery from the Northern Colorado Surgical Associates of Fort Collins, Colorado, USA, between October 2007 and September 2010. Demographic, weight, health, and medication data from 400 patients with at least one 6- or 12-month post-operative appointment were extracted from the Bariatric Outcome Longitudinal Database. Multivariate regression analyses were used to investigate how patient factors affect total medication use over time, use of medications grouped by co-morbidity post-operatively, and use of specific medication classes post-operatively. RESULTS: Baseline co-morbidities, particularly type 2 diabetes,male sex, and Roux-en-Y gastric bypass surgery were significantly associated with decreased total medication use following surgery.Weight loss, systemic disease, sex, baseline co-morbidities, surgical complications, and race were significantly associated with continued use of specific medications following surgery. CONCLUSIONS: Bariatric surgery can help patients with certain characteristics discontinue medications but is not effective for all patients. Baseline health, sex, race, bariatric procedure,surgical complications, and post-operative weight loss may affect how bariatric patients' medication use changes preoperatively to post-operatively. PMID- 24234779 TI - Pathological gambling: Clinical issues, Part I. PMID- 24234780 TI - Practical issues and the assessment of pathological gamblers in a private practice setting. AB - With increased awareness and knowledge of pathological gambling comes the opportunity to share various perspectives and emerging skills. Descriptions of the assessment and treatment of the pathological gambler, spouse, and family have mushroomed in the past twenty years. However, most treatment summaries have come out of institutional or government funded settings. This article discusses various practical aspects of working with pathological gamblers in an outpatient, fee for service private practice setting. The author also describes refinements made in the assessment process since he first began working with pathological gamblers in 1979. PMID- 24234781 TI - A psychodynamic approach to the treatment of pathological gambling: Part I. Achieving abstinence. AB - A psychodynamic approach emphasizes the meaning and consequences of one's behavior. After a brief review of the literature, the authors present the first of a two-part model for psychodynamic psychotherapy with pathological gamblers. In this first phase, the immediate goal is abstinence, and five strategies for obtaining it are discussed. These consist of 1.) breaking through the denial 2.) confronting omnipotent defenses 3.) interrupting the chasing cycle 4.) identifying reasons for gambling, and 5.) motivating the patient to become an active participant in treatment. An argument is made for integrating a traditional psychodynamic approach with an addictions model. PMID- 24234782 TI - Transference and countertransference reactions in the psychotherapy of pathological gamblers. AB - Traditionally, in psychodynamic forms of treatment, the patient's relationship with the therapist is central to eliciting and exploring the patient's characteristic ways of thinking, feeling and behaving. Research has increasingly demonstrated the significance of the therapeutic relationship to the treatment outcome. Since little has been written about the therapist-patient relationship in the treatment of pathological gambling, we shall describe what we have found to be some of the common and problematic transference and countertransference reactions and interactions. Both positive and negative transferences and countertransferences will be discussed not only as obstacles to successful therapy, but as tools for understanding patients' conflicts, defenses and reasons for gambling. PMID- 24234783 TI - Compulsive gambling: Structured family intervention. AB - Family intervention has been an effective procedure for getting alcoholics into treatment for more than twenty years. Now this technique is being used with compulsive gamblers. Because the gambling disorder is so easy to hide, the patient seems to be further into the illness by the time the family seeks help. Furthermore, because the gambling offers intermittent rewards, the denial in both the patient and family appears to be stronger than found with most alcoholics.During the intervention it is important to tell the compulsive gambler why the help of a professional was sought; what changes have been observed by family members and friends as a result of his/her gambling; how family relationships have been affected; what is feared will happen if he/she doesn't get help; and what each family member hopes will happen once the gambler is in recovery.Most concerned persons enter family interventions with the sole purpose of getting the gambler into treatment. However, since this is a family disease, ethically the primary goal of family intervention needs to be to getsomeone into treatment, if not the individual suffering with the disease then one or more of those concerned persons suffering from it. PMID- 24234784 TI - The importance of coping skill enhancement in the treatment of the pathological gambler. AB - The importance of coping skill enhancement in the treatment of pathological gamblers is discussed. It is particularly critical to assess and enhance the coping skills of relapse prone gamblers who are marked by unusual degrees of impulsivity, high levels of negative affect and feelings of helplessness and hopelessness. A study of 1129 substance abusers, including 140 with serious gambling problems is reported. All were assessed to determine their repertoire of coping skills. The patients with serious gambling problems utilized significantly more avoidant and impulsive coping styles. PMID- 24234785 TI - Pathological gambling and switching addictions: Report of a case. AB - The phenomenon of "switching addictions," defined as a substitution of one chemical or behavioral addiction pattern for another, has been observed in clinical practices for some time. This case study describes a patient who, in attaining abstinence from alcohol and other drug dependence, became a pathological gambler. The complexities of personal history, medical history and psychiatric history are described as well problems in treatment. PMID- 24234786 TI - Utility of N-peracetylation of proteins for their structure determination by mass spectrometry. AB - Acetylation of the animo groups (N-terminus and lysine) of proteins before enzymatic or chemical cleavage was explored as an approach to provide additional information in the course of the determination of amino acid sequences. The major advantage is the ability to differentiate glutamine from lysine, because only the latter is acetylated and thus increases in mass by 42 Da. Horse heart cytochrome c could be fully N-actetylated and even on prolonged digestion with chymotrypsin underwent very little tryptic cleavage, in contrast to the native protein where this side reaction is extensive. Sperm whale myoglobin is more difficult to acetylate, but even at 40%-50% average acetylation, all 19 lysines could be identified unambiguously. A proteolytic digest of acetylated protein is thus a useful component of strategies for the determination of the primary structure of proteins by tandem mass spectrometry. PMID- 24234787 TI - Functional group-selective ion-molecule reactions of ethylene glycol and its monomethyl and dimethyl ethers. AB - The selective methylation and methylene substitution reactions of dimethyl ether ions with ethylene glycol, ethylene glycol monomethyl ether, and ethylene glycol dimethyl ether were investigated in a quadrupole ion trap mass spectrometer. Whereas the reactions of ethylene glycol and ethylene glycol monomethyl ether with the methoxymethylene cation 45(+) gave only [M + 13](+) product ions, the reaction of ethylene glycol dimethyl ether with the same reagent ion yielded exclusively [M + 15](+) ions. The relative rates of formation of these products and those from competing reactions were examined and rationalized on the basis of structural and electronic considerations. The heats of formation for various relevant species were estimated by computational methods and showed that the reactions leading to the [M + 13](+) ions were more energetically favorable than those leading to the [M + 15](+) products for cases in which both reactions are possible. Finally, the collision-induced dissociation behavior of the [M + H](+), [M + 13](+), and [M + 15](+) ions indicated that the and [M + H](+) rons dissociated by analogous pathways and were thus structurally similar, whereas the [M + 13](+) ions possessed distinctly different structural characteristics. PMID- 24234788 TI - Fe(+) chemical ionization of peptides. AB - Laser-desorbed peptide neutral molecules were allowed to react with Fe(+) in a Fourier transform mass spectrometer, using the technique of laser desorption/chemical ionization. The Fe(+) ions are formed by laser ablation of a steel target, as well as by dissociative charge-exchange ionization of ferrocene with Ne(+). Prior to reaction with laser-desorbed peptide molecules, Fe(+) ions undergo 20-100 thermalizin collisions with xenon to reduce the population of excited-state metal ion species. The Fe(+) ions that have not experienced thermalizing collisions undergo charge exchange with peptide molecules. Iron ions that undergo thermalizing collisions before they are allowed to react with peptides are found to undergo charge exchange and to form adduct species [M + Fe(+)] and fragment ions that result from the loss of small, stable molecules, such as H2O, CO, and CO2, from the metal ion-peptide complex. PMID- 24234789 TI - Ion-molecule reactions in mixtures of trimethylaluminum and methylamines. AB - The ion-molecule reactions of mixtures of trimethylaluminum and methylamines, to serve as a model system for group 13-15 semiconductor fabrication, were examined by using Fourier transform ion cyclotron resonance mass spectrometry. Sequential ion-molecule reactions leading to formation of multiple adduets were observed for each of the reactant mixtures investigated. Collision-induced dissociation was used to probe the adduct structures. There is evidence for hydrogen bonding between the amines and aluminum in most of the adducts studied. Rearrangement of the aluminum/nitrogen skeletons was not observed, although the aluminum/nitrogen bonds appear to be relatively strong, so that stable adducts can be formed. The monomethylamine and dimethylamine readily produce gas-phase neutral adducts with trimethylaluminum, which can be related to the basicities of the methylamines. PMID- 24234790 TI - CH2 (+) transfer to pyridine nucleophiles: a means of producing alpha-distonic ions. AB - The distonic radical cation C5H5N(+)-(.)CH2 can be generated by the reactions of neutral pyridine with the radical cations of cyclopropane, ethylene oxide, and ketene, as well as with the [C3H6](+) ion from fragmentation of tetrahydrofuran. The distonic product ion can be distinguished from isomeric methylpyridine radical cations because the former gives characteristic [M-CH2](+), [M - CH2NCH](+), and a doubly charged ion, all of which are produced on collisional activation. Furthermore, the distonic species completely transfers CH2 (+) to more nucleophilic, substituted pyridines. These properties are all consistent with the assigned distonic structure. Another distonic isomer, the (3-methylene) pyridinium ion, can be distinguished from the (1-methylene)pyridinium ion on the basis of their different fragmentation behaviors. The latter ion exhibits higher stability (lower reactivity) than the prototypal [.CH2NH3 (+)], making available a distonic species whose bimolecular reactivity can be readily investigated. PMID- 24234791 TI - Multiple-stage mass spectrometry in structural characterization of organophosphorus compounds. AB - Multiple-stage mass spectrometry involving consecutive collision-activated dissociation reactions was used to examine the structures of fragment ions commonly formed on electron ionization of organophosphorus esters. The compounds studied include several aryl thiophosphates, some of which are analogs of common pesticides. Energy-resolved collisionactivated dissociation experiments allow the dissociation of the molecular ions of these compounds in such a manner that only a few fragment ions dominate the spectrum. An abundant fragment ion of m/z 109, formed from all of the compounds studied, can have at least four different stable structures: (CH3O)2PO(+), CH3CH2OP(O)OH(+), CH2 =CHOP(H)(OH)2 (+), and (CH2O)2P(H)OH(+). The structure of the fragment ion of m/z 109 was found to reflect the phosphorus-containing part of the compounds studied. Another abundant fragment ion obtained for all the aryl esters studied is structurally characteristic of the aromatic moiety of the molecule. This fragment ion is the result of a complex rearrangement involving transfer of an alkylene group to the aromatic ring from the phosphoruscontaining part of the molecular ion. The utility of these fragment ions in the structural characterization of unknown organophosphorus esters is discussed. PMID- 24234792 TI - Collision-induced and infrared multiphoton dissociation studies on M(acetone)2 (+) (M=Al, Fe, Co, Cu, ScO) in the gas phase. AB - In this paper we report an extension of our earlier study on the structure of Alfacetone)2 (+) Collision-induced dissociation (CID) on MfacetoneXacetone-d6)(+) for M = Al, Fe, Co, and Cu yields primarily, if not exclusively, nearly equal amounts of acetone and acetone-d6. Likewise, infrared multiphoton dissociation (IRMPD) at 10.6 MUm yields, exclusively, nearly equal losses of the labeled and unlabeled acetones. These results suggest that the two acetone ligands bind in an equivalent fashion. Sc(+) was also studied, which proved to be the most interesting. Sc(+) reacts with acetone to form primarily ScO(+), which undergoes higher order reactions leading to several products including ScO(acetone)2 (+). IRMPD on this ion produces ScO(acetone-d6)(CD2CO)(+), while its perdeuterated analog also produces ScO(acetone-d6)(+) in addition to ScO(acetone-d6(CD2CO)(+). The IRMPD results are supplemented by studying the primary and higher order reactions of Sc(+) with acetone, as well as the CID of ScO(acetone)2 (+). Finally, a qualitative assessment of the infrared photodissociation cross sections is given. It is found that the relative photodissociation cross sections follow the orders Co(acetone-d6)2 (+) > Co(acetone)(acetone-d6) > Co(acetone)2 (+) and Co(acetone-d6)(+) > Co(acetone)(+). PMID- 24234793 TI - Energy deposition during electron-induced dissociation. AB - We report studies of the internal energy deposited during activation of mass selected ions through electron-ion collisions. Characteristic fragmentations of the molecular ion of limonene and W(CO) (n/+) (n = 1-6) indicate that electron induced dissociation in a Fourier transform ion cyclotron resonance mass spectrometer proceeds via multiple collisions and that the average internal energy deposited during the activation process can be selected to be similar to that associated with electron-impact ionization. Control of the degree of ion excitation through selection of the electron energy, flux, and interaction time with the ions of interest is demonstrated, and advantages of this promising activation technique are discussed. PMID- 24234794 TI - Triple quadrupole mass spectrometry as applied to flame diagnostics: study of the C2H 4/N 2O/Ar flame. AB - A recently developed research apparatus for characterization of low-pressure premixed flames has been developed and was used to characterize the C2H4/N2O/Ar flame at 20 torr. This instrument incorporates several diagnostic techniques in one apparatus so that individual techniques can be quantitatively compared and the usable detection range (both in terms of resolution and species detection) expanded. Results discussed in this report include mass analysis by triple quadrupole mass spectrometer and temperature measurement by thermocouple. Concentration profiles in the one-dimensional flame include CO, N2, and C2H4, at nominal m/z 28 as well as CO2 and N2O at m/z 44. PMID- 24234795 TI - Competitive ionization of tetraphenylporphyrin in a laser-generated metal ion plasma. AB - The ionization of tetraphenylporphyrin (TPP) in a laser-desorbed metal ion plasma is examined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Competitive reaction pathways observed to generate abundant molecular ion species include electron detachment, cation attachment, charge exchange, metallation, and transmetallation in the positive ion mode and electron capture, metallation, and transmetallation in the negative ion mode. In general, cation attachment reactions dominate positive ion spectra below the laser irradiance threshold for plasma ignition, although the metallation product from [TPP](+) reaction with the metal atom, M, is observed. Negative ion products are not observed in the FT-ICR spectrum when a plasma is not formed. Under plasma ignition conditions, positive ion spectra include [TPP](+) formed by charge exchange with M(+), which is also present in the spectrum. Negative ion spectra are dominated by [TPP](-); which is formed by attachment to thermal electrons generated in the plasma. Metallation reactions involving TPP and the metal substrate are examined. Positive ion metallation products are observed both in the absence of a plasma through reaction of [TPP](+) with M and by a second pathway under plasma ignition conditions through reaction of TPP with M(+). In negative ion mode, metallation is only observed under plasma ignition conditions through reaction of [TPP](-) with M. Observation of metallated products is found to be consistent with formation of stable metal oxidation states in the metallated porphyrin. PMID- 24234796 TI - Concentric tube vacuum chamber for high magnetic field, high-pressure ionization in a fourier transform ion cyclotron resonance mass spectrometer. AB - A new differential pumping design for external source Fourier transform ion cyclotron resonance mass spectrometry is described. A network of concentric tubes of increasing diameter terminates at a series of conductance limits across which a pressure from atmosphere to low-10(-8) torr is achieved. This design permits high-pressure sources to be positioned within the solenoidal superconducting magnet less than 20 cm from the analyzer trapped ion cell. Ionization at high magnetic field offers the advantage of radial ion confinement and consequently delivers enhanced ion current to the trapped ion cell. Ion injection utilizing this vacuum chamber design is simpler than previously reported serial pumping stage designs because elaborate focusing optics to overcome the magnetic mirror effect are unnecessary. Two probe-mounted atmospheric pressure sources are described as evidence of the general applicability of the concentric tube vacuum chamber. An electrospray source that delivers several hundred picoamperes of ion current to the cell yields high-sensitivity spectra of proteins beyond 100 kDa. Improved pumping compared with a prototype concentric tube network configuration now permits mass resolution in excess of 20,000 for the [M + 4H](4+) ion of melittin. The resolution is sufficient to distinguish isotope peaks within a single charge state. A probe-mounted, pulsed-laser ablation source that permits cluster formation in the strong magnetic field is also demonstrated. PMID- 24234797 TI - High-frequency fourier transform ion cyclotron resonance mass spectrometry. AB - The experimental Fourier transform ion cyclotron resonance (FT/ICR) frequency range has been extended to 107 MHz. We report the observation of FT/ICR signals from electron-ionized species of mass-to-charge ratio 8, 7, 6, 5, 4, 3, 2, and 1 MU per elementary charge. We show that moderately high charge states of atomic ions (e.g., N(3+)) are easily generated and detected. Several applications for high-frequency FT/ICR mass spectrometry are proposed and discussed. PMID- 24234798 TI - Two thermospray probe insert designs that allow clogged probes to be rapidly replaced. AB - Thermospray has been widely accepted as a reliable technique for the analytical scientist. Many manufacturers provide thermospray as an option on their mass spectrometers. One difficulty experienced with thermospray is the clogging of the probe inserts. This report describes two new probe insert designs that minimize the problems associated with clogged probe inserts. Both of these new designs minimize the expense and downtime associated with clogged probe inserts. The capillary can be easily and quickly replaced to ensure optimum performance. The new fused-silica probe insert design that is described worked. adequately; there was, however, some beam instability caused by rapid oscillation of the fused silica tubing near the tip. This oscillation also caused the tip to become brittle, necessitating frequent replacement. The stainless steel probe insert described did not exhibit these problems. Last, a comparison is made between the two new designs and the standard Kratos thermospray probe insert. PMID- 24234799 TI - Ion cloud manipulation using the radiofrequency-only-mode as an improvement for high mass detection in fourier transform mass spectrometry. AB - It has been difficult to achieve the expected high resolving power for high-mass biomolecule ions in Fourier transform mass spectrometry. Our hypothesis is that ion clouds produced by laser desorption or injection are diffuse and produce poor signals. To test the hypothesis, clouds of benzene molecular ions produced by electron ionization were purposefully expanded via magnetron mode excitation and characterized by a new experimental sequence for cloud sectional analysis. The expanded cloud was then successfully focused to the trap center by using a high pressure dynamic event (radiofrequency-only mode). The expanded cloud in a conventional cubic trap produces no detectable signal, whereas the focused cloud in a compensated trap yields a high-resolution signal with good signal-to-noise ratio. PMID- 24234800 TI - Improved fourier-transform ion-cyclotron-resonance mass spectrometry of large biomolecules. AB - Initial results from a Fourier-transform mass spectrometer with a 6.2 Tesla magnet using electrospray ionization show substantial improvements in resolution, mass accuracy, mass range, signal/noise, and tandem mass spectromehy capabilities compared to our earlier 2.8 T instrument that demonstrated the first unit resolution mass spectra of molecules as large as myoglobin (17 kDa). The new instrument exhibits greater than 10(6) and 10(5) resolving power for 8.6 and 29 kDa, respectively, proteins. Using an internal standard, the mass measuring error for myoglobin is less than 1 ppm. Nozzle-skimmer dissociation during electrospray of carbonic anhydrase (29 kDa) has yielded 38 fragment ions for which both mass and charge are identifiable; of these, 21 have been assigned to expected oligopeptide fragments. PMID- 24234802 TI - Conference report. PMID- 24234803 TI - Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems. AB - Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA PEGPLGA and alpha-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined. PMID- 24234804 TI - Altered functional connectivity of the default mode network in diffuse gliomas measured with pseudo-resting state fMRI. AB - The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III-IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity. PMID- 24234806 TI - Does the workers' compensation system think multidimensionally? PMID- 24234807 TI - Factors influencing the cost of chronic low back injuries: An analysis of data from independent medical examinations. AB - Cost factors were examined in 157 patients with work- related spine injuries who were referred to a second opinion program between 1985 and 1991. The independent medical examination (IME) included a history, physical examination, and review of imaging and other studies. Data on demographic variables, litigation, work, injury history, physical examination, and imaging studies were recorded. A standard measure of psychological status (Low Back Pain Symptom Check List) was filled out. The instrument uses pain language as a clinical marker of psychological disturbance linked to a range of conflictual issues such as suppressed anger, burdensome feeling of inferiority, damaged self- esteem, role confusion, abnormal mentation, fear of responsibility or intimacy, gender issues, sexual concerns, disturbing arousal, and the like. Since it relies exclusively on pain language for diagnosis, it does not identify the specific nature of the psychological conflict. Data on treatment, final resolution, and cost were obtained from computerized files of the insurance company. The total cost incurred was $6,551,139. This averaged to $41,727 per case. More expensive cases were associated with a surgical intervention, psychological disturbance, litigation, motor weakness, and positive radiographs. These five variables accounted for 48% of the cost variance. Surgery accounted for 19.9% of the variance and contained the most expensive cases ($68,310 vs. $31,423). Psychological disturbance was detected in 27% of the sample and accounted for 10.5% of the cost variance. Litigation was present in 72% of the cases and accounted for 9.1% of the cost variance. Motor strength and radiographs taken together accounted for 8.4% of the variance. The usefulness of this information was explored from an actuarial and medical perspective. PMID- 24234805 TI - Recommendations to prescribe in complex older adults: results of the CRIteria to assess appropriate Medication use among Elderly complex patients (CRIME) project. AB - The occurrence of several geriatric conditions may influence the efficacy and limit the use of drugs prescribed to treat chronic conditions. Functional and cognitive impairment, geriatric syndromes (i.e. falls or malnutrition) and limited life expectancy are common features of old age, which may limit the efficacy of pharmacological treatments and question the appropriateness of treatment. However, the assessment of these geriatric conditions is rarely incorporated into clinical trials and treatment guidelines. The CRIME (CRIteria to assess appropriate Medication use among Elderly complex patients) project is aimed at producing recommendations to guide pharmacologic prescription in older complex patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes, and providing physicians with a tool to improve the quality of prescribing, independent of setting and nationality. To achieve these aims, we performed the following: (i) Existing disease-specific guidelines on pharmacological prescription for the treatment of diabetes, hypertension, congestive heart failure, atrial fibrillation and coronary heart disease were reviewed to assess whether they include specific indications for complex patients; (ii) a literature search was performed to identify relevant articles assessing the pharmacological treatment of complex patients; (iii) A total of 19 new recommendations were developed based on the results of the literature search and expert consensus. In conclusion, the new recommendations evaluate the appropriateness of pharmacological prescription in older complex patients, translating the recommendations of clinical guidelines to patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes. These recommendations cannot represent substitutes for careful clinical consideration and deliberation by physicians; the recommendations are not meant to replace existing clinical guidelines, but they may be used to help physicians in the prescribing process. PMID- 24234808 TI - Economic impact of ergonomic intervention-Four case studies. AB - The economy of ergonomic improvements is reported as case studies from four Swedish companies. Poor workplace ergonomics and related musculoskeletal problems were already known and had caused repeated sick- leave periods at these workplaces. Expenses associated with certain preventive activities were accounted for and financial effects were estimated based on interviews with representatives at the companies. When costs were compared to gains, the improvements appeared to be highly profitable. PMID- 24234809 TI - A quantitative description of typing biomechanics. AB - One approach to combating work- related upper extremity musculoskeletal disorders (UEMSDs) is to improve understanding of MSD risk factors through quantitative biomechanical characterization of manual tasks, including joint postures, joint dynamics, and force exertion. This paper describes a methodology employed to quantitatively assess professional typing in a workplace setting, and the results of that assessment. Results are compared between different kinds of typing tasks, and between typing and hand- intensive industrial tasks, based on nontask- specific biomechanical terms. Quantitative, biomechanical characterizations of manual tasks will lead to identification of appropriate ranges for joint kinematics and force exertion, which will, in turn, facilitate proper design of manual tasks. Additionally, the methodology could be used to assess manual performance of skilled tasks for proper (healthy) technique, or be used to evaluate progress through a course of rehabilitation (when do an impaired worker's motions begin to resemble motions of healthy workers?). PMID- 24234810 TI - Relationships among grip strength, work capacity, and recovery. AB - The relationship between strength, fatigue, and work capacity is a central issue for occupational rehabilitation. Musculoskeletal impairments often are expressed functionally as a loss of strength. For work tasks that require strength, such impairments may have a detrimental effect on work capacity that is sufficient to be disabling. How important is strength as a component of work capacity? How do work capacity and strength affect recovery time from repetitive forceful upper extremity work ? A sample of 40 healthy subjects comprised of 20 males and 20 females was studied in a model that used the isotonic strength of each subject to set exercise levels for subsequent forceful repetitive gripping tasks. Resistance levels of 75%, 50%, and 25% of maximum were used for one-per-second repetitions until the subject could not maintain that pace. Isometric grip strength was measured after 1 minute of rest and after 5, 10, and 20 minutes. Results indicate that males and females do not differ in terms of their rate of recovery and that the best predictor of recovery time is the immediate measurement of strength loss following cessation of work activity. PMID- 24234812 TI - Strategies for enhancing occupationally-oriented rehabilitation. PMID- 24234811 TI - Muscular fatigue patterning in power grip assessment. AB - Physical fatigue has been identified as a risk factor associated with the onset of occupational injury. Muscular fatigue developed from repetitive hand-gripping tasks is of particular concern. This study examined the use of a maximal, repetitive, static power grip test of strength-endurance in detecting differences in exertions between workers with uninjured and injured hands, and workers who were asked to provide insincere exertions. The main dependent variable of interest was power grip muscular force measured with a force strain gauge. Group data showed that the power grip protocol, used in this study, provided a valid and reliable estimate of wrist-hand strength-endurance. Force fatigue curves showed both linear and curvilinear effects among the study groups. An endurance index based on force decrement during repetitive power grip was shown to differentiate between uninjured, injured, and insincere groups. PMID- 24234813 TI - Differential expression profile of membrane proteins in Aplysia pleural-pedal ganglia under the stress of methyl parathion. AB - This study was aimed to analyze the alteration of membrane protein profiles in Aplysia juliana Quoy & Gaimard (A. juliana) pleural-pedal ganglia under MP exposure. Both the results of GC-MS analysis and the activity assay of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) reveal that MP toxicological effects on Aplysia left and right pleural-pedal ganglia are different under 7 and 14 days of exposure. Therefore, Aplysia were subjected for exposure at two concentrations (1 and 2 mg/l) of MP for 7 and 14 days for membrane proteomic study. As a result, 19 and 14 protein spots were differentially expressed in A. juliana left pleural-pedal ganglia under 7 and 14 days treatment, and 20 and 14 protein spots found with differential expressions in their right ganglia under the same treatment, respectively. Several proteins with expression variations were detected from both the left and right pleural pedal ganglia; however, most proteins have distinctive expressions, indicating different mechanisms might be involved in initiating MP toxicology in left and right ganglia. Among the total differential protein spots obtained, 29 proteins were classed as membrane proteins. These proteins are mainly involved in the metabolism process, cell redox homeostasis, signal transduction, immunology, intracellular transport and catalysis, indicating MP toxicity in mollusks seems to be complex and diverse. Some differentially expressed proteins were further confirmed by Western blotting and quantitative real-time PCR. These results might provide renovated insights to reveal the mechanism of MP-induced neurotoxicity, and the novel candidate biomarkers might have potential application for environmental evaluation of MP pollution level. PMID- 24234814 TI - Remanence of lead pollution in an urban river system: a multi-scale temporal and spatial study in the Seine River basin, France. AB - Total lead (Pb) concentration and Pb isotopic ratio ((206)Pb/(20)7Pb) were determined in 140 samples from the Seine River basin (France), covering a period of time from 1945 to 2011 and including bed sediments (bulk and size fractionated samples), suspended particulate matter (SPM), sediment cores, and combined sewer overflow (CSO) particulate matter to constrain the spatial and temporal variability of the lead sources at the scale of the contaminated Seine River basin. A focus on the Orge River subcatchment, which exhibits a contrasted land use pattern, allows documenting the relation between hydrodynamics, urbanization, and contamination sources. The study reveals that the Pb contamination due to leaded gasoline that peaked in the 1980s has a very limited impact in the river nowadays. In the upstream Seine River, the isotopic ratio analysis suggests a pervasive contamination which origin (coal combustion and/or gasoline lead) should be clarified. The current SPM contamination trend follows the urbanization/industrialization spatial trend. Downstream of Paris, the lead from historical use originating from the Rio Tinto mine, Spain ((206)Pb/(207)Pb=1.1634 +/- 0.0001) is the major Pb source. The analysis of the bed sediments (bulk and grain size fractionated) highlights the diversity of the anthropogenic lead sources in relation with the diversity of the human activities that occurred in this basin over the years. The "urban" source, defined by waste waters including the CSO samples ((206)Pb/(207)Pb=1.157 +/- 0.003), results of a thorough mixing of leaded gasoline with "historical" lead over the years. Finally, a contamination mixing scheme related to hydrodynamics is proposed. PMID- 24234815 TI - Rhodamine B induces long nucleoplasmic bridges and other nuclear anomalies in Allium cepa root tip cells. AB - The cytogenetic toxicity of rhodamine B on root tip cells of Allium cepa was investigated. A. cepa were cultured in water (negative control), 10 ppm methyl methanesulfonate (positive control), and three concentrations of rhodamine B (200, 100, and 50 ppm) for 7 days. Rhodamine B inhibited mitotic activity; increased nuclear anomalies, including micronuclei, nuclear buds, and bridged nuclei; and induced oxidative stress in A. cepa root tissues. Furthermore, a substantial amount of long nucleoplasmic bridges were entangled together, and some nuclei were simultaneously linked to several other nuclei and to nuclear buds with nucleoplasmic bridges in rhodamine B-treated cells. In conclusion, rhodamine B induced cytogenetic effects in A. cepa root tip cells, which suggests that the A. cepa root is an ideal model system for detecting cellular interactions. PMID- 24234816 TI - MRI and neuropathological validations of the involvement of air pollutants in cortical selective neuronal loss. AB - Vehicles are a major source of air pollution, especially particulate matter (PM) pollution, throughout the world and auto-rickshaws are considered main contributors to this air pollution. PM, in addition to causing respiratory and cardiovascular disorders, has potential to gain access to the brain and could induce neuroinflammation leading to different neurological disorders. Therefore, in the current project, MRI and immunohistochemistry techniques were adopted to ascertain the neurotoxic potential of the chronic exposure to different PM generated by two-stroke auto-rickshaws (TSA), four-stroke auto-rickshaws (FSA), and aluminum sulfate (AS) solution in rats. The results highlighted that all treated groups followed a pattern of dose-dependent increase in pure cortical neuronal loss, selective neuronal loss (SNL), nuclear pyknosis, karyolysis, and karyorrhexis. Mild to moderate areas of penumbra were also observed with increase in the population of activated microglia and astrocytes, while no alteration in the intensities of T2W MRI signals was perceived in any group. When comparing the findings, TSA possess more neurotoxic potential than FSA and AS, which could be associated with increased concentration of certain elements in TSA emissions. The study concludes that chronic exposure to PM from TSA, FSA, and AS solutions produces diverse neuropathies in the brain, which may lead to different life threatening neurological disorders like stroke, Alzheimer's, and Parkinson's disorders. Government and environmental agencies should take serious notice of this alarming situation, and immediate steps should be implemented to improve the standards of PM emissions from auto-rickshaws. PMID- 24234819 TI - Detecting enzymes in living cells using fluorogenic substrates. AB - Characteristics of fluorogenic substrates designed for detection of enzyme activity in living cells are reviewed. Improved retention of the fluorescent products in the cell of origin can be achieved by structural modifications to the substrate that result in association with membrane lipids or conjugation to intracellular glutathione. Newly-developed substrates that yield fluorescent precipitates provide the additional advantage of allowing subcellular localization of sites of enzymatic activity. Improved detection sensitivity can also be achieved by targeted delivery of substrates for processing by specific organelles. Substrates designed for monitoring oxidative activity and lipid metabolism provide examples of this approach. PMID- 24234817 TI - Stem cell regeneration of degenerated intervertebral discs: current status (update). AB - Low back pain, strongly associated with intervertebral disc (IVD) degeneration, affects a large proportion of the population and has major social and economic costs. Current treatments remain inadequate, targeting the symptoms without addressing the underlying cause. As such, efforts are being directed towards development of therapies aimed at alleviating pain through the restoration of IVD function. The potential of cell-based therapies for the treatment of IVD degeneration are being actively explored, with an emphasis on cell/biomaterial tissue engineering. Adult mesenchymal stem cells, capable of differentiating down the discogenic lineage, have shown promise as a suitable cell source for IVD tissue engineering. However, a number of factors, (discussed in this review), remain to be addressed, including development of a differentiation protocol to produce the correct cell phenotype, identification of suitable biomaterials for cell delivery/implantation, and ensuring cell survival and correct function upon implantation into the degenerate IVD. PMID- 24234820 TI - Use of Nile Red as a long-wavelength fluorophore in dual-probe studies of ligand protein interactions. AB - The long-wavelength fluorescence probe, Nile Red, has polarity-dependent fluorescence intensity and wavelength properties that can be used to monitor the binding of drugs and other ligands to plasma proteins such as albumin and alpha-1 acid glycoprotein. This paper shows that it can be used in tandem with another fluorescence probe, 1-anilinonaphthalene-8-sulfonic acid, to study two or more types of ligand binding sites simultaneously. Some ligands displace one or the other probe from the protein/dual-probe complex, other ligands displace both probes. In each case the resulting decrease in fluorescence can be used to estimate the numbers of binding sites and their association constants. PMID- 24234818 TI - Does exercise make migraines worse and tension type headaches better? AB - Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches. PMID- 24234821 TI - New fluorescent labels for time-resolved detection of biomolecules. AB - New dyes with characteristic fluorescence lifetimes have been developed for bioanalytical applications. Based upon the concept of "multiplex dyes," we have designed rhodamine dyes with nearly identical absorption and emission spectral characteristics but different fluorescence lifetimes. Extending this principle to applications with laser diodes, new rhodamines with functional groups for covalent coupling of analytes have been developed. The new labels exhibit absortion and fluorescence beyond 600 nm and have a high quantum efficiency, even in aqueous buffer systems. PMID- 24234822 TI - A new fluorescence probe for trace metal ions: Cation-dependent spectroscopic properties. AB - The fluorescence behavior of a new bipyridyl ligand, 2,2'-bipyridyl-3,3'-diol (BPDO), was studied as a function of the metal ion complexed. At pH 7.6, the fluorescence of BPDO is strongly decreased by complexation to Cu(II), but binding to Zn(II) leads to an increase in fluorescence intensity. Time-resolved fluorescence measurements suggest that in the case of Cu(II), a nonfluorescent complex is formed, whereas in the presence of Zn(II), a new, longer decay component appears. PMID- 24234823 TI - New diphenylhexatriene derivatives as fluorescent membrane probes: Partitioning properties. AB - Three new diphenylhexatriene derivatives, two phospholipids and one single-chain amphiphilic molecule, have been synthesized and considered as probes for measuring membrane fluidity by fluorescence anisotropy. The possibility of using these probes to determine specifically fluidity of inner leaflets of cellular plasma membranes was inferred from their partitioning properties between gel and liquid crystalline phases of phospholipid vesicles of binary composition. PMID- 24234824 TI - Dipyrenylphosphatidylcholine as a probe of bilayer pressures. AB - We have used dipyrenylphosphatidylcholines (dipyPCs) to study the pressure in the fluid lamellar phase formed by mixtures of fully hydrated dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE). As we increase the DOPE mole fraction at 25 degrees C we observe a linear increase in the ratio of the excimer-to-monomer signal (E/M1). We argue that this observation can be understood in terms of an increase in the lateral pressure in the chain region, i.e., in the bilayer plane. This change itself is driven by the decrease in lateral pressure between headgroups as we add DOPE. We expect the lateral pressure to vary in magnitude as we probe the bilayer at different depths [1]. We have confirmed this by recording E/M1 using di[10-(pyren-1 yl)decanoyl]phosphatidylcholine (10dipyPC) and di[4-(pyren-1 yl)butanoyl]phosphatidylcholine (4dipyPC). We find that in 100% DOPC the E/M1 for 4dipyPC is 2.5 times greater than that for 10dipyPC. The above observations can all be rationalized in terms of changes in the lateral pressure profile. An inverse hexagonal liquid crystalline phase is found in the range 100-83% DOPE [2]. In this region of the phase diagram we observe a quadratic variation in E/M1, with a minimum at 95% DOPE. We hypothesize that this variation reflects the chain stretching that is necessitated by the geometrical packing constraints of the hexagonal phase [3]. Again, we find that the E/M1 for 4dipyPC is greater than that for 10dipyPC, but in this phase only by a factor of two. PMID- 24234825 TI - An investigation of squaraines as a new class of fluorophores with long wavelength excitation and emission. AB - We present an overview of our investigation of the spectral properties and photostabilities of squaraine derivatives. The objective was to identify long wavelength probes with reasonable quantum yields, reasonably long lifetimes, and good photostabilities for use in fluorescence-based assays and/or imaging. Both symmetrical and unsymmetrical squaraines were studied. Based on this investigation the most suitable probes for use in a biological application were found to be the symmetrical indolenine derivatives of the squaraines, which display the highest photostability. Importantly, their quantum yields and lifetimes increase significantly upon covalent and noncovalent binding to proteins (bovine serum albumin, antibodies), demonstrating the usefulness of the squaraines as long wavelength probes. The squaraine absorbance maxima between 630 and 650 nm allows the use of the new commercially available 635- and 650-nm diode lasers. PMID- 24234826 TI - Assessment of membrane potential using confocal microspectrofluorimetry. AB - Some slow potentiometric dyes, e.g., 3,3'-dipropylthiacarbocyanine and tetramethylrhodamine methyl ester, exhibit fluorescence spectral changes on redistributing from aqueous medium to cells. This effect has been used for spectroscopic discrimination of the emissions from free and bound dyes in cells. Such a discrimination can, in principle, allow for the assessment of cell membrane potential in individual cells, using the Nernst equation applied to the ratio of free dye fluorescence intensities inside and outside of the cell. PMID- 24234827 TI - Fluorescence lifetime imaging of intracellular calcium. AB - Fluorescence lifetime imaging microscopy (FLIM) is a new methodology for studying the spatial and temporal dynamics of macromolecule, molecules, and ions in living cells. In FLIM image contrast is derived from the mean fluorescence lifetime at each point in a two-dimensional image. In our case the lifetime was measured by the phase-modulation method. We describe our FLIM apparatus, which consists of a fluorescence microscope, high-speed gated proximity focused MCP image intensifier, and slow-scan CCD camera. To accomplish subnanosecond time-resolved imaging, the gain of the image intensifier is modulated with a high-frequency signal, resulting in stationary phase-sensitive intensity images on the image intensifier. These images are recorded using a cooled slow-scan CCD camera and stored in an image processor. The lifetime images are created from a series of phase-sensitive images at various phase shift of the gain-modulation signal. We demonstrate calcium concentration imaging in living COS cells based on Ca(2+) induced lifetime changes of Quin-2. The phase-angle image is mapped to the Ca(2+) concentration image using anin vitro-determined calibration curve. The Ca(2+) concentration was found to be uniform throughout the cell. In contrast, the intensity image shows significant spatial differences, which likely reflect variations in the thickness and distribution of probe within the cell. PMID- 24234828 TI - A new calibration equation for ratiometric fluorescent ion indicators: Application to fura-2. AB - The absolute values of intracellular ion concentrations as monitored by specific fluorescent indicators are determined by using calibration curves obtained underin vitro andin vivo conditions. In the derivation of the calibration curve by Grynkiewicz et al [(1985)J. Biol. Chem 260, 3440] it is implicitly assumed that the observed fluorescence signal is directly related to the concentrations of the free dye and the dye-ion complex in the ground state. We modified the calibration equation so that ion binding and dissociation in the excited state are taken into account. The extended calibration equation assumes the knowledge of the rate constants in the excited state. Expressions for the calibration curve assuming the absence or presence of an excited-state reaction are compared for the Ca(2+) indicator Fura-2. The excited-state rate constants are determined by global compartmental analysis of time-resolved fluorescence decays of Fura-2 collected at various excitation and emission wavelengths using different Ca(2+) concentrations. It is found that for Fura-2 there is negligible interference of the excited-state reaction so that the original calibration can used. PMID- 24234829 TI - Antifading embedding media in confocal immunoflourescence microscopy. AB - Fading or bleaching of fluorescence intensity during continuous illumination of stained objects is a serious problem in fluorescence microscopy. Fluorescence intensity as well as bleaching characteristics of dyes are dependent primarily upon physical parameters such as molecular constants (absorption rate and quantum efficiency), excitation energy and brightness (causes photon saturation), and environmental parameters (pH, ions, binding to proteins, etc.) that can strongly influence the properties of fluorochrome molecules. We have studied the effect of various antifading reagents on the behavior of the common dyes fluorescein isothiocyanate (FITC) and phycoerythrin (PE) using immunofluorescent-stained living cells in suspension or membrane-permeabilized dried cells as test systems. As expected, fading cannot be completely eliminated but may be reduced to varying degrees. In our hands, the most efficient antifading reagent for FITC isn-propyl gallate (NPG) dissolved in glycerol. No additive was found to retard fading, but complete dehydration of the cell suspension reduces this effect. PMID- 24234830 TI - The relevance of pressure-sensitive paint to aerodynamic research. AB - Aerodynamic tests are designed to give information about the performance of a model when subjected to an airflow. The introduction of pressure sensitive paint provides a new method for obtaining the pressure distribution on the surface of wind-tunnel models. A paint, the luminescence of which is dependent on air pressure, is applied to the surface of the model and the pressure distribution is obtained from the image produced. This paper gives an explanation of this technique, a resume of possible applications and some results from research performed at DRA Bedford. PMID- 24234831 TI - Cationic surfactant/bile salt interaction studied by fluorescence quenching. AB - Fluorescence quenching measurements were performed on aqueous solutions of the cationic surfactant cetyltrimethylammonium halide (CTAX) and two bile salts, sodium cholate (NaC) and sodium deoxycholate (NaDC), to study the state of aggregation in the mixtures. Pyrene was used as a photoluminiscence probe in the study, and dimethylbenzophenone (DMBP) as the quencher. Analysis of time-resolved decay data with and without quencher using a simple kinetic model gave information of the different aggregation characteristics in the above two cases. Mixed micelles of CTAX/NaC were small and spherical at all compositions, while those of CTAX/NaDC tended to grow from spherical micelles to larger rod-like mixed aggregates at equimolar and close-to-equimolar concentrations. In the latter case more complex kinetics ensues and the fluorescence decays were treated using a generatized model for diffusion-controlled quenching along one dimension for infinitely long rod-like micelles. The mutual diffusion coefficient for the probe-quencherpair was determined. PMID- 24234832 TI - Quenching of the excited states of 8-methoxypsoralen by synthetic Eumelanin. AB - The interaction of 8-methoxypsoralen (8-MOP) with synthetic eumelanin was investigated using static and time-resolved fluoresence and pulsed photoacoustic calorimetry. Spectroscopic data indicate the absence of interaction in the ground state, whereas the singlet excited state of 8-MOP is quenched by the pigment; the average fluorescence lifetimes are independent of the melanin concentration, thus indicating a static mechanism. Photoacoustic data show that the quenching process involves an increased intersystem crossing probability, which is almost unaffected by the presence of oxygen, as expected for a molecule essentially acting as a type I photosensitizing agent. PMID- 24234833 TI - Distribution analysis of membrane penetration of proteins by depth-dependent fluorescence quenching. AB - A new approach is presented to evaluate the depth-dependent quenching of the fluorescence of membrane-bound probes and integral proteins. By utilizing at least three quenchers of known and distinctly different depths, the following parameters can be recovered: most probable depth of the probe; dispersion of the depth distribution, which will depend on the size of probe and fluctuations in its position; and quenching efficiency, which is related to the exposure of a particular fluorophore to the lipid phase. The exposure of tryptophan residues in integral proteins can be quantitatively determined with respect to the model compound (tryptophan octyl ester). The proposed method was applied to the investigation of membrane complexes of the bee venom melittin and cytochrome b5. PMID- 24234834 TI - Distance-dependent fluorescence quenching ofN-acetyl-L-tryptophanamide by acrylamide. AB - We examined the time-dependent intensity decays ofN-acetyl-L-tryptophanamide (NATA) when collisionally quenched by acrylamide in propylene glycol over a range of temperatures. The intensity decays of NATA became increasingly heterogeneous in the presence of acrylamide. The NATA intensity decays were not consistent with the Collins-Kimball radiation boundary condition (RBC) model for quenching. The steady-state Stern-Volmer plots show significant upward curvature, and quenching of NATA by acrylamide was observed even in vitrified propylene glycol, where translational diffusion cannot occur during the lifetime of the excited state. These frequencydomain and steady-state data indicate a through-space quenching interaction between NATA and acrylamide, and the results are consistent with a rate constant for quenching that depends exponentially on the fluorophore quencher separation distance. The exponential distance-dependent rate of quenching also explains the upward curvature of the Stern-Volmer plot, and the steady-state data aid in determining the interaction distance between NATA and acrylamide. These results suggest that the distance-dependent quenching rates need to be considered in the interpretation of acrylamide quenching of proteins. PMID- 24234835 TI - Critical Asthma Syndrome in the ICU. AB - Critical asthma syndrome represents the most severe subset of asthma exacerbations, and the critical asthma syndrome is an umbrella term for life threatening asthma, status asthmaticus, and near-fatal asthma. According to the 2007 National Asthma Education and Prevention Program guidelines, a life threatening asthma exacerbation is marked by an inability to speak, a reduced peak expiratory flow rate of <25 % of a patient's personal best, and a failed response to frequent bronchodilator administration and intravenous steroids. Almost all critical asthma syndrome cases require emergency care, and most cases require hospitalization, often in an intensive care unit. Among asthmatics, those with the critical asthma syndrome are difficult to manage and there is little room for error. Patients with the critical asthma syndrome are prone to complications, they utilize immense resources, and they incite anxiety in many care providers. Managing this syndrome is anything but routine, and it requires attention, alacrity, and accuracy. The specific management strategies of adults with the critical asthma syndrome in the hospital with a focus on intensive care are discussed. Topics include the initial assessment for critical illness, initial ventilation management, hemodynamic issues, novel diagnostic tools and interventions, and common pitfalls. We highlight the use of critical care ultrasound, and we provide practical guidelines on how to manage deteriorating patients such as those with pneumothoraces. When standard asthma management fails, we provide experience-driven recommendations coupled with available evidence to guide the care team through advanced treatment. Though we do not discuss medications in detail, we highlight recent advances. PMID- 24234836 TI - Lower anterior cingulate volume in seriously violent men with antisocial personality disorder or schizophrenia and a history of childhood abuse. AB - OBJECTIVE: Antisocial personality disorder (ASPD) and schizophrenia, as well as childhood abuse, are associated with violent behaviour and show marked volumetric reduction in the anterior cingulate (AC), a brain region implicated in regulation of violence through its involvement in decision making, empathy, impulse control, and emotion regulation. The present study examined, for the first time to the authors' knowledge, the grey matter volume of the AC in relation to seriously violent behaviour and childhood psychosocial deprivation (including physical and sexual abuse) in the context of a mental disorder (schizophrenia or ASPD). METHODS: Fifty-seven men [14 with ASPD and a history of serious violence; 13 with schizophrenia and a history of serious violence (VSZ); 15 with schizophrenia without a violence history (SZ); 15 nonviolent healthy participants] underwent whole-brain magnetic resonance imaging and were rated on the presence of physical abuse, sexual abuse, neglect, extreme poverty, foster home placement, criminal parent, severe family conflict, and broken home (collectively 'psychosocial deprivation'). Stereological volumetric ratings of the AC were examined for group differences and their association with childhood psychosocial deprivation. RESULTS: A higher proportion of ASPD and VSZ patients had suffered psychosocial deprivation as children, in particular severe physical abuse, relative to SZ patients and healthy participants. ASPD and VSZ, but not SZ, patients had significantly lower AC volume relative to healthy participants. AC volumes correlated negatively with (total) psychosocial deprivation as well as physical and sexual abuse ratings. Group differences in AC volume became nonsignificant when psychosocial deprivation ratings were covaried for. CONCLUSIONS: Violent mentally disordered individuals with ASPD or schizophrenia suffer from a significant AC volume loss and this deficit, at least in part, is explained by their histories of stressful childhood experiences. Current and future therapies aiming to reduce violence in such populations would benefit by attending to biological (and other) correlates of childhood abuse. PMID- 24234837 TI - Criminal offenses in gamblers anonymous and hospital treated pathological gamblers. AB - The purpose of this study was to compare the nature and prevalence of gambling and non-gambling related offenses in samples of pathological gamblers seeking behavioural treatment from a hospital-based program and those attending Gamblers Anonymous. A semi-structured interview schedule obtaining demographic data and details of the nature, frequency, and consequent legal action of criminal offenses committed was administered to 152 consecutive hospital treated pathological gamblers, and 154 Gamblers Anonymous attendees who volunteered to participate in the study. Of the total sample, 59% admitted a gambling-related offense, and 23% to a conviction. There was no difference in the proportion of hospital treated and Gamblers Anonymous subjects who offended. The most common gambling-related offenses were larceny, embezzlement and misappropriation. Gamblers committed a median of ten offenses over an average ten year period of pathological gambling with a median value of $ A 300(1) per offense. The median value for each non-gambling-related offense was $ A 130. Except for the significantly older mean age of Gamblers Anonymous subjects, hospital treated gamblers did not differ from Gamblers Anonymous attenders on relevant demographic features or parameters of gambling behaviour. Findings were interpreted to suggest a possible causal link between pathological gambling and the commission of non-violent property offenses. PMID- 24234838 TI - Antisocial personality disorder and pathological gambling. AB - The prevalence of antisocial personality disorder and its relationship to criminal offenses in pathological gamblers was investigated. A semi-structured interview schedule containing DSM-III criteria for antisocial personality and the California Psychological Inventory Socialisation subscale was administered to a sample of 306 pathological gamblers. Of the total sample, 35% reported no offense. Forty eight percent admitted to the commission of a gambling related offense, 6% to a non-gambling related offense, and 11% to both types of offense. Fifteen percent of subjects met DSM-III diagnostic criteria for antisocial personality disorder. Though these subjects were at greatest risk for committing criminal offenses, offenses were committed independently of DSM-III antisocial personality disorder in the majority of gamblers. It was concluded that features of antisocial personality emerged in response to repeated attempts to conceal excessive gambling and gambling induced financial difficulties. PMID- 24234839 TI - Factors determining the severity of pathological gambling in males. AB - In extending the implications of our earlier research, we found that a measure of impulsivity developed by Barratt (1965) differentiated recovering, male pathological gamblers (N = 12; mean age = 48.9 years) from male control subjects (N = 15; mean age = 43.3 years). Among the gamblers themselves, however, this measure of impulsivity did not correlate with an index of the social and familial disruption engendered by past gambling. In contrast, a measure of one facet of the gamblers' cognitive style (the TF subscale of the Myers-Briggs Inventory) did correlate with this index of gambling-induced disruption but did not differentiate gamblers from controls. These results, as well as other findings, are discussed in the context of previous research and with regard to the inferential limits imposed by studies of this kind. PMID- 24234840 TI - The gambling lifestyle: I. theory. AB - This paper describes the lifestyle model of gambling behavior in which compulsive gambling behavior is conceptualized as a lifestyle characterized by pseudoresponsibility, self-ascension, hypercompetitiveness, and social rule breaking/bending/ twisting. The underlying premise of this theory is that gambling behavior takes on the appearance of a lifestyle when it is viewed by the individual as a viable means of enhancing self-worth, minimizing personal insecurity, and controlling fear. Three primary areas of theoretical and research interest are covered in this paper: (1) the theoretical underpinnings of lifestyle theory; (2) the individual components (conditions, choice, cognition) of a gambling lifestyle; and (3) the developmental progression of a gambling lifestyle. PMID- 24234841 TI - Male and female betting behaviour: New perspectives. AB - This paper uses an analysis of betting decisions made in offcourse betting offices in the UK to explore differences between the nature of male and female betting behaviour. Specifically gender differences in levels of performance, propensity for risk taking and levels of confidence in betting decisions are considered. The results provide some evidence for greater risk propensity amongst male bettors, lower levels of female bettor confidence in their choices and some degree of performance advantage for women bettors. The results are discussed in relation to previous research; some of the apparent discrepancies are explained in terms of differences in motivational focus and gender differences in definitions of risk-taking and 'successful' performance. In this context areas for future research are highlighted. PMID- 24234842 TI - Communications : A comment on the misperception of streaks. PMID- 24234843 TI - Communications : Comment on review by Dr. Carl Hirsch of behind the eight ball: A Guide for Families Of Gamblers, Journal of Gambling Studies, Volume 9, pp. 201 205. PMID- 24234844 TI - Interaction between VLDL and phosphatidylcholine liposomes generates new gamma LpE-like particles. AB - One of the subfractions of HDL involved in reverse cholesterol transport is gamma LpE. It has been assumed that, like prebeta-LpAI, it can be generated during the interaction between phosphatidylcholine liposomes and lipoproteins and can contribute to more efficient cholesterol efflux after the introduction of liposomes to plasma. However, there has been no evidence concerning what the sources of these particles in plasma might be. Here, we determined whether the interaction of phosphatidylcholine liposomes with VLDL and the subsequent conversions of particles could be a source of new gamma-LpE particles. We found that the interaction between liposomes and VLDL affected its lipid and protein composition. The content of phospholipids increased (~96 %) while the content of free cholesterol and apolipoprotein E decreased in VLDL during the reaction with liposomes (~100 and ~24 %, respectively). New particles which did not contain apolipoprotein B were generated. Heterogeneous HDL-sized populations of particles were generated, containing phospholipids and apolipoprotein E as the sole apolipoprotein, with densities from 1.063 to 1.21 g/ml, either with gamma mobility on agarose gel and Stokes diameters from 8.58 to 22.07 nm or with prebeta-mobility and Stokes diameters from 9.9 to 21.08 nm. The obtained results contribute to the understanding of changes in lipoproteins under the influence of phosphatidylcholine liposomes, showing the formation of new (gamma-LpE)-like and (prebeta-LpE)-like particles, similar in mobility and size to plasma HDL-LpE. These newly generated particles can claim a share of the antiatherogenic effects of liposomes, observed in studies both in vitro and in vivo. PMID- 24234845 TI - Intrathecal miR-96 inhibits Nav1.3 expression and alleviates neuropathic pain in rat following chronic construction injury. AB - MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post transcriptionally by binding to their cognate target mRNAs. Emerging evidence suggests that miRNAs are critical regulators of neuronal functions. The expression pattern of miRNAs in the peripheral nervous system after peripheral nerve injury suggest that miRNAs may have important and yet unknown roles in the mechanisms of pain. Thus, we examined the role of miR-96 in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We found that miR-96 alleviated neuropathic pain. The level of miR-96 was decreased within the ipsilateral dorsal root ganglion (DRG) after peripheral nerve injury but the Nav1.3 level was increased. Specifically, Intrathecal administration of miR-96 suppressed the expression of Nav1.3 induced by CCI. Further examination revealed that miR-96 inhibited the Nav1.3 mRNA expression in the embryonic DRG neurons in vitro. Our findings suggest that miR-96 participate in the regulation of neuropathic pain through inhibiting the expression of Nav1.3 in the DRG of CCI rats. PMID- 24234847 TI - Collision-induced dissociation of alkali metal cationized and permethylated oligosaccharides: Influence of the collision energy and of the collision gas for the assignment of linkage position. AB - Tandem mass spectrometry has been used to study the collision-induced decomposition of [M+Na](+) ions of permethylated oligosaccharides. It is shown that many linkage positions in one compound may be determined by the presence or absence, in a single spectrum, of specific fragment ions that arise from the cleavage of two ring bonds and that the yield of such ions depends strongly on the collision energy and nature of the collision gas. In contrast to the behavior of monolithiated native oligosaccharides, the collision-induced decomposition of the sodiated and permethylated oligosaccharide samples at low energy leads to preferential cleavage of glycosidic linkages. At high collision energies, the fragment ions formed by cleavage of more than one bond are greatly enhanced, especially when helium is replaced by argon as the collision gas. Furthermore, argon is the more efficient collision gas in inducing fragmentation of the precursor ions. As an example of the application of this method, the discrimination between the 1 -> 3 and 1 -> 6-linked mannose residues in the common core of N-glycans is described. PMID- 24234848 TI - Determination of oligonucleotide composition from mass spectrometrically measured molecular weight. AB - Extensive calculations for molecular mass versus subunit composition have been made for oligonucleotides from RNA and DNA to determine the extent to which base compositions might be derived from mass spectrometrically determined molecular weights. In the absence of compositional constraints (e.g., any numbers of A, U, G, C), measurement of molecular weight leads to only modest restrictions in allowable number of base compositions; however, if the compositional value for any one residue is known, such as from selective chemical modification or enzymatic cleavage, the number of allowable base compositions becomes unexpectedly low. For example, hydrolysis of RNA by ribonuclease T1 produces oligonucleotides for which G=1, for which all base compositions can be uniquely specified up to the 14-mer level, solely by measurement of mass to within +/ 0,01%. The effects of methylation, phosphorylation state of nucleotide termini, and knowledge of chain length on the determination of subunit composition are discussed. PMID- 24234849 TI - "Slow" metastable decomposition of oligosaccharide cations produced in an external source fourier transform mass spectrometer. AB - Unimolecular metastable decomposition of cucyclodextrin cations is observed in a fast-atom bombardment Fourier transform mass spectrometry instrument. Cleavage reactions occur at the glycosidic bonds to produce oligomeric fragment ions. The first-order rate constant for the decay of the protonated parent was measured and found to be (4.2 +/- 1.0) * 10(2)s(-1). PMID- 24234850 TI - Metastable ion study of substituted cyclopentadienylmanganese cations in the gas phase. AB - The behavior of some substituted cyclopentadienylmanganese ions has been studied by tandem mass spectrometry. This metastable ion study showed that only C5H5Mn(+) and (C5H4CN)Mn(+) ions retain their nido-cluster structure (1), which is characterized by a simple metal-ligand bond cleavage. Other substituted ions, RXC5H4Mn(+), rearrange to a different extent, depending on the nature of the substituent. The first rearrangement step is R radical migration to the central metal atom, leading to RMnC5H4X(+)-type ions (2). These ions decompose by elimination of X (for X=CO) or with formation of RMnX(+), but further rearrangements can also occur. These are the reverse migration of R from the metal atom to the pi-ligand (for R=H, Ph) and cyclopentadienyl ring expansion (for X=CH2). Collisional activation mass spectra contained an Mn(+) ion peak, which can indicate the existence of stable type 1 structures for most cyclopentadienylmanganese ions. Carboxyl and hydroxymethyl derivatives exist, presumably as ions of type 2. The neutralization-reionization mass spectra of RXC5H4Mn(+) ions are also discussed. PMID- 24234846 TI - Theophylline potentiates lipopolysaccharide-induced NO production in cultured astrocytes. AB - Elucidation of the functions of astrocytes is important for understanding of the pathogenic mechanism of various neurodegenerative diseases. Theophylline is a common drug for bronchial asthma and occasionally develops side-effects, such as acute encephalopathy; although the pathogenic mechanism of the side-effects is unknown. The lipopolysaccharide (LPS)-induced nitricoxide (NO) production is generally used for an index of the activation of astrocyte in vitro. In this study, in order to elucidate the effect of theophylline on the astrocytic functions, we examined the LPS-induced NO production and the expression of iNOS in cultured rat cortex astrocytes.Theophylline alone could not induce the NO production; however, NO production induced by LPS was enhanced by theophylline in a dose-dependent manner; and by isobutylmethylxanthine, a phosphodiesterase inhibitor. The theophylline enhancement of LPS-induced NO production was further increased by dibutyryl cyclic AMP, a membrane-permeable cAMP analog; and by forskolin, an adenylate cyclase activator. When the cells were preincubated with Rp-8-Br-cAMP, an inhibitor of protein kinase A, the theophylline enhancement of LPS-induced NO production was decreased. The extent of iNOS protein expression induced by LPS was also enhanced by theophylline.It is likely that phosphodiesterase inhibition is a major action mechanism for the theophylline enhancement of LPS-induced NO production in astrocytes. Theophylline-induced acute encephalopathy might be due to the hyper-activation of astrocytes via cAMP signaling to produce excess amount of NO. PMID- 24234851 TI - Low-energy tandem mass spectrometry of the molecular ion derived from fatty acid methyl esters: A novel method for analysis of branched-chain fatty acids. AB - Low-energy collision-induced dissociation (CID) of the molecular ions of fatty acid methyl esters obtained by electron ionization (70 eV) decompose in the tandem quadrupole mass spectrometer to yield a regular homologous series of carbomethoxy ions. Even at energies up to 200 eV (E lab), primarily carbomethoxy ions are present, with the most abundant found at m/z 101 at hi her energies. The lack of any other CID ions, including m/z 74 (McLafferty rearrangement) or m/z 87, suggest a rearranged molecular ion structure on leaving the first quadrupole mass analyzer. Analyses of various stable isotope variants support the hypothesis of alkyl radical migration to the carboxy carbonyl oxygen atom, with subsequent radical site directed cleavage either with or without a cyclization event. Decomposition of the molecular ions (70 eV) of several methyl branched fatty acid methyl esters, including phytanic acid, iso-methyl and anteiso-methyl branched acids, and tuberculostearic acid, reveals enhanced radical site cleavage at the alkyl branching positions. This method can be used to readily determine methyl (or alkyl) branching positions in a saturated fatty acid methyl ester. PMID- 24234852 TI - An investigation of site-selective gas-phase reactions of amino alcohols with dimethyl ether ions. AB - The reactions of dimethyl ether ions with neutral amino alcohols were examined in both a quadrupole ion trap mass spectrometer and a triple quadrupole mass spectrometer. These ion-molecule reactions produced two types of ions: the protonated species [M+l](+) and a more complex product at [M+13](+). The abundance of the [M+13](+) ions relative to that of the [M+1](+) ions decreases with increasing formal interfunctional distance. Multistage collision-activated dissociation techniques were used to characterize the [M+13](+) product ions, their reactivities, and the mechanisms for their formation and dissociation. In addition, molecular semiempirical calculation methods were used to probe the thermochemistry of these reactions. Reaction at the amino alcohol nitrogen site is favored, and the resulting [M+13](+) addition products may cyclize for additional stabilization. Comparisons were made among the behavior of related compounds, such as alcohols, diols, amines, and diamines. The alcohols reacted only to form the protonated species, but the diols, amines, and diamines all formed significant amounts of [M+13](+) ions or related dissociation products. PMID- 24234853 TI - Gas-phase complexation of polyethers with halide ions. AB - Gas-phase complexes of halide anions with a variety of crown ethers and acyclic analogs are formed by ion-molecule reactions in the chemical ionization source of a triple-quadrupole mass spectrometer. The ether complexes of iodide, bromide, and chloride dissociate on collisional activation by cleavage of the halide-ether electrostatic hydrogen bonds, resulting in the formation of bare halide anions. By contrast, the fluoride complexes dissociate by loss of HF, which may occur in conjunction or sequentially with losses of ethylene oxide units. This dissociation behavior is similar to that observed for collisionally activated dissociation of [M - H](-) ions of the crown ethers and suggests that the fluoride ion is capable of promoting an intramolecular proton abstraction within the [M+F](-) complex. This type of dissociation chemistry is only observed for the fluoride ion complexes, and the fluoride ion is the most basic of all the halides. The kinetic method was used to establish orders of relative halide binding strengths, and the trends for the chloride and bromide affinities were 12 crown-4 < triethylene glycol dimethyl ether < 15-crown-5 < tetraethylene glycol dimethyl ether < 18-crown-6 < 21-crown-7 < tetraethylene glycol < pentaethylene glycol < 1,4,7,10,13-pentathiacyclopentadecane. PMID- 24234854 TI - A study on the solution and gas-phase chemistry of Mn(III) and Fe(III) tetraarylporphyrin complexes by fast-atom bombardment mass spectrometry : 1: Generation of molecular signals. AB - Fast-atom bombardment mass spectrometry has been used to investigate the chemical behavior of Fe(III) and Mn(III) tetraarylporphyrins (TAP) in both the condensed and gas phases and to clarify the mechanisms responsible for the production of positive and negative ions. The differences in the behavior of Fe(III) and Mn(III) complexes in the positive ion mode could be correlated with those in their electronic structures and knowledge of the mechanism for the generation of negatively charged species was applied to characterize the counterion coordinated to the Mn(III)-TAP. Thus, the unprecedented, complete characterization of even complex Mn(III)-TAP was made possible. PMID- 24234855 TI - A study on the solution and gas-phase chemistry of Mn(III) and Fe(III) tetraarylporphyrin complexes by fast-atom bombardment mass spectrometry : 2: Synthesis and characterization of molecular complexes federico maria rubino. AB - The chemical behavior of Fe(III) and M(III) tetraarylporphorin (TAP) complexes with N-alkylimidazoles and other suitable ligands was studied by direct reaction in the fast-atom bombardment matrix and in the gas phase. The coordination reaction occurs at the metal center and yields molecular adducts of porphyry/ligand (PL) and PL, stoichiometry. Coordinative competition between free and covalently linked ligands can be used to probe the conformation of "tailed" Mn(III)-TAP. PMID- 24234856 TI - Injection of reagent ions into the selvedge region in fast-atom bombardment mass spectrometry. AB - A divided probe that incorporates a potassium aluminosilicate glass target and an analyte/glycerol matrix target, spatially separated, was used to inject potassium ions (K(+)) into the high-pressure "selvedge" region formed above the analyte/glycerol matrix target during fast-atom bombardment (FAB); [M+K](+) adduct ions that represent the types of gas-phase neutral molecules present in the selvedge region are observed. Computer modeling assisted in designing the divided target and an additional ion optical element for the FAB ion source to optimize interactions between K(+) ions and the desorbed neutral molecules. The capability of injecting K(+) ions into the FAB experiment has utility in both mechanistic studies and analyses. Experimental results here are consistent with a model for the desorption/ionization processes in FAB in which some types of neutral analyte molecules are desorbed intact and are subsequently protonated by glycerol chemical ionization. Unstable protonated molecules undergo unimolecular decomposition to yield observed fragment ions. The use of K(+) cationization of analytes for molecular weight confirmation is demonstrated, as well as its utility in FAB experiments in which mixtures are encountered. PMID- 24234857 TI - Why are electron capture negative ion mass spectra not reproducible? An ion source problem. AB - Differences in the electron capture negative ion mass spectra of environmentally related organic compounds acquired on a VG 30-250 triple quadruple mass spectrometer and on an HP 5985B gas chromatography/mass spectrometry system were investigated with respect to the ion formation process. Neither ion source temperature nor pressure was responsible for the differences. The populations of thermal electrons in both ion sources were experimentally determined and found to be similar, suggesting that electron capturing reactions should proceed with comparable efficiencies in both ion sources. The ion extraction efficiencies of the two instruments were examined by monitoring the transmission profiles of low- and high-mass ions as a function of lens potentials. Results indicated that the HP 5985B extraction lens significantly suppressed low-mass ions. Further, theoretical evaluation of ion trajectories using SIMION suggested that on the HP 5985B, low-mass ions entered the mass analyzer as a defocused beam, but high-mass ions entered the analyzer as a well-collimated beam. On the VG 30-250, low- and high-mass ions were transmitted to the analyzer with equal efficiency by the ion extraction system. PMID- 24234858 TI - Relative ion yields measured with a high-resolution glow discharge mass spectrometer operated with an argon/hydrogen mixture. AB - Quantitative elemental analysis by glow discharge mass spectrometry (GDMS) requires a calibration factor for each element. The calibration factors used in the present work are called relative ion yields (RIYs). The RIYs of each of 19 elements within samples of four National Institute of Standards and Technology steel reference materials (nos. 661-664) were measured using pure argon and an argon mixture containing 1.0% hydrogen by volume. The RIYs measured using pure argon correlated within a factor of approximately 2-3 to the RIYs calculated by a theoretical model. The RlYs measured for these 19 elements using the argon mixture containing 1.0% hydrogen correlated within a factor of approximately 1.3 to the calculated RIYs. These results may have significant analytical potential with respect to GDMS and may have application to other plasma techniques. PMID- 24234860 TI - A methodological review of models used to estimate the cost effectiveness of antiretroviral regimens for the treatment of HIV infection. AB - The aim of this article was to perform a detailed methodological review of models used to estimate the cost effectiveness of drug treatment regimens for HIV infection in Europe and North America and assess the relationship between the different modeling approaches or key structural assumptions and the results. Electronic searches in three databases (MEDLINE, EMBASE, and the Cochrane Library) identified the cost-effectiveness models. Modeling approaches and structural assumptions were abstracted for all models. For three case studies of multiple analyses that compared the cost effectiveness of two drug regimens using the same clinical data inputs, differences in results were compared with differences in modeling approaches and structural assumptions. Forty-one model publications were reviewed. Recent models included Monte Carlo simulations, Markov models, or discrete-event simulation models, all including multiple lines of therapy and capturing the long-expected duration of efficacy of highly active antiretroviral therapy. In the three case studies, assumptions about the duration of efficacy after the trial time period, whether differences between the two regimens persist after the trial time period, the sequence of regimens after initial regimen failure, and the cost and utility assigned to adverse events, but not the modeling approach, were the most important factors in explaining differences in the results. As the models and treatment pathways get more complex, models should be validated using clinical trial data and local observational databases. The results of sensitivity analyses testing the impact of the structural assumptions that might change the results as identified in this review should also be presented in modeling papers. PMID- 24234862 TI - Negative ion electrospray mass spectrometry of nucleotides: ionization from water solution with SF6 discharge suppression. AB - The total current and selected ion currents from the electrospray ionization (ES1) of 10(-5) M solutions of cocaine hydrochloride and deoxycytidine monophosphate (dCMP) monosodium salt in methanol and water solvents were compared in positive and negative ion modes, respectively, without and with SF6, gas as a discharge suppressant. The ESI onset voltages (Von), were the same for the positive and negative ion modes. The Von, for methanol was much lower than that for water and in agreement with the equation of D. P. H. Smith, who attributes the difference to the higher surface tension of water. The onset of electric discharge (Vdis) without SF6, occurred at lower capillary voltages for the negative relative to the positive ion mode for methanol; but Vdis is much higher than Von for methanol, and discharges do not interfere with ESI operation. For water, Von ~ Vdis in the absence of SF6, in the negative ion mode, and ESI operation is impossible without SF6, discharge suppression. The discharge problem in the positive ion mode is less severe, but SF6, is still very useful. A dynamic range of 10 (-7)-10(-5) M was obtained by selected ion monitoring of [dCMP - H]( ) at 4.5 and 20 MUL/min. flows. Subpicomole detection limits for the nucleotide salt were obtained under these conditions. PMID- 24234861 TI - In-vitro and in-vivo imaging of prostate tumor using NaYF4: Yb, Er up-converting nanoparticles. AB - The aim of this study was to investigate the feasibility of prostate tumor bioimaging both in vitro and in vivo using an upconversion fluorophore, NaYF4: Yb, Er nanoparticles. Luminescent signals of human prostate cancer cells (CWR22R and LNCaP) labeled with NaYF4: Yb, Er nanoparticles were detected by laser scanning confocal microscope, while Cy3 or FITC was used as control probe. Mouse human prostate cancer model was developed by subcutaneously injecting the CWR22R cells into BALB/c nude mice to investigate the in-vivo imaging properties of NaYF4:Yb, Er nanoparticles. Both CWR22R and LNCaP cells could phagocytose NaYF4:Yb, Er nanoparticles in vitro, and the cellular uptake of CWR22R cells was much higher than that of LNCaP cells (95.42 +/- 3.47 % vs. 51.63 +/- 6.43 %), which made us choose the former for the further study. CWR22R cells pre-labeled with NaYF4:Yb, Er nanoparticles showed no obvious decrease of fluorescence intensity (P > 0.05) after light exposure, while the fluorescence intensity of Cy3 or FITC labeled cells decreased rapidly with prolonged bleaching (P < 0.05). Furthermore, the in-vivo results showed that the prostate cancer cells pre labeled with or without NaYF4:Yb, Er nanoparticles formed tumors 4 weeks after injection, and the tumor length-diameter of the nanoparticle group and the control group was (10.3 +/- 2.0) mm and (9.8 +/- 2.5) mm, respectively. Significant upconversion fluorescence signals were observed in the tumors of the nanoparticle group when being excited at 980 nm by a NIR laser. In summary, the results suggest that as an intensive fluorescence imaging label agent, NaYF4:Yb, Er nanoparticles possess unique features and can be used for imaging prostate tumor cells both in vitro and in vivo by phagocytosis. PMID- 24234863 TI - Methyl guanine isomer distinction by hydrogen / deuterium exchange using a fourier transform mass spectrometer. AB - Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA Differentiation of the seven isomers of methyl guanine has been accomplished by monitoring gas-phase hydrogen/deuterium (H/D) exchange reactions of the protonated molecular ions with deuterium oxide (D2O) in a Fourier transform mass spectrometer. In each case a distinctive reaction rate for the first H/D exchange was observed, and exchanges of up to three deuterium atoms occurred with characteristic ion abundances that could be used to differentiate the isomers. O(6)-Methyl guanine, for example, showed only one slow H/D exchange with D2O, whereas l-methyl guanine exchanged two hydrogen atoms at a significantly faster rate. On comparison of the possible resonance structures of each protonated isomer with the experimental information about the number and rate of H/D exchanges observed, a reaction mechanism involving a concerted proton abstraction-deuterium cation donation was proposed. PMID- 24234864 TI - Redox processes of ruthenium (II) polypyridine complexes induced by fast-atom bombardment mass spectrometry. AB - Fast-atom bombardment (FAB) mass spectrometry in the negative ionization mode enables the sputtering into the gas phase of the ruthenium complexes [Ru(2,2' bipyridine[bpy])2(2,5-bis) (pyrydil)pyrazine[dpp])](PF6)2; [Ru(bpy)2,(2,3dpp)](PF6)2;[Ru(bpy)2,(2,3-dpp-Me)]( PF6)3; and [Ru(bpy)2(omega-2,3 dpp)]2 RuCl2(PF6)4 as intact radical anions. These data, combined with those avaiiable from the positive FAB spectra allow a full characterization of the analytes. PMID- 24234865 TI - Characterization of beam-induced reactions occurring in liquid secondary ion mass spectrometry/fast-atom bombardment by tandem mass spectrometry. AB - Department of General and Physical Chemistry, University of Liege, Liege, Belgium A specific beam-induced secondary reaction involving the condensation of hydroxylic matrices with some organic groups (aldehydes, ketones, etc.) accompanied by the loss of a water molecule was investigated by liquid secondary ion mass spectrometry/fast-atom bombardment (LSIMS/FAB). A mechanistic scheme and a structure of the induced product are proposed. The features of this secondary reaction were studied and the influence of the types of solutes, acidic additives, and matrices analyzed. Rather than a drawback, LSIMS/FAB mass spectrometry can take advantage of this matrix effect to infer analytical information through tandem mass spectrometry experiments. Specific neutral loss scans can be conducted to highlight beam-induced reactive molecules, even when the detection of these species is prevented in normal scan spectra by other surface-active components. PMID- 24234866 TI - Selective chemical ionization of nitrogen and sulfur heterocycles in petroleum fractions by ion trap mass spectrometry. AB - A procedure is reported for the selective ammonia chemical ionization of some nitrogen and sulfur heterocycles in petroleum fractions using ion trap mass spectrometry (ITMS). The ion trap scan routine is designed to optimize the population of ammonium reagent ions and eject from the trap (by radio frequency/direct current isolation) electron ionization products formed during reagent ion formation prior to ionization of the sample. The ITMS procedure is compared with standard ion trap detector and conventional quadrupole ammonia chemical ionization for the determination of nitrogen and sulfur heterocycles in gas oil and kerosine samples. Greatly enhanced selectivity is shown for the ITMS procedure by suppression of competing charge-exchange processes. PMID- 24234867 TI - Trimethylsilyl group migration in the mass spectra of trimethylsilyl ethers of cholesterol oxidation products. product ion characterization by linked-scan tandem mass spectrometry. AB - Loss of the A ring in the electron-impact mass spectra of the trimethylsilyl (TMS) derivatives of several cholesterol oxidation products is accompanied by intramolecular migration of the 3-O-TMS group to the charge-retaining portion of the molecule. Linked-scan techniques (B/E and B(2)/E) were used to establish the fragmentation processes leading to the formation of the rearrangement ion. The TMS group appears to migrate to heteroatomic sites in the 5-; 6-, or 7-positions of the B ring. This structural assignment is supported by isotopic labeling studies and collision-induced dissociation of the resulting product ion. PMID- 24234868 TI - Gas chromatographic-mass spectrometric method for the assessment of oxidative damage to double-stranded dna by quantification of thymine glycol residues. AB - A technique for the measurement of thymine glycol at parts per million concentrations in double-stranded polymeric DNA is described. The procedure utilizes base to ring-open DNA-bound thymine glycol in the presence of monomeric [(2)H4]thymine glycol as an internal standard, followed by reduction, solvolytic cleavage, and quantification of the characteristic methyl-2-methylglycerate released from polymeric DNA. Methyl-2-methyl-glycerate is derivatized to form the di-tert-butyldimethylsilyl [(TBDMS)2] ether to enhance its gas chromatographic properties and electron ionization detection. This assay was tested by measuring thymine gIyco1 levels in native, undamaged DNA (not purposefully oxidized). The measured quantities of thymine glycol are proportional to the amount of DNA analyzed. Components of DNA not containing oxidizable thymine do not contribute to the measured signal from methyl-2-methylglycerate-(TBDMS)2. These results indicate that there is approximately one thymine glycol per lo6 bases in undamaged DNA and that this value increases with storage of DNA in refrigerated aqueous solutions. PMID- 24234869 TI - Ion-dipole complex formation from deprotonated phenol fatty acid esters evidenced by using gas-phase labeling combined with tandem mass spectrometry. AB - The behavior of para-hydroxy-benzyl and hydroxy-phenylethyl fatty acid esters and methoxy derivatives toward the NH3/NH2 (-) system was investigated. Under these negative ion chemical ionization (NICI) conditions, proton abstraction takes place mainly at the more acidic site (i.e., phenol); however, this reaction is not entirely regioselective. Using NICI-ND3 conditions, both isomeric phenoxide and enolate molecular species are produced in competition from these phenol esters. Their respective low-energy collision-activated dissociation spectra are studied, and they strongly differ, showing that these molecular species are not convertible to a common structure. Analysis of specific fragmentations of the OD enolate parent species labeled by ND3 in the gas phase, indicates that by charge promoted cleavage, isomerization into an ion-dipole intermediate takes place prior to dissociation. This complex, containing a ketene moiety, isomerizes into different isomeric forms via two consecutive proton transfers: the first, which is very exothermic, is irreversible in contrast to the second, less exothermic reaction, which occurs via a reversible process. It is evidenced by the loss of labeling at phenol or enolizable sites in the fragment ions. Such a stepwise process does not take place from the phenoxide parent ion, which preferentially yields a very stable carboxylate ion. A thermochemical approach, using estimated acidity values, yields a rationalization of the observed reactivities of the various substrates studied. PMID- 24234870 TI - Selective ion-molecule reactions of lactams with dimethyl ether ions. AB - The ion-molecule reactions of dimethyl ether ions CH3OCH3 (+) and (CH3OCH3)H(+), and four- to seven-membered ring lactams with methyl substituents in various positions were characterized by using a quadrupole ion trap mass spectrometer and a triple-quadrupole mass spectrometer. In both instruments, the lactams were protonated by dimethyl ether ions and formed various combinations of [M + 13] (+), [M + 15] (+), and [M + 45] (+) adduct ions, as well as unusual [M + 3] (+) and [M + 16] (+) adduct ions. An additional [M + 47] (+) adduct ion was formed in the conventional chemical ionization source of the triple-quadrupole mass spectrometer. The product ions were isolated and collisionally activated in the quadrupole ion trap to understand formation pathways, structures, and characteristic dissociation pathways. Sequential activation experiments were performed to elucidate fragment ion structures and stepwise dissociation sequences. Protonated lactams dissociate by loss of water, ammonia, or methylamine; ammonia and carbon monoxide; and water and ammonia or methylamine. The [M + 16] (+) products, which are identified as protonated lactone structures, are only formed by those lactams that do not have an N-methyl substituent. The ion-molecule reactions of dimethyl ether ions with lactams were compared with those of analogous amides and lactones. PMID- 24234871 TI - To the editor. PMID- 24234876 TI - Sustainable development : Symbiosis of environmental science, economics and social sciences. PMID- 24234873 TI - Translational approaches to anxiety: focus on genetics, fear extinction and brain imaging. AB - Anxiety disorders are highly prevalent and debilitating psychiatric disorders. Owing to the complex aetiology of anxiety disorders, translational studies involving multiple approaches, including human and animal genetics, molecular, endocrinological and imaging studies, are needed to get a converging picture of function or dysfunction of anxiety-related circuits. An advantage of anxiety disorders is that the neural circuitry of fear is comparatively well understood, with striking analogies between animal and human models, and this article aims to provide a brief overview of current translational approaches to anxiety. Experimental models that involve similar tasks in animals and humans, such as fear conditioning and extinction, seem particularly promising and can be readily integrated with imaging, behavioural and physiological readouts. The cross validation between animal and human genetics models is essential to examine the relevance of candidate genes, as well as their neural pathways, for anxiety disorders; a recent example of such cross-validation work is provided by preclinical and clinical work on TMEM132D, which has been identified as a candidate gene for panic disorder. Further integration of epigenetic data and gene * environment interaction are promising approaches, as highlighted by FKPB5 and PACAP, early life trauma and stress-related anxiety disorders. Finally, connecting genetic and epigenetic data with functionally relevant imaging readouts will allow a comparison of overlap and differences across species in mechanistic pathways from genes to brain functioning and behaviour. PMID- 24234877 TI - Reciprocal effects of platinum and lead on the water household of poplar cuttings. AB - In order to study the accumulation rates and effects of platinum as influenced by lead, experiments were performed with poplar cuttings in a growth chamber. The heavy metals were added at a final concentration of 34.8 ppb each to nutrient solutions as PtCl4 and Pb(NO3)2. The variants were 1) control; 2) permanent Pt treatment for 6 weeks; 3) pretreatment with Pt plus subsequent treatment with Pb (three weeks each), and 4) heavy metal application in inverse order to variant 3.The experiments revealed that platinum accumulates in the roots of poplar cuttings to a higher degree than lead. It is translocated from the roots to other plant parts to an extremely low degree. Lead is displaced from the roots by subsequent Pt treatment. Insoluble platinum was found to be associated especially on the cell walls of the rhizodermis and exodermis of the root tips.Accumulation of platinum in the roots leads to a gradual depletion of the plants' water supply. The disturbance of the water household causes a reduction of the transpirational surface, lowered transpiration rates and enhanced root growth. All these alterations are induced as a means of coping water stress.From the results of this experiment, the conclusion can be drawn that, under the chosen experimental conditions, platinum manifests a higher toxicity than lead in plant roots because of its higher accumulation rates. PMID- 24234875 TI - Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. AB - BACKGROUND: Heavy menstrual bleeding is one of the most common reasons for referral of premenopausal women to a gynaecologist. Although medical therapy is generally first line, many women eventually will require further treatment. Endometrial ablation by hysteroscopic and more recent "second-generation" devices such as balloon, radiofrequency or microwave ablation offers a day-case surgical alternative to hysterectomy. Complete endometrial destruction is one of the main determinants of treatment success. Surgery is most effective if undertaken when endometrial thickness is less than four millimeters. One option is to perform the surgery in the immediate postmenstrual phase, which is not always practical. The other option is to use hormonal agents that induce endometrial thinning pre operatively. The most commonly evaluated agents are goserelin (a gonadotrophin releasing hormone analogue, or GnRHa) and danazol. Other GnRH analogues and progestogens have also been studied, although fewer data are available. It has been suggested that these agents will reduce operating time, improve the intrauterine operating environment and reduce absorption of fluid used for intraoperative uterine cavity distension. They may also improve long-term outcomes, including menstrual loss and dysmenorrhoea. OBJECTIVES: To investigate the effectiveness and safety of pre-operative endometrial thinning agents (GnRH agonists, danazol, estrogen-progestins and progestogens) versus another agent or placebo when given before endometrial destruction in premenopausal women with heavy menstrual bleeding. SEARCH METHODS: The following electronic databases were searched to April 2013 for published and unpublished randomised controlled trials that met the inclusion criteria: the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO.Other electronic sources of trials included trial registers for ongoing and registered trials; citation indexes; conference abstracts in the Web of Knowledge; the LILACS database for trials from the Portuguese- and Spanish-speaking world; PubMed; and the OpenSIGLE database and Google for grey literature.All searches were performed in consultation with the MDSG Trials Search Co-ordinator. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included if they compared the effects of these agents with one other, or with placebo or no treatment, on relevant intraoperative and postoperative treatment outcomes. Selection of trials was carried out independently by two review authors. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for risk of bias and extracted data on surgical outcomes, effectiveness outcomes, proportion of women requiring further surgical therapy during follow-up, endometrial outcome measures, acceptability of use outcomes and quality of life. Data were analysed on an intention-to-treat basis. Dichotomous data were combined for meta-analysis with RevMan software using the Mantel-Haenszel method to estimate pooled risk ratios (RRs). Continuous data were combined for meta analysis with RevMan software using an inverse variance method to estimate the pooled mean difference (MD) with 95% confidence interval (CI). The overall quality of evidence for the main findings was assessed with the use of GRADE working group methods. MAIN RESULTS: Twenty studies with 1969 women were included in this review. These studies compared GnRHa, danazol and progestogens versus placebo or no treatment; GnRHa versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison.When compared with no treatment, GnRHa used before hysteroscopic resection were associated with a higher rate of postoperative amenorrhoea at 12 months (RR 1.6, 95% CI 1.2 to 2.0, 7 RCTs, 605 women, moderate heterogeneity; I(2) = 40%) and at 24 months (RR 1.62, 95% CI 1.04 to 2.52, 2 RCTs, 357 women, no heterogeneity; I(2) = 0%), a slightly shorter duration of surgery (-3.5 minutes, 95% CI -4.7 to -2.3, 5 RCTs, 156 women, substantial heterogeneity; I(2) = 72%) and greater ease of surgery (RR 0.32, 95% CI 0.22 to 0.46, 2 RCTs, 415 women, low heterogeneity; I(2) = 4%). Postoperative dysmenorrhoea was reduced (RR 0.59, 95% CI 0.40 to 0.87, 2 RCTs, 133 women, no heterogeneity; I(2) = 0%). The use of GnRHa had no effect on intraoperative complication rates (RR 1.47, 95% CI 0.35 to 6.06, 5 RCTs, 592 women, no heterogeneity; I(2) = 0%), and participant satisfaction with this surgery was high irrespective of the use of pre-operative endometrial thinning agents (RR 0.99, 95% CI 0.93 to 1.05, 6 RCTs, 599 women, low heterogeneity; I(2) = 11%). GnRHa produced more consistent endometrial atrophy than was produced by danazol (RR 1.84, 95% CI 1.23 to 2.75, 2 RCTs, 142 women, no heterogeneity; I(2) = 0%). For other intraoperative and postoperative outcomes, any differences were minimal, and no benefits of GnRHa pretreatment were noted in studies in which women underwent second-generation ablation techniques. Both GnRHa and danazol produced side effects in a significant proportion of women, although few studies reported these in detail. Few randomised data were available to allow assessment of the effectiveness of progestogens as endometrial thinning agents. When reported, the long-term effects of endometrial thinning agents on benefits such as postoperative amenorrhoea were reduced with time.The main study weaknesses were that most participants received no follow-up beyond 24 months and that the studies used a small sample size. Heterogeneity for outcomes reported ranged from none to substantial. More than half the trials had no blinding of participants or outcome assessment. Most of the trials were determined to have uncertain selection and reporting bias, as they did not report allocation concealment and evidence of selective reporting was noted. The quality of reporting of adverse events was generally poor, but, when described in the studies, they included menopausal symptoms such as hot flushes, vaginal dryness, hirsutism, decreased libido and voice changes, as well as other side effects such as headache and weight gain. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that endometrial thinning with GnRHa and danazol before hysteroscopic surgery improves operating conditions and short-term postoperative outcomes. GnRHa produced slightly more consistent endometrial thinning than was produced by danazol, although both achieved satisfactory results. The effect of these agents on longer-term postoperative outcomes was reduced with time. No benefits of GnRHa pretreatment were apparent with second-generation ablation techniques. Also, side effects were more common when these agents were used. PMID- 24234878 TI - Statistical analysis of heavy metal data from municipal waste incineration residues. AB - Heavy Metal data from a measurement program at a municipal incinerator in Vienna, Austria are analysed. The experimental design had a nested structure, and analysis of variance is used to break down the total variability into several components; (1) variability between mean hourly concentrations, (2) variability between mean sample concentrations within intervals of an hour and (3) variability due to "measurement" errors. Results of a pre-experiment show, that if grab samples are taken, within hour variation is dominant. The results of analysis of variance were used to calculate an optimal number of samples, which ensure a predetermined accuracy for the mean concentrations. In two main measuring periods with different incinerated waste types, slag and fly ash (ESP dust and boiler ash) data are produced and analysed. For both slag and fly ash, significant differences in measures of location and dispersion between the data sets of the main experiment are found. This proves, that differences in the chemical set up of waste can be detected via incineration residues. PMID- 24234874 TI - Medical consequences of marijuana use: a review of current literature. AB - With the advent of legalization of marijuana for medicinal and recreational purposes, and the increase use of marijuana, healthcare providers will be increasingly confronted with marijuana users as patients in clinical environments. While there is vast literature regarding the societal and mental health harms associated with marijuana use, there is a paucity of reviews of the potential consequences of marijuana use on physical health or medical conditions. We examine the recent literature on the physical harms associated with illicit and legal marijuana administration. We surveyed the peer-reviewed medical literature from 1998 to 2013 of studies assessing the association of marijuana use and physical diseases. We conclude that healthcare providers should be cognizant that the existing literature suggests that marijuana use can cause physical harm. However, evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions. PMID- 24234879 TI - Erratum. PMID- 24234880 TI - Free phosphine from the anaerobic biosphere. AB - The possible liberation of highly toxic and mutagenic phosphine from putrefying media raises the question of its significance as a problem of hygiene. Free phosphine was established by gas chromatography as a universal trace component in gas emitted from the anaerobic biosphere. Sources of phosphine include landfills, compost processing, sewage sludge, animal slurry and river sediments. We detected maximum concentrations in the order of 20 ppb(v/v). PMID- 24234881 TI - Catalytic oxidation for air pollution control. AB - Bench-scale experiments have been conducted to evaluate a series of titania supported Pt-Pd (as oxides) catalysts in the presence and absence of MoO3 and Fe2O3 additives for their effectiveness in the complete catalytic oxidation of volatile organic compounds (VOCs) in air likely to be found in waste gases. Under oxidizing conditions, all of the catalysts promoted the complete oxidation of VOCs to CO2 and H2O. 99 % Conversion was achieved with a C2H4-C2H6 gas mixture in air at temperatures between about 160-450 degrees C and at a space velocity of 20,000 h(-1). Oxidation activity for the titania supported catalysts were found to decrease in the order Pt-Pd-Mo-Fe > Pt-Pd-Mo > Pt-Pd-Fe > Pt-Pd. However, the addition of MoO3 and Fe2O3 increase the catalyst activity and reduce the reaction temperature for the complete destruction. Ageing was also performed in order to study the stability of the most active catalyst. Pt-Pd-Mo-Fe (as oxides) on titania catalyst is effective in oxidizing a wide range of volatile organic compounds at relatively low temperatures (220-405 degrees C) and and at a space velocity of 40,000 h(-1) and is resistant to poisoning by halogenated and amine volatile organic compounds. PMID- 24234882 TI - Air quality guidelines for Europe. PMID- 24234883 TI - Site selection for new hazardous waste management facilities. PMID- 24234884 TI - Polycyclic aromatic hydrocarbons (PAH) in different forest humus types. AB - The behavior of 20 PAH in the organic layers of a L mull, an Of mull and a mor was assessed by a combined approach of a soil profile study, and the analysis of particle-size separates. Increasing PAH concentrations with depth in the mor profile (L, 866 MUg kg(-3); Of, 2902 MUg kg(-1); Oh, 10489 ug kg(-1)) were assigned to selective enrichment during organic matter decomposition. PAH were further highly enriched within the finer separates. For the L horizons, significant positive correlations were established between the enrichment of individual PAH (as observed from the decomposition gradient between the >2-mm fraction and the < 0.05-mm fraction), and the KOW for each compound. The slope of the regression line, m, described the degree of differentiation between low- and high-molecular PAH during litter decomposition. Since m was greatest in the most biologically active humus type (L mull, 0.33) and smallest in the most inactive (mor, 0.20), microbial breakdown was assumed as the dominating process for this differentiation. The results also indicated that decomposition processes had already taken place in the L horizons, leading to morphological and chemical changes of organic matter, and to an enrichment of high molecular PAH. PMID- 24234886 TI - Bioassays for soils. PMID- 24234885 TI - Clearance of atrazine in soil describing xenobiotic behavior. AB - The primary aim of this study was to evaluate the "clearance concept" as a tool for describing the behavior of xenobiotic movement into and through soils. As an example, degradation of 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (atrazine) with the formation of metabolites 2-chloro-6-isopropylamino-s-triazine (desethylatrazine) and 2-chloro-4-ethylamino-s-triazine (desisopropylatrazine) was investigated. Atrazine was sprayed post-emergently in doses of 0.125 or 0.5 g active ingredient/m(2) each on four test plots. Soil type was a sandy-loam, on which corn (Zea mays L.) was cultivated. Soil samples were taken as cores of 0.2 m depth 0, 1, 2, 4, 8, 12, 16 and 20 weeks after application of atrazine, and analyzed by HPLC. Soil concentrations of atrazine were highly correlated (r=0.993, p< 0.001) between the two applications of 0.125 g/m(2) and 0.5 g/m(2). Up to 50% of the atrazine was measured as metabolites during the whole vegetation period. Clearance of atrazine from soil was calculated as the total load of atrazine divided by the area under the soil atrazine concentration time curve. Soil atrazine clearance was calculated as 5.13 +/- SD 1.10 and 5.17 +/- SD 1.02 liter of soil per day for doses of 0.125 g/m(2) and 0.5 g/m(2), respectively (from a "soil unit" of 1 * 1 * 0.2 meter). The clearance concept might be a tool for risk assessment of xenobiotics. PMID- 24234887 TI - Spatial variability in compartmental fate modelling : Linking fugacity models and GIS. AB - A new approach is presented which is designed to address the spatial heterogeneity of the environment in compartmental mass balance models of chemical fate in the environment. It rests on the assumption of chemical equilibration within one phase despite prevailing environmental heterogeneity. Composite D- and Z-values are derived from sub-unit specific environmental parameters and are used to solve mass balance equations which can be adopted essentially unchanged from existing compartmental fugacity models. With the resulting common fugacity value for each compartment, sub-unit specific concentrations and process rates can be calculated. The approach is illustrated using the QWASI lake model to calculate the fate of hexachlorobenzene in a hypothetical lake sub-divided in four distinct sub-units. The approach allows the subdivision of each compartment in a large number of sub-units with distinct environmental characteristics without substantially increasing model complexity. This is a necessary condition for linking fugacity models to geographical information systems. PMID- 24234888 TI - Eco-Informa '96 : Global environmental communications. PMID- 24234889 TI - Preface. PMID- 24234891 TI - Intergovernmental panel on climate change : IPCC second assessment synthesis of scientific-technical information relevant to interpreting article 2 of the UN Framework Convention on Climate Change 1995. PMID- 24234890 TI - Guidelines for selection and application of fate and exposure models. AB - Guidelines for selection and application of fate and exposure models were developed as an instrument for the user to detect the most appropriate model for his/her special problem.Criteria for evaluating the quality and performance of implemented computer programmes and the underlying theory were defined.A model data bank for exposure models was developed which involves selection and quality characteristics; it was tested with ten randomly selected exposure models. PMID- 24234892 TI - Dioxin '95 : 15th international symposium on chlorinated dioxins and related compounds edmonton, alberta, Canada, august 21-25, 1995. PMID- 24234894 TI - Physical activity levels of cancer survivors in Canada: findings from the Canadian Community Health Survey. AB - PURPOSE: Physical activity may reduce many side effects of cancer treatment and may improve survival. The purpose of this analysis was to compare physical activity in cancer patients and survivors to those who have never had cancer and examine changes between 2005-2006 and 2009-2010. METHODS: Data were extracted from the 2005-2006 and 2009-2010 Canadian Community Health Survey. Respondents were asked whether they currently have or had cancer in the past and about physical activity. Based on duration and type of reported activity, respondents were classified as inactive, moderately active, or active. Logistic regression was used to assess the relationship between cancer history and physical activity. Differences in physical activity by survey cycle according to cancer status were also examined. RESULTS: After adjustment, respondents with cancer were more likely to be inactive than those who had never had cancer (OR = 1.39, 95 % CI 1.21-1.58, inactive vs. active), while individuals with previous cancer did not differ from population levels. The odds of being moderately active or inactive did not vary over time in those with current or previous cancer; however, respondents who had never had cancer were less likely to be moderately active or inactive in 2009-2010 (OR = 0.94, 95 % CI 0.92-0.96, inactive vs. active). CONCLUSIONS: Individuals with cancer are less likely to be active than those who have never had cancer, but those with a history of cancer have similar physical activity levels to population levels. Activity levels in all three groups are much lower than recommended. IMPLICATIONS FOR CANCER SURVIVORS: It is encouraging to note that those with cancer history are not less likely than the general population to be physically active. Individuals with a history of cancer have much to gain from participation in physical activity and health care providers should continue to encourage physical activity in accordance with published guidelines. PMID- 24234895 TI - Fluorescence studies on the conformation of litorin in solution and in the presence of model membranes. AB - The conformation of the nonapeptide hormone litorin has been studied in buffer and in the presence of lipids, using static and dynamic fluorescence. The results obtained show that, in buffer, the hormone probably exists in a collection of flexible conformers, slowly interconverting between them. The marked changes observed in fluorescence spectra and lifetimes upon addition of dimyristoylphosphatidylserine vesicles clearly show that the peptide interacts with lipids assuming lipid specific conformations. Interestingly, no significative spectroscopic changes are produced by exposure to dimirystoylphosphatidylcholine vesicles both in the gel and liquid-christalline phases, suggesting a requirement for negatively charged lipids during the process of hormone-membrane interaction. PMID- 24234896 TI - Fluorescence anisotropy and light-scattering studies of the interaction of insulin with liposomes. AB - The interaction between zinc-stabilized insulin and lecithin liposomal membranes was studied using DPH fluorescence anisotropy and light-scattering techniques. To ascertain a possible influence of a charge on the insulin molecule, experiments were performed at pH 4.5 (insulin possesses a positive charge) and at pH 7.4 (the charge of insulin is negative). Measurements at pH 4.5 revealed significant changes in scattered light intensity induced by the addition of insulin to lecithin liposomes. With increasing time of storage of liposomes the insulin effect became faster and more pronounced. At pH 7.4, significant changes in scattered light were registered only in the case of liposomes stored for 5 days. In these liposomes a peroxidation process of lecithin was revealed. No significant changes induced by insulin were observed in DPH fluorescence anisotropy either at pH 4.5 or at pH 7.4, which suggested the absence of an interaction of insulin with the hycrophobic core of liposomes. Thus, the observed changes in scattered light could be interpreted in terms of the insulin association to the liposomal surface in the case of phospholipid peroxidation and/or acidic pH. PMID- 24234897 TI - Nonenzymatic glycosylation of human serum albumin: Fluorescence and chemiluminescence behavior. AB - In the present study the progress of the cross-linking reaction between glyceraldehyde (GCA) and human serum albumin (HSA) was followed by monitoring the development of new absorption bands characteristic of the cross-linked product. Generation of electronically excited species (EES) during horseradish peroxidase (HRP)-catalyzed oxidation of glycosylated HSA was followed by measuring direct chemiluminescence. It was found that adducts of HSA with GCA in the presence of HRP are capable of forming EES. The mechanism of EES generation is discussed further on the basis of fluorescence and chemiluminescence measurements. Formation of EES in studied systems thus could be a possible source of free radicals generatedin vivo during age- and diabetes-related complications. PMID- 24234898 TI - Luminescence and anisotropy decays ofN-3-pyrene maleimide labeling IgG proteins and cells. AB - The Py.M (N-3-Pyrene Maleimide) is a dye that covalently binds to reactive amino or sulfhycryl groups to give highly fluorescent protein conjugates. Measurements of luminescence lifetimes and anisotropy decays have been performed with a Phase and Modulation Fluorometer. Complexes of Py.M-antibody (IgG antimouse) and tumoral cells C6 labeled with Py.M have been investigated. The Py.M fluorescence in buffer solution and the protein and cells natural fluorescence have been checked. For Py.M-IgG and labeled cells, the fluorescence decays present interesting behaviours. The least-squares analysis of the experimental results on Py.M-IgG complex points out two lorentzian distributions centered at 74 ns and 11 ns, on the contrary, for the labeled cells, a discrete component at 100 ns and a lorentzian distribution centered at 5 ns are shown. In both systems a weak component lower than 1 ns is observed. The fluorescence decays, mainly the long lifetime one, are very sensitive to oxygen quenching, showing the high efficiency of O2 quenching. For samples N2 bubbled, the lifetime experimental resuits show a decrease of the oxygen accessibility from free probe in solution to Py.M-IgG complex and to labeled cells, compatible with a more compact packing of the probe binding site. The experimental results of anisotropy decays of degassed samples show for Py.M-IgG complexes a long rotation correlation time of about 200 ns at T=5 degrees C, assigned to overall rotation of the protein, besides shorter correlation times attributable to inner protein motions. For labeled cells, the long rotation correlation time becomes of the order of 580 ns confirming a progressive increase of the stabilization of the binding site. PMID- 24234899 TI - The interaction of 4', 6-diamidino-2-phenylindole (DAPI) with pepsin. AB - We recently found that the fluorescent dye DAPI, well-known for its use with nucleic acids, is also able to interact with proteins as well as ordered phospholipids assemblies. The interaction of DAPI with pepsin under different conditions of pH and ionic strength was studied with fluorescence and circular dichroism techniques. From a comparison of the results obtained, the interaction appears to be rather tight and specific, dependent on both electrostatic and hydrophobic forces, and able to probe the tridimensional conformation of the protein. PMID- 24234900 TI - Intermolecular Foerster's energy transfer in labeled poly[N-(2 hydroxypropyl)methacrylamide]. AB - By copolymerization of monomers containing donor (carbazole) and acceptor (dansyl) fluorophores withN-(2-hydroxypropyl)methacrylamide (HPMA), statistical copolymers with "low" and "high" contents of the fluorophores were prepared. The increase in nonradiative energy transfer between copolymers with a low content of fluorophores was probably due to intermolecular penetration of the polymer coils in concentrated solutions. PMID- 24234901 TI - Pyrene excitation via resonance energy transfer from protein tryptophan reveals a fluidity gradient in liver microsomes. AB - Membrane fluidity measurements based on excimer formation of pyrene and pyrene derivatives as a measure of lateral diffusion yield a decreased fluidity in the presence of proteins [1,2]. It was the aim of our study to investigate whether the reduced excimer formation is due to a rigidifying effect of proteins on the whole membrane or if the fluorophore mobility is hindered mainly in the immediate protein environment. Resonance energy transfer in microsomal membranes between intrinsic tryptophan residues and pyrene was used to study the excimer formation rate in the vicinity of proteins. The excimer-to-monomer fluorescence ratio after excitation via resonance energy transfer decreased compared to that observed for the direct excitation. The results suggest that, because of the reduced fluidity in the neighborhood of proteins, pyrene and pyrenedodecanoic acid do not diffuse homogeneously in the membrane plane. PMID- 24234902 TI - Fluorescence staining of yeast cells permeabilized by killer toxin K1: Determination of optimum conditions. AB - Optimal assay conditions were established for the previously described method used to determine the activity ofSaccharomyces cerevisiae pore-forming killer toxin K1. The method is based on cell staining with bromocresol purple. Sensitive cells ofS. cerevisiae from the early exponential phase under nongrowth conditions and in the presence of glucose were the most convenient for determining the killer toxin activity. Maximum killing war reached when the suspension was buffered with 10 mM citrate-phosphate at pH 4.6. PMID- 24234903 TI - The frequency-domain method reveals the dimeric structure of Na,K-ATPase. AB - Lucifer yellow and lissamine rhodamine sulfonyl hydrazine were used as the donor and the receptor, respectively, for Forster energy transfer measurements to determine the location of the beta subunit in the native Na,K-ATPase from pig kidney. It was found that (1) the beta subunits are located in one functional complex, i.e., the dimer (alphabeta)2 appears to be the functional complex of Na,K-ATPase, and (2) the beta subunits in the functional enzyme complex in the membrane are not located next to each other but are rather well separated. The distance between fluorophores covalently attached to the beta subunits was found to be 5.3 nm. PMID- 24234904 TI - Fluorescence probes of viscosity: A comparative study of the fluorescence anisotropy decay of perylene and 3,9-dibromoperylene in glycerol. AB - The authors compare the results of fluorescence anisotropy decay measurements for glycerol solutions of perylene with those of 3,9-dibromoperylene (DBP). For both molecules a good linear dependence is observed between the glycerol viscosity (varied by temperature) and the longer rotational correlation time obtained as a result of a global (using data obtained at 256- and 430-nm excitation wavelengths) biexponential analysis of the fluorescence anisotropy decay, at least in the range of 7-60 P for perylene and 4-60 P for DBP. This significantly extends the reported range of 0.5 to 150 cP investigated by Williams and Ben Amotz [1] with the probe BTBP. PMID- 24234905 TI - Interaction of a phosphatidylcholine derivative of 1,6-diphenyl-1,3,5-hexatriene (DPH) with intact living cells: Steady-state fluorescence polarization and phase fluorometry studies. AB - The potential interest of DPH-PC was checked with a macrophagic cell line (P388D1). The uptake of DPH-PC was associated with a rapid increase in both fluorescence intensity and a slow decrease in anisotropy values. A flow cytometry comparative study with DPH revealed in both cases the existence of two cell subpopulations with different labeling levels. The analysis of fluorescence decay of DPH-PC showed two components. The fractional intensity of the main component (9.7 ns) is higher than 92%. The Lorentzian distribution of the main lifetime presents an important homogeneity. The observation that an increase in temperature induced a decrease in steady state anisotropy values but did not affect the lifetime suggests that the anisotropy variations effectively reflect modifications in the cohesion of probe micro-surroundings. A transmembrane diffusional phenomenon of a fraction of fluorescent phospholipids (205) was suggested by a study with a nonpermeant membrane quencher. The transmembrane diffusion was confirmed by extraction of the phospholipid analog with fatty acid free BSA. The use of inhibitors of endogenous phospholipase A2 showed a progressive hydrolysis of the fluorescent phospholipid. Nevertheless, the hydrolysis can be neglected in the case of short term interactions with cells (<30 min). Therefore, it can be assumed that DPH-PC can be used as a membrane probe. PMID- 24234906 TI - Influence of lipid composition and membrane curvature on fluorescence and solvent relaxation kinetics in unilamellar vesicles. AB - Time-resolved fluorescence on unilamellar vesicles shows that increasing amounts of anionic, natural lipid lead to a larger increase in polarity close to the headgroups than in the hydrophobic core of the bilayer. The region close to the headgroups is less polar in vesicles containing phosphatic acid rather than phosphatidylserine. A greater membrane curvature increases the mobility of the hydrated headgroups. PMID- 24234907 TI - Distribution of merocyanine 540 in phospholipid membranes. AB - The interaction of the fluorescent photosensitizer merocyanine 540 (MC-540) with model phospholipid membranes was studied. Two different-colored species (monomers and dimers) of MC-540 were registered in phospholipid liposomes. Variations in both phospholipid composition (DMPC, DPPC, POPC, egg PC) and temperature (15-60 degrees C) resulted in changes in the MC-540 monomerdimer distribution. The values of the monomer-dimer equilibrium constant of MC-540 in egg PC (K=14.8 MUM), in POPC (K=26.7 MUM), and in DMPC (K=271.0 MUM) were determined at the temperature of 23+/-2 degrees C. Suppression of MC-540 association with phospholipid bilayers was provoked by the addition of albumin to a liposome suspension. Albumin was observed to compete very successfully with lecithins containing saturated fatty acid chains (DPPC, DMPC), while only a weak competition of albumin with unsaturated lecithins (POPC, egg PC) for binding MC 540 molecules was registered. PMID- 24234908 TI - Absolute spectroscopic determination of cross-membrane potential. AB - Spectroscopic determination of the cross-membrane electric potential has been used for more than 20 years. This method, which usually employs absorption or fluorescence measurements, allows for a rapid and noninvasive study of the electrical properties of the membranes of cells and liposomes. However, the usual fluorescence techniques preferably allow monitoring changes in the potential on triggerable or excitable membranes, and not the absolute value of the potential. They also do not provide means for measuring the potential on single cells. This paper reviews three methods that solve these issues. Nernstian dyes which partition between intra-and extracompartmental volumes enable a fluorescence microscopic determination of a single cell and even a single organelle. Dual wavelength ratiometric recording from membrane-staining dyes also provides means for measuring the field on a single cell. Resonance Raman probes provide a spectroscopic method with a natural internal standard for the absolute measurement of membrane potential. PMID- 24234909 TI - On the interpretation of fluorescence anisotropy decays from probe molecules in lipid vesicle systems. AB - Measurements of fluorescence depolarization decays are widely used to obtain information about the molecular order and rotational dynamics of fluorescent probe molecules in membrane systems. This information is obtained by least squares fits of the experimental data to the predictions of physical models for motion. Here we present a critical review of the ways and means of the data analysis and address the question how and why totally different models such as Brownian rotational diffusion and "wobble-in-cone" provide such convincing fits to the fluorescence anistropy decay curves. We show that while these models are useful for investigating the general trends in the behavior of the probe molecules, they fail to describe the underlying motional processes. We propose to remedy this situation with a model in which the probe molecules undergo fast, though restricted local motions within a slowly rotating cage in the lipid bilayer structure. The cage may be envisaged as a free volume cavity between the lipid molecules, so that its position and orientation change with the internal conformational motions of the lipid chains. This approach may be considered to be a synthesis of the wobble-in-cone and Brownian rotational diffusion models. Importantly, this compound motion model appears to provide a consistent picture of fluorescent probe behavior in both oriented lipid bilayers and lipid vesicle systems. PMID- 24234910 TI - Effect of dietary bovine colostrum on the responses of immune cells to stimulation with bacterial lipopolysaccharide. AB - Previous studies have revealed that ingestion of bovine colostrum is effective in preventing pathogens from invading through the gastrointestinal tract (GI) and modulating the mucosal immunity of the GI tract, indicating that its effect is principally local. Thus it is unclear if ingestion of bovine colostrum can affect the systemic immune system. In this study, we investigated the effect of taking bovine colostrum (vs phosphate-buffered saline) for 14 days on the behavior of the immune cells of mice. Isolated splenocytes, which are pivotal cells of systemic immunity, were then stimulated with Escherichia coli lipopolysaccharide. Bovine colostrum significantly reduced NK cell and monocyte activities and lymphoproliferaltive responses to LPS stimulation. Thus dietary bovine colostrum renders immune cells less responsive to LPS stimulation. Dietary bovine colostrum thus affects the systemic immune system and may have anti-inflammatory actions. PMID- 24234911 TI - Carbon-based drug delivery carriers for cancer therapy. AB - In the search to improve anticancer therapies, several drug carriers, including carbon-based nanomaterials have been studied. Both liposomes and polymeric microspheres have been used in anticancer drugs. However, there remains an on going need for better therapeutic materials that have good drug solubility, an ability to reduce systemic toxicity through specific-tumor targeting, and rapid clearance. In this regard, carbon allotropes such as graphene oxide (GOs), carbon nanotubes (CNTs), and nanodiamonds (NDs), have been investigated, as they possess sufficient surface-to-volume ratio, thermal conductivity, rigid structural properties capable of post-chemical modification, and excellent biocompatibility. This review is aimed at exploring these carbon-based nanomaterials for use as multifaceted cancer drug carriers and is intended to demonstrate that GOs, CNTs, and NDs are likely to improve chemotherapeutical strategy for cancers in either a sole or combinational manner. PMID- 24234912 TI - G-protein coupled receptor 40 agonists as novel therapeutics for type 2 diabetes. AB - With growing needs for new antidiabetic drugs which are safe and effective alone or in combination with existing drugs, G-protein coupled receptor 40 (GPR40) has drawn a considerable attention as a potential therapeutic target for type 2 diabetes. As GPR40 agonist may offer advantages to commonly used agents, by acting ambient glucose dependent manner which mechanistically leads to reduced risk of developing hypoglycemia. Since deorphanization in 2003, development of small molecule GPR40 agonists has been spurred by several research groups. There are a number of lead molecules targeting GPR40, and among these molecules TAK-875 (full agonist) and AMG 837 (partial agonist) advanced into clinical stage. PMID- 24234913 TI - Therapeutic applications of electrospun nanofibers for drug delivery systems. AB - Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release. PMID- 24234914 TI - Antiplatelet, anticoagulant, and profibrinolytic activities of cudratricusxanthone A. AB - Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau, is known to possess hepatoprotective, antiproliferative and anti-inflammatory activities. However, antiplatelet, anticoagulant, and profibrinolytic properties have not been studied. The anticoagulant activities of CTXA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), and the activities of cell based thrombin and activated factor X (FXa). The effects of CTXA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-alpha (TNF alpha) activated human umbilical vein endothelial cells. Our data showed that CTXA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. CTXA prolonged in vivo bleeding time and inhibited TNF-alpha induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by CTXA. Collectively, these results indicate that CTXA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. PMID- 24234915 TI - A neuroinformatics of brain modeling and its implementation in the Brain Operation Database BODB. AB - We present principles for an integrated neuroinformatics framework which makes explicit how models are grounded on empirical evidence, explain (or not) existing empirical results and make testable predictions. The new ontological framework makes explicit how models bring together structural, functional, and related empirical observations. We emphasize schematics of the model's operation linked to summaries of empirical data (SEDs) used in both the design and testing of the model, with tests comparing SEDs to summaries of simulation results (SSRs) from the model. We stress the importance of protocols for models as well as experiments. We complement the structural ontology of nested brain structures with a functional ontology of Brain Operating Principles (BOPs) for observed neural function and an ontological framework for grounding models in empirical data. We present an implementation of this ontological framework in the Brain Operation Database (BODB), an environment in which modelers and experimentalists can work together by making use of their shared empirical data, models and expertise. PMID- 24234916 TI - Action and language mechanisms in the brain: data, models and neuroinformatics. AB - We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding - separately or together - neurocomputational models and empirical data that serve systems and cognitive neuroscience. PMID- 24234917 TI - Potential of a cyclone prototype spacer to improve in vitro dry powder delivery. AB - PURPOSE: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. METHODS: Cyclohaler(r), Accuhaler(r) and Easyhaler(r) were tested with and without the spacers between 30 and 60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. RESULTS: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 +/- 6.51% at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler(r) at 4 kPa: 1.08 +/- 0.05 MUm vs. 3.00 +/- 0.12 MUm, with and without Cheng 2, respectively) and unaltered with increased flow rates. CONCLUSION: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery. PMID- 24234918 TI - Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach. AB - PURPOSE: To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. METHODS: Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in amodel SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. RESULTS: Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion was observed and predicted by the developed model. Ninety minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. CONCLUSION: A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID- 24234919 TI - The sales of lottery tickets to minors in Illinois. AB - Fifty retail outlets were tested with a 16-year-old girl in eight central Illinois cities to determine the willingness of retail clerks to illegally sell a lottery ticket to a minor. A total of 49 establishments or 98% sold. In two instances the youth was denied access to cigarettes but sold a lottery ticket despite the sales of both to a minor under age 18 being illegal in Illinois. A very low cost method of correcting the problem is presented. PMID- 24234920 TI - The gambling lifestyle: II. Treatment. AB - Two individuals with records of prior compulsive gambling involvement are profiled in order to illustrate the nature of a gambling lifestyle and describe the process of lifestyle change. The treatment model utilized by therapists proposing a lifestyle interpretation of compulsive gambling behavior is guided by three primary objectives or goals: (1) the cessation of lifestyle activities; (2) the development of skills useful in managing gambling-related conditions, choices, and cognitions; and (3) the implementation of an effective program of follow-up intervention and support. These goals give rise to the three stages of lifestyle intervention - (1) laying a foundation for change, (2) identifying vehicles for change, and (3) establishing a reinforcing nongambling life-style from which specific change strategies are derived. The implications of this model and the possibility of limited generalizability are discussed. PMID- 24234921 TI - Casino gaining offense inmates: What are these men like? AB - The characteristics of 28 men convicted for casino gaming offenses in Nevada were determined. Twenty-seven of these inmates cheated using slot or video poker machines. Most of the subjects used slugs. The other cheated at cards. Compared to other inmates, a disproportionate number of inmates were white. There were no black inmates incarcerated for this crime. Eighteen (57%) of the gaming offenders were over the age of 40 when convicted, in significant comparison to 27% of the general population inmates. They had significantly more aliases than the general population inmates. None of the gaming offenders had a history of violent felony convictions. They had, however, a history of great social, marital, occupational, and financial instability in addition to a criminal life style. PMID- 24234922 TI - Really not god: Secularization and pragmatism in Gamblers Anonymous. AB - The paper argues that despite maintaining the image of a twelve-step organization, the central theme of the history of Gamblers Anonymous (GA) in the United States is the increasing secularization of the program of the recovery. The paper documents the increasing secularization and pragmatism of Gamblers Anonymous, as reflected in key documents, despite the spiritual vision of its founding member. The author speculates on why Gamblers Anonymous took a secularized development path. Further research is called for. PMID- 24234923 TI - The development of pathological gambling in Sweden. AB - The development and the social, psychological and cultural conditions of pathological gambling reported by 42 interviewed pathological gamblers were compared with data from 63 pathological gamblers identified by case-finding. The two studies gave similar results. Gambling on horse races, roulette and bingo were the only types showing a progressive increase in involvement over time. When gambling heavily 40% of the pathological gamblers regularily experienced a state of altered consciousness. When abstaining from gambling withdrawal-like symptoms were experienced by a third. Fifty-two percent reported at least one family member often gambling. Pathological gambling appears to be a secret behaviour, although there are collective features in its development. PMID- 24234924 TI - Social, psychological and physical consequences of pathological gambling in Sweden. AB - Social, psychological and physical consequences of pathological gambling reported by 42 pathological gamblers recruited mainly by advertising were compared with data on 63 pathological gamblers identified by case-finding within districts of probation, in- and out-patient psychiatric care and social welfare authorities. The two studies gave similar results. Financial breakdown, impaired relations with family and friends, and psychological problems occurred in about 50% of the pathological gamblers. Physical consequences were perceived to be of minor significance. Gambling became a solitary behavior as illegal behaviors to finance gambling increased. The pathological gamblers frequently abused alcohol. Despite these signs of social decay the pathological gamblers strove not to be a burden in society. PMID- 24234926 TI - Editorial comment: Optimizing rehabilitation. PMID- 24234925 TI - Beating the fruit machine: Systems and ploys both legal and illegal. PMID- 24234927 TI - Does knowledge of a patient's workers' compensation status influence clinical judgments? AB - It is generally acknowledged that compensation payments (WCB) influence rehabilitation outcome in a negative manner. Patients receiving WCB have more treatment over a longer time period than their non compensated (NWCB) cohorts. It is not clear whether therapists (PT) perceive WCB clients as being more impaired and expect them to have a worse outcome than clients without WCB. The purpose of this study was to determine whether PTs' clinical judgments are influenced by the knowledge of a patients WCB status and whether this knowledge influences their assessment findings or prognostic judgments. A convenience sample of 69 physical therapists (PTs) participated. Each PT viewed three videotaped assessments, of patients with low back pain (LBP) that differed in severity. The PT was provided with a brief history of the patient. Included in the history was a statement that the patient was (WCB group), or was not (NWCB group) in receipt of workers compensation benefits (WCB). The third group of PTs was given no information (control group) about the patient. PTs recorded physical assessment findings and made prognostic judgments about the patients. Data for the physical assessment findings and prognoses recorded by the PTs was analyzed across information groups using ANOVA. Knowledge of compensation status did not influence the PTs' physical assessment findings but did influence prognostic judgments. WCB status was deemed to have a negative effect on outcome in patients with mild LBP. Additionally, NWCB status was deemed to have a positive influence on outcome in patients with severe LBP. The differences were most marked in the short term (1 month). It was concluded that PTs expectations of outcome are influenced by prior knowledge of compensation status. PMID- 24234928 TI - Required thermal environments for the quadriplegic persons: Analyses of questionnaires and experiments on their daily life. AB - A physically disabled person often has additional disabilities on adaptation to the thermal environment. Since 1976, our group has carried out a series of studies to find required thermal conditions for disabled persons on several typical disabilities. This paper reports on the results of our latest questionnaire and experiments on daily thermal environment for quadriplegic persons. Among 292 quadriplegic persons with valid questionnaire, 184 (63%) were fully paralyzed. Nearly 90% of these and 60% of partially paralyzed patients were dissatisfied with the thermal environment and sweating. Several suggestive differences were found according to the broken positions of vertebrae. The results of 48 hours of field measurements on three quadriplegic subjects are compared with those obtained from questionnaire. PMID- 24234929 TI - The use of films to simulate age-related declines in yellow vision. AB - One of characteristics of normal age-related vision losses depends on yellow intensity in the lens of the eye. (1) We investigated discrimination between seven intensities of yellow in 303 elderly people aged from late 60s to early 90s. The results demonstrated that the failures of vision increase with age, and the losses depend on yellow intensity. (2) We got a yellow index (YI) from different Y-intensity color charts used in (I) above, covering 12 kinds of marketable yellow films, and selected two kinds of films which match (YI) original color charts, corresponding to 53% or 89% of Y intensity. (3) Finally, we judged that all of these colors' xy-chromaticities with or without the two films, were exactly on the unique-yellow line in the diagram, which means a pure yellow, not mixed. (4) Then, these two films could simulate each of the mid-level or high-level Y intensity, respectively, in age-related vision. (5) We analyzed changes of all kinds of colors (220) in xy-chromaticity diagrams and obtained mean changing distances from every original chromatogram compared to the others. These data would be useful for architects or designers to design cities or buildings for use by the elderly. PMID- 24234930 TI - A domestic assistive device for rheumatoid hands. AB - A domestic aid capable of squeezing water from a dishcloth is currently not available and such a task is performed in most households. The need for such a device was investigated. To establish the need, 54 rheumatoid arthritis patients were surveyed through a structured questionnaire for hand impairment and difficulty in this task. While 27% of the participants reported normal hand ability, 28% had minimal impairment, 39% moderate impairment, and 7% severe impairment. Sixty-one percent reported having difficulty with their hands and wrists. The mobility deficit was the cause of difficulty among 59%, and strength deficit in 80%. Ninety-three percent of patients had difficulty due to pain. The activity was avoided by 43%. If a device was available, 74% would use it. A water squeezing device was designed and a prototype fabricated which eliminated finger and wrist stress in this task. PMID- 24234931 TI - Match analysis and player characteristics in rugby sevens. AB - Rugby sevens is a contact sport contested by two teams of seven players who compete over two 7-min halves, most frequently played in a tournament style. The IRB Sevens World Series is thought of as the preeminent rugby sevens competition in the world and has grown in competitiveness from its inception in 2000. The decision to include rugby sevens in the 2016 Olympics is likely to increase the global profile and participation in the game. Many rugby sevens players concurrently compete in 15-a-side rugby union as backs and loose forwards; however, a continued increase in the popularity of rugby sevens will likely see the emergence of the specialist rugby sevens player. Often thought of as the abbreviated version of rugby union, rugby sevens is played under nearly identical laws and on the same field dimensions as the 15-man code. However, research has shown the movement demands of rugby sevens and rugby union are dissimilar, with rugby sevens players spending a larger proportion of the game running at high intensity (>= 5 m s(-1)). Given the dissimilarity in match demands in conjunction with differences in the competition structure between the codes, it appears the considerable depth of literature specific to performance in rugby union may be of little value for the preparation of rugby sevens players. Investigations of the physical characteristics of rugby sevens players show backs are lighter and shorter than forwards, while players across all positions possess a lean body composition. International rugby sevens players have similar speed characteristics to rugby union backs across distances of 10-30 m; however, rugby sevens players appear to have superior intermittent aerobic endurance. Despite being of likely importance, little is known of the strength and power characteristics of rugby sevens players. Research into the speed and aerobic endurance characteristics of rugby sevens players has not distinguished between backs and forwards and, as such, it is unclear whether differences exist between the position groups. PMID- 24234932 TI - Association Between Catechol-O-Methyltransferase (COMT) Gene Polymorphisms, Parkinson's Disease, and Levodopa Efficacy. AB - OBJECTIVES: We investigated the association between catechol-O-methyltransferase (COMT) gene polymorphisms and Parkinson's disease (PD) susceptibility, severity of disease, and levodopa (L-Dopa) efficacy. SUBJECTS AND METHODS: Patients (N = 97) with primary PD and healthy volunteers (N = 102) were recruited. Disease severity was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn & Yahr grade at 'On stage'. Genomic DNA was extracted from blood cells. Polymerase chain reaction and sequencing were used to detect COMT mutations. Data were analyzed by SPSS 18.0. False discovery rate (FDR) or Bonferroni correction was used if the result showed P < 0.05. RESULTS: Four COMT mutations were detected in 199 subjects: rs74745580 (only in two patients with primary PD), rs4633, rs6267, and rs3838146. There were no statistical differences in frequencies of rs4633, rs6267, and rs3838146 genotypes between PD patients and the control group. The frequency of allele rs4633T was higher in PD patients than in the control group. UPDRS score was lower in rs4633 (CT/TT) carriers and rs3838146 (-C/- -) carriers than in rs4633 (CC) and rs3838146 (CC) carriers. PD patients carrying rs6267 (GT/TT) had higher UPDRS scores than patients with rs6267 (GG) (P < 0.05). The frequencies of the three polymorphisms were not statistically different between patients who did and did not receive L-Dopa; dose and duration of L-Dopa treatment did not differ between genotypes; and there was also no difference in the ratios of loss of efficacy towards levodopa. CONCLUSIONS: The polymorphisms rs4633, rs6267, and rs3838146 were associated with severity of PD but were not associated with L-Dopa medication. PMID- 24234933 TI - Early gas chromatography/mass spectrometry. AB - Spectroscopy Laboratory, The Dow Chemical Company, Midland, Michigan, USA In December 1955 or thereabouts, the authors coupled a homemade gas chromatograph to a research time-of-flight mass spectrometer constructed by W. C. Wiley, I. H. McLaren, and D. B. Harrington. This unique gas chromatography/mass spectrometry (GC/MS) instrument generated mass spectra at a lo-kHz rate for display on an oscilloscope; eluted gas chromate graphic components, such as methanol, acetone, benzene, toluene, and carbon tetrachloride, could be visually identified immediately from the oscilloscope display. Many years of further research and development in many laboratories worldwide were necessary, however, to make continuous on-line GC/MS the uniquely valuable analytical tool that it is today. PMID- 24234934 TI - A new mass spectrograph. AB - The optical designs of two new types of mass spectrographs were studied. The first is a system that possesses a specially shaped magnet output boundary to satisfy the double-focusing condition for a wide mass range. The focal plane is usually curved. The second system is one in which a parallel ion beam is generated before the magnet, forming a straight double-focusing line. By introducing a quadrupole lens doublet such that the ion beam may be deflected in the same direction through the electric and magnetic fields, the overall image magnification can be arbitrarily controlled and stigmatic focusing achieved for the median ray. PMID- 24234935 TI - An improved ion guide for external ion injection in glow discharge—fourier transform ion cyclotron resonance mass spectrometry. AB - To improve the existing ion transport optics of our glow discharge (GD)-Fourier transformion cyclotron resonance (FT-ICR) mass spectrometer, we simulated several ion trajectories between the GD source region and the ICR analyzer cell. These calculations suggested that a number of simple improvements, including the use of an ion flight tube and an electrically isolated conductance limit, would increase the efficiency of ion transfer through the fringing fields of the FT-ICR superconducting magnet and into the ICR analyzer cell. Ion beam intensity was monitored as a function of the distance between the GD source and the analyzer cell before and after implementing these improvements. A twentyfold improvement in the transport efficiency, as well as a fifteenfold enhancement in detected ET ICR signals, was observed. PMID- 24234936 TI - Gas-Phase cationization and protonation of neutrals generated by matrix-assisted laser desorption. AB - The ionization mechanisms involved in matrix-assisted ultraviolet laser desorption/ionization (MALDI) were studied with a time-of-flight mass spectrometer. When protonated or cationized quasimolecular ions generated by MALDI are not extracted promptly, their abundance is a function of the delay time between laser irradiation and ion extraction, maximizing at an optimum delay time (DTM) of a few hundred nanoseconds. The ion abundance at DTM exceeds that of prompt extraction by a factor of 2 or more. Increasing the cation density near the sample surface reduces the DTM, whereas increasing the desorption laser irradiance has the opposite effect. The enhancement suggests extensive gas-phase ion-molecule reactions after irradiation by the desorption laser has ceased. PMID- 24234937 TI - Matrix-assisted laser desorption ionization mass spectrometry with 2-(4 hydroxyphenylazo)benzoic acid matrix. AB - A novel matrix substance, 2-(4-hydroxyphenylazo) benzoic acid, or HABA, has been found to be very advantageous for matrix-assisted ultraviolet laser desorption ionization mass spectrometry. This compound has been successfully used for the desorption of peptides, proteins, and glycoproteins up to approximately 250 kDa. For these materials, the most abundant analyte-related peaks correspond to [M + H](+) ions and multiply protonated molecules. Comparisons with sinapic acid, 2,5 dihydroxybenzoic acid, and alpha-cyano-4-hydroxycinnamic acid indicate that the new matrix provides comparable sensitivity for peptides and smaller proteins but results in better sensitivity for larger proteins and glycoproteins in protein mixtures. Other matrices discriminate against the higher mass components in these cases. Somewhat reduced mass resolution has been found for smaller proteins, but for larger proteins and glycoproteins the best mass resolution can often be obtained with the new matrix. For other classes of compounds that form ions predominantly via cation attachment, at least as good sensitivity and even better resolution have been obtained. Derivatized glycolipids and synthetic polymers have been studied in detail. For the analysis of many synthetic polymers, the best performance in terms of sensitivity and mass resolution has been observed with HABA matrix. Mass resolution was higher for cation adducts than for the protonated peptide molecules in the same mass range. The new matrix exhibits greatly extended (in time) analyte ion production and reproducibility. Owing to the uniform sample surface with this matrix, barely any spatial variation of the ion signal could be observed. In addition, many hundreds of single-shot mass spectra could be accumulated from the same spot, even for larger proteins. PMID- 24234938 TI - Role of ion-ion recombination for alkali chloride cluster formation in liquid secondary ion mass spectrometry. AB - Liquid secondary ionization mass spectra of solutions of alkali chlorides in glycerol were studied as a function of salt concentration. The experimental abundances of glycerol ions and of Cs(+)(CsCl) n cluster ions were successfully reproduced by assuming that most of the randomly distributed ions pair up with counterions shortly after impact. Further, it is considered that clustering (or proton transfer) reactions occur mainly between an ion that survives the pairing process and ion pairs (or basic analytes) in the immediate vicinity; however, some mixing undoubtedly occurs in the later stages of the desorption process. At the density of the original matrix, the range of proton transfer is calculated to be 5-15 A, and that of clustering approximately 25% shorter. These reaction distances are inversely correlated with the internal energy of the ejected ions. In general, liquid secondary ionization mass spectra of alkali chloride solutions can be seen to result from competitive ion-ion recombination reactions in the decaying matrix. Finally, from the abundances of cluster ions containing [glycerol - H](-) ions, it is estimated that approximately 1% of the glycerol molecules in the ejected volume are ionized in the collision cascade. PMID- 24234939 TI - Doped gelatin films as a model matrix for molecular secondary ion mass spectrometry studies of biological soft tissue. AB - Porcine gelatin films doped with a number of biological compounds at various concentrations and prepared by spin-casting have been used as model biological tissue matrices for studying organic ion emission in molecular secondary ion mass spectrometry. For many compounds, portions of the working curves were found to be linear over several orders of magnitude in concentration. Detection limits for the, analyzed compounds were in the parts per million range for several organic salt compounds but high (0.1 wt%) for others. Owing to the presence of a significant chemical background, the poorest detection limits were generally obtained from compounds with low molecular weights. Secondary ion yield matrix effects, indicated by a reduction in ionization efficiency at higher concentrations, were observed for several organic salt compounds. PMID- 24234940 TI - Identification of a new fragment ion type in the collision-induced dissociation spectra of peptides: Formation of a2-16 ions. AB - The identification of an ion observed in the high-energy collision-induced dissociation spectra of several model peptides is reported. The ion, observed at m/z 99 for the peptide pentaalanine (Ala5) and designated a2-16, is shown to have an elemental formula of C5H9NO by high-resolution peak matching. The precursor ion spectrum of the a2-16 ion and product ion spectra of the a2 and the a2+ 1 ions for Ala5 suggest that this ion is formed by the loss of 17 u (presumably NH3) from the a2+1 ion and, to a lesser extent, by loss of 28 u (presumably CO) from the b2-16 ion. On the basis of the data presented and other experimental evidence, a structure and mechanism for the formation of the a2-16 ion is proposed. PMID- 24234941 TI - Erratum to: J. Am. Soc. Mass Spectrom. PMID- 24234942 TI - Outcomes of a patient recall following early failure of hip hemiarthroplasty. AB - BACKGROUND: Unexpected early loosening was noted in some patients who had bipolar hemiarthroplasties using aspecific combination of head and stem. AIM: A review of all patients who had received this implant combination was performed to establish whether there was a higher than expected failure rate and to identify those patients who had evidence of early loosening requiring further intervention or monitoring. METHODS: Theatre records were reviewed to identify those who had undergone bipolar hemiarthroplasty using these products. All surviving patients were contacted and offered an appointment at which they underwent clinical and radiological review. Following review, revision rates were compared to published Australian joint registry data. RESULTS: Of 247 eligible for recall, 139 attended for clinical and radiological review. The cumulative revision rate was 6.8 % at 4 years, with a mean time to revision of 26 months; however, there was a significantly higher revision rate of 12.1 % in those aged under 75 years at the time of surgery (p = 0.01). This is significantly higher than rates quoted for bipolar hemiarthroplasties in Australian joint registry data. CONCLUSION: Overall, higher than expected revision rates due to early loosening were seen for this product combination,especially in patients aged?75 years at the time of the initial surgery. PMID- 24234943 TI - Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine. AB - OBJECTIVE: To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. CASE SUMMARY: A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol/L, serum osmolality was 263 mosmol/kg, urine osmolality 410 mosmol/kg and urine sodium 63 mmol/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol/L during treatment with mirtazapine. DISCUSSION: SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. CONCLUSIONS: Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary. PMID- 24234944 TI - Medication reconciliation by a pharmacy technician in a mental health assessment unit. AB - BACKGROUND: Medication discrepancies are common when patients cross organisational boundaries. However, little is known about the frequency of discrepancies within mental health and the efficacy of interventions to reduce discrepancies. OBJECTIVE: To evaluate the impact of a pharmacy-led reconciliation service on medication discrepancies on admissions to a secondary care mental health trust. SETTING: In-patient mental health services. METHODS: Prospective evaluation of pharmacy technician led medication reconciliation for admissions to a UK Mental Health NHS Trust. From March to June 2012 information on any unintentional discrepancies (dose, frequency and name of medication); patient demographics;and type and cause of the discrepancy was collected. The potential for harm was assessed based on two scenarios; the discrepancy was continued into primary care, and the discrepancy was corrected during admission. Logistic regression identified factors associated with discrepancies. MAIN OUTCOME MEASURE: Mean number of discrepancies per admission corrected by the pharmacy technician. RESULTS: Unintentional medication discrepancies occurred in 212 of 377 admissions (56.2 %). Discrepancies involving 569 medicines (mean 1.5 medicines per admission) were corrected.The most common discrepancy was omission(n = 464). Severity was assessed for 114 discrepancies. If the discrepancy was corrected within 16 days the potential harm was minor in 71 (62.3 %) cases and moderate in 43(37.7 %) cases whereas if the discrepancy was not corrected the potential harm was minor in 27 (23.7 %) cases and moderate in 87 (76.3 %) cases. Discrepancies were associated with both age and number of medications; the stronger association was age. CONCLUSIONS: Medication discrepancies are common within mental health services with potentially significant consequences for patients.Trained pharmacy technicians are able to reduce the frequency of discrepancies, improving safety. PMID- 24234945 TI - Attitudes towards conscientious objection among community pharmacists in Poland. AB - BACKGROUND: The European Council Resolution 1763 (2010), ''The right to conscientious objection in lawful medical care'', provoked a discussion among Polish pharmacists on the necessity for granting them the right to refuse to dispense medicinal products which invoke conscientious objection. OBJECTIVE: To explore attitudes of Polish pharmacists towards the conscience clause. SETTING: Pharmacies with public e-mail addresses in various parts of Poland (Lower Silesia Province, Mazovia Province, Kuyavia-Pomerania Province, and West Pomeranian Province). METHOD: An online survey questionnaire addressed to 1,454 pharmacies. The participants were asked 8 questions,including a question addressed only to pharmacy managers and owners. MAIN OUTCOME MEASURE: Attitudes towards the right to conscientious objection for pharmacists. RESULTS: Ultimately, responses of 126 pharmacists (83 women, 43 men, average age-39 years of age) were taken into consideration. Most participants (92 %) have never refused to fill a prescription due to their beliefs; however, 15 % of participants state that if the conscience clause were legally sanctioned, they would exercise this right. Most participants(73 %) think that pharmacists should not have the right to conscientious objection. Almost half of participants who support implementation of the conscience clause would grant this right to pharmacists on a conditional basis, if the pharmacists were obliged to present other real options to the patient about obtaining a specific product. CONCLUSION: Pharmacists are rather reluctant to the idea of implementing the conscience clause, but despite a clear majority of its opponents, there seems to be a necessity for introducing such a regulation. PMID- 24234947 TI - The internet: Can you live without it? PMID- 24234946 TI - Standard and Novel Treatment Options for Metabolic Syndrome and Diabetes Mellitus. AB - OPINION STATEMENT: Type II diabetes and metabolic syndrome are 2 intertwined conditions that are critical to the healthcare landscape in the United States and abroad. Patients with either diabetes or metabolic syndrome can have a dramatically increased risk of developing cardiovascular disease. Numerous treatment options have existed for some time, which include nonpharmacologic and pharmacologic therapies. In addition, within the last decade, a multiple of novel treatment options have emerged for the management of hyperglycemia in particular. By targeting novel pathways beyond the secretion and supply of insulin, these new therapeutics provide a valuable adjunct to the currently available therapies for diabetes and metabolic syndrome. Here we discuss the current guideline-driven usage of standard therapies with some novel indications. In addition, we discuss the novel therapies for the treatment of hyperglycemia, their mechanisms of action, and appropriate therapeutic indications. PMID- 24234948 TI - Behavioural early warning responses to polluted water : Performance ofGammarus pulex L. (Crustacea) andHydropsyche angustipennis (Curtis) (Insecta) to a complex industrial effluent. AB - Behavioural early warning responses to polluted surface water from an industrial effluent have been measured in two freshwater macroinvertebrate species using the four electrode impedance conversion technique. Specimens ofGammarus pulex (L.) andHydropsycho angustipennis (Curtis) were caught from reference streams and exposed to water from above and below the factory and to reference water for about 1 h with different kinds of behaviour being registered on-line every 10 min, such as time spent on locomotion, number of "high swimming peaks", number of activity phases, cleaning, time spent on ventilation, ventilation frequency and netspinning. Additionally, G.pulex was exposedin situ above and 100 m, 500 m and 1000 m below the factory for 24 h.G.pulex reacted to water pollution within 1 h with less time spent on locomotion, fewer "high swimming peaks" and lower number of activity phases (p < 0.01). The same results were found after thein situ exposure (p < 0.05) and the pollution gradient mirrored survival and behavioural performance of the organisms.H. angustipennis reacted to water pollution within 1 h with decreased time spent on ventilation (p < 0.001), no change in locomotion and netspinning during daytime. During the night, exposure to water pollution resulted in increased locomotion (p < 0.0001).Simultaneous multispecies on-line biomonitoring of industrial effluents is recommended for reliable risk assessment. PMID- 24234949 TI - Monitoring behavioural responses to metals in gammarus pulex (L.) (Crustacea) with impedance conversion. AB - An impedance conversion technique was used to study the behaviour of Gammarus pulex (L.) exposed to acutely toxic concentrations of Pb (0.01, 0.05, 0.1 and 0.5 mg Pb 1(-1)) and to field concentrations of Cu (<= 0.05 mg Cu 1(-1)). Initial stress responses were studied during short-term exposure (1 h), and sublethal toxic effects were monitored during 7 (Pb) and 35 days (Cu), respectively. Exposure to Pb caused 30 % mortality and resulted in a bioconcentration factor (BCF) of 2700 at 0.5 mg Pb l(-1) after 168 h. Exposure to Cu polluted stream water caused no mortality within 35 days, and uptake was low (BCF 5.8). Gammarus pulex reacted with initial stress responses to metal exposure within 30 min (Cu) or 1 h (Pb). The reactions consisted of increased ventilation and decreased locomotion.Sublethal concentrations of Pb and Cu caused toxic effects on the behaviour of G. pulex after several days of exposure, consisting of increased ventilation and decreased locomotion.Impedance conversion is an appropriate method for detecting stress responses to metals and can be used in "early warning" biomonitoring systems as well as for acute and chronic behavioural toxicity testing. PMID- 24234950 TI - Biotransformation of halogenated benzenes in anaerobic sediments. AB - The transformation kinetics of halogen substituted benzenes was examined in estuarine sediment. The sediment was sulfidogenic with sulfate concentration of 20 mmole/l. All compounds transformed without any lag period, with rate constants between 0.0016 and 0.0342 day(-1) or half-lives of 20 and 433 days. For the compounds with different halogen substituents on the aromatic ring, the transformation rate of the compound decreased in the order: I s> Br s> Cl s> F. PMID- 24234951 TI - Toxic oxide deposits from the combustion of landfill gas and biogas. AB - Oxide deposits found in combustion systems of landfill gas fired power stations contain relatively high concentrations of elements which form volatile species such as P, As, Sb and Sn. These deposits should be handled with care because of their potential toxicity. By contrast, deposits in biogas system engines were found to contain much lower levels of such elements. The enrichment of these elements can be attributed to a hypothetical multistage process. The elements form volatile species in the landfill body. They are selectively transported as part of the landfill gas into the gas-burning devices. Inside the burners, they are immobilized as nonvolatile oxides. PMID- 24234952 TI - Hazard assessment of chemicals in soil : Proposed ecotoxicological test strategy. AB - Based on a stepwise (tiered) approach, degradation, adsorption and leaching tests as well as various effect tests (using plants, microorganisms and animals) are recommended for the testing of environmental chemicals. If, after the tests of tiers 1 and 2, the results of a monospecies-effect-test (including a safety factor) are within the range of the predicted exposure, the ecotoxicological hazard should be determined using a terrestrial model ecosystem. Some of the tests for the proposed strategy were selected from practical experience in testing environmental chemicals in the laboratory, and some on the basis of a comprehensive literature review. PMID- 24234953 TI - Contaminants of food : Prioritisation scheme to identify manufactured organic chemicals as potential contaminants of food. AB - A scheme has been developed to rank 70 industrial organic chemicals in order of their priority for further study as potential contaminants of food. Numerical scales were developed for the following seven key criteria concerning environmental issues, food and toxicity: -Production volume -Pattern of usage Possible fate in the environment -Likelihood of chemical entering the food chain Mechanism of entry into the food chain -Persistence and accumulation in the food chain -Toxicity. Each chemical was assigned a score for the above criteria, which were combined to give an overall ranking for the chemicals.This scheme has been endorsed by the MAFF Steering Group on Chemical Aspects of Food Surveillance. It will be used in the assessment of relative priorities for further non-statutory surveillance for these contaminants in the UK food supply. PMID- 24234954 TI - Food irradiation : After 30 years, where do we stand: A government perspective. AB - The use of irradation to improve the safety, protect the nutritional benefits, and preserve the quality of fresh and processed foods is a well established and proven technology. Over the past 30 years, the United States Government has invested in the science to confirm safety and in the technology to show application. The United States Department of Agriculture and the Food and Drug Administration have approved sources of ionizing radiation for the treatment of foods, and their application to most meats, fruits, vegetables, and spices. Despite the value of this technology to the food industry and to the health and welfare of the public, only minimal application of this technology occurs. This underscorces the importance of increasing the public's understanding of radiation risks relative to other hazards. Accordingly, the Committee on Interagency Radiation Research and Policy Coordination of the Executive Office of the President has made recommendations for the creation of a centralized National Radiation Information Center that would work closely with Federal departments and agencies in responding to public queries about radiation issues and Federal programs. PMID- 24234955 TI - Fate and exposure models in relation to risk assessment : Developments and validation criteria. AB - The recognition of potential long-term effects of substances, has led to the development of regulations and legislation which emphasis the need for assessing the risks posed by both new and existing substances for man and the environment. The evaluation of fate and exposure models is put into perspective in relation to the developments over the last five years in the framework of the EU regulations and national legislation within the European Community. The validation of environmental exposure models (multi-media models) is described in the context of quality assurance of models available to a user group, which is different from the quality assurance aspects for a developers group. PMID- 24234956 TI - Preface : From mechanistic studies to applications in risk assessment. PMID- 24234958 TI - Ozone-depleting substances and artificial greenhouse gases : Amendments to the ordinance on environmentally hazardous substances in Switzerland. PMID- 24234957 TI - Greenhouse gas induced climate change. AB - Simulations using global coupled climate models predict a climate change due to the increasing concentration of greenhouse gases and aerosols in the atmosphere. Both are associated with the burning of fossil fuels. There has been considerable debate if this postulated human influence is already evident. This paper gives an overview on some recent material on this question. One particular study using optimal fingerprints (Hegerl et al., 1996) is explained in more detail. In this study, an optimal fingerprint analysis is applied to temperature trend patterns over several decades. The results show the probability being less than 5% that the most recently observed 30 year trend is due to naturally occurring climate fluctuations. This result suggests that the present warming is caused by some external influence on climate, e.g. by the increasing concentrations of greenhouse gases and aerosols. More work is needed to address the uncertainties in the magnitude of naturally occurring climate fluctuations. Also, other external influences on climate need to be investigated to uniquely attribute the present climate change to the human influence. PMID- 24234959 TI - The international register of potentially toxic chemicals : Challenges of data collection in the field of toxicology. AB - The benefits and drawbacks consequent to the widespread use of chemicals are inextricably interwoven. According to recent estimates, more than 8 million substances are presently known, 70,000 of which are in common use as industrial compounds, pesticides, Pharmaceuticals, food additives, cosmetics and the like. It is estimated that substances used as such will increase annually by 1000 in number. The deleterious consequences deriving from their exploitation pose tremendous challenges to the scientific community for the protection of human health and the environment. Therefore it is of utmost priority to appropriately select valid information generated in this investigation area and to convey it correctly to users. Here, the adoption of the principles of good laboratory practice in experimental activities is essential, as well as the creation of global networks for data exchange on the safe use of chemicals. The structure and goals of the International Register of Potentially Toxic Chemicals (IRPTC, the database of the United Nations Environment Programme) are detailed to give an example of such an undertaking. Seventeen fields are covered,i.e. identifiers, properties and classification, production/trade, production processes, use, pathways into the environment, concentrations, environmental fate tests, environmental fate, chemobiokinetics, mammalian toxicity, special toxicity studies, effects on organisms in the environment, sampling/preparation/analysis, spills, treatment of poisoning, waste management and recommendations/legal mechanisms. PMID- 24234960 TI - Understanding regional metabolism for a sustainable development of urban systems. AB - Cities are the most complex forms of settlements which man has built in the course of his cultural development. Their "metabolism" is connected with the world economy and is run mainly by fossil energy carriers. Up to now there are no validated models for the evaluation of a sustainable development of urban regions.The guidelines for a "sustainable development" suggest the reduction of resource consumption. The article is concerned with the problem of how the "sustainable-development concept" can be transformed from a global to a regional scale. In urban settlements the strategy of final storage should be applied. By this, the subsystem waste management can be transformed within 10 to 15 years to a "sustainable status".With regard to the system "agronomy", the article concludes that agriculture in urban systems should focus on food production instead of promoting reduction of food production in favour of energy plants, which is not a suitable strategy.The main problems are the energy carriers. Transformation to a "sustainble status" is only possible by a reconstruction of the urban system, i.e. of buildings and the transportation network. The rate determining step in achieving such a status is the change in the fabric of buildings and in the type of transportation networks. The reconstruction of an urban system needs, mainly for economical reasons, a time period of two generations. PMID- 24234961 TI - IMTOX - An interdisciplinary initiative. PMID- 24234963 TI - 11th Applied Geologic Remote Sensing Conference and Workshops : Practical solutions for real world problems Las Vegas, USA, 27-29 February 1996. PMID- 24234962 TI - Sources of airborne CC14 : Critical remarks. AB - Atmospheric mixing ratios of chlorinated C1 and C2 hydrocarbons (CHCs) were measured at the mountain Wank (Garmisch-Partenkirchen, Bavarian Alps) in autumn 1992. The data lead to the assumption that at least part of the observed CC14 originates from a source different to the other CHCs measured (C2HCL3, C2C14, CHCl3 and CH3CCl3). The nature of this source is discussed. PMID- 24234965 TI - Parathyroid Carcinoma in the Setting of Tertiary Hyperparathyroidism after Renal Transplant. PMID- 24234966 TI - A new approach to casino licensing problems in the United Kingdom. AB - The British Gaming Act 1968 is generally considered to be one of the strongest pieces of legislation that regulates and oversees a casino industry within its jurisdiction. The casino gaming industry in Great Britain is held to a very high standard, with potential for significant penalties if either the spirit or the letter of the law is violated. Such penalties have been invoked more than once in the past. The recent case involving London Clubs, the largest casino company operating in London, led to events that may have changed the underlying relationship of the review process among the Gaming Board, the Police, and the Courts. This article examines the details of that case, and the implications for the British casino industry and regulatory structure. PMID- 24234967 TI - Norwegian lottery winners: Cautious realists. AB - The study investigated 261 lottery winners of prizes of NKR 1 million (US $150,000) or more in the years 1987-91 in a postal survey. The modal Norwegian winners were middle-aged married men of modest education, living in small communities. Emotional reactions to winning were few, aside from moderate happiness and relief. Winners emphasized caution, emotional control and unconspicuous spending, e.g. paying debts and sharing with children. There was only a slight increase in economic spending. A wish for anonymity was frequent, together with fear of envy from others. Betting was modest both before and after winning. Experiences with winning were predominantly positive. Life quality was stable or had improved. An age trend was observed, accounting for more variance than any other variable. The older winners seemed to represent a puritan subculture of caution, modesty and emotional restraint. A slightly more impatient pattern of spending was characteristic of younger winners. The results support Kaplan's 1987 and others' findings that lottery winners are not gamblers, but self-controlled realists and that tenacious, negative cultural expectations to the contrary are myths, but perhaps also deterrents of uncontrolled behavior. PMID- 24234968 TI - Market behavior of gaming stocks: An analysis of the first twenty years. AB - Gaming stocks have now been publicly traded on the stock exchange for about twenty years. This study looks at the price movement patterns of gaming stocks compared with the broader market for six stock market cycles between 1973 and 1992. The study suggests that gaming stocks tend to be more volatile than the market as a whole and that this has been true throughout the twenty year period. It also shows that gaming stocks have risen in price during this period at a rate much greater than that for the general market. Special events, such as the establishment of gaming in New Jersey, can cause the gaming stocks to move in a direction opposite to the general market. Finally, the findings indicate that gaming stocks are especially susceptible to stock market declines which are related to concerns about the price or availability of oil. PMID- 24234969 TI - Pathological gambling among adolescents: Massachusetts Gambling Screen (MAGS). AB - This article describes the development of the Massachusetts Gambling Screen (MAGS). The purpose of the MAGS is to provide a brief clinical screening instrument that can (1) yield an index of non-pathological and pathological gambling during a 5 to 10 minute survey or interview and (2) document the first psychometric translation of the proposed DSM-IV pathological gambling criteria into a set of survey or clinical interview questions. The development data for this instrument were obtained from a survey of 856 adolescents who were students in suburban Boston high schools. The results provided evidence that weighted item scores (i.e., discriminant function coefficients) could correctly classify 96% of adolescent gamblers as pathological, in transition or non-pathological when DSM IV criteria were employed as the conceptual referent. The results also describe the prevalence of a variety of social and emotional problems associated with adolescent gambling. Finally, the discussion examined the normalization and contemporary social context of gaming and the impact of these influences on the measurement and identification of pathological gambling. PMID- 24234970 TI - Gambling among primary school students. AB - This study identifies the gambling behavior of 1,320 primary school students aged 8 to 12 of the 4th, 5th and 6th grades. Eighty-six percent admitted to having, at some time or another, bet money. Lotteries are the most popular form of gambling for this age group. Sixty-one percent of these students gamble with lotteries. In descending order of popularity, other games played by students were: bingo, card playing for money, bets on sports, wagering on specific events, video gambling (video poker and slot machines), and finally betting on games of skill. Gambling behaviors differed according to gender. More than 40% of respondents reported gambling once a week or more for at least one game. Because of the early development of gambling behavior in children, prevention programs for pathological gambling should be implemented as early as the fourth grade. PMID- 24234971 TI - An exploratory study of gambling cross addictions. AB - A growing body of empirical and theoretical research has concentrated on the overlaps and commonalities among chemical and non-chemical (behavioural) addictions. Pathological gambling has perhaps been the most widely researched behavioural addiction and some of this research has concerned the co-existing links between pathological gambling and alcohol/drug addiction in both the gambling substance abuser and the substance abusing gambler (i.e. cross addiction). This study was of an exploratory nature and attempted to gather information and data regarding gambling cross addictions in the UK. To achieve this, 456 letters were sent to all drug and alcohol helping agencies in England requesting such information. This yielded 210 returns (46% response rate). Results indicated that gambling cross addictions occur in both adults and adolescents and were almost exclusively a male condition. However, it must be noted only just over half of the responding agencies had encountered gambling cross addiction and reasons for this are speculated. Results also indicated the existence of various cross addicted subgroups including an adolescent subgroup who were addicted to fruit machines and abused solvents. Future research ideas are also discussed. PMID- 24234972 TI - Epidemiological surveys of pathological gambling: Critique and suggestions for modification. AB - Epidemiological studies of problem and pathological gambling were examined for their accuracy. Fundamental flaws and biases were found in these surveys. These include problems with survey instruments; nonresponses and refusal bias; the exclusion of institutionalized populations; exclusion of other groups; and failure to protect against denial on the part of the respondent when others are present near the telephone. Based on the issues discussed, one can reasonably be expected to assume that most epidemiological surveys seriously underestimate the extent of problem and pathological gambling. Alternative strategies for addressing these issues are discussed. These strategies include the use of field interviews, surveys of institutionalized populations, frequent player surveys and significant other surveys. The value and potential problems of these approaches are also discussed. PMID- 24234973 TI - Social cost of pathological gambling. AB - Pathological gambling creates enormous problems for the afflicted individuals, their families, employers, and society, and has numerous disastrous financial consequences. The present study evaluates the financial burdens of pathological gambling by questioning pathological gamblers in treatment in Gamblers Anonymous (n=60; 56 males, 4 females; mean age = 40 years old) about personal debts, loss of productivity at work, illegal activities, medical costs and the presence of other dependencies. Results show that important debts, loss of productivity at work and legal problems are associated with pathological gambling. Discussion is formulated in terms of the social cost of adopting a liberal attitude toward the legalization of various gambling activities. PMID- 24234974 TI - Gated SPECT in assessment of regional and global left ventricular function: an update. AB - Gated myocardial perfusion SPECT (GSPECT) is a major clinical tool, widely used for performing myocardial perfusion imaging procedures. In this review, we have presented the fundamentals of GSPECT and the ways in which the functional measurements it provides have contributed to the emergence of myocardial perfusion SPECT in its important role as a major tool of modern cardiac imaging. GSPECT imaging has shown unique capability to provide accurate, reproducible and operator-independent quantitative data regarding myocardial perfusion, global and regional systolic and diastolic function, stress-induced regional wall-motion abnormalities, ancillary markers of severe and extensive disease, left ventricular geometry and mass, as well as the presence and extent of myocardial scar and viability. Adding functional data to perfusion provides an effective means of increasing both diagnostic accuracy and reader's confidence in the interpretation of the results of perfusion scans. Assessment of global and regional LV function has improved the prognostic power of myocardial perfusion SPECT and has been shown in a large registry to add to the perfusion assessment in predicting benefit from revascularization. PMID- 24234976 TI - The effect of head position on scapular orientation and muscle activity during shoulder elevation. AB - The purposes of this study were to compare the effects of flexed head positions on scapular orientation and muscle activity during humeral elevation, and to determine any association of kinematic and electromyographic (EMG) responses. Twenty-five subjects, 19-37 years old and without any recent history of shoulder or neck symptoms, were evaluated. Three-dimensional scapular coordinate data and surface EMG signals from the trapezius (upper and lower), levator scapulae, and serratus anterior were collected at static positions (0 degrees , 90 degrees , and 140 degrees ) of humeral elevation in the scapular plane and head positions (0 degrees , 25 degrees , and 50 degrees ) of sagittal plane flexion. Scapular upward rotation and tipping were significantly decreased in flexed head positions. The effect of head position on scapular tipping increased as humeral elevation increased. Mean EMG activity of the levator scapula, upper trapezius, and serratus anterior was unchanged across head positions. The lower trapezius demonstrated small but statistically significant increases in mean activity at the 0 degrees and 140 degrees arm positions when the head was flexed to 50 degrees . Significant correlations were found between some EMG and kinematic responses in flexed head positions, however, no consistent patterns were apparent across muscles or positions. PMID- 24234978 TI - Exercise for workers with musculoskeletal pain: Does enhancing compliance decrease pain? AB - A low rate of compliance for exercise regimens is a difficult problem for programs aimed at treating or preventing musculoskeletal pain. In fact, the utility of exercise for common pain problems has been debated since poor compliance confounds proper program evaluation. Thus, the purpose of the present study was to evaluate the effects of a compliance enhancement measure and subsequently to assess the effects of physical activity on pain perception. Forty eight employees (mean age=42, 20 females) currently working at two companies and who reported musculoskeletal pain, but noexercise habit voluntarily served as subjects. The Comparison Group was provided with information and free membership at a health center. The Exercise Compliance Enhancement Group met individually with a behavioral psychologist, who employed cognitive-behavioral techniques, to plan their activity program. Results showed that the Compliance Enhancement Group had a higher rate of adherence and participated in significantly more exercises over the course of 6 months than did the Comparison Group. However, analyses based on pre- and posttest gain scores showed that the differences between the groups for aerobic capacity and pain intensity were not significant. However, when compilers were compared with noncompliers, those complying with the activity program were found to have improved their aerobic capacity more than noncompliers. Yet for overall pain intensity ratings, the difference between compilers and noncompliers was still not significant. Intensity ratings made immediately before and after exercising indicated that exercise activities were related to a significant increase in pain intensity. These results indicate that compliance for exercise may be significantly improved, but the effect of exercise activities on overall pain intensity was not significant relative to the comparison group. PMID- 24234977 TI - The reliability and validity of a measure of perceived functional capacity for work in chronic back pain. AB - Psychosocial factors, including perceived disability and self-efficacy, are important determinants of outcome for individuals with chronic back pain. Consequently, there is a need for an evaluation and consideration of such factors in occupational rehabilitation. This study evaluated the reliability and validity of a tool, the Spinal Function Sort, as a measure of perceived capacity for work related tasks with 42 rehabilitation clients with chronic back pain. Results provided support for the internal consistency (Cronbach's alpha of 0.97), test rest reliability (ICC of 0.89) and construct validity of the Spinal Function Sort as a measure of perceived capacity for work-related tasks in persons with chronic back pain. Measures of similar constructs were significantly correlated with the Spinal Function Sort and were highly predictive of the Spinal Function Sort on multiple regression. Relationships between perceived work capacity and pain intensity and gender are discussed. The need for the consideration of perceived capacity in the evaluation and rehabilitation of persons with chronic back pain is highlighted. PMID- 24234979 TI - Effects of occupationally-oriented rehabilitation on farmers' work techniques, musculoskeletal symptoms, and work ability. AB - Changes in work techniques, musculoskeletal symptoms and work ability were studied after occupationally-oriented rehabilitation courses for farmers experiencing low back or shoulder pain. Fifty-two women and 43 men participated. The OWAS analysis of work postures, biomechanical modeling of lifting techniques, and a questionnaire were used before and after the courses and after 1 year of follow-up. Bent and twisted postures or postures with the arms over the shoulders occurred more seldom after the courses and the follow-up. Changes in lifting techniques were minor. The musculoskeletal pain index decreased by 12 and 3 points for the women and men, respectively. The mean work ability index increased from 33.5 (men and women) to 36.5 (women) and 35.1 (men). This study showed that rehabilitation can produce significant, long-lasting effects on rehabilitees' work techniques, work ability, and subjective well-being. PMID- 24234980 TI - Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke. AB - BACKGROUND: Stroke is one of the leading causes of disability worldwide. Functional impairment resulting in poor performance in activities of daily living (ADLs) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance and function after stroke, but a possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability and hence to improve ADL performance and function. OBJECTIVES: To assess the effects of tDCS on generic activities of daily living (ADLs) and motor function in people with stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013), MEDLINE (1948 to May 2013), EMBASE (1980 to May 2013), CINAHL (1982 to May 2013), AMED (1985 to May 2013), Science Citation Index (1899 to May 2013) and four additional databases. In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials (from which we analysed only the first period as a parallel-group design) that compared tDCS versus control in adults with stroke for improving ADL performance and function. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. MAIN RESULTS: We included 15 studies involving a total of 455 participants. Analysis of six studies involving 326 participants regarding our primary outcome, ADL, showed no evidence of an effect in favour of tDCS at the end of the intervention phase (mean difference (MD) 5.31 Barthel Index (BI) points; 95% confidence interval (CI) -0.52 to 11.14; inverse variance method with random-effects model), whereas at follow-up (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random-effects model), we found evidence of an effect. However, the confidence intervals were wide and the effect was not sustained when only studies with low risk of bias were included. For our secondary outcome, upper limb function, we analysed eight trials with 358 participants, which showed evidence of an effect in favour of tDCS at the end of the intervention phase (MD 3.45 Upper Extremity Fugl-Meyer Score points (UE-FM points); 95% CI 1.24 to 5.67; inverse variance method with random-effects model) but not at the end of follow-up three months after the intervention (MD 9.23 UE FM points; 95% CI -13.47 to 31.94; inverse variance method with random-effects model). These results were sensitive to inclusion of studies at high risk of bias. Adverse events were reported and the proportions of dropouts and adverse events were comparable between groups (risk difference (RD) 0.00; 95% CI -0.02 to 0.03; Mantel-Haenszel method with random-effects model). AUTHORS' CONCLUSIONS: At the moment, evidence of very low to low quality is available on the effectiveness of tDCS (anodal/cathodal/dual) versus control (sham/any other intervention) for improving ADL performance and function after stroke. Future research should investigate the effects of tDCS on lower limb function and should address methodological issues by routinely reporting data on adverse events and dropouts and allocation concealment, and by performing intention-to-treat analyses. PMID- 24234981 TI - Psychoanalysis as poetry. AB - Like psychoanalysis, poetry is possible because of the nature of verbal language, particularly its potentials to evoke the sensations of lived experience. These potentials are vestiges of the personal relational context in which language is learned, without which there would be no poetry and no psychoanalysis. Such a view of language infuses psychoanalytic writings on poetry, yet has not been fully elaborated. To further that elaboration, a poem by Billy Collins is presented to illustrate the sensorial and imagistic potentials of words, after which the interpersonal processes of language development are explored in an attempt to elucidate the original nature of words as imbued with personal meaning, embodied resonance, and emotion. This view of language and the verbal form allows a fuller understanding of the therapeutic processes of speech and conversation at the heart of psychoanalysis, including the relational potentials of speech between present individuals, which are beyond the reach of poetry. In one sense, the work of the analyst is to create language that mobilizes the experiential, memorial, and relational potentials of words, and in so doing to make a poet out of the patient so that she too can create such language. PMID- 24234982 TI - Analysis begins in the analyst's mind: conceptual and technical considerations on recommending analysis. AB - For certain patients who approach analysts for treatment, analysis remains the only treatment that can provide the urgent and at times lifesaving help they need. At the same time, recommending analysis presents analysts with a surprisingly challenging emotional task. Because patients will not be able to get analytic help unless the analyst recommends it and facilitates the patient's engagement, it is vital that analysts identify the conditions that make the beginning of analysis possible. Analysis, it is argued, begins in the analyst's mind: how analysts think about their function, their patients, and the analytic process determines in great measure whether analysis will begin. Six essential components of the analyst's mindset are presented, as well as technical considerations about recommending analysis that are based on this mindset and that have been useful in initiating analysis. A detailed clinical example is provided to illustrate how the analyst's thinking informed the initial phase of a treatment with a patient who engaged in a productive analysis. PMID- 24234983 TI - Remembering lauretta bender. PMID- 24234984 TI - Highlights in pioneering the understanding of language disabilities. PMID- 24234986 TI - The Orton trail: 1896-1986. PMID- 24234985 TI - The theory of multiple intelligences. PMID- 24234987 TI - Application of disconnection concepts to developmental dyslexia. PMID- 24234988 TI - Is phonology bypassed in normal or dyslexic development? AB - A pervasive assumption in most accounts of normal reading and spelling development is that phonological coding is important early in development but is subsequently superseded by faster, orthographic coding which bypasses phonology. We call this assumption, which derives from dual process theory, the developmental bypass hypothesis. The present study tests four specific predictions of the developmental bypass hypothesis by comparing dyslexics and nondyslexics from the same families in a cross-sectional design. The four predictions are: 1) That phonological coding skill develops early in normal readers and soon reaches asymptote, whereas orthographic coding skill has a protracted course of development; 2) that the correlation of adult reading or spelling performance with phonological coding skill is considerably less than the correlation with orthographic coding skill; 3) that dyslexics who are mainly deficient in phonological coding skill should be able to bypass this deficit and eventually close the gap in reading and spelling performance; and 4) that the greatest differences between dyslexics and developmental controls on measures of phonological coding skill should be observed early rather than late in development.None of the four predictions of the developmental bypass hypothesis were upheld. Phonological coding skill continued to develop in nondyslexics until adulthood. It accounted for a substantial (32-53 percent) portion of the variance in reading and spelling performance in adult nondyslexics, whereas orthographic coding skill did not account for a statistically reliable portion of this variance. The dyslexics differed little across age in phonological coding skill, but made linear progress in orthographic coding skill, surpassing spelling-age (SA) controls by adulthood. Nonetheless, they didnot close the gap in reading and spelling performance. Finally, dyslexics were significantly worse than SA (and Reading Age [RA]) controls in phonological coding skill only in adulthood. PMID- 24234989 TI - The use of morphological knowledge in spelling derived forms by learning-disabled and normal students. AB - Currently popular systems for classification of spelling words or errors emphasize the learning of phoneme-grapheme correspondences and memorization of irregular words, but do not take into account the morphophonemic nature of the English language. This study is based on the premise that knowledge of the morphological rules of derivational morphology is acquired developmentally and is related to the spelling abilities of both normal and learning-disabled (LD) students. It addresses three issues: 1) how the learning of derivational morphology and the spelling of derived words by LD students compares to that of normal students; 2) whether LD students learn derived forms rulefully; and 3) the extent to which LD and normal students use knowledge of relationships between base and derived forms to spell derived words (e.g. "magic" and "magician"). The results showed that LD ninth graders' knowledge of derivational morphology was equivalent to that of normal sixth graders, following similar patterns of mastery of orthographic and phonological rules, but that their spelling of derived forms was equivalent to that of the fourth graders. Thus, they know more about derivational morphology than they use in spelling. In addition, they were significantly more apt to spell derived words as whole words, without regard for morphemic structure, than even the fourth graders. Nonetheless, most of the LD spelling errors were phonetically acceptable, suggesting that their misspellings cannot be attributed primarily to poor knowledge of phoneme-grapheme correspondences. PMID- 24234990 TI - Developmental dyslexia: Is it different from other forms of reading disability? AB - A controversy whether developmental dyslexia is qualitatively different from other forms of reading disability has existed among reading specialists for many years. In the present study, the hypothesis that the etiology of dyslexia is different from that of other forms of reading disability because of differences in the components that malfunction was tested. A number of studies have shown that the two components that contribute to a large proportion of variance in reading are decoding and comprehension. It is, therefore, possible that a breakdown of different components could lead to different forms of disabilities. College students who were poor readers were assigned to two groups on the basis of their IQ. Conforming to the traditional criterion of dyslexia, those who had an IQ of 95 and above were considered as dyslexic. Those who had an IQ of 85 or below were placed in the Nonspecific Reading-Disabled group. These two groups of poor readers and a group of normal readers were administered a large number of reading-related tests. It was found that the two reading-disabled groups differed from each other in six of the seven areas assessed. There was very little overlap of scores between the two groups in these areas. The results were interpreted to suggest that poor decoding skill is the etiology of developmental dyslexia and that it differs from other forms of reading disability which are caused by generalized cognitive deficits. PMID- 24234991 TI - Segmental analysis of speech and its relation to reading ability. AB - The relationships between the acquisition of segmental awareness, i.e. the awareness of phonemic and phonetic units, and the acquisition of alphabetic literacy are examined: segmental awareness is elicited by learning to read and write in the alphabetic system and is crucial to success in this learning. It is also argued that the development of the ability of explicit analysis of speech into segments requires ageneral analytic capacity.Cognitive explanations of dyslexia must take into account the fact that the ability of segemental analysis of most dyslexics is very poor. Given that dyslexics do not lack experience with alphabetic material nor, as suggested by their performance on nonspeech tasks, analytic capacity, one likely factor of this inability may be related to the conscious representation of speech on which the analytic capacity operates. The normal format of this representation probably corresponds to a sequence of articulatory acts or syllables. In most dyslexics, the format of this representation might not be adequate for the isolation of segments. PMID- 24234992 TI - Gender differences in cognitive abilities of learning-disabled females and males. AB - Gender differences in level and pattern of cognitive abilities were examined in 28 LD college-able females (CA 18-25) as compared to 21 LD college-able males (CA 18-25). Both groups were in the average IQ range as measured by the Wechsler Adult Intelligence Scale, with LD males significantly higher on the Full Scale IQ and three out of the four subtests, Picture Completion, Block Design, and Information. The LD females performed significantly better on the Digit Symbol subtest. The hierarchies of subtest performance and Bannatyne and ACID category scores were compared. LD females have strengths in visual-motor abilities and verbal conceptualization, while the LD males' highest abilities were nonverbal visual-spatial confirming earlier studies on younger LD individuals and non-LD males and females. Performance on the Digit Symbol subtest was the next to the lowest for the males, the highest for females. However, for both groups, short term and long-term memory for digits and factual knowledge and mental arithmetic problem solving were relative weaknesses. Results indicate different patterns of cognitive abilities in LD females and males which have implications for identification, service, and prognosis for the learning disabled, especially females. PMID- 24234993 TI - Reading disability subtypes in neurologically-impaired students. AB - Three studies were conducted in order to determine if reading disability subtypes identified by Mattis, Boder, and Doehring were present in neurologically-impaired students with and without reading disabilities. The anomic-language disorder subtype, dysphonetic and mixed dysphonetic-dyseidetic subtypes, and Doehring's three subtypes were all present, primarily in the reading-disabled sample. Subtypes related to visual-spatial impairment were equally or more apparent in the non-reading-disabled sample. It is concluded that the visual-perceptual disorder subtypes may reflect neurological impairment but be unrelated to reading disability. It remains tenable to hypothesize that the other subtypes found may reflect the ways in which neurological impairment interferes with reading and that subtle neurological impairment may be present in dyslexic students who fall into the same subtypes. PMID- 24234994 TI - Multisensory teaching approach for reading, spelling, and handwriting, Orton Gillingham based curriculum, in a public school setting. AB - This paper includes an overview of curriculum information and the basic techniques of a multisensory approach for teaching alphabet and dictionary skills, reading, spelling, and cursive handwriting. It also reports the results of a four-year study of reading and spelling in both remedial and nonremedial classes in a public school. The California Achievement Test (CAT) scores in reading and spelling for students in both remedial and nonremedial classes improved over baseline scores following this multisensory approach. Additionally, there was a tendency for the CAT mean scores to increase corresponding to the number of years students had been taught by the multisensory program. PMID- 24234995 TI - Dyslexia: Especially for parents. PMID- 24234996 TI - Scholastic Aptitude Test preparation for the adolescent dyslexic. AB - Residual signs characteristic of a specific language disability, such as vocabulary deficits, trouble differentiating between literal and figurative words, difficulty paraphrasing a reading selection, and problems with abstract reasoning make it arduous for dyslexic adolescents to demonstrate their maximum potential on the verbal section of the Scholastic Aptitude Test. This paper illustrates ways in which SAT skills can be enhanced through a structured program of vocabulary development, an understanding of test taking strategies for specific SAT questions, and the learning of a pattern of analysis to improve reading comprehension. It includes case studies, as well as a discussion of the types of special test arrangements available for dyslexic students. PMID- 24234997 TI - Handwriting: Evolution and evaluation. AB - Handwriting, "everyone's art," is an indispensable skill. The roots of our present forms of penmanship are traced. When and which initial style to teach children, especially the dyslexic or learning disabled, are discussed.The need for a good instrument to evaluate handwriting to prevent perpetuation of illegibilities or to determine if speed is rapid enough to meet the writer's purpose is paramount. A new diagnostic tool, the Children's Handwriting Evaluation Scale (CHES) and its college counterpart are detailed. The CHES also provides a projective scoring key based on graphoanalytic interpretations. PMID- 24234998 TI - Reading development in adults. AB - A comparison of the development of reading ability among adults with that of children-from the lowest levels of literacy to the most advanced. Included in the comparison are characteristics of adults at each level of development, the kind of instruction that will help bring them from lower to higher levels, and the particular difficulties they experience at the various levels. The article concludes with a historical overview of the changes in literacy standards and needs in the United States and the growing recognition that among the adult illiterates, particularly native English speakers who have very limited reading skills, are large numbers who have dyslexia. PMID- 24234999 TI - The adult outcomes of children with learning disabilities. AB - The results of four follow-up studies of learning-disabled children are reviewed. A comparison of results among the studies and of analyses of individual variation within the studies suggest some factors associated with long-term outcomes. It is argued that in many cases learning disabilities are not a lifelong handicapping condition, especially if adequate treatment is provided during childhood. PMID- 24235000 TI - A new look at comprehension instruction for disabled readers. AB - The traditional specific skills approach to comprehension instruction is no longer considered useful since research has demonstrated that comprehension is a holistic process. However, one must break down the process in some way in order to teach it. Three models of comprehension instruction that attempt to break down the process are described. Strengths and weaknesses of each of the three models: text-based instruction, explicit comprehension instruction, and a combined model, are discussed. Techniques which are exemplars of each of the models are described in relation to their use with reading-disabled children. The combined model of comprehension instruction is recommended because it joins the goal of understanding the text with helping children learn how to learn. PMID- 24235001 TI - Foreword. PMID- 24235002 TI - Excitation modes for fourier transform-ion cyclotron resonance mass spectrometry. AB - Various geometric configurations for the excitation of coherent ion motion in Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR/MS) are analyzed (in some cases for the first time) with unified notation. The instantaneous power absorption, F v, in which v is ion velocity and F the force produced by the applied excitation electric field (harmonic, single frequency, on resonance, in-phase), is time averaged and then set equal to the time rate of change of ion total (cyclotron + magnetron + trapping) energy, to yield a differential equation that is readily solved for the (time-dependent) amplitude of each of the various ion motions. The standard FT-ICR excitation (namely, radial dipolar) is reviewed. The effects of quadrature and radial quadrupolar excitation on ion radial (cyclotron and magnetron) motions are also reviewed. Frictional damping is shown to decrease the ion cyclotron orbital radius and trapping amplitude but increase the magnetron radius. Feedback excitation (i.e., excitation at the simultaneously detected ion cyclotron orbital frequency of the same ion packet) is introduced and analyzed as a means for exciting ions whose cyclotron frequency changes during excitation (as for relativistically shifted low-mass ions). In contrast to conventional radial dipolar excitation, axial dipolar excitation of the trapping motion leads to a mass-dependent ion motional amplitude. Parametric (i.e., axial quadrupolar) excitation is shown to produce an exponential increase in the ion motional amplitudes (hyperbolic sine and hyperbolic cosine amplitude for cyclotron and magnetron radii, respectively). More detailed consideration of parametric excitation leads to an optimal ion initial radial position in parametric-mode FT-ICRjMS. PMID- 24235003 TI - Silver nitrate chemical ionization for analysis of hydrocarbon polymers by laser desorption fourier transform mass spectrometry. AB - Addition of silver nitrate to nonpolar hydrocarbon polymer solutions prior to their analysis by laser desorption Fourier transform mass spectrometry is shown to allow efficient silver ion chemical ionization. High-quality mass spectra are thus obtained for polymers, such as polystyrene, polyisoprene, polybutadiene, and polyethylene, that previously failed to yield useful mass spectra using conventional laser desorption. Accurate mass measurement experiments and isotopic ratios verify that the spectra are those of silver-attached oligomer ion distributions. Mass measurement errors for complete oligomer distributions average between 3 and 12 ppm for oligomers with masses between 400 and 6000 D whereas unit mass resolution is maintained throughout the entire spectral range. PMID- 24235004 TI - Decompositions of cationized heterodimers of amino acids in relation to charge location in peptide ions. AB - The unimolecular decompositions of protonated heterodimers of native and derivatized amino acids to yield the protonated monomers were studied as a guide to charge location in peptide ions. Analyses using a hybrid instrument of BEqQ geometry demonstrated the advantages (with respect to mass resolution, sensitivityr reproducibility, and the elimination of extraneous signals) of the detection of product ions formed in the radiofrequency-only quadrupole region (q) rather than in the field-free region between Band E. Conversion of arginine to dimethylpyrimidylomithine (DMPO) reduced the proton affinity, as evidenced by the decomposition of the protonated arginine/DMPO heterodimer. Conversion of cysteine to pyridylethylcysteine enhanced the proton affinity. Application of these derivatization procedures to peptides resulted in changes in the observed fragmentations of the protonated precursors consistent with the predicted modifications in charge location. Unimolecular decomposition of the protonated dimer composed of glycine and N-acetylglycine yielded both protonated monomers with abundances differing by a factor of only 2; this suggests that in protonated peptides, the amide bonds are competitive with the N-terminal amino group as sites of protonation. It is clear that the propensities to proton' or metal cation location at particular sites in peptides are influenced by both short- and long-range intraionic interactions. In peptides composed of amino acids of similar cation affinities, it may be postulated that the ion population is heterogeneous with respect to the site of charge, with consequent promotion of multiple low-energy fragmentation routes. PMID- 24235005 TI - Determination of high-energy fragmentation of protonated peptides using a beqq hybrid mass spectrometer. AB - A hybrid tandem instrument of BEqQ geometry was used to determine high-energy decomposition of protonated peptides, such as side-chain fragmentation yielding d n and w n ions. The transmission through both E and Q of such product ions, formed in the second field-free region, permits improved mass resolution and confident mass assignment. The experimental technique may involve synchronous scanning of E and Q, or, for the purpose of identification of specific products, limited-range scanning of either E or Q with the other analyzer fixed. These techniques are not equivalent, with respect to product ion transmission, to the double focusing of product ions achieved with four-sector instruments but nevertheless represent a critical improvement over conventional mass-analyzed ion kinetic energy spectrometry analyses. Fragmentation of protonated peptides occurring in the second field-free region inside and outside the collision cell were distinguished by floating the collision cell above ground potential. Mass filtering using Q confirmed the mass assignments. The data indicate that product ions resulting from spontaneous decomposition are in some instances quantitatively more significant than those resulting from high-energy collisional activation. Furthermore, the differentiation of the products of low- and high energy processes should facilitate spectral interpretation. PMID- 24235006 TI - Dehydration of peptide [M + H](+) ions in the gas phase. AB - The loss of water from protonated peptides was studied using [(18)O]-labeling of the C-terminal carboxyl group. The structures (including the location of the isotopic label) of first-generation product ions were examined by sequential product ion scanning (MS(3) and MS(4)) using a hybrid sector/quadrupole mass spectrometer. Water loss may involve carboxylic acid groups, side-chain hydroxyls, or peptide backbone oxygens. Although one of these three pathways often predominates, more than one dehydration route can be operative for a single peptide structure. When peptide backbone oxygen is lost, the dehydration can occur at one or two primary sites along the backbone, with the location of the site(s) varying among peptides. When water loss involves the C-terminal carboxyl group, the resulting ion may undergo extensive intraionic oxygen isotope exchange. This evidence for complex intraionic interactions further emphasizes the significance of gas-phase conformation in determining the fragmentations of peptide ions. PMID- 24235008 TI - Fast-atom bombardment of the cyclic acetals: Evidence indicating the predominant involvement of condensed-phase processes in ionization. AB - A series of cyclic acetals, the 2-phenyl-l,3 dioxolanes, and their deuterated analogues were studied by electron ionization (EI), chemical ionization (CI), and fast-atom bombardment (FAB) mass spectrometry to gain insight into the primary ionization processes for these compounds in FAB/liquid secondary ion mass spectrometry. Comparison of EI and CI data with that of FAB led to the conclusion that the predominant [M - H]+ ion observed in FAB for the nondeuterated cyclic acetals cannot to a large extent be rationalized in thermodynamic terms by known gas-phase ion-molecule reactions. Instead, a condensed-phase model in which the multicharged transition state for hydride abstraction is better solvated than the transition state for proton transfer appears to be a plausible explanation for the FAB data obtained for the nonlabeled cyclic acetals; however, this explanation is not entirely sufficient to rationalize the FAB data for the deuterated cyclic acetals. For these compounds, a dramatic time dependence of protonation versus hydride abstraction is observed that suggests that beam induced reactive species are responsible for hydride abstraction in the condensed phase. This time dependence can be interpreted in terms of a buildup of highly reactive beam-induced species in the bulk of solution. Comparison of the results obtained for deuterated acetals with different surface activities support this hypothesis. (J Am Sot Mass. PMID- 24235007 TI - Evaluation of the true effect of experimental parameters on the reduction / oxidation processes observed in fast-atom bombardment/liquid secondary spectrometry. AB - The peak intensities observed in the molecular ion regions of fast-atom bombardment/liquid secondary ion mass spectra contain contributions from the parent ion species, its one- and two-electron reduction/oxidation products, and chemical background signal due to beaminduced damage. There are several solution and instrumental parameters that can affect the distribution of peak intensities in the molecular ion region. In this study, the analyte concentration and primary beam density and energy were varied systematically to investigate their effects on the measured peak intensities. A computer algorithm, Simbroc (Simulated Background and Reduction/Oxidation Calculations), was designed to deconvolute the observed intensities into their individual components so that the true effects of experimental parameters on redox extent and background levels could be evaluated. The algorithm is based on a comprehensive seven-variable mathematical model for experimental data simulation. The results obtained using the algorithm after its validation indicate that the primary beam energy does not significantly affect redox extent or background levels. Changes in analyte concentration and primary beam density tend to play a more important role in the generation of redox products and beam-induced damage. The background level generally increases as the analyte concentration is lowered for the peptide systems used in this study. An increase in the primary beam density often leads to higher background levels, although the effect is less detectable for samples that have a low (less than 3%) background signal. The apparent two-electron reduction is generally lower at the higher concentrations; however, the "true" reduction occurring for pentaphenylalanine does not show a significant concentration effect. PMID- 24235009 TI - Multisample probe for fast-atom bombardment / mass spectrometry. AB - An inexpensive multisample fast-atom bombardment (FAB) probe assembly was designed for high-throughput analysis of samples on a VG ZAB-SE mass spectrometer. The system consists of a vacuum lock system and a FAB probe whose tip contains five or more sample wells. The probe enters the mass spectrometer source region perpendicular to the secondary ion beam axis, The probe is maintained at high voltage on contact with a spring clip attached to the screen plate of the source block. Sample throughput with the multisample probe is twice that of a coaxial probe, with about twice the sensitivity and no sample cross contamination. PMID- 24235010 TI - On the structure of water-alcohol and ammonia-alcohol protonated clusters. AB - Collision-induced dissociation (CID) of protonated ammonia-alcohol and water alcohol heteroclusters was studied using a triple quadrupole mass spectrometer with a corona discharge atmospheric pressure ionization source. CID results suggested that the ammonia-alcohol clusters had NH: at the core of the cluster and that hydrogen-bonded alcohol molecules solvated this central ion. In contrast, CID results in water-alcohol clusters showed that water loss was strongly favored over alcohol loss and that there was a preference for the charge to reside on an alcohol molecule. The results also indicated that a loose chain of hydrogen-bonded molecules was formed in the water-alcohol clusters and that there appeared to be no rigid protonation site or a fixed central ion. (J Am Soc Mass. PMID- 24235011 TI - Double-ionization energies of fluorinated benzene molecules. AB - Results are reported of an experimental determination by double-charge transfer spectroscopy of the previously unknown double-ionization energies of the fluorinated benzene molecules C6H5F, l,2-C6H4F2, 1,3-C6H4F2, 1,4-C6H4F2, 1,2,3 C6H3F3, 1,2,4-C6H3F3, 1,3,5-C6H3F3, 1,2,3,4-C6H2F4, 1,2,3,5-C6H2F4, 1,2,4,5 C6H2F4, and C6HF5. The data are remarkably similar; the lowest double-ionization energies for all the molecules are within +/-0.5 of 25.7 eV, and the data for higher energies suggest that the distributions of electronic state energies for the dications of the molecules show only small variations. PMID- 24235013 TI - Retinal nerve fiber layer thickness in normal Chinese students aged 6 to 17 years. AB - PURPOSE: We obtained retinal nerve fiber layer (RNFL) thickness measurements in normal Chinese students aged 6 to 17 years, and investigated the relationship between RNFL thickness and sex, eye laterality, age, axial length, and refractive error. METHODS: A total of 4648 eyes in 2324 normal, randomly-selected Chinese students aged 6 to 17 years was examined in this study. The RNFL thickness was measured by optical coherence tomography. The effects of sex, eye laterality (left or right), age, refractive error, and axial length on RNFL thickness were assessed. RESULTS: The average age of the subjects was 12.82 +/- 3.11 years. The global average RNFL thickness (+/-SD) was 106.89 +/- 12.84 MUm. The thickest RNFL measurements were found at the superior (133.22 +/- 19.48 MUm) and inferior (129.23 +/- 20.30 MUm) quadrants of the retina, followed by the temporal (93.58 +/- 29.15 MUm) and nasal (77.10 +/- 14.89 MUm) quadrants. In the 1529 participants aged 12 to 17, there were no significant differences in RNFL thickness values between the right and left eyes (P > 0.05); significant differences in RNFL were found only in the inferior and temporal quadrants of the retina in different sex groups (P < 0.05). Linear regression analysis revealed that the RNFL thickness values were correlated independently with axial length and refractive error (P < 0.05). CONCLUSIONS: For clinical assessment of RNFL thickness, the influence of refractive error and axial length should be taken into account. PMID- 24235014 TI - TNFRSF10A-LOC389641 rs13278062 but not REST-C4orf14-POLR2B-IGFBP7 rs1713985 was found associated with age-related macular degeneration in a Chinese population. AB - PURPOSE: To reassess the association between TNFRSF10-LOC389641 rs13278062 and REST-C4orf14-POLR2B-IGFBP7 rs1713985 with the risk of AMD in a Chinese case control collection. METHODS: The primary study consisted of 1826 subjects, including 1226 controls, 300 cases with nAMD, and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs13278062 and rs1713985 were determined by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. The difference in allele distribution between cases and controls was tested using a chi2 test. We also performed a meta-analysis of case-control studies for rs13278062 and rs1713985 in Hong Kong and Singaporean late AMD collections of Chinese descent (1273 cases and 1652 controls) via an inverse-variance, fixed effects model as previously described. Subgroup analysis of CNV and PCV subtypes were also performed. RESULTS: We found no evidence to support a significant association of markers rs13278062 or rs1713985 with either nAMD or PCV, or total AMD in our Beijing study (P > 0.05 for all comparisons). Upon meta-analysis of all sample collections, we note nominally significant association between rs13278062 and increased risk of late AMD, consistent with previous findings in Japanese individuals (ORmeta = 1.17, Pmeta = 0.004). No association was detected between rs1713985 and AMD when all data were meta analyzed. CONCLUSIONS: SNP rs13278062, but not rs1713985 showed nominal evidence of association with AMD in a total of 1273 cases and 1652 controls of Chinese descent. The difference between different effect sizes in our study and other studies suggested that future studies with much larger sample sizes is necessary. PMID- 24235015 TI - The influence of genetic background on conventional outflow facility in mice. AB - PURPOSE: Intraocular pressure (IOP) varies between genetically distinct strains of mice. The purpose was to test the hypothesis that strain-dependent differences in IOP are attributable to differences in conventional outflow facility (C). METHODS: The IOP was measured by rebound tonometry in conscious or anesthetized BALB/cJ, C57BL/6J, and CBA/J mice (N = 6-10 per strain). Conventional outflow facility was measured by ex vivo perfusion of enucleated eyes (N = 9-10 per strain). RESULTS: Conscious IOP varied between strains, being highest in CBA/J (14.5 +/- 0.9 mm Hg, mean +/- SD), intermediate in C57BL/6J (12.3 +/- 1.0 mm Hg), and lowest in BALB/cJ (10.6 +/- 1.8 mm Hg) mice. Anesthesia reduced IOP and eliminated any detectable differences between strains. Conventional outflow facility also varied between strains, but, in contrast to IOP, C was lowest in CBA/J (0.0113 +/- 0.0031 MUL/min/mm Hg) and highest in BALB/cJ (0.0164 +/- 0.0059 MUL/min/mm Hg). Like IOP, C was intermediate in C57BL/6J (0.0147 +/- 0.0029 MUL/min/mm Hg). There was a strong correlation between conscious IOP and outflow resistance (1/C) from individual eyes across all three strains, revealing that 70% of the variation in IOP was attributable to variation in outflow resistance. CONCLUSIONS: Differences in IOP among three genetically distinct murine strains are attributable largely to differences in conventional outflow facility. These results motivate further studies using mice to identify the morphologic and genetic factors that underlie IOP regulation within the conventional outflow pathway. PMID- 24235016 TI - Extremely complex populations of small RNAs in the mouse retina and RPE/choroid. AB - PURPOSE: MicroRNAs (miRNAs) are small noncoding RNAs of approximately 18 to 22 nucleotides in length that regulate gene expression. They are widely expressed in the retina, being both required for its normal development and perturbed in disease. The aim of this study was to apply new high-throughput sequencing techniques to more fully characterize the miRNAs and other small RNAs expressed in the retina and retinal pigment epithelium (RPE)/choroid of the mouse. METHODS: Retina and RPE/choroid were dissected from eyes of 3-month-old C57BL/6J mice. Small RNA libraries were prepared and deep sequencing performed on a genome analyzer. Reads were annotated by alignment to miRBase, other noncoding RNA databases, and the mouse genome. RESULTS: Annotation of 9 million reads to 320 miRNAs in retina and 340 in RPE/choroid provides the most comprehensive profiling of miRNAs to date. Two novel miRNAs were identified in retina. Members of the sensory organ-specific miR-183, -182, -96 cluster were among the most highly expressed, retina-enriched miRNAs. Remarkably, miRNA "isomiRs," which vary slightly in length and are differentially detected by Taqman RT-qPCR assays, existed for all the microRNAs identified in both tissues. More variation occurred at the 3' ends, including nontemplated additions of T and A. Drosha-independent mirtron miRNAs and other small RNAs derived from snoRNAs were also detected. CONCLUSIONS: Deep sequencing has revealed the complexity of small RNA expression in the mouse retina and RPE/choroid. This knowledge will improve the design and interpretation of future functional studies of the role of miRNAs and other small RNAs in retinal disease. PMID- 24235017 TI - Allergy is a protective factor against age-related macular degeneration. AB - PURPOSE: To investigate the role of allergy on AMD. METHODS: Age-related macular degeneration staging was performed for 3585 individuals (1878 from Cologne, Germany, and 1707 from Nijmegen, The Netherlands). Interviewer-assisted questionnaires were evaluated for the factors smoking, use of corticosteroids, and history of allergy, including causative allergens. Serum complement component C3d and C3 levels were measured and the C3d:C3 ratio was calculated. Associations of allergy with AMD/late AMD were assessed by logistic regression analysis; C3d:C3 ratio was compared between groups. RESULTS: The discovery cohort from Cologne included 864 AMD patients and 1014 controls; 495 patients had late AMD. Positive history of allergy showed strong protective effects on the phenotype AMD (OR 0.52; P = 3.42 * 10(-9)) and late AMD (OR 0.32; P = 2.57 * 10(-13)). Subclassification in allergy-provoking agents showed significant protective effects in all groups. After adjustment for age, sex, smoking, and corticosteroid use, protective effects for AMD (OR 0.75; P = 0.018) and late AMD (OR 0.49; P = 2.87 * 10(-5)) were confirmed. Although the C3d:C3 ratio was higher in AMD/late AMD patients (both P < 0.001), there was no association with allergy in AMD (P = 0.22). The protective effect of allergy on AMD was confirmed in the replication cohort from Nijmegen (P = 0.002 for AMD; P = 0.0001 for late AMD). CONCLUSIONS: Allergy has a protective effect on the development of AMD independent of the provoking allergen, which cannot be explained by complement activation. Further investigations are necessary to elucidate the molecular mechanisms underlying the protective effect of allergy on AMD. PMID- 24235018 TI - Neural crest origin of retinal and choroidal pericytes. AB - PURPOSE: The origin of pericytes (PCs) has been controversially discussed and at least three different sources of PCs are proposed: a neural crest, mesodermal, or bone marrow origin. In the present study we investigated a potential neural crest origin of ocular PCs in a transgenic Rosa26-YFP-Sox10-Cre neural crest-specific reporter mouse model at different developmental stages. METHODS: The Rosa26-YFP Sox10-Cre mouse model expresses the yellow fluorescent protein (YFP) reporter in cells with an active Sox10 promoter and was here used for cell fate studies of Sox10-positive neural crest derived progeny cells. Detection of the YFP signal in combination with double and triple immunohistochemistry of chondroitin sulfate proteoglycan (NG2), platelet derived growth factor receptor beta (PDGFRbeta), alpha smooth muscle actin (alphaSMA), oligodendrocyte transcription factor 2 (Olig2), and lectin was performed and analyzed by confocal microscopy. RESULTS: Sox10-YFP-positive cells and profiles were detected in the inner nuclear layer, the ganglionic cell layer, and the axons of the nerve fiber layer in postnatal retinas. An additional population has been identified in the retina, optic nerve, and choroid that displays strong perivascular localization. These cells were colocalized with the PC-specific markers NG2 and PDGFRbeta in embryonic (E14.5) as well as postnatal (P4, P12, 6-week-old) vasculature. Beside PCs, vascular smooth muscle cells (vSMCs) were also labeled by the Sox10-YFP reporter protein in all ocular tissues investigated. CONCLUSIONS: Since YFP-positive PCs and vSMCs are colocalized with NG2 and PDGFRbeta, we propose that capillary PCs and vSMCs in the retina and the optic nerve, both parts of the central nervous system, as well as in the choroid, a tissue of mesodermal origin, derive from the neural crest. PMID- 24235019 TI - Dynamic low back functional motion capacity evaluation. AB - Most current functional capacity evaluations focus on range of motion and strength as measures of Wellness. The goal of this study was to evaluate the dynamic functional motion capacity of controls (those without low back pain) and low back pain patients in the three cardinal planes of the body. The hypothesis was that injury would not only affect sagittal motion but also lateral and twisting motion that would load the spine in a different manner. Twenty-six age and gender matched controls and low back pain patients were tested. Trunk motion parameters of range of motion (ROM), velocity, and acceleration were measured in all three planes of the body as subjects performed three separate tasks eliciting motion in each of the three cardinal planes of the body. Controls exhibited significantly higher performance than low back pain patients in all three planes of the body for velocity and acceleration but not ROM. Single parameter discriminant function models indicated that the velocity and acceleration motion parameters distinguished between LBP patients and the control group more effectively than ROM in the cardinal planes. Multiple parameter discriminant function demonstrated that coupled motion models further increased the ability to distinguish between the control and patient groups. These results provide insight into new methods of evaluating functional capacity using velocity, acceleration, and coupling which may provide valuable information in determining the recovery of a patient. PMID- 24235020 TI - Changes in psychopathology following functional restoration of chronic low back pain patients: A prospective study. AB - Past research has consistently demonstrated high rates of psychopathology in patients disabled with chronic low back pain. The purpose of the present study was to evaluate whether functional restoration treatment of these patients would lead to significant changes in psychopathology. Fifty-six patients were evaluated for current psychiatric disorders, using a structured clinical interview for DSM III-R disorders, upon admission to a comprehensive 3 week functional restoration program, and again at 6 months following their rehabilitation. Results clearly documented significant decreases in prevalence rates of psychiatric disorders, particularly somatoform pain disorder and major depression. Such findings demonstrate that effective rehabilitation can significantly decrease the high rates of psychopathology commonly found in chronic low back pain patients. PMID- 24235021 TI - Relationships among age, body weight, resting heart rate, and performance in a new test of lift capacity. AB - This study measured the relative contributions of age, gender, body weight, and resting heart rate to lift capacity in 531 healthy employed males and females in a cross-sectional model. The objectives of this study were to measure the contributions to lift capacity that are made by these variables and to develop an appropriate means to express the results of a new test of lift capacity. A formal training program was developed and administered to 110 health care professionals. Subsequently, each trained evaluator performed five tests on healthy volunteers. The effect of the independent variables were studied through the use of multiple regression and analysis of variance procedures. Results indicate that age, resting heart rate, and body weight are significant predictors of performance, with the last variable being the most important. A method to normalize lift capacity is presented in which the maximum acceptable weight lifted is divided by the evaluee's body weight to derive relative acceptable weight, a variable which is normally distributed. Those who use measures of lift capacity to describe performance must consider the effect of these variables in order to make valid interpretations of lift capacity test performance. PMID- 24235022 TI - A limited functional restoration program for injured workers: A randomized trial. AB - Worker's Compensation Board (WCB) claimants suffering from soft tissue injuries were treated in a limited functional restoration program (FRP) and compared to a randomized group of claimants referred back to their family doctors for "usual care." The FRP consisted of exercise, work conditioning, group education and behavioral counseling designed to maximize function, improve pain coping strategies, and ultimately return claimants to work. Results showed that treated claimants were significantly more likely to be back at work or "work ready" (in a job search, in retraining or school) 18 months posttreatment than claimants left to the "usual care" of their attending physicians. They also reported lower pain levels and improved sleep on follow-up. Claimants with low back pain were more successful in returning to work than those with nonback pain or multiple complaints. Results are discussed in terms of the need for better coordination of care to ensure positive outcomes, ideal features of a successful FRP and the need to better understand who will benefit from this intervention. PMID- 24235023 TI - Predicting post treatment spinal strength and flexibility in work-disabled low back pain patients. AB - This study examined whether posttreatment trunk strength and flexibility could be predicted from initial trunk strength and flexibility, age, gender, pain severity, diagnosis, length of work disability, return-to-work expectations, anxiety, and fear of reinjury among a group of 96 injured workers with chronic occupational low back pain who completed a multidisciplinary work rehabilitation program. The results indicate that initial average torque in trunk extension, age, gender, and average pain severity contribute significantly to prediction of final average torque in trunk extension. Initial average torque in trunk flexion, age, and gender contributed significantly to prediction of final average torque in trunk flexion, and age and initial range of motion contributed significantly to the prediction of final trunk range of motion. The results indicate that prediction of trunk strength and range of motion can be accomplished from measures of trunk strength and flexibility and pain obtained prior to the onset of rehabilitation. Psychological measures were not predictive of posttreatment trunk strength and flexibility. The ability to predict posttreatment trunk strength should facilitate clinical decision making in these complex cases. PMID- 24235025 TI - Tandem bullet injury: an unusual variant of an unusual injury. PMID- 24235026 TI - Reactive follicular lymphoid infiltrate: a new condition to exclude in patients with PET positivity inside the heart. PMID- 24235024 TI - The importance of autophagy in cardioprotection. AB - Autophagy is an intracellular lysosomal-mediated catabolic process in which senescent or damaged proteins and organelles are sequestered by double membrane limited vesicles called autophagosomes, and then degraded by lysosomes. While the role of autophagy in different pathological states is context-dependent, it has been shown that during cardiac ischemia, autophagy is upregulated as a cardioprotective adaptation. We recently demonstrated that Rheb, a small GTP binding protein that directly activates the complex 1 of the mechanistic target of rapamycin, is a critical regulator of autophagy during cardiac ischemia. We found that cardiac Rheb/mTORC1 signaling is activated in a deregulated manner during ischemia in obesity and metabolic syndrome. This uncontrolled activation of the Rheb/mTORC1 pathway leads to autophagy inhibition and to a reduction of myocardial tolerance to ischemia. This data further supports the relevance of autophagy as a fundamental protective mechanism during myocardial ischemia and suggests that reactivation of autophagy, in particular through the inhibition of Rheb/mTORC1 signaling may represent a promising therapeutic option to treat subjects with an acute myocardial infarction, particularly those affected by metabolic derangements. This review will deal with the biological significance of autophagy in cardioprotection. PMID- 24235027 TI - Scientific research and human rights: a response to Kitcher on the limitations of inquiry. AB - In his recent work exploring the role of science in democratic societies Kitcher (Science in a democratic society. Prometheus Books, New York, 2011) claims that scientists ought to have a prominent role in setting the agenda for and limits to research. Against the backdrop of the claim that the proper limits of scientific inquiry is John Stuart Mill's Harm Principle (Kitcher in Science, truth, and democracy. Oxford University Press, New York, 2001), he identifies the limits of inquiry as the point where the outcomes of research could cause harm to already vulnerable populations. Nonetheless, Kitcher argues against explicit limitations on unscrupulous research on the grounds that restrictions would exacerbate underlying social problems. I show that Kitcher's argument in favor of dissuading inquiry through conventional standards is problematic and falls prey to the same critique he offers in opposition to official bans. I expand the conversation of limiting scientific research by recognizing that the actions that count as 'science' are located in the space between 'thinking' and 'doing'. In this space, we often attempt to balance freedom of research, as scientific speech, against the disparate impact citizens might experience in light of such research. I end by exploring if such disparate impact justifies limiting research, within the context of the United States, under Title VII of the Civil Rights Act of 1964 or under international human rights standards more generally. PMID- 24235028 TI - Prevalence and impacts of low back pain among peasant farmers in south-west Nigeria. AB - OBJECTIVES: A relationship between low back pain (LBP) and poor postures has been previously established with a high prevalence observed in many occupations. This study aimed to investigate the prevalence of LBP, associated risk factors and impacts on farmers in South-West Nigeria. MATERIALS AND METHODS: Six hundred and four farmers completed a 36-item closed-ended questionnaire which was translated to Yoruba language with content validity and back translation done after-wards. The questionnaire sought information on demographic data, 12-month prevalence, severity, history, causes and management of LBP, and its impacts on farm activities and the activities of daily living. Data was analyzed using the Statistical Package for Social Sciences (SPSS) version 17. Data was summarized using descriptive statistics of mean, range, frequency, standard deviation, percentage. Chi2 and Mann-Whitney-U test were used to find association between variables. The level of significance was set at alpha = 0.05. RESULTS: The 12 month prevalence of LBP among the respondents was 74.4%. Low back pain was described as moderate in 53.4%. Prolonged bending (51.3%) was the most related risk factor. A consider-able proportion (65.9%) of the respondents were unable to continue some of the previously enjoyed activities. Males had significantly higher (p < 0.05) prevalence, recurrence and duration of LBP than the females. CONCLUSION: There is a high prevalence of LBP among farmers in South-West Nigeria. Age, sex and years of involvement in farming have a significant influence on the prevalence of LBP. PMID- 24235030 TI - The quest for literacy. PMID- 24235029 TI - A tribute to Sally Childs. PMID- 24235031 TI - Helping dyslexics-A task for sharing. PMID- 24235032 TI - Is there a thing called dyslexia? AB - A controversy whether developmental dyslexia is qualitatively different from other forms of reading disability has existed among reading specialists for many years because poor readers, regardless of the labels attached to them, resemble each other symptomatically (i.e., in reading achievement). For this reason, it is difficult to establish a priori criteria based on symptoms to identify dyslexia and compare it with other forms of reading disability. One possible solution to this impasse is to see if poor readers differ in the etiology of their reading disability and, if they do, then to see whether one group of poor readers fits the traditional definition of dyslexia. This strategy was adopted in the present study. In this paper, it was hypothesized that the etiology of dyslexia is different from that of other forms of reading disability because there is a difference in the components that malfunction in dyslexia and other forms of reading disability. Studies have shown that the two components that account for a large proportion of variance in reading are decoding and comprehension. Previous studies also indicate that dyslexic children are deficient in decoding skills but not necessarily in comprehension. In this study, reading-disabled children were divided into two groups on the basis of their listening comprehension. Children whose listening comprehension was at or above grade level were placed in one group; poor readers with below-grade-level listening comprehension were placed in the second group. Both groups, however, were matched for reading comprehension. The two groups and a control group of normal readers were administered a number of tasks that were designed to assess the efficiency of the components of reading. It was found that poor readers with normal listening comprehension were deficient in tasks that involved grapheme-phoneme conversion (Component I, decoding). When tested on tasks that minimized decoding requirements, their reading comprehension was comparable to that of normal readers. In contrast, the group with sub-average listening comprehension was poor in measures of reading comprehension, even when decoding requirements were minimal. With the exception of very few children, this group also had adequate decoding skills. Because poor readers with normal listening comprehension had average or above average IQ, they conform to the traditional definition of dyslexia. Poor readers with below average listening comprehension had below average IQ and could be considered as "general reading backward." It was, therefore, concluded that the etiology of developmental dyslexia is different from that of general reading backwardness. PMID- 24235033 TI - Naming ability and oral fluency in dyslexic adolescents. AB - Twenty-one dyslexic boys, aged between 113/4 and 18, were presented with drawings of familiar objects and asked to name the part of the object to which an arrow pointed, for example the flex of an iron and the mane of a horse. They were also asked to explain the meanings of six words with only one meaning, six homophones (pier/peer), and six homographs (bat/bat). Nineteen control boys from the same background were also given the tests. No time constraints were imposed.It was found that the dyslexics were no less successful than the controls in finding the names for the parts of the objects and that they had no distinctive difficulty over homophones or homographs. However, when an analysis of errors was carried out, it was found that, in comparison with the controls, they produced more distortions of words (for instance bucker for buckle), gave fewer "don't know" responses, and showed a greater tendency to repeat the parent word. In the case of the word-explanation tasks, they produced more examples of inappropriate usage (for example, in response to pier, "is what people walk along and fishing off"), more incomplete sentences, more repetitions, more misunderstandings of words, and more unnecessary amplifications of their original response. There was an equal tendency in both groups to ignore the indefinite article (for example, a bat. What is a bat?-"To bat a ball"). The dyslexics used fewer relative clauses, and there was marginal evidence for more frequent use of you and your and of er, um, and well.It is argued that among dyslexic adolescents, there remains a residual uncertainty which affects their oral language, and it is suggested that teachers should pay more attention to this weakness, since if a pupil cannot express himself adequately in speech, he is likely to show similar difficulties in his written work. PMID- 24235034 TI - Grammaticality judgments and reading skill in grade 2. AB - Do the language problems associated with reading disability extend to sentence level knowledge? If so, how should these problems be characterized? In this study, second graders were presented with two different oral syntactic tasks, equivalent in grammatical complexity, but varying in the actual task demands placed upon the reader. In theJudgment task, subjects were asked to distinguish between grammatical and ungrammatical sentences; in theCorrection task, subjects were asked to remedy violations of grammaticality. Performance on these sentence level tasks was, in turn, examined in relation to reading scores, memory span, and metaphonological skill. The Judgment task revealed a wide range of ability among second-graders, and scores were systematically affected by the syntactic nature of the violation. However, performance on Judgment was not associated with reading ability or metaphonological skill, and scores were minimally affected by short-term memory factors. Mean scores on the Correction task were comparable to those achieved in the Judgment task and were also systematically affected by syntactic factors. However, performance on Correction was strongly associated with reading ability and metaphonological skill, and was greatly affected by short-term memory factors. These results suggest that reading disability does not reflect problems in basic syntactic knowledge. Instead, sentence-level problems that have been observed in less-skilled readers may be caused by the nonlinguistic processing demands of the syntactic measures typically employed. PMID- 24235035 TI - A componential approach to understanding reading and its difficulties in preadolescent readers. AB - The present study is predicated on the logic of interrelated functional information processing components as an approach to understanding reading and its difficulties in preadolescent readers. The structural equation modelling (and its variants) involved these three latent components: (a) orthographic/phonological component, (b) morphological component, and (c) sentence and paragraph comprehension component. These components were subserved by a total of ten measurable tasks, all administered on-line via the microcomputer under laboratory conditions with reaction time measures as indices of mental representation of word knowledge and sentence/paragraph comprehension. The latent dependent component of reading performance was subserved by standardized vocabulary and reading comprehension tests. The total sample consisted of 298 children in grades, 4, 5, and 6. Maximum likelihood analyses using LISREL show that the data in general do not disconfirm the proposed model for grade 4 readers. The three component model, with some variables set free, provides a reasonable fit for the grade 5 data but less claim could be made about the goodness of fit for grade 6. The results show the mutually reinforcing and mutually facilitating effects of multilevels and multicomponents of reading. Word structure and word knowledge are particularly predictive of reading. The present Phase 1 work would be validated in a follow-up of another cohort of readers and would also lead to the systematic training of some of the components with poor readers. PMID- 24235036 TI - Colorado reading project: Longitudinal analyses. AB - Extensive psychometric test data were obtained from two independent samples of reading-disabled and control children: 70 probands and 75 controls tested on two occasions over an average interval of 4.2 years, and 35 probands and 22 controls tested on three occasions over an average interval of 8.6 years. When composite measures of reading performance and symbol-processing speed were subjected to mixed-model multivariate analyses of variance, significant effects due to group (reading-disabled versus control) and time (i.e., test session) were obtained in both samples, and a significant group-by-time interaction was obtained for the sample tested on three occasions. In general, rates of change in reading performance are highly similar for reading-disabled and control children. However, with regard to symbol-processing speed, differences between the two groups increase as a function of age. Although no evidence was obtained for differential longitudinal stability of either composite measure in reading disabled and control children, results of a multiple regression analysis suggest that reading deficits during middle childhood are highly predictive of later reading problems, even into early adulthood. PMID- 24235037 TI - Genetic and environmental etiologies of reading disability: A twin study. AB - Previous twin studies of reading disability employed a comparison of concordance rates in identical and fraternal twin pairs as a test for genetic etiology. Recently, a statistically more powerful multiple regression analysis of twin data has been formulated to assess the importance of genetic factors in the development of reading difficulties. Application of this analysis to twin data from the Colorado Reading Project yields definitive evidence for a genetic etiology. Results from this study suggest that approximately 40 percent of the deficit observed in the disabled readers is due to genetic factors, 35 percent is due to environmental influences shared by members of twin pairs, and about 25 percent is the result of environmental factors unique to the individual and/or error variance. PMID- 24235038 TI - A developmental perspective on dyslexic subtypes. AB - In this paper we apply a developmental model of reading to the question of dyslexic subtypes. Groups of normal readers (n=40) and dyslexic children (n=50), matched on reading level and IQ, were given a comprehensive test battery measuring level of development of visual, phonological, and orthographic skills. As a group, dyslexics deviated from normal readers of equivalent reading achievement primarily in phonological skills (spelling-to-sound translation and phonemic analysis), although limited differences in knowledge of word-specific spellings were also observed. Dyslexics were superior to the younger normal readers in visual processing of print. Analysis of individual data by reference to the reading level control group revealed three major subgroups: a group with a specific deficit in phonological processing of print (52 percent), a group with deficits in processing both the phonological and orthographic features of printed words (24 percent), and a group with phonological deficits in language (8 percent). The remainder of the sample (16 percent) had specific deficits in visual or orthographic processing of print, in spelling, or did not differ from the control group. The data support the view that most developmental dyslexics have a specific language disorder involving some aspect of phonological processing. However, small subgroups with very different configurations of reading and nonreading difficulties may exist as well. PMID- 24235039 TI - The right and wrong places to look for the cognitive locus of reading disability. AB - A coherent conception of dyslexia has been difficult to arrive at because research findings have continually created logical paradoxes for the psychometric definition of reading disability. One such paradox is that cognitive research has undermined the assumption of specificity in the definition of dyslexia. The assumption of specificity is the underlying premise that the cognitive problems characteristic of the dyslexic child are reasonably specific to the reading task and do not implicate broader domains of cognitive functioning. This paper demonstrates how to develop hypotheses about the cognitive deficits of dyslexic children that do not undermine the assumption of specificity. Phonological awareness is explored as one candidate process.It is argued that in order to avoid the pitfalls surrounding the assumption of specificity three things are important: 1) We must understand the operation of Matthew effects in education (rich-get-richer and poor-get-poorer effects); 2) Strict psychometric criteria must be used to define dyslexia; 3) We must continually be aware that dyslexia does not demarcate a discrete category, separate from other groups of poor readers, but represents the outcome of the application of an arbitrary criterion in a continuous distribution. PMID- 24235040 TI - Screening for reading problems: The utility of SEARCH. AB - To evaluate the accuracy of SEARCH as a screen for identifying children at risk for developing learning problems, 1107 kindergarten children were evaluated with SEARCH and 284 (26 percent) were classified as at risk. At-risk children were of average intelligence and SEARCH scores were significantly correlated with sequential and simultaneous information processing skills. Children whose group preacademic achievement scores were at or below the third stanine at the end of kindergarten were classified as having inadequate skills for learning how to read; those scoring above the third stanine formed the adequate skills group. Using this criterion, SEARCH predicted children who had adequate or inadequate preacademic reading skills with 77 percent accuracy. However, approximately half of the children identified as at risk by SEARCH performed adequately. A reading test was individually administered to a group of at-risk children at the end of first (N=49) and second (N=35) grade. Of those children identified at risk by SEARCH at kindergarten, 39 percent at first grade and 66 percent at second grade performed at grade level. Fewer children from the upper SES were identified by SEARCH as being at risk. PMID- 24235041 TI - A classroom-based model of language intervention for preschool language-impaired children: Principles and procedures. AB - It is now generally recognized that a language impairment in preschool children may be predictive of later linguistic, reading, and academic difficulties. Language intervention procedures, derived from theoretically-based principles of language development and implemented in a child's regular classroom environment, may benefit children at risk for persistent language and learning problems. This paper describes the development and application of individualized intervention procedures in a classroom for preschool language-impaired children. The discussion focuses on selected language development principles which helped determine the setting, timing, interactive participants, purpose, and content of the language intervention program. Resulting changes in language comprehension and production are reported based on individual classroom performance as well as a comparison of pre-and posttest scores for a range of comprehension skills. PMID- 24235042 TI - Phoneme segmentation training: Effect on reading readiness. AB - Recent evidence suggests that the ability to segment words into phonemes is significantly related to reading success, and that training in phoneme segmentation appears to have a positive influence on beginning reading. In this study, we evaluated the effect on reading readiness of phoneme segmentation training in kindergarten. Ninety nonreaders with PPVT-R standard scores of 78 or higher were randomly selected from six kindergarten classrooms and assigned to one of three treatment conditions: a) phoneme segmentation group; b) language activities group (control group I); and c) no intervention (control group II). The phoneme segmentation group received seven weeks of instruction in segmentation and in letter names and sounds. Also for seven weeks, the language activities group received the identical instruction in letter names and sounds and additional language activities. Prior to the intervention, the three groups did not differ in age, sex, race, PPVT-R phoneme segmentation, letter name and letter sound knowledge, or reading ability. After the intervention, the phoneme segmentation group outperformed both control groups on phoneme segmentation and reading measures. This study provides additional strong support for including phoneme segmentation training in the kindergarten curriculum. Clinical suggestions for teachers are included. PMID- 24235043 TI - Syllable division: Prerequisite to dyslexics' literacy. AB - Skill in reading long words is prerequisite to dyslexics' literacy. Instant recognition of printed symbols is easy for those readers with photographic memories, but dyslexics often fail to recognize visually many long words which are actually familiar to them auditorially. Scientific, automatic, multisensory procedures for dividing longer words into easily read syllables can enable students to translate visual symbols rapidly and thereby to read, write, or spell accurately words of any length.Over one thousand dyslexics, aged seven to fifteen, guided the interdisciplinary team at Texas Scottish Rite Hospital in Dallas to develop, observe results, and test specific structured, sequential steps in working out longer words. The ten-year study (1965-1975) in the Language Laboratory of the Hospital established the Alphabetic Phonics curriculum which is now used successfully, not only in remedial groups but in regular classes of any size or age, in public and private schools in 45 states and six foreign countries.The newly-established Aylett Royall Cox Institute in Dallas prepares teachers and Master Instructors to train both students and other teachers. Comparable Alphabetic Phonics Teacher Training Centers are already established in Houston and Lubbock, Texas, in Oklahoma City, and at Columbia University Teachers College in New York. PMID- 24235044 TI - Beyond decoding: Pictures of expository prose. AB - Just as success in decoding complex spelling patterns requires strategy and structure, so does the "decoding" of complex expository writing. We discuss the specific sources of difficulty in technical writing and distinguish between content structure and text structure. Next come presentations of the basic building blocks for expository writing and techniques of text design. Patterns from American science and social studies texts are described and contrasted with Japanese materials. We finish with suggestions for promoting the comprehension of expository materials. PMID- 24235045 TI - Beyond phonics: Integrated decoding and spelling instruction based on word origin and structure. AB - In this paper, the relevance of word structure knowledge to decoding and spelling instruction is discussed. An explicit, discussion oriented, direct approach to teaching decoding and spelling based on word origin and structure results in improved reading and spelling. This instruction leads students to a comparison and contrast of letter-sound correspondences, syllable patterns, and morpheme patterns in English words of Anglo-Saxon, Romance, and Greek origin. PMID- 24235047 TI - Foreword. PMID- 24235046 TI - Dyslexic/learning disabled students at Dartmouth college. AB - Dartmouth College, a highly selective Ivy League college with 4100 undergraduates, has a small but significant number of dyslexic/learning-disabled students, two-thirds of whom were identified through diagnostic testing at Dartmouth. Close advising relationships and intensive interviews with Dartmouth learning-disabled students reveal a profile of a particular category of learning disabled college students. In spite of experiencing difficulty in a specific content area or with an information-processing task, learning-disabled Dartmouth students achieve well academically, socially, and extracurricularly, get high scores on timed SAT and IQ tests, and rely when necessary on accommodations, rather than remedial courses or specialized tutorial assistance.The authors surveyed selective colleges in 1986 and 1988 and found an increase in awareness and academic accommodations at other selective colleges during this two-year period. A 1987 dyslexic/learning-disabilities symposium hosted by Dartmouth is described, as are Dartmouth's services and accommodations. The authors provide a suggested list of services and resources for highly selective colleges. PMID- 24235048 TI - Environmental management strategies : A new feature in ESPR. PMID- 24235049 TI - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and related compounds: Update and recent developments. PMID- 24235050 TI - Formation of PCDD/PCDF : Effect of fuel and fly ash composition on the formation of PCDD/PCDF in the co-combustion of refuse-derived and packaging-derived fuels Multivariate analysis. AB - One option of recycling used contaminated packaging is to recover its high energy content. This can be performed in a normal multi-fuel power plant by co combustion of packaging-derived fuel (PDF) or refuse-derived fuel (RDF) with fossil fuels, such as coal or peat. This work includes the results of 17 co combustion tests and an evaluation of the results by the Principal Component Analysis (PCA) and the Partial Least Squares Projections to Latent Structures (PLS).PCA and PLS calculations showed that especially Pb, but also Cr, and Cu correlated with lower chlorinated furans (PCDFs) in the fly ash. Correlation between Sn and lower chlorinated dioxins (PCDDs) in the fly ash was also noticed. CO and PAH emission in the flue gas correlated with total PCDD/Fs in the flue gas. In a real full-scale combustion process, a single parameter in fuel, flue gas or a combustion parameter did not provide a guide to PCDD/F formation or to a level of the total PCDD/F emission, but correlations between different parameters and PCDD/Fs could be found. Although PDFs and RDF had catalytic heavy metals and chlorine, the co-combustion results showed that they can be co-combusted with peat and coal in a fluidized-bed boiler at least up to 26 % with very low total PCDD and PCDF emissions. PMID- 24235051 TI - Uptake of nitroaromatic compounds in plants : Implications for risk assessment of ammunition sites. AB - The uptake of nitroaromatic compounds by plants from the soil was studied at an ammunition site. After the development of analytical methods for 2,4,6 trinitrotoluene, aminodinitrotoluenes and dinitrotoluenes in plant material, we could show that these substances accumulated in the roots of plants and are found to a lesser extent inleaves and stems. We observed only moderate differences between various plant species. It is likely that a metabolic transformation in plants leads to the formation of dinitrotoluenes which are considered to be potent carcinogens. Results from soils with a wide range of explosive concentrations show a good correlation between the plant and soil concentrations. The relative accumulation in plant material is higher at lower soil concentrations. At low soil concentrations of about 1 mg trinitrotoluene/kg soil, an accumulation factor of about 0.5 can be derived. These data are an important input for the risk assessment of ammunition sites. PMID- 24235052 TI - Multiple chemical sensitivity (MCS) : Idiopathic environmental intolerances (IEI). AB - Multiple Chemical Sensitivity (MCS) is a systemic disorder causing central nervous, irritative and gastrointestinal symptoms, and can be included in the category of "idiopathic environmental intolerance" (IEI). This term describes phenomena with multiple, recurrent symptoms associated with various environmental factors that are tolerated by most people without problems. Those advocating these concepts attribute the symptoms to exogenous substances. Those opposing them explain the phenomena by classical conditioning or other psychopathological processes. To the extent that controlled studies are available, they have not furnished any hard evidence for toxic or immunological causes. In addition to psychopathological origins, neurobiological processes are also implicated. PMID- 24235053 TI - Ozone and grosswetterlagen : Analysis for the Munich Metropolitan Area. AB - Meteorological conditions have a decisive impact on surface ozone concentrations. In this study, an empirical model is used to explain the interdependence of ozone and grosswetterlagen. Different meteorological parameters such as air temperature, global solar radiation, relative humidity, wind direction and wind speed are used. Additional nitric oxide (NO) was taken as a representative for the emission situation and ozone maximum of the preceding day in order to evaluate the development of the photochemical situation. The dataset includes data collected over a period of three years (1992-1994) from three stations outside of Munich and one in the center of Munich.All values become variables by calculating means, sums or maxima of the basic dataset consisting of half-hour means. Seasonal periodicity of data is detected with Fourier analysis and eliminated by a division method after computing a seasonal index.The dataset is divided into three different grosswetterlagen groups, depending on main wind direction. One mostly cyclonic (westerly winds), onemixed (alternating winds) and one onlyanticyclonic (easterly winds). The last is completed with one summertime group including values from April to August.Factor analysis is performed for each group to obtain independent linear variable combinations. Overall, relative humidity is the dominant parameter, a typical value indicating meteorological conditions during a grosswetterlage.Linear multiple regression analysis is performed using the factors obtained to reveal how the ozone concentrations are explained in terms of meteorological parameters and NO. The results improve from cyclonic to anticyclonic grosswetterlagen in conformance with the increasing significance of photochemistry, indicated by the high solar radiation and high temperature, and the low relative humidity and low wind speed. The explained variance r(2) reaches its maximum with more than 50 % of the time in Munich center.This empirical model is applicable to the forecasting of local ozone maximum concentrations with a total standard error deviation of 8.5 to 12.8 % and, if ozone concentrations exceed 80 ppb, with a standard error deviation of 5.4 to 9.5 %. PMID- 24235054 TI - Global total ozone dynamics : Impact on surface solar ultraviolet radiation variability and ecosystems Part I: Global ozone dynamics and environmental safety (ESPR 3/96) Part II: Dynamics of atmospheric chemical composition: The role of remote sensing (ESPR 4/96). AB - An overview of the ozone issues is given including the following aspects: 1. The impact of tropospheric ozone on climate as a greenhouse gas (GHG), 2. Solar activity effects on TO and ozone concentration vertical profiles in both the troposphere and stratosphere (in cases of solar radiation absorption by the stratosphere, an unexpected problem arises via a coupling between processes of increased absorption due to "bursts" of solar activity and an enhanced destruction of ozone molecules due to the same increase resulting in weakening UV radiation absorption) and 3. Surface ozone concentration variations under conditions of polluted urban atmospheres which lead to episodes of photochemical smog formation (dangerous for human health). PMID- 24235055 TI - XVIII Quadrennial ozone symposium : L'Aquila/Italy 12-21 September 1996. PMID- 24235056 TI - Secondary air pollutants : Epistomatal wax erosion of Scots pine needles. AB - The study has been performed in a supposedly clean-air region of a Northern Finnish forest with a homogeneous stand of Scots pine. Stomatal epicuticular wax layer erosion is described using a classification system of five erosion stages. The percentage of stomatal wax within each erosion stage is calculated and the results are treated statistically, which makes the morphological study of the needle surface semi-quantitative. Severe wax degradation has already been found in the current year, increasing with the age of the needles. In this area, the wax layer erosion is correlated with secondary air pollutants, as analyses have shown high trichloroacetate (TCA) levels in needles from the same trees. The wax layer analyses are in accordance with earlier findings which have demonstrated differences in tolerance to TCA. PMID- 24235057 TI - Hydrophobicity of complex organic mixtures. AB - Hydrophobicity is an important property in risk assessment of chemicals. A group parameter that reflects the hydrophobicity of technical mixtures is not yet available. However, many substances are complex organic mixtures, for which it is practically impossible to determine each component separately. An experimental procedure to measure the hydrophobicity of organic mixtures without knowledge of the individual components was developed and tested for a mixture of benzene and twelve chlorobenzenes. This procedure is based on separation of the mixture into fractions of increasing hydrophobicity by reversed-phase HPLC, after which the total molar concentration in each fraction is determined by vapour pressure osmometry. The obtained information on hydrophobicity can be used for assessing bioaccumulation and sediment sorption after emission of the mixture to water has occurred. PMID- 24235058 TI - Biomonitoring and environmental specimen banking. AB - The environmental specimen banking program (ESB) of the Federal Republic of Germany implies a collection of specimens from representative areas of Germany, stored under stable conditions for deferred analysis. It is an important part of the ecological assessment program. The ecological concept is presented as the frame of the entire ESB program. It is based on the selection of representative sampling areas and specimens. Standard operating procedures (SOP's) for sampling and characterization of specimens, as well as sampling designs specific to the areas, are presented as further important parts of the quality assurance system in relation to the correct sampling of specimens. PMID- 24235059 TI - UNEP/IFCS Meeting on Persistent Organic Pollutants (POPs) : Manila, Philippines, 17 to 22 June 1996. PMID- 24235061 TI - Novel role of ZmaNAC36 in co-expression of starch synthetic genes in maize endosperm. AB - Starch is an essential commodity that is widely used as food, feed, fuel and in industry. However, its mechanism of synthesis is not fully understood, especially in terms of the expression and regulation of the starch synthetic genes. It was reported that the starch synthetic genes were co-expressed during maize endosperm development; however, the mechanism of the co-expression was not reported. In this paper, the ZmaNAC36 gene was amplified by homology-based cloning, and its expression vector was constructed for transient expression. The nuclear localization, transcriptional activation and target sites of the ZmaNAC36 protein were identified. The expression profile of ZmaNAC36 showed that it was strongly expressed in the maize endosperm and was co-expressed with most of the starch synthetic genes. Moreover, the expressions of many starch synthesis genes in the endosperm were upregulated when ZmaNAC36 was transiently overexpressed. All our results indicated that NAC36 might be a transcription factor and play a potential role in the co-expression of starch synthetic genes in the maize endosperm. PMID- 24235062 TI - Type 2 diabetes mellitus in pediatrics: a new challenge. AB - BACKGROUND: The increased prevalence of childhood obesity in the last few years has been accompanied by the increase in prevalence of type 2 diabetes in pediatrics. In this paper, we will review the risk factors and the pathogenic determinants leading to type 2 diabetes in youth. DATA SOURCES: We searched on PubMed with the key words: obesity, type 2 diabetes, children, adolescents, youth, non-alcoholic fatty liver disease, genes and selected those publications written in English that we judged to be relevant to the topic of the review. RESULTS: Based on the data present in the literature, we reviewed the following three topics: 1) the role of ectopic fat deposition, in particular of fatty liver, in the pathogenesis of pediatric type 2 diabetes; 2) the progression to type 2 diabetes in pediatrics and how it differs from adults, and 3) current theraputic options. CONCLUSION: Type 2 diabetes in youth is a complex disease, creating new challenges in treatment and prevention. PMID- 24235063 TI - The association between hypertensive disorders in pregnancy and bronchopulmonary dysplasia: a systematic review. AB - BACKGROUND: Whether hypertensive disorders in pregnancy (HDP) are the risk factors of bronchopulmonary dysplasia (BPD) is controversial. A systematic review was made to determine the association between HDP and BPD in preterm infants. METHODS: We searched PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, with no language limitation, and reviewed the reference lists of the selected articles to identify additional relevant publications and contacted the authors of relevant studies for further information. The data were extracted independently by 2 reviewers who used a predetermined data extraction form. Studies were combined with an odds ratio (OR) using a random-effects model. Meta regression and subgroup analysis were used to explore potential confounders. Funnel plots, Egger's test and Begg's test were used to investigate the publication bias. The Trim and Fill method was used to control the publication bias. RESULTS: A total of 787 studies were identified and only 15 studies (20 779 patients) were included. The pooled unadjusted OR showed that HDP was significantly associated with BPD (P=0.04; OR=1.29, 95% CI=1.01-1.65). Heterogeneity was substantial (I(2)=74%) and might be partially explained by different variables in maternal complications between the control groups across the studies. The pooled adjusted OR suggested the same conclusion that HDP was a risk factor for BPD (P=0.01; OR=1.59, 95% CI=1.11-2.26). Funnel plot and Egger's test showed that there were publication bias of unadjusted estimate of association between HDP and BPD. CONCLUSIONS: Unadjusted analyses showed that the rate of BPD was slightly higher in the infants exposed to HDP, and adjusted analyses confirmed this finding. But this result should be interpreted cautiously because substantial heterogeneity and publication bias were identified in this review. PMID- 24235064 TI - Effects of supervised exercise program on metabolic function in overweight adolescents. AB - BACKGROUND: Inactivity is a primary factor related to childhood obesity, yet aerobic exercise has been shown to prevent weight gain and improve fitness in adolescents. Moreover, children become less active during their summer break from school. This study compared the effects of 4 and 8 weeks of supervised summer activity versus an unsupervised summer break on metabolic function and fitness in adolescents. METHODS: Twenty-two adolescents were divided into 4-week (n=6, weight 48.1+/-14.9 kg, body fat 27.4+/-8.4%) and 8-week exercise groups (n=6, weight 43.4+/-10.9 kg, body fat 28.5+/-12.8%), that performed supervised, play based physical activity, versus an age-matched 8 week control group that maintained their typical summer break (n=10, weight 41.7+/-10.0 kg, body fat 23.7+/-8.0%). Anthropometrics, resting energy expenditure (REE), resting heart rate (RHR) and peak aerobic capacity (VO(2peak)) were evaluated before and after the intervention (4 or 8 weeks). RESULTS: REE showed group differences in posttraining conditions (the 4-week group vs. the control group, 1220+/-169 vs. 1067+/-144 kcal/die, and the 8-week group vs. the control group, 1202+/-151 vs. 1067+/-144 kcal/die, P=0.047), but RHR decreased (pre-program vs. post program: 97+/-22 vs. 80+/-8 beat/min, P=0.001) and VO(2peak) significantly increased (pre program vs. post program: 27.8+/-7.8 vs. 34.8+/-6.5 mL/kg/min, P=0.001) in the 8 week group compared to the control group. CONCLUSIONS: Eight weeks of supervised play-based activity increased REE and VO(2peak) in adolescents with concomitant decreases in RHR. These data suggest that this novel model of exercise prescription could be considered world-wide by clinicians to improve fitness base in adolescents and help to combat the growing epidemic of childhood obesity. PMID- 24235065 TI - Psychological, cognitive and maternal stress assessment in children with primary ciliary dyskinesia. AB - BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder due to structure and functional abnormalities of respiratory cilia. There are no reports on the behavioral and psychological aspects of children and adolescents with PCD. This study was undertaken to assess the cognitive and behavioural characteristics, and the parental stress of a population of school-aged children with PCD. METHODS: Ten PCD and 34 healthy school-aged children underwent Wechsler Intelligence Scale for Children-III edition, Child Behavior Check-List questionnaire (CBCL), Parenting Stress Index-Short Form tests in order to perform a behavioural and psychological evaluation. RESULTS: PCD children showed significant behavioral and social competent problems in CBCL scale than control children, in particular with regard to internalizing problems score (P<0.001). Parental distress, parent-child interaction and total stress in the mothers of PCD patients were higher than those in the controls' parents (P<0.001). CONCLUSION: Our findings pinpoint the importance of specific psychological support in the clinical management of children with PCD. PMID- 24235066 TI - Acute kidney injury in a single neonatal intensive care unit in Turkey. AB - BACKGROUND: Although advances in perinatal medicine have increased the survival rates of critically ill neonates, acute kidney injury (AKI) is still one of the major causes of mortality and morbidity in neonatal intensive care units. This study aimed to determine the prevalence of AKI and analyze demographic data and risk factors associated with the mortality or morbidity. METHODS: Of 1992 neonates hospitalized between January 2009 and January 2011, 168 with AKI were reviewed in the study. The diagnosis of AKI was based on plasma creatinine level >1.5 mg/dL, which persists for more than 24 hours or increases more than 0.3 mg/dL per day after the first 48 hours of birth while showing normal maternal renal function. RESULTS: The prevalence of AKI was 8.4%. The common cause of AKI was respiratory distress syndrome, followed by sepsis, asphyxia, dehydration, congenital anomalies of the urinary tract, congenital heart disease, and medication. The prevalence of AKI in neonates with birth weight lower than 1500 g was about three-fold higher than in those with birth weight higher than 1500 g (P<0.05). Pregnancy-induced hypertension, preterm prolonged rupture of membranes, and administration of antenatal corticosteroid were associated with increased risk of AKI (P<0.05). Umbilical vein catheterization, mechanical ventilation and ibuprofen therapy for patent ductus arteriosus closure were found to be associated with AKI (P<0.05). The overall mortality rate was 23.8%. Multivariate analysis revealed that birth weight less than 1500 g, mechanical ventilation, bronchopulmonary dysplasia, anuria, and dialysis were the risk factors for the mortality of infants with AKI. CONCLUSIONS: Prenatal factors and medical devices were significantly associated with AKI. Early detection of risk factors can reduce the mortality of AKI patients. PMID- 24235067 TI - Efficacy and safety of serial injections of botulinum toxin A in children with spastic cerebral palsy. AB - BACKGROUND: Botulinum toxin A (BTX-A) has been successfully used as a treatment for children with spastic cerebral palsy; however, the effect of BTX-A on reducing spasticity only lasts a few months, thus serial injections are required. The present study was to evaluate the efficacy and safety of serial injections of BTX-A in children with spastic cerebral palsy. METHODS: Fifty-two pediatric patients with spastic cerebral palsy, 2-12 years of age (mean age, 4.79 +/- 2.70), were retrospectively analyzed. Muscle tone was assessed with the Modified Ashworth Scale, and gait was assessed with the Physician Rating Scale. Assessments were undertaken at baseline, 3 months, and 6 months after serial injections of BTX-A. RESULTS: The beneficial effects of BTX-A occurred 1 week after the injection, whereas the adverse side-effects appeared within 1 week and lasted <2 weeks. BTX-A significantly improved muscle tone and gait 3 and 6 months after its serial injections compared to baseline (P <0.05). CONCLUSIONS: Serial injections of BTX-A are effective and safe for children with spastic cerebral palsy. The sideeffects of serial injections of BTX-A are mild and selflimited. PMID- 24235068 TI - Clinical characteristics of adenovirus associated lower respiratory tract infection in children. AB - BACKGROUND: Acute lower respiratory tract infection (ALRI) due to adenovirus infection is a low frequency event but often causes severe outcome. This study was undertaken to uncover the clinical and epidemiological features of adenovirus infection in children. METHODS: Hospitalized children with ALRI were analyzed through continuous monitoring from 2006 to 2012. Nasopharyngeal aspirates were examined by direct immunofluorescence to detect respiratory agents including respiratory syncytial virus, adenovirus, influenza virus types A/B, parainfluenza virus types 1/2/3. Chlamydia pneumonia, Mycoplasma pneumonia and Chlamydia trachomatis were determined by real-time PCR. A retrospective analysis was made of 479 patients with positive infection of adenovirus. RESULTS: The positive detection rate of adenovirus was 0.63% in patients with ALRI. The incidence rate of adenovirus-associated acute lower respiratory tract infection peaked at the second six months of life. The morbidity was much higher in winter, spring and summer than in autumn. Patients with pneumonia accounted for 73.90% of the patients. More than one-third of the patients developed severe pneumonia, whereas no death was found. Features of severe adenovirus-associated lower respiratory tract infection included persistent high fever with serious infective symptoms, and hepatic dysfunction was one of the most common complications. Mixed infection of atypical pathogens was common (18.58%) in this study. CONCLUSIONS: Adenovirus is a critical pathogen that can cause severe respiratory infections even in immunocompetent children. Coinfection of adenovirus with atypical pathogens is common. Antibiotic treatment with azithromycin or erythromycin is necessary in patients with mixed infection of atypical pathogens. PMID- 24235069 TI - Effect of thimerosal on the neurodevelopment of premature rats. AB - BACKGROUND: This study was undertaken to determine the effect of thimerosal on the neurodevelopment of premature rats. METHODS: Thimerosal was injected into premature SD rats at a dose of 32.8, 65.6, 98.4 or 131.2 MUg/kg on postnatal day 1. Expression of dopamine D4 receptor (DRD4) and serotonin 2A receptor (5-HT2AR), apoptosis in the prefrontal cortex on post-injection day 49, and learning and memory function were studied and compared with those in a control group injected with saline. RESULTS: Expression of DRD4 and 5-HT2AR and learning function decreased, and apoptosis increased significantly in the 131.2 MUg/kg group (P<0.001). Memory function was significantly impaired by 65.6 (P<0.05), 98.4 and 131.2 MUg/kg (P<0.001). CONCLUSIONS: The negative adverse consequences on neurodevelopment observed in the present study are consistent with previous studies; this study raised serious concerns about adverse neurodevelopmental disorder such as autism in humans following the ongoing worldwide routine administration of thimerosalcontaining vaccines to infants. PMID- 24235070 TI - Ventilator-associated pneumonia in an Italian pediatric intensive care unit: a prospective study. AB - BACKGROUND: This study was undertaken to determine the prevalence, risk factors and outcomes associated with ventilator-associated pneumonia (VAP) in a European pediatric intensive care unit (PICU). METHODS: A total of 451 children who had been mechanically ventilated in the PICU for >= 48 hours during a 3-year period were enrolled in this prospective study. RESULTS: In comparison with children without VAP, 30 children (6.6%) who developed VAP had a longer PICU stay (P=0.0001) and hospital stay (P=0.0001), and a higher mortality rate (P=0.04). Logistic regression analysis showed that the need for re-intubation (P=0.0001), the presence of tracheostomy (P=0.04), and enteral feeding (P=0.02) were independent risk factors for VAP. CONCLUSIONS: A relevant proportion of intubated children develop VAP, which is closely related to invasive procedures. As VAP is associated with increased medical costs and death, multicenter studies are urgently needed to improve the therapeutic approach to VAP and VAP prevention. PMID- 24235071 TI - Active rehabilitation with venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation in a pediatric patient. AB - BACKGROUND: Active physical rehabilitation while bridged to lung transplantation with venovenous (VV) extracorporeal membrane oxygenation (ECMO) is an evolving treatment option in adults with limited published experience in pediatric patients. METHODS: The administration of VV ECMO through the placement of a single-site bicaval dual-lumen (BCDL) catheter (Avalon Laboratories, Rancho Dominguez, CA, USA) permits respiratory support in a critically ill patient with avoidance of sedation and paralytics while allowing rehabilitation and oral nutrition. RESULTS: A 13-year-old girl with advanced interstitial lung disease underwent active rehabilitation while being bridged to lung transplantation with single-site VV ECMO. CONCLUSIONS: The innovative use of single-site VV ECMO with a BCDL catheter is transforming the care of adult patients with advanced lung disease and acute respiratory failure as a method to extend the life of a lung transplantation candidate to maximize all opportunities for organ availability. Based on our experiences, clinicians caring for children should be aware of this potential option in pediatric patients requiring lung transplantation. PMID- 24235072 TI - Progression of left ventricular diastolic dysfunction in ethnic minorities. AB - BACKGROUND: Approximately 50 % of heart failure cases are due to diastolic failure. Generally, it is thought that asymptomatic diastolic dysfunction precedes the development of diastolic heart failure, representing an ideal time for intervention. Previous studies have examined progression rates in non minority populations only. OBJECTIVE: To determine the rate of diastolic dysfunction progression and the associated risk factors in a predominately ethnic minority population. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of participants drawn from the echocardiogram database and Electronic Health Record (EHR) for an academic medical center. Individuals with 2 or more echocardiograms showing diastolic dysfunction during a six year study period (2006-2012) were selected. MAIN OUTCOME MEASURES: Change in diastolic function grade over time and risk factors associated with this change. RESULTS: During the six-year retrospective study period, 154 patients with 2 or more echocardiograms demonstrating diastolic dysfunction were reviewed; these represented 496 echocardiograms. The mean time between echocardiograms was 1.9 years. Mean age was 64.6 (+/-10.1) years,81 % were female, and average BMI was 30.5(+/-7.4). The majority of subjects had Grade I diastolic dysfunction at the initial examination (87.7 % (n = 135)); 9 % (n = 14) had Grade II, and 3 % (n = 5) had Grade III. Approximately 27.9 % (n = 43) of the study cohort demonstrated overall worsening grade of diastolic dysfunction over time. Diastolic dysfunction grade was unchanged in 62 %(n = 96), improved in 9.7 % (n = 14), and worsened then improved in 0.7 % (n = 1). CONCLUSIONS: Our study showed a slightly higher rate of diastolic dysfunction progression in this predominately ethnic minority population. This is consistent with a previous study in a non-minority population demonstrating the progressive nature of diastolic dysfunction over time.Understanding the role of cardiovascular disease risk factors in accelerating progression rates from asymptomatic diastolic dysfunction to symptomatic stages is paramount to optimize intervention strategies. PMID- 24235073 TI - High-efficiency on-line haemodiafiltration improves conduit artery endothelial function compared with high-flux haemodialysis in end-stage renal disease patients. AB - BACKGROUND: Middle molecular weight uraemic toxins are considered to play an important role in vascular dysfunction and cardiovascular outcomes in end-stage renal disease (ESRD) patients. Recent dialysis techniques based on convection, specifically high-efficiency on-line haemodiafiltration (HDF), enhance the removal of middle molecular weight toxins and reduce all-cause mortality in haemodialysis (HD) patients. However, the mechanisms of these improved outcomes remain to be established. METHODS: This prospective study randomly assigned 42 ESRD patients to switch from high-flux HD to high-efficiency on-line HDF (n=22) or to continue HD (n=20). Brachial artery endothelium-dependent flow-mediated dilatation, central pulse pressure, carotid artery intima-media thickness (IMT), internal diastolic diameter and distensibility and circulating markers of uraemia, inflammation and oxidative stress were blindly assessed before and after a 4-month follow-up. RESULTS: Brachial flow-mediated dilatation and carotid artery distensibility increased significantly in the HDF group compared with HD, while carotid IMT and diameter remained similar. HDF decreased predialysis levels of the uraemic toxins beta2-microglobulin, phosphate and blood TNFalpha mRNA expression. Oxidative stress markers were not different between the HD and HDF groups. Blood mRNA expression of protein kinase C beta2, an endothelial NO synthase (eNOS) inhibitor, decreased significantly with HDF. CONCLUSIONS: High efficiency on-line HDF prevents the endothelial dysfunction and stiffening of the conduit arteries in ESRD patients compared with high-flux HD. HDF decreases uraemic toxins, vascular inflammation, and is associated with subsequent improvement in eNOS functionality. These results suggest that reduced endothelial dysfunction may be an intermediate mechanism explaining the beneficial outcomes associated with HDF. PMID- 24235074 TI - Differential scaling of glomerular filtration rate and ingested metabolic burden: implications for gender differences in chronic kidney disease outcomes. AB - BACKGROUND: Men commence dialysis with a higher estimated glomerular filtration rate (eGFR) than women and are more likely to transition from chronic kidney disease (CKD) to end-stage renal disease. We hypothesized that for a given estimated body surface area (BSA) men have a greater metabolic burden, and that consequently, the practice of indexing GFR to BSA results in gender differences in the degree of biochemical uraemia. METHODS: Metabolic burden was assessed as estimated dietary protein, calorie, phosphorus, sodium and potassium intakes and urinary urea nitrogen excretion in the Chronic Renal Insufficiency Cohort, Modification of Diet in Renal Disease study, and National Health and Nutrition Examinations Surveys (NHANES) 1999-2010. Uraemia was characterized by serum biochemistry. RESULTS: Per m(2) BSA, men had greater urea nitrogen excretion and intakes of all dietary parameters (P < 0.001 for all). For a given BSA-indexed iothalamate GFR or eGFR, male gender was associated with a 10-15% greater serum urea nitrogen (P < 0.001), giving men with a BSA-indexed GFR of 70-75 mL/min/1.73 m(2) the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m(2). However, indexing metabolic burden and GFR to alternative body size measures (estimated total body water, lean body mass or resting energy expenditure) abolished/reversed the gender associations. In NHANES, BSA-indexed eGFR distribution was very similar for men and women, so that adjusting for eGFR had little effect on the gender difference in serum urea. CONCLUSIONS: Indexing GFR to BSA across genders may approximate nature's indexing approach, but gives men a greater ingested burden of protein, calories, sodium, phosphorus and potassium per mL/min GFR. This has implications for gender differences in CKD outcomes. PMID- 24235075 TI - Health status as a potential mediator of the association between hemodialysis vascular access and mortality. AB - BACKGROUND: It is unknown whether the selection of healthier patients for arteriovenous fistula (AVF) placement explains higher observed catheter associated mortality among elderly hemodialysis patients. METHODS: From the United States Renal Data System 2005-2007, we used proportional hazard models to examine 117 277 incident hemodialysis patients aged 67-90 years for the association of initial vascular access type and 5-year mortality after accounting for health status. Health status was defined as functional status at dialysis initiation and number of hospital days within 2 years prior to dialysis initiation. RESULTS: Patients with catheter alone had more limited functional status (25.5 versus 10.8% of those with AVF) and 3-fold more prior hospital days than those with AVF (mean 18.0 versus 5.4). In the unadjusted model, the likelihood of death was higher for arteriovenous grafts (AVG) {Hazard ratio (HR) 1.20 [95% CI (1.16-1.25)], catheter plus AVF [HR 1.34 (1.31-1.38)], catheter plus AVG [HR 1.46 (1.40-1.52)] and catheter only [HR 1.95 (1.90-1.99)]}, compared with AVF (P < 0.001). The association attenuated -23.7% (95% CI -22.0, -25.5) overall (AVF versus all other access types) after adjusting for the usual covariates (including sociodemographics, comorbidities and pre-dialysis nephrology care) {AVG [HR 1.21 (1.17-1.26)], catheter plus AVF [HR 1.27 (1.24-1.30)], catheter plus AVG [HR 1.38 (1.32-1.43)] and catheter only [HR 1.69 (1.66-1.73)], P < 0.001}. Additional adjustment for health status further attenuated the association by another -19.7% (-18.2, -21.3) overall but remained statistically significant . CONCLUSIONS: The observed attenuation in mortality differences previously attributed to access type alone suggests the existence of selection bias. Nevertheless, the persistence of an apparent survival advantage after adjustment for health status suggests that AVF should still be the access of choice for elderly individuals beginning hemodialysis until more definitive data eliminating selection bias become available. PMID- 24235076 TI - Children of non-Western origin with end-stage renal disease in the Netherlands, Belgium and a part of Germany have impaired health-related quality of life compared with Western children. AB - BACKGROUND: Many children with end-stage renal disease (ESRD) living in Western Europe are of non-Western European origin. They have unfavourable somatic outcomes compared with ESRD children of Western origin. In this study, we compared the Health-related Quality of Life (HRQoL) of both groups. METHODS: All children (5-18 years) with ESRD included in the RICH-Q project (Renal Insufficiency therapy in Children-Quality assessment and improvement) or their parents were asked to complete the generic version of the Paediatric Quality-of Life Inventory 4.0 (PedsQL). RICH-Q comprises the Netherlands, Belgium and a part of Germany. Children were considered to be of non-Western origin if they or at least one parent was born outside Western-European countries. Impaired HRQoL for children with ESRD of Western or non-Western origin was defined as a PedsQL score less than fifth percentile for healthy Dutch children of Western or non-Western origin, respectively. RESULTS: Of the 259 eligible children, 230 agreed to participate. One hundred and seventy-four children responded (response rate 67%) and 55 (32%) were of non-Western origin. Overall, 31 (56%) of the ESRD children of non-Western origin, and 58 (49%) of Western origin had an impaired total HRQoL score. Total HRQoL scores of children with ESRD of Western origin and non-Western origin were comparable, but scores on emotional functioning and school functioning were lower in non-Western origin (P=0.004 and 0.01, respectively). The adjusted odds ratios (95% confidence interval) for ESRD children of non Western origin to have impaired emotional functioning and school functioning, compared with Western origin, were 3.3(1.5-7.1) and 2.2(1.1-4.2), respectively. CONCLUSION: Children with ESRD of non-Western origin in three Western countries were found to be at risk for impaired HRQoL on emotional and school functioning. These children warrant special attention. PMID- 24235077 TI - Novel insights from genetic and epigenetic studies in understanding the complex uraemic phenotype. AB - Like in many other common complex disorders, studies of chronic kidney disease (CKD) can now make use of the increasing knowledge of the human genome, its variations and impact on disease susceptibility, initiation, progression and complications. Such studies are facilitated by novel readily available high through-put genotyping methods and sophisticated analytical approaches to scan the genome for DNA variations and epigenetic modifications. Here, we review some of the recent discoveries that have emerged from these studies and expanded our knowledge of genetic risk loci and epigenetic markers in CKD pathophysiology. Obstacles and practical issues in this field are discussed. PMID- 24235078 TI - Treatment of renal sarcoidosis: is there a guideline? Overview of the different treatment options. AB - Sarcoidosis is a multisystem granulomatous disease of unknown aetiology characterized by the presence of noncaseating granulomas. It may affect any organ including the kidney. A disordered calcium metabolism is most often responsible for the development of renal failure. Granulomatous interstitial nephritis is the most typical histological finding, but it rarely leads to renal insufficiency. Since development of renal insufficiency in sarcoidosis is uncommon, we lack large (randomized) trials concerning the treatment of this disorder. We gather most information from case reports and small series. Our knowledge of pulmonary sarcoidosis is more comprehensive. It is, however, impossible to treat renal manifestations identically because some of the drugs used in pulmonary sarcoidosis are nephrotoxic. Moreover, renal sarcoidosis is a specific entity with its own characteristics and response to therapy. A guideline for treatment is currently missing. Based on a review of the literature, we present an overview of the different treatment options to promote a more uniform and scrutinized approach of this disease. Hypercalcaemia and hypercalciuria can be treated with corticosteroids, (hydroxy)chloroquine or ketoconazole. Preventive measures play a supportive role. In granulomatous interstitial nephritis, glucocorticoids are the standard of care. In patients with failure of or a contraindication to corticosteroids or in those patients who need a high maintenance dose of corticosteroids, azathioprine or mycophenolate mofetil can be used. TNF-alpha inhibitors are useful in case of steroid-resistant sarcoidosis or in patients who develop severe steroid toxicity. With increasing insight in the pathogenesis of sarcoidosis, other immunosuppressive drugs have been proposed, but more research is necessary before their routine use can be advocated. PMID- 24235079 TI - A ray of light in the dark: alternative approaches to the assessment and treatment of ischemic nephropathy. PMID- 24235080 TI - Healthcare systems and chronic kidney disease: putting the patient in control. AB - Today, health policy seems to be on the top of governments' agendas around the world. Healthcare systems are challenged by a number of phenomena happening on a global scale; these trends include demographic change in terms of an ageing population, an increase in chronic disease, patients having higher expectations on healthcare delivery and above all a major pressure on public finances to slow increasing healthcare expenditures. Such developments are forcing policy-makers to reform healthcare systems. First, there is a tendency towards decentralization of responsibilities. Second, governments are moving towards reimbursement schemes rewarding good outcomes and performance. Third, great importance is being attributed to transparency and accountability, and to introduce competition in healthcare. Fourth, attention is being shifted from simple treatment of a disease towards preventive initiatives, in a more holistic approach to health. Finally, healthcare policy-makers are recognizing the importance of empowering patients to give them control over decisions regarding their own health. These dynamics can be observed in chronic kidney disease, the management of which is a huge economic burden to healthcare systems globally, and which represents a good example of a field where important changes can be witnessed in therapy, technology, delivery and financing. PMID- 24235081 TI - Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. AB - CONTEXT: Velcalcetide, also known as AMG 416, is a novel, long-acting selective peptide agonist of the calcium sensing receptor. It is being developed as an intravenous treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients with chronic kidney disease-mineral and bone disorder. OBJECTIVE: To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of velcalcetide in healthy male volunteers. METHODS: The study was a double-blind, randomized, placebo-controlled, single-dose, dose-escalation study in healthy males aged 18-45 years conducted at a single center. Each cohort included eight subjects randomized 6:2 to velcalcetide or placebo. INTERVENTION: Velcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously. OUTCOMES: Measurements included plasma ionized calcium (iCa), serum total calcium, intact parathyroid hormone (iPTH), phosphorus and fibroblast growth factor-23 (FGF23), 1,25-dihydroxyvitamin D, calcitonin and urine creatinine, calcium and phosphorus and plasma pharmacokinetics for velcalcetide. Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study. RESULTS: Intravenous administration of velcalcetide was well tolerated with no adverse reaction of nausea, vomiting or diarrhea reported. Velcalcetide mediated dose-dependent decreases in serum iPTH at 30 min, FGF23 at 24 h and iCa at 12 h post dose (P<0.05) and in urine fractional excretion of phosphorus and increases in tubular reabsorption of phosphorus. Velcalcetide plasma exposure increased in a dose-related manner and the terminal elimination of half-life was comparable across the dose range evaluated and ranged from 18.4 to 20.0 h. CONCLUSION: Single IV doses of velcalcetide were well tolerated and associated with rapid, sustained, dose-dependent reductions in serum PTH. The results support further evaluation of velcalcetide as a treatment for SHPT in hemodialysis patients. PMID- 24235082 TI - The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease. AB - BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD. METHODS: The study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach. RESULTS: DNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-alpha stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = 0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid. CONCLUSIONS: Since an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions. PMID- 24235083 TI - Chronic hypercalcaemia from inactivating mutations of vitamin D 24-hydroxylase (CYP24A1): implications for mineral metabolism changes in chronic renal failure. AB - BACKGROUND: Loss-of-function mutations of vitamin D-24 hydroxylase have recently been recognized as a cause of hypercalcaemia and nephrocalcinosis/nephrolithiasis in infants and adults. True prevalence and natural history of this condition are still to be defined. METHODS: We describe two adult patients with homozygous mutations and six related heterozygous carriers. Mineral and hormonal data in these patients were compared with that in 27 patients with stage 2-3 chronic kidney disease and 39 healthy adult kidney donors. RESULTS: Probands had recurrent nephrolithiasis, chronic hypercalcaemia with depressed parathyroid hormone (PTH) and increased 1,25(OH)(2)D levels; carriers had nephrolithiasis (two of six), hypercalciuria (two of six) and high or normal-high 1,25(OH)(2)D (four of four). Corticosteroids did not reduce plasma and urine calcium levels, but ketoconazole did, indicating that 1,25(OH)(2)D production is not maximally depressed despite coexisting hypercalcaemia, high 1,25(OH)(2)D and depressed PTH, and that 1,25(OH)(2)D degradation through vitamin D-24 hydroxylase is a regulator of plasma 1,25(OH)(2)D levels. Both probands had vascular calcifications and high bone mineral content. One developed stage 3b renal failure: in this patient 1,25(OH)(2)D decreased within normal limits as glomerular filtration rate (GFR) fell and PTH rose to high-normal values, yet hypercalcaemia persisted and the ratio of 1,25(OH)(2)D to GFR remained higher than normal for any degree of GFR. CONCLUSIONS: This natural model indicates that vitamin D-24 hydroxylase is a key physiologic regulator of calcitriol and plasma calcium levels, and that balanced reduction of 1,25(OH)(2)D and GFR is instrumental for the maintenance of physiologic calcium levels and balance in chronic kidney diseases. PMID- 24235085 TI - Protein A immunoadsorption cannot significantly remove the soluble receptor of urokinase from sera of patients with recurrent focal segmental glomerulosclerosis. AB - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a serious disease, the pathogenesis of which is unknown. Its recurrence after transplantation (Tx) and its partial remission after treatment with immunoadsorption (IA) on a protein A column indicate the existence of a circulating factor responsible for the disease that is able to bind to a protein A column. Recently, the soluble receptor of urokinase (suPAR) was described as the factor responsible for FSGS. We tested the capacity of suPAR to bind to protein A and to be eliminated by IA. METHODS: We measured suPAR in eluates of protein A columns from seven patients with recurrent FSGS after Tx (rFSGS) treated with IA, and in the serum of 13 patients with rFSGS and 11 healthy donors (HDs). Additionally, the plasma of these patients was immunoadsorbed in vitro on a protein A Sepharose column, and we quantified suPAR in the eluates and in pre- and post-column samples. RESULTS: The concentration of suPAR was higher in the plasma of patients with rFSGS than that of HD patients. However, the concentration of suPAR was similar before and after IA on protein A for the rFSGS and HD samples. The suPAR concentration was very low in the eluates from protein A columns incubated with plasma from HD or rFSGS patients. However, 85% of rFSGS patients showed a decrease in immunoglobulin G and proteinuria. CONCLUSIONS: Thus, suPAR does not significantly bind to protein A in vitro or in vivo. PMID- 24235086 TI - Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients. AB - BACKGROUND: Although it has been shown that a vagus nerve stimulation of brain dead (BD) donors leads to an improvement of renal function in recipients in an acute allograft rejection model, its influence on chronic allograft nephropathy is still unknown. In the present study, we assessed the influence of donor vagus nerve stimulation on survival, renal function and histology in a chronic allograft model. METHODS: Brain death was induced in Fisher rats, and electro stimulation of the vagus nerve was applied in one group (BD + vagus) during the whole course of BD (6 h). Unstimulated BD Fisher donor rats served as controls. Allogeneic Lewis rats were used as recipients and no immunosuppressive medication was administered. Blood and urine samples were collected every second week. Banff classification was assessed from harvested allografts. RESULTS: Vagal stimulation of BD donors resulted in an improved survival of recipients. Long-term renal function was significantly better in these recipients as reflected by improved creatinine clearance. Banff classification revealed significantly reduced vasculopathy and less tubulopathy in the BD + vagus group. CONCLUSIONS: In conclusion, our data demonstrate a long-lasting beneficial effect of vagus nerve stimulation in BD donors on the renal transplantation outcome. Hence, activation of the cholinergic anti-inflammatory pathway in BD donors may represent a novel therapeutic modality to reduce chronic allograft nephropathy without any side effects for the recipient. PMID- 24235084 TI - The iron cycle in chronic kidney disease (CKD): from genetics and experimental models to CKD patients. AB - Iron is essential for most living organisms but iron excess can be toxic. Cellular and systemic iron balance is therefore tightly controlled. Iron homeostasis is dysregulated in chronic kidney disease (CKD) and contributes to the anemia that is prevalent in this patient population. Iron supplementation is one cornerstone of anemia management in CKD patients, but has not been rigorously studied in large prospective randomized controlled trials. This review highlights important advances from genetic studies and animal models that have provided key insights into the molecular mechanisms governing iron homeostasis and its disturbance in CKD, and summarizes how these findings may yield advances in the care of this patient population. PMID- 24235087 TI - The dyadic interaction of relationships and disability type on informal carer subjective well-being. AB - PURPOSE: Care-related factors have frequently been associated with elevated levels of distress and diminished subjective well-being. However, these variables have traditionally been considered independently. The objectives of this study were to explore the subjective well-being of informal carers in Australia and to specifically examine the effect of the dyadic interaction between the caring relationship and type of disability on the subjective well-being of informal carers. METHODS: Informal carers (n = 4,096) completed the Personal Wellbeing Index (PWI) and Depression and Stress Scales. Analysis of covariance was used to compare the subjective well-being of carers to the general population while controlling for socio-demographic factors. To examine the dyadic relationship, a multivariate analysis of covariance was employed. RESULTS: After socio demographic variables were controlled, informal carers reported significantly lower PWI scores compared to the general population. The results of the multivariate analysis of covariance revealed a significant interaction between the caring relationship and the type of disability being managed on subjective well-being. No differences were found for symptoms of depression and stress. CONCLUSIONS: The findings of this study imply that the detrimental effect of caring on subjective well-being is magnified for carers who support a child with a mental illness or multiple types of disabilities. These carers displayed the lowest levels of subjective well-being, highlighting the dyadic effects of care related variables. Consideration of these factors is essential to target effective intervention programs for those most at risk of diminished well-being. PMID- 24235088 TI - Revisiting formulation: part 1. The tasks of formulation: their rationale and philosophic basis. AB - OBJECTIVE: This paper notes the continuing problems that Royal Australian and New Zealand College of Psychiatry (RANZCP) candidates and other professionals have with the task of formulation. It re-establishes this as a problematic to be understood and reviews its intellectual history, its rationale, the tools of reasoning that it requires and the nature of the challenges that it can pose to individuals. Its premise is that an understanding of the theoretical basis of formulation is required prior to application of pedagogical tools in teaching and remediation. Four tasks of formulation implied in the definition provided in the RANZCP Formulation Guidelines for Candidates are identified, and their rationale and theoretical status reviewed. CONCLUSION: Task 1, classification, must address both diagnoses and problems. Task 2, using theory to infer meaning, ideally requires multiple models and theories in development of a set of hypotheses, using inductive inference (plausibility). Task 3, prioritising hypotheses, requires abduction, defined as inference to the best explanation. Task 4, integrating hypotheses, may aim for reconciling systems (syncretism), but is likely to use the more problematic eclecticism. The task of formulation is thus challenging but well prescribed by philosophers for thousands of years. PMID- 24235089 TI - Revisiting formulation: part 2. The task of addressing the concept of the unique individual. Remediating problems with formulation. AB - OBJECTIVE: The purpose of this paper is to review the theoretical basis of addressing the concept of the unique individual, one of the tasks prescribed in the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Formulation guidelines for candidates, and to propose a rational basis for remediation of the problems that many candidates and other professionals have with formulation. CONCLUSION: The difficulty that RANZCP candidates and other mental health professionals have in producing a completely integrated account of an individual is multi-determined, but is partly explainable on theoretical grounds. Understanding why this task (and other tasks of formulation) is problematic requires knowledge of its intellectual history, its rationale, the tools of reasoning that it requires and the nature of the challenges that it can pose to individuals. The paper argues that a rational plan for remediation of a professional's problems with formulation requires first a 'formulation' of those problems, drawing on the theories discussed and acknowledging the uniqueness of that individual. In answering the question, 'Why is this person having difficulty formulating this patient at this time?', one needs to address cultural, social and systemic factors, and psychological factors such as the degree of psychological mindedness of the person seeking remediation. Hypotheses based on the formulation about the professional's difficulty should be developed and tested by interventions. PMID- 24235090 TI - "We now control our evolution": circumventing ethical and logical cul-de-sacs of an anticipated engineering revolution. AB - Philosophers, scientists, and other researchers have increasingly characterized humanity as having reached an epistemic and technical stage at which "we can control our own evolution." Moral-philosophical analysis of this outlook reveals some problems, beginning with the vagueness of "we." At least four glosses on "we" in the proposition "we, humanity, control our evolution" can be made: "we" is the bundle of all living humans, a leader guiding the combined species, each individual acting severally, or some mixture of these three involving a market interpretation of future evolutionary processes. While all of these glosses have difficulties under philosophical analysis, how we as a species handle our fate via technical developments is all-important. I propose our role herein should be understood as other than controllers of our evolution. PMID- 24235091 TI - Loneliness mediates the relationship between emotion dysregulation and bulimia nervosa/binge eating disorder psychopathology in a clinical sample. AB - Emotion dysregulation has been linked to binge eating disorder (BED) and bulimia nervosa (BN) although the mechanisms by which it affects BN/BED psychopathology are unclear. This study tested loneliness as a mediator between emotion dysregulation and BN/BED psychopathology. A treatment-seeking sample of 107 women with BN or BED was assessed for loneliness (UCLA Loneliness Scale), emotion dysregulation (Difficulties in Emotion Regulation Scale), and BN/BED psychopathology (Eating Disorder Examination) before treatment. Hierarchical linear regressions and bootstrapping mediation models were run. Greater overall emotion dysregulation was associated with greater BN/BED psychopathology, mediated by loneliness (95 % CI 0.03, 0.09). Emotion dysregulation, however, did not mediate between loneliness and BN/BED psychopathology (95 % CI -0.01, 0.01). Targeting loneliness may effectively treat emotional aspects of BN/BED in women. PMID- 24235092 TI - The impact of meal consumption on emotion among individuals with eating disorders. AB - PURPOSE: This pilot study sought to determine how meal consumption impacts affective states for treatment-seeking individuals with eating disorders (ED). METHODS: Participants with heterogeneous ED diagnoses completed the State-Trait Anxiety Inventory, Positive and Negative Affect Schedule, and Profile of Mood States measures before and immediately after meal consumption. RESULTS: Meal consumption was associated with significant decreases in negative affect and total mood disturbance for individuals with binge eating disorder (BED). Decreases in negative affect across meal time for individuals with BED were significantly different from increases in negative affect for participants with anorexia nervosa (AN) and bulimia nervosa (BN). CONCLUSION: Findings indicate that individuals with BED have significantly different affective responses to eating non-binge meals than individuals with AN or BN. Data suggest changes in negative affect following meal consumption may be specific to certain ED diagnoses. Results provide preliminary evidence consistent with the idea that emotion states may function as maintenance mechanisms for psychopathology among ED diagnoses. Limitations and future directions pertaining to food-mood relationships for individuals with ED are discussed. PMID- 24235093 TI - A novel functional class 2 integron in clinical Proteus mirabilis isolates. AB - OBJECTIVES: To describe a novel functional class 2 integron that was found in clinical Proteus mirabilis isolates. METHODS: Class 1 and 2 integrons were screened by PCR in 153 clinical Proteus isolates. The variable regions of class 1 and 2 integrons were determined by restriction analysis and sequencing. The mutations of internal stop codons in class 2 integrons and their common promoters were also determined by sequencing. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used to analyse the phylogenetic relations of class 2 integron-positive P. mirabilis isolates. RESULTS: Class 1 integrons were detected in 96 (63%) of 153 Proteus isolates: eight different gene cassette arrays were detected, including dfrA32-ereA1-aadA2, which was detected for the first time in P. mirabilis. Class 2 integrons were detected in 101 (66%) of 153 Proteus isolates: four different gene cassette arrays were detected, including dfrA1 catB2-sat2-aadA1, which was detected for the first time in a class 2 integron. A novel functional class 2 integron was detected in 38 P. mirabilis isolates with a common promoter (-35 TTTAAT|16 bp|-10 TAAAGT). The variable region of this functional class 2 integron contained dfrA14 and three novel open reading frames with unknown functions. Very similar ERIC-PCR fingerprinting patterns were detected in these 38 P. mirabilis isolates and were different from other class 2 integron-positive isolates. CONCLUSIONS: A novel functional class 2 integron was found for the first time in P. mirabilis. These functional class 2 integron harbouring P. mirabilis isolates were likely to be clonally spread in our hospital. PMID- 24235094 TI - A kinetic analysis of the inhibition of FOX-4 beta-lactamase, a plasmid-mediated AmpC cephalosporinase, by monocyclic beta-lactams and carbapenems. AB - OBJECTIVES: Class C beta-lactamases are prevalent among Enterobacteriaceae; however, these enzymes are resistant to inactivation by commercially available beta-lactamase inhibitors. In order to find novel scaffolds to inhibit class C beta-lactamases, the comparative efficacy of monocyclic beta-lactam antibiotics (aztreonam and the siderophore monosulfactam BAL30072), the bridged monobactam beta-lactamase inhibitor BAL29880, and carbapenems (imipenem, meropenem, doripenem and ertapenem) were tested in kinetic assays against FOX-4, a plasmid mediated class C beta-lactamase (pmAmpC). METHODS: The FOX-4 beta-lactamase was purified. Steady-state kinetics, electrospray ionization mass spectrometry (ESI MS) and ultraviolet difference (UVD) spectroscopy were conducted using the beta lactam scaffolds described. RESULTS: The K(i) values for the monocyclic beta lactams against FOX-4 beta-lactamase were 0.04 +/- 0.01 MUM (aztreonam) and 0.66 +/- 0.03 MUM (BAL30072), and the Ki value for the bridged monobactam BAL29880 was 8.9 +/- 0.5 MUM. For carbapenems, the Ki values ranged from 0.27 +/- 0.05 MUM (ertapenem) to 2.3 +/- 0.3 MUM (imipenem). ESI-MS demonstrated the formation of stable covalent adducts when the monocyclic beta-lactams and carbapenems were reacted with FOX-4 beta-lactamase. UVD spectroscopy suggested the appearance of different chromophoric intermediates. CONCLUSIONS: Monocyclic beta-lactam and carbapenem antibiotics are effective mechanism-based inhibitors of FOX-4 beta lactamase, a clinically important pmAmpC, and provide stimulus for the development of new inhibitors to inactivate plasmidic and chromosomal class C beta-lactamases. PMID- 24235096 TI - A GC1 Acinetobacter baumannii isolate carrying AbaR3 and the aminoglycoside resistance transposon TnaphA6 in a conjugative plasmid. AB - OBJECTIVES: To locate the acquired antibiotic resistance genes, including the amikacin resistance transposon TnaphA6, in the genome of an Australian isolate belonging to Acinetobacter baumannii global clone 1 (GC1). METHODS: A multiply antibiotic-resistant GC1 isolate harbouring TnaphA6 was sequenced using Illumina HiSeq, and reads were used to generate a de novo assembly and determine multilocus sequence types (STs). PCR was used to assemble the AbaR chromosomal resistance island and a large plasmid carrying TnaphA6. Plasmid DNA sequences were compared with ones available in GenBank. Conjugation experiments were conducted. RESULTS: The A. baumannii GC1 isolate G7 was shown to include the AbaR3 antibiotic resistance island. It also contains an 8.7 kb cryptic plasmid, pAb-G7-1, and a 70,100 bp plasmid, pAb-G7-2, carrying TnaphA6. pAb-G7-2 belongs to the Aci6 Acinetobacter plasmid family. It encodes transfer functions and was shown to conjugate. Plasmids related to pAb-G7-2 were detected in further amikacin-resistant GC1 isolates using PCR. From the genome sequence, isolate G7 was ST1 (Institut Pasteur scheme) and ST231 (Oxford scheme). Using Oxford scheme PCR-based methods, the isolate was ST109 and this difference was traced to a single base difference resulting from the inclusion of the original primers in the gpi segment analysed. CONCLUSIONS: The multiply antibiotic-resistant GC1 isolate G7 carries most of its resistance genes in AbaR3 located in the chromosome. However, TnaphA6 is on a conjugative plasmid, pAb-G7-2. Primers developed to locate TnaphA6 in pAb-G7-2 will simplify the detection of plasmids related to pAb-G7-2 in A. baumannii isolates. PMID- 24235095 TI - Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs. AB - OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter. PMID- 24235097 TI - Evaluation of cerebral arteriovenous malformation using 'dual vessel fusion' technology. AB - AIM: This study explored the value of using a vessel fusion technique for visualizing and evaluating the vessel structure of patients diagnosed with arteriovenous malformations (AVMs). MATERIALS AND: methods 10 patients with AVMs supplied by multiple cerebral arteries were investigated. The three-dimensional structure of the AVM nidus, feeding arteries, and draining veins were reconstructed from rotational angiographic images and then displayed on a single image in a fused manner. RESULTS: In the vessel fusion image, the tangled cluster of vessels surrounding the AVMs could be clearly visualized in three-dimensional space from a selected optimal viewing angle. Each AVM nidus component with its specific feeding arteries and venous drainage could be accurately identified. CONCLUSIONS: The vessel fusion technique offered detailed anatomical information that enabled clinicians to better understand the AVM structure, which helped with treatment planning. PMID- 24235098 TI - Exploring the efficacy of cyclic vs static aspiration in a cerebral thrombectomy model: an initial proof of concept study. AB - BACKGROUND AND PURPOSE: Current technology for endovascular thrombectomy in ischemic stroke utilizes static loading and is successful in approximately 85% of cases. Existing technology uses either static suction (applied via a continuous pump or syringe) or flow arrest with a proximal balloon. In this paper we evaluate the potential of cyclic loading in aspiration thrombectomy. METHODS: In order to evaluate the efficacy of cyclic aspiration, a model was created using a Penumbra aspiration system, three-way valve and Penumbra 5Max catheter. Synthetic clots were aspirated at different frequencies and using different aspiration mediums. Success or failure of clot removal and time were recorded. All statistical analyses were based on either a one-way or two-way analysis of variance, Holm-Sidak pairwise multiple comparison procedure (alpha=0.05). RESULTS: Cyclic aspiration outperformed static aspiration in overall clot removal and removal speed (p<0.001). Within cyclic aspiration, Max Hz frequencies (~6.3 Hz) cleared clots faster than 1 Hz (p<0.001) and 2 Hz (p=0.024). Loading cycle dynamics (specific pressure waveforms) affected speed and overall clearance (p<0.001). Water as the aspiration medium was more effective at clearing clots than air (p=0.019). CONCLUSIONS: Cyclic aspiration significantly outperformed static aspiration in speed and overall clearance of synthetic clots in our experimental model. Within cyclic aspiration, efficacy is improved by increasing cycle frequency, utilizing specific pressure cycle waveforms and using water rather than air as the aspiration medium. These findings provide a starting point for altering existing thrombectomy technology or perhaps the development of new technologies with higher recanalization rates. PMID- 24235099 TI - Percutaneous sclerotherapy with ethanolamine oleate for venous malformations of the head and neck. AB - INTRODUCTION: Venous malformations frequently occur in the head and neck, and they can require treatment for a variety of reasons. Among multiple therapeutic approaches employed, percutaneous sclerotherapy has become one of the most commonly used treatments, with numerous sclerosants successfully utilized. Ethanolamine oleate has approval from the Food and Drug Administration for sclerosis of esophageal varices, and is used by some practitioners for the treatment of venous malformations. This study reports single center results of percutaneous sclerotherapy with ethanolamine oleate to treat venous malformations of the head and neck. MATERIALS AND METHODS: Prospectively maintained procedural records were retrospectively reviewed to identify all patients with venous malformations who underwent percutaneous sclerotherapy. The Mulliken and Glowacki classification was used to diagnose venous malformations. Medical records and images were reviewed to record demographic information, lesion characteristics, treatment sessions, and clinical and imaging response. Quantitative volumetric analysis was conducted to augment commonly used poorly reproducible subjective outcome measures. Response was assessed after each session and completion of all percutaneous treatment. A chi(2) analysis was performed to evaluate the effects of the above described characteristics on outcomes. RESULTS: 52 interventions were performed for lesions in 26 patients. No complications occurred following any procedures. Response to individual sessions was categorized as excellent following two (3.8%) sessions, good following 45 (86.5%), and fair following four (7.7%) session. No sessions resulted in poor responses. Final results were excellent in two patients (7.7%), good in 22 (84.6%), and fair in two (7.7%). Average lesion volume reduction was 39% following each session, and 61% after treatment completion. Periorbital lesions were significantly less likely than lesions located elsewhere to have good or excellent outcomes. No other lesion or demographic features affected outcomes. CONCLUSIONS: Percutaneous sclerotherapy with ethanolamine oleate appears to be safe and effective for the treatment of venous malformations and should be considered when treating these complex lesions. The efficacy of this agent appears to match or exceed that of other sclerosants used for such treatment, and further investigation in prospective controlled research is warranted. PMID- 24235100 TI - Digital model planning and computerized fabrication of orthognathic surgery wafers. AB - Conventional orthognathic wafers are made by a process involving manual movement of stone dental models and acrylic laboratory fabrication. In addition, a facebow record and semi-adjustable articulator system are required for maxillary osteotomy cases. This paper introduces a novel process of producing both intermediate and final orthognathic surgical wafers using a combination of computerized digital model simulation and three-dimensional print fabrication, without the need for either a facebow record or the additional ionizing radiation exposure associated with cone beam computerized tomography. PMID- 24235101 TI - The effect of puberty on fat oxidation rates during exercise in overweight and normal-weight girls. AB - Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre early pubertal girls had higher max FOR [6.9 +/- 1.4 mg.kg fat free mass (FFM)( 1).min(-1)] than NW mid-late pubertal girls (2.2 +/- 0.9 mg.kg FFM(-1).min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 +/- 2.1 mg.kg FFM(-1).min(-1)), and OW mid-late pubertal girls (3.3 +/- 0.9 mg.kg FFM(-1).min(-1)) (P < 0.05). Bivariable analyses showed positive associations between FOR with homeostatic model assessment of IR (P = 0.001), leptin (P < 0.001), and leptin-to-adiponectin ratio (P = 0.001), independent of percent body fat. Max FOR decreased in NW girls during mid-late puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls. PMID- 24235102 TI - Determinants of resting lipid oxidation in response to a prior bout of endurance exercise. AB - A single bout of exercise can alter subsequent resting metabolism for many hours and into the next day. However, differences between men and women, effects of nutritional state, and relative effects of resting metabolic rate (RMR) and respiratory exchange ratio (RER) in controlling the increase in lipid oxidation (Lox) after exercise are not yet clear. Effects of aerobic capacity (Vo2 peak) and exercise bout parameters (intensity and volume) also remain to be clearly elucidated as does the time course of changes after exercise. We performed a meta analysis to assess these potential moderators of the impact of endurance exercise [effect sizes (ESs)] on subsequent Lox at rest (ES = 0.91; 95% CI: 0.69-1.12), on the day of exercise (ES = 1.22; 95% CI: 0.89-1.55), and on the following day (ES = 0.60; 95% CI: 0.35-0.85). ES for the exercise-related increase in resting Lox was significantly greater in men than women in the postabsorptive state but similar in the postprandial state. The ES for depression of RER after exercise was similar between men and women, while the ES for RMR in the postabsorptive state tended to be higher in men than women. Finally, Vo2 peak and exercise energy expenditure (EEE), but not intensity, were predictive of postexercise Lox. The findings indicate importance of EEE and fitness for ability to achieve robust enhancement of Lox after exercise. The results additionally indicate a gender difference in postexercise Lox that is dependent on nutritional state, as the ES for Lox was lower in women only in the postabsorptive state. PMID- 24235103 TI - How important are perturbation responses and joint proprioception to knee osteoarthritis? PMID- 24235104 TI - Changes in breath sound power spectra during experimental oleic acid-induced lung injury in pigs. AB - To evaluate the effect of acute lung injury on the frequency spectra of breath sounds, we made serial acoustic recordings from nondependent, midlung and dependent regions of both lungs in ten 35- to 45-kg anesthetized, intubated, and mechanically ventilated pigs during development of acute lung injury induced with intravenous oleic acid in prone or supine position. Oleic acid injections rapidly produced severe derangements in the gas exchange and mechanical properties of the lung, with an average increase in venous admixture from 16 +/- 12 to 62 +/- 16% (P < 0.01), and a reduction in dynamic respiratory system compliance from 25 +/- 4 to 14 +/- 4 ml/cmH2O (P < 0.01). A concomitant increase in sound power was seen in all lung regions (P < 0.05), predominantly in frequencies 150-800 Hz. The deterioration in gas exchange and lung mechanics correlated best with concurrent spectral changes in the nondependent lung regions. Acute lung injury increases the power of breath sounds likely secondary to redistribution of ventilation from collapsed to aerated parts of the lung and improved sound transmission in dependent, consolidated areas. PMID- 24235106 TI - Lossless compression of RNAi fluorescence images using regional fluctuations of pixels. AB - RNA interference (RNAi) is considered one of the most powerful genomic tools which allows the study of drug discovery and understanding of the complex cellular processes by high-content screens. This field of study, which was the subject of 2006 Nobel Prize of medicine, has drastically changed the conventional methods of analysis of genes. A large number of images have been produced by the RNAi experiments. Even though a number of capable special purpose methods have been proposed recently for the processing of RNAi images but there is no customized compression scheme for these images. Hence, highly proficient tools are required to compress these images. In this paper, we propose a new efficient lossless compression scheme for the RNAi images. A new predictor specifically designed for these images is proposed. It is shown that pixels can be classified into three categories based on their intensity distributions. Using classification of pixels based on the intensity fluctuations among the neighbors of a pixel a context-based method is designed. Comparisons of the proposed method with the existing state-of-the-art lossless compression standards and well-known general-purpose methods are performed to show the efficiency of the proposed method. PMID- 24235105 TI - Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation. AB - It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH accelerate rehabilitation in aging individuals. Elderly men (65-75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF 1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNA expression in muscle, with a difference between GH and Plc. IGF 1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle following immobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagen expression in the musculotendinous tissue and increasing tendon CSA and stiffness. PMID- 24235107 TI - Discriminative and generative classification techniques applied to automated neonatal seizure detection. AB - A number of automated neonatal seizure detectors have been proposed in recent years. However, there exists a large variability in the morphology of seizure and background patterns, both across patients and over time. This has resulted in relatively poor performance from systems which have been tested over large datasets. Here, the benefits of employing a pattern recognition approach are discussed. Such a system may use numerous features paired with nonlinear classifiers. In particular, two types of nonlinear classifiers are contrasted for the task. Additionally, it is shown that the proposed architecture allows for efficient classifier combination which improves the performance of the algorithm. The resulting automated detector is shown to achieve field leading performance. A particular strength of the proposed algorithm is the performance of the algorithm when very low false detections are required, at 0.25 false detections per hour, the system is able to detect 75.4% of the seizure events. PMID- 24235108 TI - Adverse drug effect detection. AB - Large collections of electronic patient records provide abundant but under explored information on the real-world use of medicines. Although they are maintained for patient administration, they provide a broad range of clinical information for data analysis. One growing interest is drug safety signal detection from these longitudinal observational data. In this paper, we proposed two novel algorithms-a likelihood ratio model and a Bayesian network model-for adverse drug effect discovery. Although the performance of these two algorithms is comparable to the state-of-the-art algorithm, Bayesian confidence propagation neural network, the combination of three works better due to their diversity in solutions. Since the actual adverse drug effects on a given dataset cannot be absolutely determined, we make use of the simulated observational medical outcomes partnership (OMOP) dataset constructed with the predefined adverse drug effects to evaluate our methods. Experimental results show the usefulness of the proposed pattern discovery method on the simulated OMOP dataset by improving the standard baseline algorithm-chi-square-by 23.83%. PMID- 24235109 TI - Detection of seizure and epilepsy using higher order statistics in the EMD domain. AB - In this paper, a method using higher order statistical moments of EEG signals calculated in the empirical mode decomposition (EMD) domain is proposed for detecting seizure and epilepsy. The appropriateness of these moments in distinguishing the EEG signals is investigated through an extensive analysis in the EMD domain. An artificial neural network is employed as the classifier of the EEG signals wherein these moments are used as features. The performance of the proposed method is studied using a publicly available benchmark database for various classification cases that include healthy, interictal (seizure-free interval) and ictal (seizure), healthy and seizure, nonseizure and seizure, and interictal and ictal, and compared with that of several recent methods based on time-frequency analysis and statistical moments. It is shown that the proposed method can provide, in almost all the cases, 100% accuracy, sensitivity, and specificity, especially in the case of discriminating seizure activities from the nonseizure ones for patients with epilepsy while being much faster as compared to the time-frequency analysis-based techniques. PMID- 24235110 TI - Coronary vein extraction in MSCT volumes using minimum cost path and geometrical moments. AB - This work deals with the extraction of patient-specific coronary venous anatomy in preoperative multislice computed tomography (MSCT) volumes. A hybrid approach has been specifically designed for low-contrast vascular structure detection. It makes use of a minimum cost path technique with a Fast-Marching front propagation to extract the vessel centerline. A second procedure was applied to refine the position of the path and estimate the local radius along the vessel. This was achieved with an iterative multiscale algorithm based on geometrical moments. Parameter tuning was performed using a dedicated numerical phantom, and then the algorithm was applied to extract the coronary venous system. Results are provided on three MSCT volume sequences acquired for patients selected for a cardiac resynchronization therapy procedure. A visibility study was carried out by a medical expert who labeled venous segments on a set of 18 volumes. A comparison with two other Fast-Marching techniques and a geometrical moment based tracking method is also reported. PMID- 24235111 TI - Toward a passive low-cost in-home gait assessment system for older adults. AB - In this paper, we propose a webcam-based system for in-home gait assessment of older adults. A methodology has been developed to extract gait parameters including walking speed, step time, and step length from a 3-D voxel reconstruction, which is built from two calibrated webcam views. The gait parameters are validated with a GAITRite mat and a Vicon motion capture system in the laboratory with 13 participants and 44 tests, and again with GAITRite for 8 older adults in senior housing. Excellent agreement with intraclass correlation coefficients of 0.99 and repeatability coefficients between 0.7% and 6.6% was found for walking speed, step time, and step length given the limitation of frame rate and voxel resolution. The system was further tested with ten seniors in a scripted scenario representing everyday activities in an unstructured environment. The system results demonstrate the capability of being used as a daily gait assessment tool for fall risk assessment and other medical applications. Furthermore, we found that residents displayed different gait patterns during their clinical GAITRite tests compared to the realistic scenario, namely a mean increase of 21% in walking speed, a mean decrease of 12% in step time, and a mean increase of 6% in step length. These findings provide support for continuous gait assessment in the home for capturing habitual gait. PMID- 24235112 TI - Decision support for subjects exposed to heat stress. AB - The physiological and activity strain index (PASI) has been developed to improve the online decision support for workers exposed to heat stress. Fire fighters (smoke divers) which are exposed to both heat-stress and high-risk situations have been used as test case. PASI combines a modified version of the relatively well-known physiological strain index (PSI) with activity data from accelerometers. The algorithm has been developed based on tests in a laboratory, and it has been verified in two field tests performed by smoke divers exposed to heat stress. The verification demonstrates that it is possible to distinguish between high- and low-risk situations when data from accelerometers are added to the situation analysis. This indicates that PASI can contribute to an improved risk assessment and online decision support for smoke divers compared to using PSI alone. PMID- 24235113 TI - Triaxial accelerometer-based fall detection method using a self-constructing cascade-AdaBoost-SVM classifier. AB - In this paper, we propose a cascade-AdaBoost-support vector machine (SVM) classifier to complete the triaxial accelerometer-based fall detection method. The method uses the acceleration signals of daily activities of volunteers from a database and calculates feature values. By taking the feature values of a sliding window as an input vector, the cascade-AdaBoost-SVM algorithm can self-construct based on training vectors, and the AdaBoost algorithm of each layer can automatically select several optimal weak classifiers to form a strong classifier, which accelerates effectively the processing speed in the testing phase, requiring only selected features rather than all features. In addition, the algorithm can automatically determine whether to replace the AdaBoost classifier by support vector machine. We used the UCI database for the experiment, in which the triaxial accelerometers are, respectively, worn around the left and right ankles, and on the chest as well as the waist. The results are compared to those of the neural network, support vector machine, and the cascade AdaBoost classifier. The experimental results show that the triaxial accelerometers around the chest and waist produce optimal results, and our proposed method has the highest accuracy rate and detection rate as well as the lowest false alarm rate. PMID- 24235114 TI - Child activity recognition based on cooperative fusion model of a triaxial accelerometer and a barometric pressure sensor. AB - This paper presents a child activity recognition approach using a single 3-axis accelerometer and a barometric pressure sensor worn on a waist of the body to prevent child accidents such as unintentional injuries at home. Labeled accelerometer data are collected from children of both sexes up to the age of 16 to 29 months. To recognize daily activities, mean, standard deviation, and slope of time-domain features are calculated over sliding windows. In addition, the FFT analysis is adopted to extract frequency-domain features of the aggregated data, and then energy and correlation of acceleration data are calculated. Child activities are classified into 11 daily activities which are wiggling, rolling, standing still, standing up, sitting down, walking, toddling, crawling, climbing up, climbing down, and stopping. The overall accuracy of activity recognition was 98.43% using only a single- wearable triaxial accelerometer sensor and a barometric pressure sensor with a support vector machine. PMID- 24235115 TI - Autoregressive and iterative hidden Markov models for periodicity detection and solenoid structure recognition in protein sequences. AB - Traditional signal processing methods cannot detect interspersed repeats and generally cannot handle nonstationary signals. In this paper, we propose a new method for periodicity detection in protein sequences to locate interspersed repeats. We first apply the autoregressive model with a sliding window to find possible repeating subsequences within a protein sequence. Then, we utilize an iterative hidden Markov model (HMM) to count the number of subsequences similar to each of the possible repeating subsequences. An iterative HMM search of the potential repeating subsequences can help identify interspersed repeats. Finally, the numbers of repeating subsequences are aggregated together as a feature and used in the classification process. Experiment results show that our method improves the performance of solenoid protein recognition substantially. PMID- 24235116 TI - The tactile sensation imaging system for embedded lesion characterization. AB - Elasticity is an important indicator of tissue health, with increased stiffness pointing to an increased risk of cancer. We investigated a tissue inclusion characterization method for the application of early breast tumor identification. A tactile sensation imaging system (TSIS) is developed to capture images of the embedded lesions using total internal reflection principle. From tactile images, we developed a novel method to estimate that size, depth, and elasticity of the embedded lesion using 3-D finite-element-model-based forward algorithm, and neural-network-based inversion algorithm are employed. The proposed characterization method was validated by the realistic tissue phantom with inclusions to emulate the tumors. The experimental results showed that, the proposed characterization method estimated the size, depth, and Young's modulus of a tissue inclusion with 6.98%, 7.17%, and 5.07% relative errors, respectively. A pilot clinical study was also performed to characterize the lesion of human breast cancer patients using TSIS. PMID- 24235117 TI - Multiscale entropy analysis of different spontaneous motor unit discharge patterns. AB - This study explores a novel application of multiscale entropy (MSE) analysis for characterizing different patterns of spontaneous electromyogram (EMG) signals including sporadic, tonic and repetitive spontaneous motor unit discharges, and normal surface EMG baseline. Two algorithms for MSE analysis, namely, the standard MSE and the intrinsic mode entropy (IMEn) (based on the recently developed multivariate empirical mode decomposition method), were applied to different patterns of spontaneous EMG. Significant differences were observed in multiple scales of the standard MSE and IMEn analyses (<;i>p<;/i> <; 0.001) for any two of the spontaneous EMG patterns, while such significance may not be observed from the single-scale entropy analysis. Compared to the standard MSE, the IMEn analysis facilitates usage of a relatively low scale number to discern entropy difference among various patterns of spontaneous EMG signals. The findings from this study contribute to our understanding of the nonlinear dynamic properties of different spontaneous EMG patterns, which may be related to spinal motoneuron or motor unit health. PMID- 24235118 TI - Temporal properties of diagnosis code time series in aggregate. AB - Time series are essential to health data research and data mining. We aim to study the properties of one of the more commonly available but historically unreliable types of data: administrative diagnoses in the form of the International Classification of Diseases, Ninth Revision (ICD9) codes. We use differential entropy of ICD9 code time series as a surrogate measure for disease time course and also explore Gaussian kernel smoothing to characterize the time course of diseases in a more fine-grained way. Compared to a gold standard created by a panel of clinicians, the first model classified diseases into acute and chronic groups with a receiver operating characteristic area under curve of 0.83. In the second model, several characteristic temporal profiles were observed including permanent, chronic, and acute. In addition, condition dynamics such as the refractory period for giving birth following childbirth were observed. These models demonstrate that ICD9 codes, despite well-documented concerns, contain valid and potentially valuable temporal information. PMID- 24235119 TI - Multiscale adaptive basis function modeling of spatiotemporal vectorcardiogram signals. AB - Mathematical modeling of cardiac electrical signals facilitates the simulation of realistic cardiac electrical behaviors, the evaluation of algorithms, and the characterization of underlying space-time patterns. However, there are practical issues pertinent to model efficacy, robustness, and generality. This paper presents a multiscale adaptive basis function modeling approach to characterize not only temporal but also spatial behaviors of vectorcardiogram (VCG) signals. Model parameters are adaptively estimated by the "best matching" projections of VCG characteristic waves onto a dictionary of nonlinear basis functions. The model performance is experimentally evaluated with respect to the number of basis functions, different types of basis function (i.e., Gaussian, Mexican hat, customized wavelet, and Hermitian wavelets), and various cardiac conditions, including 80 healthy controls and different myocardial infarctions (i.e., 89 inferior, 77 anterior-septal, 56 inferior-lateral, 47 anterior, and 43 anterior lateral). Multiway analysis of variance shows that the basis function and the model complexity have significant effects on model performances while cardiac conditions are not significant. The customized wavelet is found to be an optimal basis function for the modeling of spacetime VCG signals. The comparison of QT intervals shows small relative errors (<;5%) between model representations and realworld VCG signals when the model complexity is greater than 10. The proposed model shows great potentials to model space-time cardiac pathological behaviors and can lead to potential benefits in feature extraction, data compression, algorithm evaluation, and disease prognostics. PMID- 24235120 TI - Acoustic signal classification of breathing movements to virtually aid breath regulation. AB - Monitoring breath and identifying breathing movements have settled importance in many biomedical research areas, especially in the treatment of those with breathing disorders, e.g., lung cancer patients. Moreover, virtual reality (VR) revolution and their implementations on ubiquitous hand-held devices have a lot of implications, which could be used as a simulation technology for healing purposes. In this paper, a novel method is proposed to detect and classify breathing movements. The overall VR framework is intended to encourage the subjects regulate their breath by classifying the breathing movements in real time. This paper focuses on a portion of the overall VR framework that deals with classifying the acoustic signal of respiration movements. We employ Mel-frequency cepstral coefficients (MFCCs) along with speech segmentation techniques using voice activity detection and linear thresholding to the acoustic signal of breath captured using a microphone to depict the differences between inhale and exhale in frequency domain. For every subject, 13 MFCCs of all voiced segments are computed and plotted. The inhale and exhale phases are differentiated using the sixth MFCC order, which carries important classification information. Experimental results on a number of individuals verify our proposed classification methodology. PMID- 24235125 TI - A new twist to the GATA switch. AB - In this issue of Blood, Takai et al provide some tantalizing clues on how expression of the GATA1 transcription factor, a master regulator of erythroid/megakaryocytic differentiation, is suppressed in the hematopoietic stem/progenitor cell (HSPC) compartment. PMID- 24235126 TI - Risky business: target choice in adoptive cell therapy. AB - In this issue of Blood, Casucci et al present an elegant study that describes a potential new target for adoptive cell transfer (ACT), in this case CD44 splice variant 6 (CD44v6), and detail why it may be a good target for ACT and how to manage expected off-tumor/on-target toxicities. PMID- 24235127 TI - The C3a receptor, caspase-1, and release of IL-1beta. AB - In this issue of Blood, Asgari et al report that engagement of the C3a receptor triggers interleukin-1b (IL-1b) processing and release via caspase-1 activation. The role of complement activation in IL-1 production has a long history; complement products function as "alarmins" during innate responses. For many years before the term "innate immune response" was coined, it was fully understood that a highly nonspecific event such as activation of complement would induce a highly nonspecific molecule such as IL-1; these 2 linked processes would then affect a highly specific event such antigen-driven lymphocyte activation, for example, polarization to a T helper 1 (Th1) or a Th17 response. In this issue, investigators link the generation of C3a to playing a role in the activation of caspase-1. A unique and unexpected finding of the study is that engagement of the C3a receptor results in phosphorylation of extracellular signal regulated kinase-1 and 2 (ERK-1/2), which promotes the efflux of adenosine triphosphate (ATP) from the macrophage. Release of ATP is a rate-limiting step for activating caspase-1, as extracellular ATP triggers the P2X7 purinergic receptor to initiate oligomerization of NLRP3. PMID- 24235128 TI - Shedding light on UVR and Hodgkin lymphoma. AB - In this issue of Blood, Monnereau and colleagues pool 4 retrospective (case control), observational epidemiologic studies to demonstrate an inverse association between UV radiation (UVR) exposure and risk of developing Hodgkin lymphoma (HL). PMID- 24235129 TI - In the spotlight: a novel CD37 antibody-drug conjugate. AB - In this issue of Blood, Deckert et al make a strong argument in favor of IMGN529, a novel anti-CD37 maytansinoid antibody-drug conjugate (ADC), elegantly showing its activity against B-cell lymphoma in in vitro and in vivo preclinical studies. PMID- 24235130 TI - Asparaginase unveils glutamine-addicted AML. AB - In this issue of Blood, Willems et al describe the dependence of acute myeloid leukemia (AML) cells on glutamine for maintaining protein synthesis downstream of mammalian target of rapamycin (mTOR) and show that the enzyme asparaginase can be used to target this dependence. Using various AML cell lines, primary samples, and CD341 stem cells from healthy donors, the authors support the notion that asparaginase may offer a therapeutic benefit in AML-not from its well-known enzymatic activity, but from its "off-target" effects on glutamine levels that result in inhibition of downstream mTOR signaling, inhibition of protein synthesis, and ultimately loss of viability. PMID- 24235131 TI - Dengue platelets meet Sir Arthur Conan Doyle. AB - In this issue of Blood, Hottz et al provide compelling evidence that dengue virus (DV) induces (1) platelet synthesis of interleukin-1b (IL-1b); (2) platelet derived IL-1b-containing microvesicles (MVs) that increase vascular permeability; and (3) DV-triggered inflammasome activation in platelets. PMID- 24235132 TI - Machine learning approaches distinguish multiple stress conditions using stress responsive genes and identify candidate genes for broad resistance in rice. AB - Abiotic and biotic stress responses are traditionally thought to be regulated by discrete signaling mechanisms. Recent experimental evidence revealed a more complex picture where these mechanisms are highly entangled and can have synergistic and antagonistic effects on each other. In this study, we identified shared stress-responsive genes between abiotic and biotic stresses in rice (Oryza sativa) by performing meta-analyses of microarray studies. About 70% of the 1,377 common differentially expressed genes showed conserved expression status, and the majority of the rest were down-regulated in abiotic stresses and up-regulated in biotic stresses. Using dimension reduction techniques, principal component analysis, and partial least squares discriminant analysis, we were able to segregate abiotic and biotic stresses into separate entities. The supervised machine learning model, recursive-support vector machine, could classify abiotic and biotic stresses with 100% accuracy using a subset of differentially expressed genes. Furthermore, using a random forests decision tree model, eight out of 10 stress conditions were classified with high accuracy. Comparison of genes contributing most to the accurate classification by partial least squares discriminant analysis, recursive-support vector machine, and random forests revealed 196 common genes with a dynamic range of expression levels in multiple stresses. Functional enrichment and coexpression network analysis revealed the different roles of transcription factors and genes responding to phytohormones or modulating hormone levels in the regulation of stress responses. We envisage the top-ranked genes identified in this study, which highly discriminate abiotic and biotic stresses, as key components to further our understanding of the inherently complex nature of multiple stress responses in plants. PMID- 24235133 TI - Modification of plasma membrane organization in tobacco cells elicited by cryptogein. AB - Lipid mixtures within artificial membranes undergo a separation into liquid disordered and liquid-ordered phases. However, the existence of this segregation into microscopic liquid-ordered phases has been difficult to prove in living cells, and the precise organization of the plasma membrane into such phases has not been elucidated in plant cells. We developed a multispectral confocal microscopy approach to generate ratiometric images of the plasma membrane surface of Bright Yellow 2 tobacco (Nicotiana tabacum) suspension cells labeled with an environment sensitive fluorescent probe. This allowed the in vivo characterization of the global level of order of this membrane, by which we could demonstrate that an increase in its proportion of ordered phases transiently occurred in the early steps of the signaling triggered by cryptogein and flagellin, two elicitors of plant defense reactions. The use of fluorescence recovery after photobleaching revealed an increase in plasma membrane fluidity induced by cryptogein, but not by flagellin. Moreover, we characterized the spatial distribution of liquid-ordered phases on the membrane of living plant cells and monitored their variations induced by cryptogein elicitation. We analyze these results in the context of plant defense signaling, discuss their meaning within the framework of the "membrane raft" hypothesis, and propose a new mechanism of signaling platform formation in response to elicitor treatment. PMID- 24235134 TI - Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1. AB - Niemann-Pick type C (NPC) is a neurodegenerative lysosomal storage disorder caused by defects in the lysosomal proteins NPC1 or NPC2. NPC cells are characterized by reduced lysosomal calcium levels and impaired sphingosine transport from lysosomes. Natural killer (NK) cells kill virally infected/transformed cells via degranulation of lysosome-related organelles. Their trafficking from lymphoid tissues into the circulation is dependent on sphingosine-1-phosphate (S1P) gradients, sensed by S1P receptor 5 (S1P5). We hypothesized that NK-cell function and trafficking could be affected in NPC disease due to the combined effects of the lysosomal calcium defect and sphingosine storage. In an NPC1 mouse model, we found the frequency of NK cells was altered and phenocopied S1P5-deficient mice, consistent with defects in S1P levels. NK cells from NPC1 mice also had a defect in cytotoxicity due to a failure in degranulation of cytotoxic granules, which was associated with reduced lysosomal calcium levels. Affected NPC1 patients and NPC1 heterozygote carriers had reduced NK-cell numbers in their blood and showed similar phenotypic and developmental changes to those observed in the NPC1 mouse. These findings highlight the effects of lysosomal storage on the peripheral immune system. PMID- 24235135 TI - How I treat ALL in Down's syndrome: pathobiology and management. AB - Children with Down syndrome are at high risk for developing B-cell precursor acute lymphoblastic leukemia (DS-ALL) associated with poor outcome due to both a high relapse rate and increased treatment-related mortality (TRM) from infections. Biologically, these heterogeneous leukemias are characterized by under-representation of the common cytogenetic subgroups of childhood ALL and overrepresentation of CRLF2-IL7R-JAK-STAT activating genetic aberrations. Although relapse is the major determinant of poor outcomes in this population, de escalation of chemotherapy intensity might be feasible in the 10% to 15% DS-ALL patients with ETV6-RUNX1 or high hyperdipoidy in whom TRM is the major limiting event. As infection-associated TRM occurs during all treatment phases, including the maintenance period, increased surveillance and supportive care is required throughout therapy. Improvement in outcome will require better understanding of the causes of treatment failure and TRM, incorporation of new therapies targeting the unique biological properties of DS-ALL, and enhanced supportive care measures to reduce the risk of infection-related TRM. To facilitate these goals, an international collaboration plans to establish a prospective DS-ALL registry and develop specific supportive care recommendations for this at-risk population. PMID- 24235136 TI - Functional reconstitution of a chloride channel bares its soul. PMID- 24235137 TI - Single-molecule resolution of protein structure and interfacial dynamics on biomaterial surfaces. AB - A method was developed to monitor dynamic changes in protein structure and interfacial behavior on surfaces by single-molecule Forster resonance energy transfer. This method entails the incorporation of unnatural amino acids to site specifically label proteins with single-molecule Forster resonance energy transfer probes for high-throughput dynamic fluorescence tracking microscopy on surfaces. Structural changes in the enzyme organophosphorus hydrolase (OPH) were monitored upon adsorption to fused silica (FS) surfaces in the presence of BSA on a molecule-by-molecule basis. Analysis of >30,000 individual trajectories enabled the observation of heterogeneities in the kinetics of surface-induced OPH unfolding with unprecedented resolution. In particular, two distinct pathways were observed: a majority population (~ 85%) unfolded with a characteristic time scale of 0.10 s, and the remainder unfolded more slowly with a time scale of 0.7 s. Importantly, even after unfolding, OPH readily desorbed from FS surfaces, challenging the common notion that surface-induced unfolding leads to irreversible protein binding. This suggests that protein fouling of surfaces is a highly dynamic process because of subtle differences in the adsorption/desorption rates of folded and unfolded species. Moreover, such observations imply that surfaces may act as a source of unfolded (i.e., aggregation-prone) protein back into solution. Continuing study of other proteins and surfaces will examine whether these conclusions are general or specific to OPH in contact with FS. Ultimately, this method, which is widely applicable to virtually any protein, provides the framework to develop surfaces and surface modifications with improved biocompatibility. PMID- 24235139 TI - Nuclear recruitment of neuronal nitric-oxide synthase by alpha-syntrophin is crucial for the induction of mitochondrial biogenesis. AB - Neuronal nitric-oxide synthase (nNOS) has various splicing variants and different subcellular localizations. nNOS can be found also in the nucleus; however, its exact role in this compartment is still not completely defined. In this report, we demonstrate that the PDZ domain allows the recruitment of nNOS to nuclei, thus favoring local NO production, nuclear protein S-nitrosylation, and induction of mitochondrial biogenesis. In particular, overexpression of PDZ-containing nNOS (nNOSalpha) increases S-nitrosylated CREB with consequent augmented binding on cAMP response element consensus sequence on peroxisome proliferator-activated receptor gamma co-activator (PGC)-1alpha promoter. The resulting PGC-1alpha induction is accompanied by the expression of mitochondrial genes (e.g., TFAM, MtCO1) and increased mitochondrial mass. Importantly, full active nNOS lacking PDZ domain (nNOSbeta) does not localize in nuclei and fails in inducing the expression of PGC-1alpha. Moreover, we substantiate that the mitochondrial biogenesis normally accompanying myogenesis is associated with nuclear translocation of nNOS. We demonstrate that alpha-Syntrophin, which resides in nuclei of myocytes, functions as the upstream mediator of nuclear nNOS translocation and nNOS-dependent mitochondrial biogenesis. Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment. PMID- 24235140 TI - Bacteriocin protein BacL1 of Enterococcus faecalis is a peptidoglycan D isoglutamyl-L-lysine endopeptidase. AB - Enterococcus faecalis strains are commensal bacteria in humans and other animals, and they are also the causative agent of opportunistic infectious diseases. Bacteriocin 41 (Bac41) is produced by certain E. faecalis clinical isolates, and it is active against other E. faecalis strains. Our genetic analyses demonstrated that the extracellular products of the bacL1 and bacA genes, which are encoded in the Bac41 operon, coordinately express the bacteriocin activity against E. faecalis. In this study, we investigated the molecular functions of the BacL1 and BacA proteins. Immunoblotting and N-terminal amino acid sequence analysis revealed that BacL1 and BacA are secreted without any processing. The coincidental treatment with the recombinant BacL1 and BacA showed complete bacteriocin activity against E. faecalis, but neither BacL1 nor BacA protein alone showed the bacteriocin activity. Interestingly, BacL1 alone demonstrated substantial degrading activity against the cell wall fraction of E. faecalis in the absence of BacA. Furthermore, MALDI-TOF MS analysis revealed that BacL1 has a peptidoglycan D-isoglutamyl-L-lysine endopeptidase activity via a NlpC/P60 homology domain. These results collectively suggest that BacL1 serves as a peptidoglycan hydrolase and, when BacA is present, results in the lysis of viable E. faecalis cells. PMID- 24235141 TI - Increased phagocytosis of Mycobacterium marinum mutants defective in lipooligosaccharide production: a structure-activity relationship study. AB - Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in ectotherms and is an occasional opportunistic human pathogen. In the environment, M. marinum also interacts with amoebae, which may serve as a natural reservoir for this microorganism. However, the description of mycobacterial determinants in the early interaction with macrophages or amoebae remains elusive. Lipooligosaccharides (LOSs) are cell surface-exposed glycolipids capable of modulating the host immune system, suggesting that they may be involved in the early interactions of M. marinum with macrophages. Herein, we addressed whether LOS composition affects the uptake of M. marinum by professional phagocytes. Mutants with various truncated LOS variants were generated, leading to the identification of several previously uncharacterized biosynthetic genes (wbbL2, MMAR_2321, and MMAR_2331). Biochemical and structural approaches allowed resolving the structures of LOS precursors accumulating in this set of mutants. These strains with structurally defined LOS profiles were then used to infect both macrophages and Acanthamoebae. An inverse correlation between LOS completeness and uptake of mycobacteria by phagocytes was found, allowing the proposal of three mutant classes: class I (papA4), devoid of LOS and highly efficiently phagocytosed; class II, accumulating only early LOS intermediates (wbbL2 and MMAR_2331) and efficiently phagocytosed but less than class I mutants; class III, lacking LOS-IV (losA, MMAR_2319, and MMAR_2321) and phagocytosed similarly to the control strain. These results indicate that phagocytosis is conditioned by the LOS pattern and that the LOS pathway used by M. marinum in macrophages is conserved during infection of amoebae. PMID- 24235142 TI - GATA3 transcription factor abrogates Smad4 transcription factor-mediated fascin overexpression, invadopodium formation, and breast cancer cell invasion. AB - Transforming growth factor beta (TGFbeta) is a potent and context-dependent regulator of tumor progression. TGFbeta promotes the lung metastasis of basal like (but not the luminal-like) breast cancer. Here, we demonstrated that fascin, a pro-metastasis actin bundling protein, was a direct target of the canonical TGFbeta-Smad4 signaling pathway in basal-like breast cancer cells. TGFbeta and Smad4 induced fascin overexpression by directly binding to a Smad binding element on the fascin promoter. We identified GATA3, a transcription factor crucial for mammary gland morphogenesis and luminal differentiation, as a negative regulator of TGFbeta- and Smad4-induced fascin overexpression. When ectopically expressed in basal-like breast cancer cells, GATA-3 abrogated TGFbeta- and Smad4-mediated overexpression of fascin and other TGFbeta response genes, invadopodium formation, cell migration, and invasion, suggesting suppression of the canonical TGFbeta-Smad signaling axis. Mechanistically, GATA3 abrogated the canonical TGFbeta-Smad signaling by abolishing interactions between Smad4 and its DNA binding elements, potentially through physical interactions between the N terminal of GATA3 and Smad3/4 proteins. Our findings provide mechanistic insight into how TGFbeta-mediated cell motility and invasiveness are differentially regulated in breast cancer. PMID- 24235143 TI - Bone morphogenetic proteins signal via SMAD and mitogen-activated protein (MAP) kinase pathways at distinct times during osteoclastogenesis. AB - To investigate the role of bone morphogenetic protein (BMP) signaling in osteoclastogenesis in vivo, we eliminated BMPRII in osteoclasts by creating a BMPRII(fl/fl);lysM-Cre mouse strain. Conditional knock-out (cKO) mice are osteopetrotic when compared with WT controls due to a decrease in osteoclast activity. Bone marrow macrophages (BMMs) isolated from cKO mice are severely inhibited in their capacity to differentiate into mature osteoclasts in the presence of M-CSF and receptor activator of NF-kappaB (RANK) ligand. We also show that BMP noncanonical (MAPK) and canonical (SMAD) pathways are utilized at different stages of osteoclast differentiation. BMP2 induces p38 phosphorylation in pre-fusion osteoclasts and increases SMAD phosphorylation around osteoclast precursor fusion. Phosphorylation of MAPKs was decreased in differentiated BMMs from cKO animals. Treating BMMs with the SMAD inhibitor dorsomorphin confirms the requirement for the canonical pathway around the time of fusion. These results demonstrate the requirement for BMP signaling in osteoclasts for proper bone homeostasis and also explore the complex signaling mechanisms employed by BMP signaling during osteoclast differentiation. PMID- 24235144 TI - Ca2+-independent binding of anionic phospholipids by phospholipase C delta1 EF hand domain. AB - Recombinant EF-hand domain of phospholipase C delta1 has a moderate affinity for anionic phospholipids in the absence of Ca(2+) that is driven by interactions of cationic and hydrophobic residues in the first EF-hand sequence. This region of PLC delta1 is missing in the crystal structure. The relative orientation of recombinant EF with respect to the bilayer, established with NMR methods, shows that the N-terminal helix of EF-1 is close to the membrane interface. Specific mutations of EF-1 residues in full-length PLC delta1 reduce enzyme activity but not because of disturbing partitioning of the protein onto vesicles. The reduction in enzymatic activity coupled with vesicle binding studies are consistent with a role for this domain in aiding substrate binding in the active site once the protein is transiently anchored at its target membrane. PMID- 24235145 TI - Automethylation activities within the mixed lineage leukemia-1 (MLL1) core complex reveal evidence supporting a "two-active site" model for multiple histone H3 lysine 4 methylation. AB - The mixed lineage leukemia-1 (MLL1) core complex predominantly catalyzes mono- and dimethylation of histone H3 at lysine 4 (H3K4) and is frequently altered in aggressive acute leukemias. The molecular mechanisms that account for conversion of mono- to dimethyl H3K4 (H3K4me1,2) are not well understood. In this investigation, we report that the suppressor of variegation, enhancer of zeste, trithorax (SET) domains from human MLL1 and Drosophila Trithorax undergo robust intramolecular automethylation reactions at an evolutionarily conserved cysteine residue in the active site, which is inhibited by unmodified histone H3. The location of the automethylation in the SET-I subdomain indicates that the MLL1 SET domain possesses significantly more conformational plasticity in solution than suggested by its crystal structure. We also report that MLL1 methylates Ash2L in the absence of histone H3, but only when assembled within a complex with WDR5 and RbBP5, suggesting a restraint for the architectural arrangement of subunits within the complex. Using MLL1 and Ash2L automethylation reactions as probes for histone binding, we observed that both automethylation reactions are significantly inhibited by stoichiometric amounts of unmethylated histone H3, but not by histones previously mono-, di-, or trimethylated at H3K4. These results suggest that the H3K4me1 intermediate does not significantly bind to the MLL1 SET domain during the dimethylation reaction. Consistent with this hypothesis, we demonstrate that the MLL1 core complex assembled with a catalytically inactive SET domain variant preferentially catalyzes H3K4 dimethylation using the H3K4me1 substrate. Taken together, these results are consistent with a "two-active site" model for multiple H3K4 methylation by the MLL1 core complex. PMID- 24235146 TI - Angiopoietin-2 secretion by endothelial cell exosomes: regulation by the phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) and syndecan-4/syntenin pathways. AB - Angiopoietin-2 (Ang2) is an extracellular protein and one of the principal ligands of Tie2 receptor that is involved in the regulation of vascular integrity, quiescence, and inflammation. The mode of secretion of Ang2 has never been established, however. Here, we provide evidence that Ang2 is secreted from endothelial cells via exosomes and that this process is inhibited by the PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway, whereas it is positively regulated by the syndecan-4/syntenin pathway. Vascular defects in Akt1 null mice arise, in part, because of excessive Ang2 secretion and can be rescued by the syndecan-4 knock-out that reduces extracellular Ang2 levels. This novel mechanism connects three critical signaling pathways: angiopoietin/Tie2, PI3K/Akt/eNOS, and syndecan/syntenin, which play important roles in vascular growth and stabilization. PMID- 24235147 TI - Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation. AB - Circadian rhythm is a biological rhythm governing physiology and behavior with a period of ~24 h. At the molecular level, circadian output is controlled by a molecular clock composed of positive and negative feedback loops in transcriptional and post-translational processes. CLOCK is a transcription factor known as a central component of the molecular clock feedback loops generating circadian oscillation. Although CLOCK is known to undergo multiple post translational modifications, the knowledge of their entities remains limited. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine-threonine kinase that is involved in various neuronal processes. Here, we report that Cdk5 is a novel regulator of CLOCK protein. Cdk5 phosphorylates CLOCK at the Thr-451 and Thr-461 residues in association with transcriptional activation of CLOCK. The Cdk5-dependent regulation of CLOCK function is mediated by alterations of its stability and subcellular distribution. These results suggest that Cdk5 is a novel regulatory component of the core molecular clock machinery. PMID- 24235148 TI - Tubulation of endosomal structures in human dendritic cells by Toll-like receptor ligation and lymphocyte contact accompanies antigen cross-presentation. AB - Mouse dendritic cells (DCs) can rapidly extend their Class II MHC-positive late endosomal compartments into tubular structures, induced by Toll-like receptor (TLR) triggering. Within antigen-presenting DCs, tubular endosomes polarize toward antigen-specific CD4(+) T cells, which are considered beneficial for their activation. Here we describe that also in human DCs, TLR triggering induces tubular late endosomes, labeled by fluorescent LDL. TLR triggering was insufficient for induced tubulation of transferrin-positive endosomal recycling compartments (ERCs) in human monocyte-derived DCs. We studied endosomal remodeling in human DCs in co-cultures of DCs with CD8(+) T cells. Tubulation of ERCs within human DCs requires antigen-specific CD8(+) T cell interaction. Tubular remodeling of endosomes occurs within 30 min of T cell contact and involves ligation of HLA-A2 and ICAM-1 by T cell-expressed T cell receptor and LFA-1, respectively. Disintegration of microtubules or inhibition of endosomal recycling abolished tubular ERCs, which coincided with reduced antigen-dependent CD8(+) T cell activation. Based on these data, we propose that remodeling of transferrin-positive ERCs in human DCs involves both innate and T cell-derived signals. PMID- 24235149 TI - A novel Pex14 protein-interacting site of human Pex5 is critical for matrix protein import into peroxisomes. AB - Protein import into peroxisomes relies on the import receptor Pex5, which recognizes proteins with a peroxisomal targeting signal 1 (PTS1) in the cytosol and directs them to a docking complex at the peroxisomal membrane. Receptor-cargo docking occurs at the membrane-associated protein Pex14. In human cells, this interaction is mediated by seven conserved diaromatic penta-peptide motifs (WXXX(F/Y) motifs) in the N-terminal half of Pex5 and the N-terminal domain of Pex14. A systematic screening of a Pex5 peptide library by ligand blot analysis revealed a novel Pex5-Pex14 interaction site of Pex5. The novel motif composes the sequence LVAEF with the evolutionarily conserved consensus sequence LVXEF. Replacement of the amino acid LVAEF sequence by alanines strongly affects matrix protein import into peroxisomes in vivo. The NMR structure of a complex of Pex5 (57-71) with the Pex14-N-terminal domain showed that the novel motif binds in a similar alpha-helical orientation as the WXXX(F/Y) motif but that the tryptophan pocket is now occupied by a leucine residue. Surface plasmon resonance analyses revealed 33 times faster dissociation rates for the LVXEF ligand when compared with a WXXX(F/Y) motif. Surprisingly, substitution of the novel motif with the higher affinity WXXX(F/Y) motif impairs protein import into peroxisomes. These data indicate that the distinct kinetic properties of the novel Pex14-binding site in Pex5 are important for processing of the peroxisomal targeting signal 1 receptor at the peroxisomal membrane. The novel Pex14-binding site may represent the initial tethering site of Pex5 from which the cargo-loaded receptor is further processed in a sequential manner. PMID- 24235152 TI - Tuberculous meningitis. PMID- 24235150 TI - Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. AB - Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau. PMID- 24235153 TI - The component structure of event-related potentials in the p300 speller paradigm. AB - We investigated the componential structure of event-related potentials elicited while participants use the P300 BCI. Six healthy participants "typed" all characters in a 6 * 6 matrix twice in a random sequence. A principal component analysis indicated that in addition to the P300, target flashes elicited an earlier frontal positivity, possibly a Novelty P3. The amplitudes of both P300 and the Novelty P3 varied with the matrix row in which the target character was located. However, the P300 elicited by row flashes was largest for targets in the lower part of the matrix, whereas the Novelty P3 elicited by column flashes was largest in the top part. Classification accuracy using stepwise linear discriminant analysis mirrored the pattern in the Novelty P3 (an accuracy difference of 0.1 between rows 1 and 6). When separate classifiers were generated to rely solely on the P300 or solely on the Novelty P3, the latter function led to higher accuracy (a mean accuracy difference of about 0.2 between classifiers). A possible explanation is that some nontarget flashes elicit a P300, leading to lower selection accuracy of the respective classifier. In an additional set of data from six different participants we replicated the ERP structure of the initial analyses and characterized the spatial distributions more closely by using a dense electrode array. Overall, our findings provide new insights in the componential structure of ERPs elicited in the P300 speller paradigm and have important implications for optimizing the speller's selection accuracy. PMID- 24235151 TI - Gel-based protease proteomics for identifying the novel calpain substrates in dopaminergic neuronal cell. AB - Calpains are a family of calcium-dependent cysteine proteases that are ubiquitously expressed in mammals and play critical roles in neuronal death by catalyzing substrate proteolysis. Here, we developed two-dimensional gel electrophoresis-based protease proteomics to identify putative calpain substrates. To accomplish this, cellular lysates from neuronal cells were first separated by pI, and the immobilized sample on a gel strip was incubated with a recombinant calpain and separated by molecular weight. Among 25 altered protein spots that were differentially expressed by at least 2-fold, we confirmed that arsenical pump-driving ATPase, optineurin, and peripherin were cleaved by calpain using in vitro and in vivo cleavage assays. Furthermore, we found that all of these substrates were cleaved in MN9D cells treated with either ionomycin or 1 methyl-4-phenylpyridinium, both of which cause a calcium-mediated calpain activation. Their cleavage was blocked by calcium chelator or calpain inhibitors. In addition, calpain-mediated cleavage of these substrates and its inhibition by calpeptin were confirmed in a middle cerebral artery occlusion model of cerebral ischemia, as well as a stereotaxic brain injection model of Parkinson disease. Transient overexpression of each protein was shown to attenuate 1-methyl-4 phenylpyridinium-induced cell death, indicating that these substrates may confer protection of varying magnitudes against dopaminergic injury. Taken together, the data indicate that our protease proteomic method has the potential to be applicable for identifying proteolytic substrates affected by diverse proteases. Moreover, the results described here will help us decipher the molecular mechanisms underlying the progression of neurodegenerative disorders where protease activation is critically involved. PMID- 24235159 TI - Psychiatric discourse in the wake of the Editor's retirement. PMID- 24235160 TI - The Adelaide Pre-vocational Psychiatry Programme: meaningful psychiatry training for pre-vocational doctors. PMID- 24235161 TI - In memoriam: Asperger's. PMID- 24235162 TI - Behaviour theory and attachment theory. PMID- 24235163 TI - Australia's gardens, slugs and snails: the risks of pica and rat-lungworm infection. PMID- 24235176 TI - The short and very short forms of the Children's Behavior Questionnaire in a community sample of preschoolers. AB - The aim was to test the internal structure of scores on the short and very short forms of the Children's Behavior Questionnaire (CBQ) scale and to study the relationship between the dimensions derived and external variables previously related to extreme temperament in a Spanish community sample. The sample comprised of 622 three-year-old children participating in a longitudinal study. Data were obtained from parents and teachers through a semistructured diagnostic interview and questionnaires evaluating children's characteristics and psychological states. Results showed a three-factor structure and moderate reliability of the scale scores for both the short and very short forms. Associations were found between the Surgency/Extraversion dimension and attention deficit/hyperactivity disorder and externalizing problems, between Negative Affect and internalizing and emotional problems, and between Effortful Control and attention, externalizing, and social problems and other executive function measures. Salient temperamental characteristics predicted psychopathological disorders and impairment at ages 3 and 4. The short forms of the CBQ provide reliable and valid scores for assessing temperamental characteristics in the preschool years. PMID- 24235177 TI - Cross-validation study using item response theory: the health-related quality of life for eating disorders questionnaire-short version. AB - The Health-Related Quality of Life for Eating Disorder-Short questionnaire is one of the most suitable existing instruments for measuring quality of life in patients with eating disorders. The objective of the study was to evaluate its reliability, validity, and responsiveness in a cohort of 377 patients. A comprehensive validation process was performed, including confirmatory factor analysis and a graded response model, and assessments of reliability and responsiveness at 1 year of follow-up. The confirmatory factor analysis confirmed the two second-order latent traits, social maladjustment, and mental health and functionality. The graded response model results showed that all items were good for discriminating their respective latent traits. Cronbach's alpha coefficients were high, and responsiveness parameters showed moderate changes. In conclusion, this short questionnaire has good psychometric properties. Its simplicity and ease of application further enhance its acceptability and usefulness in clinical research and trials, as well as in routine practice. PMID- 24235178 TI - Violations of Assumptions in School-Based Single-Case Data: Implications for the Selection and Interpretation of Effect Sizes. AB - A wide variety of effect sizes (ESs) has been used in the single-case design literature. Several researchers have "stress tested" these ESs by subjecting them to various degrees of problem data (e.g., autocorrelation, slope), resulting in the conditions by which different ESs can be considered valid. However, on the back end, few researchers have considered how prevalent and severe these problems are in extant data and as a result, how concerned applied researchers should be. The current study extracted and aggregated indicators of violations of normality and independence across four domains of educational study. Significant violations were found in total and across fields, including low levels of autocorrelation and moderate levels of absolute trend. These violations affect the selection and interpretation of ESs at the individual study level and for meta-analysis. Implications and recommendations are discussed. PMID- 24235179 TI - Ups and downs of evidence and practice guidelines. PMID- 24235181 TI - Caring for the carers: role of the chaplain in an interprofessional academic family medicine practice. PMID- 24235182 TI - Defining and measuring a palliative approach in primary care. PMID- 24235185 TI - Is evidence-based medicine overrated in family medicine?: Yes. PMID- 24235186 TI - Is evidence-based medicine overrated in family medicine?: No. PMID- 24235190 TI - Botulinum toxin type A in pregnancy. AB - QUESTION: My patient received 62 units of botulinum toxin type A (BTX-A) for facial lines. Two weeks later, she found out that she was pregnant. Will this cause any harm to her fetus? ANSWER: Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus. PMID- 24235189 TI - Approach to identifying and managing atherogenic dyslipidemia: a metabolic consequence of obesity and diabetes. AB - OBJECTIVE: To review the evidence for recognition and management of atherogenic dyslipidemia. SOURCES OF INFORMATION: High-quality randomized trials and meta analyses were available to address most questions. North American and European guidelines were reviewed. Of these, the Canadian Cardiovascular Society lipid guidelines were most congruent with current literature. MAIN MESSAGE: Atherogenic dyslipidemia is characterized by low levels of high-density lipoprotein (HDL), high levels of triglycerides, and a high low-density lipoprotein (LDL) particle number. The condition is highly associated with cardiovascular disease (CVD) and is poorly reflected in Framingham risk score and LDL measurements. Obesity, glucose intolerance, diabetes, and metabolic syndrome are rapidly becoming more common, and are often associated with atherogenic dyslipidemia, affecting long term CVD risk. Recognition in the office is best achieved by non-HDL or total cholesterol-HDL ratio testing. Treatment success lies in optimizing diet and exercise. Of available medications, statins produce the most benefit and can be titrated to patient tolerance rather than to LDL target levels, which have a poor evidence base. The addition of fenofibrate can be considered in patients with high triglyceride and low HDL levels who have responded poorly to or have not tolerated statins. CONCLUSION: Growing obesity prevalence creates a CVD risk that might be missed by LDL cholesterol testing alone. Simple calculations from results of a non-fasting lipid panel produce non-HDL levels and total cholesterol HDL ratio, both of which are superior for predicting risk in all patients. These metrics should be available in lipid panels. PMID- 24235192 TI - Type 2 diabetes and hemoglobin A1c targets. PMID- 24235191 TI - Treatment and prevention of ophthalmia neonatorum. AB - QUESTION: In my office I occasionally see neonates with conjunctivitis. What are the current recommendations for ocular prophylaxis at birth? Do topical antibiotics alone provide adequate treatment of neonatal conjunctivitis? When is systemic therapy indicated? ANSWER: All infants should receive ocular prophylaxis at birth to prevent gonococcal ophthalmia. Neonates presenting with signs of conjunctivitis should have a conjunctival swab sent for Gram stain and culture. If Gram-negative diplococci are present on the Gram stain results, the infants and their parents should be treated immediately for presumed gonorrhea. Infants with chlamydial infection should be treated with oral antibiotics. Most of all other forms of bacterial conjunctivitis can be treated with topical antibiotics, with the exception of Pseudomonas infection. Infants should be followed during their treatment and upon completion of therapy to ensure resolution of symptoms. For cases in which sexually transmitted bacteria are implicated, the mothers and their sexual partners should be treated. PMID- 24235193 TI - Uncommon, sinister vertebral fracture: early-onset multiple myeloma. PMID- 24235194 TI - Indirect laryngoscopy. PMID- 24235197 TI - President's message: passing the baton. PMID- 24235195 TI - Family-centred care delivery: comparing models of primary care service delivery in Ontario. AB - OBJECTIVE: To determine whether models of primary care service delivery differ in their provision of family-centred care (FCC) and to identify practice characteristics associated with FCC. DESIGN: Cross-sectional study. SETTING: Primary care practices in Ontario (ie, 35 salaried community health centres, 35 fee-for-service practices, 32 capitation-based health service organizations, and 35 blended remuneration family health networks) that belong to 4 models of primary care service delivery. PARTICIPANTS: A total of 137 practices, 363 providers, and 5144 patients. MAIN OUTCOME MEASURES: Measures of FCC in patient and provider surveys were based on the Primary Care Assessment Tool. Statistical analyses were conducted using linear mixed regression models and generalized estimating equations. RESULTS: Patient-reported FCC scores were high and did not vary significantly by primary care model. Larger panel size in a practice was associated with lower odds of patients reporting FCC. Provider-reported FCC scores were significantly higher in community health centres than in family health networks (P = .035). A larger number of nurse practitioners and clinical services on-site were both associated with higher FCC scores, while scores decreased as the number of family physicians in a practice increased and if practices were more rural. CONCLUSION: Based on provider and patient reports, primary care reform strategies that encourage larger practices and more patients per family physician might compromise the provision of FCC, while strategies that encourage multidisciplinary practices and a range of services might increase FCC. PMID- 24235200 TI - Cumulative profile: rural FPs: an endangered species? PMID- 24235201 TI - Rebuttal: Is evidence-based medicine overrated in family medicine?: Yes. PMID- 24235202 TI - Rebuttal: Is evidence-based medicine overrated in family medicine?: No. PMID- 24235207 TI - Curriculum to enhance pharmacotherapeutic knowledge in family medicine: interprofessional coteaching and web-based learning. AB - PROBLEM ADDRESSED: Prescribing is an essential skill for physicians. Despite the fact that prescribing habits are still developing in residency, formal pharmacotherapy curricula are not commonplace in postgraduate programs. OBJECTIVE OF PROGRAM: To teach first-year and second-year family medicine residents a systematic prescribing process using a medication prescribing framework, which could be replicated and distributed. PROGRAM DESCRIPTION: A hybrid model of Web based (www.rationalprescribing.com) and in-class seminar learning was used. Web based modules, consisting of foundational pharmacotherapeutic content, were each followed by an in-class session, which involved applying content to case studies. A physician and a pharmacist were coteachers and they used simulated cases to enhance application of pharmacotherapeutic content and modeled interprofessional collaboration. CONCLUSION: This systematic approach to prescribing was well received by family medicine residents. It might be important to introduce the process in the undergraduate curriculum-when learners are building their therapeutic foundational knowledge. Incorporating formal pharmacotherapeutic curriculum into residency teaching is challenging and requires further study to identify potential effects on prescribing habits. PMID- 24235208 TI - Front-office staff can improve clinical tobacco intervention: health coordinator pilot project. AB - OBJECTIVE: To learn whether front-line personnel in primary care practices can increase delivery of clinical tobacco interventions and also help smokers address physical inactivity, at-risk alcohol use, and depression. DESIGN: Uncontrolled before-and-after design. SETTING: Vancouver, BC, area (4 practices); northern British Columbia (2 practices). PARTICIPANTS: Six practices, with 1 staff person per practice serving as a "health coordinator" who tracked and, after the baseline period, delivered preventive interventions to all patients who smoked. To assess delivery of preventive interventions, each practice was to sample 300 consecutive patient records, both at baseline and at follow-up 15 months later. INTERVENTIONS: Front-office staff were recruited, trained, paid, and given ongoing support to provide preventive care. Clinicians supplemented this care with advice and guided the use of medication. MAIN OUTCOME MEASURES: Effectiveness of the intervention was based on comparison, at baseline and at follow-up, of the proportion of patients with any of the following 6 proven intervention components documented in their medical records: chart reminder, advice received, self-management plan, target quit date, referral, and follow-up date (as they applied to tobacco, physical inactivity, at-risk alcohol use, and depression). A Tobacco Intervention Flow Sheet cued preventive care, and its data were entered into a spreadsheet (which served as a smokers' registry). Qualitative appraisal data were noted. RESULTS: For tobacco, substantial increases occurred after the intervention period in the proportion of patients with each of the intervention components noted in their charts: chart reminder (20% vs 94%); provision of advice (34% vs 79%); self-management plan (14% vs 57%); target quit date (5% vs 11%); referral (6% vs 11%); and follow-up date (7% vs 42%). Interventions for physical inactivity and depression showed some gains, but there were no gains for at-risk alcohol use. Front-line staff, patients, and clinicians were enthusiastic about the services offered. CONCLUSION: Selected front-office personnel can substantially increase the delivery of evidence-based clinical tobacco intervention and increase patient and staff satisfaction in doing so. How far these findings can be generalized and their population effects require further study. PMID- 24235209 TI - Qualitative study of employment of physician assistants by physicians: benefits and barriers in the Ontario health care system. AB - OBJECTIVE: To explore the experiences and perceptions of Ontario physician assistant (PA) employers about the barriers to and benefits of hiring PAs. DESIGN: A qualitative design using semistructured interviews. SETTING: Rural and urban eastern and southwestern Ontario. PARTICIPANTS: Seven family physicians and 7 other specialists. METHODS: The 14 physicians participated in semistructured interviews, which were audiorecorded and transcribed verbatim. An iterative approach using immersion and crystallization was employed for analysis. MAIN FINDINGS: Physician-specific benefits to hiring PAs included increased flexibility, the opportunity to expand practice, the ability to focus more time on complex patients, overall reduction in work hours and stress, and an opportunity for professional fellowship. Physicians who hired PAs without government financial support said PAs were affordable as long as they were able to retain them. Barriers to hiring PAs included uncertainty about funding, the initial need for intensive supervision and training, and a lack of clarity around delegation of acts. CONCLUSION: Physicians are motivated to hire PAs to help deal with long wait times and long hours, but few are expecting to increase their income by taking on PAs. Governments, medical colleges, educators, and regulators must address the perceived barriers to PA hiring in order to expand and optimize this profession. PMID- 24235210 TI - Who knows more about immunization?: Survey of public health nurses and physicians. AB - OBJECTIVE: To report the findings of a knowledge survey of nurse and physician immunization providers. DESIGN: Cross-sectional postal survey assessing demographic characteristics and vaccine knowledge. SETTING: British Columbia (BC). PARTICIPANTS: Nurse and physician immunization providers in BC. MAIN OUTCOME MEASURES: Knowledge of vaccine-preventable diseases, vaccines in general, and vaccine administration and handling practices. RESULTS: Survey responses were received from 256 nurses and 292 physicians (response rates of 48.6% and 18.3%, respectively). Most nurses (98.4%) reported receiving immunization training outside of the academic setting compared with 55.6% of physicians. Overall, nurse immunizers scored significantly higher than physician immunizers on all 3 domains of immunization knowledge (83.7% vs 72.8%, respectively; P < .001). Physicians scored highest on the vaccine-preventable disease domain and least well on the general vaccine domain. Nurses with more experience as health care providers scored higher. Physicians scored higher if they were female, served patient populations predominantly younger than 5 years, or received immunization training outside of academic settings. CONCLUSION: In BC, nurse immunizers appear to have higher overall immunization knowledge than physicians and are more likely to receive immunization training when in practice. Physician immunizers might benefit most from further training on vaccines and vaccine administration and handling. PMID- 24235211 TI - Patient-centred interviewing and evidence-based patient counseling. PMID- 24235213 TI - Identification of a natural source for the OR37B ligand. AB - In search for biological sources of the long-chain fatty aldehydes (penta-, hexa , and heptadecanal), which we recently identified as ligands for members of the mouse odorant receptor subfamily OR37, the headspace of secretions and excretions from mice was analyzed by gas chromatography and mass spectrometry. In urine, skin swabs, and saliva, these components were not detectable. However, in fecal pellets, a substantial amount of hexadecanal, the OR37B ligand, was found. Accordingly, exposure of mice to feces induced an activation of the OR37B glomerulus, whereas the OR37A and the OR37C glomerulus were not responsive. The amount of hexadecanal deposited with feces varied significantly; however, it was independent of the amount of feed. In many species, feces is covered with secretion from anal glands. Due to the size and the inaccessibility of these glands in mice, the headspace of anal gland secretion from dog was analyzed by gas chromatography-mass spectrometry, which resulted in a prominent peak for hexadecanal. Exposure of mice to anal gland secretion from dog activated the OR37B glomerulus. Altogether, these data suggest that hexadecanal, a ligand for the receptor OR37B, is produced in anal glands and deposited with feces into the environment. PMID- 24235215 TI - The impact of broiler production system practices on consumer perceptions of animal welfare. AB - This research explores the extent to which different farm management practices influence the perceived animal friendliness of broiler production systems, and how this differs between individuals. Using a conjoint design with paired comparisons, respondents evaluated broiler production systems that were described on the basis of 7 animal welfare-related practices. It was found that practices in the area of outdoor access, stocking density, and day-night rhythm were overall perceived to have a larger impact on perceptions of animal friendliness than other practices, such as transport duration or the type of breed used. However, individuals differed regarding the extent to which they believed the different farm management practices influenced the animal friendliness of the production system. Differences between individuals regarding their knowledge about and familiarity with livestock farming, degree of anthropomorphism, and their moral beliefs regarding animal welfare partly explained the relative importance individuals attached to farm management practices. The obtained insight into which welfare-related farm management practices, in consumers' minds, most strongly contribute to animal welfare, and the existence of differences between consumers, can be helpful in the development of animal welfare-based certification schemes that are appealing to consumers, as well as the positioning of welfare concepts in the market. PMID- 24235214 TI - Increasing dietary vitamin D3 improves the walking ability and welfare status of broiler chickens reared at high stocking densities. AB - A study was conducted to evaluate the effects of varying dietary vitamin D3 and stocking density on growing performance, carcass characteristics, bone biomechanical properties, and welfare responses in Ross (308) broilers. Experimental diets, containing 1, 10, or 20 times the NRC recommended level of vitamin D3 (200 IU/kg), were formulated with low, medium, or high vitamin D3 levels for 3 growing phases. Two stocking densities were 10 and 16 birds/m(2). One-day-old hatchlings (1,872 males) were randomly assigned to 6 pens in each treatment. Results showed that high stocking density decreased the feed intake, BW gain (P < 0.01), breast muscle yield (P = 0.010), and tibial development (P < 0.01), whereas increasing feed conversion ratio (P < 0.001), and the scores of gait, footpad and hock burn, and abdominal plumage damage (P < 0.01), particularly toward the age when birds attained their market size. Increasing dietary vitamin D3 improved the birds' walking ability and tibial quality (P < 0.05), and reduced the development of footpad or hock dermatitis and abdominal plumage damage (P < 0.01), some aspects of which were age-dependent and appeared to vary with stocking density. These data indicate that increasing supplemental vitamin D3 has a favorable effect on walking ability and welfare status of high stocking density birds, but not on performance. PMID- 24235216 TI - No evidence of temperature-dependent sex determination or sex-biased embryo mortality in the chicken. AB - Skewing the sex ratio at hatch in commercial poultry would be economically beneficial to the poultry industry. The existence of temperature-dependent sex determination is uncertain in birds. This experiment investigated if incubation temperatures skew sex ratios of commercial broilers. Three incubators were each set at a hot (38.3 degrees C), standard (37.5 degrees C), or cool (36.7 degrees C) single-stage incubation temperature one time over 3 trials to eliminate incubator effect as a Latin square design. Sex ratios of hatched chicks and dead embryos were monitored. In one trial, embryo weights were evaluated. The percentages of male hatched chicks did not differ based on incubation temperature (P = 0.4486; 49.5% in the hot treatment, 51.4% at standard temperature, and 49.8% in the cool treatment). The percent hatch of eggs set was lower in the hot treatment (83.6%) than the standard (93.5%) and cool (91.6%) treatments (P < 0.0001) with greater late embryonic mortality in the hot treatment (P < 0.0001); however, the sex ratio of dead embryos did not differ among treatments (P = 0.9863). Pooled data of embryo mortality found no sex-biased embryo mortality with a female/male sex ratio of 1.22:1 (chi(2) = 1.27; P = 0.2596). Embryos from the hot treatment were heavier than those from the standard treatment by d 14 of incubation and were heavier than the embryos from the cool treatment by d 9 of incubation (P < 0.0001). These data indicate that incubation temperature affects embryonic mortality and embryonic growth rate, but it does not affect the sex ratio of broiler chickens. Additionally, no evidence was found for sex-biased embryo mortality in commercial broilers even at the incubation temperatures of this study. PMID- 24235217 TI - The effects of light stimulation during incubation on indicators of stress susceptibility in broilers. AB - Providing light during incubation has been shown to decrease bilateral physical asymmetry of broilers posthatch, which may indicate that early light stimulation reduces later stress susceptibility. This experiment evaluated the effects of lighting during embryogenesis on other measures of stress responsiveness in broilers. Cobb 500 eggs (n = 1,404) were incubated under 0L:24D, 1L:23D, 6L:18D, or 12L:12D; the light level was 550 lx. The broilers were then raised in floor pens under a 12L:12D lighting regimen, and various stress parameters were measured during wk 3 to 6 of age. There was an effect of incubation lighting regimen on posthatch stress responses. Following 1 h of crating, the change in corticosterone (CORT) concentration was less in the 12L:12D (-0.06 ng/mL, P < 0.05) treatment than all other treatments (pooled mean = 0.24 ng/mL); however, there were no treatment differences in CORT response to adrenocorticotropic hormone administration (pooled mean pre- vs. 1 h postadministration = 17.5 ng/mL, P > 0.05). Anti-keyhole limpet hemocyanin titers were higher in the 12L:12D birds (92,395 units/mL; P < 0.05) than all other treatments (pooled mean = 68,407 units/mL) on d 1 postcrating. Additionally, composite asymmetry scores were lower in the 12L:12D treatment (0.92 mm) than all other treatments (pooled mean = 1.14 mm, P < 0.05). These results demonstrate that providing 12 h of light per day during incubation can reduce the stress susceptibility of broilers posthatch. PMID- 24235218 TI - The detection and elimination of flavin-containing monooxygenase 3 gene T329S mutation in the Beijing You chicken. AB - In this study, using a newly developed TaqMan-based real-time PCR method for the T329S mutation in the flavin-containing monooxygenase 3 (FMO3) gene, a marker assisted selective breeding program against the unfavorable T allele was implemented in the Beijing You chicken breeding stock from 2010 to 2012. A total of 2,359 breeder candidate chickens were detected. After 1-generation culling in both males and females and 2-generation culling only in males, genotyping results in 2013 showed that there still remained a low unfavorable allele frequency of 0.022 in this population. The results indicated that to ensure a complete eradication of the defective tainting mutation in FMO3 out of the Beijing You population, more strict breeding and management schemes should be carried out in the future. PMID- 24235219 TI - Abundant polymorphisms at the microsatellite locus LEI0258 in indigenous chickens. AB - The chicken major histocompatibility complex (MHC) has abundant SNP and indels, and is closely related with host genetic resistance or susceptibility to disease. The LEI0258 locus is the most variable in the MHC region, and is a useful marker in reflecting the variability of MHC. In this study, we applied the LEI0258 microsatellite marker to investigate polymorphism of MHC in Chinese indigenous chickens. The size of LEI0258 fragments in 1,617 individuals from 33 Chinese chicken breeds was detected by capillary electrophoresis, and 213 samples with different fragment sizes were further sequenced. A total of 69 alleles ranging from 193 to 489 bp were found, including 21 novel alleles and 28 private alleles that existed in only one breed. Three alleles, 249 bp (7.04%), 489 bp (6.57%), and 309 bp (6.10%), were the most frequent in the indigenous chickens. A 489-bp novel allele was unique in Chinese local chicken breeds. Three indels and 4 SNP of upstream/downstream of 2 repeat regions (R13/R12) were found. Abundant variations indicate high genetic diversity at the MHC region in indigenous chickens. Rare alleles are vulnerable to genetic drift in small populations, and can be used as molecular markers for monitoring the dynamic conservation of many indigenous breeds. PMID- 24235220 TI - Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs. AB - Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland. PMID- 24235221 TI - Influence of dietary calcium level, calcium source, and phytase on bird performance and mineral digestibility during a natural necrotic enteritis episode. AB - The objective of this study was to determine the influence of Ca source [highly soluble calcified seaweed (HSC) or limestone], phytase supplementation, and dietary levels of Ca on bird performance and mineral digestibility (Ca and P) during a necrotic enteritis (NE) episode. Cobb 500 male broilers were weighed and randomized into 8 treatment groups (9 pens/treatment; 30 birds/pen) at day of hatch. The 21-d trial was designed as a 2 * 2 * 2 factorial, which included 2 dietary levels of Ca (0.6 and 0.9%), 2 Ca sources (limestone or HSC), and 2 levels of an Escherichia coli phytase (0 or 1,000 FTU/kg). One unit of phytase (FTU) is defined as the quantity of enzyme that releases 1 MUmol of inorganic phosphorus/min from 0.00015 mol/L of sodium phytate at pH 5.5 at 37 degrees C. Birds were placed on used litter from a previous flock that exhibited clinical signs of NE. Birds and feed were weighed on d 7, 14, and 21, and BW gain, feed intake, and feed conversion were calculated for each of these periods and cumulatively. Mortality was recorded daily and pH of the gizzard and duodenum were measured on d 7, 14, and 21. Ileal digesta (8 birds/pen) was collected on d 7, 14, and 21. Significance is reported at P < 0.05. Birds began exhibiting clinical signs of NE on d 9, and elevated NE-associated mortality persisted until the end of the trial. Significantly higher mortality was observed when broilers were fed diets with 0.9% Ca from HSC compared with birds fed diets with 0.6% Ca, regardless of Ca source. Broilers fed 0.6% Ca diets supplemented with phytase were heavier than the other treatments regardless of Ca source. Broilers fed diets formulated with HSC had significantly higher feed conversion then broilers fed diets formulated with limestone. The gizzard of broilers fed 0.9% Ca in the diet was significantly less acidic than the gizzard of broilers fed 0.6% Ca in the diet. Broilers fed 0.6% Ca in diets supplemented with phytase showed significant improvements in P and Ca digestibility. In conclusion, higher dietary Ca (0.9% vs. 0.6%) had a negative effect on mortality associated with NE and on bird performance. PMID- 24235222 TI - Effect of Mycoplasma synoviae and lentogenic Newcastle disease virus coinfection on cytokine and chemokine gene expression in chicken embryos. AB - Mycoplasma synoviae and Newcastle disease virus (NDV) are 2 avian pathogens that cause modulation in expression of a variety of cytokine and chemokine genes in chickens. However, there is limited data about gene modulation after coinfection with these 2 pathogens and even less data about gene modulation after infection of chicken embryos. In this study, the effect of M. synoviae type strain WVU 1853 and lentogenic LaSota vaccine strain of NDV infection on cytokine and chemokine gene expression in chicken embryos was analyzed in the liver, spleen, bursa of Fabricius, and thymus by using quantitative real-time PCR. Three types of infection were performed; infection with M. synoviae on d 10, infection with NDV on d 17; and consecutive infection with both pathogens, where M. synoviae was inoculated on d 10 and NDV on d 17. Thus, simulation of consecutive infection that may occur after NDV infection of the M. synoviae-infected host was performed. Mycoplasma synoviae infection of embryos resulted in intensive upregulation of cytokine and chemokine genes, including interferon (IFN)-gamma, IL-1beta, IL-6, IL-12p40, IL-16, IL-18, MIP-1beta (CCL4), inducible nitric oxide synthase (iNOS), XCL1, and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), with different expression profiles in the 4 organs. Inoculation of lentogenic NDV significantly upregulated IFN-gamma, IL-6, and IL-16 genes in spleen and IFN-gamma, IL-1beta, IL-2, IL-16, IL-21, XCL1, and MIP-1beta (CCL4) genes in the thymus, but to a lesser extent than M. synoviae. However, no genes were upregulated by NDV in the liver and bursa of Fabricius. Overall effect of NDV inoculation, regarding the number of modulated cytokine and chemokine genes and the extent of expression, was lower than M. synoviae. When NDV was introduced after on-going M. synoviae infection, most M. synoviae-induced cytokine and chemokine genes were significantly downregulated. This study provides the first evidence in chicken embryos that consecutive infection with NDV could suppress expression of cytokine and chemokine genes being significantly upregulated by the previous M. synoviae infection. PMID- 24235223 TI - Comparison of water-based foam and carbon dioxide gas emergency depopulation methods of turkeys. AB - Recommended response strategies for outbreaks of avian influenza and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. The best methods of emergency mass depopulation should maximize human health and safety while minimizing disease spread and animal welfare concerns. The goal of this project was to evaluate the effectiveness of 2 mass depopulation methods on adult tom turkeys. The methods tested were carbon dioxide gassing and water-based foam. The time to unconsciousness, motion cessation, brain death, and altered terminal cardiac activity were recorded for each bird through the use of an electroencephalogram, accelerometer, and electrocardiogram. Critical times for physiological events were extracted from sensor data and compiled in a spreadsheet for statistical analysis. A statistically significant difference was observed in time to brain death, with water-based foam resulting in faster brain death (u = 190 s) than CO2 gas (u = 242 s). Though not statistically significant, differences were found comparing the time to unconsciousness (foam: u = 64 s; CO2 gas: u = 90 s), motion cessation (foam: u = 182 s; CO2 gas: u = 153 s), and altered terminal cardiac activity (foam: u = 208 s; CO2 gas u = 242 s) between foam and CO2 depopulation treatments. The results of this study demonstrate that water-based foam can be used to effectively depopulate market size male turkeys. PMID- 24235224 TI - Acquisition of immunity to the protozoan parasite Eimeria adenoeides in turkey poults and cellular responses to infection. AB - Newly hatched turkey poults were infected with 10(2) oocysts of Eimeria adenoeides and subsequently reinfected with 10(3) and 10(4) oocysts at 6 and 12 d of age, respectively. Three peaks in oocyst production were observed in the feces of poults following this series of infections. A second group of poults given the same dosing regimen was challenged with 5 * 10(4) oocysts/poult at different times to evaluate the acquisition of immunity. Judging by weight gain and mortality, no protection had been acquired at 6 d of age, but partial protection was observed by 12 and 18 d of age. A third group of poults were also infected with 10(2) oocysts and subsequently reinfected with 10(3) and 10(4) oocysts at 6 and 12 d of age to evaluate cellular immune responses to infection. Sections of ceca from infected poults showed a significantly higher leukocyte infiltration on d 6, 10, 12, 16, and 18 after infection than uninfected controls. The percent area occupied by CD4+ and CD8+ lymphocytes in the ceca, as assessed by immunohistochemistry, was significantly elevated in infected poults on d 12, 16, and 18. The relative expression of chemokine CXCLi2, and cytokines IL1beta, IFNgamma, IL10, IL13, IL2, IL12b, and IL18 was measured by real-time reverse transcription PCR. The expression of CXCLi2 and IL10 was found to be elevated on d 12, and IFNgamma on d 10, 12, and 16. Expression of IL13 and IL18 was increased on d 10 and IL2 on d 10 and 16, and that of IL12b on d 16 in infected poults. Increase in the infiltration of leukocytes, percent area occupied by CD4+ and CD8+ lymphocytes, and changes in the relative expression of cytokines in the ceca characterize the dynamics of immune responses in turkey poults infected with E. adenoeides early in life. PMID- 24235225 TI - Pharmacokinetic/pharmacodynamic evaluation of the efficacy of flumequine in treating colibacillosis in turkeys. AB - Flumequine (FLU) is used in the treatment of systemic bacterial infections in poultry, including colibacillosis, which is a common disease in turkeys. The pharmacokinetic (PK) behavior of FLU administered to 32 healthy turkeys as an oral bolus via gavage or as 10-h pulsed administration in drinking water were compared, using the authorized dose of 15 mg/kg and the double dose of 30 mg/kg. The minimum inhibitory concentrations (MIC) of 235 Escherichia coli field strains isolated from poultry were determined for pharmacodynamics (PD) to develop a PK/PD model. Blood samples were collected at established times over 24 h, and the obtained plasma was analyzed using a liquid chromatography tandem mass spectrometry method that was validated in-house. A monocompartmental model and a noncompartmental model were applied to the data to obtain the PK results. For both types of administration and both dosages, the ratios of the maximum concentration (Cmax)/MIC50 and the area under the plasma concentration-time curve (AUC)/MIC50 achieved were considerably lower than the fluoroquinolone breakpoints usually adopted for efficacy. The Cmax/MIC50 and AUC0-24/MIC50 ratios were, respectively, 0.67 +/- 0.09 and 4.76 +/- 0.48 and 1.18 +/- 0.35 and 7.05 +/- 2.40 for the 15 and 30 mg/kg bolus doses, respectively. After 10-h pulsed administration of 15 mg/kg, values of Cmax/MIC50, 0.19 +/- 0.02 on d 1 and 0.30 +/- 0.08 on d 5 of therapy were obtained, the AUC/MIC50 ratios were 2.09 +/- 0.29 and 3.22 +/- 0.93 on d 1 and 5, respectively. Higher values were obtained with the doubled dose of 30 mg/kg: the Cmax/MIC50 ratios were 0.49 +/- 0.11 on d 1 and 0.69 +/- 0.18 on d 5; the AUC/MIC50 ratios were 5.15 +/- 1.15 and 6.57 +/- 1.92 on d 1 and 5, respectively. Based on these results, FLU administration should be adopted when specific diagnostic findings indicate its efficacy, and revising the dosage scheme to comply with the prudent and responsible use of antimicrobials in veterinary medicine is advisable. PMID- 24235226 TI - A 5-year retrospective report of Gallibacterium anatis and Pasteurella multocida isolates from chickens in Mississippi. AB - A 5-yr retrospective study (November 2006-December 2011) was conducted to determine the isolation frequency of Pasteurella multocida and Gallibacterium anatis and their antibiograms from chickens submitted to the Mississippi Poultry Research and Diagnostic Laboratory. The number of isolations of G. anatis increased over the last 5 yr in broiler and broiler breeder type chickens. For P. multocida, the number of isolations increased from 2006 to 2010, but decreased through 2011 with all isolations being from boiler breeder type chickens. Gallibacterium anatis demonstrated almost complete resistance to novobiocin, tylosin, lincosamide, and tetracycline antimicrobials with moderate to high sensitivity to sulfonamides, fluoroquinolones, and florfenicol. There was intermediate sensitivity for spectinomycin and erythromycin and variable resistance to beta-lactam and aminoglycoside antimicrobials. In sharp contrast, P. multocida showed moderate to high sensitivity to beta-lactam, novobiocin, and tetracycline antimicrobials, but had antibiograms similar to G. anatis for the other antimicrobials. Sensitivities were determined using minimum inhibitory concentration. This study examines the trends over a 5-yr period of the number of isolates of P. multocida and G. anatis and their sensitivities. These 2 pathogens produce very similar clinical signs and lesions (fowl cholera-like) in breeders despite having extremely antagonistic sensitivity patterns. This study shows the necessity for producers to attempt culture and sensitivity in suspect fowl cholera-like flocks before initiating antimicrobial treatment commonly used with P. multocida for fear that the culprit may actually be the more antimicrobial resistant G. anatis. PMID- 24235227 TI - Impact of fowlpox-vectored Mycoplasma gallisepticum vaccine Vectormune FP MG on layer hen egg production and egg quality parameters. AB - This study was conducted to determine the impact of vaccination with Vectormune FP MG on egg production and egg quality characteristics of Single Comb White Leghorn hens. Due to questions of the efficacy of this vaccine in preventing Mycoplasma gallisepticum-mediated pathology, the ability of this vaccine to protect against postproduction-peak egg losses associated with F-strain M. gallisepticum (FMG) vaccination was also investigated. Vaccination with Vectormune FP MG did not result in any significant change in egg production or egg quality parameters compared with control (unvaccinated) hens. Subsequent revaccination with FMG at 45 wk of age (woa) yielded no impact on egg production or egg quality parameters of Vectormune FP MG vaccinated hens, unlike prior results for postproduction-peak vaccination of M. gallisepticum-clean hens with FMG, which exhibited a drop in egg production of approximately 6%. No difference in egg size distribution was observed for any of the treatment groups before or after FMG revaccination. These results suggest that hens can be safely vaccinated with Vectormune FP MG as pullets and can be revaccinated with a live M. gallisepticum vaccine such as FMG at a later date with no deleterious effects on egg production or egg or eggshell quality parameters. PMID- 24235228 TI - Apparent metabolizable energy and prediction equations for reduced-oil corn distillers dried grains with solubles in broiler chicks from 10 to 18 days of age. AB - An experiment consisting of 2 identically designed trials was conducted to determine the nutrient composition and AMEn content of distillers dried grains with solubles (DDGS) to develop prediction equations for AMEn in broilers. Fifteen samples of DDGS ranging in ether extract (EE) from 3.15 to 13.23% (DM basis) were collected from various dry-grind ethanol plants and were subsequently fed to broiler chicks to determine AMEn content. A corn-soybean meal control diet was formulated to contain 15% dextrose, and test diets were created by mixing the control diet with 15% DDGS at the expense of dextrose. In each trial, 672 male Ross * Ross 708 chicks were housed in grower battery cages with 7 birds per cage (0.06 m(2)/bird) and received a common starter diet until 10 d of age. Each cage was randomly assigned to 1 of 16 dietary treatments, with 6 replicate pens per treatment. Experimental diets were fed over a 6-d acclimation period from 10 to 16 d of age, followed by a 48-h total excreta collection period. Gross energy (GE) and CP of the experimental diets and excreta were determined to calculate AMEn for each DDGS sample. On a DM basis, AMEn of the 15 DDGS samples ranged from 1,869 to 2,824 kcal/kg. Analyses were conducted to determine the GE, CP, EE, DM, starch, total dietary fiber (TDF), neutral detergent fiber (NDF), acid detergent fiber (ADF), and ash content of the DDGS samples. Stepwise regression resulted in the following best-fit equation for AMEn (DM basis) based on the adjusted coefficient of determination (R(2)adj), SE, and prediction error sum of squares (PRESS): AMEn, kcal/kg = -12,282 + (2.60 * GE) + (89.75 * CP) + (125.80 * starch) - (40.67 * TDF; R(2)adj = 0.86; SE = 98.76; PRESS = 199,819; P <= 0.001). These results indicated that the composition of DDGS with variable EE content may be used to predict AMEn in broiler chicks. PMID- 24235229 TI - Assessing the age-dependent optimal dietary branched-chain amino acid ratio in growing chicken by application of a nonlinear modeling procedure. AB - Based on a nonlinear N utilization model, 2 N balance experiments with growing broiler chickens were conducted, investigating the ideal amino acid (AA) ratio (IAAR) of the branched-chain AA (BCAA) Leu, Ile, and Val related to Lys. In both of the experiments, the starter (I: 10-20 d of age) and grower periods (II: 25-35 d of age) utilized 36 male Ross 308 chickens each (n = 144). Nitrogen balance periods were divided into an adaptation period (5 d) and 2 consecutive collection periods (2 * 5 d). Diets of experiment 1 were based on a consistent mixture of wheat, soy protein concentrate, wheat gluten, fish meal, and crystalline AA, subsequently diluted by wheat starch to provide 8 graded CP levels (6-34% CP). Results of nonlinear regression between N intake and N deposition yielded the theoretical maximum for N deposition (NDmaxT; I: 4,593 mg of N/BWkg(0.67)/d; II: 4,302 mg of N/BWkg(0.67)/d). Furthermore, the daily N maintenance requirement (NMR) was derived (I: 113 mg of N/BWkg(0.67); II: 215 mg of N/BWkg(0.67)/d). Both the age-dependent data for NMR and NDmaxT were applied to calculate the model parameter b (protein quality, independent of N intake) and bc(-1) (efficiency of limiting AA), respectively. Five diets based on the same ingredients as in experiment 1 were formulated for experiment 2: an AA balanced basal diet and 4 diets of the same composition but lacking in supply of Lys, Leu, Ile, or Val. All experimental diets were isocaloric and isonitrogenous. For calculation of the IAAR, observed bc(-1) data of each AA diluted diet were utilized. The concluded IAAR of Lys:Leu:Ile:Val for the starter and grower period were 100:94:55:65 and 100:106:56:72, respectively. These results indicated a higher demand for Leu and Val during the grower phase and, generally, a lower IAAR for the BCAA than previously reported in comparable experiments. PMID- 24235230 TI - Effects of dietary tryptophan on protein metabolism and related gene expression in Yangzhou goslings under different feeding regimens. AB - This study was conducted to investigate the effects of feeding regimens and dietary Trp levels on protein metabolism and regulation of the related gene expression in Yangzhou goslings. A 2 * 3 factorial completely randomized experiment was applied, and the treatments were designed as 2 feeding regimens (ad libitum vs. restricted feeding), and each contained 3 levels of Trp (low-Trp group, 0.14%; medium-Trp group, 0.22%; high-Trp group, 0.30%). The results show that ADG and feed conversion ratio (FCR) were significantly affected by feeding regimens (P < 0.05); dietary Trp levels influenced ADG and ADFI in the starter and overall period (P < 0.05), and interactions between Trp levels and feeding regimens on ADG, ADFI, and FCR were observed in different growing periods (P < 0.05). Serum total protein, triglycerides, and total cholesterol levels in the ad libitum group were higher than those in the restricted feeding group (P < 0.05), and the concentration of serum total protein, glucose, and insulin-like growth factor-I were higher in the medium-Trp and high-Trp groups (P < 0.05); however, serum uric acid, triglyceride, and cortisol levels were reduced in the high-Trp group (P < 0.05). Feeding regimen and dietary Trp levels affected serum glucose (P < 0.05) interactively. In the ad libitum group, tryptophanyl tRNA synthetase (TTS) mRNA expressed at a higher level in the high-Trp treatment, whereas expression of poultry target of rapamycin (pTOR) and p70 ribosomal protein S6 kinase1 (S6K1) mRNA was upregulated in the low-Trp treatment (P < 0.05). Expression and phosphorylation levels of pTOR were upregulated in thigh tissue with increased dietary Trp, but cathepsin B and 20S protease mRNA expression decreased (P < 0.05). It was concluded that the protein deposition in gosling thigh tissue was affected by dietary Trp through positive regulation of the TTS mRNA and pTOR protein expression and phosphorylation levels for protein synthesis, as well as the suppression of protein degradation-related gene expression. PMID- 24235231 TI - Induction of mucin expression by estrogen and lipopolysaccharide in the lower oviductal segments in hens. AB - Mucins play an essential role as mucosal barrier to prevent invasion of pathogens in the oviductal tissue of hens. The aim of this study was to determine the effect of estradiol and lipopolysaccharide (LPS) on the mucin expression in the lower oviductal segments (vagina and uterus) of hens. The mucosal tissues of the vagina and uterus were collected from White Leghorn laying and molting hens, and molting hens with or without intramuscular injection with 1 mg of estradiol benzoate (EB) daily for 7 d. Part of these tissues was cultured in TCM-199 culture medium with or without LPS (10, 100, or 1,000 ng/mL) for 1.5 or 3 h. Mucin expression in the mucosa of laying, molting, and EB-treated molting hens (EB-group) and in those tissues cultured with or without LPS was analyzed by quantitative reverse-transcription PCR. Cultured tissues were also processed for paraffin sections and stained with Alcian blue (AB). In both the vagina and uterus, mucin expression and density of AB-positive mucopolysaccharide were reduced in molting hens compared with laying hens, and upregulated by EB. Mucin expression in the cultured vagina and uterus tissues of laying and molting hens was upregulated by LPS in a dose- and time-dependent manner. However, there was no response to LPS for induction of mucin in the tissues of EB-group hens. The mucin expression level in the vagina and uterus tissues stimulated by LPS was lower in the EB-group hens than in laying and molting hens, and that in the uterus was lower in the molting hens than in laying hens. These results suggest that mucin expression is stimulated by LPS in the vagina and uterus of laying and molting hens. Estrogen may upregulate mucin expression in those tissues in association with epithelial development, whereas it may suppress the response to LPS for mucin induction. The mucin expression caused by LPS may enhance mucosal barrier function and play a role in preventing infections by bacteria in the vagina and uterus. PMID- 24235232 TI - Expression and identification of recombinant chicken vascular endothelial growth factor in Pichia pastoris and its role in the pathogenesis of tibial dyschondroplasia. AB - Vascular endothelial growth factor (VEGF) is an essential mediator of angiogenesis and endochondral ossification. To explore the role of VEGF in avian diseases such as tibial dyschondroplasia (TD), a typical disorder of endochondral ossification, we expressed and identified recombinant chicken VEGF (chVEGF) protein in Pichia pastoris and evaluated its effects on thiram-induced TD in broiler chickens. The SDS-PAGE showed that 2 recombinant proteins, with molecular weights of ~46 and ~70 kDa, were obtained. Western blot analysis indicated that the 2 proteins were recognized by rabbit anti-chicken and goat anti-human VEGF polyclonal antibodies. Moreover, the mixture of the proteins significantly stimulated angiogenesis in the chick chorioallantoic membrane. In 21-d-old broilers that had been fed a thiram-enriched diet (100 mg/kg of thiram for 2 d at 8 d old) to induce TD, intramuscular injection of the chVEGF proteins (at a dosage of 10 or 30 MUg/kg) significantly reduced the severity of TD but had no effect on TD incidence or BW; decreased serum Ca and P concentrations and tartrate-resistant acid phosphatase activity and elevated serum alkaline phosphatase activity; enhanced the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase activities in the liver and kidney; upregulated the expression of type X collagen, matrix metalloproteinase (MMP)-13, and Runx2; and downregulated the Bcl-2 expression in the growth plates. In thiram treated broilers at 15 d old, the chVEGF proteins upregulated the expression of MMP-13 and Runx2, and had different effects on type X collagen and Bcl-2 expression at different dosages. Our results indicate that exogenous chVEGF proteins promoted the recovery of TD-affected growth plates by improving the antioxidant capacity in the liver and kidney and by regulating differential expression of genes relating to endochondral ossification at different stages of TD development; VEGF deficiency in the growth plates was involved in the pathogenesis of TD. PMID- 24235233 TI - Rapid inactivation of Salmonella Enteritidis on shell eggs by plant-derived antimicrobials. AB - Salmonella Enteritidis is a common foodborne pathogen transmitted to humans largely by consumption of contaminated eggs. The external surface of eggs becomes contaminated with Salmonella Enteritidis from various sources on farms, the main sources being hens' droppings and contaminated litter. Therefore, effective egg surface disinfection is critical to reduce pathogens on eggs and potentially control egg-borne disease outbreaks. This study investigated the efficacy of GRAS (generally recognized as safe) status, plant-derived antimicrobials (PDA), namely trans-cinnamaldehyde (TC), carvacrol (CR), and eugenol (EUG), as an antimicrobial wash for rapidly killing Salmonella Enteritidis on shell eggs in the presence or absence of chicken droppings. White-shelled eggs inoculated with a 5-strain mixture of nalidixic acid (NA) resistant Salmonella Enteritidis (8.0 log cfu/mL) were washed in sterile deionized water containing each PDA (0.0, 0.25, 0.5, or 0.75%) or chlorine (200 mg/kg) at 32 or 42 degrees C for 30 s, 3 min, or 5 min. Approximately 6.0 log cfu/mL of Salmonella Enteritidis was recovered from inoculated and unwashed eggs. The wash water control and chlorine control decreased Salmonella Enteritidis on eggs by only 2.0 log cfu/mL even after washing for 5 min. The PDA were highly effective in killing Salmonella Enteritidis on eggs compared with controls (P < 0.05). All treatments containing CR and EUG reduced Salmonella Enteritidis to undetectable levels as rapidly as within 30 s of washing, whereas TC (0.75%) completely inactivated Salmonella Enteritidis on eggs washed at 42 degrees C for 30 s (P < 0.05). No Salmonella Enteritidis was detected in any PDA or chlorine wash solution; however, substantial pathogen populations (~4.0 log cfu/mL) survived in the antibacterial free control wash water (P < 0.05). The CR and EUG were also able to eliminate Salmonella Enteritidis on eggs to undetectable levels in the presence of 3% chicken droppings at 32 degrees C (P < 0.05). This study demonstrates that PDA could effectively be used as a wash treatment to reduce Salmonella Enteritidis on shell eggs. Sensory and quality studies of PDA-washed eggs need to be conducted before recommending their use. PMID- 24235234 TI - SavorPhos as an all-natural phosphate replacer in water- and oil-based marinades for rotisserie birds and boneless-skinless breast. AB - As consumer demand for all-natural marinades increases, the need to replace phosphate with a natural product that can produce equivalent or improved yield in products such as but not limited to rotisserie chickens (whole birds without giblets) and boneless/skinless breast (BSB) is a challenge for processors. The objective of this study was to determine if using an all-natural nonphosphate blend (SavorPhos-200, SP) in water-based (WB) and oil-based (OB) marinades would perform better than a commercial phosphate blend (PB). The treatments included WB+PB (water, 0.4% phosphate, 0.7% salt), WB+SP (water, 0.5% SavorPhos-200, 0.7% salt), OB+PB (water, 3% oil, 0.4% phosphate, 0.7% salt), and OB+SP (water, 3% oil, 0.5% SavorPhos-200, 0.7% salt). The rotisserie chickens and BSB were injected with a multineedle injector to 20% (wt/wt) pickup at a constant pressure (103-138 kPa). The parameters measured were marinade pickup %, 20-min and 24-h marinade retention %, and cook loss %. Color, tenderness, total moisture, and sensory test were conducted on BSB. Data were analyzed within marinade type (WB and OB). Rotisserie birds picked up and retained the same yield in WB marinades. In OB marinades, SP had higher yields postinjection and lower cook loss % than the PB, while retaining the same yield over 24 h. For BSB, the cook loss was lower in SP than the PB in WB marinades. Higher yields postinjection were achieved with OB, but had the same retention 20 min and 24 h postinjection and cook loss % as the PB. No differences were observed for total moisture or L* (lightness) within marinade type and treatment. Texture was lower, indicating increased tenderness (P < 0.05) on SP samples in both marinades. However, consumers were not able to distinguish between treatments in sensory analyses. Therefore, SavorPhos-200 can be used as a natural nonphosphate blend in WB marinades with no detriment to yield. In addition, SavorPhos-200 can be used as a natural nonphosphate blend in OB marinades with yield improvements. PMID- 24235235 TI - Evaluation of the antioxidant effect of ganghwayakssuk (Artemisia princeps Pamp.) extract alone and in combination with ascorbic acid in raw chicken patties. AB - We investigated the inhibition of lipid oxidation of raw chicken patties by the antioxidants ascorbic acid (Aa), ganghwayakssuk extracts (GE), and their combination (Aa + GE). All antioxidant combinations were effective at delaying lipid oxidation compared with the control or Aa. A combination of Aa + GE (0.05% Aa + 0.2% GE) was the most effective for delaying lipid oxidation (TBA reactive substances, conjugated dienes, and peroxide formation). The color values of all samples were significantly affected by adding GE. Additionally, the redness, color difference, and hue values of all treatments, except for Aa, were lower than those of the control as the amount of GE increased. The total viable bacterial counts of samples with GE 0.2 and Aa + GE 0.2 were significantly affected during storage (P < 0.05). The results suggest that adding an antioxidant combination reduced the oxidative stress and microbial growth of raw chicken patties stored for 12 d under normal refrigeration temperature, which may extend the shelf life of chicken patties. PMID- 24235236 TI - The development of chlorophyll-based markers in poultry diets to aid detection of fluorescent fecal contamination. AB - Incidents of foodborne illness associated with consuming undercooked or raw chicken are often linked to 2 causative pathogens: Campylobacter spp. or Salmonella spp. Numerous studies have shown that contamination of carcasses results when pathogens are transferred from the intestinal tract or fecal material on feet and feathers to the dressed carcass. Ultraviolet spectral imaging to detect surface fecal and ingesta contamination on poultry carcasses may provide a solution to aid detection. However, poultry diets do not provide sufficiently high levels of natural fluorophores for this system to be reliable. This study investigated the potential of chlorophyll-based feed additives to improve fluorescence of the feces and narrow the excitation and emission wavelengths to aid in the development of a simple visualization system. Twenty four hens (Gallus gallus domesticus) were allocated at random to 1 of 4 treatments: control (C, no marker), Zn chlorophyllin, Mg chlorophyllin, or Fe chlorophyllin. All markers were incorporated into mash before pelleting at a rate of 1 g/kg of DM. The experiment consisted of two 4 * 4 Latin squares with each period consisting of 2 wk. Feces were collected and extracted in acetone:water (50:50; vol/vol) with fecal fluorescence emission spectra determined using a Jasco FP-6200 Spectrofluorometer with excitation at 382 nm. A main peak evolved at wavelength 670 nm with the total area under the peak used as fluorescence intensity. Following 7 d of marker supplementation, the 3 markers improved the fluorescence intensity by *14.8, 12.8, and 6.9 for Fe, Mg, and Zn chlorophyllin, respectively, compared with the control. The addition of feces containing Mg chlorophyllin to chicken carcass increased detection of the feces compared with feces with no marker. Also, due to the plain background of chicken skin, a simple image at 675 nm with appropriate thresholds would allow detection of contaminated carcasses at the current slaughter line speed without the need of expensive hyperspectral imaging. PMID- 24235237 TI - Comparison of fatty acid, cholesterol, vitamin A and E composition, and trans fats in eggs from brown and white egg strains that were molted or nonmolted. AB - The impact of egg color, hen strain, and molting on the nutritional composition of eggs is limited. Therefore, this study compared nutritional composition and component percentages of cage-produced shell eggs with respect to egg color, hen strain, and molt. Four strains were selected from the North Carolina Layer Performance and Management Test: Hy-Line Brown (HB) and Bovans Brown (BB), and Hy Line W-36 (HW) and Bovans White (BovW) were selected. Two groups from each strain were selected and 2 groups of molted HW and BovW were selected and compared with their nonmolted counterparts to examine the molt's impact. Two sets of eggs from each replicate were collected simultaneously at 101 wk of age. One sample of eggs was broken into a 12-egg pool stomached for 3 min (n = 12 samples), then divided into six 50-mL tubes, sealed, and frozen to be sent for cholesterol, n-3 fatty acids, saturated fat, monounsaturated fats, polyunsaturated fats, beta-carotene, vitamin A, and vitamin E analyses. The other set of 12 eggs was then assessed for component percentages. The HW eggs had a greater (P < 0.05) percentage of yolk than the BovW eggs of 28.12 versus 27.00%, respectively; however, the BovW eggs had 1.0% more albumen. The HB and BB egg components were not different. Brown eggs were heavier (P < 0.01) than white eggs. White eggs had greater (P < 0.0001) percent yolk and the brown eggs had greater (P < 0.0001) percent albumen. The eggs from molted hens had a greater (P < 0.001) percent shell. Total fat content in the samples was (P < 0.05) higher in white eggs by 0.70% than brown eggs due to increased saturated and polyunsaturated fats. The molting of hens reduced (P < 0.01) saturated fats by 0.21% in the egg. Vitamin A levels were higher (P < 0.0001) in white eggs, and vitamin E was higher (P < 0.0001) in brown eggs. Strain and molt appear to influence nutrient composition and component percentages in eggs produced from laying hens. PMID- 24235238 TI - Comparison of a novel strategy for the detection and isolation of Salmonella in shell eggs with the Food and Drug Administration Bacteriological Analytical Manual method. AB - The current FDA Bacteriological Analytical Manual (BAM) method for the detection of Salmonella in eggs requires 2 wk to complete. The objective of this project was to improve the BAM method for the detection and isolation of Salmonella in whole shell eggs. A novel protocol, using 1,000 g of liquid eggs for direct preenrichment with 2 L of tryptic soy broth (TSB) followed by enrichment using Rappaport-Vassiliadis and Tetrathionate broths, was compared with the standard BAM method, which requires 96 h room temperature incubation of whole shell egg samples followed by preenrichment in TSB supplemented with FeSO4. Four Salmonella ser. Enteritidis (4 phage types) and one Salmonella ser. Heidelberg isolates were used in the study. Bulk inoculated pooled liquid eggs, weighing 52 or 56 kg (approximately 1,100 eggs) were used in each trial. Twenty 1,000-g test portions were withdrawn from the pooled eggs for both the alternative and the reference methods. Test portions were inoculated with Salmonella at 1 to 5 cfu/1,000 g eggs. Two replicates were performed for each isolate. In the 8 trials conducted with Salmonella ser. Enteritidis, the alternative method was significantly (P < 0.05) more productive than the reference method in 3 trials, and significantly (P < 0.05) less productive than the reference method in 1 trial. There were no significant (P < 0.05) differences between the 2 methods for the other 4 trials. For Salmonella ser. Heidelberg, combined data from 2 trials showed the alternative method was significantly (P < 0.05) more efficient than the BAM method. We have concluded that the alternative method, described herein, has the potential to replace the current BAM culture method for detection and isolation of Salmonella from shell eggs based on the following factors: 1) the alternative method is 4 d shorter than the reference method; 2) it uses regular TSB instead of the more complicated TSB supplemented with FeSO4; and 3) it was equivalent or superior to the reference method in 9 out of 10 trials for the detection of Salmonella in shell eggs. PMID- 24235239 TI - Carnosine, anserine, creatine, and inosine 5'-monophosphate contents in breast and thigh meats from 5 lines of Korean native chicken. AB - The aim of this study was to examine the effect of chicken line on the contents of endogenous compounds, including carnosine, anserine, creatine, and inosine 5' monophosphate (IMP), in breast and thigh meats from 5 lines of Korean native chicken for the development of high-quality meat breeds. Additionally, the effects of sex (male or female) and meat type (breast or thigh meat) were examined. In total, 595 F1 progeny [black: 90 (male: 45, female: 45); gray-brown: 110 (male: 52, female: 58); red-brown: 136 (male: 68, female: 68); white: 126 (male: 63, female: 63); and yellow-brown: 133 (male: 62, female: 71)] from 70 full-sib families were used. The male chicken from the red-brown line and the female chicken from the black line showed the highest BW among the 5 lines. Carnosine content was higher in female chicken and breast meat than in male chicken and thigh meat, respectively. Breast meat contained higher anserine content compared with thigh meat. The sex effect on anserine was not consistent between breast and thigh meat. Creatine content was not consistently influenced by sex between breast and thigh meat, and no meat type effect was observed. The IMP contents were higher in female chicken and breast meat compared with male chicken and thigh meat, respectively. In addition, we clearly observed line effects by the comparison of the contents of carnosine, anserine, creatine, and IMP for each meat type according to each sex. These data are useful for selection and development of high-quality, meat-type chicken breeds. PMID- 24235240 TI - The effect of season, sex, and portion on the carcass characteristics, pH, color, and proximate composition of Egyptian Goose (Alopochen aegyptiacus) meat. AB - The carcass yield, physical characteristics, and proximate composition of Egyptian geese (Alopochen aegyptiacus), a southern African gamebird species, have been studied. A total of 69 geese were harvested during 2 seasons: summer (n = 36) and winter (n = 33). This total group of geese consisted of 27 female birds and 42 male birds. Sex alone affected (P <= 0.05) the live and carcass weights, and the average muscle weight (g) of each portion was higher for the male fowl. The data does not indicate differences between the meat's physical characteristics on account of sex; however, the meat from the female birds did have a higher intramuscular fat content. Season (winter vs. summer) did not influence the average muscle weights (g) of the breast, thigh, and drumstick portions, but the intramuscular fat content content of the birds hunted in winter was higher. Muscle color and pH differed as a result of season with the summer meat having a higher pH and more vivid red color compared with winter. The physical characteristics and the proximate composition of the breast, thigh, and drumstick portions varied considerably. This is essentially connected to a difference in physical activity of the muscles in the portions. Overall, this study revealed that to ensure a consistent eating quality the harvesting periods of Egyptian geese should be considered. PMID- 24235241 TI - Egg white proteins and their potential use in food processing or as nutraceutical and pharmaceutical agents--a review. AB - Egg white contains many functionally important proteins. Ovalbumin (54%), ovotransferrin (12%), ovomucoid (11%), ovomucin (3.5%), and lysozyme (3.5%) are among the major proteins that have high potentials for industrial applications if separated. The separation methods for these proteins from egg white have been developed since early 1900, but preparation methods of these proteins for commercial applications are still under development. Simplicity and scalability of the methods, use of nontoxic chemicals for the separation, and sequential separation for multiple proteins are very important criteria for the commercial production and application of these proteins. The separated proteins can be used in food and pharmaceutical industry as is or after modifications with enzymes. Ovotransferrin is used as a metal transporter, antimicrobial, or anticancer agent, whereas lysozyme is mainly used as a food preservative. Ovalbumin is widely used as a nutrient supplement and ovomucin as a tumor suppression agent. Ovomucoid is the major egg allergen but can inhibit the growth of tumors, and thus can be used as an anticancer agent. Hydrolyzed peptides from these proteins showed very good angiotensin I converting enzyme inhibitory, anticancer, metal binding, and antioxidant activities. Therefore, separation of egg white proteins and the productions of bioactive peptides from egg white proteins are emerging areas with many new applications. PMID- 24235242 TI - Effect of transportation duration of 1-day-old chicks on postplacement production performances and pododermatitis of broilers up to slaughter age. AB - This experiment studied the effect of transportation duration of 1-d-old chicks on dehydration, mortality, production performance, and pododermatitis during the growout period. Eggs from the same breeder flock (Ross PM3) were collected at 35, 45, and 56 wk of age, for 3 successive identical experiments. In each experiment, newly hatched chicks received 1 of 3 transportation duration treatments from the hatchery before placement in the on-site rearing facility: no transportation corresponding to direct placement in less than 5 min (T00), or 4 (T04) or 10 h (T10) of transportation. The chicks were housed in 35-m(2) pens (650 birds each) and reared until 35 d old. Hematocrit and chick BW were measured on sample chicks before and after transportation. During the growout period, bird weight, feed uptake, and feed conversion ratio were measured weekly until slaughter. Transportation duration affected BW; T00 groups had a significantly higher BW than T04 and T10 transported birds but this effect lasted only until d 21. No clear effect on hematocrit, feed uptake, feed conversion ratio, or mortality was observed for birds transported up to 10 h. The decrease in weight in T10 birds was associated with less severe pododermatitis. Increasing age of the breeder flock was correlated with reduced egg fertility and hatchability, and also with higher quality and BW of hatched chicks. Chicks from older breeders also exhibited reduced mortality during the growout period. PMID- 24235243 TI - Effects of preincubation heating of broiler hatching eggs during storage, flock age, and length of storage period on hatchability. AB - The effects of heating of eggs during storage, broiler breeder age, and length of egg storage on hatchability of fertile eggs were examined in this study. Eggs were collected from Ross 344 male * Ross 308 broiler breeders on paper flats, held overnight (1 d) at 18 degrees C and 75% RH, and then transferred to plastic trays. In experiment 1, eggs were obtained at 28, 38, and 53 wk of flock age. During a further 10 d of storage, eggs either remained in the storage room (control) or were subjected to a heat treatment regimen of 26 degrees C for 2 h, 37.8 degrees C for 3 h, and 26 degrees C for 2 h in a setter at d 5 of storage. In experiment 2, eggs from a flock at 28 wk of age were heated for 1 d of a 6-d storage period. Eggs from a 29-wk-old flock were either heated at d 1 or 5 of an 11-d storage period in experiment 3. In experiment 4, 27-wk-old flock eggs were heated twice at d 1 and 5 of an 11-d storage period. Control eggs stored for 6 or 11 d were coincubated as appropriate in each experiment. Heating eggs at d 5 of an 11-d storage period increased hatchability in experiment 1. Although no benefit of heating 28-wk-old flock eggs during 6 d of storage in experiment 2 was observed, heating eggs from a 29-wk-old flock at d 1 or 5 of an 11-d storage period increased hatchability in experiment 3. Further, heating eggs from a 27-wk old flock twice during 11 d of storage increased hatchability in experiment 4. These effects were probably due to the fact that eggs from younger flocks had been reported to have many embryos at a stage of development where the hypoblast had not yet fully developed (less than EG-K12 to EG-K13), such that heating during extended storage advanced these embryos to a more resistant stage. PMID- 24235244 TI - Mid-term financial impact of animal welfare improvements in Dutch broiler production. AB - This study used a stochastic bioeconomic simulation model to simulate the business and financial risk of different broiler production systems over a 5-yr period. Simulation analysis was conducted using the @Risk add-in in MS Excel. To compare the impact of different production systems on economic feasibility, 2 cases were considered. The first case focused on the economic feasibility of a completely new system, whereas the second examined economic feasibilities when a farm switches from a conventional to an animal welfare-improving production system. A sensitivity analysis was conducted to assess the key drivers of economic feasibility and to reveal systematic differences across production systems. The study shows that economic feasibility of systems with improved animal welfare predominantly depends on the price that farmers receive. Moreover, the study demonstrates the importance of the level and variation of the price premium for improved welfare, particularly in the first 5 yr after conversion. The economic feasibility of the production system increases with the level of welfare improvements for a sufficiently high price level for broiler meat and low volatility in producer prices. If this is not the case, however, risk attitudes of farmers become important as well as the use of potential risk management instruments. PMID- 24235245 TI - Effects of prestorage application of propolis and storage time on eggshell microbial activity, hatchability, and chick performance in Japanese quail (Coturnix coturnix japonica) eggs. AB - Propolis, a resinous mixture produced by honeybees from substances collected from plants, has strong antibacterial and antifungal properties. The purpose of the current study was to establish the effects of prestorage application of propolis and storage time on eggshell microbial activity, egg weight loss, hatchability, and chick performance in quail hatching eggs. Treatments were compared in a 2 * 5 factorial design with 2 different storage times (7 and 14 d) and 5 prestorage applications (control, ethyl alcohol 70%, 5% propolis, 10% propolis, and 15% propolis solution). After application, the eggs were stored for 7 or 14 d at 13 degrees C and 75 to 80% RH before incubation. Eggs sprayed with propolis had lower levels of total aerobic mesophilic bacteria, coliform, Salmonella spp., Staphylococcus spp., and mold yeasts than control eggs over the storage period and incubation period. Microbial activity in eggs stored for 7 d was significantly higher than in eggs stored for 14 d at the end of the storage. The lowest egg weight loss during storage was obtained in P15 treatment eggs stored for 7 d, whereas the highest egg weight loss was found in the treatment A after storage for 14 d. Although propolis treatment at 3 different doses was not effective on relative growth, only P15 decreased the BW at d 10, compared with the control. Hatchability in eggs stored for 14 d was significantly lower than in eggs stored for 7 d. No significant differences were observed for hatchability and embryonic mortality among propolis treatment groups. Propolis did not have a detrimental effect on hatchability, embryonic mortality, or BW gain. Our results indicate that propolis may be used to effectively reduce microbial activity on the surface of quail hatching eggs during storage and incubation without any detrimental effects on hatchability. PMID- 24235246 TI - Optimal procedure planning and guidance system for peripheral bronchoscopy. AB - With the development of multidetector computed-tomography (MDCT) scanners and ultrathin bronchoscopes, the use of bronchoscopy for diagnosing peripheral lung cancer nodules is becoming a viable option. The work flow for assessing lung cancer consists of two phases: 1) 3-D MDCT analysis and 2) live bronchoscopy. Unfortunately, the yield rates for peripheral bronchoscopy have been reported to be as low as 14%, and bronchoscopy performance varies considerably between physicians. Recently, proposed image-guided systems have shown promise for assisting with peripheral bronchoscopy. Yet, MDCT-based route planning to target sites has relied on tedious error-prone techniques. In addition, route planning tends not to incorporate known anatomical, device, and procedural constraints that impact a feasible route. Finally, existing systems do not effectively integrate MDCT-derived route information into the live guidance process. We propose a system that incorporates an automatic optimal route-planning method, which integrates known route constraints. Furthermore, our system offers a natural translation of the MDCT-based route plan into the live guidance strategy via MDCT/video data fusion. An image-based study demonstrates the route-planning method's functionality. Next, we present a prospective lung-cancer patient study in which our system achieved a successful navigation rate of 91% to target sites. Furthermore, when compared to a competing commercial system, our system enabled bronchoscopy over two airways deeper into the airway-tree periphery with a sample time that was nearly 2 min shorter on average. Finally, our system's ability to almost perfectly predict the depth of a bronchoscope's navigable route in advance represents a substantial benefit of optimal route planning. PMID- 24235247 TI - Control-relevant erythropoiesis modeling in end-stage renal disease. AB - Anemia is prevalent in end-stage renal disease (ESRD). The discovery of recombinant human erythropoietin (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hb) measurements. In order to facilitate the design of an AMP using model-based feedback control theory, we present a physiologically relevant erythropoiesis model and demonstrate its applicability using clinical data. PMID- 24235248 TI - Lesion detection and characterization with context driven approximation in thoracic FDG PET-CT images of NSCLC studies. AB - We present a lesion detection and characterization method for (18)F fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) images of the thorax in the evaluation of patients with primary nonsmall cell lung cancer (NSCLC) with regional nodal disease. Lesion detection can be difficult due to low contrast between lesions and normal anatomical structures. Lesion characterization is also challenging due to similar spatial characteristics between the lung tumors and abnormal lymph nodes. To tackle these problems, we propose a context driven approximation (CDA) method. There are two main components of our method. First, a sparse representation technique with region-level contexts was designed for lesion detection. To discriminate low contrast data with sparse representation, we propose a reference consistency constraint and a spatial consistent constraint. Second, a multi-atlas technique with image-level contexts was designed to represent the spatial characteristics for lesion characterization. To accommodate inter-subject variation in a multi atlas model, we propose an appearance constraint and a similarity constraint. The CDA method is effective with a simple feature set, and does not require parametric modeling of feature space separation. The experiments on a clinical FDG PET-CT dataset show promising performance improvement over the state-of-the art. PMID- 24235250 TI - Neighborhood Supported Model Level Fuzzy Aggregation for Moving Object Segmentation. AB - We propose a new algorithm for moving object detection in the presence of challenging dynamic background conditions. We use a set of fuzzy aggregated multifeature similarity measures applied on multiple models corresponding to multimodal backgrounds. The algorithm is enriched with a neighborhood-supported model initialization strategy for faster convergence. A model level fuzzy aggregation measure driven background model maintenance ensures more robustness. Similarity functions are evaluated between the corresponding elements of the current feature vector and the model feature vectors. Concepts from Sugeno and Choquet integrals are incorporated in our algorithm to compute fuzzy similarities from the ordered similarity function values for each model. Model updating and the foreground/background classification decision is based on the set of fuzzy integrals. Our proposed algorithm is shown to outperform other multi-model background subtraction algorithms. The proposed approach completely avoids explicit offline training to initialize background model and can be initialized with moving objects also. The feature space uses a combination of intensity and statistical texture features for better object localization and robustness. Our qualitative and quantitative studies illustrate the mitigation of varieties of challenging situations by our approach. PMID- 24235249 TI - Adaptive image resizing based on continuous-domain stochastic modeling. AB - We introduce an adaptive continuous-domain modeling approach to texture and natural images. The continuous-domain image is assumed to be a smooth function, and we embed it in a parameterized Sobolev space. We point out a link between Sobolev spaces and stochastic auto-regressive models, and exploit it for optimally choosing Sobolev parameters from available pixel values. To this aim, we use exact continuous-to-discrete mapping of the auto-regressive model that is based on symmetric exponential splines. The mapping is computationally efficient, and we exploit it for maximizing an approximated Gaussian likelihood function.We account for non-Gaussian Levy-type processes by deriving a more robust estimator that is based on the sample auto-correlation sequence. Both estimators use multiple initialization values for overcoming the local minima structure of the fitting criteria. Experimental image resizing results indicate that the auto correlation criterion can cope better with non-Gaussian processes and model mismatch. Our work demonstrates the importance of the auto-correlation function in adaptive image interpolation and image modeling tasks, and we believe it is instrumental in other image processing tasks as well. PMID- 24235253 TI - Frame-Based Recovery of Corrupted Video Files Using Video Codec Specifications. AB - In digital forensics, recovery of a damaged or altered video file plays a crucial role in searching for evidences to resolve a criminal case. This paper presents a frame-based recovery technique of a corrupted video file using the specifications of a codec used to encode the video data. A video frame is the minimum meaningful unit of video data. Many existing approaches attempt to recover a video file using file structure rather than frame structure. In case a target video file is severely fragmented or even has a portion of video overwritten by other video content, however, video file recovery of existing approaches may fail. The proposed approach addresses how to extract video frames from a portion of video to be restored as well as how to connect extracted video frames together according to the codec specifications. Experiment results show that the proposed technique successfully restores fragmented video files regardless of the amount of fragmentations. For a corrupted video file containing overwritten segments, the proposed technique can recover most of the video content in non-overwritten segments of the video file. PMID- 24235255 TI - A dynamic evidential network for fall detection. AB - This study is part of the development of a remote home healthcare monitoring application designed to detect distress situations through several types of sensors. The multisensor fusion can provide more accurate and reliable information compared to information provided by each sensor separately. Furthermore, data from multiple heterogeneous sensors present in the remote home healthcare monitoring systems have different degrees of imperfection and trust. Among the multisensor fusion methods, Dempster-Shafer theory (DST) is currently considered the most appropriate for representing and processing the imperfect information. Based on a graphical representation of the DST called evidential networks, a structure of heterogeneous data fusion from multiple sensors for fall detection has been proposed. The evidential networks, implemented on our remote medical monitoring platform, are also proposed in this paper to maximize the performance of automatic fall detection and thus make the system more reliable. However, the presence of noise, the variability of recorded signals by the sensors, and the failing or unreliable sensors may thwart the evidential networks performance. In addition, the sensors signals nonstationary nature may degrade the experimental conditions. To compensate the nonstationary effect, the time evolution is considered by introducing the dynamic evidential network which was evaluated by the simulated fall scenarios corresponding to various use cases. PMID- 24235256 TI - Hardware and software realization of EDSD for acupuncture research and practice. AB - Traditional acupuncture as a diagnostic and therapeutic method has been known in China for more than 3000 years. Electrodermal screening tests (EDSTs) and electrodermal screening devices (EDSDs) that are based on the knowledge derived from traditional Chinese medicine appeared in the 1950s. This article deals with design, development and realization of such a device. The design considers the principles of two widely used EDSTs and modern trends in the field of electronics and data management. A computer program with simple user interface that provides graphic evaluation and intercomparison of measured data are presented. The designed system is suitable not only for acupuncture research but also for ordinary acupuncture diagnostics. PMID- 24235257 TI - SemInf: a burst-based semantic influence model for biomedical topic influence. AB - In this study, we model how biomedical topics influence one another, given they are organized in a topic hierarchy, medical subject headings, in which the edges capture a parent-child/subsumption relationship among topics. This information enables studying influence of topics from a semantic perspective, which might be very important in analyzing topic evolution and is missing from the current literature. We first define a burst-based action for topics, which models upward momentum in popularity (or "elevated occurrences" of the topics), and use it to define two types of influence: accumulation influence and propagation influence. We then propose a model of influence between topics, and develop an efficient algorithm (TIPS) to identify influential topics. Experiments show that our model is successful at identifying influential topics and the algorithm is very efficient. PMID- 24235258 TI - HCI?2 framework: a software framework for multimodal human-computer interaction systems. AB - This paper presents a novel software framework for the development and research in the area of multimodal human-computer interface (MHCI) systems. The proposed software framework, which is called the HCI?2 Framework, is built upon publish/subscribe (P/S) architecture. It implements a shared-memory-based data transport protocol for message delivery and a TCP-based system management protocol. The latter ensures that the integrity of system structure is maintained at runtime. With the inclusion of bridging modules, the HCI?2 Framework is interoperable with other software frameworks including Psyclone and ActiveMQ. In addition to the core communication middleware, we also present the integrated development environment (IDE) of the HCI?2 Framework. It provides a complete graphical environment to support every step in a typical MHCI system development process, including module development, debugging, packaging, and management, as well as the whole system management and testing. The quantitative evaluation indicates that our framework outperforms other similar tools in terms of average message latency and maximum data throughput under a typical single PC scenario. To demonstrate HCI?2 Framework's capabilities in integrating heterogeneous modules, we present several example modules working with a variety of hardware and software. We also present an example of a full system developed using the proposed HCI?2 Framework, which is called the CamGame system and represents a computer game based on hand-held marker(s) and low-cost camera(s). PMID- 24235259 TI - Takagi-Sugeno model based analysis of EWMA RtR control of batch processes with stochastic metrology delay and mixed products. AB - In many batch-based industrial manufacturing processes, feedback run-to-run control is used to improve production quality. However, measurements may be expensive and cannot always be performed online. Thus, the measurement delay always exists. The metrology delay will affect the stability and performance of the process. Moreover, since quality measurements are performed offline, delay is not fixed but is stochastic in nature. In this paper, a modeling approach Takagi Sugeno (T-S) model is presented to handle stochastic metrology delay in both single-product and mixed-product processes. Based on the Markov characteristics of the delay, the membership of the T-S model is derived. Performance indices such as the mean and the variance of the closed-loop output of the exponentially weighted moving average (EWMA) control algorithm can be derived. A steady-state error of the process output always exists, which leads the output deviating from the target. To remove the steady-state error, an algorithm called compensatory EWMA run-to-run (COM-EWMA-RtR) algorithm is proposed. The validity of the T-S model analysis and the efficiency of the proposed COM-EWMA-RtR algorithm are confirmed by simulation. PMID- 24235260 TI - Guest editorial: Introduction to the special issue on modern control for computer games. AB - A typical gaming scenario, as developed in the past 20 years, involves a player interacting with a game using a specialized input device, such as a joystic, a mouse, a keyboard, etc. Recent technological advances and new sensors (for example, low cost commodity depth cameras) have enabled the introduction of more elaborated approaches in which the player is now able to interact with the game using his body pose, facial expressions, actions, and even his physiological signals. A new era of games has already started, employing computer vision techniques, brain-computer interfaces systems, haptic and wearable devices. The future lies in games that will be intelligent enough not only to extract the player's commands provided by his speech and gestures but also his behavioral cues, as well as his/her emotional states, and adjust their game plot accordingly in order to ensure more realistic and satisfactory gameplay experience. This special issue on modern control for computer games discusses several interdisciplinary factors that influence a user's input to a game, something directly linked to the gaming experience. These include, but are not limited to, the following: behavioral affective gaming, user satisfaction and perception, motion capture and scene modeling, and complete software frameworks that address several challenges risen in such scenarios. PMID- 24235261 TI - Development and investigation of a long-range time-of-flight and color imaging system. AB - Time-of-flight (Tof) imaging based on the photonic mixer device (PMD) or similar ToF imaging solutions has been limited to short distances in the past, due to limited lighting devices and low sensitivity of ToF imaging chips. Long-range distance measurements are typically the domain of laser scanning systems. In this paper, PMD based medium- and long-range lighting devices working together with a 2-D/3-D camera are presented and several measurement results are discussed. The proposed imaging systems suffer from two systematic limitations in addition to problems due to wind and insufficient lighting: a low lateral resolution of the depth imaging chip and ambiguities in the distance measurements. In order to provide a robust and flexible system, we introduce algorithms to obtain unambiguous depth values (phase unwrapping) and to perform a joint motion compensation and super-resolution. Several experiments were conducted in order to evaluate the components of the multimodal imaging system. PMID- 24235262 TI - Addressing the EU sovereign ratings using an ordinal regression approach. AB - The current European debt crisis has drawn considerable attention to credit rating agencies' news about sovereign ratings. From a technical point of view, credit rating constitutes a typical ordinal regression problem because credit rating agencies generally present a scale of risk composed of several categories. This fact motivated the use of an ordinal regression approach to address the problem of sovereign credit rating in this paper. Therefore, the ranking of different classes will be taken into account for the design of the classifier. To do so, a novel model is introduced in order to replicate sovereign rating, based on the negative correlation learning framework. The methodology is fully described in this paper and applied to the classification of the 27 European countries' sovereign rating during the 2007-2010 period based on Standard and Poor's reports. The proposed technique seems to be competitive and robust enough to classify the sovereign ratings reported by this agency when compared with other existing well-known ordinal and nominal methods. PMID- 24235263 TI - Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. AB - Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV infected persons should be managed and monitored for all relevant age- and sex specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document. PMID- 24235264 TI - Statins and the risk of herpes zoster: a population-based cohort study. AB - BACKGROUND: Statins are widely used lipid-lowering drugs with immunomodulatory properties that may favor reactivation of latent varicella-zoster virus infection. However, whether statins increase the risk of herpes zoster is unknown. METHODS: We conducted a population-based retrospective cohort study of Ontario residents aged >= 66 years between 1 April 1997 and 31 March 2010 to examine the association between statin use and incidence of herpes zoster. We used propensity score matching to ensure similarity between users and nonusers of statins, and Cox proportional hazard models to assess differences in outcomes between study groups. To test the specificity of our findings, we examined the association between statin exposure and knee arthroplasty. RESULTS: During the 13 year study period, we matched 494 651 individuals treated with a statin to an equal number of untreated individuals. In the main analysis, the rate of herpes zoster was higher among users of statins relative to nonusers of these drugs (13.25 vs 11.71 per 1000 person-years, respectively; hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.10-1.17). The attributable fraction of exposed individuals was 11.6%. In a prespecified analysis, we found a similar risk of herpes zoster among statin users in the subgroup of patients with diabetes (HR, 1.18; 95% CI, 1.09-1.27). As expected, we found no association between statin use and knee arthroplasty (HR, 1.04; 95% CI, .99-1.09). CONCLUSIONS: Among older patients, treatment with statins is associated with a small but significantly increased risk of herpes zoster. PMID- 24235265 TI - Influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates. AB - BACKGROUND: Each year, the US Influenza Vaccine Effectiveness Network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza. METHODS: Patients with acute respiratory illnesses of <= 7 days' duration were enrolled at ambulatory care facilities in 5 communities. Specimens were collected and tested for influenza by real-time reverse-transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or immunization registries. Vaccine effectiveness was estimated in adjusted logistic regression models by comparing the vaccination coverage in those who tested positive for influenza with those who tested negative. RESULTS: The 2011-2012 season was mild and peaked late, with circulation of both type A viruses and both lineages of type B. Overall adjusted vaccine effectiveness was 47% (95% confidence interval [CI], 36-56) in preventing medically attended influenza; vaccine effectiveness was 65% (95% CI, 44-79) against type A (H1N1) pdm09 but only 39% (95% CI, 23-52) against type A (H3N2). Estimates of vaccine effectiveness against both type B lineages were similar (overall, 58%; 95% CI, 35 73). An apparent negative effect of prior year vaccination on current year effectiveness estimates was noted, particularly for A (H3N2) outcomes. CONCLUSIONS: Vaccine effectiveness in the 2011-2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus. This may be related to antigenic drift, but past history of vaccination might also play a role. PMID- 24235266 TI - Annual studies of influenza vaccine effectiveness: evaluating performance, informing policy, and generating new questions. PMID- 24235267 TI - Impact of nonischemic scar features on local ventricular electrograms and scar related ventricular tachycardia circuits in patients with nonischemic cardiomyopathy. AB - BACKGROUND: The association of local electrogram features with scar morphology and distribution in nonischemic cardiomyopathy has not been investigated. We aimed to quantify the association of scar on late gadolinium-enhanced cardiac magnetic resonance with local electrograms and ventricular tachycardia circuit sites in patients with nonischemic cardiomyopathy. METHODS AND RESULTS: Fifteen patients with nonischemic cardiomyopathy underwent late gadolinium-enhanced cardiac magnetic resonance before ventricular tachycardia ablation. The transmural extent and intramural types (endocardial, midwall, epicardial, patchy, transmural) of scar were measured in late gadolinium-enhanced cardiac magnetic resonance short-axis planes. Electroanatomic map points were registered to late gadolinium-enhanced cardiac magnetic resonance images. Myocardial wall thickness, scar transmurality, and intramural scar types were independently associated with electrogram amplitude, duration, and deflections in linear mixed-effects multivariable models, clustered by patient. Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P<0.0001 by ANOVA) and in regions with patchy scar (versus endocardial, midwall, epicardial scar; P<0.05 by ANOVA). Most ventricular tachycardia circuit sites were located in scar with >25% scar transmurality. CONCLUSIONS: Electrogram features are associated with scar morphology and distribution in patients with nonischemic cardiomyopathy. Previous knowledge of electrogram image associations may optimize procedural strategies including the decision to obtain epicardial access. PMID- 24235268 TI - Spatial profiles of electrical mismatch determine vulnerability to conduction failure across a host-donor cell interface. AB - BACKGROUND: Electrophysiological mismatch between host cardiomyocytes and donor cells can directly affect the electrical safety of cardiac cell therapies; however, the ability to study host-donor interactions at the microscopic scale in situ is severely limited. We systematically explored how action potential (AP) differences between cardiomyocytes and other excitable cells modulate vulnerability to conduction failure in vitro. METHODS AND RESULTS: AP propagation was optically mapped at 75 MUm resolution in micropatterned strands (n=152) in which host neonatal rat ventricular myocytes (AP duration=153.2+/-2.3 ms, conduction velocity=22.3+/-0.3 cm/s) seamlessly interfaced with genetically engineered excitable donor cells expressing inward rectifier potassium (Kir2.1) and cardiac sodium (Na(v)1.5) channels with either weak (conduction velocity=3.1+/-0.1 cm/s) or strong (conduction velocity=22.1+/-0.4 cm/s) electrical coupling. Selective prolongation of engineered donor cell AP duration (31.9-139.1 ms) by low-dose BaCl2 generated a wide range of host-donor repolarization time (RT) profiles with maximum gradients (?RT(max)) of 5.5 to 257 ms/mm. During programmed stimulation of donor cells, the vulnerable time window for conduction block across the host-donor interface most strongly correlated with ?RT(max). Compared with well-coupled donor cells, the interface composed of poorly coupled cells significantly shortened the RT profile width by 19.7% and increased ?RT(max) and vulnerable time window by 22.2% and 19%, respectively. Flattening the RT profile by perfusion of 50 MUmol/L BaCl2 eliminated coupling induced differences in vulnerability to block. CONCLUSIONS: Our results quantify how the degree of electrical mismatch across a cardiomyocyte-donor cell interface affects vulnerability to conduction block, with important implications for the design of safe cardiac cell and gene therapies. PMID- 24235269 TI - Fragmented QRS complex in adult patients with Ebstein anomaly and its association with arrhythmic risk and the severity of the anomaly. AB - BACKGROUND: Fragmented QRS complex (fQRS) on 12-lead ECG, a marker of myocardial scar, is a predictor of arrhythmic events in patients with ischemic and nonischemic cardiomyopathy. We investigated whether the presence of fQRS is associated with the severity of the anomaly and with increased arrhythmic events in adult patients with Ebstein anomaly (EA). METHODS AND RESULTS: In 51 consecutive adult patients with EA (median age, 37 years; 18 males), the severity index of EA calculated from echocardiographic data and clinical arrhythmic events were analyzed. The extent of fQRS in each patient was measured by counting the number of ECG leads showing fQRS. There were 35 (68.6%) patients with fQRS (fQRS group) and 16 (31.4%) patients without fQRS (non-fQRS group). fQRS was observed more frequently in the inferior (n=26) and precordial (n=25) leads versus the lateral leads (n=5). The patients in the fQRS group had a worse functional class, greater cardiothoracic ratios, more severe tricuspid regurgitation, larger atrialized right ventricular areas, higher EA severity scores, and more frequent arrhythmic events compared with those in the non-fQRS group. The atrialized right ventricular area showed a positive correlation with the fQRS extent (r=0.51; P<0.001). In multivariable Cox regression models, the presence of fQRS was independently associated with arrhythmic events (P=0.036). CONCLUSIONS: Fragmented QRS on 12-lead ECG was associated with larger atrialized right ventricular area and an increased risk of arrhythmic events in adult patients with EA. PMID- 24235271 TI - Peptide synthesis on glass substrate using acoustic droplet ejector. AB - This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip. PMID- 24235270 TI - Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation. AB - BACKGROUND: Cystic kidneys and vascular aneurysms are clinical manifestations seen in patients with polycystic kidney disease, a cilia-associated pathology (ciliopathy). Survivin overexpression is associated with cancer, but the clinical pathology associated with survivin downregulation or knockout has never been studied before. The present studies aim to examine whether and how cilia function (Pkd1 or Pkd2) and structure (Tg737) play a role in cystic kidney and aneurysm through survivin downregulation. METHODS AND RESULTS: Cysts and aneurysms from polycystic kidney disease patients, Pkd mouse, and zebrafish models are characterized by chromosome instability and low survivin expression. This triggers cytokinesis defects and formation of nuclear polyploidy or aneuploidy. In vivo conditional mouse and zebrafish models confirm that survivin gene deletion in the kidneys results in a cystic phenotype. As in hypertensive Pkd1, Pkd2, and Tg737 models, aneurysm formation can also be induced in vascular specific normotensive survivin mice. Survivin knockout also contributes to abnormal oriented cell division in both kidney and vasculature. Furthermore, survivin expression and ciliary localization are regulated by flow-induced cilia activation through protein kinase C, Akt and nuclear factor-kappaB. Circumventing ciliary function by re-expressing survivin can rescue polycystic kidney disease phenotypes. CONCLUSIONS: For the first time, our studies offer a unifying mechanism that explains both renal and vascular phenotypes in polycystic kidney disease. Although primary cilia dysfunction accounts for aneurysm formation and hypertension, hypertension itself does not cause aneurysm. Furthermore, aneurysm formation and cyst formation share a common cellular and molecular pathway involving cilia function or structure, survivin expression, cytokinesis, cell ploidy, symmetrical cell division, and tissue architecture orientation. PMID- 24235272 TI - Iterative reconstruction for x-ray computed tomography using prior-image induced nonlocal regularization. AB - Repeated X-ray computed tomography (CT) scans are often required in several specific applications such as perfusion imaging, image-guided biopsy needle, image-guided intervention, and radiotherapy with noticeable benefits. However, the associated cumulative radiation dose significantly increases as comparison with that used in the conventional CT scan, which has raised major concerns in patients. In this study, to realize radiation dose reduction by reducing the X ray tube current and exposure time (mAs) in repeated CT scans, we propose a prior image induced nonlocal (PINL) regularization for statistical iterative reconstruction via the penalized weighted least-squares (PWLS) criteria, which we refer to as "PWLS-PINL". Specifically, the PINL regularization utilizes the redundant information in the prior image and the weighted least-squares term considers a data-dependent variance estimation, aiming to improve current low dose image quality. Subsequently, a modified iterative successive overrelaxation algorithm is adopted to optimize the associative objective function. Experimental results on both phantom and patient data show that the present PWLS-PINL method can achieve promising gains over the other existing methods in terms of the noise reduction, low-contrast object detection, and edge detail preservation. PMID- 24235273 TI - High resolution (13)C MRI with hyperpolarized urea: in vivo T(2) mapping and (15)N labeling effects. AB - (13)C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [(13)C] urea and [(13) C,(15)N2] urea injected intravenously in rats. (15)N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [(13) C,(15) N2] urea giving T2 values of 6.3+/ 1.3 s in the cortex and medulla, and 11+/-2 s in the renal pelvis. The measured T2 in the aorta was 1.3+/-0.3 s. [(13)C] urea showed shortened T2 values in the kidney of 0.23+/-0.03 s compared to 0.28+/-0.03 s measured in the aorta. The enhanced T2 of [(13)C,(15)N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [(13)C,(15) N2] urea giving a greater than four-fold increase in signal-to-noise ratio over [(13)C] urea. PMID- 24235274 TI - Hierarchical manifold learning for regional image analysis. AB - We present a novel method of hierarchical manifold learning which aims to automatically discover regional properties of image datasets. While traditional manifold learning methods have become widely used for dimensionality reduction in medical imaging, they suffer from only being able to consider whole images as single data points. We extend conventional techniques by additionally examining local variations, in order to produce spatially-varying manifold embeddings that characterize a given dataset. This involves constructing manifolds in a hierarchy of image patches of increasing granularity, while ensuring consistency between hierarchy levels. We demonstrate the utility of our method in two very different settings: 1) to learn the regional correlations in motion within a sequence of time-resolved MR images of the thoracic cavity; 2) to find discriminative regions of 3-D brain MR images associated with neurodegenerative disease. PMID- 24235275 TI - Synthesis of walking sounds for alleviating gait disturbances in Parkinson's disease. AB - Managing gait disturbances in people with Parkinson's disease is a pressing challenge, as symptoms can contribute to injury and morbidity through an increased risk of falls. While drug-based interventions have limited efficacy in alleviating gait impairments, certain nonpharmacological methods, such as cueing, can also induce transient improvements to gait. The approach adopted here is to use computationally-generated sounds to help guide and improve walking actions. The first method described uses recordings of force data taken from the steps of a healthy adult which in turn were used to synthesize realistic gravel-footstep sounds that represented different spatio-temporal parameters of gait, such as step duration and step length. The second method described involves a novel method of sonifying, in real time, the swing phase of gait using real-time motion capture data to control a sound synthesis engine. Both approaches explore how simple but rich auditory representations of action based events can be used by people with Parkinson's to guide and improve the quality of their walking, reducing the risk of falls and injury. Studies with Parkinson's disease patients are reported which show positive results for both techniques in reducing step length variability. Potential future directions for how these sound approaches can be used to manage gait disturbances in Parkinson's are also discussed. PMID- 24235277 TI - Automatic identification and classification of freezing of gait episodes in Parkinson's disease patients. AB - Alternation of walking pattern decreases quality of life and may result in falls and injuries. Freezing of gait (FOG) in Parkinson's disease (PD) patients occurs occasionally and intermittently, appearing in a random, inexplicable manner. In order to detect typical disturbances during walking, we designed an expert system for automatic classification of various gait patterns. The proposed method is based on processing of data obtained from an inertial sensor mounted on shank. The algorithm separates normal from abnormal gait using Pearson's correlation and describes each stride by duration, shank displacement, and spectral components. A rule-based data processing classifies strides as normal, short (short(+)) or very short (short(-)) strides, FOG with tremor (FOG(+)) or FOG with complete motor block (FOG(-)). The algorithm also distinguishes between straight and turning strides. In 12 PD patients, FOG(+) and FOG(-) were identified correctly in 100% of strides, while normal strides were recognized in 95% of cases. Short(+) and short(-) strides were identified in about 84% and 78%. Turning strides were correctly identified in 88% of cases. The proposed method may be used as an expert system for detailed stride classification, providing warning for severe FOG episodes and near-fall situations. PMID- 24235276 TI - Simultaneous neural control of simple reaching and grasping with the modular prosthetic limb using intracranial EEG. AB - Intracranial electroencephalographic (iEEG) signals from two human subjects were used to achieve simultaneous neural control of reaching and grasping movements with the Johns Hopkins University Applied Physics Lab (JHU/APL) Modular Prosthetic Limb (MPL), a dexterous robotic prosthetic arm. We performed functional mapping of high gamma activity while the subject made reaching and grasping movements to identify task-selective electrodes. Independent, online control of reaching and grasping was then achieved using high gamma activity from a small subset of electrodes with a model trained on short blocks of reaching and grasping with no further adaptation. Classification accuracy did not decline (p < 0.05, one-way ANOVA) over three blocks of testing in either subject. Mean classification accuracy during independently executed overt reach and grasp movements for (Subject 1, Subject 2) were (0.85, 0.81) and (0.80, 0.96), respectively, and during simultaneous execution they were (0.83, 0.88) and (0.58, 0.88), respectively. Our models leveraged knowledge of the subject's individual functional neuroanatomy for reaching and grasping movements, allowing rapid acquisition of control in a time-sensitive clinical setting. We demonstrate the potential feasibility of verifying functionally meaningful iEEG-based control of the MPL prior to chronic implantation, during which additional capabilities of the MPL might be exploited with further training. PMID- 24235278 TI - Is accurate mapping of EMG signals on kinematics needed for precise online myoelectric control? AB - In this paper, we present a systematic analysis of the relationship between the accuracy of the mapping between EMG and hand kinematics and the control performance in goal-oriented tasks of three simultaneous and proportional myoelectric control algorithms: nonnegative matrix factorization (NMF), linear regression (LR), and artificial neural networks (ANN). The purpose was to investigate the impact of the precision of the kinematics estimation by a myoelectric controller for accurately complete goal-directed tasks. Nine naive subjects performed a series of goal-directed myoelectric control tasks using the three algorithms, and their online performance was characterized by 6 indexes. The results showed that, although the three algorithms' mapping accuracies were significantly different, their online performance was similar. Moreover, for LR and ANN, the offline performance was not correlated to any of the online performance indexes, and only a weak correlation was found with three of them for NMF . We conclude that for reliable simultaneous and proportional myoelectric control, it is not necessary to achieve high accuracy in the mapping between EMG and kinematics. Rather, good online myoelectric control is achieved by the continuous interaction and adaptation of the user with the myoelectric controller through feedback (visual in the current study). Control signals generated by EMG with rather poor association with kinematic variables can still be fully exploited by the user for precise control. This conclusion explains the possibility of accurate simultaneous and proportional control over multiple degrees of freedom when using unsupervised algorithms, such as NMF. PMID- 24235279 TI - Treatment planning and image guidance for radiofrequency ablation of large tumors. AB - This article addresses the two key challenges in computer-assisted percutaneous tumor ablation: planning multiple overlapping ablations for large tumors while avoiding critical structures, and executing the prescribed plan. Toward semiautomatic treatment planning for image-guided surgical interventions, we develop a systematic approach to the needle-based ablation placement task, ranging from preoperative planning algorithms to an intraoperative execution platform. The planning system incorporates clinical constraints on ablations and trajectories using a multiple objective optimization formulation, which consists of optimal path selection and ablation coverage optimization based on integer programming. The system implementation is presented and validated in both phantom and animal studies. The presented system can potentially be further extended for other ablation techniques such as cryotherapy. PMID- 24235280 TI - Designing a robust activity recognition framework for health and exergaming using wearable sensors. AB - Detecting human activity independent of intensity is essential in many applications, primarily in calculating metabolic equivalent rates and extracting human context awareness. Many classifiers that train on an activity at a subset of intensity levels fail to recognize the same activity at other intensity levels. This demonstrates weakness in the underlying classification method. Training a classifier for an activity at every intensity level is also not practical. In this paper, we tackle a novel intensity-independent activity recognition problem where the class labels exhibit large variability, the data are of high dimensionality, and clustering algorithms are necessary. We propose a new robust stochastic approximation framework for enhanced classification of such data. Experiments are reported using two clustering techniques, K-Means and Gaussian Mixture Models. The stochastic approximation algorithm consistently outperforms other well-known classification schemes which validate the use of our proposed clustered data representation. We verify the motivation of our framework in two applications that benefit from intensity-independent activity recognition. The first application shows how our framework can be used to enhance energy expenditure calculations. The second application is a novel exergaming environment aimed at using games to reward physical activity performed throughout the day, to encourage a healthy lifestyle. PMID- 24235281 TI - Optimal inverse functions created via population-based optimization. AB - Finding optimal inputs for a multiple-input, single-output system is taxing for a system operator. Population-based optimization is used to create sets of functions that produce a locally optimal input based on a desired output. An operator or higher level planner could use one of the functions in real time. For the optimization, each agent in the population uses the cost and output gradients to take steps lowering the cost while maintaining their current output. When an agent reaches an optimal input for its current output, additional agents are generated in the output gradient directions. The new agents then settle to the local optima for the new output values. The set of associated optimal points forms an inverse function, via spline interpolation, from a desired output to an optimal input. In this manner, multiple locally optimal functions can be created. These functions are naturally clustered in input and output spaces allowing for a continuous inverse function. The operator selects the best cluster over the anticipated range of desired outputs and adjusts the set point (desired output) while maintaining optimality. This reduces the demand from controlling multiple inputs, to controlling a single set point with no loss in performance. Results are demonstrated on a sample set of functions and on a robot control problem. PMID- 24235282 TI - Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle. AB - The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the gamma-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5 oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes. PMID- 24235284 TI - The demented patient who declines to be dialyzed and the unhappy armed police officer son: what should be done? AB - Dialysis personnel are responsible for ensuring that patients' rights and physical safety are protected in dialysis centers. Treatment of patients with cognitive impairment, including patients with dementia, presents special challenges. These patients may attempt to pull out their dialysis needles during treatment, potentially endangering themselves, dialysis center personnel, and other patients. Such patients may also compromise the care of other patients in the center by upsetting them and requiring a disproportionate amount of staff attention during treatment. Dialysis centers have learned to require families of such patients to provide a sitter to ensure that the patient remains safe during the dialysis treatment; however, some patients may exhibit unsafe behaviors despite a sitter, and not all families are willing to provide a sitter. In some instances, family members respond to the stress of a loved one who is unsafe on dialysis by being verbally or physically abusive to dialysis staff. This article presents a case in which the family member was a police officer who was not only verbally and physically intimidating to the staff but also insisted on bringing his police service weapon into the dialysis center. It describes the psychosocial, ethical, and legal responses to a family member who is disrupting what should be a calm environment in the dialysis center and recommends that dialysis centers proactively develop policies concerning safety for patients, family members, and other visitors that make no exceptions. The case also highlights the importance of adopting a no weapons policy and posting and enforcing a no weapons sign. PMID- 24235283 TI - Novel therapies for hemodialysis vascular access dysfunction: myth or reality? AB - Hemodialysis vascular access dysfunction is a major source of morbidity for patients with ESRD. Development of effective approaches to prevent and treat vascular access failure requires an understanding of the underlying mechanisms, suitable models for preclinical testing, systems for targeted delivery of interventions to maximize efficacy and minimize toxicity, and rigorous clinical trials that use appropriate outcome measures. This article reviews the substantial progress and ongoing challenges in developing novel treatments for arteriovenous vascular access failure and focuses on localized rather than systemic interventions. PMID- 24235285 TI - Pregnancy outcomes according to dialysis commencing before or after conception in women with ESRD. AB - BACKGROUND AND OBJECTIVES: Pregnancy in ESRD is rare and poses substantial risk for mother and baby. This study describes a large series of pregnancies in women undergoing long-term dialysis treatment and reviews maternal and fetal outcomes. Specifically, women who had conceived before and after starting long-term dialysis are compared. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: All pregnancies reported to the Australian and New Zealand Dialysis and Transplantation Registry from 2001 to 2011 (n=77), following the introduction of specific parenthood data collection, were analyzed. RESULTS: Between 2001 and 2011, there were 77 pregnancies among 73 women. Of these, 53 pregnancies were in women who conceived after long-term dialysis was established and 24 pregnancies occurred before dialysis began. The overall live birth rate (after exclusion of elective terminations) was 73%. In pregnancies reaching 20 weeks gestation, the live birth rate was 82%. Women who conceived before dialysis commenced had significantly higher live birth rates (91% versus 63%; P=0.03), but infants had similar birthweight and gestational age. This difference in live birth rate was primarily due to higher rates of early pregnancy loss before 20 weeks in women who conceived after dialysis was established. In pregnancies that reached 20 weeks or more, the live birth rate was higher in women with conception before dialysis commenced (91% versus 76%; P=0.28). Overall, the median gestational age was 33.8 weeks (interquartile range, 30.6-37.6 weeks) and median birthweight was 1750 g (interquartile range, 1130-2417 g). More than 40% of pregnancies reached >34 weeks' gestation; prematurity at <28 weeks was 11.4% and 28-day neonatal survival rate was 98%. CONCLUSIONS: Women with kidney disease who start long-term dialysis after conception have superior live birth rates compared with those already established on dialysis at the time of conception, although these pregnancies remain high risk. PMID- 24235286 TI - Renal relevant radiology: use of ultrasonography in patients with AKI. AB - As judged by the American College of Radiology Appropriateness Criteria, renal Doppler ultrasonography is the most appropriate imaging test in the evaluation of AKI and has the highest level of recommendation. Unfortunately, nephrologists are rarely specifically trained in ultrasonography technique and interpretation, and important clinical information obtained from renal ultrasonography may not be appreciated. In this review, the strengths and limitations of grayscale ultrasonography in the evaluation of patients with AKI will be discussed with attention to its use for (1) assessment of intrinsic causes of AKI, (2) distinguishing acute from chronic kidney diseases, and (3) detection of obstruction. The use of Doppler imaging and the resistive index in patients with AKI will be reviewed with attention to its use for (1) predicting the development of AKI, (2) predicting the prognosis of AKI, and (3) distinguishing prerenal azotemia from intrinsic AKI. Finally, pediatric considerations in the use of ultrasonography in AKI will be reviewed. PMID- 24235287 TI - Should an elderly patient with stage V CKD and dementia be started on dialysis? AB - The burden of cognitive impairment appears to increase with progressive renal disease, such that the prevalence of dementia among those starting dialysis, or those already established on dialysis, is high. The appropriateness of dialysis initiation in this population has been questioned, and current Renal Physician Association guidelines suggest forgoing dialysis in individuals who have dementia and lack awareness of self and environment. Patients are, however, also entitled to equal rights and respect, equal access to health care services, and an opportunity to engage in shared decision-making processes, particularly if there is concern over reversibility of disease. This article discusses, on the basis of principles of beneficence and nonmaleficence, the arguments in favor of and against dialysis use, and the process of determining an appropriate care plan. Factors discussed include the current societal trend toward a technological imperative, premature fatalism, survival benefits, and the implications of providing care to patients who are unable to express their tolerance for symptoms associated with the treatment or lack of treatment. PMID- 24235288 TI - The effects of frequent hemodialysis on left ventricular mass, volumes, and geometry. PMID- 24235290 TI - New adaptive clutter rejection based on spectral analysis for ultrasound color Doppler imaging: phantom and in vivo abdominal study. AB - Effective rejection of time-varying clutter originating from slowly moving vessels and surrounding tissues is important for depicting hemodynamics in ultrasound color Doppler imaging (CDI). In this paper, a new adaptive clutter rejection method based on spectral analysis (ACR-SA) is presented for suppressing nonstationary clutter. In ACR-SA, tissue and flow characteristics are analyzed by singular value decomposition and tissue acceleration of backscattered Doppler signals to determine an appropriate clutter filter from a set of clutter filters. To evaluate the ACR-SA method, 20 frames of complex baseband data were acquired by a commercial ultrasound system equipped with a research package (Accuvix V10, Samsung Medison, Seoul, Korea) using a 3.5-MHz convex array probe by introducing tissue movements to the flow phantom (Gammex 1425 A LE, Gammex, Middleton, WI, USA). In addition, 20 frames of in vivo abdominal data from five volunteers were captured. From the phantom experiment, the ACR-SA method provided 2.43 dB (p <; 0.001) and 1.09 dB ( ) improvements in flow signal-to-clutter ratio (SCR) compared to static (STA) and down-mixing (ACR-DM) methods. Similarly, it showed smaller values in fractional residual clutter area (FRCA) compared to the STA and ACR-DM methods (i.e., 2.3% versus 5.4% and 3.7%, respectively, ). The consistent improvements in SCR from the proposed ACR-SA method were obtained with the in vivo abdominal data (i.e., 4.97 dB and 3.39 dB over STA and ACR-DM, respectively). The ACR-SA method showed less than 1% FRCA values for all in vivo abdominal data. These results indicate that the proposed ACR-SA method can improve image quality in CDI by providing enhanced rejection of nonstationary clutter. PMID- 24235289 TI - Plasma and urinary amino acid metabolomic profiling in patients with different levels of kidney function. AB - BACKGROUND AND OBJECTIVES: Patients with CKD display altered plasma amino acid profiles. This study estimated the association between the estimated GFR and urinary and plasma amino acid profiles in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine and plasma samples were taken from 52 patients with different stages of CKD, and plasma samples only were taken from 25 patients on maintenance hemodialysis. Metabolic profiling was performed by liquid chromatography coupled with tandem mass spectrometry after phenylisothiocyanate derivatization. RESULTS: Most plasma amino acid concentrations were decreased in hemodialysis patients, whereas proline, citrulline, asparagine, asymmetric dimethylarginine, and hydroxykynurenine levels were increased (P<0.05). Both plasma levels and urinary excretion of citrulline were higher in the group of patients with advanced CKD (CKD stages 2 and 3 versus CKD stages 4 and 5; in plasma: 35.9+/-16.3 versus 61.8+/-23.6 umol/L, P<0.01; in urine: 1.0+/-1.2 versus 7.1+/-14.3 umol/mol creatinine, P<0.001). Plasma asymmetric dimethylarginine levels were higher in advanced CKD (CKD stages 2 and 3, 0.57+/-0.29; CKD stages 4 and 5, 1.02+/-0.48, P<0.001), whereas urinary excretion was lower (2.37+/-0.93 versus 1.51+/-1.43, P<0.001). Multivariate analyses adjusting on estimated GFR, serum albumin, proteinuria, and other covariates revealed associations between diabetes and plasma citrulline (P=0.02) and between serum sodium and plasma asymmetric dimethylarginine (P=0.03). Plasma tyrosine to phenylalanine and valine to glycine ratios were lower in advanced CKD stages (P<0.01). CONCLUSION: CKD patients have altered plasma and urinary amino acid profiles that are not corrected by dialysis. Depending on solutes, elevated plasma levels were associated with increased or decreased urinary excretion, depicting situations of uremic retention (asymmetric dimethylarginine) or systemic overproduction (citrulline). These results give some insight in the CKD-associated modifications of amino acid metabolism, which may help improve their handling. PMID- 24235291 TI - Combining motor imagery with selective sensation toward a hybrid-modality BCI. AB - A hybrid modality brain-computer interface (BCI) is proposed in this paper, which combines motor imagery with selective sensation to enhance the discrimination between left and right mental tasks, e.g., the classification between left/ right stimulation sensation and right/ left motor imagery. In this paradigm, wearable vibrotactile rings are used to stimulate both the skin on both wrists. Subjects are required to perform the mental tasks according to the randomly presented cues (i.e., left hand motor imagery, right hand motor imagery, left stimulation sensation or right stimulation sensation). Two-way ANOVA statistical analysis showed a significant group effect (F (2,20) = 7.17, p = 0.0045), and the Benferroni-corrected multiple comparison test (with alpha = 0.05) showed that the hybrid modality group is 11.13% higher on average than the motor imagery group, and 10.45% higher than the selective sensation group. The hybrid modality experiment exhibits potentially wider spread usage within ten subjects crossed 70% accuracy, followed by four subjects in motor imagery and five subjects in selective sensation. Six subjects showed statistically significant improvement ( Benferroni-corrected) in hybrid modality in comparison with both motor imagery and selective sensation. Furthermore, among subjects having difficulties in both motor imagery and selective sensation, the hybrid modality improves their performance to 90% accuracy. The proposed hybrid modality BCI has demonstrated clear benefits for those poorly performing BCI users. Not only does the requirement of motor and sensory anticipation in this hybrid modality provide basic function of BCI for communication and control, it also has the potential for enhancing the rehabilitation during motor recovery. PMID- 24235293 TI - Noncontact accurate measurement of cardiopulmonary activity using a compact quadrature Doppler radar sensor. AB - The designed sensor enables accurate reconstruction of chest-wall movement caused by cardiopulmonary activities, and the algorithm enables estimation of respiration, heartbeat rate, and some indicators of heart rate variability (HRV). In particular, quadrature receiver and arctangent demodulation with calibration are introduced for high linearity representation of chest displacement; 24-bit ADCs with oversampling are adopted for radar baseband acquisition to achieve a high signal resolution; continuous-wavelet filter and ensemble empirical mode decomposition (EEMD) based algorithm are applied for cardio/pulmonary signal recovery and separation so that accurate beat-to-beat interval can be acquired in time domain for HRV analysis. In addition, the wireless sensor is realized and integrated on a printed circuit board compactly. The developed sensor system is successfully tested on both simulated target and human subjects. In simulated target experiments, the baseband signal-to-noise ratio (SNR) is 73.27 dB, high enough for heartbeat detection. The demodulated signal has 0.35% mean squared error, indicating high demodulation linearity. In human subject experiments, the relative error of extracted beat-to-beat intervals ranges from 2.53% to 4.83% compared with electrocardiography (ECG) R-R peak intervals. The sensor provides an accurate analysis for heart rate with the accuracy of 100% for p = 2% and higher than 97% for p = 1%. PMID- 24235294 TI - Evaluating physiological dynamics via synchrosqueezing: prediction of ventilator weaning. AB - Oscillatory phenomena abound in many types of signals. Identifying the individual oscillatory components that constitute an observed biological signal leads to profound understanding about the biological system. The instantaneous frequency (IF), the amplitude modulation (AM), and their temporal variability are widely used to describe these oscillatory phenomena. In addition, the shape of the oscillatory pattern, repeated in time for an oscillatory component, is also an important characteristic that can be parametrized appropriately. These parameters can be viewed as phenomenological surrogates for the hidden dynamics of the biological system. To estimate jointly the IF, AM, and shape, this paper applies a novel and robust time-frequency analysis tool, referred to as the synchrosqueezing transform (SST). The usefulness of the model and SST are shown directly in predicting the clinical outcome of ventilator weaning. Compared with traditional respiration parameters, the breath-to-breath variability has been reported to be a better predictor of the outcome of the weaning procedure. So far, however, all these indices normally require at least 20 min of data acquisition to ensure predictive power. Moreover, the robustness of these indices to the inevitable noise is rarely discussed. We find that based on the proposed model, SST and only 3 min of respiration data, the ROC area under curve of the prediction accuracy is 0.76. The high predictive power that is achieved in the weaning problem, despite a shorter evaluation period, and the stability to noise suggest that other similar kinds of signal may likewise benefit from the proposed model and SST. PMID- 24235292 TI - Segmentation of PET images for computer-aided functional quantification of tuberculosis in small animal models. AB - Pulmonary infections often cause spatially diffuse and multi-focal radiotracer uptake in positron emission tomography (PET) images, which makes accurate quantification of the disease extent challenging. Image segmentation plays a vital role in quantifying uptake due to the distributed nature of immuno pathology and associated metabolic activities in pulmonary infection, specifically tuberculosis (TB). For this task, thresholding-based segmentation methods may be better suited over other methods; however, performance of the thresholding-based methods depend on the selection of thresholding parameters, which are often suboptimal. Several optimal thresholding techniques have been proposed in the literature, but there is currently no consensus on how to determine the optimal threshold for precise identification of spatially diffuse and multi-focal radiotracer uptake. In this study, we propose a method to select optimal thresholding levels by utilizing a novel intensity affinity metric within the affinity propagation clustering framework. We tested the proposed method against 70 longitudinal PET images of rabbits infected with TB. The overall dice similarity coefficient between the segmentation from the proposed method and two expert segmentations was found to be 91.25 +/-8.01% with a sensitivity of 88.80 +/-12.59% and a specificity of 96.01 +/-9.20%. High accuracy and heightened efficiency of our proposed method, as compared to other PET image segmentation methods, were reported with various quantification metrics. PMID- 24235295 TI - Efficient source separation algorithms for acoustic fall detection using a microsoft kinect. AB - Falls have become a common health problem among older adults. In previous study, we proposed an acoustic fall detection system (acoustic FADE) that employed a microphone array and beamforming to provide automatic fall detection. However, the previous acoustic FADE had difficulties in detecting the fall signal in environments where interference comes from the fall direction, the number of interferences exceeds FADE's ability to handle or a fall is occluded. To address these issues, in this paper, we propose two blind source separation (BSS) methods for extracting the fall signal out of the interferences to improve the fall classification task. We first propose the single-channel BSS by using nonnegative matrix factorization (NMF) to automatically decompose the mixture into a linear combination of several basis components. Based on the distinct patterns of the bases of falls, we identify them efficiently and then construct the interference free fall signal. Next, we extend the single-channel BSS to the multichannel case through a joint NMF over all channels followed by a delay-and-sum beamformer for additional ambient noise reduction. In our experiments, we used the Microsoft Kinect to collect the acoustic data in real-home environments. The results show that in environments with high interference and background noise levels, the fall detection performance is significantly improved using the proposed BSS approaches. PMID- 24235296 TI - Comparative evaluation of methodologies for T-wave alternans mapping in electrograms. AB - Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessible. T-wave alternans (TWA) is associated with increased vulnerability to ventricular tachycardia/fibrillation and it occurs before the onset of ventricular arrhythmias. Thus, accurate methodologies for time-varying alternans estimation/detection in EGM are needed. In this paper, we perform a simulation study based on epicardial EGM recorded in vivo in humans to compare the accuracy of four methodologies: the spectral method (SM), modified moving average method, laplacian likelihood ratio method (LLR), and a novel method based on time-frequency distributions. A variety of effects are considered, which include the presence of wide band noise, respiration, and impulse artifacts. We found that 1) EGM-TWA can be detected accurately when the standard deviation of wide-band noise is equal or smaller than ten times the magnitude of EGM-TWA. 2) Respiration can be critical for EGM-TWA analysis, even at typical respiratory rates. 3) Impulse noise strongly reduces the accuracy of all methods, except LLR. 4) If depolarization time is used as a fiducial point, the localization of the T wave is not critical for the accuracy of EGM-TWA detection. 5) According to this study, all methodologies provided accurate EGM-TWA detection/quantification in ideal conditions, while LLR was the most robust, providing better detection-rates in noisy conditions. Application on epicardial mapping of the in vivo human heart shows that EGM-TWA has heterogeneous spatio-temporal distribution. PMID- 24235297 TI - Prostate MRI segmentation using learned semantic knowledge and graph cuts. AB - We propose a fully automated method for prostate segmentation using random forests (RFs) and graph cuts. A volume of interest (VOI) is automatically selected using supervoxel segmentation, and its subsequent classification using image features and RF classifiers. The VOIs probability map is generated using image and context features, and a second set of RF classifiers. The negative log likelihood of the probability maps acts as the penalty cost in a second-order Markov random field cost function. Semantic information from the second set of RF classifiers is an important measure of each feature to the classification task, which contributes to formulating the smoothness cost. The cost function is optimized using graph cuts to get the final segmentation of the prostate. With average dice metric (DM) (on the training set) and DM (on the test set), our experimental results show that inclusion of the context and semantic information contributes to higher segmentation accuracy than other methods. PMID- 24235298 TI - Measurement of electrical coupling between cardiac ablation catheters and tissue. AB - Managing cardiac arrhythmias with catheter ablation requires positioning electrodes in contact with myocardial tissue. Objective measures to assess contact and effective coupling of ablation energy are sought. An electrical coupling index (ECI) was devised using complex impedance at 20 kHz to perform in the presence of RF ablation and deliver information about electrical interactions between the tip electrode and its adjacent environment. ECI was derived and compared with clinical judgment, pacing threshold, electrogram amplitude, and ablation lesion depth and transmurality in a porcine model. ECI was also compared with force and displacement using ex vivo bovine myocardial muscle. Mean noncontact ECI was 97.2 +/- 14.3 and increased to 145.2 +/- 33.6 (p <; 0.001) in clinician assessed (CLIN) moderate contact. ECI significantly improved CLIN's prediction of the variance in pacing threshold from 48.7% to 56.8% ( ). ECI was indicative of contact force under conditions of smooth myocardium. Transmural lesions were associated with higher pre-RF (109 +/- 17 versus 149 +/- 25, ) and during-RF (82 +/- 9 versus 101 +/- 17, ) ECI levels. ECI is a tip specific, robust, correlate with contact and ablation efficacy, and can potentially add to clinical interpretation of electrical coupling during electrophysiology procedures. PMID- 24235299 TI - Multi-Stencil Streamline Fast Marching: A General 3-D Framework to Determine Myocardial Thickness and Transmurality in Late Enhancement Images. AB - We propose a fully 3-D methodology for the computation of myocardial nonviable tissue transmurality in contrast enhanced magnetic resonance images. The outcome is a continuous map defined within the myocardium where not only current state-of the-art measures of transmurality can be calculated, but also information on the location of nonviable tissue is preserved. The computation is done by means of a partial differential equation framework we have called multi-stencil streamline fast marching. Using it, the myocardial and scarred tissue thickness is simultaneously computed. Experimental results show that the proposed 3-D method allows for the computation of transmurality in myocardial regions where current 2 D methods are not able to as conceived, and it also provides more robust and accurate results in situations where the assumptions on which current 2-D methods are based-i.e., there is a visible endocardial contour and its corresponding epicardial points lie on the same slice-, are not met. PMID- 24235300 TI - Quantifying the statistical impact of GRAPPA in fcMRI data with a real-valued isomorphism. AB - The interpolation of missing spatial frequencies through the generalized auto calibrating partially parallel acquisitions (GRAPPA) parallel magnetic resonance imaging (MRI) model implies a correlation is induced between the acquired and reconstructed frequency measurements. As the parallel image reconstruction algorithms in many medical MRI scanners are based on the GRAPPA model, this study aims to quantify the statistical implications that the GRAPPA model has in functional connectivity studies. The linear mathematical framework derived in the work of Rowe , 2007, is adapted to represent the complex-valued GRAPPA image reconstruction operation in terms of a real-valued isomorphism, and a statistical analysis is performed on the effects that the GRAPPA operation has on reconstructed voxel means and correlations. The interpolation of missing spatial frequencies with the GRAPPA model is shown to result in an artificial correlation induced between voxels in the reconstructed images, and these artificial correlations are shown to reside in the low temporal frequency spectrum commonly associated with functional connectivity. Through a real-valued isomorphism, such as the one outlined in this manuscript, the exact artificial correlations induced by the GRAPPA model are not simply estimated, as they would be with simulations, but are precisely quantified. If these correlations are unaccounted for, they can incur an increase in false positives in functional connectivity studies. PMID- 24235302 TI - Measures of effective video tracking. AB - To evaluate multitarget video tracking results, one needs to quantify the accuracy of the estimated target-size and the cardinality error as well as measure the frequency of occurrence of ID changes. In this paper, we survey existing multitarget tracking performance scores and, after discussing their limitations, we propose three parameter-independent measures for evaluating multitarget video tracking. The measures consider target-size variations, combine accuracy and cardinality errors, quantify long-term tracking accuracy at different accuracy levels, and evaluate ID changes relative to the duration of the track in which they occur. We conduct an extensive experimental validation of the proposed measures by comparing them with existing ones and by evaluating four state-of-the-art trackers on challenging real-world publicly-available data sets. The software implementing the proposed measures is made available online to facilitate their use by the research community. PMID- 24235301 TI - A mathematical framework for the registration and analysis of multi-fascicle models for population studies of the brain microstructure. AB - Diffusion tensor imaging (DTI) is unable to represent the diffusion signal arising from multiple crossing fascicles and freely diffusing water molecules. Generative models of the diffusion signal, such as multi-fascicle models, overcome this limitation by providing a parametric representation for the signal contribution of each population of water molecules. These models are of great interest in population studies to characterize and compare the brain microstructural properties. Central to population studies is the construction of an atlas and the registration of all subjects to it. However, the appropriate definition of registration and atlasing methods for multi-fascicle models have proven challenging. This paper proposes a mathematical framework to register and analyze multi-fascicle models. Specifically, we define novel operators to achieve interpolation, smoothing and averaging of multi-fascicle models. We also define a novel similarity metric to spatially align multi-fascicle models. Our framework enables simultaneous comparisons of different microstructural properties that are confounded in conventional DTI. The framework is validated on multi-fascicle models from 24 healthy subjects and 38 patients with tuberous sclerosis complex, 10 of whom have autism. We demonstrate the use of the multi-fascicle models registration and analysis framework in a population study of autism spectrum disorder. PMID- 24235303 TI - Oriented image foresting transform segmentation by seed competition. AB - Seed-based methods for region-based image segmentation are known to provide satisfactory results for several applications, being usually easy to extend to multidimensional images. However, while boundary-based methods like live wire can easily incorporate a preferred boundary orientation, regionbased methods are usually conceived for undirected graphs, and do not resolve well between boundaries with opposite orientations. This motivated researchers to investigate extensions for some region-based frameworks, seeking to better solve oriented transitions. In this same spirit, we discuss how to incorporate this orientation information in a region-based approach called "IFT segmentation by seed competition" by exploring digraphs. We give direct proof for the optimality of the proposed extensions in terms of energy functions associated with the cuts. To stress these theoretical results, we also present an experimental evaluation that shows the obtained gains in accuracy for some 2D and 3D data sets of medical images. PMID- 24235304 TI - Directionlets using in-phase lifting for image representation. AB - Directionlets allow a construction of perfect reconstruction and critically sampled multidirectional anisotropic basis, yet retaining the separable filtering of standard wavelet transform. However, due to the spatially varying filtering and downsampling direction, it is forced to apply spatial segmentation and process each segment independently. Because of this independent processing of the image segments, directionlets suffer from the following two major limitations when applied to, say, image coding. First, failure to exploit the correlation across block boundaries degrades the coding performance and also induces blocking artifacts, thus making it mandatory to use deblocking filter at low bit rates. Second, spatial scalability, i.e., minimum segment size or the number of levels of the transform, is limited due to independent processing of segments. We show that, with simple modifications in the block boundaries, we can overcome these limitations by, what we call, in-phase lifting implementation of directionlets. In the context of directionlets using in-phase lifting, we identify different possible groups of downsampling matrices that would allow the construction of a multilevel transform without forcing independent processing of segments both with and without any modifications in the segment boundary. Experimental results in image coding show objective and subjective improvements when compared with the directionlets applied independently on each image segment. As an application, using both the in-phase lifting implementation of directionlets and the adaptive directional lifting, we have constructed an adaptive directional wavelet transform, which has shown improved image coding performance over these adaptive directional wavelet transforms. PMID- 24235305 TI - Tension in active shapes. AB - The concept of tension is introduced in the framework of active contours with prior shape information, and it is used to improve image segmentation. In particular, two properties of this new quantity are shown: 1) high values of the tension correspond to undesired equilibrium points of the cost function under minimization and 2) tension decreases if a curve is split into two or more parts. Based on these ideas, a tree is generated whose nodes are different local minima of the cost function. Deeper nodes in the tree are expected to correspond to lower values of the cost function. In this way, the search for the global optimum is reduced to visiting and pruning a binary tree. The proposed method has been applied to the problem of fish segmentation from low quality underwater images. Qualitative and quantitative comparison with existing algorithms based on the Euler-Lagrange diffusion equations shows the superiority of the proposed approach in avoiding undesired local minima. PMID- 24235306 TI - Multiple Description Coding With Randomly and Uniformly Offset Quantizers. AB - In this paper, two multiple description coding schemes are developed, based on prediction-induced randomly offset quantizers and unequal-deadzone-induced near uniformly offset quantizers, respectively. In both schemes, each description encodes one source subset with a small quantization stepsize, and other subsets are predictively coded with a large quantization stepsize. In the first method, due to predictive coding, the quantization bins that a coefficient belongs to in different descriptions are randomly overlapped. The optimal reconstruction is obtained by finding the intersection of all received bins. In the second method, joint dequantization is also used, but near-uniform offsets are created among different low-rate quantizers by quantizing the predictions and by employing unequal deadzones. By generalizing the recently developed random quantization theory, the closed-form expression of the expected distortion is obtained for the first method, and a lower bound is obtained for the second method. The schemes are then applied to lapped transform-based multiple description image coding. The closed-form expressions enable the optimization of the lapped transform. An iterative algorithm is also developed to facilitate the optimization. Theoretical analyzes and image coding results show that both schemes achieve better performance than other methods in this category. PMID- 24235307 TI - Variational exemplar-based image colorization. AB - In this paper, we address the problem of recovering a color image from a grayscale one. The input color data comes from a source image considered as a reference image. Reconstructing the missing color of a grayscale pixel is here viewed as the problem of automatically selecting the best color among a set of color candidates while simultaneously ensuring the local spatial coherency of the reconstructed color information. To solve this problem, we propose a variational approach where a specific energy is designed to model the color selection and the spatial constraint problems simultaneously. The contributions of this paper are twofold. First, we introduce a variational formulation modeling the color selection problem under spatial constraints and propose a minimization scheme, which computes a local minima of the defined nonconvex energy. Second, we combine different patch-based features and distances in order to construct a consistent set of possible color candidates. This set is used as input data and our energy minimization automatically selectsthe best color to transfer for each pixel of the grayscale image. Finally, the experiments illustrate the potentiality of our simple methodology and show that our results are very competitive with respect to the state-of-the-art methods. PMID- 24235308 TI - Partitioning kinetic energy during freewheeling wheelchair maneuvers. AB - This paper describes a systematic method to partition the kinetic energy (KE) of a free-wheeling wheelchair. An ultralightweight rigid frame wheelchair was instrumented with two axle-mounted encoders and data acquisition equipment to accurately measure the velocity of the drive wheels. A mathematical model was created combining physical specifications and geometry of the wheelchair and its components. Two able-bodied subjects propelled the wheelchair over four courses that involved straight and turning maneuvers at differing speeds. The KE of the wheelchair was divided into three components: translational, rotational, and turning energy. This technique was sensitive to the changing contributions of the three energy components across maneuvers. Translational energy represented the major component of total KE in all maneuvers except a zero radius turn in which turning energy was dominant. Both translational and rotational energies are directly related to wheelchair speed. Partitioning KE offers a useful means of investigating the dynamics of a moving wheelchair. The described technique permits analysis of KE imparted to the wheelchair during maneuvers involving changes in speed and direction, which are most representative of mobility in everyday life. This technique can be used to study the effort required to maneuver different types and configurations of wheelchairs. PMID- 24235309 TI - An SVM-wrapped multiobjective evolutionary feature selection approach for identifying cancer-microRNA markers. AB - MicroRNAs (miRNAs), have been shown to play important roles in gene regulation and various biological processes. Recent studies have revealed that abnormal expression of some specific miRNAs often results in the development of cancer. Microarray datasets containing the expression profiles of several miRNAs are being used for identification of miRNAs which are differentially expressed in normal and malignant tissue samples. In this article, a multiobjective feature selection approach is proposed for this purpose. The proposed method uses Genetic Algorithm for multiobjective optimization and support vector machine (SVM) classifier as a wrapper for evaluating the chromosomes that encode feature subsets. The performance has been demonstrated on real-life miRNA datasets for and the identified miRNA markers are reported. Moreover biological significance tests have been carried out for the obtained markers. PMID- 24235310 TI - Idealizing ion channel recordings by a jump segmentation multiresolution filter. AB - Based on a combination of jump segmentation and statistical multiresolution analysis for dependent data, a new approach called J-SMURF to idealize ion channel recordings has been developed. It is model-free in the sense that no a priori assumptions about the channel's characteristics have to be made; it thus complements existing methods which assume a model for the channel's dynamics, like hidden Markov models. The method accounts for the effect of an analog filter being applied before the data analysis, which results in colored noise, by adapting existing muliresolution statistics to this situation. J-SMURF's ability to denoise the signal without missing events even when the signal-to-noise ratio is low is demonstrated on simulations as well as on ion current traces obtained from gramicidin A channels reconstituted into solvent-free planar membranes. When analyzing a newly synthesized acylated system of a fatty acid modified gramicidin channel, we are able to give statistical evidence for unknown gating characteristics such as subgating. PMID- 24235311 TI - Noncontact proximity vital sign sensor based on PLL for sensitivity enhancement. AB - In this paper, a noncontact proximity vital sign sensor, using a phase locked loop (PLL) incorporated with voltage controlled oscillator (VCO) built-in planar type circular resonator, is proposed to enhance sensitivity in severe environments. The planar type circular resonator acts as a series feedback element of the VCO as well as a near-field receiving antenna. The frequency deviation of the VCO related to the body proximity effect ranges from 0.07 MHz/mm to 1.8 MHz/mm (6.8 mV/mm to 205 mV/mm in sensitivity) up to a distance of 50 mm, while the amount of VCO drift is about 21 MHz in the condition of 60 ( degrees )C temperature range and discrete component tolerance of +/- 5%. Total frequency variation occurs in the capture range of the PLL which is 60 MHz. Thus, its loop control voltage converts the amount of frequency deviation into a difference of direct current (DC) voltage, which is utilized to extract vital signs regardless of the ambient temperature. The experimental results reveal that the proposed sensor placed 50 mm away from a subject can reliably detect respiration and heartbeat signals without the ambiguity of harmonic signals caused by respiration signal at an operating frequency of 2.4 GHz. PMID- 24235312 TI - Multiview comodeling to improve subtyping and genetic association of complex diseases. AB - Genetic association analysis of complex diseases has been limited by heterogeneity in their clinical manifestations and genetic etiology. Research has made it possible to differentiate homogeneous subtypes of the disease phenotype. Currently, the most sophisticated subtyping methods perform unsupervised cluster analysis using only clinical features of a disorder, resulting in subtypes for which genetic association may be limited. In this study, we seek to derive a novel multiview data analytic method that integrates two views of the data: the clinical features and the genetic markers of the same set of patients. Our method is based on multiobjective programming that is capable of clinically categorizing a disease phenotype so as to discover genetically different subtypes.We optimize two objectives jointly: 1) in cluster analysis, the derived clusters should differ significantly in clinical features; 2) these clusters can be well separated using genetic markers by constructed classifiers. Extensive computational experiments with two substance-use disorders using two populations show that the proposed algorithm is superior to existing subtyping methods. PMID- 24235313 TI - Limited correlation between conventional pathologist and automatic computer assisted quantification of hepatic steatosis due to difference between event based and surface-based analysis. AB - Computer-assisted automatic quantification (CAQ) was developed as an alternative method for the diagnosis of hepatic steatosis in order to compensate for observer dependent bias. Here, we aim to demonstrate that CAQ can provide an accurate and precise result in analysis of fatty content, but that it is inappropriate to validate CAQ by comparison with conventional pathologist estimation (PE). Male rats were fed with a methionine-choline-deficient plus high-fat diet for three days, one week, or two weeks to induce mild, moderate, or severe steatosis. Samples were collected from all liver lobes. Severity of hepatic steatosis was assessed by an experienced pathologist who estimated the percentage of hepatocytes containing lipid droplets. Fatty content was quantified by PE, CAQ, and biochemical analysis (BA). CAQ, PE, and BA can correctly reflect severe fatty change. However, in the case of mild and moderate steatosis, PE could not reflect the true fatty content ( r between PE and BA was <0). The result of CAQ correlated well with that of BA among the various degrees of severity of hepatic steatosis. In conclusion, due to a difference between event-based and surface based analysis, it is inappropriate to validate the CAQ of hepatic steatosis by comparison with PE. PMID- 24235314 TI - sEMG-based joint force control for an upper-limb power-assist exoskeleton robot. AB - This paper investigates two surface electromyogram (sEMG)-based control strategies developed for a power-assist exoskeleton arm. Different from most of the existing position control approaches, this paper develops force control methods to make the exoskeleton robot behave like humans in order to provide better assistance. The exoskeleton robot is directly attached to a user's body and activated by the sEMG signals of the user's muscles, which reflect the user's motion intention. In the first proposed control method, the forces of agonist and antagonist muscles pair are estimated, and their difference is used to produce the torque of the corresponding joints. In the second method, linear discriminant analysis-based classifiers are introduced as the indicator of the motion type of the joints. Then, the classifier's outputs together with the estimated force of corresponding active muscle determine the torque control signals. Different from the conventional approaches, one classifier is assigned to each joint, which decreases the training time and largely simplifies the recognition process. Finally, the extensive experiments are conducted to illustrate the effectiveness of the proposed approaches. PMID- 24235315 TI - Local mesh patterns versus local binary patterns: biomedical image indexing and retrieval. AB - In this paper, a new image indexing and retrieval algorithm using local mesh patterns are proposed for biomedical image retrieval application. The standard local binary pattern encodes the relationship between the referenced pixel and its surrounding neighbors, whereas the proposed method encodes the relationship among the surrounding neighbors for a given referenced pixel in an image. The possible relationships among the surrounding neighbors are depending on the number of neighbors, P. In addition, the effectiveness of our algorithm is confirmed by combining it with the Gabor transform. To prove the effectiveness of our algorithm, three experiments have been carried out on three different biomedical image databases. Out of which two are meant for computer tomography (CT) and one for magnetic resonance (MR) image retrieval. It is further mentioned that the database considered for three experiments are OASIS-MRI database, NEMA CT database, and VIA/I-ELCAP database which includes region of interest CT images. The results after being investigated show a significant improvement in terms of their evaluation measures as compared to LBP, LBP with Gabor transform, and other spatial and transform domain methods. PMID- 24235316 TI - Manikin-integrated digital measuring system for assessment of infant cardiopulmonary resuscitation techniques. AB - The process of cardiopulmonary resuscitation (CPR) involves various components that must be followed to deliver high quality of CPR. While the components commonly apply to CPR for all ages from infant to adult, there are several different suggestions for infant CPR such as two-thumb CPR and two-finger CPR. However, the comprehensive evaluation based on all these components has been difficult in the absence of proper evaluation tool. Here, we developed a new manikin-integrated, digital measuring system that objectively estimates overall performance of infant CPR by evaluating individual CPR components one by one including different hand placements. The system collects and analyzes data to present estimations in digital scores according to a new evaluation index constructed based on the previously verified one. The feasibility of the system was validated through simulations with beginners and experts in first aid, resulting in statistically significant differences between the two groups with the indication of specific weaknesses for each group which may provide a basis for creating customized CPR training strategy in compliance with the personal level. We believe that the system would become a valuable assessment tool not only for infant CPR but also for the CPR technique, in general, by reflecting every component in the evaluation. PMID- 24235317 TI - Tensor-based methods for handling missing data in quality-of-life questionnaires. AB - A common problem with self-report quality-of-life questionnaires is missing data. Despite enormous care and effort to prevent it, some level of missing data is common and unavoidable. Missing data can have a detrimental impact on the data analysis. In this paper, a novel approach to imputing missing data in quality-of life questionnaires is proposed, based on matrix and tensor decompositions. In order to illustrate and assess those methods, two datasets are considered: The first dataset contains the responses of 100 patients to a systemic lupus erythematosus-specific quality-of-life questionnaire; the other contains the responses of 43 patients to a rhino-conjunctivitis quality-of-life questionnaire. The two datasets contain almost no missing data, and for testing purposes, data entries are removed at random to have missing completely at random data. Several proportions of missing values are considered, and for each, the imputation error is assessed through k-fold cross validation. We also evaluate different imputation methods for missing at random and missing not at randomdata. The numerical results demonstrate that the proposed tensor factorization-based methods outperform standard methods in terms of root mean square error with at least 4% improvement, while the bias and variance are similar. PMID- 24235318 TI - Adaptive shape prior constrained level sets for bladder MR image segmentation. AB - Three-dimensional bladder wall segmentation for thickness measuring can be very useful for bladder magnetic resonance (MR) image analysis, since thickening of the bladder wall can indicate abnormality. However, it is a challenging task due to the artifacts inside bladder lumen, weak boundaries in the apex and base areas, and complicated outside intensity distributions. To deal with these difficulties, in this paper, an adaptive shape prior constrained directional level set model is proposed to segment the inner and outer boundaries of the bladder wall. In addition, a coupled directional level set model is presented to refine the segmentation by exploiting the prior knowledge of region information and minimum thickness. With our proposed method, the influence of the artifacts in the bladder lumen and the complicated outside tissues surrounding the bladder can be appreciably reduced. Furthermore, the leakage on the weak boundaries can be avoided. Compared with other related methods, better results were obtained on 11 patients' 3-D bladder MR images by using the proposed method. PMID- 24235319 TI - Accelerometry-based berg balance scale score estimation. AB - The objective of the study was to investigate the validity of 3-D-accelerometry based Berg balance scale (BBS) score estimation. In particular, acceleration patterns of BBS tasks and gait were the targets of analysis. Accelerations of the lower back were measured during execution of the BBS test and corridor walking for 54 subjects, consisting of neurological patients, older adults, and healthy young persons. The BBS score was estimated from one to three BBS tasks and from gait-related data, separately, through assessment of the similarity of acceleration patterns between subjects. The work also validated both approaches' ability to classify subjects into high- and low-fall-risk groups. The gait-based method yielded the best BBS score estimates and the most accurate BBS-task-based estimates were produced with the stand to sit, reaching, and picking object tasks. The proposed gait-based method can identify subjects with high or low risk of falling with an accuracy of 77.8% and 96.6%, respectively, and the BBS-task based method with corresponding accuracy of 89.5% and 62.1%. PMID- 24235320 TI - In-stent neoatherosclerosis 10 years after bare metal stent implantation: ruptured vulnerable plaque by optical coherence tomography. PMID- 24235321 TI - Emergent cardiac surgery during transcatheter aortic valve implantation (TAVI): insights from the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry. AB - AIMS: Transcatheter aortic valve implantation (TAVI) carries the risk of intraprocedural complications that may ultimately require emergent cardiac surgery (ECS). However, few data exist on the incidence, reasons and outcomes of patients needing ECS during TAVI. We analysed data from 2,307 TAVI patients, prospectively enrolled in the multicentre Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry. METHODS AND RESULTS: Twenty-seven (1.2%) of 2,307 patients required ECS. The rates of ECS were similar for patients undergoing transapical TAVI compared with transfemoral TAVI (1.1% vs. 1.2%). The leading causes for ECS were embolisation/migration of the TAVI valve prosthesis (9/27, 33%) and procedure-related aortic injury (n=7, 26%). Thirty-day mortality of ECS was high (51.9%) and showed cause-specific differences, with 100% mortality in patients with aortic rupture or cardiac tamponade, 0% death in those with acute aortic regurgitation and intermediate risk of death or intermediate mortality in those with aortic injury or valve embolisation/migration. CONCLUSIONS: Rates of ECS during TAVI were low (1.2%). Although ECS was performed without time delay, emergent surgery was associated with a 30-day mortality of 52%. Complications with dramatic acute consequences (annular rupture, aortic injury) had higher mortality than those with less acute deterioration (aortic regurgitation). Prevention of complications requiring ECS during TAVI appears to be of critical importance, focusing on less traumatic, more flexible delivery catheter systems and retrievable valves to reduce the risk of aortic injury and valve embolisation, the two most common causes of ECS. PMID- 24235322 TI - [Illustrations of an innovate laboratory medicine]. PMID- 24235323 TI - [Infections transmitted from the mother to the fetus: diagnostic issues and management of pregnancy]. AB - Some infections are considered as feared risks during pregnancy. These infections may lead to severe damage of the fetus or the newborn depending on the infectious agent and the term of pregnancy where the infection occurred. Antenatal screening (in France it concerns toxoplasmosis, rubella, syphilis and hepatitis B) play an important role in prevention and management of vertically transmissible infections. However, biological diagnosis is also essential when maternal/neo natal clinical symptoms or abnormal ultrasound findings are observed. In this article we chose to focus on rubella, varicella, syphilis, toxoplasmosis, hepatitis B and cytomegalovirus and parvovirus infections. PMID- 24235324 TI - [Hepatitis B: clinical application of HBsAg quantification]. AB - Since its discovery by Blumberg in 1965, hepatitis B virus antigen (HBsAg) is used as the fingerprint of hepatitis B infection. HBsAg level reflects the transcriptional activity of the cccDNA. It is an important marker that might not only indicate active hepatitis B infection, but may also predict clinical and treatment outcomes. Assays for HBsAg quantification are fully automated with a high output capacity. HBsAg titer is higher in HBe antigen (HBeAg) positive chronic hepatitis B than in HBeAg negative patients and is negatively correlated with liver fibrosis in HBeAg positive patients. In HBeAg negative chronic hepatitis B, an HBsAg level < 1,000 IU/mL and an HBV DNA titer < 2,000 IU/mL allow the accurate identification of inactive carriers. On pegylated-interferon (PEG-IFN) treatment, HBsAg quantification allows identifying, as early as week 12 PEG-IFN therapy, patients that will not benefit from therapy and thus stop or switch treatment "week 12 stopping rule". Genotype A and D: stop at week 12 if no HBsAg decrease; Genotype B and C: stop at week 12 if titer > 20,000 UI/mL. With regards to nucleos[t]ides analogues therapy the role of HBsAg quantification remains to be clarified. Several studies indicate that baseline and on-treatment HBsAg levels might allow identifying patients that can end up with treatment with no subsequent risk of reactivation. In clinical practice, HBsAg quantification is a simple and reproducible worthwhile tool that can be used in association with HBV DNA to classify patients during HBV infection and to monitor therapy. PMID- 24235325 TI - [HPV testing in prevention of cervical cancer: practices and current trends]. AB - Robust evidence supports new strategies for prevention of cervical cancer based on the detection of persistent Human papillomavirus (HPV) infection, the causative agent of the disease. New HPV infection is usually benign and transient, while persistent infection with one of -high risk HPV explains almost all of these cancers. In fact, the detection of one of the 12 oncogenic HPV increase the sensitivity of the screening and predicts, sooner than cytology, the risk of precancerous lesions, the high grade of cervical intraepithelial neoplasia (HG CIN). Negative HPV detection gives instantaneously a reassurance close to 100% of absence of disease at risk (while cytology detection is less than 60%) and almost guarantees protection of the absence of HG CIN over a prolonged period, allowing lengthening safely the screening interval to 5 years. Pooled HPV-based screening tests decrease the specificity of the screening and increases the number of colposcopy. New strategies can significantly improve the specificity of HPV screening without a significant impact on the sensitivity, including exclusion of women less than 30 years, the use of HPV DNA genotyping tests with recognition of the most HPV at risk, the 16 and 18 types. HPV alone can be used as a screening tool in women of 30 years + with a cytology triage or immunocytochemical staining of cyto slides for p16 of HPV positive. Co-testing (cytology+ HPV test) was adopted in the USA as a standard screening option. PMID- 24235326 TI - [Interpretation of mild elevation of high-sensitivity cardiac troponins]. AB - Measurements of cardiac troponins (cTn) are yet considered the gold standard method in patients with chest pain. Very recently, high-sensitivity (hs)cTn emerged and allow to measure very low concentrations of cTn. The aim of these assays was the better detection of patients with acute myocardial infarction (AMI). The threshold value should be the 99th percentile of the method, which corresponds to the concentration obtained from 99% of a reference population. These assays improve the detection of patients with elevated cTn concentrations. All patients with increased hs-cTn concentration above the 99th percentile should be considered at high risk of future clinical event when compared to patients with lower concentration. However, these elevated concentrations are not necessarily related to AMI due to coronary artery plaque rupture and superimposed thrombus. In order to understand adequately cTn measurement, the physician should base his interpretation on the context, the cTn concentration, variations during serial sampling, and the possible existence of a coexistent disease characterized by increased cTn concentrations. PMID- 24235327 TI - [Interest of NT-proBNP in chronic heart failure follow-up]. AB - Reducing readmissions after hospitalisation for acute heart failure is the new challenge of these diseases, approaching 30% within 60 to 90 days of discharge. Congestion related to high ventricular filling pressures, reflected by the high levels of natriuretic peptides, is the main reason for heart failure readmission. Natriuretic peptide levels are a patent prognostic marker of cardiovascular event in chronic heart failure. Treshold values of BNP and NT-proBNP being respectively 125 and 1000 pg/mL. Optimizing treatment of heart failure by monitoring natriuretic peptides, including management of diuretic doses, remains matter of controversies. PMID- 24235328 TI - [The usefulness of platelet function evaluation in clinical practice]. AB - Platelets play a pivotal role in the regulation of both thrombosis and haemostasis. Functional testing of platelet response has been exclusively used in the diagnosis and management of bleeding disorders. Recent advances of light transmission aggregometry and development of more useful devices have demonstrated the clinical utility to enlarge platelet function testing in patients with cardiovascular disease. The ex vivo measurement of residual platelet response seems, with some assays, predictive of adverse clinical events. Still a debate, it represents an emerging area of interest for both the clinician and the basic scientist. Heparin-induced thrombocytopenia diagnosis is also difficult and a functional assay is now available for an easier and rapid method to rule out such a life-threatening situation. This review article will describe the available methods of measuring platelet response and will discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice. PMID- 24235329 TI - [Near-patient testing devices to monitor vitamin K antagonists]. AB - Monitoring of the anticoagulant effect with the International normalized ratio (INR) is essential for patients receiving vitamin K antagonists (VKAs). The majority of point of care (POC) devices for INR monitoring has shown a good precision and accuracy with results similar to those obtained in a laboratory. In many countries, INR POC devices are widely used at home by the patients for self testing. Their use in the hospital by the clinical staff (doctor or nurses) for bedside measurement is also growing. The INR POC testing is performed using fully automated devices. Capillary blood samples are easy to obtain. In the emergency room, POC INR devices are commonly used. This improves the quality of care for patient with suspicion of VKAs overdosage. INR measurement using bedside monitors is also of great interest in care units for specific populations of patients like paediatrics or geriatrics. Moreover, bedside INR monitoring may be useful in anticoagulant clinics or when the care unit is far from a laboratory. Although the bedside INR monitors are easy to use, their implementation requires adequate training and intermittent re-evaluation of any person performing the tests to ensure reliability of results. Such equipment must comply with EN ISO 22870 standard for POC testing accreditation, under the supervision of a biologist. In order to achieve these targets, connect the instrument to the laboratory's data management system is essential. PMID- 24235330 TI - [S100B protein serum level as a biomarker of minor head injury]. AB - S100B is a small protein selectively synthesized by cerebral astroglial cells. S100B participates physiologically in the regulation of intracellular free calcium levels, and exerts a neurotrophic activity on cerebral cells. The interest of S100B protein in clinical biology results from its physiological presence in biological fluids (cerebrospinal fluid, blood, urine) and from significant increased levels when an acute brain injury occurred, from vascular (intracranial hemorrhage, ischemic stroke) or traumatic (traumatic brain injury) origins. Thus, elevated plasma concentrations of S100B were significantly increased in patients with a minor, moderate and of course severe traumatic brain injury. By contrast, serum S100B levels remained unchanged in patients with negative craniocerebral tomography results, confirming the diagnostic value of this biomarker. A prognostic value of the biomarker in the context of minor head injury is also reported. PMID- 24235331 TI - [Biology and markers of preeclampsia]. AB - Preeclampsia is a syndrome specific of pregnancy and placenta diagnosed after 20 WG on the association of an hypertension and a proteinuria. It is responsible for significant maternal-fetal morbidity and mortality which justify the development of markers for screening, diagnosis and prognosis. These markers are actors or witnesses to the various stages and mechanisms of the disease : the initial defect of trophoblast invasion and remodeling of uterine arteries (proteases [PAPP-A, ADAM-12, uPA, MMPs], their inhibitors, and angiogenic factors [PlGF, sflt-1, s-eng]) which induces hydrostatic abnormalities (uterine doppler) and placental hypoperfusion with dysoxia (HIF-1alpha) and oxidative stress (free radicals, peroxynitrites, oxidized LDL). This results in impaired placental functions including endocrine and metabolic functions (hCG, leptin) with increase in placental apoptosis and necrosis with the release of exosomes and toxic placental fragments (STBM) and their content (RNA, DNA and proteins). This fragments amplify the gestational inflammation (IL6, TNFalpha ; activation of leukocytes and macrophages [elastase, neopterin] and complement) and lead to a deterioration of the maternal endothelium (vasoconstriction [ET2, TxA2]; platelet adhesion [sVCAM -1alpha), aggregation and activation; impaired vascular permeability) generating edema, hypertension, atherosclerosis and glomerular nephropathy (proteinuria, hyperuricemia). Other markers such as PP13 and PTX3 seem of interest even if their functions are poorly understood. Preeclampsia develops on a predisposed maternal environment (genetic, epigenetic infectious, and endocrine factors) characterized by a maternal inadequacy to pregnancy. PMID- 24235332 TI - [Response predictive biomarkers to targeted therapies in oncology]. AB - Cancer kills 147,500 people each year in France. The development of personalized therapies and more recently theranostics, completely changed the biological approach to this disease. Thus, the already well-known but sparsely specific serum markers are being replaced by new tumor markers, predictive of resistance or response to targeted therapies. The study of these biomarkers is performed by different technical approaches, which are essentially based molecular biology assays. These determinations are assessed in France within the 28 molecular tumor genetics platforms approved by French National Cancer Institute (INCa). The most commonly used assays for this type of molecular diagnostics, such as real-time PCR, the sequencing, immunohistochemistry, FISH or CISH, are relatively difficult because most of them are based on the use of formalin fixed paraffin embedded tumor tissues. This paper provides a synthesis of validated theranostic biomarkers and the most used diagnostic methods, but also draw a point on the best incoming biomarkers candidates and assays in close development using liquid biopsies. PMID- 24235333 TI - Residents'corner July 2013. DeRmpath & Clinic: Basocellular carcinomas with metastatic potential. PMID- 24235771 TI - A hot and dry future: warming effects on boreal tree drought tolerance. PMID- 24235772 TI - Tuberculin test can be read after 24 hours in adolescent children. AB - OBJECTIVE: To assess readability of 24-h tuberculin response in adolescent school children. DESIGN: Prospective observational study in school. SUBJECTS: 601 healthy adolescent children. INTERVENTIONS: Tuberculin (1TU PPD RT23 Tween80) was administered and indurations at 24 and 72 h were compared. MAIN OUTCOME MEASURE: Tuberculin reaction at 24 h. RESULTS: One hundred twelve children (18.6%) had a positive tuberculin reaction. Prevalence of tuberculin positivity was least (14.2%) in the 10-year age-group and maximum in the 13-year age-group (21.2%). When individual values of tuberculin reaction at 24 and 72 h were compared, a significant difference was noted irrespective of the tuberculin status (t = 8.46, p = 0.001). However, when tuberculin reaction was considered as positive or negative, this difference was not significant (t = 1.89, p > 0.05). CONCLUSIONS: Tuberculin status in adolescents can be read as positive or negative at 24 h, irrespective of their bacillus Calmette-Guerin scar status. PMID- 24235770 TI - Utility of B-13 progenitor-derived hepatocytes in hepatotoxicity and genotoxicity studies. AB - AR42J-B-13 (B-13) cells form hepatocyte-like (B-13/H) cells in response to glucocorticoid treatment. To establish its utility in toxicity and genotoxicity screening, cytochrome P450 (CYP) induction, susceptibility to toxins, and transporter gene expression were examined. Conversion to B-13/H cells resulted in expression of male-specific CYP2C11 and sensitivity to methapyrilene. B-13/H cells constitutively expressed CYP1A, induced expression in response to an aryl hydrocarbon receptor agonist, and activated benzo[alpha]pyrene to a DNA-damaging species. Functional CYP1A2 was not expressed due to deletions in the Cyp1a2 gene. A B-13 cell line stably expressing the human CYP1A2 was therefore engineered (B 13(-TR/h1A2)) and the derived B-13/H cells expressed metabolically functional CYP1A2. Treatment with the cooked food mutagen 2-amino-1-methyl-6 phenylimidazo(4,5-b)pyridine resulted in a dose-dependent increase in DNA damage. B-13/H cells expressed constitutive androstane receptor (CAR) and induced CYP2B1 mRNA levels in response to classical CAR activators. However, translation to functional CYP2B1 protein was low and increased minimally by CAR activator treatment. B-13/H cells expressed high levels of pregnane X-receptor (PXR) and induced CYP3A1 in response to classical PXR activators. CYP3A genes were inducible, functional, and activated aflatoxin B1 to a DNA-damaging species. All 23 major hepatic transporters were induced when B-13 cells were converted to B 13/H cells, although in many cases, levels remained below those present in adult rat liver. However, bile salt export pump, Abcb1b, multidrug resistance associated protein, and breast cancer resistance protein transporters were functional in B-13/H cells. These data demonstrate that the B-13 cell generates hepatocyte-like cells with functional drug metabolism and transporter activities, which can alone--or in a humanized form--be used to screen for hepatotoxic and genotoxic endpoints in vitro. PMID- 24235773 TI - Influence of successive badminton matches on muscle strength, power, and body fluid balance in elite players. AB - The aim was to analyze the influence of competitive round on muscle strength, body-fluid balance, and renal function in elite badminton players during a real competition. Body mass, jump height during a countermovement jump, handgrip force, and urine samples were obtained from 13 elite badminton players (6 men and 7 women) before and after the 2nd-round and quarterfinal matches of the national Spanish badminton championship. Sweat rate was determined by using prematch-to postmatch body-mass change and by weighing individually labeled fluid bottles. Sweat rates were 1.04 +/- 0.62 and 0.98 +/- 0.43 L/h, while rehydration rate was 0.69 +/- 0.26 and 0.91 +/- 0.52 L/h for the 2nd round and quarterfinals, respectively. Thus, dehydration was 0.47% +/- 1.03% after the 2nd round and 0.23% +/- 0.43% after the quarterfinals. There were no differences in prematch-to postmatch jump height, but jump height was reduced from 37.51 +/- 8.83 cm after the 2nd-round game to 34.82 +/- 7.37 cm after the quarterfinals (P < .05). No significant differences were found in handgrip force when comparing prepost matches or rounds, although there were significant differences between dominant and nondominant hands (P < .05). The succession of rounds caused the appearance of proteinuria, hematuria, glycosuria, and higher nitrite and ketone concentrations in urine. Rehydration patterns during a real badminton competition were effective to prevent dehydration. A badminton match did not affect jump height or handgrip force, but jump height was progressively reduced by the competitive round. Badminton players' renal responses reflected diminished renal flux due to the high-intensity nature of this racket sport. PMID- 24235774 TI - Coaches' and players' perceptions of training dose: not a perfect match. AB - PURPOSE: The aim of the current study was to investigate and compare coaches' and players' perceptions of training dose for a full competitive season. METHODS: Session rating of perceived exertion (RPE), duration, and training load (session RPE * duration) of 33 professional soccer players (height 178.2 +/- 6.6 cm, weight 70.5 +/- 6.4 kg, percentage body fat 12.2 +/- 1.6) from an under-19 and under-17 (U17) squad were compared with the planned periodization of their professional coaches. Before training, coaches filled in the session rating of intended exertion (RIE) and duration (min) for each player. Players rated session RPE and training duration after each training session. RESULTS: Players perceived their intensity and training load (2446 sessions in total) as significantly harder than what was intended by their coaches (P < .0001). The correlations between coaches' and players' intensity (r = .24), duration (r = .49), and load (r = .41) were weak (P < .0001). Furthermore, for coach-intended easy and intermediate training days, players reported higher intensity and training load (P < .0001). For hard days as intended by the coach, players reported lower intensity, duration, and training load (P < .0001). Finally, first-year players from the U17 squad perceived training sessions as harder than second-year players (P < .0001). CONCLUSION: The results indicate that young elite soccer players perceive training as harder than what was intended by the coach. These differences could lead to maladaptation to training. Monitoring of the planned and perceived training load of coaches and players may optimize performance and prevent players from overtraining. PMID- 24235775 TI - Time to exhaustion at continuous and intermittent maximal lactate steady state during running exercise. AB - The purpose of this study was to determine and compare the time to exhaustion (TE) and the physiological responses at continuous and intermittent (ratio 5:1) maximal lactate steady state (MLSS) in well-trained runners. Ten athletes (32.7 +/- 6.9 y, VO2max 61.7 +/- 3.9 mL . kg-1 . min-1) performed an incremental treadmill test, three to five 30-min constant-speed tests to determine the MLSS continuous and intermittent (5 min of running, interspaced by 1 min of passive rest), and 2 randomized TE tests at such intensities. Two-way ANOVA with repeated measures was used to compare the changes in physiological variables during the TE tests and between continuous and intermittent exercise. The intermittent MLSS velocity (MLSSint = 15.26 +/- 0.97 km/h) was higher than in the continuous model (MLSScon = 14.53 +/- 0.93 km/h), while the TE at MLSScon was longer than MLSSint (68 +/- 11 min and 58 +/- 15 min, P < .05). Regarding the cardiorespiratory responses, VO2 and respiratory-exchange ratio remained stable during both TE tests while heart rate, ventilation, and rating of perceived exertion presented a significant increase in the last portion of the tests. The results showed a higher tolerance to exercising during MLSScon than during MLSSint in trained runners. Thus, the training volume of an extensive interval session (ratio 5:1) designed at MLSS intensity should take into consideration this higher speed at MLSS and also the lower TE than with continuous exercise. PMID- 24235776 TI - Variability in power output during cycling in international Olympic-distance triathlon. AB - PURPOSE: The patterns of power output in the ~1-h cycle section of Olympic distance triathlon races are not well documented. Here the authors establish a typical cycling-race profile derived from several International Triathlon Union elite-level drafting-legal triathlon races. METHODS: The authors collated 12 different race power profiles from elite male triathletes (N = 5, age 25 +/- 5 y, body mass 65.5 +/- 5.6 kg; mean +/- SD) during 7 international races. Power output was recorded using SRM cranks and analyzed with proprietary software. RESULTS: The mean power output was 252 +/- 33 W, or 3.9 +/- 0.5 W/kg in relative terms, with a coefficient of variation of 71% +/- 13%. Normalized power (power output an athlete could sustain if intensity were maintained constant without any variability) for the entire cycle section was 291 +/- 29 W, or 40 +/- 13 W higher than the actual mean power output. There were 34 +/- 14 peaks of power output above 600 W and ~18% time spent at >100% of maximal aerobic power. CONCLUSION: Cycling during Olympic-distance triathlon, characterized by frequent and large power variations including repeat supramaximal efforts, equates to a higher workload than cycling at constant power. PMID- 24235777 TI - Paying the Piper: The High Cost of Funerals in South Africa. AB - We analyze funeral arrangements following the deaths of 3,751 people who died between January 2003 and December 2005 in the Africa Centre Demographic Surveillance Area. We find that, on average, households spend the equivalent of a year's income for an adult's funeral, measured at median per capita African (Black) income. Approximately one-quarter of all individuals had some form of insurance, which helped surviving household members defray some fraction of funeral expenses. However, an equal fraction of households borrowed money to pay for the funeral. We develop a model, consistent with ethnographic work in this area, in which households respond to social pressure to bury their dead in a style consistent with the observed social status of the household and that of the deceased. Households that cannot afford a funeral commensurate with social expectations must borrow money to pay for the funeral. The model leads to empirical tests, and we find results consistent with our model of household decision-making. PMID- 24235778 TI - Modulation of electrochemical hydrogen evolution rate by araliphatic thiol monolayers on gold. AB - Electroreductive desorption of a highly ordered self-assembled monolayer (SAM) formed by the araliphatic thiol (4-(4-(4-pyridyl)phenyl)phenyl)methanethiol leads to a concurrent rapid hydrogen evolution reaction (HER). The desorption process and resulting interfacial structure were investigated by voltammetric techniques, in situ spectroscopic ellipsometry, and in situ vibrational sum-frequency generation (SFG) spectroscopy. Voltammetric experiments on SAM-modified electrodes exhibit extraordinarily high peak currents, which di er between Au(111) and polycrystalline Au substrates. Association of reductive desorption with HER is shown to be the origin of the observed excess cathodic charges. The studied SAM preserves its two-dimensional order near Au surface throughout a fast voltammetric scan even when the vertex potential is set several hundred millivolt beyond the desorption potential. A model is developed for the explanation of the observed rapid HER involving ordering and pre-orientation of water present in the nanometer-sized reaction volume between desorbed SAM and the Au electrode, by the structurally extremely stable monolayer, leading to the observed catalysis of the HER. PMID- 24235779 TI - The Effects of Low Income Housing Tax Credit Developments on Neighborhoods. AB - This paper evaluates the impacts of new housing developments funded with the Low Income Housing Tax Credit (LIHTC), the largest federal project based housing program in the U.S., on the neighborhoods in which they are built. A discontinuity in the formula determining the magnitude of tax credits as a function of neighborhood characteristics generates pseudo-random assignment in the number of low income housing units built in similar sets of census tracts. Tracts where projects are awarded 30 percent higher tax credits receive approximately six more low income housing units on a base of seven units per tract. These additional new low income developments cause homeowner turnover to rise, raise property values in declining areas and reduce incomes in gentrifying areas in neighborhoods near the 30th percentile of the income distribution. LIHTC units significantly crowd out nearby new rental construction in gentrifying areas but do not displace new construction in stable or declining areas. PMID- 24235780 TI - Paid Sick Leave and Job Stability. AB - A compelling, but unsubstantiated, argument for paid sick leave legislation is that workers with leave are better able to address own and family member health needs without risking a voluntary or involuntary job separation. This study tests that claim using the Medical Expenditure Panel Survey and regression models controlling for a large set of worker and job characteristics, as well as with propensity score techniques. Results suggest that paid sick leave decreases the probability of job separation by at least 2.5 percentage points, or 25%. The association is strongest for workers without paid vacation leave and for mothers. PMID- 24235781 TI - Third-order effects in resonant sum-frequency-generation signals at electrified metal/liquid interfaces. AB - Vibrational sum-frequency-generation (SFG) spectroscopy experiments at electrified interfaces involve incident laser radiation at frequencies in the IR and near-IR/visible regions as well as a static electric field on the surface. Here we show that mixing the three fields present on the surface can result in third-order effects in resonant SFG signals. This was achieved for closed packed self-assembled monolayers (SAMs) with molecular groups of high optical nonlinearity and surface potentials similar to those typically applied in cyclic voltammograms. Broadband SFG spectroscopy was applied to study a hydrophobic well ordered araliphatic SAM on a Au(111) surface using a thin-layer analysis cell for spectro-electrochemical investigations in a 100 mM NaOH electrolyte solution. Resonant contributions were experimentally separated from non-resonant contributions of the Au substrate and theoretically analyzed using a fitting function including third-order terms. The resulting ratio of third-order to second-order susceptibilities was estimated to be [Formula: see text](10-10) m/V. PMID- 24235782 TI - Cultural Socialization in Families with Adopted Korean Adolescents: A Mixed Method, Multi-Informant Study. AB - Transracial, transnational families understand and transmit cultural socialization messages in ways that differ from same-race families. This study explored the ways in which transracial, transnational adoptive families discuss race and ethnicity and how these family discussions compared to self-reports from adoptive parents and adolescents regarding the level of parental engagement in cultural socialization. Of the thirty families with at least one adolescent-aged child (60% female, average age 17.8 years) who was adopted from South Korea, nine families acknowledged racial and ethnic differences, six families rejected racial and ethnic differences, and fifteen families held a discrepancy of views. Parents also reported significantly greater engagement in cultural socialization than adolescents' reports of parental engagement. However, only adolescent self reports of parental engagement in cultural socialization matched the qualitative coding of family conversations. PMID- 24235783 TI - FROM EXCLUSION TO INTERNATIONAL MIGRATION: THE CASE OF LATINO YOUTHS. AB - In this article, I refer to structural tendencies reflected in the responses of excluded Latinos youths, who range from street children to radical youths (gangs or not) and finally to migrants. The latter, face unusual challenges as a result of being undocumented, forcing them to pursue mobility within a formal system that blocks their way. I review these tendencies through a "positive" lens, focusing mainly on Latino youth who are using different strategies to fight social exclusion. I aim to raise the paradoxical temporality, which indicates that as we learn and analyze more, we tend to move further away from the possibility of transforming pressing problems in society. I raise the question of how to intervene using more knowledge in the alarming situation of one of the most excluded social groups, Latino Youth and also of how to alert and visualize ways of integrating those youth who migrate and become undocumented. PMID- 24235784 TI - Entrapment of a volatile lipophilic aroma compound (d-limonene) in spray dried water-washed oil bodies naturally derived from sunflower seeds (Helianthus annus). AB - Oil bodies are natural emulsions that can be extracted from oil seeds and have previously been shown to be stable after spray drying. The aim of the study was to evaluate for the first time if spray dried water-washed oil bodies are an effective carrier for volatile lipophilic actives (the flavour compound d limonene was used as an example aroma compound). Water-washed oil bodies were blended with maltodextrin and d-limonene and spray dried using a Buchi B-191 laboratory spray dryer. Lipid and d-limonene retention was 89-93% and 24-27%. Samples were compared to processed emulsions containing sunflower oil and d limonene and stabilised by either lecithin or Capsul. Lecithin and Capsul processed emulsions had a lipid and d-limonene retention of 82-89%, 7.7-9.1% and 48-50%, 55-59% respectively indicating that water-washed oil bodies could retain the most lipids and Capsul could retain the most d-limonene. This indicates that whilst additional emulsifiers may be required for future applications of water washed oil bodies as carriers of lipophilic actives, oil bodies are excellent agents for lipid encapsulation. PMID- 24235785 TI - The last editorial. PMID- 24235786 TI - Percutaneous management of renal caliceal diverticular stones: Ten-year experience of a tertiary care center with different techniques to deal with diverticula after stone extraction. AB - INTRODUCTION: Caliceal diverticulae are a frequent surgical problem. We present our experience with caliceal diverticular stones (CDS) managed with percutaneous nephrolithotomy (PCNL) and describe the two different techniques to deal with diverticula after stone retrieval. MATERIALS AND METHODS: We retrospectively analyzed 10-year data of 44 consecutive patients who underwent PCNL for CDS. During PCNL, if the guide wire could be negoted through the neck of the diverticula, we dilated and stented it. If we couldnot find the neck, we fulgurated the diverticular walls. Follow-up included intravenous urogram at 3 months and annual plain films thereafter. We analyzed the outcome, complications, and recurrence rate. RESULTS: Total stone clearance was obtained in 40 (90.90%) patients. We dilated and stented the diverticula in 35 (79.5%) patients and fulgurated the walls in nine (20.5%) patients. Complications occurred in three patients. The postoperative intravenous urogram showed obliteration of diverticula in seven patients and the improved drainage in 37 patients. At the average follow-up of 2 years, 41 (93.18%) patients were asymptomatic and two (4.5%) patients showed the recurrence of stone. CONCLUSIONS: PCNL can clear calculi from caliceal diverticula in most cases with minimal morbidity. After stone retrieval, the diverticula may be drained into the pyelocaliceal system, if the neck is negotiable and fulgurated if the neck cannot be dilated. PMID- 24235787 TI - Hemagglutination and biofilm formation as virulence markers of uropathogenic Escherichia coli in acute urinary tract infections and urolithiasis. AB - INTRODUCTION: Urinary tract infections (UTI) are a major public health concern in developing countries. Most UTIs are caused by E. coli, accounting for up to 90% of community-acquired UTIs (CAUTI). Recurrent UTI is considered as a major risk factor for urolithiasis. Virulence factors like adhesins and biofilm have been extensively studied by authors on UPEC isolated from recurrent UTI. The studies on isolates from infection stones in kidney are scanty. In a prospective study, we aimed to determine the expression of Haemagglutinins, (Type 1 and P fimbriae), Biofilm production and resistance pattern to common antibiotics of Uropathogenic E.coli (UPEC) isolates from Community acquired Acute Urinary Tract Infection(CAUTI) and Urolithiasis. MATERIALS AND METHODS: A total of 43 UPEC isolates, 23 mid-stream urine (MSU) samples from patients with CAUTI attending Out Patient Departments and 20 from renal calculi of urolithiasis patients at the time of Percutaneous nephrolithostomy (PCNL) were included in the study and the expression of Haemagglutinins,(Type 1 and P fimbriae), Biofilm production and resistance pattern to common antibiotics was assessed. RESULTS: A total of 43 UPEC isolates 23 from CAUTI and 20 from renal calculi were tested for production of biofilm and hemagglutinins. In CAUTI, biofilm producers were 56.52% and hemagglutinins were detected in all isolates 100%. In urolithiasis, biofilm producers were 100% but hemagglutinins were detected only in 70% of isolates. All isolates were resistant to multiple antibiotics used. CAUTI isolates were susceptible to 3(rd) generation cephalosporins, whereas urolithiasis isolates were resistant to 3(rd) generation cephalosporins and 25% were Extended Spectrum Beta Lactamases ESBL producers. CONCLUSIONS: HA mediated by type 1 fimbriae plays an important role in CAUTI (P < 0.001 highly significant), whereas, in chronic conditions like urolithiasis, biofilm plays an important role in persistence of infection and the role of hemagglutinins is less. PMID- 24235788 TI - Warty carcinoma of the penis: A clinicopathological study from South India. AB - AIMS: There are few studies on the pathology of warty carcinoma (WC) of the penis and these have been from South America. Penile cancers are not uncommon in India. We reviewed the frequency of subtypes of penile squamous carcinoma (SC) and the pathological features and outcome of WC when compared to squamous carcinoma-not otherwise specified (SC-NOS). We also compared the clinicopathological features of WC in our series with those published earlier. MATERIALS AND METHODS: We studied 103 cases of penile cancers over 6 years. Cases were classified into different subtypes according to established histologic criteria. Clinicopathologic features were studied in detail and compared among the different subtypes, especially between WC and SC-NOS. The patients were followed up and disease free survival in months was noted. RESULTS: SC-NOS constituted 75.7% of all penile cancer cases in our series. The frequency of other subtypes was WC: 9.7%, verrucous: 3.9%, basaloid type and papillary type: 0.97% each, and mixed types 8.7%. The average tumor size and depth of invasion did not differ significantly between the two subtypes. Frequency of lymphovascular emboli and percentage of lymph node metastasis in WC (30 and 10%) were lesser than in SC-NOS (49.37 and 26.58%), respectively. There were no recurrences after partial penectomy in the WC subtype. In the SC-NOS type, three cases had recurrence after partial/total penectomy. CONCLUSION: Warty carcinoma constitutes nearly 10% of all penile squamous cell cancers. These patients seem to have a less aggressive behavior than SC-NOS. PMID- 24235789 TI - Penile growth in response to hormone treatment in children with micropenis. AB - INTRODUCTION: Micropenis is defined as a stretched penile length 2.5 standard deviations less than the mean for age without the presence of any other penile anomalies, such as hypospadias. The term refers to a specific disorder that has a known set of causative factors and defined treatment modalities. The purpose of this study was to determine the effect of hormonal therapy on the gonadal response and penile growth in children who presented with micropenis. MATERIALS AND METHODS: Children (<18 years) who met the criteria for micropenis were included in this study. Children more than 11 years old were treated using a standard protocol of 1,500 to 2,000 IU human chorionic gonadotrophin administrated intramuscularly, once per week, for 6 weeks. Children less than 11 years old were treated with parenteral testosterone enanthate 25 mg once a month for 3 months. Response was evaluated in terms of change in testosterone levels and size of penis. RESULTS: Serum testosterone levels at baseline and after 8 weeks of hormonal treatment were <20 and 449.4 ng/mL, respectively (P < 0.0001) in all children more than 11 years old. Stretched penile length after hormonal treatment increased from 15.54 to 37.18 mm in children less than 11 years old and from 26.42 to 64.28 mm in children more than 11 years old (P < 0.001). CONCLUSIONS: Management of isolated micropenis revolves around testosterone (direct administration or encouraging the patient's body to make its own), and results with respect to increase in penile length are promising. PMID- 24235790 TI - Urological reconstruction in the modern era. PMID- 24235791 TI - Management of secondary pelviureteric junction obstruction. AB - Pelviureteric junction obstruction (PUJO) of the kidney can lead to a number of different clinical manifestations, which often require surgical intervention. Although the success of pyeloplasty and endopyelotomy are good, there are still a number of patients who fail primary treatment and develop secondary PUJO. These treatment failures can be a challenging cohort to manage. This article aims to provide a comprehensive overview on the surgical options available to the urologist for managing secondary PUJO as well as providing some guidance on assessing factors that will influence management decisions. PMID- 24235792 TI - Continent urinary diversion. AB - We present a review on the current options for continent urinary diversion and their different indications on the basis of patient selection. In current clinical practice continent urinary diversion is being used world-wide in patients undergoing radical cystectomy and in severe cases of benign bladder pathologies. We also discuss the specific complications of continent urinary diversion and highlight the need to rigorously monitor these patients in the long term specifically in terms of their renal function and cancer recurrence. PMID- 24235793 TI - Metabolic complications of urinary intestinal diversion. AB - Patients with a urinary bladder malignancy or severe anatomical/functional bladder abnormalities may be candidates for urinary diversion at the time of cystectomy. Most urinary diversions are constructed from intestinal segments. Urological surgeons who perform urinary diversion surgery should be aware of the physiological and metabolic changes that can occur when intestinal segments are in direct contact with urine. The complications associated with urinary diversion are both acute and chronic. The most important factor associated with the development of metabolic complications following urinary diversion is the length of time that the urine is in contact with the bowel and the type of bowel segment used for urinary diversion. In this review, we describe the metabolic complications associated with urinary diversion, their characteristic clinical presentation, follow-up, and specific treatment. PMID- 24235794 TI - Reconstructing the lower urinary tract: The Mitrofanoff principle. AB - Since the original description of the trans-appendicular continent cystostomy by Mitrofanoff in 1980, a variety of techniques have been described for creating a continent catheterisable channel leading to the bladder, which avoids the native urethra. The Mitrofanoff principle involves the creation of a conduit going into a low pressure reservoir, which can emptied through clean intermittent catheterization through an easily accessible stoma. A variety of tissue segments have been used for creating the conduit, but the two popular options in current urological practice remain the appendix and Yang-Monti transverse ileal tube. The Mitrofanoff procedure has an early reoperation rate for bleeding, bowel obstruction, anastomotic leak or conduit breakdown of up to 8% and the most common long-term complication noted is stomal stenosis resulting in difficulty catheterizing the conduit. However, in both pediatric and adult setting, reports imply that the procedure is durable although it is associated with an overall re operation rate of up to 32% in contemporary series. Initial reports of laparoscopic and robotic-assisted Mitrofanoff procedures are encouraging, but long-term outcomes are still awaited. PMID- 24235795 TI - Augmentation cystoplasty: Contemporary indications, techniques and complications. AB - Augmentation cystoplasty (AC) has traditionally been used in the treatment of the low capacity, poorly compliant or refractory overactive bladder (OAB). The use of intravesical botulinum toxin and sacral neuromodulation in detrusor overactivity has reduced the number of AC performed for this indication. However, AC remains important in the pediatric and renal transplant setting and still remains a viable option for refractory OAB. Advances in surgical technique have seen the development of both laparoscopic and robotic augmentation cystoplasty. A variety of intestinal segments can be used although ileocystoplasty remains the most common performed procedure. Early complications include thromboembolism and mortality, whereas long-term problems include metabolic disturbance, bacteriuria, urinary tract stones, incontinence, perforation, the need for intermittent self catheterization and carcinoma. This article examines the contemporary indications, published results and possible future directions for augmentation cystoplasty. PMID- 24235797 TI - Bladder neck sparing in radical prostatectomy. AB - The role of a bladder neck sparing (BNS) technique in radical prostatectomy (RP) remains controversial. The potential advantages of improved functional recovery must be weighed against oncological outcomes. We performed a literature review to evaluate the current knowledge regarding oncological and functional outcomes of BNS and bladder neck reconstruction (BNr) in RP. A systematic literature review using on-line medical databases was performed. A total of 33 papers were identified evaluating the use of BNS in open, laparoscopic and robotic-assisted RP. The majority were retrospective case series, with only one prospective, randomised, blinded study identified. The majority of papers reported no significant difference in oncological outcomes using a BNS or BNr technique, regardless of the surgical technique employed. Quoted positive surgical margin rates ranged from 6% to 32%. Early urinary continence (UC) rates were ranged from 36% to 100% at 1 month, with long-term UC rate reported at 84-100% at 12 months if the bladder neck (BN) was spared. BNS has been shown to improve early return of UC and long-term UC without compromising oncological outcomes. Anastomotic stricture rate is also lower when using a BNS technique. PMID- 24235796 TI - Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction. AB - The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction. PMID- 24235798 TI - Infected inguinal hernia mesh presenting as pseudotumor of the bladder. AB - Pseudotumors are uncommon benign tumors considered as a reactive inflammatory lesion. We report a case of a 53-year-old male with a history of right laparoscopic hernia repair and now referred for suspected urachal cyst. Imaging investigations revealed an abdominal mass arising from the wall of the urinary bladder. During dissection, we found a tumor arising from the urinary bladder infiltrating the posterior wall of rectus muscles and further dissection revealed presence of the previously placed inguinal mesh. Postoperative histopathological examination revealed inflammatory pseudotumor. With only one comparable case described, an infected mesh presenting as pseudotumor of the bladder is extremely rare. PMID- 24235799 TI - Emphysematous pyelonephritis with IVC thrombus in new onset diabetes mellitus. AB - Emphysematous pyelonephritis (EPN) is a rapidly progressive necrotizing infection characterized by gas in the kidneys. We describe a 48-year-old woman, a newly diagnosed diabetic, who presented with clinical features of right sided pyelonephritis with hematuria of short duration. On further evaluation, she was diagnosed to have right sided EPN, with thrombus in the renal vein and inferior vena cava (IVC). She was managed conservatively with hydration, insulin, intravenous antibiotics, anticoagulants and ureteric stenting on the right side. On follow-up, the gas shadows resolved and the thrombus completely regressed. PMID- 24235800 TI - Fetus in bladder. AB - This is the first reported case of vesicouterine fistula presenting with a fully formed dead fetus in the urinary bladder. PMID- 24235801 TI - Migration of double J stent into the inferior vena cava and the right atrium. AB - Migration of a ureteric double J stent down into the bladder or up into the kidney is a well known complication. We recently encountered a case where the stent migrated into the vascular system following attempted ureteroscopy for a lower ureteric calculus. The patient required open surgical exploration for stent retrieval. PMID- 24235802 TI - Obstructive uropathy due to uretero-inguinal hernia: An uncommon occurrence. AB - Obstructive uropathy secondary to uretero-inguinal hernia is a rare phenomenon. Two types have been described-the rarer extraperitoneal type is frequently associated with other renal anomalies. Pre-operative diagnosis is essential in order to reduce the risk of ureteric injury intra-operatively. We describe one such case. PMID- 24235803 TI - Peripheral primitive neuroectodermal tumor of the adrenal gland: A rare entity. AB - Peripheral primitive neuroectodermal tumor (PNET) is an uncommon tumor and the overall incidence is 1% of all sarcomas. PNET of the adrenal gland is an even rarer entity. A 37-year-old female was evaluated for an episode of loin pain. Ultrasonography showed a large heterogenous left adrenal mass with internal echogenic components. Computed tomography did not show any fat density within to suggest a myelolipoma. Biopsy suggested a poorly differentiated neoplasm with a possibility of PNET of the adrenal gland. PMID- 24235804 TI - The superomedial thigh flap in scrotal reconstruction: Technical steps to improve cosmetic results. AB - The superomedial thigh flap is a reliable and easy method for scrotal reconstruction described in 1980 and infrequently reported in the literature since its description. We used it for four patients presenting scrotal defects after Fournier's gangrene with some technical modifications to improve the esthetic results and to facilitate the closure of the donor area. We describe the technical steps and the results. PMID- 24235805 TI - Redefining expanded criteria donor kidneys in the developing world. PMID- 24235806 TI - Manganese Detection with a Metal Catalyst Free Carbon Nanotube Electrode: Anodic versus Cathodic Stripping Voltammetry. AB - Anodic stripping voltammetry (ASV) and cathodic stripping voltammetry (CSV) were used to determine Mn concentration using metal catalyst free carbon nanotube (MCFCNT) electrodes and square wave stripping voltammetry (SWSV). The MCFCNTs are synthesized using a Carbo Thermal Carbide Conversion method which results in a material that does not contain residual transition metals. Detection limits of 120 nM and 93 nM were achieved for ASV and CSV, respectively, with a deposition time of 60 s. CSV was found to be better than ASV in Mn detection in many aspects, such as limit of detection and sensitivity. The CSV method was used in pond water matrix addition measurements. PMID- 24235807 TI - Zinc Detection in Serum by Anodic Stripping Voltammetry on Microfabricated Bismuth Electrodes. AB - Zinc (Zn) homeostasis is required for a functional immune system. Critically ill patients often exhibit decreased Zn serum concentrations and could potentially benefit from Zn supplementation as a therapeutic strategy. However, the conventional approaches to monitoring Zn are time consuming and costly. This work reports on detection of Zn by anodic stripping voltammetry (ASV) on bismuth electrodes in a microfabricated electrochemical cell. The working potential window of the electrodeposited bismuth film electrode was investigated by cyclic voltammetry, while square wave ASV was used for measuring Zn in acetate buffer and blood serum. Conditions critical to sensing, such as preconcentration potential, preconcentration time, and buffer pH, were optimized for Zn detection. The sensor was successfully calibrated with pH 6 acetate buffer in the physiologically-relevant range of 5 MUM to 50MUM Zn and exhibited well-defined and highly repeatable peaks. The sensor was used to demonstrate measurement of Zn in blood serum digested in HCl. The results of this work show that Zn detection in serum is possible with smaller sample volumes (MUL vs. MUL) and faster turnaround time (hours vs. days) as compared with the conventional spectroscopic methods. PMID- 24235808 TI - Seeking Models and Methods for Cultural Adaptation of Interventions: Commentary on the Special Section. PMID- 24235809 TI - Clinical characteristics and visual outcomes in infectious scleritis: a review. AB - Infection is a very important but rare cause of scleritis, occurring in about 5% 10% of all patients presenting with scleral inflammation. However, due to the similarity of its presentation, infectious scleritis is often initially managed as autoimmune, potentially further worsening its outcome. The overall visual outcome in infectious scleritis is generally worse than its autoimmune counterparts, perhaps because of the delay in diagnosis or because of the aggressive nature of associated microbes. Thus, there is a definite need for insight into the diagnostic approach and treatment options for this ocular disease process. Several studies and case reports have been published in recent years that have provided useful information regarding the presenting clinical features and etiologic microbial agents in infectious scleritis. This review summarizes the important findings in the literature that may aid in differentiating infectious scleritis from other etiologies, including predisposing factors, microbe-specific characteristics, diagnostic tools, treatment modalities, and outcomes. PMID- 24235810 TI - Clinical applications of optical coherence tomography in the posterior pole: the 2011 Jose Manuel Espino Lecture - Part I. AB - Optical coherence tomography (OCT) is now a standard of care in ophthalmology and is considered essential for the diagnosis and monitoring of many retinal diseases. One of the major advances obtained with OCT was the understanding of the pathophysiology of macular holes. Non-full-thickness macular holes have been revisited because high-resolution OCT images can detect a lamellar macular defect that is not always visible clinically, and surgery has been advocated by some authors. OCT can be valuable in determining the need for and/or timing of surgical intervention on epiretinal membranes or vitreomacular traction syndrome. In addition, we can use this technology as a predictive factor in the prognosis and follow-up of the most common posterior pole pathologies. PMID- 24235812 TI - Retinal thickness changes after phacoemulsification. AB - PURPOSE: To determine the effect of phacoemulsification on macular volume and thickness using spectral domain optical coherence tomography examinations. METHODS: Twenty-seven eyes of 27 subjects who underwent phacoemulsification were studied. All nine areas of the macula were examined by spectral domain optical coherence tomography preoperatively and 2 months postoperatively. Effective phacoemulsification time and absolute phacoemulsification time were also recorded. RESULTS: There were statistically significant differences in macular thickness between preoperative and postoperative spectral domain optical coherence tomography examinations in nine areas including macular volume. In the paracentral macular area, the thickness of three quadrants significantly increased (superior P=0.015; temporal P=0.001; and nasal P=0.023). Peripheral macular thickness also increased significantly in the superior (P=0.05) and temporal macular areas (P<0.001). The macular volume increased significantly after phacoemulsification (P<0.001). There were no correlations between absolute/effective phacoemulsification time and macular cellular structures (P>0.05), but a significant correlation (P=0.011) was found between absolute phacoemulsification time and change in macular volume. CONCLUSION: Macular thickness changes in the nasal, superior, and temporal quadrants of the paracentral area and the superior and temporal quadrants of the peripheral area, as well as macular volume, may be used as detailed biomarkers to measure the effects of intraocular pressure fluctuations and maneuvers in phacoemulsification intraocular surgeries. PMID- 24235811 TI - Clinical applications of optical coherence tomography in the posterior pole: the 2011 Jose Manuel Espino Lecture - Part II. AB - Optical coherence tomography (OCT) is a high-resolution, cross-sectional imaging technique that allows detailed assessment of retinal thickness and morphologic evaluation of the retinal layers. This technology has developed quickly over the past two decades. OCT imaging has rapidly been integrated into routine ophthalmic clinical practice and trials. It has complemented fluorescein angiography in many instances, especially in the diagnosis and management of retinal disorders, including diabetic macular edema and age-related macular degeneration. With OCT, the exact localization of pathologic features can be visualized in segmentation maps of the retina, and this has allowed OCT to be used to evaluate specific features that may serve as predictive factors in the prognosis and follow up of these pathologies. Therefore, it has become an important clinical and research tool for the diagnosis, follow up, treatment, and assessment of new treatment modalities for all diseases that affect the posterior pole of the eye. PMID- 24235813 TI - Neodymium:yttrium-aluminum garnet capsulotomy rates after combined cataract surgery with implantation of a 4% water content hydrophobic acrylic intraocular lens and vitrectomy. AB - BACKGROUND: The purpose of this study was to examine neodymium:yttrium-aluminum garnet (Nd:YAG) capsulotomy rates after combined cataract surgery with implantation of a three-piece 4% water content hydrophobic acrylic intraocular lens (X-70, Eternity(r)) and vitrectomy, and compare diabetic retinopathy with nondiabetic retinopathy. METHODS: Nd:YAG capsulotomy rates were evaluated for 72 eyes of 72 patients with diabetic retinopathy and 81 eyes of 81 patients with nondiabetic retinopathy (50 eyes with retinal detachment, 13 eyes with macular hole, nine eyes with epiretinal membrane, seven eyes with branch retinal vein occlusion, and two eyes with uveitis) who underwent combined cataract surgery and vitrectomy and implantation of X-70. RESULTS: Two years after combination surgery, four of 72 eyes (5.6%) in the diabetic retinopathy group and four of 81 eyes (5.0%) in the nondiabetic retinopathy group required Nd:YAG capsulotomies. Kaplan-Meier survival analysis showed no statistically significant differences between the two groups (P=0.30, Mantel-Cox log-rank test). CONCLUSION: The rate of Nd:YAG capsulotomy did not significantly differ between diabetic retinopathy and nondiabetic retinopathy after combined cataract surgery with implantation of the X-70 and vitrectomy. X-70 is an acceptable intraocular lens for patients undergoing combined cataract surgery and vitrectomy. PMID- 24235814 TI - Immunization of rabbits with synthetic peptides derived from a highly conserved beta-sheet epitope region underneath the receptor binding site of influenza A virus. AB - BACKGROUND: There is increasing concern about the speed with which health care providers can administer prophylaxis and treatment in an influenza pandemic. Generally, it takes several months to manufacture an influenza vaccine by propagation of the virus in chicken eggs or cultured cells. Newer, faster protocols for the production of vaccines that induce broad-spectrum immunity are therefore highly desirable. We previously developed human monoclonal antibody B-1 that shows broadly neutralizing activity against influenza A virus H3N2. B-1 recognizes an epitope region that includes an antiparallel beta-sheet structure underneath the receptor binding site of influenza hemagglutinin (HA). In this study, the efficacy of a synthetic peptide vaccine derived from this epitope region against influenza A was evaluated. MATERIALS AND METHODS: Two peptides were synthesized, the upper and lower peptides. These peptides comprise amino acid residues 167-187 and 225-241, respectively, of the B-1 epitope region of HA, which is involved in forming the beta-sheet structure. Both peptides were then coupled to keyhole limpet hemocyanin, and the peptides, alone or in combination, were used to immunize rabbits. The resulting antibody responses were examined by enzyme-linked immunosorbent assay. The upper peptide, but not the lower peptide, elicited antibodies that were reactive to HA. Interestingly, the use of both peptides together could elicit antibodies with a higher reactivity to HA than either peptide alone. The antibodies were found to react to HA at the N-terminus of the upper peptide, which is exposed at the surface of trimeric HA on influenza virions. DISCUSSION: The higher production of HA-reactive antibodies following immunization with both peptides suggests that the upper peptide forms the effective epitope structure in the binding state, and the lower peptide enhances the production of HA antibodies. This study could be the first step towards the development of pandemic viral vaccines that can be produced within short time periods. PMID- 24235815 TI - Heart rate reduction for 36 months with ivabradine reduces left ventricular mass in cardiac allograft recipients: a long-term follow-up study. AB - BACKGROUND: Due to graft denervation, sinus tachycardia is a common problem after heart transplantation, underlining the importance of heart rate control without peripheral effects. However, long-term data regarding the effects of ivabradine, a novel If channel antagonist, are limited in patients after heart transplantation. METHODS: In this follow-up analysis, the resting heart rate, left ventricular mass indexed to body surface area (LVMI), tolerability, and safety of ivabradine therapy were evaluated at baseline and after 36 months in 30 heart transplant recipients with symptomatic sinus tachycardia versus a matched control group. RESULTS: During the study period, ivabradine medication was stopped in three patients (10% of total). Further analysis was based on 27 patients with 36 months of drug intake. The mean patient age was 53.3+/-11.3 years and mean time after heart transplantation was 5.0+/-4.8 years. After 36 months, the mean ivabradine dose was 12.0+/-3.4 mg/day. Resting heart rate was reduced from 91.0+/-10.7 beats per minute before initiation of ivabradine therapy (ie, baseline) to 81.2+/-9.8 beats per minute at follow-up (P=0.0006). After 36 months of ivabradine therapy, a statistically significant reduction of LVMI was observed (104.3+/-22.7 g at baseline versus 93.4+/-18.4 g at follow-up, P=0.002). Hematologic, renal, and liver function parameters remained stable during ivabradine therapy. Except for a lower mycophenolate mofetil dose at follow-up (P=0.02), no statistically significant changes in immunosuppressive drug dosage or blood levels were detected. No phosphenes were observed during 36 months of ivabradine intake despite active inquiry. CONCLUSION: In line with previously published 12-month data, heart rate reduction with ivabradine remained effective and safe in chronic stable patients after heart transplantation, and also during 36-month long-term follow-up. Further, a significant reduction of LVMI was observed only during ivabradine therapy. Therefore, ivabradine may have a sustained long-term beneficial effect with regard to left ventricular remodeling in heart transplant patients. PMID- 24235816 TI - New and emerging treatments for symptomatic tardive dyskinesia. AB - The aim of this review is to assess new, emerging, and experimental treatment options for tardive dyskinesia (TD). The methods to obtain relevant studies for review included a MEDLINE search and a review of studies in English, along with checking reference lists of articles. The leading explanatory models of TD development include dopamine receptor supersensitivity, GABA depletion, cholinergic deficiency, neurotoxicity, oxidative stress, changes in synaptic plasticity, and defective neuroadaptive signaling. As such, a wide range of treatment options are available. To provide a complete summary of choices we review atypical antipsychotics along with resveratrol, botulinum toxin, Ginkgo biloba, tetrabenazine, clonazepam, melatonin, essential fatty acids, zonisamide, levetiracetam, branched-chain amino acids, drug combinations, and invasive surgical treatments. There is currently no US Food and Drug Administration approved treatment for TD; however, prudent use of atypical antipsychotics with routine monitoring remain the cornerstone of therapy, with experimental treatment options available for further management. PMID- 24235817 TI - Use of an interdisciplinary, participatory design approach to develop a usable patient self-assessment tool in atrial fibrillation. AB - After identifying that significant care gaps exist within the management of atrial fibrillation (AF), a patient-focused tool was developed to help patients better assess and manage their AF. This tool aims to provide education and awareness regarding the management of symptoms and stroke risk associated with AF, while engaging patients to identify if their condition is optimally managed and to become involved in their own care. An interdisciplinary group of health care providers and designers worked together in a participatory design approach to develop the tool with input from patients. Usability testing was completed with 22 patients of varying demographics to represent the characteristics of the patient population. The findings from usability testing interviews were used to further improve and develop the tool to improve ease of use. A physician-facing tool was also developed to help to explain the tool and provide a brief summary of the 2012 Canadian Cardiovascular Society atrial fibrillation guidelines. By incorporating patient input and human-centered design with the knowledge, experience, and medical expertise of health care providers, we have used an approach in developing the tool that tries to more effectively meet patients' needs. PMID- 24235819 TI - A study of patient experience and perception regarding postoperative pain management in Chinese hospitals. AB - BACKGROUND: This study aims to analyze the current status of postoperative pain management in the People's Republic of China's provincial-level hospitals, and the existing knowledge and opinions held by patients regarding these methods. METHODS: The 128 participants in this study were urology and hepatobiliary patients from three provincial-level hospitals in Hunan. The questionnaire assessing postoperative pain was designed using the typical pain assessment scales and pain management guidelines as references. RESULTS: 82.8% of study participants claimed that their postoperative pain was relieved within 3 days of their operations. However, while 91.4% of surveyed patients experienced moderate to severe pain, 51.6% received no treatment for their postoperative pain, and 14.9% complained that medical personnel failed to manage their pain. 20.2% were unsatisfied with their pain management, indicating that treatment did not meet their expectations. Furthermore, participants demonstrated a great misunderstanding of pain and analgesics, as 72.6% of patients were unfamiliar with morphine, 51.6% of patients believed only certain types of pain required management, and 18.5% refused to use morphine. CONCLUSION: In most Chinese provincial-level hospitals, current postoperative pain management methods are able to alleviate the pain experienced by the majority of patients, though pain assessment and therapy procedures are still not standardized. Furthermore, most patients lack a proper understanding of postoperative pain and analgesics. Therefore, pain management education for doctors and patients and their relatives should be implemented in order to improve the quality of postoperative pain management. PMID- 24235818 TI - Lanthanum carbonate for the control of hyperphosphatemia in chronic renal failure patients: a new oral powder formulation - safety, efficacy, and patient adherence. AB - Chronic kidney disease (CKD) is associated with very high mortality rates, mainly of cardiovascular origin. The retention of phosphate (P) and increased fibroblast growth factor-23 levels are common, even at early stages of CKD, due to disturbances in normal P homeostasis. Later, hyperphosphatemia appears, which has also been strongly associated with high mortality rates linked to P-mediated cardiovascular and procalcifying effects. Treatment guidelines for these patients continue to be poorly implemented, at least partially due to the lack of adherence to a P-restricted diet and P-binder therapy. Calcium-free P binders, such as lanthanum carbonate, have been associated with a decreased progression of vascular calcification, rendering them an important therapeutic alternative for these high cardiovascular risk CKD patients. Lanthanum carbonate has typically been available as chewable tablets, and the new presentation as an oral powder may provide a useful alternative in the therapeutic armamentarium. This powder is a tasteless, odorless, and colorless semisolid compound miscible with food. In a recent study in healthy individuals, the safety and efficacy of this novel form were evaluated, and it was concluded that it is well tolerated and pharmacodynamically equivalent to the chewable form. In the long run, individualization of preferences and treatments seems an achievable goal prior to final demonstration of improvements in hard outcomes in wide clinical trials in CKD patients. PMID- 24235820 TI - Factors associated with nonattendance at clinical medicine scheduled outpatient appointments in a university general hospital. AB - INTRODUCTION: Nonattendance at scheduled outpatient appointments for primary care is a major health care problem worldwide. Our aim was to estimate the prevalence of nonattendance at scheduled appointments for outpatients seeking primary care, to identify associated factors and build a model that predicts nonattendance at scheduled appointments. METHODS: A cohort study of adult patients, who had a scheduled outpatient appointment for primary care, was conducted between January 2010 and July 2011, at the Italian Hospital of Buenos Aires. We evaluated the history and characteristics of these patients, and their scheduling and attendance at appointments. Patients were divided into two groups: those who attended their scheduled appointments, and those who did not. We estimated the odds ratios (OR) and corresponding 95% confidence intervals (95% CI), and generated a predictive model for nonattendance, with logistic regression, using factors associated with lack of attendance, and those considered clinically relevant. Alternative models were compared using Akaike's Information Criterion. A generation cohort and a validation cohort were assigned randomly. RESULTS: Of 113,716 appointments included in the study, 25,687 were missed (22.7%; 95% CI: 22.34%-22.83%). We found a statistically significant association between nonattendance and age (OR: 0.99; 95% CI: 0.99-0.99), number of issues in the personal health record (OR: 0.98; 95% CI: 0.98-0.99), time between the request for and date of appointment (OR: 1; 95% CI: 1-1), history of nonattendance (OR: 1.07; 95% CI: 1.07-1.07), appointment scheduled later than 4 pm (OR: 1.30; 95% CI: 1.24-1.35), and specific days of the week (OR: 1.00; 95% CI: 1.06-1.1). The predictive model for nonattendance included characteristics of the patient requesting the appointment, the appointment request, and the actual appointment date. The area under the receiver operating characteristic curve of the predictive model in the generation cohort was 0.892 (95% CI: 0.890-0.894). CONCLUSION: Evidence related to patient characteristics, and the identification of appointments with a higher likelihood of nonattendance, should promote guided strategies to reduce the rate of nonattendance, as well as to future research on this topic. The use of predictive models could further guide management strategies to reduce the rate of nonattendance. PMID- 24235821 TI - The aging lung. AB - There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly. PMID- 24235823 TI - Chronic obstructive pulmonary disease exacerbation frequency and severity. PMID- 24235822 TI - Pathophysiology and clinical implications of pulmonary arterial enlargement in COPD. AB - Chronic obstructive pulmonary disease (COPD) is a complex condition defined by progressive airflow limitation in response to noxious stimuli, inflammation, and vascular changes. COPD exacerbations are critical events in the natural history of the disease, accounting for the majority of disease burden, cost, and mortality. Pulmonary vascular disease is an important risk factor for disease progression and exacerbation risk. Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A) ratio >1, has been evaluated as a marker of pulmonary vascular disease. The PA:A ratio can be measured reliably independent of electrocardiographic gating or the use of contrast, and in healthy patients a PA:A ratio >0.9 is considered to be abnormal. The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease. In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events. Future studies should be aimed at determining the stability of the metric over time and evaluating the utility of the PA:A ratio in guiding specific therapies. PMID- 24235824 TI - Home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized clinical trial. AB - INTRODUCTION: Pulmonary rehabilitation (PR) is a multidisciplinary program of care for patients with chronic obstructive pulmonary disease (COPD) with the goal of improving the functional capacity and quality of life, as well as maintaining the clinical stability of COPD sufferers. However, not all patients are available for such a program despite discomfort with their condition. The aim of this study was to evaluate the effects of a home-based PR (HBPR) program on functional ability, quality of life, and respiratory muscle strength and endurance. PATIENTS AND METHODS: Patients with COPD according to the Global Initiative of Chronic Obstructive Lung Disease were randomized (double-blind) into two groups. One group performed a protocol at home with aerobic and muscle strength exercises and was called the intervention group; the other group received only instructions to perform breathing and stretching exercises, characterizing it as the control group (CG). We assessed the following variables at baseline and 2 months: exercise tolerance (incremental shuttle walk test and upper limb test), respiratory muscle (strength and endurance test), and health-related quality of life (Airways Questionnaire 20). RESULTS: There were no significant changes after the intervention in either of the two groups in exercise tolerance and quality of life. However, the intervention group had improved respiratory endurance compared with the CG, while the CG presented a decrease in the load sustained by the respiratory muscles after the HBPR. CONCLUSION: A program of HBPR with biweekly supervision (although not enough to provide significant improvements in physical capacity or quality of life) played an important role in maintaining the stability of the clinical features of patients with COPD; the patients had no worsening of symptoms during the intervention period according to the daily log. PMID- 24235825 TI - The impact of PEGylation patterns on the in vivo biodistribution of mixed shell micelles. AB - Polyethylene glycol (PEG)-ylation is a widely used strategy to fabricate nanocarriers with a long blood circulation time. Further elaboration of the contribution of the surface PEGylation pattern to biodistribution is highly desirable. We fabricated a series of polyion complex (PIC) micelles PEGylated with different ratios (PEG2k and PEG550). The plasma protein adsorption, murine macrophage uptake, and in vivo biodistribution with iodine-125 as the tracer were systematically studied to elucidate the impact of PEGylation patterns on the biodistribution of micelles. We demonstrated that the PEGylated micelles with short hydrophilic PEG chains mixed on the surface were cleared quickly by the reticuloendothelial system (RES), and the single PEG2k PEGylated micelles could efficiently prolong the blood circulation time and increase their deposition in tumor sites. The present study extends the understanding of the PEGylation strategy to further advance the development of ideal nanocarriers for drug delivery and imaging applications. PMID- 24235826 TI - Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics. AB - BACKGROUND: The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs) using a cell free extract of Acinetobacter spp. and evaluate their antibacterial activity. METHODS: Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC) breakpoints of the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8-12 nm were obtained with 0.7 mM silver nitrate at 70 degrees C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm) observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter aerogenes, a 3.8-fold increase in inhibition zone area was observed after the addition of AgNPs with vancomycin. Reduction in MIC and minimum bactericidal concentration was observed on exposure of AgNPs with antibiotics. Interestingly, multidrug-resistant A. baumannii was highly sensitized in the presence of AgNPs and became susceptible to antibiotics except cephalosporins. Similarly, the vancomycin-resistant strain of Streptococcus mutans was also found to be susceptible to antibiotic treatment when AgNPs were added. These biogenic AgNPs showed significant synergistic activity on the beta lactam class of antibiotics. CONCLUSION: This is the first report of synthesis of AgNPs using A. calcoaceticus LRVP54 and their significant synergistic activity with antibiotics resulting in increased susceptibility of multidrug-resistant bacteria evaluated as per MIC breakpoints of the CLSI standard. PMID- 24235827 TI - Fate of paclitaxel lipid nanocapsules in intestinal mucus in view of their oral delivery. AB - The bioavailability of paclitaxel (Ptx) has previously been improved via its encapsulation in lipid nanocapsules (LNCs). In this work, the interactions between LNCs and intestinal mucus are studied because they are viewed as an important barrier to successful oral delivery. The rheological properties of different batches of pig intestinal mucus were studied under different conditions (the effect of hydration and the presence of LNCs). Fluorescence resonance energy transfer (FRET) was used to study the stability of LNCs in mucus at 37 degrees C for at least 3 hours. Diffusion through 223, 446, and 893 MUm mucus layers of 8.4, 16.8, and 42 MUg/mL Ptx formulated as Taxol(r) (Bristol-Myers Squibb, Rueil Malmaison, France) or encapsulated in LNCs (Ptx-LNCs) were investigated. The effect of the size of the LNCs on their diffusion was also investigated (range, 25-110 nm in diameter). Mucus behaves as a non-Newtonian gel with rheofluidifying properties and a flow threshold. The viscous (G") and elastic (G') moduli and flow threshold of the two mucus batches varied with water content, but G' remained below G". LNCs had no effect on mucus viscosity and flow threshold. The FRET efficiency remained at 78% after 3 hours. Because the destruction of the LNCs would lead to a FRET efficiency below 25%, these results suggest only a slight modification of LNCs after their contact with mucus. The diffusion of Taxol(r) and Ptx-LNCs in mucus decreases if the mucus layer is thicker. Interestingly, the apparent permeability across mucus is higher for Ptx-LNCs than for Taxol(r) for drug concentrations of 16.8 and 42 MUg/mL Ptx (P<0.05). The diffusion of Ptx-LNCs through mucus is not size-dependent. This study shows that LNCs are stable in mucus, do not change mucus rheological properties, and improve Ptx diffusion at low concentrations, thus making these systems good candidates for Ptx oral delivery. The study of the physicochemical interaction between the LNC surface and its diffusion in mucus is now envisioned. PMID- 24235828 TI - Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3. AB - The interaction between silver nanoparticles and viruses is attracting great interest due to the potential antiviral activity of these particles, and is the subject of much research effort in the treatment of infectious diseases. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with herpes simplex virus types 1 and 2 and with human parainfluenza virus type 3. We show that production of silver nanoparticles from different fungi is feasible, and their antiviral activity is dependent on the production system used. Silver nanoparticles are capable of reducing viral infectivity, probably by blocking interaction of the virus with the cell, which might depend on the size and zeta potential of the silver nanoparticles. Smaller-sized nanoparticles were able to inhibit the infectivity of the viruses analyzed. PMID- 24235829 TI - Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star shaped poly(lactic-co-glycolic acid). AB - BACKGROUND: Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. METHODS: A new series of six-arm star shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles' encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). RESULTS: The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40 degrees C-50 degrees C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4+/-6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from linear poly(lactic-co glycolic acid). In the cytostatic study, the 6-s-PLGA-PTX-NPs and L-PLGA-PTX-NPs were found to have a similar antiproliferative effect, which indicates durable efficacy due to the slower release of the PTX when loaded in 6-s-PLGA. CONCLUSION: The results suggest that 6-s-PLGA may be promising for application in PTX delivery to enhance sustained antiproliferative therapy. PMID- 24235830 TI - Synthesis and characterization of surface-enhanced Raman-scattered gold nanoparticles. AB - In this paper, we report a simple, rapid, and robust method to synthesize surface enhanced Raman-scattered gold nanoparticles (GNPs) based on green chemistry. Vitis vinifera L. extract was used to synthesize noncytotoxic Raman-active GNPs. These GNPs were characterized by ultraviolet-visible spectroscopy, dynamic light scattering, Fourier-transform infrared (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy. The characteristic surface plasmon-resonance band at ~ 528 nm is indicative of spherical particles, and this was confirmed by TEM. The N-H and C-O stretches in FTIR spectroscopy indicated the presence of protein molecules. The predominant XRD plane at (111) and (200) indicated the crystalline nature and purity of GNPs. GNPs were stable in the buffers used for biological studies, and exhibited no cytotoxicity in noncancerous MIO-M1 (Muller glial) and MDA-MB-453 (breast cancer) cell lines. The GNPs exhibited Raman spectral peaks at 570, 788, and 1,102 cm(-1). These new GNPs have potential applications in cancer diagnosis, therapy, and ultrasensitive biomarker detection. PMID- 24235831 TI - Antitumor activity of tripterine via cell-penetrating peptide-coated nanostructured lipid carriers in a prostate cancer model. AB - BACKGROUND: The purpose of this study was to evaluate the antitumor effect of cell-penetrating peptide-coated tripterine-loaded nanostructured lipid carriers (CT-NLC) on prostate tumor cells in vitro and in vivo. METHODS: CT-NLC were developed to improve the hydrophilicity of tripterine. The antiproliferative effects of CT-NLC, tripterine-loaded nanostructured lipid carriers (T-NLC), and free tripterine in a human prostatic carcinoma cell line (PC-3) and a mouse prostate carcinoma cell line (RM-1) were evaluated using an MTT assay. The advantage of CT-NLC over T-NLC and free tripterine with regard to antitumor activity in vivo was evaluated in a prostate tumor-bearing mouse model. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content was investigated by enzyme-linked immunosorbent assay to determine the effect of CT NLC, T-NLC, and free tripterine on immune responses. Histologic and TUNEL assays were carried out to investigate the mechanisms of tumor necrosis and apoptosis. RESULTS: CT-NLC, T-NLC, and free tripterine showed high antiproliferative activity in a dose-dependent manner, with an IC50 of 0.60, 0.81, and 1.02 MUg/mL in the PC-3 cell line and 0.41, 0.54, and 0.89 MUg/mL in the RM-1 cell line after 36 hours. In vivo, the tumor inhibition rates for cyclophosphamide, high-dose (4 mg/kg) and low-dose (2 mg/kg) tripterine, high-dose (4 mg/kg) and low-dose (2 mg/kg) T-NLC, high-dose (4 mg/kg) and low-dose (2 mg/kg) CT-NLC were 76.51%, 37.07%, 29.53%, 63.56%, 48.25%, 72.68%, and 54.50%, respectively, showing a dose dependent pattern. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content after treatment with CT-NLC and T-NLC was significantly higher than that of high-dose tripterine. Moreover, CT-NLC showed the expected advantage of inducing necrosis and apoptosis in prostate tumor cells. CONCLUSION: CT-NLC noticeably enhanced antitumor activity in vitro and in vivo and showed dramatically improved cytotoxicity in normal cells in comparison with free tripterine. In summary, CT-NLC could be used as a promising drug delivery system for the treatment of prostate cancer. PMID- 24235832 TI - Inhibition of choriocarcinoma by Fe3O4-dextran-anti-beta-human chorionic gonadotropin nanoparticles containing antisense oligodeoxynucleotide of heparanase. AB - OBJECTIVE: To observe the influence of Fe3O4-dextran-anti-beta-human chorionic gonadotropin (HCG) carrying heparanase (Hpa) antisense oligodeoxynucleotide (ASODN), via the invasion, proliferation, and Hpa expression of JEG-3 cell lines and inhibitory effect of transplanted choriocarcinoma tumor growth. METHODS: The different abilities of invasion and proliferation between transfected JEG-3 and untransfected JEG-3 were measured by Matrigel invasion assay and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in vitro. The effect of Hpa ASODN transfection on the expression of Hpa mRNA and protein was measured by reverse-transcription polymerase chain reaction and Western blot. The transplanted choriocarcinoma tumors were taken out to calculate the inhibitory effect on tumor growth of Hpa ASODN. RESULTS: IN THIS STUDY, WE FOUND THAT: (1) the invasive ability of JEG-3 cells was inhibited sufficiently (P < 0.05) after JEG-3 cells were transfected by Fe3O4-dextran-anti-betaHCG carrying Hpa ASODN; (2) after JEG-3 cells were transfected by Fe3O4-dextran-anti-betaHCG carrying Hpa ASODN at 48 and 72 hours, the proliferative ability of JEG-3 cells was inhibited sufficiently (P < 0.05); (3) the expression of Hpa mRNA and protein in JEG-3 cells was inhibited efficiently after JEG-3 cells were transfected by Fe3O4 dextran-anti-betaHCG carrying Hpa ASODN (P < 0.05); and (4) Fe3O4-dextran-anti betaHCG carrying Hpa ASODN had an inhibitory effect on the transplanted choriocarcinoma tumor growth (P < 0.05) and was harmless on nude mice. CONCLUSION: Fe3O4-dextran-anti-betaHCG carrying Hpa ASODN weakened the invasive and proliferative ability of choriocarcinoma, with a significant inhibitory effect on the transplanted choriocarcinoma tumor. Therefore, Fe3O4-dextran-anti betaHCG carrying Hpa ASODN is an effective gene therapy, and Fe3O4-dextran-anti betaHCG nanoparticles are a harmless and effective gene vector. PMID- 24235833 TI - Identification of common predictors of surgical outcomes for epilepsy surgery. AB - Although epilepsy surgery is an effective treatment for patients with drug resistant epilepsy, surgical outcomes vary across patient groups and studies. Identification of reliable prognostic factors for surgical outcome is important for outcome research. In this study, recent systematic reviews and meta-analyses on prediction of seizure outcome have been analyzed, and common predictors of seizure outcome or unrelated factors for temporal lobe epilepsy (TLE), lesional extratemporal lobe epilepsy (ETLE), and tuberous sclerosis complex have been identified. Clinical factors such as lesional epilepsy, abnormal magnetic resonance imaging, partial seizures, and complete resection were found to be common positive predictors, and factors such as nonlesional epilepsy, poorly defined and localized epileptic focus, generalized seizures, and incomplete resection are common negative predictors, while factors such as age at surgery and side of surgery are unrelated to seizure outcome for TLE and lesional ETLE. In addition, diagnostic neuroimaging and resection are among the most important predictors of seizure outcome. However, common predictors of seizure outcome could not be identified in nonlesional ETLE because no predictors were found to be significant in adult patients (by meta-analysis), and outcome prediction is difficult in this case. Meta-analysis of other outcomes, such as neuropsychologic outcomes, is rare due to lack of evaluation standards. Further studies on identification of reliable predictors of surgical outcomes are needed. PMID- 24235835 TI - Quality of Web-based information on obsessive compulsive disorder. AB - BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score >=16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. PRACTICAL IMPLICATIONS: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web. PMID- 24235834 TI - The role of the serotonergic system in suicidal behavior. AB - Serotonin is a widely investigated neurotransmitter in several psychopathologies, including suicidal behavior (SB); however, its role extends to several physiological functions involving the nervous system, as well as the gastrointestinal and cardiovascular systems. This review summarizes recent research into ten serotonergic genes related to SB. These genes - TPH1, TPH2, SLC6A4, SLC18A2, HTR1A, HTR1B, HTR2A, DDC, MAOA, and MAOB - encode proteins that are vital to serotonergic function: tryptophan hydroxylase; the serotonin transporter 5-HTT; the vesicular transporter VMAT2; the HTR1A, HTR1B, and HTR2A receptors; the L-amino acid decarboxylase; and the monoamine oxidases. This review employed a systematic search strategy and a narrative research methodology to disseminate the current literature investigating the link between SB and serotonin. PMID- 24235837 TI - Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses. AB - BACKGROUND: A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI) from either oral olanzapine (OLZ) or other antipsychotics (non-OLZ). METHODS: Post hoc analyses were done based on two randomized studies (one short-term, one long-term) conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8 week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. RESULTS: These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ) from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ) from the long term study. Kaplan-Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209) or long-term study (P=0.448). Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198) or long-term (57.1% versus 47.8% respectively; P=0.238) studies. In the short-term study, no significant differences were detected between the patient groups in mean change in Positive and Negative Syndrome Scale (PANSS) total score (-13.4 OLZ versus -20.8 non-OLZ; P=0.166). In the long-term study, mean change in PANSS total score (3.9 OLZ versus -3.6 non-OLZ; P=0.008) was significantly different between the non-OLZ and OLZ groups. Rates of treatment-emergent adverse events were similar in OLZ and non-OLZ groups per study. CONCLUSION: These post hoc analyses suggest that no significant differences in clinical effectiveness were seen after switching from non-OLZ or OLZ to OLAI. However, these findings should be interpreted with care, due to small sample sizes and differences in patients' clinical profiles. PMID- 24235836 TI - Risk factors for fatal and nonfatal repetition of suicide attempts: a literature review. AB - OBJECTIVES: This review aimed to identify the evidence for predictors of repetition of suicide attempts, and more specifically for subsequent completed suicide. METHODS: We conducted a literature search of PubMed and Embase between January 1, 1991 and December 31, 2009, and we excluded studies investigating only special populations (eg, male and female only, children and adolescents, elderly, a specific psychiatric disorder) and studies with sample size fewer than 50 patients. RESULTS: The strongest predictor of a repeated attempt is a previous attempt, followed by being a victim of sexual abuse, poor global functioning, having a psychiatric disorder, being on psychiatric treatment, depression, anxiety, and alcohol abuse or dependence. For other variables examined (Caucasian ethnicity, having a criminal record, having any mood disorders, bad family environment, and impulsivity) there are indications for a putative correlation as well. For completed suicide, the strongest predictors are older age, suicide ideation, and history of suicide attempt. Living alone, male sex, and alcohol abuse are weakly predictive with a positive correlation (but sustained by very scarce data) for poor impulsivity and a somatic diagnosis. CONCLUSION: It is difficult to find predictors for repetition of nonfatal suicide attempts, and even more difficult to identify predictors of completed suicide. Suicide ideation and alcohol or substance abuse/dependence, which are, along with depression, the most consistent predictors for initial nonfatal attempt and suicide, are not consistently reported to be very strong predictors for nonfatal repetition. PMID- 24235838 TI - Developments in the treatment of moderate to severe ulcerative colitis: focus on adalimumab. AB - In selected patients with moderate to severe active ulcerative colitis who have failed to respond or are poorly responsive to standard pharmacologic forms of treatment with corticosteroids and immunosuppressive agents, therapy with a biological agent may be considered. While infliximab is an established tumor necrosis factor blocker and has a longer history of clinical use, adalimumab is an alternative in the same class and may be employed as an initial biological agent, if indicated for treatment of the disease. Adalimumab may have special appeal to stable users able to self-inject in a home setting rather than a centralized infusion center. Short-term adverse effects have been limited, but long-term adverse events can be serious and remain less well defined. Recently, another agent, subcutaneous golimumab, has also been reported to induce and maintain clinical response and remission in clinical trials, but a large experience has not been accumulated to date in clinical practice. In the future, other biological agents with novel and distinct mechanisms of therapeutic action may become available. PMID- 24235839 TI - Titration of amlodipine to higher doses: a comparison of Asian and Western experience. AB - In this retrospective analysis, data pooled from two Phase III/IV open-label Asian studies were used to quantify the additional blood pressure efficacy achieved when titrating amlodipine from 5 mg to 10 mg in mild/moderate hypertensive patients, and compared to data pooled from three Western studies. The primary efficacy end point was the change from baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) to the specified time point (4-8 weeks, depending on the trial). For the Asian analysis (n=174), both mean SBP and DBP were significantly decreased at the final visit (SBP -13.3 mmHg, 95% confidence interval [CI] -15.5 to -11.0; DBP -9.2 mmHg, 95% CI -10.6 to -7.8; both P<0.0001). These results were similar to the Western analysis (n=369; SBP 11.5 mmHg, 95% CI -13.1 to -10.0; DBP -6.3, 95% CI -7.1 to -5.5; both P<0.0001). In summary, titration of amlodipine from 5 mg to 10 mg significantly decreased both SBP and DBP in Asian patients with mild-to-moderate hypertension. PMID- 24235840 TI - Diagnostic efficacy of computed tomography-guided transthoracic needle aspiration and biopsy in patients with pulmonary disease. AB - BACKGROUND: Computed tomography-guided transthoracic needle aspiration (TTNA) and biopsy (TTNB) is a well established, safe, and rapid method of reaching a definitive diagnosis for most thoracic lesions. The present study aimed to determine the roles of TTNA and TTNB in the diagnosis of pulmonary diseases and to compare the results using these two techniques. METHODS: TTNB and TTNA were performed in 105 patients admitted to our clinic due to peripheral pulmonary lesions between May 2005 and November 2007. Needle biopsies were performed using 18-gauge Tru-Cut(r) biopsy needles and aspirations was performed using 18-20-22 gauge Chiba needles. RESULTS: Malignant lesions diagnosed by TTNB were non-small cell lung carcinoma (51 patients, 73%), small cell lung carcinoma (nine patients, 13%), malignant tissue (three patients, 5%), lymphoma (two patients, 3%), thymoma (two patients, 3%), plasmacytoma (one patient, 1%), rhabdomyosarcoma (one patient, 1%), and metastasis (one patient, 1%). The malignant lesions diagnosed by TTNA were non-small cell lung carcinoma in eleven patients (92%) and malignant tissue in one patient (8%). Three (100%) of the benign lesions diagnosed by TTNB were granulomas and two (100%) benign lesions diagnosed by TTNA were infarctions. When the diagnostic value of TTNB and TTNA was compared, TTNB was significantly superior. Malignant lesions were identified in 70 (84%) and benign lesions were identified in three (4%) of the 83 patients in the TTNB group. Ten (12%) patients in the TTNB group could not be diagnosed. Malignant lesions were found in 12 (55%) and benign lesions were found in two (9%) of the 22 patients in the TTNA group. Negative results were obtained in eight (36%) patients. The diagnostic sensitivity, specificity, and accuracy of TTNB was calculated to be 92%, 100%, and 93%, respectively (Table 5). The diagnostic sensitivity, specificity, and accuracy of TTNA was 78%, 100%, and 82%, respectively. TTNB had a sensitivity of 92% (70/76) in malignant cases and 100% (3/3) in benign cases, while the sensitivity of TTNA in malignant and benign cases was 75% (3/4) and 67% (2/3), respectively. CONCLUSION: TTNB is a safe and easy procedure which provides a highly accurate diagnosis of benign and malignant lung lesions without causing a significant increase in complication rates. PMID- 24235841 TI - Successful treatment of paraganglioma with sorafenib: a case report and brief review of the literature. AB - INTRODUCTION: To date, no effective systemic therapies have been made available for paraganglioma. However, multiple mutations in susceptibility genes have been identified that are potential targets for sorafenib, an oral multitargeted tyrosine-kinase inhibitor. CASE PRESENTATION: We report the case of a 69-year-old Chinese man with mediastinal paraganglioma that had metastasized to the bone. The paraganglioma responded to sorafenib, a novel multi-tyrosine kinase inhibitor that targets angiogenesis, the Raf-kinase pathway, the platelet-derived growth factor Ret, and c-Kit. The patient was diagnosed as having paraganglioma after biopsy of the mediastinal mass. We first treated the patient with radiotherapy. Then he tolerated an etoposide-and-cisplatin chemotherapy regimen. Subsequently, he received 6 months of maintenance treatment with sorafenib (400 mg twice daily). A dramatic reduction in tumor volume was observed. At present, the patient has achieved a partial response, and his clinical status remains unchanged. CONCLUSION: We suggest that sorafenib should be further investigated in the management of patients with paraganglioma. PMID- 24235842 TI - Transcatheter arterial embolization promotes liver tumor metastasis by increasing the population of circulating tumor cells. AB - Transcatheter arterial embolization (TAE) is widely used as an effective palliative treatment for hepatocellular carcinoma (HCC), and can prolong survival time. However, the high incidence of tumor recurrence and metastasis after TAE is still a major problem. Recent studies demonstrated that circulating tumor cells (CTCs) contribute to tumor metastasis. In this study, we tried to clarify whether the residual HCC after TAE can increase metastasis by increasing the number of CTCs. An orthotopic liver tumor model in the Buffalo rat was established using green fluorescent protein (GFP)-transfected HCC cell line, McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent TAE treatment from the gastroduodenal artery. Iodized oil or saline was injected intra-arterially. Blood samples were taken on day 0, 1, 3, 7, 14, and 21 for detection of CTCs after TAE treatment. We analyzed the number of CTCs and assessed the metastatic potential of surviving tumor cells in rats between TAE and control groups. Our results demonstrated that the metastatic colonies in the lung were significantly increased by TAE treatment. The number of CTCs was also significantly increased by TAE treatment from day 7 to day 21. The expression of hypoxia-inducible factor (HIF)-1alpha and epithelial-mesenchymal transition (EMT) marker proteins (N cadherin and vimentin) was upregulated, but E-cadherin was downregulated after TAE treatment. In conclusion, the metastatic potential of residual HCC can be induced by TAE treatment in a rat liver tumor model, which involves the acquisition of EMT features and an increased number of CTCs. PMID- 24235844 TI - Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial. AB - OBJECTIVE: To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer. METHODS: This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy. RESULTS: There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50 70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405). CONCLUSION: Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer. EGFR overexpression was more common than previously reported. OS was higher after combined therapy than after historical control radiotherapy alone. Further studies are required to confirm the therapeutic efficacy of nimotuzumab in esophageal cancer. PMID- 24235843 TI - Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers. AB - Toll-like receptor 4 (TLR-4) is well known for its host innate immunity. Despite the fact that TLR-4 activation confers antitumor responses; emerging evidence suggests that TLR-4 is associated with tumor development and progression. It is now clear that overactivation of TLR-4, through various immune mediators, may cause immune response dysfunction, resulting in tumorigenesis. Different cancers could have different extents of TLR-4 involvement during tumorigenesis or tumor progression. In this review, we focus on infection- and inflammation-related TLR 4 activation in noncancer and cancer cells, as well as on the current evidence about the role of TLR-4 in ten of the most common cancers, viz, head and neck cancer, lung cancer, gastrointestinal cancer, liver cancer, pancreatic cancer, skin cancer, breast cancer, ovarian cancer, cervical cancer, and prostate cancer. PMID- 24235845 TI - Cancer stem cell-related marker expression in lung adenocarcinoma and relevance of histologic subtypes based on IASLC/ATS/ERS classification. AB - BACKGROUND: The cancer stem cell (CSC) theory has been proposed to explain tumor heterogeneity and the carcinogenesis of solid tumors. The aim of this study was to clarify the clinical role of CSC-related markers in patients with lung adenocarcinoma and to determine whether each CSC-related marker expression correlates with the histologic subtyping proposed by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) classifications. METHODS: We reviewed data for all 103 patients in whom complete resection of adenocarcinoma had been performed. Expression of CSC-related markers, ie, aldehyde dehydrogenase 1A1 (ALDH1A1), aldo-keto reductase 1C family member 1 (AK1C1), and 1C family member 3 (AK1C3), was examined using immunostaining on whole-mount tissue slides, and the tumors were reclassified according to the IASLC/ATS/ERS classification. RESULTS: ALDH1A1 expression was observed in 66.0% of tumors, AK1C1 in 62.7%, and AK1C3 in 86.1%. Immunoreactivities with the frequency of mean expression of ALDH1A1 in papillary predominant adenocarcinoma were significantly higher than those of solid predominant adenocarcinoma (P<0.05). Papillary predominant adenocarcinoma had significantly lower expression of AK1C1 when compared with noninvasive or solid predominant adenocarcinomas (P<0.05). On multivariate analysis, larger tumor size (hazards ratio 1.899, P=0.044), lymph node metastasis (hazards ratio 2.702, P=0.005), and low expression of ALDH1A1 (hazards ratio 3.218, P<0.001) were shown to be independently associated with an unfavorable prognosis. CONCLUSION: Immunohistochemistry of ALDH1A1 expression is strongly associated with prognosis. Expression of each CSC-related marker varies according to subtype, suggesting that a comprehensive histologic subtyping approach in the IASLC/ATS/ERS classification provides new molecular biology insights into the genesis of lung adenocarcinoma according to CSC theory. PMID- 24235846 TI - Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women. AB - OBJECTIVE: Poor adherence to chronic medications is common and compromises medication effectiveness. We sought to describe longitudinal patterns of osteoporosis medication use. STUDY DESIGN: This was a retrospective observational cohort study using 2005-2009 data from a large, commercially insured population. METHODS: Patients were women aged >=55 years initiating osteoporosis therapy who had a >=12-month (baseline) period with no osteoporosis therapy claims preceding initiation, and >=24 months follow-up after therapy initiation. Discontinuation was defined as a gap >60 days (varied in sensitivity analyses) in prescription claims. Reinitiation was defined as a prescription claim for the same or different osteoporosis therapy following the therapy gap. Discontinuation and reinitiation patterns were described using Kaplan-Meier analysis. Multivariable Cox regression assessed the impact of baseline factors on reinitiation. RESULTS: Of the 92,839 patients, 45%, 58%, and 70% discontinued therapy at 6, 12, and 24 months, respectively, following initiation. Of the discontinuers, 46% reinitiated therapy, with the majority doing so within 6 months of discontinuation. Women were less likely to reinitiate therapy if they were older (P < 0.0001) or were hospitalized during baseline (P = 0.0007). Women who discontinued treatment early (<6 months) following initiation were less likely to reinitiate (P < 0.0001) and remained on therapy for shorter periods following reinitiation. Depending on the available observation time, the median time on therapy following reinitiation was 58-193 days. Study findings did not change appreciably in sensitivity analyses. CONCLUSION: Many patients stop and restart treatment for osteoporosis. A better understanding of determinants of treatment stopping and restarting could inform adherence improvement efforts. PMID- 24235847 TI - The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective. AB - OBJECTIVES: The objectives of our large observational study were to describe the prevalence of cardiac and noncardiac comorbidities in a community-based population of patients hospitalized with acute myocardial infarction (AMI) at all medical centers in central Massachusetts, and to examine whether multiple comorbidities were associated with in-hospital death rates and hospital length of stay. METHODS: The study sample consisted of 2,972 patients hospitalized with AMI at all eleven greater Worcester medical centers in central Massachusetts during the three study years of 2003, 2005, and 2007. RESULTS: The average age of this hospitalized population was 71 years, 55% were men, 93% were Caucasian, and approximately one third had developed an ST segment elevation AMI during the years under study. Hypertension (75%) was the most common cardiac condition identified in patients hospitalized with AMI whereas renal disease (22%) was the most common noncardiac comorbidity diagnosed in this study population. Approximately one in every four hospitalized patients had any four or more of the seven cardiac conditions examined, while one in 13 had any three or more of the five noncardiac conditions studied. Patients with four or more cardiac comorbidities were more than twice as likely to have died during hospitalization and have a prolonged hospital length of stay, compared to those without any cardiac comorbidities. Patients with three or more noncardiac comorbidities had markedly increased odds of dying during hospitalization and having a prolonged hospital stay compared to those with no noncardiac comorbidities previously diagnosed. CONCLUSION: Our findings highlight the need for additional contemporary data to improve the short-term outcomes of patients hospitalized with AMI and multiple concurrent medical illnesses. PMID- 24235848 TI - Effectiveness of a modified version of the applied relaxation technique in treatment of perimenopausal and postmenopausal symptoms. AB - BACKGROUND: Awareness of the risks associated with hormone therapy for menopausal symptoms has sparked a global decline in this treatment. Alternative treatments to relieve menopausal symptoms are therefore required. The applied relaxation (AR) technique has proven to be successful for symptom amelioration, but requires participation in 12 weekly classes. The purpose of this study was to determine the effectiveness of a modified relaxation version (MR) of AR for treatment of hot flashes, night sweats, and sleep disturbances. METHODS: We conducted a12 week, randomized, parallel, open-label, controlled trial in perimenopausal and postmenopausal women visiting the menopausal clinic. Participants were randomly assigned to an MR or AR group. The MR group (n=36) received a single session of (MR) training and the AR group (n=35) received conventional 12-week training. Participants were instructed to practice the techniques daily at home for 12 weeks. The main outcome was the measure on the severity scale and frequency of hot flashes, night sweats, and sleep disturbances. RESULTS: All participants completed the study. Total severity scores in both groups decreased after 12 weeks, but there was no difference between the groups (P=0.93). The severity score for hot flashes in the MR group decreased more than in the AR group (P=0.02). The severity scores for night sweats and sleep disturbances decreased in both groups. The frequency of hot flashes, night sweats, and sleep disturbances were also decreased in both groups. CONCLUSION: A shorter, modified version of the AR was equally effective or slightly better than the conventional AR for the relief of hot flashes, night sweats, and sleep disturbances in perimenopausal and postmenopausal women. Recommendations for future research include confirmatory studies and trials with larger samples. PMID- 24235849 TI - MUCI positive cutaneous metastasis with transepidermal elimination from a breast carcinoma. AB - Breast cancer is the most common cause of cutaneous metastases from internal malignancies. Generally, the neoplastic cells are located in the dermis or hypodermis, while a finding of transepidermal elimination on cutaneous metastases is exceptional. In this report we present a patient with perforating cutaneous metastases from breast cancer with mucin 1 expression. Cutaneous, bone, lung, and hepatic lesions were detected two years after the diagnosis of the primary tumor. PMID- 24235850 TI - High-dose, short-interval daptomycin regimen was safe and well tolerated in three patients with chronic renal failure. AB - BACKGROUND: The recommended daptomycin dosage is 4 or 6 mg/kg/day for the treatment of complicated skin and soft tissue infections or for Staphylococcus aureus bacteremia, endocarditis, and osteomyelitis. Every other day administration is usually recommended for patients with mild to moderate renal impairment. Higher doses (>6 mg/kg/day) have been explored as a possible alternative. Daptomycin is considered a safe anti-methicillin-resistant S. aureus (MRSA) drug, although renal dysfunction may be worsened. In this paper we report on three patients with chronic renal failure who received a higher dose of daptomycin daily for successful treatment for MRSA bacteremia, MRSA osteomyelitis, and methicillin-resistant S. epidermidis (MRSE) endocarditis. RESULTS: Previous administration of other drugs, including vancomycin, teicoplanin, and linezolid, had failed. In spite of daily treatment with daptomycin instead of the recommended alternate day regimen, adverse effects, such as elevation of creatinine and creatine phosphokinase, did not occur. CONCLUSION: These experiences suggest that administration of high-dose/short interval daptomycin can be efficient and safe even in the setting of renal dysfunction, and should be considered for the treatment of severe MRSA/MRSE infections in these patients. PMID- 24235851 TI - Syringeless power injector versus dual-syringe power injector: economic evaluation of user performance, the impact on contrast enhanced computed tomography (CECT) workflow exams, and hospital costs. AB - OBJECTIVE: The utilization of diagnostic imaging has substantially increased over the past decade in Europe and North America and continues to grow worldwide. The purpose of this study was to develop an economic evaluation of a syringeless power injector (PI) versus a dual-syringe PI for contrast enhanced computed tomography (CECT) in a hospital setting. MATERIALS AND METHODS: Patients (n=2379) were enrolled at the Legnano Hospital between November 2012 and January 2013. They had been referred to the hospital for a CECT analysis and were randomized into two groups. The first group was examined with a 256-MDCT (MultiDetector Computed Tomography) scanner using a syringeless power injector, while the other group was examined with a 64-MDCT scanner using a dual-syringe. Data on the operators' time required in the patient analysis steps as well as on the quantity of consumable materials used were collected. The radiologic technologists' satisfaction with the use of the PIs was rated on a 10-point scale. A budget impact analysis and sensitivity analysis were performed under the base-case scenario. RESULTS: A total of 1,040 patients were examined using the syringeless system, and 1,339 with the dual-syringe system; the CECT examination quality was comparable for both PI systems. Equipment preparation time and releasing time per examination for syringeless PIs versus dual-syringe PIs were 100+/-30 versus 180+/-30 seconds and 90+/-30 and 140+/-20 seconds, respectively. On average, 10+/ 3 mL of contrast media (CM) wastage per examination was observed with the dual syringe PI and 0+/-1 mL with the syringeless PI. Technologists had higher satisfaction with the syringeless PI than with the dual-syringe system (8.8 versus 8.0). The syringeless PI allows a saving of about ?6.18 per patient, both due to the lower cost of the devices and to the better performance of the syringeless system. The univariate sensitivity analysis carried out on the base case results within the standard deviation range confirmed the saving generated by using the syringeless device, with saving values between ?5.40 and ?6.20 per patient. CONCLUSION: The syringeless PI was found to be more user-friendly and efficient, minimizing contrast wastage and providing similar contrast enhancement quality compared to the dual-syringe injector, with comparable CECT examination quality. PMID- 24235852 TI - Clinical indicators for severe prognosis of scrub typhus. AB - BACKGROUND: The study explored clinical risk characteristics that may be used to forecast scrub typhus severity under routine clinical practices. METHODS: Retrospective data were collected from patients registered at two university affiliated tertiary care hospitals in the north of Thailand, from 2004 to 2010. Key information was retrieved from in-patient records, out patient cards, laboratory reports and registers. Patients were classified into three severity groups: nonsevere, severe (those with at least one organ involvement), and deceased. Prognostic characteristics for scrub typhus severity were analyzed by a multivariable ordinal continuation ratio regression. RESULTS: A total of 526 patients were classified into nonsevere (n = 357), severe (n = 100), and deceased (n = 69). The significant multivariable prognostic characteristics for scrub typhus severity were increased body temperature (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.45-0.74, P < 0.001), increased pulse rate (OR = 1.03, 95% CI = 1.01-1.05, P < 0.001), presence of crepitation (OR = 3.25, 95% CI = 1.52-6.96, P = 0.001), increased percentage of lymphocytes (OR = 0.97, 95% CI = 0.95-0.98, P = 0.001), increased aspartate aminotransferase (every 10 IU/L) (OR = 1.04, 95% CI = 1.02-1.06, P < 0.001), increased serum albumin (OR = 0.47, 95% CI = 0.27-0.80, P = 0.001), increased serum creatinine (OR = 1.83, 95% CI = 1.50 2.24, P < 0.001), and increased levels of positive urine albumin (OR = 1.43, 95% CI = 1.17-1.75, P < 0.001). CONCLUSION: Patients suspicious of scrub typhus with low body temperature, rapid pulse rate, presence of crepitation, low percentage of lymphocyte, low serum albumin, elevated aspartate aminotransferase, elevated serum creatinine, and positive urine albumin should be monitored closely for severity progression. PMID- 24235854 TI - Interprofessional education: the inclusion of dental hygiene in health care within the United States - a call to action. AB - There is a lack of access to oral health care in the United States for rural, underserved, uninsured, and low-income populations. There are widely recognized problems with the US health care system, including rapidly increasing costs and access to oral health. During the last decade, there has been a huge influx and push toward interprofessional education programs; however, these programs conveniently leave out dental hygiene. Interprofessional education can bring forth the collaboration, communication, and teamwork necessary to provide a comprehensive health care plan to treat oral health care needs in patients. As the advanced practice for dental hygiene emerges, it is imperative that the educational qualifications of dental hygienists are sufficient to enable them to safely provide the scope of services and care encompassed in these new expanded roles and to effectively participate as an interprofessional team member. PMID- 24235853 TI - Contribution of blood platelets to vascular pathology in Alzheimer's disease. AB - Cerebral amyloid angiopathy (CAA) is a critical factor in the pathogenesis of Alzheimer's disease (AD). In the clinical setting, nearly 98% AD patients have CAA, and 75% of these patients are rated as severe CAA. It is characterized by the deposition of the beta-amyloid peptide (mainly Abeta40) in the walls of cerebral vessels, which induces the degeneration of vessel wall components, reduces cerebral blood flow, and aggravates cognitive decline. Platelets are anuclear cell fragments from bone marrow megakaryocytes and their function in hemostasis and thrombosis has long been recognized. Recently, increasing evidence suggests that platelet activation can also mediate the onset and development of CAA. First, platelet activation and adhesion to a vessel wall is the initial step of vascular injury. Activated platelets contribute to more than 90% circulating Abeta (mainly Abeta1-40), which in turn activates platelets and results in the vicious cycle of Abeta overproduction in damaged vessel. Second, the uncontrolled activation of platelets leads to a chronic inflammatory reaction by secretion of chemokines (eg, platelet factor 4 [PF4], regulated upon activation normal T-cell expressed and presumably secreted [RANTES], and macrophage inflammatory protein [MIP-1alpha]), interleukins (IL-1beta, IL-7, and IL-8), prostaglandins, and CD40 ligand (CD40L). The interaction of these biological response modulators with platelets, endothelial cells, and leukocytes establishes a localized inflammatory response that contributes to CAA formation. Finally, activated platelets are the upholder of fibrin clots, which are structurally abnormal and resistant to degradation in the presence of Abeta42. Thus, opinion has emerged that targeting blood platelets may provide a new avenue for anti-AD therapy. PMID- 24235855 TI - Improvement of workflow and processes to ease and enrich meaningful use of health information technology. AB - The introduction of health information technology (HIT) can have unexpected and unintended patient safety and/or quality consequences. This highly desirable but complex intervention requires workflow changes in order to be effective. Workflow is often cited by providers as the number one 'pain point'. Its redesign needs to be tailored to the organizational context, current workflow, HIT system being introduced, and the resources available. Primary care practices lack the required expertise and need external assistance. Unfortunately, the current methods of using esoteric charts or software are alien to health care workers and are, therefore, perceived to be barriers. Most importantly and ironically, these do not readily educate or enable staff to inculcate a common vision, ownership, and empowerment among all stakeholders. These attributes are necessary for creating highly reliable organizations. We present a tool that addresses US Accreditation Council for Graduate Medical (ACGME) competency requirements. Of the six competencies called for by the ACGME, the two that this tool particularly addresses are 'system-based practice' and 'practice-based learning and continuing improvement'. This toolkit is founded on a systems engineering approach. It includes a motivational and orientation presentation, 128 magnetic pictorial and write-erase icons of 40 designs, dry-erase magnetic board, and five visual aids for reducing cognitive and emotive biases in staff. Pilot tests were carried out in practices in Western New York and Colorado, USA. In addition, the toolkit was presented at the 2011 North American Primary Care Research Group (NAPCRG) meeting and an Agency for Health Research and Quality (AHRQ) meeting in 2013 to solicit responses from attendees. It was also presented to the officers of the Office of the National Coordinator (ONC) for HIT. All qualitative feedback was extremely positive and enthusiastic. The respondents recommended that the toolkit be disseminated widely to improve staff education and training, leading to practice improvements. PMID- 24235856 TI - Factors contributing to lack of interest in research among medical students. AB - BACKGROUND: Research experiences early in the medical student's education are an important factor for attracting a greater number of doctors to careers with a research component. OBJECTIVE: To determine the factors contributing to a lack of enthusiasm about research activities among medical students, and to suggest ways to help students develop an interest in research. DESIGN: A medical institution based, case-control study was conducted. A case was defined as any fourth year medical student who believed that undertaking research was not interesting; controls were matched for age and sex. A pretested, structured, and self administered questionnaire was used; the data were analyzed using statistical methods. RESULTS: In all, 122 students (54% male, 46% female) were recruited to the study. Factors found to be significant were lack of Internet facilities (odds ratio 0.218) and considering research useless (odds ratio 4.570). CONCLUSION: Measures should be taken at undergraduate level to involve students in research activities. Ensuring easy access to Internet facilities could be one positive step. Further research should be done to explore the reasons why some medical students consider research useless. PMID- 24235857 TI - Inhibitory effect of Korean Red Ginseng on melanocyte proliferation and its possible implication in GM-CSF mediated signaling. AB - Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation (30 mJ/cm(2)), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation. PMID- 24235858 TI - Effects of Korean Red Ginseng extract on tissue plasminogen activator and plasminogen activator inhibitor-1 expression in cultured rat primary astrocytes. AB - Korean Red Ginseng (KRG) is an oriental herbal preparation obtained from Panax ginseng Meyer (Araliaceae). To expand our understanding of the action of KRG on central nervous system (CNS) function, we examined the effects of KRG on tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) expression in rat primary astrocytes. KRG extract was treated in cultured rat primary astrocytes and neuron in a concentration range of 0.1 to 1.0 mg/mL and the expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and reverse transcription-polymerase chain reaction. KRG extracts increased PAI-1 expression in rat primary astrocytes in a concentration dependent manner (0.1 to 1.0 mg/mL) without affecting the expression of tPA itself. Treatment of 1.0 mg/mL KRG increased PAI-1 protein expression in rat primary astrocytes to 319.3+/-65.9% as compared with control. The increased PAI-1 expression mediated the overall decrease in tPA activity in rat primary astrocytes. Due to the lack of PAI-1 expression in neuron, KRG did not affect tPA activity in neuron. KRG treatment induced a concentration dependent activation of PI3K, p38, ERK1/2, and JNK in rat primary astrocytes and treatment of PI3K or MAPK inhibitors such as LY294002, U0126, SB203580, and SP600125 (10 MUM each), significantly inhibited 1.0 mg/mL KRG-induced expression of PAI- 1 and down-regulation of tPA activity in rat primary astrocytes. Furthermore, compound K but not other ginsenosides such as Rb1 and Rg1 induced PAI-1 expression. KRG-induced up-regulation of PAI-1 in astrocytes may play important role in the regulation of overall tPA activity in brain, which might underlie some of the beneficial effects of KRG on CNS such as neuroprotection in ischemia and brain damaging condition as well as prevention or recovery from addiction. PMID- 24235859 TI - Pharmacokinetics of ginsenoside Rb1 and its metabolite compound K after oral administration of Korean Red Ginseng extract. AB - Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was 8.35+/-3.19 ng/mL, which was significantly higher than that of ginsenoside Rb1 (3.94+/-1.97 ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K. PMID- 24235860 TI - Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography. AB - A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides. PMID- 24235861 TI - Quality and characteristics of ginseng seed oil treated using different extraction methods. AB - Ginseng seed oil was prepared using compressed, solvent, and supercritical fluid extraction methods of ginseng seeds, and the extraction yield, color, phenolic compounds, fatty acid contents, and phytosterol contents of the ginseng seed oil were analyzed. Yields were different depending on the roasting pretreatment and extraction method. Among the extraction methods, the yield of ginseng seed oil from supercritical fluid extraction under the conditions of 500 bar and 65C was the highest, at 17.48%. Color was not different based on the extraction method, but the b-value increased as the roasting time for compression extraction was increased. The b-values of ginseng seed oil following supercritical fluid extraction were 3.54 to 15.6 and those following compression extraction after roasting treatment at 200C for 30 min, were 20.49, which was the highest value. The result of the phenolic compounds composition showed the presence of gentisic acid, vanillic acid, ferulic acid, and cinnamic acid in the ginseng seed oil. No differences were detected in phenolic acid levels in ginseng seed oil extracted by compression extraction or solvent extraction, but vanillic acid tended to decrease as extraction pressure and temperature were increased for seed oil extracted by a supercritical fluid extraction method. The fatty acid composition of ginseng seed oil was not different based on the extraction method, and unsaturated fatty acids were >90% of all fatty acids, among which, oleic acid was the highest at 80%. Phytosterol analysis showed that beta-sitosterol and stigmasterol were detected. The phytosterol content of ginseng seed oil following supercritical fluid extraction was 100.4 to 135.5 mg/100 g, and the phytosterol content following compression extraction and solvent extraction was 71.8 to 80.9 mg/100 g. PMID- 24235862 TI - A new validated analytical method for the quality control of red ginseng products. AB - The main active components of Panax ginseng are ginsenosides. Ginsenoside Rb1 and Rg1 are accepted as marker substances for quality control worldwide. The analytical methods currently used to detect these two compounds unfairly penalize steamed and dried (red) P. ginseng preparations, because it has a lower content of those ginsenosides than white ginseng. To manufacture red ginseng products from fresh ginseng, the ginseng roots are exposed to high temperatures for many hours. This heating process converts the naturally occurring ginsenoside Rb1 and Rg1 into artifact ginsenosides such as ginsenoside Rg3, Rg5, Rh1, and Rh2, among others. This study highlights the absurdity of the current analytical practice by investigating the time-dependent changes in the crude saponin and the major natural and artifact ginsenosides contents during simmering. The results lead us to recommend (20S)- and (20R)-ginsenoside Rg3 as new reference materials to complement the current P. ginseng preparation reference materials ginsenoside Rb1 and Rg1. An attempt has also been made to establish validated qualitative and quantitative analytical procedures for these four compounds that meet International Conference of Harmonization (ICH) guidelines for specificity, linearity, range, accuracy, precision, detection limit, quantitation limit, robustness and system suitability. Based on these results, we suggest a validated analytical procedure which conforms to ICH guidelines and equally values the contents of ginsenosides in white and red ginseng preparations. PMID- 24235863 TI - Luminescence properties and compositions of contaminating inorganic minerals separated from gamma-irradiated fresh and white ginsengs from different areas. AB - Gamma-irradiation (0-7 kGy) of ginseng is permitted in Korea for the purpose of microbial decontamination; with strict labeling, traceability and monitoring requirements. An identification study was conducted to determine the photostimulated-luminescence (PSL) and thermoluminescence (TL) properties of gamma-irradiated fresh and white ginsengs cultivated in different areas. Dosedependent PSL-based screening was possible for white ginseng samples; however, inappropriate results from non-irradiated fresh ginseng samples were obtained, showing intermediate (700 to 5,000) or positive (T2 >5,000, irradiated) PSL counts due to the abundance of minerals on the surfaces of the samples. TL analysis of separated minerals from all non-irradiated samples gave TL glow curves of low intensity with a maximum peak after 300C. However, well-defined irradiation-specific (high intensity with a maximum peak at about 200C) glow curves were observed for all the irradiated samples, regardless of their type and origins. TL ratios (first glow curve /second glow curve) were also determined to confirm the irradiated (>0.1) and non-irradiated (<0.1) results. SEM-EDX (scanning electron microscope-energy dispersive X-ray) and XRD (X-ray diffraction) spectroscopic analyses showed that feldspar and quartz minerals were the main source for the typical radiation-specific luminescence properties. PMID- 24235864 TI - Geographic information system-based identification of suitable cultivation sites for wood-cultivated ginseng. AB - Wood-cultivated ginseng, including roots in its dried form, is produced in forest land without using artificial facilities such as light barriers. To identify suitable sites for the propagation of wood-cultivated ginseng, factor combination technique (FCT) and linear combination technique (LCT) were used with geographic information system and the results were superimposed onto an actual wood cultivated ginseng plantation. The LCT more extensively searched for suitable sites of cultivation than that by the FCT; further, the LCT probed wide areas considering the predominance of precipitous mountains in Korea. In addition, the LCT showed the much higher degree of overlap with the actual cultivation sites; therefore, the LCT more comprehensively reflects the cultivator's intention for site selection. On the other hand, the inclusion of additional factors for the selection of suitable cultivation sites and experts' opinions may enhance the effectiveness and accuracy of the LCT for site application. PMID- 24235865 TI - Role of epigenetic reprogramming of host genes in bacterial pathogenesis. AB - The genomes are regularly targeted by epigenetic regulatory mechanisms (DNA methylation, histone modifications, binding of regulatory proteins) in infected cells. In addition, proteins encoded by microbial genomes may disturb the action of a set of cellular promoters by interacting with the same epi-regulatory machinery. The outcome of this may result in epigenetic dysregulation and subsequent cellular dysfunctions that may manifest in or contribute to the development of pathological changes. How epigenetic methylation decorations on DNA and histones are started and established remains largely unknown. The inherited nature of these processes in regulation of genes suggests that they could play key roles in chronic diseases associated with microbial persistence; they might also explain so-called hit-and-run phenomena in infectious disease pathogenesis. Microbes infecting mammals may cause diseases by causing hyper methylation of key cellular promoters at CpG di-nucleotides and may induce pathological changes by epigenetic reprogramming of host cells they are interacting with elucidation of the epigenetic consequences of microbe-host interactions may have important therapeutic implications because epigenetic processes can be reverted and elimination of microbes inducing patho-epigenetic changes may prevent disease development. PMID- 24235866 TI - Molecular identification of isolated fungi from stored apples in Riyadh, Saudi Arabia. AB - Fungi causes most plant disease. When fruits are stored at suboptimal conditions, fungi grows, and some produce mycotoxin which can be dangerous for human consumption. Studies have shown that the Penicillium and Monilinia species commonly cause spoilage of fruits, especially apples. Several other genera and species were reported to grow to spoil fruits. This study was conducted to isolate and identify fruit spoilage by fungi on apples collected in Riyadh, Saudi Arabia and conduct a molecular identification of the fungal isolates. Thus, we collected 30 samples of red delicious and Granny Smith apples with obvious spoilage from different supermarkets between February and March of 2012 in Riyadh, Saudi Arabia. Each apple was placed in a sterile plastic bag in room temperature (25-30 degrees C) for six days or until fungal growth was evident all over the sample. Growth of fungal colonies on PDA was counted and sent for molecular confirmation by PCR. Six fruit spoilage fungi were isolated, including Penicillium chrysogenum, Penicillium adametzii, Penicillium chrysogenum, Penicillium steckii, Penicillium chrysogenum, and Aspergillus oryzae. P. chrysogenum was the most frequent isolate which was seen in 14 of a total of 34 isolates (41.2%), followed by P. adametzii and A. oryzae with seven isolates each (20.6%) and the least was P. steckii with six isolates (17.6%). Penicillium species comprised 27 of the total 34 (79.4%) isolates. Sequence analysis of the ITS regions of the nuclear encoded rDNA showed significant alignments for P. chrysogenum, P. adametzii and A. oryzae. Most of these fungal isolates are useful and are rarely pathogenic; however they can still produce severe illness in immune-compromised individuals, and sometimes otherwise healthy people may also become infected. It is therefore necessary to evaluate the possible production of mycotoxins by these fungi to determine a potential danger and to establish its epidemiology in order to develop adequate methods of control. PMID- 24235867 TI - Free radical scavenging activity from different extracts of leaves of Bauhinia vahlii Wight & Arn. AB - The objectives of this study were to determine phenolic content and antioxidant activities of chloroform, acetone, methanol and hot water extracts of Bauhinia vahlii leaves. The hot water extract afforded the highest yield (6.3%) while the lowest yield was obtained from the chloroform extract (2.1%). The methanol extract contains higher levels of total phenolics (48.7 +/- 0.7 g GAE/100 g extract), tannins (21.7 +/- 0.7 g GAE/100 g extract) and flavonoids (10.3 +/- 0.2 RE/100 g extract). The extracts were subjected to assess their antioxidant potential using various in vitro systems such as DPPH(*), ABTS(*+), FRAP, OH(*), beta-carotene linoleic acid bleaching system, phosphomolybdenum reduction and Fe(2+) chelation. It is concluded that the methanolic extract of B. vahlii leaves have strong antioxidant potential. Further study is necessary for isolation and characterization of the active antioxidants, which may serve as a potential source of natural antioxidants. PMID- 24235868 TI - Labeling of nucleosides with fluorescamine and detection by spectrofluorometer for End Stage Renal Disease. AB - Nucleosides are characterized as biomarkers in AIDS, Alzheimer, tumor, breast cancer and various malignant diseases. In the present work a direct method for the detection of nucleosides (adenosine, cytidine, uridine and guanosine) from urine samples has been developed. Nucleosides represent the extent of damage in genetic material, analysis of nucleosides by ultrasonic assisted microextraction effectively eliminates the interfering constituent of urine. This has made it a highly selective and sensitive method to analyze the nucleosides with a lower limit of detection 0.220 MUmol/L and Limit of quantitation 0.660 MUmol/L. The method has been validated with good linearity and correlation of coefficients of the calibration curves was higher than 0.997. The coefficients were in the range of 0.11-16.92% (inter-day) and 0.38-16.43% (intra-day), respectively. PMID- 24235869 TI - Yield and size of oyster mushroom grown on rice/wheat straw basal substrate supplemented with cotton seed hull. AB - Oyster mushroom (Pleurotus ostreatus) was cultivated on rice straw basal substrate, wheat straw basal substrate, cotton seed hull basal substrate, and wheat straw or rice straw supplemented with different proportions (15%, 30%, and 45% in rice straw substrate, 20%, 30%, and 40% in wheat straw substrate) of cotton seed hull to find a cost effective substrate. The effect of autoclaved sterilized and non-sterilized substrate on growth and yield of oyster mushroom was also examined. Results indicated that for both sterilized substrate and non sterilized substrate, oyster mushroom on rice straw and wheat basal substrate have faster mycelial growth rate, comparatively poor surface mycelial density, shorter total colonization period and days from bag opening to primordia formation, lower yield and biological efficiency, lower mushroom weight, longer stipe length and smaller cap diameter than that on cotton seed hull basal substrate. The addition of cotton seed hull to rice straw and wheat straw substrate slowed spawn running, primordial development and fruit body formation. However, increasing the amount of cotton seed hull can increase the uniformity and white of mycelium, yield and biological efficiency, and increase mushroom weight, enlarge cap diameter and shorten stipe length. Compared to the sterilized substrate, the non-sterilized substrate had comparatively higher mycelial growth rate, shorter total colonization period and days from bag opening to primordia formation. However, the non-sterilized substrate did not gave significantly higher mushroom yield and biological efficiency than the sterilized substrate, but some undesirable characteristics, i.e. smaller mushroom cap diameter and relatively long stipe length. PMID- 24235870 TI - Improved growth, productivity and quality of tomato (Solanum lycopersicum L.) plants through application of shikimic acid. AB - A field experiment was conducted to investigate the effect of seed presoaking of shikimic acid (30, 60 and 120 ppm) on growth parameters, fruit productivity and quality, transpiration rate, photosynthetic pigments and some mineral nutrition contents of tomato plants. Shikimic acid at all concentrations significantly increased fresh and dry weights, fruit number, average fresh and dry fruit yield, vitamin C, lycopene, carotenoid contents, total acidity and fruit total soluble sugars of tomato plants when compared to control plants. Seed pretreatment with shikimic acid at various doses induces a significant increase in total leaf conductivity, transpiration rate and photosynthetic pigments (Chl. a, chl. b and carotenoids) of tomato plants. Furthermore, shikimic acid at various doses applied significantly increased the concentration of nitrogen, phosphorus and potassium in tomato leaves as compared to control non-treated tomato plants. Among all doses of shikimic acid treatment, it was found that 60 ppm treatment caused a marked increase in growth, fruit productivity and quality and most studied parameters of tomato plants when compared to other treatments. On the other hand, no significant differences were observed in total photosynthetic pigments, concentrations of nitrogen and potassium in leaves of tomato plants treated with 30 ppm of shikimic acid and control plants. According to these results, it could be suggested that shikimic acid used for seed soaking could be used for increasing growth, fruit productivity and quality of tomato plants growing under field conditions. PMID- 24235871 TI - Enhanced decolorization of Solar brilliant red 80 textile dye by an indigenous white rot fungus Schizophyllum commune IBL-06. AB - An indigenously isolated white rot fungus, Schizophyllum commune IBL-06 was used to decolorize Solar brilliant red 80 direct dye in Kirk's basal salts medium. In initial screening study, the maximum decolorization (84.8%) of Solar brilliant red 80 was achieved in 7 days shaking incubation period at pH 4.5 and 30 degrees C. Different physical and nutritional factors including pH, temperature and fungal inoculum density were statistically optimized through Completely Randomized Design (CRD), to enhance the efficiency of S. commune IBL-06 for maximum decolorization of Solar brilliant red 80 dye. The effects of inexpensive carbon and nitrogen sources were also investigated. Percent dye decolorization was determined by a reduction in optical density at the wavelength of maximum absorbance (lambda max, 590 nm). Under optimum conditions, the S. commune IBL-06 completely decolorized (100%) the Solar brilliant red 80 dye using maltose and ammonium sulfate as inexpensive carbon and nitrogen sources, respectively in 3 days. S. commune IBL-06 produced the three major ligninolytic enzymes lignin peroxidase (LiP), manganase peroxidase (MnP) and lacaase (Lac) during the decolorization of Solar brilliant red 80. LiP was the major enzyme (944 U/mL) secreted by S. commune IBL-06 along with comparatively lower activities of MnP and Laccase. PMID- 24235872 TI - Selective inhibition of toxic cyanobacteria by beta-carboline-containing bacterium Bacillus flexus isolated from Saudi freshwaters. AB - A bacterial strain SSZ01 isolated from a eutrophic lake in Saudi Arabia dominated by cyanobacterial blooms, showed an antialgal activity against cyanobacteria species. Based on the analysis of the 16S rDNA gene sequence, the isolated strain (SSZ01) most likely belonged to the genus Bacillus with a 99% similarity to Bacillus flexus strain EMGA5. The thin layer chromatography (TLC) analysis of the ethyl acetate extract of this bacterium revealed that this strain can produce harmine and norharmane compared to different beta-carboline analog standards. Harmine and norharmane were also detected in considerable amounts in bacterial growth medium, indicating a potential excretion of these compounds into the aquatic environment. The crude extract of Bacillus flexus as well as pure materials of harmine and norharmane inhibited the growth of tested species of cyanobacteria. However, the bacterial crude extract has a higher toxicity against tested species of cyanobacteria than harmine and norharmane. In addition, harmine was more toxic to cyanobacteria than norharmane. On the other hand, neither pure compounds of harmine and norharmane nor crude bacterial extract showed any antialgal activity against tested species of green algae. The results of the present study suggest that B. flexus SSZ01 or its crude extract containing harmine and norharmane could be a candidate for the selective control of cyanobacterial blooms without affecting other algal species. PMID- 24235873 TI - Analgesic and anti-inflammatory studies of cyclopeptide alkaloid fraction of leaves of Ziziyphus nummularia. AB - Ziziyphus nummularia (family: Rhamnaceae) is a thorny small bush, grows in abundance in the grazing lands of the arid areas of Rajasthan, India. It is an important ethnomedicinal plant of the Thar Desert; local inhabitants use every part of the plant as medicine. Kernels are prescribed in pregnancy as soporific, antiemetic and for relieving abdominal pain. The insect gall is powered and given orally with water to cure bone fracture. Crushed root is applied on the paining shoulder of the bullock. The decoction of leaves is used for the treatment of cough and cold; leaves are also regarded as diaphoretic and prescribed in typhoid. Paste of leaves is used for healing of cuts, boils and cutaneous disease. It is widely used in pain and inflammatory conditions. Z. nummularia contains a unique group of alkaloids known as cyclopeptide alkaloids, in continuation of our work carried out on the leaves of Z. nummularia , present study was initiated to explore antiinflammatory and analgesic potential of cyclopeptide alkaloids isolated from the leaves of Z. nummularia (IFZN). Anti inflammatory activity was tested against rat paw oedema, mouse peritonitis and cotton pellet granuloma. For screening of analgesic activity, acetic acid induced writhing, tail flick and hot plate test were performed. IFZN 30 mg/kg shows the anti-oedematogenic effect against paw oedema induced by carrageenan, dextran, serotonin and histamine; IFZN 20 and 30 mg/kg were found to have highly significant anti-nociceptive effects. Result of pharmacological studies indicated that IFZN is a potent and efficacious analgesic agent. The analgesic activity of IFZN is mediated by the peripheral as well as central pathways. PMID- 24235874 TI - Characterization and kinetic properties of the purified Trematosphaeria mangrovei laccase enzyme. AB - The properties of Trematosphaeria mangrovei laccase enzyme purified on Sephadex G 100 column were investigated. SDS-PAGE of the purified laccase enzyme showed a single band at 48 kDa. The pure laccase reached its maximal activity at temperature 65 degrees C, pH 4.0 with K m equal 1.4 mM and V max equal 184.84 U/mg protein. The substrate specificity of the purified laccase was greatly influenced by the nature and position of the substituted groups in the phenolic ring. The pure laccase was tested with some metal ions and inhibitors, FeSO4 completely inhibited laccase enzyme and also highly affected by (NaN3) at a concentration of 1 mM. Amino acid composition of the pure enzyme was also determined. Carbohydrate content of purified laccase enzyme was 23% of the enzyme sample. The UV absorption spectra of the purified laccase enzyme showed a single peak at 260-280 nm. PMID- 24235875 TI - Heavy metal analysis in commercial Spirulina products for human consumption. AB - For consumption of health foods of Spirulina, by the general public, health food stores are increasingly offering more exotic products. Though Spirulina consumption is growing worldwide, relatively few studies have reported on the quantities of heavy metals/minerals they contain and/or their potential effects on the population's health. This study reveals the concentrations of six typical heavy metals/minerals (Ni, Zn, Hg, Pt, Mg, and Mn) in 25 Spirulina products commercialized worldwide for direct human consumption. Samples were ground, digested and quantified by Coupled Plasma Mass Spectroscopy (ICP-MS). The concentrations (mg/kg d.w.) were range from 0.001 to 0.012 (Pt) followed by 0.002 0.028 (Hg), 0.002-0.042 (Mg), 0.005-2.248 (Mn), 0.211-4.672 (Ni) and 0.533-6.225 (Zn). The inorganic elements of the present study were significantly lower than the recommended daily intake (RDI) level of heavy metal elements (mg/daily) Ni (0.4), Zn (13), Hg (0.01), Pt (0.002), Mg (400) and Mn (4). Based on this study the concentration of inorganic elements was not found to exceed the present regulation levels, and they can be considered as safe food. PMID- 24235876 TI - The Role of Attention in the Binding of Surface Features to Locations. AB - Previous studies have proposed that attention is not necessary for detecting simple features but is necessary for binding them to spatial locations. The present study tested this hypothesis, using the N2pc component of the event related potential waveform as a measure of the allocation of attention. A simple feature detection condition, in which observers reported whether a target color was present or not, was compared with feature-location binding conditions, in which observers reported the location of the target color. A larger N2pc component was observed in the binding conditions than in the detection condition, indicating that additional attentional resources are needed to bind a feature to a location than to detect the feature independently of its location. This finding supports theories of attention in which attention plays a special role in binding features. PMID- 24235877 TI - Fathering and Adolescent Adjustment: Variations by Family Structure and Ethnic Background. AB - The current study investigated how fathering behaviors (acceptance, rejection, monitoring, consistent discipline, and involvement) are related to preadolescent adjustment in Mexican American and European American stepfamilies and intact families. Cross-sectional data from 393 7th graders, their schoolteachers, and parents were used to examine links between different dimensions of fathering and adolescent outcomes. Following an ecological multivariate model, family SES, marital satisfaction, and mothers' parenting were included as controls. In all contexts, fathering had significant effects on adolescent adjustment. Both mothers' parenting and adolescent gender moderated the associations, and we uncovered some provocative nonlinear relations between fathering and adolescent outcomes. The importance of ethnicity and family structure in studies of fathering are highlighted. PMID- 24235878 TI - Association of blood pressure and hypertension with alcohol consumption in HIV infected white and nonwhite patients. AB - INTRODUCTION: Although alcohol abuse is associated with hypertension in whites and nonwhites, it has been scarcely investigated in HIV-infected patients. OBJECTIVE: To investigate whether the association of alcohol abuse with hypertension is influenced by skin color in HIV-infected individuals. METHODS: Cross-sectional study in HIV-infected individuals aged 18 years or older. Demographic characteristics, lifestyle, and HIV infection were investigated. Alcohol abuse was defined as >= 15 (women) and >= 30 g/alcohol/day (men), and binge drinking by the intake of >= 5 drinks on a single occasion. Hypertension was defined by blood pressure >= 140/90 mmHg or use of blood pressure-lowering agents. RESULTS: We studied 1,240 individuals, with 39.1 +/- 10 years, 51% males and 57% whites. Age and body mass index were associated with blood pressure, and there was an independent association of alcohol abuse with hypertension in whites (RR = 1.9, 95% CI 1.1-3.3) and nonwhites (RR = 2.4, 95% CI 1.4 to 4.0). Among nonwhite individuals who were alcohol abusers, systolic (9.3 +/- 3.2; P = 0.001) and diastolic blood pressures (6.4 +/- 2.1; P = 0.008) were higher than in nonabusers. CONCLUSION: Alcohol abuse is a risk factor for hypertension in white and nonwhite HIV-infected individuals. The association of ethanol consumption with blood pressure is not explained by AIDS-related conditions. PMID- 24235879 TI - Freestyle-like V-Y flaps of the eyebrow: a new outlook and indication of an historical technique. AB - The eyebrow region is of utmost importance for facial movement, symmetry, and the overall cosmetic appearance of the face. Trauma or tumor resection often leave scars that may dislocate the eyebrow producing an alteration both in static symmetry of the face and in the dynamic expressivity. The authors present a technique for eyebrow's defects repair using the remaining eyebrow advancement by means of a "freestyle-like" V-Y flap. In the past two years a total of eight consecutive patients underwent excision of skin lesions in the superciliary region and immediate reconstruction with this technique. On histology, six patients were affected from basal cell carcinomas, one from squamous cell carcinoma, and one from congenital intradermal melanocytic nevus. The pedicle of the flap included perforators from the supratrochlear, supraorbital, or superficial temporalis artery. Advancement of the entire aesthetic subunit that includes the eyebrow using a V-Y perforator flap was performed successfully in all cases achieving full, tension-free closure of defects up to 3.0 cm. "Freestyle-like" V-Y flaps should be considered as a first-line choice for partial defects of the eyebrow. The greater mobility compared to random subcutaneous flaps allows to reconstruct large defects providing an excellent cosmetic result. PMID- 24235880 TI - Prostate cancer: all aspects. PMID- 24235881 TI - Topographic dependence of cropland transformation in China during the first decade of the 21st century. AB - Terrain plays a critical role in the selection of cropland. As a physical and geographical element of the landscape, terrain is an important limiting factor in land use change and has a strong influence on human activities. The objectives of this study are to investigate the topographic characteristics of cropland-related transformations in China during the first decade of the 21st century and to explore the implications of land use change as it relates to securing a national food supply. A 2010 satellite-based land use dataset and the DEM data were used to conduct spatial statistical analysis using altitude, slope, and fragmentation data. The results showed the following. (1) As the urbanization and industrialization of China occur, and China attempts to replace this occupied cropland with newly reclaimed cropland, the topography of the most recently reclaimed cropland has been more poorly suited to farming than the topography of the occupied cropland it replaces in most provinces. (2) The area of occupied cropland was much larger than of those reclaimed; the qualities of occupied and reclaimed cropland were significantly different. (3) Land reclamation mainly occurred in northern China, instead of in southern China, which has a higher level of economic development. Our findings imply that the potential area available for cropland production may be limited. PMID- 24235883 TI - Morphological, physiological, and structural responses of two species of artemisia to NaCl stress. AB - Effects of salt stress on Artemisia scoparia and A. vulgaris "Variegate" were examined. A. scoparia leaves became withered under NaCl treatment, whereas A. vulgaris "Variegate" leaves were not remarkably affected. Chlorophyll content decreased in both species, with a higher reduction in A. scoparia. Contents of proline, MDA, soluble carbohydrate, and Na(+) increased in both species under salt stress, but A. vulgaris "Variegate" had higher level of proline and soluble carbohydrate and lower level of MDA and Na(+). The ratios of K(+)/Na(+), Ca(2+)/Na(+), and Mg(2+)/Na(+) in A. vulgaris "Variegate" under NaCl stress were higher. Moreover, A. vulgaris "Variegate" had higher transport selectivity of K(+)/Na(+) from root to stem, stem to middle mature leaves, and upper newly developed leaves than A. scoparia under NaCl stress. A. vulgaris "Variegate" chloroplast maintained its morphological integrity under NaCl stress, whereas A. scoparia chloroplast lost integrity. The results indicated that A. scoparia is more sensitive to salt stress than A. vulgaris "Variegate." Salt tolerance is mainly related to the ability of regulating osmotic pressure through the accumulation of soluble carbohydrates and proline, and the gradient distribution of K(+) between roots and leaves was also contributed to osmotic pressure adjustment and improvement of plant salt tolerance. PMID- 24235882 TI - Thiamine deficiency induced neurochemical, neuroanatomical, and neuropsychological alterations: a reappraisal. AB - Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID- 24235884 TI - NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features. AB - OBJECTIVE: We retrospectively analyzed all primary aldosteronism (PA) patients undergoing NP-59 SPECT/CT imaging with regard to their clinicolaboratory and imaging features, investigation, and outcomes. MATERIAL AND METHODS: 11 PA patients who presented to our hospital for NP-59 SPECT/CT imaging between April 2007 and March 2012 and managed here were analyzed. RESULTS: Among 11 PA patients, eight (73%) had stage 1 hypertension, three (27%) stage 2 hypertension, four (36%) normal plasma aldosterone concentration, nine (82%) nonsuppressed plasma renin activity (PRA), six (55%) normal aldosterone-renin-ratio (ARR), eight (73%) serum potassium ?3 mEq/L, seven (64%) subclinical presentation, seven (64%) negative confirmatory testing, and four (36%) inconclusive results on CT scan and seven (64%) on planar NP-59 scan. All 11 (100%) patients had positive results on NP-59 SPECT/CT scan. Two (18%) met typical triad and nine (82%) atypical triad. Among nine atypical PA patients, three (33%) had clinical presentation, six (67%) subclinical presentation, six (67%) negative confirmatory testing, and four (44%) inconclusive results on CT scan and six (67%) on planar NP-59 scan. All patients had improved outcomes. Significant differences between typical and atypical PA existed in PRA and ARR. CONCLUSIONS: NP-59 SPECT/CT may provide diagnostic potential in stage 1 hypertensive and atypical PA. PMID- 24235885 TI - Coupled electrokinetics-adsorption technique for simultaneous removal of heavy metals and organics from saline-sodic soil. AB - In situ remediation technologies for contaminated soils are faced with significant technical challenges when the contaminated soil has low permeability. Popular traditional technologies are rendered ineffective due to the difficulty encountered in accessing the contaminants as well as when employed in settings where the soil contains mixed contaminants such as petroleum hydrocarbons, heavy metals, and polar organics. In this study, an integrated in situ remediation technique that couples electrokinetics with adsorption, using locally produced granular activated carbon from date palm pits in the treatment zones that are installed directly to bracket the contaminated soils at bench-scale, is investigated. Natural saline-sodic soil, spiked with contaminant mixture (kerosene, phenol, Cr, Cd, Cu, Zn, Pb, and Hg), was used in this study to investigate the efficiency of contaminant removal. For the 21-day period of continuous electrokinetics-adsorption experimental run, efficiency for the removal of Zn, Pb, Cu, Cd, Cr, Hg, phenol, and kerosene was found to reach 26.8, 55.8, 41.0, 34.4, 75.9, 92.49, 100.0, and 49.8%, respectively. The results obtained suggest that integrating adsorption into electrokinetic technology is a promising solution for removal of contaminant mixture from saline-sodic soils. PMID- 24235886 TI - The effect of reagents mimicking oxidative stress on fibrinogen function. AB - Fibrinogen is one of the plasma proteins most susceptible to oxidative modification. It has been suggested that modification of fibrinogen may cause thrombotic/bleeding complications associated with many pathophysiological states of organism. We exposed fibrinogen molecules to three different modification reagents-malondialdehyde, sodium hypochlorite, and peroxynitrite-that are presented to various degrees in different stages of oxidative stress. We studied the changes in fibrin network formation and platelet interactions with modified fibrinogens under flow conditions. The fastest modification of fibrinogen was caused by hypochlorite. Fibers from fibrinogen modified with either reagent were thinner in comparison with control fibers. We found that platelet dynamic adhesion was significantly lower on fibrinogen modified with malondialdehyde and significantly higher on fibrinogen modified either with hypochlorite or peroxynitrite reflecting different prothrombotic/antithrombotic properties of oxidatively modified fibrinogens. It seems that, in the complex reactions ongoing in living organisms at conditions of oxidation stress, hypochlorite modifies proteins (e.g., fibrinogen) faster and more preferentially than malondialdehyde. It suggests that the prothrombotic effects of prior fibrinogen modifications may outweigh the antithrombotic effect of malondialdehyde-modified fibrinogen in real living systems. PMID- 24235887 TI - Optimization and evaluation of desloratadine oral strip: an innovation in paediatric medication. AB - Patients, especially children, are the most difficult to treat in all groups of population mainly because they can not swallow the solid dosage form. Due to this reason they are often prescribed liquid dosage forms. But these formulations have their own disadvantages (lack of dose accuracy during administration, spitting by children, spillage, lack of stability, difficulty in transportation, etc.). Oral strip technology is one such technology to surpass these disadvantages. Desloratadine, a descarboethoxy derivative of loratadine, is a second generation antihistaminic drug approved for usage in allergic rhinitis among paediatric population and is available in markets as suspension. An attempt has been made to design and optimize the oral strip containing desloratadine as an active ingredient. Oral strip was optimized with the help of optimal experimental design using polymer concentration, plasticizer type, and plasticizer concentration as independent variables. Prepared oral strips were evaluated for physicochemical parameter, mechanical strength parameters, disintegration time, dissolution, surface pH, and moisture sorption tendency. Optimized formulation was further evaluated by scanning electron microscopy, moisture content, and histological alteration in oral mucosa. Accelerated stability studies were also carried out for optimized formulations. Results were analysed with the help of various statistical tools at P < 0.05 and P < 0.01. PMID- 24235888 TI - Incomplete augmented Lagrangian preconditioner for steady incompressible Navier Stokes equations. AB - An incomplete augmented Lagrangian preconditioner, for the steady incompressible Navier-Stokes equations discretized by stable finite elements, is proposed. The eigenvalues of the preconditioned matrix are analyzed. Numerical experiments show that the incomplete augmented Lagrangian-based preconditioner proposed is very robust and performs quite well by the Picard linearization or the Newton linearization over a wide range of values of the viscosity on both uniform and stretched grids. PMID- 24235890 TI - Electrochemical properties of PANI as single electrode of electrochemical capacitors in acid electrolytes. AB - The polyaniline (PANI) powder with globular sponge-like morphology was prepared by chemical solution polymerization, and its morphology and chemical structure were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR), respectively. The single electrode of electrochemical capacitor was made using the prepared PANI powder as active material and carbon paper as current collector. Electrochemical properties of PANI as a single electrode in 1 M HCl and 1 M H2SO4 electrolyte solution were tested by galvanostatic charge/discharge (GCD) and cyclic voltammetry (CV) techniques. It has been found that PANI has higher specific capacitance of 302.43 Fg(-1), higher specific energy of 54.44 Wh.kg(-1) at 0.5 Ag(-1), and higher working potential in 1 M HCl than those in 1 M H2SO4. PMID- 24235889 TI - Reliability of a novel CBCT-based 3D classification system for maxillary canine impactions in orthodontics: the KPG index. AB - The aim of this study was to evaluate both intra- and interoperator reliability of a radiological three-dimensional classification system (KPG index) for the assessment of degree of difficulty for orthodontic treatment of maxillary canine impactions. Cone beam computed tomography (CBCT) scans of fifty impacted canines, obtained using three different scanners (NewTom, Kodak, and Planmeca), were classified using the KPG index by three independent orthodontists. Measurements were repeated one month later. Based on these two sessions, several recommendations on KPG Index scoring were elaborated. After a joint calibration session, these recommendations were explained to nine orthodontists and the two measurement sessions were repeated. There was a moderate intrarater agreement in the precalibration measurement sessions. After the calibration session, both intra- and interrater agreement were almost perfect. Indexes assessed with Kodak Dental Imaging 3D module software showed a better reliability in z-axis values, whereas indexes assessed with Planmeca Romexis software showed a better reliability in x- and y-axis values. No differences were found between the CBCT scanners used. Taken together, these findings indicate that the application of the instructions elaborated during this study improved KPG index reliability, which was nevertheless variously influenced by the use of different software for images evaluation. PMID- 24235891 TI - Periodic leg movements are associated with reduced sleep quality in older men: the MrOS Sleep Study. AB - STUDY OBJECTIVES: Periodic limb movements in sleep (PLMS) are common in the elderly. A previous large polysomnographic (PSG) study examining the relationship of PLMS to sleep architecture and arousals from sleep in women found that leg movements were common in elderly women, and PLMS which were associated with EEG arousals had a strong and consistent association with markers of disturbed sleep. Since sleep differs in men and women, we now investigate the association between PLMS and PSG indices of sleep quality in a large community-based sample of older men. DESIGN: Observational study, cross-sectional analyses. SETTING: Six clinical sites participating in the Osteoporotic Fractures in Men (MrOS) Study. PARTICIPANTS: 2,872 older community-dwelling men (mean age 76.4 years) who completed in-home PSG from 2003-2005. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In-home PSG was performed which included bilateral measurement of leg movements. The total number of leg movements per hour of sleep (PLMI) and the number of leg movements causing EEG-documented arousals per hour of sleep (PLMA) were computed. A PLMI >= 5 (70.8%) and PLMA >= 5 (27.4%) were both prevalent. Linear regression models were used to examine the relationship between PLMS as predictors and sleep architecture, arousal index, and sleep efficiency as outcomes. The highest quintiles of PLMI (>= 65.1) and PLMA (>= 6.8) showed the largest association with indices of sleep architecture; PLMA showed a larger magnitude of effect. After multivariate adjustment, participants with a higher PLMA had a small but significantly higher arousal index, lower sleep efficiency, higher percentages of stages 1 and 2 sleep, and lower percentages of stage 3-4 and REM sleep (p < 0.01). An increased PLMI was similarly associated with a higher arousal index, higher percentage of stage 2 sleep, and lower percentage of stage 3-4 (p < 0.0001), but not with an increase in stage 1, REM sleep, or sleep efficiency. Neither PLMI nor PMLA was associated with subjective sleepiness measured by the Epworth Sleepiness Scale. CONCLUSIONS: This study demonstrated that periodic leg movements are very common in older community-dwelling men and regardless of associated arousals, are associated with evidence of lighter and more fragmented sleep. PMID- 24235892 TI - Effects of sleep disorders on the non-motor symptoms of Parkinson disease. AB - STUDY OBJECTIVES: To evaluate the impact of sleep disorders on non-motor symptoms in patients with Parkinson disease (PD). DESIGN: This was a cross-sectional study. Patients with PD were evaluated for obstructive sleep apnea (OSA), restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and REM sleep behavior disorder (RBD). Cognition was assessed with the Montreal Cognitive Assessment and patients completed self-reported questionnaires assessing non motor symptoms including depressive symptoms, fatigue, sleep complaints, daytime sleepiness, and quality of life. SETTING: Sleep laboratory. PARTICIPANTS: 86 patients with PD (mean age = 67.4 +/- 8.8 years; range: 47-89; 29 women). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Having sleep disorders was a predictor of overall non-motor symptoms in PD (R(2) = 0.33, p < 0.001) while controlling for age, PD severity, and dopaminergic therapy. These analyses revealed that RBD (p = 0.006) and RLS (p = 0.014) were significant predictors of increased non-motor symptoms, but OSA was not. More specifically, having a sleep disorder significantly predicted sleep complaints (DeltaR(2) = 0.13, p = 0.006), depressive symptoms (DeltaR(2) = 0.01, p = 0.03), fatigue (DeltaR(2) = 0.12, p = 0.007), poor quality of life (DeltaR(2) = 0.13, p = 0.002), and cognitive decline (DeltaR(2) = 0.09, p = 0.036). Additionally, increasing number of sleep disorders (0, 1, or >= 2 sleep disorders) was a significant contributor to non-motor symptom impairment (R(2) = 0.28, p < 0.001). CONCLUSION: In this study of PD patients, presence of comorbid sleep disorders predicted more non-motor symptoms including increased sleep complaints, more depressive symptoms, lower quality of life, poorer cognition, and more fatigue. RBD and RLS were factors of overall increased non-motor symptoms, but OSA was not. PMID- 24235893 TI - Insomnia and sleepiness in Parkinson disease: associations with symptoms and comorbidities. AB - STUDY OBJECTIVES: Insomnia and daytime sleepiness are common complaints in Parkinson disease (PD), but the main causes remain unclear. We examined the potential impact of both motor and non-motor symptoms of PD on sleep problems. METHODS: Patients with PD (n = 128) were assessed using the Insomnia Severity Index, Epworth Sleepiness Scale, Unified Parkinson Disease Rating Scale, Beck Depression Inventory, Fatigue Severity Scale, Survey of Autonomic Symptoms, and the 39-item Parkinson Disease Questionnaire. A subset of subjects (n = 38, 30%) also completed nocturnal polysomnography and a multiple sleep latency test (MSLT). RESULTS: Multivariate stepwise logistic regression models revealed that subjective insomnia was independently associated with depressed mood (odds ratio [OR] = 1.79; 95% confidence interval (CI) [1.01-3.19]), autonomic symptoms (1.77 [1.08-2.90]), fatigue (1.19 [1.02-1.38]), and age (0.61 [0.39-0.96]). Subjective daytime sleepiness was associated with dosage of dopaminergic medication (1.74 [1.08-2.80]) and fatigue (1.14 [1.02-1.28]). On polysomnography, longer sleep latency correlated with autonomic symptoms (rho = 0.40, p = 0.01) and part I (non motor symptoms) of the Unified PD Rating Scale (rho = 0.38, p = 0.02). Decreased sleep efficiency correlated with autonomic symptoms (rho = -0.42, p < 0.0001). However, no significant difference emerged on polysomnography and MSLTs between patients with or without insomnia or daytime sleepiness. Higher rates of apneic events did predict shorter sleep latencies on the MSLTs. CONCLUSIONS: Non-motor symptoms appear to be associated with subjective insomnia, whereas fatigue and dopaminergic medication are associated with subjective daytime sleepiness. Objective sleep laboratory data provided little insight into complaints of insomnia and sleepiness, though obstructive sleep apnea predicted worsened sleepiness when measured objectively. PMID- 24235894 TI - Is there a first night effect on sleep bruxism? A sleep laboratory study. AB - STUDY OBJECTIVES: Sleep bruxism (SB) is reported to vary in frequency over time. The aim of this study was to assess the first night effect on SB. METHODS: A retrospective polysomnographic (PSG) analysis was performed of data from a sample of SB patients (12 females, 4 males; age range: 17-39 years) recorded in a sleep laboratory over 2 consecutive nights. Sleep parameters and jaw muscle activity variables (i.e., rhythmic masticatory muscle activity [RMMA]) for SB were quantified and compared between the 2 nights. Subjects were classified into groups according to severity of RMMA frequency, such as low frequency (2-4 episodes/h and/or < 25 bursts/h) and moderate-high frequency (>= 4 episodes/h and >= 25 bursts/h). RESULTS: Overall, no first night effects were found for most sleep variables. However, total sleep time, sleep efficiency, and stage transitions showed significant time and group interactions (repeated measures ANOVAs, p <= 0.05). The RMMA episode index did not differ between the 2 nights, whereas the second night showed significantly higher burst index, bruxism time index, and mean burst duration (repeated measure ANOVAs, p <= 0.05). Five patients of 8 in the low frequency group were classified into the moderate-high frequency group on the second night, whereas only one patient in the moderate high frequency group moved to the low frequency group. CONCLUSIONS: The results showed no overall first night effect on severity of RMMA frequency in young and healthy patients with SB. In clinical practice, one-night sleep recording may be sufficient for moderate-high frequency SB patients. However, low RMMA frequency in the first night could be confirmed by a second night based on the patient's medical and dental history. PMID- 24235895 TI - Correspondence between reported and actigraphic sleep measures in preschool children: the role of a clinical context. AB - STUDY OBJECTIVES: The aim of this study was to assess the role of clinical context in determining the correspondence between actigraphic and reported sleep measures in preschool children. METHODS: Sleep was assessed using actigraphy and parental reports in a clinical sample of 109 preschool children between the ages 4 and 6 years suffering from significant nighttime fears and in a sample of 30 healthy controls. RESULTS: In comparison to actigraphy, parents in both groups indicated that their children fell asleep earlier and overestimated their sleep period. These gaps were significantly larger in the control group than the clinical group. Parents from both groups similarly underestimated the time their child was awake during the night in comparison to actigraphy. Significant correlations were found in both groups between parental reports and actigraphy sleep schedule measures. Low correlations were found for wake after sleep onset in both groups and for the number of night wakings. CONCLUSIONS: Clinicians and researchers should be highly aware that parental reports on their children's sleep may not be accurate, and that accuracy may be affected by the context of the study. The use of complimentary sleep assessment tools in clinical and research settings should be encouraged. PMID- 24235896 TI - The Parent-Child Sleep Interactions Scale (PSIS) for preschoolers: factor structure and initial psychometric properties. AB - STUDY OBJECTIVES: Given the high prevalence of sleep problems in early childhood and the significant impact of parenting on children's sleep, the current study aimed to determine the factor structure and psychometric properties of a new measure for assessing sleep-related parenting behaviors and interactions among preschool-aged children-The Parent-Child Sleep Interactions Scale (PSIS). METHODS: Data was collected among parents of 209 preschool-aged children in two diverse metropolitan areas. All parents completed demographic questionnaires, the Parent-Child Sleep Interaction Scale (PSIS), and the Child Behavior Checklist (CBCL). A subset of parents completed structured interviews using the Preschool Age Psychiatric Assessment (PAPA). Following data reduction procedures, exploratory factor analysis (EFA) using principal axis extraction and oblique rotation was conducted, and internal consistency was assessed. Associations between PSIS scores and sleep problems based on the CBCL and PAPA as well as child sleep problems during infancy were examined. Differences based on demographic variables including race/ethnicity were also investigated. RESULTS: EFA revealed a three-factor solution explaining 60% of the variance in total PSIS scores. Individual factors based on 12 items were labeled Sleep Reinforcement, Sleep Conflict, and Sleep Dependence. Internal consistency for all subscales and total PSIS scores was acceptable. PSIS subscales were positively correlated with both CBCL and PAPA Sleep Problems. Sleep problems during the first year of life were associated with Sleep Conflict and total PSIS scores. Significant differences in PSIS scores based on race/ ethnicity were found. CONCLUSIONS: The PSIS shows promise as a valid measure of sleep-related parent/child behaviors and interactions among preschoolers. PMID- 24235897 TI - Acoustic pharyngometry measurement of minimal cross-sectional airway area is a significant independent predictor of moderate-to-severe obstructive sleep apnea. AB - STUDY OBJECTIVES: The current gold-standard method of diagnosing obstructive sleep apnea (OSA) is polysomnography, which can be inefficient. We therefore sought to determine a method to triage patients at risk of OSA, without using subjective data, which are prone to mis-reporting. We hypothesized that acoustic pharyngometry in combination with age, gender, and neck circumference would predict the presence of moderate-to-severe OSA. METHODS: Untreated subjects with suspected OSA were recruited from a local sleep clinic and underwent polysomnography. We also included a control group to verify differences. While seated in an upright position and breathing through the mouth, an acoustic pharyngometer was used to measure the minimal cross-sectional area (MCA) of the upper airway at end-exhalation. RESULTS: Sixty subjects were recruited (35 males, mean age 42 years, range 21-81 years; apnea-hypopnea index (AHI) 33 +/- 30 events/h (mean +/- standard deviation), Epworth Sleepiness Scale score 11 +/- 6, body mass index 34 +/- 8 kg/m(2)). In univariate logistic regression, MCA was a significant predictor of mild-no OSA (AHI < 15). A multivariate logistic regression model including MCA, age, gender, and neck circumference significantly predicted AHI < 15, explaining approximately one-third of the total variance (chi(2)(4) = 37, p < 0.01), with only MCA being a significant independent predictor (adjusted odds ratio 54, standard error 130; p < 0.01). CONCLUSIONS: These data suggest that independent of age, gender, and neck size, objective anatomical assessment can significantly differentiate those with mild versus moderate-to-severe OSA in a clinical setting, and may have utility as a component in stratifying risk of OSA. PMID- 24235898 TI - Obstructive sleep apnea severity is associated with left ventricular mass independent of other cardiovascular risk factors in morbid obesity. AB - OBJECTIVE: To evaluate the relation between obstructive sleep apnea (OSA) and left ventricular mass (LVM) in morbid obesity and the influence of gender, menopausal status, anthropometry, body composition, hypertension, and other cardiovascular risk factors in this relationship. DESIGN: Cross-sectional descriptive study. METHODS: Polysomnographic and echocardiographic studies were performed in a cohort of 242 patients (86 men, 100 premenopausal (PreM) and 56 postmenopausal (PostM) women), with grade II obesity and above (BMI: 43.7 +/- 0.4 kg/m(2)) to investigate OSA and LVM respectively. Anthropometry, body composition, glucose tolerance, and blood pressure were also recorded. RESULTS: OSA to different degrees was diagnosed in 76.2% of the patients (n: 166), its prevalence being 90.9% (n: 70) for men, and 76% (n: 38) and 63.8% (n: 58) for PostM and PreM women, respectively (p < 0.01). LVM excess was greatest for PostM women (90.2%), followed by men (81.9%) and PreM females (69.6%) (p < 0.01). LVM values increased in accordance to OSA severity (absence, 193.7 +/- 6.9 g; mild, 192.6 +/- 7.8 g; moderate, 240.5 +/- 12.5 g; severe, 273.6 +/- 14.6 g; p < 0.01). LVM magnitude correlated with the menopausal state, age, central adiposity, hypertension (HT), type 2 diabetes (DM), desaturation index (DI), and apnea hypopnea index (AHI) (r = 0.41; p < 0.01). The relationship between LVM and AHI persisted in the multivariate analysis (beta = 0.25; p < 0.05) after adjusting for age, gender, menopausal state, BMI, waist circumference, neck circumference, DI, fasting plasma glucose, DM, and HT. But if tobacco habits are included, the statistical difference disappears (beta = 0.22; p = 0.06). CONCLUSIONS: Morbid obesity is frequently associated with abnormal LVM, particularly in patients with OSA; this association is independent of HT, BMI, body composition, and other clinical factors, supporting a direct role of OSA on LVM in morbid obesity. This suggests that OSA and LVM might be taken as predictors of the cardiovascular risk in these patients. PMID- 24235899 TI - Prevalence and symptoms of occult sleep disordered breathing among older veterans with insomnia. AB - STUDY OBJECTIVES: To determine the prevalence of occult sleep disordered breathing (SDB) and describe the relationship between classic SDB symptoms (e.g., loud snoring) and occult SDB in older veterans with insomnia. METHODS: We analyzed baseline survey and in-home sleep study data for 435 veterans (mean age = 72.0 years [SD 8.0]) who had no known history of SDB, met International Classification of Sleep Disorders 2(nd) Edition criteria for insomnia, and were enrolled in a behavioral intervention trial for insomnia. Variables of interest included apnea-hypopnea index (AHI) >= 15, age, race/ethnicity, marital status, body mass index (BMI), insomnia subtype (i.e., onset, maintenance, or terminal), self-reported excessive daytime sleepiness, snoring, and witnessed breathing pause items from the Berlin Questionnaire. We computed the frequency of AHI >= 15 and assessed whether each classic SDB symptom was associated with an AHI >= 15 in 4 separate multivariate logistic regression models. RESULTS: Prevalence of AHI >= 15 was 46.7%. Excessive daytime sleepiness (adjusted odds ratio 1.63, 95% CI 1.02, 2.60, p = 0.04), but not snoring loudness, snoring frequency, or witnessed breathing pauses was associated with occult SDB (AHI >= 15). Insomnia subtypes were not significantly associated with occult SDB (p > 0.38). CONCLUSIONS: In our sample of older veterans with insomnia, nearly half had occult SDB, which was characterized by reported excessive daytime sleepiness, but not loud or frequent snoring or witnessed breathing pauses. Insomnia subtype was unrelated to the presence of occult SDB. PMID- 24235900 TI - Palatal sensory threshold reflects nocturnal hypoxemia and airway occlusion in snorers and obstructive sleep apnea patients. AB - STUDY OBJECTIVES: Upper airway sensory deficit has been reported to be associated with snoring or obstructive sleep apnea. There are limited data on the correlation between disease severity and upper airway sensation. In this study, we investigated the relationship between clinical parameters and standardized palatal sensory threshold (SPST) using Semmes Weinstein monofilaments. METHODS: We recruited 40 snorers and 19 control subjects. Palatal sensory threshold was measured in all study subjects, using Semmes Weinstein monofilaments. Standardized palatal sensory threshold was determined by subtraction of hard palate sensation from uvular sensation. All subjects with snoring underwent a modified Muller maneuver during wakefulness before polysomnography. RESULTS: SPST was higher in snorers than in control subjects, but did not differ according to the severity of obstructive sleep apnea. Patients with higher SPST (>= 0.45 g/mm(2)) were older and had more severe hypoxemia indices: lower nadir oxyhemoglobin saturation (SpO2) and higher percentage of sleep time at < 90% SpO2. Adjusted for age, sex, neck circumference, and body mass index, SPST was correlated with the apnea-hypopnea index and hypoxemia indices. With a cutoff value >= 0.45 g/mm(2), the sensitivity of SPST for nocturnal hypoxemia (nadir SpO2, < 80%) was 81.3%. Patients with higher SPST (>= 0.45 g/mm(2)) showed more airway occlusion in modified Muller maneuver, than those with lower values. CONCLUSIONS: The SPST measured using Semmes Weinstein monofilaments reflects nocturnal hypoxemia and airway occlusion. This test provides a potential tissue marker of the severity of hypoxemia in patients who snore. PMID- 24235902 TI - The complexities of complex sleep apnea. PMID- 24235901 TI - Air leak during CPAP titration as a risk factor for central apnea. AB - OBJECTIVES: Emergence of central sleep apnea has been described in the setting of continuous positive airway pressure (CPAP) initiation. The underlying mechanism is unclear; however, we postulate that air leak washing out anatomical dead space is a contributing factor. DESIGN: Data were obtained from 310 patients with obstructive sleep apnea (OSA) who underwent either split-night or full-night CPAP titration during January to July of 2009. The majority (n = 245) underwent titration with a nasal mask. Average total leak and maximum total leak were measured at therapeutic CPAP level. Unintentional leak was calculated by subtracting manufacturer-defined intentional leak from maximum leak. RESULTS: SUBJECTS WERE DIVIDED INTO TWO GROUPS: central apnea index (CAI) during titration < 5/hour and >= 5/hour. The groups were similar in terms of gender, age, BMI, and AHI. The CAI < 5 group had a median average leak of 45.5 L/min (IQR 20.8 L/min) versus 51.0 L/min (IQR 21.0 L/min) with CAI >= 5 (p = 0.056). Maximum leak was 59.5 L/min (IQR 27.0 L/min) with CAI < 5 and 75.0 L/min (IQR 27.8 L/min) with CAI >= 5 (p = 0.003). In the subset of subjects titrated using a nasal mask, median average leak was 42.0 L/min (IQR 17.0) in the CAI < 5 group and 50.0 L/min (IQR 16.8) in the CAI >= 5 group (p = 0.001). In the CAI < 5 group, median maximum leak was 57.0 L/min (IQR 23.0) versus 74.5 L/min (IQR 24.3) in the CAI >= 5 group (p < 0.001). CONCLUSIONS: Leak during CPAP titration is associated with the development of acute central apnea; these data may have mechanistic and therapeutic implications for complex apnea. COMMENTARY: A commentary on this article appears in this issue on page 1193. PMID- 24235903 TI - Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. AB - STUDY OBJECTIVE: Sleep hygiene recommendations are widely disseminated despite the fact that few systematic studies have investigated the empirical bases of sleep hygiene in the home environment. For example, studies have yet to investigate the relative effects of a given dose of caffeine administered at different times of day on subsequent sleep. METHODS: This study compared the potential sleep disruptive effects of a fixed dose of caffeine (400 mg) administered at 0, 3, and 6 hours prior to habitual bedtime relative to a placebo on self-reported sleep in the home. Sleep disturbance was also monitored objectively using a validated portable sleep monitor. RESULTS: Results demonstrated a moderate dose of caffeine at bedtime, 3 hours prior to bedtime, or 6 hours prior to bedtime each have significant effects on sleep disturbance relative to placebo (p < 0.05 for all). CONCLUSION: The magnitude of reduction in total sleep time suggests that caffeine taken 6 hours before bedtime has important disruptive effects on sleep and provides empirical support for sleep hygiene recommendations to refrain from substantial caffeine use for a minimum of 6 hours prior to bedtime. PMID- 24235904 TI - Patient safety incidents during overnight polysomnography: a five-year observational cohort study. AB - INTRODUCTION: Attended polysomnography (PSG) is a common procedure and is regarded as relatively safe. There have been few systematic evaluations of adverse events occurring during PSG. An understanding of the frequency and type of the adverse events during PSG should inform risk mitigation plans and the development of guidelines for sleep center accreditation. We aimed to identify, tabulate, and classify all adverse events that occurred during overnight PSG conducted at an accredited sleep center over a five-year period. METHODS: All adverse events occurring from Jan 1, 2005, to Dec 31, 2010, at the Center for Sleep Medicine, Mayo Clinic, were identified. Information was collated from calls made to emergency responders, to the adverse event reporting system, and events forwarded to the medical director. RESULTS: A total of 36,141 PSGs were performed over the study duration. Fifty-eight adverse events occurred during the study period (1 event/623 PSGs). Most adverse events were cardiac in nature (17/58; 29.3%), a majority involving acute chest pain. Falls were the next most common (20.6%), followed by neurologic (8.6%), pulmonary (3.4%), and psychiatric (3.4%) events. The rest were classified as miscellaneous. There were no patient deaths during PSGs. The majority of patients experiencing an adverse event were transported to the emergency room (37/58; 63.79%). Of these, 15/37 (40.54%) were admitted to the hospital, and 3 required an ICU bed. CONCLUSION: Adverse events during a PSG were relatively uncommon. Previous emphasis on cardiac arrhythmias may be overstated, as chest pain and patient falls were commonest and resulted in hospitalization more often. PMID- 24235905 TI - Disconnection between periodic leg movements and cortical arousals in spinal cord injury. AB - OBJECTIVE: In this study we examine the temporal connection between periodic leg movements (PLMs) and cortical arousals, as well as the treatment effect of pramipexole, in a clinical case with spinal cord lesion. METHODS: A patient with complete cervical spinal cord injury and PLMs during sleep underwent two baseline sleep recordings, one recording with dopaminergic treatment, and one recording with adaptive servoventilation. RESULTS: The PLMs were temporally dissociated from cortical arousals as well as from respiratory or heart rate events. PLMs were suppressed by pramipexole and persisted after treatment of apnea. CONCLUSION: The disconnection of PLMs from arousals supports a spinal generator or peripheral trigger mechanism for PLMs. The suppression of movements by a dopamine agonist suggests that its site of action is caudal to the cervical lesion and outside of the brain. Our observation provides significant new knowledge about the pathogenesis of PLMs and warrants studies in larger populations. PMID- 24235906 TI - Kleine-levin syndrome treated with clarithromycin. AB - Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by periodic hypersomnia and various degrees of cognitive and behavioral disturbance, hyperphagia, and hypersexuality. Effective treatment is challenging. Stimulants marginally address sleepiness, but may increase irritability and do not improve cognitive and behavioral disturbances. Modafinil may shorten the symptomatic period but not the recurrence rate. Lithium and carbamazepine are beneficial in some cases, possibly related to similarities between KLS and affective disorders. Currently, no single medication is consistently successful in treating the syndrome. Here we report the short-term effect of clarithromycin in a patient with KLS. PMID- 24235908 TI - Can you hear me snore? PMID- 24235907 TI - The relationship between depressive symptoms and obstructive sleep apnea in pediatric populations: a meta-analysis. AB - BACKGROUND: A higher incidence of depressive disorders and symptoms has been suggested among children suffering from obstructive sleep apnea (OSA). Yet, the extent to which OSA is related to increased depression is unclear. OBJECTIVES: To evaluate (a) the relationship between depressive symptoms and OSA in pediatric populations, and (b) the efficacy of adenotonsillectomy (AT) for decreasing depressive symptoms among children with OSA. METHODS: A meta-analysis was conducted to assess the relationship between depressive symptoms and OSA, and the efficacy of AT for decreasing depressive symptoms. Studies reporting depressive symptoms of children with OSA through January 2013 were included. RESULTS: Eleven studies assessed depressive symptoms in both children diagnosed with OSA (n = 894) and a comparison group (n = 1,096). A medium relationship was found between depressive symptoms and OSA (Hedges' g = 0.43, 95% CI: 0.22-0.64; p = 0.0005). Addressing the second question, 9 studies (n = 379 children) examined depressive symptoms pre- and post-AT. A medium improvement in depressive symptoms was found at follow-up (Hedge's g = 0.41, 95% CI: 0.20-0.62; p <= 0.001). CONCLUSION: Our findings suggest that depressive symptoms are higher among children with OSA. Therefore, patients with depressive symptomatology should receive screening for sleep disordered breathing. Treatment of OSA with AT might decrease clinical symptoms of depression, reduce pharmacotherapy, improve sleep patterns, and promote better health. PMID- 24235909 TI - Adenotonsillectomy or watchful waiting in the management of childhood obstructive sleep apnea. PMID- 24235910 TI - Preparation, Characterization, and Antimicrobial Activities of Bimetallic Complexes of Sarcosine with Zn(II) and Sn(IV). AB - Heterobimetallic complexes of Zn(II) and Sn(IV) with sarcosine have been synthesized at room temperature under stirring conditions by the reaction of sarcosine and zinc acetate in 2 : 1 molar ratio followed by the stepwise addition of CS2 and organotin(IV) halides, where R = Me, n-Bu, and Ph. The complexes were characterized by elemental analysis, FT-IR and NMR ((1)H, (13)C) spectroscopy. IR data showed that the ligand acts in a bidentate manner. NMR data revealed the four coordinate geometry in solution state. In vitro antimicrobial activities data showed that complexes (3) and (4) were effective against bacterial and fungal strains with few exceptions. PMID- 24235911 TI - Biosorption of Arsenic(III) from Aqueous Solutions by Modified Fungal Biomass of Paecilomyces sp. AB - The biosorption of As(III) on iron-coated fungal biomass of Paecilomyces sp. was studied in this work. It was found that the biomass was very efficient removing the metal in solution, using Atomic Absorption, reaching the next percentage of removals: 64.5%. The highest adsorption was obtained at pH 6.0, at 30 degrees C after 24 hours of incubation, with 1 mg/L of modified fungal biomass. PMID- 24235912 TI - A Behavior Analytic Interpretation of Theory of Mind. AB - The inference that others are subject to private events is almost universal among humans. Since no one has direct access to another person's private events, we have proposed this inference occurs because of: 1) The almost simultaneous occurrence a child's private kinesthetic stimuli and the visual stimuli produced by another person's motor act during imitation of motor acts; 2) The similarity between the child's vocal behavior and that of another person during vocal imitation; and 3) The stimulus equivalence that occurs when the child's behavior and similar behavior of others are given the same name. We have proposed that perspective taking is a very common activity in our daily lives and that performance on false belief tests is a special case of perspective taking. In our analysis of the prerequisites for successful predictions on false belief tests we have considered false belief tests as primarily predictions concerning the behavior of others in situations in which discriminative stimuli are available to the child being tested and not to the protagonist about whom the child is to make a prediction. Predictions about other's behavior are made on the basis of three types of prior observations and descriptions: (a) observation and descriptions of the behavior of a specific individual in similar situations; (b) observation and descriptions of the behavior of many different people in similar situations; and (c) observation and descriptions of one's own behavior in similar situations. Success on the false belief tests necessitates discrimination between the stimuli available to the child and those available to the protagonist. PMID- 24235913 TI - Effects of protein energy supplementation during pregnancy on fetal growth: a review of the literature focusing on contextual factors. AB - BACKGROUND: Maternal diet during pregnancy is one of the most important factors associated with adequate fetal growth. There are many complications associated with fetal growth restriction that lead to lifelong effects. The aim of this review was to describe the studies examining the effects of protein energy supplementation during pregnancy on fetal growth focusing on the contextual differences. METHODS: Relevant articles published between 2007 and 2012 were identified through systematic electronic searches of the PubMed, Science Direct, and EBSCO database and the examination of the bibliographies of retrieved articles. The search aimed to identify studies examining pregnant women receiving protein and/or energy during pregnancy and to assess fetal growth measures. Data of effectiveness and practical aspects of protein energy supplementation during pregnancy were extracted and compiled. RESULTS: Twenty studies (11 randomized controlled trials, 8 controlled before and after, and 1 prospective study) were included in this review. Positive outcomes in infants and women cannot be expected if the supplementation is not needed. Therefore, it is essential to correctly select women who will benefit from dietary intervention programs during pregnancy. However, there is currently no consensus on the most effective method of identifying these women. The content of protein in the supplements considering total diet is also an important determinant of fetal growth. Balanced protein energy supplementation (containing up to 20% of energy as protein) given to pregnant women with energy or protein deficit appears to improve fetal growth, increase birth weight (by 95-324 g) and height (by 4.6-6.1 mm), and decrease the percentage of low birth weight (by 6%). Supplements with excess protein (>20% of energy as protein) provided to women with a diet already containing adequate protein may conversely impair fetal growth. There is also no consensus on the best time to start supplementation. CONCLUSIONS: Strong quality studies examining adequate criteria to screen women who would benefit from supplementation, time to start supplementation, and type of supplements are warranted. PMID- 24235914 TI - Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa. AB - BACKGROUND: Repetitive involuntary head nodding was first reported in the 1960s in the Wapogoro tribe of Tanzania. OBJECTIVES: We describe the natural history of head nodding in the Wapogoro tribe, with special reference to the earliest reported dates of onset. METHODS: We analyzed clinical data from 150 historical patients seen between 1960 and 1971. RESULTS: Head nodding with or without grand mal convulsions was present in 33/150 (~20%) cases, was mostly familial and equally distributed by gender. Age at onset of head nodding ranged from 2-22 years (mean: ~10 years) in the period 1934-1962. Head nodding preceded onset of grand mal convulsions by up to 12 months, and motor and psychomotor deficits indicative of brain damage developed with time. Fourteen of the 33 cases died at 13-39 years of age (mean: ~20 years) while nineteen aged 16-28 years (mean: ~16 years) were still alive. CONCLUSION: Historical accounts of head nodding (amesinzia kichwa, Swahili) among the Wapogoro tribe fit the August 2012 World Health Organization (WHO) case definition of probable Nodding Syndrome. Reported to have existed in this population for at least 80 years, Nodding Syndrome is a progressive seizure disorder that leads to generalized convulsions (kifafa), brain damage and death. PMID- 24235916 TI - Neuropsychiatric perspectives on nodding syndrome in northern Uganda: a case series study and a review of the literature. AB - BACKGROUND: Nodding Syndrome (NS), previously called Nodding Disease, is a chronic and debilitating illness affecting thousands of children aged 3-18 years in post-conflict Northern Uganda and South Sudan. Characterised by malnutrition, stunted growth, mental retardation and seizures, some researchers have designated it as epilepsy. With reports appearing in Northern Uganda in1997, NS reached epidemic proportions around 2000-2003 when people were moved into Internally Displaced People's (IDP) camps. Investigations for infections (onchocerciasis) and toxins have been inconclusive as to cause, treatment or outcome. No study has addressed the possible relationship of NS to childhood war-trauma experiences. OBJECTIVE: To explore a possible relationship of exposure to prolonged war-trauma and the emergence of epidemic NS in Northern Uganda. METHOD: This study was a case-series descriptive psychiatric naturalistic field observations of NS cases from homesteads in Northern Uganda and psychiatric investigations and treatment of NS cases referred to Mulago National Referral and Teaching Hospital. RESULTS: Detailed Psychiatric clinical evaluations and field observations revealed that NS children had been exposed to severe war-related psychological and physical trauma as well as non-specific CNS insults including untreated CNS infections/infestations and malnutrition possibly causing seizures. Many children suffered post-traumatic stress disorder (PTSD) and depression. CONCLUSION: NS could present as an association of childhood complex PTSD, (called Developmental Trauma Disorder), occurring in the chronically war-traumatised children of Northern Uganda, complicated by severe prolonged depression with its characteristic symptoms of psychomotor retardation, anxiety, anhedonia and anorexia. This, coupled with food shortages, resulted in malnutrition, wasting and stunted growth with severe avitaminoses. Many children had seizures. All this calls for multi-disciplinary treatment approaches. PMID- 24235915 TI - Nodding syndrome in Mundri county, South Sudan: environmental, nutritional and infectious factors. AB - BACKGROUND: Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda. OBJECTIVE: To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001. METHODS: Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001-2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan. RESULTS: Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded. CONCLUSION: Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food. PMID- 24235917 TI - Proposed guidelines for the management of nodding syndrome. AB - Nodding Syndrome is a poorly understood neurologic disorder of unknown aetiology that affects children and adolescents in Africa. Recent studies have suggested that the head nods are due to atonic seizures and Nodding Syndrome may be classified as probably symptomatic generalised epilepsy. As part of the Ugandan Ministry of Health clinical management response, a multidisciplinary team developed a manual to guide the training of health workers with knowledge and skills to manage the patients. In the absence of a known cause, it was decided to offer symptomatic care. The objective is to relieve symptoms, offer primary and secondary prevention for disability and rehabilitation to improve function. Initial management focuses on the most urgent needs of the patient and the immediate family until 'stability' is achieved. The most important needs were considered as seizure control, management of behavioural and psychiatric difficulties, nursing care, nutritional and subsequently, physical and cognitive rehabilitation. This paper summarises the processes by which the proposed guidelines were developed and provides an outline of the specific treatments currently being provided for the patients. PMID- 24235918 TI - Evaluation of patients with Crimean-Congo hemorrhagic fever in Bolu, Turkey. AB - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF), which is associated with a high mortality rate in the Black Sea region of Turkey, has received increasing attention. OBJECTIVE: In this study, the epidemiological features, clinical and laboratory findings, treatments, and outcomes of patients diagnosed with CCHF between 2006 and 2012 based on data obtained from the Bolu Provincial Directorate of Health (BPDH) were evaluated. METHODS: BPDH data were reviewed for the period between 1 January 2006 and 31 July 2012. The locations where the tick had attached to the patient, the site of the tick bite on the patient's body, the dates of tick bite and removal, and the demographic characteristics of each patient were recorded. BPDH data on the total number of tick bites, patients with confirmed CCHF, and deaths due to CCHF in Bolu Province during the study period were also evaluated. RESULTS: A total of 46 patients with CCHF and 38 patients without CCHF but who had been bitten by ticks were admitted to the BPDH. Of the patients with CCHF, 54.3% were female. The mean age of the patients was 46.88 +/- 2.05 years (range, 1-79 years). The mortality rate was 8.82%. Patients were predominantly observed in June and July. When the patients were distributed according to their occupations, the majority was houswife (48.6%), followed by animal husbandry worker (27.0%), farmer (10.8%), health worker (5.4%), and other (8.1%). The symptoms of the patients with CCHF included fatigue (60.9%), fever (60.9%), and myalgia (60.9%). Of those patients with CCHF, 41.3% were determined to have a high fever. CONCLUSIONS: The probability of developing CCHF decreased as the duration of tick attachment increased. Moreover, although the clinical presentation is important, it is not diagnostic. Physical examination and laboratory findings become more specific in later stages. PMID- 24235919 TI - Global analysis of differential expressed genes in ECV304 Endothelial-like cells infected with human cytomegalovirus. AB - BACKGROUND: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. OBJECTIVE: With the application of DNA microarrays, we could monitor the effects of pathogens on host cell gene expression programmes in great depth and on a broad scale. METHODS: Changes in mRNA expression levels of human endothelial-like ECV304 cells following infection with human cytomegalovirus AD169 strain was analyzed by a microarray system comprising 21073 60-mer oligonucleotide probes which represent 18716 human genes or transcripts. RESULTS: The results from cDNA microarray showed that there were 559 differential expressed genes consisted of 471 upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2 and LRRC28), and the results of which were consistent with those from the microarray. Among 237 biology processes, 39 biology processes were found to be related significantly to HCMV-infection. The signal transduction is the most significant biological process with the lowest p value (p=0.005) among all biological process which involved in response to HCMV infection. CONCLUSION: Several of these gene products might play key roles in virus-induced pathogenesis. These findings may help to elucidate the pathogenic mechanisms of HCMV caused diseases. PMID- 24235920 TI - Baboons as potential reservoirs of zoonotic gastrointestinal parasite infections at Yankari National Park, Nigeria. AB - BACKGROUND: Zoonoses pose a risk to public health. OBJECTIVE: To carry out the investigation of the prevalence of gastrointestinal parasites of baboons, Papio anubis, frequenting the Wikki base Camp in Yankari National Park, Nigeria. METHOD: Formol-ether concentration technique was used to isolate parasite eggs and cysts from faecal samples. RESULTS: Parasites recovered were Ascaris lumbricoides, Ancylostoma duodenale, Strongyloides stercoralis, Fasciola sp, Schistosoma mansoni, Hymenolepis nana, and Trichostrongylus sp, and cysts of protozoan parasites Entomoeba histolytica, E. coli, and Iodamoeba butschii. CONCLUSION: Most of the parasites identified are known to have high pathologic involvement in humans, implicating the baboons as potential source and reservoirs for human zoonotic parasitic infections although further molecular work would be necessary to ascertain if these gastrointestinal parasites are the same strains that infect humans. PMID- 24235921 TI - Hepatitis C and blood transfusion among children attending the Sickle Cell Clinic at Mulago Hospital, Uganda. AB - BACKGROUND: Hepatitis C virus (HCV) accounts for 90% of post-transfusion hepatitis. In Uganda, there has been limited research of prevalence of HCV among sickle cell anaemia (SS) patients, a group at risk for multiple transfusions. OBJECTIVES: To establish prevalence of HCV infection and determine whether blood transfusion increases risk among SS patients. METHODS: 244 SS patients aged 1-18 years were recruited by consecutive sampling. Socio-demographic, clinical and transfusion history was collected. Clinical examination done and blood tested for HCV by MEIA. RESULTS: 244 children were recruited. Of these, 159 (65%) had a history of blood transfusion. Among the transfused, five patients were HCV positive. Four of these were over 12 years of age. Among patients with no history of transfusion, one patient aged 14 years was HCV positive. Risk of HCV was higher among the transfused OR 2.7(CI 0.31-24). Patients who received more than two units were more likely to be HCV positive (p=0.03). CONCLUSIONS: HCV prevalence of 2.5% was low but higher than that reported by other investigators in Uganda. Blood transfusion was a major contributing factor in occurrence of HCV. Children who get repeated transfusions should be screened for Hepatitis C and screening of blood for HCV prior to transfusion would help reduce occurrence of the disease. PMID- 24235922 TI - Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. AB - BACKGROUND: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. OBJECTIVES: The study aimed at description of the pattern of IVIG use (label/off label indications), adverse effects observed, reason for choice of IVIG among other modalities and efficacy in a pediatric intensive care setting. METHODS: A retrospective chart review. PATIENTS: The study included 45 cases admitted from 2008 through 2011 in a Pediatric Intensive Care Unit (PICU) of a tertiary referral pediatric hospital. RESULTS: The clinical diagnoses included neurology (35%), neonatology (16%), hematology (11%), autoimmune disorders (11%) immunodeficiency disorders (11%), infections other than neonatal sepsis (9%) and cardiology (6.5 %). The indications for IVIG use had an Evidence category Ia / Ib in 62 % of cases whereas the other 38 % had level II and III evidence. Choice of IVIG as a therapeutic option was based on failure of other treatment options to achieve response in 46.5%, lack of alternative treatment options 15.5 % and the need for urgent response in 38 %. Adverse events, duration and doses are reported. CONCLUSION: IVIG use is governed by availability of alternative options and the need for urgent response in critically ill children. Guidelines should be issued based on locally available treatment options and their cost effectiveness. PMID- 24235923 TI - Is there a suburban sleeping sickness in Libreville? AB - BACKGROUND: The transmission of sleeping sickness occurs primarily in rural areas, and exposed populations are those living from rural activities such as agriculture, fishing, animal husbandry or hunting. However, urban and suburban foci are more and more reported in T. b. gambiense areas. In Libreville town, sleeping sickness cases are regularly diagnosed. In order to investigate about the establishment of a transmission cycle of that disease, we have carried out an entomological survey in two quarters in the vicinity of the town. METHODS: Vavoua traps were set out in all suitable biotopes for tsetse flies during four days and examined twice a day. Flies were collected, identified and dissected. RESULTS: Two species of Glossina were caught: G. palpalis palpalis (90.58%) and G. caliginea (9.42%). A total infection rate of 9.37% was observed after dissection of all non-teneral flies captured. CONCLUSION: These results suggest the establishment of a trypanosomiasis transmission cycle in the area. No salivary gland was found infected. Given that infected persons are regularly detected, we can think about the existence of a suburban sleeping sickness focus in Libreville. More analysis is needed concerning the identification of human trypanosomes and the origin of Glossina blood meals that may confirm the existence of that focus. PMID- 24235924 TI - HIV/AIDS knowledge among undergraduate university students: implications for health education programs in Ghana. AB - BACKGROUND: Globally, the spread of HIV/AIDS remains on the rise especially among adolescents who are at increased risk of infection. Sexual behavioural change remains one of the most effective ways of preventing further transmission among this vulnerable group. OBJECTIVE: To evaluate HIV/AIDS knowledge among undergraduate students' and how it can be used in HIV prevention strategies in Ghana. METHODS: A cross-sectional study was conducted using structured questionnaires among 324 conveniently selected students enrolled at a tertiary institution in Accra, Ghana. RESULTS: The mean age of the respondents was 23 years. Although the mean score of the participants' responses to 12 HIV/AIDS knowledge questions was 7.7 of 12 points, there was an inconsistent level of AIDS knowledge with significant gender difference. While students could identify the transmission modes and preventive measure, they were less knowledgeable about the causative agent of AIDS. Majority of the students reported having received AIDS information from both print and electronic media, but few of them received such information from parents. Although over 90% of the students knew where to access VCT services, 45% of them have not had HIV test. CONCLUSION: The data underscore the urgent need for HIV/AIDS-related health education and prevention efforts targeting university students as well as younger age groups in Ghana. PMID- 24235925 TI - The impact of HIV/AIDS stigma on HIV counseling and testing in a high HIV prevalence population in Uganda. AB - BACKGROUND: Despite its importance in HIV/AIDS prevention and treatment, HIV/AIDS Counseling and Testing (HCT) is low in sub-Saharan Africa, where the disease continues to be a serious public health problem. This has in part been attributed to HIV/AIDS related stigma. OBJECTIVE: To assess the level of HIV/AIDS related stigma and its impact on uptake of HCT in a high HIV prevalence population in Uganda. METHODS: The paper used cross-sectional data on 135 men and 185 women in reproductive ages. Data were analyzed using the Pearson's chi-square statistic and the random intercept binary logistic regression model to identify significant predictors of uptake of HCT. RESULTS: The result shows that only 18.4% of the respondents, most of them men expressed highly stigmatizing attitudes against PLHA and 59%, men and women alike, received HCT. Uptake of HCT was higher among men (OR=1.89, p<0.01) and women (OR=4.48, p <0.001) who expressed least stigmatizing attitudes. Secondary/higher education, work in the informal sector and being ever married were significant predictors of uptake of HCT. Compared to men, women aged 25-34, 35+ and with one sexual partner were more likely to have received HCT. CONCLUSIONS: The low level of stigma, older age, higher level of education, being ever married and monogamous sexual relationships are significant predictors of increased uptake of HCT. PMID- 24235926 TI - 24-Month adherence, tolerance and efficacy of once-a-day antiretroviral therapy with didanosine, lamivudine, and efavirenz in African HIV-1 infected children: ANRS 12103/12167. AB - BACKGROUND: There is no data on long-term benefit of once-a-day antiretroviral therapy (ART) with combination of DDI, 3TC and EFV to allow its use in future therapeutic strategies. OBJECTIVES: To assess 24-month immuno-virological, adherence, tolerance, and effectiveness of a once-a-day ART with DDI, 3TC and EFV. METHODS: A phase 2 open trial including 51 children aged from 30 months to 15 years, monitored a once-a-day regimen for 24 months from 2006 to 2008 in the Departement de Pediatrie du CHUSS, at Bobo-Dioulasso in Burkina Faso. We tested immunological and virological response, adherence, tolerance and resistance of the treatment. RESULTS: Children with CD4 >25% at 24 months were 67.4% (33/49) CI 95% [54%, 80%]. The proportion of children with viral plasma RNA <300 cp / ml at 24 months of treatment was 81.6 % (40/49) CI [68.0% 91.2%]. Good adherence was obtained with more than 88% adherence > 95% over the 24 months. Drugs were well tolerated. CONCLUSIONS: Given the limited number of antiretroviral drugs available in Africa and the inadequacy of laboratory monitoring in support program, once-a-day treatment and especially the DDI-based combination strategies could be an attractive operational option. PMID- 24235927 TI - Malaria and HIV co-infection and their effect on haemoglobin levels from three health-care institutions in Lagos, southwest Nigeria. AB - BACKGROUND: Malaria and human immunodeficiency virus (HIV) are two major infections with enormous public health consequence. Together, they are endemic in many developing countries with anaemia being the most frequent haematological consequence of the infections. OBJECTIVES: To determine the prevalence of malaria and HIV co-infection as well as anaemia among selected patients from three health care institutions in Lagos, Nigeria. METHODS: A cross-sectional study of 1080 patients was carried out to determine the prevalence of malaria and HIV co infection as well as anaemia. Blood sera from each of the patients were screened for malaria parasites, HIV-1 and HIV-2 using Giemsa stain, Cambridge Biotech Recombigen HIV-1/HIV-2 rapid device, respectively while haemoglobin estimation was performed using cyanmethemoglobin method. RESULTS: Our data showed that the total number of malaria infected patients were significantly higher in HIV sero positive patients 47.7% (31/65) when compared with their HIV sero-negative counterparts 25.8% (262/1015) P = 0.047. The result also revealed that 25.8% (8/31) of the patients co-infected with malaria and HIV had anaemia as compared to 11.1% (29/262) infected with malaria alone. Multivariable logistic regression analysis showed that patients with dual infection of malaria and HIV were twice likely to be anaemic than those infected with malaria alone [adjusted OR 2.4, 95% CI, 1.3 to 2.7, P = 0.014]. CONCLUSIONS: Our data indicated a higher prevalence of malaria in HIV infected patients and also revealed that patients co-infected with malaria and HIV were more likely to be anaemic. PMID- 24235928 TI - Factors affecting the HIV/AIDS epidemic: an ecological analysis of global data. AB - BACKGROUND: All over the world the prevalence of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) has became a stumbling stone in progress of human civilization and is a huge concern for people worldwide. OBJECTIVES: To determine the social and health factors which contribute to increase the size of HIV epidemic globally. METHODS: The country level indicators of HIV prevalence rates, are contraceptive prevalence rate, physicians density, proportion of Muslim populations, adolescent fertility rate, and mean year of schooling were compiled of 187 countries from the United Nations (UN) agencies. To extract the major factors from those indicators of the later five categories, backward multiple regression analysis was used as the statistical tool. RESULTS: The national HIV prevalence rate was significantly correlated with almost all the predictors. Backward multiple linear regression analysis identified the proportion of Muslims, physicians density, and adolescent fertility rate are as the three most prominent factors linked with the national HIV epidemic. CONCLUSION: The findings support the hypotheses that a higher adolescent fertility rate in the population is the adverse effect of premarital and extramarital sex that leads to longer period of sexual activity which increases the risk of HIV infection. On the hand, and cultural restrictions of Muslims and sufficient physicians will decelerate the spread of HIV infections in the society. PMID- 24235930 TI - Exotic and indigenous problem plants species used, by the Bapedi, to treat sexually transmitted infections in Limpopo Province, South Africa. AB - BACKGROUND: The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi. OBJECTIVES: To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge. METHODS: A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers. RESULTS: Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs. CONCLUSIONS: Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio economic vulnerable people. PMID- 24235929 TI - Personal barriers to antiretroviral therapy adherence: case studies from a rural Uganda prospective clinical cohort. AB - BACKGROUND: Although good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes, some patients may have specific personal barriers to ART adherence. OBJECTIVES: To study specific personal barriers to ART adherence. METHODS: Quantitative data on patients' health status, ART adherence, CD4 cell counts and viral loads were collected, and qualitative data on life experiences of five patients with poor ART outcomes and adherence were also collected. RESULTS: Out of 35 patients with poor immunological and virological ART outcomes, 17 (49%) also had poor ART adherence. Patient 1 had no living child and did not disclose her HIV serostatus to her spouse because she wanted to have a child. Patient 2 was an orphan with neither social nor family support. Patient 3 stopped ART when she conceived, returned to the study clinic when pregnant again and was sickly. She was switched to second-line ART with satisfactory outcomes. Patient 4, a 14 year old orphan had missed ART for 2 months when his treatment supporter was away. Patient 5 aged 66 years stopped ART which he blamed for his erectile dysfunction. CONCLUSION: ART adherence counselling should target specific personal barriers to ART adherence like: lack of family support, health and sexual life concerns, desire to have children and family instability. PMID- 24235931 TI - Developing antiviral surgical gown using nonwoven fabrics for health care sector. AB - BACKGROUND: Healthcare workers' uniforms including surgical gowns are used as barriers to eliminate the risk of infection for both doctor and patient. The prevalence of human immunodeficiency virus, hepatitis B and C viruses in the patient population is very common. OBJECTIVES: To develop antiviral surgical gown comprising of Polypropylene nonwoven as outer layer, Polytetrafluroethylene (PTFE) film as middle layer and polyester nonwoven as inner layer and the surgical gown with a basic weight of 70 g/m(2). METHODS: The titanium dioxide (TiO2) nano dispersion was prepared with methylene blue and urea as a reacting medium. These nano particles have an average size of 9 nm which was revealed by High resolution transmission electron microscope. The nonwoven fabric pore size was characterised by using digital image analyzer. The polypropylene nonwoven fabrics were treated with nano dispersion by pad-dry-cure method and trilaminate fabric was formed using fusing machine. The presence of nano particle on the surface of the non woven fabric was confirmed by Scanning Electron microscope. RESULTS: The trilaminate surgical gown has passed ASTM 1671 viral penetration test which is mandatory for healthcare facilities. The average pore size of inner, middle and outer layer were found as 0.187, 0.4 and 0.147 micron respectively. The tensile strength of the trilaminate fabric in both machine and cross direction was 145 N and 94 N respectively. The tearing strength of the trilaminate fabric in direction I and II was 10 N and 4 N respectively. The hydrostatic and index puncture resistance of the trilaminate fabric was 2930 mmwc and 58.8 N respectively. The moisture vapour permeability of the fabric was exhibited as 585.7 g/m(2)/day. CONCLUSIONS: The surgical gown exhibits antiviral property which can protect the health care people from human immunodeficiency virus. PMID- 24235932 TI - Effect of severe sepsis on platelet count and their indices. AB - BACKGROUND: Sepsis is a major disease affecting almost all organs and systems. OBJECTIVES: To examine platelet count and indices (mean platelet volume (MPV) and platelet distribution width (PDW)) in severe sepsis. METHODS: Patients with criteria for sepsis at a first examination by an Infectious Diseases specialist were selected. Consecutive patients who were admitted to the out-patient clinic and who were not diagnosed with any infectious disease were selected as the control group. RESULTS: A total of 145 patients with sepsis and 143 patients as a control group were included in the study. MPV and PDW were significantly differentbetween sepsis patients and control group (P<0.05). Platelet count in sepsis patients was lower than control group but the difference was not significant. PDW was the unique significantly different parameter between survivors and non-survivors (p=0.001). CONCLUSION: Platelet indices are important laboratory findings in the diagnosis of sepsis and severe sepsis. Severe sepsis patients who have greater than 18 % PDW levels have a higher risk of death. Therefore, PDW, which is part of an inexpensive, easily accessible and routinely performed test for almost all patients admitted to health facilities may be used for predicting mortality. PMID- 24235933 TI - Relationship between climate conditions and nosocomial infection rates. AB - BACKGROUND: Nosocomial infections constitute a global health problem. OBJECTIVES: To explore the relationship between nosocomial infection rates (NIRs) and climatic factors including temperature and relative humidity in Guangzhou area of China. METHODS: 30892 patients in our hospital in 2009 were investigated for nosocomial infection status, and the contemporaneous temperature and relative humidity were analyzed statistically. NIRs increased with relative humidity and temperature in central ICU and geriatric department. RESULTS: No statistical differences were found between each quarter of 2009 in the distribution of nosocomial infection sites. There were no statistical differences in the pathogenic species of nosocomial infections between high-temperature and low temperature months in different departments. NIRs had a correlation with temperature and relative humidity in geriatric department and central ICU. CONCLUSIONS: To decrease NIRs and improve health care quality, it is necessary to strengthen the control of temperature and humidity especially for geriatric department and central ICU. PMID- 24235934 TI - Healthcare providers' attitudes and perceptions in infection diagnosis and antibiotic prescribing in public health institutions in Lesotho: a cross sectional survey. AB - BACKGROUND: The decision to prescribe antibiotics and the selection of an appropriate antibiotic are important in the treatment of infectious diseases. As any human decision, it can be influenced by individual attitudes and perceptions. OBJECTIVES: To assess the attitudes and perceptions of healthcare providers regarding antibiotic prescribing and the use of laboratory results in infection diagnosis. METHODS: A cross sectional survey in five selected Health Service Areas (HSAs) in the Southern Africa country of Lesotho. The questionnaires were self-administered to 67 healthcare providers in public health institutions within the selected HSAs. Data were analyzed using Fisher's exact test or the McNemar Test for dependent proportions. RESULTS: 51 surveys were returned (39 medical doctors, 12 nurses). Respondents typically practiced in urban settings, worked with both inpatients and outpatients, had over 10 years experience, and attended to at least 26 patients per day. We identify several inappropriate practices related to the use of on-site microbiology laboratories. For example, only 17% always send a sample for microscopic identification prior to prescribing antibiotics and only 32% always send a sample for culture sensitivity tests. Delays in obtaining laboratory results and high patient workloads were cited as reasons for under-utilization of laboratory facilities. Nearly all respondents recognize the need for guidelines and further training in antibiotic prescribing. CONCLUSION: Healthcare providers demonstrated attitudes and perceptions in antibiotic prescribing or use of laboratory derived information in infection diagnosis that could have negative impacts on antibiotic prescribing. PMID- 24235935 TI - A 5 - year surveillance of wound infections at a rural tertiary hospital in Nigeria. AB - BACKGROUND: Wound infections are associated with increased morbidity and mortality. OBJECTIVES: To determine the prevalence, aetiology and susceptibility profile of bacterial agents of wound infection among in- and- out patients at a rural tertiary hospital in Nigeria, within a 5 year period. METHODS: Wound swabs collected from 156 out-patients and 353 in-patients were, cultured and microbial isolates identified using standard methods. Antibiotic susceptibility testing was done on bacterial isolates. RESULTS: The prevalence of wound infection in 2006, 2007, 2008, 2009 and 2010 was 71.4%, 76.2%, 74.5%, 61.5%, and 67.0% respectively. The overall prevalence of wound infection was 70.1%. In all the years studied, out-patients had a higher prevalence of wound infection, but this was significant in 2007, 2009, and 2010 only. Staphylococcus aureus was the most prevalent pathogen in both in- and out - patients with the exception of 2009 where both Staphylococcus aureus and Pseudomonas aeruginosa had the same prevalence (24.4%) among in - patients. The flouroquinolones were the most potent antimicrobial agents against bacterial isolates from both in - and out -patients. CONCLUSION: Staphylococcus aureus was the most predominant etiologic agent of wound infection among in and out patients. A generally higher resistance pattern was observed among nosocomial bacterial pathogens. Prudent use of antibiotics is recommended. PMID- 24235936 TI - Comparative anti-inflammatory properties of Capsaicin and ethyl-aAcetate extract of Capsicum frutescens linn [Solanaceae] in rats. AB - BACKGROUND: The analgesic effect of capsaicin (the active ingredient in Capsicum frutescens Linn. [Solanaceae]) had been reported in several studies. Current research is being directed at producing analgesics, anti-inflammatory agents with better side effect profile. OBJECTIVES: To investigate if either the ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) or capsaicin (Fluka Biotechnika-CPF) (in addition to the known analgesic properties) has any anti-inflammatory effect comparable to nonsteroidal anti-inflammatory analgesics (NSAIDS). METHODS: The effects of ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) and capsaicin (Fluka Biotechnika-CPF) was examined on rat hind paw. Inflammation was induced in the rat's hind paw by subplantar injections of fresh egg albumin (0.5 ml/kg). Diclofenac (100 mg/kg) was used as the reference anti-inflammatory agent for comparison, while distilled water was used as the placebo. The leucocytes count, corticosterone and C - reactive protein (CRP) levels were measured as biomarkers of inflammation. Data obtained were pooled and analysed using repeated ANOVA, in a general linear model with the CPSS software. RESULTS: Sub-plantar injections of fresh egg albumin (0.5 ml/kg) produced profound and time-related oedema in the rat hind paw of the 'control' rats. Diclofenac (DIC, 100 mg/kg, i.p.) and reference capsaicin (CPF, 2.5 mg/kg, i.p.) significantly inhibited paw swelling at (p<0.05-0.001) (CI 95%) compared to distilled water-treated 'controls'. While the corticosterone levels were all very low in 7 rats treated with capsaicin, the leucocytes count was within normal range in 9 rats. However, in 16 specimens randomly assigned for CRP levels, there were very high CRP readings, up to a magnitude of 10 times the normal range. CONCLUSIONS: Capsaicin in both forms (CFE and CPF) produced anti-inflammatory effects that were comparable to diclofenac in the experimental rat model at p<0.05. It may be concluded that capsaicin has both analgesic and anti inflammatory properties. PMID- 24235937 TI - The outcome of non-carbapenem-based empirical antibacterial therapy and VRE colonisation in patients with hematological malignancies. AB - BACKGROUND: Febrile neutropenia (FN) is generally a complication of cancer chemotherapy. OBJECTIVES: We retrospectively evaluated the febrile neutropenia episodes and their outcomes with respect to modification rates of non-carbapenem based empirical antibacterial therapy and vancomycin-resistant enterococcus (VRE) colonisation that caused to VRE bacteremia in patients with hematological malignancies. METHODS: All consecutive patients, who were older than 14 years of age and developed febrile neutropenia episodes due to hematological malignancies from September 2010 to November 2011 at the hematology department were included into the study. RESULTS: In total, 86 consecutive neutropenic patients and their 151 febrile episodes were evaluated. The mean MASCC prognostic index score was 18,72 +/- 9,43. Among 86 patients, 28 patients experienced a total of 30 bacteremia episodes of bacterial origin. Modification rates of both, empirical monotherapy and combination therapies, were found similar, statistically (P = 0,840). CONCLUSIONS: Our results suggest that initiating of non-carbapenem based therapy does not provide high response rates in the treatment of febrile neutropenia attacks. Furthermore, non-carbapenem-based empirical therapy provides benefit in regard to cost-effectiveness and antimicrobial stewardship when local antibiotic resistance patterns of gram-negative bacteria are considered. Patients who are colonized with VRE are more likely to develop bacteremia with VRE strains as a result of invasive procedures and severe damage of mucosal barriers observed in this group of patients. PMID- 24235938 TI - Evaluation and comparison of in-vitro dissolution profiles for different brands of amoxicillin capsules. AB - BACKGROUND: Amoxicillin is an oral semi-synthetic, beta-lactam antibiotic used to treat bacterial infections caused by susceptible micro organisms. It is usually prepared in capsule, tablet and powder for oral suspension form. Solid dosage forms for oral administration pose bioavailability problems related to the absorption process The World Health Organization (WHO) has promoted the use of generic brands in order to make the cost of medicines affordable. Generic substitution could be considered when a generic copy of a reference drug contains identical amounts of the same active ingredient in the same dose formulation and route of administration. However, the presences of generic products those are not interchangeable with that of the innovator and/or with each others have been reported. OBJECTIVES: To evaluate and compare the in-vitro dissolution profiles of different generic brands of amoxicillin capsules with the innovator that are available in Ethiopian market. METHODS: Dissolution profiles for nine brands of amoxicillin capsules contained amoxicillin 500 mg which are available in Ethiopian market were determined using a method from the United States Pharmacopoeia (USP, 2009). The obtained dissolution profile data of the eight brands were evaluated and compared with the innovator brand (AmoxilTM) using two different statistical methods: the fit factors (f1 & f2) and the dissolution efficiency (D.E.) model. Most generic brands of amoxicillin capsules (62.5% of the tested brands) are not interchangeable with the innovator brand. RESULTS: The calculated f1 factor for Brand A and Brand G are 10.1 and 1.1 respectively. However, for the rest six brands the f1 factors are greater than 15. The f2 factor for Brand G is 74.1 and for Brand A is 48.5 which is near to 50. Similarly, the f2 factors for the six brands are less than 50 which support the result of the f1 factors for the dissimilarity of these brands with the innovator brand. The mean dissolution efficiencies as well as the 95% confidence intervals are within +/-10% only for two brands, Brand F and Brand G. CONCLUSIONS: Most generic brands of amoxicillin capsules (62.5%) are not interchangeable with the innovator brand (AmoxilTM). PMID- 24235939 TI - Correlates of diarrhoea among children below the age of 5 years in Sudan. AB - BACKGROUND: The Millennium Development Goals recognise child health and survival as an important socio-development issue. OBJECTIVES: To determine the correlates of diarrhoea among children aged below 5 years in north Sudan. METHODS: We conducted secondary data analysis of the Sudan Multiple Cluster Indicators Survey II. RESULTS: Altogether, 23,295 children were included in the survey. Half (50.0%) of the children were males, and 22.5% of them were of age less than one year. Boys were 3% (p=0.044) more likely to have diarrhoea compared to girls. Compared with the oldest age group (48-59 months), children less than 6 months of age and those aged 36-47 months had 25% and 18% lower prevalence of diarrhoea, respectively, while children aged 6-24 months and those aged 24-35 months had 1.5 fold and 1.17 fold higher prevalence of diarrhoea. Children in urban areas were 6% more likely to have diarrhoea. Children from households with 1 or 2 people per room were 8% less likely to have diarrhoea compared to children from households with more than 3 people per room. CONCLUSIONS: Diarrhoea was associated with child's age, gender, and social status. Our findings provide a useful baseline for interventions and comparisons with future studies. PMID- 24235940 TI - Sonographic biometry of spleen among school age children in Nsukka, Southeast, Nigeria. AB - BACKGROUND: Normative value of spleen size among school age children is important for objective assessment of the spleen. OBJECTIVES: This study was aimed at determining sonographically the normal limits of the spleen size according to age, sex, and somatometric parameters among school age children. METHODS: A cross sectional study was done on 947 apparently healthy subjects (496 boys and 451 girls) aged 6 - 17 years. The subjects were recruited from some primary and secondary schools within Nsukka metropolis and also from out patients in the study centre. A pilot study was done to determine the intra- and inter rater reliability of sonographic measurements of the spleen. The sonographic examination was performed on Shenzhen DP-1100 machine with 3.5 and 5 MHz convex transducers. Spleen sizes were obtained with the subject in a right lateral decubitus position. RESULTS: Measurement of spleen length was reliable while measurement of spleen width was less reliable within and between sonographers. Dimensions of the spleen were not statistically different in boys and girls (p > 0.05). Height correlated best with spleen dimensions. CONCLUSIONS: Normogram of the spleen size with respect to height is important in the determination of some pathology associated with changes in its size. PMID- 24235941 TI - Gynaecological laparoscopy courses in the United Arab Emirates. AB - BACKGROUND: Laparoscopic surgery is important for gynaecological practice and became the method of choice for many gynaecological procedures having advantages over open surgery. OBJECTIVES: To report our modified teaching methods, and evaluation of the gynaecological laparoscopy courses in United Arab Emirates. METHODS: Fifty five participants attended four 3-full day comprehensive hands-on gynaecological laparoscopic skills courses. Non-expensive dry/wet models have been developed for teaching. All participants were evaluated at the end of the course through MCQs and practical laparoscopic exercises. All participants filled out a questionnaire reflecting their opinion on various aspects of the course at its completion. Ethical approval has been received by Research and Ethics Committee of Al-Ain Medical District, Al-Ain, UAE. RESULTS: Fourteen participants had no laparoscopic experience, 35 had experience at level I and six had experience at level II. There was a statistically significant difference of the MCQ mark between the three levels of experience (p = 0.05, Kruskal Wallis test) but not for the practical part, p = 0.9, Kruskal Wallis test). The courses were highly valued having an overall average rating of 3.8 out of 4. CONCLUSION: A multimodality non expensive course for teaching gynaecological laparoscopy was highly successful in United Arab Emirates. Models used may be useful for training gynaecological laparoscopy in developing countries. The long term effects of our courses on clinical practice have yet to be evaluated. PMID- 24235942 TI - Physical after effects and clients satisfaction following colposcopy and cervical biopsy in a Nigerian population. AB - BACKGROUND: Although Nigeria has a high prevalence of cervical cancer, screening services including colposcopy and directed cervical biopsy are not widely available. OBJECTIVES: A prospective study among 111 women who had colposcopy and cervical biopsy following an abnormal Pap smear result at the University of Benin Teaching Hospital in Nigeria. It explored physical after effects experienced and satisfaction of clients after the procedure. RESULTS: The mean age of the population was 49.5+/-8.7 years (range, 30 - 64 years) and majority (64.9%) had tertiary education. Overall, 69 women (62.2%) reported physical effects following the procedure. Common physical effects experienced included spotting blood per vaginam (65.2%), pain (34.8%) and vaginal discharge (17.4%). Spontaneous resolution of symptoms occurred within 48 hours in 90.9% of those who reported physical effects. Clients who experienced physical after effects were significantly older (p=0.002) and had tertiary education (p=0.019). Majority of the women (94.6%) were satisfied with the screening services and more than 97% were willing to accept a repeat procedure. CONCLUSIONS: Although majority of the clients who had colposcopy and cervical biopsy reported they experienced physical side effects, more than 97% were willing to have a repeat procedure. This information can assist colposcopic service providers in counseling clients. PMID- 24235943 TI - Condom use at first and latest sexual events among young people: evidence from a rural and peri-urban setting in Uganda. AB - BACKGROUND: Condom use remains low among young people despite high prevalence of HIV, STIs, and unplanned pregnancy in Uganda. OBJECTIVES: This paper presents patterns of condom use at first and latest sexual events and associated factors. METHODS: The data were obtained from 445 sexually active unmarried people aged 15 24 from one peri-urban and another rural district. Stratified multi-stage cluster sampling technique was applied. Logistic regression was used to identify factors associated with condom use at each of the two sexual events, while multinomial logistic regression was used to establish factors correlated with condom use at both first and last sex. RESULTS: Factors associated with condom use at each event were residence in the peri-urban district and higher education attainment. Factors correlated with condom use at both first and last sex were residence in peri-urban district (p<0.001) and being in school (p<0.01). Alcohol consumption and age at first sex were only significant at one event. CONCLUSIONS: Some factors that influence condom use at first sex are different from those that affect condom use at latest sexual event. Prevention programmes against STIs, HIV and unplanned pregnancies among young people focus more on rural areas and those with minimal or no education. PMID- 24235944 TI - Perception and practice of contraception among male soldiers in Sobi barracks, Ilorin, Nigeria. AB - BACKGROUND: There is a popular belief among the general population that Nigerian soldiers tend to have large families but this has not been substantiated with evidence-based research. The Nigerian military health authority implements female targetted contraception strategies, with less focus on their husbands; who are the dominant fertility determinants. OBJECTIVE: To determine the perception and practice of contraception among male soldiers of Sobi Cantonment, Ilorin, Nigeria, with a view to instituting male-targeted contraceptive/family planning strategies. METHODOLOGY: A cross-sectional survey of 334 male soldiers using multistage sampling technique and pre-tested interviewer administered questionnaires. RESULTS: The respondents' approval of contraception (73.6%) and willingness to discuss it with their spouses/partners (71.6%) were high. Fear of wives/partner's sexual promiscuity (55.7%), cultural and religious beliefs (43.2%), fear of the side effects of contraceptives (29.5%) and the desire for more children (21.6%) were reported reasons for the non-approval of contraception. The prevalence of contraceptive use among the respondents was low (12.3%). There was a significant relationship between the respondents' educational level and contraceptive use (p< 0.05). CONCLUSION: The study revealed a high approval and willingness to discuss contraception with their spouses/partners but low contraceptive use. PMID- 24235945 TI - Cost effectiveness of facility and home based HIV voluntary counseling and testing strategies in rural Uganda. AB - BACKGROUND: In Uganda, the main stay for provision of human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) has been at health facilities. Home based VCT on the other hand, was initiated in the country to improve service coverage. OBJECTIVE: To evaluate the cost effectiveness of facility- and home based HIV VCT strategies in rural southwestern Uganda. METHODS: Data on costs and effectiveness of facility- and home-based HIV VCT intervention strategies was collected in two sub-Counties in rural southwestern Uganda. Costing was performed using the ingredients approach. Effectiveness was measured as the number of HIV sero-positive clients identified. Incremental Cost-Effectiveness Ratios (ICERs) were calculated from the provider perspective. RESULTS: The cost per client tested were US$6.4 for facility based VCT and US$5.0 for home based VCT. The corresponding costs per positive case identified were US$86.5 and US$54.7 respectively. The incremental cost to providers per additional positive case identified by facility based VCT was US$3.5. CONCLUSION: Home based VCT was the least costly strategy per client tested and was also cost effective in identifying HIV sero-positive clients in rural areas. This strategy should therefore be promoted to improve service coverage and thereby facilitate early and extensive detection of clients eligible for treatment. PMID- 24235946 TI - Association of anti-Chlamydia antibodies with ectopic pregnancy in Benin city, Nigeria: a case-control study. AB - BACKGROUND: Ectopic pregnancy remains a major public health problem especially in many developing countries where it is a significant contributor to pregnancy related morbidity and mortality. OBJECTIVE: To determine the association between prior Chlamydia trachomatis infection and the risk of ectopic pregnancy. METHODS: A case-control study from two tertiary health care facilities in Benin City, Nigeria. Ninety eight women with ectopic pregnancy (cases) and another 98 women with uncomplicated intrauterine pregnancy (controls) matched for age, were interviewed using a semi-structured questionnaire and evaluated for serological evidence of prior Chlamydia trachomatis infection. RESULTS: The antibody titres in cases (48%) were significantly higher than in controls (16.3%) (p<0.001). However, the association between Chlamydia antibodies and ectopic pregnancy was attenuated when the effects of indicators of previous pelvic infections, socio demographic characteristics, contraceptive and sexual history were controlled for. Primary level of education (OR = 6.32; CI, 2.31 - 17.3), three or more lifetime sexual partners (OR = 5.71; CI, 2.39 - 13.65) and prior history of vaginal discharge (OR = 5.00; CI, 2.03 - 12.3) were more likely to be associated with ectopic pregnancy than with the presence of antibodies to Chlamydia trachomatis (OR = 2.82; 95% CI, 1.33 - 5.95). The Population Attributable Risk was 30.9%. CONCLUSION: Chlamydial infections play only a limited role in the pathogenesis of ectopic pregnancy. PMID- 24235947 TI - Association between history of abdominopelvic surgery and tubal pathology. AB - BACKGROUND: Pelvic infection, unsafe abortion and previous laparatomy are risk factors for tubal infertility among Nigerian women. Reports on the relationship between these factors and tubal pathology seen on hysterosalpingography (HSG) from our environment have been few. OBJECTIVE: To assess the prevalence of tubal occlusions among patients referred for HSG and examine the association between previous history of abdominopelvic surgery (including dilatation and curettage for abortion) and tubal occlusion. METHODS: We studied one hundred and thirty women referred to the Radiology department for HSG because of infertility. HSG was performed during the early proliferative phase of the menstrual cycle. Information about type and duration of infertility, history of abdomino -pelvic surgery and history suggestive of previous pelvic infection, were obtained from the patients. The data obtained were analyzed using SPSS version 11. Test of association using the chi-square test was done where appropriate and differences were considered at p= 0.05. RESULTS: Sixty one women had bilaterally patent tubes; tubal pathology was seen in sixty nine women. Significant association exits between tubal pathology and history of pelvic surgery p=0.01, pelvic infection p=0.02 and duration of infertility p=0.04. CONCLUSION: Previous surgery especially dilation and curettage, PID duration and type of infertility are associated with tubal pathology among Nigerian women. Creative methods of lowering the cost of diagnosis and management of tubal occlusion need to be instituted. PMID- 24235948 TI - Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias. AB - BACKGROUND: Recurrent pregnancy loss (RPL) which is generally known as >3 consecutive pregnancy losses before 20 weeks' gestation is seen in 0.5-2% of women. OBJECTIVE: To evaluate the association of parental and fetal chromosomal abnormalities with recurrent pregnancy loss in our area and to analyze the frequency of three types of hereditary thrombophilia's; (MTHFR C677T polymorphisms, FV Leiden G1691A mutation and Prothrombin (factor II) G20210A mutation) in these female patients. METHODS: The present case-control retrospective study was performed between February 2007 and December 2011 on 495 couples, who had two or more consecutive pregnancy losses before 20 weeks' gestation. We used conventional cytogenetic analysis and polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which (92.9%) were structural abnormalities. All of the structural abnormalities were balanced chromosomal translocations. Chromosomal analysis performed from the abortion materials detected a major chromosomal abnormality in 31.9% of the cases. The most frequently observed alteration in the hereditary thrombophilia genes was heterozygote mutation for the MTHFR C677T polymorphisms (n=55). CONCLUSION: Balanced translocations are the most commonly detected chromosomal abnormalities in couples being evaluated for recurrent pregnancy loss and these patients are the best candidates for offering prenatal genetic diagnosis by the help of which there is a possibility of obtaining a better reproductive outcome. PMID- 24235949 TI - Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria. AB - BACKGROUND: Uterine myomas co-existing with pregnancy could cause obstetric complications. OBJECTIVES: To assess sonographically the frequency of occurrence and effect of uterine myomas co-existing with pregnancy. METHODS: A longitudinal study was conducted during a period of 23 months. A convenience sample of 816 consecutive consenting pregnant women who met the inclusion criteria was evaluated during routine prenatal ultrasound scan. The women were referred for prenatal sonography. One hundred of the subjects who had myoma co-existing with pregnancy and another 100 subjects without myoma were selected for follow-up. These groups were followed up till delivery and obstetric complications and outcomes were documented. Any changes in size and growth rate of myoma were documented. RESULTS: Subjects with myoma co-existing with pregnancy were 12.3%. This was commoner with increasing maternal age. An increase was observed in myoma mean size from 60mm to 63mm from the 1(st) scan sequence to the 2(nd) scan sequence and a reduction from 63mm to 59mm in the 3(rd) scan sequence. Myoma growth rate was 0.667mm per week. Myomas in pregnancy especially large ones caused more complications during delivery when compared to pregnancies without myomas. CONCLUSION: Routine sonography is important in pregnancy management of uterine myomas co-existing with pregnancy. PMID- 24235950 TI - Commonly cited incentives in the community implementation of the emergency maternal and newborn care study in western Kenya. AB - BACKGROUND: Mortality of mothers and newborns is an important public health problem in low-income countries. In the rural setting, implementation of community based education and mobilization are strategies that have sought to reduce these mortalities. Frequently such approaches rely on volunteers within each community. OBJECTIVE: To assess the perceptions of the community volunteers in rural Kenya as they implemented the EmONC program and to identify the incentives that could result in their sustained engagement in the project. METHOD: A community-based cross sectional survey was administered to all volunteers involved in the study. Data were collected using a self-administered supervision tool from all the 881 volunteers. RESULTS: 881 surveys were completed. 769 respondents requested some form of incentive; 200 (26%) were for monetary allowance, 149 (19.4%) were for a bicycle to be used for transportation, 119 (15.5%) were for uniforms for identification, 88 (11.4%) were for provision of training materials, 81(10.5%) were for training in Home based Life Saving Skills (HBLSS), 57(7.4%) were for provision of first AID kits, and 39(5%) were for provision of training more facilitators, 36(4.7%) were for provision of free medication. CONCLUSION: Monetary allowances, improved transportation and some sort of identification are the main incentives cited by the respondents in this context. PMID- 24235951 TI - Peripartum hysterectomy: two years experience at Nelson Mandela Academic hospital, Mthatha, Eastern Cape South Africa. AB - BACKGROUND: Obstetric haemorrhage is the leading direct cause of maternal mortality in South Africa. OBJECTIVE: To determine the incidence, indications, associations and maternal outcomes of emergency peripartum hysterectomies. METHODS: A descriptive and retrospective analysis of patients who had peripartum hysterectomy between 1(st) February 2007 and 31(st) January 2009 in Nelson Mandela Academic Hospital at Mthatha city. RESULTS: The incidence of 0.95% of peripartum hysterectomies (n=63 or 9.5/1000 births) increased with the increasing maternal age from 0.121% at age of less than 20 years to 0.5% at age more or equal to 30 years. Similarly the incidence increased with parity from 0.332% for Primiparity to 0.468% at parity of four or more. The indications for the operation were uterine atony 19/63 (30.2%), secondary haemorrhage/puerperal sepsis 17/63 (27%) and ruptured uterus 16/63 (23.4%). The main intra operative complication was haemorrhage 13/63 (20.6%). Repeat laparotomy was done in 10/63 (15%) of patients due to haemorrhage. Admission to intensive care unit was 25/63 (39.7%). The case specific mortality rate was of 19 % (n=12). The main causes of death were hypovolaemic shock and septicemia. CONCLUSION: The incidence of peripartum hysterectomies was high and was associated with ruptured uterus and puerperal sepsis which are preventable. PMID- 24235952 TI - Antiemetic effects of dexamethasone and ondansetron combination during cesarean sections under spinal anaesthesia. AB - BACKGROUND: Nausea and vomiting are frequently seen in patients undergoing cesarean section (CS) under regional anesthesia. We aimed to compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the use of each agent alone to decrease the incidence of post-delivery intraoperative nausea and vomiting (IONV) during CS under spinal anesthesia. OBJECTIVE: To compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the single use of each agent to decrease the incidence of postdelivery IONV during CS under spinal anesthesia. METHODS: A randomized, prospective, double blind study was performed on 90 patients undergoing planned CS under spinal anesthesia. Patients received 4mg ondansetron in Group O, 8mg dexamethasone in GroupD, 4mg ondansetron+8mg dexamethasone in Group OD intravenously within 1-2 minutes after the umbilical cord was clamped. Frequency of postdelivery IONV episodes was recorded. RESULTS: A total of 86 eligible patients were included in the study. There were 29 patients in Group O, 29 patients in Group D and 28 patients in Group OD. There were no statistically significant difference between the groups in terms of baseline characteristics and intraoperative managements. Frequency of intraoperative nausea, retching and vomiting experiences were similar between the groups (p>0.05). CONCLUSION: Single dose 4mg ondansetron, 8mg dexamethasone, or combined use of 8mg dexamethasone+4mg ondansetron, given intravenously is all effective agents for the control of postdelivery IONV. Combined use of dexamethasone and ondansetron for the same indication does not seem to increase the antiemetic efficacy. PMID- 24235953 TI - The effect of unilateral vasectomy on testosterone and testicular parameters in the adult male African giant rat (Cricetomys gambianus). AB - BACKGROUND: The effects of vasectomy on spermatogenesis and reproductive parameters are recognized to be specie-dependent with marked differences in levels of perturbations observed. OBJECTIVES: To assess the impact of unilateral vasectomy on testosterone level and other testicular parameters in the male African giant rat (AGR) (Cricetomys gambianus). METHODS: Sixteen adult male AGRs weighing 500-1300 g were recruited for the experiment. Animals were randomly divided into three experimental groups (1-3) and one control (sham operated) group with four rats per group. Experimental vasectomy was done by carefully ligating the vas deferens of the right testis of all the experimental groups (1, 2, and 3) and animals were allowed either 8, 6 and 2 weeks respectively before sacrifice. Sham-operated animals served as the control. Blood samples were collected and assayed for testosterone while testicular tissue was further processed for seminal fluid and histo-pathological analyses. RESULTS: Spermatogenic parameters indicate a pattern of decline in sperm count and motility between the experimental groups and the control and azoospermia in the eight-week group. Histological alterations were marked by atrophy of seminiferous tubules which was proportional to the duration of vasectomy. Serum testosterone levels were significantly reduced at eight weeks. There was no statistically significant difference between sperm counts of right and left testes except for group 3. Results suggest that unilateral vasectomy of the AGR may have negative impact on the contralateral testis in the male African giant rat. CONCLUSION: These preliminary results reveal that unilateral vasectomy in the AGR may result in perturbations of the histo-architecture of the testes with possible decline in function. PMID- 24235954 TI - Alcohol consumption and cigarette smoking pattern among brothel-based female sex workers in two local government areas in Lagos state, Nigeria. AB - BACKGROUND: Alcohol and tobacco use are known risk factors for non communicable diseases especially among women. Brothel based female sex workers may be at increased risk of exposure to these two substances. OBJECTIVE: To assess the pattern of alcohol and tobacco use among female sex workers in two selected local government areas in Lagos state, Nigeria. METHODS: A cross-sectional descriptive study was carried out among 323 brothel-based female sex workers in 39 consenting brothels. Data was collected by trained interviewers using a pretested structured questionnaire. RESULTS: Majority (67.8%) were current drinkers with 89.5% of these having their most recent drink less than a week ago. Most of them (89%) consumed more than the reference limits for alcohol use among women. Up to 20.7% were current smokers with (92.5%) having their most recent cigarette less than a week ago. More than a third (37.4%) were heavy smokers while 19% were dual users. Current drinking was associated with current smoking. Smokers consumed significantly more units of alcohol than non-smokers. CONCLUSION: The prevalence of harmful alcohol use and cigarette smoking are very high among this group of female sex workers. Programs that address the use of these substances should be made available for these women. PMID- 24235955 TI - Living with parents and risky sexual behaviors among preparatory school students in Jimma zone, South west Ethiopia. AB - BACKGROUND: Risky sexual behavior is any behavior that increases the probability of negative consequences associated with sexual contact. Family environment, peer influence, community factors and school attachment seem an important factor affecting sexual risk behavior and decision of in-school youths. OBJECTIVE: To assess sexual risk behaviors and associated factors among students living with parents in Jimma zone preparatory schools. METHODS: A cross sectional study designs both qualitative and quantitative approaches was conducted in 5 randomly selected preparatory schools. A total of 273 students were randomly selected. Multiple logistic regressions were performed to identify the independent predictor of risk sexual behavior. RESULT: One hundred fiten (42.1%) students had sexual risk behavior. Thirty six (30.8%) student's reports they had two or more sexual partners in their lifetime. Out of 117 students, 13 (11.2%) students used condom always. One hundred one (37%) students were consumed alcohol. Higher likelihood of risky sexual behavior significantly associated with higher levels of alcohol consumption and low frequency of religious visit. CONCLUSION: Alcohol consumption and religious visit were the major predictors of risky sexual behaviors. Therefore, Behavior change communication should consider family environment and other factors which predict risk sexual behaviors. PMID- 24235956 TI - Hand hygiene practices among community Health Officers in Rivers State, Nigeria. AB - BACKGROUND: Health care associated infections are most commonly transmitted by the hands of Health care workers and other hospital personnel. OBJECTIVE: To investigate compliance with hand hygiene guidelines and methods of hand hygiene practice among community health officers in Rivers State Nigeria. METHODS: Self administered questionnaires were distributed to 68 community health officers. The questionnaires consisted of 19 items which contained information on bio demographic characteristics and hand hygiene practices. Data were analysed using SPSS-16 statistical software. Proportions were compared using Chi- square test and 'p' value less than 0.05 was considered statistically significant. RESULTS: The response rate was 97.1%. There were 11 (16.7%) males and 55 (83.3%) females with a male to female ratio of 1: 5. The age of the participants ranged from 28 56 years with a mean age of 39.7+/-6.7. Washing of hands before and after contact with patient was 60.1% and 97% respectively. The difference was significant (p<0.01). Allergy to gloves was 15.2%. About three-quarter (77.3%) of the workers used soap and water to wash the hands when soiled or visibly contaminated. None of the workers used alcohol hand rub. CONCLUSION: Though there was improved compliance to hand hygiene guidelines, this still fall short of acceptable standards. The provision and promotion of the proper use of alcohol-based hand rub may further improve compliance with hand hygiene by reducing the time required to perform it and the convenience of the method. PMID- 24235957 TI - Design and implementation of participatory hygiene and sanitation transformation (PHAST) as a strategy to control soil-transmitted helminth infections in Luweero, Uganda. AB - BACKGROUND: The study is a continuation of a research carried out in Luweero district in Uganda1. It investigated whether PHAST was a suitable tool for reducing transmission of soil transmitted helminths. PHAST means Participatory Hygiene and Sanitation Transformation; a participatory approach that uses visual tools to stimulate the participation of people in promotion of improved hygiene and sanitation. OBJECTIVE: To assess the effect of PHAST on intestinal helminth transmission in children under five years. METHODS: Three phases namely; (1) Baseline survey (2) PHAST intervention (3) Follow up were conducted. During Phase 1, the subjects' stool samples were examined for presence of helminthic ova and questionnaires administered. In Phase 2, PHAST was conducted only in experimental villages. All subjects in the experimental and control villages were treated thrice with Albendazole. During Phase 3, all steps of Phase 1 were repeated. RESULTS: There was an overall reduction in the prevalence of children infected with helminths after PHAST intervention. Also, comparison of pre-intervention and post-intervention multivariate results indicates that the likelihood of children getting infected with helminths reduced in most of the experimented variables. CONCLUSION: Health stakeholders should utilize PHAST approach to sensitize communities on the importance of hygiene to curb soil-transmitted helminth infections. PMID- 24235958 TI - Disseminated Histoplasmosis in a 13-year-old girl: a case report. AB - BACKGROUND: Disseminated histoplasmosis is a rare fungal infection and most documented cases are in immune-compromised individuals such as those with acquired immuno-deficiency syndrome. OBJECTIVE: To describe a case of disseminated histoplasmosis in an adolescent girl. METHOD: We report a case of disseminated histoplasmosis in a 13-year-old adolescent girl. She was admitted for 16 days because of neck masses of 3 years duration, generalized body swelling of 3 months and reduction in urinary output of 2 months. She tested negative for human immunodeficiency virus antibodies. RESULT: An autopsy was performed because a definitive diagnosis could not be made while the patient was still alive. The autopsy revealed central caseating areas in the lymph nodes and membranoproliferative glomerulonephritis. The periodic acid-Schiff staining technique for tissues showed viable yeast cells suggestive of histoplasmosis. Zeihl-Neelsen's staining for mycobacteria tuberculosis was negative. CONCLUSION: Undiagnosed case of disseminated histoplasmosis while the patient was alive is being reported in a 13-year-old girl. Disseminated histoplasmosis should be considered as a differential diagnosis of childhood chronic infections and malignancies as in Nigeria. PMID- 24235960 TI - Death and cadavers: knowledge, skills and attitudes will have to change. PMID- 24235959 TI - Tuberculosis diagnosis in resource-limited settings: Clinical use of GeneXpert in the diagnosis of smear-negative PTB: a case report. AB - BACKGROUND: The Xpert MTB/RIF test (GeneXpert) has recently been endorsed for use in resource-limited settings for the diagnosis of tuberculosis and drug resistant tuberculosis. In resource-limited settings, GeneXpert has been used predominantly for research and there is little experience with its use in day-to-day management of patients. CASE SUMMARY: We describe a case of a 46 year old HIV-infected male with smear-negative pulmonary tuberculosis, who had several visits to various lower level health centres and two admissions in a tertiary care hospital; however, the diagnosis of tuberculosis was only made several months later on GeneXpert testing that was performed under a research project. CONCLUSION: GeneXpert facilitated identification of tuberculosis in an HIV positive patient in whom the diagnosis had been delayed when more widely available tests were used. Operational and cost-effectiveness studies are needed to provide evidence to policy makers in order to improve access to GeneXpert. PMID- 24235961 TI - How to change West-African minds in order to increase general acceptation of autopsies? PMID- 24235962 TI - Response to: acute organo-phosphorus pesticide poisoning in North Karnataka, India: oxidative damage, haemoglobin level and total leukocyte. PMID- 24235963 TI - Response to: causes of visual disability among Central Africans with diabetes mellitus. PMID- 24235964 TI - MRI findings in people with epilepsy and nodding syndrome in an area endemic for onchocerciasis: an observational study. AB - BACKGROUND: Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome. OBJECTIVE: To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection. METHODS: In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF. RESULTS: The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher's Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher's Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients. CONCLUSION: The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention. PMID- 24235965 TI - Nodding syndrome, infections and sexuality. PMID- 24235966 TI - Gastric Intestinal Metaplasia in an Underserved Population in the USA: Prevalence, Epidemiologic and Clinical Features. AB - Gastric intestinal metaplasia is an important stage in the development of gastric cancer. Limited data is available regarding the prevalence of gastric intestinal metaplasia in the United States. We conducted a retrospective review of esophagogastroduodenoscopies performed in our endoscopy unit between the months of April and October 2010 to evaluate the prevalence and the epidemiologic and endoscopic features of gastric intestinal metaplasia in an underserved population in the United States. PMID- 24235967 TI - H-ras oncogene expression and angiogenesis in experimental liver cirrhosis. AB - Background. Proto-oncogenes, particularly ras, may not only affect cell proliferation but also contribute to angiogenesis by influencing both proangiogenic and antiangiogenic mediators. The aim of this study was to investigate whether any relationship exists between ras expression and angiogenesis during diethylnitrosamine- (DEN-) induced experimental liver fibrosis. Materials and Methods. Liver cirrhosis was induced in rats by intraperitoneal injections of DEN. The animals were sacrificed 2 weeks after the last administrations and a hepatectomy was performed. Masson's trichrome staining was used in the evaluation of the extent of liver fibrosis. The vascular density in portal and periportal areas was assessed by determining the count of CD34 labeled vessel sections. For quantitative evaluation of H-ras expression, in each section positive and negative cells were counted. Results. In fibrotic group H ras expression was higher than that in nonfibrotic group and was more widespread in cirrhotic livers. Friedman's test showed that there was a significant correlation between H-ras expression and VD (P < 0.01). Conclusion. The results of this descriptive study reveal that H-ras expression gradually increases according to the severity of fibrosis and strongly correlates with angiogenesis. PMID- 24235968 TI - Ten-Day versus 14-Day Levofloxacin-Containing Triple Therapy for Second-Line Anti Helicobacter pylori Eradication in Taiwan. AB - Second-line Helicobacter pylori (H. pylori) eradication with fluoroquinolone containing triple therapy is one of the recommended treatment options, but neither 7-day nor 10-day regimens provide >90% success rates. The current retrospective study aimed to clarify the effects of 10-day and 14-day levofloxacin-containing triple therapies for second-line H. pylori eradication in a Taiwanese cohort and to evaluate the potential clinical factors influencing eradication. A total of 200 patients who failed H. pylori eradication using the standard triple therapy were prescribed with either a 10-day (EAL-10) or a 14-day (EAL-14) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Follow up studies to assess treatment response were carried out 8 weeks later. Eradication rates attained by EAL-10 and EAL-14 were 75.6%; 95% CI = 63.9-85.3% and 92.5%; 95% CI = 84.5-98.1%, P = 0.002 in the per protocol analysis and 68%; 95% CI = 56.6-78.5% and 86%; 95% CI = 76.8-93.4%, P = 0.002 in the intention-to treat analysis. The duration of H. pylori therapy is the independent risk factor of H. pylori eradication (P = 0.003). In conclusion, 14-day levofloxacin containing triple therapy can provide a >90% H. pylori eradication rate, but 10 day treatment duration may be suboptimal. The longer duration of H. pylori therapy (14 days) is the independent risk factor. PMID- 24235969 TI - A comparison of calcium hydroxyapatite and dextranomer/hyaluronic Acid for the endoscopic treatment of vesicoureteral reflux. AB - Purpose. Minimal data exists comparing dextranomer/hyaluronic acid (Dx/HA) and calcium hydroxyapatite (CaHA) for the endoscopic treatment of VUR in the hands of a single user. Materials and Methods. We reviewed our consecutive single-user case series of 27 children (42 ureters) receiving endoscopic treatment with CaHA and 21 children (33 ureters) who received Dx/HA injection. Children receiving CaHA injections were divided into two groups of 13 and 14 patients (Coaptite I and II) to assess the learning curve effects. Postoperatively, RBUS and VCUG were performed. Multiple regression analysis was performed to assess statistical significance of success rates. Results. The total CaHA group had a per-ureter success rate (Grade 0) of 52% after one injection. When separated into two cohorts, the single injection per-ureter success rates were 43% for Coaptite I and 62% for Coaptite II. In contrast, the Dx/HA series had a single injection per ureter success rate (Grade 0) of 78%. Conclusions. Our consecutive case experience shows improved results for Dx/HA compared to CaHA, though the learning curve effects and evolution of injection technique likely played a role in the improved outcomes in the Dx/HA cohort. A randomized controlled multicenter trial would provide the most accurate data comparing these two agents. PMID- 24235970 TI - Randomized controlled trial to compare the safety and efficacy of tamsulosin, solifenacin, and combination of both in treatment of double-j stent-related lower urinary symptoms. AB - Purpose. We evaluated the effectiveness and safety of tamsulosin, solifenacin, and combination of both in reducing double-J stent-related lower urinary symptoms. Materials and Methods. A total of 338 patients with double-J ureteral stenting were randomly divided, postoperatively, into 4 groups. In group I (n = 84), no treatment was given (control group), group II (n = 85) received tamsulosin 0.4 mg daily, group III (n = 84) received solifenacin 10 mg daily, and group IV (n = 85) received a combination of both medications. Before insertion and 2 weeks after, all patients completed the International Prostate Symptom Score (IPSS), quality of life component of the IPSS (IPSS/Qol), Overactive Bladder Questionnaire (OAB-q), and Visual Analogue Pain Scale (VAPS) questionnaire. Results. The demographics and preoperative questionnaires scores of all groups were comparable. There were statistically significant differences in all scores in favour of groups II, III, and IV as compared to control group (P value < 0.005). Group IV showed statistically significant differences in total IPSS, QoL score, and OAB-q score as compared to groups II and III (P value < 0.001). Conclusions. Combined therapy of tamsulosin and solifenacin significantly alleviated lower urinary symptoms associated with double-J stents as compared to either medication alone. PMID- 24235971 TI - Supraventricular arrhythmias after thoracotomy: is there a role for autonomic imbalance? AB - Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilization. PMID- 24235972 TI - The diagnostic value of transcription factors T-bet/GATA3 ratio in predicting antibody-mediated rejection. AB - BACKGROUND: Previous data showed that the predominance of intraglomerular T-bet or GATA3 is correlated with different mechanisms of rejection, suggesting that the ratio of T-bet/GATA3 might be used to distinguish antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR). METHODS: We compared the intraglomerular T-bet/GATA3 ratio in ABMR and TCMR. The intragraft expression of T-bet and GATA3 was studied via immunohistochemistry. The correlation of the diagnosis of AMR with the ratio of T-bet/GATA3 was examined. RESULTS: Both intraglomerular T-bet- and GATA3-expressing cells were increased during acute rejection. T-bet/GATA3>1 was strongly correlated with ABMR (93.3% versus 18.2%). The incidence of positive HLA-I/II antibodies and glomerulitis is significantly higher in T-bet/GATA3>1 group (P < 0.001, 0.013, resp.). The scores of peritubular capillary inflammation and glomerulitis were also higher in T bet/GATA3>1 group (P = 0.052, P < 0.001, resp.). Nevertheless, T-bet/GATA3>1 is also correlated with C4d-negative ABMR and resistance to steroid treatment. Compared with C4d deposition, T-bet/GATA3>1 had a slight lower (90% versus 100%) specificity but a much higher (87.5% versus 68.8%) sensitivity. CONCLUSION: Our data suggested that intraglomerular predominance of T-bet over GATA3 might be used as diagnosis maker of ABMR in addition to C4d, especially in C4d-negative cases. PMID- 24235973 TI - Chronic deep brain stimulation of the hypothalamic nucleus in wistar rats alters circulatory levels of corticosterone and proinflammatory cytokines. AB - Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-alpha (120%; P < 0.01) and IFN-gamma (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1beta (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID- 24235974 TI - IMAGES OF BLACK AMERICANS: Then, "Them," and Now, "Obama!" AB - Images of Black Americans are becoming remarkably diverse, enabling Barack Obama to defy simple-minded stereotypes and succeed. Understood through the Stereotype Content Model's demonstrably fundamental trait dimensions of perceived warmth and competence, images of Black Americans show three relevant patterns. Stereotyping by omission allows non-Blacks to accentuate the positive, excluding any lingering negativity but implying it by its absence; specifically, describing Black Americans as gregarious and passionate suggests warmth but ignores competence and implies its lack. Obama's credentials prevented him from being cast as incompetent, though the experience debate continued. His legendary calm and passionate charisma saved him on the warmth dimension. Social class subtypes for Black Americans differentiate dramatically between low-income Blacks and Black professionals, among both non-Black and Black samples. Obama clearly fit the moderately warm, highly competent Black-professional subtype. Finally, the campaign's events (and nonevents) allowed voter habituation to overcome non Blacks' automatic emotional vigilance to Black Americans. PMID- 24235975 TI - Difficulties sleeping: a natural part of growing older? PMID- 24235976 TI - Electron Ionization-Induced Release of Coded Isotopic Reporter Ions in an m/z Zone of Minimal Interference for Quantifiable, Multiplexed GC-MS Analyses. AB - We describe an isotope coding strategy that enables simultaneous GC-MS analysis of multiple samples for substrate identification and quantification. The method relies on direct measurement of isotopic ethyl carbenium ions serving as mass spectral tags in a zone of minimal interference (ZMI) at m/z 31-37. Sample aldehyde and ketone mixtures were reacted with isotopic 2-aminooxyethyl propionates to illustrate the method, which determined the relative abundance of the mixed compounds with an average 95% accuracy. ZMI reporter ion detection also enables chemoselective substrate profiling and absolute quantification, as demonstrated using a biologically derived sample. PMID- 24235977 TI - Single-cell profiling of circulating tumour cells: a great leap forward. PMID- 24235979 TI - Lower-Limb Power cannot be Estimated Accurately from Vertical Jump Tests. AB - The countermovement jump test is often adopted to monitor lower-limb power of an individual. Despite several studies on the validity of this test, there is still a need to determine the minimal difference needed to be confident that a difference in power between two individuals is present or that a true change in the performance of an individual has occurred. In this study, power was measured from ground reaction forces and compared to that obtained from predictive equations for two groups of subjects (67 trained and 20 highly trained individuals). The height of each jump was determined with kinematic techniques. The main outcome is a large discrepancy between power calculated from ground reaction forces and that calculated from predictive equations. For the trained group, the R-square value between power and predicted power was 0.53 and the minimal difference to consider that two individuals were different was 821.7 W. For the highly trained individuals, a much larger R-square value was obtained (0.94). Despite this, the minimal difference to consider that two individuals were different was still large (689.3 W). The large minimal differences obtained raise serious concerns about using countermovement jumps for appraisal and monitoring of lower-limb power of an individual. PMID- 24235978 TI - Detection of Aortic Wall Inclusion Using Regional Pulse Wave Propagation and Velocity In Silico. AB - Monitoring of the regional stiffening of the arterial wall may prove important in the diagnosis of various vascular pathologies. The pulse wave velocity (PWV) along the aortic wall has been shown to be dependent on the wall stiffness and has played a fundamental role in a range of diagnostic methods. Conventional clinical methods involve a global examination of the pulse traveling between two remote sites, e.g. femoral and carotid arteries, to provide an average PWV estimate. However, the majority of vascular diseases entail regional vascular changes and therefore may not be detected by a global PWV estimate. In this paper, a fluid-structure interaction study of straight-geometry aortas was carried out to examine the effects of regional stiffness changes on PWV. Five homogeneous aortas with increasing wall stiffness as well as two aortas with soft and hard inclusions were considered. In each case, spatio-temporal maps of the wall motion were used to analyze the regional pulse wave propagation. On the homogeneous aortas, increasing PWVs were found to increase with the wall moduli (R2 = 0.9988), indicating the reliability of the model to accurately represent the wave propagation. On the inhomogeneous aortas, formation of reflected and standing waves was observed at the site of the hard and soft inclusions, respectively. Neither the hard nor the soft inclusion had a significant effect on the velocity of the traveling pulse beyond the inclusion site, which supported the hypothesis that a global measurement of the average PWV could fail to detect regional abnormalities. PMID- 24235980 TI - Kinematic Variables Evolution During a 200-m Maximum Test in Young Paddlers. AB - The objective of this research was to determine the kinematic variables evolution in a sprint canoeing maximal test over 200 m, comparing women and men kayak paddlers and men canoeists. Speed evolution, cycle frequency, cycle length and cycle index were analysed each 50 m section in fifty-two young paddlers (20 male kayakers, 17 female kayakers and 15 male canoeists; 13-14 years-old). Recordings were taken from a boat which followed each paddler trial in order to measure the variables cited above. Kinematic evolution was similar in the three categories, the speed and cycle index decreased through the test after the first 50 m. Significant differences were observed among most of the sections in speed and the cycle index (p<0.05 and <0.01, respectively). Cycle length remained stable showing the lowest values in the first section when compared with the others (p<0.01). Cycle frequency progressively decreased along the distance. Significant differences were identified in the majority of the sections (p<0.01). Men kayakers attained higher values in all the variables than women kayakers and men canoeists, but only such variables as speed, cycle length and cycle index were observed to be significantly higher (p<0.01). Moreover, lower kinematic values were obtained from men canoeists. The study of the evolution of kinematic variables can provide valuable information for athletes and coaches while planning training sessions and competitions. PMID- 24235981 TI - The development of a repetition-load scheme for the eccentric-only bench press exercise. AB - The purpose of the present study was to develop a repetition-load scheme for the eccentric-only bench press exercise. Nine resistance trained men (age: 21.6 +/- 1.0 years; 1-repetition maximum [RM] bench press: 137.7 +/- 30.4 kg) attended four testing sessions during a four week period. During the first session each subject's 1-RM bench press load utilizing the stretch-shortening cycle was determined. During the remaining sessions they performed eccentric-only repetitions to failure using supra-maximal loads equivalent to 110%, 120% and 130% of their 1-RM value with a constant cadence (30 reps.min(-1)). Force plates and a three dimensional motion analysis system were used during these final three sessions in order to evaluate kinematic and kinetic variables. More repetitions were completed during the 110% 1-RM condition compared to the 130% 1-RM condition (p=0.01). Mean total work (p=0.046) as well as vertical force (p=0.049), vertical work (p=0.017), and vertical power output (p=0.05) were significantly greater during the 130% 1-RM condition compared to the 110% 1-RM condition. A linear function was fitted to the number of repetitions completed under each load condition that allowed the determination of the maximum number of repetitions that could be completed under other supra-maximal loads. This linear function predicted an eccentric-only 1-RM in the bench press with a load equivalent to 164.8% 1-RM, producing a load of 227.0 +/- 50.0 kg. The repetition-load scheme presented here should provide a starting point for researchers to investigate the kinematic, kinetic and metabolic responses to eccentric-only bench press workouts. PMID- 24235982 TI - Body posture stability in ski boots under conditions of unstable supporting surface. AB - THE AUTHORS ATTEMPTED TO DETERMINE WHETHER: (1) there are differences in stability between the conditions of standing in ski boots and barefoot, (2) the type of surface affects stability, and, (3) the level of stability differs between the frontal and sagittal planes. The study included 35 young male recreational skiers aged 20.71 +/-0.63 years. Measurements of stability were taken by means of a Libra seesaw balance board. The conditions of soft surface were created by attaching an inflated cushion to the board. The experiment was carried out on both rigid and soft surface for both movement planes and two different conditions: maintaining the seesaw balance board in the horizontal position and performance of a particular balancing task. All the tests were performed with visual feedback. Restricted ankle joint mobility that results from wearing ski boots caused a reduction of stability in studied subjects, particularly in the sagittal plane. The differences found in the study were likely to be caused by the difficulty the beginners experienced in re-organizing muscular coordination in hip joint strategy and effectively using mechanical support of ski boots that reduces lower limb muscle tone. The use of the soft surface improved stability exhibited by the subjects in the frontal plane without compromising the stability in the sagittal plane. The soft surface might have contributed to a reduction in excessive corrective movements, thus improving stability in studied subjects. The aim of this study was to determine the effect of limitation of foot mobility and disturbances in afferent information from the plantar mechanoreceptors due to wearing ski boots on the level of postural stability in beginner skiers under conditions of the unstable support surface. PMID- 24235983 TI - Postural adaptations in preadolescent karate athletes due to a one week karate training cAMP. AB - The aim of this study was to investigate the effect of an increasing number of training hours of specific high-intensity karate training on postural sway in preadolescent karate athletes. Seventy-four karatekas were randomly assigned to 1 of 2 groups: Karate Group (KG=37): age 10.29+/-1.68 yrs; or Control Group (CG= 37): age 10.06+/-1.77 yrs. The KG performed two sessions per day for 1 week in total, while the CG performed only 3 sessions during the same period. The center of-pressure length (COPL) and velocity (COPV) were recorded under four different experimental conditions: open eyes (EO), closed eyes (EC), open eyes monopodalic left (EOL), open eyes monopodalic right (EOR), pre as well as post training intervention. Post-camp results indicated significant differences between the groups in the COPL p<0.001; an interaction of training type*time in the COPV (p<0.001) and an interaction of training type*time (p=0.020). The KG revealed an improvement in the COPL from pre to post-camp under conditions of EO [-37.26% (p<0.001)], EC [-31.72% (p<0.001)], EOL [-27.27% (p<0.001)], EOR [-21.44% (p<0.001)], while CG revealed small adaptations in conditions of EO (3.16%), EC (0.93%), EOL (-3.03%), EOR (-0.97%). Furthermore, in the KG an improvement in the COPV from pre to post-camp was observed in conditions of EO [-37.92% (p<0.001)], EC [-32.52% (p<0.001)], EOL [-29.11% (p<0.001)], EOR [-21.49% (p<0.001)]. In summary, one-week of high intensity karate training induced a significant improvement in static body balance in preadolescent karate athletes. Karate performance requires high-levels of both static and dynamic balance. Further research dealing with the effect of karate practice on dynamic body balance in young athletes is required. PMID- 24235984 TI - Are various forms of locomotion-speed diverse or unique performance quality? AB - The forward-sprint is considered to be, and is regularly performed as, a unique measure of "on-ground" linear-speed performance. Thus far, no investigation has simultaneously studied different forms of linear-speed or investigated whether different forms of linear-speed should be observed as unique performance quality. The purpose of this study was to determine (I) the achievements (i.e. execution time), and (II) the reliability and inter-relationships between various linear speed performances. The participants were 42 male physical education students with substantial sport-specific backgrounds. We applied a total of six tests: three quadrupedal (supine backward, supine forward, and pronate backward locomotion) and three bipedal-performances (forward sprinting, backward sprinting, lateral shuffling). All of the tests showed appropriate reliability parameters (Cronbach Alpha ranged from 0.91 to 0.97; Inter-Item-R 0.78-0.92; Coefficient-of-Variation 1.3-9.1). The tests used in this study shared between 9% and 50% of the common variance. Our results suggest that different activities require activity-specific tests of linear-speed. This is particularly significant in those sports and activities in which quadrupedal locomotion patterns are highly important (wrestling, physically trained military services, law enforcement, fire and rescue, protective services). PMID- 24235985 TI - A comparison of muscle activity in concentric and counter movement maximum bench press. AB - The purpose of this study was to compare the kinematics and muscle activation patterns of regular free-weight bench press (counter movement) with pure concentric lifts in the ascending phase of a successful one repetition maximum (1 RM) attempt in the bench press. Our aim was to evaluate if diminishing potentiation could be the cause of the sticking region. Since diminishing potentiation cannot occur in pure concentric lifts, the occurrence of a sticking region in this type of muscle actions would support the hypothesis that the sticking region is due to a poor mechanical position. Eleven male participants (age 21.9 +/- 1.7 yrs, body mass 80.7 +/- 10.9 kg, body height 1.79 +/- 0.07 m) conducted 1-RM lifts in counter movement and in pure concentric bench presses in which kinematics and EMG activity were measured. In both conditions, a sticking region occurred. However, the start of the sticking region was different between the two bench presses. In addition, in four of six muscles, the muscle activity was higher in the counter movement bench press compared to the concentric one. Considering the findings of the muscle activity of six muscles during the maximal lifts it was concluded that the diminishing effect of force potentiation, which occurs in the counter movement bench press, in combination with a delayed muscle activation unlikely explains the existence of the sticking region in a 1-RM bench press. Most likely, the sticking region is the result of a poor mechanical force position. PMID- 24235986 TI - Mechanical work and long-distance performance prediction: the influence of allometric scaling. AB - The purpose of this study was to examine the effect of allometric scaling on the relationship between mechanical work and long-distance running performance in recreational runners. Fourteen recreational long-distance runners (male, mean +/- SD - age: 29 +/- 7 years; body mass: 70.0 +/- 10.2 kg; body height: 1.71 +/- 0.07 m; maximal oxygen uptake: VO2max 52.0 +/- 4.9 ml.kg(-1).min(-1)) performed two tests: a continuous incremental test to volitional exhaustion in order to determine VO2max, and a 6-minute running submaximal test at 3.1 m.s(-1), during which segments in the sagittal plane were recorded using a digital camera and the internal (Wint), external (Wext) and total (Wtot) mechanic work, in J.kg(-1).m( 1), was subsequently calculated. The results indicated a significant correlation between mechanical work and performance, however, the strongest correlations were observed when allometric exponents were used (respectively for Wint, Wext and Wtot; non allometric vs. allometric scaling defined by literature (0.75) or determined mathematically (0.49): r = 0.38 vs. r = 0.44 and r = 0.50; r = 0.80 vs. r = 0.83 and r = 0.82; r = 0.70 vs. r = 0.77 and r = 0.78). These results indicate that mechanical work could be used as a predictor of recreational long distance performance and an allometric model may improve this prediction. PMID- 24235987 TI - Potentiation increases peak twitch torque by enhancing rates of torque development and relaxation. AB - The aim of this study was to measure the extent to which potentiation changes in response to an isometric maximal voluntary contraction. Eleven physically active subjects participated in two separate studies. Single stimulus of electrical stimulation of the femoral nerve was used to measure torque at rest in unpotentiated quadriceps muscles (study 1 and 2), and potentiated quadriceps muscles torque in a 10 min period after a 5 s isometric maximal voluntary contraction of the quadriceps muscles (study 1). Additionally, potentiated quadriceps muscles torque was measured every min after a further 10 maximal voluntary contractions repeated every min (study 2). Electrical stimulation repeated several times without previous maximal voluntary contraction showed similar peak twitch torque. Peak twitch torque 4 s after a 5 s maximal voluntary contraction increased by 45+/-13% (study 1) and by 56+/-10% (study 2), the rate of torque development by 53+/-13% and 82+/-29%, and the rate of relaxation by 50+/-17% and 59+/-22%, respectively, but potentiation was lost already two min after a 5 s maximal voluntary contraction. There was a tendency for peak twitch torque to increase for the first five repeated maximal voluntary contractions, suggesting increased potentiation with additional maximal voluntary contractions. Correlations for peak twitch torque vs the rate of torque development and for the rate of relaxation were r(2)= 0.94 and r(2)=0.97. The correlation between peak twitch torque, the rate of torque development and the rate of relaxation suggests that potentiation is due to instantaneous changes in skeletal muscle contractility and relaxation. PMID- 24235988 TI - Estimating the energy costs of intermittent exercise. AB - To date, steady state models represent the only acceptable methodology for the estimation of exercise energy costs. Conversely, comparisons made between continuous and intermittent exercise generally reveal major physiological discrepancies, leading to speculation as to why steady state energy expenditure models should be applied to intermittent exercise. Under intermittent conditions, skeletal muscle invokes varying aerobic and anaerobic metabolic responses, each with the potential to make significant contributions to overall energy costs. We hypothesize that if the aerobic-only energetic profile of steady state exercise can be used to estimate the energetics of non-steady state and intermittent exercise, then the converse also must be true. In fact, reasonable estimates of energy costs to work volumes or work rates can be demonstrated under steady state, non-steady state and intermittent conditions; the problem with the latter two is metabolic variability. Using resistance training as a model, estimates of both aerobic and anaerobic energy cost components, as opposed to one or the other, have reduced the overall energetic variability that appears inherent to brief, intense, intermittent exercise models. PMID- 24235989 TI - Physical and physiological characteristics of elite male handball players from teams with a different ranking. AB - The aim of this study was to examine possible discriminant physical and physiological characteristics between elite male handball players from elite teams with different league rankings. Players from three teams (A, B and C), which competed in the first league of the Greek championship during the season 2011-2012 participated in the study. Team A finished first, B came second and C came eighth out of eleven clubs. Teams A and B also participated in European Cups, and team A won the European Challenge Cup. The players (n=44) were examined for anthropometric characteristics and performed a series of physical fitness tests. Players from teams A and B were taller (6.2 cm (0.7;11.7), mean difference (95% CI) and 9.2 cm (4.0;14.5), respectively), and had a higher amount of fat free mass (6.4 kg (1.1;11.8) and 5.4 kg (0.2;10.5)) compared to those of team C. Players from team A performed better than players from team C in the squat jump (5.5 cm (1.0;10.0)), the countermovement jump without (5.5 cm (0.4;10.6)) and with arm-swing (6.0 cm (0.7;11.3)) and in the 30 s Bosco test (5.7 W.kg-1 (1.2;10.2)). Also, players from team A outperformed team B in mean power during the Wingate anaerobic test (WAnT, 0.5 W.kg-1(0;0.9)) and in the Bosco test (7.8 W.kg-1 (3.4;12.2)). Overall, players from the best ranked team performed better than the lowest ranked team on WAnT, vertical jumps and the Bosco test. Stepwise discriminant analysis showed that stature and mean power during the Bosco test were the most important characteristics in TH players, accounting for 54.6% of the variance in team ranking. These findings indicate the contribution of particular physical fitness components (stature, fat free mass and anaerobic power) to excellence in TH. In addition, the use of the Bosco test as an assessment tool in talent identification and physical fitness monitoring in this sport is further recommended. PMID- 24235990 TI - Calculating Home Advantage in the First Decade of the 21th Century UEFA Soccer Leagues. AB - Home advantage has been studied in different sports, establishing its existence and its possible causes. This article analyzes the home advantage in soccer leagues of UEFA countries in the first part of the 21st century. The sample of 52 countries monitored during a period of 10 years allows us to study 520 leagues and 111,030 matches of the highest level in each country associated with UEFA. Home advantage exists and is significant in 32 of the 52 UEFA countries, where it equals 55.6%. A decrease can be observed in the tendency towards home advantage between the years 2000 and 2010. Values between 55 and 56 were observed for home advantage in the top ten leagues in Europe. It has also been observed that home advantage depends on the level of the league evaluated using UEFA's 2010/11 Country coefficients. The home advantage is calculated taking into account the teams' position and the points obtained in each of the leagues. A direct relationship was observed with the number of points gained and an inverse relationship was observed with the team position. PMID- 24235991 TI - The importance of sports performance factors and training contents from the perspective of futsal coaches. AB - The aim of this study was to identify the importance assigned by futsal coaches with different education levels to the sports performance factors (technical, tactical, physical and psychological) and to the training contents. The sample was divided into three groups (novice: n=35, intermediate: n=42; and elite coaches: n=15) depending on the degree of specific education, coaching experience and the level of the teams trained. To achieve this goal, the coaches answered a questionnaire previously validated by specialists in sport sciences. The results showed significant differences between the novice and elite group in small-sided games, inferiority games, opposition and execution timing of the training and drill items. The analyses also showed significant differences between the novice and intermediate group in inferiority games and opposition of the training and drill items. Although, no differences were identified between groups for the remaining performance factors and training and drill items considered, the identified trends provide a baseline related to the knowledge that contributes to the development of expertise of futsal coaches. PMID- 24235992 TI - Relationship between fatigue index and number of repetition maxima with sub maximal loads in biceps curl. AB - The aim of this study was to investigate the relationship between the number of repetition maxima to volitional failure (RM) at 60%, 75%, 90% of 1RM and fatigue index (FI), a determinant of the muscular endurance level. Thirty four resistance trained male participants attended two testing sessions. The first session was conducted to assess 1RM load and RM at 60%, 75% and 90% of 1RM in the supine biceps curl (SBC) exercise. In the second session, a FI test protocol consisting of five sets of SBC with 90 s rest between sets was performed to determine FI values. Each set was performed to volitional failure using a sub-maximal load in the range of 15-20RM. Hypothetical high FI and low FI groups (17 participants with the highest and lowest FI values, respectively) were formed for statistical analyses. ANOVA results revealed that RM at 60%, 75%, 90% of 1RM were not significantly different between FI groups when controlled for mean repetition tempo (p=0.11, p=0.38, p=0.13, respectively). Pearson's correlation coefficients revealed that no significant relationship was present between FI values and RM at 60%, 75%, 90% of 1RM (p=0.40, p=0.46, p=0.14, respectively). In conclusion, the muscular endurance level of participants defined in terms of FI value was not an indicator of RM in SBC. Therefore, athletes with different muscular endurance levels can use similar percentages of 1RM in biceps curl exercise in their training programs when the aim is to elicit training adaptations related to specific RM zones. PMID- 24235993 TI - A decade of euroleague basketball: an analysis of trends and recent rule change effects. AB - The International Basketball Federation (FIBA) recently introduced major rule changes that came into effect with the 2010/11 season. Most notably, moving the three-point arc and changing the shot-clock. The purpose of this study was to investigate and quantify how these changes affect the game performance of top level European basketball players. In order to better understand these changes, we also investigated past seasons and showed the presence of several trends, even in the absence of significant rule changes. A large set of game statistics for 10 seasons and 2198 Euroleague basketball games in which top European clubs competed was analyzed. Results show that the effects of the rule changes are contrary to trends in recent years. PMID- 24235994 TI - The influence of an additional load on time and force changes in the ground reaction force during the countermovement vertical jump. AB - The aim of this study was to determine how an additional load influences the force-vs-time relationship of the countermovement vertical jump (CMVJ). The participants that took part in the experiment were 18 male university students who played sport recreationally, including regular games of volleyball. They were asked to perform a CMVJ without involving the arms under four conditions: without and with additional loads of 10%, 20%, and 30% of their body weight (BW). The vertical component of the ground reaction force (GRF) was measured by a force plate. The GRF was used to calculate the durations of the preparatory, braking, and acceleration phases, the total duration of the jump, force impulses during the braking and acceleration phases, average forces during the braking and acceleration phases, and the maximum force of impact at landing. Results were evaluated using repeated-measures ANOVA. Increasing the additional load prolonged both the braking and acceleration phases of the jump, with statistically significant changes in the duration of the acceleration phase found for an additional load of 20% BW. The magnitude of the force systematically and significantly increased with the additional load. The force impulse during the acceleration phase did not differ significantly between jumps performed with loads of 20% and 30% BW. The results suggest that the optimal additional load for developing explosive strength in vertical jumping ranges from 20% to 30% of BW, with this value varying between individual subjects. PMID- 24235995 TI - Activity profiles of soccer players during the 2010 world cup. AB - The main objective of this study was to analyse the distance covered and the activity profile that players presented at the FIFA World Cup in 2010. Complementarily, the distance covered by each team within the same competition was analysed. For the purposes of this study 443 players were analysed, of which 35 were goalkeepers, 84 were external defenders, 77 were central defenders, 182 were midfielders, and 65 were forwards. Afterwards, a thorough analysis was performed on 16 teams that reached the group stage, 8 teams that achieved the round of 16, 4 teams that reached the quarter-finals, and 4 teams that qualified for the semi-finals and finals. A comparison of the mean distance covered per minute among the playing positions showed statistically significant differences (F(4,438) = 559.283; p < 0.001; 2 = 0.836; Power = 1.00). A comparison of the activity time among tactical positions also resulted in statistically significant differences, specifically, low activity (F(4,183.371) = 1476.844; p < 0.001; 2 = 0.742; Power = 1.00), medium activity (F(4,183.370) = 1408.106; p < 0.001; 2 = 0.731; Power = 1.00), and high activity (F(4,182.861) = 1152.508; p < 0.001; 2 = 0.703; Power = 1.00). Comparing the mean distance covered by teams, differences that are not statistically significant were observed (F(3,9.651) = 4.337; p < 0.035; 2 = 0.206; Power = 0.541). In conclusion, the tactical positions of the players and their specific tasks influence the activity profile and physical demands during a match. PMID- 24235996 TI - Performance consistency of international soccer teams in euro 2012: a time series analysis. AB - The purpose of this study was to examine the consistency of performance in successive matches for international soccer teams from Europe which qualified for the quarter final stage of EURO 2012 in Poland and Ukraine. The eight teams that reached the quarter final stage and beyond were the sample teams for this time series analysis. The autocorrelation and cross-correlation functions were used to analyze the consistency of play and its association with the result of match in sixteen performance indicators of each team. The results of autocorrelation function showed that based on the number of consistent performance indicators, Spain and Italy demonstrated more consistency in successive matches in relation to other teams. This appears intuitive given that Spain played Italy in the final. However, it is arguable that other teams played at a higher performance levels at various parts of the competition, as opposed to performing consistently throughout the tournament. The results of the cross-correlation analysis showed that in relation to goal-related indicators, these had higher associations with the match results of Spain and France. In relation to the offensive-related indicators, France, England, Portugal, Greece, Czech Republic and Spain showed a positive correlation with the match result. In relation to the defensive-related indicators, France, England, Greece and Portugal showed a positive correlation with match results. In conclusion, in an international soccer tournament, the successful teams displayed a greater degree of performance consistency across all indicators in comparison to their competitors who occasionally would show higher levels of performance in individual games, yet not consistently across the overall tournament. The authors therefore conclude that performance consistency is more significant in international tournament soccer, versus occasionally excelling in some metrics and indicators in particular games. PMID- 24235997 TI - Ball Possession Effectiveness in Men's Elite Floorball According to Quality of Opposition and Game Period. AB - The aim of the present study was to identify the importance of floorball tactical variables to predict ball possession effectiveness, when controlling quality of opposition and game periods. The sample was composed by 1500 ball possessions, corresponding to 14 games randomly selected from the International Championships played during 2008 and 2010 (World Championship, Four nations tournament and classificatory phases for World Championship) by teams from different competition levels (HIGH, INTERMEDIATE and LOW). The effects of the predictor variables on successful ball possessions according to the three game contexts (HIGH vs. HIGH; HIGH vs. LOW; LOW vs. LOW games) were analyzed using Binomial Logistic Regressions. The results showed no interaction with the game period. In HIGH vs. HIGH games, quality of opposition showed an association with ball possession effectiveness with ending zone, offensive system, possession duration, height of shooting and defensive pressures previous to the shot. In HIGH vs. LOW games the important factors were the starting zone, possession duration, defensive pressure previous to the last pass and to the shot, technique of shooting and the number players involved in each ball possession. Finally, in LOW vs. LOW games, the results emphasized the importance of starting and ending zones, the number of passes used and the technique of shooting. In conclusion, elite floorball performance is mainly affected by quality of opposition showing different game patterns in each context that should be considered by coaches when preparing practices and competitions. PMID- 24235998 TI - No Association between Circulating Levels and Genetic Variants of IL-6 and TNF alpha and Colon Adenoma. AB - BACKGROUND & AIMS: Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha), two important inflammatory cytokines, have been inconsistently associated with risk of colon neoplasia in epidemiological studies. However, research to date has not adequately assessed whether race-specific differences may exist in associations between biomarkers and genetic variants of these cytokines and colorectal adenoma - the precursor lesions of colorectal cancer. We sought to determine whether circulating levels of IL-6 and TNF-alpha, or genetic polymorphisms in IL-6and TNF-alpha were associated with colon adenoma and if so, whether that association differed by race. METHODS: We analyzed the associations of circulating levels and single nucleotide polymorphisms (SNPs) of IL-6 and TNF alpha with risk of colon adenomas in a colonoscopy -based case-control study of 401 incident adenoma cases and 1,050 controls. We used multivariate unconditional logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for levels or genotypes (log additive models) of IL-6 and TNF alpha. RESULTS: Compared to the bottom tertile of IL-6, the adjusted ORs were: 1.06 (0.75-1.44), 1.01 (0.72-1.40), respectively for the 2nd and 3rd tertiles (ptrend = 0.10); the corresponding ORs for TNF-alpha were: 0.85 (0.63-1.15) and 1.01 (0.75-1.36), respectively (ptrend = 0.39). Race-stratified analyses did not reveal any significant association. There were also no statistically significant associations between IL-6 and TNF-alpha SNPs and colon adenoma. CONCLUSIONS: Our results do not support pre-diagnostic levels of IL-6, TNF-alpha or their genetic variants as significant risk factors for the development of colon adenoma. PMID- 24236005 TI - Does the adequacy parameter Kt/V(urea) reflect uremic toxin concentrations in hemodialysis patients? AB - Hemodialysis aims at removing uremic toxins thus decreasing their concentrations. The present study investigated whether Kt/V(urea), used as marker of dialysis adequacy, is correlated with these concentrations. Predialysis blood samples were taken before a midweek session in 71 chronic HD patients. Samples were analyzed by colorimetry, HPLC, or ELISA for a broad range of uremic solutes. Solute concentrations were divided into four groups according to quartiles of Kt/V(urea), and also of different other parameters with potential impact, such as age, body weight (BW), Protein equivalent of Nitrogen Appearance (PNA), Residual Renal Function (RRF), and dialysis vintage. Dichotomic concentration comparisons were performed for gender and Diabetes Mellitus (DM). Analysis of Variance in quartiles of Kt/V(urea) did not show significant differences for any of the solute concentrations. For PNA, however, concentrations showed significant differences for urea (P<0.001), uric acid (UA), p-cresylsulfate (PCS), and free PCS (all P<0.01), and for creatinine (Crea) and hippuric acid (HA) (both P<0.05). For RRF, concentrations varied for beta2-microglobulin (P<0.001), HA, free HA, free indoxyl sulfate, and free indole acetic acid (all P<0.01), and for p cresylglucuronide (PCG), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), free PCS, and free PCG (all P<0.05). Gender and body weight only showed differences for Crea and UA, while age, vintage, and diabetes mellitus only showed differences for one solute concentration (UA, UA, and free PCS, respectively). Multifactor analyses indicated a predominant association of concentration with protein intake and residual renal function. In conclusion, predialysis concentrations of uremic toxins seem to be dependent on protein equivalent of nitrogen appearance and residual renal function, and not on dialysis adequacy as assessed by Kt/V(urea). Efforts to control intestinal load of uremic toxin precursors by dietary or other interventions, and preserving RRF seem important approaches to decrease uremic solute concentration and by extension their toxicity. PMID- 24236006 TI - Quantitative network measures as biomarkers for classifying prostate cancer disease states: a systems approach to diagnostic biomarkers. AB - Identifying diagnostic biomarkers based on genomic features for an accurate disease classification is a problem of great importance for both, basic medical research and clinical practice. In this paper, we introduce quantitative network measures as structural biomarkers and investigate their ability for classifying disease states inferred from gene expression data from prostate cancer. We demonstrate the utility of our approach by using eigenvalue and entropy-based graph invariants and compare the results with a conventional biomarker analysis of the underlying gene expression data. PMID- 24236007 TI - Beliefs about lying and spreading of dishonesty: undetected lies and their constructive and destructive social dynamics in dice experiments. AB - Field experiments have shown that observing other people littering, stealing or lying can trigger own misconduct, leading to a decay of social order. However, a large extent of norm violations goes undetected. Hence, the direction of the dynamics crucially depends on actors' beliefs regarding undetected transgressions. Because undetected transgressions are hardly measureable in the field, a laboratory experiment was developed, where the complete prevalence of norm violations, subjective beliefs about them, and their behavioral dynamics is measurable. In the experiment, subjects could lie about their monetary payoffs, estimate the extent of liars in their group and make subsequent lies contingent on information about other people's lies. Results show that informed people who underestimate others' lying increase own lying more than twice and those who overestimate, decrease it by more than half compared to people without information about others' lies. This substantial interaction puts previous results into perspective, showing that information about others' transgressions can trigger dynamics in both directions: the spreading of normative decay and restoring of norm adherence. PMID- 24236008 TI - To dope or not to dope: neuroenhancement with prescription drugs and drugs of abuse among Swiss university students. AB - BACKGROUND: Neuroenhancement is the use of substances by healthy subjects to enhance mood or cognitive function. The prevalence of neuroenhancement among Swiss university students is unknown. Investigating the prevalence of neuroenhancement among students is important to monitor problematic use and evaluate the necessity of prevention programs. STUDY AIM: To describe the prevalence of the use of prescription medications and drugs of abuse for neuroenhancement among Swiss university students. METHOD: In this cross-sectional study, students at the University of Zurich, University of Basel, and Swiss Federal Institute of Technology Zurich were invited via e-mail to participate in an online survey. RESULTS: A total of 28,118 students were contacted, and 6,275 students completed the survey. Across all of the institutions, 13.8% of the respondents indicated that they had used prescription drugs (7.6%) or drugs of abuse including alcohol (7.8%) at least once specifically for neuroenhancement. The most frequently used prescription drugs for neuroenhancement were methylphenidate (4.1%), sedatives (2.7%), and beta-blockers (1.2%). Alcohol was used for this purpose by 5.6% of the participants, followed by cannabis (2.5%), amphetamines (0.4%), and cocaine (0.2%). Arguments for neuroenhancement included increased learning (66.2%), relaxation or sleep improvement (51.2%), reduced nervousness (39.1%), coping with performance pressure (34.9%), increased performance (32.2%), and experimentation (20%). Neuroenhancement was significantly more prevalent among more senior students, students who reported higher levels of stress, and students who had previously used illicit drugs. Although "soft enhancers", including coffee, energy drinks, vitamins, and tonics, were used daily in the month prior to an exam, prescription drugs or drugs of abuse were used much less frequently. CONCLUSIONS: A significant proportion of Swiss university students across most academic disciplines reported neuroenhancement with prescription drugs and drugs of abuse. However, these substances are rarely used on a daily basis and more sporadically used prior to exams. PMID- 24236009 TI - The role of Surinamese migrants in the transmission of Chlamydia trachomatis between Paramaribo, Suriname and Amsterdam, The Netherlands. AB - The large Surinamese migrant population in the Netherlands is a major risk group for urogenital Chlamydia trachomatis infection. Suriname, a former Dutch colony, also has a high prevalence of C. trachomatis. Surinamese migrants travel extensively between the Netherlands and Suriname. Our objective was to assess whether the Surinamese migrants in the Netherlands form a bridge population facilitating transmission of C. trachomatis between Suriname and the Netherlands. If so, joint prevention campaigns involving both countries might be required. Between March 2008 and July 2010, participants were recruited at clinics in Paramaribo, Suriname and in Amsterdam, the Netherlands. Participants were grouped as native Surinamese, native Dutch, Surinamese migrant, Dutch migrant, or Other, based on country of residence and country of birth of the participant and of their parents. Risk behavior, such as sexual mixing between ethnic groups, was recorded and C. trachomatis positive samples were typed through multilocus sequence typing (MLST). A minimum spanning tree of samples from 426 participants showed four MLST clusters. The MLST strain distribution of Surinamese migrants differed significantly from both the native Surinamese and Dutch populations, but was not an intermediate state between these two populations. Sexual mixing between the Surinamese migrants and the Dutch and Surinamese natives occurred frequently. Yet, the MLST cluster distribution did not differ significantly between participants who mixed and those who did not. Sexual mixing occurred between Surinamese migrants in Amsterdam and the native populations of Suriname and the Netherlands. These migrants, however, did not seem to form an effective bridge population for C. trachomatis transmission between the native populations. Although our data do not seem to justify the need for joint campaigns to reduce the transmission of C. trachomatis strains between both countries, intensified preventive campaigns to decrease the C. trachomatis burden are required, both in Suriname and in the Netherlands. PMID- 24236010 TI - Antiretroviral therapy reduces HIV transmission in discordant couples in rural Yunnan, China. AB - BACKGROUND: Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. METHODS: A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/ul). Seroconversion was used to determine HIV incidence. RESULTS: A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naive HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12-0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. CONCLUSIONS: ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region. PMID- 24236011 TI - Earliest stone-tipped projectiles from the Ethiopian rift date to >279,000 years ago. AB - Projectile weapons (i.e. those delivered from a distance) enhanced prehistoric hunting efficiency by enabling higher impact delivery and hunting of a broader range of animals while reducing confrontations with dangerous prey species. Projectiles therefore provided a significant advantage over thrusting spears. Composite projectile technologies are considered indicative of complex behavior and pivotal to the successful spread of Homo sapiens. Direct evidence for such projectiles is thus far unknown from >80,000 years ago. Data from velocity dependent microfracture features, diagnostic damage patterns, and artifact shape reported here indicate that pointed stone artifacts from Ethiopia were used as projectile weapons (in the form of hafted javelin tips) as early as >279,000 years ago. In combination with the existing archaeological, fossil and genetic evidence, these data isolate eastern Africa as a source of modern cultures and biology. PMID- 24236013 TI - A remarkable new species of Liparis (Orchidaceae) from China and its phylogenetic implications. AB - In the present study, we formally describe Liparis pingxiangensis as a new species from Guangxi, China on the basis of morphological and molecular phylogenetic analyses. It is easily distinguished from closely related species by strongly curved column without column wings, and broadly rhombic-elliptic lip with 2 uncinate calli at the base. In particular, it differs most markedly from its congeners in possessing two pollinia attached by long and prominent caudicles (not stipes), to a distinct sticky disc. This type of pollinarium, as far as we know, is not found in any other species of Liparis, and is also unique among the orchids with waxy pollinia. We then proceeded to a phylogenetic analysis to ascertain the systematic position of this enigmatic species. Molecular study based on nuclear ribosomal ITS and plastid matK DNA sequence data supports L. pingxiangensis as a distinct species, which forms an independent lineage sister to L. nervosa and its allies (93% BS, 1.00 BPP). In the light of previous work, the findings have important implications for a better understanding of the well supported pattern mainly based on vegetative features in Malaxideae. PMID- 24236012 TI - L-plastin nanobodies perturb matrix degradation, podosome formation, stability and lifetime in THP-1 macrophages. AB - Podosomes are cellular structures acting as degradation 'hot-spots' in monocytic cells. They appear as dot-like structures at the ventral cell surface, enriched in F-actin and actin regulators, including gelsolin and L-plastin. Gelsolin is an ubiquitous severing and capping protein, whereas L-plastin is a leukocyte specific actin bundling protein. The presence of the capping protein CapG in podosomes has not yet been investigated. We used an innovative approach to investigate the role of these proteins in macrophage podosomes by means of nanobodies or Camelid single domain antibodies. Nanobodies directed against distinct domains of gelsolin, L-plastin or CapG were stably expressed in macrophage-like THP-1 cells. CapG was not enriched in podosomes. Gelsolin nanobodies had no effect on podosome formation or function but proved very effective in tracing distinct gelsolin populations. One gelsolin nanobody specifically targets actin-bound gelsolin and was effectively enriched in podosomes. A gelsolin nanobody that blocks gelsolin-G-actin interaction was not enriched in podosomes demonstrating that the calcium-activated and actin-bound conformation of gelsolin is a constituent of podosomes. THP-1 cells expressing inhibitory L-plastin nanobodies were hampered in their ability to form stable podosomes. Nanobodies did not perturb Ser5 phosphorylation of L-plastin although phosphorylated L-plastin was highly enriched in podosomes. Furthermore, nanobody induced inhibition of L-plastin function gave rise to an irregular and unstable actin turnover of podosomes, resulting in diminished degradation of the underlying matrix. Altogether these results indicate that L-plastin is indispensable for podosome formation and function in macrophages. PMID- 24236014 TI - Small thaw ponds: an unaccounted source of methane in the Canadian high Arctic. AB - Thawing permafrost in the Canadian Arctic tundra leads to peat erosion and slumping in narrow and shallow runnel ponds that surround more commonly studied polygonal ponds. Here we compared the methane production between runnel and polygonal ponds using stable isotope ratios, 14C signatures, and investigated potential methanogenic communities through high-throughput sequencing archaeal 16S rRNA genes. We found that runnel ponds had significantly higher methane and carbon dioxide emissions, produced from a slightly larger fraction of old carbon, compared to polygonal ponds. The methane stable isotopic signature indicated production through acetoclastic methanogenesis, but gene signatures from acetoclastic and hydrogenotrophic methanogenic Archaea were detected in both polygonal and runnel ponds. We conclude that runnel ponds represent a source of methane from potentially older C, and that they contain methanogenic communities able to use diverse sources of carbon, increasing the risk of augmented methane release under a warmer climate. PMID- 24236015 TI - Sputum inflammatory profile before and after specific inhalation challenge in individuals with suspected occupational asthma. AB - BACKGROUND: The aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B4 (LTB4) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular weight (LMW) agents. MATERIAL AND METHODS: Fifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB4 and a 10 Th1/Th2 cytokines were measured in sputum supernatant. RESULTS: Thirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB4 level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146). CONCLUSION: When conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents. PMID- 24236016 TI - Meta-analysis of fluid intelligence tests of children from the Chinese mainland with learning difficulties. AB - OBJECTIVE: To evaluate the differences in fluid intelligence tests between normal children and children with learning difficulties in China. METHOD: PubMed, MD Consult, and other Chinese Journal Database were searched from their establishment to November 2012. After finding comparative studies of Raven measurements of normal children and children with learning difficulties, full Intelligent Quotation (FIQ) values and the original values of the sub-measurement were extracted. The corresponding effect model was selected based on the results of heterogeneity and parallel sub-group analysis was performed. RESULTS: Twelve documents were included in the meta-analysis, and the studies were all performed in mainland of China. Among these, two studies were performed at child health clinics, the other ten sites were schools and control children were schoolmates or classmates. FIQ was evaluated using a random effects model. WMD was -13.18 (95% CI: -16.50- -9.85). Children with learning difficulties showed significantly lower FIQ scores than controls (P<0.00001); Type of learning difficulty and gender differences were evaluated using a fixed-effects model (I2 = 0%). The sites and purposes of the studies evaluated here were taken into account, but the reasons of heterogeneity could not be eliminated; The sum IQ of all the subgroups showed considerable heterogeneity (I2 = 76.5%). The sub-measurement score of document A showed moderate heterogeneity among all documents, and AB, B, and E showed considerable heterogeneity, which was used in a random effect model. Individuals with learning difficulties showed heterogeneity as well. There was a moderate delay in the first three items (-0.5 to -0.9), and a much more pronounced delay in the latter three items (-1.4 to -1.6). CONCLUSION: In the Chinese mainland, the level of fluid intelligence of children with learning difficulties was lower than that of normal children. Delayed development in sub items of C, D, and E was more obvious. PMID- 24236017 TI - Paleoindian unifacial stone tool 'spurs': intended accessories or incidental accidents? AB - Paleoindian unifacial stone tools frequently exhibit distinct, sharp projections, known as "spurs". During the last two decades, a theoretically and empirically informed interpretation-based on individual artifact analysis, use-wear, tool production techniques, and studies of resharpening-suggested that spurs were sometimes created intentionally via retouch, and other times created incidentally via resharpening or knapping accidents. However, more recently Weedman strongly criticized the inference that Paleoindian spurs were ever intentionally produced or served a functional purpose, and asserted that ethnographic research "demonstrates that the presence of so called 'graver' spurs does not have a functional significance." While ethnographic data cannot serve as a direct test of the archaeological record, we used Weedman's ethnographic observations to create two quantitative predictions of the Paleoindian archaeological record in order to directly examine the hypothesis that Paleoindian spurs were predominantly accidents occurring incidentally via resharpening and reshaping. The first prediction is that the frequency of spurs should increase as tool reduction proceeds. The second prediction is that the frequency of spurs should increase as tool breakage increases. An examination of 563 unbroken tools and 629 tool fragments from the Clovis archaeological record of the North American Lower Great Lakes region showed that neither prediction was consistent with the notion that spurs were predominately accidents. Instead, our results support the prevailing viewpoint that spurs were sometimes created intentionally via retouch, and other times, created incidentally via resharpening or knapping accidents. Behaviorally, this result is consistent with the notion that unifacial stone tools were multifunctional implements that enhanced the mobile lifestyle of Pleistocene hunter-gatherers. PMID- 24236018 TI - Association analysis identifies Melampsora *columbiana poplar leaf rust resistance SNPs. AB - Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora *columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05) with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca2+/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism. PMID- 24236019 TI - Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis? AB - The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA 1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention. PMID- 24236020 TI - Role of upwelling on larval dispersal and productivity of gooseneck barnacle populations in the Cantabrian Sea: management implications. AB - The effect of coastal upwelling on the recruitment and connectivity of coastal marine populations has rarely been characterized to a level of detail to be included into sound fishery management strategies. The gooseneck barnacle (Pollicipes pollicipes) fishery at the Cantabrian Coast (Northern Spain) is located at the fringes of the NW Spanish Upwelling system. This fishery is being co-managed through a fine-scale, interspersed set of protected rocks where each rock receives a distinct level of protection. Such interspersion is potentially beneficial, but the extent to which such spacing is consistent with mean larval dispersal distances is as yet unknown. We have simulated the spread of gooseneck barnacle larvae in the Central Cantabrian Coast using a high-resolution time series of current profiles measured at a nearshore location. During a year of high upwelling activity (2009), theoretical recruitment success was 94% with peak recruitment predicted 56 km west of the emission point. However, for a year of low upwelling activity (2011) theoretical recruitment success dropped to 15.4% and peak recruitment was expected 13 km east of the emission point. This is consistent with a positive correlation between catch rates and the Integrated Upwelling Index, using a 4-year lag to allow recruits to reach commercial size. Furthermore, a net long-term westward larval transport was estimated by means of mitochondrial cytochrome c oxidase subunit I (COI) sequences for five populations in the Cantabrian Sea. Our results call into question the role of long distance dispersal, driven by the mesoscale processes in the area, in gooseneck barnacle populations and point to the prevalent role of small-scale, asymmetric connectivity more consistent with the typical scale of the co-management process in this fishery. PMID- 24236021 TI - Ponatinib is a pan-BCR-ABL kinase inhibitor: MD simulations and SIE study. AB - BCR-ABL kinase domain inhibition can be used to treat chronic myeloid leukemia. The inhibitors such as imatinib, dasatinib and nilotinib are effective drugs but are resistant to some BCR-ABL mutations. The pan-BCR-ABL kinase inhibitor ponatinib exhibits potent activity against native, T315I, and all other clinically relevant mutants, and showed better inhibition than the previously known inhibitors. We have studied the molecular dynamics simulations and calculated solvated interaction energies of native and fourteen mutant BCR-ABL kinases (M244V, G250E, Q252H, Y253F, Y253H, E255K, E255V, T315A, T315I, F317L, F317V, M351T, F359V and H396P) complexed with ponatinib. These studies revealed that the interactions between ponatinib and individual residues in BCR-ABL kinase are also affected due to the remote residue mutations. We report that some residues, Met244, Lys245, Gln252, Gly254, Leu370 and Leu298 do not undergo any conformational changes, while the fluctuations in residues from P-loop, beta3-, beta5- strands and alphaC- helix are mainly responsible for ponatinib binding to native and all mutant BCR-ABL kinases. Our work provides the molecular mechanisms of native and mutant BCR-ABL kinases inhibition by ponatinib at atomic level that has not been studied before. PMID- 24236022 TI - Alterations of glucose-dependent insulinotropic polypeptide and expression of genes involved in mammary gland and adipose tissue lipid metabolism during pregnancy and lactation. AB - Gastric inhibitory polypeptide (GIP) is a gut derived peptide with multiple emerging physiological actions. Effects of pregnancy and lactation on GIP secretion and related gene expression were studied in Wistar rats. Pregnancy moderately increased feeding (p<0.05), whilst lactation substantially increased food intake (p<0.01 to p<0.001). Circulating GIP was unchanged during pregnancy, but non-fasting plasma glucose was significantly (p<0.01) decreased and insulin increased (p<0.05). Lactation was associated with elevated circulating GIP concentrations (p<0.001) without change of glucose or insulin. Oral glucose resulted in a significantly (p<0.001) decreased glycaemic excursion despite similar glucose-induced GIP and insulin concentrations in lactating rats. Pregnant rats had a similar glycaemic excursion but exhibited significantly lowered (p<0.05) GIP accompanied by elevated (p<0.001) insulin levels. Pregnant rats exhibited increased (p<0.001) islet numbers and individual islet areas were enlarged (p<0.05). There were no significant differences in islet alpha-cell areas, but all groups of rats displayed co-expression of glucagon and GIP in alpha-cells. Lactating rats exhibited significantly (p<0.01) increased intestinal weight, whereas intestinal GIP stores were significantly (p<0.01) elevated only in pregnant rats. Gene expression studies in lactating rats revealed prominent (p<0.01 to p<0.001) increases in mammary gland expression of genes involved in energy turnover, including GIP-R. GIP was present in intestines and plasma of 17 day old foetal rats, with substantially raised circulating concentrations in neonates throughout the period of lactation/suckling. These data indicate that changes in the secretion and action of GIP play an important role in metabolic adaptations during pregnancy and especially lactation. PMID- 24236023 TI - In situ preparation of biomimetic thin films and their surface-shielding effect for organisms in high vacuum. AB - Self-standing biocompatible films have yet to be prepared by physical or chemical vapor deposition assisted by plasma polymerization because gaseous monomers have thus far been used to create only polymer membranes. Using a nongaseous monomer, we previously found a simple fabrication method for a free-standing thin film prepared from solution by plasma polymerization, and a nano-suit made by polyoxyethylene (20) sorbitan monolaurate can render multicellular organisms highly tolerant to high vacuum. Here we report thin films prepared by plasma polymerization from various monomer solutions. The films had a flat surface at the irradiated site and were similar to films produced by vapor deposition of gaseous monomers. However, they also exhibited unique characteristics, such as a pinhole-free surface, transparency, solvent stability, flexibility, and a unique out-of-plane molecular density gradient from the irradiated to the unirradiated surface of the film. Additionally, covering mosquito larvae with the films protected the shape of the organism and kept them alive under the high vacuum conditions in a field emission-scanning electron microscope. Our method will be useful for numerous applications, particularly in the biological sciences. PMID- 24236024 TI - Priming of soil carbon decomposition in two Inner Mongolia grassland soils following sheep dung addition: a study using 13C natural abundance approach. AB - To investigate the effect of sheep dung on soil carbon (C) sequestration, a 152 days incubation experiment was conducted with soils from two different Inner Mongolian grasslands, i.e. a Leymus chinensis dominated grassland representing the climax community (2.1% organic matter content) and a heavily degraded Artemisia frigida dominated community (1.3% organic matter content). Dung was collected from sheep either fed on L. chinensis (C3 plant with delta13C = 26.80/00; dung delta13C = -26.20/00) or Cleistogenes squarrosa (C4 plant with delta13C = -14.60/00; dung delta13C = -15.70/00). Fresh C3 and C4 sheep dung was mixed with the two grassland soils and incubated under controlled conditions for analysis of 13C-CO2 emissions. Soil samples were taken at days 17, 43, 86, 127 and 152 after sheep dung addition to detect the delta13C signal in soil and dung components. Analysis revealed that 16.9% and 16.6% of the sheep dung C had decomposed, of which 3.5% and 2.8% was sequestrated in the soils of L. chinensis and A. frigida grasslands, respectively, while the remaining decomposed sheep dung was emitted as CO2. The cumulative amounts of C respired from dung treated soils during 152 days were 7-8 times higher than in the un-amended controls. In both grassland soils, ca. 60% of the evolved CO2 originated from the decomposing sheep dung and 40% from the native soil C. Priming effects of soil C decomposition were observed in both soils, i.e. 1.4 g and 1.6 g additional soil C kg-1 dry soil had been emitted as CO2 for the L. chinensis and A. frigida soils, respectively. Hence, the net C losses from L. chinensis and A. frigida soils were 0.6 g and 0.9 g C kg-1 soil, which was 2.6% and 7.0% of the total C in L. chinensis and A. frigida grasslands soils, respectively. Our results suggest that grazing of degraded Inner Mongolian pastures may cause a net soil C loss due to the positive priming effect, thereby accelerating soil deterioration. PMID- 24236026 TI - Uganda's new national laboratory sample transport system: a successful model for improving access to diagnostic services for Early Infant HIV Diagnosis and other programs. AB - INTRODUCTION: Uganda scaled-up Early HIV Infant Diagnosis (EID) when simplified methods for testing of infants using dried blood spots (DBS) were adopted in 2006 and sample transport and management was therefore made feasible in rural settings. Before this time only 35% of the facilities that were providing EID services were reached through the national postal courier system, Posta Uganda. The transportation of samples during this scale-up, therefore, quickly became a challenge and varied from facility to facility as different methods were used to transport the samples. This study evaluates a novel specimen transport network system for EID testing. METHODS: A retrospective study was done in mid-2012 on 19 pilot hubs serving 616 health facilities in Uganda. The effect on sample-result turnaround time (TAT) and the cost of DBS sample transport on 876 sample-results was analyzed. RESULTS: The HUB network system provided increased access to EID services ranging from 36% to 51%, drastically reduced transportation costs by 62%, reduced turn-around times by 46.9% and by a further 46.2% through introduction of SMS printers. CONCLUSIONS: The HUB model provides a functional, reliable and efficient national referral network against which other health system strengthening initiatives can be built to increase access to critical diagnostic and treatment monitoring services, improve the quality of laboratory and diagnostic services, with reduced turn-around times and improved quality of prevention and treatment programs thereby reducing long-term costs. PMID- 24236025 TI - Development of a highly sensitive immuno-PCR assay for the measurement of alpha galactosidase A protein levels in serum and plasma. AB - Fabry disease is an X-linked genetic disorder caused by defects in the alpha galactosidase A (GLA) gene, and heterogeneous mutations lead to quantitative and/or qualitative defects in GLA protein in male patients with Fabry disease. Random X-chromosomal inactivation modifies the clinical and biochemical features of female patients with Fabry disease. Functional polymorphisms have been frequently reported in recent times, and these increase the difficulty of understanding the pathogenetic basis of the disease. To date, GLA protein level has been measured using an enzyme-linked immunosorbent assay (ELISA). However, ELISA is not highly sensitive due to the high background noise. In this paper, we introduce a novel application of the immuno-polymerase chain reaction (PCR) method (termed Multiple Simultaneous Tag [MUSTag]) for measurement of the GLA protein level in blood samples. We compared the sensitivities of the MUSTag method with plates or magnetic beads with those of ELISA for recombinant human GLA and found that the apparent maximal sensitivity was higher for the former than for the latter. We then measured the GLA concentrations in serum and plasma from male patients with classic Fabry disease (Male Fabry), females with Fabry disease (Female Fabry), male subjects harboring the functional polymorphism p.E66Q (E66Q), and control (Control) subjects. Our results revealed that compared to the MUSTag plate and ELISA, the MUSTag beads assay afforded a clearer estimation of the GLA protein levels in the serum and plasma with minimal or no background noise, although all the methods could differentiate between the Male Fabry, E66Q, and Control groups. The Female Fabry group showed characteristic heterogeneity, which was consistent with the X-linked inheritance. This novel method is expected to be useful for the sensitive determination of GLA level in blood and elucidation of the pathogenetic basis of Fabry disease. PMID- 24236027 TI - Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific immune response. AB - Dendritic cells (DCs) play a key role in the initiation stage of an antigen specific immune response. A variety of tumor-derived factors (TDFs) can suppress DC maturation and function, resulting in defects in the tumor-specific immune response. To identify unknown TDFs that may suppress DCs maturation and function, we established a high-throughput screening technology based on a human liver tumor T7 phage cDNA library and screened all of the proteins derived from hepatoma cells that potentially interact with immature DCs. Growth/differentiation factor-15 (GDF-15) was detected and chosen for further study. By incubation of DCs cultures with GDF-15, we demonstrate that GDF-15 can inhibit surface protrusion formation during DC maturation; suppress the membrane expression of CD83, CD86 and HLA-DR on DCs; enhance phagocytosis by DCs; reduce IL-12 and elevate TGF-beta1 secretion by DCs; inhibit T cell stimulation and cytotoxic T lymphocyte (CTL) activation by DCs. By building tumor-bearing mouse models, we demonstrate that GDF-15 can inhibit the ability of DCs to stimulate a tumor-specific immune response in vivo. These results indicate that GDF-15 may be one of the critical molecules that inhibit DC maturation and function and are involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor immunotherapy. PMID- 24236028 TI - Chemical profiles of two pheromone glands are differentially regulated by distinct mating factors in honey bee queens (Apis mellifera L.). AB - Pheromones mediate social interactions among individuals in a wide variety of species, from yeast to mammals. In social insects such as honey bees, pheromone communication systems can be extraordinarily complex and serve to coordinate behaviors among many individuals. One of the primary mediators of social behavior and organization in honey bee colonies is queen pheromone, which is produced by multiple glands. The types and quantities of chemicals produced differ significantly between virgin and mated queens, and recent studies have suggested that, in newly mated queens, insemination volume or quantity can affect pheromone production. Here, we examine the long-term impact of different factors involved during queen insemination on the chemical composition of the mandibular and Dufour's glands, two of the major sources of queen pheromone. Our results demonstrate that carbon dioxide (an anesthetic used in instrumental insemination), physical manipulation of genital tract (presumably mimicking the act of copulation), insemination substance (saline vs. semen), and insemination volume (1 vs. 8 ul) all have long-term effects on mandibular gland chemical profiles. In contrast, Dufour's gland chemical profiles were changed only upon insemination and were not influenced by exposure to carbon dioxide, manipulation, insemination substance or volume. These results suggest that the chemical contents of these two glands are regulated by different neuro-physiological mechanisms. Furthermore, workers responded differently to the different mandibular gland extracts in a choice assay. Although these studies must be validated in naturally mated queens of varying mating quality, our results suggest that while the chemical composition of Dufour's gland is associated with mating status, that of the mandibular glands is associated with both mating status and insemination success. Thus, the queen appears to be signaling both status and reproductive quality to the workers, which may impact worker behavior and physiology as well as social organization and productivity of the colony. PMID- 24236029 TI - People bouncing on trampolines: dramatic energy transfer, a table-top demonstration, complex dynamics and a zero sum game. AB - Jumping on trampolines is a popular backyard recreation. In some trampoline games (e.g., "seat drop war"), when two people land on the trampoline with only a small time-lag, one person bounces much higher than the other, as if energy has been transferred from one to the other. First, we illustrate this energy-transfer in a table-top demonstration, consisting of two balls dropped onto a mini-trampoline, landing almost simultaneously, sometimes resulting in one ball bouncing much higher than the other. Next, using a simple mathematical model of two masses bouncing passively on a massless trampoline with no dissipation, we show that with specific landing conditions, it is possible to transfer all the kinetic energy of one mass to the other through the trampoline - in a single bounce. For human-like parameters, starting with equal energy, the energy transfer is maximal when one person lands approximately when the other is at the bottom of her bounce. The energy transfer persists even for very stiff surfaces. The energy conservative mathematical model exhibits complex non-periodic long-term motions. To complement this passive bouncing model, we also performed a game-theoretic analysis, appropriate when both players are acting strategically to steal the other player's energy. We consider a zero-sum game in which each player's goal is to gain the other player's kinetic energy during a single bounce, by extending her leg during flight. For high initial energy and a symmetric situation, the best strategy for both subjects (minimax strategy and Nash equilibrium) is to use the shortest available leg length and not extend their legs. On the other hand, an asymmetry in initial heights allows the player with more energy to gain even more energy in the next bounce. Thus synchronous bouncing unstable is unstable both for passive bouncing and when leg lengths are controlled as in game theoretic equilibria. PMID- 24236030 TI - Inadequate awareness among chronic kidney disease patients regarding food and drinks containing artificially added phosphate. AB - Hyperphosphatemia is an important determinant of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with CKD are advised to consume a low phosphate diet and are often prescribed phosphate-lowering drug therapy. However, commercially processed food and drinks often contain phosphate compounds, but the phosphate level is not usually provided in the ingredient list, which makes it difficult for CKD patients to choose a correct diet. We conducted a survey of the awareness of food/beverages containing artificially added phosphate among CKD patients undergoing hemodialysis. The subjects were 153 patients (77 males and 76 females; average age 56+/-11 years) who were randomly selected from the Dialysis Center of Hirosaki City, Japan. The subjects were provided with a list of questions. The survey results showed that 93% of the subjects were aware of the presence of high sugar content in soda, whereas only 25% were aware of the presence of phosphate (phosphoric acid) in such drinks. Despite 78% of the subjects being aware of the detrimental effects of consumption of a high phosphate diet, 43% drank at least 1 to 5 cans of soda per week and about 17% consumed "fast food" once each week. We also assessed the immediate effects of high-phosphate containing carbonated soda consumption by determining urinary calcium, phosphate, protein and sugar contents in overnight fasted healthy volunteers (n = 55; average age 20.7+/-0.3 years old, 20 males and 35 females). Significantly higher urinary calcium (adjusted using urinary creatinine) excretion was found 2 h after consuming 350 ml of carbonated soda compared to the fasting baseline level (0.15+/-0.01 vs. 0.09+/-0.01, p = 0.001). Our survey results suggest that CKD patients undergoing hemodialysis are not adequately aware of the hidden source of phosphate in their diet, and emphasize the need for educational initiatives to raise awareness of this issue among CKD patients. PMID- 24236031 TI - 2A and the auxin-based degron system facilitate control of protein levels in Plasmodium falciparum. AB - Analysis of gene function in Plasmodium falciparum, the most important human malaria parasite, is restricted by the lack of robust and simple reverse genetic tools. Approaches to manipulate protein levels post-translationally are powerful tools to study protein-off effects especially in the haploid malaria parasite where genetic knockouts of essential genes are lethal. We investigated if the auxin-inducible degron system is functional in P. falciparum and found that degron-tagged yellow fluorescent protein levels were efficiently reduced upon addition of auxin which otherwise had no effect on parasite viability. The genetic components required in this conditional approach were co-expressed in P. falciparum by applying the small peptide 2A. 2A is a self-processing peptide from Foot-And-Mouth Disease virus that allows the whole conditional system to be accommodated on a single plasmid vector and ensures stoichiometric expression levels. PMID- 24236032 TI - A DeltaclpB mutant of Francisella tularensis subspecies holarctica strain, FSC200, is a more effective live vaccine than F. tularensis LVS in a mouse respiratory challenge model of tularemia. AB - Francisella tularensis subsp. tularensis is a highly virulent pathogen for humans especially if inhaled. Consequently, it is considered to be a potential biothreat agent. An experimental vaccine, F. tularensis live vaccine strain, derived from the less virulent subsp. holarctica, was developed more than 50 years ago, but remains unlicensed. Previously, we developed a novel live vaccine strain, by deleting the chaperonin clpB gene from F. tularensis subsp. tularensis strain, SCHU S4. SCHU S4DeltaclpB was less virulent for mice than LVS and a more effective vaccine against respiratory challenge with wild type SCHU S4. In the current study, we were interested to determine whether a similar mutant on the less virulent subsp. holarctica background would also outperform LVS in terms of safety and efficacy. To this end, clpB was deleted from clinical holarctica strain, FSC200. FSC200DeltaclpB had a significantly higher intranasal LD50 than LVS for BALB/c mice, but replicated to higher numbers at foci of infection after dermal inoculation. Moreover, FSC200DeltaclpB killed SCID mice more rapidly than LVS. However, dermal vaccination of BALB/c mice with the former versus the latter induced greater protection against respiratory challenge with SCHU S4. This increased efficacy was associated with enhanced production of pulmonary IL-17 after SCHU S4 challenge. PMID- 24236033 TI - Clinical and socio-demographic characteristics of college students exposed to traumatic experiences: a census of seven college institutions in Northeastern Brazil. AB - BACKGROUND: Epidemiological studies show that most of the adult population will be exposed to at least one potentially traumatic event in the course of his/her life; adolescence and early adulthood are the most vulnerable periods of life for exposure to traumatic experiences (70% of their deaths are due to external causes). Posttraumatic Stress Disorder is characterized by the development of dysfunctional symptoms that cause distress or social, academic, or occupational impairment, as result of exposure to a traumatic event. The aim of this multicentric study is to establish the proportion of college students, within seven institutions in Northeastern Brazil, who were exposed to traumatic experience and met PTSD criteria. METHODS/DESIGN: A one-phase census protocol of seven college institutions in three metropolitan regions in Northeastern Brazil was performed (April to July 2011). All students aged 18 years or older, matriculated and attending their first or final semester were eligible. The self applied protocol consisted of a socio-demographic questionnaire and the following scales adjusted to Brazilian Portuguese standards Trauma History Questionnaire (THQ), PTSD Checklist-Civilian (PCL-C), Impulsivity Scale (BIS-11). Data were entered into SPSS 17.0. RESULTS: 2213 (85.5%) students consented to participate, and completely filled in the protocols. Of these, 66.1% were woman, mean age 23.9 (SD 6.3), 82.7% were single, and 57.3% attended university outside their native cities. The total PTSD prevalence was 14%, and the median for frequency of trauma exposure was 5 events. CONCLUSION: A high frequency of exposure to violence, as well as a high rate of PTSD, suicide attempts, and high-risk sexual behavior was found in Brazilian college students. This highlights the importance of effective public health actions in relation to the prevention and treatment of PTSD and other dysfunctional behaviors resulting from traumatic exposure in young individuals, usually an at risk population for violence and traumatic situations. PMID- 24236034 TI - Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALENTM. AB - Xeroderma pigmentosum group C (XP-C) is a rare human syndrome characterized by hypersensitivity to UV light and a dramatic predisposition to skin neoplasms. XP C cells are deficient in the nucleotide excision repair (NER) pathway, a complex process involved in the recognition and removal of DNA lesions. Several XPC mutations have been described, including a founder mutation in North African patients involving the deletion of a TG dinucleotide (DeltaTG) located in the middle of exon 9. This deletion leads to the expression of an inactive truncated XPC protein, normally involved in the first step of NER. New approaches used for gene correction are based on the ability of engineered nucleases such as Meganucleases, Zinc-Finger nucleases or TALE nucleases to accurately generate a double strand break at a specific locus and promote correction by homologous recombination through the insertion of an exogenous DNA repair matrix. Here, we describe the targeted correction of the DeltaTG mutation in XP-C cells using engineered meganuclease and TALENTM. The methylated status of the XPC locus, known to inhibit both of these nuclease activities, led us to adapt our experimental design to optimize their in vivo efficacies. We show that demethylating treatment as well as the use of TALENTM insensitive to CpG methylation enable successful correction of the DeltaTG mutation. Such genetic correction leads to re-expression of the full-length XPC protein and to the recovery of NER capacity, attested by UV-C resistance of the corrected cells. Overall, we demonstrate that nuclease-based targeted approaches offer reliable and efficient strategies for gene correction. PMID- 24236035 TI - Vitis phylogenomics: hybridization intensities from a SNP array outperform genotype calls. AB - Understanding relationships among species is a fundamental goal of evolutionary biology. Single nucleotide polymorphisms (SNPs) identified through next generation sequencing and related technologies enable phylogeny reconstruction by providing unprecedented numbers of characters for analysis. One approach to SNP based phylogeny reconstruction is to identify SNPs in a subset of individuals, and then to compile SNPs on an array that can be used to genotype additional samples at hundreds or thousands of sites simultaneously. Although powerful and efficient, this method is subject to ascertainment bias because applying variation discovered in a representative subset to a larger sample favors identification of SNPs with high minor allele frequencies and introduces bias against rare alleles. Here, we demonstrate that the use of hybridization intensity data, rather than genotype calls, reduces the effects of ascertainment bias. Whereas traditional SNP calls assess known variants based on diversity housed in the discovery panel, hybridization intensity data survey variation in the broader sample pool, regardless of whether those variants are present in the initial SNP discovery process. We apply SNP genotype and hybridization intensity data derived from the Vitis9kSNP array developed for grape to show the effects of ascertainment bias and to reconstruct evolutionary relationships among Vitis species. We demonstrate that phylogenies constructed using hybridization intensities suffer less from the distorting effects of ascertainment bias, and are thus more accurate than phylogenies based on genotype calls. Moreover, we reconstruct the phylogeny of the genus Vitis using hybridization data, show that North American subgenus Vitis species are monophyletic, and resolve several previously poorly known relationships among North American species. This study builds on earlier work that applied the Vitis9kSNP array to evolutionary questions within Vitis vinifera and has general implications for addressing ascertainment bias in array-enabled phylogeny reconstruction. PMID- 24236036 TI - Molecular dynamics analysis of a novel beta3 Pro189Ser mutation in a patient with glanzmann thrombasthenia differentially affecting alphaIIbbeta3 and alphavbeta3 expression. AB - Mutations in ITGA2B and ITGB3 cause Glanzmann thrombasthenia, an inherited bleeding disorder in which platelets fail to aggregate when stimulated. Whereas an absence of expression or qualitative defects of alphaIIbbeta3 mainly affect platelets and megakaryocytes, alphavbeta3 has a widespread tissue distribution. Little is known of how amino acid substitutions of beta3 comparatively affect the expression and structure of both integrins. We now report computer modelling including molecular dynamics simulations of extracellular head domains of alphaIIbbeta3 and alphavbeta3 to determine the role of a novel beta3 Pro189Ser (P163S in the mature protein) substitution that abrogates alphaIIbbeta3 expression in platelets while allowing synthesis of alphavbeta3. Transfection of wild-type and mutated integrins in CHO cells confirmed that only alphavbeta3 surface expression was maintained. Modeling initially confirmed that replacement of alphaIIb by alphav in the dimer results in a significant decrease in surface contacts at the subunit interface. For alphaIIbbeta3, the presence of beta3S163 specifically displaces an alpha-helix starting at position 259 and interacting with beta3R261 while there is a moderate 11% increase in intra-subunit H-bonds and a very weak decrease in the global H-bond network. In contrast, for alphavbeta3, S163 has different effects with beta3R261 coming deeper into the propeller with a 43% increase in intra-subunit H-bonds but with little effect on the global H-bond network. Compared to the WT integrins, the P163S mutation induces a small increase in the inter-subunit fluctuations for alphaIIbbeta3 but a more rigid structure for alphavbeta3. Overall, this mutation stabilizes alphavbeta3 despite preventing alphaIIbbeta3 expression. PMID- 24236037 TI - Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. AB - Human and animal studies strongly suggest that dietary gluten could play a causal role in the etiopathogenesis of type 1 diabetes (T1D). However, the mechanisms have not been elucidated. Recent reports indicate that the intestinal microbiome has a major influence on the incidence of T1D. Since diet is known to shape the composition of the intestinal microbiome, we investigated using non-obese diabetic (NOD) mice whether changes in the intestinal microbiome could be attributed to the pro- and anti-diabetogenic effects of gluten-containing and gluten-free diets, respectively. NOD mice were raised on gluten-containing chows (GCC) or gluten-free chows (GFC). The incidence of diabetes was determined by monitoring blood glucose levels biweekly using a glucometer. Intestinal microbiome composition was analyzed by sequencing 16S rRNA amplicons derived from fecal samples. First of all, GCC-fed NOD mice had the expected high incidence of hyperglycemia whereas NOD mice fed with a GFC had significantly reduced incidence of hyperglycemia. Secondly, when the fecal microbiomes were compared, Bifidobacterium, Tannerella, and Barnesiella species were increased (p = 0.03, 0.02, and 0.02, respectively) in the microbiome of GCC mice, where as Akkermansia species was increased (p = 0.02) in the intestinal microbiomes of NOD mice fed GFC. Thirdly, both of the gluten-free chows that were evaluated, either egg white based (EW-GFC) or casein based (C-GFC), significantly reduced the incidence of hyperglycemia. Interestingly, the gut microbiome from EW-GFC mice was similar to C-GFC mice. Finally, adding back gluten to the gluten-free diet reversed its anti diabetogenic effect, reduced Akkermansia species and increased Bifidobacterium, Tannerella, and Barnesiella suggesting that the presence of gluten is directly responsible for the pro-diabetogenic effects of diets and it determines the gut microflora. Our novel study thus suggests that dietary gluten could modulate the incidence of T1D by changing the gut microbiome. PMID- 24236038 TI - Associations between physical and cognitive doping--a cross-sectional study in 2.997 triathletes. AB - PURPOSE: This study assessed, for the first time, prevalence estimates for physical and cognitive doping within a single collective of athletes using the randomized response technique (RRT). Furthermore, associations between the use of legal and freely available substances to improve physical and cognitive performance (enhancement) and illicit or banned substances to improve physical and cognitive performance (doping) were examined. METHODS: An anonymous questionnaire using the unrelated question RRT was used to survey 2,997 recreational triathletes in three sports events (Frankfurt, Regensburg, and Wiesbaden) in Germany. Prior to the survey, statistical power analyses were performed to determine sample size. Logistic regression was used to predict physical and cognitive enhancement and the bootstrap method was used to evaluate differences between the estimated prevalences of physical and cognitive doping. RESULTS: 2,987 questionnaires were returned (99.7%). 12-month prevalences for physical and cognitive doping were 13.0% and 15.1%, respectively. The prevalence estimate for physical doping was significantly higher in athletes who also used physical enhancers, as well as in athletes who took part in the European Championship in Frankfurt compared to those who did not. The prevalence estimate for cognitive doping was significantly higher in athletes who also used physical and cognitive enhancers. Moreover, the use of physical and cognitive enhancers were significantly associated and also the use of physical and cognitive doping. DISCUSSION: The use of substances to improve physical and cognitive performance was associated on both levels of legality (enhancement vs. doping) suggesting that athletes do not use substances for a specific goal but may have a general propensity to enhance. This finding is important for understanding why people use such substances. Consequently, more effective prevention programs against substance abuse and doping could be developed. PMID- 24236039 TI - Analysis of the Protein phosphotome of Entamoeba histolytica reveals an intricate phosphorylation network. AB - Phosphorylation is the most common mechanism for the propagation of intracellular signals. Protein phosphatases and protein kinases play a dynamic antagonistic role in protein phosphorylation. Protein phosphatases make up a significant fraction of eukaryotic proteome. In this article, we report the identification and analysis of protein phosphatases in the intracellular parasite Entamoeba histolytica. Based on an in silico analysis, we classified 250 non-redundant protein phosphatases in E. histolytica. The phosphotome of E. histolytica is 3.1% of its proteome and 1.3 times of the human phosphotome. In this extensive study, we identified 42 new putative phosphatases (39 hypothetical proteins and 3 pseudophosphatases). The presence of pseudophosphatases may have an important role in virulence of E. histolytica. A comprehensive phosphotome analysis of E. histolytica shows spectacular low similarity to human phosphatases, making them potent candidates for drug target. PMID- 24236040 TI - Nitric oxide regulates neuronal activity via calcium-activated potassium channels. AB - Nitric oxide (NO) is an unconventional membrane-permeable messenger molecule that has been shown to play various roles in the nervous system. How NO modulates ion channels to affect neuronal functions is not well understood. In gastropods, NO has been implicated in regulating the feeding motor program. The buccal motoneuron, B19, of the freshwater pond snail Helisoma trivolvis is active during the hyper-retraction phase of the feeding motor program and is located in the vicinity of NO-producing neurons in the buccal ganglion. Here, we asked whether B19 neurons might serve as direct targets of NO signaling. Previous work established NO as a key regulator of growth cone motility and neuronal excitability in another buccal neuron involved in feeding, the B5 neuron. This raised the question whether NO might modulate the electrical activity and neuronal excitability of B19 neurons as well, and if so whether NO acted on the same or a different set of ion channels in both neurons. To study specific responses of NO on B19 neurons and to eliminate indirect effects contributed by other cells, the majority of experiments were performed on single cultured B19 neurons. Addition of NO donors caused a prolonged depolarization of the membrane potential and an increase in neuronal excitability. The effects of NO could mainly be attributed to the inhibition of two types of calcium-activated potassium channels, apamin-sensitive and iberiotoxin-sensitive potassium channels. NO was found to also cause a depolarization in B19 neurons in situ, but only after NO synthase activity in buccal ganglia had been blocked. The results suggest that NO acts as a critical modulator of neuronal excitability in B19 neurons, and that calcium-activated potassium channels may serve as a common target of NO in neurons. PMID- 24236041 TI - Clinical significance of sIL-2R levels in B-cell lymphomas. AB - Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R alpha chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas. PMID- 24236042 TI - The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models. AB - Clinical evidence suggests that individuals with factor VIII (FVIII) deficiency (hemophilia A) are protected against venous thrombosis, but treatment with recombinant proteins can increase their risk for thrombosis. In this study we examined the dynamics of thrombus formation in individuals with hemophilia A and their response to replacement and bypass therapies under venous flow conditions. Fibrin and platelet accumulation were measured in microfluidic flow assays on a TF-rich surface at a shear rate of 100 s-1. Thrombin generation was calculated with a computational spatial-temporal model of thrombus formation. Mild FVIII deficiencies (5-30% normal levels) could support fibrin fiber formation, while severe (<1%) and moderate (1-5%) deficiencies could not. Based on these experimental observations, computational calculations estimate an average thrombin concentration of ~10 nM is necessary to support fibrin formation under flow. There was no difference in fibrin formation between severe and moderate deficiencies, but platelet aggregate size was significantly larger for moderate deficiencies. Computational calculations estimate that the local thrombin concentration in moderate deficiencies is high enough to induce platelet activation (>1 nM), but too low to support fibrin formation (<10 nM). In the absence of platelets, fibrin formation was not supported even at normal FVIII levels, suggesting platelet adhesion is necessary for fibrin formation. Individuals treated by replacement therapy, recombinant FVIII, showed normalized fibrin formation. Individuals treated with bypass therapy, recombinant FVIIa, had a reduced lag time in fibrin formation, as well as elevated fibrin accumulation compared to healthy controls. Treatment of rFVIIa, but not rFVIII, resulted in significant changes in fibrin dynamics that could lead to a prothrombotic state. PMID- 24236043 TI - Neural correlates of four broad temperament dimensions: testing predictions for a novel construct of personality. AB - Four suites of behavioral traits have been associated with four broad neural systems: the 1) dopamine and related norepinephrine system; 2) serotonin; 3) testosterone; 4) and estrogen and oxytocin system. A 56-item questionnaire, the Fisher Temperament Inventory (FTI), was developed to define four temperament dimensions associated with these behavioral traits and neural systems. The questionnaire has been used to suggest romantic partner compatibility. The dimensions were named: Curious/Energetic; Cautious/Social Norm Compliant; Analytical/Tough-minded; and Prosocial/Empathetic. For the present study, the FTI was administered to participants in two functional magnetic resonance imaging studies that elicited feelings of love and attachment, near-universal human experiences. Scores for the Curious/Energetic dimension co-varied with activation in a region of the substantia nigra, consistent with the prediction that this dimension reflects activity in the dopamine system. Scores for the Cautious/Social Norm Compliant dimension correlated with activation in the ventrolateral prefrontal cortex in regions associated with social norm compliance, a trait linked with the serotonin system. Scores on the Analytical/Tough-minded scale co-varied with activity in regions of the occipital and parietal cortices associated with visual acuity and mathematical thinking, traits linked with testosterone. Also, testosterone contributes to brain architecture in these areas. Scores on the Prosocial/Empathetic scale correlated with activity in regions of the inferior frontal gyrus, anterior insula and fusiform gyrus. These are regions associated with mirror neurons or empathy, a trait linked with the estrogen/oxytocin system, and where estrogen contributes to brain architecture. These findings, replicated across two studies, suggest that the FTI measures influences of four broad neural systems, and that these temperament dimensions and neural systems could constitute foundational mechanisms in personality structure and play a role in romantic partnerships. PMID- 24236044 TI - Arx polyalanine expansion in mice leads to reduced pancreatic alpha-cell specification and increased alpha-cell death. AB - ARX/Arx is a homeodomain-containing transcription factor necessary for the specification and early maintenance of pancreatic endocrine alpha-cells. Many transcription factors important to pancreas development, including ARX/Arx, are also crucial for proper brain development. Although null mutations of ARX in human patients result in the severe neurologic syndrome XLAG (X-linked lissencephaly associated with abnormal genitalia), the most common mutation is the expansion of the first polyalanine tract of ARX, which results primarily in the clinical syndrome ISSX (infantile spasms). Mouse models of XLAG, ISSX and other human ARX mutations demonstrate a direct genotype-phenotype correlation in ARX-related neurologic disorders. Furthermore, mouse models utilizing a polyalanine tract expansion mutation have illustrated critical developmental differences between null mutations and expansion mutations in the brain, revealing context-specific defects. Although Arx is known to be required for the specification and early maintenance of pancreatic glucagon-producing alpha-cells, the consequences of the Arx polyalanine expansion on pancreas development remain unknown. Here we report that mice with an expansion mutation in the first polyalanine tract of Arx exhibit impaired alpha-cell specification and maintenance, with gradual alpha-cell loss due to apoptosis. This is in contrast to the re-specification of alpha-cells into beta- and delta-cells that occurs in mice null for Arx. Overall, our analysis of an Arx polyalanine expansion mutation on pancreatic development suggests that impaired alpha-cell function might also occur in ISSX patients. PMID- 24236045 TI - Diversity and evolution of bacterial twin arginine translocase protein, TatC, reveals a protein secretion system that is evolving to fit its environmental niche. AB - BACKGROUND: The twin-arginine translocation (Tat) protein export system enables the transport of fully folded proteins across a membrane. This system is composed of two integral membrane proteins belonging to TatA and TatC protein families and in some systems a third component, TatB, a homolog of TatA. TatC participates in substrate protein recognition through its interaction with a twin arginine leader peptide sequence. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to explore TatC diversity, evolution and sequence conservation in bacteria to identify how TatC is evolving and diversifying in various bacterial phyla. Surveying bacterial genomes revealed that 77% of all species possess one or more tatC loci and half of these classes possessed only tatC and tatA genes. Phylogenetic analysis of diverse TatC homologues showed that they were primarily inherited but identified a small subset of taxonomically unrelated bacteria that exhibited evidence supporting lateral gene transfer within an ecological niche. Examination of bacilli tatCd/tatCy isoform operons identified a number of known and potentially new Tat substrate genes based on their frequent association to tatC loci. Evolutionary analysis of these Bacilli isoforms determined that TatCy was the progenitor of TatCd. A bacterial TatC consensus sequence was determined and highlighted conserved and variable regions within a three dimensional model of the Escherichia coli TatC protein. Comparative analysis between the TatC consensus sequence and Bacilli TatCd/y isoform consensus sequences revealed unique sites that may contribute to isoform substrate specificity or make TatA specific contacts. Synonymous to non-synonymous nucleotide substitution analyses of bacterial tatC homologues determined that tatC sequence variation differs dramatically between various classes and suggests TatC specialization in these species. CONCLUSIONS/SIGNIFICANCE: TatC proteins appear to be diversifying within particular bacterial classes and its specialization may be driven by the substrates it transports and the environment of its host. PMID- 24236046 TI - An ultrasensitive high throughput screen for DNA methyltransferase 1-targeted molecular probes. AB - DNA methyltransferase 1 (DNMT1) is the enzyme most responsible for epigenetic modification of human DNA and the intended target of approved cancer drugs such as 5-aza-cytidine and 5-aza-2'-deoxycytidine. 5-aza nucleosides have complex mechanisms of action that require incorporation into DNA, and covalent trapping and proteolysis of DNMT isozymes. Direct DNMT inhibitors are needed to refine understanding of the role of specific DNMT isozymes in cancer etiology and, potentially, to improve cancer prevention and treatment. Here, we developed a high throughput pipeline for identification of direct DNMT1 inhibitors. The components of this screen include an activated form of DNMT1, a restriction enzyme-coupled fluorigenic assay performed in 384 well plates with a z-factor of 0.66, a counter screen against the restriction enzyme, a screen to eliminate DNA intercalators, and a differential scanning fluorimetry assay to validate direct binders. Using the Microsource Spectrum collection of 2320 compounds, this screen identified nine compounds with dose responses ranging from 300 nM to 11 uM, representing at least two different pharmacophores with DNMT1 inhibitory activity. Seven of nine inhibitors identified exhibited two to four-fold selectivity for DNMT1 versus DNMT3A. PMID- 24236047 TI - Zinc Finger 280B regulates sGCalpha1 and p53 in prostate cancer cells. AB - The Zinc Finger (ZNF) 280B protein was identified as an unexpected target of an shRNA designed for sGCalpha1. Further analysis showed that these two proteins are connected in another way, with 280B up-regulation of sGCalpha1 expression. Knock down and over-expression experiments showed that 280B serves pro-growth and pro survival functions in prostate cancer. Surprisingly however, these pro-cancer functions of 280B are not mediated by sGCalpha1, which itself has similar functions in prostate cancer, but by down-regulated p53. The p53 protein is a second target of 280B in prostate cancer, but unlike sGCalpha1, p53 is down regulated by 280B. 280B induces p53 nuclear export, leading to subsequent proteasomal degradation. The protein responsible for p53 regulation by 280B is Mdm2, the E3 ubiquitin ligase that promotes p53 degradation by inducing its nuclear export. We show here that 280B up-regulates expression of Mdm2 in prostate cancer cells, and this regulation is via the Mdm2 promoter. To demonstrate an in vivo relevance to this interaction, expression studies show that 280B protein levels are up-regulated in prostate cancer and these levels correspond to reduced levels of p53. Thus, by enhancing the expression of Mdm2, the uncharacterized 280B protein provides a novel mechanism of p53 suppression in prostate cancer. PMID- 24236048 TI - Enhancement of tight junctional barrier function by micronutrients: compound specific effects on permeability and claudin composition. AB - Amid an increasing number of reports in the literature concerning epithelial barrier enhancement by various nutrient compounds, there has never been a study performing side-by-side comparisons of these agents in a single epithelial model. We compare five nutrient compounds (previously reported in various epithelial models to enhance barrier function) regarding their ability to increase transepithelial electrical resistance (R(t)) and decrease transepithelial mannitol permeability (J(m)) across LLC-PK1 renal epithelial cell layers. The effects of these nutrients on the abundance of various tight junctional proteins are also compared. In the overall group of nutrients tested--zinc, indole, quercetin, butyrate and nicotine--only nicotine failed to improve barrier function by either parameter. Nicotine also was without effect on tight junctional proteins. Quercetin simultaneously increased R(t) and decreased J(m). Zinc, butyrate and indole only exhibited statistically significant enhancement of R(t). Each of these four effective nutrient compounds had unique patterns of effects on the panel of tight junctional proteins studied. No two compounds produced the same pattern of effects. This unique pattern of effects on tight junctional complex composition by each compound establishes the chance for additive or even synergistic improvement of barrier function by combinations of compounds. A synergistic effect of the combination of quercetin and zinc on R(t) is shown. PMID- 24236049 TI - High flow conditions increase connexin43 expression in a rat arteriovenous and angioinductive loop model. AB - Gap junctions are involved in vascular growth and their expression pattern is modulated in response to hemodynamic conditions. They are clusters of intercellular channels formed by connexins (Cx) of which four subtypes are expressed in the cardiovascular system, namely Cx37, Cx40, Cx43 and Cx45. We hypothesize that high flow conditions affect vascular expression of Cx in vivo. To test this hypothesis, flow hemodynamics and subsequent changes in vascular expression of Cx were studied in an angioinductive rat arteriovenous (AV) loop model. Fifteen days after interposition of a femoral vein graft between femoral artery and vein encased in a fibrin-filled chamber strong neovascularization was evident that emerged predominantly from the graft. Blood flow through the grafted vessel was enhanced ~4.5-fold accompanied by increased pulsatility exceeding arterial levels. Whereas Cx43 protein expression in the femoral vein is negligible at physiologic flow conditions as judged by immunostaining its expression was enhanced in the endothelium of the venous graft exposed to these hemodynamic changes for 5 days. This was most likely due to enhanced transcription since Cx43 mRNA increased likewise, whereas Cx37 mRNA expression remained unaffected and Cx40 mRNA was reduced. Although enhanced Cx43 expression in regions of high flow in vivo has already been demonstrated, the arteriovenous graft used in the present study provides a reliable model to verify an association between Cx43 expression and high flow conditions in vivo that was selective for this Cx. We conclude that enhancement of blood flow and its oscillation possibly associated with the transition from laminar to more turbulent flow induces Cx43 expression in a vein serving as an AV loop. It is tempting to speculate that this upregulation is involved in the vessel formation occuring in this model as Cx43 was suggested to be involved in angiogenesis. PMID- 24236050 TI - Overexpression of EFEMP1 correlates with tumor progression and poor prognosis in human ovarian carcinoma. AB - OBJECTIVE: This study was to explore the role of EFEMP1 in ovarian tumor progression and its relationship with prognosis of ovarian carcinoma. METHODS: EFEMP1 mRNA and protein expressions in normal ovarian tissue, ovarian tumor, high invasive subclones and low invasive subclones were evaluated by immunohistochemistry and real time RT-PCR. Serum EFEMP1 levels in patients with ovarian tumor were measured by ELISA assay. To assess the angiogenic properties of EFEMP1, VEGF and tumor microvessel density were analyzed in ovarian carcinoma by immunohistochemistry. RESULTS: EFEMP1 expression was up-regulated in ovarian carcinoma, positively correlated with MVD and VEGF, and its overexpression and high serum levels were significantly associated with high stage, low differentiation, lymph node metastasis and poor prognosis of ovarian cancer. EFEMP1 expression was also found to be over-expressed in the highly invasive subclones compared with the low invasive subclones. CONCLUSION: EFEMP1 is a newly identified gene over-expressed in ovarian cancer, associated with poor clinicopathologic features and promotes angiogenesis. This study shows that EFEMP1 may serve as a new prognostic factor and a therapeutic target for patients with ovarian cancer in the future. PMID- 24236051 TI - Identification and developmental profiling of microRNAs in diamondback moth, Plutellaxylostella (L.). AB - MicroRNAs (miRNAs) are a group of small RNAs involved in various biological processes through negative regulation of mRNAs at the post-transcriptional level. Although miRNA profiles have been documented in over two dozen insect species, few are agricultural pests. In this study, both conserved and novel miRNAs in the diamondback moth, Plutella xylostella L., a devastating insect pest of cruciferous crops worldwide, were documented. High-throughput sequencing of a small RNA library constructed from a mixed life stages of P. xylostella, including eggs, 1st to 4th (last) instar larvae, pupae and adults, identified 384 miRNAs, of which 174 were P. xylostella specific. In addition, temporal expressions of 234 miRNAs at various developmental stages were investigated using a customized microarray analysis. Among the 91 differentially expressed miRNAs, qRT-PCR analysis was used to validate highly expressed miRNAs at each stage. The combined results not only systematically document miRNA profiles in an agriculturally important insect pest, but also provide molecular targets for future functional analysis and, ultimately, genetic-based pest control practice. PMID- 24236052 TI - MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9. AB - The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors. The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r2 = 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown. PMID- 24236053 TI - Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears. AB - Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA. PMID- 24236054 TI - Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial. AB - BACKGROUND: Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. METHODS AND FINDINGS: Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. CONCLUSIONS: In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation. PMID- 24236055 TI - Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. AB - Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation. PMID- 24236056 TI - HER2 phosphorylates and destabilizes pro-apoptotic PUMA, leading to antagonized apoptosis in cancer cells. AB - HER2 is overexpressed in 15-20% of breast cancers. HER2 overexpression is known to reduce apoptosis but the underlying mechanisms for this association remain unclear. To elucidate the mechanisms for HER2-mediated survival, we investigated the relationship between HER2 and p53 upregulated modulator of apoptosis (PUMA), a potent apoptosis inducer. Our results showed that HER2 interacts with PUMA, which was independent of HER2 activation. In addition, we observed that HER2 interacted with PUMA in both mitochondrial and non-mitochondrial compartments. We next examined whether HER2 phosphorylates PUMA. Notably, PUMA tyrosine phosphorylation has never been reported. Using an intracellular assay, we found PUMA to be phosphorylated in breast cancer cells with activated HER2. Via cell free HER2 kinase assay, we observed that PUMA was directly phosphorylated by HER2. Activation of HER2 decreased PUMA protein half-life. To identify which of the three tyrosines within PUMA are targeted by HER2, we generated three PUMA non phosphorylation mutants each with a single Tyr->Phe substitution. Results indicated that each PUMA single mutant had lost some, but not all phosphorylation by HER2 indicating that HER2 targets all three tyrosines. Consequently, we created an additional PUMA mutant with all three tyrosines mutated (TM-PUMA) that could not be phosphorylated by HER2. Importantly, TM-PUMA was found to have a longer half-life than PUMA. An inverse association was observed between HER2 and PUMA in 93 invasive breast carcinoma samples. We further found that TM-PUMA suppressed growth of breast cancer cells to a greater degree than PUMA. Also, TM PUMA had a stronger propensity to induce apoptosis than PUMA. Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein. The HER2-PUMA interplay represents a novel mechanism by which PUMA is regulated and a new molecular basis for HER2-mediated growth and survival of cancer cells. PMID- 24236057 TI - Correlates of adult binge drinking: evidence from a British cohort. AB - OBJECTIVE: To investigate whether parental social class and cognitive ability in childhood, as well as social and psychological factors, particularly personality traits, are independently associated with binge drinking in 50 year old adults assessed in a longitudinal birth cohort study. METHOD: 17,415 babies born in Great Britain in 1958 and followed up at 11, 33, and 50 years of age. Their binge drinking alcohol abuse at aged 50 was the outcome measure. RESULTS: 6,478 participants with data on parental social class, childhood cognitive ability, educational qualifications at age 33, personality traits, psychological distress, occupational levels, and alcohol consumption (all measured at age 50) were included in the study. Using logistic regression analyses, results showed that parental social class, childhood intelligence, educational qualifications, occupational levels, personality traits (Extraversion and Disagreeableness), as well as psychological distress, were all significantly and independently associated with adult excessive alcohol use. Men tended to binge drink more than women (22% in men and 9.8% in women). CONCLUSION: Both social and psychological factors influence adult excessive alcohol consumption. Personality traits play a more important role than previously understood. There appears to be a distinction between the frequency and dose level of alcohol consumption. PMID- 24236058 TI - Efficient method of genotyping ob/ob mice using high resolution melting analysis. AB - OBJECTIVE: Direct health care costs of obesity continue to grow throughout the world and research on obesity disease models are on the rise. The ob/ob mouse is a well-characterized model of obesity and associated risk factors. Successful breeding and backcrossing onto different backgrounds are essential to create knockout models. Ob/ob mice are sterile and heterozygotes must be identified by genotyping to maintain breeding colonies. Several methods are employed to detect the ob mutant allele, a single nucleotide polymorphism (SNP). Gel based methods are time consuming and inconsistent, and non-gel based assays rely upon expensive and complex reagents or instruments. A fast, high-throughput, cost effective, and consistent method to identify Lep(ob) mutation is much needed. DESIGN AND METHODS: Primers to produce an amplicon for High Resolution Melting Analysis (HRM) of the Lep(ob) SNP were designed and validated. RESULTS: Fluorescence normalized high resolution melting curve plots delineated ob/+, ob/ob, and WT genotypes. Genotypes were also confirmed phenotypically. CONCLUSIONS: HRM of the Lep(ob) SNP allows closed-tube identification of the Lep(ob) mutation using a real-time PCR machine now common to most labs/departments. Advantages of this method include assay sensitivity/accuracy, low cost dyes, less optimization, and cost effectiveness as compared to other genotyping techniques. PMID- 24236059 TI - Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels. AB - Low oxygen tension (hypoxia) contributes critically to pluripotency of human embryonic stem cells (hESCs) by preventing spontaneous differentiation and supporting self-renewal. However, it is not well understood how hESCs respond to reduced oxygen availability and what are the molecular mechanisms maintaining pluripotency in these conditions. In this study we characterized the transcriptional and molecular responses of three hESC lines (H9, HS401 and HS360) on short (2 hours), intermediate (24 hours) and prolonged (7 days) exposure to low oxygen conditions (4% O2). In response to prolonged hypoxia the expression of pluripotency surface marker SSEA-3 was increased. Furthermore, the genome wide gene-expression analysis revealed that a substantial proportion (12%) of all hypoxia-regulated genes in hESCs, were directly linked to the mechanisms controlling pluripotency or differentiation. Moreover, transcription of MYC oncogene was induced in response to continuous hypoxia. At the protein level MYC was stabilized through phosphorylation already in response to a short hypoxic exposure. Total MYC protein levels remained elevated throughout all the time points studied. Further, MYC protein expression in hypoxia was affected by silencing HIF2alpha, but not HIF1alpha. Since MYC has a crucial role in regulating pluripotency we propose that induction of sustained MYC expression in hypoxia contributes to activation of transcriptional programs critical for hESC self-renewal and maintenance of enhanced pluripotent state. PMID- 24236060 TI - Alcohol abuse promotes changes in non-synaptic epileptiform activity with concomitant expression changes in cotransporters and glial cells. AB - Non-synaptic mechanisms are being considered the common factor of brain damage in status epilepticus and alcohol intoxication. The present work reports the influence of the chronic use of ethanol on epileptic processes sustained by non synaptic mechanisms. Adult male Wistar rats administered with ethanol (1, 2 e 3 g/kg/d) during 28 days were compared with Control. Non-synaptic epileptiform activities (NEAs) were induced by means of the zero-calcium and high-potassium model using hippocampal slices. The observed involvement of the dentate gyrus (DG) on the neurodegeneration promoted by ethanol motivated the monitoring of the electrophysiological activity in this region. The DG regions were analyzed for the presence of NKCC1, KCC2, GFAP and CD11b immunoreactivity and cell density. The treated groups showed extracellular potential measured at the granular layer with increased DC shift and population spikes (PS), which was remarkable for the group E1. The latencies to the NEAs onset were more prominent also for the treated groups, being correlated with the neuronal loss. In line with these findings were the predispositions of the treated slices for neuronal edema after NEAs induction, suggesting that restrict inter-cell space counteracts the neuronal loss and subsists the hyper-synchronism. The significant increase of the expressions of NKCC1 and CD11b for the treated groups confirms the existence of conditions favorable to the observed edematous necrosis. The data suggest that the ethanol consumption promotes changes on the non-synaptic mechanisms modulating the NEAs. For the lower ethanol dosage the neurophysiological changes were more effective suggesting to be due to the less intense neurodegenertation. PMID- 24236061 TI - The phylogeny of Little Red Riding Hood. AB - Researchers have long been fascinated by the strong continuities evident in the oral traditions associated with different cultures. According to the 'historic geographic' school, it is possible to classify similar tales into "international types" and trace them back to their original archetypes. However, critics argue that folktale traditions are fundamentally fluid, and that most international types are artificial constructs. Here, these issues are addressed using phylogenetic methods that were originally developed to reconstruct evolutionary relationships among biological species, and which have been recently applied to a range of cultural phenomena. The study focuses on one of the most debated international types in the literature: ATU 333, 'Little Red Riding Hood'. A number of variants of ATU 333 have been recorded in European oral traditions, and it has been suggested that the group may include tales from other regions, including Africa and East Asia. However, in many of these cases, it is difficult to differentiate ATU 333 from another widespread international folktale, ATU 123, 'The Wolf and the Kids'. To shed more light on these relationships, data on 58 folktales were analysed using cladistic, Bayesian and phylogenetic network-based methods. The results demonstrate that, contrary to the claims made by critics of the historic-geographic approach, it is possible to identify ATU 333 and ATU 123 as distinct international types. They further suggest that most of the African tales can be classified as variants of ATU 123, while the East Asian tales probably evolved by blending together elements of both ATU 333 and ATU 123. These findings demonstrate that phylogenetic methods provide a powerful set of tools for testing hypotheses about cross-cultural relationships among folktales, and point towards exciting new directions for research into the transmission and evolution of oral narratives. PMID- 24236062 TI - Reproductive strategies of Aedes albopictus (Diptera: Culicidae) and implications for the sterile insect technique. AB - Male insects are expected to optimize their reproductive strategy according to the availability of sperm or other ejaculatory materials, and to the availability and reproductive status of females. Here, we investigated the reproductive strategy and sperm management of male and virgin female Aedes albopictus, a mosquito vector of chikungunya and dengue viruses. The dynamics of semen transfer to the female bursa inseminalis and spermathecae were observed. Double-mating experiments were conducted to study the effect of time lapsed or an oviposition event between two copulations on the likelihood of a female double-insemination and the use of sperm for egg fertilization; untreated fertile males and radio sterilised males were used for this purpose. Multiple inseminations and therefore the possibility of sperm competition were limited to matings closely spaced in time. When two males consecutively mated the same female within a 40 min interval, in ca. 15% of the cases did both males sire progeny. When the intervals between the copulations were longer, all progeny over several gonotrophic cycles were offspring of the first male. The mating behavior of males was examined during a rapid sequence of copulations. Male Ae. albopictus were parceling sperm allocation over several matings; however they would also attempt to copulate with females irrespective of the available sperm supply or accessory gland secretion material. During each mating, they transferred large quantities of sperm that was not stored for egg fertilization, and they attempted to copulate with mated females with a low probability of transferring their genes to the next generation. The outcomes of this study provided in addition some essential insights with respect to the sterile insect technique (SIT) as a vector control method. PMID- 24236064 TI - Cranial Endocast of the lambeosaurine hadrosaurid Amurosaurus riabinini from the Amur region, Russia. AB - Information on the structure of the brain of the lambeosaurine hadrosaurid dinosaur Amurosaurus riabinini, from the Late Maastrichtian of Blagoveschensk, Far Eastern Russia, is presented based on endocranial casts. The endocasts are compared with physical and digital endocasts of other dinosaurs. The olfactory tract was large. The cerebral hemispheres are enlarged and round, illustrating the important development of this part of the brain in hadrosaurids. The pituitary body is enlarged as well, perhaps prefiguring the large size attained by hadrosaurids. The EQ of Amurosaurus was similar to that of the lambeosaurine dinosaur Hypacrosaurus altispinus and was relatively larger than in most extant non-avian reptiles, including sauropod and ceratopsian dinosaurs. However, it was apparently relatively smaller than those of most theropod dinosaurs. The relatively large size of the cerebrum is consistent with the range and complexity of social behaviors inferred for lambeosaurine dinosaurs. PMID- 24236063 TI - Identification and characterization of angiogenesis targets through proteomic profiling of endothelial cells in human cancer tissues. AB - Genomic and proteomic analysis of normal and cancer tissues has yielded abundant molecular information for potential biomarker and therapeutic targets. Considering potential advantages in accessibility to pharmacological intervention, identification of targets resident on the vascular endothelium within tumors is particularly attractive. By employing mass spectrometry (MS) as a tool to identify proteins that are over-expressed in tumor-associated endothelium relative to normal cells, we aimed to discover targets that could be utilized in tumor angiogenesis cancer therapy. We developed proteomic methods that allowed us to focus our studies on the discovery of cell surface/secreted proteins, as they represent key antibody therapeutic and biomarker opportunities. First, we isolated endothelial cells (ECs) from human normal and kidney cancer tissues by FACS using CD146 as a marker. Additionally, dispersed human colon and lung cancer tissues and their corresponding normal tissues were cultured ex-vivo and their endothelial content were preferentially expanded, isolated and passaged. Cell surface proteins were then preferentially captured, digested with trypsin and subjected to MS-based proteomic analysis. Peptides were first quantified, and then the sequences of differentially expressed peptides were resolved by MS analysis. A total of 127 unique non-overlapped (157 total) tumor endothelial cell over-expressed proteins identified from directly isolated kidney associated ECs and those identified from ex-vivo cultured lung and colon tissues including known EC markers such as CD146, CD31, and VWF. The expression analyses of a panel of the identified targets were confirmed by immunohistochemistry (IHC) including CD146, B7H3, Thy-1 and ATP1B3. To determine if the proteins identified mediate any functional role, we performed siRNA studies which led to previously unidentified functional dependency for B7H3 and ATP1B3. PMID- 24236065 TI - An effective solution to discover synergistic drugs for anti-cerebral ischemia from traditional Chinese medicinal formulae. AB - Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM). Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ), which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G), berberine (B) and jasminoidin (J) was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G): 2(B): 0.5(J), and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could greatly improve the efficiency in finding new combination drug from TCM. PMID- 24236066 TI - Overexpressing STAMP2 improves insulin resistance in diabetic ApoE-/-/LDLR-/- mice via macrophage polarization shift in adipose tissues. AB - STAMP2 is a counterregulator of inflammation and insulin resistance. The aim of this study is to investigate whether activation of STAMP2 improves insulin resistance by regulating macrophage polarization in adipose tissues. The diabetic ApoE-/-/LDLR-/- mouse model was induced by high-fat diet and low-dose streptozotocin. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Infiltration of M1/M2 macrophages and inflammatory cytokines were investigated by immunohistochemistry. We then used gene overexpression to investigate the effect of STAMP2 on macrophages infiltration and polarization and inflammatory cytokines expression. Our results showed that infiltration of macrophages, the ratio of M1/M2 macrophages and the expression of pro inflammatory cytokines were enhanced and STAMP2 was downregulated in adipose tissues of diabetic ApoE-/-/LDLR-/- mice compared with control mice. STAMP2 gene overexpression could significantly reduce macrophages infiltration, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines in epididymal and brown adipose tissues, improving insulin resistance. Our results suggested that STAMP2 gene overexpression may improve insulin resistance via regulating macrophage polarization in visceral and brown adipose tissues. PMID- 24236067 TI - Macroscopic equations governing noisy spiking neuronal populations with linear synapses. AB - Deriving tractable reduced equations of biological neural networks capturing the macroscopic dynamics of sub-populations of neurons has been a longstanding problem in computational neuroscience. In this paper, we propose a reduction of large-scale multi-population stochastic networks based on the mean-field theory. We derive, for a wide class of spiking neuron models, a system of differential equations of the type of the usual Wilson-Cowan systems describing the macroscopic activity of populations, under the assumption that synaptic integration is linear with random coefficients. Our reduction involves one unknown function, the effective non-linearity of the network of populations, which can be analytically determined in simple cases, and numerically computed in general. This function depends on the underlying properties of the cells, and in particular the noise level. Appropriate parameters and functions involved in the reduction are given for different models of neurons: McKean, Fitzhugh-Nagumo and Hodgkin-Huxley models. Simulations of the reduced model show a precise agreement with the macroscopic dynamics of the networks for the first two models. PMID- 24236068 TI - Multiple MAPK cascades regulate the transcription of IME1, the master transcriptional activator of meiosis in Saccharomyces cerevisiae. AB - The choice between alternative developmental pathways is primarily controlled at the level of transcription. Induction of meiosis in budding yeasts in response to nutrient levels provides a system to investigate the molecular basis of cellular decision-making. In Saccharomyces cerevisiae, entry into meiosis depends on multiple signals converging upon IME1, the master transcriptional activator of meiosis. Here we studied the regulation of the cis-acting regulatory element Upstream Activation Signal (UAS)ru, which resides within the IME1 promoter. Guided by our previous data acquired using a powerful high-throughput screening system, here we provide evidence that UASru is regulated by multiple stimuli that trigger distinct signal transduction pathways as follows: (i) The glucose signal inhibited UASru activity through the cyclic AMP (cAMP/protein kinase A (PKA) pathway, targeting the transcription factors (TFs), Com2 and Sko1; (ii) high osmolarity activated UASru through the Hog1/mitogen-activated protein kinase (MAPK) pathway and its corresponding TF Sko1; (iii) elevated temperature increased the activity of UASru through the cell wall integrity pathway and the TFs Swi4/Mpk1 and Swi4/Mlp1; (iv) the nitrogen source repressed UASru activity through Sum1; and (v) the absence of a nitrogen source was detected and transmitted to UASru by the Kss1 and Fus3 MAPK pathways through their respective downstream TFs, Ste12/Tec1 and Ste12/Ste12 as well as by their regulators Dig1/2. These signaling events were specific to UASru; they did not affect the mating and filamentation response elements that are regulated by MAPK pathways. The complex regulation of UASru through all the known vegetative MAPK pathways is unique to S. cerevisiae and is specific for IME1, likely because it is the master regulator of gametogenesis. PMID- 24236069 TI - Type 2 diabetes: an independent risk factor for tuberculosis: a nationwide population-based study. AB - OBJECTIVE: Tuberculosis continues to be a major global health problem. We wanted to investigate whether Type 2 diabetes was a risk factor for tuberculosis in an Asian population. METHODS: From Taiwan's National Health Insurance Research Database, we collected data from 31,237 female patients with type 2 diabetes and 92,642 female controls and 32,493 male patients with type 2 diabetes and 96,977 male controls. Cox proportional hazard regression was performed to evaluate independent risk factors for tuberculosis in all patients and to identify risk factors in patients with type 2 diabetes. RESULTS: During the study period, both female (standardized incidence ratio (SIR): 1.40, p<0.01) and male (SIR: 1.48, p<0.01) patients with type 2 diabetes were found to have a significantly higher rate of incident tuberculosis than the control group. Type 2 diabetes (HR:1.31, 1.23-1.39, p<0.001) was significantly associated with tuberculosis after adjusting sex, age, bronchiectasis, asthma and chronic obstructive lung disease. CONCLUSIONS: Patients with type 2 diabetes have a higher risk of tuberculosis compared to control subjects after adjusting for confounding factors. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions. Therefore, preventive measures, including addressing the possibility that type 2 diabetes increase the individual's susceptibility for incident TB, should be taken to further reduce the incidence of tuberculosis. PMID- 24236070 TI - Regulation of glucose transporter expression in human intestinal Caco-2 cells following exposure to an anthocyanin-rich berry extract. AB - Polyphenols contained within plant tissues are consumed in significant amounts in the human diet and are known to influence a number of biological processes. This study investigated the effects of an anthocyanin-rich berry-extract on glucose uptake by human intestinal Caco-2 cells. Acute exposure (15 min) to berry extract (0.125%, w/v) significantly decreased both sodium-dependent (Total uptake) and sodium-independent (facilitated uptake) 3H-D-glucose uptake. In longer-term studies, SGLT1 mRNA and GLUT2 mRNA expression were reduced significantly. Polyphenols are known to interact directly with glucose transporters to regulate the rate of glucose absorption. Our in vitro data support this mechanism and also suggest that berry flavonoids may modulate post-prandial glycaemia by decreasing glucose transporter expression. Further studies are warranted to investigate the longer term effects of berry flavonoids on the management of glycaemia in human volunteers. PMID- 24236071 TI - Development and validation of the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) for primary care patients with type 2 diabetes. AB - OBJECTIVES: To develop and evaluate the psychometric properties of a Chinese questionnaire which assesses the barriers and enablers to commencing insulin in primary care patients with poorly controlled Type 2 diabetes. RESEARCH DESIGN AND METHOD: Questionnaire items were identified using literature review. Content validation was performed and items were further refined using an expert panel. Following translation, back translation and cognitive debriefing, the translated Chinese questionnaire was piloted on target patients. Exploratory factor analysis and item-scale correlations were performed to test the construct validity of the subscales and items. Internal reliability was tested by Cronbach's alpha. RESULTS: Twenty-seven identified items underwent content validation, translation and cognitive debriefing. The translated questionnaire was piloted on 303 insulin naive (never taken insulin) Type 2 diabetes patients recruited from 10 government funded primary care clinics across Hong Kong. Sufficient variability in the dataset for factor analysis was confirmed by Bartlett's Test of Sphericity (P<0.001). Using exploratory factor analysis with varimax rotation, 10 factors were generated onto which 26 items loaded with loading scores > 0.4 and Eigenvalues >1. Total variance for the 10 factors was 66.22%. Kaiser-Meyer-Olkin measure was 0.725. Cronbach's alpha coefficients for the first four factors were >=0.6 identifying four sub-scales to which 13 items correlated. Remaining sub scales and items with poor internal reliability were deleted. The final 13-item instrument had a four scale structure addressing: 'Self-image and stigmatization'; 'Factors promoting self-efficacy; 'Fear of pain or needles'; and 'Time and family support'. CONCLUSION: The Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) appears to be a reliable and valid measure for assessing barriers to starting insulin. This short instrument is easy to administer and may be used by healthcare providers and researchers as an assessment tool for Chinese diabetic primary care patients, including the elderly, who are unwilling to start insulin. PMID- 24236072 TI - Single, double and quadruple alanine substitutions at oligomeric interfaces identify hydrophobicity as the key determinant of human neutrophil alpha defensin HNP1 function. AB - HNP1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including Tyr16, Ile20, Leu25, and Phe28. Previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. Here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: I20A-HNP1 and L25A-HNP1, plus the double alanine mutants I20A/L25A-HNP1 and Y16A/F28A-HNP1, and the quadruple alanine mutant Y16A/I20A/L25A/F28A-HNP1. We tested binding to HIV-1 gp120 and HNP1 by surface plasmon resonance, binding to HIV-1 gp41 and HNP1 by fluorescence polarization, inhibition of anthrax lethal factor, and antibacterial activity using the virtual colony count assay. Similar to the previously described single mutant W26A-HNP1, the quadruple mutant displayed the least activity in all functional assays, followed by the double mutant Y16A/F28A-HNP1. The effects of the L25A and I20A single mutations were milder than the double mutant I20A/L25A-HNP1. Crystallographic studies confirmed the correct folding and disulfide pairing, and depicted an array of dimeric and tetrameric structures. These results indicate that side chain hydrophobicity is the critical factor that determines activity at these positions. PMID- 24236073 TI - Tissue specific localization of pectin-Ca2+ cross-linkages and pectin methyl esterification during fruit ripening in tomato (Solanum lycopersicum). AB - Fruit ripening is one of the developmental processes accompanying seed development. The tomato is a well-known model for studying fruit ripening and development, and the disassembly of primary cell walls and the middle lamella, such as through pectin de-methylesterified by pectin methylesterase (PE) and depolymerization by polygalacturonase (PG), is generally accepted to be one of the major changes that occur during ripening. Although many reports of the changes in pectin during tomato fruit ripening are focused on the relation to softening of the pericarp or the Blossom-end rot by calcium (Ca2+) deficiency disorder, the changes in pectin structure and localization in each tissues during tomato fruit ripening is not well known. In this study, to elucidate the tissue specific role of pectin during fruit development and ripening, we examined gene expression, the enzymatic activities involved in pectin synthesis and depolymerisation in fruit using biochemical and immunohistochemical analyses, and uronic acids and calcium (Ca)-bound pectin were determined by secondary ion microprobe mass spectrometry. These results show that changes in pectin properties during fruit development and ripening have tissue-specific patterns. In particular, differential control of pectin methyl-esterification occurs in each tissue. Variations in the cell walls of the pericarp are quite different from that of locular tissues. The Ca-binding pectin and hairy pectin in skin cell layers are important for intercellular and tissue-tissue adhesion. Maintenance of the globular form and softening of tomato fruit may be regulated by the arrangement of pectin structures in each tissue. PMID- 24236074 TI - Comparison of diabetes risk score estimates and cardiometabolic risk profiles in a middle-aged Irish population. AB - BACKGROUND: To compare diabetes risk assessment tools in estimating risk of developing type 2 diabetes (T2DM) and to evaluate cardiometabolic risk profiles in a middle-aged Irish population. METHODS: Future risk of developing T2DM was estimated using 7 risk scores, including clinical measures with or without anthropometric, biological and lifestyle data, in the cross-sectional Mitchelstown cohort of 2,047 middle-aged men and women. Cardiometabolic phenotypes including markers of glucose metabolism, inflammatory and lipid profiles were determined. RESULTS: Estimates of subjects at risk for developing T2DM varied considerably according to the risk assessment tool used (0.3% to 20%), with higher proportions of males at risk (0-29.2% vs. 0.1-13.4%, for men and women, respectively). Extrapolated to the Irish population of similar age, the overall number of adults at high risk of developing T2DM ranges from 3,378 to 236,632. Numbers of non-optimal metabolic features were generally greater among those at high risk of developing T2DM. However, cardiometabolic profile characterisation revealed that only those classified at high risk by the Griffin (UK Cambridge) score displayed a more pro-inflammatory, obese, hypertensive, dysglycaemic and insulin resistant metabolic phenotype. CONCLUSIONS: Most diabetes risk scores examined offer limited ability to identify subjects with metabolic abnormalities and at risk of developing T2DM. Our results highlight the need to validate diabetes risk scoring tools for each population studied and the potential for developing an Irish diabetes risk score, which may help to promote self awareness and identify high risk individuals and diabetes hot spots for targeted public health interventions. PMID- 24236075 TI - Choose your weapon: defensive behavior is associated with morphology and performance in scorpions. AB - Morphology can be adaptive through its effect on performance of an organism. The effect of performance may, however, be modulated by behavior; an organism may choose a behavioral option that does not fully utilize its maximum performance. Behavior may therefore be decoupled from morphology and performance. To gain insight into the relationships between these levels of organization, we combined morphological data on defensive structures with measures of defensive performance, and their utilization in defensive behavior. Scorpion species show significant variation in the morphology and performance of their main defensive structures; their chelae (pincers) and the metasoma ("tail") carrying the stinger. Our data show that size-corrected pinch force varies to almost two orders of magnitude among species, and is correlated with chela morphology. Chela and metasoma morphology are also correlated to the LD50 of the venom, corroborating the anecdotal rule that dangerously venomous scorpions can be recognized by their chelae and metasoma. Analyses of phylogenetic independent contrasts show that correlations between several aspects of chela and metasoma morphology, performance and behavior are present. These correlations suggest co evolution of behavior with morphology and performance. Path analysis found a performance variable (pinch force) to partially mediate the relationship between morphology (chela aspect ratio) and behavior (defensive stinger usage). We also found a correlation between two aspects of morphology: pincer finger length correlates with the relative "thickness" (aspect ratio) of the metasoma. This suggests scorpions show a trade-off between their two main weapon complexes: the metasoma carrying the stinger, and the pedipalps carrying the chelae. PMID- 24236076 TI - The prognostic value of amplitude-integrated EEG in full-term neonates with seizures. AB - Neonatal seizures pose a high risk for adverse outcome in survived infants. While the prognostic value of amplitude-integrated electroencephalogram (aEEG) is well established in neonates with encephalopathy and asphyxia, neonatal seizure studies focusing on the direct correlation between early aEEG measurement and subsequent neurologic outcome are scarce. In this study, the prognostic value of aEEG features was systematically analyzed in 143 full-term neonates to identify prognostic indicators of neurodevelopmental outcome. Neonatal aEEG features of background pattern, cyclicity, and seizure activity, as well as the etiology of neonatal seizures, were significantly associated with neurodevelopmental outcome at one year of age. aEEG background pattern was highly associated with neurologic outcomes (chi2 = 116.9), followed by aEEG cyclicity (chi2 = 87.2) and seizure etiology (chi2 = 79.3). Multiple linear regression showed that the four predictors explained 71.2% of the variation in neurological outcome, with standardized beta coefficients of 0.44, 0.24, 0.22, and 0.14 for the predictors of aEEG background pattern, cyclicity, etiology, and aEEG seizure activity, respectively. This clinically applicable scoring system based on etiology and three aEEG indices would allow pediatricians to assess the risk for neurodevelopmental impairment and facilitate an early intervention in newborns developing seizures. PMID- 24236077 TI - The tuberculosis vaccine candidate Bacillus Calmette-Guerin DeltaureC::hly coexpressing human interleukin-7 or -18 enhances antigen-specific T cell responses in mice. AB - Bacillus Calmette-Guerin (BCG), the only approved tuberculosis vaccine, provides only limited protection. Previously, we generated a recombinant derivative (BCG DeltaureC::hly), which secretes the pore-forming toxin listeriolysin O (LLO) of Listeria monocytogenes. This vaccine shows superior protection against tuberculosis in preclinical models and is safe in humans. Here we describe two new vaccine strains which express human interleukin-7 (hIL)-7 or hIL-18 in the genetic background of BCG DeltaureC::hly to modulate specific T cell immunity. Both strains exhibited an uncompromised in vitro growth pattern, while inducing a proinflammatory cytokine profile in human dendritic cells (DCs). Human DCs harbouring either strain efficiently promoted secretion of IL-2 by autologous T cells in a coculture system, suggesting superior immunogenicity. BALB/c mice vaccinated with BCG DeltaureC::hly, BCG DeltaureC::hly_hIL7 or BCG DeltaureC::hly_hIL18 developed a more robust Th1 response than after vaccination with parental BCG. Both strains provided significantly better protection than BCG in a murine Mycobacterium tuberculosis challenge model but efficacy remained comparable to that afforded by BCG DeltaureC::hly. We conclude that expression of hIL-7 or hIL-18 enhanced specific T cell responses but failed to improve protection over BCG DeltaureC::hly in mice. PMID- 24236078 TI - On the evolution of handedness: evidence for feeding biases. AB - Many theories have been put forward to explain the origins of right-handedness in humans. Here we present evidence that this preference may stem in part from a right hand advantage in grasping for feeding. Thirteen participants were asked to reach-to-grasp food items of 3 different sizes: SMALL (Cheerios(r)), MEDIUM (Froot Loops(r)), and LARGE (Oatmeal Squares(r)). Participants used both their right- and left-hands in separate blocks (50 trials each, starting order counterbalanced) to grasp the items. After each grasp, participants either a) ate the food item, or b) placed it inside a bib worn beneath his/her chin (25 trials each, blocked design, counterbalanced). The conditions were designed such that the outward and inward movement trajectories were similar, differing only in the final step of placing it in the mouth or bib. Participants wore Plato liquid crystal goggles that blocked vision between trials. All trials were conducted in closed-loop with 5000 ms of vision. Hand kinematics were recorded by an Optotrak Certus, which tracked the position of three infrared diodes attached separately to the index finger, thumb, and wrist. We found a task (EAT/PLACE) by hand (LEFT/RIGHT) interaction on maximum grip aperture (MGA; the maximum distance between the index finger and thumb achieved during grasp pre-shaping). MGAs were smaller during right-handed movements, but only when grasping with intent to eat. Follow-up tests show that the RIGHT-HAND/EAT MGA was significantly smaller than all other hand/task conditions. Because smaller grip apertures are typically associated with greater precision, our results demonstrate a right-hand advantage for the grasp-to-eat movement. From an evolutionary perspective, early humans may have preferred the hand that could grasp food with more precision, thereby maximizing the likelihood of retrieval, consumption, and consequently, survival. PMID- 24236079 TI - Crowdedness mediates the effect of social identification on positive emotion in a crowd: a survey of two crowd events. AB - Exposure to crowding is said to be aversive, yet people also seek out and enjoy crowded situations. We surveyed participants at two crowd events to test the prediction of self-categorization theory that variable emotional responses to crowding are a function of social identification with the crowd. In data collected from participants who attended a crowded outdoor music event (n = 48), identification with the crowd predicted feeling less crowded; and there was an indirect effect of identification with the crowd on positive emotion through feeling less crowded. Identification with the crowd also moderated the relation between feeling less crowded and positive emotion. In data collected at a demonstration march (n = 112), identification with the crowd predicted central (most dense) location in the crowd; and there was an indirect effect of identification with the crowd on positive emotion through central location in the crowd. Positive emotion in the crowd also increased over the duration of the crowd event. These findings are in line with the predictions of self categorization theory. They are inconsistent with approaches that suggest that crowding is inherently aversive; and they cannot easily be explained through the concept of 'personal space'. PMID- 24236080 TI - Diabetes: a risk factor for poor functional outcome after total knee arthroplasty. AB - BACKGROUND: To assess the association of diabetes with postoperative limitation of activities of daily living (ADLs) after primary total knee arthroplasty (TKA). METHODOLOGY/PRINCIPAL FINDINGS: We used the prospectively collected data from the Mayo Clinic Total Joint Registry to assess the association of diabetes and diabetes with complications with moderate-severe ADL limitation 2- and 5-years after primary TKA. Multivariable logistic regression with general estimating equations adjusted for preoperative ADL limitation, comorbidity and demographic and clinical covariates. Odds ratio (OR) and 95% confidence interval (CI) are presented. 7,139 primary TKAs at 2-years and 4,234 at 5-years constituted the cohorts. In multivariable-adjusted analyses, diabetes was associated with higher odds of moderate-severe limitation at 2- and 5-years, 1.71 (95% CI: 1.26, 2.32; P = 0.001) and 1.66 (95% CI: 1.13, 2.46; P = 0.01). Respective ORs for patients with diabetes with complications were 2.73 (95% CI: 1.47, 5.07; P = 0.001) and 2.73 (95% CI: 1.21, 6.15; P = 0.016). Sensitivity analyses that adjusted for anxiety and depression or anxiety, depression and ipsilateral hip involvement showed minimal attenuation of magnitude of the association. CONCLUSIONS/SIGNIFICANCE: In this large study of patients who underwent primary TKA, diabetes as well as its severity were independently associated with poorer functional outcome. Given the increasing rates of both diabetes as well as arthroplasty, more insight is needed into disease-related and treatment-related factors that underlie this higher risk of ADL limitation in patients with diabetes. Poor functional outcomes may be preventable by modifying the control of diabetes and associated comorbidity in pre- and post-arthroplasty periods. PMID- 24236081 TI - Antimicrobial activity of heterotrophic bacterial communities from the marine sponge Erylus discophorus (Astrophorida, Geodiidae). AB - Heterotrophic bacteria associated with two specimens of the marine sponge Erylus discophorus were screened for their capacity to produce bioactive compounds against a panel of human pathogens (Staphylococcus aureus wild type and methicillin-resistant S. aureus (MRSA), Bacillus subtilis, Pseudomonas aeruginosa, Acinetobacter baumanii, Candida albicans and Aspergillus fumigatus), fish pathogen (Aliivibrio fischeri) and environmentally relevant bacteria (Vibrio harveyi). The sponges were collected in Berlengas Islands, Portugal. Of the 212 isolated heterotrophic bacteria belonging to Alpha- and Gammaproteobacteria, Actinobacteria and Firmicutes, 31% produced antimicrobial metabolites. Bioactivity was found against both Gram positive and Gram negative and clinically and environmentally relevant target microorganisms. Bioactivity was found mainly against B. subtilis and some bioactivity against S. aureus MRSA, V. harveyi and A. fisheri. No antifungal activity was detected. The three most bioactive genera were Pseudovibrio (47.0%), Vibrio (22.7%) and Bacillus (7.6%). Other less bioactive genera were Labrenzia, Acinetobacter, Microbulbifer, Pseudomonas, Gordonia, Microbacterium, Micrococcus and Mycobacterium, Paenibacillus and Staphylococcus. The search of polyketide I synthases (PKS-I) and nonribosomal peptide synthetases (NRPSs) genes in 59 of the bioactive bacteria suggested the presence of PKS-I in 12 strains, NRPS in 3 strains and both genes in 3 strains. Our results show the potential of the bacterial community associated with Erylus discophorus sponges as producers of bioactive compounds. PMID- 24236082 TI - Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. AB - The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment. PMID- 24236083 TI - Prehispanic use of chili peppers in Chiapas, Mexico. AB - The genus Capsicum is New World in origin and represents a complex of a wide variety of both wild and domesticated taxa. Peppers or fruits of Capsicum species rarely have been identified in the paleoethnobotanical record in either Meso- or South America. We report here confirmation of Capsicum sp. residues from pottery samples excavated at Chiapa de Corzo in southern Mexico dated from Middle to Late Preclassic periods (400 BCE to 300 CE). Residues from 13 different pottery types were collected and extracted using standard techniques. Presence of Capsicum was confirmed by ultra-performance liquid chromatography (UPLC)/MS-MS Analysis. Five pottery types exhibited chemical peaks for Capsicum when compared to the standard (dihydrocapsaicin). No peaks were observed in the remaining eight samples. Results of the chemical extractions provide conclusive evidence for Capsicum use at Chiapas de Corzo during a 700 year period (400 BCE-300 CE). Presence of Capsicum in different types of culinary-associated pottery raises questions how chili pepper could have been used during this early time period. As Pre-Columbian cacao products sometimes were flavored using Capsicum, the same pottery sample set was tested for evidence of cacao using a theobromine marker: these results were negative. As each vessel that tested positive for Capsicum had a culinary use we suggest here the possibility that chili residues from the Chiapas de Corzo pottery samples reflect either paste or beverage preparations for religious, festival, or every day culinary use. Alternatively, some vessels that tested positive merely could have been used to store peppers. Most interesting from an archaeological context was the presence of Capsicum residue obtained from a spouted jar, a pottery type previously thought only to be used for pouring liquids. PMID- 24236084 TI - Demographics of the European apicultural industry. AB - Over the last few years, many European and North American countries have reported a high rate of disorders (mortality, dwindling and disappearance) affecting honeybee colonies (Apis mellifera). Although beekeeping has become an increasingly professional activity in recent years, the beekeeping industry remains poorly documented in Europe. The European Union Reference Laboratory for Honeybee Health sent a detailed questionnaire to each Member State, in addition to Kosovo and Norway, to determine the demographics and state of their beekeeping industries. Based on data supplied by the National Reference Laboratory for honeybee diseases in each European country, a European database was created to describe the beekeeping industry including the number and types of beekeepers, operation size, industry production, and health (notifiable diseases, mortalities). The total number of beekeepers in Europe was estimated at 620,000. European honey production was evaluated at around 220,000 tons in 2010. The price of honey varied from 1.5 to 40 ?/kg depending on the country and on the distribution network. The estimated colony winter mortality varied from 7 to 28% depending on the country and the origin of the data (institutional survey or beekeeping associations). This survey documents the high heterogeneity of the apicultural industry within the European Union. The high proportion of non professional beekeepers and the small mean number of colonies per beekeeper were the only common characteristics at European level. The tremendous variation in European apicultural industries has implication for any comprehensive epidemiological or economic analysis of the industry. This variability needs to be taken into account for such analysis as well as for future policy development. The industry would be served if beekeeping registration was uniformly implemented across member states. Better information on the package bee and queen production would help in understanding the ability of the industry to replace lost honey bee stocks. PMID- 24236085 TI - Characterization of hydrophobic peptides in the presence of detergent by photoionization mass spectrometry. AB - The characterization of membrane proteins is still challenging. The major issue is the high hydrophobicity of membrane proteins that necessitates the use of detergents for their extraction and solubilization. The very poor compatibility of mass spectrometry with detergents remains a tremendous obstacle in studies of membrane proteins. Here, we investigated the potential of atmospheric pressure photoionization (APPI) for mass spectrometry study of membrane proteins. This work was focused on the tetraspanin CD9 and the multidrug transporter BmrA. A set of peptides from CD9, exhibiting a broad range of hydropathicity, was investigated using APPI as compared to electrospray ionization (ESI). Mass spectrometry experiments revealed that the most hydrophobic peptides were hardly ionized by ESI whereas all peptides, including the highly hydrophobic one that corresponds to the full sequence of the first transmembrane domain of CD9, were easily ionized by APPI. The native protein BmrA purified in the presence of the non-ionic detergent beta-D-dodecyl maltoside (DDM) was digested in-solution using trypsin. The resulting peptides were investigated by flow injection analysis of the mixture followed by mass spectrometry. Upon ESI, only detergent ions were detected and the ionic signals from the peptides were totally suppressed. In contrast, APPI allowed many peptides distributed along the sequence of the protein to be detected. Furthermore, the parent ion corresponding to the first transmembrane domain of the protein BmrA was detected under APPI conditions. Careful examination of the APPI mass spectrum revealed a-, b-, c- and y- fragment ions generated by in-source fragmentation. Those fragment ions allowed unambiguous structural characterization of the transmembrane domain. In conclusion, APPI-MS appears as a versatile method allowing the ionization and fragmentation of hydrophobic peptides in the presence of detergent. PMID- 24236087 TI - The name-letter-effect in groups: sharing initials with group members increases the quality of group work. AB - Although the name-letter-effect has been demonstrated reliably in choice contexts, recent research has called into question the existence of the name letter-effect-the tendency among people to make choices that bear remarkable similarity with the letters in their own name. In this paper, we propose a connection between the name-letter-effect and interpersonal, group-level behavior that has not been previously captured in the literature. Specifically, we suggest that sharing initials with other group members promotes positive feelings toward those group members that in turn affect group outcomes. Using both field and laboratory studies, we found that sharing initials with group members cause groups to perform better by demonstrating greater performance, collective efficacy, adaptive conflict, and accuracy (on a hidden-profile task). Although many studies have investigated the effects of member similarity on various outcomes, our research demonstrates how minimal a degree of similarity among members is sufficient to influence quality of group outcomes. PMID- 24236086 TI - Identification and molecular characterization of FKF1 and GI homologous genes in soybean. AB - In Arabidopsis, FKF1 (FLAVIN BINDING, KELCH REPEAT, F-BOX1) and GI (GIGANTEA) play important roles in flowering pathway through regulating daytime CO (CONSTANS) expression, and such a function is conserved across plants studied. But related reports are limited for soybean. In this study, we cloned FKF1 and GI homologs in soybean, and named as GmFKF1, GmFKF2, GmGI1, GmGI2, and GmGI3, respectively. GmGI1 had two alternative splicing forms, GmGI1alpha and GmGI1beta. GmFKF1/2 transcripts were diurnally regulated, with a peak at zeitgeber time 12 (ZT12) in long days and at ZT10 in short days. The diurnal phases between GmGIs transcript levels greatly differed. GmGI2 expression was regulated by both the circadian clock and photoperiod. But the rhythmic phases of GmGI1 and GmGI3 expression levels were mainly conferred by long days. GmFKFs shared similar spatio-temporal expression profiles with GmGIs in all of the tissue/organs in different developmental stages in both LD and SD. Both GmFKF and GmGI proteins were targeted to the nucleus. Yeast two hybrid assays showed GmFKF1/GmFKF2 interacted with GmGI1/GmGI2/GmCDF1 (CYCLING DOF FACTOR CDF1 homolog in soybean); and the LOV (Light, Oxygen, or Voltage) domain in GmFKF1/GmFKF2 played an important role in these interactions. N-terminus of GmGI2 was sufficient to mediate its interaction with GmCDF1. Interestingly, N-terminus not full of GmGI3 interacted with GmFKF1/GmFKF2/GmCDF1. Ectopic over-expression of the GmFKF1 or GmFKF2 in Arabidopsis enhanced flowering in SD. Collectively, GmFKF and GmGI in soybean had conserved functional domains at DNA sequence level, but specific characters at function level with their homologs in other plants. PMID- 24236088 TI - Role of tumor necrosis factor-alpha in the human systemic endotoxin-induced transcriptome. AB - TNFalpha has been implicated in the pathogenesis of various inflammatory diseases. Different strategies to inhibit TNFalpha in patients with sepsis and chronic inflammatory conditions have shown contrasting outcomes. Although TNFalpha inhibitors are widely used in clinical practice, the impact of TNFalpha antagonism on white blood cell gene expression profiles during acute inflammation in humans in vivo has not been assessed. We here leveraged the established model of human endotoxemia to examine the effect of the TNFalpha antagonist, etanercept, on the genome-wide transcriptional responses in circulating leukocytes induced by intravenous LPS administration in male subjects. Etanercept pre-treatment resulted in a markedly dampened transcriptional response to LPS. Gene co-expression network analysis revealed this LPS-induced transcriptome can be categorized as TNFalpha responsive and non-responsive modules. Highly significant TNFalpha responsive modules include NF-kB signaling, antiviral responses and T-cell mediated responses. Within these TNFalpha responsive modules we delineate fundamental genes involved in epigenetic modifications, transcriptional initiation and elongation. Thus, we provide comprehensive information about molecular pathways that might be targeted by therapeutic interventions that seek to inhibit TNFalpha activity during human inflammatory diseases. PMID- 24236089 TI - Functional and muscular adaptations in an experimental model for isometric strength training in mice. AB - Exercise training induces muscular adaptations that are highly specific to the type of exercise. For a systematic study of the differentiated exercise adaptations on a molecular level mouse models have been used successfully. The aim of the current study was to develop a suitable mouse model of isometric strength exercise training characterized by specific adaptations known from strength training. C57BL/6 mice performed an isometric strength training (ST) for 10 weeks 5 days/week. Additionally, either a sedentary control group (CT) or a regular endurance training group (ET) groups were used as controls. Performance capacity was determined by maximum holding time (MHT) and treadmill spirometry, respectively. Furthermore, muscle fiber types and diameter, muscular concentration of phosphofructokinase 1 (PFK), succinate dehydrogenase (SDHa), and glucose transporter type 4 (GLUT4) were determined. In a further approach, the effect of ST on glucose intolerance was tested in diabetic mice. In mice of the ST group we observed an increase of MHT in isometric strength tests, a type II fiber hypertrophy, and an increased GLUT4 protein content in the membrane fraction. In contrast, in mice of the ET group an increase of VO(2max), a shift to oxidative muscle fiber type and an increase of oxidative enzyme content was measured. Furthermore strength training was effective in reducing glucose intolerance in mice fed a high fat diet. An effective murine strength training model was developed and evaluated, which revealed marked differences in adaptations known from endurance training. This approach seems also suitable to test for therapeutical effects of strength training. PMID- 24236090 TI - Dietary ecology of Murinae (Muridae, Rodentia): a geometric morphometric approach. AB - Murine rodents represent a highly diverse group, which displays great ecological versatility. In the present paper we analyse the relationship between dental morphology, on one hand, using geometric morphometrics based upon the outline of first upper molar and the dietary preference of extant murine genera, on the other. This ecomorphological study of extant murine rodents demonstrates that dietary groups can be distinguished with the use of a quantitative geometric morphometric approach based on first upper molar outline. A discriminant analysis of the geometric morphometric variables of the first upper molars enables us to infer the dietary preferences of extinct murine genera from the Iberian Peninsula. Most of the extinct genera were omnivore; only Stephanomys showed a pattern of dental morphology alike that of the herbivore genera. PMID- 24236091 TI - A community-based, case-control study evaluating mortality reduction from gastric cancer by endoscopic screening in Japan. AB - AIMS: Although the incidence of gastric cancer has decreased in the last 3 decades, it remains the second leading cause of cancer death worldwide. In Asian countries, the burden of gastric cancer has remained, and cancer screening is normally expected to reduce gastric cancer death. We conducted a community-based, case-control study to evaluate the reduction of mortality from gastric cancer by endoscopic screening. METHODS: Case subjects were defined as individuals who had died of gastric cancer between 2003 and 2006 in 4 cities in Tottori Prefecture, and between 2006 and 2010 in Niigata City, Japan. Up to 6 control subjects were matched by sex, birth year (+/-3 years), and the residence of each corresponding case subject from the population lists in the study areas. Control subjects were required to be disease-free at the time when the corresponding case subjects were diagnosed as having gastric cancer. The odds ratios (ORs) were calculated for those who had participated in endoscopic or radiographic screening before the reference date when the case subjects were diagnosed as having gastric cancer, compared with subjects who had never participated in any screening. Conditional logistic-regression models for matched sets were used to estimate the ORs and 95% confidence intervals (CIs). RESULTS: The case subjects consisted of 288 men and 122 women for case subjects, with 2,292 matched control subjects. Compared with those who had never been screened before the date of diagnosis of gastric cancer in the case subjects, the ORs within 36 months from the date of diagnosis were 0.695 (95% CI: 0.489-0.986) for endoscopic screening and 0.865 (95% CI : 0.631 1.185) for radiographic screening. CONCLUSIONS: The results suggest a 30% reduction in gastric cancer mortality by endoscopic screening compared with no screening within 36 months before the date of diagnosis of gastric cancer. PMID- 24236092 TI - Identification of miRNAs and their target genes in peach (Prunus persica L.) using high-throughput sequencing and degradome analysis. AB - MicroRNAs play critical roles in various biological and metabolic processes. The function of miRNAs has been widely studied in model plants such as Arabidopsis and rice. However, the number of identified miRNAs and related miRNA targets in peach (Prunus persica) is limited. To understand further the relationship between miRNAs and their target genes during tissue development in peach, a small RNA library and three degradome libraries were constructed from three tissues for deep sequencing. We identified 117 conserved miRNAs and 186 novel miRNA candidates in peach by deep sequencing and 19 conserved miRNAs and 13 novel miRNAs were further evaluated for their expression by RT-qPCR. The number of gene targets that were identified for 26 conserved miRNA families and 38 novel miRNA candidates, were 172 and 87, respectively. Some of the identified miRNA targets were abundantly represented as conserved miRNA targets in plant. However, some of them were first identified and showed important roles in peach development. Our study provides information concerning the regulatory network of miRNAs in peach and advances our understanding of miRNA functions during tissue development. PMID- 24236093 TI - The role of forgetting in undermining good intentions. AB - Evaluating others is a fundamental feature of human social interaction--we like those who help more than those who hinder. In the present research, we examined social evaluation of those who not only intentionally performed good and bad actions but also those to whom good things have happened (the lucky) and those to whom bad things have happened (the unlucky). In Experiment 1a, subjects demonstrated a sympathetic preference for the unlucky. However, under cognitive load (Experiment 1b), no such preference was expressed. Further, in Experiments 2a and 2b, when a time delay between impression formation (learning) and evaluation (memory test) was introduced, results showed that younger (Experiment 2a) and older adults (Experiment 2b) showed a significant preference for the lucky. Together these experiments show that a consciously motivated sympathetic preference for those who are unlucky dissolves when memory is disrupted. The observed dissociation provides evidence for the presence of conscious good intentions (favoring the unlucky) and the cognitive compromising of such intentions when memory fails. PMID- 24236094 TI - Depletion of spleen macrophages delays AA amyloid development: a study performed in the rapid mouse model of AA amyloidosis. AB - AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM), marginal zone macrophages (MZM), metallophilic marginal zone macrophages (MMZM). MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation. PMID- 24236095 TI - Targeted RNA-sequencing with competitive multiplex-PCR amplicon libraries. AB - Whole transcriptome RNA-sequencing is a powerful tool, but is costly and yields complex data sets that limit its utility in molecular diagnostic testing. A targeted quantitative RNA-sequencing method that is reproducible and reduces the number of sequencing reads required to measure transcripts over the full range of expression would be better suited to diagnostic testing. Toward this goal, we developed a competitive multiplex PCR-based amplicon sequencing library preparation method that a) targets only the sequences of interest and b) controls for inter-target variation in PCR amplification during library preparation by measuring each transcript native template relative to a known number of synthetic competitive template internal standard copies. To determine the utility of this method, we intentionally selected PCR conditions that would cause transcript amplification products (amplicons) to converge toward equimolar concentrations (normalization) during library preparation. We then tested whether this approach would enable accurate and reproducible quantification of each transcript across multiple library preparations, and at the same time reduce (through normalization) total sequencing reads required for quantification of transcript targets across a large range of expression. We demonstrate excellent reproducibility (R2 = 0.997) with 97% accuracy to detect 2-fold change using External RNA Controls Consortium (ERCC) reference materials; high inter-day, inter-site and inter-library concordance (R2 = 0.97-0.99) using FDA Sequencing Quality Control (SEQC) reference materials; and cross-platform concordance with both TaqMan qPCR (R2 = 0.96) and whole transcriptome RNA-sequencing following "traditional" library preparation using Illumina NGS kits (R2 = 0.94). Using this method, sequencing reads required to accurately quantify more than 100 targeted transcripts expressed over a 107-fold range was reduced more than 10,000-fold, from 2.3*109 to 1.4*105 sequencing reads. These studies demonstrate that the competitive multiplex-PCR amplicon library preparation method presented here provides the quality control, reproducibility, and reduced sequencing reads necessary for development and implementation of targeted quantitative RNA sequencing biomarkers in molecular diagnostic testing. PMID- 24236096 TI - Molecular cloning and characterization of porcine Na+/K+-ATPase isoforms alpha1, alpha2, alpha3 and the ATP1A3 promoter. AB - Na+/K+-ATPase maintains electrochemical gradients of Na+ and K+ essential for a variety of cellular functions including neuronal activity. The alpha-subunit of the Na+/K+-ATPase exists in four different isoforms (alpha1-alpha4) encoded by different genes. With a view to future use of pig as an animal model in studies of human diseases caused by Na+/K+-ATPase mutations, we have determined the porcine coding sequences of the alpha1-alpha3 genes, ATP1A1, ATP1A2, and ATP1A3, their chromosomal localization, and expression patterns. Our ATP1A1 sequence accords with the sequences from several species at five positions where the amino acid residue of the previously published porcine ATP1A1 sequence differs. These corrections include replacement of glutamine 841 with arginine. Analysis of the functional consequences of substitution of the arginine revealed its importance for Na+ binding, which can be explained by interaction of the arginine with the C terminus, stabilizing one of the Na+ sites. Quantitative real-time PCR expression analyses of porcine ATP1A1, ATP1A2, and ATP1A3 mRNA showed that all three transcripts are expressed in the embryonic brain as early as 60 days of gestation. Expression of alpha3 is confined to neuronal tissue. Generally, the expression patterns of ATP1A1, ATP1A2, and ATP1A3 transcripts were found similar to their human counterparts, except for lack of alpha3 expression in porcine heart. These expression patterns were confirmed at the protein level. We also report the sequence of the porcine ATP1A3 promoter, which was found to be closely homologous to its human counterpart. The function and specificity of the porcine ATP1A3 promoter was analyzed in transgenic zebrafish, demonstrating that it is active and drives expression in embryonic brain and spinal cord. The results of the present study provide a sound basis for employing the ATP1A3 promoter in attempts to generate transgenic porcine models of neurological diseases caused by ATP1A3 mutations. PMID- 24236098 TI - alpha/beta-hydrolase domain containing protein 15 (ABHD15)--an adipogenic protein protecting from apoptosis. AB - Our knowledge about adipocyte metabolism and development is steadily growing, yet many players are still undefined. Here, we show that alpha/beta-hydrolase domain containing protein 15 (Abhd15) is a direct and functional target gene of peroxisome proliferator-activated receptor gamma (PPARgamma), the master regulator of adipogenesis. In line, Abhd15 is mainly expressed in brown and white adipose tissue and strongly upregulated during adipogenesis in various murine and human cell lines. Stable knockdown of Abhd15 in 3T3-L1 cells evokes a striking differentiation defect, as evidenced by low lipid accumulation and decreased expression of adipocyte marker genes. In preconfluent cells, knockdown of Abhd15 leads to impaired proliferation, which is caused by apoptosis, as we see an increased SubG1 peak, caspase 3/7 activity, and BAX protein expression as well as a reduction in anti-apoptotic BCL-2 protein. Furthermore, apoptosis-inducing amounts of palmitic acid evoke a massive increase of Abhd15 expression, proposing an apoptosis-protecting role for ABHD15. On the other hand, in mature adipocytes physiological (i.e. non-apoptotic) concentrations of palmitic acid down-regulate Abhd15 expression. Accordingly, we found that the expression of Abhd15 in adipose tissue is reduced in physiological situations with high free fatty acid levels, like high-fat diet, fasting, and aging as well as in genetically obese mice. Collectively, our results position ABHD15 as an essential component in the development of adipocytes as well as in apoptosis, thereby connecting two substantial factors in the regulation of adipocyte number and size. Together with its intricate regulation by free fatty acids, ABHD15 might be an intriguing new target in obesity and diabetes research. PMID- 24236099 TI - On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks. AB - A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2) synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT). Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1) in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2) whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities. PMID- 24236097 TI - MicroRNA-20a constrains p300-driven myocardial angiogenic transcription by direct targeting of p300. AB - OBJECTIVE: To characterize downstream effectors of p300 acetyltransferase in the myocardium. BACKGROUND: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known. METHODS AND RESULTS: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17~92 cluster in vivo. Confirming this finding, both miR-17 3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17~92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3'UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts. CONCLUSION: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a. PMID- 24236100 TI - Reduced nasal nitric oxide production in cystic fibrosis patients with elevated systemic inflammation markers. AB - BACKGROUND: Nitric oxide (NO) is produced within the respiratory tract and can be detected in exhaled bronchial and nasal air. The concentration varies in specific diseases, being elevated in patients with asthma and bronchiectasis, but decreased in primary ciliary dyskinesia. In cystic fibrosis (CF), conflicting data exist on NO levels, which are reported unexplained as either decreased or normal. Functionally, NO production in the paranasal sinuses is considered as a location-specific first-line defence mechanism. The aim of this study was to investigate the correlation between upper and lower airway NO levels and blood inflammatory parameters, CF-pathogen colonisation, and clinical data. METHODS AND FINDINGS: Nasal and bronchial NO concentrations from 57 CF patients were determined using an electrochemical analyser and correlated to pathogen colonisation of the upper and lower airways which were microbiologically assessed from nasal lavage and sputum samples. Statistical analyses were performed with respect to clinical parameters (lung function, BMI), laboratory findings (CRP, leucocytes, total-IgG, fibrinogen), and anti-inflammatory and antibiotic therapy. There were significant correlations between nasal and bronchial NO levels (rho = 0.48, p<0.001), but no correlation between NO levels and specific pathogen colonisation. In patients receiving azithromycin, significantly reduced bronchial NO and a tendency to reduced nasal NO could be found. Interestingly, a significant inverse correlation of nasal NO to CRP (rho = -0.28, p = 0.04) and to leucocytes (rho = -0.41, p = 0.003) was observed. In contrast, bronchial NO levels showed no correlation to clinical or inflammatory parameters. CONCLUSION: Given that NO in the paranasal sinuses is part of the first-line defence mechanism against pathogens, our finding of reduced nasal NO in CF patients with elevated systemic inflammatory markers indicates impaired upper airway defence. This may facilitate further pathogen acquisition in the sinonasal area, with consequences for lung colonisation and the overall outcome in CF. PMID- 24236101 TI - Hip and knee strength is not affected in 12-16 year old adolescents with patellofemoral pain--a cross-sectional population-based study. AB - BACKGROUND: One of the rationales behind using strength training in the treatment of adolescents with Patellofemoral Pain (PFP) is that reduced strength of the lower extremity is a risk factor for PFP and a common deficit. This rationale is based on research conducted on adolescents >15 years of age but has never been investigated among young adolescents with PFP. OBJECTIVES: To compare isometric muscle strength of the lower extremity among adolescents with PFP compared to age and gender-matched pain-free adolescents. METHODS: In 2011 a population-based cohort (APA2011-cohort) consisting of 768 adolescents aged 12-15 years from 8 local schools was formed. In September 2012, all adolescents who reported knee pain in September 2011 were offered a clinical examination if they still had knee pain. From these, 20 adolescents (16 females) were diagnosed with PFP. Pain-free adolescents from the APA2011-cohort (n = 20) were recruited on random basis as age- and gender-matched pairs. Primary outcome was isometric knee extension strength normalized to body weight (%BW) and blinded towards subject information. Secondary outcomes included knee flexion, hip abduction/adduction and hip internal/external rotation strength. Demographic data included Knee Injury and Osteoarthritis Outcome Score (KOOS) and symptom duration. RESULTS: Adolescents with PFP reported long symptom duration and significantly worse KOOS scores compared to pain-free adolescents. There were no significant differences in isometric knee extension strength (Delta0.3% BW, p = 0.97), isometric knee flexion strength (Delta0.4% BW, p = 0.84) or different measures of hip strength (Delta0.4 to 1.1% BW, p>0.35). CONCLUSION: Young symptomatic adolescents with PFP between 12 and 16 years of age did not have decreased isometric muscle strength of the knee and hip. These results question the rationale of targeting strength deficits in the treatment of adolescents with PFP. However, strength training may still be an effective treatment for those individuals with PFP suffering from strength deficits. PMID- 24236102 TI - Development of a specific monoclonal antibody-based ELISA to measure the artemether content of antimalarial drugs. AB - Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemether to obtain 9-hydroxyartemether, which was subsequently used to prepare a 9-O-succinylartemether hapten for conjugation with ovalbumin as the immunogen. A monoclonal antibody (mAb), designated as 2G12E1, was produced with high specificity to artemether. 2G12E1 showed low cross reactivities to dihydroartemisinin, artemisinin, artesunate and other major antimalarial drugs. An indirect competitive enzyme linked immunosorbent assay (icELISA) developed showed a concentration causing 50% of inhibition for artemether as 3.7 ng mL-1 and a working range of 0.7-19 ng mL-1. The icELISA was applied for determination of artemether content in different commercial drugs and the results were comparable to those determined by high-performance liquid chromatography analysis. In comparison with reported broad cross activity of anti-artemisinin mAbs, the most notable advantage of the 2G12E1-based ELISA is its high specificity to artemether only. PMID- 24236104 TI - Cystathionine beta-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance. AB - BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer. PMID- 24236105 TI - Enzymatic regulation of glycogenolysis in a subarctic population of the wood frog: implications for extreme freeze tolerance. AB - The wood frog, Rana sylvatica, from Interior Alaska survives freezing at -16 degrees C, a temperature 10-13 degrees C below that tolerated by its southern conspecifics. We investigated the hepatic freezing response in this northern phenotype to determine if its profound freeze tolerance is associated with an enhanced glucosic cryoprotectant system. Alaskan frogs had a larger liver glycogen reserve that was mobilized faster during early freezing as compared to conspecifics from a cool-temperate region (southern Ohio, USA). In Alaskan frogs the rapid glucose production in the first hours of freezing was associated with a 7-fold increase in glycogen phosphorylase activity above unfrozen frog levels, and the activity of this enzyme was higher than that of frozen Ohioan frogs. Freezing of Ohioan frogs induced a more modest (4-fold) increase in glycogen phosphorylase activity above unfrozen frog values. Relative to the Ohioan frogs, Alaskan frogs maintained a higher total protein kinase A activity throughout an experimental freezing/thawing time course, and this may have potentiated glycogenolysis during early freezing. We found populational variation in the activity and protein level of protein kinase A which suggested that the Alaskan population had a more efficient form of this enzyme. Alaskan frogs modulated their glycogenolytic response by decreasing the activity of glycogen phosphorylase after cryoprotectant mobilization was well under way, thereby conserving their hepatic glycogen reserve. Ohioan frogs, however, sustained high glycogen phosphorylase activity until early thawing and consumed nearly all their liver glycogen. These unique hepatic responses of Alaskan R. sylvatica likely contribute to this phenotype's exceptional freeze tolerance, which is necessary for their survival in a subarctic climate. PMID- 24236103 TI - Preconditioning of microglia by alpha-synuclein strongly affects the response induced by toll-like receptor (TLR) stimulation. AB - In recent years, it has become accepted that alpha-synuclein (alphaSyn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson's disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer's disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) alphaSyn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with alphaSyn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of alphaSyn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in alphaSyn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated alphaSyn pre sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic alpha-synuclein-related neuropathologies. PMID- 24236106 TI - Influence of cardiac decentralization on cardioprotection. AB - The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization (surgical) modulates coronary flow reserve and myocardial protection in preconditioned dogs subject to ischemia-reperfusion. Experiments were conducted on four groups of anesthetised, open-chest dogs (n = 32): 1- controls (CTR, intact cardiac nerves), 2- ischemic preconditioning (PC; 4 cycles of 5-min IR), 3- cardiac decentralization (CD) and 4- CD+PC; all dogs underwent 60-min coronary occlusion and 180-min reperfusion. Coronary blood flow and reactive hyperemic responses were assessed using a blood volume flow probe. Infarct size (tetrazolium staining) was related to anatomic area at risk and coronary collateral blood flow (microspheres) in the anatomic area at risk. Post ischemic reactive hyperemia and repayment-to-debt ratio responses were significantly reduced for all experimental groups; however, arterial perfusion pressure was not affected. Infarct size was reduced in CD dogs (18.6 +/- 4.3; p = 0.001, data are mean +/- 1 SD) compared to 25.2 +/- 5.5% in CTR dogs and was less in PC dogs as expected (13.5 +/- 3.2 vs. 25.2 +/- 5.5%; p = 0.001); after acute CD, PC protection was conserved (11.6 +/- 3.4 vs. 18.6 +/- 4.3%; p = 0.02). In conclusion, our findings provide strong evidence that myocardial protection against ischemic injury can be preserved independent of extrinsic cardiac nerve inputs. PMID- 24236108 TI - Dogs' Eavesdropping from people's reactions in third party interactions. AB - Eavesdropping involves the acquisition of information from third-party interactions, and can serve to indirectly attribute reputation to individuals. There is evidence on eavesdropping in dogs, indicating that they can develop a preference for people based on their cooperativeness towards others. In this study, we tested dogs' eavesdropping abilities one step further. In a first experiment, dogs could choose between cooperative demonstrators (the donors) who always gave food to an approaching third person (the beggar); here, the only difference between donors was whether they received positive or negative reactions from the beggar (through verbal and gestural means). Results showed that dogs preferentially approached the donor who had received positive reactions from the beggar. By contrast, two different conditions showed that neither the beggar's body gestures nor the verbal component of the interaction on their own were sufficient to affect the dogs' preferences. We also ran two further experiments to test for the possibility of dogs' choices being driven by local enhancement. When the donors switched places before the choice, dogs chose at random. Similarly, in a nonsocial condition in which donors were replaced by platforms, subjects chose at chance levels. We conclude that dogs' nonrandom choices in the present protocol relied on the simultaneous presence of multiple cues, such as the place where donors stood and several features of the beggar's behavior (gestural and verbal reactions, and eating behavior). Nonetheless, we did not find conclusive evidence that dogs discriminated the donors by their physical features, which is a prerequisite of reputation attribution. PMID- 24236107 TI - Infection of human endothelial cells by Japanese encephalitis virus: increased expression and release of soluble HLA-E. AB - Japanese encephalitis virus (JEV) is a single stranded RNA virus that infects the central nervous system leading to acute encephalitis in children. Alterations in brain endothelial cells have been shown to precede the entry of this flavivirus into the brain, but infection of endothelial cells by JEV and their consequences are still unclear. Productive JEV infection was established in human endothelial cells leading to IFN-beta and TNF-alpha production. The MHC genes for HLA-A, -B, C and HLA-E antigens were upregulated in human brain microvascular endothelial cells, the endothelial-like cell line, ECV 304 and human foreskin fibroblasts upon JEV infection. We also report the release/shedding of soluble HLA-E (sHLA-E) from JEV infected human endothelial cells for the first time. This shedding of sHLA-E was blocked by an inhibitor of matrix metalloproteinases (MMP). In addition, MMP-9, a known mediator of HLA solubilisation was upregulated by JEV. In contrast, human fibroblasts showed only upregulation of cell-surface HLA-E. Addition of UV inactivated JEV-infected cell culture supernatants stimulated shedding of sHLA-E from uninfected ECV cells indicating a role for soluble factors/cytokines in the shedding process. Antibody mediated neutralization of TNF-alpha as well as IFNAR receptor together not only resulted in inhibition of sHLA-E shedding from uninfected cells, it also inhibited HLA-E and MMP-9 gene expression in JEV-infected cells. Shedding of sHLA-E was also observed with purified TNF-alpha and IFN-beta as well as the dsRNA analog, poly (I:C). Both IFN beta and TNF-alpha further potentiated the shedding when added together. The role of soluble MHC antigens in JEV infection is hitherto unknown and therefore needs further investigation. PMID- 24236109 TI - Predictors of intelligence at the age of 5: family, pregnancy and birth characteristics, postnatal influences, and postnatal growth. AB - Parental education and maternal intelligence are well-known predictors of child IQ. However, the literature regarding other factors that may contribute to individual differences in IQ is inconclusive. The aim of this study was to examine the contribution of a number of variables whose predictive status remain unclarified, in a sample of basically healthy children with a low rate of pre- and postnatal complications. 1,782 5-year-old children sampled from the Danish National Birth Cohort (2003-2007) were assessed with a short form of the Wechsler Preschool and Primary Scale of Intelligence - Revised. Information on parental characteristics, pregnancy and birth factors, postnatal influences, and postnatal growth was collected during pregnancy and at follow-up. A model including study design variables and child's sex explained 7% of the variance in IQ, while parental education and maternal IQ increased the explained variance to 24%. Other predictors were parity, maternal BMI, birth weight, breastfeeding, and the child's head circumference and height at follow-up. These variables, however, only increased the explained variance to 29%. The results suggest that parental education and maternal IQ are major predictors of IQ and should be included routinely in studies of cognitive development. Obstetrical and postnatal factors also predict IQ, but their contribution may be of comparatively limited magnitude. PMID- 24236110 TI - A Bayesian meta-analysis on prevalence of hepatitis B virus infection among Chinese volunteer blood donors. AB - BACKGROUND: Although transfusion-transmitted infection of hepatitis B virus (HBV) threatens the blood safety of China, the nationwide circumstance of HBV infection among blood donors is still unclear. OBJECTIVES: To comprehensively estimate the prevalence of HBsAg positive and HBV occult infection (OBI) among Chinese volunteer blood donors through bayesian meta-analysis. METHODS: We performed an electronic search in Pub-Med, Web of Knowledge, Medline, Wanfang Data and CNKI, complemented by a hand search of relevant reference lists. Two authors independently extracted data from the eligible studies. Then two bayesian random effect meta-analyses were performed, followed by bayesian meta-regressions. RESULTS: 5957412 and 571227 donors were identified in HBsAg group and OBI group, respectively. The pooled prevalence of HBsAg group and OBI group among donors is 1.085% (95% credible interval [CI] 0.859%~1.398%) and 0.094% (95% CI 0.0578%~0.1655%). For HBsAg group, subgroup analysis shows the more developed area has a lower prevalence than the less developed area; meta-regression indicates there is a significant decreasing trend in HBsAg positive prevalence with sampling year (beta = -0.1202, 95% -0.2081~-0.0312). CONCLUSION: Blood safety against HBV infection in China is suffering serious threats and the government should take effective measures to improve this situation. PMID- 24236111 TI - Androgen receptor activity is affected by both nuclear matrix localization and the phosphorylation status of the heterogeneous nuclear ribonucleoprotein K in anti-androgen-treated LNCaP cells. AB - The androgen receptor (AR) plays a central role in the development and progression of prostate cancer (PCa) and anti-androgen therapy is a standard treatment. Unfortunately, after a few years, the majority of patients progress, developing androgen-independent PCa. AR-driven gene transcription recruits a large number of co-activator/co-repressor complexes; among these, the heterogeneous nuclear ribonucleoprotein K (hnRNP K) directly interacts with and regulates the AR translational apparatus. Here we examined AR and hnRNP K expression in response to the treatment of LNCaP cells with anti-androgen cyproterone acetate (CPA) or bicalutamide (BIC). AR and hnRNP K modulation and compartmentalization were studied by Western blot and confocal microscopy. Phosphate-affinity gel electrophoresis was employed to examine how anti-androgens modified hnRNP K phosphorylation. 10(-6) M CPA significantly stimulated LNCaP proliferation, whereas for 10(-4) M CPA or 10(-5) M BIC an antagonistic effect was observed. After anti-androgen treatment, AR expression was remarkably down regulated within both the cytoplasm and the nucleus; however, when CPA had an agonist activity, the AR associated with the nuclear matrix (NM) increased approximately 2.5 times. This increase was synchronous with a higher PSA expression, indicating that the NM-associated AR represents the active complex. After BIC treatment, hnRNP K expression was significantly lower in the NM, the protein was hypophosphorylated and the co-localization of AR and hnRNP K decreased. In contrast, CPA as an agonist caused hnRNP K hyperphosphorylation and an increase in the co-localization of two proteins. These findings demonstrate that, in vitro, there is a strong relationship between NM-associated AR and both cell viability and PSA levels, indicating that AR transcriptional activity is critically dependent on its subnuclear localization. Moreover, the agonistic/antagonistic activity of anti-androgens is associated with modifications in hnRNP K phosphorylation, indicating an involvement of this protein in the AR transcriptional activity and likely in the onset of the androgen-independent phenotype. PMID- 24236113 TI - Image quality characteristics of handheld display devices for medical imaging. AB - Handheld devices such as mobile phones and tablet computers have become widespread with thousands of available software applications. Recently, handhelds are being proposed as part of medical imaging solutions, especially in emergency medicine, where immediate consultation is required. However, handheld devices differ significantly from medical workstation displays in terms of display characteristics. Moreover, the characteristics vary significantly among device types. We investigate the image quality characteristics of various handheld devices with respect to luminance response, spatial resolution, spatial noise, and reflectance. We show that the luminance characteristics of the handheld displays are different from those of workstation displays complying with grayscale standard target response suggesting that luminance calibration might be needed. Our results also demonstrate that the spatial characteristics of handhelds can surpass those of medical workstation displays particularly for recent generation devices. While a 5 mega-pixel monochrome workstation display has horizontal and vertical modulation transfer factors of 0.52 and 0.47 at the Nyquist frequency, the handheld displays released after 2011 can have values higher than 0.63 at the respective Nyquist frequencies. The noise power spectra for workstation displays are higher than 1.2 * 10(-5) mm(2) at 1 mm(-1), while handheld displays have values lower than 3.7 * 10(-6) mm(2). Reflectance measurements on some of the handheld displays are consistent with measurements for workstation displays with, in some cases, low specular and diffuse reflectance coefficients. The variability of the characterization results among devices due to the different technological features indicates that image quality varies greatly among handheld display devices. PMID- 24236112 TI - Epigenetic regulation and functional characterization of microRNA-142 in mesenchymal cells. AB - The transcripts encoded by the microRNA mir-142 gene are highly active in hematopoietic cells, but expressed at low levels in many other cell types. Treatment with the demethylating agent 5-Aza-2'-deoxycytidine increased both the 1,636 nucleotide primary transcript and mature miR-142-5p/3p in mesenchymal cells, indicating that mir-142 is epigenetically repressed by DNA methylation. The transcription start site was determined to be located 1,205 base pairs upstream of the precursor sequence within a highly conserved CpG island. In addition, a second CpG island overlapped with the precursor. A TATA-box, several promoter-proximal elements and enrichment of conserved transcription factor binding sites within the first 100 base pairs upstream of the transcription start site, suggests that this region represents the core/proximal mir-142 promoter. Moreover, both CpG islands were heavily methylated in mesenchymal cells, having low levels of miR-142-5p/3p, and unmethylated in hematopoietic cells where both miRNAs were abundantly expressed. We show that treatment with 5-Aza-2' deoxycytidine significantly reduced the DNA methylation of the upstream CpG island, which led to increased expression, and that in vitro DNA methylation of the upstream region of the mir-142 precursor repressed its transcriptional activity. When overexpressed, miR-142-5p/3p reduced proliferation of cells with epigenetic silencing of endogenous mir-142. This finding is interesting as miR 142-5p/3p have been reported to be deregulated in tumors of mesenchymal origin. We provide the first experimental evidence that transcription of mir-142 is directly repressed by DNA methylation. In addition, we discovered that the antisense strand of mir-142 might act as a precursor for functional mature antisense miRNAs. Thus, our study expands the current knowledge about the regulation of mir-142 and function of miR-142-5p/3p, and adds novel insight into the rapidly increasing field of microRNA regulation. PMID- 24236115 TI - Light pollution modifies the expression of daily rhythms and behavior patterns in a nocturnal primate. AB - Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14(th) night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes. PMID- 24236114 TI - Intact lexicon running slowly--prolonged response latencies in patients with subthalamic DBS and verbal fluency deficits. AB - BACKGROUND: Verbal Fluency is reduced in patients with Parkinson's disease, particularly if treated with deep brain stimulation. This deficit could arise from general factors, such as reduced working speed or from dysfunctions in specific lexical domains. OBJECTIVE: To test whether DBS-associated Verbal Fluency deficits are accompanied by changed dynamics of word processing. METHODS: 21 Parkinson's disease patients with and 26 without deep brain stimulation of the subthalamic nucleus as well as 19 healthy controls participated in the study. They engaged in Verbal Fluency and (primed) Lexical Decision Tasks, testing phonemic and semantic word production and processing time. Most patients performed the experiments twice, ON and OFF stimulation or, respectively, dopaminergic drugs. RESULTS: Patients generally produced abnormally few words in the Verbal Fluency Task. This deficit was more severe in patients with deep brain stimulation who additionally showed prolonged response latencies in the Lexical Decision Task. Slowing was independent of semantic and phonemic word priming. No significant changes of performance accuracy were obtained. The results were independent from the treatment ON or OFF conditions. CONCLUSION: Low word production in patients with deep brain stimulation was accompanied by prolonged latencies for lexical decisions. No indication was found that the latter slowing was due to specific lexical dysfunctions, so that it probably reflects a general reduction of cognitive working speed, also evident on the level of Verbal Fluency. The described abnormalities seem to reflect subtle sequelae of the surgical procedure for deep brain stimulation rather than of the proper neurostimulation. PMID- 24236116 TI - Adherens junction formation inhibits lentivirus entry and gene transfer. AB - Although cellular signaling pathways that affect lentivirus infection have been investigated, the role of cell-cell interactions in lentiviral gene delivery remains elusive. In the course of our studies we observed that lentiviral gene transfer was a strong function of the position of epithelial cells within colonies. While peripheral cells were transduced efficiently, cells in the center of colonies were resistant to gene transfer. In addition, gene delivery was enhanced significantly under culture conditions that disrupted adherens junctions (AJ) but decreased upon AJ formation. In agreement, gene knockdown and gain-of function approaches showed that alpha-catenin, a key component of the AJ complex prevented lentivirus gene transfer. Using a doxycycline regulatable system we showed that expression of dominant negative E-cadherin enhanced gene transfer in a dose-dependent manner. In addition, dissolution of AJ by doxycycline increased entry of lentiviral particles into the cell cytoplasm in a dose-dependent manner. Taken together our results demonstrate that AJ formation renders cells non permissive to lentiviral gene transfer and may facilitate development of simple means to enhance gene delivery or combat virus infection. PMID- 24236117 TI - Social models provide a norm of appropriate food intake for young women. AB - It is often assumed that social models influence people's eating behavior by providing a norm of appropriate food intake, but this hypothesis has not been directly tested. In three experiments, female participants were exposed to a low intake model, a high-intake model, or no model (control condition). Experiments 1 and 2 used a remote-confederate manipulation and were conducted in the context of a cookie taste test. Experiment 3 used a live confederate and was conducted in the context of a task during which participants were given incidental access to food. Participants also rated the extent to which their food intake was influenced by a variety of factors (e.g., hunger, taste, how much others ate). In all three experiments, participants in the low-intake conditions ate less than did participants in the high-intake conditions, and also reported a lower perceived norm of appropriate intake. Furthermore, perceived norms of appropriate intake mediated the effects of the social model on participants' food intake. Despite the observed effects of the social models, participants were much more likely to indicate that their food intake was influenced by taste and hunger than by the behavior of the social models. Thus, social models appear to influence food intake by providing a norm of appropriate eating behavior, but people may be unaware of the influence of a social model on their behavior. PMID- 24236118 TI - B-type natriuretic peptide and prognosis of end-stage renal disease: a meta analysis. AB - BACKGROUND: The prognostic importance of B-type natriuretic peptide (BNP) or N terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively. CONCLUSIONS/SIGNIFICANCE: BNP/NT-proBNP is a promising prognostic tool to risk stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors. PMID- 24236119 TI - Estrogen receptor alpha functions in the regulation of motivation and spatial cognition in young male rats. AB - Estrogenic functions in regulating behavioral states such as motivation, mood, anxiety, and cognition are relatively well documented in female humans and animals. In males, however, although the entire enzymatic machinery for producing estradiol and the corresponding receptors are present, estrogenic functions have been largely neglected. Therefore, and as a follow-up study to previous research, we sub-chronically applied a specific estrogen receptor alpha (ERalpha) antagonist in young male rats before and during a spatial learning task (holeboard). The male rats showed a dose-dependent increase in motivational, but not cognitive, behavior. The expression of hippocampal steroid receptor genes, such as glucocorticoid (GR), mineralocorticoid (MR), androgen (AR), and the estrogen receptor ERalpha but not ERbeta was dose-dependently reduced. The expression of the aromatase but not the brain-derived neurotrophic factor (BDNF) encoding gene was also suppressed. Reduced gene expression and increased behavioral performance converged at an antagonist concentration of 7.4 umol. The hippocampal and blood serum hormone levels (corticosterone, testosterone, and 17beta-estradiol) did not differ between the experimental groups and controls. We conclude that steroid receptors (and BDNF) act in a concerted, network-like manner to affect behavior and mutual gene expression. Therefore, the isolated view on single receptor types is probably insufficient to explain steroid effects on behavior. The steroid network may keep motivation in homeostasis by supporting and constraining the behavioral expression of motivation. PMID- 24236120 TI - Subfossil leaves reveal a new upland hardwood component of the pre-European Piedmont landscape,Lancaster County, Pennsylvania. AB - Widespread deforestation, agriculture, and construction of milldams by European settlers greatly influenced valley-bottom stream morphology and riparian vegetation in the northeastern USA. The former broad, tussock-sedge wetlands with small, anastomosing channels were converted into today's incised, meandering streams with unstable banks that support mostly weedy, invasive vegetation. Vast accumulations of fine-grained "legacy" sediments that blanket the regional valley bottom Piedmont landscape now are being reworked from stream banks, significantly impairing the ecological health of downstream water bodies, most notably the Chesapeake Bay. However, potential restoration is impaired by lack of direct knowledge of the pre-settlement riparian and upslope floral ecosystems. We studied the subfossil leaf flora of Denlingers Mill, an obsolete (breached) milldam site in southeastern Pennsylvania that exhibits a modern secondary forest growing atop thin soils, above bedrock outcrops immediately adjacent to a modified, incised stream channel. Presumably, an overhanging old-growth forest also existed on this substrate until the early 1700s and was responsible for depositing exceptionally preserved, minimally transported subfossil leaves into hydric soil strata, which immediately underlie post-European settlement legacy sediments. We interpret the eleven identified species of the subfossil assemblage to primarily represent a previously unknown, upland Red Oak-American Beech mixed hardwood forest. Some elements also appear to belong to a valley-margin Red Maple Black Ash swamp forest, consistent with preliminary data from a nearby site. Thus, our results add significantly to a more complete understanding of the pre European settlement landscape, especially of the hardwood tree flora. Compared with the modern forest, it is apparent that both lowland and upslope forests in the region have been modified significantly by historical activities. Our study underscores that generally overlooked subfossil leaves can provide important, local, temporally constrained paleoecological data, with much potential value in this case for stream and wetland restoration decisions in the mid-Atlantic region. PMID- 24236121 TI - Trends in high-risk sexual behaviors among general population groups in China: a systematic review. AB - BACKGROUND: The objective of this review was to investigate whether Chinese population groups that do not belong to classical high risk groups show an increasing trend of engaging in high-risk sexual behaviors. METHODS: We systematically searched the English and Chinese literature on sexual risk behaviors published between January 1980 and March 2012 in PubMed and the China National Knowledge Infrastructure (CNKI). We included observational studies that focused on population groups other than commercial sex workers (CSWs) and their clients, and men who have sex with men (MSM) and quantitatively reported one of the following indicators of recent high-risk sexual behavior: premarital sex, commercial sex, multiple sex partners, condom use or sexually transmitted infections (STIs). We used generalized linear mixed model to examine the time trend in engaging in high-risk sexual behaviors. RESULTS: We included 174 observational studies involving 932,931 participants: 55 studies reported on floating populations, 73 on college students and 46 on other groups (i.e. out-of school youth, rural residents, and subjects from gynecological or obstetric clinics and premarital check-up centers). From the generalized linear mixed model, no significant trends in engaging in high-risk sexual behaviors were identified in the three population groups. DISCUSSION: Sexual risk behaviors among certain general population groups have not increased substantially. These groups are therefore unlikely to incite a STI/HIV epidemic among the general Chinese population. Because the studied population groups are not necessarily representative of the general population, the outcomes found may not reflect those of the general population. PMID- 24236122 TI - Lipopolysaccharide induces degradation of connexin43 in rat astrocytes via the ubiquitin-proteasome proteolytic pathway. AB - The astrocytic syncytium plays a critical role in maintaining the homeostasis of the brain through the regulation of gap junction intercellular communication (GJIC). Changes to GJIC in response to inflammatory stimuli in astrocytes may have serious effects on the brain. We have previously shown that lipopolysaccharide (LPS) reduces connexin43 (Cx43) expression and GJIC in cultured rat astrocytes via a toll-like receptor 4-mediated signaling pathway. In the present study, treatment of astrocytes with LPS resulted in a significant increase in levels of the phosphorylated forms of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) -1, -2, and -3 for up to 18 h. An increase in nuclear transcription factor NF-kappaB levels was also observed after 8 h of LPS treatment and was sustained for up to 18 h. The LPS-induced decrease in Cx43 protein levels and inhibition of GJIC were blocked by the SAPK/JNK inhibitor SP600125, but not by the NF-kappaB inhibitor BAY11-7082. Following blockade of de novo protein synthesis by cycloheximide, LPS accelerated Cx43 degradation. Moreover, the LPS-induced downregulation of Cx43 was blocked following inhibition of 26S proteasome activity using the reversible proteasome inhibitor MG132 or the irreversible proteasome inhibitor lactacystin. Immunoprecipitation analyses revealed an increased association of Cx43 with both ubiquitin and E3 ubiquitin ligase Nedd4 in astrocytes after LPS stimulation for 6 h and this effect was prevented by SP600125. Taken together, these results suggest that LPS stimulation leads to downregulation of Cx43 expression and GJIC in rat astrocytes by activation of SAPK/JNK and the ubiquitin-proteasome proteolytic pathway. PMID- 24236123 TI - Characteristics of polygalacturonate lyase C from Bacillus subtilis 7-3-3 and its synergistic action with PelA in enzymatic degumming. AB - An alkaline polygalacturonate lyase (PGL) from Bacillus subtilis 7-3-3, PelC, with diverse depolymerization abilities for different pectin substrates was found. The PGL activity of PelC decreased with increasing degree of methyl esterification of the substrate. PelA and PelC displayed notable synergistic effects in the enzymatic degumming of ramie fibers. Gum loss rates increased by 62% when PelC was used to replace up to three-eighths of the PelA dose (PelC, 60 U g(-1) ramie fibers). To the best of our knowledge, this study is the first to report the synergistic action of members of polysaccharide lyase families 1 and 3, represented by PelA and PelC, respectively. The present paper provides new insights into the improvement and production of enzymes used in enzymatic degumming. PMID- 24236124 TI - Male killing Spiroplasma preferentially disrupts neural development in the Drosophila melanogaster embryo. AB - Male killing bacteria such as Spiroplasma are widespread pathogens of numerous arthropods including Drosophila melanogaster. These maternally transmitted bacteria can bias host sex ratios toward the female sex in order to 'selfishly' enhance bacterial transmission. However, little is known about the specific means by which these pathogens disrupt host development in order to kill males. Here we show that a male-killing Spiroplasma strain severely disrupts nervous tissue development in male but not female D. melanogaster embryos. The neuroblasts, or neuron progenitors, form properly and their daughter cells differentiate into neurons of the ventral nerve chord. However, the neurons fail to pack together properly and they produce highly abnormal axons. In contrast, non-neural tissue, such as mesoderm, and body segmentation appear normal during this time, although the entire male embryo becomes highly abnormal during later stages. Finally, we found that Spiroplasma is altogether absent from the neural tissue but localizes within the gut and the epithelium immediately surrounding the neural tissue, suggesting that the bacterium secretes a toxin that affects neural tissue development across tissue boundaries. Together these findings demonstrate the unique ability of this insect pathogen to preferentially affect development of a specific embryonic tissue to induce male killing. PMID- 24236125 TI - MDR-ER: balancing functions for adjusting the ratio in risk classes and classification errors for imbalanced cases and controls using multifactor dimensionality reduction. AB - BACKGROUND: Determining the complex relationship between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has proven capable of effectively detecting statistical patterns of epistasis. However, MDR has its weakness in accurately assigning multi-locus genotypes to either high-risk and low-risk groups, and does generally not provide accurate error rates when the case and control data sets are imbalanced. Consequently, results for classification error rates and odds ratios (OR) may provide surprising values in that the true positive (TP) value is often small. METHODOLOGY/PRINCIPAL FINDINGS: To address this problem, we introduce a classifier function based on the ratio between the percentage of cases in case data and the percentage of controls in control data to improve MDR (MDR-ER) for multi-locus genotypes to be classified correctly into high-risk and low-risk groups. In this study, a real data set with different ratios of cases to controls (1:4) was obtained from the mitochondrial D-loop of chronic dialysis patients in order to test MDR-ER. The TP and TN values were collected from all tests to analyze to what degree MDR-ER performed better than MDR. CONCLUSIONS/SIGNIFICANCE: Results showed that MDR-ER can be successfully used to detect the complex associations in imbalanced data sets. PMID- 24236126 TI - Monitoring escape and feeding behaviours of cruiser fish by inertial and magnetic sensors. AB - A method was developed and applied for monitoring two types of fast-start locomotion (feeding and escape) of a cruiser fish, Japanese amberjacks Seriola quinqueradiata. A data logger, which incorporated a 3-axis gyroscope, a 3-axis accelerometer and a 3-axis magnetometer, was attached to the five fish. The escape, feeding and routine movements of the fish, which were triggered in tank experiments, were then recorded by the data logger and video cameras. The locomotor variables, calculated based on the high resolution measurements by the data logger (500 Hz), were investigated to accurately detect and classify the types of fast-track behaviour. The results show that fast-start locomotion can be detected with a high precision (0.97) and recall rate (0.96) from the routine movements. Two types of fast-start movements were classified with high accuracy (0.84). Accuracy was greater if the data were obtained from the data logger, which combined an accelerometer, a gyroscope and a magnetometer, than if only an accelerometer (0.80) or a gyroscope (0.66) was used. PMID- 24236127 TI - The impact of cost and network topology on urban mobility: a study of public bicycle usage in 2 U.S. cities. AB - Understanding the drivers of urban mobility is vital for epidemiology, urban planning, and communication networks. Human movements have so far been studied by observing people's positions in a given space and time, though most recent models only implicitly account for expected costs and returns for movements. This paper explores the explicit impact of cost and network topology on mobility dynamics, using data from 2 city-wide public bicycle share systems in the USA. User mobility is characterized through the distribution of trip durations, while network topology is characterized through the pairwise distances between stations and the popularity of stations and routes. Despite significant differences in station density and physical layout between the 2 cities, trip durations follow remarkably similar distributions that exhibit cost sensitive trends around pricing point boundaries, particularly with long-term users of the system. Based on the results, recommendations for dynamic pricing and incentive schemes are provided to positively influence mobility patterns and guide improved planning and management of public bicycle systems to increase uptake. PMID- 24236128 TI - Directional coordination of thumb and finger forces during precision pinch. AB - The human opposable thumb enables the hand to perform dexterous manipulation of objects, which requires well-coordinated digit force vectors. This study investigated the directional coordination of force vectors generated by the thumb and index finger during precision pinch. Fourteen right-handed, healthy subjects were instructed to exert pinch force on an externally stabilized apparatus with the pulps of the thumb and index finger. Subjects applied forces to follow a force-ramp profile that linearly increased from 0 to 12 N and then decreased to 0 N, at a rate of +/- 3 N/s. Directional relationships between the thumb and index finger force vectors were quantified using the coordination angle (CA) between the force vectors. Individual force vectors were further analyzed according to their projection angles (PAs) with respect to the pinch surface planes and the shear angles (SAs) within those planes. Results demonstrated that fingertip force directions were dependent on pinch force magnitude, especially at forces below 2 N. Hysteresis was observed in the force-CA relationship for increasing and decreasing forces and fitted with exponential models. The fitted asymptotic values were 156.0 +/- 6.6 degrees and 150.8 +/- 9.3 degrees for increasing and decreasing force ramps, respectively. The PA of the thumb force vector deviated further from the direction perpendicular to the pinching surface planes than that of the index finger. The SA showed that the index finger force vector deviated in the ulnar-proximal direction, whereas the thumb switched its force between the ulnar-proximal and radial-proximal directions. The findings shed light on the effects of anatomical composition, biomechanical function, and neuromuscular control in coordinating digit forces during precision pinch, and provided insight into the magnitude-dependent force directional control which potentially affects a range of dexterous manipulations. PMID- 24236129 TI - Diet-induced obesity reduces the responsiveness of the peripheral taste receptor cells. AB - INTRODUCTION: Obesity is a growing epidemic that causes many serious health related complications. While the causes of obesity are complex, there is conclusive evidence that overconsumption coupled with a sedentary lifestyle is the primary cause of this medical condition. Dietary consumption is controlled by appetite which is in turn regulated by multiple neuronal systems, including the taste system. However, the relationship between taste and obesity has not been well defined. Growing evidence suggests that taste perception in the brain is altered in obese animals and humans, however no studies have determined if there are altered taste responses in the peripheral taste receptor cells, which is the initiation site for the detection and perception of taste stimuli. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used C57Bl/6 mice which readily become obese when placed on a high fat diet. After ten weeks on the high fat diet, we used calcium imaging to measure how taste-evoked calcium signals were affected in the obese mice. We found that significantly fewer taste receptor cells were responsive to some appetitive taste stimuli while the numbers of taste cells that were sensitive to aversive taste stimuli did not change. Properties of the taste-evoked calcium signals were also significantly altered in the obese mice. Behavioral analyses found that mice on the high fat diet had reduced ability to detect some taste stimuli compared to their littermate controls. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that diet-induced obesity significantly influences peripheral taste receptor cell signals which likely leads to changes in the central taste system and may cause altered taste perception. PMID- 24236130 TI - Evaluation of the combined application of ultrasound imaging techniques for middle cerebral artery stent surveillance and follow-up study. AB - OBJECTIVE: In recent years, cerebral artery stenting has become an effective method for the treatment of cerebral artery stenosis. However, methods for assessing efficacy and techniques for follow-up imaging still need to be developed. This study was designed to evaluate the application of transcranial color-coded sonography (TCCS) in assessing stenting of middle cerebral artery (MCA) stenosis. And, two new imaging techniques (vascular enhancement technology (VET) and 3-dimensional (3D) imaging) were tried out and evaluated. METHOD: We enrolled 43 patients with cerebral artery stenosis for vascular stent implantation. All patients were examined by ultrasonography and confirmed through digital subtraction angiography. The stenosis was imaged and blood flow parameters were analyzed before and after the procedure using TCCS. VET and 3D imaging model were used in part of the patients. Important postoperative hemodynamic changes were noted. RESULTS: 1) Adequate stent image was present in 41 out of 43 patients as detected by postoperative 2-dimensional imaging. Images lacking clarity were obtained in 2 patients. 2) The perioperative and postoperative (one week follow-up) instantaneous blood flow velocity at the site of stenosis was significantly decreased (P<0.05) when compared with preoperative levels. Differences between postoperative (one week follow-up) and preoperative blood flow velocity were significant (P<0.05). Differences in blood flow velocity at long-term follow-up (six months and two years) compared to one-week values were not statistically significant (P>0.05). 3) VET imaging visualizes the MCA lumen and stent morphology clearly. 3D ultrasound can be used for imaging of the stent shape as well as its inner surface. CONCLUSION: TCCD can be considered a quick and effective clinical detection method to evaluate the intracranial arterial hemodynamics changes before and after stenting treatment for MCA stenosis. New imaging technologies 3D and VET can achieve additional image information. PMID- 24236131 TI - Comparisons of the efficacy of alpha glucosidase inhibitors on type 2 diabetes patients between Asian and Caucasian. AB - BACKGROUND: To compare the efficacy of glycemic control and insulin secretion of alpha glucosidase inhibitors (AGI) on type 2 diabetes patients between Asian and Caucasian. METHODOLOGY/PRINCIPAL FINDINGS: The MEDLINE(r), EMBASE(r), CENTRAL were searched and qualified studies in Asian and Caucasian population comparing AGI treatment with placebo or other oral anti-diabetic drugs in type 2 diabetic patients were included. Totally 58 qualified studies were included. When AGI treatment was compared with placebo, a significant difference in HbA1c decline from baseline favoring AGI treatment was found in Asian (weighted mean difference (WMD), -0.50%; 95% CI, -0.66% to -0.34%) and in Caucasian a significant difference in HbA1c decline favoring AGI treatment was also found (WMD, -0.68%; 95% CI, -0.76% to -0.60%). In Asian, fasting plasma glucose was reduced with AGI treatment compared with placebo (WMD, -0.53 mmol/L; 95% CI, -0.91 to -0.14 mmol/L) and in Caucasian there was also a significant difference in FPG changes favoring AGI therapy (WMD, -0.88 mmol/L; 95% CI, -1.00 to -0.77 mmol/L). Studies in Asian showed a significant difference in fasting insulin changes favoring AGI treatment (WMD, -0.78 uU/ml; 95% CI, -0.96 to -0.59 uU/ml). While in Caucasian fasting insulin was decreased without significance with AGI treatment (WMD-1.24 uU/ml; 95% CI, -2.51 to 0.04 uU/ml). Body weight was decreased with AGI treatment in Asian (WMD, -1.00 kg; 95% CI, -1.69 to -0.31 kg) and was also decreased with AGI treatment in Caucasian (WMD, -0.73 kg; 95% CI, -1.13 to -0.33 kg). CONCLUSIONS/SIGNIFICANCE: According to results from this meta-analysis, the efficacy in glucose lowering, body weight reduction and insulin secretion decreasing of AGI treatment in Asian were comparable with those in Caucasian. PMID- 24236132 TI - Vertical profiles of bacteria in the tropical and subarctic oceans revealed by pyrosequencing. AB - Community composition of Bacteria in the surface and deep water layers were examined at three oceanic sites in the Pacific Ocean separated by great distance, i.e., the South China Sea (SCS) in the western tropical Pacific, the Costa Rica Dome (CRD) in the eastern tropical Pacific and the western subarctic North Pacific (SNP), using high throughput DNA pyrosequencing of the 16S rRNA gene. Bioinformatic analysis rendered a total of 143600 high quality sequences with an average 11967 sequences per sample and mean read length of 449 bp. Phylogenetic analysis showed that Proteobacteria dominated in all shallow and deep waters, with Alphaproteobacteria and Gammaproteobacteria the two most abundant components, and SAR11 the most abundant group at family level in all regions. Cyanobacteria occurred mainly in the surface euphotic layer, and the majority of them in the tropical waters belonged to the GpIIa family including Prochlorococcus and Synechococcus, whilst those associated with Cryptophytes and diatoms were common in the subarctic waters. In general, species richness (Chao1) and diversity (Shannon index H') were higher for the bacterial communities in the intermediate water layers than for those in surface and deep waters. Both NMDS plot and UPGMA clustering demonstrated that bacterial community composition in the deep waters (500 m ~2000 m) of the three oceanic regions shared a high similarity and were distinct from those in the upper waters (5 m ~100 m). Our study indicates that bacterial community composition in the DOC-poor deep water in both tropical and subarctic regions were rather stable, contrasting to those in the surface water layers, which could be strongly affected by the fluctuations of environmental factors. PMID- 24236133 TI - Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake. AB - Polychlorinated biphenyls (PCBs) are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR) has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs) using the mammalian pregnane X receptor (PXR). In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR) were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants. PMID- 24236134 TI - Breastfeeding and its prospective association with components of the GH-IGF-Axis, insulin resistance and body adiposity measures in young adulthood--insights from linear and quantile regression analysis. AB - BACKGROUND: Breastfeeding may lower chronic disease risk by long-term effects on hormonal status and adiposity, but the relations remain uncertain. OBJECTIVE: To prospectively investigate the association of breastfeeding with the growth hormone- (GH) insulin-like growth factor- (IGF) axis, insulin sensitivity, body composition and body fat distribution in younger adulthood (18-37 years). DESIGN: Data from 233 (54% female) participants of a German cohort, the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, with prospective data on infant feeding were analyzed. Multivariable linear as well as quantile regression were performed with full breastfeeding (not: <= 2, short: 3 17, long: >17 weeks) as exposure and adult IGF-I, IGF binding proteins (IGFBP) 1, -2, -3, homeostasis model assessment of insulin resistance (HOMA-IR), fat mass index, fat-free mass index, and waist circumference as outcomes. RESULTS: After adjustment for early life and socio-economic factors, women who had been breastfed longer displayed higher adult IGFBP-2 (p(trend) = 0.02) and lower values of HOMA-IR (p(trend) = 0.004). Furthermore, in women breastfeeding duration was associated with a lower mean fat mass index (p(trend) = 0.01), fat free mass index (p(trend) = 0.02) and waist circumference (p(trend) = 0.004) in young adulthood. However, there was no relation to IGF-I, IGFBP-1 and IGFBP-3 (all p(trend) > 0.05). Associations for IGFBP-2 and fat mass index were more pronounced at higher, for waist circumference at very low or high percentiles of the distribution. In men, there was no consistent relation of breastfeeding with any outcome. CONCLUSIONS: Our data suggest that breastfeeding may have long-term, favorable effects on extremes of adiposity and insulin metabolism in women, but not in men. In both sexes, breastfeeding does not seem to induce programming of the GH-IGF-axis. PMID- 24236135 TI - Plasma concentrations predict aortic expression of growth-arrest-specific protein 6 in patients undergoing coronary artery bypass grafting. AB - AIMS: The tyrosine kinase receptor Axl is expressed in the vasculature, and growth arrest-specific protein 6 (Gas6) is its ligand. Plasma Gas6 levels have been shown to be associated with endothelial dysfunction markers and cardiovascular events. We set out to determine the plasma Gas6 levels in patients undergoing coronary artery bypass grafting (CABG) and investigate the expression of Gas6 and Axl in the aorta. METHODS AND RESULTS: Immunoassays were used to investigate plasma Gas6 levels in CABG patients (n = 19) and control subjects (n = 20). The expression of Gas6 and Axl in the injured aorta were examined by reverse transcription-polymerase chain reactions, real-time reverse transcription polymerase chain reactions, western blotting, and immunohistochemical staining. Plasma Gas6 levels were significantly lower in CABG patients than in matched control subjects. In CABG patients, plasma Gas6 levels were negatively correlated with fasting glucose, E-selectin, and vascular cell adhesion molecule-1 levels. The levels predicted the operative mortality rate and were positively correlated with plasma soluble Axl (sAxl) levels and Gas6 expression in the aorta. Moreover, Gas6 expression was positively correlated with Axl expression in the aorta. CONCLUSION: We concluded that plasma Gas6 is associated with fasting glucose, endothelial dysfunction markers, sAxl values, and vascular Gas6 expression in CABG patients, and it predicts the operative mortality of these patients. These findings suggest that the Gas6/Axl system is crucial in vascular biology. PMID- 24236136 TI - Copper promotes TFF1-mediated Helicobacter pylori colonization. AB - The trefoil peptides (TFF1, TFF2 and TFF3) are a family of small highly conserved proteins that play an essential role in epithelial regeneration within the gastrointestinal tract, where they are mainly expressed. TFF1 expression is strongly induced after mucosal injury and it has been proposed that tff1 functions as a gastric tumor suppressor gene. Several studies confirm that tff1 expression is frequently lost in gastric cancer because of deletions, mutations or methylation of the tff1 promoter. Infection by Helicobacter pylori (H. pylori) results in chronic gastritis and it can lead to the development of gastric or duodenal ulcers. Moreover, it is known that there is a strong link to the development of gastric cancer. It has been shown that H. pylori interacts with the dimeric form of TFF1 and that the rough form of lipopolysaccharide mediates this interaction. We have previously reported that the carboxy-terminus of TFF1 is able to specifically bind copper ions (Cu) and that Cu binding favours the homodimerization of the peptide, thus enhancing its motogenic activity. Here, we report that the Cu-TFF1 cuprocomplex promotes adherence of H. pylori to epithelial cells. Adherence of H. pylori to gastric adenocarcinoma cells, AGS AC1 cells, induced to hyper-express TFF1 was enhanced compared to noninduced cells. Copper further promoted this interaction. A H. pylori mutant unable to bind TFF1 did not show enhanced infection of induced cells. Cu treatment induced a thickening of the mucus layer produced by the colorectal adenocarcinoma mucus secreting, goblet cells, HT29-E12 and promoted H. pylori colonisation. Finally, SPR analysis shows that the C-terminus of TFF1, involved in the binding of copper, is also able to selectively bind H. pylori RF-LPS. PMID- 24236137 TI - Public health response systems in-action: learning from local health departments' experiences with acute and emergency incidents. AB - As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems. PMID- 24236139 TI - Good days, bad days: wind as a driver of foraging success in a flightless seabird, the southern rockhopper penguin. AB - Due to their restricted foraging range, flightless seabirds are ideal models to study the short-term variability in foraging success in response to environmentally driven food availability. Wind can be a driver of upwelling and food abundance in marine ecosystems such as the Southern Ocean, where wind regime changes due to global warming may have important ecological consequences. Southern rockhopper penguins (Eudyptes chrysocome) have undergone a dramatic population decline in the past decades, potentially due to changing environmental conditions. We used a weighbridge system to record daily foraging mass gain (the difference in mean mass of adults leaving the colony in the morning and returning to the colony in the evening) of adult penguins during the chick rearing in two breeding seasons. We related the day-to-day variability in foraging mass gain to ocean wind conditions (wind direction and wind speed) and tested for a relationship between wind speed and sea surface temperature anomaly (SSTA). Foraging mass gain was highly variable among days, but did not differ between breeding seasons, chick rearing stages (guard and creche) and sexes. It was strongly correlated between males and females, indicating synchronous changes among days. There was a significant interaction of wind direction and wind speed on daily foraging mass gain. Foraging mass gain was highest under moderate to strong winds from westerly directions and under weak winds from easterly directions, while decreasing under stronger easterly winds and storm conditions. Ocean wind speed showed a negative correlation with daily SSTA, suggesting that winds particularly from westerly directions might enhance upwelling and consequently the prey availability in the penguins' foraging areas. Our data emphasize the importance of small-scale, wind-induced patterns in prey availability on foraging success, a widely neglected aspect in seabird foraging studies, which might become more important with increasing changes in climatic variability. PMID- 24236138 TI - Cognitive impairment, depression, comorbidity of the two and associated factors among the early sixties in a rural Korean community. AB - This study was conducted to investigate the prevalence of cognitive impairment, depression, and comorbidity of the two conditions and related factors in subjects aged in early 60s. This cross-sectional study included 3,174 inhabitants aged 60 64 years old in a rural area of Korea. Cognitive function was evaluated by the Korean version of the Mini-Mental State Examination (MMSE-K), and depression was measured using the short form of the Geriatric Depression Scale (GDS-15). The overall prevalence of cognitive impairment (MMSE-K <= 24) was 17.4%, that of depression was 26.0% (GDS-15 >= 8), and the co-morbidity was 7.1%. Female gender, living with one housemate, and high GDS-15 score were significantly associated with increased cognitive impairment. Employment status and more years of schooling were associated with a decreased probability of cognitive impairment. Increased depression was significantly associated with bereavement and receiving benefits from the Medical Aid Program. Employed status, more years of schooling, and higher MMSE-K scores were significantly associated with decreased depression. The risk of comorbidity was associated with bereavement and receipt of Medical Aid benefits (odds ratio[OR], 1.85; 95% confidence interval[CI], 1.26-2.71; OR, 5.02; 95% CI, 2.37-10.63; respectively). Employment and more years of schooling were associated with a lower risk of comorbidity (OR, 0.46; 95% CI, 0.34-0.62, P trend <0.01). The correlated factors for cognitive impairment, depression, and comorbidity of the two conditions were similar, and employment status and years of schooling were associated with all three conditions. PMID- 24236140 TI - Using effort to measure reward value of faces in children with autism. AB - According to one influential account, face processing atypicalities in autism reflect reduced reward value of faces, which results in limited attention to faces during development and a consequent failure to acquire face expertise. Surprisingly, however, there is a paucity of work directly investigating the reward value of faces for individuals with autism and the evidence for diminished face rewards in this population remains equivocal. In the current study, we measured how hard children with autism would work to view faces, using an effortful key-press sequence, and whether they were sensitive to the differential reward value of attractive and unattractive faces. Contrary to expectations, cognitively able children with autism did not differ from typically developing children of similar age and ability in their willingness to work to view faces. Moreover, the effort expended was strongly positively correlated with facial attractiveness ratings in both groups of children. There was also no evidence of atypical reward values for other, less social categories (cars and inverted faces) in the children with autism. These results speak against the possibility that face recognition difficulties in autism are explained by atypical reward value of faces. PMID- 24236141 TI - A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson's disease. AB - BACKGROUND: Psychopharmacotherapy currently constitutes the first-line treatment for depression and anxiety in Parkinson's disease (PD) however the efficacy of antidepressant treatments in PD is unclear. Several alternative treatments have been suggested as potentially more viable alternatives including dopamine agonists, repetitive transcranial magnetic stimulation, and cognitive behavioural therapy (CBT). METHOD: A meta-analysis of randomised placebo-controlled trials for depression and/or anxiety in PD was conducted to systematically examine the efficacy of current treatments for depression and anxiety in PD. RESULTS: Nine trials were included. There was only sufficient data to calculate a pooled effect for antidepressant therapies. The pooled effect of antidepressants for depression in PD was moderate but non-significant (d = .71, 95% CI = -1.33 to 3.08). The secondary effect of antidepressants on anxiety in PD was large but also non significant (d = 1.13, 95% CI = -.67 to 2.94). Two single-trials of non pharmacological treatments for depression in PD resulted in significant large effects; Omega-3 supplementation (d = .92, 95% CI = .15 to 1.69) and CBT (d = 1.57, 95% CI = 1.06 to 2.07), and warrant further exploration. CONCLUSIONS: There remains a lack of controlled trials for both pharmacological and non pharmacological treatments for depression and anxiety in PD which limits the conclusions which can be drawn. While the pooled effects of antidepressant therapies in PD were non-significant, the moderate to large magnitude of each pooled effect is promising. Non-pharmacological approaches show potential for depression in PD however more research is required. PMID- 24236142 TI - Evaluation of the appropriate perioperative antibiotic prophylaxis in Italy. AB - BACKGROUND: The appropriate use of antibiotics prophylaxis in the prevention and reduction in the incidence of surgical site infection is widespread. This study evaluates the appropriateness of the prescription of antibiotics prophylaxis prior to surgery amongst hospitalized patients in the geographic area of Avellino, Caserta, and Naples (Italy) and the factors associated with a poor adherence. METHODS: A sample of 382 patients admitted to 23 surgical wards and undergoing surgery in five hospitals were randomly selected. RESULTS: Perioperative antibiotic prophylaxis was appropriate in 18.1% of cases. The multivariate logistic regression analysis showed that patients with hypoalbuminemia, with a clinical infection, with a wound clean were more likely to receive an appropriate antibiotic prophylaxis. Compared with patients with an American Society of Anesthesiologists (ASA) score >=4, those with a score of 2 were correlated with a 64% reduction in the odds of having an appropriate prophylaxis. The appropriateness of the timing of prophylactic antibiotic administration was observed in 53.4% of the procedures. Multivariate logistic regression model showed that such appropriateness was more frequent in older patients, in those admitted in general surgery wards, in those not having been underwent an endoscopic surgery, in those with a higher length of surgery, and in patients with ASA score 1 when a score >=4 was chosen as the reference category. The most common antibiotics used inappropriately were ceftazidime, sultamicillin, levofloxacin, and teicoplanin. CONCLUSIONS: Educational interventions are needed to improve perioperative appropriate antibiotic prophylaxis. PMID- 24236143 TI - Low 2D:4D values are associated with video game addiction. AB - Androgen-dependent signaling regulates the growth of the fingers on the human hand during embryogenesis. A higher androgen load results in lower 2D:4D (second digit to fourth digit) ratio values. Prenatal androgen exposure also impacts brain development. 2D:4D values are usually lower in males and are viewed as a proxy of male brain organization. Here, we quantified video gaming behavior in young males. We found lower mean 2D:4D values in subjects who were classified according to the CSAS-II as having at-risk/addicted behavior (n = 27) compared with individuals with unproblematic video gaming behavior (n = 27). Thus, prenatal androgen exposure and a hyper-male brain organization, as represented by low 2D:4D values, are associated with problematic video gaming behavior. These results may be used to improve the diagnosis, prediction, and prevention of video game addiction. PMID- 24236144 TI - Diet reconstruction and resource partitioning of a Caribbean marine mesopredator using stable isotope bayesian modelling. AB - The trophic ecology of epibenthic mesopredators is not well understood in terms of prey partitioning with sympatric elasmobranchs or their effects on prey communities, yet the importance of omnivores in community trophic dynamics is being increasingly realised. This study used stable isotope analysis of (15)N and (13)C to model diet composition of wild southern stingrays Dasyatis americana and compare trophic niche space to nurse sharks Ginglymostoma cirratum and Caribbean reef sharks Carcharhinus perezi on Glovers Reef Atoll, Belize. Bayesian stable isotope mixing models were used to investigate prey choice as well as viable Diet Tissue Discrimination Factors for use with stingrays. Stingray delta(15)N values showed the greatest variation and a positive relationship with size, with an isotopic niche width approximately twice that of sympatric species. Shark species exhibited comparatively restricted delta(15)N values and greater delta(13)C variation, with very little overlap of stingray niche space. Mixing models suggest bivalves and annelids are proportionally more important prey in the stingray diet than crustaceans and teleosts at Glovers Reef, in contrast to all but one published diet study using stomach contents from other locations. Incorporating gut contents information from the literature, we suggest diet tissue discrimination factors values of Delta(15)N ~ 2.70/00 and Delta(13)C ~ 0.90/00 for stingrays in the absence of validation experiments. The wide trophic niche and lower trophic level exhibited by stingrays compared to sympatric sharks supports their putative role as important base stabilisers in benthic systems, with the potential to absorb trophic perturbations through numerous opportunistic prey interactions. PMID- 24236145 TI - "Fish-in-net", a novel method for cell immobilization of Zymomonas mobilis. AB - BACKGROUND: Inorganic mesoporous materials exhibit good biocompatibility and hydrothermal stability for cell immobilization. However, it is difficult to encapsulate living cells under mild conditions, and new strategies for cell immobilization are needed. We designed a "fish-in-net" approach for encapsulation of enzymes in ordered mesoporous silica under mild conditions. The main objective of this study is to demonstrate the potential of this approach in immobilization of living cells. METHODOLOGY/PRINCIPAL FINDINGS: Zymomonas mobilis cells were encapsulated in mesoporous silica-based materials under mild conditions by using a "fish-in-net" approach. During the encapsulation process, polyethyleneglycol was used as an additive to improve the immobilization efficiency. After encapsulation, the pore size, morphology and other features were characterized by various methods, including scanning electron microscopy, nitrogen adsorption desorption analysis, transmission electron microscopy, fourier transform infrared spectroscopy, and elemental analysis. Furthermore, the capacity of ethanol production by immobilized Zymomonas mobilis and free Zymomonas mobilis was compared. CONCLUSIONS/SIGNIFICANCE: In this study, Zymomonas mobilis cells were successfully encapsulated in mesoporous silica-based materials under mild conditions by the "fish-in-net" approach. Encapsulated cells could perform normal metabolism and exhibited excellent reusability. The results presented here illustrate the enormous potential of the "fish-in-net" approach for immobilization of living cells. PMID- 24236146 TI - Subjective visual vertical and postural performance in healthy children. AB - INTRODUCTION: Verticality is essential in our life, especially for postural stability. Subjective vertical as well as postural stability depends on different sensorial information: visual, vestibular and somesthesic. They help to build the spatial referentials and create a central representation of verticality. Children are more visuo-dependant than adults; however, we did not find any study focusing on how children develop their sense of verticality. METHODS: WE STUDIED TWO GROUPS OF SUBJECTS: 10 children (from 6 to 8 years) and 12 young adults. We recorded postural stability with a Techno Concept plateform and perception of subjective visual vertical in the following conditions: while adjusting the vertical in the dark or with visual perturbation, while fixating the vertical bar, and with eyes closed. RESULTS: Children are more instable than adults in terms of postural parameters, and also while performing a double task, especially when no visual references are present. They also present a higher variability and lower accuracy than adults in reporting their perception of true vertical reference. DISCUSSION: Children might have limited attentional resources, and focus their attention on the more demanding task, corresponding to the U-shaped non-linear model. PMID- 24236147 TI - Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. AB - BACKGROUND: Postoperative cognitive dysfunction (POCD) is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12).The standardized mean difference (SMD) and the 95% confidence interval (95%CI) were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100beta(SMD[95%CI]) (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies), and interleukin(IL)-6 (SMD[95%CI]) (1.614 [0.603,2.624], p value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies), but not of neuron specific enolase, interleukin-1beta, or tumor necrosis factor-alpha , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p value=0.038, 5 studies). CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100beta. PMID- 24236148 TI - A simple alkaline method for decellularizing human amniotic membrane for cell culture. AB - Human amniotic membrane is a standard substratum used to culture limbal epithelial stem cells for transplantation to patients with limbal stem cell deficiency. Various methods were developed to decellularize amniotic membrane, because denuded membrane is poorly immunogenic and better supports repopulation by dissociated limbal epithelial cells. Amniotic membrane denuding usually involves treatment with EDTA and/or proteolytic enzymes; in many cases additional mechanical scraping is required. Although ensuring limbal cell proliferation, these methods are not standardized, require relatively long treatment times and can result in membrane damage. We propose to use 0.5 M NaOH to reliably remove amniotic cells from the membrane. This method was used before to lyse cells for DNA isolation and radioactivity counting. Gently rubbing a cotton swab soaked in NaOH over the epithelial side of amniotic membrane leads to nearly complete and easy removal of adherent cells in less than a minute. The denuded membrane is subsequently washed in a neutral buffer. Cell removal was more thorough and uniform than with EDTA, or EDTA plus mechanical scraping with an electric toothbrush, or n-heptanol plus EDTA treatment. NaOH-denuded amniotic membrane did not show any perforations compared with mechanical or thermolysin denuding, and showed excellent preservation of immunoreactivity for major basement membrane components including laminin alpha2, gamma1-gamma3 chains, alpha1/alpha2 and alpha6 type IV collagen chains, fibronectin, nidogen-2, and perlecan. Sodium hydroxide treatment was efficient with fresh or cryopreserved (10% dimethyl sulfoxide or 50% glycerol) amniotic membrane. The latter method is a common way of membrane storage for subsequent grafting in the European Union. NaOH-denuded amniotic membrane supported growth of human limbal epithelial cells, immortalized corneal epithelial cells, and induced pluripotent stem cells. This simple, fast and reliable method can be used to standardize decellularized amniotic membrane preparations for expansion of limbal stem cells in vitro before transplantation to patients. PMID- 24236149 TI - Analysis of morphological parameters to differentiate rupture status in anterior communicating artery aneurysms. AB - In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer(c) to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery aneurysms. PMID- 24236151 TI - Joint attention without gaze following: human infants and their parents coordinate visual attention to objects through eye-hand coordination. AB - The coordination of visual attention among social partners is central to many components of human behavior and human development. Previous research has focused on one pathway to the coordination of looking behavior by social partners, gaze following. The extant evidence shows that even very young infants follow the direction of another's gaze but they do so only in highly constrained spatial contexts because gaze direction is not a spatially precise cue as to the visual target and not easily used in spatially complex social interactions. Our findings, derived from the moment-to-moment tracking of eye gaze of one-year-olds and their parents as they actively played with toys, provide evidence for an alternative pathway, through the coordination of hands and eyes in goal-directed action. In goal-directed actions, the hands and eyes of the actor are tightly coordinated both temporally and spatially, and thus, in contexts including manual engagement with objects, hand movements and eye movements provide redundant information about where the eyes are looking. Our findings show that one-year olds rarely look to the parent's face and eyes in these contexts but rather infants and parents coordinate looking behavior without gaze following by attending to objects held by the self or the social partner. This pathway, through eye-hand coupling, leads to coordinated joint switches in visual attention and to an overall high rate of looking at the same object at the same time, and may be the dominant pathway through which physically active toddlers align their looking behavior with a social partner. PMID- 24236152 TI - Double deception: ant-mimicking spiders elude both visually- and chemically oriented predators. AB - Biological mimicry is often multimodal, in that a mimic reinforces its resemblance to another organism via different kinds of signals that can be perceived by a specific target audience. In this paper we describe a novel scenario, in which a mimic deceives at least two distinct audiences, each of which relies primarily on a different sensory modality for decision-making. We have previously shown that Peckhamia picata, a myrmecomorphic spider that morphologically and behaviorally resembles the ant Camponotus nearcticus, experiences reduced predation by visually-oriented jumping spiders. Here we report that Peckhamia also faces reduced aggression from spider-hunting sphecid wasps as well as from its model ant, both of which use chemical cues to identify prey. We also report that Peckhamia does not chemically resemble its model ants, and that its total cuticular hydrocarbons are significantly lower than those of the ants and non-mimic spiders. Although further studies are needed to clarify the basis of Peckhamia's chemically-mediated protection, to our knowledge, such 'double deception,' in which a single organism sends misleading visual cues to one set of predators while chemically misleading another set, has not been reported; however, it is likely to be common among what have until now been considered purely visual mimics. PMID- 24236150 TI - Transforming growth factor beta inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation. AB - In adult tissue, vascular smooth muscle cells (VSMCs) exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor beta (TGFbeta) and the pro-proliferative cytokine platelet derived growth factor (PDGF). In this study, we investigated the interplay between TGFbeta and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFbeta completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFbeta. TGFbeta had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFbeta on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFbeta. siRNA against Smad4 completely reversed the inhibitory effect of TGFbeta on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFbeta-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFbeta via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle. PMID- 24236153 TI - Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile. AB - Clostridium difficile is an important pathogen of humans and animals, representing a significant global healthcare problem. The last decade has seen the emergence of epidemic BI/NAP1/027 and ribotype 078 isolates, associated with the onset of more severe disease and higher rates of morbidity and mortality. However, little is known about these isolates at the molecular level, partly due to difficulties in the genetic manipulation of these strains. Here we report the development of an optimised Tn916-mediated plasmid transfer system, and the use of this system to construct and complement spo0A mutants in a number of different C. difficile strain backgrounds. Spo0A is a global regulator known to control sporulation, but may also be involved in the regulation of potential virulence factors and other phenotypes. Recent studies have failed to elucidate the role of Spo0A in toxin A and toxin B production by C. difficile, with conflicting data published to date. In this study, we aimed to clarify the role of Spo0A in production of the major toxins by C. difficile. Through the construction and complementation of spo0A mutants in two ribotype 027 isolates, we demonstrate that Spo0A acts as a negative regulator of toxin A and toxin B production in this strain background. In addition, spo0A was disrupted and subsequently complemented in strain 630Deltaerm and, for the first time, in a ribotype 078 isolate, JGS6133. In contrast to the ribotype 027 strains, Spo0A does not appear to regulate toxin production in strain 630Deltaerm. In strain JGS6133, Spo0A appears to negatively regulate toxin production during early stationary phase, but has little effect on toxin expression during late stationary phase. These data suggest that Spo0A may differentially regulate toxin production in phylogenetically distinct C. difficile strain types. In addition, Spo0A may be involved in regulating some aspects of C. difficile motility. PMID- 24236154 TI - Description of the protocols for randomized controlled trials on cancer drugs conducted in Spain (1999-2003). AB - OBJECTIVE: To describe the characteristics of randomized controlled clinical trials (RCT) on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. METHODS: We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS) (Spanish Agency for Medicines and Medical Devices) during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. RESULTS: We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%), overall survival (20.7%), and progression-free survival (14.5%). Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724). Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001) and were more likely to implement centralized randomization (p<0.001), blinding of the intervention (p<0.001), and survival as primary outcome (p<0.001). Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01). In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7%) was lower. CONCLUSION: RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide on-going initiatives that aim to increase the transparency and quality of future research. PMID- 24236155 TI - Speaker sex influences processing of grammatical gender. AB - Spoken words carry linguistic and indexical information to listeners. Abstractionist models of spoken word recognition suggest that indexical information is stripped away in a process called normalization to allow processing of the linguistic message to proceed. In contrast, exemplar models of the lexicon suggest that indexical information is retained in memory, and influences the process of spoken word recognition. In the present study native Spanish listeners heard Spanish words that varied in grammatical gender (masculine, ending in -o, or feminine, ending in -a) produced by either a male or a female speaker. When asked to indicate the grammatical gender of the words, listeners were faster and more accurate when the sex of the speaker "matched" the grammatical gender than when the sex of the speaker and the grammatical gender "mismatched." No such interference was observed when listeners heard the same stimuli, but identified whether the speaker was male or female. This finding suggests that indexical information, in this case the sex of the speaker, influences not just processes associated with word recognition, but also higher level processes associated with grammatical processing. This result also raises questions regarding the widespread assumption about the cognitive independence and automatic nature of grammatical processes. PMID- 24236156 TI - Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease--role of sclerostin? AB - High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/beta-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption. PMID- 24236157 TI - The BtaF trimeric autotransporter of Brucella suis is involved in attachment to various surfaces, resistance to serum and virulence. AB - The adhesion of bacterial pathogens to host cells is an event that determines infection, and ultimately invasion and intracellular multiplication. Several evidences have recently shown that this rule is also truth for the intracellular pathogen Brucella. Brucella suis displays the unipolar BmaC and BtaE adhesins, which belong to the monomeric and trimeric autotransporter (TA) families, respectively. It was previously shown that these adhesins are involved in bacterial adhesion to host cells and components of the extracellular matrix (ECM). In this work we describe the role of a new member of the TA family of B. suis (named BtaF) in the adhesive properties of the bacterial surface. BtaF conferred the bacteria that carried it a promiscuous adhesiveness to various ECM components and the ability to attach to an abiotic surface. Furthermore, BtaF was found to participate in bacterial adhesion to epithelial cells and was required for full virulence in mice. Similar to BmaC and BtaE, the BtaF adhesin was expressed in a small subpopulation of bacteria, and in all cases, it was detected at the new pole generated after cell division. Interestingly, BtaF was also implicated in the resistance of B. suis to porcine serum. Our findings emphasize the impact of TAs in the Brucella lifecycle. PMID- 24236159 TI - Lifelong obesity in a polygenic mouse model prevents age- and diet-induced glucose intolerance- obesity is no road to late-onset diabetes in mice. AB - AIMS/HYPOTHESIS: Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance. METHODS: We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age- and high fat diet-dependent glucose tolerance. RESULTS: Phenotype selection over 146 generations increased body weight by about 2.7-fold in male 12-week DU6 mice (P<0.0001) if compared to unselected controls (Fzt:DU). Absolute epididymal fat mass was particularly responsive to weight selection and increased by more than 5 fold (P<0.0001) in male DU6 mice. At an age of 6 weeks DU6 mice consumed about twice as much food if compared to unselected controls (P<0.001). Absolute food consumption was higher at all time points measured in DU6 mice than in Fzt:DU mice. Between 6 and 12 weeks of age, absolute food intake was reduced by 15% in DU6 mice (P<0.001) but not in Fzt:DU mice. In both mouse lines feeding of the high fat diet elevated body mass if compared to the control diet (P<0.05). In contrast to controls, DU6 mice did not display high fat diet-induced increases of epididymal and renal fat. Control mice progressively developed glucose intolerance with advancing age and even more in response to the high fat diet. In contrast, obese DU6 mice did neither develop a glucose intolerant phenotype with progressive age nor when challenged with a high fat diet. CONCLUSIONS/INTERPRETATION: Our results from a polygenic mouse model demonstrate that genetically pre-determined and life-long obesity is no precondition of glucose intolerance later in life. PMID- 24236158 TI - The anti-tumor effects and molecular mechanisms of suberoylanilide hydroxamic acid (SAHA) on the aggressive phenotypes of ovarian carcinoma cells. AB - Histone deacetylase inhibitors (HDACi), such as suberoylanilide hydroxamic acid (SAHA), have been shown to act selectively on gene expression, and are potent inducers of growth arrest, differentiation and apoptosis in various types of cancers in vitro and in vivo. This study aimed to elucidate the anti-tumor effects and molecular mechanisms of SAHA on the aggressive phenotypes of ovarian carcinoma. Two pairs of cell lines (SKOV3 and SKOV3/DDP; HO8910 and HO8910-PM) were exposed to SAHA treatment, and the effects on acetyl-Histone H3 and H4 expression levels were analyzed and compared against the aggressive behaviors of ovarian carcinoma. Our results showed that SAHA suppressed proliferation in both a concentration- and time-dependent manner in all four cell lines; induced S/G2 arrest in SKOV3 and SKOV3/DDP cells; and conversely, induced G1 arrest in HO8910 and HO8910-PM cells. SAHA treatment induced apoptosis and reduced migration, invasion and lamellipodia formation in the ovarian carcinoma cells; furthermore, SAHA decreased expression of Cyclin B1 and CDC2P34 mRNA, and downregulated CDC2P34, Erk1/2, CyclinB1 and MMP-9 proteins. In contrast, SAHA increased expression of Caspase-3, p21 and p53 mRNA, and upregulated acetyl-Histones H3 and H4, Caspase-8, and p53 proteins. Basal acetylation of histone H3 and H4 was higher in ovarian carcinoma compared to normal ovarian tissues and benign ovarian tumors, and in borderline tumor than in normal ovarian tissues, and was positively correlated with differentiation and expression of the proliferative marker, Ki-67 (P < 0.05). We suggest that SAHA may suppress growth, migration and invasion in ovarian carcinoma cells, including cisplatin-resistant or highly invasive ovarian cells, by promoting histone acetylation and modulating their phenotype-related molecules. As such, aberrant acetylation of histone H3 and H4 may play an important role in the carcinogenesis and differentiation of ovarian carcinoma. PMID- 24236160 TI - Association of diabetes in pregnancy with child weight at birth, age 12 months and 5 years--a population-based electronic cohort study. AB - BACKGROUND: This study examines the effect of diabetes in pregnancy on offspring weight at birth and ages 1 and 5 years. METHODS: A population-based electronic cohort study using routinely collected linked healthcare data. Electronic medical records provided maternal diabetes status and offspring weight at birth and ages 1 and 5 years (n = 147,773 mother child pairs). Logistic regression models were used to obtain odds ratios to describe the association between maternal diabetes status and offspring size, adjusted for maternal pre-pregnancy weight, age and smoking status. FINDINGS: We identified 1,250 (0.9%) pregnancies with existing diabetes (27.8% with type 1 diabetes), 1,358 with gestational diabetes (0.9%) and 635 (0.4%) who developed diabetes post-pregnancy. Children whose mothers had existing diabetes were less likely to be large at 12 months (OR: 0.7 (95%CI: 0.6, 0.8)) than those without diabetes. Maternal diabetes was associated with high weight at age 5 years in children whose mothers had a high pre-pregnancy weight tertile (gestational diabetes, (OR:2.1 (95%CI:1.25-3.6)), existing diabetes (OR:1.3 (95%CI:1.0 to 1.6)). CONCLUSION: The prevention of childhood obesity should focus on mothers with diabetes with a high maternal pre-pregnancy weight. We found little evidence that diabetes in pregnancy leads to long term obesity 'programming'. PMID- 24236162 TI - Application of the UK foresight obesity model in Ireland: the health and economic consequences of projected obesity trends in Ireland. AB - BACKGROUND: Given the scale of the current obesity epidemic and associated health consequences there has been increasing concern about the economic burden placed on society in terms of direct healthcare costs and indirect societal costs. In the Republic of Ireland these costs were estimated at ?1.13 billion for 2009. The total direct healthcare costs for six major obesity related conditions (coronary heart disease & stroke, cancer, hypertension, type 2 diabetes and knee osteoarthritis) in the same year were estimated at ?2.55 billion. The aim of this research is to project disease burden and direct healthcare costs for these conditions in Ireland to 2030 using the established model developed by the Health Forum (UK) for the Foresight: Tackling Obesities project. METHODOLOGY: Routine data sources were used to derive incidence, prevalence, mortality and survival for six conditions as inputs for the model. The model utilises a two stage modelling process to predict future BMI rates, disease prevalence and costs. Stage 1 employs a non-linear multivariate regression model to project BMI trends; stage 2 employs a microsimulation approach to produce longitudinal projections and test the impact of interventions upon future incidence of obesity-related disease. RESULTS: Overweight and obesity are projected to reach levels of 89% and 85% in males and females respectively by 2030. This will result in an increase in the obesity related prevalence of CHD & stroke by 97%, cancers by 61% and type 2 diabetes by 21%. The direct healthcare costs associated with these increases will amount to ?5.4 billion by 2030. A 5% reduction in population BMI levels by 2030 is projected to result in ?495 million less being spent in obesity-related direct healthcare costs over twenty years. DISCUSSION: These findings have significant implications for policy, highlighting the need for effective strategies to prevent this avoidable health and economic burden. PMID- 24236161 TI - Impaired antibody response to influenza vaccine in HIV-infected and uninfected aging women is associated with immune activation and inflammation. AB - BACKGROUND: Aging and HIV infection are independently associated with excessive immune activation and impaired immune responses to vaccines, but their relationships have not been examined. METHODS: For selecting an aging population we enrolled 28 post-menopausal women including 12 healthy volunteers and 16 HIV infected women on antiretroviral treatment with <100 HIV RNA copies/ml. Antibody titers to trivalent influenza vaccination given during the 2011-2012 season were determined before and 4 weeks after vaccination. RESULTS: Seroprotective influenza antibody titers (>= 1:40) were observed in 31% HIV(+) and 58% HIV uninfected women pre-vaccination. Following vaccination, magnitude of antibody responses and frequency of seroprotection were lower in HIV(+) (75%) than in HIV( ) (91%) women. Plasma IL-21, the signature cytokine of T follicular helper cells (Tfh), and CD4 T cell IL-21R were upregulated with seroconversion (>= 4 fold increase in antibody titer). Post-vaccine antibody responses were inversely correlated with pre-vaccination plasma TNFalpha levels and with activated CD4 T cells, including activated peripheral (p)Tfh. Plasma TNFalpha levels were correlated with activated pTfh cells (r=0.48, p=0.02), and inversely with the post-vaccination levels of plasma IL-21 (r=-0.53, p=0.02). In vitro TNFalpha blockade improved the ability of CD4 T cells to produce IL-21 and of B cells to secrete immunoglobulins, and addition of exogenous IL-21 to cell cultures enhanced B cell function. Higher frequencies of activated and exhausted CD8 T and B cells were noted in HIV(+) women, but these markers did not show a correlation with antibody responses. CONCLUSIONS: In aging HIV-infected and uninfected women, activated CD4 and pTfh cells may compromise influenza vaccine-induced antibody response, for which a mechanism of TNFalpha-mediated impairment of pTfh-induced IL-21 secretion is postulated. Interventions aimed at reducing chronic inflammation and immune activation in aging, HIV-infected patients may improve their response to vaccines. PMID- 24236163 TI - Quantifying cancer absolute risk and cancer mortality in the presence of competing events after a myotonic dystrophy diagnosis. AB - Recent studies show that patients with myotonic dystrophy (DM) have an increased risk of specific malignancies, but estimates of absolute cancer risk accounting for competing events are lacking. Using the Swedish Patient Registry, we identified 1,081 patients with an inpatient and/or outpatient diagnosis of DM between 1987 and 2007. Date and cause of death and date of cancer diagnosis were extracted from the Swedish Cause of Death and Cancer Registries. We calculated non-parametric estimates of absolute cancer risk and cancer mortality accounting for the high non-cancer competing mortality associated with DM. Absolute cancer risk after DM diagnosis was 1.6% (95% CI=0.4-4%), 5% (95% CI=3-9%) and 9% (95% CI=6-13%) at ages 40, 50 and 60 years, respectively. Females had a higher absolute risk of all cancers combined than males: 9% (95% CI=4-14), and 13% (95% CI=9-20) vs. 2% (95%CI= 0.7-6) and 4% (95%CI=2-8) by ages 50 and 60 years, respectively) and developed cancer at younger ages (median age =51 years, range=22-74 vs. 57, range=43-84, respectively, p=0.02). Cancer deaths accounted for 10% of all deaths, with an absolute cancer mortality risk of 2% (95%CI=1 4.5%), 4% (95%CI=2-6%), and 6% (95%CI=4-9%) by ages 50, 60, and 70 years, respectively. No gender difference in cancer-specific mortality was observed (p=0.6). In conclusion, cancer significantly contributes to morbidity and mortality in DM patients, even after accounting for high competing DM mortality from non-neoplastic causes. It is important to apply population-appropriate, validated cancer screening strategies in DM patients. PMID- 24236164 TI - A conserved pre-block interaction motif regulates potassium channel activation and N-type inactivation. AB - N-type inactivation occurs when the N-terminus of a potassium channel binds into the open pore of the channel. This study examined the relationship between activation and steady state inactivation for mutations affecting the N-type inactivation properties of the Aplysia potassium channel AKv1 expressed in Xenopus oocytes. The results show that the traditional single-step model for N type inactivation fails to properly account for the observed relationship between steady state channel activation and inactivation curves. We find that the midpoint of the steady state inactivation curve depends in part on a secondary interaction between the channel core and a region of the N-terminus just proximal to the pore blocking peptide that we call the Inactivation Proximal (IP) region. The IP interaction with the channel core produces a negative shift in the activation and inactivation curves, without blocking the pore. A tripeptide motif in the IP region was identified in a large number of different N-type inactivation domains most likely reflecting convergent evolution in addition to direct descent. Point mutating a conserved hydrophobic residue in this motif eliminates the gating voltage shift, accelerates recovery from inactivation and decreases the amount of pore block produced during inactivation. The IP interaction we have identified likely stabilizes the open state and positions the pore blocking region of the N-terminus at the internal opening to the transmembrane pore by forming a Pre-Block (P state) interaction with residues lining the side window vestibule of the channel. PMID- 24236165 TI - Ordinal-level phylogenomics of the arthropod class Diplopoda (millipedes) based on an analysis of 221 nuclear protein-coding loci generated using next-generation sequence analyses. AB - BACKGROUND: The ancient and diverse, yet understudied arthropod class Diplopoda, the millipedes, has a muddled taxonomic history. Despite having a cosmopolitan distribution and a number of unique and interesting characteristics, the group has received relatively little attention; interest in millipede systematics is low compared to taxa of comparable diversity. The existing classification of the group comprises 16 orders. Past attempts to reconstruct millipede phylogenies have suffered from a paucity of characters and included too few taxa to confidently resolve relationships and make formal nomenclatural changes. Herein, we reconstruct an ordinal-level phylogeny for the class Diplopoda using the largest character set ever assembled for the group. METHODS: Transcriptomic sequences were obtained from exemplar taxa representing much of the diversity of millipede orders using second-generation (i.e., next-generation or high throughput) sequencing. These data were subject to rigorous orthology selection and phylogenetic dataset optimization and then used to reconstruct phylogenies employing Bayesian inference and maximum likelihood optimality criteria. Ancestral reconstructions of sperm transfer appendage development (gonopods), presence of lateral defense secretion pores (ozopores), and presence of spinnerets were considered. The timings of major millipede lineage divergence points were estimated. RESULTS: The resulting phylogeny differed from the existing classifications in a number of fundamental ways. Our phylogeny includes a grouping that has never been described (Juliformia+Merocheta+Stemmiulida), and the ancestral reconstructions suggest caution with respect to using spinnerets as a unifying characteristic for the Nematophora. Our results are shown to have significantly stronger support than previous hypotheses given our data. Our efforts represent the first step toward obtaining a well-supported and robust phylogeny of the Diplopoda that can be used to answer many questions concerning the evolution of this ancient and diverse animal group. PMID- 24236166 TI - Production of the first effective hyperimmune equine serum antivenom against Africanized bees. AB - Victims of massive bee attacks become extremely ill, presenting symptoms ranging from dizziness and headache to acute renal failure and multiple organ failure that can lead to death. Previous attempts to develop specific antivenom to treat these victims have been unsuccessful. We herein report a F(ab)(')(2)-based antivenom raised in horse as a potential new treatment for victims of multiple bee stings. The final product contains high specific IgG titers and is effective in neutralizing toxic effects, such as hemolysis, cytotoxicity and myotoxicity. The assessment of neutralization was revised and hemolysis, the primary toxic effect of these stings, was fully neutralized in vivo for the first time. PMID- 24236167 TI - Magnesium sulfate protects against the bioenergetic consequences of chronic glutamate receptor stimulation. AB - Extracellular glutamate is elevated following brain ischemia or trauma and contributes to neuronal injury. We tested the hypothesis that magnesium sulfate (MgSO4, 3 mM) protects against metabolic failure caused by excitotoxic glutamate exposure. Rat cortical neuron preparations treated in medium already containing a physiological concentration of Mg(2+) (1 mM) could be segregated based on their response to glutamate (100 uM). Type I preparations responded with a decrease or small transient increase in oxygen consumption rate (OCR). Type II neurons responded with >50% stimulation in OCR, indicating a robust response to increased energy demand without immediate toxicity. Pre-treatment with MgSO4 improved the initial bioenergetic response to glutamate and ameliorated subsequent loss of spare respiratory capacity, measured following addition of the uncoupler FCCP, in Type I but not Type II neurons. Spare respiratory capacity in Type I neurons was also improved by incubation with MgSO4 or NMDA receptor antagonist MK801 in the absence of glutamate treatment. This finding indicates that the major difference between Type I and Type II preparations is the amount of endogenous glutamate receptor activity. Incubation of Type II neurons with 5 uM glutamate prior to excitotoxic (100 uM) glutamate exposure recapitulated a Type I phenotype. MgSO4 protected against an excitotoxic glutamate-induced drop in neuronal ATP both with and without prior 5 uM glutamate exposure. Results indicate that MgSO4 protects against chronic moderate glutamate receptor stimulation and preserves cellular ATP following treatment with excitotoxic glutamate. PMID- 24236168 TI - Daily sitting time and all-cause mortality: a meta-analysis. AB - OBJECTIVE: To quantify the association between daily total sitting and all-cause mortality risk and to examine dose-response relationships with and without adjustment for moderate-to-vigorous physical activity. METHODS: Studies published from 1989 to January 2013 were identified via searches of multiple databases, reference lists of systematic reviews on sitting and health, and from authors' personal literature databases. We included prospective cohort studies that had total daily sitting time as a quantitative exposure variable, all-cause mortality as the outcome and reported estimates of relative risk, or odds ratios or hazard ratios with 95% confidence intervals. Two authors independently extracted the data and summary estimates of associations were computed using random effects models. RESULTS: Six studies were included, involving data from 595,086 adults and 29,162 deaths over 3,565,569 person-years of follow-up. Study participants were mainly female, middle-aged or older adults from high-income countries; mean study quality score was 12/15 points. Associations between daily total sitting time and all-cause mortality were not linear. With physical activity adjustment, the spline model of best fit had dose-response HRs of 1.00 (95% CI: 0.98-1.03), 1.02 (95% CI: 0.99-1.05) and 1.05 (95% CI: 1.02-1.08) for every 1-hour increase in sitting time in intervals between 0-3, >3-7 and >7 h/day total sitting, respectively. This model estimated a 34% higher mortality risk for adults sitting 10 h/day, after taking physical activity into account. The overall weighted population attributable fraction for all-cause mortality for total daily sitting time was 5.9%, after adjusting for physical activity. CONCLUSIONS: Higher amounts of daily total sitting time are associated with greater risk of all-cause mortality and moderate-to-vigorous physical activity appears to attenuate the hazardous association. These findings provide a starting point for identifying a threshold on which to base clinical and public health recommendations for overall sitting time, in addition to physical activity guidelines. PMID- 24236169 TI - The development of the mental representations of the magnitude of fractions. AB - We investigated the development of the mental representation of the magnitude of fractions during the initial stages of fraction learning in grade 5, 6 and 7 children as well as in adults. We examined the activation of global fraction magnitude in a numerical comparison task and a matching task. There were global distance effects in the comparison task, but not in the matching task. This suggests that the activation of the global magnitude representation of fractions is not automatic in all tasks involving magnitude judgments. The slope of the global distance effect increased during early fraction learning and declined by adulthood, demonstrating that the development of the fraction global distance effect differs from that of the integer distance effect. PMID- 24236170 TI - Linkage to HIV, TB and non-communicable disease care from a mobile testing unit in Cape Town, South Africa. AB - BACKGROUND: HIV counseling and testing may serve as an entry point for non communicable disease screening. OBJECTIVES: To determine the yield of newly diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. METHODS: A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. RESULTS: Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. CONCLUSION: Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID- 24236172 TI - Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease. AB - Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF). CF-related bone disease (CFBD) is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR), the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/-) mouse model. In the murine calvarial organ culture assay, Cftr /- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+) littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-kappaB ligand (Rankl) mRNA was detected, significantly less osteoprotegerin (Opg) was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH stimulated canonical Wnt signaling was defective in Cftr-/- murine calvarial osteoblasts. These results support that genetic inactivation of CFTR in osteoblasts contributes to low bone mass and that targeting osteoblasts may represent an effective strategy to treat CFBD. PMID- 24236171 TI - The first modern human dispersals across Africa. AB - The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0's sister clade, L1'6. We propose that the last common ancestor of modern human mtDNAs (carried by "mitochondrial Eve") possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African "megadroughts" of MIS 5 (marine isotope stage 5, 135-75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution. PMID- 24236173 TI - Five year nationwide incidence of rhegmatogenous retinal detachment requiring surgery in Korea. AB - PURPOSE: To define the incidence and demographic characteristics of rhegmatogenous retinal detachment (RRD) requiring surgery in Korea. DESIGN: Nationwide population-based retrospective study. METHODS: Patients who underwent surgery for RRD from 2007 to 2011 were retrospectively identified using the diagnostic code for RRD and the surgical codes for retinal detachment surgeries in the national claim database. The average incidence rate of RRD during the 5 year period was estimated using the population data of the 2010 Census in Korea. RESULTS: A total of 24,928 surgically treated RRD cases were identified. The average incidence of surgery requiring RRD was 10.39 cases per 100,000 person years [95% confidence interval (CI), 10.26-10.52). The incidence in men (11.32 cases per 100,000 person-years; 95% CI: 11.13-11.51) was significantly higher than that in women (9.47 cases per 100,000 person-years; 95% CI: 9.29-9.64) (p<0.001). The incidence of surgery requiring RRD showed a bimodal distribution across age groups, with one peak (28.55 cases per 100,000 person-years; 95% CI: 27.46-29.67) representing patients between 65 and 69 years of age and the second peak (approximately 8.5 per 100,000 person-years) representing patients between 20 and 29 years of age. The male-to-female ratio was approximately 1.0 for the peak-incidence age groups, whereas the ratio was higher for the other age groups. CONCLUSIONS: The incidence of RRD in the Korean population was similar to that reported previously, with the peak incidence being lower than that in the Caucasian population. The age-specific RRD incidence pattern in Korea followed a bimodal distribution. PMID- 24236174 TI - Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. AB - Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10) or MCT (sustained 60%VO2max, n=10) for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10). CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100 W under 12%O2 for 30 minutes) were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO2 at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-gamma at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-gamma ratio and decreased peroxide production during HE. PMID- 24236175 TI - Characterization of the vaginal microbiota among sexual risk behavior groups of women with bacterial vaginosis. AB - BACKGROUND: The pathogenesis of bacterial vaginosis (BV) remains elusive. BV may be more common among women who have sex with women (WSW). The objective of this study was to use 454 pyrosequencing to investigate the vaginal microbiome of WSW, women who have sex with women and men (WSWM), and women who have sex with men (WSM) with BV to determine if there are differences in organism composition between groups that may inform new hypotheses regarding the pathogenesis of BV. METHODS: Vaginal swab specimens from eligible women with BV at the Mississippi State Department of Health STD Clinic were used. After DNA extraction, 454 pyrosequencing of PCR-amplified 16S rRNA gene sequences was performed. Sequence data was classified using the Ribosomal Database Program classifer. Complete linkage clustering analysis was performed to compare bacterial community composition among samples. Differences in operational taxonomic units with an abundance of >= 2% between risk behavior groups were determined. Alpha and beta diversity were measured using Shannon's Index implemented in QIIME and Unifrac analysis, respectively. RESULTS: 33 WSW, 35 WSWM, and 44 WSM were included. The vaginal bacterial communities of all women clustered into four taxonomic groups with the dominant taxonomic group in each being Lactobacillus, Lachnospiraceae, Prevotella, and Sneathia. Regarding differences in organism composition between risk behavior groups, the abundance of Atopobium (relative ratio (RR)=0.24; 95%CI 0.11-0.54) and Parvimonas (RR=0.33; 95%CI 0.11-0.93) were significantly lower in WSW than WSM, the abundance of Prevotella was significantly higher in WSW than WSWM (RR=1.77; 95%CI 1.10-2.86), and the abundance of Atopobium (RR=0.41; 95%CI 0.18-0.88) was significantly lower in WSWM than WSM. Overall, WSM had the highest diversity of bacterial taxa. CONCLUSION: The microbiology of BV among women in different risk behavior groups is heterogeneous. WSM in this study had the highest diversity of bacterial taxa. Additional studies are needed to better understand these differences. PMID- 24236176 TI - Purpose in life predicts better emotional recovery from negative stimuli. AB - Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life's experiences, especially when confronting life's challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation. PMID- 24236177 TI - A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease. AB - Alzheimer's disease is a progressive neurodegenerative disease that manifests as memory loss, cognitive dysfunction, and dementia. Animal models of Alzheimer's disease have been instrumental in understanding the underlying pathological mechanism and in evaluation of potential therapies. The triple transgenic (3 * Tg) mouse model of AD is unique because it recapitulates both pathologic hallmarks of Alzheimer's disease--amyloid plaques and neurofibrillary tangles. The earliest cognitive deficits in this model have been shown at 6-m of age by most groups, necessitating aging of the mice to this age before initiating evaluation of the cognitive effects of therapies. To assess cognitive deficits in the 3 * Tg mice, originally we employed a typical Barnes maze protocol of 15 training trials, but found no significant deficits in aged mice. Therefore, we shortened the protocol to include only 5 training trials to increase difficulty. We found cognitive deficits using this protocol using mainly measures from the probe day, rather than the training trials. This also decreased the effort involved with data analysis. We compared 3 * Tg and wild-type mice at 4-m- and 15 m of age using both the original, long training, and the short training paradigms. We found that differences in learning between 3 * Tg and wild-type mice disappeared after the 4(th) training trial. Measures of learning and memory on the probe day showed significant differences between 3 * Tg and wild-type mice following the short, 5-training trial protocol but not the long, 15-training trial protocol. Importantly, we detected cognitive dysfunction already at 4-m of age in 3 * Tg mice using the short Barnes-maze protocol. The ability to test learning and memory in 4-m old 3 * Tg mice using a shortened Barnes maze protocol offers considerable time and cost savings and provides support for the utilization of this model at pre-pathology stages for therapeutic studies. PMID- 24236178 TI - Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain. AB - Adherens junctions (AJs) play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and alpha-catenin and recruits the cadherin-beta-catenin complex to the nectin based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO) of the afadin gene. Newborn afadin cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain. PMID- 24236179 TI - Endothelial nitric oxide synthase regulates white matter changes via the BDNF/TrkB pathway after stroke in mice. AB - Stroke induced white matter (WM) damage is associated with neurological functional deficits, but the underlying mechanisms are not well understood. In this study, we investigate whether endothelial nitric oxide synthase (eNOS) affects WM-damage post-stroke. Adult male wild-type (WT) and eNOS knockout (eNOS( /-)) mice were subjected to middle cerebral artery occlusion. Functional evaluation, infarct volume measurement, immunostaining and primary cortical cell culture were performed. To obtain insight into the mechanisms underlying the effects of eNOS(-/-) on WM-damage, measurement of eNOS, brain-derived neurotrophic factor (BDNF) and its receptor TrkB in vivo and in vitro were also performed. No significant differences were detected in the infarction volume, myelin density in the ipsilateral striatal WM-bundles and myelin-based protein expression in the cerebral ischemic border between WT and eNOS(-/-) mice. However, eNOS(-/-) mice showed significantly: 1) decreased functional outcome, concurrent with decreases of total axon density and phosphorylated high-molecular weight neurofilament density in the ipsilateral striatal WM-bundles. Correlation analysis showed that axon density is significantly positive correlated with neurological functional outcome; 2) decreased numbers of oligodendrocytes / oligodendrocyte progenitor cells in the ipsilateral striatum; 3) decreased synaptophysin, BDNF and TrkB expression in the ischemic border compared with WT mice after stroke (n = 12/group, p<0.05). Primary cortical cell culture confirmed that the decrease of neuronal neurite outgrowth in the neurons derived from eNOS( /-) mice is mediated by the reduction of BDNF/TrkB (n = 6/group, p<0.05). Our data show that eNOS plays a critical role in WM-damage after stroke, and eNOS(-/ )-induced decreases in the BDNF/TrkB pathway may contribute to increased WM damage, and thereby decrease functional outcome. PMID- 24236180 TI - Characterization of Enterococcus faecalis phage IME-EF1 and its endolysin. AB - Enterococcus faecalis is increasingly becoming an important nosocomial infection opportunistic pathogen. E. faecalis can easily obtain drug resistance, making it difficult to be controlled in clinical settings. Using bacteriophage as an alternative treatment to drug-resistant bacteria has been revitalized recently, especially for fighting drug-resistant bacteria. In this research, an E. faecalis bacteriophage named IME-EF1 was isolated from hospital sewage. Whole genomic sequence analysis demonstrated that the isolated IME-EF1 belong to the Siphoviridae family, and has a linear double-stranded DNA genome consisting of 57,081 nucleotides. The IME-EF1 genome has a 40.04% G+C content and contains 98 putative coding sequences. In addition, IME-EF1 has an isometric head with a width of 35 nm to 60 nm and length of 75 nm to 90 nm, as well as morphology resembling a tadpole. IME-EF1 can adsorb to its host cells within 9 min, with an absorbance rate more than 99% and a latent period time of 25 min. The endolysin of IME-EF1 contains a CHAP domain in its N-terminal and has a wider bactericidal spectrum than its parental bacteriophage, including 2 strains of vancomycin resistant E. faecalis. When administrated intraperitoneally, one dose of IME-EF1 or its endolysin can reduce bacterial count in the blood and protected the mice from a lethal challenge of E. faecalis, with a survival rate of 60% or 80%, respectively. Although bacteriophage could rescue mice from bacterial challenge, to the best of our knowledge, this study further supports the potential function of bacteriophage in dealing with E. faecalis infection in vivo. The results also indicated that the newly isolated bacteriophage IME-EF1 enriched the arsenal library of lytic E. faecalis bacteriophages and presented another choice for phage therapy in the future. PMID- 24236181 TI - Role of exercise in the management of diabetes mellitus: the global scenario. AB - BACKGROUND: Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians. METHODS: Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results. RESULTS: Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM. CONCLUSION: Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM. PMID- 24236182 TI - Runx3-mediated transcriptional program in cytotoxic lymphocytes. AB - The transcription factor Runx3 is highly expressed in CD8(+) T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still missing. Using Runx3-ChIP-seq and transcriptome analysis of wild type vs. Runx3(-/-) primary cells we have now identified Runx3-regulated genes in the two cell types at both resting and IL-2-activated states. Runx3-bound genomic regions in both cell types were distantly located relative to gene transcription start sites and were enriched for RUNX and ETS motifs. Bound genomic regions significantly overlapped T-bet and p300-bound enhancer regions in Runx3 expressing Th1 helper cells. Compared to resting cells, IL-2-activated CD8(+) T and NK cells contain three times more Runx3-regulated genes that are common to both cell types. Functional annotation of shared CD8(+) T and NK Runx3-regulated genes revealed enrichment for immune-associated terms including lymphocyte activation, proliferation, cytotoxicity, migration and cytokine production, highlighting the role of Runx3 in CD8(+) T and NK activated cells. PMID- 24236184 TI - Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel. AB - Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy. PMID- 24236183 TI - High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. AB - INTRODUCTION: Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. OBJECTIVE: To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high fat diets using a model with conventional rats for 2, 4 and 6 weeks. MATERIAL AND METHODS: Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. RESULTS AND DISCUSSION: Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID- 24236185 TI - Exploring risk perception and attitudes to miscarriage and congenital anomaly in rural Western Kenya. AB - BACKGROUND: Understanding the socio-cultural context and perceptions of adverse pregnancy outcomes is important for informing the best approaches for public health programs. This article describes the perceptions, beliefs and health seeking behaviours of women from rural western Kenya regarding congenital anomalies and miscarriages. METHODS: Ten focus group discussions (FGDs) were undertaken in a rural district in western Kenya in September 2010. The FGDs included separate groups consisting of adult women of childbearing age, adolescent girls, recently pregnant women, traditional birth attendants and mothers of children with a birth defect. Participants were selected purposively. A deductive thematic framework approach using the questions from the FGD guides was used to analyse the transcripts. RESULTS: There was substantial overlap between perceived causes of miscarriages and congenital anomalies and these were broadly categorized into two groups: biomedical and cultural. The biomedical causes included medications, illnesses, physical and emotional stresses, as well as hereditary causes. Cultural beliefs mostly related to the breaking of a taboo or not following cultural norms. Mothers were often stigmatised and blamed following miscarriage, or the birth of a child with a congenital anomaly. Often, women did not seek care following miscarriage unless there was a complication. Most reported that children with a congenital anomaly were neglected either because of lack of knowledge of where care could be sought or because these children brought shame to the family and were hidden from society. CONCLUSION: The local explanatory model of miscarriage and congenital anomalies covered many perceived causes within biomedical and cultural beliefs. Some of these fuelled stigmatisation and blame of the mother. Understanding of these beliefs, improving access to information about the possible causes of adverse outcomes, and greater collaboration between traditional healers and healthcare providers may help to reduce stigma and increase access to formal healthcare providers. PMID- 24236186 TI - Genetic variation of human papillomavirus type 16 in individual clinical specimens revealed by deep sequencing. AB - Viral genetic diversity within infected cells or tissues, called viral quasispecies, has been mostly studied for RNA viruses, but has also been described among DNA viruses, including human papillomavirus type 16 (HPV16) present in cervical precancerous lesions. However, the extent of HPV genetic variation in cervical specimens, and its involvement in HPV-induced carcinogenesis, remains unclear. Here, we employ deep sequencing to comprehensively analyze genetic variation in the HPV16 genome isolated from individual clinical specimens. Through overlapping full-circle PCR, approximately 8-kb DNA fragments covering the whole HPV16 genome were amplified from HPV16 positive cervical exfoliated cells collected from patients with either low-grade squamous intraepithelial lesion (LSIL) or invasive cervical cancer (ICC). Deep sequencing of the amplified HPV16 DNA enabled de novo assembly of the full-length HPV16 genome sequence for each of 7 specimens (5 LSIL and 2 ICC samples). Subsequent alignment of read sequences to the assembled HPV16 sequence revealed that 2 LSILs and 1 ICC contained nucleotide variations within E6, E1 and the non coding region between E5 and L2 with mutation frequencies of 0.60% to 5.42%. In transient replication assays, a novel E1 mutant found in ICC, E1 Q381E, showed reduced ability to support HPV16 origin-dependent replication. In addition, partially deleted E2 genes were detected in 1 LSIL sample in a mixed state with the intact E2 gene. Thus, the methods used in this study provide a fundamental framework for investigating the influence of HPV somatic genetic variation on cervical carcinogenesis. PMID- 24236187 TI - Increased numbers of circulating CD8 effector memory T cells before transplantation enhance the risk of acute rejection in lung transplant recipients. AB - The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naive T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8(+) effector memory T cells over 185 cells/mm(3) had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8(+) effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection. PMID- 24236188 TI - Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence. AB - Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis. PMID- 24236189 TI - TGFbetas modulate permeability of the blood-epididymis barrier in an in vitro model. AB - The blood-epididymis barrier (BEB) is formed by epithelial tight junctions mediating selective permeability of the epididymal epithelium. Defective barrier function can disturb the balance of the epididymal milieu, which may result in infertility. The stroma of the epididymis contains high amounts of cytokines of the TGFbeta family of unknown function. We screened possible effects of all three TGFbeta isoforms on paracellular tightness in a BEB in vitro model based on the strongly polarized mouse epididymal epithelial MEPC5 cells in the transwell system. In this model we found a robust transepithelial electrical resistance (TER) of about 840 Omega x cm(2). Effects on the paracellular permeability were evaluated by two methods, TER and FITC-Dextran-based tracer diffusion assays. Both assays add up to corresponding results indicating a time-dependent disturbance of the BEB differentially for the three TGFbeta isoforms (TGFbeta3>TGFbeta1>TGFbeta2) in a TGFbeta-receptor-1 kinase- and Smad-dependent manner. The tight junction protein claudin-1 was found to be reduced by the treatment with TGFbetas, whereas occludin was not influenced. Epididymal epithelial cells are predominantly responsive to TGFbetas from the basolateral side, suggesting that TGFbeta may have an impact on the epididymal epithelium from the stroma in vivo. Our data show for the first time that TGFbetas decrease paracellular tightness in epididymal epithelial cells, thus establishing a novel mechanism of regulation of BEB permeability, which is elementary for sperm maturation and male fertility. PMID- 24236190 TI - Impact of pregnancy-associated malaria on infant malaria infection in southern Benin. AB - BACKGROUND: Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life. METHODOLOGY/ PRINCIPAL FINDINGS: To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother's age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively. CONCLUSIONS/ SIGNIFICANCE: This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers. PMID- 24236191 TI - Reduced prevalence of malaria infection in children living in houses with window screening or closed eaves on Bioko Island, equatorial Guinea. AB - BACKGROUND: Previous studies demonstrated that fewer mosquitoes enter houses which are screened or have closed eaves. There is little evidence about the effect on malaria infection in humans that changes in house construction may have. This study examines the impact of protective housing improvements on malaria infection on Bioko Island. METHODOLOGY/PRINCIPAL FINDINGS: Data from the annual malaria indicator surveys between 2009 and 2012 were used to assess trends in housing characteristics and their effect on RDT confirmed malaria infection in household members. Odds ratios were adjusted for socio-economic status of the household.22726 children between the ages of 2 and 14 years were tested for P. falciparum. Prevalence of infection in those living in houses with open eaves was 23.0% compared to 18.8% for those living in houses with closed eaves (OR = 0.81, 95% CI 0.67 - 0.98). The prevalence of infection for children in screened houses was 9.1% versus 20.1% for those living in unscreened houses (OR = 0.44, 95% CI 0.27 - 0.71). The proportion of houses with closed eaves increased from 66.0% in 2009 to 74.3% in 2012 (test for trend p = 0.01). The proportion of screened houses remained unchanged over time at 1.3%. CONCLUSION/SIGNIFICANCE: As a malaria control intervention, house modification has the advantages that it is not affected by the growing threat of insecticide resistance; it protects all household members equally and at all times while indoors; and it offers protection against a number of vector borne diseases. The study provides evidence in support of efforts to regulate or encourage housing improvements which impede vector access into residences as part of an integrated vector control approach to complement existing measures which have been only partially successful in reducing malaria transmission in some parts of Bioko. PMID- 24236192 TI - Behaviour of a new composite mesh for the repair of full-thickness abdominal wall defects in a rabbit model. AB - INTRODUCTION: Composite biomaterials designed for the repair of abdominal wall defects are composed of a mesh component and a laminar barrier in contact with the visceral peritoneum. This study assesses the behaviour of a new composite mesh by comparing it with two latest-generation composites currently used in clinical practice. METHODS: Defects (7x5cm) created in the anterior abdominal wall of New Zealand White rabbits were repaired using a polypropylene mesh and the composites: Physiomesh(TM); Ventralight(TM) and a new composite mesh with a three-dimensional macroporous polyester structure and an oxidized collagen/chitosan barrier. Animals were sacrificed on days 14 and 90 postimplant. Specimens were processed to determine host tissue incorporation, gene/protein expression of neo-collagens (RT-PCR/immunofluorescence), macrophage response (RAM 11-immunolabelling) and biomechanical resistance. On postoperative days 7/14, each animal was examined laparoscopically to quantify adhesions between the visceral peritoneum and implant. RESULTS: The new composite mesh showed the lowest incidence of seroma in the short term. At each time point, the mesh surface covered with adhesions was greater in controls than composites. By day 14, the implants were fully infiltrated by a loose connective tissue that became denser over time. At 90 days, the peritoneal mesh surface was lined with a stable mesothelium. The new composite mesh induced more rapid tissue maturation than Physiomesh(TM), giving rise to a neoformed tissue containing more type I collagen. In Ventralight(TM) the macrophage reaction was intense and significantly greater than the other composites at both follow-up times. Tensile strengths were similar for each biomaterial. CONCLUSIONS: All composites showed optimal peritoneal behaviour, inducing good peritoneal regeneration and scarce postoperative adhesion formation. A greater foreign body reaction was observed for Ventralight(TM). All composites induced good collagen deposition accompanied by optimal tensile strength. The three-dimensional macroporous structure of the new composite mesh may promote rapid tissue regeneration within the mesh. PMID- 24236193 TI - Prognostic importance and therapeutic implications of PAK1, a drugable protein kinase, in gastroesophageal junction adenocarcinoma. AB - Gastroesophageal junction (GEJ) adenocarcinoma is a lethal cancer with rising incidence, yet the molecular biomarkers that have strong prognostic impact and also hold great therapeutic promise remain elusive. We used a data mining approach and identified the p21 protein-activated kinase 1 (PAK1), an oncogene and drugable protein kinase, to be among the most promising targets for GEJ adenocarcinoma. Immunoblot analysis and data mining demonstrated that PAK1 protein and mRNA were upregulated in cancer tissues compared to the noncancerous tissues. Immunohistochemistry revealed PAK1 overexpression in 72.6% of primary GEJ adenocarcinomas (n = 113). A step-wise increase in PAK1 levels was noted from paired normal epithelium, to atypical hyperplasia and adenocarcinoma. PAK1 overexpression in tumor was associated with lymph node (LN) metastasis (P<0.001), advanced tumor stage (P<0.001), large tumor size (P = 0.006), residual surgical margin (P = 0.033), and unfavorable overall survival (P<0.001). Multivariate analysis showed PAK1 overexpression is an independent high-risk prognostic predictor (P<0.001). Collectively, PAK1 is overexpressed during tumorigenic progression and its upregulation correlates with malignant properties mainly relevant to invasion and metastasis. PAK1 expression could serve as a prognostic predictor that holds therapeutic promise for GEJ adenocarcinoma. PMID- 24236194 TI - Prediction and characterization of small non-coding RNAs related to secondary metabolites in Saccharopolyspora erythraea. AB - Saccharopolyspora erythraea produces a large number of secondary metabolites with biological activities, including erythromycin. Elucidation of the mechanisms through which the production of these secondary metabolites is regulated may help to identify new strategies for improved biosynthesis of erythromycin. In this paper, we describe the systematic prediction and analysis of small non-coding RNAs (sRNAs) in S. erythraea, with the aim to elucidate sRNA-mediated regulation of secondary metabolite biosynthesis. In silico and deep-sequencing technologies were applied to predict sRNAs in S. erythraea. Six hundred and forty-seven potential sRNA loci were identified, of which 382 cis-encoded antisense RNA are complementary to protein-coding regions and 265 predicted transcripts are located in intergenic regions. Six candidate sRNAs (sernc292, sernc293, sernc350, sernc351, sernc361, and sernc389) belong to four gene clusters (tpc3, pke, pks6, and nrps5) that are involved in secondary metabolite biosynthesis. Deep sequencing data showed that the expression of all sRNAs in the strain HL3168 E3 (E3) was higher than that in NRRL23338 (M), except for sernc292 and sernc361 expression. The relative expression of six sRNAs in strain M and E3 were validated by qRT-PCR at three different time points (24, 48, and 72 h). The results showed that, at each time point, the transcription levels of sernc293, sernc350, sernc351, and sernc389 were higher in E3 than in M, with the largest difference observed at 72 h, whereas no signals for sernc292 and sernc361 were detected. sernc293, sernc350, sernc351, and sernc389 probably regulate iron transport, terpene metabolism, geosmin synthesis, and polyketide biosynthesis, respectively. The major significance of this study is the successful prediction and identification of sRNAs in genomic regions close to the secondary metabolism related genes in S. erythraea. A better understanding of the sRNA-target interaction would help to elucidate the complete range of functions of sRNAs in S. erythraea, including sRNA-mediated regulation of erythromycin biosynthesis. PMID- 24236197 TI - Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the Wnt/beta-catenin signaling pathway. AB - Osteoblastoma is a bone forming tumor with histological features highly similar to osteoid osteoma; the discrimination between the tumor types is based on size and growth pattern. The vast majority of osteoblastomas are benign but there is a group of so-called aggressive osteoblastomas that can be diagnostically challenging at the histopathological level. The genetic aberrations required for osteoblastoma development are not known and no genetic difference between conventional and aggressive osteoblastoma has been reported. In order to identify recurrent genomic aberrations of importance for tumor development we applied cytogenetic and/or SNP array analyses on nine conventional and two aggressive osteoblastomas. The conventional osteoblastomas showed few or no acquired genetic aberrations while the aggressive tumors displayed heavily rearranged genomes. In one of the aggressive osteoblastomas, three neighboring regions in chromosome band 22q12 were homozygously deleted. Hemizygous deletions of these regions were found in two additional cases, one aggressive and one conventional. In total, 10 genes were recurrently and homozygously lost in osteoblastoma. Four of them are functionally involved in regulating osteogenesis and/or tumorigenesis. MN1 and NF2 have previously been implicated in the development of leukemia and solid tumors, and ZNRF3 and KREMEN1 are inhibitors of the Wnt/beta-catenin signaling pathway. In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma. PMID- 24236195 TI - Glycated hemoglobin independently predicts stroke recurrence within one year after acute first-ever non-cardioembolic strokes onset in A Chinese cohort study. AB - OBJECTIVE: Hyperglycemia is related to stroke. Glycated hemoglobin (HbA1c) can reflect pre-stroke glycaemia status. However, the information on the direct association between HbA1c and recurrence after non-cardioembolic acute ischemic strokes is rare and there is no consistent conclusion. METHODS: The ACROSS-China database comprised of 2186 consecutive first-ever acute ischemic stroke patients with baseline HbA1c values. After excluding patients who died from non-stroke recurrence and patients lost to follow up, 1817 and 1540 were eligible for 3 month and 1-year analyses, respectively. Multivariate Cox regression was performed to evaluate the associations between HbA1c and 3-month and 1-year stroke recurrence. RESULTS: The HbA1c values at admission were divided into 4 levels by quartiles: Q1 (<5.5%); Q2 (5.5 to <6.1%); Q3 (6.1% to <7.2%); and Q4 (>= 7.2%). The cumulative recurrence rates were 8.3% and 11.0% for 3 months and 1 year, respectively. In multivariate analyses, when compared with Q1, the adjusted hazard ratios (AHRs) were 2.83 (95% confidence interval (CI) 1.28-6.26) in Q3 and 3.71(95% CI 1.68-8.21) in Q4 for 3-month stroke recurrence; 3.30 (95% CI 1.31 8.34) in Q3 and 3.35 (95% CI 1.36-8.21) in Q4 for 1-year stroke recurrence. Adding fasting plasma glucose in the multivariate analyses did not modify the association: AHRs were 2.75 (95% CI 1.24-6.11) in Q3 and 3.67 (95% CI 1.59-8.53) in Q4 for 3-month analysis; AHRs were 3.08 (95% CI 1.10-8.64) in Q3 and 3.31(95% CI 1.35-8.14) in Q4 for 1-year analysis. CONCLUSIONS: A higher "normal" HbA1c level reflecting pre-stroke glycaemia status independently predicts stroke recurrence within one year after non-cardioembolic acute ischemic stroke onset. HbA1c is recommended as a routine test in acute ischemic stroke patients. PMID- 24236196 TI - Differential regulation of disheveled in a novel vegetal cortical domain in sea urchin eggs and embryos: implications for the localized activation of canonical Wnt signaling. AB - Pattern formation along the animal-vegetal (AV) axis in sea urchin embryos is initiated when canonical Wnt (cWnt) signaling is activated in vegetal blastomeres. The mechanisms that restrict cWnt signaling to vegetal blastomeres are not well understood, but there is increasing evidence that the egg's vegetal cortex plays a critical role in this process by mediating localized "activation" of Disheveled (Dsh). To investigate how Dsh activity is regulated along the AV axis, sea urchin-specific Dsh antibodies were used to examine expression, subcellular localization, and post-translational modification of Dsh during development. Dsh is broadly expressed during early sea urchin development, but immunolocalization studies revealed that this protein is enriched in a punctate pattern in a novel vegetal cortical domain (VCD) in the egg. Vegetal blastomeres inherit this VCD during embryogenesis, and at the 60-cell stage Dsh puncta are seen in all cells that display nuclear beta-catenin. Analysis of Dsh post translational modification using two-dimensional Western blot analysis revealed that compared to Dsh pools in the bulk cytoplasm, this protein is differentially modified in the VCD and in the 16-cell stage micromeres that partially inherit this domain. Dsh localization to the VCD is not directly affected by disruption of microfilaments and microtubules, but unexpectedly, microfilament disruption led to degradation of all the Dsh pools in unfertilized eggs over a period of incubation suggesting that microfilament integrity is required for maintaining Dsh stability. These results demonstrate that a pool of differentially modified Dsh in the VCD is selectively inherited by the vegetal blastomeres that activate cWnt signaling in early embryos, and suggests that this domain functions as a scaffold for localized Dsh activation. Localized cWnt activation regulates AV axis patterning in many metazoan embryos. Hence, it is possible that the VCD is an evolutionarily conserved cytoarchitectural domain that specifies the AV axis in metazoan ova. PMID- 24236198 TI - Comparative xylose metabolism among the Ascomycetes C. albicans, S. stipitis and S. cerevisiae. AB - The ascomycetes Candida albicans, Saccharomyces cerevisiae and Scheffersomyces stipitis metabolize the pentose sugar xylose very differently. S. cerevisiae fails to grow on xylose, while C. albicans can grow, and S. stipitis can both grow and ferment xylose to ethanol. However, all three species contain highly similar genes that encode potential xylose reductases and xylitol dehydrogenases required to convert xylose to xylulose, and xylulose supports the growth of all three fungi. We have created C. albicans strains deleted for the xylose reductase gene GRE3, the xylitol dehydrogenase gene XYL2, as well as the gre3 xyl2 double mutant. As expected, all the mutant strains cannot grow on xylose, while the single gre3 mutant can grow on xylitol. The gre3 and xyl2 mutants are efficiently complemented by the XYL1 and XYL2 from S. stipitis. Intriguingly, the S. cerevisiae GRE3 gene can complement the Cagre3 mutant, while the ScSOR1 gene can complement the Caxyl2 mutant, showing that S. cerevisiae contains the enzymatic capacity for converting xylose to xylulose. In addition, the gre3 xyl2 double mutant of C. albicans is effectively rescued by the xylose isomerase (XI) gene of either Piromyces or Orpinomyces, suggesting that the XI provides an alternative to the missing oxido-reductase functions in the mutant required for the xylose xylulose conversion. Overall this work suggests that C. albicans strains engineered to lack essential steps for xylose metabolism can provide a platform for the analysis of xylose metabolism enzymes from a variety of species, and confirms that S. cerevisiae has the genetic potential to convert xylose to xylulose, although non-engineered strains cannot proliferate on xylose as the sole carbon source. PMID- 24236199 TI - Dopamine and pain sensitivity: neither sulpiride nor acute phenylalanine and tyrosine depletion have effects on thermal pain sensations in healthy volunteers. AB - Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain. PMID- 24236200 TI - The role of metabotropic glutamate receptor 5 on the stromal cell-derived factor 1/CXCR4 system in oral cancer. AB - We have demonstrated that blocking CXCR4 may be a potent anti-metastatic therapy for CXCR4-related oral cancer. However, as CXCR4 antagonists are currently in clinical use to induce the mobilization of hematopoietic stem cells, continuous administration as an inhibitor for the metastasis may lead to persistent leukocytosis. In this study, we investigated the novel therapeutic downstream target(s) of the SDF-1/CXCR4 system, using B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and exhibit distant metastatic potential in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. We identified a gene that is highly upregulated in B88-SDF-1 cells, metabotropic glutamate receptor 5 (mGluR5), which was downregulated following treatment with 1,1' -[1,4-Phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist. The upregulation of mGluR5 mRNA in the SDF-1/CXCR4 system was predominately regulated by the Ras-extracellular signal-regulated kinase (ERK)1/2 pathway. Additionally, the growth of B88-SDF-1 cells was not affected by the mGluR5 agonist (S)-3,5-DHPG (DHPG) or the mGluR5 antagonists 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3 thiazol-4-yl)ethynyl)pyridine (MTEP). However, we observed that DHPG promoted B88 SDF-1 cell migration, whereas both MPEP and MTEP inhibited B88-SDF-1 cell migration. To assess drug toxicity, the antagonists were intraperitoneally injected into immunocompetent mice for 4 weeks. Mice injected with MPEP (5 mg/kg) and MTEP (5 mg/kg) did not exhibit any side effects, such as hematotoxicity, allergic reactions or weight loss. The administration of antagonists significantly inhibited the metastasis of B88-SDF-1 cells to the lungs of nude mice. These results suggest that blocking mGluR5 with antagonists such as MPEP and MTEP could prevent metastasis in CXCR4-related oral cancer without causing side effects. PMID- 24236201 TI - Platelet P2Y12 is involved in murine pulmonary metastasis. AB - The involvement of platelets in tumor progression is well recognized. The depletion of circulating platelets or pharmacologic inhibitors of platelet activation decreases the metastatic potential of circulating tumor cells in metastasis mouse models. The platelet ADP receptor P2Y12 amplifies the initial hemostatic responses activated by a variety of platelet agonists and stabilizes platelet aggregation, playing a crucial role in granule secretion, integrin activation and thrombus formation. However, the relationship between P2Y12 and tumor progression is not clear. In our study, the Lewis Lung Carcinoma (LLC) spontaneous metastatic mouse model was used to evaluate the role of P2Y12 in metastasis. The results demonstrated that P2Y12 deficiency significantly reduced pulmonary metastasis. Further studies indicated that P2Y12 deficiency diminished the ability of LLC cells to induce platelet shape change and release of active TGFbeta1 by a non-contact dependent mechanism resulting in a diminished, platelet induced EMT-like transformation of the LLC cells, and that transformation probably is a prerequisite of LLC cell metastasis. Immunohistochemical analyses indicated an obvious P2Y12 deficiency related attenuation of recruitment of VEGFR1+ bone marrow derived cell clusters, and extracellular matrix fibronectin deposition in lungs, which presumably are required for pre-metastatic niche formation. In contrast to the LLC cells, non-epithelial melanoma B16 cells induced platelet aggregation in a cell number and P2Y12-dependent manner. Also, a platelet induced EMT-like transformation of B16 cells is dependent on P2Y12. In agreement with the LLC cell model, platelet P2Y12 deficiency also results in significantly less lung metastasis in the B16 melanoma experimental metastasis model. These results demonstrate that P2Y12 is a safe drug target for anti thrombotic therapy, and that P2Y12 may serve as a new target for inhibition of tumor metastasis. PMID- 24236202 TI - Ambient air pollution associated with suppressed serologic responses to Pneumocystis jirovecii in a prospective cohort of HIV-infected patients with Pneumocystis pneumonia. AB - BACKGROUND: Ambient air pollution (AAP) may be associated with increased risk for Pneumocystis pneumonia (PCP). The mechanisms underlying this association remain uncertain. OBJECTIVES: To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P. jirovecii in HIV-infected (HIV+) patients with active PCP, and to determine if AAP, mediated by suppressed serologic responses to Pneumocystis, is associated with adverse clinical outcomes. METHODS: We conducted a prospective cohort study in HIV+ patients residing in San Francisco and admitted to San Francisco General Hospital with microscopically confirmed PCP. Our AAP predictors were ambient air concentrations of particulate matter of < 10 um in diameter (PM10) and < 2.5 um in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2) measured immediately prior to hospital admission and 2 weeks prior to admission. Our primary outcomes were the IgM serologic responses to four recombinant P. jirovecii major surface glycoprotein (Msg) constructs: MsgC1, MsgC3, MsgC8, and MsgC9. RESULTS: Elevated PM10 and NO2 exposures immediately prior to and two weeks prior to hospital admission were associated with decreased IgM antibody responses to P. jirovecii Msg. For exposures immediately prior to admission, every 10 ug/m(3) increase in PM10 was associated with a 25 to 35% decrease in IgM responses to Msg (statistically significant for all the Msg constructs), and every 10 ppb increase in NO2 was associated with a 19-45% decrease in IgM responses to Msg (statistically significant for MsgC8 and MsgC9). Similar findings were seen with exposures two weeks prior to admission, but for fewer of the Msg constructs. CONCLUSIONS: Real life exposures to PM10 and NO2 were associated with suppressed IgM responses to P. jirovecii Msg in HIV+ patients admitted with PCP, suggesting a mechanism of immunotoxicity by which AAP increases host susceptibility to pulmonary infection. PMID- 24236203 TI - Clinical features and factors associated with severity and fatality among patients with severe fever with thrombocytopenia syndrome Bunyavirus infection in Northeast China. AB - BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV) was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6%) of 115 patients presented with multiple organ dysfunction, and 22 (19.1%) of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2%) were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin <= 30 g/l (OR, 8.09; 95% CI, 2.58-25.32), APTT >= 66 seconds (OR, 14.28; 95% CI, 3.28-62.24), sodium <= 130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40), and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12). Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48-14.19) and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38-13.03) were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians. PMID- 24236204 TI - AKIP1 expression modulates mitochondrial function in rat neonatal cardiomyocytes. AB - A kinase interacting protein 1 (AKIP1) is a molecular regulator of protein kinase A and nuclear factor kappa B signalling. Recent evidence suggests AKIP1 is increased in response to cardiac stress, modulates acute ischemic stress response, and is localized to mitochondria in cardiomyocytes. The mitochondrial function of AKIP1 is, however, still elusive. Here, we investigated the mitochondrial function of AKIP1 in a neonatal cardiomyocyte model of phenylephrine (PE)-induced hypertrophy. Using a seahorse flux analyzer we show that PE stimulated the mitochondrial oxygen consumption rate (OCR) in cardiomyocytes. This was partially dependent on PE mediated AKIP1 induction, since silencing of AKIP1 attenuated the increase in OCR. Interestingly, AKIP1 overexpression alone was sufficient to stimulate mitochondrial OCR and in particular ATP-linked OCR. This was also true when pyruvate was used as a substrate, indicating that it was independent of glycolytic flux. The increase in OCR was independent of mitochondrial biogenesis, changes in ETC density or altered mitochondrial membrane potential. In fact, the respiratory flux was elevated per amount of ETC, possibly through enhanced ETC coupling. Furthermore, overexpression of AKIP1 reduced and silencing of AKIP1 increased mitochondrial superoxide production, suggesting that AKIP1 modulates the efficiency of electron flux through the ETC. Together, this suggests that AKIP1 overexpression improves mitochondrial function to enhance respiration without excess superoxide generation, thereby implicating a role for AKIP1 in mitochondrial stress adaptation. Upregulation of AKIP1 during different forms of cardiac stress may therefore be an adaptive mechanism to protect the heart. PMID- 24236205 TI - The antiepileptic drug levetiracetam suppresses non-convulsive seizure activity and reduces ischemic brain damage in rats subjected to permanent middle cerebral artery occlusion. AB - The antiepileptic drug Levetiracetam (Lev) has neuroprotective properties in experimental stroke, cerebral hemorrhage and neurotrauma. In these conditions, non-convulsive seizures (NCSs) propagate from the core of the focal lesion into perilesional tissue, enlarging the damaged area and promoting epileptogenesis. Here, we explore whether Lev neuroprotective effect is accompanied by changes in NCS generation or propagation. In particular, we performed continuous EEG recordings before and after the permanent occlusion of the middle cerebral artery (pMCAO) in rats that received Lev (100 mg/kg) or its vehicle immediately before surgery. Both in Lev-treated and in control rats, EEG activity was suppressed after pMCAO. In control but not in Lev-treated rats, EEG activity reappeared approximately 30-45 min after pMCAO. It initially consisted in single spikes and, then, evolved into spike-and-wave and polyspike-and-wave discharges. In Lev treated rats, only rare spike events were observed and the EEG power was significantly smaller than in controls. Approximately 24 hours after pMCAO, EEG activity increased in Lev-treated rats because of the appearance of polyspike events whose power was, however, significantly smaller than in controls. In rats sacrificed 24 hours after pMCAO, the ischemic lesion was approximately 50% smaller in Lev-treated than in control rats. A similar neuroprotection was observed in rats sacrificed 72 hours after pMCAO. In conclusion, in rats subjected to pMCAO, a single Lev injection suppresses NCS occurrence for at least 24 hours. This electrophysiological effect could explain the long lasting reduction of ischemic brain damage caused by this drug. PMID- 24236206 TI - The caveolin-1 scaffolding domain peptide decreases phosphatidylglycerol levels and inhibits calcium-induced differentiation in mouse keratinocytes. AB - Phospholipase D2 (PLD2) has been found localized in low-density caveolin-rich membrane microdomains. Our previous study suggested that PLD2 and aquaporin 3 (AQP3) interact in these domains to inhibit keratinocyte proliferation and promote differentiation by cooperating to produce phosphatidylglycerol. To examine the effect of membrane microdomain localization on the PLD2/AQP3 signaling module and keratinocyte proliferation and differentiation, we treated mouse keratinocytes with 3 uM cell-permeable caveolin-1 scaffolding domain peptide or a negative control peptide and stimulated cell differentiation using a moderately elevated extracellular calcium concentration (125 uM) to maximally promote differentiation and phosphatidylglycerol production. Cell proliferation, differentiation, total PLD activity, phosphatidylglycerol levels, and AQP3 activity were monitored. The caveolin-1 scaffolding domain peptide itself had no effect on phosphatidylglycerol levels or keratinocyte proliferation or differentiation but prevented the changes induced by a moderately elevated calcium concentration, whereas a negative control did not. The caveolin-1 scaffolding domain peptide had little effect on total PLD activity or glycerol uptake (AQP3 activity). We conclude that the caveolin-1 scaffolding domain peptide disrupts the functional association between AQP3 and PLD2 and prevents both the inhibited proliferation and the stimulated differentiation in response to elevated extracellular calcium levels. The interaction of caveolin-1 and PLD2 is indirect (i.e., lipid mediated); together with the proliferation-promoting effects of caveolin-1 knockout on epidermal keratinocytes, we propose that the caveolin-1 scaffolding domain pepetide exerts a dominant-negative effect on caveolin-1 to alter lipid rafts in these cells. PMID- 24236207 TI - Adaptations in muscle activity to induced, short-term hindlimb lameness in trotting dogs. AB - Muscle tissue has a great intrinsic adaptability to changing functional demands. Triggering more gradual responses such as tissue growth, the immediate responses to altered loading conditions involve changes in the activity. Because the reduction in a limb's function is associated with marked deviations in the gait pattern, understanding the muscular responses in laming animals will provide further insight into their compensatory mechanisms as well as help to improve treatment options to prevent musculoskeletal sequelae in chronic patients. Therefore, this study evaluated the changes in muscle activity in adaptation to a moderate, short-term, weight-bearing hindlimb lameness in two leg and one back muscle using surface electromyography (SEMG). In eight sound adult dogs that trotted on an instrumented treadmill, bilateral, bipolar recordings of the m. triceps brachii, the m. vastus lateralis and the m. longissimus dorsi were obtained before and after lameness was induced. Consistent with the unchanged vertical forces as well as temporal parameters, neither the timing nor the level of activity changed significantly in the m. triceps brachii. In the ipsilateral m. vastus lateralis, peak activity and integrated SEMG area were decreased, while they were significantly increased in the contralateral hindlimb. In both sides, the duration of the muscle activity was significantly longer due to a delayed offset. These observations are in accordance with previously described kinetic and kinematic changes as well as changes in muscle mass. Adaptations in the activity of the m. longissimus dorsi concerned primarily the unilateral activity and are discussed regarding known alterations in trunk and limb motions. PMID- 24236208 TI - Trophoblast cell fusion and differentiation are mediated by both the protein kinase C and a pathways. AB - The syncytiotrophoblast of the human placenta is an epithelial barrier that interacts with maternal blood and is a key for the transfer of nutrients and other solutes to the developing fetus. The syncytiotrophoblast is a true syncytium and fusion of progenitor cytotrophoblasts is the cardinal event leading to the formation of this layer. BeWo cells are often used as a surrogate for cytotrophoblasts, since they can be induced to fuse, and then express certain differentiation markers associated with trophoblast syncytialization. Dysferlin, a syncytiotrophoblast membrane repair protein, is up-regulated in BeWo cells induced to fuse by treatment with forskolin; this fusion is thought to occur through cAMP/protein kinase A-dependent mechanisms. We hypothesized that dysferlin may also be up-regulated in response to fusion through other pathways. Here, we show that BeWo cells can also be induced to fuse by treatment with an activator of protein kinase C, and that this fusion is accompanied by increased expression of dysferlin. Moreover, a dramatic synergistic increase in dysferlin expression is observed when both the protein kinase A and protein kinase C pathways are activated in BeWo cells. This synergy in fusion is also accompanied by dramatic increases in mRNA for the placental fusion proteins syncytin 1, syncytin 2, as well as dysferlin. Dysferlin, however, was shown to be dispensable for stimulus-induced BeWo cell syncytialization, since dysferlin knockdown lines fused to the same extent as control cells. The classical trophoblast differentiation marker human chorionic gonadotropin was also monitored and changes in the expression closely parallel that of dysferlin in all of the experimental conditions employed. Thus different biochemical markers of trophoblast fusion behave in concert supporting the hypothesis that activation of both protein kinase C and A pathways lead to trophoblastic differentiation. PMID- 24236210 TI - Cadmium mimics estrogen-driven cell proliferation and prolactin secretion from anterior pituitary cells. AB - Cadmium (Cd) is a heavy metal of considerable occupational and environmental concern affecting wildlife and human health. Recent studies indicate that Cd, like other heavy metals, can mimic effects of 17beta-estradiol (E2) involving E2 receptor (ER) activation. Lactotrophs, the most abundant cell type in anterior pituitary gland, are the main target of E2, which stimulates cell proliferation and increases prolactin secretion through ERalpha. The aim of this work was to examine whether Cd at nanomolar concentrations can induce cell proliferation and prolactin release in anterior pituitary cells in culture and whether these effects are mediated through ERs. Here we show that 10 nM Cd was able to stimulate lactotroph proliferation in anterior pituitary cell cultures from female Wistar rats and also in GH3 lactosomatotroph cell line. Proliferation of somatotrophs and gonadotrophs were not affected by Cd exposure. Cd promoted cell cycle progression by increasing cyclins D1, D3 and c-fos expression. Cd enhanced prolactin synthesis and secretion. Cd E2-like effects were blocked by the pure ERs antagonist ICI 182,780 supporting that Cd acts through ERs. Further, both Cd and E2 augmented full-length ERalphaexpression and its 46 kDa-splicing variant. In addition, when co-incubated Cd was shown to interact with E2 by inducing ERalpha mRNA expression which indicates an additive effect between them. This study shows for the first time that Cd at nanomolar concentration displays xenoestrogenic activities by inducing cell growth and stimulating prolactin secretion from anterior pituitary cells in an ERs-dependent manner. Cd acting as a potent xenoestrogen can play a key role in the aetiology of different pathologies of the anterior pituitary and in estrogen-responsive tissues which represent considerable risk to human health. PMID- 24236209 TI - Machine-based morphologic analysis of glioblastoma using whole-slide pathology images uncovers clinically relevant molecular correlates. AB - Pathologic review of tumor morphology in histologic sections is the traditional method for cancer classification and grading, yet human review has limitations that can result in low reproducibility and inter-observer agreement. Computerized image analysis can partially overcome these shortcomings due to its capacity to quantitatively and reproducibly measure histologic structures on a large-scale. In this paper, we present an end-to-end image analysis and data integration pipeline for large-scale morphologic analysis of pathology images and demonstrate the ability to correlate phenotypic groups with molecular data and clinical outcomes. We demonstrate our method in the context of glioblastoma (GBM), with specific focus on the degree of the oligodendroglioma component. Over 200 million nuclei in digitized pathology slides from 117 GBMs in the Cancer Genome Atlas were quantitatively analyzed, followed by multiplatform correlation of nuclear features with molecular and clinical data. For each nucleus, a Nuclear Score (NS) was calculated based on the degree of oligodendroglioma appearance, using a regression model trained from the optimal feature set. Using the frequencies of neoplastic nuclei in low and high NS intervals, we were able to cluster patients into three well-separated disease groups that contained low, medium, or high Oligodendroglioma Component (OC). We showed that machine-based classification of GBMs with high oligodendroglioma component uncovered a set of tumors with strong associations with PDGFRA amplification, proneural transcriptional class, and expression of the oligodendrocyte signature genes MBP, HOXD1, PLP1, MOBP and PDGFRA. Quantitative morphologic features within the GBMs that correlated most strongly with oligodendrocyte gene expression were high nuclear circularity and low eccentricity. These findings highlight the potential of high throughput morphologic analysis to complement and inform human-based pathologic review. PMID- 24236211 TI - Increased cell surface free thiols identify effector CD8+ T cells undergoing T cell receptor stimulation. AB - Recognition of peptide Major Histocompatibility Complexes (MHC) by the T cell receptor causes rapid production of reactive oxygen intermediates (ROI) in naive CD8(+) T cells. Because ROI such as H2O2 are membrane permeable, mechanisms must exist to prevent overoxidation of surface proteins. In this study we used fluorescently labeled conjugates of maleimide to measure the level of cell surface free thiols (CSFT) during the development, activation and differentiation of CD8(+) T cells. We found that during development CSFT were higher on CD8 SP compared to CD4 SP or CD4CD8 DP T cells. After activation CSFT became elevated prior to division but once proliferation started levels continued to rise. During acute viral infection CSFT levels were elevated on antigen-specific effector cells compared to memory cells. Additionally, the CSFT level was always higher on antigen-specific CD8(+) T cells in lymphoid compared to nonlymphoid organs. During chronic viral infection, CSFT levels were elevated for extended periods on antigen-specific effector CD8(+) T cells. Finally, CSFT levels on effector CD8(+) T cells, regardless of infection, identified cells undergoing TCR stimulation. Taken together these data suggest that CD8(+) T cells upregulate CSFT following receptor ligation and ROI production during infection to prevent overoxidation of surface proteins. PMID- 24236212 TI - Abnormal error monitoring in math-anxious individuals: evidence from error related brain potentials. AB - This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math anxious (HMA) and seventeen low math-anxious (LMA) individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN) in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct related negativity component (CRN), the error positivity component (Pe), classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants' math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA) we found greater activation of the insula in errors on a numerical task as compared to errors in a non-numerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN. PMID- 24236214 TI - Age-related expression of the polymeric immunoglobulin receptor (pIgR) in the gastric mucosa of young pigs. AB - To date few studies have addressed the development and function of the porcine gastric mucosal immune system and this is a major limitation to understanding the immunopathogenesis of infections occurring in young pigs. The polymeric immunoglobulin receptor (pIgR) mediates the transport of secretory immunoglobulins until luminal surface of the gut mucosa and the aim of this study was to investigate the time course of pIgR expression and to determine its localization in three functionally different porcine gastric sites during the suckling period and after weaning. An additional goal was to investigate the time course expression of toll-like receptors (TLRs) in relation to pIgR expression. Gastric samples were collected from the cardiac-to-oxyntic transition (Cd), the oxyntic (Ox), and the pyloric (Py) regions in 84 pigs, slaughtered before weaning (14, 21 and 28 days of age; 23, 23 and 19 pigs, respectively) and 14 days post weaning (42 days of age, 23 pigs). PIgR was expressed in the mucosa of all the three gastric sites, and its transcript levels were modulated during suckling and after weaning, with regional differences. PIgR expression increased linearly during suckling (P=0.019) and also increased post-weaning (P=0.001) in Cd, it increased post-weaning in Py (P=0.049) and increased linearly during suckling in Ox (P=0.036). TLRs expression was also modulated during development: in Cd, TLR2 increased linearly during suckling (P=0.003); in Ox, TLR2 decreased after weaning (P=0.038) while TLR4 increased linearly during suckling(P=0.008). The expression of TLR2, 3 and 4 in Ox was positively correlated with pIgR expression (P<0.001). Importantly, both pIgR protein and mRNA were localized, by immunohistochemistry and in situ hybridization, respectively, in the gastric glands of the lamina propria. These results indicate that pIgR is actively synthesized in the gastric mucosa and suggest that pIgR could play a crucial role in gastric mucosal immune defense of growing pigs. PMID- 24236213 TI - The Drosophila gypsy insulator supports transvection in the presence of the vestigial enhancer. AB - Though operationally defined as cis-regulatory elements, enhancers can also communicate with promoters on a separate homolog in trans, a mechanism that has been suggested to account for the ability of certain alleles of the same gene to complement one another in a process otherwise known as transvection. This homolog pairing dependent process is facilitated in Drosophila by chromatin-associated pairing proteins, many of which remain unknown and their mechanism of action uncharacterized. Here we have tested the role of the gypsy chromatin insulator in facilitating pairing and communication between enhancers and promoters in trans using a transgenic eGFP reporter system engineered to allow for targeted deletions in the vestigial Boundary Enhancer (vgBE) and the hsp70 minimal promoter, along with one or two flanking gypsy elements. We found a modest 2.5-3x increase in eGFP reporter levels from homozygotes carrying an intact copy of the reporter on each homolog compared to unpaired hemizygotes, although this behavior was independent of gypsy. However, detectable levels of GFP protein along the DV wing boundary in trans-heterozygotes lacking a single enhancer and promoter was only observed in the presence of two flanking gypsy elements. Our results demonstrate that gypsy can stimulate enhancer-promoter communication in trans throughout the genome in a context-dependent manner, likely through modulation of local chromatin dynamics once pairing has been established by other elements and highlights chromatin structure as the master regulator of this phenomenon. PMID- 24236215 TI - Adaptation aftereffects in vocal emotion perception elicited by expressive faces and voices. AB - The perception of emotions is often suggested to be multimodal in nature, and bimodal as compared to unimodal (auditory or visual) presentation of emotional stimuli can lead to superior emotion recognition. In previous studies, contrastive aftereffects in emotion perception caused by perceptual adaptation have been shown for faces and for auditory affective vocalization, when adaptors were of the same modality. By contrast, crossmodal aftereffects in the perception of emotional vocalizations have not been demonstrated yet. In three experiments we investigated the influence of emotional voice as well as dynamic facial video adaptors on the perception of emotion-ambiguous voices morphed on an angry-to happy continuum. Contrastive aftereffects were found for unimodal (voice) adaptation conditions, in that test voices were perceived as happier after adaptation to angry voices, and vice versa. Bimodal (voice + dynamic face) adaptors tended to elicit larger contrastive aftereffects. Importantly, crossmodal (dynamic face) adaptors also elicited substantial aftereffects in male, but not in female participants. Our results (1) support the idea of contrastive processing of emotions (2), show for the first time crossmodal adaptation effects under certain conditions, consistent with the idea that emotion processing is multimodal in nature, and (3) suggest gender differences in the sensory integration of facial and vocal emotional stimuli. PMID- 24236216 TI - AglQ is a novel component of the Haloferax volcanii N-glycosylation pathway. AB - N-glycosylation is a post-translational modification performed by members of all three domains of life. Studies on the halophile Haloferax volcanii have offered insight into the archaeal version of this universal protein-processing event. In the present study, AglQ was identified as a novel component of the pathway responsible for the assembly and addition of a pentasaccharide to select Asn residues of Hfx. volcanii glycoproteins, such as the S-layer glycoprotein. In cells deleted of aglQ, both dolichol phosphate, the lipid carrier used in Hfx. volcanii N-glycosylation, and modified S-layer glycoprotein Asn residues only presented the first three pentasaccharide subunits, pointing to a role for AglQ in either preparing the third sugar for attachment of the fourth pentasaccharide subunit or processing the fourth sugar prior to its addition to the lipid-linked trisaccharide. To better define the precise role of AglQ, shown to be a soluble protein, bioinformatics tools were recruited to identify sequence or structural homologs of known function. Site-directed mutagenesis experiments guided by these predictions identified residues important for AglQ function. The results obtained point to AglQ acting as an isomerase in Hfx. volcanii N-glycosylation. PMID- 24236219 TI - Correction: Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation. AB - [This corrects the article on p. e66377 in vol. 8.]. PMID- 24236217 TI - Structural insights for activation of retinal guanylate cyclase by GCAP1. AB - Guanylyl cyclase activating protein 1 (GCAP1), a member of the neuronal calcium sensor (NCS) subclass of the calmodulin superfamily, confers Ca(2+)-sensitive activation of retinal guanylyl cyclase 1 (RetGC1) upon light activation of photoreceptor cells. Here we present NMR assignments and functional analysis to probe Ca(2+)-dependent structural changes in GCAP1 that control activation of RetGC. NMR assignments were obtained for both the Ca(2+)-saturated inhibitory state of GCAP1 versus a GCAP1 mutant (D144N/D148G, called EF4mut), which lacks Ca(2+) binding in EF-hand 4 and models the Ca(2+)-free/Mg(2+)-bound activator state of GCAP1. NMR chemical shifts of backbone resonances for Ca(2+)-saturated wild type GCAP1 are overall similar to those of EF4mut, suggesting a similar main chain structure for assigned residues in both the Ca(2+)-free activator and Ca(2+)-bound inhibitor states. This contrasts with large Ca(2+)-induced chemical shift differences and hence dramatic structural changes seen for other NCS proteins including recoverin and NCS-1. The largest chemical shift differences between GCAP1 and EF4mut are seen for residues in EF4 (S141, K142, V145, N146, G147, G149, E150, L153, E154, M157, E158, Q161, L166), but mutagenesis of EF4 residues (F140A, K142D, L153R, L166R) had little effect on RetGC1 activation. A few GCAP1 residues in EF-hand 1 (K23, T27, G32) also show large chemical shift differences, and two of the mutations (K23D and G32N) each decrease the activation of RetGC, consistent with a functional conformational change in EF1. GCAP1 residues at the domain interface (V77, A78, L82) have NMR resonances that are exchange broadened, suggesting these residues may be conformationally dynamic, consistent with previous studies showing these residues are in a region essential for activating RetGC1. PMID- 24236218 TI - Crossmodal integration of conspecific vocalizations in rhesus macaques. AB - Crossmodal integration of audio/visual information is vital for recognition, interpretation and appropriate reaction to social signals. Here we examined how rhesus macaques process bimodal species-specific vocalizations by eye tracking, using an unconstrained preferential looking paradigm. Six adult rhesus monkeys (3M, 3F) were presented two side-by-side videos of unknown male conspecifics emitting different vocalizations, accompanied by the audio signal corresponding to one of the videos. The percentage of time animals looked to each video was used to assess crossmodal integration ability and the percentages of time spent looking at each of the six a priori ROIs (eyes, mouth, and rest of each video) were used to characterize scanning patterns. Animals looked more to the congruent video, confirming reports that rhesus monkeys spontaneously integrate conspecific vocalizations. Scanning patterns showed that monkeys preferentially attended to the eyes and mouth of the stimuli, with subtle differences between males and females such that females showed a tendency to differentiate the eye and mouth regions more than males. These results were similar to studies in humans indicating that when asked to assess emotion-related aspects of visual speech, people preferentially attend to the eyes. Thus, the tendency for female monkeys to show a greater differentiation between the eye and mouth regions than males may indicate that female monkeys were slightly more sensitive to the socio emotional content of complex signals than male monkeys. The current results emphasize the importance of considering both the sex of the observer and individual variability in passive viewing behavior in nonhuman primate research. PMID- 24236220 TI - Shape-correlated Deformation Statistics for Respiratory Motion Prediction in 4D Lung. AB - 4D image-guided radiation therapy (IGRT) for free-breathing lungs is challenging due to the complicated respiratory dynamics. Effective modeling of respiratory motion is crucial to account for the motion affects on the dose to tumors. We propose a shape-correlated statistical model on dense image deformations for patient-specic respiratory motion estimation in 4D lung IGRT. Using the shape deformations of the high-contrast lungs as the surrogate, the statistical model trained from the planning CTs can be used to predict the image deformation during delivery verication time, with the assumption that the respiratory motion at both times are similar for the same patient. Dense image deformation fields obtained by diffeomorphic image registrations characterize the respiratory motion within one breathing cycle. A point-based particle optimization algorithm is used to obtain the shape models of lungs with group-wise surface correspondences. Canonical correlation analysis (CCA) is adopted in training to maximize the linear correlation between the shape variations of the lungs and the corresponding dense image deformations. Both intra- and inter-session CT studies are carried out on a small group of lung cancer patients and evaluated in terms of the tumor location accuracies. The results suggest potential applications using the proposed method. PMID- 24236221 TI - Characterization of Image Quality for 3D Scatter Corrected Breast CT Images. AB - The goal of this study was to characterize the image quality of our dedicated, quasi-monochromatic spectrum, cone beam breast imaging system under scatter corrected and non-scatter corrected conditions for a variety of breast compositions. CT projections were acquired of a breast phantom containing two concentric sets of acrylic spheres that varied in size (1-8mm) based on their polar position. The breast phantom was filled with 3 different concentrations of methanol and water, simulating a range of breast densities (0.79-1.0g/cc); acrylic yarn was sometimes included to simulate connective tissue of a breast. For each phantom condition, 2D scatter was measured for all projection angles. Scatter-corrected and uncorrected projections were then reconstructed with an iterative ordered subsets convex algorithm. Reconstructed image quality was characterized using SNR and contrast analysis, and followed by a human observer detection task for the spheres in the different concentric rings. Results show that scatter correction effectively reduces the cupping artifact and improves image contrast and SNR. Results from the observer study indicate that there was no statistical difference in the number or sizes of lesions observed in the scatter versus non-scatter corrected images for all densities. Nonetheless, applying scatter correction for differing breast conditions improves overall image quality. PMID- 24236222 TI - Co-registration of high resolution MRI scans with partial brain coverage in non human primates. AB - Dynamic structural and functional remodeling of the Central Nervous System occurs throughout the lifespan of the organism from the molecular to the systems level. MRI offers several advantages to observe this phenomenon: it is non-invasive and non-destructive, the contrast can be tuned to interrogate different tissue properties and imaging resolution can range from cortical columns to whole brain networks in the same session. To measure these changes reliably, functional maps generated over time with high resolution fMRI need to be registered accurately. This article presents a new method for the automatic registration of thin cortical MR volumes that are aligned with the functional maps. These acquisitions focus on the primary somato-sensory cortex, a region in the anterior parietal part of the brain, responsible for fine touch and proprioception. Currently, these slabs are acquired in approximately the same orientation from acquisition to acquisition and then registered by hand. Because they only cover a small portion of the cortex, their direct automatic registration is difficult. To address this issue, we propose a method relying on an intermediate image, acquired with a surface coil that covers a larger portion of the head to which the slabs can be registered. Because images acquired with surface coils suffer from severe intensity attenuation artifact, we also propose a method to register these. The results from data sets obtained with 3 squirrel monkeys show a registration accuracy of 30 micrometers.). PMID- 24236223 TI - A Pico Projector Source for Confocal Fluorescence and Ophthalmic Imaging. AB - A Pico digital light projector has been implemented as an integrated illumination source and spatial light modulator for confocal imaging. The target is illuminated with a series of rapidly projected lines or points to simulate scanning. Light returning from the target is imaged onto a 2D rolling shutter CMOS sensor. By controlling the spatio-temporal relationship between the rolling shutter and illumination pattern, light returning from the target is spatially filtered. Confocal retinal, fluorescence, and Fourier-domain optical coherence tomography implementations of this novel imaging technique are presented. PMID- 24236224 TI - Automatic classification of scar tissue in late gadolinium enhancement cardiac MRI for the assessment of left-atrial wall injury after radiofrequency ablation. AB - Radiofrequency ablation is a promising procedure for treating atrial fibrillation (AF) that relies on accurate lesion delivery in the left atrial (LA) wall for success. Late Gadolinium Enhancement MRI (LGE MRI) at three months post-ablation has proven effective for noninvasive assessment of the location and extent of scar formation, which are important factors for predicting patient outcome and planning of redo ablation procedures. We have developed an algorithm for automatic classification in LGE MRI of scar tissue in the LA wall and have evaluated accuracy and consistency compared to manual scar classifications by expert observers. Our approach clusters voxels based on normalized intensity and was chosen through a systematic comparison of the performance of multivariate clustering on many combinations of image texture. Algorithm performance was determined by overlap with ground truth, using multiple overlap measures, and the accuracy of the estimation of the total amount of scar in the LA. Ground truth was determined using the STAPLE algorithm, which produces a probabilistic estimate of the true scar classification from multiple expert manual segmentations. Evaluation of the ground truth data set was based on both inter- and intra-observer agreement, with variation among expert classifiers indicating the difficulty of scar classification for a given a dataset. Our proposed automatic scar classification algorithm performs well for both scar localization and estimation of scar volume: for ground truth datasets considered easy, variability from the ground truth was low; for those considered difficult, variability from ground truth was on par with the variability across experts. PMID- 24236225 TI - Non-Mydriatic Confocal Retinal Imaging Using a Digital Light Projector. AB - A digital light projector is implemented as an integrated illumination source and scanning element in a confocal non-mydriatic retinal camera, the DLP-Cam. To simulate scanning, a series of illumination lines are rapidly projected on the retina. The backscattered light is imaged onto a 2-dimensional rolling shutter CMOS sensor. By temporally and spatially overlapping the illumination lines with the rolling shutter, confocal imaging is achieved. This approach enables a low cost, flexible, and robust design with a small footprint. Qualitative image comparison with commercial non-mydriatic SLOs and fundus cameras shows comparable fine vessel visibility and contrast. PMID- 24236226 TI - Towards Visual-Search Model Observers for Mass Detection in Breast Tomosynthesis. AB - We are investigating human-observer models that perform clinically realistic detection and localization tasks as a means of making reliable assessments of digital breast tomosynthesis images. The channelized non-prewhitening (CNPW) observer uses the background known exactly task for localization and detection. Visual-search observer models attempt to replicate the search patterns of trained radiologists. The visual-search observer described in this paper utilizes a two phase approach, with an initial holistic search followed by directed analysis and decision making. Gradient template matching is used for the holistic search, and the CNPW observer is used for analysis and decision making. Spherical masses were embedded into anthropomorphic breast phantoms, and simulated projections were made using ray-tracing and a serial cascade model. A localization ROC study was performed on these images using the visual-search model observer and the CNPW observer. Observer performance from the two computer observers was compared to human observer performance. The visual-search observer was able to produce area under the LROC curve values similar to those from human observers; however, more research is needed to increase the robustness of the algorithm. PMID- 24236227 TI - Voxel-Wise Displacement as Independent Features in Classification of Multiple Sclerosis. AB - We present a method that utilizes registration displacement fields to perform accurate classification of magnetic resonance images (MRI) of the brain acquired from healthy individuals and patients diagnosed with multiple sclerosis (MS). Contrary to standard approaches, each voxel in the displacement field is treated as an independent feature that is classified individually. Results show that when used with a simple linear discriminant and majority voting, the approach is superior to using the displacement field with a single classifier, even when compared against more sophisticated classification methods such as adaptive boosting, random forests, and support vector machines. Leave-one-out cross validation was used to evaluate this method for classifying images by disease, MS subtype (Acc: 77%-88%), and age (Acc: 96%-100%). PMID- 24236228 TI - Automatic Segmentation of Right Ventricle on Ultrasound Images Using Sparse Matrix Transform and Level Set. AB - An automatic framework is proposed to segment right ventricle on ultrasound images. This method can automatically segment both epicardial and endocardial boundaries from a continuous echocardiography series by combining sparse matrix transform (SMT), a training model, and a localized region based level set. First, the sparse matrix transform extracts main motion regions of myocardium as eigenimages by analyzing statistical information of these images. Second, a training model of right ventricle is registered to the extracted eigenimages in order to automatically detect the main location of the right ventricle and the corresponding transform relationship between the training model and the SMT extracted results in the series. Third, the training model is then adjusted as an adapted initialization for the segmentation of each image in the series. Finally, based on the adapted initializations, a localized region based level set algorithm is applied to segment both epicardial and endocardial boundaries of the right ventricle from the whole series. Experimental results from real subject data validated the performance of the proposed framework in segmenting right ventricle from echocardiography. The mean Dice scores for both epicardial and endocardial boundaries are 89.1%+/-2.3% and 83.6+/-7.3%, respectively. The automatic segmentation method based on sparse matrix transform and level set can provide a useful tool for quantitative cardiac imaging. PMID- 24236229 TI - AUTOMATED ANATOMICAL LABELING OF THE CEREBRAL ARTERIES USING BELIEF PROPAGATION. AB - Labeling of cerebral vasculature is important for characterization of anatomical variation, quantification of brain morphology with respect to specific vessels, and inter-subject comparisons of vessel properties and abnormalities. We propose an automated method to label the anterior portion of cerebral arteries using a statistical inference method on the Bayesian network representation of the vessel tree. Our approach combines the likelihoods obtained from a random forest classifier trained using vessel centerline features with a belief propagation method integrating the connection probabilities of the cerebral artery network. We evaluate our method on 30 subjects using a leave-one-out validation, and show that it achieves an average correct vessel labeling rate of over 92%. PMID- 24236230 TI - Biodistribution Study of Nanoparticle Encapsulated Photodynamic Therapy Drugs Using Multispectral Imaging. AB - Photodynamictherapy (PDT) uses a drug called a photosensitizer that is excited by irradiation with a laser light of a particular wavelength, which generates reactive singlet oxygen that damages the tumor cells. The photosensitizer and light are inert; therefore, systemic toxicities are minimized in PDT. The synthesis of novel PDT drugs and the use of nanosized carriers for photosensitizers may improve the efficiency of the therapy and the delivery of the drug. In this study, we formulated two nanoparticles with and without a targeting ligand to encapsulate phthalocyanines 4 (Pc 4) molecule and compared their biodistributions. Metastatic human head and neck cancer cells (M4e) were transplanted into nude mice. After 2-3 weeks, the mice were injected with Pc 4, Pc 4 encapsulated into surface coated iron oxide (IO-Pc 4), and IO-Pc 4 conjugated with a fibronectin-mimetic peptide (FMP-IO-Pc 4) which binds specifically to integrin beta1. The mice were imaged using a multispectral camera. Using multispectral images, a library of spectral signatures was created and the signal per pixel of each tumor was calculated, in a grayscale representation of the unmixed signal of each drug. An enhanced biodistribution of nanoparticle encapsulated PDT drugs compared to non-formulated Pc 4 was observed. Furthermore, specific targeted nanoparticles encapsulated Pc 4 has a quicker delivery time and accumulation in tumor tissue than the non-targeted nanoparticles. The nanoparticle-encapsulated PDT drug can have a variety of potential applications in cancer imaging and treatment. PMID- 24236231 TI - Sleep and epilepsy. PMID- 24236232 TI - Postoperative venous thromboembolism prophylaxis by general surgeons in a developing country: a survey. AB - Venous thromboembolism (VTE) is the most common preventable cause of hospital death. Several audits in the west have demonstrated that appropriate thromboprophylaxis is not being offered to a large number of surgical patients. Similar audits are lacking in the Indian population, and a perception exists among Indian surgeons that Indian patients are not susceptible to VTE. Hence we undertook a survey to analyze the existing knowledge and practice of VTE prophylaxis amongst general surgeons in India. A questionnaire-based survey was conducted on 100 active general surgeons. We found that 97% of surgeons had encountered VTE in their practice, and 49% had encountered mortality from pulmonary embolism. 64% of surgeons do not routinely score patients preoperatively for their VTE risk, and only 33% reported the presence of an institute-based protocol for the same. There was a wide disparity in the prophylaxis methods used for each risk group, particularly in the moderate-risk group. These findings suggest the need for adoption of institute-based protocols for prophylaxis and the evolution of Indian guidelines for VTE prophylaxis. PMID- 24236233 TI - Smiling in pain: explorations of its social motives. AB - Studies of facial responses during experimental and clinical pain have revealed a surprising phenomenon, namely, that a considerable number of individuals respond with a smile. So far, it is not known why smiling occurs during pain. It is possible that the "smile of pain" is socially motivated (e.g., reinforcing social bonds while undergoing an unpleasant experience). The present studies were conducted in an attempt to address the role of social motives in smiling during pain. In two studies, we varied the quantitative (level of sociality) and qualitative (properties of the relationship between interactants) components of the situations in which participants received painful stimulation. Participants' faces were video-recorded and the occurrence of smiling was assessed. The occurrence of smiling differed depending on stimulus intensity and the properties of the relationship between interactants. Smiling occurred more often during the painful compared to nonpainful stimulation. Whereas the presence of a stranger (experimenter) reduced the smiling behavior, the presence of an intimate other increased it. Slight variations in the level of sociality, however, had no effect on the degree of smiling. Social motives possibly aimed at strengthening social bonds and thus ensuring social support appear to underlie smiling during pain. PMID- 24236234 TI - A Longitudinal Study of Changes in Thyroid Related Hormones among Pregnant Women Residing in an Iodine Deficient Urban Area. AB - Problem Statement. Thyroid gland in women undergoes functional changes during pregnancy. A few studies have described such changes in pregnant women residing in iodine deficient areas. Objective. To document these changes in pregnant women residing in Lahore, a low iodine intake urban area of Pakistan. Patients and Methods. In 254 pregnant women, data of FT4, FT3, and TSH during the first and subsequent trimesters were obtained and compared with those of 110 nonpregnant women. These hormones were determined in serum by radioimmunoassay (RIA) techniques using commercial kits. Results. Compared to nonpregnant women mean FT4 level was decreased, and FT3 and TSH increased significantly (P < 0.05) in pregnant women. A negative correlation of FT4 with TSH was observed in all three trimesters. Serum FT3 was positively correlated with TSH only during the third trimester. As a function of gestation time, FT4 levels progressively decreased, and FT3 and TSH levels increased significantly (one-way ANOVA F = 108.2, 17.3, and 44.8, resp.; all P < 0.05) exhibiting thyroid gland adaptations. Conclusion. Pregnancy is associated with significant alterations in thyroid function due to low iodine intake in women residing in study area. The compensated thyroid function poses a risk of thyroid failure in a number of pregnant women. PMID- 24236235 TI - The effect of varicocelectomy on sperm parameters in subfertile men with clinical varicoceles who have asthenozoospermia or teratozoospermia with normal sperm density. AB - Background. To compare preoperative and postoperative sperm parameters such as sperm count, motility, and morphology in patients with normal sperm concentration with teratozoospermia and asthenozoospermia. Materials and Methods. Hundred and six patients with varicocele associated with male infertility over a 5-year period were included into the study. Pre- and postvaricocelectomy seminal fluid parameters evaluation according to the World Health Organization (WHO) criteria was performed at 4-6-month intervals. Results. One hundred and six patients met the criteria. The mean age of patients was 24.53 +/- 8.13. The mean duration of infertility was 3.6 years (range: 1.5-6.3). Only the sperm motility of patients with normospermia showed a significant improvement postoperatively. Conclusions. No significant improvement in sperm morphology may be obtained in patients with clinical varicocele and preoperative normospermia. PMID- 24236236 TI - Activation of the NF kappa B Pathway Enhances AhR Expression in Intestinal Caco-2 Cells. AB - Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 beta enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF kappa B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 beta blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management. PMID- 24236238 TI - Emotional and cognitive empathy in first-year medical students. AB - Objectives. Doctors' empathy towards their patients is considered important for treatment outcome. However, during medical school there might be a decline in empathy called "hardening of the heart." This study evaluated the cognitive and emotional empathy in medical students and investigated the influence of a preference for a specialty and students attachment styles. Methods. 126 first year medical students were included and completed the Reading the Mind in the Eyes Test revised version (RME-R), the Balanced Emotional Empathy Scale (BEES), and the Experiences in Close Relationships-Revised Adult Attachment Questionnaire (ECR-R). Results. Students identified 22 +/- 4.30 of 36 photographs in the RME-R test correctly (norm: 26). The female students' mean BEES total score was 51.1 +/ 17.1 and the male students' 27.2 +/- 22.6; P < 0.0001. The female students' mean BEES score was significantly (P = 0.0037) below the female norm of 60. Students who preferred a specialty with continuity of patient care scored significantly higher in the BEES (P = 0.014). A more avoidant attachment style was associated with a lower BEES score (P = 0.021). Conclusion. The students showed low emotional and cognitive empathy scores and an avoidant attachment style. This supports the inclusion of specific training in cognitive and emotional empathy in medical education. PMID- 24236237 TI - Processing of damaged DNA ends for double-strand break repair in mammalian cells. AB - Most DNA double-strand breaks (DSBs)formed in a natural environment have chemical modifications at or near the ends that preclude direct religation and require removal or other processing so that rejoining can proceed. Free radical-mediated DSBs typically bear unligatable 3'-phosphate or 3'-phosphoglycolate termini and often have oxidized bases and/or abasic sites near the break. Topoisomerase mediated DSBs are blocked by covalently bound peptide fragments of the topoisomerase. Enzymes capable of resolving damaged ends include polynucleotide kinase/phosphatase, which restores missing 5'-phosphates and removes 3' phosphates; tyrosyl-DNA phosphodiesterases I and II (TDP1 and TDP2), which remove peptide fragments of topoisomerases I and II, respectively, and the Artemis and Metnase endonucleases, which can trim damaged overhangs of diverse structure. TDP1 as well as APE1 can remove 3'-phosphoglycolates and other 3' blocks, while CtIP appears to provide an alternative pathway for topoisomerase II fragment removal. Ku, a core DSB joining protein, can cleave abasic sites near DNA ends. The downstream processes of patching and ligation are tolerant of residual damage, and can sometimes proceed without complete damage removal. Despite these redundant pathways for resolution, damaged ends appear to be a significant barrier to rejoining, and their resolution may be a rate-limiting step in repair of some DSBs.. PMID- 24236239 TI - Blastomyces dermatitidis Yeast Lysate Antigen Combinations: Antibody Detection in Dogs with Blastomycosis. AB - The systemic fungal infection, blastomycosis, which infects both humans and animals has presented a diagnostic challenge for clinicians for many years. The aim of this study was to evaluate the diagnostic sensitivity of Blastomyces dermatitidis yeast lysate antigens with respect to antibody detection in dogs with blastomycosis. Lysate antigens were prepared from B. dermatitidis isolates T 58 and T-66 (dogs, Tennessee) and WI-R and WI-J (dogs, Wisconsin). Based on results obtained from a preliminary comparative study, five combinations of these isolates and one individual isolate were tested against 92 serum specimens from dogs with culture-proven or histologically-confirmed blastomycosis, using the indirect enzyme-linked immunosorbent assay (ELISA). Mean absorbance values obtained from the sera ranged from 0.905 with the individual T-58 antigen to 1.760 using an antigen combination (T-58 + T-66 + WI-R). All of the 6 antigenic preparations were able to detect antibody in the serum specimens, but the antigen combinations detected antibody to a higher degree than the individual antigen. This study provides evidence that combinations of the yeast lysate reagents seem to be more efficacious for antibody detection in dog sera, but our laboratory is continuing to evaluate antigen lysate combinations for detection of antibodies in blastomycosis. PMID- 24236240 TI - Curcumin attenuation of lipopolysaccharide induced cardiac hypertrophy in rodents. AB - To study the ameliorating effects of curcumin in lipopolysaccharide (LPS) induced cardiac hypertrophy, mice were assigned to 4 groups (3 males and 3 females in each group): (A) control, (B) curcumin: 100 MU g/kg of body weight by intraperitoneal route (IP), (C) LPS: 60 mg/kg (IP), and (D) LPS + curcumin: both at previously stated concentrations by IP route. All mice were sacrificed as 12 hr and 24 hrs groups accordingly after LPS injection. The hearts were collected, photographed for cardiomegaly, and weighed to compare heart weight/brain weight (HW/BW) in mg/mg. For immunohistochemistry, the tissue sections were exposed to histone H3, H4 and acetylated histone H3, H4 antibody. LPS induced a significant increase in histone acetylation as shown by intense staining. In curcumin + LPS treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the LPS. To further check the mechanism of action of curcumin, p300 protein acetylation levels were analyzed. This study suggests that the probable mechanism of action of curcumin is via the reduction of p300 HAT activity. PMID- 24236241 TI - Waiting for innovations in periodontal disease diagnosis. PMID- 24236243 TI - Determination of levels of nitric oxide in smoker and nonsmoker patients with chronic periodontitis. AB - PURPOSE: Cigarette smoking is a major risk factor in periodontal diseases. The pathogenesis of periodontal diseases may be affected by alterations of the inflammatory response by smoke. Nitric oxide (NO) is a gaseous, colorless, highly reactive, short-lived free radical with a pivotal role in the regulation of various physiological and pathological mechanisms in the body. It is important in host defense and homeostasis, on the one hand, whereas, on the other hand, it modulates the inflammatory response in periodontitis, leading to harmful effects. The aim of this study was to assess the levels of NO in both the serum and saliva of smokers and nonsmokers having chronic periodontitis and to compare them with periodontally healthy controls. METHODS: SIXTY SUBJECTS PARTICIPATED IN THE STUDY AND WERE DIVIDED INTO THREE GROUPS: group I, healthy nonsmoking subjects; group II, nonsmoking patients with chronic periodontitis; group III, smoking patients with chronic periodontitis. Each group consisted of twenty subjects. The biochemical estimation of NO in the collected serum and in the saliva was performed using the Griess colorimetric reaction. RESULTS: The results showed that the mean value of the salivary and serum NO was greater in group II than in group I, and also greater in group III than in group II. CONCLUSIONS: NO appears to play an important and rather complex role in the immuno-inflammatory process and in the remodeling and maintenance of osseous structures. It is therefore logical that modulation of this mediator has potential for the treatment of a number of inflammatory conditions including periodontal disease. PMID- 24236242 TI - Changes in the fractal dimension of peri-implant trabecular bone after loading: a retrospective study. AB - PURPOSE: To assess bony trabecular changes potentially caused by loading stress around dental implants using fractal dimension analysis. METHODS: Fractal dimensions were measured in 48 subjects by comparing radiographs taken immediately after prosthesis delivery with those taken 1 year after functional loading. Regions of interest were isolated, and fractal analysis was performed using the box-counting method with Image J 1.42 software. Wilcoxon signed-rank test was used to analyze the difference in fractal dimension before and after implant loading. RESULTS: The mean fractal dimension before loading (1.4213+/ 0.0525) increased significantly to 1.4329+/-0.0479 at 12 months after loading (P<0.05). CONCLUSIONS: Fractal dimension analysis might be helpful in detecting changes in peri-implant alveolar trabecular bone patterns in clinical situations. PMID- 24236244 TI - The combined effect of dismantling for steam sterilization and aging on the accuracy of spring-style mechanical torque devices. AB - PURPOSE: This study aimed to assess the combined effect of dismantling before sterilization and aging on the accuracy (+/-10% of the target torque) of spring style mechanical torque devices (S-S MTDs). METHODS: Twenty new S-SMTDs from two different manufacturers (Nobel Biocare and Straumann: 10 of each type) were selected and divided into two groups, namely, case (group A) and control (group B). For sterilization, 100 cycles of autoclaving were performed in 100 sequences. In each sequence, 10 repetitions of peak torque values were registered for aging. To measure and assess the output of each device, a Tohnichi torque gauge was used (P<0.05). RESULTS: Before steam sterilization, all of the tested devices stayed within 10% of their target values. After 100 cycles of steam sterilization and aging with or without dismantling of the devices, the Nobel Biocare devices stayed within 10% of their target torque. In the Straumann devices, despite the significant difference between the peak torque and target torque values, the absolute error values stayed within 10% of their target torque. CONCLUSION: Within the limitations of this study, there was no significant difference between the mean and absolute value of error between Nobel Biocare and Straumann S-S MTDs. PMID- 24236245 TI - Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health. AB - PURPOSE: The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system plays a significant role in osteoclastogenesis, activation of osteoclasts, and regulation of bone resorption. This study aimed to evaluate the use of the salivary soluble RANKL (sRANKL)/OPG ratio as a diagnostic marker for periodontitis in nonsmokers. METHODS: Twenty five patients with chronic periodontitis and 25 individuals with a healthy periodontium were enrolled in this study. Samples containing 5 mL of unstimulated saliva were obtained from each subject. Salivary sRANKL and OPG concentrations were determined using a standard enzyme-linked immunosorbent assay. Statistical analysis was performed using SPSS ver. 18.0. RESULTS: The levels of sRANKL and OPG were detectable in all of the samples. Positive relationships were found between the plaque index and clinical attachment level and both the salivary concentration of sRANKL and the salivary sRANKL/OPG ratio (P<0.05). The salivary concentration of sRANKL and the sRANKL/OPG ratio were significantly higher in the periodontitis group than in the healthy group (P=0.004 and P=0.001, respectively). In contrast, the OPG concentration showed no significant differences between the groups (P=0.455). CONCLUSIONS: These findings suggest that the salivary sRANKL/OPG ratio may be helpful in the screening and diagnosis of periodontitis. However, longitudinal studies with larger populations are needed to confirm these results. PMID- 24236246 TI - Comparative volumetric and clinical evaluation of peri-implant sulcular fluid and gingival crevicular fluid. AB - PURPOSE: Peri-implant sulcular fluid (PISF) has a production mechanism similar to gingival crevicular fluid (GCF). However, limited research has been performed comparing their behavior in response to inflammation. Hence, the aim of the present study was to comparatively evaluate PISF and GCF volume with varying degrees of clinical inflammatory parameters. METHODS: Screening of patients was conducted. Based on the perimucosal inflammatory status, 39 loaded implant sites were selected from 24 patients, with equal numbers of sites in healthy, peri implant mucositis, and peri-implantitis subgroups. GCF collection was done from age- and sex-matched dentate patients, selected with gingival inflammatory status corresponding to the implant sites. Assessment of the inflammatory status for dental/implant sites was performed using probing depth (PD), plaque index/modified plaque index (PI/mPI), gingival index/simplified gingival index (GI/sGI), and modified sulcular bleeding index (BI). Sample collection was done using standardized absorbent paper strips with volumetric evaluation performed via an electronic volume quantification device. RESULTS: Positive correlation of the PISF and GCF volume was seen with increasing PD and clinical inflammatory parameters. A higher correlation of GCF with PD (0.843) was found when compared to PISF (0.771). PISF expressed a higher covariation with increasing grades of sGI (0.885), BI (0.841), and mPI (0.734), while GCF established a moderately positive correlation with GI (0.694), BI (0.696), and PI (0.729). CONCLUSIONS: Within the limitations of this study, except for minor fluctuations, GCF and PISF volumes demonstrated a similar nature and volumetric pattern through increasing grades of inflammation, with PISF showing better correlation with the clinical parameters. PMID- 24236247 TI - Segmental osteotomy for mobilization of dental implant. AB - PURPOSE: The aim of this work is to evaluate a surgical technique for mobilization of mal posed dental implant in anterior area. METHODS: A 38-year-old patient consulted our unit for esthetic dissatisfaction with the implant treatment of a central incisor. An implant was observed in 11 and 21, where 11 was 3 mm above the ideal limit, with excessive vestibular angulation. The choice was made to perform a segmental osteotomy and mobilize the bone block and the implant down and forward; a bone block extracted from the mandibular ramus was installed between the implant block and the bed to stabilize the segment. RESULTS: After 4 months, a conventional fixed prosthesis was created and the esthetic result achieved was close to what the patient wanted, with no need for further surgery. The surgical condition was stabilized and maintained for the long-time and no complications how necrosis, infection or bone defects was present. CONCLUSIONS: It was concluded that the procedure is efficient, and the biological arguments in favor of the procedure are discussed. PMID- 24236250 TI - A letter of condolences. PMID- 24236248 TI - Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast. AB - BACKGROUND: Limonene, a major component in citrus oil, has demonstrated anti cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. MATERIALS AND METHODS: We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. RESULTS: The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. CONCLUSIONS: Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women. PMID- 24236249 TI - Maternal Hypothyroidism and Pregnancy Loss: Awaiting Firm Recommendations on Testing and Treatment. PMID- 24236251 TI - Prosody processing of korean language in stroke patients: a preliminary study. AB - OBJECTIVE: To investigate the hemispheric contributions to prosody recognitions and interference effects of semantic processing on prosody for stroke patients by using the Korean language. METHODS: Ten right hemisphere damaged patients (RHD), nine left hemisphere damaged patients (LHD), and eleven healthy controls (HC) participated. In pure prosody recognition task, four semantically neutral sentences were selected and presented in both sad and happy prosodies. In interference task, participants listened to emotionally intoned sentences in which the semantic contents were congruent or incongruent with prosody. Participants were asked to rate the valence of prosody while ignoring the semantic contents, and thus, reaction time and accuracy were estimated. RESULTS: In pure prosody recognition task, RHD showed low accuracy as compared to HC (p=0.013), and the tendency of group response showed that RHD performed worse than HC and LHD with regards to accuracy and reaction time. In interference task, analysis of accuracy revealed a significant main effect of groups (p=0.04), and the tendency implied that RHD is less accurate as compared to LHD and HC. The RHD took longer reaction times than HC in congruent and incongruent items (p<0.001). CONCLUSION: Right hemispheric laterality to prosody processing of Korean language in stroke patients was observed. Interference effects of semantic contents to prosody processing were not observed, which suggested unique characteristics of prosody for Korean language. These results could be referred as preliminary data for future researches on Korean languages. PMID- 24236252 TI - Contributing factors analysis for the changes of the gross motor function in children with spastic cerebral palsy after physical therapy. AB - OBJECTIVE: To investigate the factors which contribute to the improvements of the gross motor function in children with spastic cerebral palsy after physical therapy. METHODS: The subjects were 45 children with spastic cerebral palsy with no previous botulinum toxin injection or operation history within 6 months. They consisted of 24 males (53.3%) and 21 females (46.7%), and the age of the subjects ranged from 2 to 6 years, with the mean age being 41+/-18 months. The gross motor function was evaluated by Gross Motor Function Measure (GMFM)-88 at the time of admission and discharge, and then, the subtractions were correlated with associated factors. RESULTS: The GMFM-88 was increased by 7.17+/-3.10 through 52+/-16 days of physical therapy. The more days of admission, the more improvements of GMFM-88 were attained. The children with initial GMFM-88 values in the middle range showed more improvements in GMFM-88 (p<0.05). The children without dysphagia and children with less spasticity of lower extremities also showed more improvements in GMFM-88 (p<0.05). CONCLUSION: We can predict the improvements of the gross motor function after physical therapy according to the days of admission, initial GMFM-88, dysphagia, and spasticity of lower extremities. Further controlled studies including larger group are necessary. PMID- 24236253 TI - Treatment Effects of Ultrasound Guide Selective Nerve Root Block for Lower Cervical Radicular Pain: A Retrospective Study of 1-Year Follow-up. AB - OBJECTIVE: To compare the long-term effects and advantages of ultrasound (US) guided selective cervical nerve root block with fluoroscopy (FL)-guided transforaminal block. METHODS: From March 2009 to November 2012, 162 patients received steroid injections for lower cervical radicular pain. A total of 114 patients fulfilled the inclusion criteria. All procedures were performed by using US or FL. We compared the intravascular injections during the procedure with the effects and functional scales at 3, 6, and 12 months after the procedure between the two groups. Successful treatments occurred when patients obtained significant pain reliefs (as measured by >50% improvements in the verbal numerical scale [VNS] score and >40% improvements in the neck disability index [NDI] score) and reported a patient satisfaction score of 3 or 4 points at 12 months after the injection. Image analysis of intravascular injection and chart review were performed. Logistic regression was performed to reveal the correlations between successful treatments and variables (patient's age, gender, duration of the disease, cause, injection method, and radiologic finding). RESULTS: The VNS and NDI improved 3 months after the injection and continued to improve until 12 months for both groups. But there were no statistical differences in changes of VNS, NDI, and effectiveness between these two groups. The proportion of patients with successful treatment is illustrated as 62.5% in US-guided group and 58% in FL-guided group at 12 months. There were no significant differences between the groups or during follow-up periods. Three cases of the intravascular injections were done in FL-guided group. CONCLUSION: The US-guided selective cervical nerve root blocks are facilitated by identifying critical vessels at unexpected locations relative to the foramen and to protect injury to such vessels, which is the leading cause of reported complications from FL-guided transforaminal blocks. On treatment effect, significant long-term improvements in functions and pain reliefs were observed in both groups after the intervention. However, significant differences were not observed between the groups. Therefore, the US-guided selective cervical nerve root block was shown to be as effective as the FL-guided transforaminal block in pain reliefs and functional improvements, in addition to the absence of radiation and protection vessel injury at real-time imaging. PMID- 24236254 TI - Effects of subacromial bursa injection with corticosteroid and hyaluronidase according to dosage. AB - OBJECTIVE: To evaluate effects of subacromial bursa injection with steroid according to dosage and to investigate whether hyaluronidase can reduce steroid dosage. METHODS: Thirty patients with periarticular shoulder disorder were assigned to receive subacromial bursa injection once a week for two consecutive weeks. Ten patients (group A) underwent subacromial bursa injection with triamcinolone 20 mg; another group of ten patients (group B) with hyaluronidase 1,500 IU and triamcinolone 20 mg; and the other ten patients (group C) with triamcinolone 40 mg. We examined the active range of motion (AROM) of the shoulder joint, visual analogue scale (VAS), and shoulder disability questionnaire (SDQ) at study entry and every week until 1 week after the 2nd injection. RESULTS: All groups showed statistically significant improvements in VAS after 1st and 2nd injections. When comparing the degree of improvement in VAS, there were statistically significant differences between groups C and A or B, but not between groups A and B. SDQ was statistically significantly improved only in groups B and C, as compared to pre-injection. There were statistically significant differences in improvement of SDQ after the 2nd injection between groups C and A or B. Statistically significant improvements in AROM were shown in abduction (groups B and C) and in flexion (group C only). CONCLUSION: Repeated high-dose (40 mg) steroid injection was more effective in terms of pain relief and functional improvements of shoulder joint than medium-dose (20 mg) steroid injection in periarticular disorder. Hyaluronidase seems to have little additive effect on subacromial bursa injection for reducing the dosage of steroid. PMID- 24236255 TI - Spinal mobility, vertebral squaring, pulmonary function, pain, fatigue, and quality of life in patients with ankylosing spondylitis. AB - OBJECTIVE: To investigate the relationships between spinal mobility, pulmonary function, structural change of the spine, pain, fatigue, and quality of life (QOL) in patients with ankylosing spondylitis (AS). METHODS: Thirty-six patients with AS were recruited. Their spinal mobility was examined through seven physical tests: modified Schober test, lateral bending, chest expansion, occiput to wall, finger to ground, bimalleolar distance, and range of motion (ROM) of the spine. Pulmonary Function Test (PFT) was performed using a spirometer, and vertebral squaring was evaluated through the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). QOL, disease activity, functional capacity, and fatigue were evaluated by SF-36 Health Survey (SF-36), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Multidimensional Assessment of Fatigue (MAF) scale, respectively. Perceived physical condition and degree of pain were assessed using 10 cm visual analogue scale. RESULTS: Participants showed reduced spinal mobility, which was negatively correlated with mSASSS. PFT results showed reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) and increased FEV1/FVC. Reduced FEV1 and FVC showed positive correlations with reduced spinal mobility and a negative relationship with mSASSS. Perceived physical condition and degree of pain were both significantly related to the SF 36, BASDAI, BASFI, and MAF scores. CONCLUSION: This study shows that both reduced spinal mobility and radiographic changes in the vertebral body may have a predictive value for pulmonary impairment in patients with AS. Likewise, pain and perceived physical condition may play an important role in the QOL, functional capacity, and fatigue level of these patients. PMID- 24236256 TI - Ultrasonographic evaluation of therapeutic effects of complex decongestive therapy in breast cancer-related lymphedema. AB - OBJECTIVE: To evaluate the usefulness of ultrasonography as a follow-up tool for evaluating the effects of complex decongestive physiotherapy (CDPT) in breast cancer-related lymphedema (BCRL). METHODS: Twenty patients with BCRL were enrolled in this study. All patients had undergone therapy in the CDPT program for 2 weeks. Soft tissue thickness of both the affected and unaffected upper limb was measured before and after CDPT. The measurements were taken at 3 points (the mid-point between the medial and lateral epicondyles at the elbow level, 10 cm proximal and 10 cm distal to the elbow) with and without pressure. We then calculated the compliance of soft tissue before and after CDPT. Circumferences of both the affected and unaffected upper limb were also measured before and after CDPT at the 3 defined points. RESULTS: After 2 weeks of the CDPT program, the circumference and soft tissue thickness of the unaffected upper limb did not significantly change. In the affected upper limb, the circumference was significantly reduced in the 3 point, when compared with measurements taken prior to treatment. Additionally, soft tissue thickness was significantly reduced at the elbow and 10 cm proximal to the elbow. After CDPT, compliance at each of the 3 points had increased, but this trend was not significantly different. CONCLUSION: Our results showed that arm circumference and ultrasonography-derived soft tissue thickness was useful as a way of assessing therapeutic effects of CDPT. PMID- 24236257 TI - Long-term effects of complex decongestive therapy in breast cancer patients with arm lymphedema after axillary dissection. AB - OBJECTIVE: To investigate the long-term effects of complex decongestive therapy (CDT) on edema reduction in breast cancer-related lymphedema patients after axillary dissection, according to the initial volume of edema. METHODS: A retrospective review of 57 patients with unilateral arm after an axillary dissection for breast cancer was performed. The patients, treated with two weeks of CDT and self-administered home therapy, were followed for 24 months. Arm volume was serially measured by using an optoelectronic volumeter prior to and immediately after CDT; and there were follow-up visits at 3, 6, 12, and 24 months. Patients were divided into two groups according to the percent excess volume (PEV) prior to CDT: group 1, PEV<20% and group 2, PEV>=20%. RESULTS: In group 1, mean PEV before CDT was 11.4+/-5.0% and 14.1+/-10.6% at 24 months after CDT with no significant difference. At the end of CDT, PEV was 28.8+/-15.7% in group 2, which was significantly lower than the baseline (41.9+/-19.6%). The reduction of PEV was maintained for 24 months in group 2. CONCLUSION: The long term effects of CDT were well-maintained for 24 months, but there was a difference in progression of PEV between the two groups. The patients with more initial PEV showed significant volume-reducing effects of CDT. In patients with less initial PEV, the severity of lymphedema did not progress to higher grades. PMID- 24236258 TI - Reliability and Validity of the Korean Version VISA-P Questionnaire for Patellar Tendinopathy in Adolescent Elite Volleyball Athletes. AB - OBJECTIVE: To translate the English Victorian Institute of Sport Assessment for patellar tendinopathy (VISA-P) questionnaire into a Korean version and to determine the reliability and validity of the Korean version. METHODS: The English VISA-P questionnaire was translated into Korean according to the internationally recommended guidelines. Then, 28 adolescent elite volleyball athletes (average age, 16 years; range, 14 to 19 years) were asked to complete the questionnaire three times (before examination, after examination, and 1 week later) for reliability. They were evaluated through a physical examination and ultrasonography to diagnosis patellar tendinopathy. RESULTS: The internal consistency of the VISA-P questionnaire by Cronbach's alpha was 0.80 for the first, 0.78 for the second, and 0.79 for the third assessment. The intraclass correlation coefficient (ICC) between the first and second assessments was 0.97. The ICC between the second and third assessments was 0.96. The mean VISA-P scores were 67.6+/-15.7 for the patellar tendinopathy group (n=23) and 92.6+/-8.6 for the normal group (n=5). There were significantly lower VISA-P scores in the patellar tendinopathy group compared to the normal group. CONCLUSION: The translated Korean version VISA-P questionnaire has good internal consistency, test-retest reliability and validity. In addition, this study indicated that most adolescent elite volleyball athletes had patellar tendon problems. Therefore, the Korean version VISA-P is a useful self-administered outcome score of athletes with patellar tendinopathy. PMID- 24236259 TI - Degenerative changes of spine in helicopter pilots. AB - OBJECTIVE: To determine the relationship between whole body vibration (WBV) induced helicopter flights and degenerative changes of the cervical and lumbar spine. METHODS: We examined 186 helicopter pilots who were exposed to WBV and 94 military clerical workers at a military hospital. Questionnaires and interviews were completed for 164 of the 186 pilots (response rate, 88.2%) and 88 of the 94 clerical workers (response rate, 93.6%). Radiographic examinations of the cervical and the lumbar spines were performed after obtaining informed consent in both groups. Degenerative changes of the cervical and lumbar spines were determined using four radiographs per subject, and diagnosed by two independent, blinded radiologists. RESULTS: There was no significant difference in general and work-related characteristics except for flight hours and frequency between helicopter pilots and clerical workers. Degenerative changes in the cervical spine were significantly more prevalent in the helicopter pilots compared with control group. In the cervical spine multivariate model, accumulated flight hours (per 100 hours) was associated with degenerative changes. And in the lumbar spine multivariate model, accumulated flight hours (per 100 hours) and age were associated with degenerative changes. CONCLUSION: Accumulated flight hours were associated with degenerative changes of the cervical and lumbar spines in helicopter pilots. PMID- 24236260 TI - Grisel syndrome: pathophysiological evidence from magnetic resonance imaging findings. AB - Grisel syndrome is a condition of uncertain etiology characterized by a non traumatic atlantoaxial subluxation following an infection in the head and neck region. Although first described in 1830, the exact pathophysiology of Grisel syndrome remains unclear. We present a case of atlantoaxial subluxation after acute lymphadenitis diagnosed with a dynamic computed tomography (CT) and magnetic resonance imaging (MRI). A previously healthy 9-year-old male patient presented with torticollis of sudden onset. Dynamic CT and MR imaging showed rotary atlantoaxial subluxation and inflammation surrounding the cervical spinal ligaments. A follow-up MRI of the cervical spine, taken 3 weeks after the onset of symptoms, showed a complete resolution of subluxation and inflammation surrounding the cervical spinal ligaments. In this case report, we support the hypothesis that an inflammation-induced laxity of the cervical ligaments is the pathologic key to Grisel syndrome using radiologic findings. PMID- 24236261 TI - Anterior cervical osteophytes causing Dysphagia and paradoxical vocal cord motion leading to dyspnea and dysphonia. AB - Anterior cervical osteophytes are common and usually asymptomatic in elderly people. Due to mechanical compressions, inflammations, and tissues swelling of osteophytes, patients may be presented with multiple complications, such as dysphagia, dysphonia, dyspnea, and pulmonary aspiration. Paradoxical vocal cord motion is an uncommon disease characterized by vocal cord adductions during inspiration and/or expiration. This condition can create shortness of breath, wheezing, respiratory stridor or breathy dysphonia. We report a rare case demonstrating combined symptoms of dyspnea, dysphonia as well as dysphagia at the same time in a patient with asymptomatic anterior cervical osteophytes. Moreover, this is the first report demonstrating that anterior osteophytes can be a possible etiological factor for paradoxical vocal cord motion that induces serious respiratory symptoms. PMID- 24236262 TI - Intractable abdominal pain in a patient with spinal cord injury: a case report. AB - Patients with spinal cord injury (SCI) may experience several types of chronic pains. Abdominal pain in patients with SCI has gained limited attention and little is yet known about its characteristics and mechanisms. It often has been regarded as visceral pain associated with constipation and distention. Neuropathic pains localized in the abdomen have rarely been reported. We experience a case of intractable abdominal pain in a patient with SCI, neither of visceral pathology nor of musculoskeletal origin. The nature of pain fulfilled the diagnostic criteria for neuropathic pains. The pain was therefore regarded as neuropathic and managed accordingly. The first- and second-line oral drugs available were being performed, unfortunately, adequate pain control was not achieved. We tried an intrathecal lidocaine injection as another treatment option, and the injection had considerable effects. PMID- 24236263 TI - Thoracic infectious spondylitis after surgical treatments of herniated lumbar intervertebral disc. AB - The postoperative infectious spondylitis has been reported to occur among every 1% to 12%. It is difficult to early diagnose in some cases. If the diagnosis is delayed, it can be a life-threatening condition. We report a 32-year-old male patient with postoperative infectious spondylitis. He had surgical treatments for traumatic intervertebral disc herniations in L3-4 and L4-5. Three weeks after surgery, he complained for fever and paraplegia. Cervicothoracic magnetic resonance imaging showed the collapsed T2 and T3 vertebral body with changes of bone marrow signal intensity. Moreover, it showed anterior and posterior epidural masses causing spinal cord compressions which suggested infectious spondylitis. After the use of antibiotics and surgical decompressions T2-T3, his general conditions were improved and muscle power of lower extremities began to be gradually restored. However, we could not identify the exact organisms that may be the cause of infectious spondylitis. It could be important that the infectious spondylitis, which is presented away from the primary operative level, should be observed in patients with fevers of unknown origin and paraplegia. PMID- 24236264 TI - Application of percutaneous cervical nucleoplasty using the navigable disc decompression device in patient of cervical herniated intervertebral disc: a case report. AB - Recent years, various percutaneous procedures including cervical nucleoplasty have been developed for disc decompressions to relieve radicular pains caused by disc herniations. We report the application of percutaneous cervical nucleoplasty (PCN) by using the navigable disc decompression device in two patients of cervical herniated intervertebral discs (HIVD). A 38-year-old female diagnosed with C4-C5 disc extrusion with bilateral C5 roots impingement received nucleoplasty twice at C4-C5 disc level. After second procedure, her pain was improved from 6-7/10 to 1-2/10 by visual analog scale (VAS). The second case, a 51-year-male was diagnosed with C6-C7 disc extrusion with right C7 roots impingement and received the procedure at C6-C7 disc level. The pain improved from 8/10 to 3-4/10 by VAS. Successfully, we decompressed cervical herniated discs in 2 HIVD patients without major complications. The PCN with the navigable device will be recommended as an alternative treatment method for cervical HIVD. PMID- 24236265 TI - Supplementary motor area syndrome and flexor synergy of the lower extremities. AB - Clinical presentation of supplementary motor area (SMA) syndrome includes complete akinesia of the contralateral side of the body and mutism, with secondary recovery of neurologic deficit. Multi-joint coordination is frequently impaired following the development of a brain lesion and is generally restricted by abnormal patterns of muscle activation within the hemiparetic limb, clinically termed muscle synergies. However, no work to date has confirmed this observation with the aid of objective methods, such as gait analysis, and the development of reflex pattern has not been suggested as a possible cause. We describe two unusual cases of flexor synergy after tumor resection of SMA lesions. PMID- 24236266 TI - Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant? AB - Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia. PMID- 24236267 TI - Syringomyelia coexisting with guillain-barre syndrome. AB - Guillain-Barre syndrome (GBS) and syringomyelia are diseases of different entities. GBS is an acute post-infectious autoimmune disease which is mediated by autoantibodies against the myelin of peripheral nerves. Syringomyelia is a chronic disease characterized by a cavity extending longitudinally inside the spinal cord. A 67-year-old man is being hospitalized due to severe numbness and ascending weakness in all limbs. On neurological examination, the motor power of all limbs are decreased and show absence of deep tendon reflexes (DTRs). The patient is being diagnosed with GBS on the basis of the acute clinical course, nerve conduction studies of segmental demyelinating polyneuropathy, and a finding of albuminocytologic dissociation in the cerebrospinal fluid. The patient is presented with a new set of symptoms thereafter, which composes of sensory changes in the upper extremities, the urinary dysfunction including frequency and residual urine, spastic bilateral lower extremities, and increased reflexes of the knee and the biceps at follow-up examinations. The spinal magnetic resonance imaging in the sagittal section revealed a syrinx cavity between the fifth cervical and the first thoracic vertebral segment in the cord. The somatosensory evoked potential show sensory pathway defects between both the brachial plexus and the brain stem. Thus, this patient is being diagnosed with both GBS and syringomyelia. We report a case of symptomatic syringomyelia coexisting with GBS. Since the GBS is presented with a progressive muscle weakness and reduced DTRs, the muscle weakness and stiffness in the extremities suggests a concurrent syringomyelia might be easily overlooked. PMID- 24236268 TI - Recurrent cerebral infarction caused by mobile aortic arch thrombus refractory to warfarin therapy. AB - The mobile thrombus in the aortic arch is a rare condition, which becomes rarer when associated with cerebral infarction, resulting in disabling complications. Transesophageal echocardiography is useful for detecting the source of thrombi in the heart and aortic arch. Here, we report a case of a patient who suffered from recurrent cerebral infarction four times during the previous 18 months due to mobile thrombus in the aortic arch despite anticoagulant therapy. The thrombus with rocking motion (9.6 and 8 mm) was laid in the top of the aortic arch, and surgical resection was not allowed due to the location. We began anticoagulation therapy initially with heparin followed by a combination of warfarin, aspirin, and atorvastatin with an international normalized ratio between 2 and 3. The size of the aortic thrombi was significantly decreased by 3 mm and stabilized after 18 months. PMID- 24236271 TI - Dialectical Behaviour Therapy for the Treatment of Emotion Dysregulation and Trauma Symptoms in Self-Injurious and Suicidal Adolescent Females: A Pilot Programme within a Community-Based Child and Adolescent Mental Health Service. AB - Background. The literature suggests a link between childhood trauma and maladaptive emotion regulation strategies, including nonsuicidal self-injury (NSSI) and suicidality. We assessed the impact of a pilot dialectical behaviour therapy (DBT) programme on reducing trauma-related symptoms and improving emotional regulation, suicidality, and NSSI in adolescents. Methods. Six adolescents attending a community mental health service received 26 weeks of DBT, together with a parent. Independent assessors collected measures on each participant at baseline, posttreatment, and three-month followup. We implemented further improvements over past research with the use of adolescent-specific outcome measures as well as independent assessment of treatment integrity, noted as problematic in previous studies, using videotapes. Results. Firstly, adolescents reported a decrease in trauma-based symptoms, suicidality, and NSSI following participation in the DBT programme that was maintained at the three month followup. Secondly, adolescents also reported improved emotion regulation immediately following treatment, and this was maintained, albeit more moderately, three months later. Given the burgeoning demand on mental health services, it is notable that five of the six adolescents were discharged from the service following the DBT intervention. Conclusions. The results of this pilot programme suggest that DBT has the potential to improve the symptoms of this at-risk population. PMID- 24236272 TI - Working memory training in patients with chronic schizophrenia: a pilot study. AB - Background. There is evidence that patients with schizophrenia suffer from decline in working memory performance with consequences for psychosocial outcome. Objective. To evaluate the efficacy of a computerized working memory training program (BrainStim) in patients with chronic schizophrenia. Methods. Twenty-nine inpatients with chronic schizophrenia were assigned to either the intervention group receiving working memory training (N = 15) or the control group without intervention (N = 14). Training was performed four times a week for 45 minutes during four weeks under neuropsychological supervision. At baseline and followup all participants underwent neuropsychological testing. Results. Pre-post comparisons of neuropsychological measures showed improvements in visual and verbal working memories and visual short-term memory with small and large effect sizes in the intervention group. In contrast, the control group showed decreased performance in verbal working memory and only slight changes in visual working memory and visual and verbal short-term memories after 4 weeks. Analyses of training profiles during application of BrainStim revealed increased performance over the 4-week training period. Conclusions. The applied training tool BrainStim improved working memory and short-term memory in patients with chronic schizophrenia. The present study implies that chronic schizophrenic patients can benefit from computerized cognitive remediation training of working memory in a clinical setting. PMID- 24236273 TI - Proposed Diagnostic Criteria for the DSM-5 of Nonsuicidal Self-Injury in Female Adolescents: Diagnostic and Clinical Correlates. AB - Nonsuicidal self-injury (NSSI) is included as conditions for further study in the DSM-5. Therefore, it is necessary to investigate the proposed diagnostic criteria and the diagnostic and clinical correlates for the validity of a diagnostic entity. The authors investigated the characteristics of NSSI disorder and the proposed diagnostic criteria. A sample of 73 female inpatient adolescents and 37 nonclinical adolescents (aged 13 to 19 years) was recruited. Patients were classified into 4 groups (adolescents with NSSI disorder, adolescents with NSSI without impairment/distress, clinical controls without NSSI, and nonclinical controls). Adolescents were compared on self-reported psychopathology and diagnostic cooccurrences. Results indicate that adolescents with NSSI disorder have a higher level of impairment than adolescents with other mental disorders without NSSI. Most common comorbid diagnoses were major depression, social phobia, and PTSD. There was some overlap of adolescents with NSSI disorder and suicidal behaviour and borderline personality disorder, but there were also important differences. Results further suggest that the proposed DSM-5 diagnostic criteria for NSSI are useful and necessary. In conclusion, NSSI is a highly impairing disorder characterized by high comorbidity with various disorders, providing further evidence that NSSI should be a distinct diagnostic entity. PMID- 24236274 TI - Cognitive aspects of hyperactivity and overactivity in preadolescents with tourette syndrome. AB - Attention deficit disorder with hyperactivity (ADHD) is a common comorbidity in children with Tourette syndrome (TS). However, motor restlessness and high levels of sensorimotor activation or "overactivity" may be a feature of TS rather than a distinct ADHD comorbidity. The link between overactivity and ADHD in TS has yet to be established and in particular between adult and preadolescent manifestations. The current study furthers this understanding of ADHD features in TS by investigating the relationship between cognitive and behavioral aspects of ADHD and TS. The style of planning (STOP) overactivity scale was compared in preadolescent (n = 17) and adult (n = 17) samples. The STOP overactivity scale measures the characteristic overactive style of planning in everyday life. The aims of the study were twofold as follows: (1) to see if an overactive style was present in adolescents as well as in adults, and (2) to see if this overactive style correlated with hyperactivity, impulsivity, or perfectionism. Results suggest that overactivity may be a better description of the hyperactivity manifestations in TS. Behavioral components of overactivity were present in preadolescents while the cognitive components were more frequent in adults. Overactivity relates at the same time to perfectionism and impulsivity. PMID- 24236275 TI - The Effect of Family Factors on Intense Alcohol Use among European Adolescents: A Multilevel Analysis. AB - In Europe use of alcohol by adolescents is a large and increasing problem. The aim of this study is to examine the effects of family factors such as structure, social control, affluence, and negative life events on adolescents' risky alcohol use. Data on alcohol use and family factors were obtained from the International Self-Report Delinquency Study (ISRD-2). Using multilevel analysis, it was found that overall, complete family and high social control by parents were lowering the intense alcohol use whereas negative life events in the family and high family affluence were increasing youngsters' intense alcohol use. Differences between regions of Europe were present for all family factors except affluence. Namely, in Northern Europe the impact of family structure and social control on intense alcohol use was stronger than that in other regions (e.g., Western Europe, Mediterranean, and Postsocialist countries). Also, in Northern Europe where the proportion of adolescents who have not experienced negative life events is the highest, the impact of negative life events on intense alcohol use was stronger; that is, negative life events increased the alcohol use. We conclude that family plays a significant role in adolescents' risky alcohol use. PMID- 24236276 TI - Social anxiety, tremor severity, and tremor disability: a search for clinically relevant measures. AB - Background. While social anxiety has been reported among essential tremor (ET) patients, very little is known about the relation between self-report measures of social anxiety, tremor severity and disability, and cognition. Methods. Sixty three individuals diagnosed with ET took part in a comprehensive study examining neurocognition and behavioral functioning. A psychiatric diagnostic interview, three social anxiety questionnaires, and an idiographic-based behavioral assessment to pinpoint anxiety provoking situations and related distress were completed. Results. Thirty percent of the participants met diagnostic criteria for social anxiety disorder (SAD). Social anxiety questionnaires were negligibly related to tremor severity and disability. Idiographic behavioral assessment of subjective distress was moderately related to resting tremor severity and disability and strongly related to social anxiety questionnaires scores. Only one cognitive variable was related to tremor severity. Conclusions. These findings suggest that (a) self-report measures of social anxiety with ET patients may underestimate distress; (b) emphasis on tremor severity may be misleading; (c) tremor disability may be a more sensitive and functional measure related to cognition and effect; (d) SAD is wide spread and does not appear to be related to dysregulated executive function; and (e) development of an ET-specific measure of social anxiety is called for. PMID- 24236277 TI - Trends in Video Game Play through Childhood, Adolescence, and Emerging Adulthood. AB - This study explored the relationship between video gaming and age during childhood, adolescence, and emerging adulthood. It also examined whether "role incompatibility," the theory that normative levels of substance use decrease through young adulthood as newly acquired adult roles create competing demands, generalizes to video gaming. Emerging adult video gamers (n = 702) recruited from video gaming contexts in New York City completed a computer-assisted personal interview and life-history calendar. All four video gaming indicators-days/week played, school/work day play, nonschool/work day play, and problem play-had significant curvilinear relationships with age. The "shape" of video gaming's relationship with age is, therefore, similar to that of substance use, but video gaming appears to peak earlier in life than substance use, that is, in late adolescence rather than emerging adulthood. Of the four video gaming indicators, role incompatibility only significantly affected school/work day play, the dimension with the clearest potential to interfere with life obligations. PMID- 24236278 TI - Dimensions of Attitudes towards the Mentally Ill in the General Population Stability and Change over Time at Urban and Rural Sites. AB - Items measuring attitudes toward the mentally ill can be limited in relevance to a particular period or place. The main objective of the study was to provide evidence toward a questionnaire that was short and psychometrically stable over time and geography, and that could be used within comprehensive mental health surveys of general populations. Four rural samples, Lofoten 1983 (n = 470), 1990 (n = 947), 2000 (n = 864), and Valdres 2010 (n = 772), and two urban samples, Oslo 1990 (n = 948) and 2000 (n = 467), were used to test this. The questionnaire was self-administered with fixed questions and response alternatives. Using the three Lofoten and the two Oslo samples, the stability of the factor analytic structure of 19 attitude items was established. In all analyses, there was a clear leveling off after three factors. The 13 highest loading items on these three factors were used in a new rural region, Valdres, in 2010. The three established factors/dimensions, named Distance, Demands, and Positive, seemed to be reasonably stable within a variety of Norwegian samples. On the other hand, the analyses were different enough to recommend researchers and politicians to be careful when comparing absolute levels of the suggested indexes across different locations and at different points in time. PMID- 24236279 TI - Impact of Multiplayer Online Role-Playing Games upon the Psychosocial Well-Being of Adolescents and Young Adults: Reviewing the Evidence. AB - Introduction. For many people, the online environment has become a significant arena for everyday living, and researchers are beginning to explore the multifaceted nature of human interaction with the Internet. The burgeoning global popularity and distinct design features of massively multiplayer online role playing games (MMORPGs) have received particular attention, and discourses about the phenomenon suggest both positive and negative impact upon gamer health. Aim. The purpose of this paper was to critically appraise the research literature to determine if playing MMORPGs impacts upon the psychosocial well-being of adolescents and young adults. Method. Initial searches were conducted on nine databases spanning the years 2002 to 2012 using key words, such as online gaming, internet gaming, psychosocial, and well-being, which, in addition to hand searching, identified six studies meeting the inclusion and exclusion criteria for this review. Results. All six studies strongly associated MMORPG playing with helpful and harmful impact to the psychosocial well-being of the populations under study; however due to the methodologies employed, only tentative conclusions may be drawn. Conclusion. Since both helpful and harmful effects were reported, further multidisciplinary research is recommended to specifically explore the clinical implications and therapeutic potentialities of this modern, growing phenomenon. PMID- 24236280 TI - Future Intent to Run and Running Performance of Students Exposed to a Traditional versus an Autonomy Supportive Motivational Running Program. AB - Background. The study's primary purpose was to investigate whether an autonomy supportive motivational climate in a running program would increase future running intent among high school students. A secondary purpose was to examine whether the program would increase individual performance in the Cooper 12-minute run. Methods. Students participated in a 4-month running intervention program which included four timed runs, one per month, and a future intent questionnaire prior to the start of the timed runs and following the last run. Results. Factorial repeated measures ANOVA revealed significance regarding future intent (P = .026) at both schools. Factorial repeated measures ANOVA indicated differences between the runs at both schools (P < .001). Paired samples t-tests were conducted to look at significance with paired runs. Results revealed significance in two of the six pairs at the treatment school, notably between the first and last timed runs (P = .004). Only one pair was found to be significant (P < .001) with the control school. Conclusion. At both schools, the overall number of laps increased as well as future intent to run scores. The results do not support evidence of a greater effect from the autonomy supportive environment over a traditional environment. PMID- 24236281 TI - Screening for Bipolar Disorder Symptoms in Depressed Primary Care Attenders: Comparison between Mood Disorder Questionnaire and Hypomania Checklist (HCL-32). AB - Objective. To describe the prevalence of patients who screen positive for bipolar disorder (BD) symptoms in primary care comparing two screening instruments: Mood Disorders Questionnaire (MDQ) and Hypomania Checklist (HCL-32). Participants. Adult patients presenting to their primary care practitioners for any cause and reporting current depression symptoms or a depressive episode in the last 6 months. Methods. Subjects completed MDQ and HCL-32, and clinical diagnosis was assessed by a psychiatrist following DSM-IV criteria. Depressive symptoms were evaluated in a subgroup with the Patient Health Questionnaire (PHQ-9). Results. A total of 94 patients were approached to participate and 93 completed the survey. Among these, 8.9% screened positive with MDQ and 43.0% with HCL-32. MDQ positive had more likely features associated with BD: panic disorder and smoking habit (P < .05). The best test accuracy was performed by cut-off 5 for MDQ (sensitivity = .91; specificity = .67) and 15 for HCL-32 (sensitivity = .64; specificity = .57). Higher total score of PHQ-9 was related to higher total scores at the screening tests (P < .001). Conclusion. There is a significant prevalence of bipolar symptoms in primary care depressed patients. MDQ seems to have better accuracy and feasibility than HCL-32, features that fit well in the busy setting of primary care. PMID- 24236282 TI - Cognitive performance in a subclinical obsessive-compulsive sample 1: cognitive functions. AB - Individuals who are not clinically diagnosed with obsessive-compulsive disorder (OCD) but still display obsessive-compulsive (OC) tendencies may show cognitive impairments. The present study investigated whether there are subgroups within a healthy group showing characteristic cognitive and emotional performance levels similar to those found in OCD patients and whether they differ from OCD subgroups regarding performance levels. Of interest are those cases showing subclinical symptomatology. The results revealed no impairments in the subclinical OC participants on the neuropsychological tasks, while evidence suggests that there exist high and low scores on two standardised clinical instruments (Yale-Brown Obsessive Compulsive Scale and Cognitive Assessment Instrument of Obsessions and Compulsions) in a healthy sample. OC symptoms may diminish the quality of life and prolong sustainable return to work. It may be that occupational rehabilitation programmes are more effective in rectifying subclinical OC tendencies compared to the often complex symptoms of diagnosed OCD patients. The relationship between cognitive style and subclinical OC symptoms is discussed in terms of how materials and information might be processed. Although subclinical OC tendencies would not seem to constitute a diagnosis of OCD, the quality of treatment programmes such as cognitive behavioural therapy can be improved based on the current investigation. PMID- 24236283 TI - Struggling on my own: a cognitive perspective on frequent attenders' conception of life and their interaction with the healthcare system. AB - Different studies reveal that a large percentage of people frequently attending healthcare not only suffer from diffuse somatic symptoms but also from psychological distress and difficulties in dealing with everyday life. Even though they are not always diagnosed with psychiatric disease, questions arise about their mental health. The study aims at describing frequent attenders' conceptions of life, and as a result their health, from a cognitive perspective. A qualitative content analysis of in-depth interviews was carried out with nine service users in primary healthcare. The findings reveal that participants experience themselves as inadequate and as being a burden for others, by whom they experience rejection, in different ways. In order to take part in community with others the person develops compensatory strategies that aim at concealing their inadequacies, thus also preventing them from sharing their suffering with others. The consequence is that the persons become even more alienated as they start to relate to others through a facade and furthermore are unable to either improve their health or obtain adequate care. It can be concluded that these patients need to be taken seriously in order to prevent further psychological suffering. PMID- 24236284 TI - The Relationship between the UPPS-P Impulsivity Dimensions and Nonsuicidal Self Injury Characteristics in Male and Female High-School Students. AB - The present study investigated the association between nonsuicidal self-injury characteristics, functions, and the UPPS-P impulsivity-related traits in high school students using self-report questionnaires. More than 17% of the 613 students engaged in at least one type of NSSI behavior. Compared to male students, female students engaged more often in cutting and less in head banging. All NSSI behaviors were significantly related to Negative and Positive Urgency, that is, the tendency to act impulsive in the presence of negative/positive affect. Interactions between different UPPS-P impulsivity dimensions did not increase the percentage of explained variance in the different NSSI behaviors. Furthermore, severe cutting was negatively related to Lack of Premeditation. Different NSSI functions showed differential relationships with the five UPPS-P impulsivity dimensions. PMID- 24236285 TI - Factors associated with readmission of patients at a university hospital psychiatric ward in iran. AB - Objectives. Readmission has a major role in the reduction of the quality of life and the increase in the years of lost life. The main objectives of this study were to answer to the following research questions. (a) What was the readmission rate? (b) What were the social, demographic, and clinical characteristics of patients admitted to the Psychiatric Emergency Service at Nour University Hospital, affiliated to Isfahan University of Medical Sciences, Isfahan, Iran? (c) What were the effective factors on readmission? Method. This cross-sectional study was conducted on a total number of 3935 patients who were admitted to Isfahan University Hospital Psychiatric Ward in Isfahan, Iran, from 2004 to 2010. Gender, age, marital status, education, self-report history of previous admission, type of psychiatric disorder, substance misuse, suicide, and the length of the current psychiatric disorder were collected from the registered medical files of patients. The data were analysed using the negative binomial regression model. Results. We found that factors such as psychiatric anxiety disorder, bipolar I, bipolar II, psychotic disorder, depression, and self report history of previous admission were statistically significant in the number of readmissions using the negative binomial model. Conclusion. Readmission to the psychiatric ward is mainly predictable by the type of diagnosis and psychosocial supports. PMID- 24236286 TI - The effect of withdrawal and intake of nicotine on smokers' ability to ignore distractors in a number parity decision task. AB - Nicotine's attention enhancing effects are often attributed to enhancement of stimulus filtering by the attention networks. We investigated distractibility in 20 abstinent cigarette smokers (9 hours overnight; phase 1) and tested them again after smoking one cigarette (phase 2). Their performance was compared to 20 nonsmokers (no nicotine intake). In an auditory number parity decision task, participants had to make a forced choice "odd" or "even" decision about centrally presented numbers between 2 and 9, while ignoring laterally presented preceding or simultaneous novel distractors. In phase 1, distractors that preceded goal stimuli slowed reaction times (RTs) more than simultaneously presented distractors in both groups. In phase 2, nicotine intake speeded RTs in smokers in all conditions and reduced RT variability for simple number decisions and simultaneous distractors. Overall, there was a nonsignificant trend for smokers to be less accurate than nonsmokers. Accuracy in the simultaneous distractor condition decreased in both groups in phase 2. We argue that the observed nicotine-induced improvements on behavioral performance primarily reflect enhancement of top-down control of attention. PMID- 24236287 TI - Negative Symptoms of Psychosis Correlate with Gene Expression of the Wnt/beta Catenin Signaling Pathway in Peripheral Blood. AB - Genes in the Wnt (wingless)/ beta -catenin signaling pathway have been implicated in schizophrenia pathogenesis. No study has examined this pathway in the broader context of psychosis symptom severity. We investigated the association between symptom severity scores and expression of 25 Wnt pathway genes in blood from 19 psychotic patients. Significant correlations between negative symptom scores and deshivelled 2 (DVL2) (r adj = -0.70; P = 0.0008) and glycogen synthase kinase 3 beta (GSK3B) (r adj = 0.48; P = 0.039) were observed. No gene expression levels were associated with positive symptoms. Our findings suggest that the Wnt signaling pathway may harbor biomarkers for severity of negative but not positive symptoms. PMID- 24236288 TI - From sociocultural disintegration to community connectedness dimensions of local community concepts and their effects on psychological health of its residents. AB - In a series of community mental health promotion studies in Lofoten, Norway, the concept of sociocultural integration is used to describe properties of a local community that are related to people's psychological health. Starting with Durkheim's description of a cohesive society, we compare different concepts that are related to sociocultural integration, for example, sense of community, social capital, and social cohesion. We then examine the relationship of various individual oriented social psychological concepts to sociocultural integration. These concepts often share theoretical and operational definitions. The concept of sociocultural integration in the Lofoten studies was proved to be very valuable in understanding how the properties of a community can affect people's mental health and their social psychological properties. It has also shown its value in the planning of mental health services and demonstrating its success in concrete community-based mental health promotion projects. Thus they could make important contributions to further studies and actions in local communities where the intersection between the individual, their social network, and their local community occurs. PMID- 24236289 TI - Involving the family in the care and treatment of women with postpartum psychosis: Swedish psychiatrists' experiences. AB - The aim of the study was to describe Swedish psychiatrists' experiences of involving the family in the treatment of women with postpartum psychosis. A qualitative design was used, and semistructured qualitative research interviews were conducted with nine psychiatrists from the south of Sweden. Data were analysed using qualitative content analysis. Four categories were found: the family as a resource, the family as coworkers, preparing the family for the future, and the family as a burden. The result showed that the psychiatrists considered the family to be a resource to which they devoted a great deal of care and effort. It was particularly important to involve the partner, informing about the course of the illness and the steps that need to be taken in the event of a relapse and reducing any guilt feelings. The psychiatrists instilled confidence and hope for a future of health and further child bearing. The family members' limited understanding of the treatment may impede the involvement of the family. Conclusion of the study was that the goal for family involvement was to facilitate the women's care and treatment. Further studies are needed to provide suggestions on how to develop family involvement in the care of women suffering from postpartum psychosis. PMID- 24236290 TI - Age differences in the association of severe psychological distress and behavioral factors with heart disease. AB - Few studies have examined the risk factors of serious psychological distress (SPD) and behavioral factors for heart disease separately stratified as young (18 44 years), middle aged (45-64 years), and elderly (65 years or older). A total of 3,540 adults with heart disease and 37,703 controls were selected from the 2005 California Health Interview Survey. Data were weighted to be representative and adjusted for potential undercoverage and nonresponse biases. Multiple logistic regression models were used to estimate the associations of the factors with heart disease at different ages. The prevalence of SPD was 8% in cases and 4% in controls, respectively. For young adults, SPD and higher federal poverty level (FPL) were associated with an increased risk of heart disease while for middle aged adults, SPD, past smoking, lack of physical activity, obesity, male, and unemployment were associated with an increased risk of heart disease. In addition, SPD, past smoking, lack of physical activity, obesity, male, unemployment, White, and lower FPL were associated with an increased risk of heart disease in elderly. Our findings indicate that risk factors for heart disease vary across all ages. Intervention strategies that target risk reduction of heart disease may be tailored accordingly. PMID- 24236291 TI - Evaluation of NK cell function by flowcytometric measurement and impedance based assay using real-time cell electronic sensing system. AB - Although real-time cell electronic sensing (RT-CES) system-based natural killer (NK) cytotoxicity has been introduced, it has not been evaluated using human blood samples. In present study, we measured flowcytometry based assay (FCA) and RT-CES based NK cytotoxicity and analyzed degranulation activity (CD107a) and cytokine production. In 98 healthy individuals, FCA with peripheral blood mononuclear cells (PBMCs) at effector to target (E/T) ratio of 32 revealed 46.5 +/- 2.6% cytolysis of K562 cells, and 23.5 +/- 1.1% of NK cells showed increased degranulation. In RT-CES system, adherent NIH3T3 target cells were resistant to basal killing by PBMC or NK cells. NK cell activation by adding IL-2 demonstrated real-time dynamic killing activity, and lymphokine-activated PBMC (E/T ratio of 32) from 15 individuals showed 59.1 +/- 6.2% cytotoxicity results after 4 hours incubation in RT-CES system. However, there was no significant correlation between FCA and RT-CES cytotoxicity. After K562 target cell stimulation, PBMC produced profound proinflammatory and immunoregulatory cytokines/chemokines including IL-2, IL-8, IL-10, MIP-1 alpha beta , IFN- gamma , and TNF- alpha , and cytokine/chemokine secretion was related to flowcytometry-based NK cytotoxicity. These data suggest that RT-CES and FCA differ in sensitivity, applicability and providing information, and further investigations are necessary in variable clinical conditions. PMID- 24236293 TI - Design and validation of an augmented reality system for laparoscopic surgery in a real environment. AB - PURPOSE: This work presents the protocol carried out in the development and validation of an augmented reality system which was installed in an operating theatre to help surgeons with trocar placement during laparoscopic surgery. The purpose of this validation is to demonstrate the improvements that this system can provide to the field of medicine, particularly surgery. METHOD: Two experiments that were noninvasive for both the patient and the surgeon were designed. In one of these experiments the augmented reality system was used, the other one was the control experiment, and the system was not used. The type of operation selected for all cases was a cholecystectomy due to the low degree of complexity and complications before, during, and after the surgery. The technique used in the placement of trocars was the French technique, but the results can be extrapolated to any other technique and operation. RESULTS AND CONCLUSION: Four clinicians and ninety-six measurements obtained of twenty-four patients (randomly assigned in each experiment) were involved in these experiments. The final results show an improvement in accuracy and variability of 33% and 63%, respectively, in comparison to traditional methods, demonstrating that the use of an augmented reality system offers advantages for trocar placement in laparoscopic surgery. PMID- 24236294 TI - Is delayed pressure urticaria associated with increased systemic release of sCD40L? AB - BACKGROUND: Elevated levels of soluble CD40 Ligand (sCD40L) were found in serum but not in plasma of patients with chronic spontaneous urticaria (CU). What is important is that sCD40L has proinflammatory properties, and its elevated plasma level may indicate increased risk of cardiovascular events. These observations should stimulate further evaluation of sCD40L in different forms of urticaria. AIM: In the present study, sCD40L plasma level was investigated in delayed pressure urticaria (DPU). METHODS: As platelets are predominant and variable sources of sCD40L, we investigated sCD40L concentration in platelet-poor plasma (PPP), which seems the best way to minimize the potential contribution of these cells to the ligand level. RESULTS: Plasma sCD40L concentration was significantly increased in the DPU group compared to the healthy controls. CONCLUSIONS: It seems that DPU is associated with increased systemic release of sCD40L, which is believed to derive predominantly from activated platelets. The present study as well as the earlier contributions suggest that distinct cells activity, including platelets, may be identified in different types of urticaria. PMID- 24236292 TI - Role of gap junctions and hemichannels in parasitic infections. AB - In vertebrates, connexins (Cxs) and pannexins (Panxs) are proteins that form gap junction channels and/or hemichannels located at cell-cell interfaces and cell surface, respectively. Similar channel types are formed by innexins in invertebrate cells. These channels serve as pathways for cellular communication that coordinate diverse physiologic processes. However, it is known that many acquired and inherited diseases deregulate Cx and/or Panx channels, condition that frequently worsens the pathological state of vertebrates. Recent evidences suggest that Cx and/or Panx hemichannels play a relevant role in bacterial and viral infections. Nonetheless, little is known about the role of Cx- and Panx based channels in parasitic infections of vertebrates. In this review, available data on changes in Cx and gap junction channel changes induced by parasitic infections are summarized. Additionally, we describe recent findings that suggest possible roles of hemichannels in parasitic infections. Finally, the possibility of new therapeutic designs based on hemichannel blokers is presented. PMID- 24236295 TI - Immunization with a neural-derived peptide protects the spinal cord from apoptosis after traumatic injury. AB - Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-alpha). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-alpha concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy. PMID- 24236296 TI - Practical guidance for implementing predictive biomarkers into early phase clinical studies. AB - The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study. PMID- 24236298 TI - A quantitative analysis of the impact on chromatin accessibility by histone modifications and binding of transcription factors in DNase I hypersensitive sites. AB - It is known that chromatin features such as histone modifications and the binding of transcription factors exert a significant impact on the "openness" of chromatin. In this study, we present a quantitative analysis of the genome-wide relationship between chromatin features and chromatin accessibility in DNase I hypersensitive sites. We found that these features show distinct preference to localize in open chromatin. In order to elucidate the exact impact, we derived quantitative models to directly predict the "openness" of chromatin using histone modification features and transcription factor binding features, respectively. We show that these two types of features are highly predictive for chromatin accessibility in a statistical viewpoint. Moreover, our results indicate that these features are highly redundant and only a small number of features are needed to achieve a very high predictive power. Our study provides new insights into the true biological phenomena and the combinatorial effects of chromatin features to differential DNase I hypersensitivity. PMID- 24236297 TI - Evaluating the importance of the carotid chemoreceptors in controlling breathing during exercise in man. AB - Only the carotid chemoreceptors stimulate breathing during hypoxia in Man. They are also ideally located to warn if the brain's oxygen supply falls, or if hypercapnia occurs. Since their discovery ~80 years ago stimulation, ablation, and recording experiments still leave 3 substantial difficulties in establishing how important the carotid chemoreceptors are in controlling breathing during exercise in Man: (i) they are in the wrong location to measure metabolic rate (but are ideally located to measure any mismatch), (ii) they receive no known signal during exercise linking them with metabolic rate and no overt mismatch signals occur and (iii) their denervation in Man fails to prevent breathing matching metabolic rate in exercise. New research is needed to enable recording from carotid chemoreceptors in Man to establish whether there is any factor that rises with metabolic rate and greatly increases carotid chemoreceptor activity during exercise. Available evidence so far in Man indicates that carotid chemoreceptors are either one of two mechanisms that explain breathing matching metabolic rate or have no importance. We still lack key experimental evidence to distinguish between these two possibilities. PMID- 24236299 TI - Establishing an Imaging Protocol for Detection of Vascularity within the Median Nerve Using Contrast-Enhanced Ultrasound. AB - This preclinical study was conducted to develop discrete sonographic instrumentation settings and also safe contrast dosing that would consistently demonstrate perineural vascularity along the median nerve. This set of imaging studies was conducted with a convenience cohort of young adult female monkeys (Macaca fascicularis). Sonographic equipment settings and dosing were refined throughout the imaging series to ensure consistent contrast-enhanced ultrasound imaging. A mechanical index of 0.13 was consistently used for imaging. Perineural vessels were imaged with a suspension solution of 0.04 mL Definity/0.96 mL saline introduced over 5 minutes for a total dose of 0.8 mL of contrast solution. Blinded studies of high and low dose contrast, along with saline injections, were correctly identified by two experienced sonographers. This preclinical study established adequate equipment settings and dosing that allowed for a valid demonstration of vascularity surrounding the median nerve. PMID- 24236300 TI - MicroRNA: A New Player for Cancer Chemoprevention. PMID- 24236301 TI - Cross-device automated prostate cancer localization with multiparametric MRI. AB - Prostate cancer localization using supervised classification techniques has aroused considerable interest in medical imaging community in recent years. However, it is crucial to have an accurate training data set for supervised classification techniques. Since different devices with, e.g., different protocols and/or field strengths cause different intensity profiles, each device/protocol must have an accompanying training data set, which is very costly to obtain. It is highly desirable to adapt the existing classifier(s) trained for one device/protocol to help classify data coming from another device/protocol. In this paper, we propose a novel method that has the ability to design classifiers obtained from one imaging protocol and/or MRI device to be used on a data set from another protocol and/or imaging device. As an example problem, we consider prostate cancer localization with multiparametric MRI. We show that simple normalization techniques such as z-score are not sufficient for cross-device automated cancer localization. On the other hand, the method we have originally developed based on relative intensity allows us to successfully use a classifier obtained from one device to be applied on a test patient imaged with another device. Proposed method also allows us to employ T2-weighted MR images directly instead of an additional step to normalize T2-weighted images usually performed in an ad hoc manner when T2 maps are not available. To demonstrate the effectiveness of the proposed method, we use a multiparametric MRI data set acquired from 18 biopsy-confirmed cancer patients with two separate scanners: 1) 1.5-T (Excite HD) GE and 2) 1.5-T (Achieva) Philips Healthcare scanners. A comprehensive visual, quantitative, and statistical analysis of the results show that methods we have developed allow us to: 1) perform cross-device automated classification and 2) use T2-weighted images without an ad hoc subject-specific normalization. PMID- 24236302 TI - Author's reply: To PMID 23070631. PMID- 24236303 TI - Author's reply: To PMID 23086804. PMID- 24236304 TI - Author's reply: To PMID 23531873. PMID- 24236305 TI - Author's reply: To PMID 21911318. PMID- 24236306 TI - Night shifts and breast cancer, occupational asthma. PMID- 24236307 TI - Author's reply: To PMID 23531869. PMID- 24236308 TI - Author's reply: To PMID 23531868. PMID- 24236309 TI - Author's reply: To PMID 23395706. PMID- 24236310 TI - Abstracts of the 62nd Annual Scientific Session of the American College of Cardiology. March 9-11, 2013. San Francisco, California, USA. PMID- 24236311 TI - Fieldwork: The great outdoors. PMID- 24236312 TI - Precautionary measures. PMID- 24236313 TI - Data deadline. PMID- 24236314 TI - Keep asking. PMID- 24236315 TI - Parasitic infections: Time to tackle cryptosporidiosis. PMID- 24236316 TI - Global change: Ecology must evolve. PMID- 24236317 TI - [Drugs of a Baroque monastery pharmacy]. AB - This paper deal with a manuscript from the years 1714-1720, originating most probably from the hospital of the Brothers of Mercy in Nove Mesto nad Metuji. it contains the records of the hospital pharmacy about the drugs prepared for both patients and monks who operated this hospital. The included drugs were mainly intended for elderly males. The manuscript lists about fifteen hundred drugs and more than three hundred active ingredients, of which about two thirds were of plant origin. The paper presents the compositions of more important drugs and partly deals also with their preparation. PMID- 24236319 TI - [Hand surgery. Dorsal capsulodesis in chronic SL instability]. PMID- 24236320 TI - [Hand surgery. Fractures of the dorsal finger base end member]. PMID- 24236321 TI - Surveillance snapshot: myomectomies and hysterectomies performed for uterine fibroids at military health facilities, active component service women, U.S. Armed Forces, 2000-2012. PMID- 24236322 TI - Surveillance snapshot: Births, active component service women, U.S. Armed Forces, 2001-2012. PMID- 24236324 TI - Telemedicine: winners and losers. PMID- 24236323 TI - The health of healthcare, Part II: patient healthcare has cancer. AB - In this article, we make the etiologic diagnosis for a sick patient named Healthcare: the cancer of greed. When we explore the two forms of this cancer- corporate and bureaucratic--we find the latter is the greater danger to We the Patients. The "treatments" applied to patient Healthcare by the Congressional "doctors" have consistently made the patient worse, not better. At the core of healthcare's woes is the government's diversion of money from healthcare services to healthcare bureaucracy. As this is the root cause, it is what we must address in order to cure, not sedate or palliate, patient Healthcare. PMID- 24236325 TI - [Comparative analysis of a new human cell line 4BL karyotype at long-term cultivation. Ploidy of chromosomal set]. AB - Long-term cultivation of human cells, including stem cells, can lead to substantial transformation of the karyotype and occurrence of genetic instability. The aim of this research was a comparative cytogenetic study of the karyotype of a new human stem cell line 4BL at 160 and 205 passages. The absence of 10 and 13 pairs of chromosomes and the monosomy of chromosomes 4, 8, 10, 11, 13, 15, 17, 21, X were observed; also six regular marker chromosomes were detected. Chromosomes 1, 15 and 21 are involved in translocations t(l;11), t(5;15), t(12; 15), t(16;21). Modal class of the karyotype is within 41-43 chromosomes at both 160 and 205 passages. The frequency of polyploid cells have been increased from 2.8% at 160 passage up to 36% at 205 passage. Cells with a near-haploid karyotype were not detected at 205 passage (in contrast to 24.6% at 160 passages) and a decline of the level of premature separation of chromatids was observed. We assume stabilization of karyotype of the cell line 4BL at 205 passage and consider that further research is needed to predict the direction of karyotypic evolution of these cells in vitro. PMID- 24236326 TI - Progress towards poliomyelitis eradication: Afghanistan, January 2012-August 2013. PMID- 24236327 TI - Estimating meningitis hospitalization rates for sentinel hospitals conducting surveillance of invasive bacterial vaccine preventable diseases. PMID- 24236328 TI - Drug approvals voluntarily withdrawn. PMID- 24236329 TI - Cattle drug's sales suspended after lameness reports. PMID- 24236331 TI - Bighorn sheep may be at risk for TSEs. PMID- 24236330 TI - Investigation follows dog illnesses, deaths in Ohio. PMID- 24236332 TI - Meeting of the WHO expert working group on surveillance of influenza antiviral susceptibility, Geneva, July 2013. PMID- 24236333 TI - Global routine vaccination coverage, 2012. PMID- 24236334 TI - WHO advisory committee on immunization and vaccine related implementation research (IVIR, formerly QUIVER): executive summary report of 7th meeting. PMID- 24236335 TI - Social conflict in Latin America sparked by inequality, says new UNDP report. PMID- 24236336 TI - Medical devices; ophthalmic devices; classification of the scleral plug. Final rule. AB - The Food and Drug Administration (FDA or Agency) is classifying the scleral plug into class II (special controls), and exempting the scleral plugs composed of surgical grade stainless steel (with or without coating in gold, silver, or titanium) from premarket notification (510(k)) and continuing to require premarket notification (510(k)) for all other scleral plugs in order to provide a reasonable assurance of safety and effectiveness of the device. The scleral plug is a prescription device used to provide temporary closure of a scleral incision during an ophthalmic surgical procedure. PMID- 24236337 TI - Schedules of controlled substances: temporary placement of three synthetic phenethylamines into Schedule I. Final order. AB - The Deputy Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily schedule three synthetic phenethylamines into the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). The substances are 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2 methoxybenzyl)ethanamine (25I-NBOMe; 2C-I-NBOMe; 25I; Cimbi-5), 2-(4-chloro-2,5 dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25C-NBOMe; 2C-C-NBOMe; 25C; Cimbi 82), and 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B NBOMe; 2C-B-NBOMe; 25B; Cimbi-36) [hereinafter 25I-NBOMe, 25C-NBOMe, and 25B NBOMe]. This action is based on a finding by the Deputy Administrator that the placement of these synthetic phenethylamines and their optical, positional, and geometric isomers, salts and salts of isomers in schedule I of the CSA is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, dispense, import, export, engage in research, conduct instructional activities, and possess), or propose to handle these synthetic phenethylamines. PMID- 24236338 TI - Recent Advances in the Surgery and Adjuvant Treatment of Lung Cancer: Tribute to Robert J. Ginsberg. PMID- 24236339 TI - [Planar cell polarity in polycystic kidney disease]. PMID- 24236340 TI - [Kidney volume and renal function in ADPKD]. PMID- 24236341 TI - [ADPKD and hypertension: recent evidence]. PMID- 24236342 TI - [Liver cysts: influence of liver cysts on the quality of life and the treatment for liver cysts]. PMID- 24236343 TI - [Management of cysts infection in ADPKD]. PMID- 24236344 TI - [Transcatheter arterial embolization (TAE) therapy on a patient with polycystic kidney disease]. PMID- 24236345 TI - [Early diagnosis in ADPKD: toward early treatment]. PMID- 24236346 TI - [Basic research and clinical aspect in ARPDK: new insight]. PMID- 24236347 TI - [Mechanism of cystic bile duct dilatation in relation to biliary infection]. PMID- 24236348 TI - [A case of nephrotic syndrome and rapidly progressive glomerulonephritis associated with MSSA infection]. PMID- 24236349 TI - [A case of anti-GBM glomerulonephritis and membranous nephropathy in a patient with primary biliary cirrhosis]. PMID- 24236350 TI - [A case of anti-neutrophil cytoplasmic antibody (ANCA)-negative necrotizing glomerulonephritis (GN) superimposed on mixed connective tissue disease (MCTD)]. PMID- 24236351 TI - Perspectives. PMID- 24236352 TI - A special issue in memory of Andrew Szczeklik. PMID- 24236353 TI - Cognitive regulatory control therapies. AB - Cognitive regulatory control processes play an essential but typically unappreciated role in maintaining mental health. The purpose of the current paper is to identify this role and demonstrate how cognitive-behavioral and related techniques can compensate for impairments. Impaired cognitive regulation contributes to the overly intense emotional states present in anxiety disorders, depression, and personality disorders; progression of adaptive hypomania to mania; expression of psychosis in the conscious and awake state; dominance of immature defense mechanisms in borderline and other personality disorders. A wide variety of standard (monitoring, reappraisal, response inhibition, relaxation training) and more novel (suppression therapy, willful detachment, cost-benefit analysis, normalization, mature defense mechanism training) cognitive-behavioral and related techniques can be applied to compensate for cognitive regulatory control impairments, and their success probably aligns with this capacity. PMID- 24236355 TI - Process and technique factors associated with patient ratings of session safety during psychodynamic psychotherapy. AB - This study investigates the relationships between patient ratings of in-session safety with psychotherapeutic techniques and process. Ninety-four participants received Short-Term Dynamic Psychotherapy (STDP) at a university-based clinic. Patient experiences of therapeutic process were self-assessed early in treatment using the Session Evaluation Questionnaire (SEQ Stiles, 1980). Techniques implemented in session were identified using the Comparative Psychotherapy Process Scale (CPPS: Hilsenroth et al., 2005). Alliance was evaluated with the Combined Alliance Short Form-Patient Version (CASF-P; Hatcher and Barends, 1996). Safety significantly correlated with session depth, smoothness, and positivity. Safety was significantly related to the interaction of psychodynamic interpersonal and cognitive-behavioral techniques, but to neither individual subscale Safety significantly correlated with CASF-P Total, Confident Collaboration, and Bond. Patient experiences of safety are consistent with exploration and depth of session content. Integration of some CB techniques within a psychodynamic model may facilitate a sense of safety. Safety is notably intertwined with the therapeutic relationship. PMID- 24236354 TI - Pragmatic psychodynamic psychotherapy for a patient with depression and breast cancer: functional MRI evaluation of treatment effects. AB - Time-limited psychodynamic psychotherapy is garnering empirical support as an intervention for clinical depression. However, research is needed to examine the efficacy of psychodynamic approaches among patients presenting with diverse psychiatric and medical problems. This case study examined the efficacy of eight sessions of pragmatic psychodynamic psychotherapy (PPP) in treating a woman with major depression and breast cancer. Pre- to posttreatment assessment indicated significant reductions in depression and weekly assessment indicated increased environmental reward was associated with reduced depression. Secondary aims involved piloting a functional magnetic resonance imaging (fMRI) task as a neurobiological indicator of depression attenuation as a function of PPP. This assessment was conducted to explore alternative means of evaluating treatment responsiveness and addressing the problem of arbitrary metrics in measuring change. Clinical and assessment implications are discussed, with a focus on innovative approaches to evaluate treatment outcome and behavioral and neurobiological mechanisms of change associated with PPP. PMID- 24236356 TI - Psychotherapeutic implications of self disorders in schizophrenia. AB - The ways terms are defined have a significant impact on psychotherapeutic theory, research, and practice. This paper will provide the definitions of and conceptual distinctions among terms that have emerged from embodied and embedded approaches to the self and its disorders. First, it will offer the distinctions regarding conceptual definitions of disembodiment and hyperreflexivity to differentiate these from other psychopathological configurations and normal conditions. Second, it will present disturbances of the self that arise in the consensual processes of establishing intersubjectivity and manifest themselves in narratives. Third, the paper will present the principles of possible psychotherapeutic interventions for persons with schizophrenia. The conclusion states that both ontological (structural) as well as ontogenetic (autobiographical) aspects should be considered in the hermeneutic process of understanding patients. Content should be a significant element of this latter analysis. PMID- 24236357 TI - Containing psychotic patients with fragile boundaries: a single-session group case study. AB - This case study describes a single group psychotherapy session of six individuals suffering from schizophrenia or schizoaffective illness, which was characterized by numerous manifestations of fragile Ego boundaries. Based on these illustrations of fragile Ego boundaries, we explore some of the group's core therapeutic actions against psychosis. We discuss how the group (1) provides access to a structuring auxiliary Ego, (2) acts as a containing object by establishing firm boundaries and by mentalizing patients' psychotic productions, and (3) may become a solid object representation introjected by individuals wrestling with porous Ego boundaries and a poor sense of self. We conclude that, in addition to the known role of group therapy in increasing mature defenses, developing insight and providing social support, the group promotes healthier Ego boundaries, and eventually improves self-differentiation, and also tolerance to interpersonal proximity. This case study clarifies group therapy dynamics with individuals suffering from psychosis. PMID- 24236358 TI - What have we learnt about war? PMID- 24236359 TI - Economic sanctions and child health. PMID- 24236360 TI - IPPNW in Hiroshima: a call to end 'the curse of nuclear fission'. PMID- 24236361 TI - The psychic malignancy of the Afghan War. PMID- 24236362 TI - The biomedicalisation of war and military remains: US nuclear worker compensation in the 'post-Cold War'. AB - This paper analyses the recent legislation and administration of United States nuclear worker compensation--the Energy Employees Occupational Illness Compensation Programme Act (EEOICPA)--in order to show the domestic impacts of war and the social order that has been established to respond to the Cold War legacy of occupational exposures, illness, and death. Examining the epistemological politics and material effects of compensation, an insufficiently analysed aspect of the Cold War, I argue that the system designed to redress the occupational exposures of nuclear workers accomplishes something else: obscuring the ethical problem of misinformation and missing data from the Cold War era; mobilising an industry of knowledge and market-economic opportunities in the arena of biomedical exposure assessment and dose reconstruction for parts of the former US nuclear complex; and, lastly, dematerialising and depoliticising geographies of the Cold War and its differential impacts through an individualistic epidemiological reprocessing of radiation exposures. The paper shows how the general claims procedure, combined with two methods mandated by EEOICPA--dose reconstruction and the probability of causation--effectively de link workers from each other, and worksites from homes, pin compensation to a cost-benefit logic, implicate genuine scientific complexity and uncertainty in an ongoing denial of the toxic legacies of war, and ethically undermine the social justice aims of the legislation. The article ends by considering some of the ways that US nuclear workers have responded to living as the remains of both US bomb production and the compensation system. PMID- 24236363 TI - Someone to watch over me: exposure to war events and trust in the armed forces in Israel as factors in war-related stress. AB - This study examined the role of trust in the national armed and security forces in Israel as a potential protective factor in post-war stress symptoms, alongside other known correlates such as exposure to war events, sense of danger, and demographics. A cluster sample of 870 residents of the town of Kiryat-Shemona in Israel participated in this correlational study. The town was under heavy bombing during the second Lebanon war, and data collection took place about a year after the end of the war. Our results suggest that while sense of danger and exposure to war events are the strongest correlates of stress related symptoms, trust in the armed forces was negatively correlated with stress, even after controlling for demographics; therefore supporting our hypothesis. Theoretical, methodological and practical implications are discussed in light of our findings. PMID- 24236364 TI - Time trends in MB-PB ratio among untreated leprosy patients attending a referral hospital in UP, India during 2001 to 2010. AB - Secular trends in incidence of leprosy serve as a powerful tool in determining progress in reaching eradication. However, the interpretation of these trends must take into account both operational and epidemiological factors. A study was done to assess a time trend in the ratios of MB & PB from 2001 to 2010 based on the leprosy patients registered in a referral hospital in UP, India. Data were analyzed based on the gender, age and residence. Regardless of these factors, MB proportion shows no significant trends. These findings are discussed and it is concluded that we are no more close to eradication as compared to the status over a decade ago. Hence, much greater efforts will be required to promote early detections of MB cases, whether children or adults, male or female. PMID- 24236365 TI - Mycobacterium tuberculosis: approach to development of improved strategies for disease control through vaccination and immunodiagnosis. AB - Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. Estimates till date ascertain the fact that Tuberculosis (TB) is continuing to be the leading cause of death worldwide. The infection from single infectious agent Mycobacterium tuberculosis is killing about 3 million individuals every year and accounts for around 18.5% of all deaths in adults between the age group of 15 and 65. An average of 1.79 billion people, which constitutes roughly one-third of the world's population, is infected with the causative agent M. tuberculosis and is at risk of developing the disease. This situation highlights the relative shortcomings of the current treatment and diagnosis strategies for TB and the limited effectiveness of public health systems, particularly in resource-poor countries where the main TB burden lies. The timely identification of persons infected with Mycobacterium tuberculosis and rapid laboratory confirmation of tuberculosis are two key factors for the treatment and prevention of the disease. Novel molecular assays for diagnosis and drug susceptibility testing offer several potential advantages over the above methods including faster turnaround times, very sensitive and specific detection of nucleic acids, and minimal, or possibly no, prior culture. The need for new technologies for rapid diagnosis of tuberculosis is clear. Most studies of mycobacterial immunity attributes focus on proliferation of T cells, production of cytokines and cytolytic activity. A proper vaccine for tuberculosis can be developed by using a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. Development of new vaccines against TB should include some important aspects learned from BCG use such as mucosal routes of immunization; revaccination of BCG immunized subjects, booster immunization and prime-boost strategy with wild-type BCG, and other vaccine candidates. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. PMID- 24236366 TI - Multiple nerve abscesses on cutaneous radial nerve--a case of pure neural leprosy. AB - Leprosy is a unique infectious disease due to varied spectrum of clinical signs it exhibits. Pure neural leprosy (PNL) is an unusual form of leprosy and accounts for 4-8% of all leprosy cases. It can manifest as a simple tingling sensation to complex and tragic motor paralysis. Here we report a case of PNL involving isolated cutaneous radial nerve as multiple abscesses along the course of the nerve. To the best of our knowledge, this is rarest presentation of pure neural leprosy. PMID- 24236368 TI - Vulnerability, risk, and qualitative methodologies. PMID- 24236367 TI - Non pitting edema, arthritis and ichthyosis; presenting manifestation of leprosy. AB - Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. Predominantly involving skin and nerves and having classic clinical description, the diagnosis may be clear-cut in majority of patients but may be challenging in others. Non-pitting edema, ichthyosis and arthritis are uncommon in leprosy and very rare in tuberculoid type where the diagnosis may be challenging unlike relatively clear-cut clinical picture in lepromatous type. Musculoskeletal manifestation is seen in 1-5% of cases and usually associated with reactional states where again the diagnosis sometimes becomes evident. High index of suspicion is therefore recommended in patients with unexplained systemic illness especially in endemic areas. Herein we report a young male with non pitting edema and symmetric peripheral arthritis involving all four limbs, and ichthyosis as presenting manifestation of borderline leprosy where the neuro-cutaneous manifestation developed two months after the said presenting features and in absence of a reactional state. PMID- 24236369 TI - Health inequities experienced by Aboriginal children with respiratory conditions and their parents. AB - Asthma and allergies are common conditions among Aboriginal children and adolescents. The purpose of this study was to assess the health and health-care inequities experienced by affected children and by their parents. Aboriginal research assistants conducted individual interviews with 46 Aboriginal children and adolescents who had asthma and/or allergies (26 First Nations, 19 Metis, 1 Inuit) and 51 parents or guardians of these children and adolescents. Followup group interviews were conducted with 16 adolescents and 25 parents/ guardians. Participants reported inadequate educational resources, environmental vulnerability, social and cultural pressures, exclusion, isolation, stigma, blame, and major support deficits. They also described barriers to health-service access, inadequate health care, disrespectful treatment and discrimination by health-care providers, and deficient health insurance. These children, adolescents, and parents recommended the establishment of culturally appropriate support and education programs delivered by Aboriginal peers and health professionals. PMID- 24236370 TI - Infant-feeding among low-income women: the social context that shapes their perspectives and experiences. AB - This article explores the perspectives of low-income women in order to better understand the social context that shapes their infant-feeding perspectives and experiences. The authors used purposive sampling to conduct 3 focus groups with 19 women who were formula-feeding their infants in 1 urban and 2 rural communities in the eastern region of the island of Newfoundland in Canada. Elements of the social context for infant-feeding included the prevalence of myths and misinformation about breastfeeding; cultural expectations about infant behaviour; the postnatal experience, including the medicalization of birth and breastfeeding; partner support and child-care workload; cultural stigma of breastfeeding; and a moralizing ideology that equates breastfeeding with "good mothering. "The authors discuss the implications of the findings from a nursing and public health perspective, offering 7 recommendations for how nurses and health professionals might better support women and their families. PMID- 24236371 TI - Decolonizing sexual health nursing with Aboriginal women. AB - Nurses striving to provide quality health care for and with Indigenous individuals and communities in Australia face particular challenges. Past and present discriminatory or non-responsive health-care practices and policies have caused many Aboriginal women and their families to mistrust health-care professionals and practices. It is vital that nurses develop culturally safe and respectful ways of working in partnership with Aboriginal colleagues and clients. The author discusses how nurses in both Canada and Australia have drawn on critical and postcolonial feminist theories, Indigenous epistemologies and methodologies, and models of cultural safety to develop a more responsive, decolonizing approach to health care and training. Two practice examples from the Australian context highlight both the challenges and the benefits of incorporating decolonizing approaches into practice. The similarities in and differences between situations reveal a clear need for responsive and flexible decolonizing approaches. PMID- 24236372 TI - Impact of the global economic crisis on the health of unemployed autoworkers. AB - A phenomenological investigation was undertaken to examine the effects of the 2008-09 global economic recession on the health of unemployed blue-collar autoworkers in the Canadian province of Ontario between September and November 2009. A total of 22 men and 12 women took part. Participants completed a quantitative demographic and financial questionnaire. The qualitative aspect of the study consisted of a phenomenological component comprising semi-structured focus group sessions lasting 2 to 2.5 hours. The number of years employed ranged from 2 to 31.7 with a mean of 15 +/- 8. Participants reported high levels of stress, anxiety, and depression; increased physical pain and discomfort; changes in weight and sexual function; and financial hardships, including inability to purchase prescribed medications. The authors conclude that unemployment associated with the global recession has negative health effects on autoworkers in Ontario. PMID- 24236373 TI - Conducting research with criminalized women in an incarcerated setting: the researcher's perspective. AB - Although women incarcerated by the criminal justice system encounter significant challenges to their health, there has been little research focusing on their health practices. To contribute to the research literature on the health experiences of criminalized women, the authors conducted a multi-method study as part of a program of research exploring the health promotion and health-literacy skills of women in conflict with the law. Conducting research in an incarcerated setting posed unique challenges and ethical dilemmas that problematized each phase of data collection. The authors share their experiences as health researchers conducting research in an incarcerated setting and with criminalized women. They document some of the challenges, successes, and valuable lessons learned during the research process in the hope that by sharing their knowledge with other health researchers they will support future studies with criminalized women. PMID- 24236374 TI - Evaluating nurses' use of HOBIC in home care. AB - Health Outcomes for Better Information and Care (HOBIC), a program funded by the Ontario Ministry of Health and Long-Term Care, introduces a collection of evidence-based clinical outcome measures reflective of nursing care. The authors report on an evaluation of the experiences of nurse early adopters of HOBIC in home care. The findings reveal challenges and nuances associated with the introduction of HOBIC and the use of supporting technologies in the delivery of home nursing care. Future implementation efforts should focus on optimizing the usability of technology and the usefulness of HOBIC in nursing practice. In addition, efforts need to be directed at supporting the full integration and use of HOBIC outcome data by nurses and management personnel to inform practice directions. PMID- 24236375 TI - Smoking prevention among youth: a multipronged approach involving parents, schools, and society. AB - The purpose of this research was to examine the perspectives of professionals on youth smoking prevention. The researchers used a qualitative descriptive design with a purposive sample of 9 professionals consisting of elementary school teachers, public health nurses, and tobacco control experts from non-governmental organizations. Data were collected through semi-structured interviews and were analyzed for themes. The view of the participants was that although parents have the main responsibility for educating their children about smoking, a multipronged approach, which also includes school and society more generally, will have the greatest effect. The need for a comprehensive, multifaceted, multichannel approach might explain why single smoking prevention interventions are often ineffective. Public health nurses are in a prime position to foster and support parents' smoking prevention interventions with their children and to advocate for strong tobacco control social policy and best practice for smoking prevention curricula in schools. PMID- 24236376 TI - Nurses' intention to support informed decision-making about breast cancer screening with mammography: a survey. AB - There is growing interest in informed decision-making about breast cancer screening with mammography and growing advocacy for the provision of balanced information about potential benefits and harms. The authors report on a survey evaluating nurses' intention to support women targeted by the Quebec Breast Cancer Screening Program in making informed decisions about breast cancer screening with mammography. Of the 840 questionnaires completed, 618 were included in the data analysis. The mean +/- standard deviation score for intention was 1.7 +/- 1.2 on a 6-point Likert scale ranging from -3 to +3, indicating strong intention to support the targeted women. Perceived behavioural control was the theory-based variable most strongly associated with intention, followed by attitude and social norm. These results can be used to develop interventions to train nurses in integrating informed decision-making about breast cancer screening with mammography into their practice and to design relevant decision support tools. PMID- 24236377 TI - Self-efficacy in romantic relationships: prediction of relationship attitudes and outcomes. AB - Three studies examine discriminant and predictive validity of a self-report measure of self -efficacy in romantic relationships (Self-Efficacy in Romantic Relationships; SERR). Study 1 indicates SERR scores predict relationship anxiety and expectations of relationship success when general self-efficacy, self-esteem, social desirability, and efficacy beliefs about relating to specific relationship partners are considered. Study 2 indicates SERR scores predict later relationship satisfaction and commitment when relationship type and length are considered. Study 3 indicates that SERR scores predict later relationship outcomes when other self-efficacy indicators are considered. The SERR assesses broad feelings of relationship self-efficacy, independent of specific relationships or partners. PMID- 24236378 TI - Distinguishing source of autonomy support in relation to workers' motivation and self-efficacy. AB - The purpose was to investigate the relationship between autonomy support by managers and co-workers and employees' work motivation and self-efficacy in two studies. In Study 1, a sample of 343 Swedish workers completed surveys, and in Study 2, we followed up with a subsample of 98 workers one year later. As in previous studies, managers support of autonomy was significantly positively related to workers' outcomes. However, the results of Study 1 also showed that co worker autonomy support was related to these outcomes over and above the effects of manager support. Study 2 showed that changes in autonomy support from co workers during one year significantly predicted motivation and self-efficacy one year later, while change in support from managers was unrelated to outcomes later. These findings provide evidence for the importance of both vertical and horizontal sources of support. PMID- 24236379 TI - The emotional and attitudinal consequences of religious hypocrisy: experimental evidence using a cognitive dissonance paradigm. AB - We explored the emotional and attitudinal consequences of personal attitude behavior discrepancies using a religious version of the hypocrisy paradigm. We induced cognitive dissonance in participants (n = 206) by making them feel hypocritical for advocating certain religious behaviors that they had not recently engaged in to their own satisfaction. In Experiment 1, this resulted in higher levels of self-reported guilt and shame compared to the control condition. Experiment 2 further showed that a religious self-affirmation task eliminated the guilt and shame. In Experiment 3, participants boosted their religious attitudes as a result of dissonance, and both religious and non-religious self-affirmation tasks eliminated this effect. The findings provide evidence that dissonance induced through religious hypocrisy can result in guilt and shame as well as an attitude bolstering effect, as opposed to the attitude reconciliation effect that is prevalent in previous dissonance research. PMID- 24236380 TI - Stereotype threat and lift effects in motor task performance: the mediating role of somatic and cognitive anxiety. AB - The aim of this investigation was to replicate the stereotype threat and lift effects in a motor task in a neutral sex-typed activity, using somatic and cognitive anxiety as key mediators of these phenomena. It was hypothesized that an ingroup/outgroup social categorization based on gender would have distinctive effects for female and male participants. A total of 161 French physical education students were randomly assigned to three threat conditions--no threat, female threat, and male threat--thus leading to a 3 x 2 (threat by gender) design. The analyses revealed a stereotype lift effect on the performances for both male and female participants, as well as a stereotype threat effect only for female participants. They also indicated that somatic anxiety had a mediating effect on the performance of female participants targeted by a negative stereotype, but that it had a facilitating effect on their performance. The stereotype threat and lift effects on motor tasks were replicated in a neutral sex-typed activity and somatic anxiety seems to have a facilitating mediating effect of the relationships between the gender-conditions (control or female threat) interaction and free-throw performance. The model used to distinguish somatic and cognitive anxiety appeared to be a relevant means of explaining the stereotype threat and lift mechanisms. PMID- 24236381 TI - The power of change: interpersonal attraction as a function of attitude similarity and attitude alignment. AB - Does attitude alignment predict attraction? Would you like a stranger more who shifts her/his attitudes to more closely align with yours? In pairs, participants (N = 77) discussed social issues about which they disagreed and received false feedback on whether the partner engaged in attitude alignment (shifted her/his attitudes toward the participant's attitude) following discussion. Participants also received false feedback about the proportion of similarity to the partner on a set of issues (i.e., 25%, 50%, or 75%). Participants reported greater attraction to partners who engaged in attitude alignment and who were more similar. Moreover, similarity and attitude alignment interacted. Similarity predicted attraction when attitude alignment did not occur, but did not predict attraction when attitude alignment did occur. Finally, partner attitude alignment led to participant attitude alignment, and perceived reasoning ability mediated the attitude alignment-attraction relationship. PMID- 24236383 TI - Happy summer! PMID- 24236382 TI - Testing the BIAS map model: the positive effects of perceiving weakness and harmony in powerful out-groups. AB - Two experimental studies were used to test predictions derived from the BIAS map model. While the first experiment manipulated the perception of power in the out group (the USA), the second manipulated the perceived harmony of the relationships between this out-group and the participants' own national group. The results confirmed the hypotheses derived from the model. The manipulation of power affected the perception of competence, thus affecting emotions and behavioral dispositions towards out-group members. The manipulation of perceived harmony of intergroup interests had a similar effect, but was not mediated by changes in the attribution of competence, but of warmth. Attitudes did not play a significant role in the prediction of emotions and behavioral intentions. PMID- 24236384 TI - Oral and maxillofacial pathology case of the month. Erythema migrans (ectopic migratory glossitis/ectopic geographic tongue). PMID- 24236386 TI - From poster child to good health. PMID- 24236385 TI - Be smart and be aware. PMID- 24236387 TI - Time is a gift. PMID- 24236388 TI - My experience with oral cancer. PMID- 24236389 TI - Oral health care in cancer patients: you can make a difference! AB - Dentists are in a unique position to care for cancer patients before, during and after treatment. This paper outlines foundational knowledge highlighting the dentist's role in the management of patients treated with chemotherapy for various types of cancer as well as those who receive radiation therapy for cancer of the head and neck. The value of the dentist in a multidisciplinary team approach to cancer care is stressed along with specific treatment modalities to improve patient comfort and quality of life. PMID- 24236390 TI - Living in limbo: Ethics and experience in a conversation about persistent oral lesions. AB - This case report presents a conversation that the authors had with a patient who is suffering from oral lichen planus and oral cancer. The reason that the authors approached the patient for an interview was to find out why he decided to enroll in an experimental study related to his oral cancer. The patient reported that it was "the waiting" that led him to enroll in this study--that is, the pressure of waiting for oral cancer to reemerge was simply unbearable, and enrolling in this experimental study enabled him to take a more proactive approach to his illness. The authors view this "waiting" as a "limbo experience" and reflect on the implications of this limbo experience for dental ethics and research ethics. PMID- 24236391 TI - CAT of the month. Risk of developing alveolar osteitis post-operatively following dental extraction is positively correlated to smoking (UT CAT #2470). PMID- 24236392 TI - Value for your profession. Building a strong online presence--any why it's so important. PMID- 24236393 TI - [Strange circumstances...]. PMID- 24236394 TI - [Home care: tact and tactics]. AB - This article deals with home care for people suffering from mental disorders or cognitive impairments. When caregivers look after these patients, they have to reconcile different requirements, which can sometimes be in tension with each other: winning and retaining the confidence of patients who do not always easily accept help; facilitating their autonomy or limiting their loss of autonomy; protecting them, ensuring their safety while acting in their best interests. Combining these different goals, entails encouraging them in what they want to achieve whilst intervening when they endanger themselves. As a result caregivers need tact and diplomatic skills. But these are insufficient when it is necessary to protect the patient against their will. In particular when they are living in their own home they are far less constrained by social norms and so practical compromises become necessary. In discussing these practises, the article explores the notion of "ruse" which we consider as both a form of practical problem solving and as a deception. After introducing several forms of "trick" used in caring, the article considers whether such practices are compatible with care ethics. PMID- 24236395 TI - [Caring: searching for consensus or principle of necessary conflict?]. AB - By dint of habits, the demand of consensus substitute the poison for the remedy. The consensus sounds the death knell for the ethics. Pursuing (striving towards) the unity, the consensus demonizes the conflict and seek explicitly a way to eliminate it regarding its visible chaos. A contrario, dissensus assures, by the fertile link of speech, the ethic blow of the "living-together" concept. Thereby, a "double-je" appears, able to say "Here I am" to the other, whoever it is, looming or vulnerable. Dissensus signs the emancipation, the unfold of the subject and point at surpassing oneself. The displaying process goes through an ipseity reasoning which emerges from otherness, free itself from the latter, to finally return to it in terms of solicitude: to live with, against and for the other. This work tries to show the dissensus as a sound and required conflict, which guarantees an opening ethics, a path of excellence for the one who are concerned by the best thing a human being can offer: caring. PMID- 24236396 TI - [Encountering the subject in the health field: a human care theory based on lived experience]. AB - Dominated by a bio-mechanistic paradigm, Western health systems are suffering from numerous problems. One such problem is the lack of consideration for lived experiences and the complexity and depth of meaning that characterize them. We accordingly emphasize in this text the importance of talking a deep look at the experiences of the cared-for Subject and changing the viewpoint on his or her problems. We defend this viewpoint with the help of a few ideas borrowed from Georges Canguilhem. We then refer to a socio-phenomenological approach inspired by the work of Alfred Schutz which allows us to better grasp people's lived experiences. We thus rehabilitate the Subject by proposing a human care theory that focuses on its' relationship(s) with the body, others, time and space, as well as on self-referent identity labels that give meaning to one's existence. This study is a theoretical reflection on human care that considers professional collaboration and interdisciplinarity, and that does not ignore the concrete practices of stakeholders and professionals. PMID- 24236397 TI - [The links between research and practice: knowledge transfer, the use of evidence based data and the renewal of practices]. AB - Nurses in clinical settings still do not fully rely on scientific knowledge to guide their practices and only rarely resort to the literature to find answers to their questions or clinical concerns. The sustainable implementation of projects that use knowledge founded on scientific evidence presents an important challenge that nursing research must address. The goal of this article is to present a strategy adopted by the Reseau infirmier et partenaires de soins (RI-PS) of the Universite de Montreal (Quebec). The strategy's aim is to promote the optimal and perennial use of scientific knowledge in clinical settings and to incorporate the use of best practices based on scientific evidence to their operating procedure. First, we will present a brief overview of the evolution of nursing research and its impacts, followed by an inventory of the success factors of the use of scientific knowledge in practical settings, and finally the presentation of a model, Implementation Science, on which the RI-PS strategy relies for its projects. We also outline the network and one of its developments, the knowledge transfer portal and healthcare partners (PES). PMID- 24236398 TI - [What a tracheostomy changes in a child with a neuromuscular disease]. AB - INTRODUCTION: The severe course of certain early onset neuromuscular disorders may lead to the indication of a tracheostomy for a child, a step that parents dread. Previous publications report that families in this situation face particular difficulties and need to develop new strategies of organization and adaptation in order to cope with the new context of life. OBJECTIVES: The aim of this study is identifying, through the mother's eye, what changes implies tracheostomy for the child and his family. METHOD: A qualitative study using semi strutured interviews was performed to the mothers of tracheostomized children affected with a severe neuromuscular disorder. RESULTS: The study revealed four main consequences: tracheostomy immediatly led to a feeling of security for the mother; the need of ventilation during the day increased the quotidian difficulties, in particular concerning social activities; tracheostomy enhanced social stigmatization; finally, tracheostomy requires that parents are specifically trained to be able to perform high level of paramedical care, what leads to a lack of autonomy and the complexity of burden for caregivers. CONCLUSION: Whenever respiratory insufficiency becomes very severe and there is not ventilatory autonomy, tracheostomy, synonimous of life, has as main inconvenient the need of handling different machines, what becomes a significant difficulty in the daily life. In the transition before/ after the tracheotomy, the nurse plays a key role in the evolution of the health care function of parents. PMID- 24236399 TI - [Parent's social representations of preschool childrens' weight and lifestyle]. AB - BACKGROUND: For preschool children aged four-five years, parents play a key role in the adoption of a healthy lifestyle. Social representations is central to understanding the choice of health behaviours promoted by the parent in their child's life. OBJECTIVE: To describe the social representations of parents with respect to the weight and lifestyle of children aged four to five. METHODS: In their descriptive qualitative study, two semi-structured interviews were conducted with a purposive sample of 14 parents who had either normal weight or (overweight or obese) children aged four to five until data saturation was achieved. The collected data was analyzed using inductive analysis. RESULTS: Some parents view weight as a health issue while others consider a chubby appearance as normal for child aged four to five. All participating parents view lifestyle as a demanding challenge. CONCLUSION: The results provide guidance for developing healthy lifestyle strategies that are consistent with parental obligations. PMID- 24236400 TI - [Research and training in midwifery by means of an interactive delivery simulator]. AB - This article is a reflective starting point within the framework of research on interactive delivery simulators. The objective is to open the perspective within our field to a set of concepts that allow us to create a base of reflection toward the goal of developing a theoretical framework with which to analyse and conceptualize activities with a delivery Simulator. The simulator SIMone is proposed as a means of analysis through general economic and philosophic approaches, by connecting simulation, teaching, the notion of instrument and technique. PMID- 24236401 TI - [Contributions and difficulties of experienced nursing participating in a journal club: a qualitative research analysis]. AB - INTRODUCTION: This article presents the impact of a journal club on expert nurses working in a hospital. AIM: This study describes the input of a journal club and the difficulties encountered by experienced nurses in pain management and palliative care. METHOD: Seven nurses participated in a written survey containing two questions about contributions and difficulties pertaining to their participation to a journal clubs. A qualitative inductive content analysis was used to organize and condense the collected data. FINDINGS: 127 meaning units were identified. The contributions were grouped in six categories: knowledge, discussion, professional assertiveness, reflection, theory-practice link and positive impulse. The difficulties were grouped in three categories: missing scientific knowledge, emotional impact and organization. Trusting and respectful interaction with peers promoted the integration of scientific knowledge. The results suggest that journal clubs' have an impact on nurses' professional assertiveness and are incentive to read scientific articles. CONCLUSION: Journal clubs are an interesting mean to initiate experienced nurses to read and critically appraise scientific articles. PMID- 24236402 TI - Nanoscale damping characteristics of boron nitride nanotubes and carbon nanotubes reinforced polymer composites. AB - This study compares the damping behavior of boron nitride nanotubes (BNNTs) and carbon nanotubes (CNTs) as reinforcement in PLC, a biodegradable copolymer. The damping behavior of PLC composites reinforced with 2 wt % or 5 wt % nanotube filler is evaluated by nanodynamic mechanical analysis (NanoDMA). The addition of 2 wt % CNT leads to the greatest enhancement in damping (tan delta) behavior. This is attributed to pullout in CNTs because of lower interfacial shear strength with the polymer matrix and a more effective sword-in-sheath mechanism as opposed to BNNTs which have bamboo-like nodes. BNNTs however have a superior distribution in the PLC polymer matrix enabling higher contents of BNNT to further enhance the damping behavior. This is in contrast with CNTs which agglomerate at higher concentrations, thus preventing further improvement at higher concentrations. It is observed that for different compositions, tan delta values show no significant changes over varying dynamic loads or prolonged cycles. This shows the ability of nanotube mechanisms to function at varying strain rates and to survive long cycles. PMID- 24236403 TI - Type-II histone deacetylases: elusive plant nuclear signal transducers. AB - Since the beginning of the 21st century, numerous studies have concluded that the plant cell nucleus is one of the cellular compartments that define the specificity of the cellular response to an external stimulus or to a specific developmental stage. To that purpose, the nucleus contains all the enzymatic machinery required to carry out a wide variety of nuclear protein post translational modifications (PTMs), which play an important role in signal transduction pathways leading to the modulation of specific sets of genes. PTMs include protein (de)acetylation which is controlled by the antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Regarding protein deacetylation, plants are of particular interest: in addition to the RPD3-HDA1 and Sir2 HDAC families that they share with other eukaryotic organisms, plants have developed a specific family called type-II HDACs (HD2s). Interestingly, these HD2s are well conserved in plants and control fundamental biological processes such as seed germination, flowering or the response to pathogens. The aim of this review was to summarize current knowledge regarding this fascinating, but still poorly understood nuclear protein family. PMID- 24236404 TI - Regulation of natural competence by the orphan two-component system sensor kinase ChiS involves a non-canonical transmembrane regulator in Vibrio cholerae. AB - In Vibrio cholerae, 41 chitin-inducible genes, including the genes involved in natural competence for DNA uptake, are governed by the orphan two-component system (TCS) sensor kinase ChiS. However, the mechanism by which ChiS controls the expression of these genes is currently unknown. Here, we report the involvement of a novel transcription factor termed 'TfoS' in this process. TfoS is a transmembrane protein that contains a large periplasmic domain and a cytoplasmic AraC-type DNA-binding domain, but lacks TCS signature domains. Inactivation of tfoS abolished natural competence as well as transcription of the tfoR gene encoding a chitin-induced small RNA essential for competence gene expression. A TfoS fragment containing the DNA-binding domain specifically bound to and activated transcription from the tfoR promoter. Intracellular TfoS levels were unaffected by disruption of chiS and coexpression of TfoS and ChiS in Escherichia coli recovered transcription of the chromosomally integrated tfoR::lacZ gene, suggesting that TfoS is post-translationally modulated by ChiS during transcriptional activation; however, this regulation persisted when the canonical phosphorelay residues of ChiS were mutated. The results presented here suggest that ChiS operates a chitin-induced non-canonical signal transduction cascade through TfoS, leading to transcriptional activation of tfoR. PMID- 24236405 TI - Total synthesis of quinaldopeptin and its analogues. AB - The first total synthesis of quinaldopeptin (1) was accomplished. Our approach to the synthesis of 1 includes the solid-phase peptide synthesis of the linear decapeptide 4 followed by macrocyclization and introduction of the quinoline chromophores 2 at a late stage of the synthesis. As for the preparation of 4, a fragment coupling approach was applied considering the C2 symmetrical structure of 1. Chromophore analogues 22 and 23 and desmethyl analogue 27 were also prepared in a manner similar to the synthesis of 1. Synthetic 1 exhibits a strong cytotoxicity with the IC50 value of 3.2 nM. On the other hand, the activity of 23 and 27 was largely reduced. PMID- 24236406 TI - Naturally split inteins assemble through a "capture and collapse" mechanism. AB - Split inteins are a class of naturally occurring proteins that carry out protein splicing in trans. The chemical mechanism of protein trans-splicing is well understood and has been exploited to develop several powerful protein engineering technologies. Split intein chemistry is preceded by efficient molecular recognition between two protomers that become intertwined in their bound state. It is currently unclear how this unique topology is achieved upon fragment association. Using biophysical techniques in conjunction with protein engineering methods, including segmental isotopic labeling, we show that one split intein fragment is partly folded, while the other is completely disordered. These polypeptides capture each other through their disordered regions and form an ordered intermediate with native-like structure at their interface. This intermediate then collapses into the canonical intein fold. This mechanism provides insight into the evolutionary constraints on split intein assembly and should enhance the development of split intein-based technologies. PMID- 24236407 TI - Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology. AB - To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs. PMID- 24236408 TI - Transition metal complexes of 3-amino-1-nitroguanidine as laser ignitible primary explosives: structures and properties. AB - 3-Amino-1-nitroguanidine (ANQ, 2) was synthesized via hydrazinolysis of nitroguanidine. By dissolving 2 in solutions containing transition metal salts, several complexes M(2+)(ANQ)2X2(H2O)y with M(2+) = Co, Ni, Cu, Zn as well as M(ANQ)2X(H2O)y with M = Ag could be isolated. In these cases, nitrate as well as perchlorate and chloride served as the respective anions X. Additionally, the ANQ complexes of Co, Ni, and Ag with dinitramide as the anion were synthesized from ANQ and silver dinitramide and by reacting the cobalt and nickel ANQ perchlorate complexes with ammonium dinitramide. The crystal structures of all described complexes were determined by low temperature single-crystal X-ray diffraction. Additionally, they were characterized using IR spectroscopy and elemental analysis. The decomposition temperatures were determined by differential scanning calorimetry and the sensitivities toward impact and friction were assessed using a BAM drophammer and a BAM friction tester (BAM = Bundesanstalt fur Materialforschung und -prufung). Additionally, the sensitivity toward electrostatic discharge was determined on a small-scale ESD device. The potential use of the nitrate, dinitramide and perchlorate containing species as primary explosives was investigated in a laser ignition test. PMID- 24236410 TI - Two cases of Marie Unna hereditary hypotrichosis: clinical features and mutation analysis of the U2HR and EPS8L3 genes. PMID- 24236411 TI - Informatics grand challenges in multi-institutional comparative effectiveness research. PMID- 24236409 TI - Cervical cancer and the global health agenda: Insights from multiple policy analysis frameworks. AB - Cervical cancer is the second leading cause of cancer deaths for women globally, with an estimated 88% of deaths occurring in the developing world. Available technologies have dramatically reduced mortality in high-income settings, yet cervical cancer receives considerably little attention on the global health policy landscape. The authors applied four policy-analysis frameworks to literature on global cervical cancer to explore the question of why cervical cancer may not be receiving the international attention it may otherwise warrant. Each framework explores the process of agenda setting and discerns factors that either facilitate or hinder policy change in cases where there is both a clear problem and a potential effective solution. In combination, these frameworks highlight a number of crucial elements that may be needed to raise the profile of cervical cancer on global health agendas, including improving local (national or sub-national) information on the condition; increasing mobilisation of affected civil society groups; framing cervical cancer debates in ways that build upon its classification as a non-communicable disease (NCD) and an issue of women's rights; linking cervical cancer screening to well-funded services such as those for HIV treatment in some countries; and identifying key global policy windows of opportunity to promote the cervical cancer agenda, including emerging NCD global health discussions and post-2015 reviews of the Millennium Development Goals. PMID- 24236412 TI - Comparative effectiveness of robotic gynecologic surgery. PMID- 24236415 TI - Improving the efficiency and outcomes of medical care. PMID- 24236414 TI - Observational studies versus randomized trials: squaring off. PMID- 24236416 TI - Improving healthcare efficiency. PMID- 24236417 TI - Stakeholder engagement in comparative effectiveness research: how will we measure success? AB - Stakeholder engagement in comparative effectiveness research continues to gain national attention. While various methods are used to gather stakeholder expertise and form recommendations, evaluation of the stakeholder experience is often missing. The lack of evaluation prohibits assessing how effective and meaningful engagement practices are for enhancing research efforts and limits the ability to identify areas for future improvement. We propose that an evaluation plan of engagement processes be developed before stakeholder involvement begins and be required as part of a request for proposal or research grant where stakeholder input is being sought. Furthermore, we recommend the inclusion of six meta-criteria that represent normative goals of multiple studies: respect, trust, legitimacy, fairness, competence and accountability. To aid in the development of future evaluations, we have developed definitions for and matched specific examples of measuring each meta-criterion to serve a guide for others in the field. PMID- 24236418 TI - Involving the public in systematic reviews: a narrative review of organizational approaches and eight case examples. AB - This paper reviews the recent literature on public involvement in the systematic review process. We examine how relevant organizations involve the public in their review processes and how the public are involved in individual reviews. We identified nine surveys or reports of public involvement in systematic reviews at an organizational level and eight examples of public involvement in individual reviews. The public was found to be involved in the following stages of the review process: topic prioritization; refining the scope of the review; suggesting, locating and appraising the literature; interpreting findings; and writing up the review. Numerous tensions, facilitating strategies and recommendations for good practice were identified. Future research directions are delineated. PMID- 24236419 TI - Struggling to bring clinical prediction rules to the point of care: missed opportunities to impact patient care. AB - Clinical prediction rules can help clinicians make personalized and complex decisions at the point of care. They have the potential to improve patient care outcomes and reduce healthcare costs, but remain underutilized. There are a number of well-derived and validated clinical prediction rules. Few, however, have been studied by means of an impact analysis or successfully integrated into provider workflow. A heavily identified area of opportunity for integration is the electronic health record. There are, however, a number of barriers to adoption at both the infrastructure and organizational levels. Research efforts should focus on impact analysis and how to successfully implement existing, well validated clinical prediction rules into daily practice. Recommendations include emphasis on a collaborative framework, using existing technologies, and utilization of usability and workflow integration methodology. PMID- 24236420 TI - Principles for planning and conducting comparative effectiveness research. AB - AIMS: To develop principles for planning and conducting comparative effectiveness research (CER). METHODS: Beginning with a modified existing list of health technology assessment principles, we developed a set of CER principles using literature review, engagement of multiple experts and broad stakeholder feedback. RESULTS & CONCLUSION: Thirteen principles and actions to fulfill their intent are proposed. Principles include clarity of objectives, transparency, engagement of stakeholders, consideration of relevant perspectives, use of relevant comparators, and evaluation of relevant outcomes and treatment heterogeneity. Should these principles be found appropriate and useful, CER studies should be audited for adherence to them and monitored for their impact on care management, patient relevant outcomes and clinical guidelines. PMID- 24236421 TI - A tall order on a tight timeframe: stakeholder perspectives on comparative effectiveness research using electronic clinical data. AB - BACKGROUND & SIGNIFICANCE: The AcademyHealth Electronic Data Methods Forum aims to advance the national dialogue on the use of electronic clinical data (ECD) for comparative effectiveness research (CER), patient-centered outcomes research, and quality improvement by facilitating exchange and collaboration among eleven research projects and external stakeholders. AcademyHealth conducted a mixed method needs assessment with the Electronic Data Methods Forum's key stakeholders to assess: stakeholder views on developing new infrastructure for CER using ECD; current gaps in knowledge with respect to CER; and expectations for a learning health system. METHODS: AcademyHealth conducted 50 stakeholder interviews between August 2011 and November 2011 with participants from the following seven stakeholder groups: government, business/payer, industry, healthcare delivery, patient/consumer, nonprofit/policy and research. With input from key collaborators, AcademyHealth designed a semi-structured interview guide and a short survey. Reviewers used the qualitative data analysis software NVivo to code the transcripts and to identify and manage complex concepts. Quantitative data from the questionnaire has been integrated with the final analysis as relevant. RESULTS: The analysis of recurring concepts in the interviews focus on five central themes: stakeholders have substantial expectations for CER using ECD, both with respect to addressing the limitations of traditional research studies, and generating meaningful evidence for decision-making and improving patient outcomes; stakeholders are aware of many challenges related to implementing CER with ECD, including the need to develop appropriate governance, assess and manage data quality, and develop methods to address confounding in observational data; stakeholders continue to struggle to define 'patient-centeredness' in CER using ECD, adding complexity to attaining this goal; stakeholders express that improving translation and dissemination of CER, and how research can be 'useful' at the point of care, can help mitigate negative perceptions of the CER 'brand'; and stakeholders perceive a need for a substantial 'culture shift' to facilitate collaborative science and new ways of conducting biomedical and outcomes research. Many stakeholders proposed approaches or solutions they felt might address the challenges identified. PMID- 24236422 TI - Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the UK, Germany, France, Spain and Italy (EU-5): results from a physician survey. AB - BACKGROUND: The differences in country-specific treatment patterns across Europe for metastatic breast cancer (mBC) patients have not been extensively studied. This study compared the treatment choices in aggregate, as well as by biomarker status, between various lines of therapy in clinical practice in the EU-5 countries among newly diagnosed mBC patients. MATERIALS & METHODS: The IMS LifeLinkTM Oncology Analyzer database, based on surveys of practicing oncologists, was used to identify mBC patients aged >=21 years. In this database, sample-level data are projected to national-level estimates for each country using a sample projection technique. RESULTS: The prevalence of hormone receptors (71-74%) is quite similar across different countries, while HER2 overexpression varies from 22 (France) to 34% (Italy); chemotherapy combined with HER2-targeted medicine was the mainstay of treatment for HER2(+) patients. The use of HER2 targeted medicine and bevacizumab greatly varied: while they were most frequently used in France, they were least frequently used in the UK. Fewer treatment options existed for triple-negative patients and patients with HER2(+) disease following trastuzumab treatment. Chemotherapy was the treatment choice for triple negative patients, as these patients do not respond to hormonal therapy and HER2 targeted medicine. CONCLUSION: This study found that, while a trastuzumab-based regimen is the preferred option for treating HER2(+) mBC patients in the EU-5, variations in this personalized medicine approach exist between different EU-5 countries. However, fewer treatment options exist for triple-negative and HER2(+) patients after trastuzumab treatment, highlighting the unmet need for these patient subgroups. PMID- 24236423 TI - The association between psychiatric diseases, psychotropic drugs and the risk of incident rosacea. AB - BACKGROUND: Psychological conditions, such as traumatic events or stress, have been discussed controversially as aetiological factors for rosacea. OBJECTIVES: To assess the association between diagnosed depression, other affective disorders or schizophrenia and subsequent incident rosacea. We further aimed at evaluating the possible role of various psychotropic drugs within this association. METHODS: We conducted a matched case-control study of psychiatric diseases and incident rosacea, stratified by exposure to various psychotropic drugs, using the UK-based General Practice Research Database. Cases had a first diagnosis of rosacea recorded between 1995 and 2009. Each case was matched to one control on age, sex, general practice and years of history on the database. RESULTS: A history of depression or other affective disorders was not associated with an increased risk of developing rosacea; lithium was the only antidepressant drug that significantly altered this association. Current long-term use of lithium was associated with a decreased odds ratio (OR) of 0.58 [95% confidence interval (CI) 0.38-0.88] among people without a schizophrenia diagnosis (with or without affective disorders), compared with people not exposed to lithium. Patients with diagnosed schizophrenia revealed a decreased rosacea risk (OR 0.71, 95% CI 0.60 0.91), independent of antipsychotic drug use. CONCLUSIONS: Depression or other affective disorders were not associated with incident rosacea, whereas patients with schizophrenia were at a decreased risk of this skin disease in our study population. The materially decreased risk of rosacea among people with chronic lithium exposure may lead to new insights into the pathomechanism of rosacea. PMID- 24236424 TI - Isolation of a new butenolide from the South China Sea gorgonian coral Subergorgia suberosa. AB - Chemical investigation on the South China Sea gorgonian coral Subergorgia suberosa has led to the isolation of one new butenolide (5R)-5-(1-ethoxypropyl)-5 hydroxy-3,4-dimethylfuran-2(5H)-one (1) as a pair of inseparable epimers, along with two known butenolides (S)-5-hydroxy-3,4-dimethyl-5-propylfuran-2(5H)-one (2) and (S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one (3). Their structures including absolute configurations were determined unambiguously by detailed analyses of spectroscopic data and by comparison with the available literature. Compounds 1-3 exhibited moderate antifouling activities against the settlement of Balanus amphitrite larvae, whereas compound 4, the acetyl derivative of 3, showed no antifouling activity at the concentrations up to 25 MUg/mL. PMID- 24236425 TI - Neutrophils: neglected players in viral diseases. AB - Increasing evidence has shown that neutrophils are able to crosstalk with various immune cells and have paradoxical roles in pathogen infections. However, the role of neutrophils in viral infections remains poorly defined. Here, the various roles that neutrophils play in viral infections and in host immunity are discussed. Various activation mechanisms of neutrophils following virus interactions and the consequences that affect disease pathogenesis are also addressed. Such knowledge not only could be used in the development of tools for clinical management but would also value-add to the current understanding of innate immunity in viral infections and disease pathogenesis. PMID- 24236426 TI - Importance of the assessment of coenzyme Q10, alpha-tocopherol and oxidative stress for the diagnosis and therapy of infertility in men. AB - Male infertility is one of the most stressful factors of couples, being present in about 40% cases. It is usually caused by a low number of sperm (oligozoospermia) or poor sperm motility (asthenozoospermia). The sperm motility is used as an indicator of semen quality and male infertility. To the impairment of male reproduction health can contribute genetic, nutritional and environmental factors, smoking and drugs. It is well documented that excessive reactive oxygen species (ROS) production decreases sperm motility, impairs sperm function, damages the morphology of spermatozoa (1, 2). To the decreased sperm motility contribute also disturbances of sperm mitochondrial function and energy production, low levels of coenzyme Q10 and carnitine, as well as sperm mitochondrial deoxyribonucleic acid (DNA) defects. The origin of sperm dysfunction, however, is not well understood. BACKGROUND: Oxidative stress has been established as a major factor in the pathogenesis of male infertility. Low level of coenzyme Q10 contributes to the decreased sperm motility, which plays a vital role in sperm mitochondrial energy production and neutralization of reactive oxygen species (ROS).The aim of the present study was to find out, if an assessment of coenzyme Q10-TOTAL (CoQ10-TOTAL), alpha-tocopherol, gamma tocopherol and oxidative stress could contribute to the diagnosis of infertility in men. SUBJECTS AND METHODS: Two groups of infertile men, according to sperm motility (a+b and b+c) were included in the study. CoQ10-TOTAL, alpha-tocopherol, gamma-tocopherol in plasma and seminal fluid, and parameter of oxidative stress (thiobarbituric acid reactive substances - TBARS) in plasma were determined. RESULTS: Higher sperm density and decreased sperm pathology were found in group a+b vs b+c (class a and b - fast and weak forward motility, class c - nonprogressive motility). Concentrations of CoQ10-TOTAL and alpha-tocopherol were significantly increased in seminal fluid of groups a+b vs b+c, opposite results were estimated in plasma. Concentrations of gamma-tocopherol in plasma and seminal fluid of both groups were similar. Plasmatic TBARS concentrations were increased in both groups of infertile men. CONCLUSION: We suppose that incorporation of oxidative stress assessment, CoQ10-TOTAL and alpha-tocopherol concentrations in seminal fluid and plasma into routine andrology can play an important role for the diagnosis and targeted therapy of male infertility (Tab. 1, Ref. 16). PMID- 24236427 TI - Evaluating the effectiveness of spleen autotransplantation into the liver and the omentum. AB - BACKGROUND: Experimental research into the viability and functionality of splenic tissue placed in the liver and the omentum. METHODS: There were 4 groups in this study. First group: sham laparotomy, 2nd group: splenectomy, 3rd group: splenectomy and splenic autotransplantation into the greater omentum and 4th group: splenectomy and splenic autotransplantation into the liver. Blood levels of haemoglobin, leukocytes, thrombocytes, immunoglobulin G (IgG), immunoglobulin M (IgM) and complement protein 3 (C3) were studied 1 day before and 6 weeks after the procedure. At the end of 6 weeks, scintigraphy was performed. Splenic tissue in the liver and the omentum were subjected to macroscopic and histopathologically. RESULTS: Pre- and postoperatively, no significant differences were found in terms of haematological and immunological measurements of groups I, III and IV. An increase in the numbers of thrombocytes and leukocytes and a decrease in the levels of IgG, IgM and C3 were observed in the postoperatively in group II.When the postoperative hematological and immunological values of the second group are compared to those of groups III and IV, the difference was significant in terms of levels of thrombocyte, leukocyte and IgM; insignificant in terms of levels of IgG and C3. In the microscopic and scintigraphic analyses the spleen tissue was found to be viable in all of the six rabbits in groups III and IV. CONCLUSIONS: The liver is a suitable organ for splenic autotransplantation (Tab. 6, Fig. 2, Ref. 17). PMID- 24236428 TI - Reduction of shock wave lithotripsy-induced renal tubular injury by tadalafil. AB - OBJECTIVES: The aim of the study was to examine whether administration of tadalafil, a phosphodiesterase type 5 inhibitor, has a protective effect in the prevention of renal injury in a rat model after Shock Wave Lithotripsy (SWL), with the assessment based on histopathologic examination and measurement of Heat Shock Protein 70 expression. METHODS: A total of 40 adult, male Sprague-Dawley rats were divided into five groups as follows; control group, group SN3, group SN7, group TSN3, TSN7. Both kidneys were evaluated regarding tubular damage, peritubular fibrosis and glomerular damage using light microscopy. We examined HSP-70 expression, which occurred in response to renal ischemic injury observed after SWL. The groups were compared between each other and with the control group. RESULTS: No statistically significant difference was found when the groups were compared using light microscopy for the changes in glomeruli. Tubular necrosis, loss of microvilli and peritubular fibrosis were less in Group TSN3 and Group TSN7 compared to Group SN3. Similarly, tubular necrosis, loss of microvilli and peritubular fibrosis were less in Group TSN3 and Group TSN7 compared to Group SN7. HSP-70 staining was less in Group TSN3 and Group TSN7 compared to Group SN3 and Group SN7. CONCLUSION: Based on the results of light microscopy and HSP-70 staining, we demonstrated that SWL could cause renal ischemia- reperfusion injury. Our results suggested that Tadalafil administration could prevent this SWL-related renal cell injury (Tab. 2, Fig. 5, Ref. 28). PMID- 24236429 TI - TNF-alpha, IL-1beta, and oxidative stress during fracture healing with or without ankaferd. AB - AIMS: Whether ankaferd blood stopper (ABS) has a negative or positive effect on bone union during fracture healing is unknown. The purpose of this study was to evaluate the serum changes of oxidative stress markers, Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-1beta (IL-1beta), and Interleukin-10 (IL-10) during fracture healing process with or without ABS application to bone fracture. MATERIAL AND METHODS: Eight rats were used as a control group (1) that was not subject to fracture. The remaining 48 rats were divided into six groups, 8 rats in each. The femoral shaft fracture was produced by cutting with bone-scissors. One ml of ABS was applied on the fracture region in groups 3 (7th day), 5 (21st day), and 7 (45th day) or saline instead of ABS on the fracture regions in groups 2 (7th day), 4 (21st day), and 6 (45th day). Radiographs and above parameters were examined on post-fracture days 7, 21, and 45. RESULTS: Malondialdehyde and protein carbonyls were measured in high levels in the groups 2 and 4 with respect to control. Their levels did not change statistically in the experimental groups after ABS application. The values of TNF-alpha and IL-1beta were elevated on 7th post-fracture day according to control, but were lower (by 11.86 % and 44.48 %) in the group 3 treated with ABS comparing to group 2. Radiographic examination indicated a low callus formation on fracture union in the femoral fractures of groups 3 and 5 treated with ABS. CONCLUSION: The present findings may suggest that ABS application seems to be ineffective on fracture union in early fracture healing period, except for bleeding control (Tab. 2, Fig. 3, Ref. 26). PMID- 24236430 TI - Antioxidative effects of adrenomedullin and vascular endothelial growth factor on lung injury induced by skeletal muscle ischemia-reperfusion. AB - PURPOSE: The aim of this study was to investigate the effects of adrenomedullin (AM) and vascular endothelial growth factor (VEGF) on lung injury as a remote organ following skeletal muscle ischemia-reperfusion injury in a rat model. MATERIALS AND METHODS: Thirty-six Wistar rats were randomized into six groups (n=6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). Ischemia reperfusion group (Group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 minutes, respectively. Group VEGF and Group AM received intravenous infusion of VEGF (0.8 MUg/kg) or AM (12 MUg /kg) respectively, without ischemia and reperfusion. Group IR+VEGF and Group IR+AM received intravenous infusion of VEGF (0.8 MUg/kg) or AM (12 MUg /kg) respectively immediately after 2 hours period of ischemia. At the end of reperfusion period. Lung tissue samples were taken for biochemical examination. Total oxidant status (TOS) and total antioxidant status (TAS) levels in lung tissue were determined by using a novel automated method. p<0.05 was considered as statistically significant. RESULTS: TOS levels were significantly higher in Group I/R, when compared with groups S, AM and VEGF (p=0.004, p=0.011, p=0.017, respectively) and significantly lower in groups I/R+AM and I/R+VEGF, when compared with Group I/R (p=0.018, p=0.006, respectively). TAS levels were significantly higher in Group I/R, when compared with groups S, AM and VEGF (p=0.006 p=0.016, p=0.016, respectively) and significantly lower in Group I/R+AM, when compared with Group I/R (p=0.016). CONCLUSION: These findings indicate that AM and VEGF acted effectively on the prevention of lung injury induced by skeletal muscle ischemia reperfusion injury in a rat model (Fig. 2, Ref. 30). PMID- 24236431 TI - Blood pressure impact on left ventricular geometry in chronic haemodialysis patients. AB - AIM: Left ventricular hypertrophy in chronic haemodialysis patients is multifactorial. Our aim was to evaluate retrospectively the relationship between 24-h blood pressure monitoring and geometry and function of left ventricle (LV). Patients a methods: We examined 50 patients (men/women 33/17) treated by chronic haemodialysis (>3 months) aged 57.5 years (53-63; median, interquartile range). We measured blood pressure during 24 hours in short interdialytic period using Spacelab monitor 90217. Echocardiography was provided in short interdialytic period. RESULTS: Left ventricular mass index significantly correlated with SBP (tau-b=0.21; p=0.030; 95%CI 0.01-0.42), DBP (tau-b=0.23; p=0.018; 95%CI 0.04 0.42) and MAP (tau-b =0.26; p=0.009; 95%CI 0.06-0.45). SBP, DBP, MAP and PP did add a significant information to the prediction of relative wall thickness. We did not find any relationship between BP and left ventricular ejection fraction, left ventricular enddiastolic diameter and left atrial size. CONCLUSION: We found out an important 24-hour blood pressure impact on left ventricular relative wall thickness and left ventricular mass index. Left ventricular ejection fraction, left ventricular enddiastolic diameter and left atrial size were not related to 24-hour blood pressure. We did not find a relationship between blood pressure and left ventricular enddiastolic diameter. From all diastolic parameters the strongest association was found between systolic blood pressure in all three phases and ratio of peak early to late diastolic filling velocity (Tab. 5, Ref. 19). PMID- 24236432 TI - Flow-mediated vasodilatation in the patients with anorexia nervosa. AB - OBJECTIVE: To compare flow-mediated vasodilatation in patients with anorexia nervosa and healthy subjects. BACKGROUND: Endothelial dysfunction is present in the patients with anorexia nervosa. However, flow-mediated vasodilatation in the patients with anorexia nervosa in comparison with control subjects has not been yet evaluated. METHODS: Flow-mediated vasodilatation in the brachial artery was examined in 30 patients with anorexia nervosa admitted to metabolic care unit for realimentation and compared to 30 control subjects. RESULTS: The average age of the patients with mental anorexia was 25.0+/-5.2 compared to 25.5+/-4.5 years of the healthy control subjects (NS). BMI was in 14.0+/-1.7 kg/m2 in patients with anorexia nervosa comparing to 20.4+/-1.0 kg/m2 in the healthy control subjects (p<0.001). The baseline mean diameter of the right brachial artery was 0.33+/ 0.06 cm in the anorexia nervosa patients and 0.35+/-0.05 cm in the control subjects (NS). The absolute increase of brachial artery size after reactive hyperemia was 0.029+/-0.006 cm (9%) in the anorexia nervosa patients and 0.039+/ 0.006 cm (11 %) in the control subjects (p=0.002). After realimentation, the baseline mean diameter of the right brachial artery was comparable to the result before nutrition intervention - 0.34+/-0.05 cm but brachial artery increase due to reactive hyperemia was 0.036+/-0.05 cm (10.5 %). It was for 19 % higher compared to the first examination (p<0.001). CONCLUSION: Flow-mediated vasodilatation is decreased in the patients with anorexia nervosa in comparison with the healthy control subjects and improves after realimentation (Tab. 1, Ref. 20). PMID- 24236433 TI - Normalization of blood lactate as early end-point of polytrauma treatment. AB - BACKGROUND: The main aim of the early treatment of polytrauma is recovery of patient's physiological functions. The early achievement of therapeutic goals, mainly adequate tissue perfusion and repayment of oxygen debt, are postulated. The aim of the study was to confirm whether blood lactate level as a quantifier of oxygen deficit, as well as normalization of blood lactate level within the first 24 hours, have an impact on the mortality and morbidity of seriously injured patients. METHODS: Sixty-nine mechanically ventilated patients with a severe trauma and organ dysfunction defined according to SOFA score and ISS >17, age >15 years, were enrolled into this retrospective study. 8 patients died within first 24 hours, 8 patients did not reach serum lactate level above 2 mmol/l on admission to hospital. The hypothesis that normalization of serum lactate level within 24 hours is related to lower mortality and morbidity, was assessed. Reduced mortality and morbidity were represented by lower severity of multi-organ dysfunction, the highest SOFA score during hospitalization, lower incidence of sepsis, number of days in ICU and artificial ventilation. RESULTS: The association between severity of multi-organ failure (p=0.0006), mortality (p=0.0022) and repayment of oxygen debt was confirmed. Hypothesis of sepsis incidence was not confirmed (p=0.34). The association between number of days on artificial ventilation and number of days in ICU to repayment of oxygen debt was not confirmed either. Multivariate significant factors were age, GCS, ISS and SOFA score on patient's admission. CONCLUSION: The patients, who repaid oxygen debt within first 24 hours, have lower morbidity and mortality (Tab. 6, Ref. 19). PMID- 24236434 TI - Complete scrotal urinary bladder hernia with both ureters and small intestine presenting as dysuria, bilateral ureterohydronephrosis, and acute renal insufficiency. AB - We report a case of a complete scrotal bladder hernia with both ureters presenting as dysuria, bilateral ureterohydronephrosis, and acute renal insufficiency. A 37-year-old man with a recurrent large scrotal mass after two surgeries, suffering with small urinary symptoms as a dysuria and nocturia, was examined before the third surgery on an outpatient basis. Urological examination revealed a negative urine, bilateral large ureterohydronephrosis on USG, and serum creatinine 231-250 umol/l. CT displayed the urinary bladder completely herniated into the scrotum with distal parts of both ureters and small intestine, and bilateral large ureterohydronephrosis. After admission to urological department on retrograde cystography a completely herniation of the urinary bladder with residual urine more than 250 ml was confirmed. A permanent catheter was indwelled. The hernia was explored with urinary bladder repositioning. Because bilateral ureteral obstruction on USG did not retreat, a bilateral percutaneous nephrostomy was done. The patient's serum creatinine markedly improved, also hernia and ureterohydronephrosis was repaired with normally moisten without residual urine (Fig. 2, Ref. 26). PMID- 24236435 TI - A comparison of Ki 67 proliferative index in primary tumor and axillary metastatic lymph nodes with length of survival in patients with breast cancer. AB - OBJECTIVE: The aim of the present study was to investigate the possibility to predict the histopathological features of breast and metastatic lymph nodes and survey and prognosis of patients and likelihood of being a predictive factor for treatment by using Ki67 immunohistochemical stain. MATERIALS AND METHODS: 95 patients who were admitted to Uludag University Medical Faculty, Department of General Surgery with a diagnosis of stage II-III breast cancer between dates May 1997 and December 2002 were retrospectively evaluated with respect to breast cancer related prognostic factors treatments and last-control related data. Ki67 immunohistochemical staining was performed to appropriate specimens using Streptavidin-biotin technique. Ki67 was reported as the proliferation index, and the number of stained nuclei were stated to be / 1000. RESULTS: In the evaluation of the lymph node by univariate analysis, we ascertained that duration of survival is shorter above the 227 cut-off value for Ki67 proliferative index. Length of survival of patients with tumor Ki67 proliferative index below 141 and with no distant metastasis was established to be better. Ki67 proliferative index in the lymph node was detected to increase more with increasing histological and nuclear grade, estrogen and progesterone receptor negativity and at stage III. CONCLUSION: Since numerous factors are effective on breast cancer, each patient and tumor behaves differently. A lot of prognostic factors are taken into account while treatment choice is determined. We may have information on the biological behavior of the tumor in patients who underwent sentinel lymph node biopsy or axillary dissection in staining with Ki67 pattern (Tab. 5, Fig. 3, Ref. 13). PMID- 24236436 TI - Primary obstructed megaureter (POM) in children. AB - The aim of this study was to analyze the results of surgical and conservative treatment of non-refluxing POM. In the period 2000-2009, 45 children (52 ureters) were treated, the average age was 5.8 months (+/-10.33), 24 children (26 ureters) by surgery (I) and 21 children (26 ureters) by conservative means (II). The average follow-up period was 73.8 (+/-32.91) and 30.85 months (+/-23.1) resp. Urine examination, USG, DTPA99mTc, biochemical testing, micturating cystouretography in all patients were performed. Significant difference was present in the occurrence of hydronephrosis of 0th, 3rd and 4th grade, p10 mm, p<0.01; and in the occurrence of normal and prolonged time T 1/2, p<0.01. The health condition was adjusted in 13 (54.20 %), improved on DTPA99mTc in 5 (20.85 %), non-improved in 3 (12.50 %), deteriorated in 1 (4.15 %) and unknown in 2 (8.3 %) patients. In the IInd group a significant difference was in case of occurrence of hydronephrosis of 0th, 2nd and 3rd grade, (p<0.01, or p=0.037 and p=0.011) and in occurrence of normal ureter, with ureter 0-5 mm and dilated ureter 5-10 mm, p<0.01. The condition at the end of the follow-up period was assessed DTPA99mTc as adjusted in 11 (52.39 %) patients, improved in 6 (28.57 %), unimproved in 3 (14.28 %) and no patient was assessed as having deteriorated and unknown in 1 (4.76 %). CONCLUSION: In patients with an impaired separate kidney function, early surgical treatment helps to minimize damage to the kidney function and prevents future complications (Tab. 6, Fig. 3, Ref. 32). PMID- 24236437 TI - Surgical treatment of nervus pudendus. AB - An objective of our work was to clarify variations in pudendal nerve formation, as well as their possible impact on the clinical picture.Bilateral pudendal nerve course and formation was studied on 20 adult cadavers. Anterior approach was used in 15 of them, both posterior and anterior approaches were used in five of them. The prefixed type plexus formation was observed in eight cases (40 %). In these cases S1, S2 roots contributed to the formation of the pudendal nerve. In the postfixed type particularly the S3 root was dominant in two cases (66.7 %), and less the S4 root in one case (23.3 %) from three cases. Mostly the S2 root participated in its formation in 17 cases (85 %). The pudendal nerve branches run below the sacrospinous ligament on the level of the sacrospinous and sacrotuberous ligaments. The changes of the nerve and the branching therof were most evident from the anterior access below the sacrospinous ligament and in front of the sacrotuberous ligament. The inferior rectal nerve penetrating the sacrospinous ligament was seen in one case, it has risen from the pudendal nerve before entering the pudendal canal in four cases. The dorsal nerve of the penis has risen from the S1 root in two cases (10 %). We observed its branching before entering the pudendal canal in 15 cases (75 %). It has divided in the pudendal canal in other cases. This description may be useful particularly for the pudendal nerve block and the nerve saving surgeries directed on the relevant region (Fig. 8, Ref. 24). PMID- 24236438 TI - The recurrent primary retroperitoneal liposarcoma. AB - AIM: Describe a patient with multiple recurrences of the primary recurrent liposarcoma. CLINICAL CASE: A 60-years-old man complained of weight loss (BMI 18.4) with a palpable huge retroperitoneal tumour, which displaced left kidney, and was confirmed on USG and CT. Laboratory examination showed anaemia and pathological blood tests. Chest X-ray initially showed a negative finding. A complete transperitonealy surgical extirpation of the tumour with left side nephrectomy was performed on June 28, 2007. The tumour mass weight was 1900 g. It was lying on the posterior face of the kidney in diameters 170x120x120 mm, completely capsulated by thin grey-pink capsula with peripheral fat tissue on the section grey-pink, lobulary shaped, in 3/4 parts with central necrotic changes. Histopathologically was confirmed the primary dedifferentiated (non-lipogenous) liposarcoma low grade of malignancy. Nephrectomy specimen was confirmed as age related finding. There was no evidence of positives surgical margins. Despite oncological and surgical treatment, followed repeated recurrence with eight transperitoneal surgeries in the retroperitoneum and abdomen with extirpation of the metastases, left side hemicolectomy, splenectomy and repeated extirpation tumour metastases from abdomen and radix mesenterii. Last tumour weighed 2900 grams. Patient died on January 9, 2011, after the eight surgeries on multiorgans failure due to hemorrhagic shock and persistent atrial fibrilaton by cardiopulmonary insufficiency. As a speciality, he was treated without transfusion because as Jehovah's witness he refused blood derivates. CONCLUSION: Despite complex surgical and oncological treatment, the prognosis in patient with recurrent liposarcoma was fatal (Tab. 1, Fig. 5, Ref. 50). PMID- 24236439 TI - Alterations in paraoxonase-1 activity. PMID- 24236440 TI - The proteome differences - new trend of placenta examination. PMID- 24236441 TI - Comparison of thoracic auscultation, clinical score, and ultrasonography as indicators of bovine respiratory disease in preweaned dairy calves. AB - BACKGROUND: The diagnostic tools for bovine respiratory disease diagnosis include clinical inspection, thoracic auscultation, and ultrasonography. HYPOTHESIS: Thoracic auscultation and clinical examination have limitations in the detection of lung consolidation in dairy calves. ANIMALS: Prospective cohort of 106 preweaned calves from 13 different dairy herds (10 with a history of active bovine respiratory disease (BRD) in calves and 3 without suspected BRD problems). METHODS: Each preweaned calf was clinically inspected using the Wisconsin calf respiratory scoring chart (CRSC) and treatment history was noted. Systematic thoracic auscultation and ultrasonography then were performed, the latter focusing on lung consolidation. Mortality was recorded over a 30-day period. RESULTS: A total of 56 of 106 calves had ultrasonographic evidence of lung consolidation. The sensitivity of thoracic auscultation to detect consolidation was 5.9% (range, 0-16.7%). Only 41.1% (23/33) of calves with consolidated lungs had been treated previously by the producers. When adding CRSC and previous BRD treatment by the producer, sensitivity of detection increased to 71.4% (40/56). The area under the receiver operating characteristics curve was 0.809 (95% CI, 0.721-0.879) for the number of areas within the lungs with consolidation and 0.743 (95% CI, 0.648-0.823) for the maximal depth of consolidation as predictors of death within 1 month after examination. These were not significantly different (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows that thoracic auscultation is of limited value in diagnosing lung consolidation in calves. Ultrasonographic assessment of the thorax could be a useful tool to assess BRD detection efficiency on dairy farms. PMID- 24236442 TI - Development of dual-setting calcium phosphate cement using absorbable polymer. AB - Calcium phosphate cements used as bone substitutes generally have low mechanical strength compared with the bones of the human body. To solve these needs, we have incorporated hydrogels in the manufacture of samples made of alpha-tricalcium phosphate (alpha-TCP) cement, developing a system of dual-setting cement. This study aimed to produce composite materials by combining alpha-TCP powder and hydrogels. The composites were prepared using the synthesized powder and four different formulations of hydrogels, using either poly(N-vinyl-2-pyrrolidone) or poly(N-vinyl-2-pyrrolidone-co-acrylic acid), with either azobisisobutyronitrile or ammonium persulfate as initiator. The properties of all composites were evaluated through measuring compressive strength and apparent density and through X-ray diffraction and scanning electron microscopy. The composites showed compressive strengths of around 24 MPa. Soaking the samples in simulated body fluid formed a layer of hydroxyapatite-like crystals on the surface of some samples, showing the bioactivity of the newly developed cements and their potential use as biomaterial. PMID- 24236443 TI - Pathways to adulthood and their precursors and outcomes. AB - Norway has an extensive welfare system which may provide adolescents with many options and high levels of flexibility in terms of pathways to adulthood. This study aimed to describe Norwegian developmental pathways to adulthood, including changes in role statuses (such as living situations, education, work, marriage/cohabitation and parenthood) from 16 to 30 years of age, and their precursors and outcomes. Repeated measures latent class analysis of longitudinal data from 998 Norwegian individuals indicated three main pathways to adulthood among women and men. In both sexes, most individuals undertook a long period of education and postponed family formation. However, some individuals started working early, a group of women established families with partners and children early, and a group of men remained primarily single between 16 and 30 years of age. Furthermore, the results show that pathways to adulthood in Norway are surprisingly similar to pathways in other countries such as the US, UK and Finland. The results indicate that pathways to adulthood are influenced by social reproduction factors in a country with high levels of welfare benefits as well. In addition, the results suggest that pathways involving living with a partner and either higher education or work are associated with high life satisfaction at age 30. PMID- 24236445 TI - Multiphoton microscopic imaging of human normal and cancerous oesophagus tissue. AB - In this paper, microstructures of human oesophageal submucosa are evaluated using multiphoton microscopy, based on two-photon excited fluorescence and second harmonic generation. The content and distribution of collagen, elastic fibers and cancer cells in normal and cancerous submucosa layer have been distinctly obtained and briefly discussed. The variation of these components is very relevant to the pathology in oesophagus, especially in early oesophageal cancer. Our results further indicate that the multiphoton microscopy technique has the potential application in vivo in clinical diagnosis and monitoring of early oesophageal cancer. PMID- 24236444 TI - PSK1 regulates expression of SOD1 involved in oxidative stress tolerance in yeast. AB - The Per-ARNT-Sim (PAS) domain serine/threonine kinase PAS kinase is involved in energy flux and protein synthesis. In yeast, PSK1 and PSK2 are two partially redundant PASK homologs. We recently generated PSK2 deletion mutant and showed that Psk2 acts as a nutrient-sensing protein kinase to modulate Ultradian clock coupled respiratory oscillation in yeast. Here, we show that deletion of PSK1 increased the sensitivity of yeast cells to oxidative stress (H2 O2 treatment) and partially inhibited cell growth; however, the growth of the PSK2-deleted mutant was similar to that of the wild type. Superoxide dismutase-1 (SOD1) mRNA and protein levels were lower in PSK1-deletion mutant than the wild type. The mRNA levels of stress response genes CTT1, HSP104, ATH1, NTH1 and SOD2 were similar in both the PSK1-deleted mutant and wild-type yeast. Furthermore, intracellular accumulation of reactive oxygen species (ROS) was noted in PSK1 deleted mutant. These results suggest that PSK1 induces SOD1 expression to protect against oxidative stress in yeast. PMID- 24236446 TI - Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study. AB - BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients. PMID- 24236448 TI - Prospective review of a single center's general pediatric neurosurgical intraoperative and postoperative complication rates. AB - OBJECT: The authors conducted a study to compare the complication rate (CR) of pediatric neurosurgical procedures in a general neurosurgery department to the CRs that are reported in the literature and to establish a baseline of CR for further targeted improvement of quality neurosurgical care. METHODS: The authors analyzed the prospectively collected data from a complication registration of 1000 consecutive pediatric neurosurgical procedures in 581 patients from the beginning of the registration in January 2004 through August 2008. A pediatric neurosurgeon was involved in 50.5% of the procedures. All adverse events (AEs) from induction of anesthesia until 30 days postoperatively were recorded. RESULTS: Overall, 229 complications were counted in 202 procedures. The overall CR was 20.2%, with a 2.7% intraoperative CR and a 17.5% postoperative CR. Tumor surgery was associated with the highest CR (32.7%), followed by CSF disorders (21.8%). The mortality rate was 0.3%. An unplanned return to the operating room in relation to an AE happened in 10.5% of all procedures and in 52% of procedures associated with AEs, the majority of which were related to CSF disorders. CONCLUSIONS: The CR in pediatric neurosurgical procedures was significant, and more than half of the patients with an AE required a repeat surgical procedure. Analysis of CRs should be a prerequisite for the prevention of complications and for the development of targeted interventions to reduce the CR (for example, infection rates). PMID- 24236447 TI - Establishment of a multidisciplinary concussion program: impact of standardization on patient care and resource utilization. AB - OBJECT: Recent legislation and media coverage have heightened awareness of concussion in youth sports. Previous work by the authors' group defined significant variation of care in management of children with concussion. To address this variation, a multidisciplinary concussion program was established based on a uniform management protocol, with emphasis on community outreach via traditional media sources and the Internet. This retrospective study evaluates the impact of standardization of concussion care and resource utilization before and after standardization in a large regional pediatric hospital center. METHODS: This retrospective study included all patients younger than 18 years of age evaluated for sports-related concussion between January 1, 2007, and December 31, 2011. Emergency department, sports medicine, and neurosurgery records were reviewed. Data collected included demographics, injury details, clinical course, Sports Concussion Assessment Tool-2 (SCAT2) scores, imaging, discharge instructions, and referral for specialty care. The cohort was analyzed comparing patients evaluated before and after standardization of care. RESULTS: Five hundred eighty-nine patients were identified, including 270 before standardization (2007-2011) and 319 after standardization (2011-2012). Statistically significant differences (p < 0.0001) were observed between the 2 groups for multiple variables: there were more girls, more first-time concussions, fewer initial presentations to the emergency department, more consistent administration of the SCAT2, and more consistent supervision of return to play and return to think after adoption of the protocol. CONCLUSIONS: A combination of increased public awareness and legislation has led to a 5-fold increase in the number of youth athletes presenting for concussion evaluation at the authors' center. Establishment of a multidisciplinary clinic with a standardized protocol resulted in significantly decreased institutional resource utilization and more consistent concussion care for this growing patient population. PMID- 24236449 TI - Association of cerebellopontine angle atypical teratoid/rhabdoid tumors with acute facial nerve palsy in infants. AB - Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS tumors found almost exclusively in childhood. Although essentially universally fatal when incompletely resected, prompt diagnosis followed by early chemoradiation can improve outcomes. An AT/RT can occur extraaxially at the cerebellopontine angle (CPA) and cause acute cranial nerve deficits as the presenting sign. The authors report a series of 3 children who presented with isolated acute facial nerve palsies and in whom subsequent diagnosis of a CPA AT/RT was made. The authors propose that in young children whose presenting symptom is an acute facial nerve palsy with a CPA tumor, AT/RT should be highly suspected. PMID- 24236450 TI - Identification of a novel frame-shift mutation in PRSS1 gene in Han patients with autoimmune pancreatitis. AB - OBJECTIVE: To detect mutations of trypsinogen gene (PRSS1) in patients with autoimmune pancreatitis (AIP) and to determine the underlying pathogenesis. METHODS: DNA sequencing was used to detect full-length of PRSS1, cystic fibrosis transmembrane conductance regulator (CFTR), and pancreatic secretory trypsin inhibitor (SPINK1) genes mutations in an AIP family and a sporadic case and 520 normal controls. Furthermore, a mutant-expressing system was constructed for functional confirmation. RESULTS: For the first time, we report a deletion mutation at exon 2 of PRSS1 gene (IVS 2 +56_60 del CCCAG) which encoded a truncated PRSS1 protein without trypsinogen activation peptide (TAP). Vitro functional study suggested the identified mutation would result in loss of PRSS1 activity. Mutant trypsinogen activated at a faster rate than wild-type trypsinogen in the autoactivation experiment. Histopathologic examination revealed the ratio of IgG4/IgG-positive plasma cells exceeded 0.455 in pancreas, and the patients responded to glucocorticoids. CONCLUSION: PRSS1: IVS 2 +56_60 del CCCAG is a noval mutant which may contribute to AIP pathogenesis. PMID- 24236451 TI - Pleiotropic effects of HDL: towards new therapeutic areas for HDL-targeted interventions. AB - Plasma levels of high density lipoprotein (HDL) cholesterol levels and of apolipoprotein A-I are inversely correlated with the incidence of coronary heart disease. According to the HDL hypothesis, raising HDL cholesterol is expected to lead to a decrease of coronary heart disease risk. The stringent requirement for proving or refuting this hypothesis is that the causal pathway between the therapeutic intervention and a hard clinical end-point obligatory passes through HDL. The lack of positive clinical results in several recent HDL trials should be interpreted in light of the poor HDL specificity of the drugs that were investigated in these trials. Nevertheless, the results of Mendelian randomization studies further raise the possibility that the epidemiological relationship between HDL cholesterol and coronary artery disease might reflect residual confounding. HDL are circulating multimolecular platforms that exert divergent functions: reverse cholesterol transport, antiinflammatory effects, anti-oxidative effects, immunomodulatory effects, improved endothelial function, increased endothelial progenitor cell number and function, antithrombotic effects, and potentiation of insulin secretion and improvement of insulin sensitivity. Pleiotropic effects of HDL might be translated in clinically significant effects in strategically selected therapeutic areas that are not directly related to native coronary artery disease. In this review, four new therapeutic areas for HDL-targeted diseases are presented: critical illness, allograft vasculopathy and vein graft atherosclerosis, type 2 diabetes mellitus, and heart failure. The strategic selection of these therapeutic areas is not only based on specific functional properties of HDL but also on significant pre clinical and clinical data that support this choice. PMID- 24236452 TI - Endothelial remodelling and intracellular calcium machinery. AB - Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel. PMID- 24236453 TI - Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model. AB - Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic progenitor cell (oval cell in rodents) population might be considered as an alternative mean to enhance liver functional recovery. Vitamin K2 has been shown to promote liver functional recovery in patients with liver cirrhosis. In this study, we explored the possibility of vitamin K2 treatment in activating hepatic oval cell for liver regeneration with the classic 2-acetamido-fluorene/partial hepatectomy (2-AAF/PH) model in Sprague-Dawley rats. In 2-AAF/PH animals, vitamin K2 treatment induced a dose-dependent increase of liver regeneration as assessed by the weight ratio of remnant liver versus whole body and by measuring serum albumin level. In parallel, a drastic expansion of oval cell population as assessed by anti-OV6 and anti-CK19 immunostaining was noticed in the periportal zone of the remnant liver. Since matrilin-2 was linked to oval cell proliferation and liver regeneration after partial hepatectomy, we assessed its expression at both the mRNA and protein levels. The results revealed a significant increase after vitamin K2 treatment in parallel with the expansion of oval cell population. Consistently, knocking down matrilin-2 expression in vivo largely reduced vitamin K2-induced liver regeneration and oval cell proliferation in 2-AAF/PH animals. In conclusion, these data suggest that vitamin K2 treatment enhances liver regeneration after partial hepatectomy, which is associated with oval cell expansion and matrilin-2 up-regulation. PMID- 24236455 TI - BST-2 expression in human hepatocytes is inducible by all three types of interferons and restricts production of hepatitis C virus. AB - Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin, CD317, or HM1.24) has recently been identified as a host restriction factor against diverse families of enveloped viruses. However, the effects of BST-2 on the life cycle of hepatitis C virus (HCV), an enveloped RNA virus, remain unclear and controversial. Here we demonstrated that human hepatocytes including Huh7.5.1 cells, primary human hepatocytes (PHHs), and HepG2 cells constitutively expressed low to moderate levels of endogenous BST-2 on the cell surface, which could be robustly up-regulated by all three types of interferons (IFNs) such as IFN-alpha, IFN-gamma, and IFN-lambda. IFN-alpha and IFN-gamma showed a synergistic effect in induction of BST-2 expression on human hepatocytes. Over-expression of BST-2 by BST-2-expressing vector transfection or up-regulation of BST-2 by IFN stimulation markedly suppressed HCV production, whereas shRNA-mediated depletion of endogenous BST-2 significantly enhanced HCV production in infected Huh7.5.1 cells. IFN-mediated anti-HCV activity was partially but significantly diminished by shRNA-mediated knockdown of BST-2 expression, indicating that BST- 2 upregulation is directly involved in IFN-mediated inhibition of HCV production. We also found that both BST-2 and HCV core co-localized with intracellular lipid droplets (LDs), suggesting that BST-2-HCV interaction may take place around LDs as LDs constitute an important intracellular organelle for HCV assembly and replication. Taken together, our data suggest that BST-2 is a host restriction factor against HCV, and induction of BST-2 in hepatocytes could be one of the mechanisms by which current HCV standard therapy (IFN-alpha plus ribavirin) achieves a sustained virological response (SVR). PMID- 24236456 TI - Inhibition of topoisomerase I by anti-cancer drug altered the endometrial cyclicity and receptivity. AB - Topoisomerase I (topo I) is an essential nuclear enzyme involved in virtually all aspects of gene expression, and is the target of the anti-cancer drugs- camptothecin (CPT) and its derivatives. Improvement of the survival rates of young women with cancer has led to the consideration of the effects of long-term chemotherapy on their fertility. The effect of anticancer drugs on ovarian function was previously investigated; however, no reports are available concerning their effect on the endometrium, whose integrity is an important factor in embryo implantation. Here we used a rat animal model to investigate the expression and activity of topo I in the various physiologic phases of the endometrium and the influence of CPT on its integrity and receptivity. The results show, for the first time, that the endometrial topo I level and activity are influenced by the physiologic phases of the endometrium (estrous cycle) and correlate with the estrogen blood concentration. Treatment with the anti-cancer drug CPT caused histological disruption of the endometrium and deleterious effect on its cyclicity. Moreover, CPT treatment significantly reduced the implantation rate of embryos, suggesting alteration in the receptivity of the endometrium. These results suggest that topo I is important for maintaining the normal physiologic cyclicity and functionality of the endometrium in rats. Anti-cancer agents that target topo I severely impair estrous cycle progression and endometrial integrity and receptivity, emphasizing the importance of addressing the effect of chemotherapy on the endometrial functionality. PMID- 24236454 TI - Novel adjunctive therapies for the treatment of tuberculosis. AB - Despite significant efforts to control tuberculosis (TB), the disease remains a major global threat, with an estimated 8.6 million new cases and 1.3 million deaths in 2012 alone. Significant treatment challenges include HIV co-infection, the dramatic rise of multidrug-resistant TB and the vast reservoir of latently infected individuals, who will develop active disease years after the initial infection. The long duration of chemotherapy also remains a major barrier to effective large scale treatment of TB. Significant advances are being made in the development of shorter and effective TB drug regimens and there is growing evidence that host-directed and "non-antimicrobial" pathogen-directed therapies, could serve as novel approaches to enhance TB treatments. This review highlights the rationale for using these therapies and summarizes some of the progress in this field. PMID- 24236457 TI - Chemoprevention gene therapy (CGT) of pancreatic cancer using perillyl alcohol and a novel chimeric serotype cancer terminator virus. AB - Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers. To enhance the efficacy of the CTV-M7, we generated a chimeric Ad.5 and Ad.3 modified fiber bipartite CTV (Ad.5/3-CTV-M7) that can infect tumor cells in a Coxsackie Adenovirus receptor (CAR) independent manner, while retaining high infectivity in cancer cells containing high CAR. Although mda-7/IL-24 displays broad-spectrum anticancer properties, pancreatic ductal adenocarcinoma (PDAC) cells display an intrinsic resistance to mda-7/IL-24-mediated killing due to an mda-7/IL-24 mRNA translational block. However, using a chemoprevention gene therapy (CGT) approach with perillyl alcohol (POH) and a replication incompetent Ad to deliver mda-7/IL-24 (Ad.mda-7) there is enhanced conversion of mda-7/IL-24 mRNA into protein resulting in pancreatic cancer cell death in vitro and in vivo in nude mice containing human PDAC xenografts. This combination synergistically induces mda-7/IL-24-mediated cancer-specific apoptosis by inhibiting anti apoptotic Bcl-xL and Bcl-2 protein expression and inducing an endoplasmic reticulum (ER) stress response through induction of BiP/GRP-78, which is most evident in chimeric-modified non-replicating Ad.5/3- mda-7- and CTV-M7-infected PDAC cells. Moreover, Ad.5/3-CTV-M7 in combination with POH sensitizes therapy resistant MIA PaCa-2 cell lines over-expressing either Bcl-2 or Bcl-xL to mda 7/IL-24-mediated apoptosis. Ad.5/3-CTV-M7 plus POH also exerts a significant antitumor 'bystander' effect in vivo suppressing both primary and distant site tumor growth, confirming therapeutic utility of Ad.5/3-CTV-M7 plus POH in PDAC treatment, where all other current treatment strategies in clinical settings show minimal efficacy. PMID- 24236458 TI - The molecular basis of notch signaling regulation: a complex simplicity. AB - The Notch receptors have attracted considerable attention for their ability to control cellular functions that regulate embryo development and tissue homeostasis. Notch receptors act by controlling the expression of a specific set of target genes. If Notch signaling system can be so simple, and yet so complex in its pleiotropic effects, then a sophisticated network of regulatory mechanisms is required to maintain the control over the initiation, activity and termination of this signaling pathway. A multitude of regulatory mechanisms has been discovered that controls the interaction of Notch receptors with their ligands, the assembling of a Notch transcriptional activation complex and the termination of Notch signals. The intracellular and extracellular domains of the Notch receptors are synthesized as single proteins, pairing with each other during their trafficking through the exocytotic route. The mechanisms operating in the phase preceding the generation of the heterodimeric signal-competent Notch receptors can be as elaborate and physiologically important as those operating downstream of Notch receptor activation. These regulatory mechanisms, which are essential to understand the role of Notch signaling in human physiology and pathology are reviewed here. PMID- 24236459 TI - Hypothalamic mTOR: the rookie energy sensor. AB - Optimal cellular function and therefore organism's survival is determined by the sensitive and accurate convergence of energy and nutrient abundance to cell growth and division. Among other factors, this integration is coupled by the target of rapamycin (TOR) pathway, which is able to sense nutrient, energy and oxygen availability and also growth factor signaling. Indeed, TOR signaling regulates cell energy homeostasis by coordinating anabolic and catabolic processes for survival. TOR, named mTOR in mammals, is a conserved serine/threonine kinase that exists in two different complexes, mTORC1 and mTORC2. Recently, studies are suggesting that alterations of those complexes promote disease and disrupted phenotypes, such as aging, obesity and related disorders and even cancer. The evidences linking mTOR to energy and metabolic homeostasis included the following. At central level mTOR regulates food intake and body weight being involved in the mechanism by which signals such as leptin and ghrelin exert its effects. At peripheral level it influences adipogenesis and lipogenesis in different tissues including the liver. Noteworthy chronic nutritional activation of mTOR signaling has been implicated in the development of beta cell mass expansion and on insulin resistance. Understanding of mTOR and other molecular switches, such as AMP-activated protein kinase (AMPK), as well as their interrelationship is crucial to know how organisms maintain optimal homeostasis. This review summarizes the role of hypothalamic TOR complex in cellular energy sensing, evidenced in the last years, focusing on the metabolic pathways where it is involved and the importance of this metabolic sensor in cellular and whole body energy management. Understanding the exact role of hypothalamic mTOR may provide new cues for therapeutic intervention in diseases. PMID- 24236460 TI - The protein-protein interaction-mediated inactivation of PTEN. AB - PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol-3 Kinase (PI3K). PI3K functions in numerous pathways and cellular processes, including tumourigenesis. Therefore, mechanisms regulating PTEN function, either positively or negatively are of great interest not only to oncogenesis but also to other aspects of human health. Since its discovery in 1997, PTEN has been one of the most-heavily studied tumour suppressors and has been the subject of numerous reviews. Most investigations and reviews center on PTEN's function and its regulation. While the regulation of PTEN function via genetic and/or epigenetic mechanisms has been extensively studied, the impact of protein-protein interaction on PTEN function remains less clear. Recent research has revealed that PTEN can be specifically inhibited by its interaction with other proteins, which are collectively termed PTEN-negative regulators (PTENNRs). This review will summarize our current understanding on the protein network that influences PTEN function with a specific focus on PTEN-NRs. PMID- 24236461 TI - Alkaloids as aldose reductase inhibitors, with special reference to berberine. AB - Aldose reductase is the rate-limiting enzyme of the polyol pathway that leads to conversion of glucose to sorbitol. Its increased activity, which results in abnormal activation of the polyol pathway, is implicated in the development of long-term complications of diabetes mellitus. Different plant species and their active components have shown potent in vitro and in vivo aldose reductase inhibitory activity. Among different phyto-constituents, alkaloids that contain isoquinoline/bis(isoquinoline)and related ring structures (such as berberine, palmatine, coptisine, and jateorrhizine) have shown very potent aldose reductase inhibitory activity. The structural activity relationship has revealed the importance of hydrophobic and hydrophilic groups of isoquinoline/bis(isoquinoline)for binding to an enzyme. The dioxymethylene group in the D ring (hydrophobic group) of these alkaloids binds tightly to the site adjacent to the anionic binding site (active site), while the methoxyl groups (polar) bind to the site adjacent to the nicotinamide ring of the coenzyme. On the basis of these findings, it may be proposed that the presence of isoquinoline/bis(isoquinoline)ring structures is the most important requirement for alkaloids to behave as potent aldose reductase inhibitors. Thus, other plants may also be screened for the same activity. The present review discusses these isoquinoline/bis(isoquinoline)-based alkaloids as aldose reductase inhibitors that may be used to manage diabetic complications and may substitute for the chemically synthesized aldose reductase inhibitors. PMID- 24236462 TI - Gathering data from older adults via proxy respondents: research challenges. PMID- 24236464 TI - From methods to policy: past as prologue: how comparative effectiveness research became patient-centered outcomes research. PMID- 24236465 TI - Maximizing health through the rapidly developing fields of comparative and cost effectiveness. AB - Lieven Annemans is a Full Professor of Health Economics at Ghent University and Brussels University (Belgium) and cofounder of the Interuniversity Centre for Health Economics Research. He is Past-President of the International Society for PharmacoEconomics and Outcomes Research, a member of the Flemish Council for Health and Wellbeing (advising the Minister of Health), and an external expert to the Belgian Health Care Knowledge Centre, the Belgian health technology assessment body. He has 20 years experience in health-economic evaluations of pharmaceutical drugs, vaccines, medical devices, diagnostics and preventive health actions in various medical areas. He is author of the book 'Health economics for noneconomists: an introduction to the concepts, methods and pitfalls of health economic evaluations' and of the recent report 'Towards valuable innovation in the EU' (a background report to the EU council of ministers of health). His main research interests are epidemiological models, health technology assessment, retrospective/prospective health-economic evaluations and physician payment systems. He has published approximately 150 papers in peer-reviewed journals, presented approximately 300 posters/papers at scientific conferences, and has given approximately 500 lectures and trainings on health economics and health technology assessment. PMID- 24236466 TI - Comparative effectiveness of biologic antirheumatic therapies in rheumatoid arthritis after failure to respond to a first TNF inhibitor. AB - Evaluation of: Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-201324 (2012) (Epub ahead of print). Rheumatoid arthritis is a chronic immune-mediated disease affecting approximately 1% of the population. The prognosis of this chronic condition has considerably improved over the past decade with the earlier use of antirheumatic drugs and the introduction of new biologic therapies. Current treatment guidelines recommend using these agents after a failed response to conventional disease-modifying antirheumatic drugs, but the relative positioning of the various available biologic agents is not yet well established. All biologic agents have been proven to be superior to placebo in large trials, but only very few randomized controlled trials have compared directly competing therapeutic options. This article evaluates the effectiveness of rituximab compared with an alternative TNF antagonist (anti-TNF) in rheumatoid arthritis patients who experienced a previous failed response to anti-TNF. The results of this large observational cohort study suggest that rituximab offers a greater benefit on rheumatoid arthritis disease activity than alternative monoclonal anti-TNFs. PMID- 24236467 TI - Anti-VEGF therapies for the treatment of age-related macular degeneration. AB - Evaluation of: Martin DF, Maguire MG, Fine SL et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration two-year results. Ophthalmology 119(7), 1388-1398 (2012). Age-related macular degeneration is the leading cause of blindness in European-derived populations. Recently, drugs have been developed that not only reduce the risk of vision loss, but can actually improve visual acuity. This article provides a summary of a recent comparative effectiveness trial evaluating two of these drugs. The study found that visual acuity outcomes were similar for the two drugs and that monthly dosing provided a slight advantage over as-needed treatment. The role of long-term differences in retinal thickening, geographic atrophy and potential differences in serious adverse events between the two drugs need further research. PMID- 24236468 TI - Comparing methods of respiratory event detection during the treatment of obstructive sleep apnea. AB - Renewed focus on comparative effectiveness research presents a unique opportunity to develop optimal clinical management pathways for patients with obstructive sleep apnea. With this momentum comes the challenge of measuring treatment effect on sleep-disordered breathing, especially in large, multisite studies. In laboratory polysomnography, the current gold standard sleep assessment of obstructive sleep apnea severity, is costly and imposes significant participant burden. Alternatives include home unattended sleep testing and overnight pulse oximetry recording. Research studies using positive airway pressure treatment have the additional option of using the information recorded by the patient's positive airway pressure device to assess treatment effectiveness. Recent research has shown relatively good agreement between manual identification of residual respiratory events in overnight in-laboratory polysomnography and the automatic event detection utilized in positive airway pressure machines. In addition to assessing the effects of interventions on sleep disordered breathing, obstructive sleep apnea-related comparative effectiveness studies need to assess the impact of the interventions on patient burden, cost of therapy, timeliness of care, improved quality of life and other clinically relevant outcomes. PMID- 24236469 TI - Drug-eluting versus bare-metal coronary stents: where are we now? AB - Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents). PMID- 24236470 TI - The utilization of telephone follow-up in the advanced cancer population: a review of the literature. AB - BACKGROUND: Palliative cancer patients often require clinic or hospital follow-up after any treatment intervention they may have received. This is typically done in person at either a hospital or a clinic. In these advanced cancer patients, this may be burdensome and result in attrition. Telephone follow-up is becoming more frequently used as an adjunct to clinical follow-up. It can be conducted for both clinical trials, as well as interventional purposes. The purpose of this study was to review the literature and examine the utility and effectiveness of telephone follow-up in the advanced cancer population. METHODS: A literature search was conducted on Medline (1980 - April week 4 2012), Embase (1980 - week 17 2012), the Cochrane Central Register of Controlled Trials (April 2012) and CINAHL (1981-July 31 2012). RESULTS: A total of 11 studies were identified that were published between 2001 and 2011. All studies were in the clinical trial setting. Studies that utilized telephone follow-up in the advanced cancer population, as well as studies that compared the feasibility of telephone follow up with hospital follow-up, were included in this review. Follow-up at week 4 (month 1) was the most common interval for patient contact. Information collected during the contact varied with the study; however, the most commonly used tool was the Edmonton Symptom Assessment System. Other information included analgesic diary, patient feedback, satisfaction with the care and post-treatment side effects, along with a variety of quality of life questionnaires. Some studies provided information to the patient about protocols for care, advice and coping strategies. Attrition was common even with the use of telephone contact in place of clinical follow-up. CONCLUSION: Telephone follow-up is a feasible alternative to traditional hospital follow-ups for assessment of symptom palliation. There are fewer burdens on the patient, allowing for a better maintenance of quality of life and lower rates of attrition in clinical trials. Patients had an overall positive opinion of the use of this alternative approach with no common disadvantages. A combination of follow-up strategies, such as clinic follow-up and telephone contact for those not attending, may result in a more comprehensive assessment. PMID- 24236471 TI - What do researchers say about proposed Medicare claims public use files? AB - BACKGROUND: Medicare claims data sets have been used widely in outcomes research over the last decade. In 2010, the Centers for Medicare & Medicaid Services established a program to create de-identified basic standalone public use files (PUFs) from Medicare claims data, each one containing claims information from a 5% sample of beneficiaries. METHODS: We conducted a series of structured key informant interviews with research stakeholders to compile recommendations that would guide the creation of these PUFs. In this paper, we describe the interview methodology and present our findings. Fifteen researchers, representing a range of clinical health services and health policy expertise, were interviewed. RESULTS: All respondents supported the use of Medicare claims in comparative effectiveness research and responded favorably to the creation of PUFs for this purpose. The interviews resulted in administrative-, technical- and content related recommendations, some of which led to important changes in the PUFs. DISCUSSION: A primary trade-off in the development of the proposed PUFs involved assuring maximum research utility of the files while assuring security of beneficiaries' protected health information. Protection of protected health information was considered a requirement. Given this constraint, the proposed PUFs may be most useful for two primary activities in comparative effectiveness research: first, working through the beginning stages of a research project; and second, examining high-level questions. PMID- 24236472 TI - Ongoing measures to enhance the efficiency of prescribing of proton pump inhibitors and statins in The Netherlands: influence and future implications. AB - BACKGROUND: Multiple reforms have recently been introduced in The Netherlands to improve prescribing efficiency. These include preference pricing policies for multiple sourced products, guidelines, and quality and efficiency targets, as well as regular pharmacotherapy meetings. OBJECTIVES: Assess the influence of these multiple measures on prescribing efficiency. METHODS: Retrospective observational study of all reimbursed prescriptions for proton pump inhibitors and statins between 2000 and 2010 using the Genees-en hulpmiddelen Informatie Project (Health Insurance) database. Utilization measured in defined daily doses. Narrative review of reforms. RESULTS: Reimbursed expenditure for the proton pump inhibitors fell by 58% in 2010 versus 2000 despite a threefold increase in utilization, helped by increasing utilization of generic omeprazole at only 2% of the prepatent loss price in 2010. Similarly, reimbursed expenditure for the statins fell by 14% in 2010 versus 2000 despite a 3.8-fold increase in utilization. Again, this was helped by increasing utilization of generic simvastatin at only 2% of the prepatent loss originator price. CONCLUSION: Multiple supply and demand measures, including the preference pricing policy, appear to have appreciably enhanced proton pump inhibitor and statin prescribing efficiency, providing examples to other countries. PMID- 24236473 TI - Possible ways to enhance renin-angiotensin prescribing efficiency: Republic of Serbia as a case history? AB - BACKGROUND: Multiple reforms have been instigated across Europe to enhance prescribing efficiency. Supply-side reforms in the Republic of Serbia include measures to lower the price of generics and originators, with demand-side measures including patient copayments and prescribing restrictions. Specific measures for renin-angiotensin inhibitor drugs include a 50% copayment for angiotensin receptor blockers (ARBs) versus approximately 50 cents per prescription for established angiotensin-converting enzyme inhibitors (ACEIs), as there is no perceived difference in effectiveness between the two classes. OBJECTIVES: To assess the influence of these measures on ARB utilization, as well as reimbursed prices of ACEIs and ARBs over time. METHOD: Observational retrospective case study of all ambulatory care patients in the Republic of Serbia's Health Insurance Fund database who were dispensed at least one ACEI or ARB alone or in combination (fixed dose combination [FDC]) between 2005 and 2011. Utilization measured in defined daily doses (DDDs) and only reimbursed expenditure (overall and expenditure/DDD) as Health Insurance perspective. RESULTS: There was a 1.8-fold increase in renin-angiotensin inhibitor drug utilization, rising to 207.4 DDDs/1000 inhabitants per day in 2011. This is driven principally by a 19.6-fold increase in ACEI FDCs. There was only limited utilization of ARBs at just 2% of total renin-angiotensin inhibitor drugs in 2011. Reimbursed expenditure increased 2.54-fold due to an appreciable increase in ACEI FDC utilization at approximately twice the cost of ACEIs in recent years. Alongside this, we noted considerable differences in expenditure/DDD for different ACEIs. CONCLUSION & FUTURE PERSPECTIVE: High patient copayments for ARBs appreciably limited their utilization in Serbia, which mirrors the findings from other studies. Potential future measures to enhance prescribing efficiency include reference pricing for ACEIs based on the lowest price of an established ACEI. In addition, reference pricing for FDCs should be based on the reference price of the individual components combined. This builds on recent reforms restricting the reimbursement of FDCs until 3 months after individual components have been prescribed separately. PMID- 24236476 TI - The global landscape of stem cell clinical trials. AB - AIM: To provide a comprehensive analysis of clinical trials (CTs) listed in worldwide registries involving new applications for stem cell-based treatments and account for the role of industry. MATERIALS & METHODS: We developed a data set of 4749 stem cell CTs up to 2013 in worldwide registries. We defined 1058 novel CTs (i.e., trials that were not observational in nature; did not involve an established stem cell therapy for an established indication, such as hematopoietic stem cells for leukemia; and did not investigate supportive measures). Based on trial descriptions, we manually coded these for eight additional elements. RESULTS: Our analysis details the characteristics of novel stem cell CTs (e.g., stem cell types being tested, disease being targeted, and whether interventions were autologous or allogeneic), geotemporal trends, and private sector involvement as sponsor or collaborator. CONCLUSION: The field is progressing at a steady pace with emerging business models for stem cell therapeutics. However, therapeutic rhetoric must be tempered to reflect current clinical and research realities. PMID- 24236475 TI - Nanoliposomes protect against AL amyloid light chain protein-induced endothelial injury. AB - CONTEXT: A newly-recognized pathogenic mechanism underlying light chain amyloidosis (AL) involves endothelial dysfunction and cell injury caused by misfolded light chain proteins (LC). Nanoliposomes (NL) are artificial phospholipid vesicles that could attach to misfolded proteins and reduce tissue injury. OBJECTIVE: To test whether co-treatment with NL reduces LC-induced endothelial dysfunction and cell death. METHODS: Abdominal subcutaneous adipose arterioles from 14 non-AL subjects were cannulated; dilator response to acetylcholine and papaverine were measured at baseline and following 1-hour exposure to LC (20 ug/mL, 2 purified from AL subjects' urine, 1 from human recombinant LC [AL-09]) +/- NL (phosphatidylcholine/cholesterol/phosphatidic acid 70/25/5 molar ratio) or NL alone. Human aortic artery endothelial cells (HAEC) were exposed to Oregon Green-labeled LC +/- NL for 24 hours and intracellular LC and apoptosis (Hoechst stain) were measured. Circular dichroism spectroscopy was performed on AL-09 LC +/- NL to follow changes in secondary structure and protein thermal stability. RESULTS: LC caused impaired dilation to acetylcholine that was restored by NL (control - 94.0 +/- 1.8%, LC - 65.0 +/- 7.1%, LC + NL - 95.3 +/- 1.8%, p <= 0.001 LC versus control or LC + NL). NL protection was inhibited by L NG-nitroarginine methyl ester. NL increased the beta sheet structure of LC, reduced endothelial cell internalization of LC and protected against LC-induced endothelial cell death. CONCLUSIONS: LC induced human adipose arteriole endothelial dysfunction and endothelial cell death, which were reversed by co treatment with NL. This protection may partly be due to enhancing LC protein structure and reducing LC internalization. Nanoliposomes represent a promising new class of agents to ameliorate tissue injury from protein misfolding diseases such as AL. PMID- 24236477 TI - Maternal hyperglycemia according to IADPSG criteria as a predictor of perinatal complications in women with gestational diabetes: a retrospective observational study. AB - OBJECTIVE: We investigated the association between abnormal maternal glucose levels according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and perinatal complications. MATERIALS AND METHODS: Retrospective observational study of data of 492 women in singleton pregnancy and gestational diabetes (GDM) diagnosed according to WHO criteria. Perinatal outcome and maternal characteristics were compared between normo- and hyperglycemic patients using IADPSG criteria and odds ratios calculated for particular outcomes. RESULTS: Maternal fasting hyperglycemia (>=5.1 mmol/L) was associated with significantly higher proportion of birth weight >= 4000 g (19.3% versus 9.7%, p = 0.004, OR: 2.2; 95% CI: 1.3-3.8), gestational insulin therapy (27.7% versus 9.1%, p < 0.001, OR: 3.8; 95% CI: 2.3-6.5), poor long-term metabolic control (HbA1c at diagnosis >= 6.5% [48 mmol/mol]: 19.9% versus 4.6%, p < 0.001, OR: 5.2; 95% CI: 2.5-10.9). Pre-pregnancy obesity (BMI >= 30 kg/m(2), 26.0% versus 11.9%, p < 0.001, OR: 2.6; 95% CI: 1.6-4.3) and positive family history of diabetes (45.2% versus 30.8%, p < 0.002, OR: 1.8; 95% CI: 1.3-2.7) was more frequent in women with fasting hyperglycemia. Two-hour post-load hyperglycemia was only associated with increased prevalence of gestational hypertension (5.1% versus 11.4%, p = 0.046). CONCLUSIONS: Women with fasting but not 2-h hyperglycemia according to IADPSG criteria are at significantly elevated risk of perinatal complications. PMID- 24236478 TI - Assessment of genomic damage and repair on human lymphocytes by paint thinner in vitro. AB - Paint thinners are organic-solvent complex mixtures frequently used by car painters around the world in industries and shops. Some studies have revealed the oxidative effect induced by thinner inhalation; however, its genotoxic effect is poorly studied. The aim of this study was to assess the cytotoxicity, genomic damage and DNA repair in vitro induced by commercial paint thinner 0.14 in human lymphocytes. Cytotoxicity was determined by cell-viability analysis with trypan blue after 4 h treatment with different thinner concentrations (0.025 to 1.2 uL/mL). Genomic damage was evaluated by means of the alkaline single-cell gel electrophoresis (SCGE; pH > 13) in treated cultures after 1 h with three low cytotoxic thinner concentrations (0.05, 0.1 and 0.2 uL/mL). In order to evaluate the genomic DNA repair, one set of SCGE slides was prepared immediately after treatment, and another one was prepared after 4 h of liquid-holding recovery. A significant level of cytotoxicity was observed over the entire concentration range of paint thinner in lymphocytes (F = 175.98; p <= 0.001). In the SCGE % tail DNA assessment, a significant increase of lymphocyte genomic damage was evidenced (F = 72.32; p < 0.001). In addition, we found a significant decrease in the % tail DNA in thinner-treated cells after liquid-holding recovery period (all p < 0.05), demonstrating that DNA primary lesions induced by low-cytotoxic thinner concentrations are efficiently repaired. In conclusion, thinner components induce cytotoxicity and genomic damage in human lymphocytes under the study conditions, possibly by oxidative and alkylative DNA damage. PMID- 24236479 TI - Overlapping effects of genetic variation and epigenetics on drug response: challenges of pharmacoepigenomics. PMID- 24236480 TI - Novel nonsynonymous variants associated with blood pressure control in response to antihypertensives and their impact on cardiovascular outcomes. PMID- 24236481 TI - Genetic scoring to predict antihypertensive drug response using gene variants associated with hypertension. PMID- 24236482 TI - Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. AB - AIM: This preliminary study investigated genomic biomarkers for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), related to three antiepileptic drugs, zonisamide, phenobarbital and phenytoin. PATIENTS & METHODS: HLA class I and HLA-DRB1 loci were genotyped for Japanese patients with zonisamide-, phenobarbital- or phenytoin-induced SJS/TEN (n = 12, 8 and 9, respectively) and for healthy Japanese volunteers (n = 2878). RESULTS: Carrier frequencies of HLA-A*02:07 in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively. Carrier frequencies of HLA-B*51:01 in patients with phenobarbital- and phenytoin-induced SJS/TEN and in controls were 75.0, 55.6 and 15.2%, respectively. HLA-A*02:07 and HLA-B*51:01, in a dominant model, were significantly associated with zonisamide- and phenobarbital-induced SJS/TEN, respectively (Pc = 0.0176 and 0.0042, respectively). CONCLUSION: Our data suggest that HLA-A*02:07 and HLA-B*51:01 are potential biomarkers for zonisamide- and phenobarbital-induced SJS/TEN, respectively, in Japanese individuals. PMID- 24236484 TI - Gene-wide tagging study of the effects of common genetic polymorphisms in the alpha subunits of the GABA(A) receptor on epilepsy treatment response. AB - AIM: We aimed to identify the effect of SNPs in the alpha-subunits of GABAA receptors on epilepsy treatment outcomes by using a gene-wide tagging method. MATERIALS & METHODS: There were 720 epileptic patients included in the present study. A total of 136 tagging SNPs in GABRA1, GABRA2, GABRA3, GABRA4, GABRA5 and GABRA6 were genotyped by Illumina((r))GoldenGate((r)) Genotyping platform. Clinical information, such as prescribed antiepileptic drugs, height, weight, epilepsy syndrome classification, etiology, number of attacks, renal function and liver function were collected. The associations between SNPs and epilepsy treatment outcomes were analyzed using SAS((r)) version 9.1.3. Both multivariate logistic regression and multifactor dimensionality reduction analyses were performed. RESULTS: The results of single gene effects did not remain significant after Bonferroni's corrections. Further multivariate logistic regression and multifactor dimensionality reduction analyses of interactions between these genes showed that under adjustment of clinical factors, the epilepsy treatment outcomes were significantly associated with the genotype combinations of GABRA1 rs6883877, GABRA2 rs511310 and GABRA3 rs4828696 (p < 0.0001; adjusted r(2) = 0.149). CONCLUSION: Our results indicated that genetic variants in the alpha subunits of GABA(A) receptors may interactively affect the treatment responses of antiepileptic drugs. Further replication using an independent sample collection would be essential to confirm our findings. PMID- 24236483 TI - Issues surrounding the health economic evaluation of genomic technologies. AB - AIM: Genomic interventions could enable improved disease stratification and individually tailored therapies. However, they have had a limited impact on clinical practice to date due to a lack of evidence, particularly economic evidence. This is partly because health economists are yet to reach consensus on whether existing methods are sufficient to evaluate genomic technologies. As different approaches may produce conflicting adoption decisions, clarification is urgently required. This article summarizes the methodological issues associated with conducting economic evaluations of genomic interventions. MATERIALS & METHODS: A structured literature review was conducted to identify references that considered the methodological challenges faced when conducting economic evaluations of genomic interventions. RESULTS: Methodological challenges related to the analytical approach included the choice of comparator, perspective and timeframe. Challenges in costing centered around the need to collect a broad range of costs, frequently, in a data-limited environment. Measuring outcomes is problematic as standard measures have limited applicability, however, alternative metrics (e.g., personal utility) are underdeveloped and alternative approaches (e.g., cost-benefit analysis) underused. Effectiveness data quality is weak and challenging to incorporate into standard economic analyses, while little is known about patient and clinician behavior in this context. Comprehensive value of information analyses are likely to be helpful. CONCLUSION: Economic evaluations of genomic technologies present a particular challenge for health economists. New methods may be required to resolve these issues, but the evidence to justify alternative approaches is yet to be produced. This should be the focus of future work in this field. PMID- 24236485 TI - Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations. AB - AIM: Acute urticaria/angioedema (AUA) induced by cross-intolerance to NSAIDs is the most frequent clinical entity in hypersensitivity reactions to drugs. In this work, we conducted a genome-wide association study in Spanish and Han Chinese patients suffering from NSAID-induced AUA. MATERIALS & METHODS: A whole-genome scan was performed on a total of 232 cases (112 Spanish and 120 Han Chinese) with NSAID-induced AUA and 225 unrelated controls (124 Spanish and 101 Han Chinese). RESULTS: Although no polymorphism reached genome-wide significance, we obtained suggestive associations for three clusters in the Spanish group (RIMS1, BICC1 and RAD51L 1) and one region in the Han Chinese population (ABI3BP). Five regions showed suggestive associations after meta-analysis: HLF, RAD51L1, COL24A1, GalNAc T13 and FBXL7. A majority of these genes are related to Ca(2+), cAMP and/or P53 signaling pathways. CONCLUSION: The associations described were different from those related to the metabolism of arachidonic acid and could provide new mechanisms underlying NSAID-induced AUA. PMID- 24236487 TI - Fruit flies as a powerful model to drive or validate pain genomics efforts. AB - Chronic pain is a disabling condition that persists even after normal healing processes are complete and presents considerable physical, psychological and financial burdens for patients globally. However, current analgesic treatments do not meet clinical needs. Here, we review genomic and pharmacogenomic studies of pain in humans and nociception in the fruit fly Drosophila melanogaster, and provide evidence supporting the use of fly genetics to compliment genome-wide and pharmacogenomic studies of human conditions, such as pain. Combining genomic and pharmacogenomic techniques to study chronic pain in humans with functional genomic assessment in model organisms may provide molecular rationale for developing more personalized or improving generalized chronic pain therapies. PMID- 24236486 TI - Variability in histamine receptor genes HRH1, HRH2 and HRH4 in patients with hypersensitivity to NSAIDs. AB - AIM: Histamine plays an important role in the pathogenesis of allergic diseases. Genetic variations in histamine receptors (HRH) may influence the expression of allergic diseases. This study analyzes the association between HRH variants and NSAID hypersensitivity reactions. PATIENTS & METHODS: The authors analyzed copy number variations (CNVs) and common functional SNPs in genes HRH1, HRH2 and HRH4 in 442 unrelated patients with hypersensitivity to NSAIDs and in 414 healthy unrelated controls. RESULTS: The authors identified, both in patients and control subjects, individuals carrying CNVs in HRH genes. The most common genotype corresponded to two copies of each gene, but carriers of one or three copies of HRH1 (5% of individuals), HRH2 (1.1%) and HRH4 genes (0.9%) were also identified. CONCLUSION: For the first time, we describe CNVs in human HRH genes. Neither common functional SNPs in HRH genes nor CNVs influenced the risk of developing hypersensitivity to NSAIDs. PMID- 24236488 TI - Pediatric perspective on pharmacogenomics. AB - The advances in high-throughput genomic technologies have improved the understanding of disease pathophysiology and have allowed a better characterization of drug response and toxicity based on individual genetic make up. Pharmacogenomics is being recognized as a valid approach used to identify patients who are more likely to respond to medication, or those in whom there is a high probability of developing severe adverse drug reactions. An increasing number of pharmacogenomic studies are being published, most include only adults. A few studies have shown the impact of pharmacogenomics in pediatrics, highlighting a key difference between children and adults, which is the contribution of developmental changes to therapeutic responses across different age groups. This review focuses on pharmacogenomic research in pediatrics, providing examples from common pediatric conditions and emphasizing their developmental context. PMID- 24236489 TI - Opening Pandora's box in the UK: a hypothetical pharmacogenetic test for clozapine. AB - Clozapine is a uniquely efficacious antipsychotic drug in treatment-resistant schizophrenia. Its use is restricted due to adverse effects including a rare but dangerous reduction in neutrophils (agranulocytosis) and the mandatory hematological monitoring this entails in many countries. We review the statistical, ethical and legal issues arising from a hypothetical pharmacogenetic test for clozapine, using the UK as an exemplary case for consideration. Our key findings include: a consideration of the probabilistic results that a pharmacogenetic test may return; the impact on drug licensing; and the potential for pharmacogenetic tests for clozapine being used without consent under the UK's legal framework. We make recommendations regarding regulatory changes applicable to the special case of pharmacogenetic testing in clozapine treatment. PMID- 24236490 TI - u-opioid receptor gene variant OPRM1 118 A>G: a summary of its molecular and clinical consequences for pain. AB - The human u-opioid receptor variant 118 A>G (rs1799971) has become one of the most analyzed genetic variants in the pain field. At the molecular level, the variant reduces opioid receptor signaling efficiency and expression, the latter probably via a genetic-epigenetic interaction. In experimental settings, the variant was reproducibly associated with decreased effects of exogenous opioids. However, this translates into very small clinical effects (meta-analysis of 14 studies: Cohen's d = 0.096; p = 0.008), consisting of slightly higher opioid dosing requirements in peri- and post-operative settings. An effect can neither be maintained for chronic analgesic therapy nor for opioid side effects. It seems unlikely that further studies will reveal larger effect sizes and, therefore, further analyses appear unwarranted. Thus, due to its small effect size, the SNP is without major clinical relevance as a solitary variant, but should be regarded as a part of complex genotypes underlying pain and analgesia. PMID- 24236492 TI - Isolation and identification of flavonoids from Coreopsis lanceolata L. petals. AB - The methanol extract of Coreopsis lanceolata L. petals was acid-hydrolysed, and 7,3',4'-trihydroxy-8-methoxyflavanone (1) and 6,3',4'-trihydroxy-7-methoxyaurone (leptosidin) (2) were successfully isolated. The structure of compound 1 is designated to flavanone based on X-ray crystallographic analysis and NMR spectroscopic analysis. Compound 1 showed high-antioxidant effects based on diphenylpicrylhydrazyl radical scavenging assay (94.3% scavenging rate) and superoxide dismutase-like activity assay (23.9% inhibition rate). PMID- 24236493 TI - Finally! The structural secrets of a HD-GYP phosphodiesterase revealed. AB - The major sessility-motility lifestyle change and additional fundamental aspects of bacterial physiology, behaviour and morphology are regulated by the secondary messenger cyclic di-GMP (c-di-GMP). Although the c-di-GMP metabolizing enzymes and many receptors have been readily characterized upon discovery, the HD-GYP domain c-di-GMP phosphodiesterase family remained underinvestigated. In this issue of Molecular Microbiology, Bellini et al. provide an important step towards functional and structural characterization of the previously neglected HD-GYP domain family by resolving the crystal structure of PmGH, a catalytically active family member from the thermophilic bacterium Persephonella marina. The crystal structure revealed a novel tri-nuclear catalytic iron centre involved in c-di-GMP binding and catalysis and provides the structural basis to subsequently characterize in detail the catalytic mechanism of hydrolysis of c-di-GMP to GMP by HD-GYP domains. PMID- 24236494 TI - A life-course perspective on stigma-handling: resilience in persons of restricted growth narrated in life histories. AB - PURPOSE: The aim of the study is to explore how personal and contextual experiences throughout the life course are recollected as having influenced the development of stigma-handling strategies among people associated with disability and stigma. The article describes the development of stigma handling among ageing persons of restricted growth in order to avert negative effects, develop resilience, strengthen the self and support a positive identity. METHOD: Qualitative retrospective interviews were conducted with ten persons - seven women and three men aged between 45 and 65 years - of short stature. Their narratives are analysed from a life-course perspective and the results presented under two main themes: the development of strategies during different stages of life, and the use of general non-stage-bound strategies. RESULTS: The study shows how stigma-handling has evolved from childhood to become, by adult years, refined, contextualised strategies demonstrating human resilience. The analysis documents the impact of human agency on personal lives and the subjects' efforts and strengths in handling adversity. CONCLUSION: The results demonstrate how the "insider perspective" reveals the individual's resources, resilience and strategies and provides an important perspective for the rehabilitation setting. Implications for Rehabilitation The study document human agency, resilience and strength in a life course perspective among people of restricted growth faced with stigmatization. The efforts and stigma handling strategies developed during the life course, such as withdrawal, humour, ignoring and positive thinking, are important tools to be recognized with relevance for other patient groups. The "insider perspective" revealing the potentialities and strength of human agency and resilience, should be further explored within the field of rehabilitation. PMID- 24236495 TI - Comparison of three instruments to assess changes of motor impairment in acute hemispheric stroke: the Stroke Impairment Assessment Set (SIAS), the National Institute of Health Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS). AB - PURPOSE: The purpose was to compare the performance of three representative instruments to measure changes of motor recovery with acute hemispheric stroke. METHOD: In 41 consecutive patients with acute hemispheric infarction, motor recovery was assessed within 3 days of onset and then every 2 weeks until the 12th week with the Stroke Impairment Assessment Set (SIAS), the National Institutes of Health stroke scale (NIHSS) and the Canadian Neurological Scale (CNS). We analyzed the relationships among the corresponding subscales of the three instruments with the Spearman's rank correlation method, and compared their responsiveness by plotting the temporal profiles of scores of each instrument and by testing the significance of changes over time with the Friedman test. RESULTS: High correlations were observed among the three instruments at each examination point. However, the SIAS scores were more widely dispersed at the same NIHSS and CNS scores. Friedman test revealed that the scores changed significantly during the observation period with the SIAS and the CNS but not with the NIHSS. The changes were detected later with the CNS than with the SIAS. CONCLUSIONS: Although the assessment results with the three instruments were highly inter correlated, the SIAS performed better with respect to responsiveness to changes. Implication for Rehabilitation When providing rehabilitation services to patients with stroke, it is important to document objectively the level of their impairment from the acute stage and during the entire course of rehabilitation with standardized instrument, and to predict their functional outcomes as early and accurately as possible. This study therefore compared three representative instruments with established psychometric properties, the SIAS, the NIHSS and the CNS, with respect to their ability to document motor impairment and their responsiveness to recovery in patients with acute hemispheric stroke. PMID- 24236496 TI - Prevalence of joint contractures and muscle weakness in people with multiple sclerosis. AB - OBJECTIVES: To investigate the prevalence of joint contracture (limited passive range of joint motion) and muscle weakness in a population with multiple sclerosis (MS). A secondary aim was to establish normative data of functional tests of mobility and balance of people with MS who are still ambulant. DESIGN: Cross-sectional study. SETTING: People with MS living in metropolitan Sydney, Australia. PARTICIPANTS: 330 people with MS living in metropolitan Sydney, Australia were randomly sampled on 23 July 2009 from the MS Australia register and invited to participate. MAIN OUTCOME MEASURES: Passive range of motion of large joints of the limbs and muscle strength. Tests of walking and balance were also conducted. RESULTS: 156 people (109 females, 47 males; mean age 54.2 years; mean time since diagnosis 14.9 years) agreed to participate and were assessed. Fifty-six per cent (56%) of participants had contracture in at least one major joint of upper or lower limb. The most common site of contracture was the ankle (43.9%). Seventy per cent (70%) of participants had muscle weakness in one or more muscle groups. As muscle weakness, joint contractures were present at early stage of MS and the prevalence was associated with the progression of the disease. CONCLUSIONS: These data show that in addition to muscle weakness joint contractures are highly prevalent among people with MS, especially in the ankle joint. This implicates that prevention of contracture is crucial in providing rehabilitation to people with MS. PMID- 24236497 TI - Life situation of adults with congenital limb reduction deficiency in Sweden. AB - PURPOSE: To describe the current life situation of adults with congenital limb reduction deficiencies (CLRD), living in Sweden, regarding their main daily occupation, leisure activities and self-reported general health. METHODS: A cross sectional survey was conducted using a study-specific questionnaire, sent by post. Hundred and seventeen persons with different extent, forms and levels of CLRD (mean age 33 years) responded to the questionnaire. RESULTS: Work or study was the main occupation for 86% of the participants and 50% had completed a college or university education. About 7% were unemployed and 3% were on sick leave. The participants were highly involved in social and physical activities during leisure time. The majority reported good or very good general health. CONCLUSION: This study is the first investigation of the life situation of adults with CLRD described with a perspective from Swedish society. The participants were educated and worked to a great extent, which corresponds well to the Swedish population as a whole. Further research is needed, especially with a focus on the internal perspective of life situation, different aspects of work capacity, occurences of strain injuries and the benefit of assistive devices among adults with CLRD. Implications for Rehabilitation People with CLRD require a health care system with a multi-professional rehabilitation team offering regular contact during their life time. Educational system offering study counselling on all education levels (from primary school to university) is an important type of support for people with any kind of deficiency, in order to find suitable education and profession. Work is of importance for an acceptable life situation. Rehabilitation for people with CLRD should emphasise facilitating their ability to work, through engagement in individual personal capacity and self-efficacy. The majority of people with CLRD are users of prostheses and assistive devices. The benefits of the devices are basic but the rehabilitation should also include aspects of usability and use worthiness for individuals in performing their daily activities. PMID- 24236498 TI - Alkene oxyalkylation enabled by merging rhenium catalysis with hypervalent iodine(III) reagents via decarboxylation. AB - Rhenium-catalyzed oxyalkylation of alkenes is described, where hypervalent iodine(III) reagents derived from widely occurring aliphatic carboxylic acids were used as, for the first time, not only an oxygenation source but also an alkylation source via decarboxylation. The reaction also features a wide substrate scope, totally regiospecific difunctionalization, mild reaction conditions, and ready availability of both substrates. Mechanistic studies revealed a decarboxylation/radical-addition/cation-trapping cascade operating in the reaction. PMID- 24236499 TI - Phase diagrams and solvate structures of binary mixtures of glymes and Na salts. AB - We prepared a series of binary mixtures composed of selected Na salts and glymes (tetraglyme, G4, and pentaglyme, G5) with different salt concentrations and anionic species ([X](-): [N(SO2CF3)2](-) = [TFSA](-), [N(SO2F)2](-) = [FSA](-), ClO4(-), PF6(-)) and studied the effects of concentration, anionic structure, and glyme chain length on their phase diagrams and solvate structures. The phase diagrams clearly illustrate that all the mixtures form 1:1 complexes, [Na(G4 or G5)1][X]. The thermal stability of the equimolar mixtures was drastically improved in comparison with those of diluted systems, indicating that all the glyme molecules coordinate to Na(+) cations to form equimolar complexes. Single crystal X-ray crystallography revealed that [Na(G5)1][X] forms characteristic solvate structures in the crystalline state irrespective of the paired anion species. A comparison of the solvate structures of the glyme-Na complexes with those of the glyme-Li complexes suggests that the ionic radii of the coordinated alkali-metal cations have substantial effects on the resulting solvate structures. The Raman bands of the complex cations were assigned by quantum chemical calculations. Concentration dependencies of cationic and anionic Raman spectra show good agreement with the corresponding phase diagrams. In addition, the Raman spectra of the 1:1 complexes strongly suggest that the glymes coordinate to Na(+) cation in the same way in both liquid and crystalline states. However, the aggregated structure in the crystalline state is broken by melting, which is accompanied by a change in the anion coordination. PMID- 24236501 TI - Commentary: Adult-born neurons with unique GABAergic synapses. PMID- 24236500 TI - Construction and evaluation of a self rating scale for stress-induced exhaustion disorder, the Karolinska Exhaustion Disorder Scale. AB - Prolonged stress (>= six months) may cause a condition which has been named exhaustion disorder (ED) with ICD-10 code F43.8. ED is characterised by exhaustion, cognitive problems, poor sleep and reduced tolerance to further stress. ED can cause long term disability and depressive symptoms may develop. The aim was to construct and evaluate a self-rating scale, the Karolinska Exhaustion Disorder Scale (KEDS), for the assessment of ED symptoms. A second aim was to examine the relationship between self-rated symptoms of ED, depression, and anxiety using KEDS and the Hospital Anxiety and Depression Scale (HAD). Items were selected based on their correspondence to criteria for ED as formulated by the Swedish National Board of Health and Welfare (NBHW), with seven response alternatives in a Likert-format. Self-ratings performed by 317 clinically assessed participants were used to analyse the scale's psychometric properties. KEDS consists of nine items with a scale range of 0-54. Receiver operating characteristics analysis demonstrated that a cut-off score of 19 was accompanied by high sensitivity and specificity (each above 95%) in the discrimination between healthy subjects and patients with ED. Reliability was satisfactory and confirmatory factor analysis revealed that ED, depression and anxiety are best regarded as different phenomena. KEDS may be a useful tool in the assessment of symptoms of Exhaustion Disorder in clinical as well as research settings. There is evidence that the symptom clusters of ED, anxiety and depression, respectively, reflect three different underlying dimensions. PMID- 24236502 TI - A case of Bjornstad syndrome caused by novel compound heterozygous mutations in the BCS1L gene. PMID- 24236503 TI - An inorganic chromophore based on a molecular oxide supported metal carbonyl cluster: [P2W17O61{Re(CO)3}3{ORb(H2O)}(MU3-OH)]9-. AB - A polyoxometalate-supported trirhenium carbonyl cluster, mimicking metal oxide supported interfacial dyadic structures, has been synthesized and characterized. Multiple techniques, including computational and transient absorption spectroscopy, have been applied to characterize the charge-transfer dynamics occurring at the interfaces of this "double cluster". The stepwise kinetics of charge separation and recombination has been thoroughly investigated. PMID- 24236504 TI - Opening the black box: outcomes of interactions between arbuscular mycorrhizal (AM) and non-host genotypes of Medicago depend on fungal identity, interplay between P uptake pathways and external P supply. AB - We investigated the physiology that underlies the influence of arbuscular mycorrhizal (AM) colonization on outcomes of interactions between plants. We grew Medicago truncatula A17 and its AM-defective mutant dmi1 in intragenotypic (two plants per pot of the same genotype, x2) or intergenotypic (one plant of each genotype, 1 + 1) combinations, inoculated or not with Rhizophagus irregularis (formerly Glomus intraradices) or Gigaspora margarita. We measured plant growth, colonization, contributions of AM and direct P uptake pathways using (32)P, and expression of plant Pi transporter genes at two levels of P supply. A17 (x2) responded positively to inoculation only at low P. The response was enhanced with 1 + 1 even at high P where colonization in A17 was reduced. With R. irregularis P uptake by the AM pathway was unaffected by P supply, whereas with G. margarita, the AM pathway was lower at high P, and direct uptake higher. Gene expression varied and was unrelated to P uptake through the two pathways. There was no evidence of plant control of P uptake via R. irregularis at high P but there was via G. margarita. Importantly, growth responses of plant genotypes grown alone did not predict outcomes of intergenotypic interactions. PMID- 24236505 TI - Proline-catalyzed asymmetric synthesis of syn- and anti-1,3-diamines. AB - A general organocatalytic strategy for asymmetric synthesis of both syn/anti-1,3 diamines has been developed. The strategy employs proline-catalyzed sequential alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step where syn-1,3-diamine was obtained as the most favorable product. PMID- 24236506 TI - Probing interfacial interactions using core-satellite plasmon rulers. AB - Understanding molecular interactions at the interfaces of nanoparticles is fundamentally important because they determine the stability, affinity, functionality, and assembly of nanoparticles. However, probing the governing intermolecular forces at the interfaces, particularly for the nanoparticles dispersed in solution, remains challenging. Here, we demonstrate that the interfacial interactions between citrate-capped gold nanoparticles and various molecular functional groups can be probed using a plasmon ruler, based on a well defined core-satellite nanoassembly structure. Different nature of the interactions causes a subtle change in the interparticle distance, and the change is sensitively measured as a shift in the plasmon coupling band of the core satellite nanoassemblies. Molecular interactions including covalent bonding, hydrogen bonding, electrostatic interactions, and van der Waals interactions are explored. PMID- 24236507 TI - Human health and transgenic crops symposium introduction. PMID- 24236508 TI - Discrepancies among three laboratory methods for Clostridium difficile detection and a proposal for their optimal use. AB - Clostridium difficile is the major cause of nosocomial diarrhoea. Several detection methods are available for the laboratory diagnosis of C. difficile, but these vary in terms of sensitivity and specificity. In this study, we compared the performance of three following laboratory tests to detect C. difficile: in house real-time PCR aiming for toxin B gene (tcdB), EIA for detection of toxins A and B (Premier Toxins A & B) and C. difficile culture in selective medium (bioMerieux). Our results were grouped into three categories as follows: (1) C. difficile-associated diarrhoea (CDAD); (2) asymptomatic carriers; and (3) negative results. Among the 113 patients included in the study, 9 (8.0%) were classified as CDAD, 19 (16.8%) were asymptomatic carriers, 76 (67.2%) had negative results and 9 (8.0%) could not be categorized (positive test for C. difficile toxins only). PCR was found to be the most sensitive diagnostic test in our study, with the potential to be used as a screening method for C. difficile colonization/CDAD. Diagnosis of CDAD would be better performed by a combination of PCR and EIA tests. PMID- 24236509 TI - Healthcare cost impact of biological drugs compared with traditional systemic treatments in psoriasis: a cohort analysis in the French insurance database. AB - BACKGROUND: Biological drugs have dramatically improved the management of moderate to severe psoriasis. Little is known about their economic impact in daily clinical practice. OBJECTIVE: The aim of this study was to estimate the costs of biological drugs, in term of health resources consumption, and to compare it with costs induced by traditional systemic treatments. METHODS: This cohort study was built from the French health insurance database in the Midi Pyrenees area (2.8 million inhabitants, South West of France). We compared health care costs between 'exposed' patients treated with biological drugs (adalimumab, etanercept, infliximab or ustekinumab) and 'unexposed' patients defined as patients who received traditional systemic treatments (phototherapy, acitretin, methotrexate or cyclosporin) during a 6-month period. RESULTS: A total of 1924 patients met the inclusion criteria. Sixty-nine patients were 'exposed', whereas 1855 patients were 'unexposed'. 'Exposed' patients had a mean total healthcare cost of 8107? vs. 1678? (P < 0.001) for 'unexposed' patients. They had higher costs concerning inpatient admission, medication and consultations including dermatology consultations, laboratory, non-medical care and transportation. Biological drug prescription was associated with an increase in the use of anti infective drugs and with a reduction in the use of psychoactive drugs. CONCLUSION: The mean total health care expenditure in patients treated with biological drugs was five times higher as compared with patients treated with traditional systemic treatments. The limitation of the study is the short duration of follow-up comprising a loading dose period for some biological drugs. This may have contributed to an overestimation of drug-related costs. PMID- 24236510 TI - N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD. AB - The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri , providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is composed of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g., deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. Although the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study because of the hydrophobic nature of the IpaB and IpaC translocator proteins. Here, we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11-27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together, these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation. PMID- 24236511 TI - Influence of immunohistochemistry on the final diagnosis of breast biopsies. AB - AIMS: Because of the introduction of mammography screening programmes in Europe, the number of breast biopsies performed is increasing. We investigated the influence of immunohistochemistry (IHC) on the final diagnosis of breast biopsies by comparing the primary diagnoses (based on the results of haematoxylin and eosin staining only) with the final diagnoses (based on the additional information provided by IHC). METHODS AND RESULTS: We analysed the breast biopsies which were performed at the University of Halle-Wittenberg between 2006 and 2010 and for which the pathologist requested IHC for making the final diagnosis. According to the B-categorization scheme, the primary diagnosis changed in 37 of a total of 429 biopsies (8.6%). In 18 of these biopsies (48.6%) the category changed from B1-B2 to B3-B5 or vice versa, which would imply a different work-up. Only 77% of the primary diagnoses of breast cancer in situ were confirmed. CONCLUSION: IHC has a considerable influence on the final diagnosis of breast biopsies in several situations, including those in which the biopsied women are at risk of inadequate therapeutic intervention. The influence is particularly notable among those biopsies for which IHC is performed in order to assess the suspicion of breast cancer in situ. PMID- 24236513 TI - Complex questions command complex analyses: comparative effectiveness of drug treatment strategies in atrial fibrillation. PMID- 24236514 TI - European collaboration on relative effectiveness will move into the next phase. PMID- 24236515 TI - Comparative effectiveness research in liver transplantation: crossing the cost and quality chasm. PMID- 24236517 TI - From methods to policy: Quantifying the impact of comparative effectiveness research: let us avoid the mistakes of the past. PMID- 24236518 TI - Data acquisition, tumor heterogeneity and precision medicine: future challenges for oncologic comparative effectiveness research. PMID- 24236519 TI - Use of relative effectiveness information in reimbursement and pricing decisions in Europe. AB - Although comparative effectiveness has received considerable attention recently - especially in the USA - it is not a new concept. In Europe, it has been applied for some time now in the pricing and reimbursement processes of many countries. Each one uses it in its own way, however, with variations in the precise definition and the role it plays in the process. It remains to be seen whether the implementation of comparative effectiveness becomes more harmonized and whether it will be integrated better with the registration process. Regardless of the extent to which it is standardized, obtaining the data will remain a substantial hurdle, both methodologically and operationally. Everyone wants comparative effectiveness information but no one knows quite how to make it happen. PMID- 24236520 TI - Comparative effectiveness research in spine surgery. AB - Degenerative spine disorders are a significant cause of patient morbidity and are a prominent factor in healthcare costs in many countries. Pressure for healthcare cost control and the desire for improved outcomes have led to an expanding emphasis on evidence-based medicine methodologies in spine research. Determination of the optimal treatment paradigm for many common degenerative spinal disorders has proven difficult and comparative effectiveness research is increasingly being employed to examine these clinical dilemmas. The Swedish Spine Registry and the Registry of the Scoliosis Research Society are two of the long standing databases compiling data for spine patients. Spine surgery professional organizations have recently taken a prominent role in assembling procedural- and diagnosis-based registries, specifically addressing therapeutic outcomes for spine patients. As healthcare systems continue to evolve, comparative effectiveness research driven by spine registries may better elucidate the appropriate clinical choices for patients with these challenging illnesses. PMID- 24236521 TI - Pros and cons of pragmatic clinical trials. AB - Traditional randomized controlled trials are the 'gold standard' for evaluating health interventions and are typically designed to maximize internal validity, often at the cost of limited generalizability. Pragmatic randomized controlled trials should be designed with a conscious effort to generate evidence with a greater external validity by making the research question as similar as possible to the questions faced by clinical decision-makers (i.e., patients and their families, physicians, policy makers and administrators) and then answer that question with rigor. Clarity and transparency about the specifics of the research question are the keys to designing, as well as interpreting, any clinical trial. PMID- 24236522 TI - Matching study designs to disability-related comparative effectiveness research questions. AB - Comparative effectiveness research can help patients with disabilities; their caregivers and providers determine which healthcare choices are beneficial and will most reduce limitations and barriers, and improve quality of life. Well designed comparative effectiveness research will be critical as the number of working-age adults affected by disability grows in the future, along with disability-related health expenditures. To better address the need for high quality and informative research on the effectiveness of interventions for people with disabilities, the authors conducted a comprehensive review of existing standards for assessing evidence quality, collecting input from a wide range of experts and policy makers to determine the type of evidence needed for informing disability-related decision-making and the applicability of existing standards to disability research. This review article presents methodological and design issues for researchers to consider when addressing disability-related comparative effectiveness research questions. PMID- 24236523 TI - Incidence of skeletal morbidity rates over time in patients with multiple myeloma related bone disease as reported in randomized trials employing bone-modifying agents. AB - AIM: The purpose of this review was to investigate if advances in bone-targeted therapies have decreased the incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease. METHODS: A literature search was conducted over the OvidSP platform in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify Phase III results from bone-targeted therapy trials in patients with multiple myeloma. The skeletal morbidity rate was the end point of interest, and for each study, a mean year of enrollment ([start of enrollment + end of enrollment]/2) was calculated. RESULTS: A total of eight study arms were identified, with only two placebo arms; therefore, a weighted linear regression was not feasible and only intervention treatment arms were analyzed. A statistically significant downward trend in the skeletal morbidity rate was observed in all intervention arms. CONCLUSION: The incidence of skeletal morbidity rates has decreased significantly over time in patients with multiple myeloma. PMID- 24236524 TI - Adverse events across generations of bone-modifying agents in patients with solid tumor cancers reported in Phase III randomized trials. AB - AIMS: The objective of this study is to compare adverse events experienced among different bone-modifying agents. METHODS: A literature search was conducted to identify Phase III bisphosphonate and bone-modifying agent trials reporting adverse effects. Thirty-seven adverse events of interest were identified for six different treatment options. Weighted linear regression modeling was performed on the adverse event proportions with treatment groups, normalized through applying natural log transformations. RESULTS: There were significant differences in adverse events of vomiting (p = 0.045) and osteonecrosis of the jaw (p = 0.017), and combined item events of nausea/vomiting (p = 0.048), hematological and lymphatic system toxicities (p = 0.020), and any respiratory system problem (p = 0.023) between bone-modifying agent and placebo trials. The significant toxicities were observed even after adjusting for the two confounding factors of age and primary cancer site. CONCLUSION: While adverse effects are consistently experienced more frequently in patients receiving bone-modifying agents when compared with placebos, we find that the majority of individual side effects are not significantly more frequent in patients receiving bone-modifying agents compared with placebo. PMID- 24236527 TI - Analysis of essential oil constituents of three Dasymaschalon species (Annonaceae) from Vietnam. AB - The compositions of essential oils of the leaves and stem barks of three Vietnamese species of Dasymaschalon J. D. Hooker & Thomson. (Annonaceae) were determined by means of gas chromatography and gas chromatography-mass spectrometry. Dasymaschalon longiusculum (Ban) yielded oils in which the major components were alpha-pinene (28.9% and 12.5%, respectively), beta-pinene (26.5% and 13.3%, respectively), beta-myrcene (12.0% and 6.0%, respectively) for the leaf and stem. The main compounds of the leaf and stem oils of Dasymaschalon glaucum Merr. & Chun. were alpha-pinene (14.4% and 10.5%, respectively), beta pinene (14.4% and 10.3%, respectively) and bicycloelemene (5.2% and 30.0%, respectively). The essential oil of Dasymaschalon robinsonii Jovet-Ast was different, mainly comprising alpha-copaene (12.7% and 16.6%, respectively), germacrene B (11.3% and 7.5%, respectively), delta-cadinene (5.6% and 5.3%, respectively) for the leaf and stem. PMID- 24236526 TI - Diagnostic yield of cytologic analysis of pericardial effusion in dogs. AB - BACKGROUND: Pericardial effusion cytology is believed by many to be of limited value, yet few studies have evaluated its diagnostic utility. OBJECTIVES: To determine the diagnostic utility of cytologic analysis of pericardial effusion in dogs and to determine if consideration of additional data could improve the diagnostic yield. ANIMALS: Two hundred and fifty-nine dogs with cytologic analysis of pericardial effusion performed between April 1990 and June 2012. METHODS: Electronic medical records from a university teaching hospital were retrospectively reviewed; signalment, complete blood count, serum biochemistry, cytologic analysis of pericardial effusion, and echocardiographic data were recorded. Cytology was classified as diagnostic (infectious or neoplastic) or nondiagnostic (hemorrhagic or other) and groups were compared with multiple Student's t-tests. RESULTS: Cytology was grouped as nondiagnostic (92.3%) or diagnostic (7.7%) and characterized as hemorrhagic (90%), neoplastic (4.6%), infectious (3.1%), or other (2.3%). Overall cytologic analysis of pericardial effusion diagnostic utility was 7.7% and increased to 20.3% if the effusion hematocrit (HCT) <10%; echocardiographic evidence of a mass did not result in a significant increase in the diagnostic utility. CONCLUSIONS AND CLINICAL IMPORTANCE: The diagnostic utility of cytologic analysis of canine pericardial effusion is variable depending on the underlying etiology. In this group of dogs, the diagnostic yield of cytologic analysis was greater for pericardial effusion samples in which the HCT was less than 10%. PMID- 24236528 TI - Psychometric validation of the Women's Health Questionnaire in menopausal women. AB - The objective of this study was to adapt the Women's Health Questionnaire (WHQ) to women who speak Turkish and are from the Turkish culture, and to assess the validity and reliability of the Turkish version of the scale. A convenience sample of women undergoing the menopausal transition or in the postmenopausal period was recruited at one primary health care center in Erzurum, Turkey. The researchers selected consecutive women who applied to the center for health care services. Three hundred sixty-six women were asked to participate in the study and to complete the WHQ during their appointment at the health care center in 2010. In the assessment of construct validity, nine factors were identified: depressed mood; menstrual symptoms; somatic symptoms; anxiety/fears; attractiveness; sexual behaviour; vasomotor symptoms; memory; and sleep problems. The nine factors explained 56.5% of the total variance. The overall internal reliability coefficient of this scale was 0.80. Evidence of the validity, reliability, and acceptability of the questionnaire was provided in this study. The Turkish version of the questionnaire is easy to understand and allows evaluation of women's quality of life for various purposes. PMID- 24236529 TI - Design of innovated lipid-based floating beads loaded with an antispasmodic drug: in-vitro and in-vivo evaluation. AB - CONTEXT: Drotaverine hydrochloride (DRT) is used to treat gastrointestinal spasms accompanied with diarrhoea. Hence, the drug suffers from brief residence in the highly moving intestine during diarrhoea which leads to poor bioavailability and frequent dosing. OBJECTIVE: This study aimed to extend DRT residence in the stomach. METHODS: Calcium alginate floating beads were prepared using sodium alginate, isopropylmyristate (oil), and Gelucire(r) 43/01 (lipid) adopting emulsion gelation technique. The beads were evaluated for their floating ability, DRT entrapment efficiency and in-vitro release. Gelucire(r) 43/01 /oil-based beads of the selected formula were coated using ethylcellulose and different plasticizers as polyethylene glycol 400 and triethyl citrate to retard the drug release. The coated beads were re-characterized. Finally, the best formulae were investigated for their in-vivo floating ability in dogs besides their delivery to the systemic circulation compared to drug powder in human volunteers. RESULTS: Incorporation of Gelucire(r) 43/01 to oil-based beads enhanced the in-vitro performance of the beads. Coated beads prepared using drug:sodium alginate ratio of 1:3 (w/w), 20% (w/v) isopropylmyristate, 20% (w/v) Gelucire(r) 43/01 showed promising in-vitro performance. The beads floated for 12 h in the dogs' stomach and produced three-fold increase of the total amount of DRT absorbed within 24 h compared to that of DRT powder. CONCLUSIONS: Gelucire(r) 43/01 /isopropylmyristate-based calcium alginate floating beads coated with ethylcellulose using either PEG 400 or TEC as plasticizers proved to be a successful dosage form in extending DRT release. PMID- 24236530 TI - Use of a modified transfixation pin cast for treatment of comminuted phalangeal fractures in horses. AB - OBJECTIVES: To (1) report a modified transfixation pin cast technique, using dorsal recumbency for fracture reduction, distal positioning of the pins in the epiphysis and distal metaphysis, and a hybrid cast, combining plaster of Paris (POP) and fiberglass casting, and (2) report outcome in 11 adult horses. STUDY DESIGN: Case series. ANIMALS: Adult horses (n = 11) with comminuted phalangeal fractures. METHODS: Horses were anesthetized and positioned in dorsal recumbency. The phalangeal fracture was reduced by limb traction using a cable attached to the hoof. Screw fixation in lag fashion of fracture fragments was performed when possible. Transfixation casting was performed using two 6.3 mm positive profile centrally threaded pins with the 1st pin placed in the epiphysis of the metacarpus/tarsus at the center of, or slightly proximal to, the condylar fossa and the 2nd one 3-4 cm proximal. A hybrid cast was applied. RESULTS: Forelimbs were involved in 9 horses and the hind limb in 2. Pins were maintained for a minimum of 6 weeks. No pin loosening was observed at the time of removal (6-8 weeks). A pony fractured the distal aspect of the metacarpus at the proximal pin. Nine horses survived (82%); none of the horses developed septic arthritis despite the distal location of the distal pin, close to the fetlock joint. CONCLUSION: This modified transfixation pin casting technique was associated with good pin longevity and could reduce the risk of secondary pin hole fractures and pin loosening. PMID- 24236531 TI - In vitro umbilical cord wrapping and torsion: possible cause of umbilical blood flow occlusion. AB - OBJECTIVE: Intrapartum fetal heart rate decelerations and bradycardia are often attributed to umbilical cord occlusion without knowing the anatomic basis of that occlusion. We hypothesized that umbilical cord twisting while looped around fetal parts could occlude blood flow. METHODS: Using an in vitro preparation, human umbilical cord veins were perfused at one end with water at approximately 40 cm H2O. The cords were looped around pipes that approximated the diameter of fetal body or limb parts, after which the perfused segment of cord was twisted until water flow stopped. The number of rotations needed to stop perfusion was recorded for each length of twisted cord (4, 6 and 8 cm) and for each pipe diameter. RESULTS: There were 21 completed studies. All cords demonstrated that a decreasing number of twists were needed to stop venous flow as the segment twisted became shorter (from 8 to 4 cm). For each segment length, the number of twists required to stop flow decreased as the pipe diameter narrowed. CONCLUSION: This model demonstrates that a wrapped umbilical cord, particularly with a short segment between the placental insertion and the fetal body part, may be predisposed to cord occlusion in response to fetal rotation. PMID- 24236532 TI - Acetylcholinesterase inhibition effects of marine fungi. AB - CONTEXT: To this day, there are no reports that marine compounds isolated from microorganisms of the Lianyungang area of China have been used for the treatment of Alzheimer's disease. OBJECTIVE: The present study was to isolate fungi from the sea sediment of the Lianyungang area and screen for acetylcholineseterase inhibition activities of ethyl acetate extracts. MATERIALS AND METHODS: Fungi were isolated from the sea sediment and fermented. After centrifugation, the supernate was extracted with ethyl acetate. The ethyl acetate extract was then fractionated into five fractions. Acetylcholinesterase inhibition activities of the ethyl acetate extracts and five sub-fractions were tested at a concentration of 500 MUg/mL with the Ellman's method. RESULTS: Forty-three marine fungi were isolated; 15 extracts inhibited acetylcholinestrease >50% and 3 extracts inhibited the acetylcholinesterase >80% at the concentration of 500 MUg/mL. The 3 extracts (L1705, S1101, SH0701) inhibited AChE dose-dependently with IC50 values of 11.3 +/- 1.2, 72.1 +/- 2.3, and 7.8 +/- 2.8 MUg/mL, respectively. After the extract of SH0701 was fractionated into five fractions, the ethyl acetate fraction possessed the highest acetylcholinesterase inhibitory activity with an inhibition rate of 71.55% at the concentration of 10 MUg/mL. The fungus SH0701 was identified as Aspergillus ochraceus SH0701 according to morphology and molecular identification. DISCUSSION AND CONCLUSION: The present results indicates that some ethyl acetate extracts of marine fungi isolated from Lianyungang area of China could inhibit AChE potently. Therefore, some novel AChE inhibitors might exist in those extracts. PMID- 24236534 TI - Multiregion shear thinning for subsequent static self-thickening in chitosan graft-polyacrylamide aqueous solution. AB - A special shear thinning phenomenon followed by static self-thickening in chitosan-graft-polyacrylamide (GPAM) aqueous solutions was investigated. This multiregion shear thinning can be defined as the first stage of the recently reported shear induced self-thickening (SIT) in our previous work. The three thinning regions (labeled as N1, N2, and N3) are considered very important, and they can reflex the complex variations of intermolecular interactions among and inside the aggregates in solution with increasing shear rate. To verify this multiregion shear thinning, a critical concentration of GPAM for this three region shear thinning was first investigated. Shear recovery tests with the maximal shear rates located in the N1-N3 were carried out to ascertain the crucial role of shear thinning in SIT. The mechanisms of these three shear thinning regions were proposed based on the dependence of shear rheological behavior on various conditions in each region, including GPAM concentration, grafting ratio, temperature, added hydrogen bonding breaker, and salt. The above results confirm that N1 is due to the breakage of the interactions among hydrogen bonding aggregates, while N2 and N3 are attributed to the progressive destruction of the aggregates. As the first stage of SIT, shear thinning can markedly break the original aggregate and expose additional hydrogen bonding stickers to reform more aggregates with bigger size, resulting in the final higher viscosity. PMID- 24236533 TI - Cross-coupling of remote meta-C-H bonds directed by a U-shaped template. AB - meta-C-H arylation and methylation of 3-phenylpropanoic acid and phenolic derivatives were developed using an easily removable nitrile template. The combination of a weakly coordinating U-shaped template and mono-protected amino acid ligand was crucial for the cross-coupling of C-H bonds with organoborons. PMID- 24236535 TI - Accurate quantitation of D+ fetomaternal hemorrhage by flow cytometry using a novel reagent to eliminate granulocytes from analysis. AB - BACKGROUND: Quantitation of fetomaternal hemorrhage (FMH) is performed to determine the dose of prophylactic anti-D (RhIG) required to prevent D immunization of D- women. Flow cytometry (FC) is the most accurate method. However, maternal white blood cells (WBCs) can give high background by binding anti-D nonspecifically, compromising accuracy. STUDY DESIGN AND METHODS: Maternal blood samples (69) were sent for FC quantitation of FMH after positive Kleihauer Betke test (KBT) analysis and RhIG administration. Reagents used were BRAD-3 fluorescein isothiocyanate (FITC; anti-D), AEVZ5.3-FITC (anti-varicella zoster [anti-VZ], negative control), anti-fetal hemoglobin (HbF)-FITC, blended two-color reagents, BRAD-3-FITC/anti-CD45-phycoerythrin (PE; anti-D/L), and BRAD-3 FITC/anti-CD66b-PE (anti-D/G). PE-positive WBCs were eliminated from analysis by gating. Full blood counts were performed on maternal samples and female donors. RESULTS: Elevated numbers of neutrophils were present in 80% of patients. Red blood cell (RBC) indices varied widely in maternal blood. D+ FMH values obtained with anti-D/L, anti-D/G, and anti-HbF-FITC were very similar (r = 0.99, p < 0.001). Correlation between KBT and anti-HbF-FITC FMH results was low (r = 0.716). Inaccurate FMH quantitation using the current method (anti-D minus anti VZ) occurred with 71% samples having less than 15 mL of D+ FMH (RBCs) and insufficient RhIG calculated for 9%. Using two-color reagents and anti-HbF-FITC, approximately 30% patients had elevated F cells, 26% had no fetal cells, 6% had D FMH, 26% had 4 to 15 mL of D+ FMH, and 12% patients had more than 15 mL of D+ FMH (RBCs) requiring more than 300 MUg of RhIG. CONCLUSION: Without accurate quantitation of D+ FMH by FC, some women would receive inappropriate or inadequate anti-D prophylaxis. The latter may be at risk of immunization leading to hemolytic disease of the newborn. PMID- 24236537 TI - Electromagnetic fields (UHF) increase voltage sensitivity of membrane ion channels; possible indication of cell phone effect on living cells. AB - The effects of ultra high frequency (UHF) nonionizing electromagnetic fields (EMF) on the channel activities of nanopore forming protein, OmpF porin, were investigated. The voltage clamp technique was used to study the single channel activity of the pore in an artificial bilayer in the presence and absence of the electromagnetic fields at 910 to 990 MHz in real time. Channel activity patterns were used to address the effect of EMF on the dynamic, arrangement and dielectric properties of water molecules, as well as on the hydration state and arrangements of side chains lining the channel barrel. Based on the varied voltage sensitivity of the channel at different temperatures in the presence and absence of EMF, the amount of energy transferred to nano-environments of accessible groups was estimated to address the possible thermal effects of EMF. Our results show that the effects of EMF on channel activities are frequency dependent, with a maximum effect at 930 MHz. The frequency of channel gating and the voltage sensitivity is increased when the channel is exposed to EMF, while its conductance remains unchanged at all frequencies applied. We have not identified any changes in the capacitance and permeability of membrane in the presence of EMF. The effect of the EMF irradiated by cell phones is measured by Specific Absorption Rate (SAR) in artificial model of human head, Phantom. Thus, current approach applied to biological molecules and electrolytes might be considered as complement to evaluate safety of irradiating sources on biological matter at molecular level. PMID- 24236539 TI - Day length dependent restructuring of the leaf transcriptome and metabolome in potato genotypes with contrasting tuberization phenotypes. AB - Recent advances have defined some of the components of photoperiodic signalling that lead to tuberization in potato including orthologues of FLOWERING LOCUS T (StSP6A) and CYCLING DOF FACTOR (StCDF1). The aim of the current study is to investigate the molecular basis of permissive tuber initiation under long days in Solanum tuberosum Neo-Tuberosum by comparative analysis with an obligate short day S. tuberosum ssp. Andigena accession. We show that the Neo-Tuberosum accession, but not the Andigena, contains alleles that encode StCDF1 proteins modified in the C-terminal region, likely to evade long day inhibition of StSP6A expression. We also identify an allele of StSP6A from the Neo-Tuberosum accession, absent in the Andigena, which is expressed under long days. Other leaf transcripts and metabolites that show different abundances in tuberizing and non tuberizing samples were identified adding detail to tuberization-associated processes. Overall, the data presented in this study highlight the subtle interplay between components of the clock-CONSTANS-StSP6A axis which collectively may interact to fine-tune the timing of tuberization. PMID- 24236540 TI - Average and local structural origins of the optical properties of the nitride phosphor La(3-x)Ce(x)Si6N11 (0 < x <= 3). AB - Structural intricacies of the orange-red nitride phosphor system La(3 x)Ce(x)Si6N11 (0 < x <= 3) have been elucidated using a combination of state-of the art tools, in order to understand the origins of the exceptional optical properties of this important solid-state lighting material. In addition, the optical properties of the end-member (x = 3) compound, Ce3Si6N11, are described for the first time. A combination of synchrotron powder X-ray diffraction and neutron scattering is employed to establish site preferences and the rigid nature of the structure, which is characterized by a high Debye temperature. The high Debye temperature is also corroborated from ab initio electronic structure calculations. Solid-state (29)Si nuclear magnetic resonance, including paramagnetic shifts of (29)Si spectra, are employed in conjunction with low temperature electron spin resonance studies to probes of the local environments of Ce ions. Detailed wavelength-, time-, and temperature-dependent luminescence properties of the solid solution are presented. Temperature-dependent quantum yield measurements demonstrate the remarkable thermal robustness of luminescence of La2.82Ce0.18Si6N11, which shows little sign of thermal quenching, even at temperatures as high as 500 K. This robustness is attributed to the highly rigid lattice. Luminescence decay measurements indicate very short decay times (close to 40 ns). The fast decay is suggested to prevent strong self-quenching of luminescence, allowing even the end-member compound Ce3Si6N11 to display bright luminescence. PMID- 24236538 TI - AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenstrom macroglobulinaemia. AB - Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti-tumour effects of a pan-BCL2 inhibitor, AT-101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenstrom macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT-101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase-dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT-101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA-treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT-101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy. PMID- 24236541 TI - Vitamin D deficiency is associated with mortality in patients with advanced liver cirrhosis. AB - BACKGROUND: Chronic liver disease is the fifth most common cause of mortality in Europe. Recently, vitamin D deficiency has been associated with an increased risk of mortality in the general population. As patients with advanced liver disease frequently exhibit vitamin D deficiency, we assessed for a possible association of vitamin D deficiency with survival in a cohort of patients with advanced liver disease. METHODS: Sixty-five patients with liver cirrhosis (median age, 58 years; range, 19-76 years; 66% male; Child-Pugh stage C, 46%) were included in our prospective single-centre survival study. Serum 25-hydroxyvitamin D concentrations were measured by chemiluminescence immunoassay. The optimal cut off was determined using receiver operating characteristic (ROC) and Kaplan-Meier analysis. Chi-square statistics and multivariate binary logistic regression analysis were also conducted. RESULTS: Median serum vitamin D levels were 8.2 ng/mL (range <4.0-95.8 ng/mL). Overall, 48% of patients (31/65) died during a 24 month follow-up period. ROC analysis determined a vitamin D level of 6.0 ng/mL as optimal cut-off for discriminating survivors from nonsurvivors. Kaplan-Meier analysis of survival confirmed low vitamin D levels as significant predictor of death (P = 0.012). Finally, multivariate analysis identified low vitamin D levels (OR = 6.3; 95% CI, 1.2-31.2; P = 0.012) and MELD scores (OR = 1.4; 95% CI, 1.2 1.7; P < 0.001) as independent predictors of survival. CONCLUSION: Low vitamin D levels are associated with increased mortality in patients with advanced liver disease. Thus, serum levels of vitamin D might represent a critical marker of survival in advanced liver cirrhosis. PMID- 24236542 TI - The viability of nitrone-alkene (3 + 2) cycloadditions in alkaloid biosynthesis. AB - Although evidence has mounted in recent years for the biosynthetic relevance of [4 + 2] cycloaddition reactions, other cycloadditions have received much less attention. Herein we used density functional theory (DFT) calculations to assess the viability of nitrone-alkene (3 + 2) cycloaddition reactions proposed to occur during the biosynthesis of several alkaloid natural products (flueggines and virosaines). The results of our calculations indicate that these reactions have low enough intrinsic barriers and diastereoselectivity that they can proceed without enzymatic intervention. PMID- 24236543 TI - Bladder cancer stem cells: biological and therapeutic perspectives. AB - Bladder cancer stem cell research is rapidly expanding based on the knowledge of cancer stem cells from various cancer types and normal stem cells as models. In various cancer types, cancer stem cells have been implicated in therapeutic resistance and relapse after initial therapy. Understanding how cancer stem cells differ from bulk cancer cells and how cancer stem cells contribute to relapse and resistance are essential to develop novel therapeutics to target cancer stem cells effectively. Here we review the latest information on bladder cancer stem cells, their biological characteristics, including their response to treatment, recurrence, immune context and technical problems encountered in bladder cancer stem cell research. PMID- 24236544 TI - Wetting states on circular micropillars with convex sidewalls after liquids contact groove base. AB - It is considered that the Cassie-Baxter wetting state should be transitioned to that of the Wenzel state if a water drop has contact with the base of a roughness groove. However, in recent tests on the leaf surfaces of three lotus varieties, we found that the transition did not occur. To explore the reason behind this, in this work we model the corresponding surface structures as circular micropillars with convex sidewalls, and derive an angle inequality for judging transition from Cassie-Baxter to Wenzel States. We also consider the transition on spherical microparticles, as well as that on circular micropillars with straight sidewalls. Finally, we validate the angle inequality through pressing tests on three lotus varieties and spherical microballs. PMID- 24236545 TI - Subclinical ketosis in dairy cows: prevalence and risk factors in grazing production system. AB - The purpose of this study was to estimate the prevalence of Subclinical ketosis (SCK) between 4 and 19 days in milk (DIM) in a grazing production system and investigate the importance of potential risk factors for SCK. This cross sectional study was conducted in dairy cows (n = 107), which had more of two parities. The concentration of beta-hydroxybutyric (BHB) in blood was quantified through a hand-held meter. Potential risk factors evaluated were calving interval (CI), milk yield in previous lactation, metritis, dystocia, calf sex (male), parity (<=3 vs. >=4) and pre-partum body condition score (BCS <= 3.5 vs. >=3.75). Prevalence of SCK was 10.3% (95% CI 4.7-15) between 4 and 19 DIM. Risk factors identified were the occurrence of both metritis and pre-partum BCS >= 3.75. Cows with metritis had 4.9 (95% CI 1.17-20.98) times more risk of developing SCK than cows without metritis. And the cows with pre-partum BCS >= 3.75 had 5.25 (95% CI 1.32-21.11) times more risk of developing SCK than cows with pre-partum BCS <= 3.5. Metritis could induce a lower feed intake and promote the development of SCK. High pre-partum BCS could induce a greater mobilization of body reserves altering liver function and aggravating post-partum NEB. The results are indicative of the expected prevalence of SCK in grazing production system. Factors associated could help to identify cattle at risk of SCK and improve the management of strategies to limit the effects. PMID- 24236547 TI - Antibacterial activity of gemini quaternary ammonium salts. AB - A series of gemini quaternary ammonium salts (chlorides and bromides), with various hydrocarbon chain and spacer lengths, were tested. These compounds exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria and were not mutagenic. The strongest antibacterial effect was observed for TMPG-10 Cl (against Pseudomonas aeruginosa ATCC 27853) and TMPG-12 Br (against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229 and clinical ESBL(+) isolate 434) surfactants. These compounds inhibited the adhesion of Staphylococcus epidermidis ATCC 35984 to a polystyrene surface and eradicated biofilm formed by P. aeruginosa PAO1. The activity of studied compounds was dependent on hydrocarbon chain length. PMID- 24236548 TI - Comparative effectiveness research and the regulation of drugs, biologics and devices. PMID- 24236546 TI - DNA recognition of 5-carboxylcytosine by a Zfp57 mutant at an atomic resolution of 0.97 A. AB - The Zfp57 gene encodes a KRAB (Kruppel-associated box) domain-containing C2H2 zinc finger transcription factor that is expressed in early development. Zfp57 protein recognizes methylated CpG dinucleotide within GCGGCA elements at multiple imprinting control regions. In the previously determined structure of the mouse Zfp57 DNA-binding domain in complex with DNA containing 5-methylcytosine (5mC), the side chains of Arg178 and Glu182 contact the methyl group via hydrophobic and van der Waals interactions. We examined the role of Glu182 in recognition of 5mC by mutagenesis. The majority of mutants examined lose selectivity of methylated (5mC) over unmodified (C) and oxidative derivatives, 5-hydroxymethylcytosine, 5 formylcytosine, and 5-carboxylcytosine (5caC), suggesting that the side chain of Glu182 (the size and the charge) is dispensable for methyl group recognition but negatively impacts the binding of unmodified cytosine as well as oxidized derivatives of 5mC to achieve 5mC selectivity. Substitution of Glu182 with its corresponding amide (E182Q) had no effect on methylated DNA binding but gained significant binding affinity for 5caC DNA, resulting in a binding affinity for 5caC DNA comparable to that of the wild-type protein for 5mC. We show structurally that the uncharged amide group of E182Q interacts favorably with the carboxylate group of 5caC. Furthermore, introducing a positively charged arginine at position 182 resulted in a mutant (E182R) having higher selectivity for the negatively charged 5caC. PMID- 24236549 TI - Are patient portals one key to unlocking the door for engaging patients in their healthcare? PMID- 24236551 TI - From methods to policy: Primum non nocere: reconciling patient-centered outcomes with evidence-based care. PMID- 24236552 TI - Interview: access to richer data promises to usher in a new era of insight into patient heterogeneity. PMID- 24236553 TI - The impact of mammography screening on breast cancer incidence. AB - Evaluation of: Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N. Engl. J. Med. 377, 1998-2005 (2012). Mammography screening must advance the time of diagnosis of breast cancer to be able to reduce the rate of death from breast cancer. This article examined the temporal effects of mammography on the stage-specific incidence of breast cancer in the USA from 1976 through to 2008. Despite substantial increases in the number of cases of early-stage breast cancer, only a marginal reduction was observed in the number of cases presenting with late-stage breast cancer. These results provide convincing evidence that mammography screening entails a substantial risk of detecting tumors that would not have become symptomatic during a woman's lifetime if no screening had taken place. To improve the effectiveness of screening mammography, more knowledge is needed on the natural history of breast cancer, especially the risk of progression from in situ to invasive breast cancer. PMID- 24236554 TI - Stakeholder engagement for comparative effectiveness research in cancer care: experience of the DEcIDE Cancer Consortium. AB - Stakeholder input is a critical component of comparative effectiveness research. To ensure that the research activities of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network, supported by the Agency for Healthcare Research and Quality, translate into the greatest impact for everyday practice and policy-making in cancer, we were tasked with soliciting stakeholder input regarding priority areas in cancer-related comparative effectiveness research for the DEcIDE Cancer Consortium. Given the increasing emphasis on stakeholder engagement in research, many investigators are facing a similar task, yet there is limited literature to guide such efforts, particularly in cancer care. To help fill this gap, we present our approach to operationalizing stakeholder engagement and discuss it in the context of other recent developments in the area. We describe challenges encountered in convening stakeholders from multiple vantage points to prioritize topics and strategies used to mitigate these barriers. We offer several recommendations regarding how to best solicit stakeholder input to inform comparative effectiveness research in cancer care. These recommendations can inform other initiatives currently facing the challenges of engaging stakeholders in priority setting for cancer. PMID- 24236555 TI - Unresolved tensions in consumer engagement in CER: a US research perspective. AB - Efforts to engage patients and consumers in comparative effectiveness research (CER) in the USA are still in the early stages, and the outcomes of these partnerships have yet to be fully understood or realized. Our work assisting federal agencies and national organizations who engage patients and consumers in CER reveal three unresolved tensions around the representation of the patient experience in the research process, the culture of research and capacity to partner with patients and consumers, and the conflict between the methodological approaches to CER and the outcomes of interest to patients and caregivers. Several approaches to address these tensions have emerged, yet resolving these tensions will require addressing many system-level challenges and building an evidence base for consumer engagement in CER. PMID- 24236556 TI - Comparing medical treatments for Crohn's disease. AB - The drugs available for inflammatory bowel disease are aminosalicylates, antibiotics, steroids, immunosuppressors and biologics. The effectiveness of these drugs has been evaluated in many randomized clinical trials, mainly versus placebo. Few studies have been conducted comparing the different drugs among themselves, owing to the methodological problems raised by comparative trials, such as sample size and blindness. This review focuses mainly on the randomized clinical trials that have compared different treatments. Of course comparisons are mainly between drugs used in a particular setting (mild, moderate and severe disease). However, on many occasions there is no homogeneity in these clinical settings, and therefore the results are difficult to interpret. PMID- 24236557 TI - Comparing radial and femoral access for coronary angiography and interventions. AB - Cardiac catheterization and coronary intervention via the radial approach is increasingly adopted as the preferred vascular access to avoid transfemoral vascular complications. Recent clinical trials have confirmed that radial access reduces vascular complications and local bleeding with similar procedural efficacy. Transradial access has inherent technical challenges, including smaller vessel size of the radial artery, arterial spasm and tortuosity involving the radial and subclavian arteries, which may undermine the procedural success of this approach. A number of strategies have been reported to minimize complications of radial access, including the use of hydrophilic introducer sheaths and smaller sheath sizes, administration of nitroglycerin and unfractionated heparin during the procedure, patent hemostasis of the radial artery and careful patient selection. Operators experienced in transradial percutaneous coronary intervention can achieve comparable clinical outcomes to the transfemoral approach and minimize vascular complications. Radial artery access is likely to become widely accepted as the preferred percutaneous coronary intervention approach. PMID- 24236558 TI - Study design elements for rigorous quasi-experimental comparative effectiveness research. AB - Quasi-experiments are likely to be the workhorse study design used to generate evidence about the comparative effectiveness of alternative treatments, because of their feasibility, timeliness, affordability and external validity compared with randomized trials. In this review, we outline potential sources of discordance in results between quasi-experiments and experiments, review study design choices that can improve the internal validity of quasi-experiments, and outline innovative data linkage strategies that may be particularly useful in quasi-experimental comparative effectiveness research. There is an urgent need to resolve the debate about the evidentiary value of quasi-experiments since equal consideration of rigorous quasi-experiments will broaden the base of evidence that can be brought to bear in clinical decision-making and governmental policy making. PMID- 24236559 TI - The value of linking hospital discharge and mortality data for comparative effectiveness research. AB - BACKGROUND: Linkage of US state hospital discharge records to state death certificate records offers the possibility of tracking long-term mortality outcomes across large, diverse patient populations, which may be useful for comparative effective analyses. AIM: To demonstrate the value of linking state community hospital discharge data to vital statistics death files for research by conducting a comparative effectiveness analysis. METHODS: Linked Patient Discharge Data and Vital Statistics Death Files from the California Office of Statewide Health Planning and Development were used to compare survival rates for patients with an elective repair for abdominal aortic aneurysm who received open aneurysm repair (OAR) versus endovascular aneurysm repair (EVAR). The sample consisted of 13,652 hospitalized patients who underwent an OAR or EVAR for abdominal aortic aneurysm between 1 July 2000 and 31 January 2006. Patients were matched using propensity scores (8966 patients in the matched sample). In hospital, 30-day, 1-year and 5-year mortality rates were compared between the OAR and EVAR populations, before and after propensity score matching. RESULTS: We found a few data anomalies (92 out of 13,652), primarily in patients' sex and date of death. The analysis revealed that in the matched cohort, in-hospital and 30-day postdischarge mortality rates were significantly lower following EVAR than OAR; however, consistent with previous clinical trials, differences in the 1- and 5-year rates were not statistically significant. CONCLUSION: The study demonstrates that linked US state discharge and mortality data can be a valuable resource for comparative effectiveness analyses. In particular, this approach may be useful when generally available data sets such as Medicare claims data limit the generalizability of findings. Policy-makers and others should consider greater investments in these data. PMID- 24236560 TI - Dissemination and implementation of comparative effectiveness evidence: key informant interviews with Clinical and Translational Science Award institutions. AB - AIM: To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. MATERIALS & METHODS: Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. RESULTS & CONCLUSIONS: The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems. PMID- 24236561 TI - Patterns of treatment, healthcare utilization and costs by lines of therapy in metastatic breast cancer in a large insured US population. AB - AIM: Metastatic breast cancer guidelines contain multiple lines of treatment and regimens; however, little data on therapeutic patterns and costs is available from real-world clinical practice. This descriptive study reports chemotherapy and biologic use, healthcare utilization and costs by line of therapy in a large insured US population. MATERIALS & METHODS: Adult women with newly diagnosed metastatic breast cancer (between 2005 and 2009) were identified from MarketScan(r) databases containing medical and pharmacy claims of >40 million enrollees insured with >100 US health plans. Descriptive statistics were reported for use, duration and mean per patient per month costs across four lines of therapy. RESULTS: Out of 7767 patients identified (mean [standard deviation] age = 58.2 [12] years), >=50% received a subsequent line of therapy across the four lines (line 2: n = 4077; line 3: n = 2033; line four: n = 1059). The top two chemotherapies were paclitaxel and capecitabine in lines one and two, and paclitaxel and gemcitabine in lines three and four. The top two biologics were trastuzumab and bevacizumab across the multiple lines of treatments. Duration (mean, standard deviation and median days) varied across multiple lines of treatments: 162.7, 176.9 and 108.0 in line one; 147.5, 146.7 and 99.0 in line two; 139.9, 131.1 and 99.0 in line three; and 130.9, 123.4 and 94.0 in line four, respectively. Mean per patient per month costs decreased with increasing follow up from US$13,147 (<6 months) to US$11,610 (7-12 months) to US$10,219 (12-24 months) to US$9,192 (24-36 months) to US$7,384 (>36 months). Cumulative costs increased with follow-up, from US$78,882 (<6 months) to US$443,062 (>36 months). CONCLUSION: Longer follow-up, regardless of number of lines of therapy, was associated with higher cumulative, but lower monthly, costs. Delaying progression and improving survival with more individualized treatment regimens may help slow the rate of increasing long-term costs of metastatic breast cancer treatment and care. PMID- 24236563 TI - Transition to dialysis: controversies in its timing and modality [corrected]. PMID- 24236566 TI - Antimicrobial metabolites from a novel halophilic actinomycete Nocardiopsis terrae YIM 90022. AB - A quinoline alkaloid 1 and five known compounds (2-6) were isolated from a novel halophilic actinomycete Nocardiopsis terrae YIM 90022, and their structures were determined by spectroscopic studies as 4-oxo-1,4-dihydroquinoline-3-carboxamide (1), p-hydroxybenzoic acid (2), N-acetyl-anthranilic acid (3), indoly-3 carboxylic acid (4), cyclo(Trp-Gly) (5) and cyclo(Leu-Ala) (6). Compound 1 was isolated from natural resources for the first time. Compounds 1 and 3 showed antimicrobial activities against some plant pathogens. PMID- 24236567 TI - Signalling pathways in succinate dehydrogenase B-associated renal carcinoma. AB - AIMS: Renal tumours have recently been described in association with mutations in the gene encoding the B subunit of succinate dehydrogenase, a mitochondrial Krebs cycle and electron transport chain enzyme (SDHB-associated renal cell carcinomas). The aim of this study was to investigate the roles of different signalling pathways in the pathogenesis of these tumours. METHODS AND RESULTS: We used immunohistochemistry and antibodies against phospho-specific epitopes to examine the activity of three potential signalling pathways in tumour cells of three genetically confirmed cases of SDHB-associated renal cell carcinomas. We found no evidence supporting a role for either the mTOR [p-mTOR (Ser2448), p-S6 riboprotein (Ser235/236)] or hypoxia-inducible (carbonic anhydrase 9 and EGFR) pathways. However, there was immunohistochemical reactivity for phosphorylated AMP-dependent kinase (p-AMPK Thr172) and glycogen synthase kinase 3 (GSK3) phosphorylation (p-GSK3 Ser12), and nuclear expression of cyclin D1. CONCLUSIONS: We suggest that these tumours may arise through a mechanism involving ATP depletion, activation of AMPK, and induction of cyclin D1, and that this may be a unique pathway of tumour development that has the potential for therapeutic intervention in these rare tumours. PMID- 24236568 TI - Osthole induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. AB - CONTEXT: Osthole [7-methoxy-8-(3-methyl-2-butenyl) coumarin] isolated from the fruit of Cnidium monnieri (L.) Cuss, one of the commonly used Chinese medicines listed in the Shennong's Classic of Materia Medica in the Han Dynasty, had remarkable antiproliferative activity against human hepatocellular carcinoma HepG2 cells in culture. OBJECTIVES: This study evaluated the effects of osthole on cell growth, nuclear morphology, cell cycle distribution, and expression of apoptosis-related proteins in HepG2 cells. MATERIALS AND METHODS: Cytotoxic activity of osthole was determined by the MTT assay at various concentrations ranging from 0.004 to 1.0 umol/ml in HepG2 cells. Cell morphology was assessed by Hoechst staining and fluorescence microscopy. Apoptosis and cell-cycle distribution was determined by annexin V staining and flow cytometry. Apoptotic protein levels were assessed by Western blot. RESULTS: Osthole exhibited significant inhibition of the survival of HepG2 cells and the half inhibitory concentration (IC50) values were 0.186, 0.158 and 0.123 umol/ml at 24, 48 and 72 h, respectively. Cells treated with osthole at concentrations of 0, 0.004, 0.02, 0.1 and 0.5 MUmol/ml showed a statistically significant increase in the G2/M fraction accompanied by a decrease in the G0/G1 fraction. The increase of apoptosis induced by osthole was correlated with down-regulation expression of anti-apoptotic Bcl-2 protein and up-regulation expression of pro-apoptotic Bax and p53 proteins. CONCLUSION: Osthole had significant growth inhibitory activity and the pro-apoptotic effect of osthole is mediated through the activation of caspases and mitochondria in HepG2 cells. Results suggest that osthole has promising therapeutic potential against hepatocellular carcinoma. PMID- 24236569 TI - The effect of planned baby care education given to primiparous mothers on maternal attachment and self-confidence levels. AB - This study was conducted to examine the effect of planned baby care education on maternal attachment and self-confidence levels in primiparous mothers. The research was carried out using a pre-test, post-test, quasi-experimental design with a control group. In the intervention group, mothers were given planned baby care education and an education booklet. Both the median maternal attachment score and the mean self-confidence score increased by statistically significant levels in the intervention group, whereas there were no significant differences in the control group. It is recommended that primiparous mothers in particular should receive education regarding baby care. PMID- 24236570 TI - Clinical predictors of postoperative hemoglobin drift. AB - BACKGROUND: The decision to transfuse red blood cells in surgical patients should be based on multiple clinical variables, rather than on isolated hemoglobin (Hb) measurements alone. An important but often unrecognized clinical variable is the postoperative downward drift in Hb concentration (Hb drift), but the etiology, predictors, and time course of Hb drift are not well understood. STUDY DESIGN AND METHODS: Data were retrospectively collected for patients who did not receive postoperative transfusion. Initially, 11 common surgical procedures from one institution (n=3179) were compared to assess clinical predictors of Hb drift. Data were analyzed in detail for two procedures associated with a large Hb drift (Whipple [n=82] and lumbar spinal fusion [n=74]), to determine the clinical predictors and temporal pattern of postoperative Hb drift. RESULTS: Surgical procedures with greater intraoperative intravenous (IV) fluid and blood requirements had greater postoperative Hb drift. The maximum Hb drifts after the Whipple and spinal fusion procedures were -2.5 +/- 1.1 g/dL (occurring on Day 4, p<0.0001) and -1.8 +/- 2 g/dL (on Day 3, p<0.0001), respectively. After the nadir, a 0.6 g/dL upward Hb drift (p<0.0001) occurred after both procedures, resulting in a total drift after Whipple and spinal fusion of -1.9 +/- 1.2 g/dL (p<0.0001) and -1.3 +/- 1.2 g/dL (p<0.0001), respectively. Type of surgery (p=0.03), intraoperative blood loss (p=0.003), and a positive perioperative fluid balance (p=0.0008) were independent predictors of Hb drift. CONCLUSIONS: Postoperative Hb drift was greater after surgical procedures with greater intraoperative IV fluid and blood requirements. Recognition of Hb drift may be an important facet of perioperative patient blood management. PMID- 24236571 TI - Transition structures of the ene reactions of cyclopropene. AB - The transition structures for the ene reactions of cyclopropene with ethylene, propene, and cyclopropene have been located with ab initio molecular orbital calculations and the 6-31G* basis set and by DFT calculations with the Becke3LYP functional and the 6-31G* basis set. Several of the transition structures have also been located with CASSCF calculations. Energies of all stationary points were also evaluated with second-order Moller-Plesset theory using the RHF/6-31G* optimized geometry. The geometries of each transition structure and the energetics of each reaction are discussed and compared to the ene reaction of propene with ethylene. Calculations show that the cyclopropene ene reactions have much lower activation barriers than the propene-ethylene ene reaction, in agreement with experimental results. The transition structures have varying degrees of asynchronicity. The stabilities of the possible radical intermediates for each reaction are reflected in the geometries of the transition structures. The relief of strain in a cyclopropene, when acting as the enophile, accounts for the energetic differences in these reactions. The endo transition structure for the dimerization is lower in energy than the exo transition structure by 2.7 kcal/mol at the Becke3LYP/6-31G* + ZPE level of theory. Secondary orbital overlap of a CH bond of the enophile with the pi-system at the central carbon of the ene is proposed to account for the preference for the endo transition structure. Barely stable diradical intermediates have been found for both endo and exo cyclopropene dimerization reactions, but it is likely that they are artifacts of the current level of theory. PMID- 24236572 TI - Lipid membrane association of myelin proteins and peptide segments studied by oriented and synchrotron radiation circular dichroism spectroscopy. AB - Myelin-specific proteins are either integral or peripheral membrane proteins that, in complex with lipids, constitute a multilayered proteolipid membrane system, the myelin sheath. The myelin sheath surrounds the axons of nerves and enables rapid conduction of axonal impulses. Myelin proteins interact intimately with the lipid bilayer and play crucial roles in the assembly, function, and stability of the myelin sheath. Although myelin proteins have been investigated for decades, their structural properties upon membrane surface binding are still largely unknown. In this study, we have used simplified model systems consisting of synthetic peptides and membrane mimics, such as detergent micelles and/or lipid vesicles, to probe the conformation of peptides using synchrotron radiation circular dichroism spectroscopy (SRCD). Additionally, oriented circular dichroism spectroscopy (OCD) was employed to examine the orientation of myelin peptides in macroscopically aligned lipid bilayers. Various representative peptides from the myelin basic protein (MBP), P0, myelin/oligodencrocyte glycoprotein, and connexin32 (cx32) were studied. A helical peptide from the central immunodominant epitope of MBP showed a highly tilted orientation with respect to the membrane surface, whereas the N-terminal cytoplasmic segment of cx32 folded into a helical structure that was only slightly tilted. The folding of full-length myelin basic protein was, furthermore, studied in a bicelle environment. Our results provide information on the conformation and membrane alignment of important membrane binding peptides in a membrane-mimicking environment, giving novel insights into the mechanisms of membrane binding and stacking by myelin proteins. PMID- 24236573 TI - Weight maintenance over 12 months after weight loss resulting from participation in a 12-week randomised controlled trial comparing all meal provision to self directed diet in overweight adults. AB - BACKGROUND: The results of weight maintenance after initial weight loss are reported infrequently, although, when they have been reported, the outcomes are generally poor and weight regain is common. METHODS: After an initial 12-week randomised intervention comparing all meal provision against a self-directed energy restriction, participants re-consented to participate in a follow-on study. Participants were given the option to choose to continue with the same dietary intervention (either all meal provision (provided free of charge) or self directed diet) or change to the other diet for a further 12 weeks. Participants were followed up at 4-weekly intervals during both intervention periods (a total of 24 weeks), with a final follow up at 12 months. RESULTS: Eighty-five out of 86 individuals who completed the original 12-week randomised phase chose to continue on to the follow-up study. No significant differences in further weight loss between groups (P = 0.138) [mean (SEM): -3.4% (1.1%) for all meal provision only; -3.4% (0.6%) self-directed then all meal provision; -1.1% (1.2%) all meal provision then self-directed] were seen after a further 12 weeks. Meal provision for a total of 24 weeks resulted in 67% of individuals losing at least 10% body weight. The groups switching from self-directed dieting to meal provision (or vice versa) were the only groups to have a lower mean weight at 12 months than at the start of the follow-on study. CONCLUSIONS: Structured support for 24 weeks followed by 28 weeks of self-care can result in weight maintenance, with initial weight loss maintained at 12 months from enrolling on a 12-week weight loss intervention, with a 12-week follow-on period. PMID- 24236574 TI - Medium-chain sugar amphiphiles: a new family of healthy vegetable oil structuring agents. AB - Vegetable oils are frequently structured to enhance their organoleptic and mechanical properties. This is usually achieved by increasing the net amount of saturated and/or trans fatty acids in the oil. With the risk of coronary heart diseases associated with these fatty acids, the food industry is looking for better alternatives. In this context, the medium-chain dialkanoates of low calorie sugars (sugar alcohol dioctanoates) are investigated as a healthy alternative structuring agent. Precursors of sugar amphiphiles, being FDA approved GRAS materials, exhibited high cell viability at a concentration ~50 MUg/mL. They readily formed nanoscale multilayered structures in an oil matrix to form a coherent network at low concentrations (1-3 wt %/v), which immobilized a wide range of oils (canola, soybean, and grapeseed oils). The structuring efficiency of sugar amphiphiles was computed in terms of mechanical, thermal, and structural properties and found to be a function of its type and concentration. PMID- 24236575 TI - The in vitro genotoxic effect of Tucuma (Astrocaryum aculeatum), an Amazonian fruit rich in carotenoids. AB - Tucuma (Astrocaryum aculeatum) is an Amazonian fruit that presents high levels of carotenoids and other bioactive compounds such as quercetin. The extracts of tucuma peel and pulp present strong antioxidant activity which illustrate an elevated concentration that causes cytotoxic effects in human peripheral blood mononuclear cells (PBMCs). This study performed additional investigations to analyze the potential genotoxic effects of the tucuma extracts on PBMCs. The genotoxicity was evaluated by DNA fragmentation, Comet assay, and chromosomal instability G-band assays. The acute tucuma extract treatment showed genoprotective effects against DNA denaturation when compared with untreated PBMC cells. However, in the experiments with 24 and 72 h treatments to tucuma treatments, we observed low genotoxicity through a concentration of 100 MUg/mL, some genotoxic effects related to intermediary concentrations (100-500 MUg/mL), and more pronounced genotoxic effects on higher tucuma extract concentrations. After 24 h of treatment, the reactive oxygen species were similar among treatments and PBMC control groups. However, the caspase-1 activity related to the apoptosis and pyroptosis process increased significantly in higher tucuma concentrations. In summary, tucuma extracts, despite their higher antioxidant content and antioxidant activity, would present PBMCs genotoxic effects that are dependent on concentration and time exposition. These results need to be considered in future in vitro and in vivo studies of tucuma effects. PMID- 24236577 TI - Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. AB - A systematic review and meta-analysis were performed to investigate the quantity and quality of the current evidence regarding the effect of different probiotic strains in the treatment of functional gastrointestinal disorders (FGID) in children and adolescents. CONCLUSION: Probiotics are more effective than placebo in the treatment of patients with abdominal pain-related FGID, especially with respect to patients with irritable bowel syndrome. To date, however, probiotics have not proved effective for children with functional constipation. PMID- 24236576 TI - NMDA receptors and the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway are implicated in the antidepressant-like action of the ethanolic extract from Tabebuia avellanedae in mice. AB - Bark infusion of Tabebuia avellanedae Lorentz ex Griseb is consumed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. It was recently demonstrated that the extract from this plant has antidepressant properties. The present study was aimed at investigating the contribution of N-methyl-D-aspartate (NMDA) receptors and the L-arginine-nitric oxide (NO)-cyclic guanosine 3'5'-monophosphate (cGMP) pathway to the antidepressant-like action of the ethanolic extract from T. avellanedae (EET) in the tail suspension test (TST). The anti-immobility effect of the extract (30 mg/kg, orally [p.o.]) was prevented by pretreatment of mice with NMDA (0.1 pmol/site, intracerebroventicular [i.c.v.]), L-arginine (750 mg/kg, intraperitoneally [i.p.]), and sildenafil (5 mg/kg, i.p.). Additionally, the combination of MK-801 (0.01 mg/kg, p.o.), 7-nitroindazole (25 mg/kg, i.p.), and 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30 pmol/site, i.c.v.) with a subeffective dose of EET (1 mg/kg, p.o.) produced a synergistic antidepressant like effect in the TST, without causing significant alterations in the locomotor activity. Moreover, the administration of an effective dose of EET (30 mg/kg, p.o.) produced a reduction in NOx levels in the cerebral cortex. Conversely, a subeffective dose of EET (1 mg/kg, p.o.) caused no changes in the cortical NOx levels. Results suggest that the antidepressant-like effect of EET in the TST is dependent on a blockade of NMDA receptor activation and inhibition of NO-cGMP synthesis, significantly extending literature data about the antidepressant-like action of this plant and reinforcing the notion that this plant may be useful in the management of depressive disorders. PMID- 24236578 TI - One-pot synthesis of 7,9-dialkylpurin-8-one analogues: broad substrate scope. AB - The one-pot and direct synthesis of 7,9-dialkylpurin-8-one analogues with broad substrate scope has been developed. This copper-catalyzed C-H oxidation reaction could avoid multistep synthesis of quaternary ammonium salts and expand the scope of halogenated alkanes. Moreover, benzimidazole derivatives are also applicable in the catalytic system. PMID- 24236579 TI - Let us not be unfair to asexuals: their ephemerality may be explained by neutral models without invoking any evolutionary constraints of asexuality. AB - Phylogenetic studies typically demonstrate lower evolutionary ages of clones, relative to their sexual ancestors. This has often been attributed to heightened extinction risk of asexual organisms. We previously criticized such interpretations and demonstrated that the life span of clones is ultimately limited by neutral drift depending on the rate at which new clones are spawned into an asexual community of a finite size. Therefore, it is important to investigate whether the natural rates of such influxes are sufficiently high to account for the relative ephemerality of clones without assuming their increased extinction rate. I applied the neutral clonal turnover model to phylogenies of polyploid asexual ferns and simulated the coalescent trees over a wide range of demographic structures and sampling schemes. On parameterizing the model with biologically relevant estimates of population sizes and plant polyploidization rates, simulated clonal assemblages appeared younger than their sexual counterparts even in the absence of selection against clones. Therefore, differences observed between the ages of sexual and clonal lineages may be explained by the neutral clonal turnover. Researchers should consider the possibility that natural clones may get lost by neutral drift before their fate could eventually be affected by any long-term constraints of asexuality. PMID- 24236580 TI - Should all patients with asthma receive statins? PMID- 24236581 TI - The bronchial microbiome and asthma phenotypes. PMID- 24236582 TI - Socioeconomic status, race/ethnicity, and asthma in youth. PMID- 24236583 TI - The yin and yang of indoor airborne exposures to endotoxin. PMID- 24236584 TI - Endobronchial ultrasound-guided transbronchial needle aspiration for lymphoma: the final frontier. PMID- 24236585 TI - The lung microbiome and viral-induced exacerbations of chronic obstructive pulmonary disease: new observations, novel approaches. PMID- 24236586 TI - Carbon monoxide in small doses--a good thing? PMID- 24236587 TI - Microbial airway colonization: a cause of asthma and pneumonia? PMID- 24236588 TI - Various approaches to clinically related research can yield helpful insight. A personal perspective. AB - Attending two recent meetings (the joint American Physician Scientists Association, American Society of Clinical Investigation, and Association of American Physicians meeting and the American Thoracic Society meeting) and listening to state of the art presentations, viewing research posters, and interacting with young scientists about so much new and exciting human research rekindled my thoughts about how one could now begin research. For me this occurred, with excellent mentoring and supervision, as first a descriptive "looking" approach to identify host immunity components in a variety of animal models and then manipulating these models to mimic disease processes, focusing on the respiratory tract and innate immunity. Next, we moved to characterize these host immunity components in normal humans, before applying these to in vitro and clinical illness situations for patients. The intent of this research sequence was to better describe and manipulate immunopathology relevant to disease. A bench-to-patient approach, mostly descriptive and "looking," was the path. I have illustrated these steps with applicable references. Now seems such a crucial time to further scientific knowledge and to foster personalized medicine, despite a period of financial restraint. We need discussion of ways to best approach "looking" for still unknown basic information about the human respiratory system. Two special examples are identifying the still unknown cells in human lung tissue and their functions and manipulating the extensive respiratory microbiome. PMID- 24236589 TI - An unusual retrocardiac density. PMID- 24236590 TI - Assessing adherence to inhaled medication in difficult-to-treat asthma. PMID- 24236591 TI - Reply: Assessing adherence to inhaled medication in difficult-to-treat asthma. PMID- 24236593 TI - Reply: Moving forward in sepsis research. PMID- 24236592 TI - Moving forward in sepsis research. PMID- 24236594 TI - The dynamics of polymicrobial biofilms. PMID- 24236595 TI - Obesity paradox? PMID- 24236596 TI - Pulmonary metastasis from urothelial carcinoma showing progressive multiple cystic lesions. PMID- 24236597 TI - Fat in fibrosis. PMID- 24236598 TI - Temporal trends in use of sildenafil among pediatric patients. PMID- 24236601 TI - Interbronchial fistula by endobronchial tuberculosis. PMID- 24236602 TI - Effect of Er:YAG laser irradiation on bonding property of zirconia ceramics to resin cement. AB - OBJECTIVE: This study aimed to investigate whether or not an erbium: yttrium aluminum-garnet (Er:YAG) laser could improve the bonding property of zirconia ceramics to resin cement. BACKGROUND DATA: Surface treatments can improve the bonding properties of dental ceramics. However, little is known about the effect of Er:YAG laser irradiated on zirconia ceramics. MATERIALS AND METHODS: Specimens of zirconia ceramic pieces were made, and randomly divided into 11 groups according to surface treatments, including one control group (no treatment), one air abrasion group, and nine Er:YAG laser groups. The laser groups were subdivided by applying different energy intensities (100, 200, or 300 mJ) and irradiation times (5, 10, or 15 sec). After surface treatments, ceramic pieces had their surface morphology observed, and their surface roughness was measured. All specimens were bonded to resin cement. Shear bond strength was measured after the bonded specimens were stored in water for 24 h, and additionally aged by thermocycling. Statistical analyses were performed using one way analysis of variance (ANOVA) and Tukey's test for shear bond strength, and Dunnett's t test for surface roughness, with alpha=0.05. RESULTS: Er:YAG laser irradiation changed the morphological characteristics of zirconia ceramics. Higher energy intensities (200, 300 mJ) could roughen the ceramics, but also caused surface cracks. There were no significant differences in the bond strength between the control group and the laser groups treated with different energy intensities or irradiation times. Air abrasion with alumina particles induced highest surface roughness and shear bond strength. CONCLUSIONS: Er:YAG laser irradiation cannot improve the bonding property of zirconia ceramics to resin cement. Enhancing irradiation intensities and extending irradiation time have no benefit on the bond of the ceramics, and might cause material defect. PMID- 24236603 TI - Exploring the potential of hierarchical generalized linear models in animal breeding and genetics. PMID- 24236604 TI - Linear and Poisson models for genetic evaluation of tick resistance in cross-bred Hereford x Nellore cattle. AB - Cattle resistance to ticks is measured by the number of ticks infesting the animal. The model used for the genetic analysis of cattle resistance to ticks frequently requires logarithmic transformation of the observations. The objective of this study was to evaluate the predictive ability and goodness of fit of different models for the analysis of this trait in cross-bred Hereford x Nellore cattle. Three models were tested: a linear model using logarithmic transformation of the observations (MLOG); a linear model without transformation of the observations (MLIN); and a generalized linear Poisson model with residual term (MPOI). All models included the classificatory effects of contemporary group and genetic group and the covariates age of animal at the time of recording and individual heterozygosis, as well as additive genetic effects as random effects. Heritability estimates were 0.08 +/- 0.02, 0.10 +/- 0.02 and 0.14 +/- 0.04 for MLIN, MLOG and MPOI models, respectively. The model fit quality, verified by deviance information criterion (DIC) and residual mean square, indicated fit superiority of MPOI model. The predictive ability of the models was compared by validation test in independent sample. The MPOI model was slightly superior in terms of goodness of fit and predictive ability, whereas the correlations between observed and predicted tick counts were practically the same for all models. A higher rank correlation between breeding values was observed between models MLOG and MPOI. Poisson model can be used for the selection of tick-resistant animals. PMID- 24236605 TI - Direct and maternal genetic effects for preweaning growth in Retinta cattle estimated by a longitudinal approach throughout the calving trajectory of the cow. AB - The direct and maternal genetic effects were estimated for the preweaning growth of Retinta calves with a multitrait model across parities, using a longitudinal approach with random regression models (RRM). The 120 (P120) and 180 days (P180) weights (5972 calves) were considered as different traits in each calving. The heritability of direct effect across parities was on average 0.37 for P120 and 0.58 for P180, slightly higher than the estimates by univariate (0.30 and 0.56) and bivariate models (0.30 and 0.51, respectively). The heritability for maternal effects was 0.16 for P120 and 0.26 for P180 and very similar by uni- (0.16 and 0.23) and multivariate model (0.16 and 0.22, respectively). The correlation between direct and maternal effects by RRM showed a pronounced antagonism -0.64 for P120 and -0.78 for P180), likewise uni- (-0.62 and -0.72) and multivariate case (-0.64 and -0.74, respectively). The preweaning weights should be considered as different traits across parities, because the genetic correlations were different from unity. The RRM also allowed us to estimate all the parameters throughout the calving trajectory of the cow. The use of multiple traits RRM across parities can provide very useful information for the breeding programmes. PMID- 24236606 TI - Genetic background of claw disorders in the course of lactation and their relationships with type traits. AB - Random regression threshold animal models were applied to binary longitudinal claw disorder data for studying genetic parameters of all claw disorders (ACD), as well as to claw disorders divided into different categories: non-purulent claw disorders (NPCD), purulent claw disorders (PCD), dermatitis digitalis (DD), sole ulcer (SU), phlegmona (PH), laminitis (LAM) and interdigital hyperplasia (IH) in the course of lactation. Claw disorder data were obtained from 26,651 Holstein cows kept in 15 large-scale contract herds in the region of Thuringia over a period of 5 years from 2007 to 2012. If a cow had one or more entries of the same disorder, for example, sole ulcer, within an interval of 30 days, she was scored with a '1', and otherwise, she received a score of '0' for healthy. Heritabilities for the same disorder were relatively stable between DIM 50 and DIM 300, but they tended to increase in early and late lactation. Highest heritabilities in the range from 0.20 to 0.34 were estimated for IH, and lowest heritabilities were realized for LAM (~ 0.05). Genetic correlations for same traits between different DIMs were high for adjacent test days, but close to zero for distant test days. The relationship between the sire EBVs for claw disorders and official sire EBVs for the type traits 'foot angle' was slightly antagonistic with correlation coefficients in the range from 0.05 (DD) to 0.33 (PH). Correlations between lactation EBVs for hock quality, rear leg rear view and the feet and leg index with EBVs for claw disorders were slightly favourable and ranged between -0.01 (rear leg rear view correlated with SU) and -0.43 (hock quality correlated with PH). Regarding daily EBVs for claw disorders, the strongest correlation coefficient was of value -0.46 (LAM early in lactation correlated with the feet and leg index). Genetic parameters from the random regression model were verified by applying a single-trait repeatability model. Correlation coefficients between lactation EBVs from the random regression model and lactation EBVs from the repeatability model for the same claw disorder were close to 1. Correlations were lower between EBVs from single test days and lactation EBVs from the repeatability models, with a minimal value of 0.58 for PCD measured at day 20. PMID- 24236607 TI - Genetic parameters of pelt character, feed efficiency and size traits in Finnish blue fox (Vulpes lagopus). AB - Pelt character traits (size, quality, colour clarity, darkness) are important economic traits in blue fox breeding. Better feed efficiency (FE) is another economically important and new breeding goal for fur animals. The purpose of this study was to determine the correlations between pelt character traits, FE and size traits and to estimate genetic parameters for pelt character traits. Pelt size (pSIcm ) had a high positive genetic correlation with animal grading size (gSI), final body weight (BWFin), body length and daily gain (DG), and a moderate correlation with body condition score (BCS). Animal body length and BCS (describing fatness) were considered as genetically different traits. Genetic correlations between pelt quality and size traits were estimated without precision and did not differ from zero, but colour clarity (pCL) had a low antagonistic genetic correlation with FE. Pelt size and DG had a favourable genetic correlation with FE but a fairly high unfavourable genetic correlation with dry matter feed intake. The current emphasis on selection for larger animal and pelt size improves FE indirectly, but selection for larger pelt size favours fast-growing and fat individuals and simultaneously increases feed intake. The detected genetic connections between FE, size, feed intake and pCL should be taken into account in the Finnish blue fox breeding programme. PMID- 24236608 TI - Interplay between heritability, genetic correlation and economic weighting in a selection index with and without genomic information. AB - The availability of genomic information demands proper evaluation on how the kind (phenotypic versus genomic) and the amount of information influences the interplay of heritability (h(2)), genetic correlation (r(GiGj)) and economic weighting of traits with regard to the standard deviation of the index (sigmaI). As sigmaI is directly proportional to response to selection, it was the chosen parameter for comparing the indices. Three selection indices incorporating conventional and genomic information for a two trait (i and j) breeding goal were compared. Information sources were chosen corresponding to pig breeding applications. Index I incorporating an own performance in trait j served as reference scenario. In index II, additional information in both traits was contributed by a varying number of full-sibs (2, 7, 50). In index III, the conventional own performance in trait j was combined with genomic information for both traits. The number of animals in the reference population (NP = 1000, 5000, 10,000) and thus the accuracy of GBVs were varied. With more information included in the index, sigmaI became more independent of r(GiGj), h(j)(2) and relative economic weighting. This applied for index II (more full-sibs) and for index III (more accurate GBVs). Standard deviations of index II with seven full-sibs and index III with NP = 1000 were similar when both traits had the same heritability. If the heritability of trait j was reduced (h(j)(2) = 0.1), sigmaI of index III with NP = 1000 was clearly higher than for index II with seven full-sibs. When enhancing the relative economic weight of trait j, the decrease in sigmaI of the conventional full-sib index was much stronger than for index III. Our results imply that NP = 1000 can be considered a minimum size for a reference population in pig breeding. These conclusions also hold for comparing the accuracies of the indices. PMID- 24236609 TI - Genomewide association for a dominant pigmentation gene in sheep. AB - Most published genomewide association studies (GWAS) in sheep have investigated recessively inherited monogenic traits. The objective here was to assess the feasibility of performing GWAS for a dominant trait for which the genetic basis was already known. A total of 42 Manchega and Rasa Aragonesa sheep that segregate solid black or white coat pigmentation were genotyped using the SNP50 BeadChip. Previous analysis in Manchegas demonstrated a complete association between the pigmentation trait and alleles of the MC1R gene, setting an a priori expectation for GWAS. Multiple methods were used to identify and quantify the strength of population substructure between black and white animals, before allelic association testing was performed for 49,034 SNPs. Following correction for substructure, GWAS identified the most strongly associated SNP (s26449) was also the closest to the MC1R gene. The finding was strongly supported by the permutation tree-based random forest (RF) analysis. Importantly, GWAS identified unlinked SNP with only slightly lower p-values than for s26449. Random forest analysis indicated these were false positives, suggesting interpretation based on both approaches was beneficial. The results indicate that a combined analytical approach can be successful in studies where a modest number of animals are available and substantial population stratification exists. PMID- 24236610 TI - On the origin of the Slovenian Cika cattle. AB - In 2002, it was discovered that several Cika cattle in the mountain areas of Slovenia had escaped the official policy of cross-breeding. Here, we report a genetic characterization to assess their status as autochthonous breed. We compared genotypes for 14 microsatellite markers in 150 Cika cattle individuals with data from 16 Central European cattle breeds. We show that Cika cattle are genetically as diverse as other Eastern Alpine breeds, are more diverse than Austrian Simmental but less than the Balkan Busha cattle. STRUCTURE analysis showed Pinzgauer admixture in several individuals but also indicated a unique genetic identity for Cika. This analysis also allowed a selection of the most genetically pure Cika individuals as assessed by the panel of microsatellites. These original Cika cattle form an Eastern Alpine breed cluster together with Pinzgauer and Pustertaler cattle. Cika cattle should be considered as an authentic and valuable genetic resource, which offers clear opportunities for sustainable agriculture and landscape conservation in marginal and mountain areas. PMID- 24236612 TI - Rapid biomimetic mineralization of hydroxyapatite-g-PDLLA hybrid microspheres. AB - Hydroxyapatite-graft-poly(D,L-lactide) (HA-g-PDLLA) nanoparticles were synthesized here to fabricate hybrid microspheres with diameter in the range of 150-200 MUm by emulsion solvent evaporation techniques. The as-obtained microspheres were treated with alkaline solution in order to selectively degrade the PDLLA layer which covered on the surface of hybrid microspheres and instead to generate a dense coating of HA nanoparticles. The hybrid microspheres with enriched HA nanoparticles on the surface were further immersed in simulated body fluid (SBF) solution to evaluate the bone-forming ability of the bioactive hybrid microspheres via the in vitro biomimetic mineralization process. The resultant microspheres were analyzed by using X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) to understand the nucleation and growth of bioactive calcium phosphate (Ca-P) crystals as a function of surface treatment. Results in this work clearly demonstrated that the existing HA nanoparticles on the surface of hybrid microspheres after alkaline treatment greatly affect the growth of the bone-like Ca-P crystals in SBF solutions. The biomimetic hybrid microspheres were found to be excellent candidates for use as injectable scaffolds for bone tissue engineering. PMID- 24236613 TI - Virulence and transferability of resistance determinants in a novel Klebsiella pneumoniae sequence type 1137 in China. AB - A study was designed to characterize three carbapenemase-producing Klebsiella pneumoniae isolated from pediatric patients in China. Molecular characterization was done using polymerase chain reaction and sequencing for blaVIM, blaNDM, blaIMP, blaKPC, blaCTX-Ms, blaOXAs, blaTEMs, and blaSHV; plasmid-mediated quinolone resistance determinants; aminoglycoside resistance determinants; multilocus sequencing typing; plasmid replicon typing; addiction; and virulence factors. Kp32 belonged to the newly described sequence type 1137, were positive for aac(6')-Ib-suzhou, qnrA1, qnrB4, qnrS1, aac(6')-Ib, rmtB, armA, blaSHV-12, blaCTX-M-15, blaKPC-2, and blaIMP-4; contained IncA/C plasmids that tested positive for K1 capsular antigens, the ccdAB (coupled cell division locus) addiction system and the wabG, ureA, rmpA, magA, allS, fimH, and the aerobactin virulence factors. However, the others belonged to clone ST11, and were positive for aac(6')-Ib-cr, qnrB4, blaCTX-M-14, blaSHV-11, aac(6')-Ib, rmtB, and blaKPC-2; contained IncFIA plasmids that tested positive for K2 capsular antigens, the vagCD addiction system and the uge, wabG, ureA, kfuBC, rpmA, and fimH virulence factors. ST1137 had more virulence factors than the comparative strains ST11. The blaKPC-2 gene was located on the IncFIA and IncA/C replicon groups of plasmids. An analysis of the genetic environment of blaKPC-2 gene has demonstrated that the blaKPC-2 gene was always associated with one of the Tn4401 isoforms (a or b). Our study suggested that K. pneumoniae carbapenemases being found in virulent K. pneumoniae should be emphasized, as this will eventually become a global health threat. PMID- 24236614 TI - Delicate balance between functionally required flexibility and aggregation risk in a beta-rich protein. AB - Susceptibility to aggregation is general to proteins because of the potential for intermolecular interactions between hydrophobic stretches in their amino acid sequences. Protein aggregation has been implicated in several catastrophic diseases, yet we still lack in-depth understanding about how proteins are channeled to this state. Using a predominantly beta-sheet protein whose folding has been explored in detail, cellular retinoic acid-binding protein 1 (CRABP1), as a model, we have tackled the challenge of understanding the links between a protein's natural tendency to fold, 'breathe', and function with its propensity to misfold and aggregate. We identified near-native dynamic species that lead to aggregation and found that inherent structural fluctuations in the native protein, resulting in opening of the ligand-entry portal, expose hydrophobic residues on the most vulnerable aggregation-prone sequences in CRABP1. CRABP1 and related intracellullar lipid-binding proteins have not been reported to aggregate inside cells, and we speculate that the cellular concentration of their open, aggregation-prone conformations is sufficient for ligand binding but below the critical concentration for aggregation. Our finding provides an example of how nature fine-tunes a delicate balance between protein function, conformational variability, and aggregation vulnerability and implies that with the evolutionary requirement for proteins to fold and function, aggregation becomes an unavoidable but controllable risk. PMID- 24236615 TI - Discovery of two novel beta-glucosidases from an Amazon soil metagenomic library. AB - An Amazon soil microbial community metagenomic fosmid library was functionally screened for beta-glucosidase activity. Contig analysis of positive clones revealed the presence of two ORFs encoding novel beta-glucosidases, AmBGL17 and AmBGL18, from the GH3 and GH1 families, respectively. Both AmBGL17 and AmBGL18 were functionally identified as beta-glucosidases. The enzymatic activity of AmBGL17 was further characterized. AmBGL17 was tested with different substrates and showed highest activity on pNPbetaG substrate with an optimum temperature of 45 degrees C and an optimum pH of 6. AmBGL17 showed a Vmax of 116 mM s(-1) and Km of 0.30 +/- 0.017 mM. This is the first report of beta-glucosidases from an Amazon soil microbial community using a metagenomic approach. PMID- 24236616 TI - Using Mendelian randomization to assess and develop clinical interventions: limitations and benefits. PMID- 24236617 TI - Is sertraline plus transcranial direct current stimulation the future of effective depression treatment? PMID- 24236619 TI - From methods to policy: understanding what works: evaluating the evidence with both eyes open. PMID- 24236620 TI - Interview: comparative effectiveness research and challenges to healthcare reform in the Middle East and USA. PMID- 24236621 TI - Antiretroviral therapy in primary HIV infection. AB - Evaluation of: SPARTAC Trial Investigators, Fidler S, Porter K et al. Short course antiretroviral therapy in primary HIV infection. N. Engl. J. Med. 368, 207 217 (2013). The timing of antiretroviral therapy (ART) in patients who present with primary HIV infection is uncertain. This paper compared three strategies: ART for 48 weeks; ART for 12 weeks; or no therapy in 366 patients with primary HIV infection. They showed that 48 weeks of ART significantly reduced the risk of needing definitive therapy (after a median follow-up of 4.2 years). However, the median delay in needing to start definitive therapy (61 weeks) is not significantly greater than the amount of treatment given (48 weeks) to achieve this result, suggesting that the clinical benefit of immediate ART in primary HIV infection is not yet clear. PMID- 24236622 TI - Strategies for multivessel revascularization in patients with diabetes. AB - Evaluation of: Farkouh ME, Domanski M, Sleeper LA et al. Strategies for multivessel revascularization in patients with diabetes. N. Engl. J. Med. 367, 2375-2384 (2012). The FREEDOM trial enrolled 1900 patients with diabetes and multivessel coronary disease to percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass grafting (CABG). In the drug eluting stents arm, 94% were treated with the first-generation drug-eluting stents. The median duration of follow-up among survivors was 3.8 years. The primary outcome, a composite of death from any cause, nonfatal myocardial infarction or nonfatal stroke, occurred more frequently in the PCI group, with 5 year rates of 26.6% in the PCI group and 18.7% in the CABG group, a statistically significant relative-risk reduction of 30%. Stroke rates were significantly higher in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group. PMID- 24236623 TI - Paying the doctor: evidence-based decisions at the point-of-care and the role of fee-for-service incentives. AB - This article develops a framework for understanding how financial and nonfinancial incentives can complicate point-of-care decision-making by physicians, leading to the overuse or underuse of healthcare services. By examining the types of decisions that clinicians and patients make at the point of-care, the framework clarifies how incentives can distort physicians' decisions about testing, diagnosis and treatment, as well as efforts to enhance patient adherence. The analysis highlights contributing factors that promote and impede evidence-based decision-making, using examples from the 'Choosing Wisely' program. It concludes with a summary of how the existing fee-for-service payment system in the USA may contribute to the problems of over- and under-testing, diagnosis and treatment, highlighted through the efforts of Choosing Wisely. PMID- 24236624 TI - Paying more wisely: effects of payment reforms on evidence-based clinical decision-making. AB - This article reviews the recent research, policy and conceptual literature on the effects of payment policy reforms on evidence-based clinical decision-making by physicians at the point-of-care. Payment reforms include recalibration of existing fee structures in fee-for-service, pay-for-quality, episode-based bundled payment and global payments. The advantages and disadvantages of these reforms are considered in terms of their effects on the use of evidence in clinical decisions made by physicians and their patients related to the diagnosis, testing, treatment and management of disease. The article concludes with a recommended pathway forward for improving current payment incentives to better support evidence-based decision-making. PMID- 24236625 TI - Management options for children with attention-deficit/hyperactivity disorder: a regional perspective on value. AB - Use of comparative effectiveness information in local healthcare decisions can be confounded by variations in practice, barriers to access and population demographics. The New England Comparative Effectiveness Public Advisory Council was convened as a public deliberative panel that considers evidence on the comparative clinical effectiveness and comparative value of a variety of therapeutic interventions. The council is tasked with making summary judgments on the evidence and recommendations for applying the evidence in medical and drug coverage policy, as well as initiating educational efforts for patients and clinicians. The New England Comparative Effectiveness Public Advisory Council met in June 2012 to discuss management options for attention-deficit/hyperactivity disorder, guided by a recent comparative effectiveness review from the Agency for Healthcare Research and Quality and supplementary economic analyses conducted by the Institute for Clinical and Economic Review. This article summarizes the deliberations and reflects on lessons learned regarding use of region-specific economic analyses to guide decision-making. PMID- 24236626 TI - Modernizing the systematic review process to inform comparative effectiveness: tools and methods. AB - Systematic reviews are being increasingly used to inform all levels of healthcare, from bedside decisions to policy-making. Since they are designed to minimize bias and subjectivity, they are a preferred option to assess the comparative effectiveness and safety of healthcare interventions. However, producing systematic reviews and keeping them up-to-date is becoming increasingly onerous for three reasons. First, the body of biomedical literature is expanding exponentially with no indication of slowing down. Second, as systematic reviews gain wide acceptance, they are also being used to address more complex questions (e.g., evaluating the comparative effectiveness of many interventions together rather than focusing only on pairs of interventions). Third, the standards for performing systematic reviews have become substantially more rigorous over time. To address these challenges, we must carefully prioritize the questions that should be addressed by systematic reviews and optimize the processes of research synthesis. In addition to reducing the workload involved in planning and conducting systematic reviews, we also need to make efforts to increase the transparency, reliability and validity of the review process; these aims can be grouped under the umbrella of 'modernization' of the systematic review process. PMID- 24236627 TI - Priority setting for health in emerging markets. AB - The use of health technology assessment research in emerging economies is becoming an increasingly important tool to determine the uses of health spending. As low- and middle-income countries' gross domestic product grows, the funding available for health has increased in tandem. There is growing evidence that comparative effectiveness research and cost-effectiveness can be used to improve health outcomes within a predefined financial space. The use of these evaluation tools, combined with a systematized process of priority setting, can help inform national and global health payers. This review of country institutions for health technology assessment illustrates two points: the efforts underway to use research to inform priorities are widespread and not confined to wealthier countries; and many countries' efforts to create evidence-based policy are incomplete and more country-specific research will be needed. Further evidence shows that there is scope to reduce these gaps and opportunity to support better incorporation of data through better-defined priority-setting processes. PMID- 24236628 TI - Robotic and standard open radical prostatectomy: oncological and quality-of-life outcomes. AB - Prostate cancer is the second leading cause of cancer death among men in the USA. Use of robot-assisted radical prostatectomy (RARP) for the management of localized prostate cancer has increased dramatically in recent years. This review focuses on comparing quality of life following RARP versus retropubic radical prostatectomy. RARP is associated with improved perioperative outcomes, such as reduced blood loss and fewer transfusions. In addition, cancer control after RARP versus retropubic radical prostatectomy is equivalent, with similar incidences of positive surgical margins and comparable early oncological outcomes. RARP appears to provide advantages in recovery of continence, potency and quality of life compared with retropubic radical prostatectomy; however, methodological limitations exist in current literature. PMID- 24236629 TI - Comparative effectiveness of antiarrhythmic drugs on cardiovascular hospitalization and mortality in atrial fibrillation. AB - AIM: To assess, through a systematic review, evidence for the effects of antiarrhythmic drugs (AADs) on cardiovascular (CV) hospitalization and mortality. MATERIALS & METHODS: English language articles were identified using MEDLINE, EMBASE and the Cochrane Clinical Trial Registry and were screened for study applicability and methodological quality. RESULTS: Out of 3526 identified studies, 38 were selected for analysis (19 evaluated individual AADs, 13 compared rate- versus rhythm-control strategies, and 6 evaluated multiple AADs but did not report outcomes for individual agents). None of the studies examining individual AADs employed the CV hospitalization end point used in ATHENA (the reference trial). There were no head-to-head comparisons of individual AADs on CV hospitalization. Most high-quality studies used multidrug rate- versus rhythm control strategies. CONCLUSION: Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence. PMID- 24236630 TI - Engaging hard-to-reach patients in patient-centered outcomes research. AB - AIMS: This study aimed to identify methods to engage hard-to-reach patients in the research process. MATERIALS & METHODS: With funding from the Patient-Centered Outcomes Research Institute (Washington, DC, USA), the University of Maryland (MD, USA) conducted 20 focus groups and one individual interview. The sample consisted of six groups of hard-to-reach patients, two groups of healthcare providers who work with hard-to-reach patients and two groups of surrogates of hard-to-reach patients. RESULTS & CONCLUSION: In order to make patient-centered outcomes research more meaningful to patients and their caregivers, patient centered outcomes research should be conducted with a focus on building and maintaining trust, which is achieved via pre-engagement with communities and continuous engagement of study participants and their communities. PMID- 24236631 TI - Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis. AB - BACKGROUND: Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. AIM: To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. MATERIALS & METHODS: We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. RESULTS: The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. CONCLUSION: Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation. PMID- 24236632 TI - Short-term effectiveness of smoking-cessation treatment on respiratory function and CEA level. AB - AIM: Tobacco smoke contains many chemicals that are harmful and cause carcinogenesis. The aim of this study was to confirm the relationship between smoking and changes in respiratory functional and laboratory parameters comparing, in particular, smoking-cessation treatment's outcomes between smokers who reduce tobacco consumption (reducers) and smokers who quit completely (quitters). MATERIALS & METHODS: A total of 181 current smokers were prospectively enrolled. All of the participants completed a sociodemographic questionnaire and underwent 3 months of varenicline plus nicotine-replacement therapy combined with basic counseling. Laboratory tests and clinical and lung function parameters were evaluated at entry and after 3 months of therapy. After 3 months of smoking-cessation treatment, subjects were sorted into two subgroups: quitters and reducers. RESULTS: After 3 months of combined therapy, 56% of the subjects (101 patients) stopped smoking; the remaining patients reduced. Significant improvements in pulmonary-function tests (especially in the 25-75% forced expiratory volume testing) were recorded. The most significant improvements were obtained in quitters: carboxyhemoglobin was reduced by 1.06%, the average expiratory flow between 25 and 75% of vital capacity increased by 16% from predicted, mean serum CEA level decreased by 1.83 ng/ml, heart rate decreased by approximately 16 beats/min on average and forced 1 s expiratory flow increased by 2.57% from predicted. The Fagerstrom scores showed a positive correlation with the corresponding blood carboxyhemoglobin levels. CONCLUSION: Just 3 months of smoking-cessation treatment achieved significant improvements in lung-function parameters and a decrease in serum CEA, mostly in subjects who totally quit smoking. This result confirms the effectiveness of our smoking cessation treatment and suggests the utility of the selected parameters as tools to motivate and monitor patients. PMID- 24236635 TI - A new flavonoid from the aerial parts of Andrographis paniculata. AB - A new flavonoid, 7,8-dimethoxy-2'-hydroxy-5-O-beta-d-glucopyranosyloxyflavone (1), along with 15 known flavonoids (2-16), was isolated from the aerial parts of Andrographis paniculata Nees. Their structures were elucidated on the basis of chemical and spectroscopic analyses. Most of them have uncommon O-substitution patterns involving 5-, 7-, 8-, 2'-, 3'-, 4'- and 5'-O-substituents. The antiproliferative effects of these flavonoids against human leukaemia HL-60 cells were investigated. Among them, 13 was the most active, displaying potent antiproliferative activity with IC50 of 3.50 MUM. The structure-activity relationships of these isolated compounds were discussed. PMID- 24236636 TI - Mechanism-based inactivation of cytochromes by furan epoxide: unraveling the molecular mechanism. AB - Drugs carrying an unsaturated C?C center (such as furans) form reactive epoxide metabolites and cause irreversible mechanism-based inactivation (MBI) of cytochrome P450 (CYP450) activity, through covalent modification of amino acid residues. Though this reaction is confirmed to take place in the active site of CYPs, the details of the reactions of furan (epoxidation and epoxide ring opening), the conditions under which MBI may occur, the residues involved, the importance of the heme center, etc. have yet to be explored. A density functional theory (DFT) study was carried out (i) to elucidate the reaction pathways for the generation of furan epoxide metabolite from furan ring by the model oxidant Cpd I (iron(IV)-oxo heme-porphine radical cation, to mimic the catalytic domain of CYPs) and (ii) to explore different reactions of the furan epoxide metabolite. The energy profiles of the competitive pathways and the conditions facilitating MBI of CYPs by the reactive epoxide metabolite are reported. The rate-determining step for the overall metabolic pathway leading to MBI was observed to be the initial epoxidation, requiring ~12 kcal/mol under the enzymatic conditions. The covalent adducts (inactivator complexes) are highly stable (~-46 to -70 kcal/mol) and may be formed due to the reaction between furan epoxide and nucleophilic amino acid residues such as serine/threonine, preferably after initial activation by basic amino acids. PMID- 24236637 TI - Dual functions of hypoxia-inducible factor 1 alpha for the commitment of mouse embryonic stem cells toward a neural lineage. AB - Embryonic stem (ES) cells are useful for elucidating the molecular mechanisms of cell fate decision in the early development of mammals. It has been shown that aggregate culture of ES cells efficiently induces neuroectoderm differentiation. However, the molecular mechanism that leads to selective neural differentiation in aggregate culture is not fully understood. Here, we demonstrate that the oxygen-sensitive hypoxia-inducible transcription factor, Hif-1alpha, is an essential regulator for neural commitment of ES cells. We found that a hypoxic environment is spontaneously established in differentiating ES cell aggregates within 3 days, and that this time window coincides with Hif-1alpha activation. In ES cells in adherent culture under hypoxic conditions, Hif-1alpha activation was correlated with significantly greater expression of neural progenitor-specific gene Sox1 compared with ES cells in adherent culture under normoxic conditions. In contrast, Hif-1alpha-depleted ES cell aggregates showed severe reduction in Sox1 expression and maintained high expression of undifferentiated ES cell marker genes and epiblast marker gene Fgf5 on day 4. Notably, chromatin immune precipitation assay and luciferase assay showed that Hif-1alpha might directly activate Sox1 expression. Of additional importance is our finding that attenuation of Hif-1alpha resulted in an increase of BMP4, a potent inhibitor of neural differentiation, and led to a high level of phosphorylated Smad1. Thus, our results indicate that Hif-1alpha acts as a positive regulator of neural commitment by promoting the transition of ES cell differentiation from the epiblast into the neuroectoderm state via direct activation of Sox1 expression and suppressing endogenous BMP signaling. PMID- 24236639 TI - Respiration during sleep in children with therapy-resistant enuresis. AB - AIM: Although there is a known association between enuresis and snoring or sleep apnoeas, respiration during sleep has not been thoroughly studied in enuretic children. This study was performed with the aim of filling this gap in our knowledge. METHODS: Thirty-four children with therapy-resistant enuresis, but no history of heavy snoring or sleep apnoeas, underwent sleep registrations, including standard electroencephalography (EEG) and electrooculography (EOG) as well as registration of oxygen saturation, respiratory effort and nasal air flow. To assess nasal airway patency, rhinomanometry and acoustic rhinometry were performed before and after nasal decongestion. RESULTS: The children were found to have a higher than expected apnoea hypopnoea index (AHI), due to a high frequency of hypopnoeas. They were also noted to have a tendency for respiratory arousals. Standard polysomnographic variables were normal. CONCLUSION: We provide baseline data of nocturnal respiration in enuretic children. The children were found to have subclinical signs of disordered respiration. This may be one of the explanations for their high arousal thresholds. PMID- 24236640 TI - The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels. AB - ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in iron metabolism is not known. ATOH8 expression in HEK293 cells resulted in increased endogenous HAMP mRNA levels as well as HAMP promoter activity. Mutation of the E-box or SMAD response elements within the HAMP promoter significantly reduced the effects of ATOH8, indicating that ATOH8 activates HAMP transcription directly as well as through bone morphogenic protein (BMP) signalling. In support of the former, Chromatin immunoprecipitation assays provided evidence that ATOH8 binds to E-box regions within the HAMP promoter while the latter was supported by the finding that ATOH8 expression in HEK293 cells led to increased phosphorylated SMAD1,5,8 levels. Liver Atoh8 levels were reduced in mice under conditions associated with increased erythropoietic activity such as hypoxia, haemolytic anaemia, hypotransferrinaemia and erythropoietin treatment and increased by inhibitors of erythropoiesis. Hepatic Atoh8 mRNA levels increased in mice treated with holo transferrin, suggesting that Atoh8 responds to changes in plasma iron. ATOH8 is therefore a novel transcriptional regulator of HAMP, which is responsive to changes in plasma iron and erythroid activity and could explain how changes in erythroid activity lead to regulation of HAMP. PMID- 24236642 TI - A systematic review of the factors associated with interest in predictive genetic testing for obesity, type II diabetes and heart disease. AB - BACKGROUND: In the future, it may be possible for individuals to take a genetic test to determine their genetic predisposition towards developing lifestyle related chronic diseases. A systematic review of the literature was undertaken to identify the factors associated with an interest in having predictive genetic testing for obesity, type II diabetes and heart disease amongst unaffected adults. METHODS: Ovid Medline, PsycINFO and EMBASE online databases were searched using predefined search terms. Publications meeting the inclusion criteria (English language, free-living adult population not selected as a result of their disease diagnosis, reporting interest as an outcome, not related to a single gene inherited disease) were assessed for quality and content. Narrative synthesis of the results was undertaken. RESULTS: From the 2329 publications retrieved, eight studies met the inclusion criteria and were included in the review. Overall, the evidence base was small but of positive quality. Interest was associated with personal attitudes towards disease risk and the provision of information about genetic testing, shaped by perceived risk of disease and expected outcomes of testing. The role of demographic factors was investigated with largely inconclusive findings. CONCLUSIONS: Interest in predictive genetic testing for obesity, type II diabetes or heart disease was greatest amongst those who perceived the risk of disease to be high and/or the outcomes of testing to be beneficial. PMID- 24236638 TI - Physiological and environmental control of yeast prions. AB - Prions are self-perpetuating protein isoforms that cause fatal and incurable neurodegenerative disease in mammals. Recent evidence indicates that a majority of human proteins involved in amyloid and neural inclusion disorders possess at least some prion properties. In lower eukaryotes, such as yeast, prions act as epigenetic elements, which increase phenotypic diversity by altering a range of cellular processes. While some yeast prions are clearly pathogenic, it is also postulated that prion formation could be beneficial in variable environmental conditions. Yeast and mammalian prions have similar molecular properties. Crucial cellular factors and conditions influencing prion formation and propagation were uncovered in the yeast models. Stress-related chaperones, protein quality control deposits, degradation pathways, and cytoskeletal networks control prion formation and propagation in yeast. Environmental stresses trigger prion formation and loss, supposedly acting via influencing intracellular concentrations of the prion inducing proteins, and/or by localizing prionogenic proteins to the prion induction sites via heterologous ancillary helpers. Physiological and environmental modulation of yeast prions points to new opportunities for pharmacological intervention and/or prophylactic measures targeting general cellular systems rather than the properties of individual amyloids and prions. PMID- 24236643 TI - HNA-3 gene frequencies in Brazilians and a new polymerase chain reaction restriction fragment length polymorphism method for HNA-3a/3b genotyping. AB - BACKGROUND: HNA-3 antigens are the result of a rs2288904 single-nucleotide polymorphism (SNP) in the CTL2, and the HNA-3a and HNA-3b variants are encoded by a guanine and adenine at Nucleotide Position 461. Anti-HNA-3 are involved in severe transfusion-related acute lung injury reactions and in neonatal alloimmune neutropenia. Since the distribution of the HNA-3 system was unknown in South Americans, in this study we determined the frequency of the HNA-3 alleles in Brazilians. STUDY DESIGN AND METHODS: DNA of 500 blood donors, 120 Xikrin Amerindians, 74 Japanese individuals, and 124 African Brazilians were genotyped for rs2288904 by a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. The PCR product was digested with enzyme Taq(alpha) 1, specific to nucleotide guanine (HNA-3a). RESULTS: The results showed that the frequencies of the HNA-3a/HNA-3b alleles were 0.81/0.19 in blood donors, 1.00/0.00 in Amerindians, 0.63/0.37 in Japanese, and 0.85/0.15 in African Brazilians. All 81 individuals genotyped as HNA-3a/a did not present the SNP c.457T by molecular sequencing. CONCLUSION: The frequencies of HNA-3 genotypes in Brazilian blood donors is similar to that described in Caucasians; however, all Amerindians were HNA-3a/a, African Brazilians showed a lower frequency of HNA 3b/b, and Japanese had a higher prevalence of HNA-3b/b, suggesting that they may be at risk for developing anti-HNA-3a alloantibodies. PMID- 24236645 TI - Heritabilities and genetic correlations between fetlock, hock and stifle osteochondrosis and fetlock osteochondral fragments in Hanoverian Warmblood horses. AB - The main objective of this study is to estimate genetic parameters for osteochondrosis (OC) and osteochondrosis dissecans (OCD) in fetlock, hock and stifle joints as well as for palmar or plantar osteochondral fragments (POFs) and dorsodistal osteochondral fragments (DOFs) in fetlock joints. For this purpose, the results of a standardized radiographic examination of 7396 Hanoverian Warmblood horses were used. Heritabilities and genetic correlations were estimated using residual maximum likelihood (REML) under a linear animal model. Heritability estimates for OC at the different joints were at 0.17-0.34, for OCD at 0.16-0.46, for POFs at 0.19 and for DOFs at 0.22 after transformation onto the liability scale. For osteochondral fragments (OFs), lower heritabilities were estimated, especially in fetlock joints. POFs were genetically negatively correlated with OC in each joint. The size of the heritability estimates indicates that the prevalence of these radiographic findings can be reduced by breeding measures. However, differentiation among the different clinical entities is crucial to avoid underestimation of heritabilities. The analysis of genetic parameters performed in this study indicates that OC and OCD in fetlock, OC and OCD in hock, OC and OCD in stifle joints, POFs of the hindlimbs and DOFs may be treated as different traits. PMID- 24236644 TI - Corticomedullary differentiation and maturational arrest in thymomas. AB - AIMS: Morphological complexity hampers the histological classification of thymomas. Our aim was to determine whether the use of novel differentiation and maturation markers of cortical and medullary thymic epithelial cells (cTECs and mTECs) might provide an approach to understanding the underlying biology of these tumours. METHODS AND RESULTS: Fifty-seven thymomas were studied by immunohistochemistry. The cortical markers used were B5T, PRSS16, and cathepsin V. The medullary markers used were CD40, claudin-4, AIRE, and desmin. Involucrin and cytokeratin 10 were used to study terminal mTEC maturation. Irrespective of histological subtype, most thymomas contained distinct areas with cortical and medullary differentiation. Type B1, type B2 and type AB thymomas showed marked bi lineage differentiation, with lack of terminal mTEC maturation in type AB. Type AB thymomas were unique in showing areas where cells with either cortical or medullary differentiation were intimately 'mixed' at the single-cell level. Type B3 and type A thymomas showed only abortive lineage differentiation and maturation. CONCLUSIONS: Thymomas show highly characteristic patterns of bi lineage TEC differentiation that reflect the histological subtypes recognized by the WHO classification. We hypothesize that thymomas arise from thymic precursor cells with different cortical and/or medullary maturation defects. PMID- 24236646 TI - Increased dairy consumption differentially improves metabolic syndrome markers in male and female adults. AB - BACKGROUND: Effects of dairy consumption on metabolic health and adiposity are inconsistent. Most clinical trials have investigated dairy intake, frequently during caloric restriction, in overweight or obese populations but not in a metabolic syndrome population. We investigated the effect of increased dairy intake without caloric restriction on anthropometrics, plasma lipids, and glucose in typically low-dairy consumers who met the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) metabolic syndrome criteria. METHODS: Male (n=14) and female (n=23) adults (54.1 +/- 9.7 years) with metabolic syndrome were randomized to consume low-fat dairy (LFD) (10 oz of 1% milk, 6 oz of nonfat yogurt, 4 oz of 2% cheese) or carbohydrate control (CNT) (1.5-oz granola bar and 12 oz of 100% juice) foods for 6 weeks in a crossover study design. Anthropometrics, metabolic syndrome parameters, insulin resistance, and parathyroid hormone were measured. Body composition was analyzed by a dual-energy X-ray absorptiometry scan for a subset of subjects (n=22). RESULTS: LFD modulated metabolic syndrome parameters differently according to gender. Following LFD, men had lower glucose (95.4 +/- 9.1 vs. 98.9 +/- 10.6 mg/dL, P=0.048), whereas women had lower body weight (BW), waist circumference, and body mass index (P<0.01) compared to CNT. Women also had lower energy intake following LFD compared to CNT. Increases in phosphorus (a dairy nutrient) were negatively correlated with decreases in BW (r=-0.537; P<0.01) and body fat in women (r=-0.593, P<0.025), whereas the decreases in energy intake had no correlation with anthropometrics. CONCLUSIONS: Three dairy servings/day promoted small but significant improvements differentially by gender in a metabolic syndrome population. PMID- 24236647 TI - The onset of childhood amnesia in childhood: a prospective investigation of the course and determinants of forgetting of early-life events. AB - The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children aged 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children aged 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID- 24236648 TI - Immunosuppression for pancreas transplantation with an emphasis on antibody induction strategies: review and perspective. AB - A review of recent literature was performed to identify trends and evaluate outcomes with respect to immunosuppression in pancreas transplantation (PTX). In the past decade, the majority of PTXs were performed with depleting antibody induction, particularly in the setting of either calcineurin inhibitor minimization, corticosteroid withdrawal or both. Maintenance immunosuppression consisted of predominantly tacrolimus (TAC)/mycophenolatemofetil, TAC/mycophenolic acid or TAC/sirolimus with or without corticosteroids. Depending on PTX category, donor and recipient risk factors, case mix and immunosuppressive regimen, the 1-year incidence of acute rejection has decreased to 5-20%. Current 1-year rates of immunological pancreas graft loss range between 1.8 and 6%. Depleting antibody induction and either TAC/mycophenolatemofetil or TAC/sirolimus maintenance therapy with early steroid withdrawal have become the mainstay of immunosuppression in PTX. However, the development of non-nephrotoxic, nondiabetogenic, and nongastrointestinal toxic regimens is highly desirable to improve quality of life in all solid organ transplant recipients. PMID- 24236649 TI - Study on human intestinal bacterium Blautia sp. AUH-JLD56 for the conversion of arctigenin to (-)-3'-desmethylarctigenin. AB - Arctium lappa L. (A. lappa) is a popularly used vegetable as well as herbal medicine. Human intestinal microflora was reported to convert arctiin, the lignan compound with highest content in the dried fruits of Arctium lappa, to a series of metabolites. However, the specific bacterium responsible for the formation of 3'-desmethylarctigenin (3'-DMAG), the most predominant metabolite of arctiin by rat or human intestinal microflora, has not been isolated yet. In the present study, we isolated one single bacterium, which we named Blautia sp. AUH-JLD56, capable of solely biotransforming arctiin or arctigenin to (-)-3'-DMAG. The structure of the metabolite 3'-DMAG was elucidated by electrospray ionization mass spectrometry (ESI-MS) and (1)H and (13)C nuclear magnetic resonance spectroscopy. The biotransforming kinetics and maximum biotransforming capacity of strain AUH-JLD56 was investigated. In addition, the metabolite 3'-DMAG showed significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than that of the substrate arctigenin at the concentrations tested. PMID- 24236650 TI - Characterization of amyloid formation by glucagon-like peptides: role of basic residues in heparin-mediated aggregation. AB - Glycosaminoglycans (GAGs) have been reported to play a significant role in amyloid formation of a wide range of proteins/peptides either associated with diseases or native biological functions. The exact mechanism by which GAGs influence amyloid formation is not clearly understood. Here, we studied two closely related peptides, glucagon-like peptide 1 (GLP1) and glucagon-like peptide 2 (GLP2), for their amyloid formation in the presence and absence of the representative GAG heparin using various biophysical and computational approaches. We show that the aggregation and amyloid formation by these peptides follow distinct mechanisms: GLP1 follows nucleation-dependent aggregation, whereas GLP2 forms amyloids without any significant lag time. Investigating the role of heparin, we also found that heparin interacts with GLP1, accelerates its aggregation, and gets incorporated within its amyloid fibrils. In contrast, heparin neither affects the aggregation kinetics of GLP2 nor gets embedded within its fibrils. Furthermore, we found that heparin preferentially influences the stability of the GLP1 fibrils over GLP2 fibrils. To understand the specific nature of the interaction of heparin with GLP1 and GLP2, we performed all-atom MD simulations. Our in silico results show that the basic-nonbasic-basic (B-X-B) motif of GLP1 (K28-G29-R30) facilitates the interaction between heparin and peptide monomers. However, the absence of such a motif in GLP2 could be the reason for a significantly lower strength of interaction between GLP2 and heparin. Our study not only helps to understand the role of heparin in inducing protein aggregation but also provides insight into the nature of heparin-protein interaction. PMID- 24236651 TI - Cerebral vascular malformations in hereditary hemorrhagic telangiectasia. AB - OBJECT: Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disorder characterized by mucocutaneous telangiectasias, frequent nosebleeds, and visceral arteriovenous malformations (AVMs). Few reports have outlined the prevalence of the various cerebral vascular malformations found in patients with HHT. The authors set out to define the prevalence of cerebral vascular malformations in a population of HHT patients who underwent imaging with 3-T imaging (MRI/MR angiography [MRA]) of the brain. METHODS: A retrospective review of prospectively collected data was carried out using a database of 372 HHT patients who were seen and examined at the Georgia Regents University HHT Center and screened with 3-T MRI/MRA. Data were tabulated for numbers and types of vascular malformations in this population. RESULTS: Arteriovenous malformations were identified in 7.7%, developmental venous anomalies in 4.3%, and cerebral aneurysms in 2.4% of HHT patients. The HHT AVMs tended to be supratentorial, small, and cortical in this series, findings consistent with other recent studies in the literature. An arteriovenous fistula, cavernous malformation, and capillary telangiectasia were identified in 0.5%, 1%, and 1.9% of HHT patients, respectively. CONCLUSIONS: Few studies have investigated the prevalence of the various vascular malformations found in HHT patients screened with 3-T MRI/MRA of the brain. Hereditary hemorrhagic telangiectasia AVMs are more likely to be multiple and have a tendency toward small size and cortical location. As such, they are often treated using a single-modality therapy. PMID- 24236653 TI - Molecular genetics of paragangliomas of the skull base and head and neck region: implications for medical and surgical management. AB - Paragangliomas are rare, slow-growing tumors that frequently arise in the head and neck, with the carotid bodies and temporal bone of the skull base being the most common sites. These neoplasms are histologically similar to pheochromocytomas that form in the adrenal medulla and are divided into sympathetic and parasympathetic subtypes based on functionality. Skull base and head and neck region paragangliomas (SHN-PGs) are almost always derived from parasympathetic tissue and rarely secrete catecholamines. However, they can cause significant morbidity by mass effect on various cranial nerves and major blood vessels. While surgery for SHN-PG can be curative, postoperative deficits and recurrences make these lesions challenging to manage. Multiple familial syndromes predisposing individuals to development of paragangliomas have been identified, all involving mutations in the succinate dehydrogenase complex of mitochondria. Mutations in this enzyme lead to a state of "pseudohypoxia" that upregulates various angiogenic, survival, and proliferation factors. Moreover, familial paraganglioma syndromes are among the rare inherited diseases in which genomic imprinting occurs. Recent advances in gene arrays and transcriptome/exome sequencing have identified an alternate mutation in sporadic SHN-PG, which regulates proto-oncogenic pathways independent of pseudohypoxia-induced factors. Collectively these findings demonstrate that paragangliomas of the skull base and head and neck region have a distinct genetic signature from sympathetic-based paragangliomas occurring below the neck, such as pheochromocytomas. Paragangliomas serve as a unique model of primarily surgically treated neoplasms whose future will be altered by the elucidation of their genomic complexities. In this review, the authors present an analysis of the molecular genetics of SHN-PG and provide future directions in patient care and the development of novel therapies. PMID- 24236652 TI - Lesion analysis for cingulotomy and limbic leucotomy: comparison and correlation with clinical outcomes. AB - OBJECT: Cingulotomy and limbic leucotomy are lesioning surgeries with demonstrated benefit for medically intractable psychiatric illnesses. They represent significant refinements of the prefrontal lobotomy used from the 1930s through the 1950s. However, the associations between anatomical characterization of these lesions and outcome data are not well understood. To elucidate these procedures and associations, the authors sought to define and compare the neuroanatomy of cingulotomy and limbic leucotomy and to test a method that uses neuroanatomical data and voxel-based lesion-symptom mapping (VLSM) to reveal potential refinements to modern psychiatric neurosurgical procedures. METHODS: T1 weighted MR images of patients who had undergone cingulotomy and limbic leucotomy were segmented and registered onto the Montreal Neurological Institute T1 weighted template brain MNI152. Using an atlas-based approach, the authors calculated, by case, the percentage of each anatomical structure affected by the lesion. Because of the infrequency of modern lesion procedures and the requirement for higher-resolution clinical imaging, the sample size was small. The pilot study correlated cingulotomy and limbic leucotomy lesion characteristics with clinical outcomes for patients with obsessive-compulsive disorder. For this study, preoperative and postoperative Yale-Brown Obsessive Compulsive Scale scores for 11 cingulotomy patients and 8 limbic leucotomy patients were obtained, and lesion masks were defined and compared anatomically by using an atlas-based method. Statistically significant voxels were additionally calculated by using VLSM techniques that correlated lesion characteristics with postoperative scores. RESULTS: Mean lesion volumes were 13.3 ml for cingulotomy and 11.8 ml for limbic leucotomy. As expected, cingulotomy was isolated to the anterior cingulum. The subcaudate tractotomy portion of limbic leucotomy additionally affected Brodmann area 25, the medial orbitofrontal cortex, and the nucleus accumbens. Initial results indicated that the dorsolateral regions of the cingulotomy lesion and the posteroventral regions of the subcaudate tractotomy lesion were associated with improved postoperative Yale Brown Obsessive Compulsive Scale scores. CONCLUSIONS: Cingulotomy and limbic leucotomy are lesioning surgeries that target pathological circuits implicated in psychiatric disease. Lesion analysis and VLSM contextualize outcome data and have the potential to be useful for improving lesioning neurosurgical procedures. PMID- 24236654 TI - Surgery for insular low-grade glioma: predictors of postoperative seizure outcome. AB - OBJECT: Although a number of recent studies on the surgical treatment of insular low-grade glioma (LGG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG. METHODS: The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor's infiltrative pattern quantified by computing the difference between the preoperative T2- and T1-weighted MR images (DeltaVT2T1) in 52 patients with preoperative drug-resistant epilepsy. RESULTS: The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR >= 90% (p < 0.001) and DeltaVT2T1 < 30 cm(3) (p < 0.001). In the final model, DeltaVT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001). CONCLUSIONS: No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high DeltaVT2T1 values, which consequently reflects a smaller EOR. PMID- 24236655 TI - Pure arterial malformations of the posterior cerebral artery. PMID- 24236656 TI - Cerebrospinal fluid leak. PMID- 24236657 TI - Risks of common complications in deep brain stimulation surgery: management and avoidance. AB - OBJECT: Deep brain stimulation (DBS) surgery is increasingly prominent in the treatment of various disorders refractory to medication. Despite the procedure's efficacy, the community at large continues to be hesitant about presumed associated risks. The main object of this study was to assess the incidence of various surgical complications occurring both during and after DBS device implantation in a large population of patients with movement disorders in an effort to better quantify patient risk, define management plans, and develop methods for risk avoidance. A second aim was to corroborate the low procedural complication risk of DBS reported by others, which in light of the procedure's efficacy is needed to promote its widespread acceptance. METHODS: All patients who had undergone new DBS device implantation surgery between 2002 and 2010 by a single surgeon were entered into a database after being verified by cross referencing manufacturer implantation records. All surgical records and charts were reviewed to identify intraoperative, perioperative, and long-term surgical complications, including any characteristics predictive of an adverse event. RESULTS: Seven hundred twenty-eight patients received 1333 new DBS electrodes and 1218 new internal pulse generators (IPGs) in a total of 1356 stereotactic procedures for the treatment of movement disorders. Seventy-eight percent of the patients had staged lead and IPG implantations. Of the 728 patients, 452 suffered from medically refractory Parkinson disease; in the other patients, essential tremor (144), dystonia (64), mixed disease (30), and other hyperkinetic movement disorders (38) were diagnosed. Severe intraoperative adverse events included vasovagal response in 6 patients (0.8%), hypotension in 2 (0.3%), and seizure in 2 (0.3%). Postoperative imaging confirmed asymptomatic intracerebral hemorrhage (ICH) in 4 patients (0.5%), asymptomatic intraventricular hemorrhage in 25 (3.4%), symptomatic ICH in 8 (1.1%), and ischemic infarction in 3 (0.4%), associated with hemiparesis and/or decreased consciousness in 13 (1.7%). Long term complications of DBS device implantation not requiring additional surgery included hardware discomfort in 8 patients (1.1%) and loss of desired effect in 10 (1.4%). Hardware-related complications requiring surgical revision included wound infections in 13 patients (1.7%), lead malposition and/or migration in 13 (1.7%), component fracture in 10 (1.4%), component malfunction in 4 (0.5%), and loss of effect in 19 (2.6%). CONCLUSIONS: The authors confirmed that the overall risk of both procedure- and hardware-related adverse events is acceptably low. They offer advice on how to avoid the most common complications. PMID- 24236658 TI - Decompressive craniectomy. PMID- 24236659 TI - Complications with cranial perforators. PMID- 24236660 TI - Surgical outcomes of the minimum anterior and posterior combined transpetrosal approach for resection of retrochiasmatic craniopharyngiomas with complicated conditions. AB - OBJECT: Retrochiasmatic craniopharyngiomas are surgically challenging tumors. Retrochiasmatic craniopharyngiomas with complicated conditions such as large diameter, major calcification, or significant extension to the third ventricle or posterior fossa present surgical challenges; moreover, recurrent retrochiasmatic craniopharyngiomas are particularly formidable challenges. Although the transpetrosal approach to retrochiasmatic craniopharyngiomas published by Hakuba in 1985 can provide unique advantageous exposure of the retrochiasmatic area to allow safe neurovascular dissection and facilitate radical tumor removal, the procedure is viewed as complicated and time consuming and has a high risk of damaging hearing functions. The authors have modified Hakuba's technique to minimize petrosectomy and reduce surgical complications and have applied this modified approach to retrochiasmatic craniopharyngiomas with complicated conditions. In this study, the authors describe their technique and surgical outcomes to elucidate the role of this modified transpetrosal approach for retrochiasmatic craniopharyngiomas with complicated conditions. This is the first study to report surgical outcomes of the transpetrosal approach for retrochiasmatic craniopharyngiomas. METHODS: Between 1999 and 2011, the minimum anterior and posterior combined (MAPC) transpetrosal approach, which is a modification of Hakuba's transpetrosal approach, was applied in 16 cases of retrochiasmatic craniopharyngiomas with complicated conditions. Eight cases were recurrent tumors, 4 had previously received radiotherapy, 11 had a large diameter, 10 had large calcification, 15 had superior extension of the tumor into the third ventricle, and 10 had a posterior extension of the tumor that compressed the midbrain and pons. In all 16 patients, more than 2 of these complicated conditions were present. The follow-up duration ranged from 0.8 to 12.5 years (mean 5.3 years). Surgical outcomes assessed were the extent of resection, surgical complications, visual function, endocrinological status, and neuropsychological function. Five-year and 10-year recurrence-free survival rates were also calculated. RESULTS: Gross-total or near-total resection was achieved in 15 cases (93.8%). Facial nerve function was completely maintained in all 16 patients. Serviceable hearing was preserved in 15 cases (93.8%). Visual function improved in 13 out of 14 cases (92.9%) that had visual disturbance before surgery. None of the patients experienced deterioration of their visual function. Twelve cases had endocrinological deficit and received hormonal replacement before surgery. New endocrinological deficit occurred in 2 cases (12.5%). Neuropsychological function was maintained in 14 cases (87.5%) and improved in 1 case (6.3%). One case that had received previous conventional radiotherapy treatment showed a gradual decline in neuropsychological function. The 5-year and 10-year recurrence-free survival rates were both 86.5%. CONCLUSIONS: The authors obtained good results by using the MAPC transpetrosal approach for the removal of retrochiasmatic craniopharyngiomas with complicated conditions. The MAPC transpetrosal approach should be considered as a therapeutic option for selected cases of retrochiasmatic craniopharyngiomas with complicated conditions. PMID- 24236661 TI - Hyperglycaemia in pregnancy: what's in a name? PMID- 24236662 TI - Use of circulating tumor cell technology (CELLSEARCH) for the diagnosis of malignant pleural effusions. AB - RATIONALE: Cytological analysis of pleural effusions (PEs) has a sensitivity of approximately 60%. We hypothesized that the CELLSEARCH technology (Janssen Research and Development, Huntingdon Valley, PA) currently used to detect circulating tumor cells could be adapted for the identification of tumor cells in PEs. METHODS: This was a single-center, prospective, observational study. Pleural fluid from subjects with undiagnosed PEs were analyzed by CELLSEARCH technology, which uses an epithelial cell adhesion molecule antibody-based capture system/cytokeratin antibodies to identify tumor cells. Subjects were prospectively monitored by periodic chart review to determine the etiology of the PE. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two subjects were analyzed. A malignant etiology was established in 81 subjects. The median number of "positive" pleural epithelial cells (PECs) detected per milliliter of pleural fluid was 6 in the benign group. The number of PECs was 52 in the malignant nonepithelial group (NS) and 526 in the malignant epithelial group (P < 0.001). Unlike blood, there was a baseline number of "positive" cells in benign pleural fluids; however, any cutoff greater than 852 positive cells/ml had 100% specificity. The area under the receiver operating characteristic curve was 0.86. Nine percent of our cancer cases had high numbers of PECs (>280/ml) but a negative or nondefinitive cancer diagnosis by cytology. CONCLUSIONS: The pleural CELLSEARCH assay may serve as a valuable addition to traditional cytology and provide useful information regarding the diagnosis of malignant effusions. Major advantages include that it is well standardized, relatively inexpensive, has a rapid turnaround, and is easily available. Our data support the conduct of additional studies of this approach to assist in the diagnosis of malignant PEs. PMID- 24236663 TI - Personality traits and personality disorders in older women: an explorative study between normal development and psychopathology. AB - The relationships between Axis II personality disorders (DSM-IV) and the Five Factor Model (FFM) were explored in older women. The sample consists of 90 participants (M = 72.29 years, SD = 7.10) who were administered the NEO-Five Factor Inventory and the Personality Diagnostic Questionnaire. The highest prevalence of A and C clusters and obsessive-compulsive personality disorder was observed. Also, elevated neuroticism and decreased agreeableness and openness appear as valuable traits in the description of psychopathology. The study of maladaptive personality functioning within an aging population can be described with the same traits that underlie normal personality functioning, extending the range of psychopathology to a dimensional approach. PMID- 24236664 TI - A 38 nt region and its flanking sequences within gag of Friend murine leukemia virus are crucial for splicing at the correct 5' and 3' splice sites. AB - The genome of the Friend murine leukemia virus (Fr-MLV) contains a 5' splice site (5'ss) located at 205 nt and a 3'ss located at 5489 nt. In our previous studies, it was shown that if the HindIII-BglII (879-1904 bp) fragment within gag is deleted from the proA8m1 vector, which carries the entire Fr-MLV sequence, then cryptic splicing of env-mRNA occurs. Here, attempts were made to identify the genomic segment(s) in this region that is/are essential to correct splicing. First, vectors with a serially truncated HindIII-BglII fragment were constructed. The vector, in which a 38 bp fragment (1612-1649 bp) is deleted or reversed in proA8m1, only produced splice variants. It was found that a 38 nt region within gag contains important elements that positively regulate splicing at the correct splice sites. Further analyses of a series of vectors carrying the 38 bp fragment and its flanking sequences showed that a region (1183-1611 nt) upstream of the 38 nt fragment also contains sequences that positively or negatively influence splicing at the correct splice sites. The SphI-NdeI (5140-5400 bp) fragment just upstream of the 3'ss was deleted from vectors that carried the 38 bp fragment and its flanking sequences, which yielded correctly spliced mRNA; interestingly, these deleted vectors showed cryptic splicing. These findings suggest that the 5140-5400 nt region located just upstream of the 3'ss is required for the splicing function of the 38 nt fragment and its flanking sequences. PMID- 24236665 TI - Fertility and sexual function in long-term survivors of haematological malignancy: using patient-reported outcome measures to assess a neglected area of need in the late effects clinic. AB - Problems of sexual function and fertility in long-term survivors (>=5 years) of haematological malignancy are often neglected in clinic. Our centre carried out a questionnaire study in this population addressing patient-perceived fertility and sexual function. 718 patients responded (56% of those invited; 39% Hodgkin, 45% non-Hodgkin lymphoma, 16% acute leukaemia). Respondent women were more likely to remain childless than a normal control population. Self-reported infertility was more likely in men than women [odds ratio (OR) 1.77, P = 0.001]. Myeloablative therapy increased the likelihood of childlessness (OR 2.48, P = 0.004). Few attended fertility support services (12%). 24% of men banked sperm and 29% of these used the sample, of which 46% resulted in successful pregnancy. Fertility clinic attendance and sperm storage was more likely post-1990 (OR 4.05, P < 0.001; OR 5.05, P < 0.001 respectively). Reporting a negative impact of cancer on sexual function was more common in women than men (OR 2.20, P < 0.001), and increased with current age and age at diagnosis (by 3-4% per year, P <= 0.001) but decreased with longer follow-up (by 2%/year, P = 0.005). Patients on anti depressants and those reporting cancer-related body change/appearance concerns more frequently reported a negative impact (P < 0.04 and P < 0.03 respectively). These self-reported outcomes confirm literature findings, suggest improvement over time, but highlight a need for involvement of support services. PMID- 24236666 TI - Noncontiguous lumbar vertebral hemangiomas treated by posterior decompression, intraoperative kyphoplasty, and segmental fixation. AB - Vertebral hemangiomas are benign lesions and are often asymptomatic. Most vertebral hemangiomas that cause cord compression and neurological symptoms are located in the thoracic spine and involve a single vertebra. The authors report the rare case of lumbar hemangiomas in a 60-year-old woman presenting with severe back pain and rapidly progressive neurological signs attributable to 2 noncontiguous lesions. After embolization of the feeding arteries, no improvement was noted. Thus, the authors performed open surgery using a combination of posterior decompression, intraoperative kyphoplasty, and segmental fixation. The patient experienced relief from back and leg pain immediately after surgery. At 3 months postoperatively, her symptoms and neurological deficits had improved completely. To the authors' knowledge, this is the first description of 2 noncontiguous extensive lumbar hemangiomas presenting with neurological symptoms managed by such combined treatment. The combined management seems to be an effective method for treating symptomatic vertebral hemangiomas. PMID- 24236667 TI - Unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach compared with conventional bilateral pedicle screw fixation for single segment degenerative lumbar instability: a prospective randomized study. AB - OBJECT: Treatment of patients with single-segment degenerative lumbar instability using unilateral pedicle screw fixation can achieve stability and fusion rates similar to those of bilateral pedicle screw fixation. The aim of this study was to analyze the clinical outcome of using unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach to treat single-segment degenerative lumbar instability. METHODS: Thirty-nine consecutive patients with single-segment, low-grade, degenerative lumbar instability were randomly assigned to treatment with either unilateral (n = 20) or bilateral (n = 19) pedicle screw fixation. In the unilateral group, patients underwent unilateral posterior lumbar interbody fusion (PLIF) and ipsilateral pedicle screw fixation through a tubular retractor via the Wiltse approach. In the bilateral group, patients underwent modified bilateral PLIF with bilateral pedicle screw fixation via the posterior midline approach. During follow-up, patients were evaluated using a visual analog scale (VAS), the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index. RESULTS: The unilateral group had a shorter operative duration (p < 0.05) and less blood loss (p < 0.001). All patients completed more than 2 years of follow-up (mean 36 months). In general, the time trends in improvement on the VAS and JOA differed slightly between the groups through 2 years, but no significant difference in back pain VAS score or leg pain VAS score was found between these 2 groups at the 2-year follow-up. Complete bone fusion was shown on CT in all patients at the 2-year follow-up. CONCLUSIONS: Unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach appears to be as safe and effective as bilateral pedicle screw fixation for the treatment of single-segment degenerative lumbar instability. PMID- 24236668 TI - Spine surgery referrals redirected through a multidisciplinary care pathway: effects of nonsurgeon triage including MRI utilization. AB - OBJECT: The Saskatchewan Spine Pathway (SSP) was introduced to improve quality and access to care for patients with low-back and leg pain in the province. There is very limited data regarding the efficacy of nonsurgeon triage of surgical referrals. The objective of this early implementation study was to determine how the SSP affects utilization of MRI and spine surgery. METHODS: The authors performed a retrospective analysis of 87 consecutive patients with low-back and leg pain who were initially referred to a spine surgeon but were instead redirected to the SSP clinic between May 1, 2011, and November 30, 2011. The SSP clinic triaged patients into 2 groups: Group A (nonsurgical management) and Group B (referred back to the spine surgeon). The SSP classification was modified from the classification proposed by Hall et al. Pain and disability were scored by pain-related visual analog scale, modified Oswestry Disability Index, and EuroQol 5D. RESULTS: Sixty-two patients (Group A, 71.3%) were discharged after patient education, self-care advice, and/or referral for additional mechanical therapies. Although only 25 patients (Group B, 28.7%) were directed back to the surgeon, the final percentage (12.6%) offered surgery was similar to that of historic controls (15%). Total MRI utilization was significantly lower in Group A (25.8%) than Group B (92.0%) (p < 0.0001). Nonsurgeon triage captured all red flags detected by the surgeon. Patients in Group B were much more likely to have a leg-dominant pain (p = 0.0088) and had significantly higher Oswestry Disability Index (p = 0.0121) and EuroQol-5D mobility (p = 0.0484) scores. CONCLUSIONS: The SSP significantly reduced MRI utilization and referrals seen by the surgeon for nonoperative care. Although this early implementation study suggests potential for cost savings, a more rigorous analysis of outcomes, costs, and patient satisfaction is required. PMID- 24236669 TI - A new alarm point of transcranial electrical stimulation motor evoked potentials for intraoperative spinal cord monitoring: a prospective multicenter study from the Spinal Cord Monitoring Working Group of the Japanese Society for Spine Surgery and Related Research. AB - OBJECT: Although multimodal intraoperative spinal cord monitoring provides greater accuracy, transcranial electrical stimulation motor evoked potential (TcMEP) monitoring became the gold standard for intraoperative spinal cord monitoring. However, there is no definite alarm point for TcMEPs because a multicenter study is lacking. Thus, based on their experience with 48 true positive cases (that is, a decrease in potentials followed by a new neurological motor deficit postoperatively) encountered between 2007 and 2009, the authors set a 70% decrease in amplitude as the alarm point for TcMEPs. METHODS: A total of 959 cases of spinal deformity, spinal cord tumor, and ossification of the posterior longitudinal ligament (OPLL) treated between 2010 and 2012 are included in this prospective multicenter study (18 institutions). These institutions are part of the Japanese Society for Spine Surgery and Related Research monitoring working group and the study group on spinal ligament ossification. The authors prospectively analyzed TcMEP variability and pre- and postoperative motor deficits. A 70% decrease in amplitude was designated as the alarm point. RESULTS: There were only 2 false-negative cases, which occurred during surgery for intramedullary spinal cord tumors. This new alarm criterion provided high sensitivity (95%) and specificity (91%) for intraoperative spinal cord monitoring and favorable accuracy, except in cases of intramedullary spinal cord tumor. CONCLUSIONS: This study is the first prospective multicenter study to investigate the alarm point of TcMEPs. The authors recommend the designation of an alarm point of a 70% decrease in amplitude for routine spinal cord monitoring, particularly during surgery for spinal deformity, OPLL, and extramedullary spinal cord tumor. PMID- 24236670 TI - New monoterpene glycosides from the root cortex of Paeonia suffruticosa and their potential anti-inflammatory activity. AB - The methanol extract of the root cortex of Paeonia suffruticosa afforded two new monoterpene glycosides, paeoniside A (1) and paeoniside B (2), and three known monoterpene glycosides, paeoniflorin (3), benzoylpaeoniflorin (4) and 4-O-methyl paeoniflorin (5). Their structures were elucidated on the basis of spectroscopic means including 1D and 2D NMR experiments. Compounds 1-5 were found to be active against cyclooxygenase-1 and cyclooxygenase-2 enzymes. PMID- 24236671 TI - Should high-flux hemodialysis be replaced by online hemodiafiltration for treating end-stage renal disease patients? PMID- 24236672 TI - Patient preferences in diabetes care: overcoming barriers using new strategies. PMID- 24236673 TI - Atypical antipsychotics for older adults: are they safe and effective as we once thought? PMID- 24236674 TI - Children's electronic health records: has the tipping point arrived? PMID- 24236676 TI - The complexities of comparative effectiveness research on devices: the case of robotic-assisted surgery for prostate cancer. PMID- 24236677 TI - Interview: European collaboration in relative effectiveness assessment: the use of patient registries and development of common guidelines. AB - Wim Goettsch is currently the Project Leader of Work Package 5 of the European Network of Health Technology Assessment (EUnetHTA) Joint Action 2 (2012-2015). EUnetHTA is a network of the health technology assessment organizations in Europe responsible for advising or deciding on the national reimbursement of pharmaceuticals and other health technologies. In this work package, rapid joint assessments of the relative effectiveness of pharmaceuticals are piloted between more than 25 health technology assessment organizations around Europe. These pilots are based on the methodology that was developed in a similar work package in EUnetHTA JA1 (2010-2012), of which Dr Goettsch was also the Project Leader. Until the beginning of 2013, Dr Goettsch was the Deputy Secretary of the Medicinal Products Reimbursement Committee at Dutch Healthcare Insurance Board (CVZ). The Dutch Medicinal Products Reimbursement Committee advises the Dutch Minister of Health on whether new drugs need to be included in the basic insurance package. Before joining CVZ, he worked as a research manager for the PHARMO Institute (Utrecht, The Netherlands) and was responsible for the coordination of numerous pharmacoepidemiological and outcomes studies for international offices of pharmaceutical companies, such as AstraZeneca, Novartis, Pfizer and GlaxoSmithKline. Dr Goettsch has approximately 50 publications in peer reviewed international journals. PMID- 24236678 TI - Cemented versus cementless total hip arthroplasty: is a hybrid the most cost effective? AB - Total hip arthroplasty is an extremely successful operation by almost any measure. As the population in the developed world ages, it is also becoming a very popular operation, with nearly 500,000 replacements predicted in the USA by 2030. As more hip replacements need to be performed, the cost will become more of an issue. The debate between the effectiveness of implant types, cemented or cementless, has been ongoing for years. Although largely decided in the USA, in favor of cementless implants, the discussion in the UK continues. There are many studies arguing in favor of implants using cement and for those not using cement. Ultimately, the best implant is the one that is most comfortable in the hands of the surgeon implanting it. Financial factors must be considered, however, and the more information available, the better to help surgeons decide what is best for their patients. PMID- 24236679 TI - Cost-effectiveness of telehealth in the management of chronic conditions. AB - Telehealth has the potential to improve the management of chronic health conditions but there are still limited data on its effectiveness and cost effectiveness in routine practice. A questionnaire study nested within a pragmatic randomized controlled trial estimated costs and outcomes for management of patients in England who had heart failure, chronic obstructive pulmonary disease, or diabetes. Patients received telehealth support and usual care or usual care only. The study perspective was that of the health system. Incremental cost per quality-adjusted life year of telehealth when added to usual care was L79,000. In this setting, telehealth had a low probability of being a cost effective addition to standard care for patients with the chronic conditions. PMID- 24236680 TI - When is evidence sufficient for decision-making? A framework for understanding the pace of evidence adoption. AB - Translation of medical evidence into practice has not kept pace with the growth of medical technology and knowledge. We present three case studies--statins, drug eluting stents and bone marrow transplantation for breast cancer--to propose a framework for describing five factors that may influence the rate of adoption. The factors are: validity, reliability and maturity of the science available before widespread adoption; communication of the science; economic drivers; patients' and physicians' ability to apply published scientific findings to their specific clinical needs; and incorporation into practice guidelines. PMID- 24236681 TI - Room for improvement in breast cancer clinical trial design: taking advantage of the preoperative setting. AB - Achieving approval of new oncologic drugs in breast cancer (BC) is lengthy and costly. After approval in a randomized Phase III trial in metastatic BC, an agent is then evaluated in stage I-III BC. It can take a decade for drug approval in early-stage BC, given the large sample size and long follow-up to detect improvements in disease-free or overall survival. One way to reduce this time period is conducting preoperative trials. In neoadjuvant BC trials, improvements in pathologic complete response in randomized trials of chemotherapy with and without a new agent can lead to accelerated approval. In exploratory investigational new drug trials, such as Phase 0 trials, new drugs can be evaluated for a limited time prior to traditional dose escalation trials. The US FDA has released guidelines for utilization of preoperative trials. The goal is to administer a new agent to the right subset of BC patients quicker and more effectively. PMID- 24236683 TI - A conceptual model of the multiple stages of communication necessary to support patient-centered care. AB - Patient-centered care requires that both healthcare providers and patients have access to comparative effectiveness research (CER), which provides direct comparisons of the risks and benefits of available clinical options. However, insufficient attention has been paid to developing the comprehensive communication systems necessary to ensure that CER reaches patients and healthcare providers. In this review, we propose a model of the multiple stages of CER communication necessary for patient-centered care and review the existing research and gaps in knowledge relevant to each stage. These stages include: promotion of the underlying concepts and value of CER; translation of CER results; dissemination of CER results; and utilization of the results of CER in shared decision-making between patients and providers. A comprehensive approach to CER communication is necessary to ensure that the growing interest in and availability of CER is able to support a more patient-centered model of healthcare. PMID- 24236682 TI - Use of community-based participatory research in primary care to improve healthcare outcomes and disparities in care. AB - Community-based participatory research (CBPR) has emerged to bridge the gap between research and primary-care practice through community engagement and social action to increase health equity. It is widely acknowledged that access to high-quality primary care services is important to the overall health of a community. Here, CBPR studies in a primary care setting are reviewed to assess the use of CBPR associated with common health problems seen in primary care such as access to care and disparities in chronic disease management across vulnerable populations. CBPR involves building relationships with local communities, determining areas of need and establishing priorities for health concerns. Studies showing improved access to care for a Hispanic population, reduced asthma symptoms and weight loss are highlighted. PMID- 24236684 TI - 90Y radioembolization versus chemoembolization in the treatment of hepatocellular carcinoma: an analysis of comparative effectiveness. AB - Locoregional catheter-based therapies for unresectable hepatocellular carcinoma (HCC) include conventional transarterial chemoembolization (cTACE), drug-eluting bead chemoembolization and yttrium-90 ((90)Y) radioembolization. Although current guidelines recommend cTACE for inoperable HCC, comparative effectiveness of drug eluting bead chemoembolization and (90)Y radioembolization in the management of HCC remains undefined due to the lack of data evaluating safety and effectiveness among these therapies. A comprehensive search of the literature was carried out for studies examining comparative effectiveness of cTACE and (90)Y based on objective tumor response and overall patient survival. Further data on efficacy, safety, toxicity and cost-effectiveness was also examined. The National Cancer Institute Levels of Evidence for Cancer Treatment Studies provided a useful framework for the critical understanding and stratification of current evidence on locoregional therapy for unresectable HCC. Based on current retrospective cohort studies, evidence for similar efficacy and safety between cTACE and (90)Y radioembolization was demonstrated. Further prospective, randomized studies are required to validate these observations and to analyze cost-effectiveness of these interventions in unresectable HCC patients for definitive recommendations to be made. PMID- 24236686 TI - What do providers, payers and patients need from comparative effectiveness research on diagnostics? The case of HER2/Neu testing in breast cancer. AB - AIMS: Comparing effectiveness of diagnostic tests is one of the highest priorities for comparative effectiveness research (CER) set by the Institute of Medicine. Our study aims to identify what information providers, payers and patients need from CER on diagnostics, and what challenges they encounter implementing comparative information on diagnostic alternatives in practice and policy. MATERIALS & METHODS: Using qualitative research methods and the example of two alternative protocols for HER2 testing in breast cancer, we conducted interviews with 45 stakeholders: providers (n = 25) from four academic and eight nonacademic institutions, executives (n = 13) from five major US private payers and representatives (n = 7) from two breast cancer patient advocacies. RESULTS: The need for additional scientific evidence to determine the preferred HER2 protocol was more common for advocates than payers (100 vs 54%; p = 0.0515) and significantly more common for advocates than providers (100 vs 40%; p = 0.0077). The availability of information allowing assessment of the implementation impact from alternative diagnostic protocols on provider institutions may mitigate the need for additional scientific evidence for some providers and payers (24 and 46%, respectively). The cost-effectiveness of alternative protocols from the societal perspective is important to payers and advocates (69 and 71%, respectively) but not to providers (0%; p = 0.0001 and p = 0.0001). The lack of reporting laboratory practices is a more common implementation challenge for payers and advocates (77 and 86%, respectively) than for providers (32%). The absence of any mechanism for patient involvement was recognized as a challenge by payers and advocates (69 and 100%, respectively) but not by providers (0%; p = 0.0001 and p = 0.0001). CONCLUSION: Comparative implementation research is needed to inform the stakeholders considering diagnostic alternatives. Transparency of laboratory practices is an important factor in enabling implementation of CER on diagnostics in practice and policy. The incongruent views of providers versus patient advocates and payers on involving patients in diagnostic decisions is a concerning challenge to utilizing the results of CER. PMID- 24236688 TI - Syndrome-associated soft tissue tumours. AB - Soft tissue neoplasms may be associated with a variety of genetic disorders and malformation syndromes, especially when they arise in children, adolescents and early adulthood. This review summarizes the principal histopathological types of soft tissue tumours which occur in various syndromes, with an emphasis on pathological features, genetic aspects and considerations for the diagnostic pathologist. PMID- 24236685 TI - Using a population-based observational cohort study to address difficult comparative effectiveness research questions: the CEASAR study. AB - BACKGROUND: While randomized controlled trials represent the highest level of evidence we can generate in comparative effectiveness research, there are clinical scenarios where this type of study design is not feasible. The Comparative Effectiveness Analyses of Surgery and Radiation in localized prostate cancer (CEASAR) study is an observational study designed to compare the effectiveness and harms of different treatments for localized prostate cancer, a clinical scenario in which randomized controlled trials have been difficult to execute and, when completed, have been difficult to generalize to the population at large. METHODS: CEASAR employs a population-based, prospective cohort study design, using tumor registries as cohort inception tools. The primary outcome is quality of life after treatment, measured by validated instruments. Risk adjustment is facilitated by capture of traditional and nontraditional confounders before treatment and by propensity score analysis. RESULTS: We have accrued a diverse, representative cohort of 3691 men in the USA with clinically localized prostate cancer. Half of the men invited to participate enrolled, and 86% of patients who enrolled have completed the 6-month survey. CONCLUSION: Challenging comparative effectiveness research questions can be addressed using well-designed observational studies. The CEASAR study provides an opportunity to determine what treatments work best, for which patients, and in whose hands. PMID- 24236689 TI - Cobalt(III) diazabutadiene precursors for metal deposition: nanoparticle and thin film growth. AB - We report the synthesis and characterization of a family of cobalt(III) metal precursors, based around cyclopentadienyl and diazabutadiene ligands. The molecular structure of the complexes cyclopentadienyl-Cobalt(III)(N,N' dicyclohexyl-diazabutadiene) (2c) and cyclopentadienyl-Cobalt(III)(N,N'-dimesityl diazabutadiene) (2d) are described, as determined by single crystal X-ray diffraction analysis. Thermogravimetric analysis of the complexes highlighted the isopropyl derivative CpCo((i)Pr2-dab) (2a) as a possible cobalt metal chemical vapor deposition (CVD) precursor. Atmospheric pressure CVD (AP-CVD) was employed using precursor 2a to synthesize thin films of metallic cobalt on silicon substrates under an atmosphere of hydrogen (H2). Analysis of the thin films deposited at substrate temperatures of 250 degrees C, 275 degrees C, 300 degrees C, 325 degrees C, and 350 degrees C, respectively, by scanning electron microscopy (SEM) and atomic force microscopy (AFM) reveal temperature dependent growth features: films grown at 325 and 350 degrees C are continuous and pinhole free, whereas those films grown at substrate temperatures of 250 degrees C, 275 degrees C, and 300 degrees C consist of crystalline nanoparticles. Powder X-ray diffraction (PXRD) and X-ray photoelectron spectroscopy (XPS) all show the films to be high purity metallic cobalt. Raman spectroscopy has also been used to prove the absence of cobalt silicides at the substrate/thin film interface. PMID- 24236690 TI - Ratios of regulatory T cells/T-helper 17 cells and transforming growth factor beta1/interleukin-17 to be associated with the development of hepatitis B virus associated liver cirrhosis. AB - BACKGROUND AND AIM: The aim of this study is to evaluate the association of the regulatory T cells (Treg)/T-helper (Th) 17 cells and transforming growth factor beta1 (TGF-beta1)/interleukin-17 (IL-17) ratios with the survival and disease progression in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). METHODS: The frequencies of Treg and Th17 cells were analyzed in 28 patients with HBV-LC, 70 patients with chronic hepatitis B (CHB) and 20 normal controls (NC) by flow cytometry. The levels of cytokines related to Treg/Th17 differentiation, including IL-10, TGF-beta1, IL-17, and IL-23, were measured by ELISA. RESULTS: Compared with NC, Treg cells were significantly increased in CHB patients and slightly increased in HBV-LC patients, whereas Th17 cells were markedly increased both in patients with CHB and HBV-LC. HBV-LC patients, especially the nonsurvival ones, manifested a profound decrease in the Treg/Th17 ratio, which was negatively correlated with Child-Pugh and model of end-stage liver disease scores. Serum IL-10, TGF-beta1, IL-17, and IL-23 levels were all significantly higher in HBV-LC patients than in NC. In addition, the TGF-beta1/IL 17 ratio was also markedly increased in patients with HBV-LC, especially in nonsurvival and decompensated liver cirrhosis patients, and positively correlated with total bilirubin, Child-Pugh, and model of end-stage liver disease scores. CONCLUSIONS: The decreased Treg/Th17 ratio and increased TGF-beta1/IL-17 ratio may be associated with the survival and disease progression in HBV-LC patients, and both of the two ratios can be used independently to predict the prognosis and disease progression of HBV-LC patients. PMID- 24236691 TI - Current understanding of the process of tooth formation: transfer from the laboratory to the clinic. AB - Teeth are typical examples of organs in which genes determine the progress of development from initiation to the final shape, size and structure, whereas environmental factors play a minor role. Advances in gene technology over the last three decades have led to powerful novel methods to explore the mechanisms of embryonic development. Today we know a few hundred genes that regulate tooth development, and mutations in dozens of these genes have been shown to cause aberrations in tooth development in mice and/or humans. The functions of an increasing number of genes in tooth development have been discovered using genetically modified mouse models. We are now beginning to understand the 'programme' underlying the process of tooth formation. Key components of the programme are signals mediating communication between cells and complex gene regulatory networks in which the signal pathways are integrated. Understanding the mechanisms of tooth development at the level of genes, cells and molecules will lay the basis for new ways to prevent and treat dental defects and diseases. Over the last decade knowledge about dental stem cells has accumulated rapidly and novel stem cell technologies have been developed. Combining stem cell research with knowledge on the mechanisms of tooth development may open up novel possibilities for clinical tooth regeneration. PMID- 24236694 TI - Abstracts of the 6th Trends in Medical Mycology. October 11-14, 2013. Copenhagen, Denmark. PMID- 24236692 TI - Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity. AB - BACKGROUND: Pollen-induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked. OBJECTIVES: To investigate the severity of pollen-induced AR and its determinants in Italian children referred to allergy specialists and who had never received specific immunotherapy (SIT). METHODS: Children (age 4-18 yr) affected by pollen-induced AR who had never undergone SIT were recruited between May 2009 and June 2011 in 16 pediatric outpatient clinics in 14 Italian cities. Recruited children's parents answered standardized questionnaires on atopic diseases (International Study of Allergy and Asthma in Childhood, Allergic Rhinitis and its Impact on Asthma, Global Initiative for Asthma). The children underwent skin-prick test (SPT) with several airborne allergens and six food allergens. Information on socio-demographic factors, parental history of allergic diseases, education, perinatal events, breastfeeding, nutrition and environmental exposure in early life was collected through an informatics platform shared by the whole network of clinical centers (AllergyCARDTM). RESULTS: Among the 1360 recruited patients (68% males, age 10.5 +/- 3.4 yr), 695 (51%) had moderate-to-severe AR, 533 (39%) asthma, and 325 (23.9%) oral allergy syndrome (OAS). Reported onset of pollen-induced AR was on average at 5.3 +/- 2.8 yr, and its mean duration from onset was 5.2 +/- 3.3 yr. Only 6.2% of the patients were pollen-monosensitized, and 84.9% were sensitized to >=3 pollens. A longer AR duration was significantly associated with moderate to-severe AR symptoms (p 0.004), asthma (p 0.030), and OAS comorbidities (p < 0.001). CONCLUSIONS: This nationwide study may raise awareness of the severity of pollen-induced AR among Italian children who have never received pollen SIT. The strong association between pollen-induced AR duration and several markers of disease severity needs replication in longitudinal studies, while suggesting that countrywide initiatives for earlier diagnosis and intervention should be planned. PMID- 24236695 TI - The evolution of laparoscopy in abdominal surgery: a meta-analysis of the effect on infectious outcomes. AB - BACKGROUND: Laparoscopic surgery has been recommended as an effective strategy because of its advantages in decreasing abdominal surgical site infections (SSIs). The aim of this study was to assess the effect of laparoscopy on superficial and organ/space SSIs compared with open surgery in hollow-viscus procedures over time. STUDY DESIGN: Data on SSIs from randomized-controlled trials (RCTs) evaluating open versus laparoscopic abdominal surgeries were extracted from the Cochrane Database Reviews. Re-analysis of these data was performed to assess infections. Heterogeneity was also explored. A subgroup analysis was performed according to elective/emergency surgery status. RESULTS: Data from 72 RCTs including 8218 patients were collected (4116 patients in the laparoscopic group and 4102 patients in the open group). For superficial SSI, the pooled RD was -4.4% (95% CI: -5.4% to -3.3%), which indicated a lower risk in the laparoscopic group. For organ/space SSI, the pooled RD was 0.5% (95% CI: -0.1% to 1%), which indicated similar rates between the groups. Changes in SSI frequency had occurred over time. CONCLUSION: Laparoscopic surgery significantly decreases the risk of superficial SSI but does not affect the risk of organ/space SSI. Experience with technique improves outcomes. PMID- 24236696 TI - Early musical training is linked to gray matter structure in the ventral premotor cortex and auditory-motor rhythm synchronization performance. AB - Evidence in animals and humans indicates that there are sensitive periods during development, times when experience or stimulation has a greater influence on behavior and brain structure. Sensitive periods are the result of an interaction between maturational processes and experience-dependent plasticity mechanisms. Previous work from our laboratory has shown that adult musicians who begin training before the age of 7 show enhancements in behavior and white matter structure compared with those who begin later. Plastic changes in white matter and gray matter are hypothesized to co-occur; therefore, the current study investigated possible differences in gray matter structure between early-trained (ET; <7) and late-trained (LT; >7) musicians, matched for years of experience. Gray matter structure was assessed using voxel-wise analysis techniques (optimized voxel-based morphometry, traditional voxel-based morphometry, and deformation-based morphometry) and surface-based measures (cortical thickness, surface area and mean curvature). Deformation-based morphometry analyses identified group differences between ET and LT musicians in right ventral premotor cortex (vPMC), which correlated with performance on an auditory motor synchronization task and with age of onset of musical training. In addition, cortical surface area in vPMC was greater for ET musicians. These results are consistent with evidence that premotor cortex shows greatest maturational change between the ages of 6-9 years and that this region is important for integrating auditory and motor information. We propose that the auditory and motor interactions required by musical practice drive plasticity in vPMC and that this plasticity is greatest when maturation is near its peak. PMID- 24236697 TI - Age group and individual differences in attentional orienting dissociate neural mechanisms of encoding and maintenance in visual STM. AB - Selective attention biases the encoding and maintenance of representations in visual STM (VSTM). However, precise attentional mechanisms gating encoding and maintenance in VSTM and across development remain less well understood. We recorded EEG while adults and 10-year-olds used cues to guide attention before encoding or while maintaining items in VSTM. Known neural markers of spatial orienting to incoming percepts, that is, Early Directing Attention Negativity, Anterior Directing Attention Negativity, and Late Directing Attention Positivity, were examined in the context of orienting within VSTM. Adults elicited a set of neural markers that were broadly similar in preparation for encoding and during maintenance. In contrast, in children these processes dissociated. Furthermore, in children, individual differences in the amplitude of neural markers of prospective orienting related to individual differences in VSTM capacity, suggesting that children with high capacity are more efficient at selecting information for encoding into VSTM. Finally, retrospective, but not prospective, orienting in both age groups elicited the well-known marker of visual search (N2pc), indicating the recruitment of additional neural circuits when orienting during maintenance. Developmental and individual differences differentiate seemingly similar processes of orienting to perceptually available representations and to representations held in VSTM. PMID- 24236698 TI - Acoustic noise improves visual perception and modulates occipital oscillatory states. AB - Perception is a multisensory process, and previous work has shown that multisensory interactions occur not only for object-related stimuli but also for simplistic and apparently unrelated inputs to the different senses. We here compare the facilitation of visual perception induced by transient (target synchronized) sounds to the facilitation provided by continuous background noise like sounds. Specifically, we show that continuous acoustic noise improves visual contrast detection by systematically shifting psychometric curves in an amplitude dependent manner. This multisensory benefit was found to be both qualitatively and quantitatively similar to that induced by a transient and target synchronized sound in the same paradigm. Studying the underlying neural mechanisms using electric neuroimaging (EEG), we found that acoustic noise alters occipital alpha (8-12 Hz) power and decreases beta-band (14-20 Hz) coupling of occipital and temporal sites. Task-irrelevant and continuous sounds thereby have an amplitude dependent effect on cortical mechanisms implicated in shaping visual cortical excitability. The same oscillatory mechanisms also mediate visual facilitation by transient sounds, and our results suggest that task-related sounds and task irrelevant background noises could induce perceptually and mechanistically similar enhancement of visual perception. Given the omnipresence of sounds and noises in our environment, such multisensory interactions may affect perception in many everyday scenarios. PMID- 24236700 TI - Dietary therapies for eosinophilic esophagitis. AB - Eosinophilic esophagitis (EoE) represents a prevalent chronic esophageal disorder. Since the condition was first described, its pathophysiology has been known to have an immune-allergic origin, but the high response rate to dietary therapies based on feeding patients exclusively with amino acid-based elemental formulas (with complete elimination of table foods) has clearly established EoE as a particular form of food allergy. Nevertheless, the management of EoE in clinical practice remains widely heterogeneous, with topical steroids being a therapeutic mainstay. However, a growing body of evidence points to dietary therapy as an effective treatment option for both children and adults with EoE, as this approach is capable of achieving a sustained symptomatic and histological response without resorting to drugs. This article reviews the available data on the major types of dietary therapy for EoE, including elemental formula diets, skin allergy testing-directed elimination diets and empirical elimination diets based on common food allergens. PMID- 24236699 TI - Magnetoencephalographic activity related to conscious perception is stable within individuals across years but not between individuals. AB - Studies indicate that conscious perception is related to changes in neural activity within a time window that varies between 130 and 320 msec after stimulus presentation, yet it is not known whether such neural correlates of conscious perception are stable across time. Here, we examined the generalization across time within individuals and across different individuals. We trained classification algorithms to decode conscious perception from neural activity recorded during binocular rivalry using magnetoencephalography (MEG). The classifiers were then used to predict the perception of the same participants during different recording sessions either days or years later as well as between different participants. No drop in decoding accuracy was observed when decoding across years compared with days, whereas a large drop in decoding accuracy was found for between-participant decoding. Furthermore, underlying percept-specific MEG signals remained stable in terms of latency, amplitude, and sources within participants across years, whereas differences were found in all of these domains between individuals. Our findings demonstrate that the neural correlates of conscious perception are stable across years for adults, but differ across individuals. Moreover, the study validates decoding based on MEG data as a method for further studies of correlations between individual differences in perceptual contents and between-participant decoding accuracies. PMID- 24236701 TI - The effects of antipsychotic switching on diabetes in chronic schizophrenia. AB - BACKGROUND: People with severe mental illness have a 20-year life-expectancy shortfall. The majority of antipsychotic medications are associated with obesity and heightened diabetes risk. People with severe mental illness less frequently achieve benchmarked diabetes care, often attributed to poor adherence, lower clinical attendance and documented medical biases in treatment. This case is presented to highlight the profound effect medication change can have on diabetes control. CASE REPORT: A 56-year-old man with a 42-year history of schizophrenia had required clozapine treatment for the preceding 14 years. Type 2 diabetes and obesity occurred within 4 years of clozapine instigation. Glycaemic control had been continuously poor, despite frequent contact with diabetes services and multiple medications, including insulin at a dose exceeding 200 IU daily. Request for consideration of antipsychotic review and close interaction with the psychiatry team was initiated at the diabetes outpatient clinic. A gradual medication switch from clozapine to aripiprazole was associated with a reduction in HbA(1c) from 80 to 50 mmol/mol (9.5 to 6.7%) over 4 months, associated with a weight loss of 10 kg. Over the ensuing 2 years, the improvement in HbA(1c) has endured, with total weight loss of 13 kg and halving of insulin requirements. CONCLUSION: This case illustrates the benefits of engagement between endocrinologists and psychiatrists to achieve the shared goal of improved physical health in severe mental illness. Greater interdisciplinary collaboration will help bridge the life-expectancy gap in severe mental illness and may assist in preventing disabling diabetes complications in this vulnerable patient group. PMID- 24236702 TI - Effects of malondialdehyde modification on the in vitro digestibility of soy protein isolate. AB - Soy protein isolate (SPI) was modified by lipid peroxidation product malondialdehyde (MDA), and the in vitro digestibility of modified SPI was investigated. Results indicated that incubation with increasing MDA concentration resulted in significant carbonyl group generation and loss of free amino groups of SPI. Fluorescence loss of natural tryptophan and formation of Schiff base were observed. Noncovalent interaction between molecules was enhanced and became the main force that led to the solubility reduction of MDA-modified SPI. Differential scanning calorimetry (DSC) indicated that SPI had higher thermal stability and lower total calorimetric enthalpy after MDA pretreatment. Electrophoresis showed that beta-conglycinin was more sensitive to MDA modification. In vitro digestion indicated that MDA could induce non-disulfide covalent polymer of SPI, which could not be digested by pepsin and pancreatin. beta subunits of beta-conglycinin became more resistant to digestion with increasing MDA concentration. Evaluation of the free amino acid profile in the digests indicated that MDA-modified SPI had deteriorating nutritive quality. PMID- 24236703 TI - Welcome to Pharmaceutical Patent Analyst. Foreword. PMID- 24236704 TI - A peek inside the launch issue. PMID- 24236705 TI - Role of patent analysis in corporate R&D. PMID- 24236706 TI - A brief history of generic substitution in the USA. PMID- 24236707 TI - The America Invents Act: summarizing the statute. PMID- 24236708 TI - Patent protection in Europe of pharmaceuticals found to have a further medical indication. PMID- 24236710 TI - 'Raising the bar' of patentability. AB - The EPO has faced the public perception that the barrier to patenting is too low and that patent quality has deteriorated. With this in mind, the EPO has initiated a process of strategic renewal called 'raising the bar' with a view to improving the quality of patents and streamlining the grant procedure. This article discusses the changes to the European Patent Convention rules and how these changes aim to improve the quality of granted European patents. PMID- 24236712 TI - The impact of effective patents on future innovations in nanomedicine. AB - The success of nanomedicine is dependent upon an effective protection of IP rights. Unfortunately, the US nanomedicine patent system is dysfunctional because long R&D procedures as well as the patent pendency are insufficiently taken into account. This could be solved by changing the patent-protection starting point and increasing the capacity of the US PTO. The nanotechnology industry also suffers from overlapping patents. This could be avoided by improving the expertise of the PTO, using a more accurate definition of nanotechnology and devising a generally accepted nomenclature that enhances prior-art searches. To avoid disputes, inference practices and strategic patenting can be used. In the case of a dispute, parties can fall back on re-examination, cross-licensing and patent litigation. Cross-licensing agreements are recommended since they allows parties to access technology, create synergies and exclude third-party competitors. Solving the patent problems in the nanotechnology industry is a necessary step for future success. PMID- 24236713 TI - Review of companies and drug classes in the 2007-2011 antihypertensive patent literature. AB - Hypertension, defined as elevated systolic blood pressure and/or diastolic blood pressure generally greater than 140/90 mmHg, is a significant risk factor for cardiovascular outcomes such as arterial aneurysm, myocardial infarction and stroke, and for nonvascular conditions such as Alzheimer's disease. The prevalence of the disease is rapidly increasing both in the USA and in the rest of the world. Hypertension can be managed to a degree through behavioral changes (e.g., reduction in salt intake and loss of excess body weight). When lifestyle changes fail, pharmacological therapy provides benefits, with combination drug therapy often required for many patients to reach their blood pressure-reduction goals. Approximately one-third of hypertensive patients who seek treatment fail to reach their goals, either because they are resistant to drug therapy or stop treatment due to side-effect issues. A medical need exists for new antihypertensive agents with improved risk-benefit profiles. However, within the past decade, the economics of bringing a new antihypertensive agent to market have become challenging due to the plethora of generic drugs available, the advent of polypharmacology, and the difficulty of identifying agents that are better than the standard of care. Only a few new mechanistic classes of antihypertensive agents have been recently approved, suggesting a lack of innovation within the industry. In this review, we describe the results of a survey of drug companies and drug classes in the 2007-2009 antihypertensive patent literature and comment on the current state of innovation in antihypertensive drug discovery. PMID- 24236714 TI - Antibody-drug conjugates in tumor therapy. AB - Antibody-drug conjugates (ADCs) for tumor therapy contain a cytotoxic drug conjugated to a monoclonal antibody (mAb) across a linker. A homing device, the mAb enables the recognition of tumor cells by binding to tumor-specific antigens. The linker is usually cleaved inside the tumor cell or close to the cell surface according to a well-designed chemical mechanism or upon in vivo degradation of the immunoglobulin moiety. The potent drug load is then released exerting its cytotoxic activity within the target cell or in its close proximity (bystander effect). This concept enables a highly selective approach to minimize side effects for the patient. In August 2011, Seattle Genetics' ADC Adcetris(r) (brentuximab vedotin) was approved by the US FDA. This review gives background information on this interesting new technology and presents the relevant, recent patents in this research area. patents by Seattle Genetics, Immunogen and Biotest are discussed owing to their eminent contribution and relevance to the field. PMID- 24236715 TI - Current trends in the development of histone deacetylase inhibitors: a review of recent patent applications. AB - Histone deacetylases (HDACs) have become an important target for the treatment of cancer and other diseases. Currently, more than ten HDAC inhibitors have entered clinical studies and two of them have already reached the market. The hydroxamic acid derivative SAHA (also known as vorinostat or Zolinza(r)) and the cyclic depsipeptide FK228 (romidepsin or Istodax(r)) have gained approval from the US FDA for the treatment of cutaneous T-cell lymphoma. Nevertheless, there has been a continuous effort aimed at discovering a new generation of clinical candidates with improved pharmaceutical properties. This review provides a summary of the most recent patents published from mid-2009 to mid-2011. PMID- 24236716 TI - Na+/K+-ATPase and cancer. AB - The sodium pump, Na(+)/K(+)-ATPase, could be an important target for the development of anticancer drugs as it serves as a versatile signal transducer, plays a key role in cell adhesion and has abnormal expression and activity that are implicated in the development and progression of different cancers. Several publications have reported differing expression of Na(+)/K(+)-ATPase alpha- and beta-subunits in malignant tissues compared with their normal tissue counterparts, thus offering a powerful diagnostic tool. A growing number of patent applications claim the invention or discovery of Na(+)/K(+)-ATPase inhibitors (e.g., cardiac glycosides) to be used to effectively treat certain cancers that are refractory to conventional chemotherapy or radiotherapy. The aims of this review are to provide an overview of the most significant patents that highlight Na(+)/K(+)-ATPase as a valuable target in anticancer therapy and which report on novel Na(+)/K(+)-ATPase inhibitors and ligands designed as potential anticancer agents. PMID- 24236720 TI - Computational medicinal chemistry for rational drug design: Identification of novel chemical structures with potential anti-tuberculosis activity. AB - Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is a common infectious disease with high mortality and morbidity. The increasing prevalence of drug-resistant strains of TB presents a major public health problem. Due to the lack of effective drugs to treat these drug-resistant strains, the discovery or development of novel anti-TB drugs is important. Computer-aided drug design has become an established strategy for the identification of novel active chemicals through a combination of several drug design tools. In this review, we summarise the current chemotherapy for TB, describe attractive target proteins for the development of antibiotics against TB, and detail several computational drug design strategies that may contribute to the further identification of active chemicals for the treatment of not only TB but also other diseases. PMID- 24236722 TI - Prospects for developing new antibacterials targeting bacterial type IIA topoisomerases. AB - The modulation of DNA topology by DNA gyrase and topoisomerase IV, both of which are type IIA topoisomerases and found in most bacteria, is a function vital to DNA replication, repair and decatenation. Despite the potential for resistance development, DNA gyrase and/or topoisomerase IV have been proven to be and remain highly attractive targets in antibacterial drug discovery due to their potential for dual targeting. The search for new GyrA and/or ParC inhibitors that can overcome the increasing spread of multidrug-resistant bacteria has been successfully focused in the last decades on the modification of the known fluoroquinolone scaffold as primarily guided by ligand-based design via classical structure-activity relationship studies and the optimisation of physicochemical properties. This focus has resulted in several novel fluoroquinolones that have been introduced into clinical practice since 2000, and several of these new compounds are currently in different phases of clinical trials. Due to increasing resistance to fluoroquinolones, a significant part of DNA gyrase research has shifted to the discovery of new GyrB and/or ParE inhibitors, which are commonly identified through fragment-based design as well as virtual screening techniques and structure-based hit optimisation programs. This research often results in lead compounds with potent inhibitory activity and promising antibacterial activity profiles. Nevertheless, it is important to understand how different physicochemical properties (e.g., logD and total polar surface area) and different structural motifs influence the compounds' permeability to ensure the efficient discovery of potent, small-molecule antibacterials particularly against Gram-negative strains. PMID- 24236723 TI - Filling the pipeline - new drugs for an old disease. AB - Tuberculosis is a major global health problem. In the middle of the last century several laboratories identified, developed and synthesized several substances which were active against Mycobacterium tuberculosis, the causative agent of the disease. In the 1980s the standard oral treatment regimen was introduced with isoniazid, rifampicin, pyrazinamide, and ethambutol. In combination with the DOTS strategy it was possible treat TB within 6-8 months. But with the emergence of drug resistant strains, the formerly successful regiment became ineffective for MDR and XDR TB patients. Even more alarming, the rapidly increasing HIV epidemic also increases the number of HIV-related TB. Facing these facts, it became evident that novel strategies and antibiotics were needed to treat the new forms of TB. But over the last 60 years no novel TB drug was developed or even in the drug pipeline. But during the last ten years several novel substances have been developed to combat the deadly disease. For the first time in decades the TB drug pipeline is filled again with several promising compounds and many of them have reached Phase II and Phase III clinical trials. Several laboratories and companies all over the world currently are developing and evaluating these substances. This review presents novel substances, which were for the first time exclusively developed for TB such as bedaquilines, nitroimidazoles and the diamine SQ109. We also summarize the present knowledge about enzymes and biosynthesis pathways which offer potential targets for drug discovery against M. tuberculosis. PMID- 24236724 TI - Next generation biofilm inhibitors for Pseudomonas aeruginosa: Synthesis and rational design approaches. AB - The bacterial biofilms and the emergence of multiple drug resistance have become a major threat for current medical treatment of nosocomial infections. It has been estimated that about 65-80% of microbial infections in the developed countries are associated with biofilms. Given the prominence of biofilms in infectious diseases, increasing efforts toward the development of small molecules that will modulate bacterial biofilm development and maintenance is on the rise. Till date, marine natural products have shown a tremendous potential as pharma leads and also given new skeletons which would be used as biofilm/QS inhibitors. Medically relevant biofilm forming bacteria such as Pseudomonas aeruginosa which is most frequently isolated bacteria in nosocomial infection is believed to be a model organism for biofilm studies. Hence, in this review, we have highlighted the development of small molecules that inhibit and/or disperse bacterial biofilms of P. aeruginosa in particular. Additionally, the rational design approaches as well as synthetic methodologies along with biological studies has been accounted in this article. PMID- 24236725 TI - Docking and PLS studies on a set of thiophenes RNA polymerase inhibitors against Staphylococcus aureus. AB - Staphylococcus aureus lives in commensalism with the majority of the population, being recognized as an important pathogen in patients with chronic liver diseases and can cause a deadly infection. The use of antibiotics as rifampin for the chemotherapy of infections caused by S. aureus has resulted in the selection of mutants with resistance. In an attempt to combat resistant strains new research is continuously conducted, as example searching new biological targets or new inhibitors such as tiophenes derivatives that can inhibit the RNA polymerase enzyme. This work investigated the set of tiophenes, selected from of literature and with RNA polymerase enzyme inhibitory activity of S. aureus. After seeking further information on existing scientific literature, the compounds under study were applied the methodologies of PLS, docking and calculation of Molecular Interaction Fields (MIFs) using Pentacle and VolSurf programmes. In addition, a comparison was made with two tiophenes synthesized in our laboratory and which have been tested against the bacteria. Docking studies showed that active compounds had more interactions with the amino acids on active site when compared with rifampicin. The best model obtained in PLS, considering two LVs (latent variables), after leave-one-outvalidation, exhibited the statistical parameters qcv(2) = 0.68 and r(2) = 0.85. External prediction model presented a rext(2) = 0.67. The obtained model through PLS analyses was able to predict the behavior of compounds synthesized by us. So we extract structural features important for the activity of these compounds. In this paper, first we discussed the topics: S. aureus, tiophenes, RNA polymerase, docking and QSAR methodologies. Then we have selected a series of 56 tiophenes from literature, which have their biological activity tested against the RNA polymerase enzyme of S. aureus. The compounds were subsequently carried out for Partial Least Squares (PLS) Analysis. PMID- 24236726 TI - Structure-and-mechanism-based design and discovery of type II Mycobacterium tuberculosis dehydroquinate dehydratase inhibitors. AB - Mycobacterium tuberculosis is the causative agent of tuberculosis, a lethal infection disease that attacks the lungs. Now it becomes the major global health risk because of very long latent period, the persistent increase of new cases, and the emergence of multidrug-resistant and extensively drug-resistant strains. Therefore, there is an urgent need for the development of new, safe and more efficient tuberculosis drugs. The shikimate pathway has been considered as the attractive drug target due to its essentiality in algae, higher plants, bacteria, and fungi, but absence from mammals. In this review, we focus on the recent development of a wide variety of inhibitors of type II Mycobacterium tuberculosis dehydroquinate dehydratase, the third enzyme of this pathway. The structural and mechanistic features of the enzyme for the design and discovery of the inhibitors have been described. The key factors on the structure, binding, and affinity of the inhibitors have been also highlighted. This may direct the further development of type II Mycobacterium tuberculosis dehydroquinate dehydratase inhibitors as potent tuberculosis drugs. PMID- 24236721 TI - Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review. AB - Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID- 24236727 TI - Designing type II topoisomerase inhibitors: A molecular modeling approach. AB - Nosocomial infections are produced by pathogens with the ability to persist in hospital environments and with the propensity to develop resistance to diverse antimicrobials. In order to tackle resistance, it has been pointed as good strategy to select resilient drug targets that are evolutionally constrained to design drugs less susceptible to develop resistance. Molecular modeling can help to fulfill this goal by providing a rationalization of the observed resistance at the molecular level and, suggesting modifications on existing drugs or in the design of new ones to overcome the problem. The present report focus on type II topoisomerases, a clinical validated target for antibacterials and describe diverse modes of intervention including, inhibition of their ATPase function, stabilization of the cleavage complex or prevention of DNA strand hydrolysis. Moreover, the origin of resistance is also rationalized on the base of ligand target interactions. Finally, efforts are described to circumvent the effect of non-susceptible strains by the design of new drugs based on existing ones, like the case of diones that act through the same mechanism as quinolones or the newly released quinole-carbonitrile derivatives that inhibit type II topoisomerases through a new mechanism. PMID- 24236728 TI - New synthetic antibiotics for the treatment of Enterococcus and Campylobacter infection. AB - Bacterial resistance to antibiotics, particularly to multiple drug resistant antibiotics, is becoming cause for significant concern. The only really viable course of action is to discover new antibiotics with novel mode of actions. This review focuses on antibiotic resistance mechanisms of Enterococcus and Campylobacter, and new antibacterial agents against Enterococcus and Campylobacter through de novo or semi- synthesis in the period from 2003 until mid- 2013. PMID- 24236730 TI - Editorial: Nosocomial infections: an increasing challenge to medicinal chemistry. PMID- 24236729 TI - Structure guided design of biotin protein ligase inhibitors for antibiotic discovery. AB - Biotin protein ligase (BPL) represents a promising target for the discovery of new antibacterial chemotherapeutics. Here we review the central role of BPL for the survival and virulence of clinically important Staphylococcus aureus in support of this claim. X-ray crystallography structures of BPLs in complex with ligands and small molecule inhibitors provide new insights into the mechanism of protein biotinylation, and a template for structure guided approaches to the design of inhibitors for antibacterial discovery. Most BPLs employ an ordered ligand binding mechanism for the synthesis of the reaction intermediate biotinyl 5'-AMP from substrates biotin and ATP. Recent studies reporting chemical analogs of biotin and biotinyl-5'-AMP as BPL inhibitors that represent new classes of anti-S. aureus agents are reviewed. We highlight strategies to selectively inhibit bacterial BPL over the mammalian equivalent using a 1,2,3-triazole isostere to replace the labile phosphoanhydride naturally present in biotinyl-5' AMP. A novel in situ approach to improve the detection of triazole-based inhibitors is also presented that could potentially be widely applied to other protein targets. PMID- 24236731 TI - Nitrogen fixation and respiratory electron transport in the cyanobacterium Cyanothece under different light/dark cycles. AB - Incompatibility of nitrogen fixation and oxygen production compels unicellular diazotrophic cyanobacteria to perform photosynthesis during daytime and restrict nitrogen fixation to nighttime. The marine diazotroph Cyanothece BG 043511 was grown in continuous culture under three light/dark regimes (16L : 8D, 12L : 12D, and 8L : 16D h); we monitored nitrogen fixation and potential photosynthetic efficiency simultaneously online to reveal how their temporal separation is affected by different LD regimes. An increase in nitrogen fixation rate at night coincided with a rise in pulse-amplitude modulated fluorescence, indicating that the enhanced respiratory electron transport to fuel diazotrophy affects the oxidation state of the plastoquinone pool. This may offer an alternative approach to assess instantaneous nitrogen fixation activity. Regardless of photoperiod, the maximum rate of nitrogen fixation was conserved at about 20 h after the onset of the light. Consequently, nitrogen fixation rates peaked at different moments in the dark: relatively early in the 16L : 8D cycle, at midnight in 12L : 12D, and relatively late in 8L : 16D. Under 16L : 8D, nitrogen fixation extended into the light, demonstrating the functional plasticity of nitrogen fixation in Cyanothece. Highest daily amounts of nitrogen fixed were obtained in 12L : 12D, which is consistent with the natural LD cycle of subtropical latitudes in which Cyanothece thrives. PMID- 24236733 TI - Surgery versus surveillance of small renal masses: a call for comparative effectiveness research in the management of kidney tumors. PMID- 24236732 TI - Lipopolysaccharide induces cell volume increase and migration of dendritic cells. AB - Migration of dendritic cells (DCs) plays an important role in T-cell-mediated adaptive immune responses. Lipopolysaccharide (LPS) sensed by Toll-like receptor 4 (TLR4) serves as a signal for DC migration. We analyzed LPS-induced DC volume changes preceding the directed movement towards chemoattractants. Treatment with LPS resulted in rapid, prolonged cell swelling in wild-type (WT), but not in TLR4(-/-) bone marrow-derived (BM) DCs indicating that TLR4 signaling is essential for LPS-induced swelling. As a consequence, LPS-treatment enhanced the migratory activity along a chemokine (CCL21)-gradient in WT, but not in TLR4 deficient BMDCs suggesting that the LPS/TLR4-induced swelling response facilitates DC migration. Moreover, the role of calcium-activated potassium channels (K(Ca) 3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS-challenged BMDCs. We found that the LPS-induced swelling of K(Ca) 3.1-deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS-induced increase in [Ca(2+)](i) detected in WT DCs was reduced in K(Ca) 3.1-deficient DCs. Finally, directed migration of LPS-challenged K(Ca) 3.1-deficient DCs was low compared to WT DCs indicating that activation of K(Ca) 3.1 is involved in LPS-induced DC migration. These findings suggest that both TLR4 and K(Ca) 3.1 contribute to the migration of LPS-activated DCs as an important feature of the adaptive immune response. PMID- 24236734 TI - Comparing swabs for diagnosing chlamydia and gonorrhea in women: recent findings. PMID- 24236735 TI - An old tool may fix a new problem: early utilization of 24-h esophageal pH monitoring may reduce unnecessary proton-pump inhibitor use and improve outcomes. PMID- 24236736 TI - Using observational studies for comparative effectiveness: finding quality with GRACE. PMID- 24236738 TI - From methods to policy: Enthusiasm for rapid-learning health systems exceeds the current standards for conducting it. PMID- 24236739 TI - Interview: A private sector life in comparative effectiveness research. Interview with Robert W Dubois. AB - Robert W Dubois joined the National Pharmaceutical Council (Washington, DC, USA) in October 2010 as its Chief Science Officer. In this role, he oversees the National Pharmaceutical Council's research on policy issues related to comparative effectiveness research, as well as on how health outcomes are valued. Dr Dubois has cofounded and led various healthcare research organizations in developing quality research with practical application. Throughout his career, Dr Dubois' primary interest has centered on defining 'what works' in healthcare and finding ways for that evidence to inform healthcare decision-making. He is a recognized expert in the areas of defining best practice, disease management and appropriateness of care. He has authored more than 100 peer-reviewed articles on comparative effectiveness, evidence-based medicine, the development of practice guidelines and determining the optimal use of high-cost medical services. Dr Dubois received his AB from Harvard College (MA, USA), his MD from the Johns Hopkins School of Medicine (MD, USA) and his PhD in Health Policy from the RAND Graduate School (CA, USA). In addition, he is the associate editor of the Journal of Comparative Effectiveness Research and is on the editorial board for Health Affairs. PMID- 24236740 TI - Low-dose computed tomography screening for lung cancer: results of the first screening round. AB - Evaluation of: National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368, 1980-1991 (2013). In 2011, the US NLST trial demonstrated that mortality from lung cancer can be reduced by using low-dose computed tomography (LDCT) screening rather than chest x-ray (CXR) screening. This paper from the US NLST research team focuses on the results of the initial round of LDCT for lung cancer. A total of 53,439 participants were included and randomly assigned to LDCT screening (n = 26,715) or CXR screening (n = 26,724). In total, 27.3% of the participants in the LDCT group and 9.2% in the CXR group had a positive screening result. As a result, 3.8% (LDCT group) and 5.7% (CXR group) of these subjects were diagnosed with lung cancer. The sensitivity (93.8%) and specificity (73.4%) for lung cancer were higher for LDCT compared with CXR screening; 73.5 and 91.3%, respectively. PMID- 24236741 TI - Comparative effectiveness of intravenous and inhaled magnesium in acute asthma. AB - Evaluation of: Goodacre S, Cohen J, Bradburn M et al. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomized controlled trial. Lancet Respir. Med. 1, 293-300 (2013). Acute exacerbations of asthma are common. The current recommended treatment approach to managing an acute asthma exacerbation is to administer a short-acting inhaled beta2-agonist (SABA). SABAs are rapidly effective but may not provide the bronchodilation needed to restore adequate lung function. Consequently, in severe acute asthma exacerbations, despite a standard approach to treatment including SABAs, hospitalization is common. Magnesium is a bronchodilator that may provide additional benefit to SABAs in managing acute asthma exacerbations. In this article, the comparative effectiveness of inhaled and intravenous magnesium in addition to standard therapy is evaluated in the management of severe acute asthma exacerbations. Although neither inhaled nor intravenous magnesium achieved the protocol-specified benefits, intravenous magnesium was associated with fewer hospitalizations and a trend for greater improvement in the symptom of breathlessness than inhaled magnesium. PMID- 24236742 TI - Compassion as the foundation of patient-centered care: the importance of compassion in action. AB - The Institute of Medicine defines patient-centered care as "providing care that is respectful of, and responsive to, individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions." What is missing in this definition is an explicit emphasis on compassion. This perspective article draws on the experience of Planetree (CT, USA), a not-for profit organization that partners with healthcare establishments to drive adoption of patient-centered care principles and practices by connecting healthcare professionals with the voices and perspectives of the patients and family members who utilize their services. Across hundreds of focus groups facilitated by Planetree, patients and their loved ones emphasize that paramount among their needs, preferences and values are compassionate human interactions. For care to be truly patient-centered, a foundation of compassion is essential. Reports from patients and the media, and research from healthcare systems around the world demonstrate the fallacy of assuming that compassion is a current or prevalent feature of the care experience. Concurrently, a growing evidence base highlights the supreme importance of compassion in driving high-quality, high value care. However, good intentions are not sufficient for delivering compassionate care. Drawing on the experiences of exemplary patient-centered hospitals (recognized as such following a rigorous culture audit to determine fulfillment of the criteria for formal recognition as a Designated(r) Patient Centered Hospital [Planetree]), this paper explores practical approaches for embedding compassion in healthcare delivery and organizational culture to meet patients' expressed desires for empathic and respectful human interactions. PMID- 24236743 TI - Engaging older adults in their transitional care: what more needs to be done? AB - Multiple studies reveal that the healthcare needs of chronically ill older adults are poorly managed and often have devastating consequences. This paper examines available evidence related to improving care management and outcomes in this vulnerable patient group. Findings reinforce the need for enhanced patient engagement and suggest comparative effectiveness research as an important and immediate path to optimize patient-clinician partnerships. An ongoing study in care management is described as an example of such comparative effectiveness research. An overview of the barriers to implementation of evidence-based strategies related to health literacy, shared decision-making and accountability for self-management is provided, followed by a set of recommendations designed to facilitate comparative effectiveness research that advances engagement of high risk older adults and their family caregivers. PMID- 24236744 TI - New challenges for comparative effectiveness in oncology: choice of primary end points for randomized clinical trials. AB - Recent advances have led to a steady improvement in cancer treatments. The increasing number of therapeutic options and the corresponding improvement in outcomes pose a number of challenges for comparative effectiveness research in oncology. This review is focused on the choice of primary end points and their interpretation in randomized clinical trials that are designed to inform patients and clinicians on the relative benefits of cancer therapies. We discuss end points that directly measure clinical benefit as well as end points that are thought to be surrogates for clinical benefit. Particular attention is given to the issues associated with the use of overall survival as the primary end point in randomized clinical trials. PMID- 24236745 TI - Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging. AB - AIM: With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. MATERIALS & METHODS: Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. RESULTS: We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. CONCLUSION: Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs. PMID- 24236746 TI - Using modeling to inform patient-centered care choices at the end of life. AB - AIM: Advance directives are often under-informed due to a lack of disease specific prognostic information. Without well-informed advance directives patients may receive default care that is incongruent with their preferences. We aimed to further inform advance care planning in patients with severe chronic obstructive pulmonary disease by estimating outcomes with alternative advance directives. METHODS: We designed a Markov microsimulation model estimating outcomes for patients choosing between the Full Code advance directive (permitting invasive mechanical ventilation), and the Do Not Intubate directive (only permitting noninvasive ventilation). RESULTS: Our model estimates Full Code patients have marginally increased one-year survival after admission for severe respiratory failure, but are more likely to be residing in a nursing home and have frequent rehospitalizations for respiratory failure. CONCLUSION: Patients with severe chronic obstructive pulmonary disease may consider these potential tradeoffs between survival, rehospitalizations and institutionalization when making informed advance care plans and end-of-life decisions. We highlight outcomes research needs for variables most influential to the model's outcomes, including the risk of complications of invasive mechanical ventilation and failing noninvasive mechanical ventilation. PMID- 24236747 TI - Flow cytometric identification of 76 patients with biclonal disease among 5523 patients with chronic lymphocytic leukaemia (B-CLL) and its genetic characterization. AB - Multiparameter flow cytometry (MFC) identifies rare cases of biclonal disease in chronic lymphocytic leukaemia (CLL). By MFC, we identified 76 patients with biclonal disease in a cohort of 5523 CLL patients (1.4%). Fluorescence in situ hybridization and chromosome banding analysis revealed five and six cases, respectively, with two different cytogenetic aberrations due to clonal evolution. Two different B-cell receptor rearrangements and IGHV subtypes were more frequent in biclonal than in monoclonal CLL by MFC (37.1% vs. 2.7%; P < 0.001). Patients with biclonal CLL by MFC showed a trend to a shorter time to treatment than monoclonal CLL (P = 0.080). PMID- 24236748 TI - Thermosensitive AB4 four-armed star PNIPAM-b-HTPB multiblock copolymer micelles for camptothecin drug release. AB - Thermo-sensitive poly(N-isoproplacrylamide)m-block-hydroxyl-terminated polybutadiene-block-poly(N-isoproplacrylamide)m (PNIPAMm-b-HTPB-b-PNIPAMm, m = 1 or 2) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with HTPB as central blocks, and characterization was performed by (1)H NMR, Fourier transform infrared, and size exclusion chromatography. The multiblock copolymers could spontaneously assemble into more regular spherical core-shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension, nanoparticle analyzer, transmission electron microscope (TEM), dynamic light scattering, and UV-vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm, and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature of about 33-35 degrees C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks, and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles. PMID- 24236749 TI - Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease. AB - RATIONALE: The 2007 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend that patients with pulmonary nontuberculous mycobacterial (PNTM) disease caused by Mycobacterium avium complex (MAC) or M. abscessus be treated with a macrolide-based multidrug antibiotic regimen until sputum culture negative for 1 year. After 6 years, the degree of adherence to recommended guidelines among physicians remains unknown. OBJECTIVE: To describe antibiotic treatment practices among physicians treating patients with PNTM in the United States. METHODS: A nationally representative sample of 1,286 U.S. physicians was contacted in December 2011 through January 2012; 582 of the responding physicians were treating patients with PNTM and were eligible to participate. Physicians were asked to extract medical record data on the last four patients they treated in the past year with PNTM disease from either MAC or M. abscessus. Treatment patterns were assessed for all patients by NTM species and physician specialty, and compared with the 2007 recommended ATS/IDSA guidelines. MAIN RESULTS: Questionnaires were completed by 349 physicians on 915 patients with PNTM, including 744 (81%) with MAC and 174 (19%) with M. abscessus; 3 patients were positive for both. Physicians treated 76 (44%) patients with M. abscessus and 411 (55%) patients with MAC. Only 13% of antibiotic regimens prescribed to patients with MAC met ATS/IDSA guidelines, 56% did not include a macrolide, and 16% were for macrolide monotherapy. Among patients with M. abscessus, 64% of regimens prescribed did not include a macrolide. CONCLUSIONS: Adherence to the 2007 ATS/IDSA guidelines for treating PNTM disease is poor. Across all physician specialties evaluated, suboptimal or potentially harmful antibiotic regimens were commonly prescribed. PMID- 24236750 TI - Aspirin resistance in patients with type II diabetes mellitus. AB - BACKGROUND: Diabetic patients exhibit platelet hyperreactivity, which renders them resistant to antithrombotic treatments. We aimed to investigate the prevalence and predictors of aspirin resistance in diabetic patients. MATERIAL AND METHODS: A total of 93 diabetic and 37 non-diabetic participants were included into the study. Aspirin resistance was measured with a whole-blood desktop platelet function analyzer (PFA-100) with an epinephrine agonist. RESULTS: Altogether 41.9% patients with DM were aspirin non-responders. Aspirin resistance was observed in 43.2% of non-diabetic patients (p = 0.89). Presence of diabetes mellitus had no effect on aspirin response (RR 0.95 (95% CI 0.44-2.05), p = 0.89) in the whole study population. Hypercholesterolemia was the only predictor of aspirin resistance in multivariate analysis in diabetic patients (RR 3.09 (95% CI 1.17-8.16), p = 0.023). CONCLUSION: The prevalence of aspirin resistance is comparable in diabetic and non-diabetic patients. Hypercholesterolemia is the only independent predictor of aspirin resistance in diabetic patients. PMID- 24236751 TI - Determinants of endothelial dysfunction in patients with non-alcoholic steatohepatitis. PMID- 24236752 TI - Commentary: acetaldehyde and epithelial-to-mesenchymal transition in colon. AB - Elamin and colleagues in this issue report that acetaldehyde activates Snail, a transcription factor involved in epithelial-to-mesenchymal transition, in an intestinal epithelium. Snail mediates acetaldehyde-induced tight junction disruption and increase in paracellular permeability. Results of this study and other previous studies raise several important questions. This commentary addresses these questions by discussing the acetaldehyde concentration in colon, disruption of epical junctional complexes in the intestinal epithelium by acetaldehyde, and the consequence of long-term exposure to acetaldehyde on colonic epithelial regeneration, carcinogenesis, and metastases. The precise role of acetaldehyde in colonic epithelial modifications and promotion of colorectal cancers still remains to be understood. PMID- 24236753 TI - Temporal regularity facilitates higher-order sensory predictions in fast auditory sequences. AB - Does temporal regularity facilitate prediction in audition? To test this, we recorded human event-related potentials to frequent standard tones and infrequent pitch deviant tones, pre-attentively delivered within isochronous and anisochronous (20% onset jitter) rapid sequences. Deviant tones were repeated, either with high or low probability. Standard tone repetition sets a first-order prediction, which is violated by deviant tone onset, leading to a first-order prediction error response (Mismatch Negativity). The response to highly probable deviant repetitions is, however, attenuated relative to less probable repetitions, reflecting the formation of higher-order sensory predictions. Results show that temporal regularity is required for higher-order predictions, but does not modulate first-order prediction error responses. Inverse solution analyses (Variable Resolution Electrical Tomography; VARETA) localized the error response attenuation to posterior regions of the left superior temporal gyrus. In a control experiment with a slower stimulus rate, we found no evidence for higher order predictions, and again no effect of temporal information on first-order prediction error. We conclude that: (i) temporal regularity facilitates the establishing of higher-order sensory predictions, i.e. 'knowing what next', in fast auditory sequences; (ii) first-order prediction error relies predominantly on stimulus feature mismatch, reflecting the adaptive fit of fast deviance detection processes. PMID- 24236754 TI - Post-injection sciatic neuropathy in a cynomolgus macaque (Macaca fascicularis). AB - BACKGROUND: Intramuscular injection is a common route parenteral used in primates. METHODS: A cynomolgus macaque was evaluated for acute lameness and atrophy of the left leg with no evidence of trauma. RESULTS: History revealed ketamine injection 12 days prior. CONCLUSIONS: Histologic examination supported traumatic injection neuropathy due to intramuscular injection. PMID- 24236755 TI - Recent insights into the pathogenesis of hepatic encephalopathy and treatments. AB - Hepatic encephalopathy (HE) encompasses a spectrum of neuropsychiatric disorders related to liver failure. The development of HE can have a profound impact on mortality as well as quality of life for patients and carers. Ammonia is central in the disease process contributing to alteration in neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling in acute liver failure. Inflammation in the presence of ammonia coactively worsens HE. Inflammation can result from hyperammonemic responses, endotoxemia, innate immune dysfunction or concurrent infection. This review summarizes the current processes implicated in the pathogenesis of HE, as well as current and potential treatments. Treatments currently focus on reducing inflammation and/or blood ammonia levels and provide varying degrees of success. Optimization of current treatments and initial testing of novel therapies will provide the basis of improvement of care in the near future. PMID- 24236756 TI - Editorial for the virtual issue on synthetic inorganic chemistry. PMID- 24236757 TI - Iridium-based lab-on-a-molecule for Hg2+ and ClO- with two distinct light-up emissions. AB - The nonemissive iridium complex 2 is a lab-on-a-molecule for the highly selective detection of Hg(2+) and ClO(-) among 33 analytes using its oxime residues as reactive units. At pH 5, chemodosimeter 2 responds to Hg(2+) by dehydration, whereas at pH 8, it is oxidized by ClO(-), resulting in 450- and 235-fold emission increases, respectively, at two distinct wavelengths. PMID- 24236758 TI - Dividing the spoils: role of pyrazine ligands and perchlorate counterions in the magnetic properties of bis(pyrazine)diperchloratecopper(II), [Cu(pz)2](ClO4)2. AB - A complete first-principles bottom-up computational study of the magnetic properties of [Cu(pz)2](ClO4)2 is presented. A remarkable agreement is observed in the whole range of temperatures between simulated and experimental magnetic susceptibility data. Interestingly, the simulated heat capacity values show an anomaly close to the Neel temperature of 4.21 K associated with a transition from a two-dimensional (2D) antiferromagnet to a three-dimensional (3D) ordered state. The antiferromagnetic behavior of [Cu(pz)2](ClO4)2 is due to a 2D magnetic topology owing to two antiferromagnetic J(AB) interactions through pyrazine ligands. Although presenting a very similar molecular arrangement, the numerical values of the two magnetically significant J(AB) couplings differ by 25% (-10.2 vs -7.3 cm(-1)). This difference can be ascribed to three main contributions: (i) the central pyrazine ring shearing-like distortion, (ii) the effect of the orientation of the perchlorate counterions, and (iii) a hitherto unrecognized skeleton-counterion cooperation arising from different hydrogen bonding contributions in the two most significant J(AB) couplings. The impact of the orientation of the perchlorate counterions is disclosed by comparison to J(AB) studies using structurally similar ligands but with different electronegativity (namely, BF4(-), BCl4(-), and BBr4(-)). Pyrazine ligands and perchlorate counterions prove to be noninnocent. PMID- 24236759 TI - Pentanuclear heterometallic {Ni2Ln3} (Ln = Gd, Dy, Tb, Ho) assemblies. Single molecule magnet behavior and multistep relaxation in the dysprosium derivative. AB - The reaction between Ln(III) chloride and NiCl2.4H2O salts in presence of a multidentate sterically unencumbered ligand, (E)-2,2'-(2-hydroxy-3-((2 hydroxyphenylimino)methyl)-5-methylbenzylazanediyl)diethanol (LH4) leads to the synthesis of four isostructural pentanuclear hetereometallic complexes [Ni2Dy3(LH)4]Cl (1), [Ni2Gd3(LH)4]Cl (2), [Ni2Tb3(LH)3(LH2)]Cl2 (3), [Ni2 Ho3 (LH)3 (LH2)]Cl2 (4) with unprecedented topology. Here the two compounds 1 are 2 are monocationic and crystallize in chiral space group, P2(1)2(1)2(1) whereas compounds 3 and 4 are dicationic and crystallize in achiral space group P2(1)/n. The total metal framework, {Ni2Ln3} unit is held by four triply deprotonated ligands [LH](3-) in 1 and 2 whereas in case of 3 and 4 three triply deprotonated [LH](3-) and one doubly deprotonated [LH2](2-) ligands are involved. In these complexes both the lanthanide ions and the nickel(II) ions are doubly bridged and the bridging is composed of oxygen atoms derived from either phenolate or ethoxide groups. The analysis of SQUID measurements reveal a high magnetic ground state and a slow relaxation of the magnetization with two relaxation regimes for 1. For the thermally activated regime we found an effective energy barrier of U(eff) = 85 K. Micro Hall probe loop measurements directly proof the single molecule magnet (SMM) nature of 1 with a blocking temperature of T(B) = 3 K and an open hysteresis for sweep rates faster than 50 mT/s. PMID- 24236760 TI - Cu(I) thiolate reactivity with dioxygen: the formation of Cu(II) sulfinate and Cu(II) sulfonate species via a Cu(II) thiolate intermediate. AB - Cu(I)(Py2NS) (1) is formed by addition of Cu(I) to a solution of the pyridyl thiol ligand N-(2-mercaptopropyl)-N,N-bis(2-pyridylmethyl)amine (Py2NSH). Oxidation of complex 1 by air leads to the formation of Cu(II) sulfinate and Cu(II) sulfonate complexes, providing a model for the oxidative degeneration of copper-sulfur enzymes. Crystal structures were obtained for two Cu(II) sulfinate complexes, [Cu(II)2(Py2NSO2)2](BF4)2.2(CH3)2CO (4a) and [Cu(II)2(Py2NSO2)2(OTf)2] (4b), which were further characterized by UV-vis and EPR spectroscopy and cyclic voltammetry. Furthermore, two Cu(II) sulfonate complexes with the proposed formulas Cu(II)2(Py2NSO3)2(BF4)2 (5a) and Cu(II)2(Py2NSO3)2(OTf)2 (5b) have been isolated and characterized. Monitoring the oxidation of 1 by UV-vis indicates that the oxidation proceeds via a dinuclear Cu(II) MU-thiolate complex (3); as an intermediate an octanuclear mixed-valent Cu(I)4Cu(II)4 cluster with formula [Cu(I)4Cu(II)4(Py2NS)4(MU-OH)2(CH3CN)6](ClO4)6.2CH3CN (2) was isolated and characterized by X-ray single crystal structure determination. PMID- 24236761 TI - Phototherapy with artificial light suppresses dextran sulfate sodium-induced colitis in a mouse model. AB - BACKGROUND AND AIM: Medical treatment for inflammatory bowel disease (IBD) requires chronic administration and causes side effects. Recently, anti inflammatory effects of phototherapy were reported in animal models. The present study evaluated whether phototherapy improves dextran sulfate sodium (DSS) induced colitis in a mouse model of IBD. METHODS: Mice were divided into four equal groups: Control, DSS, DSS + light low (LL), and DSS + light high (LH) groups. Normal fluorescent light intensity in the Control and DSS groups was 200 lux. Artificial light intensities were as follows: DSS + LL group, 1000 lux; DSS + LH group, 2500 lux. After administering phototherapy for 7 days, we evaluated disease activity index (DAI), histological score, colon length/weight, serum 1,25 dihydroxyvitamin D(3) level, and serum and colonic cytokines in the mice. RESULTS: DAI and histological scores were significantly lower in the DSS + LL group than in the DSS group (both, P < 0.05). Colon length and weight were significantly higher in the DSS + LL group than in the DSS group (both, P < 0.05). Serum interleukin (IL)-6, TNF-alpha, and IL-17 in the DSS + LL group were significantly lower, and serum and colonic IL-10 were significantly higher in the DSS + LL group than in the DSS group (all, P < 0.05). Serum 1,25-dihydroxyvitamin D(3) levels in the DSS + LH group were significantly increased compared with those in the DSS + LL and DSS groups. CONCLUSION: Artificial light phototherapy suppressed DSS-induced colitis in mice by suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines. PMID- 24236762 TI - High-mobility group box-1 (HMGB-1) and serum soluble receptor for advanced glycation end products (sRAGE) in children affected by vernal keratoconjunctivitis. AB - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic disease affecting conjunctiva even though the immunopathogenetic mechanisms underlying this inflammation are unclear. The aim of our study is to investigate serum levels of HMGB1 and circulating sRAGE in children affected by VKC before and after treatment with cyclosporine A (CsA) eye drops and in a group of healthy children. METHODS: Twenty-four children affected by VKC aged between 5 and 12 yrs of life were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, 'Sapienza' University of Rome. Twenty-four healthy children without atopy, ocular, and systemic disease, cross-matched for sex and age to patients affected by VKC, represented the controls. All children affected by VKC were treated with CsA 1% eye drops for 4 wks, and blood samples were collected before and 2 wks after the end of treatment while the controls underwent to a single blood sample at the time of enrollment. RESULTS: Serum basal levels of HMGB1 and sRAGE were higher in children with VKC when compared with controls while, in patients affected by VKC, no difference was detected between atopic and non atopic, and between ANA-positive and ANA-negative children. A significant reduction in serum HMGB1 and sRAGE levels was detected after the therapy while CsA serum levels were negative. CONCLUSIONS: Our study gives a support to the definition of VKC as a systemic inflammation in which HMGB1 and its soluble receptors could play a role. PMID- 24236763 TI - Representation, control, or reasoning? Distinct functions for theory of mind within the medial prefrontal cortex. AB - The medial pFC (mPFC) is frequently reported to play a central role in Theory of Mind (ToM). However, the contribution of this large cortical region in ToM is not well understood. Combining a novel behavioral task with fMRI, we sought to demonstrate functional divisions between dorsal and rostral mPFC. All conditions of the task required the representation of mental states (beliefs and desires). The level of demands on cognitive control (high vs. low) and the nature of the demands on reasoning (deductive vs. abductive) were varied orthogonally between conditions. Activation in dorsal mPFC was modulated by the need for control, whereas rostral mPFC was modulated by reasoning demands. These findings fit with previously suggested domain-general functions for different parts of mPFC and suggest that these functions are recruited selectively in the service of ToM. PMID- 24236764 TI - Age-related and genetic modulation of frontal cortex efficiency. AB - The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency. PMID- 24236765 TI - The role of the cerebellum in dynamic changes of the sense of body ownership: a study in patients with cerebellar degeneration. AB - The sense of the body is deeply rooted in humans, and it can be experimentally manipulated by inducing illusions in at least two aspects: a subjective feeling of ownership and a proprioceptive sense of limb position. Previous studies mapped these different aspects onto anatomically distinct neuronal regions, with the ventral premotor cortex processing subjective experience of ownership and the inferior parietal lobule processing proprioceptive calibration. Lines of evidence suggest an involvement also of the cerebellum, but its precise role is not clear yet. To investigate the contribution of the cerebellum in the sense of body ownership, we applied the rubber-hand illusion paradigm in 28 patients affected by neurodegenerative cerebellar ataxia, selectively involving the cerebellum, and in 26 age-matched control participants. The rubber hand illusion is established by synchronous stroking of the participants' real unseen hand and a visible fake hand. Short asynchronous stroking does not bring about the illusion. We tested the subjective experience of the illusion, evaluated through a questionnaire and the proprioceptive drift of the real unseen hand toward the viewed rubber hand. In patients with cerebellar ataxia, we observed reduced sense of the subjective illusory experience specifically after synchronous stroking. In contrast, the proprioceptive drift was enhanced after synchronous and after asynchronous stimulation. These findings support the contention that the mechanisms underlying the presence of the illusion and the proprioceptive drift may be differently affected in different conditions. Impairment of the subjective sense of the illusion in cerebellar patients might hint at an involvement of cerebellar premotor networks, whereas the proprioceptive drift typically associated with synchronous stroking appears to rely on other circuits, likely involving the cerebellum and the parietal regions. PMID- 24236766 TI - Medial prefrontal theta oscillations track the time course of interference during selective memory retrieval. AB - Memory retrieval is often challenged by other irrelevant competing memories that cause interference. This phenomenon is typically studied with the retrieval practice paradigm in which a category cue (e.g., Fruits) is presented together with an item-specific cue (e.g., Or::). Presentation of the category cue usually induces interference by reactivating competing memories (e.g., Banana, Apple, etc.), which is thought to be solved by means of inhibition, leading to retrieval induced forgetting of these competing memories. Previous studies associated interference with an increase in medial prefrontal theta band (4-8 Hz) oscillations, but these studies could not disentangle the interference from the inhibition processes. We here used a retrieval practice procedure in which the category cue was presented before the item-specific cue to disentangle the interference from the inhibition signal. Furthermore, a competitive retrieval condition was contrasted with a noncompetitive condition. At a behavioral level, retrieval-induced forgetting was found in the competitive but not in the noncompetitive condition. At a neural level, presentation of the category cue elicited higher levels of theta power in the competitive condition, when compared with the noncompetitive retrieval condition. Importantly, this difference was localized to the ACC, which has been associated with the detection and mediation of interference. Additionally, theta power decreased upon presentation of the item-specific cue, and this difference was related to later forgetting. Our results therefore disentangle, for the first time, interference and inhibition in episodic memory retrieval and suggest that theta oscillations track the fine grained temporal dynamics of interference during competitive memory retrieval. PMID- 24236767 TI - Monocular advantage for face perception implicates subcortical mechanisms in adult humans. AB - The ability to recognize faces accurately and rapidly is an evolutionarily adaptive process. Most studies examining the neural correlates of face perception in adult humans have focused on a distributed cortical network of face-selective regions. There is, however, robust evidence from phylogenetic and ontogenetic studies that implicates subcortical structures, and recently, some investigations in adult humans indicate subcortical correlates of face perception as well. The questions addressed here are whether low-level subcortical mechanisms for face perception (in the absence of changes in expression) are conserved in human adults, and if so, what is the nature of these subcortical representations. In a series of four experiments, we presented pairs of images to the same or different eyes. Participants' performance demonstrated that subcortical mechanisms, indexed by monocular portions of the visual system, play a functional role in face perception. These mechanisms are sensitive to face-like configurations and afford a coarse representation of a face, comprised of primarily low spatial frequency information, which suffices for matching faces but not for more complex aspects of face perception such as sex differentiation. Importantly, these subcortical mechanisms are not implicated in the perception of other visual stimuli, such as cars or letter strings. These findings suggest a conservation of phylogenetically and ontogenetically lower-order systems in adult human face perception. The involvement of subcortical structures in face recognition provokes a reconsideration of current theories of face perception, which are reliant on cortical level processing, inasmuch as it bolsters the cross-species continuity of the biological system for face recognition. PMID- 24236769 TI - Germinal mosaicism in a sample of families with Duchenne/Becker muscular dystrophy with partial deletions in the DMD gene. AB - Germinal mosaicism should be considered when estimating the recurrence risk in families with Duchenne/Becker muscular dystrophy (D/BMD). Germinal mosaicism, however, has not been assessed in Mexican families with deletions in the DMD gene. To determine the distribution of deletions in the two hot spots and the proportion of de novo and transmitted deletions, we analyzed 153 individuals with D/BMD and a DMD partial deletion and 322 of their maternal female relatives. Predilection for the distal hot spot was observed in 112 families (73%), while gene dosage analysis of female relatives of D/BMD patients identified germinal mosaicism deletions in at least 11.6% of the patients' families, thought to result from de novo mutations. Recurrence risk due to germinal mosaicism justifies carrier detection in maternal female relatives and prenatal diagnosis in mothers of individuals with apparently de novo DMD deletions. PMID- 24236768 TI - Audiovisual speech integration does not rely on the motor system: evidence from articulatory suppression, the McGurk effect, and fMRI. AB - Visual speech influences the perception of heard speech. A classic example of this is the McGurk effect, whereby an auditory /pa/ overlaid onto a visual /ka/ induces the fusion percept of /ta/. Recent behavioral and neuroimaging research has highlighted the importance of both articulatory representations and motor speech regions of the brain, particularly Broca's area, in audiovisual (AV) speech integration. Alternatively, AV speech integration may be accomplished by the sensory system through multisensory integration in the posterior STS. We assessed the claims regarding the involvement of the motor system in AV integration in two experiments: (i) examining the effect of articulatory suppression on the McGurk effect and (ii) determining if motor speech regions show an AV integration profile. The hypothesis regarding experiment (i) is that if the motor system plays a role in McGurk fusion, distracting the motor system through articulatory suppression should result in a reduction of McGurk fusion. The results of experiment (i) showed that articulatory suppression results in no such reduction, suggesting that the motor system is not responsible for the McGurk effect. The hypothesis of experiment (ii) was that if the brain activation to AV speech in motor regions (such as Broca's area) reflects AV integration, the profile of activity should reflect AV integration: AV > AO (auditory only) and AV > VO (visual only). The results of experiment (ii) demonstrate that motor speech regions do not show this integration profile, whereas the posterior STS does. Instead, activity in motor regions is task dependent. The combined results suggest that AV speech integration does not rely on the motor system. PMID- 24236770 TI - Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes. AB - OBJECTIVE: In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. METHODS: We examined intestinal permeability using chromium ((51) Cr) EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. RESULTS: Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). CONCLUSION: This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. PMID- 24236771 TI - Turn-on persistent luminescence probe based on graphitic carbon nitride for imaging detection of biothiols in biological fluids. AB - Herein, we present a novel strategy based on a "turn-on" persistent luminescence imaging chemical system of graphitic carbon nitride for detecting biothiols in biological fluids. Graphitic carbon nitride (g-C3N4) as persistent luminescence probe is fabricated via a new procedure based on pyrolysis of guanidine hydrochloride under ambient atmospheric conditions. The prepared g-C3N4 nanosheets give intensively long-persistent luminescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The original persistent luminescence of g-C3N4 turns off due to the adsorption of silver ion (Ag(+)) onto g-C3N4 materials with an electron transfer process. The presence of biothiols induces the onset of persistent luminescence emission by interrupting the quenching interaction, thereby turning on the imaging probe. The approach exhibits high specificity and high sensitivity to biothiols with low detection limit for cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) with 6.4, 8.1, and 9.6 nM, respectively. It is also successfully applied for imaging detection of biothiols in human urine, plasma, and cell lysates, demonstrating its great value of practical application in biological systems. PMID- 24236772 TI - Computational studies of the electronic absorption spectrum of [(2,2';6',2" terpyridine)-Pt(II)-OH] [7,7,8,8-tetracyanoquinodimethane] complex. AB - The electronic excitation spectrum of the [(2,2';6',2"-terpyridine)-platinum(II) OH] [7,7,8,8-tetracyanoquinodimethane] ([Pt(trpy)OH]TCNQ) complex has been studied at the linear-response approximate coupled-cluster singles and doubles (CC2) level using triple-zeta basis sets augmented with polarization functions (TZVP). The calculated ultraviolet-visible (UV-vis) spectrum of the [Pt(trpy)OH]TCNQ complex is compared with the UV-vis spectrum measured for [Pt(tbtrpy)OH]TCNQ (tbtrpy = 4,4',4"-(t)Bu3-2,2';6',2"-terpyridine) in dichloromethane (CH2Cl2) solution. The UV-vis spectrum is also compared with the calculated UV-vis spectra of [Pt(trpy)OH](+) and of the neutral and negatively charged TCNQ species. In contrast to previous interpretations, the CC2 calculations suggest that the [Pt(trpy)OH]TCNQ complex is dissociated into [Pt(trpy)OH](+) and TCNQ(-) when dissolved in CH2Cl2. The computed electronic excitation energies of [Pt(trpy)OH](+) provide information about the charge transfer excitations between the Pt(II) metal center and the ligands. The UV-vis spectra were also calculated at the linear-response time-dependent density functional theory (TDDFT) level using the B3LYP, BHLYP, and CAM-B3LYP functionals in combination with TZVP quality basis sets. For the TCNQ species, the TDDFT calculations yield slightly smaller excitation energies than obtained at the CC2 level, whereas for [Pt(trpy)OH](+) the CC2 excitation energies are slightly smaller than the TDDFT ones. For the [Pt(trpy)OH]TCNQ complex, the B3LYP calculations yield spurious low-lying excited states rendering the spectral assignment using B3LYP data difficult. The low-energy part of the electronic excitation spectrum for the [Pt(trpy)OH]TCNQ complex calculated at the BHLYP and CAM-B3LYP levels is reminiscent of the CC2 one because the larger amount of Hartree-Fock exchange and the long-range correction of the potential blue shifts the excitation energies. PMID- 24236773 TI - Harmony and BLyS in Europe and the UK. PMID- 24236774 TI - Emerging patents for cancer-targeted nanomedicines. PMID- 24236775 TI - Unitary European Patent. PMID- 24236776 TI - US patent reform 2011: a few things to remember. PMID- 24236778 TI - IP issues facing researchers by Gino D'Oca. AB - Patents are clearly one of the main drivers of innovation in pharmaceutical and medical R&D. It is increasingly important for researchers at the sharp end to be familiar with the ins and outs of the patenting process. In this feature a panel of experts from academia and industry discuss their experiences of analyzing the patent landscape and preparing applications. Interview conducted by Gino D'Oca, Managing Commissioning Editor. PMID- 24236780 TI - PDK1 inhibitors. AB - PDK1 is a key member of the AGC protein kinase family. It plays an important role in a variety of cellular functions, leading to the activation of the PI3K signaling pathway, an event often associated with the onset and progression of several human cancers. Numerous recent observations suggest that PDK1 inhibitors may provide novel opportunities for the development of effective classes of therapeutics. On these premises, recent years have witnessed an increased effort by medicinal chemists to develop novel scaffolds to derive potent and selective PDK1 inhibitors. The intent of this review is to update the reader on the recent patent literature, covering applications published between June 2008 and September 2011 that report on PDK1 inhibitors. PMID- 24236781 TI - Pharmacological therapies for cataract and refractive errors: landscaping niches of ocular drug patenting. AB - We have used a focused and comprehensive ophthalmology patent database to characterize the international patenting landscape dedicated to the pharmacological treatment of cataract, corneal opacities and dystrophies, and complicated refractive errors. A total of 201 disclosures related to cataract or corneal clouding (published between 1982 and 2011), and 99 documents (published between 1991 and 2011) related to refractive or geometry errors were identified. Current applications for the treatment or prevention of primary cataract have ceased to address diabetic cataract specifically through the inhibition of glycation-specific mechanisms. The most innovative approaches for pharmacotherapy of the lens focus on phase separation inhibitors, modulators of the TGF-beta pathway, and matrix metalloproteinase inhibition. Patenting for the prevention of secondary cataracts as a delayed complication of intraocular lens insertion follows similar routes. For keratoconus, progressive myopia and Avellino corneal dystrophy, the focus remains on efficiently stabilizing the corrected shape of the cornea in the course of orthokeratology treatments. We expect future patenting in the fields of our investigation to concentrate more heavily on molecular medicine, in close lockstep with biotechnology and genetic testing. PMID- 24236782 TI - Kinase inhibitors for CNS diseases: an analysis of the recent patent literature. AB - Protein kinases (PKs), as members of an important target class in current pharmaceutical research, have been mostly exploited so far in therapeutic areas such as oncology and inflammation. However, basic research on some PKs as key components of molecular mechanisms underlying neurodegeneration and neuroprotection may translate into new medicines for CNS diseases in the next few years. This review is an account of recent patents dealing with kinase inhibitors primarily designed for CNS indications. CNS-directed patents on kinase modulators published after 2008 were surveyed using SciFinder((r)) and public patent search engines. Some PK targets, such as GSK-3beta, CDK5, ROCK and p38alpha MAPK, continue to attract interest even though a clinical proof-of-concept is yet to be attained in a CNS setting. Less established PKs such as LRRK2, MLK, PAK and DAPK 1 hold promise as valuable targets of the future. PMID- 24236784 TI - Curcumin suppresses doxorubicin-induced epithelial-mesenchymal transition via the inhibition of TGF-beta and PI3K/AKT signaling pathways in triple-negative breast cancer cells. AB - Triple-negative breast cancer (TNBC) is defined by a lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER 2). Therefore, targeted therapy agents may not be used, and therapy is largely limited to chemotherapy. Doxorubicin treatment consequently acquires undesired malignance characteristics [i.e., epithelial-mesenchymal transition (EMT) and multi-drug resistance]. Our results illustrated that doxorubicin triggered EMT and resulted in the acquisition of a mesenchymal phenotype in TNBC cells. Moreover, we found that transforming growth factor-beta (TGF-beta) and PI3K/AKT signaling pathways were acquired for doxorubicin-induced EMT. Interestingly, we found that curcumin suppressed doxorubicin-induced EMT. Curcumin reversed doxorubicin-induced morphological changes, inhibited doxorubicin-induced downregulation of E-cadherin expressions, and inhibited doxorubicin-induced upregulation of vimentin expression. We also found that curcumin inhibited doxorubicin-induced EMT by inhibiting the TGF-beta and PI3K/AKT signaling pathways. Moreover, curcumin enhanced the antiproliferative effects of doxorubicin in TNBC cells. In summary, our results suggest that doxorubicin in combination with curcumin may be a potential therapy for TNBC. PMID- 24236785 TI - With a little help from EphA3 and polysialic acid: ectodomain shedding of NCAM is gaining momentum. PMID- 24236786 TI - Comparative effectiveness of combination osteoanabolic and antiresorptive therapy for osteoporosis: an update. PMID- 24236788 TI - From methods to policy: Misdiagnosis: an emerging priority for comparative effectiveness research. PMID- 24236789 TI - Interview: achieving STEEEP healthcare: a journey supported by comparative effectiveness research. PMID- 24236790 TI - Role of electronic health records in comparative effectiveness research. PMID- 24236791 TI - The SPECTRUM of findings in treatment options for recurrent/metastatic head and neck cancer. AB - Evaluation of: Vermorken JB, Stohlmacher-Williams J, Davidenko I et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label Phase 3 randomised trial. Lancet Oncol. 14(8), 697-710 (2013). In recent decades, significant progress has been achieved in the biological understanding of squamous cell carcinoma of the head and neck (SCCHN) and the role of human papillomavirus (HPV) has become more evident. The EGF receptor (EGFR) signaling pathway represents the main target of the new therapeutic agents currently in development and has proven to be efficacious in locally advanced SCCHN. The role of HPV in recurrent and metastatic disease for predicting response to EGFR monoclonal antibodies is still unknown. Today, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted therapy approved for the treatment of SCCHN in patients with recurrent or metastatic disease, in association with platinum-based chemotherapy. The identification of novel tumor targets has stimulated the search for other anti-EGFR agents with a more favorable side-effect profile, such as aspanitumumab, but the SPECTRUM study failed to meet its primary end point, stipulating the need to test these agents in clinical trials with a more appropriate choice of study end point. Overall survival, considered a gold standard, may be difficult to interpret if treatment only takes place in a small subinterval of overall survival, therefore, progression-free survival should be used as a surrogate end point for regulatory approval. PMID- 24236792 TI - R-CHOP every 21 days for diffuse large B-cell lymphoma: still the standard of care? AB - Evaluation of: Cunningham D, Hawkes EA, Jack A et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a Phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 381(9880), 1817 1826 (2013). Therapy of newly diagnosed diffuse large B-cell lymphoma is largely unchanged for the past 30 years. Investigators have evaluated if modification of the schedule of drug administration may have a positive effect on outcomes. This article focuses on a recent Phase III clinical trial, which compared every 2- versus 3-week administration of chemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma. The trial found that there was no significant difference between the two dosing schedules. We evaluate the data from this and other trials, and give our recommendations for future studies. PMID- 24236793 TI - Comparative effectiveness research in practice: the Drug Effectiveness Review Project experience. AB - AIM: Assess the effect of the Drug Effectiveness Review Project's comparative effectiveness research findings on prescribing behavior independently and in conjunction with a Medicaid preferred drug list. METHOD: We queried prescription drug claims and enrollment information from the 2001-2008 Medicaid Analytic eXtract and Medicaid Statistical Information System for 17 states using a Wilcoxon signed rank test design to evaluate the effects of the Drug Effectiveness Review Project's report release and preferred drug list implementation on ACE inhibitor prescribing behavior at a state level. The primary outcome of interest was the percentage of ACE inhibitor prescriptions that are defined as 'differentiated' based on the content of the Drug Effectiveness Research Program report. RESULTS: The use of differentiated ACE inhibitors increased significantly in states that participated in the Drug Effectiveness Research Program and subsequently implemented a preferred drug list (p < 0.05, one-tailed). However, there was no significant change in utilization in nonparticipating states or in states that participated but did not subsequently implement a preferred drug list. CONCLUSION: Although the publication of comparative effectiveness research findings may not directly influence practice, a preferred drug list can align utilization with clinical evidence. The states that participate in the Drug Effectiveness Review Project and use preferred drug lists have greater utilization of higher quality drugs, making the combination an effective strategy to translate comparative effectiveness research into practice. PMID- 24236795 TI - Bayesian data analysis in observational comparative effectiveness research: rationale and examples. AB - Many comparative effectiveness research and patient-centered outcomes research studies will need to be observational for one or both of two reasons: first, randomized trials are expensive and time-consuming; and second, only observational studies can answer some research questions. It is generally recognized that there is a need to increase the scientific validity and efficiency of observational studies. Bayesian methods for the design and analysis of observational studies are scientifically valid and offer many advantages over frequentist methods, including, importantly, the ability to conduct comparative effectiveness research/patient-centered outcomes research more efficiently. Bayesian data analysis is being introduced into outcomes studies that we are conducting. Our purpose here is to describe our view of some of the advantages of Bayesian methods for observational studies and to illustrate both realized and potential advantages by describing studies we are conducting in which various Bayesian methods have been or could be implemented. PMID- 24236794 TI - Generic atypical antipsychotic drugs in Belgium: their influence and implications. AB - INTRODUCTION: Generic atypical antipsychotic drugs should be a focus of attention given their expenditure. However, there is a recognized need to tailor treatments. There were no specific measures in Belgium to enhance the prescribing of oral risperidone following generics in January 2008. Prescribing restrictions have remained for long-acting risperidone injections throughout. OBJECTIVE: Assess changes in risperidone utilization before and after oral generics were reimbursed, as well as the utilization and expenditure of the various risperidone preparations. METHOD: Principally a retrospective observational study and interrupted time series design. RESULTS: As expected, no increased utilization of oral risperidone after generics. Both originator and generic oral risperidone prescribed, with the originator reducing its price. Generic risperidone was 59% below prepatent loss prices by September 2012. CONCLUSION: Authorities cannot rely on a 'spill over' of learning from other disease areas to affect changes in physician prescribing habits. Specific measures are needed to encourage generic risperidone where appropriate. However, their influence will be limited by the complexity of the disease area. PMID- 24236796 TI - Oncology training programs: are we doing comparative effectiveness research justice? AB - Comparative effectiveness research (CER) is defined as an assessment of all available options for a specific medical condition, with intent to estimate effectiveness in specific subpopulations. Medical professionals must receive training in CER, including its general goals, the 'toolbox' necessary to perform CER and its design. Oncologic training programs are currently not doing justice to CER: a rationale for conducting CER has been proposed, funding from the US government is available, but encouragement from oncologic residencies and fellowships is minimal. Encouragement to train oncologic physicians in CER is limited by a few factors, including inadequate emphasis on evidence weighing, and no explicit mention of factors key to CER in the Accreditation Council for Graduate Medical Education guidelines. As residency program requirements transition to milestone-based curricula and evaluations, explicit recommendations regarding CER and patient-centered outcomes research should be implemented for all programs. Upper level trainees who have reached milestones related to CER will be competitive applicants for research funding. PMID- 24236797 TI - Comparative effectiveness research in localized prostate cancer treatment. AB - Prostate-specific antigen testing has dramatically increased the incidence of localized prostate cancer. Most men with localized cancer attempt curative therapy, usually with surgery or radiation. However, there is uncertainty about whether and how to best treat these cancers. No published controlled trials have directly compared surgery against radiation or either treatment against active surveillance. Given the indolent nature of prostate cancer and the substantial risks of treatment-related harms, the effects of cancer and treatment on quality of life are important patient-centered outcomes. Comparative effectiveness research, using observational cohorts, claims data and simulation models, enables comparisons of treatments that have not been studied in controlled trials and captures real-world outcomes data to better support informed decision-making. PMID- 24236799 TI - The emerging relevance of heterogeneity of treatment effect in clinical care: a study using stage IV prostate cancer as a model. AB - AIM: Heterogeneity of treatment effect (HTE) occurs when patient factors modify a treatment's effect on health outcomes due to interactions between these factors and the treatment. This article reviews evidence regarding HTE in stage IV prostate cancer (S4PC). METHOD: A systematic literature review was conducted in the MEDLINE and PubMed databases. Inclusion criteria required that articles examine the treatment-related impact of HTE factors on survival, adverse events or health-related quality of life in S4PC patients. The quality of evidence was graded good, fair or poor based on Agency for Healthcare Research and Quality guidelines. RESULTS: The search identified 2659 articles, of which 92 met the inclusion/exclusion criteria. HTE in S4PC was studied for biologic factors including age, race, clinical signs/symptoms, measures of S4PC disease severity, genetic factors, laboratory data, prior treatment, concurrent medications and comorbidities. Nonbiologic factors that were studied included social, geographic and dietary factors. Age and race seldom showed any correlation with S4PC outcomes. CONCLUSION: Diverse biologic and nonbiologic factors contribute to HTE in S4PC. This review in S4PC also provides an approach for examining HTE for other medical conditions. Ultimately, such knowledge can help oncologists prescribe more personalized medicine, help patients make more informed treatment choices, and inform policy-making and treatment coverage decisions. PMID- 24236798 TI - Shared decision-making and comparative effectiveness research for patients with chronic conditions: an urgent synergy for better health. AB - Chronic conditions are the most important cause of morbidity, mortality and health expense in the USA. Comparative effectiveness research (CER) seeks to provide evidence supporting the relative value of alternative courses of action. This research often concludes with estimates of the likelihood of desirable and undesirable outcomes associated with each option. Patients with chronic conditions should engage with their clinicians in deciding which of these options best fits their goals and context. In practicing shared decision-making (SDM), clinicians and patients should make use of CER to inform their deliberations. In these ways, SDM and CER are interrelated. SDM translates CER into patient centered practice, while CER provides the backbone evidence about options and outcomes in SDM interventions. In this review, we explore the potential for a SDM CER synergy in improving healthcare for patients with chronic conditions. PMID- 24236801 TI - Quaternized chitosan-coated nanofibrous implants loaded with gossypol prepared by electrospinning and their efficacy against Graffi myeloid tumor. AB - Nanofibrous poly(L-lactide-co-D,L-lactide) (coPLA) or coPLA/poly(ethylene glycol) implants loaded with plant polyphenolic compound gossypol (GOS) with anti-tumor activity were fabricated by electrospinning. Implants containing quaternized chitosan (QCh) were prepared by coating of the obtained fibrous materials with a thin film of cross-linked QCh. The morphology of the implants and chemical composition of the implant surface were studied by means of scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). In vitro cytotoxicity assay showed that GOS-loaded nanofibrous implants, both non-coated and QCh-coated displayed about two-fold higher inhibitory activity against Graffi tumor cells than that of free GOS at the 72nd h of incubation. As evidenced by the performed fluorescence microscopy analyses and SEM observations, the anti tumor activity of the fibrous implants was mainly due to induction of apoptosis. The experiments in which the implants containing both QCh and GOS were placed locally into the tumor site after the tumor extirpation showed an increase in the survival rate and a lower rate of recurrence in the operative field and of metastases in regional lymph nodes. In this case, 40% of hamsters were alive on the 45th day of implantation and they did not show any clinical sign of recurrence in the operative field and metastases in the regional lymph nodes. PMID- 24236802 TI - Cardiac iron overload assessed by T2* magnetic resonance imaging and cardiac function in regularly transfused myelodysplastic syndrome patients. PMID- 24236803 TI - Systematic approach to determination of maximum achievable capture capacity via leaching and carbonation processes for alkaline steelmaking wastes in a rotating packed bed. AB - Accelerated carbonation of basic oxygen furnace slag (BOFS) coupled with cold rolling wastewater (CRW) was performed in a rotating packed bed (RPB) as a promising process for both CO2 fixation and wastewater treatment. The maximum achievable capture capacity (MACC) via leaching and carbonation processes for BOFS in an RPB was systematically determined throughout this study. The leaching behavior of various metal ions from the BOFS into the CRW was investigated by a kinetic model. In addition, quantitative X-ray diffraction (QXRD) using the Rietveld method was carried out to determine the process chemistry of carbonation of BOFS with CRW in an RPB. According to the QXRD results, the major mineral phases reacting with CO2 in BOFS were Ca(OH)2, Ca2(HSiO4)(OH), CaSiO3, and Ca2Fe1.04Al0.986O5. Meanwhile, the carbonation product was identified as calcite according to the observations of SEM, XEDS, and mappings. Furthermore, the MACC of the lab-scale RPB process was determined by balancing the carbonation conversion and energy consumption. In that case, the overall energy consumption, including grinding, pumping, stirring, and rotating processes, was estimated to be 707 kWh/t-CO2. It was thus concluded that CO2 capture by accelerated carbonation of BOFS could be effectively and efficiently performed by coutilizing with CRW in an RPB. PMID- 24236804 TI - Coexistence of inflammatory hepatocellular adenomas with HNF1alpha-inactivated adenomas: is there an association? AB - AIMS: To report the coexistence of inflammatory hepatocellular adenoma (IHCA) and HNF1alpha-inactivated HCA (H-HCA) in cases from a multicentre study. METHODS AND RESULTS: We report nine cases with the coexistence of IHCA and H-HCA; eight occurred in women, and one in a man. The numbers of nodules and the sizes of the largest and smallest HCAs were variable. In one case, the nodules of the two different subtypes were discovered at different times. In all women, HCAs were histologically typical, regardless of their subtype, whereas H-HCA in the man differed histologically from classic H-HCA. CONCLUSIONS: These cases suggest that a predisposition to develop multiple adenomas, hypothetically caused by a 'benign tumorigenic field effect', although common to all HCAs, may result in different genotypes and phenotypes. Although this is rare, it is expected that more cases with the coexistence of different genotypes will emerge, owing to progress in the use of specific immunohistochemical approaches. PMID- 24236805 TI - Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. PMID- 24236806 TI - Family ecological predictors of physical activity parenting in low-income families. AB - Physical activity (PA) parenting, or strategies parents use to promote PA in children, has been associated with increased PA in children of all ages, including preschool-aged children. However, little is known about the circumstances under which parents adopt such behaviors. This study examined family ecological factors associated with PA parenting. Low-income parents (N = 145) of preschool-aged children (aged 2 to 5 years) were recruited from five Head Start centers in upstate New York. Guided by the family ecological model (FEM), parents completed surveys assessing PA parenting and relevant family and community factors. Hierarchical regression analysis identified independent predictors of PA parenting. Parent depressive symptoms, life pressures that interfere with PA and perceived empowerment to access PA resources were associated with PA parenting. Community factors, including neighborhood play safety and social capital, were not independently associated with PA parenting in the multivariate model. Together, family ecological factors accounted for a large proportion of the variance in PA parenting (R (2) = .37). Findings highlight the need to look beyond cognitive predictors of PA parenting in low-income families and to examine the impact of their broader life circumstances including indicators of stress. PMID- 24236807 TI - Evaluation of an intervention to increase self-efficacy for independent exercise in cardiac rehabilitation. AB - Adherence to independent exercise is an essential outcome of cardiac rehabilitation (CR), yet limited theory-based interventions to improve adherence exist. This study tested the effects of an intervention based on Bandura's conceptualization of self-efficacy. The self-efficacy coaching intervention (SCI), a supplement to standard care, was designed to increase self-efficacy for independent exercise and independent exercise behavior in CR. We examined whether the SCI vs. attention control (AC) resulted in improved exercise self-efficacy (ESE), barriers self-efficacy (BARSE), and minutes of independent exercise for CR participants (n = 65). While between-group differences did not reach significance (p > .10) for any of the outcome measures, significant within-group changes were noted in BARSE scores and independent exercise (p < .001) for the SCI group. Change in independent exercise for the AC group was also significant (p =. 006). Further study is needed to explore whether short-term changes translate into maintenance of independent exercise participation after program completion. PMID- 24236809 TI - Change in positive affect during outpatient cardiac rehabilitation predicts vital exhaustion in patients with coronary heart disease. AB - Vital exhaustion is an acknowledged psychosocial risk factor of incident coronary heart disease (CHD) and recurrent CHD events. Little is known about trajectories in vital exhaustion in patients with CHD and the factors predicting this change. We hypothesized that vital exhaustion would decrease during outpatient cardiac rehabilitation and that an increase in positive affect over time would be associated with decreased vital exhaustion at discharge from cardiac rehabilitation. We also explored the role of the patient's sex in this context. Vital exhaustion was reduced during outpatient cardiac rehabilitation, especially in patients who experienced an increase in positive affect over time (p < .001). This relationship was significant in men (p < .001) but not in women (p = .11). PMID- 24236808 TI - Nocturnal blood pressure non-dipping, posttraumatic stress disorder, and sleep quality in women. AB - Women with posttraumatic stress disorder (PTSD) have poor sleep quality and increased risk of cardiovascular disease (CVD). Non-dipping of nocturnal blood pressure may be an explanatory factor for the relationship between sleep and CVD found in previous research. The current study was designed to determine if non dipping nocturnal blood pressure was associated with trauma exposure, PTSD diagnosis, PTSD symptoms, and sleep quality in a sample of women. Participants completed 24 hours of ABPM and self-report questionnaires. Non-dipping was defined as less than 10% reduction in blood pressure during sleep. The frequency of non-dippers did not differ by diagnostic status (d = .15). However, non dippers endorsed more traumatic event categories (d = .53), more PTSD hyperarousal symptoms (d = .53), poorer overall sleep quality (d = .59), more frequent use of sleep medication (d = .62), greater sleep-related daytime dysfunction (d = .58), and longer sleep onset latencies (d = .55) than dippers. Increased attention to nocturnal blood pressure variation may be needed to improve blood pressure control in trauma-exposed women. PMID- 24236810 TI - The effects of a peer modeling intervention on cardiorespiratory fitness parameters and self-efficacy in obese adolescents. AB - Inconsistencies exist in the assessment and interpretation of peak VO2 in the pediatric obese population, as cardiorespiratory fitness assessments are effort dependent and psychological variables prevalent in this population must be addressed. This study examined the effect of a peer modeling intervention on cardiorespiratory fitness performance and task self-efficacy in obese youth completing a maximal treadmill test. Forty-nine obese (BMI >= 95th percentile for age and sex) youth were randomized to an experimental (received an intervention) or to a control group. The outcome variables were mean and variability cardiorespiratory fitness (peak VO2, heart rate, duration, respiratory exchange ratio), rating of perceived exertion, and task self-efficacy scores. Irrespective of whether a mean or variability score was used, receiving the intervention was associated with non-significant trends in fitness parameters and task self efficacy over time, favoring the experimental group. Cardiorespiratory fitness and task self-efficacy were moderately correlated at both time points. To elucidate the aforementioned findings, psychosocial factors affecting obese youth and opportunities to modify the peer modeling intervention should be considered. Addressing these factors has the potential to improve standard of care in a clinical setting regarding pretest patient education. PMID- 24236811 TI - Disease control in patients with asthma is associated with alexithymia but not with depression or anxiety. AB - This observational cohort study investigated the relationship between alexithymia, coping strategies, anxiety, depression, pulmonary function, and disease control in bronchial asthma (BA) patients who attended a tertiary care center between December 2010 and November 2011. Participants (N = 117) were administered self-report scales measuring anxiety, depression, alexithymia, and coping strategies. Pulmonary function expressed as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow rate over the middle 50% of the FVC (FEF25-75) as% predicted and FEV1/FVC as%, fractional exhaled nitric oxide (FeNO) in ppb and the Asthma Control Test (ACT) were recorded. A hierarchical cluster analysis revealed two clusters of patients with different FEV1 values (p < .001) and alexithymia scores (p < .001). The cluster with lower FEV1 and higher alexithymia used more maladaptive coping strategies (p < .05), and had lower ACT scores (p < .05). Alexithymia was significantly associated with the severity of depression and anxiety symptoms (p < .001 for each comparison). In BA patients, alexithymia was associated with worse pulmonary function and disease control and a more frequent use of maladaptive coping strategies. These results support a multidimensional approach to asthmatic patients, including psychoeducational and behavioral interventions aimed at reducing maladaptive coping strategies. PMID- 24236812 TI - Recognition of facially expressed emotions in patients with fibromyalgia syndrome. AB - The study investigated the ability to identify facially expressed emotions in fibromyalgia syndrome (FMS) and its association with clinical parameters. Thirty five FMS patients and 35 healthy controls accomplished a face recognition task. Additionally, pain severity, alexithymia, depression, anxiety, psychiatric co morbidity and medication use were assessed. The patients displayed reduced task performance in terms of more misclassifications of emotional expressions than controls. Pain severity, alexithymia, depression and anxiety were inversely related to recognition performance, with pain severity accounting for the largest portion of test score variance. Psychiatric co-morbidity and medication had no impact on performance. The study documented impaired emotion recognition in FMS, which may contribute to the interpersonal difficulties and reduced social functioning related to this condition. As potential mechanisms mediating the occurrence of the deficits, altered affective processing due to interoceptive impairment as well as interference of central nervous nociceptive activity with cognitive and emotional processing are discussed. PMID- 24236814 TI - Continuous infusion of propofol or intermittent bolus of tiletamine-zolazepam in feline night monkeys (Aotus infulatus). AB - BACKGROUND: Although commonly used, dissociative anesthesia results in unsatisfactory and long recovery periods. The intravenous anesthetic propofol seems to be the most advantageous solution. The objectives of this study were to investigate the required infusion rate of propofol to maintain surgical anesthesia and to compare it to tiletamine-zolazepam in Aotus infulatus. METHODS: Eight healthy feline night monkeys were anesthetized with propofol (PRO) or tiletamine-zolazepam (TZ) during 60 minutes. Cardiopulmonary parameters, arterial blood gases and lactate and quality and times to recovery were determined. RESULTS: Mean infusion rate of propofol was 0.53 +/- 0.10 mg/kg/minute. Cardiopulmonary effects did not show marked differences between groups. Times for hanging, ventral recumbency, and normal ambulation were lower in PRO. Establishment of desirable anesthetic depth was easier, recovery quality was superior, and lactate levels were lower in PRO. CONCLUSIONS: Compared with tiletamine-zolazepam, minor post-anesthetic adverse events should be expected with propofol anesthesia, as well as faster and better anesthetic recovery. PMID- 24236815 TI - Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes. AB - BACKGROUND: The pathophysiology of alcohol use disorders (AUDs) may be influenced by epigenetics processes such as DNA methylation, but the identification of DNA methylation patterns associated with AUDs has largely been limited to a handful of candidate genes. METHODS: Participants were hazardous drinkers from the local community (n = 309). All participants completed a baseline clinical interview in which they reported on their loss of control over drinking. A subsample participated in an ethanol (EtOH) infusion experiment (n = 50). DNA was extracted from saliva samples and assayed on the Illumina Infinium HumanMethylation27 DNA Analysis BeadChip. RESULTS: We identified significant associations between loss of control over drinking and DNA methylation at multiple CpG sites. In follow-up analyses of one of our top results, a CpG site near the ALDH1A2 gene, we found that methylation was negatively associated with rate of intoxication and self reported feelings of intoxication, consistent with the view that DNA methylation at ALDH1A2 may be associated with changes in alcohol metabolism. CONCLUSIONS: While these findings require replication, they provide evidence that DNA methylation at multiple CpG sites is associated with loss of control over drinking. It may be useful to examine DNA methylation patterns using several related phenotypes to establish the biological coherence of results and to help prioritize markers for further study. PMID- 24236816 TI - Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression. AB - Dlx1, a member of the homeobox domain transcriptional factors, is expressed in a subset of interneurons and is involved in their differentiation. To understand the roles of Dlx1 in dendritic and postsynaptic differentiation, we manipulated Dlx1 expression in both excitatory pyramidal neurons and inhibitory interneurons in hippocampal culture. Exogenous expression of Dlx1 in pyramidal neurons, which lack endogenous Dlx1, resulted in reduced complexity of dendritic arborization. This effect was dependent on the DNA-binding motif of Dlx1. Dlx1 overexpression also induced prominent reduction of spine density, but with mild suppression in the formation of postsynaptic densities. To confirm the roles of endogenous Dlx1, we knocked down Dlx1 in interneurons and found enhanced dendritic growth. By manipulating the expression of possible downstream effectors of Dlx1, neuropilin 2 and p21-activated kinase 3, we provided evidence for the involvement of these two signaling molecules in Dlx1-dependent regulation of dendritic differentiation. Our experimental data support the idea that Dlx1 expression in developing interneurons specifically suppresses two important downstream regulators, leading to the characteristic morphology of Dlx1-expressing interneurons with less branched dendrites and few dendritic spines. PMID- 24236818 TI - The role of metastasectomy in renal cell carcinoma. AB - Despite significant advances in the systemic treatment of metastatic renal cell carcinoma, long-term survival remains low. A potential way to improve outcomes in selected cases is the use of metastasectomy, which is part of the multimodal treatment of this disease. Although the evidence supporting this approach is limited, we believe it is a reasonable option for certain patients. This review summarizes the evidence supporting this approach. PMID- 24236819 TI - Improving surgical outcomes in renal cell carcinoma involving the inferior vena cava. AB - Radical nephrectomy with tumor thrombectomy remains the mainstay of treatment in renal cell carcinoma with inferior vena cava extension. Despite the rapid improvements experienced in perioperative care in recent years, this intervention still often results in significant morbidity and mortality. A deeper understanding of salient features of this complex operation provides a valuable insight into the clinical mechanisms underlying the variations observed in surgical outcomes. The 'operation profile' serves not only as a basis for making an adequate prognostic assessment, but also creates a platform from which 'innovative' strategies for improving quality and safety can be made. The present review aims to set a 'profile' for radical nephrectomy and tumor thrombectomy, and to propose a number of strategies that may reduce the complication rates of this intervention. PMID- 24236820 TI - Medical approaches to non-melanoma skin cancer. AB - Medical therapy represents an alternative treatment approach that can be considered for some forms of non-melanoma skin cancer (NMSC). In selected cases, topical treatments are preferable to invasive procedures, especially in the case of multifocal lesions, unclear lesion edges, risk of keloids, surgical risk factors and localization in some areas such as the face and decolletage, as the cosmetic outcomes are generally excellent. In the case of advanced and metastatic NMSC, molecularly targeted therapy represents a reasonably promising alternative to classical cytotoxic chemotherapy. Based on the existing literature and the authors' experience, this paper analyzes and discusses the mechanisms of action, formulations, official and off-label indications, efficacy, side effects and contraindications of medical treatments that are utilized in the treatment of NMSC, including 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, resiquimod, piroxicam, dobesilate, betulinic acid, vismodegib, cetuximab, gefitinib and cytotoxic chemotherapy. PMID- 24236821 TI - Melanoma patient self-detection: a review of efficacy of the skin self examination and patient-directed educational efforts. AB - Early detection of cutaneous melanoma results in reduced morbidity and mortality. Although screening by physicians has been shown effective, the role of skin self examination (SSE) in melanoma secondary prevention is less well studied. Various methods and educational strategies have been implemented to empower patients to perform efficacious SSEs. Patient demographics play an important role in their likelihood to examine their own skin and ability to detect melanoma. Visual aids such as total body photography and dermoscopy, which have improved physician exams, are becoming elements accessible to patients for augmentation of self exam. This review examines the literature of SSE in melanoma detection. PMID- 24236823 TI - The role of Gliadel wafers in the treatment of high-grade gliomas. AB - Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Standard treatment includes surgery, radiation and chemotherapy. Prognosis is dismal with an average survival of approximately 1 year. Gliadel wafers are one treatment option, working as a source for local chemotherapy delivery. Their use is controversial with questionable survival benefit and potential side effects. We reviewed the literature in an effort to clarify their role in the treatment of high-grade gliomas. A systematic PubMed search was performed using the keywords 'Gliadel', 'carmustine' or 'BCNU wafers' in newly diagnosed high-grade glioma patients. Treatment regimen, and median survival were analyzed. Adverse event ratio was calculated by computing the number of adverse events in a study per patient receiving carmustine wafers. Nineteen studies with 795 patients were included in our review. Survival was 8.7-22.6 months with a mean overall survival (OS) of 16.2 months (control survival is approximately 14 months with surgery and adjuvant chemoradiotherapy). Adverse event ratio using Gliadel wafersin control group. Complication rate was 42.7%. Gliadel wafers may marginally increase survival and local control in newly diagnosed GBM patients but are associated with a high complication rate; therefore, we do not recommend using Gliadel wafers in patients with GBM. Further research may be warranted once a safer alternative to Gliadel wafers has been introduced. PMID- 24236822 TI - Tyrosine kinase inhibition: a therapeutic target for the management of chronic phase chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. New tyrosine kinase inhibitors continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard tyrosine kinase inhibitors. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment. PMID- 24236824 TI - Golgi protein 73, not Glypican-3, may be a tumor marker complementary to alpha Fetoprotein for hepatocellular carcinoma diagnosis. AB - BACKGROUND AND AIM: This study aimed to evaluate the effectiveness of serum Golgi protein 73 (GP73) and Glypican-3 (GPC-3) as tumor markers for diagnosis of hepatocellular carcinoma (HCC). METHODS: A total of 257 subjects were enrolled and consisted of 61 healthy controls, 32 hepatitis B virus carriers, 80 cirrhosis patients, and 84 HCC patients. Diagnosis was performed based on established clinical procedure. Serum GP73, GPC-3, and alpha-fetoprotein were measured. Receiving operating characteristic (ROC) curves were plotted to determine the sensitivity and specificity of each serum marker and their combinations. RESULT: Serum GP73 levels were significantly increased in HCC patients. No significant differences were observed between GP73 and alpha-fetoprotein (AFP) as markers for HCC diagnosis. However, GP73 was more sensitive than AFP in the diagnosis of small HCC. A combination of GP73 and AFP tests increased the sensitivity and specificity for HCC diagnosis. The area under the ROC curve (AUC) of combined test was 0.93 compared with 0.88 for GP73 and 0.90 for AFP alone. GPC-3 tests were negative in all 84 HCC patients. The AUC for GPC-3 is 0.43, indicating that serum GPC-3 was not an effective tumor marker for HCC diagnosis. CONCLUSION: Serum GP73 is a potential tumor marker for HCC diagnosis, especially for differential diagnosis of small HCC and cirrhosis. The combination of GP73 and AFP is more sensitive than AFP alone. Serum GPC-3 does not appear to be an effective tumor marker for HCC diagnosis. PMID- 24236826 TI - An 11-year-old girl with up to 19,200 coughs per day: broadening therapeutic strategies. AB - An 11-year-old girl was transferred to the Universidad de Chile Clinical Hospital after 2.5 months of persistent and unresponsive treatment for coughlike spasms. On arrival, the frequency of symptoms was 1 cough every 4 s, which disappeared during sleep. A multidisciplinary examination excluded allergic, viral, respiratory, epileptic, and other more usual causes of similar conditions. Two diagnoses (psychogenic cough and transient vocal tic disorder) and a mixed intervention were proposed leading to resolution in 12 days of treatment. No recurrence of symptoms was observed during several evaluations within 12 months of medical follow-up. An association between the 2 diagnoses is proposed and discussed. PMID- 24236825 TI - Epidemiology of urticaria in infants and young children in Germany--results from the German LISAplus and GINIplus Birth Cohort Studies. AB - BACKGROUND: Although urticaria is considered one of the most frequent skin diseases, reliable epidemiologic data are scarce. OBJECTIVE: To evaluate the incidence and cumulative prevalence of urticaria in infants and children up to age of 10, to characterize the relationship of specific IgE levels (food and inhalative allergens) with urticaria, and to monitor the joint occurrence of urticaria with other diseases, such as eczema, asthma, and hay fever. METHODS: The study population consisted of two prospective birth cohort studies: the LISAplus and GINIplus studies. Information on physician-diagnosed urticaria, asthma, eczema, or hay fever was collected using self-administered questionnaires completed by the parents. Blood samples were drawn, and specific immunoglobulin E measured at 2 (only LISAplus), 6 and 10 yr of age. RESULTS: The incidence of urticaria was approximately 1% per year of age. The cumulative prevalence of urticaria in children up to the age of 10 yr was 14.5% for boys and 16.2% for girls. Cumulative prevalence of urticaria at the age of ten was significantly (p < 0.05) associated with allergic sensitization to peanut, soy, and wheat flour, but not with inhalant allergens. Both a parental history of atopy/urticaria and the children's diagnosis of asthma, eczema, and hay fever were strongly related (p < 0.0001) to the occurrence of urticaria. CONCLUSIONS: Urticaria is a frequent event during childhood, with highest incidence in infants and preschool children. Comorbidity with atopic disease is high. PMID- 24236827 TI - Trabecular meshwork bradykinin receptors: mRNA levels, immunohistochemical visualization, signaling processes pharmacology, and linkage to IOP reduction. AB - PURPOSE: To localize mRNA and protein of bradykinin (BK) receptors, BK precursor polypeptide (kininogen) mRNA, and to study functional biochemical pharmacology of the signal transduction processes mediated by B2-receptors in isolated human trabecular meshwork (h-TM) cells. Intraocular pressure (IOP) lowering effects of 2 kinins were also investigated. METHODS: Previously documented procedures were utilized throughout these studies. RESULTS: Kinninogen mRNA was most abundant in TM, ciliary body (CB), and optic nerve head and appeared elevated in glaucomatous h-TM tissue. High levels of B2-receptor mRNA were found in the sclera, iris, TM, and CB. B2-receptor subtype protein was localized in cells of the monkey and h TM, and the treatment of isolated h-TM cells with transforming growth factor beta2 (5 ng/mL) caused significant (P<0.04) downregulation of B2-receptor mRNA. In isolated primary h-TM cells, BK (EC50=0.8+/-0.2 nM; n=19) and Met-Lys-BK (EC50=6.5+/-1.5 nM) mobilized intracellular Ca(2+) and induced the release of prostaglandins (PGs) that was blocked by 2 B2-receptor antagonists [HOE-140; (S) WIN-64338]. The cyclooxygenase inhibitor, bromfenac, abolished BK-induced PGs production. BK concentration dependently increased cell impedance, and it significantly (P<0.05) decreased h-TM cell volume in vitro. Intravitreal (ivt) administration of BK (50 MUg), but not a B1-agonist (Sar-[D-Phe(9)]-Des-Arg(9) BK; also at 50 MUg), efficaciously lowered IOP (22.9% to 37% from baseline) of Dutch-Belted rabbits that naturally have high IOPs (27-28 mmHg). CONCLUSIONS: BK activates multiple signal transduction pathways in h-TM cells via B2-receptors that also mediate IOP reduction as observed in rabbits following ivt administration of BK. These ocular hypotensive effects of BK may be physiologically important and suggest a novel therapeutic potential of BK-related B2-agonists. PMID- 24236828 TI - Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. AB - AIMS: Phase III DEFEND-2 investigated whether otelixizumab (3.1 mg over 8 days) preserved C-peptide secretion in patients with new-onset Type 1 diabetes, focusing on adolescents (12-17 years). METHODS: One hundred and seventy-nine patients (54 adolescents) were randomized to otelixizumab or placebo. The primary endpoint was change in 2-h mixed-meal-stimulated C-peptide area under the curve at month 12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1. DEFEND-2 terminated early after 12 months' efficacy and safety follow-up. RESULTS: Change from baseline C-peptide was not significantly different [? = -0.09 nmol/l (95% CI -0.17 to 0; P = 0.051)]. No differential C peptide effect was seen for otelixizumab in adolescents and more adverse events were reported. CONCLUSIONS: Efficacy and tolerability of otelixizumab was similar to DEFEND-1. The 3.1-mg dose was non-efficacious in adults and adolescents. Further investigation of the mechanism of action seen at higher doses and therapeutic window is required. Clinical Trials Registry No: NCT 00763451. PMID- 24236829 TI - A contemporary analysis of induction immunosuppression in pediatric lung transplant recipients. AB - There is an increasing trend in the use of induction immunosuppression in children undergoing lung transplantation (LTx). To evaluate the effect of this practice on survival, the United Network for Organ Sharing (UNOS) was queried from 1987 to 2012, restricting analysis to transplant patients 6-17 years old from 2001 to 2012, who received no induction (NONE) or induction (INDUCED) with the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin (ALG), or antithymocyte globulin (ATG). Of 23 951 lung transplants, 330 met inclusion criteria with 177 (54%) being INDUCED. Of the INDUCED agents, 121 (68%) were basiliximab, 3 (2%) alemtuzumab, and 53 (30%) ALG/ATG/thymoglobulin. The mean patient age was 13.6 (SD = 3.2) and 14 (SD = 3.0) years for the INDUCED and NONE groups, respectively. The median survival in the INDUCED group was 77.4 months (95% CI: 46.1, 125.6) compared with 50.8 months (95% CI: 42.9, 61.3) for the NONE (log-rank P-value = 0.3601). The most common cause of death was due to allograft failure or pulmonary complications with only one patient dying from post-transplant lymphoproliferative disorder. The estimated hazard ratio for INDUCED versus NONE was 0.859 (95% CI: 0.620, 1.191; P = 0.3618); there were no significant confounders or effect modifiers among the demographic and clinical variables. In conclusion, antibody-based induction immunosuppression with contemporary agents had a trend toward a protective, but not statistically significant, effect in 6- to 17-year-old patients. PMID- 24236830 TI - Paroxysmal nocturnal haemoglobinuria phenotype cells and leucocyte subset telomere length in childhood acquired aplastic anaemia. AB - The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; 11/16 (69%) achieved complete response (CR). Only 2/6 (33%) PNH(neg) patients achieved PR. PNH(pos) patients were less likely to fail IST compared to PNH(neg) patients (odds ratio 0.033; 95% confidence interval 0.002-0.468; P = 0.012). Children with AA had short granulocyte (P = 7.8 * 10(-9) ), natural killer cell (P = 6.0 * 10(-4) ), naive T lymphocyte (P = 0.002) and B lymphocyte (P = 0.005) telomeres compared to age-matched normative data. PMID- 24236831 TI - Current patenting trends for biologics versus small molecules. PMID- 24236832 TI - Focus, medicinal chemistry, informatics: towards the pharmaceutical patentome. PMID- 24236833 TI - Reaction to the Brustle decision. PMID- 24236834 TI - How high is too high for the threshold on patent utility? PMID- 24236835 TI - Chemistry and the law. AB - The Chemistry and the Law Division of the American Chemical Society met in San Diego in March 2012. The divisional meeting was attended by patent attorneys, patent analysts and scientists who are all united by the business need to effectively deal with patent prosecution, patent research, litigation and licensing. This report highlights some of the presentations from the divisional sessions. PMID- 24236836 TI - The transatlantic divide: how divisional and continuing patent application filing practice differs between the USA and Europe. AB - In this article we compare patent application 'fragmentation' strategies in the USA and Europe. Recent changes in European law restricting the timeframe in which divisional applications may be filed now make adopting a US-style approach in Europe virtually impossible. Life-science originator companies must therefore use foresight to direct the filing of appropriate divisional applications to meet the narrowed window of opportunity in Europe. PMID- 24236837 TI - US patent reform: a European perspective. AB - This article describes a significant change in US patent practice that will see it become more aligned with the patent practice in most if not all of the rest of the world. This change follows recent legislation in the US that has transformed the manner in which the USPTO treats issues as fundamental as the date of an invention, and also opens the way for more economical challenges to the validity of patents after grant. PMID- 24236840 TI - Chemical structure searching: taking it to the next level. AB - Chemical structure searching can be challenging. The most common question in a searcher's mind is, "is my search comprehensive?" What he least wishes to hear from a client is, "why did you miss this?" This article will discuss ways of expanding the scope of structure searches conducted in the pharmaceutical industry. Patent offices commonly search a broad 'core' structure in the context of a drug indication (e.g., thyroid cancer) or a drug's mechanism of action (e.g., PDE5 inhibitors). Other approaches include patent citation searching of relevant references, the use of pharmaceutical pipeline databases and inventor/assignee-based searches. During analysis of the results, it can be useful for an analyst to include such references in the report (e.g., as 'reference of possible interest'), while also indicating which techniques were used to retrieve them. Regardless of whether these additional search techniques provide further relevant references, the search report is still more comprehensive and, therefore, less likely to omit relevant art. PMID- 24236841 TI - Supplementary Protection Certificates for medicinal products: where are we now and what challenges lay ahead? AB - In Europe, Supplementary Protection Certificates have been available for human and veterinary medicinal products since 1993. Although certain fundamental issues surrounding them have been resolved, questions still remain about their scope and whether they can be obtained at all for some products. This article explores where we are now and what challenges lay ahead. PMID- 24236843 TI - Glucokinase activators. AB - In this review we highlight recently disclosed progress in the field of small molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic. PMID- 24236842 TI - GPR119 agonists 2009-2011. AB - The increasing incidence of Type II diabetes mellitus worldwide continues to attract the attention and resources of the pharmaceutical industry in the pursuit of more effective therapies for blood glucose control. New approaches that compare favorably with classical medicaments while avoiding hypoglycemic episodes or waning effectiveness are paramount. Recent advances toward this end have been realized based on the biology of the glucagon like peptide-1 receptor (GLP1R). This beta-cell-expressed GPCR has the ability to promote insulin release in a glucose-dependent fashion, and has been shown to elicit improved glycemic control and preservation of beta-cell mass. Direct activation of GLP1R utilizing peptide mimetics has been achieved; however, attempts to access the biology of this receptor via small-molecule approaches have thus far been elusive. In this context, GPR119 has emerged as a tractable new alternative to GLP1R. GPR119 is another GPCR expressed on the beta-cell, which, like GLP1R, signals in a glucose dependent manner. Moreover, GPR119-mediated increases in GLP-1 and other incretins upon activation in the intestine further increase the insulinotropic activity of the beta-cell. The early success in identifying small-molecule agonists of the GPR119 has prompted a rapid increase in the number of patent applications filed in the last few years. In this review we provide a comprehensive summary of all patent activity in this field that has appeared within the 2009-2011 timeframe. PMID- 24236844 TI - The A to Z of pharmaceutical cocrystals: a decade of fast-moving new science and patents. AB - From aspirin to zoledronic acid, pharmaceutical cocrystals emerged in the past decade as a promising new weapon in the arsenal of drug development. Resurgence of interest in multicomponent crystal compositions has led to significant advances in the science of cocrystal design and discovery. These advances have built upon crystal engineering, which provides a deep understanding of supramolecular interactions between molecules that govern crystal packing and physicochemical properties of crystalline materials. Concomitantly, the patent landscape of pharmaceutical cocrystals developed rapidly in the last decade. This review presents a broad survey of patents issued in the area of pharmaceutical cocrystals. In addition, the review contains analyses of key patents in the area involving compositions and methodologies. Along the way, the main events of the past decade representing a renaissance of cocrystals of pharmaceutical materials are chronicled. Future directions in the area are discussed in light of key pending patent applications and recent publications of seminal interest. PMID- 24236845 TI - Orexin receptor antagonists. AB - The orexin neuropeptides bind to two G protein-coupled receptors, orexin-1 and 2. Small-molecule antagonism of the receptors has potential therapeutic utility in a number of areas, most notably insomnia, for which the most advanced dual orexin receptor antagonist has now completed clinical trials. The purpose of this article is to comprehensively review small-molecule orexin antagonist patent activity during the period 2009-2011. PMID- 24236847 TI - Enhanced cadmium resistance and accumulation in Pseudomonas putida KT2440 expressing the phytochelatin synthase gene of Schizosaccharomyces pombe. AB - Phytochelatins (PCs) are cysteine-rich peptides with high binding affinity for toxic metals. Expressing the PC synthase gene (PCS) in plant growth-promoting bacteria may enhance its metal resistance and accumulation, consequently increasing phytoremediation efficiency in heavy metal pollution. In this study, PCS from Schizosaccharomyces pombe was cloned and expressed in Pseudomonas putida KT2440, which was confirmed by real-time RT-PCR through an increase in SpPCS mRNA expression level when induced by 20 MUmol of CdCl2 in the transformed Ps. putida cells. The recombined strain KT2440-SpPCS exhibited enhanced Cd, Ag and Hg resistance. Compared with the original strain, KT2440-SpPCS also displayed a threefold to fivefold increase in Cd accumulation (14.32 MUmol g(-1) to 17.38 MUmol g(-1) ; dry weight) when grown in 30 and 50 MUmol CdCl2 , along with an increase in nonprotein thiols. Further experiments showed significantly enhanced germination rates and growth of wheat seeds in 0.1 mmol to 1.0 mmol Cd when inoculated with KT2440-SpPCS. This study shows potential use of Ps. putida KT2440 SpPCS in plants to construct a symbiotic system for an enhanced phytoremediation of heavy metal-contaminated environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The symbiotic system of using plant growth-promoting bacteria Pseudomonas putida to express phytochelatin synthase gene of Schizosaccharomyces pombe together in plants resulted in high heavy metal resistance and high accumulation capacity, suggesting potential enhancement in phytoremediation of heavy metal-contaminated environments. PMID- 24236848 TI - Longitudinal associations among fathers' perception of coparenting, partner relationship quality, and paternal stress during early childhood. AB - This study examined the longitudinal and concurrent associations among fathers' perceptions of partner relationship quality (happiness, conflict), coparenting (shared decision making, conflict), and paternal stress. The sample consisted of 6,100 children who lived with both biological parents at 24 and 48 months in the Early Childhood Longitudinal Study-Birth Cohort data set. The results showed that there are significant and concurrent associations between fathers' perceptions of the coparenting relationship and paternal stress, and between partner relationship quality and paternal stress. There was also a positive direct longitudinal association between partner relationship conflict and paternal stress. However, we found only one longitudinal cross-system mediation effect: fathers' perception of coparenting conflict at 48 months mediated the association between partner relationship conflict at 24 months and paternal stress at 48 months. The family practice implications of these findings are discussed. PMID- 24236849 TI - Analysis of quantitative trait loci in mice suggests a role of Enoph1 in stress reactivity. AB - Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression. Next, all animals were genotyped with 269 microsatellite markers with a mean distance of 5.56 cM. Finally, a Quantitative Trait Loci (QTL) analysis was carried out, followed by selection of candidate genes. The QTL analysis revealed several new QTL on chromosome 5 with a common core interval of 19 Mb. We further narrowed this interval by comparative genomics to a region of 15 Mb. A database search and gene prioritization revealed Enoph1 as the most significant candidate gene on the prioritization list for anxiety and also for depression fulfilling our selection criteria. The Enoph1 gene, which is involved in polyamine biosynthesis, is differently expressed in parental strains, which have different brain spermidine levels and show distinct anxiety and depression-related phenotype. Our result suggests a significant role in polyamines in anxiety and depression-related behaviors. PMID- 24236850 TI - CDC's winnable battles: improved nutrition, physical activity, and decreased obesity. PMID- 24236851 TI - Fragmentation of positively-charged biological ions activated with a beam of high energy cations. AB - First results are reported on the fragmentation of multiply protonated polypeptide ions produced in electrospray ionization mass spectrometry (ESI-MS) with a beam of high-energy cations as a source of activation. The ion beam is generated with a microwave plasma gun installed on a benchtop Q Exactive mass spectrometer. Precursor polypeptide ions are activated when trapped inside the collision cell of the instrument (HCD cell), and product species are detected in the Orbitrap analyzer. Upon exposure to the beam of air plasma cations (~100 MUA, 5 s), model precursor species such as multiply protonated angiotensin I and ubiquitin dissociated across a variety of pathways. Those pathways include the cleavages of C-CO, C-N as well as N-Calpha backbone bonds, accordingly manifested as b/y, a, and c/z fragment ion series in tandem mass spectra. The fragmentation pattern observed includes characteristic fragments of collision-induced dissociation (CID) (b/y/a fragments) as well as electron capture/transfer dissociation (ECD, ETD) (c/z fragments), suggesting substantial contribution of both vibrational and electronic excitation in our experiments. Besides backbone cleavages, notable amounts of nondissociated precursor species were observed with reduced net charge, formed via electron or proton transfer between the colliding partners. Peaks corresponding to increased charge states of the precursor ions were also detected, which is the major distinctive feature of ion beam activation. PMID- 24236852 TI - Exploring a Dutch paradox: an ethnographic investigation of gay men's mental health. AB - Despite the Netherlands' reputation as a world leader with respect to gay rights, homosexual Dutch men have much higher rates of mood disorders, anxiety disorders and suicide attempts than heterosexual Dutch men. Epidemiologists report similar disparities elsewhere in Western Europe and North America. These findings have been the focus of a blossoming psychological literature, inspired by minority stress theory and deploying quantitative methods. Our investigation aims to complement this body of work by adopting an ethnographic approach. Drawing from fieldwork conducted in the Netherlands from 2009 to 2010, we explore sociocultural and contextual factors that have received relatively little attention with respect to gay mental health. In the Netherlands - considered a model for gay equality - how can one understand high rates of psychiatric disorders among gay men? This study points to heteronormativity, complex dynamics involving long-term relationships and processes within gay subcultures as key issues. Notwithstanding their putative socioeconomic, legal and political equality, gay men struggled - at various stages of the life cycle - with internalised norms that they found difficult to fulfil. The desire to embody these ideals, and structural constraints in meeting them, could be potent sources of disappointment and distress. PMID- 24236853 TI - Positioning of leukocyte subsets in the portal and lobular compartments of hepatitis C virus-infected liver correlates with local chemokine expression. AB - BACKGROUND AND AIM: Chronic hepatitis C virus infection is characterized by infiltration of a mixed population of leukocytes into portal tracts and infiltration almost exclusively by CD8+ T cells into lobules of the liver. This pattern of leukocyte recruitment is likely to be orchestrated in a cell-specific fashion by local chemokine expression. METHODS: Portal or lobular tissues were isolated by laser capture microdissection from 17 liver biopsy specimens to examine regional gene expression of a panel of chemokine ligands and receptors. The biopsies were also stained immunohistochemically to enumerate regional cell numbers. RESULTS: Expression of multiple chemokine ligands and receptors was evident, although few correlated with leukocyte numbers. In the lobule, expression of CXCL10 correlated with T-cell subsets (CD3+, P = 0.0002; CD4+, P = 0.0053; and CD8+, P = 0.0061), as did CCL5 (CD3+, P = 0.0005; CD8+, P = 0.0199) and CCL3 (CD3+, P = 0.0016; CD8+, P = 0.008). In the portal tracts, expression of CXCL10 and CCL5 was correlated with CD8+ T-cell numbers (P = 0.0040 and P = 0.0114, respectively), whereas CXCL13 was strongly correlated with CD20+ B-cell numbers (P < 0.0001). CXCR3 expression correlated with CD3+ and CD4+ T cells (P < 0.0001 and P = 0.0208, respectively), CCR5 with CD8+ T cells (P < 0.0001), and CXCR5 with CD20+ B-cell infiltration (P = 0.0022). CONCLUSION: CXCR3, CCR5, and CXCR5 and their ligands form key elements of the "zip code" responsible for regional localization of specific lymphocyte subsets in the HCV-infected liver. PMID- 24236854 TI - Contribution of the NS1 gene of H7 avian influenza virus strains to pathogenicity in chickens. AB - Using reverse genetics (rg), we generated two reassortant viruses carrying the NS1 gene of two closely related HPAIV and LPAIV H7N1 variants (designated rgH7N7 HP(HPNS1) and rgH7N7 HP(LPNS1), respectively) in the backbone of the HP H7N7 strain A/Chicken/Netherlands/621557/03 (rgH7N7 HP). Comparison of these reassortants allowed us to determine the effect of amino acid differences in the nuclear export and nucleolar localization sequences of NS1 on pathogenesis in chickens. Compared to rgH7N7 HP(LPNS1), a delay in weight gain and an increase in mortality were observed for rgH7N7 HP(HPNS1). Furthermore, an increase in viral load in brains, lungs, and cloacal swabs, as well as an increased induction of mRNA for type I interferons and pro-inflammatory cytokines in brains, were observed for rgH7N7 HP(HPNS1). Comparison of rgH7N7 HP(LPNS1) with the backbone strain rgH7N7 HP allowed us to examine differences in pathogenesis due to differences in NS1 alleles. rgH7N7 HP, which contained allele A of NS1 showed a higher in vitro replication rate and proved to be more virulent than the isogenic virus carrying allele B of NS1(rgH7N7 HP(LPNS1)). In addition, higher virus accumulation in the lungs and brains, and an increased induction of host gene responses, especially in the brains, were found for rgH7N7 HP compared to rgH7N7 HP(LPNS1). No large differences were observed in type I interferon expression in the lungs of chickens infected with any of the viruses, suggesting that differences in virulence due to differences in NS1 could be related to differences in the induction of pro-inflammatory cytokines in vital organs such as the brains. PMID- 24236857 TI - Nanostructured aqueous lithium-ion conductors formed by the self-assembly of imidazolium-type zwitterions. AB - In the present study, we have synthesized a room-temperature ionic liquid by mixing imidazolium-type zwitterions with lithium bis(trifluoromethanesulfonyl)imide. We constructed nanostructured aqueous lithium ion conductors having hexagonal, lamellar, and bicontinuous cubic structures by the self-assembly of this amphiphilic ionic liquid. These nanostructured lithium ion conductors exhibited an assembled-structure dependent lithium-ion conduction behavior. The introduction of highly ordered and well-defined liquid crystal structures into room-temperature ionic liquid radically changes the conduction mechanism from diffusion to hopping. PMID- 24236855 TI - Mucosal adjuvants for influenza virus-like particle vaccine. AB - To find an effective mucosal adjuvant for influenza virus-like particles (VLPs), we compared the effects of known adjuvants Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, gardiquimod, and cholera toxin (CT). Mice that were intranasally immunized with Alum, CpG, MPL, and CT adjuvanted VLPs showed higher levels of antibodies in both sera and mucosa. Hemagglutination inhibition and virus neutralizing activities were enhanced in groups adjuvanted with Alum, MPL, or CT. Influenza virus specific long-lived cells secreting IgG and IgA antibodies were found at high levels both in bone marrow and spleen in the Alum, CpG and CT adjuvanted groups. A similar level of protection was observed among different adjuvanted groups, except the CT adjuvant that showed a higher efficacy in lowering lung viral loads after challenge. Alum and CT adjuvants differentially increased influenza VLP-mediated activation of dendritic cells and splenocytes in vitro, supporting the in vivo pattern of antibody isotypes and cytokine production. These results suggest that Alum, MPL, or CpG adjuvants, which have been tested clinically, can be developed as an effective mucosal adjuvant for influenza VLP vaccines. PMID- 24236856 TI - Innate immune mechanisms in Japanese encephalitis virus infection: effect on transcription of pattern recognition receptors in mouse neuronal cells and brain tissue. AB - Very little information is available on the role of innate immune mechanisms in Japanese encephalitis virus (JEV) infection. This study was designed to investigate the role of all Pattern Recognition Receptors (PRRs) in JEV infection in a mouse neuronal cell line in comparison to events that occur in vivo, using JEV infected suckling and adult mice. Analysis of mRNA expression was carried out using RT-PCR for detection of PRR genes and their downstream pathway genes, while a PCR array technique was used to examine the complete transcription analysis. Amongst the various innate immune receptors, TLR3 gene exhibited differential expression in JEV-infected Neuro2a, in suckling mice and adult mouse brain cells but not in uninfected control cells. The downstream events of TLR3 were confirmed by increased mRNA expression of IRF3 and interferon-beta in JEV-infected Neuro2a cells and suckling mice brain tissue. To confirm the functional significance of this observation, TLR3 gene silencing experiments were carried using specific siRNA in Neuro2a cells. The results revealed a significant enhancement of JEV replication in TLR3 gene silenced JEV-infected Neuro2a cells, thereby suggesting that TLR3 serves a protective role against JEV. The expression levels of other PRRs varied. JEV-infected adult mice showed significant upregulation of TLR2 and MDA5 as compared to JEV-infected suckling mice and Neuro2a cells. In addition, upregulation of Myd88 and IRF7 was also noted in adult mice. These observations, coupled with the fact that adult mice infected with JEV exhibited longer survival rates, suggests that the host antiviral TLR2 response seen in adult mice was eventually countered by the virus by using MDA5 receptor. Our findings suggest that different PRRs appear to be involved in JEV infection in Neuro2a cells and brains of suckling and adult mice. PMID- 24236858 TI - A forward osmosis-membrane distillation hybrid process for direct sewer mining: system performance and limitations. AB - This study demonstrates the robustness and treatment capacity of a forward osmosis (FO)-membrane distillation (MD) hybrid system for small-scale decentralized sewer mining. A stable water flux was realized using a laboratory scale FO-MD hybrid system operating continuously with raw sewage as the feed at water recovery up to 80%. The hybrid system also showed an excellent capacity for the removal of trace organic contaminants (TrOCs), with removal rates ranging from 91 to 98%. The results suggest that TrOC transport through the FO membrane is governed by "solute-membrane" interaction, whereas that through the MD membrane is strongly correlated to TrOC volatility. Concentrations of organic matter and TrOCs in the draw solution increased substantially as the water recovery increased. This accumulation of some contaminants in the draw solution is attributed to the difference in their rejection by the FO and MD systems. We demonstrate that granular activated carbon adsorption or ultraviolet oxidation could be used to prevent contaminant accumulation in the draw solution, resulting in near complete rejection (>99.5%) of TrOCs. PMID- 24236859 TI - N-acetylcysteine in contrast-induced acute kidney injury: clinical use against principles of evidence-based clinical medicine! AB - Contrast-induced acute kidney injury (CI-AKI) is one of the most widely discussed and debated topic in cardiovascular medicine and N-acetylcysteine (NAC) is the most widely used pharmacological agent assessed in clinical trials for offering renal protection against CI-AKI. Results of these clinical trials are though split between those that favor its use and vice versa. In this brief communication we discuss the latest research advances regarding the use of NAC against CI-AKI. Recent clinical evidence and overview of in-depth statistical analyses of relevant clinical trials and their meta-analyses do not support the use of NAC in prophylaxis against CI-AKI. Adequate hydration before and after contrast media exposure, along with avoidance of nephrotoxic drugs, remains the recommended prophylaxis against CI-AKI. PMID- 24236860 TI - The emerging science of consciousness: mind, brain, and the human experience. PMID- 24236861 TI - The thinking ape: the enigma of human consciousness. AB - What is the origin and nature of consciousness? If consciousness is common to humans and animals alike, what are the defining traits of human consciousness? Moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, Nobel laureate psychologist Daniel Kahneman, philosopher David Chalmers, expert in primate cognition Laurie Santos, and physician-scientist Nicholas Schiff discuss what it means to be conscious and examine the human capacities displayed in cognitive, aesthetic, and ethical behaviors, with a focus on the place and function of the mind within nature. The following is an edited transcript of the discussion that occurred October 10, 2012, 7:00-8:15 PM, at the New York Academy of Sciences in New York City. PMID- 24236862 TI - How can we construct a science of consciousness? AB - This chapter gives an overview of the projects facing a science of consciousness. Such a science must integrate third-person data about behavior and brain processes with first-person data about conscious experience. Empirical projects for integrating these data include those of contrasting conscious and unconscious processes, investigating the contents of consciousness, finding neural correlates of consciousness, and eventually inferring underlying principles connecting consciousness with physical processes. These projects are discussed with reference to current experimental research on consciousness. Some obstacles that a science of consciousness faces are also discussed. PMID- 24236863 TI - The mystery of memory: in search of the past. AB - A universal fascination with how we remember, forget, and create false memories cuts across the arts and sciences, as do the questions of how and where memories are formed and preserved. Moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, novelist and comparative literature professor Andre Aciman (City University of New York), neuroscientist Joseph LeDoux (New York University), psychologist Daniel Schacter (Harvard University), and historian of science and medicine Alison Winter (University of Chicago) discuss how memory impacts our perception of ourselves, the development of personality, and the ability to construct and reconstruct our past experience. The following is an edited transcript of the discussion that occurred November 14, 2012, 7:00 8:15 PM, at the New York Academy of Sciences in New York City. PMID- 24236864 TI - How memoirists mold the truth. PMID- 24236866 TI - Becoming conscious: the science of mindfulness. AB - Many of us go through our daily lives on autopilot, not fully aware of our conscious experiences. In a discussion moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, neuroscientists Richard Davidson and Amishi Jha and clinical mindfulness expert Jon Kabat-Zinn explore the role of consciousness in mental and physical health, how we can train our minds to be more flexible and adaptable, and cutting-edge neuroscience findings about the transformation of consciousness through mindfulness and contemplative practice. The following is an edited transcript of the discussion that occurred February 6, 2013, 7:00-8:15 PM, at the New York Academy of Sciences in New York City. PMID- 24236865 TI - Music and the mind: the magical power of sound. AB - Music has been a wonderful tool to investigate the interconnection between brain science, psychology, and human experience. Moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, cognitive neuroscientist and musician Jamshed Bharucha, music therapy pioneer Concetta Tomaino, jazz pianist Vijay Iyer, and physician musician Charles Limb discuss the neurological basis of creativity and aesthetic judgment and the capacity of music to elicit specific emotions and to heal the body. The following is an edited transcript of the discussion that occurred December 12, 2012, 7:00-8:15 PM, at the New York Academy of Sciences in New York City. PMID- 24236867 TI - Foreword to the emerging science of consciousness: mind, brain, and the human experience. PMID- 24236868 TI - Poly(thymine)-templated fluorescent copper nanoparticles for ultrasensitive label free nuclease assay and its inhibitors screening. AB - Noble-metal fluorescent nanoparticles have attracted considerable interest on account of their excellent properties and potential applicable importance in many fields. Particularly, we recently found that poly(thymine) (poly T) could template the formation of fluorescent copper nanoparticles (CuNPs), offering admirable potential as novel functional biochemical probes. However, exploration of poly T-templated CuNPs for application is still at a very early stage. We report herein for the first example to develop a novel ultrasensitive label-free method for the nuclease (S1 nuclease as a model system) assay, and its inhibitors screening using the poly T-templated fluorescent CuNPs. In this assay, the signal reporter of poly T of 30 mer (T30) kept the original long state in the absence of nuclease, which could effectively template the formation of fluorescent CuNPs. In the presence of nuclease, poly T was digested to mono- or oligonucleotide fragments with decrease of fluorescence. The proposed method was low-cost and simple in its operation without requirement for complex labeling of probe DNA or sophisticated synthesis of the fluorescent compound. The assay process was very rapid with only 5 min for the formation of fluorescent CuNPs. The capabilities for target detection from complex fluids and screening of nuclease inhibitors were verified. A high sensitivity exhibited with a detectable minimum concentration of 5 * 10(-7) units MUL(-1) S1 nuclease, which was about 1-4 orders of magnitude more sensitive than the developed approaches. PMID- 24236870 TI - The curious case of Yasmin((r)): when does a generic's label induce doctors to practice a patented method of use? PMID- 24236871 TI - Recent European legal developments on second medical uses and dosage regimes. PMID- 24236869 TI - An alternative approach to estimate age-related mortality of kidney transplant recipients compared to the general population: results in favor of old-to-old transplantations. AB - Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased-donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10-year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease. PMID- 24236872 TI - The Mayo v. Prometheus decision. PMID- 24236874 TI - Are natural products and medical diagnostic tests still eligible for patents in the USA? AB - In 2010, the biotechnology and molecular diagnostics industries were shocked by the decision from a US District Court to the effect that isolated endogenous DNA and diagnostic tests based on newly discovered DNA sequences were not eligible for US patents. The case related to the BRCA1/2 genes for breast and ovarian cancer. On appeal, the decision was almost entirely overturned. However, in March 2012, the US Supreme Court vacated the appeal court decision and instructed the appeals court to rehear the case in the light of its very recent decision, which suggested that products of nature and their obvious uses should not be patentable. This commentary explores the points at issue. PMID- 24236877 TI - 'Reference composition' not 'lead compound': recent developments in case law for obviousness of pharmaceutical composition claims. AB - For most chemical compound claims, the obviousness analysis begins with the identification of a 'lead compound'. Pursuant to a recent decision from the Federal Circuit, a similar framework is now applicable for pharmaceutical composition claims. In Unigene Labs v. Apotex (2011), the obviousness analysis for a claim covering a bioequivalent nasal spray was said to start with the identification of the 'reference composition'. The court reasoned that while a person of ordinary skill in the art would typically be motivated to develop a bioequivalent of a given US FDA-approved reference composition, such a new composition may still be non-obvious if the prior art does not teach which bioequivalent among a large number of possible formulations is the best or which ingredient(s) may be substituted for others. A review of the case law reveals that the "reference composition" framework is neither entirely new nor universally applicable to all obviousness challenges to pharmaceutical composition claims. Even so, the Unigene decision appears to signal the court's preference for this framework and will likely employ it wherever it is appropriate to do so. PMID- 24236878 TI - How do patent rights affect regulatory approvals and data exclusivity rights for pharmaceuticals in the EU? AB - This article sheds light on the relationship, or rather, absence of a relationship, between patent rights and regulatory approval procedures in the EU. The principle of 'patent linkage' has long been recognized and applied by regulatory authorities in the USA. The European Commission, however, opposes the idea of linking patent rights to marketing authorizations and pricing and reimbursement decisions. This position is grounded in Article 126 of Directive 2001/83 and is expected not to change anytime soon, given the clear reaffirmation thereof in the recent Sector Inquiry Report and Transparency Directive Proposal. Therefore, the European Medicines Agency or national authorities are not permitted to refuse approval and, likely, pricing and reimbursement of a generic when the innovative reference product is still protected by a patent. The authors, however, advocate that there are strong legal arguments for patent holders to challenge regulatory decisions that did not respect their patent rights before the competent national courts. PMID- 24236879 TI - Differentiating stem cell patents. AB - Stem cells are defined by their capability for both self-renewal through cell division and for producing a lineage capable of differentiating into one or more specialized cell types. Stem cells are found both in adult tissues and in the developing embryo. While embryonic stem cells are able to differentiate into each and every cell type, adult stem cells are generally only able to form the cell types of the organ from which they originate. Stem cells are essential for the renewal and repair of human tissues and have been at the centre of research into regenerative medicine. They have also emerged as a valuable tool for drug discovery and development. Strong patent protection is a crucial driver of investment into new stem cell technologies. However, their special nature has created a number of uncertainties. In particular, the biological potential of embryonic stem cells to create new human life raised ethical concerns and caused boundaries to be set on the scope of patentability. The bar has been set at different places in the USA, Europe and Canada. Careful assessment of the options for protection in these jurisdictions is necessary in order to manage risk and maximize rewards. This article provides an overview of the patentability of stem cells with a focus on recent developments regarding embryonic, adult and induced pluripotent stem cells. PMID- 24236880 TI - Obtaining, challenging and enforcing pharmaceutical patents under the America Invents Act. AB - The America Invents Act (AIA) will affect how intellectual property rights for pharmaceutical innovations are obtained, challenged and enforced. For example, the AIA allows pharmaceutical companies to take a more uniform approach in seeking patent protection worldwide. Post-grant and inter partes review procedures in the USPTO will allow patents to be challenged by pharmaceutical interests at a lower cost than that of litigation in US courts, and should improve the quality of patents as a whole. Provisions in the AIA incentivize pharmaceutical companies to monitor the published applications and patents of competitors, and to make prompt challenges to patentability where appropriate, promoting the integrity of the intellectual property landscape. PMID- 24236881 TI - Patent term extensions: issues, challenges and implications for pharmaceuticals. AB - The standard term of a patent is 20 years from the date of filing. However, the time required for a pharmaceutical product to pass through research and development, and clinical trials to obtain regulatory approval can often be more than 10 years. This effectively shortens the life of the patent leaving the patentee with little or no monopoly over the pharmaceutical product by the time it reaches market. The solution to this loss of patent monopoly in many countries is to provide an extension to compensate for loss of patent term due to obtaining regulatory approval of a product. This article provides a summary of some of the issues, challenges and implications of patent term extensions in various countries. PMID- 24236882 TI - Clearing the fog: patenting trends for the treatment of Alzheimer's disease. AB - This article asks, "What can Network Patent AnalysisTM (NPA) tell us about developments in the treatment of this serious condition?" Patents filed for the treatment of Alzheimer's disease have been analyzed by NPA. NPA is an unique patent analysis method that maps the 'collective intelligence' of the patent applicants to group and rank patents, technologies and patent applicants. A search for Alzheimer's disease patents identified approximately 24,000 patents, to which we added 24,000 citationally connected patents. NPA identified the leading 2,153 patents in the combined 48,000 patents and grouped most of these 2153 patents into 23 subject clusters. The 23 clusters of patents fall into two major groupings: drugs targeted to the beta-amyloid protein ('amyloid grouping'); and drugs targeted to the Tau/serotonin and other alternative pathways ('Tau grouping'). Filing activity for the 2153 strongest patents peaked between the year 2000 and 2005. This, along with the broad range of subject matter in the patent clusters, suggests that Alzheimer's disease treatments are still undergoing strong development. PMID- 24236883 TI - Novel serine protease inhibitors. AB - The pursuit of serine protease inhibitors as anticoagulants and anti-hepatitis C virus drugs continues to be an active area of research. Compounds such as P1-P3 macrocyclic peptides and linear peptides have been registered as potent hepatitis C virus protease inhibitors and compounds such as phenylglycinamide derivatives, substituted biaryls, tetrahydroquinoline derivatives, arylpropionamides, arylacrylamides, arylpropynamides, arylmethylurea analogs and peptides as factor XIa inhibitors. Given the recent US FDA approval of telaprevir and boceprevir for the treatment of hepatitis C virus, the development of new serine protease inhibitors is likely to be one of the hottest areas in the pharmaceutical industry. This review covers the patent literature on serine protease inhibitors during the period between 2009 and 2010. PMID- 24236884 TI - Triple monoamine uptake inhibitors. AB - Agents interfering with the reuptake of catecholamines and tryptamines are well known drugs capable of treating serious illnesses, including depression, pain and dependence. Further therapeutic applications and use have been tested and an increase in the variety of the chemical templates has been achieved in the last few years. This review attempts to give an organic overview of molecules capable of simultaneously interfering with the reuptake of all the three major monoamine neurotransmitters (dopamine, norepinephrine/noradrenaline and serotonin). PMID- 24236885 TI - Small molecules as pro-apoptotic anticancer agents. AB - The quest for potent and selective targeted therapies in anticancer research is taking advantage of apoptosis-related mechanisms of action to identify a number of novel clinical candidates. This review is chemically focused on small molecules and deals with five target families that influence caspase-dependent apoptosis: caspase-3, Bcl-2 and IAP protein family members, p53 and the proteasome. Each target class is briefly described at first in terms of its involvement and relevance in tumor initiation and progression. Drug candidates currently undergoing clinical trials are then presented for each target class, followed by a quick summary of target-modulating chemotypes that have appeared in patent literature since 2006. Finally, future trends likely to become significant in apoptosis-targeted cancer therapies are presented and discussed. PMID- 24236887 TI - Physically based groundwater vulnerability assessment using sensitivity analysis methods. AB - A general physically based method is presented to assess the vulnerability of groundwater to external pressures by numerical simulation of groundwater flow. The concept of groundwater vulnerability assessment considered here is based on the calculation of sensitivity coefficients for a user-defined groundwater state for which we propose several physically based indicators. Two sensitivity analysis methods are presented: the sensitivity equation method and the adjoint operator method. We show how careful selection of a method can significantly minimize the computational effort. An illustration of the general methodology is presented for the Herten aquifer analog (Germany). This application to a simple, yet insightful, case demonstrates the potential use of this general and physically based vulnerability assessment method to complex aquifers. PMID- 24236889 TI - Bifunctional oligodeoxynucleotide/antagomiR constructs: evaluation of a new tool for microRNA silencing. AB - MicroRNAs (miRNAs) are fine-tuners in cellular processes, including those of the immune response. To study their functions and effects in immune cells, it is necessary to achieve specific silencing of individual miRNAs. To date, introduction of antisense microRNAs (antagomiRs) into primary cells is based on electroporation, lipofection, and viral vectors. However, these techniques often compromise viability, proliferative capacity, and differentiation. Furthermore, efficiency varies depending on the cell type and some are not suitable for in vivo approaches. To overcome these limitations we exploited the property of phosphorothioate (PTO)-modified DNA oligodeoxynucleotides (ODN) to enter cells with high efficacy: we developed and evaluated ODN/antagomiR constructs that consist of a PTO-ODN carrier covalently linked to a fully methylated antagomiR RNA sequence. Using these constructs, we achieved transfection efficiency of approximately 99% in leukocytes-in particular, in B lymphocytes that are hard to transfect with other methods. Our data demonstrate that miRNA silencing by the antagomiR portion of the constructs was specific and efficient, which could be further confirmed by an increase in target protein under silencing conditions. The constructs were successfully tested in human B cells, plasmacytoid dendritic cells, monocytes, and monocyte-derived dendritic cells, thus demonstrating their versatility. Moreover, introduction of stimulatory CpG sequences into the ODN portion conveys immune stimulatory quality when intended. Thus, bifunctional ODN/antagomiR constructs represent a highly efficient, versatile, and easy-to handle tool to manipulate cellular miRNA expression levels and to allow the subsequent investigation of specific miRNA functions. PMID- 24236888 TI - Differential role of D1 and D2 receptors in the perifornical lateral hypothalamus in controlling ethanol drinking and food intake: possible interaction with local orexin neurons. AB - BACKGROUND: The neurotransmitter dopamine (DA), acting in various mesolimbic brain regions, is well known for its role in promoting motivated behaviors, including ethanol (EtOH) drinking. Indirect evidence, however, suggests that DA in the perifornical lateral hypothalamus (PF/LH) has differential effects on EtOH consumption, depending on whether it acts on the DA 1 (D1) or DA 2 (D2) receptor subtype, and that these effects are mediated in part by local peptide systems, such as orexin/hypocretin (OX) and melanin-concentrating hormone (MCH), known to stimulate the consumption of EtOH. METHODS: The present study in brain-cannulated Sprague-Dawley rats measured the effects of dopaminergic compounds in the PF/LH on drinking behavior in animals trained to consume 7% EtOH and also on local peptide mRNA expression using digoxigenin-labeled in situ hybridization in EtOH naive animals. RESULTS: Experiments 1 and 2 showed that the D1 agonist SKF81297 (10.8 nmol/side) in the PF/LH significantly increased food intake, while tending to increase EtOH intake, and the D1 antagonist SCH23390 significantly decreased EtOH intake without affecting food intake. In contrast, the D2 agonist quinelorane (6.2 nmol/side) in the PF/LH significantly reduced EtOH consumption, while the D2 antagonist sulpiride increased it. Experiments 3 and 4 revealed differential effects of PF/LH injection of the DA agonists on local OX mRNA, which was increased by the D1 agonist and decreased by the D2 agonist. These DA agonists had no impact on MCH expression. CONCLUSIONS: These results support a stimulatory role of the PF/LH D1 receptor in promoting the consumption of both EtOH and food, in contrast to a suppressive effect of the D2 receptor on EtOH drinking. They further suggest that these receptors affect consumption, in part, through local OX-expressing neurons. These findings provide new evidence for the function of PF/LH DA receptor subtypes in controlling EtOH and food intake. PMID- 24236890 TI - MicroRNA-29b modulates Japanese encephalitis virus-induced microglia activation by targeting tumor necrosis factor alpha-induced protein 3. AB - Japanese encephalitis virus (JEV), a single-stranded RNA (ssRNA) virus, is the leading cause of encephalitis in Asia. Microglial activation is one of the key events in JEV-induced neuroinflammation. Although the various microRNAs (miRNAs) has been shown to regulate microglia activation during pathological conditions including neuroviral infections, till date, the involvement of miRNAs in JEV infection has not been evaluated. Hence, we sought to evaluate the possible role of miRNAs in mediating JEV-induced microglia activation. Initial screening revealed significant up-regulation of miR-29b in JEV-infected mouse microglial cell line (BV-2) and primary microglial cells. Furthermore, using bioinformatics tools, we identified tumor necrosis factor alpha-induced protein 3, a negative regulator of nuclear factor-kappa B signaling as a potential target of miR-29b. Interestingly, in vitro knockdown of miR-29b resulted in significant over expression of tumor necrosis factor alpha-induced protein 3, and subsequent decrease in nuclear translocation of pNF-kappaB. JEV infection in BV-2 cell line elevated inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokine expression levels, which diminished after miR-29b knockdown. Collectively, our study demonstrates involvement of miR-29b in regulating JEV- induced microglial activation. PMID- 24236891 TI - Rice consumption and urinary concentrations of arsenic in US adults. AB - Exposure to inorganic arsenic in the general population occurs mainly from drinking water and food sources. This study examined the association between rice consumption and urinary concentrations of arsenic in US adults, aged 20-85 years, in the 2003-2006 National Health and Nutrition Examination Survey. Significantly higher geometric means of creatinine-corrected urinary concentrations of total arsenic (TAs) and dimethylarsinic acid (DMA) were found in participants who consumed rice more than twice per week, compared to the reference group. Multivariate logistic regression analysis revealed a statistically significant association between rice consumption and urinary concentrations of TAs [odds ratio (OR) = 1.51 (1.08, 2.09)] and DMA [OR = 2.24 (1.57, 3.21)] after adjustment for demographic variables, seafood intake (the main source of organic arsenic), and source of drinking water. Furthermore, significant variations in rice consumption and urinary concentrations of arsenic were observed in different racial groups. This study demonstrated that rice consumption contributed to inorganic arsenic exposure in US adults. PMID- 24236892 TI - MALDI-TOF MS for identification of porcine Brachyspira species. AB - The aim of this study consisted in evaluating MALDI-TOF MS as a tool for the identification of the genus Brachyspira (B.) and its relevant species for the pig industry. First, a database was created with 30 control strains, and superspectra for five different porcine Brachyspira species were calculated. In a second step, 67 field isolates were investigated using MALDI-TOF MS, and results were compared to those obtained using nox gene-based RFLP (reference method) and biochemical tests. Among the 67 field isolates, five different Brachyspira species were detected using nox gene-based RFLP analysis. MALDI-TOF MS analysis correctly assigned all isolates to the genus Brachyspira and identified all isolates from B. hyodysenteriae (29/29), B. pilosicoli (11/11), B. intermedia (4/4) and B. innocens (11/11). In terms of B. murdochii, MALDI-TOF MS assigned one of 12 isolates ambiguously as B. innocens/B. murdochii. The results of this study indicate that MALDI-TOF MS facilitates the diagnosis of swine dysentery and porcine intestinal spirochaetosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Current methods for the discrimination of pathogenic Brachyspira hyodysenteriae and Brachyspira pilosicoli from Brachyspira species with low pathogenic potential have proven to be laborious and time-consuming and are therefore not suitable for routine diagnostics. This study describes the evaluation of MALDI-TOF MS for the identification of different porcine Brachyspira species in routine diagnostic laboratories. The results suggest that MALDI-TOF MS is an effective method for the identification of porcine Brachyspira spp. and accelerates diagnosis of swine dysentery and porcine intestinal spirochaetosis. PMID- 24236894 TI - The importance of proper administration and interpretation of neuropsychological baseline and postconcussion computerized testing. AB - Media coverage, litigation, and new legislation have resulted in a heightened awareness of the prevalence of sports concussion in both adult and youth athletes. Baseline and postconcussion testing is now commonly used for the assessment and management of sports-related concussion in schools and in youth sports leagues. With increased use of computerized neurocognitive sports concussion testing, there is a need for standards for proper administration and interpretation. To date, there has been a lack of standardized procedures by which assessments are administered. More specifically, individuals who are not properly trained often interpret test results, and their methods of interpretation vary considerably. The purpose of this article is to outline factors affecting the validity of test results, to provide examples of misuse and misinterpretation of test results, and to communicate the need to administer testing in the most effective and useful manner. An increase in the quality of test administration and application may serve to decrease the prevalence of invalid test results and increase the accuracy and utility of baseline test results if an athlete sustains a concussion. Standards for test use should model the American Psychological Association and Centers for Disease Control and Prevention guidelines, as well as the recent findings of the joint position paper on computerized neuropsychological assessment devices. PMID- 24236893 TI - Infections and their role in childhood asthma inception. AB - The association of early-onset wheezing with common viral and bacterial infections has raised significant interest in the role of infections in childhood asthma inception. This article serves to review these relationships among infections, host factors, and asthma inception in childhood. PMID- 24236895 TI - Circumstances, experiences and processes surrounding women's entry into sex work in India. AB - Evidence suggests that in India, the early stages of a woman's career as a sex worker may be an important period to target for HIV and sexually transmitted infection prevention. Before such an intervention is designed and implemented, it is necessary to first understand the life circumstances of women at the start of their sex work careers. We performed a review to bring together available literature pertaining to entry into sex work in India and to highlight knowledge gaps. We found that historical traditions of dedication into sex work, financial insecurity, family discord, violence and coercion, and desire for financial independence are commonly reported reasons for entering into sex work. We also found that families and the broader sex worker community play an important role in the early stages of a woman's sex work career. We suggest that HIV-prevention programmes in India would substantially benefit from a deeper understanding of the life circumstances of new and young women sex workers. Further research should be conducted focusing on family and community involvement in women's entry into sex work, and on the important period of time after a woman's first commercial sex encounter, but before self-identification as a sex worker. PMID- 24236896 TI - The t(14;18)(q32;q21)/IGH-MALT1 translocation in gastrointestinal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). AB - AIMS: Studies have indicated that the t(14;18)(q32;q21)/IGH-MALT1 translocation is present in extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). However, only a few studies have investigated the incidence of t(14;18)/IGH-MALT1 in primary gastrointestinal MALT lymphomas or in diffuse large B-cell lymphomas (DLBCL). The overall significance of t(14;18)/IGH MALT1 in gastrointestinal MALT lymphomas is not clear. We examined 41 gastrointestinal MALT lymphoma and 23 DLBCL cases, with the aim of further understanding the role of t(14;18)/IGH-MALT1 in these diseases. METHODS AND RESULTS: Fluorescence in-situ hybridization (FISH) assays for the detection of t(14;18)/IGH-MALT1 and t(11;18)(q21;q21)/API2-MALT1, along with immunostaining and histological evaluations, were performed on selected cases. Of the 64 analysed cases, one gastric MALT lymphoma and one colonic MALT lymphoma were positive for t(14;18)/IGH-MALT1. CONCLUSIONS: We describe what are, to our knowledge, the first reported primary colonic MALT lymphoma carrying t(14;18)(q32;q21)/IGH-MALT1, and one of the few reported cases of gastric MALT lymphoma with this translocation. As this translocation is seen in only a few gastrointestinal MALT lymphomas, it is not useful as a diagnostic marker for routine clinical services. Although these findings suggest that t(14;18)/IGH MALT1 is a rare molecular event in gastrointestinal MALT lymphomas and DLBCLs, further studies to elucidate the role of this genetic alteration in these diseases are indicated. PMID- 24236897 TI - The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders. AB - AIMS: Given that sleep disorders are known to be related to insulin resistance, and metformin has favourable effects on insulin resistance and on ventilatory drive, we sought to determine whether metformin therapy was related to sleep variables in a group of patients with Type 2 diabetes. METHODS: We performed a retrospective, observational study of our centre's database for patients referred for potential sleep disorders and then compared metformin-treated patients with those not treated with the drug. All study patients had undergone the same standard polysomnographic procedure. A multivariate analysis was performed to establish whether or not there was an independent relationship between metformin use and sleep variables (after adjusting for age, gender, BMI, neck circumference, cumulated risk factors and insulin use). RESULTS: We studied 387 patients (mean +/- sd age: 58.4 +/- 10.8 years), of whom 314 had been treated with metformin. Total sleep time and sleep efficiency were higher in metformin treated patients than in patients not treated with metformin [total sleep time: 6 h 39 min vs. 6 h 3 min, respectively (P = 0.002); sleep efficiency: 77.9 +/- 12.3 vs. 71.5 +/- 17.2%, respectively (P = 0.003)]. These differences persisted after adjustment for covariates and were observed even although metformin users had a higher BMI than did non-users (median 37.5 vs. 34.8 kg/m(2) ; P = 0.045). CONCLUSION: We showed that metformin therapy is associated with a longer sleep duration and better sleep efficiency. Randomized clinical trials are needed to confirm metformin's favourable effect on sleep quality and quantity. PMID- 24236898 TI - The background to this themed issue on neuropeptides. AB - A meeting of the British Pharmacological Society in association with the European Neuropeptide Club and Americal Summer Neuropeptide Conference in June 2012 led to this themed issue on neuropetides. A wide range of neuropeptides are discussed, in various physiological and pathophysiological conditions, with respect to their upstream and downstream pathways. It is clear, at this point in time, that targeting neuropeptides has therapeutic potential in pathologies ranging from migraine to obesity. It is also clear from the reviews in this issue of the British Journal of Pharmacology that there is still so much to learn. LINKED ARTICLES: This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue 7. PMID- 24236899 TI - Connecting type 2 diabetes to Alzheimer's disease. PMID- 24236901 TI - Prolonged-release fampridine improves walking in a proportion of patients with multiple sclerosis. AB - Fampridine is indicated to improve walking in adult multiple sclerosis (MS) patients. Indications vary between countries and the prescribing neurologist should be aware of the labeling and indication in his own country. The prolonged release formulation of 4-aminopyridine has reduced the risk of seizure to a level near the intrinsic MS risk, and the risk can be further minimized if it emphasized that patients should not exceed the recommended dose of 10 mg twice a day, should not catch up on missed doses and should not divide, crush or chew tablets. It is imperative to check the renal function before and during treatment and make sure the patient does not get concomitant medications affecting the renal elimination. The use of fampridine is considered safe, and the side effects are often mild and acceptable. Approximately one-third of MS patients treated with fampridine will experience an improvement of their walking speed above 20% on the timed 25-foot walk test (T25FW), which is considered to be clinically relevant. PMID- 24236902 TI - Effects of rotigotine transdermal system on non-motor symptoms in Parkinson's disease: an overview. AB - Parkinson's disease (PD) is a progressive neurodegenerative disease, involving the dopaminergic, noradrenergic, serotonergic and cholinergic systems. In addition to its cardinal motor symptoms, PD is associated with a diverse range of non-motor symptoms (NMS) that may be more important than motor symptoms. Although there is evidence for a dopaminergic contribution for several NMS in PD, NMS have been underrecognized and undertreated by clinicians. There is evidence that dopaminergic therapy, including dopamine agonists, may alleviate some NMS, such as anxiety and depression. This review focuses on published data on the effects of the non-ergoline dopaminergic agonist rotigotine transdermal system in the treatment of NMS in patients with PD. Data on the effects of orally administered non-ergoline agonists, including ropinirole and pramipexole, on NMS are also summarized. PMID- 24236903 TI - Increasing awareness of sudden unexpected death in epilepsy. AB - Epilepsy affects about 1 in 130 people in the UK and most have a normal life expectancy. Sudden unexpected death in epilepsy (SUDEP) is a - probably heterogeneous - condition where patients with epilepsy die suddenly, almost certainly during a seizure and with no other identified cause of death. The mechanism(s) of SUDEP remain uncertain, but with a growing international scientific interest, there is reason to be optimistic that eventually most of the likely several causes will be identified. Increasing awareness of SUDEP has generated efforts to understand the underlying pathophysiology of SUDEP better to direct the search for effective preventative measures. This review addresses the epidemiology of SUDEP, its possible underlying mechanisms, risk factors, clinical implications and future directions for research. PMID- 24236904 TI - Understanding the spectrum of temporal lobe epilepsy: contributions for the development of individualized therapies. AB - Mesial temporal lobe epilepsy (TLE) is a subtype of epilepsy in which individuals present with seizure semiology and electroencephalographic characteristics that point to an ictal onset in mesial temporal structures. The diagnosis of TLE involves different etiologies, the most common being hippocampal sclerosis, but up to 20% of TLE patients have no detectable structural lesions on modern MRIs. A variability of antiepileptic drug response and surgical prognosis is observed in TLE. The understanding of the differences among patients with TLE can facilitate the development of individualized and more efficient therapeutics. In this study, we will address the recent contributions of neuroimaging, neurophysiology, genetics and histopathology to the comprehension of the spectrum of TLE with and without MRI signs of hippocampal sclerosis and how the advances in these areas have helped to improve surgical treatments. PMID- 24236905 TI - Understanding the relationship between smoking and pain. AB - This review provides an overview of evidence regarding several key mechanisms pertinent to understanding the co-occurrence of smoking dependence and pain, both potentially costly conditions, and highlights treatment implications and future research directions. We describe each of pain and smoking dependence and introduce a revised integrative reciprocal model that explains their co occurrence. We then provide a selective review of evidence pertinent to direct and indirect pathways between variables postulated in the model. We also provide general recommendations for improving assessment and treatment of smokers with clinically significant pain. We conclude with a targeted agenda for future investigation of the co-occurrence of smoking and pain. Empirical efforts directed at testing postulates of the proposed integrative model may yield a better understanding of the nature of the relationship between these prevalent and costly health conditions as well as evidence-based preventive and treatment strategies for people who experience nicotine dependence and pain-related disability. PMID- 24236906 TI - Psychiatric consultations and therapy recommendations following a suicide attempt in a general hospital and their associations with selected parameters in a 1-year period. AB - OBJECTIVE: Our study aims to determine the frequency and distribution of suicide attempts according to the patients' characteristics and type of suicide attempt as well as the method of treatment proposed by the consultation-liaison service in a general hospital. METHODS: This retrospective naturalistic study covers a 1 year period (2012), during which 51 suicide attempters were hospitalised in the Charite Berlin, Campus Benjamin Franklin, Germany. The following data were analysed: method of suicide, account of prior psychiatric history and medication, as well as the acute psychiatric diagnosis and treatment - including pharmacotherapy. RESULTS: Most of the patients were diagnosed with a psychiatric illness. Major depressive disorder was the most frequent diagnosis in consultation. Treatment recommendations more often entailed further psychiatric treatment than medication. In the cases where medication was indeed given, benzodiazepines were the most frequently prescribed. CONCLUSIONS: Most of the suicide attempters needed further therapy in psychiatric hospitals. A specialised pharmacotherapy (antidepressants, mood stabilisers) was rarely recommended by the psychiatric consultation service. The psychiatric consultation and therapy recommendations are important in guiding future acute treatment procedures. PMID- 24236907 TI - Sex and age differences in symptoms in borderline personality symptomatology. AB - OBJECTIVE: Variations in the symptoms of borderline personality disorder (BPD) as a function of sex and age remain unclear. In this study, we examined sex and age differences with regard to various symptoms encountered in BPD. METHODS: Using a compilation of four samples, all cross-sectional from the same recruitment site and with identical self-report measures for borderline personality symptomatology (BPS), we examined sex- and age-related differences with regard to borderline personality among 1,503 primary care patients. RESULTS: Men and women did not differ significantly in their overall scores or rates of BPS. With regard to sex differences in symptoms among respondents with substantial BPS, engagement in sexually abusive relationships was more common among women than men. Overall scores and rates of BPS were greater among younger respondents compared to older respondents. With regard to age differences among those with substantial BPS, self-cutting and scratching were more common in younger individuals whereas finding life dull and meaningless was more common among older individuals. CONCLUSIONS: There appear to be few overall symptomatic differences among individuals with borderline personality with regard to sex and age. PMID- 24236908 TI - The prevalence and recognition rate of delirium in hospitalized elderly patients in Turkey. AB - OBJECTIVE: Delirium is frequently observed, but generally under recognized in elderly hospitalized patients. The aims of this study were to determine the prevalence of delirium in elderly patients hospitalized at a university hospital, and to determine the recognition rate by hospital staff during hospitalization. METHODS: The study included 108 consecutive patients aged >= 65 years that were hospitalized in the medical and surgical inpatient departments at Baskent University Hospital, Ankara, Turkey. All the patients were evaluated using the Mini Mental State Examination (MMSE) upon admission and Confusion Assessment Method (CAM) on a daily basis during hospitalization. Written documents and consultation requests from psychiatry and/or neurology departments were reviewed for recognition of delirium by hospital staff. RESULTS: Among the 108 patients in the study, delirium was noted in 18 (16.7%) during their hospital stay. Consultation from psychiatry or neurology departments was requested for 5 of the 18 patients, only 1 with a delirium diagnosis, indicating that 17 of the cases (94.4%) were not recognized by their primary physicians. CONCLUSIONS: The delirium non-recognition rate in elderly hospitalized patients was very high. We think that hospital staff must be trained to recognize the symptoms of delirium and identify high-risk patients. PMID- 24236909 TI - iRGD conjugated TPGS mediates codelivery of paclitaxel and survivin shRNA for the reversal of lung cancer resistance. AB - Multidrug resistance (MDR) is one of the major obstacles in tumor treatment. Herein, we reported an active targeting strategy with peptide-mediated nanoparticles deep into tumor parenchyma, which iRGD conjugated d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) mediated codelivery of paclitaxel (PTX) and survivin shRNA (shSur) for the reversal of lung cancer resistance. Pluronic P85-polyethyleneimine/TPGS complex nanoparticles incorporated with iRGD-TPGS conjugate codelivering PTX and shSur systems (iPTPNs) could induce effective cellular uptake, RNAi effects, and cytotoxicity on A549 and A549/T cells. In particular, iPTPNs showed superiority in biodistribution, survivin expression, tumor apoptosis, and antitumor efficacy by simultaneously exerting an enhanced permeability and retention (EPR) effect and iRGD mediated active targeting effects. iPTPNs significantly enhanced the accumulation of PTX and shSur, down-regulated survivin expression, and induced cell apoptosis in tumor tissue. The in vivo antitumor efficacy showed the tumor volume of iPTPNs group (10 mg/kg) was only 12.7% of the Taxol group. Therefore, the iRGD mediated PTX and shSur codelivery system could be a very powerful approach for the reversal and therapy of lung cancer resistance. PMID- 24236910 TI - Cervical auscultation as an adjunct to the clinical swallow examination: a comparison with fibre-optic endoscopic evaluation of swallowing. AB - This prospective, single-blinded study investigated the validity and reliability of cervical auscultation (CA) under two conditions; (1) CA-only, using isolated swallow-sound clips, and (2) CSE + CA, using extra clinical swallow examination (CSE) information such as patient case history, oromotor assessment, and the same swallow-sound clips as condition one. The two CA conditions were compared against a fibre-optic endoscopic evaluation of swallowing (FEES) reference test. Each CA condition consisted of 18 swallows samples compiled from 12 adult patients consecutively referred to the FEES clinic. Patients' swallow sounds were simultaneously recorded during FEES via a Littmann E3200 electronic stethoscope. These 18 swallow samples were sent to 13 experienced dysphagia clinicians recruited from the UK and Australia who were blinded to the FEES results. Samples were rated in terms of (1) if dysphagic, (2) if the patient was safe on consistency trialled, and (3) dysphagia severity. Sensitivity measures ranged from 83-95%, specificity measures from 50-92% across the conditions. Intra-rater agreement ranged from 69-97% total agreement. Inter-rater reliability for dysphagia severity showed substantial agreement (rs = 0.68 and 0.74). Results show good rater reliability for CA-trained speech-language pathologists. Sensitivity and specificity for both CA conditions in this study are comparable to and often better than other well-established CSE components. PMID- 24236911 TI - Moving beyond behaviour-only assessment: incorporating biomarkers to improve the early detection and diagnosis of autism spectrum disorders. AB - This paper presents a response to the Camarata (2014) lead article regarding the accuracy and effectiveness of early identification and early intervention for young children with autism spectrum disorders (ASD). While Caramata focused heavily on the challenges of behavioural screening for ASD, we believe that he has overlooked the potential that the identification of ASD biomarkers may have for the early detection of the disorder. We propose that the discovery of biomarkers, particularly those that may be used in conjunction with behavioural screening, may provide an important next step in reliably detecting and accurately diagnosing ASD in the early years. This would have important clinical implications in terms of providing early intervention, which may alter the developmental path for the child. PMID- 24236912 TI - Predicting reading outcomes in the classroom using a computer-based phonological awareness screening and monitoring assessment (Com-PASMA). AB - The screening and monitoring of phonological awareness (PA) in the classroom is of great importance to the early identification and prevention of reading disorder. This study investigated whether a time-efficient computer-based PA screening and monitoring assessment (Com-PASMA) could accurately predict end-of year reading outcomes for 5-year-old children in the first year of schooling. A longitudinal design was employed where the Com-PASMA was used to measure the PA ability of 95 5-year-old children at the start, middle, and end of the first year of school. Of this group, 21 children presented with spoken language impairment. Reading outcomes were formally measured after 1 year of schooling. School-entry measures of PA using the Com-PASMA (p < .001), in conjunction with language ability (p = .004), accounted for 68.9% of the variance in end-of-year word decoding ability. Sensitivity and specificity calculations demonstrated that the Com-PASMA was 92% accurate at school-entry, and 94% accurate by the middle of the school year in predicting reading outcomes at 6-years of age. Results suggest that a time-efficient computer-based method of screening and monitoring PA can support the early identification of reading difficulties in the first year of schooling. PMID- 24236914 TI - Ordered mesoporous carbon electrodes for Li-O2 batteries. AB - Ordered mesoporous carbon (OMC) with highly ordered pore channels was applied as an oxygen-side electrode for a Li-O2 battery. To evaluate the effect of the pore channel size on battery performance, we employed OMCs possessing two different pore sizes (6 and 17 nm). When cycled at a current density of 200 mA g(-1)carbon, the OMC electrodes reduced polarization in the oxygen evolution reaction by 0.1 V compared to those consisting of conventional super P carbon electrode. X-ray diffraction and transmission electron microscopy of the discharged oxygen electrodes provided evidence for the formation of amorphous Li2O2, a product of the oxygen reduction reaction, inside the OMC pores rather than on the electrode surface as in the case of the super P electrode. The OMC electrodes were also effective at high current densities (500 mA g(-1)carbon and 1000 mA g(-1)carbon). PMID- 24236913 TI - Posterior parietal cortex is critical for the encoding, consolidation, and retrieval of a memory that guides attention for learning. AB - Within most contemporary learning theories, reinforcement prediction error, the difference between the obtained and expected reinforcer value, critically influences associative learning. In some theories, this prediction error determines the momentary effectiveness of the reinforcer itself, such that the same physical event produces more learning when its presentation is surprising than when it is expected. In other theories, prediction error enhances attention to potential cues for that reinforcer by adjusting cue-specific associability parameters, biasing the processing of those stimuli so that they more readily enter into new associations in the future. A unique feature of these latter theories is that such alterations in stimulus associability must be represented in memory in an enduring fashion. Indeed, considerable data indicate that altered associability may be expressed days after its induction. Previous research from our laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event, and to the subsequent expression of that altered associability in more rapid learning. Here, for the first time, we identified a brain region, the posterior parietal cortex, as a potential site for a memorial representation of altered stimulus associability. In three experiments using rats and a serial prediction task, we found that intact posterior parietal cortex function was essential during the encoding, consolidation, and retrieval of an associability memory enhanced by surprising omissions. We discuss these new results in the context of our previous findings and additional plausible frontoparietal and subcortical networks. PMID- 24236916 TI - Communicating the needs of businesses to patent analysts. PMID- 24236915 TI - Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats. AB - Suberoylanilide hydroxamic acid (SAHA), or vorinostat, is a histone deacetylase inhibitor approved for use as chemotherapy for lymphoma in humans. The goal of this study was to establish pharmacological parameters of SAHA in cats. Our interest in treating cats with SAHA is twofold: as an anticancer chemotherapeutic and as antilatency therapy for feline retroviral infections. Relying solely on data from studies in other animals would be inappropriate as SAHA is partially metabolized by glucuronidation, which is absent in feline metabolism. SAHA was administered to cats intravenously (2 mg/kg) or orally (250 mg/m2, ~17 mg/kg) in a cross-over study design. Clinically, SAHA was well tolerated at these dosages as no abnormalities were noted following administration. The pharmacokinetics of SAHA in cats was found to be similar to that of dogs, but the overall serum drug exposure was much less than that of humans at an equivalent dose. The pharmacodynamic effect of an increase in acetylated histone proteins in blood was detected after both routes of administration. An increased oral dose of 60 mg SAHA/kg administered to one animal resulted in a surprisingly modest increase in peak drug concentration, suggesting possible saturation of absorption kinetics. This study provides a foundation for future studies of the clinical efficacy of SAHA in treating feline disease. PMID- 24236917 TI - Patents and the US FDA's definition of 'cocrystal': an ordinary and customary meaning? PMID- 24236918 TI - Additional protection for second medical uses of known drugs? PMID- 24236919 TI - Patentability of stem cells in Europe following the Brustle decision. PMID- 24236920 TI - The patent-regulatory regime in Canada. PMID- 24236921 TI - Big Pharma vs India's Patent Office. PMID- 24236924 TI - Building structure-activity insights through patent mining. AB - One gap in current patent-mining practice is the lack of tools to build SAR knowledge. Here, we report a novel technique that enabled us to derive useful SAR information from the exemplified structures of a series of patents. In our approach, exemplified chemical structures were extracted from patent documents. They were grouped into structural series based on similarity and binding mode, after which the R-group table was generated. By analyzing R-group usages over time, we were able to build insights into SAR of a structural series, even though the biological activities were not available. PMID- 24236925 TI - Learning from practice: compulsory licensing cases and access to medicines. AB - In March 2012, India issued its first compulsory license for a kidney cancer drug. India is one of several countries that have applied the flexibility incorporated in the Agreement on Trade-related Aspects of IP rights. It is expected that the importance of compulsory licenses may grow in the future due to the loss of generic drugs sources after the introduction of pharmaceutical product patents in India, the continuing high prevalence of epidemics, such as of HIV/AIDS, in developing countries and the increase in noncommunicable diseases in these nations. This article analyses the effectiveness and feasibility of compulsory licenses to ameliorate access to medicines based on the historical, factual and legal backgrounds of case examples, such as in Thailand, Canada/Rwanda and India. It addresses challenges and controversial questions, such as the interpretation of the compulsory licensing conditions, the questions surrounding a systematic use of compulsory licenses and the lack of economic incentives for generic pharmaceutical companies' participation to export drugs to countries without manufacturing capacities. Lessons from the cases discussed and implications for policymakers are outlined. PMID- 24236926 TI - Inhalation therapy to treat pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vascular system, which may lead to right-heart failure or early death in the absence of effective treatment. The current therapy for PAH mainly includes phosphodiesterase inhibitors, prostanoids and endothelin receptor antagonists. These, however, have adverse effects when administered via conventional routes. There is a clear and critical need for the development of a novel delivery system that can efficiently deliver the drug to lung vasculature and minimize adverse effects. This article summarizes the inhalation devices and recent patents in the area of inhalable therapy for the treatment of PAH. Various patents are discussed that describe the application of inhalable therapy to target lung vasculature and to reduce dose-related side effects in PAH treatment. Entry of some inhalable delivery approaches into clinical trials is the result of progress in inhalable therapies for the treatment of PAH. PMID- 24236927 TI - Innovative IPV from attenuated Sabin poliovirus or newly designed alternative seed strains. AB - This article gives an overview of the patent literature related to innovative inactivated polio vaccine (i-IPV) based on using Sabin poliovirus strains and newly developed alternative recombinant poliovirus strains. This innovative approach for IPV manufacturing is considered to attribute to the requirement for affordable IPV in the post-polio-eradication era, which is on the horizon. Although IPV is a well-established vaccine, the number of patent applications in this field was seen to have significantly increased in the past decade. Currently, regular IPV appears to be too expensive for universal use. Future affordability may be achieved by using alternative cell lines, alternative virus seed strains, improved and optimized processes, dose sparing, or the use of adjuvants. A relatively short-term option to achieve cost-price reduction is to work on regular IPV, using wild-type poliovirus strains, or on Sabin-IPV, based on using attenuated poliovirus strains. This price reduction can be achieved by introducing efficiency in processing. There are also multiple opportunities to work on dose sparing, for example, by using adjuvants or fractional doses. Renewed interest in this field was clearly reflected in the number and diversity of patent applications. In a later stage, several innovative approaches may become even more attractive, for example the use of recombinant virus strains or even a totally synthetic vaccine. Currently, such work is mainly carried out by research institutes and universities and therefore clinical data are not available. PMID- 24236928 TI - New antibacterial agents: patent applications published in 2010. AB - This review summarizes patent applications from 2010 for small molecules for which there is a claim of antibacterial activity. The primary criterion for inclusion in this analysis was reporting of cellular antibacterial activity data (MICs) for at least one compound. Patent applications are reviewed according to their biological target and antibacterial class. Protein synthesis inhibitors disclosed in this period include inhibitors of the 50S ribosome subunit (oxazolidinones, macrolides/ketolides and pleuromutilins), 30S ribosome subunit (aminoglycosides and tetracyclines) and nonribosomal targets (PDF inhibitors). DNA synthesis inhibitors include inhibitors of GyrA/ParC and GyrB/ParE. Cell envelope disruptors disclosed in 2010 cover both inhibitors of cell-envelope synthesis (LpxC inhibitors, beta-lactams and glycopeptides), as well as membrane disruptors (lipopeptides and polymyxins). Other antibacterial classes covered in this review include rifamycins and antibacterial peptides. Patent applications for compounds aimed at overcoming resistance mechanisms (efflux inhibitors and beta-lactamase inhibitors) are also described. PMID- 24236929 TI - Oncolytic virus therapies. AB - Oncolytic virus (OV) therapy currently represents one of the most promising approaches to cancer treatment for their dual anticancer mechanisms: direct lysis of cancer cells (oncolytic feature) and activation of the immunosystem (cancer vaccine aspect). The latter demonstrates the advantage of a multi-target approach against multiple tumor-associated antigens. Since the 2005 SFDA (the Chinese FDA) approval for the clinical use of OncorineTM, the first human OV-based cancer treatment, more than 200 patents have been filed worldwide and several Phase I/II studies have been conducted. This patent review analyzes patents and clinical studies of the most promising OV products to highlight the pros and cons of this innovative anticancer approach, which is currently being tested in several cancers (i.e., hepatocellular carcinoma, melanoma and glioblastoma) by systemic as well as intratumoral injection. Clinical results, although effective only for a limited period of time, are encouraging. Combined treatments with radio or chemotherapeutic protocols are also in progress. PMID- 24236931 TI - Genetic differentiation of southeast Baltic populations of sea trout inferred from single nucleotide polymorphisms. AB - Sea trout (Salmo trutta m. trutta) is a migratory form of brown trout common in the Baltic Sea. Nine populations from the southeast Baltic (Poland; Lithuania; Denmark, Bornholm; Estonia and Russia) were genotyped using iPLEX Gold technology (Sequenom) with 62 informative SNPs. A diagnostic panel of 23 SNPs was applied to estimate genetic differentiation and assess the population structure of Baltic sea trout. The highest level of pairwise FST differences was observed between the Russian (East Gulf of Finland) and Polish (Baltic main basin) populations. The lowest differences were between the two Polish and the Polish and Lithuanian populations. A genetic similarity was noted between the Estonian Riguldi River and Danish Bornholm populations, and this finding was supported by a Bayesian and factorial correspondence analysis. Diversity within populations was highest for populations from Estonia and lowest for the Lithuanian population. Genetic structure analysis indicated that individuals from the nine populations were clustered into four groups. PMID- 24236932 TI - Evaluation of time course and predicting factors of progression of paroxysmal or persistent atrial fibrillation to permanent atrial fibrillation. AB - BACKGROUND: To evaluate time course and predictors of progression of paroxysmal or persistent atrial fibrillation (AF) to permanent AF. METHODS AND RESULTS: We included 460 patients referred for paroxysmal (n = 337) or persistent (n = 123) AF between 1994 and 2012. Mean follow-up was 13.2 +/- 6.5 years. AF progression rate was 3.7% per year, 19.7% at 5 years, and 38.1% at 10 years. Lone AF was diagnosed in 217 patients (47%). Predictors of permanent AF were: age, persistent AF, left atrial (LA) size, left ventricular-fractional shortening (LV-FS), lack of antiarrhythmic (AA) drugs, VVI pacing (P < 0.001 for all), and valvular disease (P < 0.02). Independent predictors were age (P < 0.001), persistent AF (P < 0.001), LA diameter (P < 0.005), lack of AA drugs (P < 0.005), and VVI pacing (P < 0.01). When adjusted at means of covariates, persistent AF and age >75 years remained highly significant (P < 0.01). LA dimension >50 mm was highly significant at univariate model (P < 0.001) but to a lesser extent when adjusted (P < 0.05). In patients with paroxysmal AF-with age <75 years-on AA drugs, progression rate to permanent AF was 6.5% at 5 years and 23.7% at 10 years. Among four predictors (age, LA size, LV-FS, and VVI pacing), only age (P < 0.01) and LA size (P < 0.005) remained independently significant, but LA size was not significant when adjusted. CONCLUSIONS: Progression to permanent AF is a slow process. Aging, LA size, VVI pacing, lack of AA therapy, and a persistent form of AF independently increased the progression to permanent AF. PMID- 24236933 TI - On the new analytical solution for a well in Cartesian coordinates with MODFLOW comparisons. AB - In this paper, the comparison process of Batu (2012) generalized three dimensional well hydraulics solution for confined aquifers in Cartesian coordinates with MODFLOW is presented. First, a brief description of Batu (2012) solution along with the governing equations and some of its key features are described. The final average drawdown expression in an observation well is given with the conversion expressions from Cartesian to radial coordinates. A generalized comparison using Batu (2012), Hantush (1964), and MODFLOW (Harbaugh et al. 2000), for vertical wells in horizontally isotropic aquifers, that is, ayx = Ky /Kx = 1, is presented. Comparisons are also presented with Batu (2012) and MODFLOW for horizontally anisotropic aquifers, that is, ayx ? 1. After that comparisons are presented for horizontal wells between Batu (2012) and MODFLOW. PMID- 24236934 TI - Food allergy and food-based therapies in neurodevelopmental disorders. AB - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided. PMID- 24236935 TI - Diabetes mellitus: novel insights, analysis and interpretation of pathophysiology and complications management with imidazole-containing peptidomimetic antioxidants. AB - Patients suffering from the severe complications associated with both insulin- (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM): nephropathy, retinopathy, neuropathy, and atherosclerosis are still largely left without a prospect of an efficient treatment. Chronic hyperglycaemia, the primary clinical manifestation of diabetes, is associated with development of certain of the diabetic complications. The accelerated formation of advanced glycation end products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. Glucose and alpha-dicarbonyl compounds chemically attach to proteins and nucleic acids without the aid of enzymes. Initially, chemically reversible Schiff base and Amadori product adducts form in proportion to glucose concentration. The major biological effects of excessive nonenzymatic glycosylation are leading to increased free radical production and compromised free radical inhibitory and scavenger systems, inactivation of enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated proteins and trapping of soluble proteins by glycosylated extracellular matrix (both may progress in the absence of glucose); decreased susceptibility to proteolysis; abnormalities of nucleic acid function; altered macromolecular recognition and endocytosis; and increased immunogenicity. The discovery of chemical agents that can inhibit deleterious glycation reactions is potentially of great therapeutic benefit to all diabetes-associated pathologies. This study demonstrates the progress in development of patented carnosine mimetics resistant in formulations to enzymatic hydrolysis with human carnosinases that are acting as a universal form of antioxidant, deglycating and transglycating agents that inhibit sugar mediated protein cross-linking, chelate or inactivate a number of transition metal ions (including ferrous and copper ions), possess lipid peroxidase type of activity and protection of antioxidant enzymes from inactivation (such as in a case of superoxide dismutase). Carnosine biological mimetics react with methylglyoxal and they are described in this study as a glyoxalase mimetics. The imidazole-containing carnosine biological mimetics can react with a number of deleterious aldehydic products of lipid peroxidation and thereby suppress their toxicity. Carnosine and carcinine can also react with glycated proteins and inhibit advanced glycation end product formation. These studies indicate a therapeutic role for imidazole-containing antioxidants (non-hydrolized carnosine, carcinine, D-carnosine, ophthalmic prodrug N-acetylcarnosine, leucyl histidylhidrazide and patented formulations thereof) in therapeutic management strategies for Type 2 Diabetes. PMID- 24236936 TI - Factor structure of the Halstead-Reitan Neuropsychological Battery for children: a brief report supplement. AB - The Halstead-Reitan Neuropsychological Battery (HRNB) is the first factor analyzed neuropsychological battery and consists of three batteries for young children, older children, and adults. Halstead's original factor analysis extracted four factors from the adult version of the battery, which were the basis for his theory of biological intelligence. These factors were called Central Integrative Field, Abstraction, Power, and Directional. Since this original analysis, Reitan's additions to the battery, and the development of the child versions of the test, this factor-analytic research continued. An introduction and the adult literature are reviewed in Ross, Allen, and Goldstein ( in press ). In this supplemental article, factor-analytic studies of the HRNB with children are reviewed. It is concluded that factor analysis of the HRNB or Reitan-Indiana Neuropsychological Battery with children does not replicate the extensiveness of the adult literature, although there is some evidence that when the traditional battery for older children is used, the factor structure is similar to what is found in adult studies. Reitan's changes to the battery appear to have added factors including language and sensory-perceptual factors. When other tests and scoring methods are used in addition to the core battery, differing solutions are produced. PMID- 24236937 TI - An analysis of select emerging executive skills in perinatally HIV-1-infected children. AB - This study examined the effect of perinatal HIV-1 infection on emerging executive skills in children (n = 161) ages 8 to 12 years. HIV-positive (n = 76) and HIV negative (n = 85) children were eligible to participate. The HIV-positive children included those who had experienced a CDC Class C event (greater severity, n = 22) and those who were HIV-positive but who had not experienced a CDC Class C event (less severity, n = 54). Measures of emerging executive functions completed by the children included subtests from the Developmental Neuropsychological Assessment (NEPSY), the Trail-Making Test-Part B, and a subtest from the Woodcock-Johnson Battery-Revised. Ratings of executive functions were obtained from caretakers using the Behavior Rating Inventory of Executive Functions. Generalized estimating equations methods, discriminate analyses, and global deficit score analyses were performed to determine whether differences emerged between the three clinical groups while using strict controls. The present results revealed significant group differences in unadjusted mean scores measuring executive functioning. However, such differences did not remain statistically significant when moderating variables were taken into consideration in the models. The apparent deficit in executive functioning for the HIV-positive children was found to be largely due to differential psychosocial and environmental factors rather than HIV disease and its severity, and in this cohort, the effects of HIV-1 infection on emerging executive functions appeared to be negligible when controlling for treatment and moderating psychosocial variables. PMID- 24236938 TI - Performance and specificity rates in the Test of Memory Malingering: an investigation into pediatric clinical populations. AB - Symptom validity tests are becoming standard as an effort measure during pediatric neuropsychological assessment. An important component of symptom validity test use is understanding limitations of these measures and how select clinical groups may have difficulty with them. Research has begun to clarify the limits of the Test of Memory Malingering (TOMM) with diverse childhood diagnoses. This study compared TOMM scores of children (N = 86) classified with common childhood disorders. Findings suggest that a substantial proportion of children performed below the recommended cutoff score of 45 on Trial 2 and attained varied specificity rates. This included children with conduct disorders (85%), affective disorders (92%), traumatic brain injury (83%), attention-deficit hyperactivity disorder (93%), learning disabilities (100%), and pervasive developmental disorder (88%). The group with the most children scoring below the cutoff was children with intellectual disabilities (76%). This finding is consistent with some of the adult research suggesting that very limited cognitive ability may compromise TOMM performance. Caution may be necessary when drawing conclusions about test-taking effort based on the recommended TOMM cutoff scores when evaluating children with disabilities. PMID- 24236939 TI - The influence of effort on neuropsychological performance in children: is performance on the TOMM indicative of neuropsychological ability? AB - The Test of Memory Malingering (TOMM) is a measure of effort that has traditionally been utilized with adults but is being increasingly used with children, though it is not yet entirely clear what suboptimal TOMM performance means in terms of neuropsychological test scores. The purpose of this study was to investigate whether performance on the TOMM can be used as a predictive marker for neuropsychological performance in children. Participants (N = 75) completed the TOMM, Wechsler Intelligence Scale for Children-Fourth Edition, Wisconsin Card Sorting Test (WCST), Children's Memory Test, and Delis-Kaplan Executive Function System Trails. Results revealed significant correlations between age, education level, IQ, and many of the neuropsychological measures administered, indicating that as children's TOMM scores increase, so do their cognitive performances. Children were subsequently divided into two groups: optimal effort and suboptimal effort, based on their TOMM Trial 2 scores. Results suggest significant differences in IQ performance and WCST Failure to Maintain Set; however, there were no differences in regard to any other neuropsychological measures administered. It was also found that a larger proportion of the younger children (aged 6 to 10 years old) scored below the TOMM cutoff compared with older children. This study illustrates that although correlations exist, suboptimal effort on the TOMM may not predict poorer performance on a neuropsychological evaluation in children as has been reported in other studies. PMID- 24236940 TI - Risky decision making in smoking and nonsmoking college students: examination of Iowa Gambling Task performance by deck type selections. AB - The Iowa Gambling Task (IGT) is used to assess risky decision making in clinical and nonclinical populations. Recent studies have begun to assess performance on the IGT not by number of advantageous and disadvantageous selections, but rather by the pattern of performance on each of the four individual decks (A, B, C, and D). The present study sought to further examine deck selection patterns among smoking and nonsmoking college students, as mixed results have been found on the IGT in nicotine and as a function of substance satiation level. Participants were 136 undergraduates (48 male; mean age 19.24 years), of whom 70 were nonsmokers. Thirty-one smokers abstained from smoking overnight. Performance on the IGT was broken into two blocks (Trials 1-40, Trials 41-100) for each of the four decks. Abstinent smokers selected more from Deck A on Block 2 than the ad libitum smokers. No group or block differences were found for Decks B or C. Selections from Deck D increased as the task progressed, regardless of smoking status. Ad libitum smokers preferred Deck B to Deck A on Block 2. The results provide some evidence that nicotine satiation level affects IGT deck selections among smokers. PMID- 24236941 TI - The value of embedded measures in detecting suboptimal effort in children: an investigation into the WISC-IV Digit Span and CMS Verbal Memory subtests. AB - The Test of Memory Malingering (TOMM) is a measure of test-taking effort that has traditionally been utilized with adults but more recently has demonstrated utility with children. The purpose of this study was to investigate whether commonly used neuropsychological measures can be used as embedded measures in detecting effort during testing. Participants (N = 75) who completed neuropsychological evaluations including the TOMM, Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) Digit Span, Children's Memory Scale (CMS) Verbal Memory, and other neuropsychological measures were divided into two groups: Optimal Effort and Suboptimal Effort, based on their TOMM Trial 2 scores. Digit Span findings suggest a useful standard score of <= 70 resulted in optimal cutoff scores, yielding specificity of 94% and sensitivity of 44%. The CMS Verbal Memory Recall > Recognition scores did not appear as valuable indicating a discrepancy of 20+ points were required for specificity to attain optimal scores of 90% and sensitivity of 11%. This study illustrates the WISC-IV may have good utility in determining optimal effort; however, the CMS may not be as functional. PMID- 24236942 TI - Are fine-motor impairments a defining feature of nonverbal learning disabilities in children? AB - The most commonly used model of nonverbal learning disabilities (NVLD) is the Rourke model. This model includes bilateral deficits in psychomotor skills as a primary neuropsychological deficit. Extant studies have identified attentional issues as one of the components seen in many children with NVLD. Forty-five children divided into three groups completed a battery of tests including psychomotor skills. Groups were defined as children with NVLD, children with attention-deficit hyperactivity disorder-Predominantly Inattentive type, and typically developing children. No significant differences were found among the groups on measures of motor speed. Furthermore, the means were not in the expected direction, as children with NVLD actually performed faster than typically developing children. This finding suggests that measures of motor speed should not be solely used to identify children with NVLD and that more research is needed to clearly identify appropriate diagnostic criteria. PMID- 24236943 TI - Does size matter? An investigation into the Rey Complex Figure in a pediatric clinical sample. AB - The Rey Complex Figure Test (RCF) copy requires visuoconstructional skills and significant attentional, organizational, and problem-solving skills. Most scoring schemes codify a subset of the details involved in figure construction. Research is unclear regarding the meaning of figure size. The research hypothesis of our inquiry is that size of the RCF copy will have neuropsychological significance. Data from 95 children (43 girls, 52 boys; ages 6-18 years) with behavioral and academic issues revealed that larger figure drawings were associated with higher RCF total scores and significantly higher scores across many neuropsychological tests including the Wechsler Individual Achievement Test-Second Edition (WIAT-II) Word Reading (F = 5.448, p = .022), WIAT-II Math Reasoning (F = 6.365, p = .013), Children's Memory Scale Visual Delay (F = 4.015, p = .048), Trail-Making Test Part A (F = 5.448, p = .022), and RCF Recognition (F = 4.862, p = .030). Results indicated that wider figures were associated with higher cognitive functioning, which may be part of an adaptive strategy in helping facilitate accurate and relative proportions of the complex details presented in the RCF. Overall, this study initiates the investigation of the RCF size and the relationship between size and a child's neuropsychological profile. PMID- 24236944 TI - The importance of assessing for abuse and neglect in children with chronic health conditions referred for neuropsychological evaluation. AB - Chronic childhood illnesses have been demonstrated to negatively impact family functioning by introducing new or additive stress on all members of the family system, as well as by increasing financial burden and social isolation. Although these factors have not necessarily been shown to have a direct causal effect on increased rates of abuse in children with chronic illnesses, these children have nonetheless been demonstrated to be at greater risk for neglect and physical and sexual abuse. Children with chronic health care needs are increasingly likely to be referred for neuropsychological evaluation. Thorough assessment of maltreatment would be a valuable addition to all neuropsychological evaluations of children presenting with chronic health conditions. PMID- 24236945 TI - Neuropsychological profiles and subsequent diagnoses of children with early life insults: do caregiver reports suggest deficits? AB - Many types of early life events can cause cerebral dysfunction; however, not all children have medical records or neurologic imaging documenting brain injuries. Rather, many neuropsychologists base their findings on caregiver reports describing possible early brain insults. Neuropsychological studies suggest that brief perinatal cyanosis and/or childhood neglect may negatively affect cognitive functioning. Should the mere suggestion of these events from caregiver reports be enough to suggest deficits? This study examines four groups of children: those with (1) reported nuchal cord compression with brief cyanosis, (2) reported childhood neglect, (3) reported history of both, and (4) reported history of none. It was hypothesized that based on the literature of these populations, children who present at an evaluation with the report of these insults would also present cognitive deficits. Results revealed no significant difference in intellect, memory, or academic abilities. A significant difference was shown between groups during the Wisconsin Card-Sorting Test Failure to Maintain Set, as groups with a history of neglect had lower scores. A history of childhood neglect also suggested an increased risk for subsequent emotional/behavioral diagnoses. These findings suggest that although the profiles range between low-average and average, reports of early life insults can flag potential deficits in a child's neuropsychological profile. PMID- 24236946 TI - Triheptanoin partially restores levels of tricarboxylic acid cycle intermediates in the mouse pilocarpine model of epilepsy. AB - Triheptanoin, the triglyceride of heptanoate, is anticonvulsant in various epilepsy models. It is thought to improve energy metabolism in the epileptic brain by re-filling the tricarboxylic acid (TCA) cycle with C4-intermediates (anaplerosis). Here, we injected mice with [1,2-(13) C]glucose 3.5-4 weeks after pilocarpine-induced status epilepticus (SE) fed either a control or triheptanoin diet. Amounts of metabolites and incorporations of (13) C were determined in extracts of cerebral cortices and hippocampal formation and enzyme activity and mRNA expression were quantified. The percentage enrichment with two (13) C atoms in malate, citrate, succinate, and GABA was reduced in hippocampal formation of control-fed SE compared with control mice. Except for succinate, these reductions were not found in triheptanoin-fed SE mice, indicating that triheptanoin prevented a decrease of TCA cycle capacity. Compared to those on control diet, triheptanoin-fed SE mice showed few changes in most other metabolite levels and their (13) C labeling. Reduced pyruvate carboxylase mRNA and enzyme activity in forebrains and decreased [2,3-(13) C]aspartate amounts in cortex suggest a pyruvate carboxylation independent source of C-4 TCA cycle intermediates. Most likely anaplerosis was kept unchanged by carboxylation of propionyl-CoA derived from heptanoate. Further studies are proposed to fully understand triheptanoin's effects on neuroglial metabolism and interaction. PMID- 24236948 TI - Low level of inflammatory marker in hyperhomocysteinemic patients on statin therapy. AB - Inflammatory processes including increased activation of chemokines play an important role in atherogenesis. Patients with hyperhomocysteinemia have increased risk for cardiovascular events that potentially involve enhanced inflammation. Statins may have anti-inflammatory actions at least partly independent on their lipid-lowering effects. In the present study we examined the association between statins and chemokine levels in patients with hyperhomocysteinemia. Our major findings were (i) patients with hyperhomocysteinemia on statin treatment (n = 14) have significantly lower plasma levels of the CXC chemokine epithelial neutrophil activating peptide (ENA)-78 compared to hyperhomocysteinemic patients not on statin treatment (n = 8). In fact, levels of ENA-78 in statin-treated patients did not differ from those of healthy controls (n = 17); (ii) plasma levels of ENA-78 and growth-related oncogene (GRO)alpha correlated with levels of LDL-cholesterol and homocysteine; (iii) in contrast, plasma levels of the CC chemokine monocyte chemoattractant peptide (MCP)-1 were similar between statin-users, non-statin users and controls, and did not correlate with levels of LDL-cholesterol or homocysteine; and (iv) in vitro studies showed that simvastatin significantly reduced release of ENA-78, GROalpha and MCP-1 from peripheral blood mononuclear cells in healthy controls (n = 7) in a concentration-dependent manner, without affecting release of RANTES. Our data may suggest that ENA-78 and GROalpha may be involved in the inflammatory arm of atherogenesis in patients with elevated risk of cardiovascular disease, with potential down-regulatory effect of statins. PMID- 24236949 TI - Who writes, whose rights, and who's right? Issues in authorship. PMID- 24236950 TI - Retention, burnout and the future of nursing. PMID- 24236947 TI - GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801 induced impairment in prepulse inhibition and working memory in Y-maze test in mice. AB - BACKGROUND AND PURPOSE: Despite ample evidence supporting the N-methyl-D aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co-agonists (D-serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub-types differ in their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA receptors (Mullasseril et al.). EXPERIMENTAL APPROACH: The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment in working memory in Y-maze spontaneous alternation test. KEY RESULTS: We found that systemic administration of CIQ (20 mg.kg-1, i.p.) in mice reversed MK-801 (0.15 mg.kg-1, i.p.)-induced, but not methamphetamine (3 mg.kg-1, i.p.)-induced, deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- and methamphetamine-induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK-801-induced working memory deficit in spontaneous alternation in a Y-maze. CONCLUSION AND IMPLICATIONS: Together, these results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia. PMID- 24236952 TI - A neuropsychological investigation of the Delis-Kaplan Executive Function System. AB - Despite a strong historical association between frontal lobe lesions and executive dysfunction, questions remain regarding the neuropsychological characterization of specific regions within the prefrontal cortex, as well as the utility of some executive function measures. The Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001) has gained popularity as a collection of executive function tests, but its sensitivity and specificity for detecting focal frontal lobe dysfunction remain uncertain. The current study investigated performances of patients with focal ventromedial prefrontal cortex (vmPFC, n = 13), dorsolateral prefrontal cortex (dlPFC, n = 14), and nonfrontal (NF, n = 18) lesions on the entire D-KEFS battery. We also obtained IQ data from conventional measures (the Wechsler Adult Intelligence Scale-Third Edition and Fourth Edition, WAIS-III/IV). On six D-KEFS indices, patients with dlPFC lesions performed lower than patients with vmPFC and NF lesions. On three other indices, the performances of the dlPFC group were lower than those of the NF group, but did not differ from those of the vmPFC group. However, none of these between group differences were statistically significant after full-scale IQ and processing speed were controlled for, suggesting that the observed weaknesses in patients with dlPFC lesions were not specific to executive functions. Patients with vmPFC and NF lesions could not be differentiated based on their performances on any D-KEFS measures. While some D-KEFS measures show promise in differentiating patients with dlPFC lesions, the clinical advantage of using the D-KEFS over more traditional measures is not empirically compelling. PMID- 24236953 TI - Childlessness in Nigeria: perceptions and acceptability. AB - Childlessness has major psychological and social implications for affected persons, especially in settings where fertility is highly valued. While a number of studies have documented how childlessness is perceived in these societies and the multitude of adverse consequences suffered by affected individuals, studies have not made a clear distinction between voluntary and involuntary childlessness in these settings. Using focus-group discussions from three Nigerian communities, this study explores societal perception and acceptance of childlessness in Nigeria, focusing on both voluntary and involuntary childlessness. Findings show that not having children, whether voluntarily or not, contributes to a kind of invisibility and poverty in Nigeria. Regardless of the reason, voluntary childlessness evoked strong negative feelings among discussants. The study also shows the broad definition given to voluntary childlessness in Nigeria as including individuals that are childless because they chose to stay with an infertile partner and also those who could not have biological children and chose not to adopt. Childlessness is not yet embraced in Nigeria, where pronatalist culture is still very strong. However, the study noted a more tolerant attitude to involuntary childlessness, suggesting possible changes in perceptions of the condition. Policy and programme implications of the findings are discussed. PMID- 24236954 TI - Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo. AB - Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-beta-hydroxylase-expressing neurons in mice [DbetaH(Cre/0) ;VGLUT2(flox/flox) mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (DbetaH(Cre/0) ), using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2 mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM CA neurons had similar morphology and axonal projections in DbetaH(Cre/0) and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in DbetaH(Cre/0) and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in DbetaH(Cre/0) mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DbetaH(Cre/0) mice only. Vagal responses were unaffected by alpha1 -adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate. PMID- 24236956 TI - Consensus paper of the WFSBP task force on biological markers: biological markers for alcoholism. AB - OBJECTIVES: This article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated. METHODS: In this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field. RESULTS: More recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies. CONCLUSIONS: In addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results. PMID- 24236957 TI - Transmission mode desorption electrospray ionization (TM-DESI) for simultaneous analysis of potential inorganic and organic components of radiological dispersion devices (RDDs). AB - Transmission mode desorption electrospray ionization (TM-DESI) coupled to an ion trap mass spectrometer capable of source collision-induced dissociation (CID) was used to completely analyze radiological dispersion device components. Source CID significantly enhanced the signal for metal ions by reducing adducts while eliminating chemical noise from background molecules through extensive fragmentation. Source CID spectra yielded reasonably accurate isotopic ratios for the metals studied. By switching the source CID on and off between scans, all major constituents in mixtures of simulated radionuclides and explosives were simultaneously observed. These results indicate that TM-DESI/ion trap technology could be a powerful on-site tool for nuclear forensics. PMID- 24236959 TI - Botulinum toxin injection and phenol nerve block for reduction of end-of-life pain. AB - BACKGROUND: Injectable antispasticity agents have been utilized for the reduction of pain. However, there are no reports of its use for end-of-life pain. PATIENT CASE: A 62-year-old female with a history of progressive left frontotemporal glioblastoma status post gross total resection, radiation, and chemotherapy presented to the physical medicine and rehabilitation (PM&R) clinic for management of spastic quadriplegia and pain. At the time of presentation to the PM&R clinic she was no longer eligible for further cancer treatment. The patient had been declining neurologically with cognitive changes, weakness, and increasing spasticity. The patient had an Edmonton Symptom Assessment Scale (ESAS) pain score of 8/10 at her visit, as reported by her husband. She exhibited mild to moderate spasticity during the exam. Cognitively, she was unable to follow commands and would fluctuate between being awake for a few minutes and sleeping during the exam. She was not on any oral muscle relaxants and none were started due to her state of hypoarousal. Nine days after the initial consultation she received 700 units of onabotulinum toxin into her bilateral upper limbs and left thigh and a phenol nerve block to her left tibial nerve. At a follow-up visit 28 days later in the palliative care clinic, the ESAS pain score was 0. The patient died 51 days post-injection. CONCLUSION: The case report demonstrates the use of injectable antispasticity agents in the reduction of end-of-life pain in a glioblastoma patient. PMID- 24236958 TI - The impact on the family carer of motor neurone disease and intervention with noninvasive ventilation. AB - BACKGROUND: The diagnosis of motor neurone disease (MND) has a profound effect on the functioning and well-being of both the patient and their family, with studies describing an increase in carer burden and depression as the disease progresses. AIM: This study aimed to assess whether patient use of noninvasive ventilation (NIV) impacted on their family carer, and to explore other sources of carer burden. DESIGN: The study used qualitative interviews and scaled measures of carer health and well-being completed at three monthly intervals until patient end of life. PARTICIPANTS: Sixteen family carers were followed up over a period ranging from one month to two years. RESULTS: NIV was perceived as having little impact on carer burden. The data however highlighted a range of sources of other burdens relating to the physical strain of caring. The Medical Outcomes Study Short Form (SF-36 Health Survey) Physical Component Summary (PCS) scores were considerably below that of the Mental Component Summary (MCS) score at baseline and at all following time points. Carers described the physical effort associated with patient care and role change; the challenge inherent in having time away; and problems relating to the timing of equipment and service delivery. CONCLUSIONS: NIV can be recommended to patients without concerns regarding increasing carer burden. The predominant source of burden described related to the physical impact of caring for a patient with MND. Services face challenges if this physical burden is to be reduced by providing equipment at an optimal time and successfully coordinating their input. PMID- 24236960 TI - Ischemic postconditioning in human DCD kidney transplantation is feasible and appears safe. AB - Ischemic postconditioning may improve outcome after kidney transplantation. We performed a pilot study to assess feasibility and safety of ischemic postconditioning in human donation-after-circulatory-death kidney transplantation. Twenty patients were included. Primary outcome was rate of serious adverse events. Secondary outcomes were incidence of DGF and renal function at 3 months. Data were compared to a historical control group (n = 40). Furthermore, we performed a paired kidney analysis using the contralateral kidney (n = 11). Donor age and serum creatinine were higher in the experimental group compared with historical control: 57.7 (20-71) vs. 51.5 (24-74) years (P = 0.01) and 79 (40-156) MUmol/l vs. 64 (25-115) MUmol/l (P = 0.047). Postconditioning could be applied all times. One complication, a venous tear, occurred related to postconditioning. The experimental group experienced more DGF (85% vs. 63%) (P = 0.07). Serum creatinine at month 3 was 166 (109-331) MUmol/l vs. 159 (81-279) MUmol/l (P = 0.71). Paired kidney analysis showed no significant differences in DGF (72.2% vs. 54.5%, P = 0.66) and serum creatinine 199 (90-473) MUmol/l vs. 184 (117-368) MUmol/l (P = 0.76). This is the first report of applying IPoC in human kidney transplantation. Although IPoC is feasible and appears to be safe, no benefit in terms of reduced DGF or better renal function was observed (Dutch trial registry number NTR 3117). PMID- 24236961 TI - A cross-sectional study of glycaemic control, complications and psychosocial functioning among 18- to 35-year-old adults with type 1 diabetes. AB - AIMS: To describe the level of glycaemic control, complications and psychosocial functioning and the relationships between these variables in the under-researched group of younger adults with type 1 diabetes. METHODS: Local electronic health records provided data on age, gender, disease duration, HbA1c and complications for 710 younger adults (18-35 years) with type 1 diabetes. A questionnaire with wide-ranging psychometric scales was used to measure various aspects of psychosocial functioning: the burden of diabetes-related problems, well-being, self-esteem, perceived competence in managing diabetes, perceived autonomy support from health professionals and self-management motivations. Furthermore, patients reported weekly self-monitored blood glucose measurements and insulin administration. Associations between HbA1c , complication and psychosocial indicators were tested using linear and logistic regression models, adjusted stepwise for confounders, including age, gender, diabetes duration, continuous subcutaneous insulin infusion, smoking and BMI. RESULTS: In total, 406 (57%) participants responded. The responders had a mean age of 27.1 (5.1) years, a mean diabetes duration of 13.5 (7.9) years and an HbA1c of 66 mmol/mol (8.2%), with similar values for both genders (P = 0.87). Complications were observed among women more commonly than among men (31.6 vs. 18.8%, P < 0.01), and high distress levels were more prevalent among women compared with men (51.2 vs. 31.9%, P < 0.0001). Except for perceived autonomy support, the psychosocial variables were all associated with HbA1c (P < 0.001). CONCLUSIONS: The high prevalence of poor glycaemic control, early complications and psychosocial distress require health promoting interventions tailored to the interrelated clinical and psychosocial needs of younger adults with type 1 diabetes. PMID- 24236962 TI - US patent law and the attorney-client privilege. PMID- 24236963 TI - Why pharmaceutical scientists need to keep an eye on Bowman v. Monsanto. PMID- 24236964 TI - Roche v. Cipla litigation. PMID- 24236968 TI - Biosimilars: impact of differences with Hatch-Waxman. AB - A comparison of the Hatch-Waxman Act for approval of small-molecule pharmaceuticals with the Biological Price Competition and Innovation Act for approval of biosimilars provides insight into the market entry and patent litigation for biosimilars. Key differences between the two statutes include a longer period of statutory exclusivity for biosimilars, no 30-month stay for a reference product sponsor upon initiation of litigation, and no 180-day market exclusivity period for the first filer of an application for approval of a biosimilar in the absence of interchangeability. These differences will focus the incentive to settle any patent litigation on the risk of invalidity and/or noninfringement of the reference product sponsor's patents. A biosimilar applicant should develop the best case for invalidity and/or noninfringement of these patents, identify third-party patents and develop a freedom to operate strategy, and file for patents on production, formulation, or use of the biosimilar. PMID- 24236969 TI - Ontology-based content analysis of US patent applications from 2001-2010. AB - Ontology-based semantic text analysis methods allow to automatically extract knowledge relationships and data from text documents. In this review, we have applied these technologies for the systematic analysis of pharmaceutical patents. Hierarchical concepts from the knowledge domains of chemical compounds, diseases and proteins were used to annotate full-text US patent applications that deal with pharmacological activities of chemical compounds and filed in the years 2001 2010. Compounds claimed in these applications have been classified into their respective compound classes to review the distribution of scaffold types or general compound classes such as natural products in a time-dependent manner. Similarly, the target proteins and claimed utility of the compounds have been classified and the most relevant were extracted. The method presented allows the discovery of the main areas of innovation as well as emerging fields of patenting activities - providing a broad statistical basis for competitor analysis and decision-making efforts. PMID- 24236970 TI - Towards the ophthalmology patentome: a comprehensive patent database of ocular drugs and biomarkers. AB - We are currently building a database of all patent documents that contain substantial information related to pharmacology, drug delivery, tissue technology, and molecular diagnostics in ophthalmology. The goal is to establish a 'patentome', a body of cleaned and annotated data where all text-based, chemistry and pharmacology information can be accessed and mined in its context. We provide metrics on patent convention treaty documents, which demonstrate that ocular-related patenting has shown stronger growth than general patent cooperation treaty patenting during the past 25 years, and, while the majority of applications of this type have always provided substantial biological data, both data support and objections by patent examiners have been increasing since 2006 2007. Separately, we present a case study of chemistry information extraction from patents published during the 1950s and 1970s, which reveal compounds with corneal anesthesia potential that were never published in the peer-reviewed literature. PMID- 24236971 TI - Patent term extension in Japan: challenges still lay ahead even after the 2011 revision. AB - Japan has a patent term extension (PTE) system similar to supplemental protection certificates in Europe and PTEs in the USA; however, the Japanese PTE system is different in many aspects. It is relatively known that it is not so difficult to obtain multiple PTEs, but as a matter of fact it can be challenging. Recently, the Supreme Court of Japan issued important decisions relating to multiple PTEs, followed by revision to the Japan Patent Office's Examination Guidelines. Further, calculation of an extended term is also an issue in obtaining a PTE in Japan, which is different from those of European supplemental protection certificates or US PTE systems. The Japanese court also held an important decision in this regard, particularly, how clinical trial outside Japan may be considered in the calculation of extended patent right. Additional recent court decisions issued in terms of PTE matter are introduced. PMID- 24236972 TI - SGLT inhibitors: a novel target for diabetes. AB - Inhibiting sodium-glucose co-transporters (SGLT1/SGLT2), which have a key role in the absorption of glucose in the kidney and/or GI tract has been proposed as a novel therapeutic strategy for diabetes. Thus, screening and patenting of chemical compounds for SGLT1/SGLT2 gets more importance in the development of new drugs in diabetes. Several companies are developing SGLT inhibitors, some of which are now in various stages of clinical development. Some molecules in the pipeline, including dapagliflozin, canagliflozin, ASP1941, BI10773, LX4211, RG7201 and TS071, are at various stages of drug development. This patent review presents the overall progress carried out in the development of SGLT inhibitors over the last decade with the active participation of various pharmaceutical companies. This class of drug is anticipated to have a large impact on diabetes field and predicting to attain a blockbuster status. PMID- 24236973 TI - Metabotropic glutamate receptor 5-positive allosteric modulators for the treatment of schizophrenia (2004-2012). AB - The mGlu5, a class C G-protein-coupled receptor and member of the group I mGlu receptor family, has been demonstrated to play a role in a number of therapeutic areas within the CNS, including schizophrenia, dementia, epilepsy, cognition, drug abuse, and fragile X syndrome. Small-molecule modulation of mGlu5 via positive allosteric modulators (PAMs) is being pursued as a promising approach for the treatment of schizophrenia and has been validated preclinically in a number of animal models. This article provides a brief historical overview of mGlu5 PAMs in the primary literature followed by a comprehensive overview of the patent literature since 2004. Schizophrenia is a complex disorder and although no mGlu5 PAMs have progressed into clinical trials in patients, the target continues to show promise as an attractive non-dopaminergic therapy. The successful development of mGlu5 PAMs for clinical testing must address several issues, including challenges associated with 'molecular switches', allosteric-agonist activity and stimulus bias. PMID- 24236974 TI - Pharmacological chaperones for enzyme enhancement therapy in genetic diseases. AB - Pharmacological chaperone therapy (PCT) is a rather new approach consisting in targeting incorrectly folded proteins by small molecules, thus, facilitating the correct folding of the protein and inducing a recovery of its functionality. Many diseases result from mutations on specific genes; this patent review focuses on those pathologies where PCT has a potential application for enzymatic enhancement. Rare diseases are the main area where PCT has been applied and the most advanced compounds are aiming to cure lysosomal storage disorders such as Fabry, Pompe or Gaucher. Until now, most compounds used as pharmacological chaperones were based on substrate-like chemical structures but recently new nonsubstrate-like and non-inhibitory compounds have been disclosed for Gaucher and Pompe diseases. This initiates a new era for pharmacological chaperones with more diverse chemical structures and binding modes. This review covers the patents relating to enzyme enhancement on pharmacological chaperone therapy. Only an update is presented for Gaucher disease, where PCT is highly applied and recently reviewed. PMID- 24236975 TI - The oral delivery of peptides and proteins: established versus recently patented approaches. AB - Over the past 30 years there has been significant research into technologies that promote the delivery of high molecular weight, poor membrane-permeable compounds across the gut. Most work has concentrated on the delivery of peptides and proteins. However, technologies have also been applied to compounds such as poorly membrane-permeable small molecules, heparin and oligonucleotides. Much of this research has been characterized by early promise with many systems showing positive results in animal studies. Success in man has proven more elusive. In 2011, however, the oral delivery of peptides took one step closer to commercial reality when Tarsa Therapeutics announced that it had achieved positive Phase III data for oral recombinant salmon calcitonin. This article reviews the current development status of oral delivery systems for peptides and proteins and examines recent patent activity in this field based mainly on US patents issued in the last 2-3 years. PMID- 24236978 TI - Facile synthesis of hierarchical networks composed of highly interconnected V2O5 nanosheets assembled on carbon nanotubes and their superior lithium storage properties. AB - Hierarchical networks with highly interconnected V2O5 nanosheets (NSs) anchored on skeletons of carbon nanotubes (CNTs) are prepared by a facile hydrothermal treatment and a following calcination for the first time. Benefiting from these unique structural features, the as-prepared CNT@V2O5 material shows dramatically excellent electrochemical performance with remarkable long cyclability (137-116 mA h g(-1) after 400 cycles) at various high rates (20 C to 30 C) and very good rate capability for highly reversible lithium storage. The excellent electrochemical performance suggests its promising use as a cathode material for future lithium-ion batteries. PMID- 24236977 TI - Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol. AB - Dopamine (DA) plays an important role in integrative functions contributing to adaptive behaviors. In support of this essential function, DA modulates synaptic plasticity in different brain areas, including the striatum. Many drugs used for cognitive enhancement are psychostimulants, such as methylphenidate (MPH), which enhance DA levels. MPH treatment is of interest during adolescence, a period of enhanced neurodevelopment during which the DA system is in a state of flux. Recent epidemiological studies report the co-abuse of MPH and ethanol in adolescents and young adults. Although repeated MPH treatment produces enduring changes that affect subsequent behavioral responses to other psychostimulants, few studies have investigated the interactions between MPH and ethanol. Here we addressed whether chronic therapeutic exposure to MPH during adolescence predisposed mice to an altered response to ethanol and whether this was accompanied by altered DA release and striatal plasticity. C57BL/6J mice were administered MPH (3-6 mg/kg/day) via the drinking water between post-natal days 30 and 60. Voltammetry experiments showed that sufficient brain MPH concentrations were achieved during adolescence in mice to increase the DA clearance in adulthood. The treatment also increased long-term depression and reduced the effects of ethanol on striatal synaptic responses. Although the injection of 0.4 or 2 g/kg ethanol dose-dependently decreased locomotion in control mice, only the higher dose decreased locomotion in MPH-treated mice. These results suggested that the administration of MPH during development promoted long-term effects on synaptic plasticity in forebrain regions targeted by DA. These changes in plasticity might, in turn, underlie alterations in behaviors controlled by these brain regions into adulthood. PMID- 24236979 TI - Natural products for Alzheimer's disease therapy: basic and application. PMID- 24236980 TI - Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment. AB - OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds. KEY FINDINGS: Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-alpha-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors. SUMMARY: Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs. PMID- 24236981 TI - Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease. AB - OBJECTIVES: The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is currently the main pharmacological strategy available for Alzheimer's disease (AD). In this sense, many alkaloids isolated from natural sources, such as physostigmine, have been long recognized as acetyl- and butyrylcholinesterase (BChE) inhibitors. Since the approval of galantamine for the treatment of AD patients, the search for new anticholinesterase alkaloids has escalated, leading to promising candidates such as huperzine A. This review aims to summarize recent advances in current knowledge on alkaloids as AChE and BChE inhibitors, highlighting structure-activity relationship (SAR) and docking studies. KEY FINDINGS: Natural alkaloids belonging to the steroidal/triterpenoidal, quinolizidine, isoquinoline and indole classes, mainly distributed within Buxaceae, Amaryllidaceae and Lycopodiaceae, are considered important sources of alkaloids with anti-enzymatic properties. Investigations into the possible SARs for some active compounds are based on molecular modelling studies, predicting the mode of interaction of the molecules with amino acid residues in the active site of the enzymes. Following this view, an increasing interest in achieving more potent and effective analogues makes alkaloids good chemical templates for the development of new cholinesterase inhibitors. SUMMARY: The anticholinesterase activity of alkaloids, together with their structural diversity and physicochemical properties, makes them good candidate agents for the treatment of AD. PMID- 24236982 TI - Berberis aetnensis and B. libanotica: a comparative study on the chemical composition, inhibitory effect on key enzymes linked to Alzheimer's disease and antioxidant activity. AB - OBJECTIVES: This study involves for the first time the evaluation of Berberis aetnensis C. Presl. and Berberis libanotica Ehrenb. ex C.K. Schneid. roots for anticholinesterase and antioxidant properties, with the aim to search compounds possibly useful for the treatment of Alzheimer's disease (AD). METHODS: Samples were evaluated for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The antioxidant activity was assayed by 2,2 diphenyl-1-picrylhydrazyl radical and beta-carotene bleaching tests. Berberine and palmatine were isolated by flash chromatography and identified by spectrometric methods as main constituents. Non-polar compounds were analysed by gas chromatography and gas chromatography-mass spectrometry. KEY FINDINGS: Extracts, fractions and isolated compounds inhibited AChE and BChE to varying degrees. The methanol fractions exhibited the strongest AChE inhibitory activity with inhibitory concentration 50% (IC50 ) of 7.6 and 16.9 MUg/ml for B. aetnensis and B. libanotica, respectively. The alkaloid fraction of B. aetnensis inhibited AChE (IC50 of 24.5 MUg/ml) and possessed the highest antioxidant activity (IC50 value of 2.2 MUg/ml in beta-carotene-bleaching test after 30 min of incubation). Berberine was more potent of palmatine against AChE (IC50 of 2.2 and 7.4 MUg/ml, respectively). CONCLUSIONS: These findings raise the possibility of developing B. aetnensis and B. libanotica as a promising candidate for the treatment of AD. PMID- 24236983 TI - Pretreatment of SH-SY5Y cells with dicaffeoylquinic acids attenuates the reduced expression of nicotinic receptors, elevated level of oxidative stress and enhanced apoptosis caused by beta-amyloid peptide. AB - OBJECTIVES: This in vitro investigation was designed to examine potential neuroprotection by dicaffeoylquinic acids (diCQAs) extracted from a traditional Chinese medicinal herb herba erigerontis and their effects against the toxicity induced by beta-amyloid peptide (Abeta25-35 ). METHODS: The neuroblastoma SH-SY5Y cell line was treated with Abeta or 3, 4-diCQA, 3, 5-diCQA or 4, 5-diCQA. 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction was assayed by spectrophotometrical method, lipid peroxidation (malondialdehyde) on the basis of the level of thiobarbituric acid-reactive substance, the activity of superoxide dismutase by the xanthine oxidase procedure, the frequency of apoptosis by flow cytometry, and the levels of alpha3 and alpha7 nicotinic acetylcholine receptor (nAChR) subunit proteins by Western blotting. KEY FINDINGS: When the cells were exposed to Abeta25-35 , MTT reduction declined, oxidative stress and apoptosis were enhanced, and the expression of alpha3 and alpha7 nAChR subunit proteins was lowered. Expression of the alpha7 nAChR subunit protein was increased by all three diCQAs, and the level of alpha3 was increased by 3, 5-diCQA and 4, 5-diCQA. Significantly, pretreatment with diCQAs attenuated the neurotoxic effects of Abeta25-35 , a neuroprotective effect in which the upregulation of alpha7 and alpha3 nAChR may be involved. CONCLUSION: The diCQAs exert a protective effect on Abeta-induced neurotoxicity in SH-SY5Y cells and a potential underlying mechanism involving stimulation of nAChRs. PMID- 24236984 TI - Impact of caffeic acid on aluminium chloride-induced dementia in rats. AB - OBJECTIVE: Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease. METHODS: Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3 )-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress. KEY FINDINGS: Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain. CONCLUSION: These findings suggest the antidementia activity of caffeic acid against AlCl3 -induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders. PMID- 24236985 TI - Trehalose rescues Alzheimer's disease phenotypes in APP/PS1 transgenic mice. AB - OBJECTIVE: Alzheimer's Disease (AD) is well characterized by the accumulated Abeta plaque in hippocampus and cerebral cortex concomitant with markedly reduced study and learning ability. Trehalose, a natural disaccharide, has been shown to have neural protective properties and exhibited therapeutic effects in animal models of several neural degenerative disorders. However, the effect of trehalose on AD pathology remains largely unknown. METHODS: In this study, we evaluated the effects of trehalose in APP/PS1 transgenic mice through behaviour tests and biochemical analyses. KEY FINDINGS: We found that the impaired cognitive and learning ability was improved and Abeta deposit in hippocampus was reduced. CONCLUSIONS: These results suggested that trehalose could be a potential therapeutic drug for the treatment of AD. PMID- 24236986 TI - Influence of the formulation on the maximum tolerated doses of brain targeted nanoparticles of gallic acid by oral administration in Wistar rats. AB - OBJECTIVES: The objective of the present investigation was to study the effect of pure gallic acid (GA) and its Tween 80 coated chitosan nanoparticles (cGANP) on the maximum tolerated dose (MTD) using Wistar rats. METHODS: The animals were administered with increasing doses (dose increasing rate = 10%) of GA and cGANP orally for 28 consecutive days until the MTD was found. The animals were monitored for bodyweight, weight indices, behavioural, biochemical and histopathological changes. KEY FINDINGS: The MTD was found to be 750 mg/kg for GA and was increased to 825 mg/kg for cGANP, which indicated a significantly greater tolerance of cGANP. Slight behavioural and biochemical changes were observed above the MTD. At the MTD no significant behavioural, biochemical, histopathological changes were observed. CONCLUSIONS: The brain targeted nanoparticles displayed considerable improvement in the tolerance profile of the drug as compared with the free drug. PMID- 24236987 TI - In-vitro stability and metabolism of a tacrine-silibinin codrug. AB - OBJECTIVES: A tacrine-silibinin codrug showed promising results in pharmacological and toxicity testing, superior to an equimolar mixture of tacrine and silibinin. The aim of this study was to get more information about its stability, possible degradation products, metabolites, and especially its active principle in vitro and in vivo. METHODS: The stability of the codrug was analysed under in-vitro assay conditions. Additionally, its metabolism was investigated using pooled human liver microsomes. Metabolites were identified via liquid chromatography-high resolution electrospray ionization mass spectrometry. Furthermore, the influence of one of the main cleavage products, tacrine hemi succinamide, on viability and mitochondria of hepatic stellate cells was analysed. KEY FINDINGS: The codrug remained stable in culture medium (Dulbecco's modified Eagle's medium) over an incubation period of 24 h, whereas exposition to microsomal enzymes led to rapid cleavage of the ester bond to form silibinin and a tacrine hemi succinamide. In addition, glucuronidated metabolites of both silibinin and the codrug were detected. For the tacrine hemi succinamide, no effects were observed with regard to cell viability and mitochondrial impairment. CONCLUSIONS: This study helps understand and interpret previous results concerning the effects and the absence of toxicity of the tacrine-silibinin codrug and supplies important information for further identification of the active principles of the codrug in vivo. PMID- 24236988 TI - Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats. AB - BACKGROUND AND PURPOSE: Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Delta(9) -tetrahydrocannabinol (THC) and 3,4 methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. EXPERIMENTAL APPROACH: Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. KEY RESULTS: THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. CONCLUSIONS AND IMPLICATIONS: Adolescent exposure of rats to THC and/or MDMA induced long term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. LINKED ARTICLES: This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. PMID- 24236990 TI - Low mortality and low rate of perceived and documented arrhythmias after Cox maze III surgery for atrial fibrillation. AB - BACKGROUND: To report a long-term single-site experience of the cut-and-sew Cox maze III procedure for atrial fibrillation (AF). METHODS: A total of 232 consecutive patients underwent the Cox maze III procedure for symptomatic therapy refractory AF, with concomitant surgery in 34 patients. Follow-up data were obtained from electrocardiograms, patient visits, questionnaires, and medical files. RESULTS: There were 103 patients (44%) with paroxysmal AF during 8.8 +/- 6.5 years and 129 patients (56%) with nonparoxysmal AF for 7.3 +/- 6.7 years. The preoperative New York Heart Association class was better in patients with paroxysmal AF (P < 0.0001); the left ventricular ejection fraction was 59 +/- 7% versus 56 +/- 8%, P = 0.003, and the left atrial area 24 +/- 6 versus 27 +/- 6 cm(2) , P = 0.01. Early and late postoperative adverse events occurred at similar rates. Four patients from each group died of reasons unrelated to surgery. The mean follow-up was 66 +/- 42 (5-155) months. In total, 184/229 (80%) patients were free of documented AF/atrial flutter/atrial tachycardia (AF/AFl/AT) off antiarrhythmic drugs (AA) and 189/229 (83%) on or off AA. The hazard ratio (HR) for paroxysmal versus nonparoxysmal AF patients regarding documented AF/AFl/AT was 0.8 (95% confidence interval [CI] 0.4-1.4; P = 0.40). For patients without versus with concomitant surgery, the corresponding HR was 0.4 (95% CI 0.2-0.8; P = 0.008). Of 197 patients (89%) responding to the questionnaire, 41 had sought care for symptoms of arrhythmia, 29 of whom had documented AF/AFl/AT, whereas another six had other arrhythmias. CONCLUSION: Cut-and-sew Cox maze III surgery provided long-lasting high efficacy, also in patients with nonparoxysmal AF of long duration and/or concomitant surgery, and was associated with low rates of subsequent adverse events. PMID- 24236989 TI - Review article: vitamin D and inflammatory bowel diseases. AB - BACKGROUND: Vitamin D is traditionally associated with bone metabolism. The immunological effects of vitamin D have increasingly come into focus. AIM: To review the evidence supporting a role of vitamin D in inflammatory bowel diseases. METHODS: A comprehensive search was performed on PubMed using the terms 'crohn's disease' 'ulcerative colitis' and 'vitamin D'. RESULTS: Vitamin D deficiency is common in patients with inflammatory bowel diseases (IBD) (16-95%) including those with recently diagnosed disease. Evidence supports immunological role of vitamin D in IBD. In animal models, deficiency of vitamin D increases susceptibility to dextran sodium sulphate colitis, while 1,25(OH)2 D3 ameliorates such colitis. One prospective cohort study found low predicted vitamin D levels to be associated with an increased risk of Crohn's disease (CD). Limited data also suggest an association between low vitamin D levels and increased disease activity, particularly in CD. In a large cohort, vitamin D deficiency (<20 ng/mL) was associated with increased risk of surgery (OR 1.8, 95% CI 1.2-2.5) in CD and hospitalisations in both CD (OR 2.1, 95% CI 1.6-2.7) and UC (OR 2.3, 95% CI 1.7 3.1). A single randomised controlled trial demonstrated that vitamin D supplementation may be associated with reduced frequency of relapses in patients with CD compared with placebo (13% vs. 29%, P = 0.06). CONCLUSIONS: There is growing epidemiological evidence to suggest a role for vitamin D deficiency in the development of IBD and also its influence on disease severity. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation. PMID- 24236992 TI - The mediating effects of coping on the stress and health relationships among nursing students: a structural equation modelling approach. AB - AIMS: To test the impact of stress on psychological and physical health, and examine the mediating effects of coping on the stress-health relationships among nursing students. BACKGROUND: Stress is associated with various physical and psychological symptoms in nursing students. Numerous studies examined the relationships among stress, coping and health; nevertheless, a mechanism of coping has not been fully explored in Thai nursing students. DESIGN: This study adopted a cross-sectional, descriptive correlational research design. METHODS: A convenience sample of 335 nursing students were recruited from a University in Thailand from 2005-2007. We used self-reported questionnaires to collect information; and analysed data using descriptive statistics and structural equation modelling. RESULTS: Nursing students with high levels of stress reported poorer physical health and higher psychological distress. Stress had a stronger effect and explained more variances on psychological distress than on poor physical health. The partial mediation of coping was observed. Specifically, 77.00% of the effects of stress on poor physical health and 11.30% on psychological distress were mediated by coping. CONCLUSION: Evidence from this study contributes to the nursing science and has implications to nursing practice. Stress among nursing students should be monitored and effectively managed to prevent deleterious effects on their health. Nursing interventions focusing on coping skill training could be developed and delivered. Future research may examine the effectiveness of the interventions and/or to further explore variables associated with psychological distress in nursing students. PMID- 24236993 TI - Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats. AB - Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time-concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean +/- SE (range) bioavailability was 36.6 +/- 5.2 (12.7-49.5), 44.2 +/- 7.9 (18.7-70.5), 22.4 +/- 6.9 (6.4-43.4), and 18.8 +/- 2.0 (12.9-23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone. PMID- 24236995 TI - Investigation of the putative associations between dairy consumption and incidence of type 1 and type 2 diabetes. AB - A growing body of evidence suggests a possible relationship between the consumption of dairy products and the incidence of diabetes. A positive correlation between the early introduction of dairy in infancy and the incidence of type 1 diabetes (T1D) in genetically predisposed infants has been suggested by studies on rodents and humans. However, the lines of evidence supporting this association, including epidemiological studies and the observation of antibodies to bovine serum albumin, beta-casein and bovine insulin in the serum of patients with T1D, are not without controversy. On the other hand, an inverse relationship between the consumption of dairy foods and the development of metabolic syndrome and/or type 2 diabetes (T2D) has been implied by epidemiological studies. Several dairy components, especially milk proteins, are believed to play a role in the beneficial effect of dairy consumption on glucose regulation by modulation of incretin hormones. Other dietary factors have also been associated with the incidence of T1D and T2D, indicating that dairy foods might be only one among many dietary agents possibly implicated in the development of diabetes. The present paper critically reviews the evidence and plausible mechanisms for the putative associations between dairy food consumption and incidence of T1D and T2D. PMID- 24236994 TI - Leveraging electronic health records to develop measurements for processes of care. AB - OBJECTIVES: To assess the reliability of data in electronic health records (EHRs) for measuring processes of care among primary care physicians (PCPs) and examine the relationship between these measures and clinical outcomes. DATA SOURCES/STUDY SETTING: EHR data from 15,370 patients with diabetes, 49,561 with hypertension, in a group practice serving four Northern California counties. STUDY DESIGN/METHODS: Exploratory factor analysis (EFA) and multilevel analyses of the relationships between processes of care variables and factor scales with control of hemoglobin A1c, blood pressure (BP), and low density lipoprotein (LDL) among patients with diabetes and BP among patients with hypertension. PRINCIPAL FINDINGS: Volume of e-messages, number of days to the third-next-available appointment, and team communication emerged as reliable factors of PCP processes of care in EFA (Cronbach's alpha=0.73, 0.62, and 0.91). Volume of e-messages was associated with higher odds of LDL control (<=100) (OR=1.13, p<.05) among patients with diabetes. Frequent in-person visits were associated with better BP (OR=1.02, p<.01) and LDL control (OR=1.01, p<.01) among patients with diabetes, and better BP control (OR=1.04, p<.01) among patients with hypertension. CONCLUSIONS: The EHR offers process of care measures which can augment patient reported measures of patient-centeredness. Two of them are significantly associated with clinical outcomes. Future research should examine their association with additional outcomes. PMID- 24236996 TI - An overview on chemical composition, bioactivity and processing of leaves of Cinnamomum tamala. AB - Dried leaves of Cinnamomum tamala, also known as Indian bay leaves, are a lesser known spice used in the Indian subcontinent. It imparts a warm, peppery, clove cinnamon like flavor to a variety of food preparations. Besides food applications, the leaves have also been traditionally used for curing a number of ailments and for other perceived health benefits. They find mention in the Aurvedic, Yunani, and other traditional medicinal literature. This review summarizes the effect of Cinnamomum tamala leaves on biological systems such as immune system, gastro-intestinal tract, liver and its antioxidant, antidiabetic, anti-inflammatory, anticancer, and antimicrobial activity. Chemical components that may be responsible for its flavor as well as bioactivity, have also been discussed. PMID- 24236997 TI - A critical review on the spray drying of fruit extract: effect of additives on physicochemical properties. AB - Spray drying accomplishes drying while particles are suspended in the air and is one method in the family of suspended particle processing systems, along with fluid-bed drying, flash drying, spray granulation, spray agglomeration, spray reaction, spray cooling, and spray absorption. This drying process is unique because it involves both particle formation and drying. The present paper reviews spray drying of fruit extracts, such as acai, acerola pomace, gac, mango, orange, cactus pear, opuntia stricta fruit, watermelon, and durian, and the effects of additives on physicochemical properties such as antioxidant activity, total carotenoid content, lycopene and beta-carotene content, hygroscopy, moisture content, volatile retention, stickiness, color, solubility, glass transition temperature, bulk density, rehydration, caking, appearance under electron microscopy, and X-ray powder diffraction. The literature clearly demonstrates that the effect of additives and encapsulation play a vital role in determining the physicochemical properties of fruit extract powder. The technical difficulties in spray drying of fruit extracts can be overcome by modifying the spray dryer design. It also reveals that spray drying is a novel technology for converting fruit extract into powder form. PMID- 24236998 TI - Polysaccharides in Lentinus edodes: isolation, structure, immunomodulating activity and future prospective. AB - Lentinus edodes has been valued as edible and medical resources. Polysaccharides have been known to be the most potent antitumor and immunomodulating substance in Lentinus edodes. In this review, we summarize the current knowledge of the polysaccharides isolated from Lentinus edodes, including extraction and purification methods, chemical structure and chain conformation, the effects on innate and adaptive immunity and their mechanism, relationship between structure and function, and the future prospects. PMID- 24236999 TI - Review of the regulation of veterinary drugs and residues in South Africa. AB - The food safety risk analysis framework of the FAO/WHO is used in the review of veterinary drug and residue regulation in South Africa to determine possible inefficiencies within this system. Results indicate that a variety of challenges relating to the processes of risk assessment, management, and communication do exist, although these occur within a fragmented system of legislation, functions, and structures. Addressing these challenges therefore requires a change to a more collaborative and integrated system. It is indicated that for such a change, the underlying challenges of inadequate horizontal communication, poor conceptualization, and awareness of functions of the system are required to be dealt with. PMID- 24237000 TI - Perspectives on the utilization of aquaculture coproduct in Europe and Asia: prospects for value addition and improved resource efficiency. AB - Aquaculture has often been criticized for its environmental impacts, especially efficiencies concerning global fisheries resources for use in aquafeeds among others. However, little attention has been paid to the contribution of coproducts from aquaculture, which can vary between 40% and 70% of the production. These have often been underutilized and could be redirected to maximize the efficient use of resource inputs including reducing the burden on fisheries resources. In this review, we identify strategies to enhance the overall value of the harvested yield including noneffluent processing coproducts for three of the most important global aquaculture species, and discuss the current and prospective utilization of these resources for value addition and environmental impact reduction. The review concludes that in Europe coproducts are often underutilized because of logistical reasons such as the disconnected nature of the value chain, and perceived legislative barriers. However, in Asia, most coproducts are used, often innovatively but not to their full economic potential and sometimes with possible human health and biosecurity risks. These include possible spread of diseased material and low traceability in some circumstances. Full economic and environmental appraisal is long overdue for the current and potential strategies available for coproduct utilization. PMID- 24237001 TI - Prebiotics: application in bakery and pasta products. AB - The concept of functional foods has markedly moved toward gastrointestinal health. The prebiotic approach aims at achieving favorable milieu in the human gut by stimulating beneficial bacteria. Several food products act as substrates for the application of prebiotic substances and bakery products are one such category. The trend of increasing consumption of bakery products justifies the choice of using them as vehicles for delivering the prebiotic compounds. Apart from the health benefits, the prebiotic compounds also have nutritional and technological effects in the food matrix. In addition to increasing the fiber content, the candidate prebiotics also affect the rheology and final quality of bakery products. The prebiotic compounds are selected accordingly to confer desirable properties in the final product. The health advantages of prebiotics being well established, the technological advantages in bakery products such as bread and biscuits and extruded product such as pasta are discussed elaborately. PMID- 24237002 TI - Epidemiological evidence linking tea consumption to human health: a review. AB - Tea has been widely consumed around the world for thousands of years and drinking tea is a daily habit for people of all ages. Tea is a major source of flavonoids, which have become well known as antioxidants. Tea also contains caffeine and theanine, which have been found to associate with health benefits. Many animal and epidemiological studies have been conducted to investigate the link between tea consumption and human health. However, common questions that arise about tea consumption include: whether all teas are the same, why drinking tea is linked with health benefits, how do the different ways of tea preparation impact on availability of tea components, how much and how long a person should consume tea to obtain health benefits, and whether there is any negative health effect associated with drinking tea. To answer these questions, this paper outlines the tea components and their link to human health, discusses major factors affecting availability of tea components in a tea cup, and reviews the latest epidemiological evidence linking tea consumption to human health. PMID- 24237003 TI - Probiotics: a comprehensive approach toward health foods. AB - Food products containing probiotics and prebiotics are an important development in Health foods, which enhance health promoting microbial flora in the intestine. Probiotic refers to viable microorganism that promotes or support a beneficial balance of the autochthonous microbial population of the gastrointestinal tract. A number of genera of bacteria (and yeast) are used as probiotics, including Lactobacillus, Leuconostoc, Pediococcus, Bifidobacterium, Saccharomyces, and Enterococcus, but the main species believed to have probiotic characteristics are Lactobacillus acidophilus, Bifidobacterium spp., and L. casei. Probiotics can reduce diarrheal incidence, lactose intolerance, lower serum cholesterol, stimulate the immune system, control infections, act as antibiotics, suppress tumors, and protect against colon or bladder cancer by maintaining a healthy intestinal microflora balance. Lactic acid bacteria produce biopreservatives such as lactic acid, hydrogen peroxide, and bacteriocins that are used to retard both spoilage and the growth of pathogenic bacteria. Food, particularly dairy products are considered as an ideal vehicle for delivering probiotic bacteria to the human gastrointestinal tract. Cereals being rich source of prebiotics such as beta glucan and arabinoxylan, galacto-, and fructooligosaccharides are considered for development of probiotic foods. Good manufacturing practices must be applied in the manufacture of probiotic foods with quality assurance, and shelf-life conditions established. PMID- 24237004 TI - Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. AB - OBJECTIVE: During the past two decades, professional associations, accrediting bodies, and payors have made post-surgical pain treatment a high priority. In light of the disappointing findings in previous surveys, a survey was conducted to assess patient perceptions and characterize patient experiences/levels of satisfaction with post-surgical pain management. RESEARCH DESIGN AND METHODS: Survey included a random sample of US adults who had undergone surgery within 5 years from the survey date. Participants were asked about their concerns before surgery, severity of perioperative pain, pain treatments, perceptions about post surgical pain and pain medications, and satisfaction with treatments they received. RESULTS: Of the 300 participants, ~86% experienced pain after surgery; of these, 75% had moderate/extreme pain during the immediate post-surgical period, with 74% still experiencing these levels of pain after discharge. Post surgical pain was the most prominent pre-surgical patient concern, and nearly half reported they had high/very high anxiety levels about pain before surgery. Approximately 88% received analgesic medications to manage pain; of these, 80% experienced adverse effects and 39% reported moderate/severe pain even after receiving their first dose. STUDY LIMITATIONS: Key study limitations include the relatively small population size, potential for recall bias associated with the 14-month average time delay from surgery date to survey date, and the inability to account for influences of type of surgery and intraoperative anesthetic/analgesic use on survey results. CONCLUSIONS: Despite heightened awareness and clinical advancements in pain management, there has been little improvement in post-surgical analgesia as measured by this survey of post surgical patients. PMID- 24237005 TI - Measuring protein-ligand interactions using liquid sample desorption electrospray ionization mass spectrometry. AB - We have previously shown that liquid sample desorption electrospray ionization mass spectrometry (DESI-MS) is able to measure large proteins and noncovalently bound protein complexes (to 150 kDa) (Ferguson et al., Anal. Chem. 2011, 83, 6468 6473). In this study, we further investigate the application of liquid sample DESI-MS to probe protein-ligand interactions. Liquid sample DESI allows the direct formation of intact protein-ligand complex ions by spraying ligands toward separate protein sample solutions. This type of "reactive" DESI methodology can provide rapid information on binding stiochiometry, selectivity, and kinetics, as demonstrated by the binding of ribonuclease A (RNaseA, 13.7 kDa) with cytidine nucleotide ligands and the binding of lysozyme (14.3 kDa) with acetyl chitose ligands. A higher throughput method for ligand screening by liquid sample DESI was demonstrated, in which different ligands were sequentially injected as a segmented flow for DESI ionization. Furthermore, supercharging to enhance analyte charge can be integrated with liquid sample DESI-MS, without interfering with the formation of protein-ligand complexes. PMID- 24237007 TI - Temperature management and modern post-cardiac arrest care. PMID- 24237008 TI - Sexual practices, identities and health among women who have sex with women in Lesotho - a mixed-methods study. AB - Despite the high prevalence of HIV and STIs among women in Africa and the growing literature on HIV and STIs among women who have sex with women, research on the sexual health of women who have sex with women in Africa is scant. This study used mixed methods to describe sexual identity, practices and health among women who have sex with women in Lesotho. Most respondents (48%) described themselves as lesbian, 29% as bisexual and 23% as heterosexual. Almost half (45%) had disclosed their same-sex attraction to family, but only 25% had done so with healthcare workers. A total of 8% reported having HIV. Self-reported HIV was associated with having three or more male partners, having male and female partners at the same time and having a history of STIs. Gender norms, the criminalisation of homosexuality, varied knowledge of, and access to, safer-sex strategies, and mixed experiences of HIV/STI testing and sexual healthcare provided social and structural contexts for HIV- and STI-related vulnerability. PMID- 24237009 TI - Neutropenia associated with antihuman neutrophil antibodies following allogeneic hematopoietic stem cell transplantation. PMID- 24237010 TI - Clinical monosensitivity to salmon and rainbow trout: a case report. PMID- 24237011 TI - "I want to know more about who we are": new directions for research with older lesbians. AB - Previous literature has consistently discussed reoccurring issues with conducting research in the gay and lesbian community and, for the purposes of this article, particularly the older lesbian community. Issues with sampling, including gaining access, ethical considerations, and conceptual definitions are ongoing struggles repeated within the literature. This article provides the experience of a research team in conducting such research and presents the viable solutions and ongoing barriers, as well as newer considerations that future research must take into account. In addition, this article provides the viewpoint of 189 older lesbians on the future research needs within their community. PMID- 24237015 TI - Engineering the MEP pathway enhanced ajmalicine biosynthesis. AB - The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway genes encoding DXR and MECS from Taxus species and STR from Catharanthus roseus were used to genetically modify the ajmalicine biosynthetic pathway in hairy root cultures of C. roseus. As expected, the STR-overexpressed root cultures showed twofold higher accumulation of ajmalicine than the control. It was important to discover that overexpression of the single DXR or MECS gene from the MEP pathway also remarkably enhanced ajmalicine biosynthesis in transgenic hairy root cultures, and this suggested that engineering the MEP pathway by overexpression of DXR or MECS promoted the metabolic flux into ajmalicine biosynthesis. The transgenic hairy root cultures with co-overexpression of DXR and STR or MECS and STR had higher levels of ajmalicine than those with overexpression of a single gene alone such as DXR, MECS, and STR. It could be concluded that transgenic hairy root cultures harboring both DXR/MECS and STR possessed an increased flux in the terpenoid indole alkaloid biosynthetic pathway that enhanced ajmalicine yield, which was more efficient than cultures harboring only one of the three genes. PMID- 24237016 TI - The duty of disclosure in the post-Therasense landscape. PMID- 24237017 TI - Devising a patent strategy to protect the IP of biologics in light of ambiguities, loopholes and pitfalls in the regulatory scheme. PMID- 24237006 TI - Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. AB - BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. CONCLUSIONS: In unconscious survivors of out-of hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.). PMID- 24237018 TI - Supplementary protection certificates on reformulations and new uses after Neurim: where do we go from here? PMID- 24237019 TI - Navigating the maze of IP/regulatory rights in the EU: the complex interaction between the SPC and Pediatric Regulations. PMID- 24237020 TI - Diagnostic claims post-Mayo and Myriad: the pile-up begins. PMID- 24237022 TI - The changing relationship between patent owners and researchers. PMID- 24237023 TI - The ITC as an attractive patent litigation forum for the biotechnology and pharmaceutical industry. PMID- 24237026 TI - Learning from practice: compulsory licensing cases and access to medicines. AB - Compulsory license is one of the safeguards that international IP law provides to address the undesired effects of pharmaceutical patents on access to important medicines. This article looks into three important case examples to analyze the mechanism's effectiveness and feasibility: the first uses of the newer compulsory license regime established in 2003 under the WTO legislative framework to export medicines to third countries, which lack pharmaceutical manufacturing capacities; and further, the first compulsory license grant in India in March 2012. The case analyses are based on the historical, factual and legal background. They reveal the main challenges of the 2003 WTO regime, including the lack of economic incentives for the generic pharmaceutical companies' participation. In the case of India's compulsory license grant, the article takes as in depth look into possible reasons for the reluctance to use the safeguard until recently, and the important aspects and implications of the Indian authorization to manufacture and sell a generic version of a patented cancer drug. PMID- 24237027 TI - Oligonucleotides for upregulating gene expression. AB - Over the recent decade oligonucleotides have become an important new class of molecules, allowing therapeutic intervention through targets previously thought 'undruggable'. One of the new avenues opened up by oligonucleotide-based drugs was specific gene upregulation, which, historically, has been difficult to achieve using small-molecule drugs. This article will focus on patents covering this important development in the oligonucleotide field and highlight the different mechanisms through which the oligonucleotide-mediated gene upregulation can work, including inhibition of activity of natural antisense transcripts, interaction with promoter binding sites of noncoding regulatory RNAs, blocking of regulatory and/or miRNA binding sites in 3' UTRs, blocking splice inhibitor/enhancer sites or blocking interactions with polycomb repressive complex 2. Understanding the particular mechanism through which an oligonucleotide drug exerts its effects is highly important in drug development, as it determines the design of the drug molecule. PMID- 24237028 TI - The patent situation concerning the treatment of diseases associated with autoantibodies directed against G-protein-coupled receptors. AB - Agonist-like autoantibodies against receptors of the G-protein-coupled signal cascade have been identified as the pathogenic principle for a variety of diseases, especially those of the heart and vascular system. Consequently, the elimination or neutralization of such autoantibodies is an advised goal for causal therapeutic intervention. This article provides a short, noncomplete overview about remarkable developmental strategies and technical solutions for the therapy of diseases, associated with G-protein-coupled receptor autoantibodies. According to the immunoglobulin nature of the therapeutic target, several strategies are possible, such as the use of the autoantibody epitope sequences as competitors or binding molecules for specific autoantibody elimination by apheresis. Complete immunoglobulin elimination, as is currently being tested in autoantibody-positive cardiomyopathy patients, would be a nonspecific solution as would the use of immunosuppressant agents. The use of autoantibody-binding molecules on an aptamer basis for neutralization or elimination is a newly developed specific therapeutic option. PMID- 24237029 TI - Monoclonal antibodies based on hybridoma technology. AB - Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs. PMID- 24237032 TI - Recent patents on stimuli responsive hydrogel drug delivery system. AB - Hydrogels are cross-linked hydrophilic polymer structures that imbibe large quantities of water or biological fluids. Hydrogels are an upcoming class of polymer-based controlled release drug delivery systems, embracing numerous biomedical and pharmaceutical applications. Hydrogels are swellable polymeric materials, and are being widely investigated as a carrier for drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli responsive changes in their structural network and hence leading to the drug release. The present manuscript is concerned with the classification, method of preparation; application in drug deliveryand FDA approved market products of hydrogels with the patent review on hydrogel composition and its manufacturing process. It also highlights recent advances in hydrogel drug delivery especially stimuli-responsive hydrogel and its patents. This patent review is useful in the synthesis methods of hydrogel drug delivery and its application. PMID- 24237030 TI - Targeting inflammation: multiple innovative ways to reduce prostaglandin E2. AB - The PGE2 pathway is important in inflammation-driven diseases and specific targeting of the inducible mPGES-1 is warranted due to the cardiovascular problems associated with the long-term use of COX-2 inhibitors. This review focuses on patents issued on methods of measuring mPGES-1 activity, on drugs targeting mPGES-1 and on other modulators of free extracellular PGE2 concentration. Perspectives and conclusions regarding the status of these drugs are also presented. Importantly, no selective inhibitors targeting mPGES-1 have been identified and, despite the high number of published patents, none of these drugs have yet made it to clinical trials. PMID- 24237033 TI - Gastroprotective effects (in rodents) of a flavonoid rich fraction obtained from Syngonanthus macrolepsis. AB - OBJECTIVES: Syngonanthus macrolepis, popularly known in Brazil as 'sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats. METHODS: The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated. KEY FINDINGS: The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation. CONCLUSIONS: The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors. PMID- 24237034 TI - ICD lead parameters, performance, and adverse events following continuous-flow LVAD implantation. AB - BACKGROUND: Ventricular arrhythmias (VAs) in the months following continuous-flow left ventricular assist devices (LVADs) implantation are common and associated with increased morbidity and mortality. We sought to evaluate for changes in implantable cardioverter defibrillator (ICD) performance following LVAD implantation. METHODS: We retrospectively reviewed the ICD interrogation reports and medical records of patients who received a continuous-flow LVAD at the University of Chicago Medical Center between January 2008 and December 2010. Patients who did not have an ICD prior to LVAD implantation were excluded. RESULTS: Forty-four patients were included. Median right ventricular lead sensing amplitude decreased from 10.0 (interquartile range 7.6-13.6) mV prior to LVAD to 7.9 (5.9-9.3) mV after LVAD implantation (P < 0.01). Significant reductions in sensing threshold were associated with smaller lead diameters, smaller pace/sense electrode surface areas, and Medtronic ICD leads (Medtronic Inc., Minneapolis, MN, USA). Lead impedance and capture threshold did not change significantly. ICD related adverse events occurred in 30% of patients and led to ICD modification in 18% of patients. CONCLUSIONS: Implantation of a continuous-flow LVAD is associated with changes in the performance of preexisting ICDs. ICD-related adverse events were encountered following LVAD implantation in this cohort, and at times resulted in invasive and noninvasive ICD system modification. Reductions in ICD sensing threshold after LVAD implantation may adversely affect ICD function. Formal ICD interrogation in addition to the regular follow-up testing is warranted post-LVAD. PMID- 24237035 TI - Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men. AB - There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of alpha4beta7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10 nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3 h after 10 mg ATRA. We then evaluated the effect of 10 mg ATRA given 1 h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] C(max) was 26.2 (11.7-39.5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P = 0.02) and protein (P = 0.04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant. PMID- 24237036 TI - Large-scale quantification of single amino-acid variations by a variation associated database search strategy. AB - Global quantification of the single amino-acid variations (SAAVs) is essential to investigate the roles of SAAVs in disease progression. However, few efforts have been made on this issue due to the lack of high -throughput approach. Here we presented a strategy by integration of the stable isotope dimethyl labeling with variation-associated database search to globally quantify the SAAVs at the first time. A protein database containing 87,745 amino acid variant sequences and 73,910 UniProtKB/Swiss-Prot canonical protein entries was constructed for database search, and higher energy collisional dissociation combined with collision-induced dissociation fragmentation modes were applied to improve the quantification coverage of SAAVs. Compared with target proteomics in which only a few sites could be quantified, as many as 282 unique SAAVs sites were quantified between hepatocellular carcinoma (HCC) and normal human liver tissues by our strategy. The variation rates in different samples were evaluated, and some interesting SAAVs with significant increase normalized quantification ratios, such as T1406N in CPS1 and S197R in HTATIP2, were observed to highly associate with HCC progression. Therefore, the newly developed strategy enables the large scale comparative analysis of variations at the protein level and holds a promising future in the research related to variations. PMID- 24237037 TI - Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease. AB - BACKGROUND: Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD). AIM: To investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations. METHODS: This multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight-based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250-400 pmol/8 * 10(8) red blood cells (RBC), or to a maximal dose of 4 mg/kg/day. RESULTS: After randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention-to-treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight-based arm (P = 0.11). In per-protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight-based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 * 10(8) RBC respectively (P = 0.07). CONCLUSIONS: Despite trends favouring individualised over weight-based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. [Clinicaltrials.Gov Identifier Nct00113503]. PMID- 24237038 TI - The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer's disease. AB - BACKGROUND: Biochemical changes in the cerebrospinal fluid (CSF) could reflect pathophysiological processes in Alzheimer's disease (AD). However, it is still not clear how these processes correlate with grey matter (GM) volume and microstructural changes in the brain. OBJECTIVE: To assess the relationship between CSF biomarkers and structural brain changes in AD. DESIGN AND SETTING: Cross-sectional study in a memory clinic-based sample. SUBJECTS: A total of 78 subjects were included in the study: 22 with subjective cognitive impairment (SCI), 35 with mild cognitive impairment (MCI) and 21 with AD. MAIN OUTCOME MEASURES: Voxel-wise correlations between CSF biomarkers, including beta amyloid42 (Abeta42), tau phosphorylated at position threonine 181 and total tau protein, and GM volume, self-diffusion fractional anisotropy (FA) and mean diffusivity (MD) maps using voxel-based morphometry and tract-based spatial statistical analyses. FA and MD maps were obtained using diffusion tensor imaging. RESULTS: In the whole sample (patients with SCI, MCI and AD), there was positive correlation between GM volume and Abeta42 concentration, and negative correlation with total tau protein. Higher FA was only related to higher concentration of Abeta42. MD showed significant negative correlation with Abeta42 and positive correlation with T-tau levels. The majority of brain regions with significant correlation with CSF biomarkers overlapped with the default mode network and extended to the adjacent white matter. CONCLUSIONS: Early AD pathological changes can be detected with voxel-based morphometric analysis and diffusion tensor imaging measurements. Furthermore, there was an association between CSF AD biomarkers and structural brain changes in areas related to the default mode network. PMID- 24237039 TI - 3-Azatetracyclo[5.2.1.1(5,8).0(1,5)]undecane derivatives: from wild-type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutant. AB - We have synthesized and characterized a series of compounds containing the 3 azatetracyclo[5.2.1.1(5,8).0(1,5)]undecane scaffold designed as analogues of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (WT) M2 channel and the amantadine-resistant A/M2 S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the WT ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC50. None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual WT and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays. PMID- 24237040 TI - Exploring the sensitivity of speech-in-noise tests for noise-induced hearing loss. AB - OBJECTIVE: Recently, the digit triplet test was shown to be a sensitive speech-in noise test for early high-frequency hearing loss in noise-exposed workers. This study investigates if a further improvement is achieved when using a closed set of consonant-vowel-consonant (CVC) speech items with the same vowel, and/or a low pass (LP) filtered version of the standard speech-shaped noise. DESIGN: Speech reception thresholds in noise were gathered for the digit triplet, CVC, and CVC_LP test and compared to the high-frequency pure-tone average (PTA). STUDY SAMPLE: 118 noise-exposed workers showing a wide range of high-frequency hearing losses. RESULTS: For the 84 Dutch-speaking participants, the CVC test showed an increased measurement error and a decreased between-subject variation, leading to a weaker correlation with the PTA2,3,4,6 (R = 0.64) and thus a lower sensitivity compared to the digit triplet test (R = 0.86). However, the use of LP-filtered noise resulted in a sensitivity improvement (R = 0.79 versus R = 0.64) due to the large increase in between-subject spread. Similar trends were found for the 34 French-speaking workers. CONCLUSIONS: Using CVC words with the same vowel could not increase the sensitivity to detect isolated high-frequency hearing loss. With LP-filtered noise, test sensitivity improved, but it did not surpass the original digit triplet test. PMID- 24237041 TI - Effect of companding on speech recognition in quiet and noise for listeners with ANSD. AB - OBJECTIVE: The present study assesses the effect of companding on speech perception in quiet and noise for listeners with auditory neuropathy spectrum disorder (ANSD). DESIGN: Speech perception was assessed using speech reception threshold in noise (SRTn) for sentences and consonant identification in quiet and at different signal-to-noise ratios (15, 10, 5, and 0 dB SNR). STUDY SAMPLE: Ten ANSD listeners and normal-hearing listeners participated in the study. RESULTS: ANSD listeners required significantly higher SRTn when compared to the normal hearing listeners. Companding reduced SRTn more significantly in listeners with ANSD, but for normal-hearing listeners there was only a marginal reduction. In the consonant identification task, ANSD listeners performed poorer than normal hearing listeners in quiet and noise. Companding improved consonant identification in quiet and at 15 dB SNR for listeners with ANSD, whereas no improvement was observed in normal-hearing listeners. CONCLUSION: Results of the present study demonstrate that companding improved speech perception in quiet and noise for ANSD listeners. The amount of improvement is higher at higher SNRs. In normal-hearing listeners, companding showed marginal improvement in both quiet and noise. The findings are discussed for rehabilitation of ANSD listeners by hearing aids which incorporate the companding strategy. PMID- 24237042 TI - Effect of chitosan on Salmonella Typhimurium in broiler chickens. AB - Public concern with the incidence of antibiotic-resistant bacteria, particularly among foodborne pathogens such as Salmonella, has been challenging the poultry industry to find alternative means of control. The purposes of the present study were to evaluate in vitro and in vivo effects of chitosan on Salmonella enterica serovar Typhimurium (ST) infection in broiler chicks. For in vitro crop assay experiments, tubes containing feed, water, and ST were treated with either saline as a control or 0.2% chitosan. The entire assay was repeated in three trials. In two independent in vivo trials, 40 broiler chicks were assigned to an untreated control diet or dietary treatment with 0.2% chitosan for 7 days (20 broiler chicks/treatment). At day 4, chicks were challenged with 2*105 colony-forming units (CFU) ST/bird. In a third in vivo trial, 100 broiler chicks were assigned to untreated control diet or dietary treatment with 0.2% chitosan for 10 days (50 broiler chicks/treatment) to evaluate ST horizontal transmission. At day 3, 10 birds were challenged with 105 CFU ST/bird, and the remaining nonchallenged birds (n=40) were kept in the same floor pen. In all three in vitro trials, 0.2% chitosan significantly reduced total CFU of ST at 0.5 and 6 h postinoculation compared with control (p<0.05). In two in vivo trials, at 7 days, dietary 0.2% chitosan significantly reduced total CFU of recovered ST in the ceca in both experiments. Dietary 0.2% chitosan significantly reduced total ST CFU recovered in the ceca of horizontally challenged birds in the third in vivo trial. Chitosan at 0.2% significantly reduced the CFU of recovered ST in vitro and in vivo, proving to be an alternative tool to reduce crop, ceca, and consequently carcass ST contamination as well as decreasing the amount of ST shed to the environment. PMID- 24237043 TI - Efficiency of U.S. dialysis centers: an updated examination of facility characteristics that influence production of dialysis treatments. AB - OBJECTIVE: To explore the relative efficiency of dialysis facilities in the United States and identify factors that are associated with efficiency in the production of dialysis treatments. DATA SOURCES/STUDY SETTING: Medicare cost report data from 4,343 free-standing dialysis facilities in the United States that offered in-center hemodialysis in 2010. STUDY DESIGN: A cross-sectional, facility-level retrospective database analysis, utilizing data envelopment analysis (DEA) to estimate facility efficiency. DATA COLLECTION/EXTRACTION METHODS: Treatment data and cost and labor inputs of dialysis treatments were obtained from 2010 Medicare Renal Cost Reports. Demographic data were obtained from the 2010 U.S. Census. PRINCIPAL FINDINGS: Only 26.6 percent of facilities were technically efficient. Neither the intensity of market competition nor the profit status of the facility had a significant effect on efficiency. Facilities that were members of large chains were less likely to be efficient. Cost and labor savings due to changes in drug protocols had little effect on overall dialysis center efficiency. CONCLUSIONS: The majority of free-standing dialysis facilities in the United States were functioning in a technically inefficient manner. As payment systems increasingly employ capitation and bundling provisions, these institutions will need to evaluate their efficiency to remain competitive. PMID- 24237044 TI - Response: Domino liver transplantation as a valuable option. PMID- 24237045 TI - Solution processable benzooxadiazole and benzothiadiazole based D-A-D molecules with chalcogenophene: field effect transistor study and structure property relationship. AB - We present here the physicochemical characterization of a series of D-A-D type molecules which comprise benzooxadiazole (BDO) and benzothiadiazole (BDT) core symmetrically linked to two aromatic-heterols (furan (F), thiophene (T) and selenophene (Se)) at 4 and 7-positions. The molecular structures of four compounds 2 (T-BDO-T), 3 (Se-BDO-Se), 5 (T-BDT-T), and 6 (Se-BDT-Se) were determined by single-crystal X-ray diffraction. The combination of chalcogen atoms of benzochalcogenadiazole and chalcogenophene in D-A-D molecules has significant impact on their molecular packing in crystal structures. Structural analyses and theoretical calculations showed that all the molecules are nearly planar. Crystal structures of 2, 3, 5, and 6 showed significant short range interactions such as pi...pi, CH...pi, S...pi, Se...pi, N...H, O...H, S...H, Se...H, S...O, and Se...N interactions, which influence crystal packing and orientation of the capped aromatic-heterol rings with respect to the central BDO or BDT unit. The pi-stacking interactions have been observed via intermolecular overlap of the donor with acceptor units of the adjacent molecules which facilitate the charge transport process. Good thermal stability and solubility in common organic solvents make them good candidate for flexible electronics. Interestingly, the molecules 2, 3, and 6 have the propensity to form ordered crystallites when sheared during the drying process in the thin films. Devices based on these solution processable all organic FETs demonstrated hole mobility as high as 0.08 cm(2) V(-1) s(-1) and Ion/Ioff ratio of 10(4). PMID- 24237048 TI - The process and utility of classification and regression tree methodology in nursing research. AB - AIM: This paper presents a discussion of classification and regression tree analysis and its utility in nursing research. BACKGROUND: Classification and regression tree analysis is an exploratory research method used to illustrate associations between variables not suited to traditional regression analysis. Complex interactions are demonstrated between covariates and variables of interest in inverted tree diagrams. DESIGN: Discussion paper. DATA SOURCES: English language literature was sourced from eBooks, Medline Complete and CINAHL Plus databases, Google and Google Scholar, hard copy research texts and retrieved reference lists for terms including classification and regression tree* and derivatives and recursive partitioning from 1984-2013. DISCUSSION: Classification and regression tree analysis is an important method used to identify previously unknown patterns amongst data. Whilst there are several reasons to embrace this method as a means of exploratory quantitative research, issues regarding quality of data as well as the usefulness and validity of the findings should be considered. IMPLICATIONS FOR NURSING RESEARCH: Classification and regression tree analysis is a valuable tool to guide nurses to reduce gaps in the application of evidence to practice. With the ever-expanding availability of data, it is important that nurses understand the utility and limitations of the research method. CONCLUSION: Classification and regression tree analysis is an easily interpreted method for modelling interactions between health-related variables that would otherwise remain obscured. Knowledge is presented graphically, providing insightful understanding of complex and hierarchical relationships in an accessible and useful way to nursing and other health professions. PMID- 24237049 TI - Low-cost silicone imaging casts for zebrafish embryos and larvae. AB - Due to their size and optical clarity, zebrafish embryos have long been appreciated for their usefulness in time-lapse confocal microscopy. Current methods of mounting zebrafish embryos and larvae for imaging consist mainly of mounting in low percentage, low melting temperature agarose in a Petri dish. Whereas imaging methods have advanced greatly over the last two decades, the methods for mounting embryos have not changed significantly. In this article, we describe the development and use of 3D printed plastic molds. These molds can be used to create silicone casts and allow embryos and larvae to be mounted with a consistent and reproducible angle, and position in X, Y, and Z. These molds are made on a 3D printer and can be easily and cheaply reproduced by anyone with access to a 3D printer, making this method accessible to the entire zebrafish community. Molds can be reused to create additional casts, which can be reused after imaging. These casts are compatible with any upright microscope and can be adapted for use on an inverted microscope, taking the working distance of the objective used into account. This technique should prove to be useful to any researcher imaging zebrafish embryos. PMID- 24237050 TI - Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles for the treatment of intraperitoneal ovarian cancer xenografts. AB - Ultrasound-targeted microbubble destruction (UTMD) is a promising technique to facilitate the delivery of chemotherapy in cancer treatment. However, the process typically uses nonspecific microbubbles, leading to low tumor-to-normal tissue uptake ratio and adverse side effects. In this study, we synthesized the LHRH receptor-targeted and paclitaxel (PTX)-loaded lipid microbubbles (TPLMBs) for tumor-specific binding and enhanced therapeutic effect at the tumor site. An ovarian cancer xenograft model was established by injecting A2780/DDP cells intraperitoneally in BALB/c nude mice. Microscopic imaging of tumor sections after intraperitoneal injection of TPLMBs showed effective binding of the microbubbles with cancer cells. Ultrasound mediated destruction of the intraperitoneally injected TPLMBs yielded a superior therapeutic outcome in comparison with other treatment options. Immunohistochemical analyses of the dissected tumor tissue further confirmed the increased tumor apoptosis and reduced angiogenesis. Our experiment suggests that ultrasound-mediated intraperitoneal administration of the targeted drug-loaded microbubbles may be a useful method for the treatment of ovarian cancer. PMID- 24237051 TI - Oil-isolated hydrogel microstructures for sensitive bioassays on-chip. AB - Multiplexed, sensitive, and on-chip molecular diagnostic assays are essential in both clinical and research settings. In past work, running reactions in nanoliter to femtoliter-sized volumes such as microwells or droplets has led to significant increases in detection sensitivities. At the same time, hydrogels have emerged as attractive scaffolds for bioassays due to their nonfouling, flexible, and aqueous properties. In this paper, we combine these concepts and develop a novel platform in which hydrogel compartments are used as individually confined reaction volumes within a fluorinated oil phase. We fabricate functional and versatile hydrogel microstructures in microfluidic channels that are physically isolated from each other using a surfactant-free fluorinated oil phase, generating picoliter- to nanoliter-sized immobilized aqueous reaction compartments that are readily functionalized with biomolecules. In doing so, we achieve monodisperse reaction volumes with an aqueous interior while exploiting the unique chemistry of a hydrogel, which provides a solid and porous binding scaffold for biomolecules and is impenetrable to oil. Furthermore, our lithographically defined reaction volumes are readily customized with respect to geometry and chemistry within the same channel, allowing rational tuning of the confined reaction volume on a post-to-post basis without needing to use surfactants to maintain stability. We design and implement a multiplexed signal amplification assay in which gel-bound enzymes turn over small molecule substrate into fluorescent product in the oil-confined gel compartment, providing significant signal enhancement. Using short (20 min) amplification times, the encapsulation scheme provides up to 2 orders of magnitude boost of signal in nucleic acid detection assays relative to direct labeling and does not suffer from any cross-talk between the posts. We ultimately demonstrate up to 57-fold increase in nucleic acid detection sensitivity compared to a direct labeling scheme. PMID- 24237052 TI - Impaired hepatic and intestinal ATP-binding cassette transporter G5/8 was associated with high exposure of beta-sitosterol and the potential risks to blood brain barrier integrity in diabetic rats. AB - OBJECTIVES: Plant sterols are thought to treat hypercholesterolemia via inhibiting intestinal cholesterol absorption. The aim of this study was to evaluate the contribution of impaired ATP-binding cassette transporter G5/8 (ABCG5/8) expression by diabetes to the increased beta-sitosterol (BS) exposure and impact of increased BS on integrity of blood-brain barrier (BBB). METHODS: Basal BS level in tissues of streptozotocin-inducted rats and ABCG5/8 protein levels in liver and intestine were investigated; pharmacokinetics of BS was studied following oral dose; and primarily cultured rat brain microvessel endothelial cells (rBMECs) were used to study BS transportation across BBB and effect of BS on BBB integrity. KEY FINDINGS: Diabetic rats showed greatly upgraded basal levels of BS in plasma, intestine, cerebral and hippocampus, accompanied by impairment of ABCG5/8 protein expression in liver and intestine. Pharmacokinetics studies demonstrated higher AUC0-48 and Cmax , and lower faecal recoveries of BS after oral administration, indicating enhancement of absorption or efflux impairment. In-vitro data showed increased ratio of BS/cholesterol in high levels BS-treated rBMECs was associated with increased BBB permeability of some biomarkers including BS itself. CONCLUSIONS: Impaired ABCG5/8 protein expression by diabetes led to increase in BS exposure, which may be harmful to BBB function. PMID- 24237054 TI - Better protection for patentees: preliminary injunctions in the EU for pharmaceutical patent matters. PMID- 24237053 TI - Beta-lactam hypersensitivity in children with cystic fibrosis: a study in a specialized pediatric center for cystic fibrosis and drug allergy. AB - BACKGROUND: Beta-lactam hypersensitivity (HS) is suspected in 5-12% of the children, but proven in only 10-15% of those children, based on skin and challenge tests results. In contrast, 30-60% of patients with cystic fibrosis (CF) are diagnosed allergic to beta-lactams, based mainly on the clinical history of the patients. OBJECTIVES: To confirm or rule out a suspected beta-lactam HS in CF children and to determine the prevalences of suspected and confirmed beta lactam HS in those children. PATIENTS AND METHODS: Children with CF and suspected beta-lactam HS were explored by means of skin and challenge tests with the suspected and alternate beta-lactams. The results in CF children were compared with those reported in the literature in non- CF children. RESULTS: Eight of the 701 CF children followed in our center between 1990 and 2011 (1.14%), and 11 other children from other centers were explored for suspected beta-lactam HS. Beta-lactam HS was diagnosed in nine of these children (47.3%). Based on the results in the children followed in our center, the prevalence of beta-lactam HS was 0.71% (5/701) in CF children vs. a mean estimated prevalence of 1-1.5% in the general pediatric population. CONCLUSION: Our results contrast with those of most previous studies. Although half of the CF children with suspected beta-lactam HS were truly allergic to beta-lactams, the general prevalence of beta-lactam HS in CF children was very low. This may result from tolerance induced by frequent and/or prolonged treatments with beta-lactams. PMID- 24237055 TI - Different rules, different results: patent litigation after In re Baxter. PMID- 24237056 TI - Supreme Court of India rejects Novartis' cancer drug patent. PMID- 24237059 TI - Legitimate patent extension or patent system abuse? AB - This article examines strategies used by innovators in the pharmaceutical industry in order to extend the legal monopolies available to them in order to prevent generic sales of their products for as long as possible. We examine patent procurement strategies in which secondary patents are filed for developments relating to a specific active ingredient. Another strategy adopted by innovators has involved the registration and de-registration of particular drug formulations in order to influence the relevant dates for calculating both patent term extensions and also the term of regulatory data exclusivity. We conclude that, in all cases, while the letter of the law has been complied with, in certain cases, readers may conclude that the spirit of the law has not been complied with. We expect that over the next 5-10 years, patent granting authorities and national courts will increasingly scrutinize these types of activities in order to ensure ethical behavior on the part of all stakeholders. PMID- 24237060 TI - Challenges to obtaining good pharmaceutical patents in Japan: 2009 and beyond. AB - The Japanese patent practice does not allow patents for medical activities as such, but only protects product inventions relating to pharmaceutical subject matter. However, recently, the Japanese Examination Guidelines have been amended to protect inventions, in which patentable features are only found in administration/dosage, thereby substantially protecting medical activities. In this review article, the revised Examination Guidelines are reviewed and explained from various aspects of view. Enablement/written description (support) requirements, which are important factors in obtaining reasonable patent scope of coverage, are further reviewed in terms of comparison among trilateral offices (USPTO, EPO and Japanese Patent Office). Recent court decisions are also reviewed for creating proper IP strategies in the field of pharmaceutical inventions. PMID- 24237061 TI - Current trends in the development of wound dressings, biomaterials and devices. AB - Wound management covers all aspects of patient care from initial injury, treatment of infection, fluid loss, tissue regeneration, wound closure to final scar formation and remodeling. There are many wound-care products available including simple protective layers, hydrogels, metal ion-impregnated dressings and artificial skin substitutes, which facilitate surface closure. This review examines recent developments in wound dressings, biomaterials and devices. Particular attention is focused on the design and manufacture of hydrogel-based dressings, their polymeric constituents and chemical modification. Finally, topical negative pressure and hyperbaric oxygen therapy are considered. Current wound-management strategies can be expensive, time consuming and labor intensive. Progress in the multidisciplinary arena of wound care will address these issues and be of immense benefit to patients, by improving both clinical outcomes and their quality of life. PMID- 24237063 TI - Newer glucocorticosteroids and corticosteroid resistance reversal in asthma. AB - Inflammation is the hallmark of asthma. Glucocorticosteroids inhibit this inflammation and are the mainstay of therapy in asthma, however, they suffer from their own drawbacks. They possess high potency but their continued use has a negative influence on health. Hence, quest for a steroid with good potency but without the undesirable effects is ongoing. Besides, steroid resistance is a problem in a substantial proportion of severe asthmatics. Deeper insight into the molecular mechanism of this refractoriness has led to the successful trial of certain drugs to overcome this problem. This review attempts to discuss some of the patents related to improved glucocorticoids and those agents that have the potential to restore steroid sensitivity in severe asthmatics. PMID- 24237062 TI - New immunological approaches in treating and diagnosing CNS diseases. AB - The immune system evolved to launch effective and specific responses against pathogens. A key feature of this defense mechanism is its ability to differentiate between self and nonself. However, in autoimmune diseases, the host's immune system fails to discriminate self versus foreign. The CNS is further protected by the blood-brain barrier. In spite of its 'immune privilege,' the brain is not protected from autoimmunity; perhaps paradoxically xenoantibodies can be used to treat neurological diseases. We describe patents covering treatment methods for CNS diseases with suspected or demonstrated autoimmune etiology. These include multiple sclerosis and, Alzheimer's and Parkinson's disease. The goal is to less invasively, yet efficiently, treat neurological diseases. Although autoimmune responses are often detrimental, recent studies have begun to harness, boost and induce immune responses as a mechanism of treatment. The patents discussed herein highlight new treatments for Alzheimer's and Parkinson's disease, multiple sclerosis, and seizure disorders. PMID- 24237064 TI - Prostaglandin EP4 antagonists. AB - Prostaglandin antagonists, with their pharmacological effects, are well-known drugs capable of treating widely diffused illnesses, including pain and inflammation disorders. In recent years, a major research focus has been devoted to the identification of agents able to selectively antagonize each receptor with which prostaglandins interact. This review attempts to give a broad overview of molecules capable of selectively blocking the prostaglandin PGE2 EP4 receptor. Further therapeutic applications and uses have also been disccussed, including the first drug candidate to have reached clinical trials within the last few years. PMID- 24237065 TI - The central question of type 2 diabetes. AB - Type 2 diabetes (T2D) represents a significant global epidemic with more than 285 million people affected worldwide. Regulating glycemia in T2D patients can be partially achieved with currently available treatment, but intensive research during the last decades have led to the discovery of modified compounds or new targets that could represent great hope for safe and effective treatment in the future. Among them, targets in the CNS that are known to control feeding and body weight have been also shown to exert glucoregulatory actions, and could be a key in the development of a new generation of drugs in the field of T2D. Such drugs would be of great interest since they can be used both in the treatment of diabetes and obesity. This patent review aims to establish an overview of recent patents disclosing new therapeutic opportunities targeting peripheral, as well as central targets for the treatment of T2D. PMID- 24237068 TI - The usefulness of plasma histamine and different tryptase cut-off points in the diagnosis of peranaesthetic hypersensitivity reactions. AB - Anaesthetic hypersensitivity reactions can be IgE- or not IgE-mediated and are a challenge to find the causal agent. Histamine and tryptase determination are classically considered useful in the diagnosis of these reactions. The aim of our study was to assess the diagnostic usefulness of plasma histamine and different cut-off points of serum tryptase. METHODS: Patients suffering a reaction suggestive of hypersensitivity during general anaesthesia in Clinica Universidad de Navarra (2008-2012) were included. Serum tryptase and plasma histamine were measured at the time of the reaction and 2 h later. Baseline tryptase was also determined. Four to eight weeks after the reaction an allergological study was performed to all the drugs or products involved in the reaction. RESULTS: Sixty five patients suffered an immediate hypersensitivity reaction during the period of the study. Thirty-seven patients (20 male) with median age 48 years (12-79) were included because they completed allergological study, and histamine and tryptase were correctly obtained. Elevated plasma histamine was observed in 34 cases (92%). Tryptase exceeded twice the basal values in 10 patients (31%). Using different cut-off points of tryptase, the number of patients with elevated tryptase would be 15 patients (41%) for a cut-off point of 5 MUg/L; 12 patients (32%) for a cut-off point of 8.23 MUg/L; nine patients (24%) for 10.5 MUg/L; and eight patients (22%) for 11.4 MUg/L. The median tryptase level for the IgE mediated reactions was 9.0 MUg/L (2-70 MUg/L) and 4.0 MUg/L (3-13 MUg/L) in non IgE-mediated reactions (P < 0.01). Median tryptase levels were higher in more severe reactions (grade 2 or 3) in comparison with grade 1. The best ratio for serum-tryptase-during-reaction/basal-serum-tryptase to discriminate between IgE and non-IgE reactions was 2.0. CONCLUSION: The best criterion for discriminating IgE- and non IgE-mediated hypersensitivity reactions in anaesthesia was a tryptase value exceeding twice the basal one. PMID- 24237069 TI - Proposal for establishment of the UK Cranial Reconstruction Registry (UKCRR). AB - BACKGROUND: The increasing utilisation of decompressive craniectomy for traumatic brain injury and stroke has led to an increase in the number of cranioplasties undertaken. Cranioplasty is also undertaken following excision of tumours originating from or invading the skull vault, removal of bone flaps due to post operative infection, and decompressive craniectomy for the management of rarer causes of brain oedema and/or refractory intracranial hypertension. The existing literature which mainly consists of single-centre, retrospective studies, shows a significant variation in practice patterns and a wide range of morbidity. There also exists a need to measure the outcome as perceived by the patients themselves with patient reported outcome measures (PROMs; functional outcome, quality of life, satisfaction with cosmesis). In the UK, the concept of long-term surveillance of neurosurgical implants is well established with the UK shunt registry. Based on this background, we propose to establish the UK Cranial Reconstruction Registry (UKCRR). AIM: The overarching aim of the UKCRR is to collect high-quality data about cranioplasties undertaken across the UK and Ireland in order to improve outcomes for patients. METHODS: Any patient undergoing reconstruction of the skull vault with autologous bone, titanium, or synthetic material in participating units will be eligible for inclusion. Data will be submitted directly by participating units to the Outcome Registry Intervention and Operation Network secure platform. A Steering Committee will be responsible for overseeing the strategic direction and running of the UKCRR. OUTCOME MEASURES: These will include re-operation due to a cranioplasty-related issue, surgical site infection, re-admission due to a cranioplasty-related issue, unplanned post-operative escalation of care, adverse events, length of stay in admitting unit, destination at discharge from admitting unit, mortality at discharge from admitting unit, neurological status and PROMs during routine follow-up. CONCLUSION: The UKCRR will be an important pillar in the ongoing efforts to optimise the outcomes of patients undergoing cranioplasty. PMID- 24237070 TI - Efficacy and safety of telaprevir and boceprevir in patients with hepatitis C genotype 1: a meta-analysis. AB - WHAT IS KNOWN AND OBJECTIVE: Two NS3/4A protease inhibitors (PIs), telaprevir and boceprevir, were recently approved in the United States. The primary objective was to compare the efficacy and safety of triple therapies including either PI to dual therapy in patients with chronic hepatitis C genotype 1; the secondary objective was to conduct subgroup analyses to make comparisons based on patients' race. METHODS: Published and unpublished RCTs were selected if they: (i) had patients with chronic hepatitis C genotype 1, (ii) compared triple therapies (telaprevir or boceprevir + peg-interferon + ribavirin) and dual therapy (peg interferon + ribavirin) and (iii) measured the outcome using sustained virologic response (SVR). RESULTS: A total of 4421 patients from 10 evaluated articles were included in the meta-analysis. Overall, triple therapy was significantly associated with a higher achievement of SVR than dual therapy: (i) telaprevir based triple therapy in treatment-naive patients (relative risk [RR] = 1.62; 95% confidence interval [CI], 1.47-1.78), (ii) telaprevir-based triple therapy in treatment-experienced patients (RR = 3.85; 95% CI, 3.03-4.90), (iii) boceprevir based triple therapy in treatment-naive patients (PR = 1.70; 95% CI, 1.56-1.86) and (iv) boceprevir-based triple therapy in treatment-experienced patients (RR = 2.98; 95% CI, 2.29-3.87). Although black and non-black patients demonstrated the higher rates of achieving SVR with triple therapy compared to dual therapy, the rates of SVR were still lower among black patients than among non-black patients. Patients on triple therapies had the significantly increased incidences of treatment discontinuation attributable to adverse events and serious adverse events when compared to dual therapy, especially treatment-experienced patients. WHAT IS NEW AND CONCLUSIONS: Regarding achieving SVR, triple therapies including either PI are superior to dual therapy for both treatment-naive and treatment experienced patients. PMID- 24237071 TI - Proteomic studies related to genetic determinants of variability in protein concentrations. AB - Genetic variation has multiple effects on the proteome. It may influence the expression level of proteins, modify their sequences through single nucleotide polymorphisms, the occurrence of allelic variants, or alternative splicing (ASP) events. This perspective paper summarizes the major effects of genetic variability on protein expression and isoforms and provides an overview of proteomics techniques and methods that allow studying the effects of genetic variability at different levels of the proteome. The paper provides an overview of recent quantitative trait loci studies performed to explore the effect of genetic variation on protein expression (pQTL). Finally it gives a perspective view on advances in proteomics technology and the role of the Chromosome-Centric Human Proteome Project (C-HPP) by creating large-scale resources that may facilitate performing more comprehensive pQTL experiments in the future. PMID- 24237073 TI - Immunohistochemical characterization of novel murine monoclonal antibodies against human placenta-specific 1. AB - Human PLAC1 (placenta-specific 1) is a new member of cancer-testis antigens with 212 amino acids, and its expression is restricted to placenta and at much lower levels to testis. Recently, ectopic expression of the PLAC1 transcript has been demonstrated in a wide range of human tumors and cancer cell lines with a proposed function in tumor cell growth. No monoclonal anti-PLAC1 antibody applicable to immunohis-tochemical staining is available so far. To better understand the PLAC1 expression and localization, we aimed to produce monoclonal antibodies (mAbs) against the extracellular region of PLAC1. Mice were immunized with a synthetic peptide corresponding to the C-terminal 11 amino acids of PLAC1 conjugated with a carrier protein. Hybridomas were produced by standard protocol and screened for positive reactivity by enzyme-linked immunosorbent assay. Reactivity of final two clones was then assessed by Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). Both clones showed a specific immunostaining pattern in human term placenta as the positive control. Reactivity was mostly localized to the cytoplasm of syncytiotrophoblasts. One of the clones showed an excellent staining signal in breast, ovary, and prostate cancer cell lines. Importantly, no reactivity was observed with human lymph node cells or prostate. None of the mAbs were able to detect PLAC1 in Western blot. Based on the present results, these mAbs can be used for detection of PLAC1 in IHC and ICC techniques. PMID- 24237074 TI - Take your time. PMID- 24237075 TI - Lung cancer: let's try for prevention and cure. PMID- 24237076 TI - Vitamin D and tuberculosis. PMID- 24237079 TI - The utility of genetics in inherited cancer. PMID- 24237080 TI - The Angelina Jolie effect. PMID- 24237081 TI - Vitamin D and tuberculosis: hope or hype? PMID- 24237082 TI - Pathways to enhancing the quality of stroke care through national data monitoring systems for hospitals. PMID- 24237083 TI - Immigration screening for latent tuberculosis infection. PMID- 24237084 TI - Immigration screening for latent tuberculosis infection. PMID- 24237085 TI - Think before you insert an intravenous catheter. PMID- 24237086 TI - Epidemiology of tuberculosis and levels of vitamin D in Australia: person, place and time. PMID- 24237087 TI - Liaise with pathologists to refine understanding of the prostate-specific antigen test. PMID- 24237088 TI - Re-treating bleeding hereditary haemorrhagic telangiectasia with bevacizumab. PMID- 24237089 TI - Sotalol-associated cardiogenic shock in a patient with asymptomatic transient rate-related cardiomyopathy. PMID- 24237090 TI - Amanita phalloides poisoning and treatment with silibinin in the Australian Capital Territory and New South Wales. PMID- 24237091 TI - Reinforcing the iodine message for pregnant women in Australia. PMID- 24237092 TI - Psychotropic medication in pregnancy. PMID- 24237093 TI - Dealing with disclosure in patients with borderline personality traits. PMID- 24237095 TI - Difficult but necessary conversations--the case for advance care planning. AB - Many patients at the end of life receive care that is inappropriate or futile and, if given the opportunity to discuss their care preferences well ahead of death, may well have chosen to forgo such care. Advance care planning (ACP) is a process of making decisions about future health care for patients in consultation with clinicians, family members and important others, and to safeguard such decisions if patients were to lose decisional capacity. Although ACP has existed as an idea for decades, acceptance and operationalisation of ACP within routine practice has been slow, despite evidence of its benefits. The chief barriers have been social and personal taboos about discussing the dying process, avoidance by medical professionals of responsibility for initiating, coordinating and documenting discussions about ACP, absence of robust and standardised procedures for recording and retrieving ACP documents across multiple care settings, and legal and ethical concerns about the validity of such documents. For ACP to become part of mainstream patient-centred care, accountable clinicians working in primary care, hospitals and nursing homes must effectively educate colleagues and patients about the purpose and mechanics of ACP, mandate ACP for all eligible patients, document ACP in accessible formats that enable patient wishes to accurately guide clinical management, devise methods for reviewing ACP decisions when clinically appropriate, and evaluate congruence between expressed patient wishes and actual care received. Public awareness campaigns coupled with implementation of ACP programs sponsored by collaborations between hospital and health services, Medicare locals and residential care facilities will be needed in making system-wide ACP a reality. PMID- 24237096 TI - Preoperative cardiac evaluation and management of patients undergoing elective non-cardiac surgery. AB - Perioperative cardiac complications are a common cause of death and major morbidity in patients undergoing non-cardiac surgery. Preoperative evaluation and medical optimisation can improve outcomes, although the evidence base is limited. Evidence of effectiveness is strongest for prophylactic use of beta-blockers in high-risk patients and aspirin in patients with coronary artery disease. Particular challenges arise among patients with heart failure or valvular heart disease or those receiving antithrombotic therapy for coronary artery stents or atrial fibrillation. Close liaison between general practitioners, surgeons, anaesthetists and cardiologists is needed for optimising preoperative management and subsequent clinical outcomes in high-risk patients. PMID- 24237097 TI - Lung cancer in Victoria: are we making progress? AB - OBJECTIVES: To identify areas to improve patient management in lung cancer, which remains the greatest cause of death from cancer in Australia. DESIGN AND SETTING: Retrospective survey of all cases of lung cancer reported to the Victorian Cancer Registry from 1 January to 30 June 2003 and followed up for 5 years. MAIN OUTCOME MEASURES: Patient and disease characteristics, investigations, staging, treatment, cause of death, survival. RESULTS: 841 patients were included. Smoking data were available for 799, of whom 63 (7.9%) had never smoked. Of 655 non-small cell lung cancer (NSCLC) cases, 198 (30.2%) were treated with curative intent, 125 (19.1%) by surgery and 73 (11.1%) by radiotherapy with or without chemotherapy. Only 7 (6.9%) of surgical patients with complete R0 resection had adjuvant chemotherapy. Of 101 small cell lung cancer (SCLC) cases, a third had limited stage disease which was mostly treated with curative intent by chemotherapy with or without radiotherapy. Patients whose cases were discussed at a multidisciplinary meeting (MDM) were significantly more likely to receive anticancer treatment and had longer survival; on multivariate analysis, MDM discussion was an independent prognostic factor. Compared with a similar survey 10 years earlier, the median age of patients diagnosed with lung cancer had increased by almost 3 years, the proportion of affected men decreased and adenocarcinoma was more frequent, while 10% of patients continued to have no pathologically confirmed diagnosis and 26% continued to receive no anticancer treatment. The number of patients with NSCLC who went on to a definitive surgical procedure fell with no detriment to survival, which likely reflected better staging with the introduction of positron emission tomography scanning. CONCLUSIONS: Opportunities to improve patient management included increasing the proportion with a pathologically confirmed diagnosis and greater use of postsurgical adjuvant chemotherapy. A high proportion of patients received no treatment, with underuse of chemotherapy and radiotherapy. Critically, the low rate of case discussions at MDMs needs to increase. However, effective strategies are required to identify cases early, as over two-thirds currently present with incurable disease. PMID- 24237098 TI - Preventing breast and ovarian cancers in high-risk BRCA1 and BRCA2 mutation carriers. AB - OBJECTIVE: To estimate the prevalence of the use of cancer risk-reducing measures among Australian BRCA1 and BRCA2 mutation carriers. DESIGN, SETTING AND PARTICIPANTS: Prospective follow-up of female carriers of BRCA1 or BRCA2 mutations who had no personal history of cancer and were enrolled in a multiple case breast cancer family cohort study (kConFab). Data, including cancer events and uptake of risk-reducing surgery and medication were collected by self-report at cohort entry and 3 yearly thereafter. Surgery was confirmed from pathology and medical records. Women were followed up from enrolment until cancer diagnosis, date of last follow-up, or death. Data were collected from 3 November 1997 to 21 May 2012. MAIN OUTCOME MEASURES: Uptake of risk-reducing surgery and/or medication. RESULTS: Of 175 BRCA1 and 150 BRCA2 mutation carriers (median age, 37 years at cohort enrolment), 69 (21%) underwent risk-reducing mastectomy, 125 (38%) underwent risk-reducing bilateral salpingo-oophorectomy and nine (3%) participated in a clinical trial of risk-reducing medication, during 2447 person years of follow-up (median follow-up, 9 years). Sixty-eight women (21%) reported incident cancers, including 52 breast cancers and nine ovarian cancers (defined in this article as high-grade serous cancers of the ovary, fallopian tube or peritoneum). CONCLUSIONS: There is considerable scope to increase the uptake of cancer risk-reducing measures in Australian BRCA1 and BRCA2 mutation carriers. These findings should drive (i) future research into the factors contributing to low uptake in Australia and (ii) changes to policy and practice to help better translate genetic knowledge into reductions in cancer incidence. PMID- 24237099 TI - Low awareness of adverse drug reaction reporting systems: a consumer survey. AB - OBJECTIVE: To determine levels of public awareness of consumer adverse drug reaction (ADR) reporting systems in Australia. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study conducted in 2012 of residents of the Hunter Valley region of New South Wales, who participated in a computer-assisted telephone interview (CATI), and a national sample, who completed an online Pureprofile survey. MAIN OUTCOME MEASURES: Proportion of respondents experiencing ADRs; the type of medicine involved; whether participants reported the adverse event and to whom; awareness and use of existing consumer ADR reporting mechanisms. RESULTS: There were 2484 CATI respondents and 2497 Pureprofile respondents. Side effects with medicines were very common (46.3% of respondents), most relating to prescription medicines (88.4%). Among respondents who had experienced a side effect, 84.6% reported the event to a health care professional, most often a general practitioner. Awareness of consumer ADR reporting schemes was low (10.4%). Of 217 respondents who had experienced a side effect and were aware of consumer reporting schemes, 46 (21.2%) had reported an ADR using one of these schemes. CONCLUSIONS: Consumers can contribute to our understanding of medicines safety, but there is low awareness of available reporting systems. Some consumers aware of ADR self-reporting systems appear prepared to use them, but promotion of and education on how to use reporting systems are required. Significant resources may be needed to support an enhanced consumer reporting scheme. PMID- 24237100 TI - Chiropractic Observation and Analysis Study (COAST): providing an understanding of current chiropractic practice. AB - OBJECTIVES: COAST (Chiropractic Observation and Analysis Study) aimed to describe the clinical practices of chiropractors in Victoria, Australia. DESIGN: Cross sectional study using the BEACH (Bettering the Evaluation and Care of Health) methods for general practice. SETTING AND PARTICIPANTS: 180 chiropractors in active clinical practice in Victoria were randomly selected from the list of 1298 chiropractors registered on Chiropractors Registration Board of Victoria. Twenty four chiropractors were ineligible, 72 agreed to participate, and 52 completed the study. MAIN OUTCOME MEASURES: Each participating chiropractor documented encounters with up to 100 consecutive patients. For each chiropractor-patient encounter, information collected included patient health profile, patient reasons for encounter, problems and diagnoses, and chiropractic care. RESULTS: Data were collected on 4464 chiropractor-patient encounters from 52 chiropractors between 11 December 2010 and 28 September 2012. In most (71%) encounters, patients were aged 25-64 years; 1% of encounters were with infants (age < 1 year; 95% CI, 0.3% 3.2%). Musculoskeletal reasons for encounter were described by patients at a rate of 60 per 100 encounters (95% CI, 54-67 encounters) and maintenance and wellness or check-up reasons were described at a rate of 39 per 100 encounters (95% CI, 33 47 encounters). Back problems were managed at a rate of 62 per 100 encounters (95% CI, 55-71 encounters). The most frequent care provided by the chiropractors was spinal manipulative therapy and massage. CONCLUSIONS: A range of conditions are managed by chiropractors in Victoria, Australia, but most commonly these conditions are musculoskeletal-related. These results can be used by stakeholders of the chiropractic profession in workforce development, education and health care policy. PMID- 24237101 TI - Antimicrobial stewardship in Victorian hospitals: a statewide survey to identify current gaps. AB - OBJECTIVE: To determine antimicrobial stewardship (AMS) activities currently being undertaken at Victorian hospitals, identifying gaps when assessed against the Australian Commission on Safety and Quality in Health Care criteria for effective AMS. DESIGN, SETTING AND PARTICIPANTS: A survey open to all Victorian health services, conducted between January and March 2012. MAIN OUTCOME MEASURES: Availability of the endorsed prescribing guidelines, antimicrobial prescribing policies, formularies, approval systems for restricted antimicrobials, procedures for postprescription review, auditing and selective reporting of sensitivities. RESULTS: Response rates were 96.4% for public health services and 67.7% for private hospitals. Guidelines were available at all public and 88.1% of private hospitals, and 90.6% of public metropolitan, 45.7% of public regional and 21.4% of private hospitals had antimicrobial prescribing policies. Antimicrobial approval systems were used in 93.8% of public metropolitan, 17.3% of public regional and 4.8% of private hospitals. Prescribing audits were conducted by 62.5% of public metropolitan, 35.8% public regional and 52.4% of private hospitals. Nearly all hospitals had selective laboratory reporting of antimicrobial sensitivities. Few hospitals had dedicated funding for AMS personnel. CONCLUSIONS: We identified wide differences between hospital AMS activities. Additional support for AMS is particularly required in the public regional and private hospital sectors, principally in the key areas of policy development, antimicrobial approval systems, prescription review and auditing. Further research is required to develop recommendations for implementation of AMS within the regional and private hospital settings. PMID- 24237103 TI - A budding surprise from the joint. PMID- 24237102 TI - The sources of pharmaceuticals for problematic users of benzodiazepines and prescription opioids. AB - OBJECTIVES: To describe benzodiazepine and prescription opioid use by clients of drug treatment services and the sources of pharmaceuticals they use. DESIGN: Structured face-to-face interviews on unsanctioned use of benzodiazepines and prescription opioids were conducted between January and July 2008. PARTICIPANTS: Convenience sample of treatment entrants who reported regular (an average of >= 4 days per week) and unsanctioned use of benzodiazepines and/or prescription opioids over the 4 weeks before treatment entry. SETTING: Drug treatment services in Victoria, Queensland, Western Australia and Tasmania. MAIN OUTCOME MEASURES: Participant demographics, characteristics of recent substance use, substance use trajectories, and sources of pharmaceuticals. RESULTS: Two hundred and four treatment entrants were interviewed. Prescription opioids were predominantly obtained from non-prescribed sources (78%, 84/108). In contrast, medical practitioners were the main source for benzodiazepines (78%, 113/144). Forging of prescriptions was extremely uncommon. A mean duration of 6.3 years (SD, 6.6 years) for benzodiazepines and 4.4 years (SD, 5.7 years) for prescription opioids was reported between first use and problematic use--a substantial window for intervention. CONCLUSIONS: Medical practitioners are an important source of misused pharmaceuticals, but they are not the main source of prescription opioids. This has implications for prescription drug monitoring in Australia: current plans (to monitor only Schedule 8 benzodiazepines and prescription opioids) may have limited effects on prescription opioid users who use non prescribed sources, and the omission of most benzodiazepines from monitoring programs may represent a lost opportunity for reducing unsanctioned use of benzodiazepines and associated harm. PMID- 24237104 TI - Are global health leaders effectively strengthening local public health systems? PMID- 24237105 TI - A difficult conversation. PMID- 24237108 TI - Finding our way through the maze. PMID- 24237109 TI - Comparative phenotypic and genotypic characterization of temporally related nontyphoidal Salmonella isolated from human clinical cases, pigs, and the environment in North Carolina. AB - Nontyphoidal Salmonella infections caused by antimicrobial-resistant (AMR) strains are of great public health concern. We compared the phenotypic and genotypic relationships among temporally and spatially related AMR Salmonella isolates (n=1058) representing several predominant serovars, including Salmonella Typhimurium, Salmonella Typhimurium var. 5-, Salmonella Derby, Salmonella Heidelberg, Salmonella Muenchen, Salmonella Schwarzengrund, and Salmonella Rissen of human clinical cases (n=572), pig (n=212), and farm environment (n=274) origin in North Carolina. Antimicrobial susceptibility testing was performed using the broth microdilution method, and genotypic resistance determinants, including class I and II integrons, were identified. Overall, Salmonella isolates exhibited the highest frequency of resistance to tetracycline (50%), followed by sulfisoxazole (36%) and streptomycin (27%). We identified 16 different antimicrobial resistance genes, including extended spectrum and AmpC beta lactamases-producing genes (bla(TEM), bla(PSE), and bla(CMY-2)), in all the beta lactam- and cephalosporin-resistant Salmonella isolates from humans, pigs, and the environment. Class I integrons of 1-kb and 1.2-kb size were identified from all the three sources (humans, 66%; pigs, 85%; environment, 58%), while Class II integrons of 2-kb size were identified only in pig (10%) and environmental (19%) isolates. We detected genotypic similarity between Salmonella Typhimurium isolated from humans, pigs, and the environment while serovars Derby, Heidelberg, and Muenchen exhibited genotypic diversity. Detection of AMR Salmonella isolates from humans, pigs, and the environment is a concern for clinicians and veterinarians to mitigate the dissemination of AMR Salmonella strains. PMID- 24237111 TI - Learning Need of Chinese Patients before Undergoing Elective Percutaneous Coronary Intervention. AB - Abstract This study aimed to determine the learning needs of Chinese patients going for elective percutaneous coronary intervention (PCI) in order to design nurse led education programs. A self-administered survey was completed by a total of 395 patients prior to the procedure. Face-to-face communication was chosen by 343 (86.8%) patients as the most preferred way of education. Doctor-in-charge was ranked as the most wanted educator by 372 (94.2%) patients, including 191 (45.4%) patients who chose both doctor-in-charge and nurse-in-charge. Interventional cardiologist was preferred by patients with higher education more than those with lower education (63.6% vs. 48.1%, p<0.05). Learning items such as self-rescue on heart attack, efficiency of PCI and post-procedural medication were regarded as the most important, which could be affected by age, gender and educational level. These findings would help to develop patient preferred programs that involve brief communications with doctors and more structured education activities led by nurses. PMID- 24237110 TI - Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9. AB - Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34(+) pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon-alpha or interleukin-12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR-7 and TLR-9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR-7 or TLR-9. PMID- 24237112 TI - Do provider service networks result in lower expenditures compared with HMOs or primary care case management in Florida's Medicaid program? AB - OBJECTIVE: To determine the impact of Florida's Medicaid Demonstration 4 years post-implementation on per member per month (PMPM) Medicaid expenditures and whether receiving care through HMOs versus provider service networks (PSNs) in the Demonstration was associated with PMPM expenditures. DATA: Florida Medicaid claims from two fiscal years prior to implementation of the Demonstration (FY0405, FY0506) and the first four fiscal years after implementation (FY0607 FY0910) from two urban Demonstration counties and two urban non-Demonstration counties. STUDY DESIGN: A difference-in-difference approach was used to compare changes in enrollee expenditures before and after implementation of the Demonstration overall and specifically for HMOs and PSNs. DATA EXTRACTION: Claims data were extracted for enrollees in the Demonstration and non-Demonstration counties and collapsed into monthly amounts (N = 26,819,987 person-months). PRINCIPAL FINDINGS: Among SSI enrollees, the Demonstration resulted in lower increases in PMPM expenditures over time ($40) compared with the non Demonstration counties ($186), with Demonstration PSNs lowering PMPM expenditures by $7 more than HMOs. Savings were also seen among TANF enrollees but to a lesser extent. CONCLUSIONS: The Medicaid Demonstration in Florida appears to result in lower PMPM expenditures. Demonstration PSNs generated slightly greater reductions in expenditures compared to Demonstration HMOs. PSNs appear to be a promising model for delivering care to Medicaid enrollees. PMID- 24237113 TI - Early trajectory of psychiatric symptoms after traumatic brain injury: relationship to patient and injury characteristics. AB - Psychiatric disturbance is common and disabling after traumatic brain injury (TBI). Few studies have investigated the trajectory of psychiatric symptoms in the first 6 months postinjury, when monitoring and early treatment might prevent persistent difficulties. The aim of this study was to examine the trajectory of psychiatric symptoms 1-6 months post-TBI, the patient/injury characteristics associated with changes, and characteristics predictive of persisting symptoms. A secondary analysis was performed on data from a clinical trial with three data collection points. Across eight centers, 872 participants with complicated mild to severe TBI were administered the Brief Symptom Inventory (BSI) at 30, 90, and 180 days postinjury. Mixed-effects models were used to assess longitudinal changes in the BSI Global Severity Index (GSI). Multi-variate logistic regression was used to assess predictors of clinically significant GSI elevations persisting to 6 months post-TBI. In general, GSI scores improved over time. Women improved faster than men; race/ethnicity was also significantly associated with rate of change, with Hispanics showing the most and African Americans the least improvement. Clinically significant psychiatric symptoms (caseness) occurred in 42% of the sample at 6 months, and more than one type of symptom was common. Significant predictors of caseness included African American race, age from 30 to 60 years, longer post-traumatic amnesia (PTA) duration, pre-TBI unemployment, and pre-TBI risky alcohol use. Findings indicate that psychiatric symptoms are common in the first 6 months post-TBI and frequently extend beyond the depression and anxiety symptoms that may be most commonly screened. Patients with longer PTA and preinjury alcohol misuse may need more intensive monitoring for symptom persistence. PMID- 24237114 TI - Recent advances in immunotherapy for allergic diseases. AB - Allergic diseases are a major health problem worldwide. The therapeutic approaches to treat allergic rhinitis (AR) and allergic asthma (AA) fall in three major categories. The first step is allergen avoidance, or reduction of exposure to the offending allergen(s). The second and most widely used therapeutic practice is the prescription of relevant medication to reduce symptoms. The third therapeutic element is specific allergy vaccination, also known as allergen specific immunotherapy. Allergen-specific immunotherapy (SIT) is the only etiologic treatment of allergic disorders that can alter the natural course of the disease. In this review, recent advances in immunotherapy and relevant patents are presented. General vaccine modifications could be applied for any type of allergen. New specific modifications in allergic vaccines have been developed for a variety of allergies such as house dust mites, horse, cat, parvalbumin and from birch, ragweed and parietaria pollen. PMID- 24237115 TI - Tuning the observability of surface plasmon in silica-gold raspberry shaped nanoparticles using cuprous oxide shell. AB - A raspberry shaped silica-gold nanoparticle system has been coated with a cuprous oxide shell using a simple wet chemical approach. The optical properties of such particles depend on thin dielectric shell material, and we calculate far-field scattering and extinction of cuprous oxide coated silica-gold composite. In accordance with our theoretical findings, for ultrasmall gold nanoparticles (AuNPs < 5 nm) attached over silica, the localized surface plasmon resonance (LSPR) peak is completely suppressed after Cu2O coating. The cloaking (nonobservability) of the LSPR peak in extinction spectra has been explained via calculation of contribution from absorbance (<10%) and scattering (>90%) in the composite nanostructure. For larger particles (>5 nm), the traditional red-shift of the plasmon peak (from 532 to 588 nm) is still significant due to the large dielectric constant (approx. 8.0 @ 600 nm) of cuprous oxide (Cu2O) coating. A complete and controlled suppression of LSPR in small sized gold nanoparticles due to high dielectric refractory oxide shell could play a significant role in plasmon derived applications. PMID- 24237116 TI - Determination of equine fetal sex by Doppler ultrasonography of the gonads. AB - REASONS FOR PERFORMING THE STUDY: The identification of fetal sex in horses by location of the genital tubercle between 55 and 70 days of pregnancy is hampered by the large amount of allantoic fluid, extensive fetal movements and the extremely long umbilical cord; however, reliable results have been achieved by ultrasonographic evaluation of the fetal gonads at 110-150 days of pregnancy. OBJECTIVES: The aim of this study was to diagnose the sex of equine fetuses using B-mode and/or colour Doppler transrectal ultrasonography in fetuses of different ages. STUDY DESIGN: Cross-sectional study comparing 2 methods of determining fetal sex. METHODS: The evaluations were performed in 86 mares at 90-180 days of pregnancy using transrectal B-mode and colour Doppler mode ultrasonography. Fetuses that had gonads with a homogeneous texture and a thin central longitudinal echogenic line were considered to be male. Females were identified by the presence of gonads with a central circular echogenic structure surrounded by a hypoechogenic external halo. RESULTS: Using B-mode ultrasonography, it was possible to determine the sex of 75% of the males, while determination of sex based on differences between the medullary and cortical layers of the ovary allowed 91.1% of females to be correctly identified. Using Doppler ultrasonography, 100% of males were successfully identified, while characteristic vascularisation of the female gonad could be detected in 98% of the evaluated female fetuses. CONCLUSIONS: Colour Doppler ultrasonography combined with B-mode ultrasonography allows the determination of fetal sex with greater accuracy than B-mode ultrasonography alone, particularly for the identification of the male gonad. The use of Doppler ultrasonography enables the identification of sex in older fetuses. PMID- 24237117 TI - Patentability of biologics in Canada: beyond patentable subject matter. PMID- 24237118 TI - Uncertainty regarding exemption from infringement for studies after approval, or not required, by the US FDA. PMID- 24237119 TI - Will the refusal of patent protection for Glivec(r) discourage future pharmaceutical innovation in India? PMID- 24237120 TI - University of Colorado licences out vaccine composition. PMID- 24237121 TI - Association of University Technology Managers Asia 2013 conference. AB - The Association of University Technology Managers is a nonprofit association of technology managers and business executives who manage IP. This year's Asian meeting was held in Japan for the first time. A number of participants and delegates not only from Asia but also from all over the world attended, and had a number of sessions dealing with R&D in universities, and IP derived from this. PMID- 24237124 TI - Post-Therasense inequitable conduct: a pharmaceutical perspective. AB - This article explores the policies behind and recent changes to the inequitable conduct defense in US patent law. Recognizing problems with the doctrine, the Federal Circuit clarified and heightened the underlying materiality and intent to deceive standards for inequitable conduct in its landmark Therasense decision in 2011. The doctrine underwent further reform later that year with the enactment of the America Invents Act, which, among other changes, created a supplemental examination mechanism by which a patentee can obtain PTO consideration of previously nondisclosed information and, subject to some limitations, inoculate itself from inequitable conduct challenges relating to the prior nondisclosure. This article discusses the present and future practical impact of these changes on patent litigation involving the pharmaceutical industry. PMID- 24237125 TI - Small-molecule inhibitors of IkappaB kinase (IKK) and IKK-related kinases. AB - The transcription factors NF-kappaB and IFN control important signaling cascades and mediate the expression of a number of important pro-inflammatory cytokines, adhesion molecules, growth factors and anti-apoptotic survival proteins. IkappaB kinase (IKK) and IKK-related kinases (IKKepsilon and TBK1) are key regulators of these biological pathways and, as such, modulators of these enzymes may be useful in the treatment of inflammatory diseases and cancer. We have reviewed the most recent IKK patent literature (2008-2012), added publications of interest overlooked in previous patent reviews and identified all the players involved in small-molecule inhibitors of the IKKs. This will provide the reader with a decisive summary of the IKK arena, a field that has reached maturity over a decade of research. PMID- 24237126 TI - Nanocoatings on implantable medical devices. AB - The global medical device industry has experienced significant growth over the past 5 years. The surge of patent publications in the field bears testimony to this fact. The advent of nanotechnology has opened up newer unexplored vistas in the field of medical devices. This review summarizes patents employing the principles of nanotechnology in the formulation of coatings for implantable medical devices. Patents selected have at least one entity or structure with dimensions in the nanometer range, which results in a therapeutic value addition. The strategies reviewed pertain to tackling issues such as restenosis and thrombosis in addition to improving the overall acceptability of the implantable medical device, particularly those placed in the vasculature. PMID- 24237127 TI - Recent patents and emerging therapeutics for HIV infections: a focus on protease inhibitors. AB - The inclusion of protease inhibitors (PIs) in highly active antiretroviral therapy has significantly improved clinical outcomes in HIV-1-infected patients. To date, PIs are considered to be the most important therapeutic agents for the treatment of HIV infections. Despite high anti-HIV-1 potency, poor oral bioavailability of PIs has been a major concern. For achieving therapeutic concentrations, large doses of PIs are administered, which results in unacceptable systemic toxicities. Such severe and long-term toxicities necessitate the development of safer and potentially promising PIs. Recently, considerable attention has been paid to the development of newer compounds capable of inhibiting wild-type and resistant HIV-1 protease. Some of these PIs have displayed potent HIV-1 protease inhibitory activity. In this review, we have made an attempt to provide an overview on clinically approved and newly developing PIs, and related recent patents in the development of novel PIs. PMID- 24237128 TI - Lipoidal soft hybrid biocarriers in pharmacotherapeutics. AB - The competition hike in the pharmaceutical market, the reduction in the fresh chemical-entity pipelines of pharmaceutical organization, the unwanted boost up in the cost for developing new chemical entities and the popularity of generics have all contributed to the effort to move ahead with newer drug-delivery systems that are aimed to provide optimized performance. Nanosized lipoidal soft hybrid biocarriers offer promise for safe, effective and targeted pharmacotherapeutics. The possibilities have risen by virtue of their ability of intracellular entry, biocompatible composition, precise control on drug release, targeted drug delivery, compatibility with a wide range of therapeutic compounds and flexibility in their routes of administration. Vesicles are lipoidal soft hybrid biocarrier-based membrane models developed to mimic the biological membrane, making them superior to other carriers by virtue of their biocompatibility and biodegradability. These features of vesicular carriers make them suitable for therapeutic as well as diagnostic applications. The aim of the present compilation is to briefly summarize the applications and developments in vesicular drug delivery through the patents issued in the past decade. PMID- 24237130 TI - Effect of disease states on alpha1 -adrenoceptor binding and signal transduction parameters in isolated perfused heart: quantification by pharmacokinetic pharmacodynamic modelling. AB - OBJECTIVES: To employ a pharmacokinetic-pharmacodynamic modelling approach for analysing the effect of experimental endotoxemia and mild hypoxia on alpha1 adrenoceptor (alpha1 AR) binding and signal transduction. METHODS: In Langendorff perfused rat hearts, phenylephrine was continuously infused, and [(3) H]-prazosin was injected as single dose (infused over 1 min). Simultaneous analysis of the time courses of prazosin outflow concentration and inotropic response (left ventricular developed pressure) using an agonist-antagonist interaction model and nonlinear regression allowed to estimate receptor affinity, as well as the parameters of the operational model of agonism. KEY FINDINGS: Both endotoxemia and hypoxia, significantly reduced the maximum response achievable in the system to 67% and 49% of the control group mean, respectively. In addition, endotoxemia decreased the efficiency of stimulus-response coupling and increased the steepness of the stimulus-response curve. In both disease models, no change in receptor affinity and density were found. CONCLUSIONS: The results revealed the causes of reduced alpha1 AR-mediated inotropic responsiveness in endotoxemia and hypoxia. In contrast with traditional dose-response studies, it was possible to quantify separately the underlying changes in alpha1 AR binding and signal transduction. PMID- 24237132 TI - Incorporation of computed tomography and magnetic resonance imaging function into NaYF4:Yb/Tm upconversion nanoparticles for in vivo trimodal bioimaging. AB - Rational design and fabrication of multimodal imaging nanoprobes are of great significance for in vivo imaging. Here we report the fabrication of a multishell structured NaYF4:Yb/Tm@NaLuF4@NaYF4@NaGdF4 nanoprobe via a seed-mediated epitaxial growth strategy for upconversion luminescence (UCL), X-ray computed tomography (CT), and magnetic resonance (MR) trimodal imaging. Hexagonal phase NaYF4:Yb/Tm is used as the core to provide UCL, while the shell of NaLuF4 is epitaxially grown on the core not only to provide an optically inert layer for enhancing the UCL but also to serve as a contrast agent for CT. The outermost NaGdF4 shell is fabricated as a thin layer to give the high longitudinal relaxivity (r1) desired for MR imaging. The transition shell layer of NaYF4 not only provides an interface to facilitate the formation of NaGdF4 shell but also inhibits the energy transfer from inner upconversion activator to surface paramagnetic Gd(3+) ions. The fabricated multishell structured nanoprobe shows intense near-infrared UCL, high r1 value of 3.76 mM(-1) s(-1), and in vitro CT contrast effect. The multishell structured nanoprobe offers great potential for in vivo UCL/CT/MR trimodal imaging. Further covalent bonding of folic acid makes the multishell structured nanoprobe promising for in vivo targeted UCL imaging of tumor-bearing mice. PMID- 24237137 TI - Catalytic direct beta-arylation of simple ketones with aryl iodides. AB - Herein we report a direct beta-arylation of simple ketones with widely available aryl iodides, combining palladium-catalyzed ketone oxidation, aryl-halide activation, and conjugate addition through a single catalytic cycle. Simple cyclic ketones with different ring-sizes, as well as acyclic ketones, can be directly arylated at the beta-position with complete site-selectivity and excellent functional group tolerance. PMID- 24237133 TI - Allotransplantation of kidney from unrelated living donor with loin pain haematuria syndrome. PMID- 24237131 TI - Signaling pathways controlling skeletal muscle mass. AB - The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle. PMID- 24237138 TI - Proteomic analysis of yeast mutant RNA exosome complexes. AB - The yeast exosome is a conserved multiprotein complex essential for RNA processing and degradation. The complex is formed by a nine-subunit core that associates with two hydrolytic 3'-5' exoribonucleases. Although catalytically inert, the assembly of this nine-subunit core seems to be essential for the exosome activity, as mutations in regions that do not directly bind RNA or are not in the active sites of the exonucleases impair the function of the complex. Previously isolated mutations in the exosome core subunit Rrp43p have been shown to negatively affect the function of the complex. With the aim of investigating the effect of these mutations on the complex stability and activity, Rrp43p and its mutant forms were purified by means of the TAP method. Mass spectrometry analyses showed that lower amounts of the exosome subunits are copurified with the mutant Rrp43p proteins. Additionally, by decreasing the stability of the exosome, other nonspecific protein interactions are favored (the data have been deposited to the ProteomeXchange with identifier PXD000580). Exosome copurified with mutant Rrp43p exhibited increased exonuclease activity, suggesting higher dissociation constants for these mutant complexes. Therefore, data reported here indicate that complexes containing a mutant Rrp43p exhibit decreased stability and provide information on additional protein interactions. PMID- 24237139 TI - Caregiver roles in families affected by Huntington's disease: a qualitative interview study. AB - AIM: The objective of this study was to explore family caregivers' experiences with the impact of Huntington's disease (HD) on the family structure and roles in the family. METHODOLOGY: We interviewed 15 family caregivers in families affected by HD, based on a semi-structured interview guide. The participants were recruited through hospital departments and a lay organisation for HD in Norway. Data from the interviews were analysed with systematic text condensation. RESULTS: Huntington's disease could have a substantial impact on the family system, the shape of roles among family members and the hierarchical order between spouses, partners, and parents and children. The relationship between spouses and partners changed during the course of the disease. A reciprocal relationship was difficult to maintain, as the role as carer overshadowed other roles. Children of an affected parent could compensate for impairments by taking on adult responsibilities, and in some families, a child had the role as main caregiver. The increasing need for care could cause conflicts between the role as family member and family caregiver. The burden of care within the family could fragment and isolate the family. CONCLUSIONS: Huntington's disease has a major impact on family systems. Caregiver roles are shaped by impairments in the affected family member and corresponding dynamic adoption and change in roles within the family. Making assessments of the family structure and roles, professionals may understand more about how to care for and support individuals in their role as family members and caregivers in different stages of the disease and family life cycle. PMID- 24237141 TI - Structure and functions of syndecans in vertebrates. AB - Syndecans constitute a family of transmembrane proteoglycans that perform multiple functions during development, damage repair, tumor growth, angiogenesis, and neurogenesis. Through mediating binding of a great number of extracellular ligands to their receptors, these proteoglycans trigger a cascade of reactions regulating, thereby, various processes in a cell: cytoskeleton formation, proliferation, differentiation, adhesion, and migration. In fibroblasts, syndecans are responsible for cell adhesion by modulating functions of integrins through interaction with fibronectin at the external side of a cell and with cytoskeleton and signaling molecules inside the cell. The extracellular domain of syndecans is subjected to periodic shedding from the cell membrane. This process may be stimulated in response to inflammation, tissue damage, and other pathological manifestations. Cleaved domain may act as either competitive inhibitor or activator of signaling cascades. This review summarizes and analyzes the available data regarding structure, main biochemical properties, and functions of syndecans in vertebrates. PMID- 24237142 TI - Molecular mechanisms of apoptosis. structure of cytochrome c-cardiolipin complex. AB - One of the functions of cytochrome c in living cells is the initiation of apoptosis by catalyzing lipid peroxidation in the inner mitochondrial membrane, which involves cytochrome c bound with acidic lipids, especially cardiolipin. In this paper the results of studies of cytochrome c-cardiolipin complex structure carried out by different authors mainly on unilamellar cardiolipin-containing phospholipid liposomes are critically analyzed. The principal conclusion from the published papers is that cytochrome c-cardiolipin complex is formed by attachment of a cytochrome c molecule to the membrane surface via electrostatic interactions and the subsequent penetration of one of the fatty-acid cardiolipin chains into the protein globule, this being associated with hydrophobic interactions that break the >Fe.*.S(Met80) coordinate bond and giving rise to appearance of cytochrome c peroxidase activity. Nevertheless, according to data obtained in our laboratory, cytochrome c and cardiolipin form spherical nanoparticles in which protein is surrounded by a monolayer of cardiolipin molecules. Under the action of cooperative forces, the protein in the globule expands greatly in volume, its conformation is modified, and the protein becomes a peroxidase. In extended membranes, such as giant monolayer liposomes, and very likely in biological membranes, the formation of nanospheres of cytochrome c-cardiolipin complex causes fusion of membrane sections and dramatic chaotization of the whole membrane structure. The subsequent disintegration of the outer mitochondrial membrane is accompanied by cytochrome c release from the mitochondria and triggering of a cascade of programmed cell death reactions. PMID- 24237140 TI - The Pseudomonas syringae effector HopF2 suppresses Arabidopsis immunity by targeting BAK1. AB - Pseudomonas syringae delivers a plethora of effector proteins into host cells to sabotage immune responses and modulate physiology to favor infection. The P. syringae pv. tomato DC3000 effector HopF2 suppresses Arabidopsis innate immunity triggered by multiple microbe-associated molecular patterns (MAMP) at the plasma membrane. We show here that HopF2 possesses distinct mechanisms for suppression of two branches of MAMP-activated MAP kinase (MAPK) cascades. In addition to blocking MKK5 (MAPK kinase 5) activation in the MEKK1 (MAPK kinase kinase 1)/MEKKs-MKK4/5-MPK3/6 cascade, HopF2 targets additional component(s) upstream of MEKK1 in the MEKK1-MKK1/2-MPK4 cascade and the plasma membrane-localized receptor like cytoplasmic kinase BIK1 and its homologs. We further show that HopF2 directly targets BAK1, a plasma membrane-localized receptor-like kinase that is involved in multiple MAMP signaling. The interaction between BAK1 and HopF2 and between two other P. syringae effectors, AvrPto and AvrPtoB, was confirmed in vivo and in vitro. Consistent with BAK1 as a physiological target of AvrPto, AvrPtoB and HopF2, the strong growth defects or lethality associated with ectopic expression of these effectors in wild-type Arabidopsis transgenic plants were largely alleviated in bak1 mutant plants. Thus, our results provide genetic evidence to show that BAK1 is a physiological target of AvrPto, AvrPtoB and HopF2. Identification of BAK1 as an additional target of HopF2 virulence not only explains HopF2 suppression of multiple MAMP signaling at the plasma membrane, but also supports the notion that pathogen virulence effectors act through multiple targets in host cells. PMID- 24237143 TI - Bioinformatics analysis of protein interaction networks: statistics, topologies, and meeting the standards of experimental biologists. AB - In recent years, bioinformatics analyses of protein networks have allowed researchers to obtain exceptional theoretical predictions and subsequent experimental confirmations. The current view is that protein networks are scale free networks and have a topology analogous to that of transport networks, the Internet, and social networks. However, an alternative hypothesis exists in which protein networks and scale-free networks possess significantly different properties. In this work, we show that existing information is insufficient to describe protein networks as scale-free networks. PMID- 24237144 TI - Directed evolution and characterization of atrazine chlorohydrolase variants with enhanced activity. AB - Atrazine chlorohydrolase (AtzA, EC 3.8.1.8) has attracted widespread interests as it catalyzes conversion of toxic atrazine to nontoxic hydroxyatrazine and can be used in the biodegradation of atrazine. To facilitate this application, a Haematococcus pluvialis-based method was applied to screen AtzA variants from a random mutagenesis library. Eight variants with enhanced enzyme activity were obtained. They showed 2.7- to 5.0-fold increase in specific activity compared with the wild type. Sequencing revealed that the two most active variants contained single substitution at Val12 and Leu395, respectively, while several improved variants contained substitutions at the four sites of Met315, His399, Asn429, and Val466 simultaneously, indicating that these residues contribute to the enzyme activity of AtzA. Kinetic analysis showed that five variants decreased the Km value 0.6- to 0.9-fold, whereas all the variants increased the catalytic efficiency (kcat/Km value) 2.5- to 4.1-fold compared to the wild type. The modeled three-dimensional structure showed that AtzA is comprised of a typical (beta/alpha)8 domain of the amidohydrolase superfamily and a dual beta-sheet domain. An iron ion and five ligand-binding residues are located in the beta barrel core of the (beta/alpha)8 domain. Some substituted residues are involved in hydrogen bond formation in the (beta/alpha)8-neighboring beta-sheet. PMID- 24237145 TI - Improvement of the efficiency of transglycosylation catalyzed by alpha galactosidase from Thermotoga maritima by protein engineering. AB - At high concentrations of p-nitrophenyl-alpha-D-galactopyranoside (pNPGal) as a substrate, its hydrolysis catalyzed by alpha-galactosidase from Thermotoga maritima (TmGalA) is accompanied by transglycosylation resulting in production of a mixture of (alpha1,2)-, (alpha1,3)-, and (alpha1,6)-p-nitrophenyl (pNP) digalactosides. Molecular modeling of the reaction stage preceding the formation of the pNP-digalactosides within the active site of the enzyme revealed amino acid residues which modification was expected to increase the efficiency of transglycosylation. Upon the site-directed mutagenesis to the predicted substitutions of the amino acid residues, genes encoding the wild type TmGalA and its mutants were expressed in E. coli, and the corresponding enzymes were isolated and tested for the presence of the transglycosylating activity in synthesis of different pNP-digalactosides. Three mutants, F328A, P402D, and G385L, were shown to markedly increase the total transglycosylation as compared to the wild type enzyme. Moreover, the F328A mutant displayed an ability to produce a regio-isomer with the (alpha1,2)-bond at yield 16-times higher than the wild type TmGalA. PMID- 24237146 TI - Proteasomes in the brain of beta2-microglobulin knockout mice. AB - MHC class I molecules play an important role in synaptic plasticity of the mammalian nervous system. Proteolytic complexes (proteasomes) produce oligopeptides that are presented on cell surfaces in complexes with MHC class I molecules and regulate many cellular processes beside this. The goal of the present work was to study peculiarities in functioning of proteasomes and associated signaling pathways along with evaluation of NeuN and gFAP expression in different sections of the brain in mice with knockout of beta2-microglobulin, a constituent of MHC class I molecules. It was found that the frontal cortex and the brainstem, structures with different ratio of NeuN and gFAP expression, are characterized by opposite changes in the proteasome pool under constant total proteasome levels in B2m-knockout mice in comparison with those in control animals. ChTL-activity as well as expression of LMP7 immune subunit and PA28 regulator of proteasomes was elevated in the cortex of B2m-knockout mice, while these indicators were decreased in the brainstem. The concentrations of the signaling molecules nNOS and HSP70 in B2m-knockout mice were increased in the cortex, while being decreased in the brainstem, and this indicates the possibility of control of expression of the LMP7 subunit and the regulator PA28 by these molecules. Changes in the proteasome pool observed in striatum of B2m knockout mice are similar to those observed in the brainstem. At the same time, the cerebellum is characterized by a specific pattern of proteasome functioning in comparison with that in all other brain structures. In cerebellum the expression of immune subunits LMP7 and LMP2 and the regulator PA28 was increased, while expression of regulator PA700 was decreased. Deficiency of NeuN and gFAP was revealed in most brain compartments of B2m-knockout mice. Thus, increased expression of the above-mentioned immune subunits and the proteasome regulator PA28 in the cortex and cerebellum may compensate disturbances revealed in the brain structures and the absence of MHC class I molecules. Apparently, this promotes production of peptides necessary for cell-to-cell interactions and maintains nervous system plasticity in B2m-knockout mice. PMID- 24237147 TI - 3-O-methoxyimino group inhibits interactions between progestins and blood transcortin. AB - The interactions between E- and Z-isomers of 3-O-methoxyimino-pregn-4-ene-20-one and its 17alpha-hydroxy derivative and transcortin from human blood were investigated. The substitution of the progesterone 3-oxo group for a 3-O methoxyimino group was shown to diminish the affinity of the steroid for transcortin by approximately one order of magnitude irrespective of the substituent's orientation. The data suggests that progesterone derivatives substituted thereby must have higher bioavailability compared to progesterone and must not significantly affect the biodynamics of glucocorticoid in vivo. PMID- 24237148 TI - Inhibition of Mn(2+)-induced error-prone DNA synthesis with Cd(2+) and Zn(2+). AB - Bivalent metal cations are key components in the reaction of DNA synthesis. They are necessary for all DNA polymerases, being involved as cofactors in catalytic mechanisms of nucleotide polymerization. It is also known that in the presence of Mn2+ the accuracy of DNA synthesis is considerably decreased. The findings of this work show that Cd2+ and Zn2+ selectively inhibit the Mn2+-induced error prone DNA polymerase activity in extracts of cells from human and mouse tissues. Moreover, these cations in low concentrations also can efficiently inhibit the activity of homogeneous preparations of DNA polymerase iota (Pol iota), which is mainly responsible for the Mn2+-induced error-prone DNA polymerase activity in cell extracts. Using a primary culture of granular cells from postnatal rat cerebellum, we show that low concentrations of Cd2+ significantly increase cell survival in the presence of toxic Mn2+ doses. Thus, we have shown that in some cases low concentrations of Cd2+ can display a positive influence on cells, whereas it is widely acknowledged that this metal is not a necessary microelement and is toxic for organisms. PMID- 24237149 TI - Disaccharide 1-phosphate polymers of some representatives of the Bacillus subtilis group. AB - Disaccharide 1-phosphate polymers as well as teichoic acids of various structures have been found in the cell walls of the representatives of the Bacillus subtilis group, namely Bacillus subtilis subsp. spizizenii VKM B-720 and VKM B-916, B. subtilis VKM B-517, and Bacillus vallismortis VKM B-2653(T). Disaccharide 1 phosphate polymers are composed of repeating units of the following structure: -P 4)-beta-D-GlcpNAc-(1->6)-alpha-D-Galp-(1-, the N-acetylglucosamine residues are partially acetylated at positions O3 and O6 (VKM B-720 and VKM B-916); -P-4)-beta D-Glcp-(1->6)-alpha-D-GlcpNAc-(1-, the glucopyranose residues are partially acetylated at positions O2 or O3 (VKM B-517); -P-6)-alpha-D-GlcpNH3(+)/alpha-D GlcpNAc-(1->2)-alpha-D-Glcp-(1-, the N-acetylglucosamine residues are partially deacetylated (VKM B-2653(T)). The structures of the two last disaccharide 1 phosphate polymers have not been reported so far for Gram-positive bacteria. The teichoic acids in the studied strains are O-D-alanyl-1,5-poly(ribitol phosphates) substituted with beta-D-glucopyranose (VKM B-517, VKM B-720, VKM B-916) or 2 acetamido-2-deoxy-beta-D-glucopyranose (VKM B-2653(T)). The structures of the phosphate-containing polymers have been studied by chemical methods and by NMR spectroscopy. PMID- 24237150 TI - Mitochondria are targets for the antituberculosis drug rifampicin in cultured epithelial cells. AB - Rifampicin is a widely used drug for antituberculosis therapy. Its target is the bacterial RNA polymerase. After entry into the human or mammalian organism, rifampicin is accumulated in cells of epithelial origin (kidneys, liver, lungs) where it induces apoptosis, necrosis, and fibrosis. The purpose of this study was to determine the intracellular mechanisms leading to rifampicin-induced pathological changes and cell death. We analyzed the survival and state of the chondriome of cultured epithelial cells of the SPEV line under the influence of rifampicin. Our data show that the drug induces pronounced pathological changes in the network and ultrastructure of mitochondria, and their dysfunction results in excessive production of reactive oxygen species and release of cytochrome c. These data suggest the initiation of the mitochondrial pathway of apoptosis. Simultaneously, we observed inhibition of cell proliferation and changes in morphology of the epithelial cells toward fibroblast-like appearance, which could indicate induction of epithelial-mesenchymal transition. Thus, mitochondria are the main potential target for rifampicin in cells of epithelial origin. We suggest that similar mechanisms of pathological changes can be induced in vivo in organs and tissues accumulating rifampicin during chemotherapy of bacterial infectious diseases. PMID- 24237151 TI - Structural characterization of enzymatically synthesized dextran and oligosaccharides from Leuconostoc mesenteroides NRRL B-1426 dextransucrase. AB - Leuconostoc mesenteroides NRRL B-1426 dextransucrase synthesized a high molecular mass dextran (>2 * 10(6) Da) with ~85.5% alpha-(1->6) linear and ~14.5% alpha-(1 >3) branched linkages. This high molecular mass dextran containing branched alpha (1->3) linkages can be readily hydrolyzed for the production of enzyme-resistant isomalto-oligosaccharides. The acceptor specificity of dextransucrase for the transglycosylation reaction was studied using sixteen different acceptors. Among the sixteen acceptors used, isomaltose was found to be the best, having 89% efficiency followed by gentiobiose (64%), glucose (30%), cellobiose (25%), lactose (22.5%), melibiose (17%), and trehalose (2.3%) with reference to maltose, a known best acceptor. The beta-linked disaccharide, gentiobiose, showed significant efficiency for oligosaccharide production that can be used as a potential prebiotic. PMID- 24237152 TI - Ozone-induced oxidative modification of fibrinogen molecules. AB - Ozone-induced oxidation of fibrinogen has been investigated. The conversion of oxidized fibrinogen to fibrin catalyzed either by thrombin or by a reptilase-like enzyme, ancistron, in both cases is accompanied by production of gels characterized by a higher weight/length ratio of fibrils in comparison with the native fibrin gels. IR spectra of the D and E fragments isolated from unoxidized and oxidized fibrinogen suggest a noticeable transformation of functional groups by oxidation. A decrease in content of N-H groups in the peptide backbone and in the number of C-H bonds in aromatic structures, as well as a decrease in the intensity of the C-H valence vibrations in aliphatic fragments CH2 and CH3 were found. The appearance in the differential spectra of the D fragments of rather intense peaks in the interval of 1200-800 cm(-1) clearly indicates the interaction of ozone with amino acid residues of methionine, tryptophan, histidine, and phenylalanine. Comparison of the differential spectra for the D and E fragments suggests that fibrinogen fragment D is more sensitive to the oxidant action than fragment E. Using EPR spectroscopy, differences are found in the spectra of spin labels bound with degradation products of oxidized and unoxidized fibrinogen, the D and E fragments, caused by structural and dynamical modifications of the protein molecules in the areas of localization of the spin labels. The relationship between the molecular mechanism of oxidation of fibrinogen and its three-dimensional structure is discussed. PMID- 24237153 TI - Comparative study of biochemical properties of glucoamylases from the filamentous fungi Penicillium and Aspergillus. AB - Here we report the first isolation to homogeneous forms of two glucoamylases from the fungus Penicillium verruculosum and their study in comparison with known glucoamylases from Aspergillus awamori and Aspergillus niger. Genes that encode glucoamylases from P. verruculosum were cloned and expressed in the fungus Penicillium canescens, and the recombinant glucoamylases were obtained with subsequent study of their molecular weights, isoelectric points, optimal temperature and pH values, and stability. The catalytic activities of the recombinant glucoamylases were determined in relation to soluble potato starch. Changes in molecular mass distribution and content of low molecular weight products during starch hydrolysis by glucoamylases from P. verruculosum, A. awamori, and A. niger were studied. An exo-depolymerization mechanism was established to be the pathway for destruction of starch by the glucoamylases. PMID- 24237154 TI - Why do primordial germ cells migrate through an embryo and what does it mean for biological evolution? AB - An explanation of the role of primordial germ cell (PGC) migration during embryogenesis is proposed. According to the hypothesis, various PGCs during their migrations through an early embryo are contacting with anlagen of organs and acquiring nonidentical organ specificities. An individual PGC gets such an organ specificity, which corresponds to specificity of the first anlage with which this PGC has the first contact. As a result, the cellular descendants of PGCs (oocytes or spermatocytes) will express nonidentical organ-specific receptors, hence becoming functionally heterogeneous. Therefore, each clone of germ cells becomes capable of recognizing specifically the molecular signals that correspond only to "its" organ of the body. Such signals are produced by the body's organ when it functions in an extreme mode. Signals from the "exercising" organ of the body are delivered to the gonad only via the brain retransmitter, which is composed of neurons grouped as virtual organs of a homunculus. Homunculi are so-called somatotopic maps of the skeletomotor and other parts of the body represented in the brain. Signals, as complexes of regulatory RNAs and proteins, are transported from the "exercising" organ of the body to the corresponding virtual organ of the homunculus where they are processed and then forwarded to the gonad. The organ specific signal will be selectively recognized by certain gametocytes according to their organ specificity, and then it will initiate the directed epimutation in the gametocyte genome. The nonrandomness of the gene order in chromosomes, that is the synteny and genetic map, is controlled by the so-called creatron that consolidates the soma and germline into a united system, providing the possibility of evolutionary responses of an organism to environmental influences. PMID- 24237156 TI - Systematic review of the psychometric properties and theoretical grounding of instruments evaluating self-care in people with type 2 diabetes mellitus. AB - AIM: To determine the psychometric properties and theoretical grounding of instruments that evaluate self-care behaviour or barriers in people with type 2 diabetes. BACKGROUND: There are many instruments designed to evaluate self-care behaviour or barriers in this population, but knowledge about their psychometric validation processes is lacking. DESIGN: Systematic review. DATA SOURCES: We conducted a search for psychometric or validation studies published between January 1990-December 2012. We carried out searches in Pubmed, CINAHL, PsycINFO, ProQuolid, BibliPRO and Google SCHOLAR to identify instruments that evaluated self-care behaviours or barriers to diabetes self-care. REVIEW METHODS: We conducted a systematic review with the following inclusion criteria: Psychometric or clinimetric validation studies that included patients with type 2 diabetes (exclusively or partially) and which analysed self-care behaviour or barriers to self-care and proxies like self-efficacy or empowerment, from a multidimensional approach. Language: Spanish or English. Two authors independently assessed the quality of the studies and extracted data using Terwee's proposed criteria: psychometrics properties, dimensionality, theoretical ground and population used for validation through each included instrument. RESULTS: Sixteen instruments achieved the inclusion criteria for the review. We detected important methodological flaws in many of the selected instruments. Only the Self management Profile for Type 2 Diabetes and Problem Areas in Diabetes Scale met half of Terwee's quality criteria. CONCLUSION: There are no instruments for identifying self-care behaviours or barriers elaborated with a strong validation process. Further research should be carried out to provide patients, clinicians and researchers with valid and reliable instruments that are methodologically solid and theoretically grounded. PMID- 24237157 TI - In vitro evaluation of a novel autologous aortic valve (biovalve) with a pulsatile circulation circuit. AB - We have used in-body tissue architecture technology to develop an autologous valved conduit with intact sinuses of Valsalva (biovalve). In this study, we fabricated three different forms of biovalves and evaluated their function in vitro using a mock circulation model to determine the optimal biovalve form for aortic valve replacement. A cylindrical mold for biovalve organization was placed in a dorsal subcutaneous pouch of a goat, and the implant that was encapsulated with connective tissue was extracted 2 months later. The cylindrical mold was removed to obtain the biovalve (16 mm inside diameter) that consisted of pure connective tissue. The biovalve was connected to a pulsatile mock circulation system in the aortic valve position. The function of the three biovalves (biovalve A: normal leaflets with the sinuses of Valsalva; biovalve B: extended leaflets with the sinuses of Valsalva; biovalve C: extended leaflets without the sinuses of Valsalva) was examined under pulsatile flow conditions using saline. In addition, the mock circuit was operated continuously for 40 days to evaluate the durability of biovalve C. The regurgitation rate (expressed as a percent of the mean aortic flow rate during diastole) was 46% for biovalve A but only 3% for biovalves B and C. The durability test demonstrated that even after biovalve C pulsated more than four million times (heart rate, 70 bpm; mean flow rate, 5.0 L/min; mean aortic pressure, 92 mm Hg), stable continuous operation was possible without excessive reduction of the flow rate or bursting. The developed biovalve demonstrated good function and durability in this initial in vitro study. PMID- 24237155 TI - Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus. AB - The type 1 diabetes-associated 16p13 locus contains the CLEC16A gene. Its preferential immune cell expression suggests involvement in autoimmunity. Given its elevated expression in dendritic and B cells - known professional antigen presenting cells (APCs) - we hypothesize that C-type lectin domain family 16 member A (CLEC16A) may be involved in T cell co-stimulation and consequent activation and proliferation. We also sought to identify CLEC16A's subcellular localization. The effect of the CLEC16A knock-down (KD) on B cell co-stimulation and activation of T cells was tested in human lymphoblastoid cell lines (LCLs) by co-culture with CD4(+) T cells. T cell activation and proliferation were determined by flow-cytometric analysis of CD69 and CD25 expression and carboxyfluorescein succinimidyl ester (CFSE) dilution, respectively. CLEC16A subcellular localization in K562 cells was examined by immunofluorescence. We show that the CLEC16A KD did not affect the tested indices of lymphoblastoid cell line (LCL) APC capacity. Additionally, the percentage of activated T cells following LCL co-culture was not affected significantly by the CLEC16A KD. T cells co-cultured with KD or control LCLs also exhibited similar cell division profiles. CLEC16A co-localized with an endoplasmic reticulum (ER) marker, suggesting that it may be an ER protein. In conclusion, CLEC16A may not be involved in T cell co-stimulation. Additional studies on CLEC16A, accounting for its ER localization, are needed to uncover its biological role. PMID- 24237158 TI - Rhamnolipid biosurfactant and soy protein act as effective stabilizers in the aggregation and transport of palladium-doped zerovalent iron nanoparticles in saturated porous media. AB - Palladium-doped nanosized zerovalent iron (Pd-NZVI) particles can contribute to the transformation of chlorinated solvents and various other contaminants into innocuous products. To make Pd-NZVI an effective in situ subsurface remediation agent, these particles need to migrate through a targeted contaminated area. However, previous studies have reported very limited mobility of these particles in the groundwater environment and attributed it to rapid aggregation and subsequent pore plugging. In this study, we systematically investigated the influence of selected natural and nontoxic organic macromolecules (carboxymethyl cellulose, rhamnolipid biosurfactants, and soy protein) on the aggregation and transport behavior of bare and coated Pd-NZVI. Aggregation behavior was investigated using dynamic light scattering by monitoring the evolution of hydrodynamic diameter as a function of time, whereas transport behavior was investigated by conducting water-saturated sand-packed column experiments. While bare Pd-NZVI is prone to rapid aggregation, we observed good colloidal stability and concurrent enhanced transport of Pd-NZVI coated with carboxymethyl cellulose, rhamnolipid biosurfactants, and soy protein. Each surface modifier performed well at lower ionic strength (IS) (10 mM NaHCO3), and one of the rhamnolipid surface modifiers (JBR215) significantly enhanced transport of 150 mg/L Pd-NZVI at concentrations as low as 10 mg/L total organic carbon. However, an increase in the solution IS induced significant Pd-NZVI aggregation with a simultaneous decrease in the transport potential in accordance with the DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory of colloidal stability. Nonetheless, at the highest IS (300 mM NaHCO3) investigated, the mobility of rhamnolipid-coated Pd NZVI is significantly higher than that of Pd-NZVI coated with the other surface modifiers, suggesting that biosurfactants may be the most suitable surface modifiers in field application. Overall, this study emphasizes how stabilization of Pd-NZVI with natural macromolecules such as rhamnolipids can improve the transport potential of these reactive nanoparticles in subsurface remediation applications at concentrations significantly lower than those of other commonly used polymers. PMID- 24237159 TI - Overexpression of stress-inducible OsBURP16, the beta subunit of polygalacturonase 1, decreases pectin content and cell adhesion and increases abiotic stress sensitivity in rice. AB - Polygalacturonase (PG), one of the hydrolases responsible for cell wall pectin degradation, is involved in organ consenescence and biotic stress in plants. PG1 is composed of a catalytic subunit, PG2, and a non-catalytic PG1beta subunit. OsBURP16 belongs to the PG1beta-like subfamily of BURP-family genes and encodes one putative PG1beta subunit precursor in rice (Oryza sativa L.). Transcription of OsBURP16 is induced by cold, salinity and drought stresses, as well as by abscisic acid (ABA) treatment. Analysis of plant survival rates, relative ion leakage rates, accumulation levels of H2 O2 and water loss rates of leaves showed that overexpression of OsBURP16 enhanced sensitivity to cold, salinity and drought stresses compared with controls. Young leaves of Ubi::OsBURP16 transgenic plants showed reduced cell adhesion and increased cuticular transpiration rate. Mechanical strength measurement of Ubi::OsBURP16 plants showed that reduced force was required to break leaves as compared with wild type. Transgenic rice showed enhanced PG activity and reduced pectin content. All these results suggested that overexpression of OsBURP16 caused pectin degradation and affected cell wall integrity as well as transpiration rate, which decreased tolerance to abiotic stresses. PMID- 24237161 TI - High-throughput extraction of beta-carotene from Blakeslea trispora based on a newly developed setup. AB - Rapid and efficient extraction of bioactive compounds from biomass for sample analysis presents one of the major challenges in high-productive strain screening and bioprocess development. In this work, a high-throughput method based on a new setup was developed for the extraction of beta-carotene from Blakeslea trispora. After the cell was completely disrupted by high-throughput machinery grinding, beta-carotene was completely extracted by chloroform and dimethylsulfoxide (1:1, v/v). According to the experimental results, the newly developed high-throughput extraction (HTPE) method could simultaneously process 96 samples within 30 Min, and only 5-mL solvent was used for each sample. The sufficient extraction of beta carotene by the HTPE method, which was confirmed by the conventional reference extraction method, further demonstrated that the newly developed HTPE method was more efficient and economical than the methods developed previously for the extraction of beta-carotene. PMID- 24237162 TI - Proposals to broaden the UK bolar defence. PMID- 24237160 TI - Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3 dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites. AB - The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [(3)H]S-1 via S2. PMID- 24237163 TI - Parallel imports in the enlarged EU: the specific mechanism. PMID- 24237164 TI - US Supreme Court rules on landmark gene patent case. PMID- 24237165 TI - Practical implications of the unitary patent system in Europe. PMID- 24237166 TI - WIPO Re:Search: a consortium catalyzing research and product development for neglected tropical diseases. PMID- 24237169 TI - A new patent-based approach for technology mapping in the pharmaceutical domain. AB - The key factor in decision-making is the quality of information collected and processed in the problem analysis. In most cases, patents represent a very important source of information. The main problem is how to extract such information from the huge corpus of documents with a high recall and precision, and in a short time. This article demonstrates a patent search and classification method, called Knowledge Organizing Module, which consists of creating, almost automatically, a pool of patents based on polysemy expansion and homonymy disambiguation. Since the pool is done, an automatic patent technology landscaping is provided for fixing the state of the art of our product, and exploring competing alternative treatments and/or possible technological opportunities. An exemplary case study is provided, it deals with a patent analysis in the field of verruca treatments. PMID- 24237170 TI - Modulating Ca2+ release by the IP3R/Ca2+ channel as a potential therapeutic treatment for neurological diseases. AB - Recent research into neurodegenerative disorders found that their pathogeneses have a link to the inositol 1,4,5-trisphosphate receptors (IP3R). This is encouraging, because despite extensive efforts, researchers have not fully understood the pathophysiologies of those disorders, and have yet to find the cure. The IP3R provides a possible point of convergence that new therapeutic drugs can target. This review highlights patents that manipulate activities of the IP3R. They generally involve the use of peptides designed from the amino acid sequences of IP3R-binding proteins, and of buffers that limit the availability of its ligand, IP3. Additionally, one of them details the use of a chromophore conjugated small synthetic molecule to directly inhibit the IP3R in a highly spatiotemporally specific manner. Although many of them have only been tested in vitro or are in the early stages of in vivo application, more research-effective therapies for neurodegenerative diseases can hopefully be developed. PMID- 24237171 TI - Engineered antibody variable and constant domains as therapeutic candidates. AB - Monoclonal antibodies have been successfully used for the therapy of various diseases. However, because of their large size (~150 kD), many limitations have also been found during their development and manufacture. The use of antibody fragments with smaller sizes is one of the strategies to overcome these limitations. Antibody heavy chain variable domains (12~15 kD) have already been widely used for the development of variable domain-based engineered antibody domains (termed V-based eAds) targeting different antigens. Recently, antibody second heavy chain constant domains (~12 kD) were proposed as novel scaffolds for library construction and selection of specific binders termed constant domain based eAds (C-based eAds) as novel candidate therapeutics, which might also confer additional crystallizable fragment functions. Both V- and C-based eAds are promising therapeutic candidates. This review summarizes progress in the development of eAds, and discusses the related patents and their potential applications. PMID- 24237172 TI - Inhaled antibiotics to treat lung infection. AB - The development of inhaled antibiotics to treat lung infection is an active field, with four approved products in the USA and more in the late stages of clinical development. The efficacies of TOBI(r) tobramycin (Novartis) and Cayston(r) aztreonam lysate (Gilead), the approved inhaled antibiotics for cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa, have been well documented. Recent approvals for a second-generation tobramycin solution, Bethkis(r), and a tobramycin powder formulation in a dry-powder inhaler (DPI), TOBI Podhaler(r), indicate that the inhaled antibiotic marketplace in CF is becoming very competitive. Other indications are also receiving interest. While there have been a number of recent reviews from a clinical, technical or regulatory perspective in the field of inhaled antibiotics, as well as others focused on a specific product or data from a recent clinical trial, there have not been any that describe the patent coverage of these products. This review addresses that missing piece. PMID- 24237173 TI - Lipid-based nanocarriers for drug delivery and targeting: a patent survey of methods of production and characterization. AB - Among the colloidal vectors proposed for the controlled delivery and targeting of drugs and other biologically active compounds, lipid-based nanocarriers are acquiring an increasing role due to a number of peculiar technological and physical features. Solid lipid nanoparticles, lipid nanocapsules, nanostructured lipid carriers, and drug-lipid conjugates are all examples of how it can be possible to combine the properties of the more acknowledged liposomal systems, such as biocompatibility and biodegradability, with the stability and compositional flexibility, distinctive of polymeric nanosystems. This article introduces recent patents, filed in years 2007-2013, that deal with novel or amended methods of production of the various types of lipid-based nanocarriers. Although a significant gap still remains between basic research and patenting activity in this field, many of the proposed methods can attain an industrial value. Furthermore, the critical analysis of these patents further supports the position that a general revision of patenting systems at an international level would be necessary for nanosized pharmaceutical systems. PMID- 24237175 TI - Acquisition and diversification of tendrilled leaves in Bignonieae (Bignoniaceae) involved changes in expression patterns of SHOOTMERISTEMLESS (STM), LEAFY/FLORICAULA (LFY/FLO), and PHANTASTICA (PHAN). AB - Leaves have undergone structural modifications over evolutionary time, and presently exist in many forms. For instance, in Fabaceae and Bignoniaceae, leaf parts can be modified into tendrils. Currently, no data are available on genic control of tendrilled leaf development outside Fabaceae. Here, we conducted a detailed study of three representatives of Bignonieae: Amphilophium buccinatorium, Dolichandra unguis-cati, and Bignonia callistegioides, bearing multifid, trifid, and simple-tendrilled leaves, respectively. We investigated the structure of their petioles, petiolules, leaflets, and tendrils through histological analyses. Additionally, the expression of SHOOTMERISTEMLESS (STM), PHANTASTICA (PHAN), and LEAFY/FLORICAULA (LFY/FLO) during leaf development was analyzed by in situ hybridizations. Tendrils share some anatomical similarities with leaflets, but not with other leaf parts. Transcripts of both STM and LFY/FLO were detected in leaf primordia, associated with regions from which leaflets and tendril branches originate. PHAN expression was found to be polarized in branched tendrils, but not in simple tendrils. In Bignonieae, tendrils are modified leaflets that, as a result of premature completion of development, become bladeless organs. Bignonieae leaves develop differently from those of peas, as both LFY/FLO and STM are expressed in developing leaves of Bignonieae. Moreover, PHAN is probably involved in tendril diversification in Bignonieae, as it has distinct expression patterns in different leaf types. PMID- 24237176 TI - Attitudes towards female genital mutilation: an integrative review. AB - BACKGROUND: Immigration and globalization processes have contributed to the international dissemination of practices such as female genital mutilation. Between 100 and 400 million girls and women have been genitally mutilated, and every year 3 million girls are at risk of being subjected to female genital mutilation. OBJECTIVES: The objective of this study was to describe the attitudes towards the practice of female genital mutilation in relation to different health systems and the factors that favour its discontinuation. METHODS: An integrative review was performed of publications from the period 2006 to 2013 included in the MedLine, PubMed, LILACS, SciELO, CINAHL and CUIDEN databases. RESULTS: We selected 16 studies focusing on diverse contexts that assessed the attitudes of both men and women regarding the perpetuation of this practice. Ten corresponded to studies conducted in countries of residence. Several areas of investigation were explored (factors contributing to the continuation of female genital mutilation, factors contributing to its discontinuation, feelings about the health system). LIMITATIONS: It is possible that the relevant studies may not have been included given the limitations of the literature review and the invisibility of the phenomenon studied. CONCLUSIONS: This review demonstrates the strong social pressure to which women are subjected as regards the practice of female genital mutilation. However, many other factors can contribute to eroding beliefs and arguments in favour of this practice, such as the globalization, culture and social environment of countries in the West. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses occupy an essential position in detecting and combating these practices. PMID- 24237177 TI - Comparison of primary vaccination regimes for equine influenza: working towards an evidence-based regime. AB - REASONS FOR PERFORMING STUDY: Vaccination is crucial to the control of equine influenza (EI). The study was conducted in an effort to lay the groundwork for achieving international harmonisation of regulatory requirements based on scientific evidence of performance of different vaccination regimes. OBJECTIVES: To evaluate the effectiveness of 3 different primary vaccination regimes: vaccination with the minimal intervals permitted by the racing authorities; vaccination in accordance with the manufacturer's instructions and vaccination with the longest intervals permitted by the racing authorities. STUDY DESIGN: Randomised, prospective clinical trial. METHODS: The 55 seronegative unvaccinated horses in this study were subdivided by age and randomly allocated one of the 3 vaccination regimes. All groups were sampled each time a group was vaccinated and 3-5 weeks post vaccination. Horses were vaccinated with a subunit immune stimulating complex-based vaccine (Equip FT). Antibodies against EI were measured by single radial haemolysis. RESULTS: Lengthening the vaccination intervals increased the immunity gaps between first (V1) and second (V2) doses, and V2 and third dose (V3) but did not inhibit the response to V2 and V3. The response to V2 and V3 was similar irrespective of the regime. Poor responders to V1 were identified in all age groups included in this study but the greatest number of poor responders was among the yearlings. The 2- and 3-year-old horses responded better to vaccination than the weanlings or yearlings. CONCLUSIONS: Longer vaccination intervals permitted by racing authorities increase the periods of susceptibility to EI but they may facilitate strategic vaccination prior to times of increased risk of exposure to virus. The study provides the type of evidence based data necessary to commence meaningful discussion of international harmonisation of EI vaccination requirements. PMID- 24237179 TI - Digestive vacuole membrane in Plasmodium falciparum-infected erythrocytes: relevance to templated nucleation of hemozoin. AB - Crystallization of the malaria pigment hemozoin sequesters the toxic heme byproduct of hemoglobin digestion in Plasmodium -infected red blood cells (RBCs). Recently, we applied electron and X-ray imaging and diffraction methods to elucidate this process. We observed crystals oriented with their {100} faces at the inner membrane surface of the digestive vacuole (DV) of Plasmodium falciparum in parasitized RBCs. Modeling of the soft X-ray tomographic (SXT) images of a trophozoite-stage parasite indicated a 4-16 nm DV membrane thickness, suggesting a possible role for lipid multilayers. Here, we reanalyzed the trophozoite SXT images quantitatively via X-ray absorption to map the DV membrane thickness. Making use of the chemical structure and crystal density of the lipid, we found, predominantly, a bilayer 4.2 nm thick, and the remainder was interpreted as patches ~8 nm thick. Image analysis of electron micrographs also yielded a 4-5 nm DV membrane thickness. The DV lipid membrane is thus mainly a bilayer, so induced hemozoin nucleation occurs primarily via the inner of the membrane's two leaflets. We argue that such a leaflet embodying mono- and di-acyl lipids with appropriate OH or NH bearing head groups may catalyse hemozoin nucleation by stereochemical and lattice match to the {100} crystal face, involving a two dimensional nucleation aggregate of ~100 molecules. PMID- 24237178 TI - Use of contrast-enhanced ultrasonography in chronic pathologic canine testes. AB - Contrast-enhanced ultrasound with sulphur hexafluoride microbubbles was performed in seven healthy dogs without a history of reproductive pathology and with histologically confirmed normal testes and in 42 dogs with chronic scrotal anomalies. All dogs underwent orchiectomy and histological examination. Enhancement patterns and perfusion parameters (peak intensity and regional blood flow) of testes of healthy dogs and testes with chronic lesions were compared. Fourteen non-pathologic and 60 pathologic testes were considered. Forty testes were neoplastic (24 interstitial cell tumours, 9 seminomas, 7 Sertoli cell tumours), 20 were non-neoplastic (16 testicular degenerations, 2 chronic orchitis, 1 testicular atrophy, 1 interstitial cell hyperplasia). In healthy dogs, the contrast medium flow had a rapid homogeneous wash-in and wash-out, with a short peak phase. With contrast ultrasound, testes that were inhomogeneous with a hyperenhancing pattern were associated with neoplasia (sensitivity: 87.5%, specificity: 100%). Lesions with persistent inner vessels and a hypo-to-isoechoic background were significantly associated with seminomas (sensitivity: 77.8%, specificity: 100%). Testes with non-neoplastic lesions were characterized by a scant/moderate homogeneous enhancement. Perfusion parameters were higher in neoplastic lesions. Contrast ultrasound was a feasible diagnostic tool in the assessment of testicular lesions, with hyperenhancement being an important feature in the diagnosis of malignancy. PMID- 24237180 TI - Enabling forbidden processes: quantum and solvation enhancement of nitrate anion UV absorption. AB - We present simulated electronic absorption spectra of isolated and solvated nitrate anion in the UV region, focusing primarily on the absorption into the first absorption band around 300 nm. This weak absorption band in this spectral region is responsible for the generation of NOx in the polar areas or OH(*) radicals in the hydrosphere. The 300 nm absorption band is symmetrically strongly forbidden and coupling of at least two vibrational modes is needed to allow the transition in the isolated nitrate anion. Further symmetry breaking is provided by solvation. In this study we model the absorption spectra of nitrate-water clusters using the combined reflection principle path integral molecular dynamics (RP-PIMD) method. Condensed phase UV spectra are modeled within a cluster continuum model. The calculated spectra are compared with experimental bulk phase measurements and reasonable agreement is found. We also provide a benchmarking of the DFT functionals to be used for a description of the electronically excited states of solvated nitrate anion. PMID- 24237181 TI - Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age. AB - BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross sectional study on 56 AGA-born girls with PA (6.9 +/- 0.6 years) and 33 BMI matched prepubertal AGA-born peers (7.1 +/- 1.0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0.01) and UL standard deviation score (SDS) (P = 0.02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0.05). MOV and MOV SDS correlated with ISIcomp (r = -0.683, P < 0.001; r = -0.760, P < 0.001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0.05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0.731, beta = -4.784, P = 0.001). CONCLUSIONS: Appropriate for gestational age born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS. PMID- 24237182 TI - Characterization of vascular disruption and blood-spinal cord barrier permeability following traumatic spinal cord injury. AB - Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. Spectrophotometry of EB tissue showed maximal BSCB disruption at 24 h postinjury, with significant disruption observed until 5 days postinjury (p<0.01). FITC-LEA-identified functional vasculature was dramatically reduced by 24 h. Similarly, RECA-1 immunohistochemistry showed a significant decrease in the number of vessels at 24 h postinjury, compared to uninjured animals (p<0.01), with slight increases in endogenous revascularization by 10 days postinjury. White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI. PMID- 24237183 TI - In vitro performance analysis of a novel pulsatile diagonal pump in a simulated pediatric mechanical circulatory support system. AB - The objective of this study was to evaluate the pump performance of the third generation Medos diagonal pump, the Deltastream DP3, on hemodynamic profile and pulsatility in a simulated pediatric mechanical circulatory support (MCS) system. The experimental circuit consisted of a Medos Deltastream DP3 pump head and console (MEDOS Medizintechnik AG, Stolberg, Germany), a 14-Fr Terumo TenderFlow Pediatric arterial cannula and a 20-Fr Terumo TenderFlow Pediatric venous return cannula (Terumo Corporation, Tokyo, Japan), and 3 ft of tubing with an internal diameter of in. for both arterial and venous lines. Trials were conducted at flow rates ranging from 250 mL/min to 1000 mL/min (250-mL/min increments) and rotational speeds ranging from 1000 to 4000 rpm (1000-rpm increments) using human blood (hematocrit 40%). The postcannula pressure was maintained at 60 mm Hg by a Hoffman clamp. Real-time pressure and flow data were recorded using a Labview based acquisition system. The pump provided adequate nonpulsatile and pulsatile flow, created more hemodynamic energy under pulsatile mode, and generated higher positive and negative pressures when the inlet and outlet of the pump head, respectively, were clamped. After the conversion from nonpulsatile to pulsatile mode, the flow rates and the rotational speeds increased. In conclusion, the novel Medos Deltastream DP3 diagonal pump is able to supply the required flow rate for pediatric MCS, generate adequate quality of pulsatility, and provide surplus hemodynamic energy output in a simulated pediatric MCS system. PMID- 24237184 TI - TGF-alpha gene variations and increased susceptibility of gastric cancer in an Eastern Chinese Han population. AB - Transforming growth factor-alpha (TGF-alpha) correlates with deep invasion, advanced stage and poor prognosis in gastric cancer. Genetic variants in the 3' untranslated region (UTR) of TGF-alpha gene may influence the stability and post transcriptional regulation of mRNA and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped five polymorphisms in 3'UTR (rs3771527, rs503314, rs473698, rs3732253 and rs538118) and one in 3' near region (rs11466306) of the TGF-alpha gene by polymerase chain reaction-ligation detection reaction methods (PCR-LDR). We found that GA/AA genotype of rs11466306 in the 3' near gene could increase the risk of overall gastric cancer (adjusted OR = 1.499, 95%CI: 1.101-2.041), compared to the wild homozygous GG genotype. Meanwhile, the risk effect was more obvious in the intestinal gastric cancer and gastric noncardia cancer (adjusted OR = 1.682, 95%CI: 1.188-2.380; adjusted OR = 1.495, 95%CI: 1.072-2.086, respectively), but not for the diffuse type and gastric cardia cancer (p > 0.05). CT/TT genotype for rs3732253 in the 3' UTR was associated with increased risk of intestinal gastric cancer (adjusted OR = 1.464, 95%CI: 1.036-2.069), compared to their wild homozygous genotypes. These findings indicate that potentially functional TGF-alpha gene variant may contribute to the risk of intestinal gastric cancer and/or gastric noncardia cancer and could be used as molecular markers for detecting intestinal gastric cancer and/or gastric noncardia cancer in Chinese Han population. PMID- 24237185 TI - A new technique for subtotal (cranial wedge) ostectomy in the treatment of impinging/overriding spinous processes: description of technique and outcome of 25 cases. AB - REASONS FOR PERFORMING STUDY: Surgical management for overriding spinous processes of the thoracolumbar vertebrae (SPs) is often favoured when conservative therapies have failed, pathology is severe, or in competition horses constrained by drug withdrawal periods. OBJECTIVES: To evaluate whether subtotal (cranial wedge) ostectomy represents an effective treatment for overriding SPs, with short surgery time and low complication rates, maintains the contour of the spine and produces a functionally and cosmetically better outcome than previously reported surgical techniques for management of overriding/impinging SPs. STUDY DESIGN: Retrospective study. METHODS: A new technique is described and records were retrieved for 25 cases that had undergone the procedure at Newmarket Equine Hospital between 2009 and 2011. Case records were evaluated for anamnesis, clinical findings and details of surgical and post operative management. Outcome of surgery was assessed by telephone questionnaire with owners, relating to both functional and cosmetic results. RESULTS: Of cases treated using the described technique, 78.9% had resolution of clinical signs and returned to full work and a further 18.2% were improved. Outcome was unrelated to number of SPs resected or mean radiographic grade of impingement. Cosmetic outcome was described as excellent in 81.8% and good in the remainder. Surgery time ranged from 20 to 70 (median 30) min and there were no intra- or post operative complications. CONCLUSIONS: In contrast to previously described amputation techniques, subtotal (cranial wedge) ostectomy removes only impinging portions of SPs. General anaesthesia and lateral recumbency facilitate access and enable a short surgery time. The procedure maintains the contour of the back and has fewer complications, but produces functional outcomes similar to more invasive procedures. PMID- 24237186 TI - Whole-body vibration training increases physical fitness measures without alteration of inflammatory markers in older adults. AB - This study investigated in older adults whether whole-body vibration (WBV) training results in significant increases of physical fitness measures without alterations in markers of inflammation. Sixteen volunteers completed a WBV programme 3 d.wk(-1) during 9 weeks. The programme consisted of lower and upper body unloaded static and dynamic exercises. Training improved significantly several tests which evaluate physical fitness, such as 30-s chair stand, arm curl or chair sit and reach test. There was a significant increase in maximal voluntary isometric contraction (MVIC) between pre- and post-training conditions. Muscle power values, reached at 20, 40 and 60% MVIC, were also significantly greater after training. However, mRNA or protein levels for C-reactive protein, interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and interleukin-10 did not significantly differ from basal values. Our data confirm the usefulness of WBV training for counteracting the loss of muscle strength associated with sarcopenia in older adults and show that WBV training could be a safe training method which induces no inflammatory effects. PMID- 24237187 TI - Oxidative stress reduced by a green tea concentrate and Capsicum combination: synergistic effects. AB - Reactive oxygen species that are produced by aerobic metabolism and signaling cascades have the potential to play important roles in maintaining homeostatic redox and cell proliferation. When the balance between the production and elimination of reactive oxygen species is perturbed toward production, the result is oxidative stress. High levels of oxidative stress are a general characteristic of cancer. The altered redox state within a tumor microenvironment confers a growth advantage through increased proliferation rates, evasion of apoptosis, and increased resistance to therapeutic compounds. We have tested a synergistic combination of green tea-Camellia sinensis-concentrate and powdered Capsicum powder (TeaFenseTM/Capsol-TTM) as a dietary supplement to reduce oxidative stress as an approach to elimination of malignant cells. Here, we demonstrate that the green tea-powdered Capsicum mixture effectively reduces levels of oxidative stress in both cancer (HeLa) and noncancer (MCF-10A) cells as determined from measurements of levels of the oxidative stress indicator Nrf-2 by western blot analysis. Nrf-2 is a transcription factor that controls an antioxidant response element. Increased expression of Nrf-2 is linked to high levels of oxidative stress and vice versa. Based on levels of Nrf-2, the mixture of green tea concentrate plus powdered Capsicum reduced oxidative stress by more than 50% compared with 15% by the green tea concentrate alone. PMID- 24237188 TI - Purified dry extract of Paullinia cupana (guarana) (PC-18) for chemotherapy related fatigue in patients with solid tumors: an early discontinuation study. AB - PURPOSE: Paullinia cupana (guarana) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. METHODS: We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory (BFI) questionnaire scores after 1 week of systemic chemotherapy. PC-18 was administered at 37.5 mg by mouth two times per day (PO bid), starting after 1 week of chemotherapy, for 3 weeks (induction phase). Patients who had an improvement in or stabilization of their BFI scores were randomized to receive either PC-18 at the same dose or placebo for the following 3 weeks (maintenance phase). RESULTS: After PC-18 treatment, the BFI fatigue scores improved or stabilized in 36 out of the 40 patients (mean BFI score difference = 2.503; 95% confidence interval: 1.716-3.375, p = .0002). Three weeks after randomization (16 patients on PC-18 and 17 on placebo), we observed no significant differences in the BFI, Functional Assessment of Chronic Illness Therapy, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores between patients randomized to PC-18 versus placebo. CONCLUSIONS: We conclude that the PC-18 extract may be effective for the treatment of CRF in patients with a variety of solid tumors. A conditioning effect, which was observed in patients who had a beneficial effect of PC-18 on CRF, may explain the better than expected fatigue scores of the placebo-treated patients. PMID- 24237189 TI - Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats. AB - Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz) induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5 mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug. PMID- 24237190 TI - Chromium supplementation for menstrual cycle-related mood symptoms. AB - BACKGROUND: Premenstrual dysphoric disorder (PMDD) afflicts ~7% of reproductive age women resulting in impaired relationships, diminished overall quality of life, and disability-adjusted life years lost on par with other major psychiatric disorders. Response to pharmacological treatment is inadequate in ~50% of women with PMDD. OBJECTIVE: The goal of the present study is to evaluate the effects of a novel approach-short-term chromium supplementation-on menstrual cycle-related mood and physical symptoms. METHODS: Five women were studied under single-blind conditions in a private clinical setting (2 of them were referred specifically for treatment-resistant menstrual-related symptoms); 6 women completed a double blind crossover study of chromium plus placebo versus chromium plus sertraline in a university clinical research setting. Treatments were administered from mid cycle to onset of menses in 1-month intervals. Symptom ratings were obtained by self-report, using daily symptom checklists, and by clinical assessment, using the Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. RESULTS: Overall, chromium treatment was associated with reduced mood symptoms and improved overall health satisfaction in most participants. In some cases, chromium alone was associated with marked clinical improvement; in others, chromium plus an antidepressant resulted in greater improvement than either chromium alone or an antidepressant alone. CONCLUSION: These preliminary observations suggest that chromium may be a useful monotherapy or adjunctive therapy for women suffering from significant menstrual cycle-related symptoms. Larger, controlled studies are needed to evaluate the efficacy of chromium treatment in this patient population. PMID- 24237191 TI - An in vivo study examining the antiinflammatory effects of chamomile, meadowsweet, and willow bark in a novel functional beverage. AB - The antioxidant and antiinflammatory properties of polyphenols are well documented in vitro but there are few human studies. A herbal beverage composed of chamomile, meadowsweet, and willow bark (CMW) was developed and tested for its antiinflammatory effect in a cohort of healthy adults (n = 20) during a 4-week intervention. Subjects were randomised to either the treatment (TG) or placebo group (PG). The three herbs under study, which have been used in traditional and alternative medicine, were delivered in a berry extract matrix. This berry extract was used as a control in the experiment. The objective was to assess the herbs' effects on systemic inflammation and joint function by examining circulating cytokines and mechanical joint flexibility. Blood serum was analyzed for cytokines IL-1beta, IL-6, and TNFalpha. There was an average decrease of 21.7% IL-1beta in the treatment group, whereas the decrease seen in the placebo group was 3% but these were not statistically significant. Quartile analysis based on baseline production of TNFalpha demonstrated a decrease in the treatment group's IL-6 levels. This group showed improvements in mechanical joint function and pain upon movement of joints specific to the knee and lower back. Overall, no significant antiinflammatory effects were seen. The evidence is therefore inconclusive and further investigations are required using a larger cohort with some degree of elevated inflammatory activity. PMID- 24237192 TI - The CARE guidelines: consensus-based clinical case report guideline development. AB - BACKGROUND: A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. PRIMARY OBJECTIVE: Develop, disseminate, and implement systematic reporting guidelines for case reports. METHODS: We used a three-phase consensus process consisting of (a) pre-meeting literature review and interviews to generate items for the reporting guidelines; (b) a face-to-face consensus meeting to draft the reporting guidelines; and (c) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. RESULTS: This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. CONCLUSIONS: We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery. PMID- 24237193 TI - An evidence-based systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration. AB - An evidence-based systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. PMID- 24237194 TI - Optimization protocol for storage of goldfish (Carassius auratus) embryos in chilled state. AB - A series of five experiments were conducted to explore suitable conditions for storing of goldfish embryos in a chilled state. The factors studied were embryo stage, storage temperature, physiological saline solutions and goldfish artificial coelomic fluid (GFACF) medium, antibiotics (penicillin and streptomycin), antioxidants (vitamin E, vitamin C), buffer (Hepes, Tris) and BSA (bovine serum albumin). First, goldfish embryos at eight developmental stages were incubated in aerated and dechlorinated tap water at 0 degrees C for 24 h. Result shows that early developmental stages were most sensitive to chilling. Heartbeat-stage goldfish embryos were chilled at 0, 4 or 8 degrees C for up to 72 h in water, and chilled storage was possible only for up to 18, 24 and 48 h at 0, 4 and 8 degrees C, respectively, without a decrease in viability. Chilling of goldfish embryos at 8 degrees C in GFACF medium and Dettlaff's solution instead of water and other physiological saline solutions prolonged their viability (p < 0.01). Nevertheless, viability of chilled embryos in GFACF medium was slightly, but non-significantly, higher than in Dettlaff's solution. Supplementation of the GFACF medium with antibiotics, Hepes or BSA increased the viability of chilled embryos, but the tested vitamin E analogue Trolox, vitamin C or Tris concentration had no effect on embryo viability. The outcome of this series of experiments shows that heartbeat-stage goldfish embryos could be chilled for 60 h in GFACF supplemented with 25 mm Hepes, 100 U/ml penicillin, 10 MUg/l streptomycin and 1 g/l BSA in such a way that embryonic development does not proceed, and viability is not lost. PMID- 24237195 TI - High-throughput virtual screening identifies novel N'-(1-phenylethylidene) benzohydrazides as potent, specific, and reversible LSD1 inhibitors. AB - Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is an attractive therapeutic target in multiple malignancies. Here we report a structure-based virtual screen of a compound library containing ~2 million small molecular entities. Computational docking and scoring followed by biochemical screening led to the identification of a novel N'-(1-phenylethylidene) benzohydrazide series of LSD1 inhibitors with hits showing biochemical IC50s in the 200-400 nM range. Hit-to-lead optimization and structure-activity relationship studies aided in the discovery of compound 12, with a Ki of 31 nM. Compound 12 is reversible and specific for LSD1 as compared to the monoamine oxidases shows minimal inhibition of CYPs and hERG and inhibits proliferation and survival in several cancer cell lines, including breast and colorectal cancer. Compound 12 may be used to probe LSD1's biological role in these cancers. PMID- 24237196 TI - Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease. AB - 4-Hydroxy-2-nonenal (4-HNE), a reactive aldehyde, is generated from polyunsaturated fatty acids (PUFAs) in biological membranes. Reactive oxygen species (ROS) generated during oxidative stress react with PUFAs to form aldehydes like 4-HNE, which inactivates proteins and DNA by forming hybrid covalent chemical addition compounds called adducts. The ensuing chain reaction results in cellular dysfunction and tissue damage. It includes a wide spectrum of events ranging from electron transport chain dysfunction to apoptosis. In addition, 4-HNE directly depresses contractile function, enhances ROS formation, modulates cell signaling pathways, and can contribute to many cardiovascular diseases, including atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and cardiomyopathy. Therefore, targeting 4-HNE could help reverse these pathologies. This review will focus on 4-HNE generation, the role of 4-HNE in cardiovascular diseases, cellular targets (especially mitochondria), processes and mechanisms for 4-HNE-induced toxicity, regulation of 4-HNE metabolism, and finally strategies for developing potential therapies for cardiovascular disease by attenuating 4-HNEinduced toxicity. PMID- 24237197 TI - Expanding the cleft phenotype: the dental characteristics of unaffected parents of Australian children with non-syndromic cleft lip and palate. AB - BACKGROUND: The aetiology of isolated clefts of the lip and/or palate remains obscure. Unaffected family members are treated as if their genetic risks are equivalent and low. Given the number of genes associated with both clefting and dental anomalies, the hypothesis that such anomalies contribute to the cleft phenotype should be explored. AIM: To describe the dental characteristics of parents of children with non-syndromic cleft lip +/- palate. DESIGN: Unaffected parents of Australian children with a cleft of the lip +/- palate underwent dental examination including radiographs, photographs, and impressions. Dental anomalies were identified. RESULTS: Data were available on 101 parents (49 males, 52 females). Fifty-one participants had at least one dental anomaly. Twelve (11.8%) individuals had congenital absence of teeth, with seven missing multiple teeth. The tooth most commonly missing was the upper right lateral incisor. Five subjects (4.9%) had microdontia (upper lateral incisor most commonly affected). Four subjects (4.0%) had supernumerary teeth. Enamel defects were present in 27 (26.7%) cases with the incisors (46.8%) followed by premolars (24.2%) most affected. CONCLUSIONS: This study supports previous work suggesting that 'unaffected' parents of children with clefts of the lip +/- palate may present with dental anomalies. PMID- 24237198 TI - Are self-reported risk-taking behavior and helmet use associated with injury causes among skiers and snowboarders? AB - Over the last 10 years, ski helmet use has steadily increased worldwide. According to the "risk compensation theory," however, studies found that up to one third of skiers and snowboarders self-reported to engage in more risk taking when wearing a ski helmet. Therefore, to evaluate whether self-reported risk taking and ski helmet use affect accident causes on ski slopes, more than 2000 injured skiers and snowboarders were interviewed during the 2011/2012 winter season about accident causes and potential intrinsic and extrinsic risk factors. Chi-square tests revealed that ski helmet use did not significantly differ between self-reported risky and cautious people (81% vs 83%). Multivariate regression analysis revealed younger age groups [odds ratios (ORs) 1.8-1.9, P < 005], male sex (OR 2.4, P < 0.001), Austrian nationality (2.2, P < 0.001), higher skill level (1.7, P < 0.001), and off-slope skiing (OR 2.2, P = 0.060) to be predictive for a risky behavior on ski slopes. Neither the use of skis or snowboards nor accident causes were significantly associated with a riskier behavior on ski slopes. In conclusion, self-reported risk-taking behavior and ski helmet use seem not to be associated with accident causes leading to an injury among recreational skiers and snowboarders. PMID- 24237199 TI - From protein complexes to subunit backbone fragments: a multi-stage approach to native mass spectrometry. AB - Native mass spectrometry (MS) is becoming an important integral part of structural proteomics and system biology research. The approach holds great promise for elucidating higher levels of protein structure: from primary to quaternary. This requires the most efficient use of tandem MS, which is the cornerstone of MS-based approaches. In this work, we advance a two-step fragmentation approach, or (pseudo)-MS(3), from native protein complexes to a set of constituent fragment ions. Using an efficient desolvation approach and quadrupole selection in the extended mass-to-charge (m/z) range, we have accomplished sequential dissociation of large protein complexes, such as phosporylase B (194 kDa), pyruvate kinase (232 kDa), and GroEL (801 kDa), to highly charged monomers which were then dissociated to a set of multiply charged fragmentation products. Fragment ion signals were acquired with a high resolution, high mass accuracy Orbitrap instrument that enabled highly confident identifications of the precursor monomer subunits. The developed approach is expected to enable characterization of stoichiometry and composition of endogenous native protein complexes at an unprecedented level of detail. PMID- 24237202 TI - The concept of shared mental models in healthcare collaboration. AB - AIM: To report an analysis of the concept of shared mental models in health care. BACKGROUND: Shared mental models have been described as facilitators of effective teamwork. The complexity and criticality of the current healthcare system requires shared mental models to enhance safe and effective patient/client care. Yet, the current concept definition in the healthcare literature is vague and, therefore, difficult to apply consistently in research and practice. DESIGN: Concept analysis. DATA SOURCES: Literature for this concept analysis was retrieved from several databases, including CINAHL, PubMed and MEDLINE (EBSCO Interface), for the years 1997-2013. METHODS: Walker and Avant's approach to concept analysis was employed and, following Paley's guidance, embedded in extant theory from the team literature. RESULTS: Although teamwork and collaboration are discussed frequently in healthcare literature, the concept of shared mental models in that context is not as commonly found but is increasing in appearance. Our concept analysis defines shared mental models as individually held knowledge structures that help team members function collaboratively in their environments and are comprised of the attributes of content, similarity, accuracy and dynamics. CONCLUSION: This theoretically grounded concept analysis provides a foundation for a middle-range descriptive theory of shared mental models in nursing and health care. Further research concerning the impact of shared mental models in the healthcare setting can result in development and refinement of shared mental models to support effective teamwork and collaboration. PMID- 24237203 TI - Benzimidazole-based ratiometric two-photon fluorescent probes for acidic pH in live cells and tissues. AB - Many aspects of cell metabolism are controlled by acidic pH. We report a new family of small molecule and ratiometric two photon (TP) probes derived from benzimidazole (BH1-3 and BH1L) for monitoring acidic pH values. These probes are characterized by a strong two-photon excited fluorescence, a marked blue-to-green emission color change in response to pH, pKa values ranging from 4.9 to 6.1, a distinctive isoemissive point, negligible cytotoxicity, and high photostability, thereby allowing quantitative analysis of acidic pH. Moreover, we show that BH1L optimized as a lysosomal-targeted probe allows for direct, real-time estimation of the pH values inside lysosomal compartments in live cells as well as in living mouse brain tissues through the use of two-photon microscopy. These findings demonstrate that these probes will find useful applications in biomedical research. PMID- 24237204 TI - High-resolution secondary ion mass spectrometry analysis of carbon dynamics in mycorrhizas formed by an obligately myco-heterotrophic orchid. AB - Mycorrhiza formation represents a significant carbon (C) acquisition alternative for orchid species, particularly those that remain achlorophyllous through all life stages. As it is known that orchid mycorrhizas facilitate nutrient transfer (most notably of C), it has not been resolved if C transfer occurs only after lysis of mycorrhizal structures (fungal pelotons) or also across the mycorrhizal interface of pre-lysed pelotons. We used high-resolution secondary ion mass spectrometry (nanoSIMS) and labelling with enriched (13) CO2 to trace C transfers, at subcellular scale, across mycorrhizal interfaces formed by Rhizanthella gardneri, an achlorphyllous orchid. Carbon was successfully traced in to the fungal portion of orchid mycorrhizas. However, we did not detect C movement across intact mycorrhizal interfaces up to 216 h post (13) CO2 labelling. Our findings provide support for the hypothesis that C transfer from the mycorrhizal fungus to orchid, at least for R. gardneri, likely occurs after lysis of the fungal peloton. PMID- 24237205 TI - Time of change within the journal. PMID- 24237206 TI - Are waves of relational assumptions eroding traditional analysis? AB - The author designates as 'traditional' those elements of psychoanalytic presumption and practice that have, in the wake of Fordham's legacy, helped to inform analytical psychology and expand our capacity to integrate the shadow. It is argued that this element of the broad spectrum of Jungian practice is in danger of erosion by the underlying assumptions of the relational approach, which is fast becoming the new establishment. If the maps of the traditional landscape of symbolic reference (primal scene, Oedipus et al.) are disregarded, analysts are left with only their own self-appointed authority with which to orientate themselves. This self-centric epistemological basis of the relationalists leads to a revision of 'analytic attitude' that may be therapeutic but is not essentially analytic. This theme is linked to the perennial challenge of balancing differentiation and merger and traced back, through Chasseguet-Smirgel, to its roots in Genesis. An endeavour is made to illustrate this within the Journal convention of clinically based discussion through a commentary on Colman's (2013) avowedly relational treatment of the case material presented in his recent Journal paper 'Reflections on knowledge and experience' and through an assessment of Jessica Benjamin's (2004) relational critique of Ron Britton's (1989) transference embodied approach. PMID- 24237207 TI - On the impact of words: interpretation, empathy and affect regulation. AB - This paper offers a contribution towards furthering our understanding of a theme more usually associated with the Freudian tradition, namely the role and function of words as action, particularly in relation to the representational process and its somatic roots. Some reference to neuroscience research will be offered in this respect. It also considers the value of differentiating Empathy from Empathism, as defined by the Italian psychoanalyst Stefano Bolognini who distinguishes informing complementary countertransference from states of over concordance. Two analytic sessions taken from the intensive analysis of a deeply deprived late-latency child showing violent behaviour are provided with the aim of illustrating the application of these concepts. It is argued that, given the same elaboration of the countertransference and the adequate empathic position on the part of the analyst, the difference in the outcome of the interpretation was made by the specific use of words-in this case the use or not of the personal pronoun-in the two sessions. As the case material is taken from the clinical work of a supervisee, some elements regarding the supervisory situation are also discussed in the paper. PMID- 24237208 TI - Out of the body: embodiment and its vicissitudes. AB - Body-mind dualism and the consequent neglect of the body of the analyst can have important negative effects on the analytical process leading all too often to misinterpretations of the analysand's verbal and non-verbal communications and to disturbances of analytical temporality. This is intensified when we are dealing with individuals where disembodiment and states of psychic deadness are central features. The paper explores the philosophical roots of the idea of a disembodied mind and the way in which this impacts our relationship with the world. While Andre Green's concept of the dead mother and disturbances in the sense of self agency have been held to play an important role in states of psychic deadness, I suggest that it is rather disturbances in the sense of body ownership and of the body image which are more central. The paper then discusses the particular kinds of countertransference that can be evoked in the analyst when we find ourselves dealing with this type of patient and suggests how we can use our embodied countertransference to become aware of and elaborate our own feelings of deadness in order to overcome the loss of temporality that is characteristic of such states. This is illustrated with reference to my work with a young man with a masochistic perversion and a severe disturbance of the body image with an accompanying profound sense of psychic deadness. PMID- 24237209 TI - The King of Norway: negative individuation, the hero myth and psychopathic narcissism in extreme violence and the life of Anders Behring Breivik. AB - The paper discusses negative individuation and the hero myth as developmental concepts. It is suggested that in negative individuation healthy psychological development is hindered and goes astray. Aggression then becomes the central psychic system. Repressed anger is the core element in psychopathic narcissism (Diamond) and malignant narcissism (Kernberg). Both Diamond and Kernberg extend narcissistic personality structure to antisocial, psychopathic personality in an effort to better understand extreme violence. According to Freud, love (libido) and hate (the death drive) are the major motivational systems in the human psyche. In contrast to Freud, Jung sees libido as a life force in general, not simply as a sexual drive. Jung writes about evil and the shadow but does not present a comprehensive theory of the negative development of an individual's life. The concept of negative individuation connects the shadow and the death drive with psychopathology, psychiatry and psychotherapy. In this paper, I explore these concepts in the light of contemporary affect theory according to Kernberg. I also ask how ideology is tied to extreme violence and how it is possible that narcissistic personality structures can lead to such radically different outcomes as were manifested in the lives of Anders Behring Breivik and Steve Jobs. PMID- 24237210 TI - James Astor in conversation with Warren Colman. AB - In this interview with Warren Colman, James Astor speaks about his development as a Jungian analyst from his own experience of personal analysis in the 1960s to his recent retirement from clinical practice. The discussion covers his long association with Michael Fordham, the child analytic training at the SAP, the infant observation seminars with Fordham and Gianna Henry through which Fordham was able to make new discoveries about infant development, his experience of supervision with Donald Meltzer and the development of his own thinking through a series of papers on the analytic process, supervision and the relation between language and truth. The interview concludes with reflections about the legacy of Michael Fordham and the future of analytic work. PMID- 24237216 TI - Editorial: Cancer immunotherapy: does an increasing arsenal of tools point to more fruitful avenues for research? PMID- 24237217 TI - Therapeutic vaccines explored in patients with non-small cell lung cancer. AB - Traditional anti-cancer therapies (surgery, radiotherapy and chemotherapy) have limited effectiveness in curbing progression of advanced tumors. However, with advances in immunology and molecular biology in the last two decades, the prognosis of cancer immunotherapy has improved. An emerging therapy is the cancer vaccine as adjunctive therapy. The purpose of this paper is to review this therapeutic modality for non-small cell lung cancer. PMID- 24237218 TI - HPV-specific immunotherapy: key role for immunomodulators. AB - Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic. PMID- 24237219 TI - Poxvirus-based vaccines for cancer immunotherapy: new insights from combined cytokines/co-stimulatory molecules delivery and "uncommon" strains. AB - Poxvirus-based vaccines have a long record of efficacy as both anti-tumour agents and vectors for gene therapy in different human tumour models. Interestingly, several studies of these vaccines have now entered the clinical evaluation phase for safety and effectiveness. A desirable outcome of antigen specific cancer immunotherapy is the disruption of host self-tolerance against endogenous tumour associated antigens (TAAs). Nonetheless, recent studies have found reductions in vaccine efficacy due to host anti-vaccine immune reactions. Thus, newer approaches bringing together poxvirus-based vaccination and immunostimulation are being developed, and new poxvirus strains are being examined in tumour therapy studies. Our review summarizes the current knowledge on the efficacy of poxvirus based vaccination on human tumours, with a particular focus on approaches aimed at increasing innate and specific immune responses. Special attention will be devoted to the new poxvirus strains that are currently under consideration for tumour therapy; the current knowledge on clinical trials and outcomes will also be reviewed. PMID- 24237220 TI - CCL21 and IFNgamma recruit and activate tumor specific T cells in 3D scaffold model of breast cancer. AB - Effective elicitation of endogenous immunity is associated with improved prognosis for cancer patients. Clinical evidence in hematological and solid cancers shows that intratumoral injection of immunostimulatory genes primes and augments endogenous T cell responses. The ability of pro-inflammatory chemokines/cytokines to facilitate migration/activation of antigen-presenting cells (APC) and lymphocytes prompted our modeling of intratumoral delivery of a chemokine/cytokine combination for breast cancer treatment. Here, we demonstrate that expression of chemokine ligand 21 (CCL21) and interferon gamma (IFNgamma) in tumors improves tumor specific T cell recruitment to tumor and activation in the tumor milieu. IFNgamma and CCL21 were delivered into tumor cells via plasmids, and transfected cells were seeded to form spheroids on three-dimensional (3D) chitosan-alginate (CA) scaffolds. Co-expression of CCL21 and IFNgamma, as evidenced by qRT-PCR and ELISA, induced increased recruitment, binding, and infiltration of anti-neu (p98) peptide specific T cells into the breast tumors as determined by SEM and immunofluorescence assays. The co-expression promoted recruitment of only p98 T cells, but not naive T cells, demonstrating an antigen restricted activation. Furthermore, the co-expression impacted T helper (Th) cell immunity, promoting an increase in secretion of pro-inflammatory Th-associated cytokine, tumor necrosis factor alpha (TNFalpha), and cytotoxic T lymphocyte (CTL)-associated protease, Granzyme B (GzB). Therefore, 3D CA scaffolds may be a useful breast cancer tumor microenvironment model to evaluate T cell function. Further characterization of CCL21-IFNgamma mediated anti-tumor immunity will potentially benefit the development of chemokine/cytokine combination platforms as anti-cancer agents. PMID- 24237222 TI - Application of dsRNA in cancer immunotherapy: current status and future trends. AB - Cancer cells create a microenvironment that prevents tumor rejection by the host's immune system. The activation of pattern recognition receptors (PRRs) can elicit an innate immune response and guide the adaptive immune response to overcome this. dsRNA analogs can trigger TLR3, RIG-I, MDA5, NLRP3 and several other PRRs to induce not only robust immune response against cancer but also programmed cell death. This review focuses on the signal pathways activated by dsRNA and examines examples of their clinical application in cancer treatment. PMID- 24237221 TI - Chemical metabolic inhibitors for the treatment of blood-borne cancers. AB - Tumor cells, including leukemic cells, remodel their bioenergetic system in favor of aerobic glycolysis. This process is called "the Warburg effect" and offers an attractive pharmacological target to preferentially eliminate malignant cells. In addition, recent results show that metabolic changes can be linked to tumor immune evasion. Mouse models demonstrate the importance of this metabolic remodeling in leukemogenesis. Some leukemias, although treatable, remain incurable and resistance to chemotherapy produces an elevated percentage of relapse in most leukemia cases. Several groups have targeted the specific metabolism of leukemia cells in preclinical and clinical studies to improve the prognosis of these patients, i.e. using L-asparaginase to treat pediatric acute lymphocytic leukemia (ALL). Additional metabolic drugs that are currently being used to treat other diseases or tumors could also be exploited for leukemia, based on preclinical studies. Finally, we discuss the potential use of several metabolic drugs in combination therapies, including immunomodulatory drugs (IMiDs) or immune cell-based therapies, to increase their efficacy and reduce side effects in the treatment of hematological cancers. PMID- 24237223 TI - The need for improvement of the treatment of advanced and metastatic cervical cancer, the rationale for combined chemo-immunotherapy. AB - The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. The last decades, targeted therapies such as immunotherapy have emerged as an attractive option for the treatment of these patients. Immunotherapy can consist of different modalities such as monoclonal antibodies, adoptive lymphocyte transfer and vaccines, which all are intended to augment the antitumor immune responses in cancer patients. The available evidence indicates that both active and adoptive immunotherapeutical strategies are quite effective against small tumor burdens, but are usually insufficient to eradicate the disease in patients with advanced stages of different kinds of cancer, despite strong induction of tumor-specific immune responses. Although chemotherapy and immunotherapy have not shown to be curative as single modalities, accumulating evidence suggests that combinations of these treatments hold potential for improved clinical outcomes in advanced stages of cancer. Therefore, the combination of chemotherapy and immunotherapy is no longer considered incompatible, because of the emerging insight that certain chemotherapy-based cancer treatments may activate the immune system against the tumor through several molecular and cellular mechanisms. Chemotherapeutic agents and immunotherapy may thus be synergistic and enhance the clinical response. In this review, we show the rationale for combined chemo-immunotherapeutic strategies, and summarize recent data from clinical trials performed in patients with different types of cancer. Challenges such as the selection of the optimal dose and treatment schedule, will be discussed as well as the identification of immune-specific biomarkers. Furthermore, we evaluated the long-term clinical outcomes of patients with advanced cervical cancer treated with HPV16 E6/E7 SLP vaccination with or without chemotherapy. Finally, the future of vaccination therapy in combination with chemotherapy for the treatment of cervical cancer is discussed. PMID- 24237224 TI - Ex vivo-activated MHC-unrestricted immune effectors for cancer adoptive immunotherapy. AB - Adoptive immunotherapy is considered a promising strategy for the treatment of metastatic tumors and current research efforts are directed to define the optimal approach and facilitate the transferability from preclinical to clinical settings. Among several approaches it is possible to schematically distinguish strategies based on either MHC-restricted or MHC-unrestricted immune effectors. The first are mainly based on the infusion of tumor-specific T lymphocytes capable of recognizing determined MHC-restricted tumor associated antigens (TAA) through their T cell receptor. MHC-unrestricted approaches do not target specific tumor associated antigens and are mainly mediated by effectors of the innate immune system, like natural killer (NK) cells or NKT cells, first barrier against pathogens and tumorigenesis processes, or by ex vivo activated lymphocytes like cytokine-induced killer (CIK) cells. MHC-unrestricted effectors are usually more abundant than TAA-specific precursors and easier to expand. Furthermore their activity is not restricted to precise HLA-haplotypes, not limited to a single tumor histotype and could overcome downregulation of MHC molecules operated by tumor cells as immune escape mechanism. In this review we will discuss the main cancer immunotherapy strategies based on MHC-unrestricted immune effectors. The topic will be approached from the angle of ex vivo expansion protocols in clinical prospective, as well as potential approaches to favorably modulate their functions. PMID- 24237227 TI - Submucous Cleft Palate: A Systematic Review of Surgical Management Based on Perceptual and Instrumental Analysis. AB - Objective: Submucous cleft palate (SMCP) is a congenital condition associated with abnormal development of the soft palate musculature. In a proportion of cases, this results in velopharyngeal insufficiency (VPI), the treatment for which includes pharyngeal flap surgery, pharyngoplasty, and palate reconstruction. The aim of this paper is to determine whether there is superiority of one or more types of surgical procedure over the others in improving speech in patients with VPI secondary to SMCP. Methodology: Nine databases, including MEDLINE and EMBASE, were searched between inception and January 2013 to identify articles published relating to the surgical management of SMCP. Only studies that reported outcome measures for postoperative speech were included in the systematic review. Results: Twenty-six studies analyzing the outcomes of surgery for VPI in patients with SMCP met the inclusion criteria. In these studies, speech outcomes were measured either in a binary fashion (i.e., normal speech or evidence of VPI) or using scales of VPI severity. Of the 26 studies, only two utilized blinded speech assessment, and 12 included both preoperative and postoperative speech assessment. Conclusions: The review found little evidence to support any specific surgical intervention. This is in large part due to the inclusion of mixed etiologies within study populations and the lack of unbiased validated preoperative and postoperative speech assessment. Further methodologically rigorous studies need to be conducted to provide a secure evidence base for the surgical management of SMCP. PMID- 24237226 TI - Congenital platelet disorder and type I von Willebrand disease presenting as prolonged bleeding after cleft lip and palate repair. AB - Cleft lip and palate can be associated with coagulopathy. Here, we report the first known case of congenital platelet disorder and von Willebrand disease presenting as prolonged bleeding after cleft lip and palate repair. After identifying the underlying pathology, platelet infusions and aminocaproic acid were given to decrease bleeding from a second surgical procedure. Whole exome sequencing identified a von Willebrand factor gene mutation, an adenine to guanine substitution at the c.475A location. A high index of suspicion should be had for coagulopathy in patients with syndromic cleft lip and palate. PMID- 24237225 TI - The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention. AB - Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of garlic reveal conflicting data as to pro- or anti inflammatory responses depending on the particular experimental set-ups and the garlic preparation used (i.e. garlic extract versus chemically pure garlic compounds). Here we provide an overview of the chemistry of the major garlic organosulfur compounds, summarize the current understanding and propose a link between the immunomodulating activity of garlic and the prevention of cancer. We hypothesize that garlic rather elicits anti-inflammatory and anti-oxidative responses that aid in priming the organism towards eradication of an emerging tumor. PMID- 24237228 TI - CPCJ 50th Anniversary Editorial Board Commentary: Ethics and Health Policy-Then and Now. AB - To celebrate the 50th year of the Cleft Palate-Craniofacial Journal we look back to where we started in 1964, where we are now, and speculate about directions for the future in a Then and Now editorial series. This editorial examines 50 years of social, policy, and regulatory changes that broaden the responsibility for research integrity to include the investigator, the journal editorial review process, and institutional oversight. Internationally recognized standards for authorship, publication of recognizable cases and images, and confidentiality of peer-review are addressed in the context of the history of the CPCJ. As we look to the future, the core principles will continue to guide the endeavor of research involving human subjects while adhering to our obligations to protect the interests of the people we serve. PMID- 24237229 TI - Otitis media with effusion: experiences of children with cleft palate and their parents. AB - OBJECTIVE: To explore the views of children with cleft palate and their parents about daily life with otitis media with effusion and associated hearing loss. DESIGN: A qualitative study. Semistructured interviews were used to collect data from parents. Participatory techniques, including activities on a tablet computer, were used to collect data from children. Framework analysis was applied to interview transcripts. SETTING: Two English cleft units. PARTICIPANTS: A purposive sample of parents of 37 children aged 0 to 11 years with experience of otitis media with effusion. Their children also took part if aged 6 to 11 years (n = 22). RESULTS: Themes related to the following: (1) emotions (frustration, anger, sadness, happiness, anxiety), (2) educational experiences (struggling at school, having to sit at the front of the class, requiring extra support, missing lessons for appointments or due to ear infections), (3) social interactions (isolation, communication, reliance on siblings, participation in activities). CONCLUSIONS: A number of areas of interviewees' everyday life were affected by the presence of otitis media with effusion. Parents may need to be forewarned about the possible ongoing nature of this condition and its impact on a child's social and emotional experiences. Children may also benefit from age-appropriate information about otitis media with effusion and its treatment, including information on hearing tests, to help reduce any anxiety. PMID- 24237230 TI - Mechanical model of vertical nanowire cell penetration. AB - Direct access into cells' interiors is essential for biomolecular delivery, gene transfection, and electrical recordings yet is challenging due to the cell membrane barrier. Recently, molecular delivery using vertical nanowires (NWs) has been demonstrated for introducing biomolecules into a large number of cells in parallel. However, the microscopic understanding of how and when the nanowires penetrate cell membranes is still lacking, and the degree to which actual membrane penetration occurs is controversial. Here we present results from a mechanical continuum model of elastic cell membrane penetration through two mechanisms, namely through "impaling" as cells land onto a bed of nanowires, and through "adhesion-mediated" penetration, which occurs as cells spread on the substrate and generate adhesion force. Our results reveal that penetration is much more effective through the adhesion mechanism, with NW geometry and cell stiffness being critically important. Stiffer cells have higher penetration efficiency, but are more sensitive to NW geometry. These results provide a guide to designing nanowires for applications in cell membrane penetration. PMID- 24237231 TI - Compulsory licensing issues and trends in Asia. PMID- 24237232 TI - Compulsory pharmaceutical patent licensing in Brazil: the controversy of public interest. PMID- 24237233 TI - Writing a good patent application. PMID- 24237234 TI - South Africa pushes new IP policy. PMID- 24237235 TI - Insights into the role of patents in R&D. AB - Pharmaceutical Patent Analyst has called on a group of international experts to explore key themes relating to intellectual property within the context of the fields of medical and pharmaceutical science. Topics include a reflection on how worrying the patent cliff really is, and adapting to life beyond it; to the ways in which social media is affecting how lawyers share information, and steps for protecting IP against the risks posed by hacking and cybersurveillance. We hope you enjoy these insightful contributions. Commissioned and edited by Gino D'Oca, Head of Commissioning. PMID- 24237238 TI - The skilled person: an evolving concept. AB - The skilled person is a concept central to patent law, underpinning the analysis of obviousness, sufficiency, claim construction, novelty, added matter and priority. Identifying such a person correctly, particularly the level of skill and the common general knowledge that they should possess, is critical to determining whether a patent is valid and/or infringed and has significant implications for the pharmaceutical industry. However, the concept can be difficult to define. Once referred to as 'The man on the Clapham omnibus' of patent law, the skilled person is a technician who is skilled in the art yet wholly devoid of imagination. Nevertheless, his attributes and knowledge, which are context-dependent and vary from art to art, are continually evolving. This article will look at the evolution of the skilled person, focusing on the implications for the future of pharmaceutical patents and patent litigation. PMID- 24237239 TI - Evergreening by whom? A review of secondary patents for omeprazole. AB - Evergreening, or the practice of technology developers to retain legal protection over valuable drugs beyond the normal patent term, is a well known practice by originators of successful drugs. Generic competitors also attempt similar strategies for commercial reasons. In this paper we look at secondary US and European patents in relation to the 'blockbuster' drug omeprazole (e.g., Prilosec(r) by AstraZeneca among other brands), with these secondary patents selected because they refer to the 'omeprazole' in either the title, abstract, Derwent Title or first claim. We find that 485 patents meet this criteria, with only 29% owned by the drugs originator (or known subsidiaries or predecessors). AstraZeneca was also the leading applicant by a number of measures, including grant ratio, number of patents filed, forward citation count, family member count and claim breadth. PMID- 24237240 TI - Patented nanomedicines for the treatment of brain tumors. AB - Patients affected by malignant brain tumors present an extremely poor prognosis, notwithstanding improvements in surgery techniques and therapeutic protocols. Brain tumor treatment has been principally hampered by limited drug delivery across the blood-brain barrier (BBB). An efficacious chemotherapeutic treatment requires a pharmacological agent that can penetrate the BBB and target neoplastic cells. Nanotechnology involves the design, synthesis and characterization of materials that have a functional organization in at least one dimension on the nanometer scale. Nanoparticle systems can represent optimal devices for delivery of various drugs into the brain across the BBB. Nanoparticle drug-delivery systems can also be used to provide targeted delivery of drugs, improve bioavailability and sustain release of drugs for systemic delivery. In this patent review, the recent studies of certain nanoparticle systems in treatment of brain tumors are summarized. Common nanoparticles systems include polymeric nanoparticles, lipid nanoparticles and inorganic nanoparticles. Various patents of nanoparticle systems able to across the BBB to target brain tumors are also reported and discussed. PMID- 24237241 TI - Discussion of PARP inhibitors in cancer therapy. AB - Poly (ADP-ribose) polymerases (PARP) are a family of enzymes that play a very important role in preserving the integrity of the genome. Recently, PARP inhibitors have been shown to enhance the therapeutic ratio in cancer patients due to their specific targeting of homologous recombination repair-defective tumors, through a synthetic lethal interaction. Researchers are also presently investigating novel strategies for the treatment of sporadic cancers by combining PARP inhibitors with other DNA-damaging agents. This review will focus on recently patented PARP inhibitors and literature that supports the reported claims presented in these patents. The patents reviewed were categorized into two groups: PARP inhibitors as a single-agent or in combination with other agents for the treatment of various types of cancer. These compounds are currently in clinical trials and, if successful, can greatly impact therapeutic index in cancer therapy. PMID- 24237242 TI - Metabotropic glutamate receptor 5-negative allosteric modulators for the treatment of psychiatric and neurological disorders (2009-July 2013). AB - Negative allosteric modulators of metabotropic glutamate receptor 5 (mGlu5) have been actively pursued for over a decade as a potential treatment for anxiety, depression, substance abuse, pain, levodopa-induced dyskinesia in Parkinson's disease, fragile X Syndrome, autism, gastroesophageal reflux disease and lower urinary-tract disorders. This article begins with an introduction of preclinical validation of potential therapies for psychiatric and neurological disorders, and of clinical results, followed by a comprehensive overview of the mGlu5-negative allosteric modulator patent applications published between 2009 and July 2013, with a focus on the analysis of structure and in silico CNS drug-like properties of example compounds and disclosed data. Given positive results in proof-of concept studies in humans for certain indications such as levodopa-induced dyskinesia in Parkinson's disease, fragile X Syndrome, gastroesophageal reflux disease, migraine and anxiety, and the soaring chemical diversity among the mGlu5 negative allosteric modulators, there is reason to believe that a drug will emerge from this therapeutic class in the near future. PMID- 24237244 TI - Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus. AB - AIM: Type 1 diabetes mellitus (T1DM) increases fragility fractures due to low bone mass, micro-architectural alterations and decreased bone formation. Sclerostin is expressed by osteocytes and inhibits osteoblastic bone formation. We evaluated serum sclerostin levels in T1DM and their association with bone mineral density (BMD), bone turnover, glycaemic control and physical activity. PATIENTS AND METHODS: In a cross-sectional study, 128 men and premenopausal women with long-standing T1DM (mean age 43.4 +/- 8.8 years, diabetes duration 22.4 +/- 9.5 years) and 77 age-, BMI (Body Mass Index) and gender-matched healthy individuals were evaluated. RESULTS: Serum sclerostin levels were higher in T1DM compared with controls, irrespective of gender (male 0.55 +/- 0.17 vs 0.49 +/- 0.12 ng/ml, P = 0.046; female 0.52 +/- 0.19 ng/ml vs 0.43 +/- 0.12 ng/ml, P = 0.012). Partial correlation analysis adjusted for age and gender revealed a positive correlation between serum sclerostin levels and BMD at lumbar spine and femoral neck in T1DM and between BMD at lumbar spine, femoral neck and total hip in controls. Bone turnover markers, parathyroid hormone, calcium and vitamin D did not correlate with serum sclerostin levels in T1DM or controls. Physical activity was not associated with serum sclerostin levels. A multivariate analysis revealed that only the interaction of T1DM and age affects serum sclerostin levels but not T1DM alone. The influence of age on serum sclerostin levels was more pronounced in T1DM compared with controls. CONCLUSIONS: Sclerostin serum levels were increased in patients with T1DM, and the positive correlation of age with serum sclerostin levels was stronger in T1DM. There was no effect of serum sclerostin levels on markers of bone metabolism and they do not explain the detrimental effects of T1DM on BMD. PMID- 24237245 TI - Radiation of the Nod-independent Aeschynomene relies on multiple allopolyploid speciation events. AB - * The semi-aquatic legumes belonging to the genus Aeschynomene constitute a premium system for investigating the origin and evolution of unusual symbiotic features such as stem nodulation and the presence of a Nod-independent infection process. This latter apparently arose in a single Aeschynomene lineage. But how this unique Nod-independent group then radiated is not yet known. * We have investigated the role of polyploidy in Aeschynomene speciation via a case study of the pantropical A. indica and then extended the analysis to the other Nod independent species. For this, we combined SSR genotyping, genome characterization through flow cytometry, chromosome counting, FISH and GISH experiments, molecular phylogenies using ITS and single nuclear gene sequences, and artificial hybridizations. * These analyses demonstrate the existence of an A. indica polyploid species complex comprising A. evenia (C. Wright) (2n = 2x = 20), A. indica L. s.s. (2n = 4x = 40) and a new hexaploid form (2n = 6x = 60). This latter contains the two genomes present in the tetraploid (A. evenia and A. scabra) and another unidentified genome. Two other species, A. pratensis and A. virginica, are also shown to be of allopolyploid origin. * This work reveals multiple hybridization/polyploidization events, thus highlighting a prominent role of allopolyploidy in the radiation of the Nod-independent Aeschynomene. PMID- 24237246 TI - A novel method for the immobilization of a thermostable fungal chitinase and the properties of the immobilized enzyme. AB - The recombinant thermostable fungal chitinase of Thermomyces lanuginosus was immobilized on the phenyl Sepharose matrix, and the properties of the immobilized chitinase were studied. The immobilized enzyme was optimally active at pH 6.0 and 50 degrees C and showed improved activity in the acidic range of pH values when compared with the soluble enzyme. The recombinant thermostable immobilized enzyme showed remarkable thermostability at 50 degrees C by retaining about 45% of the activity for more than 6 H. The KM and Vmax values were 1.3 mM and 4.5 mol/min/mg of protein, respectively. Both the free and immobilized forms of the enzymes were inhibited significantly by Ag(+) but behaved similarly to various other metal ions, detergents, and additives. The immobilized enzyme was stable for at least 1 month at 4 degrees C. PMID- 24237247 TI - Long-term survival in horses with strangulating obstruction of the small intestine managed without resection. AB - REASONS FOR PERFORMING STUDY: Although many studies have described results after small intestinal resection and anastomosis in horses, few have described the outcome in horses with strangulating lesions managed without resection. OBJECTIVES: To examine short- and long-term recoveries in horses with strangulated small intestine that was judged to be viable during surgery and not resected. STUDY DESIGN: Retrospective analysis of case records. METHODS: Data were reviewed from all cases (35 horses) with colic caused by small intestinal strangulation that underwent surgery between 1996 and 2011 at 2 university hospitals and that were managed without resection by 2 surgeons who used a clinical grading system to assess intestinal viability. Kaplan-Meier analyses were used to examine long-term survival. RESULTS: Survival to discharge from the hospital was 100%, and post operative complications developed in 11 horses (31%). Three horses (8.6%) required repeat coeliotomy because of persistent pain with or without reflux, and they responded favourably to decompression of distended intestine. Ten horses died after discharge, and 12 were still alive at follow-up from 20 to 192 months after surgery. Information was available on 13 horses after discharge, but these were eventually lost to follow-up. Kaplan-Meier analyses yielded a median survival probability of 120 months. CONCLUSIONS: A subjective method of assessing small intestinal viability in strangulated small intestine in horses, as used in this study, could reduce the need for resection and anastomosis, with the associated complications and costs. Also, the favourable post operative course in these horses provides strong evidence that early referral could avoid the need for resection and improve survival. The numbers of horses with the most severe changes that were not resected were too small to allow a conclusion that such segments should be left in place, and additional criteria might be needed to guide that decision in such cases. PMID- 24237248 TI - Self-assembly of nanoparticle arrays for use as mirrors, sensors, and antennas. AB - The self-assembly of nanoparticles (NPs) at liquid-liquid interfaces (LLIs) has recently emerged as a promising platform for tunable optical devices, sensors, and catalysis. There are numerous advantages for such platforms when compared to more conventional solid-state counterparts. For example, they do not need engineering, self-assemble if proper conditions are provided, are self-healing, are practically nondegrading, and are easily renewable. Furthermore, they have the added benefit of being able to facilitate the interactions of analytes dissolved in often-inaccessible environments. In this Perspective, we highlight some important recent developments in understanding the mechanisms and applications of self-assembly of NPs at LLIs for use as mirrors and sensors. Finally, we explore future directions in this field, focusing on NP arrays with electrotunable properties assembled at a LLI, which has been one of the driving forces for developing such technologies. PMID- 24237249 TI - Life cycle assessment of vehicle lightweighting: a physics-based model of mass induced fuel consumption. AB - Lightweighting is a key strategy used to improve vehicle fuel economy. Replacing conventional materials (e.g., steel) with lighter alternatives (e.g., aluminum, magnesium, and composites) decreases energy consumption and greenhouse gas (GHG) emissions during vehicle use, but often increases energy consumption and GHG emissions during materials and vehicle production. Assessing the life-cycle benefits of mass reduction requires a quantitative description of the mass induced fuel consumption during vehicle use. A new physics-based method for estimating mass-induced fuel consumption (MIF) is proposed. We illustrate the utility of this method by using publicly available data to calculate MIF values in the range of 0.2-0.5 L/(100 km 100 kg) based on 106 records of fuel economy tests by the U.S. Environmental Protection Agency for 2013 model year vehicles. Lightweighting is shown to have the most benefit when applied to vehicles with high fuel consumption and high power. Use of the physics-based model presented here would place future life cycle assessment studies of vehicle lightweighting on a firmer scientific foundation. PMID- 24237250 TI - Enhancing effects of electron-withdrawing groups and metallic ions on halogen bonding in the YC6F4X...C2H8N2 (X = Cl, Br, I; Y = F, CN, NO2, LiNC+, NaNC+) complex. AB - Halogen-bonding interactions are highly directional intermolecular interactions that are often important in crystal engineering. In this work, the second-order Moller-Plesset perturbation theory (MP2) calculations and the quantum theory of "atoms in molecules" (QTAIM) and noncovalent interaction (NCI) studies were carried out on a series of X...N halogen bonds between substituted haloperfluoroarenes C6F4XY (X = Cl, Br, I; Y = F, CN, NO2) as bond donors and 1,2 diaminoethane as bond acceptor. Our research supports earlier work that electron withdrawing substituents produce an enhancement effect on the size of the sigma hole and the maximum positive electrostatic potentials (VS,max), which further strengthens the halogen bonding. The metallic ion M(+) (M(+) = Li(+), Na(+)) has the ability to enhance the size of both the sigma-hole and VS,max value with the formation of [MNCC6F4X](+), resulting in more electronic charge transfer away from the halogen atom X and an increase in the strength of the halogen bond. It is found that the values of V(S,max) at the sigma-holes are linear in relation to the halogen-bonded interaction energies and the halogen-bonding interaction distance, indicating that the electrostatic interaction plays a key role in the halogen-bonding interactions. The values of V(S,max) at the sigma-holes are also linear in relation to the electron density rho(b), its Laplacian nabla(2)rhob, and -Gb/Vb of XB, indicating that the topological properties (rhob, nabla(2)rhob) and energy properties (Gb, Vb) at the BCPs are correlated with the electrostatic potentials. PMID- 24237251 TI - Evolution of a genetic diagnosis. AB - Understanding the relationship between genotype and phenotype has become an integral part of the diagnosis and management of patients with inherited arrhythmias and cardiomyopathies. Given the existence of background noise, the majority of genetic testing results should be incorporated into clinical decision making as probabilistic, rather than deterministic, in the diagnosis and management of inherited arrhythmias. This case report captures multiple snapshots of clinical care in the evolution of a diagnosis of a single patient, highlighting the need for repeated phenotypic and genotypic assessment for both the patient and their family. PMID- 24237252 TI - Comparative effects of pulsatile and nonpulsatile flow on plasma fibrinolytic balance in pediatric patients undergoing cardiopulmonary bypass. AB - In the brain, the components of the fibrinolytic system, tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1), regulate various neurophysiological and pathological responses. Fibrinolytic balance depends on PAI-1 and tPA concentrations. The objective of this study is to compare the effects of pulsatile and nonpulsatile perfusion on fibrinolytic balance in children undergoing pediatric cardiopulmonary bypass (CPB). Plasma PAI-1 antigen and tPA antigen were measured in 40 children (n = 20 pulsatile and n = 20 nonpulsatile group). Plasma samples (1.5 mL) were collected (i) prior to incision, (ii) 1 h after CPB, and (iii) 24 h after CPB. PAI-1 and tPA levels were measured at each time point. PAI-1 and tPA levels were significantly increased at 1 h after CPB, followed by a decrease at 24 h. Nonpulsatile but not pulsatile CPB lowered PAI-1 : tPA ratio significantly at 24 h (median PAI-1 : tPA ratio 4.63 +/- 0.83:1.98 +/- 0.48, P = 0.03, for the nonpulsatile group and 4.50 +/- 0.92:3.56 +/- 1.28, P = 0.2, for the pulsatile group). These results suggest that pulsatile flow maintains endogenous fibrinolytic balance after pediatric cardiopulmonary bypass. Further studies are needed to define the clinical significance of these differences. PMID- 24237253 TI - Erythroid and megakaryocytic differentiation of K562 erythroleukemic cells by monochloramine. AB - The induction of leukemic cell differentiation is a hopeful therapeutic modality. We studied the effects of monochloramine (NH2Cl) on erythroleukemic K562 cell differentiation, and compared the effects observed with those of U0126 and staurosporine, which are known inducers of erythroid and megakaryocytic differentiation, respectively. CD235 (glycophorin) expression, a marker of erythroid differentiation, was significantly increased by NH2Cl and U0126, along with an increase in cd235 mRNA levels. Other erythroid markers such as gamma globin and CD71 (transferrin receptor) were also increased by NH2Cl and U0126. In contrast, CD61 (integrin beta3) and CD42b (GP1balpha) expression, markers of megakaryocytic differentiation, was increased by staurosporine, but did not change significantly by NH2Cl and U0126. NH2Cl retarded cell proliferation without a marked loss of viability. When ERK phosphorylation (T202/Y204) and CD235 expression were compared using various chemicals, a strong negative correlation was observed (r = -0.76). Paradoxically, NH2Cl and staurosporine, but not U0126, induced large cells with multiple or lobulated nuclei, which was characteristic to megakaryocytes. NH2Cl increased the mRNA levels of gata1 and scl, decreased that of gata2, and did not change those of pu.1 and klf1. The changes observed in mRNA expression were different from those of U0126 or staurosporine. These results suggest that NH2Cl induces the bidirectional differentiation of K562. Oxidative stress may be effective in inducing leukemic cell differentiation. PMID- 24237254 TI - Specific IgG and IgA of common foods in Chinese children with eczema: friend or foe. AB - BACKGROUND: Specific immunoglobulins G and A (IgG and IgA) for common food items have been extensively measured as surrogate markers of food allergy, and dietary avoidance based on the test results advocated. AIM: We reviewed the prevalence of specific food IgG and IgA in children with eczema and evaluated outcome of dietary avoidance in these children. METHODS: Specific immunoglobulins of 96 food items were measured for 30 consecutive atopic dermatitis (AD) patients and disease severity [SCORing atopic dermatitis (SCORAD) and Nottingham eczema severity score (NESS)], Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL), topical corticosteroid and oral antihistamine usage were evaluated. Twenty seven of these patients received dietary avoidance advice based on IgG and IgA data. General acceptability of treatment (GAT) was documented at the end of 3 months. RESULTS: There were generally no correlations among levels of IgG or IgA of the 96 food items and disease severity, quality of life, SH or TEWL. Two-third patients reported very good or good and one-third reported fair or poor GAT following dietary avoidance advice. There was no difference in any clinical parameters between the two groups following dietary avoidance. Patient with lower sunflower seed IgA (p = 0.043), casein IgG (p = 0.041), milk IgG (p = 0.037) or whey IgG (p = 0.014) had improved SCORAD and objective SCORAD following dietary advice. CONCLUSION: Children with AD are sensitized to many food allergens via IgG and IgA mechanisms. Levels of food IgG or IgA do not seem to correlate with any clinical parameters in AD. Subjectively, two third of patients accepted dietary manipulations as very good or good for their AD. Objectively, dietary avoidance had few clinical effects on the clinical parameters. Sensitization should not be generalized to mean allergy to common food. PMID- 24237255 TI - Does a boar's season of birth determine semen parameters and reproductive performance? AB - This article studies the effect of a boar's birth season and breed on semen parameters and its further reproductive performance. Research material consisted of 72 boars from three breeds (24 Polish Large White PLW, 24 Polish Landrace PL, 24 Duroc * Pietrain D * P). During the whole period of the study, selected semen parameters were analysed: semen volume, spermatozoa concentration, total number of spermatozoa, total number of motile spermatozoa, number of insemination doses and also reproductive indicators: farrowing rate, total born litter size, total number of piglets born live and still, and average piglet weight. Boars born in the winter and summer months demonstrated the highest spermatozoa concentrations (383.25 and 392.37 * 10(6)/ml), total number of spermatozoa (91.75 and 93.21 * 10(9)), total number of motile spermatozoa (76.10 and 77.99 * 10(9)) and number of insemination doses (24.53 and 24.89; p <= 0.01). Statistically lower values for these parameters were observed for boars born in the spring and especially in autumn (p <= 0.01). The significant impact of birth season on farrowing rate (p <= 0.05) and average piglet weight (p <= 0.05) was confirmed for PLW boars. For the PL breed, only the total number of piglets born live was proven to be significantly affected (p <= 0.05). No impact of birth season was shown on semen quality or reproductive performance for D * P boars. In our study, we showed that the birth season of a boar had a more impact on the level of semen parameters, and less on the reproductive performance indicators. The results indicated that both the quality of semen and reproductive performance varied in terms of the study factors, as well as between individual breeds of boars involved in the experiment. PMID- 24237257 TI - Synthesis and reactivity of two-coordinate Ni(I) alkyl and aryl complexes. AB - Reaction of [(IPr)Ni(MU-Cl)]2 (1-Cl; IPr = 1,3-bis(2,6 diisopropylphenyl)imidazolin-2-ylidene) with ClMg{CH(SiMe3)2}.Et2O affords (IPr)Ni{CH(SiMe3)2} (2), a two-coordinate Ni(I) alkyl complex. An analogous two coordinate aryl derivative, (IPr)Ni(dmp) (dmp = 2,6-dimesitylphenyl), can be similarly prepared from Li(dmp) and 1-Cl. Reaction of 2 with alkyl bromides gives the three-coordinate Ni(II) alkyl halide complex (IPr)Ni{CH(SiMe3)2}Br. Evidence for a radical mechanism is presented to explain the reaction of 2 with alkyl halides. PMID- 24237258 TI - Delivering good service: personal resources, job satisfaction and nurses' 'customer' (patient) orientation. AB - AIMS: To explore the complex relationships between nurses' personal resources, job satisfaction and 'customer' (patient) orientation. BACKGROUND: Previous research has shown that nursing is highly intensive, emotionally charged work, which affects nurses' job performance and their customer orientation as well as patient or 'customer' satisfaction. This study contributes to the literature by examining how nurses' personal resources relate to their personal satisfaction and customer orientation and the relationships between them. Specifically, this study explores the effects of two facets of emotional labour (deep acting and surface acting), empathic concern, self-efficacy and emotional exhaustion on personal job satisfaction and customer orientation. We also test the moderating effects of inauthenticity and emotional contagion. DESIGN: A quantitative survey. METHOD: Data were collected through a self-completion questionnaire administered to a sample of 159 Australian nurses, in a public teaching hospital, in 2010. The data were analysed using Partial Least Square analysis. RESULTS: Partial Least Square analysis indicates that the final model is a good fit to the data (Goodness of Fit = 0.51). Deep acting and surface acting have different effects (positive and negative) on job satisfaction and 'customer' orientation, self efficacy has a positive effect on both and emotional exhaustion has a positive effect on customer orientation and a negative effect on job satisfaction. The moderating effects of emotional contagion and empathic concern, in the final model, are discussed. CONCLUSIONS: Understanding the complex interactions between personal resources, job satisfaction and customer orientation helps to increase service providers' (nurses in this study) personal satisfaction and 'customer' orientation particularly in difficult contexts. PMID- 24237260 TI - Adaptation of reproductive phenology to climate change with ecological feedback via dominance hierarchies. AB - Phenological shifts belong to the most commonly observed biological responses to recent climate change. It is, however, often unclear how these shifts are linked to demography and competitive interactions. We develop an eco-evolutionary model to study adaptation of timing of reproduction in organisms with social dominance hierarchies. We focus on residential birds with winter flocks, where success in competition for territories among offspring depends on ranking given by prior residence. We study the effects of environmental change on breeding population densities, ensuing selection pressures and long-term evolutionary equilibria. We consider changes in food peak date, in winter survival, in total reproductive output and in the width of the food distribution. We show that the evolutionarily stable hatching date will advance with increasing winter survival and reproductive output since these parameters increase habitat saturation and post fledging competition. Increasing the length of the breeding season also selects for earlier hatching date due to the reduced costs for producing offspring with high ranking. Our analysis shows that there is little correlation between short term and long-term population responses across different scenarios of environmental change. However, short-term population growth consistently predicts selection for earlier reproduction. Hence, the model identifies changed breeding population density as a key factor to understanding phenological adaptation in systems with prior residence advantages. While selection for change in reproductive phenology is often explained by changed seasonal variation in environmental variables, such as food abundance, we show that environmental change without apparent effects on seasonality can critically affect phenological adaptation. Such factors can mask or even override influences of changed seasonality on phenology. The model thus offers a conceptually new set of explanations for understanding phenological and demographic trends in a changing climate. PMID- 24237261 TI - Mercator: a fast and simple web server for genome scale functional annotation of plant sequence data. AB - Next-generation technologies generate an overwhelming amount of gene sequence data. Efficient annotation tools are required to make these data amenable to functional genomics analyses. The Mercator pipeline automatically assigns functional terms to protein or nucleotide sequences. It uses the MapMan 'BIN' ontology, which is tailored for functional annotation of plant 'omics' data. The classification procedure performs parallel sequence searches against reference databases, compiles the results and computes the most likely MapMan BINs for each query. In the current version, the pipeline relies on manually curated reference classifications originating from the three reference organisms (Arabidopsis, Chlamydomonas, rice), various other plant species that have a reviewed SwissProt annotation, and more than 2000 protein domain and family profiles at InterPro, CDD and KOG. Functional annotations predicted by Mercator achieve accuracies above 90% when benchmarked against manual annotation. In addition to mapping files for direct use in the visualization software MapMan, Mercator provides graphical overview charts, detailed annotation information in a convenient web browser interface and a MapMan-to-GO translation table to export results as GO terms. Mercator is available free of charge via http://mapman.gabipd.org/web/guest/app/Mercator. PMID- 24237262 TI - Cellular level classification of breast cancer through proteomic markers using nanochannel array sensors. AB - Aims: A nanochannel-based sensor for cellular level classification of breast cancer metastasis has been designed. Our approach to the classification of cell's likelihood to metastasize is based on screening for levels of expression of specific proteomic biomarkers associated with breast cancer stem cells. Materials & methods: Proteomic activity for four breast cancer cell lines for three specific markers (PDGFR, ALDH1A1 and ALDH1A3) was quantified. The nanochannel sensor is an electrochemical immunoassay and comprises of alumina nanochannel arrays integrated on to a gold microelectronic platform. The sensor operates on the principle of electrochemical impedance spectroscopy. Results & conclusion: Test cell lysate samples from SUM159 invasive, SUM159 noninvasive, HC1143 and DCIS cell lines were classified as those having a high likelihood of metastases based on the levels of proteomic activity evaluated against the three key markers. The lowest proteomic activity measured was 0.1 ng/ml with PDGFR, 100 ng/ml with ALDH1A1 and 100 ng/ml with ALDH1A3, correlating to the detection of unit stem cell count. Original submitted 9 November 2012; Revised submitted 29 July 2013. PMID- 24237264 TI - Zigzag inversion domain boundaries in indium zinc oxide-based nanowires: structure and formation. AB - Existing models for the crystal structure of indium zinc oxide (IZO) and indium iron zinc oxide (IFZO) conflict with electron microscopy data. We propose a model based on imaging and spectroscopy of IZO and IFZO nanowires and verify it using density functional theory. The model features a {121 [symbol: see text]} "zigzag" layer, which is an inversion domain boundary containing 5-coordinate indium and/or iron atoms. Higher [symbol: see text] values are observed for greater proportion of iron. We suggest a mechanism of formation in which the basal inclusion and the zigzag diffuse inward together from the surface of the nanowire. PMID- 24237265 TI - Hair cycle control by leptin as a new anagen inducer. AB - Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5-week-old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5-week-old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild-type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22-56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild-type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild-type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT-PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well-known adipokine, acts as an anagen inducer and represents a new player in hair biology. PMID- 24237263 TI - Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins. AB - AIMS: Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson's disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle ('nanozyme') with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices. METHODS: Synthesis, characterization and therapeutic efficacy of optimal cell-based nanoformulations are evaluated. RESULTS: A formulation design for drug carriers typically works to avoid entrapment in monocytes and macrophages focusing on small-sized nanoparticles with a polyethylene glycol corona (to provide a stealth effect). By contrast, the best nanozymes for delivery in macrophages reported in this study have a relatively large size (~ 200 nm), which resulted in improved loading capacity and release from macrophages. Furthermore, the cross-linking of nanozymes with the excess of a nonbiodegradable linker ensured their low cytotoxicity, and efficient catalase protection in cell carriers. Finally, the 'alternatively activated' macrophage phenotype (M2) utilized in these studies did not promote further inflammation in the brain, resulting in a subtle but statistically significant effect on neuronal regeneration and repair in vivo. CONCLUSION: The optimized cross-linked nanozyme loaded into macrophages reduced neuroinflammatory responses and increased neuronal survival in mice. Importantly, the approach for nanoformulation design for cell-mediated delivery is different from the common requirements for injectable formulations. PMID- 24237266 TI - Rationally designed nucleobase and nucleotide coordinated nanoparticles for selective DNA adsorption and detection. AB - Nanomaterials for DNA adsorption are useful for sequence-specific DNA detection. Current materials for DNA adsorption employ electrostatic attraction, hydrophobic interaction, or pi-pi stacking, none of which can achieve sequence specificity. Specificity might be improved by involving hydrogen bonding and metal coordination. In this work, a diverse range of nucleobase/nucleotide (adenine, adenosine, adenosine 5'-triphosphate (ATP), adenosine 5'-monophosphate (AMP), and guanosine 5'-triphosphate (GTP)) coordinated materials containing various metal ions (Au(III), Ag(I), Ce(III), Gd(III), and Tb(III)) are prepared. In most cases, nanoparticles are formed. These materials have different surface charges, and positively charged particles only show nonspecific DNA adsorption. Negatively charged materials give different adsorption kinetics for different DNA sequences, where complementary DNA homopolymers are adsorbed faster than other sequences. Therefore, the bases in the coordinated materials can still form base pairs with the DNA. The adsorption strength is mainly controlled by the metal ions, where Au shows the strongest adsorption while lanthanides are weaker. These materials can be used as sensors for DNA detection and can also deliver DNA into cells with no detectable toxicity. By tuning the nanoparticle formulation, enhanced detection can be achieved. This study is an important step toward rational design of materials to achieve specific interactions between biomolecules and synthetic nanoparticle surfaces. PMID- 24237267 TI - A novel safety assessment strategy for non-intentionally added substances (NIAS) in carton food contact materials. AB - One of the main challenges in food contact materials research is to prove that the presence of non-intentionally added substances (NIAS) is not a safety issue. Migration extracts may contain many unknown substances present at low concentrations. It is difficult and time-consuming to identify all these potential NIAS and concurrently to assess their health risk upon exposure, whereas the health relevance at low exposure levels might not even be an issue. This paper describes a scientifically based, but pragmatic safety assessment approach for unknown substances present at low exposure levels in food contact matrices. This complex mixture safety assessment strategy (CoMSAS) enables one to distinguish toxicologically relevant from toxicologically less relevant substances, when related to their respective levels of exposure, and allows one to focus on the substances of potential health concern. In particular, substances for which exposure will be below certain thresholds may be considered not of health relevance in case specific classes of substances are excluded. This can reduce the amount of work needed for identification, characterisation and evaluation of unknown substances at low concentration. The CoMSAS approach is presented in this paper using a safety assessment of unknown NIAS that may migrate from three carton samples. PMID- 24237268 TI - Thermochemical factors affecting the dehalogenation of aromatics. AB - Halogenated aromatics are one of the largest chemical classes of environmental contaminants, and dehalogenation remains one of the most important processes by which these compounds are degraded and detoxified. The thermodynamic constraints of aromatic dehalogenation reactions are thus important for understanding the feasibility of such reactions and the redox conditions necessary for promoting them. Accordingly, the thermochemical properties of the (poly)fluoro-, (poly)chloro-, and (poly)bromobenzenes, including standard enthalpies of formation, bond dissociation enthalpies, free energies of reaction, and the redox potentials of Ar-X/Ar-H couples, were investigated using a validated density functional protocol combined with continuum solvation calculations when appropriate. The results highlight the fact that fluorinated aromatics stand distinct from their chloro- and bromo- counterparts in terms of both their relative thermodynamic stability toward dehalogenation and how different substitution patterns give rise to relevant properties, such as bond strengths and reduction potentials. PMID- 24237269 TI - Antifungal activity of biogenic tellurium nanoparticles against Candida albicans and its effects on squalene monooxygenase gene expression. AB - In this study, we evaluated the antifungal activity of biogenic tellurium nanoparticles (Te NPs) against Candida albicans (ATCC14053). In addition, the effect of these biogenic NPs on squalene monooxygenase activity and the squalene monooxygenase gene (ERG1) expression level was evaluated. Squalene monooxygenase is an important enzyme involved in the synthesis of ergosterol, cholesterol, and phytosterols. Because of the importance of the noted compound, the squalene monooxygenase gene could be considered a good antifungal target. Results showed that biogenic Te NPs had antifungal effect against C. albicans. The minimal fungicidal concentration-minimal inhibitory concentration ratios of the biogenic Te NPs revealed that these NPs exhibited fungicidal effects against the test strain. The results of an enzyme assay using quantitative high-performance liquid chromatography showed squalene accumulation in C. albicans cells because of enzyme inhibition. Real-time PCR analysis showed an increase in the expression of the ERG1 gene in C. albicans cells, which were treated with Te NPs (0.2 mg/mL). It is conclution that Te NPs can inhibit the squalene monooxygenase enzyme, and, as a result, this inhibition phenomenon can cause an increase in the expression level of the ERG1 gene. This is the first report of the anti-Candida effect of biogenic Te NPs and its possible mechanisms. PMID- 24237270 TI - Development of fine motor skills in preterm infants. AB - Fine motor skills are related to functioning in daily life and at school. We reviewed the status of knowledge, in preterm children, on the development of fine motor skills, the relation with gross motor skills, and risk factors for impaired fine motor skills. We searched the past 15 years in PubMed, using ['motor skills' or 'fine motor function' and 'preterm infant'] as the search string. Impaired gross and fine motor skills are among the most frequently occurring problems encountered by preterm children who do not develop cerebral palsy. The prevalence is around 40% for mild to moderate impairment and 20% for moderate impairment. Fine motor skill scores on the Movement Assessment Battery for Children are about 0.62 of a standard deviation lower compared with term children. Risk factors for fine motor impairments include moderately preterm birth (odds ratio [OR] 2.0) and, among very preterm children (<32 wk gestation), intra-uterine growth restriction (ORs 2-3), inflammatory conditions (late-onset sepsis and necrotizing enterocolitis, ORs 3-5), and dexamethasone therapy for bronchopulmonary dysplasia (OR 2.7). A better understanding of factors that play a role in the development of and recovery from brain injury could guide future intervention attempts aimed at improving fine motor skills of preterm children. PMID- 24237271 TI - Typical and atypical development of reaching and postural control in infancy. AB - Successful reaching requires postural control, either by active regulation or by postural support. The present paper reviews literature on typical and atypical development of reaching and postural control during infancy. Typically, reaching movements end in grasping around 4 months of age. Initially, reaches are characterized by large variation, including many trajectory corrections. During the first year, the movements get increasingly straight and smooth. Reaching in low-risk preterm infants is initially characterized by advanced development, but minor impairments may emerge in the second half of infancy. In high-risk preterm infants, development of reaching is characterized by delay and non-optimal reaching performance. Typical development of postural adjustments is characterized by variation and an increasing ability to adapt the variable repertoire to the specifics of the situation. The latter is facilitated by an increasing role of anticipatory mechanisms in the second half of infancy. Atypically developing infants may have a reduced repertoire and usually have difficulties in adapting postural adjustments. In infancy, most reaching movements are performed during sitting. The postural challenge of sitting may interfere in particular with the development of reaching in atypically developing infants. The practical implications of this suggestion are discussed. PMID- 24237272 TI - Separate visual systems for perception and action: a framework for understanding cortical visual impairment. AB - The visual control of skilled goal-directed movements requires transformations of incoming visual information that are quite different from those required for visual perception. These differences in the required computations have led to the emergence of dedicated visuomotor modules in the dorsal visual stream of the cerebral cortex that are quite separate from the networks in the ventral visual stream that mediate our conscious perception of the world. Although the identification and selection of goal objects and an appropriate course of action depends on the perceptual machinery of the ventral stream and associated cognitive modules in the temporal and frontal lobes, the execution of the subsequent goal-directed action is mediated by dedicated online control systems in the dorsal stream and associated motor areas. This functional distinction can provide a useful framework for interpreting the range of perceptual and visuomotor deficits observed in children with cortical visual impairment. PMID- 24237273 TI - Visual control of manual actions: brain mechanisms in typical development and developmental disorders. AB - Some key stages in the development of manual actions have been discussed in this supplement based on the idea of the dorsal cortical stream as the pathway for translating visual information into action control. We argue that visual information, transmitted through specialized visuomotor dorsal-stream modules, is required in the control of manual actions for selecting and attending to the target object of the action, translating visual spatial information into motor programmes and planning a coordinated sequence of actions so as to reach an optimal end-state. In typical development, we illustrate dorsal-stream processing through results on the use of stereoscopic information to guide infants' reaches, and changes in target selection and detailed kinematics of reaches depending on age, object size, and reaching in darkness (when dorsal-stream information rapidly decays). We hypothesize 'dorsal-stream vulnerability' as a widespread feature of neurodevelopmental disorders, such as autism, Williams syndrome, and children born very preterm. Such deficits, identified as abnormal visuomanual actions, are seen in bimanual coordination, visual guidance of action in the 'postbox' task, and failures in motor planning for end-state comfort. We discuss the possible application of these approaches to a wider range of disorders including developmental coordination disorder. PMID- 24237274 TI - Visuospatial and visuomotor deficits in preterm children: the involvement of cerebellar dysfunctioning. AB - One of the more consistent findings in follow-up studies of preterm children is a deficit in visuospatial and visuomotor skills. Impairment of the dorsal visual stream and basal ganglia damage have been hypothesized to underlie this deficit. However, given recent findings of impaired cerebellar development in preterm children without lesions to this structure, and the involvement of the cerebellum in visuospatial and visuomotor functioning, we argue the cerebellum should be included in models relating impaired development of brain networks to visuospatial and visuomotor deficits in this population. Here, we review the current literature on impaired cerebellar development in preterm children, and suggest possible underlying mechanisms. PMID- 24237275 TI - Reorganization of visual fields after periventricular haemorrhagic infarction: potentials and limitations. AB - Visual functions are often impaired in preterm infants with periventricular haemorrhagic infarction, because of the involvement of the region where the optic radiations are located. In some cases an unexpected sparing of the visual fields has been described, and related to the plasticity of thalamo-cortical afferents that are supposedly able to bypass the lesion when it occurs in the early third trimester of gestation. We systematically reviewed the literature in the field to determine the limits and potentials of this type of reorganization. We found four studies meeting our criteria, from which we extracted case reports on 19 individuals with intraventricular haemorrhagic infarction. Eleven of the 19 did not have visual field defects, five had a bilateral visual field defect, and the remaining three had a unilateral visual field defect. The involvement of the optic radiations was often associated with normal visual fields as only one of the four individuals with damaged optic radiations showed visual field defects. Conversely, the presence of basal ganglia/thalamus involvement apparently prevented such reorganization, as the only two individuals with unilateral field restriction and available magnetic resonance imaging data both showed abnormalities in those structures. Consistent with this, we report on a further individual in which visual field restriction was associated with abnormal tractography on brain magnetic resonance imaging. Overall, this review supports the existence of effective mechanisms of plastic reorganization that allow a rewiring of geniculo-calcarine connections with restoration of full field vision but which are hindered by the involvement of the basal ganglia and thalamus. PMID- 24237276 TI - Pathophysiological mechanisms of impaired limb use and repair strategies for motor systems after unilateral injury of the developing brain. AB - The corticospinal tract (CST) is important for limb control. In humans, it begins developing prenatally but CST connections do not have a mature pattern until about 6 months of age and its capacity to evoke muscle contraction does not mature until mid-adolescence. An initially bilateral projection is subsequently refined, so that most ipsilateral CST connections are eliminated. Unilateral brain damage during refinement leads to bilateral developmental impairments. The damaged side develops sparse and weak contralateral spinal connections and the non-involved hemisphere maintains its ipsilateral projection to develop an aberrant bilateral spinal projection. In a kitten model of unilateral spastic cerebral palsy, we replicate key features of the CST circuit changes: robust bilateral CST projections from the non-involved hemisphere, sparse contralateral connections from the affected hemisphere, and motor impairments. We discuss the role of activity-dependent synaptic competition in development of bilateral CSTs and consider several experimental strategies for restoring a more normal pattern of CST connections from the damaged and non-involved sides. We highlight recent results stressing the importance of combined repair of CST axons, restoration of a more normal motor cortex motor representation, and key involvement of spinal cholinergic interneurons in restoring skilled motor function. PMID- 24237277 TI - Pathophysiology of impaired hand function in children with unilateral cerebral palsy. AB - Unilateral spastic cerebral palsy, caused by damage to the developing central nervous system, is characterized by motor impairments mainly lateralized to one side of the body, with hand impairments greatly contributing to functional limitations. The integrity of the motor areas and the corticospinal tract (CST) is often compromised. The specific etiology may drastically influence subsequent development of CST pathways. Here we describe the pathophysiology underlying impaired upper extremity function, with particular emphasis on the relation between CST damage and hand function. We also describe the resulting sensory and motor deficits, with an emphasis on studies of precision grip, which highlight impairments in motor execution, sensorimotor integration, motor planning, and bimanual coordination beyond dexterity impairments. We show that the type and extent of early brain damage and/or CST reorganization is highly predictive of the severity of these impairments. We discuss the clinical implications of these findings, including the intriguing possibility that the specific pathophysiology is predictive of treatment outcomes. We suggest that a 'one-treatment fits all approach' may be insufficient, and that future rehabilitation efforts will be best guided by closely relating treatment efficacy with the specific pathophysiology. PMID- 24237278 TI - Upper limb activity in children with unilateral spastic cerebral palsy: the role of vision in movement strategies. AB - This article reviews the capacity of children with unilateral spastic cerebral palsy (USCP) to (re)organize the available degrees of freedom and to use visual information in interceptive actions during motion with either the impaired or the less-impaired hand. Atypical reaching movements, such as increased trunk movement or slower wrist velocity, are considered adaptive coordination patterns that are the result of a change in the constraints. It is argued that manipulation of the task context facilitates children with USCP to enhance performance. For example, when reducing the time available to intercept a ball, the children are found to exceed their usual maximum walking speed and to increase range of motion of the elbow. In addition, the children appear to rely on a visual information strategy similar to typically developing children ('bearing angle'), although more variability is observed when using the impaired arm. The implications for interventions are, it should be recognized, that these children adapt to the impairment by reorganizing the movement system and that this process can be influenced by changing the task context. Attention should be paid to the importance of using correct visual cues for initiation and guidance of interceptive actions, which may be provoked by using external visual triggers. PMID- 24237279 TI - Impaired motor planning and motor imagery in children with unilateral spastic cerebral palsy: challenges for the future of pediatric rehabilitation. AB - Compromised action performance is one of the most characteristic features of children with unilateral spastic cerebral palsy (USCP). Current rehabilitation efforts predominantly aim to improve the capacity and performance of the affected arm. Recent evidence, however, suggests that compromised motor planning may also negatively affect performance of activities of daily living. In this paper we will first discuss the recent evidence for this motor planning deficit, followed by studies on motor imagery in this population. Motor imagery is an experimental approach in which the contents of the motor plan become overt. Converging evidence indicates a compromised motor imagery ability in USCP. As the neural structures of both motor planning and motor imagery overlap, rehabilitation by motor imagery training may alleviate motor problems in USCP. Increasing evidence for this approach exists in older adults with stroke. We conclude this review with recommendations on such a training approach for children with USCP. PMID- 24237280 TI - Does goal setting in activity-focused interventions for children with cerebral palsy influence treatment outcome? AB - Today, treatment for children with cerebral palsy predominantly aims at improving the children's possibilities to perform everyday activities in their natural environment. The activities in focus for intervention are often expressed as specific goals, frequently defined in a collaborative goal-setting process between professionals and parents. The role of goal setting to improve the outcome of the intervention has not been shown in the literature so far. Thus, the aim of this systematic review was to explore if goal setting has an impact on treatment outcome assessed by standardized measures. CINAHL and MEDLINE were searched from January 2000 to October 2012, resulting in a final selection of 13 articles, six of which were randomized controlled trials. Methodological quality was assessed and study characteristics were analysed descriptively. Subject characteristics, type of intervention/s, frequency, and intensity of therapy varied largely. Outcome was assessed by standardized outcome measures as well as evaluated through aspects of goal attainment. Most studies showed robust within group changes according to study-appropriate standardized measures, whereas the between-group comparisons exhibited less consistent differences in outcome. The review does not provide support for a positive effect of goal setting per se on treatment outcome. Studies that specifically measure the effect of goal setting on treatment outcome are needed. PMID- 24237281 TI - Is developmental coordination disorder a fundamental cause of inactivity and poor health-related fitness in children? AB - Developmental coordination disorder (DCD) is a common, neurodevelopmental disorder of children that results in significant impairment in everyday activities of living. Over the past two decades, a large body of work has documented associations between DCD, physical inactivity, and poor health-related fitness. The exact nature of these relations, however, has been relatively little studied. In this paper, we ask whether the balance of evidence supports the proposition that DCD is a fundamental cause of inactivity and poor fitness. To address this question, we apply Hill's criteria for causation. We conclude that the evidence is consistent with, and reasonably supportive of, this proposition, but does not exclude alternative explanations. PMID- 24237282 TI - Neural correlates of developmental coordination disorder. AB - AIM: To review neuroimaging studies in children with developmental coordination disorder (DCD) systematically. Because only a few studies addressed this, we broadened our search and included neuroimaging studies in children with perinatal adversities and motor impairment without cerebral palsy. METHOD: Two searches were performed in PubMed, PsycINFO, and Web of Science addressing (1) neuroimaging in DCD and (2) neuroimaging in children with perinatal adversities and motor impairment. RESULTS: Five studies in children with DCD were identified. Four functional magnetic resonance imaging (MRI) studies showed that children with DCD activate multiple brain areas differently than controls. One diffusion tensor imaging study indicated that the internal capsule in children with DCD showed differences. The second search identified seven studies: three showed that white matter abnormalities and severe abnormalities on MRI were related to motor impairment; four were unable to demonstrate similar relationships. INTERPRETATION: Data on neuroimaging in DCD are scarce; data available suggest that multiple brain areas are involved in the neuropathophysiology of DCD. Motor impairment in children with perinatal adversities is related especially to white matter abnormalities and severe abnormalities on MRI. We hypothesize that in some children with DCD the neural substrate mimics that of cerebral palsy. More neuroimaging studies are needed to understand the neural correlates of DCD better. PMID- 24237283 TI - Neural correlates of paediatric dysgraphia. AB - Writing is an important skill that is related both to school performance and to psychosocial outcomes such as the child's self-esteem. Deficits in handwriting performance are frequently encountered in children with developmental coordination disorder. This review focuses on what is known about the neural correlates of atypical handwriting in children. Knowledge of the neural correlates is derived from studies using clinical case designs (e.g. lesion studies), studies using neuroimaging, and assessment of minor neurological dysfunction. The two functional imaging studies suggest a contribution of cortical areas and the cerebellum. The largest study indicated that cortical areas in all regions of the brain are involved (frontal, temporal, parietal, and occipital). The two lesion studies confirmed cerebellar involvement. The findings of the study on minor neurological dysfunction in children with writing problems correspond to the imaging results. The limited data on the neural substrate of paediatric dysgraphia suggest that at least a subset of the children with dysgraphia have dysfunctions in extensive supraspinal networks. In others, dysfunction may be restricted to either the cerebellum or specific cortical sites. PMID- 24237284 TI - Noise, variability, and motor performance in developmental coordination disorder. AB - Variability and noise are a natural part of the neuromuscular system, and can occur at multiple levels. However, excessive neural noise in the motor system makes the problem of control much harder. Disruption of basic sensory inputs will exacerbate the problem, impacting one's sense of position in space (or body schema) and the ability of the motor system to predict its own dynamics. So called predictive control is fundamental to movement efficiency and accuracy, but has been shown to be poorly developed in children with motor problems like developmental coordination disorder. These children manifest a core deficit in predictive control, which is expressed by high levels of variability across tasks, and at the level of movement kinematics, for example patterns of inter limb coordination. As such, they rely heavily on feedback mechanisms to exert control, the outcome being slower and more laboured movements, and reduced responsiveness to changes in the environment. We discuss these issues of high variability and noise in developmental coordination disorder in relation to motor prediction, and with an eye to remediation. Issues of task scheduling and use of augmented feedback are important considerations for therapists when treating these children. PMID- 24237285 TI - Mastery of manual skills: recent insights into typical and atypical development of manual ability. PMID- 24237286 TI - CuI-catalyzed C1-alkynylation of tetrahydroisoquinolines (THIQs) by A3 reaction with tunable iminium ions. AB - A CuI-catalyzed A(3) (amines, aldehydes and alkynes) reaction of tetrahydroisoquinolines (THIQs), aldehydes, and alkynes to give C1-alkynylated THIQ products (endo-yne-THIQs) was developed. This redox neutral C1-alkynylation of THIQs, which was conducted under mild conditions, has a broad scope for the used aldehydes and alkynes. It was proposed that the A(3) reaction first generates in situ exo-iminium ions, which then isomerize to endo-iminium ions and react with copper acetylides to give the endo alkynylated THIQs (endo-yne-THIQs). PMID- 24237287 TI - The quality of mental health information commonly searched for on the Internet. AB - Previous research has reviewed the quality of online information related to specific mental disorders. Yet, no comprehensive study has been conducted on the overall quality of mental health information searched for online. This study examined the first 20 search results of two popular search engines-Google and Bing-for 11 common mental health terms. They were analyzed using the DISCERN instrument, an adaptation of the Depression Website Content Checklist (ADWCC), Flesch Reading Ease and Flesch-Kincaid Grade Level readability measures, HONCode badge display, and commercial status, resulting in an analysis of 440 web pages. Quality of Web site results varied based on type of disorder examined, with higher quality Web sites found for schizophrenia, bipolar disorder, and dysthymia, and lower quality ratings for phobia, anxiety, and panic disorder Web sites. Of the total Web sites analyzed, 67.5% had good or better quality content. Nearly one-third of the search results produced Web sites from three entities: WebMD, Wikipedia, and the Mayo Clinic. The mean Flesch Reading Ease score was 41.21, and the mean Flesch-Kincaid Grade Level score was 11.68. The presence of the HONCode badge and noncommercial status was found to have a small correlation with Web site quality, and Web sites displaying the HONCode badge and commercial sites had lower readability scores. Popular search engines appear to offer generally reliable results pointing to mostly good or better quality mental health Web sites. However, additional work is needed to make these sites more readable. PMID- 24237288 TI - Facebook photo activity associated with body image disturbance in adolescent girls. AB - The present study examined the relationship between body image and adolescent girls' activity on the social networking site (SNS) Facebook (FB). Research has shown that elevated Internet "appearance exposure" is positively correlated with increased body image disturbance among adolescent girls, and there is a particularly strong association with FB use. The present study sought to replicate and extend upon these findings by identifying the specific FB features that correlate with body image disturbance in adolescent girls. A total of 103 middle and high school females completed questionnaire measures of total FB use, specific FB feature use, weight dissatisfaction, drive for thinness, thin ideal internalization, appearance comparison, and self-objectification. An appearance exposure score was calculated based on subjects' use of FB photo applications relative to total FB use. Elevated appearance exposure, but not overall FB usage, was significantly correlated with weight dissatisfaction, drive for thinness, thin ideal internalization, and self-objectification. Implications for eating disorder prevention programs and best practices in researching SNSs are discussed. PMID- 24237289 TI - Artefactual responses of mesophyll conductance to CO2 and irradiance estimated with the variable J and online isotope discrimination methods. AB - Studies with the variable J method have reported that mesophyll conductance (gm ) rapidly decreases with increasing intercellular CO2 partial pressures (Ci ) or decreasing irradiance. Similar responses have been suggested with the online isotope discrimination method, although with less consistency. Here we show that even when the true gm is constant, the variable J method can produce an artefactual dependence of gm on Ci or irradiance similar to those reported in previous studies for any of the following factors: day respiration and chloroplastic CO2 photocompensation point are estimated with Laisk method; Ci or electron transport rate is positively biased; net photosynthetic rate is negatively biased; insufficient NADPH is assumed while insufficient ATP limits RuBP regeneration. The isotopic method produces similar artefacts if fractionation of carboxylation or Ci is positively biased or Delta(13) negatively biased. A non-zero chloroplastic resistance to CO2 movement results in a qualitatively different dependence of gm on Ci or irradiance and this dependence is only sensitive at low Ci . We thus cannot rule out the possibility that previously reported dependence of gm on Ci or irradiance is a methodological artefact. Recommendations are made to take advantage of sensitivities of the variable J and isotopic methods for estimating gm . PMID- 24237290 TI - Welcome to the Journal of Comparative Effectiveness Research. AB - As the Senior Editors of the Journal of Comparative Effectiveness Research (JCER) we are delighted to present you with the first issue of this exciting new publication, focusing on the socially and clinically impactful field of comparative effectiveness research (CER). PMID- 24237293 TI - From methods to policy: the intended and unintended consequences of comparative effectiveness research. PMID- 24237291 TI - Comparing treatments for idiopathic sudden sensorineural hearing loss. PMID- 24237294 TI - AcademyHealth and the future of comparative effectiveness research: making sure evidence matters. AB - Dr Lisa Simpson is the president and CEO of AcademyHealth, and its advocacy arm, the Coalition for Health Services Research. A nationally recognized health policy researcher and pediatrician, Dr Simpson is a passionate advocate for the translation of research into policy and practice. Before joining AcademyHealth, Dr Simpson was director of the Child Policy Research Center at Cincinnati Children's Hospital Medical Center and Professor of Pediatrics in the Division of Health Policy and Clinical Effectiveness, Department of Pediatrics, University of Cincinnati (OH, USA). She served as the Deputy Director of the Agency for Healthcare Research and Quality (AHRQ) from 1996 to 2002. She previously served on the Institute of Medicine's Committee on Comparative Effectiveness Research Priorities and the Committee on Highly Effective Clinical Services. Dr Simpson is a member of the Robert Wood Johnson Clinical Scholars Program National Advisory Council and the AHRQ Healthcare Cost and Utilization Project (HCUP) Steering Committee. Dr Simpson's research focuses on improving the performance of the healthcare system and includes studies of the quality and safety of care, the role of health information technology in improving the quality of care, health and healthcare disparities, and the health policy and system response to childhood obesity. Dr Simpson earned her undergraduate and medical degrees at Trinity College (Dublin, Ireland), a master's in public health at the University of Hawaii (HI, USA), and completed a post-doctoral fellowship in health services research and health policy at the University of California, San Francisco (CA, USA). PMID- 24237295 TI - Comparative effectiveness research and measuring the level of pharmaceutical innovation in the EU. AB - Over the past 50 years, medicines have made a huge contribution to improving the health status of populations. However, the level of pharmaceutical innovation varies widely, ranging from breakthrough treatments for life-threatening diseases to minor modifications of medicines that have been on the market for some time. Once innovative medicines approach the market, a system of measuring the level of innovation should be established. This perspective describes the current situation, the challenges and initiatives, and formulates recommendations for a coordinated EU action to measure the level of pharmaceutical innovation. In our opinion, comparative effectiveness research needs to play a central role in measuring the level of pharmaceutical innovation. PMID- 24237296 TI - Clinical practice change requires more than comparative effectiveness evidence: abdominal aortic aneurysm management in the USA. AB - Adoption of healthcare innovations frequently outpaces the evidence of effectiveness. Endovascular repair (EVAR) for abdominal aortic aneurysms in the USA demonstrates how comparative effectiveness research without evidence-based reimbursement changes may fail to influence clinical practice. Randomized controlled trials for small abdominal aortic aneurysms demonstrate no lasting benefits of EVAR or open surgical repair (OSR) compared with surveillance, and for large abdominal aortic aneurysms demonstrate no lasting survival benefit of EVAR over OSR, and do show poorer durability and higher costs for EVAR. Nonetheless, >50% of elective abdominal aortic aneurysm repairs in the USA use EVAR. Factors that may be driving the high use of EVAR include patient preference, surgeons' desire to appear 'up-to-date' in the procedures they offer, higher hourly surgeon reimbursement for EVAR than OSR, and the expansion of physician specialties able to perform abdominal aortic aneurysm repair from only vascular surgeons with OSR, to vascular surgeons and interventional radiologists/cardiologists with EVAR. By comparison, in Canada, where government health insurance restricts EVAR coverage to high surgical risk patients, only approximately 25% of abdominal aortic aneurysm repairs are performed using EVAR. Country-specific cost studies and a prospective population-based study collecting detailed clinical data to identify patient subgroups that truly benefit from a particular management strategy are needed to inform policy regarding EVAR availability and reimbursement. PMID- 24237297 TI - Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? AB - High-dose chemotherapy and autologous stem cell transplantation remains a standard procedure in relatively young and selected older patients with multiple myeloma. High-dose melphalan has remained the chemotherapeutic agent of choice based on earlier prospective randomized trials. Despite investigations involving different combinations of chemotherapeutics, radiation and novel agents with and without melphalan, none of these alternative preparative regimens have demonstrated superiority to high-dose melphalan used as a single agent in multiple published studies. In this article, we review the published literature regarding preparative regimens used in patients with multiple myeloma undergoing autologous stem cell transplantation. PMID- 24237298 TI - Comparative effectiveness research in obstructive sleep apnea: bridging gaps between efficacy studies and clinical practice. AB - Comparative effectiveness research encompasses research that compares two interventions to each other, and takes place in real-world settings without strict inclusion and exclusion criteria, according to the established standard of care. There is a need for comparative evaluations of the treatments for obstructive sleep apnea, a disease associated with increased cardiovascular risk, stroke and metabolic derangement. This article reviews the recent, representative literature that addresses obstructive sleep apnea intervention and treatment, paradigms for diagnosis and randomized control trials addressing the efficacy of interventions, in an effort to demonstrate examples of both traditional observational and randomized control trials, as well as to illustrate the considerable overlap between some traditional studies and comparative effectiveness research. Despite methodological challenges, the potentially large clinical and public health impact of obstructive sleep apnea, accompanied by considerable cost, mandates that randomized controlled trials and comparative effectiveness research be systematically applied to identify both the efficacy and effectiveness of alternative diagnosis and treatment strategies. PMID- 24237300 TI - A double-blind randomized controlled study to evaluate the efficacy of low-dose oral interferon-alpha in preventing hepatitis C relapse. AB - Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4-1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy. PMID- 24237301 TI - Interferon-gamma-induced intestinal epithelial barrier dysfunction by NF kappaB/HIF-1alpha pathway. AB - Interferon-gamma (IFN-gamma) plays an important role in intestinal barrier dysfunction. However, the mechanisms are not fully understood. As hypoxia inducible factor-1 (HIF-1) is a critical determinant response to hypoxia and inflammation, which has been shown to be deleterious to intestinal barrier function, we hypothesized that IFN-gamma induces loss of barrier function through the regulation of HIF-1alpha activation and function. In this study, we detected the expressions of HIF-1alpha and tight junction proteins in IFN-gamma-treated T84 intestinal epithelial cell line. IFN-gamma led to an increase of HIF-1alpha expression in time- and dose-dependent manners but did not change the expression of HIF-1beta. The IFN-gamma-induced increase in HIF-1alpha was associated with an activation of NF-kappaB. Treatment with the NF-kappaB inhibitor, pyrolidinedithiocarbamate (PDTC), significantly suppressed the activation of NF kappaB and the expression of HIF-1alpha. In addition, IFN-gamma also increased intestinal epithelial permeability and depletion of tight junction proteins; inhibition of NF-kappaB or HIF-1alpha prevented the increase in intestinal permeability and alteration in tight junction protein expressions. Interestingly, we demonstrated that a significant portion of IFN-gamma activation NF-kB and modulation tight junction expression is mediated through HIF-1alpha. Taken together, this study suggested that IFN-gamma induced the loss of epithelial barrier function and disruption of tight junction proteins, by upregulation of HIF-1alpha expression through NF-kappaB pathway. PMID- 24237302 TI - Gonadal status and outcome of bariatric surgery in obese men. AB - BACKGROUND: Obesity-related hypogonadotrophic hypogonadism (OrHH) occurs in over 40% of morbidly obese men. Obesity-related hypogonadotrophic hypogonadism may reduce the beneficial effects of bariatric surgery. OBJECTIVE: To assess the impact of OrHH on the outcome of bariatric surgery in men. PATIENTS AND METHODS: Observational study with measurement of serum gonadal hormones, and assessment of body composition, glucose, lipid and bone metabolism during the first year after bariatric surgery in 13 men with OrHH (free testosterone (free T) <225 pmol/l) and 11 age-matched eugonadal morbidly obese men (free T > 225 pmol/l). RESULTS: Serum free T was inversely related to body weight (R = -0.65, P < 0.0001) and rose gradually after bariatric surgery, in eugonadal as well as in OrHH men, by 30 pmol/l for every 10 kg loss of weight. In three patients, serum free T remained within the hypogonadal range despite substantial weight loss. Gonadal hormone status prior to surgery did not affect the 1-year outcome of surgery. CONCLUSION: Obesity-related hypogonadotrophic hypogonadism is a reversible condition in the majority of obese men. It does not reduce the efficacy of bariatric surgery. Preoperative weight-adjusted normal values are recommended to avoid an incorrect diagnosis of hypogonadism in obese men. PMID- 24237303 TI - Towards reaching the target: clinical application of mesenchymal stem cells for diabetic foot ulcers. AB - Mesenchymal stem cells (MSCs) hold great promise for therapeutic application in non-healing ulcers and tissue regeneration because of their multi-lineage differentiation potential. MSCs delivered may migrate to the sites of injury and improve wound healing by stimulating angiogenesis and promoting revascularization. The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. It is associated with peripheral neuropathy and peripheral arterial occlusive disease (PAOD), which predispose patients to develop non-healing foot ulcers following minor trauma. A high rate of amputation exists among diabetic patients due to non-healing foot ulcers, which are a significant burden for the society despite new therapeutic protocols developed. In recent years, stem cell transplantation has been considered as a new therapeutic option for diabetic foot ulcers (DFUs). The regeneration potential of MSCs has been demonstrated in the experimental and clinical trials. Here we review the potential efficacy and systematic use of MSCs for the treatment of non-healing DFUs, current advances, MSC delivery systems, and possible options to enhance the therapeutic potential of stem cell for wound healing. PMID- 24237304 TI - Effects of Si/Al ratio on the distribution of framework Al and on the rates of alkane monomolecular cracking and dehydrogenation in H-MFI. AB - The aim of this study was to investigate the influence of Si/Al ratio on the locations of exchangeable cations in H-MFI and on the monomolecular cracking and dehydrogenation reactions of n-butane. On the basis of UV-visible spectroscopic analysis of Co(II) exchanged into MFI, it was inferred that the fraction of Co(II) (and, by extension, Bronsted protons) located at channel intersections relative to straight and sinusoidal channels increases with increasing Al content. Concurrently, turnover frequencies for all monomolecular reactions, and the selectivities to dehydrogenation versus cracking and to terminal cracking versus central cracking, generally increased. The changes in selectivity with Al content are consistent with the finding that the transition-state geometry for dehydrogenation is bulky and resembles a product state, and should therefore exhibit a stronger preference to occur at channel intersections relative to cracking. Increases in turnover frequencies are attributed partly to increases in intrinsic activation entropies that compensate for concurrent increases in intrinsic activation energies, most strongly for dehydrogenation and terminal cracking, resulting in increased selectivity to these reactions at higher Al content. This interpretation contrasts with the view that intrinsic activation barriers are constant. It is also observed that isobutene inhibits the rate of n butane dehydrogenation. Theoretical calculations indicate that this effect originates from adsorption of isobutene at the channel intersections. Because cracking reaction rates are not affected by the presence of isobutene, this result suggests that the preference of dehydrogenation to occur at channel intersections is much stronger than the preference for cracking to occur at these locations. PMID- 24237305 TI - NF-kappaB mediated miR-21 regulation in cardiomyocytes apoptosis under oxidative stress. AB - Oxidative stress, defined as an excess production of reactive oxygen species (ROS), is shown to play an important role in the pathophysiology of cardiac remodeling including cell death and contractile dysfunction. Therefore, the balance between ROS production and removal of excess ROS is essential in maintaining the redox state and homeostasis balance in the cell. The increased ROS further activates nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor and promotes cell death. Recently, microRNAs (miRNAs) have been identified as critical regulators of various pathophysiological processes of cardiac remodeling; however, NF-kappaB-mediated miRNA's role in cardiomyocytes under oxidative stress remains undetermined. The miR-21 has been implicated in diverse cardiac remodeling; but, NF-kappaB-mediated miR-21 modulation in oxidative stress is currently unknown. Neonatal cardiomyocytes were transfected with IkappaBalpha mutant, miR-21 mimetic, and inhibitors separately, and were challenged with H2O2. The target gene, programmed cell death 4 (PDCD4), ROS activity, and NF-kappaB translocation were analyzed. Our results indicated that NF-kappaB positively regulated miR-21 expression under oxidative stress, and PDCD4 was a direct target for miR-21. NF-kappaB further regulated the expression of PDCD4 in H2O2-induced oxidative stress. Moreover, H2O2-induced ROS activity and cardiomyocytes apoptosis were partly protected by overexpression of miR-21 and displayed an important role in ROS-mediated cardiomyocytes injury. We evaluated a critical role of NF-kappaB-mediated miR-21 modulation in H2O2-induced oxidative stress in cardiomyocytes by targeting PDCD4. Our data may provide a new insight of miR-21's role in cardiac diseases primarily mediated by ROS. PMID- 24237306 TI - Nitrate reductase-mediated early nitric oxide burst alleviates oxidative damage induced by aluminum through enhancement of antioxidant defenses in roots of wheat (Triticum aestivum). AB - * Nitric oxide (NO) is an important signaling molecule involved in the physiological processes of plants. The role of NO release in the tolerance strategies of roots of wheat (Triticum aestivum) under aluminum (Al) stress was investigated using two genotypes with different Al resistances. * An early NO burst at 3 h was observed in the root tips of the Al-tolerant genotype Jian-864, whereas the Al-sensitive genotype Yang-5 showed no NO accumulation at 3 h but an extremely high NO concentration after 12 h. Stimulating NO production at 3 h in the root tips of Yang-5 with the NO donor relieved Al-induced root inhibition and callose production, as well as oxidative damage and ROS accumulation, while elimination of the early NO burst by NO scavenger aggravated root inhibition in Jian-864. * Synthesis of early NO in roots of Jian-864 was mediated through nitrate reductase (NR) but not through NO synthase. Elevated antioxidant enzyme activities were induced by Al stress in both wheat genotypes and significantly enhanced by NO donor, but suppressed by NO scavenger or NR inhibitor. * These results suggest that an NR-mediated early NO burst plays an important role in Al resistance of wheat through modulating enhanced antioxidant defense to adapt to Al stress. PMID- 24237307 TI - Illness experiences in middle-aged adults with early-stage knee osteoarthritis: findings from a qualitative study. AB - AIM: To understand the illness experiences of middle-aged adults with early knee osteoarthritis. BACKGROUND: Knee osteoarthritis is one of the most common causes of lower limb disability in middle-aged adults and older people. Nurses lack understanding of the illness experiences of middle-aged patients who were confirmed to have early knee osteoarthritis and of how they manage the disease in Taiwan. DESIGN: A qualitative descriptive design was applied. METHODS: Participants with knee osteoarthritis, aged 40-55 years, were recruited by purposive sampling (n = 17). The data were collected through semi-structured interviews from July-December 2010. All interview transcripts were analysed using qualitative inductive content analysis to identify key themes. FINDINGS: Illness experiences of the seventeen participants were classified into three major themes: (i) unfamiliarity with osteoarthritis; (ii) effects on daily life; and (iii) protection and alleviation. The three main themes occurred repeatedly and affected the life experiences of the patients. CONCLUSIONS: This study indicates that patients with osteoarthritis have insufficient knowledge related to disease process and they do not know how to cope effectively. They need healthcare providers to supply them with adequate osteoarthritis disease information. Nurses should also develop interventions in their practices and guide patients to use suitable techniques to improve the functional status of their knee joint(s). PMID- 24237310 TI - Choledochoduodenal fistula after biliary metallic stent placement for pancreatic cancer. PMID- 24237311 TI - Artificial biometric finger driven by shape-memory alloy wires. AB - This paper presents the design and testing of an artificial finger based partly on biomechanics. The prototype was manufactured in acrylonitrile butadiene styrene plastic using a rapid prototyping three-dimensional printer. The flexing of the finger was realized by Ni-Ti shape-memory alloy (SMA) wires with diameters of 0.3 mm, activated by resistive heating. The results obtained show the new prototype to be superior in performance, mainly in terms of angles of rotation of the phalanges, compared with some SMA fingers discussed in the literature. PMID- 24237309 TI - Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting. AB - Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with <=200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems. PMID- 24237312 TI - Role of nitrite in the photochemical formation of radicals in the snow. AB - Photochemical reactions in snow can have an important impact on the composition of the atmosphere over snow-covered areas as well as on the composition of the snow itself. One of the major photochemical processes is the photolysis of nitrate leading to the formation of volatile nitrogen compounds. We report nitrite concentrations determined together with nitrate and hydrogen peroxide in surface snow collected at the coastal site of Barrow, Alaska. The results demonstrate that nitrite likely plays a significant role as a precursor for reactive hydroxyl radicals as well as volatile nitrogen oxides in the snow. Pollution events leading to high concentrations of nitrous acid in the atmosphere contributed to an observed increase in nitrite in the surface snow layer during nighttime. Observed daytime nitrite concentrations are much higher than values predicted from steady-state concentrations based on photolysis of nitrate and nitrite indicating that we do not fully understand the production of nitrite and nitrous acid in snow. The discrepancy between observed and expected nitrite concentrations is probably due to a combination of factors, including an incomplete understanding of the reactive environment and chemical processes in snow, and a lack of consideration of the vertical structure of snow. PMID- 24237313 TI - Agreement between children aged 5-6 years and their mothers in rating child oral health-related quality of life. AB - BACKGROUND: Studies have assessed parent-child agreement on ratings of school aged children's OHRQoL. There are, however, no studies on children younger than 7 years of age. AIMS: The aim was to assess the agreement between children aged 5-6 years and their mothers regarding child's oral health-related quality of life (OHRQoL). DESIGN: In this cross-sectional study, a total of 298 mother-child pairs (MCP), seeking the pediatric dental screening at the Dental School, University of Sao Paulo, completed the Brazilian version of the Scale of Oral Health Outcomes for 5-year-old children (SOHO-5), validated for children aged 5-6 years in Brazil. Agreement between total and items' scores was assessed using comparison and correlation analyses, by comparing the mean directional differences and by computing the intraclass correlation coefficient (ICC) values, respectively. RESULTS: The mean directional difference in the total scores was 0.13 (CI 95% -0.076; 0.338) and therefore not significant for MCP. The mean absolute difference for MCP was 1.26, representing 11% of the maximum possible score. The ICC for total score was 0.84 (CI 95% 0.798; 0.867) for MCP. CONCLUSIONS: Mothers do rate their young children's OHRQoL similarly to children's self-reports. When assessing OHRQoL of children aged 5-6 years, mothers may be reliable proxies for their young children. PMID- 24237314 TI - FairyTALE: a high-throughput TAL effector synthesis platform. AB - Recombinant transcription activator-like effectors (TALEs) have been effectively used for genome editing and gene regulation applications. Due to their remarkable modularity, TALEs can be tailored to specifically target almost any user-defined DNA sequences. Here, we introduce fairyTALE, a liquid phase high-throughput TALE synthesis platform capable of producing TALE-nucleases, activators, and repressors that recognize DNA sequences between 14 and 31 bp. It features a highly efficient reaction scheme, a flexible functionalization platform, and fully automated robotic liquid handling that enable the production of hundreds of expression-ready TALEs within a single day with over 98% assembly efficiency at a material cost of just $5 per TALE. As proof of concept, we synthesized and tested 90 TALEs, each recognizing 27 bp, without restrictions on their sequence composition. 96% of these TALEs were found to be functional, while sequencing confirmation revealed that the nonfunctional constructs were all correctly assembled. PMID- 24237315 TI - R&D transformation and value-based innovation. PMID- 24237316 TI - A framework for pharmaceutical value-based innovations. AB - The rapidity of change and increasing complexity of today's healthcare environment dictates that pharmaceutical companies refine their drug development process to ensure that products provide maximal value to consumers. Innovation should receive the support and encouragement it deserves but the balance between cost of therapy and enhanced benefits to the end users, the patients, must not be compromised. The health or quality-of-life outcomes that therapies are likely to achieve need to be clearly stated for patients so they know what to expect before beginning treatment. A drug development program that incorporates principles of 'patient-centered medicine' early on can help define the true value of a health technology. This demands not only demonstrating value as measured by actual patient experience and patient-reported outcomes, but understanding the unmet needs of multiple stakeholders: what is their perception of what represents value? What factors impact healthcare coverage decisions? In this paper, we describe an illustrative framework designed to weave 'patient-centric' medical and real-world evidence into the phases of research and development. This evidence and value development framework works iteratively, providing useful insights parallel to product development from early phase to life-cycle management while forming a progressive evidence chain throughout the phases of research and development. This in turn leads to the creation of value-based innovation with robust foundational evidence for clinical decisions, postlaunch coverage and reimbursement evaluations. PMID- 24237317 TI - Integrating scientific and real-world evidence within and beyond the drug development process. AB - Newly developed healthcare treatments face a complex environment with many stakeholders who can accelerate or decelerate adoption, most notably the healthcare system payers. Understanding and integrating their needs earlier in clinical development will ensure a smoother transition from bench to bedside. This paper describes a new approach to shaping a more effective complementary process of 'value' evidence generation both in and outside the clinical drug development process. We propose that biopharmaceutical companies consider bringing new solutions to market by marshaling cross-functional approaches to what we term an evidence-definition phase, evidence-generation phase and evidence translation phase to drug and technology research and development. The organization of ongoing discovery, evaluation and translation with a 'real- world' perspective should provide a more streamlined approach to ensure both regulatory and eventual marketplace success. PMID- 24237318 TI - Integrating new approaches for clinical development: translational research and relative effectiveness. AB - Translational research and relative effectiveness are being incorporated into drug development programs to meet the demands for more robust evidence generation to support the value of new therapies. Translational research includes translating basic research into clinical practice, controlled clinical trials into potential clinical implications, evidence-based guidelines into routine clinical practice and standard practices into population health. These research concepts link with real-world outcomes, and feed into each other to improve the efficiency of research. Translational research can run into road blocks in terms of conveying the added or comparative value of research or during adoption into clinical practice. Understanding these roadblocks and developing solutions are important for success. Comparative effectiveness research can be a useful research technique to accomplish many translational medicine goals. These studies generally include heterogeneous patient populations and evaluate outcomes of relevance to payers and health technology assessors. Comparative effectiveness research can be used in drug development; different methodologies may be useful in different phases. In this article, suggestions and examples of successful use of comparative effectiveness studies are provided. Translational research and comparative effectiveness research, although clearly independent concepts, can provide a focused approach to drug development, resulting in products entering the market that bring added benefit to patients and the healthcare system overall. PMID- 24237319 TI - Nucleopalladation triggering the oxidative Heck reaction: a general strategy to diverse beta-indole ketones. AB - A simple and efficient palladium-catalyzed oxidative coupling between 2-alkynyl anilines and allylic alcohols is described by using cheap and green dioxygen as the oxidant. These cross-couplings have a large functional group tolerance and are of higher reactivity toward electron nonbaised allylic alcohols. The resultant beta-indole ketones are readily converted to pharmaceutically significant beta-indole alcohol/amine and pyrrolo[2,1-a]isoquinolines. PMID- 24237320 TI - Reinforcement of teeth with simulated coronal fracture and immature weakened roots using resin composite cured by a modified layering technique. AB - OBJECTIVE: The purpose of this study was to evaluate the strengthening effect of resin composite, cured by a modified layering protocol, for teeth with simulated coronal fracture and weakened immature roots. METHODS: Fifty maxillary teeth were decoronated and their apices sectioned to standardize the length to 12 mm. Prepared teeth were equally distributed into five groups. Group 1VF root apices were flared with Pesso drills up to size 6. The roots were flared until a dentin thickness of only 1 +/- 0.2 mm remained. Root ends were filled with mineral trioxide aggregate. The canals were backfilled with Vertise Flow following a modified layering protocol using two light-transmitting posts size 6 and 3. Next, a DT light post size 2 was cemented using the same material. Groups 2TS/MF and 3ED/PF were prepared and cured in the same way as group 1VF but filled with Clearfil Tri-S Bond/Majesty Flow and ED Primer II/Panavia F2.0 respectively. Group 4UF was similarly prepared but left unfilled (control). In group 5NW, roots were unflared but similarly filled as in group 3ED/PF. After 24 hours of storage, the fracture load was measured. The degree of cure for each tested material was indirectly measured using microhardness at different root levels (cervical, middle, and apical). Data were analyzed using one-way analysis of variance followed by Newman-Keuls post hoc test. RESULTS: Fracture load results revealed that groups 1VF and 2TS/MF had no statistically significant difference from group 5NW (p>0.05). For each tested material, no significant difference was found among microhardness values at different root levels. CONCLUSION: It may be possible to reinforce the teeth with coronal fracture and immature weakened roots to be comparable with unweakened ones when composite is applied and cured by the modified layering technique. PMID- 24237321 TI - Synthesis and reactivity of a transient, terminal nitrido complex of rhodium. AB - Irradiation of rhodium(II) azido complex [Rh(N3){N(CHCHPtBu2)2}] allowed for the spectroscopic characterization of the first reported rhodium complex with a terminal nitrido ligand. DFT computations reveal that the unpaired electron of rhodium(IV) nitride complex [Rh(N){N(CHCHPtBu2)2}] is located in an antibonding Rh-N pi* bond involving the nitrido moiety, thus resulting in predominant N radical character, in turn providing a rationale for its transient nature and observed nitride coupling to dinitrogen. PMID- 24237323 TI - Personal profile: interview with Richard Barker. PMID- 24237322 TI - Glucose inhibits root meristem growth via ABA INSENSITIVE 5, which represses PIN1 accumulation and auxin activity in Arabidopsis. AB - Glucose functions as a hormone-like signalling molecule that modulates plant growth and development in Arabidopsis thaliana. However, the role of glucose in root elongation remains elusive. Our study demonstrates that high concentrations of glucose reduce the size of the root meristem zone by repressing PIN1 accumulation and thereby reducing auxin levels. In addition, we verified the involvement of ABA INSENSITIVE 5 (ABI5) in this process by showing that abi5-1 is less sensitive to glucose than the wild type, whereas glucose induces ABI5 expression and the inducible overexpression of ABI5 reduces the size of the root meristem zone. Furthermore, the inducible overexpression of ABI5 in PIN1::PIN1 GFP plants reduces the level of PIN1-GFP, but glucose reduces the level of PIN1 GFP to a lesser extent in abi5-1 PIN1::PIN1-GFP plants than in the PIN1::PIN1-GFP control, suggesting that ABI5 is involved in glucose-regulated PIN1 accumulation. Taken together, our data suggest that ABI5 functions in the glucose-mediated inhibition of the root meristem zone by repressing PIN1 accumulation, thus leading to reduced auxin levels in roots. PMID- 24237324 TI - Dynamic solvation and coupling of the hydration shell of Zn(II)-substituted cytochrome c in the presence of guanidinium ions. AB - The fluorescence Stokes shift (FSS) response of Zn(II)-substituted cytochrome c (ZnCytc) is transformed from a monotonic red-shifting response in water to a bidirectional response with much slower time constants in the presence of low concentrations of guanidinium (Gdm(+)) ions. The FSS response in water observed over the 100 ps to 10 ns range has two exponential components with time constants of 135 ps and 1.6 ns that account for a total shift of 30 cm(-1), about one-half of the solvation reorganization energy. In contrast, in the presence of only 0.25 M Gdm(+), the FSS response initially shifts 21 cm(-1) to the blue with a 820 ps time constant and then shifts 60 cm(-1) back to the red with a 3.5 ns time constant. The effect of Gdm(+) on the FSS response effectively saturates at 1.0 M, well below the 1.75 M midpoint of the two-state unfolding transition. These results establish that the FSS response in ZnCytc includes a significant contribution from the surrounding hydration shell, which assumes a perturbed hydrogen-bonding network owing to the binding of Gdm(+) ions to the protein surface. The blue-shifting part of the FSS response arises from a light-induced conformational change that expands the protein- and solvent-derived cavity around the excited-state Zn(II) porphyrin. This non-polar part of the solvation response is enhanced in the presence of Gdm(+) because the protein/solvent surroundings of the Zn(II) porphyrin are effectively more flexible than in water. The enhanced flexibility in the presence of Gdm(+) increases the amplitudes and accordingly lengthens the correlation time scales for the protein and hydration-shell fluctuations that contribute to the FSS response. PMID- 24237325 TI - Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation. AB - Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (~27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes. PMID- 24237326 TI - Pharmacokinetics and efficiency of brain targeting of ginsenosides Rg1 and Rb1 given as Nao-Qing microemulsion. AB - Nao-Qing solution has been shown to be clinically effective in the treatment of acute ischemic stroke (AIS). The purpose of this study was to improve the pharmacokinetics and brain uptake of Nao-Qing, administered as an oil-in-water microemulsion. Sprague-Dawley (SD) rats were given Nao-Qing microemulsion by intranasal or intragastric routes. Samples of blood, brain, heart, liver, lung and kidney were collected at pre-determined time intervals, and the contents of ginsenosides Rg1 and Rb1 (active ingredients of the Nao-Qing microemulsion) were analyzed by high-performance liquid chromatography (HPLC). The results showed that contents of ginsenosides Rg1 and Rb1 in Nao-Qing microemulsion was 8475.13 +/- 54.61 MUg/ml and 6633.42 +/- 527.27 MUg/ml, respectively, and that the particle size, pH and viscosity of the microemulsion were 19.9 +/- 5.07 nm, 6.1 and 3.056 * 10(-3 )Pas, respectively. Absorption of ginsenoside Rg1 was higher than that of ginsenoside Rb1, which was barely detectable after intragastric administration; furthermore, the concentration of ginsenoside Rg1 in blood and other tissues at each time point was lower for intragastric than for intranasal administration. Compared with intragastric administration, intranasal administration resulted in a shorter tmax (0.08 versus 1 h), a higher Cmax (16.65 versus 11.29 MUg/ml), and a higher area under the concentration-time curve (AUC) (592.91 versus 101.70 MUgch/ml) in the brain. The relative rates of uptake (Re) and the ratio of peak concentration (Ce) in the brain were 126.31% and 147.48% for ginsenoside Rg1, respectively. These data illustrate that intranasal administration can promote the absorption of drugs in Nao-Qing microemulsion and achieve fast effect. PMID- 24237327 TI - Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancement. AB - Phyllanthin, a poorly water-soluble herbal active component from Phyllanthus amarus, exhibited a low oral bioavailability. This study aims at formulating self microemulsifying drug delivery systems (SMEDDS) containing phyllanthin and evaluating their in-vitro and in-vivo performances. Excipient screening was carried out to select oil, surfactant and co-surfactant. Formulation development was based on pseudo-ternary phase diagrams and characteristics of resultant microemulsions. Influences of dilution, pH of media and phyllanthin content on droplet size of the resultant emulsions were studied. The optimized phyllanthin loaded SMEDDS formulation (phy-SMEDDS) and the resultant microemulsions were characterized by viscosity, self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. In-vitro dissolution and oral bioavailability in rats of phy-SMEDDS were studied and compared with those of plain phyllanthin. Phy-SMEDDS consisted of phyllanthin/Capryol 90/Cremophor RH 40/Transcutol P (1.38:39.45:44.38:14.79) in % w/w. Phy-SMEDDS could be emulsified completely within 6 min and formed fine microemulsions, with average droplet range of 27-42 nm. Phy-SMEDDS was robust to dilution and pH of dilution media while the resultant emulsion showed no phase separation or drug precipitation after 8 h dilution. The release of phyllanthin from phy-SMEDDS capsule was significantly faster than that of plain phyllanthin capsule irrespective of pH of dissolution media. Phy-SMEDDS was found to be stable for at least 6 months under accelerated condition. Oral absorption of phyllanthin in rats was significantly enhanced by SMEDDS as compared with plain phyllanthin. Our study indicated that SMEDDS for oral delivery of phyllanthin could be an option to enhance its bioavailability. PMID- 24237328 TI - Spray drying formulation of albendazole microspheres by experimental design. In vitro-in vivo studies. AB - Both an experimental design and optimization techniques were carried out for the development of chitosan-pectin-carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60 min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug. PMID- 24237329 TI - Life quality and health in adolescents and emerging adults with epilepsy during the years of transition: a scoping review. AB - AIMS: The aims of this study were to (1) search the literature in order to identify the challenges facing adolescents and emerging adults with epilepsy; and (2) categorize these issues within both the framework of the International Classification of Functioning, Disability and Health (ICF) and an empirical model of quality of life (QOL) in childhood epilepsy. METHOD: We systematically searched PsycINFO, Ovid MEDLINE and Web of Science for studies reporting on QOL and health identified in people with epilepsy aged 12 to 29 years. Studies were limited to those that were published in the last 20 years in English, presenting the patient perspective. Data were extracted and charted using a descriptive analytical method. Identified issues were classified according to the ICF and QOL frameworks. RESULTS: Fifty four studies were identified. Another 62 studies with potentially useful information were included as an addendum. The studies highlight a range of psychosocial issues emphasizing peer acceptance, social isolation, and feelings of anxiety, fear, and sadness. INTERPRETATION: The ICF and QOL constructs represent useful starting points in the analytical classification of the potential challenges faced by adolescents with epilepsy. Progress is needed on fully classifying issues not included under these frameworks. We propose to expand these frameworks to include comorbidities, impending medical interventions, and concerns for future education, employment, marriage, dignity, and autonomy. PMID- 24237330 TI - Genomics: from persons to populations and back again. PMID- 24237331 TI - The cancer epigenome. PMID- 24237333 TI - Wheat genomics and the ambitious targets for future wheat production. PMID- 24237332 TI - Viruses: unlocking the greatest biodiversity on Earth. PMID- 24237334 TI - Understanding salmonid biology from the Atlantic salmon genome. PMID- 24237335 TI - The Green Revolution 2.0: the potential of algae for the production of biofuels and bioproducts. PMID- 24237336 TI - Livestock and the promise of genomics. AB - The emergence of the middle class in countries such as Brazil, Russia, India, and China is resulting in increasing global demand for animal-based food products. This increase represents a unique opportunity for Canadian livestock producers to export their products to new markets and expand Canada's reputation as a global provider of safe and highest quality food items. This article has two major themes. First, current Canadian contributions to livestock genomics in the cattle and swine industries are outlined. Second, important future opportunities are discussed, including the high throughput collection of phenotypic data, development of environmentally friendly livestock, emergence of decision support software, and the use of Web 2.0. Through the use of genomic technologies, livestock producers can not only ensure that the nutritional demands of Canada are secured, but also play a pivotal role in ensuring the rest of the world is fed as well. Furthermore, investment through initiatives led by Genome Canada has ensured that Canada is favorably positioned to contribute cutting-edge solutions to meet this global challenge. Ultimately, genomic-based innovations will enable producers to increase efficiency, lower production costs, decrease the use of prophylactics, and limit the expenditure of resources. PMID- 24237337 TI - The impact of a moderate chronic temperature increase on spleen immune-relevant gene transcription depends on whether Atlantic cod (Gadus morhua) are stimulated with bacterial versus viral antigens. AB - Exposure to elevated temperature is an inherent feature of Atlantic cod (Gadus morhua) sea-cage culture in some regions (e.g., Newfoundland) and may also become an increasingly prevalent challenge for wild fish populations because of accelerated climate change. Therefore, understanding how elevated temperatures impacts the immune response of this commercially important species may help to reduce the potential negative impacts of such challenges. Previously, we investigated the impacts of moderately elevated temperature on the antiviral responses of Atlantic cod (Hori et al. 2012) and reported that elevated temperature modulated the spleen transcriptome response to polyriboinosinic polyribocytidylic acid (pIC, a viral mimic). Herein, we report a complementary microarray study that investigated the impact of the same elevated temperature regime on the Atlantic cod spleen transcriptome response to intraperitoneal (IP) injection of formalin-killed Aeromonas salmonicida (ASAL). Fish were held at two different temperatures (10 degrees C and 16 degrees C) prior to immune stimulation and sampled 6 and 24 h post-injection (HPI). In this experiment, we identified 711 and 666 nonredundant ASAL-responsive genes at 6HPI and 24HPI, respectively. These included several known antibacterial genes, including hepcidin, cathelicidin, ferritin heavy subunit, and interleukin 8. However, we only identified 15 differentially expressed genes at 6HPI and 2 at 24HPI (FDR 1%) when comparing ASAL-injected fish held at 10 degrees C versus 16 degrees C. In contrast, the same comparisons with pIC-injected fish yielded 290 and 339 differentially expressed genes (FDR 1%) at 6HPI and 24HPI, respectively. These results suggest that moderately elevated temperature has a lesser effect on the Atlantic cod spleen transcriptome response to ASAL (i.e., the antibacterial response) than to pIC (i.e., antiviral response). Thus, the impacts of high temperatures on the cod's immune response may be pathogen dependent. PMID- 24237338 TI - Effects of introgression on the genetic population structure of two ecologically and economically important conifer species: lodgepole pine (Pinus contorta var. latifolia) and jack pine (Pinus banksiana). AB - Forest trees exhibit a remarkable range of adaptations to their environment, but as a result of frequent and long-distance gene flow, populations are often only weakly differentiated. Lodgepole and jack pine hybridize in western Canada, which adds the opportunity for introgression through hybridization to contribute to population structure and (or) adaptive variation. Access to large sample size, high density SNP datasets for these species would improve our ability to resolve population structure, parameterize introgression, and separate the influence of demography from adaptation. To accomplish this, 454 transcriptome reads for lodgepole and jack pine were assembled using Newbler and MIRA, the assemblies mined for SNPs, and 1536 SNPs were selected for typing on lodgepole pine, jack pine, and their hybrids (N = 536). We identified population structure using both Bayesian clustering and discriminate analysis of principle components. Introgressed SNP loci were identified and their influence on observed population structure was assessed. We found that introgressed loci resulted in increased differentiation both within lodgepole and jack pine populations. These findings are timely given the recent mountain pine beetle population expansion in the hybrid zone, and will facilitate future studies of adaptive traits in these ecologically important species. PMID- 24237339 TI - Association analysis for feed efficiency traits in beef cattle using preserved haplotypes. AB - This study reports a genome wide scan for chromosome regions and their haplotypes that significantly associated with average daily gain (ADG), dry matter intake (DMI), and residual feed intake (RFI) in beef cattle. The study used data from 597 Angus, 450 Charolais, and 616 crossbred beef cattle, and the Illumina Bovine SNP50 beadchip. Extended haplotype homozygosity was used to identify chromosome regions that had been recently selected for in the three groups of animals. Such regions in the crossbreds were tested for association with ADG, DMI, and RFI. At false discovery rates of 5% and 10%, there were six and eight chromosome regions showing significant associations with the traits, respectively. At nominal significance levels (at least P < 0.05), 23 regions with a total number of 31 haplotypes were found significantly associated with at least one of the three traits. The proportion of phenotypic variance explained by these 23 regions varied depending on the trait; the highest proportion for ADG, DMI, and RFI was 13.50%, 9.92%, and 2.64%, respectively. Most of the haplotypes affected single traits, except for GAA (BTA4), GCG (BTA7), and TAGT (BTA12) that affected multiple traits. Thirty-six quantitative trait loci for 16 production traits, from the current literature, covered fully or in part the 23 chromosome regions. The findings from this study might be an important contribution to the current knowledge of the beef cattle genome and to the effective identification of causative genes associated with important traits in cattle. PMID- 24237340 TI - Whole genome sequencing of Gir cattle for identifying polymorphisms and loci under selection. AB - Genetic variation in Gir cattle (Bos indicus) has so far not been well characterized. In this study, we used whole genome sequencing of three Gir bulls and a pooled sample from another 11 bulls to identify polymorphisms and loci under selection. A total of 9 990 733 single nucleotide polymorphisms (SNPs) and 604 308 insertion/deletions (indels) were discovered in Gir samples, of which 62.34% and 83.62%, respectively, are previously unknown. Moreover, we detected 79 putative selective sweeps using the sequence data of the pooled sample. One of the most striking sweeps harbours several genes belonging to the cathelicidin gene family, such as CAMP, CATHL1, CATHL2, and CATHL3, which are related to pathogen- and parasite-resistance. Another interesting region harbours genes encoding mitogen-activated protein kinases, which are involved in directing cellular responses to a variety of stimuli, such as osmotic stress and heat shock. These findings are particularly interesting because Gir is resistant to hot temperatures and tropical diseases. This initial selective sweep analysis of Gir cattle has revealed a number of loci that could be important for their adaptation to tropical climates. PMID- 24237341 TI - Metagenomic analysis of an anaerobic alkane-degrading microbial culture: potential hydrocarbon-activating pathways and inferred roles of community members. AB - A microbial community (short-chain alkane-degrading culture, SCADC) enriched from an oil sands tailings pond was shown to degrade C6-C10 alkanes under methanogenic conditions. Total genomic DNA from SCADC was subjected to 454 pyrosequencing, Illumina paired-end sequencing, and 16S rRNA amplicon pyrotag sequencing; the latter revealed 320 operational taxonomic units at 5% distance. Metagenomic sequences were subjected to in-house quality control and co-assembly, yielding 984 086 contigs, and annotation using MG-Rast and IMG. Substantial nucleotide and protein recruitment to Methanosaeta concilii, Syntrophus aciditrophicus, and Desulfobulbus propionicus reference genomes suggested the presence of closely related strains in SCADC; other genomes were not well mapped, reflecting the paucity of suitable reference sequences for such communities. Nonetheless, we detected numerous homologues of putative hydrocarbon succinate synthase genes (e.g., assA, bssA, and nmsA) implicated in anaerobic hydrocarbon degradation, suggesting the ability of the SCADC microbial community to initiate methanogenic alkane degradation by addition to fumarate. Annotation of a large contig revealed analogues of the ass operon 1 in the alkane-degrading sulphate-reducing bacterium Desulfatibacillum alkenivorans AK-01. Despite being enriched under methanogenic fermentative conditions, additional metabolic functions inferred by COG profiling indicated multiple CO(2) fixation pathways, organic acid utilization, hydrogenase activity, and sulphate reduction. PMID- 24237342 TI - Microbial community and potential functional gene diversity involved in anaerobic hydrocarbon degradation and methanogenesis in an oil sands tailings pond. AB - Oil sands tailings ponds harbor large amounts of tailings resulting from surface mining of bitumen and consist of water, sand, clays, residual bitumen, and hydrocarbon diluent. Oxygen ingress in these ponds is limited to the surface layers, causing most hydrocarbon degradation to be catalyzed by anaerobic, methanogenic microbial communities. This causes the evolution of large volumes of methane of up to 10(4) m(3)/day. A pyrosequencing survey of 16S rRNA amplicons from 10 samples obtained from different depths indicated the presence of a wide variety of taxa involved in anaerobic hydrocarbon degradation and methanogenesis, including the phyla Proteobacteria, Euryarchaeota, Firmicutes, Actinobacteria, Chloroflexi, and Bacteroidetes. Metagenomic sequencing of DNA isolated from one of these samples indicated a more diverse community than indicated by the 16S rRNA amplicon survey. Both methods indicated the same major phyla to be present. The metagenomic dataset indicated the presence of genes involved in the three stages of anaerobic aromatic hydrocarbon degradation, including genes for enzymes of the peripheral (upper), the central (lower), and the methanogenesis pathways. Upper pathway genes showed broad phylogenetic affiliation (Proteobacteria, Firmicutes, and Actinobacteria), whereas lower pathway genes were mostly affiliated with the Deltaproteobacteria. Genes for both hydrogenotrophic and acetotrophic methanogenesis were also found. The wide variety of taxa involved in initial hydrocarbon degradation through upper pathways may reflect the variety of residual bitumen and diluent components present in the tailings pond. PMID- 24237343 TI - Neuregulin 1-alpha regulates phosphorylation, acetylation, and alternative splicing in lymphoblastoid cells. AB - Neuregulins (NRGs) are signaling molecules involved in various cellular and developmental processes. Abnormal expression and (or) genomic variations of some of these molecules, such as NRG1, have been associated with disease conditions such as cancer and schizophrenia. To gain a comprehensive molecular insight into possible pathways/networks regulated by NRG1-alpha, we performed a global expression profiling analysis on lymphoblastoid cell lines exposed to NRG1-alpha. Our data show that this signaling molecule mainly regulates coordinated expression of genes involved in three processes: phosphorylation, acetylation, and alternative splicing. These processes have fundamental roles in proper development and function of various tissues including the central nervous system (CNS)--a fact that may explain conditions associated with NRG1 dysregulations such as schizophrenia. The data also suggest NRG1-alpha regulates genes (FBXO41) and miRNAs (miR-33) involved in cholesterol metabolism. Moreover, RPN2, a gene already shown to be dysregulated in breast cancer cells, is also differentially regulated by NRG1-alpha treatment. PMID- 24237345 TI - Family-based exome-sequencing approach identifies rare susceptibility variants for lithium-responsive bipolar disorder. AB - Bipolar disorder (BD) is a psychiatric condition characterized by the occurrence of at least two episodes of clinically disturbed mood including mania and depression. A vast literature describing BD studies suggests that a strong genetic contribution likely underlies this condition; heritability is estimated to be as high as 80%. Many studies have identified BD susceptibility loci, but because of the genetic and phenotypic heterogeneity observed across individuals, very few loci were subsequently replicated. Research in BD genetics to date has consisted of classical linkage or genome-wide association studies, which have identified candidate genes hypothesized to present common susceptibility variants. Although the observation of such common variants is informative, they can only explain a small fraction of the predicted BD heritability, suggesting a considerable contribution would come from rare and highly penetrant variants. We are seeking to identify such rare variants, and to increase the likelihood of being successful, we aimed to reduce the phenotypic heterogeneity factor by focusing on a well-defined subphenotype of BD: excellent response to lithium monotherapy. Our group has previously shown positive response to lithium therapy clusters in families and has a consistent clinical presentation with minimal comorbidity. To identify such rare variants, we are using a targeted exome capture and high-throughput DNA sequencing approach, and analyzing the entire coding sequences of BD affected individuals from multigenerational families. We are prioritizing rare variants with a frequency of less than 1% in the population that segregate with affected status within each family, as well as being potentially highly penetrant (e.g., protein truncating, missense, or frameshift) or functionally relevant (e.g., 3'UTR, 5'UTR, or splicing). By focusing on rare variants in a familial cohort, we hope to explain a significant portion of the missing heritability in BD, as well as to narrow our current insight on the key biochemical pathways implicated in this complex disorder. PMID- 24237344 TI - Public attitudes towards genomic risk profiling as a component of routine population screening. AB - Including low penetrance genomic variants in population-based screening might enable personalization of screening intensity and follow up. The application of genomics in this way requires formal evaluation. Even if clinically beneficial, uptake would still depend on the attitudes of target populations. We developed a deliberative workshop on two hypothetical applications (in colorectal cancer and newborn screening) in which we applied stepped, neutrally-framed, information sets. Data were collected using nonparticipant observation, free-text comments by individual participants, and a structured survey. Qualitative data were transcribed and analyzed using thematic content analysis. Eight workshops were conducted with 170 individuals (120 colorectal cancer screening and 50 newborn screening for type 1 diabetes). The use of information sets promoted informed deliberation. In both contexts, attitudes appeared to be heavily informed by assessments of the likely validity of the test results and its personal and health care utility. Perceived benefits included the potential for early intervention, prevention, and closer monitoring while concerns related to costs, education needs regarding the probabilistic nature of risk, the potential for worry, and control of access to personal genomic information. Differences between the colorectal cancer and newborn screening groups appeared to reflect different assessments of potential personal utility, particularly regarding prevention. PMID- 24237347 TI - Proceedings of a Meeting "Genomics: The Power and the Promise", 27-28 November 2012, Ottawa, Ontario, Canada. PMID- 24237348 TI - Liquid-phase combinatorial library synthesis: recent advances and future perspectives. AB - Liquid-phase combinatorial library synthesis is commonly developed into the viable alternatives or adjunct across the broad spectrum of polymer-supported organic chemistry. It includes the use of soluble polymer supports in the combinatorial synthesis of peptides and small-molecular library compounds which act as catalyst and reagent supports. It also includes high throughput biological screening with generation and evaluation of chemical leads for drug discovery development. In this review, liquid-phase combinatorial library synthesis is shown as the most efficient method of choice for the synthesis of most of the combinatorial library compounds with specific approaches from different groups that state potentials of solution-phase combinatorial synthesis. PMID- 24237349 TI - The effect of self-efficacy, depression and symptom distress on employment status and leisure activities of liver transplant recipients. AB - AIM: To examine the effect of self-efficacy, subjective work ability, depression and symptom distress on and to provide a description of, the employment and leisure activities of liver transplant recipients. BACKGROUND: Return to work and leisure activities have become an important aspect of life for liver transplant recipients worldwide. An investigation of the factors that influence the employment status and leisure activities has been recommended as a means to help transplant recipients restore their productivity. DESIGN: This was a cross sectional, descriptive and correlational study in 2010. METHODS: A convenience sampling method was used. Data were collected using a set of questionnaires that were administered retrospectively. A total of 106 liver transplant patients were included in this study. RESULTS: The post-transplantation employment rate was 45.2%. The positive predictors of employment were higher subjective work ability and higher symptom distress. Gender (female), monthly family income (= 0.98), mean of daily differences (r >= 0.91), and mean amplitude of glycemic excursions (r >= 0.88). SFE correlated positively with CONGA at 1 h but not with the other indices and was inversely correlated with hypoglycemic episodes (Spearman's rho=-0.42), independently of the coefficient of variation and the Low Blood Glucose Index in a multivariate analysis (partial r= 0.34). CONCLUSIONS: PCP metrics are correlated with known GV indices and may be used for the study of CGM recording series in type 1 diabetes. SFE is a new risk marker for hypoglycemia. PMID- 24237388 TI - Evaluation of stochastic adjustment for glucose sensor bias during closed-loop insulin delivery. AB - BACKGROUND: In outpatient studies of closed-loop insulin delivery systems, it is not typically practical to obtain blood glucose measurements for an outcome measure. Using a continuous glucose monitoring (CGM) device as both part of the intervention and as the outcome in a clinical trial can give a biased estimate of the treatment effect. A stochastic adjustment has been proposed to correct this problem. MATERIALS AND METHODS: We performed Monte Carlo simulations to assess the performance of the stochastic adjustment in various scenarios where the CGM device was used passively and when it was used to inform insulin delivery. The resulting bias for using CGM to estimate the percentage of glucose values inside a target range was compared with and without the proposed stochastic adjustment. RESULTS: CGM bias for estimating the percentage of glucose values 70-180 mg/dL ranged from -6% to +4% in the various scenarios studied. In some circumstances, stochastic adjustment did indeed reduce this CGM bias. However, in other circumstances, stochastic adjustment made the bias worse. Stochastic adjustment tended to underestimate the true percentage of glucose values in range for most, but not all, scenarios considered in these simulations. CONCLUSIONS: Stochastic adjustment is not a general solution to the problem of CGM bias. The proposed adjustment relies on an implicit assumption that usually does not hold. The appropriate level of adjustment depends on how efficacious the closed-loop system is, which is not typically known in practice. PMID- 24237389 TI - Characterizing the plasticity of nitrogen metabolism by the host and symbionts of the hydrothermal vent chemoautotrophic symbioses Ridgeia piscesae. AB - Chemoautotrophic symbionts of deep sea hydrothermal vent tubeworms are known to provide their hosts with all their primary nutrition. While studies have examined how chemoautotrophic symbionts provide the association with nitrogen, fewer have examined if symbiont nitrogen metabolism varies as a function of environmental conditions. Ridgeia piscesae tubeworms flourish at Northeastern Pacific vents, occupy a range of microhabitats, and exhibit a high degree of morphological plasticity [e.g. long-skinny (LS) and short-fat (SF) phenotypes] that may relate to environmental conditions. This plasticity affords an opportunity to examine whether symbiont nitrogen metabolism varies among host phenotypes. LS and SF R. piscesae were recovered from the Axial and Main Endeavour Field hydrothermal vents. Nitrate and ammonium were quantified in Ridgeia blood, and the expression of key nitrogen metabolism genes, as well as stable nitrogen isotope ratios, was quantified in host branchial plume and symbiont-containing tissues. Nitrate and ammonium were abundant in the blood of both phenotypes though environmental ammonium concentrations were, paradoxically, lowest among individuals with the highest blood ammonium. Assimilatory nitrate reductase transcripts were always below detection, though in both LS and SF R. piscesae symbionts, we observed elevated expression of dissimilatory nitrate reductase genes, as well as symbiont and host ammonium assimilation genes. Site-specific differences in expression, along with tissue stable isotope analyses, suggest that LS and SF Ridgeia symbionts are engaged in both dissimilatory nitrate reduction and ammonia assimilation to varying degrees. As such, it appears that environmental conditions -not host phenotype-primarily dictates symbiont nitrogen metabolism. PMID- 24237390 TI - Hope and the interpersonal-psychological theory of suicidal behavior: replication and extension of prior findings. AB - The interpersonal-psychological theory of suicidal behavior (IPTS; Joiner, 2005) posits that suicidal behavior occurs when an individual has a desire for death (due to the combination of perceived burdensomeness and thwarted belongingness) in addition to an acquired capacity for suicide, which is present when the individual has a low fear of death and high pain tolerance. Previous research has demonstrated an expected negative relation between trait hope and perceived burdensomeness and thwarted belongingness, as well as a more perplexing finding that hope is positively associated with the acquired capability. In a sample of 230 college students, measures of the three components of the IPTS were administered, along with measures of hope, depression, and painful and/or provocative events. Hierarchical regression analyses replicated the previously found associations between hope and burdensomeness and belongingness while controlling for depression and demographic variables. The positive association between hope and acquired capacity was also replicated, but a mediation analysis demonstrated that the effect was statistically accounted for by distress tolerance. The results further support the incremental validity of hope as a consideration in suicide risk assessments and suggest that hope may serve as a protective factor with respect to suicidal desire. PMID- 24237391 TI - A randomised study of a diet intervention to maintain consistent rectal volume for patients receiving radical radiotherapy to the prostate. PMID- 24237392 TI - Multimodal treatment with ALL-like chemotherapy, Auto-SCT and radiotherapy for lymphoblastic lymphoma. AB - BACKGROUND: Recommended treatment for lymphoblastic lymphomas, a highly aggressive, relatively rare lymphoma entity predominantly seen in teenagers and young adults, includes acute lymphoblastic leukemia (ALL)-like induction chemotherapy. Whether these patients should be consolidated with maintenance chemotherapy or autologous stem cell transplantation (Auto-SCT) and the use of radiotherapy are matters of debate. METHODS: We reviewed treatment and outcome for 25 consecutive patients above the age of 15 years with lymphoblastic lymphoma (T-lineage; T-LBL, n = 19; B-lineage; B-LBL, n = 6) seen at a single center during a 12-year period (1999-2011). Patients were given an ALL-like chemotherapy induction regimen, and responding patients were consolidated with Auto-SCT and local radiotherapy when applicable. RESULTS: Median age at diagnosis was 33 years (range 15-65). Seventeen of the T-LBL patients had a mediastinal mass, three patients had central nervous system (CNS) involvement. Chemotherapy with intensified CNS prophylaxis induced an overall response rate of 92% (CR 84%, PR 8%). In total 23/25 (92%) patients underwent Auto-SCT in first remission while 13 of 14 eligible patients with mediastinal involvement received local radiotherapy. Twenty percent of the patients had hepatotoxicity grade 3-4 and 32% thromboembolic events (TE). Two patients (8%) died of treatment-related toxicity. One patient had progressive disease and died of lymphoma. Three patients have relapsed, but two of these (both B-LBL) are currently alive in second CR after Allo-SCT. With a median follow-up of 98 months (range 1-163) the 5- and 8-year PFS and OS are 76% and 84%, respectively. CONCLUSIONS: Combined intensive ALL like induction and early consolidation chemotherapy followed by Auto-SCT and local radiation therapy resulted in high sustained cure rates. PMID- 24237393 TI - 3T MRI improves the detection of transmantle sign in type 2 focal cortical dysplasia. AB - PURPOSE: Type 2 focal cortical dysplasia (FCD2) is one of the main causes of refractory partial epilepsy, but often remains overlooked by MRI. This study aimed to elucidate whether 3T MRI offers better detection and characterization of FCD2 than 1.5T, using similar coils and acquisition time. METHODS: Two independent readers reviewed the 1.5T and 3T MR images of 25 patients with histologically proven FCD2. For both magnetic fields, the ability to detect a lesion was analyzed. We compared the identification of each of the five criteria typical of FCD2 (cortical thickening, blurring, cortical signal changes, subcortical signal changes, and "transmantle" sign) and artifacts, using a four point scale (0-3). Interobserver reliability for lesion detection was calculated. KEY FINDINGS: Seventeen lesions (68%) were detected at 3T, two of which were overlooked at 1.5T. Interobserver reliability was better at 3T (kappa = 1) than at 1.5T (kappa = 0.83). The transmantle sign was more clearly identified at 3T than 1.5T (mean visualization score: 1.72 vs. 0.56; p = 0.002). SIGNIFICANCE: The use of 3T MRI in patients suspected of type 2 FCD improves the detection rate and the lesion characterization owing to the transmantle sign being more clearly seen at 3T. This point is of interest, since this feature is considered as an MR signature of FCD2. PMID- 24237396 TI - Clinical variability and additional mutations in amyotrophic lateral sclerosis patients with p.N352S mutations in TARDBP. PMID- 24237394 TI - Placement of deep brain electrodes in the dog using the Brainsight frameless stereotactic system: a pilot feasibility study. AB - BACKGROUND: Deep brain stimulation (DBS) together with concurrent EEG recording has shown promise in the treatment of epilepsy. A novel device is capable of combining these 2 functions and may prove valuable in the treatment of epilepsy in dogs. However, stereotactic implantation of electrodes in dogs has not yet been evaluated. OBJECTIVE: To evaluate the feasibility and safety of implanting stimulating and recording electrodes in the brain of normal dogs using the Brainsight system and to evaluate the function of a novel DBS and recording device. ANIMALS: Four male intact Greyhounds, confirmed to be normal by clinical and neurologic examinations and hematology and biochemistry testing. METHODS: MRI imaging of the brain was performed after attachment of fiducial markers. MRI scans were used to calculate trajectories for electrode placement in the thalamus and hippocampus, which was performed via burr hole craniotomy. Postoperative CT scanning was performed to evaluate electrode location and accuracy of placement was calculated. Serial neurologic examinations were performed to evaluate neurologic deficits and EEG recordings obtained to evaluate the effects of stimulation. RESULTS: Electrodes were successfully placed in 3 of 4 dogs with a mean accuracy of 4.6 +/- 1.5 mm. EEG recordings showed evoked potentials in response to stimulation with a circadian variation in time-to-maximal amplitude. No neurologic deficits were seen in any dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Stereotactic placement of electrodes is safe and feasible in the dog. The development of a novel device capable of providing simultaneous neurostimulation and EEG recording potentially represents a major advance in the treatment of epilepsy. PMID- 24237397 TI - Mobile health is worth it! Economic benefit and impact on health of a population based mobile screening program in new Mexico. AB - BACKGROUND: HABITS for Life was a 3-year initiative to broadly deliver a statewide biometric and retinal screening program via a mobile unit throughout New Mexico at no charge to participants. The program goal-to identify health risk and improve population health status-was tested over a 3-year period. Value to participants and impact to the healthcare system were measured to quantify impact and value of investing in prevention at the community level. MATERIALS AND METHODS: We used the Mobile Health Map Return-on-Investment Calculator, a mobile screening unit, biometric screening, retinography, and community coordination. Our systems included satellite, DSL, and 3G connectivity, a Tanita(r) (Arlington Heights, IL) automated body mass index-measuring scale, the Cholestec(r) (AlereTM, Waltham, MA) system for biomarkers and glycosylated hemoglobin, a Canon (Melville, NY) CR-1 Mark II camera, and the Picture Archiving Communication System. RESULTS: In this report for the fiscal year 2011 time frame, 6,426 individuals received biometric screening, and 5,219 received retinal screening. A 15:1 return on investment was calculated; this excluded retinal screening for the under-65 year olds, estimated at $10 million in quality-adjusted life years saved. Statistically significant improvement in health status evidenced by sequential screening included a decrease in total cholesterol level (p=0.002) (n=308) and an increase in high-density lipoprotein level after the first and second screening (p=0.02 and p=0.01, respectively), but a decrease in mean random glucose level was not statistically significant (p=0.62). Retinal results indicate 28.4% (n=1,482) with a positive/abnormal finding, of which 1.79% (n=93) required immediate referral for sight-threatening retinopathy and 27% (n=1,389) required follow-up of from 3 months to 1 year. CONCLUSIONS: Screening programs are cost-effective and provide value in preventive health efforts. Broad use of screening programs should be considered in healthcare redesign efforts. Community based screening is an effective strategy to identify health risk, improve access, provide motivation to change health habits, and improve physical status while returning significant value. PMID- 24237398 TI - Development, characterization, and cellular adhesion of poly(L-lactic acid)/poly(caprolactone triol) membranes for potential application in bone tissue regeneration. AB - Poly(L-lactide)/poly(caprolactone triol) (PLLA/PCL-T) membranes were prepared by solution casting in 100/0, 90/10, and 70/30 (w/w) ratios. The membranes were analyzed by dynamic mechanical analysis, differential scanning calorimetry, and mechanical tests. The thermal analysis showed that the 90/10 and 70/30 preparations were partly miscible systems. The glass transition temperature (Tg ) of PLLA decreases as the PCL-T concentration increases, which implies that PCL-T has a plasticizer function. An in vitro study with osteoblastic cells isolated from the calvariae of rats was performed in all preparations. The results obtained in this study showed that the addition of PCL-T to the PLLA matrix modifies its mechanical, thermal, and biological properties. These blends could be useful for tissue engineering for bone applications. PMID- 24237399 TI - Positive selection drives accelerated evolution of mosquito salivary genes associated with blood-feeding. AB - The saliva of bloodsucking animals contains dozens to hundreds of proteins that counteract their hosts' haemostasis, inflammation and immunity. It was previously observed that salivary proteins involved in haematophagy are much more divergent in their primary sequence than those of housekeeping function, when comparisons were made between closely related organisms. While this pattern of evolution could result from relaxed selection or drift, it could alternatively be the result of positive selection driven by the intense pressure of the host immune system. We investigated the polymorphism of five different genes associated with blood-feeding in the mosquito Anopheles gambiae and obtained evidence in four genes for sites with signatures of positive selection. These results add salivary gland genes from bloodsucking arthropods to the small list of genes driven by positive selection. PMID- 24237400 TI - Preparation and characterization of methylene blue nanoparticles for Alzheimer's disease and other tauopathies. AB - Methylene blue (MB) has been shown to slow down the progression of the Alzheimer's disease (AD) and other tauopathies; however distribution of MB into the brain is limited due its high hydrophilicity. In this study, we aimed to prepare novel hydrophobic glutathione coated PLGA nanoparticles to improve bioavailability of MB in the brain. Glutathione coated poly-(lactide-co glycolide) (PLGA-b-PEG) nanoparticles (NPs) were prepared and tested in two different cell culture models of AD expressing microtubule associated protein tau (tau). The NPs showed a particle size averaging 136.5+/-4.4nm, which is suitable for the blood brain barrier (BBB) permeation. The in vitro release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 144 hours. Interestingly, treatment of newly formulated MB-NPs showed a potent reduction in both endogenous and over expressed tau protein levels in human neuroblastoma SHSY-5Y cells expressing endogenous tau and transfected HeLa cells over-expressing tau protein, respectively. Furthermore, in vitro BBB TranswellTM study showed significantly higher permeation of MB-NP compared to the MB solution through the co culture of rat brain endothelial 4 (RBE4) and C6 astrocytoma cells (p<0.05). The proposed MB loaded nanoparticles could provide a more effective treatment option for AD and many other related disorders. PMID- 24237401 TI - CO2 enrichment at treeline: help or hindrance for trees on the edge? PMID- 24237402 TI - Patient engagement: the critical catalyst to health reform in the USA. PMID- 24237404 TI - Cautious optimism regarding the impact of comparative effectiveness research on decision-making. PMID- 24237405 TI - Interview: Health technology assessment in Asia: an emerging trend. AB - Bong-min Yang, PhD (in economics), is Professor and former Dean of the School of Public Health at the Seoul National University, South Korea. Professor Yang has led research and written many papers in health economics and healthcare systems in Korea and Asia. His recent research and publications focus on the field of economic evaluation and outcomes research. He played a key role in the introduction of a formal health technology assessment system within Korean healthcare. He is currently serving as Executive Director, Institute of Health and Environment, Seoul National University. In addition to his research and publications, Professor Yang is Associate Editor for Journal of Comparative Effectiveness Research, is co-editor-in-chief for Value in Health Regional Issues, and is currently chair of the Management Advisory Board of Value in Health and a member of the editorial board of the Journal of Medical Economics. He has been a policy consultant to China, Japan, Indonesia, Hong Kong, Malaysia, Taiwan, Thailand and India. He has also worked as a short-term consultant at the WHO, ADB, UNDP and the World Bank. For the Korean government, he served as Chairperson of the Health Insurance Reform Committee, and Chairperson of the Drug Pricing and Reimbursement Committee. He is currently serving as Chair of the International Society of Pharmacoeconomics and Outcomes Research-Asia Consortium, and a member of the Board of Directors of the International Society of Pharmacoeconomics and Outcomes Research. PMID- 24237403 TI - From efficacy to effectiveness: lessons learned from the Practice-Based Opportunities for Weight Reduction (POWER) trial. PMID- 24237406 TI - Pharmacologic and nonpharmacologic thromboprophylactic strategies in atrial fibrillation. AB - Stroke prevention in atrial fibrillation (SPAF) has traditionally been confined to aspirin and warfarin therapy. Based on CHADS2 scoring it was clearly delineated when aspirin and warfarin would be used in individual patients, but many patients had to forgo recommended therapy due to contraindications or adverse events. There has recently been a paradigm shift in SPAF, with new and promising options on the horizon. These emerging strategies include dual antiplatelet therapy, direct thrombin inhibition, factor Xa inhibition and mechanical prophylaxis therapy. With each of these aforementioned approaches there are moderate to large clinical trials that assess the comparative effectiveness of these approaches in direct comparative trials. From an Ovid MEDLINE search from 1950 to present, we systematically identified 15 randomized trials comparing two thromboprophylactic drugs, devices or procedures for SPAF. Specific mechanical, pharmacologic and pharmacokinetic advantages and disadvantages are also reviewed. PMID- 24237407 TI - A translation table for patient-centered comparative effectiveness research: guidance to improve the value of research for clinical and health policy decision making. AB - This article provides background and context for a series of papers stemming from a collaborative effort by Outcome Sciences, Inc., the National Pharmaceutical Council and the Center for Medical Technology Policy to use a stakeholder-driven process to develop a decision tool to select appropriate methods for comparative effectiveness research. The perceived need and origins of the 'translation table' concept for method selection are described and the legislative history and role of the Patient-Centered Outcomes Research Institute are reviewed. The article concludes by stressing the significance of this effort for future health services and clinical research, and the importance of consulting end-users--patients, providers, payers and policy-makers--in the process of defining research questions and approaches to them. PMID- 24237408 TI - Which design for which question? An exploration toward a translation table for comparative effectiveness research. AB - In this paper, we explore the relative value that different methods offer in answering some stereotypical comparative effectiveness research questions with the goal of informing development of a 'translation table'--a selection tool for choosing appropriate methods for specific comparative effectiveness research questions. This paper was written as a parallel effort to Greenfield and Kaplan (also in this volume) to support the endeavor described in the manuscript by Tunis et al. (also in this volume). Originally based on four cases, the current article has been shortened to two cases for the current discussion. These cases represent research priorities proposed to orient the work of the Patient-Centered Outcomes Research Institute, comparative clinical effectiveness and comparative health services. PMID- 24237410 TI - Comparative effectiveness research: a view from the other side of the pond. PMID- 24237409 TI - Incorporating stakeholder perspectives in developing a translation table framework for comparative effectiveness research. AB - This project used a stakeholder-driven process to understand the factors that drive the selection of study designs for comparative effectiveness research (CER). The project assembled a diverse stakeholder committee to explore the basis of a translation framework and gathered input through surveys, interviews and an in-person meeting. Stakeholders recommended different study designs for the CER topic areas and identified different outcomes as the most important outcomes to study in each area. During the discussions, stakeholders described a variety of factors that influenced their study design recommendations. The stakeholder activities resulted in the identification of several key themes, including the need to have a highly specific detailed research question before discussing appropriate designs and the need to use multiple studies, potentially of different designs, to address the CER topic areas. The insights and themes from this project may inform efforts to develop a translation table. PMID- 24237413 TI - Selective C-2 alkylation of tryptophan by a Pd(II)/norbornene-promoted C-H activation reaction. AB - A palladium(II)-catalyzed norbornene-mediated regioselective alkylation at the C 2 indole position of N-tert-butyloxycarbonyl (Boc)-protected (S)-tryptophan ethyl ester is reported. The protocol employs mild reaction conditions and is tolerant of a range of functional groups. The reaction proceeds without racemization at the stereogenic center of the amino acid. PMID- 24237414 TI - Extragenital subcutaneous cellular angiofibroma of the elbow. PMID- 24237415 TI - N-Heterocyclic carbene-catalyzed cyclotetramerization of acrylates. AB - N-Heterocyclic carbenes (NHCs) were found to catalyze the unprecedented cyclotetramerization of acrylates, producing the trisubstituted cyclopentenones in moderate yields. The proton or deuterium adducts of the deoxy-Breslow intermediate derived from NHC and two molecules of methyl acrylate were obtained. A reaction mechanism involving the new umpolung/cyclization sequence is proposed. PMID- 24237416 TI - Identification of regulated genes conferring resistance to high concentrations of glyphosate in a new strain of Enterobacter. AB - Glyphosate is a widely used herbicide that inhibits 5-enolpyruvylshikimate-3 phosphate synthase (EPSPS) activity. Most plants and microbes are sensitive to glyphosate. However, transgenic-resistant crops that contain a modified epsps obtained from the resistant microbes have been commercially successful and therefore, new resistance genes and their adaptive regulatory mechanisms are of great interest. In this study, a soil-borne, glyphosate-resistant bacterium was selected and identified as Enterobacter. The EPSPS in this strain was found to have been altered to a resistant one. A total of 42 differentially expressed genes (DEGs) in the glyphosate were screened using microarray techniques. Under treatment, argF, sdhA, ivbL, rrfA-H were downregulated, whereas the transcripts of speA, osmY, pflB, ahpC, fusA, deoA, uxaC, rpoD and a few ribosomal protein genes were upregulated. Data were verified by quantitative real-time PCR on selected genes. All transcriptional changes appeared to protect the bacteria from glyphosate and associated osmotic, acidic and oxidative stresses. Many DEGs may have the potential to confer resistance to glyphosate alone, and some may be closely related to the shikimate pathway, reflecting the complex gene interaction network for glyphosate resistance. PMID- 24237417 TI - Counting the cost: estimating the burden of child mental health. AB - The publication of the first report from the Global Burden of Disease (GBD) Study (Murray & Lopez, 1996) radically changed evaluations of the public health significance of mental disorders. Before that time, diseases were typically ranked in terms of their impact on premature mortality. The GBD Study added estimates of impact on disability, and in so doing highlighted the huge public health burden attendant on poor mental health. PMID- 24237418 TI - School exclusion is a mental health issue. PMID- 24237420 TI - Dynamic breathing of CO2 by hydrotalcite. AB - The carbon cycle of carbonate solids (e.g., limestone) involves weathering and metamorphic events, which usually occur over millions of years. Here we show that carbonate anion intercalated layered double hydroxide (LDH), a class of hydrotalcite, undergoes an ultrarapid carbon cycle with uptake of atmospheric CO2 under ambient conditions. The use of (13)C-labeling enabled monitoring by IR spectroscopy of the dynamic exchange between initially intercalated (13)C-labeled carbonate anions and carbonate anions derived from atmospheric CO2. Exchange is promoted by conditions of low humidity with a half-life of exchange of ~24 h. Since hydrotalcite-like clay minerals exist in Nature, our finding implies that the global carbon cycle involving exchange between lithosphere and atmosphere is much more dynamic than previously thought. PMID- 24237419 TI - Copper-transporting ATPase is important for malaria parasite fertility. AB - Homeostasis of the trace element copper is essential to all eukaryotic life. Copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. Here, we describe the functional characterization of an evolutionarily highly conserved, predicted copper-transporting P-type ATPase (CuTP) in the murine malaria model parasite Plasmodium berghei. Live imaging of a parasite line expressing a fluorescently tagged CuTP demonstrated that CuTP is predominantly located in vesicular bodies of the parasite. A P. berghei loss-of-function mutant line was readily obtained and showed no apparent defect in in vivo blood stage growth. Parasite transmission through the mosquito vector was severely affected, but not entirely abolished. We show that male and female gametocytes are abundant in cutp(-) parasites, but activation of male microgametes and exflagellation were strongly impaired. This specific defect could be mimicked by addition of the copper chelator neocuproine to wild-type gametocytes. A cross-fertilization assay demonstrated that female fertility was also severely abrogated. In conclusion, we provide experimental genetic and pharmacological evidence that a healthy copper homeostasis is critical to malaria parasite fertility of both genders of gametocyte and, hence, to transmission to the mosquito vector. PMID- 24237421 TI - The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6. AB - We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, this study highlights the first native bacterial production of isopterocarpolone and the first full characterisation of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery. PMID- 24237423 TI - The absence of a metal-on-metal bearing does not preclude the formation of a destructive pseudotumor in the hip--a case report. PMID- 24237422 TI - Different diagnostic properties of C-reactive protein, real-time PCR, and histopathology of frozen and permanent sections in diagnosis of periprosthetic joint infection. AB - BACKGROUND AND PURPOSE: There are several diagnostic tests for periprosthetic joint infection (PJI). We evaluated the properties of preoperative serum C reactive protein (CRP), real-time polymerase chain reaction (PCR), and histopathological evaluation of frozen and permanent sections in clinical cases with culture-positive PJI. PATIENTS AND METHODS: 63 joints involving 86 operations were analyzed using serum CRP measurement prior to operation and tissue samples were collected intraoperatively for real-time PCR and histopathology. We calculated the sensitivity, specificity, likelihood ratio of positive test results (PLR), and likelihood ratio of negative test results (NLR) for each test in relation to positive microbiological culture results as the gold standard. RESULTS: The sensitivity and specificity of diagnosis with serum CRP were 90% and 85%, respectively. The corresponding values for real-time PCR and histopathology of frozen and paraffin tissue sections were 90% and 45%, 71% and 89%, and 90% and 87%, respectively. Serum CRP had a PLR of 5.8 and an NLR of 0.12, and real-time PCR had a PLR of 1.6 and an NLR of 0.18. The corresponding figures for frozen tissue sections were 6.6 and 0.32, and those for paraffin sections were 7.1 and 0.11, respectively. INTERPRETATION: The results suggest that real-time PCR and histopathology of frozen sections is a good combination. The former is suitable for screening, with its high sensitivity and good NLR, while the latter is suitable for definitive diagnosis of infection, with its excellent specificity and good PLR. PMID- 24237424 TI - Monoblock all-polyethylene tibial components have a lower risk of early revision than metal-backed modular components. AB - BACKGROUND AND PURPOSE: With younger patients seeking reconstructions and the activity-based demands placed on the arthroplasty construct, consideration of the role that implant characteristics play in arthroplasty longevity is warranted. We therefore evaluated the risk of early revision for a monoblock all-polyethylene tibial component compared to a metal-backed modular tibial construct with the same articular geometry in a sample of total knee arthroplasties (TKAs). We evaluated risk of revision in younger patients (< 65 years old) and in older patients (>= 65 years old). METHOD: Fixed primary TKAs with implants from a single manufacturer, performed between April 2001 and December 2010, were analyzed retrospectively. Patient characteristics, surgeon, hospital, procedure, and implant characteristics were compared according to tibial component type (monoblock all-polyethylene vs. metal-backed modular). All-cause revisions and aseptic revisions were evaluated. We used descriptive statistics and Cox regression models. RESULTS: 27,657 TKAs were identified, 2,306 (8%) with monoblock and 25,351 (92%) with modular components. In adjusted models, the risk of early all-cause revision (hazard ratio (HR) = 0.5, 95% confidence interval (CI): 0.3-0.8) and aseptic revision (HR = 0.6, CI: 0.3-1.2) was lower for the monoblock cohort than for the modular cohort. In older patients, the early risk of all-cause revision was 0.6 (CI: 0.4-1.0) for the monoblock cohort compared to the modular cohort. In younger patients, the adjusted risk of all-cause revision (HR = 0.3, CI: 0.1-0.7) and of aseptic revision (HR = 0.3, CI: 0.1-0.7) were lower for the monoblock cohort than for the modular cohort. INTERPRETATION: Overall, monoblock tibial constructs had a 49% lower early risk of all-cause revision and a 41% lower risk of aseptic revision than modular constructs. In younger patients with monoblock components, the early risk of revision for any cause was even lower. PMID- 24237425 TI - Toll-like receptors in human chondrocytes and osteoarthritic cartilage. AB - BACKGROUND AND PURPOSE: Degenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes. METHODS: We studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different OARSI grades. Effects of a danger signal and of a pro-inflammatory cytokine on TLRs were also studied. RESULTS: In primary 2D-chondrocytes, TLR1 and TLR2 were strongly expressed. Stimulation of 2D and 3D chondrocytes with a TLR1/2 specific danger signal increased expression of TLR1 mRNA 1.3- to 1.8-fold, TLR2 mRNA 2.6- to 2.8-fold, and TNF-alpha mRNA 4.5- to 9-fold. On the other hand, TNF alpha increased TLR1 mRNA] expression 16-fold, TLR2 mRNA expression 143- to 201 fold, and TNF-alpha mRNA expression 131- to 265-fold. TLR4 and TLR9 mRNA expression was not upregulated. There was a correlation between worsening of OA and increased TLR immunostaining in the superficial and middle cartilage zones, while chondrocytes assumed a CD166(*) progenitor phenotype. Correspondingly, TLR expression was high soon after differentiation of mesenchymal stem cells to chondrocytes. With maturation, it declined (TLR2, TLR9). INTERPRETATION: Mature chondrocytes express TLR1 and TLR2 and may react to cartilage matrix/chondrocyte derived danger signals or degradation products. This leads to synthesis of pro inflammatory cytokines, which stimulate further TLR and cytokine expression, establishing a vicious circle. This suggests that OA can act as an autoinflammatory disease and links the old mechanical wear-and-tear concept with modern biochemical views of OA. These findings suggest that the chondrocyte itself is the earliest and most important inflammatory cell in OA. PMID- 24237426 TI - [t030 is the most common spa type among methicillin-resistant Staphylococcus aureus strains isolated from Turkish hospitals]. AB - Staphylococcus aureus is one of the most frequent agents causing hospital infections. S.aureus has a great ability to adapt itself to variety of conditions and successful clones can be epidemic and even pandemic by its ability spread from one continent to another. The aims of this study were to detect spa types of 397 methicillin-resistant S.aureus (MRSA) strains isolated from 12 centers in different geographical regions of Turkey from 2006 to 2008, and to investigate their clonality by PFGE and MLST typing. Additionally, 91 MRSA from four of those 12 centers isolated during 2011 were also studied for their spa types. PFGE profiles indicated the presence of a major pulsotype, namely pulsotype A with a rate of 91.4% (363/397), followed by pulsotype B (n= 18, 4.5%) and pulsotype C (n= 11, 2.8%). Among isolates tested 363 (91.4%) were SCCmec type III, 30 (7.6%) were SCCmec type IV. Sequence analysis of representative isolates revealed that ST239 (85.1%) was the most common MLST type followed by two MLST types ST737 (4%), and ST97 (2.8%), both SCCmec type IV. Two isolates were ST80 with SCCmec type IV. Of 397 isolates, 338 (85.1%) were t030, followed by t005 (2.5%) and t632 (2%). Among MRSA isolated during 2011, 64 (70.3%) of 91 were t030, 4 (4.4%) were t005, 2 (2.2%) were t015, and 2 (2.2%) were t1094. Among centers the t030 prevalence of 2006-2008 isolates ranged from 59-100%. The highest t030 prevalence was found in Ankara (100%) and lowest in Trabzon (59%) provinces which are located at central and northestern Anatolia, respectively. In Istanbul province, the prevalence of t030 was 94.5% among 2006-2008 isolates which decreased to 55.5% among 2011 isolates. Also a decrease in t030 rates was observed among samples from Konya and Trabzon but not from Aydin. Our results showed that the most common MRSA clone in Turkey is ST 239-SCCmec type III, t030 which persisted during the six years of the study period. Presence of PVL toxin gene was tested by PCR and 5 (3%) isolates found to be positive, of them two were SCCmec Type IV ST80 and three were SCCmec Type III-ST239. This study is the largest epidemiological survey ever done in Turkey which showed presence of a hospital Turkish clone TR09 (ST239-SCCmecIII-t030) and a community clone TR10 (ST737 SCCmecIV-t005) largely disseminated in Turkey. PMID- 24237427 TI - [Investigation of plasmid mediated AmpC beta-lactamases among Escherichia coli and Klebsiella pneumoniae isolated from blood cultures]. AB - The aim of this study was to investigate the prevalence and types of plasmid mediated AmpC (pAmpC) beta-lactamase enzymes in Escherichia coli and Klebsiella pneumoniae strains isolated from blood cultures of hospitalized patients in Dokuz Eylul University Hospital between 2007 and 2012. A total of 261 isolates which consisted of 184 E.coli (70.5%) and 77 K.pneumoniae (29.5%) were included in the study. All isolates were resistant to cefotaxime and/or ceftazidime but susceptible to imipenem. Cefoxitin resistance was investigated as an indicator of AmpC type enzymes. A total of 57 (21.8%) isolates which were cefoxitin-resistant (32 E.coli, 25 K.pneumoniae), were screened for pampC genes by a multiplex polymerase chain reaction (PCR) assay. Additionally, 10 of each cefoxitin susceptible isolates per year were chosen randomly and screened by the same PCR assay to detect the presence of ACC enzymes, which can not hydrolyze cefoxitin. Positive PCR results were confirmed by sequence analysis. Plasmid analysis and macrorestriction analysis were performed for pampC-positive isolates. The presence of pAmpC enzymes has been shown in 9.4% (3/32) of cefoxitin-resistant E.coli, and 8% (2/25) of cefoxitin-resistant K.pneumoniae strains. It was noted that there were no strains producing this enzyme isolated in 2007 and 2008, however the prevalence of pAmpC was detected as 1.6% in 2009 (one ACT-1 producing K.pneumoniae), increasing to 4.8% in 2011 (one ACT-1 producing K.pneumoniae) and 6.4% in 2012 (three CMY-2 producing E.coli). These enzymes were found to be carried on 81 kb size plasmids in K.pneumoniae isolates and on a 9 kb size plasmid in E.coli isolates. Macrorestriction analysis indicated that two of the three CMY-2 producing E.coli had the same PFGE (Pulsed-field gel electrophoresis) pattern. If these two strains are considered as identical, it can be concluded that the prevalence of pAmpC was low in the strains isolated between 2007-2012 (4/261; 1.5%) in our institution. On the other hand, the increasing prevalence of pAmpC in 2011 and 2012 should be considered as a warning for the implementation of infection control measures and monitorization of the prevalence in order to prevent the dissemination of pAmpC. As far as the current literature is concerned, this is the first study that demonstrated the presence of the ACT-1 enzyme in K.pneumoniae isolates in Turkey. PMID- 24237428 TI - [Distribution of blaOXA genes in Acinetobacter baumannii strains: a multicenter study]. AB - Acinetobacter baumannii is the most important agent of nosocomial infections within the Acinetobacter genus. This gram-negative coccobacillus is intrinsically resistant to many antibiotics used in antimicrobial therapy, and capable of developing resistance including carbapenems. The objective of this study was to develop a multiplex real time polymerase chain reaction (qPCR) kit for OXA subgroups in A.baumannii, and to investigate the distribution of OXA subgroups in A.baumannii strains isolated from geographically different regions of Turkey. A total of 834 A.baumannii clinical isolates collected from different state and university medical centers in 13 provinces (Afyonkarahisar, Ankara, Bolu, Elazig, Erzurum, Isparta, Istanbul, Kahramanmaras, Konya, Sakarya, Van) between 2008 2011, were included in the study. The isolates were identified by conventional methods and automated systems [Vitek2 (bioMerieux, ABD) and Phoenix (BD Diagnostic, MD)]. The susceptibility profiles of the isolates were studied with automated systems and standard disc diffusion method. All samples were subjected to qPCR to detect blaOXA-51-like, blaOXA-23-like and blaOXA-58-like genes. A conventional PCR method was also used to detect blaOXA-24-like gene. The resistance rates observed during the study period were as follows: 96.8% for amoxicillin-clavulanate, 86.8% for ciprofloxacin, 74.7% for gentamicin, 71.7% for amikacin, 73.5% for cefaperozone-sulbactam, 72.1% for imipenem and 73% for meropenem. Six hundred and two (72.2 %) isolates were resistant to both imipenem and meropenem. Colistin was found to be the most effective antibiotic against A.baumannii isolates with 100% susceptibility rate. All isolates were positive for blaOXA-51-like, however blaOXA-24-like gene could not be demonstrated in any isolate. Total positivity rates of blaOXA-23-like and blaOXA-58-like genes were found as 53.7% and 12.5%, respectively, while these rates were 74.4% and 17.3% in carbapenem-resistant isolates, respectively. Twenty-five isolates were positive for both blaOXA-23-like and blaOXA-58-like genes. All of the carbapenem-resistant isolates have OXA type genes with the exception of blaOXA-24-like gene. The positivity rates for blaOXA-23-like and blaOXA-58-like genes varied for each center. In addition, there was a decrease in the frequency of blaOXA-58-like gene, however both blaOXA-23-like gene and carbapenem resistance rates increased during the study period. In conclusion, high rates of resistance to carbapenems were also remarkable but A.baumannii strains keep on sensitivity to colistin. Both blaOXA-23-like and blaOXA-58-like genes were shown to be widespread in carbapenem-resistant A.baumannii clinical isolates. However, blaOXA-23-like gene positive strains were increased throughout the study. Currently, multiplex qPCR is the best way for rapid diagnosis of resistant bacteria for prevention of hospital-acquired infections. The multiplex qPCR kit developed in this study could be useful for rapid diagnosis and identify the frequencies of blaOXA-23 like, blaOXA-51-like and blaOXA-58-like genes in carbapenem-resistant A.baumannii clinical isolates. PMID- 24237429 TI - [Antibiotic resistance patterns of Escherichia coli strains isolated from urine cultures in Turkey: a meta-analysis]. AB - Escherichia coli is the most frequently isolated microorganism from both community-acquired and nosocomial urinary tract infections in Turkey. A large number of studies concerning antibiotic susceptibility of E.coli have been published from different centers throughout the country. The aim of this study was to evaluate the antibiotic resistance patterns of E.coli strains isolated from urine cultures by a meta-analysis in published medical literature between the years of 1996-2012 in Turkey. The study was planned and conducted in accordance with the declaration of PRISMA and describes the methods of literature search, the determining criteria for inclusion and evaluation of articles, data collection and statistical analysis. To find the published series Google Scholar and PubMed international databases were used to access published manuscripts evaluated according to the determined criteria for acceptance and rejection. For each study, general data and antibiotic resistance rates were collected as a common unit. Publications considered as lacking in appropriate content was eliminated from the study. Statistical analysis of the data obtained were 95% confidence intervals, and p<= 0.05 value was considered as significant difference. A total of 228 articles were found to be published during 1996-2012 period, while 101 of them were included in the meta-analysis according to the eligibility criteria. The analyses indicated that nitrofurantoin and piperacillin resistance rates have been decreased, whereas ciprofloxacin, cefepime, co trimoxazole and extended-spectrum beta-lactamase (ESBL) positivity rates have been increased during the study period. The increases in the rates of ciprofloxacin and cefepime resistance and and ESBL production were statistically significant (p< 0.05). A significant reduction in resistance rates for ampicilin, amoxicillin-clavulanate, and amikacin was noted in pediatric patients between 2002-2012. Ceftriaxone, imipenem, gentamicin and amikacin resistance were not homogenous between the geographical regions, and statistically significant differences were observed for amoxicillin-clavulanate, cefuroxime and ciprofloxacin resistance rates (p< 0.05). Antibiotic resistance rates, except for imipenem, in bacterial strains, isolated from hospitalized patients were found significantly higher in strains obtained from outpatients. The differences between those groups were significant in terms of ampicilin, amoxicillin clavulanate, cefuroxime, ceftriaxone, trimethoprim-sulfamethoxazole, gentamicin, ciprofloxacin, amikacin and cefepime resistances (p< 0.05). It has been noted that antibiotic resistance patterns of E.coli strains isolated from urine cultures between 1996-2012 demonstrated significant variability, and many studies were based only on laboratory data. The results of this meta-analysis demonstrated that the resistance rates in commonly-used antibiotics for empirical therapy were high. In conclusion, information obtained by systematic evaluation of national data will be valuable for the determination of optimal antibiotic regimens and in prevention of unnecessary antibiotic use. PMID- 24237430 TI - [Evaluation of a hospital outbreak related to carbapenem-resistant Pseudomonas aeruginosa]. AB - Pseudomonas aeruginosa is an important nosocomial pathogen that causes opportunistic infections and hospital outbreaks. During October 2012, carbapenem resistant P.aeruginosa strains with similar antibiotic resistance patterns, were isolated from specimens sent from the intensive care and plastic surgery units in our hospital. Thus a hospital outbreak was suspected. The microbiology laboratory database was retrospectively searched and all strains of P.aeruginosa isolated during the four month period, starting with the initial carbapenem-resistant strain in August 2012, was evaluated as a hospital outbreak. The aim of this study was to define the outbreak by investigating the clonal relationship between the strains, to detect the potential environmental sources and to evaluate the period of the outbreak, risk factors and the efficiency of infection control measures. The study was conducted between August-November 2012. Twenty patients with carbapenem-resistant P.aeruginosa (CRPA) positive cultures were included in the study. The control group consisted of 22 patients with carbapenem-susceptible P.aeruginosa (CSPA) positive cultures. The clonal relationship between 26 CRPA strains was studied by pulsed-field gel electrophoresis (PFGE). The PFGE results indicated that CRPA strains in our hospital were not related to a single clone, however, there were four major clones composed of four to eight strains. Logistic regression analysis indicated that the risk increased 15.7 fold (95% CI: 1.19 207.76) by the use of carbapenem, 76.8 fold (95% CI: 2.03-2901.30) by surgical procedures and 0.787 fold (95% CI: 0.63-0.97) by the duration of hospital stay. Surveillance cultures from health-care personel and the environment performed in course of the outbreak, yielded no growth of a strain with the similar antibiotic resistance pattern. The spread of CRPA has been controlled by the use of effective precautionary measures, regressing the isolate number to 0-1 strain/month. Since CRPA infections have high mortality and lack therapeutic alternatives, they should be regarded among the priorities of the infection control programmes. This study has enabled to test the effectiveness of the infection control program, to make plans for the possible future outbreaks and to train the staff. PMID- 24237431 TI - [Investigation of baseline antiviral resistance in treatment-naive chronic hepatitis B cases]. AB - Naturally-occurring mutations associated with resistance to nucleoside/nucleotide analogues (NA) can be detected in a group of treatment-naive individuals chronically infected with hepatitis B virus (HBV). Genotypic resistance testing prior to the initiation of NA therapy may facilitate the selection of optimal drug regime and help to prevent early emergence of clinical resistance. In this study, presence of resistance mutations in treatment-naive individuals with chronic hepatitis B (CHB) was investigated in Hacettepe University Hospital, a referral center in Ankara province, Turkey. A total of 42 patients (17 female, 25 male; age range: 18-62 years) diagnosed as CHB were enrolled in the study with informed consent. All of the patients were negative for hepatitis C and D viruses and human immunodeficiency virus coinfections, and none had a history of interferon or NA treatment. HBV viral load, HBV markers and hepatic enzymes in patients were determined via standardized commercial assays. For the detection of NA resistance mutations, a partial sequence of approximately 250 nucleotides, harboring the frequently-observed sites for NA resistance was amplified via nested PCR and characterized by direct sequencing of the amplicons. The sequences were handled and interpreted for the presence of mutations via various softwares and a web-based virtual phenotyping tool. Well-characterized sequences were obtained in 30 out of 42 samples (71.4%). All circulating HBV strains were observed as genotype D. Nucleotide variations were detected in 19 individuals (63.5%) that comprise silent mutations without amino acid substitution in 8 (26.6%), mutations with undetermined significance in 7 (23.3%) and mutations associated with NA resistance in 3 (10%) patients. Mutations conferring resistance to entecavir + lamivudine (S202G, M204V, L180M, T184N) were identified in one patient whereas L180P, A181Q and A194V substitutions associated with probable lamivudin + adefovir and tenofovir resistance, respectively, were detected in other patients. All patients with resistance mutations were HBsAg and HBeAg positive, anti-HBe negative and had viral loads exceeding 3 x 10(7) IU/ml. In two patients, the route for HBV transmission was vertical. Since no follow-up samples were available from individuals with resistance mutations, alterations in serological markers, viral load and mutation patterns could not be monitored. In conclusion, the presence of NA resistance mutations were revealed in treatment naive CHB cases in a referral hospital in Turkey. The impact and cost-effectivity of detecting naturally-occurring resistance mutations for clinical follow-up prior to the antiviral therapy need to be elucidated by prospective studies. PMID- 24237432 TI - [Investigation of the presence of human metapneumovirus in patients with chronic obstructive pulmonary disease and asthma and its relationship with the attacks]. AB - Human metapneumovirus (hMPV), an enveloped RNA virus classified in Paramyxoviridae family, was first characterized in 2001 from children with acute respiratory tract infection. Recent studies have suggested hMPV to play a role in chronic obstructive pulmonary disease (COPD) and asthma attacks. The aims of this study were to investigate the frequency of hMPV in patients with COPD and asthma, its effects on the severity of the attacks and the relationship between demographical and clinical factors. A total of 123 patients, including 66 with COPD (45 were in attack and 21 were stable) and 57 with asthma (33 were in attack and 24 were under control) diagnosed according to the criteria of Global Initiative for Chronic Obstructive Lung Disease and the Global Strategy for Asthma Management and Prevention, respectively, were included in the study. Nasopharyngeal lavage samples collected from all of the patients have been evaluated for the presence of hMPV-RNA by using a reverse transcriptase polymerase chain reaction (RT-PCR) targeting F gene region of the virus. hMPV-RNA positivity rates in patients with COPD and asthma were observed as 30.3% (20/66) and 31.6% (18/57), respectively, and the difference between the groups were not statistically significant (p= 1.00). When patients were compared according to their disease status, hMPV was detected in 31.1% (14/45) of patients with COPD attack and 28.6% of stable patients (p> 0.05). These rates were found as 36.4% (12/33) and 25% (6/24) in patients with asthma attack and controlled asthma, respectively (p> 0.05). Although the virus detection rates in patients with COPD and asthma attacks (26/78; 33.3%) were higher than the patients with stable/controlled disease (12/45; 26.7%), the difference was not found as statistically significant (p= 0.57). The detection rate of hMPV-RNA was 26.1% in patients who can be treated at home and hospital without any need of intensive care and mechanical ventilation, while this rate was 36.4% in patients with COPD attack who require intensive care and mechanical ventilation (p= 0.67). Similarly, hMPV-RNA was detected more frequently in asthma patients with moderate and severe attacks (45%) than in patients with mild attacks (23.1%); however this difference was also not statistically significant (p= 0.28). No association of hMPV-RNA detection and demographical and clinical characteristics (age, gender, medical history, smoking status, allergy, COPD severity, asthma severity, the severity of attacks, using inhaled steroid, fever) of the patients could be demonstrated (p> 0.05), except the severity of the disease in patients with asthma (p= 0.02). In conclusion, further studies with large number of cases are needed to elucidate the role of hMPV in the occurrence and severity of COPD and asthma attacks. PMID- 24237433 TI - [Determination of hepatitis C virus genotypes among hepatitis C patients in Eastern Black Sea Region, Turkey]. AB - Hepatitis C virus (HCV), the major cause of transfusion-associated hepatitis, is an important public health problem in the world as well as in Turkey. HCV is grouped as six distinct genotypes and a large number of closely-related subtypes. Genotyping of HCV is an important tool for providing epidemiological data, prediction of prognosis, and optimization of antiviral therapy. This study was carried out to determine the distribution of HCV genotypes in hepatitis C patients residing in different provinces of the Eastern Black Sea Region, Turkey. A total of 304 HCV-RNA positive cases (151 male, 153 female; age range: 11-93 years, mean age: 55.2 +/- 13.3 years) who were admitted to the Molecular Microbiology Unit of Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, between January 2009 to December 2012, were included in the study. HCV genotypes were detected in plasma samples of the patients by using commercial assays [INNO-LiPA HCV II (Innogenetics, Belgium) or Abbott RealTime HCV Genotype II (Abbott Molecular Inc, USA)]. Due to the ambiguous genotyping results in some samples with these methods, an in-house multiplex polymerase chain reaction (PCR) assay with genotype-specific primers was also used in the study. Similar to the previous reports from Turkey, our results showed that four HCV genotypes (1, 2, 3, and 4) prevailed in the Eastern Black Sea Region and the predominant genotype and subtype were genotype 1 (92.8%) and 1b (87.5%), respectively. Distribution of genotypes were observed to vary according to the province. Prevalences of subtype 1a, genotype 2, 3, and 4 were noted as 5.3%, 1.6%, 4.9%, and 0.7%, respectively. Furthermore, the samples from Giresun, Gumushane and Bayburt provinces, which are relatively less immigrated, had higher genotype 1, and the prevalence rates in the region was affected by the presence of non-citizen residents. This study is the first report on distribution of HCV genotypes in chronic hepatitis C patients living in the provinces of Eastern Black Sea Region. Moreover, genotype-specific multiplex PCR assay could be useful in resolving certain methodological problems such as "ghost bands" encountered in line probe assay (LiPA) and multiple genotypes (including genotype 4) observed in real-time PCR during the characterization of HCV genotypes seen in Turkey. PMID- 24237434 TI - [Investigation of Pneumocystis jirovecii in clinical specimens by different methods]. AB - Pneumocystis jirovecii causes pneumonia in premature, newborn or malnourished children, as well as in immunocompromised subjects such as chemotherapy receiving, transplant and AIDS patients. Since the mortality and morbidity rates of Pneumocystis pneumonia (PCP) in these patients were high, rapid and accurate diagnosis is important. The aim of this study was to evaluate the diagnostic value of Giemsa staining (GS), direct fluorescent antibody (DFA) assay, (1->3) beta-D-Glucan (BDG) test and real-time polymerase chain reaction (PCR) for the detection of P.jirovecii in clinical specimens. A total of 100 PCP-suspected patients with underlying diseases who were followed-up in outpatient and inpatient clinics of our hospital between December 2008-July 2010 were included in the study. All the patients (66 male, 34 female; mean age: 42.04 years) were under long-term immunosuppressive drug therapy due to their hematological malignancies, kidney transplantation, neutropenia or chronic diseases. Respiratory samples [86 bronchoalveolar lavage (BAL), 8 endotracheal aspirate, 1 nasotracheal aspirate, 3 pleural, 2 lung biopsy samples] obtained from the patients have been studied with GS (Merck, Germany), DFA (Pneumo Cel, Cellabs, Australia) and PCR (primers targeting MSG gene, LightCycler, Roche, USA), while serum samples (n= 100) with BDG (Fungitell, ACC Inc, USA) and PCR methods. In BAL samples two were found positive by GS, DFA and PCR, and six were positive only by PCR, yielding a total positivity in 8 (8%) samples. All of the sera were negative with PCR, however 29 of them were positive (> 80 pg/ml), five were equivocal (61 79 pg/ml) and 66 were negative (< 60 pg/ml) with BDG test. Eight patients with positive results in BAL-PCR were also positive with BDG test. Although the agreement between GS and DFA was high (kappa= 1), it was observed as low between PCR and DFA (kappa= 0.38), DFA and BDG (kappa= 0.07), BAL-PCR and BDG (kappa= 0.28). DFA taken as the gold standard, the sensitivity and specificity values of GS, PCR and BDG methods were calculated as 100% and 100%; 100% and 93%; 100% and 67%, respectively. In the ROC analysis performed for BDG test, with DFA and BAL PCR taken as the gold standards, the sensitivity, specificity and cut-off values of BDG were estimated as 100%, 93.9% and 494 pg/ml, and 100%, 72.8% and 62 pg/ml, respectively. Our data indicated that, overall specificity was high (100%) when using GS and DFA tests together, while the sensitivity has been elevated to 93% with the additional use of PCR and BDG tests, in the diagnosis of PCP-suspected patients. In conclusion, combination of all these tests should be performed for the laboratory diagnosis of P.jirovecii. PMID- 24237435 TI - [Evaluation of imported Plasmodium falciparum malaria cases: the use of polymerase chain reaction in diagnosis]. AB - Malaria affecting almost half of the world population continues to be an important health problem. Although domestic malaria cases have been decreasing in Turkey recently, cases caused by Plasmodium falciparum have increased due to the frequent travelling to Africa. The aims of this study were to evaluate demographic characteristics, clinical and laboratory findings in cases with falciparum malaria who attended to our clinic in 2012-2013 period, and the impact of polymerase chain reaction (PCR) for diagnosis. Nine patients evaluated were all male with a mean age of 34.3 (age range: 18-48) years, with the history of travel to Africa. Six cases did not take prophylaxis against malaria and other three cases used insufficient time. Mean duration of symptoms after return was 18.4 (range: 1-75) days, and the patients were admitted to the clinic within a mean of 5.2 (range: 1-15) days. Two patients had leucopenia, two patients had anemia, and eight patients had thrombocytopenia on admission. Alanine aminotransferase (ALT) levels in four cases and total bilirubin levels of six cases were over upper normal limits. Definitive diagnosis of cases was performed with the detection of ring and/or gametocytes forms of the parasite in Giemsa stained peripheral blood smears. Furthermore, samples from seven patients were studied by nested PCR by using genus (Plasmodium rPLU 1 and 5) and species (rFAL 1 and 2, rVIV 1 and 2, rMAL 1 and 2, rOVA 1 and 2) specific primers. All of these seven samples yielded positive results with primers specific for P.falciparum ssrRNA. In the treatment, arthemeter/lumefantrin and doxycycline combination was used in seven patients, while intravenous artesunate and doxycycline combination was given to two patients, resulting with complete cure. Mean duration for the resolving of fever was 3.3 days, and mean duration for clearing the parasitemia from peripheral blood was 4.9 days. Initial ALT values and the duration of fever resolution (-796; p= 0.010), as well as the duration of parasitemia and initial thrombocyte counts (-797; p= 0.010) were negatively- correlated. It was concluded that, providing sufficient information on malaria and prophylaxis to people travelling to the endemic areas are crutial for protection. Moreover, in endemic areas for Crimean-Congo hemorrhagic fever, patients with fever and thrombocytopenia should be questioned in detail about the travel history, and peripheral blood smears should be examined in terms of malaria, since their clinical features are similar. Plasmodium PCR should be considered as one of the alternative diagnostic method in malaria, especially in cases with inconclusive microscopy. PMID- 24237436 TI - [In vitro activity of ceftaroline to MRSA isolates: a multicenter study]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that cause severe community- and hospital-acquired infections. Studies continue on searching alternatives due to the limited number of therapeutic options in MRSA infections. Ceftaroline is a wide-spectrum new generation cephalosporin which has been begun to be used in treatment of skin and respiratory tract infections caused by MRSA. The aim of this study was to investigate the in vitro activity of ceftaroline against MRSA strains isolated from various clinical specimens in microbiology laboratories of seven hospitals located at different provinces (Bolu, Samsun, Rize, Tekirdag, Sakarya, Amasya, Osmaniye) of Turkey. A total of 192 MRSA isolates (89 skin/wound/abscess, 38 blood, 36 respiratory tract, 29 urine/sterile body fluids/catheter) were included in the study, and ceftaroline susceptibilities of the strains were detected by broth microdilution method. MIC values of 181 (94.3%) isolates were determined as <= 1 ug/ml meaning of susceptible according to the criteria of CLSI, and MIC values of 11 (5.7%) isolates were found as 2 ug/mL indicating intermediate susceptibility. The range of MIC values of the isolates was found between 0.25-2 ug/ml. The rates of intermediate isolates have varied between 0-12.5% from the participating centers. MIC50 and MIC90 values of all the isolates were determined as 0.5 ug/ml and 1 ug/ml, respectively. No significant differences were found between the centers in terms of mean MIC values (p> 0.05). MIC50 and MIC90 values in Samsun and Bolu isolates were found to be the same with the whole group, however, MIC50 and MIC90 were 0.5 ug/ml and 0.5 ug/ml in Amasya isolates and 1 ug/ml and 1 ug/ml in Rize, Tekirdag, Osmaniye and Sakarya isolates, respectively. When evaluating MIC50 and MIC90 values and isolation rates of intermediate strains according to the specimen types, there were no significant differences (p> 0.05). Susceptibility rates to ceftaroline and the distribution profiles of MIC values of the isolates obtained from seven centers of Turkey have been detected similar with the previous American and European reports. With this study, initial data on the activity of ceftaroline against MRSA were obtained from Turkey. These preliminary findings indicate that ceftaroline is effective even on Turkish isolates and can be a suitable treatment in cases requiring wide-spectrum antimicrobiotic use, however further large-scaled studies are needed. PMID- 24237437 TI - [Serotype distribution and antibiotic susceptibilities of Streptococcus pneumoniae causing acute exacerbations and pneumonia in children with chronic respiratory diseases]. AB - This study aimed to investigate serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates obtained from children with chronic respiratory diseases admitted to hospital with a diagnosis of acute exacerbations between 2008-2010 at Marmara University Hospital, Istanbul, Turkey. Sixty one S.pneumoniae strains isolated from the respiratory samples of patients were studied for erythromycin, clindamycin, tetracyline, trimethoprim sulphametoxazole (TMP-SMX), vancomycin, levofloxacin susceptibilities by disk diffusion method; MIC values of penicillin and ceftriaxone were determined by E test (AB Biodisk, Sweden). Results were evaluated according to the CLSI standards. The erythromycin-clindamycin double disc method was applied for the detection of macrolide resistance phenotypes. The presence of macrolide resistance genes, ermB, mef(A)/(E), ermTR were determined by PCR using specific primers for each gene. The serotypes were determined by multiplex PCR using specific primers for 40 different serotypes. According to CLSI criteria, penicillin resistance in S.pneumoniae isolates were found to be 8.2% (5/61) and intermediate resistance rate was 54% (33/61) for oral penicillin. Penicillin resistance were found to be only 1.6% (1/61) for parenteral penicillin. Resistance rates of erythromycin, clindamycin, tetracyline, TMP-SMX were detected as 55.8%, 46%, 47.5% and 67.2%; respectively. No resistance was detected to vancomycin and levofloxacin. Constitutive macrolide-lincosamide-streptogramin B (cMLSB) phenotype and M phenotype were observed in 82.4% (n= 28) and 17.6% (n= 6) of the macrolide resistant isolates, respectively. Inducible macrolide lincosamide-streptogramin B (iMLSB) phenotype was not detected. The macrolid resistance genotypes, ermB, mef(A)/(E), were positive 50% and 14.7%; respectively. Both ermB and mef(A)/(E) genes were detected 35.3% of the macrolid resistant isolates. None of the isolates were positive for ermTR gene. The most common S.pneumoniae serotypes were determined as serotype 19F, 23F and 6, furthermore penicillin (34%, 15.7% and 18.4%, respectively) and macrolide (38.2%, 20.6% and 14.7%, respectively) resistance rates of those serotypes were found relatively high. Serotype covarage of 7-, 10-, 13-valent conjugated pneumococcal vaccines and 23-valent pneumococcal vaccine were 65%, 67%, 69%, and 78.6%, respectively. In our country, use of the vaccines with these coverage rates has been observed to be effective in children exposed to intensive use of antibiotics with chronic lung disease. PMID- 24237438 TI - [Determination of Salmonella serotypes by conventional and molecular methods]. AB - Determination of Salmonella enterica serotypes is crucial for epidemiological studies. Salmonella serotypes are defined on the basis of somatic (O) and flagellar (H) antigens, both of which are present in the cell wall of Salmonella. The aim of this study was to compare the results of molecular serotyping obtained by multiplex polymerase chain reaction (mPCR) with conventional serotyping results. Conventional serotyping has been performed in Ministry of Health Refik Saydam Hygiene Center as part of the National Laboratory of Enteric Pathogenes Surveillance Network (UEPLA). A total of 100 Salmonella strains, thay comprise 14 different serotypes by the reference laboratory have been investigated by using specific primers for Salmonella serogroups (A, B, C1, D and E) and Vi antigen gene clusters via mPCR method. Serotypes have been determined by applying four sequential mPCR targeting the fliC and fliB genes encoding the H1 antigens (H1: a, -b, -d, -g,m, -i, -r, -z10) and H2 antigen complexes (H2: 1,2, -1,5, -1,6, 1,7 and H: enx, enz15). The results of mPCR showed 100% consistency with the serogroups determined by the conventional method. Both sensitivity and specificity of mPCR according to each serogroups were found to be 100%. Results of serotyping that have been determined with the molecular antigenic formula showed accurate results for 2 (2%), probable results for 91 (91%) and incomplete formula for 7 (7%) isolates. Molecular serotyping results of the most common isolated Salmonella serotypes of which S.Enteritidis, S.Typhimurium and S.Paratyphi from clinical microbiology laboratories have been determined as probable results. Antigenic formula of these serotypes that detected using mPCR were considered to be consistent with the results of conventional serotyping when interpreted with epidemiologic data. The sensitivity of mPCR to identify S.Typhi which have been determined as accurate result with molecular serotyping was 100% for serogrouping and serotyping. Multiplex PCR is cheaper and faster for the serotyping of strains isolated in clinical laboratories, compared to the conventional methods. However since it is not possible to detect all serotypes by using molecular typing, this technique can not be currently considered as an alternative for conventional serotyping. Nevertheless molecular typing could be beneficial in providing the preliminary results earlier. PMID- 24237439 TI - [Investigation of Chlamydia trachomatis seropositivity in patients with cervical cancer]. AB - Chlamydia trachomatis is the most frequent bacterial pathogen causing sexually transmitted diseases worldwide. Many studies emphasize that chlamydial infections may play role as a cofactor in cervical cancers caused by high risk human papillomavirus types. The aim of this study was to investigate the presence of antibodies specific for C.trachomatis in patients with cervical cancer in order to detect the frequency of chlamydial infections. A total of 77 patients diagnosed as cervical cancer who have undergone surgery and on treatment at Oncology Institute of Istanbul Faculty of Medicine were included in the study, together with 20 healthy women as the control group. Serum samples obtained from patient and control groups were investigated by a commercial microimmunofluorescence kit (Orgenium Laboratories, Finland) for the detection of C.trachomatis IgG, IgA and IgM antibodies. All of the control subjects (mean age: 30.25 +/- 6.4 years) were found seronegative, however the seropositivity rate detected in patients with cervical cancer was 9.1% (7/77). Serological data were interpreted as previous infections in four patients with single IgG positivity (titers: 1/16 in three and 1/32 in one patient), acute infections in two patients with IgG + IgM positivity (titers: IgG 1/64 and IgM 1/64 for both patients), and chronic infection in one patient with IgG + IgA positivity (titers: IgG 1/128 and IgA 1/20). The mean age of seven seropositive patients was 53.88 +/- 12.1 years, and three of them had antibodies against FGK, three against BDE and one against CHIJ serogroups of C.trachomatis. None of the cases had the history of sexually transmitted disease. No statistically significance was found between patient and control groups regarding C.trachomatis IgG, IgA and IgM seropositivity (for IgG; p= 0.339, for IgA; p= 1.000, for IgM; p= 1.000). However, it was thought that the statistical evaluations may not be conclusive due to the small number of study groups. In conclusion further studies with large numbers of cases are needed to understand the role of chlamydia infections in the development of cervical cancer. PMID- 24237440 TI - [Evaluation of zygomycosis cases by pooled analysis method reported from Turkey]. AB - Zygomycosis is a rapidly-progressive invasive fungal disease with high mortality rates. Mucor, Rhizopus, Rhizomucor and Absidia species classified in Mucorales order, are the main causative agents of zygomycosis. Uncontrolled diabetes, hematologic malignancies, long term corticosteroid use and immunosuppressive therapies are the main predisposing factors for mucormycosis. In this study, we aimed to evaluate the mucormycosis cases from Turkey published in national and international databases in the last 17 years by means of age, gender, co morbidities, signs and symptoms, diagnostic methods, therapeutic modalities, and mortality rate by pooling analysis. In our study, two national (http://uvt.ulakbim.gov.tr, http://www.turkmedline.net) and two international (www.ncbi.nlm.nih.gov, http://apps.webofknowledge.com) databases were used. A total of 64 manuscript (34 from national and 30 from international databases) published between 1995 and 2012, which were eligible for the study criteria and accessible as full text were included in the study. A total of 151 mucormycosis patients (71 female, 80 male; mean age: 45.4 +/- 21.4 years) from these studies, with definitive diagnosis of invasive fungal infections according to the criteria of European Organization for Research and Treatment of Cancer (EORTC) have been evaluated. Of 151 patients 91 (60%) were diagnosed as rhinocerebral, 42 (%27.8) were sinoorbital, 7 (4.6%) were pulmonary, 6 (3.9%) were disseminated, 3 (1.9%) were skin, and 2 (1.3%) were gastrointestinal mycormycosis. The most common symptoms and signs were; swelling of eye and face (n= 95, 63%), fever (n= 72, 48%), nasal obstruction (n= 60, 40%), headache (n= 58, 38%) and opthtalmoplegia (n= 48, 32%). The most common co-morbidity was diabetes (49%) followed by hematological malignancies (39.7%). Mycological cultures were performed for 82 patients, and fungal growth were detected in the clinical specimens of 51 cases. The distribution of strains isolated in culture were as follows: Mucor spp. (n= 19, 37.2%), Rhizopus spp. (n= 13, 25.5%), Zygomycetes (n= 9, 17.6%), Rhizopus oryzae (n= 4, 7.8%), Rhizopus spp. + yeast (n= 3, 5.9%), Rhizomucor spp. (n= 2, 3.9%) and Rhizosporium spp. (n= 1, 1.9%). In 133 patients, histopathological investigation and in 126 patients radiological examinations were performed for diagnosis. Both surgical debridement and antifungal therapy were employed in 115 patients. Four patients had received only surgical debridement and 30 only antifungal therapies. Classical amphotericin B (AMP-B) therapy for 77 cases, liposomal AMP-B for 60 cases, liposomal AMP-B + posaconazole for six cases and lipid complex AMP-B for two cases have been started as antifungal therapies. Total mortality rate was detected as 54.3% (82/151). In conclusion, despite new diagnostic tools and therapeutic agents, mortality rates in mucormycosis are still very high. For the management, mucormycosis should be considered early in risky patients, and surgical debridement together with effective antifungal therapy should be applied as soon as possible. PMID- 24237441 TI - [The first metronidazole-resistant Bacteroides species isolated at Marmara University Hospital: Bacteroides thetaiotaomicron]. AB - Bacteroides species, the predominant constituents of the human intestinal microbiota can cause serious intraabdominal and postoperative wound infections and bacteremia. Moreover, these bacteria are more resistant to antimicrobial agents than the other anaerobes. The limited number of the antimicrobials, such as carbapenems, beta-lactam/beta-lactamase inhibitors and nitroimidazoles are highly effective in eliminating Bacteroides. However, a few metronidazole resistant isolates have been reported from several countries recently. The nim genes (nim A-G) are suggested to be responsible for the majority of the metronidazole resistance. Here, we describe a metronidazole-resistant Bacteroides thetaiotaomicron isolated from a blood culture. A gram-negative obligate anaerobic rod was isolated from the postoperative 5th day blood culture of a 62 year-old male patient with adenocarcinoma of the pancreas head. The strain was identified as B.thetaiotaomicron by using a combination of conventional tests and commercially available biochemical kits. Antimicrobial susceptibility testing was performed by agar dilution method. The resistance genes were investigated by means of PCR using specific primer pairs for nim gene. The purified PCR product was sequenced and analyzed by comparison of the consensus sequences with GenBank sequences. The MIC for metronidazole was 16 mg/L. Although the strain was intermediate according the CLSI criteria, it was resistant (> 4 mg/L) according to EUCAST criteria. The isolate was nim gene positive, and nucleotide sequencing of the PCR product shared 100% similarity with nimE gene (emb |AM042593.1 |). On the other hand the isolate was susceptible to carbapenems and sulbactam ampicillin. Following administration of ampicillin-sulbactam, the patient's fever disappeared after 24 hours. The clinical condition improved considerably and he was discharged at day 8. The patient was followed up at the medical oncology clinic; however he died due to disease progression six months after surgery. Since anaerobic bacteremia is associated with high mortality rate, prompt diagnosis and proper management are critical. The studies on Bacteroides bacteremia have revealed adverse outcomes in patients receiving antibiotics to which the bacterium was resistant. In the present case, the metronidazole resistant organism would be reported as susceptible according to CLSI breakpoint value and on account of this result the treatment might lead to clinical failure. Therefore EUCAST MIC values seem to be more rational in case of Bacteroides antibiotic susceptibility testing. PMID- 24237442 TI - [Healthcare-associated Neisseria meningitidis W135 conjunctivitis]. AB - Neisseria meningitidis is an unusual pathogen among the causes of acute bacterial conjunctivitis. Meningococcal conjunctivitis may present as primary or secondary infection, while primary meningococcal conjunctivitis may emerge as invasive or non-invasive forms. N.meningitidis W135 strain is not common in Turkey, and is rarely reported as the cause of meningitis. Moreover, no cases of conjunctivitis due to N.meningitidis W135 were reported from Turkey. In this report a case of N.meningitidis W135 conjunctivitis has been presented who acquired the infection from another patient with meningococcal meningitis by close contact in the hospital environment. A 2-month-old male infant was admitted to our hospital with poor health condition, feeding difficulty and weight loss. He was hospitalized in intensive care unit and fluid replacement started due to severe dehydration. The infant had stigmata of Down's Syndrome, and since conjunctivitis were detected on physical examination, swab samples were obtained from both eyes for direct microscopic examination and cultivation. Abundant lekocytes and gram-negative diplococci were observed in Gram-stained smears, and bacterial growth were detected in the culture from left eye samples. The isolate have been identified as N.meningitidis by conventional microbiological methods, and serotyping of the isolate yielded W135 strain. The infant was treated with systemic cefotaxime and ampicillin-sulbactam, together with topical tobramycin and gentamycin. Since no symptoms of meningitis appeared during the follow-ups, the case was diagnosed as non-invasive primary meningococcal conjunctivitis. Investigation for a probable source revealed that the infant had close contact with a six-year-old boy with high fever, unconsciousness and vomiting a week ago in the outpatient clinic of Tekirdag State Hospital. N.meningitidis was also isolated from the cerebrospinal fluid culture of probable index case with meningitis and identified as W135 strain by serotyping. Both strains isolated from these cases were found similar according to their phenotypical characteristics, however genotyping could not be performed. Since no other sources of exposure could be found, it was concluded that the infant with conjunctivitis acquired the bacteria from the other patient during their shared hospital visit. This patient is the first N.meningitidis W135 conjunctivitis case reported from Turkey. PMID- 24237443 TI - [Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey]. AB - Fungal keratitis, an eye infection with poor prognosis, is difficult to treat and can lead to loss of vision. Among filamentous fungi Scedosporium spp. rarely lead to fungal keratitis. Here we present a case of keratitis caused by Scedosporium apiospermum. A 61-year-old female patient was admitted to our hospital with the complaints of right eye pain and decreased vision after a foreign body trauma to the right eye. The patient was diagnosed as keratitis by biomicroscopic examination. Conjunctival swabs collected from both eyes were inoculated onto sheep blood agar, chocolate agar, eosin methylene blue agar and Sabouraud dextrose agar. Corneal scrapings from the right eye were inoculated onto the same solid media by "C-streak" method, and in brain-heart-infusion broth by immersion. While gram-stained smears of conjunctival swabs showed no significant finding, smears of corneal scrapings revealed abundant neutrophils and profuse septate hyphae. Fungal keratitis was diagnosed and topical enhanced amphotericin B (0.5 mg/ml) therapy was initiated with netilmicin sulfate and oxytetracycline HCl plus polymyxin B sulfate. At the 10th day of therapy a mold growth was detected in corneal scraping cultures and was identified microscopically as S.apiospermum. Based on the relevant literature, therapy was changed to enhanced topical voriconazole (2 mg/ml) applied hourly, plus systemic voriconazole administration. At the third day of treatment, reduction of epithelial defect and decline in the focus of keratitis were observed. In the following days, however, a progression occurred in the focus of keratitis and 5% natamycin ophthalmic suspension was added to the therapy. Since the patient did not respond to any of the medical treatments, therapeutic penetrating keratoplasty was planned; yet, the patient refused the operation and was discharged with her own request. As far as the local literature was concerned, this is the first report of keratitis caused by S.apiospermum in Turkey. Though a very rare causative agent of keratitis, S.apiospermum is generally resistant to antifungal therapy and often require surgical treatment. Especially in patients with predisposing factors, this organism should be kept in mind as a potential causative agent and relevant microbiological examinations should be performed. PMID- 24237444 TI - [Three cases of fungemia caused by Blastoschizomyces capitatus]. AB - Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.capitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and amphotericin B after the identification of B.capitatus, and clinical improvement were noted during their follow-up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; BioMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45 degrees C and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 ug/ml for amphotericin B; 2, 2, 16 ug/ml for fluconazole; 0.064, 0.032, 0.032 ug/ml for itraconazole and 0.125, 0.064, 0.064 ug/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 ug/ml for voriconazole and > 32 ug/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence-based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between two (case 1 and 2) strains and 94.9% similarity in one strain (case 3) of B.capitatus, however the transmission route could not be clarified due to the absence of environmental sampling. In conclusion, B.capitatus should also be considered as a cause of systemic fungal infections in immunocompromised patients. Determination of the in vitro antifungal susceptibilities of clinical B.capitatus strains may contribute to the therapeutic approaches and epidemiological data. PMID- 24237445 TI - Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5. AB - We report the case of a male patient presenting with eosinophilia, pulmonary oedema and eosinophilic fasciitis (EF). He had the classic clinical appearance and magnetic resonance imaging of EF. Cytogenetic analysis of the bone marrow revealed a previously undescribed pericentric inversion of chromosome 5. Overall, the presentation was consistent with a diagnosis of chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS). Dermatologists should consult a haematologist in cases of EF, in order to rule out possible haematological malignancies. PMID- 24237446 TI - Outcomes of patients with fludarabine-refractory chronic lymphocytic leukemia: a population-based study from a well-defined geographic region. AB - Patients with fludarabine-refractory (FR) chronic lymphocytic leukemia (CLL) receive novel agents in pivotal, non-randomised phase-2 trials. Understanding outcome of FR-CLL in health-care may provide important contextual information. Records from 1301 patients (Stockholm-Cancer-Registry 1991-2010) identified 92 FR patients; bulky lymph-nodes (BFR-group), double-refractory (DR-group), or Others' group for outcome-analysis. Median age was 69 years 67% had Rai-stage III/IV with median 3 prior therapies. Overall response-rate was 20%; significantly lower in BFR (8%, p = 0.01) and DR (20%, p = 0.01) than in 'Others' (31%). Time-to treatment-failure (months) was significantly longer in 'Others' (9.2) than in BFR/DR (5.3/4.4) (p < 0.01) and significantly longer (p < 0.05) in antibody treated patients (9.1) compared to other regimens (5.2). Early-death occurred in 5%, >= grade III-infections in 20%. Median overall-survival (OS) was 18 months; 29 in BFR vs. 13 in DR (p = 0.054). Male sex was the only prognostic factor on OS (p = 0.01, HR 2.2, multivariate-Cox-regression). Our results, without external referrals, facilitate interpretation of non-randomised trials/novel drugs in advanced-stage-CLL. PMID- 24237447 TI - Oncogenic deregulation of NKL homeobox gene MSX1 in mantle cell lymphoma. AB - NKL homeobox gene MSX1 is physiologically expressed during embryonic hematopoiesis. Here, we detected MSX1 overexpression in three examples of mantle cell lymphoma (MCL) and one of acute myeloid leukemia (AML) by screening 96 leukemia/lymphoma cell lines via microarray profiling. Moreover, in silico analysis identified significant overexpression of MSX1 in 3% each of patients with MCL and AML, confirming aberrant activity in subsets of both types of malignancies. Comparative expression profiling analysis and subsequent functional studies demonstrated overexpression of histone acetyltransferase PHF16 together with transcription factors FOXC1 and HLXB9 as activators of MSX1 transcription. Additionally, we identified regulation of cyclin D1/CCND1 by MSX1 and its repressive cofactor histone H1C. Fluorescence in situ hybridization in MCL cells showed that t(11;14)(q13;q32) results in detachment of CCND1 from its corresponding repressive MSX1 binding site. Taken together, we uncovered regulators and targets of homeobox gene MSX1 in leukemia/lymphoma cells, supporting the view of a recurrent genetic network that is reactivated in malignant transformation. PMID- 24237448 TI - Lenalidomide consolidation and maintenance therapy after autologous stem cell transplant for multiple myeloma induces persistent changes in T-cell homeostasis. AB - Whether the efficacy of lenalidomide in the treatment of multiple myeloma (MM) is due to direct tumor toxicity only or to additional immunomodulatory effects is unclear. We studied the effect of lenalidomide treatment on T-cell immune reconstitution in patients with MM who had undergone autologous peripheral blood stem cell transplant (ASCT). Twenty-nine newly diagnosed patients with MM received induction therapy followed by high-dose melphalan and ASCT. After ASCT, 11 patients received lenalidomide consolidation therapy for 2 months followed by maintenance therapy until disease progression. The remaining 18 patients received no treatment. Serial analysis of thymic output, as given by numbers of T-cell receptor excision circles (sjTRECs), and T-cell phenotyping was performed until 18 months post-ASCT. Lenalidomide impaired long-term thymic T-cell reconstitution, decreased CD4 + and CD8 + CD45RA + CCR7 - effector-terminal T cell absolute counts and increased CD4 + CD25 + CD127 - /low regulatory T-cells. Lenalidomide consolidation and long-term maintenance therapy, administered post ASCT, may have a potentially negative impact on immune surveillance. PMID- 24237449 TI - Central nervous system involvement in chronic lymphocytic leukemia: uncommon manifestation with undefined therapeutic management. PMID- 24237450 TI - Hybridization and adaptation to introduced balloon vines in an Australian soapberry bug. AB - Contemporary adaptation of plant feeding insects to introduced hosts provides clear cases of ecologically based population divergence. In most cases the mechanisms permitting rapid differentiation are not well known. Here we study morphological and genetic variation associated with recent shifts by the Australian soapberry bug Leptocoris tagalicus onto two naturalized Neotropical balloon vines, Cardiospermum halicacabum and C. grandiflorum that differ in time since introduction. Our results show that these vines have much larger fruits than the native hosts (Whitewood tree -Atalaya hemiglauca- and Woolly Rambutan Alectryon tomentosus-) and that bugs living on them have evolved significantly longer beaks and new allometries. Genetic analyses of mitochondrial haplotypes and amplified fragment length polymorphic (AFLP) markers indicate that the lineage of bugs on the annual vine C. halicacabum, the older introduction, is intermediate between the two subspecies of L. tagalicus found on native hosts. Moreover, where the annual vine and Whitewood tree co-occur, the morphology and genomic composition of the bugs are similar to those occurring in allopatry. These results show that hybridization provided the genetic elements underlying the strongly differentiated 'Halicacabum bugs'. In contrast, the bugs feeding on the recently introduced perennial balloon vine (C. grandiflorum) showed no evidence of admixture, and are genetically indistinguishable from the nearby populations on a native host. PMID- 24237451 TI - The impact of intermediate time between chemotherapy and hypofractionated radiotherapy to the radiation induced skin toxicity for breast adjuvant treatment. AB - To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty-four patients with stage I-II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose-EQD2- 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow-up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late-toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy. PMID- 24237452 TI - Hypothermic machine perfusion versus cold storage in the rescuing of livers from non-heart-beating donor rats. AB - The aim of this work was to compare the efficiency of cold storage (CS) and hypothermic machine perfusion (HMP) methods of preserving grafts excised from non heart-beating donors that had suffered 45 minutes of warm ischemia. We developed a new solution for HMP to use in liver transplantation, based on BES, gluconate, and polyethylene glycol (BGP-HMP solution). After 24 h of HMP or CS, livers were reperfused at 37 degrees C with Krebs-Henseleit solution with added dextran. For both procedures, portal pressure and flow were measured and the intrahepatic resistance (IR) was calculated. The pH oscillations and enzyme activities (LDH, AST, and ALT) were evaluated for the perfusion buffer during normothermic reperfusion. O2 consumption of the liver, glycogen production, and bile flow were also measured during the normothermic reperfusion period. Portal flow and IR showed statistical differences (P < 0.05) between the two groups (n = 5). HMP with BGP-HMP solution resulted in higher values of portal flow and lower IR than CS with HTK solution. Enzyme release after 90 min of reperfusion did not show statistical differences between groups. With regard to bile flow and O2 consumption, livers preserved by both processes were able to produce bile, but livers preserved with HMP were able to take up more O2 than livers preserved by CS. PMID- 24237453 TI - Bismuth-halide oxidative addition and bismuth-carbon reductive elimination in platinum complexes containing chelating diphosphine ligands. AB - Reaction of BiX3 (X = Cl, Br, I) with [PtMe2(P-P)], (1a, P-P = dppm; 1b, P-P = dppe), occurs easily to yield a mixture of platinum(II) complexes [PtMeX(P-P)], 2, and [PtX2(P-P)], 3, and the binuclear complex [Pt2Me2(MU-X)(MU-dppm)2]X, 4. On the basis of (31)P NMR and UV-vis spectroscopy, a mechanism is proposed in which the rate determining step is conversion of the yellowish Pt(II)-BiX3 adduct BiI3.[PtMe2(dppm)], A, into the Pt(IV)-Bi(III) intermediate [PtMe2(BiX2)X(P-P)], IM1. Density functional theory (DFT) studies suggest that intermediate IM1 may be formed in acetone solution which undergoes the Bi-C reductive elimination process before formation of complexes 2 and 3. The structures of intermediates IM1 were theoretically determined using DFT calculations. In dilute acetone solution, as monitored by UV-vis spectroscopy, the oxidative addition processes follow first order kinetics. The overall reaction is slower for heavier halide. PMID- 24237454 TI - A keloid edge precut, preradiotherapy method in large keloid skin graft treatment. AB - BACKGROUND: Keloids are scars that extend beyond the borders of the original wound. They are difficult to cure because of their high recurrence rate, particularly in large keloids that require skin grafts. This article describes a study to compare the effectiveness of a new technique, a combination precut, preradiotherapy method, with the conventional surgical method of keloid skin graft treatment. METHODS: Fifty-three patients with chest wall keloids were treated from April 2005 to June 2011. Twenty-nine patients were treated with conventional surgery and radiotherapy. Keloids were removed from these patients, and their wounds were closed with skin grafts. If the grafts survived well, radiotherapy was applied, and the sutures were removed. Twenty-four patients were treated using the novel precut, preradiotherapy method. An incision was made down to the subcutaneous layer around the edge of the keloid, and radiotherapy was applied on the following day. Then the keloid was removed, and the wound was closed using a skin graft. Radiotherapy was applied for the second time when the graft was found to have survived. Patients underwent follow-up examinations 6 and 12 months after surgery. The scar at the operation site and aesthetic satisfaction were recorded and compared. RESULTS: The recurrence rate was 55.2% in the conventional group and 16.7% in the precut group, a significant difference (chi(2) = 6.73, p < .01). There was a significant difference in aesthetic satisfaction between the two groups, with 48.3% in the conventional group rating their satisfaction as poor versus 8.3% in the precut group (chi(2) = 7.50, p < .01). CONCLUSION: The precut, preradiotherapy strategy may be a promising treatment option for patients with large keloids that require excision and skin graft repair. PMID- 24237456 TI - MicroRNA levels are modulated in Aedes aegypti after exposure to Dengue-2. AB - To define microRNA (miRNA) involvement during arbovirus infection of Aedes aegypti, we mined deep sequencing libraries of Dengue type 2 (DENV2)-exposed mosquitoes. Three biological replicates for each timepoint [2, 4 and 9 days post exposure (dpe)] and treatment group allowed us to remove the outliers associated with sample-to-sample variability. Using edgeR (R Bioconductor), designed for use with replicate deep sequencing data, we determined the log fold-change (logFC) of miRNA levels [18-23 nucleotides (nt)]. The number of significantly modulated miRNAs increased from <= 5 at 2 and 4 dpe to 23 unique miRNAs by 9 dpe. Putative miRNA targets were predicted by aligning miRNAs to the transcriptome, and the list was reduced to include the intersection of hits found using the Miranda, PITA, and TargetScan algorithms. To further reduce false-positives, putative targets were validated by cross-checking them with mRNAs reported in recent DENV2 host response transcriptome reports; 4076 targets were identified. Of these, 464 gene targets have predicted miRNA-binding sites in 3' untranslated regions. Context-specific target functional groups include proteins involved in transport, transcriptional regulation, mitochondrial function, chromatin modification and signal transduction processes known to be required for viral replication and dissemination. The miRNA response is placed in context with other vector host response studies by comparing the predicted targets with those of transcriptome studies. Together, these data are consistent with the hypothesis that profound and persistent changes to gene expression occur in DENV2-exposed mosquitoes. PMID- 24237458 TI - Kinetic studies of the epimerization of diastereomeric pyrylium salts. AB - Chiral pyrylium salts are almost unknown in the literature, and none that are epimerizable have been reported prior to our work. Herein, we report two new epimerizable pyryliums and the kinetics of the diastereomeric equilibration of these and one other example. All of these required a careful analysis of the (1)H NMR spectrum to identify the stereoisomers, particularly for one of them. The temporal evolution of the relative isomeric concentrations was determined through acquisition of progressive NMR spectra. The base-catalyzed isomerization kinetics were successfully modeled as sequential, pseudo-first-order reactions that transition through a long-lived intermediate. These results suggest that the pseudobase intermediate is the operative catalyst when epimerizations are initiated with amines with pK(a) 7.4 or greater. Given the bulky nature of the operative acid (pyrylium) and base (pseudobase), the rate of these epimerizations is sensitive to steric bulk in the pyrylium. Thus, the reaction kinetics slow by a factor of 25 when substituents are placed at the ortho versus para position on the pyrylium cyclohexane ring. This is likely due to the difficulty of pseudobase attack at the sterically crowded pyrylium acidic hydrogen position. PMID- 24237457 TI - Arterial thromboembolism in 250 cats in general practice: 2004-2012. AB - BACKGROUND: Population characteristics and outcome of cats with arterial thromboembolism (ATE) managed in general practice (GP) have been poorly described. HYPOTHESIS: Cats with ATE presenting to GP are usually euthanized at presentation, but survival times >1 year are possible. ANIMALS: Cats with ATE managed by 3 GP clinics in the United Kingdom. METHODS: Records of cases presenting to GP over a 98-month period (2004-2012) were reviewed. Cats with an antemortem diagnosis of limb ATE were included. Outcome information was obtained. RESULTS: Over 98 months, 250 cats were identified with ATE. Prevalence was approximately 0.3%. At presentation, 153 cats (61.2%) were euthanized, with 68/97 (70.1%) of the remaining cats (27.2% of the total population) surviving >24 hours after presentation. Of these, 30/68 (44.1%) survived for at least 7 days. Hypothermia (HR, 1.44; 95% CI, 1.002-2.07; P = .049) and management by Clinic 2 (HR, 5.53; 95% CI, 1.23-24.8; P = .026) were independent predictors of 24-hour euthanasia or death. For cats surviving >24 hours, hypothermia (HR, 2.25; 95% CI, 1.12-4.48; P = .021) and failure to receive aspirin, clopidogrel, or both (HR, 8.26; 95% CI, 1.39-50; P = .001) were independent predictors of euthanasia or death within 7 days. For cats that survived >=7 days, median survival time was 94 (95% CI, 42-164) days, with 6 cats alive 1 year after presentation. CONCLUSIONS: Although 153/250 cats were euthanized at presentation, 6 cats survived >12 months. No factors were identified that predicted euthanasia on presentation. PMID- 24237459 TI - Observations of families in structured interactions: parenting therapists provide reliable ratings of mothers' parenting. AB - The reliability of observations of parenting by parenting therapists was assessed. An important predictor of externalizing behavior in children is quality of parenting. Data were videotapes of structured interactions in families with a child age 8-12 years referred to the evidence based Parent Management Training Oregon (PMTO) treatment program for child behavior problems. The therapists had clinical PMTO training but no training in systematic observation. PMTO observational coders with specific coder training were included as a reference for the therapists. Five therapists and two coders observed videotapes of 10 families and performed global evaluations of mothers' parenting skills. They used the coder's impression measure used in PMTO research. Scores were analyzed in a generalizability theory framework for the two groups of observers separately. Both observer types reliably rank-ordered the mothers and assessed the level of parenting skills. PMTO therapists without coder training provided reliable ratings of parenting constructs relevant to the clinical PMTO program in a manner comparable to that of the trained reference coders. PMID- 24237460 TI - Using comparative effectiveness research to inform decision-making: is there a role of economic evaluation? PMID- 24237461 TI - New approach presented in Norway for large-scale cancer screening programs. PMID- 24237462 TI - From methods to policy: actions speak louder than words. PMID- 24237463 TI - Comparative effectiveness research from the perspective of a surgeon-scientist. PMID- 24237464 TI - Novel lytics, novel imaging: a new treatment strategy in stroke? AB - Intravenous thrombolysis with alteplase is one of the few evidence-based acute ischemic stroke treatments. Efficacy is time dependent and not all patients treated within the 4.5 h license derive benefit. The lytic agent tenecteplase has theoretical benefits. In the Phase II study by Parsons and colleagues, tenecteplase was superior to alteplase across imaging and safety outcomes for patients selected using specific imaging criteria. We review the evidence for thrombolysis, experience with tenecteplase and compare this study with others that have used similar designs for the investigation of novel stroke lytic agents. PMID- 24237465 TI - Roflumilast as add-on therapy to conventional inhalers in COPD: a cost effectiveness analysis. AB - Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease that is mainly linked to smoking and is associated with significant medical and economic burdens. For example, in the USA the estimated direct costs are US$29.5 billion, whereas at the EU level these costs are estimated to amount to approximately 56% of the costs related to respiratory diseases. COPD is characterized by chronic respiratory symptoms such as dyspnea and productive cough, which are progressive and further worsen during exacerbation of the disease. It is also associated with an abnormal lung function decline and with an increasing rate of exacerbations, the latter being responsible for most of the related direct costs. The existing inhaled therapies such as long-acting anticholinergics, long-acting beta2 agonists and inhaled corticosteroids are not always able to improve the disease outcome, and therefore other more effective therapies are needed; roflumilast is a recent example of such a therapy, being authorized for use in patients with severe and very severe COPD (i.e., with a forced expiratory volume in 1 s of <50% predicted) based on its ability to significantly reduce the exacerbation rate and the severity of respiratory symptoms. PMID- 24237466 TI - Optimizing the design of pragmatic trials: key issues remain. AB - Clinical trials have largely focused on whether an intervention can work. To ensure valid and powerful testing of this hypothesis, trials attempt to maximize the effect of the intervention of interest, controlling other factors that can confound comparisons. The benefits observed in these studies are often not sustained once the treatment is used in routine care, leaving regulators, practitioners and patients with a paucity of reliable evidence to assist decision making. Attempts to address this need have led to 'pragmatic trials' that prioritize applicability of findings to real-world practice by minimizing design features that produce less pertinent information. Minimizing biases in this pragmatic context remains a very difficult task, however. This paper reviews some of these challenges and highlights specific aspects of design that must be approached with a pragmatic attitude. PMID- 24237467 TI - Assessing the impact of systematic reviews on future research: two case studies. AB - AIMS: To evaluate the impact of systematic reviews on research funded by the Agency for Healthcare Research and Quality (AHRQ) through Evidence-based Practice Centers (EPCs), and to identify barriers to and facilitators for the effects of these documents on future research. METHODS & MATERIALS: Two AHRQ systematic reviews were selected as case studies to evaluate their impact on future research. Key citations generated by these reports were identified through ISI Web of Science and PubMed Central and traced forward to identify effects on subsequent studies through citation analysis from updated systematic reviews on the topics. Requests for applications and program announcements from the NIH Guide for Grants and Contracts website were reviewed and dissemination data were obtained from AHRQ. Finally, interviews were conducted with 13 key informants to help identify short-, medium- and long-term impacts of the EPC reviews. RESULTS: The measurable impact of the two EPC reviews is demonstrably greater on short term outcomes (greater awareness of the issues) than on medium-term (e.g., the generation of new knowledge) or long-term outcomes (e.g., changes in patient practice or health outcomes). Factors such as the topic and the timing of the report relative to the development of the field may explain the impact of these two AHRQ reports. The degree to which the new research can be directly attributed to the AHRQ reviews remains unclear. Key informants discussed several benefits stemming from the EPC reports, including providing a foundation for the research community on which to build, heightening awareness of the gaps in knowledge, increasing the quality of research and sparking new directions of research. However, the degree to which these reports were influential hinged on several factors including marketing efforts, the very nature of the reports and other influences external to the EPC domain. CONCLUSIONS: The findings outlined in this article illustrate the importance of numerous factors influencing future research: the breadth, specificity and readiness of the topic for more research, ongoing developments in the field, availability of funding and active engagement of champions. AHRQ and the EPCs may be able to improve the likelihood of impact by creating more targeted products, planning for and expanding dissemination activities, improving the readability and other attributes of the reports themselves, and actively involving funders early on and throughout the process of creating and publishing the reviews. PMID- 24237468 TI - Comparing treatments for endometriosis-related pain symptoms in patients with migraine without aura. AB - Endometriosis is a gynecological disorder defined by the presence of endometrial like tissue outside the uterus. Several studies have found an epidemiological correlation between endometriosis and migraine, probably due to the association of both diseases with female hormones. Progestins or combined oral contraceptives are the first-line medical therapy in women with endometriosis; however, it is well known that in some women the use of combined oral contraceptives could exacerbate migraine. This observation poses a challenge to clinicians who must concomitantly treat endometriosis-related symptoms and migraine. This review summarizes the available literature on the medical treatment of endometriosis in women suffering concomitant migraine without aura until March 2012. Due to the lack of available studies on this topic, it is difficult to draw definitive conclusions. Further studies evaluating hormonal therapies are needed; in particular, progestin therapy should be reconsidered in women with migraine and concomitant endometriosis. PMID- 24237470 TI - [Standard prescriptions for extemporaneously produced medicinal preparations in pharmacies VI. Collection Neues Rezeptur-Formularium]. AB - The paper deals with the content of the collection Neues Rezeptur-Formularium (NRF) and some prescriptions potentially usable in innovations and standardization of prescriptions for extemporaneously produced medicinal preparations in pharmacies in the Czech Republic. Another possible use of NRF in the Czech Republic consists in the revision of the National Section of the Czech Pharmacopoeia. PMID- 24237471 TI - A combination of grapefruit seed extract and concentrated cranberry juice as a potential antimicrobial preservative for the improvement of microbiological stability of hypromellose gel. AB - Aqueous hypromellose gels are not microbiologically stable - they show signs of microorganism growth during storage. To extend the shelf-life of the gels, antimicrobial preservatives are needed. Some substances of plant origin are known for their antimicrobial properties, and thus they may be used as an alternative to synthetic preservatives. Therefore, the aim of this study was to evaluate the microbiological stability of aqueous hypromellose gel and the effectiveness of natural substances - grapefruit seed extract (GSE), concentrated cranberry juice, and a combination thereof - on the antimicrobial protection of the gel. The evaluation of the antimicrobial activity of GSE and cranberry juice showed that their antimicrobial effects differed. Both cranberry juice and GSE inhibited the growth of the standard gram-positive and gram-negative bacteria, but the effect of GSE was significantly stronger. Candida albicans was sensitive only to GSE. For this reason, in order to affect all the microorganisms studied, either a combination of 0.7% GSE and 10% cranberry juice, or 5% GSE alone may be used. The combination of GSE and cranberry juice was effective only in acidic medium (pH being 2.5-5), while the antimicrobial effect of GSE was not dependent on the pH value. PMID- 24237472 TI - [Evaluation of liberation of caffeine from dermal semisolids drugs]. AB - The paper deals with formulation of caffeine into dermal semisolid dosage forms - hydrogels. Caffeine was chosen as a model drug because its properties can be successfully used just in hydrogels. Protective and tranquilization effects can be used in the preparations for sunbathing, and its lipolytic and regenerative effect can be used for the treatment of androgenic alopecia or cellular bioprotection. The aim of the study was to investigate the influence of different concentrations of chitosan and caffeine on the liberation of gels. Besides, stability of the prepared samples was evaluated by means of the evaluation of their rheological parameters. Based on the obtained results, there was determined the optimal drug concentration - caffeine 0.2% (w/w) and also the gel forming substance - chitosan 2.3% (w/w). PMID- 24237473 TI - [Influence of temperature and concentration of a surfactant on pharmaceutical availability]. AB - This study aimed to analyze the influence of surfactant concentration and temperature on drug liberation from hydrogels and their flow properties. The surfactant benzethonium chloride (BZCl) was used in concentrations of 0.01, 0.1 and 0.5 % (w/w), while the drug chlorhexidine dihydrochloride (CHX) was used in a concentration of 0.1 % (w/w). Chitosan (CHIT) in 2.5 % (w/w) concentration was used as a gel-creating substance. The drug and surfactant liberation were evaluated within the temperature range of 25-40 degrees C. The largest amounts of both of them were liberated at the temperature of 40 degrees C. Through the concentration changes it was possible to obtain statistically significant differences (P < 0.05) between the liberation of CHX and BZCl. An analysis of the flow properties revealed that the character of the plastic system was not influenced by the changing concentration of the surfactant. The experimental results led to the conclusion that the optimum composition of the gel was as follows: 2.5 % (w/w) CHIT + 0.1 % (w/w) CHX + 0.01 % (w/w) BZCl. PMID- 24237474 TI - [Perception of body weight by pharmacists and pharmaceutical laboratory assistants in Slovakia I]. AB - The paper presents the results of a questionnaire poll carried out in the workers in pharmacies in the Slovak Republic in the year 2012. Altogether 1,884 questionnaires were distributed, of which 492 (26.1%) were returned. The poll aimed to find the perception of and attitudes to overweight and obesity in pharmacists and pharmaceutical laboratory assistants. The average BMI values in pharmacists were 25.08, in pharmaceutical laboratory assistants 24.86. Overweight and/or obesity were recorded in 36.6% of respondents, BMI 25 was found in 5.2 % men and 33.7% women. An absence of a chronic disease was reported in 61.8% of respondents, and 38.8% of respondents reported medication - most frequently administration of antihistamines, hormones of the thyroid gland, and antihypertensive drugs. In 220 (44.7%) of respondents, overweight/obesity existed in the family. Physical exercise carried out more than 3 times a week was reported by 9.6% of respondents. Drinking regime was evaluated as good in 52.1% of respondents, and 14.6% of participants compensated stress with food. PMID- 24237475 TI - [Perception of body weight by pharmacists and pharmaceutical laboratory assistants in Slovakia II]. AB - The paper presents the results of a questionnaire poll carried out in the workers in pharmacies in the Slovak Republic in the year 2012. A number of 250 respondents (50.8%) were satisfied with their weight, 242 (49.2%) were not satisfied; 190 (38.6%) of them attempted to decrease the weight, 52 (10.6%) did not; 94 persons (49.5 %) attempted to decrease weight more than 3 times. 110 respondents (57.9%) actively searched for the possibilities of treatment of overweight and obesity. The most frequent source of information was the Internet (64; 57.7%). Only 43 (22.6%) participants decided to solve their problem of overweight/obesity in cooperation with an expert. As many as 127 (66.8%) respondents stated that the physician did not draw their attention to the need of decreasing their weight. The most widely used method of slimming in the workers in pharmacies was modification of eating habits (162, 84.4%). A number of 108 (56.8%) respondents reported that they were able to maintain the loss of weight. PMID- 24237476 TI - Psychiatric symptomatology and health-related quality of life in children and adolescents with alopecia areata. AB - BACKGROUND: There is a very limited amount of data available regarding the relationship between alopecia areata (AA) and psychiatric morbidity and quality of life (QoL) in children and adolescents. OBJECTIVES: The aim of this study was to determine the psychiatric state and health-related quality of life (HRQL) of children and adolescents with AA, as well as their relationships with clinical parameters. METHODS: The sample consisted of 74 children with AA aged 8-18 years. Questionnaires were used to evaluate the psychiatric status and HRQL of the patients. The study and control groups were divided into child and adolescent groups to exclude the effect of puberty on psychological condition. RESULTS: In the child group, patients had higher state anxiety and trait anxiety scores; they also had lower parent-rated psychosocial and total area HRQL scores than the controls did. In addition, the depression score was prone to show a positive relationship with having AA in the children. In the adolescent group, however, only the state anxiety score had a significant association with AA. All of the parent-rated HRQL scores were also prone to being lower compared with controls in this age group. Regarding determinants of HRQL, prolonged disease duration and later disease onset had positive effects, whereas severity of scalp involvement, trait anxiety and depression had negative effects, for the sample as a whole. CONCLUSIONS: Alopecia areata is associated with poor psychiatric status and QoL, especially in childhood. The impact of the disease on QoL occurs through both clinical and psychiatric parameters. PMID- 24237477 TI - Three-dimensional imaging of whole mouse models: comparing nondestructive X-ray phase-contrast micro-CT with cryotome-based planar epi-illumination imaging. AB - In this study, we compare two evolving techniques for obtaining high-resolution 3D anatomical data of a mouse specimen. On the one hand, we investigate cryotome based planar epi-illumination imaging (cryo-imaging). On the other hand, we examine X-ray phase-contrast micro-computed tomography (micro-CT) using synchrotron radiation. Cryo-imaging is a technique in which an electron multiplying charge coupled camera takes images of a cryo-frozen specimen during the sectioning process. Subsequent image alignment and virtual stacking result in volumetric data. X-ray phase-contrast imaging is based on the minute refraction of X-rays inside the specimen and features higher soft-tissue contrast than conventional, attenuation-based micro-CT. To explore the potential of both techniques for studying whole mouse disease models, one mouse specimen was imaged using both techniques. Obtained data are compared visually and quantitatively, specifically with regard to the visibility of fine anatomical details. Internal structure of the mouse specimen is visible in great detail with both techniques and the study shows in particular that soft-tissue contrast is strongly enhanced in the X-ray phase images compared to the attenuation-based images. This identifies phase-contrast micro-CT as a powerful tool for the study of small animal disease models. PMID- 24237478 TI - Association between reduced kidney function and clinical outcomes after ischaemic stroke with atrial fibrillation. AB - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) can cause up to 50% of cardioembolic strokes and its effects may be exacerbated by chronic kidney disease. Our aim was to investigate the influence of reduced renal function on death, disability and stroke recurrence in stroke patients with AF in China. METHODS: In this prospective study, patients with ischaemic stroke and AF who were admitted within 1 month of stroke onset between January 2003 and February 2007 were consecutively enrolled. Patients were classified as having a reduced estimated glomerular filtration rate (eGFR) or normal eGFR, and clinical characteristics, functional outcomes and stroke recurrence were compared between the two groups. RESULTS: A total of 229 patients were analyzed in the study, of whom 105 (45.9%) had reduced eGFR. These patients were more likely to be female, non-smokers and non-drinkers than were patients in the normal eGFR group (all P <= 0.002). Patients with reduced eGFR showed approximately 2-fold higher risk of death at 3, 6 and 12 months after stroke onset than did patients with normal eGFR (all P <= 0.042), after adjusting for age, sex and stroke severity on admission. However, the two groups showed similar 1-year cumulative stroke recurrence (P = 0.331, log rank test). CONCLUSIONS: Reduced eGFR was independently associated with increased risk of death in patients with ischaemic stroke and AF. The association between reduced eGFR and risk of stroke recurrence needs to be explored in larger studies. PMID- 24237479 TI - Autism and developmental profiles in preschoolers: stability and change over time. AB - AIM: Increasing numbers of young children are now being diagnosed with autism spectrum disorder (ASD). This study aimed to analyse developmental trajectories in a representative group of preschool children with ASD. METHOD: In a naturalistic study, 208 preschool children with different subtypes of ASD were followed over a 2-year period. Their trajectories, as regards persistence of ASD diagnoses, developmental/intellectual levels, adaptive functioning and expressive speech, were monitored. RESULTS: Developmental profiles showed considerable change over time, especially in children with atypical autism and in those with developmental delay/borderline intellectual functioning at their first assessment. Approximately 50% of the children were found to have intellectual disability (ID) at follow-up and, of these, the majority had severe ID. This was in contrast to the first assessment by the referral team when ID had rarely been mentioned or discussed. CONCLUSION: Changes in developmental profiles during preschool years are common in children with ASD. This implies that reassessments, covering different developmental areas, are needed. Such follow-up assessments prior to the start of school will yield a more valid estimation of the child's general cognitive level and a more accurate ASD diagnosis and thus form a better basis for realistic educational planning and intervention. PMID- 24237480 TI - Claims for compensation after alleged birth asphyxia: a nationwide study covering 15 years. AB - OBJECTIVE: To analyze compensation claims with neurological sequela or death following alleged birth asphyxia. DESIGN: A cohort study. SETTING: A nationwide study in Norway. SAMPLE: All claims made to The Norwegian System of Compensation to Patients (NPE) concerning sequela related to alleged birth asphyxia, between 1994 and 2008. A total of 315 claims of which 161 were awarded compensation. METHODS: Examination of hospital records, experts' assessments and the decisions made by the NPE, the appeal body and courts of law. MAIN OUTCOME MEASURES: Characteristics of deliveries resulting in intrapartum asphyxia and causes of substandard care categorized in eight groups. RESULTS: In the 161 compensated cases, 107 children survived (96 with neurological sequela), and 54 children died. Human error was a frequent reason of substandard care, seen as inadequate fetal monitoring (50%), lack of clinical knowledge and skills (14%), noncompliance with clinical guidelines (11%), failure in referral for senior medical help (10%) and error in drug administration (4%). System errors were registered in only 3%, seen as poor organization of the department, lack of guidelines and time conflicts. The health personnel held responsible for substandard care was an obstetrician in 49% and a midwife in 46%. CONCLUSIONS: Substandard care is common in birth asphyxia, and human error is the cause in most cases. Inadequate fetal monitoring and lack of clinical knowledge and skills are the most frequent reasons for compensation after birth asphyxia. PMID- 24237481 TI - Phylogenetic constraints on elemental stoichiometry and resource allocation in heterotrophic marine bacteria. AB - The objective of this study was to evaluate the contribution of evolutionary history to variation in the biomass stoichiometry and underlying biochemical allocation patterns of heterotrophic marine bacteria. We hypothesized that phylogeny significantly constrains biochemical allocation strategy and elemental composition among taxa of heterotrophic marine bacteria. Using a 'common-garden' experimental design, we detected significant interspecific variation in stoichiometry, macromolecule allocation and growth rate among 13 strains of marine Proteobacteria. However, this variation was not well explained by 16S rRNA phylogenetic relationships or differences in growth rate. Heterotrophic bacteria likely experience C-limitation when consuming resources in Redfield proportions, which consequently decouples growth rate from allocation to rRNA and biomass P content. Accordingly, overall bacterial C : nutrient ratios (C : P = 77, C : N = 4.9) were lower than Redfield proportions, whereas the average N : P ratio of 17 was consistent with the Redfield ratio. Our results suggest that strain-level diversity is an important driver of variation in the C : N : P ratios of heterotrophic bacterial biomass and that the potential importance of non-nucleic acid pools of P warrants further investigation. Continued work clarifying the range and controls on the stoichiometry of heterotrophic marine bacteria will help improve understanding and predictions of global ocean C, N and P dynamics. PMID- 24237482 TI - Effectiveness of healthy relationships video-group-A videoconferencing group intervention for women living with HIV: preliminary findings from a randomized controlled trial. AB - INTRODUCTION: Expanded access to efficacious interventions is needed for women living with human immunodeficiency virus (WLH) in the United States. Availability of "prevention with (human immunodeficiency virus [HIV)] positives" interventions in rural/remote and low HIV prevalence areas remains limited, leaving WLH in these communities few options for receiving effective behavioral interventions such as Healthy Relationships (HR). Offering such programs via videoconferencing groups (VGs) may expand access. This analysis tests the effectiveness of HR-VG (versus wait-list control) for reducing sexual risk behavior among WLH and explores intervention satisfaction. SUBJECTS AND METHODS: In this randomized controlled trial unprotected vaginal/anal sex occasions over the prior 3 months reported at the 6-month follow-up were compared across randomization groups through zero-inflated Poisson regression modeling, controlling for unprotected sex at baseline. Seventy-one WLH were randomized and completed the baseline assessment (n=36 intervention and n=35 control); 59 (83% in each group) had follow-up data. RESULTS: Among those who engaged in unprotected sex at 6-month follow-up, intervention participants had approximately seven fewer unprotected occasions than control participants (95% confidence interval 5.43-7.43). Intervention participants reported high levels of satisfaction with HR-VG; 84% reported being "very satisfied" overall. CONCLUSIONS: This study found promising evidence for effective dissemination of HIV risk reduction interventions via VGs. Important next steps will be to determine whether VGs are effective with other subpopulations of people living with HIV (i.e., men and non-English speakers) and to assess cost-effectiveness. Possibilities for using VGs to expand access to other psychosocial and behavioral interventions and reduce stigma are discussed. PMID- 24237483 TI - Transglutamination allows production and characterization of native-sized ELPylated spider silk proteins from transgenic plants. AB - In the last two decades it was shown that plants have a great potential for production of specific heterologous proteins. But high cost and inefficient downstream processing are a main technical bottleneck for the broader use of plant-based production technology especially for protein-based products, for technical use as fibres or biodegradable plastics and also for medical applications. High-performance fibres from recombinant spider silks are, therefore, a prominent example. Spiders developed rather different silk materials that are based on proteins. These spider silks show excellent properties in terms of elasticity and toughness. Natural spider silk proteins have a very high molecular weight, and it is precisely this property which is thought to give them their strength. Transgenic plants were generated to produce ELPylated recombinant spider silk derivatives. These fusion proteins were purified by Inverse Transition Cycling (ITC) and enzymatically multimerized with transglutaminase in vitro. Layers produced by casting monomers and multimers were characterized using atomic force microscopy (AFM) and AFM-based nanoindentation. The layered multimers formed by mixing lysine- and glutamine-tagged monomers were associated with the highest elastic penetration modulus. PMID- 24237484 TI - Unusual nonrefractile eosinophilic crystal in breast ducts in a patient with invasive mucinous carcinoma. AB - A 72-year-old, G4P2 white woman presented with a recent abnormal mammogram showing a nodule at 8 o'clock of her right breast and indeterminate calcification in the subareolar region. An initial stereotactic core followed by wide local excision and sentinel node biopsy showed a pT1aN0(sn)M(na) low-grade invasive mucinous carcinoma. In dilated benign ducts, adjacent to the carcinoma, numerous eosinophilic, nonrefractile crystals were identified. PMID- 24237485 TI - How does emotion influence different creative performances? The mediating role of cognitive flexibility. AB - Cognitive flexibility is proposed to be one of the factors underlying how positive emotions can improve creativity. However, previous works have seldom set up or empirically measured an independent index to demonstrate its mediating effect, nor have they investigated its mediating role on different types of creative performances, which involve distinct processes. In this study, 120 participants were randomly assigned to positive, neutral or negative affect conditions. Their levels of cognitive flexibility were then measured by a switch task. Finally, their creative performances were calibrated by either an open ended divergent thinking test or a closed-ended insight problem-solving task. The results showed that positive emotional states could reduce switch costs and enhance both types of creative performances. However, cognitive flexibility exhibited a full mediating effect only on the relationship between positive emotion and insight problem solving, but not between positive emotion and divergent thinking. Divergent thinking was instead more associated with arousal level. These results suggest that emotions might influence different creative performances through distinct mechanisms. PMID- 24237486 TI - Improvement in lupus pernio with the successive use of pulsed dye laser and nonablative fractional resurfacing. PMID- 24237487 TI - Uncommon presentations of primary systemic necrotizing vasculitides: the Great Masquerades. AB - INTRODUCTION: Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature. METHODS: All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified. RESULTS: Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed. CONCLUSIONS: Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes. PMID- 24237489 TI - Editorial: Review changes. PMID- 24237488 TI - Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis. AB - BACKGROUND: Cadherin 12 (CDH12), which encodes a type II classical cadherin from the cadherin superfamily, may mediate calcium-dependent cell adhesion. It has been demonstrated that CDH12 could play an important role in the invasion and metastasis of salivary adenoid cystic carcinoma. We decided to investigate the relationship between CDH12 expression level and clinicopathologic variables in colorectal carcinoma (CRC) patients and to explore the functions of CDH12 in tumorigenesis in CRC. METHODS: The expression levels of CDH12 in colorectal carcinoma tissues were detected by immunohistochemistry. Real-time PCR and Western Blot were used to screen CDH12 high-expression cell lines. CCK-8 assay was used to detect the proliferation ability of CRC cells being transfected by shRNAs against CDH12. The wound assay and transwell assay were performed to test migration and invasion ability. The importance of CDH12 in cell-cell junctions was detected by cell adhesion assay and cell aggregation assay. Endothelial tube formation assay was used to test the influence of CDH12 on angiogenesis. RESULTS: Statistical analysis of clinical cases revealed that the positive rate of CDH12 was higher in the CRC tumor tissues compared with the adjacent non-tumor tissues. The expression levels of CDH12 in CRC patients are significantly correlated with invasion depth. Consistently, the ability of proliferation, migration and invasion were suppressed when CDH12 was decreased in CRC cells transfected with shRNAs. Cell adhesion assay and cell aggregation assay presented that tumor cells tend to disperse with the lack of CDH12. Endothelial tube formation assay showed that down-regulation of CDH12 could obviously inhibit the process of angiogenesis, implying that CDH12 may play an important role in tumor metastasis CONCLUSION: Our results showed that CDH12 promotes proliferation, migration, invasion, adhesion and angiogenesis, suggesting that CDH12 may be an oncogene in colorectal cancer. CDH12 is expected to become a new diagnostic and prognostic marker and a novel target of the treatment of colorectal cancer. PMID- 24237490 TI - Generation of massive entanglement through an adiabatic quantum phase transition in a spinor condensate. AB - We propose a method to generate massive entanglement in a spinor Bose-Einstein condensate from an initial product state through an adiabatic sweep of the magnetic field across a quantum phase transition induced by competition between the spin-dependent collision interaction and the quadratic Zeeman effect. The generated many-body entanglement is characterized by the experimentally measurable entanglement depth in the proximity of the Dicke state. We show that the scheme is robust to practical noise and experimental imperfection and under realistic conditions it is possible to generate genuine entanglement for hundreds of atoms. PMID- 24237491 TI - Geometry-induced Casimir suspension of oblate bodies in fluids. AB - We predict that a low-permittivity oblate body (disk-shaped object) above a thin metal substrate (plate with a hole) immersed in a fluid of intermediate permittivity will experience a metastable equilibrium (restoring force) near the center of the hole. Stability is the result of a geometry-induced transition in the sign of the force, from repulsive to attractive, that occurs as the disk approaches the hole--in planar or nearly planar geometries, the same material combination yields a repulsive force at all separations, in accordance with the Dzyaloshinskii-Lifshitz-Pitaevskii condition of fluid-induced repulsion between planar bodies. We explore the stability of the system with respect to rotations and lateral translations of the disks and demonstrate interesting transitions (bifurcations) in the rotational stability of the disks as a function of their size. Finally, we consider the reciprocal situation in which the disk-plate materials are interchanged and find that in this case the system also exhibits metastability. The forces in the system are sufficiently large to be observed in experiments and should enable measurements based on the diffusion dynamics of the suspended bodies. PMID- 24237492 TI - Matter-wave interferometry of a levitated thermal nano-oscillator induced and probed by a spin. AB - We show how the interference between spatially separated states of the center of mass (c.m.) of a mesoscopic harmonic oscillator can be evidenced by coupling it to a spin and performing solely spin manipulations and measurements (Ramsey interferometry). We propose to use an optically levitated diamond bead containing a nitrogen-vacancy center spin. The nanoscale size of the bead makes the motional decoherence due to levitation negligible. The form of the spin-motion coupling ensures that the scheme works for thermal states so that moderate feedback cooling suffices. No separate control or observation of the c.m. state is required and thereby one dispenses with cavities, spatially resolved detection, and low-mass-dispersion ensembles. The controllable relative phase in the Ramsey interferometry stems from a gravitational potential difference so that it uniquely evidences coherence between states which involve the whole nanocrystal being in spatially distinct locations. PMID- 24237493 TI - Simple hardy-like proof of quantum contextuality. AB - Contextuality and nonlocality are two fundamental properties of nature. Hardy's proof is considered the simplest proof of nonlocality and can also be seen as a particular violation of the simplest Bell inequality. A fundamental question is: Which is the simplest proof of contextuality? We show that there is a Hardy-like proof of contextuality that can also be seen as a particular violation of the simplest noncontextuality inequality. Interestingly, this new proof connects this inequality with the proof of the Kochen-Specker theorem, providing the missing link between these two fundamental results, and can be extended to an arbitrary odd number n of settings, an extension that can be seen as a particular violation of the n-cycle inequality. PMID- 24237494 TI - Experimental recovery of a qubit from partial collapse. AB - We describe and implement a method to restore the state of a single qubit, in principle perfectly, after it has partially collapsed. The method resembles the classical Hahn spin echo but works on a wider class of relaxation processes, in which the quantum state partially leaves the computational Hilbert space. It is not guaranteed to work every time, but successful outcomes are heralded. We demonstrate, using a single trapped ion, a better performance from this recovery method than can be obtained employing projection and postselection alone. The demonstration features a novel qubit implementation that permits both partial collapse and coherent manipulations with high fidelity. PMID- 24237495 TI - Gaussian error correction of quantum states in a correlated noisy channel. AB - Noise is the main obstacle for the realization of fault-tolerant quantum information processing and secure communication over long distances. In this work, we propose a communication protocol relying on simple linear optics that optimally protects quantum states from non-Markovian or correlated noise. We implement the protocol experimentally and demonstrate the near-ideal protection of coherent and entangled states in an extremely noisy channel. Since all real life channels are exhibiting pronounced non-Markovian behavior, the proposed protocol will have immediate implications in improving the performance of various quantum information protocols. PMID- 24237496 TI - Dynamically disordered quantum walk as a maximal entanglement generator. AB - We show that the entanglement between the internal (spin) and external (position) degrees of freedom of a qubit in a random (dynamically disordered) one dimensional discrete time quantum random walk (QRW) achieves its maximal possible value asymptotically in the number of steps, outperforming the entanglement attained by using ordered QRW. The disorder is modeled by introducing an extra random aspect to QRW, a classical coin that randomly dictates which quantum coin drives the system's time evolution. We also show that maximal entanglement is achieved independently of the initial state of the walker, study the number of steps the system must move to be within a small fixed neighborhood of its asymptotic limit, and propose two experiments where these ideas can be tested. PMID- 24237497 TI - Experimental bit commitment based on quantum communication and special relativity. AB - Bit commitment is a fundamental cryptographic primitive in which Bob wishes to commit a secret bit to Alice. Perfectly secure bit commitment between two mistrustful parties is impossible through asynchronous exchange of quantum information. Perfect security is however possible when Alice and Bob split into several agents exchanging classical and quantum information at times and locations suitably chosen to satisfy specific relativistic constraints. Here we report on an implementation of a bit commitment protocol using quantum communication and special relativity. Our protocol is based on [A. Kent, Phys. Rev. Lett. 109, 130501 (2012)] and has the advantage that it is practically feasible with arbitrary large separations between the agents in order to maximize the commitment time. By positioning agents in Geneva and Singapore, we obtain a commitment time of 15 ms. A security analysis considering experimental imperfections and finite statistics is presented. PMID- 24237498 TI - Optimally designed quantum transport across disordered networks. AB - We establish a general mechanism for highly efficient quantum transport through finite, disordered 3D networks. It relies on the interplay of disorder with centrosymmetry and a dominant doublet spectral structure and can be controlled by the proper tuning of only coarse-grained quantities. Photosynthetic light harvesting complexes are discussed as potential biological incarnations of this design principle. PMID- 24237499 TI - Dynamical steady States in driven quantum systems. AB - We derive dynamical equations for a driven, dissipative quantum system in which the environment-induced relaxation rate is comparable to the Rabi frequency, avoiding assumptions on the frequency dependence of the environmental coupling. When the environmental coupling varies significantly on the scale of the Rabi frequency, secular or rotating wave approximations break down. We avoid these approximations, yielding dynamical steady states which account for the interaction between driven quantum dots and their phonon environment. The theory, which is motivated by recent experimental observations, qualitatively and quantitatively describes the transition from asymmetric unsaturated resonances at weak driving to population inversion at strong driving. PMID- 24237500 TI - Information thermodynamics on causal networks. AB - We study nonequilibrium thermodynamics of complex information flows induced by interactions between multiple fluctuating systems. Characterizing nonequilibrium dynamics by causal networks (i.e., Bayesian networks), we obtain novel generalizations of the second law of thermodynamics and the fluctuation theorem, which include an informational quantity characterized by the topology of the causal network. Our result implies that the entropy production in a single system in the presence of multiple other systems is bounded by the information flow between these systems. We demonstrate our general result by a simple model of biochemical adaptation. PMID- 24237501 TI - Nonadditive entropies yield probability distributions with biases not warranted by the data. AB - Different quantities that go by the name of entropy are used in variational principles to infer probability distributions from limited data. Shore and Johnson showed that maximizing the Boltzmann-Gibbs form of the entropy ensures that probability distributions inferred satisfy the multiplication rule of probability for independent events in the absence of data coupling such events. Other types of entropies that violate the Shore and Johnson axioms, including nonadditive entropies such as the Tsallis entropy, violate this basic consistency requirement. Here we use the axiomatic framework of Shore and Johnson to show how such nonadditive entropy functions generate biases in probability distributions that are not warranted by the underlying data. PMID- 24237502 TI - Gamma-ray-burst beaming and gravitational-wave observations. AB - Using the observed rate of short-duration gamma-ray bursts (GRBs) it is possible to make predictions for the detectable rate of compact binary coalescences in gravitational-wave detectors. We show that the nondetection of mergers in the existing LIGO/Virgo data constrains the beaming angles and progenitor masses of gamma-ray bursts, although these limits are fully consistent with existing expectations. We make predictions for the rate of events in future networks of gravitational-wave observatories, finding that the first detection of a neutron star-neutron-star binary coalescence associated with the progenitors of short GRBs is likely to happen within the first 16 months of observation, even in the case of only two observatories (e.g., LIGO-Hanford and LIGO-Livingston) operating at intermediate sensitivities (e.g., advanced LIGO design sensitivity, but without signal recycling mirrors), and assuming a conservative distribution of beaming angles (e.g., all GRBs beamed within theta(j) = 30 degrees ). Less conservative assumptions reduce the waiting time until first detection to a period of weeks to months, with an event detection rate of >/~10/yr. Alternatively, the compact binary coalescence model of short GRBs can be ruled out if a binary is not seen within the first two years of operation of a LIGO Hanford, LIGO-Livingston, and Virgo network at advanced design sensitivity. We also demonstrate that the gravitational wave detection rate of GRB triggered sources (i.e., those seen first in gamma rays) is lower than the rate of untriggered events (i.e., those seen only in gravitational waves) if theta(j)?30 degrees , independent of the noise curve, network configuration, and observed GRB rate. The first detection in gravitational waves of a binary GRB progenitor is therefore unlikely to be associated with the observation of a GRB. PMID- 24237503 TI - Cosmic evolution from phase transition of three-dimensional flat space. AB - Flat space cosmology spacetimes are exact time-dependent solutions of three dimensional gravity theories, such as Einstein gravity or topologically massive gravity. We exhibit a novel kind of phase transition between these cosmological spacetimes and the Minkowski vacuum. At sufficiently high temperature, (rotating) hot flat space tunnels into a universe described by flat space cosmology. PMID- 24237504 TI - New limits on primordial black hole dark matter from an analysis of Kepler source microlensing data. AB - We present new limits on the allowed masses of a dark matter (DM) halo consisting of primordial black holes (PBH) (or any other massive compact halo object). We analyze two years of data from the Kepler satellite, searching for short-duration bumps caused by gravitational microlensing. After removing background events consisting of variable stars, flare events, and comets or asteroids moving through the Kepler field, we find no microlensing candidates. We measure the efficiency of our selection criteria by adding millions of simulated microlensing lensing events into the Kepler light curves. We find that PBH DM with masses in the range 2 * 10(-9) M[Symbol: see text] to 10(-7)M[Symbol: see text] cannot make up the entirety of the DM in the Milky Way. At the low-mass end, this decreases the allowed mass range by more than an order of magnititude. PMID- 24237505 TI - From full stopping to transparency in a holographic model of heavy ion collisions. AB - We numerically simulate planar shock wave collisions in anti-de Sitter space as a model for heavy ion collisions of large nuclei. We uncover a crossover between two different dynamical regimes as a function of the collision energy. At low energies the shocks first stop and then explode in a manner approximately described by hydrodynamics, in close similarity with the Landau model. At high energies the receding fragments move outwards at the speed of light, with a region of negative energy density and negative longitudinal pressure trailing behind them. The rapidity distribution of the energy density at late times around midrapidity is not approximately boost invariant but Gaussian, albeit with a width that increases with the collision energy. PMID- 24237506 TI - eta and eta' mixing from lattice QCD. AB - We present a lattice QCD computation of eta and eta' masses and mixing angles, for the first time controlling continuum and quark mass extrapolations. The results for M(eta) = 551(8)(stat) (6)(yst) MeV and M(eta') = 1006(54)(stat)(38)(syst)(+61)(ex) MeV are in excellent agreement with experiment. Our data show that the mixing in the quark flavor basis can be described by a single mixing angle of O = 46(1)(stat)(3)(syst) degrees indicating that the eta' is mainly a flavor singlet state. PMID- 24237508 TI - Magnetic susceptibility of strongly interacting matter across the deconfinement transition. AB - We propose a method to determine the total magnetic susceptibility of strongly interacting matter by lattice QCD simulations and present numerical results for the theory with two light flavors, which suggest a weak magnetic activity in the confined phase and the emergence of strong paramagnetism in the deconfined, quark gluon plasma phase. PMID- 24237510 TI - Bayesian approach to spectral function reconstruction for Euclidean quantum field theories. AB - We present a novel approach to the inference of spectral functions from Euclidean time correlator data that makes close contact with modern Bayesian concepts. Our method differs significantly from the maximum entropy method (MEM). A new set of axioms is postulated for the prior probability, leading to an improved expression, which is devoid of the asymptotically flat directions present in the Shanon-Jaynes entropy. Hyperparameters are integrated out explicitly, liberating us from the Gaussian approximations underlying the evidence approach of the maximum entropy method. We present a realistic test of our method in the context of the nonperturbative extraction of the heavy quark potential. Based on hard thermal-loop correlator mock data, we establish firm requirements in the number of data points and their accuracy for a successful extraction of the potential from lattice QCD. Finally we reinvestigate quenched lattice QCD correlators from a previous study and provide an improved potential estimation at T=2.33T(C). PMID- 24237511 TI - Decisive test of color coherence in proton-nucleus collisions at the LHC. AB - Proton-nucleus collisions (p+A) at LHC energies provide a rigorous test of color glass condensate (CGC), a model proposed to describe the high energy limit of quantum chromodynamics. In the CGC the average multiplicity of charged particles at midrapidity in p+A collisions depends logarithmically on the number of participants, N(part). In contrast, the wounded nucleon model of independent nucleon-nucleon scatterings, verified at RHIC energies, predicts that multiplicity in p+A depends linearly on N(part). We argue that the dependence of mean multiplicity on N(part) in p+A collisions at LHC energies can single out a model of particle production, thus offering a stringent test of the CGC and the wounded nucleon model. Based on this observation we propose a novel experimental test of color coherence in p+A collisions. PMID- 24237512 TI - Scattering-free optical levitation of a cavity mirror. AB - We demonstrate the feasibility of levitating a small mirror using only radiation pressure. In our scheme, the mirror is supported by a tripod where each leg of the tripod is a Fabry-Perot cavity. The macroscopic state of the mirror is coherently coupled to the supporting cavity modes allowing coherent interrogation and manipulation of the mirror motion. The proposed scheme is an extreme example of the optical spring, where a mechanical oscillator is isolated from the environment and its mechanical frequency and macroscopic state can be manipulated solely through optical fields. We model the stability of the system and find a three-dimensional lattice of trapping points where cavity resonances allow for buildup of optical field sufficient to support the weight of the mirror. Our scheme offers a unique platform for studying quantum and classical optomechanics and can potentially be used for precision gravitational field sensing and quantum state generation. PMID- 24237513 TI - Luminescence of oxygen atoms stimulated by metastable helium at cryogenic temperatures. AB - We present investigations of the afterglow of oxygen-helium gas mixtures at cryogenic temperatures. The cooling of a helium jet containing trace amounts of oxygen after passing through a radio frequency discharge zone led to the observation of strong emissions from atomic oxygen. The effect results from the increasing efficiency of energy transfer from metastable helium atoms and molecules to oxygen impurities in the cold dense helium vapor. This effect might find an application for the detection of small quantities of the impurities in helium gas. PMID- 24237514 TI - Dipolar confinement-induced resonances of ultracold gases in waveguides. AB - We develop a nonperturbative theoretical framework to treat collisions with generic anisotropic interactions in quasi-one-dimensional geometries. Our method avoids the limitations of pseudopotential theory and allows us to include accurately long-range anisotropic interactions. For ultracold dipolar collisions in a harmonic waveguide we predict dipolar confinement-induced resonances (DCIRs) which are attributed to different angular momentum states. The analytically derived resonance condition reveals in detail the interplay of the confinement with the anisotropic nature of the dipole-dipole interactions. The results are in excellent agreement with ab initio numerical calculations confirming the robustness of the presented approach. The exact knowledge of the positions of DCIRs may pave the way for the experimental realization of, e.g., Tonks-Girardeau like or super-Tonks-Girardeau-like phases in effective one-dimensional dipolar gases. PMID- 24237515 TI - Origin of collision-induced molecular orientation. AB - Collision-induced rotational angular momentum orientation is a fundamental property of molecular scattering, which is sensitive to the balance between attractive and repulsive forces at play during collision. Here, we quantify a new mechanism leading to orientation, which is purely quantum mechanical in origin. Although the new mechanism is quite general, and will operate more widely in atomic and molecular scattering, it is observed here for impulsive hard shell collisions, for which the orientation vanishes classically. The quantum mechanism can thus be studied in isolation from other processes. The orientation is proposed to originate from the nonlocal nature of the quantum mechanical collision encounter. PMID- 24237516 TI - Experimental evidence of twin fast metastable H(2(2)S) atoms from dissociation of cold H2 induced by electrons. AB - We report the direct detection of two metastable H(2^{2}S) atoms coming from the dissociation of a single cold H(2) molecule, in coincidence measurements. The molecular dissociation was induced by electron impact in order to avoid limitations by the selection rules governing radiative transitions. Two detectors, placed close to the collision center, measure the neutral metastable H(2(2)S) through a localized quenching process, which mixes the H(2^{2}S) state with the H(2^{2}P), leading to a Lyman-alpha detection. Our data show the accomplishment of a coincidence measurement which proves for the first time the existence of the H(2(2)S)-H(2(2)S) dissociation channel. PMID- 24237517 TI - Noncompeting channel approach to pair creation in supercritical fields. AB - The Dirac and Klein-Gordon equations are solved on a space-time grid to study the strong-field induced pair creation process for bosons and fermions from the vacuum. If the external field is sufficiently strong to induce bound states that are embedded in the negative energy continuum, a complex scaling technique of the Hamiltonian can predict the longtime behavior of the dynamics. In the case of multiple bound states this technique predicts the occurrence of a new collective time scale. The longtime behavior of the pair creation is not determined by a single (most important) channel, but collectively by the sum of all individual widths of the embedded states. PMID- 24237518 TI - Adaptive quantum state tomography improves accuracy quadratically. AB - We introduce a simple protocol for adaptive quantum state tomography, which reduces the worst-case infidelity [1-F(rho,rho)] between the estimate and the true state from O(1/sqrt[N]) to O(1/N). It uses a single adaptation step and just one extra measurement setting. In a linear optical qubit experiment, we demonstrate a full order of magnitude reduction in infidelity (from 0.1% to 0.01%) for a modest number of samples (N ~ 3 * 10(4)). PMID- 24237519 TI - Spectral engineering of slow light, cavity line narrowing, and pulse compression. AB - More than 4 orders of magnitude of cavity-linewidth narrowing in a rare-earth-ion doped crystal cavity, emanating from strong intracavity dispersion caused by off resonant interaction with dopant ions, is demonstrated. The dispersion profiles are engineered using optical pumping techniques creating significant semipermanent but reprogrammable changes of the rare-earth absorption profiles. Several cavity modes are shown within the spectral transmission window. Several possible applications of this phenomenon are discussed. PMID- 24237520 TI - Multimode plasmon excitation and in situ analysis in top-down fabricated nanocircuits. AB - We experimentally demonstrate synthesis and in situ analysis of multimode plasmonic excitations in two-wire transmission lines supporting a symmetric and an antisymmetric eigenmode. To this end we irradiate an incoupling antenna with a diffraction-limited excitation spot exploiting a polarization- and position dependent excitation efficiency. Modal analysis is performed by recording the far field emission of two mode-specific spatially separated emission spots at the far end of the transmission line. To illustrate the power of the approach we selectively determine the group velocities of symmetric and antisymmetric contributions of a multimode ultrafast plasmon pulse. PMID- 24237521 TI - Experimental observation of a fundamental length scale of waves in random media. AB - Waves propagating through a weakly scattering random medium show a pronounced branching of the flow accompanied by the formation of freak waves, i.e., extremely intense waves. Theory predicts that this strong fluctuation regime is accompanied by its own fundamental length scale of transport in random media, parametrically different from the mean free path or the localization length. We show numerically how the scintillation index can be used to assess the scaling behavior of the branching length. We report the experimental observation of this scaling using microwave transport experiments in quasi-two-dimensional resonators with randomly distributed weak scatterers. Remarkably, the scaling range extends much further than expected from random caustics statistics. PMID- 24237522 TI - Molecular dynamics simulation of the motion of colloidal nanoparticles in a solute concentration gradient and a comparison to the continuum limit. AB - Chemical-mechanical transduction mechanisms which can actuate the movement of colloids through liquids are highly sought after as engines to propel miniaturized micro- and nanobots. One mechanism involves harnessing the long range van der Waals attractive forces between the colloid and solute molecules dissolved in the liquid around the particle. If a concentration gradient of this solute is applied across the particle, then the imbalance in the van der Waals attraction drives the particle towards the higher concentration of solute. We present a molecular dynamics simulation using Lennard-Jones interactions between molecules of the solvent, solute, and colloid cluster which include short-range repulsive and long-range attractive potentials. The simulations demonstrate that a solute gradient can propel nanosized colloids, and that the velocity decreases with the colloid size. The solute-colloid short-range repulsive interactions are observed to be restricted to a region of specifically adsorbed solutes on the particle surface which are symmetrically adsorbed and do not contribute to the motion. The size of this region provides a cutoff for a continuum level description of the motion, and with this cutoff, continuum calculations are in excellent agreement with the molecular dynamics simulation results, completing a description of the propulsion from the nano- to the microscale. PMID- 24237509 TI - Measurement of the differential cross section dsigma/d(costheta(t)) for Top-Quark Pair Production in pp Collisions at sqrt[s] = 1.96 TeV. AB - We report a measurement of the differential cross section dsigma/d(costheta(t)) for top-quark pair production as a function of the top-quark production angle in proton-antiproton collisions at sqrt[s] = 1.96 TeV. This measurement is performed using data collected with the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.4 fb(-1). We employ the Legendre polynomials to characterize the shape of the differential cross section at the parton level. The observed Legendre coefficients are in good agreement with the prediction of the next-to-leading-order standard-model calculation, with the exception of an excess linear-term coefficient a(1) = 0.40 +/- 0.12, compared to the standard-model prediction of a(1)=0.15(-0.03)(+0.07). PMID- 24237523 TI - Transition of planar Couette flow at infinite Reynolds numbers. AB - An outline of the state space of planar Couette flow at high Reynolds numbers (Re<10^{5}) is investigated via a variety of efficient numerical techniques. It is verified from nonlinear analysis that the lower branch of the hairpin vortex state (HVS) asymptotically approaches the primary (laminar) state with increasing Re. It is also predicted that the lower branch of the HVS at high Re belongs to the stability boundary that initiates a transition to turbulence, and that one of the unstable manifolds of the lower branch of HVS lies on the boundary. These facts suggest HVS may provide a criterion to estimate a minimum perturbation arising transition to turbulent states at the infinite Re limit. PMID- 24237524 TI - Nanobubble collapse on a silica surface in water: billion-atom reactive molecular dynamics simulations. AB - Cavitation bubbles occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate damage caused by shock-induced collapse of nanobubbles in water near an amorphous silica surface. Collapse of an empty bubble generates a high-speed nanojet, which causes pitting on the silica surface. We find pit radii are close to bubble radii, and experiments also indicate linear scaling between them. The gas-filled bubbles undergo partial collapse and, consequently, the damage on the silica surface is mitigated. PMID- 24237525 TI - Coherent-radiation spectroscopy of few-femtosecond electron bunches using a middle-infrared prism spectrometer. AB - Modern, high-brightness electron beams such as those from plasma wakefield accelerators and free-electron laser linacs continue the drive to ever-shorter bunch durations. In low-charge operation (~20 pC), bunches shorter than 10 fs are reported at the Linac Coherent Light Source (LCLS). Though suffering from a loss of phase information, spectral diagnostics remain appealing as compact, low-cost bunch duration monitors suitable for deployment in beam dynamics studies and operations instrumentation. Progress in middle-infrared (MIR) imaging has led to the development of a single-shot, MIR prism spectrometer to characterize the corresponding LCLS coherent beam radiation power spectrum for few-femtosecond scale bunch length monitoring. In this Letter, we report on the spectrometer installation as well as the temporal reconstruction of 3 to 60 fs-long LCLS electron bunch profiles using single-shot coherent transition radiation spectra. PMID- 24237526 TI - Pressurized H2 RF cavities in ionizing beams and magnetic fields. AB - A major technological challenge in building a muon cooling channel is operating rf cavities in multitesla external magnetic fields. We report the first proof-of principle experiment of a high pressure gas-filled rf cavity for use with intense ionizing beams and strong external magnetic fields. rf power consumption by beam induced plasma is investigated with hydrogen and deuterium gases with pressures between 20 and 100 atm and peak rf gradients between 5 and 50 MV/m. The low pressure case agrees well with an analytical model based on electron and ion mobilities. Varying concentrations of oxygen gas are investigated to remove free electrons from the cavity and reduce the rf power consumption. Measurements of the electron attachment time to oxygen and rate of ion-ion recombination are also made. Additionally, we demonstrate the operation of the gas-filled rf cavity in a solenoidal field of up to 3 T, finding no major magnetic field dependence. All these results indicate that a high pressure gas-filled cavity is a viable technology for muon ionization cooling. PMID- 24237507 TI - Observation of the decay B(c)(+) -> B(s)(0)pi+. AB - The result of a search for the decay B(c)(+) -> B(s)(0) pi+ is presented, using the B(s)(0) -> D(s)(-)pi+ and B(s)(0) -> J/psi O channels. The analysis is based on a data sample of pp collisions collected with the LHCb detector, corresponding to an integrated luminosity of 1 fb(-1) taken at a center-of-mass energy of 7 TeV, and 2 fb(-1) taken at 8 TeV. The decay B(c)(+) -> B(s)(0)pi+ is observed with significance in excess of 5 standard deviations independently in both decay channels. The measured product of the ratio of cross sections and branching fraction is [sigma(B(c)(+))/sigma(B(s)(0))] * B(B(c)(+)-> B(s)(0)pi+) = [2.37 +/- 0.31 (stat)+/- 0.11 (syst)(-0.13)(+0.17)(tau(B)(c)(+)))] * 10(-3), in the pseudorapidity range 210(19) W/cm(2). A maximum increase by a factor of 2.5 of the cutoff energy of protons produced by target normal sheath acceleration is observed with respect to plane targets, around the incidence angle expected for the resonant excitation of surface waves. A significant enhancement is also observed for small angles of incidence, out of resonance. PMID- 24237528 TI - Focusing of an explosive plasma expansion in a transverse magnetic field. AB - The dynamics of a laser ablation plasma expanding in an external magnetic field have been investigated with imaging interferometry and shadowgraphy. The diagnostics reveal a new interaction mechanism, namely, the redirection of the explosive plasma expansion into a converging flow. A comparison with three dimensional ideal magnetohydrodynamic simulation results supports the observation that the efficient lateral plasma confinement causes the plasma to converge on the axis and initiate a directed flow. The resulting collimated flow propagates across the magnetic field in a kinetic regime, which cannot be modeled within the same framework. PMID- 24237529 TI - Dynamic circulation in a complex plasma. AB - The dynamic circulation of dust particles in a cylindrical complex plasma is studied experimentally. A levitated cloud of charged dust particles rotates around an axis in an ion flow induced by the coupling of applied magnetic field with the electric field due to plasma density gradient. The vertical and horizontal cross sections of the cloud reveal the dynamic circulation with helical trajectories of dust particles with meridional ascending motion near the axis. The dust particles in the center bottom in the cloud remain near a stagnation point and act like tea leaves in a teacup as described by Einstein in 1926. PMID- 24237530 TI - Realization of the Hofstadter Hamiltonian with ultracold atoms in optical lattices. AB - We demonstrate the experimental implementation of an optical lattice that allows for the generation of large homogeneous and tunable artificial magnetic fields with ultracold atoms. Using laser-assisted tunneling in a tilted optical potential, we engineer spatially dependent complex tunneling amplitudes. Thereby, atoms hopping in the lattice accumulate a phase shift equivalent to the Aharonov Bohm phase of charged particles in a magnetic field. We determine the local distribution of fluxes through the observation of cyclotron orbits of the atoms on lattice plaquettes, showing that the system is described by the Hofstadter model. Furthermore, we show that for two atomic spin states with opposite magnetic moments, our system naturally realizes the time-reversal-symmetric Hamiltonian underlying the quantum spin Hall effect; i.e., two different spin components experience opposite directions of the magnetic field. PMID- 24237531 TI - Realizing the Harper Hamiltonian with laser-assisted tunneling in optical lattices. AB - We experimentally implement the Harper Hamiltonian for neutral particles in optical lattices using laser-assisted tunneling and a potential energy gradient provided by gravity or magnetic field gradients. This Hamiltonian describes the motion of charged particles in strong magnetic fields. Laser-assisted tunneling processes are characterized by studying the expansion of the atoms in the lattice. The band structure of this Hamiltonian should display Hofstadter's butterfly. For fermions, this scheme should realize the quantum Hall effect and chiral edge states. PMID- 24237532 TI - Meron ground state of Rashba spin-orbit-coupled dipolar bosons. AB - We study the effects of dipolar interactions on a Bose-Einstein condensate with synthetically generated Rashba spin-orbit coupling. The dipolar interaction we consider includes terms that couple spin and orbital angular momentum in a way perfectly congruent with the single-particle Rashba coupling. We show that this internal spin-orbit coupling plays a crucial role in the rich ground-state phase diagram of the trapped condensate. In particular, we predict the emergence of a thermodynamically stable ground state with a meron spin configuration. PMID- 24237533 TI - Quantum quasicrystals of spin-orbit-coupled dipolar bosons. AB - We study quasi-two-dimensional dipolar Bose gases in which the bosons experience a Rashba spin-orbit coupling. We show that the degenerate dispersion minimum due to the spin-orbit coupling, combined with the long-range dipolar interaction, can stabilize a number of quantum crystalline and quasicrystalline ground states. Coupling the bosons to a fermionic species can further stabilize these phases. We estimate that the crystalline and quasicrystalline phases should be detectable in realistic dipolar condensates, e.g., dysprosium, and discuss their symmetries and excitations. PMID- 24237534 TI - Nonequilibrium quantum magnetism in a dipolar lattice gas. AB - We report on the realization of quantum magnetism using a degenerate dipolar gas in an optical lattice. Our system implements a lattice model resembling the celebrated t-J model. It is characterized by a nonequilibrium spinor dynamics resulting from intersite Heisenberg-like spin-spin interactions provided by nonlocal dipole-dipole interactions. Moreover, due to its large spin, our chromium lattice gases constitute an excellent environment for the study of quantum magnetism of high-spin systems, as illustrated by the complex spin dynamics observed for doubly occupied sites. PMID- 24237535 TI - From classical to quantum glasses with ultracold polar molecules. AB - We study the dynamics of a bilayer system of ultracold polar molecules, which exhibits classical and quantum glassy behavior, characterized by long tails in the relaxation time and dynamical heterogeneity. In the proposed setup, quantum fluctuations are of the order of thermal fluctuations and the degree of frustration can be tuned by the interlayer distance. We discuss the possible observation of a glassy anomalous diffusion and dynamical heterogeneity in experiment using internal degrees of freedom of the molecules in combination with optical detection. PMID- 24237536 TI - Artificial graphene with tunable interactions. AB - We create an artificial graphene system with tunable interactions and study the crossover from metallic to Mott insulating regimes, both in isolated and coupled two-dimensional honeycomb layers. The artificial graphene consists of a two component spin mixture of an ultracold atomic Fermi gas loaded into a hexagonal optical lattice. For strong repulsive interactions, we observe a suppression of double occupancy and measure a gapped excitation spectrum. We present a quantitative comparison between our measurements and theory, making use of a novel numerical method to obtain Wannier functions for complex lattice structures. Extending our studies to time-resolved measurements, we investigate the equilibration of the double occupancy as a function of lattice loading time. PMID- 24237537 TI - Measurement of elastic waves induced by the reflection of light. AB - The reflection of light from the surface of an elastic solid gives rise to various types of elastic waves that propagate inside the solid. The weakest waves are generally those that are generated by the radiation pressure acting during the reflection of the light. Here, we present the first quantitative measurement of such light-pressure-induced elastic waves inside an ultrahigh-reflectivity mirror. Amplitudes of a few picometers were observed at the rear side of the mirror with a displacement-measuring conical piezoelectric sensor when laser pulses with a fluence of 1 J/cm(2) were reflected from the front side of the mirror. PMID- 24237538 TI - Coexistence of scale-invariant states in incompressible elastomers. AB - Cavitation and sulcification of soft elastomers are two examples of thresholdless, nonlinear instabilities that evade detection by linearization. I show that the onset of such instabilities can be understood as a kind of phase coexistence between multiple scale-invariant states, and I constructively enumerate the possible scale-invariant states of incompressible rubber in two dimensions. Whereas true phases (like the affine deformations of rubber) are homogeneous, the alternatives are inhomogeneous. In terms of the thermodynamics of solids, both classes of states must generally be given equal consideration. PMID- 24237539 TI - Translational and rotational diffusion in water in the Gigapascal range. AB - First measurements of the self-dynamics of liquid water in the GPa range are reported. The GPa range has here become accessible through a new setup for the Paris-Edinburgh press specially conceived for quasielastic neutron scattering studies. A direct measurement of both the translational and rotational diffusion coefficients of water along the 400 K isotherm up to 3 GPa, corresponding to the melting point of ice VII, is provided and compared with molecular dynamics simulations. The translational diffusion is observed to strongly decrease with pressure, though its variation slows down for pressures higher than 1 GPa and decouples from that of the shear viscosity. The rotational diffusion turns out to be insensitive to pressure. Through comparison with structural data and molecular dynamics simulations, we show that this is a consequence of the rigidity of the first neighbors shell and of the invariance of the number of hydrogen bonds of a water molecule under high pressure. These results show the inadequacy of the Stokes-Einstein-Debye equations to predict the self-diffusive behavior of water at high temperature and high pressure, and challenge the usual description of hot dense water behaving as a simple liquid. PMID- 24237540 TI - Cooperative assembly of magic number C60-Au complexes. AB - We report the assembly of magic number (C60)m-(Au)n complexes on the Au(111) surface. These complexes have a unique structure consisting of a single atomic layer Au island wrapped by a self-selected number (seven, ten, or twelve) of C(60) molecules. The smallest structure consisting of 7 C60 molecules and 19 Au atoms, stable up to 400 K, has a preferred orientation on the surface. We propose a globalized metal-organic coordination mechanism for the stability of the (C(60))(m)-(Au)n complexes. PMID- 24237541 TI - Rotation of a single acetylene molecule on Cu(001) by tunneling electrons in STM. AB - We study the elementary processes behind one of the pioneering works on scanning tunneling microscope controlled reactions of single molecules [Stipe et al., Phys. Rev. Lett. 81, 1263 (1998)]. Using the Keldysh-Green function approach for the vibrational generation rate in combination with density functional theory calculations to obtain realistic parameters we reproduce the experimental rotation rate of an acetylene molecule on a Cu(100) surface as a function of bias voltage and tunneling current. This combined approach allows us to identify the reaction coordinate mode of the acetylene rotation and its anharmonic coupling with the C-H stretch mode. We show that three different elementary processes, the excitation of C-H stretch, the overtone ladder climbing of the hindered rotational mode, and the combination band excitation together explain the rotation of the acetylene molecule on Cu(100). PMID- 24237542 TI - Interacting living polymers confined between two surfaces. AB - We present predictions on the equilibrium behavior of solutions of living polymers confined in a gap between surfaces, including the ensuing potential of mean force between those surfaces (the disjoining potential). We highlight the occurrence of a transition upon narrowing the gap, which arises from a cooperative simultaneous increase of the local density and degree of polymerization. At this transition, many properties of the confined solution, including the disjoining potential, change by orders of magnitude over a minute change of the surface separation. These results were obtained owing to two extensions to a previously introduced self-consistent field-propagator formalism. (i) We derive this formalism from a free-energy functional of the distribution of chain lengths and configurations. This enables evaluation of thermodynamic properties, including the disjoining potential. (ii) We solved for a system confined between two surfaces. PMID- 24237543 TI - Magnetic-field-tuned Aharonov-Bohm oscillations and evidence for non-Abelian anyons at nu = 5/2. AB - We show that the resistance of the nu = 5/2 quantum Hall state, confined to an interferometer, oscillates with the magnetic field consistent with an Ising-type non-Abelian state. In three quantum Hall interferometers of different sizes, resistance oscillations at nu = 7/3 and integer filling factors have the magnetic field period expected if the number of quasiparticles contained within the interferometer changes so as to keep the area and the total charge within the interferometer constant. Under these conditions, an Abelian state such as the (3, 3, 1) state would show oscillations with the same period as at an integer quantum Hall state. However, in an Ising-type non-Abelian state there would be a rapid oscillation associated with the "even-odd effect" and a slower one associated with the accumulated Abelian phase due to both the Aharonov-Bohm effect and the Abelian part of the quasiparticle braiding statistics. Our measurements at nu = 5/2 are consistent with the latter. PMID- 24237544 TI - Proposal for a phonon laser utilizing quantum-dot spin states. AB - We propose a nanoscale realization of a phonon laser utilizing phonon-assisted spin flips in quantum dots to amplify sound. Owing to a long spin relaxation time, the device can be operated in a strong pumping regime, in which the population inversion is close to its maximal value allowed under Fermi statistics. In this regime, the threshold for stimulated emission is unaffected by spontaneous spin flips. Considering a nanowire with quantum dots defined along its length, we show that a further improvement arises from confining the phonons to one dimension, and thus reducing the number of phonon modes available for spontaneous emission. Our work calls for the development of nanowire-based, high finesse phonon resonators. PMID- 24237545 TI - Ultrahigh bandwidth spin noise spectroscopy: detection of large g-factor fluctuations in highly-n-doped GaAs. AB - We advance all optical spin noise spectroscopy (SNS) in semiconductors to detection bandwidths of several hundred gigahertz by employing a sophisticated scheme of pulse trains from ultrafast laser oscillators as an optical probe. The ultrafast SNS technique avoids the need for optical pumping and enables nearly perturbation free measurements of extremely short spin dephasing times. We apply the technique to highly-n-doped bulk GaAs where magnetic field dependent measurements show unexpected large g-factor fluctuations. Calculations suggest that such large g-factor fluctuations do not necessarily result from extrinsic sample variations but are intrinsically present in every doped semiconductor due to the stochastic nature of the dopant distribution. PMID- 24237547 TI - Quantum theory of magnetoelectromotive instability in nanoelectromechanical systems with positive differential conductance. AB - We consider dc-electronic transport through a nanowire suspended between two normal-metal leads in the presence of an external magnetic field. We show the very mechanism through which such a system, whose stationary current-voltage characteristic is essentially characterized by positive differential conductance, becomes unstable with respect to an onset of self-excited oscillations in electrical transport and mechanical vibrations. The self-excitation mechanism is based on the correlation between the occupancy of the quantized spin-split electronic energy levels inside the nanowire and the velocity of the nanowire with the crucial influence of strong enough retardation effects in magnetomotive coupling coming from mechanical vibrations. PMID- 24237546 TI - Diffusion-limited current in organic metal-insulator-metal diodes. AB - An analytical expression for the diffusion current in organic metal-insulator metal diodes is derived. The derivation is based on the classical diffusion theory of Schottky, with adaptations to account for the absence of doping, a built-in voltage due to asymmetric contacts, and band bending at the Ohmic contact. The commonly observed deviation of the ideality factor from unity (~1.2) is characteristic of diffusion-limited currents in undoped organic semiconductors. Summing with the classical space-charge limited current provides a full analytic description of the current as a function of voltage, temperature and layer thickness. PMID- 24237548 TI - Topological insulators with SU(2) Landau levels. AB - We construct continuum models of 3D and 4D topological insulators by coupling spin-1/2 fermions to an SU(2) background gauge field, which is equivalent to a spatially dependent spin-orbit coupling. Higher dimensional generalizations of flat Landau levels are obtained in the Landau-like gauge. The 2D helical Dirac modes with opposite helicities and 3D Weyl modes with opposite chiralities are spatially separated along the third and fourth dimensions, respectively. Stable 2D helical Fermi surfaces and 3D chiral Fermi surfaces appear on open boundaries, respectively. The charge pumping in 4D Landau level systems shows quantized 4D quantum Hall effect. PMID- 24237549 TI - Tunable band topology reflected by fractional quantum Hall States in two dimensional lattices. AB - Two-dimensional lattice models subjected to an external effective magnetic field can form nontrivial band topologies characterized by nonzero integer band Chern numbers. In this Letter, we investigate such a lattice model originating from the Hofstadter model and demonstrate that the band topology transitions can be realized by simply introducing tunable longer-range hopping. The rich phase diagram of band Chern numbers is obtained for the simple rational flux density and a classification of phases is presented. In the presence of interactions, the existence of fractional quantum Hall states in both |C| = 1 and |C| > 1 bands is confirmed, which can reflect the band topologies in different phases. In contrast, when our model reduces to a one-dimensional lattice, the ground states are crucially different from fractional quantum Hall states. Our results may provide insights into the study of new fractional quantum Hall states and experimental realizations of various topological phases in optical lattices. PMID- 24237550 TI - Topological superconductivity and Majorana fermions in RKKY systems. AB - We consider quasi-one-dimensional Ruderman-Kittel-Kasuya-Yosida (RKKY) systems in proximity to an s-wave superconductor. We show that a 2k(F) peak in the spin susceptibility of the superconductor in the one-dimensional limit supports helical order of localized magnetic moments via RKKY interaction, where k(F) is the Fermi wave vector. The magnetic helix is equivalent to a uniform magnetic field and very strong spin-orbit interaction (SOI) with an effective SOI length 1/2k(F). We find the conditions to establish such a magnetic state in atomic chains and semiconducting nanowires with magnetic atoms or nuclear spins. Generically, these systems are in a topological phase with Majorana fermions. The inherent self-tuning of the helix to 2k(F) eliminates the need to tune the chemical potential. PMID- 24237551 TI - Doping-dependent photon scattering resonance in the model high-temperature superconductor HgBa2CuO4+delta revealed by Raman scattering and optical ellipsometry. AB - We study the model high-temperature superconductor HgBa(2)CuO(4+delta) with electronic Raman scattering and optical ellipsometry over a wide doping range. The dependence of the resonant Raman cross section on the incident photon energy changes drastically as a function of doping, in a manner that corresponds to a rearrangement of the interband optical transitions seen with ellipsometry. This doping-dependent Raman resonance allows us to reconcile the apparent discrepancy between Raman and x-ray detection of magnetic fluctuations in superconducting cuprates. Intriguingly, the strongest variation occurs across the doping level where the antinodal superconducting gap appears to reach its maximum. PMID- 24237552 TI - Proposed measurement of spatial correlations at the Berezinski-Kosterlitz Thouless transition of superconducting thin films. AB - The Berezinski-Kosterlitz-Thouless transition is a unique two-dimensional phase transition, separating two phases with exponentially and power-law decaying correlations, respectively. In disordered systems, these correlations propagate along favorable paths, with the transition marking the point where global coherence is lost. Here we propose an experimental method to probe locally these particular paths in superconducting thin films, which exhibit this transition, and demonstrate theoretically that close to the transition the coherence propagates along a ramified network, reminiscent of a percolation transition. We suggest and calculate experimentally accessible quantities that can shed light on the spatial correlations in the system as it approaches the critical point. This approach can be applicable to a variety of phase transitions in disordered systems. PMID- 24237553 TI - Absence of static loop-current magnetism at the apical oxygen site in HgBa2CuO4+delta from NMR. AB - The simple structure of HgBa(2)CuO(4+delta) (Hg1201) is ideal among cuprates for study of the pseudogap phase as a broken symmetry state. We have performed (17)O nuclear magnetic resonance on an underdoped Hg1201 crystal with a transition temperature of 74 K to look for circulating loop currents proposed theoretically and inferred from neutron scattering. The narrow spectra preclude static local fields in the pseudogap phase at the apical site, suggesting that the moments observed with neutrons are fluctuating. The nuclear magnetic resonance frequency shifts are consistent with a dipolar field from the Cu(2+) site. PMID- 24237554 TI - Transverse spin Seebeck effect versus anomalous and planar Nernst effects in Permalloy thin films. AB - Transverse magnetothermoelectric effects are studied in Permalloy thin films grown on MgO and GaAs substrates and compared to those grown on suspended SiN(x) membranes. The transverse voltage along platinum strips patterned on top of the Permalloy films is measured versus the external magnetic field as a function of the angle and temperature gradients. After the identification of the contribution of the planar and anomalous Nernst effects, we find an upper limit for the transverse spin Seebeck effect, which is several orders of magnitude smaller than previously reported. PMID- 24237556 TI - Magnetic dephasing in mesoscopic spin glasses. AB - We have measured universal conductance fluctuations in the metallic spin glass Ag:Mn as a function of temperature and magnetic field. From this measurement, we can access the phase coherence time of the electrons in the spin glass. We show that this phase coherence time increases with both the inverse of the temperature and the magnetic field. From this, we deduce that decoherence mechanisms are still active even deep in the spin glass phase. PMID- 24237555 TI - Spin-1/2 XXZ chain system Cs2CoCl4 in a transverse magnetic field. AB - Comparing high-resolution specific heat and thermal expansion measurements to exact finite-size diagonalization, we demonstrate that Cs(2)CoCl(4) for a magnetic field along the crystallographic b axis realizes the spin-1/2 XXZ chain in a transverse field. Exploiting both thermal as well as virtual excitations of higher crystal-field states, we find that the spin chain is in the XY limit with an anisotropy J(z)/J[perpindicular] ~ 0.12, substantially smaller than previously believed. A spin-flop Ising quantum phase transition occurs at a critical field of MU(0)H(b)(cr) ~ 2 T before around 3.5 T the description in terms of an effective spin-1/2 chain becomes inapplicable. PMID- 24237557 TI - Electric control of exchange bias training. AB - Voltage-controlled exchange bias training and tunability are introduced. Isothermal voltage pulses are used to reverse the antiferromagnetic order parameter of magnetoelectric Cr(2)O(3), and thus continuously tune the exchange bias of an adjacent CoPd film. Voltage-controlled exchange bias training is initialized by tuning the antiferromagnetic interface into a nonequilibrium state incommensurate with the underlying bulk. Interpretation of these hitherto unreported effects contributes to new understanding in electrically controlled magnetism. PMID- 24237558 TI - Striped spin liquid crystal ground state instability of kagome antiferromagnets. AB - The Dirac spin liquid ground state of the spin 1/2 Heisenberg kagome antiferromagnet has potential instabilities. This has been suggested as the reason why it does not emerge as the ground state in large-scale numerical calculations. However, previous attempts to observe these instabilities have failed. We report on the discovery of a projected BCS state with lower energy than the projected Dirac spin liquid state which provides new insight into the stability of the ground state of the kagome antiferromagnet. The new state has three remarkable features. First, it breaks spatial symmetry in an unusual way that may leave spinons deconfined along one direction. Second, it breaks the U(1) gauge symmetry down to Z(2). Third, it has the spatial symmetry of a previously proposed "monopole" suggesting that it is an instability of the Dirac spin liquid. The state described herein also shares a remarkable similarity to the distortion of the kagome lattice observed at low Zn concentrations in Zn paratacamite and in recently grown single crystals of volborthite suggesting it may already be realized in these materials. PMID- 24237559 TI - Explosive electromagnetic radiation by the relaxation of a multimode magnon system. AB - Microwave emission from a parametrically pumped ferrimagnetic film of yttrium iron garnet was studied versus the magnon density evolution, which was detected by Brillouin light scattering spectroscopy. It has been found that the shutdown of external microwave pumping leads to an unexpected effect: The conventional monotonic decrease of the population of parametrically injected magnons is accompanied by an explosive behavior of electromagnetic radiation at the magnon frequency. The developed theory shows that this explosion is caused by a nonlinear energy transfer from parametrically driven short-wavelength dipolar exchange magnons to a long-wavelength dipolar magnon mode effectively coupled to an electromagnetic wave. PMID- 24237560 TI - Optically induced coupling of two magnetic dopant spins by a photoexcited hole in a Mn-doped InAs/GaAs quantum dot. AB - We report evidence of a photoinduced coupling between two spins provided by Mn dopants in their neutral acceptor state A(0) in a single InAs/GaAs quantum dot. The coupling occurs due to simultaneous exchange interactions between each of the two dopant spins and a photocreated hole. Microphotoluminescence spectroscopy achieved both in longitudinal and perpendicular magnetic fields reveals the splitting of the four spin configurations |J(1) = +/- 1,J(2) = +/- 1} due to the 2A(0)-hole exchange interaction. We obtain a comprehensive interpretation of the experimental data with a simplified spin Hamiltonian model, which more specifically shows that the hole-mediated coupling is similar to a epsilon(12)-70 MUeV exchange interaction between both A(0) spins. PMID- 24237561 TI - Ultrawideband dispersion control of a metamaterial surface for perfectly-matched layer-like absorption. AB - Narrow bandwidth is a fundamental issue plaguing practical applications of metamaterial absorbers. In this Letter, we show that by deliberately controlling the dispersion and dissipation of a metamaterial, an ultrawideband perfect metamaterial absorber with complex-valued constitutive parameters strictly satisfying the modified model of a perfectly matched layer, can be achieved. The nearly perfect power absorption, better than 99%, was experimentally observed in an unprecedented bandwidth of 39%, approaching the theoretical Rozanov limit. We expect a wide range of applications to emerge from this general concept. PMID- 24237562 TI - Persistent photoconductivity in strontium titanate. AB - Persistent photoconductivity was observed in strontium titanate (SrTiO(3)) single crystals. When exposed to sub-bandgap light (2.9 eV or higher) at room temperature, the free-electron concentration increases by over 2 orders of magnitude. After the light is turned off, the enhanced conductivity persists for several days, with negligible decay. From positron lifetime measurements, the persistent photoconductivity is attributed to the excitation of an electron from a titanium vacancy defect into the conduction band, with a very low recapture rate. PMID- 24237563 TI - Measurement of a photoinduced transition from a nonordered phase to a transient ordered phase in the organic quantum-paraelectric compound dimethyltetrathiafulvalene-dibromodichloro-p-benzoquinone using femtosecond laser irradiation. AB - We report a new photoinduced transition from a nonordered phase to a transient ordered phase with symmetry breaking in an organic charge-transfer compound, dimethyltetrathiafulvalene (DMTTF)-dibromodichloro-p-benzoquinone (2,6QBr(2)Cl(2)), which is a neutral compound located near the neutral-ionic phase boundary and shows quantum paraelectricity at low temperatures. By an irradiation of a femtosecond laser pulse, an ionic domain consisting of ~40 molecules is introduced into the neutral lattice per photon, giving rise to coherent molecular oscillations with fractional charge modulations over ~400 molecules. This response is due to the recovery of ferroelectric nature from the quantum paraelectricity by a photoinjection of an ionic domain with a large dipole moment. PMID- 24237564 TI - Energy loss at propagating jamming fronts in granular gas clusters. AB - We explore the initial moments of impact between two dense granular clusters in a two-dimensional geometry. The particles are composed of solid CO(2) and are levitated on a hot surface. Upon collision, the propagation of a dynamic "jamming front" produces a distinct regime for energy dissipation in a granular gas in which the translational kinetic energy decreases by over 90%. Experiments and associated simulations show that the initial loss of kinetic energy obeys a power law in time DeltaE = -Kt(3/2), a form that can be predicted from kinetic arguments. PMID- 24237565 TI - Patchy particle model for vitrimers. AB - Vitrimers--a recently invented new class of polymers--consist of covalent networks that can rearrange their topology via a bond shuffling mechanism, preserving the total number of network links. We introduce a patchy particle model whose dynamics directly mimic the bond exchange mechanism and reproduce the observed glass-forming ability. We calculate the free energy of this model in the limit of strong (chemical) bonds between the particles, both via the Wertheim thermodynamic perturbation theory and using computer simulations. The system exhibits an entropy-driven phase separation between a network phase and a dilute cluster gas, bringing new insight into the swelling behavior of vitrimers in solvents. PMID- 24237566 TI - Fluid mixing by curved trajectories of microswimmers. AB - We consider the tracer diffusion D(rr) that arises from the run-and-tumble motion of low Reynolds number swimmers, such as bacteria. Assuming a dilute suspension, where the bacteria move in uncorrelated runs of length lambda, we obtain an exact expression for D(rr) for dipolar swimmers in three dimensions, hence explaining the surprising result that this is independent of lambda. We compare D(rr) to the contribution to tracer diffusion from entrainment. PMID- 24237567 TI - Geometrical optics of dense aerosols: forming dense plasma slabs. AB - Assembling a freestanding, sharp-edged slab of homogeneous material that is much denser than gas, but much more rarefied than a solid, is an outstanding technological challenge. The solution may lie in focusing a dense aerosol to assume this geometry. However, whereas the geometrical optics of dilute aerosols is a well-developed field, the dense aerosol limit is mostly unexplored. Yet controlling the geometrical optics of dense aerosols is necessary in preparing such a material slab. Focusing dense aerosols is shown here to be possible, but the finite particle density reduces the effective Stokes number of the flow, a critical result for controlled focusing. PMID- 24237568 TI - Origin of overstretching transitions in single-stranded nucleic acids. AB - We combined single-molecule force spectroscopy with nuclear magnetic resonance measurements and molecular mechanics simulations to examine overstretching transitions in single-stranded nucleic acids. In single-stranded DNA and single stranded RNA there is a low-force transition that involves unwinding of the helical structure, along with base unstacking. We determined that the high-force transition that occurs in polydeoxyadenylic acid single-stranded DNA is caused by the cooperative forced flipping of the dihedral angle formed between four atoms, O5'-C5'-C4'-C3' (gamma torsion), in the nucleic acid backbone within the canonical B-type helix. The gamma torsion also flips under force in A-type helices, where the helix is shorter and wider as compared to the B-type helix, but this transition is less cooperative than in the B type and does not generate a high-force plateau in the force spectrums of A-type helices. We find that a similar high-force transition can be induced in polyadenylic acid single-stranded RNA by urea, presumably due to disrupting the intramolecular hydrogen bonding in the backbone. We hypothesize that a pronounced high-force transition observed for B-type helices of double stranded DNA also involves a cooperative flip of the gamma torsion. These observations suggest new fundamental relationships between the canonical structures of single-and double-stranded DNA and the mechanism of their molecular elasticity. PMID- 24237569 TI - Temporal networks: slowing down diffusion by long lasting interactions. AB - Interactions among units in complex systems occur in a specific sequential order, thus affecting the flow of information, the propagation of diseases, and general dynamical processes. We investigate the Laplacian spectrum of temporal networks and compare it with that of the corresponding aggregate network. First, we show that the spectrum of the ensemble average of a temporal network has identical eigenmodes but smaller eigenvalues than the aggregate networks. In large networks without edge condensation, the expected temporal dynamics is a time-rescaled version of the aggregate dynamics. Even for single sequential realizations, diffusive dynamics is slower in temporal networks. These discrepancies are due to the noncommutability of interactions. We illustrate our analytical findings using a simple temporal motif, larger network models, and real temporal networks. PMID- 24237570 TI - Comment on "quantum Szilard engine". AB - A Comment on the Letter by S. W. Kim et al., Phys. Rev. Lett. 106, 070401 (2011). The authors of the Letter offer a Reply. PMID- 24237571 TI - Kim et al. reply. PMID- 24237572 TI - Comment on "Friction between a viscoelastic body and a rigid surface with random self-affine roughness". AB - A Comment on the Letter by Q. Li, M. Popov, A. Dimaki, A. E. Filippov, S. Kurschner, and V. L. Popov, Phys. Rev. Lett. 111, 034301 (2013). The authors of the Letter offer a Reply. PMID- 24237573 TI - Li et al. reply. PMID- 24237574 TI - Comment on "Percolation transitions are not always sharpened by making networks interdependent". AB - A Comment on the Letter by S. W. Son, P. Grassberger, and M. Paczuski, Phys. Rev. Lett. 107, 195702 (2011). The authors of the Letter offer a Reply. PMID- 24237575 TI - Son, Grassberger, and Paczuski reply. PMID- 24237576 TI - Dense nuclei segmentation based on graph cut and convexity-concavity analysis. AB - With the rapid advancement of 3D confocal imaging technology, more and more 3D cellular images will be available. However, robust and automatic extraction of nuclei shape may be hindered by a highly cluttered environment, as for example, in fly eye tissues. In this paper, we present a novel and efficient nuclei segmentation algorithm based on the combination of graph cut and convex shape assumption. The main characteristic of the algorithm is that it segments nuclei foreground using a graph-cut algorithm with our proposed new initialization method and splits overlapping or touching cell nuclei by simple convexity and concavity analysis. Experimental results show that the proposed algorithm can segment complicated nuclei clumps effectively in our fluorescent fruit fly eye images. Evaluation on a public hand-labelled 2D benchmark demonstrates substantial quantitative improvement over other methods. For example, the proposed method achieves a 3.2 Hausdorff distance decrease and a 1.8 decrease in the merged nuclei error per slice. PMID- 24237577 TI - Pregnancy outcomes in patients with chronic myeloid leukemia treated with imatinib mesylate: short report from a developing country. AB - Treatment of chronic myeloid leukemia (CML) is challenging in patients who want to conceive. We followed 809 patients with CML treated with imatinib mesylate (IM). We observed outcomes in 90 pregnancies from 61 patients (21 females, 40 males) who conceived while on IM. Information was obtained on duration of exposure to IM, pregnancy termination and congenital abnormalities. Hematologic and cytogenetic responses were also recorded. Twenty-eight pregnancies occurred among females, while 62 were reported from male patients. Among female patients, 19 (67.9%) pregnancies were uneventful while six (21.4%) ended in adverse events. Only 12 (57%) females reported their pregnancies. Three (4.4%) adverse events were reported from male patients. Pregnancy is an important part of life in our young patients due to cultural and societal pressures. It is paramount to counsel pregnant patients to switch to drugs with no adverse effect on the developing fetus. However, lack of communication is a major factor preventing physicians from counseling patients about conception. PMID- 24237578 TI - Pleural effusions in patients with Hodgkin lymphoma: clinical predictors and associations with outcome. AB - Pleural effusions are common in Hodgkin lymphoma (HL). However, little is known about their prognostic significance. One hundred and ten patients with HL who presented to the University of Rochester from 1 January 2003 to 12 December 2010 were reviewed. Pleural effusions were evaluated on review of diagnostic-quality computed tomography (CT) scans. Pleural effusions were present in 26/110 patients: 1/7 (14%) stage I, 11/61 (18%) stage II, 3/18 (17%) stage III and 11/24 (46%) stage IV, and 25/91 (27%) patients had mediastinal involvement, 16/38 (42%) patients had extranodal involvement (any) and 5/14 (35%) patients had E lesions (direct extension to extranodal tissue). Unilateral and bilateral pleural effusions were equally prevalent. Survival analysis demonstrated decreased overall survival for patients with pleural effusions of borderline significance for stage I-IV (p = 0.055) but failed to show significance for patients with stage I-III (p = 0.115). Increasing stage, any extranodal involvement and bulky mediastinal disease were each predictive of pleural effusions. The presence of pleural effusion at presentation may be predictive of inferior survival for patients with Hodgkin lymphoma. PMID- 24237579 TI - Rho and Rap guanosine triphosphatase signaling in B cells and chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) cells proliferate predominantly in niches in the lymph nodes, where signaling from the B cell receptor (BCR) and the surrounding microenvironment are critical for disease progression. In addition, leukemic cells traffic constantly from the bloodstream into the lymph nodes, migrate within lymphatic tissues and egress back to the bloodstream. These processes are driven by chemokines and their receptors, and depend on changes in cell migration and integrin-mediated adhesion. Here we describe how Rho and Rap guanosine triphosphatases (GTPases) contribute to both BCR signaling and chemokine receptor signaling, particularly by regulating cytoskeletal dynamics and integrin activity. We propose that new inhibitors of BCR-activated kinases are likely to affect CLL cell trafficking via Rho and Rap GTPases, and that upstream regulators or downstream effectors could be good targets for therapeutic intervention in CLL. PMID- 24237580 TI - Drug development for exceptionally rare metabolic diseases: challenging but not impossible. AB - BACKGROUND: We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). METHODS: All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the 'Orphanet database of Rare diseases'. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). RESULTS: In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). CONCLUSION: For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest. PMID- 24237581 TI - Do preoperative fear avoidance model factors predict outcomes after lumbar disc herniation surgery? A systematic review. AB - BACKGROUND: Lumbar disc herniation (LDH) surgery is usually recommended when conservative treatments fail to manage patients' symptoms. However, many patients undergoing LDH surgery continue to report pain and disability. Preoperative psychological factors have shown to be predictive for postoperative outcomes. Our aim was to systematically review studies that prospectively examined the prognostic value of factors in the Fear Avoidance Model (FAM), including back pain, leg pain, catastrophizing, anxiety, fear-avoidance, depression, physical activity and disability, to predict postoperative outcomes in patients undergoing LDH surgery. METHODS: We performed a systematic literature review of prospective studies that measured any FAM factors preoperatively to predict postoperative outcomes for patients undergoing LDH surgery. Our search databases included PubMed, CINAHL, and PsycINFO. We assessed the quality of each included study using a certain quality assessment list. Degree of agreement between reviewers on quality assessment was examined. Results related to FAM factors in the included studies were summarized. RESULTS: Thirteen prospective studies met our inclusion criteria. Most studies were considered high quality. Heterogeneity was present between the included studies in many aspects. The most common FAM factors examinered were baseline pain, disability and depression. In, general, depression, fear-avoidance behaviors, passive pain coping, and anxiety FAM factors appeared to have negative influence on LDH surgical outcome. Baseline back pain and leg pain appeared to have differing prognostic value on LDH surgical outcomes. CONCLUSIONS: FAM factors seem to influence LDH surgical outcomes. Patients with high levels of depression, anxiety and fear-avoidance behaviors are more likely to have poor outcomes following LDH surgery. Conversely, high levels of leg pain, but not back pain seem to be predictor for favorable LDH surgery outcome. More research is needed to determine the exact role of FAM factors on LDH surgical outcome and the value for screening for these factors. PMID- 24237582 TI - Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon-beta therapy. AB - BACKGROUND AND PURPOSE: Although the first-line disease-modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit-to-risk profile, they are only partially effective for treating relapsing-remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first-line therapy is critical for achieving the best long-term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first-line DMT or a second-line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada. METHODS: A comprehensive literature search for articles published between 1990 and April 2012 was undertaken. RESULTS: This review discusses key clinical and safety data for fingolimod and natalizumab, particularly in the patient subgroups for whom these treatments are approved. Benefit-to-risk profiles, including first-dose cardiovascular effects associated with fingolimod and the risk of progressive multifocal encephalopathy with natalizumab, are discussed. CONCLUSION: A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy. PMID- 24237583 TI - Reliability and Validity of the Persian HIT-6 Questionnaire in Migraine and Tension-type Headache. AB - OBJECTIVE: Headache Impact Test (HIT-6) measures the impact headaches in a 1 month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine. METHODS: Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF 36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's alpha) and test-retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed. RESULTS: Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine. CONCLUSION: Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population. PMID- 24237584 TI - BrpSPL9 (Brassica rapa ssp. pekinensis SPL9) controls the earliness of heading time in Chinese cabbage. AB - The leafy heads of cabbage (Brassica oleracea), Chinese cabbage (Brassica rapa ssp. pekinensis), Brussels sprouts (B. oleracea ssp. gemmifera) and lettuce (Lactuca sativa) comprise extremely incurved leaves that are edible vegetable products. The heading time is important for high quality and yield of these crops. Here, we report that BrpSPL9-2 (B. rapa ssp. pekinensis SQUAMOSA PROMOTER BINDING-LIKE 9-2), a target gene of microRNA brp-miR156, controls the heading time of Chinese cabbage. Quantitative measurements of leaf shapes, sizes, colour and curvature indicated that heading is a late adult phase of vegetative growth. During the vegetative period, miR156 levels gradually decreased from the seedling stage to the heading one, whereas BrpSPL9-2 and BrpSPL15-1 mRNAs increased progressively and reached the highest levels at the heading stage. Overexpression of a mutated miR156-resistant form of BrpSPL9-2 caused the significant earliness of heading, concurrent with shortening of the seedling and rosette stages. By contrast, overexpression of miR156 delayed the folding time, concomitant with prolongation of the seedling and rosette stages. Morphological analysis reveals that the significant earliness of heading in the transgenic plants overexpressing BrpSPL9-2 gene was produced because the juvenile phase was absent and the early adult phase shortened, whereas the significant delay of folding in the transgenic plants overexpressing Brp-MIR156a was due to prolongation of the juvenile and early adult phases. Thus, miR156 and BrpSPL9 genes are potentially important for genetic improvement of earliness of Chinese cabbage and other crops. PMID- 24237585 TI - The Nordic medical birth registers--a potential goldmine for clinical research. AB - The Nordic medical birth registers have long been used for valuable clinical research. Their collection of data for more than four decades offers unusual possibilities for research across generations. At the same time, serum and blotting paper blood samples have been stored from most neonates. Two large cohorts (approximately 100 000 births) in Denmark and Norway have been described by questionnaires, interviews and collection of biological samples (blood, urine and milk teeth), as well as a systematic prospective follow-up of the offspring. National patient registers provide information on preceding, underlying and present health problems of the parents and their offspring. Researchers may, with permission from the national authorities, obtain access to individualized or anonymized data from the registers and tissue-banks. These data allow for multivariate analyses but their usefulness depends on knowledge of the specific registers and biological sample banks and on proper validation of the registers. PMID- 24237586 TI - What do multiple sclerosis patients and their caregivers perceive as unmet needs? AB - BACKGROUND: Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients. METHODS: We evaluated what MS patients and caregivers perceive as unmet needs and compared patients' opinions with caregivers' opinions using a multidimensional questionnaire. The questionnaire was specifically designed for the study, taking into account different aspects of the global care perceived by patients and care givers, such as information about MS, medical treatment and rehabilitation, patients' relationships with medical staff and their psychological and social life. RESULTS: We administered the questionnaire to 497 patients and 206 caregivers. Results showed that the majority of participants were satisfied with medical staff but expressed a desire that staff be more forthcoming with information about MS. As for medical treatment concerns, more patients found there to be useful a multidisciplinary approach than caregivers did. Both required psychological support for patients but patients felt a greater need for it at the time of diagnosis, whereas caregivers felt it was required post-diagnosis. Both reported significant strains on patient relationships at work but no effect on other social interactions. CONCLUSIONS: A better understanding of MS patient needs, starting from the point of view of patients and caregivers, could have a great impact on quality of life and on management of the disease. PMID- 24237588 TI - Theoretical study on the mechanism of stereoselective synthesis of oxazolidinones. AB - Oxazolidinones can be synthesized through an organocatalytic cascade reaction of stable sulfur ylides and nitro-olefins. This process, sequentially catalyzed by thiourea and N,N-dimethylaminopyridine (DMAP), is theoretically studied using density functional theory by the continuum solvation model. It is shown that the rate- and stereoselectivity-determining step is the addition reaction of sulfur ylide to the nitro-olefin with two competing reaction channels. One channel is where the nitro-cyclopropane is generated first and then converted into isoxazoline N-oxide through a DMAP-catalyzed rearrangement. The other channel is the direct generation of the isoxazoline N-oxide intermediate. DMAP plays an important role in the reaction as a nucleophilic catalyst. The mechanism for the important rearrangement reaction proposed by Xiao et al. (J. Am. Chem. Soc. 2008, 130, 6946-6948) is not appropriate as the reaction energy barrier is too high; a 10-step mechanism determined by our theoretical calculations is more feasible as the energy barrier is becoming much less than that by Xiao. It is the first time that the Hofmann rearrangement involved in the cascade organocatalysis is confirmed by theoretical calculations. Our result of the stereoselectivity for the synthesis of oxazolidinones is in good agreement with the experiment. PMID- 24237587 TI - Genome-wide identification of Thellungiella salsuginea microRNAs with putative roles in the salt stress response. AB - BACKGROUND: MicroRNAs are key regulators of plant growth and development with important roles in environmental adaptation. The microRNAs from the halophyte species Thellungiella salsuginea (salt cress), which exhibits extreme salt stress tolerance, remain to be investigated. The sequenced genome of T. salsuginea and the availability of high-throughput sequencing technology enabled us to discover the conserved and novel miRNAs in this plant species. It is interesting to identify the microRNAs from T. salsuginea genome wide and study their roles in salt stress response. RESULTS: In this study, two T. salsuginea small RNA libraries were constructed and sequenced using Solexa technology. We identified 109 miRNAs that had previously been reported in other plant species. A total of 137 novel miRNA candidates were identified, among which the miR* sequence of 26 miRNAs was detected. In addition, 143 and 425 target mRNAs were predicted for the previously identified and Thellungiella-specific miRNAs, respectively. A quarter of these putative targets encode transcription factors. Furthermore, numerous signaling factor encoding genes, defense-related genes, and transporter encoding genes were amongst the identified targets, some of which were shown to be important for salt tolerance. Cleavage sites of seven target genes were validated by 5' RACE, and some of the miRNAs were confirmed by qRT-PCR analysis. The expression levels of 26 known miRNAs in the roots and leaves of plants subjected to NaCl treatment were determined by Affymetrix microarray analysis. The expression of most tested miRNA families was up- or down-regulated upon NaCl treatment. Differential response patterns between the leaves and roots were observed for these miRNAs. CONCLUSIONS: Our results indicated that diverse set of miRNAs of T. salsuginea were responsive to salt stress and could play an important role in the salt stress response. PMID- 24237589 TI - Melancholic and reactive depression: a reappraisal of old categories. AB - BACKGROUND: The dominant diagnostic model of the classification of depression today is unitarian; however, since Kurt Schneider (1920) introduced the concept of endogenous depression and reactive depression, the binary model has still often been used on a clinical basis. Notwithstanding this, to our knowledge, there have been no collective data on how psychiatrists differentiate these two conditions. We therefore conducted a survey to examine how psychiatrists in Japan differentiate patients with major depressive disorder who present mainly with melancholic features and those with reactive features. METHODS: Three case scenarios of melancholic and reactive depression, and one-in-between were prepared. These cases were designed to present with at least 5 symptoms listed in the DSM-IV-TR with severity being mild. We have sent the questionnaires regarding treatment options and diagnosis for those three cases on a 7-point Likert scale (1 = "not appropriate", 4 = "cannot tell", and 7 = "appropriate"). Five hundred and two psychiatrists from over one hundred hospitals and community clinics throughout Japan have participated in this survey. RESULTS: The melancholic case resulted significantly higher than the reactive case on either antidepressants (mean +/- SD: 5.9 +/- 1.2 vs. 3.6 +/- 1.7, p < 0.001), hypnotics (mean +/- SD: 5.5 +/- 1.1 vs. 5.0 +/- 1.3, p < 0.001), and electroconvulsive therapy (mean +/- SD: 1.5 +/- 0.9 vs. 1.2 +/- 0.6, p < 0.001). On the other hand, the reactive case resulted in significantly higher scores compared to the melancholic case and the one- in-between cases in regards to psychotherapy (mean +/- SD: 4.9 +/- 1.4 vs. 4.3 +/- 1.4 vs. 4.7 +/- 1.5, p < 0.001, respectively). Scores for informing patients that they suffered from "depression" were significantly higher in the melancholic case, compared to the reactive case (mean +/- SD: 4.7 +/- 1.7 vs. 2.2 +/- 1.4, p < 0.001). CONCLUSIONS: Japanese psychiatrists distinguish between major depressive disorder with melancholic and reactive features, and thus choose different treatment strategies regarding pharmacological treatment and psychotherapy. PMID- 24237590 TI - Unipolar voltage abnormality is associated with greater left ventricular dysfunction in ischemic cardiomyopathy. AB - INTRODUCTION: Following myocardial infarction (MI), left ventricular function is determined by cardiac remodeling occurring in both infarcted and noninfarcted myocardium (NIM). Unipolar voltage mapping may detect remodeling changes in NIM that are associated with the left ventricular ejection fraction (LVEF). We aimed to identify (1) unipolar voltage characteristics in patients with chronic MI, and (2) association of voltage abnormalities with degree of left ventricular dysfunction (LVD). METHODS AND RESULTS: Two groups of patients with ischemic cardiomyopathy (ICM) who underwent LV endocardial mapping during catheter ablation for ventricular tachycardia (VT) between January 2010 and December 2012 were studied. The first group (19 males) had mild to moderate LVD (M-LVD, LVEF >35%) and was matched for age, sex, infarction size, and infarction location with 10 males who had severe LVD (S-LVD, LVEF <35%). Both bipolar and unipolar endocardial abnormal voltage areas were measured and compared between groups. Abnormal bipolar area was comparable in both groups (30 +/- 8% in the S-LVD group vs 28 +/- 8% in the M-LVD group; P = 0.5). Total abnormal unipolar voltage area was significantly larger in the S-LVD group (57 +/- 14% vs 43 +/- 13%; P = 0.02). The abnormal unipolar voltage area within the normal bipolar voltage area was greater in the S-LVD group (26 +/- 11% vs 15 +/- 16%; P = 0.03). In receiver operating characteristic curve analysis, an 18.0% cut-off value for abnormal unipolar area within NIM identified severe LVD, with 90% sensitivity and 79% specificity (area under the curve 0.821). CONCLUSIONS: Patients with ICM and severe LVD have larger areas of unipolar voltage abnormality in the noninfarcted tissue than patients with M-LVD. PMID- 24237591 TI - Establishment of transgenic silkworms expressing GAL4 specifically in the haemocyte oenocytoid cells. AB - Insect haemocytes play significant roles in innate immunity. The silkworm, a lepidopteran species, is often selected as the model for studies into the functions of haemocytes in immunity; however, our understanding of the role of haemocytes remains limited because the lack of haemocyte promoters for transgene expression makes genetic manipulations difficult. In the present study, we aimed to establish transgenic silkworm strains expressing GAL4 in their haemocytes. First, we identified three genes with strong expression in haemocytes, namely, lp44, Haemocyte Protease 1 (HP1) and hemocytin. Transgenic silkworms expressing GAL4 under the control of the putative promoters of these genes were then established and expression was examined. Although GAL4 expression was not detected in haemocytes of HP1-GAL4 or hemocytin-GAL4 strains, lp44-GAL4 exhibited a high level of GAL4 expression, particularly in oenocytoids. GAL4 expression was also detected in the midgut but in no other tissues, indicating that GAL4 expression in this strain is mostly oenocytoid-specific. Thus, we have identified a promoter that enables oenocytoid expression of genes of interest. Additionally, the lp44-GAL4 strain could also be used for other types of research, such as the functional analysis of genes in oenocytoids, which would facilitate advances in our understanding of insect immunity. PMID- 24237592 TI - Laser therapy of onychomycosis. AB - Since 2010 the FDA has approved laser systems as capable of producing a "temporary increase in clear nails" in patients with onychomycosis. Fungal eradication is probably mediated by heat in infrared laser systems; their efficacy has been confirmed thermographically, histologically and in electron microscopy. Another approach to decontaminate the nail organ is to disrupt fungi and spores by q-switched pulse applications. Recently specific combinations of wavelengths have been tested for their ability to disrupt the mitochondrial transmembrane potential at physiological temperatures by generating ATP and ROS. While clinically extremely high clearance rates of approximately 87.5-95.8 % have been reported, in-vitro investigations have failed to confirm the clearance. The variety of systems and advised parameters hampers a systematic evaluation. Recommendations for safe and practical treatment protocols, informed consent items, and combination with conventional treatment options are all areas of active work. Currently there is a lack of data concerning the long-term efficacy of laser therapy of onychomycosis; certified treatment protocols are needed. PMID- 24237593 TI - Si-RNA mediated knockdown of CELF1 gene suppressed the proliferation of human lung cancer cells. AB - BACKGROUND: Lung cancer is the leading cause of cancer-related death in the world, with metastasis as the main reason for the mortality. CELF1 is an RNA binding protein controlling the post-transcriptional regulation of genes related to cell survival. As yet, there is little knowledge of CELF1 expression and biological function in lung cancer. This study investigated the expression levels of CELF1 in lung cancer tissues and the biological function of CELF1 in lung cancer cells. METHODS: CELF1 mRNA expression was determined in lung cancer and normal tissues, and the relationship between the expression level of CELF1 and clinicopathological parameters was evaluated. The biological function of CELF1 in A549 and H1299 lung cancer cell lines growth was examined. RESULTS: The expression of CELF1 was higher in human lung cancer tissues compared with the normal lung tissue. Lentiviral-mediated transfection of CELF1 siRNA effectively silenced the expression of CELF1 in both A549 and H1299 cells. Moreover, CELF1 knockdown markedly reduced the survival rate of lung cancer cells. Colony formation assays revealed a reduction in the number and size of lung cancer cell colonies from CELF1 knockdown. CONCLUSION: These results indicated that CELF1 may have significant roles in the progression of lung cancer, and suggested that siRNA mediated silencing of CELF1 could be an effective tool in lung cancer treatment. PMID- 24237594 TI - Differentiation between sediment and hypolimnion methanogen communities in humic lakes. AB - The traditional view of carbon cycling within the pelagic zone of freshwater lakes has consisted of methane production within the anoxic sediment, followed by diffusive flux and ebullition through the water column. Methanogenic archaea have been shown to be present within the water columns of freshwater lakes; however, little is known about whether these methanogenic communities are distinct from those in the sediment or how these communities change over space and time. We used the methanogen-specific phylogenetic marker mcrA to perform a 3-year study focusing on the community structure of methanogens within the sediment and anoxic hypolimnion water layer of five humic lakes in WI, USA. The hypolimnion and sediment communities were distinct in composition, richness and phylogenetic diversity. Hypolimnion communities displayed a temporally stable biogeographical pattern among lakes, which was driven by both lake-specific environmental variables and barriers to dispersal. We conclude that the hypolimnion comprised communities of methanogens that are distinct from those in the sediment, differentiated among lakes, and likely have unique ecological roles and evolutionary trajectories in these anaerobic environments. PMID- 24237595 TI - Role of flavohaemoprotein Hmp and nitrate reductase NarGHJI of Corynebacterium glutamicum for coping with nitrite and nitrosative stress. AB - The influence of nitrate and nitrite on growth of Corynebacterium glutamicum under aerobic conditions in shake flasks was analysed. When dissolved oxygen became limiting at higher cell densities, nitrate was reduced almost stoichiometrically to nitrite by nitrate reductase (NarGHJI). The nitrite concentration also declined slowly, presumably as a result of several reactions including reduction to nitric oxide by a side-activity of nitrate reductase. The flavohaemoglobin gene hmp was most strongly upregulated (19-fold) in the presence of nitrite. Hmp is known to catalyse the oxygen-dependent oxidation of nitric oxide to nitrate and, in the absence of oxygen, with a much lower rate the reduction of nitric oxide to nitrous oxide. A Deltahmp mutant showed strong growth defects under aerobic conditions in the presence of nitrate, nitrite and the NO-donating reagent sodium nitroprusside, but also under anaerobic nitrate respiring conditions. Therefore, Hmp is likely to be responsible for nitric oxide conversion to either nitrate or nitrous oxide in C. glutamicum. The results suggest that a cyclic nitrate-nitrite conversion takes place in C. glutamicum under microaerobic conditions. PMID- 24237596 TI - Biomarkers for intracellular pathogens: establishing tools as vaccine and therapeutic endpoints for visceral leishmaniasis. AB - Visceral leishmaniasis in South Asia is a serious disease affecting children and adults. Acute visceral leishmaniasis develops in only a fraction of those infected individuals, the majority being asymptomatic with the potential to transmit infection and develop disease. We followed 56 individuals characterized as being asymptomatic by seropositivity with rk39 rapid diagnostic test in a hyperendemic district of Bangladesh to define the utility of Leishmania-specific antibodies and DNA in identifying infection. At baseline, 54 of the individuals were seropositive with one or more quantitative antibody assays and antibody levels persisted at follow up. Most seropositive individuals (47/54) tested positive by quantitative PCR at baseline, but only 16 tested positive at follow up. The discrepancies among the different tests may shed light on the dynamics of asymptomatic infections of Leishmania donovani, as well as underscore the need for standard diagnostic tools for active surveillance as well as assessing the effectiveness of prophylactic and therapeutic interventions. PMID- 24237597 TI - Reconsidering policy of casualty evacuation in a remote mass-casualty incident. AB - OBJECTIVES: Inappropriate distribution of casualties in mass-casualty incidents (MCIs) may overwhelm hospitals. This study aimed to review the consequences of evacuating casualties from a bus accident to a single peripheral hospital and lessons learned regarding policy of casualty evacuation. METHODS: Medical records of all casualties relating to evacuation times, injury severity, diagnoses, treatments, resources utilized and outcomes were independently reviewed by two senior trauma surgeons. In addition, four senior trauma surgeons reviewed impact of treatment provided on patient outcomes. They reviewed the times for the primary and secondary evacuation, injury severity, diagnoses, surgical treatments, resources utilized, and the final outcomes of the patients at the point of discharge from the tertiary care hospital. RESULTS: Thirty-one survivors were transferred to the closest local hospital; four died en route to hospital or within 30 minutes of arrival. Twenty-seven casualties were evacuated by air from the local hospital within 2.5 to 6.15 hours to Level I and II hospitals. Undertriage of 15% and overtriage of seven percent were noted. Four casualties did not receive treatment that might have improved their condition at the local hospital. CONCLUSIONS: In MCIs occurring in remote areas, policy makers should consider revising the current evacuation plan so that only immediate unstable casualties should be transferred to the closest primary hospital. On site Advanced Life Support (ALS) should be administered to non-severe casualties until they can be evacuated directly to tertiary care hospitals. First responders must be trained to provide ALS to non-severe casualties until evacuation resources are available. PMID- 24237598 TI - NK cells from an AML patient have recovered in remission and reached comparable cytolytic activity to that of a healthy monozygotic twin mediated by the single chain triplebody SPM-2. AB - BACKGROUND: The capacity of patient's Natural Killer cells (NKs) to be activated for cytolysis is an important prerequisite for the success of antibody-derived agents such as single-chain triplebodies (triplebodies) in cancer therapy. NKs recovered from AML patients at diagnosis are often found to be reduced in peripheral blood titers and cytolytic activity. Here, we had the unique opportunity to compare blood titers and cytolytic function of NKs from an AML patient with those of a healthy monozygotic twin. The sibling's NKs were compared with the patient's drawn either at diagnosis or in remission after chemotherapy. The cytolytic activities of NKs from these different sources for the patient's autologous AML blasts and other leukemic target cells in conjunction with triplebody SPM-2, targeting the surface antigens CD33 and CD123 on the AML cells, were compared. METHODS: Patient NKs drawn at diagnosis were compared to NKs drawn in remission after chemotherapy and a sibling's NKs, all prepared from PBMCs by immunomagnetic beads (MACS). Redirected lysis (RDL) assays using SPM-2 and antibody-dependent cellular cytotoxicity (ADCC) assays using the therapeutic antibody RituximabTM were performed with the enriched NKs. In addition, MACS sorted NKs were analyzed for NK cell activating receptors (NCRs) by flow cytometry, and the release of TNF-alpha and IFN-gamma from blood samples of both siblings after the addition of the triplebody were measured in ELISA-assays. RESULTS: Patient NKs isolated from peripheral blood drawn in remission produced comparable lysis as NKs from the healthy twin against the patient's autologous bone marrow (BM) blasts, mediated by SPM-2. The NCR receptor expression profiles on NKs from patient and twin were similar, but NK cell titers in peripheral blood were lower for samples drawn at diagnosis than in remission. CONCLUSIONS: Peripheral blood NK titers and ex vivo cytolytic activities mediated by triplebody SPM-2 were comparable for cells drawn from an AML patient in remission and a healthy twin. If these results can be generalized, then NKs from AML patients in remission are sufficient in numbers and cytolytic activity to make triplebodies promising new agents for the treatment of AML. PMID- 24237599 TI - Dermoscopic nevus patterns in skin of colour: a prospective, cross-sectional, morphological study in individuals with skin type V and VI. AB - BACKGROUND: Most of the knowledge on the prevailing dermoscopic patterns of acquired melanocytic nevi (AMV) is based on studies in Caucasians, while little research focuses on the dermoscopic variability in nevi in skin of colour. OBJECTIVE: To analyse the prevalent dermoscopic nevus patterns in subjects with a skin type (ST) V and VI. METHODS: Prospective, cross-sectional, morphological study was conducted in six clinics with enrolment of consecutive individuals with a ST V or VI. Digital dermoscopic images of selected representative AMN were assessed for dermoscopic colours, morphological patterns and pigment distribution. RESULTS: Analysis of 300 nevi from subjects with ST V and VI revealed significant differences in the nevus pattern between these two groups. The majority of nevi in ST V revealed a reticular pattern, whereas persons with ST VI more frequently exhibited a structureless pattern. Black, blue and grey were more frequent in ST VI, whereas the vast majority of nevi in ST V individuals showed dark brown colour. CONCLUSIONS: Our study provides new insights into the nevus pattern in individuals with a dark pigmentary trait, which may aid the diagnosis and management of nevi in this patients group. PMID- 24237600 TI - Delayed migration of hyaluronic acid fillers: a new complication? PMID- 24237601 TI - Clinical characterization of epilepsy of unknown cause in cats. AB - BACKGROUND: The diagnosis of feline epilepsy of unknown cause (EUC) requires a thorough diagnostic evaluation, otherwise the prevalence of EUC could be overestimated. HYPOTHESIS: Feline EUC is a clinically defined disease entity, which differs from feline hippocampal necrosis by the absence of magnetic resonance imaging (MRI) signal alteration of the hippocampus. The objectives of this study were (1) to evaluate the prevalence of EUC in a hospital population of cats by applying well-defined inclusion criteria, and (2) to describe the clinical course of EUC. ANIMALS: Eighty-one cats with recurrent seizures. METHODS: Retrospective study--medical records were reviewed for cats presented for evaluation of recurrent seizures (2005-2010). Inclusion criteria were a defined diagnosis based on laboratory data, and either MRI or histopathology. Final outcome was confirmed by telephone interview with the owner. Magnetic resonance images were reviewed to evaluate hippocampal morphology and signal alterations. RESULTS: Epilepsy of unknown cause was diagnosed in 22% of cats with epilepsy. Physical, neurologic, and laboratory examinations, and either 1.5 T MRI and cerebrospinal fluid analysis or postmortem examination failed to identify an underlying cause. Cats with EUC had a higher survival rate (P < .05) and seizure remission occurred frequently (44.4%). CONCLUSION AND CLINICAL IMPORTANCE: A detailed clinical evaluation and diagnostic imaging with MRI is recommended in any cat with recurrent seizures. The prognosis of cats with normal MRI findings and a clinical diagnosis of EUC are good. Standardized imaging guidelines should be established to assess the hippocampus in cats. PMID- 24237602 TI - Salivary cortisol levels, but not salivary alpha-amylase levels, are elevated in patients with rheumatoid arthritis irrespective of depression. AB - OBJECTIVES: Stress is recognized as an important factor in the etiology of rheumatoid arthritis (RA). Therefore, we explored multiple aspects of stress in RA patients. METHODS: Salivary cortisol and alpha-amylase levels were measured as markers of the hypothalamic-pituitary-adrenal axis activity and sympatho adrenomedullary system activity, respectively. Depression was assessed by the Beck Depression Inventory (BDI) and short-term analysis of the heart rate variability (HRV) was performed to evaluate the autonomic nervous system. RESULTS: The salivary cortisol levels of the RA patients were significantly higher than those of the normal controls (NC; 0.12 +/- 0.162 MUg/dL vs. 0.068 +/- 0.052 MUg/dL, P = 0.006). There was no difference in salivary alpha-amylase levels between the RA and the NC. The BDI levels of the RA patients were significantly higher than the NC (13.7 +/- 8.9 vs. 6.4 +/- 6.9, P < 0.001). Depression was more prevalent in RA patients than in the NC. The salivary cortisol levels were still significantly higher in the RA than the NC after controlling BDI by logistic regression analysis (P = 0.002). There was no significant difference in the HRV of RA patients and the NC. The evaluation of relationship between stress measures and disease activity markers of RA revealed that only BDI was positively correlated with the visual analogue pain scale. CONCLUSION: Salivary cortisol levels and the BDI of RA patients were higher than those of the NC, and elevated salivary cortisol levels were independent of depression. However, the level of stress may not be correlated with disease activity in RA. PMID- 24237603 TI - Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: a long-term follow-up study. AB - BACKGROUND AND PURPOSE: Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI). METHODS: All subjects with head trauma (n = 827) brought to the emergency room at Oulu University Hospital during 1999 were identified and followed up until death or the end of 2009. The National Hospital Discharge Register and hospital charts were used to identify TBIs during the follow-up and Kaplan-Meier curves and the Cox proportional hazards model were used to characterize predictors of TBI. RESULTS: During the total follow-up of 7386 person-years, 52/827 subjects sustained a new head trauma with TBI and the risk of TBI was significantly (P = 0.005) higher amongst subjects who had been under the influence of alcohol at the time of the index trauma in 1999. New TBI occurred under the influence of alcohol in 30/52 cases (57.7%). An alcohol-related index trauma [adjusted hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.38-4.56, P < 0.01] and history of TBI (HR 3.39, 95% CI 1.32-8.72, P < 0.05) were independent risk factors for subsequent TBI after adjustment for sex and age. A history of harmful drinking was also a significant risk factor (adjusted HR 10.37, 95% CI 5.53-19.43, P < 0.001). In the subset of 396 patients having an index head trauma without TBI, this being alcohol related was also a significant risk factor for subsequent TBI after adjustment for sex, age and history of TBI (HR 3.54, 95% CI 1.36-9.18, P = 0.009). CONCLUSIONS: Even head trauma without TBI under the influence of alcohol implies an elevated risk of subsequent TBI. A brief intervention to reduce hazardous drinking is needed to prevent TBI. PMID- 24237604 TI - A comparative study on the anti-inflammatory effects of single oral doses of naproxen and its hydrogen sulfide (H2S)-releasing derivative ATB-346 in rats with carrageenan-induced synovitis. AB - BACKGROUND: Non-steroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed agents for arthritic patients, although gastric effects limit their long-term use. Considering the reported gastric safety of hydrogen sulfide (H2S) releasing NSAIDs, in addition to the anti-inflammatory effects of H2S administration to rats with synovitis, we decided to evaluate the effects of the H2S-releasing naproxen derivative ATB-346 in this animal model. METHODS: Male Wistar rats were anesthetized with inhalatory halothane and pre-treated with equimolar oral doses of either naproxen (0.3, 1, 3 or 10 mg/kg) or ATB-346 (0.48, 1.6, 4.8, or 16 mg/kg) 30 min before the i.art. injection of 7.5 mg of carrageenan (CGN) into the right knee joint cavity. Joint swelling and pain score were assessed after 1, 3 and 5 h, and tactile allodynia after 2 and 4 h. After the last measurement, the joint cavity lavages were performed for counting of the recruited leukocytes. The drugs (at the highest doses) were also tested for their gastric effects by evaluating macroscopical damage score and neutrophil recruitment (measured as myeloperoxidase - MPO activity) in the stomachs 5 h after administration of the drugs. In addition, the serum naproxen pharmacokinetic profiles of both compounds, administered at the highest equimolar doses, were obtained during the first 6 h after dosing. RESULTS: At the two highest tested doses, both naproxen and ATB-346 reduced edema and pain score (measured 3 and 5 h after CGN; P < 0.001). Tactile allodynia was similarly inhibited by ~45% 4 h after CGN by both naproxen (at 1, 3 and 10 mg/kg) and ATB 346 (at 1.6 and 4.8 mg/kg; P < 0.001), as well as leukocyte infiltration. Naproxen (but not ATB-346) induced significant gastric damage and, despite the increased gastric MPO activity by ~130% in the naproxen-, but not in the ATB-346 treated rats, this effect was of no statistical significance. CONCLUSION: The presence of a H2S-releasing moiety in the ATB-346 structure does not impair the antiinflammatory activity of the parent compound in rats with CGN-induced synovitis. In addition, released H2S may account for the absence of deleterious gastric effects, thus making of ATB-346 a potentially useful therapeutic alternative to traditional naproxen for treatment of patients with arthritis. PMID- 24237605 TI - Funding innovation for treatment for rare diseases: adopting a cost-based yardstick approach. AB - BACKGROUND: Manufacturers justify the high prices for orphan drugs on the basis that the associated R&D costs must be spread over few patients. The proliferation of these drugs in the last three decades, combined with high prices commonly in excess of $100,000 per patient per year are placing a substantial strain on the budgets of drug plans in many countries. Do insurers spend a growing portion of their budgets on small patient populations, or leave vulnerable patients without coverage for valuable treatments? We suggest that a third option is present in the form of a cost-based regulatory mechanism. METHODS: This article explores the use of a cost-based price control mechanism for orphan drugs, adapted from the standard models applied in utilities regulation. RESULTS AND CONCLUSIONS: A rate of-return style model, employing yardsticked cost allocations and a modified two stage rate of return calculation could be effective in setting a new standard for orphan drugs pricing. This type of cost-based pricing would limit the costs faced by insurers while continuing to provide an efficient incentive for new drug development. PMID- 24237606 TI - Inducible expression of a fusion gene encoding two proteinase inhibitors leads to insect and pathogen resistance in transgenic rice. AB - Plant proteinase inhibitors (PIs) are considered as candidates for increased insect resistance in transgenic plants. Insect adaptation to PI ingestion might, however, compromise the benefits received by transgenic expression of PIs. In this study, the maize proteinase inhibitor (MPI), an inhibitor of insect serine proteinases, and the potato carboxypeptidase inhibitor (PCI) were fused into a single open reading frame and introduced into rice plants. The two PIs were linked using either the processing site of the Bacillus thuringiensis Cry1B precursor protein or the 2A sequence from the foot-and-mouth disease virus (FMDV). Expression of each fusion gene was driven by the wound- and pathogen inducible mpi promoter. The mpi-pci fusion gene was stably inherited for at least three generations with no penalty on plant phenotype. An important reduction in larval weight of Chilo suppressalis fed on mpi-pci rice, compared with larvae fed on wild-type plants, was observed. Expression of the mpi-pci fusion gene confers resistance to C. suppressalis (striped stem borer), one of the most important insect pest of rice. The mpi-pci expression systems described may represent a suitable strategy for insect pest control, better than strategies based on the use of single PI genes, by preventing insect adaptive responses. The rice plants expressing the mpi-pci fusion gene also showed enhanced resistance to infection by the fungus Magnaporthe oryzae, the causal agent of the rice blast disease. Our results illustrate the usefulness of the inducible expression of the mpi-pci fusion gene for dual resistance against insects and pathogens in rice plants. PMID- 24237607 TI - Acute tryptophan depletion - converging evidence for decreasing central nervous serotonin synthesis in rodents and humans. PMID- 24237609 TI - Sparganosis presenting as a mammographic abnormality. PMID- 24237608 TI - Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. AB - BACKGROUND: Recently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans. METHODS: One hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2(-DeltaDeltact) method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated. RESULTS: Circulating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively. CONCLUSIONS: These data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans. PMID- 24237610 TI - EP42675, a synthetic parenteral dual-action anticoagulant: pharmacokinetics, pharmacodynamics, and absence of interactions with antiplatelet drugs. AB - BACKGROUND: EP42675 is a first-in-class, synthetic, parenteral, anticoagulant combining in a single molecule a direct thrombin inhibitor and an indirect factor Xa(FXa) inhibitor. OBJECTIVES: To investigate the safety, pharmacokinetics, and pharmacodynamics of EP42675 and its interaction with aspirin, clopidogrel, and unfractionated heparin (UFH). SUBJECTS AND METHODS: In study 1, healthy male subjects were administered intravenously single-ascending doses (1-10 mg) of EP42675 or placebo. In study 2, healthy male subjects were administered intravenously a single dose of 5 mg EP42675 on day 1 followed by oral administration of aspirin (100 mg) and clopidogrel (75 mg) once daily from day 8 to 21. On day 15, a second dose of 5 mg EP42675 was administered, and subjects were then randomized to receive a single dose of UFH (30 or 60 IU kg(-1) ) or placebo. RESULTS AND CONCLUSIONS: Mild bleedings were the only drug-related adverse events. EP42675 pharmacokinetics were dose-proportional and characterized by a low clearance, a small volume of distribution, a long terminal half-life. EP42675 pharmacodynamics were characterized by a long-lasting, dose-dependent increase in activated clotting time, ecarin clotting time, thrombin time, anti FXa activity, activated partial thromboplastin time, prothrombin time, and a decrease in endogenous thrombin potential, measured by a thrombin generation test. Dose-dependent additive effects were seen with UFH on coagulation tests. EP42675 had no additive effect on the inhibition of platelet aggregation induced by aspirin and clopidogrel. These results warrant further clinical development of this new class of anticoagulant. PMID- 24237611 TI - Tumor-dependent increase of serum amino acid levels in breast cancer patients has diagnostic potential and correlates with molecular tumor subtypes. AB - BACKGROUND: Malignancies induce changes in the levels of serum amino acids (AA), which may offer diagnostic potential. Furthermore, changes in AA levels are associated with immune cell function. In this study, serum AA levels were studied in breast cancer patients versus patients with benign breast lesions. METHODS: In a prospective study, serum levels of 15 AA were measured by high performance liquid chromatography before and after surgery in 41 breast cancer patients (BrCA) and nine patients with benign breast lesions (healthy donors, HD). Results were analyzed in relation to clinical tumor data and tested against immunological flow cytometry data. Principal component analysis was performed and the accuracy of AA levels as a potential diagnostic tool was tested. RESULTS: Pre- but not postoperative serum AA levels were increased in BrCA in eight out of 15 AA compared with HD. Serum AA levels were highest in the most aggressive (basal like) as compared with the least aggressive tumor subtype (luminal A). A principal component (PC1) of all measured AA correlated with a mainly pro inflammatory immune profile, while a second one (PC2, selectively considering AA preoperatively differing between HD and BrCA) could predict health state with an area under the curve of 0.870. CONCLUSIONS: Breast cancer shows a tumor-dependent impact on serum AA levels, which varies with intrinsic tumor subtypes and is associated with a pro-inflammatory state. Serum AA levels need further evaluation as a potential diagnostic tool. PMID- 24237612 TI - Acute safety and efficacy of a novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation. AB - INTRODUCTION: "Single shot" ablation devices to treat symptomatic atrial fibrillation have been engineered over the last years. Safety and efficacy also includes subclinical complications only detected with esophageal endoscopy or cerebral MRI in asymptomatic patients. We studied the acute efficacy and safety profile of a novel multipolar irrigated RF ablation catheter (nMARQTM). METHODS AND RESULTS: Forty-three patients underwent pulmonary vein isolation (PVI) using the novel ablation device. Patient baseline and procedural characteristics were documented. Efficacy of PVI was identified using only the nMARQTM catheter. All patients underwent postablation endoscopic evaluation of the esophagus to document thermal damage and cerebral MRI (diffusion weight imaging, attenuated diffusion coefficient-map) to document incidence and number of silent cerebral lesions (SCL). Effective PVI was achieved in 98% of targeted PVs in a mean procedure time of 133 minutes. A mean of 4.8, 60-second RF applications, per PV was needed for effective PVI. No clinical procedure-associated complications were noted. Esophageal temperature increase >40.5 degrees C was noted in 22 (51%) patients and 14 of these had thermal esophageal lesions on endoscopic evaluation. A total of 26 SCLs were noted in 14 patients (33%; 1.9/patient; mean diameter of 2.3 mm, 88% of lesions were <=3 mm). CONCLUSIONS: PVI using the novel irrigated RF multipolar ablation device (nMARQTM) appears to be acutely effective. No clinical complications were identified. A high incidence of SCL (33%) and thermal esophageal lesions (33%) bears caution and further studies on long-term efficacy and safety are needed. PMID- 24237613 TI - Identification and characterization of the three homeologues of a new sucrose transporter in hexaploid wheat (Triticum aestivum L.). AB - BACKGROUND: Sucrose transporters (SUTs) play important roles in regulating the translocation of assimilates from source to sink tissues. Identification and characterization of new SUTs in economically important crops such as wheat provide insights into their role in determining seed yield. To date, however, only one SUT of wheat has been reported and functionally characterized. The present study reports the isolation and characterization of a new SUT, designated as TaSUT2, and its homeologues (TaSUT2A, TaSUT2B and TaSUT2D) in hexaploid wheat (Triticum aestivum L.). RESULTS: TaSUT2A and TaSUT2B genes each encode a protein with 506 amino acids, whereas TaSUT2D encodes a protein of 508 amino acids. The molecular mass of these proteins is predicted to be ~ 54 kDA. Topological analysis of the amino acid sequences of the three homeologues revealed that they contain 12 transmembrane spanning helices, which are described as distinct characteristic features of glycoside-pentoside-hexuronide cation symporter family that includes all known plant SUTs, and a histidine residue that appears to be localized at and associated conformationally with the sucrose binding site. Yeast SUSY7/ura3 strain cells transformed with TaSUT2A, TaSUT2B and TaSUT2D were able to uptake sucrose and grow on a medium containing sucrose as a sole source of carbon; however, our subcellular localization study with plant cells revealed that TaSUT2 is localized to the tonoplast. The expression of TaSUT2 was detected in the source, including flag leaf blade, flag leaf sheath, peduncle, glumes, palea and lemma, and sink (seed) tissues. The relative contributions of the three genomes of wheat to the total expression of TaSUT2 appear to differ with tissues and developmental stages. At the cellular level, TaSUT2 is expressed mainly in the vein of developing seeds and subepidermal mesophyll cells of the leaf blade. CONCLUSION: This study demonstrated that TaSUT2 is a new wheat SUT protein. Given that TaSUT2 is localized to the tonoplast and sucrose is temporarily stored in the vacuoles of both source and sink tissues, our data imply that TaSUT2 is involved in the intracellular partitioning of sucrose, particularly between the vacuole and cytoplasm. PMID- 24237614 TI - EBR1 genomic expansion and its role in virulence of Fusarium species. AB - Genome sequencing of Fusarium oxysporum revealed that pathogenic forms of this fungus harbour supernumerary chromosomes with a wide variety of genes, many of which likely encode traits required for pathogenicity or niche specialization. Specific transcription factor gene families are expanded on these chromosomes including the EBR1 family (Enhanced Branching). The significance of the EBR1 family expansion on supernumerary chromosomes and whether EBR1 paralogues are functional is currently unknown. EBR1 is found as a single copy in F.graminearum and other fungi but as multiple paralogues in pathogenic F.oxysporum strains. These paralogues exhibit sequence and copy number variation among different host specific strains and even between more closely related strains. Relative expression of the EBR1 paralogues depends on growth conditions and on the presence of the single EBR1 gene in the core genome. Deletion of EBR1 in the core genome in different F.oxysporum strains resulted in impaired growth, reduced pathogenicity and slightly reduced biocontrol capacities. To identify genes regulated by EBR1, the transcriptomes of wild-type and Deltaebr1 strains were compared for both F.oxysporum and F.graminearum. These studies showed that in both species, EBR1 regulates genes involved in general metabolism as well as virulence. PMID- 24237616 TI - Combined effects of resource heterogeneity and simulated herbivory on plasticity of clonal integration in a rhizomatous perennial herb. AB - Previous lines of investigation assuming potential advantage of clonal integration generally have neglected its plasticity in complex heterogeneous environments. Clonal plants adaptively respond to abiotic heterogeneity (patchy resource distribution) and herbivory-induced heterogeneity (within-clone heterogeneity in ramet performance), but to date little is known about how resource heterogeneity and simulated herbivory jointly affect the overall performance of clones. Partial damage within a clone caused by herbivory might create herbivory-induced heterogeneity in a resource-homogeneous environment, and might also decrease or increase the extent of heterogeneity under resource heterogeneous conditions. We conducted a greenhouse experiment in which target ramets of Leymus chinensis segments within homogeneous or heterogeneous nutrient treatments were subject to clipping (0% or 75% shoot removal). In homogeneous environments with high (9:9) nutrient availability, ramet biomass of L. chinensis with intact or severed rhizomes is 0.70 or 0.69 g. Conversely, target-ramet biomass with intact rhizomes is obviously lower than that of the severed target ramets in the homogeneous environments with medium (5:5) and low (1:1) nutrient availability. High resource availability and the presence of herbivory can alleviate negative effects of rhizome connection under homogeneous conditions, by providing copious resource or creating herbivory-induced heterogeneity respectively. Herbivory tolerance of clonal fragments with connected rhizomes was higher than that of fragments with severed rhizomes under heterogeneous conditions. These findings confirmed the unconditional advantage of clonal integration on reproduction under the combined influence of resource heterogeneity and simulated herbivory. Moreover, our results made clear the synergistically interactive effects of resource heterogeneity and simulated herbivory on costs and benefits of clonal integration. This will undoubtedly advance our understanding on the plasticity of clonal integration under complex environmental conditions. PMID- 24237615 TI - No evidence for zoonotic transmission of H3N8 canine influenza virus among US adults occupationally exposed to dogs. AB - OBJECTIVES: The zoonotic potential of H3N8 canine influenza virus (CIV) has not been previously examined; yet considering the popularity of dogs as a companion animal and the zoonotic capabilities of other influenza viruses, the public health implications are great. This study aimed to determine the seroprevalence of antibodies against CIV among a US cohort. DESIGN: A cross-sectional seroepidemiological study was conducted between 2007 and 2010. SETTING: Recruitments primarily occurred in Iowa and Florida. Participants were enrolled at dog shows, or at their home or place of employment. SAMPLE: Three hundred and four adults occupationally exposed to dogs and 101 non-canine-exposed participants completed a questionnaire and provided a blood sample. MAIN OUTCOME MEASURES: Microneutralization and neuraminidase inhibition assays were performed to detect human sera antibodies against A/Canine/Iowa/13628/2005(H3N8). An enzyme linked lectin assay (ELLA) was adapted to detect antibodies against a recombinant N8 neuraminidase protein from A/Equine/Pennsylvania/1/2007(H3N8). RESULTS: For all assays, no significant difference in detectable antibodies was observed when comparing the canine-exposed subjects to the non-canine-exposed subjects. CONCLUSION: While these results do not provide evidence for cross-species CIV transmission, influenza is predictably unpredictable. People frequently exposed to ill dogs should continually be monitored for novel zoonotic CIV infections. PMID- 24237618 TI - Irregular gout. PMID- 24237617 TI - Impact of a mobile phone and web program on symptom and functional outcomes for people with mild-to-moderate depression, anxiety and stress: a randomised controlled trial. AB - BACKGROUND: Mobile phone-based psychological interventions enable real time self monitoring and self-management, and large-scale dissemination. However, few studies have focussed on mild-to-moderate symptoms where public health need is greatest, and none have targeted work and social functioning. This study reports outcomes of a CONSORT-compliant randomised controlled trial (RCT) to evaluate the efficacy of myCompass, a self-guided psychological treatment delivered via mobile phone and computer, designed to reduce mild-to-moderate depression, anxiety and stress, and improve work and social functioning. METHOD: Community-based volunteers with mild-to-moderate depression, anxiety and/or stress (N = 720) were randomly assigned to the myCompass program, an attention control intervention, or to a waitlist condition for seven weeks. The interventions were fully automated, without any human input or guidance. Participants' symptoms and functioning were assessed at baseline, post-intervention and 3-month follow-up, using the Depression, Anxiety and Stress Scale and the Work and Social Adjustment Scale. RESULTS: Retention rates at post-intervention and follow-up for the study sample were 72.1% (n = 449) and 48.6% (n = 350) respectively. The myCompass group showed significantly greater improvement in symptoms of depression, anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase (between-group effect sizes ranged from d = .22 to d = .55 based on the observed means). Symptom scores remained at near normal levels at 3-month follow-up. Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up. CONCLUSIONS: The myCompass program is an effective public health program, facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12610000625077. PMID- 24237619 TI - Pulsed dye laser for the treatment of acquired progressive lymphangioma. PMID- 24237620 TI - Adapting lung cancer symptom investigation and referral guidelines for general practitioners in Australia: reflections on the utility of the ADAPTE framework. AB - RATIONALE: The ADAPTE framework was established to enhance efficiency in guideline development and to facilitate adaptation of high-quality clinical practice guidelines for a local context. It offers guideline developers a systematic methodology for guideline adaptation; however, the feasibility and usability of the process has not been widely evaluated. AIM: A pragmatic approach was undertaken throughout the evaluation of the ADATPE process throughout the development of a guide for general practitioners in Australia regarding the initial investigation of symptoms of lung cancer. At each step of the framework all members of the project team leading the development process reflected on the steps outlined in the ADAPTE. The reflections were collated into a lesson-learned log and analysed following completion of the project. RESULTS: Several opportunities for improvement were identified to improve usability and practicability of the ADAPTE framework. These items were both specific, in response to using steps and tools, and general issues concerned with the overall ADAPTE framework. Key challenges to using ADAPTE, highlighted in this study, were the lack of clarity about efficiency of the guideline adaptation process, level of assumed knowledge and expertise, and requirement of resources. In response to these challenges, modifications to the ADAPTE have been recommended. CONCLUSION: The ADAPTE framework offers an attractive alternative to de novo guideline synthesis in circumstances where high-quality, compatible guidelines already exist. Pending further evaluation, the modifications identified in this study may be applied to future versions of ADAPTE to improve usability and feasibility of the framework. PMID- 24237621 TI - Geographic information systems and logistic regression for high-resolution malaria risk mapping in a rural settlement of the southern Brazilian Amazon. AB - BACKGROUND: In Brazil, 99% of the cases of malaria are concentrated in the Amazon region, with high level of transmission. The objectives of the study were to use geographic information systems (GIS) analysis and logistic regression as a tool to identify and analyse the relative likelihood and its socio-environmental determinants of malaria infection in the Vale do Amanhecer rural settlement, Brazil. METHODS: A GIS database of georeferenced malaria cases, recorded in 2005, and multiple explanatory data layers was built, based on a multispectral Landsat 5 TM image, digital map of the settlement blocks and a SRTM digital elevation model. Satellite imagery was used to map the spatial patterns of land use and cover (LUC) and to derive spectral indices of vegetation density (NDVI) and soil/vegetation humidity (VSHI). An Euclidian distance operator was applied to measure proximity of domiciles to potential mosquito breeding habitats and gold mining areas. The malaria risk model was generated by multiple logistic regression, in which environmental factors were considered as independent variables and the number of cases, binarized by a threshold value was the dependent variable. RESULTS: Out of a total of 336 cases of malaria, 133 positive slides were from inhabitants at Road 08, which corresponds to 37.60% of the notifications. The southern region of the settlement presented 276 cases and a greater number of domiciles in which more than ten cases/home were notified. From these, 102 (30.36%) cases were caused by Plasmodium falciparum and 174 (51.79%) cases by Plasmodium vivax. Malaria risk is the highest in the south of the settlement, associated with proximity to gold mining sites, intense land use, high levels of soil/vegetation humidity and low vegetation density. CONCLUSIONS: Mid-resolution, remote sensing data and GIS-derived distance measures can be successfully combined with digital maps of the housing location of (non-) infected inhabitants to predict relative likelihood of disease infection through the analysis by logistic regression. Obtained findings on the relation between malaria cases and environmental factors should be applied in the future for land use planning in rural settlements in the Southern Amazon to minimize risks of disease transmission. PMID- 24237622 TI - Changes in mental state associated with prison environments: a systematic review. AB - OBJECTIVE: To develop an understanding of the stability of mental health during imprisonment through review of existing research evidence relating physical prison environment to mental state changes in prisoners. METHOD: A systematic literature search was conducted looking at changes in mental state and how this related to various aspects of imprisonment and the prison environment. RESULTS: Fifteen longitudinal studies were found, and from these, three broad themes were delineated: being imprisoned and aspects of the prison regime; stage of imprisonment and duration of sentence; and social density. Reception into prison results in higher levels of psychiatric symptoms that seem to improve over time; otherwise, duration of imprisonment appears to have no significant impact on mental health. Regardless of social density, larger prisons are associated with poorer mental state, as are extremes of social density. CONCLUSION: There are large gaps in the literature relating prison environments to changes in mental state; in particular, high-quality longitudinal studies are needed. Existing research suggests that although entry to prison may be associated with deterioration in mental state, it tends to improve with time. Furthermore, overcrowding, ever more likely as prison populations rise, is likely to place a particular burden on mental health services. PMID- 24237623 TI - Direct identification of pathogens from positive blood cultures using matrix assisted laser desorption-ionization time-of-flight mass spectrometry. AB - In recent years, matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has proved a rapid and reliable method for the identification of bacteria and yeasts that have already been isolated. The objective of this study was to evaluate this technology as a routine method for the identification of microorganisms directly from blood culture bottles (BCBs), before isolation, in a large collection of samples. For this purpose, 1000 positive BCBs containing 1085 microorganisms have been analysed by conventional phenotypic methods and by MALDI-TOF MS. Discrepancies have been resolved using molecular methods: the amplification and sequencing of the 16S rRNA gene or the Superoxide Dismutase gene (sodA) for streptococcal isolates. MALDI-TOF predicted a species- or genus-level identification of 81.4% of the analysed microorganisms. The analysis by episode yielded a complete identification of 814 out of 1000 analysed episodes (81.4%). MALDI-TOF identification is available for clinicians within hours of a working shift, as oppose to 18 h later when conventional identification methods are performed. Moreover, although further improvement of sample preparation for polymicrobial BCBs is required, the identification of more than one pathogen in the same BCB provides a valuable indication of unexpected pathogens when their presence may remain undetected in Gram staining. Implementation of MALDI-TOF identification directly from the BCB provides a rapid and reliable identification of the causal pathogen within hours. PMID- 24237625 TI - Epidemic gasoline exposures following Hurricane Sandy. AB - INTRODUCTION: Major adverse climatic events (MACEs) in heavily-populated areas can inflict severe damage to infrastructure, disrupting essential municipal and commercial services. Compromised health care delivery systems and limited utilities such as electricity, heating, potable water, sanitation, and housing, place populations in disaster areas at risk of toxic exposures. Hurricane Sandy made landfall on October 29, 2012 and caused severe infrastructure damage in heavily-populated areas. The prolonged electrical outage and damage to oil refineries caused a gasoline shortage and rationing unseen in the USA since the 1970s. This study explored gasoline exposures and clinical outcomes in the aftermath of Hurricane Sandy. METHODS: Prospectively collected, regional poison control center (PCC) data regarding gasoline exposure cases from October 29, 2012 (hurricane landfall) through November 28, 2012 were reviewed and compared to the previous four years. The trends of gasoline exposures, exposure type, severity of clinical outcome, and hospital referral rates were assessed. RESULTS: Two-hundred and eighty-three gasoline exposures were identified, representing an 18 to 283 fold increase over the previous four years. The leading exposure route was siphoning (53.4%). Men comprised 83.0% of exposures; 91.9% were older than 20 years of age. Of 273 home-based calls, 88.7% were managed on site. Asymptomatic exposures occurred in 61.5% of the cases. However, minor and moderate toxic effects occurred in 12.4% and 3.5% of cases, respectively. Gastrointestinal (24.4%) and pulmonary (8.4%) symptoms predominated. No major outcomes or deaths were reported. CONCLUSIONS: Hurricane Sandy significantly increased gasoline exposures. While the majority of exposures were managed at home with minimum clinical toxicity, some patients experienced more severe symptoms. Disaster plans should incorporate public health messaging and regional PCCs for public health promotion and toxicological surveillance. PMID- 24237624 TI - Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients. AB - BACKGROUND: The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self regulation and resistance to interference, inhibitory control, and environmental autonomy. METHODS: We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. RESULTS: Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). CONCLUSIONS: These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG. PMID- 24237626 TI - Amino acid substitutions in gyrA and parC associated with quinolone resistance in nalidixic acid-resistant Salmonella isolates. AB - This study was undertaken to identify and characterize amino acid substitutions in gyrA and parC related with quinolone resistance of 27 nalidixic acid-resistant (NaR) Salmonella isolates collected in poultry slaughterhouses in Korea. A total of 51 Salmonella isolates were detected from 44.8% (47/105) of the total samples from 15 poultry slaughterhouses examined, among which 27 (52.9%) NaR isolates were detected while ciprofloxacin (Cip) resistance was not present in the isolates. These 27 NaR isolates of DNA sequencing revealed that it contained three types of gyrA mutations in only D87 codon. Mutations in the D87 codon resulted in substitutions to G in most of the isolates, but D87Y and D87N exchanges were also detected. Although Cip resistance was absent, reduced susceptibility characterized by mutations in gyrA was apparent among Salmonella isolates from poultry slaughterhouses in Korea. PMID- 24237627 TI - Characterization of a novel DUF1618 gene family in rice. AB - Domain of unknown function (DUF) proteins represent a number of gene families that encode functionally uncharacterized proteins in eukaryotes. For example, DUF1618 family members in plants possess a 56-199-amino acid conserved domain and this family has not been described previously. Here, we report the characterization of 121 DUF1618 genes identified in the rice genome. Based on phylogenetic analysis, the rice DUF1618 family was divided into two major groups, each group consisting of two clades. Most DUF1618 genes with close phylogenetic relationships are located in gene clusters on the chromosomes, indicating that gene duplications increased the number of DUF1618 genes. A search for DUF1618 genes in genomic and/or expressed sequence tag databases for 35 other plant species showed that DUF1618 genes are only present in several monocot plants, suggesting that DUF1618 is a new gene family that originated after the dicot monocot divergence. Based on public microarray databases, most rice DUF1618 genes are expressed at relatively low levels. Further experimental analysis showed that the transcriptional levels of some DUF1618 genes varied in different cultivars, and some responded to stress and hormone conditions, suggesting their important roles for development and fitness in rice (Oryza sativa L.). PMID- 24237629 TI - Information literacy: perceptions of Brazilian HIV/AIDS researchers. AB - BACKGROUND: Information literacy has evolved with changes in lifelong learning. Can Brazilian health researchers search for and use updated scientific information? OBJECTIVES: To describe researchers' information literacy based on their perceptions of their abilities to search for and use scientific information and on their interactions with libraries. METHODS: Semi-structured interviews and focus group conducted with six Brazilian HIV/AIDS researchers. Analyses comprised the assessment of researchers as disseminators, their interactions with librarians, their use of information and communication technology and language. RESULTS: Interviewees believed they were partially qualified to use databases. They used words and phrases that indicated their knowledge of technology and terminology. They acted as disseminators for students during information searches. Researchers' abilities to interact with librarians are key skills, especially in a renewed context where libraries have, to a large extent, changed from physical spaces to digital environments. DISCUSSION: Great amounts of information have been made available, and researchers' participation in courses does not automatically translate into adequate information literacy. Librarians must help research groups, and as such, librarians' information literacy-related responsibilities in Brazil should be redefined and expanded. CONCLUSIONS: Students must develop the ability to learn quickly, and librarians should help them in their efforts. Librarians and researchers can act as gatekeepers for research groups and as information coaches to improve others' search abilities. PMID- 24237628 TI - Simultaneous subchronic exposure to selenium and diazinon as possible risk factor for osteoporosis in adult male rats. AB - BACKGROUND: Osteoporosis and its main health outcome, fragility fractures, are large and escalating health problems. Skeletal damage may be the critical result of low-level prolonged exposure to several xenobiotics in the general population, but the mechanisms of their adverse effects are not clearly understood. The current study was aimed to investigate the possible ability of simultaneous subchronic peroral administration of selenium (Se) and diazinon (DZN) to induce changes in bone of adult male rats.In our study, twenty 1-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males were exposed to 5 mg Na2SeO3/L and 40 mg of DZN/L in drinking water, for 90 days. Ten 1-month-old males without Se and DZN intoxication served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy. RESULTS: The body weight, femoral length and cortical bone thickness were significantly decreased in rats simultaneously exposed to Se and DZN (P < 0.05). These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta. The canals occurred only near endosteal surfaces in rats from the control group. Additionally, a smaller number of primary and secondary osteons, as well as a few resorption lacunae were observed near endosteal surfaces in rats simultaneously administered to Se and DZN. The resorption lacunae as typical structures of bone resorption manifestation are connected with an early stage of osteoporosis. Histomorphometric analysis revealed that area, perimeter, maximum and minimum diameters of primary osteons' vascular canals were significantly increased (P < 0.05) in the Se-DZN-exposed rats. On the other hand, all measured variables of Haversian canals and secondary osteons were considerable reduced (P < 0.05) in these rats. CONCLUSIONS: Simultaneous subchronic peroral exposure to Se and DZN induces changes in macroscopic and microscopic structures of the femurs in adult male rats, and also it can be considered as possible risk factor for osteoporosis. The current study contributes to the knowledge on damaging impact of several xenobiotics on the bone. PMID- 24237630 TI - Hibernoma mimicking metastasis on positron emission tomography-computed tomography imaging: a misleading finding in oncologic patient follow-up. PMID- 24237631 TI - Medical marijuana for epilepsy: winds of change. PMID- 24237632 TI - Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. AB - Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures. PMID- 24237633 TI - Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. AB - BACKGROUND: We previously developed an immunotherapy treatment utilizing a cancer vaccine reagent KIF20A-66 in order to treat pancreatic cancer. KIF20A-66 is HLA A24-restricted epitope peptide derived from KIF20A, a member of kinesin super family protein 20A that is significantly transactivated in pancreatic cancer. In this report, we further demonstrated non-randomized, open-label, single centered phase I/II clinical trial of immunotherapy using the KIF20A-66 peptide for the patients with advanced pancreatic cancer. METHODS: Vaccination was performed to the patients with metastatic pancreatic cancer, in whom gemcitabine-based therapy had failed. In phase I study, KIF20A-66 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 1.0 and 3.0 mg/body, 6 patients/1 cohort). After safety was assessed, phase II study was conducted using 3.0 mg of KIF20A-66 peptide. RESULTS: KIF20A-66 peptide vaccination was well tolerated in the doses we examined and tumor responses after 1 month of the treatment were evaluated. Among 29 patients who completed one course of the treatment at least, stable disease (SD) was found in 21 cases, while progressive disease (PD) was found in 8 cases, indicating that the disease control rate was 72%. Objective tumor shrinkage was observed in 8 cases, including 1 case of complete response (CR). The median survival time (MST) and progression free survival time (PFS) were 142 days and 56 days, respectively. These results clearly demonstrate that overall survival of the patients was significantly prolonged, compared to the historical controls of 9 cases with unmatched HLA in the same hospital (MST: 83 days), as well as 81 cases in our and other hospitals (MST: 63 days). CONCLUSION: The patients vaccinated with KIF20A-66 peptide had better prognosis than the control group with best supportive care (BSC). Thus, we concluded that KIF20A-66 vaccination is significantly effective as an immunotherapy against advanced pancreatic cancer. KIF20A-66 peptide was well tolerable in the dose of either 1.0 mg or 3.0 mg/body, and effectively induced peptide-specific response of cytotoxic T lymphocyte (CTL). Further clinical study using this peptide is a promising approach for advanced pancreatic cancer to achieve high potential benefit for better prognosis. CLINICAL TRIAL REGISTRATION: UMIN-CTR, number UMIN000004919. PMID- 24237634 TI - Influence of neighbourhood purchasing power on breastfeeding at four months of age: a Swedish population-based cohort study. AB - BACKGROUND: Parental socioeconomic status (SES) is an important determinant in child health, influencing beneficial factors such as breastfeeding. A better understanding of the influence of neighbourhood-level SES measures, relating to spatial determinants, might lead to targeted actions to promote breastfeeding during infancy. METHODS: A cross-sectional study analysis the association between breastfeeding at four months of age and neighbourhood purchasing power, taking account of individual-level variables including maternal age, smoking and parental level of education. Data were obtained from a prospective population- based cohort study recruited from birth in 2007-2008 in the Halland region, southwestern Sweden. Questionnaire data on the individual-level variables and the outcome variable of breastfeeding at four months (yes/no) were used (n=2,407). Each mother was geo-coded with respect to her residential parish (there are 61 parishes in the region) and then stratified by parish-level household purchasing power. It emerged that four neighbourhood characteristics were reasonable to use, viz. <10%, 10-19%, 20-29% and >= 30% of the resident families with low purchasing power. RESULTS: The proportion of mothers not breastfeeding at four months of age showed a highly significant trend across the neighbourhood strata (p=0.00004): from 16.3% (< 10% with low purchasing power) to 29.4% (>= 30% with low purchasing power), yielding an OR of 2.24 (95% confidence interval: 1.45-3.16). After adjusting for the individual-level variables, the corresponding OR=1.63 (1.07 2.56) was significant and the trend across the strata was still evident (p=0.05). A multi-level analysis estimated that, in the neighbourhoods with >= 30% of the families with low purchasing power, 20% more mothers than expected, taking account of the individual-level factors, reported no breastfeeding at four months of age (>= 95% posterior probability of an elevated observed-to-expected ratio). CONCLUSION: The neighbourhood purchasing power provided a spatial determinant of low numbers of mothers breastfeeding at four months of age, which could be relevant to consider for targeted actions. The elevated observed-to-expected ratio in the neighbourhoods with the lowest purchasing power points toward a possible contextual influence. PMID- 24237635 TI - Are the specialized bird ticks, Ixodes arboricola and I. frontalis, competent vectors for Borrelia burgdorferi sensu lato? AB - Our study tested whether two European bird-specialized ticks, Ixodes arboricola and I. frontalis, can act as vectors in the transmission cycles of Borrelia burgdorferi s.l. The ticks have contrasting ecologies but share songbird hosts (such as the great tit, Parus major) with the generalist I. ricinus which may therefore act as a bridging vector. In the first phase of the experiment, we obtained Borrelia-infected ornithophilic nymphs by exposing larvae to great tits that had previously been exposed to I. ricinus nymphs carrying a community of genospecies (Borrelia garinii, valaisiana, afzelii, burgdorferi s.s., spielmanii). Skin samples showed that birds selectively amplified B. garinii and B. valaisiana. The spirochetes were transmitted to the ornithophilic ticks and survived moulting, leading to infection rates of 16% and 27% in nymphs of I. arboricola and I. frontalis respectively. In the second phase, pathogen-free great tits were exposed to the Borrelia-infected ornithophilic nymphs. None of these ticks were able to infect the birds, as indicated by the tissue samples. Analysis of xenodiagnostic I. ricinus larvae found no evidence for co-feeding or systemic transmission of B. burgdorferi s.l. These outcomes do not support the occurrence of enzootic cycles of Borrelia burgdorferi s.l. involving songbirds and their specialized ornithophilic ticks. PMID- 24237636 TI - Genomic architecture of ecologically divergent body shape in a pair of sympatric crater lake cichlid fishes. AB - Determining the genetic bases of adaptations and their roles in speciation is a prominent issue in evolutionary biology. Cichlid fish species flocks are a prime example of recent rapid radiations, often associated with adaptive phenotypic divergence from a common ancestor within a short period of time. In several radiations of freshwater fishes, divergence in ecomorphological traits - including body shape, colour, lips and jaws - is thought to underlie their ecological differentiation, specialization and, ultimately, speciation. The Midas cichlid species complex (Amphilophus spp.) of Nicaragua provides one of the few known examples of sympatric speciation where species have rapidly evolved different but parallel morphologies in young crater lakes. This study identified significant QTL for body shape using SNPs generated via ddRAD sequencing and geometric morphometric analyses of a cross between two ecologically and morphologically divergent, sympatric cichlid species endemic to crater Lake Apoyo: an elongated limnetic species (Amphilophus zaliosus) and a high-bodied benthic species (Amphilophus astorquii). A total of 453 genome-wide informative SNPs were identified in 240 F2 hybrids. These markers were used to construct a genetic map in which 25 linkage groups were resolved. Seventy-two segregating SNPs were linked to 11 QTL. By annotating the two most highly supported QTL linked genomic regions, genes that might contribute to divergence in body shape along the benthic-limnetic axis in Midas cichlid sympatric adaptive radiations were identified. These results suggest that few genomic regions of large effect contribute to early stage divergence in Midas cichlids. PMID- 24237638 TI - The limitations of pulsed-field gel electrophoresis for analysis of Yersinia enterocolitica isolates. AB - This study describes the analysis of 432 isolates of Yersinia enterocolitica by pulsed-field gel electrophoresis (PFGE). PFGE had a high level of discrimination with biotype 1A isolates (Simpson's Diversity Index 0.997), but with the clinically important biotypes 2, 3 and 4, the discriminatory ability of PFGE was so low as to severely limit its usefulness (DI <0.6). For biotypes 2, 3 and 4, 79% or more of isolates of each biotype were of just three different PFGE profiles. Because of this, four known outbreaks of yersiniosis would not have been identified by PFGE analysis. However, a previously unrecognized potential outbreak of yersiniosis caused by biotype 4 isolates was identified on the basis of a rare PFGE genotype with spatial and temporal clustering. We conclude that PFGE has a very limited application to the genotyping of Y. enterocolitica biotypes 2, 3 and 4, and inferences based on finding indistinguishable PFGE profiles among cases or between cases and sources need to be substantiated using alternative typing tools, or strong epidemiological evidence. PMID- 24237639 TI - Educational programming in undergraduate and graduate academic curricula: friend or foe to accelerating evidence-based practice? PMID- 24237637 TI - Functional characterization of an ornithine cyclodeaminase-like protein of Arabidopsis thaliana. AB - BACKGROUND: In plants, proline synthesis occurs by two enzymatic steps starting from glutamate as a precursor. Some bacteria, including bacteria such as Agrobacterium rhizogenes have an Ornithine Cyclodeaminase (OCD) which can synthesize proline in a single step by deamination of ornithine. In A. rhizogenes, OCD is one of the genes transferred to the plant genome during the transformation process and plants expressing A. rhizogenes OCD have developmental phenotypes. One nuclear encoded gene of Arabidopsis thaliana has recently been annotated as an OCD (OCD-like; referred to here as AtOCD) but nothing is known of its function. As proline metabolism contributes to tolerance of low water potential during drought, it is of interest to determine if AtOCD affects proline accumulation or low water potential tolerance. RESULTS: Expression of AtOCD was induced by low water potential stress and by exogenous proline, but not by the putative substrate ornithine. The AtOCD protein was plastid localized. T-DNA mutants of atocd and AtOCD RNAi plants had approximately 15% higher proline accumulation at low water potential while p5cs1-4/atocd double mutants had 40% higher proline than p5cs1 at low water potential but no change in proline metabolism gene expression which could directly explain the higher proline level. AtOCD overexpression did not affect proline accumulation. Enzymatic assays with bacterially expressed AtOCD or AtOCD purified from AtOCD:Flag transgenic plants did not detect any activity using ornithine, proline or several other amino acids as substrates. Moreover, AtOCD mutant or over-expression lines had normal morphology and no difference in root elongation or flowering time, in contrast to previous report of transgenic plants expressing A. rhizogenes OCD. Metabolite analysis found few differences between AtOCD mutants and overexpression lines. CONCLUSIONS: The Arabidopsis OCD-like protein (AtOCD) may not catalyze ornithine to proline conversion and this is consistent with observation that three residues critical for activity of bacterial OCDs are not conserved in AtOCD. AtOCD was, however, stress and proline induced and lack of AtOCD expression increased proline accumulation by an unknown mechanism which did not require expression of P5CS1, the main enzyme responsible for stress-induced proline synthesis from glutamate. The results suggest that AtOCD may have function distinct from bacterial OCDs. PMID- 24237640 TI - Surgical treatment of ingrown toe nail: the Monaldi technique, a new simple proposal. PMID- 24237641 TI - A review of FDA-approved treatment options in bipolar depression. AB - OBJECTIVES/INTRODUCTION: Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression. METHODS: A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality. RESULTS: Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational. CONCLUSION: Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression. PMID- 24237642 TI - Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. AB - OBJECTIVE: To investigate the association between neuroleptic malignant syndrome (NMS) and levels of antipsychotic exposure. METHOD: Electronic health record data systematically screened from a large mental health service provider in southeast London provided 67 NMS cases which were individually matched with 254 controls on age, gender, and primary psychiatric diagnosis. Data on psychotropic agents, combinations, dose, and dose change of antipsychotic prescriptions over the preceding 5 (oral agents) or 15 days (depot agents) were extracted and compared between groups using conditional logistic regression models. RESULTS: NMS was associated with higher number of antipsychotic agents used, use of first generation agents or aripiprazole, use of first-generation agents only or cross generation agents, and higher mean and maximum daily doses. In further analyses, associations with antipsychotics type remained significant when adjusted for dose, but those with dose were attenuated following adjustment for type. The specific use of haloperidol, aripiprazole, depot flupentixol, and benzodiazepines was independently associated with NMS. Non-white ethnicity was also found to be associated with NMS. CONCLUSION: NMS was primarily associated with type of antipsychotic and polypharmacy rather than overall dose. Variation in risk by ethnicity requires further research. PMID- 24237644 TI - Transition of care in inflammatory bowel disease: mind the gap! Theory, practice and recommendations for an Australian context. PMID- 24237643 TI - Induction of pro-inflammatory response of the placental trophoblast by Plasmodium falciparum infected erythrocytes and TNF. AB - BACKGROUND: Plasmodium falciparum placental malaria is characterized by the sequestration of infected erythrocytes (IEs) in the placental intervillous space via adherence to chondroitin sulphate A (CSA), production of inflammatory molecules, and leukocytes infiltration. Previous reports suggest that the syncytiotrophoblast (ST) immunologically responds to IEs contact. This study explores the inflammatory response induced in BeWo cells by adherence of IEs and TNFstimulation. METHODS: A non-syncitialized BeWo cells (trophoblast model) were used to evaluate its response to CSA-adherents IEs (FCB1csa, FCB2csa, FCR3csa, 3D7csa) and TNF stimulation. Expression of membrane ICAM-1 (mICAM-1) receptor in BeWo cells was quantified by flow cytometry and the IL-8, IL-6 and soluble ICAM-1 (sICAM-1) concentrations were quantified by enzyme-linked immunosorbentassay (ELISA) in BeWo stimulated supernatants. RESULTS: BeWo cells stimulated with TNF and CSA-adherents IEs of FCB1csa and 3D7csa (strains with higher adhesion) increase the expression of ICAM-1 on the surface of cells and the secretion of immune factors IL-8, IL-6 and sICAM-1. This inflammatory response appears to be related to the level of adherence of IEs because less adherent strains do not induce significant changes. CONCLUSIONS: It was found that BeWo cells responds to CSA-IEs and to TNF favouring a placental pro-inflammatory environment, evidenced by increases in the expression of membrane mICAM-1 and release of soluble ICAM-1, as well as the IL-8 and IL-6 secretion. The expression of ICAM-1 in BeWo cells might be associated to an increase in leukocyte adhesion to the trophoblast barrier, promoting greater inflammation, while the sICAM-1 release could be a protection mechanism activated by trophoblastic cells, in order to regulate the local inflammatory response. PMID- 24237645 TI - Multifocal motor neuropathy and muscle hypertrophy. AB - Multifocal motor neuropathy is frequently an asymmetrical neuropathy predominantly affecting the upper limbs. Patients present with weakness, fasciculations and distal muscle wasting. Hypertrophy of muscles is very infrequently reported. We present two cases of multifocal motor neuropathy with upper limb muscle hypertrophy and discuss possible pathophysiological mechanisms. Botulinum toxin may be useful to alleviate cramp. PMID- 24237646 TI - Gemcitabine-induced thrombotic microangiopathy. AB - Thrombotic microangiopathy (TMA) is a microvascular occlusive disorder characterised by platelet aggregation, thrombocytopenia and end-organ damage. It is commonly idiopathic, although several drug classes, including cytotoxic chemotherapy, have been implicated. Several of cases of gemcitabine-induced TMA have been documented with incidence likely to increase with the escalating use of gemcitabine. We report the cases of two patients who developed TMA while on gemcitabine chemotherapy. PMID- 24237647 TI - Denosumab-induced hypocalcaemia in high bone turnover states of malignancy and secondary hyperparathyroidism from renal failure. AB - Denosumab, an anti-resorptive treatment for osteoporosis and skeletal metastases from solid tumours, can cause hypocalcaemia. The incidence may be higher than previously reported due to varying serum calcium cut-off and timing of measurement. The following cases illustrate patients at risk of hypocalcaemia despite supplementation. These populations, with underlying high bone turnover from metastatic bone disease or secondary hyperparathyroidism due to renal failure, may require closer monitoring of calcium levels post-denosumab administration. PMID- 24237648 TI - Impact of the 2009 Melbourne heatwave on a major public hospital. AB - In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems. PMID- 24237649 TI - Teaching Junior Medical Officers safe and effective prescribing. AB - Medication errors are an iatrogenic threat to patient safety, and recently graduated Junior Medical Officers (JMOs) are a common source of these errors. A ward-based, physician-led, small-group interactive teaching session was developed to improve JMOs competence in prescribing. The ability of JMOs to detect problems in mock medication charts before and after the teaching session was assessed, with the majority improving after the intervention, a result sustained on re testing later in the year. The teaching sessions were well received by JMOs. PMID- 24237650 TI - Demonstrable professionalism: linking patient-centred care and revalidation. AB - The move by the Medical Board of Australia to commence a conversation with the medical profession about revalidation reflects that patient-centred care is at the heart of good medical practice. Patients judge their doctors' commitment to them based on whether their individual interactions with doctors meet their needs. We argue that ensuring that doctors are continuing to perform at a level that the community regards as acceptable is a demonstration of an individual doctor's professionalism and thus their commitment to patient-centred care. This impacts on the profession as a whole, which needs to commit to what we call 'demonstrable professionalism'--the ongoing and active demonstration of performance that the community regards as acceptable. This needs to be supported by organisations in which doctors work, reflecting the importance of organisational context to clinical practice. Revalidation processes thus need both to reflect the work of doctors and be meaningful to the community. The move to consider revalidation of doctors by regulatory authorities should not be seen by the profession as a threat, but more as an opportunity to demonstrate the profession's commitment to patient-centred care. PMID- 24237651 TI - Antibodies to Australian bat lyssavirus in an asymptomatic bat carer. PMID- 24237652 TI - Cost of misdiagnosing difficult asthma. PMID- 24237653 TI - Management dilemmas in a case of angioedema with normal C1 inhibitor function during pregnancy. PMID- 24237654 TI - Improving the logic and rigour of delirium trials. PMID- 24237656 TI - Combined analysis of the non-pneumatic anti-shock garment on mortality from hypovolemic shock secondary to obstetric hemorrhage. AB - BACKGROUND: Obstetric hemorrhage is the leading cause of maternal mortality, particularly in low-resource settings where women face significant delays in accessing definitive treatment. The Non-pneumatic Anti-Shock Garment (NASG) is a first-aid device to stabilize women in hypovolemic shock secondary to obstetric hemorrhage. Prior studies on the effectiveness of the NASG have suffered from small sample sizes and insufficient statistical power. We sought to generate a summary effect estimate of this intervention by combining data from all previous quasi-experimental studies. METHODS: Five quasi-experimental studies that tested the NASG as treatment for hypovolemic shock secondary to obstetric hemorrhage at the tertiary care facility level were included in the analysis. We evaluated heterogeneity of effect across studies and calculated pooled odds ratios. We also conducted a subgroup analysis among women in the most severe condition. RESULTS: Participant characteristics were similar across studies with some variation in hemorrhage etiology. Median blood loss was at least 50% lower in the intervention group than the control group. The pooled odds ratio suggested that NASG intervention was associated with a 38% significantly reduced odds of mortality among the overall sample, and a 59% significantly reduced odds of mortality among the most severe women. CONCLUSIONS: The results from this combined analysis suggest that NASG intervention is associated with a reduced odds of death for women with hypovolemic shock secondary to obstetric hemorrhage. Further research should focus on application of the NASG at the community or primary health care level, and utilize a more robust methodology. PMID- 24237655 TI - Impact of a 4q25 genetic variant in atrial flutter and on the risk of atrial fibrillation after cavotricuspid isthmus ablation. AB - BACKGROUND: The prediction of atrial fibrillation (AF) following catheter ablation of atrial flutter (Afl) would be helpful to facilitate targeted arrhythmia monitoring and anti-coagulation strategies. A single nucleotide polymorphism, rs2200733, is strongly associated with AF. We sought to characterize the association between rs2200733 and prevalent Afl and to determine if the variant could predict AF after cavotricuspid isthmus ablation. METHODS AND RESULTS: We performed a genetic association study of 295 patients with Afl and/or AF and 469 controls using multivariable logistic regression. The variant was then assessed as a predictor of incident AF after cavotricuspid isthmus ablation in 87 consecutive typical Afl patients with Cox proportional hazards models. The rs2200733 rare allele was associated with an adjusted 2.06-fold increased odds of isolated Afl (95% CI: 1.13-3.76, P = 0.019) and an adjusted 2.79-fold increased odds of a combined phenotype of AF and Afl (95% CI: 1.81-4.28, P < 0.001). Following catheter ablation for Afl, carrier status of rs2200733 failed to predict an increased risk of AF either among all subjects (adjusted HR: 0.94; 95% CI: 0.58-1.53, P = 0.806) or among those with isolated Afl (adjusted HR: 1.29; 95% CI: 0.51-3.26, P = 0.585). CONCLUSIONS: Our study demonstrates that Afl, whether occurring in isolation or along with AF, is associated with the rs2200733 AF risk allele. Genetic carrier status of rs2200733 failed to predict an increased risk of incident or recurrent AF following catheter ablation for Afl. These findings suggest that the causal mechanism associated with rs2200733 is germane to both AF and Afl. PMID- 24237657 TI - Cervical cancer screening: a prospective cohort study of the effects of historical patient compliance and a population-based informatics prompted reminder on screening rates. AB - AIMS AND OBJECTIVES: The aim of this study was to assess the impact of historical screening compliance with the effectiveness of patient reminder letters on cervical cancer screening rates. METHOD: Using population-based informatics systems, women with no cervical cancer screening in the prior 3 years were identified in two primary care clinics, Mayo Family Clinic Northeast (NE; n = 1613) and Northwest (NW; n = 1088). Patients were divided into two compliance groups: overdue/unknown screening status at study start or previously compliant. The NE Clinic sent reminder letters over a 6 months window to patients eligible for screening at the study start or during the study that were also identified as employees/dependents (E/D). There were 795 intervention (NE Clinic E/D patients) and 1906 control subjects. Using an intent-to-treat analysis, differences in screening rates were assessed. RESULTS: A higher unadjusted screening rate was observed for the E/D group than the non-E/D group at both sites (32.7 versus 18.2% at NW, P < 0.001; 39.0 versus 14.7% at NE, P < 0.001). For the historically compliant group, unadjusted screening rates were higher for those who received letters (E/D subjects at NE) versus those who did not (E/D subjects at NW; 56.1 versus 44.5%, P = 0.01). No difference was observed between E/D subjects at NE (received letters) and NW (no letters) for the overdue/unknown group (27.4 versus 25.9%, P = 0.62). There was no difference in screening rates for non-E/D subjects at NE versus at NW (none of whom received letters) for both the compliant (24.2 versus 30.6%, P = 0.18) and the overdue/unknown groups (11.9 versus 13.0%, P = 0.59). Multivariate logistic regression models showed a significant overall effect of E/D status (P = 0.006), compliance group (P < 0.001), and the interaction between clinic site and E/D status (P = 0.04). CONCLUSION: Among insured women, reminder letters appear to improve cervical cancer screening rates for those with a history of screening compliance. Reminder letters appear insufficient to motivate women if screening is overdue. Further investigation of the cohort of women overdue for screening is needed to develop interventions to successfully target this group. PMID- 24237658 TI - An exact approach for studying cargo transport by an ensemble of molecular motors. AB - BACKGROUND: Intracellular transport is crucial for many cellular processes where a large fraction of the cargo is transferred by motor-proteins over a network of microtubules. Malfunctions in the transport mechanism underlie a number of medical maladies.Existing methods for studying how motor-proteins coordinate the transfer of a shared cargo over a microtubule are either analytical or are based on Monte-Carlo simulations. Approaches that yield analytical results, while providing unique insights into transport mechanism, make simplifying assumptions, where a detailed characterization of important transport modalities is difficult to reach. On the other hand, Monte-Carlo based simulations can incorporate detailed characteristics of the transport mechanism; however, the quality of the results depend on the number and quality of simulation runs used in arriving at results. Here, for example, it is difficult to simulate and study rare-events that can trigger abnormalities in transport. RESULTS: In this article, a semi analytical methodology that determines the probability distribution function of motor-protein behavior in an exact manner is developed. The method utilizes a finite-dimensional projection of the underlying infinite-dimensional Markov model, which retains the Markov property, and enables the detailed and exact determination of motor configurations, from which meaningful inferences on transport characteristics of the original model can be derived. CONCLUSIONS: Under this novel probabilistic approach new insights about the mechanisms of action of these proteins are found, suggesting hypothesis about their behavior and driving the design and realization of new experiments.The advantages provided in accuracy and efficiency make it possible to detect rare events in the motor protein dynamics, that could otherwise pass undetected using standard simulation methods. In this respect, the model has allowed to provide a possible explanation for possible mechanisms under which motor proteins could coordinate their motion. PMID- 24237660 TI - Postradiation cutaneous angiosarcoma of the breast: a diagnosis to keep in mind. PMID- 24237659 TI - Lessons from the modular organization of the transcriptional regulatory network of Bacillus subtilis. AB - BACKGROUND: The regulation of gene expression at the transcriptional level is a fundamental process in prokaryotes. Among the different kind of mechanisms modulating gene transcription, the one based on DNA binding transcription factors, is the most extensively studied and the results, for a great number of model organisms, have been compiled making it possible the in silico construction of their corresponding transcriptional regulatory networks and the analysis of the biological relationships of the components of these intricate networks, that allows to elucidate the significant aspects of their organization and evolution. RESULTS: We present a thorough review of each regulatory element that constitutes the transcriptional regulatory network of Bacillus subtilis. For facilitating the discussion, we organized the network in topological modules. Our study highlight the importance of sigma factors, some of them acting as master regulators which characterize modules by inter- or intra-connecting them and play a key role in the cascades that define relevant cellular processes in this organism. We discussed that some particular functions were distributed in more than one module and that some modules contained more than one related function. We confirm that the presence of paralogous proteins confers advantages to B. subtilis to adapt and select strategies to successfully face the extreme and changing environmental conditions in which it lives. CONCLUSIONS: The intricate organization is the product of a non-random network evolution that primarily follows a hierarchical organization based on the presence of transcription and sigma factor, which is reflected in the connections that exist within and between modules. PMID- 24237661 TI - Deep subsurface sulfate reduction and methanogenesis in the Iberian Pyrite Belt revealed through geochemistry and molecular biomarkers. AB - The Iberian Pyrite Belt (IPB, southwest of Spain), the largest known massive sulfide deposit, fuels a rich chemolithotrophic microbial community in the Rio Tinto area. However, the geomicrobiology of its deep subsurface is still unexplored. Herein, we report on the geochemistry and prokaryotic diversity in the subsurface (down to a depth of 166 m) of the Iberian Pyritic belt using an array of geochemical and complementary molecular ecology techniques. Using an antibody microarray, we detected polymeric biomarkers (lipoteichoic acids and peptidoglycan) from Gram-positive bacteria throughout the borehole. DNA microarray hybridization confirmed the presence of members of methane oxidizers, sulfate-reducers, metal and sulfur oxidizers, and methanogenic Euryarchaeota. DNA sequences from denitrifying and hydrogenotrophic bacteria were also identified. FISH hybridization revealed live bacterial clusters associated with microniches on mineral surfaces. These results, together with measures of the geochemical parameters in the borehole, allowed us to create a preliminary scheme of the biogeochemical processes that could be operating in the deep subsurface of the Iberian Pyrite Belt, including microbial metabolisms such as sulfate reduction, methanogenesis and anaerobic methane oxidation. PMID- 24237663 TI - Characterization of single 1.8-nm Au nanoparticle attachments on AFM tips for single sub-4-nm object pickup. AB - This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the tip of an atomic force microscopy (AFM) probe through the application of a current-limited bias voltage. The resulting probe is capable of picking up individual objects at the sub-4-nm scale. We also discuss the mechanisms involved in the attachment of the Au-NP to the very apex of an AFM probe tip. The Au-NP-modified AFM tips were used to pick up individual 4-nm quantum dots (QDs) using a chemically functionalized method. Single QD blinking was reduced considerably on the Au-NP-modified AFM tip. The resulting AFM tips present an excellent platform for the manipulation of single protein molecules in the study of single protein-protein interactions. PMID- 24237662 TI - A comparative study of clinical Aeromonas dhakensis and Aeromonas hydrophila isolates in southern Taiwan: A. dhakensis is more predominant and virulent. AB - Aeromonas dhakensis, often phenotypically identified as Aeromonas hydrophila, is an important human pathogen. The present study aimed to compare the clinical and biological features of A. dhakensis and A. hydrophila isolates from human wounds. A total of 80 Aeromonas wound isolates collected between January 2004 and April 2011 were analysed. The species was identified by the DNA sequence matching of rpoD and gyrB (or rpoB if necessary). Most of the Aeromonas isolates were identified as A. dhakensis (37, 46.3%), and 13 (16.3%) as A. hydrophila. Both species alone can cause severe skin and soft-tissue infections. More A. dhakensis isolates were found in wounds exposed to environmental water (32.4% vs 0%, p 0.042). More biofilm formation was noted among A. dhakensis isolates (mean optical density at 570 nm, 1.23 +/- 0.09 vs 0.78 +/- 0.21, p 0.03). The MICs of ceftriaxone, imipenem and gentamicin for A. dhakensis isolates were higher (p <0.0001, <0.04, and <0.01, respectively). The survival rates of Caenorhabditis elegans co-incubated with A. dhakensis from day 1 to day 3 were lower than those of worms infected with A. hydrophila in liquid toxicity assays (all p values <0.01). Isolates of A. dhakensis exhibited more cytotoxicity, as measured by the released leucocyte lactate dehydrogenase levels in human normal skin fibroblast cell lines (29.6 +/- 1.2% vs 20.6 +/- 0.6%, p <0.0001). The cytotoxin gene ast was primarily present in A. hydrophila isolates (100% vs 2.7%, p <0.0001). In summary, A. dhakensis is the predominant species among Aeromonas wound isolates, and more virulent than A. hydrophila. PMID- 24237664 TI - UBL1 of Fusarium verticillioides links the N-end rule pathway to extracellular sensing and plant pathogenesis. AB - Fusarium verticillioides produces fumonisin mycotoxins during colonization of maize. Currently, molecular mechanisms underlying responsiveness of F.verticillioides to extracellular cues during pathogenesis are poorly understood. In this study, insertional mutants were created and screened to identify genes involved in responses to extracellular starch. In one mutant, the restriction enzyme-mediated integration cassette disrupted a gene (UBL1) encoding a UBR-Box/RING domain E3 ubiquitin ligase involved in the N-end rule pathway. Disruption of UBL1 in F.verticillioides (Deltaubl1) influenced conidiation, hyphal morphology, pigmentation and amylolysis. Disruption of UBL1 also impaired kernel colonization, but the ratio of fumonisin B1 per unit growth was not significantly reduced. The inability of a Deltaubl1 mutant to recognize an N-end rule degron confirmed involvement of UBL1 in the N-end rule pathway. Additionally, Ubl1 physically interacted with two G protein alpha subunits of F.verticillioides, thus implicating UBL1 in G protein-mediated sensing of the external environment. Furthermore, deletion of the UBL1 orthologue in F.graminearum reduced virulence on wheat and maize, thus indicating that UBL1 has a broader role in virulence among Fusarium species. This study provides the first linkage between the N-end rule pathway and fungal pathogenesis, and illustrates a new mechanism through which fungi respond to the external environment. PMID- 24237665 TI - Genomic inference accurately predicts the timing and severity of a recent bottleneck in a nonmodel insect population. AB - The analysis of molecular data from natural populations has allowed researchers to answer diverse ecological questions that were previously intractable. In particular, ecologists are often interested in the demographic history of populations, information that is rarely available from historical records. Methods have been developed to infer demographic parameters from genomic data, but it is not well understood how inferred parameters compare to true population history or depend on aspects of experimental design. Here, we present and evaluate a method of SNP discovery using RNA sequencing and demographic inference using the program deltaadeltai, which uses a diffusion approximation to the allele frequency spectrum to fit demographic models. We test these methods in a population of the checkerspot butterfly Euphydryas gillettii. This population was intentionally introduced to Gothic, Colorado in 1977 and has as experienced extreme fluctuations including bottlenecks of fewer than 25 adults, as documented by nearly annual field surveys. Using RNA sequencing of eight individuals from Colorado and eight individuals from a native population in Wyoming, we generate the first genomic resources for this system. While demographic inference is commonly used to examine ancient demography, our study demonstrates that our inexpensive, all-in-one approach to marker discovery and genotyping provides sufficient data to accurately infer the timing of a recent bottleneck. This demographic scenario is relevant for many species of conservation concern, few of which have sequenced genomes. Our results are remarkably insensitive to sample size or number of genomic markers, which has important implications for applying this method to other nonmodel systems. PMID- 24237667 TI - Animal Disease Import Risk Analysis--a Review of Current Methods and Practice. AB - The application of risk analysis to the spread of disease with international trade in animals and their products, that is, import risk analysis (IRA), has been largely driven by the Sanitary and Phytosanitary (SPS) agreement of the World Trade Organization (WTO). The degree to which the IRA standard established by the World Organization for Animal Health (OIE), and associated guidance, meets the needs of the SPS agreement is discussed. The use of scenario trees is the core modelling approach used to represent the steps necessary for the hazard to occur. There is scope to elaborate scenario trees for commodity IRA so that the quantity of hazard at each step is assessed, which is crucial to the likelihood of establishment. The dependence between exposure and establishment suggests that they should fall within the same subcomponent. IRA undertaken for trade reasons must include an assessment of consequences to meet SPS criteria, but guidance is sparse. The integration of epidemiological and economic modelling may open a path for better methods. Matrices have been used in qualitative IRA to combine estimates of entry and exposure, and consequences with likelihood, but this approach has flaws and better methods are needed. OIE IRA standards and guidance indicate that the volume of trade should be taken into account, but offer no detail. Some published qualitative IRAs have assumed current levels and patterns of trade without specifying the volume of trade, which constrains the use of IRA to determine mitigation measures (to reduce risk to an acceptable level) and whether the principle of equivalence, fundamental to the SPS agreement, has been observed. It is questionable whether qualitative IRA can meet all the criteria set out in the SPS agreement. Nevertheless, scope exists to elaborate the current standards and guidance, so they better serve the principle of science-based decision-making. PMID- 24237666 TI - Evaluating area-level spatial clustering of Salmonella Enteritidis infections and their socioeconomic determinants in the greater Toronto area, Ontario, Canada (2007 - 2009): a retrospective population-based ecological study. AB - BACKGROUND: There have been only a few region-level ecological studies conducted in Canada investigating enteric infections in humans. Our study objectives were to 1) assess the spatial clustering of Salmonella enterica serotype Enteritidis (S. Enteritidis) human infections in the Greater Toronto Area, and 2) identify underlying area-level associations between S. Enteritidis infection rates and socioeconomic status (SES) indicators that might explain the clustering of infections. METHODS: Retrospective data on S. Enteritidis infections from 2007 to 2009 were obtained from Ontario's reportable disease surveillance database and were grouped at the forward sortation area (FSA) - level. A spatial scan statistic was employed to identify FSA-level spatial clusters of high infection rates. Negative binomial regression was used to identify FSA-level associations between S. Enteritidis infection rates and SES indicators obtained from the 2006 Census of Canada. Global Moran's I statistic was used to evaluate the final model for residual spatial clustering. RESULTS: A spatial cluster that included nine neighbouring FSAs was identified in downtown Toronto. A significant positive curvilinear relationship was observed between S. Enteritidis infection rates and FSA-level average number of children at home per census family. Areas with high and areas with low average median family income had higher infection rates than FSAs with medium average median family income. Areas with a high proportion of visible minority population had lower infection rates than FSAs with a medium proportion of visible minority population. The Moran's I statistic was not significant, indicating that no residual spatial autocorrelation was present after accounting for the SES variables in the final model. CONCLUSIONS: Our study demonstrated that FSAs with high and low average median family income, medium proportion of visible minority population, and high average number of children at home per census family had the highest S. Enteritidis infection rates. These areas should be targeted when designing disease control and prevention programs. Future studies are needed in areas with high S. Enteritidis infection rates to identify sources of environmental contamination of the local food supply, to assess food safety practices at local food markets, retail stores, and restaurants, and to identify novel individual-level risk factors. PMID- 24237668 TI - Detection of common mutations in sporadic primary localized cutaneous amyloidosis by DNA mass spectrometry. PMID- 24237669 TI - Brief assessment of supine heart rate variability in normal weight, overweight, and obese females. AB - BACKGROUND: Little research has been conducted on the heart rate variability (HRV) parameters in late adolescent females. The present study aimed to assess HRV time and frequency domain parameters in overweight and obese late adolescent females. Also to assess any possible correlation between HRV parameters and obesity indices in that particular age group. SUBJECTS AND METHODS: Fifteen minute period of standardized ECG recording was implemented to record HRV time and frequency parameters in 42 normotensive euglycemic female medical students aged (18-21 years); lean (n = 13), overweight (n = 13), and obese (n = 16). For the analysis of results, 2.5-minute data were used. RESULTS: Root mean squares of successive differences between adjacent RR intervals (rMSSD) and high-frequency (HF) power were significantly decreased in overweight and obese late adolescent females. Parameters reflecting sympathetic activity which include low-frequency (LF) power and LF/HF ratio showed significant increase in overweight group. Interestingly, LF power was significantly reduced in obese group while the LF/HF ratio was insignificantly different. No significant correlations were observed between HRV indices and parameters of total or visceral obesity in the study groups. CONCLUSION: HRV indices showed sympathetic hyperactivity in overweight late adolescent females and diminished sympathetic response in matching obese group. Both overweight and obese females showed decreased protective vagal influence on the heart. PMID- 24237670 TI - Insight into the mode of action of 2,4-dichlorophenoxyacetic acid (2,4-D) as an herbicide. AB - 2,4-Dichlorophenoxyacetic acid (2,4-D) was the first synthetic herbicide to be commercially developed and has commonly been used as a broadleaf herbicide for over 60 years. It is a selective herbicide that kills dicots without affecting monocots and mimics natural auxin at the molecular level. Physiological responses of dicots sensitive to auxinic herbicides include abnormal growth, senescence, and plant death. The identification of auxin receptors, auxin transport carriers, transcription factors response to auxin, and cross-talk among phytohormones have shed light on the molecular action mode of 2,4-D as a herbicide. Here, the molecular action mode of 2,4-D is highlighted according to the latest findings, emphasizing the physiological process, perception, and signal transduction under herbicide treatment. PMID- 24237671 TI - In situ ruminal degradation of amino acids and in vitro protein digestibility of undegraded CP of dried distillers' grains with solubles from European ethanol plants. AB - The objectives of this study were to compare the in situ ruminal degradation of CP and amino acids (AAs) of dried distillers' grains with solubles (DDGS), and to estimate intestinal digestibility (ID) of undegradable crude protein (UDP) with the in vitro pepsin-pancreatin solubility of CP (PPS), using either DDGS samples (DDGS-s) or DDGS residues (DDGS-r) obtained after 16 h ruminal incubation. Thirteen samples originating from wheat, corn, barley and blends were studied. Lysine and methionine content of DDGS-s varied from 1.4 to 4.0 and 1.3 to 2.0 g/16 g N, respectively. The milk protein score (MPS) of DDGS-s was low and ranged from 0.36 to 0.51, and lysine and isoleucine were estimated to be the most limiting AAs in DDGS-s and DDGS-r. DDGS-r contained slightly more essential AAs (EAAs) than did the DDGS-s. Rumen degradation after 16 h varied from 44% to 94% for CP, from 39% to 90% for lysine and from 35% to 92% for methionine. Linear regressions showed that the ruminal degradation of individual AAs can be predicted from CP degradation. The PPS of DDGS-s was higher than that of DDGS-r and it varied from 70% to 89% and from 47% to 81%, respectively. There was no significant correlation between the PPS of DDGS-s and PPS of DDGS-r (R 2=0.31). The estimated intestinally absorbable dietary protein (IADP) averaged 21%. Moderate correlation was found between the crude fibre (CF) content and PPS of DDGS-r (R 2=0.43). This study suggests an overestimation of the contribution of UDP of DDGS to digestible protein supply in the duodenum in some currently used protein evaluation systems. More research is required and recommended to assess the intestinal digestibility of AAs from DDGS. PMID- 24237672 TI - In vitro-in vivo study on the effects of plant compounds on rumen fermentation, microbial abundances and methane emissions in goats. AB - Two in vitro and one in vivo experiments were conducted to investigate the effects of a selection of plant compounds on rumen fermentation, microbial concentration and methane emissions in goats. Treatments were: control (no additive), carvacrol (CAR), cinnamaldehyde (CIN), eugenol (EUG), propyl propane thiosulfinate (PTS), propyl propane thiosulfonate (PTSO), diallyl disulfide (DDS), a mixture (40 : 60) of PTS and PTSO (PTS+PTSO), and bromochloromethane (BCM) as positive control with proven antimethanogenic effectiveness. Four doses (40, 80, 160 and 320 ul/l) of the different compounds were incubated in vitro for 24 h in diluted rumen fluid from goats using two diets differing in starch and protein source within the concentrate (Experiment 1).The total gas production was linearly decreased (P<0.012) by all compounds, with the exception of EUG and PTS+PTSO (P>= 0.366). Total volatile fatty-acid (VFA) concentration decreased (P<= 0.018) only with PTS, PTSO and CAR, whereas the acetate:propionate ratio decreased (P<= 0.002) with PTS, PTSO and BCM, and a tendency (P=0.064) was observed for DDS. On the basis of results from Experiment 1, two doses of PTS, CAR, CIN, BCM (160 and 320 ul/l), PTSO (40 and 160 ul/l) and DDS (80 and 320 ul/l) were further tested in vitro for 72 h (Experiment 2). The gas production kinetics were affected (P<= 0.045) by all compounds, and digested NDF (DNDF) after 72 h of incubation was only linearly decreased (P<= 0.004) by CAR and PTS. The addition of all compounds linearly decreased (P<= 0.009) methane production, although the greatest reductions were observed for PTS (up to 96%), DDS (62%) and BCM (95%). No diet-dose interaction was observed. To further test the results obtained in vitro, two groups of 16 adult non-pregnant goats were used to study in vivo the effect of adding PTS (50, 100 and 200 mg/l rumen content per day) and BCM (50, 100 and 160 mg/l rumen content per day) during the 9 days on methane emissions (Experiment 3). The addition of PTS and BCM resulted in linear reductions (33% and 64%, respectively, P<= 0.002) of methane production per unit of dry matter intake, which were lower than the maximum inhibition observed in vitro (87% and 96%, respectively). We conclude that applying the same doses in vivo as in vitro resulted in a proportional lower extent of methane decrease, and that PTS at 200 mg/l rumen content per day has the potential to reduce methane emissions in goats. Whether the reduction in methane emission observed in vivo persists over longer periods of treatments and improves feed conversion efficiency requires further research. PMID- 24237673 TI - Effect of supplementing coconut or krabok oil, rich in medium-chain fatty acids on ruminal fermentation, protozoa and archaeal population of bulls. AB - Medium-chain fatty acids (MCFA), for example, capric acid (C10:0), myristic (C14:0) and lauric (C12:0) acid, have been suggested to decrease rumen archaeal abundance and protozoal numbers. This study aimed to compare the effect of MCFA, either supplied through krabok (KO) or coconut (CO) oil, on rumen fermentation, protozoal counts and archaeal abundance, as well as their diversity and functional organization. KO contains similar amounts of C12:0 as CO (420 and 458 g/kg FA, respectively), but has a higher proportion of C14:0 (464 v. 205 g/kg FA, respectively). Treatments contained 35 g supplemental fat per kg DM: a control diet with tallow (T); a diet with supplemental CO; and a diet with supplemental KO. A 4th treatment consisted of a diet with similar amounts of MCFA (i.e. C10:0+C12:0+C14:0) from CO and KO. To ensure isolipidic diets, extra tallow was supplied in the latter treatment (KO+T). Eight fistulated bulls (two bulls per treatment), fed a total mixed ration predominantly based on cassava chips, rice straw, tomato pomace, rice bran and soybean meal (1.5% of BW), were used. Both KO and CO increased the rumen volatile fatty acids, in particular propionate and decreased acetate proportions. Protozoal numbers were reduced through the supplementation of an MCFA source (CO, KO and KO+T), with the strongest reduction by KO. Quantitative real-time polymerase chain reaction assays based on archaeal primers showed a decrease in abundance of Archaea when supplementing with KO and KO+T compared with T and CO. The denaturing gradient gel electrophoresis profiles of the rumen archaeal population did not result in a grouping of treatments. Richness indices were calculated from the number of DGGE bands, whereas community organization was assessed from the Pareto-Lorenz evenness curves on the basis of DGGE band intensities. KO supplementation (KO and KO+T treatments) increased richness and evenness within the archaeal community. Further research including methane measurements and productive animals should elucidate whether KO could be used as a dietary methane mitigation strategy. PMID- 24237674 TI - Environmental sensitivity differs between rabbit lines selected for reproductive intensity and longevity. AB - To better understand the mechanisms that allow some animals to sustain their productive effort in harsh environmental conditions, rabbit does from two selection lines (LP and V) were housed in normal (NC), nutritional (NF) or heat (HC) challenging environmental conditions from first to third partum. The LP line (n=85) was founded on reproductive longevity criteria by selecting does from commercial farms that had a minimum of 25 partum with more than 7.5 kits born alive per parity. Line V (n=79) was constituted from four specialised maternal lines into a composite synthetic line and then selected by litter size at weaning for 36 generations. Female rabbits in NC and NF environments were housed at normal room temperature (18 degrees C to 24 degrees C) and fed with control [11.6 MJ digestible energy (DE)/kg dry matter (DM)] or low-energy diets (9.1 MJ DE/kg DM). HC does were housed at high room temperatures (25 degrees C to 35 degrees C) and fed the control diet. Female rabbits in the HC and NF environments ingested 11.5% and 6% less DE than NC does, respectively (P<0.05). These differences between environments occurred in both lines, with the differences being higher for LP than for V does (+6%; P<0.05). Milk yield responses followed those of energy intake also being higher for LP does (+21.3 g/day; P<0.05). The environmental conditions did not affect the perirenal fat thickness (PFT), but a genotype by environment interaction was observed. In NC and HC, the PFT was higher for line V (+0.23 and +0.35 mm, respectively; P<0.05) than for LP does, but this was not the case at NF (-0.01 mm). Moreover, the PFT evolution was different between them. In the NC environment, LP does used the accreted PFT in late lactation (-0.29 mm), whereas V does did not (-0.08 mm). Conversely, in the HC environment, LP does showed a flat PFT evolution in late lactation, whereas V does accumulated PFT. In the NF environment, LP and V does had a similar PFT evolution. There was also a litter size reduction for V does of -2.59 kits total born in HC and -1.78 kits total born in NF environments, whereas this was not observed for LP does. The results for LP does indicate a direct use of DE ingested for reproduction with little PFT change, whereas V does actively use the PFT reserves for reproduction. PMID- 24237675 TI - Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets. AB - Ghrelin, the 'hunger' hormone, is an endogenous growth hormone secretagogue that exerts a wide range of physiological functions. Its perinatal presence suggests that ghrelin might be involved in growth and metabolism processes during intrauterine and postnatal life. Intrauterine growth-restricted (IUGR) neonates have altered endocrine and metabolic pathways because of malnutrition during foetal development. These changes might include an altered gastrointestinal presence of ghrelin cells (GCs). As ghrelin is mainly secreted by the stomach, this altered presence might be reflected in its serum concentrations. Small-for gestational age (SGA) pigs appear to be a natural occurring model for IUGR children. Therefore, the first aim of this study was to investigate the presence of gastrointestinal GCs expressing active ghrelin in normal weight (NW) foetal and postnatal piglets compared with their SGA littermates using immunohistochemical analysis in combination with stereological methods. Second, total ghrelin serum concentrations of these piglets were analysed with a porcine radioactive immunoassay. In addition, the growth of the gastric pars fundica in the NW and SGA piglets was analysed stereologically. Corresponding with humans and rats, it was shown that opened- and closed-type immunoreactive GCs are distributed along the entire gastrointestinal tract of the perinatal NW and SGA piglets. However, in contrast to the rat's stomach, the porcine GCs do not disperse from the glandular base to the glandular neck during perinatal development. Furthermore, stereological analysis demonstrated that the NW neonates have a higher amount of gastric cells expressing active ghrelin compared with the SGA piglets that could result in higher milk consumption during the neonatal period. This finding is, however, not reflected in total serum ghrelin levels, which showed no difference between the NW and SGA piglets. Moreover, the stereological volume densities of the fundic layers demonstrate a similar growth pattern in the SGA and NW piglets. PMID- 24237676 TI - Changes in back fat thickness during late gestation predict colostrum yield in sows. AB - Directing protein and energy sources towards lactation is crucial to optimise milk production in sows but how this influences colostrum yield (CY) remains unknown. The aim of this study was to identify associations between CY and the sow's use of nutrient resources. We included 37 sows in the study that were all housed, fed and managed similarly. Parity, back fat change (DeltaBF), CY and performance parameters were measured. We obtained sow serum samples 3 to 4 days before farrowing and at D1 of lactation following overnight fasting. These were analysed for non-esterified fatty acids (NEFA), urea, creatinine, (iso)butyrylcarnitine (C4) and immunoglobulins G (IgG) and A (IgA). The colostrum samples collected 3, 6 and 24 h after the birth of the first piglet were analysed for their nutrient and immunoglobulins content. The technical parameters associated with CY were parity group (a; parities 1 to 3=value 0 v. parities 4 to 7=value 1) and DeltaBF D85-D109 of gestation (mm) (b): CY (g)=4290-842a-113b. (R 2=0.41, P<0.001). The gestation length (P<0.001) and the DeltaBF between D109 and D1 of lactation (P=0.050) were identified as possible underlying factors of the parity group. The metabolic parameters associated with CY were C4 at 3 to 4 days before farrowing (a), and 10logC4 (b) and 10logNEFA (c) at D1 of lactation: CY (g)=3582-1604a+1007b-922c (R 2=0.39, P=0.001). The colostrum composition was independent of CY. The negative association between CY and DeltaBF D85-D109 of gestation could not be further explained based on our data. Sows that were catabolic 1 week prior to farrowing seemed unable to produce colostrum to their full potential. This was especially the case for sows with parities 4 to 7, although they had a similar feed intake, litter birth weight and colostrum composition compared with parities 1 to 3 sows. In conclusion, this study showed that parity and the use of body fat and protein reserves during late gestation were associated with CY, indicating that proper management of the sow's body condition during late gestation could optimise the intrinsic capacity of the sow's CY. PMID- 24237677 TI - Mathematical approaches to detect low concentrations in progesterone profiles. AB - There is a general need for higher objectivity and accuracy in describing the physiological fertility performance of dairy cows. To develop the alternative meaningful starting points for the selection of genetically superior dairy cows, this study focused on the detection of low progesterone concentrations, which are indicative of estrus events. Three mathematical approaches were used: one based on the exponentially weighted moving average control chart, and two threshold methods, which were developed in-house. Data were collected from one data set that included 97 insemination data of first-lactating Holstein dairy cows, and a second set that included 160 inseminations of primiparous and multiparous Holstein dairy cows. On the basis of these 2 data sets, and using a threshold of 1.2 ng progesterone/ml skimmed milk, the sensitivity of the 3 models was high and ranged between 100% and 93.13%, with an error rate between 4% and 22.17%. The specificity varied between 97.92% and 99.93%. The average concentration levels of true-positive-detected progesterone measures were low and ranged between 0.18 and 0.28 ng progesterone/ml skimmed milk (first data set) and 0.21 to 0.26 ng progesterone/ml skimmed milk (second data set). False-positive-detected low progesterone concentrations during estrus events were closely related to progesterone values around the 1.2 ng progesterone/ml skimmed milk threshold and the detecting rules of the control chart. Thus, we suggest that a threshold of 0.8 ng progesterone/ml skimmed milk is indicative for luteal activity in defatted foremilk. By means of the three methods used, the detection of low progesterone concentrations was possible and it can be assumed that this is a good starting point for further studies (such as interval calculation) in this area. PMID- 24237678 TI - Infrared thermography--a non-invasive tool to evaluate thermal status of neonatal pigs based on surface temperature. AB - Hypothermia is a major cause of mortality in neonatal pigs. Infrared (IR) thermography is a promising non-invasive method to assess thermal status, but has not been evaluated for use on neonatal pigs from birth. The aim of this study was to evaluate the application of IR thermography as a non-invasive tool to estimate body temperature and assess the thermal status in newborn pigs by (1) estimating the relationship between surface temperature and rectal temperature (RT) in neonatal pigs; and (2) estimating the influence of air temperature (AT), birth weight and the time from birth on the relationship between surface temperature and RT. The method was evaluated on the basis of 1695 thermograms and 915 RTs on 91 neonatal pigs born in loose farrowing pens with floor heating at 34 degrees C, and three different ATs (15 degrees C, 20 degrees C and 25 degrees C). Full-body thermograms of the back and the side of the pigs and RT were acquired at 11 sampling times between birth and 48 h after birth. The maximum (IRmax), minimum, average of the full body and ear minimum IR surface temperatures were derived from the thermograms. IRmax had the highest correlation with RT (0.82) and was therefore used in the statistical analysis. The relation of RT by IRmax depended on time at: 0 h (slope: 0.20 degrees C, P<0.001), 0.25 h (slope: 0.42 degrees C, P<0.01), and 0.5 and 1 h after birth (slope: 0.68 degrees C, P<0.001). After the 1st hour (1.5 to 48 h) the relation of RT by IRmax was no longer affected by time (slope: 0.63 degrees C, P<0.001). The agreement between RT and IRmax was improved (P<0.001) after the 1st hour (RT-IRmax 0 to 1 h: 2.02 (1.44) degrees C; 1.5 to 48 h: 0.95 (0.85) degrees C). IRmax below 30 degrees C was indicative of piglets having RT<32 degrees C (91.3%). The location of IRmax was identified predominantly at the base of the ears (27/50), other sites in the region of the head (12/50) and the axilla area (8/50). There was a small but significant effect of the angle as IRmax_side-IRmax_back: mean 0.20 degrees C (P<0.001). On the basis of the low difference between IRmax from back and side view thermograms, and the location of IRmax, the angle seems less important and thus the method has the potential to be used without the need for manual restraint of the pigs. On the basis of the results of this study, we propose that IRmax temperature from full-body thermograms has implication as a valid tool to assess the thermal status in neonatal piglets but not as an identical substitute for RT. PMID- 24237679 TI - Effect of production system before the finishing period on carcass, meat and fat qualities of beef. AB - Twenty Gascon young bulls that had been reared either in intensive conditions (INT) (n=10) with early weaning at 3 to 4 months, or in a traditional extensive (EXT) system (n=10) with weaning at 7 months, were subjected to the same conditions during the 145-day finishing period. Production system before the finishing period did not affect conformation, dressing percentage or morphology of the carcass; nevertheless, tissue composition differed somewhat between the two groups. Display had a stronger effect on meat colour than did production system. Percentage of myoglobin was highest in INT (P<= 0.001), although meat texture and sensory quality did not differ between rearing conditions. EXT animals had darker, more yellow fat, a higher percentage of n-3 fatty acids (P<= 0.001), a lower percentage of saturated fatty acids (P<= 0.05) and a lower n-6/n 3 index (P<= 0.001) than did the INT-reared animals. Production system before the fattening period might modify some of the characteristics of commercial beef, especially those associated with fat. PMID- 24237681 TI - The natural history of pregnancies with a diagnosis of trisomy 18 or trisomy 13; a retrospective case series. AB - BACKGROUND: Trisomy 18 (T18) and trisomy 13 (T13) are the second and third commonest autosomal aneuploidy syndromes respectively. While specific aspects of affected pregnancies have been documented in the literature, few studies document the overall natural history of the trisomies. This study aimed to examine the natural history (including diagnosis, pregnancy outcome, complications and survival) of T18 and T13 pregnancies in a setting where termination of pregnancy for fetal abnormality is not available. METHODS: Cases were identified using birth registers, labour ward records, annual reports, medical records, ultrasound reports and reports from prenatal genetic testing. All identified T18 and T13 pregnancies in the study region from 2001 to 2012 were included. Individual chart reviews were performed for each case. Data were analysed using SPSS Version 20. RESULTS: Forty-six T18 and twenty-four T13 pregnancies were identified. Most T18 cases (65%) were diagnosed prenatally, while only one third (33%) of T13 cases were prenatally diagnosed. Only three T18 pregnancies and one T13 pregnancy were electively terminated. A proportion of undiagnosed infants were delivered by emergency caesarean section. 48% (T18) and 46% (T13) infants survived following birth, for a median of 1.5 days (T18) and 7 days (T13). One T13 infant is currently alive over one year of age. CONCLUSIONS: This large series provides information for professionals and women regarding the natural histories of trisomies 18 and 13. These pregnancies can go undiagnosed antenatally without routine anomaly scanning. While many fetuses die in-utero, postnatal survival is possible. PMID- 24237682 TI - Do malaria vector control measures impact disease-related behaviour and knowledge? Evidence from a large-scale larviciding intervention in Tanzania. AB - BACKGROUND: Recent efforts of accelerated malaria control towards the long-term goal of elimination had significant impacts in reducing malaria transmission. While these efforts need to be sustained over time, a scenario of low transmission could bring about changes in individual disease risk perception, hindering adherence to protective measures, and affecting disease-related knowledge. The goal of this study was to investigate the potential impact of a successful malaria vector control intervention on bed net usage and malaria related knowledge. METHODS: Dar es Salaam's Urban Malaria Control Program was launched in 2004 with the aim of developing a sustainable larviciding intervention. Larviciding was scaled-up using a stepped-wedge design. Cross sectional and longitudinal data were collected using a randomized cluster sampling design (2004-2008). Prevalence ratios (PR) for the effect of the larviciding intervention on bed net usage (N = 64,537) and household heads' knowledge of malaria symptoms and transmission (N = 11,254) were obtained from random effects regression models. RESULTS: The probability that individuals targeted by larviciding had used a bed net was reduced by 5% as compared to those in non-intervention areas (PR = 0.95; 95% credible intervals (CrI): 0.94-0.97) and the magnitude of this effect increased with time. Larviciding also led to a decline in household heads' knowledge of malaria symptoms (PR = 0.88; 95% CrI: 0.83-0.92) but no evidence of effect on knowledge of malaria transmission was found. CONCLUSION: Successful control interventions could bring about further challenges to sustaining gains in reducing malaria transmission if not accompanied by strategies to avoid changes in individual knowledge and behaviour. This study points to two major research gaps. First, there is an urgent need to gather more evidence on the extent to which countries that have achieved significant decline in malaria transmission are also observing changes in individual behaviour and knowledge. Second, multidisciplinary assessments that combine quantitative and qualitative data, utilizing theories of health behaviour and theories of knowledge, are needed to optimize efforts of national malaria control programmes, and ultimately contribute to sustained reduction in malaria transmission. PMID- 24237683 TI - Stability scheme of ZnO-thin film resistive switching memory: influence of defects by controllable oxygen pressure ratio. AB - We report a stability scheme of resistive switching devices based on ZnO films deposited by radio frequency (RF) sputtering process at different oxygen pressure ratios. I-V measurements and statistical results indicate that the operating stability of ZnO resistive random access memory (ReRAM) devices is highly dependent on oxygen conditions. Data indicates that the ZnO film ReRAM device fabricated at 10% O2 pressure ratio exhibits the best performance. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) of ZnO at different O2 pressure ratios were investigated to reflect influence of structure to the stable switching behaviors. In addition, PL and XPS results were measured to investigate the different charge states triggered in ZnO by oxygen vacancies, which affect the stability of the switching behavior. PMID- 24237684 TI - Rosen's (M,R) system in process algebra. AB - BACKGROUND: Robert Rosen's Metabolism-Replacement, or (M,R), system can be represented as a compact network structure with a single source and three products derived from that source in three consecutive reactions. (M,R) has been claimed to be non-reducible to its components and algorithmically non-computable, in the sense of not being evaluable as a function by a Turing machine. If (M,R) like structures are present in real biological networks, this suggests that many biological networks will be non-computable, with implications for those branches of systems biology that rely on in silico modelling for predictive purposes. RESULTS: We instantiate (M,R) using the process algebra Bio-PEPA, and discuss the extent to which our model represents a true realization of (M,R). We observe that under some starting conditions and parameter values, stable states can be achieved. Although formal demonstration of algorithmic computability remains elusive for (M,R), we discuss the extent to which our Bio-PEPA representation of (M,R) allows us to sidestep Rosen's fundamental objections to computational systems biology. CONCLUSIONS: We argue that the behaviour of (M,R) in Bio-PEPA shows life-like properties. PMID- 24237685 TI - Prolonged non-survival in PICU: does a do-not-attempt-resuscitation order matter. AB - BACKGROUND: Etiologies of pediatric intensive care unit (PICU) mortality are diverse. This study aimed to investigate the pattern of PICU mortality in a regional trauma center, and explore factors associated with prolonged non survival. METHODS: Demographic data of all PICU deaths in a regional trauma center were analyzed. Factors associated with prolonged nonsurvival (length of stay) were investigated with univariate log rank and multivariate Cox-Regression forward stepwise tests. RESULTS: There were 88 deaths (males 61%; infants 23%) over 10 years (median PICU stay = 3.5 days, interquartile range: 1 and 11 days). The mean annual mortality rate of PICU admissions was 5.8%. Septicemia with gram positive, gram negative and fungal pathogens were present in 13 (16%), 13 (16%) and 4 (5%) of these patients, respectively. Viruses were isolated in 25 patients (28%). Ninety percent of these 88 patients were ventilated, 75% required inotropes, 92% received broad spectrum antibiotic coverage, 32% received systemic corticosteroids, 56% required blood transfusion and 39% received anticonvulsants. Thirty nine patients (44%) had a DNAR (Do-Not-Attempt-Resuscitation) order with their deaths at the PICU. Comparing with non-trauma category, trauma patients had higher mortality score, no premorbid disease, suffered asystole preceding PICU admission and subsequent brain death. Oncologic conditions were the most prevalent diagnosis in the non-trauma category. There was no gunshot or asthma death in this series. Prolonged non-survival was significantly associated with DNAR, fungal infections, and mechanical ventilation but negatively associated with bacteremia. CONCLUSIONS: Death in the PICU is a heterogeneous event that involves infants and children. Resuscitation was not attempted at the time of their deaths in nearly half of the patients in honor of parents' wishes. Parents often make DNAR decision when medical futility becomes evident. They could be reassured that DNAR did not mean "abandoning" care. Instead, DNAR patients had prolonged PICU stay and received the same level of PICU supports as patients who did not respond to cardiopulmonary resuscitation. PMID- 24237686 TI - Fungal biology in Brazil. PMID- 24237687 TI - Epicardial/endocardial sinus node ablation after failed endocardial ablation for the treatment of inappropriate sinus tachycardia. AB - INTRODUCTION: Success of endocardial sinus node (SN) ablation for refractory inappropriate sinus tachycardia (IST) is limited by the epicardial location of the SN and potential damage to the phrenic nerve (PN). An epicardial approach may overcome these limitations. METHODS AND RESULTS: IST patients who failed endocardial ablation underwent an epicardial approach. Percutaneous pericardial access was obtained with a double wire technique for PN protection (i.e., with a balloon catheter), if needed. Earliest sinus activation was mapped and ablated with remapping for changes in P-wave morphology or sinus rate. The endpoint was total SN ablation (patients with atrial pacing [AP]); otherwise the target was a >25% decrease in sinus rate and inversion of P-wave axis. Five patients (all female, age 36 +/- 4 years) underwent ablation. Two had prior AP, and 1 elected to have SN ablation and pacemaker during the same procedure. Three had prior endocardial ablation limited by PN proximity. Baseline sinus rate was 119 +/- 20 bpm. After 35.2 +/- 21.3 lesions (22.4 +/- 21.7 epicardial, 12.8 +/- 21.3 endocardial), 4 were in junctional rhythm, 1 in atrial rhythm at 90 bpm. This latter patient had symptom recurrence and underwent combined minimally invasive surgical/catheter SN cryoablation. Atrial tachycardia subsequently occurred and was successfully ablated. The only significant complication was pericarditis (3 patients). At last follow-up (30.4 +/- 18.4 months), all had symptom resolution. Two were AP >99%, 1 was AP 54%. Two remain in ectopic atrial rhythm with controlled rates. CONCLUSIONS: Combined epicardial/endocardial SN ablation is a viable approach for patients with severely symptomatic IST after a failed endocardial attempt. PMID- 24237688 TI - Comparison of isolation rate of Borrelia burgdorferi sensu lato in two different culture media, MKP and BSK-H. AB - The aim of the study was to evaluate two culture media for Borrelia burgdorferi sensu lato isolation from a 5 * 2 * 2 mm skin biopsy that was dissected into two pieces and inoculated into modified Kelly-Pettenkofer (MKP) and Barbour-Stoenner Kelly-H (BSK-H) medium. Samples were incubated at 33 degrees C for up to 9 weeks. Borrelia species was determined by MluI-restriction of whole genome or by MseI restriction of PCR product. We determined the proportion of isolation rate, 'slow growers', contaminated specimens and Borrelia species in the two media. In each of the two media 235 skin specimens were cultivated. We found 90/470 (19.1%) contaminated cultures (BSK-H 67/235, 28.5%; MKP 23/235, 9.8%; p <0.0001). Borrelia growth was ascertained in 59/235 (25.1%) BSK-H and 102/235 (43.4%) MKP cultures (p <0.0001); the corresponding values for non-contaminated cultures were 59/168 (35.1%) and 102/212 (48.1%); (p 0.003). Fourteen specimens were positive only in BSK-H, 57 solely in MKP, and 43 in both culture media. Slow growth was present in 8/59 (13.6%) BSK-H and in 4/98 (4.1%) MKP positive cultures (p 0.019). Borrelia afzelii was identified in 44/51 (86.3%) BSK-H and in 88/98 (89.8%) MKP culture-positive samples; the corresponding findings for Boreelia garinii and B. burgdorferi sensu stricto were 6/51 (11.8%) and 9/98 (9.2%), and 1/51 (1.9%) and 1/98 (1.0%), for BSK-H and MKP, respectively. Comparison of MKP and BSK-H medium for Borrelia culturing from skin specimens of European patients with erythema migrans revealed the advantage of MKP over BSK-H. PMID- 24237689 TI - Behavioural activation interventions for depressed individuals with a chronic physical illness: a systematic review protocol. AB - BACKGROUND: Depression is common in people with chronic physical illness and is associated with worse medical outcomes. Cognitive behavioural therapy and problem solving improve depression, although usually have small to moderate effects among people with chronic physical illness. Behavioural activation interventions for depression, which aim to increase positive reinforcement from the environment by encouraging individuals to increase pleasant/rewarding activities, have been reported to be equivalent to cognitive behavioural therapy. However, the effectiveness of behavioural activation interventions for depression in individuals with chronic physical illness is unclear. The aims of this systematic review are to identify the extent to which different forms of behavioural activation have been used as a treatment for depression in this population, examine the effectiveness of the interventions, and identify any adaptations which have been made specifically to the interventions for individuals with a range of chronic physical illnesses. METHODS/DESIGN: Electronic databases will be systematically searched using terms relevant to behavioural activation and depression, and the subset of studies in people with chronic physical illnesses will be identified by manual searching. References and citations of eligible studies will be searched and experts in this field will be contacted to identify additional papers. All study designs will be included in this review to allow for a more extensive identification of the extent of different forms of behavioural activation interventions. The different forms of behavioural activation and the specific chronic physical health conditions for which this intervention has been used will be reviewed narratively. For the effectiveness of the interventions, if sufficient randomised controlled trials have been undertaken the results will be meta-analysed. Non-randomised studies will be narratively synthesised and adaptations to the interventions will also be narratively reviewed. DISCUSSION: The findings will inform the design, development and subsequent evaluation of a behavioural activation intervention for depression in people with a chronic physical illness. PROSPERO registration number: CRD42013004500. PMID- 24237690 TI - Bio-integrated organic synthesis in industry: biocatalytic breakthroughs, industrial processes, emerging fields. PMID- 24237691 TI - Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. AB - BACKGROUND: Preclinical and clinical trials suggest that yohimbine may augment extinction learning without significant side effects. However, previous clinical trials have only examined adults with specific phobias. Yohimbine has not yet been investigated in the augmentation of exposure therapy for other anxiety disorders. METHODS: Adults (n = 40) with a DSM-IV diagnosis of social anxiety disorder were randomized to placebo or yohimbine HCl (10.8 mg) 1 hour before each of four exposure sessions. Outcome measures were collected at baseline, each treatment session, posttreatment, and 1-month follow-up. RESULTS: Yohimbine was well tolerated. Yohimbine augmentation, relative to placebo augmentation, resulted in faster improvement and better outcomes on self-report measures of social anxiety disorder severity (Liebowitz Social Anxiety Scale, d = .53) and depressed mood severity (Beck Depression Inventory, d = .37) but not on the clinician-rated measures (Clinical Global Impressions-Severity Scale, d = .09; Clinical Global Impressions-Improvement Scale, d = .25). Between-group differences on the Liebowitz Social Anxiety Scale were moderated by the level of fear reported at the end of an exposure exercise (end fear), such that the advantage of yohimbine over placebo was only evident among patients who reported low end fear. CONCLUSIONS: The results provide moderate support for yohimbine as a therapeutic augmentation strategy for exposure therapy in social anxiety disorder, one that may be especially effective when coupled with successful exposure experiences. Beneficial effects for yohimbine were readily evident for self-report measures but not for clinician-rated outcomes of social anxiety severity and improvement. PMID- 24237692 TI - Candida albicans: adapting to succeed. AB - In this issue of Cell Host & Microbe, Lu et al. (2013) report on the redundancy of signaling pathways controlling Candida albicans filamentation and pathogenicity. In the process, they provide important insight into how this normal commensal of humans adapts to different host microenvironments to become a highly successful opportunistic pathogen. PMID- 24237693 TI - The lectin ERGIC-53 goes viral. AB - The biosynthesis of fusion-competent envelope glycoproteins (GPs) is a crucial step in productive viral infection. In this issue, Klaus et al. (2013) identify the cargo receptor endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53) as a binding partner for viral GPs and a crucial cellular factor required for infectious virus production. PMID- 24237694 TI - TLR5 stops commensals in their tracks. AB - IgA antibodies help maintain intestinal immune homeostasis with resident commensal species; however, the precise mechanisms regulating IgA induction and the epitopes recognized by these antibodies remain incompletely understood. In this issue of Cell Host & Microbe, Tyler et al. (2013) demonstrate that TLR5 dependent induction of anti-flagellin antibodies prevents commensal association with the intestinal mucosa by limiting bacterial motility. PMID- 24237695 TI - Inflammasome-microbiota interplay in host physiologies. AB - Host defense responses against microbes are most often thought of in terms of effectors of microbial destruction. However, recent evidence demonstrates that the more complex interactions between the microbiota and innate immune mechanisms, such as the inflammasome-mediated response, cannot be readily explained within just the traditional paradigms of microbial killing mechanisms. In this review, the concepts of both resistance and tolerance are applied to inflammasome-microbiota interactions, and the various physiological consequences of this interplay, including roles in inflammation, tissue repair, tumorigenesis, and metabolism, are discussed. PMID- 24237696 TI - Synergistic regulation of hyphal elongation by hypoxia, CO(2), and nutrient conditions controls the virulence of Candida albicans. AB - Candida albicans reversibly switches between yeast and hyphal morphologies, with hyphae being associated with virulence. Hyphal initiation and maintenance depend on host environment sensing. Hyphal maintenance in vitro requires chromatin remodeling of hypha-specific gene promoters, although disrupting chromatin remodeling does not disrupt C. albicans hyphal elongation and virulence during invasive infection. We find that the combination of hypoxia and high CO2, but neither condition alone, maintains hyphal elongation, even in mutants lacking the nutrient-responsive chromatin-remodeling pathway. Ume6, the transcriptional activator of hypha-specific genes, is stabilized via regulation by Ofd1, a prolyl hydroxylase family member inhibited by hypoxia, and by an uncharacterized pathway that senses high CO2. Virulence and hyphal elongation in vivo are attenuated only when the parallelly acting Ume6 stabilization and chromatin-remodeling pathways are both blocked. The evolution of redundant signaling pathways allowing C. albicans to adapt to varied host environments may explain this commensal's success as a pathogen. PMID- 24237697 TI - Type I interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection. AB - Several enveloped viruses exploit host pathways, such as the cellular endosomal sorting complex required for transport (ESCRT) machinery, for their assembly and release. The influenza A virus (IAV) matrix protein binds to the ESCRT-I complex, although the involvement of early ESCRT proteins such as Tsg101 in IAV trafficking remain to be established. We find that Tsg101 can facilitate IAV trafficking, but this is effectively restricted by the interferon (IFN) stimulated protein ISG15. Cytosol from type I IFN-treated cells abolished IAV hemagglutinin (HA) transport to the cell surface in infected semi-intact cells. This inhibition required Tsg101 and could be relieved with deISGylases. Tsg101 is itself ISGylated in IFN-treated cells. Upon infection, intact Tsg101-deficient cells obtained by CRISPR-Cas9 genome editing were defective in the surface display of HA and for infectious virion release. These data support the IFN induced generation of a Tsg101- and ISG15-dependent checkpoint in the secretory pathway that compromises influenza virus release. PMID- 24237698 TI - The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles. AB - Arenaviruses and hantaviruses cause severe human disease. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53), a cargo receptor required for glycoprotein trafficking within the early exocytic pathway, associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into virions. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP containing virus particles form but are noninfectious, due in part to their inability to attach to host cells. Thus, we have identified a class of pathogen derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families. PMID- 24237699 TI - HIV-1 induces the formation of stable microtubules to enhance early infection. AB - Stable microtubule (MT) subsets form distinct networks from dynamic MTs and acquire distinguishing posttranslational modifications, notably detyrosination and acetylation. Acting as specialized tracks for vesicle and macromolecular transport, their formation is regulated by the end-binding protein EB1, which recruits proteins that stabilize MTs. We show that HIV-1 induces the formation of acetylated and detyrosinated stable MTs early in infection. Although the MT depolymerizing agent nocodazole affected dynamic MTs, HIV-1 particles localized to nocodazole-resistant stable MTs, and infection was minimally affected. EB1 depletion or expression of an EB1 carboxy-terminal fragment that acts as a dominant-negative inhibitor of MT stabilization prevented HIV-1-induced stable MT formation and suppressed early viral infection. Furthermore, we show that the HIV 1 matrix protein targets the EB1-binding protein Kif4 to induce MT stabilization. Our findings illustrate how specialized MT-binding proteins mediate MT stabilization by HIV-1 and the importance of stable MT subsets in viral infection. PMID- 24237700 TI - Modeling virus- and antibody-specific factors to predict human immunodeficiency virus neutralization efficiency. AB - Efforts to prevent human immunodeficiency virus type 1 (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies. PMID- 24237701 TI - Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. AB - Microbial exposure following birth profoundly impacts mammalian immune system development. Microbiota alterations are associated with increased incidence of allergic and autoimmune disorders with elevated serum IgE as a hallmark. The previously reported abnormally high serum IgE levels in germ-free mice suggests that immunoregulatory signals from microbiota are required to control basal IgE levels. We report that germ-free mice and those with low-diversity microbiota develop elevated serum IgE levels in early life. B cells in neonatal germ-free mice undergo isotype switching to IgE at mucosal sites in a CD4 T-cell- and IL-4 dependent manner. A critical level of microbial diversity following birth is required in order to inhibit IgE induction. Elevated IgE levels in germ-free mice lead to increased mast-cell-surface-bound IgE and exaggerated oral-induced systemic anaphylaxis. Thus, appropriate intestinal microbial stimuli during early life are critical for inducing an immunoregulatory network that protects from induction of IgE at mucosal sites. PMID- 24237702 TI - Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. AB - Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis. PMID- 24237703 TI - Microbial modulation of energy availability in the colon regulates intestinal transit. AB - Gut microbiota contribute to host metabolic efficiency by increasing energy availability through the fermentation of dietary fiber and production of short chain fatty acids (SCFAs) in the colon. SCFAs are proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, which stimulates insulin secretion (incretin response) and inhibits gastric emptying. We find that germ free (GF) and antibiotic-treated mice, which have severely reduced SCFA levels, have increased basal GLP-1 levels in the plasma and increased Gcg expression in the colon. Increasing energy supply, either through colonization with polysaccharide-fermenting bacteria or through diet, suppressed colonic Gcg expression in GF mice. Increased GLP-1 levels in GF mice did not improve the incretin response but instead slowed intestinal transit. Thus, microbiota regulate the basal levels of GLP-1, and increasing these levels may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption. PMID- 24237704 TI - Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. AB - Nuclear sensing of viral DNA has emerged as an essential step in innate immune responses against herpesviruses. Here, we provide mechanistic insight into host recognition of human cytomegalovirus (HCMV) and subsequent immune evasion by this prominent DNA virus. We establish that the interferon-inducible protein IFI16 acts as a nuclear DNA sensor following HCMV infection, binding viral DNA and triggering expression of antiviral cytokines via the STING-TBK1-IRF3 signaling pathway. The HCMV tegument protein pUL83 inhibits this response by interacting with the IFI16 pyrin domain, blocking its oligomerization upon DNA sensing and subsequent immune signals. pUL83 disrupts IFI16 by concerted action of its N- and C-terminal domains, in which an evolutionarily conserved N-terminal pyrin association domain (PAD) binds IFI16. Additionally, phosphorylation of the N terminal domain modulates pUL83-mediated inhibition of pyrin aggregation. Collectively, our data elucidate the interplay between host DNA sensing and HCMV immune evasion, providing targets for restoring antiviral immunity. PMID- 24237705 TI - Kin-bias, breeding site selection and female fitness in a cannibalistic Neotropical frog. AB - Resource availability influences sexual selection within populations and determines whether behaviours such as territoriality or resource sharing are adaptive. In Thoropa taophora, a frog endemic to the Atlantic Coastal Rainforest of Brazil, males compete for and defend limited breeding sites while females often share breeding sites with other females; however, sharing breeding sites may involve costs due to cannibalism by conspecific tadpoles. We studied a breeding population of T. taophora to determine (i) whether this species exhibits polygynous mating involving female choice for territorial males and limited breeding resources; (ii) whether limited breeding resources create the potential for male-male cooperation in defence of neighbouring territories; and (iii) whether females sharing breeding sites exhibit kin-biased breeding site choice, possibly driven by fitness losses due to cannibalism among offspring of females sharing sites. We used microsatellites to reconstruct parentage and quantify relatedness at eight breeding sites in our focal population, where these sites are scarce, and in a second population, where sites are abundant. We found that at localities where the appropriate sites for reproduction are spatially limited, the mating system for this species is polygynous, with typically two females sharing a breeding site with a male. We also found that females exhibit negative kin-bias in their choice of breeding sites, potentially to maximize their inclusive fitness by avoiding tadpole cannibalism of highly related kin. Our results indicate that male territorial defence and female site sharing are likely important components of this mating system, and we propose that kinship-dependent avoidance in mating strategies may be more general than previously realized. PMID- 24237706 TI - The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high osmolarity glycerol signaling pathways. AB - Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (DeltaFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. DeltaFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (DeltaFgRLM1) showed increased sensitivity to cell wall damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. PMID- 24237707 TI - Investigating the effects of conscientiousness on daily stress, affect and physical symptom processes: a daily diary study. AB - OBJECTIVES: Higher conscientiousness (C) predicts better health outcomes. Recent research suggests that stress may play an important role in explaining this relationship. The current study aimed to establish whether C moderates the relationship between daily hassle appraisals, daily affect, and physical symptoms. DESIGN AND METHODS: A daily diary design was used, where participants (N = 103) completed a baseline measure of C followed by a 14-day daily diary, providing daily details of hassles (primary and secondary appraisals) experienced as well as positive and negative affect and physical symptoms. RESULTS: Hierarchical linear modelling revealed that Total C (as well as two facets of C: Order and Industriousness) moderated the relationship between stress appraisals and positive affect. Specifically, the negative association between the daily appraisal of hassles as stressful (i.e., where perceived demands outweighed perceived resources) and positive affect was stronger for lower and average levels of C, Order, and Industriousness. No significant moderated effects were found for negative affect or physical symptoms. The Order facet was also found to be an important factor predicting attrition. CONCLUSIONS: The current study provided evidence that C and two of its facets can moderate the relationship between hassle appraisal and positive affect. C may exert part of its influence on health by modifying the effects of daily stressors. STATEMENT OF CONTRIBUTION: What is already known on this subject? Conscientiousness has a significant positive effect on longevity and health status. While the performance of health behaviours may partially account for this relationship, evidence suggests that it does not fully mediate the effect. Research has begun to look at stress as a possible additional explanatory variable, and there is evidence that Conscientiousness moderates the relationship between stress and health behaviours. What does this study add? Shows that Conscientiousness and two of its facets (Order and Industriousness) moderate the relationship between hassle appraisal and positive affect. Highlights the importance of studying lower order facets of personality in health research. Suggests that Conscientiousness may exert part of its influence on health by modifying the effects of daily stressors. PMID- 24237708 TI - The effect of RFC G80A polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms. AB - INTRODUCTION: The association between the risk of acute lymphoblastic leukemia (ALL) in children and enzymes involved in the folate metabolism has been under investigation lately. The reduced folate carrier gene (RFC) encodes reduced folate carrier, a protein that transports into the cell both folate and methotrexate, a commonly used chemotherapeutic drug, has been proved polymorphic at position 80 (G->A). The role of this polymorphism in childhood ALL and its interaction with other enzymes of the folate metabolic pathway, including MTHFR, has been examined in different populations with diverse results. METHODS: In the present case-control study, 35 children with ALL and 48 healthy adult blood donors, all originating from the island of Crete (Greece), were screened for the presence of the RFC G80A polymorphism, using PCR/RFLP techniques. The effect on ALL risk and methotrexate-induced toxicities, along with the role of gene-gene interactions in our population, were examined. RESULTS: No significant association was observed between the RFC G80A genotypes and either the development of ALL or the presence of adverse events. However, a significant association was detected between the MTHFR A1298C/ RFC G80A genotype and a nonpredisposition for ALL (P = 0.035). CONCLUSION: This study suggests that gene gene interactions in childhood ALL may be of prognostic value in our population. PMID- 24237710 TI - Diversity characterization and association analysis of agronomic traits in a Chinese peanut (Arachis hypogaea L.) mini-core collection. AB - Association mapping is a powerful approach for exploring the molecular basis of phenotypic variations in plants. A peanut (Arachis hypogaea L.) mini-core collection in China comprising 298 accessions was genotyped using 109 simple sequence repeat (SSR) markers, which identified 554 SSR alleles and phenotyped for 15 agronomic traits in three different environments, exhibiting abundant genetic and phenotypic diversity within the panel. A model-based structure analysis assigned all accessions to three groups. Most of the accessions had the relative kinship of less than 0.05, indicating that there were no or weak relationships between accessions of the mini-core collection. For 15 agronomic traits in the peanut panel, generally the Q + K model exhibited the best performance to eliminate the false associated positives compared to the Q model and the general linear model-simple model. In total, 89 SSR alleles were identified to be associated with 15 agronomic traits of three environments by the Q + K model-based association analysis. Of these, eight alleles were repeatedly detected in two or three environments, and 15 alleles were commonly detected to be associated with multiple agronomic traits. Simple sequence repeat allelic effects confirmed significant differences between different genotypes of these repeatedly detected markers. Our results demonstrate the great potential of integrating the association analysis and marker-assisted breeding by utilizing the peanut mini-core collection. PMID- 24237709 TI - Increased leg blood flow and improved femoral artery shear patterns in metabolic syndrome after a diet and exercise programme. AB - BACKGROUND: Altered vascular shear profiles may contribute to the development of atherosclerosis. Physical activity promotes anti-atherogenic shear patterns, resulting in reduced cardiovascular disease risk. Adults with metabolic syndrome (MetSyn) are at increased risk of developing atherosclerosis and cardiovascular disease. Thus, we hypothesized that conduit artery antegrade shear rate (ASR) would increase and retrograde shear rate (RSR) and oscillatory shear indices (OSI) would decrease in MetSyn patients (n = 16, 51 +/- 2 years) after participation in a diet and exercise programme (DEP). METHODS: Blood flow (Doppler ultrasound, brachial and femoral arteries) was measured, and shear rates were calculated in MetSyn patients before and after 12 weeks of DEP participation. In addition, plasma samples were collected to measure atherogenic markers. RESULTS: Diet and exercise programme participation increased resting leg blood flow and femoral artery ASR (P <= 0.05), and tended to decrease OSI (P = 0.09); RSR did not change (P>0.05). No changes in resting arm blood flow or ASR were observed (P>0.05), and both RSR and OSI increased after participation (P<=0.05). DEP participation reduced plasma vascular cell adhesion molecule(VCAM) 1 (P = 0.03), with a trend for reduced intercellular cell adhesion molecule(ICAM) 1 (P = 0.09) (i.e. atherogenic markers). CONCLUSION: Modest changes in diet and physical activity result in limb-specific improvements in vascular shear profiles and reduced systemic markers of atherosclerotic risk in MetSyn patients. These data provide novel physiologic insight into adaptations that may limit the progression of atherosclerosis in patients with MetSyn. PMID- 24237711 TI - Calculating risks: the power and pitfalls of registry data. AB - COMMENTARY ON: Schoenfeld AJ, Carey PA, Cleveland AW III, et al. Patient factors, comorbidities, and surgical characteristics that increase mortality and complication risk after spinal arthrodesis: a prognostic study based on 5,887 patients. Spine J 2013;13:1171-79 (in this issue). PMID- 24237712 TI - End-plate measurements as early markers of disc degeneration and herniation. PMID- 24237713 TI - Fouladi responds. PMID- 24237714 TI - Comparison of encapsulated versus nonencapsulated (14) C-urea breath test for the detection of Helicobacter pylori infection: a scintigraphy study. AB - BACKGROUND AND AIMS: (14) C-urea breath test ((14) C-UBT) is considered as "gold standard" for detection of active gastric H. pylori infection. However, till date no comparative study using encapsulated and non-encapsulated (14) C-UBT protocols has been conducted in same subjects in identical conditions. We monitored gastric fate of capsule containing (14) C-urea with real time display and compared sensitivities of these protocols at different time points of breath collection. METHODS: Non-encapsulated (14) C-UBT was performed using 74 kBq of (14) C-urea in 100 dyspeptic patients by collecting breath samples at 10, 15 and 20 minutes. Thereafter, within 2 days a gelatin capsule containing (14) C-urea along with 6.0 MBq of (99m) Tc-diethylene triamine penta-acetic acid was administered to each patient for real time display of capsule movement and its fate in gastrointestinal tract by gamma camera. Simultaneously, breath samples were collected for (14) CO2 measurement during image acquisition. RESULTS: Employing non-encapsulated (14) C-UBT, 74 out of 100 dyspeptic patients were found to be H. pylori positive. Discordant (14) C-UBT results were obtained in 4/74 (5.4%) cases using these two protocols. By employing encapsulated and nonencapsulated (14) C UBT protocols, sensitivities of (14) C-UBT were found to be 90.5 versus 98.6% at 10 and 91.8 versus 97.2% at 15 minutes respectively; while these were 94.6 versus 100, 90.7 versus 98.6 and 83.7 versus 93.2% considering any one, two or all three positive values respectively. CONCLUSIONS: Incomplete/non-resolution of (14) C urea capsule in stomach during the phase of breath collections appears to decrease sensitivity of encapsulated (14) C-UBT as compared to nonencapsulated protocol for detection of H. pylori infection. PMID- 24237715 TI - Ultrastructural morphogenesis of an amphibian iridovirus isolated from Chinese giant salamander (Andrias davidianus). AB - Haemorrhagic disease of Chinese giant salamanders (Andrias davidianus) (CGSs) is an emerging condition caused by an iridovirus of the genus Ranavirus within the family Iridoviridae. Several studies have described different biological properties of the virus, but some aspects of its replication cycle, including ultrastructural alterations, remain unknown. The aim of the present study was to describe the morphogenesis of Chinese giant salamander iridovirus (GSIV) in an epithelioma papulosum cyprinid (EPC) cell line at the ultrastructural level. Cells were infected with GSIV at a multiplicity of infection (MOI) of 10 and examined at 1, 2, 4, 6, 12, 24, 48, 72, 84 and 96 h post infection. GSIV entered EPC cells by endocytosis or fusion after adsorption to the cell membrane. Following uncoating, the viral cores translocated to the nucleus and the virus began to replicate. Different stages of virus self-assembly were observed in the slightly electron-lucent viromatrix near the cell nucleus. In the late phase of virus infection, most nucleocapsids were mature and formed a typical icosahedral shape and aggregated in pseudocrystalline array at the viromatrix or were budding at the plasma membrane. Virus infection was readily detected by electron microscopy before cytopathic effect appeared in cell culture. The EPC cell line represents a suitable in-vitro model for study of GSIV morphogenesis and characterization of the GSIV replication cycle. PMID- 24237716 TI - The integrated evaluation of the results of oncoplastic surgery for locally advanced breast cancer. AB - The optimal surgical management of locally advanced breast cancer (LABC) remains undefined. The aim of the study was to obtain long-term results of oncoplastic surgery in terms of overall survival, loco-regional recurrence, and quality of life in case of LABC. Prospective cohort study enrolled 60 patients with stage III breast cancer. Forty-two (70%) patients received neo-adjuvant chemotherapy, 28 patients were considered suitable for surgery as initial treatment option. Type II oncoplastic surgery was performed for all patients: hemimastectomy and breast reconstruction with latissimus dorsi flap - for 29 (48.3%), lumpectomy - 31 (51.7%), and reconstruction with subaxillary flap for four (6.7%), with bilateral reduction mammoplasty - 14 (23.3%) and with J-plastic - 13 (21.7%) patients. Adjuvant chemotherapy and hormonal therapy followed surgery for all, except one, patients. Sequential radiotherapy was administered for all patients. The mean period of follow-up was 86 months. Postoperative morbidity rate was 5%. Local-regional recurrence was detected in six (10%) patients. After reoperation no local relapse was diagnosed. However, three of these patients had systemic dissemination of the disease. Distant metastasis was detected in 23 (38.3%) patients. Distant metastasis-free survival at 5 years was 61.7%. Fourteen patients died (23.3%). A total of 87.2% of the patients had good and excellent esthetic outcome. Oncoplastic breast-conserving surgery can be proposed for selected patients with LABC with acceptable complication, local recurrence rate, and good esthetic results. PMID- 24237717 TI - Is muscle strength ratio a criterion for diagnosis of site-specific muscle loss? AB - AIM: Recently, data have questioned the homogenous model of sarcopenia, and suggest that the loss of muscle mass could occur in a site-specific manner. It is unclear, however, whether a muscle strength ratio can be used to assess age related, site-specific muscle loss. The purpose of the present study was to investigate the relationship between the age-related loss of thigh muscle, muscle function and gait performance. METHODS: A total of 55 men aged 18-79 years had muscle thickness (MTH) measured by ultrasound at three sites on the anterior (30% and 50% of thigh length) and posterior (70% of thigh length) aspects of the thigh. MTH ratios were calculated to assess the site-specific muscle loss (anterior 30% : posterior 70% MTH [A30:P70] and anterior 50% :posterior 70% MTH [A50:P70]). Walking performance, maximum isometric knee extension/flexion, toe grasping and handgrip strength were measured. RESULTS: Age was inversely correlated with the ratios of A30:P70 (r=-0.332) and A50:P70 (r=-0.466). There were no significant correlations between the A30:P70 and A50:P70 ratios, and height and bodyweight. The A30 : P70 and A50 : P70 ratios were also not correlated with maximal walking speed. However, the A50:P70 ratio was significantly correlated with zig-zag walking (r=-0.350) and handgrip strength (r=0.334). In addition, these MTH ratios were also correlated with knee extension (r=0.309 and r=0.405), flexion (r=0.306 and r=0.412) and toe-grasping strength (r=0.265 and r=0.336). After adjusting for physical activity, the MTH ratios were still not correlated with ratio of muscle strength. CONCLUSION: Strength ratios did not correlate with MTH ratios. Our cross-sectional analysis suggests that age related site-specific muscle loss could assess the decrease in absolute muscular strength, but not the ratio of muscle strength. PMID- 24237718 TI - Effectiveness of a parental training programme in enhancing the parent-child relationship and reducing harsh parenting practices and parental stress in preparing children for their transition to primary school: a randomised controlled trial. AB - BACKGROUND: Entering primary school is an important childhood milestone, marking the beginning of a child's formal education. Yet the change creates a time of vulnerability for the child, the parents and the parent-child relationship. Failure to adjust to the transition may place the family in a psychologically devastating position. The aims of this study were to test the effectiveness of a parental training programme in enhancing the parent-child relationship and decreasing parental stress by reducing harsh parenting in preparing children for the transition to primary school. METHODS: A randomised controlled trial incorporating a two-group pre-test and repeated post-test was conducted in one of the largest public housing estates in Hong Kong. A total of 142 parents were recruited, with 72 parents randomly assigned to the experimental group and 70 to the control group. Harsh parenting practices, parent-child relationships and parental stress were assessed. RESULTS: In comparison to parents in the control group, those in the experimental group engaged in less harsh parenting practices and reported better parent-child relationships. However, parental stress scores did not differ significantly between the two groups. CONCLUSION: This study addressed a gap in the literature by examining the effectiveness of the training programme for enhancing parent-child relationship and decreasing parental stress at the time of a child's transition to primary school. The findings from this study provide empirical evidence of the effectiveness of the parental training programme and highlight the significance of parenting in promoting a smooth transition for children from kindergarten to primary 1. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01845948. PMID- 24237719 TI - Ordered mesoporous silica prepared by quiescent interfacial growth method - effects of reaction chemistry. AB - Acidic interfacial growth can provide a number of industrially important mesoporous silica morphologies including fibers, spheres, and other rich shapes. Studying the reaction chemistry under quiescent (no mixing) conditions is important for understanding and for the production of the desired shapes. The focus of this work is to understand the effect of a number of previously untested conditions: acid type (HCl, HNO3, and H2SO4), acid content, silica precursor type (TBOS and TEOS), and surfactant type (CTAB, Tween 20, and Tween 80) on the shape and structure of products formed under quiescent two-phase interfacial configuration. Results show that the quiescent growth is typically slow due to the absence of mixing. The whole process of product formation and pore structuring becomes limited by the slow interfacial diffusion of silica source. TBOS-CTAB-HCl was the typical combination to produce fibers with high order in the interfacial region. The use of other acids (HNO3 and H2SO4), a less hydrophobic silica source (TEOS), and/or a neutral surfactant (Tweens) facilitate diffusion and homogenous supply of silica source into the bulk phase and give spheres and gyroids with low mesoporous order. The results suggest two distinct regions for silica growth (interfacial region and bulk region) in which the rate of solvent evaporation and local concentration affect the speed and dimension of growth. A combined mechanism for the interfacial bulk growth of mesoporous silica under quiescent conditions is proposed. PMID- 24237720 TI - Causes and outcomes of asymptomatic gross haematuria in children. AB - AIM: Although asymptomatic gross haematuria (GHU) is relatively common in children, its causes and clinical outcomes are not clearly defined. METHODS: Children with asymptomatic GHU were examined and work-up was performed. Patients with recurrent GHU with proteinuria, or significant proteinuria, were considered for renal biopsy. RESULTS: The male : female ratio of all patients was 190:75, and the median age at onset of GHU was 6.4 years. Patients were grouped according to abnormalities on initial evaluation as follows: idiopathic (50%), proteinuria (21%), hypercalciuria (14%), sonographic abnormality (7%), hypocomplementaemia (4%), familial (3%), and bleeding tendency (2%). Of patients with idiopathic GHU, 38% had a single episode, and of these, 34% had persistent microscopic haematuria, which resolved on follow-up. Late onset proteinuria was accompanied in 11% of patients with recurrent GHU. Nutcracker syndrome was diagnosed in one patient with recurrent idiopathic GHU. Of patients with recurrent GHU, 89% had no proteinuria on follow-up, and GHU and microscopic haematuria resolved in 97% and 89%, respectively. CONCLUSIONS: Our work-up protocol was useful for diagnosis and follow-up planning. Asymptomatic GHU in children was most commonly the idiopathic form. Overall, long-term prognosis appears to be benign; however, careful follow up is essential. PMID- 24237721 TI - When genes move farther than offspring: gene flow by male gamete dispersal in the highly philopatric bat species Thyroptera tricolor. AB - For species characterized by philopatry of both sexes, mate selection represents an important behaviour for inbreeding avoidance, yet the implications for gene flow are rarely quantified. Here, we present evidence of male gamete-mediated gene flow resulting from extra-group mating in Spix's disc-winged bat, Thyroptera tricolor, a species which demonstrates all-offspring philopatry. We used microsatellite and capture-recapture data to characterize social group structure and the distribution of mated pairs at two sites in southwestern Costa Rica over four breeding seasons. Relatedness and genetic spatial autocorrelation analyses indicated strong kinship within groups and over short distances (<50 m), resulting from matrilineal group structure and small roosting home ranges (~0.2 ha). Despite high relatedness among-group members, observed inbreeding coefficients were low (FIS = 0.010 and 0.037). Parentage analysis indicated mothers and offspring belonged to the same social group, while fathers belonged to different groups, separated by large distances (~500 m) when compared to roosting home ranges. Simulated random mating indicated mate choice was not based on intermediate levels of relatedness, and mated pairs were less related than adults within social groups on average. Isolation-by-distance (IBD) models of genetic neighbourhood area based on father-offspring distances provided direct estimates of mean gamete dispersal distances (r^) > 10 roosting home range equivalents. Indirect estimates based on genetic distance provided even larger estimates of r^, indicating direct estimates were biased low. These results suggest extra-group mating reduces the incidence of inbreeding in T. tricolor, and male gamete dispersal facilitates gene flow in lieu of natal dispersal of young. PMID- 24237722 TI - Improvement of peripheral nerve defects using a silicone conduit filled with hepatocyte growth factor. AB - OBJECTIVE: To assess local effects of hepatocyte growth factor (HGF) on peripheral nerve repair in a rat sciatic nerve transection model. STUDY DESIGN: Sixty male, healthy, white Wistar rats were randomized into 4 experimental groups: In the sham-operated group, sciatic nerve was exposed and manipulated. In the transected control group, the left sciatic nerve was transected. In the silicone graft group (SIL), a 10-mm defect was made and bridged using a silicone tube. The graft was filled with phosphate-buffered saline in the SIL group and with HGF in the SIL/HGF group. RESULTS: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass measurement, and morphometric indices found earlier regeneration of axons in the SIL/HGF than in the SIL group (P < .05). Immunohistochemical study clearly found more positive location of reactions to S-100 in the SIL/HGF group than in the SIL group. CONCLUSIONS: HGF may have clinical implications for the surgical management of patients after facial nerve transection. PMID- 24237723 TI - SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis): a multidisciplinary approach. AB - OBJECTIVE: The aim of this study is to suggest a model for inquiry and treatment of patients with undiagnosed multiple inflammatory reactions. STUDY DESIGN: A retrospective study was performed using 43 patient records from patients with chronic osteomyelitis of the jaw, treated at the Oral and Maxillofacial Clinic at Sodersjukhuset, Stockholm, Sweden. The diagnoses primary chronic osteomyelitis (PCO) or secondary chronic osteomyelitis (SCO) were eventually made, according to symptoms and course of disease. RESULTS: A total of 85% of the PCO patients fulfilled the criteria of the disorder SAPHO (synovitis-acne-pustulosis hyperostosis-osteitis). The difficulty of settling on the diagnosis, as well as the length and diversity of treatment, was extreme. After treatments became multidisciplinary, time between diagnosis and cure was halved. CONCLUSIONS: In order to improve diagnostics and treatment of patients with chronic inflammatory disease of the jaw, a structured plan for examination and treatment is proposed. PMID- 24237724 TI - Efficacy of aloe vera gel as an adjuvant treatment of oral submucous fibrosis. AB - OBJECTIVE: Definitive therapy is not defined for the management of oral submucous fibrosis (OSMF). This study evaluated the efficacy of aloe vera gel as an adjuvant treatment of OSMF. STUDY DESIGN: A double-blind, placebo-controlled, parallel-group randomized controlled trial was conducted on 60 subjects with OSMF divided into medicinal treatment (submucosal injection of hyaluronidase and dexamethasone, n = 30) and surgical treatment (n = 30) categories. Each category was randomly divided into groups A (with aloe vera, n = 15 per category) and B (without aloe vera, n = 15 per category). Follow-up assessment for various symptoms was performed, and results were analyzed using paired and unpaired Student t tests. RESULTS: The group receiving aloe vera had a significant improvement in most symptoms of OSMF (P < .01) compared with the non-aloe vera group, in both the medicinal and surgical categories. CONCLUSIONS: Aloe vera gel was effective as an adjuvant in treatment of OSMF. PMID- 24237725 TI - Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin alphavbeta3 in pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma. AB - OBJECTIVES: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin alphavbeta3 in pleomorphic adenoma (PA), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the level of expression of OPN and its receptors in normal salivary glands (NSG; n = 20), PA (n = 20), PLGA (n = 16), and ACC (n = 22). RESULTS: OPN expression was increased in PLGA and intermediate-/high-grade ACC compared with PA and NSG (median scores, 6, 5, 4, and 4, respectively). CD44 expression was reduced in PA, PLGA, and ACC. OPN expression levels were moderately correlated with CD44 in PLGA. Integrin alphavbeta3 was not expressed in PA and ACC and was seen in only 1 case of PLGA. CONCLUSIONS: OPN is expressed in salivary gland tumors but does not correlate well with CD44 and alphavbeta3. PMID- 24237726 TI - Oral mucosa optical biopsy by a novel handheld fluorescent confocal microscope specifically developed: technologic improvements and future prospects. AB - OBJECTIVE: This pilot study evaluated the baseline effectiveness of a novel handheld fluorescent confocal microscope (FCM) specifically developed for oral mucosa imaging and compared the results with the literature. STUDY DESIGN: Four different oral sites (covering the mucosa of the lip and of the ventral tongue, the masticatory mucosa of the gingiva, and the specialized mucosa of the dorsal tongue) in 6 healthy nonsmokers were imaged by an FCM made up of a confocal fiberoptic probe ergonomically designed for in vivo oral examination, using light at the wavelength of 457 nm able to excite the fluorophore acriflavine hydrochloride, topically administered. In total, 24 mucosal areas were examined. RESULTS: The FCM was able to distinctly define epithelial cells, bacterial plaque, and inflammatory cells and to image submucosal structures by detecting their intrinsic fluorescence. CONCLUSIONS: When compared with other devices, this FCM allowed the user to image each oral site at higher magnification, thus resulting in a clearer view. PMID- 24237727 TI - Calcifying epithelial odontogenic tumor (CEOT): a clinicopathologic and immunohistochemical study and comparison with dental follicles containing CEOT like areas. AB - OBJECTIVE: To describe the clinicopathologic, immunohistochemical, and scanning electron microscopic features of 19 cases of calcifying epithelial odontogenic tumor (CEOT) in comparison to 4 cases of dental follicles containing CEOT-like areas (DF-CEOT). STUDY DESIGN: A collaborative Latin American retrospective study. RESULTS: CEOT and DF-CEOT showed a slight predilection for females, mostly affecting the posterior mandible. CEOTs were classified as epithelium-rich (8 cases), amyloid-rich (4), and calcification-rich (3), and 4 cases showed similar proportion of the 3 components. DF-CEOTs contained odontogenic epithelium, amyloid, calcification, and clear cells. Epithelial cells were positive for cytokeratins CK5 and CK19, E-cadherin, and syndecan 1 (CD138), and focally for amyloid A. In CEOT, amyloid was positive for CD138 and amyloid A, and calcification for CK5, CD138, and amyloid A. In DF-CEOT, calcification was positive for amyloid A. CEOT showed higher Ki-67 protein and minichromosome maintenance complex component 2 (MCM-2) labeling indices than did DF-CEOT. In scanning electron microscopy, CEOT calcified material resembled bone in the 3 cases classified as calcification-rich. CONCLUSIONS: CEOT and DF-CEOT showed histomorphologic and immunohistochemical similarities, and the histogenetic significance of these features should be further studied. PMID- 24237728 TI - Movement of the patient and the cone beam computed tomography scanner: objectives and possible solutions. AB - OBJECTIVE: This study aimed (1) to determine whether scanner arm rotation causes significant movement of the head restraint and (2) to measure patient movement and its variation during the scan. STUDY DESIGN: The iCAT scanner and a high speed camera were used. The 40 patients were divided into 2 groups: the open-eyed group and the blindfolded group. RESULTS: The mean level of head restraint movement was 0.130 mm, with a significantly higher level at the beginning, probably owing to the accelerating arm. Mean movement of patients was 1.135 mm and 1.119 mm in the open-eyed and blindfolded groups, respectively. Patient movement was also significantly higher at the beginning of the scan, when noise and vibrations are likely to surprise the patient. CONCLUSIONS: Patient instruction and a dry-run scan should be done by clinicians. Manufacturers should consider separating the seat and head restraint from the rest of the scanner to avoid vibration transfer. PMID- 24237729 TI - Evaluation of image quality parameters of representative intraoral digital radiographic systems. AB - OBJECTIVE: The aim of this study was to compare imaging properties of 20 intraoral digital systems objectively. STUDY DESIGN: Using a direct current x-ray source and a radiographic phantom, a series of radiographs was made from the lowest exposure time until the sensor saturated. Images were captured and stored. Incident exposures were measured using a radiation meter. Gray scale, spatial resolution, and contrast/detail detectability were evaluated. Presence of 7 distinct steps spanning the gray levels from 0 to 255 was used to define the exposure latitude. An "optimal" exposure, the lowest exposure where maximum spatial resolution and contrast/detail detectability were achieved, was determined. RESULTS: The systems varied greatly in latitude, "optimal" exposure, and image quality. This may not be readily apparent to the naked eye or when clinical images are compared. CONCLUSIONS: Objective assessment of image quality with a quality assurance tool makes it possible to evaluate and compare the various intraoral digital systems. PMID- 24237730 TI - Angina presenting as orofacial pain: a case report. PMID- 24237731 TI - Characterization and management of exfoliative cheilitis: a single-center experience. AB - Exfoliative cheilitis (EC) is a rare inflammatory condition affecting the vermilion of the lips and characterized by production of a thick keratin scale. Given the limited available data, the approach to optimal management of EC remains unclear. The objective of this retrospective study was to characterize the clinical features, management, and outcomes of a series of patients with EC. Fifteen patients with a median age of 59 years and a female-to-male ratio of 2:1 were diagnosed with EC from 2000 to 2010. Parafunctional lip licking (53%) and a history of psychiatric disorders (40%) were common. Ten patients (66%) returned for follow-up, with an overall response rate (partial or complete) of 80% at a median of 2 months, most frequently associated with the use of topical calcineurin inhibitors or moisturizing agents. Management of EC with topical calcineurin inhibitors and moisturizing agents is associated with clinical improvement, but prospective trials are needed. PMID- 24237732 TI - Evaluation of the literature: evidence assessment tools for clinicians. AB - The progressive improvement in the quality of scientific articles has led to an increase in difficulty in reading and interpreting them so that now clinical knowledge and experience must be complemented by methodological, statistical and computer skills. The aim of this article is to offer practitioners the tools, the simplest keys, that will allow them to understand and critically judge the results of scientific studies. The "peer-review" process of a clinical article submitted to a journal is described and the Science Citation Index and the Impact Factor are presented to the reader as essential instruments to evaluate a specific article's impact and the impact of a given journal on the scientific world, respectively. An article should be evaluated on the basis of some key issues which include, at least, an assessment of methodological aspects, a critical analysis of the statistical component and a proper understanding of the clinical impact of the study outcomes. The standard approach for evaluating the quality of individual studies is based on a hierarchical grading system of research design which represents an essential tool to identify the strength of the evidence of an article. Many different biases may affect the reliability of study results. Randomized Control Trials (RCTs) and Systematic Reviews (SRs) are able to minimize the number of biases and thus are at the highest level of the scale of evidence representing the final steps of a treatment's "career." Finally, moving from research to clinical practice, attention on the clinical impact of study's outcomes is of paramount importance as the literature contains studies (including RCTs) that present statistically significant results but which, from the clinical standpoint, are only relatively or not at all significant. Clinical Practice Guidelines represent a useful tool for practitioners assisting the decision-making process when choosing the most appropriate treatment for their patients. PMID- 24237733 TI - Evidence supports the impact of smoking cessation protocols in periodontal therapy. PMID- 24237734 TI - An evaluation of a systematic review for dysphagia in head/neck cancer. PMID- 24237735 TI - Low-fluoride toothpastes may not lead to dental fluorosis but may not control caries development. Standard fluoride toothpastes can control caries development but may lead to dental fluorosis. PMID- 24237736 TI - Clinical oral examinations may not be predictive of dysplasia or oral squamous cell carcinoma. PMID- 24237737 TI - Pregnancy is associated with various degrees of increased gingival inflammation in healthy women. PMID- 24237738 TI - Coronally advanced flaps (CAF) plus connective tissue graft (CTG) is the gold standard for treatment of Miller class I and II gingival defects. PMID- 24237739 TI - Behavioral interventions may reduce dental anxiety and increase acceptance of dental treatment in dentally fearful adults. PMID- 24237740 TI - Dentists who participate in a practice-based research network may adopt less invasive approaches to treating dental caries. PMID- 24237741 TI - Replacement of dental restorations in patients with subjective health impairment has limited effect on self-reported changes of health. PMID- 24237742 TI - The re-establishment of a papilla may be difficult when there is no tooth involved in the implant-borne fixed restorations of the anterior maxilla. PMID- 24237743 TI - 10- and 20-percent benzocaine gels are effective for the temporary relief of toothache and are well-tolerated. PMID- 24237744 TI - Visual screening for oral cancer may reduce oral cancer mortality in high-risk adult populations through early diagnosis and treatment. PMID- 24237745 TI - The efficacy of fluoride on root caries progression may be dose-dependent. PMID- 24237746 TI - Smoking is an independent risk factor for the development of oral candidiasis (OC) in HIV-1 infected persons. PMID- 24237747 TI - Patients with both oral leukoplakia and oral submucous fibrosis had a higher rate of malignant transformation compared to patients with oral leukoplakia or oral submucous fibrosis alone. PMID- 24237748 TI - Middle-aged (45 to 64 years) persons may have different factors associated with root caries than older adults (>= 65). PMID- 24237749 TI - Predictors of hyperlactataemia among children presenting with malaria in a low transmission area in The Gambia. AB - BACKGROUND: Hyperlactataemia and metabolic acidosis are important risk factors for malaria death, but measuring lactate at the point of care is not financially viable in many resource-poor settings. This study aimed to identify combinations of routinely available parameters that could identify children at high risk of hyperlactataemia. METHODS: Using data from a study of Gambian children aged six months to 16 years with severe or uncomplicated malaria, logistic regression modelling with a forward stepwise model selection process was used to develop a predictive model for hyperlactataemia from routinely available demographic, clinical and laboratory parameters. Potential predictors of hyperlactataemia considered for the modelling process were patient characteristics (age, sex, prior use of anti-malarials, and weight percentile for age), respiratory symptoms (deep breathing, irregular respiration, use of accessory muscles of respiration, lung crepitations, grunting respiration, cough, and age-specific respiratory rate), other clinical parameters recorded at presentation (duration of symptoms, Blantyre coma score, number of convulsions prior to admission, axillary temperature, dehydration, severe prostration, splenomegaly) and laboratory measures from blood tests (percentage parasitaemia, white cell count, lymphocyte count, neutrophil count, monocyte count, platelet count, haemoglobin level, blood glucose level). RESULTS: 495 children were included, and 68 (14%) had laboratory confirmed hyperlactataemia (lactate > 7 mmol/L). Four features were independently associated with increased hyperlactataemia risk in a multivariable age- and sex adjusted model: lower Blantyre score (odds ratio (OR) compared to score 5 = 2.68 (95% CI, 1.03-6.96) for score 3-4 and 6.18 (95% CI, 2.24-17.07) for score 0-2, p = 0.001), higher percentage parasitaemia (OR = 1.07 (1.03-1.11) per 0031% increase, p < 0.001), high respiratory rate for age (OR = 3.09 (1.50-6.38) per unit increase, p = 0.002), and deep breathing (OR = 2.81 (1.20-6.60), p = 0.02). Cross-validated predictions from the final model achieved area under the receiver operating characteristic curve of 0.83. CONCLUSIONS: This study identified predictors of hyperlactataemia requiring only simple bedside clinical examination and blood film examination that can be carried out in resource-limited settings to quickly identify children at risk of dangerously raised lactate. A simple spreadsheet tool implementing the final model is supplied as supplementary material. PMID- 24237750 TI - The automation of routine light transmission platelet aggregation. AB - INTRODUCTION: The investigation of platelet function by aggregometry requires specialist equipment and is labour intensive. We have developed an automated platelet aggregation method on a routine coagulation analyser. METHODS: We used a CS-2000i (Sysmex) with prototype software to perform aggregation in platelet-rich plasma (PRP), using the following agonists: ADP (0.5-10 MUm), epinephrine (0.5-10 MUm), collagen (0.5-10 mg/MUL), ristocetin (0.75-1.25 mg/mL) and arachidonic acid (0.12-1.0 mm). Platelet agonists were from Hyphen Biomed, and an AggRAM aggregometer (Helena Biosciences) was used as the reference instrument. RESULTS: CS-2000i reaction cuvette stirrer speed was found to influence reaction sensitivity and was optimized to 800 rpm. There were no clinically significant changes in aggregation response when the PRP platelet count was 150-480 x 10(9) /L, but below this there were changes in the maximum amplitude (MA) and slope (rate). Dose response with each of the agonists was comparable between CS-2000i and an AggRAM aggregometer and normal subjects receiving antiplatelet drugs. Aggregation imprecision was similar on both the CS-2000i and AggRAM systems, with a cv for 2-5 MUm ADP MA and slope varying between 3-12%. CONCLUSION: Our preliminary studies indicated that optimal sensitivity using the CS-2000i was obtained with a reaction cuvette stirrer speed of 800 rpm and a PRP platelet count of 200-300 x 10(9) /L; aggregation with a PRP count <100 x 10(9) /L showed poor sensitivity. Imprecision and detection of antiplatelet drug effects was similar between the CS-2000i and AggRAM. These data demonstrate that CS-2000i is comparable to a stand-alone aggregometer, although CS-2000i has the advantages of walk-away technology and also required a smaller sample volume than the AggRAM (44% less). PMID- 24237751 TI - Is topical zinc effective in the treatment of melasma? A double-blind randomized comparative study. AB - BACKGROUND AND OBJECTIVES: Zinc plays a role in skin health, and preliminary data have shown its beneficial effects for melasma. We compared the effect of topical zinc with that of hydroquinone as the standard treatment on severity of melasma. PATIENTS AND METHODS: Ninety-three women with melasma were randomized to receive zinc sulfate 10% or hydroquinone 4% solutions once daily for 2 months. They were followed for an additional 3 months while using sunscreen. The severity of melasma was assessed at baseline and at 2 and 5 months using the Melasma Area and Severity Index (MASI). RESULTS: Eighty-two patients completed the study. The MASI score fell significantly in both groups, but a greater decrease was seen in those who received hydroquinone (43.5 +/- 15.5% vs 18.6 +/- 20.8%, p < .001). Postinflammatory pigmentation occurred in 5.2% of the zinc group and irritation in 30.9% of the hydroquinone group. CONCLUSION: Topical zinc therapy is not highly effective in reducing the severity of melasma, but further trials are needed to determine whether adding zinc to current topical treatments could improve treatment response. PMID- 24237752 TI - The effect of individual education on patients' physical activity capacity after myocardial infarction. AB - The present study aims to determine the effects of individual education and counselling given to first-time myocardial infarction patients, including its effect on compliance with treatment. The sample comprised 90 patients, 45 in the intervention and 45 in the control group, selected by sequential sampling from first-time myocardial infarction patients. Data were collected between April and November 2008 by means of patient information form, International Physical Activity Questionnaire, 6 min walk test, Modified Borg Scale, Morisky Medication Adherence Scale and Canadian Cardiovascular Society Angina Grade Classification. In the intervention group more improvement was observed in comparison with the control group in terms of frequency of physical activity, body mass index and waist circumference. It was observed that the intervention group's metabolic equivalent of task values and 6 min walk test distance increased more in comparison with the control group 3 months after baseline, and there was a statistically significant difference. The results indicated that individual education and counselling provided to patients having experienced acute myocardial infarction increased functional capacity by providing patients with advice on how to lose weight and by improving compliance with treatment through physical activity behaviours (frequency and duration). PMID- 24237754 TI - Management of the endoplasmic reticulum stress by activation of the heat shock response in yeast. AB - In yeast Saccharomyces cerevisiae, accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR), which is mediated by Hac1p. The heat shock response (HSR) mediated by Hsf1p, mainly regulates cytosolic processes and protects the cell from stresses. Here, we find that a constitutive activation of the HSR could increase ER stress resistance in both wild-type and UPR-deficient cells. Activation of HSR decreased UPR activation in the WT (as shown by the decreased HAC1 mRNA splicing). We analyzed the genome-wide transcriptional response in order to propose regulatory mechanisms that govern the interplay between UPR and HSR and followed up for the hypotheses by experiments in vivo and in vitro. Interestingly, we found that the regulation of ER stress response via HSR is (1) only partially dependent on over-expression of Kar2p (ER resident chaperone induced by ER stress); (2) does not involve the increase in protein turnover via the proteasome activity; (3) is related to the oxidative stress response. From the transcription data, we also propose that HSR enhances ER stress resistance mainly through facilitation of protein folding and secretion. We also find that HSR coordinates multiple stress-response pathways, including the repression of the overall transcription and translation. PMID- 24237755 TI - Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer. AB - BACKGROUND: The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) ( Drugs 72(Suppl 1):28-36, 012.), p53 ( Med Sci Monit 11(6):HY11-HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) ( J Thorac Oncol 8(5):582-586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non invasive surrogate for tumor biology with the maximal standardized uptake values (SUVmax) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG-PET SUVmax in NSCLC. METHODS: FDG-PET SUVmax was calculated in chemotherapy naive patients with NSCLC (n=62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUVmax difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUVmax and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUVmax in suggesting chemotherapy resistant tumor markers. RESULTS: The significant tumor type (P=0.045), differentiation (P=0.021), p53 (P=0.000) or ERCC1 (P=0.033) positivity dependent differences of SUVmax values were observed. The tumor differentiation is significantly correlated with SUVmax (R=-0.327), tumor size (R=-0.286), grading (R=-0.499), gender (R=0.286) as well as the expression levels for p53 (R= -0.605) and ERCC1 (R=-0.644). The expression level of p53 is significantly correlated with SUVmax (R=0.508) and grading (R=0.321). Furthermore, multiple stepwise regression analysis revealed that p53 expression was the primary predictor for SUVmax. When the cut-off value of SUVmax was set at 5.15 in the ROC curve analysis, the sensitivity and specificity of SUVmax in suggesting p53 positive NSCLC were 79.5% and 47.8%, respectively. CONCLUSION: The current study suggests that SUVmax of primary tumor on FDG-PET might be a simple and good non-invasive method for predicting p53-related chemotherapy resistance in NSCLC when we set the cu-off value of SUVmax at 5.15. PMID- 24237757 TI - Metabolic cost of locomotion during treadmill walking with blood flow restriction. AB - We explored whether interval walking with blood flow restriction (BFR) increases net metabolic cost of locomotion in healthy young men at their optimal walking speed. We also determined whether decreased walking economy resulting from BFR might be accompanied by an increase in ventilation relative to VO2 and VCO2 . Finally, we examined possible relationships between the changes in ratings of perceived exertion (RPE) and those obtained in minute ventilation (VE ) during walking with BFR. Eighteen healthy men (age: 22.5 +/- 3.4 years) performed graded treadmill exercise to assess VO2max . In a randomized fashion, participants also performed five bouts of 3-min treadmill exercise with and without BFR at their optimal walking speed. Walking with BFR elicited an overall increase in net VO2 (10.4%) compared with that seen in the non-BFR condition (P<0.05). The participants also demonstrated greater VE and VE /VO2 values while walking with BFR (P<0.05). Conversely, VE /VCO2 was similar between conditions at each walking bout. We found no significant correlation between the changes in VE and RPE induced by walking with BFR (r = 0.38, P>0.05). Our results indicate that (i) BFR decreases net walking economy in healthy young men, even at their optimal walking speed; (ii) heightened ventilatory drive may explain a small proportion of BFR effects on walking economy; and (iii) the ventilatory responses to BFR walking may be largely independent of changes in perceived exertion and are likely matched to the flux of CO2 between muscles and respiratory centres. PMID- 24237756 TI - A study based on records taken at time of hoof trimming reveals a strong association between the IQ motif-containing GTPase-activating protein 1 (IQGAP1) gene and sole hemorrhage in Holstein cattle. AB - Feet and leg problems have a major effect on the well-being and lifespan of the dairy cow and thus are economically important to the dairy farmer. Apart from approaches using genetic selection for classical traits from conformation scoring, attempts for genetic improvement can be based either on records of individual disease cases or on records of disorder status at time of hoof trimming. In this study, 1,962 first-lactation cows were subjected to hoof trimming with an assessment of disorder status for sole hemorrhage as a binary trait. Cows were from 7 large commercial herds in Mecklenburg-Western Pomerania (northeastern Germany) that had similar housing with cubicles, slatted flooring, little use of straw for bedding, and total mixed ration feeding. Cows were trimmed and assessed once, focusing on cows in the first half of the lactation. Herds were visited at intervals to enable recording of cohorts at a similar stage of lactation. Each cohort or herd-visit included between 31 and 165 cows. Additional measurements included body weight, back fat thickness, and body condition at time of trimming. Further data on dairy production, conformation scores, and reproductive performance were merged after collection of records had finished. The DNA extracted from blood of 1,183 cows was used for analysis with a custom-made array of 384 single nucleotide polymorphisms (SNP). The SNP were selected according to results from the literature for effects in classical conformation traits, from biochemical pathway analysis, and from comparative analysis of putative candidate genes in cattle, pigs, and sheep. Selection of cohorts of cows for SNP chip analysis was such that cohorts with extreme frequencies of disorders and cohorts with slightly deviating housing systems were excluded in this first step. The results from a mixed threshold model analysis with genotype included as a fixed effect and accounting for relationships among animals revealed that the intronic SNP rs29017173 (A/G) within the IQ motif containing GTPase-activating protein 1 (IQGAP1, Bos taurus autosome 21) was significantly associated with disorder status. Back-transformed means of disorder status for the 3 genotypes were 0.37 (AA), 0.52 (AG), and 0.56 (GG). Using the full data set of 1,962 cows, including the less-suitable cohorts, gave back transformed means of 0.51 (AA), 0.58 (AG), and 0.62 (GG). As SNP rs29017173 is included on the Illumina BovineSNP50 DNA Analysis BeadChip (Illumina Inc., San Diego, CA), a sample of 2,394 artificial insemination sires from the German calibration sample for genomic selection from birth years 1998 to 2003 was studied for possible correlated effects. The A/G polymorphism of SNP rs29017173 studied here was also associated with substantial effects for feet and leg traits from the classical conformation score system. Selection using this polymorphism will be facilitated by the fact that the same allele is favored for all traits with substantial effects. PMID- 24237758 TI - Impact of structural heart disease on the acute complication rate in atrial fibrillation ablation: results from the German Ablation Registry. AB - INTRODUCTION: Catheter ablation (CA) has emerged as a widespread therapeutic option in the treatment of atrial fibrillation (AF). Currently, no safety data with regard to the impact of the underlying structural heart diseases (SHD) are available. We sought to assess the risk for acute and long-term complications during CA of AF in relation to underlying SHD. METHODS AND RESULTS: We included 6,211 patients in a prospective registry undergoing CA of AF in 41 nationwide centers. All patients were divided into 4 groups according to the underlying heart disease: No SHD (69.4%), hypertensive heart disease (HHD) (12.0%), coronary artery disease (CAD) (15.1%), and cardiomyopathy (CM) (3.6%). In univariate analysis, patients with HHD had an overall complication rate of 7.28%, whereas patients without an SHD had a significantly lower rate of 6.01% (P < 0.01). Multivariate analysis revealed that HHD (adjusted odds ratio [OR]: 1.97 [95% confidence interval (CI): 1.02-3.83], P = 0.0442) and age (years; OR: 1.04 [95% CI: 1.01-1.07], P = 0.0155) were independent predictors of severe, nonfatal complications and death. Other SHD including CAD (OR: 1.48 (0.73-3.00), P = 0.2797) and CM (OR: 2.37 [0.70-7.99], P = 0.1630) failed to reach statistical significance. Male sex was protective (OR: 0.47 [95% CI: 0.27-0.81], P = 0.0062). CONCLUSION: In general, CA of AF has a low number of severe complications. In our prospective registry HHD emerged as an independent predictor of severe, nonfatal complications during AF ablation but other SHD including CAD and CM did not. The influence of HHD on the complication rate should be considered in patient selection. PMID- 24237759 TI - Mini-Mental State Examination subscores indicate visuomotor deficits in Alzheimer's disease patients: A cross-sectional study in a Dutch population. AB - AIM: In diagnostics of Alzheimer's disease (AD), the Mini-Mental State Examination (MMSE) questionnaire is frequently used to test cognitive decline. The final subtest of the MMSE, in which patients have to copy two interlocking pentagons, tests a variety of visuomotor functions. Recent imaging studies suggest that visuomotor function could decline in early stage AD, as a result of degeneration of the brain networks involved. The goal of the present study was to compare memory and visuomotor function in AD patients, reflected by the MMSE subscores for orientation, recall and interlocking pentagons. METHODS: The MMSE subscores for orientation, recall and interlocking pentagons of 125 AD patients was extracted from their medical history. Patients were divided into three groups based on disease duration. Using related-samples Wilcoxon signed-rank tests, the performance between subtests using normalized subscores was compared within each group. RESULTS: In all three groups, the subscores of recall and interlocking pentagons were significantly lower than orientation. No differences were found between the subscores of recall and interlocking pentagons. CONCLUSIONS: The presented data suggest that memory function and visuomotor function are equally impaired in the present study population. This could indicate that visuomotor dysfunction might be a more important clinical feature of AD than is currently assumed. This knowledge can be used to develop new tests and markers for AD reflecting deficits in visuomotor functions, such as quantification of eye and hand movements. PMID- 24237760 TI - Identification accuracy and diversity reproducibility associated with internal transcribed spacer-based fungal taxonomic library preparation. AB - This study investigated analytical parameters that are inherently relevant to identifying and quantifying fungal communities based on polymerase chain reaction amplicons. Specifically, we evaluated the accuracy of the BLASTn-based identification for internal transcribed spacer (ITS) sequences generated from pure cultures, and quantified the reproducibility of relative abundances as well as alpha and beta diversity measurements using duplicated environmental samples. The BLASTn-based method produced accurate fungal identification for the pure culture sequences at the genus rank. Percentages of the sequences assigned to correct genera were 99.8%, 99.8% and 99.9% for Alternaria alternata, Cladosporium cladosporioides and Epicoccum nigrum respectively. These fractions were smaller for Aspergillus fumigatus and Penicillium chrysogenum, which have dual nomenclatures or sibling species that are indistinguishable by ITS sequences. Our duplicate environmental analyses demonstrated that alpha diversity and relative abundance levels were reproducible (r(2) > 0.9), that variability decreases with increased sequence quantity, and that the differences in distinct environmental samples were larger than differences in replicate samples (beta diversity). These results serve to better characterize the identification and quantification limits of ITS-based fungal taxonomic studies, and demonstrate that while diversity quantification is reproducible, limitations in ITS-based taxonomic identification and dual nomenclature conventions are current barriers to identification accuracy. PMID- 24237761 TI - Why mosaic? Gene expression profiling of African cassava mosaic virus-infected cassava reveals the effect of chlorophyll degradation on symptom development. AB - Cassava mosaic disease, caused by cassava begomoviruses, is the most serious disease for cassava in Africa. However, the pathogenesis of this disease is poorly understood. We employed high throughput digital gene expression profiling based on the Illumina Solexa sequencing technology to investigate the global transcriptional response of cassava to African cassava mosaic virus infection. We found that 3,210 genes were differentially expressed in virus-infected cassava leaves. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that genes implicated in photosynthesis were most affected, consistent with the chlorotic symptoms observed in infected leaves. The upregulation of chlorophyll degradation genes, including the genes encoding chlorophyllase, pheophytinase, and pheophorbide a oxygenase, and downregulation of genes encoding the major apoproteins in light-harvesting complex II were confirmed by qRT-PCR. These findings, together with the reduction of chlorophyll b content and fewer grana stacks in the infected leaf cells, reveal that the degradation of chlorophyll plays an important role in African cassava mosaic virus symptom development. This study will provide a road map for future investigations into viral pathogenesis. PMID- 24237762 TI - PFAPA syndrome: clinical characteristics and treatment outcomes in a large single centre cohort. AB - OBJECTIVES: This paper aims to describe clinical and laboratory features and disease outcome in a single-centre cohort of patients with PFAPA syndrome (Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis) and to test performance of diagnostic and therapeutic algorithms. METHODS: Patients fulfilling criteria were selected from the fever clinic population. Prospective follow-up together with recruitment of newly diagnosed patients followed pre defined guidelines. Diagnostic and therapeutic algorithms and definitions of outcome and therapy response were formulated. Paired blood samples during febrile and afebrile periods were compared. RESULTS: Out of 176 patients referred for suspected periodic fever 125 children fulfilled criteria. Their age at onset was 23 months, median episode duration 3.5 days at 4-week intervals. Fever was associated with pharyngitis (91%), cervical adenitis (78%) and aphtae (41%). Among therapeutic options, episodic prednisone proved to be the most common first line treatment. Administered to 77 patients, it reduced symptoms in 94%. Tonsillectomy led to the full symptom resolution in all 18 patients. Forty-six patients reached disease remission. CONCLUSIONS: Distribution of typical symptoms, response to therapies and disease outcome in a large patient cohort were documented. We offer diagnostic and therapeutic algorithms that have proven effective during this prospective trial. Our findings support the general belief of benign nature of this aetiologically unclear condition, despite proportion of patients having persistent disease for years. Maintenance of normal findings in afebrile intervals, striking response to a single dose of prednisone and normal growth and development together with spontaneous tendency towards prolongation of afebrile intervals are important confirmatory features of PFAPA syndrome. PMID- 24237763 TI - Expression of calgranulin A/B heterodimer after acute inhalation of endotoxin: proteomic approach and validation. AB - BACKGROUND: The acute inhalation of endotoxin mimicks several aspects of the inflammation related to chronic obstructive pulmonary disease (COPD). The aim of the current study was to identify and to validate biomarkers of endotoxin-induced airways' inflammation. METHODS: The cellular count in the induced-sputum, was measured before and after an inhalation of 20 mcg endotoxin, in 8 healthy volunteers. A proteomic analysis was applied to identify the more relevant proteins expression, before measurement by ELISA. The amplitude and the repeatability of the markers were evaluated among another population of 12 healthy subjects. RESULTS: There was a significant rise of viable cells (p <0.01), macrophages (p <0.05), and neutrophils (p <0.02) 24 hours after endotoxin inhalation, and of neutrophils (p <0.02) and lymphocytes (p <0.05) at 6 hours. Among the highest amplitude responses, the two dimensional electrophoretic separation shown proteolytic activity and overexpression of protein spots. By MALDI-TOF mass spectrometry, the last were identified as calgranulin A and B. The expression of the bioactive A/B heterodimeric complex was confirmed by ELISA both in the sputum (p <0.01) and at the blood level (p <0.01). The intra-subject repeatability of the sputum calgranulin A/B was highly significant (p <0.0001). CONCLUSION: In healthy subjects, the inhalation of endotoxin induced expression of sputum calgranulin A/B that could be a biomarker of the endotoxin response/exposure. PMID- 24237765 TI - The dynamical study of O(1D) + HCl(v = 0, j = 0) reaction at hyperthermal collision energies. AB - BACKGROUNDS: The quasi-classical trajectory calculations for O(1D) + HCl -> OH + Cl (R1) and O(1D) + HCl -> ClO + H (R2) reactions have been performed at hyperthermal collision energies (60.0, 90.0, and 120.0 kal/mol) on the 1A' state. Reaction probabilities and integral cross sections are calculated. The product rotational distributions for the two channels, and the product rotational alignment parameters are investigated. Also, the alignment and the orientation of the products have been predicted through the angular distribution functions (concerning the initial/final velocity vector, and the product rotational angular momentum vector). To have a deeper understanding of the natures of the vector correlation between reagent and product relative velocities, a natural generalization of the differential cross section __PDDCS00, is calculated. RESULTS: The OH + Cl channel is the main product channel and is observed to have essentially isotropic rotational distributions. The ClO + H channel is found to be clearly rotationally polarized. CONCLUSIONS: The dynamical, especially the stereodynamical characters are quite different for the two channels of the title reaction. Most reactions occur directly, except for R2 reaction at the collision energies of 60.0 and 120.0 kcal/mol. The alignment and orientation effects are weak/strong for R1/R2 reaction. The well structure on the potential energy surface and hyperthermal collision energies might result in the dynamical effects. PMID- 24237764 TI - Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects. AB - BACKGROUND: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt. METHODS: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. RESULTS: Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. CONCLUSIONS: Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations. PMID- 24237766 TI - Use of vital wheat gluten in aquaculture feeds. AB - SUMMARY: In aquaculture, when alternative protein sources of Fish Meal (FM) in diets are investigated, Plant Proteins (PP) can be used. Among them, Vital Wheat Gluten (VWG) is a proteinaceous material obtained from wheat after starch extraction. "It is mainly composed of two types of proteins, gliadins and glutenins, which confer specific visco-elasticity that's to say ability to form a network providing suitable binding. This will lead to specific technological properties that are notably relevant to extruded feeds". Besides these properties, VWG is a high-protein ingredient with an interesting amino-acid profile. Whereas it is rather low in lysine, it contains more sulfur amino acids than other PP sources and it is high in glutamine, which is known to improve gut health and modulate immunity. VWG is a protein source with one of the highest nitrogen digestibility due to a lack of protease inhibitor activity and to the lenient process used to make the product. By this way, addition of VWG in diet does not adversely affect growth performance in many fish species, even at a high level, and may secure high PP level diets that can induce health damages. PMID- 24237768 TI - Sharps injuries and reporting practices of U.S. dermatologists. AB - BACKGROUND: Sharps injuries pose considerable risk to physicians. We examined prevalence and rates of reporting of sharps injuries of dermatologists and dermatology trainees, focusing on motivations for and barriers to reporting. We identified types of procedures carrying highest risk. OBJECTIVE: To characterize the factors influencing sharps injuries and reporting practices. METHODS AND MATERIALS: Current dermatology residents, fellows, and practicing dermatologists were surveyed using an anonymous electronic survey regarding needlestick injuries. RESULTS: Of 336 dermatologist respondents (26.5% response rate [336/1,268]), 286 (85.1%) reported having had a sharps injury; 116 (40.6%) had occurred within the past year. Sixty-eight injuries occurred during surgery (58.6%), and 106 were perceived to be self-inflicted (91.4%). Physicians most likely to report recent sharps injuries were trainees (26/41, 63.4%), dermatologic surgeons (24/64, 37.5%), and medical dermatologists (3/11, 27.3%). One hundred eighty-three (64%) respondents reported having ever had a sharps injury that went unreported. Dermatologists at academic institutions were more likely to report injuries than those in solo (odds ratio [OR] = 2.97, P = .23) or group (OR=2.29, P < .001) practice. CONCLUSIONS: Sharps injuries are common among dermatologists. Underreporting is common and places providers and patients at risk of blood-borne illnesses. PMID- 24237767 TI - Protein detection through different platforms of immuno-loop-mediated isothermal amplification. AB - Different immunoassay-based methods have been devised to detect protein targets. These methods have some challenges that make them inefficient for assaying ultra low-amounted proteins. ELISA, iPCR, iRCA, and iNASBA are the common immunoassay based methods of protein detection, each of which has specific and common technical challenges making it necessary to introduce a novel method in order to avoid their problems for detection of target proteins. Here we propose a new method nominated as 'immuno-loop-mediated isothermal amplification' or 'iLAMP'. This new method is free from the problems of the previous methods and has significant advantages over them. In this paper we also offer various configurations in order to improve the applicability of this method in real-world sample analyses. Important potential applications of this method are stated as well. PMID- 24237769 TI - Innocuous peripheral nerve stimulation shifts stimulus-response function of painful laser stimulation in man. AB - OBJECTIVES: Electrical peripheral nerve stimulation (PNS) is discussed as an effective neuromodulatory treatment in chronic pain. This human experimental study hypothesized a rightward shift of stimulus-response function as a marker of antinociceptive and analgesic PNS effects. MATERIALS AND METHODS: Innocuous electrical PNS of the left superficial radial nerve trunk evoked paresthesia on the left hand dorsum in 29 healthy volunteers. In this innervation area, laser stimulation was performed before, during, and after PNS. Ten different laser intensities ranging between perception and tolerance thresholds were applied. Cortical laser-evoked potentials (LEP) were recorded, and perceptual ratings were documented. Data were analyzed in low, medium, and high laser intensity categories. Stimulus-response functions were calculated. Laser detection and pain thresholds were interpolated. RESULTS: Interpolated laser thresholds after logarithmic regression were not different from measured thresholds. Laser pain threshold increased during and after PNS. LEP amplitude decreased at medium and high intensities under PNS. Ratings transiently decreased during PNS at medium and high laser intensities. CONCLUSIONS: Modulation of laser pain threshold, perceptual ratings, and LEP indicates a rightward shift of stimulus-response function under PNS. These data emphasize antinociceptive and analgesic effects of PNS in an experimental human model and support its clinical neuromodulative relevance. PMID- 24237770 TI - Fast in vitro methods to determine the speed of action and the stage-specificity of anti-malarials in Plasmodium falciparum. AB - BACKGROUND: Recent whole cell in vitro screening campaigns identified thousands of compounds that are active against asexual blood stages of Plasmodium falciparum at submicromolar concentrations. These hits have been made available to the public, providing many novel chemical starting points for anti-malarial drug discovery programmes. Knowing which of these hits are fast-acting compounds is of great interest. Firstly, a fast action will ensure rapid relief of symptoms for the patient. Secondly, by rapidly reducing the parasitaemia, this could minimize the occurrence of mutations leading to new drug resistance mechanisms.An in vitro assay that provides information about the speed of action of test compounds has been developed by researchers at GlaxoSmithKline (GSK) in Spain. This assay also provides an in vitro measure for the ratio between parasitaemia at the onset of drug treatment and after one intra-erythrocytic cycle (parasite reduction ratio, PRR). Both parameters are needed to determine in vitro killing rates of anti-malarial compounds. A drawback of the killing rate assay is that it takes a month to obtain first results. METHODS: The approach described in the present study is focused only on the speed of action of anti-malarials. This has the advantage that initial results can be achieved within 4-7 working days, which helps to distinguish between fast and slow-acting compounds relatively quickly. It is expected that this new assay can be used as a filter in the early drug discovery phase, which will reduce the number of compounds progressing to secondary, more time-consuming assays like the killing rate assay. RESULTS: The speed of action of a selection of seven anti-malarial compounds was measured with two independent experimental procedures using modifications of the standard [3H]hypoxanthine incorporation assay. Depending on the outcome of both assays, the tested compounds were classified as either fast or non-fast-acting. CONCLUSION: The results obtained for the anti-malarials chloroquine, artesunate, atovaquone, and pyrimethamine are consistent with previous observations, suggesting the methodology is a valid way to rapidly identify fast-acting anti malarial compounds. Another advantage of the approach is its ability to discriminate between static or cidal compound effects. PMID- 24237771 TI - Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model. AB - INTRODUCTION: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. METHODS AND RESULTS: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 MUM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. CONCLUSION: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility. PMID- 24237772 TI - Emergency department bane--dental pain used to obtain narcotics. PMID- 24237773 TI - Segmental alveolar split combined with dental extractions and osteotome sinus floor intrusion in posterior maxilla using BMP-2/ACS allograft for alveolar reconstruction: technical note and report of three cases. AB - The present report is of 3 patients who underwent a new technique for the posterior maxilla. After multiple dental extractions, the segment's alveolar was split to widen it, and the sinus floor was intruded using an osteotome to lengthen the alveolar height and then grafted with a bone morphogenetic protein 2/absorbable allograft without primary wound closure. Implant placement occurred 4 months later, followed by prosthetic restoration. PMID- 24237774 TI - Zygomatic surface marker-assisted surgical navigation: a new computer-assisted navigation method for accurate treatment of delayed zygomatic fractures. AB - PURPOSE: To describe a new method of zygomatic surface marker navigation to treat delayed unilateral zygomatic fractures. PATIENTS AND METHODS: The computed tomography (CT) data for 6 patients were obtained before surgery and imported into the surgical planning software. After 3-dimensional (3D) construction and segmentation, 3D cylindrical-shaped objects in stereolithographic format were placed in position and merged with the data from the fractured segments to mark the area for surface reduction. Data from the unaffected side were used to guide the reduction data for the segments with markers. During surgery, the surface markers were marked by drilling holes in the fractured bones in a process guided by the surgical navigation plan established before osteotomy. The segments were then reduced to the predetermined places using the positions of the hole markers as guides. 3D image comparisons and axial CT measurements were used to evaluate navigation accuracy and bone symmetry. RESULTS: Six patients with unilateral delayed zygomatic fractures were treated using this approach. The mean deviation between the postoperative 3D images and the reduction navigation plan for the 6 patients was +1.24 mm and -1.4 mm. The mean width deviation between the affected and unaffected sides was 1.28 mm, and the mean eminence deviation was 1.22 mm. All patients were followed up for at least 3 months and experienced no obvious complications. CONCLUSIONS: Zygomatic surface marker-assisted surgical navigation can simplify the navigation planning for surgery and avoid the complex protocols needed to create the surgical templates. The navigation accuracy was acceptable, and all 6 patients obtained good facial symmetry. PMID- 24237775 TI - Craniofacial approaches and reconstruction in skull base surgery: techniques for the oral and maxillofacial surgeon. AB - Skull base surgery (SBS) is considered the standard of care in treating benign and malignant lesions of the cranial base. SBS is a multidisciplinary team approach used to treat these complex lesions that may have intracranial extension. SBS can be broken down into 3 steps. Transfacial access is performed, followed by resection with sound oncologic principles, and then reconstruction of the cranial base and facial structures. Functional and esthetic concerns must be addressed by the surgeons. Oral and maxillofacial surgeons frequently perform elective facial osteotomies and treat victims of cranial base trauma. These same principles can be applied to SBS as a part of the skull base team. PMID- 24237776 TI - A paradigm shift in orthognathic surgery? A comparison of navigation, computer aided designed/computer-aided manufactured splints, and "classic" intermaxillary splints to surgical transfer of virtual orthognathic planning. AB - PURPOSE: Advances in computers and imaging have permitted the adoption of 3 dimensional (3D) virtual planning protocols in orthognathic surgery, which may allow a paradigm shift when the virtual planning can be transferred properly. The purpose of this investigation was to compare the versatility and precision of innovative computer-aided designed and computer-aided manufactured (CAD/CAM) surgical splints, intraoperative navigation, and "classic" intermaxillary occlusal splints for surgical transfer of virtual orthognathic planning. MATERIAL AND METHODS: The protocols consisted of maxillofacial imaging, diagnosis, virtual orthognathic planning, and surgical planning transfer using newly designed CAD/CAM splints (approach A), navigation (approach B), and intermaxillary occlusal splints (approach C). In this prospective observational study, all patients underwent bimaxillary osteotomy. Eight patients were treated using approach A, 10 using approach B, and 12 using approach C. These techniques were evaluated by applying 13 hard and 7 soft tissue parameters to compare the virtual orthognathic planning (T0) with the postoperative result (T1) using 3D cephalometry and image fusion (DeltaT1 vs T0). RESULTS: The highest precision (DeltaT1 vs T0) for the maxillary planning transfer was observed with CAD/CAM splints (<0.23 mm; P > .05) followed by surgical "waferless" navigation (<0.61 mm, P < .05) and classic intermaxillary occlusal splints (<1.1 mm; P < .05). Only the innovative CAD/CAM splints kept the condyles in their central position in the temporomandibular joint. However, no technique enables a precise prediction of the mandible and soft tissue. CONCLUSIONS: CAD/CAM splints and surgical navigation provide a reliable, innovative, and precise approach for the transfer of virtual orthognathic planning. These computer-assisted techniques may offer an alternate approach to the use of classic intermaxillary occlusal splints. PMID- 24237777 TI - Comparing cyanoacrylate tissue adhesive and conventional subcuticular skin sutures for maxillofacial incisions--a prospective randomized trial considering closure time, wound morbidity, and cosmetic outcome. AB - PURPOSE: To compare octyl-2-cyanoacrylate (2-OCA) tissue adhesive with subcuticular suture for the closure of incisions in the maxillofacial region to determine 1) whether it is faster than traditional subcuticular suturing, 2) whether the number and length of incisions affect closure time, 3) wound morbidity, 4) patient satisfaction outcome, and 5) cosmetic outcome. MATERIAL AND METHODS: In a prospective randomized clinical trial, 29 patients were allocated to 1 of 2 groups for the closure of skin incisions using 2-OCA or conventional subcuticular skin sutures. Postoperative follow-up evaluated wound healing at 5 to 10 days and at 3 months. Assessment of cosmetic outcome was performed by a plastic surgeon using a modified Hollander Wound Evaluation Scale and a validated visual analog scale. Comparisons between groups were performed using the Student t test and chi(2) test. RESULTS: Twenty incisions in 14 patients were closed with 2-OCA and 20 incisions in 15 patients were closed with subcuticular sutures. Mean time of closure was significantly (P < .005) faster with 2-OCA at 69.50 +/- 33.39 seconds compared with 379.00 +/- 75.39 seconds in the suture group. There was no significant difference in wound complications between the 2 groups; also, there was no significant difference in patient satisfaction and cosmetic outcome of scars at the 3-month follow-up between the 2 groups. CONCLUSIONS: 2-OCA tissue adhesive is an excellent alternative to sutures for effective, reliable, and faster skin closure of maxillofacial incisions. PMID- 24237778 TI - Frontal meningioma incidentally detected in the routine preoperative assessment of tongue cancer: a case report and literature review. AB - Recent advances in diagnostic tools, such as computed tomography and magnetic resonance imaging (MRI), have provided clinicians with the opportunity to detect asymptomatic meningiomas. This report describes a case of frontal convexity meningioma detected incidentally at MRI during the preoperative assessment of tongue cancer. To the best of the authors' knowledge, this case report is the first regarding the successful treatment of tongue cancer in a patient with incidental meningioma. The incidence, perioperative management, and various imaging tests to detect meningiomas are discussed, with a review of the literature. PMID- 24237779 TI - Large carcinoma ex pleomorphic adenoma of the parotid gland: a case report and review of literature. AB - Pleomorphic adenoma (PA) is one of the most common benign tumors of the parotid gland. PA usually grows slowly and is painless. Surgery is necessary for treating PA. Facial palsy, salivary fistula, and Frey syndrome have been reported as complications of tumor resection. PA can transform into a carcinoma ex pleomorphic adenoma (CXPA) over time and as it enlarges. This report describes a case of a large CXPA that transformed from a PA that had developed over 17 years and caused withdrawal from social contact because fear of surgery made the patient refuse treatment. The tumor gradually enlarged without any pain for a decade, but rapid growth and bleeding began a year before admission. Postoperative facial function and local control of the tumor were excellent, but the patient required adjuvant chemotherapy for lung and mediastinum lymph node metastasis leading to dyspnea from tracheal stenosis. This case indicates the importance of adequate explanation and advice when choosing therapy for PA, especially given the risk of a PA transforming to a CXPA. PMID- 24237780 TI - Conventional treatment after myocardial infarction in routine clinical practice results in regression of left common carotid intima-media thickness. AB - This study aimed to evaluate the effect of standard medical treatment on the progression of atherosclerosis after a myocardial infarction, in an ordinary clinical setting, by measuring the right and left common carotid intima-media thickness (IMT). The first investigation took place 3-12 months after the index event; the second took place 3.3-8.2 years after the first. In both investigations, the right and left carotid arteries of 102 patients were examined with an ultrasound duplex scanner. Common carotid IMT and calculated cross sectional intima-media area (cIMa) were measured on both sides. More than 90% of the patients were treated with aspirin, beta-blockers and statins. In the first investigation, IMT and cIMa were significantly greater on the left side compared to the right (IMT: 0.83 +/- 0.22 and 0.74 +/- 0.18 mm, P<0.001; cIMa: 18.2 +/- 5.2 and 16.3 +/- 5.1 mm(2) , P<0.001). In the second investigation, IMT on the left side was significantly reduced compared to the first investigation (0.79 +/- 0.22 and 0.83 +/- 0.22 mm, P<0.05) with a corresponding tendency towards a decrease in cIMa on the same side. In our study, conventional medical treatment after a myocardial infarction in ordinary clinical routines resulted in regression of the common carotid IMT on the left side. The significant side difference in IMT emphasizes the importance of where and how the carotid IMT is measured in studies using this surrogate end point. PMID- 24237781 TI - Evaluation of the fully automated hematological analyzer Mindray BC 6800: comparison with Horiba ABX Pentra DX120. PMID- 24237785 TI - Review of contributions from HDSSs to research in sexual and reproductive health in low- and middle-income countries. AB - OBJECTIVE: To evaluate the contributions of the INDEPTH Network of health and demographic surveillance system (HDSS) members to research efforts and interventions on reproductive health in low- and middle-income countries (LMICs). METHODS: Review of peer-reviewed published papers on sexual and reproductive health (SRH) that use the HDSS framework through (i) an online search for publications using terminology related to HDSS, HIV, Maternal health, adolescent sexual and reproductive health, family planning/contraceptives and fertility, and (ii) asking INDEPTH member centres for information on their published papers on SRH publications that used the HDSS framework. A paper was included in the review only if it used HDSS data, dealt with SRH issues, and had been published in a peer-reviewed international journal. RESULTS: Most of the papers in the review focused on HIV, maternal health, family planning and adolescent sexual and reproductive health (ASRH). Generally, people are knowledgeable about HIV. School attendance considerably delays entry into motherhood and reduces the probability of entering into early marriage or sexual union. The general decline in maternal mortality over the last decade is partly due to better access to emergency obstetric services, improved education of women and reduction in fertility. CONCLUSION: Sexual and reproductive health is a significant public health need, yet little research has been published in this area to inform policy. The HDSS framework is ideal for SRH research, as it offers the advantage to track and monitor progress of relevant health and demographic indicators, especially in family planning, marriage and fertility studies. PMID- 24237786 TI - Obesity, diabetes and pneumonia: the menacing interface of non-communicable and infectious diseases. AB - OBJECTIVES: To review current knowledge on the epidemiological, clinical and biological impact of the pandemic of obesity and diabetes on pneumonias. METHODS: We conducted a literature review using PubMed and EMBASE, supplemented by various sources. Given the disparate and fragmented nature of the literature, a formal systematic review was not possible. RESULTS: In 2008, globally 10% of men and 14% of women were obese and an estimated 371 million had diabetes; half undiagnosed and many obese. Numbers are rising rapidly in low- and middle-income countries where the majority reside, but reliable data are lacking. The most frequent pneumonias in obesity and diabetes are tuberculosis, influenza and pneumococcal, staphylococcal and opportunistic pathogens. Diabetes impacts tuberculosis control and increases drug resistance and mortality. Mortality and morbidity from pneumococcal pneumonia and influenza are increased in obesity and diabetes. In addition to mechanical and physiological effects, there are considerable immunological abnormalities characterised by chronic, low-grade inflammation. Simultaneous up-regulation and dysregulation of both innate and adaptive immune responses impair control and killing of invading organisms. Prevention in those at risk is poorly practised, although screening for tuberculosis in diabetes is beginning in high-burden settings. CONCLUSIONS: Pneumonia is a threat globally in obesity and diabetes with increased incidence and severity of disease. There is uncertainty about whether vaccines are equally effective in those with obesity and diabetes. Increased epidemiological, clinical and biological knowledge will be crucial to face this 21st century challenge. PMID- 24237787 TI - The meaning of life and health experience for the Chinese elderly with chronic illness: a qualitative study from positive health philosophy. AB - Ageing and the concurrent prevalence of chronic disease in older adults produce a great burden and challenge for family, society and individuals. There is a definite need to build the science about caring for older Chinese adults from their perspective to inform health-care professionals. The aim of the study was to investigate the meaning of life and health experience of Chinese elderly with chronic illness and identify health potential from a positive perspective. A qualitative descriptive study was undertaken to interview 11 older adults ages 64 92 in a day centre. In 2011, the data were collected and analysed by thematic analysis. Four interrelated themes indicated a rich meaning of life and health experience from the older adults: (i) happiness lies in contentment; (ii) sense of responsibility; (iii) letting nature take its course; (iv) and proactive self balance. These interrelated themes with partial conflict presented a dialectic meaning of life and were interpreted from traditional Chinese culture and compared with positive health philosophy. The significance of finding will encourage nursing practice work with clients and identify the potential and self help strength of the elderly. PMID- 24237784 TI - Epidemiology of ocular surface squamous neoplasia in Africa. AB - OBJECTIVES: To describe the epidemiology and an aetiological model of ocular surface squamous neoplasia (OSSN) in Africa. METHODS: Systematic and non systematic review methods were used. Incidence was obtained from the International Agency for Research on Cancer. We searched PubMed, EMBASE, Web of Science and the reference lists of articles retrieved. Meta-analyses were conducted using a fixed-effects model for HIV and cigarette smoking and random effects for human papilloma virus (HPV). RESULTS: The incidence of OSSN is highest in the Southern Hemisphere (16 degrees South), with the highest age standardised rate (ASR) reported from Zimbabwe (3.4 and 3.0 cases/year/100 000 population for males and females, respectively). The mean ASR worldwide is 0.18 and 0.08 cases/year/100 000 among males and females, respectively. The risk increases with exposure to direct daylight (2-4 h, OR = 1.7, 95% CI: 1.2-2.4 and >=5 h OR = 1.8, 95% CI: 1.1-3.1) and outdoor occupations (OR = 1.7, 95% CI: 1.1 2.6). Meta-analysis also shows a strong association with HIV (6 studies: OR = 6.17, 95% CI: 4.83-7.89) and HPV (7 studies: OR = 2.64, 95% CI: 1.27-5.49) but not cigarette smoking (2 studies: OR = 1.40, 95% CI: 0.94-2.09). The effect of atopy, xeroderma pigmentosa and vitamin A deficiency is unclear. CONCLUSIONS: Africa has the highest incidence of OSSN in the world, where males and females are equally affected, unlike other continents where male disease predominates. African women probably have increased risk due to their higher prevalence of HIV and HPV infections. As the survival of HIV-infected people increases, and given no evidence that anti-retroviral therapy (ART) reduces the risk of OSSN, the incidence of OSSN may increase in coming years. PMID- 24237788 TI - Attitude of elderly patients towards cardiopulmonary resuscitation in Greece. AB - AIM: Although researchers in several countries have investigated patients' points of view regarding cardiopulmonary resuscitation, there has been no research investigating this issue in Greece. The present study aimed at identifying the attitude of older Greek patients regarding cardiopulmonary resuscitation. METHODS: One basic questionnaire consisting of 34 questions was used in order to identify patients' opinions regarding cardiopulmonary resuscitation in five different hospitals from June to November 2011. RESULTS: In total, 300 questionnaires were collected. Although patients' knowledge regarding cardiopulmonary resuscitation was poor, most of them would like to be resuscitated in case they suffered an in-hospital cardiac arrest. Also, they believe that they should have the right to accept or refuse treatment. However, the legal and sociocultural norms in Greece do not support patients' choice for the decision to refuse resuscitation. The influence of several factors, such as their general health status or the underlying pathology, could lead patients to give a "do not attempt resuscitation" order. CONCLUSIONS: The attitudes of older Greek patients regarding resuscitation are not different from others', whereas the legal and sociocultural norms in Greece do not support patient choice in end of-life decisions, namely the decision to refuse resuscitation. We advocate the introduction of advanced directives, as well as the establishment and implementation of specific legislation regarding the ethics of resuscitation in Greece. PMID- 24237789 TI - Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement. AB - Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID- 24237790 TI - Study design: two long-term observational studies of the biosimilar filgrastim NivestimTM (Hospira filgrastim) in the treatment and prevention of chemotherapy induced neutropenia. AB - BACKGROUND: NivestimTM (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. NivestimTM has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen(r). Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of NivestimTM for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. METHODS/DESIGN: The NEXT (Tolerance de Nivestim chez les patiEnts traites par une chimiotherapie anticancereuse cytotoXique en praTique courante) and VENICE (VErtraglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of NivestimTM in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of NivestimTM by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of NivestimTM therapy (including chemotherapy dose intensity), patterns of use of NivestimTM, and physician knowledge regarding filgrastim prescription and the reasons for choosing NivestimTM. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. DISCUSSION: The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving NivestimTM to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of NivestimTM in patients encountered in the general patient population. TRIAL REGISTRATION: NEXT NCT01574235, VENICE NCT01627990. PMID- 24237792 TI - Managing cancer-related fatigue in men with prostate cancer: a systematic review of non-pharmacological interventions. AB - The aim of this systematic review was to synthesize the best available evidence informing the effectiveness of non-pharmacological interventions for managing cancer-related fatigue in men treated for prostate cancer. This review considered experimental studies that included men with prostate cancer (regardless of staging, previous treatment or comorbidities), aged 18 years and over who were undergoing any treatment, or had completed any treatment for prostate cancer within the previous 12 months. Three interventions were identified for the management of cancer-related fatigue in men with prostate cancer. Evidence from five studies including 447 participants demonstrates the effectiveness of physical activity, both aerobic and resistance exercise, and from three studies including 153 participants suggesting the benefits of psychosocial interventions including education and cognitive behavioural therapy. Health professionals require knowledge of a range of effective interventions aimed at reducing cancer related fatigue in men with prostate cancer and should incorporate those interventions into their patient management. Although physical activity appears to show the greatest benefit, other non-pharmacological interventions such as education and cognitive behavioural therapy have demonstrated benefit and should also be considered as a strategy in treating this debilitating side effect of cancer and its treatment. PMID- 24237791 TI - Co-targeting the PI3K/mTOR and JAK2 signalling pathways produces synergistic activity against myeloproliferative neoplasms. AB - Aberrant JAK2 signalling plays a central role in myeloproliferative neoplasms (MPN). JAK2 inhibitors have proven to be clinically efficacious, however, they are not mutation-specific and competent enough to suppress neoplastic clonal haematopoiesis. We hypothesized that, by simultaneously targeting multiple activated signalling pathways, MPN could be more effectively treated. To this end we investigated the efficacy of BEZ235, a dual PI3K/mTOR inhibitor, alone and in combination with the JAK1/JAK2 inhibitor ruxolitinib, in different preclinical models of MPN. Single-agent BEZ235 inhibited the proliferation and induced cell cycle arrest and apoptosis of mouse and human JAK2V617F mutated cell lines at concentrations significantly lower than those required to inhibit the wild-type counterpart, and preferentially prevented colony formation from JAK2V617F knock in mice and patients' progenitor cells compared with normal ones. Co-treatment of BEZ235 and ruxolitinib produced significant synergism in all these in-vitro models. Co-treatment was also more effective than single drugs in reducing the extent of disease and prolonging survival of immunodeficient mice injected with JAK2V617F-mutated Ba/F3-EPOR cells and in reducing spleen size, decreasing reticulocyte count and improving spleen histopathology in conditional JAK2V617F knock-in mice. In conclusion, combined inhibition of PI3K/mTOR and JAK2 signalling may represent a novel therapeutic strategy in MPN. PMID- 24237793 TI - Exhaled nitric oxide is related to atopy, but not asthma in adolescents with bronchiolitis in infancy. AB - BACKGROUND: The fraction of exhaled nitric oxide (FeNO) has been suggested as a non-invasive marker of eosinophilic inflammation in asthma, but lately rather as a biomarker of atopy than of asthma itself. Asthma after bronchiolitis is common up to early adolescence, but the inflammation and pathophysiology may differ from other phenotypes of childhood asthma. We aimed to assess if FeNO was different in children with former hospitalization for bronchiolitis and a control group, and to explore whether the role of FeNO as a marker of asthma, atopy or bronchial hyperresponsiveness (BHR) differed between these two groups of children. METHODS: The study included 108 of 131 children (82%) hospitalized for bronchiolitis in 1997-98, of whom 82 (76%) had tested positive for Respiratory syncytial virus, and 90 age matched controls. The follow-up took place in 2008-2009 at 11 years of age. The children answered an ISAAC questionnaire regarding respiratory symptoms and skin prick tests, spirometry, methacholine provocation test and measurement of FeNO were performed. RESULTS: Analysed by ANOVA, FeNO levels did not differ between the post-bronchiolitis and control groups (p = 0.214). By multivariate regression analyses, atopy, height (p < 0.001 for both) and BHR (p = 0.034), but not asthma (p = 0.805) or hospitalization for bronchiolitis (p = 0.359), were associated with FeNO in the post-bronchiolitis and control groups. The associations for atopy and BHR were similar in the post-bronchiolitis and in the control group. CONCLUSION: FeNO did not differ between 11 year old children hospitalized for bronchiolitis and a control group. FeNO was associated with atopy, but not with asthma in both groups. PMID- 24237794 TI - Pseudoaneurysm originating from left ventricle aneurysm: an autopsy case and review of literature. AB - Rupture of the free wall of the left ventricle is a catastrophic complication of acute myocardial infarction. Rarely, free wall rupture is contained by overlying adherent pericardium, producing a pseudoaneurysm of the left ventricle. In this report, a case of a left ventricular pseudoaneurysm due to a previous myocardial infarction is described. A 55-year-old woman had a severe chest pain 11 months prior to death. No cardiac investigation was performed. Three days prior to death, she suffered from fatigue and weakness, and had a witnessed sudden cardiac death. At autopsy, a 8.5 * 10 * 8 cm pseudoaneurysm of the left ventricle was found. There was severe coronary artery atherosclerosis. There were extensive adhesions between pericardium and pseudoaneurysm wall. The cause of death was attributed to heart failure and resulting arrhythmia. The case illustrates the rare event of left ventricular pseudoaneurysm first diagnosed at forensic autopsy. PMID- 24237795 TI - Sheep shearing and sudden death. AB - A 29-year-old sheep shearer collapsed after walking across a shearing shed floor, holding his hand over an incised wound to his neck. Attempted resuscitation was unsuccessful. At the death scene fine arterial blood spatter was noted and at autopsy a single incised wound to the neck was observed, the patterned edges of which corresponded to the teeth of the shears. Dissection revealed injury to the underlying jugular vein and the mid portion of the common carotid artery. Death was attributed to blood loss from an incised wound of the left side of the neck. This case demonstrates the rare event of an accidental death related to the actions of a sheep. Although a relatively small animal, review of the circumstances and interviews with those present revealed that sudden and unexpected movement of the sheep during shearing had caused the shearer to lose control of his electrical shears resulting in a lethal incised wound to the neck. The blood spatter pattern at the scene was supportive of both witness descriptions and the findings at autopsy. PMID- 24237796 TI - Estimation of stature by using lower limb dimensions in the Malaysian population. AB - Estimation of stature is an important step in developing a biological profile for human identification. It may provide a valuable indicator for an unknown individual in a population. The aim of this study was to analyse the relationship between stature and lower limb dimensions in the Malaysian population. The sample comprised 100 corpses, which included 69 males and 31 females between the age range of 20-90 years old. The parameters measured were stature, thigh length, lower leg length, leg length, foot length, foot height and foot breadth. Results showed that the mean values in males were significantly higher than those in females (p < 0.05). There were significant correlations between lower limb dimensions and stature. Cross-validation of the equation on 100 individuals showed close approximation between known stature and estimated stature. It was concluded that lower limb dimensions were useful for estimation of stature, which should be validated in future studies. PMID- 24237797 TI - Forensic investigation of suicide cases in major Greek correctional facilities. AB - INTRODUCTION: According to Greek legislation the medico-legal investigation of deaths occurring in prisons is mandatory. Furthermore, in cases of suicide or of suspected suicide the contribution of medico-legal investigation is of grave importance. The current paper addresses the medico-legal investigation of suicide cases in Greek correctional facilities and aims to describe the current situation. MATERIALS & METHODS: Our study consists of the meticulous research in the data records of major Greek correctional facilities, for the time period 1999 2010. Official permission was obtained by the Hellenic Ministry of Justice, which provided us the access to the records. Data was also collected from the Piraeus Forensic Service, from the Department of Pathological Anatomy of the University of Athens and finally from our own records. Measures were taken to respect the anonymity of the cases. Data was collected for the social, penal, medical history as well as for the medico-legal investigation. RESULTS-CONCLUSIONS: It appears that 85.7% of suicide cases were transferred to the Prisoner's Hospital (p < 0.0001), the forensic pathologist who conducted the PME did not perform scene investigation in none of the 70 suicide cases. In a total of 70 cases, histopathological examination, was requested only in 30 cases (42.9%). Hanging was the preferred method for those who committed suicide, followed by the poisoning due to psychoactive substances. Understanding the mistakes made during the forensic investigation of suicide cases inside correctional facilities is necessary, in order to prevent them from occurring again in the future, by implementing appropriate new policies and guidelines. PMID- 24237798 TI - Pattern and outcome of Cleistanthus collinus (Oduvanthalai) poisoning in a tertiary care teaching hospital in South India. AB - There is paucity of information on human studies about Cleistanthus collinus (Oduvanthalai) poisoning at global level. The present study was done to find out the pattern and outcomes with acute poisoning of this plant poison. Retrospective record based study was conducted among acute C. collinus (Oduvanthalai) poisoning cases admitted between January 2010 and December 2010 in a tertiary care teaching hospital in South India. A total of 51 cases were analyzed with 52.9% of them being females and 51% belonged to 21-40 years age group. Interpersonal conflict was the stressor for poisoning in 76% cases. Mortality rate was 17.6% with a median duration of 3.5 days from time of ingestion. Majority of the patients who died during hospitalization had ingested decoction (77.8%), and had neurological manifestations (77.8%), hypokalemia (77.8%), neutrophilia (66.7%), leucocyotosis (55.6%) and elevated blood urea (77.8%). It was found that lower potassium level, white blood cell and neutrophil count were significantly associated with mortality due to poisoning. PMID- 24237799 TI - Acute fatal poisoning with Tolfenpyrad. AB - The authors present a fatal case of poisoning with Tolfenpyrad (TFP), a pesticide first approved in Japan in 2002. A man in his fifties was found dead in the supine position at his son's home and the small towel with a smell of naphthalene was found nearby. Forensic autopsy was unremarkable, except for a very small amount of light pink fluid in the stomach, with naphthalene odour. The toxicological analyses revealed the presence of TFP and its major metabolite PTCA (4-[4-[(4-chloro-3-ethyl-1-methylpyrazol-5-yl)carbonylaminomethyl]phenoxy]benzoic acid), together with naphthalene and methyl naphthalenes in the post-mortem sample, with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) respectively. The plasma concentrations of each substance were quantified as 1.97 MUg/ml (TFP), 2.88 MUg/ml (PTCA), 1.70 MUg/ml (naphthalene), 0.67 MUg/ml (1-methyl naphthalene) and 1.44 MUg/ml (2 methyl naphthalene). According to these results together with autopsy findings, the cause of his death was determined to be acute Tolfenpyrad poisoning. This is the first case report of fatal poisoning attributable to an intake of TFP product. PMID- 24237800 TI - Medico-legal significance of the identification of offending snake in a fatal snake bite: a case report. AB - A 19 year old male was admitted to a tertiary care centre in Sri Lanka, with a history of snake bite while sleeping at night. A killed specimen of a snake was brought with the patient. It had been identified as a non-venomous snake by the doctor and handed over to relatives, with a comment to that effect. Patient had no clinical or laboratory evidence of envenoming on admission. Patient developed bilateral ptosis six hours after alleged snake bite, soon followed by respiratory paralysis and was treated with Indian polyvalent anti-venom serum. After 12 h of the bite, patient had developed hypotension that did not respond to ionotropes. Despite intensive management, patient had become deeply comatose and deceased 46 h following the snake bite. Autopsy revealed features suggestive of disseminated intravascular coagulation. Since an allegation of medical negligence too had been levelled by the relations of the patient against the clinical staff, the buried specimen of the snake was recovered by police, on a judicial order, a week later. It was found to be almost completely disintegrated and only the scales and bones were remaining. According to the scale characters, the reconstructed specimen was identified as Indian krait (Bungarus caeruleus). Authentication of snake is important in investigating a death due to snake bite, especially when the snake was initially claimed to be a non-venomous snake. This case suggests the usefulness of forensic identification of species of the snake in investigating suspected snake bite cases. PMID- 24237801 TI - Characteristics of cardiovascular deaths in forensic medical cases in Budapest, Vilnius and Tallinn. AB - Evaluation of the pathomorphological characteristics of cases involving natural and sudden cardiovascular death is essential for the determination of the cause of death. The main purpose of this study is to investigate sudden unexpected cardiovascular death and to study how different geographical climatic influences may affect cardiac mortality in three capitals: Budapest, Vilnius and Tallinn. There were 8482 (5753 male, 2729 female) cardiovascular deaths between 2005 and 2009. The highest rate was observed in the age group between 71 and 80 years (35.17%) and 51-60 years (24.45%). The highest number of cardiovascular deaths occur in January (805/9.49%) and December (770/9.07%). Seasonal distribution was observed, with winter prevalence in Tallinn (279/3.20%) and spring prevalence in Vilnius (760/8.90%). Though in Vilnius and Budapest a great number of deaths occurred in winter and spring, any correlation with other factors (e.g. age, gender, BAC) was not statistically significant. Based on our results we can conclude that environmental-geographical parameters may affect natural cardiovascular death. Examination of pathological patterns and predisposing environmental parameters may help to improve prevention strategies. PMID- 24237802 TI - Intracranial penetrating injury by screw driver: a case report and review of literature. AB - Penetrating injury to the head, with the exception of missile injuries is rare owing to thick calvarium. Orbital and temporal areas are comparatively vulnerable to penetrating injuries, due to their relative thinness. A case is presented in which a man killed his wife by forcefully thrusting a screw driver into her cranial cavity. The deceased presented to the hospital with the screw driver embedded in her head. She was declared as 'brought dead on arrival' at the emergency of the hospital. Pre-autopsy plain radiography and Computed Tomography (CT) of the head were done to assess the extent of brain damage. The peculiarity of this case lies in the fact that screw driver as a stabbing weapon in the head is very rarely used. In such cases, there is a need to perform radiography and CT with the weapon in-situ for better interpretation on injuries. In this paper role of radiography and CT in intra cranial penetration is discussed with review of literature. PMID- 24237803 TI - Blood alcohol concentration of suicide victims by partial hanging. AB - During the investigated period, 2000-2007, 4249 suicides were reported in Slovenia, and 1061 autopsies of suicide deaths from the central, northwestern, and southwestern parts of Slovenia were conducted at the Institute of Forensic Medicine in Ljubljana. To identify a possible role of alcohol use in the selection of suicide method blood samples were collected during medicolegal autopsies of suicide victims in order to establish their blood alcohol concentration (BAC) level at the time of death. The study group consisted of 844 suicide victims that used violent suicide methods and 174 suicide victims that used non-violent suicide methods. Out of the group with violent suicide methods 184 (21.8%) suicide victims by partial hanging and 112 (13.3%) suicide victims by complete hanging were identified. The average age was higher in the group of suicide victims by partial hanging than in the group of suicide victims by complete hanging (p < 0.001; T = 3653; df = 294). The mean BAC was higher (T = 1.604; df = 278; p < 0.05) in the group of suicide victims by partial hanging (0.57 g/kg; SD +/- 0.92) than in the group of suicide victims by complete hanging (0.40 g/kg; SD +/- 0.82). The proportion of BAC positive suicide victims with blood alcohol concentration above 0.1 g/kg at the time of death was higher in the group of suicide victims who used non-violent suicide methods in comparison to the group of suicide victims who used violent suicide methods (p < 0.001; chi(2) = 14.988, df = 1). Partial hanging was almost twice as common as complete hanging. Higher BAC in the group of suicide victims by partial hanging and more BAC positive suicide victims in the group who died by non-violent suicide methods could give indications about the role of alcohol in the selection of suicide method. PMID- 24237804 TI - Fitness for detention in police custody: a practical proposal for improving the format of medical opinion. AB - Health issues among arrestees are a worldwide concern for which only local policies have been established. Physicians attending detainees in police custody are expected to decide whether the detainee's health status is compatible with detention in a police station and make any useful observations. A high degree of heterogeneity in the information collected by the physician and transmitted to the police has been observed. We analyzed the content and limitations of available documents and developed a model that could serve as a guide for any attending physician. The document presented here has been used in France on over 50,000 occasions since June 2010. We developed a two-page template consisting of (1) a standard medical certificate to be sent to the authority who requested the doctor's attendance and (2) a confidential medical record, not sent to the requesting authority. We evaluated perceived health by the three global health indicators of the Minimum European Health Module and used DSM IV criteria for the evaluation of addictive disorders. In the case of recent traumatic injuries, the certificate has also included the collection of data on traumatic injuries and the contexts of their occurrence. The proposed certificate achieved several goals, by protecting the interests of the person examined, in case of poor conditions of arrest or detention, protecting doctors in cases of legal proceedings, and allowing epidemiological data to be collected. The certificate may also contribute to an international awareness of medical care for detainees in police custody. PMID- 24237805 TI - The comparison of disposal attitudes towards forensic psychiatric patients among police officers, psychiatrists and community members in China. AB - OBJECTIVE: To understand disposal attitudes towards forensic psychiatric patients among police officers, psychiatrists and community members in China. METHOD: 118 community members, 121 psychiatrists and 105 police officers completed a questionnaire regarding disposal attitudes towards forensic psychiatric patients. RESULT: Surveyed respondents (87.4%) believed patients with mental disorders experienced discrimination, and 97.4% were in favor of providing livelihood security for them. Police officers (89.5%) agreed that patients with mental illness were more violent than the general population, which was significantly higher than 74.4% of psychiatrists (X(2) = 14.29, P = 0.000). Among three groups, the most preferred disposal option for those found not guilty by reason of insanity (NGRI) was to treat them in the custody of a forensic psychiatric hospital, such as an Ankang Hospital (86.9%). The respondents agreed (96.8%) that an independent review board should be established for disposing decisions for forensic psychiatric patients. The percentage who agreed that police officers, prosecutors, and judges should be included in the review board was significantly higher among police officers than among community members (x(2) = 6.60, P = 0.01; x(2) = 9.74, P = 0.002; x(2) = 7.38, P = 0.007). When asked, "who has the legal right to determine whether offenders with mental disorders should bear criminal responsibility", forensic psychiatrists and judges were the top two responders (79.5% and 63.4%, respectively). CONCLUSION: This study suggested that the majority of those surveyed, especially police officers, held that patients with mental illness were violent and should receive violence risk assessments. Although psychiatrists paid more attention to the rights of patients, they also lacked legal knowledge, similar to community members and police officers. Therefore, it is necessary to inform the public regarding mental health, and to provide legal knowledge. PMID- 24237806 TI - The effect of the prone maximal restraint position with and without weight force on cardiac output and other hemodynamic measures. AB - BACKGROUND: The prone maximal restraint (PMR) position has been used by law enforcement and emergency care personnel to restrain acutely combative or agitated individual. The position places the subject prone with wrists handcuffed behind the back and secured to the ankles. Prior work has indicated a reduction in inferior vena cava (IVC) diameter associated with this position when weight force is applied to the back. It is therefore possible that this position can negatively impact hemodynamic stability. OBJECTIVES: We sought to measure the impact of PMR with and without weight force on measures of cardiac function including vital signs, oxygenation, stroke volume (SV), IVC diameter, cardiac output (CO) and cardiac index (CI). METHODS: We conducted a randomized prospective cross-over experimental study of 25 healthy male volunteers (22-43 years of age) placed in 5 different body positions: supine (SU), prone (PR), prone maximal restraint with no weight force (PMR-0), prone maximal restraint with 50 lbs added to the subject's back (PMR-50), and prone maximal restraint with 100 lbs added to the subject's back (PMR-100) for 3 min. Heart rate (HR), blood pressure (BP), and oxygenation saturation (O2 sat) were monitored. In addition, echocardiography was performed to measure left ventricular outflow tract diameter (LVOTD), and SV, CO, and CI were then calculated. Data were analyzed using repeated measures ANOVA with pair-wise comparisons when appropriate to evaluate changes with each variable with respective positioning. RESULTS: Despite a small decrease in SV between SU and PMR positions, there were no statistically significant differences in CO between the 5 different positions. There were also no differences in CI between positions other than a small decrease when comparing SU and PMR-50 only (mean difference -0.39 L/stroke, p = 0.005). There was no evidence of hemodynamic compromise in any of the PMR positions when evaluating HR, MAP or O2 sat. CONCLUSIONS: PMR with and without weight force did not result in any changes in CO or other evidence of cardiovascular or hemodynamic compromise. PMID- 24237807 TI - What is the appropriate approach in sex determination of hyoid bones? AB - The hyoid bone is characterized by sexually dimorphic features, enabling it to occasionally be used in the sex determination aspect of establishing the biological profile in skeletal remains. Based on a sample of 298 fused and non fused hyoid bones, the present paper compares several methodological approaches to sexing human hyoid bones in order to test the legitimacy of osteometrics-based linear discriminant equations and to explore the potentials of symbolic regression and methods of geometric morphometrics. In addition, two sets of published predictive models, one of which originated in an indigenous population, were validated on the studied sample. The results showed that the hyoid shape itself is a moderate sex predictor and a combination of linear measurements is a better representation of sex-related differences. The symbolic regression was shown to exceed the predictive powers of linear discriminant function analysis when two models based on a logistic and step regression reached 96% of correctly classified cases. There was a positive correlation between discriminant scores and an individual's age as the sex assessment was highly skewed in favour of males. This suggests that the human hyoid undergoes age-related modifications which facilitates determination of male bones and complicates determination of females in older individuals. The validation of discriminant equations by Komenda and Cerny (1990) and Kindschud et al. (2010) revealed that there are marked inter population and inter-sample differences which lessened the power to correctly determine female hyoid bones. PMID- 24237808 TI - The subpubic angle in sex determination: anthropometric measurements and analyses on Anatolian Caucasians using multidetector computed tomography datasets. AB - INTRODUCTION AND AIM: The investigation of new anatomical criteria and revalidation of existing ones in sex determination for different populations are among main research foci of forensic anthropometry. In that context, the pelvis is the most extensively studied bone. A number of qualitative classifications, dimensional measurements and indices have been proposed for investigative anthropometry and forensic studies. Independent use of these parameters generally provided an accuracy rate of 70-75%. In this study, the accuracy rate of the subpubic angle in sex determination was investigated in living Anatolian Caucasians. MATERIAL AND METHOD: The subpubic angle was identified and measured on three-dimensional computed tomographic images of pelves. Data were obtained using 64-detector computed tomography (MDCT) with an isotrophic resolution of 500 MUm. The sample included 66 males (41.6 +/- 14.9 years of age) and 43 females (41.1 +/- 14.2 years of age). Measurements were taken on a dedicated three dimensional image analysis workstation. The subpubic angle was electronically measured. The technique and methodology was validated on a standard skeletal model. Intraobserver agreement was analyzed with intraclass correlation coefficient, and intraobserver variability was evaluated with technical error of measurement (inter- and intra-observer TEM), relative technical error of measurement (rTEM) and coefficient of reliability (R) measures. The subpubic angle for the study group and for both sexes was reported as minimum-maximum (mean +/- SD). Independent-Samples T Test for equality of means was used to determine the difference between the two sexes regarding the subpubic angle. The correlation between the subpubic angle and the age of subjects were using Pearson Correlation Coefficients in males and in females. Logistic regression model was used to classify subjects according to their sex. Receiver operating characteristic curve analysis was performed to determine a cut-off value for further studies and to test the performance of the binary classification test. RESULTS: Intraclass correlation for the subpubic angle (0.990), TEM (1082), rTEM (1.492), and R (0.990) represented almost complete reliability and accuracy of the measurement method. The subpubic angle was between 48 degrees and 81 degrees (65.9 degrees +/- 7.2 degrees ) in males and was between 64 degrees and 100 degrees (82.6 degrees +/- 7.7 degrees ) in females. Statistically significant difference was found between males and females regarding the subpubic angle (p < 0.0001). The subpubic angle was not significantly correlated with age in males (p = 0.953), or in females (r = 0.975). The accuracy of the subpubic angle in sex determination was 90.8%. With a cut-off value of 74 degrees , sensitivity of subpubic angle to detect female phenotype was 88% and its specificity was 95%. CONCLUSION: The subpubic angle is an accurate parameter in sex determination with high sensitivity and specificity. PMID- 24237809 TI - Atypical suicides or the first undiagnosed autoerotic deaths in Europe? AB - Autoerotic accidental deaths (AAD) are increasingly reported deaths occurring during solitary sexual rituals used to enhance sexual excitement. The majority of these fatalities involve hanging or other form of self-inflicted asphyxia. The German medical literature, with the first recognized AAD published in the early 1900s, has antedated by decades the first significant AAD reports (1950-1953) in English. Early contributions in languages other than English and German are mostly overlooked in current AAD reviews, although AAD were recognised in some European countries as early as the 1940s and 1950s. For a variety of reasons, it is likely that, before the description of the first AAD in the medical literature, some asphyxia deaths have been classified as suicides with peculiar features, instead of as accidents resulting from life-threatening sexual practices. In the present study, we review and comment on three such atypical asphyxia deaths investigated in central Europe (Austria, Italy, Switzerland) during the period 1821 to 1927. The retrospective analysis of these cases revealed some circumstantial and individual features which nowadays could be linked to AAD, and disclosed the reluctance of medical examiners to analyse their motivational, and possibly sexual, background. The medico-legal approach to some autopsy findings of these cases also illustrates some controversial diagnostic issues regarding mechanical asphyxia, issues recurrently debated during the 19th century. PMID- 24237810 TI - Autopsy proven causes of in hospital mortality in acute stroke. AB - To characterize discrepancies between the causes of death as determined by the clinician and autopsy findings in patients admitted with stroke, we retrospectively reviewed all autopsies on patients died with a diagnosis of stroke. Fifty-eight patients with a diagnosis of stroke died after admission to our tertiary medical center in the past ten years were autopsied. Strokes included ischemic strokes, hemorrhagic strokes and subarachnoid hemorrhages. Thirty-five had complete autopsy and twenty-three patients had autopsy limited to brain only examination. We reviewed the autopsy findings and correlated them to the clinical diagnoses that were extracted from the clinical records. We looked particularly for major discrepancies that could have altered treatment strategies. Discrepancies between clinical diagnoses and autopsy findings were classified into major and minor using the Goldman et al. criteria. Only in three instances there were major discrepancies and therapy may have altered medical management in one of these. PMID- 24237811 TI - Fatal cranial injury in an individual from Messina (Sicily) during the times of the Roman Empire. AB - Forensic and archaeological examinations of human skeletons can provide us with evidence of violence. In this paper, we present the patterns of two cranial lesions found on an adult male (T173) buried in a grave in the necropolis 'Isolato 96', Messina, Sicily, dating back to the Roman Empire (1st century BC - 1st century AD). The skull reveals two perimortem traumatic lesions, one produced by a sharp object on the right parietal bone and the other one on the left parietal bone, presumably the result of a fall. The interpretation of fracture patterns found in this cranium are an illustration of how forensic approaches can be applied with great benefit to archaeological specimens. PMID- 24237812 TI - Lack of impairment due to confirmed codeine use prior to a motor vehicle accident: role of pharmacogenomics. AB - BACKGROUND: We examined forensic serum toxicology and pharmacogenomics data from a woman on codeine shortly before she caused a motor vehicle accident. METHODS: A woman driving erratically collided with a parked car of a highway seriously injuring 2 men working to repair the parked vehicle. The woman tested positive for codeine, acetaminophen and barbital. She had been taking these medications for 20 years due to migraine headache. Serum toxicology and genotype analysis for cytochrome P450, UDP glucuronosyltransferase, and other metabolizing enzymes were measured. RESULTS: The woman was tried and convicted of driving under the influence resulting in bodily harm and was sentenced to 6 years. Toxicology results on peripheral blood showed a total and free codeine of 840 and 348 MUg/L, respectively, and total morphine of 20 MUg/L (17, 3, and 0 MUg/L for morphine-3 glucuronide, morphine-6-glucuronide, and free morphine, respectively). She was heterozygous for CYP 2D6 *2/*4 (extensive/poor metabolism) and heterozygous for UGT 2B7 *1/*2 (extensive/ultra-rapid metabolism). The woman was also taking fluoxetine and bupropion which are strong inhibitors of CYP 2D6. CONCLUSIONS: Based on her genotype and phenotype and reports by the arresting officer, we suggest that the subject in question was not intoxicated by opiates at the time of her motor vehicle accident and may have been falsely incarcerated. PMID- 24237813 TI - Knowledge attitude and practice of pesticide use among agricultural workers in Puducherry, South India. AB - OBJECTIVES: To study the level of knowledge and practice related to pesticides and their adverse effects among agricultural workers. MATERIALS AND METHODS: A cross sectional study among 100 randomly selected agricultural workers, using or ever used pesticide within last one year was conducted in Puducherry, South India. The questionnaire was adapted from WHO field surveys of 'Exposure to Pesticides Standard Protocol' and similar studies. Data were collected by face to face interview. RESULTS: All the participants were male with mean age of 54.3 yrs. While 70% of respondents perceived pesticide spraying affects a person's health, only 40% were aware that it affects the environment. Two thirds of the respondents (62%) were aware that pesticide enters the body through nose and affects lungs. Awareness on other modes of entry was less. Majority (76%) of them was aware of training programs conducted by government agriculture department on pest management. About 42% of farmers had good knowledge regarding pesticide. Between 40% and 70% of respondents were not using any protective equipments during pesticide spraying. Around 68% of farmers indiscriminately disposed empty containers while 48% buried the leftover pesticides. Significant association (p < 0.05) was observed between knowledge of the farmers and their practices related to pesticides. CONCLUSION: Overall awareness of agricultural workers on pesticide was inadequate. Improper disposal of pesticides and its container can produce harm to the environment. The findings of the study emphasize the need to educate agricultural workers regarding safe and adequate use of pesticides to prevent health and environmental hazards. PMID- 24237814 TI - Suicide attempts involving power drills. AB - A 61-year-old man was found dead next to a power drill soiled with blood and bone dust. A 5 mm circular wound of the forehead corresponded to the size of the drill bit. Subarachnoid haemorrhage was present over the anterior pole of the left frontal lobe with a penetrating injury extending 75 mm into the frontal lobe white matter towards, but not involving, the basal ganglia. No major intracranial vessels had been injured and there was no significant intraparenchymal haemorrhage. Death was due to haemorrhage from self-inflicted stab wounds to the abdomen with an associated penetrating intracranial wound from a power drill. Deaths due to power drills are rare and are either accidents or suicides. Wounds caused by power drills may be mistaken for bullet entrance wounds, and the marks around a wound from the drill chuck as muzzle imprints. A lack of internal bevelling helps to distinguish the entrance wound from that due to a projectile. Significant penetration of the brain may occur without lethal injury. PMID- 24237815 TI - Assessment of viable bacteria and bacterial DNA in blood and bloodstain specimens stored under various conditions. AB - Microbial forensic specimens that are collected at biocrime and bioterrorism scenes include blood, tissue, cloths containing biological fluids, swabs, water, soil, and aerosols. It is preferable that pathogens in such specimens are alive and kept in a steady state. Specimens may be stored for a prolonged period before analysis; therefore, it is important to understand the effect of the storage conditions on the pathogens contained within the specimens. In this study, we prepared blood and bloodstain specimens containing Gram-negative or -positive bacteria, stored the samples for 482 days under various conditions, and measured viable bacterial counts and total bacterial contents in the samples. Viable bacteria were preserved well in the samples stored at -30 and -80 degrees C, but were diminished or undetectable in the samples stored at 4 degrees C and room temperature. The total bacterial content was maintained in the blood samples stored at -30 and -80 degrees C and in the bloodstain samples stored under all temperature conditions, but decreased in the blood samples stored at 4 degrees C and room temperature. This study showed that the storage conditions affected viable bacteria and bacterial DNA and that freezing and drying were significant for their long-term storage. We provide important information for the storage of microbial forensic specimens. PMID- 24237816 TI - Estimation of sex from the upper limb measurements of Sudanese adults. AB - Sex estimation is the first biological attribute needed for personal identification from mutilated and amputated limbs or body parts in medical-legal autopsies. Populations have different sizes and proportions that affect the anthropometric assessment of sex. Relatively few published works assess the accuracy of sex estimation from soft tissue measurements of upper limb parts, except for the hand and its components, but these studies involve a limited range of global populations. The current study aimed to assess the degree of sexual dimorphism in upper limb measurements and the accuracy of using these measurements for sex estimation in a contemporary adult Sudanese population. The upper arm length, ulnar length, wrist breadth, hand length, and hand breadth of 240 right-handed Sudanese subjects (120 males and 120 females) aged between 25 and 30 years were measured by international anthropometric standards. Demarking points, sexual dimorphism indices and discriminant functions were developed from 200 subjects (100 males and 100 females) who composed the study group. All variables were sexually dimorphic. The ulnar length, wrist breadth and hand breadth significantly contributed to sex estimation. Forearm dimensions showed a higher accuracy for sex estimation than hand dimensions. Cross-validated sex classification accuracy ranged between 78.5% and 89.5%. The reliability of these standards was assessed in a test sample of 20 males and 20 females, and the results showed accuracy between 77.5% and 90%. This study provides new forensic standards for sex estimation from upper limb measurements of Sudanese adults. PMID- 24237817 TI - A study of psychiatry morbidity and co-morbid physical illness among convicted and awaiting trial inmates in Jos prison. AB - BACKGROUND: Having a psychiatric diagnosis is still considered a major burden in life. In addition to dealing with stigma regarding mental illness, persons with severe mental illness have an added risk of having co-morbid medical illnesses that can further impair their already turbulent life. The importance of detecting co-morbid medical illnesses is to ensure a holistic treatment. This study assessed the prevalence of psychiatric morbidity and co-morbid physical illness among convicted and awaiting trial inmates in Jos prison. METHOD: A cross sectional, descriptive study was carried out among 608 male inmates in Jos maximum security prison, Plateau State, Nigeria. They were screened with self administered GHQ-28 questionnaire and interviewed using CIDI. RESULTS: More than half (57%) of the studied subjects had a psychiatric disorder with substance use disorder as the commonest (48.7%) diagnosis. Physical co-morbidity was found in (18%) of the subjects with infectious disease (A00-A99) as the commonest source 13 (3.7%) of physical co-morbidity among the subjects. A statistically significant relationship was found between psychiatric disorder and co-morbid physical illness (p = 0.000). CONCLUSION: The study showed a high rate of psychiatric morbidity and co-morbid physical illness with infectious disease being the commonest source of physical co-morbidity; and substance use disorder the commonest psychiatric disorder among the prison inmates. PMID- 24237818 TI - Epidemiology & preventive aspects of railway suicides and fatalities related to trespassing accidents. AB - PURPOSE: Suicide and trespass are major contributors to risk on the railway, resulting in around 170-180 fatalities per year in Lucknow region, as well as associated major disruption to the rail network. Lucknow is the capital city of the state of Uttar Pradesh in India. METHODS: The analysis included train pedestrian fatalities during 2007-2012. The data for 2007-2012 were collected from the autopsy reports of the university, case sheets from the hospital, the general prosecutor's investigations report and the inquest reports from police. RESULTS: The results show that the majority of victims were males. Half of the suicide victims were 20-39 years old. Accidents happened most frequently in situations when a person was walking on the tracks/in front of train (22.7%) or were crossing the tracks illegally (20.9%). Among all train-pedestrian fatalities, about half of the victims (42.8%) were intoxicated by alcohol. Female suicide victims suffered from mental health problems more frequently (55.8%) than male suicide victims. CONCLUSION: Overall, there is no reason to believe that train-pedestrian fatalities are unavoidable. By contrast, the effective prevention of railway suicides and accidents should be based on a systems approach involving effective measures introduces by several organisations such as government, railway organisations, various authorities (such as public health, education, enforcement, urban planning) and communities. Same measures can often be used to prevent both trespassing and suicides, even though their effectiveness may depend on the target group. In addition, there are measures specifically targeted to prevent either trespassing or suicides. PMID- 24237819 TI - Socioeconomic, demographic study on substance abuse among students of professional college in a southern town, Berhampur of Odisha state (India). AB - Currently there is an increasing trend of substance abuse in developing countries like India. This study attempted to identify the different predisposing factors, associated psycho-social and medical problems, prevalence and types of substance abuse in students. The study covered a cross-section of 720 students with an overall male to female ratio of 4.1:1. The majority of the sufferers were from middle socioeconomic class, aged between 15 and 19 years. Common substances of abuse were chewable tobacco and cannabis. The risk of abuse was more in hostellers hailing from broken families (62.5%). Friends had the highest influence (59%). Most of them (49.4%) tried multiple times to give up, but peer pressure (53%) compelled them to restart. In 60.8% cases the parents were completely unaware about this behavior. The commonly associated problems were psychological (34.3%) and medical (29.5%). Our study at the end points out major risk factors and their remedial measures to curb substance abuse. PMID- 24237820 TI - Sudden death of a young woman attributed to diabetic ketoacidosis. AB - A young woman's death at home was attributed to new onset diabetic ketoacidosis with subsequent litigation supported by several expert consultants, despite a history and postmortem findings inconsistent with this diagnosis. More thorough tissue study of the heart and analysis of the circumstances led to a credible explanation of the entire scenario. PMID- 24237821 TI - The value of 100% retrospective peer review in a forensic pathology practice. AB - Peer review in forensic pathology practice has become an important cornerstone of continuous quality improvement. Although there are several components to an effective and transparent peer review process, one of the most essential is the review of completed reports. The autopsy report may be reviewed prospectively (report reviewed before sign out) or retrospectively (report reviewed after sign out). Prospective reviews are more likely to be performed on criminal or criminally suspicious cases, pediatric and SIDS deaths and high profile cases. Retrospective reviews on the other hand are performed on a proportion of all other signed-out routine medico-legal cases. The actual percentage varies by jurisdiction since there are no agreed minimum standards. Manpower and workload factors appear to be critical to determining what percentage of cases are reviewed retrospectively. The objective of this report is to present a mechanism by which a 100% retrospective review policy has been implemented, how it integrates with quality management protocols, the outcomes of the reviews and what challenges remain to improve compliance with key quality indicators especially turn around time (TAT) statistics. PMID- 24237822 TI - Pilot study on doctors working in departments of forensic medicine in German speaking areas. AB - Several directors of institutes of forensic and legal medicine in German-speaking areas have noticed a lack of young doctors with specialty qualifications (full board certification) in forensic medicine during recent years. The pilot study was intended to brainstorm the possible reasons for this shortage, by carrying out a survey of doctors working in departments of forensic medicine, paying particular attention to job satisfaction and opinions as to why there are fewer forensic specialists. We sent the link to an online questionnaire to all members of the societies of forensic medicine in Germany, Switzerland and Austria. Altogether, 129 respondents completed the questionnaire and were included in the study. Slightly more men than women replied; the mean age of all respondents was 41. Most respondents had completed their specialty training and worked full-time. In general, participants were moderately satisfied with their careers. Men reported greater career success than women, as determined by objective criteria. Career support was considered to be suboptimal. For most of the respondents, the level of enjoyment of working in forensic medicine was either higher than or approximately the same as the level recalled from five years earlier. Possible reasons for the lack of qualified doctors in forensic medicine institutes are the non-availability of both senior posts and specialty training posts. Career opportunities in forensic medicine are not considered to be attractive. PMID- 24237823 TI - Estimation of postmortem time based on aorta narrowing in CT imaging. AB - Computed tomography (CT) in forensic medicine is commonly used in determination of cause of death. Here, we show that the information provided by CT may also be of value for estimation of time after death. The relationship between abdominal aorta narrowing just below the diaphragm and time after death was examined in 140 cases. Aorta narrowing was defined using a flatness ratio, which was calculated by dividing the shorter axis of the aorta by the longer axis. Time after death was classified into 6 time periods. The flatness ratio gradually and significantly decreased with increased postmortem time, showing increased aorta narrowing with increased time after death. A further examination of aorta narrowing in 15 autopsy cases in which CT images were taken at two postmortem times gave similar findings. The results of the study suggest that aorta narrowing in postmortem CT imaging may be used to estimate time after death. PMID- 24237824 TI - Survey of factors related to criminal behavior in a sample of Iranian substance abusers. AB - OBJECTIVES: Many countries including Iran have a high rate of substance abuse. It is essential for public health and law enforcement strategies to know the causes and consequences of substance abuse and its relation to crimes. METHODS: In a prospective case-control study, covering a period of one year starting from March 21, 2010, 125 cases with criminal behavior and 125 cases with no history of criminal behavior were studied. RESULTS: Eight percent of our studied population had a previous history of psychological disorder. Most of our cases were cigarette users (78.4%). Forty-two cases had a history of alcohol abuse (16.8%). Modern drugs were the most common type of drugs (56%) being used. Multivariate analysis using logistic regression revealed that criminal behavior was correlated with divorce (RR = 5.35; 95% CI = 1.59-16.01; P = 0.023), history of alcohol use (RR = 2.63; 95% CI = 1.11-6.22; P = 0.027), history of psychological disorder (RR = 4.97; 95% CI = 1.44-17.20; P = 0.011), Modern drug use (RR = 4.86; 95% CI = 2.01-11.76; P = 0.001) and starting drug abuse at an early age (RR = 0.94; 95% CI = 0.88-0.99; P = 0.03). CONCLUSIONS: Risk factors for criminal behavior among substance abusers include being divorced, history of alcohol abuse, history of psychological disorder, modern drug abuse and starting drug abuse at an early age. PMID- 24237825 TI - Electrocardiographic changes in attempted-hanging. PMID- 24237826 TI - Medical, social, and law characteristics of intoxicant's users medically examined in police custody. AB - INTRODUCTION: There are no studies on medically examined persons in custody which specifically focus on identifying dependence profiles among users of intoxicants. Nonetheless, the characterisation of dependence profiles for intoxicants such as alcohol, cannabis, cocaine, heroin, amphetamines and their by-products is a medical necessity in this setting. MATERIALS AND METHODS: A prospective, monocentric, open-ended study conducted by structured questionnaire was carried out on detainees who admitted to having taken an intoxicant/s (tobacco, alcohol, drugs or illegal substances). Social, legal and medical data were collected. The aim of the study was to explore characteristics of these persons in police custody. RESULTS: 817 questionnaires were examined. More than one-third have a dependence on at least one substance. 37.7% were dependant of tobacco, 86.5% of drinkers, 24.7% of cannabis users. Of these, 90.1% were from men with a mean age of 29.4 years, 40% from individuals living alone, 25.7% from persons with no financial means and 19.6% from homeless persons. 10% were believed to be suffering from mental illness, 7.2% were thought to be asthmatic, 3% to have a chronic infection, and 2.9% to have epilepsy. 36.2% reportedly received treatment, 37.5% of which included benzodiazepine and 20.3% opiate substitution therapy. Incidence of psychological and psychiatric disorders is close to 10% of intoxicant detainees. DISCUSSION: In this study, some of the stated pathologies occur in ratios similar to those in other published results. But, there is a high, and probably underestimated, prevalence of psychological and psychiatric disorders in this population of detainees reporting exposure to intoxicant or illegal substances. PMID- 24237827 TI - Patterns of infant mortality in Kuwait from 2003 to 2006. AB - Infant death is often tragic, particularly in the Arab World, where infants, especially males, are supposed to carry their family's names due to ancient cultural traditions. The conditions and events that may be associated with infant death are extremely varied. Infants may die from either congenital disorders or natural diseases, or may pass away as a consequence of a complicated delivery. Infants are also victims of accidents and violence such as homicides. The main aim of this study was to investigate the reported medico legal cases of infant mortality in Kuwait due to natural and un-natural causes between 2003 and 2006. The average IMR rate in Kuwait during the study period was better than the IMR average for developing countries and the IMR average for the world during the same study period. In general, these figures for Kuwait are even better than the average for Middle East and North Africa. More medico- legal cases were reported for deaths among Kuwaiti infants in 2004, 2005 and 2006 compared to non Kuwaiti infants. More Kuwaiti infants died due to RTA and domestic accidents. In contrast, only non Kuwaiti infant died from infanticide. PMID- 24237828 TI - Forensic and population genetic analyses of eighteen non-CODIS miniSTR loci in the Korean population. AB - We analyzed the variation of eighteen miniSTR loci in 411 randomly chosen individuals from Korea to increase the probability that a degraded sample can be typed, as well as to provide an expanded and reliable population database. Six multiplex PCR systems were developed (multiplex I: D1S1677, D2S441 and D4S2364; multiplex II: D10S1248, D14S1434 and D22S1045; multiplex III: D12S391, D16S3253 and D20S161; multiplex IV: D3S4529, D8S1115 and D18S853; multiplex V: D6S1017, D11S4463 and D17S1301; multiplex VI: D5S2500, D9S1122 and D21S1437). Allele frequencies and forensic parameters were calculated to evaluate the suitability and robustness of these non-CODIS miniSTR systems. No significant deviation from Hardy-Weinberg equilibrium expectations were observed, except for D4S2364, D5S2500 and D20S161 loci. A multidimensional scaling plot based on allele frequencies of the six miniSTR loci (D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045) showed that Koreans appeared to have most genetic affinity with Chinese and Japanese than to other Eurasian populations compared here. The combined probability of match calculated from the 18 miniSTR loci was 2.902 * 10( 17), indicating a high degree of polymorphism. Thus, the 18 miniSTR loci can be suitable for recovering useful information for analyzing degraded forensic casework samples and for adding supplementary genetic information for a variety of analyses involving closely related individuals where there is a need for additional genetic information. PMID- 24237829 TI - Uncertain testamentary capacity. AB - This letter illustrates the significance of the legal rules that resolve uncertainty in assessments of testamentary capacity. PMID- 24237830 TI - Fatal intimate partner violence against women in Portugal: a forensic medical national study. AB - Intimate partner violence (IPV) is an important cause of women's health and socio familial severe problems, the most extreme being the victims' homicide. This is the first nationwide Portuguese autopsy-based and judicial-proven study about female intimate partner homicide. At least 62 women over 15 years old were killed by current or former men-intimate partners, corresponding to an IPV-related female mortality rate of 0.44/100.000 women; intimate partner violence was the reason of homicide in 60.8% of all autopsied women. The typical Portuguese victim showed to be a young adult woman, employed, killed by a current husband in a long term relationship, usually with children in common and with a history of previous IPV. The typical Portuguese perpetrator showed to be older than the victim, employed, owning a firearm and without criminal records. At the time of the fatal event 59.7% of the relationships were current. In 57.9% of the former relationships women were killed during the 1st year after its terminus. Near half of the perpetrators attempted or committed suicide afterward. Most women were killed by gunshot wounds (45.2%), especially in the thorax (48.4%), with multiple fatal injuries; 56.5% also presented non-fatal injuries. The detection of prior IPV and the risk evaluation seems to be fundamental to decrease these fatal outcomes, but also, the prevention of perpetrators' alcohol abuse and carrying weapons. This work emphasizes the need to deepen the research on this issue, aiming to contribute to prevent both fatal and non-fatal IPV-related cases. PMID- 24237831 TI - Assessment of knowledge about, attitudes toward, and awareness of a forensic medicine course among medical students at the University of Dammam. AB - AIM: This study assesses the knowledge about, awareness of, and attitudes toward forensic medicine and the forensic medicine undergraduate course among medical students at the University of Dammam in Dammam, Saudi Arabia. METHOD: We conducted a cross-sectional study of 143 fourth-year students. We used a structured, self-administered questionnaire containing 10 items relating to forensic medicine to assess the knowledge about, awareness of, and attitudes toward forensic medicine and the forensic medicine undergraduate course. RESULTS: The results showed inadequate knowledge about, poor attitudes toward, and limited awareness of the importance of the forensic medicine course among medical students. Media had an effect on the students as they are a major source of forensic science information among medical students. CONCLUSION: The forensic medicine undergraduate course is important for medical students. We recommended that it be taught at the undergraduate level because it is the only academic source for forensic medicine that physicians may encounter in their careers. Teaching how to conduct an autopsy is important and has a positive role in medical education, and the forensic medicine curriculum must include instruction on autopsies, both from theoretical and practical perspectives. Medical institutes must take responsibility to increase awareness about the effect of media on medical education. PMID- 24237832 TI - Post-burning fragmentation of calcined bone: implications for remains recovery from fatal fire scenes. AB - This research assesses how short term delays in time-until-recovery can affect the quality and quantity of burnt bone recovered from a fatal fire scene. Knowledge of trends in post-burning remains fragmentation will enable investigators to prioritise remains recovery and implement recovery protocols appropriately. By comparing calcined bone fragments recovered 0, 24, 56 and 168 h (1 week) after experimental burns, this research describes remains fragmentation over time. Sus scrofa (domestic pig) limbs were burnt in a series of wood fuelled fires with calcined remains recovered at the specified time intervals. Bone fragments were sorted into 12 size based categories and the proportional weight of each category compared to observe differences in fragmentation over time. Results reveal marked increases in fragmentation when recovery is delayed by 24 h but less change in fragmentation between 24 and 56 h delay when breakage is reduced in the larger fragments. Between 56 and 168 h delay large increases in fragmentation occurred across all fragment sizes. These results indicate that short term recovery delays (24 h) can be detrimental to remains condition, but if remains recovery cannot be completed soon after the fire intermediate delays (56 h) are less significant. Longer term delays (168 h) are again potentially highly detrimental. PMID- 24237833 TI - Suicidal hanging in Kuwait: retrospective analysis of cases from 2010 to 2012. AB - Suicide is an important health hazard worldwide. We retrospectively analyzed the autopsy records of the Institute of Forensic Medicine between 2010 and 2012 to document the characteristics of fatalities resulting from hanging in Kuwait. Upon analysis of death scene investigation and autopsy reports together with the information gathered from the police, the cases of hanging fatalities of suicidal origin were selected. A retrospective study was carried out on 118 suicidal hanging cases autopsied at Forensic Medicine Center in Kuwait (from 2010 to 2012). Of these cases, 86 (73%) were males and 32 females (27%). There was an increasing trend of hanging among ages between 21 and 50 years (87.3%) and the third decade had the highest number of victims (about 43%) between all age groups. Local Kuwaiti nationals comprised a small proportion of cases (7 persons, 5.9%), while the others were foreigners working in Kuwait with an Indian precedence (54 persons, 54.8%), followed by other 12 different nationalities representing 39.3% of the cases. In conclusion, there was a decreasing trend of suicide by hanging in Kuwait from 44 cases in 2010 to 25 cases in 2012. PMID- 24237834 TI - Toxicology, circumstances and pathology of deaths from acute alcohol toxicity. AB - Alcohol consumption makes a large contribution to premature mortality. In order to extend our understanding of the characteristics, circumstances, toxicology and pathology of alcohol toxicity deaths, all cases presenting to the Department of Forensic Medicine Sydney between 1/1/1997-31/12/2011 with blood alcohol concentrations (BACs) >=0.300 g/100 ml and where the direct cause of death was acute alcohol toxicity were retrieved (n = 83). The mean age was 47.2 yrs and 77.1% were male. The majority (81.9%) of deaths occurred in a home environment, and did not vary across month or day of the week. In 91.6% of cases, a history of alcoholism or heavy alcohol consumption was reported. None were in any form of substance dependence treatment at the time of death. The mean BAC was 0.420 g/100 ml (range 0.300-0.741 g/100 ml). In 33.7% of cases, other substances were detected, predominantly diazepam (28.9%). BACs did not vary significantly by gender, age or BMI. Urine/BAC ratios of >1.25 were seen in 6/43 cases where both samples were available. Cardiac disease was noted in 75.9% of cases and hepatic disease in 91.6%. The only alcohol-related organic brain syndrome pathology identified at autopsy was vermal cerebellar degeneration. PMID- 24237835 TI - A comparison of ABAcard((r)) p30 and RSIDTM-Semen test kits for forensic semen identification. AB - The screening and confirmatory tests available to a forensic laboratory allow evidence to be examined for the presence of bodily fluids. With the majority of evidence being submitted involving sexual assaults, it is important to have confirmatory tests for the identification of semen that are straightforward, quick, and reliable. The purpose of this study was to compare two commonly used semen identification kits utilized by forensic laboratories: ABAcard((r)) p30 and Rapid Stain Identification of Human Semen (RSIDTM-Semen). These kits were assessed with aged semen stains, fresh and frozen post-vasectomy semen, post coital samples collected on different substrates, post-vasectomy semen mixed with blood, saliva, and urine, a series of swabs collected at increasing time intervals after sexual intercourse, and multiple non-semen samples. The test kits were compared on the basis of sensitivity, specificity, and the cost and time effectiveness of each protocol. Overall, both semen identification tests performed well in the studies. Both kits proved specificity for identifying semen, however the ABAcard((r)) p30 test surpassed the RSIDTM-Semen test in sensitivity, cost per test, and simplified test protocol. PMID- 24237836 TI - Adverse event analysis in fatal cases of influenza A (H1N1) - a lesson from Poland. AB - During pandemic of influenza A (H1N1) in 2009 the relationship between mortality and medical errors, especially delayed antiviral treatment initiation, was highlighted in many studies. Our study was based on 5 fatal cases of pandemic influenza A (H1N1) hospitalized in Poland between November 2009 and February 2011. The material included data from medical documentation as well as testimonies from medical personnel and patients' families recorded during on going lawsuits alleging medical malpractice. The risk factors of adverse events were: lack of typical symptoms, lack of detailed medical history, clinical masking of a "trivial" illness, doctors' ignorance and insufficient knowledge, several physicians treating the same patient during hospitalization. Recommendations for improving management of pandemic infectious disease include: an effective, quick and detailed system of information about the epidemiological threat, clear indication of units with diagnostic and medical possibilities, rational health policy and national system of closed claims and adverse event analysis. PMID- 24237837 TI - Difficulties in personal identification caused by unreliable dental records. AB - This paper demonstrates a case of personal identification that initially seemed straightforward, mainly because complete and comprehensive antemortem dental records of a missing person were made available for analysis. Skeletal remains were found and the skull (most crucial for human identification) was delivered for analysis. Comparative analysis of antemortem and postmortem dental records excluded identification, while the results of superimposition (simultaneously performed by another team member) revealed sufficient concordant points to establish identity. The results caused confusion and additional information was required. The need for more evidence resulted in delivery of elements of the postcranial skeleton. Identification was finally achieved when concordant points were established in a comparison of antemortem X-rays and the humerus. Team members concluded that the dental records were in fact not adequate and that mistakes in numbering the teeth (superior canine instead inferior canine and right and left premolars) were considered to be the initial reason a positive identification had not been made. The authors conclude that a multidisciplinary approach is crucial to making a positive identification and that caution should be exercised when carrying out personal identification from dental records alone. The need to adequately train police officers to collect and preserve dental evidence is also emphasized. PMID- 24237838 TI - Fatal crocodile attack. AB - Attacks on human beings by various animals leading to varied types of injuries and even death in some cases are not uncommon. Crocodile attacks on humans have been reported from a number of countries across the globe. Deaths in such attacks are mostly due to mechanical injuries or drowning. Bites by the crocodiles often cause the limbs to be separated from the body. The present case refers to an incident of a fatal attack by a crocodile on a 35 years old female where only the mutilated head of the female was recovered. Multiple lacerated wounds over the face and scalp along with fracture of the cranial bones was detected on autopsy. Two distinct bite marks in the form of punched in holes were noted over the parietal and frontal bones. Injuries on the head with its traumatic amputation from the body were sufficient to cause death. However, the presence of other fatal injuries on the unrecovered body parts could not be ruled out. PMID- 24237839 TI - The assessment of lens opacity postmortem and its implication in forensics. AB - Visual impairment, mostly due to cataracts, has been demonstrated to be an important factor associated with traffic accidents. Although vision screening is standard procedure during licensing in order to prevent motor vehicle accidents, an eye exam is not typically administered after an accident has already occurred. Postmortem assessment of lens opacity in victims of car accidents would provide helpful information for attesting to the liability of the parties in specific accidents, determining the circumstances of the accident, and developing preventive measures for both drivers and pedestrians alike. In this paper, we explore the use of different methods and their limitations for assessing lens opacity postmortem. We discuss the possible use and benefits of a simple, but as yet untested method: retrobulbar translucency. The method would be based on the recording of shadows formed by opaque regions of the lens while the eye is illuminated from the back with a rigid source of light. The efficacy and objectivity of the method, its reproducibility, and the inter- and intra-observer error should be tested before implementing such a technique to be regularly used to determine lens opacity in cadavers. PMID- 24237840 TI - Patterned genital injury in cases of sexual assault. PMID- 24237841 TI - Answer to the comments made by Prof Chariot to our original paper 'patterned genital injury in cases of rape - a case-control study'. PMID- 24237842 TI - A single case report lacking details does not equal a mimic of abusive head trauma. PMID- 24237843 TI - Significance of descriptive statistics in forensic anthropology research. PMID- 24237844 TI - Aluminum & cardiac arrhythmias; occupational medicine aspect of a case report. PMID- 24237845 TI - Mobitz type II second-degree atrioventricular block with narrow QRS and junctional extrasystoles: what is the mechanism? AB - A 74-year-old man underwent an electrophysiological study because of Mobitz type II second-degree atrioventricular (AV) block with narrow QRS and frequent junctional extrasystoles. During the study, there were very frequent single His bundle depolarizations with multiple coupling intervals that reproduce the ECG findings. In this case, some His bundle extrasystoles result in retrograde concealed conduction and prolonged local refractoriness in the AV node that manifest as block of the next atrial impulse. PMID- 24237846 TI - An investigation of economic costs of schizophrenia in two areas of China. AB - BACKGROUND: Schizophrenia is a severe psychotic disorder characterized by significant disturbances in thinking, perception, emotions and behavior. Even if it is not a very frequent disorder, but it is the most burdensome and costly illnesses worldwide. The total population was approximate 1.3 billion and there are approximate 8 million schizophrenic patients in China. Despite the wide ranging financial and social burdens associated with schizophrenia, but there have been few cost-of-illness studies of this illness in China. OBJECTIVE: To evaluate the economic cost of schizophrenic patients in China. METHODOLOGY: 356 schizophrenic patients who met with DSM-IV criteria were enrolled and investigated with the Economic Burden Questionnaire(EBQ), 299 schizophrenic patients completed the study for 12 months. All the data were combined and classified by researcher. EBQ include all kinds of cost such as direct cost, indirect cost and total cost as well. It was filled in by patients and their close caregivers. Comparison of cost was made between not only out-patients and in-patients but also urban patients and rural patients. Multiple stepwise regression analysis was made to identify the main influence factors of total cost. RESULTS: (i) The per case per annum total costs, direct costs and indirect costs of schizophrenia amounted to US$2586.21, US$862.81(33.4%) and US$1723.40(66.6%) respectively. The per case total cost, direct cost and direct medical cost of in-patients were more higher than out-patients (P < 0.05). (ii) There was significant difference in per case per annum total cost, direct cost, direct medical cost, cost due to lost working-days and disability between urban and rural schizophrenic patients (P < 0.05), the former is higher than the latter. (iii) The results of multivariate stepwise regression analysis show that five variables were significantly correlated with higher cost: professional status(cadre), diagnostic subtype(residual schizophrenia), urban or rural patients(urban patients), in-patients or out-patients(in-patients) and researcher centre(southern center). The standardized regression coefficient were 0.308, 0.218, 0.212, 0.156 and 0.149 respectively, the correlation of determination R square was 0.2741, F = 15.651, P < 0.0000. These characteristics explain 27.41% of the variability in the total cost. CONCLUSION: (i) Economic cost of schizophrenia were serious, we must pay close attention to it. (ii) The indirect cost are the majority of the total cost. The cost of urban patients are more higher than the cost of rural patients, the cost of in-patients are more higher than the cost of out-patients. PMID- 24237847 TI - Perioperative outcomes in patients with rheumatoid versus osteoarthritis for total hip arthroplasty: a population-based study. AB - OBJECTIVES: Little is known about perioperative outcomes among the subset of patients undergoing total hip arthroplasty (THA) for a diagnosis of rheumatoid arthritis (RA) rather than osteoarthritis (OA). We sought to 1) identify the prevalence of RA in patients undergoing THA, 2) compare their demographics to those being operated on for OA, 3) determine differences in perioperative outcomes and 4) analyse if RA represents an independent risk factor for complications, mortality, utilisation of resources, increased length of stay and cost. METHODS: Entries of patients who underwent elective THA between 2006 and 2010 were identified in a national database and subgrouped according to presence of a concurrent diagnosis of RA. Differences in demographics and perioperative outcomes were analysed. RESULTS: We identified 157,775 entries for patients who underwent THA between 2006 and 2010. RA was present in 3.42% (n=5,400). Patients in the group RA were on average younger [RA: 63.94 years vs. OA: 65.64 years; p<0.0001] and more likely female [RA: 75.47% vs. OA: 56.09%; p<0.0001]. While mortality was not statistically different, perioperative pulmonary and infectious complications occurred more frequently in RA patients. Compared with OA, multivariate logistic regression revealed higher overall odds for complications [OR=1.15 (CI 1.05;1.25), p=0.0037], need for mechanical ventilation [OR=1.42 (CI 1.01;2.00), p=0.0414], transfusion [OR=1.35 (CI 1.26;1.44), p<0.0001], prolonged hospitalisation [OR=1.16 (CI 1.08;1.23), p<0.0001] and increased hospital charges [OR=1.17 (CI 1.09;1.26), p<0.0001]. CONCLUSIONS: In THA patients suffering from RA, perioperative risk for complications and utilization of health care resources continues to be increased compared to OA patients. PMID- 24237848 TI - Evaluating the impact of depression, anxiety & autonomic function on health related quality of life, vocational functioning and health care utilisation in acute coronary syndrome patients: the ADVENT study protocol. AB - BACKGROUND: Depression and anxiety are highly prevalent and co-morbid in acute coronary syndrome patients. Somatic and cognitive subtypes of depression and anxiety in acute coronary syndrome have been shown to be associated with mortality although their association with patient outcomes is unknown, as are the mechanisms that underpin these associations. We are conducting a prospective cohort study which aims to examine in acute coronary syndrome patients: (1) the role of somatic subtypes of depression and anxiety as predictors of health related quality of life outcomes; (2) how somatic subtypes of depression and anxiety relate to long term vocational functioning and healthcare utilisation; and (3) the role of the autonomic nervous system assessed by heart rate variability as a moderator of these associations. METHODS: Patients are being screened after index admission for acute coronary syndrome at a single, high volume centre, MonashHeart, Monash Health, Victoria, Australia. The inclusion criterion is all patients aged > 21 years old and fluent in English admitted to MonashHeart, Monash Health with a diagnosis of acute coronary syndrome. The primary outcome is mean health related quality of life (Short Form-36) Physical and Mental Health Summary scores at 12 and 24 months in subtypes with somatic symptoms of depression and anxiety. Depressive domains are assessed by the Beck Depression Inventory II and the Cardiac Depression Scale. Anxiety is measured using the Speilberger State-Trait Anxiety Inventory and the Crown Crisp Phobic Anxiety questionnaire. Secondary outcomes include clinical variables, healthcare service utilisation and vocational functioning. DISCUSSION: This manuscript presents the protocol for a prospective cohort study which will investigate the role of somatic subtypes of depression and anxiety as predictors of health related quality of life, long-term vocational functioning and health service use, and the role of the autonomic nervous system in moderating these associations. Findings from the study have the potential to inform more effective pharmacological, psychological and behavioural interventions and better guide health policy on the use of health care resources. PMID- 24237849 TI - Proteomic characterization of serine hydrolase activity and composition in normal urine. AB - BACKGROUND: Serine hydrolases constitute a large enzyme family involved in a diversity of proteolytic and metabolic processes which are essential for many aspects of normal physiology. The roles of serine hydrolases in renal function are largely unknown and monitoring their activity may provide important insights into renal physiology. The goal of this study was to profile urinary serine hydrolases with activity-based protein profiling (ABPP) and to perform an in depth compositional analysis. METHODS: Eighteen healthy individuals provided random, mid-stream urine samples. ABPP was performed by reacting urines (n = 18) with a rhodamine-tagged fluorophosphonate probe and visualizing on SDS-PAGE. Active serine hydrolases were isolated with affinity purification and identified on MS-MS. Enzyme activity was confirmed with substrate specific assays. A complementary 2D LC/MS-MS analysis was performed to evaluate the composition of serine hydrolases in urine. RESULTS: Enzyme activity was closely, but not exclusively, correlated with protein quantity. Affinity purification and MS/MS identified 13 active serine hydrolases. The epithelial sodium channel (ENaC) and calcium channel (TRPV5) regulators, tissue kallikrein and plasmin were identified in active forms, suggesting a potential role in regulating sodium and calcium reabsorption in a healthy human model. Complement C1r subcomponent-like protein, mannan binding lectin serine protease 2 and myeloblastin (proteinase 3) were also identified in active forms. The in-depth compositional analysis identified 62 serine hydrolases in urine independent of activity state. CONCLUSIONS: This study identified luminal regulators of electrolyte homeostasis in an active state in the urine, which suggests tissue kallikrein and plasmin may be functionally relevant in healthy individuals. Additional serine hydrolases were identified in an active form that may contribute to regulating innate immunity of the urinary tract. Finally, the optimized ABPP technique in urine demonstrates its feasibility, reproducibility and potential applicability to profiling urinary enzyme activity in different renal physiological and pathophysiological conditions. PMID- 24237851 TI - Quality of life in non-melanoma skin cancer--the skin cancer quality of life (SCQoL) questionnaire. AB - BACKGROUND: Disease-specific quality of life (QoL) questionnaires are increasingly used to provide patient-reported out-come measures in both malignant and non-malignant disease. OBJECTIVE: To create, validate and test the psychometrics of the Skin Cancer Quality of Life (SCQoL), which was designed to measure health-related QoL in patients with non-melanoma skin cancer affecting any area and undergoing any therapy. METHODS AND MATERIALS: The SCQoL was developed in a stepwise approach. Three pilot studies (testing content and face validity) and psychometric testing (scale structure, reliability, domains and known-groups validity, concurrent and convergent validity) were conducted. Rasch analyses were performed on the final questionnaire. RESULTS: The initial 10-item questionnaire was reduced to 9 items following interviews and inter-item correlations. The nine item scale was confirmed by Item Response Theory (IRT) and internal consistency. Differential Item Functioning (DIF) was found for a single item, but the effect was small. CONCLUSION: The final 9-item SCQoL is unidimensional and consists of 3 domains covering function, emotions and control. Furthermore there is one single global item. The total score range from 0 to 27. Higher score denote a greater impairment of the QoL. PMID- 24237850 TI - Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two-month open label pilot study. AB - BACKGROUND: Malnutrition is a widespread problem in elderly people and is associated with cognitive decline. However, interventional studies have produced ambiguous results. For this reason, we wanted to determine the effect of micronutrient supplementation on blood and tissue levels and on general nutritional status in persons with mild or moderate cognitive impairment. METHODS: We performed a 2-month, open-label trial, administering a daily micronutrient supplement to 42 memory clinic patients with mild cognitive deficits. Blood levels of antioxidants, zinc, and B vitamins were determined before and after supplementation. In addition, we assessed metabolic markers for B vitamins and intracellular (buccal mucosa cell [BMC]) antioxidant levels. Nutritional status was assessed by using the Mini Nutritional Assessment (MNA). RESULTS: Blood levels of B vitamins, folic acid, lutein, beta-carotene, alpha carotene, and alpha-tocopherol increased significantly. Decreases in homocysteine levels and the thiamine pyrophosphate effect and an increase in holotranscobalamin were observed. We found no increase in intracellular antioxidant levels of BMC. The MNA score in subjects at risk for malnutrition increased significantly, mainly owing to better perception of nutritional and overall health status. CONCLUSIONS: Micronutrient supplementation improved serum micronutrient status, with improved metabolic markers for B vitamins but not for intracellular antioxidant status, and was associated with improved self perception of general health status. Our data underline the necessity of determining micronutrient status and support the use of additional assessments for general health and quality of life in nutritional supplementation trials. PMID- 24237852 TI - [Results or pelvi-perineal rehabilitation in patients with pelvic floor dyssynergia]. AB - INTRODUCTION: Pelvic floor dyssynergia (PPD) is a common cause of outlet obstruction constipation. Treatment for this condition is based on pelvi-perineal re-education (PPR). The aim of this study was to evaluate the results of PPR on patients with PPD METHODS: Patients with the diagnosis of PPD were included. The study was conducted between 2010 and 2011. PPR was performed by specialized kinesiologists. Prior and after treatment a constipation questionnaire was performed (KESS) (scale from 0 to 39 points, a higher score is associated with more symptom severity). KESS score before and after PPR were compared. Mann Whitney-Wilcoxon rank sum test for paired samples was used for statistical analysis, p value <0,05 was considered as significant. RESULTS: Thirteen patients were included (11 women), mean age 44.3 years old (r: 18-76). Mean total KESS score prior and after PPR were 19.6 (SD: 5.8) and 12.6 (DS: 63), respectively (P=.002). Frequency of bowel movements, stool consistency, abdominal pain and abdominal bloating did not present statistically significant changes before and after treatment. Use of laxatives, enemas and/or digitations, as well as unsuccessful evacuation, feelings of incomplete evacuation improved significantly. Total evacuation time (before 1.53 vs after 1; P=.012) and difficult evacuation causing painful efforts (before 2.08 vs after 1.07; P=.001) also decreased significantly. CONCLUSION: PPR in patients with PPD, significantly improves the symptoms of obstructive constipation, mainly with respect to mechanical assistance and difficult evacuation. PMID- 24237853 TI - Choosing surgery as a specialty: opinions of medical students about surgery and surgeons. AB - INTRODUCTION: Since the number of applicants to residencies in general surgery in Argentina seems to be decreasing, we designed this work with the objective of studying the factors considered undesirable by students when choosing surgery as a specialty. MATERIAL AND METHODS: Between March and April 2012, one-hundred students were surveyed with a structured questionnaire with true/false binary answers in an observational case-control design. The survey contained 26 statements that made reference to characteristics of surgery as a specialty, or about the personality and lifestyle of surgeons, as they could be perceived by students. As a control group the same survey was applied to 20 surgeons who were in contact with the students and that could represent a role model for them during their rotation in surgery. RESULTS: Comparison between students and surgeons showed no difference in most answers, except in "surgery has poor reimbursement" (OR: 8,9; P=.0001), "there is not enough job demand" (OR: 8,1; P=.015), "surgery restrains intellectual development" (OR: 17,5; P=.014), "surgeons have too many non-scheduled activities" (OR: 9,36; P=.024), "they have a limited patient-physician relationship" (OR: 3,61; P=.009), "they have little time for family" (OR: 4,27; P=.036) and "they are exposed to infectious diseases" (OR: 5,90; P=.007). CONCLUSIONS: Women would be as interested as men in working as surgeons; a remarkable fact when considering that the surgical specialties have been predominantly filled by men. The fact that surgeons mostly coincide with the views of students means that role models should be reviewed to promote vocations. PMID- 24237855 TI - Insomnia and accidents: cross-sectional study (EQUINOX) on sleep-related home, work and car accidents in 5293 subjects with insomnia from 10 countries. AB - The link between sleepiness and the risk of motor vehicle accidents is well known, but little is understood regarding the risk of home, work and car accidents of subjects with insomnia. An international cross-sectional survey was conducted across 10 countries in a population of subjects with sleep disturbances. Primary care physicians administered a questionnaire that included assessment of sociodemographic characteristics, sleep disturbance and accidents (motor vehicle, work and home) related to sleep problems to each subject. Insomnia was defined using the International Classification of Sleep Disorders (ICSD-10) criteria. A total of 5293 subjects were included in the study, of whom 20.9% reported having had at least one home accident within the past 12 months, 10.1% at least one work accident, 9% reported having fallen asleep while driving at least once and 4.1% reported having had at least one car accident related to their sleepiness. All types of accident were reported more commonly by subjects living in urban compared to other residential areas. Car accidents were reported more commonly by employed subjects, whereas home injuries were reported more frequently by the unemployed. Car accidents were reported more frequently by males than by females, whereas home accidents were reported more commonly by females. Patients with insomnia have high rates of home accidents, car accidents and work accidents related to sleep disturbances independently of any adverse effects of hypnotic treatments. Reduced total sleep time may be one factor explaining the high risk of accidents in individuals who complain of insomnia. PMID- 24237854 TI - Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle. AB - BACKGROUND: Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE4) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations. METHODS: In the present study we investigated whether the PDE4 inhibitor piclamilast (10(-6) M) could alter RV or viral mimetic (5 MUg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E2 and cAMP production were assayed by ELISA and RV replication was assayed by viral titration. RESULTS: We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL 6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines. CONCLUSION: By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE4 inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV. PMID- 24237856 TI - Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. AB - Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR's threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource. PMID- 24237857 TI - Distal intestinal obstruction syndrome in cystic fibrosis: presentation, outcome and management in a tertiary hospital (2007-2012). AB - BACKGROUND: Cystic fibrosis (CF) can result in distal intestinal obstruction syndrome (DIOS) due to inspissated mucus. This paper describes the clinicopathological characteristics of adult CF patients with DIOS and assesses risk factors for surgery. METHODS: A retrospective audit of CF patients at the Alfred Hospital from January 2007 to February 2012 was carried out. Patients who had 'bowel obstruction or constipation' were abstracted from the database, and medical records were reviewed for a diagnosis of DIOS. RESULTS: Forty-five encounters of 35 patients were extracted. Twenty-five (83%) patients were homozygous for the delta F508 mutations, 29 (85%) had pancreatic insufficiency and 15 (44%) had a lung transplant. Patients presented with abdominal pain (96% of encounters), nausea (76% of encounters) and vomiting (67% of encounters). Computed tomography (CT) was performed in 20 episodes. Compared with CT, abdominal X-ray had a sensitivity of 63% (95% confidence interval (CI) 30-89%) and specificity of 33% (95% CI 8-70%) for detecting DIOS with obstruction. Forty one (91%) encounters resolved with medical management within 2-3 days. Three patients required surgical intervention in four episodes. Previous laparotomy (odds ratio (OR) 28.5, 95% CI 1.3-624, P=0.03) and history of meconium ileus (OR 14, 95% CI 1-192, P<0.05) were statistically significant predictors of progression to surgical management. CONCLUSION: In most patients with DIOS, the obstruction resolves with medical management. Early consultation with a CF service, assessment for a surgical abdomen and involvement of surgeons where appropriate is recommended. A history of previous laparotomy is a risk factor for the need for surgical intervention. PMID- 24237859 TI - Heart rate recovery: autonomic determinants, methods of assessment and association with mortality and cardiovascular diseases. AB - Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Cardiac autonomic dysfunction seems to be related to the genesis of several CVDs and is also linked to the increased risk of mortality in CVD patients. The quantification of heart rate decrement after exercise - known as heart rate recovery (HRR) - is a simple tool for assessing cardiac autonomic activity in healthy and CVD patients. Furthermore, since The Cleveland Clinic studies, HRR has also been used as a powerful index for predicting mortality. For these reasons, in recent years, the scientific community has been interested in proposing methods and protocols to investigate HRR and understand its underlying mechanisms. The aim of this review is to discuss current knowledge about HRR, including its potential primary and secondary physiological determinants, as well as its role in predicting mortality. Published data show that HRR can be modelled by an exponential curve, with a fast and a slow decay component. HRR may be influenced by population and exercise characteristics. The fast component mainly seems to be dictated by the cardiac parasympathetic reactivation, probably promoted by the deactivation of central command and mechanoreflex inputs immediately after exercise cessation. On the other hand, the slow phase of HRR may be determined by cardiac sympathetic withdrawal, possibly via the deactivation of metaboreflex and thermoregulatory mechanisms. All these pathways seem to be impaired in CVD, helping to explain the slower HRR in such patients and the increased rate of mortality in individuals who present a slower HRR. PMID- 24237858 TI - Cohort profile: risk evaluation of cancers in Chinese diabetic individuals: a longitudinal (REACTION) study. AB - OBJECTIVE: To demonstrate whether abnormal glucose metabolism (diabetes and prediabetes) is associated with increased risk for cancer in the Chinese population and to identify factors that modify the risk of cancer among individuals with abnormal glucose metabolism. METHODS: Between 2011 and 2012, 259 657 community-dwelling adults, aged 40 years and older, were recruited from 25 centers across mainland China to participant in the baseline survey of the REACTION study, with follow-up investigations performed 3, 5, and 10 years later. Detailed questionnaires about lifestyles, physical and biochemical measurement, bio-samples including serum, urine, and whole blood for DNA extraction were collected for all the participants. RESULTS: The mean +/- standard deviation (SD) age of this cohort was 57 +/- 10 years. And the prevalence of pre-existing and newly diagnosed diabetes was 10.32% and 10.57%, respectively. A total of 4511 prevalent cancer cases (988 men and 3523 women) were identified, the prevalence was 1.79. Compared to those with normal glucose metabolism, men with diabetes had a significantly lower adjusted prevalence ratio (PR) of stomach cancer (PR: 0.38, 95% CI: 0.16-0.89), and women with diabetes had significantly higher adjusted PRs of cancer of all sites (PR: 1.36, 95% CI: 1.20-1.56), and cancer of the breast (PR: 1.56, 95% CI: 1.21-2.00), the endometrium (PR: 1.58, 95% CI: 1.16-2.15), and the thyroid (PR: 1.53, 95% CI: 1.03-2.27). CONCLUSION: The multi-center REACTION study has captured a broad range of data on physical, psychological and metabolic function as well as health status, biochemical and lifestyle information in 259 657 adults from the general population across the China. PMID- 24237860 TI - Prevalence and clustering of soil-transmitted helminth infections in a tribal area in southern India. AB - OBJECTIVES: To estimate the prevalence, spatial patterns and clustering in the distribution of soil-transmitted helminth (STH) infections, and factors associated with hookworm infections in a tribal population in Tamil Nadu, India. METHODS: Cross-sectional study with one-stage cluster sampling of 22 clusters. Demographic and risk factor data and stool samples for microscopic ova/cysts examination were collected from 1237 participants. Geographical information systems mapping assessed spatial patterns of infection. RESULTS: The overall prevalence of STH was 39% (95% CI 36%-42%), with hookworm 38% (95% CI 35-41%) and Ascaris lumbricoides 1.5% (95% CI 0.8-2.2%). No Trichuris trichiura infection was detected. People involved in farming had higher odds of hookworm infection (1.68, 95% CI 1.31-2.17, P < 0.001). In the multiple logistic regression, adults (2.31, 95% CI 1.80-2.96, P < 0.001), people with pet cats (1.55, 95% CI 1.10-2.18, P = 0.011) and people who did not wash their hands with soap after defecation (1.84, 95% CI 1.27-2.67, P = 0.001) had higher odds of hookworm infection, but gender and poor usage of foot wear did not significantly increase risk. Cluster analysis, based on design effect calculation, did not show any clustering of cases among the study population; however, spatial scan statistic detected a significant cluster for hookworm infections in one village. CONCLUSION: Multiple approaches including health education, improving the existing sanitary practices and regular preventive chemotherapy are needed to control the burden of STH in similar endemic areas. PMID- 24237861 TI - Predictors for replanning in loco-regionally advanced nasopharyngeal carcinoma patients undergoing intensity-modulated radiation therapy: a prospective observational study. AB - BACKGROUND: Replanning in intensity-modulated radiotherapy (IMRT) has been reported to improve quality of life and loco-regional control in patients with nasopharyngeal cancer (NPC). Determination of the criteria for replanning is, however, urgently needed. We conducted a prospective study to determine when and for what type of patients is replanning preferred through weekly repeat computed tomography (CT) imaging during the course of IMRT. METHODS: We recruited 20 patients who were diagnosed as having loco-regionally advanced, non-metastatic stage III or IVa NPC and treated with concurrent platinum-based chemoradiotherapy (CRT) using IMRT. Patients received CT simulation (sim-CT) and plain magnetic resonance imaging (MRI) plus diffusion-weighted imaging (DWI) weekly for five consecutive weeks. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated and recorded weekly based on the CT-CT fusion. The relationship between GTV/CTV reduction and clinical characteristics of the patients were assessed using Pearson correlation test. RESULTS: GTV and CTV decreased during the treatment by 36.03 mL (range, 10.91-98.82 mL) and 76.79 mL (range, 33.94 125.14 mL), respectively, after 25 fractions of treatment. The percentage reductions from their initial volume were 38.4% (range, 25.3-50.7%) and 11.8% (range, 6.7-18.3%), respectively. The greatest reductions in GTV and CTV were observed at the fourth week (i.e., upon completion of 20 fractions), compared to pre-treatment sim-CT. Weight loss and CTV reduction were significantly correlated with pre-treatment body mass index (BMI ) (r =0.58, P =0.012, and r =0.48, P =0.046, respectively). However, no significant correlation was observed between CTV reduction and initial tumor volume. In addition, GTV reduction was not significantly correlated with pre-treatment tumor volume (P =0.65), but negatively correlated with pre-treatment tumor apparent diffusion coefficient (ADC) values (r = -0.46, P =0.042). CONCLUSIONS: Our results indicate that the most appropriate replanning time is after 20 fractions of treatment, and pre treatment BMI and ADC are potential predictive factors for the determination of replanning during IMRT. PMID- 24237863 TI - Birth prevalence for congenital limb defects in the northern Netherlands: a 30 year population-based study. AB - BACKGROUND: Reported birth prevalences of congenital limb defects (CLD) vary between countries: from 13/10,000 in Finland for the period 1964-1977 to 30.4/10,000 births in Scotland from 1964-1968. Epidemiological studies permit the timely detection of trends in CLD and of associations with other birth defects. The aim of this study is to describe the birth prevalence of CLD in the northern Netherlands. METHODS: In a population-based, epidemiological study we investigated the birth prevalences of CLD for 1981-2010. Data were collected by the European Surveillance of Congenital Anomalies in the northern Netherlands (EUROCAT-NNL). We excluded malpositions, club foot, and dislocation/dysplasia of hips or knees. Trends were analysed for the 19-year period 1992-2010 using chi2 tests, as well as CLD association with anomalies affecting other organs. RESULTS: The birth prevalence of CLD was 21.1/10,000 births for 1981-2010. There was an overall decrease in non-syndromic limb defects (P = 0.023) caused by a decrease in the prevalence of non-syndromic syndactyly (P < 0.01) in 1992-2010. Of 1,048 children with CLD, 55% were males, 57% had isolated defects, 13% had multiple congenital anomalies (MCA), and 30% had a recognised syndrome. The upper:lower limb ratio was 2:1, and the left:right side ratio was 1.2:1. Cardiovascular and urinary tract anomalies were common in combination with CLD (37% and 25% of cases with MCA). Digestive-tract anomalies were significantly associated with CLD (P = 0.016). CONCLUSIONS: The birth prevalence of CLD in the northern Netherlands was 21.1/10,000 births. The birth prevalence of non-syndromic syndactyly dropped from 5.2/10,000 to 1.1/10,000 in 1992-2010. PMID- 24237864 TI - The overall program effects of California's 3-Tier Assessment System pilot on crashes and mobility among senior drivers. AB - INTRODUCTION: In 2007, the California Department of Motor Vehicles (DMV) undertook a pilot study of the 3-Tier Assessment System, the purpose of which was to examine, in a large-scale real-time public agency setting, the effectiveness of this method for both reducing the crash risk of individual drivers and for extending the safe driving years of Californian drivers of all ages. METHOD: The 3-Tier Assessment System consisted of tiered series of screening tools incorporated into the in-office driver's license renewal process. These screening tools identified drivers with various kinds of functional limitations (physical, visual, and cognitive/perceptual), that might impact safe driving. Paired with the screening tools were educational materials designed to improve drivers' knowledge of their own limitations, including compensating techniques. The present study is a population-based evaluation of the effects of the pilot on subsequent crash risk and mobility outcomes (including delicensure) of participating drivers age 70 and older. Pilot participants were compared with two control groups processed according to standard California DMV license renewal procedures. Because the 3-Tier Assessment System was designed to identify limitations normally associated with aging, the present analyses focus on drivers age 70 and older. However, it should be emphasized that during the 3-Tier pilot the screening tools were applied to drivers of all ages. RESULTS: There were two main findings. First, there were no consistent, statistically significant differences between the pilot and control groups in crash risk in the two years following screening. Second, pilot participants experienced statistically significant effects on mobility. These effects included delays in time to complete their license renewal, an increase in the number of assigned license restrictions, and an increase in the number of customers failing to renew their driving privilege. CONCLUSIONS: Based on these findings, suggestions for further research are made. IMPACT ON INDUSTRY: None. PMID- 24237865 TI - Sustainability of community-based fall prevention programs: a systematic review. AB - BACKGROUND: Fall prevention programs may be implemented but not sustained. We conducted a systematic review to identify any theories, models, frameworks, influencing factors or interventions for sustaining fall prevention programs in the community. METHODS: Peer-reviewed publications describing, investigating, or evaluating program sustainability were accessed. A narrative review was conducted to compare and synthesize study findings. RESULTS: Nineteen publications were included. Three conceptual frameworks were identified describing how programs may be better sustained. While ongoing financial support and the participation of older people were commonly reported influences, other factors specific to the type of program and setting were also reported. Planning, training, and collaboration between program stakeholders may facilitate sustainable programs. IMPACT ON INDUSTRY: Organizations can use these findings when planning for sustainable programs. However more robust empirical studies are needed to confirm the value of conceptual frameworks, the critical factors and most effective interventions for sustaining community-based fall prevention programs. PMID- 24237862 TI - A systems biology view of blood vessel growth and remodelling. AB - Blood travels throughout the body in an extensive network of vessels - arteries, veins and capillaries. This vascular network is not static, but instead dynamically remodels in response to stimuli from cells in the nearby tissue. In particular, the smallest vessels - arterioles, venules and capillaries - can be extended, expanded or pruned, in response to exercise, ischaemic events, pharmacological interventions, or other physiological and pathophysiological events. In this review, we describe the multi-step morphogenic process of angiogenesis - the sprouting of new blood vessels - and the stability of vascular networks in vivo. In particular, we review the known interactions between endothelial cells and the various blood cells and plasma components they convey. We describe progress that has been made in applying computational modelling, quantitative biology and high-throughput experimentation to the angiogenesis process. PMID- 24237866 TI - Ambulatory cell phone injuries in the United States: an emerging national concern. AB - BACKGROUND: Over the past 15 years, the use of cell phones has increased 8-fold in the United States. Cell phone use has been shown to increase crash risks for drivers, but no systematic analyses have described injuries related to ambulatory cell phone use. OBJECTIVE: The purpose of this study is to describe and quantitate injuries and deaths among persons using cell phones while walking. METHODS: We searched the National Electronic Injury Surveillance System (NEISS) for emergency department (ED) reports of injuries related to phone use. The cases that returned were screened initially using words that would eliminate cases unlikely to be related to cell phone use and walking, possibly linked to distraction. The resulting cases were randomized and evaluated for consistency with predetermined case definitions by two authors blinded to the dates of the incidents. Cases that were disagreed upon were evaluated in a second screening by both authors for final case determination. National ED visit rates were estimated based on NEISS sampling methods. Annual variations were analyzed using linear regression with a restricted maximum likelihood approach. RESULTS: Our screening process identified 5,754 possible cases that occurred between 2000 and 2011, and 310 were agreed on as cases of cell-phone-induced distraction. The majority of the patients were female (68%) and 40 years of age or younger (54%). The primary mechanism of injury was a fall (72%), and most patients were treated and released from the ED (85%). No patients died from their injuries while they were in the ED. Linear modeling by year revealed a statistically significant increase in distraction injury rates over the years of study (p<0.001 for trend). CONCLUSIONS: The number of ED visits by ambulatory persons injured while being distracted by cell phone use has been increasing. More research is needed to determine the risks associated with walking and talking on a cell phone and to develop strategies for intervention. PRACTICAL APPLICATIONS: Cell phone use continues to increase both at home and outdoor environments. The use of smart phones, with their more enticing features, increases the likelihood of distraction-induced injuries even more. Manufacturers should consider the addition of tools or applications on smart phones to remind users to remain alert to outside auditory stimuli that herald external hazards and to encourage them to not use these devices while engaged in other activities. PMID- 24237867 TI - Pedestrians' estimates of their own nighttime conspicuity are unaffected by severe reductions in headlight illumination. AB - INTRODUCTION: At night pedestrians tend to overestimate their conspicuity to oncoming drivers, but little is known about factors affecting pedestrians' conspicuity estimates. This study examines how headlamp intensity and pedestrians' clothing influence judgments of their own conspicuity. METHOD: Forty eight undergraduate students estimated their own conspicuity on an unilluminated closed road by walking in front of a stationary vehicle to the point at which they judged that they were just recognizable to the driver. Unknown to the participants, high beam intensity was manipulated between subjects by placing neutral density filters on the headlamps. RESULTS: Estimated conspicuity distances did not significantly vary with changes in headlamp intensity even when only 3% of the illumination from the headlamps was present. PRACTICAL APPLICATIONS: These findings underscore the need to educate pedestrians about the visual challenges that drivers face at night and the need to minimize pedestrians' exposure to traffic flow at night. PMID- 24237868 TI - Outcomes associated with breach and fulfillment of the psychological contract of safety. AB - INTRODUCTION: The study investigated the outcomes associated with breach and fulfillment of the psychological contract of safety. METHOD: The psychological contract of safety is defined as the beliefs of individuals about reciprocal employer and employee safety obligations inferred from implicit or explicit promises. When employees perceive that safety obligations promised by the employer have not been met, a breach of the psychological contract occurs, termed employer breach of obligations. The extent to which employees fulfill their safety obligations to the employer is termed employee fulfillment of obligations. Structural equation modeling was used to test a model of safety that investigated the positive and negative outcomes associated with breach and fulfillment of the psychological contract of safety. Participants were 424 health care workers recruited from two hospitals in the State of Victoria, Australia. RESULTS: Following slight modification of the hypothesized model, a good fitting model resulted. Being injured in the workplace was found to lower perceptions of trust in the employer and increase perceptions of employer breach of safety obligations. Trust in the employer significantly influenced perceived employer breach of safety obligations such that lowered trust resulted in higher perceptions of breach. Perceptions of employer breach significantly impacted employee fulfillment of safety obligations with high perceptions of breach resulting in low employee fulfillment of obligations. Trust and perceptions of breach significantly influenced safety attitudes, but not safety behavior. Fulfillment of employee safety obligations significantly impacted safety behavior, but not safety attitudes. Implications of these findings for safety and psychological contract research are explored. A positive emphasis on social exchange relationships in organizations will have positive outcomes for safety climate and safety behavior. PMID- 24237869 TI - Production output pressure and coal mine fatality seasonal variations in China, 2002-2011. AB - INTRODUCTION: The death rate per million tons (DRPMT) is considered as the key index to the quality of coal mine safety management. The index for 2002-2011 revealed a marked improvement in China coal mine safety management during the 10 year period. However, when seasonally adjusted, the 2002-2011 fatality data showed a strong seasonal variation trend. This was reasonably consistent for the 10 years, which suggests that it was always the weak link in Chinese coal mine safety management over that time. However, the overall annual decrease in DRPMT was not reflected by any noticeable improvement in the seasonal occurrence of fatal coal mine accidents in China. METHOD: This paper focuses on this issue, first by analyzing the seasonal fluctuation of fatal accident statistics, then by investigating whether there was a parallel trend in China production output pressure. Finally an error correction model (ECM) was established to analyze the relationship between seasonal fatality rates and the pressure to increase coal production output, and revealed a close relationship between the two. PRACTICAL APPLICATIONS: Firstly, the finding of this paper can help coal mine companies arrange their production planning more rationally, and decrease the fatalities' seasonal variations. Secondly, this paper is also helpful for the government to improve their regulation policies, to control the frequency of seasonal coal mine disasters. PMID- 24237870 TI - Introducing a multivariate model for predicting driving performance: the role of driving anger and personal characteristics. AB - INTRODUCTION: Maladaptive driving is an important source of self-inflicted accidents and this driving style could include high speeds, speeding violations, and poor lateral control of the vehicle. The literature suggests that certain groups of drivers, such as novice drivers, males, highly motivated drivers, and those who frequently experience anger in traffic, tend to exhibit more maladaptive driving patterns compared to other drivers. Remarkably, no coherent framework is currently available to describe the relationships and distinct influences of these factors. METHOD: We conducted two studies with the aim of creating a multivariate model that combines the aforementioned factors, describes their relationships, and predicts driving performance more precisely. The studies employed different techniques to elicit emotion and different tracks designed to explore the driving behaviors of participants in potentially anger-provoking situations. Study 1 induced emotions with short film clips. Study 2 confronted the participants with potentially anger-inducing traffic situations during the simulated drive. RESULTS: In both studies, participants who experienced high levels of anger drove faster and exhibited greater longitudinal and lateral acceleration. Furthermore, multiple linear regressions and path-models revealed that highly motivated male drivers displayed the same behavior independent of their emotional state. The results indicate that anger and specific risk characteristics lead to maladaptive changes in important driving parameters and that drivers with these specific risk factors are prone to experience more anger while driving, which further worsens their driving performance. Driver trainings and anger management courses will profit from these findings because they help to improve the validity of assessments of anger related driving behavior. PMID- 24237871 TI - A comparative analysis of occupational health and safety risk prevention practices in Sweden and Spain. AB - INTRODUCTION: Scandinavian countries such as Sweden implemented the occupational health and safety (OHS) measures in the European Directive 89/391/EEC earlier than other European counties, including Spain. In fact, statistics on workplace accident rates reveal that between 2004 and 2009, there were considerably fewer accidents in Sweden than in Spain. METHOD: The objective of the research described in this paper was to reduce workplace accidents and to improve OHS management in Spain by exploring the OHS practices in Sweden. For this purpose, an exploratory comparative study was conducted, which focused on the effectiveness of the EU directive in both countries. The study included a cross sectional analysis of workplace accident rates and other contextual indicators in both national contexts. A case study of 14 Swedish and Spanish companies identified 14 differences in the preventive practices implemented. These differences were then assessed with a Delphi study to evaluate their contribution to the reduction of workplace accidents and their potential for improving health and safety management in Spain. RESULTS: The results showed that there was agreement concerning 12 of the 14 practices. Finally, we discuss opportunities of improvement in Spanish companies so that they can make their risk management practices more effective. PRACTICAL APPLICATIONS: The findings of this comparative study on the implementation of the European Directive 89/391/EEC in both Sweden and Spain have revealed health and safety managerial practices which, if properly implemented, could contribute to improved work conditions and accident statistics of Spanish companies. In particular, the results suggest that Spanish employers, safety managers, external prevention services, safety deputies and Labour Inspectorates should consider implementing streamlined internal preventive management, promoting the integration of prevention responsibilities to the chain of command, and preventing health and safety management from becoming a mere exchange of documents. The authors also encourage future research studies to use the methodology presented to compare and assess the European Directive 89/391/EEC implementation in other European countries. PMID- 24237872 TI - Exploring the risk factors associated with the size and severity of roadway crashes in Riyadh. AB - INTRODUCTION: Recently, growing concern has been shifting toward the necessity of improving traffic safety in the Kingdom of Saudi Arabia (KSA). KSA has a unique traffic safety problem in that: (a) it can be classified as a developed country in terms of the magnitude and quality of the roadway networks available and its compatibility with international standards; however, (b) it can also be considered a developing country as the rate of increase in the number of road crashes is substantial compared with relevant figures of other developing countries and other countries of the Gulf region. Hence, more research efforts are still needed. OBJECTIVES: This paper examines the nature and causes of fatal and serious traffic crashes in KSA so that solutions and/or future studies can be suggested. METHOD: Data from 11,545 reported fatal and injury traffic crashes that occurred in Riyadh (the capital of KSA) during the period 2004-2011 were analyzed by alternative and complementary methods. A logistic regression model was estimated and the results revealed that crash reason (speeding), damages in public property, day of the week, crash location (non-intersection location), and point of collision (head-on) were the significant variables affecting the binary target variable (fatal and non-fatal crashes). Additionally, the structural equation modeling approach was developed to identify and quantify the impacts of significant variables influencing crash size (e.g., no. of injuries, no. of vehicles involved in the crash). Crash size is one of the important indices that measure the level of safety of transportation facilities. RESULTS: The results showed that road factor was the most significant factor affecting the size of the crash followed by the driver and environment factors. IMPACT ON INDUSTRY: Considering the results of this study, practical suggestions on how to improve traffic safety in KSA are also presented and discussed. PMID- 24237873 TI - How perceptions of experience-based analysis influence explanations of work accidents. AB - INTRODUCTION: This article looks into how perceptions of experience-based analysis (EBA) influence causal explanations of accidents given by managers and workers in the chemical industry (n=409) and in the nuclear industry (n=222). METHOD: The approach is based on the model of naive explanations of accidents (Kouabenan, 1999, 2006, 2009), which recommends taking into account explanations of accidents spontaneously given by individuals, including laypersons, not only to better understand why accidents occur but also to design and implement the most appropriate prevention measures. The study reported here describes the impact of perceptions about EBA (perceived effectiveness, personal commitment, and the feeling of being involved in EBA practices) on managers' and workers' explanations of accidents likely to occur at the workplace. RESULTS: The results indicated that both managers and workers made more internal explanations than external ones when they perceived EBA positively. Moreover, the more the participants felt involved in EBA, were committed to it, and judged it effective, the more they explained accidents in terms of factors internal to the workers. PRACTICAL APPLICATIONS: Recommendations are proposed for reducing defensive reactions, increasing personal commitment to EBA, and improving EBA effectiveness. PMID- 24237874 TI - Is more engaging safety training always better in reducing accidents? Evidence of self-selection from Chilean panel data. AB - INTRODUCTION: The recent events in Chile involving 33 miners who were trapped and rescued in the San Jose mine led the government to strongly promote occupational safety and health (OSH) training. However, there is an ongoing debate regarding which type of training is the most effective in reducing accidents. METHOD: The "engagement hypothesis" claims that traditional classrooms are rather ineffective and that only a strong student involvement may generate meaningful results, but the empirical evidence is inconclusive. To contribute to this debate, we claim that the selection of the training method may be contingent on the firm's OSH capabilities and commitment. Firms with fewer (greater) capabilities may optimally self-select less (more) engaging training methods. RESULTS: Accordingly, based on panel data from 2003 to 2009 for a representative sample of 2,787 Chilean firms, the engagement hypothesis initially appears to be supported; however, after correcting for self-selection bias, it loses most of its significance. IMPACT ON INDUSTRY: Chilean policymakers are strongly advised to expand OSH training. PMID- 24237875 TI - Travel-related behaviors, opinions, and concerns of U.S. adult drivers by race/ethnicity, 2010. AB - INTRODUCTION: The U.S. population is shifting to become both older and more racially and ethnically diverse. Our current understanding of U.S. drivers' travel-related needs and concerns by race/ethnicity is limited. METHODS: Data from the 2010 HealthStyles survey, an annual, cross-sectional, national mail panel survey of persons ages 18 years or older living in the United States, were used to calculate weighted percentages of travel-related behaviors, opinions, and concerns by race/ethnicity. Logistic regression was used to explore associations between race/ethnicity and specific travel-related concerns, while adjusting for other demographic characteristics. RESULTS: Adequate transportation alternatives to driving were reported by a greater percentage of persons in certain minority groups compared to whites (Hispanic: 34.7%; white: 23.4%). Concern for the availability of alternatives to driving in the future was greater among minority groups (black: 57.7%; Hispanic: 47.3%; other: 50.9%) compared to whites (37.5%). Additionally, among persons with a household income of $25,000+, minorities were generally more likely than whites to report concern about having alternative transportation options to driving, whereas concern was consistently high among all racial/ethnic groups for those earning less than $25,000 annually. In each racial/ethnic group, more than 10% of persons reported not knowing how they would get around if they could no longer drive. CONCLUSIONS: Important variations by race/ethnicity in both travel behaviors and concerns for adequate alternatives to driving were found, revealing the need for further research to better understand reasons for these differences and to identify ways to meet the transportation needs of the changing U.S. population demographics. IMPACT ON INDUSTRY: Further research on adequate alternatives to driving and transportation needs is needed. PMID- 24237876 TI - Physical activity level and its clinical correlates in chronic obstructive pulmonary disease: a cross-sectional study. AB - BACKGROUND: Decreased physical activity is associated with higher mortality in subjects with COPD. The aim of this study was to assess clinical characteristics and physical activity levels (PALs) in subjects with COPD. METHODS: Seventy-three subjects with COPD (67 +/- 7 yrs, 44 female) with one-second forced expiratory volume percentage (FEV1%) predicted values of 43 +/- 16 were included. The ratio of total energy expenditure (TEE) and resting metabolic rate (RMR) was used to define the physical activity level (PAL) (PAL = TEE/RMR). TEE was assessed with an activity monitor (ActiReg), and RMR was measured by indirect calorimetry. Walking speed (measured over 30-meters), maximal quadriceps muscle strength, fat free mass and systemic inflammation were measured as clinical characteristics. Hierarchical linear regression was applied to investigate the explanatory values of the clinical correlates to PAL. RESULTS: The mean PAL was 1.47 +/- 0.19, and 92% of subjects were classified as physically very inactive or sedentary. The walking speed was 1.02 +/- 0.23 m/s, the quadriceps strength was 31.3 +/- 11.2 kg, and the fat-free mass index (FFMI) was 15.7 +/- 2.3 kg/m2, identifying 42% of subjects as slow walkers, 21% as muscle-weak and 49% as FFM-depleted. The regression model explained 45.5% (p < 0.001) of the variance in PAL. The FEV1% predicted explained the largest proportion (22.5%), with further improvements in the model from walking speed (10.1%), muscle strength (7.0%) and FFMI (3.0%). Neither age, gender nor systemic inflammation contributed to the model. CONCLUSIONS: Apart from lung function, walking speed and muscle strength are important correlates of physical activity. Further explorations of the longitudinal effects of the factors characterizing the most inactive subjects are warranted. PMID- 24237877 TI - Reference management software for systematic reviews and meta-analyses: an exploration of usage and usability. AB - BACKGROUND: Reference management software programs enable researchers to more easily organize and manage large volumes of references typically identified during the production of systematic reviews. The purpose of this study was to determine the extent to which authors are using reference management software to produce systematic reviews; identify which programs are used most frequently and rate their ease of use; and assess the degree to which software usage is documented in published studies. METHODS: We reviewed the full text of systematic reviews published in core clinical journals indexed in ACP Journal Club from 2008 to November 2011 to determine the extent to which reference management software usage is reported in published reviews. We surveyed corresponding authors to verify and supplement information in published reports, and gather frequency and ease-of-use data on individual reference management programs. RESULTS: Of the 78 researchers who responded to our survey, 79.5% reported that they had used a reference management software package to prepare their review. Of these, 4.8% reported this usage in their published studies. EndNote, Reference Manager, and RefWorks were the programs of choice for more than 98% of authors who used this software. Comments with respect to ease-of-use issues focused on the integration of this software with other programs and computer interfaces, and the sharing of reference databases among researchers. CONCLUSIONS: Despite underreporting of use, reference management software is frequently adopted by authors of systematic reviews. The transparency, reproducibility and quality of systematic reviews may be enhanced through increased reporting of reference management software usage. PMID- 24237878 TI - Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behcet's disease. AB - OBJECTIVES: To investigate the pathophysiology of Behcet's disease (BD) and find biomarkers for the disease, we analysed protein profiles of peripheral blood mononuclear cells (PBMCs). METHODS: Proteins, extracted from PBMCs, were comprehensively analysed in 16 patients with BD, 16 patients with rheumatoid arthritis (RA), 12 patients with Crohn's disease (CD), and 16 healthy control subjects (HC) by 2-dimensional differential gel electrophoResis (2D-DIGE). Differently expressed proteins were identified by mass spectrometry. RESULTS: 563 protein spots were detected. We completely discriminated between the BD and HC groups, between the BD and RA groups, and between the BD and CD groups by multivariate analysis of intensity of 23, 35, and 1 spots, respectively. The spots contributing to the differences included proteins related to cytoskeleton, transcription/translation, T cell activation, bone turnover, regulating apoptosis, and microbial infection. Intensity of 3 spots (tyrosine-protein phosphatase non-receptor type 4, threonine synthase-like 2, and beta-actin) provided area under the receiver operating characteristic curves (AUROC) of 0.889 for discrimination between the BD group and the non-BD groups. Informatively, intensity of the above 1 spot completely discriminated the CD group from the other groups (AUROC 1.000). This spot, identified as beta-actin, had different pI from the above beta-actin-spot probably due to different post-translational modification. CONCLUSIONS: PBMC protein profiles, especially the profile of the 3 spots, would be candidate biomarkers for BD. The latter beta-actin subtype would be useful for discriminating inflammatory bowel diseases from BD and other diseases. The identified proteins may play important roles in the pathophysiology of BD. PMID- 24237879 TI - Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: a double-blinded randomized controlled trial. AB - BACKGROUND: This prospective, randomized, double-blind study was designed to evaluate the use of intranasally administered dexmedetomidine vs intranasal midazolam as a premedication in children undergoing complete dental rehabilitation. METHODS: Seventy-two children of American Society of Anesthesiology classification (ASA) physical status (I & II), aged 3-6 years, were randomly assigned to one of two equal groups. Group M received intranasal midazolam (0.2 mg.kg(-1)), and group D received intranasal dexmedetomidine (1 MUg.kg(-1)). The patients' sedation status, mask acceptance, and hemodynamic parameters were recorded by an observer until anesthesia induction. Recovery conditions, postoperative pain, and postoperative agitation were also recorded. RESULTS: The median onset of sedation was significantly shorter in group M 15 (10 25) min than in group D 25 (20-40) min (P = 0.001). Compared with the children in group M, those in group D were significantly more sedated when they were separated from their parents (77.8% vs 44.4%, respectively) (P = 0.002). Satisfactory compliance with mask application was 58.3% in group M vs 80.6% in group D (P = 0.035). The incidences of postoperative agitation and shivering were significantly lower in Group D compared with group M. Thirteen children (36.1%) in group M, showed signs of nasal irritation with teary eyes, and none of these signs was seen in the children in group D (P = 0.000). There were no incidences of bradycardia, hypotension, in either of the groups during study observation. CONCLUSION: Intranasal dexmedetomidine (1 MUg.kg(-1)) is an effective and safe alternative for premedication in children; it resulted in superior sedation in comparison to 0.2 mg.kg(-1) intranasal midazolam. However, it has relatively prolonged onset of action. PMID- 24237881 TI - Fusion-optimized intervals (FOI): a new method to achieve the narrowest QRS for optimization of the AV and VV intervals in patients undergoing cardiac resynchronization therapy. AB - BACKGROUND: Optimization of atrioventricular (AV) and interventricular (VV) intervals may improve cardiac resynchronization therapy (CRT) response but is a complex task. Fusion with intrinsic conduction may increase the benefit of CRT. The aim was to describe fusion-optimized intervals (FOI), a new method of optimizing CRT based on QRS duration. METHODS AND RESULTS: Seventy-six consecutive patients with preserved AV conduction who received CRT were prospectively included. The AV interval was optimized by searching the narrowest QRS obtained within the fusion band during left ventricular (LV) pacing. The VV interval was then adjusted, comparing QRS duration in simultaneous biventricular, LV preexcitation (-30 milliseconds), right ventricular (RV) preexcitation (-30 milliseconds) and LV-only pacing. A substudy in 31 patients evaluated the invasive LV +dP/dtmax . The best fusion-optimized AV interval was 136 +/- 30 milliseconds during atrial sensing and 192 +/- 35 milliseconds during atrial pacing. The best QRS was obtained with simultaneous biventricular pacing in 28 patients (37%), LV preexcitation in 22 (29%), LV-only in 20 (26%), and RV preexcitation in 6 (8%). Baseline QRS was shortened more by FOI (59 +/- 19 milliseconds) than by nominal settings (40 +/- 21 milliseconds; P < 0.001). Sixty five patients (86%) showed >10% shortening of the baseline QRS with FOI; none prolonged the QRS duration by FOI compared to nominal settings. All echocardiographic asynchrony parameters were corrected by FOI. Baseline +dP/dtmax improvement was greater in FOI (127 +/- 95 mmHg/seconds) than in nominal settings (102 +/- 71 mmHg/seconds; P = 0.05). CONCLUSION: The FOI method is feasible, further reduces QRS duration, and improves acute hemodynamic response compared to nominal programming of CRT. PMID- 24237880 TI - Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water. AB - BACKGROUND: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest. METHODS: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 MUg/L versus >=1 MUg/L. RESULTS: As expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (>=1 MUg/L). CONCLUSIONS: This study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential health risk. PMID- 24237882 TI - Nurse burnout: personal and environmental factors as predictors. AB - The aim of this study is to investigate the level of burnout of clinical nurses and to examine the influence of personal and environmental factors on nurse burnout. A total of 717 full-time nurses from six hospitals in Tianjin, China, completed five questionnaires: a demographic questionnaire, the Maslach Burnout Inventory, the General Self-Efficacy Scale, the Practice Environment Scale of the Nursing Work Index and the Nurse Job Stressor Scale. The participants had moderate levels of emotional exhaustion (mean score 23.95 +/- 11.11) and depersonalization (mean score 7.90 +/- 6.58) and a high level of reduced personal accomplishment (mean score 27.51 +/- 10.96). Both personal and environmental factors were correlated with nurse burnout; however, personal factors played bigger roles in predicting personal accomplishment, whereas environmental factors played bigger roles in predicting emotional exhaustion and depersonalization. In order to reduce nurse job burnout effectively, administrators should pay more attention to the improvement of nurses' self-efficacy and professional nursing practice environment and the reduction of stressors. PMID- 24237883 TI - Structural updates of alignment of protein domains and consequences on evolutionary models of domain superfamilies. AB - BACKGROUND: Influx of newly determined crystal structures into primary structural databases is increasing at a rapid pace. This leads to updation of primary and their dependent secondary databases which makes large scale analysis of structures even more challenging. Hence, it becomes essential to compare and appreciate replacement of data and inclusion of new data that is critical between two updates. PASS2 is a database that retains structure-based sequence alignments of protein domain superfamilies and relies on SCOP database for its hierarchy and definition of superfamily members. Since, accurate alignments of distantly related proteins are useful evolutionary models for depicting variations within protein superfamilies, this study aims to trace the changes in data in between PASS2 updates. RESULTS: In this study, differences in superfamily compositions, family constituents and length variations between different versions of PASS2 have been tracked. Studying length variations in protein domains, which have been introduced by indels (insertions/deletions), are important because theses indels act as evolutionary signatures in introducing variations in substrate specificity, domain interactions and sometimes even regulating protein stability. With this objective of classifying the nature and source of variations in the superfamilies during transitions (between the different versions of PASS2), increasing length-rigidity of the superfamilies in the recent version is observed. In order to study such length-variant superfamilies in detail, an improved classification approach is also presented, which divides the superfamilies into distinct groups based on their extent of length variation. CONCLUSIONS: An objective study in terms of transition between the database updates, detailed investigation of the new/old members and examination of their structural alignments is non-trivial and will help researchers in designing experiments on specific superfamilies, in various modelling studies, in linking representative superfamily members to rapidly expanding sequence space and in evaluating the effects of length variations of new members in drug target proteins. The improved objective classification scheme developed here would be useful in future for automatic analysis of length variation in cases of updates of databases or even within different secondary databases. PMID- 24237884 TI - Optical tomographic imaging of near infrared imaging agents quantifies disease severity and immunomodulation of experimental autoimmune encephalomyelitis in vivo. AB - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal model that captures many of the hallmarks of human multiple sclerosis (MS), including blood-brain barrier (BBB) breakdown, inflammation, demyelination and axonal destruction. The standard clinical score measurement of disease severity and progression assesses functional changes in animal mobility; however, it does not offer information regarding the underlying pathophysiology of the disease in real time. The purpose of this study was to apply a novel optical imaging technique that offers the advantage of rapid imaging of relevant biomarkers in live animals. METHODS: Advances in non-invasive fluorescence molecular tomographic (FMT) imaging, in combination with a variety of biological imaging agents, offer a unique, sensitive and quantifiable approach to assessing disease biology in living animals. Using vascular (AngioSense 750EX) and protease-activatable cathepsin B (Cat B 680 FAST) near infrared (NIR) fluorescence imaging agents to detect BBB breakdown and inflammation, respectively, we quantified brain and spinal cord changes in mice with relapsing-remitting PLP139-151-induced EAE and in response to tolerogenic therapy. RESULTS: FMT imaging and analysis techniques were carefully characterized and non-invasive imaging results corroborated by both ex vivo tissue imaging and comparison to clinical score results and histopathological analysis of CNS tissue. FMT imaging showed clear differences between control and diseased mice, and immune tolerance induction by antigen coupled PLGA nanoparticles effectively blocked both disease induction and accumulation of imaging agents in the brain and spinal cord. CONCLUSIONS: Cat B 680 FAST and AngioSense 750EX offered the combination best able to detect disease in both the brain and spinal cord, as well as the downregulation of disease by antigen-specific tolerance. Non-invasive optical tomographic imaging thus offers a unique approach to monitoring neuroinflammatory disease and therapeutic intervention in living mice with EAE. PMID- 24237886 TI - Sternal elevation before passing bars: a technique for improving visualization and facilitating minimally invasive pectus excavatum repair in adult patients. PMID- 24237885 TI - Aprotinin, but not epsilon-aminocaproic acid and tranexamic acid, exerts neuroprotection against excitotoxic injury in an in vitro neuronal cell culture model. AB - OBJECTIVE: Lack of availability of aprotinin has resulted in increased clinical use of the alternative antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), which are known to be associated with an increased risk of seizures. In contrast, aprotinin has previously been demonstrated to be neuroprotective through suppression of excitotoxicity-mediated neuronal degeneration via the extracellular plasminogen/plasmin system. This study compares the effect of antifibrinolytic agents on neuronal and mixed glial/neuronal cell cultures. METHODS: Mixed cortical cultures containing neuronal and glial cells were prepared from fetal mice and plated on a layer of confluent astrocytes from postnatal pups. A primary neuronal culture was obtained from the same gestational stage and plated in multiwall vessels. Slowly triggered excitotoxicity was induced by 24-hour exposure to 12.5 mM N-methyl-D-aspartate (NMDA). Apoptotic neuronal cell death was induced by exposure of primary neural cultures to 24 hours of serum deprivation. RESULTS: Compared with NMDA alone, no significant changes in cell death were observed for any dose of TXA or EACA in mixed cultures. Conversely, a clinical dose of aprotinin significantly reduced cell death by -31% on average. Aprotinin reduced apoptotic neuronal cell death from 75% to 37.3%, and to 34.1% at concentrations of 100 and 200 kIU/mL, respectively, and significantly decreased neuronal nuclear damage. These concentrations of aprotinin significantly inhibited caspase 9 and 3/7 activations; 250 kIU/mL aprotinin exerted maximal protection on primary cortical neurons. CONCLUSIONS: In contrast to aprotinin, EACA and TXA exert no protective effect against excitotoxic neuronal injury that can occur during cardiac surgery. PMID- 24237887 TI - Nonablative fractional resurfacing for the treatment of iatrogenic hypopigmentation. PMID- 24237889 TI - Controlling antimicrobial resistance: Interfering in the process of natural selection. PMID- 24237890 TI - The influence of whole body vibration on the central and peripheral cardiovascular system. AB - The purpose of this study was to investigate the physiological changes of the cardiovascular system in response to whole body vibration during quiet standing and identify whether there is a greater influence on the central or peripheral cardiovascular system. Twenty healthy participants (12 male and 8 female) were assessed over two separate testing sessions for changes in peripheral skin temperature, peripheral venous function, blood flow velocity in the dorsalis pedis artery, blood pressure and heart rate during quiet standing with 40 Hz 1.9 mm synchronous vibration. Vibration exposure totalled 5 min in 1 min increments with 5 min recovery during each testing session. There were no significant changes in heart rate, blood pressure or peripheral skin temperature. Significant results were obtained for blood flow velocity with increases from 0.5 + 0.2 cm.s( 1) at baseline to 1 + 0.2 cm.s(-1) during vibration, returning to baseline levels during the recovery period. Due to the absence of changes in heart rate, blood pressure or lower leg and foot temperature, the change in blood flow velocity can be attributed to changes in peripheral vascular function. The results suggest a high level of sensitivity of the peripheral vascular system to vibration exposure; therefore, further studies should be completed to ascertain the physiological mechanisms underlying the effects of vibration on the peripheral vascular system. PMID- 24237891 TI - Portal biliopathy: multidisciplinary management and outcomes of treatment. AB - INTRODUCTION: Portal biliopathy (PB) is a rare condition in which portal hypertension because of extrahepatic portal vein obstruction can lead to biliary abnormalities, with some patients developing obstructive jaundice. At present, there is no international consensus on the management of PB. We present the experience of an Australian tertiary referral hospital with the diagnosis and management of PB, and compare this with reported international experience. METHODS: The records of nine patients presenting with PB between June 2003 and March 2012 were reviewed and analysed. RESULTS: All patients had portal hypertension because of portal vein thrombosis, with seven patients showing cavernous transformation of the portal vein. Biliary abnormality presented with jaundice (3/9), abdominal pain (2/9) or without symptoms (3/9). All patients developed a cholestatic pattern of liver function tests (LFTs). First-line endoscopic management was employed in 7 of 8 symptomatic patients. Four patients required endoscopic management alone (sphincterotomy alone (1/9), single stent (2/9), repeated stent changes (1/9) ), while four required second-line surgical intervention (portosystemic shunt (1/9), bilioenteric anastomosis (3/9) ). All patients were well, with stable LFTs, at median 18-month follow-up, with two patients undergoing regular stent changes, and the remainder requiring no further intervention. CONCLUSION: PB can be managed successfully with endoscopic therapy as the first-line option, but a multidisciplinary approach is necessary, with second-line surgical intervention often required. We recommend a management algorithm similar to that presented in the UK PB literature, and confirm that bilioenteric anastomosis can be performed successfully without prior portal decompression. PMID- 24237892 TI - Who is responsible for the public's health? The role of the alcohol industry in the WHO global strategy to reduce the harmful use of alcohol. PMID- 24237893 TI - Unrecorded alcohol: significant neglected challenges. PMID- 24237894 TI - The role of the comparison group in epidemiology and general limitations. PMID- 24237895 TI - Alcohol as a panacea: Limitations of observational studies. PMID- 24237896 TI - Response to commentaries. PMID- 24237897 TI - Commentary on Heckman et al. (2013): Negative affect increases craving-Questions about the relationship of affect, craving and smoking. PMID- 24237898 TI - Commentary on Wang et al. (2013): Time to test the mechanisms of alcohol outlet density effects. PMID- 24237899 TI - Commentary on Tuithof et al. (2013): Implications of the DSM-5 revision for the analysis of persistence/remission of alcohol use disorder. PMID- 24237900 TI - Commentary on Heron et al. (2013): Findings on associations between conduct problem trajectories, early risk factors and adolescent cannabis use-how do they fit with existing theories? PMID- 24237901 TI - Commentary on Rosenthal et al. (2013): Buprenorphine implant-new hopes, old questions. PMID- 24237903 TI - The degradation (by distinct pathways) of human D-amino acid oxidase and its interacting partner pLG72--two key proteins in D-serine catabolism in the brain. AB - Human D-amino acid oxidase (EC 1.4.3.3; hDAAO) is a peroxisomal flavoenzyme significantly enriched in the mammalian brain. hDAAO has been proposed to play (with serine racemase; EC 5.1.1.18) an essential role in the catabolism of D serine, an 'atypical' key signalling molecule that acts as allosteric activator of the N-methyl-D-aspartate-type glutamate receptor (NMDAr). hDAAO and its interacting partner pLG72 have been related to schizophrenia, a highly disabling psychiatric disorder in which a dysfunction of NMDA-mediated neurotransmission is widely assumed to occur. We previously demonstrated that the D-serine cellular concentration depends on hDAAO and pLG72 expression levels and that newly synthesized hDAAO interacts with its modulator in the cytosol, being progressively destabilized and inactivated. To obtain insight into the mechanisms regulating cellular D-serine levels, we investigated the degradation pathways of hDAAO and pLG72 in U87 glioblastoma cells stably expressing enhanced yellow fluorescent protein-hDAAO (peroxisomal), hDAAO-enhanced yellow fluorescent protein (cytosolic) or pLG72-enhanced cyan fluorescent protein (mitochondrial) proteins. hDAAO is a long-lived protein: the peroxisomal fraction of this flavoprotein is degraded via the lysosomal/endosomal pathway (and blocking this pathway increases the cellular hDAAO activity and decreases D-serine levels), whereas the cytosolic portion is ubiquitinated and targeted to the proteasome. By contrast, pLG72 shows a rapid turnover (t(1/2) ~ 25-40 min) and is degraded via the proteasome system, albeit not ubiquitinated. Overexpression of pLG72 increases the turnover of hDAAO, in turn playing a protective role against excessive D-serine depletion. PMID- 24237904 TI - SNPMeta: SNP annotation and SNP metadata collection without a reference genome. AB - The increase in availability of resequencing data is greatly accelerating SNP discovery and has facilitated the development of SNP genotyping assays. This, in turn, is increasing interest in annotation of individual SNPs. Currently, these data are only available through curation, or comparison to a reference genome. Many species lack a reference genome, but are still important genetic models or are significant species in agricultural production or natural ecosystems. For these species, it is possible to annotate SNPs through comparison with cDNA, or data from well-annotated genes in public repositories. We present SNPMeta, a tool which gathers information about SNPs by comparison with sequences present in GenBank databases. SNPMeta is able to annotate SNPs from contextual sequence in SNP assay designs, and SNPs discovered through genotyping by sequencing (GBS) approaches. However, SNPs discovered through GBS occur throughout the genome, rather than only in gene space, and therefore do not annotate at high rates. SNPMeta can therefore be used to annotate SNPs in nonmodel species or species that lack a reference genome. Annotations generated by SNPMeta are highly concordant with annotations that would be obtained from a reference genome. PMID- 24237906 TI - Unveiling the remodeled atrium: lessons from the early recurrence of atrial fibrillation. PMID- 24237905 TI - Identification of single nucleotide polymorphisms from the transcriptome of an organism with a whole genome duplication. AB - BACKGROUND: The common ancestor of salmonid fishes, including rainbow trout (Oncorhynchus mykiss), experienced a whole genome duplication between 20 and 100 million years ago, and many of the duplicated genes have been retained in the trout genome. This retention complicates efforts to detect allelic variation in salmonid fishes. Specifically, single nucleotide polymorphism (SNP) detection is problematic because nucleotide variation can be found between the duplicate copies (paralogs) of a gene as well as between alleles. RESULTS: We present a method of differentiating between allelic and paralogous (gene copy) sequence variants, allowing identification of SNPs in organisms with multiple copies of a gene or set of genes. The basic strategy is to: 1) identify windows of unique cDNA sequences with homology to each other, 2) compare these unique cDNAs if they are not shared between individuals (i.e. the cDNA is homozygous in one individual and homozygous for another cDNA in the other individual), and 3) give a "SNP score" value between zero and one to each candidate sequence variant based on six criteria. Using this strategy we were able to detect about seven thousand potential SNPs from the transcriptomes of several clonal lines of rainbow trout. When directly compared to a pre-validated set of SNPs in polyploid wheat, we were also able to estimate the false-positive rate of this strategy as 0 to 28% depending on parameters used. CONCLUSIONS: This strategy has an advantage over traditional techniques of SNP identification because another dimension of sequencing information is utilized. This method is especially well suited for identifying SNPs in polyploids, both outbred and inbred, but would tend to be conservative for diploid organisms. PMID- 24237907 TI - Postoperative hemorrhage risk after outpatient dermatologic surgery procedures. PMID- 24237908 TI - Moving on.... PMID- 24237909 TI - Transforming preventive medicine science, practice, education, and policy: looking back at the last 20 years of the American Journal of Preventive Medicine. PMID- 24237910 TI - Notes from the field: planting, nurturing, and watching things grow. AB - Editors' Note: We invited a sample of AJPM's Editorial Board, supplement guest editors, and longtime colleagues and contributors to share their experiences and impressions of the impact of AJPM on their respective domains. We were particularly fond of Ken Powell's analogy to being "tenders of the planted seed"- as planters, weeders, and harvesters--watching and nurturing the growth of AJPM, and have elected to lead with his commentary. PMID- 24237911 TI - Biomarkers of tobacco smoke exposure and asthma severity in adults. AB - BACKGROUND: Tobacco biomarkers including serum cotinine and urinary 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) have been used in research settings. PURPOSE: The goal of the study was to examine the association of cotinine and NNAL with asthma outcomes in the U.S. adult population. METHODS: A cross-sectional design was used, using data from the National Health and Nutrition Examination Survey, 2007-2008, with participants aged >20 years with self-reported asthma (N=456). Past-year asthma exacerbations and emergency room/urgent care visits for asthma were examined. Analyses were conducted in 2013. RESULTS: Among adult asthmatics, 50.3% reported a past-year asthma attack (61.8% smokers, 46.6% nonsmokers, p=0.029). Among these, 24.7% reported a past year emergency/urgent visit for asthma (34.7% smokers, 20.1% nonsmokers, p=0.034). Median concentrations of cotinine and creatinine-adjusted NNAL (NNAL/Cr) were significantly higher in those with a past-year asthma attack (0.43 ng/mL and 7.28 pg/mL) than in those without (0.06 ng/mL and 2.26 pg/mL), and highest in those with past-year emergency/urgent visits (0.93 ng/mL and 28.14 pg/mL). Among nonsmokers, increasing levels of log cotinine or log NNAL/Cr, adjusted for demographics, were significantly associated with past-year asthma exacerbation (log cotinine OR=1.46 [95% CI=1.1, 1.92]; log NNAL/Cr OR=1.42 [95% CI=1.07, 1.88]) and past-year emergency/urgent visit (log cotinine OR=1.95 [95% CI=1.32, 2.88]; log NNAL/Cr OR=1.58 [95% CI=1.23, 2.02]). Among smokers, increasing biomarker levels were not significantly associated with either outcome. CONCLUSIONS: In a population-based cross-sectional analysis, increased cotinine and NNAL were found to be associated with asthma exacerbation and healthcare use in nonsmokers with asthma. If these findings are confirmed in prospective studies, these biomarkers might be candidates for clinical indicators of risk of asthma. PMID- 24237912 TI - Customer responses to mandatory menu labeling at full-service restaurants. AB - BACKGROUND: In 2010, Philadelphia enacted a menu-labeling law requiring full service restaurant chains to list values for calories, sodium, fat, and carbohydrates for each item on all printed menus. PURPOSE: The goal of the study was to determine whether purchase decisions at full-service restaurants varied depending on the presence of labeling. METHODS: In August 2011, this cross sectional study collected 648 customer surveys and transaction receipts at seven restaurant outlets of one large full-service restaurant chain. Two outlets had menu labeling (case sites); five outlets did not (control sites). Outcomes included differences in calories and nutrients purchased and customers' reported use of nutrition information when ordering. Data were analyzed in 2012. RESULTS: Mean age was 37 years; 60% were female; 50% were black/African-American and reported incomes >=$60,000. Customers purchased food with approximately 1600 kcal (food plus beverage, 1800 kcal); 3200 mg sodium; and 35 g saturated fat. After adjustment for confounders, customers at labeled restaurants purchased food with 151 fewer kilocalories (95% CI=-270, -33); 224 mg less sodium (95% CI=-457, +8); and 3.7 g less saturated fat (95% CI=-7.4, -0.1) compared to customers at unlabeled restaurants (or 155 less kilocalories from food plus beverage, 95% CI= 284, -27). Those reporting that nutrition information affected their order purchased 400 fewer food calories, 370 mg less sodium, and 10 g less saturated fat. CONCLUSIONS: Mandatory menu labeling was associated with better food choices among a segment of the public dining at full-service restaurants. Consumer education on the availability and use of nutrition information may extend the impact of menu labeling. PMID- 24237913 TI - Local health department activities to ensure access to care. AB - BACKGROUND: Local health departments (LHDs) can play an important role in linking people to personal health services and ensuring the provision of health care when it is otherwise unavailable. However, the extent to which LHDs are involved in ensuring access to health care in its jurisdictions is not well known. PURPOSE: To provide nationally representative estimates of LHD involvement in specific activities to ensure access to healthcare services and to assess their association with macro-environment/community and LHD capacity and process characteristics. METHODS: Data used were from the 2010 National Profile of Local Health Departments Study, Area Resource Files, and the Association of State and Territorial Health Officials' 2010 Profile of State Public Health Agencies Survey. Data were analyzed in 2012. RESULTS: Approximately 66.0% of LHDs conducted activities to ensure access to medical care, 45.9% to dental care, and 32.0% to behavioral health care. About 28% of LHDs had not conducted activities to ensure access to health care in their jurisdictions in 2010. LHDs with higher per capita expenditures and larger jurisdiction population sizes were more likely to provide access to care services (p <0.05). CONCLUSIONS: There is substantial variation in LHD engagement in activities to ensure access to care. Differences in LHD capacity and the needs of the communities in which they are located may account for this variation. Further research is needed to determine whether this variation is associated with adverse population health outcomes. PMID- 24237914 TI - Triple tobacco screen: opportunity to help families become smokefree. AB - BACKGROUND: American Academy of Pediatrics policy recommends that pediatricians document environmental tobacco smoke (ETS) exposure of a child at every visit. The extent to which pediatricians adhere to this policy, however, is unknown. PURPOSE: The goal of the study was to examine the extent to which pediatricians screen parents for tobacco use and home- and car-related smoking rules. Further, the potential association between factors associated with pediatrician inquiry into parental tobacco use and rules is examined. METHODS: Post-visit exit interviews were conducted in ten pediatric practices between June 2009 and March 2011 with parents whose children had been seen by a healthcare provider. Parents were considered to have been given the "triple tobacco screen" if they reported being asked by a pediatric healthcare provider about their smoking behavior, smokefree home rules, and smokefree car rules. Bivariate analysis and multivariable logistic regression was done to explore factors associated with parents being given any component of the triple tobacco screening. Data were analyzed between March 2012 and February 2013. RESULTS: Of 9145 parents interviewed, 20% of the parents reported being asked at least one question from the triple tobacco screen, and only 9% reported being asked all three questions. Overall, 17% of parents reported being asked about their smoking status, 16% about smokefree home rules, and 11% about smokefree car rules. Few smoking parents (23%) and fewer nonsmoking parents (19%) were screened about their tobacco use and behavior. CONCLUSIONS: Pediatricians infrequently addressed ETS exposure of children among parents who do and do not smoke. Substantial missed opportunities may exist to counsel smokers and reduce ETS exposure of children in the most common exposure locations-the home and car. PMID- 24237915 TI - A content analysis of popular smartphone apps for smoking cessation. AB - BACKGROUND: Smartphone applications (apps) are increasingly available for smoking cessation. PURPOSE: This study examined the content of popular apps for smoking cessation for both iPhone and Android operating systems in February 2012. METHODS: A total of 252 smoking-cessation apps were identified for the iPhone and 148 for the Android. Across both operating systems, the most popular apps were identified (n=47 for the iPhone and n=51 for the Android) and analyzed for their (1) approach to smoking cessation and (2) adherence to an index based on the U.S. Public Health Service's Clinical Practice Guidelines for Treating Tobacco Use and Dependence. Where available, apps were coded for frequency of downloads. The analysis took place in 2012. RESULTS: Overall, popular apps have low levels of adherence, with an average score of 12.9 of a possible 42 on the Adherence Index. No apps recommended calling a quitline, and only a handful of apps recommended using approved medications (4.1%). Android apps in the sample were downloaded worldwide between 310,800 and 1,248,000 times per month. For both the iPhone and Android, user ratings were positively associated with scores on the Adherence Index. For the iPhone, display order was also positively associated with scores on the Adherence Index. CONCLUSIONS: Apps could be improved by better integration with the Clinical Practice Guidelines and other evidence-based practices. PMID- 24237917 TI - The trauma of politics: a surgeon general's perspective. PMID- 24237916 TI - The Ask-Advise-Connect approach for smokers in a safety net healthcare system: a group-randomized trial. AB - BACKGROUND: Because smoking has a profound impact on socioeconomic disparities in illness and death, it is crucial that vulnerable populations of smokers be targeted with treatment. The U.S. Public Health Service recommends that all patients be asked about their smoking at every visit and that smokers be given brief advice to quit and referred to treatment. PURPOSE: Initiatives to facilitate these practices include the 5A's (ask, advise, assess, assist, arrange) and Ask-Advise-Refer (AAR). Unfortunately, primary care referrals are low, and most smokers referred fail to enroll. This study evaluated the efficacy of the Ask-Advise-Connect (AAC) approach to linking smokers with treatment in a large, safety net public healthcare system. DESIGN: The study design was a pair matched group-randomized trial with two treatment arms. SETTING/PARTICIPANTS: Ten safety net clinics in Houston TX. INTERVENTION: Clinics were randomized to AAC (n=5; intervention) or AAR (n=5; control). Licensed vocational nurses (LVNs) were trained to assess and record the smoking status of all patients at all visits in the electronic health record. Smokers were given brief advice to quit. In AAC, the names and phone numbers of smokers who agreed to be connected were sent electronically to the Texas quitline daily, and patients were proactively called by the quitline within 48 hours. In AAR, smokers were offered a quitline referral card and encouraged to call on their own. Data were collected between June 2010 and March 2012 and analyzed in 2012. MAIN OUTCOME MEASURES: The primary outcome was impact, defined here as the proportion of identified smokers that enrolled in treatment. RESULTS: The impact (proportion of identified smokers who enrolled in treatment) of AAC (14.7%) was significantly greater than the impact of AAR (0.5%), t(4)=14.61, p=0.0001, OR=32.10 (95% CI=16.60, 62.06). CONCLUSIONS: The AAC approach to aiding smoking cessation has tremendous potential to reduce tobacco-related health disparities. PMID- 24237918 TI - A partnership of two U.S. research networks to improve public health. PMID- 24237919 TI - Public health research implementation and translation: evidence from practice based research networks. AB - BACKGROUND: Research on how best to deliver efficacious public health strategies in heterogeneous community and organizational contexts remains limited. Such studies require the active engagement of public health practice settings in the design, implementation, and translation of research. Practice-based research networks (PBRNs) provide mechanisms for research engagement, but until now they have not been tested in public health settings. PURPOSE: This study uses data from participants in 14 public health PBRNs and a national comparison group of public health agencies to study processes influencing the engagement of public health settings in research implementation and translation activities. METHODS: A cross-sectional network analysis survey was fielded with participants in public health PBRNs approximately 1 year after network formation (n=357) and with a nationally representative comparison group of U.S. local health departments not participating in PBRNs (n=625). Hierarchic regression models were used to estimate how organizational attributes and PBRN network structures influence engagement in research implementation and translation activities. Data were collected in 2010-2012 and analyzed in 2012. RESULTS: Among PBRN participants, both researchers and practice agencies reported high levels of engagement in research activities. Local public health agencies participating in PBRNs were two to three times more likely than nonparticipating agencies to engage in research implementation and translation activities (p<0.05). Participants in less densely connected PBRN networks and in more peripheral locations within these networks reported higher levels of research engagement, greater perceived benefits from engagement, and greater likelihood of continued participation. CONCLUSIONS: PBRN networks can serve as effective mechanisms for facilitating research implementation and translation among public health practice settings. PMID- 24237920 TI - Factors affecting evidence-based decision making in local health departments. AB - BACKGROUND: Data indicating the extent to which evidence-based decision making (EBDM) is used in local health departments (LHDs) are limited. PURPOSE: This study aims to determine use of decision-making processes by New York State LHD leaders and upper-level staff and identify facilitators and barriers to the use of EBDM in LHDs. METHODS: The New York Public Health Practice-Based Research Network implemented a mixed-methods study in 31 LHDs. There were 20 individual interviews; five small-group interviews (two or three participants each); and two focus groups (eight participants each) conducted with people who had decision making authority. Information was obtained about each person's background and position, decision-making responsibilities, how decisions are made within their LHD, knowledge and experience with EBDM, use of each step of the EBDM process, and barriers and facilitators to EBDM implementation. Data were collected from June to November 2010 and analyzed in 2011. RESULTS: Overall, participants supported EBDM and expressed a desire to increase their department's use of it. Although most people understood the concept, a relatively small number had substantial expertise and experience with its practice. Many indicated that they applied EBDM unevenly. Factors associated with use of EBDM included strong leadership; workforce capacity (number and skills); resources; funding and program mandates; political support; and access to data and program models suitable to community conditions. CONCLUSIONS: EBDM is used inconsistently in LHDs in New York. Despite knowledge and interest among LHD leadership, the LHD capacity, resources, appropriate programming, and other issues serve as impediments to EBDM and optimal implementation of evidence-based strategies. PMID- 24237921 TI - Local public health resource allocation: limited choices and strategic decisions. AB - BACKGROUND: Local health department leaders are expected to improve the health of their populations as they "use and contribute to" the evidence base for practice, but effectively providing and utilizing data and evidence for local public health decision making has proven difficult. PURPOSE: This study was conducted in 2011 and initiated by Washington State's public health practice-based research network to identify factors influencing local resource allocation and programmatic decisions among public health leaders facing severe funding losses. METHODS: Quantitative data informed sampling for the collection of interview data. Qualitative methods were used to capture diverse insights of Washington State's local public health leaders in making decisions regarding resource allocation. RESULTS: Local decision-making authority was perceived as greatly restricted by what public health activities were legally mandated and the categoric nature of funding sources, even as some leaders exercised deliberate strategic approaches. One's workforce and board of health were also influential in making decisions regarding resource allocations. Challenges were expressed regarding making use of data and research evidence for decision making. Data were analyzed in 2011-2012. CONCLUSIONS: Programmatic mandates, funding restrictions, local stakeholders, and workforce capacity appear to trump factors such as research evidence and perceived community need in public health resource allocation. Study findings highlight tensions between the literature descriptions of what "should" influence decision making in local public health and the realities of practice. Advancements in practice-based research and evidence-based decision making, however, provide opportunities for strengthening the development of evidence and research translation for local decision making to maximize resources and promote effective service provision. PMID- 24237922 TI - Tax levy financing for local public health: fiscal allocation, effort, and capacity. AB - BACKGROUND: Local health departments (LHDs) rely on a wide variety of funding sources, and the level of financing is associated with both LHD performance in essential public health services and population health outcomes. Although it has been shown that funding sources vary across LHDs, there is no evidence regarding the relationship between fiscal allocation (local tax levy); fiscal effort (tax capacity); and fiscal capacity (community wealth). PURPOSE: The purpose of this study is to analyze local tax levy support for LHD funding. Three research questions are addressed: (1) What are tax levy trends in LHD fiscal allocation? (2) What is the role of tax levy in overall LHD financing? and (3) How do local community fiscal capacity and fiscal effort relate to LHD tax levy fiscal allocation? METHODS: This study focuses on 74 LHDs eligible for local tax levy funding in Minnesota. Funding and expenditure data for 5 years (2006 to 2010) were compiled from four governmental databases, including the Minnesota Department of Health, the State Auditor, the State Demographer, and the Metropolitan Council. Trends in various funding sources and expenditures are described for the time frame of interest. Data were analyzed in 2012. RESULTS: During the 2006-2010 time period, total average LHD per capita expenditures increased 13%, from $50.98 to $57.63. Although the overall tax levy increase in Minnesota was 25%, the local tax levy for public health increased 5.6% during the same period. There is a direct relationship between fiscal effort and LHD expenditures. CONCLUSIONS: Local funding reflects LHD community priorities and the relative importance in comparison to funding other local programs with tax dollars. In Minnesota, local tax levy support for local public health services is not keeping pace with local tax support for other local government services. These results raise important questions about the relationship between tax levy resource effort, resource allocation, and fiscal capacity as they relate to public health spending in local communities. PMID- 24237923 TI - Diabetes education: quality improvement interventions through health departments. AB - BACKGROUND: As the burden of diabetes continues to overwhelm the public health system, there is increased demand on local health departments (LHDs) to improve public health services. Quality improvement (QI) techniques have been shown to be an effective means to improve the delivery of services by LHDs. PURPOSE: To evaluate the extent to which the adoption of organizational QI strategies influences the delivery and outreach of diabetes self-management education (DSME) services provided by LHDs. METHODS: A change facilitation model that included QI team development and on-site QI training and facilitation was delivered to six LHDs that provide DSME, during 2010-2011. After training, each LHD developed and implemented a QI project to improve the outreach and delivery of DSME services. Pre- and post-intervention surveys were administered to evaluate the extent of change in DSME outreach and delivery. Data were analyzed in 2011. RESULTS: The number of individuals who completed an entire course of DSME increased by >100%, and 14% more diabetics attended DSME on a monthly basis. Half of LHDs reported receiving increased numbers of referrals per month, and 15% more healthcare providers referred diabetic patients to the LHD for DSME. CONCLUSIONS: Participation in Community Outreach and Change for Diabetes Management (COACH 4DM) led to improvements in the LHD QI infrastructure, and in the outreach and delivery of services to diabetic patients. The techniques used during COACH 4DM are applicable to a wide variety of contexts and may be an effective tool to improve the delivery of other clinical and community preventive services. PMID- 24237924 TI - The Team Science Toolkit: enhancing research collaboration through online knowledge sharing. PMID- 24237926 TI - Walking cadence and cardiovascular risk in children and adolescents: NHANES, 2005 2006. AB - BACKGROUND: Peak cadence (steps/minute) has been presented as an indicator of children's and adolescents' best natural daily effort. PURPOSE: The goal of the study was to determine the relationship between peak walking cadence and cardiovascular disease (CVD) risk factors in children and adolescents. METHODS: Data from the 2005-2006 National Health and Nutrition Examination Survey on accelerometer, high-density lipoprotein cholesterol, BMI, and blood pressure from 1817 children and adolescents (aged 8-18 years) were analyzed in 2012. Participants were stratified based on CVD risk factors (0, 1, and >=2) and age (8 11, 12-15, and 16-18 years). Age-specific trends were evaluated in peak 1-minute cadence (steps/minute recorded for the highest single minute in a day) and peak 30-minute and 60-minute cadence (average of the highest steps/minute recorded for the specified number of minutes, not necessarily consecutive) across strata. RESULTS: Across ascending age groups, peak 1-minute, 30-minute, and 60-minute cadence ranged from 123 to 111, 87 to 82, and 74 to 68 steps/minute, respectively. Peak 60-minute cadence means trended lower across groups of children with higher numbers of risk factors (p=0.02) in the age group 8-11 years; means similarly trended lower for all peak cadence indicators (all p for trend <0.01) in the age group 12-15 years; analogous trends were also significant in the age group 16-18 years. CONCLUSIONS: Results varied with age; however, children and adolescents who on average had higher peak cadence indicators tended to have fewer CVD risk factors. These cross-sectional data suggest that a simple indicator of best natural daily effort may play an important role in early progression of unfavorable cardiometabolic health. PMID- 24237925 TI - Trends and geographic patterns in drug-poisoning death rates in the U.S., 1999 2009. AB - BACKGROUND: Drug poisoning mortality has increased substantially in the U.S. over the past 3 decades. Previous studies have described state-level variation and urban-rural differences in drug-poisoning deaths, but variation at the county level has largely not been explored in part because crude county-level death rates are often highly unstable. PURPOSE: The goal of the study was to use small area estimation techniques to produce stable county-level estimates of age adjusted death rates (AADR) associated with drug poisoning for the U.S., 1999 2009, in order to examine geographic and temporal variation. METHODS: Population based observational study using data on 304,087 drug-poisoning deaths in the U.S. from the 1999-2009 National Vital Statistics Multiple Cause of Death Files (analyzed in 2012). Because of the zero-inflated and right-skewed distribution of drug-poisoning death rates, a two-stage modeling procedure was used in which the first stage modeled the probability of observing a death for a given county and year, and the second stage modeled the log-transformed drug-poisoning death rate given that a death occurred. Empirical Bayes estimates of county-level drug poisoning death rates were mapped to explore temporal and geographic variation. RESULTS: Only 3% of counties had drug-poisoning AADRs greater than ten per 100,000 per year in 1999-2000, compared to 54% in 2008-2009. Drug-poisoning AADRs grew by 394% in rural areas compared to 279% for large central metropolitan counties, but the highest drug-poisoning AADRs were observed in central metropolitan areas from 1999 to 2009. CONCLUSIONS: There was substantial geographic variation in drug-poisoning mortality across the U.S. PMID- 24237927 TI - Health literacy: an opinionated perspective. PMID- 24237928 TI - Strategies to prevent weight gain in adults: a systematic review. AB - CONTEXT: A Healthy People 2020 objective is to increase the prevalence of healthy weight adults in the U.S. A systematic review of the effectiveness and safety of strategies to prevent weight gain in adults was performed. EVIDENCE ACQUISITION: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and ClinicalTrials.gov were searched through June 2012. Two reviewers independently reviewed titles, abstracts, and articles. Trials and observational studies with at least 1 year of follow-up that reported on strategies to prevent weight gain or maintain weight were included. Data were abstracted on weight, adherence, safety, and quality-of-life outcomes. The quantity, quality, and consistency of the evidence were graded, with a focus on studies' risks of bias, consistency of results across studies, how directly the question of interest was addressed, and precision of results. A meaningful difference and a significant threshold (p<0.05) were used to identify effective strategies. Evidence was synthesized qualitatively. EVIDENCE SYNTHESIS: Twenty-two studies (11 trials and 11 observational studies) involving 480,142 participants were included. The strength of evidence is low for all strategies, but effective approaches may include low-fat diets, eating fewer meals prepared away from home, eating more fruits and vegetables, monitoring heart rate during exercise, and participation in group lifestyle sessions with reminder text messages. Safety and quality of life were rarely reported. CONCLUSIONS: Although the evidence is not strong, there may be effective strategies to prevent weight gain. PMID- 24237930 TI - Anesthetic considerations for neonates undergoing modified Blalock-Taussig shunt and variations. AB - The first Blalock-Taussig (BT) shunt was reported in 1944, and during the last 70 years, the procedure has evolved with the development of new materials and devices, and surgical approaches. It has, however, remained central to the palliation of neonates with complex congenital heart disease. The indications have expanded from the original aim of alleviating cyanosis and the pathophysiological results of chronic hypoxemia. They now include lesions with single ventricles, and rehabilitation of small pulmonary arteries. The physiology and hemodynamics of BT shunt circulations are very complex, and adverse hemodynamic events can be difficult to recognize. The consequences of shunt failure can be fatal, and the mortality (3-15%) and morbidity remain distressingly high even in the current era. Neonates undergoing BT shunt procedures or undergoing noncardiac surgery with this anatomy are challenging for the anesthesiologists to manage. There is a significant incidence of periprocedural cardiac arrest, often related to myocardial ischemia. A clear understanding of the anatomy and physiology is important. Any discussion of BT shunt in the current era has to include consideration of hypoplastic left heart syndrome and 'single ventricle' physiology. PMID- 24237929 TI - Topical diltiazem before transrectal ultrasonography-guided biopsy of the prostate: a randomized controlled trial. AB - BACKGROUND: Injection of local anaesthetic agents around the prostatic nerve bundles during transrectal ultrasonography (TRUS) biopsy of the prostate has shown to reduce the pain associated with the procedure. It has been shown that some of the discomfort associated with the procedure is secondary to spasm of the anal sphincter. Topical diltiazem can relax the anal sphincter. Our aim was to evaluate the use of topical diltiazem cream as an adjunct to periprostatic nerve block in reducing pain associated with TRUS-guided prostatic biopsy. METHOD: Between September 2009 and September 2010, 114 patients were enrolled in the trial (from two centres). Patients undergoing TRUS biopsy of prostate were randomized into diltiazem and placebo groups. Patients were asked to fill out a questionnaire at the end of the procedure. The questionnaire enquired about discomfort associated with various parts of the procedure using a 10-cm visual analogue scale (VAS). RESULTS: For discomfort due to the presence of the probe, pain during the biopsy and overall pain prior to leaving the department, mean VAS was higher for the placebo group, but the difference was not statistically significant. CONCLUSION: Diltiazem cream has a better side effect profile than glyceryl trinitrate cream and is better tolerated. Although we have demonstrated trends favouring diltiazem use as an adjunct to local anaesthetic in TRUS biopsy of the prostate, this did not reach a statistically significant level. The pain scores associated with TRUS biopsy in our cohort were lower than those in the published literature. This phenomenon might have contributed to the results observed in this trial. PMID- 24237931 TI - Enhancing person-centred communication in NICU: a comparative thematic analysis. AB - AIMS AND OBJECTIVES: Aims of this article were (a) to explore how parents of premature infants experience guided family-centred care (GFCC), and (b) to compare how parents receiving GFCC versus standard care (SC) describe nurse parent communication in the neonatal intensive care unit. BACKGROUND: Family centred care (FCC) is acknowledged as fundamental to supporting parents of premature infants, and communication is central to this practice. Accordingly, nurses need good communication skills. GFCC is an intervention developed to improve nurse-parent communication in the neonatal intensive care unit. This intervention helps nurses to realize person-centred communication as an approach to optimize contemporary practice. DESIGN: Our qualitative study had a descriptive and comparative design using semi-structured interviews to explore the parent's experience of GFCC. METHODS: We conducted 10 dyad interviews with parents (n = 20) and two individual interviews with mothers of premature infants (n = 2). Parents in the intervention group versus SC group were 13 versus 9. Thematic analysis was applied. FINDINGS: GFCC was generally experienced as supportive. Three interrelated themes were identified that illustrated how the intervention helped parents cope as persons, parents and couples: (a) discovering and expressing emotions, (b) reaching a deeper level of communication, and (c) obtaining mutual understanding. In contrast, SC communication was more superficial and less structured. Factors such as inaccessibility of nurses, inability to ask for assistance and parent popularity impaired successful communication. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Our study suggested that compared to SC, GFCC provided structured delivery of supportive communication between nurses and parents of premature infants. The intervention promoted the discovery of the parents' individual preferences and concerns, which enabled more focused communication, and set the stage for better nurse-parent and parent parent understanding. We recommend GFCC as a method to improve communication in the neonatal intensive care unit. PMID- 24237932 TI - Identification of the IGF1/PI3K/NF kappaB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer. AB - BACKGROUND: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. METHODS: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group. RESULTS: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF kappaB/ERK gene signalling networks. CONCLUSIONS: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our results provide a pathway context for further experimental validations, and the findings are a significant step towards future therapeutic interventions. PMID- 24237933 TI - Biomechanical comparison of menisci from different species and artificial constructs. AB - BACKGROUND: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e.g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3). METHODS: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T tests were used to compare the biomechanical parameters of all samples. Significance level was set at p < 0.05. RESULTS: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p < 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm +/- 1.87, cycle 1; ovine: 11.24 N/mm +/- 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N +/- 0.63, cycle 1 vs. ovine 3.24 N +/- 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92% +/- 0.63, cycle 1 vs. 18.72% +/- 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs -as hypothesized- revealed statistically significant inferior biomechanical properties. CONCLUSIONS: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing. PMID- 24237934 TI - Enhanced expression of the central survival of motor neuron (SMN) protein during the pathogenesis of osteoarthritis. AB - The identification of new components implicated in the pathogenesis of osteoarthritis (OA) might improve our understanding of the disease process. Here, we investigated the levels of the survival of motor neuron (SMN) expression in OA cartilage considering the fundamental role of the SMN protein in cell survival and its involvement in other stress-associated pathologies. We report that SMN expression is up-regulated in human OA compared with normal cartilage, showing a strong correlation with the disease severity, a result confirmed in vivo in an experimental model of the disease. We further show that the prominent inflammatory cytokines (IL-1beta, TNF-alpha) are critical inducers of SMN expression. This is in marked contrast with the reported impaired levels of SMN in spinal muscular atrophy, a single inherited neuromuscular disorder characterized by mutations in the smn gene whereas OA is a complex disease with multiple aetiologies. While the precise functions of SMN during OA remain to be elucidated, the conclusions of this study shed light on a novel pathophysiological pathway involved in the progression of OA, potentially offering new targets for therapy. PMID- 24237935 TI - Comment on 'Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades'. PMID- 24237938 TI - The evolving role of nurses in primary care medical settings. AB - The role of nurses in primary care is understudied. The purpose of this study was to describe the current registered nurse (RN) role in three Primary Care Networks (PCNs) in western Canada and to identify opportunities for optimal utilization of RNs in these settings. Case study methodology included interviews and document review. Although the RN role evolved during the study, most RNs focused on chronic disease management. Role ambiguity was evident between nurses and with interprofessional team members. Relationships of RNs to other providers, particularly physicians, impacted the enactment of the nursing role. Other barriers to role enactment included physician fee-for-service remuneration, management structures and processes, lack of access to electronic medical records and lack of previous opportunities to apply primary health-care education in the practice setting. Further work is needed to optimize the RN role in primary care to ensure maximum impact for patients, providers and the health system overall. PMID- 24237937 TI - Effectiveness of an intervention for prevention and treatment of burnout in primary health care professionals. AB - BACKGROUND: Burnout syndrome is an important health problem that affects many professionals and must be addressed globally, with both organizational measures and personal interventions. Burnout of health professionals can be prevented in order to avoid personal, familial, and social consequences, as well as repercussions for patients. METHODS/DESIGN: This work describes a protocol for a controlled, pragmatic, randomized clinical trial in 2 parallel groups: intervention and control. All health professionals from 7 health care centers will form the intervention group, and all health professionals from 7 different health care centers will form the control group. The intervention group will receive 16 hours of training at their work place. The Maslach's burnout inventory, the Cuestionario de Desgaste Profesional Medico or the Cuestionario de Desgaste Profesional de Enfermeria, and the 28-item Goldberg's General Health Questionnaire, validated for our setting, will be used as measurement tools. Change in the average scores from the Maslach's burnout inventory emotional exhaustion scale will be compared between the intervention and control groups, measured as intention-to-treat, and the intervention will be considered effective if a minimum decrease of 20% is achieved. DISCUSSION: Due to the deleterious consequences of burnout syndrome for people suffering from it and for the organization where they work, it is necessary to evaluate the effectiveness of certain interventions for its prevention. Organizational measures are important for preventing burnout syndrome, but so is providing professionals with coping strategies, as this group intervention intends to do. TRIAL REGISTRATION: ClinicalTrials.gov processed this record on June 10, 2013. ClinicalTrials.gov Identifier: NCT01870154. PMID- 24237936 TI - Dual-acting stapled peptides target both HIV-1 entry and assembly. AB - BACKGROUND: Previously, we reported the conversion of the 12-mer linear and cell impermeable peptide CAI to a cell-penetrating peptide NYAD-1 by using an i,i + 4 hydrocarbon stapling technique and confirmed its binding to the C-terminal domain (CTD) of the HIV-1 capsid (CA) protein with an improved affinity (K(d) ~ 1 MUM) compared to CAI (K(d) ~ 15 MUM). NYAD-1 disrupts the formation of both immature- and mature-like virus particles in in vitro and cell-based assembly assays. In addition, it displays potent anti-HIV-1 activity in cell culture against a range of laboratory-adapted and primary HIV-1 isolates. RESULTS: In this report, we expanded the study to i,i + 7 hydrocarbon-stapled peptides to delineate their mechanism of action and antiviral activity. We identified three potent inhibitors, NYAD-36, -66 and -67, which showed strong binding to CA in NMR and isothermal titration calorimetry (ITC) studies and disrupted the formation of mature-like particles. They showed typical alpha-helical structures and penetrated cells; however, the cell penetration was not as efficient as observed with the i,i + 4 peptides. Unlike NYAD-1, the i,i + 7 peptides did not have any effect on virus release; however, they impaired Gag precursor processing. HIV-1 particles produced in the presence of these peptides displayed impaired infectivity. Consistent with an effect on virus entry, selection for viral resistance led to the emergence of two mutations in the gp120 subunit of the viral envelope (Env) glycoprotein, V120Q and A327P, located in the conserved region 1 (C1) and the base of the V3 loop, respectively. CONCLUSION: The i,i + 7 stapled peptides derived from CAI unexpectedly target both CA and the V3 loop of gp120. This dual-targeted activity is dependent on their ability to penetrate cells as well as their net charge. This mechanistic revelation will be useful in further modifying these peptides as potent anti-HIV-1 agents. PMID- 24237939 TI - Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis. AB - AIMS: Indirect evidence from randomized controlled trials (RCTs) was used to estimate the effect of dapagliflozin, a new agent with a novel mechanism of action (SGLT-2 inhibition), relative to other anti-diabetes therapies after 1 year of treatment. METHODS: A systematic literature review and Bayesian network meta-analysis (NMA) of RCTs involving anti-diabetes treatments added to metformin were conducted. RCTs enrolling subjects with type 2 diabetes inadequately controlled on metformin monotherapy were included. Comparators included dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), sulphonylureas, glucagon-like peptide-1 (GLP-1) analogues and dapagliflozin. Outcomes of interest were mean change from baseline HbA1c, weight and systolic blood pressure, and incidence of hypoglycaemia. RESULTS: From 4270 abstracts, six RCTs were included in the primary analysis; no RCTs involving GLP-1 analogues met primary inclusion criteria. All RCTs were actively controlled with sulphonylureas. The mean change in HbA1c from baseline was similar across comparators. The treatment effect (95% credible interval) of dapagliflozin on HbA1c was -0.08% (-0.25, 0.10) relative to DPP-4 inhibitors, -0.02% (-0.24, 0.21) relative to TZDs and 0.00% (-0.16, 0.16) relative to sulphonylureas. Non sulphonylureas showed significantly lower risk of hypoglycaemia relative to sulphonylureas. Dapagliflozin had a significant effect on weight change: the relative difference was -2.74 kg (-5.35, -0.10) compared with DPP-4 inhibitors, and -4.67 kg (-7.03, -2.35) compared with sulphonylureas. Systolic blood pressure was not meta-analysed due to infrequent reporting. CONCLUSION: Compared with DPP 4 inhibitors, TZDs and sulphonylureas, dapagliflozin offers similar HbA1c control after 1 year, with similar or reduced risk of hypoglycaemia and the additional benefit of weight loss, when added to metformin. PMID- 24237941 TI - A comparative study of the anatomy of adipose tissue in areas with and without raised lesions of cellulite using magnetic resonance imaging. AB - BACKGROUND: Cellulite is considered a noninflammatory phenomenon characterized by alterations to the skin surface, with depressed and raised lesions. Few studies have evaluated subcutaneous fat in patients with cellulite, and there is no information about the anatomy of raised lesions. METHODS: Sixty women with raised cellulite lesions were evaluated using magnetic resonance imaging (MRI). Cellulite grade was evaluated using the Cellulite Severity Scale (CSS). Raised cellulite lesions were marked and compared with control areas on the opposite side of the body (buttocks, abdomen, and upper thighs). RESULTS: Mean age was 39.3 +/- 11.0 years and average body mass index (BMI) was 25.4 +/- 4.1 kg/m(2) . There were no differences between the raised lesions and the control areas in the anatomy of the fat lobes and their size. CSS scores were higher in older patients and in those with higher BMI. Patients with higher BMI had more fat lobes. CONCLUSIONS: The anatomy of subcutaneous fat was similar in raised and control areas for shape, size, and thickness. Higher CSS scores were found in older patients and those with higher BMI. PMID- 24237940 TI - Non-invasive hepatic biomarkers (ELF and CK18) in people with type 2 diabetes: the Edinburgh type 2 diabetes study. AB - BACKGROUND & AIMS: Type 2 diabetes is an established risk factor for the presence and progression of fatty liver. Little is known about the distributions and correlates of hepatic non-invasive biomarkers in community-based populations with diabetes, unselected for liver disease. We aimed to identify the distribution of, and metabolic risk factors associated with serum cytokeratin-18 (CK18) and the Enhanced Liver Fibrosis score (ELF), in a large, representative cohort of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study, ET2DS). METHODS: Nine hundred and thirty-nine ET2DS participants, aged 60-74 years underwent physical examination including ultrasound for assessment of liver fat. Representative subgroups were assessed for markers of chronic liver disease (CK18 and ELF). RESULTS: CK18 values ranged from 29-993 U/L (median 102, IQR 76-137 U/L) and ELF scores ranged from 6.9-11.6 (mean 8.9, SD 0.8). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres). CONCLUSIONS: We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much of the variation in biomarkers remained unexplained. Prospective studies are required to determine the extent to which CK18 and/or ELF predict the development of symptomatic liver disease and to identify additional risk factors which may influence the development of advanced liver disease in people with type 2 diabetes. PMID- 24237942 TI - 100 top-cited scientific papers in limb prosthetics. AB - Research has tremendously contributed to the developments in both practical and fundamental aspects of limb prosthetics. These advancements are reflected in scientific articles, particularly in the most cited papers. This article aimed to identify the 100 top-cited articles in the field of limb prosthetics and to investigate their main characteristics. Articles related to the field of limb prosthetics and published in the Web of Knowledge database of the Institute for Scientific Information (ISI) from the period of 1980 to 2012. The 100 most cited articles in limb prosthetics were selected based on the citation index report. All types of articles except for proceedings and letters were included in the study. The study design and level of evidence were determined using Sackett's initial rules of evidence. The level of evidence was categorized either as a systematic review or meta-analysis, randomized controlled trial, cohort study, case-control study, case series, expert opinion, or design and development. The top cited articles in prosthetics were published from 1980 to 2012 with a citation range of 11 to 90 times since publication. The mean citation rate was 24.43 (SD 16.7) times. Eighty-four percent of the articles were original publications and were most commonly prospective (76%) and case series studies (67%) that used human subjects (96%) providing level 4 evidence. Among the various fields, rehabilitation (47%), orthopedics (29%), and sport sciences (28%) were the most common fields of study. The study established that studies conducted in North America and were written in English had the highest citations. Top cited articles primarily dealt with lower limb prosthetics, specifically, on transtibial and transradial prosthetic limbs. Majority of the articles were experimental studies. PMID- 24237943 TI - Inferring protein-protein interaction complexes from immunoprecipitation data. AB - BACKGROUND: Protein-protein interactions in cells are widely explored using small scale experiments. However, the search for protein complexes and their interactions in data from high throughput experiments such as immunoprecipitation is still a challenge. We present "4N", a novel method for detecting protein complexes in such data. Our method is a heuristic algorithm based on Near Neighbor Network (3N) clustering. It is written in R, it is faster than model based methods, and has only a small number of tuning parameters. We explain the application of our new method to real immunoprecipitation results and two artificial datasets. We show that the method can infer protein complexes from protein immunoprecipitation datasets of different densities and sizes. FINDINGS: 4N was applied on the immunoprecipitation dataset that was presented by the authors of the original 3N in Cell 145:787-799, 2011. The test with our method shows that it can reproduce the original clustering results with fewer manually adapted parameters and, in addition, gives direct insight into the complex complex interactions. We also tested 4N on the human "Tip49a/b" dataset. We conclude that 4N can handle the contaminants and can correctly infer complexes from this very dense dataset. Further tests were performed on two artificial datasets of different sizes. We proved that the method predicts the reference complexes in the two artificial datasets with high accuracy, even when the number of samples is reduced. CONCLUSIONS: 4N has been implemented in R. We provide the sourcecode of 4N and a user-friendly toolbox including two example calculations. Biologists can use this 4N-toolbox even if they have a limited knowledge of R. There are only a few tuning parameters to set, and each of these parameters has a biological interpretation. The run times for medium scale datasets are in the order of minutes on a standard desktop PC. Large datasets can typically be analyzed within a few hours. PMID- 24237944 TI - Preventing post-ERCP pancreatitis. PMID- 24237945 TI - EUS-guided pancreatic duct drainage: ready for prime time? PMID- 24237946 TI - Not so NICE to be serrated. PMID- 24237947 TI - Enteral stents: from esophagus to colon. AB - Because of significant advances in endoscopic techniques and the development of high-quality stents, endoscopic enteral stent placement is increasingly being performed for the management of malignant GI obstruction. Palliative stenting is now routinely performed for malignant esophageal, gastric, duodenal, and colon obstruction. In addition to palliative indications, preoperative stenting in the colon may be performed as a bridge to surgery to achieve immediate decompression and convert an emergent surgery into an elective, 1-stage procedure.The realm of enteral stenting has recently expanded to include management of benign conditions such as leaks, fistulas, and benign strictures in the GI tract. Further research is required to study the use of enteral stents in benign conditions and to adequately compare endoscopic stent placement with surgical intervention. Promising new technologies such as biodegradable stents and drug-eluting stents also require further investigation. With continued innovation in endoscopic techniques and stenting devices, the field of enteral stenting is likely to expand further, with an increase in indications and improvement in outcomes. PMID- 24237948 TI - Novel method of stent insertion for malignant lower rectal obstruction with proximal releasing delivery system (with video). AB - BACKGROUND: Self-expandable metal stents are an alternative to preoperative and palliative colostomy for patients with malignant colorectal obstruction. However, self-expandable metal stent placement is considered unsuitable or contraindicated for patients with malignant lower rectal obstruction within 5 cm of the anal verge because the exposed stent portion can irritate the distal rectum and cause anal pain and a foreign body sensation. OBJECTIVE: To describe our experience with 6 patients with malignant lower rectal obstruction who underwent stent insertion with a proximal releasing delivery system (PRDS). DESIGN: Prospective clinical series outcome study. SETTING: A tertiary-care referral university hospital. PATIENTS: This study involved all patients at our center who had a malignant lower rectal obstruction within 5 cm of the anal verge caused by rectal cancer and bladder cancer. INTERVENTION: Uncovered stent with the PRDS with endoscopic and fluoroscopic guidance. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rate, adverse event rate, and stent migration rate. RESULTS: All stents were placed at the expected location. Technical and clinical success rates were 100%. Two patients reported anal pain, which was controlled with analgesics. One case of tumor ingrowth occurred after 5 months and was treated with reinsertion of a stent with the PRDS. After stent insertion, the patients received chemotherapy, chemoradiotherapy, or conservative care. LIMITATIONS: Small number of patients and no comparison group. Further prospective, randomized, controlled trials are needed. CONCLUSIONS: Uncovered stent insertion with the PRDS is a feasible, safe, and effective treatment for the patient with malignant lower rectal obstruction within 5 cm from the anal verge. PMID- 24237949 TI - Novel EUS-guided gastrojejunostomy technique using a new double-balloon enteric tube and lumen-apposing metal stent (with videos). AB - BACKGROUND: Surgical gastrojejunostomy is associated with relatively high morbidity and mortality rates. However, current experimental EUS-guided gastrojejunostomy information is limited. OBJECTIVE: To evaluate a novel EUS guided gastrojejunostomy technique using a new enteric balloon and lumen-apposing metal stent. DESIGN: Animal experiment. SETTING: Animal laboratory at a referral center. SUBJECTS AND INTERVENTIONS: In 5 pigs, gastrojejunostomies were created under EUS guidance. Fully covered lumen-apposing stents were placed between the stomach and the jejunum. MAIN OUTCOME MEASUREMENTS: Technical success and adverse events of EUS-guided gastrojejunostomy. RESULTS: All stents, with 1 exception, were successfully deployed without any adverse events. The mean time to stent placement was 44.2 minutes (range 28-64 minutes). All animals showed normal eating behavior without signs of infection for 1 month after the procedure. Endoscopic imaging of the stomach site showed the stent to be patent and stable, without dislodgment, in all of the pigs. Necropsy showed complete adhesion between the stomach and the jejunum wall. LIMITATIONS: Pilot study. CONCLUSIONS: Creation of an EUS-guided gastrojejunostomy by using a novel enteric balloon and metal stent appears to be promising as a minimally invasive treatment. PMID- 24237950 TI - Endoscopic submucosal tunnel dissection: the space between. PMID- 24237951 TI - Endoscopic appearance of duodenal mucosa in GI leishmaniasis. PMID- 24237952 TI - A technique for skin-level gastrostomy tube placement after gastrostomy tube dislodgement. PMID- 24237953 TI - Response. PMID- 24237954 TI - Cyanoacrylate injection to treat recurrent bleeding from Dieulafoy's lesion. PMID- 24237955 TI - Prevalence and management of post-transplant anemia in long-term follow-up of Chinese kidney transplant recipients: a single-center report. AB - BACKGROUND: Post-transplant anemia (PTA) has long been a less-recognized complication in kidney transplant recipients, and its prevalence also tends to be underestimated. This study sought to evaluate the prevalence, management, and risk factors of PTA from a group of long-term follow-up Chinese kidney transplant recipients. METHODS: One hundred and fifty-four adult kidney transplant recipients were followed up at Fuzhou General Hospital, China, and retrospectively studied. RESULTS: PTA prevalence at transplant and at 5-yearly time points after transplantation were 45.5%, 10.7%, 9.6%, 14.8%, 13.5%, and 19.6%, respectively. Overall, 38.3% of patients had been anemic at least once during the follow-up period, and 42% of these patients had recurrent anemia. Correlation analysis indicated that hemoglobin levels were associated with graft function. No correlations between anemia and age, gender, immunosuppressive regimens, or antihypertensive agents were observed. Binary logistic regression analysis suggested that serum creatinine and blood urea nitrogen were associated with the diagnosis of anemia at 1 year post-transplant. At 5 years post transplant, only serum creatinine concentrations correlated with anemia. Although iron drugs are frequently used, erythropoietin was rarely administered in those anemic patients suffering poor graft function that necessitated such therapies. CONCLUSIONS: The prevalence of PTA is noticeably high, and impaired kidney graft function seemed to be the major risk factor for anemia. There is an urgent need to improve current PTA management and to establish modified guidelines for this common complication in kidney transplant recipients. PMID- 24237956 TI - Contemporary issues in nursing: patient safety, decision-making and social support in challenging economic times. PMID- 24237957 TI - Testing the reliability of the Fall Risk Screening Tool in an elderly ambulatory population. AB - AIM: To identify and test the reliability of a fall risk screening tool in an ambulatory outpatient clinic. BACKGROUND: The Fall Risk Screening Tool (Albert Lea Medical Center, MN, USA) was scripted for an interview format. METHOD: Two interviewers separately screened a convenience sample of 111 patients (age >= 65 years) in an ambulatory outpatient clinic in a northeastern US city. RESULT: The interviewers' scoring of fall risk categories was similar. There was good internal consistency (Cronbach's alpha = 0.834-0.889) and inter-rater reliability [intra-class correlation coefficients (ICC) = 0.824-0.881] for total, Risk Factor and Client's Health Status subscales. The Physical Environment scores indicated acceptable internal consistency (Cronbach's alpha = 0.742) and adequate reliability (ICC = 0.688). Two Physical Environment items (furniture and medical equipment condition) had low reliabilities [Kappa (K) = 0.323, P = 0.08; K = 0.078, P = 0.648), respectively. CONCLUSION: The scripted Fall Risk Screening Tool demonstrated good reliability in this sample. Rewording two Physical Environment items will be considered. IMPLICATIONS FOR NURSING MANAGEMENT: A reliable instrument such as the scripted Fall Risk Screening Tool provides a standardised assessment for identifying high fall risk patients. This tool is especially useful because it assesses personal, behavioural and environmental factors specific to community-dwelling patients; the interview format also facilitates patient-provider interaction. PMID- 24237958 TI - Family-paid caregivers in hospital health care in China. AB - AIM: The aims of this study were to identify the attitudes and perceptions of nurses towards family-paid caregivers, to examine the roles of caregivers in hospital bedside nursing care and to describe the supervision of family-paid caregivers by nurses. BACKGROUND: The inadequacy of nurse staffing and the Chinese tradition emphasising family responsibility have established family-paid caregivers as an important workforce for inpatient bedside nursing care in China. DESIGN: This was a descriptive study combining qualitative interviews with a quantitative cross-sectional questionnaire survey. METHODS: Six nurses were interviewed and 209 family-paid caregivers were surveyed. RESULTS: According to the respondents, patients relied on the caregivers to receive assistance and care during hospitalization and family-paid caregivers were involved in most of the bedside nursing care. CONCLUSIONS: The heavy workload of nurses and staffing inadequacy have led to a severe need for caregivers to provide bedside nursing care within hospitals in China. The roles of family-paid caregivers need to be defined and closely monitored. IMPLICATIONS FOR NURSING MANAGEMENT: Proper management of the caregivers should be strengthened and the hospital nursing workforce encouraged to take over bedside nursing care as essential strategies for improving nursing care quality and the patients' satisfaction with the hospitals. PMID- 24237959 TI - Letter to the editor: the role of participatory leadership in enhancing EBN. PMID- 24237960 TI - Letter to the editor: the impact of leadership styles on nurses' satisfaction. PMID- 24237961 TI - Coagulation and the surgical neonate. AB - Both coagulopathy and abnormal thrombosis can complicate the anesthetic and surgical management of neonatal patients; however, the patterns of bleeding and thrombosis in neonates differ from those in adults or older children. Severe coagulopathic bleeding most commonly occurs during heart surgery and almost certainly contributes to morbidity and mortality in this population. Such severe bleeding is rare during other surgery; the exception is babies presenting to the operating room with established coagulopathy secondary to severe sepsis. Alternatively, pathological thrombosis will mainly occur in association with indwelling vascular access devices or surgically created vascular shunts. There are important differences between the coagulation system in neonates and older patients. The implication of this is that therapies established in other patient groups will not be optimal for neonates without adaptation. While evidence from high-quality clinical trials is rarely available, an understanding of how coagulation in neonates differs can help to guide practice. This review will discuss important differences between the coagulation system of neonates and older patients and how these relate to newer models of coagulation. The emphasis will be on issues likely to impact on perioperative care. In particular, the management of severe bleeding, the manipulation of coagulation during heart surgery, and the management of coagulopathy in septic neonates will be discussed in detail. PMID- 24237962 TI - The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. AB - Irisin was first identified as a peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) dependent myokine with the potential to induce murine brown-fat-like development of white adipose tissue. In humans, the regulatory effect of training on muscle FNDC5 mRNA expression and subsequently irisin levels in plasma is more controversial. We recruited 26 inactive men (13 normoglycaemic and normal weight, controls; and 13 slightly hyperglycaemic and overweight, pre-diabetes group) aged 40-65 years for a 12-week intervention of combined endurance and strength training with four sessions of training per week. Before and after the 12-week intervention period, participants were exposed to an acute endurance workload of 45 min at 70% of VO(2max), and muscle biopsies were taken prior to and after exercise. Skeletal muscle mRNA for PGC1A and FNDC5 correlated and both PGC1A and FNDC5 mRNA levels increased after 12 weeks of training in both control and pre-diabetes subjects. Circulating irisin was reduced in response to 12 weeks of training, and was increased acutely (~1.2 fold) just after acute exercise. Plasma concentration of irisin was higher in pre diabetes subjects compared with controls. There was little effect of 12 weeks of training on selected browning genes in subcutaneous adipose tissue. UCP1 mRNA did not correlate with FNDC5 expression in subcutaneous adipose tissue or skeletal muscle or with irisin levels in plasma. We observed no enhancing effect of long term training on circulating irisin levels, and little or no effect of training on browning of subcutaneous white adipose tissue in humans. PMID- 24237963 TI - Wide QRS complex tachycardia in a patient with a biventricular implantable cardioverter defibrillator: what is the mechanism? PMID- 24237964 TI - Dispersal, landscape and travelling waves in cyclic vole populations. AB - Travelling waves (TW) are among the most striking ecological phenomena emerging in oscillating populations. Despite much theory, understanding how real-world TW arise remains a challenge for ecology. Herein, we analyse 16-year time series of cyclic vole populations collected at 314 localities covering 2500 km2 in France. We found evidence for a linear front TW spreading at a speed of 7.4 km year(-1) along a north-west/south-east direction and radiating away from a major landscape discontinuity as predicted by recent theory. The spatial signature of vole dispersal was assessed using genetic data collected at 14 localities. Both data sets were handled using similar autocorrelation approaches. Our results revealed a remarkable congruence of the spatial extent and direction of anisotropy of both demographic and genetic structures. Our results constitute the first empirical evidence that effective dispersal is limited in the direction of TW while most of the individual exchanges occur along the wave front. PMID- 24237965 TI - Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats. AB - The surface marker profile of mesenchymal stromal cells (MSCs) suggests that they can escape detection by the immune system of an allogeneic host. This could be an optimal strategy for bone regeneration applications, where off-the-shelf cells could be implanted to heal bone defects. However, it is unknown how pre differentiation of MSCs to an osteogenic lineage, a means of improving bone formation, affects their immunogenicity. Using immunohistological techniques in a rat ectopic implantation model, we demonstrate that allogeneic osteoprogenitors mount a T cell- and B cell-mediated immune response resulting in an absence of in vivo bone formation. Suppression of the host immune response with daily administration of an immunosuppressant, FK506, is effective in preventing the immune attack on the allogeneic osteoprogenitors. In the immunosuppressed environment, the allogeneic osteoprogenitors are capable of generating bone in amounts similar to those of syngeneic cells. However, using osteoprogenitors from one of the allogeneic donors led to newly deposited bone that was attacked by the host immune system, despite the continued administration of the immunosuppressant. This suggests that, although using an immunosuppressant can potentially suppress the immune attack on the allogeneic cells, optimizing the dose of the immunosuppressant may be crucial to ensure bone formation within the allogeneic environment. Overall, allografts comprising osteoprogenitors derived from allogeneic MSCs have the potential to be used in bone regeneration applications. PMID- 24237967 TI - Variation in postpartum contraceptive method use: results from the Pregnancy Risk Assessment Monitoring System (PRAMS). AB - OBJECTIVE: The National Survey of Family Growth has been a primary data source for trends in US women's contraceptive use. However, national-level data may mask differences in contraceptive practice resulting from variation in local policies and norms. STUDY DESIGN: We used the Pregnancy Risk Assessment Monitoring System, a survey of women who are 2-4 months postpartum. Information on women's current method was available for 18 reporting areas from 2000 to 2009. Using the two most recent years of data, we computed the weighted proportion of women using specific contraceptive methods according to payment for delivery (Medicaid or private insurance) and examined differences across states. We used log binomial regression to assess trends in method use in 8 areas with consecutive years of data. RESULTS: Across states, there was a wide range of use of female sterilization (7.0-22.6%) and long-acting reversible contraception (LARC; 1.9 25.5%). Other methods, like vasectomy and the patch/ring, had a narrower range of use. Women with Medicaid-paid deliveries were more likely to report female sterilization, LARC and injectables as their method compared to women with private insurance. LARC use increased >=18% per year, while use of injectables and oral contraceptives declined by 2.5-10.6% annually. CONCLUSIONS: The correlation in method-specific prevalence within states suggests shared social and medical norms, while the larger variation across states may reflect both differences in norms and access to contraception for low-income women. Surveys of postpartum women, who are beginning a new segment of contraceptive use, may better capture emerging trends in US contraceptive method mix. IMPLICATIONS: There is considerable variation in contraceptive method use across states, which may result from differences in state policies and funding for family planning services, local medical norms surrounding contraceptive practice, and women's and couples' demand or preference for different methods. PMID- 24237968 TI - A comparison of alfaxalone and propofol on intraocular pressure in healthy dogs. AB - OBJECTIVE: To compare the effects of alfaxalone and propofol on intraocular (IOP) pressure in the canine eye. ANIMALS STUDIED: Twenty-three healthy adult dogs. PROCEDURES: Dogs were randomized to receive intravenous propofol (n = 11) or alfaxalone (n = 12) until loss of jaw tone, 20 min after intravenous premedication (acepromazine 0.02-0.03 mg/kg and hydromorphone 0.05-0.1 mg/kg). IOP was measured at baseline (BL), 20 min postpremedication (postpremed), loss of jaw tone (postinduct), and immediately following orotracheal intubation (postintub). Between- and within-treatment effects were analyzed with two-way and one-way repeated measures ANOVA with Bonferroni's post hoc test, respectively. P < 0.05 was considered significant. RESULTS: No significant IOP differences were detected between alfaxalone or propofol groups at any time point (P > 0.05). Propofol: IOP did not change between BL (15.5 +/- 2.7 mmHg) and postpremed (16.2 +/- 3.6 mmHg, P > 0.05), or postinduct (19.1 +/- 5.2 mmHg) and postintub (21.0 +/ 4.6 mmHg, P > 0.05), but differed significantly between BL and postinduct (P < 0.0001), and postintub (P < 0.0001). Alfaxalone: IOP did not change between BL (15.7 +/- 2.8 mmHg) and postpremed (15.3 +/- 4.1 mmHg, P > 0.05), or postinduct (19.2 +/- 4.9 mmHg) and postintub (20.5 +/- 4.5 mmHg, P > 0.05), but differed significantly between BL and postinduct (P < 0.01), and postintub (P < 0.0001). CONCLUSIONS: These data show a potentially clinically significant increase in IOP following induction with propofol or alfaxalone, but no difference between agents. PMID- 24237966 TI - Molecular adaptation of telomere associated genes in mammals. AB - BACKGROUND: Placental mammals display a huge range of life history traits, including size, longevity, metabolic rate and germ line generation time. Although a number of general trends have been proposed between these traits, there are exceptions that warrant further investigation. Species such as naked mole rat, human and certain bat species all exhibit extreme longevity with respect to body size. It has long been established that telomeres and telomere maintenance have a clear role in ageing but it has not yet been established whether there is evidence for adaptation in telomere maintenance proteins that could account for increased longevity in these species. RESULTS: Here we carry out a molecular investigation of selective pressure variation, specifically focusing on telomere associated genes across placental mammals. In general we observe a large number of instances of positive selection acting on telomere genes. Although these signatures of selection overall are not significantly correlated with either longevity or body size we do identify positive selection in the microbat species Myotis lucifugus in functionally important regions of the telomere maintenance genes DKC1 and TERT, and in naked mole rat in the DNA repair gene BRCA1. CONCLUSION: These results demonstrate the multifarious selective pressures acting across the mammal phylogeny driving lineage-specific adaptations of telomere associated genes. Our results show that regardless of the longevity of a species, these proteins have evolved under positive selection thereby removing increased longevity as the single selective force driving this rapid rate of evolution. However, evidence of molecular adaptations specific to naked mole rat and Myotis lucifugus highlight functionally significant regions in genes that may alter the way in which telomeres are regulated and maintained in these longer-lived species. PMID- 24237969 TI - Type 2 diabetes mellitus as a risk factor for intestinal resection in patients with superior mesenteric vein thrombosis. AB - BACKGROUND & AIMS: The most serious complication of acute mesenteric vein thrombosis (MVT) is acute intestinal ischaemia requiring intestinal resection or causing death. Risk factors for this complication are unknown. To identify risk factors for severe intestinal ischaemia leading to intestinal resection in patients with acute MVT. METHODS: We retrospectively analysed consecutive patients seen between 2002 and 2012 with acute MVT in 2 specialized units. Patients with cirrhosis were excluded. We compared patients who required intestinal resection to patients who did not. RESULTS: Among 57 patients, a local risk factor was identified in 14 (24%) patients, oral contraceptive use in 16 (29%), and at least one or more other systemic prothrombotic condition in 25 (44%). Five (9%) patients had diabetes mellitus (DM), 33 (58%) had overweight or obesity, 9 (18%) had hypertriglyceridemia and 10 (19%) had arterial hypertension. Eleven patients (19%) underwent intestinal resection. DM was significantly associated with intestinal resection (P = 0.02) while local factors or prothrombotic conditions were not. Computed tomography (CT) scans performed at diagnosis found that occlusion of second order radicles of the superior mesenteric vein was more frequently observed in patients who underwent intestinal resection (P = 0.009). CONCLUSIONS: In acute MVT, patients with underlying DM have an increased risk of requiring intestinal resection. Neither local factors nor systemic prothrombotic conditions are associated with intestinal resection. When CT scan shows the preservation of second order radicles of the superior mesenteric vein, the risk of severe resection is low. PMID- 24237970 TI - Primate lentiviral Nef proteins deregulate T-cell development by multiple mechanisms. AB - BACKGROUND: A nef gene is present in all primate lentiviral genomes and is important for high viral loads and progression to AIDS in human or experimental macaque hosts of HIV or SIV, respectively. In these hosts, infection of the thymus results in a decreased output of naive T cells that may contribute to the development of immunodeficiency. We have previously shown that HIV-1 subtype B Nef proteins can block human T-cell development. However, the underlying mechanism(s) and the conservation of this Nef function between different groups of HIV and SIV remained to be determined. RESULTS: We investigated whether reduction of thymic output is a conserved function of highly divergent lentiviral Nef proteins including those from both types of human immunodeficiency viruses (HIV-1 and HIV-2), their direct simian counterparts (SIVcpz, SIVgor and SIVsmm, respectively), and some additional SIV strains. We found that expression of most of these nef alleles in thymocyte progenitors impaired T-cell development and reduced thymic output. For HIV-1 Nef, binding to active p21 protein (Cdc42/Rac) activated kinase (PAK2) was a major determinant of this function. In contrast, selective disruption of PAK2 binding did not eliminate the effect on T-cell development of SIVmac239 Nef, as was shown by expressing mutants in a newly discovered PAK2 activating structural motif (PASM) constituted by residues I117, H121, T218 and Y221, as well as previously described mutants. Rather, down modulation of cell surface CD3 was sufficient for reduced thymic output by SIVmac Nef, while other functions of SIV Nefs contributed. CONCLUSIONS: Our results indicate that primate lentiviral Nef proteins impair development of thymocyte precursors into T cells in multiple ways. The interaction of HIV-1 Nef with active PAK2 by HIV-1 seem to be most detrimental, and downregulation of CD3 by HIV-2 and most SIV Nef proteins sufficient for reduced thymic output. Since the reduction of thymic output by Nef is a conserved property of divergent lentiviruses, it is likely to be relevant for peripheral T-cell depletion in poorly adapted primate lentiviral infections. PMID- 24237971 TI - Development of the hematopoietic system and disorders of hematopoiesis that present during infancy and early childhood. AB - This article reviews the ontogeny of hematopoiesis (embryonic/fetal/newborn phases) and its regulation and provides examples of the disorders of hematopoiesis that present in the newborn or infant and their pathophysiology. Many of these disorders are discussed in depth in other articles of this issue. PMID- 24237974 TI - Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC). AB - A complete blood cell count (CBC) is a frequent test sent to aid in the diagnostic evaluation of ill patients. Not uncommonly hematologic abnormalities may be the first sign of an underlying systemic disorder. The astute clinician needs to understand how systemic disease can affect the CBC to direct further diagnostic investigations. This article focuses on the 2 most common acquired anemias including iron deficiency and anemia of inflammation as well as disseminated intravascular coagulation. PMID- 24237972 TI - The inherited bone marrow failure syndromes. AB - Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and biochemistry is warranted for appropriate diagnosis and management of afflicted patients and to identify the physiology of the normal hematopoiesis and mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies, which include ribosome assembly and ribosomal RNA processing. The Fanconi anemia pathway has become interdigitated with the familial breast cancer syndromes. In this article, the diseases that account for most IBMFS diagnoses are analyzed. PMID- 24237973 TI - Acquired aplastic anemia in children. AB - This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder. PMID- 24237975 TI - Abnormalities of the erythrocyte membrane. AB - Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy. PMID- 24237977 TI - Thalassemias. AB - The thalassemia syndromes are hemoglobin disorders that result from significantly reduced or absent synthesis of either the alpha- or beta-globin chains. The result is a chronic hemolytic anemia with ineffective erythropoiesis and bone marrow overstimulation. This article reviews current diagnostic approaches, complications, and disease management of thalassemia. PMID- 24237978 TI - Evaluation and treatment of transfusional iron overload in children. AB - Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. PMID- 24237976 TI - Sickle cell disease in childhood: from newborn screening through transition to adult medical care. AB - Sickle cell disease (SCD) is the name for a group of related blood disorders caused by an abnormal hemoglobin molecule that polymerizes on deoxygenation. SCD affects the entire body, and the multisystem pathophysiology begins in infancy. Thanks to prognostic and therapeutic advancements, some forms of SCD-related morbidity are decreasing, such as overt stroke. Almost all children born with SCD in developed nations now live to adulthood, and lifelong multidisciplinary care is necessary. This article provides a broad overview of SCD in childhood, from newborn screening through transition to adult medical care. PMID- 24237979 TI - Developmental hemostasis: clinical implications from the fetus to the adolescent. AB - The coagulation system involves a dynamic group of procoagulation and anticoagulation proteins that appear early in fetal life and whose levels change throughout childhood and into the teenage years. This process is called developmental hemostasis. Developmental hemostasis creates unique challenges for clinicians affecting the diagnosis and treatment of coagulation disorders during early childhood. The objective of this review is to assist pediatricians in understanding the coagulation system in fetal life and childhood and to provide guidance for interpreting basic coagulation testing, which will result in an improved ability to diagnose and treat patients with hemostatic and thrombotic disorders. PMID- 24237980 TI - Inherited abnormalities of coagulation: hemophilia, von Willebrand disease, and beyond. AB - Bleeding disorders are broadly classified into primary and secondary hemostatic defects. Primary hemostatic disorders (disorders of platelets and von Willebrand factor) mainly result in mucocutaneous bleeding symptoms such as epistaxis, menorrhagia, petechiae, easy bruising, and bleeding after dental and surgical interventions. Secondary hemostatic disorders (congenital or acquired deficiencies of coagulation factors) typically manifest with delayed, deep bleeding into muscles and joints. This article provides a generalized overview of the pathophysiology, clinical manifestations, laboratory abnormalities, and molecular basis of inherited abnormalities of coagulation with a focus on hemophilia, von Willebrand disease, and rare inherited coagulation disorders. PMID- 24237981 TI - Pediatric thrombophilia. AB - Pediatric thrombosis and thrombophilia are increasingly recognized and studied. In this article, both the inherited and acquired factors for the development of thrombosis in neonates and children are categorized using the elements of Virchow's triad: stasis, hypercoagulable state, and vascular injury. The indications and rationale for performing thrombophilia testing are described. Also included are discussions on who, how, when, and why to test. Finally, recommendations for the use of contraceptives for adolescent females with a family history of thrombosis are outlined. PMID- 24237982 TI - Antithrombotic therapies: anticoagulation and thrombolysis. AB - Pediatric deep vein thrombosis is an increasingly recognized phenomenon, especially with advances in treatment and supportive care of critically ill children and with better diagnostic capabilities. High-quality evidence and uniform management guidelines for antithrombotic treatment, particularly thrombolytic therapy, remain limited. Optimal dosing, intensity and duration strategies for anticoagulation as well as thrombolytic regimens that maximize efficacy and safety need to be determined through well-designed clinical trials using use of a risk-stratified approach. PMID- 24237983 TI - Inherited disorders of platelet function. AB - Inherited platelet function disorders are of variable severity and unknown frequency and may be difficult to diagnose. Nevertheless, they are increasingly recognized as an important cause of bleeding in pediatrics, particularly in adolescent girls with menorrhagia, where they may be more common than von Willebrand disease. This article reviews the presentation of these disorders, summarizes the most common types of platelet function disorders, discusses the challenges in diagnostic testing, and details treatment and supportive care options. PMID- 24237984 TI - Diagnosis and management of autoimmune cytopenias in childhood. AB - The diagnosis and management of children with autoimmune cytopenias can be challenging. Children can present with immune-mediated destruction of a single cell lineage or multiple cell lineages, including platelets (immune thrombocytopenia [ITP]), erythrocytes (autoimmune hemolytic anemia), and neutrophils (autoimmune neutropenia). Immune-mediated destruction can be primary or secondary to a comorbid immunodeficiency, malignancy, rheumatologic condition, or lymphoproliferative disorder. Treatment options generally consist of nonspecific immune suppression or modulation. This nonspecific approach is changing as recent insights into disease biology have led to targeted therapies, including the use of thrombopoietin mimetics in ITP and sirolimus for cytopenias associated with autoimmune lymphoproliferative syndrome. PMID- 24237986 TI - Transfusion and hemovigilance in pediatrics. AB - Hemovigilance is an essential part of the transfusion process and is defined as surveillance procedures covering the whole transfusion chain, from collection of blood and its components, intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products and to prevent their occurrence or recurrence. The UK surveillance scheme has collected data for 16 years and is a model demonstrating how information on adverse incidents can be used to improve patient safety, influencing the management of donors and improved education and training for the many people involved in the transfusion process. PMID- 24237985 TI - HUS and TTP in Children. AB - This review describes the epidemiology, pathophysiology, presentation, clinical causes, treatment, and long-term prognosis of pediatric patients who present with thrombotic microangiopathy. The focus is on hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, the most common phenotypes of thrombotic microangiopathy. PMID- 24237987 TI - Blood banking/immunohematology: special relevance to pediatric patients. AB - Blood banking/immunohematology is an area of laboratory medicine that involves the preparation of blood and blood components for transfusion as well as the selection and monitoring of those components following transfusion. The preparation, modification, and indications of both traditional and newer products are described in this review, along with special considerations for neonates, patients undergoing hematopoietic stem cell transplantation, those with sickle cell disease, and others. Immunohematological techniques are critical in the provision of blood and blood products and are briefly discussed. PMID- 24237988 TI - Pediatric therapeutic apheresis: rationale and indications for plasmapheresis, cytapheresis, extracorporeal photopheresis, and LDL apheresis. AB - Apheresis refers to the removal of a component of the blood and is performed using a group of medical technologies in which peripheral blood is processed by an instrument that separates the various components. The selected component is isolated while the remainder is returned to the patient. The rationale behind therapeutic apheresis is to remove the pathogenic components from the circulation. Apheresis is also used for peripheral hematopoietic progenitor cell collection. The procedure can be safely performed in most children with modifications to account for smaller pediatric blood volumes. PMID- 24237989 TI - Pediatric hematology. PMID- 24237990 TI - Longitudinal evaluation of dementia care in German nursing homes: the "DemenzMonitor" study protocol. AB - BACKGROUND: In Germany, the number of people with dementia living in nursing homes is rapidly increasing. Providing adequate care for their special needs is a challenge for institutions and their staff members. Because of the growing number of people with dementia, changes to the conceptual orientation of nursing homes have occurred. These changes include specialized living arrangements and psychosocial interventions recommended for people with dementia. Until now, the provision of dementia care and its association to the residents' behavior and quality of life is not well investigated in Germany. The purpose of this study is to describe the provision of dementia care and to identify resident- as well as facility-related factors associated with residents behavior and quality of life. METHODS/DESIGN: The DemenzMonitor study is designed as a longitudinal study that is repeated annually. Data will be derived from a convenience sample consisting of nursing homes across Germany. For the data collection, three questionnaires have been developed that measure information on the level of the nursing home, the living units, and the residents. Data collection will be performed by staff members from the nursing homes. The data collection procedure will be supervised by a study coordinator who is trained by the research team. Data analysis will be performed on each data level using appropriate techniques for descriptions and comparisons as well as longitudinal regression analysis. DISCUSSION: The DemenzMonitor is the first study in Germany that assesses how dementia care is provided in nursing homes with respect to living arrangements and recommended interventions. This study links the acquired data with residents' outcome measurements, making it possible to evaluate different aspects and concepts of care. PMID- 24237992 TI - Chronic expanding hematoma in the retroperitoneal space: a case report. AB - BACKGROUND: Chronic expanding hematoma is a rare condition that develops after surgery, trauma, or injury. It can also develop at any location in the body in the absence of trauma. Clinical findings and various diagnostic imaging modalities can aid in the differential diagnosis of this condition. In general, hematomas are naturally reabsorbed and rarely cause serious problems. However, hematomas that develop slowly without a history of trauma, surgery, or bleeding disorders could be difficult to differentiate from soft tissue neoplasms. In the present case, we describe a patient, without any history or physical evidence of trauma, who exhibited a large chronic expanding hematoma in the retroperitoneal space that resulted in hydronephrosis because of the pressure exerted on the left ureter. CASE PRESENTATION: A 69-year-old man presented to our hospital with a swollen lesion in the left flank. A mass, 19 cm in diameter, was detected in the retroperitoneal space by computed tomography. We suspected the presence of a chronic expanding hematoma, soft tissue tumor, or left renal artery aneurysm. Surgical treatment was performed. However, postoperative histopathological examination indicated that the mass was a nonmalignant chronic expanding hematoma. No recurrence was observed during a 2-year follow-up period. CONCLUSION: In patients without a history of trauma who present slowly growing masses, the differential diagnosis should include chronic expanding hematoma in addition to cysts and soft tissue tumors. Moreover, the use of magnetic resonance imaging and computed tomography is essential to differentiate between chronic expanding hematoma and soft tissue tumors. PMID- 24237993 TI - Trace metal enrichments in nearshore sediments and accumulation in mussels (Modiolus capax) along the eastern coast of Baja California, Mexico: environmental status in 1995. AB - The biogeochemistry of trace metals in nearshore sediments and mussel was studied at 15 stations along a 1000 km long transect paralleling the west coast of the Gulf of California (GOC). Total trace metal (Me) and enrichment factor (EF(Me)) values in sediments were low due to negligible anthropogenic influence in the region. Past copper mining, however, near Santa Rosalia caused concentrations of Pb, Mn, Co, Zn and Cu which were 10-3.3*10(3) times greater than the average for the rest of the transect. Mussels also showed relatively high trace metal concentrations at the Santa Rosalia stations, but the variability in the spatial distribution was low and had undefined trends. Our results show that, with the exception of Co and Cu, the contamination caused by the copper mine affected sediments to a greater extent than mussels. PMID- 24237991 TI - Heterogeneous echogenicity of the underlying thyroid parenchyma: how does this affect the analysis of a thyroid nodule? AB - BACKGROUND: Heterogeneous echogenicity of the thyroid gland has been associated with diffuse thyroid disease and benign and malignant nodules can coexist with diffuse thyroid disease. Underlying heterogeneous echogenicity might make it difficult to differentiate between benign and malignant nodules on US. Thus, the aim of this study was to evaluate the influence of underlying thyroid echogenicity on diagnosis of thyroid malignancies using US. METHODS: A total of 1,373 patients who underwent US-guided fine needle aspiration of 1,449 thyroid nodules from June 2009 to August 2009 were included. The diagnostic performance of US assessment for thyroid nodules was calculated and compared according to underlying thyroid echogenicity. The diagnostic performance of US assessments in the diagnosis of thyroid malignancy according to the underlying parenchymal echogenicity was compared using a logistic regression with the GEE (generalized estimating equation) method. Each US feature of malignant and benign thyroid nodules was analyzed according to underlying echogenicity to evaluate which feature affected the final diagnosis. RESULTS: Among the 1,449 nodules, 325 (22.4%) were malignant and 1,124 (77.6%) were benign. Thyroid glands with heterogeneous echogenicity showed significantly lower specificity, PPV, and accuracy compared to thyroid glands with homogeneous echogenicity, 76.3% to 83.7%, 48.7% to 60.9%, and 77.6% to 84.4%, respectively (P=0.009, 0.02 and 0.005, respectively). In benign thyroid nodules, microlobulated or irregular margins were more frequently seen in thyroid glands with heterogeneous echogenicity than in those with homogenous echogenicity (P<0.001). CONCLUSION: Heterogeneous echogenicity of the thyroid gland significantly lowers the specificity, PPV, and accuracy of US in the differentiation of thyroid nodules. Therefore, caution is required during evaluation of thyroid nodules detected in thyroid parenchyma showing heterogeneous echogenicity. PMID- 24237994 TI - Persistent organic pollutants in benthic and pelagic organisms off Adelie Land, Antarctica. AB - The concentrations of polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), pentachlorobenzene (PeCB) and polybrominated diphenylethers (PBDE) were described in benthic and pelagic species collected off Adelie Land, Antarctica. Strong differences were observed among species, with reduced PeCB and HCB levels in benthic species, and elevated PCB levels in the Antarctic yellowbelly rockcod, the Antarctic sea urchin and the snow petrel. Lower-chlorinated congeners were predominant in krill; penta-PCBs in benthic organisms; hexa- and hepta-PCBs in seabirds and cryopelagic fish. This segregation may result from sedimentation process, specific accumulation and excretion, and/or biotransformation processes. The presence of PBDEs in Antarctic coastal organisms may originate from atmospheric transport and partly from a contamination by local sources. Although POP levels in Antarctic marine organisms were substantially lower than in Arctic and temperate organisms, very little is known about their toxic effects on these cold-adapted species, with high degree of endemism. PMID- 24237995 TI - History of human activity in coastal southern Brazil from sediment. AB - This study reports results of analysis of sediment cores collected from the Patos Lagoon estuary. This estuary receives materials from land runoff into Patos and Mirim lagoons and from exchange with the adjacent South Atlantic Ocean through a narrow inlet. Sediment from these sources is mostly natural, but additional contributions associated with source/activities related to the port of Rio Grande. The aim of this study was to estimate rates of accumulation of the sediments and to assess the significance of metal inputs from these activities relative to natural inputs. Our results indicate an average sedimentation rate of 0.3 cm/yr and that the transport of suspended solids from offshore sources into the estuary was enhanced after the deepening of the channel and construction of the breakwaters (in the early 1900). Results for metal accumulation in these sediments suggest that there have been only minor enrichments which can be attributed to anthropogenic sources. PMID- 24237996 TI - Three dimensional marine seismic survey has no measurable effect on species richness or abundance of a coral reef associated fish community. AB - Underwater visual census was used to determine the effect of a three dimensional seismic survey on the shallow water coral reef slope associated fish community at Scott Reef. A census of the fish community was conducted on six locations at Scott Reef both before and after the survey. The census included small site attached demersal species belonging to the family Pomacentridae and larger roving demersal species belonging to the non-Pomacentridae families. These data were combined with a decade of historical data to assess the impact of the seismic survey. Taking into account spatial, temporal, spatio-temporal and observer variability, modelling showed no significant effect of the seismic survey on the overall abundance or species richness of Pomacentridae or non-Pomacentridae. The six most abundant species were also analysed individually. In all cases no detectable effect of the seismic survey was found on the abundance of these fish species at Scott Reef. PMID- 24237997 TI - Development, coinfection, and the syndemics of pregnancy in Sub-Saharan Africa. AB - Notable among gaps in the achievement of the global health Millennium Development Goals (MDG) are shortcomings in addressing maternal health, an issue addressed in the fifth MDG. This shortfall is particularly acute in Sub-Saharan Africa (SSA), where over half of all maternal deaths occur each year. While there is not as yet a comprehensive understanding of the biological and social causes of maternal death in SSA, it is evident that poverty, gendered economic marginalization, social disruptions, hindered access to care, unevenness in the quality of care, illegal and clandestine abortions, and infections are all critical factors. Beyond these factors, this paper presents a review of the existing literature on maternal health in SSA to argue that syndemics constitute a significant additional source of maternal morbidity and mortality in the region. Increasing focus on the nature, prevention, and treatment of syndemics, as a result, should be part and parcel of improving maternal health in SSA. PMID- 24238002 TI - Quantifying soft tissue loss in facial aging: a study in women using magnetic resonance imaging. AB - BACKGROUND: Facial aging involves changes in the facial skeleton and soft tissues. There is limited quantitative data on soft tissue aging of the face. OBJECTIVE: Magnetic resonance imaging (MRI) was used to quantify and compare facial soft tissue loss over time. METHODS AND MATERIALS: Two thousand thirty seven MRI scans from 58 women divided into young, middle-aged, and older groups were screened. A blinded radiologist used MRI to measure the temporal, infraorbital, and medial and lateral cheek areas. RESULTS: The mean thickness of the subcutaneous tissue in the temporal area was 12.3, 8.4, and 8.9 mm in the young, middle-aged, and older groups, respectively (p < .001). A mean difference of 1.6 mm was seen between the young and middle-aged groups and 2.2 mm between the young and older group (p < .001) in the infraorbital area, 3.3 mm between the young and middle-aged groups and 3.2 mm between the young and older group in the medial cheeks (p < .001), and 2.4 mm between the young and middle-aged groups and 2.4 mm between the young and older group in the lateral cheeks (p = .01). CONCLUSIONS: Facial soft tissue undergoes significant deterioration over time, with the most dramatic changes between the ages of 30 and 60 in the temporal, infraorbital, and lateral and medial cheek areas. Soft tissue augmentation and volume correction in these areas may be an effective strategy for facial rejuvenation. PMID- 24238004 TI - Perspectives on integrated behavioral health care. PMID- 24238003 TI - Critical care nurses' experiences of helicopter transfers. AB - BACKGROUND: Intensive care is conducted in intensive care units (ICUs), and also during the transportation of critically ill people. AIM: The aim of the study was to describe critical care nurses' (CCNs) experiences of nursing critically ill patients during helicopter transport. PARTICIPANTS: Seven CCNs, five women and two men participated in this study. DESIGN: Seven participants from two centres in Sweden were recruited. The design uses an inductive, qualitative approach with data collected by means of qualitative interviews with seven CCNs. METHODS: The interviews were transcribed verbatim and subjected to qualitative thematic content analysis. RESULTS: The analysis resulted in one theme which is safe nursing care, but sometimes feeling afraid and six categories as follows: experiencing the care environment as an ICU with limited space; a loud environment complicates communication; planning and checking to minimize risks; experience and good co-operation; facing the dilemma of allowing relatives to accompany the patient or not; feeling the patient's and their own fear. CONCLUSION: CCNs plan for the transportation and control of patients to improve patient safety, but can sometimes feel afraid. Good co-operation is necessary. RELEVANCE TO CLINICAL PRACTICE: The possibilities for CCNs to provide effective nursing care in helicopters are good, although in some cases limited by the environmental conditions. PMID- 24237998 TI - Delirium in acute promyelocytic leukemia patients: two case reports. AB - BACKGROUND: Delirium is a frequently misdiagnosed and inadequately treated neuropsychiatric complication most commonly observed in terminally ill cancer patients. To our knowledge this is the first report describing delirium in two patients aged less than 60 years and enrolled in an intensive chemotherapeutic protocol for acute promyelocytic leukemia. CASE PRESENTATION: Two female Caucasian acute promyelocytic leukemia patients aged 46 and 56 years developed delirium during their induction treatment with all-trans retinoic acid and idarubicin. In both cases symptoms were initially attributed to all-trans retinoic acid that was therefore immediately suspended. In these two patients several situations may have contribute to the delirium: in patient 1 a previous psychiatric disorder, concomitant treatments with steroids and benzodiazepines, a severe infection and central nervous system bleeding while in patient 2 steroid treatment and isolation. In patient 1 delirium was treated with short-term low doses of haloperidol while in patient 2 non-pharmacologic interventions had a beneficial role. When the diagnosis of delirium was clear, induction treatment was resumed and both patients completed their therapeutic program without any relapse of the psychiatric symptoms. Both patients are alive and in complete remission as far as their leukemia is concerned. CONCLUSIONS: We suggest that patients with acute promyelocytic leukemia eligible to intensive chemotherapy should be carefully evaluated by a multisciplinary team including psychiatrists in order to early recognize symptoms of delirium and avoid inadequate treatments. In case of delirium, both pharmacologic and non-pharmacologic interventions may be considered. PMID- 24238000 TI - Lack of access to health care for African indigents: a social exclusion perspective. AB - BACKGROUND: Lack of access to health care is a persistent condition for most African indigents, to which the common technical approach of targeting initiatives is an insufficient antidote. To overcome the standstill, an integrated technical and political approach is needed. Such policy shift is dependent on political support, and on alignment of international and national actors. We explore if the analytical framework of social exclusion can contribute to the latter. METHODS: We produce a critical and evaluative account of the literature on three themes: social exclusion, development policy, and indigence in Africa-and their interface. First, we trace the concept of social exclusion as it evolved over time and space in policy circles. We then discuss the relevance of a social exclusion perspective in developing countries. Finally, we apply this perspective to Africa, its indigents, and their lack of access to health care. RESULTS: The concept of social exclusion as an underlying process of structural inequalities has needed two decades to find acceptance in international policy circles. Initial scepticism about the relevance of the concept in developing countries is now giving way to recognition of its universality. For a variety of reasons however, the uptake of a social exclusion perspective in Africa has been limited. Nevertheless, social exclusion as a driver of poverty and inequity in Africa is evident, and manifestly so in the case of the African indigents. CONCLUSION: The concept of social exclusion provides a useful framework for improved understanding of origins and persistence of the access problem that African indigents face, and for generating political space for an integrated approach. PMID- 24238001 TI - The work environment of haemodialysis nurses and its impact on patients' outcomes. AB - The aims of this study were to assess haemodialysis nurses' work environment and investigate the correlation between work environment and patients' outcomes. A cross-sectional study was conducted at the 11 public hospital-based haemodialysis units of the 5th Regional Health Authority of Greece. The Practice Environment Scale of the Nursing Work Index (PES-NWI) was used to assess work environment. Nurses were asked to report the frequency of a series adverse events and errors. Study population consisted of 133 nurses (response rate 89.3%). The overall PES NWI scored just < 2.5 (Mean = 2.48, standard deviation = 0.34) indicating a non favourable haemodialysis workplace. Nurse-physician Relations, nurse manager ability and nursing foundations for quality of care were the most favourable aspects of work environment. Multivariate logistic regression analysis identified that hypotension (odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.1-0.9, P = 0.03), venous needle disconnection (OR = 0.14, 95% CI = 0.03-0.65, P = 0.012) and patient fall (OR = 0.02, 95% CI = 0.001-0.51, P = 0.018) were associated with a non-favourable work environment. Findings have important implications for improvement of haemodialysis work environment and enhancement of patients' safety. PMID- 24238006 TI - Feasibility evaluation of an interpersonal and social rhythm therapy group delivery model. AB - The effectiveness of psychotherapies, such as interpersonal and social rhythm therapy (IPSRT), is supported by randomized controlled trials. These trials provide minimal direction regarding feasibility of psychotherapy delivery models. The study purpose was to identify factors facilitating implementation and sustainability of an IPRST group for patients with bipolar disorder. Qualitative data were assessed by the normalization process model (NPM). The results demonstrate feasibility of implementation with experienced clinicians, program coordination, and leadership support. Sustainability challenges include aftercare groups, space, and clinician time. The NPM provides a useful framework for evaluation of factors influencing the feasibility of psychotherapy delivery models. PMID- 24238005 TI - Concept analysis: resilience. AB - This paper will systematically analyze the concept of resilience using an integrated review of literature. The historical perspective, attributes, antecedents, and consequences of resilience will be reviewed. A theoretical and operational definition will be provided. The Walker and Avant method will be used to describe the cases. Finally, the use of concept map will capture the relationships among the attributes, antecedents, consequences, and empirical indicators through clustering and chaining. PMID- 24238010 TI - Psychosocial outcomes in young adults with cancer: emotional distress, quality of life and personal growth. AB - This study aimed at assessing the psychosocial adjustment, specifically the emotional distress, quality of life (QOL) and personal growth, in a sample of 36 Portuguese young adults with cancer and 435 healthy controls. Cancer patients scored significantly lower than controls in the role, cognitive and social domains of QOL and in personal growth. Cancer patients scored significantly lower than off-treatment survivors in the role domain of QOL and personal growth. Cancer patients revealed QOL and personal growth difficulties. These issues need to be considered in the psychosocial intervention within adolescents and young adults' oncology care. PMID- 24237999 TI - Remission in rheumatoid arthritis patients treated with etanercept monotherapy: clinical practice and clinical trial experience. AB - OBJECTIVES: To assess, in a randomised controlled trial (RCT) and in clinical practice, an association of time to remission and baseline disease activity with both induction of remission and sustained remission in etanercept-treated patients with rheumatoid arthritis (RA). METHODS: Data from an RCT (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes [TEMPO]; n=682) and an observational registry (Rheumatoid Arthritis DMARD Intervention and Utilization Study [RADIUS II]; n=4341) were used to evaluate disease activity (Clinical Disease Activity Index [CDAI] score) over time in patients initiating etanercept (monotherapy or with methotrexate). CDAI remission (CDAI<=2.8) and sustained remission (>=6 months) were determined through year 3 by treatment group, study, time to remission, and disease severity. RESULTS: Patients from TEMPO and RADIUS II who received etanercept monotherapy showed similar CDAI remission rates (39% and 35%, respectively, at 3 years). Among patients who received etanercept with methotrexate, remission rates were 54% and 36%, respectively. Remission occurred more rapidly in TEMPO than RADIUS II perhaps from differences in compliance, patient populations, or sequence of combination therapy initiation. Generally, more patients with lower baseline CDAI scores achieved remission than those with higher scores. Continued remission appeared more likely in patients achieving remission earlier in the course of their therapy (0-6 months). CONCLUSIONS: Remission by year 3 in etanercept-treated (with and without methotrexate) patients with RA occurred in >=35% of patients in both an RCT (TEMPO) and a clinical practice setting (RADIUS II), and more frequently in those with lower baseline disease severity. Patients with lower RA disease activity were more likely to reach remission. Continued remission may be more likely in patients who achieved remission earlier. PMID- 24238007 TI - Using community-based participatory research to explore social determinants of women's mental health and barriers to help-seeking in three urban, ethnically diverse, impoverished, and underserved communities. AB - Depression and anxiety are significant mental health issues that affect urban, ethnically diverse, impoverished women disproportionately. This study sought to identify social determinants of mental health and barriers to help-seeking for this population. Using community based participatory research and focus groups, sixty-one Black, Hispanic, and White women identified economic, family, cultural, and neighborhood issues as perceived determinants of their depression/anxiety. They identified practical, psychosocial, and cultural barriers to their help seeking behavior. These results can promote women's health by fostering an understanding of social factors as perceived determinants of depression/anxiety and shaping practice and policy initiatives that foster positive aggregate outcomes. PMID- 24238009 TI - Childhood sibling and peer relationships of perpetrators of child sexual abuse. AB - Maltreatment by parents inhibits a child's ability to form relationships with other children. Given that many sex offenders experienced parental abuse, investigation of their relationships with siblings and peers could provide new directions for early childhood interventions. Interview transcripts of 23 community-dwelling perpetrators of sexual abuse against children were examined in this secondary data analysis. Ages of participants ranged from 20s to 70s, and education ranged from GED to PhD. Phenomenological analysis revealed that neither sibling nor peer relationships adequately promoted participants' capacity for developing and maintaining healthy relationships in adulthood. Until societal preventive actions and early clinical interventions are more successful, the crime of child sexual abuse will continue to be far too common. PMID- 24238011 TI - Daily life dialogue assessment in psychiatric care-face validity and inter-rater reliability of a tool based on the International Classification of Functioning, Disability and Health. AB - This article describes the development of an assessment tool based on the International Classification of Functioning Disability and Health (ICF) adapted to a psychiatric nursing context where both the patient and the nurse assess the patient's ability to participate in various spheres of life. The aim was to test psychometric properties, focusing on face validity and inter-rater reliability. Three Swedish expert groups participated. Analysis of inter-rater reliability was conducted through simulated patient cases. The results of an unweighted kappa value of 0.38, a linear weighted kappa value of 0.65 and a quadratic weighted kappa value of 0.73 were considered as acceptable when using simulated patient cases. PMID- 24238012 TI - The phenomena of auditory hallucination as described by Indonesian people living with schizophrenia. AB - This study was a phenomenological inquiry of the experience of auditory hallucinations as described by 13 Indonesian people diagnosed with schizophrenia. The interviewees included 6 men and 7 women and they were aged between 19 and 56 years. Four themes emerged from this study: feeling more like a robot than a human being; voices of contradiction--a point of confusion; tattered relationships and family disarray; and normalizing the presence of voices as part of everyday life. The findings of this study have the potential to contribute to new understandings of how people live with and manage auditory hallucinations and so enhance client-centered nursing care. PMID- 24238013 TI - Exploration of the burnout syndrome occurrence among mental health nurses in Cyprus. AB - Nurses' work-related stress might be associated with psychiatric symptoms, leading to altered professional attitudes. The aim of this study was to explore the levels of burnout and associations with anxiety and depressive symptoms among Greek-Cypriot psychiatric-mental health nurses (PMHNs). A descriptive correlational design with cross-sectional comparisons was applied. A sample of 226 PMHNs was used. Participants reported low levels of burnout. However, 10% of them manifested clinically significant anxiety and depressive symptoms. Emotional exhaustion and depersonalization were associated with depressive (r=0.562, p<0.0001, and r=0.616, p<0.0001, respectively) and anxiety (r=0.394, p<0.0001, and r=0.448, p<0.0001, respectively) symptoms. Further research investigating the biological aetiopathology of these psychological alterations is warranted. PMID- 24238008 TI - Pioneering the psychiatric nurse role in foster care. AB - Older youth served in the foster care system have elevated rates of mental health disorders and are high users of mental health services, yet concerns have been raised about the quality of this care. This paper describes the details of a psychiatric nurse's work within a multidisciplinary team to address gaps in care for older youth with psychiatric disorders. We describe the process, outcomes, and lessons learned in developing and piloting a psychiatric nurse intervention for older youth in the foster care system as part of a multidimensional treatment foster care program. Our experiences support further work to develop a role for nursing to improve the quality of mental health treatment in foster care. PMID- 24238014 TI - Quality of work life as a predictor of nurses' intention to leave units, organisations and the profession. AB - AIM: To examine the relationships between quality of work life (QWL) and nurses' intention to leave their unit (ITLunit), organisation (ITLorg) and profession (ITLpro). BACKGROUND: The high turnover rate among nurses presents a major challenge to health care systems across the globe. QWL plays a significant role in nurses' turnover. METHODS: A descriptive cross-sectional survey design was conducted via purposive sampling of 1283 hospital nurses and administering the Chinese version of the Quality of Nursing Work Life scale (C-QNWL), a three-ITL type scale questionnaire, and a demographic questionnaire for individual- and work-related variables. Descriptive data, correlations, and ordinal regression models were analyzed. RESULTS: QWL predicted ITLpro and ITLorg better than ITLunit. Three QWL dimensions (work arrangement and workload, nursing staffing and patient care, and work-home life balance) were significantly predictive of all three ITL measures. However, the dimension of teamwork and communication was only predictive for ITLunit, not for ITLorg and ITLpro. CONCLUSIONS: Different patterns of QWL dimensions are predictive of ITLunit, ITLorg, and ITLpro. IMPLICATIONS FOR NURSING MANAGEMENT: The study provides important information to nurse administrators about the aspects of QWL that most commonly lead nurses to leave their units, organisations, and even the profession itself. PMID- 24238016 TI - Related flavonoids cause cooperative inhibition of the sarcoplasmic reticulum Ca2+ ATPase by multimode mechanisms. AB - Flavonoids are group of plant-derived hydroxylated polycyclic molecules found in fruit and vegetables. They are known to bio-accumulate within humans and are considered to have beneficial health effects, including cancer chemoprotection. One mechanism proposed to explain this is that they are able to induce apoptosis in cancer cells by inhibiting a variety of kinases and also the Ca2+ ATPase. An investigation was undertaken with respect to the mechanism of inhibition for three flavonoids: quercetin, galangin and 3,6 dihydroxyflavone (3,6-DHF). Each inhibited the Ca2+ ATPase with K(i) values of 8.7, 10.3 and 5.4 MUM, respectively, showing cooperative inhibition with n ~ 2. Given their similar structures, the flavonoids showed several differences in their mechanisms of inhibition. All three flavonoids stabilized the ATPase in the E1 conformation and reduced [32P]-ATP binding. However, both galangin and 3,6-DHF increased the affinity of Ca2+ for the ATPase by decreasing the Ca2+-dissociation rate constant, whereas quercetin had little effect. Ca2+-induced changes in tryptophan fluorescence levels were reduced in the presence of 3,6-DHF and galangin (but not with quercetin), indicating that Ca2+-associated changes within the transmembrane helices are altered. Both galangin and quercetin reduced the rates of ATP dependent phosphorylation and dephosphorylation, whereas 3,6-DHF did not. Modelling studies suggest that flavonoids could potentially bind to two sites: one directly where nucleotides bind within ATP binding site and the other at a site close by. We hypothesize that interactions of these two neighbouring sites may account for both the cooperative inhibition and the multimode mechanisms of action seen with related flavonoids. PMID- 24238019 TI - [Focus on health care resources]. PMID- 24238022 TI - [Health insurance expenses for children in the first five years of life - a cohort-based analysis]. AB - INTRODUCTION: The development of paediatrics is characterised by several changes in the past few years, concerning, in particular holistic treatments or preventive check-ups, but also the transfer of treatment from the inpatient to the outpatient sector. There are no reference values for assessing emerging health insurance expenses. The aim of this study was to obtain a frame of reference for the costs of the treatment for neonates, infants, and young children using the example of the expenditures of one health insurance fund. METHODS: The individual health insurance expenditures were analysed for the first five years of life of children insured with the AOK PLUS in Saxony, Germany, in 2005. Costs of hospital treatment, ambulatory care, remedies, tools, medicines and care were included. RESULTS: The costs per insured child and year amounted to approximately 1,277 Euro (N = 11,147), with the highest costs arising in the first two years. 858 Euro were spent annually for an "average" child; 5,691 Euro per year incurred for a child with special medical needs. DISCUSSION: The present cost analysis describes both the height and structure of a health insurance's spendings on children within the first five years of their life in consideration of regional medical care offers. The question of whether this analysis provides valid reference values for other health insurances or other service areas will have to be answered by other analyses. PMID- 24238023 TI - [The costs of new drugs compared to current standard treatment]. AB - BACKGROUND: Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. METHOD: We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. RESULTS: If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. PMID- 24238015 TI - Facilitative plant interactions and climate simultaneously drive alpine plant diversity. AB - Interactions among species determine local-scale diversity, but local interactions are thought to have minor effects at larger scales. However, quantitative comparisons of the importance of biotic interactions relative to other drivers are rarely made at larger scales. Using a data set spanning 78 sites and five continents, we assessed the relative importance of biotic interactions and climate in determining plant diversity in alpine ecosystems dominated by nurse-plant cushion species. Climate variables related with water balance showed the highest correlation with richness at the global scale. Strikingly, although the effect of cushion species on diversity was lower than that of climate, its contribution was still substantial. In particular, cushion species enhanced species richness more in systems with inherently impoverished local diversity. Nurse species appear to act as a 'safety net' sustaining diversity under harsh conditions, demonstrating that climate and species interactions should be integrated when predicting future biodiversity effects of climate change. PMID- 24238021 TI - [Which chronic diseases are associated with frequent attending of ambulatory medical care in the elderly population in Germany? - A study based on statutory health insurance data]. AB - BACKGROUND: Frequent attenders utilise a high proportion of medical services and therefore produce relatively high costs. Questions of utility and adequacy and, also, about the reasons for high use arise. The authors report the results of a study on the association between morbidity of the elderly and various forms of frequent attendance in ambulatory medical care in Germany. METHODS: The study is based on claims data of all policyholders aged 65 and over of a statutory health insurance company operating nationwide in Germany in 2004 (n = 123,224). Utilisation was analysed by the number of contacts with practices of physicians working in the ambulatory medical care sector and by the number of different practices contacted. Criteria for frequent attendance were >= 50 contacts with practices or contacts with >= 10 individual practices or >= 3 practices of the same discipline per year. We analysed prevalences and relative risks for frequent attendance for 46 chronic diseases. RESULTS: Frequent attendance in ambulatory medical care among the elderly is related to both severe somatic and psychic diagnoses. Five chronic diseases showed the highest relative risks for all types of frequent attendance in general: urinary incontinence, anaemia, neuropathies, renal insufficiency, and cancer. Psychic syndromes mainly led to the utilisation of many different physicians. CONCLUSION: Frequent attendance in ambulatory medical care among the elderly is related to a large number of diseases, both somatic and psychic. Frequent attendance is a complex phenomenon which cannot be addressed by mono-dimensional approaches. PMID- 24238018 TI - A novel biomarker-based approach for the detection of asymptomatic brain injury during catheter ablation of atrial fibrillation. AB - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is a widely used method for studying of asymptomatic brain injury during catheter ablation of atrial fibrillation (AF). However, this technique lacks sensitivity for subtle or diffuse brain lesions. We investigated whether detection of the ablation-related brain injury can improve by assessment of a biomarker of brain damage-protein S100B. METHODS AND RESULTS: DW-MRI and assessment of S100B were performed in 58 patients undergoing radiofrequency catheter ablation of paroxysmal or persistent AF 1 day before and after the procedure. We observed no symptomatic neurological complications. S100B levels increased after ablation above the upper reference limit of 105 ng/L in 3 patients. One of them developed a new ischemic lesion on the DW-MRI. No acute lesions emerged on DW-MRI in the patients with normal postablation S100B levels. CONCLUSION: Serial assessment of serum protein S100B may improve detection of asymptomatic acute brain injury in patients undergoing radiofrequency catheter ablation of AF. In our study, the incidence of these events was 1.7% when evaluated only by DW-MRI, but the incidence increased to 5% after employing the more sensitive biomarker-based approach. PMID- 24238020 TI - [Size and type of frequent use of ambulatory medical care among the elderly population in Germany: a study based on statutory health insurance data]. AB - BACKGROUND: The authors report the results of a study on frequent attenders in ambulatory medical care among elderly people in Germany and on the factors related to frequent attendance such as age, sex, multi-morbidity and long-term care dependency. METHODS: The study was based on claims data of all policy holders aged 65 and over of a statutory health insurance company operating nationwide in Germany in 2004 (n=123,224). Utilisation was analysed by the number of contacts with practices of physicians working in the ambulatory medical care sector and by the number of different practices contacted. The criteria for frequent attendance included greater than or equal to 50 contacts and/or greater than or equal to 10 different practices contacted and/or greater than or equal to 3 practices of the same discipline contacted within one year. Descriptive statistical analysis and logistic regression were used. RESULTS: 19% of the elderly were identified as frequent attenders, which corresponds to some 3.5 million people in Germany. Two main types of frequent attendance were identified: one is characterised by very many contacts, old age, frequent presence of multi morbidity, and/or long-term care dependency. The other type is the younger, less frequently multi-morbid attender who is considerably less often dependent on long term care, and characterised by large numbers of contacted practices and/or practices of the same discipline. CONCLUSION: Frequent attendance is due to several factors. The problem of frequent attendance needs further research that is not exclusively based on claims data. We found a high rate of frequent attendance. Further research should clarify if this is to the benefit of elderly people. PMID- 24238026 TI - [Practice report: Structured training to improve quality of care in emergency medical service. On-scene supervision: A new approach to emergency medical service training in Wiesbaden and Rheingau-Taunus-Kreis?]. AB - In recent years, the emergency medical services in Wiesbaden and the Rheingau Taunus district made great efforts to standardise structures. Since there are only few established procedures in the annual examinations for paramedics, there is reason to assume that treatment procedures for patients have not been standardised either. Materials and equipment are not handled uniformly, and employee satisfaction has significantly decreased over the last few years. To solve these problems, all paramedics undergo standardised and structured trainings. These training courses make use of the internationally accepted PHTLS (Pre-Hospital Trauma Life Support) and AMLS (Advanced Life Support Medial) programmes. In addition, practising skills and handling the equipment as well as on-scene supervision is to be established in practical training sessions. PMID- 24238031 TI - Biometry, keratometry, and calculation of intraocular lens power for the bald eagle (Haliaeetus leucocephalus). AB - OBJECTIVE: To document intraocular measurements and predict intraocular lens (IOL) power specific to the bald eagle. ANIMALS STUDIED: Eleven adult, captive bald eagles. PROCEDURES: Axial globe length (AGL), anterior chamber depth (ACD), crystalline lens thickness (CLT), and the distance from the cornea to the posterior lens capsule (CPLC) were measured in eight adult bald eagles using B mode with vector A-mode ultrasound. Keratometry was done on four eagles. Two estimates for postoperative anterior chamber depth (PACD) were obtained from four aphakic eyes from three eagles by measuring from the apex of the anterior cornea to the center of an imaginary line that would connect the remaining edges of the anterior lens capsule across the capsulorhexis (PACD1) and from the apex of the anterior cornea to halfway between the anterior and posterior lens capsule (PACD2). IOL strength was predicted using the Colenbrander, Binkhorst, and Fyodorov theoretical formulas. RESULTS: Mean +/- SD biometry for phakic eyes was AGL = 26.57 +/- 0.45 mm, ACD = 4.45 +/- 0.18 mm, CLT = 5.49 +/- 0.14 mm, and CPLC = 10.00 +/- 0.33 mm. Mean predicted PACD1 was 6.1 +/- 0.66 mm, and PACD2 was 6.4 +/- 0.70 mm. Mean horizontal and vertical corneal refractive power was 39.91 +/- 0.43 diopters (D) and 40.02 +/- 0.08 D, respectively. Calculated IOL power ranged from +16.4 to 17.4 D. CONCLUSIONS: Calculations using ultrasonographic biometry, keratometry, and theoretical IOL formulas suggest that the strength of an IOL necessary to return an aphakic bald eagle to emmetropia is between +16.4 and +17.4 D. PMID- 24238024 TI - [Medical journals as implicit role models for good multiple choice questions: to which degree have CME tests so far fulfilled formal quality criteria?]. AB - BACKGROUND: Many clinicians, particularly those from university hospitals and associated teaching hospitals, use multiple-choice questions in different professional roles: as examiners for student assessment and as life-long learners in respect to the CME programmes of medical journals. For this group of physicians it might thus be desirable that medical journals serve as implicit role models for formulating high-quality multiple-choice questions. METHOD: 370 multiple-choice questions taken from the 2011 volumes of three different medical journals were reviewed. A checklist consisting of 11 formal quality criteria, 5 quality categories and one global criterion, taken from the literature and from the German Item Management System, was used. RESULTS: High-quality questions were found in the categories "language", "structure", and "signposting the question type." However, "application to cases or problems" and "analysis, interpretation, problem solving" were realised in less than 20 %, and "cues" were detected in almost half of the questions. A subgroup analysis showed different quality levels between the journals. CONCLUSIONS: To serve as role models for high-quality multiple-choice questions (MCQ) German medical journals should deliver formal quality criteria and good writing examples to their MCQ authors and ensure strict adherence to these criteria. The development of journal-independent formal standards might prove worthwhile. PMID- 24238027 TI - [Management of chronic heart failure - a systematic review of guidelines in the context of the DMP revision]. AB - BACKGROUND: Disease Management Programmes (DMPs) are structured treatment programmes for chronic diseases. The DMP requirements are primarily derived from evidence-based guidelines. DMPs are regularly revised to ensure that they reflect current best practice and medical knowledge. The aim of this study was to assess the need for updating the German DMP module on heart failure by comparing it to relevant guidelines and identifying recommendations that should be revised. METHODS: We systematically searched for clinical guidelines on heart failure published in German, English or French, and extracted relevant guideline recommendations. All included guidelines were assessed for methodological quality. To identify revision needs in the DMP, we performed a synoptic analysis of the extracted guideline recommendations and DMP requirements. RESULTS: 27 guidelines were included. The extracted recommendations covered all aspects of the management of heart failure. The comparison of guideline recommendations with DMP requirements showed that, overall, guideline recommendations were more detailed than DMP requirements, and that the guidelines covered topics not included in the DMP module. CONCLUSIONS: The DMP module is largely consistent with current guidelines on heart failure. We did not identify any need for significant revision of the DMP requirements. However, some specific recommendations of the DMP module could benefit from revision. PMID- 24238017 TI - Isolation with differentiation followed by expansion with admixture in the tunicate Pyura chilensis. AB - BACKGROUND: Pyura chilensis, a tunicate commercially exploited as food resource in Chile, is subject to management strategies, including restocking. The goal of this study was to examine the genetic structure of P. chilensis using information from a mitochondrial gene (Cytochrome Oxidase I, COI) and a nuclear gene (Elongation 1 alpha, EF1a), to characterize the geographic distribution of genetic diversity and differentiation, and to identify the main processes that have shaped it. We analyzed 268 and 208 sequences of COI and EF1a, respectively, from samples of eight local populations covering ca. 1800 km. RESULTS: For Pyura chilensis, partial sequences of the gene COI revealed three highly supported haplogroups that diverged 260000 to 470000 years ago. Two haplogroups currently are widely distributed and sympatric, while one is dominant only in Los Molinos (LM, 39 degrees 50'S). The two widespread COI haplogroups underwent a geographic expansion during an interglacial period of the Late Pleistocene ca. 100000 years ago. The nuclear gene was less divergent and did not resolve the COI haplogroups. Bayesian clustering of the nuclear gene's SNPs revealed that individuals from the two widespread COI haplogroups were mostly assigned to two of the three detected clusters and had a marked degree of admixture. The third cluster predominated in LM and showed low admixture. Haplotypic diversity of both genes was very high, there was no isolation by distance, and most localities were genetically undifferentiated; only LM was consistently differentiated with both genes analyzed. CONCLUSIONS: Pyura chilensis has less genetic structure than expected given its life history, which could be a consequence of dispersal on ship hulls. The only differentiated local population analyzed was LM. Coincidentally, it is the one furthest away from main maritime routes along the coast of Chile.The use of mitochondrial and nuclear markers allowed detection of divergent mitochondrial haplogroups in P. chilensis, two of which revealed nuclear admixture. The genetic structure of P. chilensis has likely been shaped by Pleistocene's climatic effect on sea level leading to population contraction with isolation, followed by geographic range expansions with concomitant secondary contact and admixture. PMID- 24238034 TI - Testing the psychometric properties of the Brisbane Practice Environment Measure using Exploratory Factor Analysis and Confirmatory Factor Analysis in an Australian registered nurse population. AB - A cross-sectional survey was conducted, and the construct validity and reliability of the Brisbane Practice Environment Measure in an Australian sample of registered nurses were examined. Nurses were randomly selected from the database of an Australian nursing organization. The original 33 items of the Brisbane Practice Environment Measure were utilized to inform the psychometric properties using confirmatory factor analysis. The Cronbach's alpha was 0.938 for the total scale and ranged 0.657-0.887 for the subscales. A five-factor structure of the measure was confirmed, chi(2) = 944.622, (P < 0.01), chi(2) /d.f. ratio = 2.845, Tucker Lewis Index 0.929, Root Mean Square Error = 0.061 and Comparative Fit Index = 0.906. The selected 28 items of the measure proved reliable and valid in measuring effects of the practice environment upon Australian nurses. The implications are that regular measurement of the practice environment using these 28 items might assist in the development of strategies which might improve job satisfaction and retention of registered nurses in Australia. PMID- 24238025 TI - [Professionalism in general practice in Germany - a qualitative approximation]. AB - BACKGROUND: Pre- and postgraduate education is meant to be competency-based. Over the last two decades various competency frameworks have been published. One competency is professionalism, a definition of which has not yet been developed but is being discussed in the literature. The aim of this qualitative study is an approximation to professionalism among German general practitioners and general practitioner trainees. METHODS: A qualitative study was conducted by interviewing seven pairs of GPs and their trainees. All interviews were recorded and transcribed. The analysis was performed according to Mayring supported by the software Atlas.ti. RESULTS: Four categories of professionalism emerged: responsibility towards patients, responsibility towards other professionals, responsibility towards the society and responsibility towards oneself. Professionalism was perceived as important for general practice in Germany. In addition, barriers of professional behaviour have been identified. CONCLUSION: The perception of professionalism among German GPs and GP trainees is in accordance with the frameworks of professionalism found in the literature. These results underline the need for conceptualising professionalism among general practice trainees in Germany. PMID- 24238032 TI - Effects of promethazine or dexamethasone pretreatment on mivacurium-induced histamine release in children. AB - OBJECTIVE: To determine the effects of pretreatment with either promethazine or dexamethasone on mivacurium-induced histamine release in children. METHODS: Eighty ASA I-II children (4-10 years of age) scheduled for tonsillectomy and/or adenoidectomy were randomly divided into 4 groups (n = 20 per group) designated as either the rocuronium, mivacurium, dexamethasone (DXM), or promethazine group. Children in the DXM and promethazine groups were treated separately with intramuscular DXM 0.2 mg.kg(-1) or promethazine 0.5 mg.kg(-1) injections 60 min before operation. Radial artery blood samples were collected to quantify plasma histamine concentrations 1 min before and 1, 3, and 5 min after administration of the relaxant. Mean arterial pressure (MAP), heart rate (HR), and skin flushing were recorded at the same time. RESULTS: No significant decreases in plasma histamine concentrations were observed between groups; however, more stable MAP and HR and less skin flushing were observed in DXM group participants compared with individuals in the mivacurium group (P < 0.05). By contrast, children in the promethazine group had significantly decreased plasma histamine concentrations and stable MAP and HR (without a significant increase in HR) compared with patients in mivacurium group. In addition, skin flushing was significantly decreased compared with that observed in the rocuronium group (P < 0.05). CONCLUSIONS: Pretreatment with promethazine significantly decreased mivacurium induced histamine release in children and provided stable hemodynamics during administration of anesthesia. PMID- 24238033 TI - An etiological reappraisal of pancytopenia - largest series reported to date from a single tertiary care teaching hospital. AB - BACKGROUND: Peripheral pancytopenia is not a disease by itself; rather it describes simultaneous presence of anemia, leucopenia and thrombocytopenia resulting from a number of disease processes. Only a few systematic studies have been published on the topic of pancytopenia, although extensive studies have been done for its different etiological factors like aplastic anemia, megaloblastic anemia, leukemia, etc. Thus, this study was carried out to investigate for and to identify the causes of pancytopenia, to find out the frequency of different causes, to determine the incidence of pancytopenia in relation to sex and age and to compare our findings with those of other similar studies from this part of the world. METHODS: This was a prospective study conducted in the Department of Pathology of a teaching institute and a tertiary care hospital in southern Maharashtra, India, over a period of two years. All the patients referred to the central clinical laboratory for routine complete blood count (CBC) and peripheral smear (PS) examination, from both - the outpatient and the inpatient departments, were screened for pancytopenia. Of these, a total number of 250 cases that fulfilled the diagnostic criteria were selected.Detailed hematological investigations followed by bone marrow aspiration wherever indicated and possible were performed according to standard methods to ascertain the causes of pancytopenia. RESULTS: A definite male preponderance was observed, the male to female ratio being 2.6 : 1. The majority of cases were encountered in 3rd and 4th decades. Hypersplenism (29.2%), Infections (25.6%), Myelosuppressants (16.8%) and Megaloblastosis (13.2%) were the four most common causes in this large series on pancytopenia from a single centre in India. CONCLUSION: Detailed clinical history and meticulous physical examination along with baseline hematological investigations, provides invaluable information in the complete workup of pancytopenic patients, helping in systematic planning of further investigations to diagnose and ascertain the cause, avoiding a battery of unnecessary tests. PMID- 24238035 TI - MiR-27 orchestrates the transcriptional regulation of brown adipogenesis. AB - OBJECTIVE: Brown adipose tissue (BAT) produces heat using chemical energy of lipids and glucose, a function induced by cold exposure or diet. The brown adipogenesis is tightly controlled in a coordinated interplay between several transcriptional factors. It is not known what enables and coordinates this robust program of concerted cooperation between the transcriptional factors and co regulators necessary for the brown adipogenesis. MATERIALS/METHODS: A. In vivo studies--we investigated the expression levels of miR-27a and b in mice after cold exposure. B. Using gene expression and functional studies together with high throughput imaging in primary preadipocytes, and cell culture models, we investigated the role of miR-27 in beige and brown adipogenesis. C. Using gene silencing and rescue experiments we dissected the molecular mechanisms of the miR 27 action. RESULTS: After cold exposure, miR-27 is downregulated in BAT and subcutaneous white adipose tissue (SAT). MiR-27 is also downregulated during brown adipogenesis of primary preadipocytes in vitro, and it directly targets and negatively regulates the essential components of the brown transcriptional network: Prdm16, Pparalpha, Creb, and in part Pgc1beta. Together with its direct effect on Ppargamma, and indirect on Pgc1alpha, mir-27 decreases brown differentiation of cultured cells and of primary SAT preadipocytes. CONCLUSIONS: Our results point to miR-27 as a central upstream regulator of the transcriptional network involved in beige and brown adipogenesis after cold exposure, and suggest miR-27 inhibition as a novel therapeutic approach for metabolic diseases aiming at increasing the beige/brown fat mass. PMID- 24238037 TI - Natural OX40L expressed on human T cell leukemia virus type-I-immortalized T cell lines interferes with infection of activated peripheral blood mononuclear cells by CCR5-utilizing human immunodeficiency virus. AB - BACKGROUND: OX40 ligand (OX40L) co-stimulates and differentiates T cells via ligation of OX40 that is transiently induced on T cells upon activation, resulting in prolonged T cell survival and enhanced cytokine production by T cells. This view has led to the targeting of OX40 as a strategy to boost antigen specific T cells in the context of vaccination. In addition, the ligation of OX40 has also been shown to inhibit infection by CCR5-utilizing (R5) but not CXCR4 utilizing (X4) human immunodeficiency virus type-1 (HIV-1) via enhancement of production of CCR5-binding beta-chemokines. It was reasoned that human T cell leukemia virus type-I (HTLV-1) immortalized T cell lines that express high levels of OX40L could serve as an unique source of physiologically functional OX40L. The fact that HTLV-1+ T cell lines simultaneously also express high levels of OX40 suggested a potential limitation. RESULTS: Results of our studies showed that HTLV-1+ T cell lines bound exogenous OX40 but not OX40L, indicating that HTLV-1+ T cell lines express an active form of OX40L but an inactive form of OX40. Anti OX40 non-blocking monoclonal antibody (mAb), but not blocking mAb, stained HTLV 1+ T cell lines, suggesting that the OX40 might be saturated with endogenous OX40L. Functionality of the OX40L was confirmed by the fact that a paraformaldehyde (PFA)-fixed HTLV-1+ T cell lines inhibited the infection of autologous activated peripheral blood mononuclear cells (PBMCs) with R5 HIV-1 which was reversed by either anti-OX40L blocking mAb or a mixture of neutralizing mAbs against CCR5-binding beta-chemokines. CONCLUSIONS: Altogether, these results demonstrated that autologous T cell lines immortalized by HTLV-1 can be utilized as a conventional source of physiologically functional OX40L. PMID- 24238038 TI - Effects of Aedes aegypti salivary components on dendritic cell and lymphocyte biology. AB - BACKGROUND: Saliva is a key element of interaction between hematophagous mosquitoes and their vertebrate hosts. In addition to allowing a successful blood meal by neutralizing or delaying hemostatic responses, the salivary cocktail is also able to modulate the effector mechanisms of host immune responses facilitating, in turn, the transmission of several types of microorganisms. Understanding how the mosquito uses its salivary components to circumvent host immunity might help to clarify the mechanisms of transmission of such pathogens and disease establishment. METHODS: Flow cytometry was used to evaluate if increasing concentrations of A. aegypti salivary gland extract (SGE) affects bone marrow-derived DC differentiation and maturation. Lymphocyte proliferation in the presence of SGE was estimated by a colorimetric assay. Western blot and Annexin V staining assays were used to assess apoptosis in these cells. Naive and memory cells from mosquito-bite exposed mice or OVA-immunized mice and their respective controls were analyzed by flow cytometry. RESULTS: Concentration-response curves were employed to evaluate A. aegypti SGE effects on DC and lymphocyte biology. DCs differentiation from bone marrow precursors, their maturation and function were not directly affected by A. aegypti SGE (concentrations ranging from 2.5 to 40 MUg/mL). On the other hand, lymphocytes were very sensitive to the salivary components and died in the presence of A. aegypti SGE, even at concentrations as low as 0.1 MUg/mL. In addition, A. aegypti SGE was shown to induce apoptosis in all lymphocyte populations evaluated (CD4+ and CD8+ T cells, and B cells) through a mechanism involving caspase-3 and caspase-8, but not Bim. By using different approaches to generate memory cells, we were able to verify that these cells are resistant to SGE effects. CONCLUSION: Our results show that lymphocytes, and not DCs, are the primary target of A. aegypti salivary components. In the presence of A. aegypti SGE, naive lymphocyte populations die by apoptosis in a caspase-3- and caspase-8-dependent pathway, while memory cells are selectively more resistant to its effects. The present work contributes to elucidate the activities of A. aegypti salivary molecules on the antigen presenting cell-lymphocyte axis and in the biology of these cells. PMID- 24238039 TI - Presidential address: a new face for endocrine surgery. PMID- 24238036 TI - Ruxolitinib for myelofibrosis--an update of its clinical effects. AB - Myelofibrosis (MF), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by progressive bone marrow fibrosis and ineffective hematopoiesis. Clinical hallmarks include splenomegaly, anemia, and debilitating symptoms. In 2 randomized phase III studies, the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib significantly improved splenomegaly and disease-related symptoms compared with placebo (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment [COMFORT-I]) or best available therapy (COMFORT-II) in patients with intermediate-2 or high-risk MF. Although ruxolitinib therapy was associated with dose-dependent anemia and thrombocytopenia, these adverse events rarely led to treatment discontinuation. This update of the clinical effects of ruxolitinib in patients with MF was based on original articles and meeting abstracts published after the primary publication of the COMFORT trials in March 2012. Long-term follow-up data from the COMFORT trials and clinical experience with ruxolitinib in unselected patient populations suggest that improvement of splenomegaly and symptoms is durable. Patients benefit from ruxolitinib therapy across subgroups defined by age, MF type, risk category, performance status, JAK2 V617F mutation status, extent of splenomegaly, or presence of cytopenias. In COMFORT-I, platelet counts stabilized with dose adjustments, and hemoglobin levels gradually recovered to slightly below baseline after the first 8 to 12 weeks of therapy. After initial increases, the need for red blood cell transfusions decreased to a level similar to that found in the placebo group. The 2-year follow-up data from the COMFORT trials suggest that patients with intermediate-2 or high-risk MF receiving ruxolitinib therapy may have improved survival compared with those receiving no (placebo) or traditional therapy. PMID- 24238040 TI - Is routine prophylactic central neck dissection indicated for low-risk papillary thyroid cancer: can we determine cost-effectiveness if we are unsure about its effectiveness and safety? PMID- 24238041 TI - A new tool: the same dilemma. PMID- 24238042 TI - Observation of clinically negative central compartment lymph nodes in papillary thyroid carcinoma. AB - BACKGROUND: The role of prophylactic central neck dissection in the management of papillary thyroid cancer (PTC) is controversial. We report our experience of an observational approach to the cN0 neck in PTC. METHODS: We reviewed 1,129 patients with PTC who had total thyroidectomy between 1986 and 2005. In that group, 470 patients were pN1; 384 had benign nodes removed (pN0); and the remaining 275 had no nodes removed (pNx). The pNx group formed the cohort for this study. RESULTS: With a median follow-up of 70 months, the 10-yr disease specific survival was 100%. We found 4 patients who had evidence of radioactive iodine uptake on scans performed during follow-up without diagnostic cytology. All subsequently received radioactive iodine and are considered disease free. Three patients had biopsy-proven lateral-neck recurrence and underwent neck dissection; 1 patient developed a low-level thyroglobulin suspicious for recurrence; and 1 patient had a subcentimeter level VI node suspicious for recurrence, which has been observed. Therefore, the rate of structural recurrence in the central neck was 0.4% (1/275), and the rate of reoperation on the central neck was 0. CONCLUSION: Our results suggest that properly selected patients can be managed safely with observation of the central neck rather than prophylactic central neck dissection, which has a higher complication rate. PMID- 24238043 TI - Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors. AB - BACKGROUND: Ligands binding the somatostatin receptor type 2 (SSTR2) are useful for imaging and treatment of neuroendocrine tumors (NETs), but not all tumors express high levels of these receptors. The aim of this study was to evaluate gene expression of new therapeutic targets in NETs relative to SSTR2. METHODS: RNA was extracted from 103 primary small bowel and pancreatic NETs, matched normal tissue, and 123 metastases. Expression of 12 candidate genes was measured by quantitative polymerase chain reaction normalized to internal controls; candidate gene expression was compared with SSTR2. RESULTS: Relative to normal tissue, primary NET expression of SSTR2, GPR98, BRS3, GIPR, GRM1, and OPRK1 were increased by 3, 8, 13, 13, 17, and 20-fold, respectively. Similar changes were found in metastases. Although most candidate genes showed lesser absolute expressions than SSTR2, absolute GIPR expression was closest to SSTR2 (mean dCT 3.6 vs. 2.7, P = .01). Absolute OPRK1 and OXTR expression varied greatly by primary tumor type and was close to SSTR2 in small bowel NETs but not pancreatic NETs. CONCLUSION: Compared with the current treatment standard SSTR2, GIPR has only somewhat lesser absolute gene expression in tumor tissue but much lesser expression in normal tissue, making it a promising new target for NET imaging and therapy. PMID- 24238044 TI - Adrenalectomy for solid tumor metastases: results of a multicenter European study. AB - BACKGROUND: We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers. METHODS: Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible. RESULTS: Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (<=6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86% of cases. The median overall survival was 29 months (95% confidence interval, 24.69 33.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%, 42%, and 35%, respectively. Patients with renal cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P = .017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs. 23 months; P = .038). CONCLUSION: Surgical removal of adrenal metastasis is associated with long-term survival in selected patients. PMID- 24238045 TI - MiR-34a and miR-483-5p are candidate serum biomarkers for adrenocortical tumors. AB - BACKGROUND: Nonfunctioning adrenal incidentalomas are common and many patients undergo adrenalectomy to exclude adrenocortical carcinoma (ACC). Recent studies have shown dysregulated microRNA (miRNA) expression in ACC. The objective of this study was to determine the feasibility and diagnostic accuracy of measuring serum miRNAs in patients with benign and malignant adrenocortical neoplasms. METHOD: Five miRNAs were selected from miRNA profiling studies in ACC (miR-let-7d, -34a, 195, -214, and 483-5p). Total miRNA was extracted from serum samples in patients with malignant and benign adrenal neoplasms. miRNAs levels were measured by quantitative reverse transcript polymerase chain reaction and normalized to miR 16. To determine if miRNAs were secreted from ACC cells, we measured miRNA levels in culture. RESULTS: Serum samples from 22 patients with cortical adenomas and 17 patients with ACC were analyzed, and all 5 miRNAs were detected. We found greater levels of miR-34a (P = .001) and miR-483-5p (P = .011) in patients with ACC. The area under the receiver operating characteristic curve was 0.81 for miR-34a and 0.74 for miR-438-5p. MiR-34a and miR-483-5p levels in ACC cells were greater in the supernatant at 48 hours compared with intracellular levels. CONCLUSION: We show that dysregulated miRNAs in ACC are detectable in human serum samples. MiR 34a and miR-483-5p are candidate serum biomarkers for distinguishing between benign and malignant adrenocortical tumors. PMID- 24238046 TI - Under-recognition of the benefits of parathyroidectomy leads to underdiagnosis of the disease. PMID- 24238047 TI - The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma. AB - BACKGROUND: Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. METHODS: We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. RESULTS: There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P < .001) and had a younger median age (43 vs. 47 years; P = .03), a lesser incidence of CNM (35% vs. 52.4%; P < .001), and a greater incidence of pT1a (40% vs. 25%; P < .001) and pT1b (38% vs. 29%; P < .001) tumors. Multivariate analysis showed that the presence of CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. CONCLUSION: Female patients of all ages with CLT and small PTCs have the least incidence of CNM. PMID- 24238048 TI - Operative intervention for recurrent adrenocortical cancer. AB - INTRODUCTION: Adrenocortical cancer (ACC) recurs despite apparent complete resection. We examined the survival and palliative benefit of resection for recurrent ACC. METHODS: A review of all patients undergoing operation for ACC between 1980 and 2010 at our institution was performed in which we compared resection with nonoperative therapy. RESULTS: Overall, 164 patients underwent operation for ACC, 125 of whom underwent a complete resection (R0). Recurrence occurred in 93 R0 patients (median, 15 months; range, 1.5-150 months). Symptoms at recurrence were present in 71% (66/93), including pain (34%) and hormone excess (43%). There were 67 patients who underwent reoperation for recurrence. Forty-eight of 67 patients underwent R0 resection for recurrence. Operative patients had a greater overall operative versus nonoperative management or no therapy (65 months vs 6 months, P < .01). Median survival for nonoperatively managed patients (226 days) and those undergoing no therapy (179 days) was less than for debulking (1,272 days, P = .002). R0 for recurrence (P = .005) and a disease-free interval >6 months (P < .001) were associated with survival after operation, whereas original tumor size (P = .47), grade (P = .8), and stage (P = .23) were not. Pain and hormonal symptoms improved in 84% of operative patients versus 29% of nonoperatively managed patients (P = .005). Debulking had similar symptomatic improvement to R0 resection (P = .52). CONCLUSION: Patients with recurrent ACC can benefit from operative intervention with improvement in survival and symptoms. Patients with a disease-free interval >6 months and complete resection are likely to benefit from resection of the recurrence, but the near universal improvement in symptoms may expand the criteria for operation in recurrent ACC. PMID- 24238049 TI - Cost analysis of thyroid lobectomy and intraoperative frozen section versus total thyroidectomy in patients with a cytologic diagnosis of "suspicious for papillary thyroid cancer". AB - BACKGROUND: The optimal operation for a patient with a thyroid nodule "suspicious for papillary thyroid cancer (PTC)" on fine-needle aspiration (FNA) is unclear. This study examines the incremental cost-utility of thyroid lobectomy with intraoperative frozen section (thyroid lobectomy) versus total thyroidectomy. METHODS: Cost-utility analysis was performed for patients with a cytologic diagnosis of "suspicious for PTC" on FNA. Patients underwent either initial total thyroidectomy or thyroid lobectomy and, if needed, completion thyroidectomy. The incremental cost-utility ratio (ICUR; US$/quality-adjusted-life-year [QALY]), was determined from a societal perspective. RESULTS: The base-case ICUR of thyroid lobectomy is $90,776/QALY, strongly favoring total thyroidectomy as a more cost effective modality. On sensitivity analyses, the model is sensitive to the accuracy of frozen section and to the rate of injury to the recurrent laryngeal nerve (RLN). Thyroid lobectomy is more cost-effective only if both frozen section and final pathology are benign in >=92% of patients (ICUR $47,959/QALY at 92%). With increasing rates of unilateral (>5%) or bilateral (>2%) RLN injury associated with total thyroidectomy, there is a trend toward thyroid lobectomy being more cost effective ($53,127 and $51,325/QALY, respectively). CONCLUSION: In our model, initial total thyroidectomy is cost-effective for patients with a single thyroid nodule suspicious for PTC on FNA. Our results strongly support total thyroidectomy for initial treatment; thyroid lobectomy is preferred only when complications reach unacceptable levels. PMID- 24238050 TI - Prospective analysis of coronary calcium in patients on dialysis undergoing a near-total parathyroidectomy. AB - BACKGROUND: Patients with secondary hyperparathyroidism and on dialysis are more likely to die of cardiovascular disease than the general population; and we have reported that near-total parathyroidectomy (NTPTX) reduces that mortality rate. Patients on dialysis experience an average of a 15% increase in coronary calcification yearly, contributing to cardiovascular death. Cardiac computed tomography (CT) enables objective measuring of coronary calcium. The purpose of our study was to determine the impact of NTPTX on coronary artery calcium score (CACS). METHODS: CACS measurement was performed in patients with stage 5 chronic kidney disease before and after NTPTX from 2001 to 2008. Demographics, morbidities, CACS, outcomes, intact parathyroid hormone (PTH) measurements in follow-up (mean, 5.1 years) were maintained in an institutional review board approved prospective database. Of 31 patients, 19 (61%) returned for a follow-up coronary CT. RESULTS: Preoperative mean PTH level and CACS were 1,794 +/- 943 pg/mL and 979 +/- 079, respectively; postoperatively, PTH and CACS were 321 +/- 244 pg/mL (P < .001) and 1,285 +/- 1,577 (P = .044), respectively. CACS was stable or reduced (<10% per year) in 6 of 19 patients (32%), and 42% of patients (n = 8) had nearly undetectable (<1% per year) change in CACS after NTPTX. In patients with stable CACS, mean postoperative PTH was 251 versus 516 pg/mL in patients with increasing CACS (P = .02). In patients with recurrent hyperparathyroidism (PTH > 400) compared with patients with stable postoperative PTH, CACS increased by 804 +/- 1082 versus 16 +/- 84 (P = .02). CONCLUSION: Successful NTPTX with stable postoperative PTH levels is associated with stabilization of CACS in patients with severe secondary hyperparathyroidism undergoing hemodialysis, which could contribute to the improved survival seen after NTPTX. PMID- 24238051 TI - Ten percent tall cells confer the aggressive features of the tall cell variant of papillary thyroid carcinoma. AB - BACKGROUND: The tall cell (TC) variant of papillary thyroid carcinoma (PTC) is more aggressive than classic PTC, but the percentage of TC necessary to diagnose this variant has been debated. We aimed to better determine what percentage of TC correlates with a more aggressive phenotype. METHODS: Cases from 2005 to 2010 that were the TC variant of PTC or PTC with TC features were identified and compared with classic PTCs. All cases were reviewed to determine what percent, if any, of the tumors consisted of TC. RESULTS: One hundred forty-one cases of PTC were reviewed. Eighty-three cases had some TC component, and 58 cases had none. There were no differences in patient demographics. Tumors with >=10% TC had more extrathyroidal extension, angiolymphatic invasion, positive surgical margin, and lymph node involvement than classic PTC. There were more recurrences in patients with >=10% TC, but this was not significant. Similar findings were also observed with increasing percentages of TC. CONCLUSION: The aggressive features conferred by the presence of TC in PTCs occur with as little as 10% TC and are maintained with increasing percentages. Therefore, TC in a PTC should be reported if they comprise at least 10% of the tumor. PMID- 24238052 TI - The impact of surgical volume on patient outcomes following thyroid surgery. AB - BACKGROUND: This study aimed to evaluate the effects of indications for thyroidectomy on patient outcomes and to examine the impact of surgical volume on these outcomes. METHODS: The nationwide inpatient sample was used to identify all patients who underwent total thyroidectomy (TT) between 2000 and 2009. We examined the effects of surgeon volume and hospital characteristics on predicting patient outcomes. Univariate and multivariate analyses were used to examine the effects of the indication for surgical care on postoperative outcomes. RESULTS: Overall, 46,261 procedures were identified. Patients with Graves disease had the highest postoperative complications (17.5%) compared to patients undergoing TT for other benign (13.9%) and malignant (13.2%) thyroid disease (P < .001). After stratification by surgeon volume, Graves disease was found to be a significant predictor of postoperative complications in surgeries performed by low- and intermediate-volume surgeons (P < .05). However, Graves disease was not a significant predictor of postoperative complications when performed by high volume surgeons (P = .81). Hospital volume had an inconsistent and marginal protective effect on postoperative outcomes. CONCLUSION: Surgery for Graves disease is associated with a higher risk for complications when performed by less experienced surgeons. This finding should prompt recommendations for increasing surgical specialization and referrals to high-volume surgeons in the management of Graves disease. PMID- 24238053 TI - Effect of reoperation on outcomes in papillary thyroid cancer. AB - BACKGROUND: The influence of lymph node recurrences of papillary thyroid carcinoma (PTC) on overall prognosis is uncertain. We performed a population based, longitudinal analysis to evaluate the impact of reoperation on mortality. METHODS: Patients who underwent initial operation for PTC >1 cm were abstracted from the California Cancer Registry database (1999-2008). Reoperation was defined as any lymph node dissection after total or near-total thyroidectomy. RESULTS: Of the 11,986 patients included in the study, 222 (1.9%) underwent one or more reoperations. The median time to reoperation was 8.7 months, with 58.6% and 83.8% of reoperations being performed within 1 and 2 years of initial thyroidectomy, respectively. The mortality rate from PTC was 2.3% (271 patients). After we adjusted for age, sex, tumor size, stage, and radioactive iodine treatment, we found that reoperation was associated with an increased risk of all-cause mortality in patients >=45 years of age (hazard ratio [HR] 1.51, P < .05). Reoperation was associated with an increased risk of disease-specific mortality in both patients <45 (HR 6.22, P < .01) and >=45 (HR 2.49, P < .001). CONCLUSION: Reoperation is independently associated with mortality in PTC. Most reoperations are performed soon after initial thyroidectomy and likely reflect persistent rather than recurrent disease. PMID- 24238054 TI - A novel optical approach to intraoperative detection of parathyroid glands. AB - BACKGROUND: Inadvertent removal of parathyroid glands is a challenge in endocrine operations. There is a critical need for a diagnostic tool that provides sensitive, real-time parathyroid detection during procedures. We have developed an intraoperative technique using near-infrared (NIR) fluorescence for in vivo, real-time detection of the parathyroid regardless of its pathologic state. METHODS: NIR fluorescence was measured intraoperatively from 45 patients undergoing parathyroidectomy and thyroidectomy. Spectra were measured from the parathyroid and surrounding neck tissues during the operation with the use of a portable, probe-based fluorescence system at 785-nm excitation. Accuracy was evaluated by comparison with histology or visual recognition by the surgeon. RESULTS: NIR fluorescence detected the parathyroid in 100% of patients. Parathyroid fluorescence was stronger (1.2-18 times) than that of the thyroid with peak fluorescence at 822 nm. Surrounding tissues showed no auto fluorescence. Disease state did not affect the ability to discriminate parathyroid glands but may account for signal variability. CONCLUSION: NIR fluorescence spectroscopy can detect intraoperatively the parathyroid regardless of tissue pathology. The signal may be caused by calcium-sensing receptors present in the parathyroid. The signal strength and consistency indicates the simplicity and effectiveness of this method. Its implementation may limit operative time, decrease costs, and improve operative success rates. PMID- 24238055 TI - Development of a calcium-sensing receptor molecular imaging agent. AB - BACKGROUND: Calcium-sensing receptor (CaSR) is expressed by parathyroid cells and thyroid C-cells (from which medullary thyroid carcinoma [MTC] is derived). A molecular imaging agent localizing to the CaSR could improve the detection of parathyroids and MTC preoperatively or intraoperatively. We synthesized a novel compound containing a fluorine residue for potential future labeling and demonstrated that the compound inhibited CaSR function in vitro. METHODS: We synthesized compound M, a derivative of a known calcilytic compound, Calhex-231. Human embryonic kidney cells transfected with green-fluorescent protein-tagged CaSR or control vector were preincubated with compound M before the addition of calcium. Immunoblotting for total mitogen-activated protein kinase (MAPK: ERK1/2), activated MAPK (phosphorylated ERK1/2), and glyceraldehyde 3-phosphate dehydrogenase was performed. RESULTS: Synthesis of compound M was confirmed by mass spectrometry. Inhibition of the MAPK signaling pathway by compound M was demonstrated in a dose-dependent manner by a decrease in phosphorylated ERK1/2 with no change in total ERK1/2 levels. Compound M inhibited MAPK signaling slightly better than the parent compound. CONCLUSION: We have developed a novel molecule which demonstrates functional inhibition of CaSR and has a favorable structure for labeling. This compound appears to be appropriate for further development as a molecular imaging tool to enhance the surgical treatment of parathyroid disease and MTC. PMID- 24238057 TI - Thyroid nodule evaluation: how much is too much? PMID- 24238058 TI - Potential role of 5-aza-2'-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer. AB - BACKGROUND: Melanoma antigen gene family (MAGE)-A4, a member of the cancer testis antigen family, has been reported in various cancers including melanoma, bladder, head and neck, oral, and lung, and is a potential target for T-cell-receptor based immunotherapy. Baseline expression levels of the MAGE-A4 gene in thyroid cancer cell lines have not been previously studied thoroughly. METHODS: Human thyroid cancer cell lines (8505c, HTh7, BCPAP, and TPC-1) were treated with either 10 MUmol/L 5'-azacytidine (Aza) or 10 MUmol/L 5-AZA-2'deoxycytidine (DAC) and evaluated for various MAGEA gene expression. Later melanoma cell lines A375 and 8505c were treated with PLX4720 in combination with DAC and evaluated for MAGE-A4 expression. RESULTS: Only BCPAP cells expressed moderate levels of MAGE A3 and MAGE-A6 at baseline. Treatment with DAC/Aza induced the expression of MAGE A4 and MAGE-A1 in 8505c cells. PLX4720 treatment did not affect MAGE-A4 expression in 8505c cells, but increased its expression in A375 cells. In contrast, addition of PLX4720 to DAC-treated 8505c cells decreased the previously induced MAGE-A4 expression by DAC in these cells. A similar decrease in MAGE-A4 expression by DAC was also seen in 8505cBRAF(-/-) cells. Although DAC treatment resulted in demethylation of the MAGE-A4 promoter in 2 CpG sites, PLX addition to DAC did not affect the demethylation status. CONCLUSION: Demethylating agents increased the expression of MAGE genes in thyroid cancer cells. The effect of BRAFV600E inhibitors on MAGE-A4 expression suggest the role of downstream MEK/BRAF signaling in its expression apart from promoter demethylation being the sole requirement. Expression of MAGE-A4 may make immunotherapeutic intervention possible in selected patients with thyroid cancer. PMID- 24238056 TI - PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target. AB - BACKGROUND: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data for prognostic biomarkers and therapeutic targets. METHODS: We profiled 44 ACC and 4 normal adrenals on Affymetrix U133 Plus 2 expression microarrays. Pathway and transcriptional enrichment analysis was performed. Protein levels were determined by Western blot. Drug efficacy was assessed against ACC cell lines. Previously published expression datasets were analyzed for validation. RESULTS: Pathway enrichment analysis identified marked dysregulation of cyclin dependent kinases and mitosis. Overexpression of PTTG1, which encodes securin, a negative regulator of p53, was identified as a marker of poor survival. Median survival for patients with tumors expressing high PTTG1 levels (log2 ratio of PTTG1 to average beta-actin <-3.04) was 1.8 years compared with 9.0 years if tumors expressed lower levels of PTTG1 (P < .0001). Analysis of a previously published dataset confirmed the association of high PTTG1 expression with a poor prognosis. Treatment of 2 ACC cell lines with vorinostat decreased securin levels and inhibited cell growth (median inhibition concentrations of 1.69 MUmol/L and 0.891 MUmol/L, for SW-13 and H295R, respectively). CONCLUSION: Overexpression of PTTG1 is correlated with poor survival in ACC. PTTG1/securin is a prognostic biomarker and warrants investigation as a therapeutic target. PMID- 24238059 TI - Timing of symptom improvement after parathyroidectomy for primary hyperparathyroidism. AB - BACKGROUND: The timing of symptom improvement after parathyroidectomy for primary hyperparathyroidism (PHPT) has not been well characterized. METHODS: This prospective study involved administering a questionnaire to patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire evaluated the frequency of 18 symptoms of PHPT on a 5-point Likert scale and was administered preoperatively and 1 week, 6 weeks, and 6 months postoperatively. RESULTS: Of 197 eligible patients, 132 (67%) participated in the study. The questionnaires were completed at a rate of 91%, 92%, and 86% at 1 week, 6 weeks, and 6 months postoperatively, respectively. The most commonly reported preoperative symptoms were fatigue (98%), muscle aches (89%), and bone/joint pain (87%). Improvement in symptom severity occurred across all symptoms and was separated into three categories based on the timing of improvement. Fatigue and bone/joint pain demonstrated "Immediate Improvement" (>50% of patients reporting improvement by post-operative week 1), whereas the majority of symptoms showed peak improvement at 6 weeks ("Delayed Improvement"). Symptoms categorized as "Continuous Improvement" were those showing progressive improvement up to 6 months postoperatively (polydipsia, headaches, and nausea/vomiting). CONCLUSION: Symptom improvement was most prominent 6 weeks postparathyroidectomy, although some symptoms showed continued improvement at 6 months. PMID- 24238060 TI - Expansion of endocrine surgery fellowships: if we increase the supply is there demand? PMID- 24238061 TI - Graves' disease and thymic hyperplasia. PMID- 24238062 TI - Mesenchymal progenitor cells in mouse foetal liver regulate differentiation and proliferation of hepatoblasts. AB - BACKGROUND & AIMS: Hepatoblasts are somatic progenitor cells of the foetal liver that possess high proliferative capacity and bi-potency for differentiation into both hepatocytes and cholangiocytes. Although mesenchymal cells are known to be important for liver ontogeny, current understanding of their interaction with hepatoblasts remains obscure. Mesenchymal cell populations in the developing liver were purified and their potential to support proliferation and differentiation of hepatoblasts was examined. METHODS: Foetal liver cells were fractionated with a flow cytometer using antibodies against cell surface markers. Gene expression of mesenchymal-specific transcripts and morphological characteristics were analysed. The ability of the mesenchymal cells to support hepatoblast function was analysed using a transwell and direct coculture system. RESULTS: CD45(-) Ter119(-) CD71(-) Dlk1(mid) PDGFRalpha(+) cells from the mid foetal stage liver expressed the mesenchymal cell-specific transcription factors H2.0-like homeobox 1 and LIM homeobox 2 at high levels. Foetal mesenchymal cells make contact with hepatoblasts in vivo and possess the potential to differentiate into chondrocytes, osteocytes and adipocytes under appropriate cell culture conditions, indicating that these cells are possible candidates for mesenchymal stem/progenitor cells. Foetal mesenchymal cells expressed pleiotrophin, hepatocyte growth factor and midkine 1, which are involved in the growth of hepatoblasts. Using the coculture system with hepatoblasts and foetal mesenchymal cells, these cells were shown to support proliferation and maturation of hepatoblasts through indirect and direct interactions respectively. CONCLUSIONS: Dlk1(mid) PDGFRalpha(+) cells in non-haematopoetic fraction derived from the foetal liver exhibit mesenchymal stem/progenitor cell characteristics and have abilities to support proliferation and differentiation of hepatoblasts. PMID- 24238065 TI - Plaque-type glomuvenous malformations successfully treated using combined pulsed dye laser and neodymium-doped yttrium aluminum garnet laser. PMID- 24238064 TI - The impact of heat on mortality and morbidity in the Greater Metropolitan Sydney Region: a case crossover analysis. AB - BACKGROUND: This study examined the association between unusually high temperature and daily mortality (1997-2007) and hospital admissions (1997-2010) in the Sydney Greater Metropolitan Region (GMR) to assist in the development of targeted health programs designed to minimise the public health impact of extreme heat. METHODS: Sydney GMR was categorized into five climate zones. Heat-events were defined as severe or extreme. Using a time-stratified case-crossover design with a conditional logistic regression model we adjusted for influenza epidemics, public holidays, and climate zone. Odds ratios (OR) and 95% confidence intervals were estimated for associations between daily mortality and hospital admissions with heat-event days compared to non-heat event days for single and three day heat-events. RESULTS: All-cause mortality overall had similar magnitude associations with single day and three day extreme and severe events as did all cardiovascular mortality. Respiratory mortality was associated with single day and three day severe events (95th percentile, lag0: OR = 1.14; 95%CI: 1.04 to 1.24). Diabetes mortality had similar magnitude associations with single day and three day severe events (95th percentile, lag0: OR = 1.22; 95%CI: 1.03 to 1.46) but was not associated with extreme events. Hospital admissions for heat related injuries, dehydration, and other fluid disorders were associated with single day and three day extreme and severe events. Contrary to our findings for mortality, we found inconsistent and sometimes inverse associations for extreme and severe events with cardiovascular disease and respiratory disease hospital admissions. Controlling for air pollutants did not influence the mortality associations but reduced the magnitude of the associations with hospital admissions particularly for ozone and respiratory disease. CONCLUSIONS: Single and three day events of unusually high temperatures in Sydney are associated with similar magnitude increases in mortality and hospital admissions. The trend towards an inverse association between cardio-vascular admissions and heat-events and the strong positive association between cardio-vascular mortality and heat-events suggests these events may lead to a rapid deterioration in persons with existing cardio vascular disease resulting in death. To reduce the adverse effects of high temperatures over multiple days, and less extreme but more frequent temperatures over single days, targeted public health messages are critical. PMID- 24238063 TI - Autophagy maturation associated with CD38-mediated regulation of lysosome function in mouse glomerular podocytes. AB - Podocytes are highly differentiated glomerular epithelial cells that contribute to the glomerular barrier function of kidney. A role for autophagy has been proposed in maintenance of their cellular integrity, but the mechanisms controlling autophagy in podocytes are not clear. The present study tested whether CD38-mediated regulation of lysosome function contributes to autophagic flux or autophagy maturation in podocytes. Podocytes were found to exhibit a high constitutive level of LC3-II, a robust marker of autophagosomes (APs), suggesting a high basal level of autophagic activity. Treatment with the mTOR inhibitor, rapamycin, increased LC3-II and the content of both APs detected by Cyto-ID Green staining and autophagolysosomes (APLs) measured by acridine orange staining and colocalization of LC3 and Lamp1. Lysosome function inhibitor bafilomycin A1 increased APs, but decreased APLs content under both basal and rapamycin-induced conditions. Inhibition of CD38 activity by nicotinamide or silencing of CD38 gene produced the similar effects to that bafilomycin A1 did in podocytes. To explore the possibility that CD38 may control podocyte autophagy through its regulation of lysosome function, the fusion of APs with lysosomes in living podocytes was observed by co-transfection of GFP-LC3B and RFP-Lamp1 expression vectors. A colocalization of GFP-LC3B and RFP-Lamp1 upon stimulation of rapamycin became obvious in transfected podocytes, which could be substantially blocked by nicotinamide, CD38 shRNA, and bafilomycin. Moreover, blockade of the CD38 mediated regulation by PPADS completely abolished rapamycin-induced fusion of APs with lysosomes. These results indicate that CD38 importantly control lysosomal function and influence autophagy at the maturation step in podocytes. PMID- 24238066 TI - Probability of remission of juvenile idiopathic arthritis following treatment with steroid joint injection. AB - OBJECTIVES: Steroid joint injection is indicated as starting treatment for juvenile idiopathic arthritis, but its effect as single treatment has not been explored. Our aim was to estimate arthritis remission probability after single or repeated injections. METHODS: Conduct a retrospective analysis of inactive arthritis status, remission on medication and remission off medication, estimating cumulative probability and mean time to survival, from the first joint injection session to the last follow-up visit or disease-modifying anti-rheumatic drugs initiation. Remission and time to achieve remission status after single or repeated injections were compared. RESULTS: Seventy-seven patients with 4-year medium follow-up and 254 treated joints, were reviewed. Eighty-three percent of the individuals had oligoarticular subtype and 57% had persistent oligoarticular course. Overall, 26% achieved remission off medication status, 4% remission on medication and 38% initiated disease-modifying anti-rheumatic drugs. Survival analysis resulted in mean time of achieving inactive disease status, remission on medication and off medication of 8, 11 and 56 months, respectively. The cumulative probability of remission off medication was 2% at 12 months, 8% at 24 months and 18% at 36 months. Frequency of inactive disease, remission on medication and remission off medication status decreased proportionally following repeated joint injections in comparison with the frequency of the same status for those receiving single treatment. CONCLUSIONS: The dropout rates due to anti rheumatic drugs initiation indicated limited long-term benefits of intra articular steroids for juvenile idiopathic arthritis. PMID- 24238068 TI - Limitations and consumer aspects of point-of-care in snake envenomation. PMID- 24238067 TI - Study protocol: translating and implementing psychosocial interventions in aged home care the lifestyle engagement activity program (LEAP) for life. AB - BACKGROUND: Tailored psychosocial activity-based interventions have been shown to improve mood, behaviour and quality of life for nursing home residents. Occupational therapist delivered activity programs have shown benefits when delivered in home care settings for people with dementia. The primary aim of this study is to evaluate the effect of LEAP (Lifestyle Engagement Activity Program) for Life, a training and practice change program on the engagement of home care clients by care workers. Secondary aims are to evaluate the impact of the program on changes in client mood and behaviour. METHODS/DESIGN: The 12 month LEAP program has three components: 1) engaging site management and care staff in the program; 2) employing a LEAP champion one day a week to support program activities; 3) delivering an evidence-based training program to care staff. Specifically, case managers will be trained and supported to set meaningful social or recreational goals with clients and incorporate these into care plans. Care workers will be trained in and encouraged to practise good communication, promote client independence and choice, and tailor meaningful activities using Montessori principles, reminiscence, music, physical activity and play. LEAP Champions will be given information about theories of organisational change and trained in interpersonal skills required for their role. LEAP will be evaluated in five home care sites including two that service ethnic minority groups. A quasi experimental design will be used with evaluation data collected four times: 6-months prior to program commencement; at the start of the program; and then after 6 and 12 months. Mixed effect models will enable comparison of change in outcomes for the periods before and during the program. The primary outcome measure is client engagement. Secondary outcomes for clients are satisfaction with care, dysphoria/depression, loneliness, apathy and agitation; and work satisfaction for care workers. A process evaluation will also be undertaken. DISCUSSION: LEAP for Life may prove a cost-effective way to improve client engagement and other outcomes in the community setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001064897. PMID- 24238069 TI - Seasonal variation in the behaviour of a short-lived rodent. AB - BACKGROUND: Short lived, iteroparous animals in seasonal environments experience variable social and environmental conditions over their lifetime. Animals can be divided into those with a "young-of-the-year" life history (YY, reproducing and dying in the summer of birth) and an "overwinter" life history (OW, overwintering in a subadult state before reproducing next spring).We investigated how behavioural patterns across the population were affected by season and sex, and whether variation in behaviour reflects the variation in life history patterns of each season. Applications of pace-of-life (POL) theory would suggest that long lived OW animals are shyer in order to increase survival, and YY are bolder in order to increase reproduction. Therefore, we expected that in winter and spring samples, when only OW can be sampled, the animals should be shyer than in summer and autumn, when both OW and YY animals can be sampled.We studied common vole (Microtus arvalis) populations, which express typical, intra-annual density fluctuation. We captured a total of 492 voles at different months over 3 years and examined boldness and activity level with two standardised behavioural experiments. RESULTS: Behavioural variables of the two tests were correlated with each other. Boldness, measured as short latencies in both tests, was extremely high in spring compared to other seasons. Activity level was highest in spring and summer, and higher in males than in females. CONCLUSION: Being bold in laboratory tests may translate into higher risk-taking in nature by being more mobile while seeking out partners or valuable territories. Possible explanations include asset-protection, with OW animals being rather old with low residual reproductive value in spring. Therefore, OW may take higher risks during this season. Offspring born in spring encounter a lower population density and may have higher reproductive value than offspring of later cohorts. A constant connection between life history and animal personality, as suggested by the POL theory, however, was not found. Nevertheless, correlations of traits suggest the existence of animal personalities. In conclusion, complex patterns of population dynamics, seasonal variation in life histories, and variability of behaviour due to asset-protection may cause complex seasonal behavioural dynamics in a population. PMID- 24238070 TI - Editorial for "methods for the isolation and analysis of rare cells". PMID- 24238071 TI - External ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital in Kampala, Uganda. AB - BACKGROUND: Endophthalmitis is a severe complication of cataract surgery which leads to high ocular morbidity and visual loss even with antibiotic treatment. Bacterial ocular floras are the implicated causative agents. This study was undertaken to evaluate the external ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital. METHODS: This cross sectional study enrolled consecutively 131 patients scheduled for routine cataract surgery in the Department of Ophthalmology at Mulago National Hospital in Kampala, Uganda. Eyelid margin and conjunctival swabs were collected and processed using standard microbiological procedures to identify bacterial isolates and their respective antimicrobial susceptibility patterns. RESULTS: Of 131 patients involved (mean age 63.3 +/- 14.5 years), 54.2% (71/131) were females. The eyelid margin and conjunctival samples were culture positive in 59.5% (78/138) and 45.8% (60/138) respectively. The most common organisms identified were Coagulase-negative Staphylococci (CoNS) [65.9% (91/138)] and Staphylococcus aureus [21.0% (29/138)]. CoNS showed the highest resistance to tetracycline (58.2%, 53/91) and erythromycin (38.5%, 35/91), whereas in S. aureus the resistance to tetracycline and erythromycin were 55.2% (16/29) and 31.0% (9/29) respectively. Methicillin resistant CoNS (MRS) and Methicillin resistance S. aureus (MRSA) were 31.9% (29/91) and 27.6% (8/29) respectively. There were low resistance rates for CoNS, S. aureus and other bacterial isolates to ciprofloxacin (11.1%-24.2%), gentamicin (5.6-31.0%), tobramycin (17.2% -25.3%) and vancomycin (0.0%). CONCLUSION: CoNS and S. aureus are the most common bacterial isolates found on the external ocular surface of the pre-operative cataract patients. Ciprofloxacin, gentamicin, tobramycin and vancomycin showed the lowest resistance rates to all bacterial isolates, therefore may be used to reduce bacteria load in the conjunctiva sac among cataract patients prior to surgery. PMID- 24238072 TI - Effects of different mydriatics on intraocular pressure, pupil diameter, and ruminal and intestinal motility in healthy sheep. AB - OBJECTIVE: To determine the effects of the administration of subconjunctival 1% atropine (SA), topical 1% atropine (A), 0.5% tropicamide (T), 1% homatropine (H), 10% phenylephrine (P), and 2% ibopamine (I) on intraocular pressure (IOP), pupil diameter (PD), ruminal motility (RM) and intestinal motility (IM) in sheep. ANIMAL STUDIED: Ten spayed ewes of Santa Ines breed. PROCEDURES: Six experiments were performed separately at 1-week intervals. One eye was randomly selected and received one drop of A, T, H, P, I, or subconjunctival injection of atropine at 8 a.m. On the following days, IOP and PD were evaluated every 8 h until the pupil returned to its normal diameter. Ruminal motility and intestinal motility were evaluated only within the first 13 h. RESULTS: The IOP did not change significantly in the treated eyes compared with the control eyes and baseline at any time point (P > 0.05). A longer-lasting pupil dilation was observed after the administration of A (96 h), SA (79 h), H (24 h), and T (24 h). Within the first 30 min after treatment, RM and IM decreased, by 78% and 82% (H), 76% and 86% (SA), 46% and 58% (A), and 62% and 70% (T) (P < 0.001), respectively, with a tendency to return to baseline values following 13 h of drug administration. Both 10% phenylephrine and 2% ibopamine did not have any effect on the parameters evaluated (P > 0.05). CONCLUSIONS: Topical and subconjunctival 1% atropine, 0.5% tropicamide, and 1% homatropine significantly reduced RM and IM, and induced pupil dilation but did not change IOP in eyes of healthy sheep. The sympathomimetics phenylephrine (10%) and ibopamine (2%) did not change the parameters evaluated. PMID- 24238073 TI - The effects of aromatherapy in relieving symptoms related to job stress among nurses. AB - Workplace-related stress has become today's most serious occupational hazard. Aromatherapy is a simple, convenient and non-invasive method of stress relief. There is little research regarding the efficacy of aromatherapy by means of inhaling essential oil in reducing workplace stress-related symptoms among nurses. Therefore, this study was to examine the effectiveness of lavender oil inhalation in reducing job stress-related symptoms among nurses. The 53 nurses in the experimental group pinned small bottles containing 3% lavender oil on the clothes of their right chests, whereas 57 participants in the control group pinned bottles with no lavender oil. Aromatherapy was shown to be effective in the reduction of the number of stress symptoms for 3 or 4 days. The stress symptoms of the experimental group decreased from 6.1 to 2.8 after aromatherapy was carried out (P = 0.126, 0.159, 0.035 and 0.026). This represented a significant decrease in stress, whereas the stress symptoms in the control group increased from 5.6 to 5.8. Hospital staff managers are still encouraged to include aromatherapy concepts and techniques in the continuing education of nursing staff. Concurrently, future research should focus on the possible side effects of aromatherapy to assure safety. PMID- 24238074 TI - Cerebral blood flow in the neonate. AB - Ensuring adequate oxygenation of the developing brain is the cornerstone of neonatal critical care. Despite decades of clinical research dedicated to this issue of paramount importance, our knowledge and understanding regarding the physiology and pathophysiology of neonatal cerebral blood flow are still rudimentary. This review primarily focuses on currently available human clinical and experimental data on cerebral blood flow and autoregulation in the preterm and term infant. Limitations of systemic blood pressure values as surrogates for monitoring adequate cerebral oxygen delivery are discussed. Particular emphasis is placed on the high interindividual variability in cerebral blood flow values, vasoreactivity, and autoregulatory thresholds making the applications of normative values highly questionable. Technical and ethical difficulties to conduct such trials leave us with a near complete lack of knowledge on how pharmacological and surgical interventions impact on cerebral autoregulation. The ensemble of these works argues for the necessity of highly individualized care by taking advantage of continuous bedside monitoring of cerebral circulation. They also point to the urgent need for further studies addressing the exciting but difficult issue of cerebral blood flow autoregulation in the neonate. PMID- 24238075 TI - Wide circumferential versus individual isolation of pulmonary veins using the endoscopic ablation system. AB - INTRODUCTION: The endoscopic ablation system (EAS) allows for effective pulmonary vein isolation (PVI). The feasibility of wide circumferential as compared to individual PVI using the EAS has not been formally assessed. METHODS: Patients with paroxysmal or short-persistent atrial fibrillation were assigned to individual PVI (group A) or wide circumferential PVI (group B). In group B, circumferential PVI was attempted only if the ipsilateral inferior PV was visualized while the ablation system targeted the superior PV and vice versa. Otherwise, individual PVI was performed. RESULTS: A total of 38 patients were enrolled (Group A: 20 patients, age 61 +/- 7 years, LA-diameter 43 +/- 5 mm; Group B: 18 patients, age 62 +/- 10 years, LA-diameter 43 +/- 4 mm). In group A, 20/20 (100%) right superior (RSPV) and inferior (RIPV) PVs, 18/19 (95%) left superior (LSPV) and inferior (LIPV) PVs, and 1/1 (100%) left common ostium (LCPV) were successfully isolated. First-pass success rate was 95%, 85%, 68%, and 95% for the RSPV, RIPV, LSPV, and LIPV, respectively. Touch-up radiofrequency ablation was required in 1/19 (5%) LSPV and LIPV. In group B, an attempt at circumferential PVI was feasible in 2/18 (11%) septal PVs and successful on first pass. Lateral circumferential PVI was attempted and successful on first-pass in 7/13 (54%) LSPVs and LIPVs and 1/5 (20%) LCPVs. CONCLUSIONS: Using the EAS in patients with AF, separate isolation of individual PVs rather than wide circumferential PVI should be the preferred ablation strategy. PMID- 24238076 TI - Prevalence and related factors of anemia in HAART-naive HIV positive patients at Gondar University Hospital, Northwest Ethiopia. AB - BACKGROUND: Anaemia is a common complication of infection with the human immunodeficiency virus (HIV) and may have various causes. The aim of this study was to determine the prevalence and related factors of anemia in HAART-naive HIV positive Patients. METHODS: A retrospective study was conducted on HAART naive HIV positive patients at the Gondar University Hospital between September 2011 and August 2012. Socio-demographic and immunohematological (hemoglobin and CD4+ T cells) data were collected carefully from the existing ART logbook and patient follow up cards. Anaemia was defined according to the WHO criteria. RESULTS: The overall prevalence of anaemia was 138 (35%). Female HAART naive HIV positive patients had significantly (P < 0.05) higher prevalence of anaemia than males (62% Vs 38%). The prevalence of anaemia at different CD4 level was; 6 (4%) with CD4 count greater than 500 cells/MUL, 18 (13%) with a CD4 count of 350-500 cells/MUL, 37 (27%) with a CD4 count of 200-349 cells/MUL, 44 (32%) with a CD4 count of 100-199 cells/MUL, 14 (10%) with a CD4 count of 50-99 and 19 (14%) with CD4 count of less than 50 cells/MUL. CONCLUSIONS: Our findings showed that one third of HAART naive HIV positive patients were anaemic and the increase in prevalence of anaemia with decreased CD4 cell count was statistically significant. Therefore, early diagnosis and treatment of anaemia in these patients are essential. PMID- 24238077 TI - Exploring hotspots of pneumococcal pneumonia and potential impacts of ejecta dust exposure following the Christchurch earthquakes. AB - The etiology of pneumococcal pneumonia (PP) is well-known. Yet, some events may increase its incidence. Natural disasters may worsen air quality, a risk factor for PP. We investigated spatial/spatio-temporal clustering of PP pre- and post earthquakes in Christchurch, New Zealand. The earthquakes resulted in deaths, widespread damage and liquefaction ejecta (a source of air-borne dust). We tested for clusters and associations with ejecta, using 97 cases (diagnosed 10/2008 12/2011), adjusted for age and area-level deprivation. The strongest evidence to support the potential role of ejecta in clusters of PP cases was the: (1) geographic shift in the spatio-temporal cluster after deprivation adjustment to match the post-earthquake clusters and; (2) increased relative risk in the fully adjusted post-earthquake compared to the pre-earthquake cluster. The application of spatial statistics to study PP and ejecta are novel. Further studies to assess the long-term impacts of ejecta inhalation are recommended particularly in Christchurch, where seismic activity continues. PMID- 24238078 TI - How to choose geographical units in ecological studies: proposal and application to campylobacteriosis. AB - In spatial epidemiology, the choice of an appropriate geographical unit of analysis is a key decision that will influence most aspects of the study. In this study, we proposed and applied a set of measurable criteria applicable for orienting the choice of geographical unit. Nine criteria were selected, covering many aspects such as biological relevance, communicability of results, ease of data access, distribution of exposure variables, cases and population, and shape of unit. These criteria were then applied to compare various geographical units derived from administrative, health services, and natural frameworks that could be used for the study of the spatial distribution of campylobacteriosis in the province of Quebec, Canada. In this study, municipality was the geographical unit that performed the best according to our assessment and given the specific objectives and time period of the study. Future research areas for optimizing the choice of geographical unit are discussed. PMID- 24238080 TI - Why computational models are better than verbal theories: the case of nonword repetition. AB - Tests of nonword repetition (NWR) have often been used to examine children's phonological knowledge and word learning abilities. However, theories of NWR primarily explain performance either in terms of phonological working memory or long-term knowledge, with little consideration of how these processes interact. One theoretical account that focuses specifically on the interaction between short-term and long-term memory is the chunking hypothesis. Chunking occurs because of repeated exposure to meaningful stimulus items, resulting in the items becoming grouped (or chunked); once chunked, the items can be represented in short-term memory using one chunk rather than one chunk per item. We tested several predictions of the chunking hypothesis by presenting 5-6-year-old children with three tests of NWR that were either high, medium, or low in wordlikeness. The results did not show strong support for the chunking hypothesis, suggesting that chunking fails to fully explain children's NWR behavior. However, simulations using a computational implementation of chunking (namely CLASSIC, or Chunking Lexical And Sub-lexical Sequences In Children) show that, when the linguistic input to 5-6-year-old children is estimated in a reasonable way, the children's data are matched across all three NWR tests. These results have three implications for the field: (a) a chunking account can explain key NWR phenomena in 5-6-year-old children; (b) tests of chunking accounts require a detailed specification both of the chunking mechanism itself and of the input on which the chunking mechanism operates; and (c) verbal theories emphasizing the role of long-term knowledge (such as chunking) are not precise enough to make detailed predictions about experimental data, but computational implementations of the theories can bridge the gap. PMID- 24238079 TI - Estimation of malaria incidence in northern Namibia in 2009 using Bayesian conditional-autoregressive spatial-temporal models. AB - As malaria transmission declines, it becomes increasingly important to monitor changes in malaria incidence rather than prevalence. Here, a spatio-temporal model was used to identify constituencies with high malaria incidence to guide malaria control. Malaria cases were assembled across all age groups along with several environmental covariates. A Bayesian conditional-autoregressive model was used to model the spatial and temporal variation of incidence after adjusting for test positivity rates and health facility utilisation. Of the 144,744 malaria cases recorded in Namibia in 2009, 134,851 were suspected and 9893 were parasitologically confirmed. The mean annual incidence based on the Bayesian model predictions was 13 cases per 1000 population with the highest incidence predicted for constituencies bordering Angola and Zambia. The smoothed maps of incidence highlight trends in disease incidence. For Namibia, the 2009 maps provide a baseline for monitoring the targets of pre-elimination. PMID- 24238081 TI - Serologic markers for HBV, HCV and HIV in immigrants visiting the Athens' polyclinic of 'Doctors of the World - Greece'. PMID- 24238082 TI - Ageism in nursing. AB - AIM: Ageism in health care delivery and nursing poses a fundamental threat to health and society. In this commentary, implications of age discrimination are presented to generate an agenda for action in nursing management. BACKGROUND: In nations like the United States and the United Kingdom, nursing is an ageing profession caring for an ageing society where age discrimination takes many forms and has broad impact. EVALUATION: This commentary critically synthesizes the literature on ageism and relevant data on ageing societies for nurse managers and other leaders. KEY ISSUES: Investigations of ageism suggest that discrimination negatively affects health and results in poor health care experiences. Age discrimination is present in nursing, exacerbating workforce shortages and limiting the use of expertise within the profession. CONCLUSION: Nursing faces a future for which understanding ageing societies and ageism is essential. An agenda for the future is proposed. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers possess the power to enact an agenda for combating ageism in health care and nursing. PMID- 24238083 TI - Research on clinical decision making: challenges for professional disciplines. PMID- 24238084 TI - Barriers to colorectal cancer screening in Hispanics in the United States: an integrative review. AB - Colorectal cancer (CRC) is one of the leading cancer killers in the U.S. despite the vast array of screening and detection methods available. The U.S. Hispanic population, in particular, reflects low rates of CRC screening. In order to get a comprehensive understanding of barriers to CRC screening in this population, an integrative review was performed in PubMed and CINAHL from 2002 to 2012; eight studies on various barriers to CRC screening among the U.S. Hispanic population were examined. Our findings recognized fear, cost, and lack of awareness as common barriers to CRC screening and more specific barriers applicable to the Hispanic population being low literacy/educational levels and lack of provider recommendations. Analysis indicated culturally-specific barriers to CRC screening among Hispanics, the largest being limited English proficiency. The review demonstrated a need for additional targeted approaches, awareness education, and provider training as ways to increase CRC screening in Hispanics. PMID- 24238085 TI - Effectiveness of nurse-delivered patient education interventions on quality of life in outpatients: a systematic review. AB - BACKGROUND: Nursing education is a crucial part of nursing practice; however, evidence regarding its impact on quality of life is lacking. No review has addressed the effects of overall nursing education interventions on the quality of life in a general outpatient population. OBJECTIVES: The objective of this study is to evaluate the effectiveness of nurse-delivered education interventions compared with usual care with regard to the quality of life of outpatients. METHODS: A systematic search was performed to identify randomized controlled trials that examined the effects of nurse-delivered educational interventions on the quality of life of outpatients. The search was performed in December 2012 in the MEDLINE (via PubMed), EMBASE (via Ovid), and CINAHL (via EBSCO) databases and was limited with regard to publication time and language. The studies were appraised according to methodological quality, and p values were extracted to determine the effectiveness of the interventions. RESULTS: Twenty-nine studies were included in the review. Approximately 70% of the studies included showed no effects on quality of life. The studies that showed positive effects each used different types of interventions. A methodological appraisal revealed biases in most of the studies. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Because of an overall lack of effectiveness and heterogeneity between studies, no evidence for the effectiveness of nursing education interventions in outpatients was observed. Further studies should examine interventions that focus on quality of life using validated measures. PMID- 24238086 TI - Disaster evacuation for persons with special needs: a content analysis of information on YouTube. AB - Disaster preparedness is more complex for persons with chronic illness, who may require specific planning to address unique needs. Research suggests that advance preparation and evacuation during a disaster leads to better health outcomes. Individuals access, and rely on, health information via online sources. The purpose of this descriptive qualitative study was to examine information that persons who may have special needs receive from an Internet based free sharing source, YouTube, related to disaster evacuation procedures. A content analysis of 51 clips using the Health Literacy Skills Framework revealed themes related to quality and region. Findings suggested concerns such as errors, minimal information about management of conditions during evacuation, and lack of diversity. PMID- 24238087 TI - Causes of mortality and pathological lesions observed post-mortem in red squirrels (Sciurus vulgaris) in Great Britain. AB - BACKGROUND: The red squirrel population in Great Britain has declined dramatically in recent decades, principally due to squirrelpox. Concern exists that red squirrels may become extinct nationally and, as there has been limited research in to diseases other than squirrelpox, this study aimed to identify additional causes of mortality. RESULTS: Post-mortem examinations on 163 red squirrels found dead on Isle of Wight (IoW) England, in Scotland and at other locations in Great Britain showed that 41.7% (n = 68) were killed by road traffic and 9.2% (n = 15) by predators, principally domestic cats and dogs. The overall male/female ratio was 1.08/1. Fleas were recorded on 34.9% of IoW squirrels and on 43.8% of Scottish squirrels but sucking lice and ixodid ticks were only seen on Scottish squirrels. Bacterial infections were significant, particularly in association with respiratory disease (n = 16); two squirrels died of Bordetella bronchiseptica bronchopneumonia. Cases of fatal exudative dermatitis (n = 5) associated with a lukM-positive clone of Staphylococcus aureus occurred only on the IoW. Toxoplasmosis (n = 12) was also confined to IoW where it was responsible for almost one tenth (9.5%) of all deaths. Hepatozoonosis was common, especially in IoW squirrels, but was not considered a primary cause of mortality. Hepatic capillariasis affected four IoW squirrels and one from Scotland. Fungal infections included oral candidiasis, adiaspiromycosis and pulmonary phaeohyphomycosis. Neoplastic conditions diagnosed were: pulmonary carcinoma, gastric spindle cell tumour, renal papillary adenoma and trichoepithelioma. Epidermal hyperplasia of unknown aetiology was seen in squirrels showing crusty lesions of the ear pinnae on IoW (n = 3) and Brownsea Island (n = 1), associated in two cases with cutaneous wart-like growths. Miscellaneous diagnoses included chylothorax, electrocution, intussusception, suspected cholecalciferol rodenticide poisoning and foetal death and mummification. No cases of squirrelpox were diagnosed. CONCLUSIONS: Red squirrels in Britain suffer premature or unnatural mortality due to a number of conditions in addition to squirrelpox, many of which result, directly or indirectly, from human activities: road traffic trauma, pet predation, toxoplasmosis, trap injuries, rodenticide poisoning and electrocution accounted for 61% of all recorded mortality in this study. Red squirrels are also affected by several diseases of unknown aetiology which merit further research. PMID- 24238089 TI - Convergent evidence of brain overconnectivity in children with autism? AB - In this issue of Cell Reports, Keown et al. and Supekar et al. report widespread increases in brain connectivity in children with autism. These studies challenge the widely established theory of underconnectivity in autism, suggesting a more complicated picture of brain connectivity alterations. PMID- 24238088 TI - Cyclophilin A from Schistosoma japonicum promotes a Th2 response in mice. AB - BACKGROUND: Schistosomiasis is a chronic infection, where the host immune response to the parasite changes from a predominantly Th1 to Th2 phenotype, when parasite enters the egg stage, restraining the host inflammatory immune responses to achieve a longer survival in the host. On the other hand, the development of Th2 responses causes immunopathological changes such as liver fibrosis. Therefore identification of schistosome-derived Th2 inducing molecules is important in the understanding of pathogenesis of schistosomiasis. A cyclophilin A homologue of Schistosoma japonicum was reported to be an egg-stage specific antigen, but its immunogenicity and immunoregulatory activities remain unknown. METHODS: We cloned and expressed the gene of cyclophilin A from Schistosoma japonicum (AY814078), named as SjCyP18 based on its molecular weight. The expression profiles in different stages of S. japonicum were examined by RT-PCR and immunofluorescence assay. The immunogenicity of SjCyP18 was measured by the presence of IgG in the sera from S. japonicum infected patients and animals, and the Th2-promting activities were examined by the subclass of immunoglobulins against SjCyP18 and by the IL-4 induction in T cells following footpad injection of SjCyP18. RESULTS: The cloned SjCyP18 has 65% homology with human or mouse cyclophilin A at the amino acid level. In contrast to reports as an egg-stage specific antigen, the gene was found to be expressed in all stages of S. japonicum. IgG responses against SjCyP18 were found in some S. japonicum infected patients and were significantly induced when infection become patent and produce eggs in infected mice. Furthermore, the Th2-promoting subclass of IgG1 was the predominant isotype in S. japonicum infected mice. More importantly, footpad injection of SjCyP18 induced a greater production of IL-4 than that of IFN-gamma by lymphocytes compared to responses from PBS injection controls. CONCLUSION: The cyclophilin A homologue found in S. japonicum is immunogenic and promotes Th2 responses in vivo which may contribute to the establishment of chronic infection by schistosomes. PMID- 24238090 TI - Cerebral babesiosis and acute respiratory distress syndrome in a dog. AB - OBJECTIVE: To describe a case of cerebral babesiosis and acute respiratory distress syndrome (ARDS) in a dog. CASE SUMMARY: A 5-year-old male neutered Scottish Terrier was referred to the emergency department of the Ecole Nationale Veterinaire de Toulouse for evaluation of progressive dyspnea and clinical signs suggestive of central neurological disease. Thoracic radiographs showed a diffuse and heavy interstitial/alveolar lung pattern. Babesiosis was diagnosed based on blood smear evaluation. The dog died of cardiopulmonary arrest 6 hours after presentation. Cerebral babesiosis and ARDS were confirmed at necropsy. Major pathological findings included erythrocyte aggregation in the lungs, liver, and brain. NEW OR UNIQUE INFORMATION PROVIDED: This case report describes an unusual clinical presentation of Babesia canis canis infection, the most common species associated with babesiosis in Europe. In addition, this is to our knowledge the first case of Babesia-associated ARDS confirmed by histopathology in a dog. PMID- 24238091 TI - Noncosmetic skin-related procedures performed in the United States: an analysis of national ambulatory medical care survey data from 1995 to 2010. AB - BACKGROUND: Demand for dermatologic care is increasing alongside a known shortage of physicians in the dermatology workforce. Changes in the volume of dermatologic procedures over time and the physician specialties involved in skin-related procedural care are not well characterized. OBJECTIVE: To determine the frequency of dermatologic procedures performed in the United States between 1995 and 2010 and to analyze the changes in the procedures and physicians performing procedures over time. METHODS: The annual volume of skin-related procedures performed by physician specialties and the rate of procedures performed per physician was determined from data from the National Ambulatory Medical Care Survey (NAMCS) between 1995 to 2004 and 2007 to 2010. RESULTS: Dermatologists and primary care physicians performed most procedures (54.7% and 19.5%, respectively). CONCLUSIONS: Dermatologists perform a larger volume of procedures than in the past, although the proportion of procedures performed by dermatologists is unchanged, and other physician specialties are performing more skin-related procedures to meet increasing demand. PMID- 24238093 TI - Long-term evaluation of antimalarials in a Dutch SLE cohort: intolerance and other reasons for non-use. AB - OBJECTIVES: Antimalarials (AMs) have been demonstrated to reduce disease activity and prevent damage accrual in SLE. Recent guidelines advise prescribing AMs in all patients with SLE. We present data from the Amsterdam Lupus Cohort on use, reasons for non-use, and dosage related intolerance of AMs, as well as disease related variables associated with non-use. METHODS: AM use was assessed in all our SLE patients included in a longitudinal cohort study. Demographic and disease characteristics were compared between users and non-users of AMs. Daily dosages of hydroxychloroquine (HCQ) according to lean body weight were calculated. RESULTS: Out of 190 SLE patients in the cohort, 139 (73.2%) were using AMs during their last visit, predominantly HCQ (136/139, 97.8%), while 92.1% (175/190) had ever used AMs. Daily dosage of HCQ was 400 mg in 115/136 (84.6%) patients. According to lean body weight, 119/136 (87.5%) had daily dosages of HCQ above the recommended 6.5 mg/kg. Patients did not use AMs (n=51) for the following reasons: intolerance (n=16), discontinued without a documented reason (n=11), never initiated (n=9), quiescent disease (n=7), contraindication (n=2), other (n=6). Only one patient discontinued HCQ due to AM-related retinopathy. Non-use of AMs was associated with a longer disease duration, higher damage accrual and a history of lupus nephritis. CONCLUSIONS: Despite increased awareness of the importance of AM treatment in SLE, there is still room for improvement, especially in patients with lupus nephritis and/or long-standing disease. Daily dosages of hydroxychloroquine often exceeded recommendations from guidelines, but are generally well-tolerated. PMID- 24238092 TI - New phylogenomic data support the monophyly of Lophophorata and an Ectoproct Phoronid clade and indicate that Polyzoa and Kryptrochozoa are caused by systematic bias. AB - BACKGROUND: Within the complex metazoan phylogeny, the relationships of the three lophophorate lineages, ectoprocts, brachiopods and phoronids, are particularly elusive. To shed further light on this issue, we present phylogenomic analyses of 196 genes from 58 bilaterian taxa, paying particular attention to the influence of compositional heterogeneity. RESULTS: The phylogenetic analyses strongly support the monophyly of Lophophorata and a sister-group relationship between Ectoprocta and Phoronida. Our results contrast previous findings based on rDNA sequences and phylogenomic datasets which supported monophyletic Polyzoa (= Bryozoa sensu lato) including Ectoprocta, Entoprocta and Cycliophora, Brachiozoa including Brachiopoda and Phoronida as well as Kryptrochozoa including Brachiopoda, Phoronida and Nemertea, thus rendering Lophophorata polyphyletic. Our attempts to identify the causes for the conflicting results revealed that Polyzoa, Brachiozoa and Kryptrochozoa are supported by character subsets with deviating amino acid compositions, whereas there is no indication for compositional heterogeneity in the character subsets supporting the monophyly of Lophophorata. CONCLUSION: Our results indicate that the support for Polyzoa, Brachiozoa and Kryptrochozoa gathered so far is likely an artifact caused by compositional bias. The monophyly of Lophophorata implies that the horseshoe shaped mesosomal lophophore, the tentacular feeding apparatus of ectoprocts, phoronids and brachiopods is, indeed, a synapomorphy of the lophophorate lineages. The same may apply to radial cleavage. However, among phoronids also spiral cleavage is known. This suggests that the cleavage pattern is highly plastic and has changed several times within lophophorates. The sister group relationship of ectoprocts and phoronids is in accordance with the interpretation of the eversion of a ventral invagination at the beginning of metamorphosis as a common derived feature of these taxa. PMID- 24238095 TI - From the Editor's perspective.... PMID- 24238094 TI - Dovitinib induces mitotic defects and activates the G2 DNA damage checkpoint. AB - Dovitinib (TKI258; formerly CHIR-258) is an orally bioavailable inhibitor of multiple receptor tyrosine kinases. Interestingly, Dovitinib triggered a G2 /M arrest in cancer cell lines from diverse origins including HeLa, nasopharyngeal carcinoma, and hepatocellular carcinoma. Single-cell analysis revealed that Dovitinib promoted a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induced a G2 arrest similar to the G2 DNA damage checkpoint. In support of this, DNA damage was triggered by Dovitinib as revealed by gamma-H2AX and comet assays. The mitotic kinase CDK1 was found to be inactivated by phosphorylation in the presence of Dovitinib. Furthermore, the G2 arrest could be overcome by abrogation of the G2 DNA damage checkpoint using small molecule inhibitors of CHK1 and WEE1. Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP ribose) polymerases. These results are consistent with the recent finding that Dovitinib can also target topoisomerases. Collectively, these results suggest additional directions for use of Dovitinib, in particular with agents that target the DNA damage checkpoint. PMID- 24238096 TI - Educational outreach visits to improve nurses' use of mechanical venous thromboembolism prevention in hospitalized medical patients. AB - Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized medical patients. Evidence-based guidelines exist for preventing VTE; unfortunately, these guidelines are not always adhered to by clinicians. The aim of this study was to evaluate the acceptability, utility and clinical impact of an educational outreach visit (EOV) on nurses' provision of mechanical prophylaxis to hospitalized medical patients using a prospective, uncontrolled, before-and-after design. Nurses received a 1-to-1 educational session on mechanical VTE prevention by a trained nurse facilitator. The EOV intervention was designed by a multidisciplinary group of healthcare professionals using social marketing theory. Eighty-five of the 120 eligible nurses (71%) attended the EOV. The median length of each visit was 11.5 minutes (interquartile range [IQR], 10-15) and the median time spent arranging and conducting each visit was 63 minutes (IQR, 49-85). Eighty-four (99%) of the 85 participants gave a verbal commitment to trial the new evidence-based mechanical VTE prevention practices. However, there were no measurable improvements in the proportion of patients risk assessed (-1.7% improvement; 95% confidence interval [CI], -7.0 to 10.3; P = .68) or provided appropriate mechanical prophylaxis (-0.3% improvement; 95% CI, -13.4 to 14; P = .96). Researchers conclude that EOV should not be used to improve nurses' use of mechanical VTE prevention because it has no measurable impact on clinical practice and is resource intensive, requiring 4.5 minutes of preparation for every minute spent face to face with participants. Further research into the specific mechanism of action is required to explain the variability in clinical effect seen with this intervention. PMID- 24238097 TI - Improving glycemic control in the acute care setting through nurse education. AB - Patients with a primary or secondary diagnosis of diabetes present unique challenges during an inpatient hospital stay to treat an acute or chronic illness. Upon review of current hospital practice, an interprofessional team embarked on a performance improvement project to improve outcomes for the complex medical-surgical diabetic patient. The methods detailed herein--a comprehensive education plan, preceptorship and peer accountability, active engagement and support by the unit nursing leadership team, and interprofessional collaboration- offer strategies any organization can implement to positively impact diabetes care. PMID- 24238098 TI - Patients' experiences and feelings before undergoing peripheral percutaneous transluminal angioplasty. AB - The use of interventional radiology as treatment has increased dramatically and peripheral arterial disease (PAD) is now a common indication for vascular interventions such as percutaneous transluminal angioplasty (PTA).(1) PAD seriously impairs quality of life, and patients experience a lack of control over the disease. The aim of this study was to identify patients who are predominantly anxious or calm before PTA treatment and to explore reasons for these feelings. The study includes both individual interviews, a shortened version of a Swedish Mood Adjective Check List (MACL), and an overall assessment of the perceived degree of calmness-anxiety. Forty-two patients were included in the study. The 'anxious' group showed a significantly lower mood in all scales of the MACL compared with the 'calm' group. Reasons for feeling calm were a sense of being safe and high expectations. Reasons for feeling anxious were represented by a sense of despair and apprehension about the PTA. The main reason for feeling calm was related to trust in their caregivers and an ability to foresee upcoming events. The main reason for feeling anxious before the PTA was fear of a negative outcome and being unsure of treatment options. Greater knowledge and a better understanding of their disease and treatment options would support patients' ability to accept reasons for waiting before using invasive treatment. Moreover, this could decrease their anxiety and increase their feeling of being in control of their situation. PMID- 24238099 TI - Ultrasound-guided thrombin injection for treatment of iatrogenic femoral pseudo aneurysm: a nursing protocol. AB - Femoral pseudo-aneurysm (FPA) is a pulsatile hematoma (false aneurysm) of the femoral artery that communicates with an artery through a disruption in the arterial wall. Most often, FPA develops after an injury or angiographic access to the femoral artery with bleeding into the adjacent tissue. FPA is an uncommon complication, but a very significant one, that can have serious consequences. FPA can initially present as a new thrill or bruit, a pulsatile hematoma, or marked pain and tenderness near the site of arterial puncture. Doppler flow imaging has been the mainstay of diagnosis. Ultrasound (US)-guided compression was the treatment of choice. However, it carries drawbacks including length of time to compress for adequate closure of the artery, discomfort to patients, high recurrence rate in patients receiving anticoagulation, femoral artery thrombosis, and a success rate of only 75% overall. An alternative to compression is US guided thrombin injection (UGTI) of the FPA. This is a safe procedure that can be done as an outpatient or in an office setting. This paper will provide nursing guidelines and rationale as well as a nursing protocol for the management of patients who undergo UGTI for FPA. PMID- 24238100 TI - Review of an article: Protamine does not increase risk of stroke in patients with elective carotid stenting by Jennifer S. McDonald, PhD; David F. Kallmes, MD; Giuseppe Lanzino, MD; Harry J. Cloft, MD, PhD (Stroke 2013;44:2028-30). PMID- 24238101 TI - Probiotics for infantile colic: a systematic review. AB - BACKGROUND: Infantile colic is a common paediatric condition which causes significant parental distress. Increased intestinal coliform colonization in addition to alteration in Lactobacillus abundance and distribution may play an important role in its pathogenesis. The objectives of this systematic review are to evaluate the efficacy of probiotic supplementation in the reduction of crying time and successful treatment of infantile colic. METHODS: Literature searches were conducted of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Only randomized controlled trials enrolling term, healthy infants with colic were included. A meta-analysis of included trials was performed utilizing the Cochrane Collaboration methodology. RESULTS: Three trials that enrolled 220 breastfed infants met inclusion criteria, of which 209 infants were available for analysis. Two of the studies were assessed as good quality. Lactobacillus reuteri (strains-American Type Culture Collection Strain 55730 and DSM 17 938) was the only species utilized in the therapeutic intervention. Two of the trials were industry funded. Probiotic supplementation compared to simethicone or placebo significantly and progressively shortened crying times to 7 days reaching a plateau at three weeks post initiation of therapy [mean difference -56.03 minutes; 95% CI (-59.92, -52.15)]. Similarly, probiotics compared to placebo significantly increased the treatment success of infantile colic with a relative risk (RR) of 0.06; 95% CI (0.01, 0.25) and a number needed to treat of 2. CONCLUSIONS: Although L. reuteri may be effective as a treatment strategy for crying in exclusively breastfed infants with colic, the evidence supporting probiotic use for the treatment of infant colic or crying in formula-fed infants remains unresolved. Results from larger rigorously designed studies will help draw more definitive conclusions. PMID- 24238103 TI - Ocular findings and reference values for selected ophthalmic diagnostic tests in the macaroni penguin (Eudyptes chrysolophus) and southern rockhopper penguin (Eudyptes chrysocome). AB - OBJECTIVE: To describe ophthalmic examination findings and standard diagnostic test results in 2 penguin species. ANIMALS STUDIED: Macaroni & Southern Rockhopper Penguins. PROCEDURE: Complete ophthalmic examinations including Schirmer tear test (STT), modified phenol red thread test (PTT), tonometry, and echobiometry were performed on penguins housed at the Detroit Zoo. Mean and standard deviation of ophthalmic tests are reported and compared for significance using two sample t-tests with significance set at P < 0.05. Correlations between variables were assessed using Pearson's correlation coefficient. RESULTS: Cataracts were the most common finding, present in 64% of Macaroni Penguins, and 68% of Rockhopper Penguins. There were anterior segment anomalies in all eyes with cataracts consistent with lens-induced uveitis. The mean modified PTT for the Macaronis was 24.7 +/- 6.37 mm/15 s and 25.1 +/- 7.07 mm/15 s in the Rockhoppers. The mean STT value for the Macaronis was 12.1 +/- 5.43 mm/min and 11.0 +/- 3.96 mm/min in the Rockhoppers. Mean intraocular pressure (IOP) for the Macaronis was 21.9 +/- 7.05 mmHg measured by applanation tonometry and 29.1 +/- 7.16 mmHg using rebound tonometry. The Rockhoppers had a mean IOP of 20.0 +/- 5.77 mmHg and 24.1 +/- 5.09 mmHg for applanation and rebound tonometry, respectively. In both populations, there was a significant difference in IOP measurement between the two instruments. In the Macaroni penguins, the presence of cataracts correlated significantly with increased age and lower IOP readings. Anterior chamber distance and axial globe length were significantly greater in males than in females in both penguin species. PMID- 24238102 TI - Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer. AB - BACKGROUND: Ovarian cancer is characterized by high rates of metastasis and therapeutic resistance. Many chemotherapeutic agents rely on the induction of oxidative stress to cause cancer cell death, thus targeting redox regulation is a promising strategy to overcome drug resistance. METHODS: We have used a tetracycline-inducible Ets-1 overexpression model derived from 2008 ovarian cancer cells in the present study. To examine the role of Ets-1 in glutathione regulation we have measured intracellular reactive oxygen species and glutathione levels, as well as glutathione peroxidase enzyme activity. Glutathione synthesis was limited using transsulfuration or Sx(c)- pathway blocking agents, and glutamate release was measured to confirm Sx(c)- blockade. Cell viability following drug treatment was assessed via crystal violet assay. Oxidative stress was induced through glucose oxidase treatment, which produces hydrogen peroxide by glucose oxidation. The protein expressions of redox-related factors were measured through western blotting. RESULTS: Overexpression of Ets-1 was associated with decreased intracellular ROS, concomitantly with increased intracellular GSH, GPX antioxidant activity, and Sx(c)- transporter activity. Under basal conditions, inhibition of the transsulfuration pathway resulted in decreased GSH levels and GPX activity in all cell lines, whereas inhibition of Sx(c)- by sulfasalazine decreased GPX activity in Ets-1-expressing cells only. However, under oxidative stress the intracellular GSH levels decreased significantly in correlation with increased Ets-1 expression following sulfasalazine treatment. CONCLUSIONS: In this study we have identified a role for proto-oncogene Ets-1 in the regulation of intracellular glutathione levels, and examined the effects of the anti-inflammatory drug sulfasalazine on glutathione depletion using an ovarian cancer cell model. The findings from this study show that Ets-1 mediates enhanced Sx(c)- activity to increase glutathione levels under oxidative stress, suggesting that Ets-1 could be a promising putative target to enhance conventional therapeutic strategies. PMID- 24238104 TI - Web-based self-management with and without coaching for type 2 diabetes patients in primary care: design of a randomized controlled trial. AB - BACKGROUND: Self-management is recognized as the cornerstone of overall diabetes management. Web-based self-management programs have the potential of supporting type 2 diabetes patients with managing their diabetes and reducing the workload for the care provider, where the addition of online coaching could improve patient motivation and reduce program attrition. This study aims to test the hypothesis that a web-based self-management program with coaching will prove more effective on improving patient self-management behavior and clinical outcome measures than a web-based self-management program without coaching. METHODS: The effects of a web-based self-management program with and without coaching will be tested with a nested randomized controlled trial within a healthcare group in the Netherlands. In one year 220 type 2 diabetes patients will be randomized into an intervention group (n = 110) or a control group (n = 110). The control group will receive only the online self-management program. The intervention group will receive the online self-management program and additional online coaching. Participants will be followed for one year, with follow-up measurements at 6 and 12 months. DISCUSSION: The intervention being tested is set to support type 2 diabetes patients with their diabetes self-management and is expected to have beneficial effects on self-care activities, well being and clinical outcomes. When proven effective this self-management support program could be offered to other health care groups and their type 2 diabetes patients in the Netherlands. TRIAL REGISTRATION: Nederlands Trial Register NTR4064. PMID- 24238105 TI - The relationship between head and neck position and endotracheal tube intracuff pressure in the pediatric population. AB - BACKGROUND: Over the past few years, there has been a change in clinical practice with a transition to the use of cuffed instead of uncuffed endotracheal tubes (ETTs) in pediatric patients. These changes have led to concerns regarding unsafe intracuff pressures in pediatric patients, which may result in postoperative morbidity. To avoid these issues, it is generally suggested that the intracuff pressure be maintained at <=30 cmH2 O. The current study prospectively assesses the changes in intracuff pressure related to alterations in head and neck position in pediatric patients. METHODS: Patients less than 18 years of age, undergoing surgery, requiring endotracheal intubation with a cuffed ETT were eligible for inclusion. No alteration in the technique of anesthetic induction or maintenance was required for the study. Following endotracheal intubation and inflation of the cuff with the head and neck in a neutral position, the intracuff pressure was measured. The intracuff pressure was then subsequently measured with the head turned to the right, head turned to the left, head and neck flexed, and head and neck extended. RESULTS: A total of 200 patients were included in the study resulting in a total of 1000 intracuff pressure readings. When compared to the neutral position, the intracuff pressure increased in 545 instances (68.1%) with changes in position of the head and neck. An increase in intracuff pressure was noted more frequently and to the greatest degree with head and neck flexion. The pressure decreased in 153 instances (19.1%), most frequently with neck extension. CONCLUSION: Significant changes in the intracuff pressure occur with changes in head and neck position. In several cases, this resulted in a significant increase in the intracuff pressure. For prolonged cases with the head and neck turned from the neutral position, the intracuff pressure should be measured following patient positioning to ensure that the intracuff pressure is within the clinically recommended range. PMID- 24238106 TI - The American Journal of Reproductive Immunology: last printed issue. PMID- 24238107 TI - Intravenous immunoglobulin treatment for repeated IVF/ICSI failure and unexplained infertility: a systematic review and a meta-analysis. AB - Intravenous immunoglobulin (IVIG) has been introduced empirically into IVF/ICSI programs with the hopes of improving in vitro fertilization (IVF) success. However, the effects of IVIG have been inconsistent. We investigated the effects of IVIG on hard outcomes, including implantation rate, clinical pregnancy rate, live birth rate, miscarriage rate, and live birth rate per embryo transferred. The PubMed, EMBASE, and CNKI databases were searched up to June of 2013 and 10 studies were included. Case-controlled studies comparing IVIG with placebo in IVF/ICSI women and/or unexplained infertility were included. Using fixed and random effects models, the pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated. The use of IVIG was significantly associated with a higher implantation rate and RR was 2.708 (95%CI: 1.302-5.629) compared with the placebo. The clinical pregnancy rate and the live birth rate were significantly increased in patients randomized to IVIG; RR was 1.475 (95%CI: 1.191-1.825) for the clinical pregnancy rate and RR was 1.616 (95%CI: 1.243-2.101) for the live birth rate. Moreover, the miscarriage rate was significantly less in patients randomized to IVIG (0.352, 95%CI: 0.168-0.738), but the live birthrate per embryo transferred was not (2.893; 95%CI: 0.810-10.331) less. Our results strongly support that IVIG is a useful treatment option for women undergoing repeated IVF failure. PMID- 24238109 TI - [Epidemiology of laryngeal and hypopharyngeal cancer in the period 1988-2012 in the material of the Otolaryngology Clinic of the Bialystok Medical University]. AB - Malignant tumour is the second cause of death in Poland, behind cardiovascular disease. 26% of men and 23% of women die of it. Head and neck tumours are the fifth most frequent group of malignant tumours. These are mostly squamous cell carcinomas. The carcinogenic factors of tobacco smoke play an indisputable role in the pathogenesis of these tumours. AIM OF WORK: Analysis comprising: number of patients, sex and age, site and stage of the primary tumour (T), clinical assessment of neck lymph nodes (N). The results underwent statistical analysis. MATERIALS AND METHODS: The study involved 1313 patients who underwent surgery in the period 1988-2012 in the Otolaryngology Clinic in Bialystok (1199 men and 114 women, aged 32-86 years). RESULTS: In the study group the proportion of men was 91.3% and women 8.7%. Histopathological verification confirmed squamous cell carcinomas in 99%. The primary tumour was most often located in the supraglottic area of the larynx (48.0%) and its clinical stage was T3 (33.5%). T1 tumours were statistically significantly more frequently found in the glottis and T4 tumours - in the hypopharynx and in the transglottic area. Swollen lymph nodes in the neck were found in 52.4% of the patients, most often N2 (37.4%). The highest percentage of patients with lymph node reaction was found in the youngest group (76.6%) and the lowest - in the eldest group (30.0%). Swollen lymph nodes were statistically relevantly more frequent in patients with supraglottic or hypopharynx tumour. PMID- 24238108 TI - IL-23 induces IL-22 and IL-17 production in response to Chlamydia muridarum genital tract infection, but the absence of these cytokines does not influence disease pathogenesis. AB - OBJECTIVE: Chlamydia trachomatis infections are a significant cause of reproductive tract pathology. Protective and pathological immune mediators must be differentiated to design a safe and effective vaccine. METHODS: Wild-type mice and mice deficient in IL-22 and IL-23 were infected intravaginally with Chlamydia muridarum, and their course of infection and oviduct pathology were compared. Local genital tract and draining lymph node immune responses were also examined in IL-23-deficient mice. RESULTS: IL-22- and IL-23-deficient mice exhibited normal susceptibility to infection and oviduct pathology. IL-23 was required for the development of a Chlamydia-specific Th17 response in the lymph nodes and for production of IL-22 and IL-17 in the genital tract. However, influx of Th1 and innate immune cells was not compromised in the absence of IL-23. CONCLUSION: IL 22 and IL-23 play either redundant or minimal roles in the pathogenesis of Chlamydia infection in the mouse model. Induction of Th17-associated cytokines by a Chlamydia vaccine should be avoided as these responses are not central to resolution of infection and have pathologic potential. PMID- 24238110 TI - [The treatment of malignant neoplasms of the external ear canal and temporal bone in the Department of Otolaryngology and Oncological Laryngology in Bydgoszcz]. AB - INTRODUCTION, MATERIAL AND METHODS, AIM OF THE STUDY: Evaluation of the methods and results of treatment of 19 cases of malignant tumors of the external auditory meatus and/or temporal bone was performed. RESULTS: In 10 cases planoepithelial carcinoma was diagnosed; in 7 cases basocellulare carcinoma; in 1 case rhabdomyosarcoma; and in 1 case malignant peripheral nerve sheath tumor were histopathologically established. In stage T1 were 8 cases, in T2 - 7, in T3 - 1 and in T4 3 patients were stated based upon clinical and radiological (HRCT and MRI) examination. Three patients in T4 stage were qualified to palliative therapy. In 2 cases radical mastoidectomy was performed, 8 patients underwent partial temporal bone resection. In 6 cases removal of cartilaginous and osseous external auditory meatus was done. In 9 cases local recurrence of tumor was observed during 2 years after surgery. The last 7 cases are under oncological observation. CONCLUSIONS: In conclusion we stressed that patients with malignant tumors of this region are treated in late stages of the disease; it is a main cause of poor diagnosis. PMID- 24238111 TI - [Evaluation of results of using new Baha((r)) abutment and new surgical technique without soft tissue reduction]. AB - The aim of this study is the evaluation of results of using new Baha abutment covered by hydroxyapatite (Baha((r)) BA400, Cochlear Ltd.) which enables new surgical technique without soft tissue reduction. MATERIAL AND METHODS: The results of treatment of 9 adult patients were compared with results of 126 patients implanted earlier by standard technique with soft tissue reduction. RESULTS: In analyzed group we find: slight shortening of time of surgery, similar results of implant stability (RFA) before sound processor connection, very good cosmetic results in 6 patients, some soft tissue overhanging in 2 and retraction pocket formation and inflammation (Holgers 2) in 1, no numbness and pain in operated area in all operated. CONCLUSIONS: New Baha abutment covered by hydroxyapatite (Baha((r)) BA400) enables to safely use new surgical technique without soft tissue reduction. In authors' opinion the most important benefit from this technique is limited bleeding during operation, reduction of using of coagulation and less risk of lesion of nerves and numbness or pain after operation. This technique required less time, but the need of measuring of soft tissue and choosing of proper abutment cause longer preoperative time, so the time of all procedure is only slightly shorter. The esthetic results and healing process confirm the advantage of technique without soft tissue reduction over standard technique. However in patients with a thick soft tissue there is a risk of soft tissue overhanging, so in such cases it is better to make a partial soft tissue reduction. PMID- 24238112 TI - [Facial nerve neurinomas]. AB - INTRODUCTION: Evaluation of diagnostic, surgical technique, treatment results facial nerve neurinomas and its comparison with literature was the main purpose of this study. METHOD AND MATERIALS: Seven cases of patients (2005-2011) with facial nerve schwannomas were included to retrospective analysis in the Department of Otolaryngology, Medical University of Warsaw. All patients were assessed with history of the disease, physical examination, hearing tests, computed tomography and/or magnetic resonance imaging, electronystagmography. Cases were observed in the direction of potential complications and recurrences. RESULTS: Neurinoma of the facial nerve occurred in the vertical segment (n=2), facial nerve geniculum (n=1) and the internal auditory canal (n=4). The symptoms observed in patients were analyzed: facial nerve paresis (n=3), hearing loss (n=2), dizziness (n=1). Magnetic resonance imaging and computed tomography allowed to confirm the presence of the tumor and to assess its staging. Schwannoma of the facial nerve has been surgically removed using the middle fossa approach (n=5) and by antromastoidectomy (n=2). Anatomical continuity of the facial nerve was achieved in 3 cases. In the twelve months after surgery, facial nerve paresis was rated at level II-III degrees HB. There was no recurrence of the tumor in radiological observation. CONCLUSION: Facial nerve neurinoma is a rare tumor. Currently surgical techniques allow in most cases, the radical removing of the lesion and reconstruction of the VII nerve function. The rate of recurrence is low. A tumor of the facial nerve should be considered in the differential diagnosis of nerve VII paresis. PMID- 24238113 TI - [Response changes of inner ear observed after middle ear surgery]. AB - BACKGROUND: Relationship beetwen middle ear surgery and function of the inner ear is known. This problem is often discussed in determination of hearing improvement after otosurgery. AIM: Usefulness of the click evoked otoacoustic emissions (CEOAE) in evaluation of the inner ear function and effectiveness of tympanoplasties is discussed. MATERIAL AND METHODS: Prospective analysis of 70 individuals operated on middle ear problems was performed. Patients were divided into four groups of otosurgeries: stapedoplasty, myringoplasty, type II tympanoplasty, type III tympanoplasty. Otoacoustic emissions and pure tones audiometry were performed before middle ear surgery and 3 months after ear operation. RESULTS: In all established groups improvement in ABG (air bone gap) was observed. Improvement of bone conduction thresholds in the ranges of 5dB was observed in individuals with otosclerosis and type I and type III tympanoplasty. Patients with type II tympanoplasty developed no changes of bone conduction threashold after otosurgery. CONCLUSIONS: Behind routine audiometric diagnostics otoacoustic emissions can be useful in postoperative evaluation of effectiveness of middle ear surgery (especially in patients operated on otosclerosis and in individuals with chronic otitis media with intact ossicular chain). PMID- 24238114 TI - [Anterior commissure status in patients with larynx cancer]. AB - AIM OF THE WORK: Assessment of directions and ways of cancer spreading in the anterior commissure of the larynx, depending on the tumor location, age, sex of patients in a clinical trial and in microscopic serial section study. MATERIALS AND METHODS: The study included 50 larynx preparations obtained from open partial and total laryngectomies (F-7; M-43). For the assessment of larynx anterior commissure microscopic status 28 larynx preparations with macroscopic free anterior commissure were used. For study of the directions and ways of tumor spreading in the anterior commissure served 22 larynx with macroscopic infiltration of anterior commissure. Anterior Commissure (AC) and TNM classifications was used to determine the location and tumor stage. Larynx anterior commissure was extracted and divided into 3 subregions: supraglottic, glottic and subglottic. RESULTS: The direction and the way of cancer propagation in larynx anterior commissure structures is dependent on morphological changes that occur with aging. Cancer spreads in the anterior commissure along the fibers anchoring voice muscle within the Broyles ligament and is seen in tumor cells microembolism. CONCLUSIONS: In patients with cancer of the larynx without macroscopically visible neoplastic lesions in the anterior commissure, cannot be excluded its microinfilration. Changed with age anterior commissure' Broyles ligament by the process of neovascularization and ossification is not an effective protection against the spread of cancer. Directions and the ways of cancer spread in the anterior commissure is similar in men and women. AC classification can be important in qualifying patients for organ preservation surgery and should be supplemented by an additional AC4 degree, taking into account subglottic changes in the anterior commissure of the larynx. PMID- 24238115 TI - Aneurysmal bone cyst of maxilla with ectopic molar tooth - a case report. AB - Aneurysmal cysts of bone are rare non-neoplastic, locally aggressive lesion of bone with propensity for rapid growth, affecting mainly the long bones and spine. It rarely occurs in the head and neck region and within the head and neck mandible (especially the molar areas) is common. Aneurysmal cyst of bone involving the maxilla in the first decade of life is even rarer. We report a case of giant aneurysmal bone cyst of maxilla in eight-year-old male with ectopic molar tooth within the cyst. Is endoscopic excision possible? Endoscopic excision of the cyst was done successfully and no recurrence was noted even after 1 year of follow up. PMID- 24238116 TI - [Laryngeal actinomycosis - a case report and the review of the literature]. AB - We report a case of a 20-year-old man who presented with discreet dysphagia for several months. Indirect laryngoscopy showed a swollen, reddened, thickened epiglottis and smooth, thickened, injected mucosa of aryepiglottic folds and postcricoid region. Thorough work-up was undertaken to exclude specific and non specific infectious diseases, neoplasm, vascular disorders, immunodeficiency syndrome. Histology revealed actinomycotic colonies in biopsy specimen taken from the epiglottis. The inflammation was resolving gradually during long-term antibiotic-therapy. Actinomycosis should be considered in the differential diagnosis in unclear long-lasting inflammation of the supraglottis. The course of untreated actinomycosis can be fatal which is connected with progressive dissemination of the process and secondary abscesses formation in the lungs, liver and brain. PMID- 24238117 TI - Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees. AB - BACKGROUND: The efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine. METHODS: Sixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN gamma-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry. RESULTS: At baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-gamma-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination. CONCLUSION: Our results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a significant increase in CD8+ T cell proliferation. PMID- 24238119 TI - Parastomal hernia is an independent risk factor for incisional hernia in patients with end colostomy. AB - BACKGROUND: Incisional hernia (IH) is the most frequent complication after abdominal operation, with an incidence of 11-20% and up to 35% in risk groups. Known risk groups for IH are abdominal aortic aneurysm and obesity. Our hypothesis is that parastomal hernia (PH) might also represent a risk factor for developing IH. Identifying risk factors can help determine the need for preventive measures such as primary mesh augmentation. METHODS: In a multicenter cross-sectional study, all patients who were operated between 2002 and 2010 by means of a Hartmann procedure or abdominoperineal resection were invited for a follow-up visit to our outpatient clinic. Primary outcome measures were the prevalence of IH and PH. All possible risk factors for IH were scored. A physical examination was performed and, when available, computed tomography was scored for IH and PH. RESULTS: A total of 150 patients were seen in the outpatient clinic. The median follow-up was 49 months (range, 30-75). IH had a prevalence of 37.1%, and PH had a prevalence of 52.3% during physical examination. On CT the prevalence was even greater, ie, 48.3% and 52.9%. IH and PH were both present in the same patient in 30% of all examined and in 35.6% after CT examination. PH was found to be a risk factor for IH on univariate and multivariate logistic regression analyses of variance, with an odds ratio of 7.2 (95% confidence interval 3.3-15.7). In addition, an emergency operation was found to be a risk factor for IH with an odds ratio of 5.8 in the multivariate analyses. CONCLUSION: Patients with a PH have a 7 times greater chance of developing an IH compared to patients without PH. PMID- 24238118 TI - Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial. AB - BACKGROUND: To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes. METHODS: GPs were cluster randomised to one of three intervention groups or a control group. The intervention groups received web-based training in either use of the C reactive protein (CRP) test, communication skills and use of a patient booklet, or training in both. GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Questionnaire. Effects of the interventions on patients were assessed by a post intervention questionnaire assessing patient enablement, satisfaction with the consultation, and beliefs about the risks and need for antibiotics. RESULTS: GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training, and felt that taking part had helped them to reduce prescribing. All GPs perceived reducing prescribing as more important and less risky following the intervention, and GPs in the communication groups reported increased confidence to reduce prescribing. Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful. CONCLUSIONS: Our findings suggest that the interventions should be broadly acceptable to both GPs and patients, as well as feasible to roll out more widely across Europe. There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term, such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them. Given the positive effects of the booklet on patient beliefs and attitudes, it seems logical to extend the use of the patient booklet to all patients. PMID- 24238120 TI - The influence of a contemporaneous portal and hepatic artery revascularization protocol on biliary complications after liver transplantation. AB - BACKGROUND: We sought to compare the impact of sequential and contemporaneous revascularizations of portal vein and hepatic artery on biliary complications in patients undergoing liver transplantation. METHODS: We reviewed 184 patients who underwent liver transplantation in our center, and categorized them into different groups based on the duration of time between the portal venous and hepatic arterial reperfusion: >10 minutes in the sequential portal and hepatic artery revascularization group (SPA; n = 56), and within 1 minute in the contemporaneous portal and hepatic artery revascularization group (CPA; n = 121).The other patients with an interval from 1-10 minutes (n = 7) were excluded. This study then compared the outcomes between the SPA and CPA groups. RESULTS: Cold ischemic time (mean +/- standard deviation) for the SPA and CPA groups were 561 +/- 150 vs 577 +/- 187 minutes, respectively (P = .53). The incidence of biliary complications for the SPA and CPA groups were 14/56 and 11/121, respectively (25% vs 9%; P = .005). By the Clavien-Dindo Classification of Surgical Complications, the biliary complications in SPA group tended to be more severe compared with the CPA group (grade I, 0% vs 0%; II, 14% vs 36%; IIIa, 71% vs 64%; IIIb, 7% vs 0%; IV, 7% vs 0%; P = .10). Among biliary complications, the incidence of nonanatomic strictures was greater in the SPA group (9% vs 2%; P = .03), whereas the difference was not significant for anastomotic strictures (P = .054). Except for a lower serum albumin level in the SPA group 1 day after liver transplantation (P < .001), there are no differences in post-transplant liver function or renal function at 1, 7, and 30 days after transplantation. CONCLUSION: The CPA protocol can decrease the incidence of biliary complications substantially after liver transplantation and should replace the SPA protocol used by some centers in liver transplantation. PMID- 24238121 TI - Pre-existing hypercoagulability in patients undergoing potentially curative cancer resection. AB - BACKGROUND: Rotational thromboelastometry (ROTEM) is a new point-of-care test that allows a rapid and comprehensive evaluation of coagulation. We were among the first to show that ROTEM identifies baseline hypercoagulability in 40% of patients with intra-abdominal malignancies and that hypercoagulability persists for >=1 month after resection. The purpose of this follow-up study was to confirm and extend these observations to a larger population in outpatient preoperative clinics. The hypothesis is that pre-existing hypercoagulability is present in patients undergoing surgery for malignant disease and that coagulation status varies by tumor type. METHODS: After informed consent, preoperative blood samples were drawn from patients undergoing exploratory laparotomies for intra-abdominal malignancies and analyzed with ROTEM. RESULTS: Eighty-two patients were enrolled, including 72 with a confirmed pathologic diagnosis and 10 age-matched controls with benign disease. The most common cancers involved the pancreas (n = 23; 32%), esophagus (n = 19; 26%), liver (n = 12; 17%), stomach (n = 7; 10%), and bile ducts (n = 5; 7%). Preoperative hypercoagulability was detected in 31% (n = 22); these patients were more likely to have lymphovascular invasion (88% vs 50%; P = .011), perineural invasion (77% vs 36%; P = .007), and stage III/IV disease (80% vs 62%; P = .039). More patients with pancreatic tumors (9/23, 39%) were hypercoagulable than with esophageal (3/19, 16%) or liver (2/13, 15%, P = .034) tumors. When only resectable malignancies were considered, clot formation was more rapid (low clot formation time, high alpha) with enhanced maximum clot strength (high maximum clot firmness) in pancreatic versus esophageal or liver cancers and in all cancers versus those with benign disease. CONCLUSION: Preoperative hypercoagulability can be identified with ROTEM and is associated with lymphovascular/perineural invasion and advanced-staged disease in cancer. Compared with other tumor types, pancreatic adenocarcinomas have the greatest risk for hypercoagulability. PMID- 24238122 TI - Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: a proposal of new nodal classification. AB - BACKGROUND: Although the number of metastatic lymph nodes in most gastrointestinal carcinomas is correlated inversely with prognosis, the prognostic value of the number of metastatic lymph nodes in ampullary adenocarcinoma has not been well characterized. METHODS: Lymph node metastasis was assessed in the Surveillance, Epidemiology and End Results database in 1,057 ampullary adenocarcinomas that were operatively resected and for which at least 12 lymph nodes were examined. A complex pattern of survival versus extent of lymph node metastasis was captured by censored local regression. The impact of the extent of lymph nodes metastasis on survival was investigated by use of the K adaptive partitioning algorithm to identify the most significant cut-off points of metastatic lymph nodes affecting survival. RESULTS: Two significant cut-off points (0 and 2) for the metastatic lymph node segregated patients into 3 groups with clinically important differences in median survival: patients with no metastatic lymph node (477 cases) had a median survival of 91 months, patients with 1-2 metastatic lymph nodes (279 cases) had a median survival of 29 months, whereas patients with >=3 metastatic Lymph nodes (301 cases) had a median survival of 19 months (P < .0001). These results were validated with additional single institution dataset (318 cases, P < .0001). CONCLUSION: The present results suggest that the nodal classification of ampullary adenocarcinoma should be categorized N0 (no metastatic lymph node), N1 (1-2 metastatic lymph nodes), and N2 (>=3 metastatic lymph nodes). PMID- 24238123 TI - Sporadic nonfunctioning pancreatic neuroendocrine tumors: prognostic significance of incidental diagnosis. AB - BACKGROUND: Sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed as incidentalomas, and their resection is usually recommended. The prognostic significance of this diagnosis feature is poorly studied, and management of these tumors remains controversial. Clinical, pathologic characteristics and outcome of resected incidentally diagnosed NF-PNET (Inc) were compared with resected symptomatic NF-PNET (Symp) to better assess their biologic behavior and tailor their management. METHODS: From 1994 to 2010, 108 patients underwent resection for sporadic nonmetastatic NF-PNET. Diagnosis was considered as incidental in patients with no abdominal symptoms or symptoms unlikely to be related to tumor mass. Patients with Inc were compared with patients with Symp, regarding demographics, postoperative course, pathology, and disease-free survival (DFS). RESULTS: Of the 108 patients, 65 (61%) had incidentally diagnosed tumors. Pancreas-sparing pancreatectomies (enucleation/central pancreatectomy) were performed more frequently in Inc (62% vs 30%, P = .001). Inc tumors were more frequently <20 mm (65% vs 42%, P = .019), staged T1 (62% vs 33%, P = .0001), node negative (85% vs 60%; P = .005), and grade 1 (66% vs 33%, P = .0001). One postoperative death occurred in the Inc group, and postoperative morbidity was similar between the two groups (60% vs 65%, P = .59). DFS was substantially better in the Inc group (5-year DFS = 92% vs 82%, P = .0016). CONCLUSION: Incidentally diagnosed NF-PNETs are associated with less aggressive features compared with symptomatic lesions but cannot always be considered to be benign. Operative resection remains recommended for most. Incidentally diagnosed NF-PNET may be good candidates for pancreas-sparing pancreatectomies. PMID- 24238124 TI - Repeat pancreatectomy for pancreatic ductal cancer recurrence in the remnant pancreas after initial pancreatectomy: is it worthwhile? AB - BACKGROUND: The clinical implications of repeat completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas after initial pancreatectomy have not been clarified. We retrospectively analyzed our patients and evaluated the clinical implications of repeat pancreatectomy for isolated local recurrence in the remnant pancreas after initial resection for pancreatic cancer. METHODS: One-hundred seventy patients who had recurrence of pancreatic cancer out of 326 patients who had initially undergone resection for pancreatic cancer were included in this study. Sixty-seven of 170 recurrent patients were diagnosed as having isolated local recurrence of pancreatic cancer. Eleven of these 67 patients with isolated local recurrence only in the remnant pancreas underwent repeat pancreatectomy. Characteristics and operative outcomes for these 11 patients with repeat pancreatectomy were analyzed and evaluated in comparison with other recurrent patients. RESULTS: Among 170 patients with recurrence after initial resection for pancreatic cancer, the median survival time was 78.2 and 20.3 months after initial resection, in the repeat pancreatectomy group and the unresectable group, respectively (P < .001), and the 2- and 5-year survival probability rates after initial resection were 91%, and 82% vs 42%, and 13%, respectively. Among 67 patients with isolated local recurrence, the median survival time after repeat resection or diagnosis of recurrence was 25.0 and 9.3 months, and the 2- and 5-year survival probability rates after repeat resection or diagnosis of recurrence were and 61% and 46% vs 19% and 6.2% in the repeat pancreatectomy group and the unresectable group, respectively (P < .01). There was no difference in survivals between the unresectable isolated local recurrence group and the unresectable nonlocal recurrence group. CONCLUSION: Repeat pancreatectomy might bring about beneficial effects on prognosis in selected patients with isolated local recurrence in the remnant pancreas after initial pancreatectomy for pancreatic cancer without increased operative morbidity or mortality. PMID- 24238125 TI - Cytoskeleton-associated protein 2 is a potential predictive marker for risk of early and extensive recurrence of hepatocellular carcinoma after operative resection. AB - BACKGROUND: De principe transplantation is an attractive strategy for the treatment of patients with hepatocellular carcinoma (HCC). The most important issue for this strategy is how to predict the risk of early and extensive recurrence. The present study aimed to identify a molecule associated with early and extensive recurrence of HCC after resection. METHODS: Differentially expressed genes were screened by DNA microarray analysis with the use of 12 HCC samples from patients who had different clinical courses based on the timing and extent of recurrence after operative resection. Furthermore, the obtained results were validated in 60 independent samples by quantitative real-time reverse transcription-polymerase chain reaction. Immunohistochemistry was performed to assess gene expression at the protein level. RESULTS: Microarray analysis and quantitative reverse transcription-polymerase chain reaction revealed cytoskeleton-associated protein 2 (CKAP2) as a candidate gene associated with early and extensive recurrence of HCC after resection. This observation was confirmed through examination of independent set samples, in which patients with greater-level CKAP2 mRNA expression exhibited shorter recurrence-free survival. Immunohistochemistry showed CKAP2 protein expression was associated with early (<=3 years) and extensive recurrence (beyond Milan criteria) after operative resection. CONCLUSION: Immunohistochemical CKAP2 expression might be a potential biologic marker for identifying HCC patients at risk of early and extensive recurrence after operative resection. PMID- 24238126 TI - Laparoscopic versus open gastrectomy for gastric cancer: long-term oncologic results. AB - BACKGROUND: Data are lacking regarding the oncologic safety of laparoscopic gastrectomy (LG) for the treatment of gastric cancer. The aim of this study was to compare the long-term outcomes of LG with open gastrectomy (OG) for the treatment of gastric cancer. METHODS: A total of 1,874 patients underwent curative distal or total gastrectomy for gastric adenocarcinoma between May 2003 and December 2009 and were included in this retrospective study. Recurrence-free survival and recurrence pattern were compared according to each tumor stage, and a subgroup analysis was performed in advanced gastric cancer patients who underwent D2 lymphadenectomy. RESULTS: Of 1,874 patients, 816 were treated with OG and 1,058 with LG. No differences were observed in recurrence-free survival rates between the LG and the OG groups for any tumor stage. The number of harvested lymph nodes was similar between the two groups when analyzed according to tumor progression, operative procedure, and extent of lymphadenectomy. There were no differences between the 2 groups when we compared recurrence patterns after stratifying for tumor stage. The subgroup analysis in advanced gastric cancer patients who underwent D2 lymphadenectomy showed that there was no difference in the recurrence-free survival rates for any tumor stage between the 2 groups. Multivariate analysis indicated that the type of operative approach did not influence recurrence in either early or advanced gastric cancer patients. CONCLUSION: LG for gastric cancer is an oncologically safe procedure with comparable long-term outcomes with OG. PMID- 24238127 TI - Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of L-NAME in rats: role of GLP-1 and GLP-1 receptor. AB - The present study was undertaken to assess the possible protective effects of sitagliptin, a dipeptidyl peptidase 4-inhibitor (DPP4), against Nomega-nitro-L arginine methyl ester (L-NAME) induced hypertensive nephropathy in rats. Hypertension was induced in adult rats by administration of L-NAME for 6 weeks. Rats were treated with sitagliptin (10mg/kg/day or 30 mg/kg/day) for six weeks. Chronic L-NAME administration resulted in depletion of serum nitric oxide (NO) associated with elevation in the mean arterial pressure. When compared with the control group; serum urea, serum creatinine, albuminuria, urinary N-acetyl-beta-d glucosaminidase (NAG) level and renal tissue malondialdhyde (MDA) content were significantly elevated, while creatinine clearance, serum level of glucagon like peptide-1 (GLP-1) as well as renal tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were signifcantly decreased in L-NAME treated group. Renal expression of mRNA for eNOS and GLP-1 receptors were reduced in the L-NAME treated group as compared with the control group. Treatment with sitagliptin (10mg/kg or 30 mg/kg) successfully ameliorated the deleterious effects of L-NAME on the all tested parameters. Our study indicates a novel protective effect of sitagliptin against L-NAME induced hypertensive nephropathy. An effect which is mediated through, increasing serum level of GLP-1, upregulation of GLP-1 receptors, which in turn, lead to induction of expression eNOS, increased serum NO level, tandem with decreased lipid perodixation and restore the antioxidant defense mechanisms. It is worth mentioning that the effects produced by sitaglipin (30 mg/kg) were superior to the effects obtained by the lower dose. PMID- 24238128 TI - MR imaging techniques of the bowel. AB - Due to advances in technology, magnetic resonance is an increasingly popular method for evaluating the small bowel and colon because of the lack of radiation, wealth of information provided by the images, and growing demand from gastroenterologists, surgeons, and oncologists. Careful attention to proper technique, however, is necessary to obtain high-quality images. Factors that need to be considered for successful magnetic resonance of the bowel include method for administration of oral or rectal contrast, patient positioning, need for antiperistaltic medication, and imaging sequences and planes. PMID- 24238129 TI - MR imaging of the small bowel in Crohn disease. AB - MR enterography has an established role in evaluating patients with Crohn disease providing essential complementary information to clinical assessment, and as an indispensible adjunct to clinical tools such as colonoscopy. MR enterography examinations can establish the diagnosis of Crohn disease, evaluate disease activity and complications, and assess treatment response, thus providing support for clinical decision-making. Currently, MR imaging findings are highly predictive of tissue inflammation and can be used clinically to guide clinical care. PMID- 24238130 TI - MR colonography in inflammatory bowel disease. AB - MR colonography has a high diagnostic accuracy for detecting Crohn disease (CD) activity and determining the extent and severity of lesions. In the setting of stricturing CD, MR colonography can provide a detailed map of the lesions, which is useful for clinical decision making. MR colonography can be used as an alternative to conventional colonoscopy in the setting of CD, or as a complementary tool in selected patients with ulcerative colitis. This article reviews the spectrum of MR colonography findings in colonic inflammatory bowel disease and discusses the potential applications and limitations of MR colonography. PMID- 24238131 TI - New magnetic resonance imaging modalities for Crohn disease. AB - Magnetic resonance (MR) enterography has an increasing role in the evaluation of the small bowel in patients with Crohn disease. MR enterography is accurate for disease assessment and can influence the choice of therapy. Functional sequences may increase the role of MR enterography in Crohn disease. Techniques such as high-resolution MR enterography, diffusion-weighted imaging, dynamic contrast enhanced MR imaging, magnetization transfer, and MR motility imaging may allow better assessment of disease extent, activity, and severity. Quantitative analysis using these advanced techniques as well as the standard techniques may provide methods for evaluating and following the disease in the future. PMID- 24238132 TI - Noninflammatory conditions of the small bowel. AB - Magnetic resonance (MR) imaging has been playing an evolving role in evaluating noninflammatory small-bowel conditions, such as tumors and malabsorption syndrome. MR imaging has shown to be superior to other diagnostic methods in identifying tumors of the small bowel. MR enterography and MR enteroclysis are both valid for studying noninflammatory conditions of the small intestine, although MR enteroclysis may be considered the modality of choice because of its accuracy in the diagnosis of small-bowel neoplasms. Intraluminal and extraluminal MR findings, combined with contrast-agent enhancement and functional information, help to make an accurate diagnosis and consequently to characterize small-bowel diseases. PMID- 24238133 TI - Magnetic resonance colonography for screening and diagnosis of colorectal cancer. AB - Colorectal cancer is the second most common cause of cancer-related death in Europe and the United States, and a major cause of mortality. Early detection of colorectal cancer and its precursors reduces mortality and morbidity, and a minimally invasive screening tool is essential for high patient acceptance and participation. To achieve this goal, computed tomographic colonography and magnetic resonance (MR) colonography have been introduced. A wide variety of methods of bowel preparation, colon distension, and imaging exists for MR colonography. This article presents an up-to-date overview of the status of MR colonography in screening for colorectal cancer, and its diagnosis. PMID- 24238134 TI - Magnetic resonance imaging of rectal and anal cancer. AB - Magnetic resonance imaging plays a pivotal role in the imaging and staging of rectal and anal carcinomas. Rectal adenocarcinomas and anal squamous cell carcinomas behave differently, and are staged and treated differently. This article attempts to explain these 2 entities, which share the same regions of interest, in a comprehensive manner. PMID- 24238135 TI - Magnetic resonance imaging of perianal fistulas. AB - Perianal fistulization is the result of a chronic inflammation of the perianal tissues. A wide spectrum of clinical manifestations, ranging from simple to complex fistulas, can be seen, the latter especially in patients with Crohn disease. Failure to detect secondary tracks and hidden abscesses may lead to therapeutic failure, such as insufficient response to medical treatment and relapse after surgery. Currently, magnetic resonance (MR) imaging is the preferred technique for evaluating perianal fistulas and associated complications. Initially used most often in the preoperative setting, MR imaging now also plays an important role in evaluating the response to medical therapy. PMID- 24238137 TI - Bowel imaging. PMID- 24238138 TI - Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma Study Group. AB - BACKGROUND: The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract. PATIENTS AND METHODS: Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. RESULTS: The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 - 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. CONCLUSION: Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity. PMID- 24238139 TI - Bacterial communities and syntrophic associations involved in anaerobic oxidation of methane process of the Sonora Margin cold seeps, Guaymas Basin. AB - SUMMARY: The Sonora Margin cold seeps present on the seafloor a patchiness pattern of white microbial mats surrounded by polychaete and gastropod beds. These surface assemblages are fuelled by abundant organic inputs sedimenting from the water column and upward-flowing seep fluids. Elevated microbial density was observed in the underlying sediments. A previous study on the same samples identified anaerobic oxidation of methane (AOM) as the potential dominant archaeal process in these Sonora Margin sediments, probably catalysed by three clades of archaeal anaerobic methanotrophs (ANME-1, ANME-2 and ANME-3) associated with bacterial syntrophs. In this study, molecular surveys and microscopic observations investigating the diversity of Bacteria involved in AOM process, as well as the environmental parameters affecting the composition and the morphologies of AOM consortia in the Sonora Margin sediments were carried out. Two groups of Bacteria were identified within the AOM consortia, the Desulfosarcina/Desulfococcus SEEP SRB-1a group and a Desulfobulbus-related group. These bacteria showed different niche distributions, association specificities and consortia architectures, depending on sediment surface communities, geochemical parameters and ANME-associated phylogeny. Therefore, the syntrophic AOM process appears to depend on sulphate-reducing bacteria with different ecological niches and/or metabolisms, in a biofilm-like organic matrix. PMID- 24238141 TI - Be a professional philanthropist. PMID- 24238142 TI - It takes a village to communicate the Dietary Guidelines for Americans and MyPlate. PMID- 24238140 TI - Asymmetric segregation of template DNA strands in basal-like human breast cancer cell lines. AB - BACKGROUND AND METHODS: Stem or progenitor cells from healthy tissues have the capacity to co-segregate their template DNA strands during mitosis. Here, we set out to test whether breast cancer cell lines also possess the ability to asymmetrically segregate their template DNA strands via non-random chromosome co segregation, and whether this ability correlates with certain properties attributed to breast cancer stem cells (CSCs). We quantified the frequency of asymmetric segregation of template DNA strands in 12 human breast cancer cell lines, and correlated the frequency to molecular subtype, CD44+/CD24-/lo phenotype, and invasion/migration ability. We tested if co-culture with human mesenchymal stem cells, which are known to increase self-renewal, can alter the frequency of asymmetric segregation of template DNA in breast cancer. RESULTS: We found a positive correlation between asymmetric segregation of template DNA and the breast cancer basal-like and claudin-low subtypes. There was an inverse correlation between asymmetric segregation of template DNA and Her2 expression. Breast cancer samples with evidence of asymmetric segregation of template DNA had significantly increased invasion and borderline significantly increased migration abilities. Samples with high CD44+/CD24-/lo surface expression were more likely to harbor a consistent population of cells that asymmetrically segregated its template DNA; however, symmetric self-renewal was enriched in the CD44+/CD24-/lo population. Co-culturing breast cancer cells with human mesenchymal stem cells expanded the breast CSC pool and decreased the frequency of asymmetric segregation of template DNA. CONCLUSIONS: Breast cancer cells within the basal like subtype can asymmetrically segregate their template DNA strands through non random chromosome segregation. The frequency of asymmetric segregation of template DNA can be modulated by external factors that influence expansion or self-renewal of CSC populations. Future studies to uncover the underlying mechanisms driving asymmetric segregation of template DNA and dictating cell fate at the time of cell division may explain how CSCs are maintained in tumors. PMID- 24238143 TI - Setting strategic direction for complex publicly funded foodservice systems: application of multicriteria decision analysis. PMID- 24238144 TI - Perspectives about family meals from single-headed and dual-headed households: a qualitative analysis. AB - Cross-sectional and longitudinal research has shown that family meals are protective for adolescent healthful eating behaviors. However, little is known about what parents think of these findings and whether parents from single- vs dual-headed households have differing perspectives about the findings. In addition, parents' perspectives regarding barriers to applying the findings on family meals in their own homes and suggestions for more widespread adoption of the findings are unknown. The current study aimed to identify single- and dual headed household parents' perspectives regarding the research findings on family meals, barriers to applying the findings in their own homes, and suggestions for helping families have more family meals. The current qualitative study included 59 parents who participated in substudy of two linked multilevel studies-EAT 2010 (Eating and Activity in Teens) and Families and Eating and Activity in Teens (F EAT). Parents (91.5% female) were racially/ethnically and socioeconomically diverse. Data were analyzed using a grounded theory approach. Results from the current study suggest that parents from both single- and dual-headed households have similar perspectives regarding why family meals are protective for healthful eating habits for adolescents (eg, provides structure/routine, opportunities for communication, connection), but provide similar and different reasons for barriers to family meals (eg, single-headed=cost vs dual-headed=lack of creativity) and ideas and suggestions for how to increase the frequency of family meals (eg, single-headed=give fewer options vs dual-headed=include children in the meal preparation). Findings can help inform public health intervention researchers and providers who work with adolescents and their families to understand how to approach discussions regarding reasons for having family meals, barriers to carrying out family meals, and ways to increase family meals depending on family structure. PMID- 24238145 TI - Council on Future Practice Visioning Report and consensus agreement for moving forward the continuum of dietetics education, credentialing, and practice. PMID- 24238146 TI - Avoiding ethical and legal issues in practice settings. PMID- 24238147 TI - What are the current guidelines for pediatric non-alcoholic fatty liver disease? PMID- 24238148 TI - Time-to-diagnosis and symptoms of myeloma, lymphomas and leukaemias: a report from the Haematological Malignancy Research Network. AB - BACKGROUND: Prior to diagnosis, patients with haematological cancers often have multiple primary care consultations, resulting in diagnostic delay. They are less likely to be referred urgently to hospital and often present as emergencies. We examined patient perspectives of time to help-seeking and diagnosis, as well as associated symptoms and experiences. METHODS: The UK's Haematological Malignancy Research Network (http://www.hmrn.org) routinely collects data on all patients newly diagnosed with myeloma, lymphoma and leukaemia (>2000 annually; population 3.6 million). With clinical agreement, patients are also invited to participate in an on-going survey about the circumstances leading to their diagnosis (presence/absence of symptoms; type of symptom(s) and date(s) of onset; date medical advice first sought (help-seeking); summary of important experiences in the time before diagnosis). From 2004-2011, 8858 patients were approached and 5038 agreed they could be contacted for research purposes; 3329 requested and returned a completed questionnaire. The duration of the total interval (symptom onset to diagnosis), patient interval (symptom onset to help-seeking) and diagnostic interval (help-seeking to diagnosis) was examined by patient characteristics and diagnosis. Type and frequency of symptoms were examined collectively, by diagnosis and compared to UK Referral Guidelines. RESULTS: Around one-third of patients were asymptomatic at diagnosis. In those with symptoms, the median patient interval tended to be shorter than the diagnostic interval across most diseases. Intervals varied markedly by diagnosis: acute myeloid leukaemia being 41 days (Interquartile range (IQR) 17-85), diffuse large B-cell lymphoma 98 days (IQR 53-192) and myeloma 163 days (IQR 84-306). Many symptoms corresponded to those cited in UK Referral Guidelines, but some were rarely reported (e.g. pain on drinking alcohol). By contrast others, absent from the guidance, were more frequent (e.g. stomach and bowel problems). Symptoms such as tiredness and pain were common across all diseases, although some specificity was evident by sub-type, such as lymphadenopathy in lymphoma and bleeding and bruising in acute leukaemia. CONCLUSIONS: Pathways to diagnosis are varied and can be unacceptably prolonged, particularly for myeloma and some lymphomas. More evidence is needed, along with interventions to reduce time-to-diagnosis, such as public education campaigns and GP decision-making aids, as well as refinement of existing Referral Guidelines. PMID- 24238149 TI - Acute dyskinesia, myoclonus, and akathisa in an adolescent male abusing quetiapine via nasal insufflation: a case study. AB - BACKGROUND: Although the benefits of antipsychotic pharmacotherapy can be pronounced, many patients develop unwanted adverse effects including a variety of movement disorders. Compared with the traditional antipsychotics, the atypical antipsychotics have a decreased risk for associated movement disorders. Drug induced movement disorders can occur, however, and the risk of adverse events can increase significantly when medications are abused. CASE PRESENTATION: We describe the case of a 13-year-old male who presented to an emergency department with acute movement disorders after nasal insufflation of crushed quetiapine. The patient was admitted and successfully treated for neuroleptic toxicity with intravenous antihistamine pharmacotherapy. His primary care provider and psychiatrist were notified of the abuse, quetiapine was discontinued, and the patient was discharged and referred to a drug and alcohol awareness and abuse program. CONCLUSIONS: The abuse of quetiapine has unfortunately become more common. This unique case report of acute movement disorders following nasal insufflation of quetiapine highlights the need for heightened vigilance when prescribing quetiapine and for increased awareness and education regarding medication-abuse. PMID- 24238151 TI - Pre-eclampsia affects cord blood NK cell expression of activation receptors and serum cytokine levels but not CB monocyte characteristics. AB - PROBLEM: Maternal immunopathology in pre-eclampsia is well studied; however, less is known regarding the immunological effects on the newborns. Increased inflammation and activation of immune cells at the fetal-maternal interface in pre-eclampsia could influence the neonatal immune compartment. METHOD OF STUDY: Monocytes and natural killer (NK) cells from cord blood (CB) of children with pre eclamptic or healthy mothers were analyzed by flow cytometry for surface markers and intracellular cytokines. In addition, serum cytokine profiles were investigated using ELISA or cytometric bead array. RESULTS: Neonates born to pre eclamptic mothers had an inflammatory serum cytokine profile. While CB monocyte characteristics seemed unaffected, CB NK cells from pre-eclamptic pregnancies had higher NKp30, but borderline lower NKG2D expression. CONCLUSION: In utero inflammatory priming of neonatal innate immunity taking place in pre-eclamptic pregnancies might influence specific NK cell functions in newborns. PMID- 24238150 TI - Predicting tissue specific transcription factor binding sites. AB - BACKGROUND: Studies of gene regulation often utilize genome-wide predictions of transcription factor (TF) binding sites. Most existing prediction methods are based on sequence information alone, ignoring biological contexts such as developmental stages and tissue types. Experimental methods to study in vivo binding, including ChIP-chip and ChIP-seq, can only study one transcription factor in a single cell type and under a specific condition in each experiment, and therefore cannot scale to determine the full set of regulatory interactions in mammalian transcriptional regulatory networks. RESULTS: We developed a new computational approach, PIPES, for predicting tissue-specific TF binding. PIPES integrates in vitro protein binding microarrays (PBMs), sequence conservation and tissue-specific epigenetic (DNase I hypersensitivity) information. We demonstrate that PIPES improves over existing methods on distinguishing between in vivo bound and unbound sequences using ChIP-seq data for 11 mouse TFs. In addition, our predictions are in good agreement with current knowledge of tissue-specific TF regulation. CONCLUSIONS: We provide a systematic map of computationally predicted tissue-specific binding targets for 284 mouse TFs across 55 tissue/cell types. Such comprehensive resource is useful for researchers studying gene regulation. PMID- 24238152 TI - Sodium thiosulfate for the treatment of calcinosis secondary to juvenile dermatomyositis. AB - We report the successful use of sodium thiosulfate in a patient with juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This therapy may have a role in improving calcinosis, even if more studies are necessary to determine the safety and efficacy of this treatment in juvenile dermatomyositis-related calcinosis. PMID- 24238153 TI - Pediatric brainstem gangliogliomas show BRAF(V600E) mutation in a high percentage of cases. AB - Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic-and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAF(V600E) mutation, with two others exhibiting an equivocal result by this method. BRAF(V600E) was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAF(V600E) showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAF(V600E) using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem GGs. BRAF(V600E) -targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies. PMID- 24238155 TI - American Academy of Dermatology Choosing Wisely List: helping dermatologists and their patients make smart decisions about their care and treatment. PMID- 24238154 TI - Subconjunctival hibernoma in a dog. AB - A 10-year-old, castrated male, German Shepherd mixed-breed dog was presented to Kansas State University Veterinary Health Center for evaluation of a subconjunctival swelling in the ventral fornix of the left orbit. The owner elected to pursue excision of the mass 2 years after initial consultation following a sudden change in the size and color of the lesion. An excisional biopsy was performed, and the mass along with its associated capsule were submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for histopathologic evaluation, which confirmed the diagnosis of a hibernoma. Fourteen months following excision, the patient showed no evidence of tumor regrowth. PMID- 24238156 TI - Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. AB - BACKGROUND: The possible connection between psoriasis with cardiovascular disease and associated risk factors has been implied, but inconsistent results have been reported. OBJECTIVE: We sought to create an overview and statistical summary of the previous literature with elucidating subgroup analysis. METHODS: This was a meta-analysis of observational studies using random effect statistics. A systematic search of observational studies of psoriasis as study variable and cardiovascular disease and associated risk factors as outcome, published before October 25, 2012, was conducted. RESULTS: Of 835 references in the original search, 75 relevant articles were identified. We included 503,686 cases and 29,686,694 controls. Psoriasis was associated with cardiovascular disease in total (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.2-1.7), ischemic heart disease (OR 1.5; 95% CI 1.2-1.9), peripheral vascular disease (OR 1.5; 95% CI 1.2 1.8), atherosclerosis (OR 1.1; 95% CI 1.1-1.2), diabetes (OR 1.9; 95% CI 1.5 2.5), hypertension (OR 1.8; 95% CI 1.6-2.0), dyslipidemia (OR 1.5; 95% CI 1.4 1.7), obesity by body mass index (OR 1.8; 95% CI 1.4-2.2), obesity by abdominal fat (OR 1.6; 95% CI 1.2-2.3), and the metabolic syndrome (OR 1.8; 95% CI 1.2 2.8), but not associated with cerebrovascular disease (OR 1.1; 95% CI 0.9-1.3) and cardiovascular mortality (OR 0.9; 95% CI 0.4-2.2). The strongest associations were seen in hospital-based studies and psoriatic arthritis. Population-based studies did not show significant associations, with the exception of dyslipidemia. LIMITATIONS: The heterogeneity of the studies makes clinical interpretation challenging. CONCLUSIONS: In aggregate, psoriasis was associated with ischemic heart disease and cardiovascular risk factors. The association was only significant for hospital-based studies, except for dyslipidemia, which was also significant in population-based studies. PMID- 24238157 TI - The modern minor: consent and decision-making in pediatric dermatology. PMID- 24238158 TI - Dermatologists' blind side: the ethical implications of in-house dermatopathology laboratories. PMID- 24238159 TI - Guidelines of care for the management of primary cutaneous melanoma. PMID- 24238160 TI - Mortality after dermatologic surgery for nonmelanoma skin cancer in patients aged 80 years and older. PMID- 24238161 TI - Life expectancy after Mohs micrographic surgery in patients aged 80 years and older. PMID- 24238162 TI - Possible reconsideration of the Nail Psoriasis Severity Index (NAPSI) score. PMID- 24238163 TI - Follicular mucinosis in childhood. PMID- 24238164 TI - Invited reply to "Possible reconsideration of the Nail Psoriasis Severity Index (NAPSI) score". PMID- 24238165 TI - Primum non nocere, or treat the patient, not the disease. PMID- 24238166 TI - Drug reaction with eosinophilia and systemic symptoms syndrome: a picture is worth a thousand words. PMID- 24238167 TI - Drug reaction with eosinophilia and systemic symptoms syndrome and toxic epidermal necrolysis: an uncommon confounding oral mucosal overlap. PMID- 24238168 TI - Dysphagia, a major early manifestation in DRESS syndrome. PMID- 24238169 TI - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and dysphagia: a noteworthy association. PMID- 24238170 TI - The protective effect of sunscreens, vitamin E 6% cream, and betamethasone 0.1% cream on solar-simulating radiation-induced erythema and neutrophil influx. PMID- 24238171 TI - Using a diagnostic score when reporting the long-term sequelae of the drug reaction with eosinophilia and systemic symptoms syndrome. PMID- 24238172 TI - Reply to: "Using a diagnostic score when reporting the long-term sequelae of the drug reaction with eosinophilia and systemic symptoms". PMID- 24238173 TI - Scleromyxedema: a novel therapeutic approach. PMID- 24238174 TI - Liposuction for axillary hyperhidrosis. PMID- 24238175 TI - Emperipolesis is not pathognomonic for Rosai-Dorfman disease: rhinoscleroma mimicking Rosai-Dorfman disease, a clinical series. PMID- 24238176 TI - Dermatology urgent care clinic: a survey of referring physician satisfaction. PMID- 24238177 TI - Acrylic nail curing UV lamps: high-intensity exposure warrants further research of skin cancer risk. PMID- 24238178 TI - Intralesional interferon alfa-2b for refractory, recurrent squamous cell carcinoma of the face. PMID- 24238179 TI - Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents. AB - The acute and chronic consequences of ultraviolet radiation on human skin are reviewed. An awareness of variations in naturally occurring photoprotective agents and the use of glass, sunglasses, and fabric can lead to effective protection from the deleterious effects of ultraviolet radiation. New systemic agents, including Polypodium leucotomos, afamelanotide, and antioxidants have potential as photoprotective agents. PMID- 24238180 TI - Photoprotection: part II. Sunscreen: development, efficacy, and controversies. AB - In addition to the naturally occurring, physical, and systemic photoprotective agents reviewed in part I, topical ultraviolet radiation filters are an important cornerstone of photoprotection. Sunscreen development, efficacy, testing, and controversies are reviewed in part II of this continuing medical education article. PMID- 24238183 TI - Dermoscopy of giant molluscum contagiosum. PMID- 24238184 TI - Chronic pruritic nipple in a 75-year-old woman. PMID- 24238185 TI - At-home chiropody as an alternative/complementary treatment for palmoplantar keratoderma. PMID- 24238186 TI - Allergic contact dermatitis caused by a blood pressure cuff. PMID- 24238187 TI - Fixed drug eruption occurring in vitiliginous skin. PMID- 24238188 TI - Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus successfully treated with a single dose of etanercept: report of three cases. PMID- 24238189 TI - Bowen disease of the vulva successfully treated with intraarterial infusion chemotherapy. PMID- 24238190 TI - Onychomadesis during bullous pemphigoid. PMID- 24238191 TI - Comedonal Darier disease: report of 2 cases. PMID- 24238192 TI - Papular xanthomas with destructive arthritis. PMID- 24238193 TI - ER/PR positive epidermotropic primary cutaneous eccrine carcinoma as a cutaneous manifestation of MEN 2B. PMID- 24238194 TI - Extended eosinophilic pustular folliculitis with reactive bone marrow hypereosinophilia responsive to combined treatment with indomethacin, dapsone, and narrow-band UVB phototherapy. PMID- 24238195 TI - Intralymphatic histiocytosis in association with severe osteoarthritis of the shoulder. PMID- 24238196 TI - Cutaneous plasmablastic lymphoma in a nonimmunocompromised patient. PMID- 24238197 TI - Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives' training in Catalan hospitals accredited as centers for normal birth. AB - BACKGROUND: The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives' level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. METHODS: A descriptive, cross sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. RESULTS: Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. CONCLUSIONS: Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized. PMID- 24238198 TI - Transpositional modification of the posterior auricular pull-through flap: a new twist. PMID- 24238199 TI - Orthokeratology: does it live up to expectations? PMID- 24238200 TI - Myopia control in children through refractive therapy gas permeable contact lenses: is it for real? AB - PURPOSE: To compare the safety and efficacy of orthokeratology as a nonsurgical treatment for myopia in children with alternate methods, such as soft contact lenses, rigid gas permeable lenses, and spectacles, throughout multiple studies. DESIGN: Perspective with literature review. METHODS: Analysis of recent studies to determine the safety and effectiveness of orthokeratology versus soft contact lenses, rigid gas permeable lenses, and spectacles in children. RESULTS: In all of the studies reviewed, the use of orthokeratology lenses proved to reduce myopia, to improve visual acuity, and, with the exception of the SMART study, to reduce the rate of axial elongation. Orthokeratology has been shown to be as effective as other methods in treating myopia and to be more effective at treating axial elongation. There were no major adverse events in any of the studies comparing orthokeratology with other methods of myopia treatment. CONCLUSIONS: Studies show that the use of orthokeratology is a safe and efficacious nonsurgical treatment for myopia and that it is capable of slowing axial elongation, making it an effective myopic treatment for children. PMID- 24238201 TI - Reply: To PMID 23876863. PMID- 24238202 TI - Surgical results of a muscle transposition procedure for abducens palsy without tenotomy and muscle splitting. PMID- 24238203 TI - Reply: To PMID 23677137. PMID- 24238204 TI - Posterior capsule opacification with the iMics1 NY-60 and AcrySof SN60WF 1-piece hydrophobic acrylic intraocular lenses: 3-year results of a randomized trial. PMID- 24238205 TI - Endothelial keratoplasty: prospective, randomized, masked clinical trial comparing an injector with forceps for tissue insertion. PMID- 24238206 TI - Reply: To PMID 23522354. PMID- 24238207 TI - Incidence of pineal gland cyst and pineoblastoma in children with retinoblastoma during the chemoreduction era. PMID- 24238208 TI - Reply: To PMID 23876864. PMID- 24238209 TI - Endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of culture-proven cases. PMID- 24238210 TI - Reply: To PMID 23540710. PMID- 24238211 TI - Antimicrobial activity of untypical lipid compounds in the cuticular and internal lipids of four fly species. AB - AIMS: This article describes the qualitative and quantitative analyses of untypical compounds in the cuticular and internal lipids of four dipteran species. For isolated compounds, antimicrobial activity against 18 reference strains of bacteria and fungi was determined. METHODS AND RESULTS: In this study, gas chromatography (GC) combined with mass spectrometry (GC-MS) was used to analyse the surface and internal compounds of four fly species. Seven untypical compounds from both pre-imaginal and imaginal stages of examined insects were identified. Azelaic acid (AA) was the most abundant, while phenylacetic and phenylpropionic acids occurred in lower concentration. Minor quantities of sebacic acid, 2-methyl-2-hydroxybutanoic acid, tocopherol acetate and trace amounts of 2,4-decadienal were also detected. Tocopherol acetate was found only in cuticular lipids of Musca domestica larvae. Each compound was tested against several species of fungi and bacteria by determining minimal inhibitory concentration (MIC). Human pathogenic fungi were also investigated. Phenylpropionic acid showed the greatest antifungal activity. Bacterial strains were insensitive to the presence of identified compounds, apart from 2,4 decadienal which strongly inhibited bacterial growth. CONCLUSIONS: This is the first time that the chemical composition and the antimicrobial activity of untypical compounds in the cuticular and internal lipids of four fly species has been analysed. SIGNIFICANCE AND IMPACT OF THE STUDY: Determination of untypical compounds and their antimicrobial activity can effectively contribute to the knowledge concerning insect defence mechanisms. PMID- 24238213 TI - Late adverse events after enhanced and unenhanced MRI and CT: a prospective study. AB - Prospective evaluation of frequency of late and very late adverse events in patients undergoing enhanced or unenhanced magnetic resonance imaging (MRI) or computed tomography (CT). The imaging procedure was performed according to the protocols of the department. All patients were contacted 3 days after their imaging procedure for the occurrence of late adverse events (LAEs) and a month later for the occurrence of very late adverse events (VLAEs) using a structured questionnaire. A total of 1042 (71%) among 1473 patients completed both the 3-day and 1-month questionnaire. The incidence of LAEs was significantly higher in the enhanced MRI (38%) and CT (27%) groups than unenhanced MRI (20%) and CT (16%) groups. The frequency of nausea, dizziness, abdominal pain and diarrhoea was significantly higher in the enhanced MRI group than in the MRI control group, while taste sensation was reported more frequent in the enhanced CT group than in the CT control group. The incidence of VLAEs was significantly higher in the enhanced CT (21%) than unenhanced CT group (13%). The same LAEs and VLAEs were reported in all four groups. LAEs and VLAEs were reported more often in patients with allergy in both the enhanced and unenhanced groups. The incidence of LAEs and VLAEs was higher in the enhanced groups than in the unenhanced groups. The most reported adverse events in the enhanced groups were also reported in the unenhanced groups. Patients with allergy reported LAE and VLAE more often. This suggests that adverse events may not always be caused by the contrast media. PMID- 24238212 TI - Mek inhibition results in marked antitumor activity against metastatic melanoma patient-derived melanospheres and in melanosphere-generated xenografts. AB - One of the key oncogenic pathways involved in melanoma aggressiveness, development and progression is the RAS/BRAF/MEK pathway, whose alterations are found in most patients. These molecular anomalies are promising targets for more effective anti-cancer therapies. Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. In addition, it is now accepted that cancers can arise from and be maintained by the cancer stem cells (CSC) or tumor-initiating cells (TIC), commonly expanded in vitro as tumorspheres from several solid tumors, including melanoma (melanospheres). Here, we investigated the potential targeting of MEK pathway by exploiting highly reliable in vitro and in vivo pre-clinical models of melanomas based on melanospheres, as melanoma initiating cells (MIC) surrogates. MEK inhibition, through PD0325901, provided a successful strategy to affect survival of mutated-BRAF melanospheres and growth of wild type-BRAF melanospheres. A marked citotoxicity was observed in differentated melanoma cells regardless BRAF mutational status. PD0325901 treatment, dramatically inhibited growth of melanosphere-generated xenografts and determined impaired tumor vascularization of both mutated- and wild type-BRAF tumors, in the absence of mice toxicity. These results suggest that MEK inhibition might represent a valid treatment option for patients with both mutated- or wild type-BRAF melanomas, affecting tumor growth through multiple targets. PMID- 24238214 TI - Effect of Crown to Implant Ratio and Anatomical Crown Length on Clinical Conditions in a Single Implant: A Retrospective Cohort Study. AB - PURPOSE: The aim of this retrospective cohort study was to evaluate the long-term influence of the crown-to-implant (C/I) ratio and anatomical crown length on clinical conditions around Astra single dental implants placed in the premolar and molar regions. MATERIALS AND METHODS: Seventy-six subjects were selected from patients who had been treated with single Astra implants for replacement of missing premolars and molars. The peri-implant marginal bone level change was assessed 1 year after functional loading and 6 years after functional loading. To predict the peri-implant marginal bone level change using clinical and radiographic data, a multiple linear regression model was applied. The Wilcoxon rank sum test was used to analyze difference median in technical complications. RESULTS: The C/I ratio and anatomical crown length were not associated with peri implant marginal bone loss or changes in the bone level at 6 years (p = .48, p = .31). However, the modified plaque index, modified sulcus bleeding index, and smoking status influenced the peri-implant marginal bone loss (p < .05, r(2) = 0.54). In addition, the patient with technical complication group did show significantly increased anatomical crown length (p < .05) CONCLUSIONS: The higher C/I ratio and anatomical crown length did not increase the risk of peri-implant marginal bone loss during 6 years of functional loading. In addition, higher anatomical crown lengths are associated with higher technical complications. PMID- 24238216 TI - Fatalities in wingsuit BASE jumping. AB - OBJECTIVE: To analyze fatality data associated with wingsuit use in an international case series of fixed-object sport parachuting (BASE jumping) to identify incident and injury mechanisms and to form a basis for potential prevention measures and future safety recommendations. METHODS: A descriptive epidemiological study was performed of fatal injury events occurring in wingsuit BASE jumping. Fatalities (n = 180) were sequentially analyzed assessing human, equipment, and environmental factors from 1981 to 2011. Main outcome measures included descriptions of typical fatal incident and injury mechanisms. RESULTS: Of the 180 fatal events, 39 (22%) were related to use of wingsuits; 38 (97%) launched from cliffs and 1 (3%) from a building. Of the 39 fatalities, 19 (49%) were caused from cliff strikes, 18 (46%) from ground impact, and 1 (3%) from a building strike. Thirty-eight (97%) of the fatalities were male. During 2002 to 2007 there was a total of 61 BASE jumping deaths, 10 (16%) of which were related to the use of wingsuits, whereas during 2008 to 2011 there was a total 59 fatal events, of which 29 (49%) were related to the use of wingsuits. Seventeen fatalities (39%) were attributed to wingsuit path miscalculation. In the first 8 months of 2013, 17 of 19 (90%) fatalities were wingsuit related. Most fatalities occurred between April and October, reflecting a seasonal increase in activity in the northern hemisphere summer. CONCLUSIONS: Wingsuit-related BASE jump fatalities appear to be increasing as wingsuit BASE jumping increases in popularity. Most fatalities are attributed to cliff or ground impact, and are mostly the result of flying path miscalculation. PMID- 24238215 TI - Profile of infective endocarditis observed from 2003 - 2010 in a single center in Italy. AB - BACKGROUND: This study aimed to provide a contemporary picture of the epidemiologic, clinical, microbiologic characteristics and in-hospital outcome of infective endocarditis (IE) observed in a single center in Italy. METHODS: We performed a retrospective study of patients with definite or probable IE observed at the "L. Sacco" Hospital in Milan, Italy, from January 1, 2003 through December 31, 2010. RESULTS: 189 episodes of IE in 166 patients were included. The mean number of incident IE in the study period was of 1.27 (range 0.59-1.76) cases per 1000 patients admitted. The median age of the cohort was 57 (interquartile range, 43-72) years, 63% were male and 62.5% had native valve IE. Twenty-six percent were active intravenous drug users (IVDU), 29% had a health care-associated IE and 5% chronic rheumatic disease. Twenty-nine percent of the cases occurred in patients affected by chronic liver disease and 19% in HIV positive subjects. Staphylococcus aureus was the most common pathogen (30%), followed by streptococci. The mitral (34%) and aortic (31%) valves were involved most frequently. The following complications were common: stroke (19%), non-stroke embolizations (25%), heart failure (26%) and intracardiac abscess (9%). Surgical treatment was frequently employed (52%) but in hospital mortality remained high (17%). Health care-associated IE and complications were independently associated with an increased risk of in-hospital death, while surgery was associated with decreased mortality. CONCLUSION: S. aureus emerged as the leading causative organism of IE in a University hospital in northern Italy. Our study confirmed the high in-hospital mortality of IE, particularly if health care associated, and the protective role of surgery. PMID- 24238217 TI - Effect of caffeine intake on finger cold-induced vasodilation. AB - OBJECTIVE: The purpose of the study was to investigate the effect of caffeine intake on finger cold-induced vasodilation (CIVD). METHODS: Ten healthy men underwent 6 experimental trials characterized by control (NCAFF) or caffeine intake (CAFF) via chewing gum (300 mg of caffeine) while resting on a chair or performing submaximal (70% maximal oxygen consumption) or maximal (100% maximal oxygen consumption) treadmill exercise (Bruce protocol) followed by immersion of the middle finger in a water bath (5 degrees C) for 20 minutes. Finger temperature (Tf ) and time parameters of the first CIVD cycle and post-test norepinephrine were measured. RESULTS: Exercise duration for submaximal and maximal exercise was 8.9 +/- 0.9 and 12.4 +/- 0.8 minutes, respectively. CAFF had no effect on Tf, but exercise increased minimal Tf in NCAFF (9.08 +/- 1.27 degrees C, 13.02 +/- 2.13 degrees C, and 13.25 +/- 1.63 degrees C in rest, submaximal, and maximal exercise, respectively) and CAFF (8.76 +/- 1.39 degrees C, 12.50 +/- 1.91 degrees C, and 12.79 +/- 1.20 degrees C). Maximal Tf was significantly higher in NCAFF (15.98 +/- 1.04 degrees C, 16.18 +/- 1.56 degrees C, and 15.14 +/- 1.52 degrees C) than in CAFF (13.56 +/- 1.19 degrees C, 15.52 +/ 1.31 degrees C, and 14.39 +/- 1.43 degrees C), resulting in a significant difference between minimal and maximal Tf in rest (NCAFF, 6.89 +/- 1.56 degrees C and CAFF, 4.79 +/- 1.23 degrees C), but not in exercise conditions. CAFF had no effect on CIVD time responses, but exercise significantly shortened CIVD onset and peak time compared with rest in both NCAFF and CAFF. Norepinephrine concentration was significantly greater in CAFF (290.6 +/- 113.0 pg/mL, 278.1 +/- 91.4 pg/mL, and 399.8 +/- 125.5 pg/mL) than NCAFF (105.6 +/- 29.5 pg/mL, 199.6 +/ 89.6 pg/mL, and 361.5 +/- 171.3 pg/mL). CONCLUSIONS: Caffeine intake before finger immersion in cold water does not result in a thermogenic effect and adversely affects CIVD responses, whereas exercise modifies CIVD temperature and time responses. PMID- 24238218 TI - Halomonas sulfidaeris-dominated microbial community inhabits a 1.8 km-deep subsurface Cambrian Sandstone reservoir. AB - A low-diversity microbial community, dominated by the gamma-proteobacterium Halomonas sulfidaeris, was detected in samples of warm saline formation porewater collected from the Cambrian Mt. Simon Sandstone in the Illinois Basin of the North American Midcontinent (1.8 km/5872 ft burial depth, 50 degrees C, pH 8, 181 bars pressure). These highly porous and permeable quartz arenite sandstones are directly analogous to reservoirs around the world targeted for large-scale hydrocarbon extraction, as well as subsurface gas and carbon storage. A new downhole low-contamination subsurface sampling probe was used to collect in situ formation water samples for microbial environmental metagenomic analyses. Multiple lines of evidence suggest that this H. sulfidaeris-dominated subsurface microbial community is indigenous and not derived from drilling mud microbial contamination. Data to support this includes V1-V3 pyrosequencing of formation water and drilling mud, as well as comparison with previously published microbial analyses of drilling muds in other sites. Metabolic pathway reconstruction, constrained by the geology, geochemistry and present-day environmental conditions of the Mt. Simon Sandstone, implies that H. sulfidaeris-dominated subsurface microbial community may utilize iron and nitrogen metabolisms and extensively recycle indigenous nutrients and substrates. The presence of aromatic compound metabolic pathways suggests this microbial community can readily adapt to and survive subsurface hydrocarbon migration. PMID- 24238221 TI - Differences in ocular parameters between diurnal and nocturnal raptors. AB - OBJECTIVE: To establish and compare normal ocular parameters between and within diurnal and nocturnal raptor groups. ANIMALS STUDIED: Eighty-eight ophthalmically normal raptors of six nocturnal and 11 diurnal species were studied. PROCEDURE: Tear production was measured using Schirmer tear test (STT) and phenol red thread test (PRTT), and applanation tonometry was conducted. Ultrasonographic measurements of axial length (AL), mediolateral axis (ML), vitreous body (VB), and pecten length (PL) were recorded, and conjunctival cultures were obtained. RESULTS: A weak correlation (R = 0.312, P = 0.006) was found between PRTT and STT. Tear production was significantly lower in nocturnal species (P < 0.001), but no difference was observed in intraocular pressure (IOP). VB and PL were significantly longer in diurnals (P < 0.001 and P = 0.021, respectively), and no significant difference was observed in AL and ML. When comparing results within these groups, there was a significant difference between most species for all parameters except IOP. Fifty-one percent of the examined raptors were positive for mycology or bacteriology, either on culture or PCR. The most common infectious agent isolated was Staphylococcus spp. CONCLUSIONS: Phenol red thread test and STT are both valid methods to measure tear production; however, a separate baseline must be determined for each species using these methods, as the results of one method cannot be extrapolated to the other. Due to significant differences observed within diurnal and nocturnal species, it appears that a more intricate division should be used when comparing these parameters for raptors, and the classification of diurnal or nocturnal holds little significance in the baseline of these data. PMID- 24238220 TI - Amino-terminal fragments of laminin gamma2 chain retract vascular endothelial cells and increase vascular permeability. AB - Laminin gamma2 (Lmgamma2) chain, a subunit of laminin-332, is a typical molecular marker of invading cancer cells, and its expression correlates with poor prognosis of cancer patients. It was previously found that forced expression of Lmgamma2 in cancer cells promotes their invasive growth in nude mice. However, the mechanism of the tumor-promoting activity of Lmgamma2 remains unknown. Here we investigated the interaction between Lmgamma2 and vascular endothelial cells. When treated with an N-terminal proteolytic fragment of gamma2 (gamma2pf), HUVECs became markedly retracted or shrunken. The overexpression of Lmgamma2 or treatment with gamma2pf stimulated T-24 bladder carcinoma cells to invade into the HUVEC monolayer and enhanced their transendothelial migration in vitro. Moreover, gamma2pf increased endothelial permeability in vitro and in vivo. As the possible mechanisms, gamma2pf activated ERK and p38 MAPK but inactivated Akt in HUVECs. Such effects of gamma2pf led to prominent actin stress fiber formation in HUVECs, which was blocked by a ROCK inhibitor. In addition, gamma2pf induced delocalization of VE-cadherin and beta-catenin from the intercellular junction. As possible receptors, gamma2pf interacted with heparan sulfate proteoglycans on the surface of HUVECs. Moreover, we localized the active site of gamma2pf to the N-terminal epidermal growth factor-like repeat. These data suggest that the interaction between gamma2pf and heparan sulfate proteoglycans induces cytoskeletal changes of endothelial cells, leading to the loss of endothelial barrier function and the enhanced transendothelial migration of cancer cells. These activities of Lmgamma2 seem to support the aberrant growth of cancer cells. PMID- 24238219 TI - Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations. AB - BACKGROUND: Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC. METHODS: Microarray experiments were performed with custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary RCC tumors and 11 nontumor adjacent matched tissues were analyzed. Meta-analyses were performed with microarray expression data from three additional human tissues (normal liver, prostate tumor and kidney nontumor samples), and with large-scale public data for epigenetic regulatory marks and for evolutionarily conserved sequences. RESULTS: A signature of 29 intronic lncRNAs differentially expressed between RCC and nontumor samples was obtained (false discovery rate (FDR) < 5%). A signature of 26 intronic lncRNAs significantly correlated with the RCC five-year patient survival outcome was identified (FDR < 5%, p-value <= 0.01). We identified 4303 intronic antisense lncRNAs expressed in RCC, of which 22% were significantly (p < 0.05) cis correlated with the expression of the mRNA in the same locus across RCC and three other human tissues. Gene Ontology (GO) analysis of those loci pointed to 'regulation of biological processes' as the main enriched category. A module map analysis of the protein-coding genes significantly (p < 0.05) trans correlated with the 20% most abundant lncRNAs, identified 51 enriched GO terms (p < 0.05). We determined that 60% of the expressed lncRNAs are evolutionarily conserved. At the genomic loci containing the intronic RCC-expressed lncRNAs, a strong association (p < 0.001) was found between their transcription start sites and genomic marks such as CpG islands, RNA Pol II binding and histones methylation and acetylation. CONCLUSION: Intronic antisense lncRNAs are widely expressed in RCC tumors. Some of them are significantly altered in RCC in comparison with nontumor samples. The majority of these lncRNAs is evolutionarily conserved and possibly modulated by epigenetic modifications. Our data suggest that these RCC lncRNAs may contribute to the complex network of regulatory RNAs playing a role in renal cell malignant transformation. PMID- 24238223 TI - Editorial overview. System immunology. PMID- 24238222 TI - Child, neglect and oral health. AB - BACKGROUND: Despite advancements in oral health policies, dental caries still a problem. The lack of parents/caregiver's care regarding child's oral health, which characterizes neglect, may lead to a high prevalence of caries. Therefore, the objective of this study was to analyze the relation between dental caries and neglect in five year-old children. METHODS: Quantitative study performed in two different moments. First, the children underwent oral examinations and physical inspection. Then, a semi-structured interview was performed with parents of children with high and low caries rate. RESULTS: In all, 149 physical inspections and oral exams were performed. The number of decayed, missing and filled teeth - dmf-t was 2.75 (SD 2.83); 16 children had extremely high values (dmf-t >= 7), 85 intermediate values (1 <= dmf-t >= 6) and 48 extremely low (dmf-t = 0). Nearly all caregivers were female (96.7%; n = 29), mostly mothers (93.3%; n = 28). Associations were found between caries experience and reason of the last consultation (p = 0.011), decayed teeth and child's oral health perception (p = 0.001). There was a trend towards a significant association between general health and decayed teeth (p = 0.079), general hygiene and caries experience (p = 0.083), and caries experience and number of times the child brushes the teeth (p = 0.086). CONCLUSION: There's a relation between caries experience and children's oral health perception by caregivers, as well as between caries experience and children's access to dental care. There is a trend towards association between caries experience and risk factors suggestive of neglect. PMID- 24238226 TI - Screening for lung cancer with low-dose CT scans. PMID- 24238225 TI - The DIAMOND initiative: implementing collaborative care for depression in 75 primary care clinics. AB - BACKGROUND: The many randomized trials of the collaborative care model for improving depression in primary care have not described the implementation and maintenance of this model. This paper reports how and the degree to which collaborative care process changes were implemented and maintained for the 75 primary care clinics participating in the DIAMOND Initiative (Depression Improvement Across Minnesota-Offering a New Direction). METHODS: Each clinic was trained to implement seven components of the model and participated in ongoing evaluation and facilitation activities. For this study, assessment of clinical process implementation was accomplished via completion of surveys by the physician leader and clinic manager of each clinic site at three points in time. The physician leader of each clinic completed a survey measure of the presence of various practice systems prior to and one and two years after implementation. Clinic managers also completed a survey of organizational readiness and the strategies used for implementation. RESULTS: Survey response rates were 96% to 100%. The systems survey confirmed a very high degree of implementation (with large variation) of DIAMOND depression practice systems (mean of 24.4 +/- 14.6%) present at baseline, 57.0 +/- 21.0% at one year (P = <0.0001), and 55.9 +/- 21.3% at two years. There was a similarly large increase (and variation) in the use of various quality improvement strategies for depression (mean of 29.6 +/- 28.1% at baseline, 75.1 +/- 22.3% at one year (P = <0.0001), and 74.6 +/- 23.0% at two years. CONCLUSIONS: This study demonstrates that under the right circumstances, primary care clinics that are prepared to implement evidence-based care can do so if financial barriers are reduced, effective training and facilitation are provided, and the new design introduces the specific mental models, new care processes, and workers and expertise that are needed. Implementation was associated with a marked increase in the number of improvement strategies used, but actual care and outcomes data are needed to associate these changes with patient outcomes and patient-reported care. PMID- 24238224 TI - The planarian regeneration transcriptome reveals a shared but temporally shifted regulatory program between opposing head and tail scenarios. AB - BACKGROUND: Planarians can regenerate entire animals from a small fragment of the body. The regenerating fragment is able to create new tissues and remodel existing tissues to form a complete animal. Thus different fragments with very different starting components eventually converge on the same solution. In this study, we performed an extensive RNA-seq time-course on regenerating head and tail fragments to observe the differences and similarities of the transcriptional landscape between head and tail fragments during regeneration. RESULTS: We have consolidated existing transcriptomic data for S. mediterranea to generate a high confidence set of transcripts for use in genome wide expression studies. We performed a RNA-seq time-course on regenerating head and tail fragments from 0 hours to 3 days. We found that the transcriptome profiles of head and tail regeneration were very different at the start of regeneration; however, an unexpected convergence of transcriptional profiles occurred at 48 hours when head and tail fragments are still morphologically distinct. By comparing differentially expressed transcripts at various time-points, we revealed that this divergence/convergence pattern is caused by a shared regulatory program that runs early in heads and later in tails.Additionally, we also performed RNA-seq on smed-prep(RNAi) tail fragments which ultimately fail to regenerate anterior structures. We find the gene regulation program in response to smed-prep(RNAi) to display the opposite regulatory trend compared to the previously mentioned share regulatory program during regeneration. Using annotation data and comparative approaches, we also identified a set of approximately 4,800 triclad specific transcripts that were enriched amongst the genes displaying differential expression during the regeneration time-course. CONCLUSION: The regeneration transcriptome of head and tail regeneration provides us with a rich resource for investigating the global expression changes that occurs during regeneration. We show that very different regenerative scenarios utilize a shared core regenerative program. Furthermore, our consolidated transcriptome and annotations allowed us to identity triclad specific transcripts that are enriched within this core regulatory program. Our data support the hypothesis that both conserved aspects of animal developmental programs and recent evolutionarily innovations work in concert to control regeneration. PMID- 24238227 TI - Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan. AB - Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patient's head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug resistant infection following a tsunami disaster. PMID- 24238228 TI - Development of pulmonary alveolar proteinosis following exposure to dust after the Great East Japan Earthquake. AB - We report a unique case of pulmonary alveolar proteinosis that developed 3 weeks after the Great East Japan Earthquake and the subsequent tsunami. The patient had inhaled dust repeatedly while visiting her devastated neighborhood without wearing a protective mask. Five weeks after the earthquake, lung samples taken from the patient showed foreign particle deposition; however, her serum was negative for GM-CSF autoantibody. The patient's clinical symptoms resolved following whole lung lavage. We conclude that inhalation of fine dust particles after natural disasters may cause the onset of pulmonary alveolar proteinosis. PMID- 24238229 TI - Importance of clinical epidemiology research in studies on respiratory diseases. AB - Evidence-based medicine (EBM) has generated great interest since the 1990s and many physicians worldwide have based their clinical practice on this idea. Its underlying concepts include a diverse array of findings from clinical epidemiological research. In western countries, many clinical databases of clinical epidemiology are in circulation. Clinical epidemiological research using these data in western countries constitutes the majority worldwide. However, because race, lifestyle, culture, etc., differ among western countries and Japan, it is difficult to apply the results of clinical epidemiological research obtained in Japan to western countries. Unfortunately, there is no large-scale database for respiratory diseases prevalent in Japan. Many specialists agree with the opinion that it is necessary to collect medical information specific to the Japanese population and analyze the clinical data. KiHAC (Kinki Hokuriku Airway Disease Conference) was established in September 2001 with the aim of generating evidence through clinical epidemiological research for airway diseases by targeting physicians practicing respiratory medicine, pediatrics, and otorhinolaryngology, primarily in the Kinki and Hokuriku regions located in the central to western parts of Japan. As a part of the KiHAC, clinical research societies will attempt to cooperate with each other to make joint research possible and to share and utilize information, in addition to further promoting clinical research in the field of respiratory medicine. PMID- 24238230 TI - Can preoperative imaging studies accurately predict the occurrence of bullae or blebs? Correlation between preoperative radiological and intraoperative findings. AB - BACKGROUND: Radiological findings of patients with primary spontaneous pneumothorax (PSP) undergoing surgery have not been well analyzed. The aim of this study was to evaluate the accuracy of imaging studies for predicting the presence of emphysema-like changes (ELCs) detectable during surgery. METHODS: Ninety-three PSP patients who underwent surgery from September 2005 to October 2009 were included in the study. We analyzed preoperative chest radiographic and computed tomographic (CT) findings, and compared the findings with intraoperative detection of ELCs. Chest radiographic findings were analyzed by classifying the PSP size into three categories: small, moderate, and complete. RESULTS: Seventy six of the 93 patients (82%) had ELCs detected during surgery. The size of the PSP on a radiograph was significantly correlated with the presence of ELCs (p=0.0121). Preoperative CT revealed 64 of the 76 ELCs (sensitivity, 84%; specificity, 100%; accuracy, 87%). Twenty-nine patients without ELCs detected by preoperative CT were analyzed separately. In this group, a larger PSP size also increased the likelihood of ELCs being present (p=0.0049). Seven patients (8%) experienced a recurrence after surgery. No factor could significantly predict recurrence. CONCLUSIONS: Chest CT analysis alone was associated with a false negative rate of about 15% for ELCs. Combining the analysis of chest radiographic and CT findings could improve sensitivity. PMID- 24238231 TI - A change in the number of CCSP(pos)/SPC(pos) cells in mouse lung during development, growth, and repair. AB - BACKGROUND: Putative resident stem/progenitor cells have been identified in the bronchoalveolar duct junction (BADJ) of the murine lung. However, the contribution of stem cells expressing both Clara cell secretory protein (CCSP) and pro-surfactant protein C (SP-C) to the repair and maintenance of normal homeostasis is still unclear. In this study, we identified and then quantified CD45(neg)/CCSP(pos)/SP-C(pos) cell numbers in normal and lung-injured mice. METHODS: Normal lung tissues of fetal, newborn, and adult mice were used to evaluate lung progenitor cells during development and growth. Mice treated with naphthalene were used for the bronchiolar epithelium injury model, and mice treated with bleomycin were used for the alveolar epithelium injury model. These lung tissues were stained with CD45, CCSP, and SP-C antibodies by immunofluorescence. The number of lung progenitor cells was counted as CD45(neg)/CCSP(pos)/SP-C(pos) cells by flow cytometry. RESULTS: CCSP(pos)/SP C(pos) epithelial cells in the BADJ were identified from E18 to 7 months after birth. The percentage of CD45(neg)/CCSP(pos)/SP-C(pos) cells was relatively stable to 7 months (between 0.3+/-0.04% and 1.28+/-0.11%). When lungs were treated with naphthalene, the proliferation of CCSP(pos)/SP-C(pos) cells was observed as patches of double-positive cells and preceded the recovery of bronchioles. In contrast, when lungs were treated with bleomycin, the proliferation of CCSP(pos)/SP-C(pos) cells was observed, but the type II alveolar epithelial cells never recovered to baseline. CONCLUSIONS: CCSP(pos)/SP-C(pos) lung cells were stable until 7 months after birth. These cells in the BADJ primarily regenerate bronchiolar epithelial cells and not alveolar epithelial cells. PMID- 24238233 TI - Habitual physical activity score as a predictor of the 6-min walk test distance in healthy adults. AB - BACKGROUND: The 6-min walk test (6MWT) is a simple, inexpensive test of functional exercise capacity. The 6MWT distance (6MWD) in healthy adults varies geographically, emphasizing the need for population-specific reference equations. The purpose of the present study was to investigate the influences of the habitual physical activity (HPA) score and other anthropometric and demographic parameters on the variability of the 6MWD among healthy adults and to propose a reference equation. METHODS: This was a prospective, cross-sectional, observational study. The 6MWT was conducted in a 30-m hospital corridor on 201 healthy volunteers, 125 men and 76 women, aged 20-60 years. The HPA in the previous 6 months was assessed using Baecke's questionnaire. Univariate analysis followed by multiple regression analysis was performed to analyze the significance levels of different probable predictors. RESULTS: The 6MWD was significantly greater in more active than in less active subjects (663.8+/-55.4m vs. 599.9+/-67.8m, p<0.001). The regression analysis showed that the subject's age in years (p=0.017), gender (p=0.006), height in cm (p=0.004), weight in kg (p<0.001), total activity score (TS) (p<0.001), and absolute difference in heart rate before and after exercise (p<0.001) could explain 48.9% of the variability in the 6MWD in healthy adults. CONCLUSIONS: The HPA score is probably the most appropriate variable to include in the reference equation predicting the 6MWD in healthy adults from the Indian subcontinent. PMID- 24238232 TI - Targeted reduction of CCR4+ cells is sufficient to suppress allergic airway inflammation. AB - BACKGROUND: Bronchial asthma is characterized by allergic airway inflammation involving C-C chemokine receptor type 4 (CCR4)-positive Th2 cells. As such, we hypothesize that the disease can be alleviated by targeted-elimination of CCR4+ cells. Thymus and activation-regulated chemokine (TARC)-PE38, a TARC fused the exotoxin fragment PE38 from Pseudomonas aeruginosa, has been shown to efficiently kill CCR4+ cells by delivering the exotoxin fragment PE38 into CCR4+ cells. To test our hypothesis, we examined whether TARC-PE38 could suppress allergic airway inflammation in a mouse model of house dust mite (HDM)-induced allergic airway inflammation. METHODS: We evaluated the effect of TARC-PE38 on the major characteristics of HDM-induced allergic airway inflammation. Airway hyperresponsiveness, lung histopathology, lung Th1/Th2 cell populations, and concentrations of Th1/Th2 cytokines in the lungs were assessed in HDM-sensitized and challenged mice in the presence and absence of TARC-PE38. RESULTS: TARC-PE38 efficiently suppressed allergic airway inflammation by significantly reducing airway hyperresponsiveness, the overall area of inflammation, and goblet cell hyperplasia. In HDM-sensitized and challenged mice, TARC-PE38 specifically reduced the numbers of CCR4+ cells. This reduction was associated with a significant decrease in the production of Th2 cytokines in the airway,and a decrease in the number of leukocytes, including macrophages, eosinophils and lymphocytes, within the subepithelial area of the lungs and airway lumen. TARC PE38 had noeffect on Th1 cells. CONCLUSION: Our data suggest that the elimination of CCR4+ cells via TARC-PE38 treatment is sufficient to control allergic airway inflammation and airway hyperresponsiveness. PMID- 24238234 TI - Use of macrolides in the 2009 H1N1 virus infection outbreak: a survey of general practices in Japan. PMID- 24238235 TI - Consensus statement for the diagnosis and treatment of drug-induced lung injuries. PMID- 24238236 TI - Massive calcinosis and severe osteoporosis in paediatric-onset overlap syndrome. PMID- 24238237 TI - [Lung tumors: an evolving histopathology!]. PMID- 24238238 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Introduction]. PMID- 24238239 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 1: Poorly differentiated non small cell lung carcinoma: interpretation of small biopsy specimens]. PMID- 24238240 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 2: Basaloid carcinoma]. PMID- 24238241 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 3. Sarcomatoid carcinoma, pleiomorphic type]. PMID- 24238242 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 4: Pleural metastasis of sarcomatoid carcinoma]. PMID- 24238243 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 5: Lymph node metastasis of an atypical carcinoid]. PMID- 24238244 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 6: Large cell neuroendocrine carcinoma combined]. PMID- 24238245 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 7: Pulmonary adenoid cystic carcinomas]. PMID- 24238246 TI - [2014 classification of lung carcinomas: latest entities and clinical implications. Case 8: Pulmonary mucoepidermoid carcinomas]. PMID- 24238247 TI - [Anal verruciform xanthoma in a transplant background for primary hyperoxaluria. Anal verruciform xanthoma after a combined hepato-renal transplantation]. AB - We report a case of anal verruciform xanthoma in a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria. Verruciform xanthoma is a rare and benign lesion arising in oral cavity and genital mucosa. It is characterized pathologically by papillary epithelial hyperplasia and aggregates of foamy macrophages in connective tissue papillae. This condition, whose pathogenesis remains unclear, has been reported in immunosuppressive background or associated with underlying dermatosis. We report here the second case of anal verruciform xanthoma. To our knowledge, this is the first report of verruciform xanthoma in association with primary hyperoxaluria. PMID- 24238248 TI - [Fetal cytomegalovirus infection diagnosed on autopsy: a case report]. AB - The cytomegalovirus (CMV) is the most common maternal-fetal transmission infectious disease. The diagnosis of this infection is rarely made on antenatal sonographic signs. Pathological examination could, in this case, make etiologic diagnosis. We report the case of a terminated pregnancy, at the term of 19 weeks of gestation, occurring in a 31-year-old woman. The sonography found a terminated pregnancy with anamnios. Histological examination of samples of fetal internal organs showed intranuclear inclusions, compatible with CMV infection. The main objective of our work is to emphasize the value of histological examination in the diagnosis of fetal death etiology. Moreover, we will discuss the benefit of antenatal screening of CMV maternal infection. PMID- 24238249 TI - [A "lymph node" of the hepatic hilum]. PMID- 24238250 TI - [An unusual endobronchial tumor]. PMID- 24238252 TI - [Warty pigmented papules in an infant]. PMID- 24238251 TI - [Very rare cause of diffuse goiter]. PMID- 24238253 TI - [Subcutaneous lesion of a newborn]. PMID- 24238254 TI - [About a prevalent cervical node metastasis]. PMID- 24238255 TI - [Very rare parotidian tumor]. PMID- 24238256 TI - Retinal nerve fibre layer cross-sectional area, neuroretinal rim area and body mass index. AB - PURPOSE: To examine associations between body mass index, neuroretinal rim area and retinal nerve fibre layer cross-sectional area (RNFLCRA) in a population based setting. METHODS: The Central India Eye and Medical Study is a population based study performed in a rural region of Central India. The study included 4711 subjects (aged 30 + years). A detailed ophthalmic and medical examination was performed. Inclusion criteria for this study were an intra-ocular pressure <=21 mmHg, open anterior chamber angles and an axial length <=26.5 mm. Neuroretinal rim area and RNFLCRA were measured by confocal laser scanning tomography. RESULTS: The study included 3959 subjects fulfilling the inclusion criteria. Larger neuroretinal rim area (mean: 1.63 +/- 0.32 mm(2) ) was significantly (p = 0.004) associated with a higher body mass index after adjusting for larger disc area (p < 0.001), younger age (p < 0.001), lower intraocular pressure (p < 0.001), and hyperopic refractive error (p < 0.001). Larger retinal nerve fibre layer cross-sectional area (mean:1.29 +/- 0.39 mm(2) ) was significantly associated with higher body mass index (p = 0.001) after adjusting for younger age (p < 0.001), shorter axial length (p < 0.001), larger optic disc area (p < 0.001), taller body height (p < 0.001) and male gender (p = 0.04). CONCLUSIONS: In a rural Central Indian population, neuroretinal rim area and RNFLCRA as surrogates of the optic nerve fibres were related to a higher body mass index. Because body mass index is associated with cerebrospinal fluid pressure, the higher cerebrospinal fluid pressure may be associated with a larger neuroretinal rim area. It may vaguely point towards an association between cerebrospinal fluid pressure and glaucomatous optic neuropathy. PMID- 24238257 TI - Entering a new era for Chemopshere. PMID- 24238258 TI - Development of a system dynamics model for financially sustainable management of municipal watermain networks. AB - This paper develops causal loop diagrams and a system dynamics model for financially sustainable management of urban water distribution networks. The developed causal loop diagrams are a novel contribution in that it illustrates the unique characteristics and feedback loops for financially self-sustaining water distribution networks. The system dynamics model is a mathematical realization of the developed interactions among system variables over time and is comprised of three sectors namely watermains network, consumer, and finance. This is the first known development of a water distribution network system dynamics model. The watermains network sector accounts for the unique characteristics of watermain pipes such as service life, deterioration progression, pipe breaks, and water leakage. The finance sector allows for cash reserving by the utility in addition to the pay-as-you-go and borrowing strategies. The consumer sector includes controls to model water fee growth as a function of service performance and a household's financial burden due to water fees. A series of policy levers are provided that allow the impact of various financing strategies to be evaluated in terms of financial sustainability and household affordability. The model also allows for examination of the impact of different management strategies on the water fee in terms of consistency and stability over time. The paper concludes with a discussion on how the developed system dynamics water model can be used by water utilities to achieve a variety of utility short and long-term objectives and to establish realistic and defensible water utility policies. It also discusses how the model can be used by regulatory bodies, government agencies, the financial industry, and researchers. PMID- 24238259 TI - Comparisons between abiotic nitration and biotransformation reactions of phenolic micropollutants in activated sludge. AB - The transformation of selected phenolic substances was investigated during biological wastewater treatment. A main emphasis was put on the relevance of abiotic processes leading to toxic nitrophenolic transformation products (TPs). Due to their environmental relevance, the antiseptic ortho-phenylphenol (OPP), the plastics additive bisphenol A (BPA) and the psychoactive drug dextrorphan have been studied. Batch experiments confirmed that nitro- and nitroso-phenolic TPs can be formed under acidic conditions when nitrite is present. HNO2, N2O3 and NO and NO2 radicals are likely involved in the abiotic process. It was found that the process was promoted by the freezing of water samples, since this can lead to an unexpected pH drop. However, under conditions present at wastewater treatment plants (neutral pH, low nitrite concentrations), the formation of appreciable concentrations is rather unlikely through this process, since HNO2 concentrations are extremely low and NO and NO2 radicals will also react with other wastewater constituents. Thus, the transformation of phenolic substances such as OPP and BPA is mainly caused by biotic transformation. In addition to hydroxylation as a common reaction under aerobic conditions, the formation of sulfate conjugates was detected with the original compounds as well as with nitrophenolic TPs. Therefore, even when nitro-phenolic substances are formed it is likely that they are further transformed to sulfate conjugates. In raw wastewater and WWTP effluent nitrated BPA and NO2-dextrorphan were not detected. Only nitro-OPP was found in the influent of a WWTP with 2.3 ng/L, but it was not identified in the WWTP effluents. The concentrations of dextrorphan increased slightly during WWTP passage, possibly due to the cleavage of the glucuronide-conjugate, its human metabolite form, or demethylation of the prodrug dextromethorphan. PMID- 24238260 TI - Effect of sludge retention time on the biological performance of anaerobic membrane bioreactors treating corn-to-ethanol thin stillage with high lipid content. AB - The potential of anaerobic membrane bioreactors (AnMBRs) for the treatment of lipid rich corn-to-ethanol thin stillage was investigated at three different sludge retention times (SRT), i.e. 20, 30 and 50 days. The membrane assisted biomass retention in AnMBRs provided an excellent solution to sludge washout problems reported for the treatment of lipid rich wastewaters by granular sludge bed reactors. The AnMBRs achieved high COD removal efficiencies up to 99% and excellent effluent quality. Although higher organic loading rates (OLRs) up to 8.0 kg COD m(-3) d(-1) could be applied to the reactors operated at shorter SRTs, better biological degradation efficiencies, i.e. up to 83%, was achieved at increased SRTs. Severe long chain fatty acid (LCFA) inhibition was observed at 50 days SRT, possibly caused by the extensive dissolution of LCFA in the reactor broth, inhibiting the methanogenic biomass. Physicochemical mechanisms such as precipitation with divalent cations and adsorption on the sludge played an important role in the occurrence of LCFA removal, conversion, and inhibition. PMID- 24238261 TI - Population pharmacokinetic-pharmacogenetic model of tacrolimus in the early period after kidney transplantation. AB - As tacrolimus has a rather narrow therapeutic range and high individual variability in its pharmacokinetics, it is important to determine the cause of the variation in tacrolimus pharmacokinetics. The purpose of this study was to establish a population pharmacokinetic-pharmacogenetic model of tacrolimus and identify covariates that affect pharmacokinetic parameters to prevent fluctuations in the tacrolimus trough concentration during the early period after transplantation. Data from 1501 trough concentrations and 417 densely collected concentrations were compiled from 122 patients who were on post-operative days 10 20 and analysed with a nonlinear mixed-effect model. The first-order conditional estimation (FOCE) with interaction method was used to fit the model using the NONMEM program. Clinical/laboratory data were also collected for the same period, and CYP3A5 and ABCB1 genotypes were analysed for use in modelling from all included patients. An empirical Bayesian approach was used to estimate individual pharmacokinetic profiles. A one-compartment model with first absorption and elimination and lag time best described the data. The estimated population mean of clearance (CL/F), volume of distribution (V/F) and absorption rate (Ka ) were 21.9 L/hr, 205 L, and 3.43/hr, respectively, and the lag time was fixed at 0.25 hr. Clearance increased with days after transplantation and decreased with CYP3A5*3/*3 about 18.4% compared with CYP3A5*1 carriers (p < 0.001). A population pharmacokinetic model was developed for tacrolimus in early post-kidney transplantation recipients to identify covariates that affect tacrolimus pharmacokinetics. Post-operative days and CYP3A5 genotype were confirmed as critical factors of tacrolimus pharmacokinetics. PMID- 24238262 TI - Influence of d-glutamine and d-glutamic acid sequences in optical peptide probes targeted against the cholecystokinin-2/gastrin-receptor on binding affinity, specificity and pharmacokinetic properties. AB - BACKGROUND: Image-based diagnosis of tumours can be advanced and improved by targeted strategies addressing malignant molecular structures. A promising molecular target is the cholecystokinin-2-receptor (CCK2R) which can be targeted by high-affinity peptides called minigastrins. Here we present how the imaging properties of minigastrins tagged with near-infrared fluorescence (NIRF) dyes can be modulated by the introduction of different spacer sequences. We identify interactions of different probe variants with regard to target affinity, specificity and pharmacokinetic properties to optimize early detection of CCK2R expressing tumours under clinical conditions. METHODS: Two minigastrin probes with the same near-infrared hemicyanine fluorescence dye (DY-754) for signalling and the same CCK2R-binding peptide A-Y-G-W-M/Nle-N-F-amide but different spacers were designed as follows: 'QE' with three alternating d-glutamines and d-glutamic acids and 'bivQ' with two minigastrins, each preceded by three d-glutamines. They were tested for affinity and specificity in vitro on CCK2R-expressing and CCK2R non-expressing cells. In vivo imaging was conducted with subcutaneous tumour bearing nude mice after i.v. probe injection (54 to 108 nmol/kg) and under competitive conditions with non-fluorescent minigastrin (n = 5/group). We also assessed probe biodistribution as well as NIRF distribution in tumour sections. RESULTS: Both probes showed high affinity and specificity to CCK2R-expressing cells in vitro. In vivo tumour-to-background contrasts (tumour/background ratios (TBRs) of around 6) enabled identification of CCK2R-expressing tumours by both probes with low accumulation in CCK2R-negative tumours (TBR of around 2). Specificity of the in vivo accumulation, revealed by competition, was higher for QE. Besides renal retention, probe uptake into organs was very low. CONCLUSION: The properties of optical minigastrin probes can be specifically modified by the introduction of spacer sequences. A spacer of six hydrophilic amino acids increases affinity. A mix of d-glutamic and d-glutamine acids increased target-to background contrast. Multimerization could not increase affinity but supposedly lowered stability. The probe QE is a promising candidate for clinical evaluation in terms of diagnosis of CCK2R-expressing tumours. PMID- 24238263 TI - Functions of the nicotinamide adenine dinucleotide phosphate oxidase family in Ganoderma lucidum: an essential role in ganoderic acid biosynthesis regulation, hyphal branching, fruiting body development, and oxidative-stress resistance. AB - Ganoderma lucidum has drawn worldwide interest with regard to its secondary metabolism and pharmaceutical activity. However, the development of such research has been limited because of a lack of basic biological knowledge. Nicotinamide adenine dinucleotide phosphate oxidases (Nox) have recently been highlighted because of the many important biological roles in plants and animals; however, the exact functions of Nox are still not fully understood in fungi. In this study, we identified two Nox isoforms (NoxA and NoxB) and a regulator, NoxR. RNA interference was used, and silencing of the Nox isoforms and NoxR expression indicated a central role for these genes in hyphal branching, fruiting body development, reactive oxygen species (ROS) generation, ROS resistance and ganoderic acid biosynthesis regulation. Further mechanistic investigation revealed that Nox-generated ROS elevated cytosolic Ca(2+) levels by activating a plasma membrane Ca(2+) influx pathway, thereby inducing the Ca(2+) signal pathway to regulate ganoderic acid biosynthesis and hyphal branching. Importantly, our results highlight the Nox functions in signal crosstalk between ROS and Ca(2+), and these findings provide an excellent opportunity to identify the potential pathway linking ROS networks to calcium signalling in fungi and suggest that plants, animals and fungi share a conserved signal-crosstalk mechanism. PMID- 24238264 TI - Congenital adrenal hyperplasia pearls you should know--globally. PMID- 24238265 TI - Pregnancy attitudes, contraceptive service utilization, and other factors associated with Los Angeles homeless youths' use of effective contraception and withdrawal. AB - STUDY OBJECTIVE: This study aims to understand the associations of contraceptive service utilization (ie, accessing condoms or birth control), pregnancy attitudes, and lifetime pregnancy history among male and female homeless youth in relation to use of effective contraception and withdrawal. DESIGN, SETTING, AND PARTICIPANTS: Between October 2011 and February 2012, homeless youth (14-27 years old) from 2 drop-in centers in Los Angeles (N = 380) were recruited and completed a questionnaire. The data in this paper are restricted to those who reported vaginal sex at last sex (N = 283). MAIN OUTCOME MEASURES: Analyses examined history of foster care, sexual abuse, exchange sex, pregnancy, lifetime homelessness duration, current living situation, contraceptive service utilization, and pregnancy attitudes in predicting use of effective contraception and withdrawal at last sex. RESULTS: Over 62% of females and 43% of males report having ever been pregnant or impregnating someone. There are no gender-based differences in pregnancy attitudes; 21% agree they would like to become pregnant within the year. Additionally, there are no gender-based differences in reported contraceptive use at last vaginal sex. In the multivariable model, high school education, contraceptive service utilization (Relative Risk Ratio [RRR]: 4.0), and anti-pregnancy attitudes (RRR: 1.3) are significant positive predictors of using effective contraception; anti-pregnancy attitudes (RRR: 1.2) and gender (RRR: 0.3) are significantly associated with using withdrawal. CONCLUSIONS: Health professionals should acknowledge that some homeless youth desire pregnancy; for those that do not, access to effective contraception is important. Programs must continue to promote pregnancy prevention, and include discussions of healthy pregnancy habits for pregnancy-desiring youth. PMID- 24238266 TI - Study of the sexuality and demand for gynecologic services by high school students in the city of Rio de Janeiro. AB - OBJECTIVE: To identify the sexual and reproductive profile and demand for gynecologic services by high school girls in the city of Rio de Janeiro. DESIGN: Cross-sectional study carried out by administration of a questionnaire filled in by the respondents on their own, given to students at 3 high schools with different socioeconomic profiles: private, state, and federal. The questions covered socio-demographic characteristics, sexual behavior, and demand for gynecologic services. The data were analyzed by the Yates chi-square test and Student t-test, with P < .05. SETTING: Three high schools in the city of Rio de Janeiro. INTERVENTIONS: None. PARTICIPANTS: Female high school students. MAIN OUTCOME MEASURE: Age, race, socioeconomic level, parents' schooling, and sexual activity. RESULTS: A total of 418 students participated, 122 from a private school, 165 from a state public school, and 131 from a federal public school. The state school students were predominantly black and had the lowest socioeconomic level, with their parents having the fewest average years of schooling. They also reported the most sexual partners, pregnancies, and abortions. Their characteristics differed significantly from those of the private and federal school students, which were similar to each other. The average age of first sexual activity was similar for all the respondents and the first visit to a gynecologist occurred significantly later among the state school students. CONCLUSIONS: The more frequent pregnancies and abortions by the state school students can be a consequence of the lower demand for or insufficient access to gynecologic services, depriving these students of the necessary care to promote sexual and reproductive health. This demonstrates the need for public policies that promote and facilitate access to routine preventive gynecologic care by low income adolescent girls. PMID- 24238267 TI - Satisfaction with and intention to continue Depo-Provera versus the Mirena IUD among post-partum adolescents through 12 months of follow-up. AB - STUDY OBJECTIVE: No prior study has directly compared satisfaction with Depo Provera to the Mirena intra-uterine device (IUD) among post-partum parous adolescents. Our aim was to make this comparison among post-partum adolescents at 3, 6, and 12 months of follow-up. PARTICIPANTS: Post-partum/parous adolescents (aged 20 and younger) choosing either Depo-Provera or the Mirena IUD as their method of contraception. DESIGN: Prospective longitudinal survey. SETTING: The adolescent clinic at the Truman Medical Center, Kansas City Missouri. MAIN OUTCOME MEASURE: Satisfaction with and intention to continue the chosen method at 3, 6, and 12 months of follow-up. INTERVENTIONS: None. RESULTS: Sixty-six post partum/parous adolescents were recruited, 37 choosing the Mirena IUD and 29 choosing Depo-Provera for contraception. The 2 groups had similar baseline characteristics. There was no statistically significant difference in overall satisfaction with Depo-Provera versus the Mirena IUD at 3, 6, or 12 months of follow-up. For both contraceptive methods, unpredictable bleeding was most unacceptable at 6 months of follow-up but the trend was only statistically significant for Depo-Provera. For Depo-Provera, there was a significantly lower proportion of participants actually continuing the method at 12 months (42.9%) relative to the proportion who at 6 months had expressed an intention to continue (80.0%; P = .01). This trend was not seen for the Mirena IUD. CONCLUSION: Among post-partum/parous adolescents, overall subjective satisfaction with Depo-Provera and the Mirena IUD is similarly high over 12 months of follow-up. With Depo Provera, however, there appears to be a disconnect between intention to continue at 6 months and actual continuation at 12 months. PMID- 24238268 TI - Urogenital myiasis by Cordylobia anthropophaga. AB - BACKGROUND: Cordylobia anthropophaga is one of the most common agents of urogenital myiasis in African tropical regions. A case of vulvar myiasis due to the larvae of Cordylobia anthropophaga in a 16-year-old female is presented with a systematic review of the literature. CASE: A 16-year-old female with a history of recent journey to Senegal presented with a vulvar boil-like inflammatory lesion. A living insect larva was extracted from the lesion. It was identified as a Cordylobia anthropophaga larva. SUMMARY AND CONCLUSIONS: Diagnosis of vulvar myiasis must be considered if vulvar boil-like inflammatory papules are found, essentially in travelers to and from endemic countries. The diagnosis is mainly clinical and its management consists of the extraction of the larva. PMID- 24238269 TI - Caspase-1 activation is increased with human labour in foetal membranes and myometrium and mediates infection-induced interleukin-1beta secretion. AB - PROBLEM: Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that is involved in human parturition, especially in the context of infection-induced preterm birth. Caspase-1 is a key component of inflammasomes, which are activated upon infection to trigger the maturation of IL-1beta. METHOD OF STUDY: To determine the effect of human labour on caspase-1 activation in human foetal membranes and myometrium. In addition, the mechanisms by which inflammasome activation regulates IL-1beta production were also be assessed. RESULTS: Higher caspase-1 gene and protein expression were detected in foetal membranes myometrium obtained from term labouring women when compared with samples taken from non labouring women. Lipopolysaccharide induced the transcription and secretion of IL-1beta from foetal membranes and myometrium; both events were dependent on nuclear factor kappa B (NF-kappaB). However, levels of extracellular IL-1beta were greatly increased by subsequent treatment with the potassium-proton ionophore Adenosine triphosphate (ATP) or nigericin; an effect that was dependent on active caspase-1. Additionally, ATP induced IL-1beta secretion via the purinergic P2X7 receptor, whereas the pannexin-1 channel was required for nigericin induced IL-1beta secretion. CONCLUSION: Taken together, these results demonstrate that caspase-1 activation is increased with human labour in foetal membranes and myometrium, and is required for infection-induced IL-1beta secretion. PMID- 24238270 TI - Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer. AB - OBJECTIVE: Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4. DESIGN: Prospective follow-up study. SETTING: University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary). POPULATION: Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals. METHODS: Pre- and post chemotherapy computed tomography (CT) scans were performed. Serum levels of CA 125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA). MAIN OUTCOME MEASURES: Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans. RESULTS: Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients. CONCLUSIONS: Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC. PMID- 24238271 TI - Ultrasound definition of polycystic ovarian morphology: good news and bad news. PMID- 24238272 TI - Reply of the authors. PMID- 24238273 TI - Slightly lower incidence of ectopic pregnancies in frozen embryo transfer cycles versus fresh in vitro fertilization-embryo transfer cycles: a retrospective cohort study. AB - OBJECTIVE: To analyze the incidence of ectopic pregnancies (EPs) in fresh and frozen/thawed cycles. DESIGN: A retrospective cohort study on the incidence of EPs in all fresh IVF cycles from January 2002 until December 2012. This was compared with the incidence of tubal pregnancies in patients undergoing transfer of frozen/thawed embryos during the same time period. SETTING: The IVF program at Fertility Center, AZ Jan Palfijn, Gent, Belgium. PATIENT(S): A total of 11,831 patients undergoing IVF (i.e., the entire population of the IVF Center) were retrospectively analyzed. INTERVENTION(S): The IVF cycles, fresh IVF-ET, frozen/thawed ET. Laparoscopy for treatment of EP. MAIN OUTCOME MEASURE(S): Primary end point: incidence of EPs in both groups. Secondary end points: clinical pregnancy rate (PR), rate of EPs per clinical pregnancy. RESULT(S): In the fresh IVF cycle group, 10,046 patients underwent oocyte retrieval; 9,174 of them had an ET; 2,243 of these patients had a clinical pregnancy. Of these, 43 (0.47%) appeared to have an ectopic localization of their pregnancy. In the group of the patients undergoing frozen/thawed ET (1,785 patients) there were 467 pregnancies and 6 ectopic implants (0.34%). The incidence of the EPs per established clinical pregnancy was 1.92% for the fresh vs. 1.28% for the frozen/thawed cycles. CONCLUSION(S): No significant difference could be demonstrated on the incidence of EP in fresh IVF cycles vs. frozen/thawed cycles in a large cohort of patients. PMID- 24238274 TI - Haplotypes and polymorphisms of the ANXA5 nontranslated region in Japanese and European women with recurrent miscarriage and in controls. PMID- 24238275 TI - Dermatofibrosarcoma protuberans: a second primary tumor displaying Bednar and fibrosarcomatous subtypes. PMID- 24238276 TI - Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study. AB - BACKGROUND: Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups. METHODS: This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean pleural fluid ADA was significantly higher in the TPE group (100 +/- 35 IU/L) compared to non TPE patients (30 +/- 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = -0.621). For patients <= 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%. CONCLUSIONS: There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE. PMID- 24238278 TI - Long-term follow-up of sacral neuromodulation for lower urinary tract dysfunction. AB - OBJECTIVE: To report our long-term experience of sacral neuromodulation (SNM) for various lower urinary tract dysfunctions but with a focus on efficacy, safety, re interventions and degree of success. PATIENTS AND METHODS: This is a single tertiary referral centre study that included 217 patients (86% female) who received an implantable pulse generator (IPG) (InterstimTM, Medtronic, Minneapolis, USA) between 1996 and 2010. Success was considered if the initial >=50% improvement in any of primary voiding diary variables persisted compared with baseline, but was further stratified. RESULTS: The mean duration of follow up was 46.88 months. Success and cure rates were ~70% and 20% for urgency incontinence, 68% and 33% for urgency frequency syndrome and 73% and 58% for idiopathic retention. In those patients with an unsuccessful therapy outcome, the mean time to failure was 24.6 months after implantation. There were 88 (41%) patients who had at least one device or treatment related surgical re intervention. The re-intervention rate was 1.7 per patient with most of them (47%) occurring <=2 years of follow-up. CONCLUSIONS: SNM appears effective in the long-term with a success rate after definitive IPG implant of ~70% and complete cure rates ranging between 20% and 58% depending on indication. Patients with idiopathic retention appear to do best. The re-intervention rate is high with most occurring <=2 years of implantation. It is likely that with the newer techniques used, efficacy and re-intervention rates will improve. PMID- 24238277 TI - Enhanced susceptibility of B lymphoma cells to measles virus by Epstein-Barr virus type III latency that upregulates CD150/signaling lymphocytic activation molecule. AB - Measles virus (MV) is one of the candidates for the application of oncolytic virotherapy (OVT). Although an advanced clinical study has been reported on a T cell lymphoma, the potential of MV OVT against B-cell lymphomas remains to be clarified. We found that an EBV-transformed B lymphoblastoid cell line, a model for diffuse large B-cell lymphoma, and EBV-positive Burkitt's lymphoma cells bearing type III latency were highly susceptible to the cytolysis induced by an MV vaccine strain CAM-70. As analyzed by EBV-positive and -negative counterparts of the same cytogenetic background, type III EBV latency, not type I, was shown to augment the susceptibility of B lymphoma cells to MV-induced cytolysis. Cell surface levels of CD150/signaling lymphocytic activation molecule, a receptor of MV, were upregulated in B lymphoma cell lines with type III EBV latency by 3.8 fold, on average. The cytolytic activity of CD150-tropic WT MV was akin to that of CD46- and CD150-tropic CAM-70, suggesting that CD150 is critical for the susceptibility to MV-induced cytolysis. Among EBV-encoded genes, latent membrane protein 1 was responsible for the CD150 upregulation. It was notable that the majority of B lymphoma cell lines of type III EBV latency showed higher susceptibility to the non-Edmonston-derived CAM-70 than to the Edmonston-derived Schwarz strain. This is the first report indicating the potential of non Edmonston MV strain for the application of OVT. Furthermore, a cellular regulator of MV replication was implicated that functions in a vaccine strain-specific fashion. Altogether, the MV OVT should serve as an alternative therapy against EBV-positive diffuse large B-cell lymphoma with type III EBV latency. PMID- 24238279 TI - Agreement between Histomorphometry and Microcomputed Tomography to Assess Bone Microarchitecture of Dental Implant Sites. AB - BACKGROUND: Histomorphometry and microcomputed tomography (microCT) have been used in implant studies but need better understanding before being used as equivalent methods. PURPOSE: The purpose of this study was to investigate the agreement between 2D (histomorphometry) and 3D (microCT) reference methods for assessing jawbone microarchitecture in vivo. MATERIAL AND METHODS: Forty-four bone specimens from 32 patients were obtained during implant placement and examined by microCT, followed by hematoxylin-eosin staining and histomorphometric analysis. The morphometric parameters included bone volume density (BV/TV), bone surface fraction (BS/TV), bone surface density, trabecular thickness, trabecular number, and trabecular separation (Tb.Sp). Bland-Altman plots were used for pairwise agreement analysis between the equivalent 3D and 2D parameters, and complemented with Mountain plots. The association between the two methods was tested using Pearson's correlation followed by Passing-Bablok regression. RESULTS: Systematic bias was observed in all Bland-Altman and Mountain plots, including constant bias for BV/TV and Tb.Sp, and proportional bias for all other parameters. Significant correlation was found for BV/TV (r = 0.80; p < .001) and BS/TV (r = 0.44; p = .003), and the Passing-Bablok regression showed constant bias for BV/TV and proportional bias for BS/TV. CONCLUSION: Because of the poor agreement between measures obtained by histomorphometry and microCT, these methods should not be used interchangeably for jawbones. PMID- 24238280 TI - Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis. AB - BACKGROUND: Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors' technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime. METHODS: Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient's perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded. RESULTS: 28 female and four male patients (mean age 14.5 +/- 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. CONCLUSIONS: Local anaesthetic administration via an intrapleural catheter is a safe and effective method of analgesia following thoracoscopic anterior scoliosis correction. Post-operative pain following anterior thoracic scoliosis surgery can be reduced to 'mild' levels by combined analgesia regimes. PMID- 24238281 TI - Clinical and serological findings associated with the expression of ITGAL, PRF1, and CD70 in systemic lupus erythematosus. AB - We determined the expression of Integrin alpha L chain (ITGAL), Perforin 1 (PRF1), and CD70 and studied the associations with laboratory and clinical parameters. CD4+ T cells were isolated from 35 SLE patients and 30 healthy controls. The transcript levels of ITGAL, PRF1, and CD70 were quantified by real time reverse-transcription polymerase chain reaction (RT-PCR). The SLE patients had significantly elevated transcript levels of ITGAL (18.61+/-22.17 vs. 7.33+/ 9.17, p=0.042), PRF1 (21.67+/-26.34 vs. 10.67+/-11.65, p=0.039), and CD70 (1.45+/ 1.63 vs. 0.67+/- 0.28, p=0.011). Patients with anti-microsomal and/or anti thyroglobulin antibodies showed high levels of ITGAL (33.41+/-30.14 vs. 13.58+/ 16.43, p=0.044; and 34.01+/-27.66 vs. 11.90+/-16.17, p=0.007, respectively). No association was seen either for the typical antibodies of SLE or for the disease activity. Although ITGAL, PRF1, and CD70 are overexpressed in SLE CD4+ T cells, their expression is not linked to the typical clinical and serological parameters associated with the disease. The role that ITGAL may play in autoimmune thyroiditis deserves further investigation. PMID- 24238282 TI - Imidacloprid induced histological and biochemical alterations in liver of female albino rats. AB - Imidacloprid is a neonicotinoid insecticide being used extensively for crop protection and pet flea control programmes. The effect of repeated oral administration of two doses of imidcloprid (1/10th and 1/50th of LD50 of imidacloprid) on liver of female albino rat was assessed. Histological examination of liver revealed that imidacloprid (1/10th of LD50) treatment resulted in dilations of central vein and sinusoids between hepatocytes however imidacloprid (1/50th of LD50) treatment did not induce histopathological changes in liver. Non significant decrease in alkaline phosphatase (AKP) activity was observed in imidacloprid treated rats. Liver aspartate aminotransferase level showed significant increase in higher dose of imidacloprid. Additionally, significant increases in plasma levels of aspatate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) were observed in the treated rats. The results suggest that the higher doses of imidacloprid at 1/10th of LD50 is hepatotoxic as compared to lower dose of 1/50th of LD50 of imidacloprid. PMID- 24238283 TI - Digestive enzymes activity in subsequent generations of Cameraria ohridella larvae harvested from horse chestnut trees after treatment with imidacloprid. AB - In the present study we describe the effect of chloronicotinoid pesticide (imidacloprid) on the digestive enzymes activity of the Cameraria ohridella larvae after lasting 1 year sublethal exposure to imidacloprid pesticide. Caterpillars - L4 stage (fourth instar, hyperphagic tissue-feeding phase) - were collected from chemically protected white horse chestnut trees 1 year after imidacloprid treatment, and compared with caterpillars collected from non-treated trees in a previous study. Enzymes activity of alpha-amylase, disaccharidases, glycosidases and proteases was assayed. The presence of pesticide in ingested food changed the digestive enzymes profile of caterpillars. The analysis of correlations between different digestive enzymes showed many significant correlations (P<0.05) among glycolytic activities like beta-glucosidase and alpha galactosidase activities. Statistically significant correlations for proteolytic activity were found between trypsin and chymotrypsin activity and aminopeptidase activity that occurred only in the 1st generation. PCA distinguished five primary components with eigenvalues higher than 1, from which the first two explain almost 59% of analyzed results. Surprisingly, in the pesticide treated groups significantly higher activities of sucrase and lactase in relation to control were found. In general, glycosidase (alpha-glucosidase, beta-glucosidase and beta galactosidase) activities showed a similar pattern of activity in different generations. These results contrast with those obtained with control larvae, where significant differences in activities of alpha-glucosidase, beta glucosidase and beta-galactosidase may result from the different quantity and quality food intake by subsequent generations of larvae. No inter-generation differences in total proteolytic activity were observed in treated larvae. The absolute value of total proteolytic activity was higher than that in the control group. The pesticide present in the vascular system of the horse chestnut tree significantly affected some of the digestive enzymes activities and - in consequence - also interrelationships between enzymes, what may affect the food digestion. PMID- 24238284 TI - Changes in the activity and the expression of detoxification enzymes in silkworms (Bombyx mori) after phoxim feeding. AB - Silkworm (Bombyx mori) is an economically important insect. However, non-cocoon caused by chemical insecticide poisoning has largely hindered the development of sericulture. To explore the roles of detoxification enzymes in B. mori after insecticide poisoning, we monitored the activity changes of cytochrome P450 monooxygenase, glutathione-S-transferase, and carboxylesterase in B. mori midgut and fatbody after phoxim feeding. At the same time, the expression levels of detoxification enzyme-related genes were also determined by real-time quantitative PCR. Compare to the control levels, the activity of P450 in the midgut and fatbody was increased to 1.72 and 6.72 folds; the activity of GST was no change in midgut, and in fatbody increased to 1.11 folds; the activity of carboxylesterase in the midgut was decreased to 0.69 folds, and in fatbody increased to 1.13 folds. Correspondingly, the expression levels of detoxifying enzyme genes CYP6ae22, CYP9a21, GSTo1 and Bmcce were increased to 15.99, 3.32, 1.86 and 2.30 folds in the midgut and to 3.58, 1.84, 2.14 and 4.21 folds in the fatbody after phoxim treatment. These results demonstrated the important roles of detoxification enzymes in phoxim metabolism. In addition, the detected activities of such enzymes were generally lower than those in cotton bollworms (Helicoverpa armigera), which may contribute to the high susceptibility of B. mori to insecticides. Our findings laid the foundation for further investigations of the molecular mechanisms of organophosphorus pesticide metabolism in B. mori. PMID- 24238285 TI - Effect of chronic exposure to prometryne on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.). AB - The effects of the triazine herbicide prometryne, commonly present in surface and ground waters, on oxidative stress and antioxidant status of common carp (Cyprinus carpio) were investigated. Fish were exposed to sublethal concentrations of prometryne (0.51, 8, and 80MUg/l) for 14, 30, and 60 days. Activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARSs) were assessed in brain, gill, intestine, liver, and muscle. After 14 days exposure, decreased GR activity in brain was observed for all prometryne-exposed groups compared with the controls. Changes were observed in SOD activity in brain and gill after 30 days in all exposure groups. Changes in CAT activity were observed only at the highest concentration (80MUg/l) in liver and intestine after 60 days. The observed effects on carp antioxidant systems may be a defense against oxidative damage. The study demonstrated changes in antioxidant parameters and the importance of evaluating the potential long-term risk to fish of prometryne, at environmentally realistic concentrations (0.51MUg/l). The results suggest that antioxidant responses may have potential as biomarkers for monitoring residual triazine herbicides in aquatic environments. PMID- 24238286 TI - Metabolism of quizalofop and rimsulfuron in herbicide resistant grain sorghum. AB - Studies were conducted to determine if herbicide metabolism is an additional mechanism that could explain the resistance of ACCase- and ALS-resistant grain sorghum to quizalofop and rimsulfuron, respectively. ACCase- and ALS-resistant and -susceptible genetic lines were grown under controlled conditions and treated at the 4-leaf stage with (14)C-labeled quizalofop and rimsulfuron. Plants were harvested at 3, 5, and 7d after treatments. In the ACCase metabolism experiment, resistant grain sorghum transformed 88% of quizalofop-ethyl to quizalofop while 91% of the inactive was converted to active form by the susceptible plants 3DAT. By 7DAT, all inactive quizalofop-ethyl was converted to active quizalofop. In the ALS metabolism study, two distinct metabolites were produced from rimsulfuron. Metabolism rate was similar between resistant lines (TX430R and N223R) in all harvest dates except at 7 DAT; however, more rapid metabolism were observed when resistant were compared with the susceptible genotypes (TX430S and N223S). The percentage of recovered rimsulfuron 3DAT corresponded to 80% and 83% in the resistant compared to 87% in the susceptible grain sorghum. At 5DAT, metabolism was near steady in all sorghum plants but by 7DAT, resistant genotypes metabolized 4-12% more than the susceptible sorghum. Metabolism of rimsulfuron in ALS-resistant grain sorghum is an added mechanism that could help elevate the level of rimsulfuron resistance. PMID- 24238288 TI - Transcriptional characteristics of gene expression in the midgut of domestic silkworms (Bombyx mori) exposed to phoxim. AB - Silkworm (Bombyx mori) is not only an economically important insect but also a model system for lepidoptera. As a vital organ of digestion and nutrient absorption, the midgut of insects also serves as the first physiological barrier to chemical pesticides. In this study, microarray was performed to profile the gene expression changes in the midgut of silkworms exposed to phoxim. After 24h of phoxim exposure (4.0MUg/mL), 266 genes displayed at least 2.0-fold changes in expression levels. Among them, 192 genes were up-regulated, and 74 genes were down-regulated. The most significant changes were 14.88-fold up-regulation and 23.36-fold down-regulation. According to gene ontology annotation and pathway analysis, differentially expressed genes were mainly classified into different groups based on their potential involvements in detoxification, immunne response, stress response, energy metabolism and transport. Particularly, the transcription levels of detoxification-related genes were up-regulated, such as cytochrome P450s, esterases and glutathione-S-transferase (GST), indicating increased detoxification activity in the midgut. Our study provides new insights into the molecular mechanism of pesticide metabolism in the midgut of insects, which may promote the development of highly efficient insecticides. PMID- 24238287 TI - Differences between the succinate dehydrogenase sequences of isopyrazam sensitive Zymoseptoria tritici and insensitive Fusarium graminearum strains. AB - Forty-one Zymoseptoria tritici strains isolated in Luxembourg between 2009 and 2010 were highly sensitive towards the new succinate dehydrogenase inhibitor (SDHI) isopyrazam, with concentrations inhibiting fungal growth by 50% (EC50) ranging from 0.0281 to 4.53MUM, whereas 41 Fusarium graminearum strains isolated in Europe and Northern America between 1969 and 2009 were insensitive with the average rate of inhibition converging towards 28% with increasing isopyrazam concentration. Seven isolates of both species covering the range of isopyrazam sensitivities observed in the present study were selected for the sequencing of the subunits B, C and D of the succinate dehydrogenase (sdh) gene. Predicted sdh amino acid sequences of subunits B, C and D were identical among F. graminearum strains. By comparing with fungal strains where resistance towards SDHIs was previously reported, three variations were unique to F. graminearum; B-D130N located in the iron-sulfur cluster [2Fe-2S], B-A275T located in the [3Fe-4S] cluster and an additional S at amino acid position 83-84 of sdhC, probably modifying structurally the ubiquinone binding site and therefore the biological activity of the fungicide. No variation was found among the Z. tritici strains in subunits B and D. Two variations were observed within the subunit C sequences of Z. tritici strains: C-N33T and C-N34T. The difference in EC50 values between Z. tritici strains with the NN and TT configuration was non-significant at P=0.289. Two outliers in the Z. tritici group with significantly higher EC50 values that were not related to mutations in the sdhB, sdhC, or sdhD were detected. The role of isopyrazam for the control of F. graminearum and Z. tritici in Luxembourg is discussed. PMID- 24238289 TI - Treatment with the herbicide TOPIK induces oxidative stress in cereal leaves. AB - Leaf disks as well as intact 7-day-old plants of winter wheat (Triticum aestivum L., cv. Mironovskaya 808), winter rye (Secale cereale L., cv. Estafeta Tatarstana), and maize (Zea mays L., cv. Kollektivnyi 172MV), were treated with the aryloxyphenoxypropionate class herbicide TOPIK, concentrate-emulsion (active ingredient is clodinafop-propargyl (CP), 8-800MUg/L), and the effects of short term action (up to 3h) and long-term aftereffect (up to 3days) on physiological and biochemical indices related to oxidative stress development were studied. The herbicide induced changes, predominantly increases in lipid peroxidation (LPO) intensity, superoxide anion O2(-) generation, total antioxidant activity (AOA), and catalase (CAT) and ascorbate peroxidase (APOX) activity, although the response by plants was nonlinear and depended on the herbicide concentration and duration of treatment. The highest level of generation of O2(-) was observed in the leaves of maize and winter wheat treated by 800MUg/L CP, both in the short- and long-term. As TOPIK concentration increased, so too did LPO and AOA in leaves, confirming the presence of oxidative stress in the cells of all three cereals. Antioxidant enzymes were most active in winter rye and wheat, and least active in maize indicating a protective antioxidant mechanism in the first two cereals. PMID- 24238290 TI - Inhibition of acetylcholinesterases of the pinewood nematode, Bursaphelenchus xylophilus, by phytochemicals from plant essential oils. AB - To understand the nematicidal mode of action of phytochemicals derived from plant essential oils against the pinewood nematode (Bursaphelenchus xylophilus), we evaluated 97 compounds (49 monoterpenes, 17 phenylpropenes, 16 sesquiterpenes, and 15 sulfides) for their inhibitory effects on B. xylophilus acetylcholinesterases (BxACEs). In the primary inhibition assay using B. xylophilus crude protein, more than 50% BxACE inhibition activity was observed with 3 monoterpenes, (+)-alpha-pinene, (-)-alpha-pinene, and 3-carene; 2 phenylpropenes, omicron-anisaldehyde, and coniferyl alcohol; and 1 sesquiterpene, cis-nerolidol. Other compounds showed moderate or weak inhibitory activity. The inhibitory activities against 3 recombinant BxACEs were subsequently estimated using the identified active compounds in a primary inhibition assay. (+)-alpha Pinene showed the strongest inhibition of BxACE-1 followed by 3-carene, coniferyl alcohol, (-)-alpha-pinene, o-anisaldehyde, and cis-nerolidol. The half maximal inhibitory concentration (IC50) values of (+)-alpha-pinene, 3-carene, o anisaldehyde, cis-nerolidol, and (-)-alpha-pinene against BxACE-2 were found to be 0.64, 1.41, 8.18, 8.53, 15.28, and 18.03mM, respectively. Coniferyl alcohol showed the strongest inhibition of BxACE-3 followed by (+)-alpha-pinene and cis nerolidol. PMID- 24238291 TI - Sublethal exposures of diazinon alters glucose homostasis in Wistar rats: Biochemical and molecular evidences of oxidative stress in adipose tissues. AB - Disorder of glucose homeostasis is one of the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of adipose tissue in regulating blood glucose and the role of oxidative stress in toxicity of OPs and in the continue of our previous works, in the present study we focused on tumor necrosis factor alpha (TNFalpha), glucose transporter type 4 (GLUT4), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-kappaB) in a sublethal model of toxicity by diazinon as a common OPs. Following time-course study of various doses of diazinon in impairing blood glucose, dose of 70mg/kg/day was found the optimum. Animals were treated for 4 weeks and after gavage of glucose (2g/kg), the glucose change was evaluated at time-points of 0, 30, 60, 120 and 180min to identify oral glucose tolerance test (GTT). In addition, serum insulin was measured in fasting condition. In adipose tissue, oxidative stress markers including reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and TNFalpha were evaluated. The mRNA expression of GLUT4, Nf-kappaB and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were also determined by real time reverse transcription polymerase chain reaction (RT-PCR). Diazinon at dose of 70mg/kg/day impaired GTT and diminished insulin level while augmented ROS, NADPH oxidase, and TNFalpha. The GLUT4 mRNA expression was amplified by diazinon while unlikely, the expression of Nf-kappaB gene did not change. On the basis of biochemical and molecular findings, it is concluded that diazinon impairs glucose homeostasis through oxidative stress and related proinflammatory markers in a way to result in a reduced function of insulin inside adipose tissue. Although, diazinon interfered with pancreatic influence on the adipose tissue most probably via stimulation of muscarinic receptors, current data are not sufficient to introduce adipose tissue as a target organ to OPs toxicity. Considering the potential of OPs to accumulate in adipose tissue, it seems a good candidate organ for future studies. Although, hyperglycemia was not induced by diazinon but increased AUC0 180min leads us to the point that diazinon induces kind of instability in glucose homostasis and diabetes. PMID- 24238292 TI - Inhibitory effect of esterified lactoferin and lactoferrin against tobacco mosaic virus (TMV) in tobacco seedlings. AB - The inhibitory effects of esterified lactoferrin (ELF) and lactoferrin (LF) against tobacco mosaic virus (TMV) in tobacco seedlings and the underlying mechanism were investigated. ELF and LF significantly inhibited viral infection and TMV multiplication in tobacco plants. ELF showed a higher inhibition effect against TMV than LF treatment in a dose and time-dependent way. Moreover, ELF induced a higher increase in the levels of transcription of pathogenesis-related (PR) protein genes [acidic PRs (PR-1a, PR-2, PR-3, PR-5) and basic PR-1] and defense-related enzymes [phenylalanine ammonia lyase (PAL, EC 4.3.1.5), and 5-epi aristolochene synthase (EAS, EC 2.5.1.35)] both locally and systemically, in correlation with the induction of resistance against tobacco mosaic virus. Furthermore, ELF also induced accumulation of salicylic acid, SA 2-O-beta-D glucoside and H2O2. These results suggested that ELF and LF could control TMV incidence and the mechanism might attribute to activate the expression of a number of defense genes. PMID- 24238293 TI - Screening of lethal genes for feeding RNAi by leaf disc-mediated systematic delivery of dsRNA in Tetranychus urticae. AB - To identify genes that kill Tetranychus urticae when knocked down via RNA interference (RNAi), several lethal genes were screened by the systemic delivery of dsRNA via leaf disc feeding. Four candidate genes (beta subunit of coatomer protein complex, T-COPB2; M1 metalloprotease, T-M1MP; Ribosomal protein S4, T RPS4; A subunit of V-ATPase, T-VATPase) and a control gene (EGFP) were tested for RNAi. All dsRNAs that permeated the leaf disc (ca. 15-mm diameter) were detected at 12h post-treatment, indicating that dsRNA could move through vascular tissues. To evaluate RNAi toxicity, mortalities were assessed for 120h following treatment with dsRNA. Treatment with T-COPB2, T-M1MP, T-RPS4 and T-VATPase dsRNAs caused 65.4%, 15.9%, 36.1% and 21.1% mortalities at 120h post-treatment, respectively. Reduction of all target gene transcripts following dsRNA treatment was confirmed by quantitative PCR, demonstrating that dsRNA feeding-based RNAi could indeed kill T. urticae. In summary, dsRNA delivery via leaf disc is an effective system to screen for lethal genes. Furthermore, some genes, such as T-COPB2, T-M1MP, T RPS4 and T-VATPase, can be used to establish an RNAi-based control system against T. urticae. PMID- 24238294 TI - The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection. AB - BACKGROUND: Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. RESULTS: Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml(-1)) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. CONCLUSIONS: We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism. PMID- 24238295 TI - Growth of Korean preterm infants in a family-centered tradition during early infancy: the influence of health risks, maternal employment, and the sex of infants. AB - AIM: The physical growth of mild preterm infants (<32 weeks of gestation at birth) needs to be explored in terms of bio-sociocultural factors considering the sociocultural aspects of child-care practice. METHODS: A retrospective cohort study was conducted with 238 Korean mild preterm infants from birth up to 6 months of corrected age regarding four of the biological and sociocultural factors such as health risks (at birth and discharge), maternal employment status, and the infant sex. RESULTS: There were four noteworthy findings on growth variation in Korean mild preterm infants during early infancy: (i) the secular trend of intrauterine growth; (ii) the cumulative adverse effects of four risk factors; (iii) the possible burden of maternal employment if insufficient support; and (iv) the possibility of the cultural favoritism to male infants regardless of the modern industrialized society. CONCLUSION: The study suggests that, in a modern society, while mild preterm infants could sustain typical fetal growth, the early postnatal growth may vary based on health risks and sociocultural circumstances related to child-bearing and -rearing practices surrounding them. PMID- 24238296 TI - Ocular perfusion pressure in glaucoma. AB - This review article discusses the relationship between ocular perfusion pressure and glaucoma, including its definition, factors that influence its calculation and epidemiological studies investigating the influence of ocular perfusion pressure on the prevalence, incidence and progression of glaucoma. We also list the possible mechanisms behind this association, and discuss whether it is secondary to changes in intraocular pressure, blood pressure or both. Finally, we describe the circadian variation of ocular perfusion pressure and the effects of systemic and topical medications on it. We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage. However, prospective, longitudinal studies are needed to better define the role of ocular perfusion pressure in the development and progression of glaucoma. PMID- 24238297 TI - The impact of genomic variability on gene expression in environmental Saccharomyces cerevisiae strains. AB - Environmental Saccharomyces cerevisiae strains are crucially important, as they represent the large pool from which domesticated industrial yeasts have been selected, and vineyard strains can be considered the genetic reservoir from which industrial wine strains with strong fermentative behaviour are selected. Four vineyard strains with different fermentation performances were chosen from a large collection of strains isolated from Italian vineyards. Their genomes were sequenced to identify how genetic variations influence gene expression during fermentation and to clarify the evolutionary relationship between vineyard isolates and industrial wine strains. RNA sequencing was performed on the four vineyard strains, as well as on the industrial wine yeast strain EC1118 and on the laboratory strain S288c, at two stages of fermentation. We showed that there was a large gene cluster with variable promoter regions modifying gene expression in the strains. Our results indicate that it is the evolvability of the yeast promoter regions, rather than structural variations or strain-specific genes, that is the main cause of the differences in gene expression. This promoter variability, determined by variable tandem repeats and a high number of single nucleotide polymorphisms together with 49 differentially expressed transcription factors, explained the strong phenotypic differences in the strains. PMID- 24238298 TI - Reduced beta2-glycoprotein I protects macrophages from ox-LDL-induced foam cell formation and cell apoptosis. AB - BACKGROUND: Reduced beta2-glycoprotein I (beta2-GPI) is a free thiol-containing form of beta2-GPI that displays a powerful effect in protecting endothelial cells from oxidative stress-induced cell death. The present study aims to investigate the effect of beta2-GPI or reduced beta2-GPI on ox-LDL-induced foam cell formation and on cell apoptosis and to determine the possible mechanisms. METHODS: The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining and cholesterol measurement were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as CD36, SRB1, ABCA1 and ABCG1. Western blot analysis was used to detect the protein expression of certain apoptosis-related proteins, such as caspase-9, caspase-3, p38 MAPK/p-p38 MAPK and JNK/p-JNK. RESULTS: Beta2-GPI or reduced beta2-GPI decreased ox-LDL-induced cholesterol accumulation (96.45 +/- 8.51 MUg/mg protein vs. 114.35 +/- 10.38 MUg/mg protein, p < 0.05;74.44 +/- 5.27 MUg/mg protein vs. 114.35 +/- 10.38 MUg/mg protein, p < 0.01) and cell apoptosis (30.00 +/- 5.10% vs. 38.70 +/- 7.76%, p < 0.05; 20.66 +/ 2.50% vs. 38.70 +/- 7.76%, p < 0.01), and there are significant differences between beta2-GPI and reduced beta2-GPI (p < 0.05). Reduced beta2-GPI decreased the ox-LDL-induced expression of CD36 mRNA and ABCA1 mRNA (p < 0.05), as well as CD36, cleaved caspase-9, cleaved caspase-3, p-p38 MAPK and p-JNK proteins (p < 0.05 or p < 0.01). Beta2-GPI did not significantly decrease the expression of ABCA1 mRNA and the p-p38 MAPK protein. CONCLUSIONS: Both beta2-GPI and reduced beta2-GPI inhibit ox-LDL-induced foam cell formation and cell apoptosis, and the latter exhibits a stronger inhibition effect. Both of these glycoproteins reduce the lipid intake of macrophages by downregulating CD36 as well as protein expression. Reduced beta2-GPI inhibits cell apoptosis by reducing the ox-LDL induced phosphorylation of p38 MAPK and JNK, and the amount of cleaved caspase-3 and caspase-9. Beta2-GPI does not inhibit the ox-LDL-induced phosphorylation of p38 MAPK. PMID- 24238299 TI - Brain responses to body image stimuli but not food are altered in women with bulimia nervosa. AB - BACKGROUND: Research into the neural correlates of bulimia nervosa (BN) psychopathology remains limited. METHODS: In this functional magnetic resonance imaging study, 21 BN patients and 23 healthy controls (HCs) completed two paradigms: (1) processing of visual food stimuli and (2) comparing their own appearance with that of slim women. Participants also rated food craving and anxiety levels. RESULTS: Brain activation patterns in response to food cues did not differ between women with and without BN. However, when evaluating themselves against images of slim women, BN patients engaged the insula more and the fusiform gyrus less, compared to HCs, suggesting increased self-focus among women with BN whilst comparing themselves to a 'slim ideal'. In these BN patients, exposure to food and body image stimuli increased self-reported levels of anxiety, but not craving. CONCLUSIONS: Our findings suggest that women with BN differ from HCs in the way they process body image, but not in the way they process food stimuli. PMID- 24238300 TI - The effect of temperature on the viability of human mesenchymal stem cells. AB - INTRODUCTION: Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. METHODS: The viability of human MSCs was measured after incubating them at temperatures of 38 degrees C, 48 degrees C and 58 degrees C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37 degrees C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlueTM assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett's test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlueTM) and cell viability (Trypan Blue). RESULTS: Results showed that cell metabolism was not severely affected up to 48 degrees C/150 seconds, while cells in the 58 degrees C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48 degrees C/150 seconds were compared with the control group. CONCLUSIONS: The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48 degrees C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations. PMID- 24238301 TI - Epidemiological features and risk factors associated with the spatial and temporal distribution of human brucellosis in China. AB - BACKGROUND: Human brucellosis incidence in China has been increasing dramatically since 1999. However, epidemiological features and potential factors underlying the re-emergence of the disease remain less understood. METHODS: Data on human and animal brucellosis cases at the county scale were collected for the year 2004 to 2010. Also collected were environmental and socioeconomic variables. Epidemiological features including spatial and temporal patterns of the disease were characterized, and the potential factors related to the spatial heterogeneity and the temporal trend of were analysed using Poisson regression analysis, Granger causality analysis, and autoregressive distributed lag (ADL) models, respectively. RESULTS: The epidemic showed a significantly higher spatial correlation with the number of sheep and goats than swine and cattle. The disease was most prevalent in grassland areas with elevation between 800-1,600 meters. The ADL models revealed that local epidemics were correlated with comparatively lower temperatures and less sunshine in winter and spring, with a 1-7 month lag before the epidemic peak in May. CONCLUSIONS: Our findings indicate that human brucellosis tended to occur most commonly in grasslands at moderate elevation where sheep and goats were the predominant livestock, and in years with cooler winter and spring or less sunshine. PMID- 24238302 TI - Abdominal adiposity, insulin resistance, and oxidized low-density lipoproteins in Latino adolescents. AB - Abdominal obesity and insulin resistance (IR) place youth at higher risk for premature cardiovascular disease (CVD), but the underlying mechanisms are not clear. In adults, abdominal obesity and IR contribute to the oxidation of low density lipoprotein (LDL). Whether similar mechanisms are operational in Latino adolescents is unknown. Therefore, we determined whether IR and abdominal adiposity are associated with higher oxLDL concentrations in Latino adolescents. Data from 123 Latino adolescents (16.3 +/- 2.5 years; female = 74) were used for the present analysis. Participants were assessed for waist circumference, fasting serum oxLDL, and insulin sensitivity by the whole body insulin sensitivity index. In separate linear regression models adjusting for age and sex, both waist circumference and insulin sensitivity were significant predictors of oxLDL (beta = 1.9; p = 0.002; R2 = 0.13, beta = -1.7; p = 0.006; R2 = 0.11, respectively). When insulin sensitivity and waist circumference were included in the same model, both remained independent predictors of oxLDL (beta = 1.7; p = 0.016 and, beta = 1.5; p = 0.055, respectively; R2 = 0.16). These results suggest that insulin resistance and abdominal adiposity are associated with higher levels of LDL oxidation which may be a mechanism contributing to increased CVD risk in Latino adolescents. PMID- 24238303 TI - The association between PFOA, PFOS and serum lipid levels in adolescents. AB - INTRODUCTION: Dyslipidemia in children is associated with accelerated atherosclerosis and earlier cardiovascular disease development. Environmental exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been shown to be associated with dyslipidemia in adults. However, there are few general population studies examining this association in children or adolescents. In this context, we examined the association between serum PFOA and PFOS levels and dyslipidemia in a nationally representative sample of US adolescents. METHODS: A cross-sectional study was performed on 815 participants ?18 years of age from the National Health and Nutrition Examination Survey 1999 2008. The main outcome was dyslipidemia, defined as total cholesterol >170 mg/dL, low-density lipoprotein cholesterol (LDL-C) >110 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL or triglycerides >150 mg/dL. RESULTS: We found that serum PFOA and PFOS were positively associated with high total cholesterol and LDL-C, independent of age, sex, race-ethnicity, body mass index, annual household income, physical activity and serum cotinine levels. Compared to subjects in quartile 1 (referent), the multivariable-adjusted odds ratio (95% confidence interval) for high total cholesterol among children in quartile 4 was 1.16 (1.05 2.12) for PFOA and 1.53 (1.11-1.64) for PFOS. PFOA and PFOS were not significantly associated with abnormal HDL-C and triglyceride levels. DISCUSSION: Our findings indicate that serum PFOA and PFOS are significantly associated with dyslipidemia in adolescents, even at the lower "background" exposure levels of the US general population. PMID- 24238304 TI - The fate of sulfur during rapid pyrolysis of scrap tires. AB - The fate of sulfur during rapid pyrolysis of scrap tires at temperatures from 673 to 1073K was investigated. Sulfur was predominant in the forms of thiophenic and inorganic sulfides in raw scrap tires. In the pyrolysis process, sulfur in organic forms was unstable and decomposed, leading to the sulfur release into tar and gases. At 673 and 773K, a considerable amount of sulfur was distributed in tar. Temperature increasing from 773 to 973K promoted tar decomposition and facilitated sulfur release into gases. At 1073K, the interactions between volatiles and char stimulated the formation of high-molecular-weight sulfur containing compounds. After pyrolysis, almost half of the total content of sulfur in raw scrap tires still remained in the char and was mostly in the form of sulfides. Moreover, at temperatures higher than 873K, part of sulfur in the char was immobilized in the sulfates. In the pyrolysis gases, H2S was the main sulfur containing gas. Increasing temperature stimulated the decomposition of organic polymers in scrap tires and more H2S was formed. Besides H2S, other sulfur containing gases such as CH3SH, COS and SO2 were produced during the rapid pyrolysis of scrap tires. PMID- 24238305 TI - PCDD/DF and co-planar PCB emissions from crematories in Japan. AB - Japan implemented dioxin emission guidelines for crematories in 2000, but the effects of the new guidelines have not been fully evaluated. In this study, concentrations of polychlorinated dibenzodioxins/dibenzofurans (PCDDs/DFs) and co planar polychlorinated biphenyls (co-PCBs) were measured in flue gas, fly ash, and bottom ash (mainly bone) from several crematories as a follow-up investigation. Total concentrations (O2 12% normalized) of PCDDs/DFs and co-PCBs in flue gas ranged from 4.2 to 540 ng/mN(3), and toxic equivalent concentrations ranged from 0.000053 to 11 ng-TEQ/mN(3). Based on these measurements, the average emission factor was estimated to be 1400 ng-TEQ/body. This is approximately one third the emission factor recorded in 1999. The emission factor distributions from 1999 and our study in 2007 were log-normally distributed. Emission factors were significantly lower in 2007 than in 1999, which suggests that the guidelines have been effective in reducing dioxin emissions. Meanwhile, toxic equivalent concentrations in fly ash ranged from 0.014 to 13 ng-TEQ g(-1). Higher dioxin concentrations in fly ash were observed in facilities that used a heat exchanger as a flue-gas cooling device. Because the concentrations of PCDDs/DFs and co-PCBs in flue gas were also elevated after heat exchangers during the investigation of PCDD/DF- and co-PCB-removal behaviors, secondary formation of PCDDs/DFs and co PCBs on heat exchanger surfaces unambiguously occurred. PMID- 24238306 TI - Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B. AB - BACKGROUND: Recently, we reported an information density theory and an analysis of three-parameter plus shorter scan than conventional method (3P+) for the amyloid-binding ligand [11C]Pittsburgh compound B (PIB) as an example of a non highly reversible positron emission tomography (PET) ligand. This article describes an extension of 3P + analysis to noninvasive '3P++' analysis (3P + plus use of a reference tissue for input function). METHODS: In 3P++ analysis for [11C]PIB, the cerebellum was used as a reference tissue (negligible specific binding). Fifteen healthy subjects (NC) and fifteen Alzheimer's disease (AD) patients participated. The k3 (index of receptor density) values were estimated with 40-min PET data and three-parameter reference tissue model and were compared with that in 40-min 3P + analysis as well as standard 90-min four-parameter (4P) analysis with arterial input function. Simulation studies were performed to explain k3 biases observed in 3P++ analysis. RESULTS: Good model fits of 40-min PET data were observed in both reference and target regions-of-interest (ROIs). High linear intra-subject (inter-15 ROI) correlations of k3 between 3P++ (Y-axis) and 3P + (X-axis) analyses were shown in one NC (r2 = 0.972 and slope = 0.845) and in one AD (r2 = 0.982, slope = 0.655), whereas inter-subject k3 correlations in a target region (left lateral temporal cortex) from 30 subjects (15 NC + 15 AD) were somewhat lower (r2 = 0.739 and slope = 0.461). Similar results were shown between 3P++ and 4P analyses: r2 = 0.953 for intra-subject k3 in NC, r2 = 0.907 for that in AD and r2 = 0.711 for inter-30 subject k3. Simulation studies showed that such lower inter-subject k3 correlations and significant negative k3 biases were not due to unstableness of 3P++ analysis but rather to inter-subject variation of both k2 (index of brain-to-blood transport) and k3 (not completely negligible) in the reference region. CONCLUSIONS: In [11C]PIB, the applicability of 3P++ analysis may be restricted to intra-subject comparison such as follow-up studies. The 3P++ method itself is thought to be robust and may be more applicable to other non-highly reversible PET ligands with ideal reference tissue. PMID- 24238307 TI - Over-the-scope clip for closure of persistent post-esophagectomy gastric conduit fistula. PMID- 24238308 TI - A double-blind, block-randomized, placebo-controlled trial to identify the chemical assistance effect of mesna submucosal injection for gastric endoscopic submucosal dissection. AB - BACKGROUND: Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called mesna could chemically soften connective tissues and thus facilitate endoscopic submucosal dissection (ESD). OBJECTIVE: To evaluate whether mesna injection could reduce procedural times for gastric ESD. DESIGN: Double-blind, block-randomized, controlled trial. SETTING: University hospital. PATIENTS: A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the mesna or control (saline solution) group. INTERVENTION: Traditional ESD was performed with a single bolus injection of mesna or saline solution. MAIN OUTCOME MEASUREMENTS: Time for submucosal dissection (TSD). RESULTS: En bloc resection was achieved for all lesions in the mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 +/- 13.9 [mean +/- SD] minutes for the mesna group and 24.58 +/- 24.55 [mean +/- SD] minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD (P < .05). LIMITATIONS: Single-center study. CONCLUSION: TSD was not significantly different between the mesna and control injection groups, but multivariate analysis indicated that mesna injection reduced procedural challenges associated with the submucosal dissection. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000003786.). PMID- 24238309 TI - Suck-ligate-unroof-biopsy by using a detachable 20-mm loop for the diagnosis and therapy of small subepithelial tumors (with video). AB - BACKGROUND: The diagnosis and therapy of subepithelial tumors (SETs) can be challenging. OBJECTIVE: Proof-of-concept evaluation of the suck-ligate-unroof biopsy (SLUB) technique for small (<2 cm), non-pedunculated SETs. DESIGN: Pilot feasibility study. SETTING: Tertiary-care referral center. PATIENTS: Twenty-three patients (median age 60 years) meeting the inclusion criteria after preliminary EUS. INTERVENTION: SET ligation was performed with a detachable 20-mm loop deployed through an 18-mm diameter, soft, oblique, transparent, cap attachment. The SLUB technique comprised (1) suction to draw the SET into the cap; (2) ligation below the SET, confirmation by repeat EUS; (3) unroofing of the overlying mucosa with a needle-knife; and (4) biopsy specimens taken from the exposed tumor. MAIN OUTCOME MEASUREMENTS: Technical success, histology and/or immunohistochemistry yield, adverse events, completeness of resection. RESULTS: SLUB was attempted on 24 SETs and was technically successful in all. Location was the stomach (n = 19), small bowel (n = 1), colon (n = 2), and rectum (n = 2). Median size by EUS was 10 mm (range 6-15 mm). Biopsy specimens provided an immunohistologic diagnosis in all cases: GI stromal tumor (n = 5), leiomyoma (n = 8), carcinoid tumor (n = 5), Vanek's tumor (n = 2), granuloma (n =1), and pancreatic heterotopia (n = 3). Follow-up endoscopy and EUS in 13 patients showed well-healed scars with no residual tumor, including all 9 patients with premalignant neoplastic lesions. The only adverse event was self-limited pain in 2 patients. LIMITATIONS: Single center, single operator, small sample size. CONCLUSIONS: Loop ligation of small, non-pedunculated SETs is feasible by using a cap attachment for suction. Unroofing after ligation is safe and provides sufficient tissue for immunohistochemistry. Ligation combined with unroofing appears to lead to complete ablation by ischemia and tumor enucleation. PMID- 24238310 TI - Dental Implant Macro-Design Features Can Impact the Dynamics of Osseointegration. AB - PURPOSE: The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. MATERIALS AND METHODS: Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Molndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with alpha = 0.05 was performed. RESULTS: An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter thread gaps (p < .05). Concomitantly, the Aadva macro-design negatively affected the amount of bone in direct contact with the implant for this specific implant part (p < .05), and resulted in an overall impaired implant osseointegration at the initial healing stage (total implant length; 1-month healing; p < .05). CONCLUSION: Although the Aadva implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment. PMID- 24238311 TI - The diagnosis of acute mesenteric ischemia: A systematic review and meta analysis. AB - OBJECTIVES: Acute mesenteric ischemia is an infrequent cause of abdominal pain in emergency department (ED) patients; however, mortality for this condition is high. Rapid diagnosis and surgery are key to survival, but presenting signs are often vague or variable, and there is no pathognomonic laboratory screening test. A systematic review and meta-analysis of the available literature was performed to determine diagnostic test characteristics of patient symptoms, objective signs, laboratory studies, and diagnostic modalities to help rule in or out the diagnosis of acute mesenteric ischemia in the ED. METHODS: In concordance with published guidelines for systematic reviews, the medical literature was searched for relevant articles. The Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) for systematic reviews was used to evaluate the overall quality of the trials included. Summary estimates of diagnostic accuracy were computed by using a random-effects model to combine studies. Those studies without data to fully complete a two-by-two table were not included in the meta analysis portion of the project. RESULTS: The literature search identified 1,149 potentially relevant studies, of which 23 were included in the final analysis. The quality of the diagnostic studies was highly variable. A total of 1,970 patients were included in the combined population of all included studies. The prevalence of acute mesenteric ischemia ranged from 8% to 60%. There was a pooled sensitivity for l-lactate of 86% (95% confidence interval [CI] = 73% to 94%) and a pooled specificity of 44% (95% CI = 32% to 55%). There was a pooled sensitivity for D-dimer of 96% (95% CI = 89% to 99%) and a pooled specificity of 40% (95% CI = 33% to 47%). For computed tomography (CT), we found a pooled sensitivity of 94% (95% CI = 90% to 97%) and specificity of 95% (95% CI = 93% to 97%). The positive likelihood ratio (+LR) for a positive CT was 17.5 (95% CI = 5.99 to 51.29), and the negative likelihood ratio (-LR) was 0.09 (95% CI = 0.05 to 0.17). The pooled operative mortality rate for mesenteric ischemia was 47% (95% CI = 40% to 54%). Given these findings, the test threshold of 2.1% (below this pretest probability, do not test further) and a treatment threshold of 74% (above this pretest probability, proceed to surgical management) were calculated. CONCLUSIONS: The quality of the overall literature base for mesenteric ischemia is varied. Signs, symptoms, and laboratory testing are insufficiently diagnostic for the condition. Only CT angiography had adequate accuracy to establish the diagnosis of acute mesenteric ischemia in lieu of laparotomy. PMID- 24238313 TI - The effect of medical trainees on pediatric emergency department flow: a discrete event simulation modeling study. AB - BACKGROUND: Providing patient care and medical education are both important missions of teaching hospital emergency departments (EDs). With medical school enrollment rising, and ED crowding becoming an increasing prevalent issue, it is important for both pediatric EDs (PEDs) and general EDs to find a balance between these two potentially competing goals. OBJECTIVES: The objective was to determine how the number of trainees in a PED affects patient wait time, total ED length of stay (LOS), and rates of patients leaving without being seen (LWBS) for PED patients overall and stratified by acuity level as defined by the Pediatric Canadian Triage and Acuity Scale (CTAS) using discrete event simulation (DES) modeling. METHODS: A DES model of an urban tertiary care PED, which receives approximately 40,000 visits annually, was created and validated. Thirteen different trainee schedules, which ranged from averaging zero to six trainees per shift, were input into the DES model and the outcome measures were determined using the combined output of five model iterations. RESULTS: An increase in LOS of approximately 7 minutes was noted to be associated with each additional trainee per attending emergency physician working in the PED. The relationship between the number of trainees and wait time varied with patients' level of acuity and with the degree of PED utilization. Patient wait time decreased as the number of trainees increased for low-acuity visits and when the PED was not operating at full capacity. With rising numbers of trainees, the PED LWBS rate decreased in the whole department and in the CTAS 4 and 5 patient groups, but it rose in patients triaged CTAS 3 or higher. A rising numbers of trainees was not associated with any change to flow outcomes for CTAS 1 patients. CONCLUSIONS: The results of this study demonstrate that trainees in PEDs have an impact mainly on patient LOS and that the effect on wait time differs between patients presenting with varying degrees of acuity. These findings will assist PEDs in finding a balance between providing high-quality medical education and timely patient care. PMID- 24238312 TI - Patient demographic and health factors associated with frequent use of emergency medical services in a midsized city. AB - OBJECTIVES: To optimize health care utilization, health outcomes, and costs, research is needed to improve an understanding of frequent users of emergency health services. Frequent use of emergency services is associated with high costs of health care and may be indicative of challenges accessing, or poor outcomes of, health care. Patient demographics and health factors related to frequent use of the emergency medical services (EMS) system of a midsized city were identified. Study findings will aid in the development of targeted interventions to improve population health. METHODS: The authors reviewed 9-1-1 call dispatch data and Baltimore City Fire Department (BCFD) EMS records from 2008 through 2010. Frequent use was defined as six or more EMS incidents in the 23-month period. Analyses used census data to compare demographics of EMS users to their population distribution and examined differences in demographics and health problems of frequent EMS users compared to nonfrequent users. RESULTS: Frequent EMS users (n = 1,969) had a range of six to 199 EMS incidents (mean = 11.2) during the observation period, and although they accounted for only 1.5% of EMS users, they were involved in 12.0% of incidents. Frequent users, compared to nonfrequent users and to the population, were more likely to be male, African American, and 45 years of age or older. Of frequent users, the modal age group was 45 to 54 years, accounting for 29.7% of frequent users, which represented twice this age group's population distribution. Furthermore, this age group had the greatest overrepresentation of males (63.0% of frequent users) and was the peak age group for incidents related to substance abuse (28.0% of frequent users' incidents in this age group). Frequent users, compared to nonfrequent users, had lower levels of incidents related to trauma (5.1% vs. 16.7%) and higher levels of medical incidents (94.8% vs. 82.9%). As proportions of EMS incidents among frequent versus nonfrequent users, respiratory, mental health, and seizure related incidents were highest in the youngest age groups; substance abuse related incidents were highest in those middle-aged (35 to 44 and 45 to 54 years). Of health problems, behavioral health (mental health or substance use) contributed most to frequent EMS use (23.4% of frequent users' incidents). Across all incidents, 65.8% of frequent users had indications of behavioral health problems, representing 6.6-fold higher odds than nonfrequent users (22.5%). Frequent compared to nonfrequent users also had higher levels of select chronic conditions (diabetes, 39.9% vs. 14.6%; asthma, 40.9% vs. 13.4%; and HIV, 9.1% vs. 2.4%), with unadjusted odds almost four to seven times higher. CONCLUSIONS: The study findings revealed the major role of chronic somatic and behavioral health problems in frequent EMS use and that rates of frequent use were highest among those middle-aged, African American, and male. These results suggest the need for coordination of EMS with community-based, integrated medical and behavioral health services to improve access and use of preventive services, with implications for health outcomes and costs. This study demonstrates the value of EMS patient data in identifying at-risk populations and informing novel, targeted approaches to public health interventions. PMID- 24238314 TI - Comparison of the "real-life" diagnostic value of two recently published electrocardiogram methods for the differential diagnosis of wide QRS complex tachycardias. AB - OBJECTIVES: The diagnostic values of the aVR lead or "Vereckei algorithm," and the lead II R-wave peak time (RWPT) criterion, recently devised for the differential diagnosis of wide QRS complex tachycardias (WCTs), were compared. METHODS: A total of 212 WCTs (142 ventricular tachycardias [VTs], 62 supraventricular tachycardias [SVT], and eight preexcitation SVTs) from 145 patients with proven electrophysiologic diagnoses were retrospectively analyzed by seven examiners blinded to the electrophysiologic diagnoses. RESULTS: The overall test accuracy of the Vereckei algorithm was superior to that of the RWPT criterion (84.3% vs. 79.6%; p = 0.0003). The sensitivity of the Vereckei algorithm for VT diagnosis was greater than that of RWPT criterion (92.4% vs. 79.1%; p < 0.0001). The negative predictive value (NPV) for the Vereckei algorithm was also greater (77.8%; 95% confidence interval [CI] = 73.6% to 82.1%) than that of the RWPT criterion (61.6%; 95% CI = 57.6% to 65.6%). The specificity of the Vereckei algorithm was lower than that of the RWPT criterion (64.7% vs. 80.9%; p < 0.0001). The positive predictive value (PPV) was also lower for the Vereckei algorithm (86.4%; 95% CI = 84.4% to 88.4%) than for the RWPT criterion (90.9%; 95% CI = 89.1% to 92.8%). Incorrect diagnoses made by the Vereckei algorithm were mainly due to misdiagnosis of SVT as VT (65.7% of cases), and those made by the RWPT criterion were due to the more dangerous misdiagnosis of VT as SVT (72.5% of cases). CONCLUSIONS: The Vereckei algorithm was superior in overall test accuracy, sensitivity, and NPV for VT diagnosis and inferior in specificity and PPV to the RWPT criterion. All of these parameters were lower in "real life" than those reported by the original authors for each of the particular electrocardiographic methods. PMID- 24238315 TI - A cost-effectiveness analysis comparing a clinical decision rule versus usual care to risk stratify children for intraabdominal injury after blunt torso trauma. AB - OBJECTIVES: Recently a clinical decision rule (CDR) to identify children at very low risk for intraabdominal injury needing acute intervention (IAI) following blunt torso trauma was developed. Potential benefits of a CDR include more appropriate abdominal computed tomography (CT) use and decreased hospital costs. The objective of this study was to compare the cost-effectiveness of implementing the CDR compared to usual care for the evaluation of children with blunt torso trauma. The hypothesis was that compared to usual care, implementation of the CDR would result in lower CT use and hospital costs. METHODS: A cost-effectiveness decision analytic model was constructed comparing the costs and outcomes of implementation of the CDR to usual care in the evaluation of children with blunt torso trauma. Probabilities from a multicenter cohort study of children with blunt torso trauma were derived; estimated costs were based on those at the study coordinating site. Outcome measures included missed IAI, number of abdominal CT scans, total costs, and incremental cost-effectiveness ratios. Sensitivity analyses varying imputed probabilities, costs, and scenarios were conducted. RESULTS: Using a hypothetical cohort of 1,000 children with blunt torso trauma, the base case model projected that the implementation of the CDR would result in 0.50 additional missed IAIs, a total cost savings of $54,527, and 104 fewer abdominal CT scans compared to usual care. The usual care strategy would cost $108,110 to prevent missing one additional IAI. Findings were robust under multiple sensitivity analyses. CONCLUSIONS: Compared to usual care, implementation of the CDR in the evaluation of children with blunt torso trauma would reduce hospital costs and abdominal CT imaging, with a slight increase in the risk of missed intraabdominal IAI. PMID- 24238316 TI - Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis. AB - OBJECTIVES: The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). METHODS: A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. RESULTS: In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. CONCLUSIONS: To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. PMID- 24238317 TI - Value of point-of-care ketones in assessing dehydration and acidosis in children with gastroenteritis. AB - OBJECTIVES: Children with gastroenteritis often develop dehydration with metabolic acidosis. Serum ketones are frequently elevated in this population. The goal was to determine the relationship between initial serum ketone concentration and both the degree of dehydration and the magnitude of acidosis. METHODS: This was a secondary analysis of a prospective trial of crystalloid administration for rapid rehydration. Children 6 months to 6 years of age with gastroenteritis and dehydration were enrolled. A point-of-care serum ketone (beta-hydroxybutyrate) concentration was obtained at the time of study enrollment. The relationship between initial serum ketone concentration and a prospectively assigned and previously validated clinical dehydration score, and serum bicarbonate concentration, was analyzed. RESULTS: A total of 188 patients were enrolled. The median serum ketone concentration was elevated at 3.1 mmol/L (interquartile range [IQR] = 1.2 to 4.6 mmol/L), and the median dehydration score was consistent with moderate dehydration. A significant positive relationship was found between serum ketone concentration and the clinical dehydration score (Spearman's rho = 0.22, p = 0.003). Patients with moderate dehydration had a higher median serum ketone concentration than those with mild dehydration (3.6 mmol/L vs. 1.4 mmol/L, p = 0.007). Additionally, the serum ketone concentration was inversely correlated with serum bicarbonate concentration (rho = -0.26, p < 0.001). CONCLUSIONS: Children with gastroenteritis and dehydration have elevated serum ketone concentrations that correlate with both degree of dehydration and magnitude of metabolic acidosis. Point-of-care serum ketone measurement may be a useful tool to inform management decisions at the point of triage or in the initial evaluation of children with gastroenteritis and dehydration. PMID- 24238318 TI - Use of butterfly needles to draw blood is independently associated with marked reduction in hemolysis compared to intravenous catheter. AB - OBJECTIVES: Hemolysis of blood samples drawn in the emergency department (ED) is a common problem that can interfere with timely diagnosis and appropriate treatment. The objective of this study was to identify the smallest number of remediable factors that independently increases the risk of hemolysis to design an effective strategy to address this issue. METHODS: This was a prospective, observational, cross-sectional study of blood specimens obtained by ED staff in an urban, academic, adult ED in a tertiary care center. The staff member who drew the specimen recorded data on a standardized data collection instrument about device (intravenous [IV] catheter or butterfly needle), needle size, anatomic site, fullness of collection tube, tourniquet time, and difficulty of venipuncture. Specimens were sent to the laboratory by a vacuum-powered tube system. A standard automated process that measures free hemoglobin was used to identify hemolysis. A multivariable logistic regression and a tabular analysis stratified by device were performed. Ninety-five percent confidence intervals (CIs) were calculated around the odds ratios (ORs) and around the difference between hemolysis rates. RESULTS: Data were collected on 5,118 blood specimens. There were 4,513 specimens with complete data on all characteristics of the blood draw included in the analyses. The overall hemolysis rate was 12.5% (95% CI = 11.6% to 13.5%), 14.6% in blood drawn from IV catheters and 2.7% from butterfly needles (difference = 11.9%; 95% CI = 10.2% to 13.4%). Device was the strongest independent predictor of hemolysis (OR = 7.7; 95% CI = 4.9 to 12.0). In specimens drawn by IV catheter, hemolysis was significantly higher when blood was drawn from locations other than the antecubital fossa, with small-gauge catheters, collection tubes <= half full, tourniquet time >= 1 minute, and difficult venipuncture. In contrast, none of these factors was associated with hemolysis when blood was drawn by butterfly needle. CONCLUSIONS: The device used to collect blood was the strongest independent predictor of hemolysis in blood samples drawn in the ED in this study. This finding suggests that the most effective strategy to reduce the rate of hemolysis in the ED is to use butterfly needles for phlebotomy rather than IV catheters. PMID- 24238319 TI - Generalizability of a simple approach for predicting hospital admission from an emergency department. AB - OBJECTIVES: The objective was to test the generalizability, across a range of hospital sizes and demographics, of a previously developed method for predicting and aggregating, in real time, the probabilities that emergency department (ED) patients will be admitted to a hospital inpatient unit. METHODS: Logistic regression models were developed that estimate inpatient admission probabilities of each patient upon entering an ED. The models were based on retrospective development (n = 4,000 to 5,000 ED visits) and validation (n = 1,000 to 2,000 ED visits) data sets from four heterogeneous hospitals. Model performance was evaluated using retrospective test data sets (n = 1,000 to 2,000 ED visits). For one hospital the developed model also was applied prospectively to a test data set (n = 910 ED visits) coded by triage nurses in real time, to compare results to those from the retrospective single investigator-coded test data set. RESULTS: The prediction models for each hospital performed reasonably well and typically involved just a few simple-to-collect variables, which differed for each hospital. Areas under receiver operating characteristic curves (AUC) ranged from 0.80 to 0.89, R(2) correlation coefficients between predicted and actual daily admissions ranged from 0.58 to 0.90, and Hosmer-Lemeshow goodness-of-fit statistics of model accuracy had p > 0.01 with one exception. Data coded prospectively by triage nurses produced comparable results. CONCLUSIONS: The accuracy of regression models to predict ED patient admission likelihood was shown to be generalizable across hospitals of different sizes, populations, and administrative structures. Each hospital used a unique combination of predictive factors that may reflect these differences. This approach performed equally well when hospital staff coded patient data in real time versus the research team retrospectively. PMID- 24238321 TI - Decreasing length of stay in the emergency department with a split emergency severity index 3 patient flow model. AB - OBJECTIVES: There has been a steady increase in emergency department (ED) patient volume and wait times. The desire to maintain or decrease costs while improving throughput requires novel approaches to patient flow. The break-out session "Interventions to Improve the Timeliness of Emergency Care" at the June 2011 Academic Emergency Medicine consensus conference "Interventions to Assure Quality in the Crowded Emergency Department" posed the challenge for more research of the split Emergency Severity Index (ESI) 3 patient flow model. A split ESI 3 patient flow model divides high-variability ESI 3 patients from low-variability ESI 3 patients. The study objective was to determine the effect of implementing a split ESI 3 flow model has on patient length of stay (LOS) for discharged patients. METHODS: This was a retrospective chart review at an urban academic ED seeing over 70,000 adult patients a year. Cases consisted of adults who presented from 9 a.m. to 11 p.m. from June 1, 2011, to December 31, 2011, and were discharged. Controls were patients who presented on the same times and days, but in 2010. Visit descriptors included age, race, sex, ESI score, and first diagnosis. The first diagnosis was coded based on methods used by the Agency for Healthcare Research and Quality to codify International Classification of Diseases, ninth version, into disease groups. Linear models compared log-transformed LOS for cases and controls. A front-end ED redesign involved creating guidelines to split ESI 3 patients into low and high variability, a hybrid sort/triage registered nurse, an intake area consisting of an internal results waiting room, and a treatment area for patients after initial assessment. The previous low-acuity area (ESI 4s and 5s) began to see low-variability ESI 3 patients as well. This was done without additional beds. The intake area was staffed with an attending emergency physician (EP), a physician assistant (PA), three nurses, two medical technicians, and a scribe. RESULTS: There was a 5.9% decrease, from 2.58 to 2.43 hours, in the geometric mean of LOS for discharged patients from 2010 to 2011 (95% confidence interval CI = 4.5% to 7.2%; 2010, n = 20,215; 2011, n = 20,653). Abdominal pain was the most common diagnostic grouping (2010, n = 2,484; 2011, n = 2,464) with a reduction in LOS of 12.9%, from 4.37 to 3.8 hours (95% CI = 10.3% to 15.3%). CONCLUSIONS: A split ESI 3 patient flow model improves door-to discharge LOS in the ED. PMID- 24238320 TI - Developing emergency department-based education about emergency contraception: adolescent preferences. AB - OBJECTIVES: The objective was to identify adolescent preferences for emergency department (ED)-based education about emergency contraception. METHODS: This was a cross-sectional computerized survey, using adaptive conjoint analysis (ACA). Patients were eligible if they were females ages 14 through 19 years old and were seeking care in one of two urban EDs. Patients were excluded if they were too ill to participate in the survey or if they were non-English speaking. Participants completed a computerized survey that used ACA, a technique that can be used to assess patients' relative preferences for services. ACA uses the individual's answers to update and refine questions through trade-off comparisons, so that each respondent answers a customized set of questions. The survey assessed preferences for the following attributes of emergency contraception education: who should deliver the education, if anyone (e.g., nurse, doctor); how the education should be delivered (e.g., by a person or via video); how often the education should be offered if patients were to frequent the ED (e.g., every time or only when asking for it); length (e.g., 5 minutes, 10 minutes); and chief complaint that would trigger the education (e.g., headache or stomach pain). RESULTS: A total of 223 patients were enrolled (37.2% at Hospital 1 and 62.8% at Hospital 2). The mean (+/-SD) age of the participants was 16.1 (+/-1.3) years. Just over half (55%) reported a history of sexual activity; 8% reported a history of pregnancy. Overall, the participants preferred education that was delivered by a person, specifically a doctor or nurse. They preferred a slightly longer education session and preferred education directed at patients seeking care in the ED for complaints potentially related to sexual activity. CONCLUSIONS: Adolescents have specific preferences for how education about emergency contraception would best serve their needs. This information can inform clinicians as they work to improve adolescents' knowledge about pregnancy prevention and emergency contraception in particular. PMID- 24238322 TI - Understanding the direction of bias in studies of diagnostic test accuracy. AB - Ordering and interpreting diagnostic tests is a critical part of emergency medicine (EM). In evaluating a study of diagnostic test accuracy, emergency physicians (EPs) need to recognize whether the study uses case-control or cross sectional sampling and account for common biases. The authors group biases in studies of test accuracy into five categories: incorporation bias, partial verification bias, differential verification bias, imperfect gold standard bias, and spectrum bias. Other named biases are either equivalent to these biases or subtypes within these broader categories. The authors go beyond identifying a bias and predict the direction of its effect on sensitivity and specificity, providing numerical examples from published test accuracy studies. Understanding the direction of a bias may permit useful inferences from even a flawed study of test accuracy. PMID- 24238323 TI - Reply to comment on 'Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades' E. Feldtkeller, A. Zeller, M. Rudwaleit. PMID- 24238324 TI - Retinal layers measurements in healthy eyes and in eyes receiving silicone oil based endotamponade. AB - PURPOSE: To characterize the concordance/symmetry of each retinal layers in individuals without macular pathology and to further characterize the localization of inner retinal thinning in eyes receiving silicone oil-based endotamponade. METHODS: Retinal layers of one hundred eyes of 50 individuals without macular pathology were imaged using spectral domain optical coherence tomography (SD-OCT) and manually segmented using ImageJ software (developed by Wayne Rasband, NIH, Bethesda, MD, USA). In the second part of the study, retrospective analysis of 3028 cases of pars plana vitrectomy in University Eye Hospital Cologne, Germany, was conducted, retrieving nine patients with silicone oil-based endotamponade with no macular condition interfering retinal layers measurements. These patients had retinal detachment not involving the macula due to various conditions. In these patients, retinal layer segmentation was performed and compared with the fellow eye. RESULTS: There is a moderate-to-high concordance for all retinal layers between the right and the left eye of the same individual. In eyes receiving silicone oil-based endotamponade, the inner retinal layers become subsequently thinner. Ganglion cell and inner plexiform layers contribute most to this thinning, that is, 0.537 +/- 0.096 mm(3) compared with 0.742 +/- 0.117 mm(3) ; p = 0.006. Outer retinal layers were not affected by silicone oil-based endotamponade (p = 0.439 for the differences of calculated outer retinal layers). CONCLUSION: Ganglion cell and inner retinal layers become subsequently thinner after the use of silicone oil-based endotamponade. This study advocates the use of spectral domain optical coherence tomography for patient management with silicone oil endotamponade to early detect subsequent retinal thinning. PMID- 24238325 TI - Comparison of malignant skin tumor thickness and relative depth of invasion estimates from preoperative MR-microscopy and pathological evaluation. AB - BACKGROUND: Tumor thickness and relative depth of invasion are prognostic parameters considered when developing treatment plans for malignant skin tumors. Although conventional magnetic resonance (MR) imaging techniques cannot identify small tumors, use of microscopy coils considerably improves spatial resolution. Some studies have shown that this technique is efficacious in preoperative assessment of relative depth of invasion; however, its ability to provide accurate measurements of tumor thickness remains unconfirmed. OBJECTIVE: The purpose of this pilot study was to evaluate the usefulness of preoperative MR microscopy in determining tumor thickness and relative depth of invasion of malignant skin tumors. METHODS AND MATERIALS: Magnetic resonance images of malignant skin tumors in seven female patients (six with basal cell carcinoma and one with malignant melanoma) were obtained using a 1.5 T system and a 47-mm or 23 mm microscopy coil. Tumors were then excised, fixed, dehydrated, embedded, and stained with hematoxylin and eosin. We then compared MR-microscopy and pathology values for thickness and relative depth of invasion of each tumor. RESULTS: Both techniques produced similar measurements of tumor thickness and relative depth of invasion. CONCLUSIONS: MR-microscopy is very useful for accurate preoperative estimation of not only relative depth of invasion, but also thickness of malignant skin tumors. PMID- 24238326 TI - Assessment of esophageal dysfunction and symptoms during and after a standardized test meal: development and clinical validation of a new methodology utilizing high-resolution manometry. AB - BACKGROUND: In the absence of major dysmotility, esophageal manometry with water swallows rarely explains the causes of esophageal symptoms and disease. This methodology development study assessed esophageal function and symptoms during a test meal in patients with reflux symptoms and asymptomatic controls. The impact of this approach on manometric diagnosis and clinical outcome was reviewed. METHODS: 18 patients with reflux symptoms and 10 healthy volunteers underwent high resolution manometry (HRM) with 5 mL water swallows, 200 mL water drink, and standardized solid test meal followed by 10 min postprandial observation. The number of symptoms associated with esophageal dysfunction (SAD) divided by total symptoms (dysfunction symptom index [D-SI]) was calculated. Ambulatory reflux pH monitoring was performed. Final diagnosis and clinical outcome were documented at 2 years. KEY RESULTS: Meal intake took longer in patients than controls (552 vs 339 s) and this was associated with a higher number of ineffective swallows in this group (51% vs 28%; p < 0.001). No swallowing problems occurred with water swallows but 12/18 (66%) patients had SAD during either the meal or postprandial observations with D-SI >50% in 9/12 (75%). Compared with water swallows, manometric classification was altered in 12/18 (67%) and clinical diagnosis was altered in 7/18 (39%) patients due to test meal observations. CONCLUSIONS & INFERENCES: A novel methodology for the detection of symptomatic dysmotility during a test meal and postprandial observation is presented. This technique increased the diagnostic yield of esophageal dysfunction in patients presenting with reflux symptoms. Long-term follow-up indicated that these observations can guide effective clinical management. PMID- 24238327 TI - Novel antilisterial bacteriocin licheniocin 50.2 from Bacillus licheniformis VPS50.2 isolated from soil sample. AB - AIM: To isolate and characterize bacteriocin, licheniocin 50.2, from soil bacteria identified as Bacillus licheniformis. METHODS AND RESULTS: The strain B. licheniformis VPS50.2 was identified as bacteriocin producer, effective against Gram-positive bacteria, including Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA) and beta-haemolytic streptococci. The start of bacteriocin production coincides with the beginning of sporulation. Ammonium sulfate precipitation, chloroform extraction and ultrafiltration were used for bacteriocin purification. MALDI TOF/TOF mass spectrometry of purified sample detected the protein with molecular mass of 3253.209 Da. N-terminal sequencing recognized first 15 amino acids with the sequence: W E E Y N I I X Q L G N K G Q. We named the newly characterized bacteriocin as subclass II.3 bacteriocin, licheniocin 50.2. The bacteriocin activity was insensitive to lysozyme and proteinase K, heat stable after incubation at 100 degrees C for 30 min and over wide range of pH (2-12). MICs of crude bacteriocin extract were determined for L. monocytogenes and MRSA. Time-kill study showed that licheniocin had bactericidal effect to L. monocytogenes. CONCLUSION: A novel, thermostable, pH-tolerant bacteriocin active against Gram-positive bacteria was isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: Attributes of new, stable licheniocin 50.2 make it a promising agent for application as biopreservative in food industry. PMID- 24238328 TI - Skin disorders in overweight and obese patients and their relationship with insulin. AB - INTRODUCTION: The prevalence of obesity has increased worldwide in recent years. Some authors have described skin conditions associated with obesity, but there is little evidence on the association between insulin levels and such disorders. OBJECTIVE: To describe the skin disorders present in overweight and obese patients and analyze their association with insulin levels. MATERIAL AND METHODS: The study included nondiabetic male and female patients over 6 years of age who were seen at our hospital between January and April 2011. All the patients were evaluated by a dermatologist, who performed a physical examination, including anthropometry, and reviewed their medical history and medication record; fasting blood glucose and insulin were also measured. The patients were grouped according to degree of overweight or obesity and the data were compared using analysis of variance or the chi(2) test depending on the type of variable. The independence of the associations was assessed using regression analysis. RESULTS: In total, 109 patients (95 adults and 13 children, 83.5% female) were studied. The mean (SD) age was 38 (14) years and the mean body mass index was 39.6+/-8 kg/m(2). The skin conditions observed were acanthosis nigricans (AN) (in 97% of patients), skin tags (77%), keratosis pilaris (42%), and plantar hyperkeratosis (38%). Statistically significant associations were found between degree of obesity and AN (P=.003), skin tags (P=.001), and plantar hyperkeratosis. Number of skin tags, AN neck severity score, and AN distribution were significantly and independently associated with insulin levels. CONCLUSIONS: AN and skin tags should be considered clinical markers of hyperinsulinemia in nondiabetic, obese patients. PMID- 24238329 TI - Clinical characteristics of patients with cutaneous melanoma according to variants in the melanocortin 1 receptor gene. AB - INTRODUCTION: Patients with cutaneous melanoma who are carriers of polymorphisms in the melanocortin 1 receptor gene (MC1R) have distinctive clinical characteristics. The objective of this study was to determine the clinical characteristics associated with differing degrees of functional impairment of the melanocortin 1 receptor, as determined by the number and type (R and r) of MC1R polymorphisms. MATERIAL AND METHODS: In total, 1044 consecutive patients with melanoma diagnosed in our hospital after January 2000 were selected from the melanoma database. These patients were divided into 3 groups according to a score based on nonsynonymous MC1R polymorphisms. The frequencies of epidemiologic, phenotypic, and histologic variables and personal and family history of cancer were compared. RESULTS: Patients with a score of 3 or more were more likely to develop melanoma before the age of 50 years (odds ratio [OR]=1.47), have a tumor on the head or neck (OR=3.04), have a history of basal cell carcinoma or cutaneous squamous cell carcinoma (OR=1.70), have atypical nevi (OR=1.74), and have nevi associated with the melanoma (OR=1.87). CONCLUSIONS: The use of a scoring system for MC1R polymorphisms allowed us to identify associations between the degree of functional impairment of the melanogenesis pathway and the clinical characteristics of the patients and melanoma presentation. PMID- 24238330 TI - Pachydermodactyly in a patient with generalized anxiety disorder and tics. PMID- 24238331 TI - Hypopigmented macules in a young man. Hypopigmented mycoses fungoides. PMID- 24238332 TI - Re-irradiation of spinal column metastases by IMRT: impact of setup errors on the dose distribution. AB - BACKGROUND: This study investigates the impact of an automated image guided patient setup correction on the dose distribution for ten patients with in-field IMRT re-irradiation of vertebral metastases. METHODS: 10 patients with spinal column metastases who had previously been treated with 3D-conformal radiotherapy (3D-CRT) were simulated to have an in-field recurrence. IMRT plans were generated for treatment of the vertebrae sparing the spinal cord. The dose distributions were compared for a patient setup based on skin marks only and a Cone Beam CT (CBCT) based setup with translational and rotational couch corrections using an automatic robotic image guided couch top (Elekta - HexaPODTM IGuide(r) - system). The biological equivalent dose (BED) was calculated to evaluate and rank the effects of the automatic setup correction for the dose distribution of CTV and spinal cord. RESULTS: The mean absolute value (+/- standard deviation) over all patients and fractions of the translational error is 6.1 mm (+/-4 mm) and 2.7 degrees (+/-1.1 mm) for the rotational error. The dose coverage of the 95% isodose for the CTV is considerable decreased for the uncorrected table setup. This is associated with an increasing of the spinal cord dose above the tolerance dose. CONCLUSIONS: An automatic image guided table correction ensures the delivery of accurate dose distribution and reduces the risk of radiation induced myelopathy. PMID- 24238333 TI - Anaerobic degradation of homocyclic aromatic compounds via arylcarboxyl-coenzyme A esters: organisms, strategies and key enzymes. AB - Next to carbohydrates, aromatic compounds are the second most abundant class of natural organic molecules in living organic matter but also make up a significant proportion of fossil carbon sources. Only microorganisms are capable of fully mineralizing aromatic compounds. While aerobic microbes use well-studied oxygenases for the activation and cleavage of aromatic rings, anaerobic bacteria follow completely different strategies to initiate catabolism. The key enzymes related to aromatic compound degradation in anaerobic bacteria are comprised of metal- and/or flavin-containing cofactors, of which many use unprecedented radical mechanisms for C-H bond cleavage or dearomatization. Over the past decade, the increasing number of completed genomes has helped to reveal a large variety of anaerobic degradation pathways in Proteobacteria, Gram-positive microbes and in one archaeon. This review aims to update our understanding of the occurrence of aromatic degradation capabilities in anaerobic microorganisms and serves to highlight characteristic enzymatic reactions involved in (i) the anoxic oxidation of alkyl side chains attached to aromatic rings, (ii) the carboxylation of aromatic rings and (iii) the reductive dearomatization of central arylcarboxyl coenzyme A intermediates. Depending on the redox potential of the electron acceptors used and the metabolic efficiency of the cell, different strategies may be employed for identical overall reactions. PMID- 24238334 TI - IRF4 provides rations for cytotoxic CD8(+) T cell soldiers. AB - The transcription factor IRF4 is known to be essential for differentiation of effector CD4(+) T cell subsets. In this issue, Yao et al. (2013) identify IRF4 as a regulator of checkpoints in the final steps and maintenance of CD8(+) T cell effector differentiation. PMID- 24238335 TI - Septic shock: on the importance of being tolerant. AB - A study by Figueiredo et al. (2013) in this issue of Immunity demonstrates that administration of anthracyclines induces autophagy in vivo and has a powerful protective effect in a mouse model of sepsis. PMID- 24238336 TI - The bipolar role of miR-466l in inflammation. AB - Special proresolving mediators (SPMs) limit the intensity of inflammation; however, their regulation is poorly understood. In this issue of Immunity, Li et al. (2013) describe bipolar roles for miR-466l in the promotion of inflammation and the induction of SPMs. PMID- 24238337 TI - A sting in the tale of TH2 immunity. AB - Allergies are widely considered misguided Th2 cell responses. In this issue, Palm et al. (2013) and Marichal et al. (2013) show that mice mount anti-venom Th2 cell responses that share components of the "allergic" response but confer protection. PMID- 24238339 TI - The polycomb protein Ezh2 regulates differentiation and plasticity of CD4(+) T helper type 1 and type 2 cells. AB - After antigen encounter by CD4(+) T cells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial trimethylation at lysine 27 of histone 3 (H3K27me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN gamma and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-gamma expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. In vivo, loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells. This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4(+) T cells. PMID- 24238338 TI - The spleen in local and systemic regulation of immunity. AB - The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity. PMID- 24238340 TI - The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner. AB - The peptidoglycan sensor Nod2 and the autophagy protein ATG16L1 have been linked to Crohn's disease (CD). Although Nod2 and the related sensor, Nod1, direct ATG16L1 to initiate anti-bacterial autophagy, whether ATG16L1 affects Nod-driven inflammation has not been examined. Here, we uncover an unanticipated autophagy independent role for ATG16L1 in negatively regulating Nod-driven inflammatory responses. Knockdown of ATG16L1 expression, but not that of ATG5 or ATG9a, specifically enhanced Nod-driven cytokine production. In addition, autophagy incompetent truncated forms of ATG16L1 regulated Nod-driven cytokine responses. Mechanistically, we demonstrated that ATG16L1 interfered with poly-ubiquitination of the Rip2 adaptor and recruitment of Rip2 into large signaling complexes. The CD-associated allele of ATG16L1 was impaired in its ability to regulate Nod driven inflammatory responses. Overall, these results suggest that ATG16L1 is critical for Nod-dependent regulation of cytokine responses and that disruption of this Nod1- or Nod2-ATG16L1 signaling axis could contribute to the chronic inflammation associated with CD. PMID- 24238341 TI - Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators. AB - The magnitude and duration of acute inflammation are controlled by active resolution programs involving specialized proresolving mediators (SPMs; resolvins and maresins) and microRNAs (miRNAs). Here, we report that miR-466l was temporally regulated in murine exudate-infiltrating leukocytes. Neutrophil miR 466l overexpression in vivo promoted initiation of inflammation that anteceded macrophage expression of this miRNA, which accelerated resolution when overexpressed. In macrophages, miR-466l overexpression increased prostanoids and SPMs (e.g., resolvin D1 [RvD1] and RvD5), which enhanced resolution. RvD1, RvD2, maresin 1 (MaR1), and apoptotic neutrophils reduced miR-466l expression within human macrophages, a feedback regulation that most likely prepares for homeostasis. miR-466l was upregulated in peripheral blood of sepsis patients, and its increase correlated with nonsurvival from sepsis. SPMs and miR-466l regulated transcription factors activator protein 1 and nuclear factor kappaB1 in miRNA biogenesis. These results demonstrate pivotal roles for SPMs and miR-466l in dynamic leukocyte plasticity during resolution of acute inflammatory responses. PMID- 24238342 TI - Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus. AB - Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV. PMID- 24238344 TI - Predictors of quality of life in patients with heart failure. AB - AIM: To understand quality of life (QOL) and the effects of sociodemographics, disease severity, physical symptoms (dyspnea and fatigue), and depression on QOL of heart failure (HF) patients in Taiwan. METHODS: Adult HF patients with history of cerebral vascular accident, myocardial infarction within the previous 6 months, major diseases, concurrent cancers, and coexisting terminal diseases, cognitive impairments, or residence in institutions, were excluded in this study. Quality of life, physical symptoms, and depression were measured by the Minnesota Living with Heart Failure Questionnaire, Pulmonary Function Status and Dyspnea Questionnaire, and Brief Symptom Inventory depression subscale, respectively. Hierarchical regression analyses were used to examine the correlations of demographics, disease severity, physical symptoms, and depression with QOL in HF patients. RESULTS: One hundred and thirty-three HF patients (64.2 +/- 12.7 years, 78.2% male, 36.1% NYHA III/IV) were recruited in the study. In the final regression model, age, duration of HF, physical symptoms, and depression had a significant impact on global QOL, ultimately accounting for 37.6% of the variance of QOL. CONCLUSION: Age, duration of HF, physical symptoms, and depression are important predictors of QOL in HF patients. Interventions targeting physical symptoms and depression are expected to improve QOL of HF patients. PMID- 24238343 TI - Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. AB - Stable Foxp3 expression is crucial for regulatory T (Treg) cell function. We observed that antigen-driven activation and inflammation in the CNS promoted Foxp3 instability selectively in the autoreactive Treg cells that expressed high amounts of Foxp3 before experimental autoimmune encephalitis induction. Treg cells with a demethylated Treg-cell-specific demethylated region in the Foxp3 locus downregulated Foxp3 transcription in the inflamed CNS during the induction phase of the response. Stable Foxp3 expression returned at the population level with the resolution of inflammation or was rescued by IL-2-anti-IL-2 complex treatment during the antigen priming phase. Thus, a subset of fully committed self-antigen-specific Treg cells lost Foxp3 expression during an inflammatory autoimmune response and might be involved in inadequate control of autoimmunity. These results have important implications for Treg cell therapies and give insights into the dynamics of the Treg cell network during autoreactive CD4(+) T cell effector responses in vivo. PMID- 24238345 TI - Robotic kidney transplantation with intraoperative regional hypothermia. AB - OBJECTIVE: To describe a novel and reproducible technique of robotic kidney transplantation (RKT) that requires no repositioning, and permits intraoperative regional hypothermia. PATIENTS AND METHODS: A GelPOINTTM (Applied Medical, Santa Ranchero, CA, USA) access port was used for delivery of ice-slush and introduction of the graft kidney. The new RKT technique using ice-slush has been performed in 39 patients. RESULTS: At a mean follow-up of 3 months all of the grafts functioned. There was a marked reduction in pain and analgesic requirement compared with patients undergoing open KT, with a propensity towards quicker graft recovery and lower complication rate. CONCLUSION: RKT has been shown to be safe and feasible in patients undergoing living-donor related KT. A prospective trial is underway to assess outcomes definitively. PMID- 24238346 TI - Efficacy and cost-effectiveness of a web-based intervention with mobile phone support to treat depressive symptoms in adults with diabetes mellitus type 1 and type 2: design of a randomised controlled trial. AB - BACKGROUND: A diagnosis of diabetes mellitus types 1 or 2 doubles the odds of a comorbid depressive disorder. The combined diseases have a wide range of adverse outcomes, such as a lower quality of life, poorer diabetes outcomes and increased healthcare utilisation. Diabetes patients with depression can be treated effectively with psychotherapy, but access to psychological care is limited. In this study we will examine the efficacy and cost-effectiveness of a newly developed web-based intervention (GET.ON Mood Enhancer Diabetes) for people with diabetes and comorbid depressive symptoms. METHODS/DESIGN: A two-arm randomised controlled trial will be conducted. Adults with diabetes (type 1 or type 2) with increased depression scores (> 22 on the German version of the Center for Epidemiological Studies Depression Scale (CES-D)) will be included. Eligible participants will be recruited through advertisement in diabetes patient journals and via a large-scale German health insurance company. The participants will be randomly assigned to either a 6-week minimally guided web-based self-help program or an online psychoeducation program on depression. The study will include 260 participants, which will enable us to detect a statistically significant difference with a group effect size of d = 0.35 at a power of 80% and a significance level of p = 0.05. The primary outcome measure will be the level of depression as assessed by the CES-D. The secondary outcome measures will be: diabetes-specific emotional distress, glycaemic control, self-management behaviour and the participants' satisfaction with the intervention. Online self assessments will be collected at baseline and after a 2 months period, with additional follow-up measurements 6 and 12 months after randomisation. The data will be analysed on an intention-to-treat basis and per protocol. In addition, we will conduct an economic evaluation from a societal perspective. DISCUSSION: If this intervention is shown to be cost-effective, it has considerable potential for implementing psychological care for large numbers of people with diabetes and comorbid depression in routine practice and improve health outcomes. TRIAL REGISTRATION: German Clinical Trial Register (DRKS): DRKS00004748. PMID- 24238347 TI - Analysis of fluorescent reporters indicates heterogeneity in glucose uptake and utilization in clonal bacterial populations. AB - BACKGROUND: In this study, we aimed at investigating heterogeneity in the expression of metabolic genes in clonal populations of Escherichia coli growing on glucose as the sole carbon source. Different metabolic phenotypes can arise in these clonal populations through variation in the expression of glucose transporters and metabolic enzymes. First, we focused on the glucose transporters PtsG and MglBAC to analyze the diversity of glucose uptake strategies. Second, we analyzed phenotypic variation in the expression of genes involved in gluconeogenesis and acetate scavenging (as acetate is formed and excreted during bacterial growth on glucose), which can reveal, for instance, phenotypic subpopulations that cross-feed through the exchange of acetate. In these experiments, E. coli MG1655 strains containing different transcriptional GFP reporters were grown in chemostats and reporter expression was measured with flow cytometry. RESULTS: Our results suggest heterogeneous expression of metabolic genes in bacterial clonal populations grown in glucose environments. The two glucose transport systems exhibited different level of heterogeneity. The majority of the bacterial cells expressed the reporters for both glucose transporters MglBAC and PtsG and a small fraction of cells only expressed the reporter for Mgl. At a low dilution rate, signals from transcriptional reporters for acetyl-CoA synthetase Acs and phosphoenolpyruvate carboxykinase Pck indicated that almost all cells expressed the genes that are part of acetate utilization and the gluconeogenesis pathway, respectively. Possible co-existence of two phenotypic subpopulations differing in acs expression occurred at the threshold of the switch to overflow metabolism. The overflow metabolism results in the production of acetate and has been previously reported to occur at intermediate dilution rates in chemostats with high concentration of glucose in the feed. CONCLUSIONS: Analysis of the heterogeneous expression of reporters for genes involved in glucose and acetate metabolism raises new question whether different metabolic phenotypes are expressed in clonal populations growing in continuous cultures fed on glucose as the initially sole carbon source. PMID- 24238349 TI - Presenteeism and pain: psychosocial and demographic correlates of employment and disability. PMID- 24238348 TI - Evaluation of prediction models for the staging of prostate cancer. AB - BACKGROUND: There are dilemmas associated with the diagnosis and prognosis of prostate cancer which has lead to over diagnosis and over treatment. Prediction tools have been developed to assist the treatment of the disease. METHODS: A retrospective review was performed of the Irish Prostate Cancer Research Consortium database and 603 patients were used in the study. Statistical models based on routinely used clinical variables were built using logistic regression, random forests and k nearest neighbours to predict prostate cancer stage. The predictive ability of the models was examined using discrimination metrics, calibration curves and clinical relevance, explored using decision curve analysis. The N = 603 patients were then applied to the 2007 Partin table to compare the predictions from the current gold standard in staging prediction to the models developed in this study. RESULTS: 30% of the study cohort had non organ-confined disease. The model built using logistic regression illustrated the highest discrimination metrics (AUC = 0.622, Sens = 0.647, Spec = 0.601), best calibration and the most clinical relevance based on decision curve analysis. This model also achieved higher discrimination than the 2007 Partin table (ECE AUC = 0.572 & 0.509 for T1c and T2a respectively). However, even the best statistical model does not accurately predict prostate cancer stage. CONCLUSIONS: This study has illustrated the inability of the current clinical variables and the 2007 Partin table to accurately predict prostate cancer stage. New biomarker features are urgently required to address the problem clinician's face in identifying the most appropriate treatment for their patients. This paper also demonstrated a concise methodological approach to evaluate novel features or prediction models. PMID- 24238350 TI - New policing role for pharmacists undermines partnership with prescribers. PMID- 24238351 TI - Upscheduling of hydrocodone: convenience and access vs patient safety measures. PMID- 24238352 TI - Better late than never: time to up-schedule hydrocodone combination products. PMID- 24238353 TI - The downside of upscheduling. PMID- 24238354 TI - Among disparate views, scales tipped by the ethics of system integrity. PMID- 24238355 TI - PTSD and pain: exploring the impact of posttraumatic cognitions in veterans seeking treatment for PTSD. AB - OBJECTIVE: Previous research has demonstrated a significant relationship between posttraumatic stress disorder (PTSD) and pain. While several models attempt to explain this relationship, significant questions remain regarding factors that may play a role in this interaction. The purpose of this study was to determine whether posttraumatic cognitions mediate the relationship between PTSD and pain. DESIGN: The sample comprised 136 veterans who presented to the VA Ann Arbor Health Care System seeking evaluation and treatment in the PTSD clinic. Participants completed the Clinician-Administered PTSD Scale, the Posttraumatic Cognitions Inventory, and Brief Pain Inventory-Short Form, along with other assessments as part of their evaluation. RESULTS: This study showed that the majority of patients (86.8%) reported some problems with pain. Further, the findings indicate that there is a significant relationship between PTSD severity and pain severity. Posttraumatic cognitions were not related to the level of pain experienced, but they were related to pain interference in this population. CONCLUSIONS: In particular, negative cognitions regarding the self were associated with the level of pain-related interference, and partially mediated the relationship between PTSD and pain. The clinical implications of these findings are discussed. PMID- 24238356 TI - Features of urate deposition in patients with gouty arthritis of the foot using dual-energy computed tomography. AB - OBJECTIVES: To investigate features of urate deposition in gout and the association between these features and attacks of gouty arthritis using dual energy computed tomography (CT). METHODS: Dual-energy CT scans of both feet were performed in 80 consecutive patients with gout and 22 with asymptomatic hyperuricemia. RESULTS: Overall, 333 areas of urate deposition were found in patients with gout. The most commonly affected sites were the first metatarsophalangeal joint (MPJ; 57/333), the distal area of the first toe (59/333) and the calcaneal bone (61/333). For episodes of the first MPJ arthritis, urate deposits in the flexor pollicis longus muscle tendon (P = 0.02), as well as solitary and punctate depositions (P = 0.03 and 0.01, respectively) were positively related to the acute attacks. For episodes of arthritis around the ankle, deposits in the area, including the talus and inferior tibia, were associated with attacks of arthritis at the ankle (P = 0.02); additionally, deposits in the flexor tendon adjacent to the inferior tibia (P < 0.01) and a punctiform conformation were significantly associated with attacks of arthritis (P = 0.02). Logistic regression analysis showed that deposits around the first MPJ (OR = 3.38, 95% CI: 1.32, 8.17) or around the talus and inferior tibia (OR = 2.83, 95% CI: 1.11, 7.15) would increase the risk of an attack of arthritis. CONCLUSIONS: Dual-energy CT imaging can be used to detect and analyze the features of urate deposition in patients with gout. Specific features of the deposits appeared to be associated with acute attacks of gouty arthritis. PMID- 24238358 TI - The association and predictive value analysis of metabolic syndrome combined with resting heart rate on cardiovascular autonomic neuropathy in the general Chinese population. AB - BACKGROUND: The purpose of this study was to explore the extent of associations of cardiovascular autonomic neuropathy (CAN) with metabolic syndrome (MetS) and resting heart reate (HR), and to evaluate the predictive value of MetS combined with HR on CAN in a large sample derived from a Chinese population. MATERIALS AND METHODS: We conducted a large-scale, population-based, cross-sectional study to explore the relationships of CAN with MetS and resting HR. This study included 2092 participants aged 30-80 years, and a total of 387 subjects were diagnosed with CAN in our dataset. The associations of CAN with MetS and resting HR were assessed by a multivariate logistic regression (MLR) analysis (using subjects without CAN as a reference group) after controlling for potential confounding factors. The predictive performance of resting HR and MetS was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: A tendency toward increased CAN prevalence with increasing resting HR was reported (p for trend < 0.001). MLR analysis showed that MetS and resting HR were very significantly and independently associated with CAN (beta = 0.495 for MetS and beta = 0.952 for HR, P < 0.001 for both). Resting HR alone and combined with MetS (MetS-HR) strongly predicted CAN (AUC = 0.719, P < 0.001 for resting HR and AUC = 0.735, P < 0.001 for MetS-HR). CONCLUSION: Our findings signify that MetS and resting HR were very significantly and independently associated with CAN in the general Chinese population. Resting HR and MetS-HR both have a high value in predicting CAN in the general population. PMID- 24238357 TI - Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China. AB - BACKGROUND: The clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates. METHODS: Forty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-beta-lactamase (MBL) was determined using the MBL Etest. RESULTS: Forty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (>= 7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T -> C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A -> C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 MUg/ml, and that of AML ranged from 40 to 320 MUg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL. CONCLUSIONS: CC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL. PMID- 24238360 TI - Control design for the SISO system with the unknown order and the unknown relative degree. AB - For the uncertain system whose order, relative degree and parameters are unknown in the control design, new research is still in need on the parameter tuning and close-loop stability. During the last 10 years, much progress is made in the application and theory research of the active disturbance rejection control (ADRC) for the uncertain system. In this study, the necessary and sufficient conditions are established for building the ADRC for the minimum-phase system and the open-loop stable system when the plant parameters, orders and relative degrees are unknown, the corresponding ideal dynamics are analyzed, and the theoretical results are verified by the simulations. Considering the wide application and the long history of the PID/PI controller, a method is given to design ADRC quickly based on the existing (generalized or conventional) PID/PI controller. A plenty of simulations are made to illustrate this PID/PI-based design method and the corresponding close-loop performances. The simulation examples include the minimum/nonminimum-phase plants, the stable/integrating plants, the high/low-order plant, and the plants with time delays. Such plants are from a wider scope than the theoretical result, and representative of many kinds of the industrial processes. That leads to a new way to simplify the ADRC design via absorbing the engineering experience in designing the PID/PI controller. PMID- 24238359 TI - Locomotor and postural development of wild chimpanzees. AB - Chimpanzees are our closest living relatives and their positional repertoire likely includes elements shared with our common ancestor. Currently, limitations exist in our ability to correlate locomotor anatomy with behavioral function in the wild. Here we provide a detailed description of developmental changes in chimpanzee locomotion and posture. Fieldwork was conducted on wild chimpanzees at Ngogo, Kibale National Park, Uganda. The large size of the Ngogo chimpanzee community permitted cross-sectional analysis of locomotor and postural changes across many individuals. Chimpanzee positional behavior proceeds developmentally through a number of distinct stages, each characterized by its own loading regime. Infants principally used their upper limbs while moving; the loading environment changed to more hindlimb dominated locomotion as infants aged. Infants displayed more diversity in their forms of positional behavior than members of any other age-sex class, engaging in behaviors not habitually exhibited by adults. While the most common locomotor mode for infants was torso orthograde suspensory locomotion, a large shift toward quadrupedal locomotion during infancy occurred at three years of age, when rates of this behavior increased. Overall, the most dramatic transition in positional behavior occurred during juvenility (at approximately five years), with the advent of complete independent locomotion. Juveniles decreased the amount of time they spent clinging and in torso-orthograde suspensory locomotion and increased their time spent sitting and walking and running quadrupedally compared with younger individuals. Juvenility marked the age at which quadrupedal walking became the most frequent locomotor behavior, but quadrupedal walking did not encompass the majority of locomotor time until individuals reached adolescence. Relative to all younger individuals, adolescent chimpanzees (10-13 years) experienced a further increase in the amount of time they walked quadrupedally. Locomotor behavior did not reach adult form until adolescence, closer to the time of epiphyseal fusion than previously thought. These findings provide new data to make predictions about how behavioral transitions influence skeletal change. PMID- 24238361 TI - A hybrid disturbance rejection control solution for variable valve timing system of gasoline engines. AB - A novel solution for electro-hydraulic variable valve timing (VVT) system of gasoline engines is proposed, based on the concept of active disturbance rejection control (ADRC). Disturbances, such as oil pressure and engine speed variations, are all estimated and mitigated in real-time. A feed-forward controller was added to enhance the performance of the system based on a simple and static first principle model, forming a hybrid disturbance rejection control (HDRC) strategy. HDRC was validated by experimentation and compared with an existing manually tuned proportional-integral (PI) controller. The results show that HDRC provided a faster response and better tolerance of engine speed and oil pressure variations. PMID- 24238362 TI - Dopamine signaling in food addiction: role of dopamine D2 receptors. AB - Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA signaling in mesolimbic neurotransmission are widely believed to modify reward-related behaviors and are therefore closely associated with drug addiction. Recent evidence now suggests that as with drug addiction, obesity with compulsive eating behaviors involves reward circuitry of the brain, particularly the circuitry involving dopaminergic neural substrates. Increasing amounts of data from human imaging studies, together with genetic analysis, have demonstrated that obese people and drug addicts tend to show altered expression of DA D2 receptors in specific brain areas, and that similar brain areas are activated by food-related and drug related cues. This review focuses on the functions of the DA system, with specific focus on the physiological interpretation and the role of DA D2 receptor signaling in food addiction. PMID- 24238364 TI - Effect of pulsed light on structural and physiological properties of Listeria innocua and Escherichia coli. AB - AIMS: The application of broad-spectrum intense light pulses is an innovative nonthermal technology for the decontamination of packaging materials, liquids or foodstuffs. The objective of this study was the fundamental investigation of the cellular impact of a pulsed light treatment on Listeria innocua and Escherichia coli. METHODS AND RESULTS: Flow cytometry in combination with different fluorescent stains, conventional plate count technique and a viability assay were applied to investigate the effects of a pulsed light treatment on the physiological properties of L. innocua and E. coli. The results showed that loss of cultivability occurred at considerably lower fluences than the shutdown of cellular functions such as the depolarization of cell membranes, the loss of metabolic, esterase and pump activities or the occurrence of membrane damage. Therefore, a considerable proportion of cells appeared to have entered the viable but nonculturable (VBNC) state after the pulsed light treatment. A high percentage of L. innocua was able to maintain certain cellular vitality functions after storage overnight, whereas a further decrease in vitality was observed in case of E. coli. The loss of culturability was on the other hand directly accompanied by the formation of reactive oxygen species (ROS) and DNA damages, which were assessed by the ROS-sensitive probe DCFH-DA and RAPD-PCR, respectively. CONCLUSIONS: A significant discrepancy between conventional plate counts and different viability staining parameters was observed, which shows that a pulsed light treatment does not cause an immediate shutdown of vitality functions even when the number of colony-forming units already decreased for more than 6 log10 sample(-1) . Oxidative stress with concomitant damage to the DNA molecule showed to be directly responsible for the loss of cultivability due to pulsed light rather than a direct rupture of cell membranes or inactivation of intracellular enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented results suggest an UV light-induced photochemical rather than a photothermal or photophysical inactivation of bacterial cells by pulsed light under the applied experimental conditions. Flow cytometry in combination with different viability stains proved to be a suitable technique to gain deeper insight into the cellular response of bacteria to inactivation processes like a pulsed light treatment. PMID- 24238363 TI - CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis. AB - Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed. PMID- 24238365 TI - High levels of genetic diversity in Nosema ceranae within Apis mellifera colonies. AB - Nosema ceranae is a widespread honeybee parasite, considered to be one of the pathogens involved in the colony losses phenomenon. To date, little is known about its intraspecific genetic variability. The few studies on N. ceranae variation have focused on the subunits of ribosomal DNA, which are not ideal for this purpose and have limited resolution. Here we characterized three single copy loci (Actin, Hsp70 and RPB1) in three N. ceranae isolates from Hungary and Hawaii. Our results provide evidence of unexpectedly high levels of intraspecific polymorphism, the coexistence of a wide variety of haplotypes within each bee colony, and the occurrence of genetic recombination in RPB1. Most haplotypes are not shared across isolates and derive from a few frequent haplotypes by a reduced number of singletons (mutations that appear usually just once in the sample), which suggest that they have a fairly recent origin. Overall, our data indicate that this pathogen has experienced a recent population expansion. The presence of multiple haplotypes within individual isolates could be explained by the existence of different strains of N. ceranae infecting honeybee colonies in the field which complicates, and must not be overlooked, further analysis of host parasite interactions. PMID- 24238366 TI - Measurement of skin and target dose in post-mastectomy radiotherapy using 4 and 6 MV photon beams. AB - BACKGROUND: For patients with high risk breast cancer and mastectomy, radiotherapy is the treatment of choice to improve survival and local control. Target dose is mainly limited due to skin reactions. The feasibility of using 4 MV beams for chest wall treatment was studied and compared to standard 6 MV bolus radiotherapy. METHODS: Post-mastectomy IMRT was planned on an Alderson-phantom using 4 and 6 MV photon beams without/with a 0.5 cm thick bolus. Dose was measured using TLDs placed at 8 locations in 1 and 3 mm depth to represent skin and superficial target dose, respectively. RESULTS: 4 MV and 6 MV beams with bolus perform equally regarding target coverage. The minimum and mean superficial target dose for the 6 MV and 4 MV were 93.0% and 94.7%, and 93.1% and 94.4%, respectively. Regarding skin dose the 4 MV photon beam was advantageous. The minimum and mean skin dose for the 6 MV and 4 MV was 76.7% and 81.6%, and 69.4% and 72.9%, respectively. The TPS was able to predict dose in the build-up region with a precision of around 5%. CONCLUSIONS: The use of 4 MV photon beams are a good alternative for treating the thoracic wall without the need to place a bolus on the patient. The main limitation of 4 MV beams is the limited dose rate. PMID- 24238367 TI - Sex-for-Crack exchanges: associations with risky sexual and drug use niches in an urban Canadian city. AB - BACKGROUND: While crack cocaine has been associated with elevated sexual risks and transmission of HIV/STIs, particularly in the context of street-based sex work, few empirical studies have examined correlates of direct sex-for-crack exchanges. This study longitudinally examined the correlates of sex-for-crack exchanges and associated effects on sexual risk outcomes among street-based female sex workers (SW) who use drugs in Vancouver, Canada. METHODS: Data were drawn from a prospective cohort of street-based SWs (2006-2008), restricted to those who smoke crack cocaine. Multivariable generalized estimating equations (GEE) were employed to examine the correlates of exchanging sex for crack. A confounding model using GEE quasi-Poisson regression modeled the independent effect of exchanging sex for crack on number of clients/week. RESULTS: Of 206 SWs, 101 (49%) reported sex-for-crack exchanges over 18 months of follow-up. In multivariable GEE analyses, sharing a crack pipe with a client (aOR = 1.98; 95%CI: 1.27-3.08) and smoking crack in a group of strangers (e.g., in an alley or crackhouse) (aOR = 1.70; 95% CI: 1.13-2.58) were independently correlated with sex-for-crack exchanges. In our confounding model, exchanging sex for crack (aIRR = 1.34; 95% CI: 1.07-1.69) remained significantly associated with servicing a greater number (>10) of clients/week. CONCLUSIONS: These findings reveal elevated sexual- and drug- risk patterns among those who exchange sex for crack. The physical and social environment featured prominently in our results as a driver of sex-for-crack exchanges, highlighting the need for gender-sensitive multilevel approaches to harm reduction, STI and HIV prevention that address SWs' environment, individual level factors, and the interplay between them. PMID- 24238368 TI - Stretch-dependent smooth muscle differentiation in the portal vein-role of actin polymerization, calcium signaling, and microRNAs. AB - The mechanical forces acting on SMC in the vascular wall are known to regulate processes such as vascular remodeling and contractile differentiation. However, investigations to elucidate the underlying mechanisms of mechanotransduction in smooth muscle have been hampered by technical limitations associated with mechanical studies on pressurized small arteries, due primarily to the small amount of available tissue. The murine portal vein is a relatively large vessel showing myogenic tone that in many respects recapitulates the properties of small resistance vessels. Studies on stretched portal veins to elucidate mechanisms of mechanotransduction in the vascular wall have shown that stretch-sensitive regulation of contractile differentiation is mediated via Rho-activation and actin polymerization, while stretch-induced growth is regulated by the MAPK pathway. In this review, we have summarized findings on mechanotransduction in the portal vein with focus on stretch-induced contractile differentiation and the role of calcium, actin polymerization and miRNAs in this response. PMID- 24238369 TI - Bimanual examination of the retrieved specimen and regional hypothermia during robot-assisted radical prostatectomy: a novel technique for reducing positive surgical margin and achieving pelvic cooling. AB - OBJECTIVE: To describe a novel method of achieving pelvic hypothermia during robot-assisted radical prostatectomy (RARP) and a modification of technique allowing immediate organ retrieval for intraoperative examination and targeted frozen-section biopsies. PATIENTS AND METHODS: Intracorporeal cooling and extraction (ICE) consists of a modification of the standard RARP technique with the use of the GelPOINTTM (Applied Medical, Rancho Santa Margarita, CA, USA), a hand access platform, which allows for delivery of ice-slush and rapid specimen extraction without compromising pneumoperitoneum. RESULTS: The ICE technique reproducibly achieves a temperature of 15 degrees C in the pelvic cavity with no obvious body temperature change. Adopting this technique during RARP, there was an absolute risk reduction by 26.6% in positive surgical margin rate in patients with pT3a disease when compared with similar patients undergoing conventional RARP (P = 0.04). CONCLUSIONS: The ICE technique eliminates the potential handicap of decreased tactile sensation for oncological margins, especially in the high risk patients. This technique allows the surgeon to immediately examine the surgical specimen after resection, and with the aid of frozen-section pathology determine if further resection is required. A prospective trial is underway in our centre to evaluate the effects of this novel technique on postoperative outcomes. PMID- 24238370 TI - Chronic migraine in women is associated with insulin resistance: a cross sectional study. AB - BACKGROUND AND PURPOSE: Migraine is a common neurological disorder. It can be divided into episodic migraine (EM) and chronic migraine (CM), based on headache frequency. Some studies have shown that insulin sensitivity is impaired in migraine; moreover, hypertension, diabetes and obesity are common in patients with CM. The aim of this study was to assess serum glucose, insulin levels and insulin resistance (IR) in a sample of episodic migraineurs, chronic migraineurs and non-pain healthy controls. METHODS: Eighty-three women with EM, 83 with CM and 83 healthy controls were recruited. Headache was diagnosed according to the latest International Classification of Headache Disorders 2 criteria. Waist circumference, body mass index (BMI) and blood pressure were measured. Checked metabolic parameters included fasting glucose, the 2 h 75 g oral glucose tolerance test (2 h OGTT), serum HbA1c, blood lipid profile, C-reactive protein and prolactin. The homeostasis model assessment formula was used to calculate IR. RESULTS: A significant prevalence of IR in CM was observed (P = 0.002). No significant associations were found with fasting glycaemia, the 2 h OGTT, HbA1c, blood lipid profile, C-reactive protein, prolactin and waist circumference. Obesity (BMI >30 kg/m(2)) was associated with an increased risk of CM [odds ratio (OR) 2.4]. When the outcome of interest was the association between IR and obesity, the OR was significantly increased compared with IR alone (OR = 13.2). CONCLUSION: This may suggest that CM is associated with IR status, particularly when it is in partnership with obesity. PMID- 24238372 TI - Dermoscopy-assisted sclerotherapy for spider leg veins. PMID- 24238371 TI - Use of withdrawal (coitus interruptus) for both pregnancy and HIV prevention among young adults in Rakai, Uganda. AB - INTRODUCTION: Although understudied in the context of AIDS, use of withdrawal (coitus interruptus) with or in place of other prevention methods affects exposure to both pregnancy and human immunodeficiency virus (HIV). AIM: We used mixed methods to assess use of withdrawal among 15-24-year-olds in a rural Ugandan setting with considerable HIV prevalence. METHODS: We measured withdrawal reporting among (i) sexually active 15-24-year-olds enrolled in a quantitative community survey (n = 6,722) and (ii) in-depth qualitative interview participants systematically selected from the latest round of the community survey (N = 60). Respondents were asked about family planning and HIV prevention practices, including a direct question about withdrawal in the in-depth interviews. MAIN OUTCOME MEASURES: The main outcome measures were reports of current use of withdrawal on the quantitative survey (general question about family planning methods) and reports of current or recent use withdrawal in qualitative interviews (specific question about withdrawal). Qualitative interviews also probed for factors associated with withdrawal use. RESULTS: Although less than 1% of quantitative survey participants spontaneously named withdrawal as their current family planning method, 48% of qualitative interview respondents reported current or lifetime use of withdrawal. Withdrawal was often used as a pleasurable alternative to condoms, when condoms were not available, and/or as a "placeholder" method before obtaining injectable contraception. A few respondents described using withdrawal to reduce HIV risk. CONCLUSION: Qualitative findings revealed widespread withdrawal use among young adults in Rakai, mainly as a condom alternative. Thus, withdrawal may shape exposure to both pregnancy and HIV. Future behavioral surveys should assess withdrawal practices directly--and separately from other contraceptives and HIV prevention methods. Further clinical research should further document withdrawal's association with HIV risk. PMID- 24238373 TI - Introduction to special issue on tumor ablation. PMID- 24238375 TI - How to set up a successful tumor ablation practice. AB - Tumor ablation services have increased in prevalence across the country and can now be found in modern health care systems of all sizes. These services have become an integral part of the coordinated multidisciplinary approach to patient care that must take place at any oncologic center of excellence. However, building a reputable tumor ablation practice at an institutional level can be a very difficult task as there are many financial, political, and material considerations that must be addressed during the early phases of operation to ensure its success. This article discusses each of these considerations in turn and provides insight into ways to overcome the inherent challenges faced when bringing all of the necessary elements together to create a thriving tumor ablation practice at an institutional level. PMID- 24238374 TI - Tumor ablation: common modalities and general practices. AB - Tumor ablation is a minimally invasive technique that is commonly used in the treatment of tumors of the liver, kidney, bone, and lung. During tumor ablation, thermal energy is used to heat or cool tissue to cytotoxic levels (less than -40 degrees C or more than 60 degrees C). An additional technique is being developed that targets the permeability of the cell membrane and is ostensibly nonthermal. Within the classification of tumor ablation, there are several modalities used worldwide: radiofrequency, microwave, laser, high-intensity focused ultrasound, cryoablation, and irreversible electroporation. Each technique, although similar in purpose, has specific and optimal indications. This review serves to discuss general principles and technique, reviews each modality, and discusses modality selection. PMID- 24238376 TI - Preparation for percutaneous ablation procedures. AB - Percutaneous tumor ablation is now commonly used to treat a wide range of focal tumors. Patients eligible for ablation often have complex medical problems that preclude them from receiving other treatments. The interventional radiologist needs to perform a careful clinical evaluation of each patient before the procedure to determine which patients are suitable candidates for treatment and to identify patients who may be at a higher risk for complications. The clinical consultation also provides an opportunity to prepare the patient for the ablation and to appropriately plan the procedure. In this article, we discuss key components of the consultation and concepts regarding patient evaluation and preparation for a tumor ablation procedure. PMID- 24238377 TI - "How we do it" - a practical approach to hepatic metastases ablation techniques. AB - Secondary liver malignancies are associated with significant mortality and morbidity if left untreated. Colorectal cancer is the most frequent origin of hepatic metastases. A multidisciplinary approach to the treatment of hepatic metastases includes medical, surgical, radiation and interventional oncology. The role of interventional oncology in the management of hepatic malignancies continues to evolve and applies to a large and continuous spectrum of metastatic disease, from the relatively small solitary metastasis to larger tumors and multifocal liver disease. Within the past 10 years, several publications of percutaneous image-guided ablation indicated the effectiveness and safety of this minimally invasive therapy for selected patients with limited number (arguably up to 4 metastases) of relatively small (less than 5cm) hepatic metastases. Different image-guided procedures such radiofrequency, microwave, and laser cause thermal ablation and coagulation necrosis or cell death of the target tumor. Cryoablation, causing cell death via cellular freezing, has also been used. Recently, irreversible electroporation, a nonthermal modality, has also been used for liver tumor ablation. In the following section, we review the different liver ablation techniques, as well as indications for ablation, specific patient preparations, and different "tricks of the trade" that we use to achieve safe and effective liver tumor ablation. We also discuss appropriate imaging and clinical patient follow-up and potential complications of liver tumor ablation. PMID- 24238378 TI - Renal tumor ablation. AB - Percutaneous, image-guided ablation for renal cell carcinoma (RCC) is an important treatment option for many patients. With more than 60,000 new cases every year and nearly three-fourths of those presenting as stage 1A, minimally invasive, nephron-sparing therapies have become the standard of care. Stage 1 A (<4cm, organ confined) disease presents the best scenario for percutaneous ablation. Various other factors influence the decision-making tree, such as patient age, life expectancy, comorbid condition, renal function, and the risk of metachronous lesions. Preparation aims at minimizing risks and has been discussed in detail. Computed tomography guidance remains the best option, and conscious sedation is adequate for most cases. Ultrasound and more recently magnetic resonance guidance are becoming viable alternatives. Whether radiofrequency or cryoablation are chosen, a margin of at least 5mm and up to 10mm is recommended. Various maneuvers required for optimum outcome, including hydrodissection and preoperative embolization are also discussed. Most renal ablations can be performed on an outpatient basis. Reasons to admit include complications, high risk patients, and the need for symptom management. Follow-up aims at (1) ensuring complete ablation and (2) monitoring against a metachronous lesion. For the former, a 3-month contrast computed tomography or magnetic resonance imaging is required and for the latter an annual examination is recommended. Though partial nephrectomy remains the gold standard, image-guided, percutaneous ablation for RCC can result in very similar outcomes. Over the last 10 years, there have been numerous studies reporting the efficacy and safety of ablation, and more recently, long-term studies have confirmed those numbers. Overall, the efficacy for percutaneous ablation for RCC stands at 90%-95% with a complication rate of 6%-7%. The most important factors for positive outcome are patient or tumor selection and operator experience. PMID- 24238379 TI - Percutaneous lung tumor ablation. AB - Percutaneous thermal ablation is a minimally invasive treatment for primary or secondary malignancies of the lung. Currently, 3 different modalities are available: radiofrequency, microwave, and cryoablation. Radiofrequency ablation remains to date the most developed although the other 2 modalities have their own distinct advantages. Percutaneous ablation can be used for treatment of stage 1 and 2 non-small cell lung carcinoma either alone or in combination with other therapies. Specifically, their noninvasive nature allows them to be used on patients who are otherwise deemed nonoperable. Percutaneous ablation can also be used to treat stage 3a non-small cell lung carcinoma in carefully selected patients. With nonlung primaries, percutaneous ablation can be used to control limited pulmonary metastasis, recurrences after alternative treatments, or to provide pain relief. Although the long-term data for percutaneous ablation is still being investigated, their noninvasive nature and efficacy will ensure their viability and evolution in the future. In this article we review the indications for percutaneous ablation, evaluation of the potential patient, an overview of the ablation options currently available, procedural details, potential complications, and expected results and follow-up. PMID- 24238380 TI - Ablation of musculoskeletal metastases: pain palliation, fracture risk reduction, and oligometastatic disease. AB - Thermal ablation is an effective, minimally invasive alternative to conventional therapies in the palliation of painful musculoskeletal metastases and an emerging approach to obtain local tumor control in the setting of limited metastatic disease. Various thermal ablation technologies have been applied to bone and soft tissue tumors and may be used in combination with percutaneous cement instillation for skeletal lesions with or at risk for pathologic fracture. This article reviews current practices of percutaneous ablation of musculoskeletal metastases with an emphasis on radiofrequency ablation and cryoablation of painful skeletal metastases. PMID- 24238381 TI - Image-guided ablation of adrenal tumors. AB - Adrenal neoplasms are a frequently encountered lesion, seen in approximately 4% 6% of patients undergoing diagnostic imaging studies. Although benign, nonfunctioning adenomas are the most common neoplasms of the adrenal, other primary tumors that affect the gland include myelolipomas, cortisol-producing adenomas, aldosteronomas, pheochromocytomas, and adrenocortical carcinomas. In addition, the adrenal gland is a common site of metastatic disease. Because the overall patient clinical picture varies with each one of these entities, there are a range of treatment options for adrenal tumors. Although surgical resection has been well described, the increased detection of incidental adrenal lesions because of widespread use of medical imaging and the need to treat patients with multiple comorbidities by using less invasive techniques has drawn greater attention to percutaneous ablative treatment of adrenal neoplasms. The purpose of this article is to review these techniques, which include percutaneous radiofrequency ablation, cryoablation, microwave ablation, and chemical ablation. PMID- 24238382 TI - Radiofrequency ablation for breast cancer. AB - Although breast-conserving therapy or mastectomy remains the gold standard for breast cancer treatment, minimally invasive alternatives to surgery are becoming more attractive for select patient populations. Advances in technology, reduced morbidity, improved cosmesis, and the ability to provide treatment in an outpatient setting are some of the advantages of image-guided therapy. Radiofrequency ablation (RFA) has been investigated because of its relatively low cost, low morbidity, and favorable technical success rates (76%-100% in published series). Image guidance during ablation involves the use of real-time ultrasound or magnetic resonance imaging to target the tumor and monitor the adequacy of ablation. Tumor size, location, histologic type, and reliable visualization under ultrasound (or other imaging modalities) are important to determine patient eligibility and procedural planning. In patients with localized breast cancer who decline surgery or are not candidates for surgery, RFA alone, or in combination with hormonal therapy, or followed by conventional radiation therapy with or without chemotherapy may prove to be viable treatment options. In patients with locally advanced or metastatic disease, RFA may be suitable for palliation of larger symptomatic tumors. Additional studies with long-term patient follow-up are necessary to better understand response to RFA and to determine its future role in the treatment algorithm for breast cancer. PMID- 24238383 TI - Irreversible electroporation: ready for prime time? AB - Image-guided ablation has evolved rapidly in the past decade into a competitive technique for treating focal solid malignancies. However, as they rely mainly on thermal energy, such as radiofrequency or microwave, many tumors close to sensitive organs, such as ducts, bowel, and nerves, still remain nonablatable owing to the risk of thermal injury. Irreversible electroporation is a novel ablation modality that relies largely on a nonthermal mechanism to induce cell death, and therefore may overcome many of the shortcomings of thermal ablation. Emerging preclinical data as well as early clinical experience is showing promise for this technique in treating a variety of tumors including periportal liver masses, pancreatic cancer, perihilar renal tumors, prostate cancer, and other soft tissue tumors. However, practical limitations remain for irreversible electroporation, and its complete cancer and location-specific safety and efficacy profiles are still largely unknown. We therefore review what is known for this new ablation modality based on preclinical and preliminary clinical data, and discuss its emerging indications as well as technical challenges. PMID- 24238384 TI - Image-guided fusion and navigation: applications in tumor ablation. AB - Navigation technology and multimodality image fusion represent an important development in interventional radiology. It is a rapidly developing field with great promise for improving, optimizing, and refining our workflow, especially for performing complex and difficult biopsies and ablations. It can potentially reduce procedure time, radiation dose, and complications while enhancing procedure accuracy and effectiveness. Additionally, such techniques are likely to greatly benefit less experienced operators and shorten the long learning curve to mastery of conventional procedures. Here, we describe different aspects of currently available image-guided fusion devices including the types of clinically available technological platforms (electromagnetic vs optical fusion) used to fuse prior and real-time images; pretest planning software; and advantages and limitations reported in preclinical and emerging clinical studies. Much refinement and development still needs to be performed for both the tracking systems and preablation software predictability, but this is anticipated as substantial research within the framework of multiple academic industrial partnerships is ongoing. PMID- 24238385 TI - Acute pain services; an Egyptian experience. PMID- 24238386 TI - Utilizing novel diversity estimators to quantify multiple dimensions of microbial biodiversity across domains. AB - BACKGROUND: Microbial ecologists often employ methods from classical community ecology to analyze microbial community diversity. However, these methods have limitations because microbial communities differ from macro-organismal communities in key ways. This study sought to quantify microbial diversity using methods that are better suited for data spanning multiple domains of life and dimensions of diversity. Diversity profiles are one novel, promising way to analyze microbial datasets. Diversity profiles encompass many other indices, provide effective numbers of diversity (mathematical generalizations of previous indices that better convey the magnitude of differences in diversity), and can incorporate taxa similarity information. To explore whether these profiles change interpretations of microbial datasets, diversity profiles were calculated for four microbial datasets from different environments spanning all domains of life as well as viruses. Both similarity-based profiles that incorporated phylogenetic relatedness and naive (not similarity-based) profiles were calculated. Simulated datasets were used to examine the robustness of diversity profiles to varying phylogenetic topology and community composition. RESULTS: Diversity profiles provided insights into microbial datasets that were not detectable with classical univariate diversity metrics. For all datasets analyzed, there were key distinctions between calculations that incorporated phylogenetic diversity as a measure of taxa similarity and naive calculations. The profiles also provided information about the effects of rare species on diversity calculations. Additionally, diversity profiles were used to examine thousands of simulated microbial communities, showing that similarity-based and naive diversity profiles only agreed approximately 50% of the time in their classification of which sample was most diverse. This is a strong argument for incorporating similarity information and calculating diversity with a range of emphases on rare and abundant species when quantifying microbial community diversity. CONCLUSIONS: For many datasets, diversity profiles provided a different view of microbial community diversity compared to analyses that did not take into account taxa similarity information, effective diversity, or multiple diversity metrics. These findings are a valuable contribution to data analysis methodology in microbial ecology. PMID- 24238387 TI - Recurrent involuntary imagery in people who stutter and people who do not stutter. AB - OBJECTIVE: To compare intrusive memories in groups of people who do (PWS), and who do not (PWNS), stutter. METHOD: Twenty-one participants who stuttered and 21 matched controls were given a semi-structured interview which explored imagery in speaking situations. The data were analyzed using a Content Analysis approach. Other outcome measures were the Beck Anxiety Inventory, the Beck Depression Inventory, the Post Traumatic Stress Disorder, PTSD, Symptom Scale: Self-Report Version. RESULTS: Significantly more stuttering participants than control participants indicated both recurrent imagery and associated memories. Content Analysis revealed themes of disfluency, anxiety, negative social evaluation, self focus and pressure to speak that were common to both groups' reports. Additional themes of helplessness, shame, sadness and frustration were found only in the images and memories of the stuttering group. No group differences were evident for the number of sensory modalities involved in images and memories, or for ratings of their vividness or strength of associated emotions, or on self-reports of depression, anxiety and trauma. CONCLUSIONS: Recurrent imagery about events in childhood is a potent factor in the memories of PWS. It is worth modifying interventions that have been successfully applied for treating social anxiety for use with people who stutter. EDUCATIONAL OBJECTIVES: After reading this article, participants will be able to: (a) identify the role of intrusive memories in psychiatric disorders and stuttering; (b) investigate how DSM criteria can be employed with people who stutter; (c) employ anxiety instruments used for assessing psychiatric disorders for stuttering; (d) distinguish between the intrusive memories experienced by people who stutter, and people who do not stutter; (e) apply treatments for intrusive memories in psychiatric disorders to work with people who stutter. PMID- 24238388 TI - Emotional reactivity and regulation in preschool-age children who stutter. AB - PURPOSE: This study experimentally investigated behavioral correlates of emotional reactivity and emotion regulation and their relation to speech (dis)fluency in preschool-age children who do (CWS) and do not (CWNS) stutter during emotion-eliciting conditions. METHOD: Participants (18 CWS, 14 boys; 18 CWNS, 14 boys) completed two experimental tasks (1) a neutral ("apples and leaves in a transparent box," ALTB) and (2) a frustrating ("attractive toy in a transparent box," ATTB) task, both of which were followed by a narrative task. Dependent measures were emotional reactivity (positive affect, negative affect), emotion regulation (self-speech, distraction) exhibited during the ALTB and the ATTB tasks, percentage of stuttered disfluencies (SDs) and percentage of non stuttered disfluencies (NSDs) produced during the narratives. RESULTS: Results indicated that preschool-age CWS exhibited significantly more negative emotion and more self-speech than preschool-age CWNS. For CWS only, emotion regulation behaviors (i.e., distraction, self-speech) during the experimental tasks were predictive of stuttered disfluencies during the subsequent narrative tasks. Furthermore, for CWS there was no relation between emotional processes and non stuttered disfluencies, but CWNS's negative affect was significantly related to nonstuttered disfluencies. CONCLUSIONS: In general, present findings support the notion that emotional processes are associated with childhood stuttering. Specifically, findings are consistent with the notion that preschool-age CWS are more emotionally reactive than CWNS and that their self-speech regulatory attempts may be less than effective in modulating their emotions. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) communicate the relevance of studying the role of emotion in developmental stuttering close to the onset of stuttering and (b) describe the main findings of the present study in relation to previous studies that have used different methodologies to investigate the role of emotion in developmental stuttering of young children who stutter. PMID- 24238389 TI - Nonword repetition and nonword reading abilities in adults who do and do not stutter. AB - PURPOSE: In the present study a nonword repetition and a nonword reading task were used to investigate the behavioral (speech accuracy) and speech kinematic (movement variability measured as lip aperture variability index; speech duration) profiles of groups of young adults who do (AWS) and do not stutter (control). METHOD: Participants were 9 AWS (8 males, Mean age=32.2, SD=14.7) and 9 age- and sex-matched control participants (Mean age=31.8, SD=14.6). For the nonword repetition task, participants were administered the Nonword Repetition Test (Dollaghan & Campbell, 1998). For the reading task, participants were required to read out target nonwords varying in length (6 vs. 11 syllables). Repeated measures analyses of variance were conducted to compare the groups in percent speech accuracy for both tasks; only for the nonword reading task, the groups were compared in movement variability and speech duration. RESULTS: The groups were comparable in percent accuracy in nonword repetition. Findings from nonword reading revealed a trend for the AWS to show a lower percent of accurate productions compared to the control group. AWS also showed significantly higher movement variability and longer speech durations compared to the control group in nonword reading. Some preliminary evidence for group differences in practice effect (seen as differences between the early vs. later 5 trials) was evident in speech duration. CONCLUSIONS: Findings suggest differences between AWS and control groups in phonemic encoding and/or speech motor planning and production. Findings from nonword repetition vs. reading highlight the need for careful consideration of nonword properties. EDUCATIONAL OBJECTIVES: At the end of this activity the reader will be able to: (a) summarize the literature on nonword repetition skills in adults who stutter, (b) describe processes underlying nonword repetition and nonword reading, (c) summarize whether or not adults who stutter differ from those who do not in the behavioral and kinematic markers of nonword reading performance, (d) discuss future directions for research. PMID- 24238390 TI - Stuttering prevalence, incidence and recovery rates depend on how we define it: comment on Yairi & Ambrose' article Epidemiology of stuttering: 21st century advances. PMID- 24238391 TI - Defining stuttering for research purposes. AB - This is a response to a Letter to the Editor entitled "Stuttering prevalence, incidence and recovery rates depend on how we define it: Comment on Yairi & Ambrose' article Epidemiology of Stuttering: 21st Century advances" by Paul Brocklehurst (2013). The criticism was directed specifically toward Yairi and Ambrose' conclusions, based on review of recent studies, regarding the incidence and prevalence of stuttering. In this response, Brocklehurst's arguments and suggestions of criteria for incidence research are discussed and negated. PMID- 24238392 TI - PROPER I: frequency and appropriateness of psychotropic drugs use in nursing home patients and its associations: a study protocol. AB - BACKGROUND: Nursing home patients with dementia use psychotropic drugs longer and more frequently than recommended by guidelines implying psychotropic drugs are not always prescribed appropriately. These drugs can have many side effects and effectiveness is limited. Psychotropic drug use between nursing home units varies and is not solely related to the severity of neuropsychiatric symptoms. There is growing evidence indicating that psychotropic drug use is associated with environmental factors, suggesting that the prescription of psychotropic drugs is not only related to (objective) patient factors. However, other factors related to the patient, elderly care physician, nurse and the physical environment are only partially identified. Using a mixed method of qualitative and quantitative research, this study aims to understand the nature of psychotropic drug use and its underlying factors by identifying: 1) frequency and appropriateness of psychotropic drug use for neuropsychiatric symptoms in nursing home patients with dementia, 2) factors associated with (appropriateness of) psychotropic drug use. METHODS: A cross-sectional mixed methods study. For the quantitative study, patients with dementia (n = 540), nursing staff and elderly care physicians of 36 Dementia Special Care Units of 12 nursing homes throughout the Netherlands will be recruited. Six nursing homes with high average rates and six with low average rates of psychotropic drug use, based on a national survey about frequency of psychotropic drug use on units, will be included. Psychotropic drugs include antipsychotics, anxiolytics, hypnotics, antidepressants, anticonvulsants and anti dementia drugs. Appropriateness will be measured by an instrument based on the Medication Appropriateness Index and current guidelines for treatment of neuropsychiatric symptoms. Factors associated to psychotropic drug use, related to the patient, elderly care physician, nurse and physical environment, will be explored using multilevel regression analyses. For the qualitative study, in depth interviews with staff will be held and analyzed to identify and explore other unknown factors. DISCUSSION: This study will provide insight into factors that are associated with the frequency and appropriateness of psychotropic drug use for neuropsychiatric symptoms. Understanding psychotropic drug use and its associations may contribute to better dementia care. PMID- 24238393 TI - Good cognitive performances in a child with Prader-Willi syndrome. AB - We report the case of a child affected by Prader-Willi syndrome (PWS) with good cognitive performances and without relevant behavioral abnormalities.The diagnosis of PWS, suspected on the basis of clinical features and past history, was confirmed by DNA methylation analysis. Additional genetic testing revealed a maternal uniparental disomy. Intellectual profile was analyzed by WISC-III and Raven's Progressive Matrices CPM, while the behavior was evaluated by K-SADS-PL and Child Behavior Checklist/4-18 to the parents.WISC-III test showed a Total Intelligence Quotient (T-IQ = 79) at the border level for age. The Verbal Intelligence Quotient (V-IQ) showed a lower score than the Performance Intelligence Quotient (P-IQ) (78 and 85, respectively). Raven's Matrices CPM showed an intelligence level at 75-90 degrees percentile for age. Concerning behavioral evaluation, a difficulty in impulse control was observed, with persistent but controllable search for food, without a clear psychopathological meaning. Also according to K-SADS-PL no areas of psychopathological dimensions were detected. In conclusion, in presence of consisting clinical features of PWS and high diagnostic suspicion, the diagnosis of PWS should be considered even in presence of a borderline IQ and in absence of psychopathological abnormalities. PMID- 24238394 TI - Protein conformational transitions at the liquid-gas interface as studied by dilational surface rheology. AB - Experimental results on the dynamic dilational surface elasticity of protein solutions are analyzed and compared. Short reviews of the protein behavior at the liquid-gas interface and the dilational surface rheology precede the main sections of this work. The kinetic dependencies of the surface elasticity differ strongly for the solutions of globular and non-globular proteins. In the latter case these dependencies are similar to those for solutions of non-ionic amphiphilic polymers and have local maxima corresponding to the formation of the distal region of the surface layer (type I). In the former case the dynamic surface elasticity is much higher (>60 mN/m) and the kinetic dependencies are monotonical and similar to the data for aqueous dispersions of solid nanoparticles (type II). The addition of strong denaturants to solutions of bovine serum albumin and beta-lactoglobulin results in an abrupt transition from the type II to type I dependencies if the denaturant concentration exceeds a certain critical value. These results give a strong argument in favor of the preservation of the protein globular structure in the course of adsorption without any denaturants. The addition of cationic surfactants also can lead to the non-monotonical kinetic dependencies of the dynamic surface elasticity indicating destruction of the protein tertiary and secondary structures. The addition of anionic surfactants gives similar results only for the protein solutions of high ionic strength. The influence of cationic surfactants on the local maxima of the kinetic dependencies of the dynamic surface elasticity for solutions of a non-globular protein (beta-casein) differs from the influence of anionic surfactants due to the heterogeneity of the charge distribution along the protein chain. In this case one can use small admixtures of ionic surfactants as probes of the adsorption mechanism. The effect of polyelectrolytes on the kinetic dependencies of the dynamic surface elasticity of protein solutions is weaker than the effect of conventional surfactants but exceeds the error limits. PMID- 24238395 TI - Gemini surfactants from natural amino acids. AB - In this review, we report the most important contributions in the structure, synthesis, physicochemical (surface adsorption, aggregation and phase behaviour) and biological properties (toxicity, antimicrobial activity and biodegradation) of Gemini natural amino acid-based surfactants, and some potential applications, with an emphasis on the use of these surfactants as non-viral delivery system agents. Gemini surfactants derived from basic (Arg, Lys), neutral (Ser, Ala, Sar), acid (Asp) and sulphur containing amino acids (Cys) as polar head groups, and Geminis with amino acids/peptides in the spacer chain are reviewed. PMID- 24238396 TI - High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples. AB - The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90.9%) and gp60 subtype in 605 (90.2%). It displayed excellent performance, with sensitivity and specificity values of 87.3 and 98.0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61.3 and 28.3%, respectively). 96.5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming. PMID- 24238397 TI - Effects of and satisfaction with short message service reminders for patient medication adherence: a randomized controlled study. AB - BACKGROUND: Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors. METHODS: We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group. RESULTS: After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group. CONCLUSIONS: Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule. PMID- 24238398 TI - Rapidly metastasizing malignant melanoma characterized by a rare BRAF mutation not responding to vemurafenib. PMID- 24238399 TI - Injection of a chemical castration agent, zinc gluconate, into the testes of cats results in the impairment of spermatogenesis: a potentially irreversible contraceptive approach for this species? AB - Male sterilization by chemical agents is a nonsurgical contraceptive approach designed to induce azoospermia and, therefore, infertility. Intratesticular injection of zinc gluconate for sterilization of dogs has been described, but its use in cats remains limited. The objective of the present study was to evaluate, by light and transmission electron microscopy, the efficacy of a single intratesticular injection of a zinc gluconate solution (Testoblock) as a sterilant for male cats. Twelve sexually mature mixed breed cats were allocated at random into two groups (control = 6; treated = 6) and given a single injection into each testis of either isotonic saline or zinc gluconate, respectively. Histopathologic and ultrastructural evaluation was assessed at 120 days postinjection. Histopathologic changes were not detected in the testes from the control group. However, histologic evaluation of the treated group revealed atrophic and dilated seminiferous tubules, a decrease in the number of germ cells, and incomplete spermatogenesis. Sertoli cells had various degrees of cytoplasmic vacuolization. Intertubular tissue revealed active fibroblasts, collagen deposition, and inflammatory cells. The diameter of seminiferous tubules, epithelial height and tubular area were reduced (P < 0.05) in the treated group compared with controls. Azoospermia occurred in 8 of the 11 treated cats (73%). Ultrastructural evaluation of Leydig cells revealed loss of nuclear chromatin, increased smooth endoplasmatic reticulum, and mitochondria degeneration. Intratesticular injection of zinc gluconate solution impaired spermatogenesis in cats and has great potential as a permanent sterilant in this species. PMID- 24238400 TI - Amount of maternal body fat significantly affected the quality of isolated mouse preimplantation embryos and slowed down their development. AB - The aim of our study was to investigate the effect of maternal obesity on the quality and developmental capabilities of in vivo-derived preimplantation embryos. A two-generation dietary model, based on mice overfeeding during intrauterine and early postnatal development, was used to produce four types of female animals: with physiological (7%-8%), slightly elevated (8%-11%), highly elevated (>11%), and low (<7%) amounts of body fat. Spontaneously ovulating females (5-6 weeks old) were mated with male animals and subjected to embryo isolation at Day 4. Stereomicroscopical evaluation of collected embryos showed that the amount of maternal body fat did not affect the average number of collected embryos per dam. However, significant differences were found in the stage-distribution of isolated embryos: dams with highly elevated body fat and dams with low fat delivered decreased numbers of blastocysts and increased numbers of lower-stage or degenerated embryos compared with dams with physiological or slightly elevated fat value. Fluorescence staining showed that blastocysts isolated from dams with high and low percentage of body fat contained significantly higher numbers of dead cells. Most of such dead cells were of apoptotic origin. In contrast, the amount of maternal body fat did not affect blastocyst growth-the average numbers of cells per blastocyst were comparable in all groups. In conclusion, highly elevated or decreased amount of maternal body fat slowed down the development and negatively affected the quality of naturally in vivo-derived preimplantation embryos. No negative effect of slightly elevated fat was observed. PMID- 24238401 TI - Effect of flunixin meglumine or prostaglandin E2 treatment 15 days after breeding on fertility in Saanen does. AB - The objective of this study was to determine the effects of timely injections of flunixin meglumine (FM) or vaginal application of prostaglandin E2 (PgE2) on pregnancy, fertility, fecundity, and prolificacy rates in Saanen goats. One hundred and sixty-three nonlactating Saanen does were treated with a flugestone acetate (20 mg)-containing intravaginal sponge for 12 days. They also received eCG (400 IU) and a PGF2alpha analogue (50 MUg) 10 days after progestagen priming. Does detected in estrus were mated and assigned randomly to one of three treatment groups. The PgE2 group (N = 40) received PgE2 (2.5 mg) intravaginally 15 days after mating. The FM group (N = 54) received flunixin meglumine (total dose, 100 mg) intramuscularly 15 days after mating. Flunixin meglumine was administered at 9:00 AM. Animals in the control group (N = 69) received no treatment. Pregnancy was diagnosed using transrectal ultrasonography (B-mode at 8 MHz) 30 days after mating. The pregnancy rate was significantly greater (P < 0.01) after 30 days in goats treated with PgE2 and also in the control group than in those treated with FM (67.5%, 59.4%, and 42.5%, respectively). The pregnancy rate did not differ between the PgE2 and the control group. The pregnancy and fertility rate were lowest in the FM group compared with the other groups. There was no significant difference in the prolificacy rate among experimental groups. In conclusion, our results showed that FM administration during a late luteal phase is detrimental to early pregnancy in goats. PMID- 24238402 TI - Bioinformatic analysis to find small molecules related to rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints. AIMS: Our aim is to explore the change of gene expression profile in patients with RA, and investigate the underlying mechanism of the pathogenesis and progression of RA. METHODS: We downloaded the dataset GSE2053 from Gene Expression Omnibus database and screened the differentially expressed genes by analyzing the profiles between RA and normal cells with bioinformatics methods. Furthermore, Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to screen GO and the significantly changed signaling pathways in RA cells with the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: By bioinformatics methods, we obtained the metabolic pathway changed in the cells of patients with RA, and explored small molecule drugs that can restore these changes. CONCLUSIONS: These results may provide a new approach for explore the pathogenesis of RA and a new breakthrough in the medical treatment of patients with RA. PMID- 24238403 TI - Pattern of HIV testing and multiple sexual partnerships among men who have sex with men in China. AB - BACKGROUND: Men who have sex with men (MSM) are a hidden but emerging population susceptible to HIV infection against a background of rapidly increasing HIV prevalence in China. Low HIV testing levels and multiple partnerships among MSM are two major contributing factors to HIV transmission. METHODS: We conducted a cross-sectional survey among 447 Chinese MSM in Changsha and Tianjin cities from November to December 2011 using an anonymous questionnaire. We aim to investigate (1) the trend of HIV testing rates among Chinese MSM during 2009 to 2011; and (2) the patterns of multiple sexual relationships with male, female and commercial partners. RESULTS: The self-reported past-12-months HIV testing level among Chinese MSM increased from 16.6% in 2009 to 46.3% in 2010 and 58.6% in 2011 (chi(2) = 173.49, p < 0.001). Compared with men who have tested for HIV, the never-tested MSM were generally younger, never married, students, and more likely to have unprotected anal intercourse with non-commercial male partners. Furthermore, 21.3% (56/263) MSM reported having multiple regular male and female sexual partnerships and 6.2% (16/257) reported having commercial male partners in the past six months. However, individuals who were never-tested for HIV are consistently less likely to engage in multiple sexual relationships. CONCLUSIONS: HIV testing rates have increased substantially among Chinese MSM in the period 2009-2011, although significant barriers to testing remain. Multiple sexual partnerships, and especially bisexual behaviours, are common among Chinese MSM. PMID- 24238404 TI - Changing monsoon patterns, snow and glacial melt, its impacts and adaptation options in northern India: setting the stage. AB - To set the stage of this special issue this paper gives a short introduction to the sensitivity to climate change of the main bio-physical processes in the Hindukush-Karakoram-Himalayas. It also describes the socio-economic setting of the Ganges basin in northern India as the main focal point of the impact and adaptation studies in this special issue. PMID- 24238405 TI - Cytokine signaling-1 suppressor is inducible by IL-1beta and inhibits the catabolic effects of IL-1beta in chondrocytes: its implication in the paradoxical joint-protective role of IL-1beta. AB - INTRODUCTION: Although IL-1beta is believed to be crucial in the pathogenesis of osteoarthritis (OA), the IL-1beta blockade brings no therapeutic benefit in human OA and results in OA aggravation in several animal models. We explored the role of a cytokine signaling 1 (SOCS1) suppressor as a regulatory modulator of IL 1beta signaling in chondrocytes. METHODS: Cartilage samples were obtained from patients with knee OA and those without OA who underwent surgery for femur-neck fracture. SOCS1 expression in cartilage was assessed with immunohistochemistry. IL-1beta-induced SOCS1 expression in chondrocytes was analyzed with quantitative polymerase chain reaction and immunoblot. The effect of SOCS1 on IL-1beta signaling pathways and the synthesis of matrix metalloproteinases (MMPs) and aggrecanase-1 was investigated in SOCS1-overexpressing or -knockdown chondrocytes. RESULTS: SOCS1 expression was significantly increased in OA cartilage, especially in areas of severe damage (P < 0.01). IL-1beta stimulated SOCS1 mRNA expression in a dose-dependent pattern (P < 0.01). The IL-1beta induced production of MMP-1, MMP-3, MMP-13, and ADAMTS-4 (aggrecanase-1, a disintegrin and metalloproteinase with thrombospondin motifs 4) was affected by SOCS1 overexpression or knockdown in both SW1353 cells and primary human articular chondrocytes (all P values < 0.05). The inhibitory effects of SOCS1 were mediated by blocking p38, c-Jun N-terminal kinase (JNK), and nuclear factor kappaB (NF-kappaB) activation, and by downregulating transforming growth factor beta-activated kinase 1 (TAK1) expression. CONCLUSIONS: Our results show that SOCS1 is induced by IL1-beta in OA chondrocytes and suppresses the IL-1beta induced synthesis of matrix-degrading enzymes by inhibiting IL-1beta signaling at multiple levels. It suggests that the IL-1beta-inducible SOCS1 acts as a negative regulator of the IL-1beta response in OA cartilage. PMID- 24238406 TI - Looks like smoking, is it smoking?: children's perceptions of cigarette-like nicotine delivery systems, smoking and cessation. AB - BACKGROUND: Alternative cigarette-like nicotine delivery systems have been met with diverse opinions. One concern has been for the effect on children. We investigate whether children can differentiate tobacco cigarette smoking from use of a nicotine inhaler and electronic cigarette. Their opinions on these devices was also of interest. METHODS: Two structured focus groups and twelve individual interviews were conducted with twenty Maori and Pacific children (6-10 years old) in low socioeconomic areas in Auckland, New Zealand. Children viewed short video clips on an iPad that demonstrated an actor smoking a tobacco cigarette, sucking a lollipop or using an electronic cigarette or a nicotine inhaler. RESULTS: Children did not recognise the inhaler or electronic cigarette. Some children did however notice anomalies in the 'smoking' behaviour. Once told about the products the children were mostly positive about the potential of the inhaler and electronic cigarette to assist smokers to quit. Negative perceptions were expressed, including views about the ill health effects associated with continued nicotine intake and the smoker's inability to quit. CONCLUSIONS: In a context unfamiliar with electronic cigarettes or nicotine inhalers, such as New Zealand, children may misperceive use of these products as smoking. Once these products are more common and the purpose of them is known, seeing people use them should normalise quitting behaviour, something the children were very supportive of. PMID- 24238407 TI - [Coverage errors of five shade guide systems to vital natural teeth]. AB - OBJECTIVE: To compare the coverage errors (CE) of five different shade guides in anterio vital natural teeth of selected people. METHODS: Anterior vital natural teeth were measured with Crystaleye spectrophotometer, color coordinates of the teeth and five shade guides A (VITA Classical), B (VITA 3D-Master), C (Chromascop), D (Shofu Vintage Halo NCC) and E (Noritake)were analyzed with the supporting software. The CE of the five shade guide systems to natural teeth were evaluated in cervical, body and incisal regions, and difference in CE among shade guides was determined. RESULTS: In the cervical region, shade guide A had the maximal CE value (3.09 +/- 0.97) and shade guide D had the minimal CE value (1.62 +/- 0.75).In the body region, CE of shade guide B (1.65 +/- 0.64) and shade guide D (1.52 +/- 0.74) were lower than those of shade guides A (2.04 +/- 0.80), C (2.04 +/- 0.90) and E (2.02 +/- 0.84) (P < 0.05).In the incisal part, all CE were below 2.00, and again shade guide A had the maximal CE value (1.81 +/- 0.86) and shade guide D had the minimal CE value (1.28 +/- 0.55). CONCLUSIONS: Within the limitation of the study, shade guide D had better color coverage of natural teeth in cervical, body and incisal regions. PMID- 24238408 TI - [Effect of hydrogen peroxide with different pH values on the color, translucency and laser-induced fluorescence of human dentin]. AB - OBJECTIVE: To investigate the effect of 30% hydrogen peroxide(HP) with different pH values on color, translucency and laser-induced fluorescence of human dentin. METHODS: Sixty dentin specimens from crown of mandibular third molars were randomly assigned into four groups (n = 15) and treated with acidic 30% HP, neutral 30% HP, alkaline 30% HP and deionized water (control group), respectively. The bleaching process was 0.5 h*4 times, and time points for measuring were baseline (0), 0.5, 1 and 2 h. A colorimeter was employed to measure the L(*), a(*), b(*) coordinates of dentin against white, black and yellow background. Then the parameters of translucency, masking effects, chroma and whiteness were calculated. The dentinal laser-induced Raman/fluorescence spectra was recorded by a Raman spectrometer and the fluorescence intensity(FI) and FI% were calculated. RESULTS: DeltaFI of acidic, neutral, alkaline 30% HP at 2 h were 9960.03 +/- 2037.74, 8502.09 +/- 1413.86, 8554.29 +/- 1986.19. And DeltaFI% were 84.60 +/- 3.43, 84.89 +/- 5.19, 86.72 +/- 2.65, respectively. Repeated measure of ANOVA revealed that all parameters in the bleaching groups were significantly influenced by time (P < 0.001). Compared with control group, bleaching resulted significant change of DeltaTP, Deltachroma, Deltawhiteness, DeltaL(*), Deltaa(*), Deltab(*), DeltaE, DeltaFI and DeltaFI% (P < 0.001). There was no significant difference between three bleaching groups on DeltaTP, Deltamasking effects, Deltachroma, Deltawhiteness, DeltaL(*), Deltab(*), DeltaE, DeltaFI and DeltaFI%. Correlation analysis demonstrated that FI was associated with chroma, a(*), b(*) and whiteness, respectively, and DeltaFI was associated with DeltaTP, Deltamasking effects, Deltawhiteness, Deltachroma, Deltab(*) and DeltaE. CONCLUSIONS: 30% HP with different pH values could result in the same change of the color, translucency and laser-induced fluorescence of human dentin.Laser-induced fluorescence was associated with dentinal color and translucency, which might be a novel way to investigate the bleaching mechanism of dentin. PMID- 24238409 TI - [Preliminary study on tactile function of implant-supported single crowns]. AB - OBJECTIVE: To measure passive tactile threshold of implant-supported single crowns (ISSC) in six orthogonal orientations, to analyze impact factors, and to guide the occlusal adjustment in a personalized manner. METHODS: The passive tactile thresholds of 24 implant-supported single crowns (5 maxillary anterior teeth, 7 maxillary posterior teeth and 12 mandibular posterior teeth) from 19 ISSC patients (8 men and 11 women, from 25 years old to 56 years old) were measured in six orthogonal orientations (four horizontal orientations of labial or buccal, lingual, mesial and distal, and two axial orientations of apical and coronal) using a digital test system for tactile function of teeth.SPSS 19.0 for windows was used to analyze impact factors, using double-sided test, with a significance level of 0.05. Paired-samples t test was used to test the difference between implant-supported single crowns and the controlled natural teeth, and between different time points. One-way ANOVA was used to test the difference between different orientations, maxilla-mandibular anterior-posterior, and men women. RESULTS: The passive tactile thresholds of ISSC and control teeth were (1282 +/- 709) and (40 +/- 40) mN respectively. The difference was of statistical significance (P < 0.001). The passive tactile thresholds of buccal-lingual, mesial-distal and axial of ISSC were (1334 +/- 696), (1102 +/- 605) and (1412 +/- 791) mN respectively, of which, the difference between mesial-distal and axial was of statistical significance (P < 0.05). The passive tactile thresholds of ISSC of maxillary anterior teeth, posterior teeth and mandibular posterior teeth were (1003 +/- 616), (1302 +/- 620) and (1386 +/- 769) mN respectively, of which, the difference between maxillary anterior teeth and posterior teeth was of statistical significance (P < 0.05). The passive tactile thresholds of ISSC of men and women were (1751 +/- 784) and (946 +/- 393) mN respectively, the difference was of statistical significance (P < 0.001). The passive tactile thresholds of ISSC of one-week and one-month after wearing the teeth were (1421 +/- 826) and (1411 +/- 814) mN respectively, the difference was of no statistical significance (P > 0.05). CONCLUSIONS: The passive tactile threshold of ISSC was more than 65 times as much as that of the natural teeth. There was statistical significance between different orientations, between maxillary anterior and posterior teeth, and between men and women. No statistical significance was found between maxillary and madibular posterior teeth and between one-week and one month after wearing the teeth. PMID- 24238410 TI - [Effect of hydrofluoric acid etching time and resin bonding on the flexural strength of lithium disilicate glass ceramic]. AB - OBJECTIVE: To analyze the effect of hydrofluoric acid(HFA) etching time and resin bonding on the flexural strength of IPS e.max(r) Press glass ceramic, and evaluate the efficacy of resin cements to seal the cracks of the etched ceramic. METHODS: Two hundred and twenty-five bars (25.0 mm*3.0 mm*2.0 mm) were made from IPS e.max(r) Press ingots using lost-wax, hot-pressed ceramic fabrication technology and randomly divided into five groups, forty-five each.In each group, the surfaces of ceramic bars were etched by 9.5% HFA gel for 0, 20, 40, 60 and 120 s respectively. Three specimens from each group were selected to observe the microstructure by the field emission scanning electron microscope (FE-SEM). Then each group were randomly subdivided into two subgroups (n = 20).One subgroup were coverd with a thin (approximately 0.1 mm) layer of resin cement (Variolink N), whereas the other subgroup remained unaltered.Half of the specimens were stored in 37 degrees C water bath for 24 h and the other half went through thermocycle 10 000 times before 3-point bending test to determine their flexural strength.Interfaces between resin cement and etched ceramic were examined with FE SEM. RESULTS: FE-SEM results showed that etching with HFA resulted in preferential dissolution of glass ceramic, and partially supported crystals within the glass matrix were lost with the increasing of etching time.FE-SEM indicated that resin cement sealed the cracks and defects and bonded tightly to etched ceramic surface. The mean flexural strength values of group 0, 20, 40, 60 and 120 s were (384 +/- 33), (347 +/- 43), (330 +/- 53), (327 +/- 67) , and (317 +/- 41) MPa respectively. The mean flexural strength of each group except group 0 s increased significantly to (420 +/- 31), (435 +/- 50), (400 +/- 39), and (412 +/- 58) MPa respectively after the application of resin cement. CONCLUSIONS: Overtime HFA etching could have a wakening effect on IPS e.max(r) Press glass ceramic. The application of dual-curing resin cement can compensate the strength loss of the etched glass ceramic. PMID- 24238412 TI - [Comparative analysis of the relationship between of chronic periodontitis patients' compliance and clinical efficacy]. AB - OBJECTIVE: To evaluate the effect of patients' compliance on clinical parameters in patients with chronic periodontitis during periodontal maintenance therapy period. METHODS: Chronic periodontitis patients who had completed non-surgical periodontal basic treatment were incorporated into the periodontal maintenance therapy(PMT). Clinical examination was performed in the baseline and each quarterly recall, over 3-year period. Clinical parameters including number of teeth, probing depth(PD), attachment loss(AL) level and bleeding on probing(BOP), were recorded. According to the number of PMT visit, the patients were classified into three groups:regular complier(RC); erratic complier(EC); non-complier(NC). The final parameters(three years later) were obtained by outpatient follow-up and telephone interviews. The data were calculated for the pecentage of sites with PD 4-5 mm, PD >= 6 mm, AL 4-5 mm, AL >= 6 mm, BOP, and the number of tooth loss per patient and the rates of progression of periodontitis.Statistical analyses including ANOVA test and Chi-square test were performed by SPSS 16.0 software package. RESULTS: The percentage of clinical parameters in RC [AL 4-5 mm :(14.8 +/- 5.0)%, AL >= 6 mm: (9.3 +/- 3.1)%, BOP: (22.8 +/- 4.2)%] were significantly decreased compared with that at baseline [AL 4-5 mm:(19.0 +/- 6.0)%, AL >= 6 mm: (10.6 +/- 3.1)%, BOP:(30.3 +/- 5.6)%] (P < 0.01). There was significant difference between RC and NC [AL 4-5mm:(43.3 +/- 1.3)%, AL >= 6 mm:(31.3 +/- 1.7)%, BOP (91.5 +/- 5.4)%] (P < 0.01), and between RC and EC[AL 4-5 mm: (18.9 +/ 6.7)%, AL >= 6 mm: (12.6 +/- 5.4)%, BOP:(38.4 +/- 5.2)%] (P < 0.05). The progression rate of periodontitis [19.1% (4/21) at subject level, 0.7% (434/61 362) at site level] and tooth loss (1.0) was significantly lower in RC compared with EC and NC patients. CONCLUSIONS: Regular periodontal maintenance enables the patients with chronic periodontitis to maintain long-term efficacy. PMID- 24238411 TI - [Long-term clinical and hematologic effects of non-surgical treatment on aggressive periodontitis]. AB - OBJECTIVE: To investigate the long-term effects of non-surgical treatment on clinical and hematologic states of patients with generalized aggressive periodontitis (GAgP). METHODS: Patients with GAgP (n = 25) and healthy controls (n = 28) were recruited. The clinical parameters, including probing depth (PD), bleeding index (BI), attachment loss (AL) were examined and recorded. Blood cell variables, including white blood cells (WBC), leukocyte, neutrophil, and lymphocyte counts, as well as serum triglycerides, fasting glucose and protein parameters, including total protein, albumin, globulin, and albumin/globulin ratio (A/G), were analyzed. Twenty-five GAgP patients received non-surgical treatment and the clinical and blood parameters 3 to 7 years after treatment were re-evaluated. Clinical and hematological parameters of the two groups were compared. Comparisons of clinical and hematologic parameters pre- and post treatment in GAgP group were performed through one-way ANOVA and paired-t test. RESULTS: Elevated white blood cells, neutrophil numbers and serum total protein, globulin levels were observed in patients with GAgP compared to controls[(6.3 +/- 2.0)*10(9)cell/L vs.(5.4 +/- 1.0)*10(9)cell/L, (4.1 +/- 1.8)*10(9) cell/L vs.(3.0 +/- 0.9)*10(9) cell/L, (78.2 +/- 4.4) g/L vs. (75.6 +/- 4.6) g/L and (29.3 +/- 3.8) g/L vs.(26.5 +/- 3.9) g/L respectively, P < 0.05]. A/G ratio was lower in the GAgP group than in the control group (1.7 +/- 0.2 vs.1.9 +/- 0.3, P < 0.01). Three to seven years after periodontal treatment, the reduction of PD and BI was observed in GAgP group(P < 0.05). There were significant decreases of WBC count, neutrophil count, serum total protein and globulin level, and significant increases of albumin level and A/G at 3 to 7 years after treatment(P < 0.05). CONCLUSIONS: Non-surgical treatment may have long-term beneficial effect on the periodontal clinical status and hematologic parameters of generalized aggressive periodontitis. PMID- 24238413 TI - [Microscopic Raman spectral characteristics and diagnostic value of pathological lip minor salivary glands affected in primary Sjogren's syndrome]. AB - OBJECTIVE: To investigate the Raman spectral characteristics of the pathological lip minor salivary glands affected in primary Sjogren's syndrome. METHODS: Thirty pathological samples and 30 normal samples were collected in this study. The samples were examined by Raman microscope.Support vector machine(SVM) was employed to analyze the data and establish the classification model. RESULTS: The spectra of pathological tissues was different from the controls in proteins, nucleic acids, lipids and glycogen skeleton. The sensitivity, specificity and accuracy of the model established by SVM on the training sets were all 92.0% (92/100), but the sensitivity, specificity and accuracy of the model established by SVM on the testing sets were 69.2% (37/53), 100.0% (37/37) and 82.0% (73/89) respectively. CONCLUSIONS: There was significant difference in Raman spectra between the pathological and normal lip salivary glands, and the classification model established by SVM could discriminate the pathological glands from the normal ones. PMID- 24238414 TI - [Expression of microRNA-31 and its clinicopathologic significance in oral squamous cell carcinoma]. AB - OBJECTIVE: To investigate the expression of microRNA-31 and its association with clinicopathologic features in oral squamous cell carcinoma (OSCC). METHODS: The expression level of microRNA-31 in 62 cases of OSCC and matched non-tumor adjacent tissue specimens was examined using stem-loop real-time PCR. The relationship between the expression of microRNA-31 and its clinicopathologic features of OSCC was analyzed. RESULTS: The expression of microRNA-31 was significantly higher in the tumor tissues than that in the adjacent tissues (P < 0.05).Up-regulated microRNA-31 expression was associated with the lymph node metastasis (P < 0.05) and cell differentiation (P < 0.05) in OSCC patients.No significant association was found between the expression of microRNA-31 and gender, age, lymph node metastasis, tumor size and location.Receiver operator characteristic curve (ROC) of microRNA-31 about cell differentiation resulted in a diagnostic sensitivity of 70.4% and specificity of 89.5%. CONCLUSIONS: The up regulated level of microRNA-31 expression may be related to the pathogenesis of OSCC. PMID- 24238415 TI - [Expression of quorum-sensing related genes during Enterococcus faecalis biofilm formation]. AB - OBJECTIVE: To investigate the relationship between the expression of the quorum sensing related genes during Enterococcus faecalis(Ef) biofilm formation. METHODS: Ef biofilms model was established in vitro and film formation process was observed by confocal laser scanning microscope at 6, 12, 24 and 48 hours respectively.Quantification of biofilms was achieved by staining with crystal violet.Real-time fluorescence quantitative PCR method was used to detect the expression of fsrB, gelE and sprE genes in the process of Ef biofilm formation. RESULTS: A lot of live and dead bacteria unevenly distributed in Ef biofilm. The quantity of biofilms increased with time within 24 hours and was 0 h:0.00 +/- 0.00, 6 h:1.09 +/- 0.13, 12 h:2.10 +/- 0.79, 24 h:3.30 +/- 0.13, which was significantly different among the 4 time period(P < 0.05). The quantity of biofilm at 48 h(3.51 +/- 0.01) increased slightly compared with 24 h(3.30 +/- 0.13) , but did not show significant difference.Quantitative real-time PCR showed that the expression of quorum-sensing related fsrB increased with time within 24 hours and was 0 h:9.98 +/- 0.46, 6 h:23.45 +/- 1.13, 12 h:47.30 +/- 2.49, 24 h: 331.30 +/- 2.18, which was significantly different among the 4 time period(P < 0.05). The expression of gelE was 0 h: 6.54 +/- 0.73, 6 h: 14.26 +/- 1.24, 12 h: 37.47 +/- 2.35, 24 h:264.80 +/- 5.10(P < 0.05). The expression of sprE was 0 h: 7.72 +/- 0.74, 6 h: 21.15 +/- 0.96, 12 h:49.87 +/- 3.18, 24 h:441.89 +/- 7.74, which was significantly different among the 4 time period(P < 0.05). CONCLUSIONS: The fsrB, gelE and sprE genes are closely related to the biofilm formation in Ef. PMID- 24238416 TI - [Identification of mutation in PAX9 gene in a Mongolian family with non-syndromic oligodontia]. AB - OBJECTIVE: To investigate the mutation in transcription factor paired box gene PAX9 in a mongolian family with non-syndromic oligodontia. METHODS: Peripheral blood was collected from 17 core family members (9 unaffected, 8 affected) in this Mongolian family with non-syndromic oligodontia. Mutation in exons of PAX9 gene was identified by PCR amplification and DNA sequencing. RESULTS: A point mutation c.87G > C at position 87 in exon 4 of PAX9 was identified from 8 affected members in the family, which were G/C heterozygous.While the 9 healthy members in the family were homozygous for C which was consistent with normal reference sequence in the GenBank(accession number: NC_000014). CONCLUSIONS: The mutation of c.87G > C (p. Ala240Pro) in exon 4 of PAX9 was likely to cause the non-syndromic oligodontia in this Mongolian family. PMID- 24238417 TI - [An experimental study on mineral triozide aggregate and calcium hydroxide-based paste applied to direct pulp capping in rat]. AB - OBJECTIVE: To evaluate the volume change of rat root following direct pulp capping with mineral triozide aggregate(MTA) and calcium hydroxide-based paste (Vitapex) . METHODS: Sixty-four female, 1-month-old Wistar rats were randomly divided into 4 groups, MTA group, Vitapex group, model group and control group, 16 rats in each group. The right maxillary first molar was taken as experimental tooth and control tooth. The exposed pulp was capped separately with MTA and calcium hydroxide after the pulp had been exposed mechanically, while nothing done to the control group. Using micro-CT and three-dimensional reconstruction techniques, the volume change of rat root was evaluated at 1, 2, 4 weeks and 6 weeks after direct pulp capping. The data were analyzed by an way ANOVA analysis followed by a LSD-t test. RESULTS: The root volume in the MTA group[(1.08 +/- 0.07), (1.32 +/- 0.18) mm(3)] was significantly smaller than that in the Vitapex group[(1.28 +/- 0.16), (1.59 +/- 0.18) mm(3)] at 2 and 4 weeks after operation (P < 0.05) . At the sixth week , there was no significant difference between the MTA group [(1.36 +/- 0.03) mm(3)] and the Vitapex group[(1.61 +/- 0.31) mm(3)] (P > 0.05) . The root volume in the MTA group and Vitapex group was significantly larger than that in the model group [(0.87 +/- 0.09), (1.01 +/- 0.17) , (1.02 +/- 0.25) mm(3)] from the second to sixth week after operation (P < 0.05) . CONCLUSIONS: MTA and Vitapex can effectively promote root formation and growth and can be used as biological pulp-capping material. PMID- 24238418 TI - [Recommendation on improving the formulation and statistical methods of fistula post-palatoplasty incidence]. PMID- 24238419 TI - [Clinical application of two kinds of flaps taken from the transverse cervical vessels system]. PMID- 24238420 TI - [Temporomandibular joint reconstruction retrospect and prospect]. PMID- 24238421 TI - [The 7th national conference of prosthodontics]. PMID- 24238422 TI - [Proceedings of national symposium on postgraduates education in stomatology]. PMID- 24238423 TI - Antibiotic resistance--a call to arms for primary healthcare providers. PMID- 24238424 TI - A framework for the non-antibiotic management of upper respiratory tract infections: towards a global change in antibiotic resistance. AB - Antibiotic resistance has become a critical health issue on a global scale, with much of the problem resulting from inappropriate use of antibiotics in primary care. To change this practice, the global respiratory infection partnership has formulated a pentagonal (five P) framework for the non-antibiotic management of upper respiratory tract infections (URTIs) - one of the most common conditions in primary care for which antibiotics are prescribed. The framework presents the rationale for focusing on URTIs to promote antibiotic stewardship in primary care and elaborates on five key areas to focus on to bring about change: policy, prevention, prescribers, pharmacy and patients. The ultimate aim is to adopt a patient-centred symptomatic management strategy using a flexible framework that can be adapted across countries to create a consistent global approach to change behaviour. PMID- 24238425 TI - Sore throat: effective communication delivers improved diagnosis, enhanced self care and more rational use of antibiotics. AB - The majority of throat infections are of viral origin and resolve without antibiotic treatment. Despite this, antibiotic use for sore throat infections remains high, partly because it is difficult to determine when antibiotics may be useful, on the basis of physical findings alone. Antibiotics may be beneficial in bacterial throat infections under certain clinical and epidemiological circumstances; however, even many of those infections in which bacteria play a role do resolve just as quickly without antibiotics. Furthermore, non-medical factors such as patient expectations and patient pressure are also important drivers of antibiotic use. To address these issues, a behavioural change is required that can be facilitated by improved communication between primary healthcare providers and patients. In this article, we provide doctors, nurses and pharmacy staff, working in primary care or in the community, with a structured approach to sore throat management, with the aim of educating and empowering patients to self-manage their condition. The first component of this approach involves identifying and addressing patients' expectations and concerns with regard to their sore throat and eliciting their opinion on antibiotics. The second part is dedicated to a pragmatic assessment of the severity of the condition, with attention to red-flag symptoms and risk factors for serious complications. Rather than just focusing on the cause (bacterial or viral) of the upper respiratory tract infections as a rationale for antibiotic use, healthcare providers should instead consider the severity of the patient's condition and whether they are at high risk of complications. The third part involves counselling patients on effective self-management options and providing information on the expected clinical course. Such a structured approach to sore throat management, using empathetic, non-paternalistic language, combined with written patient information, will help to drive patient confidence in self-care and encourage them to accept the self-limiting character of the illness - important steps towards improving antibiotic stewardship in acute throat infections. PMID- 24238426 TI - Comment on: "Marek et al. CT scan-detected pneumoperitoneum: an unreliable predictor of intra-abdominal injury in blunt trauma. Injury (2013) [Epub ahead of print]". PMID- 24238427 TI - Diaphragm motion and lung function prediction in patients operated for lung cancer--a pilot study on 27 patients. AB - BACKGROUND: The influence of the diaphragm motion to the accuracy of postoperative lung function prediction after the lung resction is still debatable. METHODS: Prospective study that included 27 patients who underwent a lung resection for cancer. Diaphragm movements were assessed radiographically and by ultrasonography before the operation and postoperatively, with the lung fully expanded. The relationship between the diaphragm movements and differences between ppo FEV1 and measured postoperative FEV1, was analysed by expressing diaphragm movements as preoperative diaphragm amplitudes, preoperative postoperative amplitude differences or in relation to fixed intrathoracic distances. RESULTS: The mean difference between preoperative and postoperative diaphragm amplitudes of the diseased side was 2.42 +/- 1.25 cm and 2.11 +/- 2.04 cm when measured radiographically and by ultra sound respectively (p > 0.05). A significant positive correlation was found for the entire group only between the patients' height and the differences ppo FEV1 - actual FEV1: the prediction was more unprecise in taller patients. With the cut-off value of 550 ml for differences between ppo FEV1 and actual FEV1, a significant inverse correlation was found only if the preoperative ipsilateral diaphragm amplitude was presented as a percentage of the preoperative apex-base distance in inspiration. For right sided tumours, the greater the difference between preoperative and postoperative ipsilateral diaphragm amplitudes, the greater discrepancy between predicted and actual postoperative FEV1. For left-sided tumours, inverse correlation existed if the preoperative diaphragm amplitude was presented as a percentage of the preoperative distance apex-base. CONCLUSION: Diaphragm movements influence the accuracy of the postoperative lung function prediction. PMID- 24238428 TI - Diagnostic challenges of composite colorectal tumors of adenoma-mantle cell lymphoma type. AB - Composite intestinal tumors of adenoma-lymphoma type are rare. To our knowledge 1 tumor showing this association has been previously reported, the histologic diagnosis being made retrospectively. We report the case of an 80-year old male patient complaining for epigastric pain, rectorrhagia, diarrhea, and weight loss. At endoscopy, a rectal lesion (3 cm) of villous low-grade dysplasia adenoma type was detected. Due to persistence of symptoms, new gastro- and coloscopies were performed, the biopsies showing low-grade dysplasia adenomas (right colon, and rectum) and an abundant lymphoid infiltrate (gastroduodenal anastomosis, small intestine, sigmoid, right and left colon, transverse colon, and rectum) of mantle cell lymphoma type, the rectal polyp being composed of both tumor types. The muscularis mucosa was focally infiltrated by the lymphoma, the bulk of the lymphoma being submucosal. After the treatment of 8 mini-cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone cures, lymphoma persisted. On endoscopic ultrasound examination, after the 6 cures of bendamustine following the cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone treatment, the signal of the rectal villous lesion disappeared in the peripheral layers, including of the muscular layer, suggestive of an invasive lesion or persistence of lymphoma. Biopsies confirmed the persistence of the rectal adenoma with low and high-grade adenoma, without lymphoma. In conclusion, the biopsic diagnosis of composite intestinal tumors of adenoma-mantle cell lymphoma type may be challenging, the bulk of the lymphoma being submucosal as in the present case. Although the malignant tumor treatment is the priority in such cases, the effects of chemotherapy on the evolution of benign tumors such as adenomas should be carefully assessed. PMID- 24238429 TI - Transcriptomic analysis of genetically defined autism candidate genes reveals common mechanisms of action. AB - BACKGROUND: Austism spectrum disorder (ASD) is a heterogeneous behavioral disorder or condition characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a core clinical disability. METHODS: Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA constructs. Whole genome expression analysis was conducted for each of the knockdown cultures as well as a mock transduced culture and a culture exposed to a lentivirus expressing an anti luciferase shRNA. Gene set enrichment and a causal reasoning engine was employed to identify pathway level perturbations generated by the transcript knockdown. RESULTS: Quantification of the shRNA targets confirmed the successful knockdown at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long term potentiation, and synaptic activity. CONCLUSIONS: This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients. PMID- 24238431 TI - Testicular migration chronology: do the right and the left testes migrate at the same time? Analysis of 164 human fetuses. AB - OBJECTIVE: To determine if the right and the left testes migrate at the same time during the human fetal period. SUBJECTS AND METHODS: We studied 164 human fetuses (328 testes) ranging in age from 12 to 35 weeks post-conception. The fetuses were carefully dissected with the aid of a stereoscopic lens at *16/25. The abdomen and pelvis were opened to identify and expose the urogenital organs. Testicular position was classified as: (a) Abdominal, when the testis was proximal to the internal ring; (b) Inguinal, when it was found between the internal and external inguinal rings); and (c) Scrotal, when it was inside the scrotum. RESULTS: The testes were abdominal in 71% of the cases, inguinal in 9.41%, and scrotal in 19.81%. There was asymmetry in testicular migration in nine cases (5.5%). In three of these nine cases, one testis was situated in the abdomen and the other in the inguinal canal; in another three one testis was situated in the abdomen and the other in the scrotum, and in the remaining three, one testis was in the inguinal canal and the other in the scrotum. In five of the nine cases of asymmetry, the right testis completed the migration first, but this was not statistically significant. CONCLUSION: Asymmetry in testicular migration is a rare event, accounting for <6% of the cases. The right testis seems to complete migration first. PMID- 24238430 TI - Phosphatidylglycerol homeostasis in glycerol-phosphate auxotrophs of Staphylococcus aureus. AB - BACKGROUND: The balanced synthesis of membrane phospholipids, fatty acids and cell wall constituents is a vital facet of bacterial physiology, but there is little known about the biochemical control points that coordinate these activities in Gram-positive bacteria. In Escherichia coli, the glycerol-phosphate acyltransferase (PlsB) plays a key role in coordinating fatty acid and phospholipid synthesis, but pathogens like Staphylococcus aureus have a different acyltransferase (PlsY), and the headgroup of the major membrane phospholipid, phosphatidylglycerol (PtdGro), is used as a precursor for lipoteichoic acid synthesis. RESULTS: The PlsY acyltransferase in S. aureus was switched off by depriving strain PDJ28 (DeltagpsA) of the required glycerol supplement. Removal of glycerol from the growth medium led to the rapid cessation of phospholipid synthesis. However, the continued utilization of the headgroup caused a reduction in PtdGro coupled with the accumulation of CDP-diacylglycerol and phosphatidic acid. PtdGro was further decreased by its stimulated conversion to cardiolipin. Although acyl-acyl carrier protein (ACP) and malonyl-CoA accumulated, fatty acid synthesis continued at a reduced level leading to the intracellular accumulation of unusually long-chain free fatty acids. CONCLUSIONS: The cessation of new phospholipid synthesis led to an imbalance in membrane compositional homeostasis. PtdGro biosynthesis was not coupled to headgroup turnover leading to the accumulation of pathway intermediates. The synthesis of cardiolipin significantly increased revealing a stress response to liberate glycerol-phosphate for PtdGro synthesis. Acyl-ACP accumulation correlated with a decrease in fatty acid synthesis; however, the coupling was not tight leading to the accumulation of intracellular fatty acids. PMID- 24238432 TI - Incidence of cholesterol in periapical biopsies among adolescent and elderly patients. AB - INTRODUCTION: Cholesterol clefts are common histologic findings in periapical biopsies; they have a reported incidence in periapical periodontitis of up to 44%. Cholesterol crystals are also recognized in advanced atherosclerotic plaques in humans. Male sex, genetic abnormalities, and age have been associated with advanced atherosclerotic lesions. Among these nonmodifiable risk factors, age is the most dominant. The aim of the study was to evaluate if age is also linked to cholesterol deposition in periapical periodontitis. METHODS: The database of biopsy reports obtained between 2006 and 2009 was searched for specimens diagnosed as radicular cysts or periapical granulomas. Only data relating to biopsies obtained from adolescent (13-21 years old) and elderly (over 60 years old) patients were selected. The biopsies were examined by a pathologist under a light microscope (Zeiss, Jena, Germany) at magnifications of 40*-200*. The available material was scanned for the presence of cholesterol clefts and foamy cells in radicular cysts and granulomas. RESULTS: A total of 41 specimens were collected in the adolescent group and 48 specimens in the elderly group over a 4 year period. A higher incidence of cholesterol was found in the elderly group compared with that in the adolescent group (odds ratio = 6.857). CONCLUSIONS: The highly significant incidence of cholesterol deposits in periapical biopsies among elderly patients may be a possible cause for the lack of repair. The mechanism for cholesterol accumulation is probably similar to the process leading to atherosclerosis and coronary artery disease. Statin administration may be advantageous for the treatment of persistent lesions. A clinician should be aware of the risk for persistent lesions after endodontic treatment in elderly patients. PMID- 24238433 TI - Rubber dam use during post placement influences the success of root canal-treated teeth. AB - INTRODUCTION: Salivary leakage after root canal therapy is of great concern and can lead to failure of the endodontic therapy. The aim of this study was to investigate whether the use of a rubber dam (RD) during post placement impacts the success of root canal-treated teeth. METHODS: Retrospective chart reviews of 185 patients with an average recall of 2.7 years were assessed for the incidence of a new periapical lesion (periapical index score >2) after root canal therapy and post placement. The patients were divided into 2 groups based on the presence or absence of an RD clamp in the verification radiograph during post placement. RESULTS: Twenty-six patients (30 teeth) had a post placed with the use of an RD, and 159 patients (174 teeth) had a post placed without an RD. In the non-RD group, 128 (73.6%) teeth were considered successful at follow-up. In the RD group, 28 (93.3%) teeth were considered successful at follow-up. Based on the bivariate GEE model, the difference in success between these 2 groups was statistically significant (P = .035). CONCLUSIONS: The use of an RD during prefabricated post placement provides a significantly higher success rate of root canal-treated teeth. Using an RD is already considered a standard of care for nonsurgical root canal therapy; in addition, using an RD during restorative procedures that involve open teeth should also become a standard of care. PMID- 24238434 TI - Evaluation of the reliability and accuracy of using cone-beam computed tomography for diagnosing periapical cysts from granulomas. AB - INTRODUCTION: The purpose of this study was to evaluate the reliability and accuracy of cone-beam computed tomographic (CBCT) imaging against the histopathologic diagnosis for the differential diagnosis of periapical cysts (cavitated lesions) from (solid) granulomas. METHODS: Thirty-six periapical lesions were imaged using CBCT scans. Apicoectomy surgeries were conducted for histopathological examination. Evaluator 1 examined each CBCT scan for the presence of 6 radiologic characteristics of a cyst (ie, location, periphery, shape, internal structure, effects on surrounding structure, and perforation of the cortical plate). Not every cyst showed all radiologic features (eg, not all cysts perforate the cortical plate). For the purpose of finding the minimum number of diagnostic criteria present in a scan to diagnose a lesion as a cyst, we conducted 6 receiver operating characteristic curve analyses comparing CBCT diagnoses with the histopathologic diagnosis. Two other independent evaluators examined the CBCT lesions. Statistical tests were conducted to examine the accuracy, inter-rater reliability, and intrarater reliability of CBCT images. RESULTS: Findings showed that a score of >=4 positive findings was the optimal scoring system. The accuracies of differential diagnoses of 3 evaluators were moderate (area under the curve = 0.76, 0.70, and 0.69 for evaluators 1, 2, and 3, respectively). The inter-rater agreement of the 3 evaluators was excellent (alpha = 0.87). The intrarater agreement was good to excellent (kappa = 0.71, 0.76, and 0.77). CONCLUSIONS: CBCT images can provide a moderately accurate diagnosis between cysts and granulomas. PMID- 24238435 TI - Prognostic factors of clinical outcomes in endodontic microsurgery: a prospective study. AB - INTRODUCTION: This prospective study examined the potential prognostic factors of endodontic microsurgery and compared the predictors of an isolated endodontic lesion with those of both an isolated endodontic lesion and an endodontic periodontal lesion. METHODS: Data were collected from the Microscope Center of the Department of Conservative Dentistry at the Dental College of Yonsei University, Seoul, Korea, between March 2001 and March 2011. A total number of 584 teeth were included, and all clinical procedures were performed by a single operator (E.K.). The evaluation was performed at least 1 year after surgery. For statistical analysis of the predisposing factors, the chi-square test and logistic regression were performed. RESULTS: Of the 584 cases treated, 431 cases came for recall after a period of at least 12 months. Sex (female), tooth position (anterior), arch type (maxilla), and lesion type (isolated endodontic lesion) were found to have a positive effect on surgical outcome. With regards to isolated endodontic lesions, the tooth position (anterior), arch type (maxilla), and type of restoration (single/splinted crown, short bridge, and removable partial denture abutment) were found to be pure positive predictors. CONCLUSIONS: In endodontic microsurgery, it is likely that preoperative factors, particularly the tooth position and arch type, have a greater influence on the healing outcome than intra- and post-operative factors. PMID- 24238436 TI - MicroRNAs: new insights into the pathogenesis of endodontic periapical disease. AB - INTRODUCTION: Apical periodontitis is an inflammatory disease of the periradicular tissues caused by the host's immune response to infection of the root canal system. MicroRNAs (miRNAs) have been shown to play an important role in the regulation of inflammation and the immune response; however, their role in the pathogenesis of endodontic periapical disease has not been explored. The purpose of this study was to examine the differential expression of miRNAs in diseased periapical tissues as compared with healthy controls. METHODS: We first compared miRNA profiles in diseased periapical tissues collected from patients undergoing endodontic surgery with those of healthy pulps by using microarray analyses. The target genes of the differentially expressed miRNAs were identified by using miRWalk and PubMed. Selected miRNAs linked to inflammation and the immune response were then confirmed in a separate cohort of diseased and healthy tissues by using quantitative reverse transcription-polymerase chain reaction. Healthy pulps and periodontal ligaments were used as controls. Data were normalized to the level of SNORD 44, which served as an endogenous control. RESULTS: Of the 381 miRNAs identified by using microarray, 24 miRNAs were down regulated in diseased periapical tissues compared with controls (n = 13) (P < .003). The down-regulation of 7 miRNAs was confirmed from 9 selected miRNAs by using quantitative real-time polymerase chain reaction (n = 19) (P < .05). Target genes of these miRNAs include key mediators in the immune and inflammatory response such as interleukin-6, matrix metalloproteinase-9, and transforming growth factor-beta. CONCLUSIONS: These findings offer new insight into the pathogenesis of endodontic disease and have the potential to impact the development of new methods for prevention, diagnosis, and treatment of apical periodontitis. PMID- 24238437 TI - Volumetric changes in apical radiolucencies of endodontically treated teeth assessed by cone-beam computed tomography 1 year after orthograde retreatment. AB - INTRODUCTION: Cone-beam computed tomography (CBCT) allows us to assess in 3 dimensions the location and size of periapical radiolucencies. We aimed to assess by CBCT scans the volumetric changes of periapical radiolucencies in endodontically treated teeth 1 year after orthograde retreatment. METHODS: Forty five root-filled teeth with persistent apical periodontitis requiring endodontic orthograde retreatment from 37 individuals were included in the study. The research protocol was approved by the VU University Medical Center Amsterdam ethics committee (2007/265), and the participants signed a letter of consent. We made 2 CBCT scans for every patient, the first one before retreatment and the second one a year later. Two observers measured independently the volume of radiolucencies on CBCT images by using the AMIRA software. The intraclass correlation coefficient was used to evaluate interobserver agreement, and the Wilcoxon signed rank test was used to assess pretreatment and post-treatment volume size. RESULTS: The intraclass correlation coefficients were 0.994 and 0.998 for the scans before retreatment and 1 year after, respectively. The recall rate was 78% for the teeth and 73% for the patients. The volumetric change in periapical radiolucencies 1 year after retreatment was statistically significant (z = -3.112, P < .005). The volume of periapical radiolucencies reduced in 20 teeth (57%), remained unchanged in 8 (23%), and increased in 7 (20%). CONCLUSIONS: One year after endodontic orthograde retreatment, the volume of periapical radiolucencies reduced significantly in 57% of the teeth. PMID- 24238438 TI - The dynamics of periapical lesions in endodontically treated teeth that are left without intervention: a longitudinal study. AB - INTRODUCTION: The long-term dynamics of periapical lesions in endodontically treated teeth is not fully elucidated, thus presenting a clinical dilemma regarding the need for an intervention. The aim of the study was to retrospectively evaluate the long-term dynamics of periapical lesions that were left without intervention in endodontically treated teeth. METHODS: Periapical status surveys of patients treated in a public dental clinic were retrospectively evaluated for the presence of periapical lesions in endodontically treated coronally restored teeth. The dynamics of the included periapical lesions was evaluated based on the periapical index (PAI) score changes between 2 consecutive periapical surveys of at least a 4-year interval. The influence of various factors on lesion dynamics was statistically evaluated. RESULTS: The study cohort consisted of 74 patients with a total of 200 endodontically treated teeth having periapical lesions that fulfilled the inclusion criteria. Fifty-seven (28.5%) lesions remained unchanged, 103 (51.5%) lesions worsened (PAI score increased), and 40 (20%) lesions improved (PAI score decreased). Poor root canal filling and poor restoration were found to adversely affect the long-term dynamics of the periapical lesions (P < .05). Age, sex, and the presence of a post had no statistically significant influence on lesion dynamics (P > .05). CONCLUSIONS: Poor root canal filling and poor restoration may adversely affect the long-term dynamics of periapical lesions that are left without intervention in endodontically treated teeth. Therefore, in cases of poor root canal filling or poor restoration, further intervention may be indicated. PMID- 24238439 TI - Morphology of mandibular first molars analyzed by cone-beam computed tomography in a Korean population: variations in the number of roots and canals. AB - INTRODUCTION: The aim of this study was to determine the root and canal morphology of the mandibular first molars in a Korean population of Mongolian origin by retrospective analysis of a large number of cone-beam computed tomography (CBCT) images. METHODS: A total of 976 subjects with bilateral mandibular first molars were examined by using in vivo CBCT methods. The number and configuration of roots, the number of root canals, and the canal configuration based on Vertucci's classification were determined. RESULTS: Overall, 25.82% of examined molars had 3 roots, 73.51% had 2 roots, and 0.67% had 1 root. The incidence of fourth canal was 50.36%. A right-sided predominance was noted for extra distal roots (P < .001), whereas a left-sided predominance was observed for extra distal canals (P < .001). No significant sex-related differences were shown for their prevalence. The bilateral prevalence rate was 69.13% for extra distal roots and 78.08% for extra distolingual (DL) canals. In the mesial roots, type IV canal was the most frequent (76.86% for 2-rooted molars and 72.96% for 3-rooted molars). In the distal roots, type l was the most common (66.62% for 2-rooted molars and 99.40%-100% for 3-rooted molars). The incidence of 2 canals in distobuccal roots, first reported in this study, was 0.15%. CONCLUSIONS: Among mandibular first molars, there is a high prevalence of a separate DL root and/or a separate DL canal, and such molars commonly have 4 canals in the Korean population. CBCT is a useful tool for determining root and canal morphology. PMID- 24238440 TI - Location and dimensions of the mental foramen: a radiographic analysis by using cone-beam computed tomography. AB - INTRODUCTION: The mental foramen (MF) is an important landmark in dentistry. Knowledge of its position is central to perform block anesthesia of the mental nerve or to avoid nerve damage during surgical procedures in the premolar area of the mandible. The present radiographic study aimed at evaluating the location and dimension of the MF and measuring distances to neighboring structures by using limited cone-beam computed tomography (CBCT). METHODS: Sagittal, axial, and coronal CBCT images of 142 patients (26 bilateral and 116 unilateral cases) were retrospectively screened to determine the location of the MF with respect to adjacent teeth and to take linear measurements of the size of the MF and its distances to the upper and lower borders of the mandible. In addition, the course and angulation of the mental canal exiting the MF were assessed. RESULTS: The majority of MF (56%) were located apically between the 2 premolars, and another 35.7% of MF were positioned below the second premolar. On average, the MF was localized 5.0 mm from the closest root of the adjacent tooth (range, 0.3-9.8 mm). The mean size of the MF showed a height of 3.0 mm and a length of 3.2 mm; however, individual cases showed large differences in height (1.8-5.1 mm) and in length (1.8-5.5 mm). All mental canals exiting the MF demonstrated an upward course in the coronal plane, with 70.1% of the mental canal presenting an anterior loop (AL) in the axial view. The mean extension of AL in cases with an AL was 2.3 mm. CONCLUSIONS: This study is consistent with previous radiographic studies regarding size and location of MF and distances between MF and adjacent anatomic structures. The assessed bilateral cases showed a high intraindividual concordance for certain features when comparing right and left sides. PMID- 24238441 TI - Micro-computed tomography analysis of the root canal anatomy and prevalence of oval canals in mandibular incisors. AB - INTRODUCTION: This study aimed to describe the anatomy of the mandibular incisors by using micro-computed tomography. METHODS: Mandibular incisors (n = 340) were scanned at 19-MUm voxel size resolution, and the numbers of canals were classified according to Vertucci classification, as well as the major and minor diameters of the root and root canals, presence of oval canals, and three dimensional analysis of the apical third were also measured. Data were presented in terms of median and range for each anatomic classification. RESULTS: Overall, the specimens had 1 root canal (N = 257). The second most prevalent anatomy was Vertucci type III (N = 56). These anatomies represent 92% of the sample. The medians of the major diameter at the 1-, 2-, and 3-mm level of the most prevalent anatomies were 0.36, 0.39, and 0.47 mm for type I and 0.41, 0.51, and 0.66 mm for type III, respectively. The apical volume appears to be constant among these anatomies (0.63 and 0.59 mm(3)). Oval canals were found at the 1-mm apical level, with a prevalence of 16.7% for Vertucci type I and 37.5% for Vertucci type III. The presence of oval canals increased at the 3-mm apical level to 32.4% and 76.2% for Vertucci type I and III classifications, respectively. CONCLUSIONS: Type I and III configurations represent 92% of the mandibular incisors studied. Within these anatomic configurations, oval-shaped canals in the apical third were not uncommon and more prevalent in the type III anatomy. PMID- 24238442 TI - A survey of patients' preferences for the treatment of teeth with apical periodontitis. AB - INTRODUCTION: This research aimed to investigate the preference of patients in Toronto, Canada for management of a tooth affected by painful apical periodontitis when considering its retention via root canal treatment (RCT) and its extraction followed by no replacement, replacement with an implant-supported crown, fixed, or removable partial prostheses. METHODS: Data were collected through a mail-out survey of the University of Toronto Faculty of Dentistry patients, which was complemented by a convenience sample of patients in 10 community practices in Toronto (n = 1000, response rate = 43%). Participants were asked to select their general preference for anterior and posterior teeth with apical periodontitis between saving the tooth or extraction and their specific preference for tooth retention via RCT or extraction. By using bivariate and logistic regression analyses, we applied the Gelberg-Andersen Behavioral Model for Vulnerable Populations to the preference questions to understand the influential factors (P <= .05). RESULTS: Participants' specific preference for tooth retention via RCT was slightly but significantly lower than their general preference (anterior tooth, 93.7% versus 97.2%; posterior tooth, 83.8% versus 89.6%; P < .005). Higher annual income, previous RCT, functional dentition, good/excellent self-rated oral health, and regular dental visits were associated with higher preferences for tooth retention in response to different questions. CONCLUSIONS: The high preference for retaining a tooth in general was moderated by the specific consideration of RCT to retain the tooth. When RCT and extraction are viable options, patients should be advised about the treatment options in an impartial manner and encouraged to communicate their preferences. PMID- 24238443 TI - Alveolar bone width preservation after decoronation of ankylosed anterior incisors. AB - INTRODUCTION: The aim of the study was to assess the alteration of alveolar ridge dimensions after decoronation procedures in children and adolescents at least 1 year after surgery. METHODS: Twelve children who underwent decoronation of ankylosed maxillary anterior incisors with at least 1 year after surgery follow up were recalled for reevaluation. All decoronations were performed when the ankylosed teeth were submerged 1-1.5 mm. During the recall appointment, impressions of the upper arch were obtained. The bucco-palatal alveolar dimensions of the decoronated teeth were measured on the cast at the mid mesiodistal distance from the missing tooth and were compared with the distance from the contralateral healthy incisor. RESULTS: Overall, 12 children (9 male and 3 female) were reevaluated up to 82 months after decoronation (mean, 49.58 +/- 24 months). The mean age of the patients at the time of trauma was 9.83 +/- 2.8 years. The average bucco-palatal dimension of the alveolar ridge at the mid decoronation area was 9 +/- 1 mm compared with 10.17 +/- 0.9 mm at the contralateral homologous tooth (difference of 1.67 +/- 1.12, P = .004). The findings show a positive statistical correlation between the duration of the follow-up period and the bucco-palatal dimension of the alveolar ridge (P = .027). CONCLUSIONS: Although decoronation of ankylosed young permanent incisors resulted in a decrease in the bucco-palatal dimension with time, it did not prevent additional alveolar growth that occurs with age in a developing child and thus may help maintain the alveolar bone ridge width, height, and continuity and assist in future rehabilitation with less invasive ridge augmentation procedures required for implant placement. PMID- 24238444 TI - Symmetry of root and root canal morphology of maxillary and mandibular molars in a white population: a cone-beam computed tomography study in vivo. AB - INTRODUCTION: The aim of the present study was to use cone-beam computed tomography (CBCT) to analyze root canal anatomy and symmetry of maxillary and mandibular first and second molar teeth of a white population. METHODS: A total of 201 patients who required CBCT examinations as part of their dental diagnosis and treatment were enrolled in the present study. Overall, 596 healthy, untreated, well-developed maxillary and mandibular molar teeth (161 maxillary first molars, 157 maxillary second molars, 117 mandibular first molars, and 161 mandibular second molars) were examined by CBCT to establish the symmetry in root and canal anatomy between right and left sides in the same patient by evaluating the number of roots and root canals and the root canal configuration. RESULTS: Three separate roots with 3 separate canals was the normal anatomy of maxillary first and second molars. Most mandibular first and second molars had 2 separate roots, and the majority had 3 canals. In the present study, first molars, both maxillary and mandibular, exhibited greater asymmetry than the second molars. Maxillary first molars were found to be symmetrical in 71.1% of patients, whereas maxillary second molars were symmetrical in 79.6%. The remaining 28.9% and 20.4% of patients, respectively, showed asymmetry. Around 30% of the mandibular first molars and 20% of the mandibular second molars showed asymmetry. CONCLUSIONS: The results of the present study reported a percentage of symmetry that varied from 70%-81%. These variations in symmetry should be taken in high consideration when treating 2 opposite molars in the same patient, because their anatomy may be different in up to 30% of the cases. PMID- 24238445 TI - Histologic characterization of engineered tissues in the canal space of closed apex teeth with apical periodontitis. AB - INTRODUCTION: The aim of this study was to investigate the capacity of endodontic regenerative procedures combining an induced blood clot, platelet-rich plasma (PRP), and bone marrow aspirate (BMA) to regenerate dental pulp in canine closed apex necrotic teeth. METHODS: Apical periodontitis was induced in 20 upper and lower premolars of 2 dogs. After biomechanical preparation, enlargement to a #60 file, and disinfection with a triantibiotic paste for 28 days, the roots were randomly assigned to 4 treatment groups: blood clot (BC), BC + PRP gel, BC + BMA gel, and BC + BMA/PRP gel. Negative controls were also included. After a 3-month follow-up period, the animals were killed. RESULTS: Histologic analysis showed the presence of newly formed vital tissues (connective, cement-like, and bone like tissue) in 23 of the 32 treated roots (71.87%). There was no statistically significant difference between the treatment groups. CONCLUSIONS: New vital tissues were formed and characterized as connective, cementum-like, or bone-like, but not as pulp-like tissue; PRP and/or BMA did not improve the tissue ingrowth. PMID- 24238446 TI - Antiosteoclastogenic activity of silicate-based materials antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine marcophages. AB - INTRODUCTION: This study investigated whether calcium silicate cement extract exerted antiosteoclastogenic actions in murine RAW 264.7 macrophages cultured with receptor activator for nuclear factor kappaB (RANKL). METHODS: The RAW 264.7 macrophage cell was treated with RANKL to osteoclastogenesis. Then, cell viability, cell death, and cathepsin K expression were examined. RESULTS: The silicon (Si)-inhibited RANKL-induced formation of osteoclasts during the osteoclast differentiation process. It was also found that >=4 mmol/L Si reduced RANKL-enhanced tartrate-resistant acid phosphatase (TRAP) activity in a dose dependent manner. Furthermore, Si diminished the expression and secretion of cathepsin K elevated by RANKL and was concurrent with the inhibition of TRAF6 induction and nuclear factor kappaB activation. CONCLUSIONS: The current report shows that silicate abrogated RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The Si can modulate every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, such as the proliferation and fusion of preosteoclasts, and the function of osteoclasts. Therefore, silicate-based materials may be a potential therapeutic agent targeting osteoclast differentiation in bone defects. PMID- 24238447 TI - Influence of 2 cryopreservation methods to induce CCL-13 from dental pulp cells. AB - INTRODUCTION: Cryopreservation preserves periodontal ligament cells but has a lower success rate with dental pulp cells (DPCs) because it causes inflammation. There are 2 well-known cryopreservation methods that reduce inflammation, slow freezing and rapid freezing, but the effects of the 2 methods on inflammation are not well-established. The purpose of this study was to compare the effects of the 2 different cryopreservation methods on CCL-13 induction from DPCs by using microarrays, real-time polymerase chain reaction (PCR), Western blotting, enzyme linked immunosorbent assay, and confocal laser scanning microscopy (CLSM). METHODS: In this study, the concentration of cryoprotectant was fixed, and the methods compared differed with respect to freezing speed. Initially we screened the DPCs of cryopreserved teeth with expression microarrays, and CCL-13 was identified as a differentially expressed gene involved in generalized inflammation. We then compared the expression of CCL-13 after exposing teeth to the 2 cryopreservation methods by using real-time PCR, Western blot, enzyme linked immunosorbent assay, and CLSM. RESULTS: Expression of CCL-13 was up regulated significantly only in the rapid freezing group, except in measurements made by real-time PCR. CLSM analysis also confirmed this up-regulation visually. CONCLUSIONS: Rapid freezing increased the expression of CCL-13 in DPCs compared with slow freezing. Understanding the inflammatory effect of cryopreservation should help to establish an optimal cryoprofile to minimize inflammation of DPCs and reduce the need for endodontic treatment. PMID- 24238448 TI - Leptin receptor is up-regulated in inflamed human dental pulp. AB - INTRODUCTION: After leptin receptor (LEPR) identification in hematopoietic, immune system, and other tissues, a role for leptin regulating inflammation and immune response has been accepted. This study aims to describe the possible expression of LEPR in healthy human dental pulp and to compare it with LEPR expression in inflamed human dental pulp. METHODS: Twenty-one pulp samples were obtained from freshly extracted caries-free and restoration-free human third molars. In 7 third molars (inflamed pulp group), inflammation was experimentally induced before extraction. Pulp samples were processed, and LEPR expression was determined by quantitative real-time polymerase chain reaction, and the amount of LEPR protein was analyzed by immunoblot. RESULTS: All healthy and inflamed dental pulp samples expressed LEPR. Western blot analysis of human dental pulp revealed the presence of a protein with an apparent molecular weight of approximately 120 kDa, which corresponds to the estimated molecular weight of LEPR. The expression of LEPR mRNA was confirmed by quantitative real-time polymerase chain reaction analysis, and the size of the amplified fragment (338 base pairs for LEPR and 194 base pairs for cyclophilin) was assessed by agarose gel electrophoresis. The relative amount of LEPR in inflamed pulps was approximately 50% higher than in healthy pulps (P < .05). CONCLUSIONS: The presence of LEPR in human dental pulp tissues has been demonstrated for the first time. The up-regulation of LEPR expression in inflamed pulp samples suggests that leptin can play a role in inflammatory and local immune responses in human dental pulp. PMID- 24238449 TI - Stress generation during self-adjusting file movement: minimally invasive instrumentation. AB - INTRODUCTION: Although nickel-titanium (NiTi) rotary instruments may produce a well- tapered root canal with a low tendency of aberrations, these are generally perceived to have a high fracture risk during use and may produce significant forces on root dentin during instrumentation, which may induce a dentinal defect or crack in the apical part of the root. This study compared mathematically the stress generated by the Self-Adjusting File (ReDent-Nova, Ra'anana, Israel) with conventional rotary instruments during the movement of 3 NiTi endodontic file designs in a curved root canal. METHODS: Stresses were calculated using finite element analysis. Three file designs with tip size ISO #20 were used in this study. Finite element models of ProFile #20/.06 (Dentsply Maillefer, Ballaigues, Switzerland) (a constant tapered shaft), ProTaper Universal F1 (Dentsply Maillefer) (a progressively changing taper shaft), and SAF 1.5 mm (a mesh shaft) were activated within a curved root canal model. The stress generations resulting from the simulated shaping movement were evaluated in the apical root dentin area. RESULTS: The SAF induced the lowest von Mises stress concentration and the lowest tensile principal stress component in root dentin. The calculated stress values from ProTaper Universal F1 and ProFile #20/.06 were approximately 8 to 10 times bigger than that of the SAF. CONCLUSIONS: Stress levels during shaping and the susceptibility to apical root cracks after shaping vary with instrument design. The design of the SAF may produce minimal stress concentrations in the apical root dentin during shaping of the curved canal, which may increase the chance of preservation of root dentin integrity with a reduced risk of dentinal defects and apical root cracking. PMID- 24238450 TI - The number of bleaching sessions influences pulp tissue damage in rat teeth. AB - INTRODUCTION: Hydrogen peroxide tooth bleaching is claimed to cause alterations in dental tissue structures. This study investigated the influence of the number of bleaching sessions on pulp tissue in rats. METHODS: Male Wistar rats were studied in 5 groups (groups 1S-5S) of 10 each, which differed by the number (1-5) of bleaching sessions. In each session, the animals were anesthetized, and 35% hydrogen peroxide gel was applied to 3 upper right molars. Two days after the experimental period, the animals were killed, and their jaws were processed for light microscope evaluation. Pulp tissue reactions were scored as follows: 1, no or few inflammatory cells and no reaction; 2, <25 cells and a mild reaction; 3, between 25 and 125 cells and a moderate reaction; and 4, 125 or more cells and a severe reaction. Results from each experimental group were compared between groups and within groups to the corresponding unbleached upper left molars and analyzed for significant differences using the Kruskal-Wallis test (P < .05). RESULTS: All tissue sections showed significant bleaching-induced changes in the dental pulp. After 1 bleaching session, necrotic tissue in the pulp horns and underlying inflammatory changes were observed. The extent and intensity of these changes increased with the number of bleaching sessions. After 5 sessions, the changes included necrotic areas in the pulp tissue involving the second third of the radicular pulp and intense inflammation in the apical third. CONCLUSIONS: The number of bleaching sessions directly influenced the extent of pulp damage. PMID- 24238451 TI - Evaluation of a new nickel-titanium system to create the glide path in root canal preparation of curved canals. AB - INTRODUCTION: Nickel-titanium rotary instruments recently have been introduced with the purpose of creating an initial glide path. The purpose of this study was to compare the maintenance of canal anatomy, the occurrence of apical transportation, and the working time observed using mechanised instrumentation with the new G-File rotary system (Micro-Mega, Besancon Cedex, France) with those observed using instrumentation with the PathFile system (Dentsply Maillefer, Ballaigues, Switzerland) and manual instrumentation with K-type files (Micro Mega) to create a glide path in curved root canals. METHODS: The mesial canals of 45 mandibular molars (with curvature angles between 25 degrees and 35 degrees ) were selected. The specimens were randomly divided into 3 groups with 15 canals each, and canal preparations were performed by an endodontist using #12-17 G-File rotary instruments (group GF), #13-16-19 PathFile rotary instruments (group PF), and #10-15-20 K-type stainless steel manual files (group M). A digital double radiographic technique was used to determine apical transportation and the change in the angle of curvature. The working time was also calculated. RESULTS: No statistically significant differences in the angle of canal curvature and apical transportation were found between the groups. However, concerning the working time, specimens from the group who underwent canal preparation using #12-17 G File rotary instruments achieved significantly lower mean values when compared with the other 2 groups, whereas the group who underwent canal preparation using the #10-15-20 K-type stainless steel manual files had the highest values. CONCLUSIONS: The G-File rotary instruments, the PathFile system, and the manual instruments did not have any influence on the occurrence of apical transportation nor did they produce a change in the angle of canal curvature. The G-File instruments seemed to be the most rapid system in creating a safe glide path. PMID- 24238452 TI - Cyclic fatigue resistance of K3, K3XF, and twisted file nickel-titanium files under continuous rotation or reciprocating motion. AB - INTRODUCTION: New designs and alloys and different motions have been introduced to increase the cyclic fatigue (CF) resistance of nickel-titanium (NiTi) files. The aim of this study was to compare the CF resistance of K3 (SybronEndo, Orange, CA), K3XF (SybronEndo), and TF (SybronEndo) files under continuous rotation and reciprocating motion. METHODS: A total of 210 files (30-tip diameter, 0.06 fixed taper), 60 K3, 60 K3XF, and 90 TF files, were divided into 7 groups (30 files each): K3-C, K3XF-C, and TF1-C were rotated at 300 rpm; TF2-C was rotated at 500 rpm; and K3-R, K3XF-R, and TF1-R were used in a reciprocating motion. CF resistance was tested in stainless steel, curved canals (60 degrees , r = 3 mm) until fracture, and the time to fracture was recorded. The mean half-life, beta, and eta were calculated for each group and were compared with Weibull analysis. RESULTS: The probability of a longer mean life was greater under reciprocating motion for all of the files (100% for K3, 87% for K3XF, and 99% for TF). Under continuous rotation, K3XF was more resistant than K3 and TF. TF lasted significantly longer than K3. TF was more resistant to CF when rotated at 300 rpm instead of 500 rpm. Under reciprocating motion, there were no significant differences between K3XF and TF mean lives, but both were significantly longer than the K3 mean life (78% for TF and 86% for K3XF). CONCLUSIONS: Reciprocating motion and R-phase increase CF resistance. PMID- 24238453 TI - Effect of agitation of EDTA with 808-nanometer diode laser on removal of smear layer. AB - INTRODUCTION: Near-infrared diode lasers can be used for several applications, which range from disinfection to smear layer removal in endodontics. This study evaluated the efficacy of agitation of 15% EDTA with an 808-nm diode laser on removal of the smear layer. METHODS: Sixty extracted human maxillary central incisor teeth were instrumented up to ProTaper F4 (Dentsply Maillefer, Ballagues, Switzerland) and then randomly divided into 6 groups (n = 10 for each group) according to the different final irrigating protocols as follows: 5% sodium hypochlorite for 120 seconds performed with the NaviTip (Dentsply Maillefer, Ballaigues, Switzerland) (control group); 15% EDTA for 120 seconds performed with the NaviTip; and agitation of 15% EDTA with an 808-nm diode laser for 10, 20, 30, and 40 seconds. Specimens were observed under a scanning electron microscope, and open dentinal tubules were counted using Adobe Photoshop software (Adobe Systems, San Jose, CA). The data were analyzed with 1-way analysis of variance and Tukey post hoc tests (P = .05). RESULTS: The number of open dentinal tubules was higher in the middle thirds than in the apical thirds. The differences between the apical and middle thirds were statistically significant (P < .05). Statistically significant differences were also found between the control group and the other groups in both the middle and apical thirds of the root canals (P < .05). CONCLUSIONS: The results indicated that agitation of 15% EDTA with an 808-nm diode laser for 20 seconds was effective in removing the smear layer in the apical thirds of root canals. PMID- 24238454 TI - Effect of torsional loading of nickel-titanium instruments on cyclic fatigue resistance. AB - INTRODUCTION: The aim of this study was to evaluate the effect of torsional preload on the cyclic fatigue life of nickel-titanium rotary instruments. METHODS: ProFile (#25/0.06) (Dentsply Maillefer, Ballaigues, Switzerland) and ProTaper (F1; Dentsply Maillefer) were used. Each file was preloaded at 4 conditions (ie, no preloading and 25%, 50%, and 75% of mean ultimate torsional strength) of torsional prestress before the fatigue test. The torsional preloads were applied by securing 5 mm of the file tip while keeping the file straight, rotating it clockwise until the preset torque, and then returning to the original position. This motion was repeated until a preset number (10, 30, or 50) of repetitions were reached (n = 12). After torsional preloading, the number of cycles to failure was evaluated in a simulated canal. Data were analyzed using 2 way analysis of variance and the Duncan post hoc comparison. The fractured fragment surfaces were examined under a scanning electron microscope for the topographic features of fractured instruments. RESULTS: For both instruments, there was a significant effect because of the extent of torsional preloads. The 50% and 75% torsionally preloaded ProFile and all ProTaper preloading groups had a higher number of cycles to failure than the other group(s). There was little difference in the lateral view appearance between new and torsionally preloaded files. After cyclic fatigue testing, all preloaded instruments showed numerous microcracks adjacent to the fracture site on lateral view examination. The microcracks did not seem to follow the machining grooves on the instrument surface but rather ran irregularly. CONCLUSIONS: The torsional preloads within the superelastic limit of the material may improve the cyclic fatigue resistance of nickel-titanium rotary instruments. PMID- 24238455 TI - Tooth discoloration after the use of new pozzolan cement (Endocem) and mineral trioxide aggregate and the effects of internal bleaching. AB - INTRODUCTION: The aim of this study was to evaluate tooth discoloration after the use of mineral trioxide aggregate (MTA) and to examine the effect of internal bleaching on discoloration associated with MTA. METHODS: Thirty-two teeth were endodontically treated. Three-millimeter plugs of MTA, ProRoot, Angelus, or Endocem were placed on the access cavities of 24 teeth. Eight teeth served as the control group. After 24 hours, the access cavities were restored, and the tooth color was recorded at baseline and at 1, 2, 4, 8, and 12 weeks. After 12 weeks, the MTA materials were removed under a microscope, and an internal bleaching treatment was performed. After removal of the MTA materials and after a 1-week bleaching treatment, the color changes were measured, and the MTA-dentin interfaces were observed under a microscope. RESULTS: The ProRoot and Angelus groups displayed increasing discoloration during a period of 12 weeks. The discoloration associated with ProRoot and Angelus was observed at the MTA-dentin interface and on the interior surface of the dentin. However, the Endocem groups demonstrated no significant discoloration (P < .05). No marginal discoloration was observed around the material in the Endocem group. Removal of the discolored MTA was effective for resolving the discoloration in all of the experimental groups (P < .05). However, a subsequent internal bleaching treatment was not significantly effective compared with the removal of MTA. CONCLUSIONS: ProRoot and Angelus caused tooth discoloration. However, Endocem did not affect the contacting dentin surface. Removing the discolored MTA materials contributed more to resolving the tooth discoloration than post-treatment internal bleaching. PMID- 24238456 TI - Evaluation of pH and calcium ion release of a dual-cure bisphenol A ethoxylate dimethacrylate/mineral trioxide aggregate-based root-end filling material. AB - INTRODUCTION: The incorporation of light-curable resins has been proposed for mineral trioxide aggregate (MTA) to improve its properties and reduce its setting time. The aim of the present study was to assess the pH and calcium ion release of an experimental bisphenol A ethoxylate dimethacrylate/MTA-based root-end filling material (E-MTA) in comparison with white MTA Angelus (Angelus, Londrina, PR, Brazil) (W-MTA) and to evaluate the influence of the addition of calcium chloride (CaCl2) on these properties. METHODS: Polyethylene tubes filled with the materials were immersed in deionized water for the measurement of pH (digital pH meter) and calcium release (atomic absorption spectrophotometry). The evaluations were performed at 3 and 24 hours and 7, 15, and 30 days. Data were measured using 2-way repeated measures of variance followed by the Holm-Sidak method (P < .05). RESULTS: All materials presented a reduction in the pH and released calcium ions during the 30 days of the study. E-MTA showed a significantly lower calcium ion release capacity when compared with W-MTA (P < .05). The calcium release of E-MTA + 5% CaCl2 was similar to W-MTA (P > .05). CONCLUSIONS: The monomer bisphenol A ethoxylate dimethacrylate added to MTA formed a material with a lower capacity of calcium release than W-MTA despite maintaining a similar pH. However, the addition of CaCl2 improved the calcium release of this material. PMID- 24238457 TI - The validity of cone-beam computed tomography in measuring root canal length using a gold standard. AB - INTRODUCTION: The distance between a coronal reference point and the major apical foramen is important for working length determination. The aim of this in vitro study was to determine the accuracy of root canal length measurements performed with cone-beam computed tomographic (CBCT) scans using a gold standard. METHODS: A total of 162 teeth (198 root canals) in 16 dry human dentulous mandibles were scanned using a 3DX-Accuitomo CBCT scanner (Morita 3DX; J Morita Mfg Corp, Kyoto, Japan). The root canal length was measured with CBCT data. All teeth were extracted atraumatically and endodontically accessed; the root canal length was measured blindly using a #10 K-file (Dentsply Maillefer, Ballaigues, Switzerland) and served as the gold standard. RESULTS: The mean absolute difference of the CBCT-based root canal length from the gold standard was 0.46 mm (95% confidence interval, 0.41-0.50 mm). Only in 9 of 198 (4.5%) roots did the difference between the CBCT-based root canal length and the gold standard exceed 1 mm. CONCLUSIONS: CBCT-based root canal length measurements are accurate and reliable when compared with a gold standard. PMID- 24238458 TI - Physical properties of AH Plus with chlorhexidine and cetrimide. AB - INTRODUCTION: The use of root canal filling materials with antibacterial activity could be considered beneficial to reduce any remaining microorganisms and prevent recurrent infection. The aim of this study was to evaluate the physical properties of AH Plus (Dentsply DeTrey, Konstanz, Germany) alone and mixed with 1% or 2% chlorhexidine (CHX); 0.1%, 0.2%, 0.3%, and 0.5% of cetrimide (CTR); and combinations of both. METHODS: Setting time, flow, solubility, and radiopacity of AH Plus and modified AH Plus were evaluated following the American National Standards Institute/American Dental Association's requirements (ANSI/ADA Specification No. 57/2000). Five samples of each material were tested for each property. The hypothesis of equality among groups was rejected by an analysis of variance test, and then a post hoc Tukey test was performed. RESULTS: AH Plus and modified AH Plus gave values that are within the required standards. Overall, results indicate that CTR increased setting time, but CHX alone and CHX + CTR reduced it. CHX increased the flow, whereas CTR reduced it, and their combinations gave intermediate values comparable with those of AH Plus. Concerning solubility, the weight loss in all samples was under the 3% limit set by the ANSI/ADA. In comparison with AH Plus alone, radiopacity gave slightly lower values with CHX, higher values with CTR, and similar values with combinations. CONCLUSIONS: The addition of CHX, CTR, and combinations of both to AH Plus did not alter the physical properties specified by ANSI/ADA requirements. PMID- 24238459 TI - In vitro assessment of torque and force generated by novel ProTaper Next Instruments during simulated canal preparation. AB - INTRODUCTION: The purpose of this study was to assess torque and force for simulated canal preparation with a new root canal instrument, ProTaper Next. METHODS: Six sets of ProTaper Next Instruments (X1-X5) were used to prepare 36 artificial canals. Files were divided into 6 groups. Different settings of rotations per minute (250, 300, and 350 rpm) and numbers of in-and-out movements to reach working length (3 or 4 insertions [ins]) were applied in each group (250 rpm/3 ins, 250 rpm/4 ins, 300 rpm/3 ins, 300 rpm/4 ins, 350 rpm/3 ins, and 350 rpm/4 ins) by using an automated torque bench. Peak torques (Ncm) as well as positive and negative forces (N) were registered. Analysis of variance and Tukey post hoc tests were applied. Preliminary data for angle and stationary torque at failure were also obtained and compared with peak torque for each instrument. RESULTS: Significant differences in peak torque (P < .0001), positive force (P < .002), and negative force (P < .0001) were found for ProTaper Next instruments overall. X2 showed the highest torque with all settings. X5 showed the highest positive force in all groups. X1 and X2 showed the highest negative forces for all groups except for 350 rpm/4 ins. Significantly lower torque (P < .0001) and positive force (P < .007) were measured in the group 350 rpm/4 ins for all instruments except for X4. In contrast, X1 showed a significantly lower negative force for 350 rpm/4 ins. Torque at failure according to American Dental Association no. 28/ISO 36030-1 was lower for X1, X2, and X3 than torque during simulated canal preparation (P < .0001). CONCLUSIONS: Under the conditions of this study, using ProTaper Next at 350 rpm and with 4 in-and-out movements resulted in lowest levels of peak torque as well as positive and negative forces. PMID- 24238460 TI - Detection of vertical root fractures in the presence of intracanal metallic post: a comparison between periapical radiography and cone-beam computed tomography. AB - INTRODUCTION: This in vitro study compared cone-beam computed tomography (CBCT) exam with different voxel sizes with digital periapical radiography in the detection of vertical root fractures in teeth with and without intracanal metallic posts. METHODS: Eighteen single-rooted human teeth were endodontically treated, prepared for cast metal posts, and artificially fractured. After positioning the teeth in dry mandibular sockets, the samples were subjected twice (with and without posts) to digital periapical radiography at 3 different angles and to CBCT examinations with 2 voxel sizes, 0.125 and 0.25 mm. The images were evaluated by 3 oral radiologists. Indices of sensitivity, specificity, and positive and negative predictive values, in addition to the areas under the receiver operating characteristic curves (accuracy), were calculated. Comparison of the accuracy of the imaging methods was assessed by using the chi(2) test. Comparison of the accuracy between teeth with and without posts was determined by using the Fisher exact test. RESULTS: The accuracy of the imaging methods showed no significant differences (P = .08). The comparison between teeth with and without posts in each examination revealed significant differences for CBCT with a voxel of 0.125 mm (P = .04) and for periapical radiography (P = .04). CONCLUSIONS: No significant differences were observed between CBCT and periapical radiography in the detection of vertical root fractures, except for teeth with metallic posts in images from CBCT with a voxel of 0.125 mm and in digital periapical radiography. Furthermore, voxel size did not significantly influence the diagnosis of vertical root fractures. PMID- 24238461 TI - Antibacterial efficacy of a human beta-defensin-3 peptide on multispecies biofilms. AB - INTRODUCTION: The aggregation of mixed bacterial flora into sessile biofilms on root canal surfaces can be one of the causes of persistent apical periodontitis. The aim of this study was to evaluate the antibacterial efficacy of human beta defensin-3 (HBD3) peptide on multispecies biofilms by using confocal laser scanning microscopy. METHODS: Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus mutans, and Enterococcus faecalis were cultured in a peptone-yeast glucose broth, and their culture suspensions were combined in equal proportions. The mixed bacteria were inoculated on sterile coverslips placed into the wells of tissue culture plates to permit the formation of mixed species biofilm. After incubation for 3 weeks, the samples were treated for 24 hours with saline (control), saturated calcium hydroxide solution (CH), 2% chlorhexidine solution (CHX), and 50 MUg/mL HBD3 solution. A commercial biofilm/viability assay kit was used to assess cell viability and analyze the 3-dimensional architecture of biofilms. The percentage of dead cells was determined from the ratio of biovolumes for the red subpopulation and the total biofilm. RESULTS: Three medication groups showed a significant reduction of biovolume within the biofilms compared with the control group (P < .001). The HBD3-treated biofilms had a higher percentage of dead cells than the other medication groups (P < .05). The CH and CHX groups showed higher levels of bactericidal activity than saline (P < .05), and there was no significant difference between the 2 groups (P > .05). CONCLUSIONS: HBD3 peptide exhibited more antibacterial activity against mature multispecies biofilms in vitro than either CH or CHX. PMID- 24238462 TI - In vitro fracture resistance of roots obturated with epoxy resin-based, mineral trioxide aggregate-based, and bioceramic root canal sealers. AB - INTRODUCTION: The aim of this study was to evaluate the fracture resistance of teeth filled with 3 different endodontic sealers. METHODS: Seventy-five single rooted extracted mandibular premolars were decoronated to a length of 13 mm. The teeth were randomly divided into 5 groups (n = 15 for each group). In group 1, the teeth were left unprepared and unfilled (negative control), and in group 2, the teeth were left unobturated (positive control). The rest of the roots were prepared by using the ProTaper System up to a master apical file size of F3: group 3, bioceramic sealer (Endosequence BC sealer) + gutta-percha; group 4, mineral trioxide aggregate-based sealer (Tech Biosealer Endo) + gutta-percha; and group 5, epoxy resin-based sealer (AH Plus Jet) + gutta-percha. All root specimens were stored for 2 weeks at 100% humidity to allow the complete setting of the sealers. Each specimen was then subjected to fracture testing by using a universal testing machine at a crosshead speed of 1.0 mm/min(-1) until the root fractured. The force required to fracture each specimen was recorded, and the data were analyzed statistically. RESULTS: The fracture values of groups 3 and 5 were significantly higher than those of group 4 (P < .05). There was no significant difference between groups 3 and 5 (P > .05). CONCLUSIONS: In contrast to Tech Biosealer Endo, Endosequence BC and AH Plus Jet sealer increased the force to fracture in root-filled single-rooted premolar teeth. PMID- 24238463 TI - Cutting efficiency of conventional and martensitic nickel-titanium instruments for coronal flaring. AB - INTRODUCTION: This study aimed at evaluating the influence of rotational speed and number of uses on the cutting efficiency of 4 nickel-titanium coronal flaring instruments against 2 substrates, bovine dentin and acrylic blocks. METHODS: BioRaCe BR0, HyFlex CM1, ProFile OS#2, and ProTaper Sx were used in simulated lateral action against both substrates at 250 and 500 rpm up to 5 times, producing 5 notches in each block. Notch areas and lengths were measured under a stereomicroscope, and data were compared by using parametric tests (alpha = 0.05). RESULTS: Against both substrates, HyFlex CM1 and ProFile OS#2 were the most and the least cutting efficient instruments, respectively (P < .05). Against acrylic, area and length values at 500 rpm were significantly higher than those at 250 rpm for all brands. Against dentin, significant differences were detected between 250 and 500 rpm for HyFlex CM1 and ProTaper Sx (area) and for BioRace BR0, HyFlex CM1, and ProTaper Sx (length). Regarding cutting efficiency loss, area and length for notches 1 and 2 (first notches) and 4 and 5 (last notches) were similar against acrylic. Against dentin, length values for notches 1 and 2 were significantly higher than those for notches 4 and 5 in ProFile OS#2 and ProTaper Sx. A strong correlation was detected between the overall results obtained on acrylic and dentin for area and length (P < .0001), although further analysis showed that data against acrylic were a poor predictor of data against dentin after repeated use. CONCLUSIONS: HyFlex CM1 was the most cutting efficient instrument in lateral action. An increase in rotational speed improved the cutting efficiency. Results against acrylic showed a high correlation to data against dentin, but acrylic may not be a proper substrate when the intention is to assess cutting efficiency loss with repeated use. PMID- 24238464 TI - Clinically relevant dimensions of 3-rooted maxillary premolars obtained via high resolution computed tomography. AB - INTRODUCTION: This study aimed to characterize the dimensions of a selection of 3 rooted maxillary premolars through high-resolution computed tomographic analysis considering measures of clinical interest for root canal treatment, such as root wall thickness, canal diameters, and distances between 2 canals in fused roots and between the root apex and foramen. METHODS: Fifteen 3-rooted human maxillary premolars extracted for therapeutic reasons were individually scanned using a high-resolution desktop high-resolution computed tomographic system. Starting from the apical foramen, the selected cross-sectional images corresponding to each millimeter of the roots were evaluated. Measures of clinical interest were determined using Image J software (version 1.41; National Institutes of Health, Bethesda, MD). RESULTS: Root wall thickness as thin as 0.4 and 0.6 mm was detected in the apical portion of buccal and palatal roots, respectively. In the cervical portion, buccal roots had narrower root walls (0.817-1.670 mm) compared with palatal roots (1.361-2.720 mm). In all thirds, the palatal canal was wider compared with the mesiobuccal and distobuccal canals. In the buccopalatal direction, all roots had thicker root walls toward the furcation, whereas in the mesiodistal direction the mesiobuccal and distobuccal roots had the thinnest walls along their distal and mesial aspects, respectively. Both buccal canals revealed dentin apposition 2 mm from the canal orifice, resulting in cervical constriction. Generally, the distance between the root apex and the foramen was greater in distobuccal roots in comparison with the others with a tendency for foramina to be eccentric. CONCLUSIONS: Three-rooted premolars are a clinical challenge not just because of their low frequency and difficulties regarding diagnosis and root canals access but also because of their fragile roots. These phenomena are critical in terms of the amount of dentin removed during the preparation of root canals and during post space preparation. PMID- 24238465 TI - Effect of acid etching procedures on the compressive strength of 4 calcium silicate-based endodontic cements. AB - INTRODUCTION: The purpose of this study was to evaluate the effect of acid etching on the compressive strength of 4 calcium silicate-based cements. METHODS: One gram of each corresponding powder of ProRoot MTA (Dentsply Tulsa Dental, Johnson City, TN), MTA Angelus (Angelus, Londrina, PR, Brazil), and CEM cement (BioniqueDent, Tehran, Iran) and a 0.33-g aliquot of liquid were placed in a plastic mixing capsule that was then mechanically mixed for 30 seconds at 4500 rpm in an amalgamator. For the preparation of Biodentine (Septodont, Saint Maur des-Fosses, France), the liquid provided was added to the powder within the plastic capsule supplied by the manufacturer and then mechanically mixed for 30 seconds at 4500 rpm using the amalgamator. The resulting slurries were then placed incrementally into 40 cylindrical molds to give a total of 160 specimens that were incubated at 37 degrees C for a week. Twenty specimens of each material were then subjected to the acid etch procedure. The compressive strength of the samples was then calculated in megapascals using a universal testing machine. The results were then subjected to 2-way analysis of variance analysis of variance followed by the Tukey post hoc test. RESULTS: The application of acid etch significantly reduced (P < .0001) the compressive strength of Angelus MTA and CEM cement; however, it did not reduce the compressive strength of ProRoot MTA or Biodentine. Regardless of the acid etch application, Biodentine showed significantly higher compressive strength values than the other materials (P < .0001), whereas CEM cement had the lowest compressive strength values. There was no significant difference between CEM cement and MTA Angelus. The compressive strength of ProRoot MTA was significantly lower (P < .0001) than Biodentine but significantly higher (P < .0001) than MTA Angelus and CEM cement in both the test and control groups. CONCLUSIONS: When the application of acid etchants is required, Biodentine and ProRoot MTA seem to be better options than MTA Angelus or CEM cement. PMID- 24238466 TI - C-shaped maxillary permanent first molar: a case report and literature review. AB - INTRODUCTION: The C-shaped configuration is rare in the upper first molar.The purpose of this article is to present 2 cases diagnosed during endodontic therapy and perform a literature review of this anatomy in the upper first molar. METHODS: Endodontic therapy was performed by using a dental operating microscope and a cone-beam computed tomography analysis for better understanding of this anatomy. A literature search was conducted to identify and compare all the published cases of C-shaped upper first molar. RESULTS: Before the cases reported in this article, only 5 cases were available in the published literature. Three different types of C-shaped configurations in the upper first molar have been presented. CONCLUSIONS: The C-shaped maxillary first molar is a rare anatomic configuration. The use of the dental operating microscope may help in the endodontic therapy of these cases. Three types of C-shaped configurations have been reported; the fusion of the distobuccal root with the palatal root appears to be the most usual one. PMID- 24238467 TI - Concomitant horner and harlequin syndromes after inferior alveolar nerve block anesthesia. AB - INTRODUCTION: Intraoral anesthesia is probably the most commonly used procedure in dentistry. METHODS: Although inferior alveolar nerve block (IANB) anesthesia is one of the safest procedures to anesthetize the mandibular teeth, side effects of IANB anesthesia can still give rise to potential risks for patients. Fortunately, most observed alterations are transient and self-limited. RESULTS: The complications of IANB anesthesia are varied in nature and could be specifically categorized into systemic, localized, and distant complications. When the complications occur around the orofacial structures including the temporomandibular joint, middle ear, facial skin, and the eye, which are away from the oral cavity, it can be defined as distant complications. However, to our best knowledge, the concomitant occurrence of neurologic phenomena such as Horner syndrome combined with cutaneous complications in a patient receiving IANB anesthesia has never been discussed. CONCLUSIONS: In this exceptional case, the unusual Horner syndrome manifestations related to unilateral ptosis, miosis, and anisocoria were simultaneously developed with skin ischemia, paresthesia, and asymmetric flushing after the administration of IANB anesthesia. PMID- 24238468 TI - Novel management of avulsed tooth by pulpal and periodontal regeneration. AB - INTRODUCTION: The avulsion of anterior teeth of young children is a tragic occurrence and often presents an unparalleled challenge for the dentist. Reimplantation is the state-of-the-art treatment but may incur several complications, particularly with inappropriate posttraumatic management. METHODS: In this article we report the emergency and rehabilitation treatment of an avulsed maxillary anterior tooth by using platelet-rich fibrin. The osteoconductive and osteoinductive properties of platelet-rich fibrin were used to stimulate pulpal and periodontal regeneration. RESULTS: During follow-up, no clinical signs and symptoms were present. After the initial 6 months, no further bone loss and attachment loss were observed. The tooth remained functional and was aesthetically acceptable. CONCLUSIONS: When a tooth is avulsed, attachment damage and pulp necrosis occur. Viable periodontal ligament cells are often left on most of the root surface. If the periodontal ligament that is left attached to the root surface does not dry out, the consequences of tooth avulsion are usually minimal. PMID- 24238470 TI - Group therapy for people with bulimia nervosa: systematic review and meta analysis. AB - BACKGROUND: Approximately 25% of people with bulimia nervosa (BN) who undertake therapy are treated in groups. National guidelines do not discriminate between group and individual therapy, yet each has potential advantages and disadvantages and it is unclear how their effects compare. We therefore evaluated how group therapy for BN compares with individual therapy, no treatment, or other therapies, in terms of remission from binges and binge frequency. METHOD: We performed a systematic review and meta-analysis of randomized controlled trials of group therapies for BN, following standard guidelines. RESULTS: A total of 10 studies were included. Studies were generally small with unclear risk of bias. There was low-quality evidence of a clinically relevant advantage for group cognitive behavioural therapy (CBT) over no treatment at therapy end. Remission was more likely with group CBT versus no treatment [relative risk (RR) 0.77, 95% confidence interval (CI) 0.62-0.96]. Mean weekly binges were lower with group CBT versus no treatment (2.9 v. 6.9, standardized mean difference = -0.56, 95% CI 0.96 to -0.15). One study provided low-quality evidence that group CBT was inferior compared with individual CBT to a clinically relevant degree for remission at therapy end (RR 1.24, 95% CI 1.03-1.50); there was insufficient evidence regarding frequency of binges. CONCLUSIONS: Conclusions could only be reached for CBT. Low-quality evidence suggests that group CBT is effective compared with no treatment, but there was insufficient or very limited evidence about how group and individual CBT compared. The risk of bias and imprecise estimates of effect invite further research to refine and increase confidence in these findings. PMID- 24238469 TI - Predictors of the resumption of menses in adolescent anorexia nervosa. AB - BACKGROUND: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. METHODS: A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. RESULTS: Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. CONCLUSIONS: The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies. PMID- 24238471 TI - Impact of age and obstacles on navigation precision and reaction time during blind navigation in dual-task conditions. AB - Navigation without vision is a skill that is often employed in our daily lives, such as walking in the dark at night. Navigating without vision to a remembered target has previously been studied. However, little is known about the impact of age or obstacles on the attentional demands of a blind navigation task. This study examined the impacts of age and obstacles on reaction time (RT) and navigation precision during blind navigation in dual-task conditions. The aims were to determine the effects of age, obstacles, and auditory stimulus location on RT and navigation precision in a blind navigation task. Ten healthy young adults (24.5+/-2.5 years) and ten healthy older adults (69.5+/-2.9 years) participated in the study. Participants were asked to walk to a target located 8m ahead. In half the trials, the path was obstructed with hanging obstacles. Participants performed this task in the absence of vision, while executing a discrete RT task. Results demonstrated that older adults presented increased RT, linear distance travelled (LDT), and obstacle contact; that obstacle presence significantly increased RT compared to trials with no obstacles; and that an auditory stimulus emitted early versus late in the path increased LDT. Results suggest that the attentional demands of blind navigation are higher in older than young adults, as well as when obstacles are present. Furthermore, navigation precision is affected by age and when participants are distracted by the secondary task early in navigation, presumably because the secondary task interferes with path estimation. PMID- 24238472 TI - Vitamin D deficiency in type 2 diabetic patients with hypogonadism. AB - INTRODUCTION: Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. AIM: The aim of this study was to evaluate 25 hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. METHODS: We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. MAIN OUTCOME MEASURES: Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. RESULTS: The overall diabetic population showed a mean 25(OH)D concentration (22.3 +/- 6.09 ng/mL) significantly lower than the control group (34.3 +/- 7.2, P < 0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (<20 ng/mL) or insufficiency (20 29.9 ng/mL). The lowest 25(OH)D concentration was found in Group 1 (20.1 +/- 6.58 ng/mL). Concentration of 25(OH)D was significantly lower in the 42 patients with hypogonadotropic hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 +/- 7.06 vs. 23.8 +/- 6.11 ng/mL, P < 0.001). No difference in erectile dysfunction (ED) prevalence between Group 1 and Group 2 was found, nor was there a correlation between the severity of ED and vitamin D levels (r = -0.10, P = 0.39). CONCLUSIONS: These results show that type 2 diabetic patients with hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study. PMID- 24238474 TI - Lymphomatoid papulosis presenting as periarticular nodules - a rare variant. PMID- 24238473 TI - Analysis of the contribution of immunologically-detectable HER2, steroid receptors and of the "triple-negative" tumor status to disease-free and overall survival of women with epithelial ovarian cancer. AB - We assessed associations between steroid receptors including: estrogen-alpha, estrogen-beta, androgen receptor, progesterone receptor, the HER2 status and triple-negative epithelial ovarian cancer (ERalpha-/PR-/HER2-; TNEOC) status and survival in women with epithelial ovarian cancer. The study included 152 women with primary epithelial ovarian cancer. The status of steroid receptor and HER2 was determined by immunohistochemistry. Disease-free and overall survival were calculated and compared with steroid receptor and HER2 status as well as clinicopathological features using the Cox Proportional Hazards model. A mean follow-up period of 43.6 months (interquartile range=41.4 months) was achieved where 44% of patients had serous tumor, followed by mucinous (23%), endometrioid (9%), mixed (9%), undifferentiated (8.5%) and clear cell tumors (5.3%). ER-alpha staining was associated with grade II-III tumors. Progesterone receptor staining was positively associated with a Body Mass Index>=25. Androgen receptor positivity was higher in serous tumors. In stand-alone analysis of receptor contribution to survival, estrogen-alpha positivity was associated with greater disease-free survival. However, there was no significant association between steroid receptor expression, HER2 status, or TNEOC status, and overall survival. Although estrogen-alpha, androgen receptor, progesterone receptor and the HER2 status were associated with key clinical features of the women and pathological characteristics of the tumors, these associations were not implicated in survival. Interestingly, women with TNEOC seem to fare the same way as their counterparts with non-TNEOC. PMID- 24238475 TI - Toward 3D graphene oxide gels based adsorbents for high-efficient water treatment via the promotion of biopolymers. AB - Recent studies showed that graphene oxide (GO) presented high adsorption capacities to various water contaminants. However, the needed centrifugation after adsorption and the potential biological toxicity of GO restricted its applications in wastewater treatment. In this study, a facile method is provided by using biopolymers to mediate and synthesize 3D GO based gels. The obtained hybrid gels present well-defined and interconnected 3D porous network, which allows the adsorbate molecules to diffuse easily into the adsorbent. The adsorption experiments indicate that the obtained porous GO-biopolymer gels can efficiently remove cationic dyes and heavy metal ions from wastewater. Methylene blue (MB) and methyl violet (MV), two cationic dyes, are chosen as model adsorbates to investigate the adsorption capability and desorption ratio; meanwhile, the influence of contacting time, initial concentration, and pH value on the adsorption capacity of the prepared GO-biopolymer gels are also studied. The GO-biopolymer gels displayed an adsorption capacity as high as 1100 mg/g for MB dye and 1350 mg/g for MV dye, respectively. Furthermore, the adsorption kinetics and isotherms of the MB were studied in details. The experimental data of MB adsorption fitted well with the pseudo-second-order kinetic model and the Langmuir isotherm, and the results indicated that the adsorption process was controlled by the intraparticle diffusion. Moreover, the adsorption data revealed that the porous GO-biopolymer gels showed good selective adsorbability to cationic dyes and metal ions. PMID- 24238476 TI - Organophosphorus pesticide and ester analysis by using comprehensive two dimensional gas chromatography with flame photometric detection. AB - Thirty-seven phosphorus (P)-containing compounds comprising organophosphorus pesticides and organophosphate esters were analyzed by using comprehensive two dimensional gas chromatography with flame photometric detection in P mode (GC * GC-FPD(P)), with a non-polar/moderately polar column set. A suitable modulation temperature and period was chosen based on experimental observation. A number of co-eluting peak pairs on the (1)D column were well separated in 2D space. Excellent FPD(P) detection selectivity, responding to compounds containing the P atom, produces clear 2D GC * GC plots with little interference from complex hydrocarbon matrices. Limits of detection (LOD) were within the range of 0.0021 0.048 MUmol L(-1), and linear calibration correlation coefficients (R(2)) for all 37 P-compounds were at least 0.998. The P-compounds were spiked in 2% diesel and good reproducibility for their response areas and retention times was obtained. Spiked recoveries were 88%-157% for 5 MUg L(-1) and 80%-138% for 10 MUg L(-1) spiked levels. Both (1)tR and (2)tR shifts were noted when the content of diesel was in excess of 5% in the matrix. Soil samples were analyzed by using the developed method; some P-compounds were positively detected. In general, this study shows that GC * GC-FPD(P) is an accurate, sensitive and simple method for P compound analysis in complicated environmental samples. PMID- 24238478 TI - Why we need narratives of healing and qualitative pain research. PMID- 24238479 TI - Healthcare expenses associated with multiple vs singleton pregnancies in the United States. AB - OBJECTIVE: The purpose of this study was to document cost that is associated with multiple births vs singleton births in the United States. STUDY DESIGN: This was a retrospective cohort study that used a claims database. Women 19-45 years old with live-born infants from 2005-2010 were identified. Infant deliveries were identified by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. The cost entailed all payment made by insurers and patients. For mothers, the cost included expenses from 27 weeks before delivery to 1 month after delivery. For infants, the cost contained all expenses until their first birthday. Adjusted cost was estimated by generalized linear models after adjustment for the potential confounding variables with a gamma distribution and a log link. RESULTS: The analysis included 437,924 eligible deliveries. Of them, 97.02% were singletons; 2.85% were twins, and 0.13% was triplets or more. Women with multiple pregnancies had higher systemic and localized comorbidities compared with women with singleton pregnancies (P < .0001). Twins and triplets or more were more likely to have stayed in a neonatal intensive care unit than were singletons (P < .0001). On average, adjusted total all-cause health care cost was $21,458 (95% confidence interval [CI], $21,302 21,614) per delivery with singletons, $104,831 (95% CI, $103,402-106,280) with twins, and $407,199 (95% CI, $384,984-430,695) with triplets or more. CONCLUSION: Pregnancies with the delivery of twins cost approximately 5 times as much when compared with singleton pregnancies; pregnancies with delivery of triplets or more cost nearly 20 times as much. PMID- 24238477 TI - Clinical review: Lung imaging in acute respiratory distress syndrome patients--an update. AB - Over the past 30 years lung imaging has greatly contributed to the current understanding of the pathophysiology and the management of acute respiratory distress syndrome (ARDS). In the past few years, in addition to chest X-ray and lung computed tomography, newer functional lung imaging techniques, such as lung ultrasound, positron emission tomography, electrical impedance tomography and magnetic resonance, have been gaining a role as diagnostic tools to optimize lung assessment and ventilator management in ARDS patients. Here we provide an updated clinical review of lung imaging in ARDS over the past few years to offer an overview of the literature on the available imaging techniques from a clinical perspective. PMID- 24238480 TI - Type 2 Brugada pattern is suggestive but not diagnostic of the syndrome. PMID- 24238481 TI - Rapid spontaneous recovery after development of a spinal epidural hematoma: a case report. AB - Spontaneous spinal epidural hematoma is a very rare clinical emergency. A permanent neurological deficit or even death may result if diagnosis and treatment are delayed. Many cases can be diagnosed upon detailed neurological examination and magnetic resonance (MR) imaging. Usually, surgery is required, but rarely, the condition may improve spontaneously. A 46-year-old male patient was admitted to our emergency department because of rapidly evolving severe paraplegia following development of sudden-onset neck pain. Spinal MR imaging detected an epidural hematoma compressing the spinal cord at the C5-T1 level. Clinical and radiological follow-up showed that the patient recovered spontaneously in 48 hours without any need for surgical treatment. PMID- 24238482 TI - Voltage attenuation of the electrocardiogram in Takotsubo syndrome: what ED physicians should consider. PMID- 24238483 TI - Antibiotics for methicillin-resistant Staphylococcus aureus skin and soft tissue infections: the challenge of outpatient therapy. AB - PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming increasingly prevalent in both community and hospital settings. Certain strains are notorious for causing skin and soft tissue infections in patients with no established risk factors. In this article, we report our findings on the dynamic antibiotic resistance pattern of MRSA and outpatient prescription trend for skin and soft tissue infections within our community. METHODS: We conducted a retrospective medical record review of 1876 patients evaluated in the emergency department of an urban community hospital from 2003 to 2012. Data regarding culture isolates and associated antimicrobial resistance, antibiotic treatment, site of specimen collection, age, race, and sex were collected and analyzed. RESULTS: Analysis of 1879 culture specimens yielded 2193 isolates. In some cases, a single specimen yielded polymicrobial growth. Staphylococcus aureus represented 996 isolates (45.4%); 463 were methicillin-susceptible (21.1%) and 533 (24.3%) were methicillin-resistant. Most patients were prescribed a single- or poly-drug regimen of trimethoprim/sulfamethoxazole, cephalexin, and clindamycin. Antimicrobial resistance analysis indicated that MRSA became increasingly resistant to the aforementioned antibiotics over time: 10% and 6% in 2012 vs 3.5% and 3.4% in 2007 for clindamycin and trimethoprim/sulfamethoxazole, respectively. CONCLUSION: Methicillin-resistant Staphylococcus aureus is a particularly virulent, rapidly adaptive pathogen that is becoming increasingly difficult to combat with existing antibiotics. Care must be taken to ensure appropriate treatment and follow-up of patients with known MRSA infections. PMID- 24238484 TI - Addition of glucagon to adrenaline improves hemodynamics in a porcine model of prolonged ventricular fibrillation. AB - OBJECTIVE: Cardiac arrest is a daunting medical emergency. The aim of the present study was to assess whether the combination of adrenaline and glucagon would improve initial resuscitation success, 48-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. METHODS: Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets, which were subsequently left untreated for 8 minutes. The animals were randomized to receive adrenaline alone (n = 10, group C) and adrenaline plus glucagon (n = 10, group G). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Hemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 60 minutes after return of spontaneous circulation. Survival and a neurologic alertness score were measured at 48 hours after return of spontaneous circulation. RESULTS: Return of spontaneous circulation was achieved in 8 animals (80%) from group C and 10 animals (100%) from group G (P = .198). A significant gradual increase in coronary perfusion pressure and diastolic aortic pressure over time, which started 1 minute after the onset of cardiopulmonary resuscitation, was observed. Three animals (30%) from group C and 9 animals (90%) from group G survived after 48 hours (P = .006), whereas neurologic examination was significantly better in the animals of group G (P < .001). CONCLUSIONS: In this porcine model of prolonged ventricular fibrillation, the addition of glucagon to adrenaline improves hemodynamics during resuscitation and early postresuscitation period and may increase survival. PMID- 24238485 TI - The new Vancouver Chest Pain Rule using troponin as the only biomarker: an external validation study. AB - OBJECTIVES: To externally evaluate the accuracy of the new Vancouver Chest Pain Rule and to assess the diagnostic accuracy using either sensitive or highly sensitive troponin assays. METHODS: Prospectively collected data from 2 emergency departments (EDs) in Australia and New Zealand were analysed. Based on the new Vancouver Chest Pain Rule, low-risk patients were identified using electrocardiogram results, cardiac history, nitrate use, age, pain characteristics and troponin results at 2 hours after presentation. The primary outcome was 30-day diagnosis of acute coronary syndrome (ACS), including acute myocardial infarction, and unstable angina. Sensitivity, specificity, positive predictive values and negative predictive values were calculated to assess the accuracy of the new Vancouver Chest Pain Rule using either sensitive or highly sensitive troponin assay results. RESULTS: Of the 1635 patients, 20.4% had an ACS diagnosis at 30 days. Using the highly sensitive troponin assay, 212 (13.0%) patients were eligible for early discharge with 3 patients (1.4%) diagnosed with ACS. Sensitivity was 99.1% (95% CI 97.4-99.7), specificity was 16.1 (95% CI 14.2 18.2), positive predictive values was 23.3 (95% CI 21.1-25.5) and negative predictive values was 98.6 (95% CI 95.9-99.5). The diagnostic accuracy of the rule was similar using the sensitive troponin assay. CONCLUSIONS: The new Vancouver Chest Pain Rule should be used for the identification of low risk patients presenting to EDs with symptoms of possible ACS, and will reduce the proportion of patients requiring lengthy assessment; however we recommend further outpatient investigation for coronary artery disease in patients identified as low risk. PMID- 24238486 TI - Hiatal hernia squeezing the heart to flutter. AB - An 80-year-old woman presented to the emergency department with failure to thrive and weakness for 14 days. Medical history was significant for polio. On admission her electrocardiogram showed atrial flutter, and cardiac enzymes were elevated. Echocardiogram revealed a high pulmonary artery pressure, but no other wall motion abnormalities or valvulopathies. Chest x-ray showed a large lucency likely representing a diaphragmatic hernia. Computed tomographic scan confirmed the hernia. Our patient remained in atrial flutter despite rate control, and thereafter surgery was consulted to evaluate the patient. She underwent hernia repair. After surgery, the patient was taken off rate control and monitored for 72 hours; she did not have any episode of atrial flutter and was discharged with follow up in a week showing no arrhythmia. Her flutter was caused directly by the mechanical effect of the large hiatal hernia pressing against her heart, as the flutter resolved after the operation. PMID- 24238487 TI - Safe Haven Laws: lack of awareness, misinformation, and shortfalls in resident education. PMID- 24238488 TI - Relation of uric acid and contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention in the ED. AB - OBJECTIVES: To investigate the predictive role of serum uric acid (SUA) levels measured in the emergency department (ED) to monitor contrast-induced nephropathy (CIN) and correlation with severity of nephropathy in patients undergoing primary percutaneous coronary intervention (PCI). METHOD: The patients who were admitted to our ED and underwent primary PCI were enrolled retrospectively. Their baseline characteristics including SUA and creatinine levels in the ED and their creatinine levels 48 hours after PCI were noted. Nephropathy was graded as follows: grade 0, DeltaCr <=25% and <=0.5 mg/dL; grade 1, DeltaCr >25% but <=0.5 mg/dL; and grade 2, DeltaCr >0.5 mg/dL. A multiple logistic regression analysis was used to define the independent predictors of CIN. RESULTS: Of a total of 744 patients, CIN was observed in 12.5% (n = 93). Serum uric acid levels were significantly higher in the CIN (+) group compared with the CIN (-) group (6.09 +/- 2.01 mg/dL vs 4.89 +/- 1.32 mg/dL, respectively; P < .001). Patients with grade 0 CIN had significantly lower SUA levels than did those with grades 1 and 2 (4.89 +/- 1.32 mg/dL vs 5.88 +/- 1.99 and 6.41 +/- 2.02 mg/dL, respectively; P < .001), but there was no significant difference between grade 1 and grade 2 CIN cases in terms of SUA levels (5.88 +/- 1.99 mg/dL vs 6.41 +/- 2.02 mg/dL, P = .10). The cutoff value for SUA was 5.05 mg/dL for the prediction of CIN (area under the curve, 0.685; P < .001; sensitivity, 66%; specificity, 60%) in the population. CONCLUSIONS: The SUA level is a simple independent early predictor of CIN in patients who underwent primary PCI, and early detection may help prevent the progression of CIN. PMID- 24238489 TI - Utilizing left ventricular outflow tract velocity changes to predict fluid responsiveness in septic patients: a case report. AB - Toxin-mediated vasodilation in the sepsis syndrome can lead to end-organ dysfunction and shock. Assessing for fluid responsiveness and preload optimization with intravenous fluids is a central tenet in the management of sepsis. Aggressive fluid administration can lead to pulmonary edema and heart failure, whereas premature inotropic or vasopressor support can worsen organ perfusion. Inferior vena cava ultrasonography is commonly used to assess for fluid responsiveness but has multiple limitations. PMID- 24238490 TI - Current practice in the management of wound odour: an international survey. AB - AIM: To determine from a multi-disciplinary and international perspective current practice in the management of wound odour. BACKGROUND: Malodour is cited by patients and carers as one of the most distressing and socially isolating aspects of their wounds. The absence of a standardised approach to assessment and management underscores the need to collect baseline data to support guideline development. DESIGN: On-line survey. METHODS: A study specific questionnaire in English, Spanish, Italian and German was emailed to wound care organisations worldwide, palliative and oncology nursing organisations, and known contacts with a special interest in wound management, for distribution to members between December 2011 and February 2012. RESULTS: 1444 people from 36 countries responded. 12% assess odour with descriptive words being the most frequent form of assessment. Charcoal and silver based dressings were the most frequently used odour management agents, yet, only 48.4% and 23% respectively reported these as being very effective. Antimicrobial agents were cited as most effective but were not the most frequently used. 8% use aromatherapy oils direct to the wound, and 74% combine a range of dressings to try and manage odour. Odour, pain and exudate management were the greatest wound management challenges facing patients and clinicians. 46.7% of respondents encounter patients with MFW on a monthly basis and 89% agreed there is a need to develop guidelines in this area. CONCLUSION: A 'trial and error' approach to odour management exists with low overall satisfaction with current practice. There is a need for research and education on means to assess odour and odour management options. PMID- 24238491 TI - The rise and rise of the systematic review. PMID- 24238492 TI - PreImplantation factor (PIF) detection in maternal circulation in early pregnancy correlates with live birth (bovine model). AB - BACKGROUND: Early identification of viable pregnancy is paramount for successful reproduction. Detection of specific signals from pre-implantation viable embryos in normal pregnancy circulation would indicate initiation of embryo-maternal interaction and create a continuum to accurately reflect embryo/fetal well-being post-implantation. Viable mammalian embryos secrete PreImplantation Factor (PIF), a biomarker which plays key, multi-targeted roles to promote implantation, trophoblast invasion and modulate maternal innate and adaptive immunity toward acceptance. Anti-PIF monoclonal antibody (mAb-based chemiluminescent ELISA) accurately detects PIF in singly cultured embryos media and its increased levels correlate with embryo development up to the blastocyst stage. Herein reported that PIF levels (ELISA) in early maternal serum correlate with pregnancy outcome. METHODS: Artificially inseminated (AI) blind-coded Angus cattle (N = 21-23) serum samples (day 10,15 & 20 post-AI) with known calf birth were blindly tested, using both non-pregnant heifers (N = 30) and steer serum as negative controls. Assay properties and anti-PIF monoclonal antibody specificity were determined by examining linearity, spike and recovery experiments and testing the antibody against 234 different circulating proteins by microarray. Endogenous PIF was detected using <3 kDa filter separation followed by anti-PIF mAb-based affinity chromatography and confirmed by ELISA and HPLC. PIF expression was established in placenta using anti-PIF mAb-based IHC. RESULTS: PIF detects viable pregnancy at day 10 post-AI with 91.3% sensitivity, reaching 100% by day 20 and correlating with live calf birth. All non-pregnant samples were PIF negative. PIF level in pregnant samples was a stringent 3 + SD higher as compared to heifers and steer sera. Assay is linear and spike and recovery data demonstrates lack of serum interference. Anti-PIF mAb is specific and does not interact with circulating proteins. Anti-PIF based affinity purification demonstrates that endogenous PIF is what ELISA detects. The early bovine placenta expresses PIF in the trophoblast layer. CONCLUSION: Data herein documents that PIF is a specific, reliable embryo derived biomarker conveniently detectable in early maternal circulation. PIF ELISA emerges as practical tool to detect viable early pregnancy from day 20 post AI. PMID- 24238494 TI - There are some big changes at Health Expectations. PMID- 24238493 TI - The epidemiology of sexually transmitted co-infections in HIV-positive and HIV negative African-Caribbean women in Toronto. AB - BACKGROUND: HIV disproportionately affects African-Caribbean women in Canada but the frequency and distribution of sexually transmitted infections in this community have not been previously studied. METHODS: We recruited women based on HIV status through a Toronto community health centre. Participants completed a socio-behavioural questionnaire using Audio Computer Assisted Self-Interview (ACASI) and provided blood for syphilis, HIV, hepatitis B and C, herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and human cytomegalovirus (CMV) serology, urine for chlamydia and gonorrhea molecular testing and vaginal secretions for bacterial vaginosis (BV) and human papillomavirus (HPV). Differences in prevalence were assessed for statistical significance using chi-square. RESULTS: We recruited 126 HIV-positive and 291 HIV negative women, with a median age of 40 and 31 years, respectively (p < 0.001). Active HBV infection and lifetime exposure to HBV infection were more common in HIV-positive women (4.8% vs. 0.34%, p = 0.004; and 47.6% vs. 21.2%, p < 0.0001), as was a self-reported history of HBV vaccination (66.1% vs. 44.0%, p = 0.0001). Classical STIs were rare in both groups; BV prevalence was low and did not vary by HIV status. HSV-2 infection was markedly more frequent in HIV-positive (86.3%) than HIV-negative (46.6%) women (p < 0.0001). Vaginal HPV infection was also more common in HIV-positive than in HIV-negative women (50.8% vs. 22.6%, p < 0.0001) as was infection with high-risk oncogenic HPV types (48.4% vs. 17.3%, p < 0.0001). CONCLUSIONS: Classical STIs were infrequent in this clinic-based population of African-Caribbean women in Toronto. However, HSV-2 prevalence was higher than that reported in previous studies in the general Canadian population and was strongly associated with HIV infection, as was infection with hepatitis B and HPV. PMID- 24238495 TI - Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model. AB - OBJECTIVE: STAT3 plays a vital role in inducing and maintaining a pro carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases. We investigated the effect of the JAK1/2 inhibitor AZD1480 on lung tumors induced by an activating EGFR mutation. MATERIALS AND METHODS: Three EGFR tyrosine kinase inhibitor-resistant cell lines (RPC-9, PC 9/Van-R and PC-9/ER3) established from PC-9 harboring an EGFR exon19 deletion mutation were used. Growth inhibition was measured using an MTT assay. Effects of AZD1480 were also evaluated in the xenograft model and in the EGFR transgenic mice model. Protein expressions were assessed by immunoblotting and immunohistochemistry. Group differences were compared using Student's t-test. To evaluate the efficacy of AZD1480 on survival, AZD1480 or vehicle was administered orally from 7 weeks of age of the transgenic mice. Overall survival curves were calculated using the Kaplan-Meier method. RESULTS: The sensitivities of resistant and parent cells to AZD1480 were similar in vitro. AZD1480 (30 or 50 mg/kg/day, per os) reduced angiogenesis and revealed significant tumor regression in a mouse xenograft model. Subsequently, the transgenic mice were treated with AZD1480 (30 mg/kg/day) or vehicle alone. The numbers of lung tumors (long axis exceeding 1mm) in the AZD1480-treated group and control group were 0.37+/-0.18 and 2.25+/-0.53 (p<0.001), respectively. AZD1480 treatment suppressed pSTAT3, pJAK1, pJAK2 and angiogenesis. The median survival time in the AZD1480-treated group (217 days) was significantly greater than that in the control group (106 days) (log-rank test, p<0.0001). CONCLUSION: AZD1480 may be effective against lung tumors driven by an activating EGFR mutation. PMID- 24238496 TI - Pleural lavage cytology: where do we stand? AB - Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space. PMID- 24238497 TI - Good news for end stage renal disease patients. PMID- 24238499 TI - Twenty-year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing. AB - BACKGROUND: Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years. METHODS: The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010). RESULTS: Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals. CONCLUSIONS: The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors. PMID- 24238498 TI - Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial. AB - BACKGROUND: A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage. METHODS: Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices. RESULTS: Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L*1.73 m(-2)*w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that. CONCLUSIONS: The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products. PMID- 24238500 TI - Reduction of atrial fibrillation in remotely monitored pacemaker patients: results from a Chinese multicentre registry. AB - BACKGROUND: Many recipients of implantable cardiac electronic devices have atrial fibrillation (AF) occurrences after device implantation, even if there is no previous history of AF, and some of the episodes are asymptomatic. The purpose of this study was to evaluate trends in AF burden following early AF detection in patients treated with pacemakers equipped with automatic, daily Home Monitoring function. METHODS: Between February 2009 and December 2010, the registry recruited 701 pacemaker patients (628 dual-chamber, 73 biventricular devices) at 97 clinical centers in China. Daily Home Monitoring data transmissions were analyzed to screen for the AF burden. In-office follow-ups were scheduled for 3 and 6 months after implantation. Upon first AF (i.e., mode-switch) detection in a patient, screening of AF burden by Home Monitoring was extended for the next 180 days. RESULTS: At least one episode of AF was observed in 22.9% of patients with dual-chamber pacemakers and in 28.8% of patients with biventricular pacemakers. The first AF detection in a patient occurred, on average, about 2 months before scheduled follow-up visits. In both pacemaker groups, mean AF burden decreased significantly (P < 0.05) over 180 days following first AF detection: from 12.0% to 2.5% in dual-chamber and from 12.2% to 0.5% in biventricular pacemaker recipients. The number of patients with an AF burden >10% per month was significantly reduced over 6 months of implantation in both dual chamber (38 patients in the first month vs. 21 patients in month 6, P < 0.05) and biventricular (7 patients in the first month vs. 0 patient in months 4-6, P < 0.05) pacemaker recipients. CONCLUSIONS: Automatic, daily Home Monitoring of patients treated with cardiac pacemakers allows early detection of AF, and there is a gradual and significant decrease in AF burden. PMID- 24238501 TI - Utility of echocardiographic tissue synchronization imaging to redirect left ventricular epicardial lead placement for cardiac resynchronization therapy. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing has demonstrated cardiac function improvement for treating congestive heart failure (HF). It has been documented that the placement of the left ventricular lead at the longest contraction delay segment has the optimal CRT benefit. This study described follow-up to surgical techniques for CRT as a viable alternative for patients with heart failure. METHODS: Between April 2007 and June 2012, a total of 14 consecutive heart failure patients with New York Heart Association (NYHA) Class III-IV underwent left ventricular epicardial lead placements via surgical approach. There were eight males and six females, aged 36 to 79 years ((59.6 +/- 9.2) years). The mean left ventricular ejection fraction (LVEF) was (33.6 +/- 7.4)%. All patients were treated with left ventricular systolic dyssynchrony and underwent left ventricular epicardial lead placements via a surgical approach. Tissue Doppler imaging (TDI) and intraoperative transesophageal echocardiography were used to assess changes in left heart function and dyssynchronic parameters. Also, echo was used to select the best site for left ventricular epicardial lead placement. RESULTS: Left ventricular epicardial leads were successfully implanted in the posterior or lateral epicardial wall without serious complications in all patients. All patients had reduction in NYHA score from III-IV preoperatively to II-III postoperatively. The left ventricular end-diastolic diameter (LVEDD) decreased from (67.9 +/- 12.7) mm to (61.2 +/- 7.1) mm (P < 0.05), and LVEF increased from (33.6 +/- 7.4)% to (42.2 +/- 8.8)% (P < 0.05). Left ventricular intraventricular dyssynchrony index decreased from (148.4 +/- 31.6) ms to (57.3 +/- 23.8) ms (P < 0.05). CONCLUSIONS: Minimally invasive surgical placement of the left ventricular epicardial lead is feasible, safe, and efficient. TDI can guide the epicardial lead placement to the ideal target location. PMID- 24238502 TI - Left atrial minimum volume by real-time three-dimensional echocardiography as an indicator of diastolic dysfunction. AB - BACKGROUND: Left atrial (LA) maximum volume is becoming a prognostic biomarker for left ventricular (LV) diastolic dysfunction. However, we assessed LV diastolic function by measuring LA phasic volumes using real-time threedimensional echocardiography (RT3DE) in patients with stable coronary artery disease (CAD). METHODS: Sixty-five stable CAD patients with normal LV ejection fraction (LVEF) were divided into three groups according to degree of coronary stenosis: control (n = 15) with <50% stenosis as control group, mildS (n = 25) with mild stenosis (50%-70%) and severeS (n = 25) with >70% stenosis. LA phasic volumes and function were evaluated and compared using RT3DE and two dimensional echocardiography (2DE). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were examined. The correlations of RT3DE-derived parameters with other conventional indices were analyzed. RESULTS: Significant correlations between RT3DE and 2DE for LA volume measurements were: control, r = 0.93; mildS, r = 0.94; severeS, r = 0.90 (all P < 0.05). Patients with severe coronary stenosis presented higher NT-proBNP level, indices of LA minimum volume and volume before atrial contraction, but lower LA total emptying fraction (LAEF) and LAEFpassive. Significant correlations of RT3DE derived LA volume indices with E/E' (r = 0.695) and NF-proBNP (r = 0.630) level were found. CONCLUSIONS: RT3DE derived, LA indices correlate well with NT-proBNP level and may be superior to 2DE measurements for the evaluation of LV diastolic dysfunction. Enlargement of LA minimum volume in stable CAD patients without systolic dysfunction appears earlier and may be better correlated with LV diastolic function than that of LA maximum volume. PMID- 24238503 TI - Clinical values of intraoperative indocyanine green fluorescence video angiography with Flow 800 software in cerebrovascular surgery. AB - BACKGROUND: Microscope-integrated near-infrared indocyanine green video angiography (ICG-VA) has been used in neurosurgery for a decade. This study aimed to assess the value of intraoperative indocyanine green (ICG) video angiography with Flow 800 software in cerebrovascular surgery and to discover its hemodynamic features and changes of cerebrovascular diseases during surgery. METHODS: A total of 87 patients who received ICG-VA during various surgical procedures were enrolled in this study. Among them, 45 cases were cerebral aneurysms, 25 were cerebral arteriovenous malformations (AVMs), and 17 were moyamoya disease (MMD). A surgical microscope integrating an infrared fluorescence module was used to confirm the residual aneurysms and blocking of perforating arteries in aneurysms. Feeder arteries, draining veins, and normal cortical vessels were identified by the time delay color mode of Flow 800 software. Hemodynamic parameters were recorded. All data were analyzed by SPSS version 18.0 (SPSS Inc., USA). T-test was used to analyze the hemodynamic features of AVMs and MMDs, the influence on peripheral cortex after resection in AVMs, and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in MMDs. RESULTS: The visual delay map obtained by Flow 800 software had more advantages than the traditional playback mode in identifying the feeder arteries, draining veins, and their relations to normal cortex vessels. The maximum fluorescence intensity (MFI) and the slope of ICG fluorescence curve of feeder arteries and draining veins were higher than normal peripheral vessels (MFI: 584.24+/-85.86 vs. 382.94 +/- 91.50, slope: 144.95 +/- 38.08 vs. 69.20 +/- 13.08, P < 0.05). The arteriovenous transit time in AVM was significantly shorter than in normal cortical vessels ((0.60 +/- 0.27) vs. (2.08 +/- 1.42) seconds, P < 0.05). After resection of AVM, the slope of artery in the cortex increased, which reflected the increased cerebral flow. In patients with MMD, after STA-MCA bypass, cortex perfusion of corresponding branches region increased and local cycle time became shorter. CONCLUSION: Intraoperative ICG video angiography combined with hemodynamic parameter analysis obtained by Flow 800 software appears to be useful for intraoperative monitoring of regional cerebral blood flow in cerebrovascular disease. PMID- 24238504 TI - Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. METHODS: A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. RESULTS: Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. CONCLUSIONS: Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC. PMID- 24238505 TI - Clinical and microbiological features of community-acquired and nosocomial bloodstream infections in the surgical department of a tertiary-care hospital in Beijing. AB - BACKGROUND: Bloodstream infections (BSIs) remain a major cause of morbidity and mortality in patients undergoing surgery. This study aimed at elucidating the clinical characteristics of community-acquired BSIs (CABs) and nosocomial BSIs (nBSIs) in patients admitted to the surgical wards of a teaching hospital in Beijing, China. METHODS: This cross-sectional study compared 191 episodes of BSIs in 4074 patients admitted to the surgical wards between January 2008 and December 2011. Cases of BSIs were classified as CABs or nBSIs, and the characteristics, relevant treatments, and outcomes of CABs and nBSIs were compared. RESULTS: Of the 191 BSIs, 52 (27.2%) and 139 (72.8%) were CABs and nBSIs, respectively. Escherichia coli, coagulasenegative staphylococci, and Klebsiella spp, were the most frequently isolated microorganisms. There were significant differences between CABs and nBSIs with respect to the use of hormonal drugs, ventilation, acute physiology and chronic health evaluation (APACHE) II and American Society of Anesthesiologists scores, and prevalence of cancer (P < 0.05). Empirical antibacterial therapy did not decrease the crude mortality, but multivariate analysis showed that high APACHE II was independently associated with a risk of mortality (odds ratio = 0.97, 95% confidence interval: 0.93-1.02 for APACHE II). CONCLUSIONS: We found significant differences in the clinical characteristics of surgical patients with CABs and nBSIs. The outcome of patients seems to be related to high APACHE II scores. PMID- 24238506 TI - Are there any disbenefits to patients in choosing laparoscopic gastrectomy by an expert in open gastrectomy? Aspects of surgical outcome and radicality of lymphadenectomy. AB - BACKGROUND: There may be concerns over disbenefits to patients who have chosen to undergo laparoscopic gastrectomy by experts in open gastrectomy, considering the disparity between the level of proficiency in open gastrectomy, at which they are already experts, and that in laparoscopic gastrectomy, at which they are beginners. The aim of this study was to compare surgical radicality and outcomes between laparoscopic gastrectomy and open gastrectomy during the learning period of laparoscopic gastrectomy for a senior surgeon who was already an expert in open gastrectomy. METHODS: Data of short-term surgical outcomes were obtained from patients following laparoscopy assisted distal gastrectomy (LADG) by a surgeon. The initial and following 30 experiences were grouped into LADG-I and LADG-II, respectively. Patients who underwent open distal subtotal gastrectomy (ODSG) and yet could have been candidates for LADG were grouped into ODSG. Known indicators of proficiency levels and the postoperative hospital course were compared. The consequences of extended lymphadenectomy, and the radicality of surgery by completing D2 lymphadenectomy were analyzed. RESULTS: The LADG group revealed longer operation time and less bleeding compared to the ODSG group (P < 0.001). The number of retrieved lymph nodes and the rate of complications were not significantly different. In the LADG-I group, the D1+:D2 ratio was 4:1, showing significant differences from those in the LADG-II (0.36:1) and ODSG (0.16:1) groups (P < 0.001). The surgeon was able to complete D2 lymphadenectomy during LADG without significant change in the amount of bleeding and the rate of complications, but with a longer operation time (P = 0.009). The number of lymph nodes from the 12a station was not significantly different between the LADG and ODSG groups with D2 lymphadenectomy. CONCLUSIONS: The surgical outcomes were comparable between LADG and ODSG even during the learning period of LADG, and the equivalence of radicality in lymphadenectomy was soon achieved. As long as the surgeon can accept a long operation time, an expert in open gastrectomy should not refrain from performing laparoscopic gastrectomy in well selected patients because of concerns about disbenefits to patients from choosing laparoscopic gastrectomy over open gastrectomy. PMID- 24238507 TI - Monitoring the source of mesenchymal stem cells in patients after transplantation of mismatched-sex hematopoietic stem cells plus third-party cells. AB - BACKGROUND: In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells (MSCs) remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third party cells. METHODS: In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes: group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry (FCM) was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography (DHPLC) in combination with polymerase chain reaction amplification of short tandem repeats (STRPCR) was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization (FISH) revealed the sex origin of the fifth generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations. RESULTS: The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14+ and CD45+ cells were lower than 0.04% in the fifth generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves. CONCLUSIONS: After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed. PMID- 24238508 TI - Familial tendency in aortic dissection: a value of screening relatives. PMID- 24238509 TI - Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma. AB - BACKGROUND: Tumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma. METHODS: Ninety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People's Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics (FIGO) stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays (SAM) was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by chi(2) test. RESULTS: Analysis between FIGO 1988 stage I and stage III identified a 362-gene "progress signature"; 171 down regulated and 191 up-regulated genes. Among the alterative genes, TARP (T cell receptor gamma alternate reading frame protein) and KRT5 (keratin 5) decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased (P < 0.05). The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased (P < 0.05). In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ (both P < 0.05) both. The expression of P53 had a negative relationship with the expression of KRT5 (P < 0.05), but not with the expression of TARP (P > 0.05). There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN (all P > 0.05). There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 (P > 0.05). CONCLUSION: The expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study. PMID- 24238510 TI - Dynesys dynamic stabilization system for the lumbar degenerative disease: a preliminary report from China. AB - BACKGROUND: Dynesys dynamic stabilization system was first implanted in patients in 1994, and introduced to China in 2007. Therefore, it was a new technique for Chinese orthopedics and hence necessary to collect clinical data about Dynesys in China. The objective of this study was to report the preliminary results of Dynesys for the lumbar degenerative disease in China. METHODS: Twenty-seven patients were treated with the Dynesys between July 2007 and January 2009. The diagnosis included degenerative spondylolisthesis (12 cases), degenerative spinal stenosis (nine cases), and lumbar intervertebral disc herniation (six cases). Back pain and leg pain were evaluated using 100-mm visual analog scales (VAS). The Oswestry Disability Index (ODI) was used to evaluate the patients' function. The intervertebral disc height and range of motion at the operative level were taken on radiographs. RESULTS: All the patients were followed-up, with an average of (22.40 +/- 4.23) months (range 15-32 months). VAS of back pain and leg pain were improved significantly (P < 0.05) at follow-up. The ODI scores were reduced from (62.58 +/- 12.01)% preoperatively to (15.01 +/- 5.71)% at follow-up (P < 0.05). The preoperative mean height of the intervertebral disc was (11.21 +/- 1.58) mm (range 8.5-13.8 mm) and mean was (10.10 +/- 1.78) mm (range 7.0-13.4 mm) at follow-up (P < 0.05). The mean range of motion of the implanted segment was (6.00 +/- 1.79) degrees (range 2.5-9.3 degrees ) preoperatively and (5.47 +/- 1.27) degrees (range 2.9-7.8 degrees ) at follow-up (P = 0.11). CONCLUSIONS: The preliminary results of Dynesys for the lumbar degenerative disease in China are similar to the published results of other countries. It can significantly improve the clinic symptoms and preserved motion at the level of implantation. However, the long-term follow-up data need to be collected. PMID- 24238511 TI - Effects of sorafenib combined with chemoembolization and radiofrequency ablation for large, unresectable hepatocellular carcinomas. AB - BACKGROUND: The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm. METHODS: The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed. RESULTS: During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36 month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis. CONCLUSIONS: Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large scale randomized clinical trials are needed to determine the future role of this treatment. PMID- 24238512 TI - Famitinib in metastatic renal cell carcinoma: a single center study. AB - BACKGROUND: Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC). METHODS: The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent. RESULTS: A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%. CONCLUSIONS: Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable. PMID- 24238513 TI - Total liquid ventilation reduces oleic acid-induced lung injury in piglets. AB - BACKGROUND: Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. The aim of this study is to investigate the effect of total liquid ventilation on oleic acid (OA) induced lung injury in piglets. METHODS: Twelve Chinese immature piglets were induced acute lung injury by OA. Twelve piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes. Samples for blood gas analysis were collected before, and at 60-minute intervals after OA-induced lung injury. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of IL-1beta, IL-6, IL-10 and TNF-alpha in plasma, tissue and bronchoalveolar lavage were analyzed. RESULTS: Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group (P < 0.05). The total lung injury score was also reduced in the study group (P < 0.05). The concentrations of IL-1beta, IL-6, IL-10 and TNF-alpha in plasma, tissue and bronchoalveolar lavage were significantly reduced in the study group (P < 0.05). CONCLUSIONS: Total liquid ventilation reduces biochemical and histologic OA-induced lung injury in piglets. PMID- 24238514 TI - Recurrent double coronary artery-pulmonary fistulae one year after surgical ligation. PMID- 24238515 TI - Effect of refractive correction on ocular optical quality measurement using double-pass system. AB - BACKGROUND: Optical Quality Analysis System II (OQAS, Visiometrics, Terrassa, Spain) that uses double-pass (DP) technique is the only commercially available device that allows objective measurement of ocular retinal image quality. This study aimed to evaluate the impact of spectacle lenses on the ocular optical quality parameters and the validity of the optometer within OQAS. METHODS: Seventy eyes of healthy volunteers were enrolled. Optical quality measurements were performed using OQAS with an artificial pupil diameter of 4.0 mm. Three consecutive measurements were obtained from spectacle correction corresponding to subjective refraction and from the OQAS built-in optometer separately. The modulation transfer function cutoff frequency, the Strehl ratio, the width of the point spread function (PSF) at 10% of its maximal height (PSF10), and the width of the PSF at 50% of its maximal height (PSF50) were analyzed. RESULTS: There was no significant difference in any of the parameters between the spectacle correction and the optometer correction (all P > 0.05, paired t-test). A good agreement was found between both the methods and a good intraobserver repeatability in both the correction methods. Difference in best focus between two methods was the only parameter associated significantly with optical quality parameter differences. Best focus difference, built-in optometer correction with or without external cylindrical lens, and age were associated significantly with PSF10 difference. No linear correlation between refractive status and optical quality measurement difference was observed. A hyperopic bias (best focus difference of (0.50 +/- 0.44) D) and a relatively better optical quality using spectacle correction in high myopia group were found. CONCLUSIONS: OQAS based on DP system is a clinically reliable instrument. In patients with high myopia, measurements using built-in optometer correction should be considered and interpreted with caution. PMID- 24238516 TI - Plasma levels of tissue inhibitor of matrix metalloproteinase-1 correlate with diagnosis and prognosis of glioma patients. AB - BACKGROUND: There is no validated blood biomarker available for glioma management. Invasive growth is the key feature of glioma. We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1), which has less molecular weight than metalloproteinases, as a potential blood biomarker for glioma. METHODS: A total of 285 patients and 59 normal subjects were studied. Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognoses. Longitudinal changes in plasma TIMP-1 during treatment were also evaluated. Plasma matrix metalloproteinase (MMP)-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1. RESULTS: Plasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls (TIMP-1: P < 0.001; MMP-9: P = 0.007). Plasma TIMP-1 increases with increased tumor grade. In Grade IV gliomas, plasma TIMP-1 significantly increased after "successful removal" of the tumor (paired samples t test, before operation vs. during chemotherapy without recurrence, t = -2.131, P = 0.038), but did not change significantly at the time of tumor recurrence (during chemotherapy without recurrence vs. after tumor recurrence, t = -0.652, P = 0.632). High plasma TIMP-1 level correlated with better survival in Grade IV glioma patients (hazard ratio: 0.550, 95% CI: 0.101-1.000, P = 0.036). In Grade IV gliomas, patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1 level (25.23 vs. 18.95 months, log-rank P = 0.045). Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients. CONCLUSIONS: Plasma TIMP 1 is associated with the diagnosis and prognosis of glioma patients. It appears to have better usefulness for guiding clinical decision making than plasma MMP-9. Further studies in an expanded patient population are needed to better define its clinical usefulness. PMID- 24238517 TI - Left ventricular free wall rupture during late mechanical reperfusion for acute myocardial infarction. PMID- 24238518 TI - Effect of epidural analgesia with 0.075% ropivacaine versus 0.1% ropivacaine on the maternal temperature during labor: a randomized controlled study. AB - BACKGROUND: A wealth of evidence has indicated that labor epidural analgesia is associated with an increased risk of hyperthermia and overt clinical fever. Recently, evidence is emerging that the epidural analgesia-induced fever is associated with the types of the epidural analgesia and the variations in the epidural analgesia will affect the incidence of fever. The aim of the present study was to investigate the effects of epidural analgesia with 0.075% or 0.1% ropivacaine on the maternal temperature during labor. METHODS: Two hundred healthy term nulliparas were randomly assigned to receive epidural analgesia with either 0.1% ropivacaine or 0.075% ropivacaine. Epidural analgesia was initiated with 10 ml increment of the randomized solution and 0.5 ug/ml sufentanyl after a negative test dose of 5 ml of 1.5% lidocaine, and maintained with 7 ml bolus doses of the above mentioned mixed analgesics every 30 minutes by the patient controlled epidural analgesia. The measurements included the maternal oral temperature, visual analog scale pain scores, labor events and neonatal outcomes. RESULTS: Epidural analgesia with 0.075% ropivacaine could significantly lower the mean maternal temperature at 4 hours after the initiation of analgesia and the oxytocin administration during labor compared with the one with 0.1% ropivacaine. Moreover, 0.075% ropivacaine treatment could provide satisfactory pain relief during labor and had no significant adverse effects on the labor events and neonatal outcomes. CONCLUSION: Epidural analgesia with 0.075% ropivacaine may be a good choice for the epidural analgesia during labor. PMID- 24238519 TI - Eye-movement study during visual search in Chinese children with developmental dyslexia. AB - BACKGROUND: Developmental dyslexia (DD) is a disorder in which children with normal intelligence and sensory abilities show learning deficits in reading. Abnormal eye movements have been found in DD. However, eye-movement abnormalities during visual search among Chinese children with DD remain unknown. We aimed to identify the eyemovement characteristics and search efficiency of Chinese children with DD during visual search for targets of different conceptual categories, under same-category conditions. METHODS: We compared 32 Chinese dyslexic children and 39 non-dyslexic children in visual search tasks, which were assessed using EyeLink II High-Speed Eye Tracker (SR Research Ltd., Canada). Letters, single Chinese characters, digits, Chinese phrases, figures and facial expressions were used as stimuli. Targets were similar to distractors in meaning, phonology and/or shape. RESULTS: A main effect of task on visual search scores and all eye-movement parameters were found. Search scores, average saccade amplitude and saccade distance were significantly smaller in the DD group than in the controls. An interaction between group and task was found for pupil diameter. CONCLUSIONS: Unlike normal readers, children with DD had a reduction in the visual attention span and search accuracy. Besides, children with DD could not increase their mental workload with increase in task difficulty. The conceptual category of the stimulus materials significantly impacts search speed, accuracy and eye-movement parameters. PMID- 24238520 TI - Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in intrapulmonary lesions. AB - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered to have high value in the staging of mediastinal lymph nodes in lung cancer. The current study was conducted to investigate the diagnostic value of EBUS-TBNA in intrapulmonary lesions located near the central airway. METHODS: From September 2009 to March 2013, 66 patients with pulmonary masses located close to the central airways suspected to be lung cancer were accessed by EBUS-TBNA. Conventional bronchoscopic biopsy before EBUS-TBNA was nondiagnostic in all cases. If EBUS-TBNA did not result in a formal pathological diagnosis of malignancy, patients were subsequently referred for a surgical procedure. RESULTS: Among the 66 cases, 59 were confirmed as pulmonary malignancies by EBUS-TBNA, of which 48 cases were non-small cell lung cancer, nine were small cell lung cancer, and two were metastatic lung tumors. No evidence of malignancy was found by biopsy and histopathological examination in the other seven cases. Thoracoscopy or thoracotomy was subsequently undergone for them. Postoperative pathological examinations confirmed three cases of squamous cell carcinoma of the lung, one case of lymphoma, two cases of sclerosing hemangioma, and one case of pulmonary tuberculoma. The definitive diagnosis rate of EBUS-TBNA for intrapulmonary lesions near the central airway was 89.4%. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing benign from malignant intrapulmonary lesions were 93.7%, 100.0%, and 93.9%, respectively. The positive and negative predictive values were 100.0% and 42.9%, respectively. The EBUS-TBNA procedures were well-tolerated by all patients. No associated complications were observed. CONCLUSIONS: For intrapulmonary lesions near the central airway highly suspected of cancer, EBUS-TBNA has satisfactory diagnostic value. However, the negative predictive value of this technique is low, so negative results obtained by EBUS-TBNA should be confirmed by other methods. PMID- 24238521 TI - Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats. AB - BACKGROUND: Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI), little is known about the AQP4 expression in the early stage of TBI, or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema. The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI. METHODS: One hundred and twenty healthy adult Wistar rats were randomly divided into two groups: sham operation group (SO) and TBI group. The TBI group was divided into five sub-groups according to the different time intervals: 1, 3, 6, 12, and 24 hours. The brains of the animals were taken out at different time points after TBI to measure brain water content. The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM), and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting. The data were analyzed with SPSS 13.0 statistical software. RESULTS: In the SO group, tissue was negative for IgG, and there were no abnormalities in brain water content or AQP4 expression. In the TBI group, brain water content significantly increased at 6 hours and peaked at 24 hours following injury. IgG expression significantly increased from 1 to 6 hours following injury, and remained at a high level at 24 hours. Pathological observation revealed BBB damage at 1 hour following injury. Angioedema appeared at 1 hour, was gradually aggravated, and became obvious at 6 hours. Intracellular edema occurred at 3 hours, with the presence of large glial cell bodies and mitochondrial swelling. These phenomena were aggravated with time and became obvious at 12 hours. In addition, microglial proliferation was visible at 24 hours. AQP4 protein expression were reduced at 1 hour, lowest at 6 hours, and began to increase at 12 hours, showing a V-shaped curve. CONCLUSIONS: The angioedema characterized by BBB damage was the primary type of early traumatic brain edema. It was followed by mixed cerebral edema that consisted of angioedema and cellular edema and was aggravated with time. AQP4 expression was down-regulated during the angioedema attack, but AQP4 expression was upregulated during intracellular edema. PMID- 24238522 TI - Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R. AB - BACKGROUND: Human antigen R (HuR) is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) and HuR participate in the tumor necrosis factor (TNF)-induced expression of interleukin-6 (IL-6). METHODS: Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNA-mediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points. The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. RESULTS: MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. CONCLUSIONS: MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR. PMID- 24238523 TI - Receptor interacting protein 1 involved in ultraviolet B induced NIH3T3 cell apoptosis through expression of matrix metalloproteinases and reactive oxygen species production. AB - BACKGROUND: Receptor interacting protein 1 (RIP1), which plays a key role in apoptosis, cell survival and programmed cell necrosis, is one of the most important proteins in the RIP family. The purpose of this study was to investigate the roles of RIP1 in the apoptosis, the generation of reactive oxygen species (ROS) and the expression of matrix metalloproteinases (MMPs) induced by ultraviolet B (UVB) in fibroblasts. METHODS: siRNA targeting RIP1 was used to silence RIP1 expression in the NIH3T3 fibroblasts. The mRNA and protein levels of MMP-1 and MMP-3, caspase-3 and -8 activities, and ROS activities were determined by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, caspase activity assay, immunofluorescence, and flow cytometry. RESULTS: The mRNA and protein expressions of MMP-1 and MMP-3 were significantly increased in RIP1 deficient NIH3T3 cells at 24 hours after UVB treatment. At 24 hours after exposure to UVB, RIP1 deficient NIH3T3 cells presented apoptotic morphology, and the apoptosis rate was significantly increased accompanied by pronounced increase in caspase-8 and -3 activities. ROS production was inhibited by UVB at 12 hours in RIP1 deficient NIH3T3 cells. CONCLUSION: RIP1 is involved in NIH3T3 cell damage induced by UVB via participating in the apoptosis, expression of MMPs and ROS production. PMID- 24238524 TI - Performance of the microscopic observation drug susceptibility assay in pyrazinamide susceptibility testing for Mycobacterium tuberculosis. AB - BACKGROUND: Drug susceptibility assay is very important in tuberculosis therapy. Pyrazinamide is a first line antituberculosis drug and diagnosis of its resistance in Mycobacterium tuberculosis (M. tuberculosis) is difficult and time consuming by conventional methods. In this study, we aimed to evaluate the performance of the microscopic observation drug susceptibility (MODS) assay in the detection of pyrazinamide resistance in M. tuberculosis relative to the conventional Wayne assay and Lowenstein-Jensen (LJ) proportion method. METHODS: M. tuberculosis clinical isolates (n = 132) were tested by the MODS and the Wayne assay: the results were compared with those obtained by the LJ proportion method. Mutations in the gene were identified by direct sequencing of the pncA genes of all isolates in which pyrazinamide resistance was detected by any of the three methods. RESULTS: Compared to the LJ results, the sensitivity and specificity of the MODS assay were 97.8% and 96.5% respectively; the sensitivity and specificity of the Wayne assay were 87.0% and 97.7% respectively. Mutations in the pncA gene were found in 41 of 46 strains that were pyrazinamide resistant (3 tests), in 1 of the 4 strains (LJ only), in 42 of 48 strains (at least 1 test), but no mutations in 1 strain sensitive according to the MODS assay only. The MODS assay, Wayne assay and LJ proportion method provided results in a median time of 6, 7 and 26 days respectively. CONCLUSIONS: MODS assay offers a rapid, simple and reliable method for the detection of pyrazinamide resistance in M. tuberculosis and is an optimal alternative method in resource limited countries. PMID- 24238525 TI - Surveillance of drug-resistance in Mycoplasma pneumoniae and analysis of clinical features of Mycoplasma pneumoniae pneumonia in childhood. PMID- 24238526 TI - Duct-to-mucosa versus invagination pancreaticojejunostomy after pancreaticoduodenectomy: a meta-analysis. AB - BACKGROUND: Postoperative pancreatic fistula remains one of the most common and troublesome complications following pancreaticoduodenectomy. No consensus exists regarding the optimal pancreaticojejunostomy reconstruction technique to reduce this complication. We aimed to perform a systematic review comparing two commonly used techniques of pancreaticojejunostomy reconstruction (duct-to-mucosa versus invagination), by meta-analysis and assessment of evidence quality. METHODS: Databases searched including The Cochrane Library, Medline, PubMed, Embase, etc. Randomized controlled trials (RCTs) comparing duct-to-mucosa and invagination pancreaticojejunostomy were included. Outcomes of interest were pancreatic fistula rate, mortality, morbidity, reoperation and hospital stay. Pooled estimates were expressed as risk ratio (RR) or mean difference. RESULTS: From 321 identified abstracts, four RCTs (467 patients; duct-to-mucosa: 232; invagination: 235) were included. Pancreatic fistula rate (RR, 0.74; 95% confidence interval (CI): 0.24-2.28; P = 0.60), mortality (RR, 1.18; 95% CI: 0.39- 3.54; P = 0.77), morbidity (RR, 0.91; 95% CI: 0.69-1.21; P = 0.53), reoperation (RR, 1.09; 95% CI: 0.54-2.22; P = 0.81) and hospital stay (mean difference, -1.78; 95% CI: -4.60 1.04; P = 0.22) were similar between techniques. CONCLUSIONS: Duct-to-mucosa and invagination pancreaticojejunostomy are comparable with regards to assessed parameters. High-quality, large-volume, multi-center RCTs with standard outcome definitions are required. PMID- 24238527 TI - Old age security in rural China: there is a long way to go. AB - OBJECTIVE: We aimed to examine the current developments and challenges confronted by old age security in rural China. DATA SOURCES: This study is based on the data from PubMed, Elsevier, Wiley, EBSCO, EMBASE, SCI Expanded, ProQuest, Google, and CNKI which is the most informative database in Chinese. STUDY SELECTION: Articles were selected with the search terms "rural", "China", "old", "older", or "elder", "elderly", or "aged", "aging", "security", "culture", "value", "medical insurance" or "community based medical insurance" or "cooperative medical scheme". Related websites and yearbooks were searched as well. RESULTS: The socio economic development has made the burden of traditional care for the rural elderly heavier than ever, and new challenges are emerging in rural communities, such as poor economic, deteriorating natural environment and health crisis. CONCLUSIONS: The governments should improve the scale and caliber of rural old age security and strengthen regulations with great efforts in developing the rural economy and protecting the natural environment of rural communities. PMID- 24238528 TI - Association between clinical features and prognosis of patients with limb-shaking transient ischemic attack. AB - OBJECTIVE: This review aims to illustrate the relationship between clinical features and the prognosis of patients with limb-shaking transient ischemic attack (LS-TIA). DATA SOURCES: Relevant articles published in two main Chinese medical periodical databases (China National Knowledge Infrastructure and China Science Periodical Database) from 1986 to June 2013 were identified with keywords "limb shaking" and "transient ischemic attack". STUDY SELECTION: Original articles and case reports about LS-TIA were selected. RESULTS: A total of 63 cases collected from 19 articles were included in the pooled analysis. LS-TIA presented in two cerebrovascular diseases, of which atherosclerotic high-grade stenosis or occlusion in carotid artery system and moyamoya disease formed 95.2% and 4.8%, respectively. Of 63 patients, 11 (17.5%) were once misdiagnosed as epileptic and prescribed useless antiepilepsy drugs. The multivariable Logistic regression model showed a significant protective effect of patients with revascularization therapy on prognosis, compared with patients treated with drugs (odds ratio 0.20, 95% CI 0.05-0.74, P = 0.016). CONCLUSIONS: Chronic carotid artery system hypoperfusion can induce limb(s) shaking, followed by high possibility of ischemic stroke in the same brain territorial. Revascularization of the responsible artery may work better than conservative drug-based therapy. PMID- 24238529 TI - Role of mitochondria in the pathogenesis and treatment of glaucoma. AB - OBJECTIVE: To gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma. DATA SOURCES: The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "mitochondria", "glaucoma" and "trabecular meshwork" or "retinal ganglion cells". STUDY SELECTION: Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. RESULTS: Mitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma. CONCLUSIONS: Mitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage. PMID- 24238530 TI - Atrial fibrillation in China. PMID- 24238531 TI - Clinical manifestations of imaging demonstrations of AIDS-related nervous system infections. PMID- 24238532 TI - Inflammatory malignant fibrous histiocytoma of the lung combined with fungal infection. PMID- 24238533 TI - Treatments of disease relapse after allogeneic stem cell transplantation focusing on donor lymphocyte infusion. PMID- 24238534 TI - Effects of shensongyangxin capsule on heart rate turbulence and heart rate variability in chronic heart failure. PMID- 24238535 TI - Two-directional intercoronary communication: visualization of a very rare coronary anomaly and cause of ischemia. PMID- 24238536 TI - Genetic and phenotypic characteristics of six Chinese families with X-linked juvenile retinoschisis. PMID- 24238537 TI - Cilostazol reduces microalbuminuria in type 2 diabetic nephropathy. PMID- 24238538 TI - Still unsettled issue: antiplatelet therapy after stenting in patients taking oral anticoagulants. PMID- 24238539 TI - A case of myocardial abscess induced by Staphylococcus aureus with typical electrocardiogram of acute myocardial infarction. PMID- 24238540 TI - A case with non-typical clinical course of H7N9 avian influenza. PMID- 24238541 TI - A case of sarcoidosis with systemic sclerosis. PMID- 24238542 TI - P300 waveform and dopamine transporter availability: a controlled EEG and SPECT study in medication-naive patients with schizophrenia and a meta-analysis. AB - BACKGROUND: Reduced P300 event-related potential (ERP) amplitude and latency prolongation have been reported in patients with schizophrenia compared to healthy controls. However, the influence of antipsychotics (and dopamine) on ERP measures are poorly understood and medication confounding remains a possibility. METHOD: We explored ERP differences between 36 drug-naive patients with schizophrenia and 138 healthy controls and examined whether P300 performance was related to dopamine transporter (DAT) availability, both without the confounding effects of medication. We also conducted a random effects meta-analysis of the available literature, synthesizing the results of three comparable published articles and our local study. RESULTS: No overall significant difference was found in mean P300 ERP between patients and controls in latency or in amplitude. There was a significant gender effect, with females showing greater P300 amplitude than males. A difference between patients and controls in P300 latency was evident with ageing, with latency increasing faster in patients. No effect of DAT availability on P300 latency or amplitude was detected. The meta-analysis computed the latency pooled standardized effect size (PSES; Cohen's d) of -0.13 and the amplitude PSES (Cohen's d) of 0.48, with patients showing a significant reduction in amplitude. CONCLUSIONS: Our findings suggest the P300 ERP is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity. PMID- 24238543 TI - Realising the potential of stem-cell research in Europe. PMID- 24238544 TI - Delivering action on preterm births. PMID- 24238545 TI - Ending female genital mutilation in the UK. PMID- 24238546 TI - Polio lessons 2013: Israel, the West Bank, and Gaza. PMID- 24238547 TI - Caring for preterm babies is a test of how we respond to our most vulnerable citizens. PMID- 24238548 TI - Doctors in Syria: saving the lifesavers. PMID- 24238550 TI - Global estimates of homicide risk related to intimate partner violence. PMID- 24238551 TI - Global estimates of homicide risk related to intimate partner violence - Authors' reply. PMID- 24238552 TI - Home visits: a strategy to improve newborn survival. PMID- 24238553 TI - Home visits: a strategy to improve newborn survival - Authors' reply. PMID- 24238554 TI - Home visits: a strategy to improve newborn survival. PMID- 24238555 TI - America's cancer care crisis--is Europe any better? PMID- 24238556 TI - Acute compartment syndrome after minor trauma in a patient with undiagnosed mild haemophilia B. PMID- 24238557 TI - The temporal and spatial profiles of cell loss following experimental spinal cord injury: effect of antioxidant therapy on cell death and functional recovery. AB - BACKGROUND: Traumatic spinal cord injury (SCI)-induced overproduction of endogenous deleterious substances triggers secondary cell death to spread damage beyond the initial injury site. Substantial experimental evidence supports reactive species (RS) as important mediators of secondary cell death after SCI. This study established quantitative temporal and spatial profiles of cell loss, characterized apoptosis, and evaluated the effectiveness of a broad spectrum RS scavenger - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and a combination of MnTBAP plus nitro-L-arginine to prevent cell loss and neurological dysfunction following contusion SCI to the rat spinal cord. RESULTS: By counting the number of surviving cells in spinal cord sections removed at 1, 6, 12, 24, 48, 72 h and 1 week post-SCI and at 0 - 4 mm from the epicenter, the temporal and spatial profiles of motoneuron and glia loss were established. Motoneurons continued to disappear over a week and the losses decreased with increasing distance from the epicenter. Significant glia loss peaked at 24 to 48 h post-SCI, but only at sections 0-1.5 mm from the epicenter. Apoptosis of neurons, motoneurons and astrocytes was characterized morphologically by double immuno staining with cell-specific markers and apoptosis indicators and confirmed by transmission electron microscopy. DNA laddering, ELISA quantitation and caspase-3 activation in the spinal cord tissue indicated more intense DNA fragments and greater caspase-3 activation in the epicenter than at 1 and 2 cm away from the epicenter or the sham-operated sections. Intraperitoneal treatment with MnTBAP + nitro-L-arginine significantly reduced motoneuron and cell loss and apoptosis in the gray and white matter compared with the vehicle-treated group. MnTBAP alone significantly reduced the number of apoptotic cells and improved functional recovery as evaluated by three behavioral tests. CONCLUSIONS: Our temporal and spatial profiles of cell loss provide data bases for determining the time and location for pharmacological intervention. Our demonstration that apoptosis follows SCI and that MnTBAP alone or MnTBAP + nitro-L-arginine significantly reduces apoptosis correlates SCI-induced apoptosis with RS overproduction. MnTBAP significantly improved functional recovery, which strongly supports the important role of antioxidant therapy in treating SCI and the candidacy of MnTBAP for such treatment. PMID- 24238558 TI - Residual stress profiles in veneering ceramic on Y-TZP, alumina and ZTA frameworks: measurement by hole-drilling. AB - OBJECTIVES: The residual stress profile developed within the veneering ceramic during the manufacturing process is an important predicting factor in chipping failures, which constitute a well-known problem with yttria-tetragonal-zirconia polycrystal (Y-TZP) based restorations. The objectives of this study are to measure and to compare the residual stress profile in the veneering ceramic layered on three different polycrystalline ceramic framework materials: Y-TZP, alumina polycrystal (AL) and zirconia toughened alumina (ZTA). METHODS: The stress profile was measured with the hole-drilling method in bilayered disk samples of 19 mm diameter with a 0.7 mm thick Y-TZP, AL or ZTA framework and a 1.5mm thick layer of the corresponding veneering ceramic. RESULTS: The AL samples exhibited increasing compressive stresses with depth, while compressive stresses switching into interior tensile stresses were measured in Y-TZP samples. ZTA samples exhibited compressive stress at the ceramic surface, decreasing with depth up to 0.6mm from the surface, and then becoming compressive again near the framework. SIGNIFICANCE: Y-TZP samples exhibited a less favorable stress profile than those of AL and ZTA samples. Results support the hypothesis of the occurrence of structural changes within the Y-TZP surface in contact with the veneering ceramic to explain the presence of tensile stresses. Even if the presence of Y-TZP in the alumina matrix seems to negatively affect the residual stress profiles in ZTA samples in comparison with AL samples, the registered profiles remain positive in terms of veneer fracture resistance. PMID- 24238559 TI - Decitabine alters the expression of Mecp2 isoforms via dynamic DNA methylation at the Mecp2 regulatory elements in neural stem cells. AB - BACKGROUND: Aberrant MeCP2 expression in brain is associated with neurodevelopmental disorders including autism. In the brain of stressed mouse and autistic human patients, reduced MeCP2 expression is correlated with Mecp2/MECP2 promoter hypermethylation. Altered expression of MeCP2 isoforms (MeCP2E1 and MeCP2E2) is associated with neurological disorders, highlighting the importance of proper regulation of both isoforms. While known regulatory elements (REs) within the MECP2/Mecp2 promoter and intron 1 are involved in MECP2/Mecp2 regulation, Mecp2 isoform-specific regulatory mechanisms are unknown. We hypothesized that DNA methylation at these REs may impact the expression of Mecp2 isoforms. METHODS: We used a previously characterized in vitro differentiating neural stem cell (NSC) system to investigate the interplay between Mecp2 isoform specific expression and DNA methylation at the Mecp2 REs. We studied altered expression of Mecp2 isoforms, affected by global DNA demethylation and remethylation, induced by exposure and withdrawal of decitabine (5-Aza-2' deoxycytidine). Further, we performed correlation analysis between DNA methylation at the Mecp2 REs and the expression of Mecp2 isoforms after decitabine exposure and withdrawal. RESULTS: At different stages of NSC differentiation, Mecp2 isoforms showed reciprocal expression patterns associated with minor, but significant changes in DNA methylation at the Mecp2 REs. Decitabine treatment induced Mecp2e1/MeCP2E1 (but not Mecp2e2) expression at day (D) 2, associated with DNA demethylation at the Mecp2 REs. In contrast, decitabine withdrawal downregulated both Mecp2 isoforms to different extents at D8, without affecting DNA methylation at the Mecp2 REs. NSC cell fate commitment was minimally affected by decitabine under tested conditions. Expression of both isoforms negatively correlated with methylation at specific regions of the Mecp2 promoter, both at D2 and D8. The correlation between intron 1 methylation and Mecp2e1 (but not Mecp2e2) varied depending on the stage of NSC differentiation (D2: negative; D8: positive). CONCLUSIONS: Our results show the correlation between the expression of Mecp2 isoforms and DNA methylation in differentiating NSC, providing insights on the potential role of DNA methylation at the Mecp2 REs in Mecp2 isoform-specific expression. The ability of decitabine to induce Mecp2e1/MeCP2E1, but not Mecp2e2 suggests differential sensitivity of Mecp2 isoforms to decitabine and is important for future drug therapies for autism. PMID- 24238560 TI - Understanding significant processes during work environment interventions to alleviate time pressure and associated sick leave of home care workers--a case study. AB - BACKGROUND: Ergonomic and work stress interventions rarely show long-term positive effect. The municipality participating in this study received orders from the Norwegian Labour Inspectorate due to an identified unhealthy level of time pressure, and responded by effectuating several work environment interventions. The study aim is to identify critical factors in the interaction between work environment interventions and independent rationalization measures in order to understand a potential negative interfering effect from concurrent rationalizations on a comprehensive work environment intervention. METHODS: The study, using a historic prospective mixed-method design, comprised 6 home care units in a municipality in Norway (138 respondents, response rate 76.2%; 17 informants). The study included quantitative estimations, register data of sick leave, a time line of significant events and changes, and qualitative descriptions of employee appraisals of their work situation gathered through semi structured interviews and open survey responses. RESULTS: The work environment interventions were in general regarded as positive by the home care workers. However, all units were simultaneously subjected to substantial contextual instability, involving new work programs, new technology, restructurings, unit mergers, and management replacements, perceived by the home care workers to be major sources of stress. Findings suggest that concurrent changes induced through rationalization resulted in negative exposure effects that negated positive work environment intervention effects, causing an overall deteriorated work situation for the home care workers. CONCLUSIONS: Establishment and active utilization of communication channels from workers to managers are recommended in order to increase awareness of putative harmful and interruptive effects of rationalization measures. PMID- 24238562 TI - Decomposition of nitrotoluenes in wastewater by sonoelectrochemical and sonoelectro-Fenton oxidation. AB - Oxidative degradation of dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) in wastewater was conducted using electrochemical and electro-Fenton processes respectively, combined with ultrasonic irradiation, wherein a synergistic effect is observed. Experiments were carried out to elucidate the influence of various operating variables on the sonoelectrolytic behavior, such as electrode potential, sonoelectrolytic temperature, acidity of wastewater, oxygen dosage, and dosage of ferrous ions. It deserves to note that the nitrotoluene contaminants could be completely decomposed by sonoelectro-Fenton method, wherein hydrogen peroxide was in situ generated from cathodic reduction of oxygen, supplied partially by anodic oxidation of water. During the sonoelectrolytic process, in spite of existence of degassing phenomenon, the high yield of hydrogen peroxide was produced due to the significantly enhanced mass transfer rate of oxygen toward the cathode, caused by ultrasonic irradiation. Because higher removal efficiency of DNTs and TNT obtained at ambient conditions, it is believed that the sonoelectrolytic method is potentially applied to dispose wastewater from toluene nitration processes. PMID- 24238561 TI - Prevalence of depression and associated risk factors among persons with type-2 diabetes mellitus without a prior psychiatric history: a cross-sectional study in clinical settings in urban Nepal. AB - BACKGROUND: Diabetes is a growing health problem in South Asia. Despite an increasing number of studies exploring causal pathways between diabetes and depression in high-income countries (HIC), the pathway between the two disorders has received limited attention in low and middle-income countries (LMIC). The aim of this study is to investigate the potential pathway of diabetes contributing to depression, to assess the prevalence of depression, and to evaluate the association of depression severity with diabetes severity. This study uses a clinical sample of persons living with diabetes sequelae without a prior psychiatric history in urban Nepal. METHODS: A cross-sectional study was conducted among 385 persons living with type-2 diabetes attending tertiary centers in Kathmandu, Nepal. Patients with at least three months of diagnosed diabetes and no prior depression diagnosis or family history of depression were recruited randomly using serial selection from outpatient medicine and endocrine departments. Blood pressure, anthropometrics (height, weight, waist and hip circumference) and glycated hemoglobin (HbA1c) were measured at the time of interview. Depression was measured using the validated Nepali version of the Beck Depression Inventory (BDI-Ia). RESULTS: The proportion of respondents with depression was 40.3%. Using multivariable analyses, a 1-unit (%) increase in HbA1c was associated with a 2-point increase in BDI score. Erectile dysfunction was associated with a 5-point increase in BDI-Ia. A 10 mmHg increase in blood pressure (both systolic and diastolic) was associated with a 1.4-point increase in BDI-Ia. Other associated variables included waist-hip-ratio (9-point BDI-Ia increase), at least one diabetic complication (1-point BDI-Ia increase), treatment non-adherence (1-point BDI-Ia increase), insulin use (2-point BDI-Ia increase), living in a nuclear family (2-point BDI-Ia increase), and lack of family history of diabetes (1-point BDI-Ia increase). Higher monthly income was associated with increased depression severity (3-point BDI-Ia increase per 100,000 rupees, equivalent US$1000). CONCLUSIONS: Depression is associated with indicators of more severe diabetes disease status in Nepal. The association of depression with diabetes severity and sequelae provide initial support for a causal pathway from diabetes to depression. Integration of mental health services in primary care will be important to combat development of depression among persons living with diabetes. PMID- 24238563 TI - Treatment and 5-year survival in patients with nonmetastatic prostate cancer: the Norwegian experience. AB - OBJECTIVE: To establish the 5-year overall and prostate cancer-specific survival in 3486 patients with a new diagnosis of nonmetastatic prostate cancer recorded in the Norwegian Prostate Cancer Registry in 2004-2005. METHODS: The eligible patients were <=75 years old and had undergone radical prostatectomy (n = 895), high-dose radiotherapy with or without adjuvant hormonal therapy (n = 1339), or no local treatment (n = 1252). Kaplan-Meier estimates, Cox regression analyses, and competing risk methods were used. RESULTS: For all patients, the overall and prostate cancer-specific survival was 89.8% (95% confidence interval 88.8-90.8) and 96.5% (95% confidence interval 95.9-97.1), respectively. Less than 1% of the 76 deaths in patients with low-risk tumors were from prostate cancer. Among the patients with high-risk tumors in the no local treatment group, 48% of the 207 deaths were from prostate cancer compared with 33% of the 81 deaths in the radical prostatectomy and radiotherapy groups (P = .03). On multivariate analysis, local treatment (yes vs no), tumor risk category, and performance status were independently associated with prostate cancer survival, but age was not. No significant differences emerged between the radical prostatectomy and radiotherapy groups. A lack of local treatment and a reduced performance status were significantly associated with reduced prostate cancer-specific survival. CONCLUSION: Although based on only 5 years of observation, we have concluded that patients with low-risk tumors should be informed about the option of active surveillance. Patients with high-risk tumors run a risk of undertreatment if local treatment is not applied. The correct identification of tumor risk categories and comorbidity at the diagnosis of nonmetastatic prostate cancer remains a challenge for clinicians. PMID- 24238564 TI - Anatomy of the dorsal nerve of the penis, clinical implications. AB - OBJECTIVE: To show the branching patterns and the anatomic variations of the dorsal nerve of the penis (DNP) along the penile shaft, particularly the relation with the tunica albuginea. METHODS: The penises of 22 adult cadavers were dissected. The number and the diameters of the branches, the presence of anastomoses between the main trunks, the positioning of the nerves before entering the glans penis, and the presence of branches emerging from the body of the DNP and perforating the tunica albuginea were noted and photographed. The compartments where the anatomic findings were located were noted. RESULTS: The DNP was composed of 2, 3, 4, 5, and 6 main branches in 6 (27.3%), 6 (27.3%), 6 (27.3%), 1 (4.5%), and 3 (13.6%) of 22 dissections, respectively. We could trace 2, 3, 4, and 5 terminal branches of the DNP going into the glans penis in 4 (18.2%), 8 (36.4%), 7 (31.8%), and 3 (13.6%) dissections, respectively. In 2 dissections (9.1%), fine branches were present between the main trunks crossing the midline. Anastomosing branches between ipsilateral main trunks of the DNP were identified in 5 dissections (22.7%). In 16 (72.7%) dissections, branches emerging from the inferior aspect of the body of the DNP, which perforated the tunica albuginea, could be identified. CONCLUSION: The exact anatomic knowledge of the DNP is mandatory during penile reconstructive surgeries. The presence of branches perforating the tunica albuginea is the most important finding of this cadaveric study, together with the other documented variations, which must be taken into consideration during penile reconstructive surgeries. PMID- 24238566 TI - Editorial comment. PMID- 24238569 TI - Epidermal growth factor receptor-targeted therapy in squamous cell carcinoma of the penis: a report of 3 cases. AB - OBJECTIVE: To describe 3 cases of advanced refractory penile cancer treated with targeted therapy against the epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: We identified 3 patients with advanced penile cancer who had disease progression after platinum chemotherapy refractory and who subsequently received EGFR-targeted therapy. Their tumor tissue was evaluated for expression of EGFR by immunohistochemistry and messenger ribonucleic acid quantitation and was also tested for the presence of human papillomavirus deoxyribonucleic acid by line hybridization. K-ras mutation was evaluated by polymerase chain reaction for 6 mutations in codon 12 and 1 mutation in codon 13. RESULTS: One patient responded to cetuximab and remains disease-free 42 months after presentation. One patient responded to panitumumab, then suffered relapse. One other progressed through EGFR-targeted therapy. EGFR expression by immunohistochemistry was 1-2+ in all cases, and messenger ribonucleic acid expression ranged from 4.08 to 7.33. No K ras mutations or human papillomavirus deoxyribonucleic acid was detected. CONCLUSION: We report 3 cases in which EGFR-targeted therapy was used to treat platinum-refractory penile cancer patients. Because 2 of the 3 had clinical benefit, future prospective trials of EGFR-targeted therapy in penile cancer are warranted. PMID- 24238570 TI - Editorial comment. PMID- 24238571 TI - Editorial comment. PMID- 24238572 TI - The fate of the remaining knee(s) or hip(s) in osteoarthritic patients undergoing a primary TKA or THA. AB - The purpose of this study was to determine the fate of the remaining hip(s) and knee(s) following an initial total hip or knee arthroplasty in 5352 patients with idiopathic osteoarthritis who were followed for a minimum ten years (mean 17.8 +/ 5.7 years). Following an initial primary TKA, 46.0% of patients had a contralateral TKA, 2.3% had an ipsilateral THA and 1.3% had a contralateral THA. Following an initial primary THA, 30.5% of patients had a contralateral THA, 6.8% had an ipsilateral TKA and 2.9% had a contralateral TKA. Cox regression analysis demonstrated that BMI was the sole risk factor for a second THA, but both age less than sixty years and a higher BMI were significant factors for patients requiring an additional primary TKA. PMID- 24238573 TI - Serum procalcitonin in Egyptian patients with acute meningitis and a negative direct cerebrospinal fluid examination. AB - BACKGROUND: To reduce the morbidity and mortality related to bacterial meningitis, it is important to discriminate bacterial meningitis from aseptic meningitis during the acute phase of the disease, when the clinical symptoms are often similar. OBJECTIVES: To test the reliability of serum procalcitonin (PCT) to discriminate bacterial meningitis from aseptic meningitis in patients who have a negative direct cerebrospinal fluid (CSF) examination, and to evaluate the role of serum PCT to assess treatment efficacy compared with the total leukocyte count (TLC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). MATERIALS AND METHODS: Forty patients with suspected acute meningitis and negative gram stains were included, and ten healthy persons were included as controls. According to the clinical examination and the CSF cytochemical analysis and cultures, the patients were divided into bacterial and aseptic groups. The measurements of serum PCT, ESR, CRP and TLC were performed. RESULTS: Patients in the bacterial group had a higher value of serum PCT at admission and at 3 days post-treatment than those in the aseptic group, with a highly significant difference between them. CONCLUSION: Serum PCT and, to a lesser extent, TLC had prognostic value in patients with acute meningitis, and PCT is more useful because it can be frequently measured for the diagnosis and follow-up of bacterial meningitis. PMID- 24238575 TI - Quality assurance for care of melanoma patients based on guideline-derived quality indicators and certification. AB - BACKGROUND AND OBJECTIVES: In 2013 the first German S-3 guidelines on the diagnosis, treatment, and follow-up of melanoma were published in the framework of the German Guideline Program on Oncology. Quality indicators were developed at the same time as the guideline development process in order to implement the guideline recommendations. PATIENTS AND METHODS: A multidisciplinary, interprofessional working group developed quality indicators following a standardized process. RESULTS: Twelve quality indicators directly linked to guideline recommendations were generated and agreed on by consensus. They were integrated into the catalogue of requirements for dermato-oncological centers certified by the German Cancer Society. CONCLUSIONS: The close cooperation between the guideline group and commission for certification allowed the guideline contents to be implemented in the form of quality indicators in everyday clinical practice. Adherence to the guidelines is required and continuously evaluated as part of certification. PMID- 24238574 TI - The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation. AB - INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13 related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC. PMID- 24238576 TI - How young is too young: ethical concerns in genital surgery of the transgender MTF adolescent. AB - INTRODUCTION: During the last decade, the age of youths presenting for gender confirmation has steadily fallen. Transgender adolescents are being treated with gonadotropin-releasing hormone analogues and subsequently cross-sex hormones at early or midpuberty, with genital surgery as the presumed final step in treatment for female-affirmed (male-to-female) individuals. Despite the minimum age of 18 as eligibility to undergo irreversible procedures, anecdotal reports show that vaginoplasties of female-affirmed patients under 18 have been performed by surgeons, thereby contravening the World Professional Association for Transgender Health Standards of Care. AIM: The purpose of this article is (i) to provide a review of salient factors regarding genital surgery in transgender adolescents; (ii) to review various ethical protocols for determining maturity in gender dysphoric individuals under 18; and (iii) to present a new systematic set of ethical principles largely derived from the surgical management of youths with disorders of sex development and adapted to the needs of transitioning adolescents. METHODS: A literature review of the topic was performed. Ethical guidelines derived from applied treatment protocols of children with disorders of sex development were written. MAIN OUTCOME MEASURE: Progressing from the current state of ethical standards and clinical assumptions, a new development of ethical guidelines for genital surgery in the female-affirmed transgender adolescent was created. RESULTS: There were no controlled studies of vaginoplasties performed on female-affirmed adolescents under 18 years of age. A new set of ethical guidelines was created in order to support treatment professionals in their decision making process. CONCLUSIONS: Professionals across disciplines treating female-affirmed adolescents can utilize the proposed ethical guidelines to facilitate decision making on a case-by-case basis in order to protect both patients and practitioners. These guidelines may also be used in support of more open discussions and disclosures of surgical results that could further the advancement of treatment in this emerging population. PMID- 24238577 TI - Mortality from nonneoplastic skin disease in the United States. AB - BACKGROUND: The mortality burden from nonneoplastic skin disease in the United States is unknown. OBJECTIVE: We sought to estimate mortality from nonneoplastic skin disease as underlying and contributing causes of death. METHODS: Population based death certificate data detailing mortality from nonneoplastic skin disease for years 1999 to 2009 were used to calculate absolute numbers of death and age adjusted mortality by year, patient demographics, and 10 most commonly reported diagnoses. RESULTS: Nonneoplastic skin diseases were reported as underlying and contributing causes of mortality for approximately 3948 and 19,542 patients per year, respectively. Age-adjusted underlying cause mortality (per 100,000 persons) were significantly greater (P < .0001) for patients who were black/African American (3.4), women (1.4), and residing in the South (1.6). Most deaths occurred in patients ages 65 years and older (34,248 total deaths). Common underlying causes of death included chronic ulcers (1789 deaths/y) and cellulitis (1348 deaths/y). LIMITATIONS: Errors in death certificate data and inability to adjust for patient-level confounders may limit the accuracy and generalizability of our results. CONCLUSION: Mortality from nonneoplastic skin disease is uncommon yet potentially preventable. The elderly bear the greatest burden of mortality from nonneoplastic skin disease. Chronic ulcers and cellulitis constitute frequent causes of death. PMID- 24238579 TI - Current Problems in Cancer. Bone tumors in children and young adults. Foreword. PMID- 24238578 TI - Prevalence of chronic kidney disease across levels of glycemia among adults in Pudong New Area, Shanghai, China. AB - BACKGROUND: Few population-based studies have examined the relationship between glycemic status and chronic kidney disease (CKD) in China. We examined the prevalence of CKD across categories of glycemia [diagnosed diabetes, undiagnosed diabetes (fasting plasma glucose [FPG] >= 126 mg/dL), prediabetes (FPG 100-126 mg/dL) and normal glycemia (FPG <100 mg/dL)] among Chinese adults and assessed the relative contribution of dysglycemia (prediabetes and/or diabetes) to the burden of CKD. METHODS: 5,584 Chinese adults aged 20-79 years were selected from the Pudong New Area of Shanghai through a multistage random sampling. Demographic and lifestyle characteristics, anthropometry and blood pressure were measured. Biochemical assays included FPG, serum creatinine and lipids, urinary creatinine and albumin. Prevalence of albuminuria [urine albumin-to-creatinine ratio (ACR) >= 30 mg/g], decreased kidney function and CKD (either decreased kidney function or albuminuria) across levels of glycemia were estimated. RESULTS: The prevalence of albuminuria, decreased kidney function and CKD each increased with higher glycemic levels (P < 0.001). Based on the MDRD Study equation, the unadjusted CKD prevalence was 30.9%, 28.5%, 14.1% and 9.2% in those with diagnosed diabetes, undiagnosed diabetes, prediabetes and normoglycemia, respectively. The corresponding age-, gender- and hypertension-adjusted CKD prevalence were 25.8%, 25.0%, 12.3% and 9.1%, respectively. In a multivariable analysis, the factors associated with CKD were hypertension (Odds ratio [OR] 1.70, 95% confidence interval [CI]: 1.42-2.03), dysglycemia (OR 1.65, 95% CI: 1.39-1.95), female gender (OR 1.48, 95% CI: 1.25-1.75), higher triglycerides (OR 1.14, 95% CI: 1.08 1.20 per mmol/L), higher body mass index (OR 1.08, 95% CI: 1.05-1.10 per kg/m2), and older age (OR 1.02, 95% CI: 1.01 -1.03 per year). The population attributable risks (PARs) associated with diabetes, prediabetes, dysglycemia (diabetes and prediabetes) and hypertension were 18.4%, 19.7%, 30.3% and 44.5% for CKD as defined by the MDRD study equation, and 15.8%, 24.4%, 29.2% and 10.0% with the CKD-EPI equation. Estimates of prevalence and ORs of the relative contribution of various risk factors to CKD obtained with the CKD-EPI equation were similar. CONCLUSIONS: As much as 30% of the CKD burden may be associated with dysglycemia among Chinese adults, independent of age, gender and hypertension status. Prevention and control of diabetes and prediabetes should be a high priority in reducing the CKD burden in China. PMID- 24238580 TI - Introduction: Malignant primary bone tumors in children and young adults. PMID- 24238581 TI - Clinical presentation of bone tumors in children and young adults. PMID- 24238582 TI - The pathophysiology of primary bone tumors in young adults and children. PMID- 24238583 TI - The role of imaging of malignant bone tumors in children and young adults. PMID- 24238584 TI - Surgery in malignant bone tumors. PMID- 24238585 TI - Radiation therapy in primary bone tumors for young patients. PMID- 24238586 TI - Standard chemotherapy for malignant bony tumors in children and young adults. PMID- 24238587 TI - Metastatic and recurrent bone primary bone cancers. PMID- 24238588 TI - Future directions for pediatric and young adult bone sarcoma. PMID- 24238589 TI - Survivorship in young patients with bone cancer. PMID- 24238590 TI - Evaluation of a cornstarch-based ultrasound gel alternative for low-resource settings. AB - BACKGROUND: Ultrasound is an ideal imaging modality for low-resource settings given its portability, ease of use, and wide range of applications. Commercially available ultrasound gels may be unavailable or cost prohibitive in low-resource settings. OBJECTIVE: Our aim was to investigate the quality of images obtained with an alternative ultrasound gel made from cornstarch and water in comparison with commercially available gel. METHODS: The cornstarch gel was made by heating water and cornstarch. The gel was used to obtain standard ultrasound images of the gallbladder, kidneys, bladder, heart, and neck vessels by the study investigators. Commercial gel was used as the control. Twenty-four ultrasound clips were shown to four blinded radiologists and two ultrasound-fellowship trained emergency department physicians. They rated the images on adequacy (yes/no) and graded the images detail, resolution, and quality using a continuous 0-10 scale. RESULTS: A total of 144 video clips were shown to reviewers and 129 data-collection sheets were returned. There was no statistical difference in the proportion of images deemed to be of adequate quality: cornstarch-based gel = 0.97 (95% confidence interval [CI] 0.92-1.00) vs. commercially available gel = 0.85 (95% CI 0.75-0.94) (p = 0.053). The cornstarch gel was superior to commercial gel on all three image parameters: detail (p = 0.002), resolution (p = 0.018), and quality (p = 0.013). CONCLUSIONS: In this study, a gel made from cornstarch and water was an acceptable coupling medium and provided equally adequate images as compared with commercial ultrasound gel. This inexpensive gel made from ubiquitous materials can be an acceptable alternative to commercial gel in low-resource settings. PMID- 24238591 TI - Intercavernous carotid artery aneurysm. PMID- 24238593 TI - Cosmetic mydriasis. PMID- 24238592 TI - "Push as hard as you can" instruction for telephone cardiopulmonary resuscitation: a randomized simulation study. AB - BACKGROUND: The medical priority dispatch system (MPDS(r)) assists lay rescuers in protocol-driven telephone-assisted cardiopulmonary resuscitation (CPR). OBJECTIVE: Our aim was to clarify which CPR instruction leads to sufficient compression depth. METHODS: This was an investigator-blinded, randomized, parallel group, simulation study to investigate 10 min of chest compressions after the instruction "push down firmly 5 cm" vs. "push as hard as you can." Primary outcome was defined as compression depth. Secondary outcomes were participants exertion measured by Borg scale, provider's systolic and diastolic blood pressure, and quality values measured by the skill-reporting program of the Resusci((r)) Anne Simulator manikin. For the analysis of the primary outcome, we used a linear random intercept model to allow for the repeated measurements with the intervention as a covariate. RESULTS: Thirteen participants were allocated to control and intervention. One participant (intervention) dropped out after min 7 because of exhaustion. Primary outcome showed a mean compression depth of 44.1 mm, with an inter-individual standard deviation (SDb) of 13.0 mm and an intra individual standard deviation (SDw) of 6.7 mm for the control group vs. 46.1 mm and a SDb of 9.0 mm and SDw of 10.3 mm for the intervention group (difference: 1.9; 95% confidence interval -6.9 to 10.8; p = 0.66). Secondary outcomes showed no difference for exhaustion and CPR-quality values. CONCLUSIONS: There is no difference in compression depth, quality of CPR, or physical strain on lay rescuers using the initial instruction "push as hard as you can" vs. the standard MPDS((r)) instruction "push down firmly 5 cm." PMID- 24238594 TI - Ring removal. PMID- 24238595 TI - We have compelling indications for antihypertensives, but not for parenteral anticoagulants. PMID- 24238596 TI - Adrenal insufficiency as the presenting feature in a patient with lung cancer. PMID- 24238597 TI - Bilateral luxatio erecta: a case report. AB - BACKGROUND: Luxatio erecta humeri or inferior dislocation of the glenohumeral joint is a rare presentation in the emergency department that is typically caused by a direct loading force on a fully abducted arm. This type of shoulder dislocation represents only 0.5% of all shoulder dislocations, making bilateral cases even more unique. OBJECTIVE: The authors report a case of bilateral luxatio erecta to highlight some of the key clinical signs and discuss proper methods of care. CASE REPORT: We report a case of bilateral luxatio erecta after a forward fall on a treadmill in a senior male patient. The patient grabbed onto the side rails of the treadmill such that his abducted arms received the entire force of the fall. These injuries were successfully reduced in the emergency department of our institution using a two-step approach for each: 1) conversion to anterior dislocation and 2) full reduction. CONCLUSIONS: Although shoulder dislocations remain a commonly seen injury in the emergency department, it is important to consider that not all dislocations are simply anterior. Signature signs of luxatio erecta are fixed abduction at the shoulder with elbow flexion and forearm pronation. The humeral head should be palpable inferior to the glenoid fossa. The most effective treatments for this injury involve sufficient muscle relaxation for reduction, a methodical approach to reduction, and appropriate immobilization. PMID- 24238598 TI - Revisiting the algorithm: are we causing more confusion? PMID- 24238599 TI - Physiologic effects of a new-generation conducted electrical weapon on human volunteers. AB - BACKGROUND: Conducted electrical weapons (CEWs) are used by law enforcement to restrain or repel potentially violent persons. The TASER X2 CEW is a next generation device with new technology, including new electrical waveform and output specifications. It has not previously been studied in humans. OBJECTIVE: The objective of this study was to evaluate the human physiologic effect of a new generation CEW. METHODS: This was a prospective, observational human study. Volunteers received a 10-s exposure via deployed probes from an X2 CEW in the abdomen and upper thigh. Measured data included vital signs; 12-lead electrocardiograms; and blood serum biomarkers before, immediately after, and 24 h post exposure. Biomarkers measured included pH, lactate, potassium, creatine kinase (CK), and troponin-I. Real-time spirometry and echocardiography were performed before, during, and after the exposure. RESULTS: Ten volunteers completed the study. There were no important changes in vital signs or potassium. Median increase in lactate as a consequence of the exposure was 1.2 mg/dL (range 0.6-2.8 mg/dL). Median change in pH was -0.031 (range -0.011 to -0.067). No subject had a positive troponin. Median change in CK at 24 h was 313 ng/mL (range -40 to 3418 ng/mL). There was no evidence of respiratory impairment. Baseline median minute ventilation was 14.2 L/min, increased to 21.6 L/min intra-exposure (p = 0.05), and remained elevated at 21.6 L/min post exposure (p = 0.01). CONCLUSIONS: There was no evidence of dangerous physiology found in the measured parameters. The physiologic effects of the X2 CEW are similar to older-generation CEWs. We encourage further study to validate these results. PMID- 24238600 TI - Imaging endosomes and autophagosomes in whole mammalian cells using correlative cryo-fluorescence and cryo-soft X-ray microscopy (cryo-CLXM). AB - Cryo-soft X-ray tomography (cryo-SXT) is a powerful imaging technique that can extract ultrastructural information from whole, unstained mammalian cells as close to the living state as possible. Subcellular organelles including the nucleus, the Golgi apparatus and mitochondria have been identified by morphology alone, due to the similarity in contrast to transmission electron micrographs. In this study, we used cryo-SXT to image endosomes and autophagosomes, organelles that are particularly susceptible to chemical fixation artefacts during sample preparation for electron microscopy. We used two approaches to identify these compartments. For early and recycling endosomes, which are accessible to externally-loaded markers, we used an anti-transferrin receptor antibody conjugated to 10nm gold particles. For autophagosomes, which are not accessible to externally-applied markers, we developed a correlative cryo-fluorescence and cryo-SXT workflow (cryo-CLXM) to localise GFP-LC3 and RFP-Atg9. We used a stand alone cryo-fluorescence stage in the home laboratory to localise the cloned fluorophores, followed by cryo-soft X-ray tomography at the synchrotron to analyse cellular ultrastructure. We mapped the 3D ultrastructure of the endocytic and autophagic structures, and discovered clusters of omegasomes arising from 'hotspots' on the ER. Thus, immunogold markers and cryo-CLXM can be used to analyse cellular processes that are inaccessible using other imaging modalities. PMID- 24238602 TI - Is the skillset obtained in surgical simulation transferable to the operating theatre? AB - BACKGROUND: Simulated surgical training offers a safe and accessible way of learning surgical procedures outside the operating room. Training programs have been developed using simulated laboratories to train surgical trainees to proficiency outside the operating room. Despite the global enthusiasm among educators to enhance training through simulation-based learning, it remains to be elucidated whether the skill set obtained is transferrable to the operating room. METHODS: Using standardized search methods, the authors searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web-Based Knowledge, as well as the reference lists of relevant articles, and retrieved all published randomized controlled trials. RESULTS: Sixteen randomized controlled trials involving 309 participants were identified to be suitable for qualitative analysis using the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The mean Consolidated Standards of Reporting Trials score was 16 (range, 12-22). The studies showed considerable clinical and methodologic diversity. Operative time improved consistently in all trials after training and was the only objective parameter measurable in the live setting. Studies that used the Objective Structured Assessment of Technical Skills as their primary outcome showed improved scores in 80% of trials, and studies that used performance indicators to assess participants all showed improved scores after simulation training in all of the trials, with 88% showing statistical significance. CONCLUSIONS: The current literature consistently demonstrates the positive impact of simulation on operative time and predefined performance scores. However, these reproducible measures alone are insufficient to demonstrate transferability of skills from the laboratory to the operating room. The authors advocate a multimodal assessment, including metrics, the Objective Structured Assessment of Technical Skills, and critical step completion. This may provide a more complete assessment of operative performance. Only then can it be concluded that simulation skills are transferable to the live operative setting. PMID- 24238603 TI - Cutting too deep? Assessing the impact of a shorter surgery clerkship on students' clinical skills and knowledge. AB - BACKGROUND: The aim of this study was to compare the performance of students completing an 8-week versus a 6-week surgery clerkship on an objective structured clinical examination (OSCE) and the National Board of Medical Examiners (NBME) clinical science surgery examination. METHODS: One hundred fifteen students from the 8-week clerkship and 99 from the 6-week clerkship were included. Performance on a summative OSCE was assessed using behaviorally anchored checklists. NBME exams were graded using the NBME's standard scaled scores. Results were compared using 2-tailed, independent-samples, unequal-variance t tests. RESULTS: Mean OSCE scores for the 8-week and 6-week curricula were not statistically different. Mean NBME scores also did not statistically differ. Six-week students performed significantly better in the specific OSCE subdomains of blood pressure, orthostatic blood pressure, rectal exam, and fecal occult blood test. CONCLUSIONS: Overall OSCE and NBME exam performance did not differ between 8-week and 6-week surgery clerkship students. PMID- 24238601 TI - Structure and function of the human skin microbiome. AB - An abundant and diverse collection of bacteria, fungi, and viruses inhabits the human skin. These microorganisms vary between individuals and between different sites on the skin. The factors responsible for the unique variability of the skin microbiome are only partly understood, but results suggest that host genetic and environmental influences play a major role. Today, the steady accumulation of data describing the skin microbiome, combined with experiments designed to test the biological functions of surface microbes, has provided new insights into links between human physiology and skin microbiota. This review describes some of the current information regarding the skin microbiome and its impact on human health. Specifically, we summarize the present understanding of the function of microbe-host interactions on the skin and highlight some unique features that distinguish skin commensal organisms from pathogenic microbes. PMID- 24238604 TI - The relationship between grit and resident well-being. AB - BACKGROUND: The well-being of residents in general surgery is an important factor in their success within training programs. Consequently, it is important to identify individuals at risk for burnout and low levels of well-being as early as possible. The aim of this study was to test the hypothesis that resident well being may be related to grit, a psychological factor defined as perseverance and passion for long-term goals. METHODS: One hundred forty-one residents across 9 surgical specialties at 1 academic medical center were surveyed; the response rate was 84%. Perseverance was measured using the Short Grit Scale. Resident well being was measured with (1) burnout using the Maslach Burnout Inventory and (2) psychological well-being using the Dupuy Psychological General Well-Being Scale. RESULTS: Grit was predictive of later psychological well-being both as measured by the Maslach Burnout Inventory (B = -.20, P = .05) and as measured by the Psychological General Well-Being Scale (B = .27, P < .01). CONCLUSIONS: Measuring grit may identify those who are at greatest risk for poor psychological well being in the future. These residents may benefit from counseling to provide support and improve coping skills. PMID- 24238606 TI - Anti-phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis. AB - AIM: To identify a novel autoantibody specific to autoimmune hepatitis (AIH) and to evaluate its clinical significance. METHODS: Non-nuclear component protein extracted from normal human liver cell CyrohNHpes cultures that reacted with sera from AIH patients on a western blot was identified as an antigenic protein and subjected to N-terminal amino acid analysis to identify phosphoenolpyruvate carboxykinase 2 (PCK2). Enzyme-linked immunoassay (ELISA) for anti-PCK2 antibody was conducted on sera samples from patients with AIH (n = 42), primary biliary cirrhosis (PBC; n = 48), non-alcoholic steatohepatitis (NASH, n = 41), chronic hepatitis C (CHC, n = 20), drug-induced liver injury (DILI, n = 10), systemic lupus erythematosus (SLE, n = 16) and on sera samples from healthy volunteers (n = 30). Clinical findings were compared for AIH patients testing positive and negative for anti-PCK2 antibody. RESULTS: ELISA findings showed that mean anti PCK2 antibody titer in sera from AIH patients was significantly higher than in PBC, NASH, CHC, DILI and SLE patients, as well as in healthy volunteers. Anti PCK2 antibody was present in 50.0% (21/42) of AIH, 14.6% (7/48) of PBC, 4.9% (2/41) of NASH, and 10.0% (2/20) of CHC patients, 0% (0/10) of DILI, 12.5% (2/16) of SLE and in 3.3% (1/30) of healthy volunteers. The sensitivity, specificity and accuracy of using the detection of anti-PCK2 antibody in diagnosing AIH were 50.0%, 91.5% and 83.1%, respectively. None of the AIH patients positive for anti PCK2 antibody showed characteristic clinical features. CONCLUSION: Although further investigations into the clinical usefulness are necessary, anti-PCK2 may have potential as a diagnostic marker for AIH. PMID- 24238607 TI - Morphological priming in child German. AB - Regular and irregular inflection in children's production has been examined in many previous studies. Yet, little is known about the processes involved in children's recognition of inflected words. To gain insight into how children process inflected words, the current study examines regular -t and irregular -n participles of German using the cross-modal priming technique testing 108 monolingual German-speaking children in two age groups (group I, mean age: 8;4, group II, mean age: 9;9) and a control group of 72 adults. Although both age groups of children had the same full priming effect as adults for -t forms, only children of age group II showed an adult-like (partial) priming effect for -n participles. We argue that children (within the age range tested) employ the same mechanisms for regular inflection as adults but that the lexical retrieval processes required for irregular forms become more efficient when children get older. PMID- 24238605 TI - Reasons for institutionalization of people with dementia: informal caregiver reports from 8 European countries. AB - OBJECTIVES: To explore reasons for institutionalization of people with dementia according to informal caregivers as well as variation in reasons between countries. DESIGN: An explorative cross-sectional study was conducted in 8 European countries. SETTING: Per country, a minimum of 3 long term care facilities, offering care and accommodation as a package, participated in this study. Participating countries were selected to represent different geographic areas in Europe. PARTICIPANTS: Of the 791 informal caregivers involved in the RightTimePlaceCare project of people with dementia who were recently admitted to a long term care facility, 786 were included for this study. MEASUREMENTS: As part of a semistructured interview, informal caregivers were asked the main reason for institutionalization in an open-ended question. Answers were categorized according to a conventional coding approach. All reasons were then quantified and tested. RESULTS: Mainly patient-related reasons were stated, such as neuropsychiatric symptoms (25%), care dependency (24%), and cognition (19%). Neuropsychiatric symptoms were among the most often mentioned reasons in most countries. Besides patient-related reasons, caregiver burden and the inability of the informal caregiver to care for the patient were stated as reasons (both 15%). Further analyses showed countries differ significantly in reasons according to informal caregivers. Additionally, reasons were analyzed for spouses and child caregivers, showing that spouses more often stated reasons related to themselves compared with child-caregivers. CONCLUSION: Multiple reasons contribute to the institutionalization for people with dementia, with several factors that may influence why there were country differences. Variation in the organization of dementia care and cultural aspects, or the relationship between the informal caregiver and person with dementia may be factors influencing the reasons. Because of a wide variation in reasons between countries, no one-size-fits-all approach can be offered to guide informal caregivers when facing the possibility of institutionalization of the person with dementia. PMID- 24238608 TI - Sperm mitochondria in reproduction: good or bad and where do they go? AB - The mitochondrion is the major energy provider to power sperm motility. In mammals, aside from the nuclear genome, mitochondrial DNA (mtDNA) also contributes to oxidative phosphorylation to impact production of ATP by coding 13 polypeptides. However, the role of sperm mitochondria in fertilization and its final fate after fertilization are still controversial. The viewpoints that sperm bearing more mtDNA will have a better fertilizing capability and that sperm mtDNA is actively eliminated during early embryogenesis are widely accepted. However, this may be not true for several mammalian species, including mice and humans. Here, we review the sperm mitochondria and their mtDNA in sperm functions, and the mechanisms of maternal mitochondrial inheritance in mammals. PMID- 24238609 TI - Generation of hematopoietic stem cells from purified embryonic endothelial cells by a simple and efficient strategy. AB - Recent progress by versatile approaches supports the new hypothesis that multi potent hematopoietic stem cells (HSCs) are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to-hematopoietic transition (EHT). Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DL1-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 (E10.5) Tie2(+) cells remarkably. Then, the immunophenotypically defined endothelial cells were harvested by a combination of surface markers (Flk1(+)CD31(+)CD41(-)CD45(-)Ter119(-)) from the caudal half of E10.0-E11.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co cultures led to long-term, high-level, multi-lineage, and multi-organ hematopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at E10.5, and a significant increase was detected at E11.0, which suggests a temporally specific regulation. Taken together, for the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research. PMID- 24238610 TI - Sequence diversity and enzyme activity of ferric-chelate reductase LeFRO1 in tomato. AB - Ferric-chelate reductase which functions in the reduction of ferric to ferrous iron on root surface is a critical protein for iron homeostasis in strategy I plants. LeFRO1 is a major ferric-chelate reductase involved in iron uptake in tomato. To identify the natural variations of LeFRO1 and to assess their effect on the ferric-chelate reductase activity, we cloned the coding sequences of LeFRO1 from 16 tomato varieties collected from different regions, and detected three types of LeFRO1 (LeFRO1(MM), LeFRO1(Ailsa) and LeFRO1(Monita)) with five amino acid variations at the positions 21, 24, 112, 195 and 582. Enzyme activity assay revealed that the three types of LeFRO1 possessed different ferric-chelate reductase activity (LeFRO1(Ailsa) > LeFRO1(MM) > LeFRO1(Monita)). The 112th amino acid residue Ala of LeFRO1 is critical for maintaining the high activity of ferric-chelate reductase, because modification of this amino acid resulted in a significant reduction of enzyme activity. Further, we showed that the combination of the amino acid residue Ile at the site 24 with Lys at the site 582 played a positive role in the enzyme activity of LeFRO1. In conclusion, the findings are helpful to understand the natural adaptation mechanisms of plants to iron limiting stress, and may provide new knowledge to select and manipulate LeFRO1 for improving the iron deficiency tolerance in tomato. PMID- 24238611 TI - MYPT1 sustains centromeric cohesion and the spindle-assembly checkpoint. PMID- 24238612 TI - Characterization and fine mapping of Glabrous rice 2 in rice. PMID- 24238613 TI - German translation of the Alberta Context Tool and two measures of research use: methods, challenges and lessons learned. AB - BACKGROUND: Understanding the relationship between organizational context and research utilization is key to reducing the research-practice gap in health care. This is particularly true in the residential long term care (LTC) setting where relatively little work has examined the influence of context on research implementation. Reliable, valid measures and tools are a prerequisite for studying organizational context and research utilization. Few such tools exist in German. We thus translated three such tools (the Alberta Context Tool and two measures of research use) into German for use in German residential LTC. We point out challenges and strategies for their solution unique to German residential LTC, and demonstrate how resolving specific challenges in the translation of the health care aide instrument version streamlined the translation process of versions for registered nurses, allied health providers, practice specialists, and managers. METHODS: Our translation methods were based on best practices and included two independent forward translations, reconciliation of the forward translations, expert panel discussions, two independent back translations, reconciliation of the back translations, back translation review, and cognitive debriefing. RESULTS: We categorized the challenges in this translation process into seven categories: (1) differing professional education of Canadian and German care providers, (2) risk that German translations would become grammatically complex, (3) wordings at risk of being misunderstood, (4) phrases/idioms non-existent in German, (5) lack of corresponding German words, (6) limited comprehensibility of corresponding German words, and (7) target persons' unfamiliarity with activities detailed in survey items. Examples of each challenge are described with strategies that we used to manage the challenge. CONCLUSION: Translating an existing instrument is complex and time-consuming, but a rigorous approach is necessary to obtain instrument equivalence. Essential components were (1) involvement of and co-operation with the instrument developers and (2) expert panel discussions, including both target group and content experts. Equivalent translated instruments help researchers from different cultures to find a common language and undertake comparative research. As acceptable psychometric properties are a prerequisite for that, we are currently carrying out a study with that focus. PMID- 24238614 TI - Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats. AB - BACKGROUND: Testosterone deficiency is associated with insulin resistance. However, how testosterone deficiency affects insulin actions remains unclear. The aim of this study was to investigate the influence of castration-induced testosterone deficiency on the metabolic kinetics of glucose and to evaluate the hepatic and extra-hepatic insulin sensitivity, in advanced-age male Sprague Dawley (SD) rats. METHODS: Ten-week-old male SD rats were randomly divided into three groups: (1) a control group (n = 10) in which the rats underwent sham castration (2) a castrated group (TD group for testosterone deficiency, n = 10) in which the rats underwent bilateral orchidectomy surgery and (3) a castrated group given testosterone propionate via intraperitoneal injection (25 mg/kg/day) to supplement androgen (TD + TP group, n = 10). At ten weeks after castration in the noted groups, all rats were subjected to an oral glucose tolerance test (OGTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Twenty weeks following that treatment, all rats underwent a hyperinsulinemic euglycemic clamp procedure in conjunction with isotope--labeled glucose and glycerol tracer infusions. The rate of appearance (Ra) of glucose, glycerol and gluconeogenesis (GNG), hepatic glucose production and the rate of glucose disappearance (Rd) were assessed. Glucose uptake was determined by measuring the 2-deoxy-D-14C-glucose in the gastrocnemius muscles. RESULTS: Ten weeks after castration in the TD group, the fasting blood glucose and insulin levels were significantly increased (p < 0.01), the glucose-- induced insulin secretion was impaired and ITT revealed a temporarily increased whole body insulin sensitivity compared with the control group; 30 weeks after castration, the Ra of glucose, Ra of glycerol, as well as the HGP and GNG were also increased (p < 0.01), while the exogenous glucose infusion rate and uptake glucose in the muscle markedly decreased (p < 0.01). CONCLUSIONS: Castration-induced testosterone deficiency primarily increases fasting blood glucose levels. The clamp experiments revealed a clear insulin resistance both at the hepatic and extra-hepatic levels. PMID- 24238615 TI - Cocaine withdrawal influences paternal behavior and associated central expression of vasopressin, oxytocin and tyrosine hydroxylase in mandarin voles. AB - Although the disruptive effects of cocaine on the maternal care are well known, little is known about paternal care in the context of cocaine abuse. Vasopressin (AVP), oxytocin (OT) and dopamine (DA) have been found to regulate paternal behavior and are also involved in cocaine abuse. Mandarin voles (Microtus mandarinus) are socially monogamous and display high levels of paternal care. Here, we investigated whether paternal behavior and associated central levels of AVP, OT and DA were altered following 24 h of withdrawal from 4 day administration of 20 mg/kg/day cocaine. Our data shows that vole fathers did not experience altered levels of locomotion during an open field test. However, compared to controls, cocaine attenuated licking/grooming and contact behavior and shortened the latency to crouching, contact and pup retrieval. Last, fewer AVP and OT immunoreactive neurons in the paraventricular nucleus and more tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area were observed in cocaine-treated fathers. These results indicate that cocaine withdrawal disturbs the expression of partial paternal behavior by altering central levels of AVP, OT and DA. PMID- 24238617 TI - A simplified mathematical model for thrombin generation. AB - A new phenomenological mathematical model based directly on laboratory data for thrombin generation and having a patient-specific character is described. A set of the solved equations for cell-based models of blood coagulation that can reproduce the temporal evolution of thrombin generation is proposed; such equations are appropriate for use in computational fluid dynamic (CFD) simulations. The initial values for the reaction rates are either taken from already existing model or experimental data, or they can obtained from simple reasoning under certain assumptions; it is shown that coefficients can be adjusted in order to fit a range of different thrombin generation curves as derived from thrombin generation assays. The behaviour of the model for different platelet concentration seems to be in good agreement with reported experimental data. It is shown that the reduced set of equations used represents to a good approximation a low-order model of the detailed mechanism and thus it can represent a cost-effective and-case specific mathematical model of coagulation reactions up to thrombin generation. PMID- 24238616 TI - Effects of rabbit anti-alpha-melanocyte-stimulating hormone (alpha-MSH) immunoglobulins on alpha-MSH signaling related to food intake control. AB - Anti-alpha-melanocyte-stimulating hormone (alpha-MSH) polyclonal antibodies have been used for alpha-MSH neutralization in functional studies, but the results are sometime inconsistent with the antibody expected blocking properties. The present study aimed to determine if rabbit (Rb) anti-alpha-MSH immunoglobulins (Ig) may inhibit or enhance alpha-MSH signaling on melanocortin receptor type 4 (MC4R) and alpha-MSH-induced anorexigenic effect if presented as immune complexes with alpha MSH. Polyclonal Rb anti-alpha-MSH IgG were commercially available and their ability to bind alpha-MSH has been confirmed by the immunohistochemical detection of alpha-MSH neurons in the rat hypothalamus. In vitro assay of the cyclic adenosine mono-phosphate (cAMP) secreted by cells transfected with MC4R was performed to analyze effect of Rb IgG on alpha-MSH-induced cAMP production. We found that adding Rb IgG to alpha-MSH resulted in stimulation of cAMP detected at lower peptide concentrations as compared to alpha-MSH alone. To determine effects of Rb IgG on food intake, rats were injected into the arcuate hypothalamic nucleus with either alpha-MSH, Rb IgG alone or Rb IgG preincubated with alpha MSH. During 2 days after injections, food intake was increased in both groups of rats receiving Rb IgG. However, during following 4 days when food was restricted to 1h/day, only the Rb IgG group displayed higher food intake. Furthermore, after the refeeding, 24h food intake was lower in rats receiving Rb IgG - alpha-MSH immune complexes. This group of rats was also characterized by higher number of immunopositive neurons in the arcuate nucleus expressing alpha-MSH and agouti related protein but not tyrosine hydroxylase. Taken together, these results show that Rb anti-alpha-MSH antisera, although efficient for immunohistochemical detection of alpha-MSH, does not always display alpha-MSH blocking properties but, in contrast, may enhance alpha-MSH binding to MC4R and increase alpha-MSH anorexigenic effects when presented as immune complexes with the peptide. PMID- 24238618 TI - Variability of the autoregulation index decreases after removing the effect of the very low frequency band. AB - Dynamic cerebral autoregulation (dCA) estimates show large between and within subject variability. Sources of variability include low coherence and influence of CO2 in the very low frequency (VLF) band, where dCA is active. This may lead to unreliable transfer function and autoregulation index (ARI) estimates. We tested whether variability of the ARI could be decreased by suppressing the effect of the VLF band through filtering. We also evaluated whether filtering had any effect on mean group differences between healthy subjects and acute stroke patients. Data from a recent mobilization stroke study were re-analyzed. Middle cerebral artery cerebral blood flow velocity (MCA-CBFV), mean arterial blood pressure (MABP) and end tidal PCO2 (PetCO2) were obtained in 16 healthy subjects and 27 acute ischemic stroke patients in the supine position. The ARI index was calculated from the transfer function (TF) by using spontaneous BP fluctuations. Three different filtering strategies were compared; no filtering (NF), a high pass filter at 0.04 Hz (Time Domain Filtering: TDF) and a high pass Transfer Function Filter (TFF) at 0.04 Hz. In addition, a simulation study was done to obtain further insight into the effects of the applied filters. The variability of the ARI index decreased significantly only with TFF in healthy subjects (standard deviation (left vs. right) after NF 2.28 vs. 2.36, after TDF 2.13 vs. 2.31 after TFF 1.09 vs. 1.19, p<0.001). Variability was not significantly reduced in stroke patients. The mean ARI was significantly lower in stroke patients compared to healthy subjects after TFF (affected hemisphere 5.85+/-1.96 vs. 7.13+/-1.09, non-affected hemisphere 5.96+/-1.64 vs. 7.31+/-1.19, p<0.01 for both hemispheres), but not after NF or TDF. The simulation study showed that TFF results in an overestimation of the ARI index at low ARI levels (0-3), but in correct estimates at higher ARI levels. Removing the effect of the VLF band with TFF results in less ARI variability in healthy subjects, and in more pronounced group differences between stroke patients and healthy subjects. This will improve diagnostic properties when using TFA for ARI calculation. PMID- 24238619 TI - Agreement between patient-reported and doctor-reported patient intervals and date of first symptom presentation in cancer diagnosis - a population-based questionnaire study. AB - BACKGROUND: The concept of delay in cancer diagnosis has been a scientific issue for decades, and there is still no standardised and validated way to measure the time intervals. One of the intervals that are difficult to measure is the patient interval (i.e. the period from the patient's first symptom until the first presentation to the health care system) because dates of symptom onset and first presentation are difficult to establish precisely. Further, since patients may have another experience of the diagnostic pathway than e.g. the general practitioner (GP), a reasonable question remains whether patients and GPs agree on these important milestones. The objective of this study was to analyse the agreement between patient-reported and GP-reported patient intervals and date of first presentation of cancer-related symptom(s) to the GP. METHODS: On the basis of a cohort study, we included incident cancer patients from the former Aarhus County from 1 September, 2004 to 31 August, 2005. Both patients and GPs reported the length of the patient interval and the date of the first presentation to the GP with a cancer-related symptom measured by self-administered questionnaires. Agreement was measured using agreement-survival plots and Lin's concordance correlation coefficient (CCC). RESULTS: There was full agreement between GP- and patient-reported patient intervals in 21.0% of all the cancer cases. In 50.1% of cases, patients and GPs agreed about the patient interval within a margin of one month. There was full agreement between GP- and patient-reported date of first presentation in 37.5% of the cancer cases and within one week in 52.0% of all the cancer cases. Overall, the agreement on the length of the patient interval was poor (CCC=0.513), but better for patients presenting with alarm symptoms. The agreement was moderate between GP- and patient-reported dates of first presentation (CCC=0.924). CONCLUSION: We found that GPs systematically reported a longer patient interval than patients did. We found moderate agreement on reported date of first presentation of symptoms to the GP, meaning that the disagreement in reported patient interval is related to date of first symptom rather than date of first presentation to the GP. PMID- 24238621 TI - Keloid of the toe: Novel pressure treatment. PMID- 24238620 TI - ET-1-induced growth promoting responses involving ERK1/2 and PKB signaling and Egr-1 expression are mediated by Ca2+/CaM-dependent protein kinase-II in vascular smooth muscle cells. AB - Endothelin-1 (ET-1), a potent vasoactive peptide with a pathogenic role in vascular diseases, has been shown to induce the activation of ERK1/2, PKB and the expression of a transcriptional regulator, the early growth response 1 (Egr-1), key mediators of hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). We have demonstrated earlier that ET-1 requires H2O2 generation to activate these signaling pathways and Ca2+, calmodulin (CaM) and Ca2+/CaM-dependent protein kinase II (CaMKII), play a critical role to trigger H2O2-induced effects in VSMC. However, an involvement of CaMKII in mediating ET-1 induced responses in VSMC remains unknown. Therefore, by utilizing pharmacological inhibitors of CaM, CaMKII, a CaMKII inhibitor peptide and CaMKII knockdown techniques, we have investigated the contribution of CaM and CaMKII in ET-1-induced ERK1/2 and PKB signaling, Egr-1 expression and hypertrophic and proliferative responses in VSMC. W-7 and calmidazolium, antagonists of CaM, as well as KN-93, an inhibitor of CaMKII activity, attenuated ET-1-induced ERK1/2 and PKB phosphorylation. In addition, transfection of VSMC with a CaMKII inhibitory peptide suppressed ET-1-evoked ERK1/2 and PKB phosphorylation. Similarly, siRNA-mediated CaMKII silencing reduced ET-1-produced ERK1/2 and PKB phosphorylation. CaM and CaMKII blockade also significantly lowered the ET-1 induced protein and DNA synthesis as well as Egr-1 expression. These findings demonstrate that CaMKII plays a critical role in ET-1-induced growth promoting signaling pathways as well as hypertrophic and proliferative responses in VSMC. PMID- 24238622 TI - Detrimental effect of cypermethrin treated nets on Culicoides populations (Diptera; Ceratopogonidae) and non-targeted fauna in livestock farms. AB - Bluetongue (BT) is an important disease of ruminants which exhibits its most severe clinical signs on cattle and especially on certain breeds of sheep. The known vectors of BT are small insects of the genus Culicoides (Diptera; Ceratopogonidae). Two species from this genus - Culicoides imicola and Culicoides obsoletus - play the major role in the transmission of the disease in Europe. Several prophylactic methods are used to avoid transmission; however, an easy and cost-effective preventive technique would be very useful for the control of the Culicoides populations near the animals. In the present study, the insecticide effect of cypermethrin treated nets on a Culicoides population was evaluated. A polyethylene net sprayed with 1L cypermethrin solution (1%) surrounding a UV light suction trap was placed at a cattle farm in Majorca (Balearic Islands). Collections of Culicoides and other fauna from the trap and floor around the net were compared with a control. Results showed no significant differences in the collection of Culicoides midges between the insecticide-treated net and the control. However, significant differences were observed in the collection of the non-target fauna between the treated net and the control, indicating that the dose used in the present trial was enough to kill most of the arthropods that contacted the net. The reasons for these equivocal findings and means to improve this technique for the control of Culicoides midges are discussed. PMID- 24238623 TI - Enteromyxum leei infection in parrotfish, Sparisoma cretense: histopathological, morphological and molecular study. AB - Enteromyxum leei (Myxozoa) has been identified as the aetiological agent of morbidity and mortality in captive feral parrotfish, Sparisoma cretense held at the facilities of Cretaquarium, the public aquarium of the Hellenic Centre for Marine Research in Crete. The parasite caused substantial mortality to the parrotfish exceeding 60% over a period of 3.5 months. Here we describe the course of disease, the effects of the parasite on the host based on histopathological observations and we provide morphological and molecular data on the parasite. PMID- 24238624 TI - Anemia amelioration by lactose infusion during trypanosomosis could be associated with erythrocytes membrane de-galactosylation. AB - African trypanosomosis is a potentially fatal disease that is caused by extracellular parasitic protists known as African trypanosomes. These parasites inhabit the blood stream of their mammalian hosts and produce a number of pathological features, amongst which is anemia. Etiology of the anemia has been partly attributed to an autoimmunity-like mediated erythrophagocytosis of de sialylated red blood cells (dsRBCs) by macrophages. Lactose infusion to infected animals has proven effective at delaying progression of the anemia. However, the mechanism of this anemia prevention is yet to be well characterized. Here, the hypothesis of a likely induced further modification of the dsRBCs was investigated. RBC membrane galactose (RBC m-GAL) and packed cell volume (PCV) were measured during the course of experimental trypanosomosis in mice infected with Trypanosoma congolense (stb 212). Intriguingly, while the membrane galactose on the RBCs of infected and lactose-treated mice (group D) decreased as a function of parasitemia, that of the lactose-untreated infected group (group C) remained relatively constant, as was recorded for the uninfected lactose-treated control (group B) animals. At the peak of infection, the respective cumulative percent decrease in PCV and membrane galactose were 30 and 185 for group D, and 84 and 13 for group C. From this observed inverse relationship between RBCs membrane galactose and PCV, it is logical to rationalize that the delay of anemia progression during trypanosomosis produced by lactose might have resulted from an induction of galactose depletion from dsRBCs, thereby preventing their recognition by the macrophages. PMID- 24238627 TI - [Use of the simulation in the clinical investigation]. PMID- 24238625 TI - Alcohol consumption is inversely associated with stage 3 chronic kidney disease in middle-aged Taiwanese men. AB - BACKGROUND: Chronic kidney disease (CKD) is a major global public health burden, but there is limited understanding of the relationship of alcohol consumption with CKD. METHODS: In this cross-sectional multivariable study, all participants of a health check-up program in Ditmanson Medical Foundation Chia-Yi Christian Hospital in Taiwan from 2003 to 2009 (15,353 women and 11,900 men) were included for analysis. Estimated glomerular filtration rate was used to define CKD stage and history of alcohol consumption was obtained by self-reporting. Multivariable logistic regression analyses of gender-specific association of alcohol drinking with stage 3 CKD were conducted. A trend tests was conducted to check the dose response relationship of alcohol consumption with renal disease. A sensitivity test was conducted to rule out the likelihood of reverse causality. RESULTS: The prevalence of stage 3 CKD was lower in drinkers than non-drinkers (p < 0.001) and the percentage of drinkers with stage 3 CKD was less than that of non-drinkers. Multivariable analysis indicated that alcohol consumption was negatively associated with the presence of stage 3 CKD in men (adjusted odds ratio [aOR] for occasional drinking: 0.68, 95% CI: 0.59 ~ 0.78, p < 0.001; aOR for frequent drinking: 0.47, 95% CI: 0.35 ~ 0.63, p < 0.001). Advanced age, hypertension, anemia, BMI of at least 24, hyperuricemia, and proteinuria were also associated with stage 3 CKD in men. Trend tests indicated lower odds of having stage 3 CKD with increased alcohol consumption in both genders. Subgroup analyses and sensitivity tests also indicated the reverse association between alcohol consumption and stage 3 CKD in men regardless of age, diabetes status, and other risky behaviors. CONCLUSIONS: Alcohol consumption was inversely associated with stage 3 CKD in Taiwanese men. However, considering the potential of other health damage with alcohol consumption, the current results should be interpreted cautiously. PMID- 24238626 TI - Parental report of receipt of adolescent preventive health counseling services from pediatric providers. AB - OBJECTIVE: Little is known about prevention-focused counseling health providers deliver to parents of adolescents. This study compared parental report of discussions with their adolescents' providers about a range of adolescent prevention topics. METHODS: Between June and November 2009, a questionnaire was provided to parents accompanying adolescents aged 11-18 on outpatient clinic visits. Parents indicated, anonymously, which of 22 prevention topics they remembered discussing with their adolescent's provider. Hierarchical logistic regression models were used to identify correlates of parental recall. RESULTS: Among the 358 participants, 83% reported discussing at least one prevention topic. More parents reported discussing general prevention topics than mental health or high-risk topics (e.g. sex). Adolescent gender, visit type, having a usual source of care, and parental beliefs about their adolescents' risk behaviors correlated with parental report of discussions about high-risk and mental health topics. CONCLUSION: Most parents recalled discussing one or more topics with their adolescent's health provider. However, parental report of discussions about topics linked to significant adolescent morbidity was low. PRACTICE IMPLICATIONS: Strategies to improve the frequency, timeliness and appropriateness of counseling services delivered to parents about adolescent preventive health are needed. Strategies that utilize decision support tools or patient education tools may be warranted. PMID- 24238628 TI - Radiation protection for an intraoperative X-ray source compared to C-arm fluoroscopy. AB - BACKGROUND: Intraoperative radiotherapy (IORT) using the INTRABEAM((r)) system promises a flexible use regarding radiation protection compared to other approaches such as electron treatment or HDR brachytherapy with (192)Ir or (60)Co. In this study we compared dose rate measurements of breast- and Kypho IORT with C-arm fluoroscopy which is needed to estimate radiation protection areas. MATERIALS AND METHODS: C-arm fluoroscopy, breast- and Kypho-IORTs were performed using phantoms (silicon breast or bucket of water). Dose rates were measured at the phantom's surface, at 30 cm, 100 cm and 200 cm distance. Those measurements were confirmed during 10 Kypho-IORT and 10 breast-IORT patient treatments. RESULTS: The measured dose rates were in the same magnitude for all three paradigms and ranges from 20 MUSv/h during a simulated breast-IORT at two meter distance up to 64 mSv/h directly at the surface of a simulated Kypho-IORT. Those measurements result in a circle of controlled area (yearly doses >6 mSv) for each paradigm of about 4 m+/-2 m. DISCUSSION/CONCLUSIONS: All three paradigms show comparable dose rates which implies that the radiation protection is straight forward and confirms the flexible use of the INTRABEAM((r)) system. PMID- 24238629 TI - Marginal costing methods highlight the contributing cost of comorbid conditions in Medicare patients: a quasi-experimental case-control study of ischemic stroke costs. AB - BACKGROUND: Cost of illness studies are needed to provide estimates for input into cost-effectiveness studies and as information drivers to resource allocation. However, these studies often do not differentiate costs associated with the disease of interest and costs of co-morbidities. The goal of this study was to identify the 1-year cost of ischemic stroke compared to the annual cost of care for a comparable non-stroke group of South Carolina (SC) Medicare beneficiaries resulting in a marginal cost estimate. METHODS: SC data for 2004 and 2005 were used to estimate the mean 12 month cost of stroke for 2,976 Medicare beneficiaries hospitalized for Ischemic Stroke in 2004. Using nearest neighbor propensity score matching, a control group of non-stroke beneficiaries were matched on age, gender, race, risk factors, and Charlson comorbidity index and their costs were calculated. Marginal cost attributable to ischemic stroke was calculated as the difference between these two adjusted cost estimates. RESULTS: The total cost estimated for SC stroke patients for 1 year (2004) was $81.3 million. The cost for the matched comparison group without stroke was $54.4 million. Thus, the 2004 marginal costs to Medicare due to Ischemic stroke in SC are estimated to be $26.9 million. CONCLUSIONS: Accurate estimates of cost of care for conditions, such as stroke, that are common in older patients with a high rate of comorbid conditions require the use of a marginal costing approach. Over estimation of cost of care for stroke may lead to prediction of larger savings than realizable from important stroke treatment and prevention programs, which may damage the credibility of program advocates, and jeopardize long term funding support. Additionally, correct cost estimates are needed as inputs for valid cost-effectiveness studies. Thus, it is important to use marginal costing for stroke, especially with the increasing public focus on evidence-based economic decision making to be expected with healthcare reform. PMID- 24238630 TI - Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial. AB - BACKGROUND: Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified. METHODS/DESIGN: This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self esteem, quality of life, and social contacts. In addition, the participants' motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs. DISCUSSION: This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified. TRIAL REGISTRATION: The protocol for this study is registered with the Netherlands Trial Registry NTR2415. PMID- 24238632 TI - Abstracts of the UK Stroke Forum 2013 Conference. December 3-5, 2013. Harrogate, North Yorkshire, United Kingdom. PMID- 24238631 TI - Alterations in phosphorylated cAMP response element-binding protein (pCREB) signaling: an endophenotype of lithium-responsive bipolar disorder? AB - OBJECTIVES: Abnormalities of signal transduction are considered among the susceptibility factors for bipolar disorder (BD). These include changes in G protein-mediated signaling and subsequent modification of gene expression via transcription factors such as cAMP response element-binding protein (CREB). METHODS: We investigated levels of CREB in lymphoblasts from patients with BD, all responders to lithium prophylaxis (n = 13), and healthy control subjects (n = 15). Phosphorylated CREB (pCREB) was measured by immunoblotting in subjects with BD (n = 15) as well as in their affected (n = 17) and unaffected (n = 18) relatives, and healthy controls (n = 16). RESULTS: Basal CREB levels were comparable in patients and control subjects and were not changed by lithium treatment. pCREB levels were increased in both patients and their relatives compared to controls (p = 0.003). Forskolin stimulation led to a 24% increase in pCREB levels in cells from healthy subjects (p = 0.002) but not in the other three groups. When using basal and stimulated pCREB levels as a biochemical phenotype in a preliminary linkage study, we found the strongest support for linkage in regions largely overlapping with those showing linkage with the clinical phenotype (3p, 6p, 16p, 17q, 19q, and 21q). CONCLUSIONS: Abnormal pCREB signaling could be considered a biochemical phenotype for lithium-responsive BD. PMID- 24238633 TI - Early response to chemotherapy as an indicator for the management of germinoma like tumors of the pineal and/or suprasellar regions. AB - Recent advances in diagnostic imaging and experience with germinomas may allow for the differentiation of central nervous system germinomas from other tumors based on clinical information, without histological verification. We retrospectively analyzed clinically diagnosed germinoma-like tumors of the pineal and/or suprasellar regions. This was done to evaluate the efficacy of our strategy of defining germinoma-compatible tumors based on good responses to initial chemotherapy. The responses to chemotherapy and survival of 34 consecutive patients with germinoma-like tumors who underwent initial treatment from July 2001 to October 2010 were analyzed. The minimum apparent diffusion coefficient (minADC) value and proton magnetic resonance spectroscopy (MRS) were evaluated in recent patients. Twelve patients with histologically verified germinomas and 18 with germinoma-compatible tumors showed early logarithmic decreases in tumor volume in response to initial chemotherapy, typical low minADC values and typical MRS characteristics, including increased choline/creatine ratios, decreased N-acetylasparate/creatine ratios, and large lipid peaks. These patients had good progression-free survival. The other four patients, with histologically verified non-germinomas, showed no response to chemotherapy, and one patient with a pineoblastoma showed a similar minADC value and MRS characteristics to those of patients with germinomas. The response to initial chemotherapy can be used to distinguish germinoma-compatible tumors from non germinoma in patients with germinoma-like tumors of the pineal and/or suprasellar regions. The evaluation of minADC and proton MRS are useful for distinguishing germinomas from other tumors. However, a subset of non-germinomas may show similar characteristics to germinomas. The benefit of bypassing unnecessary surgical intervention can be achieved, at least in Asian populations with a high incidence of germinomas. PMID- 24238634 TI - Evaluation of cerebrovascular reserve using xenon-enhanced CT scanning in patients with symptomatic middle cerebral artery stenosis. AB - Cerebrovascular reserve (CVR) is an important prognostic factor in patients with major cerebral arterial steno-occlusive disease. However, few studies have examined CVR in symptomatic intracranial stenosis without ipsilateral extracranial internal carotid artery stenosis. This study sought to evaluate CVR in patients with symptomatic middle cerebral artery (MCA) stenosis using xenon enhanced computed tomography (Xe/CT) with acetazolamide (ACZ) challenge. Twelve patients with symptomatic MCA stenosis were recruited. All patients were examined by Xe/CT to quantitatively measure resting cerebral blood flow (CBF) and received ACZ challenge to evaluate CVR. For resting CBF, no significant differences were found between the sides in four regions of interest. After the ACZ challenge test, the CVR was significantly different between hemispheres (ipsilateral versus contralateral CVR: 12.9 +/- 24.3% versus 28.0 +/- 16.8%, respectively; p=0.005) and in the MCA territory (ipsilateral versus contralateral CVR: 8.7 +/- 24.7% versus 29.3 +/- 24%, respectively; p=0.003). However, no significant differences in CVR were detected between cortical comparisons and white matter comparisons from the two sides. Thus, ACZ-challenge Xe/CT is useful for the measurement of CBF and CVR in these patients. Impaired CVR is an important characteristic of patients with symptomatic MCA stenosis. PMID- 24238635 TI - Remote cerebellar hemorrhage following supratentorial cerebrovascular surgery. AB - Three patients with remote cerebellar hemorrhage following supratentorial cerebrovascular surgery are presented. Remote cerebellar hemorrhage is a rare surgical complication that is most often associated with aneurysm clipping or temporal lobectomies. Bleeding occurs on the superior cerebellar cortex and is believed to be venous in origin. The precise pathogenesis of remote cerebellar hemorrhage has yet to be fully elucidated but is generally considered to be a consequence of intraoperative cerebrospinal fluid loss causing caudal displacement of the cerebellum with resultant stretching of the supracerebellar veins. This case series will hopefully shed further light on the incidence, presentation, workup, and treatment of this particular complication of supratentorial surgery. PMID- 24238636 TI - [Virtual library of Galicia]. PMID- 24238637 TI - Cell death pathways. PMID- 24238638 TI - Coding warnings without interfering with dismounted soldiers' missions. AB - OBJECTIVES: Warnings are an effective way to communicate hazard, yet they can also increase task demand when presented to operators involved in real-world tasks. Furthermore, in military-related tasks warnings are often given in codes to avoid counter-intelligence, which may foster additional working memory load. BACKGROUND: Adherence to warnings in the military domain is crucial to promote safety and reduce accidents and injuries. The empirical question arises as to how aspects of coding the warning may interfere with the primary task the individual is currently performing and vice versa. METHOD: Six experimental conditions were designed to assess how warning-code storage format, response format, and increasing working memory demand (retention) affected both performance on the primary task and the rate of compliance to warnings, considered here as the secondary task. RESULTS: Results revealed that the combination of warning-code storage and response format affected compliance rate and the highest compliance occurred when warnings were presented as pictorials and responses were coded verbally. Contrary to the proposed hypotheses, warning storage format did not affect performance on the primary task, which was only affected by the level of working memory demand. Thus, the intra-modal warning storages did not interfere with the visual/spatial nature of the primary operational task. However, increase in working memory demand, by increasing the number of memorized warning codes, had an effect on both compliance rate and primary task performance. CONCLUSIONS: Rather than warning code storage alone, it is the coupling of warning storage and response format that has the most significant effect on compliance. PMID- 24238639 TI - Dasatinib in combination with fludarabine in patients with refractory chronic lymphocytic leukemia: a multicenter phase 2 study. AB - Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti apoptotic regulators and restores fludarabine sensitivity in activated CLL. The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40mg/m2/day, days 1-3 every 28 day) for a total of 6 cycles in fludarabine refractory CLL. The primary endpoint was overall response rate according to the IWCLL'08 criteria. 20 patients were enrolled: 18 completed at least one cycle of treatment of which 67% finished at least 2 cycles of combination treatment. 3 of these 18 patients reached a formal PR (16.7%). Majority of patients obtained some reduction in lymph node (LN) size. Most frequent toxicity was related to myelosuppression. NF-kappaB RNA expression levels of circulating CLL cells decreased whereas the levels of pro-apoptotic NOXA increased during treatment. In conclusion, dasatinib/fludarabine combination has modest clinical efficacy in fludarabine-refractory patients. PMID- 24238640 TI - Validation of the revised international prognostic scoring system (IPSS-R) in patients with myelodysplastic syndrome: a multicenter study. AB - The revised IPSS (IPSS-R) was developed aiming at a better prognostication, taking into account patients treated with best supportive care. We herein validated this model on the basis of data from 1314 patients who received BSC only as well as patients who underwent induction chemotherapy (n=214) or allogeneic transplantation (n=167). We could demonstrate a clear distinction of the IPSS-R risk categories with regard to survival and risk of AML evolution in all patient cohorts. When comparing IPSS-R, IPSS, WHO prognostic scoring system (WPSS) and Duesseldorf score, the best results regarding the ability to predict survival were obtained by the IPSS-R. PMID- 24238641 TI - Penetrating defect of the ala nasi: combined reconstruction with a myocutaneous hinge- and paramedian forehead flap. PMID- 24238642 TI - Motion artifacts on coronary CT angiography images in patients with a pericardial effusion. AB - BACKGROUND: Patients with a pericardial effusion can have a pendulum-like movement of the heart. No reports associate the presence of pericardial fluid with coronary CT angiography (CTA) images that are degraded by motion artifact. OBJECTIVE: We tested the hypothesis that patients with pericardial effusion have coronary CTA images compromised by motion artifacts, even when other known causes of motion artifact in coronary imaging are minimized. METHODS: Among the prospectively electrocardiogram-gated single heart beat 320-detector row coronary CTA studies performed from September 2009 to May 2013, 13 consecutive studies acquired with a heart rate <60 beats/min that indicate a pericardial effusion formed an effusion cohort. A control cohort included 13 studies with no pericardial fluid performed by the same CT scanner; these were pair-matched to the effusion cohort for heart rate, sex, age, and body mass index. All studies were free of arrhythmia and respiratory motion. Motion artifact was separately assessed (3-point scale) at 8 coronary segments by 2 cardiovascular imaging teams. RESULTS: The mean pericardial effusion volume for the effusion cohort was 129 +/- 57 mL (range, 39-222 mL). Intra-observer/interobserver reproducibility of the motion artifact scores were good (kappa = 0.636-0.791). Motion artifacts were more frequently observed in the effusion cohort for the left circumflex (no, mild, severe artifact, 54%, 46%, 0% vs. 81%, 19%, 0%, respectively, for effusion vs. control; P = .039) and right coronary arteries (no, mild, severe artifact = 41%, 44% 15% vs. 79%, 21%, 0%, respectively, for effusion vs control; P < .001), especially for the middle or distal segments. Larger effusion volumes were associated with more severe motion artifacts. CONCLUSION: Patients with pericardial effusion have coronary CTA images compromised by cardiac motion artifacts, particularly in the left circumflex and right coronary arteries. PMID- 24238643 TI - Factors in the management of feeding in nursery school children as perceived by their mothers in rural Bondo County, Kenya. AB - BACKGROUND: The effects of malnutrition on health status and survival of children has been the subject of extensive research for several decades. Malnutrition affects physical growth, cognitive development of children, morbidity and mortality. The current study was an exploratory survey that focused on factors affecting feeding of nursery school children as perceived by their mothers in a rural setting in Usigu Division of Bondo County, Kenya. METHODS: The sampling frame was mothers whose children were in Kanyibok, Sanda and Usenge nursery schools. Purposive sampling methods were used to draw a total of 108 respondents. In a logistic regression model, bad management of feeding was the dependent variable while factors perceived to affect management of feeding were the independent variables. RESULTS: Married mothers were more likely to manage good feeding practices (OR, 0.34, 95% CI, 0.21-0.76; P = 0.022) relative to those who were single or widowed. Additional analyses showed that low education levels (OR, 7.33, 95% CI, 3.37-12.91; P = 0.023), younger mothers (OR, 6.04, 95% CI, 3.22 9.68; P = 0.029) and mothers engaged in business (OR, 4.02, 95% CI, 2.11-7.85; P = 0.027) increased their likelihood of not feeding the pre-school children. Majority of the children who ate the main meals in other houses belonged to young mothers in the age category of 15-29 years. Further analyses demonstrated that if the order of serving food was to the children first, then they had high likelihood of having good feeding relative to when the father was served first (OR, 0.22, 95% CI, 0.14-0.61; P = 0.011). CONCLUSIONS: Based on these findings, there is an urgent need for sensitization of the mothers on the management of feeding of these pre-school children in Bondo County. It is hoped that relevant interventions would then be designed with the view of managing children feeding in such rural settings as in Bondo County in Kenya. PMID- 24238644 TI - [Clinical stakes when switching from one antipsychotic to another]. AB - Switching antipsychotics is more and more common in our clinical practice. Several reasons can explain this observation. We have more and more antipsychotics available on the market with different receptor binding profiles and also different tolerability issues. Usually, the reasons of the switch are the following: insufficient efficacy or problems of tolerance (weight gain, metabolic disorders, extrapyramidal symptoms, hyperprolactinemia, sedation, sexual dysfunction). So that the switch takes place without complications, it is essential for the clinician to have full knowledge of both the receptor binding profiles of the antipsychotics in question and their half-life. The clinician has to expect a dopaminergic rebound when the introduced antipsychotic has a lesser affinity for the dopaminergic D2 receptor than that which is withdrawn or if it is a partial agonist with a particularly long half-life. On the other hand, a histaminergic or cholinergic rebound can be expected if the new antipsychotic has a lesser affinity for these two receptors. In all these scenarios, a "plateau" switch will often be recommended. Now, if a faster switch is imperative, various medication strategies exist to try to decrease the impact of the rebound effects. PMID- 24238645 TI - Dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis. AB - BACKGROUND: Dialysis disequilibrium syndrome is characterized by neurological symptoms resulting from cerebral edema, which occurs as a consequence of hemodialysis. Dialysis disequilibrium syndrome most often occurs in patients who have just started hemodialysis, during hemodialysis, or soon after hemodialysis; although it may also occur in patients who are under maintenance hemodialysis with pre-existing neurological disease. CASE PRESENTATION: A 70-year-old woman, who had been receiving maintenance hemodialysis for one year, was diagnosed with ovarian cancer by ascites cytological examination. Two years later, she reported severe headache and nausea during hemodialysis and was diagnosed with dialysis disequilibrium syndrome. Although brain images revealed mild hydrocephalus without any mass lesions, poorly differentiated adenocarcinoma cells were detected in her cerebrospinal fluid. These findings indicated that DDS was induced by neoplastic meningitis due to ovarian cancer metastasis. CONCLUSION: Neoplastic meningitis should be considered and excluded in hemodialysis patients with dialysis disequilibrium syndrome and malignancy by cytological examination of the cerebrospinal fluid even if cerebral imaging shows no obvious lesions. This is the first reported case of dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis. PMID- 24238646 TI - Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients. AB - BACKGROUND: Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. OBJECTIVES: The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. METHODS: Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT based asthma phenotypes. RESULTS: Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm(3) [SD, 112.6 mm(3)], 259.0 mm(3) [SD, 53.3 mm(3)], 366.4 mm(3) [SD, 195.3 mm(3)], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. CONCLUSIONS: Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. PMID- 24238647 TI - Correlation of increased PARP14 and CCL26 expression in biopsies from children with eosinophilic esophagitis. PMID- 24238648 TI - Is reconstruction the best management strategy for anterior cruciate ligament rupture? A systematic review and meta-analysis comparing anterior cruciate ligament reconstruction versus non-operative treatment. AB - AIMS: The purpose of this study was to determine the optimal clinical and cost effective strategy for managing people following ACL rupture. METHODS: A systematic review of the published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, psycINFO and the Cochrane Library) and unpublished literature (OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials and the UK National Research Register Archive) was conducted on April 2013. All randomised and non-randomised controlled trials evaluating clinical or health economic outcomes of isolated ligament reconstruction versus non-surgical management following ACL rupture were included. Methodological quality was assessed using the PEDro appraisal tool. When appropriate, meta-analysis was conducted to pool data. RESULTS: From a total of 943 citations, sixteen studies met the eligibility criteria. These included 1397 participants, 825 who received ACL reconstruction versus 592 who were managed non-surgically. The methodological quality of the literature was poor. The findings indicated that whilst reconstructed ACL offers significantly greater objective tibiofemoral stability (p<0.001), there appears limited evidence to suggest a superiority between reconstruction versus non-surgical management in functional outcomes. There was a small difference between the management strategies in respect to the development of osteoarthritis during the initial 20 years following index management strategy (Odds Ratio 1.56; p=0.05). CONCLUSIONS: The current literature is insufficient to base clinical decision-making with respect to treatment opinions for people following ACL rupture. Whilst based on a poor evidence, the current evidence would indicate that people following ACL rupture should receive non-operative interventions before surgical intervention is considered. PMID- 24238649 TI - Preliminary investigation of rate of torque development deficits following total knee arthroplasty. AB - BACKGROUND: To assess changes in maximal strength and rate of torque development (RTD) following TKA, and examine the relationships between these measures and physical function. METHODS: Thirty-five TKA patients and 23 controls completed isometric knee extensor torque testing preoperatively, 1, and 6 months after surgery. Maximal strength was calculated as the peak torque during a maximal voluntary isometric contraction (MVIC) of the knee extensor muscles, peak RTD (RTD(peak)) was calculated as the maximum value from the 1st derivative of the isometric knee extension torque data, RTD(25%) and RTD(50%) were calculated as the change in force over the change in time from force onset to 25% and 50% MVIC. Physical function was measured using a timed-up-and-go (TUG) and stair climbing test (SCT). RESULTS: RTD was significantly lower in the TKA group, at all-time points, compared to the Controls. MVIC and RTD significantly decreased 1-month following surgery (p=0.000 for all measures). RTD(peak) measures added to linear regressions with strength improved the prediction of TUG scores (p=0.006) and the SCT scores (p=0.015) 1-month post-surgery. Adding RTD(50%) to the regression model, following MVIC, improved predicting both TUG (p=0.033) and SCT (p=0.024). At 6-months, the addition of RTD(25%) to the regression model, following MVIC, improved the prediction of TUG (p=0.037) and SCT (p=0.036). CONCLUSION: Following TKA, physical function is influenced by both the maximal strength and the rate of torque development of the knee extensors, and the prediction of function is improved with the addition of RTD compared to that of maximal strength alone. PMID- 24238650 TI - The effect of tourniquet use on fixation quality in cemented total knee arthroplasty a prospective randomized clinical controlled RSA trial. AB - BACKGROUND: A concern that arises with any change in technique is whether it affects the long-term implant stability. The objective of this study was to evaluate the early migration, measured by radiostereometric analysis (RSA), and the functional outcome of the TriathlonTM cemented knee prosthesis, operated on with or without a tourniquet. During the last decades RSA has emerged as a way to assess prosthetic fixation and long time prognosis. The method has been used extensively in both hip and knee arthroplasty. METHOD: This was a single centre prospective study including 60 patients randomized into two groups operated on either with or without tourniquet. RSA investigation was done within 2-3 days postoperatively after full weight bearing, and then at 3 months, 1 year and 2 years postoperatively. RESULTS: There were no differences between the groups regarding the translation along or rotation around the three coordinal axes, or in maximum total point motion (MTPM). At 2 years the mean MTPM (SD) was 0.71 mm (0.64) for the tourniquet-group and 0.53 mm (0.21) for the non-tourniquet-group. CONCLUSIONS: The tibial tray of the TriathlonTM cemented knee prosthesis showed similar early stability whether operated on with or without tourniquet. LEVEL OF EVIDENCE: Level I. ARTICLE SUMMARY: Article focus: A safety study for total knee replacement operated on with or without perioperative tourniquet regarding the prosthetic fixation. Strengths and limitations: Strength of this study is that it is a randomized prospective trial using an objective measuring tool. The sample size of 25-30 patients is reportedly sufficient for the screening of implants using RSA (1-3). TRIAL REGISTRATION: Clinical trials NCT01604382, Ethics Committee approval D-nr: 144/20085. PMID- 24238651 TI - Gait analysis of fixed bearing and mobile bearing total knee prostheses during walking: do mobile bearings offer functional advantages? AB - BACKGROUND: Limited previous findings have detailed biomechanical advantages following implantation with mobile bearing (MB) prostheses after total knee replacement (TKR) surgery during walking. The aim of this study was to compare three dimensional spatiotemporal, kinematic, and kinetic parameters during walking to examine whether MBs offer functional advantages over fixed bearing (FB) designs. METHODS: Sixteen patients undergoing primary unilateral TKR surgery were randomised to receive either a FB (n=8) or MB (n=8) total knee prosthesis. Eight age and gender matched controls underwent the same protocol on one occasion. A 12 camera Vicon system integrated with four force plates was used. Patients were tested pre-surgery and nine months post-surgery. RESULTS: No significant differences between FB and MB groups were found at any time point in the spatiotemporal parameters. The MB group was found to have a significantly reduced frontal plane knee range of motion (ROM) at pre-surgery than the FB group (FB=14.92+/-4.02 degrees ; MB=8.87+/-4.82 degrees ), with the difference not observed post-surgery. No further significant kinematic or kinetic differences were observed between FB and MB groups. Fixed bearing and MB groups both displayed spatiotemporal, kinematic, and kinetic differences when compared to controls. Fixed bearing and MB groups differed from controls in six and five parameters at nine months post-surgery, respectively. CONCLUSIONS: No functional advantages were found in knees implanted with MB prostheses during walking, with both groups indicative of similar differences when compared to normal knee biomechanics following prosthesis implantation. LEVEL OF EVIDENCE: Level II. PMID- 24238652 TI - Polyethylene particles in joint fluid and osteolysis in revision total knee arthroplasty. AB - BACKGROUND: One of the most frequent reasons for total knee arthroplasty late failure is osteolysis. It has been related to foreign body reaction to polyethylene particles. The aim of this study is to analyse the number, size and morphology of polyethylene particles in synovial fluid in total knee arthroplasty revision and correlate them to the pathology and the degree of osteolysis. METHODS: Synovial fluid was obtained in 12 patients before the revision total knee arthroplasty. Polyethylene particles were isolated and analysed through scanning electron microscopy. Samples of synovial tissue were analysed with optical microscopy while considering the parameters of particles and histiocytic infiltration. Osteolysis was analysed with plain radiography and the macroscopic aspect during surgery. RESULTS: The statistical analysis showed a significant correlation between a high concentration of polyethylene particles in synovial fluid and a high degree of osteolysis. The concentration of particles in synovial fluid also showed a significant correlation with a high degree of particles and histiocytes in the histological analysis. There was a relationship between the size of particles and the degree of osteolysis. No relationship was found between the shape of the particles and the histological findings or the degree of osteolysis. CONCLUSIONS: In an "in vivo" TKA scenario, the presence of a high concentration of polyethylene particles in the synovial fluid seems to be the cause of a highly active foreign body histological reaction, with an increased number of histiocytes, which seems to be the cause of a significant degree of osteolysis around the implant. PMID- 24238655 TI - Toward a modern Mediterranean diet for the 21st century. PMID- 24238656 TI - Epigenetically regulated microRNAs in Alzheimer's disease. AB - Alzheimer's disease (AD) is a complex neurodegenerative disorder involving dysregulation of many biological pathways at multiple levels. Classical epigenetic mechanisms, including DNA methylation and histone modifications, and regulation by microRNAs (miRNAs), are among the major regulatory elements that control these pathways at the molecular level, with epigenetic modifications regulating gene expression transcriptionally and miRNAs suppressing gene expression posttranscriptionally. Epigenetic mechanisms and miRNAs have recently been shown to closely interact with each other, thereby creating reciprocal regulatory circuits, which appear to be disrupted in neuronal and glial cells affected by AD. Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD. PMID- 24238657 TI - Thalamic diffusion differences related to cognitive function in white matter lesions. AB - Cerebral white matter lesions (WMLs) are related to cognitive deficits, probably due to a disruption of frontal-subcortical circuits. We explored thalamic diffusion differences related to white matter lesions (WMLs) and their association with cognitive function in middle-aged individuals. Ninety-six participants from the Barcelona-AsIA Neuropsychology Study were included. Participants were classified into groups based on low grade and high grade of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Tract-Based Spatial Statistics was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) values in significant areas were calculated for each subject and correlated with cognitive performance. Participants with high-grade PVHs and DWMHs showed lower FA thalamic values compared to those with low-grade PVHs and DWMHs, respectively. Decreased FA thalamic values in high-grade DWMHs, but not high-grade PVH, were related to lower levels of performance in psychomotor speed, verbal fluency, and visuospatial skills. Thalamic diffusion differences are related to lower cognitive function only in participants with high-grade DWMHs. These results support the hypothesis that fronto-subcortical disruption is associated with cognitive function only in DWMHs. PMID- 24238658 TI - H5N1, a wealth of knowledge to improve pandemic preparedness. PMID- 24238659 TI - Four-year longitudinal impact evaluation of the Action for Children UK Neglect Project: outcomes for the children, families, Action for Children, and the UK. AB - Neglect has a devastating impact on children and is the most pervasive form of child maltreatment in the United Kingdom. The study purpose was to establish outcomes for neglected children following structured assessment and intervention to ascertain what worked and why it worked. This prospective cohort study included 85 cases of neglected children under 8 years of age from 7 centers across the United Kingdom. Data were collected between 2008 and 2012 through serial quantitative recording of the level of concern about neglect. Serial review of qualitative case-file data was undertaken for detail of assessment, interventions, and evidence of outcomes for the child. Data analysis was undertaken by paired t-test, Chi Square, descriptive statics for categorical data, and, for narrative data, identification of recurring factors and patterns, with correlation of presenting factors, interventions, and outcomes. Paired t test demonstrated significant decrease in overall Action for Children Assessment Tool scores between assessment (M=43.77, SD=11.09) and closing the case (M=35.47, SD=9.6, t(84)=6.77, p<0.01). Improvement in the level of concern about neglect was shown in 79% of cases, with only 21% showing no improvement. In 59% of cases, concern about neglect was removed completely. Use of the assessment tool fostered engagement by parents. The relationship between lack of parental engagement and children being taken into care was statistically significant, with a large effect size (chi(2) 10.66, df1, p=0.0001, OR=17.24). When parents refused or were unable to respond positively to the intervention, children benefited from an expedited move into care. PMID- 24238660 TI - [Microbiological profile of acute viral gastroenteritis attended in a paediatric department of an area with high vaccine cover against rotavirus]. AB - INTRODUCTION: Vaccination against rotavirus has led to a significant decline of the disease. The aim of the present work is to evaluate the clinical and epidemiological features of the viral acute gastroenteritis (AGE) in an area with high immunization coverage against rotavirus. METHOD: A prospective microbiological evaluation was made of stool culture and Real Time Polymerase Chain Reaction (RT-PCR) to gastroenteric virus and genotyping of rotavirus strains in < 5 year-old with AGE episodes attended by or admitted to our hospital from November-March of 2009-2010 and 2010-2011. RESULTS: A total of 51 patients were included, with a mean age (standard deviation) of 19.1 (13.9) months. Stool culture was negative in 23 samples (45% of the samples analyzed), and it was identified a responsible microorganism in 70% by the RT-PCR (16 samples). Rotavirus was the most common isolated microorganism (53%), and G1[P8] the most frequent genotype. A co-infection was detected in 14% of samples (7 patients), and rotavirus and astrovirus were the most frequent etiological agents involved. CONCLUSIONS: Rotavirus, basically G1[P8], is the most common AGE responsible agent identified in our study. The use of RT-PCR enhances the AGE diagnostic sensitivity, and uncovers an important number of viral co-infections. PMID- 24238661 TI - Histological abnormalities induced by the electromyography needle. PMID- 24238662 TI - A structural model of mechanisms predicting depressive symptoms in women following childhood psychological maltreatment. AB - Two underlying mechanisms, emotion dysregulation and negative internalized beliefs, were examined as potential mediators of the association between childhood psychological maltreatment (PM) and depression in emerging adult women. PM was assessed as a multi-faceted construct including aspects of psychological abuse (e.g., corrupting) and psychological neglect (e.g., emotional unresponsiveness) that occurred by parents. Female undergraduates (n=771) completed anonymous, retrospective, self-report surveys assessing childhood PM, current depressive symptoms, emotion dysregulation (lack of emotional clarity and regulation strategies), and negative internalized beliefs (mistrust, shame, and defectiveness). Psychological maltreatment was represented as four subtypes of psychological abuse or neglectful behavior: Emotional Non-Responsiveness, Spurning/Terrorizing, Corrupting, and Demanding/Rigid (i.e., controlling behavior). Both emotion dysregulation and negative internalized beliefs significantly mediated the link between childhood PM and depressive symptoms, accounting for approximately 68% of the variance in symptomatology. Findings suggest the importance of focusing intervention on development of emotion regulation capacity including emotional awareness and regulatory strategies, as well as a focus on core negative beliefs including shame, defectiveness, and mistrust of others. Implications for future research are discussed. PMID- 24238663 TI - "I have quality of life...but...": Exploring support needs important to quality of life in head and neck cancer. AB - PURPOSE OF RESEARCH: Head and neck cancer (HNC) treatment disrupts quality of life and is associated with individualised supportive care needs. This study aimed to describe the support needs that affected the QoL of HNC patients, and to describe how patients coped with unmet support needs. METHODS: Qualitative, semi structured interviews were held with 8 participants previously treated for HNC. Participants were identified through snowball and convenience sampling methods. Interview data was analysed using content analysis (CA). Inductive CA was used to describe support needs and directed CA was guided by the stress appraisal and coping model to describe coping with unmet support needs. RESULTS: Support needs that affected QoL related to acute needs while undergoing treatment and support in coping with permanent treatment side effects. Coping with psychological stressors (i.e. depression and anxiety) affected QoL in the first six to twelve months following treatment. Coping was influenced by loss of access to the supportive hospital environment after treatment, and resulted in feelings of isolation post treatment. CONCLUSIONS: HNC patients drew support from professional and personal networks while undergoing treatment and post treatment. Patients described difficulties in coping with the side effects of treatment and accessing supportive care when away from the hospital setting. The transactional model of stress, appraisal and coping is useful in understanding the psychosocial outcomes of head and neck cancer; however conclusions from this study are limited by a small and homogenous sample. PMID- 24238664 TI - The stressors and vulnerabilities of young single childless women with breast cancer: a qualitative study. AB - PURPOSE OF THE RESEARCH: Marital or partnership status is seldom investigated as a primary contributing factor to women's wellbeing after a diagnosis of breast cancer. It has been suggested, however, that single childless women with breast cancer may face unique stressors. This paper explores the stressors and vulnerabilities of young single childless women with a first episode of breast cancer. METHODS AND SAMPLE: A qualitative descriptive method was used. As part of a larger study examining fertility concerns of young childless women with first episode of breast cancer, in-depth semi-structured interviews were conducted with 10 single women. Recorded interviews were analysed using the framework approach. KEY RESULTS: Findings cover three main themes: partnership worries; fertility concerns; and views about emotional and practical support received. Partnership worries included concerns about having to undergo treatment without a partner to support them; the fear of rejection by potential partners; and feelings about the precious time lost in diagnosis and treatment. Fertility concerns included dilemmas about having children and feelings about the options of pursuing Assisted Reproductive Techniques. Views about the emotional and practical support received included the overall support received as well as perceptions about the attitudes of health professionals towards fertility issues. CONCLUSIONS: Findings indicate that single childless women with breast cancer face additional vulnerabilities and may benefit from tailored support from health care professionals and interventions specifically targeted at them. PMID- 24238665 TI - Genomic analysis of influenza A virus from captive wild boars in Brazil reveals a human-like H1N2 influenza virus. AB - Influenza is a viral disease that affects human and several animal species. In Brazil, H1N1, H3N2 and 2009 pandemic H1N1 A(H1N1)pdm09 influenza A viruses (IAV) circulate in domestic swine herds. Wild boars are also susceptible to IAV infection but in Brazil until this moment there are no reports of IAV infection in wild boars or in captive wild boars populations. Herein the occurrence of IAV in captive wild boars with the presence of lung consolidation lesions during slaughter was investigated. Lung samples were screened by RT-PCR for IAV detection. IAV positive samples were further analyzed by quantitative real-time PCR (qRRT-PCR), virus isolation, genomic sequencing, histopathology and immunohistochemistry (IHC). Eleven out of 60 lungs (18.3%) were positive for IAV by RT-PCR and seven out of the eleven were also positive for A(H1N1)pdm09 by qRRT PCR. Chronic diffuse bronchopneumonia was observed in all samples and IHC analysis was negative for influenza A antigen. Full genes segments of H1N2 IAV were sequenced using Illumina's genome analyzer platform (MiSeq). The genomic analysis revealed that the HA and NA genes clustered with IAVs of the human lineage and the six internal genes were derived from the H1N1pdm09 IAV. This is the first report of a reassortant human-like H1N2 influenza virus infection in captive wild boars in Brazil and indicates the need to monitor IAV evolution in Suidae populations. PMID- 24238666 TI - Age-related and regional differences in the prevalence of hepatitis E virus specific antibodies in pigs in Germany. AB - An increasing number of acute autochthonous human hepatitis E virus (HEV) infections was noticed in Germany and other developed countries, most likely the result of a zoonotic virus transmission from pig, wild boar and deer. Currently there is still a lack of profound data concerning the actual prevalence of HEV specific antibodies in domestic pig herds in Germany, in particular for regions with high pig density, and its age-dependency. 2273 domestic pig sera were collected in 2011 mainly from Bavaria, North Rhine-Westphalia and Lower Saxony from areas having a high pig density. Initially, 420 randomly selected pig sera were tested in three commercially available and in two in-house HEV-antibody ELISAs. 43.6% (183/420) to 65.5% (275/420) of the sera were demonstrated to be reactive against human pathogenic HEV genotypes 1 and/or 3. The majority of sera reacted only weakly or not at all with the rat HEV antigen with very few sera showing a stronger reactivity to this antigen compared to the genotype 3 antigen. The results of all three HEV-IgG tests, i.e. the PrioCHECK((r)) HEV Ab porcine ELISA kit, the ID Screen((r)) Hepatitis E Indirect Multi-species ELISA kit and the genotype 3 in-house ELISA were in good accordance. Therefore, the remaining sera were tested using the PrioCHECK((r)) HEV Ab porcine ELISA kit. Samples with a borderline result were finally determined by application of the conjugate modified recomLine HEV IgG assay. A total of 1065 of the 2273 sera (46.9%) were found to be anti-HEV IgG-positive. While 38.4% (306/796) of fatteners (age between 3 and 9 months) exhibited HEV-specific antibodies, 51.4% (759/1477) of sows (age older than 9 months) exhibited anti-HEV antibodies (P<0.001). Fatteners kept in Southern Germany had a significantly higher HEV IgG prevalence compared to fatteners kept in the high pig density federal states North Rhine-Westphalia and Lower Saxony but also in German federal states with a low pig density. In conclusion, the present study clearly demonstrates that a high percentage of domestic pigs in Germany have had contact with HEV. Seroprevalence depends on the pig's age and herd origin with the most significant regional variations for fatteners. The presence of anti-HEV-free herds may indicate that it is feasible to establish and sustain HEV-free pig herds. HEV seroprevalence still depends on the assay used for testing. This demonstrates an urgent need for test validation. PMID- 24238667 TI - Comparison of multiple genes and 16S-23S rRNA intergenic space region for their capacity in high resolution melt curve analysis to differentiate Mycoplasma gallisepticum vaccine strain ts-11 from field strains. AB - Mycoplasma gallisepticum (MG) is an important avian pathogen causing significant economic losses in the global poultry industry. In an attempt to compare and evaluate existing genotyping methods for differentiation of MG strains/isolates, high resolution melt (HRM) curve analysis was applied to 5 different PCR methods targeting vlhA, pvpA, gapA, mgc2 genes and 16S-23S rRNA intergenic space region (IGSR). To assess the discriminatory power of PCR-HRM of examined genes and IGSR, MG strains ts-11, F, 6/85 and S6, and, initially, 8 field isolates were tested. All MG strains/isolates were differentiated using PCR-HRM curve analysis and genotype confidence percentage (GCP) values of vlhA and pvpA genes, while only 0, 3 and 4 out of 12 MG strains/isolates were differentiated using gapA, mgc2 genes and IGSR, respectively. The HRM curve analysis of vlhA and pvpA genes was found to be highly correlated with the genetic diversity of the targeted genes confirmed by sequence analysis of amplicons generated from MG strains. The potential of the vlhA and pvpA genes was also demonstrated for genotyping of 12 additional MG strains from Europe and the USA. Results from this study provide a direct comparison between genes previously used in sequencing-based genotyping methods for MG strain identification and highlight the usefulness of vlhA and pvpA HRM curve analyses as rapid and reliable tools specially for diagnosis and differentiation of MG strains used here. PMID- 24238668 TI - Characterisation of a type 1 Avian Paramyxovirus belonging to a divergent group. AB - Newcastle disease, induced by a type 1 Avian Paramyxovirus (APMV-1), is one of the most serious poultry diseases. APMV-1 are divided into two classes based on genetic analysis: class II strains have been recovered from wild or domestic birds and include virulent and avirulent isolates whereas class I strains have been mainly isolated from wild birds and are avirulent. Within class I, a new proposed genotype has recently been reported. The only full genome strain of this group is presently characterised from the point of view of codon usage with reference to class I and class II specificities. Class-specific residues were identified on HN and F proteins that are the two major proteins involved in cell attachment and pathogenicity. Comparison of protein patterns and codon usage for this newly identified APMV-1 strain indicates it is similar to class I viruses but contains a few characteristics close to the viruses of class II. Transmission of viruses from this recently identified divergent group from wild birds to domestic birds could have a major impact on the domestic poultry industry. PMID- 24238669 TI - Flagellin and F4 fimbriae have opposite effects on biofilm formation and quorum sensing in F4ac+ enterotoxigenic Escherichia coli. AB - Bacteria that form biofilms are often highly resistant to antibiotics and are capable of evading the host immune system. To evaluate the role of flagellin and F4 fimbriae on biofilm formation by enterotoxigenic Escherichia coli (ETEC), we deleted the fliC (encoding the major flagellin protein) and/or the faeG (encoding the major subunit of F4 fimbriae) genes from ETEC C83902. Biofilm formation was reduced in the fliC mutant but increased in the faeG mutant, as compared with the wild-type strain. The expression of AI-2 quorum sensing associated genes was regulated in the fliC and faeG mutants, consistent with the biofilm formation of these strains. But, deleting fliC and/or faeG also inhibited AI-2 quorum sensing activity. PMID- 24238671 TI - Management of Spigelian hernia caused by necrobiotic fibroma of the uterus in a pregnant woman. AB - INTRODUCTION: Spigelian hernias are a rare type of hernia through the Spigelian aponeurosis. Spigelian hernias are very uncommon and constitute only 0.12% of all abdominal wall hernias. These hernias are located in the aponeurosis of the internal oblique muscle and transverse abdominal muscle. PRESENTATION OF CASE: A 30-year-old woman at 28 weeks' gestation was admitted to the obstetrics department due to pain and swelling in the anterior abdominal right region. On inspection, we suspected either a lipoma, a spontaneous hematoma, a tumor of the abdominal wall, or a Spigelian hernia. A Doppler USG and abdominal and pelvic Magnetic Resonance Imaging revealed necrobiotic fibroma of the uterus in Spigelian hernia. The patient was started on dual analgesic and corticotherapy. Overall, the patient improved one week after the acute episode and had no further pain during her gynecologic follow-up. DISCUSSION: We have reported a first case of Spigelian hernia that was complicated by uterine fibroid. The clinical presentation varies, depending on the contents of the hernial sac and the degree of herniation. MRI is the preferred method for accurately identifying masses of the abdominal wall. Our treatment options were based on the extent of the acute phase reaction and the venous thrombosis. CONCLUSION: It is important to differentiate this rare Spigelian hernia from other hernias as the treatment for this hernia is medical rather than surgical. Before the final choice of treatment is made, digestive surgeons should bear this rare hernia in mind. PMID- 24238670 TI - Over-expression and characterization of NS3 and NS5A of Hepatitis C virus genotype 3a. AB - BACKGROUND: Hepatitis C virus (HCV) is a common and leading cause for liver cirrhosis and hepatocellular carcinoma. Current therapies to treat HCV infection are shown to be partially effective and poorly tolerated. Therefore, ample efforts are underway to rationally design therapies targeting the HCV non structural proteins. Most of the work carried out in this direction has been focusing mainly on HCV genotype 1. Two direct-acting antiviral agents (DAAs) Telaprevir and Boceprevir are being used against genotype 1a infection in combination therapy with interferon and ribavirin. Unfortunately these DAAs are not effective against genotype 3a. Considering the wide spread infection by HCV genotype 3a in developing countries especially South Asia, we have focused on the recombinant production of antiviral drug targets NS3 and NS5A from HCV genotype 3a. These protein targets are to be used for screening of inhibitors. RESULTS: High-level expression of NS3 and NS5A was achieved at 25 degrees C, using ~1 and 0.5 mM Isopropyl beta-D-1-thiogalactopyranoside (IPTG), respectively. Yields of the purified NS3 and NS5A were 4 and 1 mg per liter culture volume, respectively. Although similar amounts of purified NS3 were obtained at 25 and 14 degrees C, specificity constant (Kcat/Km) was somewhat higher at expression temperature of 25 degrees C. Circular dichroism (CD) and Fourier-transform infrared (FT-IR) spectroscopy revealed that both NS3 and NS5A contain a mixture of alpha-helix and beta-sheet secondary structures. For NS3 protein, percentages of secondary structures were similar to the values predicted from homology modeling. CONCLUSIONS: NS3 and NS5A were over-expressed and using Nickel-affinity method both proteins were purified to ~ 95% purity. Yield of the purified NS3 obtained is four fold higher than previous reports. CD spectroscopy revealed that difference in activity of NS3 expressed at various temperatures is not related to changes in global structural features of the protein. Moreover, CD and FT-IR analysis showed that NS3 and NS5A contain both alpha-helical and beta-sheet structures and for NS5A, the proportion is almost equal. The production of NS3 and NS5A in milligram quantities will allow their characterization by biophysical and biochemical means that will help in designing new strategies to fight against HCV infection. PMID- 24238672 TI - The need for burns teaching: a cross-sectional study to assess burns teaching in the United Kingdom. PMID- 24238673 TI - Youth tobacco exposure: the pediatrician's role in addressing a persistent problem. PMID- 24238674 TI - Rights and great responsibilities of academic pediatricians. AB - Abraham Jacobi, in his first address to the newly formed American Pediatric Society over 100 years ago, stated, "Questions of public hygiene and medicine are both professional and social. Thus, every physician is by destiny a citizen of the commonwealth with many rights and great responsibilities." Accordingly, pediatricians have rights and great responsibilities to advocate for children who may be at particularly high risk for adverse outcomes. Often, well-intentioned policies or interventions can have tragic unexpected consequence for these children. In many circumstances, policies are developed by providers, policymakers, and others who may act without sufficient information to understand how a particular policy might adversely affect vulnerable populations. Thus, academic pediatricians should fulfill their great responsibilities by identifying signals from the populations they serve that may indicate unintended consequences of policies, performing the highest quality research and discovery to evaluate these signals, and disseminating the information back to the appropriate decision makers to ensure that policies and interventions result in optimal outcomes for all children. PMID- 24238675 TI - Girl? Interrupted. PMID- 24238676 TI - Cross-cultural training in pediatric residency: every encounter is a cross cultural encounter. PMID- 24238678 TI - Persistence of mental health problems in very young children investigated by US child welfare agencies. AB - OBJECTIVE: To document the persistence and predictors of mental health problems in children aged 12 to 18 months investigated for alleged maltreatment. METHODS: Data came from the second National Survey of Child and Adolescent Well-being (NSCAW II), a longitudinal study of youth 0 to 17.5 years referred to US child welfare agencies. These analyses involved children 12 to 18 months. Baseline sociodemographic, social services, developmental data, and health data were collected on children and caregivers. Potential social-emotional problems at baseline were assessed with the Brief Infant-Toddler Social and Emotional (BITSEA) scales. Outcomes were scores over the clinical cutoff on the Child Behavior Checklist (CBCL) 1.5-5 assessed at 18 months after study entry. RESULTS: The multivariable analyses showed that an elevated BITSEA score at baseline (odds ratio 9.18, 95% confidence interval 1.49, 56.64; P = .018) and living with a depressed caregiver (odds ratio 13.54, 95% confidence interval 2.50, 73.46; P = .003) were associated with CBCL scores in the clinical range at the 18-month follow-up. For children who scored both positive on the BITSEA and lived with a depressed caregiver, 62.5% scored positive on the CBCL compared to 10.7% of the children with one risk factor and 3.8% of the children with neither risk factor. Only 23.9% of children and/or their caregivers received any service. CONCLUSIONS: Data show considerable persistence of mental health problems in very young children that 2 factors could identify. Lack of services to these children is a tremendous missed opportunity for identification and treatment that could potentially prevent more serious mental health problems. PMID- 24238679 TI - The effect of primary care interventions on children's media viewing habits and exposure to violence. AB - OBJECTIVE: To determine if brief primary care interventions can affect children's media viewing habits and exposure to violence. METHODS: English- and Spanish speaking parents of 2- to 12-year-old children presenting to a pediatric primary care clinic participated in a randomized controlled trial. There were 2 intervention groups; one group viewed 5 minutes from the Play Nicely program and another received a handout, "Pulling the Plug on TV Violence." There were 2 control groups; the primary control group received standard primary care, and the alternative control group viewed a program about obesity prevention. The outcome measure was parental report of changes in media viewing habits and changes in exposure to violence. RESULTS: A total of 312 of 443 parents who were randomized completed a 2-week follow-up survey. Compared with the primary control group, parents in the video intervention group were more likely to report a change in their children's media viewing habits (odds ratio [OR] 3.29; 95% confidence interval [CI] 1.66-6.51) and a change in their children's exposure to violence (OR 4.26; 95% CI 1.95-9.27). Compared with the primary control group, parents in the handout group were more likely to report a change in their children's media viewing habits (OR 4.35; 95% CI 2.20-8.60) and a change in their children's exposure to violence (OR 3.35; 95% CI 1.52-7.35). CONCLUSIONS: Brief primary care interventions can affect children's media viewing habits and children's exposure to violence. These results have implications for how to improve primary care services related to decreasing children's media exposure and violence prevention. PMID- 24238677 TI - Strict smoke-free home policies among smoking parents in pediatric settings. AB - OBJECTIVE: To examine strict smoke-free home policies among smoking parents assessed in pediatric offices. METHODS: We analyzed baseline parental survey data from 10 control practices in a national trial of pediatric office-based tobacco control interventions (Clinical Effort Against Secondhand Smoke Exposure, CEASE). We used logistic regression models with generalized estimating equations to examine factors associated with strict smoke-free home policies. RESULTS: Subjects were 952 parents who were current smokers. Just over half (54.3%) reported strict smoke-free home policies. Few reported being asked (19.9%) or advised (17.1%) regarding policies by pediatricians. Factors associated with higher odds of policies were child 5 years or younger (adjusted odds ratio [aOR] 2.43, 95% confidence interval [CI] 1.53, 3.86), nonblack race/ethnicity (aORs 2.17-2.60, 95% CIs 1.25-5.00), non-Medicaid (HMO/private (aOR 1.84, 95% CI 1.31, 2.58); self-pay/other aOR 1.76, 95% CI 1.12, 2.78); well-child versus sick child visit (aOR 1.61, 95% CI 1.11, 2.34), fewer than 10 cigarettes per day (aOR 1.80, 95% CI 1.31, 2.47), no other home smokers (aOR 1.68, 95% CI 1.26, 2.25), only father smoking (aOR 1.73, 95% CI 1.06, 2.83), and strict smoke-free car policy (aOR 3.51, 95% CI 2.19, 5.64). CONCLUSIONS: Nearly half of smoking parents did not have strict smoke-free home policies. Parents were less likely to report policies if they were heavier smokers, black, living with other smokers, or attending a sick child visit; if they did not have a young child or smoke-free car policy; if they had a child on Medicaid; and if anyone other than only the father smoked. Few pediatricians addressed or recommended strict smoke-free home policies in an office visit. The pediatric office encounter represents a currently missed opportunity to intervene regarding smoke-free homes, particularly for high-risk groups. PMID- 24238680 TI - Use of complementary and alternative medical therapies among youth with mental health concerns. AB - BACKGROUND: Use of complementary and alternative medical (CAM) therapies is common among adults with mental health concerns, but little is known about CAM use among adolescents with mental health concerns. METHODS: Data from the 2007 National Health Interview Survey were analyzed for youth from 7 to 17 years old. The study focused on 3 common mental health conditions: attention deficit/hyperactivity disorder (ADHD), anxiety, and depression. CAM therapy use was identified by criteria from the National Institutes of Health National Center for Complementary and Alternative Medicine. RESULTS: In a sample of 5651 individuals, representing 7 million youth, with 1 or more mental health concerns in the past 12 months, 28.9% used 1 or more types of CAM therapy, excluding vitamins/minerals. In contrast, only 11.6% of those without mental health concerns reported CAM therapy use (P < .05). Among youth with 1 or more mental health conditions, the most commonly used CAM therapies were mind-body therapies (16.3%) and biologically based therapies (11%); use was higher for therapies that could be directly accessed (18.6%) than for therapies delivered in groups (11.8%) or through a health professional (10.2%). In the multivariable regression model, demographic factors significantly associated with CAM therapy use were higher household income, higher parental education, having other chronic health conditions, use of prescription medications, and difficulty affording mental health counseling. CONCLUSIONS: Readily accessible CAM therapies are commonly used by youth with ADHD, depression, and anxiety, particularly those who have comorbid chronic health conditions, receive prescription medications, and have difficulty affording counseling. Clinicians can use these data to guide inquiries and counseling. Researchers should explore the longitudinal relationship between access to coordinated care within a medical home and use of CAM therapies among youth with mental health concerns. PMID- 24238681 TI - Using tablet computers to teach evidence-based medicine to pediatrics residents: a prospective study. AB - OBJECTIVE: We sought to determine if tablet computers-supported by a laboratory experience focused upon skill-development-would improve not only evidence-based medicine (EBM) knowledge but also skills and behavior. METHODS: We conducted a prospective cohort study where we provided tablet computers to our pediatric residents and then held a series of laboratory sessions focused on speed and efficiency in performing EBM at the bedside. We evaluated the intervention with pre- and postintervention tests and surveys based on a validated tool available for use on MedEdPORTAL. The attending pediatric hospitalists also completed surveys regarding their observations of the residents' behavior. RESULTS: All 38 pediatric residents completed the preintervention test and the pre- and postintervention surveys. All but one completed the posttest. All 7 attending pediatric hospitalists completed their surveys. The testing, targeted to assess EBM knowledge, revealed a median increase of 16 points out of a possible 60 points (P < .0001). We found substantial increases in individual resident's test scores across all 3 years of residency. Resident responses demonstrated statistically significant improvements in self-reported comfort with 6 out of 6 EBM skills and statistically significant increases in self-reported frequencies for 4 out of 7 EBM behaviors. Attending pediatric hospitalists reported improvements in 5 of 7 resident behaviors. CONCLUSIONS: This novel approach for teaching EBM to pediatric residents improved knowledge, skills, and behavior through the introduction of a tablet computer and laboratory sessions designed to teach the quick and efficient application of EBM at the bedside. PMID- 24238682 TI - Integrating mental health services in primary care continuity clinics: a national CORNET study. AB - OBJECTIVE: To determine whether pediatric continuity clinics integrate mental health (MH) services into care delivery; and to determine whether the level of MH integration is related to access to MH services, types of MH screening performed, self-efficacy, satisfaction with referral sites, and communication with the primary care provider. METHODS: Pediatric Residency Integrated Survey of Mental Health in Primary Care (PRISM_PC) is a newly designed cross-sectional, Web-based survey of continuity clinic directors participating in a national network of pediatric continuity clinics (CORNET). Definitions of MH models included integrated or nonintegrated MH models or traditional care. The survey included questions regarding access, screening that was performed at sites, comfort with MH management as well as provider satisfaction and communication with referral sites. RESULTS: Seventy-eight percent (57 of 73) of CORNET site directors responded, representing input from 30% of US pediatric residency continuity programs. Thirty-five percent (n = 20) reported an integrated MH model while 65% (n = 37) reported a nonintegrated MH model. Seventy-nine percent screened for attention-deficit/hyperactivity disorder, 44% for behavioral-emotional issues, and 19% for pediatric depression. No differences were found in terms of screening or tools used on the basis of the level of MH integration. Those with integrated programs were more likely to have access to an on-site psychologist (P = .001) or psychiatrist (P = .006). CONCLUSIONS: Directors from one-third of training programs surveyed reported some level of MH integration in their primary care teaching clinics. Future studies are needed to compare patient and resident education outcomes between integrated and nonintegrated sites. PMID- 24238683 TI - Innovative online faculty development utilizing the power of social media. AB - OBJECTIVE: Faculty development (FD) is important for continued professional development, but expense and distance remain challenging. These challenges could be minimized by the free and asynchronous nature of social media (SM). We sought to determine the utility and effectiveness of conducting a national online FD activity on Facebook by assessing participants' perceptions and use and facilitators' challenges. METHODS: An educational activity of a national FD program was managed on a closed Facebook group. Activities included postings of educational technology goals, abstracting an article, and commenting on peers' postings. Sources of quantitative data included the Facebook postings and the survey responses. Surveys before, after, and 6 months after the activity assessed knowledge, attitudes and self-reported behaviors. Sources of qualitative data were the open-ended survey questions and the content of the Facebook postings. RESULTS: All participants completed the FD activity and evaluations, yielding 38 postings and 115 comments. Before the activity, 88% had a personal Facebook account, 64% were somewhat/very confident using Facebook, 77% thought SM would be useful for professional networking, and 12% had used it professionally. Six months after the activity, professional usage had increased to 35%. Continued use of Facebook for future presentations of this FD activity was recommended by 76%. Qualitative analysis yielded 12 types of Facebook postings and 7 themes related to using SM for FD. CONCLUSIONS: Conducting a national FD activity on Facebook yielded excellent participation rates and positive participant impressions, and it affected professional usage. Facebook may become an additional tool in the educator's toolbox for FD as a result of its acceptability and accessibility. PMID- 24238684 TI - Teaching and assessment of ethics and professionalism: a survey of pediatric program directors. AB - OBJECTIVE: The Accreditation Council for Graduate Medical Education requires residency programs to provide instruction in and evaluation of competency in ethics and professionalism. We examined current practices and policies in ethics and professionalism in pediatric training programs, utilization of newly available resources on these topics, and recent concerns about professional behavior raised by social media. METHODS: From May to August 2012, members of the Association of Pediatric Program Directors identified as categorical program directors in the APPD database were surveyed regarding ethics and professionalism practices in their programs, including structure of their curricula, methods of trainee assessment, use of nationally available resources, and policies regarding social media. RESULTS: The response rate was 61% (122 of 200). Most pediatric programs continue to teach ethics and professionalism in an unstructured manner. Many pediatric program directors are unaware of available ethics and professionalism resources. Although most programs lack rigorous evaluation of trainee competency in ethics and professionalism, 30% (35 of 116) of program directors stated they had not allowed a trainee to graduate or sit for an examination because of unethical or unprofessional conduct. Most programs do not have formal policies regarding social media use by trainees, and expectations vary widely. CONCLUSIONS: Pediatric training programs are slowly adopting the educational mandates for ethics and professionalism instruction. Resources now exist that can facilitate curriculum development in both traditional content areas such as informed consent and privacy as well as newer content areas such as social media use. PMID- 24238685 TI - Evidence-based milestones for surveillance of cognitive, language, and motor development. AB - OBJECTIVE: Fewer than half of the nation's pediatricians conduct systematic surveillance of young children's development. Because time and cost are among the barriers, our objective was to create a brief set of parent-report questions about cognitive, motor, and language milestones that is freely available and can be administered and scored quickly. METHODS: A team of experts developed candidate items after reviewing existing instruments and prior research. We selected final items based on statistical fit to a graded item response model developed and replicated in separate samples enrolled from primary care settings (n = 469 and 308, respectively). We then developed a 10-item form for each visit on the pediatric periodicity schedule. Combining our initial samples with 395 families enrolled from referral clinics, we tested these forms' concurrent validity with respect to the ASQ-3 and parent reports of developmental diagnoses. RESULTS: A final set of 54 items displayed adequate fit to our statistical model regardless of race/ethnicity, education level, and child gender. Beginning at 4 months, scores on 10-item forms displayed consistent associations with the ASQ-3, and all but the 60-month form detected parents' reports of developmental delay with adequate sensitivity and specificity. CONCLUSIONS: The Milestones is one element of the Survey of Well-being of Young Children (SWYC), a brief but comprehensive screening instrument for children under 5 years. The Milestones is a set of evidence-based items with individual normative data that are appropriate for pediatric surveillance. In addition, the scoring of 10-item Milestones forms may provide many advantages of a first level developmental screening instrument. PMID- 24238686 TI - Three questionnaires to detect psychosocial problems in toddlers: a comparison of the BITSEA, ASQ:SE, and KIPPPI. AB - OBJECTIVE: Validated questionnaires can improve the identification of psychosocial problems in community pediatric services. Our aim was to assess which of 3 short questionnaires-the Brief Infant-Toddler Social and Emotional Assessment (BITSEA), the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE), and the KIPPPI (Brief Instrument Psychological and Pedagogical Problem Inventory)-was most suitable as a routine screening tool for identification among toddlers. METHODS: We included 2106 parents (response rate 81%) of children aged 6, 14, or 24 months at routine well-child visits in 18 services across the Netherlands. Child health care professionals interviewed and examined children and parents. Parents were randomized to complete either the BITSEA or the KIPPPI; all filled out the ASQ:SE and the Child Behavior Checklist. For each questionnaire, we assessed the internal consistency, validity with Child Behavior Checklist-Total Problems Score (CBCL-TPS) as a criterion, and added value to identification compared to clinical assessment alone. RESULTS: Cronbach's alphas of the total scales varied between 0.46 to 0.91. At the ages of 6 and 14 months, none of the instruments studied had adequate validity. At the age of 24 months, only the BITSEA discriminated sufficiently between children with and without problems (sensitivity = 0.84 at specificity = 0.90), but not the other 2 questionnaires (with sensitivity indices varying between 0.53 and 0.60 at similar specificity). The BITSEA at this age offered slightly higher added value to the identification of psychosocial problems by child health care professionals. CONCLUSIONS: For toddlers aged 6 and 14 months, no questionnaire is sufficiently valid to support the identification of psychosocial problems. The BITSEA is the best short tool for the early detection of psychosocial problems in 2-year-old children. PMID- 24238687 TI - Editorial: Advances in SLE--an innovative era for patients and clinicians. PMID- 24238688 TI - Assessment of disease activity, damage and quality of life in systemic lupus erythematosus: new aspects. AB - Systemic lupus erythematosus (SLE) is a multisystem auto-immune disorder that results from a combination of genetic, environmental and hormonal factors. The heterogeneity of disease presentation and course in different individuals and the variability in the disease progression/fluctuations within the same patient have made finding a unifying assessment tool difficult. It is currently accepted that assessment of patients with SLE cannot be accomplished with a single index. Formal evaluation of three aspects of the disease, disease activity, disease damage and patient-related quality of life (QoL), is required. In the recent decade, the pathogenesis of SLE at the cellular and molecular levels has been the subject of much research. Robust assessment tools are needed to correlate the presence of various serological markers with disease activity. In addition, multiple clinical trials of new therapies have necessitated validated measures that can give a sensitive response index. This review focusses on the SLE assessment tools currently in use and their translational application in clinical research and trials. PMID- 24238689 TI - Current management of lupus nephritis. AB - Despite decades of clinical research aimed at finding the most appropriate immunosuppressive regime, lupus nephritis (LN) remains one of the major disease manifestations of systemic lupus erythematosus (SLE) with a great impact on survival and quality of life. We start this review by defining the disease burden, the real-world challenges and the poor prognostic factors. We then discuss the current anti-inflammatory, cytotoxic and biologic therapies, with special emphasis on the need for optimal global care. PMID- 24238690 TI - Adherence to treatment in systemic lupus erythematosus patients. AB - Adherence is defined as "the extent to which a person's behaviour coincides with medical or health advice." Poor adherence to therapeutic regimens is a common and expensive problem in patients with chronic diseases including systemic lupus erythematosus (SLE) and is associated with a higher risk of flares, morbidity, hospitalisations and poor renal outcome. Non-adherence to the treatment is multifactorial for most patients and varies according to unintentional or intentional patterns. The rates of non-adherence in SLE patients range from 3% to 76% depending on the assessment methods, which are all subject to limitations. Indeed, poor adherence to therapeutic regimens is difficult to evaluate. Two studies have shown that undetectable blood hydroxychloroquine (HCQ) concentration may be a simple, objective and reliable marker of non-adherence in SLE patients. The accurate diagnosis of non-adherence may prevent one from incorrectly interpreting disease manifestations as a lack of response. It may then avoid an unnecessary or even dangerous treatment escalation. PMID- 24238691 TI - Biologics in SLE: towards new approaches. AB - In recent years the use of biologic therapies in the management of systemic lupus erythematosus (SLE) has increased, and a number of clinical trials have highlighted both the potential and the pitfalls in the development of such agents. Many investigators reported that the off-label use of rituximab seemed promising in patients with refractory disease, but randomised trials with this agent failed. Likewise, the theoretical appeal of the co-stimulation blocker abatacept could not be confirmed in two clinical trials. Various considerations and post hoc analyses nonetheless suggest that these two biologics might have a role in the treatment of SLE. The anti-B-lymphocyte stimulator (anti-Blys) antibody belimumab demonstrated efficacy and safety in two large randomised trials and became the first approved biologic for lupus. Use in clinical practice has increased slowly, in part, due to uncertainty over which patients should be treated with this agent and in what stage of the disease. Finally, several other biologic agents are currently in advanced stages of clinical development for SLE. The overall picture that emerges is one of optimism that advances in SLE therapy will be realised through the targeted use of an increasing number of biologics. PMID- 24238692 TI - Paediatric-onset systemic lupus erythematosus. AB - Paediatric-onset systemic lupus erythematosus (SLE) is usually more severe than its adult counterpart. In particular, there is a higher incidence of renal and central nervous system involvement. Specific measures to assess disease activity and damage have been implemented. The disease is very rare before the fifth birthday and therefore the onset of an SLE picture in the first years of life should lead to the suspicion of the presence of one of the rare monogenic diseases that causes SLE or of one of those congenital diseases that has been showed to be closely associated with the SLE. PMID- 24238693 TI - Fatigue, health-related quality of life and other patient-reported outcomes in systemic lupus erythematosus. AB - OBJECTIVE: This chapter aims to evaluate current knowledge of the burden of systemic lupus erythematosus (SLE) on individual patients, with a particular focus on health-related quality of life (HRQoL), activities of daily living (ADLs), individual symptoms, such as fatigue and pain, work disability and employment. METHODOLOGY: A literature search was performed in Medline (PubMed) and a qualitative analysis was done of all publications relating to the burden of SLE (January 2000 to May 2010, updated in June 2013) matching the following inclusion criteria: prospective studies involving >=100 patients with SLE; studies focussing on QoL, ADL, function/disability, patient perceptions/experience of their illness, physical/psychological/social impact, unmet needs, work disability/employment status or specific signs/symptoms expected to impact on HRQoL/ADL; studies predominantly involving patients of Caucasian ethnicity; and studies based in Europe, North America or Australia. Studies in juvenile patients; studies of the impact of obesity; studies of non pharmacological interventions, dietary supplements or alternative medicines; and health-economic analyses were excluded. RESULTS/CONCLUSIONS: The present literature analysis showed that SLE has a considerable impact on the HRQoL of patients and their ability to carry out normal daily activities, resulting in a high prevalence of disability. The HRQoL of patients with SLE is consistently lower than that of matched healthy control subjects or patients with other chronic diseases. Predictors of poor HRQoL in patients with SLE include older age, fatigue and the presence of co-morbid neurological or psychiatric disorders, particularly depression or anxiety. Conversely, clinical measures of disease activity and organ damage are poor indicators of patients' HRQoL. Even though current evidence gives an insight into the HRQoL in patients with SLE, there are still many areas where results need to be confirmed or clarified and therefore there is the need to conduct further studies including trials with HRQoL as a primary objective. PMID- 24238694 TI - Management of infection in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal autoantibody production and clearance. This immunological background has been suggested to play a role in the susceptibility of SLE patients to infection. Moreover, drugs (most of them immunosuppressive or immunomodulating agents) used in the treatment of moderate and severe lupus give rise to a tendency for infections, including opportunistic ones. Infections may mimic the exacerbations of SLE, leading to confusion over the diagnosis and appropriate treatment. Despite increased awareness of this problem, infections remain a major source of morbidity and mortality in SLE. There are various strategies which can be applied to try and reduce the risk of infection in SLE patients. Options include vaccinations, antibiotic/antiviral prophylaxis and intravenous immunoglobulins. PMID- 24238696 TI - Demyelinating disease in SLE: is it multiple sclerosis or lupus? AB - Among the 12 systemic lupus erythematosus (SLE)-related central nervous system (CNS) syndromes defined by the American College of Rheumatology (ACR), demyelinating syndrome and myelopathy are two of the less prevalent and more poorly understood ones. One important issue concerning demyelinating disease in SLE is that it can be easily misdiagnosed with other central nervous system demyelinating disorders such as multiple sclerosis (MS). A clinically isolated neurological syndrome can be the presenting feature before other concomitant symptoms of SLE appear or definite MS is diagnosed. Although challenging, some diagnostic tests used in clinical practice and research may help to differentiate between these entities. These tests have improved the understanding of the pathogenesis in these diseases, but some points, such as the role of antiphospholipid antibodies in SLE-associated transverse myelitis, remain unclear and are a matter of ongoing debate. This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica. PMID- 24238695 TI - Cutaneous lupus erythematosus: diagnosis and treatment. AB - Cutaneous lupus erythematosus (CLE) encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several sub-types, including acute CLE (ACLE), sub-acute CLE (SCLE) and chronic CLE (CCLE). CCLE includes discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain cutaneous lupus and lupus tumidus. The diagnosis of these diseases requires proper classification of the sub-type, through a combination of physical examination, laboratory studies, histology, antibody serology and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. The treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring or treatment-refractory disease. In this chapter, we discuss issues in classification and diagnosis of the various sub-types of CLE, as well as provide an update on therapeutic management. PMID- 24238697 TI - Pulmonary hypertension in systemic lupus erythematosus. AB - Systemic lupus erythematosus is associated with several forms of pulmonary hypertension. It can cause pulmonary hypertension through pulmonary thromboembolic disease, left heart disease and lung disease as well as causing an isolated pulmonary vasculopathy called pulmonary arterial hypertension. The true prevalence of pulmonary arterial hypertension in patients with lupus is not known but probably is no more than 1%. Currently, treatment for lupus-associated pulmonary arterial hypertension is with pulmonary vasodilators including phosphodiesterase-5 inhibitors, endothelin receptor antagonists and prostacyclin analogues, as it is for other causes of pulmonary arterial hypertension. Case series suggest there may be a special role for immunosuppression in this rare group of patients. We present two brief case histories and summarise our experience over 15 years. Prognosis is better in lupus-associated pulmonary arterial hypertension than in systemic sclerosis-associated pulmonary arterial hypertension, but unfortunately it remains a fatal condition in most patients. PMID- 24238699 TI - The effectiveness of therapeutic exercise for joint hypermobility syndrome: a systematic review. AB - BACKGROUND: Joint hypermobility syndrome (JHS) is a heritable connective tissue disorder characterised by excessive range of movement at multiple joints accompanied by pain. Exercise is the mainstay of management yet its effectiveness is unclear. OBJECTIVES: To establish the effectiveness of therapeutic exercise for JHS. DESIGN: Systematic literature review. DATA SOURCES: A search of nine online databases, supplemented by a hand search and snowballing. STUDY ELIGIBILITY CRITERIA (PARTICIPANTS AND INTERVENTIONS): People diagnosed with JHS (rather than asymptomatic generalised joint laxity); therapeutic exercise (of any type) used as an intervention; primary data reported; English language; published research. STUDY APPRAISAL AND SYNTHESIS METHODS: Methodological quality was appraised by each reviewer using Critical Appraisal Skills Programme checklists. Articles were then discussed collectively and disagreements resolved through debate. RESULTS: 2001 titles were identified. Four articles met the inclusion criteria, comprising one controlled trial, one comparative trial and two cohort studies. All studies found clinical improvements over time. However there was no convincing evidence that exercise was better than control or that joint-specific and generalised exercise differed in effectiveness. LIMITATIONS: The studies used heterogeneous outcome measures, preventing pooling of results. Only one study was a true controlled trial which failed to report between-group statistical analyses post-treatment. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There is some evidence that people with JHS improve with exercise but there is no convincing evidence for specific types of exercise or that exercise is better than control. Further high quality research is required to establish the effectiveness of exercise for JHS. PMID- 24238698 TI - Managing lupus patients during pregnancy. AB - Systemic lupus erythematosus (SLE) is an auto-immune disease, primarily affecting young females. Pregnancy in a woman with SLE remains a high-risk situation with higher maternal and foetal mortality and morbidity. Although live births are achieved in majority of the pregnancies, active disease and major organ involvement can negatively affect the outcomes. A higher risk of foetal loss, pre term birth, intra-uterine growth restriction (IUGR) and neonatal lupus syndromes (NLSs) are major foetal issues. Mothers are faced with disease flares, pre eclampsia and other complications. Disease flares during SLE pregnancy pose the unique issue of recognition and differentiation between physiologic changes and disease state. Similarly, pre-eclampsia and lupus nephritis may lead to diagnostic confusion. Treatment choices during pregnancy are limited to a few safe drugs, further restricting the options. Refractory pregnancy loss associated with anti-phospholipid antibodies (aPLs) and complete heart block associated with anti-Ro antibodies remain unresolved issues. A multidisciplinary approach, with close monitoring, is essential for optimal outcomes. PMID- 24238700 TI - Patients with rotator cuff tendinopathy can successfully self-manage, but with certain caveats: a qualitative study. AB - OBJECTIVES: Evidence has emerged supporting the value of loaded exercises for rotator cuff tendinopathy but there are barriers that might prevent implementation of this intervention in the real-world. The purpose of this study was to explore these potential barriers with participants involved in a pilot randomised controlled trial (RCT) investigating a self-managed loaded exercise intervention. DESIGN: A qualitative study within the framework of a mixed methods design. Data were collected using individual interviews and analysed using the framework method. SETTING: One private physiotherapy clinic in northern England. PARTICIPANTS: Six patients and two physiotherapists were purposively sampled from those allocated to the self-managed exercise group within the RCT. RESULTS: Three themes were generated: (1) Expectations and preferences, (2) characteristics of an unsuccessful outcome, (3) characteristics of a successful outcome. Most patients expressed expectations contrary to the philosophy of a self-managed approach. But this did not serve as a barrier when the intervention was offered within a positive and supporting environment where patients understood the reasons for undertaking the exercise, effectively self-monitored and engaged with pro-active follow-up. An early and appreciable response to therapy was also a key factor influencing continuing engagement with the exercise programme. CONCLUSION: With certain caveats including the need to recognise and respond to individual characteristics, implement effective knowledge translation strategies and the need to engage with appropriately timed pro-active follow-up, the potential to implement programmes of self-managed loaded exercise for patients with rotator cuff tendinopathy in the real-world and in further research studies appears feasible but challenging. PMID- 24238701 TI - Magnetoreception: an unavoidable step for plant evolution? AB - The geomagnetic field (GMF) is steadily acting on living systems, and influences many biological processes. In animals, the mechanistic origin of the GMF effect has been clarified and cryptochrome has been suggested as a chemical magnetoreceptor. Here we propose a possible role for the GMF variations in plant evolution. PMID- 24238702 TI - Two for all: receptor-associated kinases SOBIR1 and BAK1. AB - Leucine-rich repeat-receptor-like proteins (LRR-RLPs) are ubiquitous cell surface receptors lacking a cytoplasmic signalling domain. For most of these LRR-RLPs, it remained enigmatic how they activate cellular responses upon ligand perception. Recently, the LRR-receptor-like kinase (LRR-RLK) SUPPRESSOR OF BIR1-1 (SOBIR1) was shown to be essential for triggering defence responses by certain LRR-RLPs that act as immune receptors. In addition to SOBIR1, the regulatory LRR-RLK BRI1 ASSOCIATED KINASE-1 (BAK1) is also required for LRR-RLP function. Here, we compare the roles of SOBIR1 and BAK1 as regulatory LRR-RLKs in immunity and development. BAK1 has a general regulatory role in plasma membrane-associated receptor complexes comprising LRR-RLPs and/or LRR-RLKs. By contrast, SOBIR1 appears to be specifically required for the function of receptor complexes containing LRR-RLPs. PMID- 24238703 TI - Long-term average spectra of adult Iranian speakers' voice. AB - INTRODUCTION: Long-term average spectrum (LTAS) allows quantifying the voice quality and provides an overview of the mean spectral characteristics of a voice. The aims of this study were to survey normal spectral characteristics of Persian and investigate sex-related changes in the source characteristics of dynamic speech using LTAS. METHOD: Speech samples obtained from 30 male and 30 female Persian-speaking participants reading a text in habitual pitch and loudness level. At the LTAS window and using Praat software, the amplitude values were obtained at equal intervals of 160 Hz, ranging from 0 to 8 kHz. RESULTS: The main features of the average spectrum were as follows: peak in the region of 480 Hz with a reduction at higher frequencies, a 20 dB decline from 480 to 960 Hz, a flat region from 960 to 1920 Hz, a further decline from 1920 to 3040 Hz, and a further flat region from 3040 to 8000 Hz. In comparison to men, women revealed significant lower levels of amplitude at frequencies of 160 and 320 Hz and higher levels of amplitude at frequencies of 960, 3360, 3520, 3680, 3840, and 5920 Hz. CONCLUSION: The overall shape and gender-related energy distribution pattern of the LTAS of Persian were more similar to those of English than to those of Korean. The more phonetic differences between Persian and Korean compared with Persian and English might contribute to different spectral characteristics. The present study tried to clarify the spectral characteristics of Iranian male and female voices and focused on more breathy voice quality for women than men. PMID- 24238704 TI - Size and mass determination of silver nanoparticles in an aqueous matrix using asymmetric flow field flow fractionation coupled to inductively coupled plasma mass spectrometer and ultraviolet-visible detectors. AB - The powerful antibacterial properties of engineered silver nanoparticles (AgNPs) have, in recent years, led to a great increase in their use in consumer products such as textiles and personal care products offers. This widespread and often indiscriminate use of nano-silver is inevitably increasing the probability that such materials be accidentally or deliberately lost into the environment. Once present in the environment the normally useful antibacterial properties of the silver may instead become a potential hazard to both man and the environment. In the face of such concerns it therefore desirable to develop easy, reliable and sensitive analytical methods for the determination of nano-sized silver in various matrices. This paper describes a method for the simultaneous determination of particles-size and mass-concentration of citrate-stabilized silver nano-particles in aqueous matrices by asymmetric flow field flow fractionation coupled to an ICP-mass spectrometer and UV/vis detector. In particular, this work has evaluated the use of pre-channel injections of mono dispersed silver nano-particles as a means of accurate size and mass-calibration. The suitability of the method as a means to generate accurate and reliable results was verified by determination of parameters such as precision under repeatability conditions, linearity, accuracy, recovery and analytical sensitivity. PMID- 24238705 TI - Recovery of Peniophora cinerea laccase using aqueous two-phase systems composed by ethylene oxide/propylene oxide copolymer and potassium phosphate salts. AB - Aqueous two-phase systems (ATPSs) composed by UCON (ethylene oxide/propylene oxide copolymer) and potassium phosphate salts were for the first time evaluated in the recovery of Peniophora cinerea laccase from complex fermented medium. The ATPSs were obtained by combining the random copolymer UCON with KH2PO4, potassium phosphate buffer pH 7 or K2HPO4. According to the results, protein partition occurred predominantly toward the saline phase (bottom phase) of the ATPSs, while some contaminants such as pigments partitioned mainly to the top phase. In preliminary tests, it was found that the salt with the lowest pH value (KH2PO4, pH 4.6) stimulated the enzyme activity, while the other salts (pH between 7.0 and 9.5) caused a strong inhibition. However, the salt inhibition was not observed in the equilibrium phases of the UCON-Potassium phosphate ATPSs. The laccase recovery was high for all the biphasic systems, but the highest value (134%) was obtained when using UCON combined with KH2PO4. When compared to conventional concentration and purification methods (lyophilization, ammonium sulfate precipitation, ultrafiltration, and ion exchange chromatography), ATPS was demonstrated to be an efficient alternative for P. cinerea laccase recovery from fermented medium. PMID- 24238706 TI - A new N-hydroxyethyliminodiacetic acid modified core-shell silica phase for chelation ion chromatography of alkaline earth, transition and rare earth elements. AB - Bare core-shell silica (1.7MUm) has been modified with iminodiacetic acid functional groups via standard silane chemistry, forming a new N hydroxyethyliminodiacetic acid (HEIDA) functionalised core-shell stationary phase. The column was applied in high-performance chelation ion chromatography and evaluated for the retention of alkaline earth, transition and heavy metal cations. The influence of nitric acid eluent concentration, addition of complexing agent dipicolinic acid, eluent pH and column temperature on the column performance was investigated. The efficiencies obtained for transition and heavy metal cations (and resultant separations) were comparable or better than those previously obtained for alternative fully porous silica based chelation stationary phases, and a similarly modified monolithic silica column, ranging from ~15 to 56MUm HETP. Increasing the ionic strength of the eluent with the addition of KNO3 (0.75M) and increasing the column temperature (70 degrees C) facilitated the isocratic separation of a mixture of 14 lanthanides and yttrium in under 12min, with HETP averaging 18MUm (7MUm for Ce(III)). PMID- 24238707 TI - Development and validation of an extraction method for the determination of pro inflammatory eicosanoids in human plasma using liquid chromatography-tandem mass spectrometry. AB - A simple method coupled to liquid chromatography-tandem mass spectrometry (LC MS/MS) was developed and validated for the extraction of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) from human plasma. The extraction protocol consisted of adding formic acid (10 MUL) and acetonitrile (140 MUL) to human plasma (50 MUL) and further injection of the supernatant (25 MUL) into the LC-MS/MS. The method was selective for PGE2 and LTB4 and the regression models, based on deuterated internal standards (30 ng mL(-1) PGE2-d4 and 40 ng mL(-1) LTB4-d4), were linear over the concentration range 1.0-50.0 ng mL(-1) with limits of detection (3 * sigmablank) and quantification (6 * sigmablank) of 0.5 ng mL(-1) and 1 ng mL(-1) for both eicosanoids. The recovery ranges were 95.1-104.7% for PGE2 and 86.4 103.2% for LTB4. The developed method was successfully implemented on plasma samples from patients before and after exposure to certain anti-inflammatory treatment. PMID- 24238708 TI - Dithienyl benzothiadiazole derivatives: a new type of stationary phases for capillary gas chromatography. AB - Dithienyl benzothiadiazole (TBT) derivatives are characteristic of specific molecular structures and excellent thermal stability, offering the great potential for their use as stationary phases for capillary gas chromatography (GC). However, no related publications are available to date. Here we first report the exploration of two TBT derivatives, namely, 4,7-bis(5-dodecylthiophen 2-yl) benzothiadiazole (TBT-C12, a new derivative), and 4,7-di(thiophen-2-yl) benzothiadiazole (TBT), for the purpose. First, TBT-C12 and TBT were synthesized and statically coated onto capillary columns. Both of the as-prepared columns were characterized as nonpolar nature by the determined McReynolds constants. The results showed that both TBT-C12 and TBT columns achieved excellent separations for n-alkanes, esters and polycyclic aromatic hydrocarbons (PAHs), and the TBT C12 column exhibited better thermal stability (up to 280 degrees C) than the TBT column. Moreover, a comparative study between the TBT-type columns and a commercial column was also made, suggesting the better selectivity of the TBT type stationary phases toward n-alkanes and PAHs than that of the commercial one. Additionally, thermodynamic parameters suggested that the retention behaviors of n-alkanes and PAHs on the TBT-C12 column was mainly controlled by entropy change (DeltaS). In conclusion, this work demonstrates the excellent chromatographic performance of TBT derivatives as a new type of GC stationary phases and their potential in separation science. PMID- 24238709 TI - High-resolution magic angle spinning description of the interaction states and their kinetics among basic solutes and functionalized silica materials. AB - Modeling of the interaction is crucial to understanding and predicting chromatography. However, the complexity and variety of the grafted motifs render the creation of an accurate model overwhelmingly challenging, so that most often the classification of column separation properties is described by monitoring the retention times of carefully selected control molecules. We analyzed here the characteristics of the interplay of compounds of basic nature by (1)H HRMAS NMR, which provide relevant descriptors for products with pharmaceutical properties, with chromatographic phases for Reversed Phase Liquid Chromatography. Eight grafted silica phases were selected, differing to enhance specific structural properties (monomeric and polymeric grafts, endcapping or not, carbon content, alkyl with polar embedded group or alkyl bonded chain, chemical nature of end capping, native silica). These materials were put in interaction with five basic molecules, previously chosen as probes for the evaluation of efficient base deactivated liquid stationary phases using five theoretical molecular descriptors to cover a large scale of molecular volume, polar surface area, LogP, hydrogen bond donor capacity and finally hydrogen-bond acceptor capacity. (1)H HRMAS NMR was capable of describing qualitatively a wealth of interaction states, characterized both thermodynamically and kinetically. In one case (penbutolol) up to five interaction states could be differentiated. Variable temperature experiments revealed the complexity of the retention process on grafted silica as in some cases the kinetics of the interaction is shown to slow down on increasing the temperature. PMID- 24238710 TI - Recent developments and future trends in solid phase microextraction techniques towards green analytical chemistry. AB - Solid phase microextraction find increasing applications in the sample preparation step before chromatographic determination of analytes in samples with a complex composition. These techniques allow for integrating several operations, such as sample collection, extraction, analyte enrichment above the detection limit of a given measuring instrument and the isolation of analytes from sample matrix. In this work the information about novel methodological and instrumental solutions in relation to different variants of solid phase extraction techniques, solid-phase microextraction (SPME), stir bar sorptive extraction (SBSE) and magnetic solid phase extraction (MSPE) is presented, including practical applications of these techniques and a critical discussion about their advantages and disadvantages. The proposed solutions fulfill the requirements resulting from the concept of sustainable development, and specifically from the implementation of green chemistry principles in analytical laboratories. Therefore, particular attention was paid to the description of possible uses of novel, selective stationary phases in extraction techniques, inter alia, polymeric ionic liquids, carbon nanotubes, and silica- and carbon-based sorbents. The methodological solutions, together with properly matched sampling devices for collecting analytes from samples with varying matrix composition, enable us to reduce the number of errors during the sample preparation prior to chromatographic analysis as well as to limit the negative impact of this analytical step on the natural environment and the health of laboratory employees. PMID- 24238711 TI - A novel stop-flow two-dimensional liquid chromatography-mass spectrometry method for lipid analysis. AB - A novel on-line two dimensional liquid chromatography (2D LC) based on stop-flow mode coupled with electrospray ionization mass spectrometry (ESI-MS) method was established to separate lipids in human plasma. Hydrophilic interaction liquid chromatography (HILIC) in the first dimension and reversed-phase liquid chromatography (RP LC) in the second dimension were used to separate the lipids into six fractions based on their polar head groups and further into peaks based on aliphatic chains, respectively. A new stop-flow interface with a trap column and an extra make-up flow was designed to construct this system and trap the components eluted from the first dimension. Moreover, the same length of analytical columns and similar flow rates were used in the first and second dimensions. Therefore, the new stop-flow 2D LC system can avoid the sensitivity decrease caused by the dilution effect, which is the shortcoming of comprehensive 2D LC. Three hundred and seventy-two lipids were identified from plasma extract using this 2D LC coupled with ESI-MS in positive mode, and 88 more lipids were detected than one-dimensional RP LC analysis. Peak capacity of this stop-flow 2D LC was 415, which is similar to that of comprehensive 2D LC. The linearity, repeatability and sensitivity of this method were satisfactory, which demonstrated that this method was also suitable for quantitative analysis. All these results indicated that this on-line 2D LC method is powerful for qualitative and quantitative analysis of complex lipids. PMID- 24238712 TI - Ion-pair ultra-high performance liquid chromatographic analysis of monoamines: peak-splitting at high flow rates. AB - The use of ion-pair ultra-high performance liquid chromatography (UHPLC) coupled with electrochemical detection (ECD) is of great interest for the fast and sensitive determination of the monoamine neurotransmitters dopamine, noradrenaline and serotonin in microdialysis samples. However, when applying high flow rates in ion-pair UHPLC, other peaks than the initial compound peaks appear on the chromatogram. This peak-splitting phenomenon is caused by disturbed ion pair retention mechanisms. The influence of several chromatographic parameters is investigated. Peak-splitting is delayed to higher flow rates when increasing the concentration of ion-pair reagent or buffering agent in the mobile phase, when decreasing the percentage of organic modifier in the mobile phase, when applying a stationary phase with a smaller amount of packing material or when increasing the separation temperature. One or a combination of these conditions can be applied to analyze the monoamine neurotransmitters using ion-pair UHPLC-ECD at high flow rates. PMID- 24238713 TI - Synthesis of 3-fluorobenzoyl chloride functionalized magnetic sorbent for highly efficient enrichment of perfluorinated compounds from river water samples. AB - A novel type of magnetic nanoparticles, 3-fluorobenzoyl chloride functionalized magnetic nanoparticles (Fe3O4@SiO2@FBC MNPs) was successfully synthesized. It was applied to the extraction and determination of perfluorinated compounds (PFCs) by coupling with ultra-high performance liquid chromatography with tandem triple quadrupole mass spectrometry (UHPLC-MS/MS). Due to the fluorous-fluorous interaction, the magnetic nanoparticles displayed excellent extraction performance for 6 PFCs, including perfluoroheptanoic acid (PFHpA), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoA), perfluorotetradecanoic acid (PFTeDA), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). The UHPLC separation of PFCs was very quick and could be achieved within 6min. Various factors that may influence the magnetic solid-phase extraction (MSPE) efficiency, such as sorbent amount, desorption solvent, extraction time, pH value of water samples and sample volume, were investigated in detail. Under the optimum conditions, the linear ranges of six PFCs were 0.25-25ng/L with the limits of detection (S/N=3) ranging from 0.01 to 0.06ng/L. Finally, the method was successfully applied to different river water samples, and the recoveries were in the range of 89.34-111.32%. These results indicated that the prepared Fe3O4@SiO2@FBC sorbents could efficiently enrich PFCs and that the proposed method is reliable. PMID- 24238714 TI - Leaving buprenorphine treatment: patients' reasons for cessation of care. AB - Many opioid-dependent patients leave treatment prematurely. This study is a planned secondary analysis from a randomized trial of counseling for African Americans (N=297) entering buprenorphine treatment at one of two outpatient programs. This study examines: (1) whether patients' initial treatment duration intentions prospectively predict retention; and (2) patients' reasons for leaving treatment. Participants were queried about their treatment duration intentions at treatment entry, and their reasons for leaving treatment at 6-month follow-up. At baseline, 28.0% reported wanting to stay in buprenorphine treatment less than 6 months, while 42.1% actually left buprenorphine treatment within 6 months. However, participants intending short-term buprenorphine at the outset were not at elevated risk of early treatment discontinuation (OR=1.15; p=.65). Participants attributed treatment cessation predominantly to conflicts with staff, involuntary discharge, and perceived inflexibility of the program. Future research should examine patient-centered models of buprenorphine treatment that could improve retention. PMID- 24238716 TI - Predictors of substance abuse treatment participation among homeless adults. AB - The current study focuses on the relationships among a trauma history, a substance use history, chronic homelessness, and the mediating role of recent emotional distress in predicting drug treatment participation among adult homeless people. We explored the predictors of participation in substance abuse treatment because enrolling and retaining clients in substance abuse treatment programs is always a challenge particularly among homeless people. Participants were 853 homeless adults from Los Angeles, California. Using structural equation models, findings indicated that trauma history, substance use history and chronicity of homelessness were associated, and were significant predictors of greater recent emotional distress. The most notable result was that recent emotional distress predicted less participation in current substance abuse treatment (both formal and self-help) whereas a substance use history alone predicted significantly more participation in treatment. Implications concerning treatment engagement and difficulties in obtaining appropriate dual-diagnosis services for homeless mentally distressed individuals are discussed. PMID- 24238715 TI - Recovery among adolescents: models for post-treatment gains in drug abuse treatments. AB - Recovery among adolescents undergoing substance abuse treatment was modeled in terms of pre-treatment motivation, therapeutic relationships, psychological functioning, treatment retention, legal pressures, DSM diagnoses, and client demographics. To address between program differences, a within-covariance matrix, based on 547 youth, was used. Applicability of the results across treatment modalities was also examined. The data were from the NIDA-sponsored DATOS Adolescent study. Results from structural equation models (estimated using Mplus) indicated that higher pre-treatment motivation predicted stronger counselor and in-treatment peer relationships, better counselor relationships and retention predicted less illegal drug use at follow-up, and DSM diagnosis was important in the treatment process. Overall, illegal drug use at follow-up was associated with post-treatment alcohol consumption, cigarette use, condom nonuse, psychological distress, criminality, and school non-attendance. The results document the importance of motivation and therapeutic relationships on recovery, even when taking into account the relative effects of legal pressures, DSM diagnoses, and demographics. PMID- 24238717 TI - Criminal justice outcomes after engagement in outpatient substance abuse treatment. AB - The relationship between engagement in outpatient treatment facilities in the public sector and subsequent arrest is examined for clients in Connecticut, New York, Oklahoma and Washington. Engagement is defined as receiving another treatment service within 14 days of beginning a new episode of specialty treatment and at least two additional services within the next 30 days. Data are from 2008 and survival analysis modeling is used. Survival analyses express the effects of model covariates in terms of "hazard ratios," which reflect a change in the likelihood of outcome because of the covariate. Engaged clients had a significantly lower hazard of any arrest than non-engaged in all four states. In NY and OK, engaged clients also had a lower hazard of arrest for substance related crimes. In CT, NY, and OK engaged clients had a lower hazard of arrest for violent crime. Clients in facilities with higher engagement rates had a lower hazard of any arrest in NY and OK. Engaging clients in outpatient treatment is a promising approach to decrease their subsequent criminal justice involvement. PMID- 24238718 TI - The long-term effect of zinc soil contamination on selected free amino acids playing an important role in plant adaptation to stress and senescence. AB - Increased endogenous plant cytokinin (CK) content through transformation with an isopentyl transferase (ipt) gene has been associated with improved plant stress tolerance. The objective of this study is to determine amino acid changes associated with elevated CK production in ipt transgenic tobacco (Nicotiana tabacum L., cv. Wisconsin 38). Nontransformed (WT) and transformed tobacco plants with ipt gene controlled by senescence-activated promoter (SAG) were exposed to zinc soil contamination (tested levels Zn1=250, Zn2=500, Zn3=750 mg kg(-1) soil). The Zn effect on plant stress metabolism resulted in changes in levels of selected free amino acids playing an important role in adaptation to stress and plant senescence (alanine, leucine, proline, methionine and gamma-aminobutyrate) and differed for transformed and nontransformed tobacco plants. Analyses of amino acids confirmed that SAG tobacco plants had improved zinc tolerance compared with the WT plants. The enhanced Zn tolerance of SAG plants was associated with the maintenance of accumulation of proline, methionine and gamma-aminobutyrate. The concentrations of leucine and alanine did not show significant differences between plant lines. PMID- 24238719 TI - Effects of the neonicotinoid pesticide thiamethoxam at field-realistic levels on microcolonies of Bombus terrestris worker bumble bees. AB - Neonicotinoid pesticides are currently implicated in the decline of wild bee populations. Bumble bees, Bombus spp., are important wild pollinators that are detrimentally affected by ingestion of neonicotinoid residues. To date, imidacloprid has been the major focus of study into the effects of neonicotinoids on bumble bee health, but wild populations are increasingly exposed to alternative neonicotinoids such as thiamethoxam. To investigate whether environmentally realistic levels of thiamethoxam affect bumble bee performance over a realistic exposure period, we exposed queenless microcolonies of Bombus terrestris L. workers to a wide range of dosages up to 98 MUgkg(-1) in dietary syrup for 17 days. Results showed that bumble bee workers survived fewer days when presented with syrup dosed at 98 MUg thiamethoxamkg(-1), while production of brood (eggs and larvae) and consumption of syrup and pollen in microcolonies were significantly reduced by thiamethoxam only at the two highest concentrations (39, 98 MUgkg(-1)). In contrast, we found no detectable effect of thiamethoxam at levels typically found in the nectars of treated crops (between 1 and 11 MUgkg( 1)). By comparison with published data, we demonstrate that during an exposure to field-realistic concentrations lasting approximately two weeks, brood production in worker bumble bees is more sensitive to imidacloprid than thiamethoxam. We speculate that differential sensitivity arises because imidacloprid produces a stronger repression of feeding in bumble bees than thiamethoxam, which imposes a greater nutrient limitation on production of brood. PMID- 24238720 TI - Effects of chronic elevated ozone concentration on the redox state and fruit yield of red pepper plant Capsicum baccatum. AB - Ozone (O3) is one of the most harmful air pollutants to crops, contributing to high losses on crop yield. Tropospheric O3 background concentrations have increased since pre-industrial times reaching phytotoxic concentrations in many world regions. Capsicum peppers are the second most traded spice in the world, but few studies concerning the O3 effects in this genus are known. Thereby, the aim of this work was to evaluate the effects of chronic exposure to elevated O3 concentrations in red pepper plant Capsicum baccatum L. var. pendulum with especial considerations on the leaf redox state and fruit yield. Fifteen C. baccatum plants were exposed to O3 in open-top chambers during fruit ripening (62 days) at a mean concentration of 171.6 ug/m(3) from 10:00 am to 4:00 pm. We found that O3 treated plants significantly decreased the amount and the total weight of fruits, which were probably a consequence of the changes on leaf oxidative status induced by ozone exposure. Ozone exposed plants increased the reactive oxygen species (ROS) levels on the leaves, which may be associated with the observed decrease on the activity of enzymatic antioxidant defense system, as well with lower levels of polyphenol and reduced thiol groups. Enhanced ROS production and the direct O3 reaction lead to biomacromolecules damages as seen in the diminished chlorophyll content and in the elevated lipid peroxidation and protein carbonylation levels. Through a correlation analysis it was possible to observe that polyphenols content was more important to protect pepper plants against oxidative damages to lipids than to proteins. PMID- 24238721 TI - Effects of triclosan on reproductive prarmeters and embryonic development of sea urchin, Strongylocentrotus nudus. AB - Triclosan (TCS, 2,4,4'-trichloro-2'-hydroxydiphenyl ether), a broad-spectrum antibacterial agent, is commonly found in the aquatic environment. In this study, we investigated TCS toxicity with pertaining to gamete viability, fertilization, and embryogenesis up to pluteus stage of the sea urchin, (Strongylocentrotus nudus). When the sperm and eggs were exposed to TCS (0-3.0 MUM), the viability of sperm was significantly decreased at molarities higher than 1 MUM of TCS. In addition, for exposure of 2.0 MUM TCS the viability of eggs was not influenced and none of the sperm was viable. Fertilization rate was significantly decreased when sperm were exposed to 0.5 and 1 MUM of TCS (p<0.001) and no fertilization was observed for the exposure of 1.5 MUM of TCS. In embryonic development, embryos are treated with higher than 1.0 MUM levels of TCS displayed arrested development. For TCS, the EC50 and LOECs values were 1.8, 1.49 and 0.99 MUM and 0.53, 0.62 and 0.39 MUM for sperm viability, fertilization rate, and larval development to pluteus, respectively. In the recovery test regarding normal development of arrested embryos based upon TCS exposure time, it was observed that embryos exposed to 1 MUM TCS for 15 h were normally recovered for normal development, while embryos with more than 30 h exposure were not recovered to normal larvae. Overall, the results of this study strongly suggest that the gametes and embryos of S. nudus can provide the basis for an effective bioassay, with a fast and sensitive means of evaluating TCS contamination in the marine ecosystem. PMID- 24238722 TI - Sequential therapy or triple therapy for Helicobacter pylori infection in Asians: systematic review and meta-analysis. AB - BACKGROUND AND OBJECTIVE: Eradication rate of Helicobacter pylori infection with triple therapy (TT) has declined in part to increased antibiotic resistance. Sequential therapy (ST) has shown promise in several meta-analyses. However, most of the studies included in previous meta-analyses were from Italy. The aim of this study was to compare the efficacy of ST with that of TT in Asia by performing a meta-analysis of studies from Asia. MATERIALS AND METHODS: We performed a comprehensive literature search for studies comparing the efficacy of ST with TT. Randomised controlled trials investigated in the Asian population were included. The odds ratios (OR) of eradicating H. pylori infection after ST compared with TT were pooled. The eradication rates were considered both on an intention-to-treat (ITT) and on a per-protocol basis (PP). RESULTS: A total of nine studies provided data on 3074 adult patients. The odds ratio (OR) for eradication of H. pylori with ST compared with TT was 1.768 (95% CI: 1.476-2.117, P=0.000) for ITT analysis and 1.997 (95% CI: 1.607-2.480, P=0.000) for PP analysis. The pooled eradication rates of ITT analysis was 81.3% (95% CI: 76.5 85.3) for the ST group and 70.8% (95% CI: 64.6-76.4) for the TT group. The pooled eradication rates of PP analysis was 87.6% (95% CI: 84.1-90.5) for the ST group and 77.1% (95% CI: 70.9-82.3) for the TT group. There was no difference in the rate of adverse events between ST and TT (OR 0.945, 95% CI: 0.874-1.238, P=0.658). CONCLUSION: ST appears to be better than TT in the eradication of H. pylori in Asia. These results suggest that ST may be a reasonable choice for first line therapy in Asia. PMID- 24238723 TI - Illuminating liver fibrosis with vitamin D. AB - Hepatic fibrosis results from the accumulation of extracellular matrix-producing myofibroblasts in the liver. The mechanisms leading to the activation of hepatic stellate cells (HSCs) into myofibroblasts have been well described. By contrast, few molecular pathways leading to myofibroblast deactivation have been documented. Recently, the vitamin D-VDR axis has been shown to modulate HSC activity through a complex mechanism involving epigenetic modifications induced by the SMAD pathway. PMID- 24238724 TI - Effects of short-term storage on the motility, oxidative stress, and ATP content of Persian sturgeon (Acipenser persicus) sperm. AB - The effective short-term storage of semen is essential when processing multiple sperm samples and when semen must be transported from collection sites to hatcheries for the fertilization of ova, or to laboratories for cryopreservation. In the present study, the spermatozoa of Persian sturgeon (Acipenser persicus) were used to evaluate the effects of short-term storage on quality parameters (the percentage of motile cells and the total period of sperm motility), oxidative stress indices, and the ATP content. Spermatozoa cells exhibited >50% motility during 6 days of storage where the average total duration of sperm motility varied from 376.42 +/- 80.86 s initially to 19.28 +/- 10.96 s after 6 days. No motile spermatozoa were recorded after 9 days of storage. The levels of oxidative stress indices (TBARS and CP) and antioxidant activity (SOD) increased significantly with the storage time. The ATP content also decreased significantly after 2 days of storage. The results of this study may facilitate successful reproduction management and cryopreservation protocols for this endangered fish. PMID- 24238725 TI - The effect of the number of transferred embryos, the interval between nuclear transfer and embryo transfer, and the transfer pattern on pig cloning efficiency. AB - To improve the efficiency of producing cloned pigs, we investigated the influence of the number of transferred embryos, the culturing interval between nuclear transfer (NT) and embryo transfer, and the transfer pattern (single oviduct or double oviduct) on cloning efficiency. The results demonstrated that transfer of either 150-200 or more than 200NT embryos compared to transfer of 100-150 embryos resulted in a significantly higher pregnancy rate (48 +/- 16, 50 +/- 16 vs. 29 +/ 5%, p<0.05) and average litter size (4.1 +/- 2.3, 7 +/- 3.6 vs. 2.5 +/- 0.5). In vitro culture of reconstructed embryos for a longer time (40 h vs. 20 h) resulted in higher (p<0.05) pregnancy rate (44 +/- 9 vs. 31 +/- 3%) and delivery rate (44 +/- 9 vs. 25 +/- 9%). Furthermore, double oviductal transfer dramatically increased pregnancy rate (83 +/- 6 vs. 27+8%, p<0.05), delivery rate (75 +/- 2 vs. 27+8%, p<0.05) and average litter size (6.5 +/- 2.8 vs. 2.6 +/- 1.2) compared to single oviductal transfer. Our study demonstrated that an improvement in pig cloning efficiency is achieved by adjusting the number and in vitro culture time of reconstructed embryos as well as the embryo transfer pattern. PMID- 24238726 TI - [Intra-abdominal hypertension: effects on the splanchnic circulation. Preliminary study in a model of ascites]. AB - INTRODUCTION: Intra-abdominal hypertension is defined as a rise in intra abdominal pressure leading to progressive dysfunction of the abdominal organs. OBJECTIVE: To evaluate the effects of intra-abdominal hypertension on the splanchnic circulation in a porcine animal model with a view to determining the diagnostic method of choice. MATERIAL AND METHODS: A total of 10 swine were divided into 2 groups: a control group and a group with an ascites pressure of 20mmHg. Transvesical and transperitoneal intra-abdominal pressures were registered, and the correlation between the measurements obtained was determined. Concentrations of lactic acid, alanine aminotransferase, glucose and gastric mucosal pH were also obtained. We registered the mean arterial and abdominal perfusion pressures, and the correlation of the latter with gastric mucosal pH and lactic acid concentrations. The parameters were registered for a total of 3hours. RESULTS: We observed a high correlation between transvesical and transperitoneal measurements of intra-abdominal pressure (R(2)=0.98). In the 20mmHg pressure group, lactic acid concentrations increased significantly at 180min (p<0.011). Gastric mucosal pH differed significantly between the 2 groups from the beginning of the study (p=0.004) and significantly decreased from 120min onward. Mean arterial and abdominal perfusion pressures gradually decreased during the trial, with early significant changes in the abdominal perfusion pressure (p=0.001), and a good correlation with the remaining study parameters. There were no significant changes in hepatic indicators. CONCLUSIONS: We believe the transvesical approach to be the technique of choice to determine intra abdominal pressure. Abdominal perfusion pressure is a sensitive marker of intra abdominal hypertension, and gastric mucosal pH is the first parameter to be affected. PMID- 24238727 TI - Comment on: High prevalence of vitamin D insufficiency in a United Kingdom urban morbidly obese population: Implications for testing and treatment. PMID- 24238728 TI - Bariatric surgery-induced weight loss: does it have any impact on serum cystatin C levels? PMID- 24238729 TI - Duodenal-jejunal bypass for the treatment of type 2 diabetes in Chinese patients with an average body mass index<24 kg/m2. AB - BACKGROUND: It is frequently reported that bariatric surgery often leads to resolution of type 2 diabetes mellitus (T2 DM). Limited experience with duodenal jejunal bypass (DJB) for the treatment of T2 DM has shown controversial results. We present the first study of DJB for T2 DM patients in China. The objective of this study was to evaluate the effects of DJB in nonobese Chinese patients with T2 DM. METHODS: From March 2009 to March 2011, a total of 10 T2 DM patients with an average body mass index (BMI) of 23.8 +/- 1.2 kg/m(2) were enrolled in the study. DJB was performed in all patients. BMI and glycometabolic parameters were collected at baseline and 1, 3, 6, 12, and 24 months postoperatively. Remission of T2 DM was defined as a glycosylated hemoglobin (HbA1c) level of<7% without diabetic medication. RESULTS: Remission of T2 DM was observed in 1 (10%) of 10 T2 DM patients at 6 months. Without increasing antihyperglycemic agents, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose, and HbA1c decreased significantly at each postoperative time point, compared with the preoperative baseline. BMI statistically decreased at 1 and 3 months, but did not reach statistical significance at 6, 12, and 24 months. CONCLUSIONS: DJB can improve glycemic control in nonobese T2 DM patients without significant weight loss but may not be effective enough to induce remission of T2 DM in nonobese Chinese patients. A larger sample size and more constrictive inclusion criteria may be required for better evaluation. PMID- 24238730 TI - Intestinal obstruction due to colonic volvulus in a patient with a previous bariatric surgery and intestinal malrotation. PMID- 24238731 TI - Metabolic surgery for diabetes mellitus after pancreatectomy. PMID- 24238732 TI - Management of gastrobronchial fistula after laparoscopic sleeve gastrectomy. AB - BACKGROUND: Gastric fistula (GF) is a serious complication after laparoscopic sleeve gastrectomy (LSG). Furthermore, gastrobronchial fistula (GBF) may appear some time after a primary LSG. The objective of this study was to characterize GBF after LSG and establish standardized treatment procedures. METHODS: All patients undergoing surgery for GBF after LSG at a public university medical center in France between November 2004 and January 2013 were included in this study. Surgical and perioperative care was standardized. The primary efficacy criterion was the complication rate. Secondary efficacy criteria were the mortality rate, surgical data, types of complications, and the length of stay (LOS) in hospital. RESULTS: Six patients were treated for GBF after LSG: 2 presented GBF after primary LSG performed in our institution and 4 had been referred by tertiary centers. The median (range) time to onset of GBF after LSG was 136 days (99-238 d). Preoperative refeeding was performed in 5 cases. The median time interval between the discovery of GBF and its surgical treatment was 31 days (7-137 d). Five patients underwent simultaneous abdominal and thoracic procedures. The abdominal procedures consisted of total gastrectomy (n = 1) and 60-cm Roux-en-Y gastrojejunal anastomosis (n = 6). There were no postoperative mortalities. Four postoperative complications occurred (66.6%), 2 of which were postoperative fistulas (33.3%) requiring revisional surgery. The median time to oral refeeding was 10 days (8-65 d) and the median LOS was 14 days (13-25 d). CONCLUSIONS: Our treatment of GBF is based on effective drainage with endoscopic procedures, allowing optimal preoperative refeeding before combined abdominal and thoracic surgery. For the abdominal procedure, we prefer a 60-cm Roux-en-Y gastrojejunal anastomosis to total gastrectomy, because the former is simpler and minimizes the long-term risk of postoperative malabsorption. PMID- 24238734 TI - A contextual clinical assessment for student midwives in Ireland. AB - Newly qualified midwives are required to be competent, safe practitioners providing high standards of care for mothers and babies. The role of educators is to teach for a sense of salience to enable students to meet this challenge with confidence and competence and to develop clinical reasoning skills. The difficulties of formulating an assessment that captures all these elements is challenging for all involved in midwifery education. Although the Objective Structured Clinical Skills Examination (OSCE) is a useful format for assessing aspects of practice, it does not capture the students' simultaneous interaction with a woman and her baby while performing routine care where a variety of issues can be assessed in a contextual way. In University College Cork, a clinical assessment has been developed whereby students perform an aspect of clinical care followed by a low-fidelity simulated pregnancy complication or emergency appropriate to the student's level of learning. The students demonstrate their level of knowledge and skills in a contextual environment. Assessment in practice is challenging for midwives and educators but is essential in determining fitness for entry into the profession. PMID- 24238733 TI - Improvement in gastroesophageal reflux disease symptoms after various bariatric procedures: review of the Bariatric Outcomes Longitudinal Database. AB - BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) in the morbidly obese population is as high as 45%. The objective of this study was to compare the efficacy of various bariatric procedures in the improvement of GERD. METHODS: The Bariatric Outcomes Longitudinal Database is a prospective database of patients who undergo bariatric surgery by a participant in the American Society of Metabolic and Bariatric Surgery Center of Excellence program. GERD is graded on a 6-point scale, from 0 (no history of GERD) to 5 (prior surgery for GERD). Patients with GERD severe enough to require medications (grades 2, 3, and 4) from June 2007 to December 2009 are identified; the resolution of GERD is noted based on 6-month follow-up. RESULTS: Of a total of 116,136 patients, 36,938 patients had evidence of GERD preoperatively. After excluding patients undergoing concomitant hiatal hernia repair or fundoplication, there were 22,870 patients with 6-month follow-up. Mean age was 47.6+/-11.1 years, with an 82% female population. Mean BMI was 46.3+/-8.0 kg/m(2). Mean preoperative GERD score for patients with Roux-en-Y gastric bypass (RYGB) was 2.80+/-.56, and mean postoperative score was 1.33+/-1.41 (P<.0001). Similarly, adjustable gastric banding (AGB, 2.77+/-.57 to 1.63+/-1.37, P<.0001) and sleeve gastrectomy (SG, 2.82+/-.57 to 1.85+/-1.40, P<.0001) had significant improvement in GERD score. GERD score improvement was best in RYGB patients (56.5%; 7955 of 14,078) followed by AGB (46%; 3773 of 8207) and SG patients (41%; 240 of 585). CONCLUSION: All common bariatric procedures improve GERD. Roux-en-Y gastric bypass is superior to adjustable gastric banding and sleeve gastrectomy in improving GERD. Also, the greater the loss in excess weight, the greater the improvement in GERD score. PMID- 24238735 TI - Associations between baccalaureate nursing students' perceptions of educational environment and HESI scores and GPA. AB - BACKGROUND: Students' perceptions of their educational environment have been found to be related to their approaches to learning and learning outcomes. Educational environment is just beginning to be researched in nursing education with the vast majority of studies focusing on the clinical educational environment. Perception of educational environment has been shown to influence student implementation of a specific learning style and influences educational outcomes such as program completion and GPA. There is a need for sound research that explores the relationship, if any, between perceptions of environment and outcomes. OBJECTIVE: To explore the relationship between baccalaureate nursing student (BSN) perception of educational environment (SPEE) and objective learning outcomes. DESIGN: Retrospective correlational descriptive study. SETTING: Private School of Nursing in the Southwest. PARTICIPANTS: Convenience sample of 62 graduating baccalaureate students. METHODS: All graduating BSN students were invited to complete the Dundee Ready Education Environment Measure (DREEM) through the online survey application Qualtrics. A total of 62 students completed the DREEM survey. These results were compared with each student's GPA and HESI score. RESULTS: A total of 62 students completed the survey for an overall response rate of 57%. There was no correlation between total SPEE and nursing grade point average (NGPA) or HESI exit scores. CONCLUSIONS: Based on this study at this institution, it appears that students' performance was not influenced by SPEE. One of the major implications of this study is the possibility that an "acceptable" SPEE (one that is neither exceptional nor terrible) may not significantly influence student outcomes. Exploring this relationship has theoretical as well as practical implications as educators seek to determine the effectiveness of educational interventions. Student perception of learning environment is measured in various ways at the majority of institutions. It has been assumed that an educational environment that is ranked high by students result in increased learning. However, as the science of nursing education advances, educators need to determine if and how these perceptions relate to actual learning outcomes. As academicians, we need to be concerned with the relationship between learning outcomes and environment in order to create the most effective learning environment. PMID- 24238737 TI - Electrocardiographic ST-segment monitoring during controlled occlusion of coronary arteries. AB - BACKGROUND: Ischemia monitoring cannot always be performed by 12-lead ECG. Hence, the individual performance of the ECG leads is crucial. No experimental data on the ECG's specificity for transient ischemia exist. METHODS: In 45 patients a 19 lead ECG was registered during a 1-minute balloon occlusion of a coronary artery (left anterior descending artery [LAD], right coronary artery [RCA] or left circumflex artery [LCX]). ST-segment shifts and sensitivity/specificity of the leads were measured. RESULTS: During LAD occlusion, V3 showed maximal ST-segment elevation (0.26mV [IQR 0.16-0.33mV], p=0.001) and sensitivity/specificity (88% and 80%). During RCA occlusion, III showed maximal ST-elevation (0.2mV [IQR 0.09 0.26mV], p=0.004), aVF had the best sensitivity/specificity (85% and 68%). During LCX occlusion, V6 showed maximal ST-segment elevation (0.04mV [IQR 0.02-0.14mV], p=0.005), and sensitivity/specificity was (31%/92%) but could be improved (63%/72%) using an optimized cut-off for ischemia. CONCLUSION: V3, aVF and V6 show the best performance to detect transient ischemia. PMID- 24238738 TI - Adsorption of selenite and selenate by nanocrystalline aluminum oxide, neat and impregnated in chitosan beads. AB - Nanocrystalline metal oxide impregnated chitosan beads (MICB) were successfully developed with nanocrystalline aluminum oxide (n-Al2O3) to form n-Al2O3 impregnated chitosan beads (AICB). AICB were able to simultaneously adsorb inorganic aqueous selenite and selenate more effectively than n-Al2O3 or chitosan alone. For completeness, adsorption performance was also compared to n-TiO2, a widely studied adsorbent for selenium, and n-TiO2 impregnated chitosan beads (TICB). For the selenite system, n-Al2O3 was the primary active adsorbent responsible for removal as chitosan has a low affinity for selenite. For selenate, however, chitosan was the primary active adsorbent. The association constants for the adsorbent/adsorbate complexes and the relative amounts in which they are present supported this hypothesis. The association constants for selenate binding on n-Al2O3 and chitosan were 1.215 * 10(-2) and 3.048 * 10(-3), respectively, and the association constants for selenite binding on n-Al2O3 and chitosan were 1.349 * 10(-2) and 1.990 * 10(-4), respectively. For systems with coexisting selenite and selenate, AICB is potentially the most robust option as it maintained the most consistent performance regardless of fractionation of the selenium species. Kinetic studies and equilibrium isotherms were completed and effectively modeled using pseudo-second order kinetics and Langmuir adsorption theory, making it the first comprehensive systematic study of neat n-Al2O3 and AICB for selenium adsorption. pH significantly impacted adsorption due to changes in the adsorbent surface charge; increasing pH corresponded with decreasing adsorbent performance, beginning at approximately pH 6.5-7 for AICB. The trend in performance due to the effect of pH indicated that selenate binds to the amine group in chitosan, as suggested by other studies. In addition, increasing background sulfate concentration was found to negatively impact adsorption efficacy for both selenite, and more significantly, selenate, as sulfate is known to compete with selenium oxyanions due to their similar structures. The results indicate that, in order to maintain consistent removal in more realistic systems, a pre-treatment process to manage sulfate will be necessary as indicated for other adsorbents implemented for selenium adsorption in aqueous systems. PMID- 24238736 TI - Smoking and microRNA dysregulation: a cancerous combination. AB - MicroRNAs (miRNAs) are post-transcriptional gene regulators that are differentially expressed in several pathophysiological conditions including cancer. They impact the disease course by modulating an array of putative target gene(s). Interestingly, there is a strong correlation between the various miRNAs target(s) and the smoking-regulated genes in cancer. This review article provides an insight into the current status of smoking-induced miRNAs and their genetic/epigenetic regulation in smoking-associated cancers, with a major focus on lung cancer (LC). Furthermore, it discusses the role of miRNAs in smoking mediated oncogenic events in cancer and explores the diagnostic/prognostic potential of miRNA-based biomarkers and their efficacy as therapeutic targets. PMID- 24238739 TI - Reevaluation of health risk benchmark for sustainable water practice through risk analysis of rooftop-harvested rainwater. AB - Health risk concerns associated with household use of rooftop-harvested rainwater (HRW) constitute one of the main impediments to exploit the benefits of rainwater harvesting in the United States. However, the benchmark based on the U.S. EPA acceptable annual infection risk level of <=1 case per 10,000 persons per year (<=10(-4) pppy) developed to aid drinking water regulations may be unnecessarily stringent for sustainable water practice. In this study, we challenge the current risk benchmark by quantifying the potential microbial risk associated with consumption of HRW-irrigated home produce and comparing it against the current risk benchmark. Microbial pathogen data for HRW and exposure rates reported in literature are applied to assess the potential microbial risk posed to household consumers of their homegrown produce. A Quantitative Microbial Risk Assessment (QMRA) model based on worst-case scenario (e.g. overhead irrigation, no pathogen inactivation) is applied to three crops that are most popular among home gardeners (lettuce, cucumbers, and tomatoes) and commonly consumed raw. The infection risks of household consumers attributed to consumption of these home produce vary with the type of produce. The lettuce presents the highest risk, which is followed by tomato and cucumber, respectively. Results show that the 95th percentile values of infection risk per intake event of home produce are one to three orders of magnitude (10(-7) to 10(-5)) lower than U.S. EPA risk benchmark (<=10(-4) pppy). However, annual infection risks under the same scenario (multiple intake events in a year) are very likely to exceed the risk benchmark by one order of magnitude in some cases. Estimated 95th percentile values of the annual risk are in the 10(-4) to 10(-3) pppy range, which are still lower than the 10(-3) to 10(-1) pppy risk range of reclaimed water irrigated produce estimated in comparable studies. We further discuss the desirability of HRW for irrigating home produce based on the relative risk of HRW to reclaimed wastewater for irrigation of food crops. The appropriateness of the <=10(-4) pppy risk benchmark for assessing safety level of HRW-irrigated fresh produce is questioned by considering the assumptions made for the QMRA model. Consequently, the need of an updated approach to assess appropriateness of sustainable water practice for making guidelines and policies is proposed. PMID- 24238740 TI - Are the intertidal fish highly resistant to UV-B radiation? A study based on oxidative stress in Girella laevifrons (Kyphosidae). AB - Sea chub, Girella laevifrons, is a coastal fish that inhabits high intertidal rockpools along the coast of Chile. The intertidal pools where the juveniles live, are an extreme environment with high levels of ultraviolet (UV) radiation, becoming harmful to the organisms, due to oxidative stress generated by reactive oxygen species. For this reason organisms develop adaptations that allow them to survive in this complex environment. The search of biomonitor species, sensitive to UV radiation is very important in aquatic ecosystems, mainly in the southern hemisphere where depletion of the ozone layer and the consequent increase of UV radiation, have become an environmental problem. The aim of this study was to evaluate the effect of ultraviolet radiation in G. laevifrons and its possible use as UV-B radiation biomonitor specie in intertidal systems, which are very important for the Chilean fisheries. The effect of UV radiation exposure on juvenile G. laevifrons was measured through oxidative stress parameters. Catalase's activity increased with the time of exposure, unlike superoxide dismutase's activity which peaked at 2h, decreasing towards the 5th hour of irradiation. The superoxide dismutase activity in muscle tissue did not show significant differences. The lipid peroxidation and DNA damage increased in relation to exposition times. Tissue muscle's DNA damage was shown only at 5h of exposure. Significant differences between the two organs in the antioxidant capacity were observed, the liver of G. laevifrons exhibited the higher antioxidant capacity. It can be concluded that this specie exhibits effective protection mechanisms against UV radiation exposure and it is not appropriate specie as a biomonitor in intertidal systems. PMID- 24238741 TI - In vivo and in vitro genotoxicity assessment of 2-methylisoborneol, causal agent of earthy-musty taste and odor in water. AB - The water eutrophication process by phosphorus and nitrogen allows cyanobacteria blooms which promote, among other effects, the generation and release of the metabolite 2-methylisoborneol (2-MIB) in the environment. This substance has been shown to be recalcitrant to conventional water treatment, degrading water quality. Considering the limited number of studies on the biological effects of 2 MIB in eukaryotic organisms, the present study assessed the genotoxicity of 2-MIB using the in vitro comet assay and cytokinesis block-micronucleus (CBMN-Cytome) assay on Chinese Hamster Ovary (CHO) cells and the in vivo Drosophila melanogaster Somatic Mutation and Recombination Test (SMART). The results showed that 2-MIB (125, 250 and 500 ug/mL) was unable to induce gene and chromosome mutations or events associated with mitotic recombination in the SMART. Similarly, four different concentrations (7.5, 15, 30 and 60 ug/mL) of 2-MIB did not induce increments in frequencies of micronuclei, nuclear buds, and nucleoplasmatic bridges in the CBMN-Cytome assay. In the comet assay, the positive results were restricted to the highest dose, 60 ug/mL of 2-MIB. The results obtained may help evaluate the genotoxic profile of extracellular algal products. PMID- 24238742 TI - Development of a chronic, early life-stage sub-lethal toxicity test and recovery assessment for the tropical zooxanthellate sea anemone Aiptasia pulchella. AB - There is an urgent need to identify additional tropical marine species and develop sensitive sub-lethal and chronic toxicity test methods for routine ecotoxicology. The tropical symbiotic sea anemone Aiptasia pulchella is a suitable species for use in ecotoxicology and here we have assessed the effects of trace metal exposures on the development of asexually produced A. pulchella pedal lacerates to a juvenile stage. Concentrations of 55 ug/L for cadmium, 262 ug/L for cobalt, 5 ug/L for copper, and 269 ug/L for zinc were estimated to inhibit normal development by 50 percent after 8-d exposures, and are among the most sensitive available toxicity estimates for marine organisms. This work illustrates the potential value of this species and sub-lethal toxicological endpoint for routine ecotoxicology in tropical marine environments. PMID- 24238745 TI - Application of neurally adjusted ventilatory assist in neonates. AB - Neurally adjusted ventilatory assist (NAVA) uses the electrical activity of the diaphragm (Edi) as a neural trigger to synchronize mechanical ventilatory breaths with the patient's neural respiratory drive. Using this signal enables the ventilator to proportionally support the patient's instantaneous drive on a breath-by-breath basis. Synchrony can be achieved even in the presence of significant air leaks, which make this an attractive choice for invasive and non invasive ventilation of the neonate. This paper describes the Edi signal, neuroventilatory coupling, and patient-ventilator synchrony including the functional concept of NAVA. Safety features, NAVA terminology, and clinical application of NAVA to unload respiratory musculature are presented. The use of the Edi signal as a respiratory vital sign for conventional ventilation is discussed. The results of animal and adult studies are briefly summarized and detailed descriptions of all NAVA-related research in pediatric and neonatal patients are provided. Further studies are needed to determine whether NAVA will have significant impact on the overall outcomes of neonates. PMID- 24238743 TI - Landmark matching based retinal image alignment by enforcing sparsity in correspondence matrix. AB - Retinal image alignment is fundamental to many applications in diagnosis of eye diseases. In this paper, we address the problem of landmark matching based retinal image alignment. We propose a novel landmark matching formulation by enforcing sparsity in the correspondence matrix and offer its solutions based on linear programming. The proposed formulation not only enables a joint estimation of the landmark correspondences and a predefined transformation model but also combines the benefits of the softassign strategy (Chui and Rangarajan, 2003) and the combinatorial optimization of linear programming. We also introduced a set of reinforced self-similarities descriptors which can better characterize local photometric and geometric properties of the retinal image. Theoretical analysis and experimental results with both fundus color images and angiogram images show the superior performances of our algorithms to several state-of-the-art techniques. PMID- 24238744 TI - Transcriptome signatures of class I and III stress response deregulation in Lactobacillus plantarum reveal pleiotropic adaptation. AB - BACKGROUND: To cope with environmental challenges bacteria possess sophisticated defense mechanisms that involve stress-induced adaptive responses. The canonical stress regulators CtsR and HrcA play a central role in the adaptations to a plethora of stresses in a variety of organisms. Here, we determined the CtsR and HrcA regulons of the lactic acid bacterium Lactobacillus plantarum WCFS1 grown under reference (28 degrees C) and elevated (40 degrees C) temperatures, using ctsR, hrcA, and ctsR-hrcA deletion mutants. RESULTS: While the maximum specific growth rates of the mutants and the parental strain were similar at both temperatures (0.33 +/- 0.02 h(-1) and 0.34 +/- 0.03 h(-1), respectively), DNA microarray analyses revealed that the CtsR or HrcA deficient strains displayed altered transcription patterns of genes encoding functions involved in transport and binding of sugars and other compounds, primary metabolism, transcription regulation, capsular polysaccharide biosynthesis, as well as fatty acid metabolism. These transcriptional signatures enabled the refinement of the gene repertoire that is directly or indirectly controlled by CtsR and HrcA of L. plantarum. Deletion of both regulators, elicited transcriptional changes of a large variety of additional genes in a temperature-dependent manner, including genes encoding functions involved in cell-envelope remodeling. Moreover, phenotypic assays revealed that both transcription regulators contribute to regulation of resistance to hydrogen peroxide stress. The integration of these results allowed the reconstruction of CtsR and HrcA regulatory networks in L. plantarum, highlighting the significant intertwinement of class I and III stress regulons. CONCLUSIONS: Taken together, our results enabled the refinement of the CtsR and HrcA regulatory networks in L. plantarum, illustrating the complex nature of adaptive stress responses in this bacterium. PMID- 24238747 TI - Toward lung protective ventilation during general anesthesia: a new challenge. PMID- 24238746 TI - Complete recovery after out-of-hospital cardiac arrest with prolonged (59 min) mechanical cardiopulmonary resuscitation, mild therapeutic hypothermia and complex percutaneous coronary intervention for ST-elevation myocardial infarction. AB - We report on a 68 years old survivor of an out-of-hospital cardiac arrest with favorable neurological outcome following prolonged cardiopulmonary resuscitation (CPR 59 min) until return of spontaneous circulation (ROSC) due to ST-elevation myocardial infarction (STEMI). The case demonstrates the beneficial effect of an optimal rescue chain including basic life support performed by trained bystanders, short response time of the emergency medical service, uninterrupted CPR during transportation using a mechanical chest compression system (LUCAS(r)), in combination with optimal intensive care management of cardiogenic shock after ROSC including multivessel emergency percutaneous coronary intervention (PCI) and intravascular therapeutic hypothermia (Coolgard(r)-System). PMID- 24238748 TI - [Lower limb arterial disease and renal artery stenosis]. AB - Peripheral arterial disease (PAD) refers to the atherosclerotic involvement of non-coronary and extracranial arteries, including visceral arteries, the aorta and its branches and the arteries of the limbs. PAD usually refers exclusively to atherosclerosis of the limbs (in particular the lower limbs). Age, male sex, smoking and diabetes, as well as hypertension and dyslipidemia, are the most relevant risk factors for the development of PAD. PAD is frequently associated with coronary heart disease and stroke. PAD patients have increased risk of developing cardiovascular complications (coronary disease, stroke) and total and cardiovascular mortality, even after adjustment by conventional risk factors. Despite this PAD exhibit a worse control of risk factors. This opens up an important opportunity to optimize their control, which can result in an improvement of the prognosis of patients with PAD. Ischemic nephropathy includes a constellation of disorders that are frequently associated: hypertension, renal failure and renal artery stenosis (RAS). RAS risk factors are similar to those of PAD. Recent studies have shown that renal revascularization is not associated with improvement in blood pressure control, preservation of renal function or reduction of cardiovascular events in most patients. Therefore, revascularization should be reserved for selected cases on an individual basis. In all cases, a strict control of vascular risk factors should be attempted. PMID- 24238749 TI - [Ischaemic heart disease]. AB - In the year 2011, cardiovascular diseases were responsible of 31.2% of total deaths in Spain. The absolute number of cases of acute coronary syndrome in this year will be approximately 115,752 cases (95%CI: 114,822-116,687). The prevalence of stable angina in the population aged 25-74 years is 2.6% in men and 3.5% in women. Cardiovascular diseases were in the year 2011 the first cause of hospitalizations representing 14.1% of the total hospitalizations. Diagnose of ischaemic heart disease and acute myocardial infarction were responsible of 110,950 and 50,064 hospitalizations, respectively. In the year 2003, the hospitalization rate was 314 while in the year 2011 was 237 per 100,000, a reduction of 24.4%. The average cost of hospitalization due to ischaemic heart disease in 1997 was 3,093.7euros while in the year 2011 was 7,028.71euros. Cardiovascular mortality rates have decreased from 2007 to 2011, showing a relative reduction of 7% in women and 8% in men. With regard to myocardial infarction, it was observed a relative reduction of 17% in men and 20% in women. According to EUROASPIREIII survey done in 8,966 patients with ischaemic heart disease in Europe, 17% of patients were still smokers, 35% were obese, 56% has uncontrolled blood pressure, 51% has raised blood cholesterol and 25% were diabetics. With regard to drugs utilisation, 91% were treated with antiplatelets agents, 80% with beta blockers, 71% with ACE inhibitors/ARBs. PMID- 24238750 TI - Weight-bearing asymmetries during Sit-To-Stand in patients with mild-to-moderate hip osteoarthritis. AB - The Sit-To-Stand (STS) transition is a mechanically demanding task that may pose particular challenges for individuals with lower limb osteoarthritis (OA). Biomechanical features of STS have been investigated in patients with OA, but not in patients with early stage hip OA. The purpose of this study was to explore inter-limb weight-bearing asymmetries (WBA) and selected kinematic and kinetic variables during STS in patients with mild-to-moderate hip OA compared with healthy controls. Twenty-one hip OA patients and 23 controls were included in the study. Sagittal and frontal plane kinematic and kinetic data were collected using an eight-camera motion analysis system synchronized with two force plates embedded in the floor. There were no distinctive biomechanical alterations in sagittal or frontal plane kinematics or kinetics, movement time, or time to reach peak ground reaction force (GRF) in hip OA patients compared with controls. However, the hip OA patients revealed a distinct pattern of WBA compared with the controls, in unloading their involved limb by 18.4% at peak GRF. These findings indicate that patients with early stage hip OA are not yet forced into a stereotypical movement strategy for STS; however, the observed pattern of WBA requires clinical attention. PMID- 24238751 TI - Comparison of superficial surgical site infection between delayed primary and primary wound closures in ruptured appendicitis. AB - BACKGROUND: Delayed primary (DPC) and primary (PC) wound closures have been applied in ruptured appendicitis, but results were controversial. This study aims at comparing the rate of superficial surgical site infection (SSI) in ruptured appendicitis between DPC and PC. METHODS: A retrospective cohort of ruptured appendicitis was conducted between October 2006 and November 2009. Demographic, operative findings and postoperative infection data were retrieved. The superficial SSI rates between groups were compared using an exact test. An odds ratio of SSI was then estimated. RESULTS: One-hundred and twenty eight patients with ruptured appendicitis were eligible and their data were retrieved; 115 (90%) patients had received DPC and 13 (10%) patients had received PC. The SSI rate was much lower in PC patients than in DPC patients, i.e., 7.7% [95% confidence interval (CI): 0.02, 36.0] versus 27.8% (95% CI: 19.9, 37.0), respectively. There was an approximately 72% lower risk of SSI in the PC group than in the DPC group, but this did not reach statistical significance (p = 0.18). CONCLUSION: Our study suggested that PC does not increase risk of SSI in low SSI risk patients with ruptured appendicitis. DPC should not be routinely done. PMID- 24238752 TI - Aortic root geometry in patients with aortic stenosis assessed by real-time three dimensional transesophageal echocardiography. AB - BACKGROUND: The authors hypothesized that aortic root geometry is different between bicuspid and tricuspid aortic stenosis (AS) that can be assessed using real-time three-dimensional (3D) transesophageal echocardiography. The aims of this study were (1) to validate the accuracy of 3D transesophageal echocardiographic measurements of the aortic root against multidetector computed tomography as a reference, (2) to determine the difference of aortic root geometry between patients with tricuspid and bicuspid AS, and (3) to assess its impact on pressure recovery. METHODS: In protocol 1, 3D transesophageal echocardiography and contrast-enhanced multidetector computed tomography were performed in 40 patients. Multiplanar reconstruction was used to measure the aortic annulus, the sinus of Valsalva, and the sinotubular junction area, as well as the distance and volume from the aortic annulus to the sinotubular junction. In protocol 2, the same 3D transesophageal echocardiographic measurements were performed in patients with tricuspid AS (n = 57) and bicuspid AS (n = 26) and in patients without AS (n = 32). The energy loss coefficient was also measured in patients with AS. RESULTS: In protocol 1, excellent correlations of aortic root geometric parameters were noted between the two modalities. In protocol 2, compared with patients without AS, those with tricuspid AS had smaller both sinotubular junction areas and longitudinal distances, resulting in a 23% reduction of aortic root volume. In contrast, patients with bicuspid AS had larger transverse areas and longitudinal distances, resulting in a 30% increase in aortic root volume. The energy loss coefficient revealed more frequent reclassification from severe AS to moderate AS in patients with tricuspid AS (17%) compared with those with bicuspid AS (10%). CONCLUSIONS: Three-dimensional transesophageal echocardiography successfully revealed different aortic root morphologies between tricuspid and bicuspid AS, which have different impacts on pressure recovery. PMID- 24238753 TI - Age-related normal range of left ventricular strain and torsion using three dimensional speckle-tracking echocardiography. AB - BACKGROUND: Three-dimensional (3D) speckle-tracking echocardiography (STE) is an emerging technology used to quantify left ventricular (LV) function. However, the accuracy and normal values of LV strain and twist using 3D STE have not been established in a large group of normal subjects. The aims of this study were to (1) to evaluate the accuracy of 3D STE analysis of LV strain against a cardiac magnetic resonance (CMR) reference and (2) to establish age-related normal values of LV strain and torsion using real-time 3D echocardiographic (RT3DE) images. METHODS: In protocol 1, RT3DE data sets and CMR images were acquired on the same day in 19 patients referred for clinically indicated CMR. Global LV longitudinal, circumferential, and radial strain was compared between the two modalities. In protocol 2, global and regional strain and twist and torsion were measured in 313 healthy subjects using 3D STE. RESULTS: In protocol 1, good correlations for each LV strain component were noted between RT3DE imaging and CMR (r = 0.61-0.86, P < .001). In protocol 2, normal global longitudinal, circumferential, radial, and 3D strain were -20.3 +/- 3.2%, -28.9 +/- 4.6%, 88.0 +/- 21.8%, and -37.6 +/- 4.8%, respectively. A significant age dependency was observed for global longitudinal and 3D strain. Aging also affected LV torsion: the lowest values were found in children and adolescents, and values subsequently increased with age, while further aging was associated with a gradual reduction in basal rotation accompanied by an increase in apical rotation. CONCLUSIONS: This study provides initial validation of 3D strain analysis from RT3DE images and reference values of normal 3D LV strain and torsion. The age-related differences in LV strain and torsion may reflect myocardial maturation and aging. PMID- 24238754 TI - Identification of predictive biomarkers for early diagnosis of larynx carcinoma based on microRNA expression data. AB - The abnormal expression of microRNAs (miRNAs) plays a key role in tumorigenesis. In order to identify potential miRNA biomarkers for early diagnosis of larynx carcinoma, we employed a miRNA microarray technique and applied bioinformatic algorithms to characterize miRNA classifiers in early larynx carcinoma and normal esophageal mucosa tissue samples from 69 patients who were selected retrospectively for this study. We identified 47 miRNAs that were significantly differentially expressed in primary larynx tumor tissues compared to normal tissues using a SAM algorithm. Of these, 30 were up-regulated and 17 down regulated in early larynx cancer, including hsa-miR-657, which was overexpressed, and hsa-miR-1287, which was underexpressed. These two candidate miRNA biomarkers were combined as a single classifier to recognize the biological characteristics in early larynx carcinoma. Real-time quantitative reverse-transcription PCR validated the microarray results in both trial and test samples. The hsa-miR-657 hsa-miR-1287 classifier displayed high sensitivity and specificity for discriminating between early larynx carcinoma and normal mucosa tissues, suggesting they may be suitable as potential predictive biomarkers for the early diagnosis of larynx carcinoma. PMID- 24238755 TI - Why global risk scores fail to detect at-risk young women and men with acute coronary syndromes. PMID- 24238756 TI - Characteristics and evidence-based management of stable coronary artery disease patients in Canada compared with the rest of the world: insights from the CLARIFY registry. AB - BACKGROUND: Previous Canadian high vascular risk registries have demonstrated suboptimal goal-directed reductions in cardiovascular risk factors and underutilization of guideline-recommended therapies in part because of physician underestimation of cardiovascular risk. METHODS: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled 33,438 stable coronary artery disease patients in 45 countries. In Canada, supplemental information was obtained specifying reasons that patients were not taking guideline-recommended medications. RESULTS: In Canada, 1232 patients (9 provinces, 110 physicians) were enrolled and in comparison with the rest of the world, there were several differences in cardiovascular risk factors and medical history; in addition, the Canadian cohort had undergone less percutaneous coronary intervention, but more coronary artery bypass grafting. Among the Canadian cohort, many still continue to smoke (13%) and many do not meet secondary prevention targets for waist circumference (54%), body mass index (81%), physical activity (71%), cholesterol (43%), and systolic blood pressure (20%). Nevertheless, the use of guideline-recommended cardiovascular therapy was high and >90% reported partial/full financial coverage for medications. The number of patients not receiving guideline-recommended therapies because of apparent underestimation of risk was particularly low for antiplatelet agents (2%), beta-blockers (11%), and lipid-lowering therapies (1%). CONCLUSIONS: Canadian patients with stable coronary artery disease did not meet several guideline-recommended secondary prevention targets, despite high use of evidence based therapy, extensive financial coverage for these medications, and low physician underestimation of risk. Additional work is needed to identify and address the remaining barriers to effective risk factor control. PMID- 24238758 TI - Preventing cardiovascular events after percutaneous coronary intervention: have we been asleep at the switch? PMID- 24238757 TI - Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome. AB - BACKGROUND: Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS). METHODS: Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores. RESULTS: Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men. CONCLUSIONS: Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS. PMID- 24238759 TI - Acute left main coronary occlusion caused by stent fracture, peri-stent aneurysm formation, and very-late stent thrombosis: revisiting the dark side of drug eluting stents. AB - A patient presented with acute distal left main occlusion as a result of very late stent thrombosis of 2 drug-eluting stents. Intravascular ultrasound imaging confirmed the presence of a peri-stent aneurysm coupled with malapposition at the site of a stent fracture, reflecting an abnormal vascular response to drug eluting stents. PMID- 24238760 TI - Lenalidomide monotherapy in chemotherapy-naive, castration-resistant prostate cancer patients: final results of a phase II study. AB - BACKGROUND: We investigated the activity of lenalidomide, which has antiangiogenic, antineoplastic, and immunomodulatory properties, in chemotherapy naive, castration-resistant prostate cancer (CRPC) patients. PATIENTS: Patients received 25 mg/d lenalidomide for 21 days in 28-day cycles, until disease progression or unacceptable toxicity developed. Endpoints included overall response rate and clinical benefit (overall response + stable disease), toxicity, time to radiographic progression, and time to prostate-specific antigen (PSA) progression, overall survival, and quality of life. RESULTS: Thirty-two patients were enrolled in the study; of these, 77% (n = 25) had Gleason scores >= 7. The median age was 74 years (58-89 y), the median PSA level was 66 ng/mL (2-919 ng/mL), and 5 of 32 patients (17%) had liver or lung involvement. The median number of lenalidomide cycles was 3 (1-16 cycles). Stable disease was seen in 20 patients, for a clinical benefit rate of 63%. The median time to radiographic progression was 4 months (2-16 mo); the median overall survival was 20 months. Of 27 PSA-evaluable patients, 13 (48%) had a decline in PSA level; 3 (11%) had > 50% PSA decrease; the median time to PSA progression was 3 months (2-9 mo). Grade 3/4 hematologic toxicities were the most common adverse events without adverse impact on quality of life. Serious adverse events occurred in 14 patients (44%), including 1 patient (3%) with a rash definitely related to lenalidomide. CONCLUSION: Lenalidomide monotherapy demonstrates modest activity in chemotherapy naive CRPC. PMID- 24238761 TI - Sentinel lymph node biopsy in patients with microinvasive breast cancer: a systematic review and meta-analysis. AB - BACKGROUND: The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer. METHODS: We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity. FINDINGS: A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%-4.6%), 4.0% (95% CI 2.7%-5.5%), and 2.9% (95% CI: 1.6%-4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate. INTERPRETATION: The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized. PMID- 24238762 TI - Radiologic assessment of earliest, best, and plateau response of gastrointestinal stromal tumors to neoadjuvant imatinib prior to successful surgical resection. AB - BACKGROUND: To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST. MATERIALS AND METHODS: In this IRB approved retrospective study, we included all 20 patients (10 women; mean age 61 years, range 30-83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter [LAD] and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (time point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging. RESULTS: Median tumor size at baseline was 7.2 cm (range, 3.0-31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16-36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7-26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7 26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31 48%) and 83% (IQR, 63-87%), (median interval = 28 weeks; IQR, 18-37 weeks), at which point 10 tumors were resected. Plateau response (45% [IQR, 35-45%] LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26-41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response. CONCLUSION: Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial. PMID- 24238763 TI - Esophageal cancer in Iran; a population-based study regarding adequacy of cancer surgery and overall survival. AB - AIMS: Prognosis of esophageal cancer (EC) is poor. Population-based studies regarding EC survival and adequacy of cancer surgery (ACS) from developing countries are lacking. We aimed to evaluate EC patients' survival and ACS in a population-based setting for the first time from Iran. METHODS: We randomly selected 409 cases from all 3048 newly diagnosed EC patients who were registered in the nationwide cancer registry in calendar year 2005-2006 and followed them until 2009. An expert panel in Cancer Institute of Iran reviewed adequacy of esophageal cancer surgery on a national basis. RESULTS: Overall three-year survival rate was 17%. The median (95% CI) survival time of all patients and cases who underwent surgery alone were 8.5 (6.9-10.1) and 6.0 (3.1-8.9) months, respectively. The hospital mortality was 27.8% among the operated patients. Only 6.8% of cases had documented free circumferential resection margin and merely 4.0% of patients experienced resection of more than 15 lymph nodes during surgery. CONCLUSIONS: In Iran, the overall survival of EC patients with different treatment modalities are slightly less than those reported from high-income countries, but cases with surgery alone as the main treatment had worse outcome compared with their counterparts in developed countries. Surgery with curative intent has not been performed in most cases in Iran. It seems current clinical outcome of EC patients could be improved with surgical quality improvement and/or more use of chemoradiation in Iran. PMID- 24238764 TI - Infant sensitivity to speaker and language in learning a second label. AB - Two experiments examined when monolingual, English-learning 19-month-old infants learn a second object label. Two experimenters sat together. One labeled a novel object with one novel label, whereas the other labeled the same object with a different label in either the same or a different language. Infants were tested on their comprehension of each label immediately following its presentation. Infants mapped the first label at above chance levels, but they did so with the second label only when requested by the speaker who provided it (Experiment 1) or when the second experimenter labeled the object in a different language (Experiment 2). These results show that 19-month-olds learn second object labels but do not readily generalize them across speakers of the same language. The results highlight how speaker and language spoken guide infants' acceptance of second labels, supporting sociopragmatic views of word learning. PMID- 24238765 TI - Neo-valvuloplasty for lymphatic supermicrosurgery. PMID- 24238766 TI - Response from the authors of 'Treatment of infantile haemangiomas with atenolol: comparison with a historical propranolol group'. PMID- 24238767 TI - [Important differences between faculties of medicine. Implications for family and community medicine]. AB - OBJECTIVE: To determine if there are significant differences between universities in the proclivity to choose Family and Community Medicine (FCM), given the constraints imposed by the number of choice. To test the hypothesis that the Schools of Medicine that have the FCM as a compulsory subject in the degree (3 of 27) had the highest preference for this specialty. DESIGN: Observational study on the data file of all the individuals taking the MIR examination between 2003 and 2011. LOCATION: Spain. PARTICIPANTS: All those who sat the examinations called by MIR 2003-2011. MAIN MEASUREMENTS: Position in the ranking of each candidate, elected position (specialty and center), post code of residence, sex, nationality and university in which they studied, and post code location for the residence chosen. RESULTS: The percentage electing FCM is highly correlated with the position in the ranking: 8% of graduates for the 'best' college, 46% for the worst. Very noticeable and consistent differences in the preparation for the MIR among the 27 medical schools. Ranking in the exam, female and foreigner, help predict the choice of FCM. The FCM compulsory curriculum from three universities does not seem to exert any influence. CONCLUSIONS: The convenient yardstick competition between the schools of medicine, FCM in their curriculum and the emphasis on the most attractive attributes of the specialty can contribute to the necessary renewal of FCM. PMID- 24238768 TI - Cough syncope. AB - Loss of consciousness following cough was first described in 1876 as "laryngeal vertigo" Since then, several hundred cases of what is now most commonly termed cough syncope have been reported, often in association with various medical conditions. Some early authors assumed this entity to be a form of epilepsy, but by the mid-20th century, general consensus reflected that post-tussive syncope was a consequence of markedly elevated intrathoracic pressures induced by coughing. A typical profile of the cough syncope patient emerging from the literature is that of a middle-aged, large-framed or overweight male with obstructive airways disease. Presumably, such an individual would be more likely to generate the extremely high intrathoracic pressures associated with cough induced fainting. The precise mechanism of cough syncope remains a matter of debate. Theories proposed include various consequences of the marked elevation of intrathoracic pressures induced by coughing: diminished cardiac output causing decreased systemic blood pressure and, consequently, cerebral hypoperfusion; increased cerebrospinal fluid (CSF) pressure causing increased extravascular pressure around cranial vessels, resulting in diminished brain perfusion; or, a cerebral concussion-like effect from a rapid rise in CSF pressure. More recent mechanistic studies suggest a neurally mediated reflex vasodepressor-bradycardia response to cough. Since loss of consciousness is a direct and immediate result of cough, elimination of cough will eliminate the resultant syncopal episodes. Thus, the approach to the patient with cough syncope requires thorough evaluation and treatment of potential underlying causes of cough, as summarized in several recently published cough management guidelines. PMID- 24238769 TI - Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD. AB - AIM: The administration of beta2-agonists to patients with airways obstruction often results in transient decrease in PaO2 despite concomitant bronchodilation. This effect is potentially dangerous for patients suffering from acute exacerbation of COPD (AECOPD). In this study, we investigated the effect of indacaterol 150 MUg and 300 MUg on the arterial blood gas tensions of hospitalised patients with AECOPD. METHODS: We explored the acute effects on arterial blood gases and spirometry of two doses of indacaterol Breezhaler (150 and 300 MUg) in 12 patients hospitalised because of an AECOPD in 2 non consecutive days under open-label, randomized, crossover conditions, with blind evaluation. Blood specimens were taken just before the inhalation and at 15, 30, 60, 120, 240 and 360 min after inhalation of each treatment, and spirometry was performed at the same time points. RESULTS: Both doses of indacaterol did not cause significant changes in blood gases, although some patients with relatively well-preserved PaO2 presented transient episodes of oxygen desaturation that normalize spontaneously in a very short time. Moreover, they induced a significant mean increase in FEV1 and FVC, although the improvement caused by indacaterol 300 MUg was larger. CONCLUSIONS: Indacaterol up to 300 MUg is a potent bronchodilator that may induce small, transient decrease in PaO2 mainly in patients with relatively well-preserved PaO2. There appeared to be no clinical consequences of these PaO2 abnormalities in patients suffering from AECOPD. PMID- 24238770 TI - Contrasting breathing retraining and helium-oxygen during pulmonary rehabilitation in COPD: a randomized clinical trial. AB - BACKGROUND: Breathing-retraining and helium-oxygen (heliox) have been used to improve exercise tolerance in COPD. We hypothesized that, in patients with COPD, exercise duration after exercise-training plus breathing-retraining and oxygen would be longer than after exercise-training plus heliox or after exercise training plus oxygen alone. We also explored the short-term maintenance of gains in exercise duration after using each technique. METHODS: Of 192 COPD patients recruited, 103 were randomly assigned to exercise-training plus heliox (n = 33), exercise-training plus breathing-retraining and oxygen (n = 35) and exercise training and oxygen (n = 35). FiO2 was 0.30 during testing and training in all groups. Patients exercised on a treadmill thrice-weekly for eight weeks. Before, at completion of training, and six-weeks later, patients underwent constant-load treadmill testing. RESULTS: At completion of training, improvements in exercise duration in the heliox and breathing-retraining groups were not significantly different. Compared to the exercise-training plus oxygen group, exercise duration improved more in the breathing-retraining group (P = 0.008) but not in the heliox group (P = 0.142). Hyperinflation was reduced with breathing-retraining plus oxygen compared to the other two groups. Six-weeks later, improvements in exercise duration were still greater with breathing-retraining than with exercise training (P = 0.015). In contrast, improvements in exercise duration with heliox did not differ from those in the other two groups. CONCLUSIONS: In moderate-to severe COPD, exercise-training combined with either heliox or with breathing retraining yielded not significantly different improvements in exercise duration with only the latter being superior to exercise-training. Six-weeks after training, these improvements were still greater after exercise-training plus breathing-retraining than after exercise-training. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00123422. PMID- 24238771 TI - Cleaning sprays, household help and asthma among elderly women. AB - OBJECTIVE: There is increasing evidence on the deleterious role in asthma of the use of household cleaning products in spray forms in adults. Household help might induce misclassification errors. The aim of the present analysis was to study associations between household exposure to cleaning sprays and current asthma in elderly women, taking into account household help. METHODS: A nested case-control survey on respiratory health was undertaken among a random sample of French women from the E3N study. Data were available for 570 women (235 with current asthma and 335 without asthma history; 68 years old on average, 59% never smokers). Three estimates of domestic exposure were used: 1) self-reported, 2) using principal component analysis, 3) a composite score for sprays. Associations between domestic exposures and asthma were assessed by logistic regression, adjusted for age, educational level, BMI and smoking status. Analyses were further stratified on household help in order to evaluate a potential misclassification bias. RESULTS: Among women without household help (n = 325), a significant association was observed between weekly use of at least one spray and current asthma (OR [95% CI]: 1.86[1.04-3.33]). No association was observed among women with household help. CONCLUSIONS: Weekly household use of cleaning sprays may have a deleterious effect on asthma. It is important to take into account household help to limit misclassification bias. PMID- 24238772 TI - Increased arterial stiffness in stable and severe asthma. AB - BACKGROUND: Systemic inflammation is related to disease progression in asthma. The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. The aim of this study is to evaluate the baPWV levels in patients with stable and severe asthma. METHODS: We examined baPWV, high sensitivity C-reactive protein (CRP), lung function parameters, and arterial blood gas analysis in patients with asthma and control subjects. 85 stable asthma patients and 85 severe asthmatics were investigated. 85 control subjects matched for age, gender, body mass index (BMI) and smoking status were recruited. RESULTS: The patients with severe asthma had increased baPWV and CRP compared with the patients with stable asthma and control subjects. Furthermore, baPWV was elevated in stable asthma compared with control subjects. There was a negative correlation between baPWV and forced expiratory volume in 1 s (FEV1), after adjusting age, gender, BMI and smoking status (r = -0.414, p < 0.001). Similarly, baPWV was negatively correlated with FEV1/forced vital capacity (FVC) (r = 0.431, p < 0.001). Although there was no correlation between CRP and baPWV in patients with stable asthma, CRP was positively correlated with baPWV in patients with severe asthma (r = 0.229, p = 0.039). CONCLUSIONS: baPWV tends to increase as pathogenic condition aggravated in asthma. In addition, elevated baPWV correlates with impaired lung function. Our observation suggests that baPWV is useful for early detection of subclinical atherosclerosis in asthma. PMID- 24238773 TI - Can we identify patients with different illness schema following an acute exacerbation of COPD: a cluster analysis. AB - INTRODUCTION: Pulmonary Rehabilitation (PR) reduces hospital admissions following an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) but adherence is known to be poor. Patients' illness perceptions may affect adherence to disease-management strategies but to date have not been explored following an exacerbation. The study aim is two-fold; firstly to prospectively explore acceptance and uptake of post-exacerbation PR and secondly to identify possible clusters of patients' illness perceptions following hospitalisation for an exacerbation of COPD. METHODS: Patients admitted to hospital with an exacerbation of COPD were recruited to a prospective observational study. Self-reported illness perceptions, mood, health status and self-efficacy were assessed. Acceptance and uptake of PR were recorded at six months. Cluster analysis of Illness Perceptions Questionnaire-Revised data was used to establish groups of patients holding distinct beliefs. RESULTS: 128 patients were recruited. Acceptance and uptake of PR following an acute exacerbation was poor with only 9% (n = 11) completing the programme. Cluster analysis revealed three distinct groups: Cluster 1 'in control' (n = 52), Cluster 2 'disengaged' (n = 36) and Cluster 3 'distressed' (n = 40). Significant between-cluster differences were observed in mood, health status and self-efficacy (p < 0.01). Acceptance and uptake of PR did not differ between clusters. CONCLUSIONS: Acceptance/uptake of post-exacerbation PR was found to be poor. Three distinct illness schema exist in patients following an acute exacerbation. This information may be useful in developing novel psychologically-informed interventions designed to reduce feelings of distress and perhaps facilitate a PR intervention for this vulnerable population. PMID- 24238774 TI - The gender-specific association between asthma and the need to smoke tobacco. AB - OBJECTIVES: To examine the associations between multidimensional tobacco dependence and youths' asthma status with gender as an effect modifier. BACKGROUND: Despite the adverse respiratory effects, some adolescents with asthma smoke tobacco. Girls and boys have been shown to have different motivations for tobacco use. METHODS: Secondary analyses were conducted of data obtained from 1248 adolescents who completed the British Columbia Youth Survey of Smoking and Health II. The sample was limited to youth who reported current or experimental tobacco use and who provided asthma status information. Tobacco dependence was assessed with the modified-Fagerstrom Tolerance Questionnaire and four-dimension Adolescents' Need for Smoking Scale (ANSS), which assesses social dependence, physical dependence, emotional dependence, and sensory dependence on tobacco. All analyses were stratified by gender. RESULTS: The sample was 535 boys and 713 girls who were 15.9 years of age (SD = 1.5), on average. Gender was associated with both self-reported asthma status and the physical dependence dimension of the ANSS. Multiple linear regression analyses revealed that girls with asthma, compared with girls without asthma, had higher physical tobacco dependence scores, after adjusting for demographic and other factors. None of the tobacco dependence dimensions was associated with the asthma status of boys. CONCLUSIONS: Asthmatic girls who report smoking may be doing so because they develop physical dependence relatively quickly and lose their autonomy with respect to tobacco use. They may require significant support for smoking cessation, including cognitive behavioral therapy and nicotine replacement therapy. PMID- 24238775 TI - Tissue distribution of 35S-labelled perfluorobutanesulfonic acid in adult mice following dietary exposure for 1-5 days. AB - Perfluorobutanesulfonyl fluoride (PBSF) has been introduced as a replacement for its eight-carbon homolog perfluorooctanesulfonyl fluoride (POSF) in the manufacturing of fluorochemicals. Fluorochemicals derived from PBSF may give rise to perfluorobutanesulfonic acid (PFBS) as a terminal degradation product. Although basic mammalian toxicokinetic data exist for PFBS, information on its tissue distribution has only been reported in one study focused on rat liver. Therefore, here we characterized the tissue distribution of PFBS in mice in the same manner as we earlier examined its eight-carbon homolog perfluorooctanesulfonate (PFOS) to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1, 3 or 5d to 16 mg (35)S-PFBS kg(-1) d( 1), both scintillation counting and whole-body autoradiography (WBA) revealed the presence of PFBS in all of the 20 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. After 5d of treatment the highest levels were detected in liver, gastrointestinal tract, blood, kidney, cartilage, whole bone, lungs and thyroid gland. WBA revealed relatively high levels of PFBS in male genital organs as well, with the exception of the testis. The tissue levels increased from 1 to 3 d of exposure but appeared thereafter to level-off in most cases. The estimated major body compartments were whole bone, liver, blood, skin and muscle. This exposure to PFBS resulted in 5-40-fold lower tissue levels than did similar exposure to PFOS, as well as in a different pattern of tissue distribution, including lower levels in liver and lungs relative to blood. PMID- 24238776 TI - Association of naturally occurring radionuclides in sludges from Drinking Water Treatment Plants previously optimized for their removal. AB - The raw water used in Drinking Water Treatment Plants (DWTPs) can present high values of naturally occurring radionuclides. In order to reduce this content, the routine working conditions of DWTPs were successfully modified. This meant that those radionuclides were accumulated in the sludges generated, whose radioactive content was frequently above the exemption levels. It therefore becomes necessary to assess the association of naturally occurring radionuclides in the sludges for their potential use as agricultural fertilizers. Two approaches were studied: (a) the effect of different sequential extraction methods applied to a selected sludge; and (b) the effect of the different contents of inorganic complexes dissolved in the input water on the composition of the sludges generated by two DWTPs with different origins of their input water. Uranium and radium were mainly associated with the carbonated and reducible fractions, while (210)Po and (228)Th were associated with the residual fraction. There were differences between the two speciation methods, but the order of bioavailable radionuclides was roughly the same: (226)Ra~(234,238)U>(228)Th>(210)Po. The major inorganic complexes content, mainly carbonate, in the raw water affected the radionuclide association. The greater the carbonate content in the raw water, the greater was the association of uranium and radium with the carbonated and easily reducible fractions. PMID- 24238777 TI - To harm or not to harm? On the evolution and expression of virulence in group A streptococci. AB - Group A streptococci (GAS) cause three different types of infection (sensu lato) with distinct levels of virulence: asymptomatic colonization, superficial symptomatic infection, and invasive infection. To address why this pattern with several infection types has evolved, we combine mechanistic understanding from infection medicine with recent theory from evolutionary ecology. We propose that asymptomatic colonization and superficial symptomatic infection exploit different states of the host epithelium to maximize transmission between hosts in different epidemiological conditions, whereas the ability of the bacteria to cause invasive infection is a non-adaptive side effect of traits required for superficial symptomatic infection. PMID- 24238778 TI - Treatment as prevention and cure towards global eradication of hepatitis C virus. AB - The availability of curative, direct-acting antiviral drugs against hepatitis C virus (HCV) sparks an ethical call for HCV eradication and provides essential tools to spearhead the effort. Challenges include increasing awareness of the chronic hepatitis C epidemic, garnering sufficient public, private, and governmental financial will to invest in the necessary resources, developing pangenotypic drug regimens for global application, and mitigating ethical concerns. To achieve these goals, stakeholders including clinicians, public health professionals, legislators, advocates, and industry can employ a variety of strategies such as increasing HCV screening, implementing treatment as prevention, and improving linkage to care, as well as developing innovative pricing and payment solutions, stimulating innovation through local drug development in high-prevalence regions, continuing vaccine development, and creating efficiencies in the marketing and distribution of educational materials and drug treatments. PMID- 24238779 TI - Fledgling pathoconnectomics of psychiatric disorders. AB - Pathoconnectomics, the mapping of abnormal brain networks, is a popular current framework for the study of brain dysfunction in psychiatric disorders. In this review we evaluate the conceptual foundations of this framework, describe the construction and analysis of empirical models of brain networks or connectomes, and summarize recent reports of the large-scale whole-brain connectome organization of two candidate brain-network disorders, schizophrenia and autism. We consider the evidence for the abnormal brain-network nature of psychiatric disorders and find it inconclusive. For instance, although there is some evidence for more random whole-brain network organization in schizophrenia and autism, future studies need to determine if these and other observed brain-network abnormalities represent sufficient phenotypes of psychiatric disorders, in order to validate pathoconnectomics as a scientific and clinical framework. PMID- 24238780 TI - Primate feedstock for the evolution of consonants. AB - The evolution of speech remains an elusive scientific problem. A widespread notion is that vocal learning, underlined by vocal-fold control, is a key prerequisite for speech evolution. Although present in birds and non-primate mammals, vocal learning is ostensibly absent in non-human primates. Here we argue that the main road to speech evolution has been through controlling the supralaryngeal vocal tract, for which we find evidence for evolutionary continuity within the great apes. PMID- 24238781 TI - Attachment and alcohol use amongst athletes: the mediating role of conscientiousness and alexithymia. AB - OBJECTIVE: The present study aims to explore the mediating effects of conscientiousness and alexithymia in the relationship between parental attachment style and alcohol use in a large sample of athletic young people. METHOD: Participants included 434 French sport sciences students. Alcohol use, parental attachment style, conscientiousness and alexithymia were assessed. The hypotheses were tested by using regression and bootstrapping mediation analyses. RESULTS: Maternal insecure attachment style is positively associated with alcohol use. The current study highlights a multiple pathway in this relationship. The results reveal the mediating effect of low conscientiousness and alexithymia between maternal insecure attachment and alcohol use. CONCLUSION: Athletes' alcohol use seems to be the result of a complex association of underlying psychological factors. PMID- 24238782 TI - Rate of progression from first use to dependence on cocaine or opioids: a cross substance examination of associated demographic, psychiatric, and childhood risk factors. AB - BACKGROUND: A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal. METHODS: Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD. RESULTS: In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD. CONCLUSIONS: Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances. PMID- 24238784 TI - [Impact of physical activity level on alexithymia and coping strategies in an over-40 multiple sclerosis population: a pilot study]. AB - INTRODUCTION: The aim of this study was to evaluate the impact of physical activity on alexithymia and coping strategies among people with multiple sclerosis aged over 40. The hypotheses were that physical activity should have a protective effect on alexithymia, and more particularly, on "emotional identification" and could influence coping strategies because it can be considered as a distractive coping strategy. METHODS: Thirty-seven patients aged 40 years or older were asked to complete a form including an identification sheet and standardized questionnaires: the Bermond-Vorst Alexithymia Questionnaire (version B), the Coping with Health Injuries and Problem Questionnaire, the Fatigue Impact Scale, and the Hospital Anxiety and Depression Scale. RESULTS: The participants with a high or moderate level of physical activity used "information research" as a coping strategy better than those who had a lower level of physical activity. They also analyzed their emotions better. The results revealed an association between these variables and anxiety, depression and fatigue. DISCUSSION: This study provides insight for future research about the impact of physical activity on multiple sclerosis. PMID- 24238783 TI - Brain potentials measured during a Go/NoGo task predict completion of substance abuse treatment. AB - BACKGROUND: U.S. nationwide estimates indicate that 50% to 80% of prisoners have a history of substance abuse or dependence. Tailoring substance abuse treatment to specific needs of incarcerated individuals could improve effectiveness of treating substance dependence and preventing drug abuse relapse. We tested whether pretreatment neural measures of a response inhibition (Go/NoGo) task would predict which individuals would or would not complete a 12-week cognitive behavioral substance abuse treatment program. METHODS: Adult incarcerated participants (n = 89; women n = 55) who volunteered for substance abuse treatment performed a Go/NoGo task while event-related potentials (ERPs) were recorded. Stimulus- and response-locked ERPs were compared between participants who completed (n = 68; women = 45) and discontinued (n = 21; women = 10) treatment. RESULTS: As predicted, stimulus-locked P2, response-locked error-related negativity (ERN/Ne), and response-locked error positivity (Pe), measured with windowed time-domain and principal component analysis, differed between groups. Using logistic regression and support-vector machine (i.e., pattern classifiers) models, P2 and Pe predicted treatment completion above and beyond other measures (i.e., N2, P300, ERN/Ne, age, sex, IQ, impulsivity, depression, anxiety, motivation for change, and years of drug abuse). CONCLUSIONS: Participants who discontinued treatment exhibited deficiencies in sensory gating, as indexed by smaller P2; error-monitoring, as indexed by smaller ERN/Ne; and adjusting response strategy posterror, as indexed by larger Pe. The combination of P2 and Pe reliably predicted 83.33% of individuals who discontinued treatment. These results may help in the development of individualized therapies, which could lead to more favorable, long-term outcomes. PMID- 24238785 TI - [2012 literature review on peripheral neuropathies: immune neuropathies (treatments excluded)]. AB - In 2012, interest remains high in the field of dysimmune neuropathies, chiefly concerning Guillain-Barre syndrome (GBS). The pathophysiological mechanisms are now better known but electrophysiological criteria should be updated. The risk of GBS in H1N1 vaccination is now well evaluated. Nerve ultrasonography provides new prospects for diagnosis and follow-up of dysimmune neuropathies but cannot substitute for electrophysiology. This paper aims to present some noteworthy articles published in 2012 in the field of dysimmune neuropathies. PMID- 24238786 TI - [Animal models of Charcot-Marie-Tooth disease and their relevance for understanding the disease in humans]. AB - Charcot-Marie-Tooth neuropathies (CMT) are inherited neuromuscular disorders caused by length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are responsible for Charcot-Marie-Tooth neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity renders the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodents and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. The majority of these models concern the demyelinating form (type 1) of the disease. The axonal form (type 2) is less common. Both forms can further be divided into multiple subtypes reflecting the heterogeneity of the disease. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how some of them led to clinical trials. PMID- 24238787 TI - Malnutrition in healthcare institutions: a review of the prevalence of under nutrition in hospitals and care homes since 1994 in England. AB - BACKGROUND & AIMS: One in four hospital patients in the UK are estimated to be affected by 'hospital malnutrition' (under-nutrition). There is a need for robust epidemiological data relating to the frequency, distribution and determinants of this clinical problem of public health importance. This review aims to undertake a narrative synthesis of data on the descriptive epidemiology of under-nutrition, and to address some of the methodological limitations. METHODS: A methodical review of literature was undertaken, tracking the reported prevalence and incidence of under-nutrition in hospital, in the UK, since 1994. RESULTS: The 16 articles retrieved and reviewed demonstrate that nutrition in hospital is a long standing problem in UK hospitals and care homes. The existing literature is comprised mainly of cross-sectional surveys describing the prevalence of under nutrition in hospital which ranges from 11 to 45%. There is considerable heterogeneity in the published literature on hospital malnutrition (under nutrition) and very few studies either measure or have estimated incidence. CONCLUSIONS: Under-nutrition in hospital continues to be under-addressed, yet a major public health problem in the UK. Defining the descriptive epidemiology of this problem is one of the first steps towards understanding its aetiology or planning and evaluating appropriate prevention or treatment strategies. PMID- 24238788 TI - Monosodium glutamate intake is inversely related to the risk of hyperglycemia. AB - BACKGROUND & AIMS: In animal studies, monosodium glutamate (MSG) intake at a particular age has been found to increase the risk of insulin resistance and obesity. Inconsistent associations between MSG intake and overweight have been reported in humans. No population study has assessed the association between MSG intake and diabetes risk. This study aims to prospectively examine the association between MSG intake and hyperglycemia in a Chinese population. METHODS: We followed 1056 healthy adults aged 20 years and older from 2002 to 2007. Dietary data were collected during home visits using a 3-day food record and a food frequency questionnaire. Fasting blood samples were collected at baseline and follow up. Hyperglycemia was defined as fasting plasma glucose >5.6 mmol/l. RESULTS: During the follow-up we identified 125 cases of hyperglycemia. The highest quartile of MSG intake was associated with a lower risk of incident hyperglycemia, even after adjustment for a number of covariates, including dietary patterns. Comparing the highest with the lowest quartiles of MSG intake, the odds ratio (OR) for hyperglycemia was 0.30 (95% CI 0.13-0.66). There was a linear inverse association between MSG intake and change in blood glucose. CONCLUSION: This cohort study suggests that high MSG intake is associated with a decreased risk of hyperglycemia in Chinese adults. PMID- 24238789 TI - Consumption of oral hospital diets and percent adequacy of minerals in oncology patients as an indicative for the use of oral supplements. AB - BACKGROUND & AIMS: Deficiencies in the consumption of foods and nutrients favor malnutrition in patients. Considering the recommendations for the ingestion of minerals, the content, consumption and percent adequacy of the minerals (Ca, Cu, Fe, Mg, Mn, K, P, Na, Zn and Se) were evaluated amongst oncology patients who received oral diets isolated or associated with an oral food complement (OFC), evaluating the need and composition of an oral supplement. METHODS: The mineral composition as determined by ICP-OES, and the food consumption of the patients served regular, bland and soft diets, were evaluated on six non-consecutive weekdays. Patients with increased nutritional needs received OFC. The consumptions were calculated by deducting the weight of the leftovers from the value served. RESULTS: A total of 163 patients took part of which 59.5% were men, the mean age was 57 +/- 15 years old, and 126 (77.3%), 27 (16.6%) and 10 (6.1%) were served the regular, bland and soft diets, respectively, with (23.0%), 8 (30.7%) and 4 (40.0%) receiving the OFC. Patient consumption was lower when the regular (74.2 vs 79.7%) and soft (68.9 vs 74.2%) diets were combined with OFC. For all diets, less was consumed at the lunch (61.2%-65.7%) and dinner (39.9% 62.8%) meals. Patients that received the OFC showed reduced meal consumption and higher Ca ingestion. The mineral contents of the diets were inadequate, with 66.8% of the patients ingesting Na above the UL and K below the nutritional recommendation (100%). CONCLUSION: The diet consumption, isolated or associated with OFC was insufficient, and hence the exclusion of OFC and the inclusion of a mineral supplement (without P and Na) was indicated to adequate ingestion to the nutritional recommendations. PMID- 24238790 TI - Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia. AB - BACKGROUND: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib. OBJECTIVE: The aim of this study was to estimate the cost effectiveness and the budget impact of the introduction of everolimus in Serbia in comparison to best supportive care, for mRCC patients refractory to sunitinib. METHODS: A Markov model was designed corresponding with Serbian treatment protocols. A health care payer perspective was taken, including direct costs only. Treated and untreated cohorts were followed up over 18 cycles, each cycle lasting 8 weeks, which covered the lifetime horizon of mRCC patients refractory to the first-line treatment. Annual discounted rates of 1.5% for effectiveness and 3% for costs were applied. Transitions between health states were modeled by time-dependent probabilities extracted from published Kaplan-Meier curves of PFS and overall survival (OS). Utility values were obtained from the appraisals of other mRCC treatments. One-way and probabilistic sensitivity analyses were done to test the robustness and uncertainty of the base-case estimate. Lastly, the potential impacts of everolimus on the overall health care expenditures on annual and 4-year bases were estimated in the budget-impact analysis. RESULTS: The incremental cost-effectiveness ratio for everolimus was estimated at ?86,978 per quality-adjusted life-year. Sensitivity analysis identified the hazard multiplier, a statistical approximator of OS gain, as the main driver of everolimus cost-effectiveness. Furthermore, probabilistic sensitivity analyses revealed a wide 95% CI around the base-case incremental cost-effectiveness ratio estimate (?32,594-?425,258 per quality-adjusted life-year). Finally, an average annual budgetary impact of everolimus in first 4 years after its potential reimbursement would be around ?270,000, contributing to <1% of the total budget in Serbian oncology. CONCLUSIONS: Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field. PMID- 24238791 TI - Comparison of the efficacy of Lamivudine plus adefovir versus entecavir in the treatment of Lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis. AB - BACKGROUND: Hepatitis B virus infection remains 1 of the major health threats worldwide. Currently, lamivudine plus adefovir combination therapy or entecavir monotherapy is usually used for the treatment of patients with lamivudine resistant chronic hepatitis B (CHB). However, there are few systematic comparisons between the efficacy of lamivudine plus adefovir and the efficacy of entecavir in the treatment of these patients. OBJECTIVE: The goal of this systematic study and meta-analysis was to assess the efficacy of lamivudine plus adefovir compared with entecavir for the treatment of patients with lamivudine resistant CHB. METHODS: A comprehensive literature search of PUBMED, Web of Science, WANFANG database, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Review, were screened to obtain citations from January 1990 to January 2012 in this study. Data analysis was done by using the Review Manager Software 5.1. RESULTS: Eight studies were suitable for analysis. A total of 696 patients with lamivudine-resistant CHB were studied and grouped according to treatment: 341 patients in the entecavir group and 355 patients in the lamivudine plus adefovir group. The results found that the rates of undetectable hepatitis B virus DNA levels, alanine aminotransferase normalization, hepatitis B e antigen loss, and hepatitis B e antigen seroconversion were not significantly different between the lamivudine plus adefovir group and the entecavir group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups. However, virologic breakthrough for the patients with lamivudine resistance was higher in the entecavir group than in the lamivudine plus adefovir group. CONCLUSIONS: For these CHB patients with lamivudine resistance, lamivudine plus adefovir was a better treatment option than entecavir alone. PMID- 24238792 TI - Evaluation of the effect of Naloxegol on cardiac repolarization: a randomized, placebo- and positive-controlled crossover thorough QT/QTc study in healthy volunteers. AB - BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect associated with opioid use. Naloxegol is a PEGylated derivative of naloxone in clinical development as a once-daily oral treatment of OIC. OBJECTIVES: A thorough QT/QTc study was conducted, according to International Conference on Harmonisation E14 guidelines, to characterize the effect of naloxegol on cardiac repolarization. METHODS: In this randomized, positive- and placebo-controlled crossover study, healthy men received a single dose of naloxegol 25 mg (therapeutic dose), naloxegol 150 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), or placebo in 1 of 4 sequences (Williams Latin square design). The washout time between treatment periods was at least 5 days. Digital 12-lead ECGs were recorded at baseline and at 10 time points over 24 hours after dosing in each treatment period. QT intervals were corrected for heart rate using the Fridericia formula (QTcF) and the Bazett formula (QTcB). RESULTS: A total of 52 subjects were enrolled (mean age, 28 years), and 45 received all 4 treatments. The placebo-corrected, baseline-adjusted, mean increases in QTcF with naloxegol 25 and 150 mg were both <5 msec at each time point, and all upper limits of the 2 sided 90% CI were <10 msec. Similar findings were observed using QTcB; the upper limits of the 2-sided 90% CI were <10 msec at all time points after dosing with naloxegol 25 or 150 mg. With moxifloxacin 400 mg, mean QTcF was increased by a maximum of 11.1 msec (90% CI, 9.3-12.9 msec), supporting assay sensitivity. CONCLUSION: Naloxegol at 25 and 150 mg was not associated with QT/QTc interval prolongation in these healthy men, and at the proposed therapeutic dose of 25 mg/d, naloxegol is not expected to have a clinically relevant effect on cardiac repolarization in patients with OIC. ClinicalTrials.gov identifier: NCT01325415. PMID- 24238793 TI - [A big eyelid]. PMID- 24238794 TI - Effects of shortening the dry period of dairy cows on milk production, energy balance, health, and fertility: a systematic review. AB - A dry period of 6-8 weeks for dairy cows is generally thought to maximise milk production in the next lactation. However, the value of such a long dry period is increasingly questioned. In particular, shortening the dry period shifts milk production from the critical period after calving to the weeks before calving. This shift in milk production could improve the energy balance (EB), health and fertility of dairy cows. The objective of this study was to systematically review the current knowledge on dry period length in relation to milk production, EB, fertility, and health of cows and calves. A meta-analysis was performed for variables where at least five studies were available. Overall, both shortening and omitting the dry period reduces milk production, increases milk protein percentage and tends to reduce the risk of ketosis in the next lactation. Individual studies reported an improvement of EB after a short or no dry period, compared with a conventional dry period. Shortening or omitting the dry period did not affect milk fat percentage and shortening the dry period did not alter the odds ratio for mastitis, metritis, or fertility measures in the next lactation. So, current evidence for an improvement of health and fertility of dairy cows is marginal and may be partly explained by the limited number of studies which have evaluated health and fertility in relation to dry period length, the limited number of animals in those studies and the variable responses reported. PMID- 24238797 TI - Securing poultry production from the ever-present Eimeria challenge. AB - The intestinal disease coccidiosis, caused by protozoan parasites of the genus Eimeria, is one of the most important livestock diseases in the world. It has a high impact in the poultry industry where parasite transmission is favoured by high-density housing of large numbers of susceptible birds. Coccidiosis control in poultry is achieved by careful husbandry combined with in-feed anticoccidial drugs or vaccination with live parasites. However, outbreaks of coccidiosis still occur and subclinical infections, which significantly impact on productivity and food security, are common due to widespread drug resistance, high parasite prevalence, and environmental persistence. Herein, we review some recent approaches for the production of cheaper third generation vaccines, based on robust methods for identification of immunoprotective antigens and the use of transgenic Eimeria. PMID- 24238796 TI - Functional connectomics from resting-state fMRI. AB - Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI (rfMRI) for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image-processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project and highlight some upcoming challenges in functional connectomics. PMID- 24238798 TI - Recycling of air pollution control residues from municipal solid waste incineration into lightweight aggregates. AB - This work focuses on the assessment of technological properties and on the leaching behavior of lightweight aggregates (LWA) produced by incorporating different quantities of air pollution control (APC) residues from municipal solid waste (MSW) incineration. Currently this hazardous waste has been mostly landfilled after stabilization/solidification. The LWA were produced by pelletizing natural clay, APC residues as-received from incineration plant, or after a washing treatment, a small amount of oil and water. The pellets were fired in a laboratory chamber furnace over calcium carbonate. The main technological properties of the LWA were evaluated, mainly concerning morphology, bulk and particle densities, compressive strength, bloating index, water adsorption and porosity. Given that APC residues do not own expansive (bloating) properties, the incorporation into LWA is only possible in moderate quantities, such as 3% as received or 5% after pre-washing treatment. The leaching behavior of heavy metals from sintered LWA using water or acid solutions was investigated, and despite the low acid neutralization capacity of the synthetic aggregates, the released quantities were low over a wide pH range. In conclusion, after a washing pre-treatment and if the percentage of incorporation is low, these residues may be incorporated into LWA. However, the recycling of APC residues from MSW incineration into LWA does not revealed any technical advantage. PMID- 24238799 TI - Anaerobic digestion of autoclaved and untreated food waste. AB - Anaerobic digestion of autoclaved (160 degrees C, 6.2 bar) and untreated source segregated food waste (FW) was compared over 473 days in semi-continuously fed mesophilic reactors with trace elements supplementation, at organic loading rates (OLRs) of 2, 3, 4 and 6 kg volatile solids(VS)/m(3)d. Methane yields at all OLR were 5-10% higher for untreated FW (maximum 0.483+/-0.013 m(3) CH4/kg VS at 3 kg VS/m(3) d) than autoclaved FW (maximum 0.439+/-0.020 m(3) CH4/kg VS at 4 kg VS/m(3) d). The residual methane potential of both digestates at all OLRs was less than 0.110 m(3) CH4/kg VS, indicating efficient methanation in all cases. Use of acclimated inoculum allowed very rapid increases in OLR. Reactors fed on autoclaved FW showed lower ammonium and hydrogen sulphide concentrations, probably due to reduced protein hydrolysis as a result of formation of Maillard compounds. In the current study this reduced biodegradability appears to outweigh any benefit due to thermal hydrolysis of ligno-cellulosic components. PMID- 24238800 TI - Environmental burdens in the management of end-of-life cathode ray tubes. AB - We compared the environmental burdens in the management of end-of life cathode ray tubes (CRTs) within two frameworks according to the different technologies of the production of televisions/monitors. In the first case, CRT recycling is addressed to the recovery of the panel and funnel glass for the manufacturing of new CRT screens. In the second case, where flat screen technology has replaced that of CRT, the recycling is addressed to the recovery of the glass cullet and lead for other applications. The impacts were evaluated according to the problem oriented methodology of the Institute of Environmental Sciences, Leiden University, Leiden, The Netherlands. Our data confirm that in both cases, the recycling treatment allows benefits to be gained for the environment through the recovery of the secondary raw materials. These benefits are higher for the "CRT technology" framework (1 kg CO2 saved per CRT) than for the "flat screen technology" (0.9 kg CO2 saved, per CRT, as the highest possible), mainly due to the high energy consumption for lead separation from the funnel glass. Furthermore, the recovery of yttrium from the fluorescent powders that are a residue of the recycling treatment would further improve the CO2 credit for both the frameworks considered, which would provide a further saving of about 0.75 kg CO2 per CRT, net of the energy and raw materials needed for the recovery. Overall, this study confirms that, even with a change in the destination of the recovered materials, the recycling processes provide a benefit for the environment: indeed the higher loads for the environment are balanced by avoiding the primary production of the recovered materials. PMID- 24238801 TI - Effects of thermobarical pretreatment of cattle waste as feedstock for anaerobic digestion. AB - Lab-scale experiments were conducted to assess the impact of thermobarical treatment of cattle waste on anaerobic digestion. Treatment was at temperatures of 140-220 degrees C in 20K steps for a 5-min duration. Methane yields could be increased by up to 58% at a treatment temperature of 180 degrees C. At 220 degrees C the abundance of inhibitors and other non-digestible substances led to lower methane yields than those obtained from untreated material. In an extended analysis it could be demonstrated that there is a functional correlation between the methane yields after 30 days and the formation rate and methane yield in the acceleration phase. It could be proved in a regression of these correlation values that the optimum treatment temperature is 164 degrees C and that the minimum treatment temperature should be above 115 degrees C. PMID- 24238802 TI - Solid waste bin detection and classification using Dynamic Time Warping and MLP classifier. AB - The increasing requirement for Solid Waste Management (SWM) has become a significant challenge for municipal authorities. A number of integrated systems and methods have introduced to overcome this challenge. Many researchers have aimed to develop an ideal SWM system, including approaches involving software based routing, Geographic Information Systems (GIS), Radio-frequency Identification (RFID), or sensor intelligent bins. Image processing solutions for the Solid Waste (SW) collection have also been developed; however, during capturing the bin image, it is challenging to position the camera for getting a bin area centralized image. As yet, there is no ideal system which can correctly estimate the amount of SW. This paper briefly discusses an efficient image processing solution to overcome these problems. Dynamic Time Warping (DTW) was used for detecting and cropping the bin area and Gabor wavelet (GW) was introduced for feature extraction of the waste bin image. Image features were used to train the classifier. A Multi-Layer Perceptron (MLP) classifier was used to classify the waste bin level and estimate the amount of waste inside the bin. The area under the Receiver Operating Characteristic (ROC) curves was used to statistically evaluate classifier performance. The results of this developed system are comparable to previous image processing based system. The system demonstration using DTW with GW for feature extraction and an MLP classifier led to promising results with respect to the accuracy of waste level estimation (98.50%). The application can be used to optimize the routing of waste collection based on the estimated bin level. PMID- 24238803 TI - [Pneumonia Severity Index in the emergency department and the use of a short-stay unit to improve outcome indicators in community-acquired pneumonia]. PMID- 24238804 TI - A study of acoustic source generation mechanism of Magnetoacoustic Tomography. AB - Magnetoacoustic Tomography (MAT) is a non-invasive imaging modality for electrical conductivity with good contrast and high spatial resolution. We have analyzed the acoustic source generation mechanism of MAT and presented its physical model, including the simulations and experiments in this paper. In MAT, acoustic sources are generated in a conductive object placed in a static magnetic field. Pulsed current is injected into the object and produces a Lorentz force due to the static magnetic filed. Acoustic vibration was excited by the Lorentz force, and hence, ultrasound waves propagate in all directions and are collected with transducers placed around the object. The conductivity image can then be reconstructed with acoustic waves using some reconstruction algorithms. Because the acoustic source generation mechanism of MAT is the key problem of forward and inverse problems, we analyzed the physical process of acoustic source generation and presented the acoustic dipole source model according to the Lorentz force imposed on the object. In addition, computer simulations and experiments were also conducted. The results of simulations applying an acoustic dipole source model are consistent with experimental results. This study has cardinal significance for the accurate algorithm of MAT and provides a methodology and reference for acoustic source problems. PMID- 24238805 TI - Development of laryngeal video stroboscope with laser marking module for dynamic glottis measurement. AB - Physicians clinically use laryngeal video stroboscope as an auxiliary instrument to test glottal diseases, and read vocal fold images and voice quality for diagnosis. As the position of vocal fold varies in each person, the proportion of the vocal fold size as presented in the vocal fold image is different, making it impossible to directly estimate relevant glottis physiological parameters, such as the length, area, perimeter, and opening angle of the glottis. Hence, this study designs an innovative laser projection marking module for the laryngeal video stroboscope to provide reference parameters for image scaling conversion. This innovative laser projection marking module to be installed on the laryngeal video stroboscope using laser beams to project onto the glottis plane, in order to provide reference parameters for scaling conversion of images of laryngeal video stroboscope. PMID- 24238807 TI - Synthesis, characterization, antimicrobial activity and applications of polyanilineTi(IV)arsenophosphate adsorbent for the analysis of organic and inorganic pollutants. AB - A novel polyaniline based composite cation exchange material has been synthesized by simple chemical route and characterized on the basis of sophisticated techniques. XRD and SEM analyses reveal the amorphous morphology of the material. The partition coefficient studies of different metal ions on the material were performed in DMW and diverse concentrations of HClO4 solutions. On the basis of high Kd values some significant separations of heavy toxic metal ions were achieved from synthetic mixtures as well as tap water samples by using columns of this exchanger. For the optimum adsorption of dye on the material, the effect of various parameters along with Langmuir and Freundlich adsorption isotherm were examined. The observed result of conducting measurement indicates that the material covers semiconductor range. The photochemical degradation of industrial dyes and antimicrobial activity were also investigated which show significant results than some of the known antibiotics. On the basis of good ion exchange capacity along with photochemical degradation and microbial activity, polyanilineTi(IV)arsenophosphate can be considered as an excellent conducting material for the treatment metal ions and degradation of organic pollutants. PMID- 24238806 TI - Ion exchange membrane bioreactor for treating groundwater contaminated with high perchlorate concentrations. AB - Perchlorate contamination of groundwater is a worldwide concern. The most cost efficient treatment for high concentrations is biological treatment. In order to improve and increase the acceptance of this treatment, there is a need to reduce the contact between micro organisms in the treatment unit and the final effluent. An ion exchange membrane bioreactor (IEMB), in which treated water is separated from the bioreactor, was suggested for this purpose. In this study, the IEMB's performance was studied at a concentration as high as 250mgL(-1) that were never studied before. In the bioreactor, glycerol was used as a low cost and nontoxic carbon and energy source for the reduction of perchlorate to chloride. We found that high perchlorate concentrations in the feed rendered the anion exchange membrane significantly less permeable to perchlorate. However, the presence of bacteria in the bio-compartment significantly increased the flux through the membrane by more than 25% in comparison to pure Donnan dialysis. In addition, the results suggested minimal secondary contamination (<3mgCL(-1)) of the treated water with the optimum feed of carbon substrate. Our results show that IEMB can efficiently treat groundwater contaminated with perchlorate as high as 250mgL( 1). PMID- 24238808 TI - Fluorescence detection of trace TNT by novel cross-linking electropolymerized films both in vapor and aqueous medium. AB - Electropolymerized (EP) films with high fluorescent efficiency are introduced to the detection of trace 2,4,6-trinitrotoluene (TNT). Three electroactive materials TCPC, OCPC and OCz have been synthesized and their EP films have been demonstrated to be sensitive to TNT. Among them, the TCPC EP films have displayed the highest sensitivity to TNT in both vapor and aqueous medium, even in the natural water. It is proposed that the good performances would be caused by the following two factors: first, the cross-linking network of EP films can generate the cavities which benefit the TNT penetration, and remarkably increase the contact area between the EP films and TNT; second, the frontier orbits distribution leads the fast photo-induced electron transfer (PET) from the TCPC EP films to TNT. Our results prove that these EP films are promising TNT sensing candidates and provide a new method to prepare fluorescent porous films. PMID- 24238809 TI - Synthesis, characterization and stability of Cr(III) and Fe(III) hydroxides. AB - Chromium is a common contaminant of soils and aquifers and constitutes a major environmental problem. In nature, chromium usually exists in the form of two oxidation states, trivalent, Cr(III), which is relatively innocuous for biota and for the aquatic environment, and hexavalent, Cr(VI) which is toxic, carcinogenic and very soluble. Accordingly, the majority of wastewater and groundwater treatment technologies, include a stage where Cr(VI) is reduced to Cr(III), in order to remove chromium from the aqueous phase and bind the element in the form of environmentally stable solid compounds. In the absence of iron the final product is typically of the form Cr(OH)3.xH2O whereas in the presence of iron the precipitate is a mixed Fe(1-x)Crx(OH)3 phase. In this study, we report on the synthesis, characterisation and stability of mixed (Fex,Cr1-x)(OH)3 hydroxides as compared to the stability of Cr(OH)3. We established that the plain Cr(III) hydroxide, abiding to the approximate molecular formula Cr(OH)3.3H2O, was crystalline, highly soluble, i.e. unstable, with a tendency to transform into the stable amorphous hydroxide Cr(OH)3(am) phase. Mixed Fe0.75Cr0.25(OH)3 hydroxides were found to be of the ferrihydrite structure, Fe(OH)3, and we correlated their solubility to that of a solid solution formed by plain ferrihydrite and the amorphous Cr(III) hydroxide. Both our experimental results and thermodynamic calculations indicated that mixed Fe(III)-Cr(III) hydroxides are more effective enhancers of groundwater quality, in comparison to the plain amorphous or crystalline Cr(III) hydroxides, the latter found to have a solubility typically higher than 50MUg/l (maximum EU permitted Cr level in drinking water), while the amorphous Cr(OH)3(am) phase was within the drinking water threshold in the range 5.7= 110 degrees . No radiographic parameters were associated with the development of PCC. PMID- 24238825 TI - Topical administration of tranexamic acid in primary total hip and total knee arthroplasty. AB - Major blood loss is a known potential complication in total hip and total knee arthroplasty. We conducted a prospective, stratified, randomized, double-blind, placebo-controlled trial that evaluated 100 patients undergoing total knee or total hip arthroplasty to evaluate the effect on blood loss using the topical application of tranexamic acid. Participants received either 2 g of topical tranexamic acid or the equivalent volume of placebo into the joint prior to surgical closure. Tranexamic acid resulted in a lower mean maximum decline in postoperative hemoglobin levels when compared to placebo (P = 0.013). Patients in the tranexamic acid group demonstrated an improved but non-significant reduction in the units of blood transfused compared to placebo (P = 0.423). There was no clinically significant increase in complications in the tranexamic acid group, including no incidence of venous thromboembolism. PMID- 24238826 TI - Molecular characterization of weaker variants of A and B in Indian population- the first report. AB - BACKGROUND AND OBJECTIVES: The ABO blood group system is extremely important blood group system in transfusion medicine and weaker variants of A and B are subgroups of the system. From a Country like India with 1.2 billion population sporadic reports detecting weaker variants of A and B serologically are published. Therefore the main objective of the present study is to identify weaker variants of A and B serologically and characterize them at molecular level. MATERIALS AND METHODS: Eight samples which were referred to us for resolving discrepancies in forward and reverse grouping were first phenotype in our laboratory by standard serologic techniques for ABO blood groups. Molecular genotyping for the ABO locus was done by PCR-SSCP. Altered SSCP patterns were analysed by DNA sequencing. Sequencing of intron 6 and exons 1-5 was done in one sample each. RESULTS AND CONCLUSION: Nine rare alleles affecting the normal expression of A and B antigens have been identified among Indians. They were two Aw06, one A209, one Ax20, two O05, one O49, one O56 and one O19 alleles. This is the first report demonstrating molecular studies on weaker variants of A and B from India. PMID- 24238827 TI - Effects of Ureaplasma parvum lipoprotein multiple-banded antigen on pregnancy outcome in mice. AB - Ureaplasma spp. are members of the family Mycoplasmataceae and have been considered to be associated with chorioamnionitis and preterm delivery. However, it is unclear whether Ureaplasma spp. have virulence factors related to these manifestations. The purpose of the present study was to determine whether the immunogenic protein multiple-banded antigen (MBA) from Ureaplasma parvum is a virulence factor for preterm delivery. We partially purified MBA from a type strain and clinical isolates of U. parvum, and also synthesized a diacylated lipopeptide derived from U. parvum, UPM-1. Using luciferase assays, both MBA-rich fraction MRF and UPM-1 activated the NF-kappaB pathway via TLR2. UPM-1 upregulated IL-1beta, IL-6, IL-12p35, TNF-alpha, MIP2, LIX, and iNOS in mouse peritoneal macrophage. MRF or UPM-1 was injected into uteri on day 15 of gestation on pregnant C3H/HeN mice. The intrauterine MRF injection group had a significantly higher incidence of intrauterine fetal death (IUFD; 38.5%) than the control group (14.0%). Interestingly, intrauterine injection of UPM-1 caused preterm deliveries at high concentration (80.0%). In contrast, a low concentration of UPM-1 induced a significantly higher rate of fetal deaths (55.2%) than the control group (14.0%). The placentas of the UPM-1 injection group showed neutrophil infiltration and increased iNOS protein expression. Our data indicate that MBA from the clinical isolate of U. parvum is a potential virulence factor for IUFD and preterm delivery in mice and that the N-terminal diacylated lipopeptide is essential for the initiation of inflammation. PMID- 24238828 TI - Endoscopy-assisted posterior lumbar interbody fusion in a single segment. AB - Posterior lumbar interbody fusion (PLIF) has been routinely performed for the treatment of lumbar segmental lesions. However, traditional PLIF procedures can result in a variety of approach-related morbidities. The purpose of this study was to determine the efficacy of endoscopy-assisted PLIF in lumbar arthrodesis. From July 2005 to May 2007, a total of 56 patients underwent PLIF, including 24 endoscopy-assisted operations (endoscopic group) and 32 traditional open operations (open group). The perioperative data, clinical outcomes and radiographic results were compared. The intraoperative bleeding volume, postoperative drainage volume, intraoperative and postoperative allogeneic blood transfusion volumes, values for C-reactive protein and erythrocyte sedimentation rate on postoperative day 3 and postoperative hospitalization days were decreased in the endoscopic group (p<0.05), while the operative time was longer than that of the open group (p=0.026). According to the Visual Analog Scale for pain, the postoperative low back pain score in the endoscopic group was lower than that observed in the open group (p<0.05). In the endoscopic group, the excellent and good outcome rate was 87.5%, the incidence of complications was 8.3%, and the intervertebral fusion rate was 100%. There were no significant differences for these outcomes when compared with the open group (p>0.05). Endoscopy-assisted PLIF can achieve a clinical efficacy similar to that of traditional open operations while minimizing destruction to adjacent tissues. This technique is safe and is characterized by less bleeding, less tissue trauma, decreased postoperative pain, rapid recovery, and a shorter postoperative hospital stay. PMID- 24238829 TI - Azo dyes and the blood-brain barrier: Robert Aird's novel concept in chronic neurological disease (1903-2000). AB - The well-established medical involvement of derivatives of the azo dye industry lent credibility to the 1935 announcement by Stanley Cobb of the use of vital brilliant red dye as an anticonvulsant. Although in the fullness of time clinical experience would discard this concept, nevertheless it was to give rise to Robert Aird who posited that the mechanism of action of this dye was due to its ability to decrease the permeability of the blood-brain barrier. In a very prolonged exploration of this concept, Aird concluded that blood-brain barrier permeability underlay the causation of a long list of chronic neurological conditions--a concept that was eventually abandoned. This article examines the details and the effects of this concept and its impact upon neurology. PMID- 24238830 TI - Levetiracetam following liver and kidney failure in late-onset anticonvulsant hypersensitivity syndrome. AB - Anticonvulsant hypersensitivity syndrome is an adverse drug reaction usually occurring from 1 to 8 weeks after exposure to antiepileptic drugs. It can threaten life by affecting the liver, kidneys, central nervous system or lungs. We present a 47-year-old patient treated with phenytoin, lamotrigine and clobazam for 7 years. He presented with hepatic and renal failure in relation to this syndrome demonstrated by renal biopsy. Prognosis was excellent due to an early diagnosis leading to cessation of the causative agents. Levetiracetam was started with a good response. PMID- 24238831 TI - Cell polarity signaling. AB - Cell polarity is a fundamental entity of living organisms. Cells must receive accurate decisions where to divide and along which plane, along which axis to grow, where to grow structures like flagellum or filopodium and how to differentially respond to external stimuli. In multicellular organisms cell polarity also regulates cell-cell communication, pattern formation and cell identity. In eukaryotes the RHO family of small G proteins have emerged as central regulators of cell polarity signaling. It is by now well established that ROPs, the plant specific RHO subfamily members, affect cell polarization. Work carried out over the last several years is beginning to reveal how ROPs are activated, how their activity is spatially regulated, through which effectors they regulate cell polarity and how they interact with hormonal signaling and other polarity determinants. The emerging picture is that while the mechanisms of cell polarity signaling are often unique to plants, the principles that govern cell polarization signaling can be similar. In this review, we provide an updated view of polarity signaling in plants, primarily focusing on the function of ROPs and how they interact with and coordinate different polarity determinants. PMID- 24238832 TI - Prophylactic broad spectrum antibiotics as a new anti-myeloma therapy. AB - Multiple myeloma is a common, yet incurable, haematological neoplasm. The reciprocal communication between malignant plasma cells, other cell types, and the extracellular matrix in the bone marrow micro-eco system is mediated by cell cell and cell-matrix adhesion, as well as the production of different soluble factors, and is crucial for tumour growth and drug resistance. Inflammation and pro-inflammatory cytokines contribute to the clonal expansion of neoplastic plasmacytes. This extremely complex pathogenesis of multiple myeloma gives us the opportunity to promote numerous novel drugs and approaches based on the paradigm of targeted therapy. Immune dysfunction is a hallmark of multiple myeloma. Intrinsic and therapy-related immunosuppression leads to an increased risk of recurrent infection, the major cause of mortality. However, little data is available regarding the possible influence of infection on the biology and progression of multiple myeloma. Some authors have shown that pathogenic microorganisms can activate tool-like receptors on myeloma cells, as well as the robust production of pro-inflammatory cytokines; together these factors can contribute to myeloma growth, survival, and progression. Therefore, we proposed a simple, inexpensive, and new approach for anti-myeloma therapy that, to the best of our knowledge, is the first one concerning the prophylactic, long-term use of broad-spectrum antibiotics during the course of disease regardless of the chosen concomitant regimens. Prophylactic treatment with antibiotics should suppress the pro-inflammatory milieu produced during recurrent bacterial infections and prevent the activation of tool-like receptors on tumour cells, which are important factors responsible for tumour growth and survival in patients with multiple myeloma. PMID- 24238833 TI - Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects. AB - In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance. PMID- 24238834 TI - In vivo evaluation of the HeartWare MVAD Pump. AB - OBJECTIVE: The current design trend for left ventricular assist devices (LVADs) is miniaturization, which aims to increase the treatable patient population and enable new treatment indications by reducing surgical trauma and the complications associated with device implantation. The MVAD Pump (HeartWare Inc, Framingham, MA) is a small, axial VAD that uses magnetic and hydrodynamic impeller technology and incorporates wide helical flow channels to minimize shear stress. In this study, we implanted the MVAD Pump in an ovine model to evaluate device hemocomaptiblity, biocompatibility, performance, and safety. METHODS: The MVAD Pump was implanted in an ovine model (n = 9) for 90 days. The pump was implanted through a thoracotomy and secured to the LV apex with a gimbaled sewing ring, which allowed for intraoperative adjustment of the insertion depth and angle of the inflow cannula. Serum analytes and coagulation parameters were analyzed at specific intervals throughout the study period. Pump flow, speed, and power were recorded daily to monitor device performance. Sheep were electively euthanized at 90 days for pathologic and histologic analysis. RESULTS: In this study, results demonstrated the safety, reliability, hemocompatability, and biocompatibility of the MVAD Pump. Nine animals were implanted for 90 +/- 5 days. No complications occurred during surgical implantation. Seven of the 9 animals survived until elective sacrifice. Each sheep that survived to the scheduled explant appeared physically normal, with no signs of cardiovascular or other organ compromise. The 2 sheep that were euthanized early showed no evidence of device-related issues. CONCLUSIONS: The MVAD Pump was successfully implanted through a thoracotomy and demonstrated excellent hemodynamic support with no device malfunctions throughout the study period. PMID- 24238835 TI - [Epidemiology of cerebrovascular disease in Spain]. AB - In Spain, cerebrovascular disease (CVD) is a very common cause of morbidity and hospitalization. They are the second leading cause of mortality in the general population, and the first in women. They also constitute a very high social spending, which is estimated to increase in coming years, due to the aging of our population. Data from the Hospital Morbidity Survey of the National Statistics Institute recorded, in 2011, 116,017 strokes and 14,933 transient ischemic attacks, corresponding, respectively, to an incidence of 252 and 32 events per 100,000 people. In 2002, the cost of hospitalization for each stroke was estimated at ?3,047. The amount of total cost health care throughout the life of a stroke patient is calculated at ?43,129. Internationally, the direct costs of stroke constitute 3% of national health spending, this being similar amount in different countries around us. Hypertension was the cardiovascular risk factor (CVRF) more prevalent in both ischemic and hemorrhagic strokes, followed by dyslipidemia and diabetes mellitus. Peripheral arterial disease and hypertension were more frequently associated with atherothrombotic events, atrial fibrillation with cardioembolic strokes, and obesity and high blood pressure to lacunar infarcts. In Spain, as showing several studies, we are far from optimal control of CVRF, especially in secondary prevention of stroke. According to the ICTUSCARE study, achieving recommended values was 17.6% in the case of hypertension, 29.8% in LDL-cholesterol, 74.9% of smoking, and 50.2% in diabetes mellitus. In this review, we analyze in detail the epidemiology, prevention and costs originated by CVD. PMID- 24238836 TI - [Aortic aneurysm]. AB - Aortic aneurysm is one important cause of death in our country. The prevalence of abdominal aortic aneurism (AAA) is around 5% for men older than 50 years of age. Some factors are associated with increased risk for AAA: age, hypertension, hypercholesterolemia, cardiovascular disease and, in particular, smoking. The medical management of patients with an AAA includes cardiovascular risk treatment, particularly smoking cessation. Most of major societies guidelines recommend ultrasonography screening for AAA in men aged 65 to 75 years who have ever smoked because it leads to decreased AAA-specific mortality. PMID- 24238837 TI - Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy. AB - To determine if the presence of bilateral implants, in addition to other anatomic and treatment-related variables, affects coverage of the target volume and dose to the heart and lung in patients receiving postmastectomy radiation therapy (PMRT). A total of 197 consecutive women with breast cancer underwent mastectomy and immediate tissue expander (TE) placement, with or without exchange for a permanent implant (PI) before radiation therapy at our center. PMRT was delivered with 2 tangential beams + supraclavicular lymph node field (50Gy). Patients were grouped by implant number: 51% unilateral (100) and 49% bilateral (97). The planning target volume (PTV) (defined as implant + chest wall + nodes), heart, and ipsilateral lung were contoured and the following parameters were abstracted from dose-volume histogram (DVH) data: PTV D95% > 98%, Lung V20Gy > 30%, and Heart V25Gy > 5%. Univariate (UVA) and multivariate analyses (MVA) were performed to determine the association of variables with these parameters. The 2 groups were well balanced for implant type and volume, internal mammary node (IMN) treatment, and laterality. In the entire cohort, 90% had PTV D95% > 98%, indicating excellent coverage of the chest wall. Of the patients, 27% had high lung doses (V20Gy > 30%) and 16% had high heart doses (V25Gy > 5%). No significant factors were associated with suboptimal PTV coverage. On MVA, IMN treatment was found to be highly associated with high lung and heart doses (both p < 0.0001), but implant number was not (p = 0.54). In patients with bilateral implants, IMN treatment was the only predictor of dose to the contralateral implant (p = 0.001). In conclusion, bilateral implants do not compromise coverage of the target volume or increase lung and heart dose in patients receiving PMRT. The most important predictor of high lung and heart doses in patients with implant-based reconstruction, whether unilateral or bilateral, is treatment of the IMNs. Refinement of radiation techniques in reconstructed patients who require comprehensive nodal irradiation is warranted. PMID- 24238838 TI - Pu(V) transport through Savannah River Site soils - an evaluation of a conceptual model of surface- mediated reduction to Pu (IV). AB - Over the last fifteen years the Savannah River Site (SRS) in South Carolina, USA, was selected as the site of three new plutonium facilities: the Mixed Oxide Fuel Fabrication Facility, Pit Disassembly and Conversion Facility, and the Pu Immobilization Plant. In order to assess the potential human and environmental risk associated with these recent initiatives, improved understanding of the fate and transport of Pu in the SRS subsurface environment is necessary. The hypothesis of this study was that the more mobile forms of Pu, Pu(V) and Pu(VI), would be reduced to the less mobile Pu(III/IV) oxidation states under ambient SRS subsurface conditions. Laboratory-scale dynamic flow experiments (i.e., column studies) indicated that Pu(V) was very mobile in SRS sediments. At higher pH values the mobility of Pu decreased and the fraction of Pu that became irreversibly sorbed to the sediment increased, albeit, only slightly. Conversely, these column experiments showed that Pu(IV) was essentially immobile and was largely irreversibly sorbed to the sediment. More than 100 batch sorption experiments were also conducted with four end-member sediments, i.e., sediments that include the chemical, textural, and mineralogical properties likely to exist in the SRS. These tests were conducted as a function of initial Pu oxidation state, pH, and contact time and consistently demonstrated that although Pu(V) sorbed initially quite weakly to sediments, it slowly, over the course of <33 days, sorbed very strongly to sediments, to approximately the same degree as Pu(IV). This is consistent with our hypothesis that Pu(V) is reduced to the more strongly sorbing form of Pu, Pu(IV). These studies provide important experimental support for a conceptual geochemical model for dissolved Pu in a highly weathered subsurface environment. That is that, irrespective of the initial oxidation state of the dissolved Pu introduced into a SRS sediment system, Pu(IV) controls the environmental transport within a couple weeks and Pu strongly binds to the sediment, limiting its mobility. PMID- 24238839 TI - Simultaneous detection of the feline lungworms Troglostrongylus brevior and Aelurostrongylus abstrusus by a newly developed duplex-PCR. AB - In addition to Aelurostrongylus abstrusus (Strongylida: Angiostrongylidae), referred to as the feline lungworm, Troglostrongylus brevior (Strongylida: Crenosomatidae) has recently been identified as an agent of bronco-pulmonary infestations in cats. These two parasites have a similar biology, share ecological niches, potentially co-infesting cats, but are difficult to be differentiated due to the morphological similarities of their first-stage larvae (L1). This paper describes a molecular tool, based on single-step duplex polymerase chain reaction (duplex-PCR) on the ribosomal internal transcribed spacer 2 region (ITS-2) for the simultaneous detection and differentiation of T. brevior and A. abstrusus. L1 of both species were collected from faecal samples, morphologically identified, and single larval specimens isolated. An aliquot of faeces was used as a test sample for a case of mixed natural infestation. The duplex-PCR was performed using species-specific forward primer sets for the ITS-2 region (i.e., A. abstrusus: 220bp; T. brevior: 370bp). The detection limit of the molecular assay was also assessed by serial dilutions of DNA from single larvae of both species (from ~ 4.0 to 4.0 * 10(-5) MUg/MUl). The duplex-PCR carried out on individual DNA samples was able to detect as low as 5.2 * 10(-3) MUg/MUl of DNA for A. abstrusus, 4.9 * 10(-3)MUg/MUl for T. brevior, and as low as 4.0 * 10( 3) MUg/MUl for samples containing both species. Species-specific bands of the expected sizes and two bands were simultaneously amplified from the faecal sample containing both species. The phylogenetic analyses of the ITS-2 sequences here examined and those available for other metastrongyloids were concordant in clustering them with those of other Troglostrongylus brevior and A. abstrusus sequences available in GenBank database. This molecular approach proved to be effective and highly sensitive for the simultaneous detection of the two lungworms species and it might be used for molecular epidemiological studies and for monitoring therapeutic protocols. PMID- 24238840 TI - Diffusion weighted MR imaging and proton MR spectroscopy findings of central neurocytoma with pathological correlation. AB - PURPOSE: Three cases of histopathologically confirmed central neurocytoma (CN) are presented, emphasizing diagnostic imaging issues: conventional magnetic resonance imaging with Proton magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) findings of CN. MATERIALS AND METHODS: Patients age ranged from 17 to 32 years, Imaging include a CT scan and MR examination with DWI and proton MRS on a 1.5-T system. DWI and subsequent apparent diffusion coefficient (ADC) were obtained in all. Single voxel MRS was performed prior to surgery using a point resolved spectroscopy sequence (PRESS) with short 35 ms and long echotime (TE) 144 ms, associated with a two-dimensional chemical Shift Imaging (2D-CSI) with 144 ms TE (one case). Histopathological examination included immunostaining with synaptophysin. RESULTS: With the long TE, a variable amount of glycine with markedly increased choline, very small to almost complete loss of N acetylaspartate and creatine, and inverted triplet of alanine-lactate were observed in all three patients. Increased glutamate and glutamine complex (Glx) was also observed in all with short TE. DWI demonstrated variable low ADC which appeared well correlated with the tumor signal intensity and cell density: the most homogeneous and highly dense cellular tumor with increased nucleus to cytoplasm ratio demonstrated the lower ADC. Histological pattern was typical in two cases and demonstrated an oligodendroglioma-like pattern in one case. Positivity for synaptophysin confirmed the neuronal origin in all. CONCLUSION: The demonstration within an intraventricular tumor of both glycine and alanine on MRS along with high choline, bulky Glx and restricted diffusion appear diagnostic of CN. PMID- 24238841 TI - Association of elevated plasma viscosity with small vessel occlusion in ischemic cerebral disease. AB - INTRODUCTION: Elevated plasma viscosity (PV) is observed in patients with vascular risk factors, such as diabetes mellitus or arterial hypertension. In this study we investigated the association of plasma viscosity and the different clinical and radiological entities of cerebral ischemia. METHODS: PV of 465 consecutively admitted patients with clinical symptoms of acute cerebral ischemia without radiological signs of bleeding was measured. Data is expressed as median [range] unless stated otherwise. p<0.05 was considered statistically significant. RESULTS: Patients with acute cerebral ischemia (TIA or Stroke) showed increased PV (TIA 1.27mPas [1.07-1.53], stroke 1.27mPas [1.07-1.56]) compared to patients without cerebral ischemia (Mimics) (1.23mPas [1.06-1.42]). The group with radiologically proven small vessel disease (SVD) had a significantly higher mean values of PV (1.29mPas [1.06-1.54]) compared to those with signs of large vessel disease or cardioembolic events (1.22mPas [1.07-1.56], p<0.001). Patients with chronic heart failure (p=0.007), arterial hypertension (p<0.001) and diabetes mellitus (p=0.002) had higher PV compared to patients without these cardiovascular risk factors. Hyperlipidemia or nicotine abuse showed no relation to PV. CONCLUSION: Elevated PV is not only associated TIA and Stroke but is also found in patients with radiological signs of cerebral SVD. High levels of PV could be an underestimated risk for TIA and Stroke and participate in the complex pathophysiology of SVD. Prospective observational and interventional studies are warranted for further evaluation of PV in neurological ischemic diseases. PMID- 24238842 TI - ADHD and relative risk of accidents in road traffic: a meta-analysis. AB - The present meta-analysis is based on 16 studies comprising 32 results. These studies provide sufficient data to estimate relative accident risks of drivers with ADHD. The overall estimate of relative risk for drivers with ADHD is 1.36 (95% CI: 1.18; 1.57) without control for exposure, 1.29 (1.12; 1.49) when correcting for publication bias, and 1.23 (1.04; 1.46) when controlling for exposure. A relative risk (RR) of 1.23 is exactly the same as found for drivers with cardiovascular diseases. The long-lasting assertion that "ADHD-drivers have an almost fourfold risk of accident compared to non-ADHD-drivers", which originated from Barkley et al.'s study of 1993, is rebutted. That estimate was associated with comorbid Oppositional Defiant Disorder (ODD) and/or Conduct Disorder (CD), not with ADHD, but the assertion has incorrectly been maintained for two decades. The present study provides some support for the hypothesis that the relative accident risk of ADHD-drivers with comorbid ODD, CD and/or other conduct problems, is higher than that of ADHD-drivers without these comorbidities. The estimated RRs were 1.86 (1.27; 2.75) in a sample of ADHD drivers in which a majority had comorbid ODD and/or CD compared to 1.31 (0.96; 1.81) in a sample of ADHD-drivers with no comorbidity. Given that ADHD-drivers most often seem to drive more than controls, and the fact that a majority of the present studies lack information about exposure, it seems more probable that the true RR is lower rather than higher than 1.23. Also the assertion that ADHD drivers violate traffic laws more often than other drivers should be modified: ADHD-drivers do have more speeding violations, but no more drunk or reckless driving citations than drivers without ADHD. All accident studies included in the meta-analysis fail to acknowledge the distinction between deliberate violations and driving errors. The former are known to be associated with accidents, the latter are not. A hypothesis that ADHD-drivers speed more frequently than controls because it stimulates attention and reaction time is suggested. PMID- 24238843 TI - Brain activation in teenagers with isolated spelling disorder during tasks involving spelling assessment and comparison of pseudowords. fMRI study. AB - METHODS: The present study aimed at defining the specific traits of brain activation in teenagers with isolated spelling disorder in comparison with good spellers. fMRI examination was performed where the subject's task involved taking a decision 1/whether the visually presented words were spelled correctly or not (the orthographic decision task), and 2/whether the two presented letters strings (pseudowords) were identical or not (the visual decision task). Half of the displays showing meaningful words with an orthographic difficulty contained pairs with both words spelled correctly, and half of them contained one misspelled word. Half of the pseudowords were identical, half of them were not. The participants of the study included 15 individuals with isolated spelling disorder and 14 good spellers, aged 13-15. RESULTS: The results demonstrated that the essential differences in brain activation between teenagers with isolated spelling disorder and good spellers were found in the left inferior frontal gyrus, left medial frontal gyrus and right cerebellum posterior lobe, i.e. structures important for language processes, working memory and automaticity of behaviour. CONCLUSION: Spelling disorder is not only an effect of language dysfunction, it could be a symptom of difficulties in learning and automaticity of motor and visual shapes of written words, rapid information processing as well as automating use of orthographic lexicon. PMID- 24238844 TI - Correction of distortion in distressed mothers' ratings of their preschool-aged children's Internalizing and Externalizing scale score. AB - Increased maternal psychopathology may bias mothers' ratings about child psychopathology. In this study we examined whether internalizing and externalizing behavior problems in young children were biased through maternal psychopathology. The clinical sample comprised 247 preschool-age patients who attended the Family Day Hospital in Munster, Germany. Internalizing and externalizing behavior problems were assessed by the CBCL/1.5-5, and maternal psychopathology was assessed by the SCL-90-R Global Severity Index (GSI). Three theoretical perspectives were tested by comparing the model fit of three structural equation models, namely the accuracy, distortion, and combinatory model. All of the models aimed to integrate multi-informant ratings from mother, therapists, and kindergarten teachers, but differed in the question which paths had to be significant. The distortion model fit the data best and supported the notion that there was a psychopathology-related bias in mothers' ratings. On the basis of this finding, we developed correction formulas comparable to Muller and Furniss (2013), in order to statistically control for this distortion. We discussed post-hoc explanations about why mothers with increased psychopathology gave higher ratings on the CBCL/1.5-5, including a better recall of internalizing symptoms, less flexible and effective parenting, and more perceived distress by child externalizing behavior. PMID- 24238846 TI - Is oxidative stress induced by iron status associated with gestational diabetes mellitus? AB - Gestational diabetes mellitus (GDM) is a common pregnancy complication in high risk populations, and is associated with increased perinatal and long term outcomes for both mothers and newborns. Both its prevention and early management can be reinforced by identifying risks factors, particularly those factors influencing glucose metabolism. On the other hand, several epidemiological studies have shown an increased oxidative stress (OS) in pregnant women with GDM. Elevated OS was also reported in pregnant women supplemented with iron, which can generate OS and may also influence insulin resistance. This review summarizes the current state of knowledge, highlighting the potential relationship between OS induced by iron status and the development of GDM. PMID- 24238845 TI - Expression and significance of notch signaling pathway in salivary adenoid cystic carcinoma. AB - Notch signaling plays a role in stem cell biology, tumor formation, angiogenesis, and cell death. Targeting Notch pathway could serve as a therapeutic strategy in cancer. Little is known about the differential role of various components of the Notch pathway in salivary adenoid cystic carcinoma (AdCC). To investigate the association of the Notch pathway in AdCC carcinogenesis, we analyzed the Notch receptor (Notch-1, Notch-2, Notch-4) and Notch ligand (Jagged-1, Delta) expressions. The results showed elevated expression levels of all 5 proteins in AdCC tissue relative to normal salivary gland tissues. Jagged-1/Notch-2 coexpression was significantly associated with increased patient survival rate. The elevated expression level of these Notch receptors and ligands in AdCC points to Notch signaling as a key player in AdCC pathogenesis. Our data provide evidence for a relationship between Jagged-1/Notch-2 coexpression and better overall patient survival with AdCC. Targeting Notch signaling pathway may provide therapeutic benefits for these patients. PMID- 24238847 TI - Carotid artery stenting: the dust has not yet settled. PMID- 24238848 TI - Accuracy of dedicated risk scores in patients undergoing primary percutaneous coronary intervention in daily clinical practice. AB - BACKGROUND: Comparisons between dedicated risk scores in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) in real-world clinical practice are scarce. The aim of this study was to assess the diagnostic performance of the Global Registry of Acute Coronary Events (GRACE), Primary Angioplasty in Myocardial Infarction (PAMI), Thrombolysis in Myocardial Infarction (TIMI), and Zwolle scores in STEMI patients undergoing pPCI in contemporary clinical practice. METHODS: This was a prospective cohort study of consecutive patients with STEMI undergoing pPCI between December 2009 and November 2010 in a high-volume tertiary referral centre. The outcomes assessed were major cardiovascular events (MACEs) and death within 30 days. The diagnostic accuracy of the scores was assessed using receiver operating characteristic curves, and scores were compared using the DeLong method. RESULTS: During the study period, 501 patients were included. Within 30 days, 62 patients (12.4%) presented a MACE and 39 individuals (7.8%) died. All scores were statistically associated with death and MACE within 30 days (P < 0.01). The c-statistic and 95% confidence intervals for 30-day mortality were: GRACE, 0.84 (0.78-0.90); TIMI, 0.81 (0.74-0.87); Zwolle, 0.80 (0.73-0.87); and PAMI, 0.75 (0.68-0.82) (P < 0.01). There was no statistically significant difference regarding the accuracy of the TIMI, GRACE, and Zwolle scores for 30 day mortality, but the GRACE score was superior to the PAMI score (P < 0.01). CONCLUSIONS: The TIMI, GRACE, and Zwolle scores performed equally well as predictors of mortality in patients who underwent pPCI in current practice. These results suggest that these scores are suitable options for risk assessment in a real-world setting. PMID- 24238849 TI - Evaluation of iron, zinc, copper, manganese and selenium in oral hospital diets. AB - BACKGROUND & AIMS: Many trace elements are nutrients essential to humans, acting in the metabolism as constituents or as enzymatic co-factors. The iron, zinc, copper, manganese and selenium contents of hospital diets (regular, blend and soft) and of oral food complement (OFC) were determined, evaluating the adequacy of each element in relation to the nutritional recommendations (DRIs) and the percent contribution alone and with OFC. METHODS: Duplicate samples were taken of six daily meals and of the OFC on two non-consecutive days from a hospital in Belo Horizonte (MG, Brazil) in May and September of 2010 and January of 2011. The elements were determined by ICP OES. RESULTS: Of the diets, the soft diet showed the highest elements content. Offering the OFC was insufficient to provide adequate levels of the trace elements. CONCLUSION: The oral hospital diets were inadequate in relation to the RDAs for the trace elements studied and the use of the OFCs was insufficient to compensate the values. PMID- 24238851 TI - Radiation dose to the floor of mouth muscles predicts swallowing complications following chemoradiation in oropharyngeal squamous cell carcinoma. AB - OBJECTIVES: While radiation dose to the larynx and pharyngeal constrictors has been the focus of swallowing complications, the suprahyoid muscles, or floor of mouth (FoM) muscles, are critical for hyoid and laryngeal elevation and effective bolus diversion, preventing penetration and aspiration. We hypothesize that radiation dose to these muscles may be important in the development of dysphagia. MATERIALS AND METHODS: We studied 46 patients with OPSCC treated with CRT and who underwent baseline swallowing evaluations and post-treatment videofluoroscopic swallowing studies (VFSS) from 2007 to 2010. Patients with abnormal penetration aspiration scores (PAS>2) served as the study population and patients with normal PAS scores (<= 2) served as the control cohort. Three suprahyoid muscles and two extrinsic tongue muscles were individually delineated and collectively referred to as the FoM muscles. Radiation dose-volume relationships for these muscles were calculated. Univariate logistic regression analysis was used to determine parameters of significance between patients with normal or abnormal PAS scores. A multivariate regression analysis was subsequently performed to isolate the most statistically critical structures associated with abnormal PAS. RESULTS: Univariate analysis resulted in significance/borderline significance of multiple structures associated with abnormal PAS following irradiation. However, when a multivariate model was applied, only the mean dose to the floor of mouth and minimum dose to the geniohyoid were associated with post-radiation abnormal PAS. CONCLUSIONS: The dose and volume delivered to the collective FoM muscles may be associated with an increased risk of laryngeal penetration/aspiration to a greater degree than previously recognized organs at risk. PMID- 24238850 TI - Hyper- and hypometabolism are not related to nutritional status of patients on the waiting list for liver transplantation. AB - BACKGROUND & AIMS: Metabolic disorders and malnutrition are well known conditions reported in patients with liver disease (LD), but the relationship between them are underexplored. So, the aim of this study was to assess the resting energy expenditure (REE) of these patients, identifying the prevalence of hyper- and hypometabolism. In addition, to evaluate whether malnutrition and clinical variables were associated with REE and metabolic disorders. METHODS: The REE was measured by indirect calorimetry and predicted by the Harris and Benedict formula (REEHB). Nutritional status was assessed by different methods. The etiology, severity and complications of LD were also evaluated. RESULTS: A total of 81 patients were assessed. The measured REE was 1587.5 +/- 426.6 kcal. The REE was overestimated by the REEHB (REE:REEHB <0.8) in 7.4% and underestimated (REE:REEHB >1.2) in 24.7% of the patients. The REE was lower in malnourished patients (p < 0.05). However, hyper- and hypometabolism were not associated with nutritional status (p > 0.05). The REE and hypermetabolism were not associated with LD, but hypometabolic patients had a higher prevalence of Child C, and had higher values for MELD, INR and total bilirubin (p < 0.05). After multiple regression analyses, the REE was significantly associated (p < 0.05) with intracellular body water, arm muscle area and serum glucose. Serum glucose was only significantly associated (p < 0.05) with hypermetabolism, and INR with hypometabolism. CONCLUSION: Changes in resting metabolism are present but not universal. The hypermetabolism was associated with extrahepatic factors, and hypometabolism with the severity of LD. Under these conditions in the clinical setting, calculated energy requirements using the HB formula should be adjusted. PMID- 24238852 TI - Work, work environments and other factors influencing nurse faculty intention to remain employed: a cross-sectional study. AB - BACKGROUND: Given the role nurse faculty have in educating nurses, little is known about what influences their intention to remain employed (ITR) in academic settings. OBJECTIVES: Findings from a nurse faculty survey administered to test a conceptual model of factors hypothesized as influencing nurse faculty ITR are reported. DESIGN: A cross-sectional survey design was employed. SETTING: We included colleges and universities in Ontario, Canada. PARTICIPANTS: The population of Ontario nurse faculty who reported being employed as nurse faculty with the College of Nurses of Ontario (Canada) was included. Of the 1328 nurse faculty who were surveyed, 650 participated. METHODS: Participants completed a questionnaire with measures of work, work environment, job satisfaction, burnout and ITR. Regression analyses were conducted to test the model. RESULTS: Ten of 26 independent variables explained 25.4% of variance in nurse faculty ITR for five years. These variables included: proximity to retirement, quality of relationships with colleagues, being employed full time, having dependents, satisfaction with work-life balance, quality of education, satisfaction with job status, access to financial support for education from organization, access to required human resources and being unionized. CONCLUSIONS: Although not all influencing factors are modifiable, academic leadership should develop strategies that encourage nurse faculty ITR. Strategies that support collegial relationships among faculty, increase the number of full time positions, promote work-life balance, engage faculty in assessing and strengthening education quality, support faculty choice between full-time and part-time work, and ensure adequate human resources required to teach effectively will lead to heightened nurse faculty ITR. PMID- 24238853 TI - ACL reconstruction in a teenage athlete with fibular hemimelia. AB - Fibular hemimelia exists as a rare cause of ACL insufficiency. This case report concerns the diagnosis and treatment of anterior cruciate ligament insufficiency in a teenage football player with fibular hemimelia. While ACL reconstruction has been described to allow activities of daily living in this patient population, this is the first report in the literature of anterior cruciate ligament reconstruction in an athlete with fibular hemimelia. We believe that ACL reconstruction is a viable and beneficial treatment option in the care of a symptomatic patient with congenital absence of the ACL and can allow athletes with this condition to return not only to their previous functional level, but also to their previous level of play. PMID- 24238854 TI - Timing of diaphyseal femur fracture nailing: is the difference night and day? AB - INTRODUCTION: Most hospitals are faced with reduced personnel, resources, and provider fatigue or shift changes when day turns to night. For these reasons, some have suggested that diaphyseal femur fractures should be fixed during the daytime. The purpose of this study is to determine whether the time of surgery affects the post-operative difference in femoral version (DFV) and femoral length (DFL) between the fixed and uninjured sides following intramedullary nailing (IMN). MATERIALS AND METHODS: Over a 10-year period, 340 patients underwent IMN of a diaphyseal femur fracture (AO types 32-A to C) with a post-operative computed tomography scanogram for version measurement. Demographic and surgical data, including time operated was collected. "Daytime" was defined as 7:00 AM to 6:59 PM, while the remainder of the clock was "nighttime". Additionally, the night hours were split into 3 consecutive 4-h categories for further analysis. Stepwise, multivariate regressions were used to evaluate any effect of time of surgery on post-operative DFV or DFL. Other variables included in these statistical models were age, sex, mechanism of injury, open vs. closed fracture, trauma vs. non-trauma surgeon, and AO and Winquist classifications. RESULTS: Overall, 22.4% (76/340) of all fractures were fixed at night. The mean post operative DFV and DFL from the uninjured side in these patients was 8.9 degrees and 4.1 mm, respectively, compared to 9.0 degrees and 4.8 mm in those treated during the daytime. This difference was not statistically significant when accounting for other factors (p>0.05). There was no statistically significant difference in patients with >10 mm limb length discrepancy or >15 degrees DFV (p=1.0 for both). CONCLUSION: The time of day at which diaphyseal femur fractures are treated does not have an impact on post-operative femoral version or length. While certain other injuries may be better handled during daytime hours, acceptable IMN of mid-shaft femur fractures may be achieved during all hours at a level 1 trauma centre. PMID- 24238855 TI - Investigation of switch from ATM to ATR signaling at the sites of DNA damage induced by low and high LET radiation. AB - Upon induction of DNA damage by ionizing radiation (IR), members of the phosphatidylinositol 3-kinase-like kinase family of proteins namely ataxia telangiectasia mutated (ATM), DNA-PKcs, and ATM- and Rad3-related (ATR) maintain genomic integrity by mounting DNA damage response (DDR). Recent reports suggest that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated during end processing by nucleases at the break sites. These stretches of single stranded overhangs hold the clue for the transition from ATM to ATR signaling at broken DNA ends. We investigated whether differential processing of breaks induced by low and high LET radiation augments the phenomenon of switching from ATM to ATR kinase and hence a concomitant NHEJ to HR transition at the sites of DNA damage. 82-6 human fibroblasts were irradiated with 1 or 2Gy of gamma-rays and particle radiation of increasing LET in order to increase the complexity and variability of DNA double strand breaks (DSB) structures. The activation kinetics of ATM and ATR kinases along with their downstream substrates were determined utilizing Western blotting and immunofluorescence techniques. Our data provide evidence of a potential switch from ATM to ATR kinase signaling in cells treated with gamma-rays at approximately 2h post irradiation, with induction and completion of resection denoted by Rad51 foci resolution kinetics and observed with a significant decline of phosphorylated ATR kinase 8h after IR. On the other hand, irradiation with high LET 600MeV/u (56)Fe (180keV/MUm) and 170MeV/u (28)Si (99keV/MUm) particles show a similar Rad51 foci decay kinetics, however, exhibiting prolonged resection, evident by the persistent phosphorylated ATM and ATR kinase until 24h post irradiation. This residual effect, however, was significantly reduced for 250MeV/u (16)O particles of moderate LET (25keV/MUm) and absent for gamma-rays. Hence, our results support the hypothesis that the transition from ATM to ATR signaling at DNA break sites is extended for longer periods of time, indicated by sustained resection due to the complex type of damage induced, a hallmark of high LET radiation, which may contribute to its increased biological effectiveness. PMID- 24238856 TI - Body mass index as a determinant of brown adipose tissue function in healthy children. AB - OBJECTIVE: To determine whether body mass index (BMI) percentile and ethnicity influence skin temperature overlying brown adipose tissue (BAT) depots in the supraclavicular region in healthy children. STUDY DESIGN: Infrared thermography measured supraclavicular region temperature (T(SCR)) at baseline and after exposure to a mild cool stimulus (single hand immersion in water at 20.1 degrees C) for 5 minutes in children aged 6-11 years (n = 55). The studies were undertaken in a normal school environment. RESULTS: BMI percentile and ethnicity were significant predictors of baseline T(SCR), with an inverse relationship between BMI percentile persisting after adjustment for ethnicity. Twenty-four children demonstrated a significant rise in T(SCR) after exposure to the cool stimulus. BMI percentile was a significant predictor of T(SCR) response, although there was no effect of ethnicity on T(SCR) change after exposure to the cool stimulus. CONCLUSION: We have demonstrated a negative relationship between BMI percentile and both baseline T(SCR), colocating with the primary region of BAT, and the change in T(SCR) in response to the cool stimulus. Future studies aimed at determining the primary factors regulating BAT function in healthy children should be targeted at the goal of maintaining a healthy BMI trajectory during childhood. PMID- 24238857 TI - Incidence and Epidemiology of Intussusception among Infants in Ho Chi Minh City, Vietnam. AB - OBJECTIVE: To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. STUDY DESIGN: Between 2009 and 2011, we identified intussusception hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. RESULTS: We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100,000 infants. The mean age of intussusception was ~ 37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. CONCLUSION: Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception. PMID- 24238858 TI - At-risk children of at-risk parents: assessing common injuries to the children of teenage parents. AB - OBJECTIVE: To examine the common injuries in the children of teenage parents seen in the emergency department (ED) of a large level I trauma center. STUDY DESIGN: We used admission records for guarantor age to assess common injuries. RESULTS: The majority of the patients were white, in the care of the mother, and suffered accidental injuries, with bruising and skin marks the most common. Although children born to teenage parents are at an increased risk for child abuse, the rate of abuse in this study sample remained low. Falls and ingested objects were the leading mechanisms of injury in these patients, who were generally evaluated and discharged from the ED. CONCLUSION: This study highlights the common injuries and mechanisms to better understand how injuries are sustained in this unique population. The results of this study can be used for educational purposes both in the ED and in classroom-based parenting classes. Prevention efforts for teenage parents should be geared toward teaching better supervision and improving home safety. PMID- 24238859 TI - Understanding the pediatric dermatology workforce shortage: mentoring matters. AB - OBJECTIVES: To target pediatric dermatologists directly in order to evaluate their current demographics and the most important motivating factors that influenced their career choice. Pediatric dermatology is one of the pediatric subspecialties with an inadequate supply to meet current patient needs. STUDY DESIGN: A survey was designed to evaluate the training pathway, employment status, participation in teaching, and clinical practice characteristics of pediatric dermatologists. The survey was administered to attendants of the 2010 Society for Pediatric Dermatology annual meeting. Any remaining board certified pediatric dermatologists who had not previously responded were queried via Survey Monkey. RESULTS: There was a 71% response rate. The majority chose a career in pediatric dermatology early, often prior to starting a dermatology residency. The vast majority of respondents noted mentorship as the most important influence on their decision to pursue a career in pediatric dermatology. The most common obstacles cited by respondents were financial hardship and resistance of some dermatology programs to accept applicants previously trained in pediatrics. CONCLUSIONS: Our survey provides evidence to support the importance of early exposure to the field and, most importantly, to committed pediatric dermatologists who can serve as mentors. This information may be helpful in approaching solutions to the workforce shortage in the field of pediatric dermatology. PMID- 24238860 TI - Early-life risk factors for childhood wheeze phenotypes in a high-risk birth cohort. AB - OBJECTIVE: To define longitudinal childhood wheeze phenotypes and identify their early-life risk factors. STUDY DESIGN: Current wheeze was recorded 23 times up to age 7 years in a birth cohort at high risk for allergy (n = 620). Latent class analysis of wheeze responses identified 5 classes. Multinomial logistic regression estimated associations of probability-weighted wheezing classes with early-life factors. All phenotypes were compared with never/infrequent wheezers. RESULTS: Lower respiratory tract infection (LRTI) by 1 year (relative risk [RR], 3.00; 95% CI, 1.58-5.70), childcare by 1 year (RR, 1.51; 95% CI, 1.02-2.22), and higher body mass index (RR, 2.51; 95% CI, 1.09-5.81) were associated with increased risk of early transient wheeze, whereas breastfeeding was protective (RR, 0.54; 95% CI, 0.32-0.90). LRTI (RR, 6.54; 95% CI, 2.55-16.76) and aeroallergen sensitization (RR, 4.95; 95% CI, 1.74-14.02) increased the risk of early persistent wheeze. LRTI (RR, 5.31; 95% CI, 2.71-10.41), eczema (RR, 2.77; 95% CI, 1.78-4.31), aeroallergen sensitization (RR, 5.60; 95% CI, 2.86-10.9), and food sensitization (RR, 2.77; 95% CI, 1.56-4.94) increased the risk of intermediate-onset wheeze, whereas dog exposure at baseline (RR, 0.52; 95% CI, 0.32-0.84) and first-born status (RR, 0.49; 95% CI, 0.32-0.76) were protective. Heavy parental smoking at birth (RR, 3.18; 95% CI, 1.02-9.88) increased the risk of late-onset wheeze, whereas breastfeeding reduced it (RR, 0.34; 95% CI, 0.12 0.96). All wheeze classes except early transient had greater risk of wheeze at age 12 years compared with never/infrequent wheezers. CONCLUSION: We found distinct early-life risk factor profiles for each wheeze phenotype. These findings provide insight into possible wheeze mechanisms and have implications for identifying preventive strategies and addressing clinical management of early life wheeze. PMID- 24238861 TI - Impaired cognitive functioning in patients with tyrosinemia type I receiving nitisinone. AB - OBJECTIVE: To examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet. STUDY DESIGN: We performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development. RESULTS: Average total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 +/- 13 vs 91 +/- 13; P = .008). Both verbal and performance IQ subscores differed (77 +/- 14 vs 95 +/- 11; P < .05 and 70 +/- 11 vs 87 +/- 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 +/- 15 to 69 +/- 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration. CONCLUSION: Patients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein restricted diet. PMID- 24238862 TI - A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. AB - OBJECTIVE: To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates >= 28 to <= 44 weeks gestational age. STUDY DESIGN: Forty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), >= 28 to <36 weeks, and group II (n = 24), >= 36 to <= 44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, MUg/kg) followed by a maintenance dose (MD, MUg . kg(-1) . h(-1)) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale. RESULTS: During dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L . h(-1) . kg(-1)) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation. CONCLUSION: Dexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half life. PMID- 24238863 TI - Rehospitalization for childhood asthma: timing, variation, and opportunities for intervention. AB - OBJECTIVE: To assess the timing of pediatric asthma rehospitalization, variation in rate of rehospitalization across hospitals, and factors associated with rehospitalization at different intervals. STUDY DESIGN: Retrospective cohort analysis of 44,204 hospitalizations for children with asthma within 42 children's hospitals between July 2008 and June 2011. The main outcome measures were rehospitalization for asthma within 7, 15, 30, 60, 180, and 365 days of an index asthma admission. RESULTS: The rate of asthma rehospitalization ranged from 0.5% (n = 208) at 7 days to 17.2% (n = 7603) at 365 days. Black patients and patients with public insurance had higher odds of rehospitalization at 60 days and beyond (P <= .01 for both). Adolescents (12- to 18-year-old), patients with a diagnosis of a complex chronic condition, and patients with a prior year asthma admission had higher odds of rehospitalization at every time interval (P <= .001 for all). Significant hospital variation in case-mix adjusted rates of rehospitalization existed at each time interval (P <= .01 for all). Rates at 365 days were <= 10.9% for the top 10% of hospitals; if all hospitals achieved this rate, 36.6% of rehospitalizations might have been avoided. CONCLUSIONS: Significant variation in asthma rehospitalization rates exists across children's hospitals from 7 to 365 days after an index admission. Racial/ethnic and economic disparities emerge at 60 days. By 1 year, rehospitalizations account for 1 in 6 hospitalizations. Assessing asthma rehospitalizations at longer intervals may augment our current understanding of and approach to post-hospitalization care improvement. PMID- 24238864 TI - Self-reported prevalence and severity of xerostomia and its related conditions in individuals attending hospital for general health examinations. AB - The aim of this study was to investigate the prevalence, severity, and relationships between xerostomia and its related symptoms in individuals who attended hospital for general health examinations. Participants included 883 men and 618 women aged between 30 and 60 years. History of symptoms during the previous 6 months, current symptoms, and severity of current symptoms were evaluated using a questionnaire that included questions about xerostomia, burning mouth, taste disturbance, and oral malodor. The prevalence of xerostomia and its related symptoms was 60.2%; the prevalence of oral malodor was 52.3%, xerostomia 33.0%, burning mouth 13.6%, and taste disturbance 12.5%. Men in their 30s and women in their 60s showed significantly higher prevalence and greater severity of xerostomia, burning mouth, and taste disturbance compared with their counterparts. The prevalence of xerostomia, burning mouth, and taste disturbance, and the severity of xerostomia increased significantly with age in women. The prevalence and severity of these four symptoms were significantly related and the association was the highest between burning mouth and taste disturbance. In conclusion, xerostomia and its related symptoms were highly prevalent at all ages. The prevalence and severity of these symptoms were closely related. PMID- 24238865 TI - Mandibular coronoid fractures: treatment options. PMID- 24238866 TI - En bloc prefabrication of vascularized bioartificial bone grafts in sheep and complete workflow for custom-made transplants. AB - The aim of this pilot study was to determine, in a new experimental model, whether complex bioartificial monoblocs of relevant size and stability can be prefabricated in a defined three-dimensional design, in which the latissimus dorsi muscle serves as a natural bioreactor and the thoracodorsal vessel tree is prepared for axial construct perfusion. Eighteen sheep were included in the study, with six animals in each of three experimental groups. Vitalization of the beta-tricalcium phosphate-based constructs was performed by direct application of unmodified osteogenic material from the iliac crest (group A), in vivo application of nucleated cell concentrate (NCC) from bone marrow aspirate (group B), and in vitro cultivation of bone marrow stromal cells (BMSC) in a perfusion bioreactor system (group C). The contours of the constructs were designed digitally and transferred onto the bioartificial bone grafts using a titanium cage, which was bent over a stereolithographic model of the defined subvolume intraoperatively. At the end of the prefabrication process, only the axial vascularized constructs of group A demonstrated vital bone formation with considerable stability. In groups B and C, the applied techniques were not able to induce ectopic bone formation. The presented computer-assisted workflow allows the prefabrication of custom-made bioartificial transplants. PMID- 24238867 TI - Association between affective temperaments and regional gray matter volume in healthy subjects. AB - BACKGROUND: Affective temperaments such as cyclothymic and hyperthymic temperaments have been regarded as potential antecedents of bipolar disorder but the neural substrates underlying these temperaments have not been identified. The aim of this study is to determine whether these temperaments are associated with specific neural substrates in regional brain morphology in healthy subjects. METHODS: We conducted a cross-sectional neuroimaging study of 60 healthy subjects (30 males and 30 females) with affective temperaments. All participants underwent the Mini-International Neuropsychiatric Interview (MINI) to screen for the past and present psychiatric disorder. The scores of cyclothymic and hyperthymic temperaments were measured by the Temperament Scale of Memphis, Pisa, Paris and San Diego-Autoquestionnaire. We analyzed the association between voxel-based morphometry of the brain and these affective temperaments. RESULTS: Subjects classified as having high cyclothymic scores had a significantly larger gray matter volume of the left medial frontal gyrus (MFG) than low cyclothymic subjects. High hyperthymic males also had significantly larger gray matter volume of the left MFG than low hyperthymic males, but there was no difference in females. Subjects with both high cyclothymic and high hyperthymic temperaments demonstrated significantly larger gray matter volume of the left MFG than their counterparts. Region of interest analysis revealed that peaks of these clusters showed a significant positive correlation of the regional volume with temperament scores. LIMITATIONS: The subjects were relatively young and the number was relatively small. Due to the nature of a cross-sectional research design, we could not determine the causal relationship between temperament and the volume changes. CONCLUSIONS: These findings suggest that cyclothymic and hyperthymic temperaments in healthy subjects may have their morphological basis in the left MFG. PMID- 24238868 TI - Sex differences in cognitive functioning in patients with bipolar disorder who recently recovered from a first episode of mania: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM). AB - BACKGROUND: Studies investigating bipolar disorder (BD) showed that healthy patterns of sex differences in cognitive functioning are altered within this population, but is it unknown whether these alterations are present in BD patients early in their course of illness. METHODS: Patients with bipolar I disorder (36 males, 38 female), who had recently experienced their first manic or mixed episode were tested along with healthy controls (39 males, 59 females) similar in age, sex and premorbid IQ. Cognitive function was assessed through a comprehensive neuropsychological test battery. RESULTS: Significant group effects were found in a majority of administered tests (p<0.05) with patients performing worse than healthy controls. Significant sex effects (p<0.05) were observed on tasks of spatial working memory and sustained attention, with males performing better than females. No significant group by sex interaction was found in any of the tasks administered. LIMITATIONS: The cognitive battery employed in this study may not have been optimally sensitive in detecting sex differences. CONCLUSIONS: The results suggest that unlike patients with long standing multi-episode BD or schizophrenia, healthy cognitive sex differences are maintained in patients with early BD, following recovery from a first-episode of mania. These findings highlight the progressive nature of the illness and provide justification for an early intervention. PMID- 24238870 TI - The role of adult attachment style, birth intervention and support in posttraumatic stress after childbirth: a prospective study. AB - BACKGROUND: There is converging evidence that between 1% and 3% of women develop posttraumatic stress disorder (PTSD) after childbirth. Various vulnerability and risk factors have been identified, including mode of birth and support during birth. However, little research has looked at the role of adult attachment style in how women respond to events during birth. This study prospectively examined the interaction between attachment style, mode of birth, and support in determining PTSD symptoms after birth. METHOD: A longitudinal study of women (n=57) from the last trimester of pregnancy to three months postpartum. Women completed questionnaire measures of attachment style in pregnancy and measures of PTSD, support during birth, and mode of birth at three months postpartum. RESULTS: Avoidant attachment style, operative birth (assisted vaginal or caesarean section) and poor support during birth were all significantly correlated with postnatal PTSD symptoms. Regression analyses showed that avoidant attachment style moderated the relationship between operative birth and PTSD symptoms, where women with avoidant attachment style who had operative deliveries were most at risk of PTSD symptoms. LIMITATIONS: The study was limited to white European, cohabiting, primiparous women. Future research is needed to see if these findings are replicated in larger samples and different sociodemographic groups. CONCLUSIONS: This study suggests avoidant attachment style may be a vulnerability factor for postpartum PTSD, particularly for women who have operative births. If replicated, clinical implications include the potential to screen for attachment style during pregnancy and tailor care during birth accordingly. PMID- 24238869 TI - Comparing factor structure of the Mood Disorder Questionnaire (MDQ): In Italy sexual behavior is euphoric but in Asia mysterious and forbidden. AB - BACKGROUND: The introduction of screening questionnaires, such as the Mood Disorder Questionnaire (MDQ), has stimulated clinical and epidemiological studies on bipolar disorders. In this work, we studied the item response pattern of the MDQ in the Italian population and compared the results with those of the validation of the MDQ in Asian studies (Chinese and Korean), analyzing similarities and differences among the populations studied. METHODS: The sample was made up of 2278 participants, distributed as follows: 56.6% females, 50.8% living in the north-central Italy, and 33.7% living in rural areas. The factor analysis was run on the matrix of tetrachoric correlations. The psychometric properties of the MDQ were also studied using the Rasch logistic model. RESULTS: The parallel analysis found two significant components. The first includes symptoms referring to acceleration, danger and irritability as risky behaviors, social interaction problems and mental flow. The second includes symptoms referring to self-confidence and energy. With respect to the Korean/Chinese results, the Italian sample, item 11 ("much more sex"), appears related to self confidence and energy, while in Asia it is connected with items expressing risky behaviors and irritability. LIMITATIONS: Differences in the frequency of comorbid disorders in Asian and Italian populations should be considered. The results should be confirmed and compared with those of other populations. CONCLUSIONS: Cultural differences appear to be associated with a different symptomatic expression of bipolar spectrum disorders. Future research will investigate the role of gene-environment interaction in the genesis of these differences. PMID- 24238871 TI - Adaptation and validation of the depression, anxiety and stress scale (DASS) to Brazilian Portuguese. AB - BACKGROUND: Depression and anxiety have been associated with a range of symptoms that often overlap. Depression, Anxiety and Stress Scale-21 (DASS-21) is a single instrument to assess symptoms of depression, anxiety and stress. This study aimed to adapt and validate the DASS-21 for use in the Brazilian Portuguese language. METHODS: The DASS-21 has been adapted following the translation-back translation methodology from English to Portuguese. 242 subjects completed the following assessments: the DASS-21, the Beck Depression Index (BDI), Beck Anxiety Index (BAI) and the Inventory of Stress Symptoms of Lipp (ISSL). RESULTS: The Kaiser Meyer-Olkin (KMO) result was .949, indicating that the adequacy of the model was high. Cronbach's alpha was .92 for the depression, .90 for the stress, and .86 for the anxiety, indicating a good internal consistency for each subscale. The correlations between DASS scale and BDI scale, BAI scale and ISSL inventory were strong. The factorial analysis and distribution of factors among the subscales indicated that the structure of three distinct factors is adequate. LIMITATIONS: Older subjects over 65 years of age were not largely represented in this sample. A study specific to this elderly population should be conducted. Another limitation of the study was education level. The impact of low education in its applicability should be considered. CONCLUSIONS: The findings support the validity of the Brazilian Portuguese version of the DASS-21 and add to the evidence of the DASS-21 quality and ability to assess emotional states separately, eliminating the use of different instruments to assess these states. PMID- 24238872 TI - Genetics of human gene expression. AB - A steadily growing number of studies have identified and characterized expression quantitative trait loci (eQTLs) in human cell-lines, primary cells, and tissues. This class of variation has been shown to play a role in complex traits, including disease. Here, we discuss how eQTLs have the potential to accelerate discovery of disease genes and functional mechanisms underlying complex traits. We discuss how context-specificity of eQTLs is being characterized at an unprecedented scale and breadth, and how this both informs on the intricacy of human genome function, and has important ramifications for elucidating function of genetic variants of interest, particularly for those contributing to disease. PMID- 24238874 TI - A simplified approach for the reduction of specific closed anterior table frontal sinus fractures. AB - We describe a simplified approach to the management of closed anterior table fractures of the frontal sinus. Forty-seven patients were diagnosed with this type of fracture during a 3-year period. Of these, 6 had minimally-invasive periosteal raising of the anterior table through a small perieyebrow skin incision, and access to the fracture was through a small trephine or the edge of the fracture itself. We compared this with the more traditional approach of a coronal flap, which was associated with an increased duration of stay in hospital and the potential for neurological complications. Surgical intervention with a minimally-invasive trephine approach provides good cosmesis, minimal blood loss, intact neurological function, and rapid recovery. This makes it an important technique to consider in carefully selected patients. PMID- 24238873 TI - Genotype to phenotype via network analysis. AB - A prime objective of genomic medicine is the identification of disease-causing mutations and the mechanisms by which such events result in disease. As most disease phenotypes arise not from single genes and proteins but from a complex network of molecular interactions, a priori knowledge about the molecular network serves as a framework for biological inference and data mining. Here we review recent developments at the interface of biological networks and mutation analysis. We examine how mutations may be treated as a perturbation of the molecular interaction network and what insights may be gained from taking this perspective. We review work that aims to transform static networks into rich context-dependent networks and recent attempts to integrate non-coding RNAs into such analysis. Finally, we conclude with an overview of the many challenges and opportunities that lie ahead. PMID- 24238875 TI - Role of medical thermography in treatment of Frey's syndrome with botulinum toxin A. AB - Frey syndrome classically causes gustatory sweating and facial flushing. We describe 2 cases in which medical thermography was used to investigate the symptoms. Images were taken after patients chewed a sialagogue and 2 weeks later they were given injections of botulinum toxin A. Images taken 4 weeks after treatment showed a considerable reduction in sweating and facial flushing, which was supported by the results of quality of life questionnaires completed before and after treatment. Medical thermography is much cleaner than the Minor's starch iodine test. It identifies areas of gustatory sweating, changes in temperature, and vascular changes, which potentially enable treatment to be targeted accurately. PMID- 24238876 TI - Percutaneous cryoablation of liver metastases from breast cancer: initial experience in 17 patients. AB - AIM: To assess the feasibility, safety, and effectiveness of percutaneous cryoablation for the treatment of liver metastases from breast cancer. MATERIALS AND METHODS: This study included 39 liver metastases in 17 female breast cancer patients who underwent computed tomography (CT)-guided percutaneous cryoablation. The mean age of the cohort was 55 years (range 30-66 years). The tumour response was evaluated by CT performed before treatment, 1 month after treatment, and every 3 months thereafter. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was used to assess the patients' quality of life before, 1 week, 1 month, and 3 months after cryoablation. The primary endpoints were technique effectiveness, quality of life, and complications. RESULTS: The technical success rate was 92% with no major complication reported. At the 1-month follow-up, the primary technique effectiveness was 87.1% (34 of 39 tumours). At the 3-months follow-up, local tumour progression was observed in six of 39 lesions (15.4%). The 1-year survival from the time of cryoablation was 70.6%. The quality of life symptoms and functioning scales were preserved in patients alive at 3 months after cryoablation. The global quality of life, mean value of "pain" and "fatigue" between 3 months after cryoablation and prior to treatment showed statistically significant differences, but no clinical significance. CONCLUSIONS: Cryoablation is a safe and effective ablative therapy, providing a high rate of local tumour control in breast cancer liver metastases. PMID- 24238877 TI - Cruciferous vegetables, glutathione S-transferase polymorphisms, and the risk of colorectal cancer among Chinese men. AB - PURPOSE: To assess the associations between cruciferous vegetable (CV) intake, GST gene polymorphisms, and colorectal cancer (CRC) in a population of Chinese men. METHODS: Using incidence density sampling, CRC cases (N = 340) diagnosed before December 31, 2010 within the Shanghai Men's Health Study were matched to noncases (N = 673). CV intake was assessed from a food frequency questionnaire and by isothiocyanate levels from spot urine samples. GSTM1 and GSTT1 were categorized as null (0 copies) versus non-null (1 or 2 copies). Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between CV intake and GST gene variants with CRC, and statistical interactions were evaluated. RESULTS: CRC risk was not associated with CV intake, whether measured by self-report or by urinary isothiocyanate nor with GST gene variants. No statistical interactions were detected between CV intake and GST gene variants on the odds of CRC. Stratifying by timing of urine sample collection and excluding CRC cases diagnosed in the first 2 years did not materially alter the results. CONCLUSIONS: This study provides no evidence supporting the involvement of CV intake in the development of CRC in Chinese men. PMID- 24238879 TI - Differential natural organic matter fouling of ceramic versus polymeric ultrafiltration membranes. AB - Ceramic ultrafiltration membranes has drawn increasing attention in drinking water treatment sectors as an alternative to traditional polymeric counterparts, yet only limited information has been made available about the characteristics of ceramic membrane fouling by natural organic matter. The effects of solution chemistry including ionic strength, divalent ion concentration and pH on the flux behavior were comparatively evaluated for ceramic and polymeric ultrafiltration of synthetic water containing model natural organic matter. Filtration characteristics were further probed via resistance-in-series model analysis, fouling visualization using quantum dots, batch adsorption test, contact angle measurement, solute-membrane surface adhesion force measurement, and quantitative comparison of fouling characteristics between ceramic and polymeric membranes. The results collectively suggested that the effects of solution chemistry on fouling behavior of ceramic membranes were generally similar to polymeric counterparts in terms of trends, while the extent varied significantly depending on water quality parameters. Lower fouling tendency and enhanced cleaning efficiency were observed with the ceramic membrane, further promoting the potential for ceramic membrane application to surface water treatment. PMID- 24238878 TI - Prediction of anaerobic biodegradability and bioaccessibility of municipal sludge by coupling sequential extractions with fluorescence spectroscopy: towards ADM1 variables characterization. AB - Advanced dynamic anaerobic digestion models, such as ADM1, require both detailed organic matter characterisation and intimate knowledge of the involved metabolic pathways. In the current study, a methodology for municipal sludge characterization is investigated to describe two key parameters: biodegradability and bioaccessibility of organic matter. The methodology is based on coupling sequential chemical extractions with 3D fluorescence spectroscopy. The use of increasingly strong solvents reveals different levels of organic matter accessibility and the spectroscopy measurement leads to a detailed characterisation of the organic matter. The results obtained from testing 52 municipal sludge samples (primary, secondary, digested and thermally treated) showed a successful correlation with sludge biodegradability and bioaccessibility. The two parameters, traditionally obtained through the biochemical methane potential (BMP) lab tests, are now obtain in only 5 days compared to the 30-60 days usually required. Experimental data, obtained from two different laboratory scale reactors, were used to validate the ADM1 model. The proposed approach showed a strong application potential for reactor design and advanced control of anaerobic digestion processes. PMID- 24238880 TI - Evaluating the potential of improving residential water balance at building scale. AB - Earlier results indicated that, for an average household, self-sufficiency in water supply can be achieved by following the Urban harvest Approach (UHA), in a combination of demand minimization, cascading and multi-sourcing. To achieve these results, it was assumed that all available local resources can be harvested. In reality, however, temporal, spatial and location-bound factors pose limitations to this harvest and, thus, to self-sufficiency. This article investigates potential spatial and temporal limitations to harvest local water resources at building level for the Netherlands, with a focus on indoor demand. Two building types were studied, a free standing house (one four-people household) and a mid-rise apartment flat (28 two-person households). To be able to model yearly water balances, daily patterns considering household occupancy and presence of water using appliances were defined per building type. Three strategies were defined. The strategies include demand minimization, light grey water (LGW) recycling, and rainwater harvesting (multi-sourcing). Recycling and multi-sourcing cater for toilet flushing and laundry machine. Results showed that water saving devices may reduce 30% of the conventional demand. Recycling of LGW can supply 100% of second quality water (DQ2) which represents 36% of the conventional demand or up to 20% of the minimized demand. Rainwater harvesting may supply approximately 80% of the minimized demand in case of the apartment flat and 60% in case of the free standing house. To harvest these potentials, different system specifications, related to the household type, are required. Two constraints to recycle and multi-source were identified, namely i) limitations in the grey water production and available rainfall; and ii) the potential to harvest water as determined by the temporal pattern in water availability, water use, and storage and treatment capacities. PMID- 24238881 TI - Urban water management to increase sustainability of cities. PMID- 24238882 TI - Macular morphology in patients with optic nerve head drusen and optic disc edema. AB - PURPOSE: In this study we investigated macular morphology, including individual retinal layers, in patients with optic nerve head drusen (ONHD) and optic disc edema (ODE) compared with healthy participants, using high-resolution spectral domain optical coherence tomography (OCT). DESIGN: Prospective, cross-sectional, observational study. PARTICIPANTS: A total of 67 patients with ONHD, 36 patients with ODE, and 57 healthy participants. METHODS: High-resolution spectral domain OCT (Copernicus [OPTOPOL Technology S.A., Zawiercie, Poland] 3-MUm resolution, 7 * 7 * 2-mm volumetric scans) was used to image macula morphology. Average retinal nerve fiber layer (RNFL) thickness was measured using a semiautomated method with manual correction of the internal limiting membrane, RNFL, and retinal pigment epithelium (RPE). Retinal and RNFL thicknesses were measured and analyzed in 3 circular zones (Early Treatment Diabetic Retinopathy Study protocol). Individual retinal layers at the macula were quantified by analyzing tomograms using ImageJ (http://rsbweb.nih.gov/ij/; Accessed June 1, 2013). MAIN OUTCOME MEASURES: Average retinal and individual retinal layer thickness in patients with ODE or ONHD, and healthy controls. RESULTS: Patients with ONHD had thicker retinae in the inner annulus compared with patients with ODE and controls (significant in the temporal segment compared with those with ODE [P = 0.013] and in the superior segment compared with controls [P = 0.05]). Patients with ONHD had a significantly thinner inner plexiform layer (IPL) (P = 0.02), nerve fiber layer (P = 0.05), and RPE (P = 0.0001), and thicker ganglion cell layer (P = 0.003) and outer plexiform layer (OPL) (P < 0.001) compared with controls. Patients with ODE demonstrated the thickest retina and RNFL in the outer annulus (significant in the inferior segment compared with controls, P = 0.02 for both) with significant thickening in the IPL (P = 0.004), OPL (P < 0.003), and outer segment layer (P <= 0.02), and severe ganglion cell loss (P = 0.004) and RPE (P = 0.0001) thinning compared with healthy volunteers. CONCLUSIONS: Our study shows that optic nerve diseases are associated with selective changes in different retinal layers in patients with ODE and ONHD. These findings may be of diagnostic value and could be taken into consideration in assessing patients and studying the pathogenesis of these conditions. PMID- 24238883 TI - Optical coherence tomography following percutaneous coronary intervention with Excimer laser coronary atherectomy. AB - The indications for Excimer laser coronary atherectomy (ELCA) have been refined in modern interventional practice. With the expanding role for optical coherence tomography (OCT) providing high-resolution intra-coronary imaging, this article examines the appearance of the coronary lumen after ELCA. Each indication for ELCA is discussed and illustrated with a clinical case, followed by detailed analysis of the OCT imaging pre and post ELCA. The aim of the article is to provide information to interventional cardiologists to facilitate decision making during PCI, when ELCA has been used as part of the interventional strategy. PMID- 24238884 TI - Tattoos - an historical essay. PMID- 24238885 TI - Subcortical vascular dementia (SVaD) without hypertension (HTN) may be a unique subtype of vascular dementia (VaD). AB - Although HTN is the most important factor in the pathogenesis of SVaD, about 20% of patients with SVaD do not have HTN. We hypothesize that SVaD without HTN may have strong risk factors other than HTN, and the study on this group can elucidate the risk factors for SVaD. We included 332 patients with SVaD from the database of the Clinical Research Center for Dementia of South Korea (CREDOS) study. Among them, 26.2% of patients (87 out of 332) had no history of HTN. We analyzed the differences in risk factors, clinical features, and survival time of SVaD according to HTN. Contrary to our expectations, SVaD without HTN had less known vascular risk factors such as diabetes mellitus (DM), dyslipidemia, and obesity. In addition, SVaD without HTN had different clinical features including less depression, focal neurological signs or symptoms and more features of disinhibition. However, although SVaD without HTN had less known vascular risk factors that can shorten survival times, the survival times did not differ according to the presence of HTN. SVaD without HTN may be a unique subtype of SVaD and can be a target group for studies of unknown risk factors for SVaD. PMID- 24238887 TI - Comparison of the bioavailability of docosapentaenoic acid (DPA, 22:5n-3) and eicosapentaenoic acid (EPA, 20:5n-3) in the rat. AB - Based on the results from a human study which showed significantly reduced incorporation of DPA compared with EPA into chylomicrons, this study was designed to test if dietary DPA was significantly less absorbed than EPA. Male Sprague Dawley rats were randomly assigned to three groups of six, and were fed a semi synthetic high fat diet (23.5% fat) for 9 days. The test omega 3 fatty acids (EPA and DPA, 250mg/animal/day, free fatty acid form) or olive oil (250mg/animal/day) were added to the high fat diet on days 5, 6 and 7. Dietary EPA and DPA appeared in the faeces on days 6, 7 and 8, with the total amount of DPA excreted being 4.6 fold greater than that of EPA. The total amount of faecal fat did not differ significantly between the groups. At the conclusion of the study (day 9), it was found that liver DPA, EPA and total n-3 LC-PUFA levels were significantly increased by both DPA and EPA feeding compared with the olive oil fed control group. In the heart, DPA feeding increased the DPA content and both DPA and EPA feeding increased the total n-3 LC-PUFA levels. This study showed that DPA and EPA, both provided in free form, are metabolised differently, despite being chemically similar. PMID- 24238886 TI - Mussel oligopeptides protect human fibroblasts from hydrogen peroxide (H2O2) induced premature senescence. AB - Mussel bioactive peptides have been viewed as mediators to maximize the high quality of life. In this study, the anti-aging activities of mussel oligopeptides were evaluated using H2O2-induced prematurely senescent MRC-5 fibroblasts. 3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry displayed that exposure to H2O2 led to the loss of cell viability and cell cycle arrest. In addition, H2O2 caused the elevation of senescence associated-beta-galactosidase (SA-beta-gal) activity and formation of senescence associated heterochromatin foci (SAHF). It was found that pretreatment with mussel oligopeptides could significantly attenuate these properties associated with cellular senescence. Mussel oligopeptides also led to the increase of glutathione (GSH) level and mitochondrial transmembrane potential (Deltapsim) recovery. In addition, mussel oligopeptides resulted in an improvement in transcriptional activity of peroxiredoxin 1 (Prx1), nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin 1 (SIRT1). This study revealed that mussel oligopeptides could protect against cellular senescence induced by H2O2, and the effects were closely associated with redox cycle modulating and potentiating the SIRT1 pathway. These findings provide new insights into the beneficial role of mussel bioactive peptides on retarding senescence process. PMID- 24238888 TI - Association of plasma viremia with HIV-1 RNA levels in cervicovaginal lavage secretions in HIV-1 seropositive ART naive women from Pune, India. AB - BACKGROUND: Coherent drug/microbicide/vaccine development research would benefit through a precise knowledge of HIV dissemination and its persistence in the female genital tract. Understanding relationship between plasma viremia and cervicovaginal HIV shedding may help to unveil mechanisms underlying transmission, compartmentalization and pathogenesis. OBJECTIVES: To study the association between HIV-1 RNA levels in the plasma and CVL specimens. STUDY DESIGN: Whole blood, plasma and CVL specimens were collected from 36 ART naive HIV-1 seropositive women qualifying the study inclusion criteria. Absolute CD4 counts, plasma and CVL HIV-1 RNA levels were estimated using commercially available kits (BD MultiSETTM Kit, Becton Dickinson, US and Abbott RT, Abbott Molecular, Germany). Correlation between plasma and CVL viral load was estimated by the Spearman's rank correlation coefficient. Additionally, the correlation between CVL viral load and absolute CD4 counts was studied. RESULTS: HIV-1 viral load in the CVL specimens was successfully quantified using the Abbott RT. Twenty seven of 36 women (75%) had detectable HIV-1 RNA levels in plasma and CVL specimens. The CVL viral load did not show any correlation with plasma viral load (rho=0.281, p=0.096) and showed a 'moderate correlation' (rho=-0.563, p=0.0004) with absolute CD4 counts. CONCLUSIONS: Albeit, the Abbott RT is designed for estimating plasma HIV-1 RNA levels, the study reports its use for estimating HIV 1 RNA levels in the CVL specimens as well. In accordance with the previous studies, our results suggest that plasma and CVL viral load are not correlated and plasma viremia might not solely predict cervico vaginal HIV shedding. PMID- 24238889 TI - Dengue-4 false negative results by Panbio(r) Dengue Early ELISA assay in Brazil. AB - BACKGROUND: Dengue is a serious public health problem in numerous countries. The ability to rapidly diagnosis dengue is important for patient triage and management. Detection of dengue viral protein, NS1, represents a new approach to dengue diagnosis. OBJECTIVE: The present study aims to evaluate if there are false negative results using the NS1 Ag rapid assay (Panbio((r)) Dengue Early ELISA) in two different epidemiological situations (epidemic and non-epidemic). STUDY DESIGN: 220 serum samples from patients with clinical symptoms of classical dengue fever were tested by NS1 antigen capture ELISA and Multiplex-Nested-PCR. RESULTS: In samples collected in a non-epidemic period we found a 100% agreement of ELISA and RT-PCR in dengue negative samples and 85% agreement of ELISA and RT PCR in dengue positive samples. But when we tested samples during an epidemic period (large DENV-4 outbreak) we found 15% false negative results (p<0.05) in dengue negative samples. CONCLUSIONS: Due to false negative results for DENV-4, the sole use of the Panbio((r)) Dengue Early ELISA assay as a screening method for monitoring circulating dengue serotypes must be reevaluated. PMID- 24238890 TI - Immediate stent recoil in an anastomotic vein graft lesion treated by cutting balloon angioplasty. AB - Saphenous vein graft (SVG) anastomotic lesions can have significant fibromuscular hyperplasia and may be resistant to balloon angioplasty alone. Stents have been used successfully to treat these lesions. There are no reports of immediate stent recoil following such treatment in the literature. We describe immediate and persistent stent recoil in an anastomotic SVG lesion even after initial and post deployment complete balloon dilatation of the stent and its successful treatment by cutting balloon angioplasty. PMID- 24238891 TI - Cardiac amyloidosis: diagnosis using delayed enhancement cardiac magnetic resonance imaging sequences. PMID- 24238892 TI - Increased incidence of neonatal respiratory distress in infants with mucopolysaccharidosis type II (MPS II, Hunter syndrome). AB - Records were reviewed on all patients with mucopolysaccharidosis type II (Hunter syndrome) seen at a single institution from 1999 to 2013 to identify those with a history of neonatal intensive care. Eleven of 34 patients were in a neonatal intensive care unit and all had respiratory distress with 8 diagnoses of respiratory distress syndrome and 3 of transient tachypnea of the newborn. None of the infants were premature; four were delivered by cesarean section. These findings suggest that respiratory distress is more commonly observed in neonates with MPS II than in the general population. This may reflect airway disease already present in this disorder at the time of birth. PMID- 24238893 TI - The occurrence of adverse events potentially attributable to nursing care in medical units: cross sectional record review. AB - BACKGROUND: Ensuring the safety of hospitalized patients remains a major challenge for healthcare systems, and nursing services are at the center of hospital care. Yet our knowledge about safety of nursing care is quite limited. In fact, most earlier studies examined one, or at most two, indicators, thus presenting an incomplete picture of safety at an institutional or broader level. Furthermore, methodologies have differed from one study to another, making benchmarking difficult. OBJECTIVES: The aim of this study was to describe the frequencies of six adverse events widely considered in the literature to be nursing-sensitive outcomes and to estimate the degree to which these events could be attributed to nursing care. METHOD: Cross-sectional review of charts of 2699 patients hospitalized on 22 medical units in 11 hospitals in Quebec, Canada. The events included: pressure sores, falls, medication administration errors, pneumonias, urinary infections, and inappropriate use of restraints. Experienced nurse reviewers abstracted patients' charts based on a grid developed for the study. RESULTS: Patient-level risk for at least one of these six adverse events was 15.3%, ranging from 9% to 28% across units. Of the 412 patients who experienced an event, 30% experienced two or more, for a total of 568 events. The risk of experiencing an adverse event with consequences was 6.2%, with a unit level range from 3.2% to 13.5%. Abstractors concluded that 76.8% of the events were attributable to nursing care. CONCLUSION: While the measurement approach adopted here has limitations stemming from reliance on review of documentation, it provided a practical means of assessing several nursing-sensitive adverse events simultaneously. Given that patient safety issues are so complex, tracking their prevalence and impact is important, as is finding means of evaluating progress in reducing them. PMID- 24238894 TI - Subjective dysphagia in older care home residents: a cross-sectional, multi centre point prevalence measurement. AB - BACKGROUND: Dysphagia has been found to be strongly associated with aspiration pneumonia in frail older people. Aspiration pneumonia is causing high hospitalization rates, morbidity, and often death. Better insight in the prevalence of (subjective) dysphagia in frail older people may improve its early recognition and treatment. OBJECTIVE: First, to assess the prevalence of subjective dysphagia in care home residents in the Netherlands. Second, to assess the associations of subjective dysphagia with potential risk factors of dysphagia. DESIGN: Retrospective data-analysis of a cross-sectional, multi-centre point prevalence measurement. SETTING: 119 care homes in the Netherlands. PARTICIPANTS: Data of 8119 care home residents aged 65 years or older were included and analyzed. METHODS: Subjective dysphagia was assessed by a resident's response to a dichotomous question with regard to experiencing swallowing problems. If a resident was not able to respond (e.g. residents with dementia or aphasia), the question was answered by the ward care provider, or the resident's file was consulted for registered swallowing complaints and/or dysphagia. Several residents' data were collected: gender, age, (number of) diseases, the presence of malnutrition, the Care Dependency Scale score, and the body mass index. RESULTS: Subjective dysphagia was found in 751 (9%) residents. A final model for subjective dysphagia after multivariate backward stepwise regression analysis revealed eight significant variables: age (B -0.022), Care Dependency Scale score (B -0.985), 'malnutrition' (OR 1.58; 95% CI 1.31-1.90), 'comorbidity' (OR 1.07; 95% CI 1.01-1.14), and the disease clusters 'dementia' (OR 0.55; 95% CI 0.45 0.66), 'nervous system disorder' (OR 1.55; 95% CI 1.20-1.99), 'cardiovascular disease' (OR 0.81; 95% CI 0.67-0.99) and 'cerebrovascular disease/hemiparesis' (OR 1.74; 95% CI 1.45-2.10). CONCLUSION: It seems justified to conclude that subjective dysphagia is a relevant care problem in older care home residents in the Netherlands. Care Dependency Scale score, 'malnutrition', and the disease clusters 'dementia', 'nervous system disorder', and 'cerebrovascular disease/hemiparesis' were associated with the presence of subjective dysphagia in this study. Age, 'comorbidity' and 'cardiovascular disease' showed very small influence. PMID- 24238895 TI - Long-term effects of electrodermal biofeedback training on seizure control in patients with drug-resistant epilepsy: two case reports. AB - We report data from two patients, followed over 3 years after electrodermal biofeedback treatment. Patients were trained three times each week for four weeks to increase their sympathetic arousal using electrodermal biofeedback. This treatment was directed at enabling the patients to change their psychophysiological state as a countermeasure to prevent seizures. Both patients voluntarily kept a record of seizure frequency over the year preceding the treatment and continued to record their seizures for up to 3 years after the termination of biofeedback treatment. Both patients showed a marked reduction in seizure frequency (54.9% and 59.8%) during the month of biofeedback treatment. This improvement was maintained over the subsequent years. We highlight the therapeutic potential of biofeedback interventions that enable patients to volitionally control their state of physiological arousal in the management of drug-resistant epilepsy. PMID- 24238896 TI - The ZEPHyR study: a randomized comparison of linezolid and vancomycin for MRSA pneumonia. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) accounts for 10 40% of hospital-acquired pneumonia, and even more in intensive care units. The current guidelines for the treatment of MRSA nosocomial pneumonia include vancomycin and linezolid. The authors of 2 prospective randomized trials comparing vancomycin and linezolid in nosocomial pneumonia had concluded to the non-inferiority of linezolid. A slight superiority of linezolid was observed in the MRSA pneumonia subgroup, in terms of clinical success and survival, but no definite conclusion could be drawn. METHODS: A prospective randomized study was made to compare a fixed linezolid dose to dose-optimized vancomycin for the treatment of bacteriologically proven MRSA nosocomial pneumonia (ZEPHyR Study). RESULTS: Among the 165 patients treated by linezolid (57.6%) in the PP population, 95 were clinically cured at the end of the study, compared to 81 of the 174 patients treated by vancomycin (46.6%) (IC 95% of the difference 0.5% 21.6%, P=0.042). Nephrotoxicity in the mITT population reached 8.4% in the linezolid group compared to 18.2% in the vancomycin group. CONCLUSION: LNZ was superior to vancomycin for the treatment of MRSA nosocomial pneumonia. PMID- 24238897 TI - Influence of respiratory substrate in carbon steel corrosion by a Sulphate Reducing Prokaryote model organism. AB - Sulphate Reducing Prokaryotes (SRP) are an important group of microorganisms involved in biocorrosion processes. Sulphide production is recognized as a fundamental cause of corrosion and nitrate is often used as treatment. The present work analyses the influence of respiratory substrates in the metal, from off-shore installations, SRP influenced corrosion, using Desulfovibrio desulfuricans ATTC 27774 as model organism, since this can switch from sulphate to nitrate. Open Circuit Potential over 6days in different conditions was measured, showing an increase around 200 and 90mV for the different media. Tafel plots were constructed allowing Ecorr and jcorr calculations. For SRP in sulphate and nitrate media Ecorr values of -824 and -728mV, and jcorr values of 2.5 and 3.7MUAcm(-2), respectively, were attained indicating that in nitrate, the resultant corrosion rate is larger than in sulphate. Also, it is shown that the equilibrium of sulphide in the solution/gas phases is a key factor to the evolution of corrosion Nitrate prevents pitting but promotes general corrosion and increases the corrosion potential and iron dissolution 40 times when compared to sulphate. Our results demonstrate that nitrate injection strategy in oil fields has to be considered carefully as option to reduce souring and localized corrosion. PMID- 24238898 TI - Impact of Desulfovibrio alaskensis biofilms on corrosion behaviour of carbon steel in marine environment. AB - Sulfate reducing prokaryotes are associated with the steel deterioration. They build heterogeneous biofilms, capable of accelerating corrosion processes. In this study metabolic activity and the biofilm development of Desulfovibrio alaskensis were correlated to electrochemical response of carbon steel surface. In the exponential growth phase sulfide concentration reached its maximum of about 10mM. This phenomenon was responsible for the parallel increase in the corrosion potential (Ecorr) up to -720mV (vs. SCE). Subsequently, during the intensive biofilm formation and development another Ecorr peak (-710mV vs. SCE) occurred. Decrease in Ecorr was registered during the biofilm maturation and kept stable, being 20mV lower than in the control. While carbon steel was protected from the microbial attachment and exposed to metabolic products, only one potential maximum (-730mV vs. SCE) was recorded. Here Ecorr variations coincided with sulfide concentration changes and kept at 120mV lower vs. the control. Weight loss examinations revealed corrosion rates, which did not exceed 0.05mm/y. Confocal microscopy suggested the importance of extracellular proteins in the biofilm formation. Above 150 proteins were detected in the EPS matrix. Surface effects of biofilm and metabolic products were visualised, revealing the role of attached microorganisms in the localised corrosion. PMID- 24238899 TI - A systematic review of midwife-led interventions to address post partum post traumatic stress. AB - OBJECTIVE: to systematically identify interventions that midwives could introduce to address post-traumatic stress in women following childbirth. METHODS: a search strategy was developed and relevant papers were identified from databases including Cinahl, Cochrane Library, EMBASE, Maternity and Infant Care, MEDLINE, PsycINFO, and Web of Science. Key search terms used were post-traumatic stress, post partum, intervention, controlled trial and review. Papers eligible for inclusion were primary studies and reviews of research published from 2002-2012, focusing on interventions which could be implemented by midwives for the prevention and/or management of PTSD. For primary studies, RCTs, controlled clinical trials, and cohort studies with a control group were eligible. Eligible reviews were those with a specified search strategy and inclusion/exclusion criteria. Methodological quality was assessed using recognised frameworks. FINDINGS: six primary studies and eight reviews were eligible for inclusion. The majority of included studies or reviews focused on debriefing and/or counselling interventions; however the results were not consistent due to significant variation in methodological quality and use of dissimilar interventions. Two of the reviews considered the general management of post partum PTSD and one broadly covered anxiety during pregnancy and the post partum, incorporating a section on PTSD. The majority of women reported that the opportunity to discuss their childbirth experience was subjectively beneficial. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: no evidence-based midwifery interventions were identified from this systematic review that can be recommended for introduction into practice to address PTSD. It is recommended that future research in this area should incorporate standardised interventions with similar outcome measures to facilitate synthesis of results. Further research on interventions used in non maternity populations is needed in order to confirm their usefulness in addressing post partum PTSD. PMID- 24238900 TI - Low birth weight and subsequent poor weight gain. PMID- 24238901 TI - The synthesis and biodistribution of [(11)C]metformin as a PET probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1) in vivo. AB - In order to develop a new positron emission tomography (PET) probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1), (11)C-labelled metformin was synthesized and then evaluated as a PET probe. [(11)C]Metformin ([(11)C]4) was synthesized in three steps, from [(11)C]methyl iodide. Evaluation by small animal PET of [(11)C]4 showed that there was increased concentrations of [(11)C]4 in the livers of mice pre-treated with pyrimethamine, a potential inhibitor of MATEs, inhibiting the hepatobiliary excretion of metformin. Radiometabolite analysis showed that [(11)C]4 was not degraded in vivo during the PET scan. Biodistribution studies were undertaken and the organ distributions were extrapolated into a standard human model. In conclusion, [(11)C]4 may be useful as a PET probe to non invasively study the in vivo function of hepatobiliary transport and drug-drug interactions, mediated by MATE1 in future clinical investigations. PMID- 24238902 TI - Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition. AB - A novel class of phosphodiesterase 10A (PDE10A) inhibitors with reduced CYP1A2 inhibition were designed and synthesized starting from 2-{[(1-phenyl-1H benzimidazol-6-yl)oxy]methyl}quinoline (1). Introduction of an isopropyl group at the 2-position and a methoxy group at the 5-position of the benzimidazole ring of lead compound 1 resulted in the identification of 2-{[(2-isopropyl-5-methoxy-1 phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (25b), which exhibited potent PDE10A inhibitory activity with reduced CYP1A2 inhibitory activity compared to compound 1. PMID- 24238903 TI - Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity. AB - Several antiepileptic drugs exert their activities by inhibiting Na(+) currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X Ar') modulate Na(+) currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH2Ar', OCH2=X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides ((+)H3NCH2C6H4OCH2Ar' Cl(-)) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2' trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na(+) channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts. PMID- 24238904 TI - Synthesis, cytotoxic evaluation and molecular docking study of 2-alkylthio-4 (2,3,4-trimethoxyphenyl)-5-aryl-thiazoles as tubulin polymerization inhibitors. AB - A series of cis-restricted 2-alkylthio-4-(2,3,4-trimethoxyphenyl)-5-aryl-thiazole analogues of combretastatin A-4 were synthesized and investigated for inhibition of cell proliferation against three cancer cell lines, HT-29, MCF-7, and AGS, and a normal mouse fibroblastic cell line, NIH-3T3, using an MTT assay. The biological study showed that 2-(methylthio) substituted compounds showed little cytotoxic activity against the four cell lines. In contrast, the presence of the 2-(benzylthio) group on the thiazole ring resulted in a significant improvement in cytotoxic activity relative to the 2-(methylthio) substituted derivatives. Furthermore, the inhibition of tubulin polymerization by some potent compounds was evaluated. All the compounds studied were moderate tubulin polymerization inhibitors. The flow cytometry analysis confirmed that the synthesized compounds led to cell cycle arrest at the G2/M phase. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. PMID- 24238905 TI - Percutaneous ilio-sacral screw insertion. fluoroscopic techniques. PMID- 24238906 TI - Gender, socioeconomic and ethnic/racial disparities in cardiovascular disease: a time for change. AB - Cardiovascular disease (CVD) mortality rates have declined steadily over the past few decades but gender, socioeconomic and ethnic/racial disparities have not. These disparities impede cardiovascular health care reaching all those in need. The origins of disparities in CVD are numerous and wide-ranging, having largely evolved from inequalities in society. Similarly, disparities in CVD, interventions and outcomes will also vary depending on the minority or disadvantaged group. For this reason, strategies aimed at reducing such disparities must be stratified according to the target group, while keeping in mind that these groups are not mutually exclusive. There is a pressing need to move beyond what can be inferred from traditional cardiovascular risk factor profiling toward implementation of interventions designed to address the needs of these populations that will eventuate in a reduction of disparities in morbidity and mortality from CVD. This will require targeted and sustainable actions. Only by ensuring timely and equitable access to care for all through increased awareness and active participation can we start to close the gap and deliver appropriate, acceptable and just care to all, regardless of gender, socioeconomic status or ethnicity/race. PMID- 24238907 TI - Initial stability of press-fit acetabular components under rotational forces. AB - The primary goal of this study was to determine the initial press-fit stability in acetabular components without screw fixation. Mechanical testing was performed with the implantation of press-fit acetabular components in cadaveric specimens. No significant difference was found in load to failure testing between 1 and 2 mm of under-reaming. However, there was significant variability in bending forces required to create 150 MUm of micromotion ranging from 49.3 N to 214.4 N. This study shows that cups implanted in a press-fit fashion, which are felt to be clinically stable, have high degrees of variability in resisting load and may be at risk for loosening. There is a need for more objective intra-operative techniques to test cup stability. PMID- 24238908 TI - Involvement in meal preparation at home is associated with better diet quality among Canadian children. AB - OBJECTIVE: To examine the associations between home meal preparation involvement with diet quality and food group intake among children. METHODS: Grade 5 children aged 10-11 years (n = 3,398) were surveyed. Food intake was measured using the Harvard Youth/Adolescent Food Frequency Questionnaire, and diet quality was measured using the Diet Quality Index-International. Random effects regression models with children nested within schools were used to test for associations. RESULTS: Higher frequency of involvement in home meal preparation was associated with higher Diet Quality Index-International scores. Children who were involved in meal preparation daily ate 1 more serving/d of vegetables and fruit compared with children who never helped (P < .001). Similar significant differences, although small, were observed for intake of the other food groups. CONCLUSIONS AND IMPLICATIONS: Children who were more involved in home meal preparation also consumed healthier diets. Encouraging parents to involve their children in meal preparation could be a viable health promotion strategy. PMID- 24238909 TI - Few changes in food security and dietary intake from short-term participation in the Supplemental Nutrition Assistance Program among low-income Massachusetts adults. AB - OBJECTIVE: To examine whether short-term participation in the Supplemental Nutrition Assistance Program (SNAP) affects food security and dietary quality among low-income adults recruited from a Massachusetts-wide emergency food hotline. METHODS: A 3-month, longitudinal study was conducted among 107 adults recruited at the time of SNAP application assistance. Outcomes included household food security (10-item US Department of Agriculture Food Security Survey Module), dietary intake (eg, grains, fruit) and diet quality (modified Alternate Healthy Eating Index). Data were analyzed using paired t tests and multivariable linear regression. RESULTS: Supplemental Nutrition Assistance Program participation was not associated with improved household food security over 3 months (P = .25). Compared with non-participants, SNAP participants increased refined grain intake by 1.1 serving/d (P = .02), from baseline to follow-up. No associations were observed with other foods, nutrients, or dietary quality. CONCLUSION AND IMPLICATIONS: Policies that simultaneously improve household food security and dietary quality should be implemented to support the health of low-income Americans participating in this crucial program. PMID- 24238910 TI - Impact of personal preference and motivation on fruit and vegetable consumption of WIC-participating mothers and children in Atlanta, GA. AB - OBJECTIVE: To determine the effect of psychosocial and sociodemographic factors on consumption of fruits and vegetables (F&V) for women and children participating in the Atlanta Special Supplemental Nutrition Program for Women, Infants, and Children. METHODS: Participants (n = 249) were selected from 2 Atlanta Special Supplemental Nutrition Program for Women, Infants, and Children agencies. Data from this analysis were collected from in-person interviews. The dichotomous dependent variable was whether participants met recommended intakes for F&V. Independent variables were personal preference and motivation factors of F&V consumption, and sociodemographic factors. Bivariate analysis determined significant factors to include in logistic models. RESULTS: Only 27.7% of mothers and 44.2% of their oldest child consumed > 5 servings of F&V daily. Not knowing how to prepare F&Vs and spoilage of F&V before eating them were significantly related to F&V consumption of mothers. CONCLUSIONS AND IMPLICATIONS: Food storage and preparation resulted in significant differences in meeting criteria for F&V consumption. Future initiatives should include cooking classes and emphasize food preparation techniques. PMID- 24238911 TI - Differences between juvenile offenders with and without substance use problems in the prevalence and impact of risk and protective factors for criminal recidivism. AB - BACKGROUND: Little is known about the needs of substance-using juveniles in treatment aimed at reducing criminal recidivism. Therefore, we aimed to examine treatment needs of substance-using juvenile offenders. METHODS: Differences were examined between juvenile offenders who abstain from substance use (ASU; n=1974) and substance-using juvenile offenders without (SU; n=7000) and with substance use problems (SUP; n=3317), in the prevalence of risk/protective factors for criminal recidivism and strength of associations between risk/protective factors and criminal recidivism. We conducted secondary data analysis on recidivism risk assessments, collected with the Washington State Juvenile Court Assessment, and re-offending data. Analyses of variance and Partial correlations, adjusted for age, gender and ethnicity were applied, as well as Fisher's z tests and logistic regression analyses. RESULTS: Results showed that substance-using offenders, especially those with substance use problems, had more risk factors and less protective factors than ASU youths in the domains of school, use of free time, relationships, family, attitude, aggression and skills. The associations between most of the risk/protective factors and recidivism were stronger in the ASU group than in the SUP group. Substance use uniquely predicted recidivism, net of risk factors. CONCLUSIONS: These results suggest that general interventions for juvenile offenders addressing risk and protective factors with the aim to reduce recidivism may be less effective for offenders with substance use problems, and that substance use (problems) should be addressed, too. PMID- 24238912 TI - PCB contamination in fish community from the Gironde Estuary (France): blast from the past. AB - The contamination of the Gironde Estuary, southwest of France, by polychlorinated biphenyls (PCBs) was assessed using six fish of high ecological and economic importance as bioindicator species. The concentrations of 21 PCB congeners and total fat contents were determined in the muscle and liver of eels (Anguilla anguilla), seabass (Dicentrarchus labrax), flounders (Platichthys flesus), meagres (Argyrosomus regius), mullets (Liza ramada), and soles (Solea vulgaris). In addition, information regarding the trophic ecology of the studied fish was obtained through the analysis of carbon and nitrogen stable isotopes (i.e., delta(13)C and delta(15)N) in muscle. Results revealed high PCB concentrations in fish compared to monitored European estuaries. The muscle of eels was by far the most contaminated fish flesh (Sigma7PCBs=1000+/-440 ng g(-1) on a dry weight basis), while the higher PCB concentrations in liver were measured in flounder (Sigma7PCBs=2040+/-1160 ng g(-1) d.w.). A quantile regression approach allowed to investigate the fate of PCBs in the Gironde estuarine fish assemblage, and revealed a general process of trophic magnification. Finally, most of the analysed fish presented PCB concentrations in muscle meat above the current European maximum limits for sea products, while the derived "Toxic Equivalent Quantity" (TEQ) revealed human health concerns only for high-fat fish consumption. PMID- 24238914 TI - Use of continuous and grab sample data for calculating total maximum daily load (TMDL) in agricultural watersheds. AB - Measuring the discharge of diffuse pollution from agricultural watersheds presents unique challenges. Flows in agricultural watersheds, particularly in Mediterranean climates, can be predominately irrigation runoff and exhibit large diurnal fluctuation in both volume and concentration. Flow and pollutant concentrations in these smaller watersheds dominated by human activity do not conform to a normal distribution and it is not clear if parametric methods are appropriate or accurate for load calculations. The objective of this study was to compare the accuracy of five load estimation methods to calculate pollutant loads from agricultural watersheds. Calculation of loads using results from discrete (grab) samples was compared with the true-load computed using in situ continuous monitoring measurements. A new method is introduced that uses a non-parametric measure of central tendency (the median) to calculate loads (median-load). The median-load method was compared to more commonly used parametric estimation methods which rely on using the mean as a measure of central tendency (mean-load and daily-load), a method that utilizes the total flow volume (volume-load), and a method that uses measure of flow at the time of sampling (instantaneous-load). Using measurements from ten watersheds in the San Joaquin Valley of California, the average percent error compared to the true-load for total dissolved solids (TDS) was 7.3% for the median-load, 6.9% for the mean-load, 6.9% for the volume load, 16.9% for the instantaneous-load, and 18.7% for the daily-load methods of calculation. The results of this study show that parametric methods are surprisingly accurate, even for data that have starkly non-normal distributions and are highly skewed. PMID- 24238913 TI - The Freundlich adsorption isotherm constants and prediction of phosphorus bioavailability as affected by different phosphorus sources in two Kansas soils. AB - Phosphorus (P) adsorption onto soil constituents influences P bioavailability from both agronomic and environmental perspectives. In this study, the P availability from different P sources along with utility of Freundlich adsorption coefficients on the predictability of various crop growth parameters were assessed. Two soils were amended with 150mgPkg(-1) each from six different P sources comprised of manures from two types of ruminants animals, three types of monogastric animals, and inorganic P fertilizer. Corn (Zea mays) was grown and harvested seven times under greenhouse conditions to remove P from the P amended treatments. The application of all P sources reduced the value of Freundlich K and increased the value of Freundlich 1/n and equilibrium P concentration (EPC0) in both soils compared to the un-amended control before cropping. The swine (Sus scrofa) manure (HM) resulted in significant smaller values of Freundlich K and larger values of 1/n in the P deficient Eram-Lebo soil compared to other P sources while, the opposite was true for the turkey (Meleagris gallopava) litter (TL) in the Ulysses soil. The corn biomass, tissue P concentration and P uptake were significantly influenced by all P sources during the first harvest and the total P uptake during seven harvests in both soils compared to the control treatment. Both Freundlich coefficients had strong relationships with the aforementioned corn parameters in the P deficient Eram-Lebo soil while, strength of the association was weak or missing in the Ulysses soil which had optimum levels of antecedent P. PMID- 24238915 TI - Evaluation of the efficiency of an experimental biocover to reduce BTEX emissions from landfill biogas. AB - Landfill emissions include volatile organic compounds (VOCs) and, particularly, benzene, toluene, ethyl-benzene and xylene isomers (collectively called BTEX). The latter are the most common VOCs found in landfill biogas. BTEX affect air quality and may be harmful to human health. In conjunction with a study aiming to evaluate the efficiency of passive methane oxidizing biocovers, a complementary project was developed with the specific goal of evaluating the reduction in VOC emissions due to the installation of a biocover. One of the biocovers constructed at the Saint-Nicephore (Quebec, Canada) landfill site was instrumented for this purpose. The total BTEX concentration in the raw biogas ranged from 28.7 to 65.4ppmv, and the measured concentration of BTEX in biogas emitted through the biocover ranged from below the limit of detection (BLD) to 2.1ppmv. The other volatile organic compounds (OVOCs) concentration varied from 18.8 to 40.4ppmv and from 0.8 to 1.2ppmv in the raw biogas and in the emitted biogas, respectively. The results obtained showed that the biocover effectiveness ranged from 67% to 100% and from 96% to 97% for BTEX and OVOC, respectively. PMID- 24238916 TI - Elucidation of the thermophilic phenol biodegradation pathway via benzoate during the anaerobic digestion of municipal solid waste. AB - Anaerobic digestion makes it possible to valorize municipal solid waste (MSW) into biogas and digestate which are, respectively, a renewable energy source and an organic amendment for soil. Phenols are persistent pollutants present in MSW that can inhibit the anaerobic digestion process and have a toxic effect on microbiota if they are applied to soil together with digestate. It is then important to define the operational conditions of anaerobic digestion which allow the complete degradation of phenol. In this context, the fate of phenol during the anaerobic digestion of MSW at 55 degrees C was followed using an isotopic tracing approach ((13)C6-phenol) in experimental microcosms with inoculum from an industrial thermophilic anaerobic digester. With this approach, it was possible to demonstrate the complete phenol biodegradation into methane and carbon dioxide via benzoate. Benzoate is known to be a phenol metabolite under mesophilic conditions, but in this study it was found for the first time to be a phenol degradation product at thermophilic temperature. PMID- 24238917 TI - Recent developments in assessment of long-term radionuclide behavior in the geosphere-biosphere subsystem. AB - Decisions on permitting, controlling and monitoring releases of radioactivity into the environment rely on a great variety of factors. Important among these is the prospective assessment of radionuclide behavior in the environment, including migration and accumulation among and within specific environmental media, and the resulting environmental and human health impacts. Models and techniques to undertake such assessments have been developed over several decades based on knowledge of the ecosystems involved, as well as monitoring of previous radionuclide releases to the environment, laboratory experiments and other related research. This paper presents developments in the assessment of radiation doses and related research for some of the key radionuclides identified as of potential significance in the context of releases to the biosphere from disposal facilities for solid radioactive waste. Since releases to the biosphere from disposal facilities involve transfers from the geosphere to the biosphere, an important aspect is the combined effects of surface hydrology, near-surface hydrogeology and chemical gradients on speciation and radionuclide mobility in the zone in which the geosphere and biosphere overlap (herein described as the geosphere-biosphere subsystem). In turn, these aspects of the environment can be modified as a result of environmental change over the thousands of years that have to be considered in radioactive waste disposal safety assessments. Building on the experience from improved understanding of the behavior of the key radionuclides, this paper proceeds to describe development of a generic methodology for representing the processes and environmental changes that are characteristic of the interface between the geosphere and the biosphere. The information that is provided and the methodology that is described are based on international collaborative work implemented through the BIOPROTA forum, www.bioprota.org. PMID- 24238918 TI - Retention and chemical speciation of uranium in an oxidized wetland sediment from the Savannah River Site. AB - Uranium speciation and retention mechanisms onto Savannah River Site (SRS) wetland sediments was studied using batch (ad)sorption experiments, sequential extraction, U L3-edge X-ray absorption near-edge structure (XANES) spectroscopy, fluorescence mapping and MU-XANES. Under oxidized conditions, U was highly retained by the SRS wetland sediments. In contrast to other similar but much lower natural organic matter (NOM) sediments, significant sorption of U onto the SRS sediments was observed at pH < 4 and pH > 8. Sequential extraction indicated that the U species were primarily associated with the acid soluble fraction (weak acetic acid extractable) and organic fraction (Na-pyrophosphate extractable). Uranium L3-edge XANES spectra of the U-bound sediments were nearly identical to that of uranyl acetate. Based on fluorescence mapping, U and Fe distributions in the sediment were poorly correlated, U was distributed throughout the sample and did not appear as isolated U mineral phases. The primary oxidation state of U in these oxidized sediments was U(VI), and there was little evidence that the high sorptive capacity of the sediments could be ascribed to abiotic or biotic reduction to the less soluble U(IV) species or to secondary mineral formation. Collectively, this study suggests that U may be strongly bound to wetland sediments, not only under reducing conditions by reductive precipitation, but also under oxidizing conditions through NOM-uranium bonding. PMID- 24238919 TI - Plutonium in wildlife and soils at the Maralinga legacy site: persistence over decadal time scales. AB - The mobility of plutonium (Pu) in soils, and its uptake into a range of wildlife, were examined using recent and ~25 year old data from the Taranaki area of the former Maralinga weapons test site, Australia. Since its initial deposition in the early 1960s, the dispersed Pu has been incorporated into the soil profile and food chain through natural processes, allowing for the study of Pu sequestration and dynamics in relatively undisturbed semi-arid conditions. The data indicate downward mobility of Pu in soil at rates of ~0.2-0.3 cm per year for the most mobile fraction. As a result, while all of the Pu was initially deposited on the ground surface, approximately 93% and 62% remained in the top 0-2 cm depth after 25- and 50-years respectively. No large-scale lateral spreading of the Taranaki plume was observed. Pu activity concentrations in 0-1 cm soils with biotic crusts were not elevated when compared with nearby bare soils, although a small number of individual data suggest retention of Pu-containing particles may be occurring in some biotic crusts. Soil-to-animal transfer, as measured by concentration ratios (CRwo-soil), was 4.1E-04 (Geometric Mean (GM)) in mammals, which aligns well with those from similar species and conditions (such as the Nevada Test Site, US), but are lower than the GM of the international mammal data reported in the Wildlife Transfer Database (WTD). These lower values are likely due to the presence of a low-soluble, particulate form of the Pu in Maralinga soils. Arthropod concentration ratios (3.1E-03 GM), were similar to those from Rocky Flats, US, while values for reptiles (2.0E-02 GM) were higher than the WTD GM value which was dominated by data from Chernobyl. Comparison of uptake data spanning approximately 30 years indicates no decrease over time for mammals, and a potential increase for reptiles. The results confirm the persistence of bioavailable Pu after more than 50 years since deposition, and also the presence of larger-sized particles which currently affect CRwo-soil calculations, and which may serve as an ongoing source of bioavailable Pu as they are subjected to weathering into the future. PMID- 24238920 TI - Increased intra-subject reaction time variability in the volitional control of movement in schizophrenia. AB - Increased Reaction Time (RT) studies intra-subject variability is an emerging and consistent finding in RT studies of schizophrenia. A group of 23 patients suffering from DSM-IV schizophrenia and a group of 23 age-matched control subjects performed two RT tasks requiring basic sensorimotor processing and engaging two different motor systems: the Finger Lift Reaction Time task and the Voluntary Saccade Reaction Time task. The Ex-Gaussian model was applied to the RT distributions measuring the mean (mu), and standard deviation (sigma) of a Gaussian component thought to reflect sensorimotor processing and an exponential component (tau), thought to reflect an intermediate decision process. In both tasks, a significantly larger RT intra-subject variability effectively dissociated patients from controls. RT intra-subject variability in the two tasks was highly correlated only for patients. Both sigma and tau were significantly higher in the patient group with tau being the best predictor of schizophrenia. Furthermore, only in the patient group were sigma and tau highly correlated between the two tasks. The results reflect a deficit in information processing that may not be confined to decision processes related to the frontal cortex; rather, they may indicate dysfunction in distributed neural networks modulating adaptive regulation of performance. PMID- 24238921 TI - Identification of methylguanine methyltransferase polymorphisms as genetic markers of individual susceptibility to therapy-related myeloid neoplasms. AB - PURPOSE: Myelodysplastic syndromes (MDS) are pre-leukaemic haematopoietic stem cell disorders. Among them, 10-20% occur after chemotherapy and/or radiotherapy, and are called 'therapy-related MDS' (t-MDS). The aim of this study was to identify genetic markers in t-MDS. METHODS: A prospective cohort of 59 MDS patients (39 de novo MDS, 20 t-MDS) was studied. A total of 384 single nucleotide polymorphisms (SNP) selected among genes involved in DNA repair, drug metabolism and transport, signal transduction and oncogenesis, were genotyped using a custom made SNP chip. RESULTS: Two non-synonymous SNPs present in the methylguanine methyltransferase (MGMT) gene, in complete linkage disequilibrium, were significantly associated with t-MDS: rs2308321 and rs2308327, with a raw p value of 7.4 * 10(-5) and a corrected p value after Benjamini-Hochberg correction of 0.014. Other associations tested between clinical and cytogenetic features and SNP chip gene variants gave corrected p values above 0.05. A validation cohort was separately constituted of 43 patients (24 de novo MDS, 19 t-MDS) and the two MGMT SNPs were genotyped; it confirmed a significant association between the variant allele of MGMT and t-MDS (p=0.038). CONCLUSION: We thus identified a putative marker of the risk to develop MDS after cancer treatment. PMID- 24238923 TI - Multimodal treatment strategies for elderly patients with head and neck cancer. AB - The population in developed countries is growing older and the number of elderly people annually diagnosed with head and neck cancers is expected to rapidly increase within the following decades, since these types of tumors are age dependent. The vast majority of older head and neck cancer patients present with locally advanced disease and multimodality treatment, including surgery, radiation and/or chemotherapy, is considered the best therapeutic option for these patients. However, several factors, including comorbidities, disabilities, frailty, and impaired functional status are considered to be more relevant criteria than chronological age per se for treatment planning. Therapeutic decisions are often complicated and demand the participation of many specialists. Advances in surgical and radiation techniques, along with the use of conventional chemotherapy and molecularly targeted agents, have improved treatment outcomes. The best-tailored individualized therapeutic option should be selected for these patients in order to avoid high toxicity and major functional deterioration. Still, more older-specific studies are needed in order to produce more definitive and applicable results. The aim of this review article is to investigate the multimodal treatment approaches for elderly patients with head and neck cancer. PMID- 24238922 TI - Innate immune mechanisms in vitiligo: danger from within. AB - Vitiligo is an autoimmune disease of the skin in which melanocytes are destroyed by antigen-specific T cells, resulting in patchy depigmentation. Although adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. Many studies report that cellular stress pathways are dysregulated in melanocytes from vitiligo patients, suggesting that melanocyte intrinsic defects participate in disease pathogenesis. Recent studies reveal that melanocyte stress generates damage-associated molecular patterns that activate innate immunity, thus connecting stress to organ-specific inflammation. Genetic studies in vitiligo support a role for stress, innate immunity, and adaptive mechanisms. Here, we discuss advances in the field that highlight how cellular stress, endogenous danger signals, and innate immune activation promote the onset of vitiligo. PMID- 24238924 TI - Fat crystallisation at oil-water interfaces. AB - This review focuses on recent advances in the understanding of lipid crystallisation at or in the vicinity of an interface in emulsified systems and the consequences regarding stability, structure and thermal behaviour. Amphiphilic molecules such as emulsifiers are preferably adsorbed at the interface. Such molecules are known for their ability to interact with triglycerides under certain conditions. In the same manner that inorganic crystals grown on an organic matrix see their nucleation, morphology and structure controlled by the underlying matrix, recent studies report a templating effect linked to the presence of emulsifiers at the oil/water interface. Emulsifiers affect fat crystallisation and fat crystal behaviour in numerous ways, acting as impurities seeding nucleation and, in some cases, retarding or enhancing polymorphic transitions towards more stable forms. This understanding is of crucial importance for the design of stable structures within emulsions, regardless of whether the system is oil or water continuous. In this paper, crystallisation mechanisms are briefly described, as well as recent technical advances that allow the study of crystallisation and crystal forms. Indeed, the study of the interface and of its effect on lipid crystallisation in emulsions has been limited for a long time by the lack of in-situ investigative techniques. This review also highlights reported interfacial effects in food and pharmaceutical emulsion systems. These effects are strongly linked to the presence of emulsifiers at the interface and their effects on crystallisation kinetics, and crystal morphology and stability. PMID- 24238926 TI - Ocular vestibular evoked myogenic potentials to head tap and cervical vestibular evoked myogenic potentials to air-conducted sounds in isolated internuclear ophthalmoplegia. AB - OBJECTIVE: The central pathways responsible for ocular vestibular evoked myogenic potentials (VEMPs) to forehead tapping remain to be determined. This study aimed to determine whether the medial longitudinal fasciculus (MLF) carries the signals for ocular VEMPs (oVEMPs) in response to this mode of stimulation. METHODS: Twelve patients with isolated unilateral internuclear ophthalmoplegia (INO) due to brainstem infarction underwent evaluation of the ocular tilt reaction (ocular torsion and skew deviation), tilt of the subjective visual vertical (SVV), cervical VEMPs (cVEMPs) in response to tone burst sound, and oVEMPs induced by tapping the forehead. RESULTS: Eight (67%) patients showed abnormal oVEMPs that included no wave formation (n=4) and decreased amplitude (n=3) in the lesion side, and bilaterally absent responses in the remaining patient. Furthermore, the patients showed diminished oVEMPs responses in the lesion side compared with normal side (6.0 +/- 5.6 vs. 11.7 +/- 5.5 MUV, paired t-test, p=0.001) and increased IADamp(%) of the oVEMPs compared with normal controls (43.6 +/- 41.2 vs. 9.1 +/- 6.2, t-test, p=0.018). In contrast, cVEMPs were abnormal in only three (25%) patients, decreased (n=2) or no response in the lesion side. Eleven (92%) patients showed contraversive ocular tilt reaction or SVV tilt. CONCLUSION: Patients with INO frequently show impaired formation of ipsilesional oVEMPs in response to forehead tapping. The occasional abnormality and decreased amplitude of ipsilesional cVEMPs also suggest a modulatory pathway for the inhibitory sacculocollic reflex descending in the MLF. SIGNIFICANCE: This study suggests that the MLF contains the fibers for the otolith-ocular reflex from the contralateral ear. PMID- 24238925 TI - Structural imaging in late-life depression: association with mood and cognitive responses to antidepressant treatment. AB - OBJECTIVES: Recent positron emission tomography studies of cerebral glucose metabolism have identified the functional neural circuitry associated with mood and cognitive responses to antidepressant treatment in late life depression (LLD). The structural alterations in these networks are not well understood. The present study used magnetic resonance (MR) imaging and voxel-based morphometry to evaluate the association between gray matter volumes and changes in mood symptoms and cognitive function with treatment with the antidepressant citalopram. DESIGN: Open-label trial with baseline brain MR scan. Mood and cognitive assessments performed at baseline and during citalopram treatment. SETTING: Outpatient clinics of an academic medical center. PARTICIPANTS: 17 previously unmedicated patients age 55 years or older with a major depressive episode and 17 non depressed comparison subjects. INTERVENTION: 12-week trial of flexibly dosed citalopram. MEASUREMENTS: Gray matter volumes, Hamilton Depression Rating Scale, California Verbal Learning Test, Delis-Kaplan Executive Function System. RESULTS: In LLD, higher gray matter volumes in the cingulate gyrus, superior and middle frontal gyri, middle temporal gyrus, and precuneus was associated with greater mood improvement. Higher gray matter volumes in primarily frontal areas were associated with greater improvement in verbal memory and verbal fluency performance. CONCLUSIONS: Associations with antidepressant induced improvements in mood and cognition were observed in several brain regions previously correlated with normalization of glucose metabolism after citalopram treatment in LLD. Future studies will investigate molecular mechanisms underlying these associations (e.g., beta-amyloid, inflammation, glutamate). PMID- 24238927 TI - A radiograph positioning technique to evaluate prosthetic misfit and bone loss around implants. AB - A radiograph positioning device was developed to fit with commercially available film holders and implant systems. The device is indexed to the dental implant body and the adjacent dentition by using an implant placement driver and polyvinyl siloxane occlusal registration material. By fitting the device to a conventional film holder, accurate orthogonal radiographs can monitor changes in bone architecture and prosthetic misfit. PMID- 24238928 TI - Radiation dosimetry of 18F-fluorocholine PET/CT studies in prostate cancer patients. AB - PURPOSE: We aimed to evaluate the Equivalent Doses (HTs) to highly exposed organs as well as the Effective Dose (ED) for (18)F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients. METHODS: Fifty patients were administered with (18)F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered (18)F-fluorocholine and CT scan, respectively, and the (18)F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure. RESULTS: The calculated (18)F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The (18)F-fluorocholine HTs to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the (18)F-fluorocholine did. CONCLUSIONS: For (18)F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered (18)F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures. PMID- 24238929 TI - The inclusion of activities of daily living in flexor tendon rehabilitation: a survey. AB - Studies have shown that patients restricted to one-handed use due to trauma or surgery often have difficulty with activities of daily living (ADLs). In order to assess hand therapists' perspectives and practices regarding ADL assessment and intervention, a 21-item survey was e-mailed to members of the American Society of Hand Therapists (ASHT). Results of the survey indicate that the majority of hand therapists surveyed (97.5%) feel that ADL performance is an important part of hand therapy practice and that teaching adaptive strategies is a high priority in the early weeks of flexor tendon rehabilitation, but less than half (45.5%) actually provide a formal assessment of ADL performance in order to discover patients' ADL needs. Reasons for this discrepancy between beliefs and practices are explored through participants' comments in the survey. LEVEL OF EVIDENCE: 3b. PMID- 24238930 TI - Current practice patterns in conservative thumb CMC joint care: survey results. AB - STUDY DESIGN: Cross-sectional descriptive survey INTRODUCTION: Best practice for conservative clinical care pathways is not well outlined in the literature for patients with thumb carpometacarpal joint (CMCJ) pain. This self-report survey investigated the current practice patterns of assessments and conservative interventions for the painful thumb CMCJ among hand therapists. METHODS: An online survey was distributed to members of the American Society of Hand Therapists (ASHT). Questions were included about evaluation measures and intervention techniques used for this population. A descriptive analysis was completed of the results. RESULTS: A total of 23.5% of the ASHT membership responded to the survey. Results were categorized using the International Classification of Functioning and Disability domains as a framework. The survey results report varying use of evaluation measures, therapeutic interventions, including orthotic fabrication, joint protection and patient education all therapeutic interventional techniques, and modalities. CONCLUSION: Therapists use a comprehensive array of evaluation measures and interventions for body functions and structures in the care of thumb CMC pain. In contrast, more consistent use is needed of psychometrically-sound functional outcome measures that show change in activities and participation. This survey highlights areas to employ current evidence, as well as, future research should address environmental factors and personal factors for this population LEVEL OF EVIDENCE: Not applicable. PMID- 24238931 TI - Biased processing of neutral facial expressions is associated with depressive symptoms and suicide ideation in individuals at risk for major depression due to affective temperaments. AB - BACKGROUND: To elucidate whether abnormal facial emotion processing represents a vulnerability factor for major depression, some studies have explored deficits in emotion processing in individuals at familial risk for depression. Nevertheless, these studies have provided mixed results. However, no studies on facial emotion processing have been conducted in at-risk samples with early or attenuated signs of depression, such as individuals with affective temperaments who are characterized by subclinical depressive moods, cognitions, and behaviors that resemble those that occur in patients with major depression. METHODS: Presence and severity of depressive symptoms, affective temperaments, death wishes, suicidal ideation, and suicide planning were explored in 231 participants with a mean age 39.9 years (SD=14.57). Participants also completed an emotion recognition task with 80 emotional face stimuli expressing fear, angry, sad, happy, and neutral facial expressions. RESULTS: Participants with higher scores on affective temperamental dimensions containing a depressive component, compared to those with lower scores, reported more depressive symptoms, death wishes, suicide ideation and planning, and an increased tendency to interpret neutral facial expressions as emotional facial expressions; in particular, neutral facial expressions were interpreted more negatively, mostly as sad facial expressions. However, there were no group differences in identification and discrimination of facial expressions of happiness, sadness, fear, and anger. CONCLUSIONS: A negative bias in interpretation of neutral facial expressions, but not accuracy deficits in recognizing emotional facial expressions, may represent a vulnerability factor for major depression. However, further research is needed. PMID- 24238932 TI - Demographics, clinical characteristics and quality of life of Brazilian women with driving phobia. AB - Driving phobia is associated with serious consequences such as restriction of freedom, career impairments and social embarrassment. The main objective of this paper is to compare clinical characteristics and quality of life between women with driving phobia and women without this phobia. These factors were assessed using structured interviews, semi-structured questionnaires, scales and inventories. We accessed diagnoses, depressive symptoms, anxiety symptoms, anxiety traits, driving cognitions and quality of life. There was no difference between groups with regard to demographic data and driving history. Both groups were also equivalent in the number of traumatic events and accidents experienced while driving or riding. The fear of driving group showed higher state and trait anxiety scores. A high frequency of cognitive distortions can explain why people with driving phobia often engage in maladaptive safety behaviors in an attempt to protect themselves from unpredicted dangers when driving. Regarding quality of life, the control group had slightly higher scores on all subscales, but significant differences were observed for only three scales: "functional capacity", "social aspects", and "mental health". More studies with larger samples more instruments and other contexts are needed to further investigate the clinical characteristics and personality traits of people who have a fear of driving. PMID- 24238933 TI - Phenomenology and correlates of insight in pediatric obsessive-compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is marked by the presence of obsessions and/or compulsions that cause significant interference in an individual's life. Insight regarding symptoms in youth with OCD may affect accurate assessment, acceptance and motivation for treatment, tolerance of negative valence states (i.e., fear) and treatment outcome, so assessment of this construct and associated clinical characteristics is important. Accordingly, the current study sought to expand the literature on symptom insight by examining multi-informant ratings of insight from children, parents, and clinicians simultaneously and its relationship to varied clinical characteristics. One-hundred and ten treatment seeking youth with a primary diagnosis of OCD, aged 6-17, participated in the study along with a parent/guardian. The nature of symptom conviction, fixity of ideas, and perceptions about the cause of the problems were important indicators in assessing child insight and resulted in a comprehensive, psychometrically sound measure of insight. Insight was generally not strongly associated with clinical characteristics. Poor insight was moderately associated with less resistance of obsessive-compulsive symptoms, increased externalizing symptoms, and ordering symptoms. Overall, this study contributes further information into the nature and correlates of insight in youth with OCD, and provides a psychometrically sound approach for its assessment. PMID- 24238934 TI - Stage migration in planning PET/CT scans in patients due to receive radiotherapy for non-small-cell lung cancer. AB - INTRODUCTION: This study examined rates of tumor progression in treatment-naive patients with non-small-cell lung cancer (NSCLC) as determined by repeat treatment-planning fluorine-18 ((18)F) fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). METHODS AND MATERIALS: This study assessed patients who underwent PET/CT simulation for NSCLC stage II/III, radiation-naive, nonmetastatic NSCLC. It compared planning PET/CT with previous PET/CT images. Patients were analyzed for change in stage, treatment intent, or both. Progression was defined as a change in TNM status leading to upstaging, and standardized uptake value (SUV) velocity was defined as [(SUVscan2 - SUVscan1)/interscan interval in days]. RESULTS: Of 149 consecutive patients examined between April 2009 and April 2011, 47 had prior PET/CT scans and were included. The median age was 68 years. New nodal disease or metastatic disease was identified in 24 (51%) of 47 patients. Fourteen (30%) had evidence of extrathoracic metastatic disease; the remaining 10 (21%) had new nodal disease that required substantial alteration of treatment fields. At a scan interval of 20 days, the rate of upstaging was 17%. SUV velocity was analyzed in the subset of patients who had their studies on the identical PET/CT scanner (n = 14). Nonupstaged patients had a mean SUV velocity of 0.074 units per day, compared with 0.11 units per day in patients that were upstaged by their second PET/CT scan (P = .020). CONCLUSION: Radiation treatment planning with hybrid PET/CT scans repeated within 120 days of an initial staging PET/CT scan identified significant upstaging in more than half of patients. For a subset of patients who underwent both scans on the same instrument, SUV velocity predicts upstaging, and the difference between those upstaged and those not was statistically significant. PMID- 24238935 TI - First-time fathers' experiences and needs during pregnancy and childbirth: a descriptive qualitative study. AB - OBJECTIVES: to explore first-time fathers' experiences and needs during their wives' pregnancy and childbirth in Singapore. DESIGN AND SETTING: a descriptive qualitative was conducted. Participants were recruited from two obstetric wards in a tertiary hospital in Singapore from November to December 2012. Semi structured, face-to-face interviews were used to collect data and themes from the interviews were generated using thematic analysis. PARTICIPANTS: a purposive sample of 16 first-time fathers aged above 21 years who accompanied their wives throughout pregnancy and childbirth were recruited from the postnatal wards between one to three days after the birth of their children. FINDINGS: four themes emerged from 16 subthemes: (1) Emotional changes experienced; (2) Adaptive and supportive behaviours adopted; (3) Social support received and (4) Suggestions for improvement to the current maternity care. First-time fathers experienced a range of emotions from being happy and excited to feeling shocked and worried and to feeling calm. Adaptive and supportive behaviours were adopted to deal with the pregnancy changes and better support their wives. In the course of their transition to fatherhood, they also received support from their family, friends, workplaces and the health care professionals. Fathers suggested more information, timely, empathetic and professional care be given and a review to the current administrative/logistical policies. CONCLUSIONS: all fathers modified their behaviours for the sake of protecting their wives and unborn children. Support from their family, friends, workplaces and the health care professionals was invaluable and greatly appreciated. IMPLICATIONS FOR PRACTICE: health care professionals can guide and support fathers by providing them with more information and preparing them for the unknown changes. Future studies are needed to develop intervention programme for fathers to improve their experiences and adaptive behaviours. PMID- 24238936 TI - Vibrational spectra, quantum chemical calculations and spectral assignments of 1,1-difluoro-1-silacyclohexane. AB - Raman spectra of 1,1-difluoro-1-silacyclohexane as a liquid, and as a solid at 78 K were recorded and depolarization data obtained. The infrared spectra of the vapour, liquid and amorphous and crystalline solids have been studied. In the low temperature IR and Raman spectra eight and three bands, respectively, were shifted a few cm(-1) when the sample crystallized. No bands vanished after crystallization in agreement with the assumption that only one conformer (chair) was present in all the states of aggregation. The compound exists in the stable chair conformation, whereas in the parent silacyclohexane a possible twist form should have more than 15 kJ mol(-1) higher energies than the chair, as derived from various calculations. The wavenumbers of the vibrational modes were calculated in the harmonic and anharmonic approximation employing B3LYP/cc-pVTZ calculations. The 27 A' and 21 A" fundamentals were assigned on the basis of the calculations, infrared vapour contours, Raman depolarization measurements and infrared and Raman band intensities. An average, relative deviation of 1.5% was found between the observed and the anharmonic wavenumbers for the 48 modes. PMID- 24238937 TI - Imaging of laryngeal trauma. AB - External laryngeal trauma is a rare but potentially life-threatening situation in the acutely injured patient. Trauma mechanism and magnitude, maximum focus of the applied force, and patient related factors, such as age and ossification of the laryngeal cartilages influence the spectrum of observed injuries. Their correct diagnosis and prompt management are paramount in order to avoid patient death or long-term impairment of breathing, swallowing and speaking. The current review provides a comprehensive approach to the radiologic interpretation of imaging studies performed in patients with suspected laryngeal injury. It describes the key anatomic structures that are relevant in laryngeal trauma and discusses the clinical role of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the acute emergency situation. The added value of two dimensional multiplanar reconstructions (2D MPR), three-dimensional volume rendering (3D VR) and virtual endoscopy (VE) for the non-invasive evaluation of laryngeal injuries and for treatment planning is discussed. The clinical presentation, biomechanics of injury, diagnostic pitfalls and pearls, common and uncommon findings are reviewed with emphasis of fracture patterns, involvement of laryngeal joints, intra- and extralaryngeal soft tissue injuries, and complications seen in the acute emergency situation. The radiologic appearance of common and less common long-term sequelae, as well as treatment options are equally addressed. PMID- 24238938 TI - Determination of the optimal energy level in spectral CT imaging for displaying abdominal vessels in pediatric patients. AB - PURPOSE: To determine the optimal energy level in contrast-enhanced spectral CT imaging for displaying abdominal vessels in pediatric patients. MATERIALS AND METHODS: This retrospective study was institutional review board approved. 15 children (8 males and 7 females, age range, 6-15 years, mean age 10.1+/-3.1 years) underwent contrast-enhanced spectral CT imaging for diagnosing solid tumors in abdomen and pelvic areas were included. A single contrast-enhanced scan was performed using a dual energy spectral CT mode with a new split contrast injection scheme (iodixanol at 1-1.5 ml/kg dose. 2/3 first, 1/3 at 7-15 s after the first injection). 101 sets of monochromatic images with photon energies of 40 140 keV with 1 keV interval were reconstructed. Contrast-noise-ratio (CNR) for hepatic portal or vein were generated and compared at every energy level to determine the optimal energy level to maximize CNR. 2 board-certified radiologists interpreted the selected image sets independently for image quality scores. RESULTS: CT values and CNR for the vessels increased as photon energy decreased from 140 to 40 keV: (CT value: 48.29-570.12 HU, CNR: 0.08-14.90) in the abdominal aorta, (58.48-369.73 HU, 0.64-5.87) in the inferior vena cava, and (58.48-369.73 HU, 0.06-6.96) in the portal vein. Monochromatic images at 40-50 keV (average 42.0+/-4.67 keV) could display vessels above three levels clearly, and with excellent image quality scores of 3.17+/-0.58 (of 4) (k=0.50). The CNR values at the optimal energy level were significantly higher than those at 70 keV, an average energy corresponding to the conventional 120 kVp for abdominal CT imaging. CONCLUSION: Spectral CT imaging provides a set of monochromatic images to optimize image quality and enhance vascular visibility, especially in the hepatic portal and vein systems. The best CNR for displaying abdominal vessels in children was obtained at 42 keV photon energy level. PMID- 24238939 TI - Dark blood versus bright blood T2 acquisition in cardiovascular magnetic resonance (CMR) for thalassaemia major (TM) patients: evaluation of feasibility, reproducibility and image quality. AB - OBJECTIVES: To compare the effectiveness of dark blood (DB) versus bright blood (BB) sequences. To assess the intra and inter-observer variability and inter study reproducibility between BB versus DB. To evaluate image quality level in the two sequences. METHODS: In a setting of 138 patients we performed CMR using cardiac gated Gradient-multiecho single breath-hold BB and DB sequences in the middle ventricular septum. Each acquisition was repeated during the same exam. Truncation method was used to account for background noise. Image quality (IQ) was assessed using a 5 point grading scale and image analysis was conducted by 2 experienced observers. RESULTS: Compared with the conventional BB acquisition, the coefficient of correlation and significance of the DB technique was superior for intra-observer reproducibility (p<0.001), inter-observer reproducibility (p<0.001) and inter-study reproducibility (p<0.001). The variability is also lower for DB sequences for T2* values <14 ms. Assessment of artifacts showed a superior score for DB versus BB scans (4 versus 3, p<0.001). CONCLUSIONS: Improvement in terms of inter observer and inter study variability using DB sequences was obtained. The greatest disparity between them was seen in inter study reproducibility and higher IQ in DB was seen. Study demonstrates better performance of DB imaging compared to BB in presence of comparable effectiveness. PMID- 24238940 TI - Characterization of LiBC by phase-contrast scanning transmission electron microscopy. AB - LiBC was used as a model compound for probing the applicability of phase-contrast (PC) imaging in an aberration-corrected scanning transmission electron microscope (STEM) to visualize lithium distributions. In the LiBC structure, boron and carbon are arranged to hetero graphite layers between which lithium is incorporated. The crystal structure is reflected in the PC-STEM images recorded perpendicular to the layers. The experimental images and their defocus dependence match with multi-slice simulations calculated utilizing the reciprocity principle. The observation that a part of the Li positions is not occupied is likely an effect of the intense electron beam triggering Li displacement. PMID- 24238941 TI - Development of hedge operator based fuzzy divergence measure and its application in segmentation of chronic myelogenous leukocytes from microscopic image of peripheral blood smear. AB - This paper introduces a hedge operator based fuzzy divergence measure and its application in segmentation of leukocytes in case of chronic myelogenous leukemia using light microscopic images of peripheral blood smears. The concept of modified discrimination measure is applied to develop the measure of divergence based on Shannon exponential entropy and Yager's measure of entropy. These two measures of divergence are compared with the existing literatures and validated by ground truth images. Finally, it is found that hedge operator based divergence measure using Yager's entropy achieves better segmentation accuracy i.e., 98.29% for normal and 98.15% for chronic myelogenous leukocytes. Furthermore, Jaccard index has been performed to compare the segmented image with ground truth ones where it is found that that the proposed scheme leads to higher Jaccard index (0.39 for normal, 0.24 for chronic myelogenous leukemia). PMID- 24238942 TI - Anterior chamber intraocular lens implantation in patients with a history of chronic uveitis: five-year follow-up. AB - PURPOSE: To compare the incidence of long-term complications after cataract surgery with primary anterior chamber intraocular lens (AC IOL) implantation in uveitic patients and patients without a history of intraocular inflammation (control group). SETTING: Single-center private practice. DESIGN: Retrospective clinical study. METHODS: The study comprised patients who between November 2005 and August 2010 had cataract extraction followed by AC IOL implantation because conventional placement was not possible. Outcome measures were the incidence of intraoperative and postoperative complications, preoperative corrected distance visual acuity (CDVA), and CDVA after 1 year. RESULTS: Of the 39 patients identified through electronic medical records, 17 (17 eyes) had a history of chronic uveitis and 22 (23 eyes) had no intraocular inflammatory disease. There were no significant differences in the incidence of intraoperative and postoperative complications between the 2 groups during follow-up (range 12 to 68 months) (P=.702). Although uveitic eyes had a greater risk for epiretinal membrane formation, the incidence of uveitis flareups attributed to the IOL and deposits on IOL surfaces was comparable to that in the control group (P<.001). The CDVA improved significantly in both groups 1 year after surgery (P<.01 and P<.001, respectively). CONCLUSION: In uveitic eyes with inadequate capsule support, AC IOL implantation restored visual function without a significant increase in long-term postoperative complications compared with eyes that had no history of uveitis. PMID- 24238943 TI - Posterior capsule opacification with 3 intraocular lenses: 12-year prospective study. AB - PURPOSE: To compare posterior capsule opacification (PCO) with 3 intraocular lenses (IOLs) 12 years postoperatively. SETTING: St. Erik Eye Hospital, Stockholm, Sweden. DESIGN: Randomized clinical trial. METHODS: Patients having unilateral standard phacoemulsification were randomized to implantation of a round-edged heparin-surface-modified (HSM) poly(methyl methacrylate) (PMMA) IOL, a round-edged silicone IOL, or a sharp-edged hydrophobic acrylic IOL. The neodymium:YAG (Nd:YAG) capsulotomy rates and timing from surgery were recorded. Survival analysis was used to compare Nd:YAG rates. Retroillumination images were taken to evaluate PCO. RESULTS: After 12 years, there was no significant difference in the fraction or severity of PCO between the silicone IOL and acrylic IOL. The HSM PMMA IOL had a significantly higher PCO fraction than the silicone IOL (P<.05), but not more than the acrylic IOL. There was no difference in PCO severity between the HSM PMMA IOL and the other 2 IOLs. The silicone IOL had higher median capsulotomy-free survival (>150 months) than the acrylic IOL (108 months) and the HSM PMMA IOL (53 months). Overall survival without Nd:YAG capsulotomy did not differ between the acrylic and silicone IOLs or between the silicone and HSM PMMA IOLs; however, overall survival was significantly better with the acrylic IOL than with the HSM PMMA IOL (P<.001). CONCLUSIONS: After 12 years, there was no difference in PCO or overall survival without capsulotomy between the acrylic IOL and the silicone IOL. The HSM PMMA IOL had a significantly higher PCO fraction than the silicone IOL and lower overall survival than the acrylic IOL. PMID- 24238944 TI - Clinical characteristics and surgical outcomes of phacoemulsification in true exfoliation syndrome. AB - PURPOSE: To review the clinical characteristics and surgical outcomes of patients with true exfoliation syndrome of the lens capsule having phacoemulsification cataract surgery. SETTING: Hong Kong Eye Hospital, Kowloon, Hong Kong. DESIGN: Case series. METHODS: Eyes of patients with true exfoliation syndrome diagnosed clinically or intraoperatively had standard phacoemulsification and intraocular lens (IOL) implantation. The anterior capsules removed during capsulorhexis were sent for histological confirmation. RESULTS: Twenty-four eyes of 18 patients were included. All eyes were confirmed to have true exfoliation syndrome by histological examination of the anterior lens capsule. Seven eyes (29.2%) had preexisting chronic glaucoma; 5 (20.8%) had laser iridotomy before the diagnosis. During phacoemulsification, all eyes had a continuous curvilinear capsulorhexis without complications. Trypan blue staining was used during capsulorhexis in 11 eyes (45.8%). Posterior capsule rupture occurred during lens chopping in 1 eye (4.2%). No loose zonular fibers or radial extension of capsulorhexis occurred. Capsular bag IOL implantation was successfully performed in all cases except the 1 with a posterior capsule rupture, in which an anterior chamber IOL was implanted. CONCLUSIONS: Phacoemulsification was safely performed in eyes with true exfoliation syndrome. Trypan blue staining can be used to facilitate capsulorhexis creation. Ultrasound biomicroscopy or anterior segment optical coherence tomography may be useful in preoperative assessment of such cases. The disease may be associated with glaucoma and laser iridotomy. PMID- 24238945 TI - A study of the association between chronic superficial keratitis and polymorphisms in the upstream regulatory regions of DLA-DRB1, DLA-DQB1 and DLA DQA1. AB - Canine chronic superficial keratitis (CSK) is an inflammatory corneal disease that primarily occurs in German shepherd dogs (GSDs). Several studies support the hypothesis that CSK is an immune-mediated disease. To investigate the genetic factors associated with CSK development, the upstream regulatory regions (URRs) of the DLA-DRB, -DQA and -DQB genes were genotyped in 60 dogs, including 32 CSK animals. LD analysis identified two blocks (r(2)<=45), with two DLA-DRB1 and five DLA-DQB1 haplotypes. Analysis of DLA-URR alleles/haplotypes showed a significant association between DQB1*-154 [C/T] (p=0.016) and CSK, suggesting that the T variant may increase the risk for developing CSK disease (OR=3, 95% CI=1.25 7.68). When haplotype associations were performed, the URR-DQB*CATT haplotype was significantly associated with CSK (p=0.016), increasing the risk of develop this disease over two-fold (OR=3, 95%, CI=1.25-7.68). These results showed that dogs homozygous at DRB1*69 [C/T] had a risk for developing CSK disease that was over four times the risk for heterozygotes. This genetic association supports the previous clinical, histological and pharmacological studies that suggest that CSK is an immune-mediated disease, and this association could potentially be used to identify susceptible animals. PMID- 24238946 TI - Immunochemical faecal occult blood tests for colorectal cancer screening: no time to lose. PMID- 24238947 TI - Cost effectiveness of newborn screening for cystic fibrosis: a simulation study. AB - BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1 IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec. PMID- 24238948 TI - CAQI Common Air Quality Index--update with PM(2.5) and sensitivity analysis. AB - The CAQI or Common Air Quality Index was proposed to facilitate the comparison of air quality in European cities in real-time. There are many air quality indices in use in the world. All are somewhat different in concept and presentation and comparing air quality presentations of cities on the internet was virtually impossible. The CAQI and the accompanying website www.airqualitynow.eu and app were proposed to overcome this problem in Europe. This paper describes the logic of making an index, in particular the CAQI and its update with a grid for PM2.5. To assure a smooth transition to the new calculation scheme we studied the behaviour of the index before and after the changes. We used 2006 Airbase data from 31 urban background and 27 street stations all across Europe (that were monitoring PM2.5 in 2006). The CAQI characterises a city by a roadside and urban background situation. It also insists on a minimum number of pollutants to be included in the calculation. Both were deemed necessary to improve the basis for comparing one city to another. A sensitivity analysis demonstrates the comparative behaviour of the street and urban background stations and presents the sensitivity of the CAQI outcome to the pollutants included in its calculation. PMID- 24238949 TI - Comparability of river quality assessment using macrophytes: a multi-step procedure to overcome biogeographical differences. AB - This paper exposes a new methodological approach to solve the problem of intercalibrating river quality national methods when a common metric is lacking and most of the countries share the same Water Framework Directive (WFD) assessment method. We provide recommendations for similar works in future concerning the assessment of ecological accuracy and highlight the importance of a good common ground to make feasible the scientific work beyond the intercalibration. The approach herein presented was applied to highly seasonal rivers of the Mediterranean Geographical Intercalibration Group for the Biological Quality Element Macrophytes. The Mediterranean Group of river macrophytes involved seven countries and two assessment methods with similar acquisition data and assessment concept: the Macrophyte Biological Index for Rivers (IBMR) for Cyprus, France, Greece, Italy, Portugal and Spain, and the River Macrophyte Index (RMI) for Slovenia. Database included 318 sites of which 78 were considered as benchmarks. The boundary harmonization was performed for common WFD-assessment methods (all countries except Slovenia) using the median of the Good/Moderate and High/Good boundaries of all countries. Then, whenever possible, the Slovenian method, RMI was computed for the entire database. The IBMR was also computed for the Slovenian sites and was regressed against RMI in order to check the relatedness of methods (R(2)=0.45; p<0.00001) and to convert RMI boundaries into the IBMR scale. The boundary bias of RMI was computed using direct comparison of classification and the median boundary values following boundary harmonization. The average absolute class differences after harmonization is 26% and the percentage of classifications differing by half of a quality class is also small (16.4%). This multi-step approach to the intercalibration was endorsed by the WFD Regulatory Committee. PMID- 24238950 TI - Environmental gradients and macroalgae in Mediterranean marshes: the case of Pego Oliva marsh (East Iberian Peninsula). AB - Although Mediterranean marshes have historically suffered high anthropogenic pressure, they have maintained their remarkable biodiversity. They are severely threatened but remain comparatively unexplored systems from the algological point of view. For example, most of the indexes proposed for monitoring ecological quality are based on diatoms and very few have explored the use of macroalgae. The Pego-Oliva marsh is located in the east of the Iberian Peninsula close to the Mediterranean coast with warm annual temperature and fairly high precipitation. The aims of this study were to ascertain the ecological variables that explained macroalgal distribution in the Pego-Oliva marsh and to assess their indicator value. Macroalgal biodiversity was seen to be high (50 taxa) despite the high nitrogen concentration of the marsh. All the environmental variables studied had a broad range of variation throughout the marsh, especially conductivity (500 12290 MUS/cm), temperature (14.3-31.7 degrees C), nitrate (9.493-64.113 mg/L) and ammonium (0.004-0.814 mg/L). A clear gradient of conductivity and dissolved oxygen was observed from fresh to saltwater. Batrachospermum arcuatum, Calothrix parietina, Chaetophora tuberculosa, Draparnaldia mutabilis, Hildenbrandia angolensis and Leptolyngbya angustissima were seen to act as indicators of low conductivity and dissolved inorganic nitrogen, and high dissolved oxygen, while Calothrix pulvinata, Ulva intestinalis, Homoeothrix violacea, Phormidium tergestinum and Thorea violacea were indicators of high conductivity and low dissolved nitrogen habitats. Cladophora glomerata, Compsopogon coeruleus, Polysiphonia subtilissima and Ulva flexuosa are the most widespread species and have a broad ecological range. Irrigation ditches have high ammonium and low dissolved oxygen concentrations and host infrequently reported species like Kumanoa mahlacensis. The data presented confirm the usefulness of macroalgae for the ecological monitoring of marshes, while increasing our knowledge of the distribution and ecological range of some species. However, more experimental work is needed to know the tolerance range of species living in dynamic systems like Mediterranean marshes. PMID- 24238951 TI - Effectiveness of Internet-based cognitive behaviour therapy for depression in routine psychiatric care. AB - BACKGROUND: Efficacy of guided Internet-based cognitive behaviour therapy (ICBT) for depression has been demonstrated in several randomised controlled trials. Knowledge on the effectiveness of the treatment, i.e. how it works when delivered within routine care, is however scarce. The aim of this study was to investigate the effectiveness of ICBT for depression. METHODS: We conducted a cohort study investigating all patients (N=1203) who had received guided ICBT for depression between 2007 and 2013 in a routine care setting at an outpatient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Montgomery Asberg Depression Rating Scale-Self rated (MADRS-S). RESULTS: Patients made large improvements from pre-treatment assessments to post-treatment on the primary outcome (effect size d on the MADRS-S=1.27, 99% CI, 1.14-1.39). Participants were significantly improved in terms of suicidal ideation and sleep difficulties. Improvements were sustained at 6-month follow-up. LIMITATIONS: Attrition was rather large at 6-month follow-up. However, additional data was collected through telephone interviews with dropouts and advanced statistical models indicated that missing data did not bias the findings. CONCLUSIONS: ICBT for depression can be highly effective when delivered within the context of routine psychiatric care. This study suggests that the effect sizes are at least as high when the treatment is delivered in routine psychiatric care by qualified staff as when delivered in a controlled trial setting. PMID- 24238952 TI - General distress, hopelessness-suicidal ideation and worrying in adolescence: concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses. AB - BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders. PMID- 24238953 TI - Living alone, obesity, and smoking increase risk for suicide independently of depressive mood findings from the population-based MONICA/KORA Augsburg cohort study. AB - BACKGROUND: Suicide is strongly associated with mental disorders, particularly with depression. There is insufficient knowledge to what extent sociodemographic and behavioral characteristics contribute to suicide risk. METHODS: A population based cohort study on three independent cross-sectional MONICA/KORA Augsburg surveys with 12,888 subjects (6456 men, 6432 women) was followed up on average for 12.0 years. Information on sociodemographic characteristics, chronic disease conditions, smoking habits, alcohol consumption, depressive symptoms, personality type, and other psychodiagnostic parameters was assessed by standardized interviews. Cox proportional hazards regression analyses were used to compute hazard ratios (HRs) as estimates of relative risks for suicide mortality. Additionally, population-attributable risks were calculated. RESULTS: Within the follow-up period, a total of 1449 persons had died, 38 of them by suicide. Although several variables were associated with increased risk in the basic analyses, only obesity (HR=2.73), smoking (HR=2.23), and living alone (HR=2.19) remained significantly associated with suicide additionally to male sex (HR=3.57) and depressed mood (HR=2.01) in a multivariate analysis. LIMITATIONS: The generalization of our findings to countries with different social, economic or cultural conditions may be questioned. CONCLUSIONS: Our findings extend the knowledge about sociodemographic and behavioral risk factors for suicide in the general population: Suicide prevention measures should not consider only subjects with mental disorders but also address other adverse conditions. PMID- 24238954 TI - Investigation of the marked and long-standing spatial inhomogeneity of the Hungarian suicide rate: a spatial regression approach. AB - BACKGROUND: In the last century Hungary had astonishingly high suicide rates characterized by marked regional within-country inequalities, a spatial pattern which has been quite stable over time. AIMS: To explain the above phenomenon at the level of micro-regions (n=175) in the period between 2005 and 2011. METHODS: Our dependent variable was the age and gender standardized mortality ratio (SMR) for suicide while explanatory variables were factors which are supposed to influence suicide risk, such as measures of religious and political integration, travel time accessibility of psychiatric services, alcohol consumption, unemployment and disability pensionery. When applying the ordinary least squared regression model, the residuals were found to be spatially autocorrelated, which indicates the violation of the assumption on the independence of error terms and accordingly - the necessity of application of a spatial autoregressive (SAR) model to handle this problem. According to our calculations the SARlag model was a better way (versus the SARerr model) of addressing the problem of spatial autocorrelation, furthermore its substantive meaning is more convenient. RESULTS: SMR was significantly associated with the "political integration" variable in a negative and with "lack of religious integration" and "disability pensionery" variables in a positive manner. Associations were not significant for the remaining explanatory variables. LIMITATIONS: Several important psychiatric variables were not available at the level of micro-regions. We conducted our analysis on aggregate data. CONCLUSION: Our results may draw attention to the relevance and abiding validity of the classic Durkheimian suicide risk factors - such as lack of social integration - apropos of the spatial pattern of Hungarian suicides. PMID- 24238955 TI - Epigenetics and depression: return of the repressed. AB - INTRODUCTION: Epigenetics has recently emerged as a potential mechanism by which adverse environmental stimuli can result in persistent changes in gene expression. Epigenetic mechanisms function alongside the DNA sequence to modulate gene expression and ultimately influence protein production. The current review provides an introduction and overview of epigenetics with a particular focus on preclinical and clinical studies relevant to major depressive disorder (MDD). METHODS: PubMed and Web of Science databases were interrogated from January 1995 up to December 2012 using combinations of search terms, including "epigenetic", "microRNA" and "DNA methylation" cross referenced with "depression", "early life stress" and "antidepressant". RESULTS: There is an association between adverse environmental stimuli, such as early life stress, and epigenetic modification of gene expression. Epigenetic changes have been reported in humans with MDD and may serve as biomarkers to improve diagnosis. Antidepressant treatments appear to reverse or initiate compensatory epigenetic alterations that may be relevant to their mechanism of action. LIMITATIONS: As a narrative review, the current report was interpretive and qualitative in nature. CONCLUSION: Epigenetic modification of gene expression provides a mechanism for understanding the link between long term effects of adverse life events and the changes in gene expression that are associated with depression. Although still a developing field, in the future, epigenetic modifications of gene expression may provide novel biomarkers to predict future susceptibility and/or onset of MDD, improve diagnosis, and aid in the development of epigenetics-based therapies for depression. PMID- 24238956 TI - "Every 'never' I ever said came true": transitions from opioid pills to heroin injecting. AB - This qualitative study documents the pathways to injecting heroin by users in Philadelphia and San Francisco before and during a pharmaceutical opioid pill epidemic. Data was collected through in-depth, semi-structured interviews (conducted between 2010 and 2012) that were, conducted against a background of longer-term participant-observation, ethnographic studies of street-based drug users and dealers in Philadelphia (2007-12) and San Francisco (1994-2007, 2012). Philadelphia and San Francisco were selected for their contrasting political economies, immigration patterns and source type of heroin. In Philadelphia the ethnographers found heroin injectors, usually white users, who had started their opiate using careers with prescription opioids rather than transitioning from other drugs. In both Philadelphia and San Francisco, most of the young heroin injectors interviewed began, their drug-use trajectories with opioid pills- usually Percocet (oxycodone and acetaminophen), generic short acting oxycodone or, OxyContin (long-acting oxycodone)--before transitioning to heroin, usually by nasal inhalation (sniffing) or smoking at first, followed by injecting. While most of the Philadelphia users were born in the city or its suburbs and had started using both opioid pills and heroin there, many of the San Francisco users had initiated their pill and sometimes heroin use elsewhere and had migrated to the city from around the country. Nevertheless, patterns of transition of younger injectors were similar in both cities suggesting an evolving national pattern. In contrast, older users in both Philadelphia and San Francisco were more likely to have graduated to heroin injection from non-opiate drugs such as cannabis, methamphetamine and cocaine. Pharmaceutical opioid initiates typically reported switching to heroin for reasons of cost and ease-of-access to supply after becoming physically and emotionally dependent on opioid pills. Many expressed surprise and dismay at their progression to sniffing and subsequently to injecting heroin. Historically and structurally these users found themselves caught at the intersection of two major developments in the opiate supply: (1) an over 500% increase in opiate pill prescription from 1997 to 2005 resulting in easy access to diverted supplies of less stigmatized opiates than heroin and (2) a heroin supply glut, following the US entry of Colombian-sourced, heroin in the early 1990s, that decreased cost and increased purity at the retail level. A nationwide up-cycle of heroin use may be occurring among young inner city, suburban and rural youth fueled by widespread prescription opioid pill use. PMID- 24238957 TI - Timing sequence of multi-planar knee kinematics revealed by physiologic cadaveric simulation of landing: implications for ACL injury mechanism. AB - BACKGROUND: Challenges in accurate, in vivo quantification of multi-planar knee kinematics and relevant timing sequence during high-risk injurious tasks pose challenges in understanding the relative contributions of joint loads in non contact injury mechanisms. Biomechanical testing on human cadaveric tissue, if properly designed, offers a practical means to evaluate joint biomechanics and injury mechanisms. This study seeks to investigate the detailed interactions between tibiofemoral joint multi-planar kinematics and anterior cruciate ligament strain in a cadaveric model of landing using a validated physiologic drop-stand apparatus. METHODS: Sixteen instrumented cadaveric legs, mean 45(SD 7) years (8 female and 8 male) were tested. Event timing sequence, change in tibiofemoral kinematics (position, angular velocity and linear acceleration) and change in anterior cruciate ligament strain were quantified. FINDINGS: The proposed cadaveric model demonstrated similar tibiofemoral kinematics/kinetics as reported measurements obtained from in vivo studies. While knee flexion, anterior tibial translation, knee abduction and increased anterior cruciate ligament strain initiated and reached maximum values almost simultaneously, internal tibial rotation initiated and peaked significantly later (P<0.015 for all comparisons). Further, internal tibial rotation reached mean 1.8(SD 2.5) degrees , almost 63% of its maximum value, at the time that peak anterior cruciate ligament strain occurred, while both anterior tibial translation and knee abduction had already reached their peaks. INTERPRETATION: Together, these findings indicate that although internal tibial rotation contributes to increased anterior cruciate ligament strain, it is secondary to knee abduction and anterior tibial translation in its effect on anterior cruciate ligament strain and potential risk of injury. PMID- 24238958 TI - Cranial humerus translation, deltoid activation, adductor co-activation and rotator cuff disease - different patterns in rotator cuff tears, subacromial impingement and controls. AB - BACKGROUND: Arm adductor co-activation during abduction has been reported as a potential compensation mechanism for a narrow subacromial space in patients with rotator cuff dysfunction. We assessed differences in acromiohumeral distance at rest and the amount of humerus translation during active abduction and adduction in patients with rotator cuff tears (n=20) and impingement (n=30) and controls (n=10), controlled for deltoid, pectoralis major, latissimus dorsi and teres major activation (electromyography). METHODS: During the acquirement of shoulder radiographs, subjects performed standardized isometric arm abduction and adduction tasks. EMG's were normalized between -1 and 1 using the "Activation Ratio", where low values express (pathologic) co-activation, e.g. adductor activation during abduction. FINDINGS: In patients with cuff tears mean rest acromiohumeral distance was 7.6mm (SD=1.6): 3.5mm narrower compared to patients with impingement (95%-CI: 2.4-4.5) and 1.3mm narrower compared to controls (95% CI: -0.1-2.7). Both during abduction and adduction tasks, cranial translation was observed with equal magnitudes for patients and controls, with average values of 2.3 and 1.7mm, respectively. Where patients with cuff tears had lower adductor Activation Ratios (i.e. more adductor co-activation during abduction), no association between abductor/adductor muscle activation and acromiohumeral distance was found. INTERPRETATION: The subacromial space is narrower in patients with rotator cuff tears compared to patients with impingement and controls. We found additional subacromial narrowing during isometric abduction and, to a lesser amount, during adduction in all subjects and more adductor co-activation in patients with cuff tears. We found no association between subacromial space and activation of the deltoid and main adductors. PMID- 24238959 TI - How evidence-based medicine biases physicians against nutrition. AB - Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. PMID- 24238960 TI - Prospective, head-to-head comparison of quantitative coronary angiography, quantitative computed tomography angiography, and intravascular ultrasound for the prediction of hemodynamic significance in intermediate and severe lesions, using fractional flow reserve as reference standard (from the ATLANTA I and II Study). AB - The objective of this study was to compare the diagnostic accuracy of quantitative coronary angiography (QCA), coronary computed tomography angiography (CTA), and intravascular ultrasound (IVUS) with fractional flow reserve (FFR) measurements. Eighty-five lesions (40% to 99% diameter stenosis) in 85 patients were prospectively interrogated by QCA, CTA, IVUS, and FFR. Minimal lumen diameter (MLD), percent diameter stenosis (%DS), minimal lumen area (MLA), and percent area stenosis (%AS) were measured. Correlation, receiver operating characteristic analysis, kappa statistics, and multivariable logistic regression was used to assess relation between anatomic measurements and FFR. Average age was 61.3 +/- 7.8; 62% were men. QCA-derived mean %DS was 55.3% +/- 19.5%; mean FFR 0.81 +/- 0.17; 27% had FFR <=0.75. QCA had the strongest correlation, followed by CTA and then IVUS for MLD (r = 0.67, 0.47, and 0.29, respectively) and for %DS (r = -0.63, -0.52, and -0.22, respectively); QCA-derived MLD had area under the curve of 0.96, with 95% sensitivity and 82% specificity. Cut-point, area under the curve, sensitivity, and specificity for CTA-MLA and IVUS-MLA were 3.11 mm(2), 0.86, 81%, and 81% and 2.68 mm(2), 0.75, 70%, and 80%. In multivariable analysis for each modality, MLD on QCA (odds ratio [OR]: 0.002), %AS on CTA (OR: 1.09) and MLA on IVUS (OR: 0.28) remained independent predictors. In conclusion, in intermediate-to-severe lesions, QCA-, CTA-, and IVUS-derived quantitative anatomic measurements correlated with FFR. CTA-derived cut-points were similar to respective measurements on QCA and IVUS and had similar or better diagnostic performance compared with IVUS. PMID- 24238962 TI - Programmed cell senescence during mammalian embryonic development. AB - Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-beta/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence. PMID- 24238961 TI - Senescence is a developmental mechanism that contributes to embryonic growth and patterning. AB - Senescence is a form of cell-cycle arrest linked to tumor suppression and aging. However, it remains controversial and has not been documented in nonpathologic states. Here we describe senescence as a normal developmental mechanism found throughout the embryo, including the apical ectodermal ridge (AER) and the neural roof plate, two signaling centers in embryonic patterning. Embryonic senescent cells are nonproliferative and share features with oncogene-induced senescence (OIS), including expression of p21, p15, and mediators of the senescence associated secretory phenotype (SASP). Interestingly, mice deficient in p21 have defects in embryonic senescence, AER maintenance, and patterning. Surprisingly, the underlying mesenchyme was identified as a source for senescence instruction in the AER, whereas the ultimate fate of these senescent cells is apoptosis and macrophage-mediated clearance. We propose that senescence is a normal programmed mechanism that plays instructive roles in development, and that OIS is an evolutionarily adapted reactivation of a developmental process. PMID- 24238963 TI - Postsurgical propriospinal myoclonus emerging at wake to sleep transition. PMID- 24238965 TI - Insomnia symptoms, objectively measured sleep, and disease severity in chronic obstructive pulmonary disease outpatients. AB - BACKGROUND: Sleep disturbances are known to have a negative impact on a range of clinical outcomes in chronic obstructive pulmonary disease (COPD). We examined the associations of insomnia symptoms and objectively measured sleep parameters to a composite score for body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index (a multidimensional index of COPD severity), arterial blood gases, nocturnal respiratory disturbances, periodic limb movements (PLM), psychologic distress, pain, age, and sex. METHODS: The sample comprised 73 COPD outpatients (mean age, 63.6years; standard deviation {SD}, 7.5; range 47 85years; 41.1% women). Insomnia symptoms were measured with the Bergen Insomnia Scale (BIS) and sleep efficiency (SE), slow-wave sleep (SWS), and total sleep time (TST) were assessed with clinical polysomnography (PSG). RESULTS: BODE index was positively associated with composite BIS score (P=.040). Patients with more severe COPD presented more complaints of nonrestorative sleep compared to patients with less severe COPD (P=.010). In multivariate analysis, the composite BIS score was independently associated with PLM (P<.001), nocturnal respiratory disturbances (P=.001), pain (P=.031), and psychologic distress (P=.044) but not with the BODE index. Objectively measured sleep variables were not associated with any of the health-related variables. CONCLUSION: Insomnia symptoms in COPD patients result from a wide range of health-related factors. More severe COPD may be associated with a subjective experience of nonrestorative sleep but not with objectively measured sleep variables. PMID- 24238964 TI - Agreement between stroke patients and family members for ascertaining pre-stroke risk for sleep apnea. AB - BACKGROUND: Ascertaining self-reported information about the risk for pre-stroke obstructive sleep apnea (OSA) in the acute stroke period is challenging as many stroke patients have deficits that hinder communication. We examined agreement between stroke patients without communication limitations and family members (proxy) in the pre-stroke risk for OSA. METHODS: Patient-proxy pairs (n=42) were interviewed independently as part of the Brain Attack Surveillance in Corpus Christi (BASIC) Project from May 2010 to April 2011. The Berlin questionnaire was used to measure a high risk for OSA defined as the presence of at least two of the following conditions: (1) snoring behaviors/witnessed apneas, (2) daytime sleepiness, and (3) hypertension or obesity. Patient-proxy agreement was assessed using a kappa coefficient. RESULTS: Forty-three percent of patients self identified as being at high risk for sleep apnea, and 45% of proxies identified patients as high risk. Patient-proxy agreement for high risk for pre-stroke OSA was fair (kappa=0.28) with better agreement for spouses and children proxies (kappa=0.38) than for other family members. Agreement also was fair for most individual questions. CONCLUSIONS: Spouse and child proxy use of the Berlin questionnaire may be an option to assess a patient's pre-stroke likelihood of sleep apnea. Whereas prospective studies of incident stroke in patients with and without objectively confirmed sleep apnea would require formidable resources, our results suggest that an alternative strategy may involve proxy use of the Berlin questionnaire in a retrospective study design. PMID- 24238966 TI - Schizophrenia and antipsychotic medication--better adherence, better outcomes? PMID- 24238967 TI - Desmoplastic fibroma arising in the distal phalanx of the great toe: a case report. AB - Desmoplastic fibroma (DF) of the bone is a rare locally aggressive tumor usually occurring in adolescents and young adults. These tumors most commonly occur in the mandibles and metaphyses of long bones but are extremely rare in small bones, often resulting in diagnostic problems. The occurrence of these tumors in the foot is especially limited. We report the clinical, radiographic, and histologic features of DF arising in the distal phalanx of the great toe and a review of the published data. PMID- 24238968 TI - Midterm results of resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis and the risk factors associated with patient dissatisfaction. AB - We investigated the midterm results of resection arthroplasty of all 5 metatarsal heads in patients with rheumatoid arthritis and forefoot deformity and analyzed the factors that affect patient satisfaction levels. Of 64 patients (1 male, 63 females), 107 feet were treated with resection arthroplasty for forefoot deformity at our hospital from January 1992 to December 2005. The mean follow-up period was 5.8 +/- 3.1 years, with all patients having at least 1 year of follow up. Of the 64 patients, 75% were satisfied with the surgery. The mean score for the postoperative Japanese Society for Surgery of the Foot lesser metatarsophalangeal-interphalangeal scale was 75.0 +/- 15.8 points. Multivariate logistic regression analysis showed that patient-reported dissatisfaction was significantly associated with the recurrence of hammer toe deformity (odds ratio 2.66, 95% confidence interval 1.07 to 6.97), shortening of the resection arthroplasty space (odds ratio 0.85 for a 1-unit increase, 95% confidence interval 0.74 to 0.96), and the recurrence of hallux valgus (odds ratio 1.04 for a 1-unit increase, 95% confidence interval 1.00 to 1.09) during the postoperative period. From our results, interventions to prevent recurrence of hammer toe deformity, especially in toes with preoperative metatarsophalangeal joint dislocations, have been shown to be important in preventing complications and patient dissatisfaction after resection arthroplasty. PMID- 24238969 TI - Implementing the lifelong personal health record in a regionalised health information system: the case of Lombardy, Italy. AB - BACKGROUND: The use of personal health records (PHRs) can help people make better health decisions and improves the quality of care by allowing access to and use of the information needed to communicate effectively with others concerning their health care. OBJECTIVE: This work presents the lifelong PHR system of the Lombardy region as an example of the implementation of an e-health solution that is capable of providing personal clinical documents from a lifelong perspective, integrating different healthcare providers over a large territory. METHODS: The lifelong PHR is embedded in the regional healthcare information system of Lombardy, which is characterised by a large and heterogeneous territory, a large number of different healthcare providers and organisations, and a significant population. RESULTS: The lifelong PHR makes clinical documents available to healthcare professionals and citizens when needed, and it is automatically updated with all of the documents regarding a clinical event regardless of which healthcare provider is currently taking care of the patient. Present statistics show that the lifelong PHR has experienced a wide diffusion in a short period of time, and at the end of 2010, it was active for more than five million Lombardy citizens. Digital reports and e-prescription transactions have almost doubled since 2007 and have reached a coverage of almost 100%. CONCLUSIONS: The qualified and exhaustive collection of patient clinical data and documents should impact daily medical practice, as well as the care pathways and services provided to patients, and should help in the renewal of health assistance and the simplification of patients' access to care. PMID- 24238970 TI - Inter-observer reproducibility of back surface topography parameters allowing assessment of scoliotic thoracic gibbosity and comparison with two standard postures. AB - The objective of this work was to analyze the inter-observer reproducibility of an upright posture designed to bring out the thoracic humps by folding the upper limbs. The effect of this posture on back surface parameters was also compared with two standard radiological postures. A back surface topography was performed on 46 patients (40 girls and 6 boys) with a minimum of 15 degrees Cobb angle on coronal spinal radiographs. Inter-observer reliability was evaluated using the typical error measurement (TEM) and Intraclass Correlation Coefficient (ICC). Variations between postures were assessed using a Student's t test. The inter observer reproducibility is good enough for the three postures. The proposed posture leads to significant changes in the sagittal plane as well as in the identification of thoracic humps. This study shows the reproducibility of the proposed posture in order to explore the thoracic humps and highlights its relevance to explore scoliosis with back surface topography systems. PMID- 24238971 TI - CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer. AB - BACKGROUND: It has been determined that the chemokine receptor CXC receptor 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), regulate several key processes in a wide variety of cancers. In this study, we investigate the possible role of SDF-1 (noncancerous liver tissue) and CXCR4 in liver metastases of colorectal cancer (CRC). MATERIALS AND METHODS: Reverse transcription polymerase chain reaction was performed to examine the expression of SDF-1 in noncancerous liver tissues of 16 CRC patients with liver metastasis and in normal liver tissues of six patients with benign liver disease. We also examined the expression of CXCR4 in cancerous tissues from primary and metastatic tumors. RESULTS: Using reverse transcription-polymerase chain reaction, CXCR4 expression in metastatic tumors tended to be higher than that in primary tumors (P = 0.16). High CXCR4 expression in a primary tumor was found to be related to an increased lymphatic invasion (P = 0.01), an advanced depth of tumor invasion (P = 0.07), and a decrease in the overall survival rate. The SDF-1 expression observed in noncancerous liver tissues of CRC with liver metastasis was significantly higher than that observed in normal liver tissues of benign liver disease (P < 0.05). CONCLUSIONS: In CRC with liver metastasis, CXCR4 expression demonstrated associations with local progression, liver metastasis, and poor overall survival. PMID- 24238972 TI - Aging aggravates long-term renal ischemia-reperfusion injury in a rat model. AB - AIM: Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI. MATERIALS AND METHODS: Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF beta1) and messenger RNA level of TGF-beta1 in the kidney were analyzed. RESULTS: Renal IRI caused significant increases of malondialdehyde and 8 hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-beta1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI. CONCLUSION: Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI. PMID- 24238973 TI - Postconditioning of the small intestine: which is the most effective algorithm in a rat model? AB - BACKGROUND: Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. MATERIALS AND METHODS: Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-alpha, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. RESULTS: The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. CONCLUSIONS: In a rat model of intestinal ischemia reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles. PMID- 24238975 TI - The pelvifemoral rhythm in cam-type femoroacetabular impingement. AB - BACKGROUND: There is growing evidence that femoroacetabular impingement is a potentially important risk factor for the development of early idiopathic osteoarthritis in the nondysplastic hip. Understanding of affected joint kinematics is a basic prerequisite in the evaluation of mechanical disorders in a clinical and research oriented setting. The aim of the present study was to compare pelvifemoral kinematics between subjects diagnosed with femoroacetabular impingement and healthy controls. METHODS: The authors collected motion data of the femur and pelvis on a total of 43 hips - 19 cam impingement hips and 24 healthy controls - using a validated electromagnetic tracking device. The pelvifemoral rhythm in supine position was defined during both active and passive hip flexion and statistically compared between both groups. FINDINGS: A significant increase in posterior pelvic rotation was observed during active hip flexion in the femoroacetabular impingement group compared with the control group (P<0.001). During passive hip flexion, however, posterior pelvic rotation between the impingement group and the controls did not differ significantly (P=0.628). INTERPRETATION: Posterior pelvic rotation during active high-end hip flexion is increased in femoroacetabular impingement, indicating the presence of an active compensational mechanism that decreases the extent of harmful joint conflict during high-flexion activities. PMID- 24238974 TI - Trophic effect of adipose tissue-derived stem cells on porcine islet cells. AB - BACKGROUND: Adipose tissue-derived stem cells (ADSCs), which are widely known as multipotent progenitor cells, release several cytokines that support cell survival and repair. The aim of this study was to investigate whether ADSC secreted molecules could induce a trophic effect in pancreatic islet culture conditions in vitro. MATERIALS AND METHODS: We cocultured porcine islet cells with ADSCs using a transwell system for 48 h and evaluated the viability of islet cells. We also determined the concentration levels of cytokines and insulin in the supernatant of the culture medium. We used anti-vascular endothelial growth factor (VEGF) and anti-interleukin (IL)-6 receptor antibodies to investigate the effect of VEGF and IL-6 on islet cells. RESULTS: ADSCs improved the viability of islet cells in the absence of cell-cell contact (P < 0.05). VEGF and IL-6 levels in the culture medium increased when islet cells were cocultured with ADSCs (P < 0.05). Furthermore, inhibition of VEGF decreased the viability of islet cells (P < 0.05); however, inhibition of IL-6 did not affect islet cell viability. CONCLUSIONS: These results suggested that trophic factors, particularly VEGF, secreted by human ADSCs enhanced the survival and function of porcine islet cells. PMID- 24238976 TI - The effects of prosthetic ankle stiffness on ankle and knee kinematics, prosthetic limb loading, and net metabolic cost of trans-tibial amputee gait. AB - BACKGROUND: Previous studies of commercially-available trans-tibial prosthetic components have been unable to provide clear insight into the relationships between prosthetic mechanical properties and user performance (i.e., gait quality and energy expenditure), the understanding of which is key to improving prosthesis design and prescription. Many of these studies have been limited by not characterising the mechanical properties of the tested prostheses and/or only considered level walking at self-selected speeds. The aim of this study was to conduct a systematic investigation of the effects of ankle rotational stiffness on trans-tibial amputee gait during various walking conditions reflective of those encountered during daily ambulation. METHODS: Ankle and knee kinematics, prosthetic limb normal ground reaction forces, and net metabolic cost were measured in five traumatic unilateral trans-tibial amputees during treadmill walking on the level, a 5% incline and a 5% decline whilst using an experimental articulated prosthetic foot with four different rotational stiffness setups and without changes in alignment between conditions. FINDINGS: Overall, lower dorsiflexion stiffness resulted in greater prosthetic side dorsiflexion motion and sound side knee flexion, reduced normal ground reaction force during the loading phase of prosthetic stance and reduced net metabolic cost. INTERPRETATION: Few differences were observed with changes in plantarflexion stiffness, most likely due to the foot achieving early foot flat. Low dorsiflexion stiffness generally improved gait performance seemingly due to easier tibial progression during stance. However, observed differences were small, suggesting that a wider range of walking and stiffness conditions would be useful to fully explore these effects in future studies. PMID- 24238977 TI - Real-time feedback enhances forward propulsion during walking in old adults. AB - BACKGROUND: Reduced propulsive function during the push-off phase of walking plays a central role in the deterioration of walking ability with age. We used real-time propulsive feedback to test the hypothesis that old adults have an underutilized propulsive reserve available during walking. METHODS: 8 old adults (mean [SD], age: 72.1 [3.9] years) and 11 young adults (age: 21.0 [1.5] years) participated. For our primary aim, old subjects walked: 1) normally, 2) with visual feedback of their peak propulsive ground reaction forces, and 3) with visual feedback of their medial gastrocnemius electromyographic activity during push-off. We asked those subjects to match a target set to 20% and 40% greater propulsive force or push-off muscle activity than normal walking. We tested young subjects walking normally only to provide reference ground reaction force values. FINDINGS: Walking normally, old adults exerted 12.5% smaller peak propulsive forces than young adults (P<0.01). However, old adults significantly increased their propulsive forces and push-off muscle activities when we provided propulsive feedback. Most notably, force feedback elicited propulsive forces that were equal to or 10.5% greater than those of young adults (+20% target, P=0.87; +40% target, P=0.02). With electromyographic feedback, old adults significantly increased their push-off muscle activities but without increasing their propulsive forces. INTERPRETATION: Old adults with propulsive deficits have a considerable and underutilized propulsive reserve available during level walking. Further, real-time propulsive feedback represents a promising therapeutic strategy to improve the forward propulsion of old adults and thus maintain their walking ability and independence. PMID- 24238978 TI - Biomechanical mechanisms of toe-out gait performance in people with and without knee osteoarthritis. AB - BACKGROUND: Toe-out gait modification (increased toe-out angle) has been proposed to decrease medial knee joint loading and slow disease progression in patients with knee osteoarthritis. However, the manner in which toe-out gait modification is performed is unknown. The purposes of this study were to assess the biomechanical strategies of achieving a toe-out gait, and to compare these strategies between older individuals with knee osteoarthritis and young, healthy individuals. METHODS: Lower limb biomechanics were evaluated for ten patients with knee osteoarthritis and for ten young, healthy individuals during treadmill walking. Two trials, consisting of natural gait followed by a ten degree increase in toe-out angle were performed. Transverse plane rotations of the thigh, shank and foot segments were calculated and compared between walking conditions and groups. FINDINGS: External rotation changes with toe-out were significantly different between the thigh and shank, and thigh and foot (P<0.001), but not between the shank and foot (P=0.48). External rotation at each segment was not significantly different (P>0.05) between groups, with the exception of thigh rotation during natural gait (P=0.04). INTERPRETATION: Current findings suggest that increased toe-out gait is primarily achieved through rotation of the shank and foot, with less contribution from the thigh, and those individuals with knee osteoarthritis perform a toe-out gait biomechanically similar to young, healthy individuals. Gait modification programs should address individuals' limitations, such as joint stiffness, to ensure functional performance of toe-out gait modification. PMID- 24238979 TI - 'The midwives aren't allowed to tell you': perceived infant feeding policy restrictions in a formula feeding culture - the Feeding Your Baby Study. AB - OBJECTIVE: to explore the expectations and experiences of postnatal mothers in relation to infant feeding, and to identify how care could be improved. DESIGN: this study used a qualitative, exploratory, descriptive design. Data were collected through one to one in-depth semi-structured interviews and focus groups. SETTING: Tayside area of Eastern Scotland. PARTICIPANTS: seven focus group interviews (n=38 participants) and 40 semi-structured one-to-one interviews with mothers with a range of infant feeding experiences i.e. exclusively breast fed; started breast feeding but changed to formula milk before 16 weeks; exclusively formula fed; or who concurrently breast and formula fed their infant. FINDINGS: a principal theme of 'Mixed and missing messages' emerged, incorporating 'Conflicting advice', 'Information gaps' and 'Pressure to breast feed' with a secondary theme of 'Emotional costs'. Several problems were identified with how women were given information, how infant feeding discussions were held, and the type of support available after the infant is born. KEY CONCLUSIONS: there was a strong perception that some midwives are not 'allowed' to discuss or provide information on formula feeding, and the women reported feeling pressurised to breast feed. Current interpretation of guidance from the UNICEF UK Baby Friendly Initiative may be restricting antenatal discussions about infant feeding. The combination of this partial preparation antenatally and postnatal support that was often inconsistent seems to incur a counter-productive emotional cost. IMPLICATIONS FOR PRACTICE: at strategic, policy and practice levels the infant feeding message needs to change to encourage a more woman centred focus including discussions about the realities of all types of infant feeding. It is important that health providers continue to promote and support breast feeding; and that effective services are provided to women who wish to breast feed to help them to do so. However provision of information about all aspects of feeding is needed as well as support for women who do not wish to breast feed. PMID- 24238980 TI - Realities, difficulties, and outcomes for mothers choosing to breastfeed: primigravid mothers experiences in the early postpartum period (6-8 weeks). AB - OBJECTIVE: to develop an understanding of primiparous women's experiences and challenges of breast feeding in the early postpartum period at two BFI accredited hospitals in the East Midlands in the UK that has lower rates of sustained breast feeding. DESIGN AND SETTING: a hermeneutic or interpretive phenomenology study was conducted across two hospitals in the East Midlands, UK. DATA COLLECTION: 22 primigravid women completed a daily written diary maintained for six weeks post birth. In addition, interviews were conducted with 13 women, nine who had completed a diary and four who did not return a diary but wanted to be interviewed, providing 26 different women's perspectives on their breast feeding experiences either from a diary or interview. FINDINGS: three main themes emerged from the interviews and written diaries: (1) mothers experience a 'roller coaster' of emotions in relation to trying to establish breast feeding, (2) mothers perceive health care professionals as the 'experts' on breast feeding and (3) mothers had difficulties in breast feeding their infants in public, including in front of family and family and when away from their homes. CONCLUSIONS: women were ill prepared for the realities of breast feeding despite their antenatal intention to breast feed. Mothers had a preconceived idea that breast feeding would be 'natural' and without difficulty. When problems occurred, they perceived this to be a breast feeding problem and so choose artificial milk. Mothers require ongoing support to breast feed, especially in the early postpartum period, but more realistic messages about breast feeding need to be included. IMPLICATIONS FOR PRACTICE: there is a clear need for antenatal education to focus on preparing women for the realities of breast feeding, including newborn behaviour, which may affect women's perceptions of breast feeding. Local health care professionals need to draw upon national breast feeding strategies but develop a localised approach in order to address the regional variance. PMID- 24238981 TI - Millennium development goals: all good things must come to an end, so what next? PMID- 24238982 TI - A complementary dual-modality verification for tumor tracking on a gimbaled linac system. AB - BACKGROUND AND PURPOSE: For dynamic tracking of moving tumors, robust intra fraction verification was required, to assure that tumor motion was properly managed during the course of radiotherapy. A dual-modality verification system, consisting of an on-board orthogonal kV and planar MV imaging device, was validated and applied retrospectively to patient data. METHODS AND MATERIALS: Real-time tumor tracking (RTTT) was managed by applying PAN and TILT angular corrections to the therapeutic beam using a gimbaled linac. In this study, orthogonal X-ray imaging and MV EPID fluoroscopy was acquired simultaneously. The tracking beam position was derived from respectively real-time gimbals log files and the detected field outline on EPID. For both imaging modalities, the moving target was localized by detection of an implanted fiducial. The dual-modality tracking verification was validated against a high-precision optical camera in phantom experiments and applied to clinical tracking data from a liver and two lung cancer patients. RESULTS: Both verification modalities showed a high accuracy (<0.3mm) during validation on phantom. Marker detection on EPID was influenced by low image contrast. For the clinical cases, gimbaled tracking showed a 90th percentile error (E90) of 3.45 (liver), 2.44 (lung A) and 3.40 mm (lung B) based on EPID fluoroscopy and good agreement with XR-log file data by an E90 of 3.13, 1.92 and 3.33 mm, respectively, during beam on. CONCLUSION: Dual modality verification was successfully implemented, offering the possibility of detailed reporting on RTTT performance. PMID- 24238984 TI - Treatment of positional plagiocephaly--helmet or no helmet? AB - INTRODUCTION: Positional plagiocephaly has attained widespread attention. There is a lot of data on helmet therapy available, but the natural course of the deformity has not been investigated in depth. The decision for or against helmet therapy can be controversial. This study examined the outcome of both options. METHODS: 128 infants were enrolled in this prospective, non-randomized, longitudinal study. 62 were treated with and 66 without a helmet. The initial cranial vault asymmetry index (modified CVAI) was determined at 6.3 and 6.2 months of age (SD 1.44/2.14). Follow-up took place at the end of helmet therapy (age: 10.2 months, SD 1.77) or after 1 year (age: 18.5 months, SD 2.28) respectively. The outcome and the correlation of the changes to the initial asymmetry were compared. RESULTS: All infants showed a significant reduction of their plagiocephaly. Although children with helmet had more severe asymmetry initially, they showed significantly better improvement (68% vs. 31%). Only a weak correlation was found between the initial asymmetry and the amount of improvement in both groups. CONCLUSION: Despite concerns against helmet therapy (comfort, finances), it should be the treatment of choice for moderate to severe cases. Only mild cases (modified CVAI <= 6.5%) can be adequately treated by conservative, i.e. non-helmet, management. PMID- 24238983 TI - What patients consider important: temporal variations by early and late stage oral, oropharyngeal and laryngeal subsites. AB - Functional outcomes are of high priority to cancer patients and are relevant when considering treatment strategies. This study aimed to collate and analyse importance rankings of UW-QOL over time for patients treated with curative intent for primary head and neck squamous cell carcinoma between 2000 and 2010, and to compare early and late stage oral, oropharyngeal and laryngeal subsites. There were 1614 patients comprising oral cavity 47% (751), oropharyngeal 24% (382), laryngeal 20% (320) and other HNC locations 10% (161). Items of importance remained relatively stable within clinical groups but there were notable differences between groups. For patients with early oral tumours no domain was especially dominant, whereas for late oral tumours swallowing, chewing, speech and saliva were selected more often. Swallowing and saliva were more important in oropharyngeal tumours, as was taste with more advanced oropharyngeal tumours. Speech and activity were important for those with early laryngeal tumours, as were swallowing and speech for more advanced laryngeal tumours. Swallowing and saliva were more important in advanced tumours for all sites. This data confirms the priority patients place on swallowing, chewing, speech, and saliva, therefore curative treatments should optimise these functions wherever possible and provide access to post-treatment interventions as required. PMID- 24238985 TI - Immune characterization of long pentraxin 3 in pigs infected with influenza virus. AB - Long pentraxin 3 (PTX3) is a conserved pattern-recognition secreted protein and a host-defence-related component of the humoral innate immune system. The aim of the present study was to characterize swine PTX3 (SwPTX3) protein expression in influenza virus infected pigs. First, we performed in silico studies to evaluate the cross-reactivity of PTX3 human antibodies against SwPTX3. Secondly, we used in vitro analysis to detect SwPTX3 presence in swine bone marrow dendritic cells (SwBMDC) upon stimulation with different agents by Western blot and immunofluorescence. Finally, the levels of SwPTX3 were assessed in experimental infection of pigs with different strains of influenza virus. This is a novel study where the expression of SwPTX3 was evaluated in the context of a pathogen infection. The initial characterization of SwPTX3 in influenza virus infected pigs contributes to understand the role of PTX proteins in the immune response. PMID- 24238986 TI - Enzyme activities of aerobic lignocellulolytic bacteria isolated from wet tropical forest soils. AB - Lignocellulolytic bacteria have promised to be a fruitful source of new enzymes for next-generation lignocellulosic biofuel production. Puerto Rican tropical forest soils were targeted because the resident microbes decompose biomass quickly and to near-completion. Isolates were initially screened based on growth on cellulose or lignin in minimal media. 75 Isolates were further tested for the following lignocellulolytic enzyme activities: phenol oxidase, peroxidase, beta-d glucosidase, cellobiohydrolase, beta-xylopyranosidase, chitinase, CMCase, and xylanase. Cellulose-derived isolates possessed elevated beta-d-glucosidase, CMCase, and cellobiohydrolase activity but depressed phenol oxidase and peroxidase activity, while the contrary was true of lignin isolates, suggesting that these bacteria are specialized to subsist on cellulose or lignin. Cellobiohydrolase and phenol oxidase activity rates could classify lignin and cellulose isolates with 61% accuracy, which demonstrates the utility of model degradation assays. Based on 16S rRNA gene sequencing, all isolates belonged to phyla dominant in the Puerto Rican soils, Proteobacteria, Firmicutes, and Actinobacteria, suggesting that many dominant taxa are capable of the rapid lignocellulose degradation characteristic of these soils. The isolated genera Aquitalea, Bacillus, Burkholderia, Cupriavidus, Gordonia, and Paenibacillus represent rarely or never before studied lignolytic or cellulolytic species and were undetected by metagenomic analysis of the soils. The study revealed a relationship between phylogeny and lignocellulose-degrading potential, supported by Kruskal-Wallis statistics which showed that enzyme activities of cultivated phyla and genera were different enough to be considered representatives of distinct populations. This can better inform future experiments and enzyme discovery efforts. PMID- 24238987 TI - Pseudomonas aestusnigri sp. nov., isolated from crude oil-contaminated intertidal sand samples after the Prestige oil spill. AB - Strains VGXO14(T) and Vi1 were isolated from the Atlantic intertidal shore from Galicia, Spain, after the Prestige oil spill. Both strains were Gram-negative rod shaped bacteria with one polar inserted flagellum, strictly aerobic, and able to grow at 18-37 degrees C, pH 6-10 and 2-10% NaCl. A preliminary analysis of the 16S rRNA and the partial rpoD gene sequences indicated that these strains belonged to the Pseudomonas genus but were distinct from any known Pseudomonas species. A polyphasic taxonomic approach including phylogenetic, chemotaxonomic, phenotypic and genotypic data confirmed that the strains belonged to the Pseudomonas pertucinogena group. In a multilocus sequence analysis, the similarity of VGXO14(T) and Vi1 to the closest type strain of the group, Pseudomonas pachastrellae, was 90.4%, which was lower than the threshold of 97% established to discriminate species in the Pseudomonas genus. The DNA-DNA hybridisation similarity between strains VGXO14(T) and Vi1 was 79.6%, but below 70% with the type strains in the P. pertucinogena group. Therefore, the strains should be classified within the genus Pseudomonas as a novel species, for which the name Pseudomonas aestusnigri is proposed. The type strain is VGXO14(T) (=CCUG 64165(T)=CECT 8317(T)). PMID- 24238988 TI - Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and soluble guanylyl cyclase alpha and beta subunits in postnatal porcine uteri. AB - The aim of the present study was to investigate the cellular expression and immunolocalization of nitric oxide synthase (NOS) isoforms and soluble guanylyl cyclase (sGC) subunits in postnatal porcine uteri. Immunohistochemical experiments showed that three isoforms of NOS were mainly localized in the uterine luminal and glandular epithelium and myometrium, and the intensity of immunostaining for iNOS and eNOS was increased gradually with temporal development of the postnatal uterus. In addition, sGC subunits, sGCalpha1 and beta, were present in the uterine luminal and glandular epithelium, myometrium and stromal cells. The uterine NOS activity data showed that the total NOS and iNOS activities were significantly increased at postnatal days 21 and 35. Although constitutive NOS activity was increased at postnatal day 21, it decreased subsequently at postnatal day 35. Immunoblot analysis revealed that iNOS protein expression was significantly increased at postnatal days 21 and 35. Furthermore, sGCalpha1 protein expression was not significantly changed throughout days 7 to 35. Collectively, our findings suggest that NO/cGMP signaling is involved in the process of postnatal porcine uterine development. PMID- 24238989 TI - Single administration of butylparaben induces spermatogenic cell apoptosis in prepubertal rats. AB - Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives in foods, cosmetics, toiletries and pharmaceuticals. Some parabens, including butylparaben, exert an estrogenic activity as determined by in vitro estrogen receptor assay and in vivo uterotrophic assay, and adversely affect endocrine secretion and male reproductive function. We conducted a research study to evaluate the acute effects of butylparaben on testicular tissues of prepubertal rats. Three-week-old male rats (n=8) were given a single dose of 1000mg/kg butylparaben. The rats were sacrificed under anesthesia at 3, 6 and 24h after administration, and their testes were collected for histopathological examination. The study revealed progressive detachment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules at 3h, and this effect was enhanced at 6h after administration. Thin seminiferous epithelia and wide tubular lumina were seen at 24h in the butylparaben-treated group, compared to the control. In order to clarify whether sloughed spermatogenic cells underwent apoptosis, TUNEL assay was carried out. We found a significant increase in the number of apoptotic spermatogenic cells in all the treated groups, compared to the controls and a maximal number of apoptotic cells were detected at 6h after administration. In semithin sections, apoptotic cells were easily detected by their prominent basophilia and condensed chromatin, mainly found in spermatocytes. Ultrastructurally, the condensed chromatin and shrunken cytoplasm and nucleus, hallmarks of apoptotic cell death, were observed in butylparaben treated groups. These observations lead us to postulate that butylparaben, similar to other estrogenic compounds, also induces spermatogenic cell apoptosis. PMID- 24238990 TI - Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment. AB - OBJECTIVE: Cerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimer's disease (AD) patients. Here we tested the hypothesis that these two variables could be related. METHODS: We investigated VMR and coherence of resting state EEG rhythms in nine normal elderly (Nold) and in 10 amnesic mild cognitive impairment (MCI) subjects. Resting state eyes-closed EEG data were recorded at baseline pre-CO2 (ambient air, 2 min), during 7% CO2/air mixture inhalation (hypercapnia, 90 s) and post-CO2 (ambient air, 2 min) conditions. Simultaneous frontal bilateral near infrared spectroscopy (NIRS) was performed to assess VMR by cortical oxy- and deoxy-haemoglobin concentration changes. EEG coherence across all electrodes was computed at delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-40 Hz) bands. RESULTS: In Nold subjects, 'total coherence' of EEG across all frequency bands and electrode pairs decreased during hypercapnia, with full recovery during post-CO2. Total coherence resulted lower in pre-CO2 and post-CO2 and presented poor reactivity during CO2 inhalation in MCI patients compared with Nold subjects. Hypercapnia increased oxy-haemoglobin and decreased deoxy-haemoglobin concentrations in both groups. Furthermore, the extent of changes in these variables during CO2 challenge was correlated with the EEG coherence, as a reflection of neurovascular coupling. CONCLUSIONS: Hypercapnia induced normal frontal VMR that was detected by NIRS in both Nold and amnesic MCI groups, while it produced a reactivity of global functional coupling of resting state EEG rhythms only in the Nold group. SIGNIFICANCE: In amnesic MCI patients, global EEG functional coupling is basically low in amplitude and does not react to hypercapnia. PMID- 24238991 TI - Modulation of neck muscle activity induced by intra-oral stimulation in humans. AB - OBJECTIVE: To investigate the effect of painful electrical stimuli applied to intra-oral tissues around the teeth on the neck muscle activity in healthy humans. METHODS: Electromyographic (EMG) responses of the dorsal neck muscles evoked by intra-oral electrical stimulation were recorded before and after local anesthesia to the stimulus site in 17 healthy volunteers. RESULTS: Inhibition of dorsal neck muscle EMG activities on average 80% compared to baseline level was observed with a latency around 50 ms after the electrical stimulation before anesthesia, and the EMG activity inhibition decreased after anesthesia of the intra-oral stimulus site. The perceived intensity of the electrical stimuli as scored on a visual analogue scale (VAS) was 6.1 +/- 0.4 cm before anesthesia and 1.5 +/- 0.2 cm after anesthesia. CONCLUSION: Intra-oral stimulation can inhibit neck muscle activity. This modulation might be attributed mainly to nociceptive afferent nerves however, non-nociceptive fibers could also be responsible. SIGNIFICANCE: Intra-oral information including nociceptive activity can inhibit neck muscle activity. From a clinical viewpoint, the present findings demonstrate the neural connectivity between the trigeminal region and the cervical region raising the possibility that orofacial pain conditions could influence head, neck and shoulder activity. PMID- 24238992 TI - Cardiac myxoma with glandular elements: a clinicopathological and immunohistochemical study of five new cases with an emphasis on differential diagnosis. AB - This paper reported five new cases of cardiac myxoma with glandular components, known as glandular cardiac myxoma. The goals of this study were to analyze the clinicopathological features of this disease and to explore new features for differential diagnosis. The patient series included three women and two men. All tumors were located in the left atrium without invasion of the adjacent myocardium. Patients presented with cardiac-related or embolization symptoms. Histologically, neoplasms consisted of well-formed glandular structures and typical myxoma areas. No nuclear atypia, mitosis, or necrosis was identified in the glandular structures. Glandular lining cells were strongly positive for pan cytokeratin, epithelial membrane antigen, CAM5.2 and cytokeratin 7, but were negative for some organ-specific markers, such as thyroid transcription factor-1, calretinin, estrogen receptor, progesterone receptor, gross cystic disease fluid protein, prostate-specific antigen, prostate-specific acid phosphatase, cytokeratin 20 and caudal type homeobox 2. In conclusion, glandular cardiac myxoma is a rare disease which shows characteristics similar to those of classical cardiac myxoma. Because of its rarity, glandular cardiac myxoma must be distinguished from adenocarcinoma metastatic to the heart. The combination of histopathological features and immunohistochemical profiles should improve the diagnostic accuracy of glandular cardiac myxoma. PMID- 24238993 TI - Analysis of the combustion and pyrolysis of dried sewage sludge by TGA and MS. AB - In this study, the combustion and pyrolysis processes of three sewage sludge were investigated. The sewage sludge came from three wastewater treatment plants. Proximate and ultimate analyses were performed. The thermal behaviour of studied sewage sludge was investigated by thermogravimetric analysis with mass spectrometry (TGA-MS). The samples were heated from ambient temperature to 800 degrees C at a constant rate 10 degrees C/min in air (combustion process) and argon flows (pyrolysis process). The thermal profiles presented in form of TG/DTG curves were comparable for studied sludges. All TG/DTG curves were divided into three stages. The main decomposition of sewage sludge during the combustion process took place in the range 180-580 degrees C with c.a. 70% mass loss. The pyrolysis process occurred in lower temperature but with less mass loss. The evolved gaseous products (H2, CH4, CO2, H2O) from the decomposition of sewage sludge were identified on-line. PMID- 24238994 TI - The use of agricultural substrates to improve methane yield in anaerobic co digestion with pig slurry: effect of substrate type and inclusion level. AB - Anaerobic co-digestion of pig slurry with four agricultural substrates (tomato, pepper, persimmon and peach) was investigated. Each agricultural substrate was tested in co-digestion with pig slurry at four inclusion levels: 0%, 15%, 30% and 50%. Inclusion levels consisted in the replacement of the volatile solids (VS) from the pig slurry with the VS from the agricultural substrate. The effect of substrate type and inclusion level on the biochemical methane potential (BMP) was evaluated in a batch assay performed at 35 degrees C for 100 days. Agricultural substrate's chemical composition was also analyzed and related with BMP. Additionally, Bacteria and Archaea domains together with the four main methanogenic archaeal orders were quantified using quantitative real-time TaqMan polymerase chain reaction (qPCR) at the end of the experiment to determine the influence of agricultural substrate on sludge's microbial composition. Results showed that vegetable substrates (pepper and tomato) had higher lipid and protein content and lower carbohydrates than fruit substrates (persimmon and peach). Among substrates, vegetable substrates showed higher BMP than fruit substrates. Higher BMP values were obtained with increasing addition of agricultural substrate. The replacement of 50% of VS from pig slurry by tomato and pepper increased BMP in 41% and 44%, respectively compared with pig slurry only. Lower increments in BMP were achieved with lower inclusion levels. Results from qPCR showed that total bacteria and total archaea gene concentrations were similar in all combinations tested. Methanomicrobiales gene concentrations dominated over the rest of individual archaeal orders. PMID- 24238995 TI - Thyroglossal duct papillary carcinoma in a 15-year old female and review of pediatric cases of thyroglossal duct carcinoma. AB - Thyroglossal duct carcinoma is rare, occurring in approximately 1% of thyroglossal duct cysts. Excluding this case report there have been 25 cases of adolescent thyroglossal duct carcinoma reported in the English literature thus far. Most of the pathology reported has been papillary or follicular carcinoma, leading to the question of whether or not to perform concurrent thyroidectomy. Based on our review of the pediatric cases of thyroglossal duct carcinoma we elected not to perform a concurrent thyroidectomy and recommend close follow-up to monitor for signs of future thyroid involvement. PMID- 24238996 TI - Immunolocalization of Smurf1 in Hirano bodies. AB - The Smad ubiquitination regulatory factor 1 (Smurf1) is one of the E3 ubiquitin ligases and is related to multiple biological processes. Despite the various roles played by this protein, there is no report on the function of Smurf1 in neurodegeneration. Hirano bodies (HBs) are intracellular structures within neuronal processes and were first described in the hippocampus of individuals with amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam. In addition, the number of HBs increases in the brains of patients with Alzheimer's disease (AD) compared with age-matched non-demented control individuals. In this study, we immunohistochemically demonstrated that Smurf1 localized in HBs in the brains of patients with AD by using plural anti-Smurf1 antibodies, and Smurf1 co-localized with HBs marker proteins by using confocal microscopy. Moreover, we demonstrated that Smurf1 localized in HB-like F-actin aggregates in a cell culture system via treatment with the actin-stabilizing toxin jasplakinolide (jpk). Smurf1 represents a novel protein component of HBs, to be included in an expanding list of HB-associated proteins. PMID- 24238997 TI - Abdominal paresthesia resembling restless legs syndrome successfully treated with iron supplement therapy: a case report. PMID- 24238998 TI - Contribution of cerebral vasospasm to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. PMID- 24238999 TI - Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model. AB - Interleukin 17A (IL-17A) is a cytokine linked to inflammatory bowel disease. We investigated IL-17A expression in human colonic mucosa, whether IL-17A can elicit colonic mucosal damage in a human explant model and modulate gastrointestinal epithelial permeability in cell culture. We also tested if select cannabinoid ligands, shown to be protective in colitis models could attenuate damage caused by IL-17A. In addition, the ability of pro-inflammatory cytokines TNF-alpha and IL-1beta to modulate levels of IL-17A in the explant colitis model was also explored. IL-17A incubation caused significant mucosal epithelial and crypt damage which were attenuated following hydrocortisone treatment, and also reduced following anandamide or cannabidiol incubation. IL-17A-evoked mucosal damage was also associated with an increase in matrix metalloprotease activity. However, IL 17A did not induce any significant changes in epithelial permeability in confluent Caco-2 cell monolayers over a 48h incubation period. IL-17A was located predominantly in human mucosal epithelium together with IL-17C, but both IL-17A and IL-17C were also expressed in the lamina propria and submucosa. Incubation of human colonic mucosal tissue or Caco-2 cells with pro-inflammatory cytokines TNF alpha and IL-1beta however did not alter IL-17A expression. These results indicate IL-17A has a widespread distribution in the human colon and the capacity to elicit mucosal damage which can be attenuated by cannabinoid ligands. PMID- 24239000 TI - How effective are public health departments at preventing mortality? AB - This study estimates the causal impact of variation in the expenditures of California county departments of public health on all-cause mortality rates and the associated value of lives saved. Since the activities of county departments of public health are likely to affect mortality rates with a lag, Koyck distributed lag models are estimated using the Lewbel instrumental variables estimator. The findings show that an additional $10 per capita of public health expenditures reduces all-cause mortality by 9.1 deaths per 100,000. At current funding levels, the long-run annual number of lives saved by the presence of county departments of public health in California is estimated to be approximately 27,000 (26,937 lives, 95% confidence interval: [11,963, 41,911]). The annual value of these lives is estimated to be worth $212.8 billion using inflation-adjusted standard U.S. government estimates of the value of a statistical life ($7.9 million). PMID- 24239001 TI - Putting together "Shattered Dreams": a program to reduce alcohol-related and distracted driving-related car crashes among adolescents. PMID- 24239002 TI - Chromogranin A is a T cell antigen in human type 1 diabetes. AB - Chromogranin A (ChgA) is a beta cell secretory granule protein and a peptide of ChgA, WE14, was recently identified as a ligand for diabetogenic CD4 T cell clones derived from the NOD mouse. In this study we compared responses of human CD4 T cells from recent onset type 1 diabetic (T1D) and control subjects to WE14 and to an enzymatically modified version of this peptide. T cell responders to antigens were detected in PBMCs from study subjects by an indirect CD4 ELISPOT assay for IFN-gamma. T1D patients (n = 27) were recent onset patients within one year of diagnosis, typed for HLA-DQ8. Controls (n = 31) were either 1st degree relatives with no antibodies or from the HLA-matched general population cohort of DAISY/TEDDY. A second cohort of patients (n = 11) and control subjects (n = 11) was tested at lower peptide concentrations. We found that WE14 is recognized by T cells from diabetic subjects vs. controls in a dose dependent manner. Treatment of WE14 with transglutaminase increased reactivity to the peptide in some patients. This work suggests that ChgA is an important target antigen in human T1D subjects and that post-translational modification may play a role in its reactivity and relationship to disease. PMID- 24239004 TI - Characterization of craniofacial sutures using the finite element method. AB - Characterizing the biomechanical behavior of sutures in the human craniofacial skeleton (CFS) is essential to understand the global impact of these articulations on load transmission, but is challenging due to the complexity of their interdigitated morphology, the multidirectional loading they are exposed to and the lack of well-defined suture material properties. This study aimed to quantify the impact of morphological features, direction of loading and suture material properties on the mechanical behavior of sutures and surrounding bone in the CFS. Thirty-six idealized finite element (FE) models were developed. One additional specimen-specific FE model was developed based on the morphology obtained from a uCT scan to represent the morphological complexity inherent in CFS sutures. Outcome variables of strain energy (SE) and von Mises stress (sigmavm) were evaluated to characterize the sutures' biomechanical behavior. Loading direction was found to impact the relationship between SE and interdigitation index and yielded varied patterns of sigmavm in both the suture and surrounding bone. Adding bone connectivity reduced suture strain energy and altered the sigmavm distribution. Incorporating transversely isotropic material properties was found to reduce SE, but had little impact on stress patterns. High resolution uCT scanning of the suture revealed a complex morphology with areas of high and low interdigitations. The specimen specific suture model results were reflective of SE absorption and sigmavm distribution patterns consistent with the simplified FE results. Suture mechanical behavior is impacted by morphologic factors (interdigitation and connectivity), which may be optimized for regional loading within the CFS. PMID- 24239003 TI - Low-molecular-weight heparin for anti-coagulation after left ventricular assist device implantation. AB - BACKGROUND: Anti-coagulation is required in patients with left ventricular assist devices (LVADs). We evaluated the feasibility of low-molecular-weight heparin (LMWH) for initiation of anti-coagulation and transitioning to oral anti coagulation after LVAD implantation. METHODS: This single-center study included 78 consecutive patients who underwent either Thoratec HeartMate II LVAD (n = 27) or HeartWare ventricular assist device (HVAD, n = 51) implantation. The LMWHs enoxaparin (n = 50) and dalteparin (n = 28) were used. LMWH was started within 24 hours post-operatively in 79.5% of patients. No anti-coagulation was given before starting LMWH therapy. LMWH activity was monitored by determination of anti factor Xa levels in plasma. RESULTS: The majority of patients (80.7%) had peak anti-Xa activity within the defined range of efficacy of 0.2 to 0.4 IU/ml by the second day of treatment. Mean effective peak anti-Xa activity was 0.28 +/- 0.06 IU/ml. Mean duration of anti-coagulation with LMWH was 25.8 +/- 18 days. Ischemic strokes were observed in 3 patients (3.8%), with a total of 4 events. Three events occurred while on LMWH, and 1 event occurred during follow-up on oral anti coagulation. There was 1 fatal stroke. No pump thrombus was observed. Major bleeding was observed in 5 patients (6.4%), with a total of 6 events. Gastrointestinal bleeding was the most common complication (n = 3). There were no fatal bleeding events. CONCLUSIONS: LMWH in the setting of LVAD shows rapid and constant biologic efficacy. Anti-coagulation with LMWH appears feasible after LVAD implantation. These findings support further evaluation of LMWH as an alternative to unfractionated heparin in this patient cohort. PMID- 24239005 TI - Functional properties of bone marrow-derived MSC-based engineered cartilage are unstable with very long-term in vitro culture. AB - The success of stem cell-based cartilage repair requires that the regenerate tissue reach a stable state. To investigate the long-term stability of tissue engineered cartilage constructs, we assessed the development of compressive mechanical properties of chondrocyte and mesenchymal stem cell (MSC)-laden three dimensional agarose constructs cultured in a well defined chondrogenic in vitro environment through 112 days. Consistent with previous reports, in the presence of TGF-beta, chondrocytes outperformed MSCs through day 56, under both free swelling and dynamic culture conditions, with MSC-laden constructs reaching a plateau in mechanical properties between days 28 and 56. Extending cultures through day 112 revealed that MSCs did not simply experience a lag in chondrogenesis, but rather that construct mechanical properties never matched those of chondrocyte-laden constructs. After 56 days, MSC-laden constructs underwent a marked reversal in their growth trajectory, with significant declines in glycosaminoglycan content and mechanical properties. Quantification of viability showed marked differences in cell health between chondrocytes and MSCs throughout the culture period, with MSC-laden construct cell viability falling to very low levels at these extended time points. These results were not dependent on the material environment, as similar findings were observed in a photocrosslinkable hyaluronic acid (HA) hydrogel system that is highly supportive of MSC chondrogenesis. These data suggest that, even within a controlled in vitro environment that is conducive to chondrogenesis, there may be an innate instability in the MSC phenotype that is independent of scaffold composition, and may ultimately limit their application in functional cartilage repair. PMID- 24239006 TI - Open questions in lipid droplet biology. AB - Lipid droplets (LDs) have been the focus of intense research for the past decade because of their active engagement in lipid metabolism and relationship with diseases. In contrast to other intracellular organelles, LDs are composed of a mass of hydrophobic lipid esters that is covered with a phospholipid monolayer. The unique architecture makes the LD a formidable object to study by the methods available today, and many fundamental questions remain unanswered. This review focuses on some of those questions, such as how LDs form and grow, how proteins move to and from LDs, and how LDs are related to protein degradation; we will also discuss what is not known about LDs. We think that small LDs that have thus far eluded analysis are the key to resolving many of the above-mentioned questions. PMID- 24239007 TI - The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2 alkylquinolines derive from fatty acids, not 3-ketofatty acids. AB - Groups of pathogenic bacteria use diffusible signals to regulate their virulence in a concerted manner. Pseudomonas aeruginosa uses 4-hydroxy-2-alkylquinolines (HAQs), including 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2 heptylquinoline (PQS), as unique signals. We demonstrate that octanoic acid is directly incorporated into HHQ. This finding rules out the long-standing hypothesis that 3-ketofatty acids are the precursors of HAQs. We found that HAQ biosynthesis, which requires the PqsABCD enzymes, proceeds by a two-step pathway: (1) PqsD mediates the synthesis of 2-aminobenzoylacetate (2-ABA) from anthraniloyl-coenzyme A (CoA) and malonyl-CoA, then (2) the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ, the direct precursor of PQS. PqsB is tightly associated with PqsC and required for the second step. This finding uncovers promising targets for the development of specific antivirulence drugs to combat this opportunistic pathogen. PMID- 24239009 TI - Catalytic mechanism of stereospecific formation of cis-configured prenylated pyrroloindoline diketopiperazines by indole prenyltransferases. AB - Indole prenyltransferases AnaPT, CdpC3PT, and CdpNPT are known to catalyze the formation of prenylated pyrroloindoline diketopiperazines from tryptophan containing cyclic dipeptides in one-step reactions. In this study, we investigated the different stereoselectivities of these enzymes toward all the stereoisomers of cyclo-Trp-Ala and cyclo-Trp-Pro. The stereoselectivities of AnaPT and CdpC3PT mainly depend on the configuration of the tryptophanyl moiety in the substrates, and they usually introduce the prenyl moiety from the opposite sides. CdpNPT showed lower stereoselectivity, and the structure of the second amino acid moiety in the substrates is important for the stereospecificity in its enzyme catalysis. Moreover, we determined the crystal structure of AnaPT in complex with thiolodiphosphate and compared it with the known structures of CdpNPT. Our results clearly revealed the presence of an indole binding mode that has so far not been characterized. PMID- 24239008 TI - Identification of an allosteric pocket on human hsp70 reveals a mode of inhibition of this therapeutically important protein. AB - Hsp70s are important cancer chaperones that act upstream of Hsp90 and exhibit independent anti-apoptotic activities. To develop chemical tools for the study of human Hsp70, we developed a homology model that unveils a previously unknown allosteric site located in the nucleotide binding domain of Hsp70. Combining structure-based design and phenotypic testing, we discovered a previously unknown inhibitor of this site, YK5. In cancer cells, this compound is a potent and selective binder of the cytosolic but not the organellar human Hsp70s and has biological activity partly by interfering with the formation of active oncogenic Hsp70/Hsp90/client protein complexes. YK5 is a small molecule inhibitor rationally designed to interact with an allosteric pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70. PMID- 24239010 TI - The neural basis for writing from dictation in the temporoparietal cortex. AB - Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region. PMID- 24239011 TI - Incentivising reproducible research. PMID- 24239012 TI - Toll-like receptor 4 gene polymorphisms and acute coronary syndrome: no association in a Mexican population. AB - OBJECTIVE: The objective of this study was to establish the role of the TLR-4 gene polymorphisms in individuals in risk of developing ACS. METHODS: The study included 457 Mexican patients with ACS and 283 control individuals. The TLR-4 Asp299Gly and TLR-4 Thr399Ile single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays on an 7900HT Fast real-time PCR system according to manufacturer's instructions (Applied Biosystems, Foster City, USA). RESULTS: The results obtained in this study showed that the frequency of the two polymorphisms (TLR-4 Asp299Gly and TLR-4 Thr399Ile) studied were similar between patients with ACS and healthy controls. Multiple logistic regression analysis showed that the largest risk factor for ACS development was given by smoking (11.88-fold increased risk), hypertension (4.32-fold increased risk), type II diabetes (3.44-fold increased risk), gender (2.32-fold increased risk), and dyslipidemia (1.52-fold increased risk). CONCLUSION: The Asp299Gly and Thr399Ile polymorphisms were not associated with susceptibility to ACS in the Mexican population. PMID- 24239013 TI - The economic value of enteral medical nutrition in the management of disease related malnutrition: a systematic review. AB - Economic evaluations for medical nutrition, such as oral nutritional supplements (ONS), are relatively uncommon compared with other health technologies, and represent an area that has not been reviewed so far. In this systematic review, economic evaluations of enteral medical nutrition in the management of disease related malnutrition (DRM) were reviewed and qualified to estimate the economic value. Initially, 481 studies were found, of which 37 full-text articles were assessed for eligibility and were rated on their quality using the Quality of Health Economic Studies (QHES) instrument. The final review focused on the high QHES quality economic evaluation studies. As both the studied medical nutrition intervention and the form of the economic evaluation varied, a quantitative synthesis (meta-analysis) was not attempted but a critical analysis and comparison of the individual study results were performed. ONS was the most studied intervention, covering several patient populations and different health care settings. Outcomes included cost savings (n = 3), no significant extra costs per unit of clinical and/or functional improvement (n = 1), or significantly higher costs per unit of clinical and/or functional improvement but still cost effective for the used threshold (n = 4). This review shows that the use of enteral medical nutrition in the management of DRM can be efficient from a health economic perspective. PMID- 24239014 TI - Infection prevention and control standards in assisted living facilities: are residents' needs being met? AB - BACKGROUND: Assisted living facilities (ALFs) provide housing and care to persons unable to live independently, and who often have increasing medical needs. Disease outbreaks illustrate challenges of maintaining adequate resident protections in these facilities. OBJECTIVES: Describe current state laws on assisted living admissions criteria, medical oversight, medication administration, vaccination requirements, and standards for infection control training. METHODS: We abstracted laws and regulations governing assisted living facilities for the 50 states using a structured abstraction tool. Selected characteristics were compared according to the time period in which the regulation took effect. Selected state health departments were queried regarding outbreaks identified in assisted living facilities. RESULTS: Of the 50 states, 84% specify health-based admissions criteria to assisted living facilities; 60% require licensed health care professionals to oversee medical care; 88% specifically allow subcontracting with outside entities to provide routine medical services onsite; 64% address medication administration by assisted living facility staff; 54% specify requirements for some form of initial infection control training for all staff; 50% require reporting of disease outbreaks to the health department; 18% specify requirements to offer or require vaccines to staff; 30% specify requirements to offer or require vaccines to residents. Twelve states identified approximately 1600 outbreaks from 2010 to 2013, with influenza or norovirus infections predominating. CONCLUSIONS: There is wide variation in how assisted living facilities are regulated in the United States. States may wish to consider regulatory changes that ensure safe health care delivery, and minimize risks of infections, outbreaks of disease, and other forms of harm among assisted living residents. PMID- 24239015 TI - Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives. AB - We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti MRSA activity). The structure-activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A-B benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity. PMID- 24239016 TI - Synthesis and antitumor-evaluation of 1,3-selenazole-containing 1,3,4-thiadiazole derivatives. AB - A series of novel 1,3-selenazole-containing 1,3,4-thiadiazole derivatives bearing Schiff base moieties were synthesized and evaluated for their in vitro antiproliferative activities against human breast cancer cell MCF-7 and mouse lymphocyte leukemia cell L1210 by CCK-8 assay. The majority of the compounds showed better activity against MCF-7 cell, compared with lead compound PCS. In particular, compound 6c was the most potent compound with IC50 value of 4.02 MUM. PMID- 24239017 TI - Design, synthesis and biological evaluation of alpha-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors. AB - The discovery and optimisation of a new class of benzothiazole small molecules that inhibit bacterial DNA gyrase and topoisomerase IV are described. Antibacterial properties have been demonstrated by activity against DNA gyrase ATPase and potent activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Haemophilus influenzae. Further refinements to the scaffold designed to enhance drug-likeness included analogues bearing an alpha substituent to the carboxylic acid group, resulting in excellent solubility and favourable pharmacokinetic properties. PMID- 24239018 TI - Comprehending renin inhibitor's binding affinity using structure-based approaches. AB - The performance of several structure-based design (SBD) approaches in predicting the binding affinity of diverse small molecule inhibitors co-crystallized to human renin was assessed to ascertain the modeling tool and method of choice required when dealing with structure-based lead optimization projects. Most of the SBD approaches investigated here were able to provide qualitative guidance, but quantitative accuracy as well as decisive discrimination between [in]actives is still not within reach. Such an outcome suggests that the current methods need improvement to capture the overall physics of the binding phenomenon for consistent applications in a lead optimization setting. PMID- 24239019 TI - Arteriovenous fistula survival and needling technique: long-term results from a randomized buttonhole trial. AB - BACKGROUND: We previously have shown that buttonhole needling is associated with a reduction in hematoma and postulated that buttonhole needling may increase long term survival of an arteriovenous fistula (AVF). The purpose of this study was to evaluate AVF survival and complications in buttonhole versus standard needling. STUDY DESIGN: Long-term follow up of a randomized controlled trial in which participants were randomly assigned to standard or buttonhole needling and followed up until the AVF was abandoned or the study end date. SETTING & PARTICIPANTS: 140 long-term hemodialysis patients in Calgary, Alberta. INTERVENTION: Buttonhole needling with median time of exposure to the intervention of 13.2 (IQR, 7.8-19.4) months. OUTCOMES & MEASUREMENTS: Patients were prospectively followed up for study outcomes. Median follow-up times were 17.2 (IQR, 11.9-37.8) and 19.2 (IQR, 12.5-41.0) months for standard and buttonhole needling, respectively (P=0.2). The primary outcome was median access survival in months. Other outcomes included assisted and unassisted patency rates, rates of surgical and radiologic interventions, and time to abandonment (months) of buttonhole. RESULTS: Baseline characteristics were similar. The primary outcome, median access survival, was similar in both groups: 16.0 (IQR, 10.6-29.3) and 18.4 (IQR, 10.9-32.7) months for standard and buttonhole needling, respectively (P=0.2). There were 7 (10.1%) and 6 (8.6%) thromboses with standard and buttonhole needling, respectively (P=0.6). Median fistulogram rates were similar between techniques (P=0.2 with intention-to-treat analysis). Most patients (46 of 70) abandoned buttonhole needling by a median of 11.3 (IQR, 4.8 18.2) months. Median time to first infection for buttonhole needling was 11.1 (IQR, 4.9-30.0) months. There were no infections in standard needling of AVFs. LIMITATIONS: Findings are limited to patients needled by multiple hemodialysis nurses and not applicable to self-needlers. CONCLUSIONS: AVFs with buttonhole needling did not have improved survival. The lack of survival benefit and higher risk of infection should be noted when promoting buttonhole needling. PMID- 24239020 TI - Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research. AB - Identification of disease-related genes is a critical step in understanding the molecular basis of disease and developing targeted therapies. The genetic study of diseases occurring in the offspring of consanguineous unions is a powerful way to discover new disease genes. Pediatric nephrology provides an excellent example because ~70% of cases of kidney disease in childhood are congenital with a likely genetic basis. This percentage is likely to be even higher in countries with a high consanguinity rate, such as the Kingdom of Saudi Arabia. However, there are a number of challenges, such as cultural, legal, and religious restrictions, that should be appreciated before carrying out genetic research in a tradition-bound country. In this article, we discuss the background, opportunities, and challenges involved with this unique opportunity to conduct studies of such genetic disorders. Keys to success include collaboration and an understanding of local traditions and laws. PMID- 24239022 TI - Respiratory outcomes for the tiniest or most immature infants. AB - Extremely low birth weight (<1000 g birth weight) or extremely preterm (<28 weeks of gestation) infants are surviving in greater numbers as neonatal care advances. Many of these survivors, especially those who develop bronchopulmonary dysplasia, have more respiratory ill health in the first years after discharge home, reduced respiratory function and impaired exercise capacity throughout childhood and into adulthood compared with term-born controls. It is important to establish the long term respiratory outcomes for the tiniest or most immature survivors as they grow older, since they may contribute disproportionately to rates of chronic obstructive pulmonary disease and respiratory ill-health in adulthood. PMID- 24239021 TI - Guidelines to decrease unanticipated hospital admission following adenotonsillectomy in the pediatric population. AB - INTRODUCTION: Tonsillectomy has become one of the most commonly performed surgical procedures in the pediatric-aged patient. Many of these children are diagnosed with obstructive sleep apnea (OSA). Although polysomnography is considered the gold standard, many practioners rely on the clinical examination and parental history. Nationwide Children's Hospital recently instituted pediatric adenotonsillectomy guidelines for hospital admission to help determine which patients should be done in main hospital OR vs. outpatient surgery facility. The main goal was to decrease unanticipated admissions. The secondary goal was to determine areas for practice improvement. METHODS: Using databases for the hospital, operating room, and otolaryngology, all cases with CPT codes 42820, 42830, 42825, 42826, and 42821 were evaluated from October 2009 to August 2012 in the main operating room and 2 outpatient surgery centers. Data for each unanticipated admission were reviewed to determine whether the criteria were met according to the developed guidelines. Fisher's exact test was applied to the unplanned admission rate before and after the institution of the guidelines. Non paired t-test and a Fisher's exact test were used for comparison of the demographic data between the two groups. RESULTS: Following the institution of the pediatric adenotonsillectomy guidelines, the number of unanticipated admissions decreased from an absolute number of 88 to 43. This represents a decrease from 2.38% to 1.44% (p=0.008). Forty-two percent of the unanticipated admissions prior to establishing guidelines were in patients who would have met criteria for admission based on the guidelines. This decreased to 30% after establishing the guidelines. CONCLUSION: We found that the institution of pediatric adenotonsillectomy guidelines for patients undergoing adenotonsillectomy significantly decreased the rate of unanticipated admission. However, there was still a significant percentage (30%) of unanticipated admissions due to non-compliance with the guidelines demonstrating the need for ongoing practice improvement. PMID- 24239023 TI - Kinematics and muscle activity of the head, lumbar and knee joints during 180 degrees turning and sitting down task in older adults. AB - BACKGROUND: The "180 degrees turning and sitting down task" is a very conscious movement that requires focusing on turning at the exact moment, and very few studies address on this topic in older adults. The purpose of the study was to compare kinematics and electromyography of the head, lumbar and knee joints during 180 degrees turning in older and young adults. METHODS: Twenty older adults and 20 younger adults were assessed. A 16-channel telemetry electromyography system with electrogoniometers and an inclinometer were used to record the head, lumbar and knee joint kinematic and electromyography data during the 180 degrees turning. This movement had been further divided into 4 phases (braking, mid-stance, swing, and terminal loading) for analysis. FINDINGS: There were significant differences in the joint displacement and muscular activity among the different phases. Comparison between groups showed that the older adults group had less lateral lumbar flexion, less knee flexion and lower velocity of the head and knee flexion compared to young adults during turning. The electromyography data of the left biceps femoris, left gastrocnemius and left erector spinae muscles in the older adults group showed significantly higher levels than in the young adults. INTERPRETATION: Older adults need to adjust velocities of moving joints and increase the extensor synergy muscles of the back and the stance leg to provide posture stability. Kinematics and neuromuscular modulations of the head, lumbar and knee are required according to the various phases of the turn movements and change with aging. PMID- 24239024 TI - Biomechanical comparison of a two-level anterior discectomy and a one-level corpectomy, combined with fusion and anterior plate reconstruction in the cervical spine. AB - BACKGROUND: Common fusion techniques for cervical degenerative diseases include two-level anterior discectomy and fusion and one-level corpectomy and fusion. The aim of the study was to compare via in-vitro biomechanical testing the effects of a two-level anterior discectomy and fusion and a one-level corpectomy and fusion, with anterior plate reconstruction. METHODS: Seven fresh frozen human cadaveric spines (C3-T1) were dissected from posterior musculature, preserving the integrity of ligaments and intervertebral discs. Initial biomechanical testing consisted of no-axial preload and 2Nm in flexion-extension, lateral bending and axial rotation. Thereafter, discectomies were performed at C4-5 and C5-6 levels, then two interbody cages and an anterior C4-C5-C6 plate was implanted. The flexibility tests were repeated and followed by C5 corpectomy and C4-C6 plate reconstruction. Biomechanical testing was performed again and statistical comparisons among the means of range of motion and axial rotation energy loss were investigated. FINDINGS: The two-level cage-plate construct had significantly lower range of motion than the one-level corpectomy-plate construct (P<=0.03). Axial rotation energy loss was significantly (P<=0.03) greater for the corpectomy plate construct than for the two-level cage-plate construct and the intact condition. INTERPRETATION: A two-level cage-plate construct provides greater stability in flexion, extension and lateral bending motions when compared to a one-level corpectomy-plate construct. A two-level cage-plate is more likely to maintain axial balance by reducing the energy lost in axial rotation. PMID- 24239025 TI - Evaluation of microbial diversity in sulfite-added and sulfite-free wine by culture-dependent and -independent methods. AB - The difference in microbiota including non-lactic acid bacteria, non-acetic acid bacteria, and wild yeast during winemaking and in the end-products between sulfite-added and sulfite-free wine, was investigated using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and a culture dependent method. There were differences between the microorganisms detected by PCR-DGGE and those detected by the culture-dependent method, probably because of the selectivity of culture medium and the characteristics of PCR-based method. In both the red wine and white wine, the microbial diversity of the sulfite-added wine was lower than that of the sulfite-free wine during fermentation. Tatumella terrea was detected from the fermenting must by PCR-DGGE and by the culture dependent method, even though sulfite inhibited its growth to some extent. We confirmed that the addition of sulfite plays an important role in winemaking by inhibiting the growth of unexpected microorganisms, but on the other hand, it was revealed that some microorganisms can survive and grow in sulfite-added fermenting must. We also analyzed 15 samples of commercial wines by the PCR-DGGE method and detected various microorganisms. Among them, Sphingomonas sp., Pseudozyma sp., Ochromonas sp. and Methylophilus sp. were found for the first time in wine as far as we know. We did not identify a specific microorganism that was detected only from wines without sulfite addition. Thus, the microbiota of end-products seemed to be influenced by other factors, such as filtration before bottling, the production equipment and the storage environment. PMID- 24239026 TI - Nuclear magnetic resonance relaxation characterisation of water status of developing grains of maize (Zea mays L.) grown at different nitrogen levels. AB - Changes in water status of developing grains of maize (Zea mays L.) grown under different nitrogen levels were characterized by nuclear magnetic resonance (NMR) spectroscopy. There were distinct changes in water status of grains due to the application of different levels of nitrogen (0, 120 and 180 kg N ha(-1)). A comparison of the grain developmental characteristics, composition and physical properties indicated that, not only the developmental characteristics like grain weight, grain number/ear, and rate of grain filling increased, but also bound water characterized by the T2 component of NMR relaxation increased with nitrogen application (50-70%) and developmental stages leading to maturation (10-60%). The consistency in the patterns of responses to free water and intermediate water to increasing levels of nitrogen application and grain maturity suggested that nitrogen application resulted in more proportion of water to both bound- and intermediate states and less in free state. These changes are further corroborated by the concomitant increases in protein and starch contents in grains from higher nitrogen treatments as macromolecules like protein and starch retain more amount of water in the bound state. The results of the changes in T2 showed that water status during grain development was not only affected by developmental processes but also by nitrogen supply to plants. This study strongly indicated a clear nutrient and developmental stage dependence of grain tissue water status in maize. PMID- 24239029 TI - Isolated calcaneocuboid joint tuberculosis: a rare case report. AB - Tubercular arthritis affecting the foot is uncommon. Isolated calcaneocuboid joint tuberculosis has never been reported in the literature. Herein we report a case of 43-year-old male who presented with insidious onset pain in hindfoot of 4 months duration. Radiograph revealed destruction of calcaneocuboid joint along with cuboid. Computed Tomography scan further consolidated the findings. Diagnosis was confirmed from aspiration from joint with culture of mycobacterium tuberculosis. Anti-tubercular chemotherapy was started and good clinical response was noted. We reported this case because of its rarity to involve calcaneocuboid joint and the excellent outcome with medical treatment. PMID- 24239027 TI - Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade. AB - OBJECTIVE: To evaluate the trends in urine aquaporin-1 (AQP1) and perilipin 2 (PLIN2) concentrations in patients with clear cell and papillary renal cell carcinoma (RCC), we determined the relationship between the urine concentration of these biomarkers and tumor size, grade, and stage. MATERIALS AND METHODS: The biomarker concentrations were determined by sensitive and specific Western blot procedures normalized to the urine creatinine excretion. The analysis included 61 patients undergoing partial or radical nephrectomy for clear cell or papillary RCC and 43 age- and sex-matched control patients. Relationships between urine biomarker concentrations and tumor size, stage, and grade were assessed. RESULTS: Patients with RCC had 35-fold and 9-fold higher median urinary AQP1 and PLIN2 concentrations, respectively, compared with controls. Both tumor markers decreased after tumor resection to concentrations equivalent to those of controls. The sensitivity and specificity were both 100% for AQP1 and 92% and 100%, respectively, for PLIN2. A significant linear correlation was found between the tumor size and the prenephrectomy AQP1 (Spearman coefficient 0.78, P <.001) and PLIN2 (Spearman coefficient 0.69, P <.001) concentrations. A correlation was found for both markers with tumor stage (overall P = .030), when the stage was dependent primarily on the tumor size (stages T1 and T2), but not with stage T3, which reflected extrarenal spread. Neither marker showed a significant correlation with tumor grade. CONCLUSION: AQP1 and PLIN2 were significantly increased in patients with clear cell and papillary RCC compared with controls. The preoperative urinary concentrations of these markers reflected the tumor size and stage. PMID- 24239028 TI - AKAP signaling complexes: pointing towards the next generation of therapeutic targets? AB - A-kinase anchoring proteins (AKAPs) streamline signal transduction by localizing signaling enzymes with their substrates. Great strides have been made in elucidating the role of these macromolecular signaling complexes as new binding partners and novel AKAPs are continually being uncovered. The mechanics and dynamics of these multi-enzyme assemblies suggest that AKAP complexes are viable targets for therapeutic intervention. This review will highlight recent advances in AKAP research focusing on local signaling events that are perturbed in disease. PMID- 24239030 TI - Interim versus standard methadone treatment: a benefit-cost analysis. AB - A benefit-cost analysis was conducted as part of a clinical trial in which newly admitted methadone patients were randomly assigned to interim methadone (IM; methadone without counseling) for the first 4 months of 12 months of methadone treatment or 12 months of methadone with one of two counseling conditions. Health, residential drug treatment, criminal justice costs, and income data in 2010 dollars were obtained at treatment entry, and 4- and 12-month follow-up from 200 participants and program costs were obtained. The net benefits of treatment were greater for the IM condition but controlling for the baseline variables noted above, the difference between conditions in net monetary benefits was not significant. For the combined sample, there was a pre- to post-treatment net benefit of $1470 (95% CI: -$625; $3584) and a benefit-cost ratio of 1.5 (95% CI: 0.8, 2.3), but using our conservative approach to calculating benefits, these values were not significant. PMID- 24239032 TI - Chronic nonspecific low back pain: rehabilitation. PMID- 24239031 TI - [Knowledge about radon and its associated risk perception in France]. AB - PURPOSE: Radon exposure is a major environmental risk in health. It remains badly known by the general population. It is the second cause of lung cancer, after tobacco smoking. The aim of this cross-sectional general population survey was to describe radon exposure risk knowledge and the socioeconomic factors related to this knowledge. MATERIALS AND METHODS: The Cancer Barometer survey 2010 questioned the French population about its knowledge of radon as such and as health risk factor. This survey was a two-stage random sampling with computer assisted telephone interview that was performed from April 3, 2010 to August 7, 2010 on a sample of 3,359 people aged 15 to 75 years old. RESULTS: Among people aged 15 to 75 years old, only one in five knows that radon is a natural gas coming from the ground. This knowledge is more frequent among people living in an area that is directly concerned by radon, among men and increases with age, with the level of education and the level of income. Radon risk remains still widely underestimated by the general public, including in areas concerned by this risk. When people were confronted with radon exposure, few intended to remedy by improving their home. CONCLUSION: The success of prevention initiatives implies the support and the collaboration of various national and local actors. To improve their impact for the prevention of lung cancers, it could be more effective to couple these actions with prevention messages on tobacco. PMID- 24239034 TI - Does the presence of the fibronectin-aggrecan complex predict outcomes from lumbar discectomy for disc herniation? AB - BACKGROUND CONTEXT: Protein biomarkers associated with lumbar disc disease have been studied as diagnostic indicators and therapeutic targets. Recently, a cartilage degradation product, the fibronectin-aggrecan complex (FAC) identified in the epidural space, has been shown to predict response to lumbar epidural steroid injection in patients with radiculopathy from herniated nucleus pulposus (HNP). PURPOSE: Determine the ability of FAC to predict response to microdiscectomy for patients with radiculopathy due to lumbar disc herniation STUDY DESIGN/SETTING: Single-center prospective consecutive cohort study. PATIENT SAMPLE: Patients with radiculopathy from HNP with concordant symptoms to MRI who underwent microdiscectomy. OUTCOMES MEASURES: Oswestry disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3-month follow-up. Primary outcome of clinical improvement was defined as patients with both a decrease in VAS of at least 3 points and ODI >20 points. METHODS: Intraoperative sampling was done via lavage of the excised fragment by ELISA for presence of FAC. Funding for the ELISA was provided by Cytonics, Inc. RESULTS: Seventy-five patients had full complement of data and were included in this analysis. At 3 month follow-up, 57 (76%) patents were "better." There was a statistically significant association of the presence of FAC and clinical improvement (p=.017) with an 85% positive predictive value. Receiver-operating-characteristic (ROC) curve plotting association of FAC and clinical improvement demonstrates an area under the curve (AUC) of 0.66+/-0.08 (p=.037). Subset analysis of those with weakness on physical examination (n=48) plotting the association of FAC and improvement shows AUC on ROC of 0.81+/-0.067 (p=.002). CONCLUSIONS: Patients who are "FAC+" are more likely to demonstrate clinical improvement following microdiscectomy. The data suggest that the inflammatory milieu plays a significant role regarding improvement in patients undergoing discectomy for radiculopathy in lumbar HNP, even in those with preoperative weakness. The FAC represents a potential target for treatment in HNP. PMID- 24239033 TI - Effect of placenta previa on neonatal respiratory disorders and amniotic lamellar body counts at 36-38weeks of gestation. AB - BACKGROUND: Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. AIMS: The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic lamellar body count (LBC) values. METHODS: We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36-38weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. RESULTS: RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P=0.002 and P=0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58-7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P=0.046). CONCLUSIONS: Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36 38weeks of gestation. PMID- 24239035 TI - [Gynaecology and obstetrics in Basse-Normandy: demographic perspectives in 15 years]. AB - OBJECTIVES: The French population is growing and ageing. In this context, it is important to consider the future of gynecologists and obstetricians in Basse Normandie. The aim of this study was to perform an overview of the demographics of practitioners and estimate the retirements. We also try to project the need of trainees for the next years. MATERIALS AND METHODS: We conducted a demographic and workload survey among 142 practitioners and 35 trainees. We detailed retirements and arrivals of this population. RESULTS: By 2025, nearly two-thirds of practitioners in 2012 will retire, including 100% of medical gynecologists. Otherwise, there will be a lack of 1 to 2 practitioners per year. We also noted the tendance of feminization (86%) and the wish of a multi-practice in public hospital (86%). CONCLUSION: A reflection about the health planning will be necessary in order to answer the demographics difficulty in the region. We will have to take into account the future retirements and also the specific situations in each area. PMID- 24239036 TI - [Factors predicting unsuccessful labor induction with dinoprostone in post-term pregnancy with unfavorable cervix]. AB - OBJECTIVE: To identify predictive factors for unsuccessful induction of labor within 24hours after dinoprostone insertion in post-term pregnancy with unfavorable cervix. MATERIAL AND METHODS: We retrospectively reviewed 325 singleton pregnancies with a diagnosis of post-term pregnancy and unfavorable cervix (Bishop score<6) during the period January 2012-Decembre 2012. Patients were classified into 2 groups: successful labor, defined as cervical ripening, within 24hours after dinoprostone insertion (Group R; n=248; 76.3 %) or failure group (Group E; n=77; 23.7 %). Antepartum and perpartum characteristics of women were compared. RESULTS: Nulliparity (74.0 versus 56.0 %; OR=2.23; 95 % CI: 1.27 4.00; P=0.005), gestational age <=41 SA+4 (53.2 versus 33.9 %; OR=2.22; 95 % CI: 1.32-3.74; P=0.003) and history of dilatation and curettage (27.3 versus 10.5 %; OR=3.19; 95 % CI: 1.66-6.11; P=0.0005) were significantly associated with unsuccessful induction of labor. Bishop score was significantly higher in Group R (3.6 versus 1.9; P=0.001). Also, consistency (74.0 versus 44.4 %; OR=3.57; 95 % CI: 2.04-6.40; P<10(-5)) and absence of dilatation of the cervix (59.7 versus 23.0 %; OR=4.97; 95 % CI: 2.89-8.56; P<10(-6)) were identified as significant predictive factors for unsuccessful induction of labor. CONCLUSION: Nulliparity, gestational age <=41 SA+4, history of dilatation and curettage and Bishop score, in particular consistency and dilatation, are correlated with failure of cervical ripening in post-term pregnancy with unfavorable cervix. PMID- 24239037 TI - Simultaneous determination of trihalomethanes and organochlorine pesticides in water samples by direct immersion-headspace-solid phase microextraction. AB - In this study the extraction conditions for the simultaneous extraction of volatile (trihalomethanes - THM) and semi-volatile (organochlorine pesticides) compounds from water samples by direct immersion-headspace-solid phase microextraction (DI-HS-SPME) were optimized and compared. The extraction efficiencies of the proposed DI-HS-SPME and traditional SPME modes were also compared. The separation and detection were performed by gas chromatography-mass spectrometry in SIM mode (GC-MS-SIM). The variables evaluated were extraction time, extraction temperature and added volume of aqueous NaCl solution at 20% (m/v). Central composite designs were carried out to determine the optimal extraction conditions for each SPME mode. The optimal condition for the DI-HS SPME mode was 80min of total extraction time (64min at 70 degrees C in DI-SPME mode and 16min at 12 degrees C in HS-SPME mode) with 5mL of 20% (m/v) NaCl solution. The SPME extraction modes were compared and the DI-HS-SPME produced excellent results for both volatile and semi-volatile compounds. This represents a promising alternative for the analysis of matrices that contain compounds with very different ranges of volatility. The analytical figures of merit were evaluated and good results were obtained using this procedure for both classes of compounds studied. The limit of quantitation ranged from 0.02 to 2.0MUgL(-1) for organochlorine pesticides and from 0.30 to 0.77MUgL(-1) for THM. PMID- 24239038 TI - Highly crosslinked polymeric monoliths with various C6 functional groups for reversed-phase capillary liquid chromatography of small molecules. AB - Three crosslinking monomers, i.e., 1,6-hexanediol dimethacrylate (HDDMA), cyclohexanediol dimethacrylate (CHDDMA) and 1,4-phenylene diacrylate (PHDA), were used to synthesize highly cross-linked monolithic capillary columns for reversed phase liquid chromatography (RPLC) of small molecules. Selection of porogen type and concentration was investigated in detail. Isocratic elution of alkylbenzenes at a flow rate of 300nL/min was performed using HDDMA and CHDDMA monolithic columns. Gradient elution of alkylbenzenes using all three monolithic columns showed good separations. Optimized monoliths synthesized from all three crosslinking monomers possessed high permeabilities. Poly(HDDMA) monoliths demonstrated column efficiencies up to 86,000 plates/m. Column preparation of poly(HDDMA) monolithic columns was highly reproducible; the relative standard deviation (RSD) values (n=3) for run-to-run and column-to-column were less than 0.26% and 0.70%, respectively, based on retention times of alkylbenzenes. PMID- 24239039 TI - Simultaneous determination of allantoin and glycolic acid in snail mucus and cosmetic creams with high performance liquid chromatography and ultraviolet detection. AB - A new methodology for simultaneous quantitative analysis of allantoin and glycolic acid in snail mucus and cosmetic creams was developed. HPLC separation was achieved a Synergi-Hydro RP column within 7min using isocratic elution with potassium phosphate (pH 2.7; 10mM) at a flow rate of 0.7mL/min at 30 degrees C. Sample pretreatment was performed by dilution of mucus or cosmetic cream in the elution buffer, heating at 60 degrees C for 20min, adjusting the pH to 2.9 and purification with hexane extraction. Linearity was determined with spiked samples and the LLOQ values of 0.0125 and 0.2500mg/mL were determined for allantoin and glycolic acid, respectively. Accuracy and intra- and inter-day repeatability were studied at three levels of concentrations (0.04, 0.08 and 0.16mg/mL for allantoin and 0.1, 1.5 and 4.0mg/mL for glycolic acid) using spiked mucus and cream base samples; mean values of recovery were in the range of 96.81-102.42% in all matrices tested, whereas the respective RSDs (%Relative Standard Deviation) were less than 3.04% in all cases. Spiked mucus and cream samples were stable (RSD<4.16 and relative error<4.34%) at room temperature and at 4 degrees C for 1 week and at -18 degrees C for 6 months; samples were also stable after three freeze-thaw cycles. The method was applied to the analysis of different lots of snail mucus, and of three commercial creams containing snail mucus. PMID- 24239040 TI - Oriented immobilization of peptide-N-glycosidase F on a monolithic support for glycosylation analysis. AB - In this paper, we report on a novel oriented peptide-N-glycosidase F (PNGase F) immobilization approach onto methacrylate based monolithic support for rapid, reproducible and efficient release of the N-linked carbohydrate moieties from glycoproteins. The glutathione-S-transferase-fusion PNGase F (PNGase F-GST) was expressed in Escherichia coli using regular vector technology. The monolithic pore surface was functionalized with glutathione via a succinimidyl-6-(iodoacetyl amino)-hexanoate linker and the specific affinity of GST toward glutathione was utilized for the oriented coupling. This novel immobilization procedure was compared with reductive amination technique commonly used for non-oriented enzyme immobilization via primary amine functionalities. Both coupling approaches were compared using enzymatic treatment of several glycoproteins, such as ribonuclease B, fetuin and immunoglobulin G followed by MALDI/MS and CE-LIF analysis of the released glycans. Orientedly immobilized PNGase F via GST-glutathione coupling showed significantly higher activity, remained stable for several months, and allowed rapid release of various types of glycans (high-mannose, core fucosylated, sialylated, etc.) from glycoproteins. Complete protein deglycosylation was obtained as fast as in several seconds when using flow through immobilized microreactors. PMID- 24239041 TI - Neurocutaneous melanosis in children with giant congenital melanocytic nevi. AB - Twenty-four children with giant congenital melanocytic nevi underwent brain MRI at 1.5 T scanner. Melanin deposits in the brain were found in seven children (29.2%) located in temporal lobes, thalamus, cerebellum, and pons. One patient showed leptomeningeal involvement. Six patients were asymptomatic, and one had epilepsy. As opposed to previous reports, localization of skin nevi on anterior part of trunk was correlated to central nervous system involvement. In all patients with brain involvement skin nevi showed picture of compound nevus with neurofibromatic component. PMID- 24239042 TI - I-SCAN targeted versus random biopsies in Barrett's oesophagus. AB - BACKGROUND: The accuracy and effectiveness of targeted oesophageal biopsies in Barrett's oesophagus to detect dysplasia using new magnification techniques are unknown. Aim of this study was to investigate whether the combined use of acetic acid, magnification and electronic filters allows the same accuracy as the four quadrant random biopsies pattern; pathologist interobserver agreement both in low grade and high grade dysplasia was also assessed. METHODS: Fifty-four consecutive patients newly diagnosed with Barrett's oesophagus were enrolled in a prospective study from a single endoscopy unit. Biopsies were evaluated by the local pathologist and by an expert pathologist from another pathology unit. MAIN OUTCOME MEASUREMENT: Dysplasia detection rate and interobserver agreement for the histologic diagnosis of dysplasia. RESULTS: The use of acetic acid, magnification and electronic filters showed an unacceptably low dysplasia detection rate by the two pathologists (9.2% and 5.5% for targeted biopsies, respectively). The interobserver agreement for low grade dysplasia between pathologists was low (Cohen's K weighted=0.45). CONCLUSIONS: In an average setting, the standard four quadrant method should still be preferred, along with the implementation of a routine second evaluation by an expert pathologist. PMID- 24239043 TI - IL-2 is a gradually proved potential therapeutic target for hepatocellular carcinoma. PMID- 24239045 TI - Dysbiosis--a consequence of Paneth cell dysfunction. AB - The complex community of colonizing microbes inhabiting the mucosal surfaces of mammals is vital to homeostasis and normal physiology in the host. When the composition of this microbiota is unfavorably altered, termed dysbiosis, the host is rendered more susceptible to a variety of chronic diseases. In the mammalian small intestine, specialized secretory epithelial cells, named Paneth cells, produce a variety of secreted antimicrobial peptides that fundamentally influence the composition of the microbiota. Recent investigations have identified numerous genetic and environmental factors that can disrupt normal Paneth cell function, resulting in compromised antimicrobial peptide secretion and consequent dysbiosis. These findings suggest that Paneth cell dysfunction should be considered a common cause of dysbiosis. PMID- 24239044 TI - A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: the TT4 randomized trial. AB - BACKGROUND: Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4). METHOD: 267 naive HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n=180) or current standard-of care (SoC, n=87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease <=2log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment. RESULTS: Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1 SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25+/-15 vs. 36+/-12.1 weeks], and for subgroups: G1 [35.3+/-16.7 vs. 47.3+/-2.6 weeks], G2 [18.3+/-7.5 vs. 24+/-2.8 weeks], G3 [15.2+/-8.7 vs. 22.8+/ 3 weeks] and G4 [26.9+/-13 vs. 48 weeks]. CONCLUSIONS: In HCV-naive patients, TT4 rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction. PMID- 24239046 TI - Negative regulatory receptors of the IL-1 family. AB - The IL-1 family of ligands and receptors has a central role in both innate and adaptive immune responses and is tightly controlled by antagonists, decoy receptors, scavengers, dominant negative molecules, miRNAs and other mechanisms, acting extracellularly or intracellularly. During evolution, the development of multiple mechanisms of negative regulation reveals the need for tight control of the biological consequences of IL-1 family ligands in order to balance local and systemic inflammation and limit immunopathology. Indeed, studies with gene targeted mice for negative regulators and genetic studies in humans provide evidence for their non-redundant role in controlling inflammation, tissue damage and adaptive responses. In addition, studies have revealed the need of negative regulation of the IL-1 family not only in disease, but also in homeostatic conditions. In this review, the negative regulation mediated by decoy receptors are presented and include IL-1R2 and IL-IL-18BP as well as atypical receptors, which include TIR8/SIGIRR, IL-1RAcPb, TIGIRR-1 and IL-1RAPL. Particular emphasis is given to IL-1R2, since its discovery is the basis for the formulation of the decoy paradigm, now considered a general strategy to counter the primary inflammatory activities of cytokines and chemokines. Emphasis is also given to TIR8, a prototypical negative regulatory receptor having non-redundant roles in limiting inflammation and adaptive responses. PMID- 24239047 TI - Prevalence of autotransporters in Escherichia coli: what is the impact of phylogeny and pathotype? AB - Autotransporter (AT) proteins are widespread surface-exposed or secreted factors in Escherichia coli. Several ATs have been correlated with pathogenesis or specific phylogenetic lineages. Therefore, an application as biomarkers for individual extraintestinal pathogenic E.coli (ExPEC) or intestinal pathogenic E.coli (IPEC) has been proposed. To put this assumption on a solid foundation, we analyzed 111 publicly available E. coli genome sequences and screened them bioinformatically for the presence of 18 ATs. We determined the highest AT prevalence per strain in phylogroup B2 isolates and showed that AT distribution correlates rather with phylogenetic lineages than with pathotypes. Although a strict dependence between AT prevalence and pathotype was not observed, EspP, EhaA, and EhaG cluster with IPEC of phylogroup B1 and E, respectively, whereas UpaH is predominantly present in ExPEC of phylogroup B2. Furthermore, PicU, SepA, UpaB, UpaI, and UpaJ were associated with phylogroup B2. We detected UpaI and its positional ortholog EhaC in 93% of the E.coli strains tested. This AT variant is thus the most prevalent in E.coli irrespective of pathotype or phylogenetic background. Compared with the ATs UpaB, UpaC, and UpaJ of uropathogenic E.coli strain 536, UpaI had redundant functions, contributing to autoaggregation, biofilm formation, and binding to extracellular matrix proteins. The functional redundancy and wide distribution of ATs among pathogenic and non-pathogenic E.coli indicates that ATs cannot generally be regarded as specific biomarkers and virulence factors. Our results demonstrate that phylogeny has a bigger impact on the distribution of AT variants in E.coli than initially thought, especially in ExPEC. PMID- 24239048 TI - Neural circuitry of masked emotional face processing in youth with bipolar disorder, severe mood dysregulation, and healthy volunteers. AB - Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N=20), SMD (N=18), and HV (N=22) during "Aware" and "Non-aware" priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval) appeared (187 ms) before the shape. In non-aware, a face appeared (17 ms), followed by a mask (170 ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders. PMID- 24239050 TI - Dysnatremias in patients with kidney disease. AB - Dysnatremias are among the most common electrolyte disorders in clinical medicine. Recent studies have shown that individuals with chronic kidney disease also are afflicted by these electrolyte disorders. Furthermore, their presence imparts an increased risk of mortality. In this review, we discuss studies in experimental animals and in humans that have attempted to establish the mechanisms responsible for limiting urinary dilution and urinary concentration in progressive kidney disease. The clinical implications of these disorders in water excretion are discussed in the setting of optimal water intake as kidney disease progresses. This review emphasizes the management of patients with chronic kidney disease who have marked abnormalities in serum sodium concentrations and gives specific recommendations for modifications in renal replacement therapy prescription in hyponatremic patients with end-stage renal disease. PMID- 24239049 TI - Gaining insight into adolescent vulnerability for social anxiety from developmental cognitive neuroscience. AB - Social anxiety disorder (SAD) markedly impairs daily functioning. For adolescents, SAD can constrain typical development precisely when social experiences broaden, peers' opinions are highly salient, and social approval is actively sought. Individuals with extreme, impairing social anxiety fear evaluation from others, avoid social interactions, and interpret ambiguous social cues as threatening. Yet some degree of social anxiety can be normative and non impairing. Furthermore, a temperament of behavioral inhibition increases risk for SAD for some, but not all adolescents with this temperament. One fruitful approach taken to understand the mechanisms of social anxiety has been to use neuroimaging to link affect and cognition with neural networks implicated in the neurodevelopmental social reorientation of adolescence. Although initial neuroimaging studies of adolescent SAD and risk for SAD underscored the role of fear-processing circuits (e.g., the amygdala and ventral prefrontal cortex), recent work has expanded these circuits to include reward-processing structures in the basal ganglia. A growing focus on reward-related neural circuitry holds promise for innovative translational research needed to differentiate impairing from normative social anxiety and for novel ways to treat adolescent SAD that focus on both social avoidance and social approach. PMID- 24239051 TI - Diagnostic tests and treatment options in glomerular disease: 2014 update. AB - Glomerular diseases historically have been challenging disorders to comprehend and treat for patients and physicians alike. Kidney biopsy is the gold standard of diagnosis, but the link between pathophysiology and the histologic representation of kidney injury has remained elusive in many of these diseases. As a result, treatment of glomerular disease usually involves therapies that are not specific to disease pathogenesis, such as blockade of the renin-angiotensin aldosterone system and various immunosuppression regimens. Recent research has resulted in greater insight into some glomerular diseases, leading to the hope that new diagnostic tests and treatments targeting disease-specific mechanisms are on the horizon. We review recent progress on the understanding, diagnosis, and treatment of 4 glomerular diseases: immunoglobulin A nephropathy, focal segmental glomerulosclerosis, the C3 glomerulopathies, and idiopathic membranous nephropathy. PMID- 24239052 TI - Therapeutic education in coronary heart disease: position paper from the Working Group of Exercise Rehabilitation and Sport (GERS) and the Therapeutic Education Commission of the French Society of Cardiology. AB - Cardiovascular mortality has decreased over the past 25 years, largely because of acute coronary syndrome care and preventive actions. Nevertheless, the rate of coronary heart disease remains high, with an annual risk of 4.7% (cardiac mortality, myocardial infarction, stroke). Cardiovascular risk factor management must be a priority in primary and secondary prevention, to improve the prognosis of this severe disease, in which absence of symptoms does not mean benignity. The current goals of therapeutic patient education are smoking cessation, regular physical activity, a cardioprotective (Mediterranean) diet, management of stress, good treatment adherence (which improves compliance), judicious use of the care system and help with occupational reintegration. Current and future programmes must be in accordance with the Haute Autorite de Sante recommendations published in 2007. PMID- 24239053 TI - Promises and limitations of hitchhiking mapping. AB - Building the connection between genetic and phenotypic variation is an important 'work in progress', and one that will enable proactive diagnosis and treatment in medicine, promote development of environment-targeted varieties in agriculture, and clarify the limits of species adaptation to changing environments in conservation. Quantitative trait loci (QTL) mapping and genome wide association (GWA) studies have recently been allied to an additional focus on 'hitchhiking' (HH) mapping--using changes in allele frequency due to artificial or natural selection. This older technique has been popularized by the falling costs of high throughput sequencing. Initial HH-resequensing experiments seem to have found many thousands of polymorphisms responding to selection. We argue that this interpretation appears too optimistic, and that the data might in fact be more consistent with dozens, rather than thousands, of loci under selection. We propose several developments required for sensible data analyses that will fully realize the great power of the HH technique, and outline ways of moving forward. PMID- 24239054 TI - Response to "Jones L., Jones J., Martin C., Platt S., Response to Cross-sectional study of ethnic differences in the utility of area deprivation measures to target socioeconomically deprived individuals". PMID- 24239055 TI - Invited commentary on Death of a child and parental wellbeing in old age: evidence from Taiwan. PMID- 24239056 TI - Factors associated with perceived stigma of epilepsy in Croatia: a study using the revised Epilepsy Stigma Scale. AB - PURPOSE: It is believed that a large number of factors influence feelings of stigma, but their relative contribution is not yet entirely clear. Most studies to date were conducted using the Epilepsy Stigma Scale (ESS); only one used a revised version of the ESS (rESS). The following study aims to determine factors contributing to epilepsy stigma in outpatients with chronic epilepsy in Croatia, and to analyze some psychometric properties of the Croatian translation of the rESS. METHODS: Alongside standard testing for validity of the scale, a simulation model of the original ESS (smESS) was created. This model, which does not include a grading Likert 0-3 scale, was compared with the rESS. RESULTS: In total, 159 out of 298 subjects (53%) reported feeling stigmatised, with 136 (45%) mild to moderately and 23 (8%) highly. Internal consistency of the Croatian translation of the rESS was 0.887. Feelings of stigma were significantly associated with age <= 50 years, younger age of epilepsy onset, more than 50 seizures to date, generalized tonic-clonic seizures, and a shorter seizure-free period. Multiple stepwise regression showed number of seizures to date as a significant variable (Beta=0.246). By adapting data into the smESS significant associations with younger age and age of epilepsy onset were lost. Internal consistency of the smESS was 0.849. CONCLUSIONS: The Croatian translation of the rESS has been proved to be a suitable instrument for diagnosing epilepsy stigma. The results of our model point to the possibility that the rESS might be more sensitive than the original ESS. PMID- 24239057 TI - Clinical, electrophysiological and magnetic resonance findings in a family with hereditary neuropathy with liability to pressure palsies caused by a novel PMP22 mutation. AB - Hereditary neuropathy with liability to pressure palsies (HNPP) is a disorder mainly caused by a 1.5-Mb deletion at 17p11.2-12 (and in some rare cases by point mutations) and clinically associated with recurrent painless palsies. Here, we performed electrophysiological (motor, sensory and terminal latency index), MRI and genetic studies in a family referred for ulnar neuropathy with pain. Surprisingly, we found typical neurophysiological features of HNPP (prolongation of distal motor latencies and diffuse SNCV slowing with significant slowing of motor nerve conduction velocities). Besides, the proband presented conduction block in left ulnar, left median and both peroneal nerves. MRI findings were consistent with an underlying neuropathy. Molecular studies identified a novel frameshift mutation in PMP22 confirming the diagnosis of HNPP. Our data suggest that neurophysiological studies are essential to characterize underdiagnosed HNPP patients referred for peripheral neuropathy. Our experience shows that MRI could be a complementary tool for the diagnosis of these patients. PMID- 24239058 TI - Outcome of children with acetylcholine receptor (AChR) antibody positive juvenile myasthenia gravis following thymectomy. AB - Most evidence supporting the benefit of thymectomy in juvenile myasthenia gravis (JMG) is extrapolated from adult studies, with only little data concerning paediatric populations. Here we evaluate the outcome of children with generalized JMG who underwent thymectomy between 1996 and 2010 at 2 tertiary paediatric neurology referral centres in the United Kingdom. Twenty patients (15 female, 5 male), aged 13months to 15.5years (median 10.4years) at disease onset, were identified. Prior to thymectomy, disease severity was graded as IIb in 3, III in 11, and IV in 6 patients according to the Osserman classification. All demonstrated positive anti-acetylcholine receptor (AChR) antibody titres. All patients received pyridostigmine and 14 received additional steroid therapy. Transternal thymectomy was performed at the age of 2.7-16.6years (median 11.1years). At the last follow-up (10months to 10.9years, median 2.7years, after thymectomy), the majority of children demonstrated substantial improvement, although some had required additional immune-modulatory therapies. About one third achieved complete remission. The postoperative morbidity was low. No benefit was observed in one patient with thymoma. We conclude that thymectomy should be considered as a treatment option early in the course of generalised AChR antibody-positive JMG. PMID- 24239059 TI - Anoctamin 5 muscular dystrophy associated with a silent p.Leu115Leu mutation resulting in exon skipping. AB - We report a 45year-old patient with an asymmetrical proximal muscle weakness affecting the quadriceps muscle of the right leg starting at the age of 32years. CK was 25-fold increased. MRI of the legs showed signs of fatty degeneration more pronounced in the right side. Biopsy of a thigh muscle showed dystrophic pattern and amyloid deposition in blood vessel walls. The coding region and exon/intron boundaries of the ANO5 gene were amplified and sequenced. The common c.191dupA mutation and a silent novel p.Leu115Leu (c.345G>A) variant were identified. This silent variant was listed neither in the LOVD database nor in the SNP database. To evaluate the pathogenicity of the novel silent mutation in ANO5, cDNA analysis was performed that demonstrated skipping of exon 6. So far, no case with a silent mutation leading to abnormal splicing has been identified in Anoctamin 5 muscular dystrophy. Present findings emphasize that cDNA analysis should be done if a silent variant is not annotated in the databases. In Anoctamin 5 muscular dystrophy a molecular diagnosis is even more important as protein investigation through Western blotting or immunohistochemistry is not yet established. PMID- 24239060 TI - Novel TPM3 mutation in a family with cap myopathy and review of the literature. AB - Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three generations, caused by a novel heterozygous mutation in the alpha-tropomyosin slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6-10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n=11), thus far reported in the literature. PMID- 24239061 TI - A case of mobile aortic arch thrombus with systemic embolisation--a management dilemma. AB - We report the case of splenic infarct secondary to embolisation from a polypoid 17 mm*10 mm thoracic aorta thrombi in a 60 year-old female. The management and prognostic value of thoracic aorta thrombi are poorly defined in literature. This patient was successfully treated with oral anticoagulation as opposed to surgical intervention. Repeat transoesophageal echocardiography and computed tomography have demonstrated marked reduction in thrombi size with no further embolic event. PMID- 24239062 TI - Attributed meanings and strategies to prevent challenging behaviors of hospitalized children with autism: two perspectives. AB - INTRODUCTION: Understanding is limited of the meaning attributed to behaviors of children with autism spectrum disorder and strategies used to prevent challenging behaviors in the context of hospitalization. METHODS: This qualitative study consisted of two focus groups (n = 10; five mothers and five health care providers [HCPs]). Transcripts were analyzed using the qualitative method of narrative inquiry. RESULTS: The meaning attributed to behaviors by the mothers and the HCPs differed. The mothers attributed behaviors to the child's communication of frustration, hyperactivity, and self-calming. The HCPs attributed challenging behaviors to self-stimulation and child aggression. Strategies to prevent behaviors also differed. Mothers focused on preparation prior to hospitalization and attempts to partner with HCPs. HCPs identified fewer strategies and consulted mothers for strategies to manage challenging behaviors. DISCUSSION: HCP and parent collaboration could lead to strategies to increase supports for children with autism spectrum disorder in the hospital to decrease their frustration and challenging behaviors. PMID- 24239063 TI - The neuroimmune basis of fatigue. AB - The exact nature and pathophysiology of fatigue remain largely elusive despite its high prevalence in physically ill patients. Studies on the relationship between the immune system and the central nervous system provide a new perspective on the mechanisms of fatigue. Inflammatory mediators that are released by activated innate immune cells at the periphery and in the central nervous system alter the metabolism and activity of neurotransmitters, generate neurotoxic compounds, decrease neurotrophic factors, and profoundly disturb the neuronal environment. The resulting alterations in fronto-striatal networks together with the activation of insula by inflammatory interoceptive stimuli underlie the many dimensions of fatigue including reduced incentive motivation, decreased behavioral flexibility, uncertainty about usefulness of actions, and awareness of fatigue. PMID- 24239064 TI - Risk factors for levofloxacin resistance in Stenotrophomonas maltophilia from respiratory tract in a regional hospital. AB - OBJECTIVES: Stenotrophomonas maltophilia is a bacterial pathogen associated with health-care associated infections, particularly in immunocompromised patients. Members of the fluoroquinolone drug class are frequently used to treat S. maltophilia infection; however, S. maltophilia resistance to fluoroquinolones, especially levofloxacin, has been increasing. METHODS: We sought to identify risk factors associated with levofloxacin resistance using a case-control study. We examined sputum from 76 S. maltophilia-positive patients admitted to our hospital between January 1, 2010 and June 30, 2011. Case groups were defined as patients who had S. maltophilia infections resistant to levofloxacin, and control groups were defined as patients who had S. maltophilia infections susceptible to levofloxacin treatment. Patient information including demographics, previous antibiotic use, and other traits were recorded. In addition, S. maltophilia isolates from patient sputum were assessed for antibiotic resistance as well as for the presence of genes associated with drug resistance. RESULTS: Previous antibiotic treatment with first- or second-generation cephalosporin was found more often in the levofloxacin-susceptible group; by contrast, previous piperacillin/tazobactam treatment occurred more often in the levofloxacin resistant group. Three genes associated with drug resistance, including SmeA, SmeD, and SpgM were not significantly different between these groups. CONCLUSION: Piperacillin/tazobactam treatment is associated with subsequent isolation of levofloxacin-resistant S. maltophilia from the respiratory tract. PMID- 24239065 TI - Risk factors of community-onset urinary tract infections caused by plasmid mediated AmpC beta-lactamase-producing Enterobacteriaceae. AB - BACKGROUND: The AmpC beta-lactamase (AmpC)-producing Enterobacteriaceae emerged worldwide. This study was conducted to determine the risk factors of community onset urinary tract infections (UTIs) caused by plasmid-mediated AmpC-producing Enterobacteriaceae. METHODS: Patients who were diagnosed as community-onset UTIs caused by Enterobacteriaceae in a tertiary-care teaching hospital from December 2010 to January 2012 were included. Extended-spectrum beta-lactamase (ESBL) producing isolates were excluded. We identified plasmid-mediated AmpC-producing Enterobacteriaceae both phenotypically (by disk potentiation test and double-disk synergy test) and genotypically (by Multiplex polymerase chain reaction (PCR) assay). The demographic data, clinical characteristics, and risk factors of acquisition were described. RESULTS: Among the 323 non-ESBL-producing Enterobacteriaceae identified in community-onset UTIs, 50 isolates were phenotypically positive for AmpC. Escherichia coli was the most common AmpC producing organism (60%), followed by Klebsiella pneumonia (8%), and Enterobacter cloacae and Proteus mirabilis (6% for each species). The independent risk factors for acquisition of AmpC-producing Enterobacteriaceae included prior history of cerebral vascular accident [odds ratio (OR) = 2.014; 95% confidence interval (CI) = 1.007-4.031; p = 0.0048], and prior use of fluoroquinolones (OR = 4.049; 95% CI = 1.759-9.319; p = 0.001) and cephamycin (OR = 9.683; 95% CI = 2.007-45.135; p = 0.004). AmpC-producing isolates were multidrug resistant. Carbapenems, cefepime, and piperacillin/tazobactam had the best in vitro efficacy. The most commonly identified plasmid-mediated AmpC gene was bla(CIT), followed by bla(DHA)/bla(EBC), and bla(MOx). CONCLUSION: For community-onset UTIs, AmpC producing Enterobacteriaceae should be suspected in those with prior history of cerebral vascular accident and prior use of antimicrobials. To treat these multiple-resistant isolates, carbapenems, cefepime, and piperacillin/tazobactam may be considered. PMID- 24239066 TI - Modeling fish biological responses to contaminants and natural variability in estuaries. AB - Understanding the factors that influence biological responses to contaminants has long been a major goal in marine environmental research. Seven estuarine sites along the Portuguese coast were sampled over a year, and different biological responses of Pomatoschistus microps and Atherina presbyter were determined: superoxide dismutase, catalase, ethoxyresorufin O-deethylase, glutathione S transferase, metallothioneins, lipid peroxidation, RNA:DNA ratio and condition factor K. Generalized linear models (GLM) were developed for each biological variable per species in relation to sediment chemical characterization (metals and polycyclic aromatic hydrocarbons concentration) and environmental conditions (month, site, water temperature, salinity, depth and mud percentage in the sediment). GLM varied in explanatory power and in the set of predictor variables included in the models. Environmental factors were frequently selected as predictor variables. Individual metals concentration and sediment quality guidelines (integrating all metals) were the major contaminants explaining biological variability. Accordingly, models for metallothioneins and lipid peroxidation had highest explanatory power. Species-specific responses and dataset size were the basis of observed differences between GLM for the two species. PMID- 24239067 TI - Negative effects of ocean acidification on two crustose coralline species using genetically homogeneous samples. AB - We evaluated acidification effects on two crustose coralline algal species common to Pacific coral reefs, Lithophyllum kotschyanum and Hydrolithon samoense. We used genetically homogeneous samples of both species to eliminate misidentification of species. The growth rates and percent calcification of the walls of the epithallial cells (thallus surface cells) of both species decreased with increasing pCO2. However, elevated pCO2 more strongly inhibited the growth of L. kotschyanum versus H. samoense. The trend of decreasing percent calcification of the cell wall did not differ between these species, although intercellular calcification of the epithallial cells in L. kotschyanum was apparently reduced at elevated pCO2, a result that might indicate that there are differences in the solubility or density of the calcite skeletons of these two species. These results can provide knowledge fundamental to future studies of the physiological and genetic mechanisms that underlie the response of crustose coralline algae to environmental stresses. PMID- 24239068 TI - Stigmatization of people with drug dependence in China: a community-based study in Hunan province. AB - BACKGROUND: Drug abuse remains a serious problem in China, and has become a major threat to public health and social security. Since the issuance and enforcement of the new Anti-Drug law in 2008, the community has become the primary site for drug rehabilitation. However, the attitudes of members in community toward the people with drug use disorders are unclear. METHODS: A random sample of household respondents was studied in two communities in Hunan province in China. A total of 848 individuals participated (response rate 83.7%). Respondents initially were asked a set of questions about their knowledge about dug dependence, and then were randomly assigned to 1 of 4 vignette conditions. Three vignettes described different type of drug dependence meeting diagnostic criteria, and the fourth depicted a "normal person." RESULTS: Poor knowledge of drug dependence was common. Negative attitudes towards drug dependent people were widespread. Most respondents believed that drug dependence was caused by the person's own weak will (82.0%) and own hedonistic lifestyle (81.3%), and should be punished as illegal behavior (80.4%). The vast majority labeled the person with drug dependence as an addict, rated them as having undesirable characteristics, and expressed a strong desire for social distance. There were few socio-demographic predictors of both poor knowledge and negative attitudes. CONCLUSIONS: A community-based rehabilitation program in China should take into account the widespread stigmatization of people with drug dependence. PMID- 24239069 TI - Factors influencing dairy calf and replacement heifer mortality in France. AB - Herd-level risk factors for dairy calf and heifer mortality in France were identified by calculating herd-level variables (including mortality risk or rate) using the National Bovine Identification Database (2005 and 2006). Eleven dairy production areas representing different livestock systems were also included. Statistical analyses were based on a probit model (mortality risk or rate=0 or >0) and a linear model (mortality risk or rate >0) corrected by the sample bias Heckman method. The same associations were reported for 2005 and 2006. The mortality risks or rates for calves and heifers were positively associated with the proportion of purchased cows or being a Milk Control Program member and negatively associated with adhering to the Good Breeding Practices charter and having an autumn calving peak. The associations between mortality and the breeds or the production areas were positive or negative, depending on the classes of animal. Mortality and having a beef herd in addition to the dairy herd were negatively associated for noncrossed birth to 2-d-old calves, noncrossed 3-d- to 1-mo-old calves, and 3-d- to 1-mo-old heifers. Having a beef herd probably provides specific know-how related to newborn and young calf management that makes it easier to attain low mortality in pure-breed dairy calves. The proportion of males born was positively associated with mortality for the birth to 2-d-old calves (all classes) and for the 3-d- to 1-mo-old beef-crossed calves, but negatively for all classes of heifers. This indicates that heifer management was improved when the availability of newborn heifers decreased, resulting in low mortality. This lower mortality is apparent for all classes of heifers present on the farm during the year when the proportion of males was low, and demonstrates an anticipatory effect. In conclusion, this study shows that the presence of a beef herd in addition to the dairy herd within a farm is associated with decreased dairy calf mortality. It also shows that heifer mortality decreases when the proportion of heifers born decreased. These determinants of dairy calf and heifer mortality are of great importance for farmer advisors, the dairy industry, and the political decision makers. PMID- 24239070 TI - Short communication: Aflatoxin M1 in dairy products sold in Sanliurfa, Turkey. AB - The aim of this study was to detect the presence of aflatoxin M1 (AFM1) in samples of raw milk (n=38), UHT milk (n=12), white pickled cheese (n=50), and yogurt (n=50) collected from the Sanliurfa city markets and locally produced dairy products by ELISA. The mean contamination rates were 56.74 +/- 40.32, 43.1 +/- 23.19, 103.2 +/- 29.13, and 55.28 +/- 12.68 ng/kg, respectively, for raw milk, UHT milk, white pickled cheese, and yogurt. According to the data, 21 (55%) raw milk, 3 (25%) UHT milk, 10 (20%) white pickled cheese, and 10 (20%) yogurt samples were contaminated with AFM1 over the acceptable levels (>=50 ng/kg), ranging from 0.82 to 130.89 ng/kg. None of the white pickled cheese samples contained AFM1 levels above the Turkish legal limit (250 ng/kg). Consequently, the AFM1 contamination levels determined in this study in white pickled cheese were not considered to pose a serious public health hazard. However, the AFM1 levels in raw and UHT milk and yogurt samples indicate an increased human health risk in Turkey related to high aflatoxin levels. Therefore, milk and dairy products have to be monitored by the Turkish public health authorities continuously to detect AFM1 contamination. PMID- 24239071 TI - Short communication: Antimicrobial resistance and virulence characterization of methicillin-resistant staphylococci isolates from bovine mastitis cases in Portugal. AB - Methicillin-resistant staphylococci (MRS) have already been reported as mastitis agents. Such bacterial species are a public health concern, and the characterization of their antimicrobial resistance and virulence profile is important to better control their dissemination. The present work evaluated the distribution of methicillin-resistance among 204 staphylococci from clinical (n=50) and subclinical (n=154) bovine mastitis. The presence ofthe mecA gene was determined by PCR. Phenotypic expression of coagulase, DNase, lipase, gelatinase, hemolytic enzymes, and biofilm production was evaluated. The presence of biofilm related genes, icaA, icaD, and bap, was also determined. Antimicrobial resistance patterns for aminoglycosides, lincosamides, macrolides, fluoroquinolones, sulphonamides, tetracyclines, and fusidic acid were determined. Nineteen (9.3%) isolates were identified as MRS, and the presence of mecA in these isolates was confirmed by PCR. Virulence factors evaluation revealed that gelatinase was the most frequently detected (94.7%), followed by hemolysins (73.7%) and lipase (68.4%); 84.2% of the MRS isolates produced biofilm and icaA and icaD were detected in almost half of the MRS isolates (52.6%), but all were bap-negative. Resistance against other antimicrobial agents ranged from 0 (fusidic acid, ciprofloxacin, norfloxacin, enrofloxacin) to 100% (nalidixic acid). Resistance to nalidixic acid and nalidixic acid-tetracycline were the most common antimicrobial resistance profiles (31.6%). This study confirms that despite the low prevalence of MRS, isolates frequently express other virulence traits, especially biofilm, that may represent a serious challenge to clinicians. PMID- 24239072 TI - Climatic effects on milk production traits and somatic cell score in lactating Holstein-Friesian cows in different housing systems. AB - The objective of this study was to compare the effect of the temperature-humidity index (THI) on milk production traits and somatic cell score (SCS) of dairy cows raised in 4 different housing systems: (1) warm loose housing with access to grazing (WG), (2) warm loose housing without access to grazing (WI), (3) cold loose housing with access to grazing (CG), and (4) cold loose housing without access to grazing (CI). For each of the 4 housing systems, 5 farms with a herd size of 70 to 200 lactating cows in Lower Saxony, Germany, were studied. Ambient temperature and relative humidity were recorded hourly in each barn to calculate THI. Milk production data included 21,546 test-day records for milk, fat, and protein yield, and SCS. These data were associated with the average THI of the 3 d preceding the respective measurement, which was divided into 6 classes (<45, >=45 to <50, >=50 to <55, >=55 to <60, >=60 to <65, and >=65). Furthermore, bulk milk samples including the fat and protein percentage, and SCS taken 4 to 6 times per month were associated with the average and maximum THI of the 3 d before sampling. Data were recorded from April 2010 to March 2011. In each of the housing systems, monthly THI values above 60, indicating heat stress, were recorded between June and September, with higher values in WI and WG. In all systems, fat-corrected milk, fat, and protein yields of the test-day records decreased in tendency from 60 <= THI<65 to THI >65. In WI and CI, values for SCS were greater in the class THI > 65 than in 60 <= THI<65, whereas no difference between any of the THI classes was found in WG and CG. The fat and protein percentage of the bulk milk samples decreased with increasing 3-d maximum THI in all 4 systems, whereas the SCS increased with increasing 3-d average THI. In conclusion, negative effects of heat stress conditions under a temperate climate on milk production traits and SCS were found, although a housing system being superior to the other systems in altering heat stress effects was not identified. PMID- 24239073 TI - Use of sodium polyphosphates with different linear lengths in the production of spreadable processed cheese. AB - The objective of this study was to describe the dependence of textural properties (hardness, cohesiveness, and relative adhesiveness) of processed cheese spreads on the proportion of disodium phosphate (DSP), tetrasodium diphosphate (TSPP), and sodium salts of polyphosphate in ternary mixtures of emulsifying salts. Sodium salts of polyphosphate with different mean lengths (n ~ 5, 9, 13, 20, and 28) were used. Pentasodium triphosphate (PSTP) was used instead of TSPP in the second part of the study. Products with and without pH adjustment were tested (the target pH value was 5.60-5.80). Textural properties of the processed cheese were observed after 2, 9, and 30 d of storage at 6 degrees C. Hardness of the processed cheese with a low content of polyphosphate increased at a specific DSP:TSPP ratio (~1:1 to 3:4). This trend was the same for all the polyphosphates used; only the absolute values of texture parameters were different. The same trends were observed in the ternary mixtures with PSTP, showing lower final values of hardness compared with samples containing TSPP. Hardness and cohesiveness decreased and relative adhesiveness increased in the samples with increased pH values and vice versa; the main trend remained unchanged. PMID- 24239074 TI - Short communication: Effect of active food packaging materials on fluid milk quality and shelf life. AB - Active packaging, in which active agents are embedded into or on the surface of food packaging materials, can enhance the nutritive value, economics, and stability of food, as well as enable in-package processing. In one embodiment of active food packaging, lactase was covalently immobilized onto packaging films for in-package lactose hydrolysis. In prior work, lactase was covalently bound to low-density polyethylene using polyethyleneimine and glutaraldehyde cross-linkers to form the packaging film. Because of the potential contaminants of proteases, lipases, and spoilage organisms in typical enzyme preparations, the goal of the current work was to determine the effect of immobilized-lactase active packaging technology on unanticipated side effects, such as shortened shelf-life and reduced product quality. Results suggested no evidence of lipase or protease activity on the active packaging films, indicating that such active packaging films could enable in-package lactose hydrolysis without adversely affecting product quality in terms of dairy protein or lipid stability. Storage stability studies indicated that lactase did not migrate from the film over a 49-d period, and that dry storage resulted in 13.41% retained activity, whereas wet storage conditions enabled retention of 62.52% activity. Results of a standard plate count indicated that the film modification reagents introduced minor microbial contamination; however, the microbial population remained under the 20,000 cfu/mL limit through the manufacturer's suggested 14-d storage period for all film samples. This suggests that commercially produced immobilized lactase active packaging should use purified cross-linkers and enzymes. Characterization of unanticipated effects of active packaging on food quality reported here is important in demonstrating the commercial potential of such technologies. PMID- 24239075 TI - Moist and dry heating-induced changes in protein molecular structure, protein subfractions, and nutrient profiles in camelina seeds. AB - The objectives of the present study were to investigate the nutritive value of camelina seeds (Camelina sativa L. Crantz) in ruminant nutrition and to use molecular spectroscopy as a novel technique to quantify the heat-induced changes in protein molecular structures in relation to protein digestive behavior in the rumen and intestine of dairy cattle. In this study, camelina seeds were used as a model for feed protein. The seeds were kept as raw (control) or heated in an autoclave (moist heating) or in an air-draft oven (dry heating) at 120 degrees C for 60 min. The parameters evaluated were (1) chemical profiles, (2) Cornell Net Protein and Carbohydrate System protein subfractions, (3) nutrient digestibilities and estimated energy values, (4) in situ rumen degradation and intestinal digestibility, and (5) protein molecular structures. Compared with raw seeds, moist heating markedly decreased (52.73 to 20.41%) the content of soluble protein and increased (2.00 to 9.01%) the content of neutral detergent insoluble protein in total crude protein (CP). Subsequently, the rapidly degradable Cornell Net Protein and Carbohydrate System CP fraction markedly decreased (45.06 to 16.69% CP), with a concomitant increase in the intermediately degradable (45.28 to 74.02% CP) and slowly degradable (1.13 to 8.02% CP) fractions, demonstrating a decrease in overall protein degradability in the rumen. The in situ rumen incubation study revealed that moist heating decreased (75.45 to 57.92%) rumen degradable protein and increased (43.90 to 82.95%) intestinal digestibility of rumen-undegradable protein. The molecular spectroscopy study revealed that moist heating increased the amide I-to-amide II ratio and decreased alpha-helix and alpha-helix-to-beta-sheet ratio. In contrast, dry heating did not significantly change CP solubility, rumen degradability, intestinal digestibility, and protein molecular structures compared with the raw seeds. Our results indicated that, compared with dry heating, moist heating markedly changed protein chemical profiles, protein subfractions, rumen protein degradability, and intestinal digestibility, which were associated with changes in protein molecular structures (amide I-to-amid II ratio and alpha-helix-to-beta-sheet ratio). Moist heating improved the nutritive value and utilization of protein in camelina seeds compared with dry heating. PMID- 24239076 TI - Genomic selection strategies in a small dairy cattle population evaluated for genetic gain and profit. AB - The objective of this study was to evaluate a genomic breeding scheme in a small dairy cattle population that was intermediate in terms of using both young bulls (YB) and progeny-tested bulls (PB). This scheme was compared with a conventional progeny testing program without use of genomic information and, as the extreme case, a juvenile scheme with genomic information, where all bulls were used before progeny information was available. The population structure, cost, and breeding plan parameters were chosen to reflect the Danish Jersey cattle population, being representative for a small dairy cattle population. The population consisted of 68,000 registered cows. Annually, 1,500 bull dams were screened to produce the 500 genotyped bull calves from which 60 YB were selected to be progeny tested. Two unfavorably correlated traits were included in the breeding goal, a production trait (h(2)=0.30) and a functional trait (h(2)=0.04). An increase in reliability of 5 percentage points for each trait was used in the default genomic scenario. A deterministic approach was used to model the different breeding programs, where the primary evaluation criterion was annual monetary genetic gain (AMGG). Discounted profit was used as an indicator of the economic outcome. We investigated the effect of varying the following parameters: (1) increase in reliability due to genomic information, (2) number of genotyped bull calves, (3) proportion of bull dam sires that are young bulls, and (4) proportion of cow sires that are young bulls. The genomic breeding scheme was both genetically and economically superior to the conventional breeding scheme, even in a small dairy cattle population where genomic information causes a relatively low increase in reliability of breeding values. Assuming low reliabilities of genomic predictions, the optimal breeding scheme according to AMGG was characterized by mixed use of YB and PB as bull sires. Exclusive use of YB for production cows increased AMGG up to 3 percentage points. The results from this study supported our hypothesis that strong interaction effects exist. The strongest interaction effects were obtained between increased reliabilities of genomic estimated breeding values and more intensive use of YB. The juvenile scheme was genetically inferior when the increase in reliability was low (5 percentage points), but became genetically superior at higher reliabilities of genomic estimated breeding values. The juvenile scheme was always superior according to discounted profit because of the shorter generation interval and minimizing costs for housing and feeding waiting bulls. PMID- 24239077 TI - Combined effect of active coating and modified atmosphere packaging on prolonging the shelf life of low-moisture Mozzarella cheese. AB - In this work, the effect of active coating on the shelf life of low-moisture Mozzarella cheese packaged in air and modified atmosphere (MAP) was studied. The active coating was based on sodium alginate (2%, wt/vol) and potassium sorbate (1%, wt/vol). The MAP was made up of 75% CO2 and 25% N2 (MAP1), 25% CO2 and 75% N2 (MAP2), or 50% CO2 and 50% N2 (MAP3). The product quality decay was assessed by monitoring microbiological and sensory changes during storage at 4, 8, and 14 degrees C. Results showed that the combination of active coating and MAP was able to improve the preservation of low-moisture Mozzarella cheese. Specifically, the shelf life increased up to 160 d for samples stored at 4 degrees C, and 40 and 11 d for those at 8 and 14 degrees C, respectively. A faster quality decay for untreated samples packaged in air was observed. In particular, the Pseudomonas spp. growth and the appearance of molds were responsible for product unacceptability. The combination of active coating and MAP represents a strategic solution to prolong the shelf life of low-moisture Mozzarella cheese and to ensure the safety of the product under thermal abuse conditions. PMID- 24239078 TI - Goat milk consumption modulates liver divalent metal transporter 1 (DMT1) expression and serum hepcidin during Fe repletion in Fe-deficiency anemia. AB - Iron deficiency is the most prevalent micronutrient deficiency worldwide. In spite of the crucial role of hepatocyte divalent metal transporter 1 (DMT1) and hepcidin in Fe metabolism, to date, no studies have directly tested the role of these proteins in liver Fe metabolism during Fe repletion after induced Fe deficiency anemia. Therefore, the aim of the current study was to assess the effect of goat or cow milk-based diets on Fe metabolism in one of the main body storage organs, the liver, during the course of Fe repletion with goat or cow milk-based diets in anemic rats. Animals were placed on a preexperimental period of 40 d, a control group receiving a normal-Fe diet and the Fe-deficient group receiving a low-Fe diet (5 mg of Fe/kg of diet). Rats were fed for 30 d with goat or cow milk-based diets with normal Fe content (45 mg of Fe/kg of diet). The hematological parameters, serum hepcidin, hepatosomatic index, liver Fe content, and liver DMT1 expression were determined. During the recovery of the anemia with milk-based diets, the restoration of liver Fe content and hematological parameters, especially with goat milk, increased the red blood cell count, favoring the oxygen supply and weight gain. Moreover, goat milk consumption potentiates liver DMT1 expression, enhancing Fe metabolism and storage. In addition, the increase in serum hepcidin in anemic rats observed in the current study also explains and supports the higher liver Fe content after supplying goat milk, because it blocks the liberation of Fe from hepatocytes, increasing its storage in liver. PMID- 24239079 TI - Effect of supplementing fat to pregnant nonlactating cows on colostral fatty acid profile and passive immunity of the newborn calf. AB - The objectives were to evaluate the effect of supplementing saturated or unsaturated long-chain fatty acids (FA) to nulliparous and parous Holstein animals (n=78) during late gestation on FA profile of colostrum and plasma of newborn calves and on production and absorption of IgG. The saturated FA supplement (SAT) was enriched in C18:0 and the unsaturated FA supplement (ESS) was enriched in the essential FA C18:2n-6. Fatty acids were supplemented at 1.7% of dietary dry matter to low-FA diets (1.9% of dietary dry matter) during the last 8 wk of gestation. Calves were fed 4 L of colostrum within 2h of birth from their own dam or from a dam fed the same treatment. Feeding fat did not affect prepartum dry matter intake, body weight change, or gestation length. Parous but not nulliparous dams tended to give birth to heavier calves if fed fat prepartum. Parous dams were less able to synthesize essential FA derivatives, as evidenced by lower desaturase indices, compared with nulliparous dams, suggesting a greater need for essential FA supplementation. The FA profile of colostrum was modified to a greater degree by prepartum fat feeding than was that of neonatal calf plasma. The placental transfer and synthesis of elongated n-3 FA (C20:5, C22:5, and C22:6) were reduced, whereas the n-6 FA (C18:2, C18:3, and C20:3) were increased in plasma of calves born from dams fed ESS rather than SAT. Supplementing unsaturated FA prepartum resulted in elevated concentrations of trans isomers of unsaturated monoene and diene FA, as well as C18:2n-6 in colostrum. Serum concentrations of IgG tended to be increased in calves born from dams fed fat compared with those not fed fat, and prepartum feeding of SAT tended to improve circulating concentrations of IgG in newborn calves above the feeding of ESS. Apparent efficiency of absorption of IgG was improved in calves born from dams fed fat, and SAT supplementation appeared more effective than supplementation with ESS. Feeding SAT prepartum may be of greater benefit based upon greater circulating IgG concentrations of calves after colostrum feeding. Feeding moderate amounts of saturated or unsaturated long-chain FA during the last 8 wk of gestation changed the FA profile of colostrum and plasma of neonates to reflect that of the supplements. PMID- 24239080 TI - Induced hyperketonemia affects the mammary immune response during lipopolysaccharide challenge in dairy cows. AB - Metabolic adaptations during negative energy and nutrient balance in dairy cows are thought to cause impaired immune function and hence increased risk of infectious diseases, including mastitis. Characteristic adaptations mostly occurring in early lactation are an elevation of plasma ketone bodies and free fatty acids (nonesterified fatty acids, NEFA) and diminished glucose concentration. The aim of this study was to investigate effects of elevated plasma beta-hydroxybutyrate (BHBA) at simultaneously even or positive energy balance and thus normal plasma NEFA and glucose on factors related to the immune system in liver and mammary gland of dairy cows. In addition, we investigated the effect of elevated plasma BHBA and intramammary lipopolysaccharide (LPS) challenge on the mammary immune response. Thirteen dairy cows were infused either with BHBA (HyperB, n=5) to induce hyperketonemia (1.7 mmol/L) or with a 0.9% saline solution (NaCl, n=8) for 56 h. Two udder quarters were injected with 200 MUg of LPS after 48 h of infusion. Rectal temperature (RT) and somatic cell counts (SCC) were measured before, at 48 h after the start of infusions, and hourly during the LPS challenge. The mRNA abundance of factors related to the immune system was measured in hepatic and mammary tissue biopsies 1 wk before and 48 h after the start of the infusion, and additionally in mammary tissue at 56 h of infusion (8h after LPS administration). At 48 h of infusion in HyperB, the mRNA abundance of serum amyloid A (SAA) in the mammary gland was increased and that of haptoglobin (Hp) tended to be increased. Rectal temperature, SCC, and mRNA abundance of candidate genes in the liver were not affected by the BHBA infusion until 48 h. During the following LPS challenge, RT and SCC increased in both groups. However, SCC increased less in HyperB than in NaCl. Quarters infused with LPS showed a more pronounced increase of mRNA abundance of IL-8 and IL-10 in HyperB than in NaCl. The results demonstrate that an increase of plasma BHBA upregulates acute phase proteins in the mammary gland. In response to intramammary LPS challenge, elevated BHBA diminishes the influx of leukocytes from blood into milk, perhaps by via modified cytokine synthesis. Results indicate that increased ketone body plasma concentrations may play a crucial role in the higher mastitis susceptibility in early lactation. PMID- 24239081 TI - Microbiological safety and quality of Mozzarella cheese assessed by the microbiological survey method. AB - Dairy products are characterized by reduced shelf life because they are an excellent growth medium for a wide range of microorganisms. For this reason, it is important to monitor the microbiological quality of dairy products and, in particular, the total viable count and concentration of Escherichia coli, as they are indicators of the hygienic state of these products. In addition, in dairy products such as Mozzarella cheese, it is important to monitor the concentration of lactic acid bacteria (LAB), as they are the major components of starter cultures used in cheese production, contributing to the taste and texture of fermented products and inhibiting food spoilage bacteria by producing growth inhibiting substances. For these reasons, to ensure the quality and safety of their products, cheese makers should monitor frequently, during fresh cheese production, the concentration of LAB and spoilage bacteria. However, usually, small- to medium-size dairy factories do not have an internal microbiological laboratory and external laboratories of analysis are often too expensive and require several days for the results. Compared with traditional methods, the microbiological survey (MBS) method developed by Roma Tre University (Rome, Italy) allows faster and less-expensive microbiological analyses to be conducted wherever they are necessary, without the need for a microbiological laboratory or any instrumentation other than MBS vials and a thermostat. In this paper, we report the primary validation of the MBS method to monitor LAB concentration in Mozzarella cheese and the analysis, using the MBS method, of total viable count, E. coli, and LAB concentrations in the production line of Mozzarella cheese as well as during the shelf life of the product stored at 20 degrees C. The results obtained indicate that the MBS method may be successfully used by small- to medium-size dairy factories that do not have an internal microbiological laboratory. Using the MBS method, these dairy factories can monitor autonomously the microbiological safety and quality of their products, saving both time and money. PMID- 24239083 TI - The effect of 2 liquid feeds and 2 sources of protein in starter on performance and blood metabolites in Holstein neonatal calves. AB - The aim of present study was to investigate the effect of 2 liquid feeds and 2 protein sources in starter on the performance and blood metabolite responses of Holstein neonatal calves from birth to 6 wk of age. Calves (20 males and 20 females) based on sex were randomly assigned to 4 treatments in a 2 * 2 * 2 factorial arrangement, including soybean meal (SBM) and meat and bone meal (MB) with either fermented colostrum (or fresh milk. Although sex and liquid feed had no significant effect on feed intake, calves consumed more feed intake on the diet containing SBM (15 +/- 0.2 kg) than MB (13 +/- 0.2 kg) during the experimental period; also, weight gain was affected by both liquid feed and starter. Liquid feed and starter had significant effects on calf body size, including pin width, hip width, withers height, hip height, and stomach size, but no significant effects were observed on calf body size between the sexes. Plasma glucose concentration was not affected by sex, liquid feed, or starter. Plasma urea nitrogen concentration decreased in the first 3 wk and then started to increase during the last 3 wk, but it was only affected by starter and calves receiving SBM (10.18 mg/dL) had a higher concentration of plasma urea nitrogen than calves receiving MB (9.6 mg/dL) at the end of the experiment. Plasma growth hormone and insulin-like growth factor I concentrations decreased in all treatment groups from d 0 to the end of the study. No significant effects were observed on plasma growth hormone and insulin-like growth factor I concentrations between the 2 sexes, but they were significantly affected by both liquid feed and starter. Results of the present study provide useful information to apply to Holstein neonatal calves during the first 6 wk of life when liquid feed and 2 sources of protein in starter are considered. PMID- 24239082 TI - Short communication: Genetic characterization of digital cushion thickness. AB - Dairy cow lameness is a serious animal welfare issue. It is also a significant cause of economic losses, reducing reproductive efficiency and milk production and increasing culling rates. The digital cushion is a complex structure composed mostly of adipose tissue located underneath the distal phalanx and has recently been phenotypically associated with incidence of claw horn disruption lesions (CHDL); namely, sole ulcers and white line disease. The objective of this study was to characterize digital cushion thickness genetically and to investigate its association with body condition score (BCS), locomotion score (LOCO), CHDL, and milk production. Data were collected from 1 large closely monitored commercial dairy farm located in upstate New York; 923 dairy cows were used. Before trimming, the following data were collected by a member of the research team: BCS, cow height measurement, and LOCO. Presence or not of CHDL (sole ulcer or white line disease, or both) was recorded at trimming. Immediately after the cows were hoof trimmed, they underwent digital sonographic B-mode examination for the measurement of digital cushion thickness. Factors such as parity number, stage of lactation, calving date, mature-equivalent 305-d milk yield (ME305MY), and pedigree information were obtained from the farm's dairy management software (DairyCOMP 305; Valley Agricultural Software, Tulare, CA). Univariate animal models were used to obtain variance component estimations for each studied trait (CHDL, BCS, digital cushion thickness average, LOCO, height, and ME305MY) and a 6 variate analysis was conducted to estimate the genetic, residual, and phenotypic correlations between the studied traits. The heritability estimate of DCTA was 0.33+/-0.09, whereas a statistically significant genetic correlation was estimated between DCTA and CHDL (-0.60+/-0.29). Of the other genetic correlations, significant estimates were derived for BCS with LOCO (-0.49+/-0.19) and ME305MY (-0.48+/-0.20). Digital cushion thickness is moderately heritable and genetically strongly correlated with CHDL. PMID- 24239084 TI - Effect of camel chymosin on the texture, functionality, and sensory properties of low-moisture, part-skim Mozzarella cheese. AB - The objective of this study was to compare the effect of coagulant (bovine calf chymosin, BCC, or camel chymosin, CC), on the functional and sensory properties and performance shelf-life of low-moisture, part-skim (LMPS) Mozzarella. Both chymosins were used at 2 levels [0.05 and 0.037 international milk clotting units (IMCU)/mL], and clotting temperature was varied to achieve similar gelation times for each treatment (as this also affects cheese properties). Functionality was assessed at various cheese ages using dynamic low-amplitude oscillatory rheology and performance of baked cheese on pizza. Cheese composition was not significantly different between treatments. The level of total calcium or insoluble (INSOL) calcium did not differ significantly among the cheeses initially or during ripening. Proteolysis in cheese made with BCC was higher than in cheeses made with CC. At 84 d of ripening, maximum loss tangent values were not significantly different in the cheeses, suggesting that these cheeses had similar melt characteristics. After 14 d of cheese ripening, the crossover temperature (loss tangent = 1 or melting temperature) was higher when CC was used as coagulant. This was due to lower proteolysis in the CC cheeses compared with those made with BCC because the pH and INSOL calcium levels were similar in all cheeses. Cheeses made with CC maintained higher hardness values over 84 d of ripening compared with BCC and maintained higher sensory firmness values and adhesiveness of mass scores during ripening. When melted on pizzas, cheese made with CC had lower blister quantity and the cheeses were firmer and chewier. Because the 2 types of cheeses had similar moisture contents, pH values, and INSOL Ca levels, differences in proteolysis were responsible for the firmer and chewier texture of CC cheeses. When cheese performance on baked pizza was analyzed, properties such as blister quantity, strand thickness, hardness, and chewiness were maintained for a longer ripening time than cheeses made with BCC, indicating that use of CC could help to extend the performance shelf-life of LMPS Mozzarella. PMID- 24239085 TI - Short communication: Validation of genomic breeding value predictions for feed intake and feed efficiency traits. AB - Validating genomic prediction equations in independent populations is an important part of evaluating genomic selection. Published genomic predictions from 2 studies on (1) residual feed intake and (2) dry matter intake (DMI) were validated in a cohort of 78 multiparous Holsteins from Australia. The mean realized accuracy of genomic prediction for residual feed intake was 0.27 when the reference population included phenotypes from 939 New Zealand and 843 Australian growing heifers (aged 5-8 mo) genotyped on high density (770k) single nucleotide polymorphism chips. The 90% bootstrapped confidence interval of this estimate was between 0.16 and 0.36. The mean realized accuracy was slightly lower (0.25) when the reference population comprised only Australian growing heifers. Higher realized accuracies were achieved for DMI in the same validation population and using a multicountry model that included 958 lactating cows from the Netherlands and United Kingdom in addition to 843 growing heifers from Australia. The multicountry analysis for DMI generated 3 sets of genomic predictions for validation animals, one on each country scale. The highest mean accuracy (0.72) was obtained when the genomic breeding values were expressed on the Dutch scale. Although the validation population used in this study was small (n=78), the results illustrate that genomic selection for DMI and residual feed intake is feasible. Multicountry collaboration in the area of dairy cow feed efficiency is the evident pathway to achieving reasonable genomic prediction accuracies for these valuable traits. PMID- 24239086 TI - Molecular epidemiology of recurrent clinical mastitis due to Streptococcus uberis: evidence of both an environmental source and recurring infection with the same strain. AB - This study was undertaken because clinicians and farmers have observed that a considerable number of cows diagnosed with Streptococcus uberis mastitis have recurrences of mastitis in the same or a different quarter. The study was an attempt to answer whether these recurring cases were due to treatment failure (in which case a search would have begun for a better treatment for Strep. uberis mastitis) or due to reinfection with a different strain of Strep. uberis. Using pulsed-field gel electrophoresis (PFGE), we determined that the majority of recurrences (20 of 27) were caused by a new strain of Strep. uberis, indicating that treatment of the initial infection had been successful. A small number of recurrences (5 of 27) were caused by the initial strain, indicating persistence. The remaining 2 recurrences occurred in a new quarter but with the initial strain of Strep. uberis, indicating either spread between quarters or reactivation of a previous subclinical infection. Analysis of the PFGE profiles failed to reveal any strain-specific propensity to persist, because strains causing recurrences occurred in most of the major clusters. PMID- 24239087 TI - Evaluation of effects of metritis management in a complex dairy herd health management program. AB - Evaluating the effects of all interventions in a dairy herd, including the effects of various herd health management programs (HHMP), is highly relevant. A traditional randomized controlled trial is the gold standard but is likely practically impossible or prohibitively expensive to use for a general evaluation of a HHMP. Generalizability may also be poor because of the dynamics of the production contexts. In this study, we demonstrate an approach for evaluating the effects of an HHMP in the field, specifying an intervention theory for an ongoing HHMP in the context of the Danish dairy industry. As an example, we suggest one coherent analytical approach for studying the possible effects on milk production of systematic postpartum examinations of vaginal discharge, which is supposed to improve detection and treatment of metritis or endometritis. This routine is one component of the HHMP. The data consisted of 121 herds and 76,953 lactations over a 15-yr period. For parity group 1, the negative effects of metritis (despite treatment) on 305-d milk production after a normal calving were reduced by 116 kg of energy-corrected milk after enrollment in the HHMP. For parity group 2 and parity group >2, enrollment in the HHMP resulted in a 129-kg and an 80-kg energy corrected milk yield increase in milk production, respectively. The results indicate that effects of the HHMP existed, which were mediated through improved metritis detection. This study demonstrates the importance of a clear-cut intervention theory, although even with a theory, the research question can be too herd and context specific. In such a case, a within-herd randomized controlled trial study design seems to be the only way to achieve a valid result for a given herd, and acquiring valid results from an observational multi-herd study will be very difficult. PMID- 24239088 TI - Evaluation of milk ELISA for detection of Mycobacterium avium subspecies paratuberculosis in dairy herds and association with within-herd prevalence. AB - Cow-level milk ELISA results can be used to determine herd Mycobacterium avium ssp. paratuberculosis (MAP) status. Milk sample collection is minimally invasive and ELISA results can be obtained quickly and economically. The objectives were to evaluate the herd-level test characteristics of 3 commercial milk ELISA, and to determine the impact of within-herd MAP prevalence on the performance of the milk ELISA herd test. A total of 32 purposively selected herds with a median herd size of 66 milking cows were used in this 2-yr project. Fecal and milk samples were collected from all milking cows at 6-mo intervals. Fecal samples were pooled by cow age, with 5 cow samples per pool; individual fecal culture was completed on cow samples from positive pools. Herd MAP status was defined as MAP positive if, at any point during the longitudinal study, a pooled fecal culture from the herd was positive. Milk samples were analyzed using each of 3 commercial milk ELISA kits; a cow-level result from each ELISA was classified as positive following the respective manufacturer's recommended threshold for a positive result. Herd-level milk ELISA test characteristics were estimated using generalized estimating equations logistic models, which accounted for repeated measurements. Using a cutoff of 2% milk ELISA-positive cows, milk ELISA herd sensitivity relative to a herd MAP status based on all pooled fecal culture results collected during the study was as follows: ELISA A: 59% [95% confidence interval (CI): 36-78%), ELISA B: 56% (95% CI: 32-77%), and ELISA C: 63% (95% CI: 41-81%). Herd specificity for ELISA A, B, and C was 80% (95% CI: 71-88%), 96% (95% CI: 89-98%), and 92% (95% CI: 86-96%), respectively. The remainder of the analyses focused on results from ELISA B. Herd sensitivity of ELISA B increased as MAP prevalence increased. In herds with a mean MAP prevalence <=5%, the herd sensitivity of the milk ELISA was low, ranging from 11% when MAP prevalence was 1%, to 62% when MAP prevalence was 5%. Categorical likelihood ratios based on milk ELISA within-herd prevalence predicted that herds with milk ELISA prevalence above 0 but <2% had a similar likelihood to be MAP positive or MAP negative, whereas herds with a milk ELISA prevalence between 2 and 4% were 3.7 times more likely to be MAP positive than MAP negative. All herds with a milk ELISA prevalence >4% were MAP positive. Although milk ELISA B worked well to establish herd MAP status in high-prevalence herds, interpretation was unreliable in MAP negative and low-prevalence herds. PMID- 24239089 TI - Protein-protein interactions. PMID- 24239090 TI - Lifetime physical activity and cancer incidence--a cohort study of male former elite athletes in Finland. AB - OBJECTIVES: Physical activity has been shown to decrease the risk of certain cancers. Objective of this study was to assess the effect of physical activity on cancer incidence in former male athletes in older age. DESIGN: A cohort of 2448 elite male athletes and 1712 referents was followed-up for cancer incidence during 1986-2010 through the Finnish Cancer Registry. METHODS: Standardised incidence ratios were calculated with the general male population as the reference. Self-reported questionnaire-based data on covariates were used in Cox regression analyses comparing the risk of cancer in athletes and referents. RESULTS: The overall cancer incidence was lower in athletes than in the general population, standardised incidence ratio 0.89 (95% confidence interval 0.81 0.97). It was lowest among middle-distance runners (standardised incidence ratio 0.51, 95% confidence interval 0.22-1.01), long-distance runners (standardised incidence ratio 0.57, 95% confidence interval 0.35-0.88) and jumpers (standardised incidence ratio 0.60, 95% confidence interval 0.37-0.92). The standardised incidence ratio of lung cancer among athletes was 0.40 (95% confidence interval 0.27-0.55) and that of kidney cancer 0.23 (95% confidence interval 0.06-0.57). The hazard ratio for lung cancer between athletes and referents increased from the unadjusted ratio of 0.29 (95% confidence interval: 0.18-0.48) to 0.61 (95% confidence interval: 0.30-1.26) after adjustment for smoking status and pack-years of smoking. CONCLUSIONS: Former male elite athletes evidently have less cancer than men on the average. The lesser risk can be attributed to lifestyle factors, notably less frequent smoking among the athletes. PMID- 24239092 TI - Cinnamon polyphenols regulate S100beta, sirtuins, and neuroactive proteins in rat C6 glioma cells. AB - OBJECTIVE: Increasing evidence suggests that cinnamon has many health benefits when used in herbal medicine and as a dietary ingredient. The aim of this study was to investigate the effects of an aqueous extract of cinnamon, high in type A polyphenols, on molecular targets in rat C6 glioma cells that underlie their protective effects. METHODS: C6 rat glioma cells were seeded in 35-mm culture dishes or six-well plates, then were incubated with cinnamon polyphenols at doses of 10 and 20 MUg/mL for 24 h. The targeting protein expression, secretion, and phosphorylation were evaluated by immunoprecitation/immunoblotting and immunofluorescence imaging. RESULTS: Cinnamon polyphenols significantly enhanced secretion of S100beta, a Ca(2+)-binding protein, and increased intracellular S100beta expression after 24 h of incubation, in rat C6 glioma cells. Cinnamon polyphenols also enhanced protein levels of sirtuin 1, 2, and 3, deacetylases important in cell survival, and the tumor suppressor protein, p53, and inhibited the inflammatory factors, tumor necrosis factor alpha, and phospho-p65, a subunit of nuclear factor-kappabeta. Cinnamon polyphenols also up-regulated levels of phospho-p38, extracellular signal-regulated protein and mitogen-activated protein and kinase-activated protein kinases that may be important for prosurvival functions. CONCLUSION: Our results indicate that the effects of cinnamon polyphenols on upregulating prosurvival proteins, activating mitogen-activated protein kinase pathways, and decreasing proinflammatory cytokines may contribute to their neuroprotective effects. PMID- 24239091 TI - Crystal structure of Vdelta1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human gammadelta T cells. AB - The nature of the antigens recognized by gammadelta T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vdelta1 TCR-expressing gammadelta T cells, the major gammadelta lymphocyte population in epithelial tissues. We crystallized a Vdelta1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vdelta1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3delta residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vdelta1+ gammadelta T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by gammadelta T cells and reveal the prevalence of lipid recognition by innate-like T cell populations. PMID- 24239093 TI - Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia. AB - Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk. PMID- 24239094 TI - MRI diffusion tractography study in individuals with schizotypal features: a pilot study. AB - Diffusion tensor imaging (DTI) studies have identified changes in white matter tracts in schizophrenia patients and those at high risk of transition. Schizotypal samples represent a group on the schizophrenia continuum that share some aetiological risk factors but without the confounds of illness. The aim of the current study was to compare tract microstructural coherence as measured by fractional anisotropy (FA) between 12 psychometrically defined schizotypes and controls. We investigated bilaterally the uncinate and arcuate fasciculi (UF and AF) via a probabilistic tractography algorithm (PICo), with FA values compared between groups. Partial correlations were also examined between measures of subclinical hallucinatory/delusional experiences and FA values. Participants with schizotypal features were found to have increased FA values in the left hemisphere UF only. In the whole sample there was a positive correlation between FA values and measures of hallucinatory experience in the right AF. These findings suggest subtle changes in microstructural coherence are found in individuals with schizotypal features, but are not similar to changes predominantly observed in clinical samples. Correlations between mild hallucinatory experience and FA values could indicate increasing tract coherence could be associated with symptom formation. PMID- 24239096 TI - Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint. AB - PURPOSE: The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). MATERIALS AND METHODS: Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. RESULTS: The new bone regeneration was significantly greater in the PRP group (P < .011). Although the regeneration of the fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. CONCLUSIONS: PRP might enhance the regeneration of bone in TMJ-OA. PMID- 24239097 TI - Assessment of heavy metals/metalloid (As, Pb, Cd, Ni, Zn, Cr, Cu, Mn) concentrations in edible fish species tissue in the Pearl River Delta (PRD), China. AB - The major aim of this study was to investigate heavy metal content of edible fish in the PRD. Eleven species of fish (consisting of 711 individuals) [catfish (Clarias fuscus), tilapia (Oreochromis mossambicus), grass carp (Ctenopharyngodon idellus), bighead carp (Aristichthys nobilis), mandarin fish (Siniperca kneri), snakehead (Channa asiatiea), black bass (Micropterus salmoides), mangrove snapper (Lutjanus griseus), star snapper (Lutjanu stellatus), snubnose pompano (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides)] were collected for the analyses of heavy metals. Overall concentrations (mg/kg, ww) in the fish muscles were: As (0.03-1.53), Pb (0.03-8.62), Cd (0.02-0.06), Ni (0.44 9.75), Zn (15.7-29.5), Cr (0.22-0.65), Cu (0.79-2.26), Mn (0.82-6.91). Significant level of Pb were found in tilapia at all locations. It is recommended that heavy metal concentrations in different fish species must be determined on a regular basis in the future so as to reduce human health risks from acute and chronic food intoxication. PMID- 24239095 TI - Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancers: classification tree analysis. AB - PURPOSE: Although risk factors for squamous cell carcinoma of the esophagus and adenocarcinomas of the esophagus (EA), gastric cardia (GC), and other (noncardia) gastric (OG) sites have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancers. METHODS: We used classification tree analysis to analyze data from a population based case-control study (1095 cases, 687 controls) conducted in Connecticut, New Jersey, and western Washington State. RESULTS: Frequency of reported gastroesophageal reflux disease symptoms was the most important risk stratification factor for EA, GC, and OG, with dietary factors (EA, OG), smoking (EA, GC), wine intake (GC, OG), age (OG), and income (OG) appearing to modify the risk of these cancer sites. For esophageal squamous cell carcinoma, smoking was the most important risk stratification factor, with gastroesophageal reflux disease, income, race, noncitrus fruit, and energy intakes further modifying risk. CONCLUSION: Various combinations of risk factors appear to interact to affect risk of each cancer subtype. Replication of these data mining analyses are required before suggesting causal pathways; however, the classification tree results are useful in partitioning risk and mapping multilevel interactions among risk variables. PMID- 24239098 TI - Sperm swimming in the polychaete Galeolaria caespitosa shows substantial inter individual variability in response to future ocean acidification. AB - The rapidity of ocean acidification intensifies selection pressure for resilient phenotypes, particularly during sensitive early life stages. The scope for selection is greater in species with greater within-species variation in responses to changing environments, thus enhancing the potential for adaptation. We investigated among-male variation in sperm swimming responses (percent motility and swimming speeds) of the serpulid polychaete Galeolaria caespitosa to near- (DeltapH -0.3) and far-future ocean acidification (DeltapH -0.5). Responses of sperm swimming to acidification varied significantly among males and were overall negative. Robust sperm swimming behavior under near-future ocean acidification in some males may ameliorate climate change impacts, if traits associated with robustness are heritable, and thereby enhance the potential for adaptation to far-future conditions. Reduced sperm swimming in the majority of male G. caespitosa may decrease their fertilization success in a high CO2 future ocean. Resultant changes in offspring production could affect recruitment success and population fitness downstream. PMID- 24239099 TI - First treatment of a child suffering from severe ischemic cardiomyopathy with G CSF and sitagliptin. PMID- 24239101 TI - Study and optimization of the ultrasound-enhanced cleaning of an ultrafiltration ceramic membrane through a combined experimental-statistical approach. AB - Membrane fouling is one of the main drawbacks of ultrafiltration technology during the treatment of dye-containing effluents. Therefore, the optimization of the membrane cleaning procedure is essential to improve the overall efficiency. In this work, a study of the factors affecting the ultrasound-assisted cleaning of an ultrafiltration ceramic membrane fouled by dye particles was carried out. The effect of transmembrane pressure (0.5, 1.5, 2.5 bar), cross-flow velocity (1, 2, 3 ms(-1)), ultrasound power level (40%, 70%, 100%) and ultrasound frequency mode (37, 80 kHz and mixed wave) on the cleaning efficiency was evaluated. The lowest frequency showed better results, although the best cleaning performance was obtained using the mixed wave mode. A Box-Behnken Design was used to find the optimal conditions for the cleaning procedure through a response surface study. The optimal operating conditions leading to the maximum cleaning efficiency predicted (32.19%) were found to be 1.1 bar, 3 ms(-1) and 100% of power level. Finally, the optimized response was compared to the efficiency of a chemical cleaning with NaOH solution, with and without the use of ultrasound. By using NaOH, cleaning efficiency nearly triples, and it improves up to 25% by adding ultrasound. PMID- 24239100 TI - Comparative assessment of angiotensin II type 1 receptor blockers in the treatment of acute myocardial infarction: surmountable vs. insurmountable antagonist. AB - BACKGROUND: The mechanisms of antagonism vary between the angiotensin II type 1 receptor blockers (ARBs): insurmountable antagonism and surmountable antagonism. Recent retrospective observational studies suggest that ARBs may not have equivalent benefits in various clinical situations. The aim of this study was to compare the effect of two categories of ARBs on the long-term clinical outcomes of patients with acute myocardial infarction (AMI). METHODS: We analyzed the large-scale, prospective, observational Korea Acute Myocardial Infarction Registry study, which enrolled 2740 AMI patients. They divided by the prescription of surmountable ARBs or insurmountable ARBs at discharge. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, nonfatal MI, and re-percutaneous coronary intervention, coronary artery bypass graft surgery. RESULTS: In the overall population, the MACEs rate in 1 year was significantly higher in the surmountable ARB group (14.3% vs. 11.2%, p=0.025), which was mainly due to increased cardiac death (3.3% vs. 1.9%, p=0.031). Matching by propensity-score showed consistent results (MACEs rate: 14.9% vs. 11.4%, p=0.037). In subgroup analysis, the insurmountable ARB treatment significantly reduced the incidence of MACEs in patients with left ventricular ejection fraction greater than 40%, with a low killip class, with ST segment elevation MI, and with normal renal function. CONCLUSIONS: In our study, insurmountable ARBs were more effective on long-term clinical outcomes than surmountable ARBs in patients with AMI. PMID- 24239102 TI - Fatal combined immunodeficiency associated with heterozygous mutation in STAT1. AB - BACKGROUND: Mutations in the gene for the signal transducer and activator of transcription 1, STAT1, have been shown to be associated with death at an early age due to overwhelming viral infection (complete STAT1 deficiency) or, more commonly, selective deficiencies to mycobacterial or fungal infection (typically heterozygous STAT1 mutations). OBJECTIVES: To define the molecular basis of progressive combined immunodeficiency in a group of patients with fatal infections. METHODS: We studied a group of unrelated patients who displayed an unusual progressive form of combined immunodeficiency. Whole exome sequencing assisted in confirming a common genetic defect in this group, which consisted of a heterozygous mutation of the STAT1 gene. STAT1 protein level as well as function was assessed, and a detailed evaluation of the immune system, including analysis of thymus tissue, was performed. RESULTS: Patients were found to carry de novo heterozygous mutations in STAT1 encoding T385A, I294T, or C284R amino acid substitutions. STAT1 expression appeared significantly decreased as a result of these changes but not completely absent, with diminished signaling responses. This group display progressive loss in lymphocyte number and function accompanied by increasing autoimmune features as well as severe, fatal infections. CONCLUSIONS: These findings show that some heterozygous aberrations of STAT1 can be associated with progressive combined immunodeficiency, quite distinct from the limited susceptibilities to infection previously reported for heterozygous STAT1 mutations. These mutations were not inherited, rather, arose de novo in each case. Accompanied by significant patient mortality, this finding suggests that this class of STAT1 mutation is ultimately fatal due to overwhelming infection. PMID- 24239103 TI - Infections of intravascular bare metal stents: a case report and review of literature. AB - OBJECTIVE: The objective of the paper is to present a case of an infected bare metal stent in the left common iliac artery that was removed by an urgent operation, and to review the literature on diagnosis and outcome of infected coronary and non-coronary metal stents. METHODS: A systematic search of the Medline database was performed with the purpose of identifying risk factors, signs and symptoms, imaging strategies, and treatment modalities of bare metal stent infections, both coronary and peripheral. RESULTS: In total, 76 additional studies/case reports (48 non-coronary; 29 coronary) were included and analyzed. Intravascular bare metal stent infections are a rare but serious complication, often leading to emergency surgery (overall: 75.3%; non-coronary cases: 83.3%; coronary cases: 62.1%). In 25.0% of the non-coronary cases, infection led to amputation of an extremity or removal of viscera. Reported mortality was up to 32.5% of the cases (non-coronary: 22.9%; coronary 48.3%). Physicians should always be suspicious of a stent infection when patients present with aspecific symptoms such as fever and chills after stent placement. Additional imaging can be used to detect the presence of a pseudoaneurysm. A PET-CT is an ideal medium for identification of a stent infection. CONCLUSIONS: Intravascular stent infection is associated with a high risk of morbidity and mortality. Surgery is the preferred treatment option, but not always possible, especially in patients with a coronary stent. In selected cases, bare metal stent infections may be prevented by the use of prophylactic antibiotics at stent placement. PMID- 24239104 TI - Carotid endarterectomy with stent removal in management of in-stent restenosis: a safe, feasible, and effective technique. AB - INTRODUCTION: The optimal treatment of in-stent restenosis (ISR) is not determined. We describe the efficacy of carotid endarterectomy (CEA) with stent removal in the management of symptomatic ISR. METHODS: A 72-year-old man presented with recurrent right limb weakness 8 months after carotid artery stenting. Digital substraction angiography showed severe ISR (almost 99%). CEA with stent removal was performed. RESULTS: A total of 41 cases was reviewed: periarterial inflammation was shown in 10.3% of patients; 92.9% had clear intima media plane; and 85.4% had a good outcome. All patients remained stable at follow up. DISCUSSION: CEA with stent removal appears to be a safe, feasible, effective, and durable therapeutic option. PMID- 24239106 TI - How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease? AB - BACKGROUND AIMS: The protocols for differentiation of hepatocyte-like cells (HLCs) from mesenchymal stromal cells (MSCs) have been well established. Previous data have shown that MSCs and their derived HLCs were able to engraft injured liver and alleviate injuries induced by carbon tetrachloride. The goal of the current study was to determine the differences of MSCs and their derived HLCs in terms of therapeutic functions in liver diseases. METHODS: After hepatic differentiation of umbilical cord-derived MSCs in vitro, we detected both MSC and HLC expressions of adhesion molecules and chemokine receptor CXCR4 by flow cytometry; immunosuppressive potential and hepatocyte growth factor expression were determined by means of enzyme-linked immunosorbent assay. We compared the therapeutic effect for fulminant hepatic failure in a mouse model. RESULTS: MSC derived-HLCs expressed lower levels of hepatocyte growth factor, accompanied by impaired immunosuppression in comparison with MSCs. Furthermore, undifferentiated MSCs showed rescuing potentials superior to those in HLCs for the treatment of fulminant hepatic failure. CONCLUSIONS: After differentiation, HLCs lost several major properties in comparison with undifferentiated MSCs, which are beneficial for their application in liver diseases. Undifferentiated MSCs may be more appropriate than are HLCs for the treatment of liver diseases. PMID- 24239107 TI - Current concept for the use of PRP in arthroscopic surgery. AB - PRP is commonly used in sports medicine and because it is supposed to increase healing capacities of damaged tissues, it is expected to be increase efficiency or god clinical outcomes when added to arthroscopic surgical procedure. The current review of literature explores the evidence-based medicine supporting the use of PRP in three arthroscopic related disorders. Regarding cartilage lesions of the knee, many studies are exploring several aspect of cartilage lesion treatment. It appears that PRP, in some protocols with specific concentration, should be more efficient than current therapies in the treatment of early stages of knee OA, but only in the field of rheumatology or sport medicine, not when used during surgery. PRP have been used in ACL reconstruction, no benefit has been reported in any study regarding clinical or radiological outcomes. In shoulder cuff disorder, to date, no clinical benefit nor increased healing rate have been clearly reported. Thus, in 2013, it is clear that there is no evidence base medicine data supporting the use of PRP in arthroscopic surgery. PMID- 24239108 TI - Magnetically engineered Cd-free quantum dots as dual-modality probes for fluorescence/magnetic resonance imaging of tumors. AB - Magnetically engineered Cd-free CuInS2@ZnS:Mn quantum dots (QDs) were designed, synthesized, and evaluated as potential dual-modality probes for fluorescence and magnetic resonance imaging (MRI) of tumors in vivo. The synthesis of Mn-doped core-shell structured CuInS2@ZnS mainly comprised three steps, i.e., the preparation of fluorescent CuInS2 seeds, the particle surface coating of ZnS, and the Mn-doping of the ZnS shells. Systematic spectroscopy studies were carried out to illustrate the impacts of ZnS coating and the following Mn-doping on the optical properties of the QDs. In combination with conventional fluorescence, fluorescence excitation, and time-resolved fluorescence measurements, the structure of CuInS2@ZnS:Mn QDs prepared under optimized conditions presented a Zn gradient CuInS2 core and a ZnS outer shell, while Mn ions were mainly located in the ZnS shell, which well balanced the optical and magnetic properties of the resultant QDs. For the following in vivo imaging experiments, the hydrophobic CuInS2@ZnS:Mn QDs were transferred into water upon ligand exchange reactions by replacing the 1-dodecanethiol ligand with dihydrolipoic acid-poly(ethylene glycol) (DHLA-PEG) ligand. The MTT assays based on HeLa cells were carried out to evaluate the cytotoxicity of the current Cd-free CuInS2@ZnS:Mn QDs for comparing with that of water soluble CdTe QDs. Further in vivo fluorescence and MR imaging experiments suggested that the PEGylated CuInS2@ZnS:Mn QDs could well target both subcutaneous and intraperitoneal tumors in vivo. PMID- 24239109 TI - Simultaneous delivery of doxorubicin and curcumin encapsulated in liposomes of pegylated RGDK-lipopeptide to tumor vasculature. AB - Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2-3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy. PMID- 24239105 TI - Engineered T cells for cancer treatment. AB - Adoptively transferred T cells have the capacity to traffic to distant tumor sites, infiltrate fibrotic tissue and kill antigen-expressing tumor cells. Various groups have investigated different genetic engineering strategies designed to enhance tumor specificity, increase T cell potency, improve proliferation, persistence or migratory capacity and increase safety. This review focuses on recent developments in T cell engineering, discusses the clinical application of these engineered cell products and outlines future prospects for this therapeutic modality. PMID- 24239110 TI - Reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles for doxorubicin delivery. AB - We report a reducible copolymer self-assembled with superparamagnetic iron oxide nanoparticles (SPIONs) to deliver doxorubicin (DOX) for cancer therapy. The copolymer of reducible polyamidoamine (rPAA) with poly(ethylene glycol)(PEG)/dodecyl amine graft was synthesized by Michael addition. rPAA@SPIONs were formed by the alkyl grafts of reducible copolymers intercalated with the oleic acid layer capped on the surface of magnetite nanocrystals. The intercalating area formed a reservoir for hydrophobic anti-cancer drug (DOX), whilst the PEG moiety in the copolymers helped the nanoparticle well-dispersible in aqueous solution. We employed two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman (CARS) to investigate drug delivery in intra-cellular structures of live cells, and used Vivaview((r)) technique to show real-time inhibition efficacy of nanoparticles in live cells. rPAA@SPIONs present efficiently drug loading with reducible responsibility in vitro tests. Finally, rPAA@SPIONs were tested in mice with xenograft MDA-MB-231 breast tumor though i.v. injection and inhibited tumor growth efficiently. MRI was used to monitor nanoparticles aggregation in tumor site. Histology and Prussian blue on kidney, liver, and heart in mice indicated that DOX/rPAA@SPIONs showed no significant toxicity for mice organs after 24 days treatment. PMID- 24239111 TI - Induction of epithelial-to-mesenchymal transition in proximal tubular epithelial cells on microfluidic devices. AB - In proteinuric nephropathy, epithelial-to-mesenchymal transition (EMT) is an important mechanism that causes renal interstitial fibrosis. The precise role of EMT in the pathogenesis of fibrosis remains controversial, partly due to the absence of suitable in vitro or in vivo models. We developed two microfluidic and compartmental chips that reproduced the fluidic and three-dimensional microenvironment of proximal tubular epithelial cells in vivo. Using one microfluidic device, we stimulated epithelial cells with a flow of healthy human serum, heat-inactivated serum and complement C3a, which mimicked the flow of urine within the proximal tubule. We observed that epithelial cells exposed to serum proteins became apoptotic or developed a mesenchymal phenotype. Incubating cells with C3a induced similar features. However, cells exposed to heat inactivated serum did not adopt the mesenchymal phenotype. Furthermore, we successfully recorded the cellular morphological changes and the process of transmigration into basement membrane extract during EMT in real-time using another three-dimensional microdevice. In conclusion, we have established a cell culture system that mimics the native microenvironment of the proximal tubule to a certain extent. Our data indicates that EMT did occur in epithelial cells that were exposed to serum proteins, and C3a plays an essential role in this pathological process. PMID- 24239112 TI - Lower atherosclerotic burden in familial abdominal aortic aneurysm. AB - OBJECTIVE: Despite the apparent familial tendency toward abdominal aortic aneurysm (AAA) formation, the genetic causes and underlying molecular mechanisms are still undefined. In this study, we investigated the association between familial AAA (fAAA) and atherosclerosis. METHODS: Data were collected from a prospective database including AAA patients between 2004 and 2012 in the Erasmus University Medical Center, Rotterdam, The Netherlands. Family history was obtained by written questionnaire (93.1% response rate). Patients were classified as fAAA when at least one affected first-degree relative with an aortic aneurysm was reported. Patients without an affected first-degree relative were classified as sporadic AAA (spAAA). A standardized ultrasound measurement of the common carotid intima-media thickness (CIMT), a marker for generalized atherosclerosis, was routinely performed and patients' clinical characteristics (demographics, aneurysm characteristics, cardiovascular comorbidities and risk factors, and medication use) were recorded. Multivariable linear regression analyses were used to assess the mean adjusted difference in CIMT and multivariable logistic regression analysis was used to calculate associations of increased CIMT and clinical characteristics between fAAA and spAAA. RESULTS: A total of 461 AAA patients (85% men, mean age, 70 years) were included in the study; 103 patients (22.3%) were classified as fAAA and 358 patients (77.7%) as spAAA. The mean (standard deviation) CIMT in patients with fAAA was 0.89 (0.24) mm and 1.00 (0.29) mm in patients with spAAA (P = .001). Adjustment for clinical characteristics showed a mean difference in CIMT of 0.09 mm (95% confidence interval, 0.02-0.15; P = .011) between both groups. Increased CIMT, smoking, hypertension, and diabetes mellitus were all less associated with fAAA compared with spAAA. CONCLUSIONS: The current study shows a lower atherosclerotic burden, as reflected by a lower CIMT, in patients with fAAA compared with patients with spAAA, independent of common atherosclerotic risk factors. These results support the hypothesis that although atherosclerosis is a common underlying feature in patients with aneurysms, atherosclerosis is not the primary driving factor in the development of fAAA. PMID- 24239113 TI - The use of cryopreserved aortoiliac allograft for aortic reconstruction in the United States. AB - BACKGROUND: Aortic infections, even with treatment, have a high mortality and risk of recurrent infection and limb loss. Cryopreserved aortoiliac allograft (CAA) has been proposed for aortic reconstruction to improve outcomes in this high-risk population. METHODS: A multicenter study using a standardized database was performed at 14 of the 20 highest volume institutions that used CAA for aortic reconstruction in the setting of infection or those at high risk for prosthetic graft infection. RESULTS: Two hundred twenty patients (mean age, 65; male:female, 1.6/1) were treated since 2002 for culture positive aortic graft infection (60%), culture negative aortic graft infection (16%), enteric fistula/erosion (15%), infected pseudoaneurysm adjacent to the aortic graft (4%), and other (4%). Intraop cultures indicated infection in 66%. Distal anastomosis was to the femoral artery and iliac. Mean hospital length of stay was 24 days, and 30-day mortality was 9%. Complications occurred in 24% and included persistent sepsis (n = 17), CAA thrombosis (n = 9), CAA rupture (n = 8), recurrent CAA/aortic infection (n = 8), CAA pseudoaneurysm (n = 6), recurrence of aortoenteric fistula (n = 4), and compartment syndrome (n = 1). Patients with full graft excision had significantly better outcomes. Ten (5%) patients required allograft explant. Mean follow-up was 30 +/- 3 months. Freedom from graft-related complications, graft explant, and limb loss was 80%, 88%, and 97%, respectively, at 5 years. Primary graft patency was 97% at 5 years, and patient survival was 75% at 1 year and 51% at 5 years. CONCLUSIONS: This largest study of CAA indicates that CAA allows aortic reconstruction in the setting of infection or those at high risk for infection with lower early and long-term morbidity and mortality than other previously reported treatment options. Repair with CAA is associated with low rates of aneurysm formation, recurrent infection, aortic blowout, and limb loss. We believe that CAA should be considered a first line treatment of aortic infections. PMID- 24239114 TI - Operative technique for tracheo-innominate artery fistula repair. AB - Tracheo-innominate artery fistula is fatal unless treated surgically. We describe our surgical approach and results in seven patients. The average patient age was 15.7 years; all patients had prior severe neurological deficits. Three of seven patients were in hemorrhagic shock; control of preoperative bleeding was achieved with tracheostomy tube cuff overinflation. The innominate artery and the trachea were exposed through a collar incision and partial upper sternotomy. The innominate artery was divided at the aortic arch and at the bifurcation, with one exception. Cerebral blood flow was monitored by the blood pressure difference in the bilateral upper extremities and by near-infrared spectroscopy. The tracheal fistula was left adherent to the innominate artery in all but one patient. All patients were discharged without new neurologic deficits or severe morbidity. Overall survival was 84% at 37 months, without any vascular, tracheal, or neurological events. PMID- 24239115 TI - Reinfection after resection and revascularization of infected infrarenal abdominal aortic grafts. AB - OBJECTIVE: Despite advances in perioperative care, long-term and amputation-free survival rates are poor after resection of infected abdominal aortic grafts. We reviewed our cases to determine the rate of reinfection and risk factors for mortality and limb loss. METHODS: We reviewed cases with infrarenal aortic graft infection from 1999 to 2013. Cases requiring graft excision were included for analysis. Thoracic and thoracoabdominal aortic grafts were excluded. Reconstruction types included both extra-anatomic and in situ grafts. Patient comorbidities, surgical outcomes, and known reinfection rates were assessed. Univariate and Kaplan-Meier analysis were performed. RESULTS: Twenty-eight patients had resection of infected infrarenal abdominal aortic grafts during the study period. Most patients (26/28; 93%) had infected aortoiliac or aortofemoral prosthetic bypass grafts, but two of 28 patients had infected endovascular aortoiliac stent grafts. The median age was 69 years (range, 46-86 years), with 68% men and 32% women. Aortoenteric fistulae or graft-enteric erosions were noted in 12 of 28 (43%) patients at operation. There were 79% of patients who had in situ reconstruction, including 4 (14%) with polyester, 1 (4%) with polytetrafluoroethylene, 3 (11%) with cadaveric homograft, 3 (11%) with composite grafts, and 11 (39%) with native femoropopliteal vein grafts. Five (18%) patients had extra-anatomic bypass and one had excision without revascularization. In hospital mortality after initial graft excision and revascularization occurred in two (7%) patients. Seven (25%) patients had evidence of reinfection after a median of 20 months, of whom five underwent reintervention with two additional in hospital deaths. All in-hospital deaths occurred in patients with graft-enteric contamination. Overall limb salvage and survival at a mean follow-up of 2.5 years were 82% and 46%, respectively, and did not differ among revascularization types (P = .85 and .74). One-year amputation-free survival was 47% overall. Three patients with native femoropopliteal vein graft repair required amputation in follow-up. Diabetes was the only observed risk factor for amputation (P = .05). Risks for mortality included history of cerebrovascular disease (P = .05) and shock on presentation (P = .04). No other comorbid condition, type of revascularization, or perioperative complication was associated with limb loss or mortality on univariate analysis. CONCLUSIONS: Revascularization after excision of infected abdominal aortic grafts can be done with acceptable in-hospital morbidity and mortality. Reinfection is problematic, regardless of revascularization conduit, and is associated with limb loss and death. New and aggressive local anti-infective strategies are warranted. PMID- 24239116 TI - Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis. AB - OBJECTIVE: Optimal platelet inhibition is an important therapeutic adjunct in patients with carotid artery stenosis undergoing carotid artery stenting (CAS). Clopidogrel resistance is associated with increased periprocedural thromboembolic complications from neurovascular stent placement procedures. The addition of cilostazol to dual antiplatelet therapy (DAT) has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention. This study was undertaken to evaluate the impact of adjunctive cilostazol in patients with CAS. METHODS: Platelet function was assessed by light transmittance aggregometry using the VerifyNow assay. Sixty-four consecutive patients who underwent CAS received standard DAT, clopidogrel (75 mg daily), and aspirin (100 mg daily) more than 4 weeks before the procedure. From 2010 to 2011 (period I), 28 patients underwent CAS under standard DAT. From 2011 to 2013 (period II), 36 patients prospectively had preoperative assessment of platelet function, and 13 patients with clopidogrel resistance received adjunctive cilostazol (200 mg daily) in addition to standard DAT. The incidence of new ipsilateral ischemic lesions on diffusion-weighted imaging a day after CAS and ischemic or hemorrhagic events within 30 days was assessed. RESULTS: Clopidogrel resistance was indentified in 12 patients (43%) in period I and 13 patients (36%) in period II (P = .615). In period II, the addition of cilostazol significantly decreased P2Y12 reaction units and % inhibition (P = .006 and P = .005, respectively), and there was a significant difference in P2Y12 reaction units between the two periods. New ipsilateral ischemic lesions were significantly decreased in period II (2/36 patients) compared with period I (7/28 patients; P = .034); however, there was no significant difference in hemorrhagic and thromboembolic events between the two periods. CONCLUSIONS: Adjunctive cilostazol (triple antiplatelet therapy) in clopidogrel-resistant patients reduces the rate of clopidogrel resistance and suppresses new ischemic lesions without hemorrhagic complications, as compared with standard DAT. Antiplatelet management based on the evaluation of antiplatelet resistance would be required for prevention of perioperative thromboembolic complications in CAS. PMID- 24239117 TI - Meiotic double-strand breaks uncover and protect against mitotic errors in the C. elegans germline. AB - In sexually reproducing multicellular organisms, genetic information is propagated via the germline, the specialized tissue that generates haploid gametes. The C. elegans germline generates gametes in an assembly line-like process-mitotic divisions under the control of the stem cell niche produce nuclei that, upon leaving the niche, enter into meiosis and progress through meiotic prophase [1]. Here, we characterize the effects of perturbing cell division in the mitotic region of the C. elegans germline. We show that mitotic errors result in a spindle checkpoint-dependent cell-cycle delay, but defective nuclei are eventually formed and enter meiosis. These defective nuclei are eliminated by programmed cell death during meiotic prophase. The cell death-based removal of defective nuclei does not require the spindle checkpoint but instead depends on the DNA damage checkpoint. Removal of nuclei resulting from errors in mitosis also requires Spo11, the enzyme that creates double-strand breaks to initiate meiotic recombination. Consistent with this, double-strand breaks are increased in number and persist longer in germlines with mitotic defects. These findings reveal that the process of initiating meiotic recombination inherently selects against nuclei with abnormal chromosomal content generated by mitotic errors, thereby ensuring the genomic integrity of gametes. PMID- 24239118 TI - Activation of GABAergic neurons in the interpeduncular nucleus triggers physical nicotine withdrawal symptoms. AB - BACKGROUND: Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes. RESULTS: Here we show that induction of physical nicotine withdrawal symptoms activates GABAergic neurons within the interpeduncular nucleus (IPN). Optical activation of IPN GABAergic neurons via light stimulation of channelrhodopsin elicited physical withdrawal symptoms in both nicotine-naive and chronic-nicotine-exposed mice. Dampening excitability of GABAergic neurons during nicotine withdrawal through IPN-selective infusion of an NMDA receptor antagonist or through blockade of IPN neurotransmission from the medial habenula reduced IPN neuronal activation and alleviated withdrawal symptoms. During chronic nicotine exposure, nicotinic acetylcholine receptors containing the beta4 subunit were upregulated in somatostatin interneurons clustered in the dorsal region of the IPN. Blockade of these receptors induced withdrawal signs more dramatically in nicotine-dependent compared to nicotine-naive mice and activated nonsomatostatin neurons in the IPN. CONCLUSIONS: Together, our data indicate that therapeutic strategies to reduce IPN GABAergic neuron excitability during nicotine withdrawal, for example, by activating nicotinic receptors on somatostatin interneurons, may be beneficial for alleviating withdrawal symptoms and facilitating smoking cessation. PMID- 24239119 TI - The GTPase-activating protein RN-tre controls focal adhesion turnover and cell migration. AB - BACKGROUND: Integrin-mediated adhesion of cells to the extracellular matrix (ECM) relies on the dynamic formation of focal adhesions (FAs), which are biochemical and mechanosensitive platforms composed of a large variety of cytosolic and transmembrane proteins. During migration, there is a constant turnover of ECM contacts that initially form as nascent adhesions at the leading edge, mature into FAs as actomyosin tension builds up, and are then disassembled at the cell rear, thus allowing for cell detachment. Although the mechanisms of FA assembly have largely been defined, the molecular circuitry that regulates their disassembly still remains elusive. RESULTS: Here, we show that RN-tre, a GTPase activating protein (GAP) for Rabs including Rab5 and Rab43, is a novel regulator of FA dynamics and cell migration. RN-tre localizes to FAs and to a pool of Rab5 positive vesicles mainly associated with FAs undergoing rapid remodeling. We found that RN-tre inhibits endocytosis of beta1, but not beta3, integrins and delays the turnover of FAs, ultimately impairing beta1-dependent, but not beta3 dependent, chemotactic cell migration. All of these effects are mediated by its GAP activity and rely on Rab5. CONCLUSIONS: Our findings identify RN-tre as the Rab5-GAP that spatiotemporally controls FA remodeling during chemotactic cell migration. PMID- 24239120 TI - Antagonistic spindle motors and MAPs regulate metaphase spindle length and chromosome segregation. AB - Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at characteristic constant length [1-3]. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules (MTs) and their interactions with motors and MT-associated proteins (MAPs). Spindle length is further proposed to be important for chromosome segregation fidelity, as cells with shorter- or longer-than-normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force-balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature control with live-cell imaging to monitor the effect of deleting or switching off different combinations of antagonistic force contributors in the fission yeast metaphase spindle. We show that the spindle midzone proteins kinesin-5 cut7p and MT bundler ase1p contribute to outward pushing forces and that the spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward-pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and in some combinations also partially rescued chromosome segregation defects. PMID- 24239121 TI - Low-intensity focused ultrasound modulates monkey visuomotor behavior. AB - In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution. PMID- 24239122 TI - An octopamine-mushroom body circuit modulates the formation of anesthesia resistant memory in Drosophila. AB - BACKGROUND: Drosophila olfactory aversive conditioning produces two components of intermediate-term memory: anesthesia-sensitive memory (ASM) and anesthesia resistant memory (ARM). Recently, the anterior paired lateral (APL) neuron innervating the whole mushroom body (MB) has been shown to modulate ASM via gap junctional communication in olfactory conditioning. Octopamine (OA), an invertebrate analog of norepinephrine, is involved in appetitive conditioning, but its role in aversive memory remains uncertain. RESULTS: Here, we show that chemical neurotransmission from the APL neuron, after conditioning but before testing, is necessary for aversive ARM formation. The APL neurons are tyramine, Tbetah, and OA immunopositive. An adult-stage-specific RNAi knockdown of Tbetah in the APL neurons or Octbeta2R OA receptors in the MB alpha'beta' Kenyon cells (KCs) impaired ARM. Importantly, an additive ARM deficit occurred when Tbetah knockdown in the APL neurons was in the radish mutant flies or in the wild-type flies with inhibited serotonin synthesis. CONCLUSIONS: OA released from the APL neurons acts on alpha'beta' KCs via Octbeta2R receptor to modulate Drosophila ARM formation. Additive effects suggest that two parallel ARM pathways, serotoninergic DPM-alphabeta KCs and octopaminergic APL-alpha'beta' KCs, exist in the MB. PMID- 24239123 TI - Cingulate-hippocampus coherence and trajectory coding in a sequential choice task. AB - Interactions between cortex and hippocampus are believed to play a role in the acquisition and maintenance of memories. Distinct types of coordinated oscillatory activity, namely at theta frequency, are hypothesized to regulate information processing in these structures. We investigated how information processing in cingulate cortex and hippocampus relates to cingulate-hippocampus coordination in a behavioral task in which rats choose from four possible trajectories according to a sequence. We found that the accuracy with which cingulate and hippocampal populations encode individual trajectories changes with the pattern of cingulate-hippocampal theta coherence over the course of a trial. Initial theta coherence at ~8 Hz during trial onsets lowers by ~1 Hz as animals enter decision stages. At these stages, hippocampus precedes cingulate in processing increased amounts of task-relevant information. We hypothesize that lower theta frequency coordinates the integration of hippocampal contextual information by cingulate neuronal populations, to inform choices in a task-phase dependent manner. PMID- 24239124 TI - Parvalbumin-expressing interneurons linearly control olfactory bulb output. AB - In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding. Using paired recordings, we find that PV cells form reciprocal connections with the majority of nearby mitral cells, in contrast to the sparse connectivity between mitral and granule cells. In vivo calcium imaging in awake mice reveals that PV cells are broadly tuned to odors. Furthermore, selective PV cell inactivation enhances mitral cell responses in a linear fashion while maintaining mitral cell odor preferences. Thus, dense connections between mitral and PV cells underlie an inhibitory circuit poised to modulate the gain of olfactory bulb output. PMID- 24239125 TI - Dissecting local circuits: parvalbumin interneurons underlie broad feedback control of olfactory bulb output. AB - In the mouse olfactory bulb, information from sensory neurons is extensively processed by local interneurons before being transmitted to the olfactory cortex by mitral and tufted (M/T) cells. The precise function of these local networks remains elusive because of the vast heterogeneity of interneurons, their diverse physiological properties, and their complex synaptic connectivity. Here we identified the parvalbumin interneurons (PVNs) as a prominent component of the M/T presynaptic landscape by using an improved rabies-based transsynaptic tracing method for local circuits. In vivo two-photon-targeted patch recording revealed that PVNs have exceptionally broad olfactory receptive fields and exhibit largely excitatory and persistent odor responses. Transsynaptic tracing indicated that PVNs receive direct input from widely distributed M/T cells. Both the anatomical and functional extent of this M/T->PVN->M/T circuit contrasts with the narrowly confined M/T->granule cell->M/T circuit, suggesting that olfactory information is processed by multiple local circuits operating at distinct spatial scales. PMID- 24239127 TI - Power analysis to detect time trends on population-based cancer registries data: When size really matters. AB - Detecting statistically significant trends in incidence with cancer registries data not only depends on the size of their covered population but also on the levels of incidence rates, duration of diagnostic period and type of temporal variation. We simulated sample sizes of newly diagnosed cases based on a variety of plausible levels of cancer rates and scenarios of changing trends over a period of about 30 years. Each simulated set of cases was then analysed with joinpoint regression models. The power was derived as the relative frequency of the simulation runs where the p-value of the coefficient was less than 0.05 under the alternative model. In case of a decreasing trend with no change of direction (join), an Annual Percentage Change (APC) of 1% for an average rate of 10 per 100,000 is detectable in populations of half a million inhabitants or more with a nominal power of 80%. In a model with one joinpoint followed by an increasing trend, the minimum detectable APC increases, and an APC of about 2%, can be detected only with populations of at least 2 million. For analyses requiring a larger sample size than the actual covered population, alternative organisational strategies should be considered, such as an extension of population coverage or data pooling and merging from registries with comparable data. (i.e. when heterogeneity across merging registries is low or acceptable for the specific study question). PMID- 24239126 TI - Diverse spatial reference frames of vestibular signals in parietal cortex. AB - Reference frames are important for understanding how sensory cues from different modalities are coordinated to guide behavior, and the parietal cortex is critical to these functions. We compare reference frames of vestibular self-motion signals in the ventral intraparietal area (VIP), parietoinsular vestibular cortex (PIVC), and dorsal medial superior temporal area (MSTd). Vestibular heading tuning in VIP is invariant to changes in both eye and head positions, indicating a body (or world)-centered reference frame. Vestibular signals in PIVC have reference frames that are intermediate between head and body centered. In contrast, MSTd neurons show reference frames between head and eye centered but not body centered. Eye and head position gain fields were strongest in MSTd and weakest in PIVC. Our findings reveal distinct spatial reference frames for representing vestibular signals and pose new challenges for understanding the respective roles of these areas in potentially diverse vestibular functions. PMID- 24239128 TI - The murky middle ground - when ethnographers engage public health. AB - This commentary revisits dilemmas of relevance that applied anthropology in the U.S. has long grappled with, no matter the rigor and depth of inquiry. Direct action, collaborative research and active public engagement offer proven alternatives for upping the participatory quotient, but they remain the exception. A third, more common, middle ground may be also discerned, sometimes involving the sort of "dirty work" that seems to lie outside of one's professional remit. Commitment to such work, it turns out, is not simply a matter of character or disciplinary ethics, but of the terms and conditions of anthropological employment. Even without the "second shift" of going public with one's findings, critically positioned research can keep problematic issues that might otherwise slip into the convenient silences of social and economic policy. PMID- 24239130 TI - Dysfunctional glutamatergic and gamma-aminobutyric acidergic activities in prefrontal cortex of mice in social defeat model of depression. AB - BACKGROUND: Depression is a complex neuropsychiatric syndrome that is often very severe and life threatening. In spite of the remarkable progress in understanding the neural biology, the etiopathophysiology of depression is still elusive. In this study, we have investigated molecular mechanisms in the prefrontal cortex of mice showing depression-like phenotype induced by chronic defeat stress. METHODS: Depression-like phenotype was induced in C57BL/6 mice by subjecting them to a 10 day social defeat paradigm. The metabolic activity of excitatory (glutamatergic) and inhibitory (gamma-aminobutyric acid [GABA]ergic) neurons of the prefrontal cortex was measured by (1)H-[(13)C]-nuclear magnetic resonance spectroscopy together with infusion of [1,6-(13)C2]glucose. In addition, the expression level of genes associated with glutamatergic and GABAergic pathways was monitored by quantitative polymerase chain reaction. RESULTS: Mice showing depression-like phenotype exhibit significant reduction in the levels of glutamate, glutamine, N acetyl aspartate, and taurine in the prefrontal cortex. Most importantly, findings of reduced (13)C labeling of glutamate-C4, glutamate-C3, and GABA-C2 from [1,6-(13)C2]glucose indicate decreased glutamatergic and GABAergic neuronal metabolism and neurotransmitter cycling in the depressed mice. The reduced glutamine-C4 labeling suggests decreased neurotransmitter cycling in depression. Quantitative polymerase chain reaction analysis revealed reduced transcripts of Gad1 and Eaat2 genes, which code for enzymes involved in the synthesis of GABA and the clearance of glutamate from synapses, respectively. CONCLUSIONS: These data indicate that the activities of glutamatergic and GABAergic neurons are reduced in mice showing a depression-like phenotype, which is supported by molecular data for the expression of genes involved in glutamate and GABA pathways. PMID- 24239129 TI - Methamphetamine downregulates striatal glutamate receptors via diverse epigenetic mechanisms. AB - BACKGROUND: Chronic methamphetamine (METH) exposure causes neuroadaptations at glutamatergic synapses. METHODS: To identify the METH-induced epigenetic underpinnings of these neuroadaptations, we injected increasing METH doses to rats for 2 weeks and measured striatal glutamate receptor expression. We then quantified the effects of METH exposure on histone acetylation. We also measured METH-induced changes in DNA methylation and DNA hydroxymethylation. RESULTS: Chronic METH decreased transcript and protein expression of GluA1 and GluA2 alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and GluN1 N methyl-D-aspartate receptor subunits. These changes were associated with altered electrophysiological glutamatergic responses in striatal neurons. Chromatin immunoprecipitation-polymerase chain reaction revealed that METH decreased enrichment of acetylated histone H4 on GluA1, GluA2, and GluN1 promoters. Methamphetamine exposure also increased repressor element-1 silencing transcription factor (REST) corepressor 1, methylated CpG binding protein 2, and histone deacetylase 2 enrichment, but not of sirtuin 1 or sirtuin 2, onto GluA1 and GluA2 gene sequences. Moreover, METH caused interactions of REST corepressor 1 and methylated CpG binding protein 2 with histone deacetylase 2 and of REST with histone deacetylase 1. Surprisingly, methylated DNA immunoprecipitation and hydroxymethylated DNA immunoprecipitation-polymerase chain reaction revealed METH induced decreased enrichment of 5-methylcytosine and 5-hydroxymethylcytosine at GluA1 and GluA2 promoter sequences. Importantly, the histone deacetylase inhibitor, valproic acid, blocked METH-induced decreased expression of AMPAR and N-methyl-D-aspartate receptor subunits. Finally, valproic acid also attenuated METH-induced decrease H4K16Ac recruitment on AMPAR gene sequences. CONCLUSIONS: These observations suggest that histone H4 hypoacetylation may be the main determinant of METH-induced decreased striatal glutamate receptor expression. PMID- 24239131 TI - Neural correlates of impaired cognitive control over working memory in schizophrenia. AB - BACKGROUND: One of the most common deficits in patients with schizophrenia (SZ) is in working memory (WM), which has wide-reaching impacts across cognition. However, previous approaches to studying WM in SZ have used tasks that require multiple cognitive-control processes, making it difficult to determine which specific cognitive and neural processes underlie the WM impairment. METHODS: We used functional magnetic resonance imaging to investigate component processes of WM in SZ. Eighteen healthy controls (HCs) and 18 patients with SZ performed an item-recognition task that permitted separate neural assessments of 1) WM maintenance, 2) inhibition, and 3) interference control in response to recognition probes. RESULTS: Before inhibitory demands, posterior ventrolateral prefrontal cortex (VLPFC), an area involved in WM maintenance, was activated to a similar degree in both HCs and patients, indicating preserved maintenance operations in SZ. When cued to inhibit items from WM, HCs showed reduced activation in posterior VLPFC, commensurate with appropriately inhibiting items from WM. However, these inhibition-related reductions were absent in patients. When later probed with items that should have been inhibited, patients showed reduced behavioral performance and increased activation in mid-VLPFC, an area implicated in interference control. A mediation analysis indicated that impaired inhibition led to increased reliance on interference control and reduced behavioral performance. CONCLUSIONS: In SZ, impaired control over memory, manifested through proactive inhibitory deficits, leads to increased reliance on reactive interference-control processes. The strain on interference-control processes results in reduced behavioral performance. Thus, inhibitory deficits in SZ may underlie widespread impairments in WM and cognition. PMID- 24239132 TI - Lung transplantation in children. Specific aspects. AB - Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. PMID- 24239134 TI - [Cell therapy in inborn errors of metabolism]. PMID- 24239133 TI - Best approach for posterior mediastinal goiter removal: transcervical incision and lateral thoracotomy. AB - Surgical removal of intrathoracic goiter can be performed by a cervical approach in the majority of patients. Review of literature shows that experienced surgeons need to perform an extracervical approach in 2-3% of cases. In spite of surgical management of substernal goiter is well defined, there is little available information about surgical approach of intrathoracic goiters extending beyond the aortic arch into the posterior mediastinum. We report two cases and propose combination of cervical incision and muscle-sparing lateral thoracotomy for posterior mediastinal goiter removal. In such cases, we do not favour sternotomy as posterior mediastinum is inaccessible due to the presence of heart and great vessels anterior to the thyroidal mass that would lead to perform a perilous blind dissection. Based in our experience, transcervical and thoracotomy approach is indicated for a complete and safe posterior mediastinal goiter removal. PMID- 24239135 TI - [Harlequin ichthyosis]. PMID- 24239136 TI - Accelerated radial Fourier-velocity encoding using compressed sensing. AB - PURPOSE: Phase Contrast Magnetic Resonance Imaging (MRI) is a tool for non invasive determination of flow velocities inside blood vessels. Because Phase Contrast MRI only measures a single mean velocity per voxel, it is only applicable to vessels significantly larger than the voxel size. In contrast, Fourier Velocity Encoding measures the entire velocity distribution inside a voxel, but requires a much longer acquisition time. For accurate diagnosis of stenosis in vessels on the scale of spatial resolution, it is important to know the velocity distribution of a voxel. Our aim was to determine velocity distributions with accelerated Fourier Velocity Encoding in an acquisition time required for a conventional Phase Contrast image. MATERIALS AND METHODS: We imaged the femoral artery of healthy volunteers with ECG-triggered, radial CINE acquisition. Data acquisition was accelerated by undersampling, while missing data were reconstructed by Compressed Sensing. Velocity spectra of the vessel were evaluated by high resolution Phase Contrast images and compared to spectra from fully sampled and undersampled Fourier Velocity Encoding. By means of undersampling, it was possible to reduce the scan time for Fourier Velocity Encoding to the duration required for a conventional Phase Contrast image. RESULTS: Acquisition time for a fully sampled data set with 12 different Velocity Encodings was 40 min. By applying a 12.6-fold retrospective undersampling, a data set was generated equal to 3:10 min acquisition time, which is similar to a conventional Phase Contrast measurement. Velocity spectra from fully sampled and undersampled Fourier Velocity Encoded images are in good agreement and show the same maximum velocities as compared to velocity maps from Phase Contrast measurements. CONCLUSION: Compressed Sensing proved to reliably reconstruct Fourier Velocity Encoded data. Our results indicate that Fourier Velocity Encoding allows an accurate determination of the velocity distribution in vessels in the order of the voxel size. Thus, compared to normal Phase Contrast measurements delivering only mean velocities, no additional scan time is necessary to retrieve meaningful velocity spectra in small vessels. PMID- 24239137 TI - The follow-up surgical results of coarctation of the aorta procedures in a cohort of Chinese children from a single institution. AB - OBJECTIVES: The aim of this study was to evaluate the results following surgeries for the treatment of coarctation of the aorta in Chinese paediatric patients and to compare the surgery outcomes between simple and complex coarctation procedures. METHODS: Between January 2006 and December 2011, 107 consecutive paediatric patients with coarctation of the aorta underwent surgery. Forty-four patients (41.12%) were classified as having simple coarctations (group A), and 54 patients (50.47%) were classified as having complex coarctations (group B). Echocardiography and the resting systolic blood pressure were evaluated prior to the operation, at one month following the operation, and then once annually. RESULTS: Follow-up was 93.5% complete (100 patients), without significant differences between the two groups. Arch hypoplasias and bicuspid aortic valves were initially present in 10 (9.35%) and 11 (10.28%) of 107 patients, respectively. There were no deaths among the group A patients and three (5.56%) early deaths among the group B patients. There was a significant difference in the restenosis incidence rate between the two groups during the most recent follow-up consultations (p<0.05). Additionally, only 10 of 43 group A and 10 of 51 group B patients had persistently abnormal blood pressures during the annual follow-up consultations. CONCLUSIONS: The postoperative restenosis ratio was increased in the complex coarctation group compared with the simple coarctation group. Additionally, the complex coarctation patients who did not have restenosis at follow-up had a lower proportion of hypertension. PMID- 24239138 TI - Diagnosis of feline acute intermittent porphyria presenting with erythrodontia requires molecular analyses. AB - Erythrodontia is the hallmark of human congenital erythropoietic porphyria (CEP), but is also a major phenotypic feature of acute intermittent porphyria (AIP) in cats. In this study, detailed biochemical and molecular analyses were performed on two unrelated cats with autosomal dominant AIP that presented with erythrodontia, yellow-brown urine and mild changes in erythrocytes. The cats had elevated concentrations of urinary 5-aminolevulinic acid and porphobilinogen, and half normal erythrocytic hydroxymethylbilane synthase (HMBS) activity. Two novel HMBS mutations were detected; one cat had a deletion (c.107_110delACAG) and one cat had a splicing alteration (c.826-1G>A), both leading to premature stop codons and truncated proteins (p.D36Vfs 6 and p.L276Efs 6, respectively). These studies highlight the importance of appropriate biochemical and molecular genetic analyses for the accurate diagnoses of porphyrias in cats and extend the molecular genetic heterogeneity of feline AIP. Thus, although erythrodontia is a classic sign of congenital erythropoietic porphyria in human beings, cats with erythrodontia may have acute intermittent porphyria, a hepatic porphyria. PMID- 24239139 TI - Dexmedetomidine is a very safe and useful drug for sedation during third molar extraction, easily reversed with verbal or physical stimuli. PMID- 24239140 TI - Dautrey's procedure: an alternative for the treatment of recurrent mandibular dislocation in patients with pneumatization of the articular eminence. AB - Temporomandibular joint (TMJ) dislocation is an involuntary forward movement of the mandible beyond the articular eminence with the condyle remaining stuck in the anterior-most position, leaving the patient unable to close their mouth. Conservative treatment for this condition includes the injection of sclerosing agents or the intramuscular administration of botulinum toxin type A, while surgical therapy requires either removal or augmentation of the articular eminence. Once the surgical treatment plan has been determined, pneumatization of the articular eminence may turn a relatively simple procedure into a great surgical challenge. We present herein the cases of two patients suffering from recurrent mandibular dislocation who happened to have pneumatization of the articular eminences. Both patients were treated with a down-fracture of the zygomatic arch, known as Dautrey's procedure, modified by the application of a miniplate connecting the displaced arch and the lateral portion of the articular eminence. Neither patient had suffered a new episode of dislocation at their most recent postsurgical visit. PMID- 24239141 TI - In vitro mechanical assessment of 2.0-mm system three-dimensional miniplates in anterior mandibular fractures. AB - This study constituted a comparative assessment of the mechanical resistance of square and rectangular 2.0-mm system three-dimensional miniplates as compared to the standard configuration using two straight miniplates. 90 polyurethane replica mandibles were used for the mechanical trials. Groups 1, 2, and 3 simulated complete symphyseal fractures characterized by linear separation of the central incisors; groups 4, 5, and 6 simulated parasymphyseal fractures with an oblique configuration. Groups 1 and 4 represented the standard method with two straight miniplates set parallel to one another. Square miniplates were used in groups 2 and 5, and rectangular miniplates in groups 3 and 6. A universal testing machine set to a velocity of 10mm/min and delivering a vertical linear load to the first left molar was used to test each group. Maximum load values and load values with pre-established dislocation of 5mm were obtained and submitted to statistical analysis using a calculated reliability interval of 95%. The mechanical performances of the devices were similar, except in the case of rectangular plates used in the parasymphyseal fractures. The innovative fixation methods used showed significantly better results in the case of symphyseal fractures. PMID- 24239142 TI - Longitudinal quantitative MRI in multiple system atrophy and progressive supranuclear palsy. AB - OBJECTIVE: MRI has been used in parkinsonism to assess atrophy, tissue water diffusivity, and mineral deposition but usually at a single time-point. However, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are progressive diseases. This study assessed the value of longitudinal MRI in characterizing the time course of the degenerative process. METHODS: Two serial MRIs (mean 23 months apart) were retrospectively analyzed in 12 MSA, 6 PSP, and 18 age and sex matched controls. Assessment included selected cross-sectional areas, regional apparent diffusion coefficient (ADC) and gradient echo (GRE) intensity ratios of the lateral ventricles, caudate, putamen, middle cerebellar peduncle, pons and midbrain. RESULTS: On follow-up imaging, there was a larger ADC increase in the putamen in PSP over time compared to controls (p = 0.02). In MSA there was greater volume loss in the pons over time compared to controls (p = 0.002). In MSA the changes in middle cerebellar peduncle ADC were correlated with motor symptom severity according to the Unified Parkinson's Disease Rating Scale Part III (p = 0.005). CONCLUSIONS: Evidence of progressive neurodegeneration can be observed on MRI in MSA and PSP within two years consisting of increasing putaminal ADC in PSP and pontine atrophy in MSA. PMID- 24239143 TI - Evaluation of patient-relevant outcomes of lymphedema and lipedema treatment: development and validation of a new benefit tool. AB - OBJECTIVES: Patient-relevant treatment benefit is traditionally measured with health-related quality of life (HRQoL) instruments. The Patient Benefit Index (PBI) methodology allows for a more direct measurement, with the patients rating both importance and achievement of treatment goals. Here, we developed and validated a PBI version specific for the assessment of benefit in lymphedema and lipedema treatment (PBI-L). METHODS: The development included five steps: (1) open item collection; (2) consensus of items in a multidisciplinary expert panel; (3) application of the German PBI-L in a cross-sectional study (n = 301); (4) translation into English; (5) application of the English PBI-L in a randomized clinical trial (n = 82). Subscales were developed using factor analysis. Construct validity was analyzed by correlating PBI-L and convergent criteria such as HRQoL and quality of care. To test for responsiveness, the association to change in HRQoL measures was computed. RESULTS: Floor and ceiling effects were low. There were few missing values. Two well-interpretable subscales were found with Cronbach's alpha >0.8 each. Global and subscale scores correlated with convergent criteria and with change in disease-specific HRQoL, but not with change in generic HRQoL. CONCLUSIONS: The PBI-L is an internally consistent, valid, and responsive instrument for the assessment of patient-relevant benefit of edema treatment. PMID- 24239144 TI - What is the best option for elective repair of an abdominal aortic aneurysm in a young fit patient? AB - OBJECTIVE: The lower procedural risk associated with endovascular aneurysm repair (EVAR) compared with open aneurysm repair (OAR) is well known. Younger patients are likely to represent a group at low perioperative risk. The long-term durability and late complications following EVAR may have more significance when considering the optimal treatment for young patients with a longer life expectancy. This study examined perioperative and long-term outcomes of young patients undergoing aneurysm repair by either open surgical or endovascular means. METHODS: A retrospective review of a prospectively collated database was performed. Patients undergoing elective aneurysm repair at the age of 65 years or younger between January 2000 and September 2010 were included. All EVAR patients were followed up in a nurse-led clinic. Data regarding long-term outcomes for patients undergoing open repair were gathered from case note review. RESULTS: There were 99 patients who underwent open repair and 59 patients who underwent endovascular repair. Groups were well matched in terms of demographics and co morbidities. 30-day mortality was 1% after open repair. There were no perioperative deaths after endovascular repair. Overall, 30-day complication rates were 15% after open repair and 12% after EVAR. The nature of complications differed between the two groups with the EVAR group experiencing endoleaks and the OAR group demonstrating more cardiorespiratory complications. Mean follow-up was 75.5 months and there was a 14% reintervention rate after EVAR compared with 7% after OAR. CONCLUSION: Young patients are likely to have a lower procedural risk for EVAR and OAR than described in published figures. Although mortality and complication rates in these two groups were similar, the nature of complications occurring following open surgery were often more significant than those occurring after EVAR. There remains a risk of late reintervention following either form of repair. PMID- 24239145 TI - Response to 'left renal vein division during open surgery of abdominal aortic disease: a propensity score-matched case-control study'. PMID- 24239146 TI - Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis. AB - BACKGROUND: The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis. METHODS: Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration. RESULTS: Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P < 0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P < 0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761). CONCLUSION: Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required. PMID- 24239147 TI - Parthenolide inhibits polyethylene particle-induced mouse calvarial osteolysis in vivo. AB - BACKGROUND: Periprosthetic osteolysis and aseptic loosening (AL) after joint arthroplasty are serious problems encountered after an implant surgery. AL is possibly caused by osteolysis or local bone resorption induced by implant-derived wear particles. However, effective treatments for osteoclastic bone resorption and AL mediated by wear particles have not been developed except surgical revision. Therefore, a new strategy should be developed to improve osteolysis associated with AL via pharmacologic intervention. MATERIALS AND METHODS: The effects of parthenolide (PTN), a nuclear factor-kappa B inhibitor and sesquiterpene lactone, on polyethylene particle-induced osteolysis in vivo were investigated using a mouse calvarial model. Bone volume/tissue volume (BV/TV, %), bone surface/bone volume (BS/BV, 1/mm), osteoclast number per bone perimeter (N.Oc/B.Pm, /mm), and eroded surface per bone surface (ES/BS, %) were determined by micro-computed tomography and histologic analyses. RESULTS: Severe bone resorption and rapid osteoclast formation were found in the cranium of the subjects after polyethylene particles were implanted. ES/BS (P < 0.001), N.Oc/B.Pm (group III, P < 0.05; group IV, P < 0.001), and BS/BV (P < 0.001) increased compared with those in group II; BS/BV (P < 0.001) decreased in group II but was improved in groups III and IV, which were treated with PTN. No significant difference in these parameters was observed among groups I, III, and IV. CONCLUSIONS: PTN possibly elicited therapeutic effects on osteolysis induced by wear particles, indicating that PTN could be used as a therapeutic agent of AL induced by wear particles. PMID- 24239148 TI - Immunogenic alteration in laparoscopic common bile duct exploration. AB - BACKGROUND: The immunologic benefits of laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis are poorly understood. The aim of the present study was to investigate immunologic changes during LCBDE using primary suture or T-tube drainage. METHODS: Patients with choledocholithiasis undergoing laparoscopic primary suture of the common bile duct after LCBDE (primary suture group) or laparoscopic LCBDE with choledochotomy plus T-tube drainage (T-tube group) at a single center between June 2008 and June 2011 were included in the present study. Blood samples were collected 24 h preoperatively, and 24 and 72 h postoperatively to assess interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) as inflammation markers. Immunosuppression was evaluated using C reactive protein and leukocyte subpopulations. RESULTS: Patients were 60 +/- 17 y old in the primary suture group (56 men and 76 women) and 54 +/- 20 y old in the T-tube group (50 men and 58 women). In the primary suture group, three patients (2.3%) required open surgery and six (4.5%) developed postoperative bile leakage. In the T-tube group, two patients (1.9%) required open surgery and four (3.7%) had bile leakage. Operation time and hospital stay were shorter in the primary suture group (P < 0.05). Postoperative TNF-alpha and lymphocyte counts were lower, and C-reactive protein and IL-6 levels were higher in the T-tube group compared with the primary suture group (P < 0.05). No recurrences or bile duct strictures were noted during follow-up (median of 12 mo). CONCLUSIONS: Laparoscopic primary suture techniques appear to reduce immunologic suppression by minimizing surgical trauma in patients with choledocholithiasis. PMID- 24239149 TI - Fluid volume overload negatively influences delayed primary facial closure in open abdomen management. AB - BACKGROUND AND AIM: The open abdomen (OA) is associated with significant morbidity and mortality, and its management poses a formidable challenge. Inability to achieve primary closure of the abdominal wall is one of the most severe complications of this technique. Factors influencing primary fascial closure, however, are unknown. This study aims to explore the influence of fluid volume overload on the application of vacuum-assisted and mesh-mediated fascial traction (VAWCM) in OA treatment. METHODS: A review of patients undergoing OA management using VAWCM technique from January 2006 to November 2011 was performed. Patients with aged <18 y OA treatment for fewer than 5 d and abdominal wall hernia before OA treatment were excluded. RESULTS: Average age was 45 +/- 10.1 y and average OA treatment time was 31 +/- 6.8 d. The complete fascial closure rate was 60%. The overall mean bodyweight-based fluid overload was 7.2 kg (range: -8.0 to +21.6 kg), representing a mean percent weight gain of 11.5% (range: -9.5% to +27%). Patients with fluid-related weight gain >=10% had a lower primary facial closure rate than those with <10% (39% versus 77%). And primary facial closure rate seems to further decrease with fluid-related weight gain >=20%, suggesting a dose-response effect of progressive fluid accumulation. CONCLUSIONS: The VAWCM method provided a high primary fascial closure rate after long-term treatment of OA. Fluid volume overload negatively influences delayed primary facial closure. Judicious intravenous fluid resuscitation should be advocated in the therapy of critically ill patients. PMID- 24239150 TI - Relation between alcohol consumption and arterial stiffness: A cross-sectional study of middle-aged Japanese women and men. AB - Epidemiological data indicate the existence of a J-shaped association between alcohol consumption and cardiovascular mobility and mortality. However, studies assessing the relationship between alcohol consumption and pulse wave velocity (PWV) as a marker of arterial stiffness have provided inconsistent results. In addition, data regarding the effect of alcohol on arterial stiffness in women has been limited. This study aimed to clarify the relationship between alcohol consumption and PWV among female and male workers in Japan. Study participants were local government employees in Hokkaido, Japan, who underwent annual health check-ups. All data were collected using self-administered questionnaires. The average daily alcohol consumption of the previous month, based on the alcohol concentration of each beverage type (g/day, ethanol equivalent), was estimated according to the frequency and amount of consumption. Data from 3893 participants (812 women and 3081 men) were analyzed. In women, non-drinkers had significantly higher PWV than women who consumed <10 g/day of alcohol. In men, compared with those who reportedly drank 20-39 g/day, non-drinkers and those who drank <20 g/day and >=60 g/day had significantly higher PWV. Alcohol consumption showed a J shaped association with PWV in men (p for quadratic term < 0.036) and marginally in women (p < 0.056). The results of stratified analyses by age groups showed a significant J-shaped association, which was most notable for men >=45 years (p < 0.005). In middle-aged Japanese women and men, light-to-moderate alcohol consumption is associated with lower PWV, which in turn correlates with a reduction in vascular stiffness. PMID- 24239151 TI - Associations between heavy alcohol drinking and lipid-related indices in middle aged men. AB - The ratio of triglycerides to HDL cholesterol (TG/HDL-C ratio) and lipid accumulation product (LAP: a continuous marker of lipid over-accumulation determined by waist circumference and triglycerides) have been proposed to be good predictors of cardiovascular disease. The aim of this study was to clarify the relationships between heavy alcohol drinking and lipid-related indices including TG/HDL-C ratio, LAP, and ratio of LDL cholesterol to HDL cholesterol (LDL-C/HDL-C ratio). The subjects were middle-aged male nondrinkers and heavy drinkers (ethanol intake: >=66 g per drinking day, which is 2-3 times or more than the generally recommended border level of daily alcohol consumption of 20-30 g). The levels of each lipid-related index after adjustment for age, smoking, and regular exercise were compared among nondrinkers, occasional heavy drinkers, and regular heavy drinkers. Log-transformed TG/HDL-C ratio was significantly higher in occasional heavy drinkers (mean +/- standard error: 0.445 +/- 0.014) than in nondrinkers (0.388 +/- 0.004) and regular heavy drinkers (0.359 +/- 0.013), and was not significantly different in nondrinkers and regular heavy drinkers. Log transformed LAP was significantly higher in occasional heavy drinkers (1.51 +/- 0.02) and regular heavy drinkers (1.44 +/- 0.02) than in nondrinkers (1.34 +/- 0.01), and was significantly higher in occasional heavy drinkers than in regular heavy drinkers. LDL-C/HDL-C ratio was significantly lower in occasional heavy drinkers (2.41 +/- 0.04) and regular heavy drinkers (1.72 +/- 0.04) than in nondrinkers (2.62 +/- 0.01) and was significantly lower in regular heavy drinkers than in occasional heavy drinkers. Results of logistic regression analysis, using odds ratios for high lipid indices of occasional or regular heavy drinkers vs. nondrinkers, agreed with the above results of analysis of covariance. Occasional heavy drinkers showed more detrimental and less favorable levels of the lipid indices than did regular heavy drinkers, and thus heavy drinking, even if occasional, should be avoided to prevent cardiovascular disease. PMID- 24239153 TI - Risk scoring and thromboprophylactic treatment of patients with atrial fibrillation with and without access to primary healthcare data: experience from the Stockholm health care system. AB - BACKGROUND: Earlier validation studies of risk scoring by CHA2DS2VASc for assessments of appropriateness of warfarin treatment in patients with atrial fibrillation have been performed solely with diagnoses recorded in hospital based care, even though many patients to a large extent are managed in primary care. METHODS: Cross-sectional registry study of all 43 353 patients with a diagnosis of non-valvular atrial fibrillation recorded in inpatient care, specialist ambulatory care or primary care in the Stockholm County during 2006-2010. RESULTS: The mean CHA2DS2VASc score was 3.82 (4.67 for women and 3.14 for men). 64% of the entire cohort of patients with atrial fibrillation had the diagnosis in primary care (12% only there). The mean CHA2DS2VASc score of patients with a diagnosis only in inpatient care or specialist ambulatory care increased from 3.63 to 3.83 when comorbidities registered in primary care were added. In 2010 warfarin prescriptions were claimed by 47.2%, and ASA by 41.6% of the entire cohort. 34% of patients with CHA2DS2VASc=1 and 20% with CHA2DS2VASc=0 had warfarin treatment. ASA was more frequently used instead of warfarin among women and elderly patients. CONCLUSIONS: Registry CHA2DS2VASc scores were underestimated without co-morbidity data from primary care. Many individuals with scores 0 and 1 were treated with warfarin, despite poor documentation of clinical benefit. In contrast, warfarin appears to be underused and ASA overused among high risk atrial fibrillation patients. Lack of diagnoses from primary care underestimated CHA2DS2VASc scores and may thereby have overestimated treatment benefits in low-risk patients in earlier studies. PMID- 24239152 TI - Transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium. AB - BACKGROUND: A persistent anastomosis between the pulmonary veins that connect with the left atrium and the systemic vein that drains into the right atrium has occasionally been reported. We report characteristics and transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium. METHODS: We retrospectively studied such patients in 5 institutions. RESULTS: Ten patients (6 girls) presented at a median age of 8 (0.1 to 54) years with 2 anatomic types: 8 vertical vein types with drainage of the left upper lobe to the innominate vein via a large vertical vein (left superior cardinal vein) and to the left atrium via the left upper pulmonary vein; and 2 scimitar vein (SV) types with drainage of the right middle and lower pulmonary veins into the inferior vena cava and to the left atrium via an anomalous connecting vein. Associated malformations were aortic coarctation (n=2) and secundum atrial septal defects (n=3). Two patients of the vertical vein type were operated. Transcatheter occlusion of the abnormal pulmonary venous return was performed in 7 cases, associated with occlusion of systemic arterial supply (n=2), secundum atrial septal closure (n=2), left upper pulmonary vein stenosis stenting (n=1), and coarctation stenting (n=1). Including previously published cases, 18 patients (13 vertical veins and 5 scimitar veins) underwent transcatheter repair. Patients over 40 years of age tend to be symptomatic at presentation (p=0.056). CONCLUSION: In partially abnormal pulmonary venous return with dual drainage, transcatheter therapy can be offered in the majority of patients. PMID- 24239154 TI - One-year results of the randomized, controlled, short-term psychotherapy in acute myocardial infarction (STEP-IN-AMI) trial. AB - BACKGROUND: Previous studies on cognitive and interpersonal interventions have yielded inconsistent results in ischemic heart disease patients. METHODS: 101 patients aged <= 70 years, and enrolled one week after complete revascularization with urgent/emergent angioplasty for an AMI, were randomized to standard cardiological therapy plus short-term humanistic-existential psychotherapy (STP) versus standard cardiological therapy only. Primary composite end point was: one year incidence of new cardiological events (re-infarction, death, stroke, revascularization, life-threatening ventricular arrhythmias, and the recurrence of typical and clinically significant angina) and of clinically significant new comorbidities. Secondary end points were: rates for individual components of the primary outcome, incidence of re-hospitalizations for cardiological problems, New York Heart Association class, and psychometric test scores at follow-up. RESULTS: 94 patients were analyzed at one year. The two treatment groups were similar across all baseline characteristics. At follow-up, STP patients had had a lower incidence of the primary endpoint, relative to controls (21/49 vs. 35/45 patients; p=0.0006, respectively; NNT=3); this benefit was attributable to the lower incidence of recurrent angina and of new comorbidities in the STP group (14/49 vs. 22/45 patients, p=0.04, NNT=5; and 5/49 vs. 25/45, p<0.0001, NNT=3, respectively). Patients undergoing STP also had statistically fewer re hospitalizations, a better NYHA class, higher quality of life, and lower depression scores. CONCLUSION: Adding STP to cardiological therapy improves cardiological symptoms, quality of life, and psychological and medical outcomes one year post AMI, while reducing the need for re-hospitalizations. Larger studies remain necessary to confirm the generalizability of these results. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT00769366. PMID- 24239155 TI - Cardiac resynchronisation therapy optimisation strategies: systematic classification, detailed analysis, minimum standards and a roadmap for development and testing. AB - In this article an international group of CRT specialists presents a comprehensive classification system for present and future schemes for optimising CRT. This system is neutral to the measurement technology used, but focuses on little-discussed quantitative physiological requirements. We then present a rational roadmap for reliable cost-effective development and evaluation of schemes. A widely recommended approach for AV optimisation is to visually select the ideal pattern of transmitral Doppler flow. Alternatively, one could measure a variable (such as Doppler velocity time integral) and "pick the highest". More complex would be to make measurements across a range of settings and "fit a curve". In this report we provide clinicians with a critical approach to address any recommendations presented to them, as they may be many, indistinct and conflicting. We present a neutral scientific analysis of each scheme, and equip the reader with simple tools for critical evaluation. Optimisation protocols should deliver: (a) singularity, with only one region of optimality rather than several; (b) blinded test-retest reproducibility; (c) plausibility; (d) concordance between independent methods; and (e) transparency, with all steps open to scrutiny. This simple information is still not available for many optimisation schemes. Clinicians developing the habit of asking about each property in turn will find it easier to win now down the broad range of protocols currently promoted. Expectation of a sophisticated enquiry from the clinical community will encourage optimisation protocol-designers to focus on testing early (and cheaply) the basic properties that are vital for any chance of long term efficacy. PMID- 24239156 TI - Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia. AB - BACKGROUND: Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia. METHODS: A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n=15), two groups receiving orally administered rosuvastatin (10 and 20mg/daily for 30 days; n=16 for each group), a group receiving BPF alone orally (1000 mg/daily for 30 days; n=15) and a group receiving BPF (1000 mg/daily given orally) plus rosuvastatin (10mg/daily for 30 days; n=15). RESULTS: Both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accompanied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells. CONCLUSIONS: Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy. PMID- 24239157 TI - Review: where is the maternofetal interface? AB - Ask where the maternofetal interface is and placental biologists will tell you, the syncytiotrophoblast and extravillous cytotrophoblasts. While correct, this is not full extent of the maternofetal interface. Trophoblast debris that is extruded into the maternal blood in all pregnancies expands the maternofetal interface to sites remote from the uterus. Trophoblast debris ranges from multinucleated syncytial nuclear aggregates to subcellular micro- and nano vesicles. The origins of trophoblast debris are not clear. Some propose trophoblast debris is the end of the life-cycle of the trophoblast and that it results from an apoptosis-like cell death, but this is not universally accepted. Knowing whether trophoblast debris results from an apoptosis-like cell death is important because the nature of cell death that produced trophoblast debris will influence the maternal responses to it. Trophoblast debris is challenging to isolate from maternal blood making it difficult to study. However, by culturing placental explants in NetwellsTM we can readily harvest trophoblast debris from beneath the NetwellsTM which is very similar to debris that has been isolated from pregnant women. We have found that trophoblast debris from normal placentae shows markers of apoptosis and is phagocytosed by macrophages or endothelial cells, producing a tolerant phenotype in the phagocyte. Whereas, when we culture normal placental explants with factors such as antiphospholipid antibodies (a strong maternal risk factor for preeclampsia), or IL-6 (which is found at increased levels in the sera of preeclamptic women), the death process in the syncytiotrophoblast changes, such that the trophoblast debris becomes more necrotic. Phagocytosis of this necrotic debris leads to activation of endothelial cells. Trophoblast debris greatly expands the maternofetal interface and the nature of that debris is likely to strongly influence the responses of the maternal vascular and immune systems to the debris. PMID- 24239158 TI - Assessment of therapeutic efficacy of miR-126 with contrast-enhanced ultrasound in preeclampsia rats. AB - Preeclampsia is a pregnancy-specific syndrome characterized by high blood pressure and proteinuria, which has a pathophysiology of insufficient placental blood perfusion. MicroRNA-126 (miR-126), an angiogenesis-related miRNA, has been proved to play a significant role in endothelial cells response to ischemia in vitro and in vivo. However, whether miR-126 has therapeutic potential in vasculogenesis of preeclampsia placenta remains uncertain. In this study, we focused our attention on this unsolved problem. First, we established the preeclampsia animal model and over-expressed miR-126 in vivo using a specific agomir. Then we described the effects of miR-126 on placental vasculogenesis in preeclampsia rats, including the evaluation of placental blood perfusion using microbubbles-assisted contrast-enhanced ultrasonography (CEUS), placental histology, immunohistochemistry and pregnancy outcome. Finally, we investigated the possible target gene and pathway that miR-126 modulates. Together, our results showed that preeclampsia animal with over-expressed miR-126 had higher pup weight, placenta weight and proportion of live pups. Quantification of uteroplacental perfusion by CEUS and CD34 staining of placental tissue revealed that blood volume and microvessel density increased in miR-126 treated group. MiR 126 was related to PIK3R2 down-regulation and Akt activation within placenta, which had impacts on vascularization of placenta. Therefore, miR-126 may be an efficient gene therapy to promote angiogenesis and blood perfusion in preeclampsia placenta. PMID- 24239159 TI - Involvement of CRH and hCG in the induction of aromatase by cortisol in human placental syncytiotrophoblasts. AB - INTRODUCTION: Increased estrogen production in placenta towards the end of gestation plays a pivotal role in the onset of human labor. Estrogen transforms myometrium from a quiescent to a contractile status. Glucocorticoids have been shown to induce estrogen production through the transcription factor specificity protein 1 (Sp1)-mediated induction of aromatase transcription upon elevation of cyclic adenosine mono-phosphate (cAMP) level in human placental syncytiotrophoblasts. However, it is unclear how glucocorticoids activate cAMP pathway thereby inducing aromatase expression in human placental syncytiotrophoblasts. MATERIAL AND METHODS: We investigated this issue in cultured primary human placental syncytiotrophoblasts prepared from placentas collected at term without labor. RESULTS: We demonstrated that cortisol (0.01-1 MUM) dose-dependently increased corticotropin-releasing hormone (CRH) and human chorionic gonadotropin (hCG) alpha/beta subunit expression and their production in the syncytiotrophoblasts. The induction of intracellular cAMP level, Sp1 expression, Sp1 enrichment at the aromatase promoter as well as aromatase expression by cortisol could be partially attenuated by either hCG antibody (1:100) or CRH receptor antagonist alpha-helical-CRH (1 MUM), and further attenuated by combination of hCG antibody and alpha-helical-CRH. CONCLUSIONS: Cortisol increases aromatase expression via induction of CRH and hCG production and subsequent elevation of cAMP level and enrichment of Sp1 at the aromatase promoter in human placental syncytiotrophoblasts. These findings may account for the parallel increases of cortisol and estrogen production prior to the onset of parturition. PMID- 24239160 TI - Periconceptional alcohol consumption causes fetal growth restriction and increases glycogen accumulation in the late gestation rat placenta. AB - INTRODUCTION: Alcohol consumption is a common social practice among women of childbearing age. With 50% of pregnancies being unplanned, many embryos are exposed to alcohol prior to pregnancy recognition and formation of the placenta. The effects of periconceptional (PC) alcohol exposure on the placenta are unknown. METHODS: Sprague-Dawley rats were exposed to alcohol (12.5% v/v ad libitum) from 4 days prior to 4 days after conception and effects on placental growth, morphology and gene/protein expression examined at embryonic day (E) 20. RESULTS: PC ethanol (EtOH)-exposed fetuses were growth restricted and their placental/body weight ratio and placental cross-sectional area were increased. This was associated with an increase in cross-sectional area of the junctional zone and glycogen cells, especially in PC EtOH-exposed placentas from female fetuses. Junctional Glut1 and Igf2 mRNA levels were increased. Labyrinth Igf1 mRNA levels were decreased in placentas from both sexes, but protein IGF1R levels were decreased in placentas from male fetuses only. Labyrinth mRNA levels of Slc38a2 were decreased and Vegfa were increased in placentas following PC EtOH exposure but only placentas from female fetuses exhibited increased Kdr expression. Augmented expression of the protective enzyme 11betaHsd2 was found in PC EtOH-exposed labyrinth. DISCUSSION: These observations are consistent with a stress response, apparent well beyond the period of EtOH-exposure and demonstrate that PC EtOH alters placental development in a sex specific manner. CONCLUSION: Public awareness should be increased to educate women about how excessive drinking even before falling pregnant may impact on placental development and fetal health. PMID- 24239162 TI - Retinal arteriole-to-venule ratio changes and target organ disease evolution in newly diagnosed hypertensive patients at 1-year follow-up. AB - There is no agreement on the systematic exploration of the fundus oculi (FO) in hypertensive patients, and it is unknown whether the evolution of retinal microcirculatory alterations has prognostic value or not. The aim of this study was to investigate whether the evolution of the arteriole-to-venule ratio (AVR) in newly-diagnosed hypertensive patients is associated with better or worse evolution of target organ damage (TOD) during 1 year. A cohort of 133 patients with newly-diagnosed untreated hypertension was followed for 1 year. At baseline and follow-up, all patients underwent a physical examination, self-blood pressure measurement, ambulatory blood pressure monitoring, blood and urine analysis, electrocardiogram, and retinography. The endpoint was the favourable evolution of TOD and the total amount of TOD, according to the baseline AVR and the baseline and final difference of the AVR. A total of 133 patients were analyzed (mean age, 57 +/- 10.7 years; 59% men). No differences were found in the decrease in blood pressure or antihypertensive treatment between quartiles of baseline AVR or baseline-final AVR difference. Patients with a difference between baseline and final AVR in the highest quartile (>0.0817) had a favorable evolution of left ventricular hypertrophy (odds ratio, 14.9; 95% confidence interval, 1.08-206.8) and the amount of TOD (odds ratio, 2.22; 95% confidence interval, 1.03-6.05). No favorable evolution was found of glomerular filtration rate. There is an association between the evolution of the AVR and the favorable evolution of TOD. Patients with greater increase of AVR have significantly better evolution of left ventricular hypertrophy and amount of TOD. PMID- 24239161 TI - Semen quality and time to pregnancy: the Longitudinal Investigation of Fertility and the Environment Study. AB - OBJECTIVE: To assess semen parameters and couple fecundity as measured by time to pregnancy (TTP). DESIGN: Observational prospective cohort with longitudinal measurement of TTP. SETTING: Sixteen Michigan/Texas counties. PATIENT(S): A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided two samples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Using prospectively measured TTP, fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for 36 individual semen quality parameters accounting for repeated semen samples, time off contraception, abstinence, enrollment site, and couples' ages, body mass indices, and serum cotinine concentrations. RESULT(S): In adjusted models, semen quality parameters were associated with significantly shorter TTP as measured by FORs >1: percent motility, strict and traditional morphology, sperm head width, elongation factor, and acrosome area. Significantly longer TTPs or FORs <1 were observed for morphologic categories amorphous and round sperm heads and neck/midpiece abnormalities. No semen quality parameters achieved significance when simultaneously modeling all other significant semen parameters and covariates, except for percent coiled tail when adjusting for sperm concentration (FOR 0.99; 95% CI 0.99-1.00). Male age was consistently associated with reduced couple fecundity (FOR 0.96; 95% CI 0.93-0.99), reflecting a longer TTP across all combined models. Female but not male body mass index also conferred a longer TTP (FOR 0.98; 95% CI 0.96-0.99). CONCLUSION(S): Several semen measures were significantly associated with TTP when modeled individually but not jointly and in the context of relevant couple-based covariates. PMID- 24239164 TI - Influence of fatigue on upper limb muscle activity and performance in tennis. AB - The study examined the fatigue effect on tennis performance and upper limb muscle activity. Ten players were tested before and after a strenuous tennis exercise. Velocity and accuracy of serve and forehand drives, as well as corresponding surface electromyographic (EMG) activity of eight upper limb muscles were measured. EMG and force were also evaluated during isometric maximal voluntary contractions (IMVC). Significant decreases were observed after exercise in serve accuracy (-11.7%) and velocity (-4.5%), forehand accuracy (-25.6%) and consistency (-15.6%), as well as pectoralis major (PM) and flexor carpi radialis (FCR) IMVC strength (-13.0% and -8.2%, respectively). EMG amplitude decreased for PM and FCR in serve, forehand and IMVC, and for extensor carpi radialis in forehand. No modification was observed in EMG activation timing during strokes or in EMG frequency content during IMVC. Several hypotheses can be put forward to explain these results. First, muscle fatigue may induce a reduction in activation level of PM and forearm muscles, which could decrease performance. Second, conscious or subconscious strategies could lead to a redistribution of muscle activity to non-fatigued muscles in order to protect the organism and/or limit performance losses. Otherwise, the modifications of EMG activity could also illustrate the strategies adopted to manage the speed-accuracy trade-off in such a complex task. PMID- 24239163 TI - Compensatory cellular hypertrophy: the other strategy for tissue homeostasis. AB - Metazoan tissues have the ability to maintain tissue size and morphology while eliminating aberrant or damaged cells. In the tissue homeostasis system, cell division is the primary strategy cells use not only to increase tissue size during development but also to compensate for cell loss in tissue repair. Recent studies in Drosophila, however, have shown that cells in postmitotic tissues undergo hypertrophic growth without division, contributing to tissue repair as well as organ development. Indeed, similar compensatory cellular hypertrophy (CCH) can be observed in different contexts such as mammalian hepatocytes or corneal endothelial cells. Here we highlight these findings and discuss the underlying mechanisms of CCH, which is likely an evolutionarily conserved strategy for homeostatic tissue growth in metazoans. PMID- 24239165 TI - Expression of fibroblast growth factor 9 is associated with poor prognosis in patients with resected non-small cell lung cancer. AB - OBJECTIVES: Fibroblast growth factor (FGF) 9 is a member of the FGF family, which modulates cell proliferation, differentiation, and motility. Recent studies show that the activation of FGF signals including FGF9 is associated with the pathogenesis of several cancers; however, its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to clarify the characteristics of NSCLC with FGF9 expression. MATERIALS AND METHODS: We evaluated the expression of FGF9 in resected NSCLC specimens and corresponding non-tumorous lung tissue samples using cDNA microarray and evaluated its clinicopathological characteristics. RESULTS: Nine out of 90 NSCLC specimens (10%) had "high" FGF9 expression compared with corresponding non-cancerous lung tissues. Histologically, of the 9 NSCLC specimens with high FGF9 expression, 5 were adenocarcinoma, whereas none were squamous cell carcinoma. FGF9 expression was not associated with sex, smoking history, or clinical stage. However, in patients with high and low FGF9 expression, the postoperative recurrence rates were 78% and 24% (p=0.033), respectively. Overall survival was significantly shorter in patients with high FGF9 expression than in those with low FGF9 expression (p<0.001). CONCLUSION: Our data indicate that FGF9 may be a novel unfavorable prognostic indicator and a candidate therapeutic target of NSCLC. PMID- 24239168 TI - Immediate effect of walking with talus-stabilizing taping on ankle kinematics in subjects with limited ankle dorsiflexion. AB - OBJECTIVE: To determine the effects of walking with talus-stabilizing taping (TST) on ankle dorsiflexion (DF) and heel-off time in the stance phase of gait and ankle DF passive range of motion (PROM). DESIGN: Pre- and post-intervention study. SETTING: University motion analysis laboratory. PARTICIPANTS: Ten subjects participated in this study. Sixteen ankles with limited ankle DF PROM were tested. MAIN OUTCOME MEASURES: Ankle DF PROM was measured using a goniometer, and maximum ankle DF before heel-off and time to heel-off in the stance phase of gait were measured using a 3D motion analysis system before and after walking with TST. Data were analyzed using a paired t-test. RESULTS: Ankle maximum DF before heel-off (p = 0.001), time to heel-off during the stance phase of gait (p = 0.005), and ankle DF PROM (p < 0.001) were significantly increased post intervention compared with pre-intervention. CONCLUSIONS: Walking with TST is an effective self-exercise for improving ankle kinematics during gait and increasing ankle DF PROM in individuals with limited ankle DF PROM. PMID- 24239167 TI - The effect of Xbox Kinect intervention on balance ability for previously injured young competitive male athletes: a preliminary study. AB - OBJECTIVES: To explore the outcomes of an Xbox Kinect intervention on balance ability, enjoyment and compliance for previously injured young competitive male athletes. DESIGN: Experimental pre-/post-test design with random assignment. PARTICIPANTS: Sixty-three previously injured young competitive male athletes, aged 16 +/- 1 years. INTERVENTIONS: Participants were divided into three groups: one group received Xbox Kinect (XbK) training, one group received Traditional physiotherapy (TP) training, and one group did not receive any balance training (Control). Intervention involved a 24 min session, twice weekly for 10 weeks. MAIN OUTCOME MEASURES: Overall stability index (OSI) and limits of stability (LOS) scores using the Biodex Stability System. Enjoyment using the Physical Activity Enjoyment Scale. Self-reported compliance. RESULTS: Both experimental groups demonstrated an improvement in OSI and LOS mean scores for the right and the left limb after the intervention. In addition, the results revealed important differences between the experimental groups and the control group on balance test indices. Group enjoyment rating was greater for XbK compared with TP, while the compliance rating was not. CONCLUSIONS: These findings suggest that the use of XbK intervention is a valuable, feasible and pleasant approach in order to improve balance ability of previously injured young competitive male athletes. PMID- 24239169 TI - Clinically relevant multidrug resistant Salmonella enterica in swine and meat handlers at the abattoir. AB - The presence of multidrug resistant (MDR) Salmonella serotypes in slaughtered swine, carcasses, meat and meat handlers is scarcely evaluated. Recently we demonstrated that diverse Salmonella serotypes are frequently present in swine, pork meat and carcasses, and meat handlers at Portuguese abattoirs. Here we have characterized their antibiotic resistance phenotypes and genotypes, helping elucidate the flow of MDR Salmonella in the food chain. Testing 60 Salmonella isolates from different serotypes, the highest frequencies of resistance were observed for tetracycline (T) [70% (n=42/60), tet(A)/tet(B)/tet(G)], streptomycin (S) [63% (n=38/60), aadA2/strA/strB], sulfamethoxazole (Sul) [62% (n=37/60), sul1/sul2/sul3] and ampicillin (A) [57% (n=34/60), blaPSE-1/blaTEM]. Thirty-seven percent (n=22/60) carried class 1 integrons and multidrug resistance was frequently observed (63% n=38/60), including those serotypes common to human infections [S. Typhimurium 78% n=25/32; S. 4,[5],12:i:- 67% n=2/3; S. Rissen 75% (n=3/4); S. London 67% n=2/3; S. Derby 55%; n=6/11)]. The emergent S. 4,[5],12:i: isolates were mostly characterized by ASSuT phenotype [blaTEM/strA strB/sul2/tet(B)], typical of the European clone, while for the first time the ST phenotype [strA-strB-tet(A)-tet(B)] was also observed. Moreover, we report a first finding of a MDR phenotype in S. London [ANSSuT; blaTEM-strA-strB-sul2 tet(A)]. Our findings suggest that the abattoir environment and the slaughter operations seem not only to harbor MDR serotypes that originated in the pig reservoir, but also propagate them through cross-contamination processes, involving meat handlers. The present study suggests a probable relationship between swine and human salmonellosis throughout the food chain, which is of interest for epidemiological, animal health and public health purposes. PMID- 24239170 TI - A serological survey of canine H3N2, pandemic H1N1/09 and human seasonal H3N2 influenza viruses in dogs in China. AB - Influenza viruses have been isolated from dogs in China; however, the extent of influenza infection among dogs is not yet clear. Here, we examined the seroprevalence of avian-origin canine H3N2, pandemic H1N1/09 and human seasonal H3N2 influenza viruses in pet dogs in China during January 2012 to June 2013. The seropositivity rate of canine H3N2, H1N1/09 and human H3N2 were 3.5%, 1.5%, and 1.2%, respectively. Dogs aged 2-5 years were most commonly seropositive to canine H3N2 virus. It is worth noting that two serum samples were positive against both canine H3N2 and H1N1/09 viruses, suggesting the possibility of coinfection with both viruses. Our findings emphasize the necessity for continued surveillance of influenza viruses in dogs in China. PMID- 24239171 TI - Growing matter: a review of growth in living systems. AB - Living systems can grow, develop, adapt, and evolve. These phenomena are non intuitive to traditional engineers and often difficult to understand. Yet, classical engineering tools can provide valuable insight into the mechanisms of growth in health and disease. Within the past decade, the concept of incompatible configurations has evolved as a powerful tool to model growing systems within the framework of nonlinear continuum mechanics. However, there is still a substantial disconnect between the individual disciplines, which explore the phenomenon of growth from different angles. Here we show that the nonlinear field theories of mechanics provide a unified concept to model finite growth by means of a single tensorial internal variable, the second order growth tensor. We review the literature and categorize existing growth models by means of two criteria: the microstructural appearance of growth, either isotropic or anisotropic; and the microenvironmental cues that drive the growth process, either chemical or mechanical. We demonstrate that this generic concept is applicable to a broad range of phenomena such as growing arteries, growing tumors, growing skin, growing airway walls, growing heart valve leaflets, growing skeletal muscle, growing plant stems, growing heart valve annuli, and growing cardiac muscle. The proposed approach has important biological and clinical applications in atherosclerosis, in-stent restenosis, tumor invasion, tissue expansion, chronic bronchitis, mitral regurgitation, limb lengthening, tendon tear, plant physiology, dilated and hypertrophic cardiomyopathy, and heart failure. Understanding the mechanisms of growth in these chronic conditions may open new avenues in medical device design and personalized medicine to surgically or pharmacologically manipulate development and alter, control, or revert disease progression. PMID- 24239172 TI - New orally active proteasome inhibitors in multiple myeloma. AB - Bortezomib is the first proteasome inhibitor approved for the therapy of multiple myeloma (MM). Although Bortezomib has renovated the treatment of MM, a considerable proportion of subjects fail to respond to Bortezomib treatment and almost all patients relapse from this drug either alone or when used in combination therapies. However, the good clinical outcome of Bortezomib treatment in MM patients gave impulsion for the development of second generation proteasome inhibitors with the ambition of improving efficacy of proteasome inhibition, enhancing antitumor activity, and decreasing toxicity, as well as providing flexible dosing schedules and patient convenience. This review provides an overview of the role of oral proteasome inhibitors including Marizomib, Oprozomib, Delanzomib, chemical proteasome inhibitors, and cinnabaramides, in the therapy of MM, focusing on developments over the past five years. These emerging drugs with different mechanisms of action have exhibited promising antitumor activity in patients with relapsed/refractory MM, and they are creating chances to target multiple pathways, overcome resistance, and improve clinical outcomes, mainly for those subjects who are refractory to approved agents. Future steps in the clinical development of oral inhibitors include the optimization of the schedule and the definition of their antitumor activity in MM. PMID- 24239173 TI - By inhibiting Src, verapamil and dasatinib overcome multidrug resistance via increased expression of Bim and decreased expressions of MDR1 and survivin in human multidrug-resistant myeloma cells. AB - The calcium channel blocker verapamil inhibits the transport function of multidrug resistance protein 1 (MDR1). Although verapamil acts to reverse MDR in cancer cells, the underlying mechanism remains unclear. In the present study, we investigated the mechanism of reversing MDR by verapamil in anti-cancer drug resistant multiple myeloma (MM) cell lines. We found that verapamil suppresses MDR1 and survivin expressions and increases Bim expression via suppression of Src activation. Furthermore, dasatinib reversed the drug-resistance of the drug resistant cell lines. These findings suggest that Src inhibitors are potentially useful as an anti-MDR agent for the treatment of malignant tumor cells. PMID- 24239174 TI - Has introduction of azacytidine in everyday clinical practice improved survival in late-stage Myelodysplastic syndrome? A single center experience. AB - Data derived from clinical trials consistently show a prolongation of overall survival of late-stage MDS patients with the introduction of azacytidine. Nevertheless, the applicability of the above results to real-world clinical settings may be questionable due to the strict design, the controlled medical environment, and the limited patient sample of explanatory studies. We retrospectively compared the outcome of two well-balanced groups of late-stage MDS patients. The first consisted of 46 patients treated with azacytidine (AZA cohort) and the second of 41 patients treated with other agents (non-AZA cohort). Patients in the AZA cohort displayed superior survival compared to the non-AZA ones. However, subgroup analysis revealed that azacytidine conferred a significant survival advantage only in patients with AML-MDS and those who attained a CR at any time after treatment initiation, while all other patients displayed comparable outcome with the non-AZA cohort. Larger series are needed to determine which patients benefit most from azacytidine therapy. PMID- 24239175 TI - High CXCR4 and low VLA-4 expression predicts poor survival in adults with acute lymphoblastic leukemia. AB - Data regarding the prognostic significance of CXCR4 and VLA-4 in ALL are limited. Especially, VLA-4 has not been evaluated at the time of diagnosis in both adult and childhood ALL patients. We prospectively analyzed the expression of VLA-4 and CXCR4 in 54 patients (VLA-4 in 29 adults and 25 children and CXCR4 in 22 adults and 24 children) newly diagnosed with ALL by flow cytometry. Expression levels of VLA-4 and CXCR4 were not different between adults and children with ALL. High CXCR4 and low VLA-4 expression each correlated with worse prognosis in adults; patients with high CXCR4 expression had shorter disease-free survival (p=0.01) and overall survival (p=0.04) and patients with low VLA-4 expression had shorter disease-free survival (p=0.02). Expression levels of CXCR4 and VLA-4 did not predict patient prognosis in children. Analysis of CXCR4 and VLA-4 expression at diagnosis in adults with ALL can provide useful information on patient prognosis. PMID- 24239176 TI - IMiDs: Not for the CRBN weak. PMID- 24239177 TI - Human HOX gene disorders. AB - The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies. PMID- 24239178 TI - Holocarboxylase synthetase acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7. AB - In human cells, HCS catalyzes the biotinylation of biotin-dependent carboxylases and mediates the transcriptional control of genes involved in biotin metabolism through the activation of a cGMP-dependent signal transduction pathway. HCS also targets to the cell nucleus in association with lamin-B suggesting additional gene regulatory functions. Studies from our laboratory in Drosophila melanogaster showed that nuclear HCS is associated with heterochromatin bands enriched with the transcriptionally repressive mark histone 3 trimethylated at lysine 9. Further, HCS was shown to be recruited to the core promoter of the transcriptionally inactive hsp70 gene suggesting that it may participate in the repression of gene expression, although the mechanism involved remained elusive. In this work, we expressed HCS as a fusion protein with the DNA-binding domain of GAL4 to evaluate its effect on the transcription of a luciferase reporter gene. We show that HCS possesses transcriptional repressor activity in HepG2 cells. The transcriptional function of HCS was shown by in vitro pull down and in vivo co immunoprecipitation assays to depend on its interaction with the histone deacetylases HDAC1, HDAC2 and HDAC7. We show further that HCS interaction with HDACs and its function in transcriptional repression is not affected by mutations impairing its biotin-ligase activity. We propose that nuclear HCS mediates events of transcriptional repression through a biotin-independent mechanism that involves its interaction with chromatin-modifying protein complexes that include histone deacetylases. PMID- 24239179 TI - Hypodermal metastasis of malignant melanoma to the cheek. AB - INTRODUCTION: On the basis of a case of hypodermal metastasis of malignant melanoma to the cheek and a review of the literature, we analyze treatment and recent progress in metastatic malignant melanoma. CASE-REPORT: A 55-year-old woman presented with a facial hypodermal metastasis of a slow-growing melanoma of the ankle that had been treated by surgery. DISCUSSION/CONCLUSION: Metastatic malignant melanoma treatment, which was usually palliative when surgical resection was not feasible, has been improved by innovations in immunotherapy (ipilimumab) and targeted therapy (vemurafenib). Genetic profiling is an interesting line of research to improve short-term prognosis in these tumors. PMID- 24239180 TI - Malignant head/neck paragangliomas. Comparative study. AB - BACKGROUND: The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics, their natural history and their treatment with those of a series of 131 benign paragangliomas. PATIENTS AND METHODS: Retrospective analysis of 142 patients with head and neck paraganglioma managed between 2001 and 2008. Age at the time of diagnosis, gender, primary tumour site, presence of other non-head/neck paragangliomas and/or metastases diagnosed by imaging (CT, MRI, Octreoscan or (18)F-FDG PET), histology, urinary catecholamine and metanephrine levels, family history, and genetic test results were recorded. RESULTS: This series comprised 131 benign head and neck paragangliomas, mostly observed in women with a mean age at diagnosis of 45 years and a predominance of tympanojugular sites (followed by carotid and vagal sites) with 5% of secreting tumours and 20% of multifocal tumours. Eleven patients (7.7%) with a 1:1 sex ratio presented criteria of malignancy. These patients, with a lower mean age (38 years), predominantly presented carotid lesions with a higher rate of secreting and multifocal tumours, 27% and 46% respectively. The main sites of metastases were bone and lymph nodes. No tympanic paragangliomas were observed. CONCLUSIONS: Malignant paragangliomas are mainly observed in young patients with multifocal tumours, particularly carotid tumours, and are predominantly related to subunit SDH-B mutation. The work-up in these high-risk patients must include whole body scintigraphy and spine MRI. Malignancy is not necessarily associated with a poor short-term prognosis due to the slow course of the disease. PMID- 24239181 TI - Suprazero cooling rate, rather than freezing rate, determines post thaw quality of rhesus macaque sperm. AB - Sperm become most sensitive to cold shock when cooled from 37 degrees C to 5 degrees C at rates that are too fast or too slow; cold shock increases the susceptibility to oxidative damage owing to its influence on reactive oxygen species (ROS) production, which are significant stress factors generated during cooling and low temperature storage. In addition, ROS may be a main cause of decreased motility and fertility upon warming. They have been shown to change cellular function through the disruption of the sperm plasma membrane and through damage to proteins and DNA. The objective of this study was to determine which cryopreservation rates result in the lowest degree of oxidative damage and greatest sperm quality. In the rhesus model, it has not been determined whether suprazero cooling or subzero freezing rates causes a significant amount of ROS damage to sperm. Semen samples were collected from male rhesus macaques, washed, and resuspended in TEST-yolk cryopreservation buffer to 100 * 10(6) sperm/mL. Sperm were frozen in 0.5-mL straws at four different combinations of suprazero and subzero rates. Three different suprazero rates were used between 22 degrees C and 0 degrees C: 0.5 degrees C/min (slow), 45 degrees C/min (medium), and 93 degrees C/min (fast). These suprazero rates were used in combination with two different subzero rates for temperatures 0 degrees C to -110 degrees C: 42 degrees C/min (medium) and 87 degrees C/min (fast). The different freezing groups were as follows: slow-med (SM), slow-fast (SF), med-med (MM), and fast fast (FF). Flow cytometry was used to detect lipid peroxidation (LPO), a result of ROS generation. Motility was evaluated using a computer assisted sperm motion analyzer. The MM and FF treated sperm had less viable (P < 0.0001) and motile sperm (P < 0.001) than the SM, SF, or fresh sperm. Sperm exposed to MM and FF treatments demonstrated significantly higher oxidative damage than SM, SF, or fresh sperm (P < 0.05). The SM- and SF-treated sperm showed decreased motility, membrane integrity, and LPO compared with fresh semen (P < 0.001). Slow cooling from room temperature promotes higher membrane integrity and motility post thaw, compared with medium or fast cooling rates. Cells exposed to similar cooling rates with differing freezing rates were not different in motility and membrane integrity, whereas comparison of cells exposed to differing cooling rates with similar freezing rates indicated significant differences in motility, membrane integrity, and LPO. These data suggest that sperm quality seems to be more sensitive to the cooling, rather than freezing rate and highlight the role of the suprazero cooling rate in post thaw sperm quality. PMID- 24239182 TI - Curable episodic ataxia? History taking versus advanced diagnostic instruments. PMID- 24239183 TI - Screening for frontal lobe and general cognitive impairment in patients with amyotrophic lateral sclerosis. AB - OBJECTIVES: Cognitive impairment occurs in up to 50% of patients with amyotrophic lateral sclerosis (ALS). Simple tools are required to identify such individuals, as cognitive impairment adversely impacts quality of life and survival. Our objective was to determine the potential utility of the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) in evaluating frontal lobe and general cognitive impairment, respectively. We also assessed the feasibility of screening for cognitive impairment in those patients with advanced physical disability by modifying selected FAB and MoCA subtasks. METHODS: Fifty four consecutive ALS patients were screened; 44 completed the FAB and 39 completed the MoCA. We administered modified tasks to patients with severe hand weakness or dysarthria. The patients were classified as cognitively impaired on each measure based on published cut-off scores of 14.11 on the FAB and 26 on the MoCA. RESULTS: Twenty-one percent and 53% of patients were impaired on the FAB and the MoCA, respectively. Scores from patients receiving modified instructions did not differ from those completing standard versions. There were statistically significant correlations between the MoCA total scores and forced vital capacity (FVC) and ALSFRS-R scores. There was no correlation between these variables and the FAB. CONCLUSIONS: Both the FAB and MoCA detected cognitive impairment in ALS patients. While the MoCA classified more patients as cognitively impaired than the FAB, the latter was more feasible for assessing patients with physical impairment. Simple task modifications proved effective in allowing patients with speech and motor impairments to undergo screening. Future studies are required to validate both measures, establish optimal cut-off scores, and validate modifications. PMID- 24239184 TI - Outcomes after limb sparing resection in primary malignant pelvic tumors. AB - AIM: To evaluate morbidity, oncologic results and functional outcome in patients with malignant tumors of pelvis treated with limb sparing resection. METHODS: Between March 2002 and November 2010, 106 cases of non metastatic malignant pelvic tumors were treated with limb sparing resections of pelvis. Diagnosis included chondrosarcoma (65), Ewing's sarcoma (25), osteogenic sarcoma (10), synovial sarcoma (3) and malignant fibrous histiocytoma, high grade sarcoma, epitheloid hemangiothelioma (1 each). Three patients had intralesional surgery because of erroneous pre-operative diagnosis of benign tumor and were excluded from final analysis. Remaining 103 patients underwent limb sparing resections with intent to achieve tumor free margins. In 1 case, an intraoperative cardiac event lead to the surgery being abandoned. Reconstruction was done in 2 of 38 cases that did not include resection of acetabulum. For 64 resections involving acetabulum various reconstruction modalities were used. RESULTS: Surgical margins were involved in 20 patients. Forty five patients had complications. 91 patients were available for follow up. Follow up of survivors ranged from 24 to 122 months (mean 55 months).Twenty one patients (23%) had local recurrence. Sixty patients are currently alive, 46 being continuously disease free. Overall survival was 67% at 5 years. Patients in whom acetabulum was retained had better function (mean MSTS score 27) compared to patients in whom acetabulum was resected (mean MSTS score 22). CONCLUSIONS: Though complex and challenging, limb sparing surgery in non metastatic malignant tumors is oncologically safe and has better functional outcomes than after an amputation surgery. PMID- 24239186 TI - Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc. AB - The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors. PMID- 24239187 TI - The effect of the skeleton structure of flavanone and flavonoid on interaction with transferrin. AB - Transferrin has been exploited as a potential drug carrier for targeted drug delivery into cancer cells, which express high levels of transferrin receptors. In the present study, we identified specific structural features in flavonoids that were critical for binding to transferrin. Flavanone naringenin and flavonoid apigenin, two flavonoids with characteristic flavonoid core structures were selected for the study of the effects of C2-C3 single bond in the C-ring on transferrin binding. We determined the binding affinities by fluorescence quenching experiments and investigated the binding modes by CD spectra and molecular modeling. Our results demonstrated that naringenin bound transferrin with an affinity almost 100 times higher than that of apigenin attributed to its higher structural flexibility and lower acidity compared with apigenin. Our docking study showed that naringenin had stronger van der Waals interactions with transferrin, which was believed to contribute to its higher binding affinity. We also found that naringenin-binding induced greater increase in the alpha-helix content in transferrin than apigenin, suggesting that transferrin became more compact upon association with naringenin. Our study demonstrated that naringenin was a ligand for transferrin with good affinity. The results reported herein can facilitate the design and development of drugs that bind transferrin with high affinity. PMID- 24239188 TI - Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors. AB - DYRK1B is a kinase over-expressed in certain cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented. PMID- 24239189 TI - Substituted phenyl as a steroid A-ring mimetic: providing agonist activity to a class of arylsulfonamide nonsteroidal glucocorticoid ligands. AB - A class of arylsulfonamide glucocorticoid receptor agonists that contains a substituted phenyl group as a steroid A-ring mimetic is reported. The structural design and SAR that provide the functional switching of a GR antagonist to an agonist is described. A combination of specific hydrogen bonding and lipophilic elements on the A-ring moiety is required to achieve potent GR agonist activity. This study culminated in the identification of compound 23 as a potent GR agonist with selectivity over the PR and MR nuclear hormone receptors. PMID- 24239190 TI - Why do patients with Simple Mechanical Back Pain seek Urgent Care? AB - OBJECTIVE: To explore why patients with simple mechanical back pain seek urgent care. DESIGN: Qualitative Exploratory Inquiry based on the principles of Grounded Theory. SETTING: Urgent Care. METHODS: Data collection by semi-structured interview. PARTICIPANTS: Eleven patients presenting to urgent care (Accident and emergency, Walk-in Centre and Out of hours service) with back pain. RESULTS: The study identified eight key motivators of patients with mechanical back pain seeking urgent care: (1) GP access, (2) Pain, (3) Function, (4) Something being different, (5) Something being wrong, (6) Desire for investigation, (7) Third Party Influence and (8) Repeat visits. CONCLUSION: This study provides some evidence to support the notion that patients are willing to use primary care services for the treatment of Simple Mechanical Back Pain but that access is frequently limited and untimely. The study concludes that inappropriate attendances at urgent care facilities are frequently a human response to perception of pain severity which is reinforced by functional loss, uncertainty, the need to provide care for others and the encouragement of others. While it is asserted that there is a clear need for mass education in this area, it is also speculated that attendance at urgent care may occur to overtly escalate the need for assistance and illustrate to sceptical significant others the severity of the condition. PMID- 24239191 TI - Stroke survivors' experiences of somatosensory impairment after stroke: An Interpretative Phenomenological Analysis. AB - BACKGROUND: Somatosensory ability is commonly impaired after stroke. Despite the growing recognition for the need to understand service users' experiences and perspectives in health services provision, the experiences of stroke survivors' living with somatosensory impairment have yet to be reported. OBJECTIVE: To gain an insight into how stroke survivors experience somatosensory impairment after stroke. DESIGN: A qualitative study design was used with data analysed using Interpretative Phenomenological Analysis. METHODS: Semi-structured in-depth interviews were carried out with purposively selected community dwelling stroke survivors who had somatosensory impairment. RESULTS: Five stroke survivors were interviewed in this study. Data analysis resulted in the emergence of three superordinate themes (i) making sense of somatosensory impairment, (ii) interplay of somatosensory impairment and motor control for executing tasks and (iii) perseverance versus learned non-use. The stroke survivors in this study were aware that their somatosensory ability was affected as a result of their stroke, but had difficulty in articulating their experiences of sensation and the impact of the impairment on functional ability. Most often somatosensory impairment was described in terms of difficulties with executing specific tasks, particularly by the upper limb. CONCLUSION: It is important to be aware that somatosensory impairment is of concern to stroke survivors. Further research is needed to develop evidence-based and practice-appropriate clinical assessment tools and treatment strategies for somatosensory rehabilitation after stroke. PMID- 24239192 TI - Inhibition of crystallization caused by Proteus mirabilis during the development of infectious urolithiasis by various phenolic substances. AB - Infectious urolithiasis is a consequence of persistent urinary tract infections caused by urease producing bacteria e.g. Proteus mirabilis. These stones are composed of struvite and carbonate apatite. Their rapid growth and high recurrence indicate that so far appropriate methods of treatment have not been found. In the present study, the inhibitory effect of phenolic compounds was investigated in vitro against formation of struvite/apatite crystals. The impact of these substances with different chemical structures on crystallization caused by clinical isolates of P. mirabilis was tested spectrophotometrically using a microdilution method. Among the 11 tested compounds resveratrol, epigallocatechin gallate, peralgonidin, vanillic and coffee acids at the concentrations 250-1000 MUg/ml inhibited P. mirabilis urease activity and crystallization. However, only vanillic acid had such an effect on all tested strains of P. mirabilis. Therefore, using an in vitro model, bacterial growth, crystallization, urease activity and pH were examined for 24h in synthetic urine with vanillic acid. Effect of vanillic acid was compared with that of other known struvite/apatite crystallization inhibitors (acetohydroxamic acid, pyrophosphate) and it was shown that vanillic acid strongly inhibited bacterial growth and the formation of crystals. It can be assumed that this compound, after further studies, can be used in the treatment or prophylaxis of infectious urolithiasis. PMID- 24239193 TI - Selected phenotypic features of BR91, a unique spirochaetal strain isolated from the Culex pipiens mosquito. AB - Growth temperature range, resistance to selective antibiotics, activities of 23 enzymes, protein fingerprints and fatty acids composition of the spirochaetal strain BR91, isolated from the Culex pipiens mosquito, were tested. The spirochaetes were grown in BSK-H Complete liquid medium. The optimal in vitro growth temperature of the strain was 33 degrees C. Strain BR91 was sensitive to trimethoprim, nalidixic acid, 5-fluorouracil, and tolerated phosphomycin. The strain produced acid and alkaline phosphatase, esterase (C4), esterase-lipase (C8), leucine arylamidase, naphthol-AS-BI-phosphohydrolase and alpha-fucosidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) assay revealed several major proteins in the size range of 13-16 kDa, 22-30 kDa and 37 131 kDa. Fatty acid methyl ester (FAME) analysis showed that C14:0, C16:0, C18:1 omega9c and summed feature 5 (C18:2 omega6,9c and/or C18:0 anteiso) are major fatty acids. This study highlights certain phenotypic differences between strain BR91 and the Lyme disease spirochaete Borrelia burgdorferi, and supports the hypothesis that strain BR91 represents a unique taxonomical entity in a system of spirochaetal species. PMID- 24239194 TI - Current status of the use of inferior vena cava filters in cases of pulmonary embolism in CCUs: From the Tokyo CCU Network. AB - OBJECTIVE: To elucidate the current status of use of inferior vena cava filters (IVCFs) in cases of pulmonary embolism at institutions belonging to the Tokyo CCU Network. METHODS: We conducted a retrospective investigation of 832 consecutive cases of pulmonary embolism reported on survey forms to the Tokyo CCU Network between 2005 and 2010. RESULTS: Of 832 cases of pulmonary embolism, IVCFs were used in 338 (40.6%) and not used in 415 (49.9%). Their use was unclear in 79 (9.5%) cases. The use rate gradually increased each year from 2005 until 2008 but decreased from 2009 onward. Moreover, 68.9% of the IVCFs used in cases were non permanent types. In terms of pulmonary embolism severity, the rate of use was 37.2% in non-massive cases, 49.4% in sub-massive cases, 46.9% in massive cases, and 31.9% in collapse cases. Thirty-day mortality in cases of collapse in which IVCFs were not used was extremely high at 75.8%, suggesting that in many cases, rapid deterioration may occur with insufficient time for IVCF insertion. The differences in IVCF usage rate among institutions were large in the range of 12.5 90% from 2005 to 2008, which slightly declined to the range of 25.0-72.2% from 2009 to 2010. CONCLUSIONS: We elucidated the current IVCF use status in cases of pulmonary embolism at institutions belonging to the Tokyo CCU Network. Since the status of use differed among institutions, future studies of effective methods of use are required. PMID- 24239195 TI - Forced diuresis with the RenalGuard system: impact on contrast induced acute kidney injury. AB - Kidney injury following the administration of iodinated contrast media occurs particularly in patients with reduced kidney and cardiac function and when large doses of contrast are used. There is little compelling evidence that vasodilators and anti-oxidants prevent this injury. Most prevention trials have employed intravenous volume loading as a central strategy. However, the success of this approach depends upon maintaining euvolemia while producing a vigorous diuresis. A novel strategy for maintaining euvolemia and inducing a vigorous diuresis has been developed using the RenalGuard system. In this review; the mechanism of protective action is reviewed. The trials of the RenalGuard device are reviewed and future uses of the device are discussed. PMID- 24239197 TI - Pregnancy-associated intracranial hemorrhage: results of a survey of neurosurgical institutes across Japan. AB - BACKGROUND: Pregnancy-associated hemorrhagic stroke is considered a serious complication. Although coagulopathy, pregnancy-induced hypertension, eclampsia, and other systemic complications have been emphasized, pre-existing cerebrovascular diseases (CVDs) have not been fully analyzed. To clarify the role of these vascular lesions more in detail, the Japan Neurosurgical Society conducted a nationwide survey on all the neurosurgical institutes across Japan. METHODS: This 2-year survey focused on hemorrhagic stroke occurring in pregnancy, delivery, and puerperium. Clinical data based on retrospective chart review were obtained through a questionnaire and analyzed according to the time of onset, underlying CVDs, obstetric systemic complications, therapeutic approaches, and maternal and neonatal prognoses. RESULTS: The survey identified 97 hemorrhagic strokes that were associated with pregnancy. Baseline CVDs responsible for hemorrhage were detected in 54 cases (55.7%), among which 47 lesions (87.0%) had been undiagnosed before stroke onset. The detection rate of baseline CVDs before the 32nd week of gestation was significantly higher than that after the 32nd week (90.0% versus 53.3%, P = .0017). Arteriovenous malformations (AVMs) were the most frequent CVDs causing intracranial hemorrhage, occurring at 1.8 times the frequency of ruptured aneurysms during pregnancy. Poor outcomes, including 10 deaths, were seen in 36.1% of the cases despite aggressive treatment. CONCLUSION: Pregnancy-associated hemorrhagic strokes frequently concealed baseline CVDs, especially when they occurred before the 32nd week of gestation. AVMs were the predominant bleeding source. For appropriate treatment, therefore, close examination for cerebral vascular lesions is essential when a pregnancy associated hemorrhagic stroke is encountered. PMID- 24239196 TI - Searching for salvageable brain: the detection of ischemic penumbra using various imaging modalities? AB - Various imaging modalities are used to identify the ischemic penumbra in patients with acute ischemic stroke. Although single-photon emission computed tomography (CT), perfusion-weighted magnetic resonance imaging (MRI), and perfusion CT are used to evaluate residual cerebral blood flow in the ischemic area, validation of the perfusion threshold for the penumbra has not been established. The ischemic core corresponds generally to areas with early ischemic changes, such as parenchymal hypoattenuation on CT, restricted apparent diffusion coefficient on diffusion-weighted MRI, or very low cerebral blood volume on perfusion CT. A mismatch of these abnormalities is thought to correspond to the ischemic penumbra and has been used in clinical trials. Although new ligands, such as (18)F fluoromisonidazole, that bind to hypoxic but viable ischemic tissue are currently available, positron emission tomography has yet to be developed as a clinical tool. PMID- 24239198 TI - Expression profile of shelterin components in plasma cell disorders. Clinical significance of POT1 overexpression. AB - The core complex of telomere-associated proteins, named the shelterin complex, plays a critical role in telomere protection and telomere length (TL) homeostasis. In this study, we have explored changes in the expression of telomere-associated genes POT1, TIN2, RAP1 and TPP1, in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). A total of 154 patients: 70 with MGUS and 84 with MM were studied. Real-time quantitative PCR was used to quantify gene expression. TL was evaluated by Terminal Restriction Fragments. Our data showed increased expression of POT1, TPP1, TIN2 and RAP1 in MM with respect to MGUS patients, with significant differences for POT1 gene (p=0.002). In MM, the correlation of gene expression profiles with clinical characteristics highlighted POT1 for its significant association with advanced clinical stages, high calcium and beta2-microglobulin levels (p=0.02) and bone lesions (p=0.009). In multivariate analysis, POT1 expression (p=0.04) was a significant independent prognostic factor for overall survival as well as the staging system (ISS) (p<0.02). Our findings suggest for the first time the participation of POT1 in the transformation process from MGUS to MM, and provide evidence of this gene as a useful prognostic factor in MM as well as a possible molecular target to design new therapeutic strategies. PMID- 24239199 TI - The anatomic- and clinical-based NERS (new risk stratification) score II to predict clinical outcomes after stenting unprotected left main coronary artery disease: results from a multicenter, prospective, registry study. AB - OBJECTIVES: The present study aimed to establish a risk score using a simple calculation with an enhanced predictive value for major adverse cardiac events (MACE) in patients with unprotected left main coronary artery (UPLMCA) disease after the implantation of a drug-eluting stent (DES). BACKGROUND: The anatomic-, clinical-, and procedure-based NERS (New Risk Stratification) score was superior to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score in predicting MACE after stenting UPLMCA. The complexity of the calculation was its major limitation. METHODS: The NERS score II was derived from our previous 2 studies and externally compared with the NERS and SYNTAX scores in 1,463 patients with UPLMCA disease who underwent implantation of a DES in a prospective, multicenter registry trial. The primary endpoint was MACE at 1 year after the index procedure, including myocardial infarction, cardiac death, and target vessel revascularization. RESULTS: The NERS score II system consisted of 16 (7 clinical and 9 angiographic) variables. A NERS score II >=19 demonstrated enhanced MACE sensitivity and specificity of 84.0% and 76.0% (MACE as the state variable), respectively, which were similar to the NERS score but significantly higher compared with the SYNTAX score. A NERS score II >=19 was the only independent predictor of cumulative MACE (hazard ratio: 3.27; 95% confidence interval [CI]: 1.86 to 5.23; p <= 0.001) and stent thrombosis (odds ratio: 22.15; 95% CI: 12.47 to 57.92; p <= 0.001) at follow-up. CONCLUSIONS: The NERS score II, similar to the conventional NERS score, is more predictive of MACE than the SYNTAX score in UPLMCA patients after implantation of a DES. PMID- 24239200 TI - Drug interactions with good old clopidogrel: case closed. PMID- 24239201 TI - Concomitant administration of clopidogrel with statins or calcium-channel blockers: insights from the TRITON-TIMI 38 (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel thrombolysis in myocardial infarction 38). AB - OBJECTIVES: This study sought to evaluate the clinical relevance of potential clopidogrel drug-drug interactions. BACKGROUND: Some studies have demonstrated that statins and calcium-channel blockers (CCBs) may attenuate the pharmacodynamic effects of clopidogrel. METHODS: The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38) enrolled 13,608 patients with an acute coronary syndrome (ACS) and planned percutaneous coronary intervention (PCI), and randomized them to clopidogrel or prasugrel. Use of a statin or CCB was left to the discretion of the treating physician. A multivariable Cox model with propensity score was employed to evaluate the association between statin or CCB use and clinical outcomes. RESULTS: Of the 6,795 subjects assigned to clopidogrel, 4,794 (70.6%) were on a CYP3A4-metabolized statin, and 966 (14.2%) were on a CCB at randomization. The risk of cardiovascular (CV) death, myocardial infarction (MI), or stroke was similar regardless of baseline use of statins (adjusted hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 0.85 to 1.22) or CCBs (adjusted HR: 1.16; 95% CI: 0.94 to 1.43) in clopidogrel-treated patients. Further, the combined use of a CCB and atorvastatin 80 mg daily (adjusted HR: 0.82; 95% CI: 0.37 to 1.84), or a CCB, statin, and proton pump inhibitor (adjusted HR: 1.04; 95% CI: 0.70 to 1.54) were not associated with an increased risk of CV death, MI, or stroke. The use of statins or CCBs did not modify the relative efficacy of prasugrel versus clopidogrel for the primary endpoint (p for interaction = 0.43, 0.55, respectively). CONCLUSIONS: In patients with ACS undergoing PCI, the use of statins or CCBs was not associated with an increased risk of CV events in clopidogrel-treated patients. Consistent results were observed when the drugs were administered alone, together, or in combination with proton pump inhibitors. PMID- 24239202 TI - 5-year results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions). AB - OBJECTIVES: This study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease. BACKGROUND: The use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up. METHODS: SPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis. RESULTS: Five-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p = 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time. CONCLUSIONS: At 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up. PMID- 24239203 TI - Drug-eluting balloon in peripheral intervention for the superficial femoral artery: the DEBATE-SFA randomized trial (drug eluting balloon in peripheral intervention for the superficial femoral artery). AB - OBJECTIVES: This study sought to compare paclitaxel-eluting balloon (PEB) with conventional percutaneous transluminal angioplasty (PTA), followed by systematic implantation of a self-expanding nitinol bare-metal stent (BMS) in patients at risk for restenosis. BACKGROUND: PTA is an effective strategy for treating atherosclerosis of the femoropopliteal axis (FPA). Whereas PEB have shown advantage over uncoated balloons in the treatment of simple lesions, it is unknown whether these results are applicable to complex degrees of FPA atheroma. METHODS: A total of 104 patients (110 FPA lesions in 110 limbs) were randomly assigned to either PEB + BMS or PTA + BMS. The primary endpoint was 12-month binary restenosis. Secondary endpoints were freedom from target lesion revascularization and major amputation. Post hoc subanalyses were performed for the comparison of long (>=100 mm) versus short lesions and true lumen versus subintimal approach. RESULTS: Mean lesion length was 94 +/- 60 versus 96 +/- 69 mm in the PEB + BMS and PTA + BMS groups (p = 0.8), respectively. The primary endpoint occurred in 9 (17%) versus 26 (47.3%) of lesions in the PEB + BMS and PTA + BMS groups (p = 0.008), respectively. A near-significant (p = 0.07) 1-year freedom from target lesion revascularization advantage was observed in the PEB + BMS group. No major amputation occurred. No significant difference was observed according to lesion characteristics or technical approach. CONCLUSIONS: Pre dilation with PEB angioplasty prior to BMS implantation, as compared to PTA + BMS in complex FPA lesions, reduces restenosis and target lesion revascularization at 12-month follow-up. Restenosis reduction is maintained irrespective of lesion length and recanalization technique. (Drug Eluting Balloon in Peripheral Intervention for the Superficial Femoral Artery [DEBATE-SFA]; NCT01556542). PMID- 24239204 TI - [Trueperella bernardiae soft tissue infection and bacteremia]. PMID- 24239205 TI - Supercluster takes a walk on the wild side. AB - In a recent Proc. Natl. Acad. Sci. USA paper by Wiemann et al., a gene supercluster for secondary metabolite production in Aspergillus fumigatus is genetically dissected. The analysis demonstrates that gene regulation takes place at different layers and that genes belonging to specific clusters are intertwined. PMID- 24239206 TI - Biomarker for high-risk patients with stage II colon cancer. PMID- 24239207 TI - Treatment of HER2-positive breast cancer: looking backwards briefly. PMID- 24239208 TI - Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. AB - BACKGROUND: Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. METHOD: Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. FINDINGS: Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR 103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77.3-94.4) for the low-risk group, and 60% (46.3-71.0) for the high-risk group (hazard ratio [HR] 4.24, 95% CI 2.13-8.47; p<0.0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74.3-91.8) for the low-risk group, and 57% (42.8-68.5) for the high-risk group (HR 3.63, 1.86-7.01; p<0.0001), and in the independent validation set of patients, was 85% (79.6-89.0) for the low-risk group and 54% (46.4-61.1) for the high-risk group (HR 3.70, 2.56-5.35; p<0.0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1.69, 1.17-2.45; p=0.0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. CONCLUSION: Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. FUNDING: Natural Science Foundation of China. PMID- 24239209 TI - Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta analysis. AB - BACKGROUND: Novel endoscopic technologies could allow optical diagnosis and resection of colonic polyps without histopathological testing. Our aim was to establish the sensitivity, specificity, and real-time negative predictive value of three types of narrowed spectrum endoscopy (narrow-band imaging [NBI], image enhanced endoscopy [i-scan], and Fujinon intelligent chromoendoscopy [FICE]), confocal laser endomicroscopy (CLE), and autofluorescence imaging for differentiation between neoplastic and non-neoplastic colonic lesions. METHODS: We identified relevant studies through a search of Medline, Embase, PubMed, and the Cochrane Library. Clinical trials and observational studies were eligible for inclusion when the diagnostic performance of NBI, i-scan, FICE, autofluorescence imaging, or CLE had been assessed for differentiation, with histopathology as the reference standard, and for which a 2 * 2 contingency table of lesion diagnosis could be constructed. We did a random-effects bivariate meta-analysis using a non linear mixed model approach to calculate summary estimates of sensitivity and specificity, and plotted estimates in a summary receiver-operating characteristic curve. FINDINGS: We included 91 studies in our analysis: 56 were of NBI, ten of i scan, 14 of FICE, 11 of CLE, and 11 of autofluorescence imaging (more than one of the investigated modalities assessed in eight studies). For NBI, overall sensitivity was 91.0% (95% CI 88.6-93.0), specificity 85.6% (81.3-89.0), and real time negative predictive value 82.5% (75.4-87.9). For i-scan, overall sensitivity was 89.3% (83.3-93.3), specificity 88.2% (80.3-93.2), and real-time negative predictive value 86.5% (78.0-92.1). For FICE, overall sensitivity was 91.8% (87.1 94.9), specificity 83.5% (77.2-88.3), and real-time negative predictive value 83.7% (77.5-88.4). For autofluorescence imaging, overall sensitivity was 86.7% (79.5-91.6), specificity 65.9% (50.9-78.2), and real-time negative predictive value 81.5% (54.0-94.3). For CLE, overall sensitivity was 93.3% (88.4-96.2), specificity 89.9% (81.8-94.6), and real-time negative predictive value 94.8% (86.6-98.1). INTERPRETATION: All endoscopic imaging techniques other than autofluorescence imaging could be used by appropriately trained endoscopists to make a reliable optical diagnosis for colonic lesions in daily practice. Further research should be focused on whether training could help to improve negative predictive values. FUNDING: None. PMID- 24239211 TI - Endoscopic optical biopsy: when we look, what can we see? PMID- 24239210 TI - Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. AB - BACKGROUND: Neoadjuvant chemotherapy with trastuzumab for patients with HER2 positive breast cancer can produce a pathological complete response in the breast in 30-65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. METHODS: This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. FINDINGS: From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56.5%, 95% CI 47.8-64.9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54.2%, 95% CI 45.7-62.6) who received concurrent treatment (difference 2.3%, 95% CI -9.3 to 13.9). No treatment-related deaths occurred. The most common severe toxic effects were neutropenia (35 [25.3%] of 138 patients in the sequential group vs 45 [31.7%] of 142 patients in the concurrent group) and fatigue (six [4.3%] vs 12 [8.5%]). Left ventricular ejection fraction dropped below the institutional lower limit of normal at week 12 in one (0.8%) of 130 patients who received sequential treatment and four (2.9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7.1%) of 126 patients and in six (4.6%) of 130 patients, respectively. INTERPRETATION: Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted. FUNDING: US National Cancer Institute. PMID- 24239212 TI - Disease control through fertility control: Secondary benefits of animal birth control in Indian street dogs. AB - We sought to (1) survey sexually intact street dogs for a wide range of diseases in three cities in Rajasthan, India and (2) evaluate links between the health of non-treated dogs and both the presence and duration of animal birth control (ABC) programs. ABC regimes sterilize and vaccinate stray dogs in an attempt to control their population and the spread of rabies. They are commonly suggested to improve the health of those dogs they serve, but here we provide evidence that these benefits also extend to untreated dogs in the community. Viral and bacterial disease seroprevalences were assessed in 240 sexually intact street dogs from Jaipur, Jodhpur, and Sawai Madhopur cities in October and September 2011. Those individuals and 50 additional dogs were assessed for the presence of ticks, fleas, fight wounds, and given body condition scores. Dogs in cities with an ABC program had with significantly (p<0.05) higher overall body condition scores, lower prevalence of open wounds likely caused by fighting, flea infestations, infectious canine hepatitis, Ehrlichia canis, Leptospira interrogans serovars, and canine distemper virus antibodies. However, those same dogs in cities with ABC programs had significantly higher prevalence of Brown Dog Tick (Rhipicephalus sanguineus) infestations. Canine parvovirus and Brucella canis prevalences were not significantly different between cities. This study is the first to demonstrate the health benefits of ABC on non-vaccinated diseases and non-treated individuals. PMID- 24239213 TI - Pharmacist, general practitioner and consumer use of written medicine information in Australia: are they on the same page? AB - BACKGROUND: Providing written medicine information to consumers enables them to make informed decisions about their medicines, playing an important role in educating and improving health literacy. In Australia, standardized written medicine information called Consumer Medicine Information (CMI) is available for medicines as package inserts, computer prints, or leaflets. Consumers want and read CMI, but may not always ask for it. General practitioners (GPs) and pharmacists are an important source of written medicine information, yet may not always provide CMI in their practice. OBJECTIVE: To examine and compare the awareness, use and provision of CMI by consumers, pharmacists and general practitioners (GPs). METHODS: Based on previous studies, structured questionnaires were developed and administered to a national sample of consumers (phone survey); community pharmacists and GPs (postal surveys) about utilization of CMI. Descriptive, comparative and logistic regression analyses were conducted. RESULTS: The respondents comprised of 349 pharmacists, 181 GPs and 1000 consumers. Two-thirds of consumers, nearly all (99%) pharmacists and 90% of GPs were aware of CMI. About 88% of consumers reported receiving CMI as a package insert, however most pharmacists (99%) and GPs (56%) reported providing computer generated CMI. GPs' and pharmacists' main reason for providing CMI was on patient request. Reasons for not providing were predominantly because consumers were already taking the medicine, concerns regarding difficulty understanding the information, or potential non-adherence. Of the 691 consumers reportedly reading CMI, 35% indicated concerns after reading. Factors associated with reading included gender, type of CMI received and frequency of provision. CONCLUSION: Consumers want and read information about their medicines, especially when received from their GP or pharmacist. Healthcare professionals report usually discussing CMI when providing it to patients, although continued improvements in dissemination rates are desirable. Regular use of CMI remains a challenge, and ongoing strategies to promote CMI use are necessary to improve uptake of CMI in Australia. PMID- 24239214 TI - [Pseudo-ptosis after bi-canaliculo-nasal intubation]. PMID- 24239215 TI - [Diagnosis and treatment of dysthyroid orbitopathy: a multidisciplinary disease]. AB - Graves' disease is a common autoimmune disorder that can be complicated, especially in smokers, by an orbitopathy which can sometimes jeopardize vision and result in functional sequelae affecting quality of life of these patients. Although the diagnosis of dysthyroid orbitopathy is usually obvious, clinical evaluation must specify the stage of progression (clinical activity score) and severity according to the European Group EUGOGO classification. At first, rapid restoration of the euthyroid state, smoking cessation and simple symptomatic ophthalmic treatment are suggested. In the case of severe or active orbitopathy, oral or intravenous corticosteroid therapy with or without orbital radiation therapy (and even emergency orbital surgery in the case of compressive optic neuropathy) should be implemented. Ultimately, orbital surgery (orbital decompression in cases of exophthalmos), oculomotor surgery (diplopia) or eyelid surgery (retraction) may be required depending on the severity of sequelae. A multidisciplinary approach involving ophthalmologist, endocrinologist and orbital surgeon should facilitate an overall diagnosis and treatment plan for these patients. PMID- 24239216 TI - [Removal of lateral orbital wall for management of orbital cavernous hemangioma]. AB - INTRODUCTION: A relatively rare condition, cavernous hemangioma of the orbit poses a problem due to difficulty of the surgical approach. Modifications in surgical approaches and better understanding of these tumors preoperatively allow for less disfiguring elective surgery than before. MATERIALS AND METHODS: Five cases of orbital cavernous hemangiomas reviewed in our department between 2005 and 2009 underwent surgery by external lateral approach with removal of the lateral orbital wall. RESULTS: Resection of the tumor was complete in all cases, with one case of capsular rupture. Short- and long-term morphologic and aesthetic results were satisfactory in all patients. CONCLUSION: The external lateral approach with removal of the lateral orbital wall is a safe technique that allows good exposure of the tumor, facilitating its removal. PMID- 24239217 TI - [Degenerative lesions of the peripheral retina]. AB - Degenerative lesions of the peripheral retina are present from teenage years onwards and increase with age. These abnormabilities are frequent, some of them being benign while others predispose to retinal tears and detachment. In the latter case, the lesions are rhegmatogenous and may justify prophylactic treatment by laser photocoagulation. We distinguish congenital lesions of the peripheral retina and intraretinal, chorioretinal and vitreoretinal degenerations. The holes and tears observed in 2% of the population consist of round atrophic holes, "horseshoe" tears, oral dialyses and giant tears. PMID- 24239218 TI - [Pediatric orbital cellulitis without sinusitis: report of four cases]. AB - INTRODUCTION: Pediatric orbital cellulitis is most often caused by ethmoid sinusitis. We present a description of 4 atypical cases of orbital cellulitis without sinusitis. PATIENTS AND METHODS: A 4-day-old girl presented with medical canthal swelling and preseptal cellulitis caused by bilateral congenital dacryocystoceles. The second patient was an 8-year-old boy seen for infectious conjunctivitis complicated by preseptal cellulitis without sinusitis. Conjunctival cultures revealed Neisseria gonorrheae. The next patient, a 5-month old boy, presented with lid swelling, fever, proptosis and epiphora. It was caused by dacryocystitis extending into the ethmoid and complicated by a sub periostal abscess with mass effect on the globe. The fourth patient was a 10-year old boy referred for inflammatory eyelid edema and severe non-axial proptosis. Imaging revealed an orbital tumor; the diagnosis of rhabdomyosarcoma was confirmed by anatomopathology. DISCUSSION: Thorough etiologic work-up of orbital cellulitis in children will prevent missing a non-sinus-based cause such as lacrimal infections, conjunctivitis secondary to atypical pathogens, or even tumors. All patients should undergo a detailed clinical examination, orbital imaging and microbiological testing. CONCLUSION: Orbital cellulitis in children poses diagnostic and therapeutic difficulties due to the many possible etiologies. Aside from sinusitis, the most important etiologies to pursue are lacrimal system infections and tumors. When confronted with a non-specific clinical presentation, thorough etiologic work-up is essential, in view of the potential life-threatening, functional and social implications. PMID- 24239219 TI - Can we improve ABVD in Hodgkin's lymphoma? PMID- 24239220 TI - Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. AB - BACKGROUND: Roughly 70-80% of patients with advanced stage Hodgkin's lymphoma are cured with various first-line and second-line treatments, including ABVD, BEACOPP, and stem-cell transplantation. Brentuximab vedotin has shown significant clinical activity, with a manageable safety profile, in patients with relapsed or refractory Hodgkin's lymphoma. We aimed to assess the safety and early clinical efficacy of this drug as first-line treatment in combination with standard or modified-standard treatment in patients with previously untreated Hodgkin's lymphoma. METHODS: We did a phase 1, open-label, dose-escalation safety study comparing brentuximab vedotin in combination with standard (ABVD) or a modified standard (AVD) treatment. Patients were enrolled into the groups sequentially. Main entry criteria were newly diagnosed, treatment-naive, CD30-positive patients with Hodgkin's lymphoma who had histologically confirmed stage IIA bulky disease or stage IIB-IV disease and an Eastern Cooperative Oncology Group performance status of two or less. Patients received doses of 0.6, 0.9, or 1.2 mg/kg brentuximab vedotin by intravenous infusion every 2 weeks with either ABVD (25 mg/m(2) doxorubicin, 10 units/m(2) bleomycin, 6 mg/m(2) vinblastine, and 375 mg/m(2) dacarbazine) or AVD (ABVD modified regimen without the inclusion of bleomycin) for up to six cycles. Our primary objectives were to assess the safety profile and establish the maximum tolerated dose (MTD) of brentuximab vedotin in combination with ABVD and AVD. The safety profile and MTD was assessed for the safety population. The study has completed and the final analysis is presented. This study was registered with ClinicalTrials.gov, number NCT01060904. FINDINGS: Between Jan 29, 2010, and Sept 17, 2012, 51 patients were enrolled and received at least one dose of brentuximab vedotin. The maximum tolerated dose of brentuximab vedotin when combined with ABVD or AVD was not exceeded at 1.2 mg/kg. 21 (95%) of 22 patients given brentuximab vedotin and ABVD achieved complete remission, as did 24 (96%) of 25 patients given brentuximab vedotin and AVD. Adverse events were generally grade 1 or 2; however, an unacceptable number of patients in the brentuximab vedotin and ABVD groups had pulmonary toxic effects (11 [44%] of 25), which exceeded the historical incidence for ABVD alone. No patients experienced pulmonary toxic effects when treated with brentuximab vedotin plus AVD. The most common grade 3 or worse events were neutropenia (20 [80%] of 25 patients in the brentuximab vedotin and ABVD group vs 20 [77%] of 26 patients in the brentuximab vedotin and AVD group), anaemia (five [20%] vs three [12%]), febrile neutropenia (five [20%] vs two [8%]), pulmonary toxic effects (six [24%] vs 0), syncope (three [12%] vs two [8%]), dyspnoea (three [12%] vs one [4%]), pulmonary embolism (three [12%] vs 0), fatigue (one [4%] each), and leucopenia (one [4%] each). Serious events occured in 41% of all patients (14 [56%] in the brentuximab vedotin and ABVD group and seven [27%] in the brentuximab vedotin and AVD group). Serious events occurring in 10% of patients or more overall were febrile neutropenia (four [16%] in the brentuximab vedotin and ABVD group vs two [8%] in the brentuximab vedotin and AVD group), and, in the brentuximab vedotin and ABVD group only, pulmonary toxic effects (six [24%]). INTERPRETATION: Brentuximab vedotin should not be given with bleomycin in general or specifically as first-line therapy for patients with treatment naive, advanced stage Hodgkin's lymphoma. 1.2 mg/kg brentuximab vedotin combined with AVD given every 2 weeks was generally well tolerated by patients. At present, a phase 3 trial comparing brentuximab vedotin plus AVD to ABVD alone is ongoing (ClinicalTrials.gov, number NCT01712490) and will formally assess whether brentuximab vedotin plus AVD might redefine therapy in treatment-naive patients with Hodgkin's lymphoma. FUNDING: Seattle Genetics Inc and Takeda Pharmaceuticals International Co. PMID- 24239221 TI - Tuberculosis or tularemia? A molecular study in cervical lymphadenitis. AB - BACKGROUND: Over the last two to three decades there has been a marked decrease in certain bacterial infections in Turkey. One of them is tuberculosis. Of note, statistics published by the Turkish Ministry of Health (MoH) show decreasing pulmonary tuberculosis (PTB), but on the other hand, increasing extrapulmonary tuberculosis (EPTB). The most common form of EPTB is tuberculous cervical lymphadenitis (TCL). The increase in the number of TCL cases despite the decline in cases of PTB is seen as a paradoxical issue. In contrast there has been an increase in the number of oropharyngeal tularemia cases in the last decade in Turkey. The aim of this study was to draw attention to the importance of differentiating between TCL and tularemia lymphadenitis, because these diseases may have a similar histopathological appearance. METHODS: Thirty-two cases diagnosed as TCL were identified from the archives of a pathology laboratory (Patomer Pathology Laboratory, Bursa, Turkey). PCR tests for Francisella tularensis and Mycobacterium tuberculosis were carried out on the paraffin tissue blocks of these cases. At the same time, statistical data on PTB and EPTB for the period 1996-2010 were retrieved from the MoH and reviewed. Statistics related to tularemia, which has been diagnosed since 1988 and has been increasing in the last 10 years, were obtained from the Department of Zoonoses of the MoH. RESULTS: Six out of 32 (19%) cases who had previously been diagnosed with 'casseifying granulomatous lymphadenitis consistent with tuberculosis' were found to be positive for tularemia by PCR test of the cervical lymph nodes. CONCLUSIONS: Oropharyngeal tularemia should be kept in mind in the differential diagnosis of cervical lymphadenitis in widespread geographic regions of the Northern Hemisphere, including the Asian continent. In particular, if granulomatous inflammation with necrosis is seen histopathologically, tularemia should be excluded before making the diagnosis of TCL. PMID- 24239222 TI - Does war contribute to family violence against children? Findings from a two generational multi-informant study in Northern Uganda. AB - After 20 years of civil war in Northern Uganda, the continuity of violence within the family constitutes a major challenge to children's healthy development in the post-conflict era. Previous exposure to trauma and ongoing psychopathology in guardians potentially contribute to parental perpetration against children and dysfunctional interactions in the child's family ecology that increase children's risk of maltreatment. In order to investigate distal and proximal risk factors of child victimization, we first aimed to identify factors leading to more self reported perpetration in guardians. Second, we examined factors in the child's family environment that promote child-reported experiences of maltreatment. Using a two-generational design we interviewed 368 children, 365 female guardians, and 304 male guardians from seven war-affected rural communities in Northern Uganda on the basis of standardized questionnaires. We found that the strongest predictors of self-reported aggressive parenting behaviors toward the child were guardians' own experiences of childhood maltreatment, followed by female guardians' victimization experiences in their intimate relationship and male guardians' posttrautmatic stress disorder (PTSD) symptoms and alcohol-related problems. Regarding children's self-report of victimization in the family, proximal factors including violence between adults in the household and male guardians' PTSD symptom severity level predicted higher levels of maltreatment. Distal variables such as female guardians' history of childhood victimization and female guardians' exposure to traumatic war events also increased children's report of maltreatment. The current findings suggest that in the context of organized violence, an intergenerational cycle of violence persists that is exacerbated by female guardians' re-victimization experiences and male guardians' psychopathological symptoms. PMID- 24239223 TI - A novel dental implant abutment with micro-motion capability--development and biomechanical evaluations. AB - OBJECTIVE: The aim of this study was to develop a novel dental implant abutment with a micro-motion mechanism that imitates the biomechanical behavior of the periodontal ligament, with the goal of increasing the long-term survival rate of dental implants. METHODS: Computer-aided design software was used to design a novel dental implant abutment with an internal resilient component with a micro motion capability. The feasibility of the novel system was investigated via finite element analysis. Then, a prototype of the novel dental implant abutment was fabricated, and the mechanical behavior was evaluated. RESULTS: The results of the mechanical tests and finite element analysis confirmed that the novel dental implant abutment possessed the anticipated micro-motion capability. Furthermore, the nonlinear force-displacement behavior apparent in this micro motion mechanism imitated the movement of a human tooth. The slope of the force displacement curve of the novel abutment was approximately 38.5 N/mm before the 0.02-mm displacement and approximately 430 N/mm after the 0.03-mm displacement. SIGNIFICANCE: The novel dental implant abutment with a micro-motion mechanism actually imitated the biomechanical behavior of a natural tooth and provided resilient function, sealing, a non-separation mechanism, and ease-of-use. PMID- 24239224 TI - Classification of stilbenoid compounds by entropy of artificial intelligence. AB - A set of 66 stilbenoid compounds is classified into a system of periodic properties by using a procedure based on artificial intelligence, information entropy theory. Eight characteristics in hierarchical order are used to classify structurally the stilbenoids. The former five features mark the group or column while the latter three are used to indicate the row or period in the table of periodic classification. Those stilbenoids in the same group are suggested to present similar properties. Furthermore, compounds also in the same period will show maximum resemblance. In this report, the stilbenoids in the table are related to experimental data of bioactivity and antioxidant properties available in the technical literature. It should be noted that stilbenoids with glycoxyl groups esterified with benzoic acid derivatives, in the group g11000 in the extreme right of the periodic table, show the greatest antioxidant activity as confirmed by experiments in the bibliography. Moreover, the second group from the right (g10111) contains E-piceatannol, which antioxidant activity is recognized in the literature. The experiments confirm our results of the periodic classification. PMID- 24239225 TI - SeXX matters in immunity. AB - The significant contributions of sex to an immune response, specifically in the context of the sex bias observed in susceptibility to infectious and autoimmune diseases and their pathogenesis, have until recently, largely been ignored and understudied. This review highlights recent findings related to sex-specific factors that provide new insights into how sex determines the transcriptome, the microbiome, and the consequent immune cell functional profile to define an immune response. Unquestionably, accumulating data confirm that sex matters and must be a consideration when decisions around therapeutic intervention strategies are developed. PMID- 24239226 TI - De novo cavernoma developing from an asymptomatic thalamic microhemorrhage. AB - Cavernomas are low-flow vascular lesions affecting approximately 0.5% of the population. Historically these have been considered congenital lesions, but numerous reports have demonstrated de novo formation. The phenomenon is well documented in patients with the familial disease form and after cranial radiotherapy, but outside of these circumstances there is scant evidence as to the potential etiology. The authors present a 5 year MRI series of a 56-year-old woman with no known risk factors demonstrating cavernoma formation and growth from previously normal brain. The patient was consistently asymptomatic during follow-up. Given the history and imaging findings, we propose that cavernomas can arise directly from angiogenic proliferation secondary to microhemorrhage from unrelated causes. PMID- 24239227 TI - The role of fibroblast growth factor receptor 4 polymorphisms in the susceptibility and clinical features of ischemic stroke. AB - Some polymorphisms in the fibroblast growth factor receptor 4 gene (FGFR-4) have been correlated with coronary artery disease, however, the role of polymorphisms in the FGFR-4 gene in ischemic stroke remain unknown. A total of 270 patients with ischemic stroke and 297 controls were recruited. Stroke subtype was classified and clinical severity of stroke in patients was evaluated. The polymorphisms in the FGFR-4 were genotyped. There were no significant differences of genotype distributions and allele frequencies of rs145302848C/G and rs147603016G/A between stroke patients and controls (all p>0.05). However, genotype frequencies and allele frequencies at rs351855G/A (Gly388Arg) were significantly different between stroke patients and controls (both p<0.001). With the rs351855GG genotype as a reference, the presence of rs351855AA homozygote had a significantly increased risk for stroke (adjusted odds ratio 2.663; 95% confidence interval 1.673-4.229, p<0.001). The polymorphisms at rs145302848C/G and rs147603016G/A did not influence the susceptibility of stroke in this study. All FGFR-4 polymorphisms were not associated with clinical features such as Trial of Org 10172 in Acute Stroke Treatment subtype or stroke severity as indicated by mean National Institutes of Health Stroke Scale scores. Our study suggests a positive association between FGFR-4 gene polymorphism at rs351855G/A and susceptibility to ischemic stroke. PMID- 24239228 TI - Protein-protein interaction network analysis and gene set enrichment analysis in epilepsy patients with brain cancer. AB - Many patients with brain cancer experience seizures or epilepsy and tumor associated epilepsy (TAE) significantly decreases their quality of life. This study aimed to achieve a better understanding of the mechanisms of TAE. The differentially expressed genes (DEG) between epilepsy patients with or without brain tumor were firstly screened using the Linear Models for Microarray Data package using GSE4290 datasets from the USA National Center for Biotechnology Information Gene Expression Omnibus database. Then the protein-protein interaction (PPI) network, using data from the Human Protein Reference Database and the Biological General Repository for Interaction Datasets, was constructed. For further analysis, the PPI network structure and clusters in this PPI network were identified by ClusterOne. Meanwhile, gene set enrichment analysis was performed to illuminate the biological pathways and processes which generally affect patients with TAE. A total of 5113 DEG were identified and a PPI network, which contained 114 DEG and 21 normal genes, was established. Proteins, which mainly belonged to the mini chromosome maintenance and collagen families, were discovered to be enriched in the three identified clusters in the PPI network. Finally, several biological pathways (including cell cycle, DNA replication and transforming growth factor beta1 signaling pathways) and processes (such as nucleocytoplasmic transport, nuclear transport and regulation of phosphorylation) were identified. Proteins in these three clusters may become new targets for TAE treatment. Our results provide some potential underlying biomarkers for understanding the pathogenesis of epilepsy in patients with brain tumor. PMID- 24239229 TI - Intracranial pseudolymphoma presenting with grand mal seizures. AB - Primary central nervous system lymphoproliferative disorders comprise a heterogenous group of intracranial disease, predominantly of the high-grade non Hodgkin's lymphoma type. We report a 56-year-old woman who developed new-onset grand mal seizures and was found to have two small uniformly enhancing dural based lesions, which were radiologically concerning for meningiomas. Biopsy demonstrated findings consistent with benign, reactive lymphoid tissue. The patient's seizures resolved post-operatively. To our knowledge, this is the first reported patient with intracranial pseudolymphoma presenting as grand mal seizures. This case highlights this rare differential consideration in a patient with symptomatic dural-based lesion. PMID- 24239230 TI - Aluminium in human sweat. AB - It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329MUg/L. These data equate to a daily excretion of between 234 and 7192MUg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. PMID- 24239231 TI - The Meryon Society Lecture at the 38th Oxford Muscle Symposium, June 28th 2013: the story of the distal myopathies. PMID- 24239233 TI - Efficacy of immunomodulation in the treatment of profound thrombocytopenia after adult cardiac surgery. AB - OBJECTIVE: Causes of profound thrombocytopenia (platelet count <60 K) developing days after cardiac surgery include heparin platelet factor 4 antibodies, thrombotic thrombocytopenic purpura-like antibodies, and endotoxin generated by pulmonary infections. Modulation of immune-mediated profound thrombocytopenia with intravenous immunoglobulin could be efficacious for any of these conditions. METHODS: From 2002 to 2010, profound thrombocytopenia developed in 20 consecutive patients within days after cardiac surgery; 19 patients underwent valve or aortic operations, and 1 patient underwent coronary bypass. Risk profiles were high preoperatively: Patients' mean age was 73 years, 50% underwent nonelective procedures, 100% had comorbidities, and 25% underwent reoperations. When decreasing platelet counts approached 60 K, intravenous immunoglobulin was started at 1.5 g/kg intravenously over 5 days. Anticoagulation and platelet transfusions were avoided. In 1 patient, profound thrombocytopenia failed to reverse promptly, and daily plasmapheresis was introduced. Platelet counts before and after interventions were assessed with linear regression analyses over time, including a spline function and statistical knot coincident with starting intravenous immunoglobulin. RESULTS: In 19 of 20 patients, profound thrombocytopenia stabilized and rebounded within 2 to 4 days after initiating intravenous immunoglobulin. In the remaining slow-responding patient, addition of plasmapheresis was associated with rapid recovery. In every patient, coincident multiorgan failure reversed, and 19 of 20 patients recovered uneventfully and survived hospitalization with no limb ischemia or tissue loss. No complications of intravenous immunoglobulin therapy or plasmapheresis were observed. CONCLUSIONS: Although mechanisms of profound thrombocytopenia after cardiac surgery are poorly understood, they likely relate to inappropriate autoimmune moieties causing peripheral platelet aggregation and multiorgan failure. A protocol involving immunomodulation with intravenous immunoglobulin supplemented by plasmapheresis appeared safe and efficacious. Direct immunologic interventions for profound thrombocytopenia could improve postoperative outcomes. PMID- 24239235 TI - BRCA1 shields vascular smooth muscle cells from oxidative stress. AB - BACKGROUND: Excessive production of reactive oxygen species (ROS), in part via upregulation of DNA damage pathways, is a central mechanism governing pathologic activation of vascular smooth muscle cells (VSMCs). We hypothesized that the breast cancer 1, early onset (BRCA1) gene that is involved in cellular resistance to DNA damage limits ROS production and oxidative stress in VSMCs. METHODS: We evaluated basal and H2O2-stimulated expression of BRCA1 in human aortic smooth muscle cells (HASMCs). In vitro gain-of-function experiments were performed in BRCA1 adenovirus (Ad-BRCA1)-transfected HASMCs. ROS production and expression of Nox1 and its key regulatory subunit p47phox, key components of the ROS-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, were evaluated. In vivo gain-of-function experiments were performed in spontaneously hypertensive (SHR) rats treated with Ad-BRCA1 (5 * 10(10) IU/rat). Blood pressure, vascular ROS generation, Nox1, and p47phox expression were measured. RESULTS: BRCA1 was constitutively expressed in murine, rat, and human smooth muscle cells (SMCs). H2O2 significantly reduced BRCA1 expression with a resultant increase in ROS generation. BRCA1-overexpressing HASMCs were protected against H2O2-induced ROS generation, in part, via downregulation of the ROS-producing NADPH oxidase subunits Nox1 and p47phox. Ad-BRCA1 treatment in SHR rats was associated with a sustained increase in aortic BRCA1 expression, lower aortic ROS production, reduced gammaH2A.X levels, greater RAD51 foci, and decreases in blood pressure. CONCLUSIONS: BRCA1 is a novel and previously unrecognized target that may shield VSMCs from oxidative stress by inhibiting NADPH Nox1-dependent ROS production. Gene- and/or cell-based approaches that improve BRCA1 bioavailability may represent a new approach in the treatment of diverse vascular diseases associated with an aberrant VSMC phenotype. PMID- 24239236 TI - Long-term outcome after laparoscopic myotomy for achalasia. AB - OBJECTIVES: Achalasia has a variety of therapeutic options. We sought to determine the long-term outcome of laparoscopic myotomy in a large group of patients. METHODS: We conducted a retrospective record review of 500 patients who underwent laparoscopic myotomy and follow-up with a standardized dysphagia questionnaire. RESULTS: Between April 1998 and June 2011, 276 men and 224 women underwent a laparoscopic myotomy. Their median age was 51 years (range, 8-89 years). Preoperative symptoms included dysphagia in 472 patients (94.4%), regurgitation in 382 patients (76.4%), heartburn in 203 patients (40.6%), chest pain in 168 (33.6%) patients, and weight loss (median, 10 kg) in 264 patients (52.8%). Prior therapy (dilation in 239, botulinum toxin type A in 135, or myotomy in 30) had been performed in 303 patients (60.6%). Preoperative manometry was available in 413 patients (82.6%) and revealed a median lower esophageal sphincter pressure of 31 mm Hg (range, 0-50 mm Hg), absent peristalsis in 97.6%, and no lower esophageal sphincter relaxation in 75.1%. A laparoscopic myotomy with partial fundoplication (Toupet n = 268, Dor n = 209) was done in 477 patients (95.4%) and myotomy only in 23 patients (4.6%). Conversion to open was necessary in 16 patients (3.2%). There were 52 (10.4%) esophageal perforations all repaired during the myotomy-and 26 (5.2%) other complications, including bleeding, atrial fibrillation, and pneumonia. There was no operative mortality. Median length of stay was 2 days (range, 1-20 days). Dysphagia questionnaires were returned by 48.2% of patients (241 out of 500) a median of 77.5 months after myotomy (range, 15-176 months). Eighty patients (32.2%) reported no problems with swallowing at the time of the survey. Of 160 patients who had swallowing problems, 40 patients (22.2%) classified the problem as mild or less, 98 patients classified the problem as moderate (70.0%), and 22 patients classified the problem as severe (15.7%). The question concerning frequency of swallowing problems was answered by 160 patients and occurred once a week or less in 70 patients (43.8%), several times a week in 41 patients (25.6%), and at least daily in 49 patients (30.6%). Analysis of all 241 patients who returned questionnaires revealed that 170 out of 241 (70.5%) reported heartburn, 89 out of 241 (36.9%) reported regurgitation, and 159 out of 241 (66.0%) had taken antacids or histamine 2 blockers or proton pump inhibitors within the past 30 days of the survey. The only factor affecting outcome was age; patients older than age 65 years had a better chance of having no difficulty swallowing at follow-up (P = .0174). Sex, prior therapy, Toupet versus Dor, conversion to open, or esophageal mucosal perforation did not affect long-term swallowing outcome. CONCLUSIONS: Laparoscopic myotomy with partial fundoplication is a safe operation. The long term outcome is extremely effective and approximately one-third of patients have no evidence of persistent symptoms at follow-up. Furthermore, those who have persistent symptoms rarely have severe or very frequent complaints. Patients older than age 65 years tend to have a better outcome. PMID- 24239237 TI - Effects of repetitive freeze-thawing cycles on T2 and T2 of the Achilles tendon. AB - INTRODUCTION: In this study we sought to evaluate the effects of multiple freezing and thawing cycles on two MR parameters to study Achilles tendon, T2 and T2. MATERIALS AND METHODS: Four fresh Achilles tendons were imaged on a 3T clinical scanner and again after 1, 2, 4, and 5 freeze-thaw cycles with spin-echo (SE) and ultrashort echo time (UTE) sequences. Regions of interest were manually drawn over the entire Achilles tendon and mono-exponential curves were used to determine T2 and T2 relaxation times. RESULTS: There was no statistically significant difference in mean T2 or T2 values between the fresh specimens and after subsequent cycles of freeze-thaw treatment (p>0.1). Linear regression between SE T2 values at baseline and after successive freeze-thaw cycles demonstrated moderate agreement (r=0.60) whereas UTE T2 values at baseline and after successive-freeze thaw cycles demonstrated strong agreement (r=0.92). CONCLUSION: These findings suggest that changes between specimens seen in vitro are due to factors other than frozen storage. Furthermore, our results suggest that there is stronger agreement between baseline (fresh) and successive freeze thaw T2 values of tendon obtained with the UTE technique in comparison to T2 values obtained with a conventional clinical CPMG technique. PMID- 24239238 TI - Initial CT-guided needle biopsy of extremity skeletal lesions: diagnostic performance and experience of a tertiary musculoskeletal center. AB - INTRODUCTION: Appendicular long bones are the target for a wide spectrum of bony lesions with variable clinical presentations. Biopsy procedures are needed for subsequent proper patient's management. Most of the available literature globally assessed musculoskeletal biopsies with inclusion of repeat biopsy results. We thought to retrospectively assess the diagnostic performance of initial CT-guided percutaneous core needle biopsy (PCNB) of extremity long bone lesions in a tertiary musculoskeletal referral center. PATIENTS AND METHODS: We retrospectively analyzed the outcome of initial CT-guided PCNB of 49 patients who presented with extremity long bone lesions which were biopsied in our hospital during a 36 months' time period. The diagnostic performance was assessed in terms of diagnostic yield and accuracy. RESULTS: There were 34 males and 15 females with a mean age of 33.69 years (range from 4 to 77 years). The overall diagnostic yield of initial biopsies was 87.75% with a diagnostic accuracy of 82.85% derived from the surgically proven cases. The higher diagnostic yield was recorded with malignancy, presence of extra-osseous soft-tissue component as well as mixed and sclerotic lesions. The pathologies of the non-diagnostic biopsies included large cell lymphoma, giant-cell tumor, langerhans cell histiocytosis, osteoid osteoma and a non-ossifying fibroma. CONCLUSION: Initial CT-guided PCNB in extremities' long bones lesions showed high diagnostic performance in malignant, mixed and/or sclerotic lesions as well as lesions with extra-osseous exophytic tissue growth. Lack of extra-osseous components, benign and lytic lesions all had worse diagnostic performance. PMID- 24239239 TI - Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual energy CT. AB - Laryngeal and hypopharyngeal cancer, in particular T4a disease associated with cartilage invasion and extralaryngeal spread, needs to be evaluated accurately because treatment can impact heavily on a patient's quality of life. Reliable imaging tools are therefore indispensible. CT offers high spatial and temporal resolution and remains the preferred imaging modality. Although cartilage invasion can be diagnosed with acceptable accuracy by applying defined criteria for combinations of erosion, lysis and transmural extralaryngeal spread, iodine enhanced tumors and non-ossified cartilage are sometimes difficult to distinguish. MR offers high contrast resolution for images without motion artifacts, although inflammatory changes in cartilage sometimes resemble cartilage invasion. With dual-energy CT, combined iodine overlay images and weighted average images can be used for evaluation of cartilage invasion, since iodine enhancement is evident in tumor tissue but not in cartilage. Extralaryngeal spread can be evaluated from CT, MR or dual-energy CT images and the routes of tumor spread into the extralaryngeal soft tissue must be considered; (1) via the thyrohyoid membrane along the superior laryngeal neurovascular bundle, (2) via the inferior pharyngeal constrictor muscle, and (3) via the cricothyroid membrane. Radiologists need to understand the advantages and limitations of each imaging modality for staging of laryngeal and hypopharyngeal cancer. PMID- 24239240 TI - Calcification at orifices of aortic arch branches is a reliable and significant marker of stenosis at carotid bifurcation and intracranial arteries. AB - PURPOSE: Simple rating scale for calcification in the cervical arteries and the aortic arch on multi-detector computed tomography angiography (MDCTA) was evaluated its reliability and validity. Additionally, we investigated where is the most representative location for evaluating the calcification risk of carotid bifurcation stenosis and atherosclerotic infarction in the overall cervical arteries covering from the aortic arch to the carotid bifurcation. METHOD: The aortic arch and cervical arteries among 518 patients (292 men, 226 women) were evaluated the extent of calcification using a 4-point grading scale for MDCTA. Reliability, validity and the concomitant risk with vascular stenosis and atherosclerotic infarction were assessed. RESULTS: Calcification was most frequently observed in the aortic arch itself, the orifices from the aortic arch, and the carotid bifurcation. Compared with the bilateral carotid bifurcations, the aortic arch itself had a stronger inter-observer agreement for the calcification score (Fleiss' kappa coefficients; 0.77), but weaker associations with stenosis and atherosclerotic infarction. Calcification at the orifices of the aortic arch branches had a stronger inter-observer agreement (0.74) and enough associations with carotid bifurcation stenosis and intracranial stenosis. In addition, the extensive calcification at the orifices from the aortic arch was significantly associated with atherosclerotic infarction, similar to the calcification at the bilateral carotid bifurcations. CONCLUSIONS: The orifices of the aortic arch branches were the novel representative location of the aortic arch and overall cervical arteries for evaluating the calcification extent. Thus, calcification at the aortic arch should be evaluated with focus on the orifices of 3 main branches. PMID- 24239241 TI - Impact of size of region-of-interest on differentiation of renal cell carcinoma and renal cysts on multi-phase CT: preliminary findings. AB - INTRODUCTION: To assess impact of size of regions-of-interest (ROI) on differentiation of RCC and renal cysts using multi-phase CT, with focus on differentiating papillary RCC (pRCC) and cysts given known hypovascularity of pRCC. METHODS: 99 renal lesions (23 pRCC, 47 clear-cell RCC, 7 chromophobe RCC, 22 cysts) underwent multi-phase CT. Subjective presence of visual enhancement was recorded for each lesion. Whole-lesion (WL) ROIs, and small (<= 5 mm(2)), medium (average size of small and large ROIs), and large (half of lesion diameter) peripherally located partial-lesion (PL) ROIs, were placed on non-contrast and nephrographic phases. Impact of ROI size in separating cysts from all RCC and from pRCC based on increased attenuation between phases was assessed using ROC analysis. RESULTS: Visual enhancement was perceived in 96% of ccRCC, 61% of pRCC, and 9% of cysts. AUCs for separating all RCC and cysts for WL-ROI and small, medium, and large PL-ROIs were 91%, 96%, 91% and 93%, and among lesions without visible enhancement were 60%, 79%, 67% and 67%. AUCs for separating pRCC and cysts for WL-ROI and small, medium, and large PL-ROIs were 78%, 92%, 82% and 84%, and among lesions without visible enhancement were 64%, 88%, 69% and 69%. CONCLUSION: Small PL-ROIs had higher accuracy than WL-ROI or other PL-ROIs in separating RCC from cysts, with greater impact in differentiating pRCC from cysts and differentiating lesions without visible enhancement. Thus, when evaluating renal lesions using multi-phase CT, we suggest placing small peripheral ROIs for highest accuracy in distinguishing renal malignancy and benign cysts. PMID- 24239242 TI - MicroRNA-150 inhibits expression of adiponectin receptor 2 and is a potential therapeutic target in patients with chronic heart failure. AB - BACKGROUND: Adiponectin is an anti-inflammatory adipocytokine believed to be involved in the pathogenesis of chronic heart failure (CHF). We aimed to characterize the expression of adiponectin and its receptors in CHF and to assess the impact of microRNAs on the cardiac adiponectin system. METHODS: Expression of adiponectin and adiponectin receptors (ADIPOR1 and ADIPOR2) was studied by qPCR and immunohistochemistry in myocardial tissues of patients with end-stage CHF and control subjects. MicroRNA binding was evaluated by cloning of an ADIPOR2 3' untranslated-region reporter construct and subsequent transfection experiments. Effects of miRNA transfection were analyzed in cardiomyocyte cell cultures by qPCR and Western blotting. Gene silencing of ADIPOR2 was performed by siRNA transfection, and the effects of hypoxia/serum starvation were analyzed by flow cytometry. RESULTS: Although CHF patients displayed elevated plasma adiponectin levels, myocardial adiponectin expression generally was very low. In CHF, cardiac ADIPOR1 expression increased by >4-fold, whereas the increase in ADIPOR2 was less than 2-fold. Reporter gene assays on constructs containing the ADIPOR2-3' untranslated region suggest that microRNA-150 specifically repressed ADIPOR2 expression. Transfection of cardiomyocytes with premiR-150 precursor molecules resulted in 60% down-regulation of ADIPOR2 mRNA and a significant reduction of ADIPOR2 protein expression. MicroRNA-150 was substantially expressed in both normal and CHF myocardium, with a 1.7-fold higher expression in CHF. Finally, knock-down experiments elucidated a stress-protective role of ADIPOR2 in cardiomyocytes. CONCLUSIONS: MicroRNA-150 counteracts ADIPOR2 up-regulation in CHF and thus may contribute to adiponectin resistance. Targeting microRNA-150 may be a future strategy to restore cardioprotective adiponectin effects. PMID- 24239243 TI - Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: report on late toxicity and outcome. AB - BACKGROUND AND PURPOSE: The addition of chemotherapy to preoperative radiotherapy has been established as the standard of care for patients with cT3-4 rectal cancer. As an alternative strategy, we explored intensity-modulated and image guided radiotherapy (IMRT-IGRT) with a simultaneous integrated boost (SIB) in a prospective phase II study. Here, we report outcome and late toxicity after a median follow-up of 54 months. METHODS AND MATERIALS: A total of 108 patients were treated preoperatively with IMRT-IGRT, delivering a dose of 46 Gy in fractions of 2 Gy. Patients (n=57) displaying an anticipated circumferential resection margin (CRM) of less than 2mm based on magnetic resonance imaging received a SIB to the tumor up to a total dose of 55.2 Gy. RESULTS: The absolute incidence of grade >=3 late gastrointestinal and urinary toxicity was 9% and 4%, respectively, with a 13% rate of any grade >=3 late toxicity. The actuarial 5 year local control (LC), progression-free survival (PFS) and overall survival (OS) were 97%, 57%, and 68%. On multivariate analysis, R1 resection and pN2 disease were associated with significantly impaired OS. CONCLUSIONS: The use of preoperative IMRT-IGRT with a SIB resulted in a high 5-year LC rate and non negligible late toxicity. PMID- 24239244 TI - Underlying illness severity and outcome of nosocomial pneumonia: prospective cohort study in intensive care unit. AB - BACKGROUND: Previous studies have suggested that the final outcome of a patient with nosocomial pneumonia (NP) may depend on the patient's illness severity upon admission to the intensive care unit (ICU). AIM: To investigate the relationship between developing NP during hospitalization in an adult ICU and the risk of death with special focus on illness severity at admission in the unit. METHODS: A prospective cohort study was performed among all patients admitted for at least 24h to the ICU of a university reference hospital in Spain from 2006 to 2009. A stratified univariate study was performed according to the patients' illness severity at admission, estimated using the Acute Physiology And Chronic Health Evaluation (APACHE) II index. To determine whether the NP was independently associated with increased mortality in ICU, a multivariate logistic regression analysis was carried out, adjusting for potential confounders. RESULTS: In all, 4427 patients were studied, of whom 233 acquired NP while admitted. Patients who developed NP had a 2.6 higher risk (95% confidence interval: 2.1-3.0) of dying compared with those who did not develop NP. When stratified by the APACHE II index, the significant association remained at each stratum, although the strength of the association decreased as the value of the index increased. In the multivariate analysis, NP was independently associated with death in the ICU. The interaction between NP and the APACHE II index, with a negative coefficient, was also significant. CONCLUSIONS: Developing NP while admitted to the ICU was independently associated with increased mortality. However, the strength of the association decreased as the severity of patient illness upon admission to the ICU increased, not influencing death of patients with severe APACHE II values. PMID- 24239245 TI - Post-traumatic seizures--a prospective, multicenter, large case study after head injury in China. AB - BACKGROUND: Post-traumatic seizures (PTS) is a well-known sequela of traumatic brain injury (TBI). The risk factors for PTS are still controversial. Studies on PTS in China are rare and no large prospective, multicenter-based studies are available. METHODS: Data were collected from 15 hospitals prospectively using standardized structured questionnaires in Shandong, a province in China with a follow-up of 2 years. RESULTS: A total of 3093 traumatic brain injury patients were validated and entered in this analysis. After 6 months of follow-up, 181 (59.9%) patients were identified as having PTS. The number were 236 (78.1%) and 302 after 1 year and 2 years' follow-up, respectively. The cumulative 24-month rate of PTS is 9.8%. Among these 302 patients, 242 were male (80.1%) and 60 female (19.9%). A marked peak was seen in the young people group aged 15-24 (27.8%). Three factors were identified as significant in the multivariate model of PTS: Frontal-temporal lobar contusion, Linear fracture and Severity of TBI measured by initial Glasgow Coma Scale (GCS). CONCLUSION: This prospective cohort study shows the epidemiologic features and risk factors of PTS in China. Frontal temporal lobar contusion, linear fracture and severity of TBI measured by initial Glasgow Coma Scale (GCS) are risk factors for PTS. It is essential to establish a standard surveillance system for PTS. PMID- 24239246 TI - Bilateral hip arthroscopy under the same anesthetic for patients with symptomatic bilateral femoroacetabular impingement: 1-year outcomes. AB - PURPOSE: The purpose of this study was to investigate whether, in patients with bilateral symptomatic femoroacetabular impingement, bilateral surgery under 1 anesthetic is safe and efficacious and allows a rapid return of function compared with staged procedures. METHODS: Three groups were evaluated: in group 1 both hips were treated simultaneously, in group 2 both hips were treated in a staged fashion, and in group 3 a single hip was addressed. The outcome measures were anesthesia and surgical times; time in the hospital; visual analog scale score for pain on postoperative days 1, 3, 7, and 30; analgesic use; and time until the patient could bike, drive, perform office work, perform gym activities, run, and return to play. Midterm evaluation was performed with the Non-Arthritic Hip Score and Western Ontario and McMaster Universities Osteoarthritis Index score at 6 and 12 months postoperatively. RESULTS: We enrolled 76 patients (122 hips) in this study. There were 42 male and 34 female patients. The mean age was 33 years (range, 14 to 50 years), and the mean body mass index was 24 (range, 18 to 35). Group 1 comprised 26 patients (52 hips, 16 male and 10 female patients). Group 2 comprised 20 patients (40 hips, 13 male and 7 female patients), with a mean time between surgeries of 14.56 weeks. Group 3 comprised 33 patients (30 hips, 13 male and 17 female patients). No preoperative differences were found between the groups. The surgical and anesthesia times in group 1 were significantly longer than those in groups 2 and 3. We found no significant differences in postoperative visual analog scale scores, analgesic use, or length of hospital stay. Group 1 required more time before patients were able to ride a stationary bicycle (14.7 days in group 1, 7.8 days in group 2, and 8.5 days in group 3; P < .05). We found no differences between the groups regarding when patients returned to driving, performing office work, or reporting a normal gait. Each group had significant improvements in the Western Ontario and McMaster Universities Osteoarthritis Index and Non-Arthritic Hip Score at 6 and 12 months compared with preoperatively (P < .05). No significant differences in outcome scores were found in the 3 groups before surgery and at 6 or 12 months after surgery. CONCLUSIONS: Simultaneous femoroacetabular impingement surgery does not lead to higher rates of complications, postoperative pain, analgesic use, or side effects. The return to daily activities is similar to a single-hip procedure with the advantage of a single rehabilitation. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 24239247 TI - An 1H-MRS framework predicts the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers. AB - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (1H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD. METHODS: We studied 75 subjects from the largest multigenerational pedigree in the world (~5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two dimensional 1H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to 1H-MRS data while controlling for age, educational level, and sex. RESULTS: We found that (1) the combination of LPPGM Cho/Cr<0.165 and RPPGM Glx/Cr>1.54 fully excluded carriers; (2) LPPGM Cho/Cr>0.165, RPPGM Glx/Cr<1.54, and left parietal white mater NAA/Cr>1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr>1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%. CONCLUSIONS: Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation. PMID- 24239248 TI - Addition of MHPG to Alzheimer's disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer's disease but not other dementias. AB - BACKGROUND: Overlapping clinical features make it difficult to distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and other dementia types. In this study we aimed to determine whether the combination of cerebrospinal fluid (CSF) biomarkers, amyloid-beta42 (Abeta42), total tau protein (t-tau), and phosphorylated tau protein (p-tau), in combination with 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG), could be useful in discriminating DLB from vascular dementia (VaD) and frontotemporal dementia (FTD), as we previously demonstrated for differentiation of DLB from AD. METHODS: We retrospectively analyzed concentrations of MHPG, Abeta42, t-tau, and p-tau in CSF in patients with DLB, AD, VaD, and FTD. Using previously developed multivariate logistic regression models we assessed the diagnostic value of these CSF parameters. RESULTS: The currently used combination of Abeta42, t-tau, and p-tau yielded a sensitivity of 61.9% and a specificity of 91.7% for the discrimination between DLB and AD, but could not discriminate between DLB and VaD or FTD. The addition of MHPG to Abeta42, t-tau, and p-tau improves the discrimination of DLB from AD, yielding a sensitivity of 65.1% and specificity of 100%, but could not distinguish DLB from other forms of dementia. CONCLUSIONS: Our results confirm in a separate patient cohort that addition of MHPG to Abeta42, t-tau, and p-tau improves the discrimination of DLB from AD but not the differentiation of DLB from VaD or FTD. PMID- 24239249 TI - Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease. AB - BACKGROUND: A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics. METHODS: We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation. RESULTS: All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype. CONCLUSIONS: The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century. PMID- 24239250 TI - Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer's disease. AB - OBJECTIVE: The objective of this study was to assess cerebrospinal fluid (CSF) beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) activity in relation to Alzheimer's disease (AD) and to correlate the enzyme activity with protein markers of APP metabolism and axonal degeneration. METHODS: BACE1 activity and protein concentrations were measured and analyzed in 342 participants of the Alzheimer's Disease Neuroimaging Initiative, including 99 normal control, 75 stable mild cognitive impairment (MCI), 87 progressive MCI, and 79 AD dementia cases. All statistical analyses were Bonferroni corrected for multiple comparisons. RESULTS: No significant differences between controls and any of the three patient groups were detected for BACE1 activity and soluble APPbeta (sAPPbeta) concentrations in CSF. Significant correlations with BACE1 activity were found for CSF APPbeta and total tau in all four groups and for CSF phosphorylated tau181 in all groups but the progressive MCI group. There were no correlations for CSF amyloid beta (Abeta)1-42 or for plasma Abeta1-42 and Abeta1 40. CONCLUSIONS: The consistent correlation between BACE1 activity and sAPPbeta supports their role as biomarkers of target engagement in clinical trials on BACE1 inhibition. PMID- 24239251 TI - Polio and the risk for the European Union. PMID- 24239252 TI - Malaria vaccine technology roadmap. PMID- 24239253 TI - Image management systems. PMID- 24239254 TI - Devices for the endoscopic treatment of hemorrhoids. AB - Multiple endoscopic methods are available to treat symptomatic internal hemorrhoids. Because of its low cost, ease of use, low rate of adverse events, and relative effectiveness, RBL is currently the most widely used technique. PMID- 24239255 TI - ASGE's assessment of competency in endoscopy evaluation tools for colonoscopy and EGD. PMID- 24239257 TI - The variability of standard artificial soils: behaviour, extractability and bioavailability of organic pollutants. AB - Artificial soil is an important standard medium and reference material for soil ecotoxicity bioassays. Recent studies have documented the significant variability of their basic properties among different laboratories. Our study investigated (i) the variability of ten artificial soils from different laboratories by means of the fate, extractability and bioavailability of phenanthrene and lindane, and (ii) the relationships of these results to soil properties and ageing. Soils were spiked with (14)C-phenanthrene and (14)C-lindane, and the total residues, fractions extractable by hydroxypropyl-beta-cyclodextrin, and the fractions of phenanthrene mineralizable by bacteria were determined after 1, 14, 28 and 56 days. Significant temporal changes in total residues and extractable and mineralizable fractions were observed for phenanthrene, resulting in large differences between soils after 56 days. Phenanthrene mineralization by indigenous peat microorganisms was suggested as the main driver of that, outweighing the effects of organic matter. Lindane total residues and extractability displayed much smaller changes over time and smaller differences between soils related to organic matter. Roughly estimated, the variability between the artificial soils was comparable to natural soils. The implications of such variability for the results of toxicity tests and risk assessment decisions should be identified. We also suggested that the sterilization of artificial soils might reduce unwanted variability. PMID- 24239256 TI - Photocatalytic degradation of trichloroethylene in aqueous phase using nano ZNO/Laponite composites. AB - The feasibility of nano-ZnO/Laponite composites (NZLc) as a valid alternative to TiO2 to mineralize trichloroethylene (TCE) without difficulties for recovery of photocatalysts was evaluated. Based on the experimental observations, the removal of TCE using NZLc under UV irradiation was multiple reaction processes (i.e., sorption, photolysis, and photocatalysis). Sorption of TCE was thermodynamically favorable due to the hydrophobic partitioning into crosslinked poly vinyl alcohol, and the adsorption onto high-surface-area mineral surfaces of both ZnO and Laponite. The degradation efficiency of TCE can be significantly improved using NZLc under UV irradiation, indicating that ZnO-mediated heterogeneous photocatalytic degradation occurred. However, the degradation efficiency was found to vary with experimental conditions (e.g., initial concentration of TCE, loading amount of NZLc, the intensity of light and initial solution pH). Although the removal of TCE by NZLc was found to be a complex function of sorption, photolysis, and photocatalysis, the photocatalytic degradation of TCE on the surface of ZnO was critical. Consequently, developed NZLc can be applied as a valid alternative to suspended TiO2 powder, and overcome drawbacks (e.g., filtration and recovery of photocatalysts) in degradation of TCE for various water resources. PMID- 24239258 TI - Tailoring activated carbons for the development of specific adsorbents of gasoline vapors. AB - The specific adsorption of oxygenated and aliphatic gasoline components onto activated carbons (ACs) was studied under static and dynamic conditions. Ethanol and n-octane were selected as target molecules. A highly porous activated carbon (CA) was prepared by means of two processes: carbonization and chemical activation of olive stone residues. Different types of oxygenated groups, identified and quantified by TPD and XPS, were generated on the CA surface using an oxidation treatment with ammonium peroxydisulfate and then selectively removed by thermal treatments, as confirmed by TPD results. Chemical and porous transformations were carefully analyzed throughout these processes and related to their VOC removal performance. The analysis of the adsorption process under static conditions and the thermal desorption of VOCs enabled us to determine the total adsorption capacity and regeneration possibilities. Breakthrough curves obtained for the adsorption process carried out under dynamic conditions provided information about the mass transfer zone in each adsorption bed. While n-octane adsorption is mainly determined by the porosity of activated carbons, ethanol adsorption is related to their surface chemistry, and in particular is enhanced by the presence of carboxylic acid groups. PMID- 24239259 TI - Environmental risk analysis of hazardous material rail transportation. AB - An important aspect of railroad environmental risk management involves tank car transportation of hazardous materials. This paper describes a quantitative, environmental risk analysis of rail transportation of a group of light, non aqueous-phase liquid (LNAPL) chemicals commonly transported by rail in North America. The Hazardous Materials Transportation Environmental Consequence Model (HMTECM) was used in conjunction with a geographic information system (GIS) analysis of environmental characteristics to develop probabilistic estimates of exposure to different spill scenarios along the North American rail network. The risk analysis incorporated the estimated clean-up cost developed using the HMTECM, route-specific probability distributions of soil type and depth to groundwater, annual traffic volume, railcar accident rate, and tank car safety features, to estimate the nationwide annual risk of transporting each product. The annual risk per car-mile (car-km) and per ton-mile (ton-km) was also calculated to enable comparison between chemicals and to provide information on the risk cost associated with shipments of these products. The analysis and the methodology provide a quantitative approach that will enable more effective management of the environmental risk of transporting hazardous materials. PMID- 24239260 TI - Exhaust constituent emission factors of printed circuit board pyrolysis processes and its exhaust control. AB - The printed circuit board (PCB) is an important part of electrical and electronic equipment, and its disposal and the recovery of useful materials from waste PCBs (WPCBs) are key issues for waste electrical and electronic equipment. Waste PCB compositions and their pyrolysis characteristics were analyzed in this study. In addition, the volatile organic compound (VOC) exhaust was controlled by an iron impregnated alumina oxide catalyst. Results indicated that carbon and oxygen were the dominant components (hundreds mg/g) of the raw materials, and other elements such as nitrogen, bromine, and copper were several decades mg/g. Exhaust constituents of CO, H2, CH4, CO2, and NOx, were 60-115, 0.4-4.0, 1.1-10, 30-95, and 0-0.7mg/g, corresponding to temperatures ranging from 200 to 500 degrees C. When the pyrolysis temperature was lower than 300 degrees C, aromatics and paraffins were the major species, contributing 90% of ozone precursor VOCs, and an increase in the pyrolysis temperature corresponded to a decrease in the fraction of aromatic emission factors. Methanol, ethylacetate, acetone, dichloromethane, tetrachloromethane and acrylonitrile were the main species of oxygenated and chlorinated VOCs. The emission factors of some brominated compounds, i.e., bromoform, bromophenol, and dibromophenol, were higher at temperatures over 400 degrees C. When VOC exhaust was flowed through the bed of Fe-impregnated Al2O3, the emission of ozone precursor VOCs could be reduced by 70 80%. PMID- 24239261 TI - Tenax extraction for exploring rate-limiting factors in methyl-beta-cyclodextrin enhanced anaerobic biodegradation of PAHs under denitrifying conditions in a red paddy soil. AB - The effectiveness of anaerobic bioremediation systems for PAH-contaminated soil may be constrained by low contaminants bioaccessibility due to limited aqueous solubility and lack of suitable electron acceptors. Information on what is the rate-limiting factor in bioremediation process is of vital importance in the decision in what measures can be taken to assist the biodegradation efficacy. In the present study, four different microcosms were set to study the effect of methyl-beta-cyclodextrin (MCD) and nitrate addition (N) on PAHs biodegradation under anaerobic conditions in a red paddy soil. Meanwhile, sequential Tenax extraction combined with a first-three-compartment model was employed to evaluate the rate-limiting factors in MCD enhanced anaerobic biodegradation of PAHs. Microcosms with both 1% (w/w) MCD and 20mM N addition produced maximum biodegradation of total PAHs of up to 61.7%. It appears rate-limiting factors vary with microcosms: low activity of degrading microorganisms is the vital rate limiting factor for control and MCD addition treatments (CK and M treatments); and lack of bioaccessible PAHs is the main rate-limiting factor for nitrate addition treatments (N and MN treatments). These results have practical implications for site risk assessment and cleanup strategies. PMID- 24239262 TI - Saddle pressure distributions of three saddles used for Icelandic horses and their effects on ground reaction forces, limb movements and rider positions at walk and tolt. AB - Icelandic horse riding practices aim to place the rider further caudally on the horse's back than in English riding, claiming that a weight shift toward the hindquarters improves the quality of the tolt (e.g. giving the shoulder more freedom to move). This study compared saddle pressure patterns and the effects on limb kinetics and kinematics of three saddles: an Icelandic saddle (S(Icel), lowest point of seat in the hind part of the saddle), a treeless saddle cushion (S(Cush)) and a dressage-style saddle (S(Dres)). Twelve Icelandic horses were ridden with S(Icel), S(Cush) and S(Dres) on an instrumented treadmill at walk and tolt. Saddle pressure, limb forces and kinematics were recorded simultaneously. With S(Cush), pressure was highest under the front part of the saddle, whereas the saddles with trees had more pressure under the hind area. The saddles had no influence on the motion patterns of the limbs. The slight weight shift to the rear with S(Cush) and S(Icel) may be explained by the more caudal position of the rider relative to the horse's back. PMID- 24239263 TI - Does milk yield reflect the level of welfare in dairy herds? AB - Under the assumption that milk yield may be reduced in herds with impaired welfare, the present study aimed at investigating whether milk yield could be used as a reliable indicator of welfare. In 125 commercial French dairy herds, the association between the welfare of the herd (evaluated using the Welfare Quality assessment protocol) and cow milk yield was investigated using linear mixed models. Positive associations were identified between milk yield and low aggressions between cows and good emotional state of the herd but there was a negative association with good health assessed through the occurrence of diseases and injuries. These opposite associations resulted in no association with the overall welfare of the herd. Milk yield should not therefore be used as an indicator of overall welfare. PMID- 24239264 TI - Signaling interplay between transforming growth factor-beta receptor and PI3K/AKT pathways in cancer. AB - The transforming growth factor (TGF)-beta and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways are used in cells to control numerous responses, including proliferation, apoptosis, and migration. TGF-beta is known for its cytostatic effects in premalignant states and its pro-oncogenic activity in advanced cancers. The pro-cell survival response exerted by growth-factor mediated activation of PI3K/AKT has been linked to stimulation of tumor formation. Both TGF-beta receptor and PI3K/AKT pathways were initially modeled as linear signaling conduits. Although early studies suggested that these two pathways might counteract each other in balancing cell survival, emerging evidence has uncovered multiple modes of intricate signal integration and obligate collaboration in driving cancer progression. These new insights provide the rationale for exploring their dual targeting in cancer. PMID- 24239265 TI - Response to Otranto et al.: Lungworms in domestic and wild felids: dilemmas still persisting. PMID- 24239266 TI - Role of sulfur assimilation pathway in cadmium hyperaccumulation by Sedum alfredii Hance. AB - Sedum alfredii Hance is a promising cadmium (Cd) hyperaccumulating plant recently identified in China. However, the physiological and molecular mechanisms underlying Cd accumulation, which differentiate hyperaccumulating ecotype (HE) from non-hyperaccumulating ecotype (NHE) has not been elucidated yet. A hydroponic experiment was conducted to investigate the role of sulfur assimilation pathway in Cd hyperaccumulation by the S. alfredii Hance, by analyzing gene expression pattern in sulfur assimilation pathway and the concentration of some sulfur containing compounds. The results show that, sulfur assimilation pathway was affected by Cd differently in HE and NHE S. alfredii Hance. The gene expression pattern of sulfur assimilation pathway was regulated differently in HE and NHE plants, especially the nicotianamine synthase (NAS). NAS transcript levels in root of HE was 141-fold higher than NHE, while in shoots of HE only 0.31-fold higher than NHE. In HE roots, NAS expression level was maximum 3171-fold higher than shoots, while in NHE plants roots NAS expression level was maximum 45.3-fold higher than shoots. In HE plant roots, sulfur, cysteine and methionine concentrations increased 30%, 46% and 835% respectively, by Cd treatment, but in NHE plants roots, sulfur concentration increased less than 1%, cysteine and methionine concentrations decreased 78.5% and 13.3% respectively, by Cd. Cd exposure increased glutathione levels by 142% in HE but less than 10% in NHE plant roots. PMID- 24239267 TI - Flurochloridone-based herbicides induced genotoxicity effects on Rhinella arenarum tadpoles (Anura: Bufonidae). AB - Acute toxicity and genotoxicity of the flurochloridone (FLC)-containing commercial formulation herbicides Twin Pack Gold((r)) (25 percent a.i.) and Rainbow((r)) (25 percent a.i.) were evaluated on Rhinella arenarum (Anura: Bufonidae) tadpoles exposed under laboratory conditions. Lethal effect was evaluated as end point for lethality, whereas frequency of micronuclei (MN) and single cell gel electrophoresis (SCGE) were employed as end points for genotoxicity. Lethality studies revealed equivalent LC-5096 h values of 2.96 and 2.85 mg/L for Twin Pack Gold((r)) and Rainbow((r)), respectively. Twin Pack Gold((r)) did not induce DNA damage at the chromosomal level, whereas Rainbow((r)) increased the frequency of MN only when the lowest concentration (0.71 mg/L) was used. However, all concentrations of Twin Pack Gold((r)) and Rainbow((r)) increased the frequencies of primary DNA lesions estimated by alkaline SCGE. This study represents the first evidence of the acute toxic and genotoxic effects exerted by two FLC-based commercial formulations, Twin Pack Gold((r)) and Rainbow((r)), on tadpoles of an amphibian species native to Argentina under laboratory conditions. Finally, our findings highlight the importance of minimizing the impacts on nontarget living species exposed to agrochemicals. PMID- 24239268 TI - Effect of agro-industrial waste amendment on Cd uptake in Amaranthus caudatus grown under contaminated soil: an oxidative biomarker response. AB - In the present study phytoavailability of Cd, growth yield, cellular Cd accumulation and oxidative stress responses were studied in leafy vegetable Amaranthus caudatus under soil amendments. The test plant was cultivated in Cd contaminated soil (6 ugCdg(-1) soil) amended with different doses: 0.5, 2, 5 and 10 percent of rice husk (RH), saw dust (SD), farmyard manure (FYM), farmyard in combination with nitrogen, and phosphorus and potassium (FYM+NPK). Phytoavailability of Cd in amended soil and cellular Cd accumulation in edible parts (shoot) of A. caudatus declined maximally with 5 percent dose of each amendment, and decrease in Cd content in tissues was 36, 45, 23 and 14 percent under FYM, FYM+NPK, RH and SD amendments, respectively, over the value recorded in plants grown in Cd contaminated non-amended soil (Cd(+)NA soil). The shoot yield in control plant cultivated in the absence of Cd without amendment (Cd(-)NA soil) was 18.1 +/- 0.98 gfwplant(-1) and it was declined up to 50 percent (9.2 +/ 0.80 gfwplant(-1)) when plants were grown in Cd(+)NA soil. Amendments with 5 percent doses of FYM+NPK and FYM enhanced the yield up to 26.5 +/- 0.57 and 20.5 +/- 1.00 gfwplant(-1), respectively, which may be correlated with better mineral nutrients and organic carbon content in amended soil. RH and SD amendments with similar doses improved in yield up to 16.9 +/- 0.43 and 15.2 +/- 0.45 gfwplant( 1), respectively, however, it was still less than that of control. Further, correlation analysis of growth yield, Cd concentration and oxidative stress under these conditions suggest that with the decrease in cellular Cd concentration following amendment the level of oxidative markers (oxidants: O2(-) and H2O2 and lipid peroxidation: malondialdehyde; MDA) declined as a result of significant enhancement in the activity of enzymatic antioxidants (peroxidase, ascorbate peroxidase, superoxide dismutase, dyhydroascorbe reductase and catalase). Thus, the present technique can efficiently reduce the metal load in food chain and also increase plant yield, hence it could be applied in catchments area of urban cities where metal contamination has become an unavoidable factor. PMID- 24239269 TI - Culture-based versus risk-based screening for the prevention of group B streptococcal disease in newborns: a review of national guidelines. AB - BACKGROUND: Maternal colonisation with group B streptococcus (GBS) is recognised as the most frequent cause of severe early onset infection in newborns. National and international guidelines outline two approaches to the prevention of early onset disease in the neonate: risk based management and antenatal culture-based screening. We undertook an analysis of existing national and international guidelines in relation to GBS in pregnancy using a standardised and validated instrument to highlight the different recommended approaches to care. METHODS: English language guidelines on the screening and management of GBS colonisation in pregnant women and the prevention of early-onset group B streptococcal disease in newborns were sought. RESULTS: Four guidelines met the inclusion criteria, one from the United States of America (USA), the United Kingdom (UK), Canada and New Zealand. All four were appraised as at a high standard in terms of development using the AGREE II tool. Both approaches were recommended in the guidelines with different regions of the world advocating different approaches often based on the same evidence. Guidelines from the USA recommend an antenatal culture-based approach while the UK guidelines recommend risk-based management. CONCLUSION: Based on an AGREE II analysis, the standard of the guidelines was high despite having disparate recommendations. Both approaches to the prevention of early onset GBS infection in neonates are recommended with the split being geographically-based. PMID- 24239270 TI - Root cause analysis of non-infectious transfusion complications and the lessons learnt. AB - BACKGROUND: Transfusion of blood and blood products can be associated with hazards which may be at times fatal. Timely reporting of transfusion reactions is imperative for root cause analysis and their prevention in future. METHODS: We retrospectively reviewed the transfusion reactions at our institution during last seven years. The data was retrieved from our computerized blood bank information system and by reviewing the medical charts of patients. The frequency of adverse effects, implicated products, wrong blood transfusion and its outcome were observed. RESULTS AND CONCLUSIONS: During study period (2006-2012), a total of 393,662 blood or blood products were transfused. There were 458 adverse events with an estimated rate of 1.16 per 1000 blood products administered. During 2011 2012, 121 transfusion reactions were reported of 119,921 transfused units. The most common adverse effects were allergic reactions (70 episodes of 121 or 57.8%) followed by febrile non hemolytic transfusion reactions or FNHTR (43 events of 121 or 35.5%). Transfusion associated dyspnea, circulatory overload and transfusion associated lung injury were less frequent. During the study period, 142,066 red cell units were transfused with nine recognized ABO-mismatch transfusions and two fatalities. The computed incidence of ABO-mismatch transfusion was 1 in 15,785 with a mortality rate of 1 in 71,033 units transfused. Etiology included: errors in final bed side check (n=5), blood bank clerical errors (n=3) and mislabeled tube (n=1). A review of these cases prompted hospital transfusion committee for re-enforcing policies and protocols to minimize accidental ABO incompatible transfusions. We concluded that urticaria and FNHTR are the most frequent transfusion reactions in our setting. ABO mismatched blood transfusions are rare but preventable errors and result mainly from clerical imprecisions. PMID- 24239271 TI - Immediate changes in continuous positive airway pressure after bariatric surgery in obese people with obstructive sleep apnoea. PMID- 24239272 TI - Oscillococcinum(r): Misunderstanding or biased interest? PMID- 24239273 TI - Lobaplatin arrests cell cycle progression, induces apoptosis and alters the proteome in human cervical cancer cell Line CaSki. AB - Cervical cancer is one of the most common gynecologic tumors. There is an upward trend in the incidence. The objective of this research was to explore the effect of lobaplatin on cervical cancer CaSki cells proliferation, cell cycle and apoptosis and analysis of the differential expressed proteins of CaSki cells after exposed to lobaplatin. Our findings have shown that lobaplatin inhibits cell proliferations in human cervical cancer CaSki cells in dose- and time dependent manner. Flow cytometry assay confirmed that lobaplatin affected cervical cancer cell survival by blocking cell cycle progression in S phase and G0/G1 phase and inducing apoptosis in dose- and time-dependent manner. Lobaplatin treatment reduced polypyrimidine tract-binding protein 2, ribose-phosphate pyrophosphokinase, hypothetical protein, terminal uridylyltransferase 7, ubiquitin specific protease 16 and heterogeneous nuclear ribonucleoprotein A2/B1 expression and increase zinc finger protein 91, zinc finger protein, C-X-C motif chemokine 10 precursor, stromal cell protein and laminin subunit alpha-4 expression. Some of the differentially expressed proteins may be associated with antitumor effect of lobaplatin. Lobaplatin showed a good antitumour activity in in vitro models of human cervical cancer cells. These results indicate that lobaplatin could be an effective chemotherapeutic agent in human cervical cancer treatment by inducing apoptosis, cell cycle arrest and changing many kinds of protein molecule expression level. PMID- 24239274 TI - Analysis of rhizobial strains nodulating Phaseolus vulgaris from Hispaniola Island, a geographic bridge between Meso and South America and the first historical link with Europe. AB - Hispaniola Island was the first stopover in the travels of Columbus between America and Spain, and played a crucial role in the exchange of Phaseolus vulgaris seeds and their endosymbionts. The analysis of recA and atpD genes from strains nodulating this legume in coastal and inner regions of Hispaniola Island showed that they were almost identical to those of the American strains CIAT 652, Ch24-10 and CNPAF512, which were initially named as Rhizobium etli and have been recently reclassified into Rhizobium phaseoli after the analysis of their genomes. Therefore, the species R. phaseoli is more abundant in America than previously thought, and since the proposal of the American origin of R. etli was based on the analysis of several strains that are currently known to be R. phaseoli, it can be concluded that both species have an American origin coevolving with their host in its distribution centres. The analysis of the symbiovar phaseoli nodC gene alleles carried by different species isolated in American and European countries suggested a Mesoamerican origin of the alpha allele and an Andean origin of the gamma allele, which is supported by the dominance of this latter allele in Europe where mostly Andean cultivars of common beans have been traditionally cultivated. PMID- 24239275 TI - Duodenum: MDCT of acute conditions. AB - Multidetector computed tomography (MDCT) is the technique of choice for evaluating patients with acute abdominal pain. As the jejunum, ileum, and colon comprise the majority of the gastrointestinal tract, radiologists may potentially neglect the duodenum. However, the duodenum is a complex structure that can be affected by both intraperitoneal and extraperitoneal processes due to its central location and proximity to numerous upper abdominal structures. In this review, the MDCT findings of various congenital, inflammatory, traumatic, infectious, vascular, and miscellaneous conditions that affect the duodenum are discussed. PMID- 24239276 TI - Current cigarette smoking is an independent risk factor for subacute stent thrombosis in acute myocardial infarction patients. AB - BACKGROUND: Acute myocardial infarction (AMI) is prevalent and has serious consequences including re-infarction and death. Cigarette smoking is a coronary risk factor for AMI, although a "smoker's paradox" for AMI has been reported in Western countries. On the other hand, some researchers have reported that smoking is associated with subacute stent thrombosis (SAST) after AMI. However, the occurrence of this condition is not well documented in Japan. The aim of this study was to clarify how prior smoking status may affect prognosis, including SAST, in Japanese patients with AMI. METHODS: A total of 266 consecutive patients with AMI were enrolled retrospectively in the study if they had undergone emergency coronary intervention (bare metal stent) within 24h of symptom onset, and had a 5-10 month follow-up examination. The patients were divided into three groups based on their cigarette smoking status (non-smokers, past smokers, and current smokers). RESULTS: Current smokers were significantly younger than the other two groups, although their levels of low density lipoprotein-cholesterol and triglyceride were significantly higher. White blood cell count and hemoglobin level on admission were also significantly higher in current smokers compared with the other two groups. The incidence of SAST was significantly higher in current smokers than in the other groups, although the occurrence of heart failure after AMI was similar in the three groups. On the other hand, improvement in left ventricular ejection fraction was observed in non-smokers and past smokers, but not in current smokers. Multiple logistic analysis revealed that current smoking was an independent risk factor for SAST (odds ratio 5.4; p<0.05). Current smokers were about five times more likely to have a SAST compared with non-smokers. CONCLUSIONS: These findings indicate that current cigarette smoking predicts SAST after primary percutaneous coronary intervention for AMI in Japanese patients. PMID- 24239277 TI - Polystyrene films as barrier layers for corrosion protection of copper and copper alloys. AB - Dip-coated polystyrene layers of sub-micrometre thickness (85-500nm) have been applied on copper and copper alloys (aluminium brass, copper-nickel 70/30), as well as on stainless steel 304, and produced an effective barrier against corrosion and adhesion of corrosion-relevant microorganisms. According to the dynamic wettability measurements, the coatings exhibited high advancing (103 degrees ), receding (79 degrees ) and equilibrium (87 degrees ) contact angles, low contact angle hysteresis (6 degrees ) and surface free energy (31mJ/m(2)). The corrosion rate of copper-nickel 70/30 alloy samples in 3.5% NaCl was as low as 3.2MUm/a (44% of that of the uncoated samples), and in artificial seawater was only 0.9MUm/a (29% of that of the uncoated samples). Cell adhesion was studied by fluorescence microscopy, using monoculture of Desulfovibrio alaskensis. The coatings not only decreased the corrosion rate but also markedly reduced the number of bacterial cells adhered to the coated surfaces. The PS coating on copper gave the best result, 2*10(3)cells/cm(2) (1% of that of the uncoated control). PMID- 24239278 TI - p27 and BCL2 expression predicts response to chemotherapy in head and neck squamous cell carcinomas. AB - OBJECTIVES: Head and neck squamous cell carcinomas (HNSCCs) are characterized by marked heterogeneity in their biological behavior and response to treatment. Our goal was the identification of biomarkers that can be used to predict response to chemotherapy in these patients. MATERIALS AND METHODS: The expression of EGFR, p53, Cyclin D1, p16, p21, p27, p-AKT, HIF-1alpha, Caspase 3 and BCL2 was analyzed by immunohistochemistry in 41 primary laryngeal/hypopharyngeal squamous cell carcinomas of patients that received induction chemotherapy (cisplatin and 5 fluorouracil) as part of their treatment. RESULTS: Positive expression of p27 and BCL2 had a significant predictive value for chemotherapy response in univariate analysis. The combination of both proteins was not superior in predicting the response to chemotherapy. Furthermore, p27 expression was the only significant predictor of chemotherapy response in multivariate analysis (P=0.015). CONCLUSION: p27 Expression may serve as predictive biomarker of response to induction chemotherapy in HNSCC patients. PMID- 24239279 TI - Associations of oral health items of the Vanderbilt Head and Neck Symptom Survey with a dental health assessment. AB - OBJECTIVES: The Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 oral symptom subscale addresses underreported oral health issues. We report the associations of xerostomia, dental health, dentures and trismus questions with oral examination findings. MATERIALS AND METHODS: Between May 2011 and April 2012, fifty head and neck cancer (HNC) patients treated with chemoradiotherapy completed the 50-item VHNSS survey, an oral health assessment by a dentist, salivary flow, and inter-incisal opening (IIO) measurements. RESULTS: Patient reported "problems with dry mouth" correlated with unstimulated salivary flow ( 0.43, p=0.002). "Cracked teeth" (0.55, p=<0.001) or "difficulty chewing due to teeth" (0.43, p=0.004) correlated with urgent/emergent dental issues identified on clinical exam. Scores of >4 on any dental question identified 83% of patients with urgent or emergent needs. The ROC curve separated routine from urgent/emergent dental issues (0.89, p<0.001). IIO correlated with reported jaw movement "limitations" (-0.43, p=0.002). Small numbers of patients with dentures precluded meaningful analysis of this subsample. CONCLUSIONS: Clinically significant oral health issues pertaining to xerostomia, dental health and trismus may be identified using the oral health subscale of the VHNSS version 2.0. MASCC guidelines should be followed by patients with xerostomia. The observation that a score of >4 is highly predictive of dental issues is important and needs further validation. If confirmed, this would be a useful screening tool for identifying and referring HNC patients for dental care. Patients with trismus should receive physical therapy. PMID- 24239280 TI - Pioglitazone and oral cancer risk in patients with type 2 diabetes. AB - BACKGROUND: Pioglitazone has shown an inhibitory effect on the growth of cell lines derived from human salivary gland and human oral squamous cell carcinoma. However, whether this effect can be applied to patients with type 2 diabetes mellitus who use pioglitazone for glycemic control remains unanswered. METHODS: The reimbursement records of all Taiwanese diabetic patients under treatment with oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance database. The entry date was set at 1 January 2006 and a total of 1,093,391 patients with type 2 diabetes were followed up for oral cancer incidence till the end of 2009. Incidences for ever-users, never-users and subgroups of pioglitazone dose-responsive exposure (using the parameters of time since starting pioglitazone, duration of therapy and cumulative dose) were calculated and hazard ratios estimated by Cox regression. RESULTS: There were 58,238 ever-users and 1,035,153 never-users, with respective numbers of incident oral cancer of 201 (0.35%) and 4168 (0.40%), and respective incidences of 94.26 and 114.24 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) did show a significantly lower risk in unadjusted [0.832 (0.722 0.958)] and age-sex-adjusted [0.866 (0.752-0.998)] models. However, the multivariable-adjusted hazard ratio (95% confidence interval) was not significant: 0.992 (0.857-1.148). Although significant P-trends for the dose response parameters could be observed in some of the unadjusted and age-sex adjusted models, none was significant in the multivariable-adjusted models. CONCLUSIONS: Pioglitazone has a null association with oral cancer after adjustment for potential confounders. PMID- 24239282 TI - Ongoing outbreak of multiple blood-borne infections in injecting drug users in Romania. PMID- 24239281 TI - Identifying environmental health priorities in underserved populations: a study of rural versus urban communities. AB - OBJECTIVES: Understanding and effectively addressing persistent health disparities in minority communities requires a clear picture of members' concerns and priorities. This study was intended to engage residents in urban and rural communities in order to identify environmental health priorities. Specific emphasis was placed on how the communities: defined the term environment; their perceptions of environmental exposures as affecting their health; specific priorities in their communities; and differences in urban versus rural populations. STUDY DESIGN: A community-engaged approach was used to develop and implement focus groups and compare environmental health priorities in urban versus rural communities. METHODS: A total of eight focus groups were conducted: four in rural and four in urban communities. Topics included: defining the term environment; how the environment may affect health; and environmental priorities within their communities, using both open discussion and a predefined list. Data were analysed both qualitatively and quantitatively to identify patterns and trends. RESULTS: There were important areas of overlap in priorities between urban and rural communities; both emphasized the importance of the social environment and shared a concern over air pollution from industrial sources. In contrast, for urban focus groups, abandoned houses and their social and physical sequelae were a high priority while concerns about adequate sewer and water services and road maintenance were high priorities in rural communities. CONCLUSIONS: This study was able to identify environmental health priorities in urban versus rural minority communities. In contrast to some previous risk perception research, the results of this study suggest prioritization of tangible, known risks in everyday life instead of rare, disaster-related events, even in communities that have recently experienced devastating damage from tornadoes. The findings can help inform future efforts to study, understand and effectively address environmental issues, and are particularly relevant to developing effective community-based strategies in vulnerable populations. PMID- 24239283 TI - The genetic overlap between schizophrenia and height. AB - Epidemiological studies suggest that height and schizophrenia risk are inversely correlated. These findings might arise because i) height and schizophrenia share genetic variants and ii) the effects of these shared variants are in opposite direction for the two traits. We use genome wide association data to empirically evaluate these hypotheses. We find that variants which impact on height and risk for schizophrenia are distributed across several genomic regions and the directions of effect vary, some consistent and others inconsistent with the direction expected from the phenotypic data. Moreover, signals that were in and not in accord with the phenotypic data aggregated in distinct biological pathways. PMID- 24239284 TI - The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes. AB - Reprogramming differentiated cells into induced pluripotent stem cells (iPSCs) promotes a broad array of cellular changes. Here we show that the let-7 family of microRNAs acts as an inhibitory influence on the reprogramming process through a regulatory pathway involving prodifferentiation factors, including EGR1. Inhibiting let-7 in human cells promotes reprogramming to a comparable extent to c-MYC when combined with OCT4, SOX2, and KLF4, and persistence of let-7 inhibits reprogramming. Inhibiting let-7 during reprogramming leads to an increase in the level of the let-7 target LIN-41/TRIM71, which in turn promotes reprogramming and is important for overcoming the let-7 barrier to reprogramming. Mechanistic studies revealed that LIN-41 regulates a broad array of differentiation genes, and more specifically, inhibits translation of EGR1 through binding its cognate mRNA. Together our findings outline a let-7-based pathway that counteracts the activity of reprogramming factors through promoting the expression of prodifferentiation genes. PMID- 24239285 TI - Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. AB - Recent studies point to a pivotal role of Polycomb repressive complex 2 (PRC2) in stem cell function and cancer. Loss-of-function approaches targeting individual PRC2 subunits have, however, generated findings that are difficult to reconcile. Here, we prevent assembly of both Ezh1- and Ezh2-containing PRC2 complexes by conditional deletion of Eed, a core subunit, and assess hematopoiesis. We find that deletion of Eed exhausts adult bone marrow hematopoietic stem cells (HSCs), although fetal liver HSCs are produced in normal numbers. Eed-null neonatal HSCs express HSC signature genes but are defective in maintenance and differentiation. Comparative gene expression profiling revealed that neonatal and adult HSCs lacking Eed upregulated gene sets of conflicting pathways. Deletion of Cdkn2a, a PRC2 target gene, in Eed-null mice enhances hematopoietic stem/progenitor cell (HSPC) survival but fails to restore HSC functions. Taken together, our findings define developmental-stage-specific requirements for canonical PRC2 complexes in normal HSC function. PMID- 24239286 TI - Prevalence of and risk factors for substance use among perinatally human immunodeficiency virus-infected and perinatally exposed but uninfected youth. AB - PURPOSE: This study examined risk factors associated with recent substance use (SU) among perinatally human immunodeficiency virus (HIV)-infected (PHIV+) and perinatally exposed, uninfected (PHEU) youth and compared SU lifetime prevalence with the general population of United States (U.S.) adolescents. METHODS: We conducted cross-sectional and longitudinal analyses of 511 PHIV+ and PHEU youth (mean age at study entry, 13.2 years; 51% female; 69% PHIV+; and 72% African American) enrolled in a U.S. multisite prospective cohort study between 2007 and 2009. Substance use data were collected by audio computer-assisted self interview. Youth Risk Behavior Surveillance System and Monitoring the Future data were used to compare SU lifetime prevalence with U.S. samples. RESULTS: Perinatal HIV infection was not a statistically significant risk factor for alcohol or marijuana use. Risk factors for alcohol use among PHIV+ youth included higher severity of emotional and conduct problems and alcohol and marijuana use in the home by the caregiver or others. Risk factors for marijuana use among PHIV+ youth included marijuana use in the home, higher severity of conduct problems, and stressful life events. Similar SU risk factors among PHEU youth included SU in the home and higher severity of conduct and emotional problems. Overall lifetime prevalence of SU by age was similar to that in national surveys. CONCLUSIONS: Although SU lifetime prevalence and risk factors for PHIV+ and PHEU adolescents were similar to national norms, the negative consequences are potentially greater for PHIV+ youth. Prevention efforts should begin before SU initiation and address the family and social environment and youth mental health status. PMID- 24239287 TI - Unique obstacle race injuries at an extreme sports event: a case series. AB - Obstacle course endurance events are becoming more common. Appropriate preparedness for the volume and unique types of injury patterns, as well as the effect on public health these events may cause, has yet to be reported in emergency literature. We describe 5 patients who presented with diverse injuries to illustrate the variety of injuries sustained in this competitive event. In particular, 4 of the patients had a history of contact with electrical discharge, an obstacle distinctive to the Tough Mudder experience. PMID- 24239288 TI - TopBP1 controls BLM protein level to maintain genome stability. AB - Human TopBP1 is a key mediator protein involved in DNA replication checkpoint control. In this study, we report a specific interaction between TopBP1 and Bloom syndrome helicase (BLM) that is phosphorylation and cell-cycle dependent. Interestingly, TopBP1 depletion led to decreased BLM protein level and increased sister chromatid exchange (SCE). Moreover, our data indicated that BLM was ubiquitinated by E3 ligase MIB1 and degraded in G1 cells but was stabilized by TopBP1 in S phase cells. Depletion of MIB1 restored BLM protein level and rescued the elevated SCE phenotype in TopBP1-depleted cells. In addition, cells expressing an undegradable BLM mutant showed radiation sensitivity, probably by triggering end resection and inhibiting the nonhomologous end-joining (NHEJ) pathway in G1 phase. Altogether, these data suggest that, although BLM is downregulated in G1 phase in order to promote NHEJ-mediated DNA repair, it is stabilized by TopBP1 in S phase cells in order to suppress SCE and thereby prevent genomic instability. PMID- 24239290 TI - Autoadaptive ER-associated degradation defines a preemptive unfolded protein response pathway. AB - Folding-defective proteins must be cleared efficiently from the endoplasmic reticulum (ER) to prevent perturbation of the folding environment and to maintain cellular proteostasis. Misfolded proteins engage dislocation machineries (dislocons) built around E3 ubiquitin ligases that promote their transport across the ER membrane, their polyubiquitylation, and their proteasomal degradation. Here, we report on the intrinsic instability of the HRD1 dislocon and the constitutive, rapid turnover of the scaffold protein HERP. We show that HRD1 dislocon integrity relies on the presence of HRD1 clients that interrupt, in a dose-dependent manner, the UBC6e/RNF5/p97/proteasome-controlled relay that controls HERP turnover. We propose that ER-associated degradation (ERAD) deploys autoadaptive regulatory pathways, collectively defined as ERAD tuning, to rapidly adapt degradation activity to misfolded protein load and to preempt the unfolded protein response (UPR) activation. PMID- 24239289 TI - Regulation of gene expression by macrolide-induced ribosomal frameshifting. AB - The expression of many genes is controlled by upstream ORFs (uORFs). Typically, the progression of the ribosome through a regulatory uORF, which depends on the physiological state of the cell, influences the expression of the downstream gene. In the classic mechanism of induction of macrolide resistance genes, antibiotics promote translation arrest within the uORF, and the static ribosome induces a conformational change in mRNA, resulting in the activation of translation of the resistance cistron. We show that ketolide antibiotics, which do not induce ribosome stalling at the uORF of the ermC resistance gene, trigger its expression via a unique mechanism. Ketolides promote frameshifting at the uORF, allowing the translating ribosome to invade the intergenic spacer. The dynamic unfolding of the mRNA structure leads to the activation of resistance. Conceptually similar mechanisms may control other cellular genes. The identified property of ketolides to reduce the fidelity of reading frame maintenance may have medical implications. PMID- 24239291 TI - A bacterial toxin inhibits DNA replication elongation through a direct interaction with the beta sliding clamp. AB - Toxin-antitoxin (TA) systems are ubiquitous on bacterial chromosomes, yet the mechanisms regulating their activity and the molecular targets of toxins remain incompletely defined. Here, we identify SocAB, an atypical TA system in Caulobacter crescentus. Unlike canonical TA systems, the toxin SocB is unstable and constitutively degraded by the protease ClpXP; this degradation requires the antitoxin, SocA, as a proteolytic adaptor. We find that the toxin, SocB, blocks replication elongation through an interaction with the sliding clamp, driving replication fork collapse. Mutations that suppress SocB toxicity map to either the hydrophobic cleft on the clamp that binds DNA polymerase III or a clamp binding motif in SocB. Our findings suggest that SocB disrupts replication by outcompeting other clamp-binding proteins. Collectively, our results expand the diversity of mechanisms employed by TA systems to regulate toxin activity and inhibit bacterial growth, and they suggest that inhibiting clamp function may be a generalizable antibacterial strategy. PMID- 24239292 TI - Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to mesenchymal transition. AB - Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of noncoding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here, we show that the Snail1 transcription factor represses mouse pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial to-mesenchymal transition (EMT), we analyzed the regulation of heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1alpha, is transiently released from heterochromatin foci in a Snail1/LOXL2-dependent manner, concomitantly with a downregulation of major satellite transcription. Moreover, preventing the downregulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through LOXL2, thus creating the favorable transcriptional state necessary for completing EMT. PMID- 24239293 TI - Rrp5 binding at multiple sites coordinates pre-rRNA processing and assembly. AB - In vivo UV crosslinking identified numerous preribosomal RNA (pre-rRNA) binding sites for the large, highly conserved ribosome synthesis factor Rrp5. Intramolecular complementation has shown that the C-terminal domain (CTD) of Rrp5 is required for pre-rRNA cleavage at sites A0-A2 on the pathway of 18S rRNA synthesis, whereas the N-terminal domain (NTD) is required for A3 cleavage on the pathway of 5.8S/25S rRNA synthesis. The CTD was crosslinked to sequences flanking A2 and to the snoRNAs U3, U14, snR30, and snR10, which are required for cleavage at A0-A2. The NTD was crosslinked to sequences flanking A3 and to the RNA component of ribonuclease MRP, which cleaves site A3. Rrp5 could also be directly crosslinked to several large structural proteins and nucleoside triphosphatases. A key role in coordinating preribosomal assembly and processing was confirmed by chromatin spreads. Following depletion of Rrp5, cotranscriptional cleavage was lost and preribosome compaction greatly reduced. PMID- 24239294 TI - Investigation of the actin scavenging system in pre-eclampsia. AB - OBJECTIVES: Cell injury releases actin, the most abundant cell protein. Gelsolin and vitamin D binding protein (VDBP) together depolymerise and clear cell-free actin. Impaired actin clearance is associated with several diseases and correlates with clinical outcome. The actin scavenging system was investigated in pre-eclampsia (PE), a procoagulant and proinflammatory state with placental and vascular damage. STUDY DESIGN: Plasma gelsolin and actin free VDBP (AFVDBP) were measured in PE (early onset <33weeks; late onset >=36weeks), matched normal pregnant (normP) and non-pregnant (nonPr) women, using commercially available ELISAs. Longitudinal samples from normP and women who subsequently developed PE were also analysed. RESULTS: Plasma gelsolin fell during pregnancy (p=0.0002), with a concomitant rise in actin-free VDBP (p<0.001). Gelsolin concentrations were only significantly lower in established PE (p<0.05) when compared to non pregnant controls. CONCLUSIONS: We have shown that the components of the actin clearance system, gelsolin and AFVDBP, are altered in normal pregnancy and further changes occur in established PE, suggesting depleted actin clearance in PE. Whether this is a cause or consequence of PE pathophysiology requires further investigation. PMID- 24239295 TI - Ability of an orally administered lactobacilli preparation to improve the quality of the neovaginal microflora in male to female transsexual women. AB - OBJECTIVE: Lactobacilli have been found in the neovagina of very low numbers of transsexual women. We undertook this study to determine whether an orally administered preparation of four lactobacilli strains exerts some measurable effect on the neovaginal microflora of female transsexuals. STUDY DESIGN: 60 male to female transsexual women with penile linked neovagina were randomised into two groups. Women in the intervention group (n=33) received oral probiotic capsules and women in the control group (n=27) placebo in for 7 days. Swabs of the neovagina were taken before and after the therapy. RESULTS: Comparing the first and second swabs, we observed a significant improvement of the Nugent score in the intervention group 16 (48.5%) vs. low improvement in control group 4 (14.8%) (p<0.006). The neovaginal microflora was significantly enriched with lactobacilli after oral supplementation compared to placebo. In the intervention group, an increase by 10,000+/-600 colony forming units (CFU) of presumptive lactobacilli was observed, compared with an increase by 1600+/-100CFU in the control group (p<0.0001). When measured by real-time PCR (c/ml), lactobacilli increased by 1400+/-100c/ml in the intervention group and 300+/-100c/ml in the control group (p<0.0001). CONCLUSION: There was an improvement of vaginal lactobacilli microflora after of oral supplementation with lactobacilli strains in transsexual women. PMID- 24239296 TI - Robust information gain based fuzzy c-means clustering and classification of carotid artery ultrasound images. AB - In this paper, a robust method is proposed for segmentation of medical images by exploiting the concept of information gain. Medical images contain inherent noise due to imaging equipment, operating environment and patient movement during image acquisition. A robust medical image segmentation technique is thus inevitable for accurate results in subsequent stages. The clustering technique proposed in this work updates fuzzy membership values and cluster centroids based on information gain computed from the local neighborhood of a pixel. The proposed approach is less sensitive to noise and produces homogeneous clustering. Experiments are performed on medical and non-medical images and results are compared with state of the art segmentation approaches. Analysis of visual and quantitative results verifies that the proposed approach outperforms other techniques both on noisy and noise free images. Furthermore, the proposed technique is used to segment a dataset of 300 real carotid artery ultrasound images. A decision system for plaque detection in the carotid artery is then proposed. Intima media thickness (IMT) is measured from the segmented images produced by the proposed approach. A feature vector based on IMT values is constructed for making decision about the presence of plaque in carotid artery using probabilistic neural network (PNN). The proposed decision system detects plaque in carotid artery images with high accuracy. Finally, effect of the proposed segmentation technique has also been investigated on classification of carotid artery ultrasound images. PMID- 24239297 TI - A conceptual definition of quality of life with a left ventricular assist device: results from a qualitative study. AB - OBJECTIVE: To develop a conceptual definition of quality of life (QoL) with a left ventricular assist device (LVAD). BACKGROUND: Conceptual and operational definitions of QoL with an LVAD are lacking. METHODS: A grounded theory method was used. Adult, outpatient LVAD recipients (n = 11) participated twice in individual or paired interviews. RESULTS: A conceptual definition of QoL while living with an LVAD was established as: "Being well enough to do and enjoy day-to day activities that are important to me." Participants described 5 important life domains consistent with QoL literature: physical, emotional, social, cognitive, and spiritual/meaning. However, participants identified unique concerns not addressed by generic or heart failure disease specific measures typically used in the LVAD population. CONCLUSION: Existing generic and heart-failure specific QoL measures are not adequate for understanding QoL among LVAD patients. Cognition and spiritual/meaning domains were significant; these need inclusion for comprehensive QoL assessment in the LVAD population. PMID- 24239298 TI - Responses to noxious stimuli in sedated mechanically ventilated adults. AB - OBJECTIVE: To determine the effect of sedation on physiologic responses and comfort before, during and after a noxious stimulus (endotracheal tube suctioning). METHODS: The sample was a subset of a larger, longitudinal descriptive study, blood for endorphins and saliva for alpha-amylase were obtained before and after suctioning. Heart rate (HR), respiration rate (RR), oxygen saturation (SPO2), and arm and leg actigraphy were continuously recorded. RESULTS: 67 subjects from medical and surgical ICUs were primarily deeply (37%) or mildly sedated (54%) prior to suctioning. Alpha-amylase increased post suctioning (p = 0.04); endorphins did not change (p = 0.58). Neither were modified by sedation. There were no changes in HR, RR or SPO2 post suctioning. Arm (p = 0.007) and leg actigraphy (p = 0.057) changed from baseline and depended on sedation level (p = 0.0005). CONCLUSIONS: While a stress marker did increase during suctioning, only the measure of patient arm movement was significantly affected by sedation level. PMID- 24239299 TI - Implementing selective digestive tract decontamination in the intensive care unit: A qualitative analysis of nurse-identified considerations. AB - OBJECTIVE: To describe factors senior critical care nurses identify as being important to address when introducing selective digestive tract decontamination (SDD) in the clinical setting. BACKGROUND: Critically ill patients are at risk of developing ventilator-associated pneumonia (VAP). SDD is one strategy shown to prevent VAP and possibly improve survival in the critically ill. METHODS: We performed a secondary analysis of qualitative data obtained from 20 interviews. An inductive thematic analysis approach was applied to data obtained from senior critical care nurses during phase two of a multi-methods study. RESULTS: There were four primary considerations identified that should be addressed or considered prior to implementation of SDD. These considerations included education of health care professionals, patient comfort, compatibility of SDD with existing practices, and cost. CONCLUSIONS: Despite a lack of experience with, or knowledge of SDD, nurses were able to articulate factors that may influence its implementation and delivery. Organizations or researchers considering implementation of SDD should include nurses as key members of the implementation team. PMID- 24239300 TI - Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame? AB - Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia. PMID- 24239301 TI - An ectopic approach for engineering a vascularized tracheal substitute. AB - Tissue engineering can provide alternatives to current methods for tracheal reconstruction. Here we describe an approach for ectopic engineering of vascularized trachea based on the implantation of co-cultured scaffolds surrounded by a muscle flap. Poly(L-lactic-co-glycolic acid) (PLGA) or poly(epsilon-caprolactone) (PCL) scaffolds were seeded with chondrocytes, bone marrow stem cells and co-cultured both cells respectively (8 groups), wrapped in a pedicled muscle flap, placed as an ectopic culture on the abdominal wall of rabbits (n = 24), and harvested after two and four weeks. Analysis of the biochemical and mechanical properties demonstrated that the PCL scaffold with co culture cells seeding displayed the optimal chondrogenesis with adequate rigidity to maintain the cylindrical shape and luminal patency. Histological analysis confirmed that cartilage formed in the co-culture groups contained a more homogeneous and higher extracellular matrix content. The luminal surfaces appeared to support adequate epithelialization due to the formation of vascularized capsular tissue. A prefabricated neo-trachea was transferred to the defect as a tracheal replacement and yielded satisfactory results. These encouraging results indicate that our co-culture approach may enable the development of a clinically applicable neo-trachea. PMID- 24239302 TI - Polyion complex micellar nanoparticles for integrated fluorometric detection and bacteria inhibition in aqueous media. AB - The development of portable and inexpensive detection methods can significantly contribute to the prevention of water-borne infectious diseases caused by pathogenic bacteria. Here we designed a nanosystem capable of both bacterial detection and inhibition, where polyion complex (PIC) micelles are constructed from negatively-charged tetraphenylethylene (TPE) sulfonate derivatives, which exhibit the aggregation-induced emission (AIE) feature, and cationic diblock copolymers, poly(ethylene oxide)-b-quaternized poly(2-(dimethylamino)ethyl methacrylate) (PEO-b-PQDMA). Upon contacting with bacteria, the PIC nanosystem disintegrates presumably due to competitive binding of polycation blocks with negatively-charged bacterial surfaces. This process is accompanied by a conspicuous quenching of TPE fluorescence emission, serving as a real-time module for microbial detection. Furthermore, the sharp decrease in CFU is indicative of prominent anti-microbial activities. Thus, PIC micelles possess dual functions of fluorometric detection and inhibition for bacteria in aqueous media. By tuning the charge density of TPE sulfonate derivatives and chain length of cationic PQDMA blocks, optimal performance against Gram-negative Escherichia coli has been achieved with a detection limit of 5.5 * 10(4) CFU/mL and minimum inhibitory concentration (MIC) of 19.7 MUg/mL. Tests against Gram-positive Staphylococcus aureus were also conducted to demonstrate versatility of the nanosystem. PMID- 24239303 TI - Multiple conformational selection and induced fit events take place in allosteric propagation. AB - The fact that we observe a single conformational selection event during binding does not necessarily mean that only a single conformational selection event takes place, even though this is the common assumption. Here we suggest that conformational selection takes place not once in a given binding/allosteric event, but at every step along the allosteric pathway. This view generalizes conformational selection and makes it applicable also to other allosteric events, such as post-translational modifications (PTMs) and photon absorption. Similar to binding, at each step along a propagation pathway, conformational selection is coupled with induced fit which optimizes the interactions. Thus, as in binding, the allosteric effects induced by PTMs and light relate not only to population shift; but to conformational selection as well. Conformational selection and population shift take place conjointly. PMID- 24239304 TI - Inter-rater reliability of the GNRB(r) knee arthrometer. AB - BACKGROUND: In clinical settings, where arthrometers are mainly used by different clinicians, knowing the inter-rater reliability of the instrument is crucial in order for the results from different examiners to be accurately interpreted and limitations fully understood. The aim of this study was to evaluate the inter rater reliability of the GNRB(r) knee arthrometer. METHODS: Knee anterior laxity in both knees was tested in a group of young, uninjured subjects (N=27, 13 females) by two examiners. Knee anterior laxity was calculated at test forces of 134 N and 250 N with values presented for the unstandardised and standardised conditions (relative to patellar stabilisation force). RESULTS: The ICCs ranged from 0.220 to 0.424. CONCLUSIONS: The inter-rater reliability of the GNRB(r) knee arthrometer is low. PMID- 24239305 TI - Emergency room visits and readmissions after pediatric urologic surgery. AB - OBJECTIVE: Reducing readmissions has become a focal point to increase quality of care while reducing costs. We report all-cause unplanned return visits following urologic surgery in children at our institution. MATERIALS AND METHODS: Children undergoing urology procedures with returns within 30 days of surgery were identified. Patient demographics, insurance status, type of surgery, and reason for return were assessed. RESULTS: Four thousand and ninety-seven pediatric urology surgeries were performed at our institution during 2012, with 106 documented unplanned returns (2.59%). Mean time from discharge to return was 5.9 +/- 4.9 days (range, 0.3-24.8 days). Returns were classified by chief complaint, including pain (32), infection (30), volume status (14), bleeding (11), catheter concern (8), and other (11). Circumcision, hypospadias repair, and inguinal/scrotal procedures led to the majority of return visits, accounting for 21.7%, 20.7%, and 18.9% of returns, respectively. Twenty-two returns (20.75%) resulted in hospital readmission and five (4.72%) required a secondary procedure. Overall readmission rate was 0.54%, with a reoperation rate of 0.12%. CONCLUSIONS: The rate of unplanned postoperative returns in the pediatric population undergoing urologic surgery is low, further strengthening the argument that readmission rates in children are not necessarily a productive focal point for financial savings or quality control. PMID- 24239306 TI - Plastic in the Thames: a river runs through it. AB - Although contamination of the marine ecosystems by plastics is becoming recognised as a serious pollution problem, there are few studies that demonstrate the contribution made by freshwater catchments. Over a three month period from September to December 2012, at seven localities in the upper Thames estuary, 8490 submerged plastic items were intercepted in eel fyke nets anchored to the river bed. Whilst there were significant differences in the numbers of items at these locations, the majority were some type of plastic. Additionally in excess of 20% of the litter items were components of sanitary products. The most contaminated sites were in the vicinity of sewage treatment works. While floating litter is visible, this study also demonstrates that a large unseen volume of submerged plastic is flowing into the marine environment. It is therefore important that this sub-surface component is considered when assessing plastic pollution input into the sea. PMID- 24239307 TI - Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments of the Hormuz strait, Persian Gulf. AB - The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in the sediment from the Hormuz strait, Persian Gulf. The sum of 16 PAHs (SigmaPAH) concentrations varied from 72.17 to 277.77 ng g(-1) dry weight, with an average value of 131.20 +/- 59.29 ng g(-1) dry weight. An ecological risk assessment of PAHs, indicated that adverse biological effects caused by acenaphthene and acenaphthylene occasionally may take place in the sediment of Hormuz strait. PAH source identification showed that the PAHs in the sediments come from pyrogenic and mixed origin. Based on classification of pollution levels, sediments from Hormuz strait could be considered as low to moderately polluted with PAHs. PMID- 24239308 TI - Detection of macroalgae blooms by complex SAR imagery. AB - Increased frequency and enhanced damage to the marine environment and to human society caused by green macroalgae blooms demand improved high-resolution early detection methods. Conventional satellite remote sensing methods via spectra radiometers do not work in cloud-covered areas, and therefore cannot meet these demands for operational applications. We present a methodology for green macroalgae bloom detection based on RADARSAT-2 synthetic aperture radar (SAR) images. Green macroalgae patches exhibit different polarimetric characteristics compared to the open ocean surface, in both the amplitude and phase domains of SAR-measured complex radar backscatter returns. In this study, new index factors are defined which have opposite signs in green macroalgae-covered areas, compared to the open water surface. These index factors enable unsupervised detection from SAR images, providing a high-resolution new tool for detection of green macroalgae blooms, which can potentially contribute to a better understanding of the mechanisms related to outbreaks of green macroalgae blooms in coastal areas throughout the world ocean. PMID- 24239309 TI - Baseline concentrations of faecal sterols and assessment of sewage input into different inlets of Admiralty Bay, King George Island, Antarctica. AB - The Antarctic region is one of the best preserved environments in the world. However, human activities such as the input of sewage result in the alteration of this pristine site. We report baseline values of faecal sterols in Admiralty Bay, Antarctica. Four sediment cores were collected during the 2006/2007 austral summer at the Ezcurra (THP and BAR), Mackelar (REF) and Martel (BTP) inlets. Concentrations of faecal sterols (coprostanol+epicoprostanol) were <0.16 MUg g( 1), suggesting no sewage contamination and probable "biogenic" contributions for these compounds. Baseline values, calculated using the mean concentration of faecal sterols in core layers for THP, BAR, REF and BTP, were 0.04 +/- 0.02, 0.03 +/- 0.01, 0.07 +/- 0.01 and 0.04 +/- 0.02 MUg g(-1), respectively. These results established as natural contributions of faecal sterols, suggesting that these markers can be useful indicators of human-derived faecal input and contributing to monitoring programs to prevent anthropogenic impacts. PMID- 24239310 TI - Establishing the thermal threshold of the tropical mussel Perna viridis in the face of global warming. AB - With increasing recognition that maximum oxygen demand is the unifying limit in tolerance, the first line of thermal sensitivity is, as a corollary, due to capacity limitations at a high level of organisational complexity before individual, molecular or membrane functions become disturbed. In this study the tropical mussel Perna viridis were subjected to temperature change of 0.4 degrees C per hour from ambient to 8-36 degrees C. By comparing thermal mortality against biochemical indices (hsp70, gluthathione), physiological indices (glycogen, FRAP, NRRT) and behavioural indices (clearance rate), a hierarchy of thermal tolerance was therein elucidated, ranging from systemic to cellular to molecular levels. Generally, while biochemical indices indicated a stress signal much earlier than the more integrated behavioural indices, failure of the latter (indicating a tolerance limit and transition to pejus state) occurred much earlier than the other indices tending towards thermal extremities at both ends of the thermal spectrum. PMID- 24239311 TI - Fish biological effect monitoring of chemical stressors using a generalized linear model in South Sea, Korea. AB - To evaluate the health status at six different study areas, we used the generalized linear model approach with selected biochemical markers in resident fish from uncontaminated and contaminated sites. We also confirmed the independence between the biochemical indices and the morphometric indices including the hepato-somatic index (HSI), gonado-somatic index (GSI), and condition factor (CF) in fish from the sampling areas. The effect of area on the presence of biotransformation markers (ethoxyresorufin-O-deethylase activity; EROD) was significantly high in Masan Bay. The area with the greatest effect on acetylcholinesterase (AChE) activity was Jindong Bay, while there was no significant effect of GSI, HSI, CF, and sex in the EROD model and HSI, CF and sex in the AChE model. These results clarify that fish from Masan, Gwangyang and Jindong Bay were affected by pollutant stress, and the analysis of sensitive biochemical responses allowed for an improved interpretation of the results. PMID- 24239312 TI - Intramedullary nailing of long bone fractures: sixty years of evolution but what the future holds? PMID- 24239313 TI - Extrahepatic metastases of hepatocellular carcinoma: A spectrum of imaging findings. AB - Hepatocellular carcinoma (HCC) is the most common primary tumour of the liver, responsible for significant morbidity and mortality worldwide. In the Western world, it primarily affects patients with cirrhosis, secondary to hepatitis C virus and alcoholism. In the rest of the world, HCC is closely associated with hepatitis B virus infections. Radiologists play a key role in accurately staging HCC, which has important implications for treatment planning. This pictorial review aims to describe the routes of HCC spread and the most frequent sites of metastases, to recognize extrahepatic HCC findings on computed tomography and magnetic resonance imaging, and to understand the implications of HCC staging on treatment planning. PMID- 24239314 TI - Evaluation of single and comparative intradermal tuberculin tests for tuberculosis eradication in caprine flocks in Castilla y Leon (Spain). AB - Goats can act as reservoirs for tuberculosis (TB) infection. The main etiological agents of TB in goats are Mycobacterium caprae and Mycobacterium bovis and they infect also a wide range of domestic and wild animals and humans. Control programmes based mainly on the application of single and comparative intradermal tuberculin (SIT and SCIT respectively) tests are being implemented in certain regions of Spain with a high density of caprine flocks as Castilla y Leon, including goats with epidemiological relationship with cattle. The aim of this study was to evaluate the performance of the intradermal tests in naturally TB infected caprine flocks from this region. The study was performed using data from 17,450 goats in 54 different flocks that were classified as TB-infected in the control programmes executed in 2010 and 2011. Data from 1237 goats from 7 dairy flocks depopulated after the first intradermal testing were used to estimate the sensitivity (Se) using bacteriology as the gold-standard. Overall Se of the SIT test using the severe interpretation was 43.9% (CI 95%, 40.4-47.4) and decreased to 38.8% (CI 95%, 35.5-42.3) using the standard interpretation. Overall Se of the SCIT test ranged between 21.3% (CI 95%, 17.6-25.4) and 7% (CI 95%, 4.9-9.8) depending of the interpretation criteria. A significant weak positive correlation was found between age and skin fold thickness (Spearman's test p<0.05). Results from this study yielded, in general, low Se values probably due the systematic detection and slaughter of reactors as a consequence of the eradication programme in previous years or the presence of factors that may interfere in the diagnosis. Therefore, these results suggest the necessity of including ancillary diagnostic tools and/or strict interpretation criteria to maximize detection of positive animals in infected settings. PMID- 24239315 TI - Association of lung function measurements and visceral fat in men with metabolic syndrome. AB - BACKGROUND: Several studies have reported a positive relationship between lung function impairment and the metabolic syndrome. This is most usually explained by abdominal adiposity. We hypothesized that the main determinant of the association between lung function impairment and abdominal obesity is the presence of visceral fat. METHODS: The present study is a cross-sectional analysis of 98 non diabetic men aged between 50 and 70 years with the metabolic syndrome. The amount of visceral and subcutaneous adipose tissue was determined by an MRI scan. The association between visceral fat and measures of lung function (FEV1, FVC, exhaled and NO) was assessed using linear regression. RESULTS: 98 participants were included in this analysis. There was a linear inverse association between visceral fat and both FEV1 and FVC. None of the other different fat-related measurements (subcutaneous fat, waist circumference and BMI) or features of the metabolic syndrome were found to be associated with these lung function measurements. CONCLUSION: In non-diabetic subjects with the metabolic syndrome and a lung function that is within the normal range, visceral fat is negatively correlated with FEV1 and FVC. PMID- 24239316 TI - Asthma and allergic rhinitis increase respiratory symptoms in cold weather among young adults. AB - BACKGROUND: The occurrence of cold temperature-related symptoms has not been investigated previously in young adults, although cold weather may provoke severe symptoms leading to activity limitations, and those with pre-existing respiratory conditions may form a susceptible group. We tested the hypothesis that young adults with asthma and allergic rhinitis experience cold-related respiratory symptoms more commonly than young adults in general. METHODS: A population-based study of 1623 subjects 20-27 years old was conducted with a questionnaire inquiring about cold weather-related respiratory symptoms, doctor-diagnosed asthma and rhinitis, and lifestyle and environmental exposures. RESULTS: Current asthma increased the risk of all cold weather-related symptoms (shortness of breath adjusted PR 4.53, 95% confidence interval 2.93-6.99, wheezing 10.70, 5.38 21.29, phlegm production 2.51, 1.37-4.62, cough 3.41, 1.97-5.87 and chest pain 2.53, 0.82-7.79). Allergic rhinitis had additional effect especially on shortness of breath (7.16, 5.30-9.67) and wheezing (13.05, 7.75-22.00), some on phlegm production (3.69, 2.49-5.47), but marginal effect on cough and chest pain. INTERPRETATION: Our study shows that already in young adulthood those with asthma, and especially those with coexisting allergic rhinitis, experience substantially more cold temperature-related respiratory symptoms than healthy young adults. Hence, young adults with a respiratory disease form a susceptible group that needs special care and guidance for coping with cold weather. PMID- 24239317 TI - Intestinal disorders caused by scurvy. PMID- 24239318 TI - Altered quality of life in the early stages of chronic hepatitis C is due to the virus itself. AB - Health-related quality of life (HRQOL) is impaired in chronic viral hepatitis and a direct role of the virus, although suggested, has not been demonstrated. Our aim was to evaluate HRQOL at blood donation before knowledge of the diagnosis of both hepatitis C virus (HCV) and hepatitis B virus (HBV) so as to elucidate this matter. METHODS: Prospectively, 67 sequential patients, 35 with HCV and 32 with HBV, and 67 matched controls were administered the generic Short Form-36 (SF-36) questionnaire. After knowledge of diagnosis, the SF-36 was repeated and a disease specific questionnaire (Liver Disease Quality of Life, LDQOL-1.0) was also administered. The Wilcoxon test and Mann-Whitney U were used for between-group comparisons. RESULTS: Before knowledge of diagnosis, patients with HCV had worse HRQOL than controls, with statistically significant changes in 7/8 domains of the SF-36, and also in its physical and mental components. In the HBV group, only 2/8 domains and the physical component were significantly different from controls. After diagnosis, similar changes persisted in the HCV group, whereas two more domains were compromised in the HBV group. Comparisons between the HCV and HBV groups did not show significant differences. CONCLUSION: The finding of greater HRQOL impairment in the HCV group before diagnosis confirms the theory that the presence of HCV in the early stage of the disease is associated with worse quality of life. PMID- 24239319 TI - Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis. AB - AIM: Liver fibrosis is a reversible wound-healing response that occurs following liver injury. In this study, we aimed to investigate the possible protective effects of L-carnitine, N-acetylcysteine and genistein in liver fibrosis induced by carbon tetrachloride (CCl4). In addition, the effects of these agents were compared in the same study. METHODS: In this study, rats were randomly allocated into 8 groups, consisting of 10 rats each, as follows: a control group, CCl4, L carnitine, N-acetylcysteine, genistein, CCl4 and L-carnitine, CCl4 and N acetylcysteine, and CCl4 and genistein. At the end of 6 weeks, blood and liver tissue specimens were collected. Alanine aminotransferase (ALT); aspartate aminotransferase (AST); complete blood count, tumor necrosis factor-alpha (TNF alpha); platelet-derived growth factor-BB (PDGF-BB); interleukin-6 (IL-6); liver glutathione level; oxidant/antioxidant status; scores of hepatic steatosis, necrosis, inflammation, and fibrosis; and the expression of alpha-smooth muscle actin were studied. RESULTS: Although the ALT and AST values in the group administered CCl4 were significantly higher than in all the other groups (P<0.05), there was no significant difference between the control group and the groups administered CCl4 combined with L-carnitine, N-acetylcysteine and genistein (P>0.05). There were significant differences in the levels of TNF alpha, PDGF-BB and IL-6 (P<0.05) between the CCl4 group and the groups with L carnitine, N-acetylcysteine and genistein added to CCl4. N-acetylcysteine and genistein had positive effects on the oxidant/antioxidant status and on liver necrosis and fibrosis scores. CONCLUSIONS: In our study, L-carnitine, N acetylcysteine and genistein showed significant protective effects in liver fibrosis induced by CCl4. PMID- 24239321 TI - Long-term consequences of the right ventricular pacing mania of the 1990s for obstructive hypertrophic cardiomyopathy. PMID- 24239320 TI - Prevalence of the apolipoprotein E Arg145Cys dyslipidemia at-risk polymorphism in African-derived populations. AB - Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p <0.007) and the New York African American R145C subjects had an average of 52% greater fasting triglyceride levels than the New York African-American controls (p <0.002). From these observations, likely millions of people worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia. PMID- 24239322 TI - Brain dysplasia evoked by gamma irradiation at different stages of prenatal development leads to different tonic and clonic seizure reactivity. AB - Rats with brain dysplasia evoked by interruption of different stages of prenatal neurogenesis show characteristic variations in susceptibility to seizures depending on the neurochemical specificity of pharmacological agents used to evoke seizures. To verify a discrepancy between the data obtained using different pharmacological models, neurochemically neutral electroshocks were applied here. To produce brain dysplasia of different degrees, pregnant Wistar rats were exposed to a single 1.0Gy dose of gamma rays on gestation days 13, 15, 17 or 19. From the postnatal day 60, their male offspring (E13s, E15s, E17s and E19s, respectively) were subjected to 21 daily electrical stimulations to evoke seizures. Profiles of tonic and clonic reactivity to electrical stimulation significantly differed from those observed following pilocarpine or kainic acid administration. E17s showed minimal intensity of tonic but maximal of clonic responses. On the contrary, very high tonic and low clonic reactivity was observed in E13s and E15s. Periventricular nodular heterotopias (PNHs) were observed exclusively in E15s and E17s. Generally, the size of PNHs was correlated positively with susceptibility to tonic seizures but negatively with susceptibility to clonic seizures. Analogous correlations with the size of the neocortex were opposite. E13s and E19s had brains devoid PNHs but showed high tonic seizure susceptibility similar to that in E15s. It can therefore be concluded that PNHs modified the type of seizure reactivity from tonic to clonic, depending of their size, but the presence of PNHs was not necessary for the development of seizure susceptibility itself. PMID- 24239323 TI - Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. AB - BACKGROUND: The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. METHODS: We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. FINDINGS: The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290-2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49-91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7-42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0.8-1.3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1.2-1.5. INTERPRETATION: By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. FUNDING: Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences. PMID- 24239324 TI - Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double blind, dose-ranging trial. AB - BACKGROUND: Primaquine is the only available drug that clears mature Plasmodium falciparum gametocytes in infected human hosts, thereby preventing transmission of malaria to mosquitoes. However, concerns about dose-dependent haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiencies have limited its use. We assessed the dose-response association of single-dose primaquine for gametocyte clearance and for safety in P falciparum malaria. METHODS: We undertook this randomised, double-blind, placebo-controlled trial with four parallel groups in Jinja district, eastern Uganda. We randomly allocated Ugandan children aged 1-10 years with uncomplicated falciparum malaria and normal G6PD enzyme function to receive artemether-lumefantrine, combined with either placebo or with 0.1 mg/kg, 0.4 mg/kg, or 0.75 mg/kg (WHO reference dose) primaquine base. Randomisation was done with computer-generated four-digit treatment assignment codes allocated to random dose groups in block sizes of 16. Study staff who provided care or assessed outcomes and the participants remained masked to the intervention group after assignment. The primary efficacy endpoint was the non inferiority of the mean duration of gametocyte carriage in the test doses compared with the reference group of 0.75 mg primaquine per kg, with a non inferiority margin of 2.5 days. The primary safety endpoint was the superiority of the arithmetic mean maximum decrease in haemoglobin concentration from enrolment to day 28 of follow-up in the primaquine treatment groups compared with placebo, with use of significance testing of pairwise comparisons with a cutoff of p=0.05. The trial is registered with ClinicalTrials.gov, number NCT01365598. FINDINGS: We randomly allocated 468 participants to receive artemether lumefantrine combined with placebo (119 children) or with 0.1 mg/kg (116), 0.4 mg/kg (116), or 0.75 mg/kg (117) primaquine base. The mean duration of gametocyte carriage was 6.6 days (95% CI 5.3-7.8) in the 0.75 mg/kg reference group, 6.3 days (5.1-7.5) in the 0.4 mg/kg primaquine group (p=0.74), 8.0 days (6.6-9.4) in the 0.1 mg/kg primaquine group (p=0.14), and 12.4 days (9.9-15.0) in the placebo group (p<0.0001). No children showed evidence of treatment-related haemolysis, and the mean maximum decrease in haemoglobin concentration was not associated with the dose of primaquine received-it did not differ significantly compared with placebo (10.7 g/L, SD 11.1) in the 0.1 mg/kg (11.4 g/L, 9.4; p=0.61), 0.4 mg/kg (11.3 g/L, 10.0; p=0.67), or 0.75 mg/kg (12.7 g/L, 8.2; p=0.11) primaquine groups. INTERPRETATION: We conclude that 0.4 mg/kg primaquine has similar gametocytocidal efficacy to the reference 0.75 mg/kg primaquine dose, but a dose of 0.1 mg/kg was inconclusive for non-inferiority. Our findings call for the prioritisation of further trials into the efficacy and safety of doses of primaquine between 0.1 mg/kg and 0.4 mg/kg (including the dose of 0.25 mg/kg recently recommended by WHO), in view of the potential for widespread use of the drug to block malaria transmission. FUNDING: Wellcome Trust and the Bill & Melinda Gates Foundation. PMID- 24239325 TI - The epidemiology of MERS-CoV. PMID- 24239326 TI - Single low-dose primaquine to reduce malaria transmission. PMID- 24239328 TI - Mortality rates between treated post-traumatic stress disorder Israeli male veterans compared to non-diagnosed veterans. AB - The literature suggests that post-traumatic stress disorder (PTSD) is associated with increased mortality. However, to date, mortality rates amongst veterans diagnosed with post-traumatic stress disorder have not been reported for Israeli veterans, who bear a different profile than veterans from other countries. This study aims to evaluate age-adjusted mortality rates amongst Israeli Defense Forces veterans with and without PTSD diagnosis. The study was carried out in a paired sample design with 2457 male veterans with treated PTSD and 2457 matched male veterans without a PTSD diagnosis. Data on PTSD and non-PTSD veterans was collected from the Rehabilitation Division of the Israeli Ministry of Defense (MOD) and the Israeli Defense Forces' (IDF) special unit for treatment of combat stress reaction. Mortality data were collected from the Ministry of the Interior (MOI) computerized database. Comparison of mortality rates between PTSD and non PTSD veterans was done using paired observations survival analysis by applying a proportional hazards regression model. Overall no statistically significant difference in mortality rates was found between veterans with treated PTSD and veterans without PTSD. These findings hold even when excluding veterans who died in battle and including non-PTSD veterans who died before their matched PTSD veteran was diagnosed. However, among pairs with similar military jobs PTSD group had significantly less mortality. The results of this large national cohort suggest that treated PTSD is not associated with increased mortality. We submit that the lack of this association represents the "net" pathophysiology of PTSD due to the unique characteristics of the sample. PMID- 24239327 TI - Pathogenesis of influenza-induced acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is a fatal complication of influenza infection. In this Review we provide an integrated model for its pathogenesis. ARDS involves damage to the epithelial-endothelial barrier, fluid leakage into the alveolar lumen, and respiratory insufficiency. The most important part of the epithelial-endothelial barrier is the alveolar epithelium, strengthened by tight junctions. Influenza virus targets these epithelial cells, reducing sodium pump activity, damaging tight junctions, and killing infected cells. Infected epithelial cells produce cytokines that attract leucocytes--neutrophils and macrophages--and activate adjacent endothelial cells. Activated endothelial cells and infiltrated leucocytes stimulate further infiltration, and leucocytes induce production of reactive oxygen species and nitric oxide that damage the barrier. Activated macrophages also cause direct apoptosis of epithelial cells. This model for influenza-induced ARDS differs from the classic model, which is centred on endothelial damage, and provides a rationale for therapeutic intervention to moderate host response in influenza-induced ARDS. PMID- 24239329 TI - Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. AB - Tesofensine (TE) is a novel triple monoamine re-uptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine, norepinephrine, and serotonin. In recent preclinical and clinical evaluations TE showed a robust anti-obesity effect, but the specific mechanism of this triple monoamine re-uptake inhibitor still needs to be further elucidated. This positron emission tomography (PET) study, using [11C]betaCIT-FE, aimed to assess the degree of the dopamine transporter (DAT) occupancy, at constant TE plasma levels, following different oral, multiple doses of TE during totally 8-12 days. In addition, the relationships between DAT occupancy and TE plasma concentrations, or doses, were investigated to enable assessment of DAT occupancies in subsequent clinical trials. The results demonstrated that TE induced a dose-dependent blockade of DAT following multiple doses of 0.125-1 mg TE at anticipated steady-state conditions. The mean striatal DAT occupancy varied dose-dependently between 18% and 77%. A sigmoid E(max) model well described the relationship between striatal DAT occupancy and TE plasma concentrations or doses. It was estimated that the maximum achievable DAT occupancy was about 80% and that half of this effect was accomplished by approximately 0.25 mg TE and a plasma drug concentration of 4 ng/ml. The results indicated an important mechanism of action of TE on DAT. Further, these results suggest that the previously reported dose-dependent weight loss, in TE treated subjects, was in part mediated by an up-regulation of dopaminergic pathways due to enhanced amounts of synaptic dopamine after blockade of DAT. PMID- 24239330 TI - IUD use in France: women's and physician's perspectives. AB - OBJECTIVE: While the intra-uterine device (IUD) is the second most popular contraceptive method in France, its use remains low among women most at risk of unintended pregnancies. Acknowledging the conjoint role of women and physicians in contraceptive decision making, we investigate the determinants of IUD use and IUD recommendations from the user and prescriber perspectives. STUDY DESIGN: Data are drawn from 2 national probability surveys (population-based and physician surveys) on sexual and reproductive health in France. The population based survey comprised 3,563 women ages 15-49 at risk of an unintended pregnancy in 2010 and the physician survey included 364 general practitioners (GPs) and 401 gynecologists practicing in private offices in 2010-2011. Analyses were performed using logistic regression models. RESULTS: Altogether, 21.4% of women were IUD users, with substantial differences by age and parity. Less than 1% of young women (<25 years) and 3% of nulliparous were current IUD users in 2010. The odds of IUD use were four times higher in women followed by a gynecologist as compared to a GP. Mirroring these results, gynecologists were more likely to recommend IUDs than GPs. Misconception about IUD risks was widespread among women and providers. Medical training and information, professional practice settings, and ever use of IUDs also informed physician's likelihood of recommending IUDs, regardless of specialty. CONCLUSIONS: The study reveals the intersection of individual and professional influences on contraceptive use patterns. The considerable age discrepancy in IUD use in France, with very few young women most at risk of an unintended pregnancy using the method, reflects a knowledge gap shared by users and providers. These findings suggest there are significant opportunities to improve contraceptive care in France. IMPLICATIONS: This study stresses the need to inform women and doctors about the benefits and risks of IUDs for all women. Substantial efforts are required to improve the medical curriculum, in order to promote evidenced based family planning counseling and provide GPs with the technical skills to insert IUDs. PMID- 24239331 TI - Variation in prescription contraceptive pricing across Florida ZIP code income groups. AB - BACKGROUND: The purpose of this study was to explore average monthly cost of commonly prescribed oral and transvaginal contraceptives, across ZIP code income groups, in Florida. STUDY DESIGN: In March, 2011, the MyFloridarx.com database was searched to assess monthly prices of seven commonly prescribed contraceptives charged by Florida pharmacies. RESULTS: With the exception of TNRG/EE 35 (chi(2)[4, N=401]=18.72, p=.00), monthly costs of contraceptives did not vary significantly across Florida ZIP code median income quintile groups. CONCLUSION: Overall, while there was little variability in retail pharmacy prices in Florida for seven commonly prescribed contraceptives, monthly costs of individual contraceptives varied widely. IMPLICATIONS: This report found little variability, across ZIP codes, in retail pharmacy prices in Florida for seven commonly prescribed contraceptives, but the monthly costs of individual contraceptives varied widely. It is paramount that clinicians consider costs when discussing contraceptive options with their patients. PMID- 24239332 TI - Endogenous female prostate-specific antigen from female ejaculate may confound the use of prostate-specific antigen as a biomarker of exposure to semen. PMID- 24239333 TI - Impaired macrophage production of anti-atherosclerotic interleukin-10 induced by coronary intraplaque hemorrhage in patients with acute coronary syndrome and hyperglycemia. AB - BACKGROUND: Coronary intraplaque hemorrhage (IPH) accelerates atherosclerosis. Extracellular hemoglobin (Hb) released by IPH is cleared by macrophages with CD163 receptors. This process provokes secretion of the anti-atherosclerotic cytokine interleukin (IL)-10. The present study aimed to investigate the relationship between macrophage accumulation and IL-10 production provoked by IPH in plaques obtained from acute coronary syndrome (ACS) patients with hyperglycemia. METHODS: In 50 ACS patients, atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI). The debris was stained with antibodies to CD163, glycophorin A (GPA, a marker of IPH) and IL-10. %CD163 was defined as the ratios of CD163-positive cells to all cells. %IL-10 and %GPA were defined as the ratio of positively stained areas per total tissue area. Based on glycosylated Hb [HbA1c (NGSP)] >= 6.5%, fasting blood sugar (FBS) >= 126 mg/dL, and insulin resistance (HOMA-IR>2.5), patients were divided into a diabetes mellitus (DM) group (N = 18, HbA1c >= 6.5% or FBS >= 126 mg/dL), an insulin resistance (IR) group (N = 15, HOMA-IR>2.5, HbA1c<6.5%, and FBS< 126 mg/dL), and a normal (NR) group (N = 17). RESULTS: Compared to the NR group, %GPA and %CD163 were increased in the DM and IR groups. %IL-10 was similar among the three groups. However, %IL-10/%CD163 ratios were decreased in the DM (2.5 +/- 0.6, P = 0.01) and IR (2.7 +/- 0.8, P = 0.02) groups compared to the NR group (5.8 +/- 4.7). Only in the NR group was there a significant correlation between %IL-10 and %CD163. CONCLUSIONS: Impairment of the anti-inflammatory effect provoked by IPH contributes to premature atherosclerosis even in the IR group. PMID- 24239334 TI - Image-guided regularization level set evolution for MR image segmentation and bias field correction. AB - Magnetic resonance (MR) image segmentation is a crucial step in surgical and treatment planning. In this paper, we propose a level-set-based segmentation method for MR images with intensity inhomogeneous problem. To tackle the initialization sensitivity problem, we propose a new image-guided regularization to restrict the level set function. The maximum a posteriori inference is adopted to unify segmentation and bias field correction within a single framework. Under this framework, both the contour prior and the bias field prior are fully used. As a result, the image intensity inhomogeneity can be well solved. Extensive experiments are provided to evaluate the proposed method, showing significant improvements in both segmentation and bias field correction accuracies as compared with other state-of-the-art approaches. PMID- 24239335 TI - Exchange-mediated contrast in CEST and spin-lock imaging. AB - PURPOSE: Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1rho) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. METHODS: Simulations and experimental measurements at 9.4 T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. RESULTS: The simulations and experimental measurements confirm that both CEST and R1rho measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. >2 ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (<2 ppm) and exchange is in the intermediate-to-fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CONCLUSION: CEST and R1rho measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1rho-dependent acquisitions can be employed to selectively portray protons of specific exchange rates. PMID- 24239337 TI - Quantifying liver fibrosis through the application of texture analysis to diffusion weighted imaging. AB - The purpose of this study was to evaluate the potential utility of texture analysis of parametric apparent diffusion coefficient (ADC) maps in quantifying hepatic fibrosis. To this end, using ex vivo murine liver tissues from a dietary model of hepatic fibrosis, an array of texture analysis techniques, including histogram-based, gray-level co-occurrence matrix-based, and gray-level run-length based features, was used to evaluate correlations with liver fibrosis. Moderate to very strong correlation between several of the texture-based features and both subjective as well as digital image analysis-based assessments of hepatic fibrosis was demonstrated. This rigorous study of texture analysis applied to parametric ADC maps in a liver fibrosis model study demonstrates and validates the potential utility of texture-based features for the noninvasive, quantitative assessment of hepatic fibrosis. PMID- 24239336 TI - MRI detection of brown adipose tissue with low fat content in newborns with hypothermia. AB - PURPOSE: To report the observation of brown adipose tissue (BAT) with low fat content in neonates with hypoxic-ischemic encephalopathy (HIE) after they have undergone hypothermia therapy. MATERIALS AND METHODS: The local ethics committee approved the imaging study. Ten HIE neonates (3 males, 7 females, age range: 2 3days) were studied on a 3-T MRI system using a low-flip-angle (3 degrees ) six echo proton-density-weighted chemical-shift-encoded water-fat pulse sequence. Fat signal fraction (FF) measurements of supraclavicular and interscapular (nape) BAT and adjacent subcutaneous white adipose tissues (WAT) were compared to those from five non-HIE neonates, two recruited for the present investigation and three from a previous study. RESULTS: In HIE neonates, the FF range for the supraclavicular, interscapular, and subcutaneous regions was 10.3%-29.9%, 28.0%-57.9%, and 62.6% 88.0%, respectively. In non-HIE neonates, the values were 23.7%-42.2% (p=0.01), 45.4%-59.5% (p=0.06), and 67.8%-86.3% (p=0.38), respectively. On an individual basis, supraclavicular BAT FF was consistently the lowest, interscapular BAT values were higher, and subcutaneous WAT values were the highest (p<0.01). CONCLUSION: We speculate that hypothermia therapy in HIE neonates likely promotes BAT-mediated non-shivering thermogenesis, which subsequently leads to a depletion of the tissue's intracellular fat stores. We believe that this is consequently reflected in lower FF values, particularly in the supraclavicular BAT depot, in contrast to non-HIE neonates. PMID- 24239338 TI - The tragedy of adaptability. PMID- 24239339 TI - Value and evidence-based medicine: a call for shared responsibility. PMID- 24239340 TI - Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. AB - STUDY OBJECTIVE: Allergic reactions are common presentations to the emergency department (ED). An unknown proportion of patients will develop biphasic reactions, and patients are often monitored for prolonged periods to manage potential reactions. We seek to determine the incidence of clinically important biphasic reactions. METHODS: Consecutive adult patients presenting to 2 urban EDs with allergic reactions during a 5-year period were identified. Encounters were dichotomized as "anaphylaxis" or "allergic reaction" with an explicit algorithm. A comprehensive chart review was conducted on each index and all subsequent visits to detail patient presentations, comorbidities, ED management, and predefined clinically important biphasic reactions. Regional and provincial databases were linked to identify subsequent ED visits and deaths within a 7-day period. The primary outcome was the proportion of patients with a clinically important biphasic reaction, and the secondary outcome was mortality. RESULTS: Of 428,634 ED visits, 2,819 (0.66%) encounters were reviewed (496 anaphylactic and 2,323 allergic reactions). Overall, 185 patients had at least 1 subsequent visit for allergic symptoms. Five clinically important biphasic reactions were identified (0.18%; 95% confidence interval [CI] 0.07% to 0.44%), with 2 occurring during the ED visit and 3 postdischarge. There were no fatalities (95% CI 0% to 0.17%). In the anaphylaxis and allergic reaction groups, clinically important biphasic reactions occurred in 2 patients (0.40%; 95% CI 0.07% to 1.6%) and 3 patients (0.13%; 95% CI 0.03% to 0.41%), respectively. CONCLUSION: Among ED patients with allergic reactions or anaphylaxis, clinically important biphasic reactions and fatalities are rare. Our data suggest that prolonged routine monitoring of patients whose symptoms have resolved is likely unnecessary for patient safety. PMID- 24239342 TI - Hybrid anticancer 1,2-diazine derivatives with multiple mechanism of action. Part 3. AB - Antitumour chemotherapy is nowadays a very active field of research, DNA targeting drugs being the most widely used group in therapy. The design, synthesis and anticancer activity of a new class of anticancer derivatives with pyrrolo-1,2-diazine and benzoquinone skeleton is presented. The synthesis is direct and efficient, involving an alkylation followed by a [3+2] dipolar cycloaddition. The penta- and tetra-cyclic pyrrolo-1,2-diazine were evaluated for their in vitro anticancer activity against an NCI 60 human tumour cell line panel. The pentacyclic-1,2-diazine exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM and Breast Cancer MCF7. We hypothesize that these molecules will exert their anticancer activity through multiple mechanisms of action: intercalating the DNA, inhibiting the topoisomerase enzymes and, destroying the DNA strands via electron transfer mechanism. However, the intercalation with the DNA seems to prevail in competition with the others mechanisms. PMID- 24239341 TI - Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission. AB - STUDY OBJECTIVE: Older adults are frequently hospitalized from the emergency department (ED) after an episode of unexplained syncope. Current admission patterns are costly, with little evidence of benefit. We hypothesize that an ED observation syncope protocol will reduce resource use without adversely affecting patient-oriented outcomes. METHODS: This randomized trial at 5 EDs compared an ED observation syncope protocol to inpatient admission for intermediate-risk adults (>=50 years) presenting with syncope or near syncope. Primary outcomes included inpatient admission rate and length of stay. Secondary outcomes included 30-day and 6-month serious outcomes after hospital discharge, index and 30-day hospital costs, 30-day quality-of-life scores, and 30-day patient satisfaction. RESULTS: Study staff randomized 124 patients. Observation resulted in a lower inpatient admission rate (15% versus 92%; 95% confidence interval [CI] difference -88% to 66%) and shorter hospital length of stay (29 versus 47 hours; 95% CI difference 28 to -8). Serious outcome rates after hospital discharge were similar for observation versus admission at 30 days (3% versus 0%; 95% CI difference -1% to 8%) and 6 months (8% versus 10%; 95% CI difference -13% to 9%). Index hospital costs in the observation group were $629 (95% CI difference -$1,376 to -$56) lower than in the admission group. There were no differences in 30-day quality-of life scores or in patient satisfaction. CONCLUSION: An ED observation syncope protocol reduced the primary outcomes of admission rate and hospital length of stay. Analyses of secondary outcomes suggest reduction in index hospital costs, with no difference in safety events, quality of life, or patient satisfaction. Our findings suggest that an ED observation syncope protocol can be replicated and safely reduce resource use. PMID- 24239343 TI - Clinical evaluation of a novel intraoperative handheld gamma camera for sentinel lymph node biopsy. AB - OBJECTIVE: Preoperative lymphoscintigraphy (PLS) combined with intraoperative gamma probe (GP) localization is standard procedure for localizing the sentinel lymph nodes (SLN) in melanoma and breast cancer. In this study, we evaluated the ability of a novel intraoperative handheld gamma camera (IHGC) to image SLNs during surgery. METHODS: The IHGC is a small-field-of-view camera optimized for real-time imaging of lymphatic drainage patterns. Unlike conventional cameras, the IHGC can acquire useful images in a few seconds in a free-running fashion and be moved manually around the patient to find a suitable view of the node. Thirty nine melanoma and eleven breast cancer patients underwent a modified SLN biopsy protocol in which nodes localized with the GP were imaged with the IHGC. The IHGC was also used to localize additional nodes that could not be found with the GP. RESULTS: The removal of 104 radioactive SLNs was confirmed ex vivo by GP counting. In vivo, the relative node detection sensitivity was 88.5 (82.3, 94.6)% for the IHGC (used in conjunction with the GP) and 94.2 (89.7, 98.7)% for the GP alone, a difference not found to be statistically significant (McNemar test, p = 0.24). CONCLUSION: Small radioactive SLNs can be visualized intraoperatively using the IHGC with exposure time of 20 s or less, with no significant difference in node detection sensitivity compared to a GP. The IHGC is a useful complement to the GP, especially for SLNs that are difficult to locate with the GP alone. PMID- 24239344 TI - Parkinson's patients cope with daylight saving time. AB - Disturbances of the circadian timing system following daylight saving time (DST) may influence the symptoms of Parkinson's disease (PD). To address this question, we compared the severity of motor fluctuations and non-motor symptoms both before and after the time change. Total daily "off-time" based on diaries, excessive daytime sleepiness (Epworth Sleepiness Scale), depressive symptoms (Beck Depression Inventory), and psychosis associated with PD were assessed both before and after the DST. Eighty-three PD patients (mean age, 67+/-7.7years; mean disease duration, 10.4+/-6.4years) were included. Thirty-six patients had motor fluctuations (mean daily "off-time", 4.8+/-2.4h/day). There was no significant variation of the total daily "off-time" (2.5+/-2.6h/day versus 2.5+/-2.7h/day), ESS (8.3+/-4.8 versus 8.1+/-4.9), BDI (10.4+/-6.2 versus 10.0+/-6.9), or PAPD (1.4+/-1.6 versus 1.1+/-1.6) scores (P>0.05) after DST. Our results suggest that PD patients cope relatively well with DST. PMID- 24239345 TI - [Foreword. Wilson's disease]. PMID- 24239346 TI - GRIN2A, a green semaphore on the lumping route to idiopathic focal epilepsy in childhood. PMID- 24239347 TI - [Electrodiagnostic criteria for early diagnosis of bulbar-onset ALS: a comparison of El Escorial, revised El Escorial and Awaji algorithm]. AB - INTRODUCTION: Diagnosis of bulbar ALS is difficult at the early stage of the disease. According to guidelines, early diagnosis is better in view to optimize the management of affected patients. To improve the sensitivity without losing specificity of the prior criteria, the Board of Awaji has proposed modified electrodiagnostic criteria for ALS. The aim of this study was to evaluate the contribution of needle electromyography in early diagnosis of bulbar ALS by comparing the El Escorial criteria (EEC), Revised El Escorial Criteria (R-EEC) and Awaji algorithm (AA). METHODS: In a retrospective study, we analysed clinical and electrophysiological data of 46 patients followed in our center for a bulbar onset ALS seen for the first time between January 2007 and February 2011. All these patients had bulbar-onset ALS probable or certain at the last follow-up. All data were collected during the first clinical examination and the first electrophysiological study. RESULTS: Mean age of the population was 69 (37 90years, sex ratio: 0.91). Using the EEC, 9 patients were diagnosed as definite or probable ALS at the first consultation. Applying the R-EEC, 13 patients were diagnosed as definite or probable ALS and using the AA, 23 patients were diagnosed as definite or probable ALS. The sensitivity of the EEC was 19.5%, the R-EEC was 28.2% and for AA was 49.98%. CONCLUSION: AA are more sensitive in early diagnosis of bulbar ALS compared to R-EEC with the contribution of ENMG and when fasciculations are considered as evidence of spontaneous activity. Such an approach can contribute to accelerate an optimal management of the disease. AA are a breakthrough in the diagnosis of ALS especially in the bulbar-onset forms. PMID- 24239348 TI - A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response in vivo. AB - A fundamental limitation in devising new therapeutic strategies for killing cancer cells with DNA damaging agents is the need to identify synthetic lethal interactions between tumor-specific mutations and components of the DNA damage response (DDR) in vivo. The stress-activated p38 mitogen-activated protein kinase (MAPK)/MAPKAP kinase-2 (MK2) pathway is a critical component of the DDR network in p53-deficient tumor cells in vitro. To explore the relevance of this pathway for cancer therapy in vivo, we developed a specific gene targeting strategy in which Cre-mediated recombination simultaneously creates isogenic MK2-proficient and MK2-deficient tumors within a single animal. This allows direct identification of MK2 synthetic lethality with mutations that promote tumor development or control response to genotoxic treatment. In an autochthonous model of non-small-cell lung cancer (NSCLC), we demonstrate that MK2 is responsible for resistance of p53-deficient tumors to cisplatin, indicating synthetic lethality between p53 and MK2 can successfully be exploited for enhanced sensitization of tumors to DNA-damaging chemotherapeutics in vivo. PMID- 24239349 TI - Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. AB - During miRNA biogenesis, the microprocessor complex (MC), which is composed minimally of Drosha, an RNase III enzyme, and DGCR8, a double-stranded RNA binding protein, cleaves the primary miRNA (pri-miRNA) in order to release the pre-miRNA stem-loop structure. Using phosphoproteomics, we mapped 23 phosphorylation sites on full-length human DGCR8 expressed in insect or mammalian cells. DGCR8 can be phosphorylated by mitogenic ERK/MAPK, indicating that DGCR8 phosphorylation may respond to and integrate extracellular cues. The expression of phosphomimetic DGCR8 or inhibition of phosphatases increased the cellular levels of DGCR8 and Drosha proteins. Increased levels of phosphomimetic DGCR8 were not due to higher mRNA levels, altered DGCR8 localization, or DGCR8's ability to self-associate, but rather to an increase in protein stability. MCs incorporating phosphomutant or phosphomimetic DGCR8 were not altered in specific processing activity. However, HeLa cells expressing phosphomimetic DGCR8 exhibited a progrowth miRNA expression profile and increased proliferation and scratch closure rates relative to cells expressing phosphomutant DGCR8. PMID- 24239350 TI - The presenilin-1 DeltaE9 mutation results in reduced gamma-secretase activity, but not total loss of PS1 function, in isogenic human stem cells. AB - Presenilin 1 (PS1) is the catalytic core of gamma-secretase, which cleaves type 1 transmembrane proteins, including the amyloid precursor protein (APP). PS1 also has gamma-secretase-independent functions, and dominant PS1 missense mutations are the most common cause of familial Alzheimer's disease (FAD). Whether PS1 FAD mutations are gain- or loss-of-function remains controversial, primarily because most studies have relied on overexpression in mouse and/or nonneuronal systems. We used isogenic euploid human induced pluripotent stem cell lines to generate and study an allelic series of PS1 mutations, including heterozygous null mutations and homozygous and heterozygous FAD PS1 mutations. Rigorous analysis of this allelic series in differentiated, purified neurons allowed us to resolve this controversy and to conclude that FAD PS1 mutations, expressed at normal levels in the appropriate cell type, impair gamma-secretase activity but do not disrupt gamma-secretase-independent functions of PS1. Thus, FAD PS1 mutations do not act as simple loss of PS1 function but instead dominantly gain an activity toxic to some, but not all, PS1 functions. PMID- 24239351 TI - Hijacking multivesicular bodies enables long-term and exosome-mediated long distance action of anthrax toxin. AB - Anthrax lethal toxin is a classical AB toxin comprised of two components: protective antigen (PA) and lethal factor (LF). Here, we show that following assembly and endocytosis, PA forms a channel that translocates LF, not only into the cytosol, but also into the lumen of endosomal intraluminal vesicles (ILVs). These ILVs can fuse and release LF into the cytosol, where LF can proteolyze and disable host targets. We find that LF can persist in ILVs for days, fully sheltered from proteolytic degradation, both in vitro and in vivo. During this time, ILV-localized LF can be transmitted to daughter cells upon cell division. In addition, LF-containing ILVs can be delivered to the extracellular medium as exosomes. These can deliver LF to the cytosol of naive cells in a manner that is independent of the typical anthrax toxin receptor-mediated trafficking pathway, while being sheltered from neutralizing extracellular factors of the immune system. PMID- 24239352 TI - Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and beta-arrestin 1 pathway. AB - G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (deltaORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and beta-arrestin 1 (beta-arr1) to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca(2+) channels in DRGs. Agonists of opioid receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and beta-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of deltaOR or ORL1 agonists were enhanced in the absence of beta-arr1 or prevented by inhibiting ROCK. This pathway allows deltaOR and ORL1 agonists to rapidly regulate receptor function. PMID- 24239353 TI - A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease. AB - Expression of the human Parkinson-disease-associated protein alpha-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal beta and beta' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express alpha-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the beta' lobe, but not the beta or gamma lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body beta' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies. PMID- 24239354 TI - Context-specific BAFF-R signaling by the NF-kappaB and PI3K pathways. AB - BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the noncanonical NF-kappaB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via phosphatidylinositol 3-kinase (PI3K), and that coinactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff(-/-) animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner. PMID- 24239355 TI - Structural analysis uncovers lipid-binding properties of Notch ligands. AB - The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles in cell-fate determination, stem cell maintenance, immune system activation, and angiogenesis. Signals are initiated by extracellular interactions of the Notch receptor with Delta/Serrate/Lag-2 (DSL) ligands, whose structure is highly conserved throughout evolution. To date, no structure or activity has been associated with the extreme N termini of the ligands, even though numerous mutations in this region of Jagged-1 ligand lead to human disease. Here, we demonstrate that the N terminus of human Jagged-1 is a C2 phospholipid recognition domain that binds phospholipid bilayers in a calcium-dependent fashion. Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. These results reveal an important and previously unsuspected role for phospholipid recognition in control of this key signaling system. PMID- 24239357 TI - Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis. AB - The small GTPase Rho and mDia2, a Rho-regulated actin nucleator, function as critical regulators of cytokinesis in cultured cells. However, their involvement in cytokinesis during mammalian development remains unknown. Here, we generated mice deficient in mDia2 and examined the role of Rho signaling in cytokinesis during development. mDia2-deficient mice survive until embryonic day 11.5 (E11.5), exhibit severe anemia with multinucleate erythroblasts, and die in utero by E12.5. mDia2-deficient erythroid cells differentiate normally, though in a delayed manner, but exhibit cytokinesis failure with decreased accumulation of F actin in the cleavage furrow during late differentiation from proerythroblasts. On the other hand, inactivation of Rho induces cytokinesis failure from the earlier progenitor stage. mDia2-deficient erythroblasts, however, are able to enucleate their nuclei. Our findings have thus revealed that mDia2 functions critically in cytokinesis in vivo during erythropoiesis and further suggest that the cytokinesis mechanism in development diverges downstream of Rho. They also demonstrate that cytokinesis and enucleation utilize different mechanisms. PMID- 24239356 TI - Molecular basis for DNA double-strand break annealing and primer extension by an NHEJ DNA polymerase. AB - Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break (DSB) repair pathways. The mechanisms by which breaks are competently brought together and extended during NHEJ is poorly understood. As polymerases extend DNA in a 5'-3' direction by nucleotide addition to a primer, it is unclear how NHEJ polymerases fill in break termini containing 3' overhangs that lack a primer strand. Here, we describe, at the molecular level, how prokaryotic NHEJ polymerases configure a primer-template substrate by annealing the 3' overhanging strands from opposing breaks, forming a gapped intermediate that can be extended in trans. We identify structural elements that facilitate docking of the 3' ends in the active sites of adjacent polymerases and reveal how the termini act as primers for extension of the annealed break, thus explaining how such DSBs are extended in trans. This study clarifies how polymerases couple break-synapsis to catalysis, providing a molecular mechanism to explain how primer extension is achieved on DNA breaks. PMID- 24239358 TI - TORC1 inhibits GSK3-mediated Elo2 phosphorylation to regulate very long chain fatty acid synthesis and autophagy. AB - Very long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell's metabolic demand remains unknown. The goal of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters the ceramide spectrum, reflecting aberrant VLCFA synthesis. Furthermore, VLCFA depletion results in constitutive activation of autophagy, which requires sphingoid base phosphorylation. This constitutive activation of autophagy diminishes cell survival, indicating that VLCFAs serve to dampen the amplitude of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis. PMID- 24239359 TI - Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells. AB - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) and MyoD(+) myogenic progenitors by expressing oncogenic Kras(G12D) and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taking them together, we have established mouse models of soft tissue sarcoma from muscle stem and progenitor cells. PMID- 24239361 TI - In vivo thermal ablation monitoring using ultrasound echo decorrelation imaging. AB - Previous work indicated that ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool was assessed. RFA was performed on normal swine liver (N = 5), and ultrasound ablation using image-ablate arrays was performed on rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC = 0.832 and 0.776 for RFA and ultrasound ablation, respectively) than using integrated backscatter (AUROC = 0.734 and 0.494). PMID- 24239360 TI - 3-D transcranial ultrasound imaging with bilateral phase aberration correction of multiple isoplanatic patches: a pilot human study with microbubble contrast enhancement. AB - With stroke currently the second-leading cause of death globally, and 87% of all strokes classified as ischemic, the development of a fast, accessible, cost effective approach for imaging occlusive stroke could have a significant impact on health care outcomes and costs. Although clinical examination and standard computed tomography alone do not provide adequate information for understanding the complex temporal events that occur during an ischemic stroke, ultrasound imaging is well suited to the task of examining blood flow dynamics in real time and may allow for localization of a clot. A prototype bilateral 3-D ultrasound imaging system using two matrix array probes on either side of the head allows for correction of skull-induced aberration throughout two entire phased array imaging volumes. We investigated the feasibility of applying this custom correction technique in five healthy volunteers with Definity microbubble contrast enhancement. Subjects were scanned simultaneously via both temporal acoustic windows in 3-D color flow mode. The number of color flow voxels above a common threshold increased as a result of aberration correction in five of five subjects, with a mean increase of 33.9%. The percentage of large arteries visualized by 3-D color Doppler imaging increased from 46% without aberration correction to 60% with aberration correction. PMID- 24239362 TI - Microbubble type and distribution dependence of focused ultrasound-induced blood brain barrier opening. AB - Focused ultrasound, in the presence of microbubbles, has been used non-invasively to induce reversible blood-brain barrier (BBB) opening in both rodents and non human primates. This study was aimed at identifying the dependence of BBB opening properties on polydisperse microbubble (all clinically approved microbubbles are polydisperse) type and distribution by using a clinically approved ultrasound contrast agent (Definity microbubbles) and in-house prepared polydisperse (IHP) microbubbles in mice. A total of 18 C57 BL/6 mice (n = 3) were used in this study, and each mouse was injected with either Definity or IHP microbubbles via the tail vein. The concentration and size distribution of activated Definity and IHP microbubbles were measured, and the microbubbles were diluted to 6 * 10(8)/mL before injection. Immediately after microbubble administration, mice were subjected to focused ultrasound with the following parameters: frequency = 1.5 MHz, pulse repetition frequency = 10 Hz, 1000 cycles, in situ peak rarefactional acoustic pressures = 0.3, 0.45 and 0.6 MPa for a sonication duration of 60 s. Contrast-enhanced magnetic resonance imaging was used to confirm BBB opening and allowed for image-based analysis. Permeability of the treated region and volume of BBB opening did not significantly differ between the two types of microbubbles (p > 0.05) at peak rarefractional acoustic pressures of 0.45 and 0.6 MPa, whereas IHP microbubbles had significantly higher permeability and opening volume (p < 0.05) at the relatively lower pressure of 0.3 MPa. The results from this study indicate that microbubble type and distribution could have significant effects on focused ultrasound-induced BBB opening at lower pressures, but less important effects at higher pressures, possibly because of the stable cavitation that governs the former. This difference may have become less significant at higher pressures, where inertial cavitation typically occurs. PMID- 24239363 TI - Electromechanical wave imaging of biologically and electrically paced canine hearts in vivo. AB - Electromechanical wave imaging (EWI) has been show capable of directly and entirely non-invasively mapping the trans mural electromechanical activation in all four cardiac chambers in vivo. In this study, we assessed EWI repeatability and reproducibility, as well as its capability of localizing electronic and, for the first time, biological pacing locations in closed-chest, conscious canines. Electromechanical activation was obtained in six conscious animals during normal sinus rhythm (NSR) and idioventricular rhythms occurring in dogs with complete heart block instrumented with electronic and biologic pacemakers (EPM and BPM respectively). After atrioventricular node ablation, dogs were implanted with an EPM in the right ventricular (RV) endocardial apex (n = 4) and two additionally received a BPM at the left ventricular (LV) epicardial base (n = 2). EWI was performed trans thoracically during NSR, BPM and EPM pacing, in conscious dogs, using an unfocused transmit sequence at 2000 frames/s. During NSR, the EW originated at the right atrium (RA), propagated to the left atrium (LA) and emerged from multiple sources in both ventricles. During EPM, the EW originated at the RV apex and propagated throughout both ventricles. During BPM, the EW originated from the LV basal lateral wall and subsequently propagated throughout the ventricles. EWI differentiated BPM from EPM and NSR and identified the distinct pacing origins. Isochrone comparison indicated that EWI was repeatable and reliable. These findings thus indicate the potential for EWI to serve as a simple, non-invasive and direct imaging technology for mapping and characterizing arrhythmias as well as the treatments thereof. PMID- 24239364 TI - Consistent regional heterogeneity of passive diastolic stretch and systolic deformation in the healthy heart: age-related changes in left ventricle contractility. AB - The consistency of the normal spatial distribution of segmental passive stretch (PreS) and systolic strain (SS) within the left ventricle was investigated and a recently proposed echocardiographic estimate of left ventricular (LV) contractility was used to detect contractility changes with age. Hereto, in 54 healthy subjects, segmental PreS and SS were measured on tissue Doppler images of six left ventricle walls. For each subject, a linear regression line was estimated through the segmental PreS and SS values. The slopes and intercepts of this PreS-SS relationship did not differ between age groups, suggesting no changes in LV contractility with age. Moreover, a consistent regional distribution of PreS was observed, with the highest values measured in the septum, resulting in a similar distribution of SS as a direct consequence of the Frank-Starling mechanism. PMID- 24239381 TI - Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. AB - blind sterile (bs) is a spontaneous autosomal-recessive mouse mutation discovered more than 30 years ago. Phenotypically, bs mice exhibit nuclear cataracts and male infertility; genetic analyses assigned the bs locus to mouse chromosome 2. In this study, we first positionally cloned the bs locus and identified a putative causative mutation in the Tbc1d20 gene. Functional analysis established the mouse TBC1D20 protein as a GTPase-activating protein (GAP) for RAB1 and RAB2, and bs as a TBC1D20 loss-of-function mutation. Evaluation of bs mouse embryonic fibroblasts (mEFs) identified enlarged Golgi morphology and aberrant lipid droplet (LD) formation. Based on the function of TBC1D20 as a RABGAP and the bs cataract and testicular phenotypes, we hypothesized that mutations in TBC1D20 may contribute to Warburg micro syndrome (WARBM); WARBM constitutes a spectrum of disorders characterized by eye, brain, and endocrine abnormalities caused by mutations in RAB3GAP1, RAB3GAP2, and RAB18. Sequence analysis of a cohort of 77 families affected by WARBM identified five distinct TBC1D20 loss-of-function mutations, thereby establishing these mutations as causative of WARBM. Evaluation of human fibroblasts deficient in TBC1D20 function identified aberrant LDs similar to those identified in the bs mEFs. Additionally, our results show that human fibroblasts deficient in RAB18 and RAB3GAP1 function also exhibit aberrant LD formation. These findings collectively indicate that a defect in LD formation/metabolism may be a common cellular abnormality associated with WARBM, although it remains unclear whether abnormalities in LD metabolism are contributing to WARBM disease pathology. PMID- 24239383 TI - Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition. AB - Amylin is a metabolic peptide hormone that is co-secreted with insulin from beta cells in the pancreas and activates many of the downstream targets of insulin. To investigate the relationship between this hormone and Alzheimer's disease (AD), we measured plasma human amylin levels in 206 subjects with AD, 64 subjects with mild cognitive impairment, and 111 subjects with no cognitive impairment and found significantly lower amylin levels among subjects with AD and mild cognitive impairment compared with the cognitively intact subjects. To investigate mechanisms underlying amylin's effects in the brain, we administered chronic infusions of the amylin analog pramlintide in the senescence-accelerated prone mouse, a mouse model of sporadic AD. Pramlintide administration improved performance in the novel object recognition task, a validated test of memory and cognition. The pramlintide-treated mice had increased expression of the synaptic marker synapsin I and the kinase cyclin-dependent kinase-5 in the hippocampus, as well as decreased oxidative stress and inflammatory markers in the hippocampus. A dose-dependent increase in cyclin-dependent kinase-5 and activation of extracellular-signal-regulated-kinases 1/2 by pramlintide treatment in vitro was also present indicating functionality of the amylin receptor in neurons. Together these results suggest that amylin analogs have neuroprotective properties and might be of therapeutic benefit in AD. PMID- 24239382 TI - Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures. AB - The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID- 24239384 TI - Metabolic abnormalities and hypoleptinemia in alpha-synuclein A53T mutant mice. AB - Parkinson's disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human alpha-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared with both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD, whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, magnetic resonance imaging analysis revealed that WT mice had significantly greater total and visceral body fat compared with SNCA mice (p < 0.007). At the age of 24 weeks SNCA mice displayed significantly increased hunger compared with WT (p < 0.03). At the age of 36 weeks, SNCA mice displayed significant hypoleptinemia compared with WT, both on a normal diet and a HCD (p < 0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared with WT, as measured in a Comprehensive Laboratory Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that alpha-synuclein pathology is sufficient to drive such metabolic abnormalities and providing an animal model for discovery of the underlying mechanisms and potential therapeutic interventions. PMID- 24239385 TI - Deficiency in homologous recombination renders Mammalian cells more sensitive to proton versus photon irradiation. AB - PURPOSE: To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation. METHODS AND MATERIALS: The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining deficient cells were analyzed after irradiation with clinically relevant, low linear energy transfer (LET) protons and 200-keV photons. RESULTS: All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR deficient cells and wild-type cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual gammaH2AX foci after irradiation. CONCLUSION: Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways. PMID- 24239386 TI - Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma. AB - PURPOSE: To compare quality of survival in "standard-risk" medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. METHODS AND MATERIALS: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. RESULTS: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). CONCLUSIONS: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life. PMID- 24239387 TI - Interfraction displacement of primary tumor and involved lymph nodes relative to anatomic landmarks in image guided radiation therapy of locally advanced lung cancer. AB - PURPOSE: To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. METHODS AND MATERIALS: In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. RESULTS: Three dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). CONCLUSIONS: Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease. PMID- 24239388 TI - Structural stability of methane hydrates in porous medium: Raman spectroscopic study. AB - Thermal and temporal stability of the methane hydrates (MH) at ambient pressure, synthesised in a spherical silica (solid and hollow, with average diameter of 70 MUm) matrix, are investigated by the Raman spectroscopy. Identical Raman spectroscopic spectral features for all the synthesized hydrate samples indicate structural resemblance irrespective of matrix. It is observed that the growth of hydrates in hollow silica matrix is homogeneous, while that with solid grain is highly heterogeneous. Temporal and thermal stability of MH depends on the silica matrix. Appearance of the Raman signatures characteristic of MH, in hollow silica, indicates that the hydrates are stable over several hours (upon preserving at 153 K and 0.1 MPa) and until ~273 K at 0.1 MPa. However, MH in solid silica matrix is highly unstable under similar P, T conditions and they are readily dissociated within 2 h. The thermal stability of these samples at 0.1 MPa is also significantly lower. PMID- 24239389 TI - Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: synthesis and SAR of novel analogs of MBX 1066 and MBX 1090. AB - The prevalence of drug-resistant bacteria in the clinic has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We have previously described a set of bisamidine antibiotics that contains a core composed of two indoles and a central linker. The first compounds of the series, MBX 1066 and MBX 1090, have potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. We have conducted a systematic exploration of the amidine functionalities, the central linker, and substituents at the indole 3-position to determine the factors involved in potent antibacterial activity. Some of the newly synthesized compounds have even more potent and broad-spectrum activity than MBX 1066 and MBX 1090. PMID- 24239391 TI - [A bit of angiography history]. PMID- 24239390 TI - Bioactive compounds from Stuhlmannia moavi from the Madagascar dry forest. AB - Bioassay-directed fractionation of the leaf and root extracts of the antiproliferative Madagascar plant Stuhlmannia moavi afforded 6-acetyl-5,8 dihydroxy-2-methoxy-7-methyl-1,4-naphthoquinone (stuhlmoavin, 1) as the most active compound, with an IC50 value of 8.1 MUM against the A2780 human ovarian cancer cell line, as well as the known homoisoflavonoid bonducellin (2) and the stilbenoids 3,4,5'-trihydroxy-3'-methoxy-trans-stilbene (3), piceatannol (4), resveratrol (5), rhapontigenin (6), and isorhapontigenin (7). The structure elucidation of all compounds was based on NMR and mass spectroscopic data, and the structure of 1 was confirmed by a single crystal X-ray analysis. Compounds 2 5 showed weak A2780 activities, with IC50 values of 10.6, 54.0, 41.0, and 74.0 MUM, respectively. Compounds 1-3 also showed weak antimalarial activity against Plasmodium falciparum with IC50 values of 23, 26, and 27 MUM, respectively. PMID- 24239392 TI - Selection of patients for percutaneous balloon mitral valvotomy: is there a definitive limit for the Wilkins score? AB - AIM: The aim of this study was to determine the early and long-term results of percutaneous balloon mitral valvotomy (PBMV) in patients with Wilkins score (WS) between 9 and 11. METHODS: We performed a retrospective review of clinical records of patients with rheumatic mitral stenosis who underwent PBMV between November 1991 and March 2008. Follow-up was obtained by telephone interview and/or clinical records. The procedure was considered unsuccessful when post procedure mitral valve area was <1.5 cm(2). RESULTS: We analyzed 124 patients, 108 (87.1%) of them women. Mean age at the time of repair was 46 +/- 11 years and mean follow-up time was 10 +/- 4 years. Before the procedure, 100 patients (80.6%) had WS <= 8 and 24 (19.4%) were in the "gray zone" (>8 and <11). Patients with WS <= 8 and patients in the gray zone had similar ages at first intervention (45 +/- 11 vs. 49 +/- 11 years; p=0.095) and follow-up time (10 +/- 4 vs. 11 +/- 5 years; p=0.55). There were no differences between groups in gender (women: 86% vs. 92%; p=0.735), or in baseline echocardiographic measurements (mitral valve area by planimetry 1.0 cm(2) [P25-P75: 0.9-1.1] vs. 0.9 [P25-P75: 0.8-1.2], p=0.514; pulmonary artery systolic pressure 53 mmHg [P25-P75: 45-63] vs. 50 [P25 P75: 44-54], p=0.823]; left atrial diameter >55 mm [16.5% vs. 13.6%, p=1.00]; mitral regurgitation [46.5% vs. 37.5%, p=0.428]) or baseline transmitral gradient (13 mmHg [P25-P75: 10-19] vs. 13 mmHg [P25-P75: 7-20]). Improvements in mitral valve area by planimetry and in hemodynamic gradient were similar in the two groups (0.91 +/- 0.39 cm(2) vs. 0.84 +/- 0.44 cm(2), p=0.55; 8.8 +/- 5.3 mmHg vs. 7.3 +/- 5.9 mmHg, p=0.275, respectively). There were no significant differences in major complications or success rates (4.0 vs. 12.5 p=0.131; 89.9% vs. 95.8%, p=0.69) or in need for urgent surgery or future reintervention (2.0 vs. 8.3%, p=0.168; 22% vs. 27.3%, p=0.594). In-hospital mortality occurred only in patients in the WS gray zone (2 [8.3%] vs. 0%, p=0.04), one death (4.2% vs. 0%, p=0.194) possibly being related to a higher WS (secondary to stroke) and the other as a consequence of peripheral vascular complication. Improvements in NYHA functional class soon after the procedure and during follow-up were similar in the two groups. Total mortality was similar in the two groups (3.1 vs. 8.7%, p=0.244). CONCLUSIONS: PBMV was a safe and effective procedure in patients in the WS gray zone. Optimal results can be achieved in these patients if they are carefully selected and operated at experienced centers. PMID- 24239393 TI - Are leptin levels a cause or an indicator of cardiovascular risk? PMID- 24239394 TI - The Cochrane Corner in the Portuguese Journal of Cardiology. PMID- 24239395 TI - Long-term follow-up after aortic coarctation repair: the unsolved issue of exercise-induced hypertension. AB - INTRODUCTION: Despite successful repair of aortic coarctation (AC), systemic hypertension (HTN) can persist in a significant percentage of patients. Exercise induced HTN is also common in these patients, although its clinical significance is still unclear. In this study we aimed to assess the prevalence of exercise induced HTN in adult patients with repaired AC. METHODS: We retrospectively reviewed the clinical records of patients aged >18 years with repaired AC followed at an adult congenital heart disease outpatient clinic in a tertiary care center. Demographic and clinical data including age at intervention, blood pressure (BP) at rest and on exercise, transthoracic echocardiogram (TTE) and treadmill exercise test results were evaluated. Exercise-induced HTN was defined as peak systolic BP >= 210 mmHg for men and >= 190 mmHg for women. RESULTS: We analyzed 65 patients (40 [61.5%] male; mean age at follow-up 30 +/- 8 years). Median age at AC repair was 7 years (P25-P75: 4-20) and mean follow-up was 20 +/- 7 years. Only one patient had diabetes and 10 (15.4%) had dyslipidemia. The majority of patients had controlled BP at rest and only nine (18%) were under antihypertensive medication. Forty-nine patients performed a treadmill exercise test. The mean duration of exercise was 10.7 +/- 3.1 minutes and mean peak heart rate was 166 +/- 18 beats per minute. Eleven (22%) patients had a hypertensive response, among whom only three (33%) had uncontrolled BP at rest. In our study treatment with angiotensin-converting enzyme inhibitors (ACEI) (OR 4.0 [95% CI 1.9-18.1]) and the peak instantaneous gradient in the descending aorta by TTE (OR 8.2 [95% CI 1.8-37.0]) were predictors of a hypertensive response with exercise. Age at surgery and type of AC repair were not associated with a hypertensive response on exercise. CONCLUSIONS: In this study we found a significant prevalence of exercise-induced HTN in adult patients after successful AC repair despite adequate BP control at rest. Exercise-induced HTN was significantly related to higher peak gradient in the descending aorta and treatment with ACEI. These results highlight the complexity of the adult AC population and show that, even after a good surgical result, several patients remain at high cardiovascular risk and require long-term follow-up. PMID- 24239396 TI - A rare case of persistent troponin elevation in a patient with chronic heart failure. AB - We present the case of a woman diagnosed with hypertrophic cardiomyopathy who suffered a myocardial infarction when she was 28 years old, without coronary artery disease on coronary angiography. Two years later, she presented signs of heart failure and left ventricular systolic dysfunction with persistent troponin I elevation, followed by progressive worsening of ventricular dysfunction. PMID- 24239398 TI - Reply: To PMID 23153766. PMID- 24239400 TI - Patient perception of quality online: a double edged sword. PMID- 24239397 TI - Histone deacetylase inhibitors decrease intra-abdominal adhesions with one intraoperative dose by reducing peritoneal fibrin deposition pathways. AB - BACKGROUND: We previously demonstrated that postoperative peritoneal injury and inflammation contribute to adhesiogenesis. Recent evidence suggests that in addition to their role of interfering with the acetylation status of nuclear histone proteins, histone deacetylase inhibitors (HDACIs) including valproic acid (VPA) can target nonhistone proteins to resolve inflammation and modulate immune cells. We hypothesized that HDACIs could reduce adhesions. METHODS: Seventy-two rats underwent laparotomy with creation of 6 peritoneal ischemic buttons to induce adhesions. A single intraperitoneal (IP) dose of 50 mg/kg VPA was administered intraoperatively, whereas controls received vehicle. To evaluate the timing, 25 rats underwent ischemic button creation with either an intraoperative or a delayed IP dose of VPA at 1, 3, or 6 hours postoperatively. On postoperative day 7, adhesions were quantified. To investigate mechanisms, ischemic buttons were created in 24 rats and either VPA or saline was administered in 1 intraoperative dose. At 3 or 24 hours later, peritoneal fluid was collected and fibrinolytic activity measured. Alternatively, button tissue was collected 30 minutes postoperatively to measure tissue factor, fibrinogen, and vascular endothelial growth factor (VEGF) by real-time polymerase chain reaction or Western blot. RESULTS: A single intraoperative dose of VPA reduced adhesions by 50% relative to controls (P < .001). Delayed dosing did not reduce adhesions. In operated animals, peritoneal fibrinolytic activity was not different between groups. Tissue factor mRNA was downregulated by 50% (P = .02) and protein by 34% (P < .01) in animals administered VPA versus saline. VPA decreased fibrinogen protein by 56% and VEGF protein by 25% compared with saline (P = .03). CONCLUSION: These findings suggest that VPA rapidly reduces the extravasation of key adhesiogenic substrates into the peritoneum. A single, intraoperative intervention provides an ideal dosing strategy and indicates an exciting new role for HDACIs in adhesion prevention. PMID- 24239401 TI - Adherence to dietary guidelines positively affects quality of life and functional status of older adults. AB - BACKGROUND: Nutritional parameters could influence self-perceived health and functional status of older adults. OBJECTIVE: We prospectively determined the association between diet quality and quality of life and activities of daily living. DESIGN: This was an observational cohort study in which total diet scores, reflecting adherence to dietary guidelines, were determined. Dietary intakes were assessed using a food frequency questionnaire at baseline. Total diet scores were allocated for intake of selected food groups and nutrients for each participant as described in the Australian Guide to Healthy Eating. Higher scores indicated closer adherence to dietary guidelines. PARTICIPANTS/SETTING: In Sydney, Australia, 1,305 and 895 participants (aged >= 55 years) with complete data were examined over 5 and 10 years, respectively. MAIN OUTCOME VARIABLES: The 36-Item Short-Form Survey assesses quality of life and has eight subscales representing dimensions of health and well-being; higher scores reflect better quality of life. Functional status was determined once at the 10-year follow-up by the Older Americans Resources and Services activities of daily living scale. This scale has 14 items: seven items assess basic activities of daily living (eg, eating and walking) and seven items assess instrumental activities of daily living (eg, shopping or housework). STATISTICAL ANALYSES PERFORMED: Normalized 36 Item Short-Form Survey component scores were used in analysis of covariance to calculate multivariable adjusted mean scores. Logistic regression analysis was used to calculate adjusted odds ratios and 95% CIs to demonstrate the association between total diet score with the 5-year incidence of impaired activities of daily living. RESULTS: Participants in the highest vs lowest quartile of baseline total diet scores had adjusted mean scores 5.6, 4.0, 5.3, and 2.6 units higher in these 36-Item Short-Form Survey domains 5 years later: physical function (P trend=0.003), general health (P trend=0.02), vitality (P trend=0.001), and physical composite score (P trend=0.003), respectively. Participants in the highest vs lowest quartile of baseline total diet scores had 50% reduced risk of impaired instrumental activites of daily living at follow-up (multivariable adjusted P trend=0.03). CONCLUSIONS: Higher diet quality was prospectively associated with better quality of life and functional ability. PMID- 24239402 TI - Colectomy for patients with ulcerative colitis and primary sclerosing cholangitis - what next? AB - BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) occurs in 2%-8% of patients who suffer from ulcerative colitis (UC). For patients who require colectomy, ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA) is employed to preserve continence.We evaluated the outcomes after IPAA and IRA for patients with UC-PSC, using patients with UC but without PSC as controls (UC-only group). PATIENTS: In a case-control study conducted at Sahlgrenska University Hospital, Sweden, patients with UC-PSC (N=48; 31 IPAA and 17 IRA) were compared to patients with UC only (N=113; 62 IPAA and 51 IRA). Functional outcomes (Oresland score), pouchitis, surgical complications, and failure were evaluated. RESULTS: For patients with IPAA, the median Oresland scores were similar for the two groups: 5 (range, 0-13) for the UC-PSC group and 5 for the UC-only group (range, 0-12; p>0.05). However, the IRA scores were significantly different at 7 (range, 2-11) and 3 (range, 0-11) for the respective groups (p=0.005). Pouchitis was more frequent in patients with UC-PSC. Complication rates did not differ. For patients with IPAA, the failure rate was 16% for those in the UC-PSC group versus 6% for those in the UC-only group (p>0.05); the corresponding results for IRA were 53% versus 22% (p=0.03). CONCLUSIONS: For cases of IPAA, pouchitis seems to be more common in patients with UC-PSC. However, the functional outcomes and failure rates are unaffected by concurrent PSC. For patients with UC-PSC, functional outcome is poor and the failure rate is high after IRA. PMID- 24239403 TI - A patient with severe Crohn's colitis responds to Faecal Microbiota Transplantation. PMID- 24239404 TI - The process of adult day service use. AB - The objective of this study was to examine why and how families and older adults utilize adult day services. The current study included three months of participant observation in one rural and one suburban adult day service program in an upper-Midwestern region of the United States as well as semi-structured interviews with 14 family members of clients and 12 staff members from these programs. Several key constructs emerged that organized the multiple sources of qualitative data including programmatic philosophy, positioning, and environment of ADS; clients' and family members' reasons for use; the process of ADS use by families and clients; and pathways to family/client psychosocial and client functional outcomes. A number of inter-related themes emerged within each construct. The constructs identified and their potential associations among each other were used to expand upon and refine prior conceptualizations of ADS to frame future clinical and research efforts. PMID- 24239405 TI - Amino ozonides exhibit in vitro activity against Echinococcus multilocularis metacestodes. AB - Artemisinin is an antimalarial sesquiterpene lactone that contains a 1,2,4 trioxane heterocycle. Dihydroartemisinin and artesunate demonstrated activity against Echinococcus multilocularis metacestodes in vitro but were not effective in a mouse model. In this study, the in vitro effects of a small library of synthetic ozonides (1,2,4-trioxolanes) were investigated. Initial compound screening against E. multilocularis metacestodes was performed at 20MUM, and selected ozonides were further assessed in dose-response studies in metacestode cultures and mammalian cells. Transmission electron microscopy (TEM) was employed to characterise compound-induced structural alterations. At 20MUM, the most potent ozonides (OZ401, OZ455, OZ491 and OZ494) led to death of ca. 60-100% of the parasites. Subsequent dose-response experiments demonstrated that OZ401, OZ455 and OZ491, which contain an aminopropylether substructure, were the most potent, with 50% inhibitory concentrations ranging from 11MUM to 14MUM. Cytotoxicity for these three ozonides, assessed in human foreskin fibroblasts, rat hepatoma cells and green monkey epithelial kidney (Vero) cells, was evident only at high concentrations. TEM demonstrated that OZ401 and OZ491 treatment induced considerable metabolic impairment in metacestodes at 1 day post exposure. At Day 3 post exposure, the germinal layer was severely distorted, although some intact cells were still visible, demonstrating that not all cell types in the parasite tissue were equally affected. Complete destruction of the germinal layer was noted at 5 days post exposure. Synthetic ozonides could represent interesting leads that will be further investigated in a suitable in vivo model of E. multilocularis infection. PMID- 24239406 TI - Extensively drug-resistant Pseudomonas aeruginosa ventriculitis and meningitis treated with intrathecal colistin. PMID- 24239407 TI - The effect of leg preference on postural stability in healthy athletes. AB - In research regarding postural stability, leg preference is often tested and controlled for. However, leg preference may vary between tasks. As athletes are a group of interest for postural stability testing, we evaluated the effect of five leg preference tasks categorization (step up, hop, ball kick, balance, pick up) on single-leg postural stability of 16 field hockey athletes. The 'center of pressure speed' was calculated as the primary outcome variable of single-leg postural stability. Secondary variables were 'mean length of the GRF vector in the horizontal plane', 'mean length of the ankle angular velocity vector', and 'mean length of the hip angular velocity vector', as well as the separate outcomes per degree of freedom. Results showed that leg preference was inconsistent between leg preference tasks. Moreover, the primary and secondary variables yielded no significant difference between the preferred and non preferred legs, regardless of the applied leg preference task categorization (p>0.05). The present findings do not support the usability of leg preference tasks in controlling for bias of postural stability. In conclusion, none of the applied leg preference tasks revealed a significant effect on postural stability in healthy field hockey athletes. PMID- 24239408 TI - [Patient adherence to oral anticoagulant treatment (warfarin)]. PMID- 24239409 TI - Critical dose and toxicity index of organs at risk in radiotherapy: analyzing the calculated effects of modified dose fractionation in non-small cell lung cancer. AB - To increase the efficacy of radiotherapy for non-small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new "toxicity index" (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V20 in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC. PMID- 24239410 TI - Triple-phase dynamic MRI: a new clue to predict malignant transformation of giant cell tumor of bone. AB - OBJECTIVE: Our purpose was, through the comparison of the characteristics of time intensity curve on triple-phase dynamic contrast-enhanced MRI among groups of giant cell tumor of bone (GCTB), recurrent benign giant cell tumor of bone (RBGCTB), and secondary malignant giant cell tumor of bone (SMGCTB), to find clues to predict the malignant transformation of GCTB. SUBJECTS AND METHODS: 21 patients diagnosed as GCTB were included in this study. All cases took recurrence after intralesional curettage. 9 cases were confirmed as SMGCTB and 12 cases were confirmed as RBGCTB. Cases were divided into four groups: group A, GCTB (n=9); group B, SMGCTB (n=9); group C, GCTB (n=12); group D, RBGCTB (n=12). Enhancement index(EI) of lesions on DCEMRI was calculated using formula: EI(t)=[S(t) S(0)]/S(0), where S(0) was signal intensity of lesion on non-contrast-enhanced T1 weighted images and S(t) was signal intensity of lesion on DCEMRI (t=30, 60, 180s). Enhancement index of each group in each phase was compared using One-Way ANOVA analysis. Slope values of time-intensity curve were compared by the same way. RESULTS: Time-intensity curve of SMGCTB was characterized by a steep upward slope followed by an early and rapid washout phase. Time-intensity curve of GCTB and RBGCTB was characterized by a steep slope followed by a relatively slow washout phase. No significant difference in enhancement index was found in the first phase (p>0.05). There was significant difference in the second and the third phase (p<0.05). Enhancement index of group B (SMGCTB) was smaller. There was no difference in rising slope value (p>0.05). CONCLUSIONS: Dynamic contrast enhanced MRI appears a helpful method to find new clues to predict malignant transformation of GCTB. PMID- 24239411 TI - Mechanical thrombectomy "as a rescue treatment" of thromboembolic complications during endovascular treatment of intracranial aneurysms. AB - Acute thromboembolic periprocedural events during endovascular intracranial aneurysm treatment are mostly treated with intravenous or intra-arterial pharmacological thrombolysis. The present report describes a case of mechanical thrombectomy as a rescue treatment that may be an acceptable alternative to the current strategies. The feasibility and safety of stent retrievers in such a clinical indication are also discussed. PMID- 24239412 TI - Clinical factors are significant predictors of outcome post intra-arterial therapy for acute ischaemic stroke: a review. AB - Intra-arterial therapy (IAT) provides superior recanalisation rates, approaching 80% for the current generation of endovascular devices. Furthermore, IAT may allow for an extended therapeutic window beyond that which is permissible for intravenous thrombolysis. However, the improved recanalisation rates are not matched by concordant clinical outcomes, leading to an invigorated search for predictors of clinical outcome. There is emerging evidence that younger age, mild moderate stroke, and shorter vessel occlusion time are associated with better clinical outcome after IAT. This review aims to critically appraise current evidence that may inform changes in the selective inclusion of clinical factors in the future design and trial of IAT. PMID- 24239413 TI - Reversible bilateral basal ganglia lesions related to Epstein-Barr virus encephalitis. PMID- 24239414 TI - Hair ethyl glucuronide levels as a marker for alcohol use and abuse: a review of the current state of the art. AB - BACKGROUND: Ethyl glucuronide (EtG) is a minor alcohol metabolite that has been proposed as a stable marker in hair to detect and quantify alcohol consumption over long time periods. METHODS: We provide an outline of currently available techniques for EtG hair sample analysis and highlight the pitfalls related to data interpretation. The literature of EtG analysis has been reviewed from January 1980 up to August 2013. In addition, we present an overview of the clinical and forensic studies which have used EtG quantification in hair as a marker for alcohol consumption/abstinence and we provide suggestions for future research. RESULTS: EtG is a stable marker in hair that can be used to detect and quantify alcohol consumption over long time periods. This alcohol metabolite remains in hair after complete elimination of alcohol. Currently, there are three main analytical techniques used to quantify EtG in hair: gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). No standardized protocols are yet available for the analysis of EtG levels in hair samples, and the current protocols vary in sample preparation and extraction procedures. Variables such as hair length, cosmetic treatment, gender, and pathophysiological conditions influence the final results and should be taken into account. CONCLUSIONS: EtG quantification in hair is a useful tool for the objective detection of alcohol consumption over extended time periods, but care should be taken when interpreting the results. PMID- 24239415 TI - The fabrication of aspherical microlenses using focused ion-beam techniques. AB - Aspheric lenses are the most common method for correcting for spherical aberrations but, in microlens production, highly-controlled lens profiles are hard to achieve. We demonstrate a technique for creating bespoke, highly-accurate aspheric or spherical profile silicon microlens moulds, of almost any footprint, using focused ion-beam milling. Along with this, we present a method of removing induced ion-beam damage in silicon, via a hydrofluoric acid etch, helping to recover the surface's optical and chemical properties. In this paper, we demonstrate that our milled and etched moulds have a roughness of 4.0-4.1 nm, meaning they scatter less than 1% of light, down to wavelengths of 51 nm, showing that the moulds are suitable to make lenses that are able to handle light from UV up to infra-red. Using empirical experiments and computer simulations, we show that increasing the ion-dose when milling increases the amount of gallium a hydrofluoric acid etch can remove, by increasing the degree of amorphisation within the surface. For doses above 3000 MUC/cm(2) this restores previous surface properties, reducing adhesion to the mould, allowing for a cleaner release and enabling higher quality lenses to be made. Our technique is used to make aspheric microlenses of down to 3 MUm in size, but with a potential to make lenses smaller than 1 MUm. PMID- 24239416 TI - Towards full-resolution inline electron holography. AB - With the availability of fast computers, inline electron holography, a technique for reconstructing both amplitude and phase of the electron wave function as scattered by the sample from a set of differently aberrated transmission electron microscopy images, is becoming increasingly quantitative. While focal series reconstruction from transmission electron microscopy images has already been practiced for at least 3 decades, existing approaches can only recover a relatively small band of spatial frequencies. Here I present a reconstruction scheme which is capable of reconstructing the electron wave function for a very large range of spatial frequencies, demonstrating its performance using simulated as well as experimental data. PMID- 24239417 TI - Immune cell response to Candida cell wall mannan derived branched alpha oligomannoside conjugates in mice. AB - BACKGROUND: Constructs composed of cell wall mannan-derived moieties conjugated to immunogenic proteins could be promising agents for induction of protective anti-Candida immune responses. METHODS: This report is focused on the cellular immune response differences induced by BSA-based conjugates bearing synthetic alpha-1,6-branched oligomannosides. For monitoring of the immune responses following active immunization we evaluated changes in the frequencies of T and B lymphocytes and their activation status in the blood and spleen. We compared the immunization-induced changes of co-stimulatory molecules CD80 and CD86 expression on blood neutrophils and Th1/Th2 polarization of the immune response based on IFN gamma, TNF-alpha (pro-Th1), IL-4, and IL-10 (pro-Th2) cytokines levels and induction of IL-17. RESULTS: The results pointed out a comparable effect of the conjugates on the modulation of T and B lymphocytes frequencies in blood and spleen. Both conjugates induced upregulation of CD25 surface antigen on CD4(+) T lymphocytes, independently on the structural differences of oligosaccharides. The differences in structure of oligomannoside antigens or conjugate constructs were reflected in the increase of co-stimulatory molecules CD80 and CD86 expression on neutrophils, and in induced cytokine response. M5-BSA conjugate induced only a slight increase in CD80 expression but a significant increase in IFN-gamma, TNF alpha, and IL-10. M6-BSA conjugate induced a significant increase of CD80 expression and increase of TNF-alpha, IL-4, and IL-10. CONCLUSION: Obtained data demonstrate the importance of cellular immune response analysis for investigation of immunomodulatory properties of oligomannoside-protein conjugates. PMID- 24239418 TI - Reply by authors. PMID- 24239419 TI - Re: clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies: M. Gelbard, I. Goldstein, W. J. Hellstrom, C. G. McMahon, T. Smith, J. Tursi, N. Jones, G. J. Kaufman and C. C. Carson, III J Urol 2013; 190: 199-207. PMID- 24239420 TI - Reply by authors. PMID- 24239421 TI - Re: impact of smoking status on bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: M. Hagiwara, E. Kikuchi, N. Tanaka, K. Matsumoto, H. Ide, A. Miyajima, T. Masuda, S. Nakamura and M. Oya J Urol 2013; 189: 2062-2068. PMID- 24239422 TI - Should urinary diversion for bladder pain syndrome/interstitial cystitis include cystectomy? No. PMID- 24239423 TI - Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection. AB - BACKGROUND: Dengue virus (DENV) infection remains a major public health burden worldwide. Soluble mediators may play a critical role in the pathogenesis of acute DENV infection. Galectin-9 (Gal-9) is a soluble beta-galactoside-binding lectin, with multiple immunoregulatory and inflammatory properties. OBJECTIVE: To investigate plasma Gal-9 levels as a biomarker for DENV infection. STUDY DESIGN: We enrolled 65 DENV infected patients during the 2010 epidemic in the Philippines and measured their plasma Gal-9 and cytokine/chemokine levels, DENV genotypes, and copy number during the critical and recovery phases of illness. RESULTS: During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to healthy or those with non-dengue febrile illness. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464 pg/ml; dengue fever patients (DF): 1407 pg/ml; non-dengue febrile illness: 616 pg/ml; healthy: 196 pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in DF and DHF patients. Gal-9 levels tracked viral load, and were associated with multiple cytokines and chemokines (IL-1alpha, IL-8, IP-10, and VEGF), including monocyte frequencies and hematologic variables of coagulation. Further discriminant analyses showed that eotaxin, Gal-9, IFN-alpha2, and MCP-1 could detect 92% of DHF and 79.3% of DF, specifically (P<0.01). CONCLUSION: Gal-9 appears to track DENV inflammatory responses, and therefore, it could serve as an important novel biomarker of acute DENV infection and disease severity. PMID- 24239424 TI - Is there a relation between AOFAS ankle-hindfoot score and SF-36 in evaluation of Achilles ruptures treated by percutaneous technique? AB - The percutaneous technique of Achilles tendon repair seems to offer satisfactory clinical and functional results, although these results have been evaluated mainly using objective rating scales. Recently, some "subjective" rating scales have been combined to evaluate the results of various surgical treatments. The purpose of the present study was to compare the results of a percutaneous Achilles tendon repair evaluated objectively using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and subjectively using the Medical Outcomes Study, short-form, 36-item questionnaire (SF-36) questionnaire. A total of 17 consecutive patients were treated for acute Achilles tendon rupture using the modified percutaneous Ma and Griffith technique. We reviewed all patients with a follow-up of 24 to 64 months (mean 45.5). At the final follow-up visit, the AOFAS ankle-hindfoot score of each patient was compared with each 1 of the 8 domains of the SF-36 questionnaire, using the parametric Pearson correlation coefficient and the equivalent nonparametric Spearman rho correlation coefficient. The relation between the objective (AOFAS) and subjective (SF-36) results showed a significant correlation (Pearson's correlation coefficient) between the physical functioning (r = 0.597, p = .011) and bodily pain (r = 0.663, p = .004) SF-36 domains, and a nonstatistically significant correlation with the other SF-36 domains. Very similar results were found using the nonparametric Spearman rho correlation coefficient. These results suggest that regarding pain and function, the AOFAS ankle-hindfoot score and SF-36 provide complementary information; therefore, we believe that the SF-36 questionnaire should be used with the AOFAS ankle-hindfoot score for a more complete evaluation of the outcome. PMID- 24239425 TI - First tarsometatarsal joint derotational arthrodesis--a new operative technique for flexible hallux valgus without touching the first metatarsophalangeal joint. AB - No operative technique for hallux valgus has been introduced in which the first metatarsophalangeal joint is not touched. We report the first tarsometatarsal joint derotational arthrodesis in which we mimic the function of the peroneus longus tendon without involving the first metatarsophalangeal joint, allowing function of the windlass mechanism without interference. We treated 66 patients (62 women and 4 men) with 84 flexible hallux valgus feet using our new operative technique. Preoperative and postoperative follow-up weightbearing radiographs were evaluated. Most patients had a pronation type foot (78%) preoperatively, and mean correction in hallux valgus and intermetatarsal angle was 20 degrees and 9 degrees , respectively (p < .001). The LaPorta classification showed a median change of 2.5 U (p < .001). We have described a new operative technique for flexible hallux valgus. The first tarsometatarsal joint derotational arthrodesis showed notable correction angles in hallux valgus, although the first metatarsophalangeal joint was left intact. PMID- 24239426 TI - Ultrasound-guided needle localization to aid foreign body removal in pediatric patients. AB - Patients with podiatric foreign body injury commonly present to the emergency department. Often, the foreign object cannot be easily located or removed, and radiographs are frequently obtained to aid in localization. In cases requiring tissue dissection to remove the foreign bodies, accurate localization is required for safe removal of small and difficult to visualize bodies. We present 2 pediatric cases in which an ultrasound-guided needle localization technique was used to facilitate successful removal of small, difficult to visualize foreign bodies from the plantar foot. Ultrasound-guided needle localization reduced the required incision length and depth and helped to minimize the risk of damage to surrounding tissue. PMID- 24239427 TI - Isolated talonavicular arthrodesis for talonavicular arthritis: a follow-up study. AB - We have reviewed a single surgeon's (M.S.) experience of talonavicular arthrodesis in 7 feet in 7 patients with isolated talonavicular arthritis. A standard dorsomedial approach was used to the talonavicular joint. Fixation was performed with 5.5-mm, partially threaded, cancellous screws. The visual analog scale for the foot and ankle (VASFA) was used to measure the preoperative and postoperative results in the categories of pain, function, other complaints, and total score. The follow-up period was 17 to 90 months (mean 48). The overall VASFA score ranged from +19.2 to +57.6 (mean +33.2, p < .01). The VASFA score for pain ranged from +19 to +74.8 (mean +51.3, p < .01). The VASFA score for function ranged from +12.5 to +68.2 (mean +28.3, p < .01). The VASFA score for other problems ranged from +12 to +45.8 (mean +25.5, p < .01). None of the 7 feet required revision, and all 7 patients were satisfied with the outcome and would have the operation again. We have concluded that, taking into account the small power of the present study, talonavicular arthrodesis is a successful treatment for isolated talonavicular arthritis. PMID- 24239428 TI - Can foot and ankle surgeons accurately estimate patient body mass index? AB - The body mass index (BMI) is an objective patient finding that has been established to have a negative effect on the development and outcomes of podiatric pathologic entities and interventions. The objective of the present investigation was to assess the ability of podiatric physicians to estimate the patient BMI from clinical and radiographic observation. For the clinical estimation of the patient BMI, podiatric specialists across 3 levels of experience (i.e., students, residents, and practicing clinicians) performed 294 estimations on 72 patients in 3 clinical situations (standing, sitting in a treatment chair, and lying in a hospital bed). It was more common to inaccurately estimate the patient BMI (77.9%) than it was to correctly estimate it (22.1%), with underestimations being the most common error (48.3%). The estimations were particularly inaccurate when the patients were in the common clinical situation of sitting in a treatment chair or lying in a hospital bed and with patients actually classified as obese. For the radiographic estimation of patient BMI, 150 consecutive lateral ankle radiographs were analyzed, with the ratio of the overlying soft tissue diameter to the underlying bone diameter calculated and compared. Positive, but weak, relationships were observed with these ratios. From these data, we have concluded that podiatric practitioners should perform an actual calculation of the patient BMI during the patient examination and medical decision-making process to fully appreciate the potential risks inherent to the treatment of obese patients. PMID- 24239429 TI - Technique for utilization of an interference screw for split peroneus brevis tendon transfer in lateral ankle stabilization. AB - We present a technique for split peroneous brevis lateral ankle stabilization using an interference screw as the fixation device. The interference screw provided stable fixation by way of physiologic tension and restored lateral ankle instability while preserving the range of motion in the surrounding joints. PMID- 24239430 TI - Immediate ketamine treatment does not prevent posttraumatic stress responses in an animal model for PTSD. AB - Clinical studies suggest that administration of ketamine hydrochloride-an antagonist at the N-methyl-d-aspartate ionophore-provides short-term amelioration for depressive symptoms. The effects of a brief course of ketamine given immediately following exposure to psychogenic stress on the behavioral stress responses were assessed in an animal model of posttraumatic stress disorder. Animals exposed to stress were treated 1h later with ketamine (0.5, 5, and 15 mg/kg) or vehicle for three days (N = 107). Outcome measures included behavior in the elevated plus maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into "extreme," "minimal," or "partial" behavioral response for analysis of prevalence rates of "PTSD-like behavior." Circulating corticosterone levels were assessed 20 min after injection of ketamine in exposed and unexposed animals (N = 62). The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Prevalence rates of extremely-, partially-, or minimally-disrupted behavior demonstrated that ketamine administered immediately following stress exposure was ineffective in alleviating "PTSD-like behavior" at day 30 after exposure. Administration of ketamine was associated with increase in freezing behavior after exposure to a trauma-cue on day 31. Corticosterone levels were significantly suppressed by ketamine only in the exposed animals. Administration of ketamine immediately following trauma-exposure may not only be ineffective but actually detrimental in the long term. A disruption of the post-stress HPA-response has been raised as a contributing factor. PMID- 24239432 TI - The evolution of epilepsy theory and practice at the National Hospital for the Relief and Cure of Epilepsy, Queen Square between 1860 and 1910. AB - In the years between 1860 and 1910, a revolution in epilepsy theory and practice occurred. The National Hospital for the Relief and Cure of the Paralysed and the Epileptic at Queen Square in London was at the center of this revolution. A series of remarkable physicians and surgeons were appointed to the staff. The four greatest were John Hughlings Jackson, Sir David Ferrier, Sir Victor Horsley, and Sir William Gowers. Their lasting contribution to epilepsy is discussed. Other physicians who made notable contributions to epilepsy were Jabez Spence Ramskill, Charles Eduard Brown-Sequard, Charles Bland Radcliffe, Sir John Russell Reynolds, Sir Edward Henry Sieveking, Walter Stacy Colman, and William Aldren Turner. At the hospital in this period, amongst the lasting contributions to epilepsy were the following: the development of a new conceptual basis of epilepsy, the development of a theory of the physiological structure of the nervous system in relation to epilepsy, the demonstration and investigation of cortical localization of epileptic activity, the establishment of the principle of focal epilepsy and the description of focal seizure types, the discovery of the first effective drug treatment for epilepsy (bromide therapy, indeed one of the first effective drug treatments in the whole of neurology), and the performance of the first surgical operation for epilepsy. This paper is based on the 2013 Gowers Memorial Lecture, delivered in May 2013. PMID- 24239431 TI - Bupropion response on sleep quality in patients with depression: implications for increased cardiovascular disease risk. AB - Depression could be an independent risk factor for cardiovascular disease. We assessed bupropion response in depressed patients by polysomnography (PSG) and cardiopulmonary coupling (CPC) variables. Nineteen subjects participated in a two session, two consecutive night PSG protocol. Participants received either placebo or bupropion-SR 150 mg, orally, in a randomized, double-blind cross-over fashion on night two. Outcome variables were: sleep stages, REM latency, stable, unstable sleep and very low frequency coupling (VLFC). CPC analysis uses heart rate variability and the electrocardiogram's R-wave amplitude fluctuations associated with respiration to generate frequency maps. Bupropion increased REM latency (p=0.043) but did not impact PSG sleep continuity, architecture and CPC variables. A trend (p=0.092) was observed towards increasing VLFC duration. Bupropion increased the number of stable-unstable sleep transitions (p=0.036). Moderate to strong correlations between PSG and CPC variables were found on placebo and bupropion nights. Limitations include a small sample size, limited power to detect CPC changes and lack of normal controls for comparison. Increased stable-unstable sleep transitions and VLFC duration may indicate vulnerability to cardiovascular disease due to their association with low heart rate variability that has been associated with increased mortality raising the question whether the beneficial effects of the antidepressant medication outweighs the impact on cardiopulmonary dynamics. PMID- 24239433 TI - Are children affected by epileptic neuropsychiatric comorbidities? AB - Childhood-onset epilepsy is associated with psychiatric and cognitive difficulties and with poor social outcomes in adulthood. Some antiepileptic drugs adversely affect behavior in susceptible children with easy-to-control or refractory epilepsies, contributing to a high risk of psychological and psychiatric disturbance. Studies had demonstrated that patients with benign rolandic epilepsy and absence epilepsy had more aggressive behavior, depression, and anxiety disorders than control children. Psychiatric comorbidities are strongly associated with a poor long-term health-related quality of life in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and long-term treatment for these conditions, even if seizures remit. PMID- 24239434 TI - Understanding the perceived treatment needs of patients with psychogenic nonepileptic seizures. AB - Psychological therapy is generally considered the treatment of choice for psychogenic nonepileptic seizures (PNES), but there is a paucity of research on patients' attitudes towards psychological referral. We conducted semistructured interviews with twelve patients with PNES awaiting psychological treatment in order to understand their perceived treatment needs. Data were analyzed inductively according to the principles of thematic analysis. The results indicated that our patients had clear ideas about their treatment needs and a desire to recover by 'returning to normality'. Many participants felt 'caught in limbo' following their PNES diagnosis, however, because of uncertainties about their condition and a lack of support from professionals. This linked with participants feeling unsure whether psychological treatment would meet their needs; there was also apprehension for some participants about the potential negative consequences of therapy. The clinical implications of these findings are discussed, and recommendations for future research are made. PMID- 24239436 TI - Cognitive decline is mediated by gray matter changes during middle age. AB - The present theoretical framework of Alzheimer's disease proposes that pathophysiological changes occur 10-20 years before the diagnosis of dementia. We addressed the question of how age-related changes in gray matter mediate the cognitive performance during middle age. Eighty-two participants (40-50 years, +/ 2) were assessed with a comprehensive neuropsychological battery covering a broad spectrum of cognitive domains and components. Mediation effects were studied with hierarchical regression and bootstrapping analysis. Results showed that more vulnerable cognitive components were related to executive functioning and in a lesser degree to processing speed. Age-related differences in gray matter mainly involved the frontal lobes. Moreover, age-related differences in visuoconstructive, visuospatial functions, reaction time, and mental flexibility and executive control were mediated by several gray matter regions. It is important to increase the knowledge of the impact of brain changes on cognitive function during middle age. To define the early stages of the aging process may allow early detection of pathologic changes and therapeutic interventions. PMID- 24239435 TI - Healthcare utilization and costs in adults with stable and uncontrolled epilepsy. AB - Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had >=1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and/or underidentification of utilization may substantially contribute to costs. PMID- 24239437 TI - Vitamin D receptor genetic variants and Parkinson's disease in a Taiwanese population. AB - Patients with Parkinson's disease (PD) have hypovitaminosis D status and genetic variants of vitamin D receptor (VDR) gene are recently shown to be associated with PD in a large-scale genome-wide association study in a Caucasian population. Few studies examined VDR genetic variants in large-scale Asian patients with PD. We therefore genotyped 6 VDR genetic variants in a total of 1492 Taiwanese subjects, including 700 patients with PD and 792 age and/or gender matched control subjects. We did not observe any significant associations between the studied genetic variants of VDR and the risk of PD. Our data suggest that genetic variations of the VDR gene did not play a major role in a Taiwanese PD population. Further studies of VDR and its interaction with serum vitamin D levels are warranted to clarify the potential role of vitamin D in PD pathogenesis. PMID- 24239438 TI - How age-related strategy switching deficits affect wayfinding in complex environments. AB - Although most research on navigation in aging focuses on allocentric processing deficits, impaired strategy switching may also contribute to navigational decline. Using a specifically designed task involving navigating a town-like virtual environment, we assessed the ability of young and old participants to switch from following learned routes to finding novel shortcuts. We found large age differences in the length of routes taken during testing and in use of shortcuts, as, while nearly all young participants switched from the egocentric route-following strategy to the allocentric wayfinding strategy, none of the older participants stably switched. Although secondary tasks confirmed that older participants were impaired both at strategy switching and allocentric processing, the difficulty in using shortcuts was selectively related to impaired strategy switching. This may in turn relate to dysfunction of the prefrontal-noradrenergic network responsible for coordinating switching behavior. We conclude that the large age difference in performance at the shortcutting task demonstrates for the first time, how strategy switching deficits can have a severe impact on navigation in aging. PMID- 24239439 TI - Multi-residue method for the detection of veterinary drugs in distillers grains by liquid chromatography-Orbitrap high resolution mass spectrometry. AB - Distillers Grain (DG) is an important by-product of ethanol production. The ethanol production process uses only the starch portion of the plant and all the remaining nutrients, protein, fat, minerals, and vitamins remain in DGs, a valuable feed material for livestock. The use of antimicrobial drugs is helpful to limit harmful bacterial growth during the early part of the fermentation process. This can lead to the possible presence of contaminants in the by products that are used in the food and feed industries, resulting in a major concern for the development of bacterial resistance in both humans and animals. To facilitate the detection of antimicrobial and other commonly used veterinary drugs in DGs, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed targeting a wide range of 12 chemical classes of anti bacterial substances and drugs, such as ionophore and non-ionophore authorized coccidiostats, banned coccidiostats, macrolides, tetracyclines, nitroimidazoles, amphenicols, quinolones, sulphonamides, tranquilizers, non-steroidal anti inflammatory drugs and benzimidazoles. Following a simple and fast extraction step with a mixture of organic solvents, the extract was directly injected into the LC coupled to an Orbitrap mass analyzer. The identification of residues is based on accurate mass measurement. The high mass resolution of 50,000 full width at half maximum (FWHM) and corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in such a complex matrix. A single-laboratory validation procedure was carried out evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance for precision and trueness, and allowed the determination of the compounds at low concentration. The proposed multi-method demonstrated that liquid chromatography coupled to an Orbitrap mass spectrometer is a promising analytical technique, suitable for official residue control of a variety of veterinary drugs in DGs supporting feed safety policies. PMID- 24239440 TI - King of hearts for ace of spades: apical hypertrophic cardiomyopathy. PMID- 24239441 TI - Underuse of vena cava filters in unstable patients with acute pulmonary embolism. PMID- 24239442 TI - Autonomic denervation and Western diseases. PMID- 24239443 TI - A meta-analysis and scoping review of social cognition performance in social phobia, posttraumatic stress disorder and other anxiety disorders. AB - Social cognition deficits are observed in a variety of psychiatric illnesses. However, data concerning anxiety disorders are sparse and difficult to interpret. This meta-analysis aims at determining if social cognition is affected in social phobia (SP) or posttraumatic stress disorder (PTSD) compared to non-clinical controls and the specificity of such deficits relatively to other anxiety disorders. The scoping review aims to identify research gaps in the field. Forty studies assessing mentalizing, emotion recognition, social perception/knowledge or attributional style in anxiety disorders were included, totalizing 1417 anxious patients and 1321 non-clinical controls. Results indicate distinct patterns of social cognition impairments: people with PTSD show deficits in mentalizing (effect size d = -1.13) and emotion recognition (d = -1.6) while other anxiety disorders including SP showed attributional biases (d = -0.53 to d = -1.15). The scoping review identified several under investigated domains of social cognition in anxiety disorders. Some recommendations are expressed for future studies to explore the full range of social cognition in anxiety disorders and allow direct comparisons between different disorders. PMID- 24239444 TI - Techniques, indications and complications of corneal debridement. AB - The cornea is the most exposed surface of the eye and, as such, is vulnerable to external trauma and the risk of infection. Many corneal diseases alter shape, surface, and transparency and thus result in reduced vision. The external position of the cornea, however, lends itself to diagnostic and therapeutic maneuvers that are commonly performed and readily done in the clinic. More sophisticated techniques require the use of complex equipment such as excimer and femtosecond laser. Complications that develop from poor healing and/or secondary infection are best avoided with appropriate technique, antisepsis, and modification of wound healing. We review corneal debridement in the management of corneal disease. PMID- 24239446 TI - An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders. AB - CONTEXT: Botulinum toxin A (BoNTA) has received regulatory approval for use in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), but it remains unlicensed in other lower urinary tract symptoms (LUTS) indications such as nonneurogenic LUTS in men with benign prostatic enlargement (LUTS/BPE), bladder pain syndrome (BPS), and detrusor sphincter dyssynergia (DSD). OBJECTIVE: To compare statistically the outcomes of high level of evidence (LE) studies with placebo using BoNTA for LUTS indications; NDO, OAB, LUTS/BPE, BPS and DSD. EVIDENCE ACQUISITION: We conducted a systematic review of the published literature on PubMed, Scopus, and Embase reporting on BoNTA use in LUTS dysfunction. Statistical comparison was made between high LE studies with placebo and low LE studies. EVIDENCE SYNTHESIS: In adult NDO, there are significantly greater improvements with BoNTA in daily incontinence and catheterisation episodes (-63% and -18%, respectively; p<0.01), and the urodynamic parameters of maximum cystometric capacity (MCC), reflex volume, and maximum detrusor pressure (MDP) (68%, 61%, and -42%, respectively; all p<0.01). In OAB, BoNTA leads to significant improvements in bladder diary parameters such as daily frequency ( 29%), daily urgency (-38%), and daily incontinence (-59%) (all p<0.02). The urodynamic parameters of MCC and MDP improved by 58% (p=0.04) and -29% (p=0.002), respectively. The risk of urinary tract infection was significantly increased from placebo at 21% versus 7% (p<0.001), respectively; the risk of intermittent self-catherisation increased from 0% to 12% (p<0.001). Men with LUTS/BPE showed no significant improvements in International Prostate Symptom Score, maximum flow rate, or prostate volume. There were insufficient data for statistical analysis in DSD, BPS, and paediatric studies. Low LE studies were found to overestimate the effects of BoNTA in all indications, but differences from high LE studies were significant in only a few parameters. CONCLUSIONS: BoNTA significantly improves all symptoms and urodynamic parameters in NDO and OAB. The effect of BoNTA in treating LUTS dysfunction appears to be overestimated in lower as opposed to higher LE studies. PMID- 24239445 TI - Risk factors for restricting back pain in older persons. AB - OBJECTIVES: To identify risk factors for back pain leading to restricted activity (restricting back pain) in older persons. DESIGN: Prospective cohort study. SETTING: Greater New Haven, Connecticut. PARTICIPANTS: A total of 731 men and women aged 70 years or older, who were community living and nondisabled in essential activities of daily living at baseline. MEASUREMENTS: Candidate risk factors were ascertained every 18 months for 108 months during comprehensive home based assessments. Restricting back pain was assessed during monthly telephone interviews for up to 126 months. Incident episodes of (1) short-term (1 episode lasting 1 month) restricting back pain; and (2) persistent (1 episode lasting 2 or more months) or recurrent (2 or more episodes of any duration) restricting back pain were determined during each 18-month interval. The associations between the candidate risk factors and short-term and persistent/recurrent restricting back pain, respectively, were evaluated using a multivariable Cox model. RESULTS: The cumulative incidence was 21.3% (95% confidence interval [CI] 19.6%-23.1%) for short-term restricting back pain and 20.6% (CI 18.6%-22.9%) for persistent/recurrent restricting back pain over a median follow-up of 109 months. In a recurrent event multivariable analysis, female sex (hazard ratio [HR] 1.30; 1.07-1.58), weak grip strength (HR 1.24; 1.01-1.52), and hip weakness (HR 1.19; 1.07-1.32) were independently associated with an increased likelihood of having short-term restricting back pain, whereas female sex (HR 1.48; CI 1.13-1.94), depressive symptoms (HR 1.57; 1.23-2.00), 2 or more chronic conditions (HR 1.38; 1.08-1.77), and arthritis (HR 1.66; 1.31-2.09) were independently associated with persistent/recurrent restricting back pain. CONCLUSION: In this prospective study, several factors were independently associated with restricting back pain, including some that may be modifiable and therefore potential targets for interventions to reduce this common and often recurrent condition in older persons. PMID- 24239447 TI - The role of response evaluation criteria in solid tumour in anticancer treatment evaluation: results of a survey in the oncology community. AB - PURPOSE: With the increasing use of novel targeted agents and the development of high imaging techniques, response evaluation criteria in solid tumour (RECIST) 1.1 developed primarily for cytotoxic agents and anatomic imaging, has demonstrated limitations. A survey was conducted of RECIST users to identify concerns and their suggestions for future RECIST criteria. METHODS: 140 key partners of the RECIST collaboration were asked to complete a questionnaire. The 49 questions concerned (a) satisfaction and concerns with RECIST 1.1; (b) use of modified RECIST criteria and (c) suggestions for the next RECIST Version. RESULTS: Sixty-five replies were received. 52.3% responders were satisfied with RECIST 1.1, while 10.8% indicated dissatisfaction. Areas of potential weakness included: (a) lack of incorporation of potential early indicators of response such as functional imaging, (b) lack of validation in rarer tumour types and (c) lack of validation for novel (targeted) agents. Suggestions were multiple, with highest numbers on two points: developing sub-criteria for certain disease types and including advanced imaging techniques for the evaluation. CONCLUSIONS: Constructive suggestions were received for optimising the next version. Ongoing data collection will make it possible to investigate the possible utilisation of fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in tumour assessment, to verify whether RECIST is/can still be applicable in novel targeted therapy and to consider the need for criteria for specific disease types. PMID- 24239448 TI - A basis for translational cancer research on aetiology, pathogenesis and prognosis: Guideline for standardised and population-based linkages of biobanks to cancer registries. AB - Population-based cancer research is paramount for controlling cancer. Cancer research is increasingly dependent on access to biospecimens from subjects that have been followed-up for future health outcomes. This is achieved using longitudinal follow-up of cohorts and biobanks using cancer registry linkages. All over the world, more and more large population-based cohorts and advanced biobanking facilities are established. International standardisation and networking in the linkage of cohorts and biobanks to cancer registries is required in order to enable international cancer research and comparability of research results. An international operating procedure and standard minimum dataset for linkages of biobanks, cohorts and cancer registries is proposed. An internationally comparable provision of well characterised study bases for molecular cancer research will be an essential prerequisite for the success of translational medicine. PMID- 24239449 TI - Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma. AB - INTRODUCTION: Sequential use of targeted therapy (TT) has improved overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC). The value of objective response (OR) as compared to stable disease (SD) is unclear. We aimed to investigate OR of first-line TT and its impact on OS. MATERIAL AND METHODS: Retrospective analysis of OS among 331 mRCC patients with a first-line assessment according to RECIST 1.0. Characteristics between objective responders (complete response [CR] or partial remission [PR]), patients with SD and non responders (progressive disease [PD] and toxicity [Tox]) were compared with the Chi-square test and the Kruskal-Wallis test. Kaplan-Meier analysis of OS and progression-free survival (PFS). Cox model analysis of Predictors of OS . RESULTS: Best response was CR, PR, SD, PD and Tox in 9 (2.7%), 61 (18.4%), 167 (50.5%), 80 (24.2%) and 14 (4.2%) patients respectively resulting in an OR rate of 21%. Median OS in months: CR 63.2; PR 37.6; SD 35.9; PD 14.6; TOX 22.5 (p<0.0001). Median PFS for responders was 14.8, 11.5 for patients with SD and 2.5 for non-responders (p<0.0001). Similarly median OS was 38.7, 35.9 and 15.5 (p<0.00001). Primary resistance and a first-line PFS <6months were the strongest independent predictors of OS. The achievement of OR as compared to SD did not impact OS. CONCLUSIONS: In our cohort of unselected patients OR was not associated with superior OS as compared to SD. PMID- 24239450 TI - Lumbar myositis associated with Toxocara spp. infection. PMID- 24239451 TI - Changes in vertebral artery blood flow following various head positions and cervical spine manipulation. AB - OBJECTIVE: The objective of the study was to investigate the cerebrovascular hemodynamic response of cervical spine positions including rotation and cervical spine manipulation in vivo using magnetic resonance imaging technology on the vertebral artery (VA). METHODS: This pilot study was conducted as a blinded examiner cohort with 4 randomized clinical tasks. Ten healthy male participants aged 24 to 30 years (mean, 26.8 years) volunteered to participate in the study. None of the participants had a history of disabling neck, arm, or headache pain within the last 6 months. They did not have any current or history of neurologic symptoms. In a neutral head position, physiologic measures of VA blood flow and velocity at the C1-2 spinal level were obtained using phase-contrast magnetic resonance imaging after 3 different head positions and a chiropractic upper cervical spinal manipulation. A total of 30 flow-encoded phase-contrast images were collected over the cardiac cycle, in each of the 4 conditions, and were used to provide a blood flow profile for one complete cardiac cycle. Differences between flow (in milliliters per second) and velocity (in centimeters per second) variables were evaluated using repeated-measures analysis of variance. RESULTS: The side-to-side difference between ipsilateral and contralateral VA velocities was not significant for either velocities (P = .14) or flows (P = .19) throughout the conditions. There were no other interactions or trends toward a difference for any of the other blood flow or velocity variables. CONCLUSIONS: There were no significant changes in blood flow or velocity in the vertebral arteries of healthy young male adults after various head positions and cervical spine manipulations. PMID- 24239452 TI - Task specific grip force control in writer's cramp. AB - OBJECTIVE: Writer's cramp is defined as a task specific focal dystonia generating hypertonic muscle co-contractions during handwriting resulting in impaired writing performance and exaggerated finger force. However, little is known about the generalisation of grip force across tasks others than writing. The aim of the study was to directly compare regulation of grip forces during handwriting with force regulation in other fine-motor tasks in patients and control subjects. METHODS: Handwriting, lifting and cyclic movements of a grasped object were investigated in 21 patients and 14 controls. The applied forces were registered in all three tasks and compared between groups and tasks. In addition, task specific measures of fine-motor skill were assessed. RESULTS: As expected, patients generated exaggerated forces during handwriting compared to control subjects. However there were no statistically significant group differences during lifting and cyclic movements. The control group revealed a generalisation of grip forces across manual tasks whereas in patients there was no such correlation. CONCLUSION: We conclude that increased finger forces during handwriting are a task-specific phenomenon that does not necessarily generalise to other fine-motor tasks. SIGNIFICANCE: Force control of patients with writer's cramp in handwriting and other fine-motor tasks is characterised by individualised control strategies. PMID- 24239453 TI - Nerve ultrasound in diabetic polyneuropathy: the new frontier? PMID- 24239454 TI - The significance of significance: Overstating in the setting of many comparisons. PMID- 24239455 TI - Spectral analysis of the sleep onset period in primary insomnia. AB - OBJECTIVE: To compare the EEG power spectra characteristics of the sleep onset period (SOP) in patients with sleep onset insomnia (SOI), sleep maintenance insomnia (SMI) and good sleepers (GS). METHODS: The time course of EEG power density (1-40Hz) during the SOP was examined in thirty subjects (SOI patients: N=10, SMI patients: N=10, GS: N=10). RESULTS: The EEG power of the beta2 frequency band (18-29.75 Hz) was significantly lower in SOI than in SMI in the period preceding sleep onset. The alpha power was significantly higher for the SMI group compared to GS before sleep onset. Despite the lack of statistical significance, several differences in EEG dynamics were observed in SOI compared to two other groups: delta power increased slower after sleep onset; beta2 and 3 (18-29.75 and 30-39.75 Hz) power decrease less abruptly before sleep onset; beta1 (15-17.75 Hz) power increase through the whole SOP. CONCLUSIONS: The lower level of beta2 frequency band in SOI and the differences in dynamics in delta and beta bands may suggest that a mechanism other than hyperarousal participates in etiology of SOI. SIGNIFICANCE: SOI and SMI patients have different spectral characteristics in SOP, thus future studies should avoid the inclusion of mixed insomnia samples. PMID- 24239456 TI - Interictal infraslow activity in patients with epilepsy. AB - OBJECTIVE: To evaluate if interictal infraslow activity (ISA), as obtained from a conventional EEG system, can contribute information about the epileptogenic process. METHODS: The entire long-term intracranial monitoring sessions of 12 consecutive patients were evaluated on an XLTEK system for ISA. Three additional patients had long-term scalp recordings. RESULTS: In intracranial as well as scalp recordings, the ISA background was consistently higher in the waking state than during sleep. From this background emerged intermittently focal changes, which could achieve in intracranial recordings millivolt amplitudes, while they remained in the microvolt range in scalp recordings. Although they were mainly contiguous between adjacent channels, this was not necessarily the case and intermittent build-up could be seen distant from the epileptogenic zone or radiographic lesion. CONCLUSIONS: Interictal ISA can be detected in routine intracranial and scalp recordings, without the need for DC amplifiers, and can provide additional information. SIGNIFICANCE: Since ISA is a separate element of the electromagnetic spectrum, apparently non-neuronal in origin, its assessment should be included not only in the pre-surgical evaluation of epilepsy patients but also in patients with other neurologic disorders and normal volunteers. PMID- 24239458 TI - Structural basis for cyclic-nucleotide selectivity and cGMP-selective activation of PKG I. AB - Cyclic guanosine monophosphate (cGMP) and cyclic AMP (cAMP)-dependent protein kinases (PKG and PKA) are closely related homologs, and the cyclic nucleotide specificity of each kinase is crucial for keeping the two signaling pathways segregated, but the molecular mechanism of cyclic nucleotide selectivity is unknown. Here, we report that the PKG Ibeta C-terminal cyclic nucleotide binding domain (CNB-B) is highly selective for cGMP binding, and we have solved crystal structures of CNB-B with and without bound cGMP. These structures, combined with a comprehensive mutagenic analysis, allowed us to identify Leu296 and Arg297 as key residues that mediate cGMP selectivity. In addition, by comparing the cGMP bound and unbound structures, we observed large conformational changes in the C terminal helices in response to cGMP binding, which were stabilized by recruitment of Tyr351 as a "capping residue" for cGMP. The observed rearrangements of the C-terminal helices provide a mechanical insight into release of the catalytic domain and kinase activation. PMID- 24239459 TI - Risk of prostate and bladder cancers in patients with spinal cord injury: a population-based cohort study. AB - OBJECTIVE: To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI). MATERIALS AND METHODS: We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks. RESULTS: Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer. CONCLUSIONS: Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI. PMID- 24239457 TI - Alternate splicing of dysferlin C2A confers Ca2+-dependent and Ca2+-independent binding for membrane repair. AB - Dysferlin plays a critical role in the Ca2+-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca2+ and phospholipid, thus acting as a key sensor in membrane repair. Dysferlin C2A exists as two isoforms, the "canonical" C2A and C2A variant 1 (C2Av1). Interestingly, these isoforms have markedly different responses to Ca2+ and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca2+-dependent, phospholipid binding domain, whereas C2Av1 would likely be Ca2+-independent under physiological conditions. Additionally, both isoforms display remarkably low free energies of stability, indicative of a highly flexible structure. The inverted ligand preference and flexibility for both C2A isoforms suggest the capability for both constitutive and Ca2+-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair. PMID- 24239460 TI - STEAP1 is overexpressed in prostate cancer and prostatic intraepithelial neoplasia lesions, and it is positively associated with Gleason score. AB - BACKGROUND: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a transmembrane protein of epithelial cells, mostly located at cell-cell junctions, and is overexpressed in several types of tumors, particularly prostate cancer. Several studies have pointed STEAP1 as a biomarker, but the clinical significance of its overexpression is not fully understood. Therefore, we aimed to establish the association of STEAP1 immunoreactivity with histologic diagnosis and clinical data of patients. MATERIALS AND METHODS: Human tissue microarrays were constructed from tissue biopsies of prostate adenocarcinoma (n = 63), including nonneoplastic adjacent tissue (n = 41), prostatic intraepithelial neoplasia (PIN) lesions (n = 7), and 41 prostate samples from patients diagnosed with benign prostatic hyperplasia (BPH). The histologic features of tumor specimens were classified and clinical and pathologic data were retrieved. STEAP1 expression was evaluated by immunohistochemical analysis, and a semiquantitative quantification was performed using a grade score system based on the intensity and percentage of stained cells. RESULTS: Overexpression of STEAP1 protein was found in both plasma membrane and cytoplasm of prostate cancer and PIN lesions when compared with nonneoplastic adjacent tissue and BPH samples. Furthermore, its expression associates positively with higher Gleason scores, but not with other clinical data, such as age, prostate-specific antigen levels, pathologic stage, and metastasis. Regarding its role as a biomarker, STEAP1 is highly liable for distinguishing malignant prostate stages from BPH. On the contrary, it lacks specificity in distinguishing PIN lesions from prostate cancer. CONCLUSIONS: STEAP1 is consistently overexpressed in malignant prostate tissue, namely adenocarcinoma and PIN lesions. Its overexpression in PIN lesions and positive association with higher Gleason scores suggest that STEAP1 could be involved in tumor initiation and progression. The high sensitivity and specificity for detection of malignant lesions suggests that STEAP1 may be of clinical usefulness in early disease diagnosis. PMID- 24239461 TI - Boldine induces cell cycle arrest and apoptosis in T24 human bladder cancer cell line via regulation of ERK, AKT, and GSK-3beta. AB - OBJECTIVE: Bladder cancer is one of the most prevalent genitourinary malignancies. Despite active chemotherapy regimens, patients with bladder cancer suffer from a high rate of tumor recurrence. Thus, new approaches and agents to improve quality of life and survival still need to be developed. The objective of the present study was to evaluate the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on bladder cancer proliferation and cell death. METHODS: Sulforhodamine B assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5'-nucleotidase activity and Western blot assay were performed. RESULTS: The results showed that boldine was able to reduce cell viability and cell proliferation in T24 cells. In addition, boldine arrests the cell cycle at G2/M-phase and cause cell death by apoptosis. Boldine-induced inhibition of cell growth and cell cycle arrest appears to be linked to inactivation of extracellular signal-regulated kinase protein (ERK). Additionally, the efficacy of boldine in apoptosis-induced in T24 cells is correlated with modulation of AKT (inactivation) and glycogen synthase kinase 3beta (GSK-3beta) (activation) proteins. CONCLUSIONS: The present findings may, in part, explain the therapeutic effects of boldine for treatment of urinary bladder cancer. PMID- 24239462 TI - Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal cell carcinoma after tumor enucleation. AB - OBJECTIVE: To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically intracapsular renal cell carcinomas (RCCs). METHODS AND MATERIALS: PC status was analyzed in 304 consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were evaluated. Mean (median, range) follow-up was 49 months (46, 25-69). Local recurrence rate, progression-free survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. RESULTS: Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC-), 34.9% had capsular penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side (PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC , PCK, and PCF were 97.5%, 96.7%, and 77.1%, respectively (P<0.0001). The multivariate Cox model showed PCF to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a significant increased risk in developing recurrence. CONCLUSIONS: Tumor enucleation is an oncologically safe nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the risk of recurrence. PMID- 24239464 TI - Biomarkers of renal cell carcinoma. AB - The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease. PMID- 24239463 TI - Implications for human papillomavirus in penile cancer. AB - Human papillomavirus infection (HPV) has been implicated in penile cancer, and although the annual incidence is estimated to be 1,570 in the United States, there are areas of the world in which the incidence is as much as 20-fold higher. Ample data in the literature support testing and vaccination against HPV-related cervical cancer, but for men and penile cancer, these data are lacking. However, some preliminary data would suggest that HPV not only plays an important role in a significant subset of patients with penile cancer but also may be a target for penile cancer prevention as well via initiation of a vaccination program in high risk male populations. PMID- 24239465 TI - The prognostic value of C-reactive protein in renal cell carcinoma: a systematic review and meta-analysis. AB - OBJECTIVES: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in patients with renal cell carcinoma (RCC); however, conflicting results exist. We conducted a systematic review to evaluate the prognostic value, and a meta-analysis was done if the extracted data could be merged. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Search library for published studies that analyzed the effect of CRP in RCC. All included cases were categorized into 4 groups of different stages and tumor types for analysis, and the relationships between CRP and stage, grade, and survival were analyzed. RESULTS: Overall, 24 studies including 4,100 RCC cases were accepted for meta-analysis. Elevated CRP level was associated with higher stage (risk ratio [RR] 2.90, 95% confidence interval [CI] 2.52-3.32, P<0.00001) and higher grade (RR 4.31, 95% CI 3.35-5.56, P<0.00001) in the overall analysis of patients with all pathologic types of RCCs, and it was also associated with poorer overall survival (hazard ratio [HR] 1.51, 95% CI 1.09-1.93, P<0.00001) and cancer-specific survival (CSS) (HR 3.91, 95% CI 2.18-5.64, P<0.00001). In patients with localized RCC, elevated CRP level was associated with poorer CSS (HR 3.49, 95% CI 2.93-4.05, P<0.00001) and progression-free survival (HR 3.29, 95% CI 2.91-3.67, P<0.00001); whereas in patients with metastatic RCC, elevated CRP level was associated with poorer overall survival (HR 2.37, 95% CI 2.14-2.60, P<0.00001) and CSS (HR 3.70, 95% CI 3.19-4.22, P<0.00001). Specifically, in the patients with clear cell RCC, elevated CRP level was also associated with higher stage (RR 2.92, 95% CI 2.25-3.80, P<0.00001), poorer CSS (HR 2.60, 95% CI 2.32 2.88, P<0.00001), and poorer progression-free survival (HR 1.21, 95% CI 0.94 1.47, P<0.00001). CONCLUSION: Elevated CRP level in a patient with RCC is associated with poorer prognosis, and it could serve as a useful biomarker for clinical prediction. PMID- 24239466 TI - Dual inhibition by S6K1 and Elf4E is essential for controlling cellular growth and invasion in bladder cancer. AB - PURPOSE: We investigated how dual inhibition of the molecular mechanism of mammalian target of rapamycin (mTOR) downstream of S6K1 and the eukaryotic initiation factor 4E (eIF4E) can lead to suppression of proliferation and progression of urothelial carcinoma. MATERIALS AND METHODS: We characterized the molecular mechanism of the mTOR pathway in the T24 and 5637 urothelial carcinoma cell lines by interfering with different molecular components using rapamycin and short interfering (siRNA) technology (S6K1 or elF4E) and analyzed the effects on molecular activation status, cell growth, proliferation, and invasion. RESULTS: A high concentration of rapamycin (10 MUM) blocked both S6K1 and elF4E phosphorylation and inhibited cell proliferation in T24 and 5637 cells. The inhibition of both S6K1 and elF4E phosphorylation by rapamycin reduced cell viability and proliferation more than transfection of siRNA against S6K1 or elF4E in 5637 and T24 cells. Cells silenced for S6K1 or elF4E expression exhibited significantly reduced cell migration and invasion compared with those of the control but inhibition of both S6K1 and elF4E phosphorylation by rapamycin reduced cell migration and invasion more than siRNA transfection against S6K1 or elF4E in 5637 and T24 cells. CONCLUSION: These findings suggest that both the mTOR pathway downstream of eukaryotic initiation factor 4E and S6K1 can be successfully inhibited, therefore, the recurrence of bladder cancer can be prevented by high-dose rapamycin only, suggesting that 4E-BP1 might be still under mTORC1. PMID- 24239467 TI - In-hospital death and hospital-acquired complications among patients undergoing partial cystectomy for bladder cancer in the United States. AB - BACKGROUND: Partial cystectomy (PC) is a therapeutic option for select patients with bladder cancer, but its associated perioperative risks and costs are unknown. We estimated annual rates of PC in a nationally representative sample of hospitals, and analyzed whether hospital volume affects postoperative outcomes and costs in patients undergoing PC. METHODS: From the Nationwide Inpatient Sample, we selected a weighted cohort of patients with bladder cancer who underwent PC between 2002 and 2008. Differences in length of stay, charges, and clinical outcomes were calculated based on operative volume, and univariate and multivariate regression models were fitted to predict in-hospital mortality (IHM) and hospital-acquired conditions. RESULTS: A total of 10,780 patients with bladder cancer who underwent PC were identified with an annual rate between 1457 and 1628 cases. IHM rates were 1.8%, constituting 195 patients (between 9 and 46 annually). A total of 417 patients (3.9%) experienced a "never event" complication, which Medicare no longer reimburses. The mean annual hospital volume of patients who died was 1.7 cases/y compared with 2.4 cases/y among those without fatal complications. No cases of IHM were identified among hospitals performing at least 5 partial cystectomies/y. In a multivariate regression model increased hospital volume was independently associated with decreased mortality (odds ratio = 0.70, 95% confidence interval; 0.60-0.80). CONCLUSIONS: Approximately 1 in 25 patients undergoing PC experience a hospital-acquired complication, and nearly 1 in 50 die as a result of the operation. For each additional case a hospital performs annually, the risk of IHM decreases by 30%. PMID- 24239468 TI - Second-line chemotherapy for advanced bladder cancer: a survey of current UK practice. AB - OBJECTIVES: To understand current practice of the treatment of advanced bladder cancer in the United Kingdom, and in particular, the use of second-line chemotherapy.To gain insight into uro-oncologists' use of first-line chemotherapy, imaging following first-line chemotherapy, use of second-line chemotherapy, and the role of the multidisciplinary tumor board (MTB) in making decisions about second-line chemotherapy. MATERIALS AND METHODS: From August 2011 to September 2011 uro-oncologists from UK cancer centers were surveyed regarding treatment of advanced bladder cancer.Delegates at the British Uro-oncology Group conference were invited to fill out an electronic survey. RESULTS: Uro oncologists from 28 of 42 UK cancer centers (67%) participated, who treated, on average 45 patients per year with advanced bladder cancer.Fifteen "always" reimage after first-line chemotherapy, mostly "after 2-4 cycles." Symptomatic patients with progressive distant disease on imaging were most likely to trigger second-line chemotherapy (P = 0.004).Twenty-one respondents would interrupt first line chemotherapy to start second-line chemotherapy for progressive disease and 10 would never do this. Of the patients given first-line chemotherapy, 19% go on to receive second-line chemotherapy.Seven different regimes were specified for second-line chemotherapy with no clear preference. National Institute for Health and Clinical Excellence approval, trial data, inclusion in hospital formulary, clinical trials, or commissioning guidelines, and easy access to imaging help to access second-line chemotherapy (P <= 0.001). Constraints to second-line chemotherapy were lack of evidence and patient comorbidities.MTB effectiveness did not improve access to second-line chemotherapy. Of the 33 respondents, 19 do not rediscuss patients at the MTB before starting second-line chemotherapy. CONCLUSION: The investigation and treatment of patients with advanced bladder cancer following first-line chemotherapy is variable.Optimizing the modality and frequency of imaging and increasing the usefulness of the MTB process may improve care. PMID- 24239469 TI - Prostate-specific antigen growth rate constant after first-line cytotoxic chemotherapy in metastatic castration-resistant prostate cancer: a monoinstitutional experience. AB - OBJECTIVE: Validation in clinical practice, after first-line chemotherapy (CT) of metastatic castration-resistant prostate cancer (PC), of prostate-specific antigen growth rate constant logarithm (PSA-G), calculated by a formula developed by Stein et al. in comparison with PSA decrease (PSA-D), calculated as recommended by PCWG2. PATIENTS AND METHODS: This study is a retrospective monoinstitutional assessment of PSA-G and PSA-D after 12 weeks from the beginning of first-line cytotoxic CT in 49 patients with metastatic castration-resistant PC treated from 2006 to 2011, and whose pre-CT PSA and post-CT PSA determinations have been measured at specific time points. The 12-week PSA was measured at 80 to 91 days from the beginning of CT. RESULTS: PSA-G exhibited a significant correlation with overall survival by Mann-Whitney U test and by linear regression, whereas PSA-D did only at the first test. After multivariate analysis, PSA-G was the only posttreatment measure to predict overall survival. CONCLUSION: PSA-G appears a reliable surrogate end point after first-line cytotoxic CT outside of clinical trials. A cutoff value of PSA-G post-CT higher than-2.4 could be considered suggestive for moving to another treatment. PMID- 24239470 TI - The prostate cancer genome: perspectives and potential. AB - OBJECTIVES: Prostate cancer has a variable clinical course, and molecular characterization has revealed striking mutational heterogeneity that may underlie the unpredictable clinical behavior of the disease. Advances in technology have resulted in a rapid expansion of our understanding of the genomic events responsible for the development and progression of prostate cancer. In this review, we discuss the genomic alterations underlying prostate cancer, and potential to utilize this knowledge for diagnostic and prognostic benefit. METHODS AND MATERIALS: We reviewed the relevant literature, with a focus on recent studies on somatic alterations in prostate cancer. RESULTS: Pathways known to affect tumorigenesis across a wide spectrum of tissues are dysregulated, such as the PI3K pathway, cell cycle control, and chromatin regulation. Lesions more specific to prostate cancer include alterations in androgen signaling, gene fusions of ETS transcription factors, and mutations in SPOP. Accumulating data suggests that prostate cancer can be subdivided based on a molecular profile of these genetic alterations. CONCLUSIONS: These findings raise the possibility that prostate cancer could transition from a poorly understood, heterogeneous disease with a variable clinical course to a collection of homogenous subtypes, identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies. PMID- 24239471 TI - Urinary tract infections in patients with orthotopic neobladder. AB - OBJECTIVE: Orthotopic neobladder urinary diversion is associated with a high rate of infectious complications, especially in the early postoperative period. The aim of the study was to assess the incidence, associated pathogens, and predictors of symptomatic urinary tract infection (UTI) in patients with an orthotopic neobladder. METHODS AND MATERIALS: The medical records of 79 patients treated with radical cystectomy and orthotopic neobladder urinary diversion at a tertiary medical center in 2004 to 2012 were reviewed for data pertaining to bacteriuria and symptomatic UTI after hospital discharge. Cumulative incidences of clinical events were assessed with the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify clinical predictors of infection. RESULTS: A total of 69 men and 10 women were included in the study cohort. The estimated cumulative rates of symptomatic UTI were 34% at 3 months, 40% at 6 months, and 43% at 12 months. New events of symptomatic UTI occurred in 36% of the patients during the first 3 postoperative months, but only in 10% at 3 to 6 months and 8% at 6 to 12 months. Common pathogens were Pseudomonas aeruginosa (24%) and Escherichia coli (24%); 78% of bacterial pathogens were susceptible to amikacin. On multivariate analysis, there was no effect of age, gender, intermittent catheterization, bowel segment used for reconstruction, or perioperative chemotherapy on rates of UTI. CONCLUSIONS: Symptomatic UTI is a common complication after neobladder reconstruction, usually occurring within the first 3 months of surgery. P. aeruginosa infection is common. Inpatient empirical treatment with amikacin is recommended in this setting. PMID- 24239472 TI - Precision medicine for metastatic renal cell carcinoma. AB - OBJECTIVES: This review provides a broad overview of emerging data that provide hope that rational precision medicine for metastatic renal cell carcinoma (RCC) may be possible. METHODS: PubMed and major conferences were searched for studies reporting potential predictive biomarkers for the therapy of metastatic RCC. RESULTS: The availability of multiple new agents for the therapy of advanced RCC poses new challenges in terms of optimal selection of patients for the appropriate drug. Prognostic stratification based on routine histopathologic, clinical and laboratory factors have been utilized to broadly select individuals based, i.e. high-dose interleukin (IL)-2 or vascular endothelial growth factor (VEGF) inhibitors for good and intermediate risk patients and temsirolimus for poor risk patients. While multiple candidate predictive molecular biomarkers suggest that rational selection of patients for high-dose interleukin (IL)-2, and VEGF and mammalian target of rapamycin (mTOR) inhibitors may be possible, none have been validated for use in the clinic. Tumor heterogeneity and standardization of tissue collection and analysis are massive challenges that need to be addressed. Predictive molecules derived from tumor tissue, plasma and host tissue may all be predictive for therapeutic benefit. Moreover, gene expression may be modulated by multiple factors including epigenetics, transcription factors and post-transcriptional and post-translational modifications. Indeed, study of the interaction of molecular factors from all of these sources with environmental and clinical factors may be necessary to develop a unified profile composed of a panel of factors predictive of benefit from specific agents (i.e. sustained response, limited toxicity and overall a positive benefit/risk ratio). CONCLUSIONS: Conducting clinical trials with 1) prospective incorporation of promising candidate predictive molecular biomarkers, 2) novel biomarkers endpoints, and 3) mandatory biopsies of metastatic sites at different time points on therapy, are potential important steps in developing the concept of "the right medication for the right patient". PMID- 24239473 TI - Target detection: magnetic resonance imaging-ultrasound fusion-guided prostate biopsy. AB - Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance. PMID- 24239474 TI - Expression of molecular markers associated with the mammalian target of rapamycin pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following radical nephrectomy. AB - OBJECTIVES: To evaluate the expression of multiple molecular markers involved in mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic significance of these markers following radical nephrectomy. MATERIAL AND METHODS: The expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic RCC by immunohistochemical staining. RESULTS: During the follow-up period of this series (median, 63.5 mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p 4E-BP1, in addition to the C-reactive protein level, pathological stage, and microvascular invasion, were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level, and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor (46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). CONCLUSIONS: The combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC. PMID- 24239475 TI - Primary spermatic cord tumors: disease characteristics, prognostic factors, and treatment outcomes. AB - INTRODUCTION: Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a large population-based cancer registry to characterize the demographic, pathological, treatment characteristics, and outcomes of SCTs. MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results database (1973-2007) was queried. RESULTS: From the database, 362 patients were identified with SCT. The annual incidence of SCT was 0.3 cases per million and did not change over time. The most common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for other SCTs, it was (64.7 y) (P<0.001). On multivariate analysis, a worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma cell histology. CONCLUSION: We describe the largest cohort of SCT studied to date. Liposarcoma was most common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node involvement were independently predictive of prognosis. PMID- 24239476 TI - Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. AB - OBJECTIVE: The oncological basis behind the observation that females experience worse outcomes following radical cystectomy for urothelial carcinoma of the bladder (UCB) is unclear. This study was aimed at examining the sole effect of gender on postcystectomy UCB outcomes and identifying potential factors that may explain the poor prognosis in females using a balanced case-control approach. MATERIALS AND METHODS: A review of 2,567 patients with UCB who underwent radical cystectomy identified 414 females ("cases") who were matched 1:1 for demographic, tumor, and treatment characteristics with 414 male counterparts ("controls"). Cases were also compared with an independent male UCB cohort (n = 1,166). Differences between females vs. matched control and independent male patients with UCB were analyzed. Recurrence-free survival, cancer-specific survival, and overall survival were compared by univariable and multivariable Cox regression models. RESULTS: Median follow-up for cases, controls, and independent control cohort was 12.2, 8.6, and 13.5 years, respectively. Females were matched to male controls for tumor and nodal stages (P = 1.00), lymphovascular invasion and surgical margin status, age, prior intravesical treatment, and neoadjuvant and adjuvant chemotherapy administration (P = 0.61-1.00). Cases were also balanced with controls for grade, p53 status, nodal yield, American Society of Anesthesiologists score, presence of hydronephrosis, and times to diagnosis and cystectomy (P >= 0.14). When thus matched, outcomes between females and males were not different (P >= 0.34). However, when compared with an independent unmatched male control cohort, females had significantly poorer outcomes (P <= 0.006). In this comparison, females presented with higher tumor (P<0.001) and nodal (P = 0.049) stages and a lesser proportion received precystectomy intravesical therapy (P = 0.032). CONCLUSIONS: Females have similar UCB outcomes to males when matched for demographic, clinicopathologic, and management characteristics. However, they present with more advanced tumors, thus explaining the observation of poor outcomes. PMID- 24239477 TI - Cognitive processes associated with compulsive buying behaviours and related EEG coherence. AB - The behavioural and cognitive phenomena associated with Compulsive Buying (CB) have been investigated previously but the underlying neurophysiological cognitive process has received less attention. This study specifically investigated the electrophysiology of CB associated with executive processing and cue-reactivity in order to reveal differences in neural connectivity (EEG Coherence) and distinguish it from characteristics of addiction or mood disorder. Participants (N=24, M=25.38 yrs, S.D.=7.02 yrs) completed the Sensitivity to Punishment Sensitivity to Reward Questionnaire and a visual memory task associated with shopping items. Sensitivities to reward and punishment were examined with EEG coherence measures for preferred and non-preferred items and compared to CB psychometrics. Widespread EEG coherence differences were found in numerous regions, with an apparent left shifted lateralisation for preferred and right shifted lateralisation for non-preferred items. Different neurophysiological networks presented with CB phenomena, reflecting cue reactivity and episodic memory, from increased arousal and attachment to items. PMID- 24239478 TI - 17beta-carboxamide steroids--in vitro prediction of human skin permeability and retention using PAMPA technique. AB - In this paper, twenty-two 17beta-carboxamide steroids were synthesized from five corticosteroids (hydrocortisone, prednisolone, methylprednisolone, dexamethasone and betamethasone) in two steps. The first step was periodic acid oxydation of these corticosteroids to corresponding cortienic acids and the second step was amidation of thus obtained cortienic acids with esterified l-amino acids. These compounds are potential soft corticosteroids with local anti-inflammatory activity in the skin. Parallel artificial membrane permeability assay (PAMPA) was applied in order to predict permeability and retention of these compounds in human skin. Comparison of permeability and retention parameters between 17beta carboxamide steroids and corresponding corticosteroids was performed. Compounds with significantly higher retention were identified and the derivative that does not have significantly higher permeability was underlined. Molecular structures of all compounds were optimized by use of Gaussian semiempirical/PM3 method. Geometrical, thermodynamic, physicochemical and electronical molecular parameters of the optimized structures were calculated and quantitative structure-property relationship (QSPR) analysis was performed in order to explain permeability and retention of these compounds. ANN-, PLS- and MLR-QSPR models were created. Quality of these models was evaluated by commonly used statistical parameters and the most reliable models were selected. Analyzing descriptors in the selected models, main molecular properties that influence permeability and retention in the PAMPA artificial membrane were identified. Based on these data, further structural modifications could be applied in order to increase retention without significant increase of permeability, which can positively affect potential local anti-inflammatory activity of these compounds. Selected QSPR models could be used as in silico tool for predicting human skin permeability and retention of novel 17beta-carboxamide steroids without performing PAMPA experiments. PMID- 24239479 TI - [Complete fertilization failure following conventional IVF or ICSI: is it predictable? How to manage?]. AB - The occurrence of complete fertilization failure following conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is a rare event. Each of six physiological stages of the fertilisation can be failing. The cause of a fertilisation failure is either the spermatozoa, or the oocyte. The aim of this study was to determine if this event is predictable, and to define the later strategy. On all sperm tests available, it seems that only, tests of zona pellucida binding and acrosomique reaction are relatively predictive of a complete fertilization failure after IVF. No test allows at the moment to predict an oocyte contribution to unsuccessful fertilization. The strategy retained after a complete fertilization failure following the first attempt of IVF is to propose an ICSI; either to do an IVF if this event arises in the rank n+1, or when the number of inseminated oocytes was low. Concerning the ICSI, the low number of micro-injected oocyte is often in question; so the strategy retained following a first fertilization failure after ICSI is to perform a new ICSI attempt after optimization of the ovarian stimulation. When the cause is spermatic, it is indicated trying a modified ICSI with the use of pentoxifiline, or an intracytoplasmic morphologically selected sperm injection (IMSI), sometimes with assisted oocyte activation. In last solution, we can propose the ovum donation. PMID- 24239480 TI - Risk assessment of neonatal excipient exposure: lessons from food safety and other areas. AB - Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates without obvious adverse effects. Some excipients may be toxic in high amounts in which case they need careful risk assessment. Alternatively, it is conceivable that ill-founded fears about excipients mean that potentially useful medicines are not made available to newborn babies. Choices about excipient exposure can occur at several stages throughout the lifecycle of a medicine, from product development through to clinical use. Making these choices requires a scalable approach to analysing the overall risk. In this contribution we examine these issues. PMID- 24239481 TI - Novel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. AB - A series of novel piperidinylamino-diarylpyrimidine (pDAPY) derivatives with dual structural conformations was designed through a molecular hybridization strategy and expected to bind into the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-1 RT in a flexible manner. A cell-based antiviral screening assay showed that some compounds were active against both wild-type and drug-resistant mutant virus strains (K103N+Y181C RT) of HIV-1 (compound 10b3 with EC50 = 0.047 and 4.6 MUM, selectivity index = 2145 and 22, respectively). Molecular simulation studies indicated that compound 10b3 could maintain the key hydrophobic interaction and hydrogen bonds with the NNIBP of two RT/ligand complexes. In particular, it could simultaneously occupy the protein/solvent interface and the entrance channel. Exploring these hybrid molecules with dual binding conformations might provide optional chemical scaffolds as novel HIV-1 reverse transcriptase inhibitors (HIV 1 NNRTIs). PMID- 24239482 TI - Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia. AB - Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. PMID- 24239483 TI - What do diagnostic test data tell us about differences in the profiles of children diagnosed with reading disability or language impairments? AB - A detailed evaluation of a child's strengths and weaknesses allows for a valid and reliable diagnosis of reading disability for the selection of optimal intervention practices. Using archival data from a clinic that specialized in the diagnosis of reading disabilities, we compared the performance of 60 children diagnosed with specific reading disability (SRD) and 31 children with language impairments and reading disability (LIRD) on measures of cognitive reasoning, verbal ability, phonological manipulation, rapid serial naming, and phonological memory. While the SRD and LIRD groups did not differ in their phonological processing, children with LIRD performed significantly below their peers with SRD on thinking ability and verbal ability measures. Rapid naming skills served as current predictors of text reading fluency and verbal ability skills served as concurrent predictors of reading comprehension in both groups. These findings highlight the need for reading diagnosticians to conduct comprehensive evaluations using a range of cognitive and language processes to ensure the most accurate and specific diagnoses of children with reading disabilities. LEARNING OUTCOMES: Readers will be able to (a) describe general characteristics of reading disabilities, (b) differentiate features of two learning disabilities, specific reading disability and language impairments and reading disability, and (c) identify key clinical issues and approaches for identification, diagnosis, and intervention of these two diagnostic profiles. PMID- 24239484 TI - Performance on verbal and low-verbal false belief tasks: evidence from children with Williams syndrome. AB - Previous studies that have investigated the relationship between performance on theory of mind (ToM) tasks and verbal abilities in individuals with Williams syndrome (WS) have reported contradictory findings with some showing that language abilities aid performance on ToM tasks while others have found that participants with WS fail these tasks because of their verbal demands. The current study investigated this relationship again comparing performance on a classical change-location task to two newly developed low-verbal tasks, one change-location task and one unexpected content task. Thirty children with WS (aged 5-17;01 years) and 30 typically developing (TD) children (aged between 2;10 years and 9;09 years), who were matched for vocabulary comprehension scores were included in the study. Although performance in the WS group was significantly poorer compared to the TD group on all three tasks, performance was not predicted by their receptive vocabulary or grammatical ability scores. In addition, ToM abilities in both groups depended on the cognitive demands of the task at hand. This finding shows that performance on ToM tasks in WS is not necessarily hindered by their delayed language abilities but rather by the task administered. This could potentially affect the diagnosis of developmental disorders, such as Autism Spectrum Disorders, and comparison of ToM abilities across developmental disorders. LEARNING OUTCOMES: Readers of this article should be able to (1) describe the current state of theory of mind research in Williams syndrome, (2) identify which cognitive abilities might explain performance on theory of mind tasks in both typically developing children and in children with Williams syndrome, and (3) interpret the importance of task demands when assessing children's theory of mind abilities. PMID- 24239485 TI - Free fatty acids and protein kinase C activation induce GPR120 (free fatty acid receptor 4) phosphorylation. AB - GPR120, free fatty acid receptor 4, is a recently deorphanized G protein-coupled receptor that seems to play cardinal roles in the regulation of metabolism and in the pathophysiology of inflammatory and metabolic disorders. In the present work a GPR120-Venus fusion protein was expressed in HEK293 Flp-In T-REx cells and its function (increase in intracellular calcium) and phosphorylation were studied. It was observed that the fusion protein migrated in sodium dodecyl sulfate polyacrylamide gels as a band with a mass of ~70-75kDa, although other bands of higher apparent weight (>130kDa) were also detected. Cell stimulation with docosahexaenoic acid or alpha-linolenic acid induced concentration-dependent increases in intracellular calcium and GPR120 phosphorylation. Activation of protein kinase C with phorbol esters also induced a marked receptor phosphorylation but did not alter the ability of 1uM docosahexaenoic acid to increase the intracellular calcium concentration. Phorbol ester-induced GPR120 phosphorylation, but not that induced with docosahexaenoic acid, was blocked by protein kinase C inhibitors (bis-indolyl-maleimide I and Go 6976) suggesting that conventional kinase isoforms mediate this action. The absence of effect of protein kinase C inhibitors on agonist-induced GPR120 phosphorylation indicates that this kinase does not play a major role in agonist-induced receptor phosphorylation. Docosahexaenoic acid action was associated with marked GPR120 internalization whereas that induced with phorbol esters was smaller at early times. PMID- 24239486 TI - The reproducibility comparison of two intervertebral translation measurements in cervical flexion-extension. AB - BACKGROUND CONTEXT: The abnormal translations between vertebrae in the sagittal plane are important clues to spinal dysfunction or instability. Several studies have reported significant variability in their translation measurements with no analysis of data reproducibility. PURPOSE: We sought to determine the intra- and interobserver reproducibility of the computer-assisted geometric midplanes and rotation matrix methods in the measurements of intervertebral translations at different motion ranges of cervical flexion-extension in asymptomatic subjects and disc-herniated patients. STUDY DESIGN: A blind, repeated-measure design was applied to determine the reproducibility for intervertebral translation measurements. METHODS: A total of 608 videofluoroscopic image sequences from the different motion ranges of cervical flexion and extension in 38 asymptomatic subjects and 38 disc-herniated patients were digitized for further analysis. RESULTS: The intra- and interobserver reproducibility on measuring the sequential translations were in the acceptable range for geometric midplanes method (average intraclass correlation coefficients [ICCs], 0.860 and 0.806; mean absolute difference [MAD] 0.19 and 0.33 mm) and rotation matrix method (average ICCs, 0.807 and 0.735; MAD, 0.35 and 0.42 mm). There was significantly better reproducibility on the measurements of intervertebral translation for the geometric midplanes method than those of rotation matrix method (p=.001-.040). The absolute mean differences of the translation measurements between two image protocols averaged 11.2% and 10.8% for the asymptomatic subjects and disc herniated patients, respectively. CONCLUSIONS: Based on these results, both methods demonstrated acceptable reproducibility on the intervertebral translation measurements. The geometric midplanes method involving an averaging effect on the placements of vertebral landmarks and closer to center of rotation might reduce the errors in translation estimations. The rotation matrix protocol simultaneously illustrated horizontal and vertical translation motion despite greater digitizing and/or measurement errors. PMID- 24239487 TI - The relationship between an intramedullary high signal intensity and the clinical outcome in atlanto-axial subluxation owing to rheumatoid arthritis. AB - BACKGROUND CONTEXT: In patients affected by cervical spondylotic myelopathy (CSM), numerous authors have reported the existence of a relationship among the intramedullary high signal intensity in T2-weighted MRIs, preoperative neurologic severity, and neurologic recovery after surgery; however, to our knowledge, there have been no previous reports that have described its relationship in patients with atlanto-axial subluxation (AAS) owing to rheumatoid arthritis (RA). PURPOSE: The purpose of this study was to clarify the characteristics of patients with AAS owing to RA showing intramedullary high signal intensity in T2-weighted MRIs, and to assess the relationship with the neurologic severity and neurologic recovery after surgery. STUDY DESIGN: This was a retrospective cohort study. PATIENTS SAMPLE: Fifty consecutive patients (37 females and 13 males) with AAS treated by surgery were reviewed. OUTCOME MEASURES: The outcome was determined 1 year after surgery. METHODS: According to preoperative T2-weighted MRIs, the patients were classified into two groups as follows: An NC group not showing any signal intensity change on sagittal images, and an SI group showing signal intensity changes with narrowing of the spinal cord. In all patients, we investigated the atlanto-dental distance (ADD) and the space available for the spinal cord (SAC) at the neutral position and the maximal flexion position in lateral cervical radiographs before surgery. We also observed MRIs 1 year after surgery in the SI group. We evaluated the severity of neurologic symptoms before and 1 year after surgery in all patients. RESULTS: Preoperative T2-weighted MRIs demonstrated NC in 38 cases and SI in 12 cases. The preoperative average ADD at the neutral position in the NC and SI groups was 6.4 and 10.2 mm, respectively (p<.01). The preoperative ADD at the maximal flexion position in the two groups were 10.8 and 13.8 mm, respectively (p<.01). The preoperative average SAC at the neutral position in the NC and SI groups were 17.6 and 13.8 mm, respectively (p<.01). The SAC at the maximal flexion position in the two groups were 14.3 and 10.8 mm, respectively (p<.01). The SI group included significantly more Ranawat grade III cases showing severe neurologic deficits compared to the NC group (p<.01). However, there were no differences between the two groups regarding the number of patients with Ranawat grade III status after surgery (p>.65). On MRIs 1 year after surgery, the regression or disappearance of the signal intensity change in T2-weighted images was demonstrated in four and seven cases, respectively. CONCLUSIONS: Preoperative ISHI in T2-weighted MRIs in RA-induced AAS patients was demonstrated in patients showing an enlargement of the ADD and a narrowing of the SAC. This affected the preoperative neurologic severity, but not the postoperative severity, which was in contrast to CSM patients. Furthermore, the regression or disappearance of ISHI was demonstrated in all of the cases after surgery. It is therefore speculated that RA AAS patients may have both dynamic instability and stenosis. PMID- 24239488 TI - Morphologic changes in the lumbar spine after lumbar medial branch radiofrequency neurotomy: a quantitative radiological study. AB - BACKGROUND CONTEXT: Medial branch radiofrequency neurotomy (RFN) is a common treatment for zygapophyseal joint pain. The lumbar medial branch innervates these joints and adjacent structures. The impact of the intended neurotomy on these structures remains unclear. No studies have yet verified quantitatively the effect of medial branch RFN on intervertebral discs, facet joints, and multifidus cross-sectional area. PURPOSE: The aim of this study was to determine, using objective radiographic measures, whether there is a quantitative difference in the lumbar multifidus muscle cross-sectional area, facet joint degeneration, or intervertebral disc degeneration after segmental medial branch RFN. STUDY DESIGN/SETTING: This is a retrospective single-cohort study performed at a university spine center. PATIENT SAMPLE: The patient sample consisted of 27 patients treated with lumbar medial branch RFN, with pre- and posttreatment magnetic resonance images available for analysis. OUTCOME MEASURE: The primary study outcome measure was interval change in fat-subtracted multifidus cross sectional area, and intervertebral disc and zygapophyseal joint degeneration grade. METHODS: In this retrospective study, segmental levels unaffected by RFN treatment were used as controls to compare against levels affected by treatment. RESULTS: Levels affected by RFN demonstrated a significantly greater amount of disc degeneration compared with unaffected levels (14.9% vs. 4.6%; p=.0489). There was no statistical difference in the multifidus cross-sectional area or rates of deterioration in the zygapophyseal joints observed. CONCLUSIONS: The full impact of RFN on multifidus function, morphology, and segmental anatomy is unknown. This retrospective study indicates that measurable changes in segmental morphology may occur after lumbar medial branch RFN. These findings require validation in a prospective, controlled study. PMID- 24239489 TI - Persistent phosphorylation of NKCC1 and WNK1 in the epicenter of the spinal cord following contusion injury. AB - BACKGROUND CONTEXT: NKCC1 regulates neuronal homeostasis of chloride ions and mediates GABAergic activities in nociceptive processing. WNK1 is an upstream regulator of NKCC1 and acts via SPAK (STE20/SPS1-related proline/alanine-rich kinase) and oxidative stress-responsive kinase 1. NKCC1 activity has been shown to be important in edema formation and nociception following spinal cord injury (SCI). PURPOSE: To determine the role of NKCC1 and WNK1 in spinal cord tissues in the acute and chronic phases following contusional SCI. STUDY DESIGN: An experimental study investigating the phosphorylation profile of an important Cl regulatory protein Na+-K+-Cl- cotransporter 1 (NKCC1) and its regulatory-kinase WNK1 (kinase with-no-lysine). METHODS: Sprague-Dawley rats underwent a contusive SCI at T9. The epicenter spinal cord tissues were harvested at Days 1, 3, and 7 for acute phase of injury or Days 35 and 42 in the chronic phase of injury. Western blot was used to compare phosphorylated levels of both NKCC1 and WNK1 in injured tissues compared with those of sham. RESULTS: A sustained increase in phosphorylation of NKCC1 and WNK1 was detected in the lesion epicenter in spinal cord during both acute and chronic phases following SCI. CONCLUSIONS: These results suggest that persistent activation of NKCC1 and WNK1 may play an important role in SCI. PMID- 24239490 TI - An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. AB - BACKGROUND CONTEXT: The objective of the North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of lumbar disc herniation with radiculopathy. The guideline is intended to reflect contemporary treatment concepts for symptomatic lumbar disc herniation with radiculopathy as reflected in the highest quality clinical literature available on this subject as of July 2011. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder. PURPOSE: To provide an evidence-based educational tool to assist spine specialists in the diagnosis and treatment of lumbar disc herniation with radiculopathy. STUDY DESIGN: Systematic review and evidence-based clinical guideline. METHODS: This guideline is a product of the Lumbar Disc Herniation with Radiculopathy Work Group of NASS' Evidence-Based Guideline Development Committee. The work group consisted of multidisciplinary spine care specialists trained in the principles of evidence-based analysis. A literature search addressing each question and using a specific search protocol was performed on English-language references found in Medline, Embase (Drugs and Pharmacology), and four additional evidence-based databases to identify articles. The relevant literature was then independently rated using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final recommendations to answer each clinical question were developed via work group discussion, and grades were assigned to the recommendations using standardized grades of recommendation. In the absence of Level I to IV evidence, work group consensus statements have been developed using a modified nominal group technique, and these statements are clearly identified as such in the guideline. RESULTS: Twenty-nine clinical questions were formulated and addressed, and the answers are summarized in this article. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. CONCLUSIONS: The clinical guideline has been created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with symptomatic lumbar disc herniation with radiculopathy. The entire guideline document, including the evidentiary tables, suggestions for future research, and all the references, is available electronically on the NASS Web site at http://www.spine.org/Pages/PracticePolicy/ClinicalCare/ClinicalGuidlines/Default. spx and will remain updated on a timely schedule. PMID- 24239491 TI - A comparison of risk factors for women seeking labiaplasty compared to those not seeking labiaplasty. AB - Little is known about the factors associated with the desire for labiaplasty. We compared 55 women seeking labiaplasty with 70 women in a comparison group who were not seeking labiaplasty. Measures administered included the Perception of Appearance and Competency Related Teasing Scale, Childhood Trauma Questionnaire, Disgust Scale Revised, and the Genital Appearance Satisfaction scale with open ended questions about their genitalia. Approximately a third of the labiaplasty group recalled specific negative comments in the past towards their labia, a proportion significantly greater than the three per cent in the comparison group. Participants reporting genital teasing also showed higher Genital Appearance Satisfaction scores than those who were not teased. However, women seeking labiaplasty were, compared to the comparison group, no more likely to have a history of neglect or abuse during childhood. There was no difference between the groups on disgust sensitivity or the perception of being teased in the past about their competence or appearance in general. PMID- 24239492 TI - Designing reaction-based fluorescent probes for selective hydrogen sulfide detection. AB - Hydrogen sulfide (H2S) is a biologically generated, gaseous signaling molecule that mediates a wide range of physiological functions and is misregulated in numerous pathologies ranging from neurodegenerative disease to hypertension to diabetes. Despite swelling interest, a deeper understanding of the biological roles played by H2S has been hindered by a lack of tools for the real-time visualization of its production in living organisms. Recently, reaction-based fluorescent probes have emerged as an ideal approach for selective H2S imaging and are attracting increasing attention with many new innovative designs being introduced. This review will highlight some of the most fruitful reaction-based strategies, including reduction-based, nucleophilic-based, and metal sulfide precipitation-based fluorescent sensors. Strategies to address the key design challenges of sensitivity, selectivity, in vivo compatibility, and quantification will be discussed using examples of recently developed molecular scaffolds for selective H2S detection. PMID- 24239493 TI - Limb compression induces multi-system genetic damage in rats. AB - Muscle crush injury is a common trauma in the modern society after as a result of mass disasters after penetration into muscle by high-velocity projectiles, blunt external trauma, or by gravity during prolonged immobilization in comatose patients after head trauma, alcoholic or drug overdose. However, the underlying mechanisms linking these alterations are still not fully understood, especially in acute phase. The aim of this study was to analyze genomic instability in multiple organs of rats after acute muscle injury by means of single cell gel (comet) assay. Rats were randomly distributed into three groups (n=6 each group): control group and experimental groups: sacrificed 6h as 12h after muscle compression. These results indicate genetic damage in peripheral blood cells as depicted by tail moment results. DNA breakage was also detected in liver, lung and kidney cells after acute muscle injury for two times evaluated. Heart cells showed genetic damage after 12h following muscle compression. Taken together, our results suggest that acute muscle injury induces genomic damage in multiple organs of Wistar rats. This novel finding offers new insights into the underlying mechanisms of the relationship between acute crush muscle injury and clinical manifestations that can occur during limb compression. PMID- 24239494 TI - ED placement of perineural catheters for femoral fracture pain management. AB - Regional nerve blocks provide superior analgesia over opioid-based pain management regimens for traumatic injuries such as femur fractures. An ultrasound guided regional nerve block is placed either as a single-shot injection or via a perineural catheter that is left in place. Although perineural catheters are commonplace in the perioperative setting, their use by emergency physicians (EPs) for emergency pain management in adults has not been previously described. Perineural catheters allow prolonged and titratable delivery of local anesthetic directly targeted to the injured extremity, resulting in opioid sparing while maintaining high-quality pain relief with improved alertness. Despite these advantages, most EPs do not currently place perineural catheters, likely due to the widespread perception that the procedure is both excessively time consuming and too technically difficult to be practical in a busy emergency department (ED). A catheter-over-needle kit, resembling a peripheral intravenous line, is now available and may be familiar to EPs than traditional catheter-needle assemblies. Recent studies also suggest excellent analgesic outcomes with intermittent perineural bolusing of local anesthetic, thereby dispensing with the need for complex and expensive infusion pumps. Herein, we describe our successful placement of perineural femoral catheters at a busy inner-city public hospital ED. Our experience suggests that this is a promising new technique for emergency pain management of acute extremity injuries. PMID- 24239495 TI - Analysis of parameters influencing the release of antibiotics mixed with bone grafting material using a reliable mixing procedure. AB - Local infections arising from fracture fixation, defect reconstruction or joint replacement can cause extreme pain and impaired healing, lead to revision operations, prolong hospital stay and increase costs. Treatment options including prophylaxis are afforded by the use of grafts and biomaterials loaded with antibiotics. These can produce local therapeutic concentrations with a reduced systemic concentration and reduced systemic side-effects. Patient-specific loading of osteogenic graft materials with antibiotic could be an important option for orthopaedic surgeons. A local therapeutic concentration must be available for the desired duration and cytotoxic effects must be kept within an acceptable range. The present study investigates a simple and reliable mixing procedure that could be used for the perioperative combination of antibiotic powders and solutions with bone grafting materials. The potential influence of concentration and sampling regime on the release kinetics of gentamicin, tobramycin and vancomycin was studied over a period of 56days and potency and cytotoxicity were evaluated. In all treatment groups, gentamicin and tobramycin were completely released within 3days whilst vancomycin was released over a period of 14days. The results clearly show that the main parameter influencing release is the molecular weight of the drug. Growth of Staphylococcus aureus was inhibited in all 3 treatment groups for at least 3days. Cell viability and alkaline phosphatase activity of primary osteoblast-like cells were not significantly affected by the antibiotic concentrations obtained from the elution experiments. Bone grafting is an established component of surgery for bone defect filling and for biological stimulation of healing. Patient-specific enhancement of such procedures by incorporation of antibiotics for infection prevention or by addition of cytokines for promotion of impaired healing or for treatment of critical size defects will be a relevant issue in the future. PMID- 24239496 TI - Sleep and eating in childhood: a potential behavioral mechanism underlying the relationship between poor sleep and obesity. AB - OBJECTIVE: The goal of our study was to examine the associations between sleep and eating behaviors. Specifically, we examined associations between sleep duration and continuity with behaviors that promote eating regardless of true physiologic hunger state including emotional (food intake in response to emotional distress) external (eating in response to the sight or smell of food), and restrained eating (a paradoxical behavior; food intake is initially reduced to lose or maintain body weight, but followed by increased consumption and binge eating). PARTICIPANTS: Fifty-six children (29 boys; 27 girls) ages 5 to 12 years participated in the study. Mean age was 7.7+/-1.9 years, and average body mass index (BMI) was within the healthy range (17.8+/-4.3 kg/m(2)). METHODS: Sleep duration, continuity and schedule were assessed using actigraphy and self reports. The Child Dutch Eating Behavior Questionnaire-modified version (DEBQ-M) was used to examine levels of emotional, external and restrained eating in the children. RESULTS: Associations between the sleep and eating behaviors were examined using partial correlations and multiple regression analyses. External eating score was negatively associated with sleep duration; emotional eating score was associated with lower levels of sleep continuity; and restrained eating score were associated with a later sleep start and later bedtime. CONCLUSIONS: Short sleep duration and poor sleep continuity were associated with higher levels of eating behaviors shown to be associated with increased food intake. Therefore, sleep loss may be associated with diminished self-regulation of appetite in children, increasing the risk for overeating and obesity. PMID- 24239497 TI - Long-term changes in blood pressure control in elementary school-aged children with sleep-disordered breathing. AB - OBJECTIVE: In adults sleep-disordered breathing (SDB) has been associated with impaired baroreflex control of blood pressure (BP), which has been linked to increased cardiovascular morbidity. In children, the long-term effects of SDB on baroreflex sensitivity (BRS) and BP variability (BPV) are unknown. METHODS: Children previously diagnosed with SDB (n=40) and 20 nonsnoring controls aged 11 16 y underwent overnight polysomnography with continuous BP measurement, four years after the original diagnosis. At follow-up, SDB was categorized as resolved (absence of snoring and obstructive apnea hypopnea index (OAHI)<=1) or unresolved (continued to snore or had an OAHI>1). BRS and BPV were calculated using cross spectral analysis and power spectral analysis, respectively. RESULTS: Only children with resolved obstructive sleep apnea (OSA) at follow-up demonstrated an increase in BRS from 9.7+/-3 (ms mmHg(-1)) at baseline to 11.8+/-4 (ms mmHg(-1)) at follow-up (P=.03). However, children with all severities of both resolved and unresolved SDB showed a significant decrease in BPV from baseline to follow-up (a decrease in total power BPV (P<.05) and a shift in BPV spectra away from respiratory-related frequencies (increased low-frequency/high-frequency [LF/HF] ratio, P<.01). The change in OAHI was the sole determinant of change in BRS, HF power, and LF/HF ratio. CONCLUSIONS: Improvement in SDB was associated with improved BP control, regardless if SDB was treated or spontaneously resolved four years after initial diagnosis. Our findings highlight the importance of monitoring children to ensure improvement of SDB and reduce the risk for cardiovascular morbidity in the future. PMID- 24239498 TI - Objectively measured sleep duration and hyperglycemia in pregnancy. AB - OBJECTIVE: Our primary purpose was to assess the impact of objectively measured nighttime sleep duration on gestational glucose tolerance. We additionally examined associations of objectively measured daytime sleep duration and nap frequency on maternal glycemic control. METHODS: Sixty-three urban, low-income, pregnant women wore wrist actigraphs for an average of 6 full days in mid pregnancy prior to screening for hyperglycemia using the 1-h oral glucose tolerance test (OGTT). Correlations of nighttime and daytime sleep durations with 1-h OGTT values were analyzed. Multivariable logistic regression was used to evaluate independent associations between sleep parameters and hyperglycemia, defined as 1-h OGTT values >=130 mg/dL. RESULTS: Mean nighttime sleep duration was 6.9+/-0.9 h which was inversely correlated with 1-h OGTT values (r=-0.28, P=.03). Shorter nighttime sleep was associated with hyperglycemia, even after controlling for age and body mass index (adjusted odds ratio [OR], 0.2 [95% confidence interval {CI}, 0.1-0.8]). There were no associations of daytime sleep duration and nap frequency with 1-h OGTT values or hyperglycemia. CONCLUSIONS: Using objective measures of maternal sleep time, we found that women with shorter nighttime sleep durations had an increased risk for gestational hyperglycemia. Larger prospective studies are needed to confirm our negative daytime sleep findings. PMID- 24239500 TI - A review of bioeffects of static magnetic field on rodent models. AB - This review is aimed to summarize the experimental researches in the influences of static magnetic field on laboratory rodent models, reported by laboratory scientists, experimental technicians, clinical surgeons, animal veterinarians, and other researchers. Past studies suggested that static magnetic field-singly applied or used combined with other physical or chemical substances-significantly relieved some pains and ameliorated certain diseases in different organ systems, e.g. hypertension, osteoporosis, neuralgia, diabetes and leukemia etc. But on the other hand, some harmful events have also been observed in a number of investigations, from cellular level to fetal development. So exposure to static magnetic field might have dual effects on experimental rodent in various environments, viz. there are potentially therapeutic benefits, as well as adverse effects from it. The positive effect may relate to moderate intensities, while negative influence seems to be in connection with acute strong static magnetic fields. In addition, different orientations of static magnetic field exert different degrees of impact. Thus, the bioeffects of static magnetic field exposure on mice/rats depend on magnetic field intensities, durations and directions, though the exactly relationship between them is still vague. Further researches need to perform with appropriate methodologies, ingenious designs repeatedly and systemically, not only in animal models, but also in human volunteers and patients. PMID- 24239501 TI - The effects of metamaterial on electromagnetic fields absorption characteristics of human eye tissues. AB - The interaction of a dipole antenna with a human eye model in the presence of a metamaterial is investigated in this paper. The finite difference time domain (FDTD) method with convolutional perfectly matched layer (CPML) formulation have been used. A three-dimensional anatomical model of the human eye with resolution of 1.25 mm * 1.25 mm * 1.25 mm was used in this study. The dipole antenna was driven by modulated Gaussian pulse and the numerical study is performed with dipole operating at 900 MHz. The analysis has been done by varying the size and value of electric permittivity of the metamaterial. By normalizing the peak SAR (1 g and 10 g) to 1 W for all examined cases, we observed how the SAR values are not affected by the different permittivity values with the size of the metamaterial kept fixed. PMID- 24239499 TI - Associations of self-reported and actigraphy-assessed sleep characteristics with body mass index and waist circumference in adults: moderation by gender. AB - OBJECTIVES: Self-reported sleep duration has been linked to body mass index (BMI) and waist circumference in previous work; however, data regarding if these associations are stronger in men or women have been mixed, and few studies have objectively measured sleep. We investigated self-reported and actigraphy-assessed sleep characteristics in relation to BMI and waist circumference and examined the extent to which these associations differ by gender. DESIGN: Archived cross sectional data collected from 2004 to 2006 from the National Survey of Midlife Development in the United States (MIDUS) Biomarkers Study were used. Participants included 1248 adults (43% men) who reported their habitual sleep duration, and a subset of participants (N=441; 40% men) who underwent seven nights of wrist actigraphy. RESULTS: Self-reported total sleep time (TST), actigraphy-assessed TST, and actigraphy-assessed sleep efficiency (SE) were inversely associated with BMI in the full sample of both men and women. Gender moderated associations between actigraphy assessments of sleep and anthropometric variables; however, TST and SE were related to BMI and waist circumference in women only. Associations between sleep and waist circumference were independent of BMI. CONCLUSIONS: Sleep duration and sleep continuity are associated with body weight and distribution of body fat, but these associations were stronger or were only present in women. PMID- 24239502 TI - Functions and roles of proteins: diabetes as a paradigm. AB - Molecular and cellular biology has moved towards complete and accurate knowledge of how molecules behave in space and time. Protein is considered as the primary group of molecules responsible for mediating most physiological processes. Changes in the levels of proteins may lead to the altered function and are responsible for many diseases. This review provides a partial molecular explanation of biological force-ratio generation that may act to split protein into branches, and shows molecular functional divergence. Developing a non reductionist theory of the cellular function in medicine is clearly not sufficient. Finding effective parameters of the models by characterizing molecular interactions becomes necessary. Protein interactivity and stability provides a basis for an integrated understanding of pathologies such diabetes. One example of how a mechanistic analysis of such physiological processes can be of value is the time-delay between mRNA and translation that can act as a fork allowing a slowdown in gene expression. PMID- 24239503 TI - Will food-handling time influence agonistic behaviour in sub-adult common ravens (Corvus corax)? AB - Discovering a food source may invoke either competition or cooperation, depending on many factors such as divisibility and accessibility. We experimentally investigated the influence of effort to procure food on the tolerance towards others during feeding. Nine sub-adult captive ravens were tested in different foraging contexts that differed in foraging effort, namely three string-pulling conditions and two without pulling requirement. We expected that the effort to gain access to food would positively affect the tolerance towards others at feeding. As predicted, we found fewer agonistic interactions, fewer displacements of subordinates from food and prolonged feeding bouts in the three string-pulling conditions compared to the two conditions when no pulling was involved. Further, in the string pulling tasks interactions occurred mostly on the perch before pulling and only rarely was pulling interrupted by agonistic interactions. The rate of interactions did not change over trials. Our data suggests that perceived effort influences social behaviour. PMID- 24239504 TI - An eye for beauty: lateralized visual stimulation of courtship behavior and mate preferences in male zebra finches, Taeniopygia guttata. AB - Research on intersexual selection focuses on traits that have evolved for attracting mates and the consequences of mate choice. However, little is known about the cognitive and neural mechanisms that allow choosers to discriminate among potential mates and express an attraction to specific traits. Preferential use of the right eye during lateral displays in zebra finches, and lateralized expression of intermediate early genes in the left hemisphere during courtship led us to hypothesize that: (1) visual information from each eye differentially mediates courtship responses to potential mates; and (2) the ability to discriminate among mates and prefer certain mates over others is lateralized in the right eye/left hemisphere system of zebra finch brains. First, we exposed male zebra finches to females when using left, right or both eyes. Males courted more when the right eye was available than when only the left eye was used. Secondly, male preference for females - using beak color to indicate female quality - was tested. Right-eyed and binocular males associated with and courted orange-beaked more than gray-beaked females; whereas left-eyed males showed no preference. Lateral displays and eye use in male zebra finches increase their attractiveness and ability to assess female quality, potentially enhancing reproductive success. This article is part of a Special Issue entitled: CO3 2013. PMID- 24239505 TI - Is vitamin D deficiency a major global public health problem? AB - Vitamin D deficiency is a major public health problem worldwide in all age groups, even in those residing in countries with low latitude, where it was generally assumed that UV radiation was adequate enough to prevent this deficiency, and in industrialized countries, where vitamin D fortification has been implemented now for years. However, most countries are still lacking data, particularly population representative data, with very limited information in infants, children, adolescents and pregnant women. Since the number of recent publications is escalating, with a broadening of the geographic diversity, the objective of the present report was to conduct a more recent systematic review of global vitamin D status, with particular emphasis in at risk groups. A systematic review was conducted in PubMed/Medline in April-June 2013 to identify articles on vitamin D status worldwide published in the last 10 years in apparently healthy individuals. Only studies with vitamin D status prevalence were included. If available, the first source selected was population-based or representative samples studies. Clinical trials, case-control studies, case reports or series, reviews, validation studies, letters, editorials, or qualitative studies were excluded. A total of 103 articles were eligible and included in the present report. Maps were created for each age group, providing an updated overview of global vitamin D status. In areas with available data, the prevalence of low vitamin D status is a global problem in all age groups, in particular in girls and women from the Middle East. These maps also evidenced the regions with missing data for each specific population groups. There is striking lack of data in infants, children and adolescents worldwide, and in most countries of South America and Africa. In conclusion, vitamin D deficiency is a global public health problem in all age groups, particularly in those from the Middle East. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24239507 TI - Pathways and genes involved in steroid hormone metabolism in male pigs: a review and update. AB - This paper reviews state-of-the-art knowledge on steroid biosynthesis pathways in the pig and provides an updated characterization of the porcine genes involved in these pathways with particular focus on androgens, estrogens, and 16-androstenes. At least 21 different enzymes appear to be involved in these pathways in porcine tissues together with at least five cofactors. Until now, data on several porcine genes were scarce or confusing. We characterized the complete genomic and transcript sequences of the single porcine CYP11B gene. We analyzed the porcine AKR1 gene cluster and identified four AKR1C, one AKR1C like genes and one AKR1E2 gene. We provide evidence that porcine AKR1C genes are not orthologous to human AKR1C. A new nomenclature is thus needed for this gene family in the pig. Thirty two genes are now described: transcript (30+2 characterized in this study) and genomic (complete: 18+1 and partial: 12+1) sequences are identified. However, despite increasing knowledge on steroid metabolism in the pig, there is still no explanation of why porcine testes can produce androstenone and epiandrosterone, but not dihydrotestosterone (DHT), which is also a reduced steroid. PMID- 24239506 TI - Fundamentals of vitamin D hormone-regulated gene expression. AB - Initial research focused upon several known genetic targets provided early insight into the mechanism of action of the vitamin D hormone (1,25 dihydroxyvitamin D3 (1,25(OH)2D3)). Recently, however, a series of technical advances involving the coupling of chromatin immunoprecipitation (ChIP) to unbiased methodologies that initially involved tiled DNA microarrays (ChIP-chip analysis) and now Next Generation DNA Sequencing techniques (ChIP-seq analysis) has opened new avenues of research into the mechanisms through which 1,25(OH)2D3 regulates gene expression. In this review, we summarize briefly the results of this early work and then focus on more recent studies in which ChIP-chip and ChIP seq analyses have been used to explore the mechanisms of 1,25(OH)2D3 action on a genome-wide scale providing specific target genes as examples. The results of this work have advanced our understanding of the mechanisms involved at both genetic and epigenetic levels and have revealed a series of new principles through which the vitamin D hormone functions to control the expression of genes. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24239508 TI - Reciprocal role of vitamin D receptor on beta-catenin regulated keratinocyte proliferation and differentiation. AB - The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), suppresses the proliferation while promoting the differentiation of keratinocytes through the vitamin D receptor (VDR). beta-Catenin, on the other hand, promotes proliferation and blocks epidermal differentiation, although it stimulates hair follicle differentiation. In intestinal epithelia VDR binds beta-catenin and blocks its proliferative effects. In this study we investigated the role of 1,25(OH)2D3/VDR on beta-catenin regulated gene transcription during keratinocyte proliferation and differentiation. 1,25(OH)2D3 suppressed promoter reporter activity driven by synthetic and natural TCF/beta-catenin response elements. Over expression of VDR further suppressed these TCF/beta-catenin promoter activities. 1,25(OH)2D3 also suppressed the mRNA expression of the beta-catenin regulated gene Gli1 through VDR. These data were consistent with our previous observations that VDR silencing resulted in keratinocyte hyperproliferation with increased expression of Gli1 in vitro, whereas VDR null skin showed hyperproliferation in vivo. In contrast, 1,25(OH)2D3 induced expression of another beta-catenin regulated gene, PADI1, important for both epidermal and hair follicle differentiation. Deletion of VDR resulted in defects in hair differentiation in vivo, with decreased expression of beta-catenin regulated hair differentiation genes such as PADI1, hair keratin KRT31 and calcium binding protein S100a3. These genes possess vitamin D response elements (VDRE) adjacent to TCF/beta-catenin response elements and are regulated by both VDR and beta-catenin signaling. Therefore, we propose that VDR and beta-catenin interact reciprocally to promote VDR stimulation of genes involved with differentiation that contain both VDR and beta-catenin response elements while inhibiting beta-catenin stimulation of genes involved with proliferation. Thus the major finding of this study is that while 1,25(OH)2D3/VDR inhibits the actions of beta-catenin to promote keratinocyte proliferation, 1,25(OH)2D3/VDR promotes the ability of beta-catenin to stimulate hair follicle differentiation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24239509 TI - Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy. AB - Vision incapacitation and blindness associated with retinal degeneration affect millions of people worldwide. Cell based therapy and specifically transplantation of human adult bone marrow-derived stem cells (hBM-MSCs) present possible treatment strategy. Subretinal transplantation of human or rat BM-MSCs was shown previously to improve retinal function in Royal College Surgeons (RCS) rats. In those studies cells were transplanted via a transscleral-transchoroidal approach, creating a localized subretinal bleb. Limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection site. Here we describe a new surgical method for subretinal transplantation that facilitates uniform distribution of transplanted cells as a thin layer along most of the subretinal space. We assessed the therapeutic effect of hBM-MSCs on RCS rats when transplanted either subretinally or intravitreally. We also examined whether a second transplantation can prolong the therapeutic effect. A cell suspension of 2.5 * 10(6) cells in 5 MUl was injected subretinally or intravitreally in RCS rats at 28 days postnatal. In the subretinal group, hBM MSCs were transplanted posterior to the limbus in the superotemporal part of the eye through a longitudinal triangular scleral tunnel reaching the choroid. In the intravitreal group, the cells were injected into the superotemporal part of the vitreous cavity. In cross sections of subretinally transplanted eyes, removed 2 h following transplantation, hBM-MSCs were distributed as a near-homogenous thin layer along most of the subretinal space. In some animals the cells were also detected in the choroid. In the intravitreal injection group, hBM-MSCs were clustered in the vitreous cavity. Transplanted cells could be detected up to 2 weeks after transplantation but not at later time points. Retinal function and structure were assessed by electroretinogram (ERG) and histology analysis, respectively. Six weeks post transplantation, the mean maximal scotopic ERG b wave amplitude response recorded in RCS control eyes was 1.2 MUV. By contrast, in transplanted eyes mean responses of 56.4 MUV and 66.2 MUV were recorded in the intravitreally and subretinally transplanted eyes, respectively. In the subretinal group, retinal function was significantly higher in transplanted compared with control eyes up to 20 weeks following transplantation. By contrast, in the intravitreal group, rescue of retinal function persisted only up to 12 weeks following transplantation. Histological analysis revealed that 8 weeks following subretinal transplantation, the retinas of control eyes were dystrophic, with outer nuclear layer (ONL) containing a single cell layer. An extensive photoreceptor rescue was demonstrated in transplanted eyes at this time point, with 3-4 cell layers in the ONL along the entire retina. A second subretinal transplantation at 70 days postnatal did not enhance or prolong the therapeutic effect of hBM-MSCs. No immunosuppressants were used and long-term safety analysis demonstrated no gross or microscopic adverse effects. Taken together our findings suggest that transplantation of hBM-MSCs as a thin subretinal layer enhances the therapeutic effect and the safety of cell transplantation. PMID- 24239510 TI - Investigation of rat bone fracture healing using pulsed 1.5 MHz, 30 mW/cm(2) burst ultrasound--axial distance dependency. AB - This study investigated the effect of LIPUS on fracture healing when fractures were exposed to ultrasound at three axial distances: z=0 mm, 60 mm, and 130 mm. We applied LIPUS to rat fracture at these three axial distances mimicking the exposure condition of human fractures at different depths under the soft tissue. Measurement of LIPUS shows pressure variations in near field (nearby transducer); uniform profile was found beyond it (far field). We asked whether different positions of the fracture within the ultrasound field cause inconsistent biological effect during the healing process. Closed femoral fractured Sprague Dawley rats were randomized into control, near-field (0mm), mid-near field (60 mm) or far-field (130 mm) groups. Daily LIPUS treatment (plane, but apodized source, see details in the text; 2.2 cm in diameter; 1.5 MHz sine waves repeating at 1 kHz PRF; spatial average temporal average intensity, ISATA=30 mW/cm(2)) was given to fracture site at the three axial distances. Weekly radiographs and endpoint microCT, histomorphometry, and mechanical tests were performed. The results showed that the 130 mm group had the highest tissue mineral density; and significantly higher mechanical properties than control at week 4. The 60 mm and 0 mm groups had significantly higher (i.e. p<0.05) woven bone percentage than control group in radiological, microCT and histomorphometry measurements. In general, LIPUS at far field augmented callus mineralization and mechanical properties; while near field and mid-near field enhanced woven bone formation. Our results indicated the therapeutic effect of LIPUS is dependent on the axial distance of the ultrasound beam. Therefore, the depth of fracture under the soft tissue affects the biological effect of LIPUS. Clinicians have to be aware of the fracture depth when LIPUS is applied transcutaneously. PMID- 24239511 TI - Heat shock protein 27 phosphorylation is involved in epithelial cell apoptosis as well as epithelial migration during corneal epithelial wound healing. AB - We reported the expression of phosphorylated HSP27 during epithelial wound healing in murine corneas (Jain et al., 2012) in July of 2012. This in vivo investigation demonstrated that the expression levels of phosphorylated HSP27 were greater in wounded corneal epithelial cells than in unwounded controls and that the localization of phosphorylated HSP27 was in the basal and superficial epithelia three days following corneal epithelial wounding. We suggested that phosphorylated HSP27 had a role in the early phase of corneal epithelial wound healing. The purpose of this study was to investigate the exact role of heat shock protein 27 (HSP27) phosphorylation for the wound healing of cultured human corneal epithelial cells (HCECs). HSP27-specific siRNAs and control-siRNAs, with no known homologous targets in HCECs, were created. The cultured HCECs were divided into two groups: Scrambled control-siRNA-transfected group vs. HSP27 specific siRNA-transfected group. The scratch-induced directional wounding assay, Western blotting, using antibodies against non-phosphorylated and phosphorylated HSP27, non-phosphorylated and phosphorylated Akt, and Bcl-2-associated X protein (Bax), immunofluorescence staining to determine the filament actin, flow cytometry to measure apoptosis, and proliferation assay were performed to determine the role of HSP27. Western blot assay showed that the expression of phosphorylated HSP27 significantly increased at 5, 10, and 30 min after scratch wounding, compared with those in unwounded HCECs (all p < 0.05). Western blot assay also showed HSP27-specific siRNAs effectively blocked the expression of non phosphorylated HSP27. The HSP27-specific siRNA-transfected group had more Bax expression, less phosphorylated Akt expression, and less non-phosphorylated and phosphorylated HSP27 expression (all p < 0.05). The scratch-induced directional wounding assay showed the HSP27-specific siRNA-transfected group with a less migrating cell number than the control-siRNA-transfected group (p < 0.05). Immunofluorescence staining showed that reorganization of actin cytoskeleton prominently decreased in the HSP27-specific siRNA-transfected group, compared with the control siRNA-tranfected group. Flow cytometry revealed that the HSP27 specific siRNA-transfected group had more HCEC apoptosis. Proliferation assay showed no difference between the two groups. In conclusion, the role of HSP27 in corneal epithelial wound healing can be epithelial cell apoptosis, as well as epithelial migration. HSP27 is involved in HCEC migration by the reorganization of actin cytoskeleton. PMID- 24239512 TI - Primary non-Hodgkin's lymphoma of the common bile duct: A case report and literature review. AB - Hepatobiliary involvement by malignant lymphoma is usually a secondary manifestation of systemic disease, whereas primary non-Hodgkin's lymphoma of the extrahepatic biliary ducts is an extremely rare entity. We describe the case of a 57-year-old man who presented with an acute onset of obstructive jaundice and severe itching. Abdominal ultrasonography and computed tomography revealed intrahepatic and common hepatic ducts dilatation. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed a mid-common bile duct stricture. The patient was presumed to have cholangiocarcinoma of the common bile duct, and an en bloc resection of the tumor with Roux-en-Y hepaticojejunostomy and porta-hepatis lymph nodes dissection was performed. Histopathology and immunohistochemistry revealed a large B cell non Hodgkin's lymphoma. The patient received six cycles of combination chemotherapy using cyclophosphamide, vincristine, prednisone, and rituximab (CVP-R) protocol, and after a 5-year follow-up he is still in complete remission. We also reviewed the cases published from 1982 to 2012, highlighting the challenges in reaching a correct preoperative diagnosis and the treatment modalities used in each case. PMID- 24239513 TI - 12 month changes in dietary intake of adolescent girls attending schools in low income communities following the NEAT Girls cluster randomized controlled trial. AB - Poor dietary habits and obesity are more prevalent in lower socio-economic status (SES) communities. The NEAT Girls cluster randomized controlled trial was a school-based obesity prevention program targeting adolescent girls in low SES schools in NSW, Australia. The aim was to evaluate the 12-month impact of key nutrition program messages on dietary intake and food behaviors. Diet was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Individual foods were categorized into nutrient-dense or energy-dense, nutrient poor food groups and the percentage contribution to total energy intake calculated. Participants were aged 13.2+/-0.5years (n=330). There were no statistically significant group-by-time effects for dietary intake or food related behaviors, with 12-month trends suggesting more intervention group girls had improved water intakes (59% consuming?three glasses per day to 54% at 12 months vs. 50% to 61% in controls, p=0.052), with a greater proportion consuming < one sweetened beverage per day (24-41% vs. 34-37% in controls, p=0.057). Further research including more intensive nutrition intervention strategies are required to evaluate whether dietary intake in adolescent girls attending schools in low SES communities can be optimized. PMID- 24239514 TI - A pair of centromeric proteins mediates reproductive isolation in Drosophila species. AB - Speciation involves the reproductive isolation of natural populations due to the sterility or lethality of their hybrids. However, the molecular basis of hybrid lethality and the evolutionary driving forces that provoke it remain largely elusive. The hybrid male rescue (Hmr) and the lethal hybrid rescue (Lhr) genes serve as a model to study speciation in Drosophilids because their interaction causes lethality in male hybrid offspring. Here, we show that HMR and LHR form a centromeric complex necessary for proper chromosome segregation. We find that the Hmr expression level is substantially higher in Drosophila melanogaster, whereas Lhr expression levels are increased in Drosophila simulans. The resulting elevated amount of HMR/LHR complex in hybrids results in an extensive mislocalization of the complex, an interference with the regulation of transposable elements, and an impairment of cell proliferation. Our findings provide evidence for a major role of centromere divergence in the generation of biodiversity. PMID- 24239515 TI - miR-219 regulates neural precursor differentiation by direct inhibition of apical par polarity proteins. AB - Asymmetric self-renewing division of neural precursors is essential for brain development. Partitioning-defective (Par) proteins promote self-renewal, and their asymmetric distribution provides a mechanism for asymmetric division. Near the end of neural development, most asymmetric division ends and precursors differentiate. This correlates with Par protein disappearance, but mechanisms that cause downregulation are unknown. MicroRNAs can promote precursor differentiation but have not been linked to Par protein regulation. We tested a hypothesis that microRNA miR-219 promotes precursor differentiation by inhibiting Par proteins. Neural precursors in zebrafish larvae lacking miR-219 function retained apical proteins, remained in the cell cycle, and failed to differentiate. miR-219 inhibited expression via target sites within the 3' untranslated sequence of pard3 and prkci mRNAs, which encode Par proteins, and blocking miR-219 access to these sites phenocopied loss of miR-219 function. We propose that negative regulation of Par protein expression by miR-219 promotes cell-cycle exit and differentiation. PMID- 24239516 TI - Endovascular treatment of distal intracranial aneurysms with Onyx 18/34. AB - OBJECTIVE: Surgical clipping and coil embolization of distally located intracranial aneurysms can be challenging. The goal of this study was to assess the feasibility, safety and efficacy of treatment of distal aneurysms with the liquid embolic agent Onyx 18/34. METHODS: Sixteen patients were treated with Onyx 18/34 for distally located aneurysms in our institution between March 2009 and September 2012. The technique consists of occluding the aneurysm as well as the parent vessel at the level of aneurysm with Onyx 18 or 34. Candidates for this treatment were patients with distal aneurysms including mycotic aneurysms, dissecting aneurysms, and pseudoaneurysms in which coiling was considered impossible. RESULTS: Of the 16 patients, 12 presented with subarachnoid and/or intracerebral hemorrhage. Median aneurysm size was 4.6mm. Aneurysm locations were as follows: Posterior inferior cerebellar artery (n=5), distal anterior inferior cerebellar artery (n=3), distal pericallosal (n=3), distal anterior cerebral artery (n=3), lenticulostriate artery (n=1), and anterior ethmoidal artery (n=1). There were 4 mycotic aneurysms. Complete aneurysm obliteration was achieved in all 6 patients with available angiographic follow-up. There was only 1 (6.3%) symptomatic complication in the series. There were no instances of reflux or accidental migration of embolic material. Favorable outcomes were noted in 82% of patients at discharge. Two patients with mycotic aneurysms died from cardiac complications of endocarditis. No aneurysm recanalization or rehemorrhage were seen. CONCLUSION: Parent vessel trapping with Onyx 18/34 offers a simple, safe, and effective means of achieving obliteration of distal challenging aneurysms. PMID- 24239517 TI - Endovascular treatment of acute carotid occlusion. AB - OBJECTIVES: Acute cervical carotid occlusion is one of the most challenging scenarios encountered in endovascular stroke treatment. PATIENTS AND METHODS: A retrospective analysis of 11 consecutive non-dissection stroke patients with concomitant cervical carotid and intracranial occlusion treated with intraarterial (IA) mechanical thrombectomy and/or pharmacologic thrombolysis over five years at two academic hospitals was performed. Data was analyzed using Fisher's exact test. RESULTS: Patients included 3 females and 8 males. Average age was 64.7 years (range 30-94 years). All patients had both cervical carotid and intracranial occlusions. Intracranial occlusion involved the internal carotid artery in 7 patients and the middle cerebral artery in 4 patients. All of the patients received intracranial IA Tissue Plasminogen Activator (tPA). Six patients received carotid stents for cervical occlusion as part of their treatment. Five patients received only IA tPA via collateral circulation. Of the patients receiving stents, 5 of 6 (83.3%) had successful recanalization (Thrombolysis in Cerebral Ischemia 2b or 3 flow). Only 1 of 5 (20%) patients who did not receive stents prior to intracranial treatment had successful recanalization. The difference in recanalization rates approached statistical significance (p=.08). There were 4 total in-hospital mortalities: 2 in the group that received stents prior to thrombolysis and 2 in the non-stent group. There were 2 clinically significant hemorrhages in the study, both in the stent group. CONCLUSIONS: Revascularization of the cervical carotid occlusion prior to treatment of the intracranial occlusion led to increased rates of recanalization in patients with tandem extracranial and intracranial occlusions. Whether a clinical benefit can be consistently derived likely relies on other factors, including the evaluation of cerebral perfusion. PMID- 24239518 TI - Significance of immunity against lung pathogens in untreated Parkinson's disease. PMID- 24239519 TI - Unplanned readmissions after vascular surgery. AB - OBJECTIVE: Existing literature on readmission after vascular surgery is limited. The upcoming reduction in Medicare reimbursement for institutions with high readmission rates mandates an accurate understanding of this issue. In this study, we characterize the frequency and causes of 30-day unplanned readmissions after elective vascular surgery. METHODS: Patients who underwent elective carotid endarterectomy (CEA), endovascular aortic repair (EVAR), open abdominal aortic aneurysm (oAAA) repair, or infrainguinal bypass grafting (BPG) were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2011 database (n = 11,246). Multivariable logistic regression was used to determine variables that contributed to 30-day unplanned readmissions for each surgery type. RESULTS: The unadjusted unplanned readmission rates after the four vascular procedures ranged from 6.5% for CEA to 15.7% for BPG. In multivariable analyses, patient comorbidities were associated with unplanned readmission after BPG and CEA (P < .05), whereas postoperative complications were more consistently associated with unplanned readmission after EVAR and oAAA repair (P < .05). For all procedures, complications leading to readmission developed more frequently after discharge. Thirty-day mortality was significantly higher in readmitted patients after BPG (1.9% vs 0.3%), EVAR (3.9% vs 0.1%), and CEA (2.2% vs 0.2%; P < .001 for each), but not after oAAA repair. CONCLUSIONS: Select comorbidities and postoperative complications contribute to unplanned readmissions after vascular surgery. The characteristics of readmitted patients vary with the type of procedure. Interventions designed to mitigate these factors have the potential to reduce unplanned readmissions but likely need to vary with the type of vascular treatment. PMID- 24239520 TI - First implantation of Gore Hybrid Vascular Graft in the right vertebral artery for cerebral debranching in a patient with Loeys-Dietz syndrome. AB - A 53-year-old woman with Loeys-Dietz syndrome developed progressive subclavian artery aneurysm and common carotid artery dissection. She was treated successfully by plugging and coiling of the subclavian aneurysm and its side branches after combined cervical debranching using standard carotid-axillary bypass and Gore Hybrid Vascular Graft for vertebral revascularization. Follow-up control (4 weeks) documented patent debranching, and only minimal residual flow in the subclavian aneurysm. The described off-label use for sutureless cerebral revascularisation of the vertebral artery might be a fast, simple, and reliable solution for cervical debranching in selective challenging patients. Further studies are necessary to evaluate side effects and durability. PMID- 24239521 TI - Endovascular therapy for long-segment atherosclerotic aortoiliac occlusion. AB - OBJECTIVE: This retrospective nonrandomized study investigated the outcomes of endovascular therapy for long-segment atherosclerotic aortoiliac occlusion. METHODS: From May 2008 to January 2013, 20 patients (one woman and 19 men; mean age, 66.1 years; range, 43-89 years) underwent stent implantation, with or without catheter-directed thrombolysis (CDT), for long-segment aortoiliac occlusion (>10 mm). RESULTS: The technical success rate was 95% (19 of 20). No in hospital mortality was recorded. Aortic thrombus was successfully eliminated with CDT in four patients before percutaneous transluminal angioplasty (PTA) and stenting. Retroperitoneal hemorrhage occurred in one patient, who refused further endovascular surgery. Another 15 patients were treated with PTA and stenting. Postoperative ankle-brachial indexes increased significantly from preoperative values (P < .05). Seventeen patients showed clinical improvement from baseline by an average of 2.5 Rutherford categories. The mean follow-up interval was 17.6 months (range, 4-39 months). The primary patency rates were 93.3% +/- 6.4% at 6 months, 83% +/- 11.3% at 18 months, and 66.4% +/- 17.4% at 24 months. CONCLUSIONS: Through brachial and femoral artery puncture, PTA, stenting, and CDT, endovascular therapy is feasible for complete long-segment infrarenal aortic occlusion, with lower complication rates and favorable midterm patency. PMID- 24239522 TI - A noninterventional management approach to endovascular coil migration into the sigmoid colon. AB - A 75-year-old man underwent endovascular treatment of a right internal iliac artery (IIA) aneurysm by placing coils in the distal IIA and occluding the inflow with a common iliac artery-to-external iliac artery stent graft. Surveillance computed tomography angiography discovered migration of an endovascular coil from the thrombosed right IIA into the sigmoid colon. Subsequent serial imaging demonstrated uncomplicated extracorporeal passage of the coil. We review the relevant literature and treatment rationale. PMID- 24239523 TI - Genotoxicity assessment of some cosmetic and food additives. AB - alpha-Hexylcinnamaldehyde (HCA) and p-tert-butyl-alpha-methylhydrocinnamic aldehyde (BMHCA) are synthetic aldehydes, characterized by a typical floral scent, which makes them suitable to be used as fragrances in personal care (perfumes, creams, shampoos, etc.) and household products, and as flavouring additives in food and pharmaceutical industry. The aldehydic structure suggests the need for a safety assessment for these compounds. Here, HCA and BMHCA were evaluated for their potential genotoxic risk, both at gene level (frameshift or base-substitution mutations) by the bacterial reverse mutation assay (Ames test), and at chromosomal level (clastogenicity and aneuploidy) by the micronucleus test. In order to evaluate a primary and repairable DNA damage, the comet assay has been also included. In spite of their potential hazardous chemical structure, a lack of mutagenicity was observed for both compounds in all bacterial strains tested, also in presence of the exogenous metabolic activator, showing that no genotoxic derivatives were produced by CYP450-mediated biotransformations. Neither genotoxicity at chromosomal level (i.e. clastogenicity or aneuploidy) nor single-strand breaks were observed. These findings will be useful in further assessing the safety of HCA and BMHCA as either flavour or fragrance chemicals. PMID- 24239524 TI - A single-round multiplex PCR assay for the identification of Anopheles minimus related species infected with Plasmodium falciparum and Plasmodium vivax. AB - This study aimed to develop a single-round multiplex PCR method for the identification of Anopheles minimus complex (An. minimus and Anopheles harrisoni) and Anopheles aconitus subgroup (An. aconitus and Anopheles varuna), and for the simultaneous detection of Plasmodium falciparum and Plasmodium vivax in these vectors. Five primers were created for a single-round multiplex PCR assay to identify four anopheline mosquitoes combined with three Plasmodium primers for the detection of P. falciparum and P. vivax in vectors. The four species of anopheline vectors and two Plasmodium species, P. falciparum and P. vivax, could be identified by the combination of eight primers in the single-round multiplex PCR assay. The amplified species-specific products were 380bp for An. minimus, 180bp for An. harrisoni, 150bp for An. aconitus, 310bp for An. varuna, 276bp for P. falciparum, and 300bp for P. vivax. The sensitivities were 0.5pg/MUl (25sporozoites/MUl) for P. falciparum DNA and between 0.5 and 5pg/MUl (25 250sporozoites/MUl) for P. vivax DNA. Furthermore, this developed method could be used to identify field caught An. minimus complex, An. aconitus subgroup from Thailand and Lao PDR. Also, it was successfully used to identify the species An. minimus, An. harrisoni, An. aconitus and An. varuna and to detect and identify P. falciparum and P. vivax in caught anopheline mosquitoes. The sensitivity of this method was high for simultaneous detection of P. falciparum and P. vivax in anopheline mosquitoes. PMID- 24239525 TI - The impact of Model for End-Stage Liver Disease-Na in predicting morbidity and mortality following elective colon cancer surgery irrespective of underlying liver disease. AB - BACKGROUND: The Model for End-Stage Liver Disease Sodium Model (MELD-Na) is a validated scoring system that uses bilirubin, international normalized ratio, serum creatinine, and sodium to predict mortality in cirrhotic patients awaiting liver transplantation. The aim of this study was to identify the utility of MELD Na to predict patient outcomes, with and without liver disease, after elective colon cancer surgery. METHODS: A review of the American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2010) was conducted to calculate risk-adjusted 30-day outcomes using regression modeling. RESULTS: A total of 10,842 patients (mean age, 68 years; 51% women) were included. MELD-Na scores were higher in men (10.2 vs 9.1, P < .001) and in open procedures (9.9 vs 9.1, P < .001). The overall complication and mortality rates were 26.3% and 3.3%, respectively. Incremental increases in MELD-Na score correlated with a 1.2% increase in mortality and a 1.1% increase in complications. On multivariate analysis, complications increased with MELD-Na score (odds ratio [OR], 1.05 per 1 point increase; 95% confidence interval [CI], 1.038 to 1.066). MELD-Na score was also associated with increased mortality (OR, 1.13; 95% CI, 1.1 to 1.16), along with ascites (OR, 5.7; 95% CI, 3.7 to 8.8) and corticosteroids (OR, 2.1; 95% CI, 1.3 to 3.3). CONCLUSIONS: Elevated preoperative MELD-Na score is significantly associated with worse outcomes after elective resection for colon cancer. PMID- 24239526 TI - Pilonidal disease in a military population: how far have we really come? AB - BACKGROUND: Pilonidal disease (PD) has a long connection with military personnel, even nicknamed "jeep disease" during World War II. The aim of this study was to identify factors associated with recurrence and complications after surgery in a military population. METHODS: A retrospective cohort analysis of operative therapy for PD at a single institution from 2005 to 2011 was conducted. Patient demographics, disease characteristics, and surgical methods were assessed for the primary outcomes of recurrence and morbidity. RESULTS: A total of 151 patients with PD were identified, who underwent excision (45.7%), excision with primary closure (29.8%), and incision and drainage (9.9%). Overall recurrence and morbidity rates were 27.2% and 34.4%, respectively. Black race, chronic disease, wound infection, and infection and drainage were associated with recurrence (P < .05), and excision with primary closure was associated with increased complications (P < .001). CONCLUSIONS: PD remains a significant source of morbidity and recurrence among military personnel. Certain patient-related and disease-related factors portend a worse prognosis, with black race and operative method the strongest predictors of outcomes. PMID- 24239527 TI - Cost and logistics of implementing a tissue-based American College of Surgeons/Association of Program Directors in Surgery surgical skills curriculum for general surgery residents of all clinical years. AB - BACKGROUND: The cost and logistics of deploying the American College of Surgeons (ACS)/Association of Program Directors in Surgery (APDS) National Technical Skills Curriculum across all training years are not known. This information is essential for residency programs choosing to adopt similar curricula. METHODS: A task force evaluated the authors' institution's existing simulation curriculum and enhanced it by implementing the ACS/APDS modules. A 35-module curriculum was administered to 35 general surgery residents across all 5 clinical years. The costs and logistics were noted, and resident satisfaction was assessed. RESULTS: The annual operational cost was $110,300 ($3,150 per resident). Cost per module, per resident was $940 for the cadaveric module compared with $220 and $240 for dry simulation and animal tissue-based modules, respectively. Resident satisfaction improved from 2.45 to 4.78 on a 5-point, Likert-type scale after implementing the ACS/APDS modules. CONCLUSIONS: The ACS/APDS skills curriculum was implemented successfully across all clinical years. Cadaveric modules were the most expensive. Animal and dry simulation modules were equivalent in cost. The addition of tissue-based modules was associated with high satisfaction. PMID- 24239528 TI - Faculty and resident evaluations of medical students on a surgery clerkship correlate poorly with standardized exam scores. AB - BACKGROUND: The clinical knowledge of medical students on a surgery clerkship is routinely assessed via subjective evaluations from faculty members and residents. Interpretation of these ratings should ideally be valid and reliable. However, prior literature has questioned the correlation between subjective and objective components when assessing students' clinical knowledge. METHODS: Retrospective cross-sectional data were collected from medical student records at The Johns Hopkins University School of Medicine from July 2009 through June 2011. Surgical faculty members and residents rated students' clinical knowledge on a 5-point, Likert-type scale. Interrater reliability was assessed using intraclass correlation coefficients for students with >=4 attending surgeon evaluations (n = 216) and >=4 resident evaluations (n = 207). Convergent validity was assessed by correlating average evaluation ratings with scores on the National Board of Medical Examiners (NBME) clinical subject examination for surgery. Average resident and attending surgeon ratings were also compared by NBME quartile using analysis of variance. RESULTS: There were high degrees of reliability for resident ratings (intraclass correlation coefficient, .81) and attending surgeon ratings (intraclass correlation coefficient, .76). Resident and attending surgeon ratings shared a moderate degree of variance (19%). However, average resident ratings and average attending surgeon ratings shared a small degree of variance with NBME surgery examination scores (rho(2) <= .09). When ratings were compared among NBME quartile groups, the only significant difference was for residents' ratings of students with the lower 25th percentile of scores compared with the top 25th percentile of scores (P = .007). CONCLUSIONS: Although high interrater reliability suggests that attending surgeons and residents rate students with consistency, the lack of convergent validity suggests that these ratings may not be reflective of actual clinical knowledge. Both faculty members and residents may benefit from training in knowledge assessment, which will likely increase opportunities to recognize deficiencies and make student evaluation a more valuable tool. PMID- 24239529 TI - Development of an evidence-based curriculum for training of ward-based surgical care. AB - BACKGROUND: Ward-based care of surgical patients is a complex and variable process, centered on the surgical ward round (WR). The authors describe the development of an evidence-based curriculum to improve ward-based care in the form of surgical WRs. METHODS: A modular, simulation-based curriculum was developed according to validated methods, incorporating the most recent evidence in the design of each educational module. RESULTS: A predevelopmental analysis questionnaire identified themes of patient assessment and management, communication skills, and teamwork as areas to be addressed. Curricular development incorporated knowledge and confidence assessment, lecture-based teaching, and simulated WR, followed by individualized assessment, debriefing, and feedback. Each module is evidence based and assesses trainees using validated tools. CONCLUSIONS: A comprehensive and cost-effective simulation-based curriculum, developed according to a validated framework, has been developed for surgical WRs and ward-based care. This may improve trainees' WR performance, improving patient care and surgical outcomes in turn. PMID- 24239530 TI - Improved perioperative and short-term outcomes of robotic versus conventional laparoscopic colorectal operations. AB - BACKGROUND: Robotic assistance may offer unique advantages over conventional laparoscopy in colorectal operations. METHODS: This prospective observational study compared operative measures and postoperative outcomes between laparoscopic and robotic abdominal and pelvic resections for benign and malignant disease. RESULTS: From 2005 through 2012, 200 (58%) laparoscopic and 144 (42%) robotic operations were performed by a single surgeon. After adjustment for differences in demographics and disease processes using propensity score matching, all laparoscopic operations had a significantly shorter operative time (P < .01), laparoscopic left colectomies had a longer length of hospital stay (2009 and 2010: 6.5 vs 3.6 days, P = .01); and laparoscopic right colectomies had a higher risk for overall complications (P = .03) and postoperative ileus (P = .04). There were no significant differences in the outcomes of pelvic operations (P = .15). CONCLUSIONS: Compared with conventional laparoscopy, some types of robotic assisted colorectal operations may offer advantages regarding postoperative length of stay and perioperative complications. PMID- 24239531 TI - A framework for professionalism in surgery: what is important to medical students? AB - BACKGROUND: The purposes of this study were to develop a comprehensive framework for professionalism in surgery and to determine which attributes are most valued by medical students. METHODS: A framework for professionalism in surgery, consisting of 11 attribute categories, was developed. All 3rd-year medical students (n = 168) participated in a focus group and completed a questionnaire regarding their perceptions about professionalism. Students' responses were transcribed verbatim, coded, and assigned attribute categories. RESULTS: Students rated respect as the most important attribute of professionalism (56%), followed by altruism (21%) and interpersonal skills (8%). Fifty-three percent of students witnessed unprofessional behavior among faculty members while on the surgical clerkship. Of these incidents, 74% were related to respect, 28% to practice improvement, and 1% to altruism. CONCLUSIONS: Respect was rated as the single most important characteristic of professionalism and was the attribute with the most witnessed violations. PMID- 24239532 TI - Combination therapy with nitazoxanide and amphotericin B, Glucantime(r), miltefosine and sitamaquine against Leishmania (Leishmania) infantum intracellular amastigotes. AB - Leishmaniasis is a neglected disease that affects poorest population mainly in developing countries, representing one of the major causes of mortality and morbidity. Therefore, efforts to find new chemotherapeutics for leishmaniasis remain a priority. Previous reports demonstrated the in vitro and in vivo antileishmanial activity of nitazoxanide, an antiprotozoan agent used in the treatment of infectious diarrhea. The present work was carried out to determine the effect of nitazoxanide in combination with current antileishmanial drugs. Mouse peritoneal macrophages were infected with Leishmania (Leishmania) infantum amastigotes in order to calculate the 50% and 90% inhibitory concentration values. Drug interactions were assessed with fixed ratio isobologram method and fractional inhibitory concentrations (FIC50 and FIC90); sum of FIC (SigmaFIC50 and SigmaFIC90) and overall mean SigmaFIC (xSigmaFIC50 and xSigmaFIC90) were calculated for each combination. The nature of interactions was classified according to the xSigmaFIC50 and xSigmaFIC90. The combination between nitazoxanide and amphotericin B, Glucantime((r)), miltefosine and sitamaquine showed xSigmaFIC50 values of 1.13, 0.83, 1.06 and 0.94, respectively, indicating additive interaction. Considering the in vitro activity of nitazoxanide and the obtained results, further in vivo studies may be considered to evaluate possible drug interactions in visceral leishmaniasis. PMID- 24239533 TI - HLA incompatible combined liver-kidney transplantation: dynamics of antibody modulation revealed by a novel approach to HLA antibody characterisation. AB - This case report confirms the utility of simultaneous liver transplantation in allowing successful kidney transplantation in the face of preformed, high levels of DSA, which would under normal circumstances be associated with hyperacute rejection and kidney graft failure. Antibody characterisation in terms of epitope specificity is more accurate and informative than antibodies described as "antigen-specific" and we suggest a method for identifying and tracking these antibodies; i.e. follow the epitope reaction not the antigen reactions. We consider that this will give a better insight into the behaviour and pathogenicity of HLA-specific sera. In the case presented here this approach has revealed some novel features of the post transplant antibody response in a sensitised recipient. These illustrate three phenomena which challenge current dogmas; an early resynthesis of DSA does not necessarily cause AMR, high levels of DSA can spontaneously modulate, and measurement of antibodies in terms of antigen specificity can give misleading results. PMID- 24239534 TI - Development of inhibitors in the ubiquitination cascade. AB - The ubiquitin proteasome system (UPS) is essential in regulating myriad aspects of protein functions. It is therefore a fundamentally important regulatory mechanism that impacts most if not all aspects of cellular processes. Indeed, malfunction of UPS components is implicated in human diseases such as neurodegenerative and immunological disorders and many cancers. The success of proteasome inhibitors in cancer therapy suggests that modulating enzymes in the ubiquitination cascade would be clinically important for therapeutic benefits. In this review, we summarize advances in developing inhibitors of a variety of UPS components. In particular, we highlight recent work done on the protein engineering of ubiquitin as modulators of the UPS, a novel approach that may shed light on innovative drug discovery in the future. PMID- 24239535 TI - Anticalins: exploiting a non-Ig scaffold with hypervariable loops for the engineering of binding proteins. AB - Antibodies, which can recognize a plethora of possible antigens, have been considered as a paradigm of protein engineering performed by nature itself. Lipocalins constitute a distinct family of proteins with functions in ligand binding and transport that occur in many organisms, including man. Like antibodies, lipocalins exhibit a structurally conserved framework - a beta-barrel with an attached alpha-helix - which supports four structurally hypervariable loops forming a cup-shaped binding site. Thus, lipocalins offer an ideal platform for protein engineering to generate novel binding reagents. Using recombinant/synthetic DNA technology and methods of combinatorial library selection, 'Anticalins' with prescribed target specificities can be easily generated. Anticalins with picomolar affinities have been developed for three classes of ligands having relevance in basic research and/or medical application: small molecules, peptides, and proteinaceous signalling molecules as well as cell surface receptors. Anticalins derived from human lipocalins have already reached the clinical trial stage. Due to their very small size and simple composition of a single polypeptide chain, which also facilitates the construction of bifunctional fusion proteins, Anticalins promise benefits as a next class of biopharmaceuticals. PMID- 24239536 TI - Heterogeneity of koala retrovirus isolates. AB - Koala retrovirus (KoRV) is a gammaretrovirus which may induce immune suppression, leukemia and lymphoma in koalas. Currently three KoRV subgroups (A, B, and J) have been reported. Our phylogenetic analysis suggests that KoRV-B and KoRV-J should be classified as the same subgroup. In long terminal repeat (LTR), a KoRV B isolate has four 17 bp tandem repeats named direct repeat (DR)-1, while a KoRV J isolate (strain OJ-4) has three 37 bp tandem repeats named DR-2. We also found that the promoter activity of the KoRV-J strain OJ-4 is stronger than that of original KoRV-A, suggesting that KoRV-J may replicate more efficiently than KoRV A. PMID- 24239537 TI - Erythroid differentiation is augmented in Reelin-deficient K562 cells and homozygous reeler mice. AB - Reelin is an extracellular glycoprotein that is highly conserved in mammals. In addition to its expression in the nervous system, Reelin is present in erythroid cells but its function there is unknown. We report in this study that Reelin is up-regulated during erythroid differentiation of human erythroleukemic K562 cells and is expressed in the erythroid progenitors of murine bone marrow. Reelin deficiency promotes erythroid differentiation of K562 cells and augments erythroid production in murine bone marrow. In accordance with these findings, Reelin deficiency attenuates AKT phosphorylation of the Ter119(+)CD71(+) erythroid progenitors and alters the cell number and frequency of the progenitors at different erythroid differentiation stages. A regulatory role of Reelin in erythroid differentiation is thus defined. PMID- 24239538 TI - A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein. AB - Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. PMID- 24239539 TI - Profiling the IgOme: meeting the challenge. AB - The entire repertoire of antibodies in our serum, the IgOme, is a historical record of our past experiences and a reflection of our immune status at any given moment. Understanding the dynamics of the IgOme and how the diversity and specificities of serum antibodies change in response to disease and maintenance of homeostasis can directly impact the ability to design and develop novel vaccines, diagnostics and therapeutics. Here we review both direct and indirect methodologies that are being developed to map the complexity and specificities of the antibodies in polyclonal serum - the IgOme. PMID- 24239540 TI - Fabrication of Phaeodactylum tricornutum extract-loaded gelatin nanofibrous mats exhibiting antimicrobial activity. AB - Microalgae have recently been recognized as a valuable resource for various applications. Phaeodactylum tricornutum is a diatom that lives in marine water and has an unusually high content of lipids. In this study, we added P. tricornutum into a gelatin dope solution to examine the effect of this diatom using electrospinning. The addition of P. tricornutum extracts increased the conductivity of the dope solution but had little effect on the viscosity. Due to the increased conductivity, the fiber diameter was reduced compared with the neat gelatin nanofiber. The loading of P. tricornutum extracts was confirmed using fluorescence microscopy, and the incorporation of lipids was detected through gas chromatography. The P. tricornutum-loaded nanofiber mat exhibited anti-microbial activity against Escherichia coli and multidrug-resistant Staphylococcus aureus (MRSA). The cell viability test showed that the P. tricornutum-loaded nanofiber has no cytotoxicity. We expect that this antimicrobial P. tricornutum-loaded gelatin nanofiber mat can be applied as a wound dressing. PMID- 24239541 TI - Preparation of p-nitrophenyl beta-l-arabinofuranoside as a substrate of beta-l arabinofuranosidase. AB - Synthesis of p-nitrophenyl beta-l-arabinofuranoside 1 as the substrate for novel beta-l-arabinofuranosidase has been achieved by using both our inter- and intra molecular glycosylation methodologies. Although the intermolecular glycosylation with l-Araf donors 3 and 4 resulted in a mixture of both alpha- and beta-isomers, NAP ether-mediated IAD with 3 and 6 afforded the desired beta-l-arabinofuranoside stereospecifically which was confirmed by NMR analysis on the (3)JH1-H2 coupling constant and (13)C chemical shift of C1. As expected, 1 has been revealed to be an efficient substrate in the biological study of a novel beta arabinofuranosidase such as HypBA1 with higher apparent affinity compared with other reported substrates. PMID- 24239542 TI - Biosynthesis of 2-O-D-glucopyranosyl-l-ascorbic acid from maltose by an engineered cyclodextrin glycosyltransferase from Paenibacillus macerans. AB - In this work, the specificity of cyclodextrin glycosyltransferase (CGTase) of Paenibacillus macerans towards maltose was improved by the site-saturation engineering of lysine 47, and the enzymatic synthesis of 2-O-d-glucopyranosyl-l ascorbic acid (AA-2G) with l-ascorbic acid and maltose as substrates was optimized. Compared to the AA-2G yield of the wild-type CGTase, that of the mutants K47F (lysine->phenylalanine), K47P (lysine->proline), and K47Y (lysine >tyrosine) was increased by 17.1%, 32.9%, and 21.1%, respectively. Under the optimal transformation conditions (pH 6.5, temperature 36 degrees C, the mass ratio of l-ascorbic acid to maltose 1:1), the highest AA-2G titer by the K47P reached 1.12g/L, which was 1.32-fold of that (0.85g/L) obtained by the wild-type CGTase. The reaction kinetics analysis confirmed the enhanced maltose specificity of the mutants K47F, K47P, and K47Y. It was also found that compared to the wild type CGTase, the three mutants had relatively lower cyclization activities and higher disproportionation activities, which was favorable for AA-2G synthesis. As revealed by the interaction structure model of CGTase with substrate, the enhancement of maltose specificity may be due to the removal of hydrogen bonding interactions between the side chain of residue 47 and the sugar at -3 subsite. The obtained mutant CGTases, especially the K47P, has a great potential in the large-scale production of AA-2G with maltose as a cheap and soluble substrate. PMID- 24239544 TI - Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells. AB - The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis. PMID- 24239543 TI - Protein engineering to target complement evasion in cancer. AB - The complement system is composed of soluble factors in plasma that enhance or "complement" immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors - one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in complement inhibitory factors are found on these cells. This review focuses on the classic complement pathway and the role of major complement inhibitory factors in cancer immune evasion as well as on how current protein engineering efforts are being employed to increase complement fixing or to reverse complement resistance leading to better therapeutic outcomes in oncology. Strategies discussed include engineering of antibodies to enhance complement fixation, antibodies that neutralize complement inhibitory proteins as well as engineered constructs that specifically target inhibition of the complement system. PMID- 24239545 TI - Conserved RNA cis-elements regulate alternative splicing of Lepidopteran doublesex. AB - Doublesex (dsx) is a downstream key regulator in insect sex determination pathway. In Drosophila, alternative splicing of Dm-dsx gene is sex-specifically regulated by transformer (tra), in which the functional TRA promotes female specific Dm-dsx. However, the sex determination pathway in Lepidoptera is not well understood; here we focused on alternative splicing of doublesex (dsx) in two agricultural pests, Asian corn borer (Ostrinia furnacalis) and cotton bollworm (Helicoverpa armigera), as well as the silkworm (Bombyx mori). More than a dozen new alternative splicing isoforms of dsx were found in the Lepidopteran females, which exist in all tested developmental stages and differentiated tissues. Alignment of mRNA and protein sequences of doublesex revealed high conservation of this gene in Lepidoptera. Strength analysis of splice sites revealed a weak 5' splice site at intron 3 in Lepidopteran dsx, which was experimentally confirmed. Furthermore, we identified highly conserved RNA sequences in the Lepidopteran dsx, including RNA elements I (14 nt), II (11 nt), III (26 nt), IV (17 nt), 3E-1 (8 nt) and 3E-2 (8 nt). The RNA elements III and IV were previously found in exon 4 of B. mori dsx and bound with Bm-PSI, which suppressed the inclusion of exons 3 & 4 into the male-specific Bm-dsx. Then we identified and analyzed the homologous genes of Bm-psi in the two Lepidopteran pests, which expressed at similar levels and exhibited a unique isoform in the males and females from each Lepidoptera. Importantly, mutagenesis of Bm-dsx mini genes and their expression in BmN cell line demonstrated that three RNA elements are involved in the female-specific alternative splicing of Bm-dsx. Mutations in the RNA cis-elements 3E-1 and 3E-2 resulted in decreased inclusion of exon 3 into the female-specific dsx mRNA, suggesting that these two elements would be exonic splicing enhancers that facilitate the recognition of the weak 5' splice site at intron 3 of Lepidopteran dsx. We propose that the 5' splice sites at intron 3 are weak, resulting in multiple alternative splicing events in intron 3 of female Lepidoptera dsx. Activation of the 5' splice site requires regulatory cis elements in exons 3 for female-specific splicing of Lepidoptera dsx. PMID- 24239546 TI - Suppression of Fas-mediated apoptosis via steric shielding by filovirus glycoproteins. AB - Apoptotic death of virus-infected cells is generally thought to be a defense mechanism to limit the spread of infectious virions by eliminating virus producing cells in host animals. On the other hand, several viruses have been shown to have anti-apoptotic mechanisms to facilitate efficient viral replication and transmission. In this study, we found that the filovirus glycoprotein (GP) expressed on cell surfaces formed a steric shield over the Fas molecule and that GP-expressing cells showed resistance to cell death induced by a Fas agonistic antibody. These results suggest that filovirus GP-mediated steric shielding may interfere with the Fas-induced apoptotic signal transduction in infected cells and serve as an immune evasion mechanism for filoviruses. PMID- 24239547 TI - Prediction of the interaction between spermidine and the G-G mismatch containing acceptor stem in tRNA(Ile): molecular modeling, density functional theory, and molecular dynamics study. AB - Polyamines, putrescine, spermidine (SPD), and spermine are closely linked to cell growth, and highly regulate the levels of transcription, translation and protein turnover. We propose that SPD stimulates the formation of Ile-tRNA(Ile) by inducing a selective structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Here, we provide insight into how SPD recognizes and stabilizes the G-G mismatch containing acceptor stem in tRNA(Ile) with molecular modeling (MM), density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The results of the MM and DFT calculations indicate that the negatively charged region of the G-G mismatch containing acceptor stem in tRNA(Ile) is preferentially recognized by positively charged SPD. In addition, MD simulations indicate that all of the positively charged amino groups of SPD under physiological conditions (N1(NH3(+)), N5(NH2(+)), and N10(NH3(+)) could form hydrogen bonds with tRNA(Ile) and trigger the SPD-induced stabilization and structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Thus, this approach should be useful for determining the preferential binding site and appropriate binding mode of polyamines on tRNA(Ile). PMID- 24239548 TI - Qualitative computational bioanalytics: assembly of viral channel-forming peptides around mono and divalent ions. AB - A fine-grained docking protocol was used to generate a bundle-like structure of the bitopic membrane protein Vpu from HIV-1. Vpu is a type I membrane protein with 81 amino acids. It is proposed that Vpu forms ion- and substrate-conducting bundles, which are located at the plasma membrane in the infected cell. The Vpu1 32 peptide that includes the transmembrane domain (TMD) is assembled into homo pentameric bundles around prepositioned Na, K, Ca or Cl ions. For bundles with the lowest energy, the TMDs generate a hydrophobic pore. Bundles in which Ser-24 faces the pore have higher energy. The tilt of the helices in the lowest energy bundles is larger than bundles with serines facing the pore. Left-handed bundles are lowest in energy where the ions are located at the serines. PMID- 24239549 TI - Construction and characterization of functional anti-epiregulin humanized monoclonal antibodies. AB - Growth factors are implicated in several processes essential for cancer progression. Specifically, epidermal growth factor (EGF) family members, including epiregulin (EREG), are important prognostic factors in many epithelial cancers, and treatments targeting these molecules have recently become available. Here, we constructed and expressed humanized anti-EREG antibodies by variable domain resurfacing based on the three-dimensional (3D) structure of the Fv fragment. However, the initial humanized antibody (HM0) had significantly decreased antigen-binding affinity. Molecular modeling results suggested that framework region (FR) residues latently important to antigen binding included residue 49 of the light chain variable region (VL). Back mutation of the VL49 residue (tyrosine to histidine) generated the humanized version HM1, which completely restored the binding affinity of its murine counterpart. Importantly, only one mutation in the framework may be necessary to recover the binding capability of a humanized antibody. Our data support that HM1 exerts potent antibody-dependent cellular cytotoxicity (ADCC). Hence, this antibody may have potential for further development as a candidate therapeutic agent and research tool. PMID- 24239550 TI - Icilin inhibits E2F1-mediated cell cycle regulatory programs in prostate cancer. AB - Aberrant expression of cell cycle regulators have been implicated in prostate cancer development and progression. Therefore, understanding transcriptional networks controlling the cell cycle remain a challenge in the development of prostate cancer treatment. In this study, we found that icilin, a super-cooling agent, down-regulated the expression of cell cycle signature genes and caused G1 arrest in PC-3 prostate cancer cells. With reverse-engineering and an unbiased interrogation of a prostate cancer-specific regulatory network, master regulator analysis discovered that icilin affected cell cycle-related transcriptional modules and identified E2F1 transcription factor as a target master regulator of icilin. Experimental analyses confirmed that icilin reduced the activity and expression levels of E2F1. These results demonstrated that icilin inactivates a small regulatory module controlling the cell cycle in prostate cancer cells. Our study might provide insight into the development of cell cycle-targeted cancer therapeutics. PMID- 24239551 TI - Expression analysis of ATAD3 isoforms in rodent and human cell lines and tissues. AB - ATAD3 (ATPase family AAA-Domain containing protein 3) is a mitochondrial inner membrane ATPase with unknown but vital functions. Initial researches have focused essentially on the major p66-ATAD3 isoform, but other proteins and mRNAs are described in the data banks. Using a set of anti-peptide antibodies and by the use of rodent and human cell lines and organs, we tried to detail ATAD3 gene expression profiles and to verify the existence of the various ATAD3 isoforms. In rodent, the single ATAD3 gene is expressed as a major isoform of 67 kDa, (ATAD3l; long), in all cells and organs studied. A second isoform, p57-ATAD3s (small), is expressed specifically throughout brain development and in adult, and overexpressed around the peri-natal period. p57-ATAD3s is also expressed in neuronal and glial rodent cell lines, and during in vitro differentiation of primary cultured rat oligodendrocytes. Other smaller isoforms were also detected in a tissue-specific manner. In human and primates, ATAD3 paralogues are encoded by three genes (ATAD3A, 3B and 3C), each of them presenting several putative variants. Analyzing the expression of ATAD3A and ATAD3B with four specific anti peptide antibodies, and comparing their expressions with in vitro expressed ATAD3 cDNAs, we were able to observe and define five isoforms. In particular, the previously described p72-ATAD3B is confirmed to be in certain cases a phosphorylated form of ATAD3As. Moreover, we observed that the ATAD3As phosphorylation level is regulated by insulin and serum. Finally, exploring ATAD3 mRNA expression, we confirmed the existence of an alternative splicing in rodent and of several mRNA isoforms in human. Considering these observations, we propose the development of a uniform denomination for ATAD3 isoforms in rodent and human. PMID- 24239552 TI - Identification of H ferritin-dependent and independent genes in K562 differentiating cells by targeted gene silencing and expression profiling. AB - Ferritin is best known as the key molecule in intracellular iron storage, and is involved in several metabolic processes such as cell proliferation, differentiation and neoplastic transformation. We have recently demonstrated that the shRNA silencing of the ferritin heavy subunit (FHC) in a melanoma cell line is accompanied by a consistent modification of gene expression pattern leading to a reduced potential in terms of proliferation, invasiveness, and adhesion ability of the silenced cells. In this study we sought to define the repertoire of genes whose expression might be affected by FHC during the hemin-induced differentiation of the erythromyeloid cell line K562. To this aim, gene expression profiling was performed in four different sets of cells: i) wild type K562; ii) sh-RNA FHC-silenced K562; iii) hemin-treated wild-type K562; and iv) hemin-treated FHC-silenced K562. Statistical analysis of the gene expression data, performed by two-factor ANOVA, identified three distinct classes of transcripts: a) Class 1, including 657 mRNAs whose expression is modified exclusively during hemin-induced differentiation of K562 cells, independently from the FHC relative amounts; b) Class 2, containing a set of 70 mRNAs which are consistently modified by hemin and FHC-silencing; and c) Class 3, including 128 transcripts modified by FHC-silencing but not by hemin. Our data indicate that FHC may function as a modulator of gene expression during erythroid differentiation and add new findings to the knowledge of the complex gene network modulated during erythroid differentiation. PMID- 24239553 TI - Identification and expression pattern of two novel alternative splicing variants of EEF1D gene of dairy cattle. AB - Our recent genome-wide association study (GWAS) has identified 105 genome-wide significant SNPs for milk production traits. Of these, one SNP (rs109661298) for milk fat percentage is located within the first intron of the bovine EEF1D gene on BTA14, thus that the EEF1D gene was considered as a novel candidate in dairy cattle. Until now, however, its genomic organization remains undetermined yet and no studies of EEF1D in relation to milk production traits have been reported. To layout the groundwork for the validation of gene function in dairy cattle, we herein investigated its expression pattern in lactating dairy cows. With rapid amplification of 5' cDNA end (5' RACE), two novel alternatively spliced transcript variants of 1202bp and 2195bp were isolated in bovine mammary in lactation, named EEF1Da and EEF1Db (GenBank: KC190039 and KC190038KC190039KC190038). Such two variants contain the different first exon from each other (exon1a vs exon1b: 294bp vs 1287bp) with no overlap and the same remaining 7 exons. Coding sequence similarity between EEF1Da and EEF1Db and three of human EEF1D transcript variants were 85-88%. With semi-quantitative and quantitative real-time RT-PCR, we found that the mRNA level of EEF1Da was similar to the overall EEF1D mRNA and much higher than EEF1Db in the mammary of lactating cows, indicating EEF1Da functions as the dominant transcript variant to encode the EEF1D protein. Tissue expression pattern showed that the mRNA expression of EEF1D and EEF1Da in mammary gland was significantly higher compared with other 7 tissues (P<0.05, P<0.01) with the exception of EEF1D between mammary and lung. Together, our findings present the first report on the alternative splicing of the bovine EEF1D gene and provided basis for further investigation on function validation of EEF1D in dairy cattle. PMID- 24239554 TI - Interaction of thioflavin T with amyloid fibrils of apolipoprotein A-I N-terminal fragment: resonance energy transfer study. AB - Apolipoprotein A-I is amenable to a number of specific mutations associated with hereditary systemic amyloidoses. Amyloidogenic properties of apoA-I are determined mainly by its N-terminal fragment. In the present study Forster resonance energy transfer between tryptophan as a donor and Thioflavin T as an acceptor was employed to obtain structural information on the amyloid fibrils formed by apoA-I variant 1-83/G26R/W@8. Analysis of the dye-fibril binding data provided evidence for the presence of two types of ThT binding sites with similar stoichiometries (bound dye to monomeric protein molar ratio ~10), but different association constants (~6 and 0.1MUM(-1)) and ThT quantum yields in fibril associated state (0.08 and 0.05, respectively). A beta-strand-loop-beta-strand structural model of 1-83/G26R/W@8 apoA-I fibrils has been proposed, with potential ThT binding sites located in the solvent-exposed grooves of the N terminal beta-sheet layer. Reasoning from the expanded FRET analysis allowing for heterogeneity of ThT binding centers and fibril polymorphism, the most probable locations of high- and low-affinity ThT binding sites were attributed to the grooves T16_Y18 and D20_L22, respectively. PMID- 24239555 TI - Cloning and expression of melatonin receptors in the mudskipper Boleophthalmus pectinirostris: their role in synchronizing its semilunar spawning rhythm. AB - The mudskipper Boleophthalmus pectinirostris, a burrow-dwelling fish inhabiting intertidal mudflats, spawns only once during the spawning season around either the first or last lunar quarters. To understand the molecular mechanisms regulating this semilunar spawning rhythm, we cloned all melatonin receptor subtypes (mtnr1a1.4, mtnr1a1.7, mtnr1b, and mtnr1c). Expression of three melatonin receptor subtypes (except mtnr1c) was found in the ovaries. In contrast, the expression of all receptor subtypes was found in the diencephalon and the pituitary. In the fully-grown follicles, only mtnr1a1.7 mRNA was detected in both the isolated follicle layers and denuded oocytes. Interestingly, the transcript levels of both mtnr1a1.4 in the diencephalon and mtnr1a1.7 in the ovary displayed two cycles within one lunar month, and peaked around the first and last lunar quarters. We used 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), a maturation-inducing hormone, as a biomarker to examine the involvement of melatonin receptors in the control of the spawning cycle. Melatonin significantly increased the plasma DHP level 1h post intraperitoneal injection. Melatonin also directly stimulated ovarian fragments in vitro to produce a significantly higher amount of DHP. Taken together, these results provided the first evidence that melatonin receptors were involved in the synchronization of the semilunar spawning rhythm in the female mudskipper by acting through the HPG axis and/or directly on ovarian tissues to stimulate the production of DHP. PMID- 24239556 TI - Growth hormone and retinal ganglion cell function: QNR/D cells as an experimental model. AB - Retinal ganglion cells (RGCs) have been shown to be sites of growth hormone (GH) production and GH action in the embryonic (embryo day 7, ED7) chick neural retina. Primary RGC cell cultures were previously used to determine autocrine or paracrine actions of GH in the retina, but the antibody used in their immunopanning (anti-Thy-1) is no longer available. We have therefore characterized an immortalized neural retina (QNR/D) cell line derived from ED7 embryonic quail as a replacement experimental model. These cells express the GH gene and have GH receptor (GHR)-immunoreactivity. They are also immunoreactive for RGC markers (islet-1, calretinin, RA4) and neural fibers (neurofilament, GAP 43, vimentin) and they express the genes for Thy-1, neurotrophin 3 (NTF3), neuritin 1 (NRN1) and brn3 (POU4F). These cells are also electrically active and therefore resemble the RGCs in the neural retina. They are also similarly responsive to exogenous GH, which induces overexpression of the neurotrophin 3 and insulin-like growth factor (IGF) 1 genes and stimulates cell survival, as in the chick embryo neural retina. QNR/D cells are therefore a useful experimental model to assess the actions of GH in retinal function. PMID- 24239557 TI - Molecular cloning and multifunctional characterization of GRIM-19 (gene associated with retinoid-interferon-induced mortality 19) homologue from turbot (Scophthalmus maximus). AB - GRIM-19 (gene associated with retinoid-interferon-induced mortality 19), a novel cell death regulatory gene, plays important roles in cell apoptosis, embryogenesis, mitochondrial respiratory chain and immune response. To date, little information is known about fish GRIM-19 characteristics except orange spotted grouper (Epinephelus coioides). Here a new GRIM-19 gene is identified and characterized from turbot (Scophthalmus maximus), an economic marine fish in China and Europe. Briefly, turbot GRIM-19 is a 595-bp gene encoding a 144 amino acids protein, which shares the closest relationship with Atlantic halibut (Hippoglossus hippoglossus). The expression of turbot grim-19 in liver, spleen and kidney is up-regulated by the infection of Vibrio anguillarum and LCDV (lymphocystis disease virus). Subsequently, a recombinant protein of turbot GRIM 19 is acquired and the anti-bacterial function is proved by liquid culture inhibition experiment. The subcellular location indicates that turbot GRIM-19 is co-localized with STAT3 in the cytoplasm, which is mainly determined by GRIM-19 41-84 amino acids and STAT3 1-321 amino acids. Finally, the involvements of turbot GRIM-19 in cell apoptosis and NF-kappaB pathway are investigated. All these data help to understand GRIM-19 function in fish, as well as provide the application possibility of GRIM-19 in fish disease resistance breeding. PMID- 24239558 TI - A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes. AB - Type 2 diabetes (T2D) is a disease that is characterized by raised levels of glucose in the blood combined with insulin resistance and relative insulin deficiency. The pathogenesis of type 2 diabetes is associated with the induction of the unfolded protein response (UPR). While UPR aims to restore tissue homeostasis following stress of the endoplasmic reticulum (ER), prolonged ER stress triggers apoptosis at least in part through the unfolded protein response (UPR)-activated transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP). CHOP has elevated as a critical mediator connecting accumulation and aggregation of unfolded proteins in the ER and oxidative stress and also contributes to the induction of apoptosis in beta-cell (beta-cell) - cells under conditions of increased insulin demand. p21 is a cell cycle regulator that is implicated in the regulation of the UPR by various mechanisms involving inhibition of apoptosis and facilitation of the regeneration capacity of the beta cells. In this review we summarize the role of ER stress in the pathogenesis of type 2 diabetes which is associated with the induction of the unfolded protein response (UPR). We also review recent evidence associating p21 activity with beta cell health and regenerative capacity by mechanisms that may interfere with the effects of p21 in the UPR or operate independently of ER stress. Most likely understanding the molecular details of the pathogenesis of type 2 diabetes will be beneficial for the management of the disease. PMID- 24239559 TI - Biochemical characterization of thioredoxin reductase from Babesia bovis. AB - This paper addresses the identification, cloning, expression, purification and functional characterization of thioredoxin reductase from Babesia bovis, the etiological agent of babesiosis. The work deals with in vitro steady state kinetic studies and other complementary analyses of the thioredoxin reductase found in the pathogenic protist. Thioredoxin reductase from B. bovis was characterized as a homodimeric flavoprotein that catalyzes the NADPH-dependent reduction of Trx with a high catalytic efficiency. Moreover, the enzyme exhibited a disulfide reductase activity using DTNB as substrate, being this activity highly sensitive to inhibition by Eosin B. The thioredoxin reductase/thioredoxin system can reduce oxidized glutathione and S-nitrosoglutathione. Our in vitro data suggest that antioxidant defense in B. bovis could be supported by this enzyme. We have performed an enzymatic characterization, searching for targets for rational design of inhibitors. This work contributes to the better understanding of the redox biochemistry occurring in the parasite. PMID- 24239560 TI - The role of cannabinoid 1 receptor expressing interneurons in behavior. AB - Schizophrenia is a devastating neurodevelopmental disorder that affects approximately 1% of the population. Reduced expression of the 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of the disease and is encoded by the GAD1 gene. In schizophrenia, GAD67 downregulation occurs in multiple interneuronal subpopulations, including the cannabinoid receptor type 1 positive (CNR1+) cells, but the functional consequences of these disturbances are not well understood. To investigate the role of the CNR1-positive GABA-ergic interneurons in behavioral and molecular processes, we employed a novel, miRNA mediated transgenic mouse approach. We silenced the Gad1 transcript using a miRNA engineered to specifically target Gad1 mRNA under the control of Cnr1 bacterial artificial chromosome. Behavioral characterization of our transgenic mice showed elevated and persistent conditioned fear associated with an auditory cue and a significantly altered response to an amphetamine challenge. These deficits could not be attributed to sensory deficits or changes in baseline learning and memory. Furthermore, HPLC analyses revealed that Cnr1/Gad1 mice have enhanced serotonin levels, but not dopamine levels in response to amphetamine. Our findings demonstrate that dysfunction of a small subset of interneurons can have a profound effect on behavior and that the GABA-ergic, monoamine, and cannabinoid systems are functionally interconnected. The results also suggest that understanding the function of various interneuronal subclasses might be essential to develop knowledge-based treatment strategies for various mental disorders including schizophrenia and substance abuse. PMID- 24239561 TI - Age and race effects on pain sensitivity and modulation among middle-aged and older adults. AB - This study tested the effects of aging and race on responses to noxious stimuli using a wide range of stimulus modalities. The participants were 53 non-Hispanic blacks and 138 non-Hispanic white adults, ages 45 to 76 years. The participants completed a single 3-hour sensory testing session where responses to thermal, mechanical, and cold stimuli were assessed. The results suggest that there are selected age differences, with the older group less sensitive to warm and painful heat stimuli than middle-aged participants, particularly at the knee. This site effect supports the hypothesis that the greatest decrement in pain sensitivity associated with aging occurs in the lower extremities. In addition, there were several instances where age and race effects were compounded, resulting in greater race differences in pain sensitivity among the older participants. Overall, the data suggest that previously reported race differences in pain sensitivity emerged in our older samples, and this study contributes new findings in that these differences may increase with age in non-Hispanic blacks for temporal summation and both heat and cold immersion tolerance. We have added to the aging and pain literature by reporting several small to moderate differences in responses to heat stimuli between middle- and older-age adults. PERSPECTIVE: This study found that the greatest decline in pain sensitivity with aging occurs in the lower extremities. In addition, race differences in pain sensitivity observed in younger adults were also found in our older sample. PMID- 24239562 TI - Peripheral oxytocin treatment affects the rat adreno-medullary catecholamine content modulating expression of vesicular monoamine transporter 2. AB - The neuropeptide oxytocin has been shown to influence on neuroendocrine function. The aim of the present study was to investigate the effect of peripheral oxytocin treatment on the synthesis, uptake and content of adreno-medullary catecholamine. For this purpose oxytocin (3.6MUg/100g body weight, s.c) was administrated to male rats once a day over 14 days. In order to assess the effect of peripheral oxytocin treatment on adreno-medullary catecholamine we measured epinephrine and norepinephrine content and gene expression of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. Our results show a significant increase of epinephrine (1.7 fold, p<0.05) and norepinephrine (1.5-fold, p<0.05) content in oxytocin treated animals compared to saline treated ones. Oxytocin treatment had no effect either on mRNA or protein level of TH and NET. Under oxytocin treatment the increase in VMAT2 mRNA level was not statistically significant, but it caused a significant increase in protein level of VMAT2 (3.7-fold, p<0.001). These findings indicate that oxytocin treatment increases catecholamine content in the rat adrenal medulla modulating VMAT2 expression. PMID- 24239563 TI - Low-dose aspirin use after diagnosis of colorectal cancer does not increase survival: a case-control analysis of a population-based cohort. AB - BACKGROUND & AIMS: Individuals who began taking low-dose aspirin before they were diagnosed with colorectal cancer were reported to have longer survival times than patients who did not take this drug. We investigated survival times of patients who begin taking low-dose aspirin after a diagnosis of colorectal cancer in a large population-based cohort study. METHODS: We performed a nested case-control analysis using a cohort of 4794 patients diagnosed with colorectal cancer from 1998 through 2007, identified from the UK Clinical Practice Research Datalink and confirmed by cancer registries. There were 1559 colorectal cancer-specific deaths, recorded by the Office of National Statistics; these were each matched with up to 5 risk-set controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), based on practitioner-recorded aspirin usage. RESULTS: Overall, low-dose aspirin use after a diagnosis of colorectal cancer was not associated with colorectal cancer specific mortality (adjusted OR = 1.06; 95% CI: 0.92-1.24) or all-cause mortality (adjusted OR = 1.06; 95% CI: 0.94-1.19). A dose-response association was not apparent; for example, low-dose aspirin use for more than 1 year after diagnosis was not associated with colorectal cancer-specific mortality (adjusted OR = 0.98; 95% CI: 0.82-1.19). There was also no association between low-dose aspirin usage and colon cancer-specific mortality (adjusted OR = 1.02; 95% CI: 0.83-1.25) or rectal cancer-specific mortality (adjusted OR = 1.10; 95% CI: 0.88-1.38). CONCLUSIONS: In a large population-based cohort, low-dose aspirin usage after diagnosis of colorectal cancer did not increase survival time. PMID- 24239564 TI - Analysis of the resilience of team performance during a nuclear emergency response exercise. AB - The current work presents results from a cognitive task analysis (CTA) of a nuclear disaster simulation. Audio-visual records were collected from an emergency room team composed of individuals from 26 different agencies as they responded to multiple scenarios in a simulated nuclear disaster. This simulation was part of a national emergency response training activity for a nuclear power plant located in a developing country. The objectives of this paper are to describe sources of resilience and brittleness in these activities, identify cues of potential improvements for future emergency simulations, and leveraging the resilience of the emergency response system in case of a real disaster. Multiple CTA techniques were used to gain a better understanding of the cognitive dimensions of the activity and to identify team coordination and crisis management patterns that emerged from the simulation exercises. PMID- 24239565 TI - Improvement of hand function using different surfaces and identification of difficult movement post stroke in the Box and Block Test. AB - This study determined the impact of changing block surfaces on hand function, as well as identified particularly time-consuming movement components post stroke, measured by the Box and Block Test (BBT). Eight chronic stroke survivors and eight age- and gender-matched control subjects participated in this study. The BBT score (number of blocks moved) and time for seven movement components were compared for three different block surfaces (wood, paper, and rubber). The rubber blocks improved BBT scores 8% (compared to all other conditions) not only for control subjects but also for the paretic and non-paretic hands of stroke survivors, by reducing movement time for finger closing and contact-to-lift. Modifying daily objects' surfaces with rubber could help stroke survivors' hand function. The paretic hand displayed notably slower movement for contact-to-lift, transport-release, reach before barrier, and reach after barrier suggesting that therapies may focus on goal directed reaching and object grasping/releasing. PMID- 24239566 TI - Assessment of a simple obstacle detection device for the visually impaired. AB - A simple obstacle detection device, based upon an automobile parking sensor, was assessed as a mobility aid for the visually impaired. A questionnaire survey for mobility needs was performed at the start of this study. After the detector was developed, five blindfolded sighted and 15 visually impaired participants were invited to conduct travel experiments under three test conditions: (1) using a white cane only, (2) using the obstacle detector only and (3) using both devices. A post-experiment interview regarding the usefulness of the obstacle detector for the visually impaired participants was performed. The results showed that the obstacle detector could augment mobility performance with the white cane. The obstacle detection device should be used in conjunction with the white cane to achieve the best mobility speed and body protection. PMID- 24239567 TI - Identity crisis of Th17 cells: many forms, many functions, many questions. AB - Th17 cells are a subset of CD4(+) effector T cells characterized by expression of the IL-17-family cytokines, IL-17A and IL-17F. Since their discovery nearly a decade ago, Th17 cells have been implicated in the regulation of dozens of immune mediated inflammatory diseases and cancer. However, attempts to clarify the development and function of Th17 cells in human health and disease have generated as many questions as answers. On one hand, cytokine expression in Th17 cells appears to be remarkably dynamic and is subject to extensive regulation (both positive and negative) in tissue microenvironments. On the other hand, accumulating evidence suggests that the human Th17 subset is a heterogeneous population composed of several distinct pro- and anti-inflammatory subsets. Clearly, Th17 cells as originally conceived no longer neatly fit the long standing paradigm of stable and irrepressible effector T cell function. Here we review current concepts surrounding human Th17 cells, with an emphasis on their plasticity, heterogeneity, and their many, tissue-specific functions. In spite of the challenges ahead, a comprehensive understanding of Th17 cells and their relationship to human disease is key to ongoing efforts to develop safer and more selective anti-inflammatory medicines. PMID- 24239568 TI - Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. AB - Inflammation is associated with the development of diseases characterized by altered nutrient metabolism. Although an acute inflammatory response is host protective and normally self-limited, chronic low-grade inflammation associated with metabolic diseases is sustained and detrimental. The resolution of inflammation involves the termination of neutrophil recruitment, counterregulation of proinflammatory mediators, stimulation of macrophage mediated clearance, and tissue remodeling. Specialized proresolving lipid mediators (SPMs)-resolvins, protectins, and maresins-are novel autacoids that resolve inflammation, protect organs, and stimulate tissue regeneration. Here, we review evidence that the failure of resolution programs contributes to metabolic diseases and that SPMs may play pivotal roles in their resolution. PMID- 24239570 TI - Solid-phase plate-reader quantification of specific PCR products by measurement of band-specific ethidium bromide fluorescence. AB - Real-time PCR is widely employed to quantify PCR products across a range of applications. However, accurate real-time PCR is not always technically feasible, and alternative methods for PCR product quantification can be expensive and time consuming to validate. We have developed an inexpensive, rapid, and immediately accessible protocol to quantify PCR products, by measuring ethidium bromide fluorescence of PCR products excised from agarose gels. This protocol has relevance to a broad range of methods in molecular biology where quantification of PCR products is necessary. PMID- 24239571 TI - Rapid and selective enzymatic assay for L-methionine based on a pyrophosphate detection system. AB - An enzymatic assay for L-methionine was developed by coupling adenosylmethionine synthetase (AdoMetS) to a pyrophosphate (PP(i)) detection system, which was constructed using pyruvate, phosphate dikinase. To expand the use of this assay, the PP(i) detection system was embodied as three different forms, which allowed PP(i) to be measured by UV, visible, and fluorescent light detectors. The assay system was robust and could tolerate the addition of inorganic phosphate and ATP to the assay mixtures. L-Methionine could be accurately determined by coupling the PP(i) detection system and AdoMetS. This AdoMetS coupling assay was highly selective to L-methionine and exhibited no significant activity to other proteinaceous amino acids, ammonia, or urea, unlike conventional enzymatic assays for L-methionine. Spike and recovery tests showed that the AdoMetS assay could accurately and reproducibly determine increases in L-methionine in human plasma samples without any pretreatment to remove proteins and potentially interfering low-molecular-weight molecules. The high selectivity and robustness of the AdoMetS assay provide rapid and high-throughput analysis of L-methionine in various kinds of analytes. PMID- 24239572 TI - Spectrophotometric activity microassay for pure and recombinant cytochrome P450 type nitric oxide reductase. AB - Nitric oxide reductase (NOR) of the P450 oxidoreductase family accepts electrons directly from its cofactor, NADH, to reduce two nitric oxide (NO) molecules to one nitrous oxide molecule and water. The enzyme plays a key role in the removal of radical NO produced during respiratory metabolism, and applications in bioremediation and biocatalysis have been identified. However, a rapid, accurate, and sensitive enzyme assay has not yet been developed for this enzyme family. In this study, we optimized reaction conditions for the development of a spectrophotometric NOR activity microassay using NOC-5 for the provision of NO in solution. We also demonstrate that the assay is suitable for the quantification and characterization of P450-type NOR. The K(m) and k(cat) kinetic constants obtained by this assay were comparable to the values determined by gas chromatography, but with improved convenience and cost efficiency, effectively by miniaturization. To our knowledge, this is the first study to present the quantification of NOR activity in a kinetic microassay format. PMID- 24239573 TI - Chiral separation-based ligand exchange by open-tubular capillary electrochromatography. AB - Chiral ligand-exchange enantioseparation of aliphatic and aromatic amino acids was successfully performed using a new open-tubular zwitterionic column with tentacle-type polymer stationary phase. The polymeric stationary phase was prepared using 3-chloro-2-hydroxypropyl methacrylate (HPMA-Cl), a new reactive monomer. The preparation procedure of the open-tubular column included silanization, in situ graft polymerization with HPMA-Cl, and L-histidine (L-His) modification. L-His was used as a chiral ligand-exchange selector and copper(II) as a central ion. Successful enantioseparation of six pairs of amino acid enantiomers was achieved with a buffer of 5 mM CuSO4, 20 mM (NH4)2SO4 at pH 3.0. PMID- 24239569 TI - Weighing in on adipocyte precursors. AB - Obesity, defined as an excessive increase in white adipose tissue (WAT), is a global health epidemic. In obesity, WAT expands by increased adipocyte size (hypertrophy) and number (hyperplasia). The location and cellular mechanisms of WAT expansion greatly affect the pathogenesis of obesity. However, the cellular and molecular mechanisms regulating adipocyte size, number, and depot-dependent expansion in vivo remain largely unknown. This perspective summarizes previous work addressing adipocyte number in development and obesity and discusses recent advances in the methodologies, genetic tools, and characterization of in vivo adipocyte precursor cells allowing for directed study of hyperplastic WAT growth in vivo. PMID- 24239574 TI - Synthesis of haptens and development of an indirect enzyme-linked immunosorbent assay for tris(2,3-dibromopropyl) isocyanurate. AB - A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed for detection of tris(2,3-dibromopropyl) isocyanurate (TBC). Polyclonal antibodies against TBC were raised from synthesized haptens and then screened against various coating antigens. After optimization of the immunoassay conditions, the linear range and IC50 value of the assay were 0.30-100 and 5.17 MUg/L, respectively, with little cross-reactivity (<=2%). Recovery of various samples (water, serum, soil) was tested and the values ranged from 68% to 110%. This ciELISA was also applied to determine TBC in the riverside soil of the Liuyang River, and the results were compared with the data obtained by UHPLC MS/MS. The experimental assay results confirmed that this proposed immunoassay is a specific, sensitive, and reliable method for determination and monitoring of TBC. PMID- 24239575 TI - A chromogenic substrate for solid-phase detection of phospholipase A2. AB - A method for solid-phase detection of phospholipase A2 (PLA2) was developed. The method uses 1-octanoyloxynaphthalene-3-sulfonic acid, which was found to be a good substrate of PLA2. The substrate is hydrolyzed by PLA2 into 1-naphthol-3 sulfonic acid, which is spontaneously coupled with coexisting diazonium salt to form a red-purple azo dye. Streptomyces and bovine pancreatic PLA2 spotted on a nitrocellulose membrane could be detected by this method with considerable sensitivity. In addition, colonies of recombinant Escherichia coli producing bacterial PLA2 were distinguishable from those producing an inactive mutant PLA2, facilitating high-throughput screening in directed evolution of the enzyme. PMID- 24239576 TI - Ethylene-induced changes in lignification and cell wall-degrading enzymes in the roots of mungbean (Vigna radiata) sprouts. AB - As an important regulator, ethylene inhibits root growth and development in plants. To determine the mechanism of ethylene on root elongation growth and lateral root formation, ethylene-induced lignification and cell wall-degrading enzymes in the roots of mungbean sprouts were tested. We initially observed that primary root elongation and lateral root numbers were inhibited, while lignin content was enhanced by ethephon (ETH). Cell wall remolding proteins, polygalacturonase (PG) and carboxymethyl cellulose (Cx) activities were reduced, but alpha-expansins and xyloglucan endotransglucosylases/hydrolases (XTH) were enhanced by ETH. The promotion in lignin production was correlated with changes in activities of key lignin biosynthesis enzymes and hydrogen peroxide (H2O2) content. These actions induced by ETH were altered via treatment with an ethylene perception antagonist (Ag+). We subsequently demonstrated that the role of endogenous ethylene in regulating root elongation growth and lateral root formation were correlated with lignification and cell wall-degrading enzymes, respectively. These results suggested that the ethylene-regulated inhibition of primary root elongation growth was caused by an increase in lignification that reinforced the cell wall and shortened root length, and the suppression of lateral root formation was linked to activities of PG, Cx, alpha-expansins and XTH. PMID- 24239577 TI - Radon levels in groundwaters and natural radioactivity in soils of the volcanic region of La Garrotxa, Spain. AB - Groundwater radon level and soil radionuclide concentration have been measured in the volcanic region of La Garrotxa (Catalonia, Spain) to further research on the origin and dynamics of high radon levels over volcanic materials found in this region. Water samples from different aquifers have been collected from wells and springs and the water radon levels obtained have been lower than 30 Bq l(-1). Soil samples have been collected from different geological formations (volcanic and non-volcanic), being Quaternary sedimentary deposits those that have presented the highest mean values of (40)K, (226)Ra and (232)Th concentrations (448 +/- 70 Bq kg(-1), 35 +/- 5 Bq kg(-1) and 38 +/- 5 Bq kg(-1), respectively). Additionally, indoor/outdoor terrestrial radiation absorbed dose rate in air have been measured to better characterize the region from the radiological point of view. Terrestrial radiation absorbed dose rates measurement points have been chosen on the basis of geological and demographical considerations and the results obtained, from 27 to 91 nGy h(-1), show a clear relation with geological formation materials. The highest terrestrial gamma absorbed dose rate is observed over Quaternary sedimentary deposits as well. All these results help to better understand previous surveys related with indoor and outdoor radon levels and to reinforce the hypotheses of a radon transport through the fissure network. PMID- 24239578 TI - Intermolecular interactions between cucurbit[7]uril and pilocarpine. AB - The interactions between cucurbit[7]uril (CB7) macrocycles and pilocarpine (PIL) were investigated in aqueous solution by using (1)H NMR and circular dichroism (CD) spectroscopic techniques. The characterizations of the freeze-drying solid complex were conducted by electrospray ionization mass spectroscopy (ESI-MS), Fourier transform-infrared spectroscopy (FT-IR), thermogravimetry, and differential scanning calorimetry (DSC) techniques. The DSC and thermogravimetry confirmed the production of a thermally stable solid complex. The NMR, CD and ESI MS measurements confirmed asymmetric induction during the complexation reaction, in which the gamma-lactone ring of PIL (not the imidazole nucleus) has been fully encapsulated within the cavity of CB7. The stability of the drug has significantly enhanced as evidenced by the high-performance liquid chromatographic (HPLC) method. The results are discussed in the context of utilizing non-conventional supramolecular host-guest approaches to enhance the chemical stability in aqueous media of hydrophilic PIL drugs as model compounds. The non-classical stereospecific interactions between CB7 and PIL drugs are also highlighted. PMID- 24239579 TI - The influence of lipid composition and surface charge on biodistribution of intact liposomes releasing from hydrogel-embedded vesicles. AB - Mixed drug delivery systems possess advantages over discrete systems, and can be used as a strategy to design more effective formulations. They are more valuable if the embedded particles perform well, rather than using drugs that have been affected by the surrounding vehicle. In order to address this concept, different liposomes have been incorporated into hydrogel to evaluate the potential effect on the controlled release of liposomes. Radiolabeled liposomes, with respect to different acyl chain lengths (DMPC, DPPC, or DSPC) and charges (neutral, negative [DSPG], or positive [DOTAP]) were integrated into chitosan-glycerophosphate. The results obtained from the biodistribution showed that the DSPC liposomes had the highest area under the curve (AUC) values, both in the blood (206.5%ID/gh(-1)) and peritoneum (622.3%ID/gh(-1)), when compared to the DPPC and DMPC formulations, whether in liposomal hydrogel or dispersion. Interesting results were observed in that the hydrogel could reverse the peritoneal retention of negatively charged liposomes, increasing to 8 times its AUC value, to attain the highest amount among all formulations. The interactions between the liposomes and chitosan-glycerophosphate, confirmed by the Fourier transform infrared (FTIR) spectra as shifted characteristic peaks, were observed in the combined systems. Overall, the hydrogel could control the release of intact liposomes, which could be manipulated by both the liposome type and interactions between the two vehicles. PMID- 24239580 TI - Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. AB - Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. PMID- 24239581 TI - Formation of mannitol hemihydrate in freeze-dried protein formulations--a design of experiment approach. AB - Since the discovery of mannitol hemihydrate, this form of mannitol has been seen as potentially negative with regard to the stability of pharmaceutical formulations. The formation of mannitol hemihydrate is reported in several case studies; however, no systematic investigation has been performed so far. In this study, design of experiments was applied for response surface modelling of mannitol hemihydrate formation. The formulation parameters investigated in a composite face-centred design were the overall solid content, protein concentration, protein type and the ratio between mannitol and sucrose. Additionally, annealing as process parameter was included in a full factorial mixed design. For two proteins, models with a high goodness of fit (R(2): 0.82 and 0.93) and goodness of prediction (Q(2): 0.78 and 0.89) were achieved. Inclusion of the process parameter annealing resulted in models of similar quality. The successful application of design of experiments showed that the most prominent factors enhancing the formation of hemihydrate were a high protein concentration, low relative mannitol content and annealing at -20 degrees C. PMID- 24239582 TI - SpALF4: a newly identified anti-lipopolysaccharide factor from the mud crab Scylla paramamosain with broad spectrum antimicrobial activity. AB - Anti-lipopolysaccharide factors (ALFs) are antimicrobial peptides with binding and neutralizing activities to lipopolysaccharide (LPS) in crustaceans. This study identified and characterized a novel ALF homolog (SpALF4) from the mud crab Scylla paramamosain. The complete cDNA of SpALF4 had 756 bp with a 381 bp open reading frame encoding a protein with 126 aa. The deduced protein contained a signal peptide and a LPS-binding domain. SpALF4 shared the highest identity with PtALF5 at amino acid level but exhibited low similarity with most of other crustacean ALFs. Furthermore, different from the previously identified three SpALF homologs and most of other ALFs, SpALF4 had a low isoelectric point (pI) for the mature peptide and the LPS-binding domain with the values of 6.93 and 6.74, respectively. These results indicate that SpALF4 may be a unique ALF homolog with special biological function in the mud crab. Similar to the spatial structure of ALFPm3, SpALF4 contains three alpha-helices packed against a four strand beta-sheet, and an amphipathic loop formed by a disulphide bond between two conserved cysteine residues in LPS-binding domain. SpALF4, mainly distributed in hemocytes, could be upregulated by Vibrio harveyi, Staphylococcus aureus, or white spot syndrome virus. Recombinant SpALF4 could inhibit the growth of Gram negative bacteria (V. harveyi, Vibrio anguillarum, Vibrio alginolyticus, Aeromonas hydrophila, Pseudomonas putida), Gram-positive bacteria (S. aureus and Bacillus megaterium), and a fungus Candida albicans to varying degrees. Further study showed that it could also bind to all the aforementioned microorganisms except S. aureus. These results demonstrate that SpALF4 is a unique ALF homolog with potent antimicrobial activity against bacteria and fungi. This characteristic suggests SpALF4 plays an essential function in immune defense against pathogen invasion in mud crab. PMID- 24239583 TI - A simple immunofixation test for induced C3 degradation in disease states (including C3 nephritic factor) and its correlation with kidney biopsy. AB - Complement dysregulation from an uncontrolled activation of the alternate pathway can be mediated by C3 Nephritic Factor and results in C3 glomerulopathy. Identification of C3 degradation products C3c and C3d in patient serum provides evidence of uncontrolled complement activation. It is possible to detect C3c and C3d in patient serum by an immunofixation assay which induces in vitro C3 degradation. The clinical performance of the immunofixation assay has been assessed by comparing the assay results with findings from immunostaining of kidney biopsies. The immunofixation assay is a simple and reliable technique for detection of C3 degradation on a widely available platform and can be used to provide corroborative evidence of acquired complement dysregulation in patients with C3 glomerulopathy. PMID- 24239584 TI - Is testis variation the key to understanding why males seem so different from one another? Commentary on "Examining sources of variation in HPG axis function among individuals and populations of the dark-eyed juncos". By Christine M. Bergeon Burns, Kimberly A. Rosvall Thomas P. Hahn, Gregory E. Demas and Ellen D. Ketterson. PMID- 24239585 TI - Is highly challenging and progressive balance training feasible in older adults with Parkinson's disease? AB - OBJECTIVE: To develop a highly challenging and progressive group balance training regime specific to Parkinson's disease (PD) symptoms and to investigate its feasibility in older adults with mild to moderate PD. DESIGN: Intervention study, before-after trial with a development and feasibility design. SETTING: University hospital setting. PARTICIPANTS: Feasibility was evaluated in older adults (N=5; mean age, 72y; age range, 69-80y) with mild to moderate idiopathic PD. INTERVENTION: A balance training regime emphasizing specific and highly challenging exercises, performed 3 times per week for 12 weeks, was developed through discussion and workshops by a group of researchers and physiotherapists. MAIN OUTCOME MEASURES: Indicators of feasibility included attendance rate, safety (adverse events, physical function, and pain), participants' perceptions of the intervention (level of difficulty of the exercises, motivation level, and appreciation), and efficacy of the intervention (balance performance assessed with the Mini-Balance Evaluation Systems Test [Mini-BESTest]). RESULTS: The incidence rate was high (93%) for attendance and low (1.2%) for adverse events. Ratings by the participants indicated progression throughout the training period. All participants considered the training motivational and stated that they would recommend it to others. The efficacy of the intervention measured with the Mini BESTest showed that 4 out of 5 participants improved their balance performance. CONCLUSIONS: These findings support the overall feasibility of this novel balance program in older adults with mild to moderate PD. However, to further evaluate the efficacy of the program, a larger randomized controlled trial is required. PMID- 24239586 TI - Difficulty in disengaging attention from threatening facial expressions in anxiety: a new approach in terms of benefits. AB - BACKGROUND AND OBJECTIVES: Recent work suggests that the ability to disengage attention from threatening information is impaired in anxiety. The present study compared the difficulty to disengage from angry, fearful and neutral faces in Low Trait Anxious individuals (LTA) versus High Trait Anxious individuals (HTA) at two stages of facial expression processing (i.e., initial and later face processing). METHODS: HTA and LTA individuals performed an attentional shifting task to assess attentional disengagement. Participants had to classify a peripheral target letter, appearing 200 or 500 ms after a face was displayed. RESULTS: LTA individuals were quicker when the letter appears after 500 ms compared to 200 ms regardless of the emotion of the face. An impaired disengagement in HTA individuals was observed for fearful and angry faces (i.e., no reaction differences between 200 and 500 ms) but not for neutral faces. These results suggest that it is particularly difficult for anxious individuals to switch attention from one stimulus to another if the engaged stimulus is a threatening face. LIMITATIONS: Generalisation of our results is restricted to trait anxiety and emotional facial expression processing. CONCLUSIONS: LTA individuals can benefit from the emotional processing (i.e., from 200 to 500 ms) to make a rapid attentional shift and engagement to the target stimuli whereas HTA individuals did not and continue to process the threatening facial expression. These results also point out the role of top down processes on the regulation of disengagement from threatening information in anxiety. PMID- 24239587 TI - Investigating cognitive flexibility as a potential mechanism of mindfulness in Generalized Anxiety Disorder. AB - BACKGROUND AND OBJECTIVES: Research suggests mindfulness-based treatments may enhance efficacy of CBT for Generalized Anxiety Disorder (GAD). One hypothesized mechanism of mindfulness is cognitive flexibility; however, research findings to date are mixed as to a) whether cognitive inflexibility represents a characteristic of GAD, and b) whether mindfulness impacts cognitive flexibility. It is proposed that limitations in study methodology may partially account for these mixed findings. The present study investigated cognitive flexibility as a potential mechanism of mindfulness in a sample with elevated GAD symptoms using a modified emotional Stroop switching task while attempting to control for limitations of previous research. The purpose of the study was: 1) to explore cognitive inflexibility as a potential characteristic of GAD, and 2) to examine whether a brief mindfulness induction has measurable impact on cognitive flexibility. METHODS: A total of 66 participants (53 with elevated GAD symptoms, and 13 non-anxious) were randomized to a mindful-breathing, music-assisted relaxation, or thought wandering condition prior to completing an emotional Stroop and emotional Stroop switching task. RESULTS: Results suggest that GAD may be characterized by an inflexible style of responding, and exposure to mindfulness and relaxation result in partial improvements in cognitive flexibility. LIMITATIONS: Limitations of this study include small sample size, brief induction period, and use of an analog sample. CONCLUSIONS: The present findings suggest that mindfulness may be associated with partial improvement in cognitive flexibility. PMID- 24239588 TI - Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda. AB - OBJECTIVES: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. METHODS: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. RESULTS: Milk inhibited p24 production by >=50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 +/- 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. CONCLUSIONS: Breast milk from HIV-infected women showed homotypic and cross subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers. PMID- 24239589 TI - The relationship between MEG and fMRI. AB - In recent years functional neuroimaging techniques such as fMRI, MEG, EEG and PET have provided researchers with a wealth of information on human brain function. However none of these modalities can measure directly either the neuro-electrical or neuro-chemical processes that mediate brain function. This means that metrics directly reflecting brain 'activity' must be inferred from other metrics (e.g. magnetic fields (MEG) or haemodynamics (fMRI)). To overcome this limitation, many studies seek to combine multiple complementary modalities and an excellent example of this is the combination of MEG (which has high temporal resolution) with fMRI (which has high spatial resolution). However, the full potential of multi-modal approaches can only be truly realised in cases where the relationship between metrics is known. In this paper, we explore the relationship between measurements made using fMRI and MEG. We describe the origins of the two signals as well as their relationship to electrophysiology. We review multiple studies that have attempted to characterise the spatial relationship between fMRI and MEG, and we also describe studies that exploit the rich information content of MEG to explore differing relationships between MEG and fMRI across neural oscillatory frequency bands. Monitoring the brain at "rest" has become of significant recent interest to the neuroimaging community and we review recent evidence comparing MEG and fMRI metrics of functional connectivity. A brief discussion of the use of magnetic resonance spectroscopy (MRS) to probe the relationship between MEG/fMRI and neurochemistry is also given. Finally, we highlight future areas of interest and offer some recommendations for the parallel use of fMRI and MEG. PMID- 24239590 TI - On the interpretation of weight vectors of linear models in multivariate neuroimaging. AB - The increase in spatiotemporal resolution of neuroimaging devices is accompanied by a trend towards more powerful multivariate analysis methods. Often it is desired to interpret the outcome of these methods with respect to the cognitive processes under study. Here we discuss which methods allow for such interpretations, and provide guidelines for choosing an appropriate analysis for a given experimental goal: For a surgeon who needs to decide where to remove brain tissue it is most important to determine the origin of cognitive functions and associated neural processes. In contrast, when communicating with paralyzed or comatose patients via brain-computer interfaces, it is most important to accurately extract the neural processes specific to a certain mental state. These equally important but complementary objectives require different analysis methods. Determining the origin of neural processes in time or space from the parameters of a data-driven model requires what we call a forward model of the data; such a model explains how the measured data was generated from the neural sources. Examples are general linear models (GLMs). Methods for the extraction of neural information from data can be considered as backward models, as they attempt to reverse the data generating process. Examples are multivariate classifiers. Here we demonstrate that the parameters of forward models are neurophysiologically interpretable in the sense that significant nonzero weights are only observed at channels the activity of which is related to the brain process under study. In contrast, the interpretation of backward model parameters can lead to wrong conclusions regarding the spatial or temporal origin of the neural signals of interest, since significant nonzero weights may also be observed at channels the activity of which is statistically independent of the brain process under study. As a remedy for the linear case, we propose a procedure for transforming backward models into forward models. This procedure enables the neurophysiological interpretation of the parameters of linear backward models. We hope that this work raises awareness for an often encountered problem and provides a theoretical basis for conducting better interpretable multivariate neuroimaging analyses. PMID- 24239591 TI - Air pollution effects on fetal and child development: a cohort comparison in China. AB - In Tongliang, China, a coal-fired power plant was the major pollution source until its shutdown in 2004. We enrolled two cohorts of nonsmoking women and their newborns before and after the shutdown to examine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and fetal and child growth and development. PAHs were used to measure exposure to air pollution generated by the power plant. Using PAH-DNA adduct levels as biomarkers for the biologically effective dose of PAH exposure, we examined whether PAH-DNA adduct levels were associated with birth outcome, growth rate, and neurodevelopment. Head circumference was greater in children of the second cohort, compared with the first (p = 0.001), consistent with significantly reduced levels of cord blood PAH-DNA adducts in cohort II (p < 0.001) and reduced levels of ambient PAHs (p = 0.01). PMID- 24239592 TI - Steroid exposure during larval development of Xenopus laevis affects mRNA expression of the reproductive pituitary-gonadal axis in a sex- and stage dependent manner. AB - Steroids are known to influence the reproductive pituitary-gonadal axis in adult amphibians. Here, we studied the effects of hormones on pituitary and gonadal mRNA expression during the development of Xenopus laevis. Tadpoles at NF 58 (prometamorphosis) and at NF 66 (freshly metamorphosed) were exposed for three days to 17beta-estradiol (E2), tamoxifen (TAM), testosterone (T), dihydrotestosterone (DHT) at 10(-7)M, and flutamide (FLU) at 10(-6)M. In both genders at NF 58 and 66, T and DHT decreased luteinizing hormone beta (lhbeta), but increased follicle stimulating hormone beta (fshbeta), while FLU induced lhbeta specifically in males. In the testis steroidogenic genes (p450 side chain cleavage enzyme, p450scc; steroid acute regulatory protein, star) at NF 58 showed a similar pattern as for lhbeta, while the response at NF 66 was only partially present. In females, TAM induced lhbeta at NF 58, while E2 decreased lhbeta and increased fshbeta at NF 66. In the ovaries, no alterations were observed for the steroidogenic genes. Summarizing, gonadotropic and steroidogenic mRNA expression may indicate control of androgen level during testis differentiation in male tadpoles at NF 58. In females the non-responsiveness of steroidogenic genes could be a sign of gonadal quiescence during pre-pubertal stages. PMID- 24239593 TI - Genetic dissection of the psychotomimetic effects of cannabinoid exposure. AB - Cannabis use is an established risk factor for the development of schizophrenia and related psychotic disorders. Factors that may mediate susceptibility to the psychosis-inducing effects of cannabis include the age at onset of first cannabis use, genetic predisposition, as well as interaction with other environmental risk variables. Clinical and preclinical genetic studies provide increasing evidence that, in particular, genes encoding proteins implicated in dopamine signalling are implicated in the cannabis-psychosis association. In the present review, we focus on both human and animal studies which have focused on identifying the neuronal basis of these interactions. We conclude that further studies are required to provide greater mechanistic insight into the long-term and neurodevelopmental effects of cannabis use, with implications for improved understanding of the cannabis-psychosis relationship. PMID- 24239595 TI - Emotion response coherence: a dual-process perspective. AB - Emotions are widely thought to involve coordinated responses across multiple responses (e.g., experiential, behavioral, and physiological). However, empirical support for this general "response coherence" postulate is inconsistent. The present research takes a dual-process perspective, suggesting that response coherence might be conditional upon response system (i.e., automatic versus reflective). In particular, we tested the hypothesis that response coherence should be maximal within each system and minimal across the two systems. To test this prediction, 36 participants underwent an anger provocation while two relatively automatic (anger accessibility and physiology) and two relatively reflective (anger experience and instrumental behavior) responses were measured. As predicted, coherence was found within the automatic and reflective systems, but not across them. Implications for emotion response coherence, dual-process frameworks, and the functions of emotions are discussed. PMID- 24239594 TI - Preliminary findings of the effects of rivastigmine, an acetylcholinesterase inhibitor, on working memory in cocaine-dependent volunteers. AB - Long-term cocaine use is a risk factor for the onset of neurocognitive impairment. This study sought to determine whether the cholinesterase inhibitor rivastigmine could improve neurocognitive performance in cocaine-dependent individuals. Cocaine-dependent individuals who were not seeking treatment at the time of enrollment in the study were randomly assigned to receive placebo (n=16), rivastigmine 3mg (n=13), or rivastigmine 6mg (n=12). The baseline neurocognitive assessment, which included measures of attention/information processing (as measured by the Continuous Performance Task-II (CPT-II)), verbal learning/episodic memory (as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)), and working memory (as measured by the Dual N-Back Task), was conducted prior to the administration of study medication (Day 0). The follow-up assessment was conducted on Day 8 after the participants had received rivastigmine or placebo for 7days (Day 2-8). Rivastigmine administration significantly improved performance on one measure of working memory span (mean n back span). This study provides additional data showing that cocaine-associated neurocognitive impairment, specifically working memory deficits, can be remediated, at least to some degree. PMID- 24239596 TI - Transcription analysis of two Eomesodermin genes in lymphocyte subsets of two teleost species. AB - Eomesodermin (Eomes), a T-box transcription factor, is a key molecule associated with function and differentiation of CD8(+) T cells and NK cells. Previously, two teleost Eomes genes (Eomes-a and -b), which are located on different chromosomes, were identified and shown to be expressed in zebrafish lymphocytes. For the present study, we identified these genes in rainbow trout and ginbuna crucian carp. Deduced Eomes-a and -b amino acid sequences in both fish species contain a highly conserved T-box DNA binding domain. In RT-PCR, both Eomes transcripts were readily detectable in a variety of tissues in rainbow trout and ginbuna. The high expression of Eomes-a and -b in brain and ovary suggests involvement in neurogenesis and oogenesis, respectively, while their expression in lymphoid tissues presumably is associated with immune functions. Investigation of separated lymphocyte populations from pronephros indicated that both Eomes-a and b transcripts were few or absent in IgM(+) lymphocytes, while relatively abundant in IgM(-)/CD8alpha(+) and IgM(-)/CD8alpha(-) populations. Moreover, we sorted trout CD8alpha(+) lymphocytes from mucosal and non-mucosal lymphoid tissues and compared the expression profiles of Eomes-a and -b with those of other T cell related transcription factor genes (GATA-3, T-bet and Runx3), a Th1 cytokine gene (IFN-gamma) and a Th2 cytokine gene (IL-4/13A). Interestingly, the tissue distribution of Eomes-a/b, T-bet, and Runx3 versus IFN-gamma transcripts did not reveal simple correlations, suggesting tissue-specific properties of CD8alpha(+) lymphocytes and/or multiple modes that drive IFN-gamma expressions. PMID- 24239597 TI - Characterization of the interleukin 1 receptor-associated kinase 4 (IRAK4) encoding gene in salmonid fish: the functional copy is rearranged in Oncorhynchus mykiss and that factor can impair TLR signaling in mammalian cells. AB - The interleukin 1 receptor-associated kinase 4 (IRAK4) is an essential factor for TLR-mediated activation of the host's immune functions subsequent to pathogen contact. We have characterized the respective cDNA and gene sequences from three salmonid species, salmon, rainbow trout and maraena whitefish. The gene from salmon is structured into eleven exons, as is the mammalian homologue, while exons have been fused in the genes from the two other salmonid species. Rainbow trout expresses also a pseudogene at low levels. Its basic structure resembles more closely the primordial gene than the functional copy does. The N-terminal death domain and the C-terminal protein kinase domain of the factors are better conserved throughout evolution than the linker domain. The deduced amino acid sequences of the factors from all three species group together in an evolutionary tree of IRAK4 factors. Scrutinizing expression and function of IRAK4 from rainbow trout, we found its highest expression in head kidney and spleen and lowest expression in muscle tissue. Infecting fish with Aeromonas salmonicida did not modulate its expression during 72 h of observation. Expression of a GFP-tagged trout IRAK4 revealed, expectedly, its cytoplasmic localization in human HEK-293 cells. However, this factor significantly quenched in a dose-dependent fashion not only the pathogen-induced stimulation of NF-kappaB factors in the HEK-293 reconstitution system of TLR2 signaling, but also the basal NF-kappaB levels in unstimulated control cells. Our data unexpectedly imply that IRAK4 is involved in establishing threshold levels of active NF-kappaB in resting cells. PMID- 24239598 TI - Characterization of cathepsin B gene from orange-spotted grouper, Epinephelus coioides involved in SGIV infection. AB - The lysosomal cysteine protease cathepsin B of papain family is a key regulator and signaling molecule that involves in various biological processes, such as the regulation of apoptosis and activation of virus. In the present study, cathepsin B gene (Ec-CB) was cloned and characterized from orange-spotted grouper, Epinephelus coioides. The full-length Ec-CB cDNA was composed of 1918 bp and encoded a polypeptide of 330 amino acids with higher identities to cathepsin B of teleosts and mammalians. Ec-CB possessed typical cathepsin B structural features including an N-terminal signal peptide, the propeptide region and the cysteine protease domain which were conserved in other cathepsin B sequences. Phylogenetic analysis revealed that Ec-CB was most closely related to Lutjanus argentimaculatus. RT-PCR analysis showed that Ec-CB transcript was expressed in all the examined tissues which abundant in spleen, kidney and gill. After challenged with Singapore grouper iridovirus (SGIV) stimulation, the mRNA expression of cathepsin B in E. coioides was up-regulated at 24 h post-infection. Subcellular localization analysis revealed that Ec-CB was distributed predominantly in the cytoplasm. When the fish cells (GS or FHM) were treated with the cathepsin B specific inhibitor CA-074Me, the occurrence of CPE induced by SGIV was delayed, and the viral gene transcription was significantly inhibited. Additionally, SGIV-induced typical apoptosis was also inhibited by CA-074Me in FHM cells. Taken together, our results demonstrated that the Ec-CB might play a functional role in SGIV infection. PMID- 24239599 TI - Assessment of a sequential phase extraction procedure for uranium-series isotope analysis of soils and sediments. AB - The study of uranium-series (U-series) isotopes in soil and sediment materials has been proposed to quantify rates and timescales of soil production and sediment transport. Previous works have studied bulk soil or sediment material, which is a complex assemblage of primary and secondary minerals and organic compounds. However, the approach relies on the fractionation between U-series isotopes in primary minerals since they were liberated from the parent rock via weathering. In addition, secondary minerals and organic compounds have their own isotopic compositions such that the composition of the bulk material may not reflect that of primary minerals. Hence, there is a need for a sample preparation procedure that allows the isolation of primary minerals in soil or fluvial sediment samples. In this study, a sequential extraction procedure to separate primary minerals from soils and sediments was assessed. The procedure was applied to standard rock sample powders (TML-3 and BCR-2) to test whether it introduced any artefactual radioactive disequilibrium. A new step was introduced to remove the clay-sized fraction (<2 um). Significant amounts (5-14%) of U and Th were removed from the rock standards during the procedure. No significant alteration in ((234)U/(238)U) and ((230)Th/(238)U) activity ratios of the rock standards occurred during the procedure. Aliquots of soil sample were subjected to the sequential extraction process to test how each step modifies the uranium-series activity ratios and mineralogy. Although no secondary minerals were detected in the unleached soil aliquots, the sequential leaching process removed up to 17% of U and Th and modified their activity ratios by up to 3%. The modification of the activity ratios poses a demand for careful means to avoid redistribution of isotopes back to the residual phase during phase extraction. PMID- 24239600 TI - A traditional herbal formula, Hyangsa-Pyeongwi san (HPS), improves quality of life (QoL) of the patient with functional dyspepsia (FD): randomized double blinded controlled trial. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Hyangaa-Pyeongwi san is the most well known description in Traditional Chinese Medicine for treating functional gastrointestinal disorders. Functional dyspepsia (FD) is a main concern of intimidating quality of life (QoL) in recent days. Although many medicines have been developed to improve FD symptoms as well as QoL, there are no potential drugs and treatments for FD. The aim of this study is to investigate the effects of Hyangaa-Pyeongwi san (HPS) on QoL of patients with FD. METHODS: This study was designed as a randomized, double blinded, placebo controlled, and parallel group trial. Participants received either placebo or HPS (9.68g of HPS at once, three times daily) for 4-weeks, and the efficacy evaluations were performed by assessing the Nepean Dyspepsia Index (NDI) and functional dyspepsia-quality of life (FD-QoL) at 0-, 4- and 8-weeks. RESULTS: Total of 170 patients participated and were randomly allocated into placebo or HPS groups. Total symptom score of NDI decreased after 4-weeks trial in both groups (p>0.05). HPS significantly improved QoL scores, especially in the area of 'interference and eat/drink' in NDI (p=0.0031) as well as 'liveliness status', 'role-functioning status', and total score in FD-QoL (p=0.026 for liveliness status and p=0.035 for role functioning status). This significant improvement of FD-QoL had lasted for 4 weeks. CONCLUSION: HPS treatment is markedly effective in improving QoL in patients with FD. Moreover, we observed that this improvement had lasted for 4 weeks after finishing the trial through the follow-up study. PMID- 24239601 TI - Investigation into the mechanism of Eucommia ulmoides Oliv. based on a systems pharmacology approach. AB - ETHNOPHARMACOLOGY RELEVANCE: Though Traditional Chinese Medicine (TCM) has long been playing a significant role in the maintenance of health for people in Asia as well as many other places, the mechanism of its action still remains ambiguous for most of the plants used in TCM, such as Eucommia ulmoides Oliv., a kind of herb that is widely used to help regulate hypertension and the immune system nowadays. However, its functioning mechanism is still unknown. Thus it is necessary to exploit the mechanism of Eucommia ulmoides Oliv. METHODS: A systems pharmacology approach combining drug-likeness evaluation, oral bioavailability prediction, multiple drug targets prediction as well as network pharmacology techniques has been used. RESULTS: This comprehensive systematic approach helps successfully to identify 41 candidate compounds contained in Eucommia ulmoides Oliv. while 39 potential targets hit by these ingredients and helps to uncover the synergistic mechanism of action on a systematic level. CONCLUSIONS: Our work successfully explains the mechanism of the efficiency of Eucommia ulmoides Oliv. for the treatment of hypertension and enhancing immune. These results not only provide a new insight for the understanding of the chemical and pharmacological basis of Eucommia ulmoides Oliv., but also provide an efficient way for drug discovery from herbal medicine. PMID- 24239602 TI - Single-target RNA interference for the blockade of multiple interacting proinflammatory and profibrotic pathways in cardiac fibroblasts. AB - Therapeutic targets of broad relevance are likely located in pathogenic pathways common to disorders of various etiologies. Screening for targets of this type revealed CCN genes to be consistently upregulated in multiple cardiomyopathies. We developed RNA interference (RNAi) to silence CCN2 and found this single-target approach to block multiple proinflammatory and profibrotic pathways in activated primary cardiac fibroblasts (PCFBs). The RNAi-strategy was developed in murine PCFBs and then investigated in "individual" human PCFBs grown from human endomyocardial biopsies (EMBs). Screening of short hairpin RNA (shRNA) sequences for high silencing efficacy and specificity yielded RNAi adenovectors silencing CCN2 in murine or human PCFBs, respectively. Comparison of RNAi with CCN2 modulating microRNA (miR) vectors expressing miR-30c or miR-133b showed higher efficacy of RNAi. In murine PCFBs, CCN2 silencing resulted in strongly reduced expression of stretch-induced chemokines (Ccl2, Ccl7, Ccl8), matrix metalloproteinases (MMP2, MMP9), extracellular matrix (Col3a1), and a cell-to cell contact protein (Cx43), suggesting multiple signal pathways to be linked to CCN2. Immune cell chemotaxis towards CCN2-depleted PCFBs was significantly reduced. We demonstrate here that this RNAi strategy is technically applicable to "individual" human PCFBs, too, but that these display individually strikingly different responses to CCN2 depletion. Either genomically encoded factors or stable epigenetic modification may explain different responses between individual PCFBs. The new RNAi approach addresses a key regulator protein induced in cardiomyopathies. Investigation of this and other molecular therapies in individual human PCBFs may help to dissect differential pathogenic processes between otherwise similar disease entities and individuals. PMID- 24239604 TI - Synthesis of modified Trichinella spiralis disaccharide epitopes and a comparison of their recognition by chemical mapping and saturation transfer difference NMR. AB - A rat monoclonal antibody 9D4 raised against the cell surface N-glycan of the parasite Trichinella spirallis protects rats against further infection. The terminal disaccharide beta-d-Tyvp(1->3)beta-d-GalNAcp (2) represents the immunodominant portion of the antigenic determinant. Chemical mapping of the antibody binding site by functional group modification employing monodeoxy and mono-O-methyl congeners identified key polar contacts and topography of the bound disaccharide. We report here a comparison of the chemical mapping studies with the antigen topography inferred from saturation transfer difference (STD) NMR experiments. During chemical mapping several congeners of compound 2 showed substantially enhanced binding. Pairing of these functional group modifications to create derivatives 6 and 7 did not show additive free energy gains and STD NMR data point to small variations in mode of binding as a probable cause. Improved syntheses of disaccharides 2-7 are reported. PMID- 24239603 TI - Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes. AB - Pulmonary veins (PVs) are believed to be a crucial origin of atrial fibrillation. We recently reported that rat PV cardiomyocytes exhibit arrhythmogenic automaticity in response to norepinephrine. Herein, we further characterized the electrophysiological properties underlying the potential arrhythmogenicity of PV cardiomyocytes. Patch clamping studies revealed a time dependent hyperpolarization-activated inward current in rat PV cardiomyocytes, but not in left atrial (LA) myocytes. The current was Cs(+) resistant, and was not affected by removal of external Na(+) or K(+). The current was inhibited with Cd(2+), and the reversal potential was sensitive to changes in [Cl(-)] on either side of the membrane in a manner consistent with a Cl(-) selective channel. Cl(-) channel blockers attenuated the current, and slowed or completely inhibited the norepinephrine-induced automaticity. The biophysical properties of the hyperpolarization-activated Cl(-) current in rat PVs were different from those of ClC-2 currents previously reported: (i) the voltage-dependent activation of the Cl(-) current in rat PVs was shifted to negative potentials as [Cl(-)]i increased, (ii) the Cl(-) current was enhanced by extracellular acidification, and (iii) extracellular hyper-osmotic stress increased the current, whereas hypo osmotic cell swelling suppressed the current. qPCR analysis revealed negligible ClC-2 mRNA expression in the rat PV. These findings suggest that rat PV cardiomyocytes possess a peculiar voltage-dependent Cl(-) channel, and that the channel may play a functional role in norepinephrine-induced automaticity. PMID- 24239605 TI - Influence of antioxidant structure on local molecular mobility in amorphous sucrose. AB - The effect of the antioxidants gallic acid and methyl, propyl, and octyl gallate on the molecular mobility and hydrogen bond network in amorphous sucrose was studied. Solid amorphous sucrose films with and without the addition of antioxidants at a mole ratio of 1:5 (antioxidant/sucrose) were cast from solution onto quartz slides. Local molecular mobility from 0 to 70 degrees C was measured using tryptophan amino acid as a luminescent probe dispersed in the films. Phosphorescence from the tryptophan probe provides spectroscopic characteristics emission spectrum and lifetime-that are sensitive to changes in molecular mobility induced by the addition of antioxidants. Local molecular mobility detected by tryptophan increased in the following order: sucrosesucrose-gallic acid>sucrose-propyl gallate>sucrose>sucrose-octyl gallate) that was nearly the reverse of that seen in matrix mobility. Analysis of the differential effects of the antioxidants suggests that the presence of the hydroxyl benzoyl head group increased matrix molecular mobility and hydrogen bond strength while the saturated carbon chain decreased mobility and bond strength. The influence of the carboxyl group on matrix properties was comparable to that of the formyloxy group. These results indicate that the addition of specific functional ingredients such as antioxidants may significantly affect the physical properties and consequently functional properties of amorphous edible films in ways that might condition their use. The observed changes are closely related to the chemical structure of the added species. PMID- 24239606 TI - Efficient one-pot synthesis of tigogenin saponins and their antitumor activities. AB - An efficient synthesis of naturally occurring tigogenin triglycoside 1a and its three derivatives 1b-d bearing different carbohydrate moieties, as well as their antitumor activities, is described. Partially protected thiogalactosides bearing unprotected 2,4-OH or 4-OH groups were used to facilitate regioselective reactions for one-pot sequential multi-step glycosylation, which has significantly simplified the target molecule synthesis. The synthetic saponins 1a d exhibited much higher anti-tumor activities than the positive control cisplatin against the human epithelial cervical cancer cell (HeLa) as evaluated by CCK-8 assay. PMID- 24239607 TI - DCIR interacts with ligands from both endogenous and pathogenic origin. AB - C-type lectins on dendritic cells function as antigen uptake and signaling receptors, thereby influencing cellular immune responses. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is one of the best-studied C-type lectin receptors expressed on DCs and its glycan specificity and functional requirements for ligand binding have been intensively investigated. The carbohydrate specificity of dendritic cell immunoreceptor (DCIR), another DC-expressed lectin, was still debated, but we have recently confirmed DCIR as mannose/fucose-binding lectin. Since DC-SIGN and DCIR may potentially share ligands, we set out to elucidate the interaction of DCIR with established DC-SIGN-binding ligands, by comparing the carbohydrate specificity of DCIR and DC-SIGN in more detail. Our results clearly demonstrate that DC-SIGN has a broader glycan specificity compared to DCIR, which interacts only with mannotriose, sulfo-Lewis(a), Lewis(b) and Lewis(a). While most of the tested DC SIGN ligands bound DCIR as well, Candida albicans and some glycoproteins on some cancer cell lines were identified as DC-SIGN-specific ligands. Interestingly, DCIR strongly bound human immunodeficiency virus type 1 (HIV-1) gp140 glycoproteins, while its interaction with the well-studied DC-SIGN-binding HIV-1 ligand gp120 was much weaker. Furthermore, DCIR-specific ligands were detected on keratinocytes. Furthermore, the interaction of DCIR with its ligands was strongly influenced by the glycosylation of DCIR. In conclusion, we show that sulfo Lewis(a) is a high affinity ligand for DCIR and that DCIR interacts with ligands from both pathogenic and endogenous origin of which most are shared by DC-SIGN. PMID- 24239608 TI - Cardiomyocyte autophagy and cancer chemotherapy. AB - Autophagy, an evolutionally conserved process of controlled cellular cannibalization, plays a vital role in cardiac physiology. Perturbations in cardiomyocyte autophagy contribute to the pathogenesis of a wide range of cardiac diseases, many of which culminate in heart failure. With recent advances in cancer chemotherapy and consequent improvements in cancer survival, drug-induced toxicity to the heart has assumed greater importance. As a number of prominent cellular pathways are critical to the survival of both tumor cells and heart cells, it comes as little surprise that therapies targeting those pathways have consequences in both tissues. Little is known presently about cardiomyocyte autophagy, a prominent cellular response to stress, in the setting of chemotherapy, but preliminary evidence suggests an important and context dependent role. Dissecting the role of autophagy in "onco-cardiology" will likely yield insights into mechanisms underlying cardiomyopathy and may lead to novel means to protect the myocardium from chemotherapy-induced injury. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy". PMID- 24239610 TI - Numerical study of lipid translocation driven by nanoporation due to multiple high-intensity, ultrashort electrical pulses. AB - The dynamical translocation of lipids from one leaflet to another due to membrane permeabilization driven by nanosecond, high-intensity (>100kV/cm) electrical pulses has been probed. Our simulations show that lipid molecules can translocate by diffusion through water-filled nanopores which form following high voltage application. Our focus is on multiple pulsing, and such simulations are relevant to gauge the time duration over which nanopores might remain open, and facilitate continued lipid translocations and membrane transport. Our results are indicative of a N(1/2) scaling with pulse number for the pore radius. These results bode well for the use of pulse trains in biomedical applications, not only due to cumulative behaviors and in reducing electric intensities and pulsing hardware, but also due to the possibility of long-lived thermo-electric physics near the membrane, and the possibility for pore coalescence. PMID- 24239609 TI - Proteasomal and lysosomal protein degradation and heart disease. AB - In the cell, the proteasome and lysosomes represent the most important proteolytic machineries, responsible for the protein degradation in the ubiquitin proteasome system (UPS) and autophagy, respectively. Both the UPS and autophagy are essential to protein quality and quantity control. Alterations in cardiac proteasomal and lysosomal degradation are remarkably associated with most heart disease in humans and are implicated in the pathogenesis of congestive heart failure. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteasomal functional insufficiency or lysosomal insufficiency as a major pathogenic factor in the heart. This review article highlights some recent advances in the research into proteasome and lysosome protein degradation in relation to cardiac pathology and examines the emerging evidence for enhancing degradative capacities of the proteasome and/or lysosome as a new therapeutic strategy for heart disease. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy". PMID- 24239611 TI - Coupled gating modifies the regulation of cardiac ryanodine receptors by luminal Ca(2+). AB - Cardiac ryanodine receptors (RYR2s) infrequently exhibit coupled gating that is manifested by synchronous opening and closing. To better characterize this phenomenon, we investigated the regulation of coupled RYR2 channels by luminal Ca(2+) focusing on effects that are likely mediated by the true luminal activation mechanism. By reconstituting an ion channel into a planar lipid bilayer and using substantially lower concentration of luminal Ba(2+) (8mM, the virtual absence of Ca(2+)) and luminal Ca(2+) (8mM), we show that response of coupled RYR2 channels to caffeine at a diastolic cytosolic Ca(2+) (90nM) was affected by luminal Ca(2+) in a similar manner as for the single RYR2 channel except the gating behavior. Whereas, the single RYR2 channel responded to luminal Ca(2+) by prolongation in open and closed times, coupled RYR2 channels seemed to be resistant in this respect. In summary, we conclude that the class of Ca(2+) sites located on the luminal face of coupled RYR2 channels that is responsible for the channel potentiation by luminal Ca(2+) is functional and not structurally hindered by the channel coupling. Thus, the idea about non-functional luminal Ca(2+) sites as a source of the apparent gating resistance of coupled RYR2 channels to luminal Ca(2+) appears to be ruled out. PMID- 24239613 TI - Light shines through the spindrift--phylogeny of African torrent frogs (Amphibia, Anura, Petropedetidae). AB - Torrent frogs of the genus Petropedetes Reichenow, 1874 as currently understood have a disjunct distribution with species endemic to West, Central or East Africa. We herein present a phylogenetic analysis including all but one of the currently described 12 species of the genus. Maximum Likelihood and Bayesian analyses of combined nuclear (rag1, SIA, BDNF) and mitochondrial (16S, 12S, cytb) genes of more than 3500 base pairs, revealed clades corresponding to the three sub-Saharan regions. Molecular results are confirmed by morphological differences. Surprisingly, the three geographic clades do not form a monophyletic group with respect to closely related families Pyxicephalidae and Conrauidae and therefore require taxonomic changes. We resurrect Arthroleptides Nieden, 1911 for the East African taxa. The Central African taxa remain in the genus Petropedetes. The West African members are placed in the new genus Odontobatrachus gen. nov. The taxonomic position of the new genus remains incertae sedis as it was not assigned to any of the four families included in our analyses. Potential new species have been detected within all three major clades, pointing to a still not fully clarified diversity within African torrent frogs. PMID- 24239612 TI - The Ontology of Clinical Research (OCRe): an informatics foundation for the science of clinical research. AB - To date, the scientific process for generating, interpreting, and applying knowledge has received less informatics attention than operational processes for conducting clinical studies. The activities of these scientific processes - the science of clinical research - are centered on the study protocol, which is the abstract representation of the scientific design of a clinical study. The Ontology of Clinical Research (OCRe) is an OWL 2 model of the entities and relationships of study design protocols for the purpose of computationally supporting the design and analysis of human studies. OCRe's modeling is independent of any specific study design or clinical domain. It includes a study design typology and a specialized module called ERGO Annotation for capturing the meaning of eligibility criteria. In this paper, we describe the key informatics use cases of each phase of a study's scientific lifecycle, present OCRe and the principles behind its modeling, and describe applications of OCRe and associated technologies to a range of clinical research use cases. OCRe captures the central semantics that underlies the scientific processes of clinical research and can serve as an informatics foundation for supporting the entire range of knowledge activities that constitute the science of clinical research. PMID- 24239614 TI - Characterization of the response of in vitro cultured Myrtus communis L. plants to high concentrations of NaCl. AB - Effect of salt stress was examined in in vitro shoot cultures of Myrtus communis L. a species of the Mediterranean maquis. To determine the effects of high salt concentrations on myrtle plantlets and contribute toward understanding the mechanisms adopted from this species to counteract soil salinity, in vitro rooted shoots were transferred to a liquid culture medium containing 0, 125 or 250 mM NaCl for 30 days. After 15 and 30 days of in vitro culture, shoot and root growth, chlorosis and necrosis extension, chlorophylls, carotenoids, proline, arginine, cysteine and total sugars content, as well as guaiacol peroxidase (G POD, EC 1.11.1.7) and ascorbate peroxidase (APX, EC 1.11.1.11) activities were determined. In treated plants shoot and root growth, as well as chlorophyll content, significantly decreased, while carotenoids content was not affected by the NaCl treatment. Among osmolytes, proline did not significantly increase, arginine and cysteine decreased, while total sugars were found to be higher in the treated plants than in the control. Enhancement of G-POD and APX activities was positively related to increasing salt concentrations in the culture media, regardless of the exposure time. Salt-treated plants did not show significant changes in lipid peroxidation or DNA fragmentation after 30 days salt treatment, regardless of the NaCl concentrations applied. The results represent a contribution towards understanding the mechanisms adopted by this species to high salinity. PMID- 24239615 TI - Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes. AB - We examined whether glucocorticoids could modulate the expression of activation induced cytidine deaminase (AICDA), the principal regulator of the processes of immunoglobulin gene somatic hypermutation and class switch recombination in B lymphocytes. Treatment of human B cells with IL-4 and anti-CD40 antibody for 18 20h resulted in induction of expression of AICDA mRNA by over 10-fold. Dexamethasone at 10nM concentration inhibited AICDA induction by an average of 51.8% (p<0.0001). These effects of glucocorticoids were found to be dose dependent in the physiologic range and were reversible by co-treatment with a glucocorticoid receptor antagonist. Human B cell viability and proliferation were unaltered by glucocorticoid treatment. These data demonstrate that physiologic concentrations of glucocorticoids can act on human B lymphocytes through glucocorticoid receptor-mediated mechanisms to diminish the expression of AICDA, a key regulator of humoral immune responses. PMID- 24239617 TI - Chronic kidney disease. Preface. PMID- 24239616 TI - Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Delta(4)-tibolone. AB - Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3alpha-OH-tibolone and 3beta-OH-tibolone, and a delta-4 isomer (Delta(4)-TIB) that has both androgenic and progestagenic properties. Here, we show that 5alpha-dihydrotestosterone (DHT) and Delta(4)-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Delta(4)-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Delta(4)-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA. PMID- 24239618 TI - Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study. AB - Alteration in the HPA axis is a robust biomarker of anxiety and depression in adults, but questions remain about this association in pregnancy. We examined the longitudinal links between diurnal cortisol and mood symptoms from self-report questionnaire and diagnostic interview in an ethnically diverse, psychosocially at-risk sample of 101 women at mid-pregnancy and early third trimester. There were modest but significant associations between depression and elevated cortisol, indexed by a decreased morning level and diminished diurnal decline; the effects were strongest for diagnostic data from clinical interview. These effects were independent of socio-demographic factors and sleep disturbance. Associations with anxiety and trauma were generally non-significant. These findings extend prior work by showing that significant mood symptoms in pregnancy are associated with altered diurnal cortisol in pregnancy, which may have implications for maternal and child health. PMID- 24239619 TI - Spaced taste avoidance conditioning in Lymnaea. AB - We succeeded in taste avoidance conditioning with sucrose as the conditional stimulus (CS) and an electrical stimulus (~1000V, 80MUA) as the unconditional stimulus (US). With 15 paired CS-US presentations on a single day, we were able to elicit both short-term memory (STM) and long-term memory (LTM) persisting for at least one week. However, while STM was elicited with 5, 8, 10, and 20 paired presentations of the CS-US on a single day, LTM was not. We found, however, that if we inserted a 3h interval between a first and a second set of CS-US pairings that both 8 and 20 paired CS-US presentations on a single day was now sufficient to cause LTM formation. Exposing snails to bryostatin before or during training enhanced LTM formation such that 8 paired presentations of the CS-US resulted in LTM. PMID- 24239620 TI - Immunization with either prion protein fragment 95-123 or the fragment-specific antibodies rescue memory loss and neurodegenerative phenotype of neurons in olfactory bulbectomized mice. AB - Epidemiological studies demonstrated association between head injury (HI) and the subsequent development of Alzheimer's disease (AD). Certain hallmarks of AD, e.g. amyloid-beta (Abeta) containing deposits, may be found in patients following traumatic BI (TBI). Recent studies uncover the cellular prion protein, PrP(C), as a receptor for soluble polymeric forms of Abeta (sAbeta) which are an intermediate of such deposits. We aimed to test the hypothesis that targeting of PrP(C) can prevent Abeta related spatial memory deficits in olfactory bulbectomized (OBX) mice utilized here to resemble some clinical features of AD, such as increased level of Abeta, memory loss and deficit of the CNS cholin- and serotonin-ergic systems. We demonstrated that immunization with the a.a. 95-123 fragment of cellular prion (PrP-I) recovered cortical and hippocampus neurons from OBX induced degeneration, rescued spatial memory loss in Morris water maze test and significantly decrease the Abeta level in brain tissue of these animals. Affinity purified anti-PrP-I antibodies rescued pre-synaptic biomarker synaptophysin eliciting similar effect on memory of OBX mice, and protected hippocampal neurones from Abeta25-35-induced toxicity in vitro. Immunization OBX mice with a.a. 200-213 fragment of cellular prion (PrP-II) did not reach a significance in memory protection albeit having similar to PrP-I immunization impact on Abeta level in brain tissue. The observed positive effect of targeting the PrP-I by either active or passive immunization on memory of OBX mice revealed the involvement of the PrP(C) in AD-like pathology induced by olfactory bulbectomy. This OBX model may be a useful tool for mechanistic and preclinical therapeutic investigations into the association between PrP(C) and AD. PMID- 24239621 TI - Spatiotemporal integration of tactile patterns along and across fingers. AB - The volar sides of the fingers can be seen as the haptic counterpart to the fovea for visual perception. This study assessed the localisation of individual tactile stimuli and spatiotemporal patterns presented to the volar side of the fingers. Participants performed the localisation task by pointing at the perceived positions with a 3D tracker. Based on the pointing data, perceptual maps were devised in which perceived positions, their relationship to each other and to veridical stimulus positions could be analysed. Participants were able to accurately and consistently report the locations of the stimuli. Localisation of stimuli presented within a spatiotemporal pattern generally differed from localization of individual stimuli presented to the same positions. In most cases, stimuli were perceived as being spatially closer when they were presented within a spatiotemporal pattern compared to when being presented individually. Spatiotemporal integration along the fingers followed the predictions of the sensory saltation paradigm: The shorter the temporal delay between the two stimuli, the closer together they were perceived. For spatiotemporal patterns across fingers, the results were inconclusive: No general relationship between temporal delay and the difference between the perceived positions could be demonstrated, presumably because the effect could only be elicited in some finger combinations. Temporal delay did have, however, an effect on overall lateral shifts in localisation. PMID- 24239622 TI - Synthesis, biological evaluation and docking studies of 4-aryloxymethyl coumarins derived from substructures and degradation products of vancomycin. AB - Two series of 4-aryloxymethyl coumarins derived from the reaction of 4 bromomethyl coumarins with ethyl gallate and ethyl ester of N-Benzoyl tyrosine have been synthesized. Gallate ethers 3a-3g and tyrosine derivatives 4e-4j were most effective against Entercoccus faecalis. They were also found to be effective against Aspergillus niger and Candida albicans. Comparative docking studies with novobiocin have indicated better binding ability and higher 'C' score values than novobiocin. PMID- 24239624 TI - Synthesis and biological evaluation of 18F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging. AB - In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation. PMID- 24239623 TI - Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. AB - The benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-one core was discovered as a novel ERK5 (also known as MAPK7 and BMK1) inhibitor scaffold, previously. Further structure-activity relationship studies of this scaffold led to the discovery of ERK5-IN-1 (26) as the most selective and potent ERK5 inhibitor reported to date. 26 potently inhibits ERK5 biochemically with an IC50 of 0.162 +/- 0.006 MUM and in cells with a cellular EC50 for inhibiting epidermal growth factor induced ERK5 autophosphorylation of 0.09 +/- 0.03 MUM. Furthermore, 26 displays excellent selectivity over other kinases with a KINOMEscan selectivity score (S10) of 0.007, and exhibits exceptional bioavailability (F%) of 90% in mice. 26 will serve as a valuable tool compound to investigate the ERK5 signaling pathway and as a starting point for developing an ERK5 directed therapeutic agent. PMID- 24239625 TI - Unraveling phosphodiesterase surfaces. Identification of phosphodiesterase 7 allosteric modulation cavities. AB - The last findings of our group by using chemical genetic approaches have shown that PDE7 is an interesting target in neurodegenerative diseases. The following step in this travel to unravel PDE7 is the design of more selective inhibitors. In this sense we have proposed to perform an analysis of PDE7 surface to identify possible allosteric sites following by a docking study of different PDE7 inhibitors synthesized by our group. Thanks to these studies we have proved the existence of allosteric sites in PDE7 and we have been able to explain the binding modes of the employed PDE7 inhibitors. PMID- 24239626 TI - New aminopyrimidine derivatives as inhibitors of the TAM family. AB - In this study, we describe the synthesis of new pyrimidine analogs of BMS-777607, a potent and selective inhibitor of Met kinase. Inhibition of Met and Axl remained high whereas inhibition of Tyro3 and Mer decreased to some extend. The preferential moderate inhibition of the non-phosphorylated form of Abl1 of some derivatives suggests that they behave as type II inhibitors. This hypothesis was confirmed by docking studies into the structure of Met (3F82) and in a Tyro3 model where key interactions with the hinge region, the DFG-out motif and the allosteric pocket explain this inhibition. PMID- 24239627 TI - Meprin-beta regulates production of pro-inflammatory factors via a disintegrin and metalloproteinase-10 (ADAM-10) dependent pathway in macrophages. AB - Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as atherosclerosis. Meprin, an astacin metalloproteinase, has exhibited proinflammatory effects in vivo and in vitro studies. Here, we tried to further investigate the proinflammatory potential of meprin-beta and the possible underlying mechanisms in primary human peripheral blood macrophages. In our current study, ELISA assay revealed that meprin-beta increased the production of pro-inflammatory cytokines, including interleukin 1beta (IL-1beta), interleukin-18 and interleukin-6 (IL-6) in macrophages. However, meprin-beta shows no effects on the level of ligands of epidermal growth factor receptor (EGFR), and the activation of EGFR. The molecular mechanism was associated with activation of a disintegrin and metalloproteinase 10 (ADAM10) and the phosphorylation of IkappaB. Further analysis of upstream mechanisms showed that activation of NF-kappaB by meprin-beta was mediated by inhibiting ADAM10 downstream extracellular signal regulated kinase (ERK1/2) pathway. Taken together, these results indicated that meprin-beta exhibited pro-inflammatory effects by targeting activating ADAM10, leading to ERK1/2-mediated activation of NF-kappaB in macrophages, and this would make meprin-beta a strong candidate for further study as proinflammatory target. PMID- 24239628 TI - Retinoids and their biological effects against cancer. AB - There are more than 4000 natural and synthetic molecules structurally and/or functionally related to vitamin A. Retinoids are a class of these compounds that are structurally associated to vitamin A. The retinoids have a wide spectrum of functions. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation and apoptosis. It suppresses carcinogenesis in tumorigenic animal models for the skin, oral, lung, breast, bladder, ovarian and prostate. It is important how major retinoids may act in cancer treatment or prevention. The reports have indicated that lower levels of vitamin A in humans may be associated with relative type 1 cytokine dominance and a higher proportion of NK cells. In addition, very low vitamin A levels would be undesirable explaining the essential role of vitamin A in epithelial and general cell maturation and function. However, the cytokine shifts associated with moderately low levels of vitamin A may be in some ways beneficial in an environment where HIV infection, M. tuberculosis infection, or other type 1 infections are highly prevalent and/or when acquired immunity is cooperated. In this review, we intend to describe the biochemical and immunological functions of retinoids against cancer. PMID- 24239629 TI - Anti-hepatoma human single-chain Fv antibody and adriamycin conjugates with potent antitumor activity. AB - To construct an improved biological missile, an immunoconjugate ADM-Dex-ScFv-SA3 was synthesized, which was composed of a hepatocellular carcinoma-specific, single-chain Fv antibody (ScFv-SA3) and a highly potent cytotoxic drug, adriamycin (ADM), as the warhead. Oxidized Dextran T10 (Dex-T10) was used as a linker to connect these two moieties. The 40 KD soluble anti-hepatoma human Trx ScFv-SA3 protein was expressed in E. coli BL21 (DE3), using a prokaryotic expression vector, pET21a (+)-Trx-ScFv-SA3-His. It was purified using a His-Tag Ni-Agarose column and identified by western blot. The activity of Trx-ScFv-SA3 was verified by enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry to confirm that it specifically binds to the hepatocellular carcinoma cell line HepG2. To prepare ADM-Dex-ScFv-SA3, ADM was conjugated to the antibody at a molar ratio of 14.21:1. The antitumor effect of the conjugate was tested by MTT assay, plate colony formation assay and xenografts in a nude mice experimental model. In vitro experiments revealed that ADM-Dex-ScFv-SA3 could bind to tumor cells selectively and inhibit the proliferation and the colony formation ability of HepG2 cells. In vivo experiments showed that ADM-Dex-ScFv-SA3 suppressed the tumor growth and prolonged the median survival time in tumor-bearing mice. Tumor histology slides indicated a significantly slower tumor tissue proliferation in the ADM-Dex-ScFv-SA3 group. These data indicate that the targeted drug, ADM-Dex ScFv-SA3, may be a highly potent and selective therapy for the treatment of hepatoma. PMID- 24239630 TI - Design, preparation and application of nucleic acid delivery carriers. AB - Gene delivery vectors must deliver their cargoes into the cytosol or the nucleus, where DNA or siRNA functions in vivo. Therefore it is crucial for the rational design of the nucleic acid delivery carriers. Compared with viral vectors, non viral vectors have overcome some fatal defections in gene therapy. Whereas the most important issue for the non-viral vectors is the low transfection efficiency, which hinders the progress of non-viral carriers. Sparked by the structures of the virus and understanding of the process of virus infection, various biomimic structures of non-viral carriers were designed and prepared to improve the transfection issues in vitro and in vivo. However, less impressive results are achieved. In this review, we will investigate the evolution of the virus-mimicking carriers of nucleic acids for gene therapy, especially in cancer therapy; explore and discuss the relationship between the structures, materials and functions of the carriers, to provide guidance for establishing safe and highly efficient non-viral carriers for gene therapy. PMID- 24239631 TI - DPS - a rapid method for genome sequencing of DNA-containing bacteriophages directly from a single plaque. AB - Bacteriophages (phages) coexist with bacteria in all environments and influence microbial diversity, evolution and industrial production processes. As a result of this major impact of phages on microbes, tools that allow rapid characterization of phages are needed. Today, one of the most powerful methods for characterization of phages is determination of the whole genome using high throughput sequencing approaches. Here a direct plaque sequencing (DPS) is described, which is a rapid method that allows easy full genome sequencing of DNA containing phages using the Nextera XTTM kit. A combination of host-DNA removal followed by purification and concentration of the viral DNA, allowed the construction of Illumina-compatible sequencing libraries using the NexteraTM XT technology directly from single phage plaques without any whole genome amplification step. This method was tested on three Caudovirales phages; phi29 Podoviridae, P113g Siphoviridae and T4 Myovirdae, which are representative of >96% of all known phages, and were sequenced using the Illumina MiSeq platform. Successful de novo assembly of the viral genomes was possible. PMID- 24239632 TI - Evaluation of the performance of four methods for detection of hepatitis B surface antigen and their application for testing 116,455 specimens. AB - Hepatitis B surface antigen (HBsAg) is a crucial serum marker for the diagnosis of hepatitis B virus (HBV) infection. It is imperative to compare test results from different detection methods based on different principles. Four methods, chemiluminescent microparticle immunoassay (CMIA), electrochemiluminescent immunoassay (ECLIA), enzyme-linked immunosorbent assay (ELISA) and golden immunochromato-graphic assay (GICA) were applied to test the HBsAg level in 250 specimens. According to the EP12-A2 and EP15-A2 documents from Clinical and Laboratory Standards Institute (CLSI), the concentration at which repeated results are 50% positive (C50) of HBsAg detected by CMIA, ECLIA, ELISA and GICA was 0.05, 0.08, 0.15 and 15.0IU/ml, respectively. When the detection concentration of HBsAg was 0.5IU/ml, the imprecision degree of CMIA, ECLIA and ELISA was 8.1%, 5.9% and 14.9% respectively. When detecting high HBsAg level (>=20.0IU/ml) and HBsAg negative specimens, the consistency of the four methods was high, while for the low level (0.05-20.0IU/ml), the consistency was poor (except for the CMIA and ECLIA, P<0.05). When evaluation of the four methods in qualitative diagnosis of HBsAg level in the 116,455 specimens, there was no significant discrepancy among CMIA, CMIA and ECLIA, however, GICA was significantly different from the other 3 methods. Compared with CMIA, the false negative rate of ECLIA, ELISA and GICA was 0.2%, 1.3% and 12.3% respectively. In conclusion, GICA was only suitable for the preliminary screening of HBsAg positive individuals and ELISA can be applied to the qualitative diagnosis of HBsAg. Both CMIA and ECLIA were suitable for the quantitative determination of HBsAg. PMID- 24239633 TI - Efficient rescue of foot-and-mouth disease virus in cultured cells transfected with RNA extracted from clinical samples. AB - In this study, an RNA transfection was used to rescue infectious foot-and-mouth disease (FMD) virus from clinical samples in BHK-21 cell line for diagnosis of FMD. Tissue samples (n=190) were subjected to FMD virus isolation by conventional cell culture and also by RNA transfection. FMD virus was isolated from 62% of the clinical samples by RNA transfection, whereas virus was isolated only from 16% of the clinical samples in conventional cell culture method, suggesting better performance of the RNA transfection. Virus was rescued from 67% and 10% of ELISA negative but multiplex PCR positive samples by RNA transfection and conventional cell culture, respectively. The efficiency of transfection was studied on clinical samples subjected to temperature as high as 37 degrees C and varying pH (pH 4-9). Except up to 1 week of storage at 4 degrees C at pH 7.5, virus isolation was not possible by cell culture. Virus was rescued by transfection from samples stored at 4 degrees C for any of the applied pH up to 4 weeks, and when stored at 37 degrees C virus could be rescued up to 4 weeks at pH 7.5 suggesting the fitness of transfection to isolate virus from clinical samples stored under inappropriate conditions. The sequence data and antigenic relationships with the vaccine strains, between virus rescued by transfection and conventional cell culture, were comparable. The RNA transfection will help to increase the efficiency of virus isolation, diagnosis and molecular epidemiological studies. PMID- 24239634 TI - Production of adeno-associated virus (AAV) serotypes by transient transfection of HEK293 cell suspension cultures for gene delivery. AB - Adeno-associated virus (AAV) is being used successfully in gene therapy. Different serotypes of AAV target specific organs and tissues with high efficiency. There exists an increasing demand to manufacture various AAV serotypes in large quantities for pre-clinical and clinical trials. A generic and scalable method has been described in this study to efficiently produce AAV serotypes (AAV1-9) by transfection of a fully characterized cGMP HEK293SF cell line grown in suspension and serum-free medium. First, the production parameters were evaluated using AAV2 as a model serotype. Second, all nine AAV serotypes were produced successfully with yields of 10(13)Vg/L cell culture. Subsequently, AAV2 and AAV6 serotypes were produced in 3-L controlled bioreactors where productions yielded up to 10(13)Vg/L similar to the yields obtained in shake flasks. For example, for AAV2 10(13)Vg/L cell culture (6.8*10(11)IVP/L) were measured between 48 and 64h post transfection (hpt). During this period, the average cell specific AAV2 yields of 6800Vg per cell and 460IVP per cell were obtained with a Vg to IVP ratio of less than 20. Successful operations in bioreactors demonstrated the potential for scale-up and industrialization of this generic process for manufacturing AAV serotypes efficiently. PMID- 24239635 TI - Sometimes, it is OK to be coarse: quantifying ventricular fibrillation in the cardiac arrest victim. PMID- 24239637 TI - Ablation of right ventricular outflow tract tachycardia using a novel multipolar irrigated ablation catheter (nMARQ). PMID- 24239636 TI - Sudden cardiac death in children and adolescents between 1 and 19 years of age. AB - BACKGROUND: Understanding pediatric sudden cardiac death (SCD) may inform age specific prevention strategies. OBJECTIVE: To characterize potential underlying causes of SCD in children and adolescents METHODS: We performed a retrospective population-based study in Ontario, Canada, of all SCD cases in a 5-year period (2005-2009) involving persons aged 1-19 years identified from the comprehensive database of the Office of the Chief Coroner. Of 1204 coroner's cases, 351 potential SCD cases were reviewed. RESULTS: Of 116 cases of adjudicated SCD, there was no identifiable cause of death in 60 (52%). The majority were males (66%), and median age was 12.7 years. The incidence of SCD was greatest between 1 and 2 years (3.14 per 100,000 person-years), decreased, and then increased to 1.01 per 100,000 person-years (15-19 years). Autopsy findings were normal in 29 of 35 (83%) of children younger than 5 years and were more likely to be abnormal in those 10 years and older (odds ratio 9.0; 95% confidence interval 3.3-24.9). In 9%, the pathology findings may be of uncertain significance. Most events occurred in the home (68%). Activity level at the time of the event was associated with both age group (chi(2) = 34.9; P < .001) and autopsy findings (chi(2) = 28.9; P < .001). Events during moderate or vigorous activity were more common in those older than 10 years 16 of 66 (24%), and the majority had abnormal autopsy findings 13 of 18 (72%). DISCUSSION: Death in the very young is often caused by presumed primary arrhythmia syndromes, and death during exertion is typically seen in those with structural heart disease. CONCLUSION: These differences should inform age-specific diagnostic and prevention strategies. PMID- 24239638 TI - Essential roles of endogenous glucocorticoids and TNF/TNFR1 in promoting bone marrow eosinopoiesis in ovalbumin-sensitized, airway-challenged mice. AB - AIMS: Stress mechanisms paradoxically contribute to allergic episodes in humans and mice. Glucocorticoids (GC) and interleukin (IL)-5 synergically upregulate murine bone-marrow eosinophil production. Here we explored the role of endogenous GC in allergen-stimulated bone-marrow eosinophil production in ovalbumin sensitized/challenged mice. MAIN METHODS: In BALB/c or C57BL/6 mice, sensitized and intranasally challenged with ovalbumin, we monitored eosinophil numbers in freshly harvested or cultured bone-marrow, and plasma corticosterone levels. Metyrapone (MET) was used to inhibit GC synthesis, and RU486 to block GC actions. In sensitized mice challenged intraperitoneally, we examined the relationship between eosinophilia of bone-marrow and peritoneal cavity, in the absence or presence of RU486. In experiments involving in vivo neutralization of tumor necrosis factor-alpha (TNF) by specific antibodies, or using mice which lack functional type I TNF receptors (TNFRI), we evaluated the relationship between TNF blockade, corticosterone levels, RU486 or MET treatment and challenge-induced bone-marrow eosinophilia. KEY FINDINGS: RU486 or MET pretreatments abolished challenge-induced increases in eosinophil numbers in bone-marrow (in vivo and ex vivo), and in the peritoneal cavity. MET, but not RU486, prevented the challenge induced increase in corticosterone levels. Challenge-induced bone-marrow eosinophilia and corticosterone surge were abolished in TNFRI-deficient mice. Anti-TNF-treatment very effectively prevented challenge-induced bone-marrow eosinophilia, in the absence of RU486 or MET, but had no independent effect in the presence of either drug. SIGNIFICANCE: Endogenous GC was essential for allergen challenge-induced increases in eosinophil numbers inside bone-marrow. This effect required TNF and TNFRI, which suggests an immunoendocrine mechanism. PMID- 24239639 TI - Norepinephrine activates NF-kappaB transcription factor in cultured rat pineal gland. AB - AIMS: The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with beta1-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-kappaB (NF-kappaB) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-kappaB activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity. MAIN METHODS: Cultured rat pineal glands were incubated in the presence of two different NF-kappaB inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF kappaB activation in cultured rat pineal glands stimulated by NE. KEY FINDINGS: Our results showed that the p50/p50 homodimer of NF-kappaB is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity. SIGNIFICANCE: Here we present evidence that NF-kappaB is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-kappaB p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis. PMID- 24239640 TI - Involvement of MAPK signaling pathway in the osteogenic gene expressions of Cervi Pantotrichum Cornu in MG-63 human osteoblast-like cells. AB - AIMS: The purposes of this study were to determine whether Cervi Pantotrichum Cornu (CPC) has osteogenic activities in human osteoblastic MG-63 cells and to investigate the underlying molecular mechanism. MAIN METHODS: The effects of CPC on alkaline phosphatase activity, collagen synthesis, and calcium deposits were measured. The COL1A1, ALPL, BGLAP, and SPP1 expressions were measured by real time PCR. Phosphorylated MAP kinases (ERK1/2, JNK1/2, p38, ELK1, and cJUN) were studied by western blot analysis. The involvement of MAPK pathway in osteogenic gene expressions was determined by using each selective MAPK inhibitor (PD98059, SP600125, and SB203580). KEY FINDINGS: CPC increased alkaline phosphatase activity, collagen synthesis, and calcium deposits. CPC activated ERK1/2, JNK1/2, p38, and ELK1 phosphorylation except cJUN. CPC increased the COL1A1, ALPL, BGLAP, and SPP1 gene expressions. The elevated COL1A1 and BGLAP expressions were inhibited by PD98059, SP600125 or SB203580. The elevated ALPL expression was blocked by SB203580. The elevated SPP1 expression was inhibited by SP600125 or SB203580. CPC increased COL1A1 and BGLAP expressions via ERK1/2, JNK1/2, and p38 MAPKs pathways and SPP1 expression via JNK1/2 and p38 pathways. p38 pathway is needed for ALPL expression. SIGNIFICANCE: These results imply that MAPK signaling pathway is an indispensable factor for bone matrix genes expression of CPC in MG 63 human osteoblast-like cells. PMID- 24239641 TI - Carvacryl acetate, a derivative of carvacrol, reduces nociceptive and inflammatory response in mice. AB - AIMS: The present study aimed to investigate the potential anti-inflammatory and anti-nociceptive effects of carvacryl acetate, a derivative of carvacrol, in mice. MAIN METHODS: The anti-inflammatory activity was evaluated using various phlogistic agents that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, pro and anti-inflammatory cytokine levels. Evaluation of antinociceptive activity was conducted through acetic acid-induced writhing, hot plate test, formalin test, capsaicin and glutamate tests, as well as evaluation of motor performance on rotarod test. KEY FINDINGS: Pretreatment of mice with carvacryl acetate (75 mg/kg) significantly reduced carrageenan-induced paw edema (P<0.05) when compared to vehicle-treated group. Likewise, carvacryl acetate (75 mg/kg) strongly inhibited edema induced by histamine, serotonin, prostaglandin E2 and compound 48/80. In the peritonitis model, carvacryl acetate significantly decreased total and differential leukocyte counts, and reduced levels of myeloperoxidase and interleukin-1 beta (IL-1beta) in the peritoneal exudate. The levels of IL-10, an anti-inflammatory cytokine, were enhanced by carvacryl acetate. Pretreatment with carvacryl acetate also decreased the number of acetic acid-induced writhing, increased the latency time of the animals on the hot plate and decreased paw licking time in the formalin, capsaicin and glutamate tests. The pretreatment with naloxone did not reverse the carvacryl acetate-mediated nociceptive effect. SIGNIFICANCE: In conclusion, the current study demonstrated that carvacryl acetate exhibited anti-inflammatory activity in mice by reducing inflammatory mediators, neutrophil migration and cytokine concentration, and anti nociceptive activity due to the involvement of capsaicin and glutamate pathways. PMID- 24239642 TI - Early-life seizures in predisposing neuronal preconditioning: a critical review. AB - Although seizures are known to be harmful, recent evidence indicates that they can also lead to adaptations that protect neurons from further insult. For example, a history of two episodes of status epilepticus during a critical period of early development can prolong the time period of resistance to hippocampal injury during the postnatal period. Neonatal seizures may lead to this neuroprotection via a preconditioning mechanism that could be attributed to attenuation of Ca(2+) currents, reduction of inflammation, and induction of survival signaling pathways. Understanding mechanisms underlying neuroprotective preconditioning may elucidate new therapeutic targets and improve outcomes and quality of life for pediatric epilepsy patients. This review will detail the specific cellular and molecular findings involved in neuronal preconditioning predisposed by early-life seizures. PMID- 24239643 TI - Sex-related differences in SLIGRL-induced pruritus in mice. AB - AIMS: Pruritus is a common symptom of skin diseases, and is associated with impaired sleep quality and a considerable reduction in the patient's quality of life. Recently, it was reported that there are sex-specific differences in scratching behavior in chronic pruritus patients. Namely, female chronic pruritus patients scratch more and have significantly more scratch lesions than male patients. However, few animal studies have examined sex-related differences in scratching behavior. Thus, the present work investigated sex-related differences in animal pruritus using pruritogens, which are often used to create experimental animal models of itching. MAIN METHODS: Acute pruritus was induced in ICR mice by a single intradermal injection of histamine, 4-methylhistamine, serotonin, compound 48/80, substance P (SP), or the proteinase-activated receptor-2 (PAR-2) activating peptide SLIGRL-NH2. Chronic pruritus was induced by 5 weeks of the repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to BALB/c mice. KEY FINDINGS: Female mice showed significantly higher scratching counts in SLIGRL-NH2 induced pruritus than male mice. Conversely, there was no obvious sex-related difference in scratching behavior for the other pruritogens examined. SIGNIFICANCE: These results indicate that sex-related differences may exist in the pruritogen-responsive neurons that transmit the itch signal induced by SLIGRL NH2, but not by histamine or 5-HT. PMID- 24239644 TI - Enalapril inhibits nuclear factor-kappaB signaling in intestinal epithelial cells and peritoneal macrophages and attenuates experimental colitis in mice. AB - AIMS: Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, has pleiotropic effects such as anti-inflammatory effects. This study investigated the effect of enalapril on the nuclear factor-kappa B (NF-kappaB) pathway and on experimental colitis. MAIN METHODS: The human intestinal epithelial cell (IEC) line COLO 205 and peritoneal macrophages from C57BL/6 wild-type mice and IL-10 deficient (IL-10(-/-)) mice were prepared and subsequently stimulated with lipopolysaccharide (LPS) alone or LPS plus enalapril. The effect of enalapril on NF-kappaB signaling was examined by western blotting to detect IkappaBalpha phosphorylation/degradation; an electrophoretic mobility shift assay (EMSA) to assess the DNA binding activity of NF-kappaB; and ELISAs to qualify IL-8, TNF alpha, IL-6, and IL-12 production. In in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in wild-type mice and chronic colitis in IL-10(-/-) mice were treated with or without enalapril. Colitis was quantified by histologic scoring, and the phosphorylation of IkappaBalpha in the colonic mucosa was assessed using immunohistochemistry. KEY FINDINGS: Enalapril significantly inhibited LPS-induced IkappaBalpha phosphorylation/degradation, NF-kappaB binding activity, and pro-inflammatory cytokine production in both IEC and peritoneal macrophages. The administration of enalapril significantly reduced the severity of colitis, as assessed based on histology in both murine colitis models. Furthermore, in colon tissue, the up-regulation of IkappaBalpha phosphorylation with colitis induction was attenuated in enalapril-treated mice. SIGNIFICANCE: Enalapril may block the NF-kappaB signaling pathway, inhibit the activation of IECs and macrophages, and attenuate experimental murine colitis by down regulating IkappaBalpha phosphorylation. These findings suggest that enalapril is a potential therapeutic agent for inflammatory bowel disease. PMID- 24239646 TI - Arm injury produces long-term behavioral and neural hypersensitivity in octopus. AB - Cephalopod molluscs are the most neurally and behaviorally complex invertebrates, with brains rivaling those of some vertebrates in size and complexity. This has fostered the opinion that cephalopods, particularly octopuses, may experience vertebrate-like pain when injured. However, it is not known whether octopuses possess nociceptors or if their somatic sensory neurons exhibit sensitization after injury. Here we show that the octopus Abdopus aculeatus expresses nocifensive behaviors including arm autotomy, and displays marked neural hyperexcitability both in injured and uninjured arms for at least 24h after injury. These findings do not demonstrate that octopuses experience pain-like states; instead they add to the minimal existing literature on how cephalopods receive, process, and integrate noxious sensory information, potentially informing and refining regulations governing use of cephalopods in scientific research. PMID- 24239645 TI - Human heart failure: is cell therapy a valid option? AB - The concept of the heart as a terminally differentiated organ incapable of replacing damaged myocytes has been at the center of cardiovascular research and therapeutic development for the past 50 years. The progressive decline in myocyte number with aging and the formation of scarred tissue following myocardial infarction have been interpreted as irrefutable proofs of the post-mitotic characteristics of the adult heart. However, emerging evidence supports a more dynamic view of the myocardium in which cell death and cell restoration are vital components of the remodeling process that governs organ homeostasis, aging and disease. The identification of dividing myocytes throughout the life span of the organisms and the recognition that undifferentiated primitive cells regulate myocyte turnover and tissue regeneration indicate that the heart is a self renewing organ controlled by a compartment of resident stem cells. Moreover, exogenous progenitors of bone marrow origin transdifferentiate and acquire the cardiomyocyte and vascular lineages. This new reality constitutes the foundation of the numerous cell-based clinical trials that have been conducted in the last decade for the treatment of ischemic and non-ischemic cardiomyopathies. PMID- 24239647 TI - Cloning and characterization of the ionotropic GABA receptor subunit rho1 from pig (Sus scrofa). AB - Since human and pig eyes have remarkably anatomical and physiological similitudes swine models have been broadly used for functional studies and therapeutic research. Recently, a GABArho-mediated relaxation of retinal vascularity suggested that GABArho signaling may be used to improve retinal blood flow in vascular-driven impaired vision, and a further molecular characterization of GABArho receptors would be beneficial. However, none of the GABArho type subunits from pigs has been yet cloned; Among the 19 subunits that compose the family of GABAA receptors, rho1-3 subunits are capable of forming homomeric channels. These homomeric receptors are particularly interesting because their pharmacological and kinetic properties are notably different from receptors composed by other GABAA subunits. Here we report the cloning of the GABArho1subunit from the pig and the functional expression of homomeric channels in Xenopus oocytes. The most notable difference found in the pig GABArho1 receptor was the absence of a stretch of 17 amino acids near the amino terminus (R41-V58) conserved in the rat and the human. This sequence has a higher nucleotidic match with the transcript variant 2 of the human GABArho1 subunit. Xenopus oocytes injected with cRNA from the receptor generated currents when exposed to GABA that shared all the characteristics of other GABArho1 subunits in mammals, including its modulation by dopamine. This study will help to increase the knowledge of the genetics of the pig, further the understanding of this important neurotransmitter receptor family and will shed some light in the evolution of these genes among mammals. PMID- 24239648 TI - The role of the 3' region of mammalian gonadotropin beta subunit gene in the luteinizing hormone to chorionic gonadotropin evolution. AB - CGbeta subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. It has evolved by incorporating a previously untranslated region of the LHbeta gene into the reading frame. Although CTP-like sequences are encrypted in the LHbeta genes of several mammals, the CGbeta subunit developed only in primates and equids. To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHbeta gene (boCTP) possesses key characteristics of the human (h) CGbeta-CTP. The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGbeta-CTP, the stretch lacks O-glycans and determinants for circulatory survival. O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation. PMID- 24239649 TI - Adhesive properties of Clostridium perfringens to extracellular matrix proteins collagens and fibronectin. AB - The adhesive properties of Clostridium perfringens to collagens, gelatin, fibronectin (Fn), Fn-prebound collagens, and Fn-prebound gelatin were investigated. C. perfringens could bind to Fn-prebound collagen type II, type III, and gelatin, but not to gelatin or collagens except for collagen type I directly. Recombinant Fn-binding proteins of C. perfringens, rFbpA and rFbpB, were used to examine Fn-mediated bacterial adherence to collagen type I. In the presence of rFbps, C. perfringens adherence to Fn-prebound collagen type I was inhibited in a dose-dependent manner. Fn was not released from the coated collagen type I by the presence of rFbps, and rFbps did not bind to collagen type I. Thus, the inhibition of C. perfringens binding to Fn-prebound collagen type I by rFbps could not be explained by the removal of Fn from collagen or by the competitive binding of rFbps to collagen. Instead, both rFbps were found to bind to C. perfringens. These results suggest the possibility that rFbps may bind to the putative Fn receptor expressed on C. perfringens and competitively inhibit Fn binding to C. perfringens. PMID- 24239651 TI - Blood and Marrow Transplant Clinical Trials Network: progress since the State of the Science Symposium 2007. AB - Outcomes of hematopoietic cell transplantation continue to improve. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from related and unrelated donors. In June 2007, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a State of the Science Symposium (SOSS) in Ann Arbor and identified 11 high priority clinical trials for the network to pursue. This article reviews both the status of those trials and the record of achievement of the BMT CTN as it convenes another SOSS in Grapevine, Texas in February 2014. PMID- 24239650 TI - IL-12hi rapamycin-conditioned dendritic cells mediate IFN-gamma-dependent apoptosis of alloreactive CD4+ T cells in vitro and reduce lethal graft-versus host disease. AB - Rapamycin (RAPA) inhibits the mechanistic target of rapamycin (mTOR), a crucial immune system regulator. Dendritic cells (DC) generated in RAPA (RAPA-DC) enrich for CD4(+) forkhead box p3 (FoxP3(+)) regulatory T cells and induce T cell apoptosis by an unknown mechanism. RAPA-DC also promote experimental allograft survival, yet paradoxically secrete increased IL-12, crucial for the generation of IFN-gamma(+) CD4(+) T cells. However, IFN-gamma is pro-apoptotic and IL-12 driven IFN-gamma inhibits experimental graft-versus-host disease (GVHD). We hypothesized that IL-12(hi) RAPA-DC would facilitate IFN-gamma-mediated apoptosis of alloreactive T cells and, unlike control (CTR)-DC, would reduce lethal GVHD. Following LPS stimulation, RAPA-DC exhibited decreased MHCII and co-stimulatory molecules and contained a significant population of CD86(lo) IL-12(hi) cells. Consistent with our hypothesis, both unstimulated and LPS-stimulated RAPA-DC enhanced alloreactive CD4(+) T cell apoptosis in culture. Augmented T cell apoptosis was ablated by IFN-gamma neutralization or using T cells lacking the IFN-gamma receptor, and it was associated with increased expression of Fas and cleaved caspase 8. DC production or responses to IFN-gamma were not important to increased apoptotic functions of RAPA-DC. LPS-stimulated IL-12p40(-/-) RAPA-DC induced lower levels of T cell apoptosis in culture, which was further decreased with addition of anti-IFN-gamma. Finally, whereas CTR-DC accelerated mortality from GVHD, LPS-treated RAPA-DC significantly prolonged host survival. In conclusion, increased apoptosis of allogeneic CD4(+) T cells induced by LPS stimulated IL-12(hi) RAPA-DC is mediated in vitro through IFN-gamma and in part by increased IL-12 expression. Enhanced production of IL-12, the predominant inducer of IFN-gamma by immune cells, is a probable mechanism underlying the capacity of LPS-treated RAPA-DC to reduce GVHD. PMID- 24239653 TI - A Bayesian filtering approach to incorporate 2D/3D time-lapse confocal images for tracking angiogenic sprouting cells interacting with the gel matrix. AB - We present a new approach to incorporating information from heterogeneous images of migrating cells in 3D gel. We study 3D angiogenic sprouting, where cells burrow into the gel matrix, communicate with other cells and create vascular networks. We combine time-lapse fluorescent images of stained cell nuclei and transmitted light images of the background gel to track cell trajectories. The nuclei images are sampled less frequently due to photo toxicity. Hence, 3D cell tracking can be performed more reliably when 2D sprout profiles, extracted from gel matrix images, are effectively incorporated. We employ a Bayesian filtering approach to optimally combine the two heterogeneous images with different sampling rates. We construct stochastic models to predict cell locations and sprout profiles and condition the likelihood of nuclei location by the sprout profile. The conditional distribution is non-Gaussian and the cell dynamics is non-linear. To jointly update cell and sprout estimates, we use a Rao-Blackwell particle filter. Simulation and experimental results show accurate tracking of multiple cells along with sprout formation, demonstrating synergistic effects of incorporating the two types of images. PMID- 24239652 TI - Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-kappaB/activator protein-1 signaling pathways: a possible role in atherosclerosis. AB - Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200MUg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-kappaB/AP-1 transactivation in macrophages. In addition, the production of TNF-alpha and IL-1beta was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-kappaB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-kappaB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-alpha and IL-1beta was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease. PMID- 24239654 TI - 137Cs vertical migration in a deciduous forest soil following the Fukushima Dai ichi Nuclear Power Plant accident. AB - The large amount of (137)Cs deposited on the forest floor because of the Fukushima Dai-ichi Nuclear Power Plant accident represents a major potential long term source for mobile (137)Cs. To investigate (137)Cs mobility in forest soils, we investigated the vertical migration of (137)Cs through seepage water, using a lysimetric method. The study was conducted in a deciduous forest soil over a period spanning 2 month to 2 y after the Fukushima nuclear accident. Our observations demonstrated that the major part of (137)Cs in the litter layer moved into the mineral soil within one year after the accident. On the other hand, the topsoil prevented migration of (137)Cs, and only 2% of (137)Cs in the leachate from litter and humus layer penetrated below a 10 cm depth. The annual migration below a 10 cm depth accounted for 0.1% of the total (137)Cs inventory. Therefore, the migration of (137)Cs by seepage water comprised only a very small part of the total (137)Cs inventory in the mineral soil, which was undetectable from the vertical distribution of (137)Cs in the soil profile. In the present and immediate future, most of the (137)Cs deposited on the forest floor will probably remain in the topsoil successively, although a small but certain amount of bioavailable (137)Cs exists in forest surface soil. PMID- 24239655 TI - 7Be, 210Pb and 137Cs concentrations in cloud water. AB - Cloud water was sampled during 8 months, in 2008 and 2009, at the puy de Dome high-altitude atmospheric research station (France). The concentrations of (7)Be and (210)Pb, both naturally occurring radionuclides, and (137)Cs of anthropogenic origin, were determined. Those values are useful for a better knowledge of the aftermath cloud deposition and more generally for wet deposition assessment of radionuclides. This is of primary interest in case of a nuclear accident, especially considering (137)Cs deposition, both for high-altitude locations that are regularly embedded by clouds and also for lowlands where fog can occur. The (7)Be and (210)Pb average activity concentrations in cloud water found were 1.9+/ 0.11 mBq m(-3) air and 140+/-10 MUBq m(-3) air, respectively. For (137)Cs, the average concentration was 0.14+/-0.02 MUBq m(-3) air. This very low-level is representative of the long term post-accidental background level. Indeed, for the studied period, the last accidental (137)Cs release was that of Chernobyl accident, in April 1986. To our knowledge this is the first data about (137)Cs reference level determination in cloud water. The comparison between cloud water and rain water concentrations showed a ratio cloud/rain ranging between 3.4 and 8.1, in agreement with previous studies performed on inorganic compounds. Scavenging efficiencies of aerosols by cloud droplets were also calculated with the additional aerosol concentrations routinely measured at the station and were quite low (0.13-0.40) compared to what has previously been observed for inorganic soluble ions. PMID- 24239656 TI - Nuclear rDNA pseudogenes in Chagas disease vectors: evolutionary implications of a new 5.8S+ITS-2 paralogous sequence marker in triatomines of North, Central and northern South America. AB - A pseudogene, paralogous to rDNA 5.8S and ITS-2, is described in Meccus dimidiata dimidiata, M. d. capitata, M. d. maculippenis, M. d. hegneri, M. sp. aff. dimidiata, M. p. phyllosoma, M. p. longipennis, M. p. pallidipennis, M. p. picturata, M. p. mazzottii, Triatoma mexicana, Triatoma nitida and Triatoma sanguisuga, covering North America, Central America and northern South America. Such a nuclear rDNA pseudogene is very rare. In the 5.8S gene, criteria for pseudogene identification included length variability, lower GC content, mutations regarding the functional uniform sequence, and relatively high base substitutions in evolutionary conserved sites. At ITS-2 level, criteria were the shorter sequence and large proportion of insertions and deletions (indels). Pseudogenic 5.8S and ITS-2 secondary structures were different from the functional foldings, different one another, showing less negative values for minimum free energy (mfe) and centroid predictions, and lower fit between mfe, partition function, and centroid structures. A complete characterization indicated a processed pseudogenic unit of the ghost type, escaping from rDNA concerted evolution and with functionality subject to constraints instead of evolving free by neutral drift. Despite a high indel number, low mutation number and an evolutionary rate similar to the functional ITS-2, that pseudogene distinguishes different taxa and furnishes coherent phylogenetic topologies with resolution similar to the functional ITS-2. The discovery of a pseudogene in many phylogenetically related species is unique in animals and allowed for an estimation of its palaeobiogeographical origin based on molecular clock data, inheritance pathways, evolutionary rate and pattern, and geographical spread. Additional to the technical risk to be considered henceforth, this relict pseudogene, designated as "ps(5.8S+ITS-2)", proves to be a valuable marker for specimen classification, phylogenetic analyses, and systematic/taxonomic studies. It opens a new research field, Chagas disease epidemiology and control included, given its potential relationships with triatomine fitness, behaviour and adaptability. PMID- 24239657 TI - Forced exercise before or after induction of 6-OHDA-mediated nigrostriatal insult does not mitigate behavioral asymmetry in a hemiparkinsonian rat model. AB - Studies on exercise before and after toxin-induced hemiparkinsonism have reported promising findings in terms of amelioration of motor asymmetry in adult, 6 hydroxydopamine (6-OHDA) rats. However, recent studies have had more mixed results. Therefore, the purpose of this study was to further explore the notion of exercise, in particular forced exercise, as a potential neuroprotective therapy when implemented before and after 6-OHDA hemiparkinsonism. To explore this, two experiments were conducted: Experiment 1 - exercise before a 6-OHDA lesion; and, Experiment 2 - exercise after a 6-OHDA lesion. In Experiment 1, rats were randomly assigned into one of the two 4-week experimental conditions, a forced exercise condition and a non-exercise control condition. Then, after the experimental conditions rats were injected with 6-OHDA into the right medial forebrain bundle. In Experiment 2, rats were first injected with 6-OHDA and were then randomly assigned into one of the two 4-week experimental groups, a forced exercise group and a non-exercise control group. Outcomes in both experiments did not show any differences in terms of motor behavioral tests (i.e., apomorphine rotations, forelimb placement asymmetry, exploratory rearing) between the forced exercise and sedentary control groups. Based on our results and in light of the body of literature, it is possible that the stress of shock-motivated forced running utilized in this study may have canceled beneficial behavioral effects. Additionally, it is possible that the one-week delay in the forced exercise protocol implementation in Experiment 2 may have prevented behavioral rescue. PMID- 24239659 TI - Aortic stiffness for cardiovascular risk prediction: just measure it, just do it! PMID- 24239658 TI - Enhydrina schistosa (Elapidae: Hydrophiinae) the most dangerous sea snake in Sri Lanka: three case studies of severe envenoming. AB - Sea snakes are highly venomous and inhabit tropical waters of the Indian and Pacific Oceans. Enhydrina schistosa is a common species of sea snake that lives in the coastal waters, lagoons, river mouths and estuaries from the Persian Gulf through Sri Lanka and to Southeast Asia. It is considered one of the most aggressive sea snakes in Sri Lanka where fishermen and people wading are at high risk. However, sea snake bites are rarely reported. In this report, we describe three cases where E. schistosa was the offending species. These three patients presented to two hospitals on the west coast of Sri Lanka within the course of 14 months from November 2011 with different degrees of severity of envenoming. The first patient was a 26-year-old fisherman who developed severe myalgia with very high creatine kinase (CK) levels lasting longer than 7 days. The second patient was a 32-year-old fisherman who developed gross myoglobinuria, high CK levels and hyperkalaemia. Both patients recovered and their electromyographic recordings showed myopathic features. The nerve conduction and neuromuscular transmission studies were normal in both patients suggesting primary myotoxic envenoming. The third patient was a 41-year-old man who trod on a sea snake in a river mouth and developed severe myalgia seven hours later. He had severe rhabdomyolysis and died three days later due to cardiovascular collapse. In conclusion, we confirm that E. schistosa is a deadly sea snake and its bite causes severe rhabdomyolysis. PMID- 24239660 TI - Left ventricular remodeling and 1-year clinical follow-up of the REOPEN-AMI trial. PMID- 24239661 TI - The year in acute coronary syndrome. PMID- 24239662 TI - Impact of smoking on long-term outcomes in patients with atherosclerotic vascular disease treated with aspirin or clopidogrel: insights from the CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events). AB - OBJECTIVES: The goal of this study was to investigate the differential efficacy of clopidogrel or aspirin monotherapy according to smoking status in patients with atherosclerotic vascular disease. BACKGROUND: Smoking enhances clopidogrel induced platelet inhibition, which may explain the higher relative benefit among smokers observed in trials evaluating dual antiplatelet therapy. Whether smoking has an impact on clinical outcomes in patients requiring a single antiplatelet agent remains unknown. METHODS: This was a post-hoc analysis of the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trial that compared clopidogrel and aspirin monotherapy in patients (N = 19,184) with atherosclerotic vascular disease. RESULTS: Current smokers (n = 5,688) had an increased risk of ischemic events compared with never smokers (n = 4,135; hazard ratio [HR]: 1.24 [95% confidence interval (CI): 1.08 to 1.42]) and ex-smokers (n = 9,381; HR: 1.32 [95% CI: 1.18 to 1.47]) (p < 0.001). Clopidogrel was associated with a reduction in ischemic events among current smokers (8.3% vs. 10.8%; HR: 0.76 [95% CI: 0.64 to 0.90]), whereas no benefit over aspirin was seen in the combined group of ex-smokers/never-smoked patients (10.4% vs. 10.6%; HR: 0.99 [95% CI: 0.89 to 1.10]; p = 0.01 for interaction). Among current smokers, clopidogrel also reduced myocardial infarction, vascular death, and death from any cause compared with aspirin. No interaction between smoking status and study treatment was observed for bleeding events. CONCLUSIONS: In a post-hoc analysis of the CAPRIE population, current smokers appeared to have enhanced benefit with clopidogrel therapy for secondary prevention compared with aspirin. These results should be considered hypothesis generating for future prospective studies assessing the impact of specific platelet-inhibiting strategies according to smoking status. PMID- 24239663 TI - Paradoxical coronary embolisms as a presentation of hereditary hemorrhagic telangiectasia. PMID- 24239665 TI - Coil embolization for spontaneous rupture of the left internal mammary artery secondary to lupus vasculitis. PMID- 24239664 TI - Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. AB - OBJECTIVES: The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors. BACKGROUND: Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups. METHODS: We undertook a systematic review and obtained individual participant data from 16 studies. Study specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. RESULTS: Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p < 0.001) for coronary heart disease, 1.54 (95% CI: 1.34 to 1.78; p < 0.001) for stroke, and 1.45 (95% CI: 1.30 to 1.61; p < 0.001) for CVD. Associations stratified according to sex, diabetes, and hypertension were similar but decreased with age (1.89, 1.77, 1.36, and 1.23 for age <=50, 51 to 60, 61 to 70, and >70 years, respectively; pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor of coronary heart disease (HR: 1.23 [95% CI: 1.11 to 1.35]; p < 0.001), stroke (HR: 1.28 [95% CI: 1.16 to 1.42]; p < 0.001), and CVD events (HR: 1.30 [95% CI: 1.18 to 1.43]; p < 0.001). Reclassification indices showed that the addition of aPWV improved risk prediction (13% for 10-year CVD risk for intermediate risk) for some subgroups. CONCLUSIONS: Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management. PMID- 24239666 TI - The effect of the MDCK cell selected neuraminidase D151G mutation on the drug susceptibility assessment of influenza A(H3N2) viruses. AB - Propagation of influenza A(H3N2) viruses in MDCK cells has been associated with the emergence of neuraminidase (NA) variants carrying a change at residue 151. In this study, the pyrosequencing assay revealed that ~90% of A(H3N2) virus isolates analyzed (n=150) contained more than one amino acid variant (D/G/N) at position 151. Susceptibilities of the virus isolates to zanamivir and oseltamivir were assessed using the chemiluminescent and fluorescent NA inhibition (NI) assays. In the chemiluminescent assay, which utilizes NA-Star(r) substrate, up to 13-fold increase in zanamivir-IC50 was detected for isolates containing a high proportion (>50%) of the G151 NA variant. However, an increase in zanamivir-IC50s was not seen in the fluorescent assay, which uses MUNANA as substrate. To investigate this discrepancy, recombinant NAs (rNAs) were prepared and tested in both NI assays. Regardless of the assay used, the zanamivir-IC50 for the rNA G151 was much greater (>1500-fold) than that for rNA D151 wild-type. However, zanamivir resistance conferred by the G151 substitution was masked in preparations containing the D151 NA which had much greater activity, especially against MUNANA. In conclusion, the presence of NA D151G variants in cell culture-grown viruses interferes with drug susceptibility assessment and therefore measures need to be implemented to prevent their emergence. PMID- 24239667 TI - Targeted therapy in metastatic renal carcinoma. AB - BACKGROUND: Advanced renal cell carcinoma is one of the most treatment-resistant malignancies to conventional cytotoxic chemotherapy. The development of new targeted therapy was result of understanding biological pathways underlying renal cell carcinoma. Our objective is to provide an overview of current therapies in metastatic renal cell carcinoma. METHODS: MEDLINE/PUBMED was queried in December 2012 to identify abstracts, original and review articles. The research was conducted using the following words: "metastatic renal cell carcinoma" and "target therapy". Phase II and Phase III clinical trials were included followed FDA approval. Total of 40 studies were eligible for review. CONCLUSION: The result of this review shows benefit of these target drugs in tumor burden, increase progression-free and overall survival and improvement the quality of life compared with previous toxic immunotherapy, although complete response remains rare. PMID- 24239668 TI - The environmental regulation of maturation in goldfish, Carassius auratus: effects of various LED light spectra. AB - While there have been a number of studies on the effects of photoperiod and duration of light and dark exposure, much less information is available on the importance of light intensity. This study investigated the effects of exposure of goldfish, Carassius auratus exposed to white fluorescent bulbs, and red (peak at 630nm), and green (530nm) light emitting diodes (LEDs) at approximately 0.9W/m(2) (12-h light:12-h dark) for four months on a number of hormones of the hypothalamus-pituitary-gonad (HPG) axis, in vivo and in vitro. We investigated the effects of native GnRH molecules (gonadotropin-releasing hormones; salmon GnRH, sGnRH; and chicken GnRH-II, cGnRH-II), gonadotropin hormones (GTHalpha; follicle-stimulating hormone, FSH-beta; luteinizing hormone, LH-beta2), kisspeptin 1 (Kiss1) and G protein-coupled receptor 54 (GPR54) mRNA levels. Furthermore, we measured LH and 17alpha-hydroxypregnenolone levels in plasma and we performed gonad histological observations. GnRHs, Kiss1, GPR54 and GTH mRNA and plasma LH and 17alpha-hydroxypregnenolone levels in the in vivo and in vitro groups exposed to green LEDs were significantly higher than the other groups. Histological analysis revealed the presence of oocytes in the yolk stage in fish exposed to green light. These results suggest that green wavelengths regulate the HPG axis and enhance sexual maturation in goldfish. PMID- 24239669 TI - Short-term time course of liver metabolic response to acute handling stress in rainbow trout, Oncorhynchus mykiss. AB - To elucidate the short-term time-course of liver metabolic response in rainbow trout to acute handling stress we subjected rainbow trout to 5min chasing and obtained samples 0 to 480min post-stress. Levels of cortisol, glucose and lactate were measured in plasma, whereas metabolite levels, enzyme activities, mRNA abundance of parameters related to energy metabolism, and glucocorticoid receptors were assessed in liver. Acute stress affected many parameters related to energy metabolism, with most of them turning back to normal levels after 480min. In general, the present results support the existence of two stages in the short-term time-course of metabolic response to handling stress. A first stage occurring few minutes post-stress (15-45min), was characterized by increased mobilization of liver glycogen resulting in increased production of endogenous glucose, reduced use of exogenous glucose and reduced lipogenic potential. A second stage, occurring 60-120min post-stress onwards was characterized by the recovery of liver glycogen levels, the increased capacity of liver for releasing glucose, and the recovery of lipogenic capacity whereas no changes were noted in gluconeogenic potential, which probably needs longer time periods to become enhanced. PMID- 24239670 TI - Cold acclimation of NaCl secretion in a eurythermic teleost: mitochondrial function and gill remodeling. AB - Active chloride secretion, measured as short-circuit current (Isc) in ionocytes of opercular epithelia (OE) in the eurythermic, euryoxic, and euryhaline killifish or mummichog (Fundulus heteroclitus) was studied in cold (5 degrees C) and warm (20 degrees C) acclimated fish to determine if homeoviscous adaptation aided chloride secretion in the cold. Isolated opercular epithelia were cooled from 30 degrees C to 0.2 degrees C for warm and cold acclimated fish; from 30 to 8 degrees C, Isc decreased with Q10=1.68 for warm and Q10=1.56 for cold acclimated tissues. By Arrhenius plots, there is a critical temperature, 8 degrees C, below which aerobic Isc decreased sharply (Q10=6.90 for warm and 4.23 for cold acclimated tissues), suggesting a shift in mitochondrial efficiency of oxidative phosphorylation. In anaerobic conditions (0.5mM NaCN; N2 saturation), chloride transport continued at a lower rate, and Isc decrease with cooling below 8 degrees C was less pronounced (Q10=2.95 for warm and 3.08 for cold), suggesting a shift in transporter function in plasma membrane. Under anaerobic conditions, NaCl secretion at 20 degrees C was reversibly inhibited by hypotonic shock, indicating normal regulation of transport. Chloride secretion in warm-acclimated fish was supported mostly (75% at 20 degrees C) by aerobic metabolism, whereas that for cold-acclimated fish was lower (55% at 20 degrees C), suggesting a greater reliance on anaerobic metabolism in the cold. Once acclimated to cold, ionocytes may be temporarily incapable of increasing their aerobic ATP supply, even when warmed to 30 degrees C. In cold acclimated fish there was increased polyunsaturated fatty acid composition of gill epithelium (consistent with homeoviscous adaptation) and gill remodeling, wherein epithelial cells filled the interlamellar space (interlamellar cell mass, ILCM) by as much as 70%, thus increasing diffusion distance against passive ion gain. Most ionocytes in these thickened epithelial masses became taller, still connecting basal lamina with the environment, consistent with the continuing transport rates at low temperatures. Whereas the low aerobic scope of cold-acclimated fish and thickened gill epithelium is appropriate to winter inactivity, metabolic depression and anaerobiosis, the large aerobic scope of warm-acclimated fish favors active foraging at high temperatures. PMID- 24239672 TI - Etifoxine analgesia in experimental monoarthritis: a combined action that protects spinal inhibition and limits central inflammatory processes. AB - Inflammatory and degenerative diseases of the joint are major causes of chronic pain. Long-lasting pain symptoms are thought to result from a central sensitization of nociceptive circuits. These processes include activation of microglia and spinal disinhibition. Using a monoarthritic rat model of pain, we tried to potentiate neural inhibition by using etifoxine (EFX), a nonbenzodiazepine anxiolytic that acts as an allosteric-positive modulator of gamma-aminobutyric acid type A (GABAA) receptor function. Interestingly, EFX also can bind to the mitochondrial translocator protein (TSPO) complex and stimulate the synthesis of 3alpha-reduced neurosteroids, the most potent positive allosteric modulator of GABAA receptor function. Here we show that a curative and a preventive treatment with 50mg/kg of EFX efficiently reduced neuropathic pain symptoms. In the spinal cord, EFX analgesia was accompanied by a reduction in microglial activation and in the levels of proinflammatory mediators. Using electrophysiological tools, we found that EFX treatment not only amplified spinal GABAergic inhibition, but also prevented prostaglandin E2-induced glycinergic disinhibition and restored a "normal" spinal pain processing. Because EFX is already distributed in several countries under the trade name of Stresam for its anxiolytic actions in humans, new clinical trials are now required to further extend its therapeutic indications as pain killer. PMID- 24239671 TI - The gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization induced by partial infraorbital nerve transection in rats. AB - Glial cells are being increasingly implicated in mechanisms underlying pathological pain, and recent studies suggest glial gap junctions involving astrocytes may contribute. The aim of this study was to examine the effect of a gap junction blocker, carbenoxolone (CBX), on medullary dorsal horn (MDH) nociceptive neuronal properties and facial mechanical nociceptive behavior in a rat trigeminal neuropathic pain model involving partial transection of the infraorbital nerve (p-IONX). p-IONX produced facial mechanical hypersensitivity reflected in significantly reduced head withdrawal thresholds that lasted for more than 3weeks. p-IONX also produced central sensitization in MDH nociceptive neurons that was reflected in significantly increased receptive field size, reduction of mechanical activation threshold, and increases in noxious stimulation-evoked responses. Intrathecal CBX treatment significantly attenuated the p-IONX-induced mechanical hypersensitivity and the MDH central sensitization parameters, compared to intrathecal vehicle treatment. These results provide the first documentation that gap junctions may be critically involved in orofacial neuropathic pain mechanisms. PMID- 24239673 TI - Past 140-year environmental record in the northern South China Sea: evidence from coral skeletal trace metal variations. AB - About 140-year changes in the trace metals in Porites coral samples from two locations in the northern South China Sea were investigated. Results of PCA analyses suggest that near the coast, terrestrial input impacted behavior of trace metals by 28.4%, impact of Sea Surface Temperature (SST) was 19.0%, contribution of war and infrastructure were 14.4% and 15.6% respectively. But for a location in the open sea, contribution of War and SST reached 33.2% and 16.5%, while activities of infrastructure and guano exploration reached 13.2% and 14.7%. While the spatiotemporal change model of Cu, Cd and Pb in seawater of the north area of South China Sea during 1986-1997 were reconstructed. It was found that in the sea area Cu and Cd contaminations were distributed near the coast while areas around Sanya, Hainan had high Pb levels because of the well-developed tourism related activities. PMID- 24239674 TI - Mathematical analysis of an age-structured model for malaria transmission dynamics. AB - A new deterministic model for assessing the role of age-structure on the transmission dynamics of malaria in a community is designed. Rigorous qualitative analysis of the model reveals that it undergoes the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model co-exists with a stable endemic equilibrium when the associated reproduction number (denoted by R0) is less than unity. It is shown that the backward bifurcation phenomenon is caused by the malaria-induced mortality in humans. A special case of the model is shown to have a unique endemic equilibrium whenever the associated reproduction threshold exceeds unity. Further analyses reveal that adding age-structure to a basic model for malaria transmission in a community does not alter the qualitative dynamics of the basic model, with respect to the existence and asymptotic stability of the associated equilibria and the backward bifurcation property of the model. Numerical simulations of the model show that the cumulative number of new cases of infection and malaria-induced mortality increase with increasing average lifespan and birth rate of mosquitoes. PMID- 24239675 TI - Estimation of statistical binding properties of ligand population during in vitro selection based on population dynamics theory. AB - During in vitro selection process, it is very valuable to monitor the binding properties of the ligand population in real time, particularly the population average of the association constant in the population. If this monitoring can be realized, the selection process can be controlled in a rational way. In this paper, we present a simple method to estimate the binding properties of the ligand population during in vitro selection. The framework of the method is as follows. First, the number of all the collected ligand molecules, which are eluted after incubation and washing, is measured. Ideally, this number corresponds to the number of all the ligand molecules bound with the target receptor or other materials in a test tube. This measurement is performed through several successive rounds of selection. Second, the measured numbers of molecules are subjected to a theoretical analysis, based on the mathematical theory of population dynamics in the selection process. Then, we can estimate the probability density of the binding free energy in the ligand population. The validity of our method was confirmed by several computer simulations based on a physicochemical model. PMID- 24239676 TI - No Pasaran! Role of the axon initial segment in the regulation of protein transport and the maintenance of axonal identity. AB - The transmission of information in the brain depends on the highly polarized architecture of neurons. A number of cellular transport processes support this organization, including active targeting of proteins and passive corralling between compartments. The axon initial segment (AIS), which separates the somatodendritic and axonal compartments, has a key role in neuronal physiology, as both the initiation site of action potentials and the gatekeeper of the axonal arborization. Over the years, the AIS main components and their interactions have been progressively unraveled, as well as their role in the AIS assembly and maintenance. Two mechanisms have been shown to contribute to the regulation of protein transport at the AIS: a surface diffusion barrier and an intracellular traffic filter. However, a molecular understanding of these processes is still lacking. In the view of recent results on the AIS cytoskeleton structure, we will discuss how a better knowledge of the AIS architecture can help understanding its role in the regulation of protein transport and the maintenance of axonal identity. PMID- 24239677 TI - A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery. AB - Three-dimensional (3-D) open-channeled scaffolds of biopolymers are a promising candidate matrix for tissue engineering. When scaffolds have the capacity to deliver bioactive molecules the potential for tissue regeneration should be greatly enhanced. In order to improve drug-delivery capacity, we exploit 3-D poly(lactic acid) (PLA) scaffolds by creating microporosity within the scaffold network. Macroporous channeled PLA with a controlled pore configuration was obtained by a robotic dispensing technique. In particular, a room temperature ionic liquid (RTIL) bearing hydrophilic counter-anions, such as OTf and Cl, was introduced to the biopolymer solution at varying ratios. The RTIL-biopolymer slurry was homogenized by ultrasonication, and then solidified through the robotic dispensing process, during which the biopolymer and RTIL formed a bicontinuous interpenetrating network. After ethanol wash-out treatment the RTIL was completely removed to leave highly microporous open channels throughout the PLA network. The resultant pore size was observed to be a few micrometers (average 2.43 MUm) and microporosity was determined to be ~ 70%. The microporous surface was also shown to favor initial cell adhesion, stimulating cell anchorage on the microporous structure. Furthermore, in vivo tissue responses assessed in rat subcutaneous tissue revealed good tissue compatibility, with minimal inflammatory reactions, while gathering a larger population of fibroblastic cells than the non-microporous scaffolds, and even facilitating invasion of the cells within the microporous structure. The efficacy of the micropore networks generated within the 3-D scaffolds in loading and releasing therapeutic molecules was addressed using antibiotic sodium ampicillin and protein cytochrome C as model drugs. The microporous scaffolds exhibited significantly enhanced drug loading capacity: 4-5 times increase in ampicillin and 9-10 times increase in cytochrome C compared to the non-microporous scaffolds. The release of ampicillin loaded within the microporous scaffolds was initially fast (~ 85% for 1 week), and was then slowed down, showing a continual release up to a month. On the other hand, cytochrome C was shown to release in a highly sustainable manner over a month, without showing an initial burst release effect. This study provides a novel insight into the generation of 3-D biopolymer scaffolds with high performance in loading and delivery of biomolecules, facilitated by the creation of microporous channels through the scaffold network. The capacity to support tissue cells while in situ delivering drug molecules makes the current scaffolds potentially useful for therapeutic tissue engineering. PMID- 24239678 TI - Brain norepinephrine identified by mass spectrometry is associated with reproductive status of females of the linden bug Pyrrhocoris apterus. AB - Several biogenic amines, including controversial presence of norepinephrine (NE), were identified by the high performance liquid chromatography equipped with electrospray ionisation mass spectrometry in brain complexes of adult females of Pyrrhocoris apterus. Quantitative analysis was performed by the high performance liquid chromatography coupled to electrochemical detector. Levels of NE, dopamine (DA), octopamine (OA) and 5-hydroxytryptamine (5-HT) in brain complexes were measured in reproductive vs. diapause females. In field collected samples, levels of NE and DA were significantly higher in reproductive (May) than in non reproductive (Sep, Oct, Feb) females. In laboratory females, NE is higher in long day photoperiod (reproduction) than in short day photoperiod (diapause) already from the first week of the adult age, while DA shows differences between the two contrasting photoperiods only from the second week of the adult age. No association between reproductive status and levels of OA and 5-HT was found. PMID- 24239680 TI - Kisspeptin regulates the hypothalamus-pituitary-gonad axis gene expression during sexual maturation in the cinnamon clownfish, Amphiprion melanopus. AB - Kisspeptins (Kiss) have been recognized as potent regulators of reproduction in teleosts, and Kiss is suggested to be a key regulator of the hypothalamus pituitary-gonad axis (HPG). However, its regulatory role on reproduction in fish remains unclear. Therefore, to investigate the role of Kiss on fish reproduction, this study aimed to test differences in the hormones of the HPG axis, Kiss as neuropeptides, and sex steroids on the sexual maturation of paired cinnamon clownfish, Amphiprion melanopus, following treatment with Kiss. We investigated the actions of sex maturation hormones, including HPG axis hormones and sex steroid hormones, such as gonadotropin-releasing hormones, gonadotropin hormones (GTHs), GTH receptors, estrogen receptors, and vitellogenin in the pituitary, gonads, and liver following treatment with Kiss. The expression levels of HPG axis genes increased after the Kiss injection. In addition, the levels of plasma 17alpha-hydroxypregnenolone, estradiol-17beta, and 11-ketotestosterone increased. These results support the hypothesis that Kiss play important roles in the regulation of the HPG axis and are most likely involved in gonadal development and sexual maturation in cinnamon clownfish. PMID- 24239679 TI - Sex-specific expression and localization of aromatase and its regulators during embryonic and larval development of Atlantic salmon. AB - The products of dax1, foxl2a and mis have each been shown to have proliferative and/or differentiative activities during mammalian organogenesis. These factors also play a role in regulating the biosynthesis of estrogen, particularly by modulating the activity of aromatase cyp19a. We demonstrate the transcription and translation of these genes during salmon embryogenesis. We were able to track sex specific differences in these processes through accurate determination of the sex of each embryo and larva examined from genotyped microsatellites. We detected sex and stage-specific immunolabeling of the embryonic gut, kidney, gonads, neural cord and skeletal muscle by DAX-1, FOXL2A and MIS. These results indicate the potential of these factors to mediate proliferation and/or differentiation programs during development of these tissues. As well, immunolabeling of skeletal muscle by CYP19B1 throughout the study reveals probable neurogenic activity associated with peripheral radial glial cells and the growing embryonic musculature. PMID- 24239681 TI - Luminescent mesoporous nanoreservoirs for the effective loading and intracellular delivery of therapeutic drugs. AB - Development of biocompatible and multifunctional nanocarriers is important for the therapeutic efficacy of drug molecules in the treatment of disease and tissue repair. A novel nanocarrier of luminescent hollowed mesoporous silica (L-hMS) was explored for the loading and controlled delivery of drugs. For the synthesis of L hMS, self-activated luminescence hydroxyapatite (LHA) was used as a template. Different thicknesses (~ 7-62 nm) of mesoporous silica shell were obtained by varying the volume of silica precursor and the subsequent removal of the LHA core, which resulted in hollow-cored (size of ~ 40 nm * 10 nm) mesoporous silica nanoreservoirs, L-hMS. While the silica shell provided a highly mesoporous structure, enabling an effective loading of drug molecules, the luminescent property of LHA was also well preserved in both the silica-shelled and the hollow cored nanocarriers. Doxorubicin (DOX), used as a model drug, was shown to be effectively loaded onto the mesopore structure and within the hollow space of the nanoreservoir. The DOX release was fairly pH-dependent, occurring more rapidly at pH 5.3 than at pH 7.4, and a long-term sustainable delivery over the test period of 2weeks was observed. The nanoreservoir exhibited favorable cell compatibility with low cytotoxicity and excellent cell uptake efficiency (over 90%). Treatment of HeLa cells with DOX-loaded L-hMS elicited a sufficient degree of biological efficacy of DOX, as confirmed in the DOX-induced apoptotic behaviors, including stimulation in caspase-3 expression, and was even more effective than the direct DOX treatment. Overall, the newly developed L-hMS nanoreservoirs may be potentially useful as a multifunctional (luminescent, mesoporous and biocompatible) carrier system to effectively load and sustainably deliver small molecules, including anticancer drugs. PMID- 24239682 TI - Identifying colon cancer risk modules with better classification performance based on human signaling network. AB - Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. PMID- 24239683 TI - Improving cancer control through a community-based cancer awareness initiative. AB - OBJECTIVE: To assess the impact of the Cancer Research UK Cancer Awareness Roadshow on intentions to change health behaviours and use local health services related to cancer. METHOD: Feedback forms from visitors to three Roadshows collected data on anticipated lifestyle changes and health service use following their visit to the Roadshow. Demographic predictors of intentions were investigated. RESULTS: A total of 6009 individuals completed a feedback form. On average, respondents intended to make between two and three (2.55; SD=1.77) lifestyle changes, and use between none and one (0.59; SD=0.77) local health services following their visit. Multivariable analysis showed that age (p=0.001), ethnicity (p=0.006), and occupation (p=0.043) were significant predictors of anticipated lifestyle changes. Anticipated health service use was higher among men (p=0.001), younger groups (p<0.001), and smokers (p<0.001). Overall effects of ethnicity (p=0.001) and occupation (p<0.001) on anticipated health service use were also observed. Post-hoc analyses indicated stronger effects of the Roadshow among disadvantaged groups. CONCLUSION: High levels of anticipated health behaviour change and health service use were observed among Roadshow visitors. Disadvantaged groups such as lower socioeconomic groups, ethnic minorities, and smokers showed particularly high levels of intention. A more in-depth evaluation of the Roadshow is warranted. PMID- 24239685 TI - Reorganizing life: A qualitative study of fathers' lived experience in the 3 years subsequent to the very preterm birth of their child. AB - This is the second part of a study that is following eight Swedish fathers of very preterm children using qualitative interviews. The aim was to illuminate fathers' lived experience of the 3 years since the birth of their very preterm child using a hermeneutic phenomenological method. The fathers described their lived experience as a process of reorganizing life, which constituted the overarching theme. They described a journey from the past to the present in which they adapted ordinary family life. The sub-themes identified were struggling to endure, experiencing empowerment, and building a secure base. The results may serve as a basis for neonatal staff to optimize care for both fathers and mothers during the child's hospitalization, as well as subsequent to their discharge. PMID- 24239684 TI - Mechanisms of cryoablation: clinical consequences on malignant tumors. AB - While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer, which while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer. PMID- 24239686 TI - Structure-function studies on jaburetox, a recombinant insecticidal peptide derived from jack bean (Canavalia ensiformis) urease. AB - BACKGROUND: Ureases are metalloenzymes involved in defense mechanisms in plants. The insecticidal activity of Canavalia ensiformis (jack bean) ureases relies partially on an internal 10kDa peptide generated by enzymatic hydrolysis of the protein within susceptible insects. A recombinant version of this peptide, jaburetox, exhibits insecticidal, antifungal and membrane-disruptive properties. Molecular modeling of jaburetox revealed a prominent beta-hairpin motif consistent with either neurotoxicity or pore formation. METHODS: Aiming to identify structural motifs involved in its effects, mutated versions of jaburetox were built: 1) a peptide lacking the beta-hairpin motif (residues 61-74), JbtxDelta-beta; 2) a peptide corresponding the N-terminal half (residues 1-44), Jbtx N-ter, and 3) a peptide corresponding the C-terminal half (residues 45-93), Jbtx C-ter. RESULTS: 1) JbtxDelta-beta disrupts liposomes, and exhibited entomotoxic effects similar to the whole peptide, suggesting that the beta hairpin motif is not a determinant of these biological activities; 2) both Jbtx C ter and Jbtx N-ter disrupted liposomes, the C-terminal peptide being the most active; and 3) while Jbtx N-ter persisted to be biologically active, Jbtx C-ter was less active when tested on different insect preparations. Molecular modeling and dynamics were applied to the urease-derived peptides to complement the structure-function analysis. MAJOR CONCLUSIONS: The N-terminal portion of the Jbtx carries the most important entomotoxic domain which is fully active in the absence of the beta-hairpin motif. Although the beta-hairpin contributes to some extent, probably by interaction with insect membranes, it is not essential for the entomotoxic properties of Jbtx. GENERAL SIGNIFICANCE: Jbtx represents a new type of insecticidal and membrane-active peptide. PMID- 24239687 TI - Homologous Hevea brasiliensis REF (Hevb1) and SRPP (Hevb3) present different auto assembling. AB - HbREF and HbSRPP are two Hevea brasiliensis proteins present on rubber particles, and probably involved in the coagulation of latex. Their function is unclear, but we previously discovered that REF had amyloid properties, which could be of particular interest during the coagulation process. First, we confirmed that REF and SRPP, homologous and principal proteins in hevea latex, are not glycoproteins. In this work, we investigated various aspects of protein interactions: aggregation, auto-assembling, yeast and erythrocyte agglutination, co-interactions by various biochemical (PAGE, spectroscopy, microscopy), biophysical (DLS, ellipsometry) and structural (TEM, ATR-FTIR, PM-IRRAS) approaches. We demonstrated that both proteins are auto-assembling into different aggregative states: REF polymerizes as an amyloid rich in beta-sheets and forms quickly large aggregates (>MUm), whereas SRPP auto-assembles in solution into stable nanomultimers of a more globular nature. Both proteins are however able to interact together, and SRPP may inhibit the amyloidogenesis of REF. REF is also able to interact with the membranes of yeasts and erythrocytes, leading to their agglutination. In addition, we also showed that both REF and SRPP did not have antimicrobial activity, whereas their activity on membranes has been clearly evidenced. We may suspect that these aggregative properties, even though they are clearly different, may occur during coagulation, when the membrane is destabilized. The interaction of proteins with membranes could help in the colloidal stability of latex, whereas the protein-protein interactions would contribute to the coagulation process, by bringing rubber particles together or eventually disrupting the particle monomembranes. PMID- 24239688 TI - Abnormalities in whisking behaviour are associated with lesions in brain stem nuclei in a mouse model of amyotrophic lateral sclerosis. AB - The transgenic SOD1(G93A) mouse is a model of human amyotrophic lateral sclerosis (ALS) and recapitulates many of the pathological hallmarks observed in humans, including motor neuron degeneration in the brain and the spinal cord. In mice, neurodegeneration particularly impacts on the facial nuclei in the brainstem. Motor neurons innervating the whisker pad muscles originate in the facial nucleus of the brain stem, with contractions of these muscles giving rise to "whisking" one of the fastest movements performed by mammals. A longitudinal study was conducted on SOD1(G93A) mice and wild-type litter mate controls, comparing: (i) whisker movements using high-speed video recordings and automated whisker tracking, and (ii) facial nucleus degeneration using MRI. Results indicate that while whisking still occurs in SOD1(G93A) mice and is relatively resistant to neurodegeneration, there are significant disruptions to certain whisking behaviours, which correlate with facial nuclei lesions, and may be as a result of specific facial muscle degeneration. We propose that measures of mouse whisker movement could potentially be used in tandem with measures of limb dysfunction as biomarkers of disease onset and progression in ALS mice and offers a novel method for testing the efficacy of novel therapeutic compounds. PMID- 24239690 TI - Neurotransmissions of antidepressant-like effects of neuromedin U-23 in mice. AB - Neuromedin U (NmU) is a widely distributed and multifunctional peptide in the central nervous system and the peripheral tissues. Little is know about the mechanisms of NmU on brain functions. The rodent isoform of the NmU, NmU-23, has been shown to have anxiolytic effects involved in the beta-adrenergic and cholinergic nervous systems in elevated plus maze test. NmU-23 was tested for antidepressant-like effects in modified forced swimming test (FST) in mice and furthermore, the involvement of the adrenergic, serotonergic, cholinergic, dopaminergic or gaba-ergic receptors in the antidepressant-like effect of NmU-23 was studied in modified mice FST. Mice were pretreated with a non-selective alpha adrenergic receptor antagonist phenoxybenzamine, an alpha1/alpha2beta-adrenergic receptor antagonist, prazosin, an alpha2-adrenergic receptor antagonist, yohimbine, a beta-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5 HT2 serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, nonselective muscarinic acetylcholine receptor antagonist, atropine, D2,D3,D4 dopamine receptor antagonist, haloperidol or gamma-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline. NmU-23 showed the antidepressant-like effects by decreasing the immobility time and increasing the climbing and swimming time. Prazosin, haloperidol, and bicuculline prevented the effects of NmU-23 on the climbing and swimming time. Methysergide and cyproheptadine prevented the effects of NmU-23 on the immobility, swimming and climbing time. Atropine prevented the effects of NmU-23 on the climbing time. Phenoxybenzamine, yohimbine and propranolol did not change the effects of NmU-23. The results demonstrated that the antidepressant-like effect of NmU-23 is mediated, at least in part, by an interaction of the alpha2-adrenergic, 5-HT1-2 serotonergic, D2,D3,D4 dopamine receptor, muscarinic acetylcholine receptors and gamma-aminobutyric acid subunit A (GABAA) receptor in a modified mouse FST. PMID- 24239689 TI - Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure. AB - Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n=14) from healthy controls (n=12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD. PMID- 24239691 TI - Developmental alterations in locomotor and anxiety-like behavior as a function of D1 and D2 mRNA expression. AB - The majority of smokers start smoking in adolescence, beginning a potentially lifelong struggle with nicotine use and abuse. In rodent models of the effects of nicotine, the drug has been shown to elicit both locomotor and anxiety-like behavioral effects. Research suggests that these behavioral effects may be due in part to dopamine (DA) receptors D1 and D2 in the mesolimbic system, specifically the nucleus accumbens (NAc). We examined early adolescent (P28), late adolescent (P45), and adult (P80) male Long-Evans rats in the elevated plus maze (EPM) under normal conditions and the open field (OF) post-nicotine in order to test locomotor and anxiety-like behavior. These behavioral findings were then correlated with expression of DA D1 and D2 mRNA levels as determined via in situ hybridization. Nicotine-induced locomotor behavior was found to be significantly different between age groups. After a single injection of nicotine, early adolescents exhibited increases in locomotor behavior, whereas both late adolescents and adults responded with decreases in locomotor behavior. In addition, it was found that among, early adolescents, open arm and center time in the EPM were negatively correlated with D2 mRNA expression. In contrast, among adults, distance traveled in the center and center time in the OF were negatively correlated with D2 mRNA expression. This study suggests that DA D2 receptors play a role in anxiety-like behavior and that the relationship between observed anxiety-like behaviors and D2 receptor expression changes through the lifespan. PMID- 24239692 TI - Acute ethanol exposure induces behavioural differences in two zebrafish (Danio rerio) strains: a time course analysis. AB - The zebrafish has been proposed as a model organism to study genetic effects influencing behaviour and also as a tool with which the mechanisms of the action of alcohol (ethanol or EtOH) in the vertebrate brain may be investigated. In the current study we exposed zebrafish from two genetically distinct strains (WIK and TU) to a computer animated image of a natural predator of this species, the Indian leaf fish. We measured the subjects' behavioural responses in the presence of different acute doses of alcohol (0.00, 0.25, 0.50, and 1.00% vol/vol) using an observation based event-recording method. We found fish of both strains to exhibit an atypical predator inspection response during the presentation of the animated predator image coupled with a classical fear response, increased jumping frequency. We found numerous alcohol induced behavioural changes and more importantly also revealed alcohol induced strain dependent changes as well, including different dose-response trajectories for WIK vs. TU in predator inspection response, general swimming activity, location of swimming (top vs. bottom half of the tank) and freezing. The results suggest that zebrafish of the TU strain may be more tolerant at least to lower doses of alcohol as compared to WIK. The characterization of strain differences in zebrafish will aid the identification of possible molecular mechanisms involved in alcohol's actions in the vertebrate brain. PMID- 24239694 TI - Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury. AB - Traumatic brain injury (TBI) is characterized by neuronal damage and commonly, secondary cell death, leading to functional and neurological dysfunction. Despite the recent focus of TBI research on developing therapies, affective therapeutic strategies targeting neuronal death associated with TBI remain underexplored. This study explored the efficacy of granulocyte-colony stimulating factor (G-CSF) as an intervention for improving cognitive deficits commonly associated with TBI. Although G-CSF has been studied with histological techniques, to date, its effects on functional outcome remain unknown. To this end, we used a closed head injury (CHI) model in Wistar rats that were randomly assigned to one of four groups (untreated TBI, G-CSF treated TBI, G-CSF treated Control, Control). The treatment groups were administered subcutaneous injections of G-CSF 30 min (120 MUg/kg) and 12 h (60 MUg/kg) post-trauma. The Morris Water Maze test was used to measure any treatment-associated changes in cognitive deficits observed in TBI animals at days 2-6 post-injury. Our findings demonstrate a significant improvement in cognitive performance in the G-CSF treated TBI animals within a week of injury, compared to untreated TBI, indicative of immediate and beneficial effect of G-CSF on cognitive performance post CHI. Our model suggests that early G-CSF exposure may be a promising therapeutic approach in recovery of cognitive deficits due to TBI. PMID- 24239693 TI - Mesolimbic transcriptional response to hedonic substitution of voluntary exercise and voluntary ethanol consumption. AB - The mesolimbic dopaminergic pathway has been implicated in many rewarding behaviors, including the consumption of ethanol and voluntary exercise. It has become apparent that different rewarding stimuli activate this pathway, and therefore it is possible for these behaviors to influence each other, i.e. hedonic substitution. Using adult female C57BL/6J mice, we demonstrate that voluntary access to a running wheel substantially reduces the consumption and preference of ethanol. Furthermore, we examined gene expression of several genes involved in regulating the mesolimbic dopaminergic pathway, which we hypothesized to be the main pathway involved in hedonic substitution. In the striatum, we observed a reduction in mRNA expression of Drd1a due to exercise. Hippocampal Bdnf mRNA increased in response to exercise and decreased in response to ethanol. Furthermore, there was an interaction effect of exercise and ethanol on the expression of Slc18a2 in the midbrain. These data suggest an important role for this pathway, and especially for Bdnf and Slc18a2 in regulating hedonic substitution. PMID- 24239695 TI - Chronic nicotine attenuates phencyclidine-induced impulsivity in a mouse serial reaction time task. AB - Schizophrenia is a disorder characterized by positive, negative, and cognitive symptoms. While positive symptoms can be effectively treated with typical antipsychotic medication, which generally affects the dopaminergic system, negative and cognitive symptoms, including attentional deficits and impulsive behavior, are less sensitive to standard treatments. It has further been well documented that schizophrenic patients use tobacco products at a rate much higher than the general population, and this persists despite treatment. It has been argued this behavior may be a form of self-medication, to alleviate some symptoms of schizophrenia. It has further been posited that prefrontal glutamatergic hypofunction may underlie some aspects of schizophrenia, and in accordance with this model, systemic phencyclidine has been used to model the disease. We employed a modified 5-choice serial reaction time test, a paradigm that is often used to investigate many of the treatment-resistant symptoms of schizophrenia including impulsivity, selective attention, and sustained attention/cognitive vigilance, to determine the medicinal effects of nicotine. We demonstrate that chronic oral, but not acute injections of nicotine can selectively attenuate phencyclidine-induced increases in impulsivity without affecting other measures of attention. This suggests that nicotine use by schizophrenics may provide some relief of distinct symptoms that involve impulsive behaviors. PMID- 24239696 TI - The effect of brief neonatal cryoanesthesia on physical development and adult cognitive function in mice. AB - Deep hypothermia (cryoanesthesia) is often used as general anesthesia during surgery in neonatal rodents. Neonatal cryoanesthesia has been used recently to generate somatic brain transgenic (SBT) mouse models via intracerebral ventricular injection of rAAV vectors into both non-transgenic mice and numerous transgenic mouse models. Since, the evaluation of cognition is one of the main experimental endpoints in many of these studies, we examined the consequences of brief neonatal cryoanesthesia on the physical development and mnemonic function of adult mice. Two groups of 129FVBF1 pups from reciprocal breeding crosses underwent cryoanesthesia for 6 min (Cryo6) or 12 min (Cryo12), respectively, within the first hours (<12h) of postnatal life. A group of pups separated from the nest and kept in ambient temperature of 33 degrees C for 6 min served as a control. Our results revealed that lowering the temperature of pups to ~8 degrees C (Cryo6) or ~5 degrees C (Cryo12) did not affect their body weight at pre-weaning stage and in the adulthood. The evaluation of cognitive function in adult mice revealed strong and comparable to control spatial reference, and context and tone fear memories of neonatally cryoanesthetized mice. Also, the experimental and control groups had comparable brain weight at the end of the study. Our results demonstrate that neonatal cryoanesthesia, lasting up to 12 min, has no adverse effects on the body weight of mice during development, and on their cognition in the adulthood. PMID- 24239697 TI - Memory, learning, and participation of the cholinergic system in young rats exposed to environmental enrichment. AB - The present study demonstrates the consequences of animal exposure to an enriched environment compared to animals living in a standard environment regarding learning and space memory. Male albino Wistar rats were exposed to an enriched environment for 4 weeks after the lactation period and tested in the Morris water maze in the distal and proximal clue version and in the arena. In the former test, the animals were tested at 50 days of age with 12 daily trials on two consecutive days. At the end of each session, scopolamine at the dose of 0.6 mg/kg/ml or saline solution was injected intraperitoneally. Twenty-eight days after the first phase, a new test consisting of a single trial was held (retest). An independent group of animals receiving no drug was subjected to the arena test and to the proximal clue version of the Morris maze. In the distal clue version the results did not show differences between groups in the first phase of the experiment. After 28 days (retest), the animals reared in a standard environment and treated with scopolamine exhibited a significant increase in latency compared to the group receiving the same drug and stimulated and to the group receiving saline. The arena data demonstrated a significant increase in exploratory activity in the group of animals reared in an enriched environment. The proximal clue version of the Morris maze did not show differences between groups. The results of the present study indicate that animals exposed to environmental enrichment react less to the amnesic effects of scopolamine and show an increase in exploratory activity. PMID- 24239698 TI - Concentration dynamics and biodegradability of dissolved organic matter in wetland soils subjected to experimental warming. AB - Dissolved organic matter (DOM) is the most bioavailable soil organic pool. Understanding how DOM responds to elevated temperature is important for forecasting soil carbon (C) dynamics under climate warming. Here a 4.5-year field microcosm experiment was carried out to examine temporal DOM concentration dynamics in soil pore-water from six different subtropical wetlands. Results are compared between control (ambient temperature) and warmed (+5 degrees C) treatments. UV-visible and fluorescence spectroscopy was performed to reveal DOM structural complexity at the end of the warming incubation. Elevated temperature resulted in initially (1 to 2.5 years) high pore-water DOM concentrations in warmed samples. These effects gradually diminished over longer time periods. Of the spectral indices, specific UV absorbance at 280 nm and humification index were significantly higher, while the signal intensity ratio of the fulvic-like to humic-like fluorescence peak was lower in warmed samples, compared to the control. Fluorescence regional integration analysis further suggested that warming enhanced the contribution of humic-like substances to DOM composition for all tested wetlands. These spectral fingerprints implied a declined fraction of readily available substrates in DOM allocated to microbial utilization in response to 4.5 years of warming. As a negative feedback, decreased DOM biodegradability may have the potential to counteract initial DOM increases and alleviate C loss in water-saturated wetland soils. PMID- 24239699 TI - Molecular characterization of the PR-toxin gene cluster in Penicillium roqueforti and Penicillium chrysogenum: cross talk of secondary metabolite pathways. AB - The PR-toxin is a potent mycotoxin produced by Penicillium roqueforti in moulded grains and grass silages and may contaminate blue-veined cheese. The PR-toxin derives from the 15 carbon atoms sesquiterpene aristolochene formed by the aristolochene synthase (encoded by ari1). We have cloned and sequenced a four gene cluster that includes the ari1 gene from P. roqueforti. Gene silencing of each of the four genes (named prx1 to prx4) resulted in a reduction of 65-75% in the production of PR-toxin indicating that the four genes encode enzymes involved in PR-toxin biosynthesis. Interestingly the four silenced mutants overproduce large amounts of mycophenolic acid, an antitumor compound formed by an unrelated pathway suggesting a cross-talk of PR-toxin and mycophenolic acid production. An eleven gene cluster that includes the above mentioned four prx genes and a 14-TMS drug/H(+) antiporter was found in the genome of Penicillium chrysogenum. This eleven gene cluster has been reported to be very poorly expressed in a transcriptomic study of P. chrysogenum genes under conditions of penicillin production (strongly aerated cultures). We found that this apparently silent gene cluster is able to produce PR-toxin in P. chrysogenum under static culture conditions on hydrated rice medium. Noteworthily, the production of PR-toxin was 2.6-fold higher in P. chrysogenum npe10, a strain deleted in the 56.8kb amplifiable region containing the pen gene cluster, than in the parental strain Wisconsin 54-1255 providing another example of cross-talk between secondary metabolite pathways in this fungus. A detailed PR-toxin biosynthesis pathway is proposed based on all available evidence. PMID- 24239700 TI - Deletion of the putative stretch-activated ion channel Mid1 is hypervirulent in Aspergillus fumigatus. AB - Calcium ion is a universal and physiologically important molecule affecting almost every cellular function, while Mid1 (mating induced death) is a stretch activated ion channel localized in the plasma membrane, which can replenish the fungus with extracellular calcium. Aspergillus fumigatus is one of the most important fungal pathogens but little is known about its calcium channels in the plasma membrane. In this study, a homolog of Saccharomyces cerevisiae Mid1 was identified in A. fumigatus and its encoding gene afmid1 was deleted by replacing it with pyr4 selectable marker, designated as Deltaafmid1. Analysis of the phenotypes demonstrated that Deltaafmid1 had growth defects under solid and liquid cultural conditions. The mutant Deltaafmid1 had delayed germination in minimal medium and abnormal morphogenesis in the medium containing ethylene glycol tetraacetic acid (EGTA), an agent with major affinity for Ca(2+) and minor affinity for Mn(2+). The sensitivity against cell wall disturbing agents, osmotic stress, alkaline environments, high temperatures or starvation in Deltaafmid1 resembled wild type. However, the mutant Deltaafmid1 demonstrated more sensitivity to oxidative agents (H2O2 and Menadione) than wild type. Most surprisingly, deletion of afmid1 from A. fumigatus led to hypervirulence in the immunosuppressed mice model. PMID- 24239702 TI - The impact of neighborhood walkability on walking: does it differ across adult life stage and does neighborhood buffer size matter? AB - We explored the impact of neighborhood walkability on young adults, early-middle adults, middle-aged adults, and older adults' walking across different neighborhood buffers. Participants completed the Western Australian Health and Wellbeing Surveillance System Survey (2003-2009) and were allocated a neighborhood walkability score at 200m, 400m, 800m, and 1600m around their home. We found little difference in strength of associations across neighborhood size buffers for all life stages. We conclude that neighborhood walkability supports more walking regardless of adult life stage and is relevant for small (e.g., 200m) and larger (e.g., 1600m) neighborhood buffers. PMID- 24239701 TI - Low-field MRI can be more sensitive than high-field MRI. AB - MRI signal-to-noise ratio (SNR) is the key factor for image quality. Conventionally, SNR is proportional to nuclear spin polarization, which scales linearly with magnetic field strength. Yet ever-stronger magnets present numerous technical and financial limitations. Low-field MRI can mitigate these constraints with equivalent SNR from non-equilibrium 'hyperpolarization' schemes, which increase polarization by orders of magnitude independently of the magnetic field. Here, theory and experimental validation demonstrate that combination of field independent polarization (e.g. hyperpolarization) with frequency optimized MRI detection coils (i.e. multi-turn coils using the maximum allowed conductor length) results in low-field MRI sensitivity approaching and even rivaling that of high-field MRI. Four read-out frequencies were tested using samples with identical numbers of (1)H and (13)C spins. Experimental SNRs at 0.0475T were ~40% of those obtained at 4.7T. Conservatively, theoretical SNRs at 0.0475T 1.13-fold higher than those at 4.7T were possible despite an ~100-fold lower detection frequency, indicating feasibility of high-sensitivity MRI without technically challenging, expensive high-field magnets. The data at 4.7T and 0.0475T was obtained from different spectrometers with different RF probes. The SNR comparison between the two field strengths accounted for many differences in parameters such as system noise figures and variations in the probe detection coils including Q factors and coil diameters. PMID- 24239703 TI - Perception and trends of associated health risks with seasonal climate variation in Oke-Ogun region, Nigeria. AB - This paper investigates the perceived and observed trends of associated health risks with seasonal climate variability and identifies types of and preference for adaptation strategies that are available at households and community levels in Oke-Ogun region, Nigeria. The study made use of household survey and rapid appraisal through focus group discussion and key informant interviews. For a short term climate-health impacts analysis, cases of notable diseases were correlated with monthly mean temperature and rainfall for the period 2006 and 2008. The findings show similar trends in relation to local perception on climate health risks and observed cases of some notable diseases during seasonal changes. Diarrhea, measles and malaria were prevalent during dry season, while flu cases increased at the onset of harmattan and monsoon of rainy season. Available adaptation strategies are autonomous, mostly in the form of treatment measures such as consultation with medical officers in hospitals (17.5%), self-medication (34%) and use of traditional therapy such as herbs (48.5%). Traditional therapy is mostly preferred and approved based on long-term experience of the study population. PMID- 24239704 TI - Deficiency of protease-activated receptor-1 limits bacterial dissemination during severe Gram-negative sepsis (melioidosis). AB - Protease-activated receptor-1 (PAR-1) is a G-coupled transmembrane receptor expressed by multiple cell types present in the lungs that can be activated by various proteases generated during acute inflammation. In this study we aimed to investigate the role of PAR-1 during melioidosis, a common cause of (pneumo)sepsis in Southeast Asia in a murine model of intranasal inoculation of the causative pathogen Burkholderia (B.) pseudomallei. Our results show that endogenous PAR-1 facilitates bacterial growth and dissemination during murine melioidosis, which is associated with increased cell influxes. However, these observations have no impact on survival. PMID- 24239705 TI - Surgical safety checklists in developing countries. AB - The World Health Organization Surgical Safety Checklist (WHO SSC) has demonstrated efficacy in developed and developing countries alike. Recent increases in awareness of surgical morbidity in developing countries has placed greater emphasis on strategies to improve surgical safety in resource-limited settings. The implementation of surgical safety checklists in low-income countries has specific barriers related to resources and culture. Adapting and amending existing surgical safety checklists, as well as considering factors unique to developing countries, may allow the potential of this simple intervention to be fully harnessed in a wider setting. This review will address the benefits and challenges of implementation of surgical safety checklists in developing countries. Moreover, inspiration for the original checklist is revisited to identify areas that will be of particular benefit in a resource-poor setting. Potential future strategies to encourage the implementation of checklists in these countries are also discussed. PMID- 24239706 TI - The broadening spectrum of mitochondrial disease: shifts in the diagnostic paradigm. AB - BACKGROUND: The diagnosis of mitochondrial disease requires a complex synthesis of clinical, biochemical, histological, and genetic investigations. An expanding number of mitochondrial diseases are being recognized, despite their phenotypic diversity, largely due to improvements in methods to detect mutations in affected individuals and the discovery of genes contributing to mitochondrial function. Improved understanding of the investigational pitfalls and the development of new laboratory methodologies that lead to a molecular diagnosis have necessitated the field to rapidly adopt changes to its diagnostic approach. SCOPE OF REVIEW: We review the clinical, investigational and genetic challenges that have resulted in shifts to the way we define and diagnose mitochondrial disease. Incorporation of changes, including the use of fibroblast growth factor 21 (FGF-21) and next generation sequencing techniques, may allow affected patients access to earlier molecular diagnosis and management. MAJOR CONCLUSIONS: There have been important shifts in the diagnostic paradigm for mitochondrial disease. Diagnosis of mitochondrial disease is no longer reliant on muscle biopsy alone, but should include clinical assessment accompanied by the use of serological biomarkers and genetic analysis. Because affected patients will be defined on a molecular basis, oligosymptomatic mutation carriers should be included in the spectrum of mitochondrial disease. Use of new techniques such as the measurement of serum FGF 21 levels and next-generation-sequencing protocols should simplify the diagnosis of mitochondrial disease. GENERAL SIGNIFICANCE: Improvements in the diagnostic pathway for mitochondrial disease will result in earlier, cheaper and more accurate methods to identify patients with mitochondrial disease. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. PMID- 24239707 TI - Variation in moisture duration as a driver of coexistence by the storage effect in desert annual plants. AB - Temporal environmental variation is a leading hypothesis for the coexistence of desert annual plants. Environmental variation is hypothesized to cause species specific patterns of variation in germination, which then generates the storage effect coexistence mechanism. However, it has never been shown how sufficient species differences in germination patterns for multispecies coexistence can arise from a shared fluctuating environment. Here we show that nonlinear germination responses to a single fluctuating physical environmental factor can lead to sufficient differences between species in germination pattern for the storage effect to yield coexistence of multiple species. We derive these nonlinear germination responses from experimental data on the effects of varying soil moisture duration. Although these nonlinearities lead to strong species asymmetries in germination patterns, the relative nonlinearity coexistence mechanism is minor compared with the storage effect. However, these asymmetries mean that the storage effect can be negative for some species, which then only persist in the face of interspecific competition through average fitness advantages. This work shows how a low dimensional physical environment can nevertheless stabilize multispecies coexistence when the species have different nonlinear responses to common conditions, as supported by our experimental data. PMID- 24239708 TI - IFN-gamma in turtle: conservation in sequence and signalling and role in inhibiting iridovirus replication in Chinese soft-shelled turtle Pelodiscus sinensis. AB - The IFN-gamma gene was identified in a turtle, the Chinese soft-shelled turtle, Pelodiscus sinensis, with its genome consisting of 4 exons and 3 introns. The deduced amino acid sequence of this gene contains a signal peptide, an IFN-gamma family signature motif (130)IQRKAVNELFPT, an NLS motif (155)KRKR and three potential N-glycosylation sites. As revealed by real-time quantitative PCR, the gene was constitutively expressed in all tested organs/tissues, with higher level observed in blood, intestine and thymus. An induced expression of IFN-gamma at mRNA level was observed in peripheral blood leucocytes (PBLs) in response to in vitro stimulation of LPS and PolyI:C. The overexpression of IFN-gamma in the Chinese soft-shelled turtle artery (STA) cell line resulted in the increase in the expression of transcriptional regulators, such as IRF1, IRF7 and STAT1, and antiviral genes, such as Mx, PKR, implying possibly the existence of a conserved signalling network and role for IFN-gamma in the turtle. Furthermore, the infection of soft-shelled turtle iridovirus (STIV) in the cell line transfected with IFN-gamma may cause the cell death as demonstrated with the elevated lactate dehydrogenase (LDH) level and cell mortality. However, the mechanism involved in the antiviral activity may require further investigation. PMID- 24239709 TI - Expression of antimicrobial peptides in coelomocytes and embryos of the green sea urchin (Strongylocentrotus droebachiensis). AB - Antimicrobial peptides (AMPs) play a crucial role in innate immunity. We have previously reported the isolation and characterization of the AMPs, strongylocins 1 and 2, and centrocin 1, from coelomocyte extracts of Strongylocentrotus droebachiensis. Here we show that these AMPs were expressed in phagocytes. In addition, transcripts of strongylocin 1 were detected in vibratile cells and/or colorless spherule cells, while transcripts of strongylocin 2 were found in red spherule cells. Results from immunoblotting and immunocytochemistry studies showed that centrocin 1 was produced by phagocytes and stored in granular vesicles. Co-localization of centrocin 1 and phagocytosed bacteria suggests that the granular vesicles containing centrocin 1 may be involved in the formation of phagolysosomes. We also analyzed the temporal and spatial expression of AMPs throughout larval development. Strongylocins were expressed in the early pluteus stage, while centrocin 1 was expressed in the mid pluteus stage. The spatial expression pattern showed that centrocin 1 was mainly located in blastocoelar cells (BCs) around the stomach and the esophagus. In addition, a few patrolling BCs were detected in some larval arms. Together, these results suggest that AMPs are expressed in different types of coelomocytes and that centrocin 1 is involved in response against bacteria. Furthermore, the expression of AMPs in larval pluteus stage, especially in BCs, indicates that AMPs and BCs are engaged in the larval immune system. PMID- 24239710 TI - Fluorescence spectroscopy of Rhodamine 6G: concentration and solvent effects. AB - Rhodamine 6G (R6G), also known as Rhodamine 590, is one of the most frequently used dyes for application in dye lasers and as a fluorescence tracer, e.g., in the area of environmental hydraulics. Knowing the spectroscopic characteristics of the optical emission is key to obtaining high conversion efficiency and measurement accuracy, respectively. In this work, solvent and concentration effects are studied. A series of eight different organic solvents (methanol, ethanol, n-propanol, iso-propanol, n-butanol, n-pentanol, acetone, and dimethyl sulfoxide (DMSO)) are investigated at constant dye concentration. Relatively small changes of the fluorescence spectrum are observed for the different solvents; the highest fluorescence intensity is observed for methanol and lowest for DMSO. The shortest peak wavelength is found in methanol (568 nm) and the longest in DMSO (579 nm). Concentration effects in aqueous R6G solutions are studied over the full concentration range from the solubility limit to highly dilute states. Changing the dye concentration provides tunability between ~550 nm in the dilute case and ~620 nm at high concentration, at which point the fluorescence spectrum indicates the formation of R6G aggregates. PMID- 24239711 TI - A study of the interaction tyrosine and DNA using voltammetry and spectroscopy methods. AB - The interaction of tyrosine (Tyr) with double stranded DNA was studied by cyclic voltammetry, fluorescence emission spectroscopy, and UV-vis spectroscopy. The presence of DNA on a single-walled carbon nanotubes (DNA/SWCNT/GCE) and multi walled carbon nanotubes (DNA/MWCNT/GCE) modified glassy carbon electrode showed a decrease in the current and a positive shift in the Tyr oxidation peak, indicating the intercalative interaction. The transfer coefficient (alpha), heterogeneous rate constant (k(s)), and surface concentration (Gamma) were calculated in the absence and presence of DNA. The corresponding binding constant of Tyr with DNA and Hill coefficient were obtained from cooperative Hill model. The UV spectroscopic data confirmed the interaction between Tyr and DNA is intercalative with the binding constant of 3.98*10(3) mol(-1) L. Furthermore, the mechanism of fluorescence quenching has been discussed and the binding constant and numbers of binding sites were obtained as 3.37*10(3) mol(-1) L and 2, respectively from the Stern-Volmer plot. PMID- 24239712 TI - Depression, C-reactive protein and length of post-operative hospital stay in coronary artery bypass graft surgery patients. AB - This study aimed to explore the role of C-reactive protein (CRP) in mediating the association between greater pre-operative depression symptoms and longer post operative length of stay in patients undergoing coronary artery bypass graft (CABG) surgery. We used a sample of 145 elective CABG patients and measured depression symptoms using the Beck Depression Inventory (BDI) prior to surgery and collected baseline measures of CRP. Participants were followed up during their in-hospital stay to measure early (1-3 days post-surgery) and persistent (4 8 days post-surgery) CRP responses to surgery. We found that compared with participants with low depression symptoms, those with elevated depression symptoms (BDI>10) prior to CABG were at increased odds of a hospital stay of greater than one week (OR 3.51, 95% CI 1.415-8.693, p=0.007) and that greater persistent CRP responses mediated this association. Further work is needed to explore the exact physiological pathways through which depression and CRP interact to affect recovery in CABG patients. PMID- 24239713 TI - Emodin attenuates A23187-induced mast cell degranulation and tumor necrosis factor-alpha secretion through protein kinase C and IkappaB kinase 2 signaling. AB - Mast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity IgE receptor (FcepsilonRI) is known to be one of the major causes that lead to degranulation and allergic inflammation. An increase in intracellular calcium (Ca(2+)) concentration also triggers degranulation, bypassing receptor activation. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is known to exhibit a variety of pharmacological activities including anti-allergic effects. However, the detailed molecular mechanisms involved in exhibiting anti allergic effects by emodin were remained to be clarified. In the present investigation we report the regulatory function of emodin on the allergic signal mediators through Ca(2+) ionophore activation in mast cells. Emodin significantly inhibited A23187-induced tumor necrosis factor-alpha production and degranulation through the attenuation of protein kinase C, IkappaB kinase 2, and soluble N ethylmaleimide-sensitive fusion factor attachment protein receptor complex formation, bypassing FcepsilonRI activation. Data from our study indicated that emodin acts by regulating multiple signaling pathways in inhibiting the allergic reactions in mast cells. PMID- 24239714 TI - Inhibitory effects of quercetin on angiogenesis in larval zebrafish and human umbilical vein endothelial cells. AB - Angiogenesis plays an essential role in many physiological and pathological processes. Quercetin, a plant pigment and traditional Chinese medicinal herb, is an important flavonoid that has anti-cancer activity. However, the function of quercetin in blood vessel development in vivo and in vitro is still unclear. In this study, we investigated the anti-angiogenic activity of quercetin in zebrafish embryos and in human umbilical vein endothelial cells (HUVECs). Our results showed that quercetin disrupted the formation of intersegmental vessels, the dorsal aorta and the posterior cardinal vein in transgenic zebrafish embryos. In HUVECs, quercetin inhibited cell viability, the expression of vascular endothelial growth factor receptor 2 and tube formation in a dose-dependent manner. In inhibiting angiogenesis, quercetin was found to be involved in suppressing the extracellular signal-regulated kinase signaling pathway in vivo and in vitro. This study has shown that quercetin has potent anti-angiogenic activity and may be a candidate anti-cancer agent for future research. PMID- 24239715 TI - Anti-proliferative effect of recombinant human endostatin on synovial fibroblasts in rats with adjuvant arthritis. AB - Rheumatoid arthritis (RA) is characterized by pronounced synovial hyperplasia resulting in pannus formation, cartilage erosion and ultimately joint destruction. Activated RA synovial fibroblasts (SFs) mediate the invasion and destruction of cartilage and bone. We previously demonstrated that recombinant human endostatin (rhEndostatin) is sufficient to induce SF apoptosis in adjuvant arthritis (AA) rats. However, the effect of this protein on SF proliferation is unknown. This study was designed to assess the inhibitory effect and mechanisms of rhEndostatin on the proliferation of cultured AA SFs. MTT assay and flow cytometric detection were performed to investigate SF proliferation and cell cycle progression, respectively. Also, the expression levels of p53, p21, cyclin D1, CDK4 and PCNA in AA SFs were detected by real-time PCR and western blotting assays. Our data revealed that AA SF proliferation was significantly inhibited by rhEndostatin in a concentration-dependent manner. In addition, rhEndostatin (50MUg/ml) caused the G0/G1 cell cycle arrest of AA SFs. There were significant decreases in the expression levels of p53, p21, cyclin D1 and PCNA in AA SFs treated with rhEndostatin, and a significant increase in CDK4 expression. Collectively, our data suggest that rhEndostatin inhibits AA SF proliferation, which is preceded by cell cycle arrest at the G0/G1 phase. This is partly due to the inhibitory effect of rhEndostatin on cyclin D1 and PCNA by a p53-p21-CDK4 independent mechanism. Taken together, these findings highlight the potential use of rhEndostatin for RA treatment. PMID- 24239716 TI - Medial prefrontal cortex inactivation attenuates the diurnal rhythm in amphetamine reward. AB - Psychostimulant reward, as assessed via the conditioned place preference (CPP) paradigm, exhibits a daily rhythm with peaks in the late dark and early light periods, and a nadir near the light-to-dark transition. While this diurnal rhythm is correlated with neural activity in several corticolimbic structures, the brain regions mediating this behavioral rhythm remain unknown. Here, we examine the role of the ventral medial prefrontal cortex (mPFC). The effects of excitotoxic mPFC lesions on daily rhythms in amphetamine CPP were examined at previously observed peak (zeitgeber time [ZT] 23) and nadir times (ZT11). mPFC lesions encompassing the prelimbic and infralimbic subregions increased the CPP for amphetamine at the nadir time, thereby eliminating the daily rhythm in amphetamine reward. To examine the effects of transient mPFC inactivation, rats received intra-mPFC infusions of GABA receptor agonists during the acquisition or expression phases of CPP testing. Inactivation of the ventral mPFC at either of these phases also eliminated the daily rhythm in amphetamine-induced CPP via an increase in drug-paired chamber dwell time at the baseline nadir. Together, these results indicate that the ventral mPFC plays a critical role in mediating the diurnal rhythm in amphetamine CPP during both the acquisition and expression of learned reward-context associations. Moreover, as the loss of rhythmicity occurs via an increase at the nadir point, these results suggest that excitatory output from the ventral mPFC normally inhibits context-elicited reward seeking prior to the light-to-dark transition. PMID- 24239718 TI - Sensory transduction of weak electromagnetic fields: role of glutamate neurotransmission mediated by NMDA receptors. AB - Subliminal electromagnetic fields (EMFs) triggered nonlinear evoked potentials in awake but not anesthetized animals, and increased glucose metabolism in the hindbrain. Field detection occurred somewhere in the head and possibly was an unrecognized function of sensory neurons in facial skin, which synapse in the trigeminal nucleus and project to the thalamus via glutamate-dependent pathways. If so, anesthetic agents that antagonize glutamate neurotransmission would be expected to degrade EMF-evoked potentials (EEPs) to a greater extent than agents having different pharmacological effects. We tested the hypothesis using ketamine which blocks N-methyl-d-aspartate (NMDA) receptors (NMDARs), and xylazine which is an alpha2-adrenoreceptor agonist. Electroencephalograms (EEGs) of rats were examined using recurrence analysis to observe EEPs in the presence and absence of ketamine and/or xylazine anesthesia. Auditory evoked potentials (AEPs) served as positive controls. The frequency of observation of evoked potentials in a given condition (wake or anesthesia) was compared with that due to chance using the Fisher's exact test. EEPs were observed in awake rats but not while they were under anesthesia produced using a cocktail of xylazine and ketamine. In another experiment each rat was measured while awake and while under anesthesia produced using either xylazine or ketamine. EEPs and AEPs were detected during wake and under xylazine (P<0.05 in each of the four measurements). In contrast, neither EEPs nor AEPs were observed when anesthesia was produced partly or wholly using ketamine. The duration and latency of the EEPs was unaltered by xylazine anesthesia. The afferent signal triggered by the transduction of weak EMFs was likely mediated by NMDAR-mediated glutamate neurotransmission. PMID- 24239717 TI - Ectopic endometrium-derived leptin produces estrogen-dependent chronic pain in a rat model of endometriosis. AB - Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. Rats implanted with autologous uterine tissue onto the gastrocnemius muscle developed endometriosis-like lesions and local chronic pain. Compared to eutopic uterine tissue, leptin mRNA and protein were up-regulated in the endometriosis like lesions. Intramuscular injection of recombinant leptin in naive rats produced dose-dependent local mechanical hyperalgesia and nociceptor sensitization to mechanical stimulation. Ovariectomy attenuated the mechanical hyperalgesia induced by recombinant leptin, in rats treated with vehicle compared to those treated with 17beta-estradiol replacement, at 1 and 24 h after leptin injection. Finally, intralesional injections of a pegylated leptin receptor (Ob R) antagonist or of an inhibitor of Janus kinase2, which transduces the Ob-R signal, markedly attenuated pain in the endometriosis model. Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain. PMID- 24239719 TI - Intimate associations between the endogenous opiate systems and the growth hormone-releasing hormone system in the human hypothalamus. AB - Although it is a general consensus that opioids modulate growth, the mechanism of this phenomenon is largely unknown. Since endogenous opiates use the same receptor family as morphine, these peptides may be one of the key regulators of growth in humans by impacting growth hormone (GH) secretion, either directly, or indirectly, via growth hormone-releasing hormone (GHRH) release. However, the exact mechanism of this regulation has not been elucidated yet. In the present study we identified close juxtapositions between the enkephalinergic/endorphinergic/dynorphinergic axonal varicosities and GHRH immunoreactive (IR) perikarya in the human hypothalamus. Due to the long post mortem period electron microscopy could not be utilized to detect the presence of synapses between the enkephalinergic/endorphinergic/dynorphinergic and GHRH neurons. Therefore, we used light microscopic double-label immunocytochemistry to identify putative juxtapositions between these systems. Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with enkephalinergic axonal varicosities in the infundibular nucleus/median eminence, while endorphinergic-GHRH juxtapositions were much less frequent. In contrast, no significant dynorphinergic-GHRH associations were detected. The density of the abutting enkephalinergic fibers on the surface of the GHRH perikarya suggests that these juxtapositions may be functional synapses and may represent the morphological substrate of the impact of enkephalin on growth. The small number of GHRH neurons innervated by the endorphin and dynorphin systems indicates significant differences between the regulatory roles of endogenous opiates on growth in humans. PMID- 24239721 TI - Calcium signaling and the MAPK cascade are required for sperm activation in Caenorhabditis elegans. AB - In nematode, sperm activation (or spermiogenesis), a process in which the symmetric and non-motile spermatids transform into polarized and crawling spermatozoa, is critical for sperm cells to acquire fertilizing competence. SPE-8 dependent and SPE-8 independent pathways function redundantly during sperm activation in both males and hermaphrodites of Caenorhabditis elegans. However, the downstream signaling for both pathways remains unclear. Here we show that calcium signaling and the MAPK cascade are required for both SPE-8 dependent and SPE-8 independent sperm activation, implying that both pathways share common downstream signaling components during sperm activation. We demonstrate that activation of the MAPK cascade is sufficient to activate spermatids derived from either wild-type or spe-8 group mutant males and that activation of the MAPK cascade bypasses the requirement of calcium signal to induce sperm activation, indicating that the MAPK cascade functions downstream of or parallel with the calcium signaling during sperm activation. Interestingly, the persistent activation of MAPK in activated spermatozoa inhibits Major Sperm Protein (MSP) based cytoskeleton dynamics. We demonstrate that MAPK plays dual roles in promoting pseudopod extension during sperm activation but also blocking the MSP based, amoeboid motility of the spermatozoa. Thus, though nematode sperm are crawling cells, morphologically distinct from flagellated sperm, and the molecular machinery for motility of amoeboid and flagellated sperm is different, both types of sperm might utilize conserved signaling pathways to modulate sperm maturation. PMID- 24239720 TI - Epigenetic mechanisms in pubertal brain maturation. AB - Puberty is a critical period of development during which the reemergence of gonadotropin-releasing hormone secretion from the hypothalamus triggers a cascade of hormone-dependent processes. Maturation of specific brain regions including the prefrontal cortex occurs during this window, but the complex mechanisms underlying these dynamic changes are not well understood. Particularly, the potential involvement of epigenetics in this programming has been under-examined. The epigenome is known to guide earlier stages of development, and it is similarly poised to regulate vital pubertal-driven brain maturation. Further, as epigenetic machinery is highly environmentally responsive, its involvement may also lend this period of growth to greater vulnerability to external insults, resulting in reprogramming and increased disease risk. Importantly, neuropsychiatric diseases commonly present in individuals during or immediately following puberty, and environmental perturbations including stress may precipitate disease onset by disrupting the normal trajectory of pubertal brain development via epigenetic mechanisms. In this review, we discuss epigenetic processes involved in pubertal brain maturation, the potential points of derailment, and the importance of future studies for understanding this dynamic developmental window and gaining a better understanding of neuropsychiatric disease risk. PMID- 24239722 TI - Isoforms of protein kinase C involved in phorbol ester-induced sphingosine 1 phosphate receptor 1 phosphorylation and desensitization. AB - The role of protein kinase C (PKC) isozymes in phorbol myristate acetate (PMA) induced sphingosine 1-phosphate (S1P) receptor 1 (S1P1) phosphorylation was studied. Activation of S1P1 receptors induced an immediate increase in intracellular calcium, which was blocked by preincubation with PMA. Both S1P and PMA were able to increase S1P1 phosphorylation in a concentration- and time dependent fashion. Down-regulation of PKC (overnight incubation with PMA) blocked the subsequent effect of the phorbol ester on S1P1 phosphorylation, without decreasing that of the natural agonist. Pharmacological inhibition of PKC alpha prevented the effects of PMA on S1P-triggered intracellular calcium increase and on S1P1 phosphorylation; no such effect was observed on the effects of the sphingolipid agonist. The presence of PKC alpha and beta isoforms in S1P1 immunoprecipitates was evidenced by Western blotting. Additionally, expression of dominant-negative mutants of PKC alpha or beta and knockdown of these isozymes using short hairpin RNA, markedly attenuated PMA-induced S1P1 phosphorylation. Our results indicate that the classical isoforms, mainly PKC alpha, mediate PMA induced phosphorylation and desensitization of S1P1. PMID- 24239723 TI - Ascorbic acid suppresses endotoxemia and NF-kappaB signaling cascade in alcoholic liver fibrosis in guinea pigs: a mechanistic approach. AB - Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-kappaB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4g/kg b.wt for 90days. After 90days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250mg/kg b.wt) and AA (250mg/kg b.wt) supplemented groups and maintained for 30days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKbeta and the protein expressions of phospho IkappaBalpha, NF-kappaB, TNF-alpha, TGF-beta1 and IL-6 were also altered in ethanol group. The expressions of fibrosis markers alpha-SMA, alpha1 (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-kappaB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKbeta, which decreased the activation of NF kappaB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis. PMID- 24239725 TI - Towards the realisation of lead-oriented synthesis. AB - Sourcing large numbers of lead-like molecules - compounds that would serve as good starting points for drug discovery programmes - is currently very challenging. The concept of lead-oriented synthesis has recently been articulated to capture the specific problem of preparing diverse small molecules with lead like molecular properties. In this Feature, some methods that might be used to prepare lead-like molecular scaffolds are described, and presented in the context of diversity-oriented synthetic strategies that allow wide variation in molecular scaffold. It is concluded that the development of a wider toolkit of reactions that is reliable with more polar substrates will be required to allow genuine combination of molecular scaffold within lead-like chemical space. PMID- 24239724 TI - Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms. AB - To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969MUg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too. PMID- 24239726 TI - Drug-eluting scaffolds for bone and cartilage regeneration. AB - The advances in strategies for bone and cartilage regeneration have been centered on a concept that describes the close relationship between osteogenic cells, osteoconductive scaffolds, delivery growth factors and the mechanical environment. The dynamic nature of the tissue repair process involves intricate mimicry of signals expressed in the biological system in response to an injury. Recently, synergistic strategies involving hybrid delivery systems that provide sequential dual delivery of biomolecules and relevant topological cues received great attention. Future advances in tissue regeneration will therefore depend on multidisciplinary strategies that encompass the crux of tissue repair aimed at constructing the ideal functional regenerative scaffold. Here, functional scaffolds delivering therapeutics are reviewed in terms of their controlled release and healing capabilities. PMID- 24239727 TI - Antibody-drug conjugates: current status and future directions. AB - Antibody-drug conjugates (ADCs) aim to take advantage of the specificity of monoclonal antibodies (mAbs) to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells. Despite the simple concept, various parameters must be considered when designing optimal ADCs, such as selection of the appropriate antigen target and conjugation method. Each component of the ADC (the antibody, linker and drug) must also be optimized to fully realize the goal of a targeted therapy with improved efficacy and tolerability. Advancements over the past several decades have led to a new generation of ADCs comprising non immunogenic mAbs, linkers with balanced stability and highly potent cytotoxic agents. Although challenges remain, recent clinical success has generated intense interest in this therapeutic class. PMID- 24239729 TI - Development of predictive genetic tests for improving the safety of new medicines: the utilization of routinely collected electronic health records. AB - Serious adverse drug reactions are an important cause of hospitalization and can result in the withdrawal of licensed drugs. Genetic variation has been shown to influence adverse drug reaction susceptibility, and predictive genetic tests have been developed for a limited number of adverse drug reactions. The identification of patients with adverse drug reactions, obtaining samples for genetic analysis and rigorous evaluation of clinical test effectiveness represent significant challenges to predictive genetic test development. Using the example of serious drug-induced liver injury, we illustrate how a database of routinely collected electronic health records (EHRs) could be used to overcome these barriers by facilitating rapid recruitment to genome-wide association studies and supporting efficient randomized controlled trials of predictive genetic test effectiveness. PMID- 24239728 TI - Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. AB - Recycling old drugs, rescuing shelved drugs and extending patents' lives make drug repositioning an attractive form of drug discovery. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA) approved drugs and vaccines in recent years. The prevalence of drug-repositioning studies has resulted in a variety of innovative computational methods for the identification of new opportunities for the use of old drugs. Questions often arise from customizing or optimizing these methods into efficient drug repositioning pipelines for alternative applications. It requires a comprehensive understanding of the available methods gained by evaluating both biological and pharmaceutical knowledge and the elucidated mechanism-of-action of drugs. Here, we provide guidance for prioritizing and integrating drug-repositioning methods for specific drug-repositioning pipelines. PMID- 24239730 TI - Obituary: Homo phykophilos--Dieter Mollenhauer, December 29, 1937-May 3, 2013. PMID- 24239731 TI - A short guide to common heterotrophic flagellates of freshwater habitats based on the morphology of living organisms. PMID- 24239732 TI - The facial motor system. AB - Facial movements support a variety of functions in human behavior. They participate in automatic somatic and visceral motor programs, they are essential in producing communicative displays of affective states and they are also subject to voluntary control. The multiplicity of functions of facial muscles, compared to limb muscles, is reflected in the heterogeneity of their anatomical and histological characteristics that goes well beyond the conventional classification in single facial muscles. Such parcellation in different functional muscular units is maintained throughout the central representation of facial movements from the brainstem up to the neocortex. Facial movements peculiarly lack a conventional proprioceptive feedback system, which is only in part vicariated by cutaneous or auditory afferents. Facial motor activity is the main marker of endogenous affective states and of the affective valence of external stimuli. At the cortical level, a complex network of specialized motor areas supports voluntary facial movements and, differently from upper limb movements, in such network there does not seem to be a prime actor in the primary motor cortex. PMID- 24239734 TI - The effects of noise over the complete space of diffusion tensor shape. AB - Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique used to quantify the microstructural organization of biological tissues. Multiple images are necessary to reconstruct the tensor data and each acquisition is subject to complex thermal noise. As such, measures of tensor invariants, which characterize components of tensor shape, derived from the tensor data will be biased from their true values. Previous work has examined this bias, but over a narrow range of tensor shape. Herein, we define the mathematics for constructing a tensor from tensor invariants, which permits an intuitive and principled means for building tensors with a complete range of tensor shape and salient microstructural properties. Thereafter, we use this development to evaluate by simulation the effects of noise on characterizing tensor shape over the complete space of tensor shape for three encoding schemes with different SNR and gradient directions. We also define a new framework for determining the distribution of the true values of tensor invariants given their measures, which provides guidance about the confidence the observer should have in the measures. Finally, we present the statistics of tensor invariant estimates over the complete space of tensor shape to demonstrate how the noise sensitivity of tensor invariants varies across the space of tensor shape as well as how the imaging protocol impacts measures of tensor invariants. PMID- 24239733 TI - Depression and impulse control disorders in Parkinson's disease: two sides of the same coin? AB - Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seem associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT). Not all DRT using PD patients, however, develop symptoms of ICD, suggesting an additional underlying neurobiological susceptibility. Furthermore, the symptoms of depression and ICD frequently coincide even though they are related to seemingly contrasting limbic CSTC circuit activation states. The aim of this review is to provide an overview of the currently available literature on the neurobiology of PD-related depression and ICD and discusses possible susceptibility factors. Finally, we propose a neurobiological model that identifies ventral striatal dopaminergic denervation as a common underlying neurobiological substrate of depression and ICD and subsequent dysfunction of reward and motivation-related brain areas. PMID- 24239735 TI - Practice trends in the utilization of intraoperative neurophysiological monitoring in pediatric neurosurgery as a function of complication rate, and patient-, surgeon-, and procedure-related factors. AB - OBJECTIVE: Higher benchmarks in safety for patients undergoing neurosurgery have been introduced. With these principles, new tools and techniques were established, including intraoperative neurophysiological monitoring (IONM). Current trends as a function of patient-, surgeon-, and procedure-related factors and complication rates in the utilization of IONM as an adjunct to the practice of pediatric neurosurgery have not been investigated previously. METHODS: Between 2008 and 2011, 4467 neurosurgical procedures were performed on 2352 patients at Texas Children's Hospital. A retrospective chart review was performed in which surgeon, procedure, and patient characteristics, as well as perioperative complications, were recorded for IONM and non-IONM cases. RESULTS: Neurosurgical procedures performed with IONM steadily increased. Surgeon-related factors associated with IONM use included surgeons with <10 years of practice (P < .0001), and subspecialty interest in spine (P < .0001) and oncology (P = .0048). Procedure-related factors associated with IONM use included operations involving the spinal cord (P < .0001). Patient-related factors associated with IONM use included children older than 3 years of age and with increased American Society of Anesthesiologists score (P < .0001). The neurological complication rate in the IONM cohort (range 3.4% to 11.3%; mean 6.4%) was significantly higher compared to the non-IONM cohort (range 1.1% to 1.8%; mean 1.5%) (P < .0001). CONCLUSIONS: The percent of procedures performed with IONM increased. However, these trends do not seem governed by improvement to patient outcomes because the complication rates were higher in the IONM cohort than the non-IONM cohort. PMID- 24239736 TI - Clinical usefulness of coregistered 11C-methionine positron emission tomography/3 T magnetic resonance imaging at the follow-up of acromegaly. AB - OBJECTIVE: This study sought to characterize the utility of coregistered 11C methionine positron emission tomography (MET-PET) with 3-T magnetic resonance imaging (3T MRI) in the diagnosis and follow-up of pituitary adenomas in patients with acromegaly and to compare MET-PET and 18F-fluorodeoxyglucose emission tomography (FDG-PET) for the evaluation of active or recurrent disease. METHODS: This is a prospective observational study. It included a total of 17 patients, 6 patients with a new diagnosis of acromegaly and 11 patients who had previously undergone resection of a confirmed growth hormone-secreting adenoma. The study protocol consisted of preoperative and postoperative evaluation with 3T MRI, and both MET-PET and FDG-PET. Coregistration of 3T MRI/MET-PET was accomplished. RESULTS: In all patients who underwent preoperative imaging, MET-PET demonstrated increased uptake coincident with location of the pituitary lesion on 3T MRI. In the postoperative group, the coregistered 3T MRI/MET-PET demonstrated evidence of residual tumor in all patients with active disease. MET-PET sensitivity was 86% and specificity was 86% for the diagnosis of recurrence. CONCLUSIONS: MET-PET is a sensitive technique for diagnosing persistent acromegaly, and its coregistration with 3T MRI has demonstrated a better definition of the interface, extension, and location of the lesion in the management of active postoperative acromegaly. PMID- 24239737 TI - A correlation between National Institutes of Health funding and bibliometrics in neurosurgery. AB - OBJECTIVE: The relationship between metrics, such as the h-index, and the ability of researchers to generate funding has not been previously investigated in neurosurgery. This study was performed to determine whether a correlation exists between bibliometrics and National Institutes of Health (NIH) funding data among academic neurosurgeons. METHODS: The h-index, m-quotient, g-index, and contemporary h-index were determined for 1225 academic neurosurgeons from 99 (of 101) departments. Two databases were used to create the citation profiles, Google Scholar and Scopus. The NIH Research Portfolio Online Reporting Tools Expenditures and Reports tool was accessed to obtain career grant funding amount, grant number, year of first grant award, and calendar year of grant funding. RESULTS: Of the 1225 academic neurosurgeons, 182 (15%) had at least 1 grant with a fully reported NIH award profile. Bibliometric indices were all significantly higher for those with NIH funding compared to those without NIH funding (P < .001). The contemporary h-index was found to be significantly predictive of NIH funding (P < .001). All bibliometric indices were significantly associated with the total number of grants, total award amount, year of first grant, and duration of grants in calendar years (bivariate correlation, P < .001) except for the association of m-quotient with year of first grant (P = .184). CONCLUSIONS: Bibliometric indices are higher for those with NIH funding compared to those without, but only the contemporary h-index was shown to be predictive of NIH funding. Among neurosurgeons with NIH funding, higher bibliometric scores were associated with greater total amount of funding, number of grants, duration of grants, and earlier acquisition of their first grant. PMID- 24239738 TI - Comparison of symptomatic cerebral spinal fluid leak between patients undergoing minimally invasive versus open lumbar foraminotomy, discectomy, or laminectomy. AB - OBJECTIVE: Minimally invasive spine surgery (MISS) techniques have similar long term outcomes compared to open surgery for patients undergoing 1- or 2-level discectomy, foraminotomy, or laminectomy. However, the rate of cerebrospinal fluid (CSF) leaks with both techniques has not been well established in the literature. This study sought to compare the rate and clinical impact of CSF leak in open lumbar foraminotomy, discectomy, or laminectomy with comparable MISS approaches. METHODS: A total of 863 patients undergoing 1- or 2-level discectomy, foraminotomy, or laminectomy by either MISS an open technique were evaluated for CSF leaks. Variables assessed included operative time, blood loss, CSF leaks, hospital stay, days with lumbar drain, days of postoperative flat bed rest, and postoperative intervention. Statistical analyses include univariate analysis (Student t test, analysis of variance, odds ratio, chi(2)) and bivariate analysis (logistic regression). RESULTS: In the MISS group there were 15 CSF leaks (4.7%), and 49 CSF leaks (9.0%) in the open group. Eight patients in the open group required lumbar drainage, compared to zero patients in the MISS group. Twelve patients required reoperation for persistent CSF leak in the open group, compared to zero patients in the MISS group. Patients undergoing open spine surgery were 2 times more likely to have a CSF leak (odds ratio = 2.3, 95% confidence interval = 1.2 to 3.7, P = .01). Patients undergoing MISS had significantly lower reoperation rates for CSF leak repairs (open = 25% of open CSF leak cases, MISS = 0%, P < .01). CONCLUSIONS: In this study, there was a statistically significant decreased rate of CSF leak between an MISS approach and an open surgical approach. Furthermore, CSF leaks in open surgery have a higher probability of requiring lumbar drainage or reoperation to repair the durotomy. PMID- 24239739 TI - Prospective trial of a short hospital stay protocol after endoscopic endonasal pituitary adenoma surgery. AB - OBJECTIVE: Patients typically remain hospitalized for several days after transsphenoidal surgery for pituitary adenoma resection for reasons including pain control, serial neurological assessments, surveillance for cerebrospinal fluid leak, and management of endocrine issues. We sought to determine whether an evidence-based perioperative care protocol combined with an endoscopic approach could lead to routine and safe discharge on postoperative day 1. METHODS: Our multidisciplinary pituitary group prospectively implemented a perioperative care protocol that emphasizes patient education, early mobilization, and scheduled inpatient and outpatient endocrine assessments on 50 consecutive patients who underwent surgical resection of a pituitary adenoma (82% macroadenomas, 2.1 +/- 0.8 cm, maximum 4.5 cm, 18% microadenomas). Endoscopic endonasal surgery characterized by aggressive tumor resection and avoidance of nasal packing and lumbar drains was used in all cases. Lengths of stay, readmissions, and postoperative outcomes were analyzed. RESULTS: Using the short-stay protocol, 92% (46 of 50) of patients were successfully discharged on postoperative day 1. The average length of stay for all patients was 1.16 +/- 0.55 days (range 1 to 4). Postoperative diabetes insipidus occurred in 16% of patients (8 of 50), was effectively managed on an outpatient basis, and did not delay discharge. Readmission was required in 2 patients, in both cases for delayed presentation of a cerebrospinal fluid leak. CONCLUSIONS: A short-stay protocol allows for an overnight hospital stay for patients after pituitary surgery, with a low rate of complications or readmission. This study offers evidence-based guidelines that may be used to avoid complications and facilitate early discharge after transsphenoidal surgery. PMID- 24239740 TI - Intracranial hemangiopericytoma--our experience in 30 years: a series of 43 cases and review of the literature. AB - OBJECTIVE: Meningeal hemangiopericytoma (HPC) is a rare, aggressive central nervous system tumor that tends to invade locally and to metastasize, and has a high rate of recurrence. METHODS: This study presents a retrospective review of patients managed for intracranial HPC at Rome University Hospital. RESULTS: A total of 43 patients with intracranial HPC were treated from 1980 to 2010. Treatment and follow-up information was available for analysis on 36 patients. The median survival for all patients was 83.5 months after date of diagnosis, with 1-year, 5-year, and 10-year survival rates of 100%, 94.4%, and 72.2%, respectively. Eighteen patients (41.86%) had HPC recurrence. The median time until recurrence was 72.24 months, with 1-year, 5-year, and 10-year progression free survival rates of 98%, 51%, and 29%, respectively. Five patients (11.62%) developed extracranial metastasis. Patients undergoing any form of adjuvant radiation treatment, including external beam radiotherapy, Gamma Knife radiosurgery, and/or proton beam therapy, had no longer median overall survival (OS) (178 vs. 154 months, respectively; P = .2); but did have a significantly improved recurrence-free interval (108 vs. 64 months; P = .04) compared with patients who did not undergo radiation treatment. Tumor characteristics associated with earlier recurrence included size >=7 cm (log-rank, P < .05) and sinus invasion (log-rank, P < .05). CONCLUSIONS: Strategies combining adjuvant radiation with tumor resection seemed to hinder tumor progression, but had no effect on OS or the development of metastases. Greater extent of resection was associated with increased OS (log-rank, P < .05). Anaplastic HPC was associated with reduced OS and with reduced recurrence interval (log-rank, P < .05). PMID- 24239742 TI - Nox4 redox regulation of PTP1B contributes to the proliferation and migration of glioblastoma cells by modulating tyrosine phosphorylation of coronin-1C. AB - Glioblastoma multiforme is a common primary brain tumor in adults and one of the most devastating human cancers. Reactive oxygen species (ROS) generated by NADPH oxidase (Nox) 4 have recently been a focus of attention in the study of glioblastomas, but the molecular mechanisms underlying the actions of Nox4 remain elusive. In this study, we demonstrated that silencing of Nox4 expression by Nox4 targeted siRNA suppressed cell growth and motility of glioblastoma U87 cells, indicating the involvement of Nox4. Furthermore, Nox4-derived ROS oxidized and inactivated protein tyrosine phosphatase (PTP):1B: PTP1B in its active form downregulates cell proliferation and migration. By affinity purification with the substrate-trapping mutant of PTP1B, tyrosine-phosphorylated coronin-1C was identified as a substrate of PTP1B. Its tyrosine phosphorylation level was suppressed by Nox4 inhibition, suggesting that tyrosine phosphorylation of coronin-1C is regulated by the Nox4-PTP1B pathway. Finally, ablation of coronin 1C attenuated the proliferative and migratory activity of the cells. Collectively, these findings reveal that Nox4-mediated redox regulation of PTP1B serves as a modulator, in part through coronin-1C, of the growth and migration of glioblastoma cells, and provide new insight into the mechanistic aspect of glioblastoma malignancy. PMID- 24239743 TI - Identification of a differential expression signature associated with tumorigenesis and metastasis of laryngeal carcinoma. AB - OBJECTIVES: Metastasis is the most significant prognostic factor for laryngeal carcinoma which necessitates the identification of molecular alterations associated with metastasis. The identification of such molecular alterations will not only prove useful in treatment but also provide insight into mechanisms of cancer metastasis. The studies conducted so far have not specifically focused on metastasis or invasion pathways. Therefore we investigated the expression profiles with a pathway focused approach. MATERIALS AND METHODS: Total RNA was extracted from 36 laryngeal tumors and paired cancer free tissue. Expression levels of 88 genes were determined using a PCR array system following cDNA synthesis. Obtained data was used for the calculation of altered expression levels, facilitating relevant algorithms. Significant alterations were determined according to their p-value obtained by Student's t-test. RESULTS: Sixteen genes have shown altered expression when compared with adjacent cancer-free tissue. 2 of these 16 genes have shown differential expression in tumors with neck metastasis in respect to non-metastatic tumors. CONCLUSION: We found that TGFB1, TIMP1, c-Myc, SPARC, COL4A2 and SOX4 show altered expression in laryngeal tumors. c-Myc and SOX4 expression is decreased as laryngeal tumors switch to metastatic phenotype. PMID- 24239741 TI - Usher protein functions in hair cells and photoreceptors. AB - The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber, the tip link, and the linkages that anchor the taller stereocilia's actin cytoskeleton core to the shorter adjacent stereocilia and the elusive mechanotransduction channels, explaining the deafness phenotype when these molecular interactions are perturbed. The conundrum is that photoreceptors lack a synonymous mechanotransduction apparatus, and so a common theory for Usher protein function in the two neurosensory cell types affected in Usher syndrome is lacking. Recent evidence linking photoreceptor cell dysfunction in the shaker 1 mouse model for Usher syndrome to light-induced protein translocation defects, combined with localization of an Usher protein interactome at the periciliary region of the photoreceptors suggests Usher proteins might regulate protein trafficking between the inner and outer segments of photoreceptors. A distinct Usher protein complex is trafficked to the ribbon synapses of hair cells, and synaptic defects have been reported in Usher mutants in both hair cells and photoreceptors. This review aims to clarify what is known about Usher protein function at the synaptic and apical poles of hair cells and photoreceptors and the prospects for identifying a unifying pathobiological mechanism to explain deaf/blindness in Usher syndrome. PMID- 24239744 TI - Antibiotics regulate the immune response in both presence and absence of lipopolysaccharide through modulation of Toll-like receptors, cytokine production and phagocytosis in vitro. AB - The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1beta, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis. PMID- 24239745 TI - Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis. AB - Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE. PMID- 24239746 TI - Seven new cassane furanoditerpenes from the seeds of Caesalpinia minax. AB - A bioassay-guided study led to the isolation of seven new cassane furanoditerpenes, designated as spirocaesalmin B (1), caesalpinin M1 (2), caesalpinin M2 (3), caesalmin E1 (4), caesalmin E2 (5), caesalmin E3 (6), caesalpinin F1 (7) and three known compounds neocaesalpin A(8), neocaesalpin L(9), neocaesalpin L1(10) from the seeds of Caesalpinia minax Hance. Compound structures were determined on the basis of extensive spectroscopic analyses, including X-ray crystallographic analysis, HRESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC, NOESY) methods. Some absolute configurations were confirmed via the circular dichroism (CD) spectra. Compound 1 is the first example of an A-seco rearranged cassane furanoditerpene with an unusual skeleton isolated from the genus Caesalpinia. All compound inhibitory effects on influenza virus neuraminidase (NA) in vitro were valued for the first time. Compared with the positive control (Zanamivir), new compounds were found to show moderate inhibitory activity. PMID- 24239747 TI - Triterpenoids from the fruits of Azadirachta indica (Meliaceae). AB - Four new triterpenoids, indicalilacols A-D (1-4), were isolated from the MeOH extract of the fruits of Azadirachta indica, including a new 19(10->9beta)abeo tirucallane derivative, two new tirucallane-type triterpenoids, and a new euphane type triterpenoid, along with three known tirucallane-type triterpenoids. Their structures were elucidated on the basis of spectroscopic analyses. The absolute configuration of 2 was elucidated by the chemical conversion of 2 into 21-oxo melianodiol 24,25-acetonide. Compounds 2, 6-8 exhibited moderate cytotoxicity against three human cancer cell lines, including multidrug-resistant (MDR) cancer cells (KB-C2). Although compound 5 was not cytotoxic against any of the tested cancer cell lines, 5 showed cytotoxicity against KB-C2 cells in the presence of 2.5 MUM colchicine, suggesting that 5 might have an MDR-reversal effect. PMID- 24239748 TI - Molecular mechanisms of citrus flavanones on hepatic gluconeogenesis. AB - It is well known that hyperglycaemia is the initiating cause of tissue damage associated with type 2 diabetes mellitus and that enhanced hepatic gluconeogenesis may account for the increase in blood glucose levels. The purpose of this work was to investigate the possible actions and mechanisms of three related citrus flavanones, namely hesperidin, hesperetin and naringenin, on hepatic gluconeogenesis and related parameters using isolated perfused rat liver. Hesperetin and naringenin (but not hesperidin) inhibited gluconeogenesis from lactate plus pyruvate, alanine and dihydroxyacetone. The inhibitory effects of these flavanones on gluconeogenesis from lactate and pyruvate (hesperetin IC50 75.6 MUM; naringenin IC50 85.5 MUM) as well as from alanine were considerably more pronounced than those from dihydroxyacetone. The main cause of gluconeogenesis inhibition is the reduction of pyruvate carboxylation by hesperetin (IC50 134.2 MUM) and naringenin (IC50 143.5 MUM) via inhibition of pyruvate transport into the mitochondria. Secondary causes are likely inhibition of energy metabolism, diversion of glucose 6-phosphate for glucuronidation reactions and oxidation of NADH by flavanone phenoxyl radicals. The influence of the structural differences between hesperetin and naringenin on their metabolic effects was negligible. Analytical evidence indicated that the presence of a rutinoside moiety in hesperidin noticeably decreases its metabolic effects, confirming that hesperetin and naringenin interact with intracellular enzymes and mitochondrial or cellular membranes better than hesperidin. Thus, the inhibition of the gluconeogenic pathway by citrus flavanones, which was similar to that of the drug metformin, may represent an attractive novel treatment strategy for type 2 diabetes. PMID- 24239749 TI - Indirect effects of cigarette butt waste on the dengue vector Aedes aegypti (Diptera: Culicidae). AB - Despite major insecticide-based vector control programs, dengue continues to be a major threat to public health in urban areas. The reasons for this failure include the emergence of insecticide resistance and the narrowing of the spectrum of efficient products. Cigarette butts (CBs), the most commonly discarded piece of waste, also represent a major health hazard to human and animal life. CBs are impregnated with thousands of chemical compounds, many of which are highly toxic and none of which has history of resistance in mosquitoes. This study was performed to examine whether exposure to CB alters various biological parameters of parents and their progeny. We examined whether the mosquito changes its ovipositional behaviors, egg hatching, reproductive capacity, longevity and fecundity in response to CB exposure at three different concentrations. Females tended to prefer microcosms containing CBs for egg deposition than those with water only. There were equivalent rates of eclosion success among larvae from eggs that matured in CB and water environments. We also observed decreased life span among adults that survived CB exposure. Extracts of CB waste have detrimental effects on the fecundity and longevity of its offspring, while being attractive to its gravid females. These results altogether indicate that CB waste indirectly affect key adult life traits of Aedes aegypti and could conceivably be developed as a novel dengue vector control strategy, referring to previously documented direct toxicity on the larval stage. But this will require further research on CB waste effects on non-target organisms including humans. PMID- 24239750 TI - New Cryptosporidium parvum subtypes of IIa subfamily in dairy calves from Brazil. AB - Bovine cryptosporidiosis is mainly caused by four distinct species: Cryptosporidium parvum, C. bovis, C. ryanae and C. andersoni. The first, C. parvum, is a major concern in livestock causing economic losses, in addition to public health impact because of its zoonotic characteristics. The present study aimed to determine the occurrence of different species and subtypes of Cryptosporidium using molecular techniques. A total of 143 fecal samples were collected from calves from three dairy farms located in the state of Rio de Janeiro, Brazil. Saturated sugar centrifugal flotation method was used for the microscopic evaluation of the samples. Among these samples, 19.6% (28) were positive by microscopy, and 82.1% (23) of these 28 samples had their diagnosis confirmed by PCR using 18S as gene target. After sequencing, three species of Cryptosporidium were found to infect calves in different age groups. In pre weaning phase (<2 months), 10% (3/30) of the calves were infected with C. parvum, whereas 14.2% (16/113) of post-weaning calves (>=2 months) were observed to be infected with C. andersoni and 1.8% (2/113) by C. ryanae with the latter diagnosed for the first time in the state of Rio de Janeiro. Those samples identified as C. parvum were further characterized at the GP60 locus, and PCR products were cloned. Eight different subtypes (IIaA20G2R1, IIaA20G2R2, IIaA19G2R1, IIaA19G2R2, IIaA18G1R1, IIaA18G2R2, IIaA16G3R2 and IIaA14G2R2) of C. parvum were identified, all belonging to the IIa family subtype, which is considered of high zoonotic potential. The subtypes mentioned above have not yet been detected in Brazilian cattle, and four of these subtypes (IIaA20G2R2, IIaA19G2R2, IIaA18G2R2 and IIaA14G2R2) had not been diagnosed elsewhere in calves until this study. PMID- 24239751 TI - Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine. AB - The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-kappaB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D sufficient swine. There was no difference in the immunostaining for NF-kappaB. Since VDR and CD86 expression are decreased in the setting of melanoma and non melanoma skin cancers, our findings suggest a potential role of vitamin D deficiency in the progression of skin malignancies. PMID- 24239752 TI - Contrasting lexical similarity and formal definitions in SNOMED CT: consistency and implications. AB - OBJECTIVE: To quantify the presence of and evaluate an approach for detection of inconsistencies in the formal definitions of SNOMED CT (SCT) concepts utilizing a lexical method. MATERIAL AND METHOD: Utilizing SCT's Procedure hierarchy, we algorithmically formulated similarity sets: groups of concepts with similar lexical structure of their fully specified name. We formulated five random samples, each with 50 similarity sets, based on the same parameter: number of parents, attributes, groups, all the former as well as a randomly selected control sample. All samples' sets were reviewed for types of formal definition inconsistencies: hierarchical, attribute assignment, attribute target values, groups, and definitional. RESULTS: For the Procedure hierarchy, 2111 similarity sets were formulated, covering 18.1% of eligible concepts. The evaluation revealed that 38 (Control) to 70% (Different relationships) of similarity sets within the samples exhibited significant inconsistencies. The rate of inconsistencies for the sample with different relationships was highly significant compared to Control, as well as the number of attribute assignment and hierarchical inconsistencies within their respective samples. DISCUSSION AND CONCLUSION: While, at this time of the HITECH initiative, the formal definitions of SCT are only a minor consideration, in the grand scheme of sophisticated, meaningful use of captured clinical data, they are essential. However, significant portion of the concepts in the most semantically complex hierarchy of SCT, the Procedure hierarchy, are modeled inconsistently in a manner that affects their computability. Lexical methods can efficiently identify such inconsistencies and possibly allow for their algorithmic resolution. PMID- 24239753 TI - Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper. AB - OBJECTIVE: To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. METHODS: A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. RESULTS: Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. CONCLUSIONS: Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. PMID- 24239754 TI - Effect of pharmacological treatment of osteoporosis in the prevention of pathological vertebral fractures. PMID- 24239755 TI - Identification of Himetobi P virus in the small brown planthopper by deep sequencing and assembly of virus-derived small interfering RNAs. AB - Profiling and assembly of virus-derived small interfering RNAs (siRNAs) using next-generation sequencing technologies have been very useful for identification and diagnosis of a number of plant and invertebrate viruses. In this work, we have conducted high-throughput pyrosequencing and bioinformatic analysis of the small brown planthopper (SBPH, Laodelphax striatellus), and these analyses unexpectedly showed that the Himetobi P virus (HiPV) was present in our laboratory cultures. HiPV was also found to infect our brown planthopper (BPH, Nilaparvata lugens) and the white-backed planthopper (WBPH, Sogatella furcifera) cultures. The majority of the HiPV-derived siRNAs (Hd-siRNAs) were 21 and 22 nucleotides in length and nearly two-thirds of the siRNAs originated from the HiPV genomic RNA strand. The Hd-siRNAs were evenly distributed across the genome and this indicates that the HiPV genome contributes uniformly to production of Hd siRNAs. Although HiPV infection appeared to be innocuous to the SBPH, alterations of gene expressions involved in reproduction, cytoskeleton structure and defense responses such as RNA interference pathways (RNAi) genes were observed. Furthermore, we demonstrated that silencing Agronaute 2 in L. striatellus enhanced HiPV accumulation, and this observation provides evidence for the existence of RNAi defenses against HiPV in the SBPH. PMID- 24239756 TI - KIR2DS4 allelic variants: Differential effects on in utero and intrapartum HIV-1 mother-to-child transmission. AB - KIR2DS4 is the only activating gene within the A haplotype, and alleles of KIR2DS4 can encode either functional (KIR2DS4-f) or non-functional (KIR2DS4-v) variants. To establish the role of KIR2DS4 in the context of HIV-1 mother-to child transmission, we KIR genotyped 145 HIV-1 non-transmitting mothers (NT) and their exposed uninfected infants (EU), and 72 HIV-1 transmitting mothers (TR) and their infected infants [intrapartum (IP), in utero (IU) or IU2 (an IU-enriched infected group)]. The frequency of KIR2DS4-v was significantly higher in IU2 infants compared to EU infants (P=0.022, OR=2.88); this association was more significant amongst AA haplotypes (P=0.004, OR=18.4). Possession of KIR2DS4-f in the mother with absence in the infant (M+I- discordance) was associated with a higher risk of IP transmission (P=0.005, OR=3.84); whilst in M-I+ discordance, infant possession of KIR2DS4-v was associated with increased risk of IU acquisition (P=0.002; OR=6.40). This study highlights the importance of KIR2DS4 in HIV-1 transmission/acquisition. PMID- 24239757 TI - Combined single cell AFM manipulation and TIRFM for probing the molecular stability of multilayer fibrinogen matrices. AB - Adsorption of fibrinogen on various surfaces produces a nanoscale multilayer matrix, which strongly reduces the adhesion of platelets and leukocytes with implications for hemostasis and blood compatibility of biomaterials. The nonadhesive properties of fibrinogen matrices are based on their extensibility, ensuing the inability to transduce strong mechanical forces via cellular integrins and resulting in weak intracellular signaling. In addition, reduced cell adhesion may arise from the weaker associations between fibrinogen molecules in the superficial layers of the matrix. Such reduced stability would allow integrins to pull fibrinogen molecules out of the matrix with comparable or smaller forces than required to break integrin-fibrinogen bonds. To examine this possibility, we developed a method based on the combination of total internal reflection fluorescence microscopy, single cell manipulation with an atomic force microscope and microcontact printing to study the transfer of fibrinogen molecules out of a matrix onto cells. We calculated the average fluorescence intensities per pixel for wild-type HEK 293 (HEK WT) and HEK 293 cells expressing leukocyte integrin Mac-1 (HEK Mac-1) before and after contact with multilayered matrices of fluorescently labeled fibrinogen. For contact times of 500 s, HEK Mac 1 cells show a median increase of 57% of the fluorescence intensity compared to 6% for HEK WT cells. The results suggest that the integrin Mac-1-fibrinogen interactions are stronger than the intermolecular fibrinogen interactions in the superficial layer of the matrix. The low mechanical stability of the multilayer fibrinogen surface may contribute to the reduced cell adhesive properties of fibrinogen-coated substrates. We anticipate that the described method can be applied to various cell types to examine their integrin-mediated adhesion to the extracellular matrices with a variable protein composition. PMID- 24239758 TI - A quantum chemical study of the structures, stability, and spectroscopy of halogen- and hydrogen-boned complexes between cyanoacetaldehyde and hypochlorous acids. AB - The complexes of cyanoacetaldehyde and hypohalous acid (HOX, X=Cl, Br, and I) have been investigated. They can form six different structures (A, B, C, D, E, and F), the former three structures are mainly combined through a N(O)?X halogen bond and the latter three structures are maintained mainly by a N(O)?H hydrogen bond, although other weaker interactions are also present in most structures. The hydrogen-bonded structures are more stable than the respective halogen-bonded structures. The O-H and O-X bonds in the halogen- and hydrogen-bonded complexes are lengthened and show an observed red shift, while those in the weaker secondary interactions are contracted and display a small blue shift. The orbital interactions in NBO analysis and the electron densities in AIM analysis provide useful and reliable information for the strength of each type of interaction in different structures. PMID- 24239759 TI - Biogenic nano-scale silver particles by Tephrosia purpurea leaf extract and their inborn antimicrobial activity. AB - In this paper we report the green synthesis of silver nanoparticles (Ag NPs) using Tephrosia purpurea leaf extract. The biomolecules present in the leaf extract are responsible for the formation of Ag NPs and they found to play dual role of both reducing as well as capping agents. The high crystallinity of Ag NPs is evident from bright circular spot array of SAED pattern and diffraction peaks in XRD profile. The synthesized Ag NPs are found to be nearly spherical ones with size approximately ~20 nm. FTIR spectrum evidences the presence of different functional groups of biomolecules participated in encapsulating Ag NPs and the possible mechanism of Ag NPs formation was also suggested. Appearance of yellow color and surface plasmon resonance (SPR) peak at 425 nm confirms the Ag NPs formation. PL spectra showed decrement in luminescence intensity at higher excitation wavelengths. Antimicrobial activity of Ag NPs showed better inhibitory activity towards Pseudomonas spp. and Penicillium spp. compared to other test pathogens using standard Kirby-Bauer disc diffusion assay. PMID- 24239760 TI - Comparison of two novel in-syringe dispersive liquid-liquid microextraction techniques for the determination of iodide in water samples using spectrophotometry. AB - Two new, rapid methodologies have been developed and applied successfully for the determination of trace levels of iodide in real water samples. Both techniques are based on a combination of in-syringe dispersive liquid-liquid microextraction (IS-DLLME) and micro-volume UV-Vis spectrophotometry. In the first technique, iodide is oxidized with nitrous acid to the colorless anion of ICl2(-) at high concentration of hydrochloric acid. Rhodamine B is added and by means of one step IS-DLLME, the ion-pair formed was extracted into toluene and measured spectrophotometrically. Acetone is used as dispersive solvent. The second method is based on the IS-DLLME microextraction of iodide as iodide/1, 10-phenanthroline iron((II)) chelate cation ion-pair (colored) into nitrobenzene. Methanol was selected as dispersive solvent. Optimal conditions for iodide extraction were determined for both approaches. Methods are compared in terms of analytical parameters such as precision, accuracy, speed and limit of detection. Both methods were successfully applied to determining iodide in tap and river water samples. PMID- 24239761 TI - Synthesis and characterization of Cu(II), Co(II) and Ni(II) complexes of a number of sulfadrug azodyes and their application for wastewater treatment. AB - The azodye ligand (HL(1)) was synthesized from the coupling of sulfaguanidine diazonium salt with 2,4-dihydroxy-benzaldehyde while the two ligands, HL(2) and HL(3), were prepared by the coupling of sulfadiazine diazonium salt with salicylaldehyde (HL(2)) and 2,4-dihydroxy-benzaldehyde (HL(3)). The prepared ligands were characterized by elemental analysis, IR, (1)H NMR and mass spectra. Cu(II), Co(II) and Ni(II) complexes of the prepared ligands have been synthesized and characterized by various spectroscopic techniques like IR, UV-Visible as well as magnetic and thermal (TG and DTA) measurements. It was found that all the ligands behave as a monobasic bidentate which coordinated to the metal center through the azo nitrogen and alpha-hydroxy oxygen atoms in the case of HL(1) and HL(3). HL(2) coordinated to the metal center through sulfonamide oxygen and pyrimidine nitrogen. The applications of the prepared complexes in the oxidative degradation of indigo carmine dye exhibited good catalytic activity in the presence of H2O2 as an oxidant. The reactions followed first-order kinetics and the rate constants were determined. The degradation reaction involved the catalytic action of the azo-dye complexes toward H2O2 decomposition, which can lead to the generation of HO radicals as a highly efficient oxidant attacking the target dye. The detailed kinetic studies and the mechanism of these catalytic reactions are under consideration in our group. PMID- 24239762 TI - Synthesis, spectroscopic, fluorescence properties and biological evaluation of novel Pd(II) and Cd(II) complexes of NOON tetradentate Schiff bases. AB - The solid complexes of Pd(II) and Cd(II) with N,N/bis(salicylaldehyde)4,5 dimethyl-1,2-phenylenediamine (H2L(1)), and N,N/bis(salicylaldehyde)4,5-dichloro 1,2-phenylenediamine (H2L(2)) have been synthesized and characterized by several techniques using elemental analysis (CHN), FT-IR, (1)H NMR, UV-Vis spectra and thermal analysis. Elemental analysis data proved 1:1 stoichiometry for the reported complexes while spectroscopic data indicated square planar and octahedral geometries for Pd(II) and Cd(II) complexes, respectively. The prepared ligands, Pd(II) and Cd(II) complexes exhibited intraligand (pi-pi(*)) fluorescence and can potentially serve as photoactive materials. Thermal behavior of the complexes was studied and kinetic parameters were determined by Coats Redfern method. Both the ligands and their complexes have been screened for antimicrobial activities. PMID- 24239763 TI - Two dimensional cyano-bridged hetero-metallic coordination polymers containing metal???pi interactions. AB - Three cyano bridged hetero-metallic complexes of general formula, [Cu(NH3)2(MU ampy)M(MU-CN)2(CN)2]n [ampy=4-aminomethylpyridine, M=Ni(II) (1), Pd(II) (2) and Pt(II) (3)] have been synthesized and characterized by vibrational (FT-IR and Raman) spectroscopy, single crystal X-ray diffraction, thermal analyses and elemental analyses. The complexes crystallize in triclinic system with space group P-1. In all complexes, M(II) ions are coordinated by four cyano ligands, and four N atoms in the equatorial plane around the Cu atom form a slightly distorted square-planar arrangement, while the slightly distorted octahedral coordination is completed by the cyanide N atoms in the axial positions. In one dimensional structures of all the complexes, [Cu(ampy)](2+) cations and [M(CN)4](2-) anions are linked via bridging cyano ligands. The adjacent one dimensional structures form a 2D network to connect by the MU-ampy bridging ligands. The 2D layers are further linked by metal?pi and hydrogen bonding interactions to generate a three dimensional network. PMID- 24239764 TI - Spectroscopic and biological approach of Ni(II), Cu(II) and Co(II) complexes of 4 methoxy/ethoxybenzaldehyde thiosemicarbazone glyoxime. AB - Two novel vicinal dioxime ligands containing (4-methoxybenzaldehyde thiosemicarbazone glyoxime (L(1)H2) or 4-ethoxybenzaldehyde thiosemicarbazone glyoxime (L(2)H2)) thiosemicarbazone units were synthesized and characterized using (1)H NMR, (13)C NMR, HMQC, MS, infrared and, UV-VIS. spectroscopy, elemental analysis, and magnetic susceptibility measurements. Mononuclear nickel(II), copper(II) and cobalt(II) complexes with a metal:ligand ratio of 1:2 for L(1)H2 and L(2)H2 were also synthesized. The effect of pH and solvent on the absorption spectra of both ligands and complexes was determined. IR spectra show that the ligands act in a bidentate manner and coordinates N4 donor groups of the ligands to Ni(II), Cu(II) and Co(II) ions. The detection of H-bonding (O-H?O) in the [M(LH)2] metal complexes by IR spectra supported the square-planar MN4 coordination of mononuclear complexes. The antimicrobial activities of compounds L(1)H2, L(2)H2, and their Ni(II), Cu(II) and Co(II) complexes were evaluated using the disc diffusion method against 12 bacteria and 4 yeasts. The minimal inhibitory concentrations (MICs) against 7 bacteria and 3 yeasts were also determined. Among the test compounds attempted, L(1)H2, [Ni(L1H)2], [Cu(L1H)2], L2H2, [Ni(L2H)2] and [Cu(L2H)2] showed some activities against certain Gram positive bacteria and some of the yeasts tested. PMID- 24239765 TI - A novel structure for removal of pollutants from wastewater. AB - Dried water hyacinth was subjected to molecular modifications using quantum mechanical calculations. The model simulates the modified plant as 3 cellulose units, one lignin and some metal oxides namely CaO; FeO and Al(OH)3 are attached through O-Linkage. The model suggests the ability to remove inorganic pollutants from wastewater according to unique hydrogen bonding and high total dipole moment. Based on this model microspheres are synthesized in the laboratory from dried water hyacinth and chitosan following self-assembly method. FTIR spectrum of microspheres exhibits only the characteristic bands for raw materials which give strong evidence that the formed material is a composite. The analysis of SEM micrographes of microspheres showed that the fibers of water hyacinth are imbedded in the crosslinked chitosan matrix. Batch adsorption kinetic models revealed that the sorption of lead ions on microsphere was very fast and the equilibrium was rapidly attained within 30 min. and properly correlated with the second-order kinetic model. Different models of isotherm sorption were used to describe the Pb (II) adsorption onto microspheres. From Langmuir isotherm, the maximum adsorption capacity (q(max)) for Pb(II) was 312.5 mg/g, which is about 3 times higher than that of the crude hyacinth. The free energy (E) was 15.798 kJ/mol which shows that the sorption process is endothermic and the mechanism of reaction is an ion-exchange. Even after four cycles of adsorption-desorption, the adsorption capacity was maintained and the decline in efficiency was less than 10%. PMID- 24239766 TI - LXR antagonists induce ABCD2 expression. AB - X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a beta-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCDI gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their beta-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative therapy for X-ALD patients. Since LXR activation was shown to repress ABCD2 expression, we investigated the effects of LXR antagonists in different cell lines. Cells were treated with GSK(17) (a LXR antagonist recently discovered from the GlaxoSmithKline compound collection), 22(S)-hydroxycholesterol (22S-HC, another LXR antagonist) and 22R-HC (an endogenous LXR agonist). We observed up-regulation of ABCD2,ABCD3 and CTNNB1 (the gene encoding for beta-catenin, which was recently demonstrated to induce ABCD2 expression) in human HepG2 hepatoma cells and in X ALD skin fibroblasts treated with LXR antagonists. Interestingly, induction in X ALD fibroblasts was concomitant with a decrease in oxidative stress. Rats treated with 22S-HC showed hepatic induction of the 3 genes of interest. In human, we show by multiple tissue expression array that expression of ABCD2 appears to be inversely correlated with NR1H3 (LXRalpha) expression. Altogether, antagonists of LXR that are currently developed in the context of dyslipidemia may find another indication with X-ALD. PMID- 24239767 TI - Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses. AB - Gaucher disease (GD) and Fabry disease (FD) are two relatively common inherited glycosphingolipidoses caused by deficiencies in the lysosomal glycosidases glucocerebrosidase and alpha-galactosidase A, respectively. For both diseases enzyme supplementation is presently used as therapy. Cells and tissues of GD and FD patients are uniformly deficient in enzyme activity, but the two diseases markedly differ in cell types showing lysosomal accumulation of the glycosphingolipid substrates glucosylceramide and globotriaosylceramide, respectively. The clinical manifestation of Gaucher disease and Fabry disease is consequently entirely different and the response to enzyme therapy is only impressive in the case of GD patients. This review compares both glycosphingolipid storage disorders with respect to similarities and differences. Presented is an update on insights regarding pathophysiological mechanisms as well as recently available biochemical markers and diagnostic tools for both disorders. Special attention is paid to sphingoid bases of the primary storage lipids in both diseases. The value of elevated glucosylsphingosine in Gaucher disease and globotriaosylsphingosine in Fabry disease for diagnosis and monitoring of disease is discussed as well as the possible contribution of the sphingoid bases to (patho)physiology. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. PMID- 24239768 TI - Second generation S1P pathway modulators: research strategies and clinical developments. AB - Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Until recently, major therapeutic treatments have relied on agents requiring injection delivery. In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved as the first oral treatment for relapsing forms of MS. Fingolimod causes down-modulation of S1P1 receptors on lymphocytes which prevents the invasion of autoaggressive T cells into the CNS. In astrocytes, down-modulation of S1P1 by the drug reduces astrogliosis, a hallmark of MS, thereby allowing restoration of productive astrocyte communication with other neural cells and the blood brain barrier. Animal data further suggest that the drug directly supports the recovery of nerve conduction and remyelination. In human MS, such mechanisms may explain the significant decrease in the number of inflammatory markers on brain magnetic resonance imaging in recent clinical trials, and the reduction of brain atrophy by the drug. Fingolimod binds to 4 of the 5 known S1P receptor subtypes, and significant efforts were made over the past 5 years to develop next generation S1P receptor modulators and determine the minimal receptor selectivity needed for maximal therapeutic efficacy in MS patients. Other approaches considered were competitive antagonists of the S1P1 receptor, inhibitors of the S1P lyase to prevent S1P degradation, and anti-S1P antibodies. Below we discuss the current status of the field, and the functional properties of the most advanced compounds. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. PMID- 24239770 TI - Vertebroplasty using calcium phosphate in osteoporotic vertebral compression fractures: how to prevent heterotopic ossifications? PMID- 24239769 TI - A role for Raptor phosphorylation in the mechanical activation of mTOR signaling. AB - The activation of mTOR signaling is necessary for mechanically-induced changes in skeletal muscle mass, but the mechanisms that regulate the mechanical activation of mTOR signaling remain poorly defined. In this study, we set out to determine if changes in the phosphorylation of Raptor contribute to the mechanical activation of mTOR. To accomplish this goal, mouse skeletal muscles were subjected to mechanical stimulation via a bout of eccentric contractions (EC). Using mass spectrometry and Western blot analysis, we found that ECs induced an increase in Raptor S696, T706, and S863 phosphorylation, and this effect was not inhibited by rapamycin. This observation suggested that changes in Raptor phosphorylation might be an upstream event in the pathway through which mechanical stimuli activate mTOR. To test this, we employed a phospho-defective mutant of Raptor (S696A/T706A/S863A) and found that the EC-induced activation of mTOR signaling was significantly blunted in muscles expressing this mutant. Furthermore, mutation of the three phosphorylation sites altered the interactions of Raptor with PRAS40 and p70(S6k), and it also prevented the EC-induced dissociation of Raptor from p70(S6k). Combined, these results suggest that changes in the phosphorylation of Raptor play an important role in the pathway through which mechanical stimuli activate mTOR signaling. PMID- 24239771 TI - In reply. PMID- 24239772 TI - De novo transcriptome analysis of Liriodendron chinense petals and leaves by Illumina sequencing. AB - Liriodendron chinense (Hemsl.) Sarg is an endangered species and occupies a pivotal position in phylogenetic studies of flowering plants, while its genomic resources are limited. In this study, we performed transcriptome sequencing for L. chinense petals and leaves using the Illumina paired-end sequencing technique. Approximately 17.02-Gb clean reads were obtained, and de novo assembly generated 87,841 unigenes, with an average length of 778 bp. Of these, there were 65,535 (74.61%) unigenes with significant similarity to publically available plant protein sequences. There were 3386 genes identified as significant differentially expressed between petals and leaves, among them 2969 (87.68%) were up-regulated and 417 (12.31%) down-regulated in petals. Metabolic pathway analysis revealed that 25 unigenes were predicted to be responsible for the biosynthesis of carotenoids, with 7 genes differentially expressed between these two tissues. This report is the first to identify genes associated with carotenoid biosynthesis in Liriodendron and represents a valuable resource for future genomic studies on the endangered species L. chinense. PMID- 24239773 TI - Imaging the posterior segment of the eye using swept-source optical coherence tomography in myopic glaucoma eyes: comparison with enhanced-depth imaging. AB - PURPOSE: To compare the detection rates of identifying the posterior border of the sclera and lamina cribrosa and measurement reproducibility of scleral and laminar thicknesses using the enhanced depth imaging (EDI) of Heidelberg Spectralis optical coherence tomography (OCT) and swept-source OCT. DESIGN: Cross sectional design. METHODS: Both EDI-OCT and swept-source OCT images were obtained in 32 myopic glaucoma patients. Subfoveal choroidal, subfoveal scleral, and central laminar thicknesses were measured from obtained B-scan images. Each measurement was performed at 3 locations by 2 masked observers. The detection rates and measurement reproducibility were evaluated from selected B-scans. RESULTS: The posterior border of the sclera was visible in 10 eyes (31%) using EDI-OCT. This was improved to be visible in 17 eyes (53%) using swept-source OCT. According to the McNemar chi(2) test, the detection rate of the posterior border of the sclera was significantly different between EDI-OCT and swept-source OCT (P = 0.008). The detection rate of the posterior border of the lamina cribrosa was similar for the 2 devices. In highly myopic eyes, the detection rate of the posterior border of the sclera and lamina cribrosa was not statistically different between EDI-OCT and swept-source OCT. Intersystem ICCs was 0.769 (95% CI, 0.714-0.893) for subfoveal scleral thickness and 0.900 (95% CI, 0.887-0.917) for laminar thickness. The mean subfoveal scleral thickness was 464.32 +/- 213.24 MUm using EDI-OCT and 650.26 +/- 222.30 MUm using swept-source OCT. There was statistical difference in the measured subfoveal scleral thickness by the 2 devices (P = 0.018). CONCLUSIONS: Compared with EDI-OCT, swept-source OCT had an advantage in imaging the posterior sclera. Imaging the lamina cribrosa was similar when using both devices. PMID- 24239774 TI - Eight-year follow-up of posterior chamber phakic intraocular lens implantation for moderate to high myopia. AB - PURPOSE: To assess the long-term clinical outcomes of Implantable Collamer Lens (Visian ICL; STAAR Surgical) implantation for moderate to high myopia. DESIGN: Retrospective observational case series. METHODS: This study evaluated 41 eyes of 41 patients with myopic refractive errors of -4.00 to -15.25 diopters (D) who underwent ICL implantation and routine postoperative examinations. Before surgery, and 1 and 6 months and 1, 4 and 8 years after surgery, we assessed the safety, efficacy, predictability, stability, and adverse events of the surgery. RESULTS: The safety and efficacy indices were 1.13 +/- 0.27 and 0.83 +/- 0.36. At 8 years, 68.3% and 85.4% of the eyes were within 0.5 and 1.0 D, respectively, of the targeted correction. Manifest refraction changes of -0.32 +/- 0.73 D occurred between 1 month and 8 years. The mean endothelial cell loss from preoperative levels was 6.2% at 8 years. Two eyes (4.9%) developed clinically significant symptomatic cataract during the follow-up period. Simultaneous lens extraction and phacoemulsification with IOL implantation was successfully performed in these 2 eyes. CONCLUSIONS: According to our experience, ICL implantation was overall good in measures of safety, efficacy, predictability, and stability for the correction of moderate to high myopia during the 8-year observation period, suggesting its long-term viability as a surgical option for the treatment of such eyes. PMID- 24239775 TI - A method to estimate the amount of neuroretinal rim tissue in glaucoma: comparison with current methods for measuring rim area. AB - PURPOSE: To test whether the minimum rim area assessed by spectral domain optical coherence tomography (SD-OCT), based on the shortest distance from the Bruch membrane opening (BMO) to the inner limiting membrane, corresponds more closely to retinal nerve fiber layer (RNFL) thickness and visual field mean deviation (MD) than current rim measures in early glaucoma. DESIGN: Prospective cross sectional study. METHODS: We studied 221 participants with non-endstage glaucoma or high-risk ocular hypertension and performed standard automated perimetry. We received SD-OCT and confocal scanning laser ophthalmoscopy (CSLO) scans on the same day. Rim area measured by CSLO was compared with 3 SD-OCT rim measures from radial B-scans: horizontal rim area between BMO and inner limiting membrane within the BMO plane; mean minimum rim width (BMO-MRW); and minimum rim area (BMO MRA) optimized within sectors and then summed. Correlations between these measures and either MD from perimetry or RNFL thickness from SD-OCT were compared using the Steiger test. RESULTS: RNFL thickness was better correlated with BMO MRA (r = 0.676) or BMO-MRW (r = 0.680) than with either CSLO rim area (r = 0.330, P < 0.001) or horizontal rim area (r = 0.482, P < 0.001). MD was better correlated with BMO-MRA (r = 0.534) or BMO-MRW (r = 0.546) than with either CSLO rim area (r = 0.321, P < 0.001) or horizontal rim area (0.403, P < 0.001). The correlation between MD and RNFL thickness was r = 0.646. CONCLUSIONS: Minimum rim measurements from SD-OCT are significantly better correlated to both RNFL thickness and MD than rim measurements within the BMO plane or based on the clinical disc margin. They provide new structural parameters for both diagnostic and research purposes in glaucoma. PMID- 24239776 TI - Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. AB - BACKGROUND & AIMS: The Hedgehog signaling pathway contributes to cholangiocarcinoma biology. However, canonical Hedgehog signaling requires cilia, and cholangiocarcinoma cells often do not express cilia. To resolve this paradox, we examined non-canonical (G-protein coupled, pertussis toxin sensitive) Hedgehog signaling in cholangiocarcinoma cells. METHODS: Human [non-malignant (H69), malignant (HuCC-T1 and Mz-ChA-1)] and rat [non-malignant (BDE1 and NRC), and malignant (BDEneu)] cell lines were employed for this study. A BDE(DeltaLoop2) cell line with the dominant-negative receptor Patched-1 was generated with the Sleeping Beauty transposon transfection system. RESULTS: Cilia expression was readily identified in non-malignant, but not in malignant cholangiocarcinoma cell lines. Although the canonical Hh signaling pathway was markedly attenuated in cholangiocarcinoma cells, they were chemotactic to purmorphamine, a small molecule direct Smoothened agonist. Purmorphamine also induced remodeling of the actin cytoskeleton with formation of filopodia and lamellipodia-like protrusions. All these biological features of cell migration were pertussis toxin sensitive, a feature of G-protein coupled (Gis) receptors. To further test the role of Hedgehog signaling in vivo, we employed a syngeneic orthotopic rat model of cholangiocarcinoma. In vivo, genetic inhibition of the Hedgehog signaling pathway employing BDE(DeltaLoop2) cells or pharmacological inhibition with a small molecule antagonist of Smoothened, vismodegib, was tumor and metastasis suppressive. CONCLUSIONS: Cholangiocarcinoma cells exhibit non-canonical Hedgehog signaling with chemotaxis despite impaired cilia expression. This non-canonical Hedgehog signaling pathway appears to contribute to cholangiocarcinoma progression, thereby, supporting a role for Hedgehog pathway inhibition in human cholangiocarcinoma. PMID- 24239777 TI - N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape. AB - BACKGROUND & AIMS: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. METHODS: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti HBs as a control group. Recombinant HBsAg bearing the most frequent N glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. RESULTS: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. CONCLUSIONS: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area. PMID- 24239778 TI - The pattern and extent of retrograde transsynaptic transport of WGA-Alexa 488 in the phrenic motor system is dependent upon the site of application. AB - The first aim of the study was to determine if WGA-Alexa 488 would undergo retrograde transsynaptic transport in the phrenic motor system as we have shown with WGA-HRP in a previous study. The advantage of using WGA-Alexa 488 is that labeled neurons could be isolated and analyzed for intracellular molecular mechanisms without exposing tissue sections to chemicals for histochemical staining. The second aim of the study was to investigate the pattern and extent of labeling that occurs when WGA-Alexa 488 is applied to the cervical phrenic nerve as compared to intradiaphragmatic injection. After injecting the hemidiaphragm ipsilateral to a C2 spinal cord hemisection, WGA-Alexa 488 presumably diffused to the contralateral hemidiaphragm and labeled the phrenic nuclei bilaterally. In all animals with hemidiaphragmatic injection, the rostral ventral respiratory group (rVRG) was also labeled bilaterally in the medulla. Thus, injection of WGA-Alexa 488 into the diaphragm results in retrograde transsynaptic transport in the phrenic motor system. After applying WGA-Alexa 488 to the ipsilateral intact cervical phrenic nerve in both C2 hemisected rats and rats with a sham hemisection, only ipsilateral phrenic neurons were labeled; there was no labeling of the rVRG or any other center in the medulla. These results suggest that WGA-Alexa 488 must be applied in the vicinity of the phrenic myoneural junction where there is a high concentration of WGA receptors in order for transsynaptic transport to occur. The present study provides investigators with a new tool to study plasticity in the respiratory system after spinal cord injury. PMID- 24239780 TI - Utilization of in situ ELISA method for examining Trk receptor phosphorylation in cultured cells. AB - BACKGROUND: Trk receptor tyrosine kinases regulate multiple important neuronal processes during the development and in the adulthood. Tyrosine phosphorylation of Trk serves as the initial step in the Trk signaling pathway and indicates receptor' autocatalytic activity. However, methods allowing simple and large scale Trk phosphorylation analyses in cultured cells are lacking. NEW METHOD: We describe an in situ phospho-Trk ELISA (enzyme-linked immunosorbent assay) method where cell culture, receptor stimulation and Trk phosphorylation analysis are all performed on the same multiwell plate. RESULTS: In situ phospho-Trk ELISA readily and specifically detects neurotrophin-induced Trk phosphorylation in cultured cells. A proof-of-concept small molecule screening of a library composed of 2000 approved drugs and other bioactive compounds was carried out using this novel method. COMPARISON WITH EXISTING METHODS: In situ phospho-Trk ELISA utilizes the principles and advantages of conventional sandwich ELISA in an in situ context. CONCLUSIONS: We describe a novel method that can be efficiently used to examine Trk receptor phosphorylation in cultured cells. Principally similar methods can be developed to examine the levels and signaling of any intracellular protein. PMID- 24239779 TI - Validation of the isotropic fractionator: comparison with unbiased stereology and DNA extraction for quantification of glial cells. AB - BACKGROUND: The "isotropic fractionator" (IF) is a novel cell counting technique that homogenizes fixed tissue, recovers cell nuclei in solution, and samples and quantifies nuclei by extrapolation. Studies using this technique indicate that the ratio of glia to neurons in the human brain is approximately 1:1 rather than the 10:1 or 50:1 ratio previously assumed. Although some results obtained with the IF have been similar to those obtained by stereology, the IF has never been calibrated or validated. It is conceivable that only a fraction of glial cell nuclei are recovered intact or recognized after the homogenization step. NEW METHOD: To rule out this simple explanation for the claim of a 1:1 glia-neuron ratio, we compared cell numbers obtained from adjacent, weight-normalized samples of human and macaque monkey white matter using three techniques: the IF, unbiased stereology of histological sections in exhaustively sectioned samples, and cell numbers calculated from DNA extraction. RESULTS AND COMPARISON OF METHODS: In primate forebrains, the IF yielded 73,000-90,000 nuclei/mg white matter, unbiased stereology yielded 75,000-92,000 nuclei/mg, with coefficients of error ranging from 0.013 to 0.063, while DNA extraction yielded only 4000-23,000 nuclei/mg in fixed white matter tissues. CONCLUSIONS: Since the IF revealed about 100% of the numbers produced by unbiased stereology, there is no significant underestimate of glial cells. This confirms the notion that the human brain overall contains glial cells and neurons with a ratio of about 1:1 - far from the originally assumed ratio of 10:1 in favor of glial cells. PMID- 24239781 TI - Development of an in vitro test system for assessment of male, reproductive toxicity. AB - There is a need for improved reproductive toxicology assays that do not require large numbers of animals but are sensitive and informative. Therefore, Staput velocity-sedimentation separation followed by culture of specific mouse testicular cells was used as such a system. The specificity of separation was assessed using immunocytochemistry to identify spermatids, spermatocytes and spermatogonia. The efficacy of the system to detect toxicity was then evaluated by analysing the effects of hydrogen peroxide (H2O2) by the terminal uridine deoxynucleotide end-labelling (TUNEL) assay to show the rate of apoptosis induced among the different types of germ cells. We found that 2 h of treatment at both 1 and 10 MUM induced increases of over ~10-fold in the percentage of apoptotic cells (p<=0.001), confirming that testicular germ cells are prone to apoptosis at very low concentrations of H2O2. It was also demonstrated for the first time for this compound that spermatogonia are significantly more susceptible than spermatocytes, which are more affected than spermatids. This reflects the proportion of actively dividing cells in these cell types, suggesting a mechanism for the differential sensitivity. The approach should thus form the basis of a useful test system for reproductive and genetic toxicology in the future. PMID- 24239782 TI - AhR signalling and dioxin toxicity. AB - Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years. Although TCDD has been classified by the WHO as a human carcinogen, its carcinogenic potential to humans is not clearly demonstrated. It was first believed that AhR activation accounted for most, if not all, biological properties of dioxins. However, certain AhR agonists found in vegetables do not induce chloracne, and other chemicals, in particular certain therapeutic agents, may induce a chloracne-like syndrome without activating AhR. It is time to rethink the mechanism of dioxin toxicity and analyse in more details the biological events following exposure to these compounds and other AhR agonists, some of which have a very different chemical structure than TCDD. In particular various food-containing AhR agonists are non-toxic and may on the contrary have beneficial properties to human health. PMID- 24239783 TI - Kinesin-dependent motility generation as target mechanism of cadmium intoxication. AB - The anterograde vesicle transport within neurons critically depends on microtubules and on the activity of kinesin. The present study demonstrates that cadmium ions inhibit the in vitro assembly of microtubules from tubulin, whereby at high cadmium levels (~500 MUM) unstructured protein aggregates were formed. Cadmium ions also significantly lower both the ATPase and motility activity of neuron-specific kinesin KIF5A in concentration-dependent manner. For the inhibition of KIF5A ATPase activity, an IC50 value of 10.4+/-1.5 MUM was determined. Inhibition could be widely compensated by addition of EGTA, but not by addition of thiols. The inhibitory effect of cadmium on KIF5A was considerably weakened by increasing ATP concentration. As nucleoside triphosphate binding is known to be accompanied by conformational changes within the kinesin motor domain, it might be suggested that these changes protect the motor domain against cadmium. The effects of cadmium ions on the kinesin-microtubule motility generating system are considered to contribute to the development of neuronal disorders caused by cadmium intoxication. PMID- 24239785 TI - Antidepressant-induced sexual dysfunction in men. AB - Most of the available antidepressant medications, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and dual noradrenergic/serotonergic reuptake inhibitors have been reported to be associated with sexual dysfunction in both sexes. This manuscript reviews evidence concerning the relative incidence of treatment emergent sexual dysfunction in men being treated with antidepressant drugs. Both double-blind controlled trials and large clinical series report a high incidence of sexual dysfunction, especially ejaculatory delay, with serotonergic drugs. The incidence of sexual dysfunction in men appears to be much lower with drugs whose primary mechanism of action involves adrenergic or dopaminergic systems. PMID- 24239786 TI - Conditioned taste avoidance induced by Delta(9)-tetrahydrocannabinol in the Fischer (F344) and Lewis (LEW) rat strains. AB - Although Fischer (F344) and Lewis (LEW) rats differ in their sensitivity to the rewarding effects of ?(9)-tetrahydrocannabinol (THC), no data have been reported on differences in their sensitivity to the drug's aversive effects, a limiting factor in drug use and abuse. Examining the degree of differences (if any) in such effects in these strains may help further characterize possible genetic factors important to abuse vulnerability. Accordingly, the aversive effects of THC (1-5.6 mg/kg; intraperitoneal) were examined in 32F344 and 32 LEW subjects using the conditioned taste avoidance (CTA) procedure. Thermoregulation was assessed following an acute injection of THC (same as CTA groups) after a week washout period following the last trial. Subjects in both strains displayed dose dependent THC-induced taste avoidance, with no significant strain difference. THC induced dose-dependent decreases in core body temperature in both strains. LEW subjects displayed lower core body temperatures than F344 rats, although this effect was independent of THC and was likely stress related. These results were discussed in terms of the nature of THC-induced taste avoidance and the basis of strain differences in the aversive effects of drugs of abuse. PMID- 24239787 TI - Serotonin 1A receptors and sexual behavior in male rats: a review. AB - Serotonin plays an important role in male sexual behavior. Many studies have been performed on the pivotal role of 5-HT1A receptors in sexual behavior. Overall, 5 HT1A receptors do not appear to be involved under normal circumstances, but become very important under conditions of elevated serotonin levels in sexual behavior. 5-HT1A receptor agonists facilitate ejaculatory behavior in male rats, while inhibiting copulatory behavior. Three different phases can be distinguished in rats' sexual cycle, the introductory (precopulatory), the copulatory and the executive (ejaculatory) phases. Different mechanisms and brain regions are involved in these phases. The mechanisms, brain regions and the possible involvement of 5-HT and 5-HT1A receptors in the appropriate phases in male rat sexual behavior will be discussed in the current review. PMID- 24239788 TI - Opioids and sexual reward. AB - Various lines of research indicate that sexual reward is mediated by opioids in both males and females. In the first part I review basic ideas about sexual reward in humans followed by a description of what is known in rodents, where most of the studies have been done. Although a direct method to measure opioid release during mating is not yet available, there is a substantial amount of indirect evidence in humans and animals indicating that opioids are released during the execution of sexual behavior. Studies using the conditioned place preference (CPP) method where the effects of opioids upon sex induced reward have been evaluated will also be described. Evidence will also be presented indicating that the medial preoptic area (MPOA) plays a crucial role in the expression of opioid mediated sex-reward in males and females. This area is also important in other naturally occurring reward related behaviors such as singing. Opioids might be part of a system that mediates the rewarding properties of natural behaviors that are intrinsically rewarding. PMID- 24239784 TI - Pharmacology of serotonin and female sexual behavior. AB - In this review, first a historical perspective of serotonin's (5-HT) involvement in female sexual behavior is presented. Then an overview of studies implicating 5 HT is presented. The effect of drugs that increase or decrease CNS levels of 5-HT is reviewed. Evidence is presented that drugs which increase 5-HT have negative effects on female sexual behavior while a decrease in 5-HT is associated with facilitation of sexual behavior. Studies with compounds that act on 5-HT1, 5-HT2 or 5-HT3 receptors are discussed. Most evidence indicates that 5-HT1A receptor agonists inhibit sexual behavior while 5-HT2 or 5-HT3 receptors may exert a positive influence. There is substantial evidence to support a role for 5-HT in the modulation of female consummatory sexual behavior, but studies on the role of 5-HT in other elements of female sexual behavior (e.g. desire, motivation, sexual appetite) are few. Future studies should be directed at determining if these additional components of female sexual behavior are also modulated by 5-HT. PMID- 24239789 TI - Effects of oxytocin on nicotine withdrawal in rats. AB - Development of medications that attenuate symptoms of nicotine withdrawal may be useful for facilitating smoking cessation. The neuropeptide oxytocin (OXY) decreases withdrawal signs and other addiction-related effects of several drugs of abuse in animals, but has not been examined in a preclinical model of nicotine addiction. The goal of this study was to examine the effects of OXY on nicotine withdrawal in rats, measured as increases in somatic signs and elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during antagonist-precipitated withdrawal from a chronic nicotine infusion. Effects of OXY on baseline ICSS thresholds in non-dependent rats were also evaluated. OXY (0.06 - 1.0mg/kg, i.p.) blocked withdrawal-induced elevations in somatic signs in nicotine-dependent rats without affecting somatic signs in non-dependent rats. In contrast, OXY did not affect nicotine withdrawal-induced elevations in ICSS thresholds. Relatively high doses of OXY (0.75 or 2.0mg/kg) elevated baseline ICSS thresholds in non-dependent rats. These findings demonstrate that OXY blocks somatic signs but not elevations in ICSS thresholds during antagonist precipitated nicotine withdrawal. The ability of higher OXY doses to elevate baseline ICSS thresholds in non-dependent rats may reflect an aversive and/or motoric effect. These data suggest that OXY-based medications may be useful for treating the somatic component of the nicotine withdrawal syndrome, but may not be effective in attenuating withdrawal-induced anhedonia. PMID- 24239790 TI - Combination transcranial direct current stimulation and virtual reality therapy for upper extremity training in patients with subacute stroke. AB - OBJECTIVE: To investigate the effects of combination cathodal transcranial direct current stimulation (tDCS) and virtual reality (VR) therapy for upper extremity (UE) training in patients with subacute stroke. DESIGN: Pilot randomized controlled trial. Patients were randomly assigned to 1 of 3 groups: group A received cathodal tDCS, group B received VR, and group C received combination therapy (cathodal tDCS was simultaneously applied during VR therapy). SETTING: University hospital. PARTICIPANTS: Patients (N=59) with impaired unilateral UE motor function after stroke. INTERVENTION: Fifteen sessions of treatment over a 3 week period. MAIN OUTCOME MEASURES: The Modified Ashworth Scale, manual muscle test (MMT), Manual Function Test (MFT), Fugl-Meyer Scale (FMS), and Box and Block Test were used to assess UE function. To evaluate activities of daily living, the Korean-Modified Barthel Index (K-MBI) was used. All outcomes were measured before and immediately after treatment. RESULTS: After treatment, all groups demonstrated significant improvements in MMT, MFT, FMS, and K-MBI scores. The change in MFT and FMS scores was different between the 3 groups. Post hoc analysis revealed that the improvement of MFT and FMS scores in group C was significantly higher than those of the other 2 groups. CONCLUSIONS: In the present pilot study, the combination of brain stimulation using tDCS and peripheral arm training using VR could facilitate a stronger beneficial effect on UE impairment than using each intervention alone. This combination therapy might be a helpful method to enhance recovery of the paretic UE in patients with stroke. PMID- 24239791 TI - Hair as a long-term retrospective cortisol calendar in orang-utans (Pongo spp.): new perspectives for stress monitoring in captive management and conservation. AB - This study examined whether the method of hair cortisol analysis is applicable to orang-utans (Pongo spp.) and can help to advance the objective monitoring of stress in non-human primates. Specifically, we examined whether fundamental prerequisites for hair cortisol analysis are given in orang-utans and, subsequently, whether segmental hair analysis may provide a retrospective calendar of long-term cortisol levels. For this, hair samples were examined from 71 zoo-living orang-utans (38 males, mean age=22.5years; 33 females, mean age=24years) for which detailed records of past living conditions were available. Hair samples were cut from defined body regions and were analyzed either in full length or in segments. Results showed that hair cortisol concentrations (HCC) were unrelated to age or sex of the individual animal. HCC were found to be higher in orang-utans, with perceived long-term stressful periods (mean HCC=43.6+/-26.5pg/mg, n=13) compared to animals without perceived stressful periods (19.3+/-5.5pg/mg, n=55, P<0.001). In non-stressed animals, segmental hair analyses revealed that HCC was stable along the hair shaft even when hair reached >40cm. The possibility of obtaining a retrospective calendar of stress-related cortisol changes through hair analysis was further supported by data of three case studies showing close correspondence between the segmental HCC results and keeper reports of stress exposure during the respective time periods. Finally, low within-animal variation in HCC from different body regions (CV%: 14.3) suggested that this method may also be applicable to naturally shed hair, e.g., as found in nests of wild orang-utans and other great apes. Therefore, using HCC may provide an ideal non-invasive tool for both captive management as well as conservation in orang-utans and potentially other great apes. PMID- 24239792 TI - Validation and application of noninvasive glucocorticoid and thyroid hormone measures in free-ranging Hawaiian monk seals. AB - We validate fecal glucocorticoid (GC) and thyroid (T3) hormone metabolite measures in the Critically Endangered Hawaiian monk seal for the first time, and examine variation in the concentrations of these hormones in individuals across the species' range. We test hypotheses that monk seals from declining subpopulations have relatively high GCs and low T3 on average suggesting impacts of food limitation, and that this hormone pattern is more apparent in immature animals compared to adults, as food limitation is specifically indicated as a principal cause of poor body condition and survival of juvenile monk seals. We opportunistically sampled scat from 84 individually identifiable monk seals during the 2010 breeding season from two geographic regions, the main Hawaiian Islands (MHI) and the Northwestern Hawaiian Islands (NWHI). The MHI subpopulation of monk seals is growing, whereas subpopulations at many sites in the NWHI are in decline. Best fit general linear models predicting variation in GCs and T3 (examined separately) were similar (after accounting for significantly elevated hormone concentrations associated with molt and possibly lactation); both included sample date, region, and monk seal age as predictors. GC concentrations were significantly lower in MHI versus NWHI monk seals and decreased as the breeding season progressed. T3 concentrations were significantly lower in immature monk seals compared to adults. GC and T3 concentrations were positively correlated at 4 NWHI sites; prey may be adequate for physiological growth or maintenance at these sites but relatively stressful to acquire. GCs were highest at French Frigate Shoals, (a NWHI site) while T3 was relatively low here, indicating a possible signal of food limitation. GCs were lowest in the MHI. Disturbance associated with living near a high human population in the MHI appears to impact monk seal physiology less than other stressors encountered in the remote and highly protected NWHI where human presence is extremely low. PMID- 24239793 TI - Temperature dependent action of growth hormone on somatic growth and testicular activities of the catfish, Clarias batrachus. AB - Effects of growth hormone on somatic growth and testicular activities were studied during late quiescence and early recrudescence phases of the reproductive cycle of the catfish, Clarias batrachus. The administration of exogenous growth hormone (GH) during the late quiescence phase (December-January; ambient water temperature-15.2+/-1 degrees C) did not influence the somatic growth as well as the testicular activity, as no change in body weight, testis weight, plasma level of insulin-like growth factor I (IGF-I) and testicular morphology was detected following GH treatment, though the plasma testosterone was marginally increased. While during the early recrudescence phase (March-April; ambient water temperature-28.1+/-2 degrees C), GH treatment promoted the production of insulin like growth factor-I and testicular steroidogenic activity in a dose dependent manner, as was evident from the significant increase in the circulating levels of testosterone and estradiol-17beta. GH treatment also increased body weight, testicular weight and gonadosomatic index, suggesting its involvement in testicular development. The GH treatment promoted spermatogonial proliferation and accelerated the spermatogenic process in the present catfish. These results, thus, suggest that GH influences the somatic growth and testicular activities depending on the temperature of the rearing water; warmer temperature and longer photoperiod promote testicular steroidogenic and spermatogenic activities in fish. This study has immense practical use in fisheries science. PMID- 24239794 TI - Metabolic response to a glucagon challenge varies with adiposity and life-history stage in fasting northern elephant seals. AB - Metabolic adaptations for extended fasting in wildlife prioritize beta-oxidation of lipids and reduced glucose utilization to support energy metabolism. The pancreatic hormone glucagon plays key roles in regulating glycemia and lipid metabolism during fasting in model species but its function in wildlife species adapted for extended fasting is not well understood. Northern elephant seals (NES) undergo natural fasts of 1-3months while under constraints of high nutrient demands including lactation and development. We performed a glucagon challenge on lactating, molting and developing NES, early and late in their natural fasts, to examine the impact of this important regulatory hormone on metabolism. Glucagon caused increases in plasma glucose, insulin, fatty acids, ketones and urea, but the magnitude of these effects varied widely with adiposity and life-history stage. The strong impact of adiposity on glucose and insulin responses suggest a potential role for adipose derived factors in regulating hepatic metabolism and pancreatic sensitivity. Elevations in plasma glucose in response to glucagon were strongly associated with increases in protein catabolism, suggesting negative impacts of elevated glucagon on protein sparing. Glucagon promoted rapid ketone accumulation suggesting that low ketoacid levels in NES reflect low rates of production. These results demonstrate strong metabolic impacts of glucagon and support the idea that glucagon levels are downregulated in the context of metabolic adaptation to extended fasting. These results suggest that the regulation of carbohydrate and lipid metabolism in NES changes with adiposity, fasting duration and under various constraints of nutrient demands. PMID- 24239795 TI - Application of intracytoplasmic sperm injection (ICSI) for fertilization and development in birds. AB - Intracytoplasmic sperm injection (ICSI) technology in birds has been hampered due to opacity of oocyte. We developed ICSI-assisted fertilization and gene transfer in quail. This paper reviews recent advances of our ICSI experiments. The oocyte retrieved from the oviduct and a quail sperm was injected into the oocyte under a stereomicroscope. The oocyte was cultured for 24h at 41 degrees C under 5% CO2 in air. The fertilization and development was assessed by microscopic observation. The fertility rate ranged 12-18% and development varied from stage II to V in trials. To improve the fertility rate, phospholipase C (PLC) zeta was injected with a sperm. It was increased to 37-50%. Furthermore, injection of inositol trisphosphate increased to over 85%. Quail oocyte can be fertilized with chicken sperm and so can testicular elongated spermatid. To extend embryonic development, chicken eggshell was used as a surrogate culture at 37 degrees C after the 24h incubation at 41 degrees C under 5% CO2 in air. It survived up to 2days thereafter. Finally, gene transfer was attempted in quail egg. The sperm membrane was disrupted with Triton X-100 (TX-100) and was injected with PLCzeta cRNA and enhanced green fluorescent protein (EGFP) gene in oocyte. The GFP expression was evaluated at 24h incubation at 41 degrees C under 5% CO2 in air in the embryos. While the expression was not detected in the control oocytes, the experimental treatment induced blastoderm development (44%) of the oocytes and 86% of blastoderm showed fluorescent emission. In addition, PCR analysis detected EGFP fragments in 50% of GFP-expressing blastoderm. Our ICSI method may be the first step toward the production of transgenic birds. PMID- 24239796 TI - The modulation of catecholamines on immune response of scallop Chlamys farreri under heat stress. AB - Catecholamines (CAs) play key roles in mediating the physiological responses to various stresses. In the present study, the expression of CA-related genes were examined in the hemocytes of scallop Chlamys farreri under heat stress, and several immune or metabolism-related parameters were investigated after heat stress and adrenoceptor antagonist stimulation. After the scallops were cultured at 28 degrees C, the mRNA expression level of dopa decarboxylase (CfDDC) and alpha-adrenoceptor (CfalphaAR) increased significantly (P<0.01), whereas that of monoamine oxidase (CfMAO) was down-regulated in the first 6h (P<0.05), and then up-regulated to the maximum level at 24h (P<0.01). In the hemocytes of scallops injected with adrenoceptor antagonist, the expression levels of peptidoglycan recognition protein (CfPGRP-S1) and C-type lectin (CfLec-1) began to increase significantly at 2 and 3h post propranolol and high temperature treatment, respectively (P<0.01). While the up-regulation of heat shock protein 70 (CfHSP70) post heat stress was significantly inhibited by prazosin injection (P<0.01), and that of hexokinase (CfHK) was inhibited by both prazosin and propranolol injection (P<0.01). Moreover, the remarkable increase of relative specific activity of SOD in the hemolymph post heat stress (P<0.01) was further up regulated early after prazosin or propranolol injection (P<0.01), while that of the relative anti-bacterial ability was down-regulated by prazosin or propranolol treatment (P<0.01). These results collectively indicated that the catecholaminergic neuroendocrine system in scallop could be activated by heat stress to release CAs, which subsequently modulated the immune response and energy metabolism via alpha- and beta-adrenoceptors. PMID- 24239797 TI - Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump. AB - AIMS: Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. METHODS AND RESULTS: We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count >=25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. CONCLUSIONS: In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes. PMID- 24239798 TI - Intermittent hypoxia-induced increases in reactive oxygen species activate NFATc3 increasing endothelin-1 vasoconstrictor reactivity. AB - Sleep apnea (SA), defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension, peripheral vascular disease, stroke, and sudden cardiac death. We have shown that intermittent hypoxia with CO2 supplementation (IH), a model for SA, increases blood pressure and circulating ET-1 levels, upregulates lung pre-pro ET-1 mRNA, increases vasoconstrictor reactivity to ET-1 in rat small mesenteric arteries (MA) and increases vascular reactive oxygen species (ROS). NFAT activity is increased in the aorta (AO) and MA of mice exposed to IH in an ET-1-dependent manner, and the genetic ablation of the isoform NFATc3 prevents IH-induced hypertension. We hypothesized that IH causes an increase in arterial ROS generation, which activates NFATc3 to increase vasoconstrictor reactivity to ET-1. In support of our hypothesis, we found that IH increases ROS in AO and MA. In vivo administration of the SOD mimetic tempol during IH exposure prevents IH-induced increases in NFAT activity in mouse MA and AO. We found that IH causes an NFATc3 dependent increase in vasoconstrictor reactivity to ET-1, accompanied by an increase in vessel wall [Ca2+]. Our results indicate that IH exposure causes an increase in arterial ROS to activate NFATc3, which then increases vasoconstrictor reactivity and Ca2+ response to ET-1. These studies highlight a novel regulatory pathway, and demonstrate the potential clinical relevance of NFAT inhibition to prevent hypertension in SA patients. PMID- 24239799 TI - Predicting medical complications after spine surgery: a validated model using a prospective surgical registry. AB - BACKGROUND CONTEXT: The possibility and likelihood of a postoperative medical complication after spine surgery undoubtedly play a major role in the decision making of the surgeon and patient alike. Although prior study has determined relative risk and odds ratio values to quantify risk factors, these values may be difficult to translate to the patient during counseling of surgical options. Ideally, a model that predicts absolute risk of medical complication, rather than relative risk or odds ratio values, would greatly enhance the discussion of safety of spine surgery. To date, there is no risk stratification model that specifically predicts the risk of medical complication. PURPOSE: The purpose of this study was to create and validate a predictive model for the risk of medical complication during and after spine surgery. STUDY DESIGN/SETTING: Statistical analysis using a prospective surgical spine registry that recorded extensive demographic, surgical, and complication data. Outcomes examined are medical complications that were specifically defined a priori. This analysis is a continuation of statistical analysis of our previously published report. METHODS: Using a prospectively collected surgical registry of more than 1,476 patients with extensive demographic, comorbidity, surgical, and complication detail recorded for 2 years after surgery, we previously identified several risk factor for medical complications. Using the beta coefficients from those log binomial regression analyses, we created a model to predict the occurrence of medical complication after spine surgery. We split our data into two subsets for internal and cross-validation of our model. We created two predictive models: one predicting the occurrence of any medical complication and the other predicting the occurrence of a major medical complication. RESULTS: The final predictive model for any medical complications had a receiver operator curve characteristic of 0.76, considered to be a fair measure. The final predictive model for any major medical complications had receiver operator curve characteristic of 0.81, considered to be a good measure. The final model has been uploaded for use on SpineSage.com. CONCLUSION: We present a validated model for predicting medical complications after spine surgery. The value in this model is that it gives the user an absolute percent likelihood of complication after spine surgery based on the patient's comorbidity profile and invasiveness of surgery. Patients are far more likely to understand an absolute percentage, rather than relative risk and confidence interval values. A model such as this is of paramount importance in counseling patients and enhancing the safety of spine surgery. In addition, a tool such as this can be of great use particularly as health care trends toward pay-for-performance, quality metrics, and risk adjustment. To facilitate the use of this model, we have created a website (SpineSage.com) where users can enter in patient data to determine likelihood of medical complications after spine surgery. PMID- 24239800 TI - Does physical activity influence the relationship between low back pain and obesity? AB - BACKGROUND CONTEXT: Evidence supporting an association between obesity and low back pain (LBP) continues to grow; yet little is known about the cause and effect of this relationship. Even less is known about the mechanisms linking the two. Physical activity is a logical suspect, but no study has demonstrated its role. PURPOSE: This study was designed to examine the interrelationship between physical activity, obesity, and LBP. The specific aims were to determine if obesity is a risk factor for LBP in the U.S. population, measure the strength of any observed association, and evaluate the role of physical activity in modulating this association. STUDY DESIGN/SETTING: A cross-sectional U.S. population-based study. PATIENT SAMPLE: A cohort of 6,796 adults from the 2003 2004 National Health and Nutrition Examination Survey. OUTCOME MEASURES: Demographic information, an in-depth health questionnaire, physical examination details, and 7-day free-living physical activity monitoring using accelerometry (ActiGraph AM-7164; ActiGraph, Pensacola, FL, USA). METHODS: LBP status was determined by questionnaire response. Body mass index (BMI) was calculated during physical examination and divided here into four groups (normal weight <25, overweight 25-30, obese 31-35, and ultraobese 36+). Summary measures of physical activity were computed based on intensity cutoffs, percentile intensities, and bout. Demographics, social history, and comorbid health conditions were used to build adjusted weighted logistic regression models constructed using Akaike Information Criterion. All displayed estimates are significant at level <.05. No external funding was received to support this study. None of the authors report conflicts of interest directly related to the specific subject matter of this manuscript. RESULTS: In the U.S. population, the risk of low LBP increases in step with BMI from 2.9% for normal BMI (20-25) to 5.2% for overweight (26-30), 7.7% for obese (31-35), and 11.6% for ultraobese (36+). Smoking is consistently the strongest predictor of LBP across the BMI spectrum (odds ratio 1.6-2.9). Physical activity also modulates these risks. In the overall model, the best physical activity predictors of LBP are in the moderate and high intensity ranges with small effects (odds ratio 0.98 and 0.996 per standard deviation increase, respectively). When broken down by BMI, time spent in sedentary and moderate activity ranges demonstrate more robust influences on LBP status in the overweight, obese, and ultraobese groups. CONCLUSIONS: Increased BMI is a risk factor for back pain in Americans. More important, the role of physical activity in mitigating back pain risk is shown to be of greater consequence in the overweight and obese populations. PMID- 24239801 TI - Assessment of skeletal maturity in scoliosis patients to determine clinical management: a new classification scheme using distal radius and ulna radiographs. AB - BACKGROUND: Assessment of skeletal maturity in patients with adolescent idiopathic scoliosis (AIS) is important to guide clinical management. Understanding growth peak and cessation is crucial to determine clinical observational intervals, timing to initiate or end bracing therapy, and when to instrument and fuse. The commonly used clinical or radiologic methods to assess skeletal maturity are still deficient in predicting the growth peak and cessation among adolescents, and bone age is too complicated to apply. PURPOSE: To address these concerns, we describe a new distal radius and ulna (DRU) classification scheme to assess skeletal maturity. STUDY DESIGN: A prospective study. PATIENT SAMPLE: One hundred fifty young, female AIS patients with hand x-rays and no previous history of spine surgery from a single institute were assessed. OUTCOME MEASURES: Radius and ulna plain radiographs, and various anthropomorphic parameters were assessed. METHODS: We identified various stages of radius and ulna epiphysis maturity, which were graded as R1-R11 for the radius and U1-U9 for the ulna. The bone age, development of sexual characteristics, standing height, sitting height, arm span, radius length, and tibia length were studied prospectively at each stage of these epiphysis changes. RESULTS: Standing height, sitting height, and arm span growth were at their peak during stages R7 (mean, 11.4 years old) and U5 (mean, 11.0 years old). The long bone growths also demonstrated a common peak at R7 and U5. Cessation of height and arm span growth was noted after stages R10 (mean, 15.6 years old) and U9 (mean, 17.3 years old). CONCLUSIONS: The new DRU classification is a practical and easy-to-use scheme that can provide skeletal maturation status. This classification scheme provides close relationship with adolescent growth spurt and cessation of growth. This classification may have a tremendous utility in improving clinical-decision making in the conservative and operative management of scoliosis patients. PMID- 24239802 TI - Back pain's association with vertebral end-plate signal changes in sciatica. AB - BACKGROUND CONTEXT: Patients with sciatica frequently experience disabling back pain. One of the proposed causes for back pain is vertebral end-plate signal changes (VESC) as visualized by magnetic resonance imaging (MRI). PURPOSE: To report on VESC findings, changes of VESC findings over time, and the correlation between VESC and disabling back pain in patients with sciatica. STUDY DESIGN/SETTING: A randomized clinical trial with 1 year of follow-up. PATIENTS SAMPLE: Patients with 6 to 12 weeks of sciatica who participated in a multicenter, randomized clinical trial comparing an early surgery strategy with prolonged conservative care with surgery if needed. OUTCOME MEASURES: Patients were assessed by means of the 100-mm visual analog scale (VAS) for back pain (with 0 representing no pain and 100 the worst pain ever experienced) at baseline and 1 year. Disabling back pain was defined as a VAS score of at least 40 mm. METHODS: Patients underwent MRI both at baseline and after 1 year follow-up. Presence and change of VESC was correlated with disabling back pain using chi square tests and logistic regression analysis. RESULTS: At baseline, 39% of patients had disabling back pain. Of the patients with VESC at baseline, 40% had disabling back pain compared with 38% of the patients with no VESC (p=.67). The prevalence of type 1 VESC increased from 1% at baseline to 35% 1 year later in the surgical group compared with an increase from 3% to 11% in the conservative group. The prevalence of type 2 VESC decreased from 40% to 29% in the surgical group while remaining almost stable in the conservative group at 41%. The prevalence of disabling back pain at 1 year was 12% in patients with no VESC at 1 year, 16% in patients with type 1 VESC, 11% in patients with type 2 VESC, and 3% in patients with both types 1 and 2 VESC (p=.36). Undergoing surgery was associated with increase in the extent of VESC (odds ratio [OR], 8.6; 95% confidence interval [CI], 4.7-15.7; p<.001). Patients who showed an increase in the extent of VESC after 1 year did not significantly report more disabling back pain compared with patients who did not show any increase (OR, 1.2; 95% CI, 0.6 2.6; p=.61). CONCLUSION: In this study, undergoing surgery for sciatica was highly associated with the development of VESC after 1 year. However, in contrast with the intuitive feeling of spine specialists, those with and those without VESC reported disabling back pain in nearly the same proportion. Therefore, VESC does not seem to be responsible for disabling back pain in patients with sciatica. PMID- 24239803 TI - Comparative outcomes and cost-utility following surgical treatment of focal lumbar spinal stenosis compared with osteoarthritis of the hip or knee: part 2- estimated lifetime incremental cost-utility ratios. AB - BACKGROUND CONTEXT: Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) have been widely accepted as highly cost-effective procedures, spine surgery for the treatment of degenerative conditions does not share the same perception among stakeholders. In particular, the sustainability of the outcome and cost-effectiveness following lumbar spinal stenosis (LSS) surgery compared with THA/TKA remain uncertain. PURPOSE: The purpose of the study was to estimate the lifetime incremental cost-utility ratios for decompression and decompression with fusion for focal LSS versus THA and TKA for osteoarthritis (OA) from the perspective of the provincial health insurance system (predominantly from the hospital perspective) based on long-term health status data at a median of 5 years after surgical intervention. STUDY DESIGN/SETTING: An incremental cost-utility analysis from a hospital perspective was based on a single-center, retrospective longitudinal matched cohort study of prospectively collected outcomes and retrospectively collected costs. PATIENT SAMPLE: Patients who had undergone primary one- to two-level spinal decompression with or without fusion for focal LSS were compared with a matched cohort of patients who had undergone elective THA or TKA for primary OA. OUTCOME MEASURES: Outcome measures included incremental cost-utility ratio (ICUR) ($/quality adjusted life year [QALY]) determined using perioperative costs (direct and indirect) and Short Form 6D (SF-6D) utility scores converted from the SF-36. METHODS: Patient outcomes were collected using the SF-36 survey preoperatively and annually for a minimum of 5 years. Utility was modeled over the lifetime and QALYs were determined using the median 5-year health status data. The primary outcome measure, cost per QALY gained, was calculated by estimating the mean incremental lifetime costs and QALYs for each diagnosis group after discounting costs and QALYs at 3%. Sensitivity analyses adjusting for +25% primary and revision surgery cost, +25% revision rate, upper and lower confidence interval utility score, variable inpatient rehabilitation rate for THA/TKA, and discounting at 5% were conducted to determine factors affecting the value of each type of surgery. RESULTS: At a median of 5 years (4-7 years), follow-up and revision surgery data was attained for 85%-FLSS, 80%-THA, and 75%-THA of the cohorts. The 5-year ICURs were $21,702/QALY for THA; $28,595/QALY for TKA; $12,271/QALY for spinal decompression; and $35,897/QALY for spinal decompression with fusion. The estimated lifetime ICURs using the median 5-year follow-up data were $5,682/QALY for THA; $6,489/QALY for TKA; $2,994/QALY for spinal decompression; and $10,806/QALY for spinal decompression with fusion. The overall spine (decompression alone and decompression and fusion) ICUR was $5,617/QALY. The estimated best- and worst-case lifetime ICURs varied from $1,126/QALY for the best-case (spinal decompression) to $39,323/QALY for the worst case (spinal decompression with fusion). CONCLUSION: Surgical management of primary OA of the spine, hip, and knee results in durable cost-utility ratios that are well below accepted thresholds for cost-effectiveness. Despite a significantly higher revision rate, the overall surgical management of FLSS for those who have failed medical management results in similar median 5-year and lifetime cost-utility compared with those of THA and TKA for the treatment of OA from the limited perspective of a public health insurance system. PMID- 24239804 TI - Clinical outcomes following surgical management of coexistent cervical stenosis and multiple sclerosis: a cohort-controlled analysis. AB - BACKGROUND CONTEXT: The presentation of myelopathy in patients with the concomitant diagnosis of cervical stenosis (CS) and multiple sclerosis (MS) complicates both diagnosis and treatment because of the similarities of presentation and disease progression. There are only a few published case series that examine this unique patient population. PURPOSE: To define the demographic features and presenting symptoms of patients with both MS and CS and to investigate the immediate and long-term outcomes of surgery in patients with MS and CS. STUDY DESIGN/SETTING: Matched cohort-controlled retrospective review of 77 surgical patients in the MS group and 77 surgical patients in the control group. Outcome measures were immediate and long-term postoperative neck pain, radiculopathy, and myelopathy; Nurick Disability and modified Japanese Orthopaedic Association scores were collected as well. METHODS: Retrospective review was performed for all patients presenting at one institution between January 1996 and July 2011 with coexisting diagnoses of MS and CS who had presenting symptoms of myelopathy and who then underwent cervical decompression surgery. Each study patient was individually matched to a control patient of the same gender and age that did not have MS, but that did have cervical spondylotic myelopathy or myeloradiculopathy. Each control patient underwent the same surgical procedure within the same year. RESULTS: A total of 154 patients were reviewed, including 77 MS patients and 77 control patients, for an average follow up of 58 months and 49 months, respectively. Patients in the control group were more likely to have preoperative neck pain (78% vs. 47%; p=.0001) and preoperative radiculopathy (90% vs. 75%; p=.03) than their counterparts in the MS group. Patients in the MS group had a significantly lower rate of postoperative resolution of myelopathic symptoms in both the short-term (39% in the MS group did not improve vs. 23% in the control group; p=.04) and the long-term (44% in the MS group did not improve vs. 19% in the control group; p=.004). Preoperative myelopathy scores were worse for the MS cohort as compared with the control cohort (1.8 vs. 1.2 in the Nurick scale, p<.0001; 13.7 vs. 15.0 in the modified Japanese Orthopaedic Association scale, p=.002). This difference in scores became even greater at the last follow-up visit with Nurick scores of 2.4 versus 0.9 (p<.0001) and modified Japanese Orthopaedic Association scores of 16.3 versus 12.4 (p<.0001) for the MS and control patients, respectively. CONCLUSIONS: Myelopathic patients with coexisting MS and CS improve after surgery, although at a lower rate and to a lesser degree than those without MS. Therefore, surgery should be considered for these patients. MS patients should be informed that myelopathy symptoms are less likely to be alleviated completely or may only be alleviated temporarily because of progression of MS and that surgery can help alleviate neck pain and radicular symptoms. PMID- 24239805 TI - Reliability of computer-assisted lumbar intervertebral measurements using a novel vertebral motion analysis system. AB - BACKGROUND CONTEXT: Traditional methods for the evaluation of in vivo spine kinematics introduce significant measurement variability. Digital videofluoroscopic techniques coupled with computer-assisted measurements have been shown to reduce such error, as well as provide detailed information about spinal motion otherwise unobtainable by standard roentgenograms. Studies have evaluated the precision of computer-assisted fluoroscopic measurements; however, a formal clinical evaluation and comparison with manual methods is unavailable. Further, it is essential to establish reliability of novel measurements systems compared with standard techniques. PURPOSE: To determine the repeatability and reproducibility of sagittal lumbar intervertebral measurements using a new system for the evaluation of lumbar spine motion. STUDY DESIGN: Reliability evaluation of digitized manual versus computer-assisted measurements of the lumbar spine using motion sequences from a videofluoroscopic technique. PATIENT SAMPLE: A total of 205 intervertebral levels from 61 patients were retrospectively evaluated in this study. OUTCOME MEASURES: Coefficient of repeatability (CR), limits of agreement (LOA), intraclass correlation coefficient (ICC; type 3,1), and standard error of measurement. METHODS: Intervertebral rotations and translations (IVR and IVT) were each measured twice by three physicians using the KineGraph vertebral motion analysis (VMA) system and twice by three different physicians using a digitized manual technique. Each observer evaluated all images independently. Intra- and interobserver statistics were compiled based on the methods of Bland-Altman (CR, LOA) and Shrout-Fleiss (ICC, standard error of measurement). RESULTS: The VMA measurements demonstrated substantially more precision compared with the manual technique. Intraobserver measurements were the most reliable, with a CR of 1.53 (manual, 8.28) for IVR, and 2.20 (manual, 11.75) for IVT. The least reliable measurements were interobserver IVR and IVT, with a CR of 2.15 (manual, 9.88) and 3.90 (manual, 12.43), respectively. The ICCs and standard error results followed the same pattern. CONCLUSIONS: The VMA system markedly reduced variability of lumbar intervertebral measurements compared with a digitized manual analysis. Further, computer-assisted fluoroscopic imaging techniques demonstrate precision within the range of computer-assisted X-ray analysis techniques. PMID- 24239806 TI - Intrauterine metabolic programming alteration increased susceptibility to non alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring. AB - An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD. PMID- 24239807 TI - Antiviral signaling protein MITA acts as a tumor suppressor in breast cancer by regulating NF-kappaB induced cell death. AB - Emerging evidences suggest that chronic inflammation is one of the major causes of tumorigenesis. The role of inflammation in regulation of breast cancer progression is not well established. Recently Mediator of IRF3 Activation (MITA) protein has been identified that regulates NF-kappaB and IFN pathways. Role of MITA in the context of inflammation and cancer progression has not been investigated. In the current report, we studied the role of MITA in the regulation of cross talk between cell death and inflammation in breast cancer cells. The expression of MITA was significantly lower on in estrogen receptor (ER) positive breast cancer cells than ER negative cells. Similarly, it was significantly down regulated in tumor tissue as compared to the normal tissue. The overexpression of MITA in MCF-7 and T47D decreases the cell proliferation and increases the cell death by activation of caspases. MITA positively regulates NF kappaB transcription factor, which is essential for MITA induced cell death. The activation of NF-kappaB induces TNF-alpha production which further sensitizes MITA induced cell death by activation of death receptor pathway through capsase 8. MITA expression decreases the colony forming units and migration ability of MCF-7 cells. Thus, our finding suggests that MITA acts as a tumor suppressor which is down regulated during tumorigenesis providing survival advantage to tumor cell. PMID- 24239808 TI - Resistance reminders: Dieters reduce energy intake after exposure to diet congruent food images compared to control non-food images. AB - Dieters' long term goals to lose weight often fail in the short term due to hedonic temptations. Restrained eating coupled with disinhibition can lead to overconsumption when highly palatable foods are available. In contrast, it is predicted that exposure to diet-congruent food cues remind dieters of their long term diet goals and prompt short term regulation of food intake. To test this prediction, a between-subjects study involving female dieters (n=26) and non dieters (n=41) was conducted with brief exposure to diet-congruent or neutral non food images (23ms) before a tempting snack. Subsequent diet-cognitions using a lexical decision task and intake of tempting snacks were measured. Results showed that dieters exposed to diet-congruent images consumed less energy than dieters exposed to control images. In addition, high restrained high disinhibited participants reduced energy intake after exposure to diet-congruent compared to control images. There were no differences in dieters' reaction times to diet words across conditions in the lexical decision task. The results suggest that diet-congruent cues might act as effective reminders to limit intake in those most vulnerable to food temptations. Future research should examine the efficacy of such cues for longer term weight control. PMID- 24239809 TI - Cofractionation of HMGB proteins with histone dimers. AB - An effective and flexible method is presented that can be used to investigate cofractionation of groups of nuclear proteins. The method was used to analyze chromatin-related proteins, of which high-mobility group B (HMGB) proteins consistently cofractionated by cation-exchange chromatography with the histone dimer (H2A-H2B). This led to the hypothesis that the two form a complex, further suggested by gel filtration, in which the HMGBs with core histones eluted as a defined high-molecular-weight peak. A necessary requirement for further studying protein interactions is that the constituents are of the highest possible purity and the pure histone dimers and tetramers used in this study were derived from pure histone octamers with their native marks. There is a growing interest in protein-protein interactions and an increasing focus on protein-interaction domains: most frequently, pull-down assays are used to examine these. The technology presented here can provide an effective system that complements pull down assays. PMID- 24239810 TI - The recreational value of different winter conditions in Oslo forests: a choice experiment. AB - Cross-country skiing is important to many Norwegians as exercise and recreation during winter. The most heavily used areas for cross-country skiing are the forests near the capital city Oslo. Here, observed and predicted climate change lead to reduced snow days. A choice experiment estimates forest users' willingness to pay (WTP) for trips to the forest under different conditions: skiing conditions, bare ground, and wet snow not suitable for skiing. Snow conditions correlate with the highest WTP per trip, while the WTP for trips under bare conditions and wet snow is, respectively, 40 and 77% less. Expressed in terms of distance, the analysis indicates that the maximum willingness to travel (WTT) for the average trip is 45 km (each direction) for snow, 23 km for bare ground, while not significantly different from zero for wet snow. The large difference in value across different conditions suggests that climate change may reduce the recreational value for forest users considerably. PMID- 24239811 TI - Beyond regulations: industry voluntary ban in arsenic use. AB - Firms play a key role in pollution abatement and control by engaging in beyond compliance actions without the force of law in voluntary programs. This study examines the effectiveness of a bilateral voluntary agreement, one type of voluntary programs, negotiated between the U.S. Environmental Protection Agency (EPA) and the pressure-treated wood industry to phase-out the use of chromated copper arsenate (CCA), a poisonous arsenic compound. Arsenic is ranked number one on the EPA's priority list of hazardous substances. Unlike a majority of earlier studies on voluntary programs, dynamic panel estimation and structural break analysis show that while a technological innovation in semiconductors is associated with arsenic use increases, the CCA voluntary agreement is associated with a reduction in arsenic use to levels not seen since the 1920s. A voluntary ban in arsenic acid by pesticide manufacturers in the agriculture sector has also contributed to arsenic reductions. Furthermore, the results suggest that environmental activism has played a role in curbing arsenic use. Increasing stakeholder pressures, as measured by membership in the Sierra Club, improves voluntary agreement effectiveness. PMID- 24239813 TI - Enrichment and geo-accumulation of heavy metals and risk assessment of sediments of the Kurang Nallah--feeding tributary of the Rawal Lake Reservoir, Pakistan. AB - Heavy metal concentrations in sediments of the Kurang stream: a principal feeding tributary of the Rawal Lake Reservoir were investigated using enrichment factor (EF), geoaccumulation index (Igeo) and metal pollution index (MPI) to determine metal accumulation, distribution and its pollution status. Sediment samples were collected from twenty one sites during two year monitoring in pre- and post monsoon seasons (2007-2008). Heavy metal toxicity risk was assessed using Sediment Quality Guidelines (SQGs), effect range low/effect range median values (ERL/ERM), and threshold effect level/probable effect level (TEL/PEL). Greater mean concentrations of Ni, Mn and Pb were recorded in post-monsoon season whereas metal accumulation pattern in pre-monsoon season followed the order: Zn>Mn>Ni>Cr>Co>Cd>Pb>Cu>Li. Enrichment factor (EF) and geoaccumulation (Igeo) values showed that sediments were loaded with Cd, Zn, Ni and Mn. Comparison with uncontaminated background values showed higher concentrations of Cd, Zn and Ni than respective average shale values. Concentrations of Ni and Zn were above ERL values; however, Ni concentration exceeded the ERM values. Sediment contamination was attributed to anthropogenic and natural processes. The results can be used for effective management of fresh water hilly streams of Pakistan. PMID- 24239812 TI - Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging. AB - Can we reset, reprogram, rejuvenate, or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be manipulated further into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact and noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but essentially inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these 2 phenomena to rejuvenate over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states based on diverse epigenotypes in response to intrinsic or extrinsic environmental cues and genetic perturbations. We hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds and windows of plasticity and its robustness by molecular genetic and chemical epigenetic approaches, we have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during their embryonic and/or larval stages ("embryonic/larval senescence"). Subsequently, at least some of these mutant animals were found to show a shortened life span, whereas others would be expected to live longer into adulthood. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence related genes might also be involved in the early developmental process and its regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes, genotypes, and epigenotypes that can be linked to the senescence phenotype, which facilitates searching for the evolutionary and developmental origins of aging in vertebrates. PMID- 24239814 TI - Effective drinking water collaborations are not accidental: interagency relationships in the international water utility sector. AB - The role that deficient institutional relationships have played in aggravating drinking water incidents over the last 30 years has been identified in several inquiries of high profile drinking water safety events, peer-reviewed articles and media reports. These indicate that collaboration between water utilities and public health agencies (PHAs) during normal operations, and in emergencies, needs improvement. Here, critical elements of these interagency collaborations, that can be integrated within the corporate risk management structures of water utilities and PHAs alike, were identified using a grounded theory approach and 51 semi-structured interviews with utility and PHA staff. Core determinants of effective interagency relationships are discussed. Intentionally maintained functional relationships represent a key ingredient in assuring the delivery of safe, high quality drinking water. PMID- 24239815 TI - Assessing traffic and polycyclic aromatic hydrocarbon exposure in Montreal, Canada. AB - INTRODUCTION: The International Agency for Research on Cancer classifies specific polycyclic aromatic hydrocarbons (PAHs) as probable carcinogens. This study compares two PAH biomarkers and their relationship with geographic information system (GIS) based traffic density (a proxy of PAH exposure), and explores the determinants of the PAH biomarkers. METHODS: A cross-sectional study was conducted in Montreal with 200 volunteers (107 females and 93 males) ages 20 to 53 years. Data were collected by questionnaire, urine samples were used for biomarker analysis, and innovative GIS-based time- and distance-weighted traffic densities (TDWTD) were calculated for all locations of participants during the 48 h prior to urine collection. RESULTS: Detection rates of the two biomarkers were greater than 95%. Female participants had higher 1-OHP and 1-OHPG levels than males, and no relationship was detected between TDWTD in 48 h and the two PAH biomarkers. Biomarker levels were related to smoking more than one pack of cigarettes in the previous 48 h, and among non-smokers, barbecued meat consumption increased the level of urinary 1-OHP (exp beta: 1.45, 95% CI: 1.07 to 1.98). CONCLUSIONS: Both 1-OHP and 1-OHPG can be used to assess the relatively low PAH levels to which the general population is exposed. With the exception of smoking, the impact of PAH exposure factors on the biomarkers is relatively small in this study population. PMID- 24239816 TI - Sustainability appraisal tools for soil and groundwater remediation: how is the choice of remediation alternative influenced by different sets of sustainability indicators and tool structures? AB - The state-of-the-science in sustainability assessment of soil and groundwater remediation is evaluated with the application of four decision support systems (DSSs) to a large-scale brownfield revitalization case study. The DSSs were used to perform sustainability appraisals of four technically feasible remediation alternatives proposed for the site. The first stage of the review compares the scope of each tool's sustainability indicators, how these indicators are measured and how the tools differ in terms of standardization and weighting procedures. The second stage of the review compares the outputs from the tools and determines the key factors that result in differing results between tools. The evaluation of indicator sets and tool structures explains why the tools generate differing results. Not all crucial impact areas, as identified by sustainable remediation forums, are thoroughly considered by the tools, particularly with regard to the social and economic aspects of sustainability. Variations in boundary conditions defined between technologies, produce distorted environmental impact results, especially when in-situ and ex-situ technologies are compared. The review draws attention to the need for end users to be aware of which aspects of sustainability are considered, how the aspects are measured and how all aspects are ultimately balanced in the evaluation of potential remediation strategies. Existing tools can be improved by considering different technologies within the same boundary conditions and by expanding indicator sets to include indicators deemed to be relevant by remediation forums. PMID- 24239817 TI - Effects of over-winter green cover on soil solution nitrate concentrations beneath tillage land. AB - There is a growing need to reduce nitrogen losses from agricultural systems to increase food production while reducing negative environmental impacts. The efficacy of vegetation cover for reducing nitrate leaching in tillage systems during fallow periods has been widely investigated. Nitrate leaching reductions by natural regeneration (i.e. growth of weeds and crop volunteers) have been investigated to a lesser extent than reductions by planted cover crops. This study compares the efficacy of natural regeneration and a sown cover crop (mustard) relative to no vegetative cover under both a reduced tillage system and conventional plough-based system as potential mitigation measures for reducing over-winter soil solution nitrate concentrations. The study was conducted over three winter fallow seasons on well drained soil, highly susceptible to leaching, under temperate maritime climatic conditions. Mustard cover crop under both reduced tillage and conventional ploughing was observed to be an effective measure for significantly reducing nitrate concentrations. Natural regeneration under reduced tillage was found to significantly reduce the soil solution nitrate concentrations. This was not the case for the natural regeneration under conventional ploughing. The improved efficacy of natural regeneration under reduced tillage could be a consequence of potential stimulation of seedling germination by the autumn reduced tillage practices and improved over-winter plant growth. There was no significant effect of tillage practices on nitrate concentrations. This study shows that over winter covers of mustard and natural regeneration, under reduced tillage, are effective measures for reducing nitrate concentrations in free draining temperate soils. PMID- 24239818 TI - Assessing atmospheric particulate matter distribution based on Saturation Isothermal Remanent Magnetization of herbaceous and tree leaves in a tropical urban environment. AB - Particulate matter (PM) emissions, and the associated human health risks, are likely to continue increasing in urban environments of developing countries like Abidjan (Ivory Cost). This study evaluated the potential of leaves of several herbaceous and tree species as bioindicators of urban particulate matter pollution, and its variation over different land use classes, in a tropical area. Four species well distributed (presence frequencies >90%) over all land use classes, easy to harvest and whose leaves are wide enough to be easily scanned were selected, i.e.: Amaranthus spinosus (Amaranthaceae), Eleusine indica (Poaceae), Panicum maximum (Poaceae) and Ficus benjamina (Moraceae). Leaf sampling of these species was carried out at 3 distances from the road and at 3 height levels. Traffic density was also noted and finally biomagnetic parameters of these leaves were determined. Results showed that Saturation Isothermal Remanent Magnetization (SIRM) of leaves was at least 4 times higher (27.5*10( 6)A) in the vicinity of main roads and industrial areas than in parks and residential areas. The main potential sources of PM pollution were motor vehicles and industries. The slightly hairy leaves of the herbaceous plant A. spinosus and the waxy leaves of the tree F. benjamina showed the highest SIRM (25*10(-6)A). Leaf SIRM increased with distance to road (R(2)>0.40) and declined with sampling height (R(2)=0.17). The distance between 0 and 5m from the road seemed to be the most vulnerable in terms of PM pollution. This study has showed that leaf SIRM of herbaceous and tree species can be used to assess PM exposure in tropical urban environments. PMID- 24239819 TI - Metagenomic analysis reveals potential biodegradation pathways of persistent pesticides in freshwater and marine sediments. AB - The abundance and diversity of biodegradation genes (BDGs) and potential degradation pathways of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), and atrazine (ATZ) in freshwater and marine sediments were investigated by metagenomic analysis using 6 datasets (16Gb in total). The datasets were derived using Illumina high-throughput sequencing and were based on BLAST against self-established databases of BDGs, DDT degradation genes (DDGs), HCH degradation genes (HDGs), and ATZ degradation genes (ADGs). The results showed that the abundance and diversity of BDGs, DDGs, HDGs, and ADGs varied with sample source and locations. The lip and mnp genes, which encode for peroxidase, and the carA gene, which encodes for laccase, were detected as the dominant genes for degradation of organic pollutants. The hdt, hdg, and atzB genes, which encode for hydratase, dehalogenase, and ethylaminohydrolase, were found to be the most abundant genes involved in DDT, HCH, and ATZ degradation, respectively. The identified 69 genera capable of degrading organic pollutants were mostly affiliated with Proteobacteria (49.3%) and Actinobacteria (21.7%). Four genera, including Plesiocystis, Anaerolinea, Jannaschia, and Mycobacterium, were the major biodegradation populations in all sediments. In this study, the nearly complete biodegradation pathways of DDT and ATZ were found, and the partial degradation pathway of HCH was detected in all sediments. PMID- 24239820 TI - Accumulation of uranium by aquatic plants in field conditions: prospects for phytoremediation. AB - A study was undertaken to determine Uranium concentrations in water and aquatic plants in the uraniferous region of Beiras, Central Portugal. Samples were collected from running water (n=200) at places where aquatic species were observed. Plant samples were collected from 28 species of submerged, free floating and rooted emergent plants including 2 bryophytes and 1 pteridophyte. Uranium concentrations in surface waters ranged from 0.23 to 1,217 MUg L(-1). The aquatic plant species studied, including several previously untested species, exhibited the ability to accumulate U in concentrations many times that of the ambient water. In general submerged plants exhibited higher U content followed by rooted emergent and free floating species. The highest U concentrations were observed in the bryophyte Fontinalis antipyretica (up to 4,979 mg kg(-1)) followed by Callitriche stagnalis (1963mgkg(-1)), Callitriche hamulata (379 mg kg(-1)), Ranunculus peltatus subsp. saniculifolius (243 mg kg(-1)), Callitriche lusitanica (218 mg kg(-1)), and Ranunculus trichophyllus (65.8 mg kg(-1)). In two out of three rooted emergent species U seemed to be preferentially partitioned in rhizome/roots with highest rhizome U content recorded in Typha latifolia (380 mg kg(-1)). Among the free-floating species, the highest U content (42.5 mg kg(-1)) was seen in Lemna minor. The bryophyte F. antipyretica and Callitrichaceae members seem to be promising candidates for the development of phytofiltration methodologies based on U accumulation, abundance and biomass production. PMID- 24239821 TI - The effect of temperature gradients on endocrine signaling and antioxidant gene expression during Chironomus riparius development. AB - Temperature is one of the most important environmental factors affecting the biological processes of aquatic species. To investigate the potential effects of temperature on the developmental processes of aquatic invertebrates, we analyzed biological and molecular transcriptional responses during Chironomus riparius development, including five stages spanning from embryo to adult stages. We assessed the temperature change-induced reduction of survival rate, changes in biological development including the male:female ratio in emerged adults, the success rates of pupation and emergence, and the developmental timing of pupation and emergence. The increased temperature induced expression of endocrine signaling genes, such as the ecdysone receptor, ultraspiracle (ortholog of the RXR), and the estrogen-related receptor in the fourth-instar larval and pupal stages of C. riparius development. Altered temperature also affected the activity of antioxidant genes, including catalase, peroxidase, glutathione peroxidase, and superoxide dismutase during the fourth-instar larval to adult stages of C. riparius development, as a result of altered development. Increased temperature during the fourth-instar larval stage increased oxidative stress in pupae and adults. Responses of antioxidant genes to increased temperature occurred in a developmental stage-dependent manner. However, reduced temperature did not induce the expression of antioxidant genes in a developmental stage-dependent manner, although it did induce oxidative stress during C. riparius development. Increased temperature also caused greater toxicity of di-ethylhexyl phthalate (DEHP) in fourth-instar larvae. Our findings suggest that altered temperatures may disturb the invertebrate hormone system and developmental processes by inducing oxidative stress in aquatic environments. PMID- 24239822 TI - Responses of wild small mammals to arsenic pollution at a partially remediated mining site in Southern France. AB - Partial remediation actions at a former gold mine in Southern France led to a mosaic of contaminated and rehabilitated zones. In this study, the distribution of arsenic and its potential adverse effects on small mammals were investigated. The effectiveness of remediation for reducing the transfer of this element into wildlife was also discussed. Arsenic levels were measured in the soil and in the stomach contents, livers, kidneys, and lungs of four small mammal species (the wood mouse (Apodemus sylvaticus), the Algerian mouse (Mus spretus), the common vole (Microtus arvalis), and the greater white-toothed shrew (Crocidura russula)). The animals were caught at the former extraction site, in zones with three different levels of remediation treatments, and at a control site. Arsenic concentrations in the soil were highly spatially heterogeneous (ranging from 29 to 18,900 MUg g(-1)). Despite the decrease in arsenic concentrations in the remediated soils, both wood mice and Algerian mice experienced higher oral exposure to arsenic in remediated zones than in the control area. The accumulated arsenic in their organs showed higher intra-zonal variability than the arsenic distribution in the soil, suggesting that, in addition to remediation processes, other variables can help explain arsenic transfer to wildlife, such as the habitat and diet preferences of the animals or their mobility. A weak but significant correlation between arsenic concentration and body condition was observed, and weak relationships between the liver/kidney/lung mass and arsenic levels were also detected, suggesting possible histological alterations. PMID- 24239823 TI - Eggshell thinning of osprey (Pandion haliaetus) breeding in Sweden and its significance for egg breakage and breeding outcome. AB - In the middle of the 1960s low reproductive rate was found in several osprey (Pandion haliaetus) nests in Sweden. Therefore a project was started to investigate the production and to collect unhatched eggs and shell fragments in different regions of Sweden during 1971-2008. Measurements of osprey eggs from museum collections from 1840 to 1970 were included to study long-term changes in shell thickness. In total, eggshell thickness of whole eggs from 666 clutches and of shell fragments from 693 nests was measured. The thinnest shell fragments were recorded in 1973 (mean for 71 clutches: 0.438 mm), minus 15.0% compared to thickness of unaffected eggs before 1946 (0.515 mm). After 1973, shell thickness increased to reach background levels in 2003 (0.515 mm). Thus, it took 30 years to reach full thickness again. From the start of the decrease it took more than 50 years to reach unaffected conditions. The number of whole eggs remaining intact in the nest throughout incubation was reduced when shell thickness decreased. Great loss of eggs due to breakage seems to occur when the mean shell thickness in the clutch was below 0.40 mm. In 1971-1973, when shell thinning was most pronounced, the average thickness of shell fragments was 0.366 mm in nests with 0 intact eggs (minus 29% compared to the pre-1946 background value); 0.393 mm (minus 24%) in nests with 1 intact egg; 0.431 mm (minus 16%) in nests with 2 intact eggs and 0.450 mm (minus 12%) in nests with 3 intact eggs. Differences in thickness were significant for 1 versus 2 intact eggs, 2 vs. 3 intact eggs and for 0+1 vs. 2+3 intact eggs. Actual data from the period 1971-73 shows a decline in the production of young (4-5 weeks) of some 15% (0.25 young per nest). PMID- 24239824 TI - Feral finfish, and their relationships with sediments and seawater, as a tool for risk assessment of PAHs in chronically polluted environments. AB - An integrated study has been carried out of the fate and effects of PAHs in fish living in a chronically polluted environment. Total PAH concentrations in different target organs (muscle, liver and gills), have been determined in five species of feral fish and possible histopathological effects and correlations of all these values with concentrations found in sediments and water column have been studied in two of these species. The Potency Equivalent Concentrations and Screening values (SVs), the Biota-to-sediment accumulation factors (BSAFs) and the Toxic Potency Assessment (TEQ) of sediment for fish have been calculated. Results show that levels found in target organs, the TEQs of sediment calculated for fish related to the SVs for fish consumption are of special concern. However, the index of pathologies shows a relatively low impact of PAHs on fish health. The use of feral finfish in risk assessment for PAHs in chronically polluted environments has been proved to be a useful tool to complement environmental diagnoses and improve their accuracy. This approach combines the measurement of total concentrations in different target organs of several appropriate species, the study of histopathological effects, and correlations between all these results and the concentrations found in associated sediments and column water. PMID- 24239825 TI - Metabolic biotransformation half-lives in fish: QSAR modeling and consensus analysis. AB - Bioaccumulation in fish is a function of competing rates of chemical uptake and elimination. For hydrophobic organic chemicals bioconcentration, bioaccumulation and biomagnification potential are high and the biotransformation rate constant is a key parameter. Few measured biotransformation rate constant data are available compared to the number of chemicals that are being evaluated for bioaccumulation hazard and for exposure and risk assessment. Three new Quantitative Structure-Activity Relationships (QSARs) for predicting whole body biotransformation half-lives (HLN) in fish were developed and validated using theoretical molecular descriptors that seek to capture structural characteristics of the whole molecule and three data set splitting schemes. The new QSARs were developed using a minimal number of theoretical descriptors (n=9) and compared to existing QSARs developed using fragment contribution methods that include up to 59 descriptors. The predictive statistics of the models are similar thus further corroborating the predictive performance of the different QSARs; Q(2)ext ranges from 0.75 to 0.77, CCCext ranges from 0.86 to 0.87, RMSE in prediction ranges from 0.56 to 0.58. The new QSARs provide additional mechanistic insights into the biotransformation capacity of organic chemicals in fish by including whole molecule descriptors and they also include information on the domain of applicability for the chemical of interest. Advantages of consensus modeling for improving overall prediction and minimizing false negative errors in chemical screening assessments, for identifying potential sources of residual error in the empirical HLN database, and for identifying structural features that are not well represented in the HLN dataset to prioritize future testing needs are illustrated. PMID- 24239826 TI - Concentrations and potential health hazards of organochlorine pesticides in (shallow) groundwater of Taihu Lake region, China. AB - A total of 27 shallow groundwater samples were collected from the Taihu Lake region (TLR), to determine the concentrations of 14 organochlorine pesticide (OCP) species, identify their possible sources, and estimate health risk of drinking the shallow groundwater. All OCP species occurred in the shallow groundwater of TLR with high detection frequency except p, p' dichlorodiphenyldichlorothane (p, p'-DDD) and p, p' dichlorodiphenyltrichloroethane (p, p'-DDT). DDTs and hexachlorocyclohexanes (HCHs) were the dominant OCP contaminants in the shallow groundwater of TLR, and they account for 44.2% total OCPs. The low alpha-HCH/gamma-HCH ratio, high beta HCH/(alpha+gamma)-HCH ratio and beta-HCH being the dominant HCH isomers for the majority of samples suggest that the HCHs were mainly from the historical use of lindane after a period of degradation. p, p'-DDE being the dominant DDT metabolite for all the samples indicated that the DDTs were mainly from the historical residues. Compositional analysis also suggested that there were fresh input sources of heptachlors, aldrins and endrins in addition to the historical residues. Correlation analysis indicated the hexachlorobenzene (HCB) impurity in the shallow groundwater of TLR was likely from the historical application of lindane and technical HCH (a mixture of HCH isomers that is produced by photochlorination of benzene). Carcinogenic risk values for alpha-HCH, heptachlor, heptachlor epoxide, aldrins and dieldrin in the shallow groundwater in majority area of TLR were found to be >10(-6), posing a potentially serious cancer risk to those dependant on shallow groundwater for drinking water. PMID- 24239827 TI - Impact of secondary treatment types and sludge handling processes on estrogen concentration in wastewater sludge. AB - Endocrine-disrupting compounds (EDCs), such as estrogen, are known to be present in the aquatic environment at concentrations that negatively affect fish and other wildlife. Wastewater treatment plants (WWTPs) are major contributors of EDCs into the environment. EDCs are released via effluent discharge and land application of biosolids. Estrogen removal in WWTPs has been studied in the aqueous phase; however, few researchers have determined estrogen concentration in sludge. This study focuses on estrogen concentration in wastewater sludge as a result of secondary treatment types and sludge handling processes. Grab samples were collected before and after multiple treatment steps at two WWTPs receiving wastewater from the same city. The samples were centrifuged into aqueous and solid phases and then processed using solid phase extraction. Combined natural estrogens (estrone, estradiol and estriol) were measured using an enzyme-linked immunosorbent assay (ELISA) purchased from a manufacturer. Results confirmed that activated sludge treatments demonstrate greater estrogen removal compared to trickling filters and mass concentration of estrogen was measured for the first time on trickling filter solids. Physical and mechanical sludge treatment processes, such as gravity thickeners and centrifuges, did not significantly affect estrogen removal based on mass balance calculations. Dissolved air flotation thickening demonstrated a slight decrease in estrogen concentration, while anaerobic digestion resulted in increased mass concentration of estrogen on the sludge and a high estrogen concentration in the supernatant. Although there are no state or federally mandated discharge effluent standards or sludge application standards for estrogen, implications from this study are that trickling filters would need to be exchanged for activated sludge treatment or followed by an aeration basin in order to improve estrogen removal. Also, anaerobic digestion may need to be replaced with aerobic digestion for sludge that is intended for land application. PMID- 24239828 TI - Variance-based sensitivity analysis for wastewater treatment plant modelling. AB - Global sensitivity analysis (GSA) is a valuable tool to support the use of mathematical models that characterise technical or natural systems. In the field of wastewater modelling, most of the recent applications of GSA use either regression-based methods, which require close to linear relationships between the model outputs and model factors, or screening methods, which only yield qualitative results. However, due to the characteristics of membrane bioreactors (MBR) (non-linear kinetics, complexity, etc.) there is an interest to adequately quantify the effects of non-linearity and interactions. This can be achieved with variance-based sensitivity analysis methods. In this paper, the Extended Fourier Amplitude Sensitivity Testing (Extended-FAST) method is applied to an integrated activated sludge model (ASM2d) for an MBR system including microbial product formation and physical separation processes. Twenty-one model outputs located throughout the different sections of the bioreactor and 79 model factors are considered. Significant interactions among the model factors are found. Contrary to previous GSA studies for ASM models, we find the relationship between variables and factors to be non-linear and non-additive. By analysing the pattern of the variance decomposition along the plant, the model factors having the highest variance contributions were identified. This study demonstrates the usefulness of variance-based methods in membrane bioreactor modelling where, due to the presence of membranes and different operating conditions than those typically found in conventional activated sludge systems, several highly non linear effects are present. Further, the obtained results highlight the relevant role played by the modelling approach for MBR taking into account simultaneously biological and physical processes. PMID- 24239829 TI - Field dissipation and risk assessment of typical personal care products TCC, TCS, AHTN and HHCB in biosolid-amended soils. AB - The antimicrobial agents triclocarban (TCC) and triclosan (TCS) and synthetic musks AHTN (Tonalide) and HHCB (Galaxolide) are widely used in many personal care products. These compounds may release into the soil environment through biosolid application to agricultural land and potentially affect soil organisms. This paper aimed to investigate accumulation, dissipation and potential risks of TCC, TCS, AHTN and HHCB in biosolid-amended soils of the three field trial sites (Zhejiang, Hunan and Shandong) with three treatments (CK: control without biosolid application, T1: single biosolid application, T2: repeated biosolid application every year). The one-year monitoring results showed that biosolids application could lead to accumulation of these four chemicals in the biosolid amended soils, with the residual concentrations in the following order: TCC>TCS>AHTN>HHCB. Dissipation of TCC, TCS, AHTN and HHCB in the biosolid-amended soils followed the first-order kinetics model. Half-lives for TCC, TCS, AHTN and HHCB under the field conditions of Shandong site were 191, 258, 336 and 900 days for T1, and 51, 106, 159 and 83 days for T2, respectively. Repeated applications of biosolid led to accumulation of these personal care products and result in higher ecological risks. Based on the residual levels in the trial sites and limited toxicity data, high risks to soil organisms are expected for TCC and TCS, while low-medium risks for AHTN and HHCB. PMID- 24239830 TI - Four-year advanced monitoring program of polar pesticides in groundwater of Catalonia (NE-Spain). AB - Pesticide contamination of groundwater is of paramount importance because it is the most sensitive and the largest body of freshwater in the European Union. In this paper, an isotopic dilution method based on on-line solid phase extraction liquid chromatography (electrospray)-tandem mass spectrometry (SPE-LC(ESI)-MS/MS) was used for the analysis of 22 pesticides in groundwater. Results were evaluated from monitoring 112 wells and piezometers coming from 29 different aquifers located in 18 ground water bodies (GWBs), from Catalonia, Spain, for 4 years as part of the surveillance and operational monitoring programs conducted by the Catalan Water Agency. The analytical method developed allows the determination of the target pesticides (6 triazines, 4 phenylureas, 4 organophosphorous, 1 anilide, 2 chloroacetanilides, 1 thiocarbamate, and 4 acid herbicides) in groundwater with good sensitivity (limits of detection <5 ng/L), accuracy (relative recoveries between 85 and 116%, except for molinate), and repeatability (RSD<23%), and in a fully automated way. The most ubiquitous compounds were simazine, atrazine, desethylatrazine and diuron. Direct relation between frequency of detection of each target compound and Groundwater Ubiquity Score index (GUS index) is observed. Desethylatrazine and deisopropylatrazine, metabolites of atrazine and simazine, respectively, presented the highest mean concentrations. Compounds detected in less than 5% of the samples were cyanazine, molinate, fenitrothion and mecoprop. According to the Directive 2006/118/EC, 13 pesticides have individual values above the requested limits (desethylatrazine, atrazine and terbuthylazine lead the list) and 14 samples have total pesticide levels above 500 ng/L. The GWB with the highest levels of total pesticides is located in Lleida (NE-Spain), with 9 samples showing total pesticide levels above 500 ng/L. Several factors such as regulation of the use of pesticides, type of activities in the area, and irrigation were discussed in relation to the observed levels of pesticides. PMID- 24239831 TI - Towards fabrication of 3D printed medical devices to prevent biofilm formation. AB - The use of three-dimensional (3D) printing technologies is transforming the way that materials are turned into functional devices. We demonstrate in the current study the incorporation of anti-microbial nitrofurantoin in a polymer carrier material and subsequent 3D printing of a model structure, which resulted in an inhibition of biofilm colonization. The approach taken is very promising and can open up new avenues to manufacture functional medical devices in the future. PMID- 24239832 TI - Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: effects of concentration, thermodynamic activity and skin hydration. AB - The goal of these studies was to measure and interpret the skin permeability characteristics of 2-hydroxypropyl acrylate (HPA) as a model compound that is completely miscible with water. METHODS: In vitro permeation from HPA-H2O binary mixtures through human epidermis and silicone membranes was measured. Thermodynamic activities of HPA and H2O in these mixtures were determined. Permeation was also measured through epidermis and silicone from donor solutions with constant HPA activity but different H2O activities. Water uptake into desiccated human stratum corneum (SC) equilibrated with HPA-H2O mixtures was determined. RESULTS: Steady-state flux of HPA through silicone was a linear function of HPA activity but not HPA concentration. For epidermis on the other hand, flux increased with HPA activity only for HPA activities <= 0.35. At constant HPA activity, flux decreased 4.5-fold as water activity decreased from 1 to 0.8. Incubation of SC with HPA-H2O mixtures resulted in substantial changes in SC water content, dependent on the water activity of the mixture and consistent with measured SC water sorption data. CONCLUSIONS: These experiments provide unequivocal evidence of a substantial increase in epidermal barrier function resulting from SC dehydration. Dehydration-related alterations in the SC appear responsible for the observed flux characteristics. PMID- 24239833 TI - Effective siRNA delivery to inflamed primary vascular endothelial cells by anti-E selectin and anti-VCAM-1 PEGylated SAINT-based lipoplexes. AB - The endothelium represents an attractive therapeutic target due to its pivotal role in many diseases including chronic inflammation and cancer. Small interfering RNAs (siRNAs) specifically interfere with the expression of target genes and are considered an important new class of therapeutics. However, due to their size and charge, siRNAs do not spontaneously enter unperturbed endothelial cells (EC). To overcome this problem, we developed novel lipoplexes for siRNA delivery that are based on the cationic amphiphilic lipid SAINT-C18. Antibodies recognizing disease induced cell adhesion molecules were employed to create cell specificity resulting in so-called antibody-SAINTargs. To improve particle stability, antibody-SAINTargs were further optimized for EC-specific siRNA mediated gene silencing by addition of polyethylene glycol (PEG). Although PEGylated antibody-SAINTargs maintained specificity, they lost their siRNA delivery capacity. Coupling of antibodies to the distal end of PEG (so-called antibody-SAINTPEGargs), resulted in anti-E-selectin- and anti-vascular cell adhesion molecule (VCAM)-1-SAINTPEGarg that preserved their antigen recognition and their capability to specifically deliver siRNA into inflammation-activated primary endothelial cells. The enhanced uptake of siRNA by antibody-SAINTPEGargs was followed by improved silencing of the target gene VE-cadherin, demonstrating that antibody-SAINTPEGargs were capable of functionally delivering siRNA into primary endothelial cells originating from different vascular beds. In conclusion, the newly developed, physicochemically stable, and EC-specific siRNA carrying antibody-SAINTPEGargs selectively down-regulate target genes in primary endothelial cells that are generally difficult to transfect. PMID- 24239834 TI - Interaction between morin and AOT reversed micelles--studies with UV-vis at 25 degrees C. AB - The precise measurements of morin absorbance in presence of surfactant/solvent/water systems at 25 degrees C by UV-vis technique are reported. The surfactant used in presented study was sodium bis(2-ethylhexyl) sulfosuccinate called Aerosol-OT or AOT. The solvents selected were: ethanol, ethylene glycol, and n-decanol. The concentrations of AOT were varied between 0.001 and 0.4 mol/kg. Morin concentration in quvette during UV-vis registration was not equals in all solvent because of its different solubility and absorption intensity depending on the solvent. Water concentration in the studied systems was defined by R parameter according to relation: R=[H2O]/[AOT] and was equal 0, 30 and 40 in ethanol; 0, 10, 20 and 30 in ethylene glycol and 0, 10, 20, 30, and 40 in n-decanol. In presented work a Nernstian distribution of morin between the organic and micellar phases was assumed. The intensity of morin absorbance as a function of AOT concentration was analyzed. Using Non-linear Regression Procedure (NLREG) morin binding constant (K' [mol/kg]), and morin distribution constant (K) between organic phase and AOT micellar phase have been calculated. The experimental results have shown a significant influence of solvent, surfactant and water presence on morin UV-vis spectrum. Calculated data pointed out on different transfer of morin molecules from the organic to micellar phase depending on the solvent. Moreover, results of calculations indicate on competition between morin and water molecules interacting with AOT polar heads. Morin molecules privileged location in AOT reversed micelles strongly depends on the solvent. In case of systems with ethylene glycol as solvent is possible morin molecules location in polar cores of AOT reversed micelles as results of strong interaction between AOT polar heads and morin hydroxyl groups, whereas in case of ethanol and n-decanol morin molecules are located in palisade layer. PMID- 24239835 TI - Lipid-like trifunctional block copolymers of ethylene oxide and propylene oxide: effective and cytocompatible modulators of intracellular drug delivery. AB - A new glycerol-based trifunctional block copolymer (TBC) of propylene oxide and ethylene oxide and its conjugate with succinic acid (TBC-SA) were studied as a drug delivery system and compared with Pluronic L61. TBCs have multiple effects on the plasma membrane of human cells, e.g. increasing its fluidity and ion permeability, inhibiting ATPase activity of efflux transporter P-glycoprotein through reversible membrane destabilization. Such membrane-modulating properties attributed to the unimer form of copolymers increase in the order Pluronic L61?TBC56days post-injection, while the appearance of anti-HBs antibody in the serum was only found among <30% of female C57BL/6 mice injected with pCS-HBV1.3. Moreover, HBcAg and HBV DNA were also detected in the liver of HDI mice. Compared with previous AAV-backbone based HBV replicon DNA transfer, we found that the HDI transfer with the lentiviral vector-based HBV replicon (pCS HBV1.3) in this study resulted in a significantly higher level of HBV DNA transfer in the liver and longer persistence of HBV DNA and antigenaemia in the serum. Furthermore, we also showed that immunization of HBV replicon transfer mice with the novel HBSS1-based vaccines was able to overcome tolerance against HBV in mice and induces robust immunity (humoral as well as T-cell responses), followed by the clearance of the HBV viremia. We concluded that lentiviral backbone-based transfer vectors more readily establish persistent HBV infection in mouse models via HDI, providing a new tool useful for the study of HBV infection and immune-based therapies. PMID- 24239873 TI - Presence of hypogammaglobulinemia in patients with severe sepsis, septic shock, and SIRS is associated with increased mortality. PMID- 24239874 TI - LC-MS/MS characterization of combined glycogenin-1 and glycogenin-2 enzymatic activities reveals their self-glucosylation preferences. AB - Glycogen synthesis is initiated by self-glucosylation of the glycosyltransferases glycogenin-1 and -2 that, in the presence of UDP-glucose, form both the first glucose-O-tyrosine linkage, and then stepwise add a series of alpha1,4-linked glucoses to a growing chain of variable length. Glycogen-1 and -2 coexist in liver glycogen preparations where the proteins are known to form homodimers, and they also have been shown to interact with each other. In order to study how glycogenin-1 and -2 interactions may influence each other's glucosylations we setup a cell-free expression system for in vitro production and glucosylation of glycogenin-1 and -2 in various combinations, and used a mass spectrometry based workflow for the characterization and quantitation of tryptic glycopeptides originating from glycogenin-1 and -2. The analysis revealed that the self glucosylation endpoint was the incorporation of 4-8 glucose units on Tyr 195 of glycogenin-1, but only 0-4 glucose units on Tyr-228 of glycogenin-2. The glucosylation of glycogenin-2 was enhanced to 2-4 glucose units by the co presence of enzymatically active glycogenin-1. Glycogenin-2 was, however, unable to glucosylate inactive glycogenin-1, at least not an enzymatically inactivated Thr83Met glycogenin-1 mutant, recently identified in a patient with severe glycogen depletion. PMID- 24239875 TI - A simple breath sampling method in intubated and mechanically ventilated critically ill patients. AB - Volatile organic compounds (VOCs) in breath may serve as biomarkers of pulmonary infection or inflammation. We developed and validated a new breath sampling method for VOC analysis in ventilated patients. Breath was collected from the ventilatory circuit using cheap disposables. VOCs were identified by gas chromatography and mass-spectrometry (GC-MS) at various minute volumes during ventilation of an artificial lung (in vitro) and ventilated patients (in vivo). Sixty-four VOCs emendated from the ventilator and tubing. Their concentrations had an inverse correlation with minute volume in in vitro experiments (median correlation coefficient: -0.61 [25-75th percentile: -0.66 to -0.43]). Forty-four of these "ventilator-associated VOCs" were also observed in vivo, without correlations with minute volume. In vivo experiments showed that only positive end-expiratory pressure influenced the concentration of breath VOCs. The sampling method was highly reproducible (median intra-class correlation 0.95 [25-75th percentile: 0.87-0.97]). In conclusion, a novel, simple and repeatable sampling method was developed and validated for capturing exhaled VOCs in ventilated patients, which could allow for large-scale breath analysis in clinical studies. PMID- 24239876 TI - Role of hydrogen sulfide in secondary neuronal injury. AB - In acute neuronal insult events, such as stroke, traumatic brain injury, and spinal cord injury, pathological processes of secondary neuronal injury play a key role in the severity of insult and clinical prognosis. Along with nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is regarded as the third gasotransmitter and endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. The endogenous level of H2S in the brain is significantly higher than that in peripheral tissues, and is mainly formed by cystathionine beta-synthase (CBS) in astrocytes and released in response to neuronal excitation. The mechanism of secondary neuronal injury exacerbating the damage caused by the initial insult includes microcirculation failure, glutamate mediated excitotoxicity, oxidative stress, inflammatory responses, neuronal apoptosis and calcium overload. H2S dilates cerebral vessels by activating smooth muscle cell plasma membrane ATP-sensitive K channels (KATP channels). This modification occurs on specific cysteine residues of the KATP channel proteins which are S-sulfhydrated. H2S counteracts glutamate-mediated excitotoxicity by inducing astrocytes to intake more glutamate from the extracellular space and thus increasing glutathione in neurons. In addition, H2S protects neurons from secondary neuronal injury by functioning as an anti-oxidant, anti-inflammatory and anti-apoptotic mediator. However, there are still some reports suggest that H2S elevates neuronal Ca(2+) concentration and may contribute to the formation of calcium overload in secondary neuronal injury. H2S also elicits calcium waves in primary cultures of astrocytes and may mediate signals between neurons and glia. Consequently, further exploration of the molecular mechanisms of H2S in secondary neuronal injury will provide important insights into its potential therapeutic uses for the treatment of acute neuronal insult events. PMID- 24239877 TI - beta-xylosidases and alpha-L-arabinofuranosidases: accessory enzymes for arabinoxylan degradation. AB - Arabinoxylan (AX) is among the most abundant hemicelluloses on earth and one of the major components of feedstocks that are currently investigated as a source for advanced biofuels. As global research into these sustainable biofuels is increasing, scientific knowledge about the enzymatic breakdown of AX advanced significantly over the last decade. This review focuses on the exo-acting AX hydrolases, such as alpha-arabinofuranosidases and beta-xylosidases. It aims to provide a comprehensive overview of the diverse substrate specificities and corresponding structural features found in the different glycoside hydrolase families. A careful review of the available literature reveals a marked difference in activity between synthetically labeled and naturally occurring substrates, often leading to erroneous enzymatic annotations. Therefore, special attention is given to enzymes with experimental evidence on the hydrolysis of natural polymers. PMID- 24239878 TI - Mommy is only happy! Dutch mothers' realisation of speech sounds in infant directed speech expresses emotion, not didactic intent. AB - Exaggeration of the vowel space in infant-directed speech (IDS) is well documented for English, but not consistently replicated in other languages or for other speech-sound contrasts. A second attested, but less discussed, pattern of change in IDS is an overall rise of the formant frequencies, which may reflect an affective speaking style. The present study investigates longitudinally how Dutch mothers change their corner vowels, voiceless fricatives, and pitch when speaking to their infant at 11 and 15 months of age. In comparison to adult-directed speech (ADS), Dutch IDS has a smaller vowel space, higher second and third formant frequencies in the vowels, and a higher spectral frequency in the fricatives. The formants of the vowels and spectral frequency of the fricatives are raised more strongly for infants at 11 than at 15 months, while the pitch is more extreme in IDS to 15-month olds. These results show that enhanced positive affect is the main factor influencing Dutch mothers' realisation of speech sounds in IDS, especially to younger infants. This study provides evidence that mothers' expression of emotion in IDS can influence the realisation of speech sounds, and that the loss or gain of speech clarity may be secondary effects of affect. PMID- 24239879 TI - Infants' ability to extract three-dimensional shape from coherent motion. AB - Our capacity to perceive three-dimensional (3D) object structure from two dimensional (2D) retinal input is fundamental to object perception. The present research examined infants' ability to extract 3D form from structure-from-motion (SFM) displays using a familiarization/visual-paired-comparison paradigm. In SFM displays dots are projected onto the surfaces of a shape that rotates around a 3D axis and it is the coherent structure of the dots' motion that gives rise to the percept of shape. Infants mean age 4.5 and 9 months were familiarized to a SFM display (e.g., cylinder); in test they were presented the familiar SFM display paired with a novel SFM display (e.g., cube). Infants in both age groups displayed a significant preference for the novel SFM test display. These results are consistent with those obtained previously using habituation paradigms and provide converging evidence for infants' early emerging capacity to use coherent motion - in the absence of figural information - as a cue to depth structure. In addition, these results demonstrate that infants' ability to extract 3D shape from coherent motion can be successfully assessed with a neuroimaging-friendly protocol, which was one of the goals of this study. PMID- 24239880 TI - Validity and clinical utility of functional assessments in children with cerebral palsy. AB - OBJECTIVE: To examine the validity and clinical utility of functional assessments (1-minute walk test, 10-meter walk test, Timed Up & Go [TUG] test, Timed Up and Down Stairs [TUDS] test, sit-to-stand [STS] test, and lateral step-up [LSU] test). DESIGN: Cross-sectional study. SETTING: Four special schools for adolescents with physical disabilities. PARTICIPANTS: Adolescents with spastic tetraplegia and diplegia (at levels I-III) were selected through convenience sampling (N=35; mean age, 14.97+/-2.03y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: GMFM-88 (dimensions D and E), 1-minute walk, 10-meter walk, TUG, TUDS, STS, and LSU tests. Data were analyzed using Pearson intercorrelations, multiple regression analysis, and multivariate analysis of variance (MANOVA). RESULTS: Significant moderate to high intercorrelations were found. Three significant positive predictors emerged (1-minute walk, 10-meter walk, and LSU) with the following regression equation: YGMFM-88 (dimensions D and E) = 5.708 + .402 * X1-minute walk + .920 * XLSU + .404 * X10-meter walk The MANOVA was significant (Lambda=.163, F=14.732, P<.001, eta(2)=.596), and post hoc comparisons revealed significant differences across Gross Motor Function Classification System Expanded and Revised levels in all paired comparisons for the 1-minute walk and LSU tests. For the 10-meter walk test, significant differences were evident in the level I versus level III and level II versus level III comparisons. No significant differences were found in the 10-meter walk test between levels I and II. CONCLUSIONS: These functional assessments (1-minute walk, LSU, and 10-meter walk tests) are simple to administer, quick, low cost, and user-friendly. Although these assessments are not a substitute for the criterion standard (GMFM-88), they may be used for a quick assessment in adolescents with cerebral palsy (levels I-III) either at school or during rehabilitation, especially when time is limited. PMID- 24239881 TI - Efficacy of coupling repetitive transcranial magnetic stimulation and physical therapy to reduce upper-limb spasticity in patients with stroke: a randomized controlled trial. AB - OBJECTIVE: To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation (rTMS) for decreasing upper-limb muscle tone after chronic stroke. DESIGN: A randomized sham-controlled trial with a 4-week follow-up. SETTING: Research hospital. PARTICIPANTS: Patients with stroke (N=20) with poststroke upper limb spasticity. INTERVENTIONS: The experimental group received rTMS to the primary motor cortex of the unaffected side (1500 pulses; 1Hz; 90% of resting motor threshold for the first dorsal interosseous muscle) in 10 sessions, 3d/wk, and physical therapy (PT). The control group received sham stimulation and PT. MAIN OUTCOME MEASURES: Modified Ashworth scale (MAS), upper-extremity Fugl-Meyer assessment, FIM, range of motion, and stroke-specific quality-of-life scale. All outcomes were measured at baseline, after treatment (postintervention), and at a 4-week follow-up. A clinically important difference was defined as a reduction of >=1 in the MAS score. RESULTS: Friedman test revealed that PT is efficient for significantly reducing the upper limb spasticity of patients only when it is associated with rTMS. In the experimental group, 90% of the patients at postintervention and 55.5% at follow-up showed a decrease of >=1 in the MAS score, representing clinically important differences. In the control group, 30% of the patients at postintervention and 22.2% at follow-up experienced clinically meaningful changes. There were no differences between the groups at any time for any of the other outcome measures, indicating that both groups demonstrated similar behaviors over time for all variables. CONCLUSIONS: rTMS associated with PT can be beneficial in reducing poststroke spasticity. However, more studies are needed to clarify the clinical changes underlying the reduction in spasticity induced by noninvasive brain stimulations. PMID- 24239882 TI - Regulation of adult hematopoiesis by the a disintegrin and metalloproteinase 10 (ADAM10). AB - Adult hematopoiesis requires tightly regulated cell-cell interactions between hematopoietic cells and the bone marrow stromal microenvironment. We addressed the question if the ectodomain sheddase ADAM10 is essential to regulate adult hematopoiesis. Induced ADAM10 deletion in hematopoietic cells resulted in morphological and histological abnormalities that resemble an unclassified myeloproliferative disorder (MPD). The MPD was characterized by an expansion of granulocytic subpopulations and their infiltration of peripheral hematopoietic tissues, the development of hepatosplenomegaly with extramedullary erythropoiesis, lymphnodepathy and death of the mice around 20weeks after induction. ADAM10 expression analysis during the different stages of the MPD revealed that non-targeted hematopoietic cells repopulated the immune system of the ADAM10-deficient mice. Examination of mice with a myeloid- or epidermis specific deletion of ADAM10 and bone marrow transplantation (BMT) experiments indicated that the development of the MPD can be triggered by non-cell autonomous effects. We found that plasma levels of clinical markers for MPD such as G-CSF, TIMP-1 and IL-16 were significantly elevated in ADAM10-deficient mice. Our findings indicate that a tightly controlled ADAM10 expression is needed to balance hematopoietic cell-fate decisions in adult mice. PMID- 24239883 TI - Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells. AB - Though poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have benefits in combination with radiotherapy in prostate cancers, few is known about the exactly role and underlying mechanism of PARP1 in combination with chemotherapy agents. Here our data revealed that inhibition of PARP1 by small interfering RNA (siRNA) could enhance docetaxel's activity against PC3 cells, which is associated with an accelerate repression of EGF/Akt/FOXO1 signaling pathway. Our results provide a novel role of PARP1 in transcription regulation of EGFR/Akt/FOXO1 signaling pathway and indicate that PARP1 siRNA combined with docetaxel can be an innovative treatment strategy to potentially improve outcomes in CRPC patients. PMID- 24239884 TI - Biofilm vs. planktonic bacterial mode of growth: which do human macrophages prefer? AB - Although the natural mode of bacterial growth in nature is as biofilm, almost all antimicrobial and immunological tests are routinely developed using planktonic inoculums. Bacterial biofilms protect the microbial community from external damage and promote the persistence of chronic infections. In this study, interactions between human macrophages and bacterial inoculums of planktonic and biofilm modes of growth have been explored using Escherichia coli (E. coli) K12. Human macrophages phagocytize planktonic E. coli more efficiently than bacteria grown in a biofilm. Moreover, they prefer to phagocytize planktonic bacteria. In this context, CD64 expression is involved. Our data indicate that bacteria with "a biofilm background" avoid phagocytosis by naive macrophages, which could create a favorable environment for chronic infection. Our findings were corroborated in a clinical O25b-ST131 ESBL-producer E. coli isolate, which caused urinary tract infections. PMID- 24239885 TI - Community behavior and amyloid-associated phenotypes among a panel of uropathogenic E. coli. AB - Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infection and engage in a coordinated genetic and molecular cascade to colonize the urinary tract. Disrupting the assembly and/or function of virulence factors and bacterial biofilms has emerged as an attractive target for the development of new therapeutic strategies to prevent and treat urinary tract infection, particularly in the era of increasing antibiotic resistance among human pathogens. UPEC vary widely in their genetic and molecular phenotypes and more data are needed to understand the features that distinguish isolates as more or less virulent and as more robust biofilm formers or poor biofilm formers. Curli are extracellular functional amyloid fibers produced by E. coli that contribute to pathogenesis and influence the host response during urinary tract infection (UTI). We have examined the production of curli and curli-associated phenotypes including biofilm formation among a specific panel of human clinical UPEC that has been studied extensively in the mouse model of UTI. Motility, curli production, and curli-associated biofilm formation attached to plastic were the most prevalent behaviors, shared by most clinical isolates. We discuss these results in the context on the previously reported behavior and phenotypes of these isolates in the murine cystitis model in vivo. PMID- 24239886 TI - Increased susceptibility to Klebsiella pneumonia and mortality in GSNOR-deficient mice. AB - S-nitrosoglutathione reductase (GSNOR) is a key denitrosylase and critically important for protecting immune and other cells from nitrosative stress. Pharmacological inhibition of GSNOR is being actively pursued as a therapeutic approach to increase S-nitrosoglutathione levels for the treatment of asthma and cystic fibrosis. In the present study, we employed GSNOR-deficient (GSNOR(-/-)) mice to investigate whether inactivation of GSNOR may increase susceptibility to pulmonary infection by Klebsiella pneumoniae, a common cause of nosocomial pneumonia. We found that compared to wild-type mice, bacterial colony forming units 48 h after intranasal infection with K. pneumoniae were increased over 4 folds in lung and spleen and strikingly, over a 1000-folds in blood of GSNOR(-/-) mice. Lung injury was comparable between infected wild-type and GSNOR(-/-) mice, but inflammation and injury was significantly elevated in spleen of GSNOR(-/-) mice. Whereas all wild-type mice survived 48 h after infection, 10 of 23 GSNOR(-/ ) mice died. Thus, GSNOR appears to play a crucial role in controlling pulmonary and systemic infection by K. pneumoniae. Our results suggest that patients treated in clinical trials with inhibitors of GSNOR should be carefully monitored for signs of infection. PMID- 24239887 TI - Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense. AB - Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8 fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense. PMID- 24239888 TI - Adipokinetic hormones of the two extant apterygotan insect orders, Archaeognatha and Zygentoma. AB - Two extant apterygotan insect orders, Archaeognatha and Zygentoma, are investigated with respect to the identity of neuropeptides belonging to the adipokinetic hormone (AKH) peptide family; this is the first report on AKH peptide structures in the so-called primitive insects and the first of any peptide in the Archaeognatha. In the lepismatid, Thermobia domestica, and the machilid, Petrobius maritimus, a single AKH peptide is identified and sequenced from each species; neither sequence is novel and has previously been shown in corpora cardiaca (CC) of cockroaches (Peram-CAH-I) and dragonflies (Anaim-AKH), respectively. These octapeptides differ from each other only in one position (Asn(7) in the lepismatid and Ser(7) in the machilid). The biological relevance of these peptides was investigated and we speculate that they are likely involved in the mobilisation of lipids in the apterygotes. Immunocytochemistry with an antibody directed against an AKH revealed a well-developed pair of CC in T. domestica and another lepismatid, the fishmoth Ctenolepisma longicaudata; a cluster of immunopositive cells are located retrocerebrally in tissue sections of P. maritimus which may be the CC. PMID- 24239889 TI - Vasopressin receptors and pharmacological chaperones: from functional rescue to promising therapeutic strategies. AB - Conformational diseases result from protein misfolding and/or aggregation and constitute a major public health problem. Congenital Nephrogenic Diabetes Insipidus is a typical conformational disease. In most of the cases, it is associated to inactivating mutations of the renal arginine-vasopressin V2 receptor gene leading to misfolding and intracellular retention of the receptor, causing the inability of patients to concentrate their urine in response to the antidiuretic hormone. Cell-permeable pharmacological chaperones have been successfully challenged to restore plasma membrane localization of the receptor mutants and to rescue their function. Interestingly, different classes of specific ligands such as antagonists (vaptans), agonists as well as biased agonists of the V2 receptor have proven their usefulness as efficient pharmacochaperones. These compounds represent a potential therapeutic treatment of this X-linked genetic pathology. PMID- 24239890 TI - Ethnomedicinal plants to cure skin diseases-an account of the traditional knowledge in the coastal parts of Central Western Ghats, Karnataka, India. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Documentation of ethnomedicinal knowledge pertaining to the treatment of different types of skin diseases from the Central Western Ghats of India, a rich habitat of different ethnic communities. MATERIALS AND METHODS: Frequent field surveys were carried out to invent the 'key informants' in the treatment of skin diseases in the study area. The information was collected through semi-structured open ended interviews with questionnaire in their local Kannada language. All medicinal plants recorded for the treatment of skin diseases were photographed in the field; voucher specimens were made subsequently and are deposited in the Herbarium, P.G. Department of Botany, Karnatak University, Dharwad. The information such as botanical name, status, family, vernacular name, habit and habitat, analysis like percentage of parts used, percentage of drug preparations, use value (UV), informants consensus factor (ICF), fidelity level (FL) and correlation between UV and use mention (Np) of the plants are provided. RESULTS: In all, 48 informants were interviewed. Amongst which 38 were the 'key informants' who gave the information exclusively about the treatment of skin diseases. Among 102 plant species collected, seven species are endemic to India and eleven species have their nativity outside India. Twelve species could be considered as new claims for skin diseases as their use has not been mentioned in Ayurveda or any other research articles surveyed. Of all the drug formulations, paste is the most preferred method (50%) followed by oil extraction (18.89%), juice (14.44%), ash (4.44%) etc. The highest UV is for Pongamia pinnata, Naregamia alata, Randia dumetorum and Girardinia diversifolia (1.50 each). The treatment for different types of skin diseases by the herbal healers are classified into 13 categories, out of which ringworm scored the highest ICF value. Similarly, the 100% FL value scored was in the order of 10 plants for boils, 4 plants for different types of sore, 2 plants for ringworm, intertrigo, eczema and pruritus respectively. As Caesalpinia mimosoides and Basella alba in the treatment of boils, Hygrophila schulli for inter trigo, Cissus discolor for ringworm, Mammea suriga for eczema scored high FL and high Np value, they can be considered as important species. CONCLUSIONS: The documentation and data analysis of the ethnomedicinal knowledge in the coastal regions of Uttara Kannada district of Central Western Ghats have provided the information about important plants in the treatment of different types of skin diseases. Further scientific analysis of such plants may provide novel compounds for the treatment of skin diseases. PMID- 24239891 TI - Evaluation of subchronic inhalation toxicity of methylcyclopentane in rats. AB - The aim of this study was to verify subchronic inhalation toxicity of methylcyclopentane (CAS No. 96-37-7) in Sprague-Dawley rats. Four groups of 10 rats of each gender were exposed to methylcyclopentane vapor by whole-body inhalation at concentrations of 0, 290, 1300, or 5870 ppm for 6h per day, 5 days/week over a 13-week period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. Exposure-related clinical signs (salivation and rubbing) were observed in both genders of the 5870 ppm group. There was an increase in liver weight for both genders but the kidney weight was only higher in females than controls. However, no toxicologically significant changes were observed in body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings, or histopathology in any of the treatment groups. Under the present experimental conditions, the target organs were determined to be kidney and liver in rats. The no-observed-adverse-effect concentration was considered to be 1300 ppm/6h/day in rats. PMID- 24239892 TI - Pilot toxicokinetic study and absolute oral bioavailability of the Fusarium mycotoxin enniatin B1 in pigs. AB - The aim of present study was to reveal the toxicokinetic properties and absolute oral bioavailability of enniatin B1 in pigs. Five pigs were administered this Fusarium mycotoxin per os and intravenously in a two-way cross-over design. The toxicokinetic profile fitted a two-compartmental model. Enniatin B1 is rapidly absorbed after oral administration (T(1/2a)=0.15 h, Tmax=0.24h) and rapidly distributed and eliminated as well (T(1/2elalpha)=0.15 h; T(1/2elbeta)=1.57 h). The absolute oral bioavailability is high (90.9%), indicating a clear systemic exposure. After intravenous administration, the mycotoxin is distributed and eliminated rapidly (T(1/2elalpha)=0.15 h; T(1/2elbeta)=1.13 h), in accordance with oral administration. PMID- 24239893 TI - Resveratrol contributes to chemosensitivity of malignant mesothelioma cells with activation of p53. AB - Resveratrol is a naturally occurring polyphenolic phytoalexin with chemopreventive properties. We previously reported a synergistic anti proliferative effect of resveratrol and clofarabine against malignant mesothelioma (MM) cells. Here, we further investigated molecular mechanisms involved in the synergistic interaction of these compounds in MM MSTO-211H cells. Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO 211H cells, but not in normal mesothelial MeT-5A cells. Combination treatment up regulated the levels of p-p53, cleaved caspase-3, and cleaved PARP proteins. Gene silencing with p53-targeting siRNA attenuated the sensitivity of cells to the combined treatment of two compounds. Analyses of p53 DNA binding assay, p53 reporter gene assay, and RTP-CR toward p53-regulated genes, including Bax, PUMA, Noxa and p21, demonstrated that induced p-p53 is transcriptionally active. These results were further confirmed by the siRNA-mediated knockdown of p53 gene. Combination treatment significantly caused the accumulation of cells at G1 phase with the increases in the sub-G0/G1 peak, DNA ladder, nuclear fragmentation, and caspase-3/7 activity. Taken together, these results demonstrate that resveratrol and clofarabine synergistically elicit apoptotic signal via a p53-dependent pathway, and provide a scientific rationale for clinical evaluation of resveratrol as a promising chemopotentiator in MM. PMID- 24239894 TI - Proteomic analysis identifies differentially expressed proteins after red propolis treatment in Hep-2 cells. AB - Here we investigated alterations in the protein profile of Hep-2 treated with red propolis using two-dimensional electrophoresis associated to mass spectrometry and apoptotic rates of cells treated with and without red propolis extracts through TUNEL and Annexin-V assays. A total of 325 spots were manually excised from the two-dimensional gel electrophoresis and 177 proteins were identified using LC-MS-MS. Among all proteins identified that presented differential expression, most were down-regulated in presence of red propolis extract at a concentration of 120 MUg/mL (IC50): GRP78, PRDX2, LDHB, VIM and TUBA1A. Only two up-regulated proteins were identified in this study in the non-cytotoxic (6 MUg/mL) red propolis treated group: RPLP0 and RAD23B. TUNEL staining assay showed a markedly increase in the mid- to late-stage apoptosis of Hep-2 cells induced by red propolis at concentrations of 60 and 120 MUg/mL when compared with non treated cells. The increase of late apoptosis was confirmed by in situ Annexin-V analysis in which red propolis extract induced late apoptosis in a dose-dependent manner. The differences in tumor cell protein profiles warrant further investigations including isolation of major bioactive compounds of red propolis in different cell lines using proteomics and molecular tests to validate the protein expression here observed. PMID- 24239895 TI - Drug memory substitution during re-consolidation: a single inhibitory autoreceptor apomorphine treatment given during psychostimulant memory re consolidation replaces psychostimulant conditioning with conditioned inhibition and reverses psychostimulant sensitization. AB - Psychostimulant conditioning and sensitization effects have proven to be difficult to eliminate using behavioral methods. We used a low autoreceptor dose of apomorphine in counter-conditioning and memory re-consolidation protocols to modify conditioned and sensitized responses induced by a high dose of apomorphine. Rats received five daily treatments of apomorphine (2.0mg/kg) and were tested in an arena for 30 min to induce conditioning and sensitization. Conditioning was validated in a brief 5 min non-drug conditioning test and sensitization by a 2.0 apomorphine challenge test. Next, the counter-conditioning and memory re-consolidation protocols were initiated. In counter-conditioning, vehicle or 0.05 mg/kg apomorphine was given either 15 min or immediately before a 5 min arena test. In the memory re-consolidation protocol, the vehicle and 0.05 apomorphine treatments were administered post-trial either immediately after or 15 min after the 5 min arena test. Effects were assessed with a 5 min saline conditioning test and a second 2.0mg/kg apomorphine challenge test. The counter conditioning protocol induced hypolocomotion and but did not induce a conditioned hypo-locomotion and did not alter the sensitized response. The 15 min post-trial treatment did not affect either the conditioned or the sensitized responses. The immediate post-trial treatment eliminated sensitization and induced a conditioned hypoactivity response. These results highlight the memory re-consolidation period as a critical target for drug memory substitution and suggest the potential utility of the pharmacological inhibition of dopamine activity given as a therapeutic drug memory replacement during addictive drug memory re consolidation. PMID- 24239897 TI - Epigenetic regulation of the tissue-specific expression of human UDP glucuronosyltransferase (UGT) 1A10. AB - Human UDP-glucuronosyltransferase (UGT) 1A10 is not expressed in the liver; however, UGT1A10 is highly expressed in the intestine, contributing to presystemic first-pass metabolism. Earlier studies revealed that hepatocyte nuclear factor (HNF) 1alpha and Sp1, as well as an intestine-specific transcription factor, caudal type homeobox (Cdx) 2, are involved in the constitutive expression of UGT1A10. However, why UGT1A10 is not expressed in the liver, where HNF1alpha and Sp1 are abundantly expressed, is unknown. In this study, we sought to elucidate the mechanism, focusing on epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region (-264 to +117) around the UGT1A10 promoter was hypermethylated (89%) in hepatocytes, whereas the UGT1A10 promoter was hypomethylated (11%) in the epithelium of the small intestine. A luciferase assay revealed that the methylation of the UGT1A10 promoter by SssI methylase abrogated transactivity even with overexpressed Cdx2 and HNF1alpha. The UGT1A10 promoter was highly methylated (86%) in liver-derived HuH-7 cells, where UGT1A10 is not expressed. In contrast, the UGT1A10 promoter was hardly methylated (19%) in colon-derived LS180 cells, where UGT1A10 is expressed. Treatment with 5-aza-2'-deoxycitidine (5-Aza-dC), an inhibitor of DNA methylation, resulted in an increase in UGT1A10 expression only in HuH-7 cells. Moreover, overexpression of HNF1alpha and Cdx2 further increased UGT1A10 expression only in the presence of 5-Aza-dC. Collectively, we found that DNA hypermethylation would interfere with the binding of HNF1alpha and Cdx2, resulting in the defective expression of UGT1A10 in human liver. Thus, epigenetic regulation is one of the mechanisms that determine the tissue-specific expression of UGT1A10. PMID- 24239896 TI - Heme oxygenase-1 counteracts contrast media-induced endothelial cell dysfunction. AB - Endothelial cell (EC) dysfunction is involved in the pathogenesis of contrast induced acute kidney injury, which is a major adverse event following coronary angiography. In this study, we evaluated the effect of contrast media (CM) on human EC proliferation, migration, and inflammation, and determined if heme oxygenase-1 (HO-1) influences the biological actions of CM. We found that three distinct CM, including high-osmolar (diatrizoate), low-osmolar (iopamidol), and iso-osmolar (iodixanol), stimulated the expression of HO-1 protein and mRNA. The induction of HO-1 was associated with an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS). CM also stimulated HO-1 promoter activity and this was prevented by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. In addition, the CM-mediated induction of HO-1 and activation of Nrf2 was abolished by acetylcysteine. Finally, CM inhibited the proliferation and migration of ECs and stimulated the expression of intercellular adhesion molecule-1 and the adhesion of monocytes on ECs. Inhibition or silencing of HO-1 exacerbated the anti-proliferative and inflammatory actions of CM but had no effect on the anti-migratory effect. Thus, induction of HO-1 via the ROS-Nrf2 pathway counteracts the anti-proliferative and inflammatory actions of CM. Therapeutic approaches targeting HO-1 may provide a novel approach in preventing CM-induced endothelial and organ dysfunction. PMID- 24239898 TI - P-glycoprotein associates with Anxa2 and promotes invasion in multidrug resistant breast cancer cells. AB - Several recent studies have suggested that the acquisition of the multidrug resistance (MDR) phenotype is associated with elevated invasion and metastasis of tumor cells. P-glycoprotein (P-gp), the major determinant in the generation of the MDR phenotype, was reported to be correlated with a more aggressive phenotype and poor prognosis in many forms of malignancies. However, a clear understanding of the association is still lacking. We previously showed that Anxa2, a calcium dependent phospholipid-binding protein, interacts with P-gp and contributes to the invasiveness of MDR breast cancer cells. In the present study, a strong positive correlation between MDR1 and Anxa2 mRNA expression in invasive breast cancer tissues during cancer progression was observed. In addition, exposure to adriamycin significantly enhanced motility in breast cancer cells and increased levels of P-gp and Anxa2. Moreover, inhibition of P-gp activity, using selective P-gp modulators, was found to significantly inhibit the invasive capacity of MCF 7/ADR cells without affecting the interaction and co-localization between P-gp and Anxa2. However, suppression of P-gp pump activity and knockdown of MDR1 expression both disrupted adriamycin-induced Anxa2 phosphorylation. Interestingly, P-gp was further demonstrated to interact with Src, a tyrosine kinase upstream of Anxa2. Taken together, our results indicate that P-gp may promote the invasion of MDR breast cancer cells by modulating the tyrosine phosphorylation of Anxa2. The interaction between Anxa2 and P-gp is possibly, at least in part, responsible for the association between MDR and invasive potential in breast cancer cells. PMID- 24239899 TI - A polymeric device for controlled transscleral multi-drug delivery to the posterior segment of the eye. AB - The design of drug delivery systems that can deliver multiple drugs to the posterior segment of the eye is a challenging task in retinal disease treatments. We report a polymeric device for multi-drug transscleral delivery at independently controlled release rates. The device comprises a microfabricated reservoir, controlled-release cover and three different fluorescent formulations, which were made of photopolymeized tri(ethyleneglycol)dimethacrylate (TEGDM) and poly(ethyleneglycol)dimethacrylate (PEGDM). The release rate of each fluorescent is controlled by varying the PEGDM/TEGDM ratio in its formulation and the cover. The release kinetics appeared to be related to the swelling ratio of the PEGDM/TEGDM polymers. When the devices were implanted onto rat sclerae, fluorescence was observable in the ocular tissues during 4 weeks' implantation and distributed locally around the implantation site. Our polymeric system, which can administer multiple compounds with distinct kinetics, provides prolonged action and less invasive transscleral administration, and is expected to provide new tools for the treatment of posterior eye diseases with new therapeutic modalities. PMID- 24239900 TI - Study and evaluation of mechanisms of dual targeting drug delivery system with tumor microenvironment assays compared with normal assays. AB - A dual targeting delivery system was developed to completely conquer the two barriers that glioma treatment faces: the blood-brain barrier (BBB) and the brain glioma barrier. Recently, a system comprising AS1411 aptamer (for glioma targeting) and TGN peptide (for BBB targeting) modified nanoparticles (AsTNPs) was developed, which can effectively target brain glioma and improve the survival of glioma-bearing mice. However, the in vitro models currently used are far too different from the in vivo tumor microenvironment that the glioma targeting delivery system actually faces. In this study, the pharmacology mechanisms of AsTNPs were explored in several models that imitated the tumor microenvironment. AsTNPs can be selectively taken up by endothelial and glioma cells, effectively penetrating the BBB and brain-glioma barriers to reach glioma cells and display their anti-glioma effect. The cell monolayers, tumor spheroids and coculture systems were more suitable in vitro models for the pharmacology evaluation of targeted drug delivery systems. PMID- 24239901 TI - Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. AB - In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix(r)CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-angle X-ray scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112-220 nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and polyethylene glycol (PEG)-PEVs (~ 68%). Histology showed that PEG-PEVs provided an extensive re-epithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage. PMID- 24239902 TI - The influence of short-term memory on standard discrimination and cued identification olfactory tasks. AB - BACKGROUND: Amongst the techniques to assess olfactory functions, discrimination and cued identification are those most prone to the influence of odour short-term memory (STM). Discrimination task requires participants to detect the odd one out of three presented odourants. As re-smelling is not permitted, an un-intended STM load may generate, even though the task purports to assess discrimination ability. Analogously, cued identification task requires participants to smell an odour, and then select a label from three or four alternatives. As the interval between smelling and reading each label increases this too imposes a STM load, even though the task aims to measure identification ability. NEW METHOD: We tested whether modifying task design to reduce STM load improve performance on these tests. We examined five age-groups of participants (Adolescents, Young adults, Middle-aged, Elderly, very Elderly), some of whom should be more prone to the effects of STM load than others, on standard and modified tests of discrimination and identification. RESULTS: We found that using a technique to reduce STM load improved performance, especially for the very Elderly and Adolescent groups. COMPARISON WITH EXISTING METHODS: Sources of error are now prevented. CONCLUSIONS: Findings indicate that STM load can adversely affect performance in groups vulnerable from memory impairment (i.e., very Elderly) and in those who may still be acquiring memory-based representations of familiar odours (i.e., Adolescents). It may be that adults in general would be even more sensitive to the effects of olfactory STM load reduction, if the odour-related task was more difficult. PMID- 24239903 TI - Automated interhemispheric surface extraction in T1-weighted MRI using intensity and symmetry information. AB - BACKGROUND: Localizing the human interhemispheric region is of interest in image analysis mainly because it can be used for hemisphere separation and as a preprocessing step for interhemispheric structure localization. Many existing methods focus on only one of these applications. NEW METHOD: Here a new Intensity and Symmetry based Interhemispheric Surface extraction method (ISIS) that enables both applications is presented. A combination of voxel intensity and local symmetry is used to optimize a surface from T1-weighted MRI. RESULTS: ISIS was evaluated in regard to cerebral hemisphere separation using manual segmentations. It was also evaluated in regard to being a preprocessing step for interhemispheric structure localization using manually placed landmarks. COMPARISON WITH EXISTING METHODS: Results were compared to cerebral hemisphere separations by BrainVisa and Freesurfer as well as to a midsagittal plane (MSP) extraction method. ISIS had less misclassified voxels than BrainVisa (ISIS: 0.119+/-0.114%, BrainVisa: 0.138+/-0.084%, p=0.020). Freesurfer had less misclassified voxels than ISIS for one dataset (ISIS: 0.063+/-0.056%, Freesurfer: 0.049+/-0.044%, p=0.019), but failed to produce usable results for another. Total voxel distance from all manual landmarks did not differ significantly between ISIS and the MSP method (ISIS: 4.00+/-1.88, MSP: 4.47+/-4.97). CONCLUSIONS: ISIS was found successful in both cerebral hemisphere separation and as a preprocessing step for interhemispheric structure localization. It needs no time consuming preprocessing and extracts the interhemispheric surface in less than 30 s. PMID- 24239904 TI - Mass spectrometric studies on the in vivo metabolism and excretion of SIRT1 activating drugs in rat urine, dried blood spots, and plasma samples for doping control purposes. AB - The NAD(+) depending enzyme SIRT1 regulates the mitochondrial biogenesis, fat and glucose metabolism through catalyzing the deacetylation of several metabolism related protein-substrates. Recently, synthetic activators of SIRT1 referred to as STACs (Sirtuin activating compounds, e.g. SRT2104) were identified and tested in clinical studies for the treatment of aging-related diseases such as type 2 diabetes, Alzheimer's and obesity. Although the mechanism of SIRT1 activation by small molecules has caused considerable controversy, STACs demonstrated a significant performance enhancement in mice experiments including an improvement of endurance, muscle strength, and locomotor behavior. Due to their potential to increase exercise tolerance in healthy individuals, SIRT1 activators are currently being monitored by anti-doping authorities. In the present study, the in vivo metabolic clearance of three SIRT1 activators was investigated in rats by the collection of urine, DBS (dried blood spots) and plasma samples following a single oral administration. The resulting metabolic products were studied by positive electrospray ionization - (tandem) mass spectrometry and confirmed by the comparison with in vitro generated metabolites using human and rat liver microsomal preparations. Subsequently, a screening procedure for five SIRT1 activators and the metabolite M1-SRT1720 in DBS specimens was developed. Liquid liquid-extraction and liquid chromatography/tandem mass spectrometry was employed based on diagnostic ion transitions recorded in multiple reaction monitoring mode and two deuterated internal standards namely d8-SRT1720 and d8-M1-SRT1720 were utilized. The doping control assay was characterized with regard to specificity, limit of detection (10-50ng/ml), recovery (65-83%) and imprecision (7-20%) and ion suppression/enhancement effects (<10%), demonstrating its fitness-for-purpose for sports drug testing applications. PMID- 24239905 TI - Systematic development of an UPLC-MS/MS method for the determination of tricyclic antidepressants in human urine. AB - Tricyclic antidepressants have been prescribed for the treatment of depression and other disorders since their discovery in the 1950s but have been replaced in recent decades by newer drugs with more favorable side effect profiles. However, for some patients and conditions, tricyclic antidepressants remain the drug of choice. A fast, sensitive, and robust UPLC-MS/MS method for the monitoring of amitriptyline, nortriptyline, imipramine, doxepin, and desipramine in human urine has been developed using a pre-defined and systematic method development approach. The method was developed using sub-2-MUm particle technology, providing a state-of-the-art alternative to older methods. Total cycle time was 2.5min. Human urine samples (200MUL) were prepared using an Oasis((r)) WCX MUElution solid-phase extraction plate, which provided good recovery for all analytes (>92%) and low matrix effects (absolute matrix effects <10%). Standard curves were linear over the range 0.02-250ng/mL with r(2) values>0.994. The method was evaluated against current FDA guidelines and was applied to the analysis of patient samples, including an assessment of incurred sample reanalysis (ISR). PMID- 24239906 TI - Immobilization of the enzyme GpdQ on magnetite nanoparticles for organophosphate pesticide bioremediation. AB - Annually thousands of people die or suffer from organophosphate (pesticide) poisoning. In order to remove these toxic compounds from the environment, the use of enzymes as bioremediators has been proposed. We report here a Ser127Ala mutant based on the enzyme glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes. The mutant, with improved metal binding abilities, has been immobilized using glutaraldehyde on PAMAM dendrimer-modified magnetite nanoparticles. The immobilized system was characterized using elemental analysis as well as infrared, transmission electron and X-ray photoelectron spectroscopies. The amount of GpdQ that was immobilized with the optimized procedure was 1.488 nmol per g MNP. A kinetic assay has been designed to evaluate the activity of the system towards organophosphoester substrates. The specific activity towards BPNPP directly after immobilization was 3.55 MUmol mg(-1)min(-1), after one week 3.39 MUmol mg(-1)min(-1) and after 120 days 3.36 MUmol mg(-1)min(-1), demonstrating that the immobilized enzyme was active for multiple cycles and could be stored on the nanoparticles for a prolonged period. PMID- 24239907 TI - Enhanced cytotoxic activity of bile acid cisplatin derivatives by conjugation with gold nanoparticles. AB - This article explores the potential cytotoxic activity of bile-acid cisplatin derivatives like bisursodeoxycholate(ethylenediamine)platinum(II), PtU2, when conjugated with gold nanoparticles, being a promising alternative to cisplatin in the treatment of cancer due to their lower toxicity. For our purpose we analyzed the intracellular delivery ability of these compounds after conjugation with 20 nm gold nanoparticles (PtU2-AuNPs) in the MG63 (osteosarcoma) cell line. Same platinum uptake after incubation with PtU2 and PtU2-AuNPs-derivatives is associated with a higher cytotoxic activity in case of the platinum-gold nanoparticle conjugate, the overall IC50 of PtU2 being reduced more than 10 fold for these new conjugates. When conjugated with gold nanoparticles, this bile-acid derivative is more efficient than the platinum compound alone in terms of their cytotoxic activity. PMID- 24239908 TI - Formation of oxo-centered trinuclear chromium carboxylate complexes and hydrolysis of Cr3 as established by paramagnetic (2)H NMR spectroscopy. AB - Paramagnetic (2)H NMR techniques have been utilized to study the mechanism of formation of the oxo-bridged trinuclear Cr(III) carboxylate assembly [Cr3O(O2CCD3)6(H2O)3](+) from [Cr(H2O)6](3+) and d4-acetic acid. These studies reveal a complex mechanism dominated by the involvement of dinuclear intermediates. The oxo-bridged trinuclear Cr(III) carboxylate assembly [Cr3O(O2CCH2CH3)6(H2O)3](+) has been suggested for use as a chromium nutritional supplement and therapeutic agent as it is readily absorbed and has been proposed to enter cells intact. The paramagnetic (2)H NMR technique has been utilized to follow the stability of this Cr(III) carboxylate assembly in biologically relevant media; its stability is consistent with the assembly being able to enter cells intact. PMID- 24239909 TI - Synthesis, characterization and antibacterial studies of a copper(II) lomefloxacin ternary complex. AB - Solution behavior of lomefloxacin (lmx) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):lmx:phen ternary complexes are stable. Hence, a novel copper(II) ternary complex of lomefloxacin with the nitrogen donor heterocyclic ligand phen was synthesized and characterized by means of UV-visible and IR spectroscopy, elemental analysis and X-ray crystallography. In the synthesized complex (1), [Cu(lmx)(phen)(NO3)].5H2O, lmx acts as a bidentate ligand coordinating the metal cation, in its anionic form, through the carbonyl and carboxyl oxygens and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth ligand of the penta-coordinated Cu(II) center is occupied axially by an oxygen atom from the nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complex and comparison with free lomefloxacin in various E. coli strains indicated that the Cu-complex is an antimicrobial which is as efficient as the free antibiotic but strongly suggest that the cell intake route of both species is different. Moreover, spectrophotometric stability studies suggest that the solution of the complex synthesized is considerably more photostable than the free fluoroquinolone supporting, therefore, the complex's suitability as a candidate for further biological testing in fluoroquinolone resistant microorganisms with possible reduced side-effects. PMID- 24239910 TI - Deciphering the zinc coordination properties of the prokaryotic zinc finger domain: The solution structure characterization of Ros87 H42A functional mutant. AB - The zinc coordination sphere in prokaryotic zinc finger domain is extremely versatile and influences the stability and the folding property of the domain. Of a particular interest is the fourth zinc coordinating position, which is frequently occupied by two successive histidines, both able to coordinate the metal ion. To clarify their structural and functional role we report the NMR solution structure and the dynamics behavior of Ros87 H42A, which is a functional mutant of Ros87, the DNA binding domain of the Ros protein containing a prokaryotic Cys2His2 zinc finger domain. The structural analysis indicates that reducing the spacer among the two coordinating histidines from 4 (among His37 and His42) amino acids to 3 (among His37 and His41) increases the helicity of the first alpha-helix. At the same time, the second helix appears more mobile in the MUs-ms timescale and the hydrophobic core is reduced. These data explain the high frequency of three-residue His spacers in the eukaryotic zinc finger domain and their absence in the prokaryotic counterpart. Furthermore, the structural comparison shows that the second coordination position is more sensitive to H42A mutation with respect to the first and the third position, providing the rationale of the high variability of the second and the fourth zinc coordinating position in Ros homologs, which adopt different metal coordination but preserve similar tertiary structures and DNA binding activities. Finally, H/D exchange measurements and NMR thermal unfolding analysis indicate that this mutant likely unfolds via a different mechanism with respect to the wild-type. PMID- 24239911 TI - Low-dimensional compounds containing bioactive ligands. V: Synthesis and characterization of novel anticancer Pd(II) ionic compounds with quinolin-8-ol halogen derivatives. AB - Three novel palladium(II) complexes, NH2(CH3)2[PdCl2(CQ)] (1) (CQ=5-chloro-7-iodo quinolin-8-ol), NH2(CH3)2[PdCl2(dClQ)] (2) (dClQ=5,7-dichloro-quinolin-8-ol) and NH2(CH3)2[PdCl2(dBrQ)] (3) (dBrQ=5,7-dibromo-quinolin-8-ol) have been prepared and characterized. Their structures contain square-planar [PdCl2(XQ)](-) complex anions in which deprotonated XQ ligands are coordinated to the Pd atoms via the pyridine nitrogen and the phenolato oxygen atoms, other two cis-positions are occupied by two chlorido ligands. Negative charges of these anions are balanced by uncoordinated dimethylammonium cations. Coordination of the XQ ligands to Pd(II) atom was confirmed by the differences in the stretching nu(OH) and nu(CN) vibrations in the IR spectra of ligands and prepared complexes while bands of aliphatic CH and NH stretching vibrations observed in the spectra of 1-3 confirm the presence of dimethylammonium cations in the complexes. The binding of complexes 1-3 to calf thymus DNA was investigated using UV-visible and fluorescence emission spectrophotometry. The fluorescence spectral results indicate that the complexes can bind to DNA through an intercalative mode. The Stern-Volmer quenching constants obtained from the linear quenching plot are in the 1.04 * 10(4) to 4.35 * 10(4) M(-1) range. The complexes exhibit significant anticancer activity tested on A2780 cells and cisplatin resistant cell line A2780/CP. PMID- 24239912 TI - Multi-targeted organometallic ruthenium(II)-arene anticancer complexes bearing inhibitors of poly(ADP-ribose) polymerase-1: A strategy to improve cytotoxicity. AB - Small-molecule inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have currently drawn much attention as promising chemotherapeutic drug candidates, and there is a need to develop more potent PARP inhibitors with improved bioavailability. Here we report a strategy to improve the cytotoxicity of PARP inhibitors by conjugation with organometallic ruthenium(II)-arene compounds. We also report a systematic study to reveal the mechanism of action of these ruthenium-PARP inhibitor conjugates. The complexes have been synthesized and characterized spectroscopically. The improved antiproliferative activity from the as-prepared complexes in four human cancer cell lines has indicated their potential for further development as antitumor drugs. Cellular uptake study reveals that the most active complex 3 easily entered into cells. Target validation assays show that the complexes inhibited PARP-1 slightly better than the original PARP inhibitors, that complex 3 strongly bound to DNA and inhibited transcription, and that this complex arrested the cell cycle at the G0/G1 stage. This type of information could shed light on the design of the next generation of more active ruthenium-PARP inhibitor conjugates. PMID- 24239913 TI - Complex rhamnolipid mixture characterization and its influence on DPPC bilayer organization. AB - Rhamnolipids (RL) are one of the most important classes of biosurfactants produced by microorganisms using a wide range of carbon sources, from a simple carbon source like glucose to complex wastes such as the used cooking oils used in this work. The objective of this work was to learn about the rhamnolipid phospholipid dipalmitoyl phosphatidyl choline (DPPC) molecular interactions through the behaviour observed in the neat products and four RL/DPPC mixtures. Size and z-potential were used to characterize the size and the charge of the vesicles, and small angle X-ray scattering (SAXS) was used to measure the vesicle bilayer characteristics, and the release of carboxyfluorescein to study the bilayer disrupting effect promoted by rhamnolipids. The results show that rhamnolipids are disposed in ordered bilayers with long repeating distances, which are stabilized by the charging of the bilayer and also by a strong fluidity of the bilayers. The ability of rhamnolipids to increase the fluidity of DPPC bilayers may be related with the strong haemolytic power of these molecules. PMID- 24239914 TI - Decabrominated diphenyl ether (BDE-209) and/or BDE-47 exposure alters protein expression in purified neural stem/progenitor cells determined by proteomics analysis. AB - Polybrominateddiphenyl ethers (PBDEs) are widely utilized as the additive brominated flame retardants in electronic devices, furniture, plastics, rubber foam, and textiles, which exhibit many negative biological effects, especially potential toxic effects on neurodevelopment. In the present study, we applied a proteomics approach to study the effects of decabromodiphenyl ether (BDE-209) and/or tetrabromodiphenyl ether (BDE-47) on the expression of proteins extracted from neural stem/progenitor cells and further explored mechanisms on neurodevelopmental toxicity. We sub-cultured 3-4 generations of neural stem/progenitor cells which were exposed to BDE-209 and/or BDE-47. After a 72-h exposure, we applied two-dimensional gel (2-DE) to identify differentially expressed proteins and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) to determine the protein identity of 25 spots. Western blot analysis was applied to determine the expression of cofilin-1 and vimentin. A total of 39 differential expression protein spots were identified by 2-DE after BDE-209 and/or BDE-47 exposure in the neural stem/progenitor cells, and 19 differentially expressed proteins were identified by MALDI-TOF-MS. Western blot analysis revealed that cofilin-1 and vimentin were differentially expressed in all groups. Expression of both proteins was decreased when the neural stem/progenitor cells were exposed to BDE-209 and were absent when exposed to both BDE-47 and BDE-209. BDE-209 and/or BDE-47 might alter the expression of some proteins of neural stem/progenitor cells. Nineteen proteins were identified by MALDI-TOF-MS, which will provide a useful basis for further study of the mechanisms underlying PBDE-mediated neurotoxicity. PMID- 24239915 TI - Re: detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study: I. Y. Kim, P. K. Modi, E. Sadimin, Y.-S. Ha, J. H. Kim, D. Skarecky, D. Y. Cha, C. O. Wambi, Y.-C. Ou, B. Yuh, S. Park, E. Llukani, D. M. Albala, T. Wilson, T. Ahlering, K. Badani, H. Ahn, D. I. Lee, M. May, W.-J. Kim and d. H. Lee J Urol 2013;190:527-534. PMID- 24239916 TI - Reply by authors. PMID- 24239917 TI - Editorial comment. PMID- 24239918 TI - Re: detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study: I. Y. Kim, P. K. Modi, E. Sadimin, Y.-S. Ha, J. H. Kim, D. Skarecky, D. Y. Cha, C. O. Wambi, Y.-C. Ou, B. Yuh, S. Park, E. Llukani, D. M. Albala, T. Wilson, T. Ahlering, K. Badani, H. Ahn, D. I. Lee, M. May, W.-J. Kim and d. H. Lee J Urol 2013;190:527-534. PMID- 24239919 TI - Cloning and immune characterization of the c-type lysozyme gene in red-spotted grouper, Epinephelus akaara. AB - Lysozyme is an important component of the innate immune response against pathogen infection. The gene coding for c-type lysozyme in red-spotted grouper Epinephelus akaara was cloned and designated EaClys. The complete cDNA contains a 432 bp open reading frame encoding a protein of 144 amino acids displaying 65-91% similarity with the amino acid sequences of human, mouse, chicken, and fish counterparts. Recombinant EaClys (rEaClys) was expressed in Escherichia coli, displayed antibacterial activity against Gram-positive and Gram-negative bacteria, and possessed bactericidal activity against Vibrio alginolyticus. EaClys mRNA was constitutively expressed in all tested E. akaara tissues, and its expression increased after pathogen challenge. Most notably, challenges with LPS, SGIV or V. alginolyticus upregulated EaClys mRNA expression in the head, kidney, and blood. Its expression peaked between 16 and 24 h after challenge before dropping back to the baseline level. By using recombinant cytokines as signaling pathway mimetics and blocking antibodies and chemical inhibitors as pathway inhibitors, we show that LPS-induced lysozyme release from macrophages is promoted by cytokines TNF alpha and IL-1beta, and dependent on NF-kappaB pathway activation. These data suggest that EaClys is a constitutive and inducible acute-phase protein that is involved in the innate immune defense of E. akaara, and provide new clues about the molecular mechanisms that regulate innate immune responses in fish. PMID- 24239920 TI - 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. PMID- 24239921 TI - 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24239922 TI - 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24239923 TI - 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. PMID- 24239924 TI - Concentrations of and application protocols for hydrogen peroxide bleaching gels: effects on pulp cell viability and whitening efficacy. AB - OBJECTIVES: To assess the whitening effectiveness and the trans-enamel/trans dentinal toxicity of experimental tooth-bleaching protocols on pulp cells. METHODS: Enamel/dentine discs individually adapted to trans-well devices were placed on cultured odontoblast-like cells (MDPC-23) or human dental pulp cells (HDPCs). The following groups were formed: G1 - no treatment (control); G2 to G4 35% H2O2, 3 * 15, 1 * 15, and 1 * 5 min, respectively; and G5 to G7 - 17.5% H2O2, 3 * 15, 1 * 15, and 1 * 5 min, respectively. Cell viability and morphology were evaluated immediately after bleaching (T1) and 72 h thereafter (T2). Oxidative stress and cell membrane damage were also assessed (T1). The amount of H2O2 in culture medium was quantified (Mann-Whitney; alpha=5%) and colour change (DeltaE) of enamel was analysed after 3 sessions (Tukey's test; alpha=5%). RESULTS: Cell viability reduction, H2O2 diffusion, cell morphology alteration, oxidative stress, and cell membrane damage occurred in a concentration-/time dependent fashion. The cell viability reduction was significant in all groups for HDPCs and only for G2, G3, and G5 in MDPC-23 cells compared with G1. Significant cell viability and morphology recovery were observed in all groups at T2, except for G2 in HDPCs. The highest DeltaE value was found in G2. However, all groups presented significant DeltaE increases compared with G1. CONCLUSION: Shortening the contact time of a 35%-H2O2 gel for 5 min, or reducing its concentration to 17.5% and applying it for 45, 15, or 5 min produce gradual tooth colour change associated with reduced trans-enamel and trans-dentinal cytotoxicity to pulp cells. CLINICAL SIGNIFICANCE: The experimental protocols tested in the present study provided significant tooth-bleaching improvement associated with decreased toxicity to pulp cells, which may be an interesting alternative to be tested in clinical situations intended to reduce tooth sensitivity and pulp damage. PMID- 24239925 TI - Comparacion mediante Fluorescencia Cuantitativa Inducida por Luz de la Eficacia de un Dentifrico con Arginina al 1.5% y 1450ppm de Fluoruro con un Dentifrico que Contiene 1450ppm de Fluoruro Solamente en el Manejo de Lesiones de Caries en Estadio Temprano. PMID- 24239926 TI - Effect of layered double hydroxide intercalated with fluoride ions on the physical, biological and release properties of a dental composite resin. AB - OBJECTIVES: The aim of this work was the preparation of a new fluoride-releasing dental material characterized by a release of fluoride relatively constant over time without any initial toxic burst effect. This type of delivery is obtained by a matrix controlled elution and elicits the beneficial effect of a low amount of fluoride on human dental pulp stem cells (hDPSCs) towards mature phenotype. METHODS: The modified hydrotalcite intercalated with fluoride ions (LDH-F), used as filler, was prepared via ion exchange procedure and characterized by X-ray diffraction and FT-IR spectroscopy. The LDH-F inorganic particles (0.7, 5, 10, 20wt.%) were mixed with a photo-activated Bis-GMA/TEGDMA (45/55wt/wt) matrix and novel visible-light cured composites were prepared. The dynamic thermo-mechanical properties were determined by dynamic mechanical analyzer. The release of fluoride ions in physiological solution was determined using a ionometer. Total DNA content was measured by a PicoGreen dsDNA quantification kit to assess the proliferation rate of hDPSCs. Alkaline phosphatase activity (ALP) was measured in presence of fluoride resins. RESULTS: Incorporation of even small mass fractions (e.g. 0.7 and 5wt.%) of the fluoride LDH in Bis-GMA/TEGDMA dental resin significantly improved the mechanical properties of the pristine resin, in particular at 37 degrees C. The observed reinforcement increases on increasing the filler concentration. The release of fluoride ions resulted very slow, lasting months. ALP activity gradually increased for 28 days in hDPSCs cell grown, demonstrating that low concentrations of fluoride contributed to the cell differentiation. CONCLUSIONS: The prepared composites containing different amount of hydrotalcite filler showed improved mechanical properties, slow fluoride release and promoted hDPSCs cell proliferation and cell differentiation. PMID- 24239928 TI - Is hand-sewn anastomosis superior to stapled anastomosis following oesophagectomy? AB - A best evidence topic was written according to a structured protocol. The question addressed was: In patients undergoing oesophagectomy is stapled anastomosis (STA) superior to hand-sewn anastomosis (HSA) with respect to post operative outcomes. In total, 82 papers were found suitable using the reported search and 14 of these represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Existing evidence shows that STA is associated with reduced time to anastomotic construction and decreased intra operative blood loss but increased risk of benign stricture formation compared to HSA. There is no difference between HSA and STA with respect to cardiac or respiratory complications, anastomotic leakage, duration of hospital admission or 30-day mortality. In HSA, increasing surgical experience and intra-operative air leakage testing after anastomotic creation are associated with reduced risk of anastomotic leakage. Further adequately powered studies will enable identification of other local and systemic factors influencing anastomotic healing, which will lead to improved patient and anastomotic technique selection for optimal surgical outcomes. PMID- 24239927 TI - Achieving the desired colour in discoloured teeth, using leucite-based CAD-CAM laminate systems. AB - OBJECTIVES: To evaluate the cumulative effect of the abutment tooth and resin cement colour on the resultant optical properties of porcelain laminate veneers (PLVs) fabricated with leucite-based CAD/CAM blocks with different shades and thicknesses. METHODS: A total of 224 ceramic specimens were prepared from the IPS Empress CAD with four different shades of HT-A1, LT-A1, MT-A1 and Bl-1. Resin composite discs were prepared with shade A3.5. For the cementation, 4 different shades of light-cure resin cements were chosen. L*, a*, and b* values, as well as the chroma (C) and hue (h) values of each cemented ceramic and the A1 shade table, were recorded. RESULTS: L*, Cab* and hab* values of the cemented ceramics were influenced by ceramic shade, ceramic thickness, cement shade, and interaction terms of the three variables. There were significant differences between the 1-mm-thick ceramic veneers that exhibited higher L* and lower Cab* values compared with veneers that were 0.5mm in thickness. Using the Tr shade cement resulted in lower L* and higher Cab* values for all thicknesses and ceramic shades, whereas the WO shade cement resulted in higher values. CONCLUSIONS: The selected colour of a laminate restoration is significantly affected by the ceramic shade, ceramic thickness and resin cement shade. Using the WO shade resin cement seems to be more effective in masking the discoloured abutment tooth. Clinicians should also select the translucency level of the ceramic block with the shade when a leucite-based CAD/CAM system is chosen to treat a discoloured tooth. PMID- 24239929 TI - Folding mechanisms of periplasmic proteins. AB - More than one fifth of the proteins encoded by the genome of Escherichia coli are destined to the bacterial cell envelope. Over the past 20years, the mechanisms by which envelope proteins reach their three-dimensional structure have been intensively studied, leading to the discovery of an intricate network of periplasmic folding helpers whose members have distinct but complementary roles. For instance, the correct assembly of beta-barrel proteins containing disulfide bonds depends both on chaperones like SurA and Skp for transport across the periplasm and on protein folding catalysts like DsbA and DsbC for disulfide bond formation. In this review, we provide an overview of the current knowledge about the complex network of protein folding helpers present in the periplasm of E. coli and highlight the questions that remain unsolved. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID- 24239930 TI - Estrogen-dependent changes in estrogen receptor-beta mRNA expression in middle aged female rat brain. AB - During aging, estrogen production and circulating levels of estrogen are markedly decreased in females. Although several differences exist in the process of reproductive aging between women and female rats, the results of many studies suggest that the female rat, especially the middle-aged or aged ovariectomized female, is an important animal model of hormone loss in women. In target tissues including the brain, the actions of estrogen are mediated mainly via the alpha and beta subtypes of the estrogen receptor (ER-alpha and ER-beta). Estrogen treatment is known to change the expression of ER-alpha mRNA and protein in specific regions of the brain in middle-aged female rodents. In contrast, we do not know if estrogen regulates the expression of ER-beta in the brain at this stage of life. In the present study, we performed in situ hybridization on brain sections of ovariectomized and estrogen-treated middle-aged female rats to reveal the effects of estrogen on the expression of ER-beta throughout the brain. Our results showed that estrogen treatment decreased the number of ER-beta mRNA positive cells in the mitral cell and external plexiform layers of the olfactory bulb, central amygdaloid nucleus, medial geniculate nucleus, posterior hypothalamic nucleus, suprachiasmatic nucleus, and reticular part of the substantia nigra. As compared to the results of previous studies of young females, our data revealed that the regions in which expression of ER-beta mRNA expression is affected by estrogen differ in middle age. These results suggest that the effects of estrogen on ER-beta expression change with age. PMID- 24239931 TI - Intranasal oxytocin effects on social cognition: a critique. AB - The last decade has seen a large number of published findings supporting the hypothesis that intranasally delivered oxytocin (OT) can enhance the processing of social stimuli and regulate social emotion-related behaviors such as trust, memory, fidelity, and anxiety. The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an indirect peripheral mechanism. And third, the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior, there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not always "pro-social" and others suggest effects on social behaviors are due to a more general anxiolytic effect. In this critique, we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery, and to discuss intranasal OT effects on social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature. This article is part of a Special Issue entitled Oxytocin and Social Behav. PMID- 24239933 TI - Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats. AB - Progesterone and progestin receptors (PRs) are known to play a role in the development of brain physiology and behavior in many different species. The distribution and regulation of PRs within the developing brain suggest that they likely contribute to the organization of the brain and behavior in a sex-specific manner. We examined the role of PR signaling during development on the organization of adult sexual behavior and androgen receptor (AR) expression in the brain. We administered the PR antagonist, RU-486, subcutaneously to male and female rats on postnatal days 1-7 (0=day of birth) and examined adult sexual behavior and AR-immunoreactivity (AR-ir) in the adult brain. A typical sex difference in lordosis quotient (LQ) was observed and neonatal RU-486 treatment did not alter this behavior. In contrast, neonatal RU-486 treatment increased adult male sexual behavior and AR-ir in several brain areas in males. These data indicate that a transient disruption in PR signaling during development can have lasting consequences on the male brain and may increase male sexual behavior in part by increasing AR expression, and therefore androgen sensitivity, in adulthood. PMID- 24239934 TI - Analysis of neutral lipids from microalgae by HPLC-ELSD and APCI-MS/MS. AB - A method was developed to analyze neutral lipids through the use of three triglycerides, four free fatty acids, six di- and four mono-glycerides standards by high performance liquid chromatography (HPLC) normal phase coupled with either with evaporative light scattering detector (ELSD) or with mass spectrometry (MS) operating in atmospheric pressure chemical ionization (APCI) mode. The method was applied to the determination of the neutral lipid fraction from a Botryococcus braunii race A (B. braunii) culture. This method led us to identify neutral lipids synthesized by B. braunii in a single analysis within 45min through HPLC APCI-MS/MS technique. PMID- 24239936 TI - A high-throughput method for the simultaneous determination of multiple mycotoxins in human and laboratory animal biological fluids and tissues by PLE and HPLC-MS/MS. AB - A high-throughput method for the determination of 28 mycotoxins involving pressurised liquid extraction (PLE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been optimised and validated for determination in various biological fluids and tissues of human and laboratory animals. High throughput analysis was achieved using PLE pre-treatment and without the need for any cleanup. The extraction solvent was acetonitrile/water/acetic acid (80/19/1, v/v/v). The static extraction time was 5min. The extraction pressure and temperature were 1500psi and 140 degrees C, respectively. The flush volume was 60%. The limits of detection, which were defined as CCalpha, varied from 0.01MUg/kg (MUg/L) to 0.69MUg/kg (MUg/L). The recoveries of spiked samples from 0.20MUg/kg (MUg/L) to 2MUg/kg (MUg/L) ranged from 71% to 100.5% with relative standard deviations of less than 17.5%, except FB1 and FB2 recoveries, which were lower than 60%. The method was successfully applied in real samples, and the data indicate that this technique is a useful analytical method for the determination of mycotoxins from humans and animals. To the best of our knowledge, this method is the first for the large-scale testing of multi-class mycotoxins in all types of biological fluids and tissues that uses PLE and HPLC-MS/MS. PMID- 24239932 TI - Oxytocin and postpartum depression: delivering on what's known and what's not. AB - The role of oxytocin in the treatment of postpartum depression has been a topic of growing interest. This subject carries important implications, given that postpartum depression can have detrimental effects on both the mother and her infant, with lifelong consequences for infant socioemotional and cognitive development. In recent years, oxytocin has received attention for its potential role in many neuropsychiatric conditions beyond its well-described functions in childbirth and lactation. In the present review, we present available data on the clinical characteristics and neuroendocrine foundations of postpartum depression. We outline current treatment modalities and their limitations, and proceed to evaluate the potential role of oxytocin in the treatment of postpartum depression. The aim of the present review is twofold: (a) to bring together evidence from animal and human research concerning the role of oxytocin in postpartum depression, and (b) to highlight areas that deserve further research in order to bring a fuller understanding of oxytocin's therapeutic potential. This article is part of a Special Issue entitled Oxytocin and Social Behav. PMID- 24239937 TI - Cation exchange versus multimodal cation exchange resins for antibody capture from CHO supernatants: identification of contaminating host cell proteins by mass spectrometry. AB - We compared classical and multimodal cation exchange resins for the capture of recombinant antibodies from Chinese hamster ovary (CHO) cell culture supernatant. Both Capto S and Capto MMC resins present anionic groups while the multimodal Capto MMC also features a hydrophobic moiety. First we screened optimal binding and elution conditions in microplates with a pure antibody. We validated the results on the lab-scale with columns with a pure antibody and a CHO cell culture supernatant. Both resins achieved good yield and purity for the capture step of an antibody. However, the multimodal resin appeared more efficient and selective. Then we identified proteins in the antibody fraction by mass spectrometry in order to highlight the behavior of host cell proteins (HCPs). PMID- 24239935 TI - A novel uHPLC-MS/MS method for the quantitation of AZD7451 (AZ12607092) in human plasma. AB - Tropomyosin-related kinases (Trk) are tyrosine kinase receptors implicated in tumor proliferation, invasion, and survival signaling across a number of tumors, making them potentially attractive targets for the treatment of cancer. AZD7451 is a potent and selective inhibitor of Trk kinases currently undergoing a Phase I dose escalation in glioblastoma multiforme at the National Cancer Institute. A key part of early clinical testing for AZD7451 involves demonstrating that pharmacokinetic half-life and clinical exposures of AZD7451 are sufficient to inhibit Trk receptors in preclinical models. To address this need, an ultra sensitive analytical method was developed to measure the AZD7451 profile in human plasma. A liquid-liquid extraction recovered >80% of AZD7451 before quantitative analysis by ultra HPLC-MS/MS. A Varian Polaris((r)) C18-A column and a mass transition of m/z 383.5->340.5 (m/z 389.6->342.0 for the internal standard [(2)H6]-AZD7451) was used, and a dynamic calibration range of 0.5-1000ng/mL was established, which provided a sensitive (<8.5% deviation), and precise (<6%) quantitative assay for AZD7451. AZD7451 demonstrated stability in human plasma at room temperature for 24h (<7% change) and after extraction at 4 degrees C for 24h (<8% change), and was stable through 4 freeze/thaw cycles (<8% change). This method was used to measure AZD7451 plasma levels in clinical samples to confirm the sensitivity at several time points following AZD7451 treatment in subjects with glioblastoma. PMID- 24239938 TI - 'Smart' electronic operation notes in surgery: an innovative way to improve patient care. AB - AIMS: Operation notes are the only comprehensive account of what took place during surgery. Accurate and detailed documentation of surgical operation notes is crucial, both for post-operative management of patients and for medico-legal clarity. The aims of this study were to compare operation documentation against the Royal College of Surgeons of England guidelines and to compare the before-and after effect of introducing an electronic operation note system. METHODS: Fifty consecutive operation notes for inpatients that had undergone emergency orthopaedic trauma surgery were audited. An electronic operation note proforma was then introduced and a re-audit carried out after its implementation. RESULTS: The results after implementation of electronic operation notes, demonstrated a marked improvement. All notes contained an operation note (previously 5/6). Seventy five percent included time of surgery and age of patient (vs. 0% previously). A hundred percent included closure details and antibiotic selection at induction (vs. 60% and 69% respectively). Post-operative instructions improved to 100%. All were typed, making for 100% legibility as compared to only 66% of operation notes with legible hand writing in the initial audit. DISCUSSION/CONCLUSION: We used our pilot audit to target specific information that was commonly omitted and we 'enforced' these areas using drop-down selections in electronic operation note. This study has demonstrated that implementation of an electronic operation note system markedly improved the quality of documentation, both in terms of information detail and readability. We would recommend this template system as a standard for operation note documentation. PMID- 24239939 TI - Repair of nerve defect with chitosan graft supplemented by uncultured characterized stromal vascular fraction in streptozotocin induced diabetic rats. AB - Regenerative properties of stem cells at the service of nerve repair have been initiated during recent decades. Effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on peripheral nerve regeneration were studied using a rat sciatic nerve transection model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit filled with SVF. In control group, chitosan conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied 4 weeks, 8 weeks, and 12 weeks after surgery. In sham operated group, the sciatic nerve was only exposed and manipulated. Behavioral and Functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (P < 0.05). Gastrocnemius muscle mass in SVF transplanted animals was found to be significantly more than that in control group. Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers were significantly higher in SVF transplanted animals than in control group. In immunohistochemistry, location of reactions to S-100 in SVF transplanted animals was clearly more positive than that in control group. SVF transplantation combined with chitosan conduit could be considered as a readily accessible source of stromal cells that improve functional recovery of sciatic nerve. PMID- 24239940 TI - Exploring Leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) as a potential drug target by biochemical, biophysical and inhibition studies. AB - 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGR), an NADPH dependant enzyme catalyzes the synthesis of mevalonic acid from HMG-CoA required for isoprenoid biosynthesis. The HMGR gene from Leishmania donovani was cloned and expressed. Genome analysis of L. donovani revealed that HMGR gene having an open reading frame of 1305 bp encodes a putative protein of 434 amino acids. LdHMGR showed optimal activity at pH 7.2 and temperature 37 degrees C. Kinetic analysis of this enzyme revealed Km values of 35.7 +/- 2.5 MUM for (R,S)-HMG-CoA and 70 +/ 7.9 MUM for the cofactor NADPH. On tryptophan fluorescence quenching, the Stern Volmer constant (Ksv), binding constant (Ka) and protein:cofactor stoichiometry for interaction of NADPH cofactor with the enzyme were found to be 6.0 +/- 0.7 M( 1), 0.17 MUM and 0.72 respectively. Polyclonal anti-rat HMGR antibody detected a band of ~45 kDa in all phases of promastigote growth. Biophysical analysis of the secondary structure of LdHMGR confirmed the presence of 25.7 +/- 0.35% alpha helicity. Thermal denaturation studies showed extreme stability of the enzyme with 60% helical structure retained at 90 degrees C. Statins (simvastatin and atorvastatin) and non-statin (resveratrol) effectively inhibited the growth of L. donovani promastigotes as well as the catalytic activity of the recombinant LdHMGR. Atorvastatin was found to be most potent antileishmanial inhibitor with an IC50 value of 19.4 +/- 3.07 MUM and a very lower concentration of 315.5 +/- 2.1 nM was enough to cause 50% recombinant LdHMGR enzyme inhibition suggesting direct interaction with the rate limiting enzyme of the ergosterol biosynthetic pathway. Exogenous supplementation of ergosterol in case of atorvastatin and resveratrol treated cells caused complete reversal of growth inhibition whereas simvastatin was found to be ergosterol refractory. Cholesterol supplementation however, failed to overcome growth inhibition in all the cases. Overall our study emphasizes on exploring LdHMGR as a potential drug target for the development of novel antileishmanial agents. PMID- 24239941 TI - Cholera toxin expression by El Tor Vibrio cholerae in shallow culture growth conditions. AB - Vibrio cholerae O1 classical, El Tor and O139 are the primary biotypes that cause epidemic cholera, and they also express cholera toxin (CT). Although classical V. cholerae produces CT in various settings, the El Tor and O139 strains require specific growth conditions for CT induction, such as the so-called AKI conditions, which consist of growth in static conditions followed by growth under aerobic shaking conditions. However, our group has demonstrated that CT production may also take place in shallow static cultures. How these type of cultures induce CT production has been unclear, but we now report that in shallow culture growth conditions, there is virtual depletion of dissolved oxygen after 2.5 h of growth. Concurrently, during the first three to 4 h, endogenous CO2 accumulates in the media and the pH decreases. These findings may explain CT expression at the molecular level because CT production relies on a regulatory cascade, in which the key regulator AphB may be activated by anaerobiosis and by low pH. AphB activation stimulates TcpP synthesis, which induces ToxT production, and ToxT directly stimulates ctxAB expression, which encodes CT. Importantly, ToxT activity is enhanced by bicarbonate. Therefore, we suggest that in shallow cultures, AphB is activated by initial decreases in oxygen and pH, and subsequently, ToxT is activated by intracellular bicarbonate that has been generated from endogenous CO2. This working model would explain CT production in shallow cultures and, possibly, also in other growth conditions. PMID- 24239942 TI - US trade agreement threatens to increase drug prices and withhold safety data. PMID- 24239943 TI - Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study. AB - OBJECTIVES: The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD. DESIGN: This study included 975 participants (324 men, mean age of 67.2 years; 651 women, mean age of 66.0 years) with an age range of 21-97 years in the Wakayama Spine Study. DD on MRI was classified into Pfirrmann's system (grades 4 and 5 indicating DD). We assessed the prevalence of DD at each level in the cervical, thoracic, and lumbar regions and the entire spine, and examined DD-associated factors and symptoms. RESULTS: The prevalence of DD over the entire spine was 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6 (men: 51.5%, women: 46%), T6/7 (men: 32.4%, women: 37.7%), and L4/5 (men: 69.1%, women: 75.8%). Age and obesity were associated with the presence of DD in all regions. Low back pain was associated with the presence of DD in the lumbar region. CONCLUSION: The current study established the baseline data of DD over the entire spine in a large population of elderly individuals. These data provide the foundation for elucidating the causes and mechanisms of DD. PMID- 24239944 TI - Eukaryotic ribosomal protein S3: A constituent of translational machinery and an extraribosomal player in various cellular processes. AB - Ribosomal proteins from the S3 family are universal components of small ribosomal subunits in all three domains of life. In eukaryotes, ribosomal protein S3e (rpS3e) is one of 33 proteins of small subunit of the ribosome. It functions not only within the ribosome participating in translation but also as an extraribosomal player involved in a number of vitally important cellular events. RpS3e is directly implicated in translation initiation via participation in rearrangements of the small subunit structure occurring upon the binding of initiation factors eIF1 and eIF1A, which opens the ribosomal mRNA binding channel for incoming mRNA and allows scanning. Being located at the mRNA entry site of the ribosome, rpS3e is suggested to interact with mRNA part downstream of the codon at the decoding site and it could be implicated in helicase activity of the ribosome by analogy to its bacterial counterpart rpS3p. Extraribosomal functions of rpS3e are mainly based on its ability to bind to nucleic acids, although protein-protein interactions take place too. As an independent player, rpS3e is involved in DNA repair, selective gene regulation via implication in NF-kappaB signaling pathway, inducing apoptosis, control of expression of the own gene at the translation level and molecular interactions affecting half-life of the protein. Involvement of rpS3e in various cellular processes is mediated by specific mechanisms utilizing post-translational modifications of the protein. Here, we present accumulated to date information and current ideas concerning functions of rpS3e as a constituent of translational machinery and of the free protein as a key player in various events of the cell life. PMID- 24239946 TI - Drying of Cryptosporidium oocysts and Giardia cysts to slides abrogates use of vital dyes for viability staining. AB - Vital dye staining has long been used to assess viability of Cryptosporidium oocysts and Giardia cysts, with staining and enumeration in suspension. Some recent studies, however, have dried samples to microscope slides prior to staining. Here we demonstrate that this approach may considerably underestimate parasite viability in the original sample. PMID- 24239945 TI - Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress. AB - Cisplatin, a cancer chemotherapy drug, is nephrotoxic. The aim of this study was to investigate whether resveratrol (RES) reduced cisplatin cytotoxicity and oxidative stress. Rat renal cortical slices were pre-incubated 30min with 0 (VEH, ethanol) or 30MUg/ml RES followed by 60, 90 or 120min co-incubation with 0, 75, or 150MUg/ml cisplatin. Lactate dehydrogenase (LDH) leakage was unchanged at 60 and 90min by cisplatin. Cisplatin increased (p<0.05) LDH leakage at 120min which was protected by RES. Cisplatin induced oxidative stress prior to LDH leakage as cisplatin depressed glutathione peroxidase and superoxide dismutase (SOD) activity, increased lipid peroxidation, protein carbonyls and 4-hydroxynonenal (4 HNE) adducted proteins within 60min. RES failed to reverse glutathione (GSH) depression by cisplatin. In order to eliminated an extracellular interaction between RES and cisplatin, additional studies (RINSE studies) allowed a 30min RES uptake into slices, transfer of slices to buffer lacking RES, followed by 120min cisplatin incubation. RES in the RINSE studies prevented LDH leakage by cisplatin indicating that RES protection was not via a physical interaction with cisplatin in the media. These findings indicate that RES diminished cisplatin in vitro renal toxicity and prevented the development of oxidative stress. PMID- 24239947 TI - Insights into eukaryotic primer synthesis from structures of the p48 subunit of human DNA primase. AB - DNA replication in all organisms requires polymerases to synthesize copies of the genome. DNA polymerases are unable to function on a bare template and require a primer. Primases are crucial RNA polymerases that perform the initial de novo synthesis, generating the first 8-10 nucleotides of the primer. Although structures of archaeal and bacterial primases have provided insights into general priming mechanisms, these proteins are not well conserved with heterodimeric (p48/p58) primases in eukaryotes. Here, we present X-ray crystal structures of the catalytic engine of a eukaryotic primase, which is contained in the p48 subunit. The structures of p48 reveal that eukaryotic primases maintain the conserved catalytic prim fold domain, but with a unique subdomain not found in the archaeal and bacterial primases. Calorimetry experiments reveal that Mn(2+) but not Mg(2+) significantly enhances the binding of nucleotide to primase, which correlates with higher catalytic efficiency in vitro. The structure of p48 with bound UTP and Mn(2+) provides insights into the mechanism of nucleotide synthesis by primase. Substitution of conserved residues involved in either metal or nucleotide binding alter nucleotide binding affinities, and yeast strains containing the corresponding Pri1p substitutions are not viable. Our results reveal that two residues (S160 and H166) in direct contact with the nucleotide were previously unrecognized as critical to the human primase active site. Comparing p48 structures to those of similar polymerases in different states of action suggests changes that would be required to attain a catalytically competent conformation capable of initiating dinucleotide synthesis. PMID- 24239948 TI - Destabilization of the homotetrameric assembly of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from the hyperthermophile Pyrococcus furiosus enhances enzymatic activity. AB - Many proteins adopt homomeric quaternary structures to support their biological function, including the first enzyme of the shikimate pathway that is ultimately responsible for the biosynthesis of the aromatic amino acids in plants and microorganisms. This enzyme, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAH7PS), adopts a variety of different quaternary structures depending on the organism in which it is found. The DAH7PS from the hyperthermophilic archaebacterium Pyrococcus furiosus was previously shown to be tetrameric in its crystalline form, and this quaternary association is confirmed in an improved structure in a different crystal system. This tetramer is also present in solution as revealed by small-angle X-ray scattering and analytical ultracentrifugation. This homotetrameric form has two distinct interfaces, both of which bury over 10% each of the surface area of a single monomer. Substitution of Ile for Asp in the hydrophobic region of one interface gives a protein with a remarkable 4-fold higher maximum catalytic rate than the wild-type enzyme. Analytical ultracentrifugation at pH7.5 reveals that the tetrameric form is destabilized; although the protein crystallizes as a tetramer, equilibrium exists between tetrameric and dimeric forms with a dissociation constant of 22 MUM. Thus, under the conditions of kinetic assay, the enzyme is primarily dimeric, revealing that the dimeric form is a fully functional catalyst. However, in comparison to the wild-type protein, the thermal stability of the dimeric protein is significantly compromised. Thus, an unusual compromise of enzymatic activity versus stability is observed for this DAH7PS from an organism that favors a hyperthermophilic environment. PMID- 24239949 TI - The structure of TAX1BP1 UBZ1+2 provides insight into target specificity and adaptability. AB - TAX1BP1 is a novel ubiquitin-binding adaptor protein involved in the negative regulation of the NF-kappaB transcription factor, which is a key player in inflammatory responses, immunity and tumorigenesis. TAX1BP1 recruits A20 to the ubiquitinated signaling proteins TRAF6 and RIP1, leading to their A20-mediated deubiquitination and the disruption of IL-1-induced and TNF-induced NF-kappaB signaling, respectively. The two zinc fingers localized at its C-terminus function as novel ubiquitin-binding domains (UBZ, ubiquitin-binding zinc finger). Here we present for the first time both the solution and crystal structures of two classical UBZ domains in tandem within the human TAX1BP1. The relative orientation of the two domains is slightly different in the X-ray structure with respect to the NMR structure, indicating some degree of conformational flexibility, which is rationalized by NMR relaxation data. The observed degree of flexibility and stability between the two UBZ domains might have consequences on the recognition mechanism of interacting partners. PMID- 24239950 TI - Oesophageal atresia with tracheoesophageal fistula and anal atresia in a patient with a de novo microduplication in 17q12. AB - Oesophageal atresia (OA) and tracheoesophageal fistula (TOF) are foregut malformations with a heterogeneous etiology. OA/TOF may occur as an isolated anomaly or as part of a syndrome. Chromosomal anomalies have been reported in 6 10% of OA/TOF. Several genes have been implicated in cases of syndromic OA/TOF, but no single specific chromosomal and monogenic defect has been confirmed as a main etiological factor. We described a patient with a 1.4 Mb duplication at 17q12 detected by SNP-array study and validated using qRT-PCR, who presented with an oesophageal atresia accompanied with tracheoesophageal fistula and anal atresia as well as other symptoms resembling VATER association (thumb hypoplasia, sacral bone defect, cryptorchidism). Genomic rearrangements of chromosome 17q12 are associated with a variety of clinical phenotypes. Only few cases with OA patients with the duplication in 17q12 have been reported. The 17q12 region comprised 15 genes. We propose to consider a role for selected genes such as AATF (cell proliferation and apoptosis) and TADA2L (Wnt pathway) at the 17q12 region as well as developmental and transcriptional pathways represented by these genes, in the development of OA/TOF and VATER association. PMID- 24239951 TI - Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases. AB - BACKGROUND: 15q11-q13 region is an area of well-known susceptibility to genomic rearrangements, in which several breakpoints have been identified (BP1-BP5). Duplication of this region is observed in two instances: presence of a supernumerary marker chromosome (SMC) derived of chromosome 15, or interstitial tandem duplication. Duplications are clinically characterized by a variable phenotype that includes central hypotonia, developmental delay, speech delay, seizure, minor dysmorphic features and autism. METHODS: Retrospective clinical and molecular study of 30 unrelated patients who were identified among the patients seen at the genetic clinics of Robert DEBRE hospital with microduplication of the 15q11-q13 region. RESULTS: Fifteen patients presented with a supernumerary marker derived from chromosome 15. In fourteen cases the SMC was of large size, encompassing the Prader-Willi/Angelman critical region. All but one was maternal in origin. One patient had a PWS-like phenotype in absence of maternal UPD. In one case, the marker had a smaller size and contained only the BP1-BP2 region. Fifteen patients presented with interstitial duplication. Four cases were inherited from phenotypically normal parents (3 maternal and 1 paternal). Phenotypic features were somewhat variable and 57% presented with autism. Twelve patients showed cerebral anomalies and 18 patients had an abnormal EEG with a typical, recognizable pattern of excessive diffuse rapid spikes in the waking record, similar to the pattern observed after benzodiazepine exposure. Duplication of paternally expressed genes MKRN3, MAGEL2 and NDN in two autistic patients without extra material of a neighboring region enhances their likelihood to be genes related to autism. PMID- 24239952 TI - Exercise training can induce cardiac autophagy at end-stage chronic conditions: insights from a graft-versus-host-disease mouse model. AB - INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is a frequent cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo HSCT), and severely compromises patients' physical capacity. Despite the aggressive nature of the disease, aerobic exercise training can positively impact survival as well as clinical and functional parameters. We analyzed potential mechanisms underlying the recently reported cardiac function improvement in an exercise-trained cGVHD murine model receiving lethal total body irradiation and immunosuppressant treatment (Fiuza-Luces et al., 2013. Med Sci Sports Exerc 45, 1703-1711). We hypothesized that a cellular quality-control mechanism that is receiving growing attention in biomedicine, autophagy, was involved in such improvement. METHODS: BALB/C female mice (aged 8wk) with cGVHD were randomly assigned to a control/exercise group (n=12/11); the exercise group underwent moderate-intensity treadmill training during 11wk after allo-HSCT. In the hearts of those few mice surviving the entire 11wk period (n=2/5), we studied molecular markers of: macroautophagy induction, preservation of contractile/structural proteins, oxidative capacity, oxidative stress, antioxidant defense, and mitochondrial dynamics. RESULTS: Mainly, exercise training increased the myocardial content of the macroautophagy markers LC3BII, Atg12, SQSTM1/p62 and phospho-ULK1 (S555), as well as of alpha-tubuline, catalase and glutathione reductase (all p<0.05). CONCLUSIONS: Our results suggest that exercise training elicits a positive autophagic adaptation in the myocardium that may help preserve cardiac function even at the end-stage of a devastating disease like cGVHD. These preliminary findings might provide new insights into the cardiac exercise benefits in chronic/debilitating conditions. PMID- 24239953 TI - Self-compassion as a predictor of interleukin-6 response to acute psychosocial stress. AB - We examined the hypothesis that self-compassion is associated with lower levels of stress-induced inflammation. On two consecutive days, plasma concentrations of interleukin-6 (IL-6) were assessed at baseline and at 30 and 120 min following exposure to a standardized laboratory stressor in a sample of 41 healthy young adults. Participants who were higher in self-compassion exhibited significantly lower day 1 IL-6 responses, even when controlling for self-esteem, depressive symptoms, demographic factors, and distress. Self-compassion was not related to day 2 IL-6 response but was inversely related to day 2 baseline IL-6 levels, and to increase in baseline IL-6 from day 1 to day 2. These findings suggest that self-compassion may serve as a protective factor against stress-induced inflammation and inflammation-related disease. PMID- 24239954 TI - Pulmonary production of osteopontin in humans: effects of left ventricular systolic dysfunction and cardiopulmonary bypass. AB - BACKGROUND: We evaluated pulmonary production of osteopontin (OPN) in left ventricular systolic dysfunction (LVSD) and after cardiopulmonary bypass surgery (CPB). OPN is a phosphoglycoprotein involved in inflammation and remodeling. In subjects with LVSD, plasma OPN correlates with prognosis but its origin is unknown. We hypothesized that the lungs produce OPN and that this could be affected by LVSD and CPB. METHODS AND RESULTS: Subjects with (n = 57; left ventricular ejection fraction [LVEF] 32 +/- 8%) and without (n = 63; LVEF 59 +/- 7%) LVSD were studied during CPB. Arterial and venous OPN plasma levels were determined. Arterial and venous OPN levels were higher in LVSD (P = .0290). For both groups, levels dropped 1 hour after surgery and nearly doubled 24 hours after (P < .0001 vs basal). Notably, there was a significant positive arteriovenous gradient with arterial levels higher than venous levels. Arteriovenous differences were statistically significant at baseline (P = .0120) and 1 hour (P < .0001) but not at 24 hours (P = .0649). Arterial levels in heart failure correlated inversely with renal function (P = .016) and positively with mean pulmonary pressure (P = .028), heart rate (P = .036), and C-reactive protein (P = .047). CONCLUSIONS: There is production of circulating OPN by the lungs, unaffected by LVSD or CPB. This likely represents an overflow from local lung production and does not contribute to increased levels in LVSD or after CPB. PMID- 24239955 TI - Heart failure therapy-induced early ST2 changes may offer long-term therapy guidance. AB - BACKGROUND: Biomarkers may help to monitor and tailor treatment in patients with acute heart failure (AHF). METHODS AND RESULTS: Levels of ST2, a novel biomarker integrating hypervolemic cardiac strain and proinflammatory signals, were measured at presentation to the emergency department (ED) and after 48 hours in 207 patients with AHF. Patients were stratified according to their early ST2 response (responders: ST2 decrease >=25%; nonresponders: ST2 decrease <25%) and beta-blocker, renin-angiotensin-aldosterone system (RAAS) blockade, or diuretic treatment status at hospital discharge. We assessed the utility of ST2 levels and its changes to predict long-term mortality and the interaction between ST2 levels, treatment at discharge, and 1-year mortality. ST2 levels were higher in nonsurvivors than in survivors (median 108 vs 69 ng/mL; P < .01) and decreased significantly during the 1st 48 hours (median decrease 33%). ST2 decrease was less in nonsurvivors compared with survivors (median -25% vs -42%; P < .01). In Cox regression, early ST2 changes independently predicted 1-year mortality (hazard ratio 1.07 for every increase of 10%; P = .02). RAAS blockers at discharge were associated with survival independently from ST2 response, whereas the association of beta-blockers with survival differed markedly according to ST2 response, with beneficial effects restricted to ST2 nonresponders (P interaction = .04). A similar, albeit nonsignificant, trend was observed for diuretics (P interaction = .11). CONCLUSIONS: ED and serial ST2 measurements are independent predictors of 1-year mortality in AHF. PMID- 24239956 TI - Plasma concentrations of sAxl are associated with severe preeclampsia. AB - OBJECTIVE: Preeclampsia, a multisystem disorder unique to pregnancy, is a major cause of maternal and perinatal mortality and morbidity. Inadequate trophoblast invasion and vascular dysfunction are believed to be involved in preeclampsia. Axl, which interacts with its ligand Gas6, known to regulate cell migration, adhesion, and vascular angiogenesis or homeostasis and vascular network formation, may be implicated in preeclampsia, as preeclampsia is a specific vascular disease. sAxl, a soluble form of Axl, is bound to Gas6 in plasma, which inhibits the activation of the Axl-Gas6 pathway. The aim of this study was to determine the changes and significance of plasma concentrations of sAxl in severe preeclampsia, as well as its correlation with the clinical parameters of severe preeclampsia. DESIGN AND METHODS: Fifty-eight women with severe preeclampsia and 31 healthy pregnant women were included in the study, from April 2012 to October 2012. Plasma sAxl concentrations were detected with an immunosorbent assay (ELISA) kit. RESULTS: Plasma sAxl concentrations were significantly higher in the preeclampsia group (61.52+/-17.57ng/mL) than in the normal pregnancy group (45.29+/-15.44ng/mL) (P<0.05). Plasma sAxl concentrations in the severe preeclampsia patients correlated positively with systolic and diastolic blood pressures (r=0.628, P<0.05 vs. r=0.394, P<0.05, respectively) and proteinuria (r=0.583, P<0.05), but inversely with plasma albumin (r=-0.444, P<0.05), gestation of delivery (r=-0.554, P<0.05), and birth weight (r=-0.476, P<0.05). Multiple linear regression analysis indicated that systolic blood pressure and proteinuria were influence factors of plasma sAxl levels (beta1=0.520, P<0.05; beta2=0.461, P<0.05). CONCLUSIONS: Plasma sAxl concentrations were higher in the preeclampsia patients, and plasma sAxl levels were correlated with the clinical parameters of severe preeclampsia. Furthermore, systolic blood pressure and proteinuria might be influence factors of plasma sAxl level. PMID- 24239957 TI - Electroencephalographic field influence on calcium momentum waves. AB - Macroscopic electroencephalographic (EEG) fields can be an explicit top-down neocortical mechanism that directly drives bottom-up processes that describe memory, attention, and other neuronal processes. The top-down mechanism considered is macrocolumnar EEG firings in neocortex, as described by a statistical mechanics of neocortical interactions (SMNI), developed as a magnetic vector potential A. The bottom-up process considered is Ca(2+) waves prominent in synaptic and extracellular processes that are considered to greatly influence neuronal firings. Here, the complimentary effects are considered, i.e., the influence of A on Ca(2+) momentum, p. The canonical momentum of a charged particle in an electromagnetic field, Pi=p+qA (SI units), is calculated, where the charge of Ca(2+) is q=-2e, e is the magnitude of the charge of an electron. Calculations demonstrate that macroscopic EEG A can be quite influential on the momentum p of Ca(2+) ions, in both classical and quantum mechanics. Molecular scales of Ca(2+) wave dynamics are coupled with A fields developed at macroscopic regional scales measured by coherent neuronal firing activity measured by scalp EEG. The project has three main aspects: fitting A models to EEG data as reported here, building tripartite models to develop A models, and studying long coherence times of Ca(2+) waves in the presence of A due to coherent neuronal firings measured by scalp EEG. The SMNI model supports a mechanism wherein the p+qA interaction at tripartite synapses, via a dynamic centering mechanism (DCM) to control background synaptic activity, acts to maintain short-term memory (STM) during states of selective attention. PMID- 24239958 TI - N-player mosquito net game: individual and social rationality in the misuse of insecticide-treated nets. AB - Many governmental and non-governmental organizations have distributed insecticide treated nets (ITNs) to malaria endemic areas, which contributed to the reduction of malaria deaths. However, some people in malaria endemic areas used ITNs for alternative purposes such as fishery and agriculture. It is unclear why people threatened by malaria misuse ITNs. Here we develop a N-player mosquito net game, and theoretically show that the misuse of ITNs might be underpinned by individual and social rationality. In the mosquito net game, each player uses ITNs for malaria prevention or alternative purposes. The proper ITN use decreases the probability of malaria infection, while the improper ITN use increases the player's labor productivity. Each player's expected payoff is influenced by other players' strategies. We found that the misuse of ITNs can be a Pareto efficient Nash equilibrium. The maximum number of players using ITNs for malaria prevention is limited by insecticidal effectiveness of ITNs and extra income from ITN misuse. Furthermore, we found that players in a low-income community are attracted to the misuse of ITNs even if the probability of malaria infection is high. Introduction of a tax on ITN misuse was shown to be effective to motivate the players to use ITNs for malaria prevention. Our results demonstrate that understanding decision making of people in malaria endemic areas is essential to design more effective malaria control programs. PMID- 24239959 TI - Influence of the molybdenum cofactor biosynthesis on anaerobic respiration, biofilm formation and motility in Burkholderia thailandensis. AB - Burkholderia thailandensis is closely related to Burkholderia pseudomallei, a bacterial pathogen and the causative agent of melioidosis. B. pseudomallei can survive and persist within a hypoxic environment for up to one year and has been shown to grow anaerobically in the presence of nitrate. Currently, little is known about the role of anaerobic respiration in pathogenesis of melioidosis. Using B. thailandensis as a model, a library of 1344 transposon mutants was created to identify genes required for anaerobic nitrate respiration. One transposon mutant (CA01) was identified with an insertion in BTH_I1704 (moeA), a gene required for the molybdopterin biosynthetic pathway. This pathway is involved in the synthesis of a molybdopterin cofactor required for a variety of molybdoenzymes, including nitrate reductase. Disruption of molybdopterin biosynthesis prevented growth under anaerobic conditions, when using nitrate as the sole terminal electron acceptor. Defects in anaerobic respiration, nitrate reduction, motility and biofilm formation were observed for CA01. Mutant complementation with pDA-17:BTH_I1704 was able to restore anaerobic growth on nitrate, nitrate reductase activity and biofilm formation, but did not restore motility. This study highlights the potential importance of molybdoenzyme dependent anaerobic respiration in the survival and virulence of B. thailandensis. PMID- 24239960 TI - The dynamics of peptidoglycan structure and function: conference report on the 3rd Great Wall Symposium. PMID- 24239961 TI - Immunity to the Staphylococcus aureus leaderless four-peptide bacteriocin aureocin A70 is conferred by AurI, an integral membrane protein. AB - Aureocin A70, which is produced by Staphylococcus aureus A70, is the only four component bacteriocin described thus far. The genetic determinants responsible for its production are arranged as three transcriptional units encoded by the 7.9 kb plasmid pRJ6. While the transcriptional unit formed by the genes aurABCD encodes the bacteriocin structural peptides, a second divergent gene, aurT, codes for an ABC transporter involved in bacteriocin externalization. The third transcriptional unit is composed of two genes, orfAB, whose functions were hitherto unknown. RT-PCR analysis of orfAB expression revealed that they are arranged as an operon. When orfAB, either with or without the transcriptional terminator found downstream of orfB, was expressed in two different S. aureus strains sensitive to aureocin A70, all strains became immune to this bacteriocin. Cloning of orfB alone, with or without the transcriptional terminator, confirmed orfB participation in immunity, although full immunity was not observed. An increase in immunity was achieved when two copies of orfB were cloned oriented with the exogenous Plac promoter present in the expression vector pT181mcs. orfB (here referred to as aurI) was shown to be responsible for aureocin A70 immunity, but the full immunity phenotype seems to depend on translational coupling involving orfA, which encodes a putative transcriptional regulator, and aurI. PMID- 24239962 TI - Role of Salmonella Typhimurium small RNAs RyhB-1 and RyhB-2 in the oxidative stress response. AB - As part of the response to specific stress conditions, bacteria express small molecules of non-coding RNA which maintain cellular homeostasis by regulating gene expression, commonly at the post-transcriptional level. Among these, in Salmonella enterica sv. Typhimurium, the paralog small non-coding RNAs RyhB-1 and RyhB-2 play an important role in iron homeostasis. In addition, in the present work, we show that RyhB-1 and RyhB-2 also participate in the response to hydrogen peroxide (H2O2). Deletion of RyhB-1 and/or RyhB-2 resulted in increased levels of intracellular reactive oxygen species, protein carbonylation and an altered NADH/NAD(+) ratio. Analyses of the transcriptional profiles of ryhB-1 and ryhB-2 by northern blot and qRT-PCR showed that they are induced in response to H2O2 in an OxyR-dependent manner. By using lacZ-fusions and electrophoretic mobility shift assays, we confirmed the requirement of OxyR for inducing expression of both ryhB-1 and ryhB-2. Taken together, our results support a model in which, in response to peroxide treatment, ryhB-1 and ryhB-2 are upregulated by OxyR through direct interaction with their promoter region. PMID- 24239963 TI - Novel markers of osteogenic and adipogenic differentiation of human bone marrow stromal cells identified using a quantitative proteomics approach. AB - Today, the tool that is most commonly used to evaluate the osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro is the demonstration of the expression of multiple relevant markers, such as ALP, RUNX2 and OCN. However, as yet, there is no single surface marker or panel of markers which clearly defines human BMSCs (hBMSCs) differentiating towards the osteogenic lineage. The aim of this study was therefore to examine this issue. Stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics was utilized to investigate differently expressed surface markers in osteogenically differentiated and undifferentiated hBMSCs. Labeled membrane proteins were analyzed by mass spectrometry (MS) and 52 proteins with an expression ratio above 2, between osteogenically differentiated and undifferentiated cells, were identified. Subsequent validation, by flow cytometry and ELISA, of the SILAC expression ratios for a number of these proteins and investigations of the lineage specificity of three candidate markers were performed. The surface markers, CD10 and CD92, demonstrated significantly increased expression in hBMSCs differentiated towards the osteogenic and adipogenic lineages. In addition, there was a slight increase in CD10 expression during chondrogenic differentiation. Furthermore, the expression of the intracellular protein, crystalline-alphaB (CRYaB), was only significantly increased in osteogenically differentiated hBMSCs and not affected during differentiation towards the chondrogenic or adipogenic lineages. It has been concluded from the present results that CD10 and CD92 are potential markers of osteogenic and adipogenic differentiation and that CRYaB is a potential novel osteogenic marker specifically expressed during the osteogenic differentiation of hBMSCs in vitro. PMID- 24239964 TI - Efficient definitive endoderm induction from mouse embryonic stem cell adherent cultures: a rapid screening model for differentiation studies. AB - Definitive endoderm (DE) differentiation from mouse embryonic stem cell (mESC) monolayer cultures has been limited by poor cell survival or low efficiency. Recently, a combination of TGFbeta and Wnt activation with BMP inhibition improved DE induction in embryoid bodies cultured in suspension. Based on these observations we developed a protocol to efficiently induce DE cells in monolayer cultures of mESCs. We obtained a good cell yield with 54.92% DE induction as shown by Foxa2, Sox17, Cxcr4 and E-Cadherin expression. These DE-cells could be further differentiated into posterior foregut and pancreatic phenotypes using a culture protocol initially developed for human embryonic stem cell (hESC) differentiation. In addition, this mESC-derived DE gave rise to hepatocyte-like cells after exposure to BMP and FGF ligands. Our data therefore indicate a substantial improvement of monolayer DE induction from mESCs and support the concept that differentiation conditions for mESC-derived DE are similar to those for hESCs. As mESCs are easier to maintain and manipulate in culture compared to hESCs, and considering the shorter duration of embryonic development in the mouse, this method of efficient DE induction on monolayer will promote the development of new differentiation protocols to obtain DE-derivatives, like pancreatic beta-cells, for future use in cell replacement therapies. PMID- 24239965 TI - A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment. AB - In vitro stimulation of HSCs with growth factors generally leads to their depletion. Understanding the molecular mechanisms underlying expansion of HSCs in vivo following myeloablation could lead to successful expansion of HSCs ex vivo for therapeutic purposes. Current findings show that mTORC1 is activated in HSPCs following 5-fluorouracil treatment and that mTORC1 activation is dependent on mitochondrial ETC capacity of HSPCs. Moreover, expression of PGC-1 family members, proteins that regulate mitochondrial biogenesis, in HSPCs following 5 fluorouracil treatment changes; also, these proteins play a stage specific role in hematopoietic recovery. While PRC regulates HSCs' expansion during early recovery phase, PGC-1alpha regulates progenitor cell proliferation and recovery of hematopoiesis during later phase. During early recovery phase, PRC expression, mitochondrial activity and mTORC1 activation are relatively higher in PGC-1alpha( /-) HSCs compared to WT HSCs, and PGC-1alpha(-/-) HSCs show greater expansion. Administration of rapamycin, but not NAC, during early recovery phase improves WT HSC numbers but decreases PGC-1alpha(-/-) HSC numbers. The current findings demonstrate that mTOR activation can increase HSC numbers provided that the energy demand created by mTOR activation is successfully met. Thus, critical tuning between mTORC1 activation and mitochondrial ETC capacity is crucial for HSC maintenance/expansion in response to mitogenic stimulation. PMID- 24239966 TI - Miniaturized passive hydrogel check valve for hydrocephalus treatment. AB - Improvements in cerebrospinal fluid (CSF) draining techniques for treatment of hydrocephalus are urgently sought after to substitute for current CSF shunts that are plagued by high failure rates. The passive check valve aims to restore near natural CSF draining operations while mitigating possible failure mechanisms caused by finite leakage or low resilience that frequently constrain practical implementation of miniaturized valves. A simple hydrogel diaphragm structures core passive valve operations and enforce valve sealing properties to substantially lower reverse flow leakage. Experimental measurements demonstrate realization of targeted cracking pressures (PT ~ 20-110 mmH2O) and operation at 800 <; DeltaP <; 600 mmH2O without observable degradation or leakage. PMID- 24239967 TI - Maximum-likelihood estimation for indicator dilution analysis. AB - Indicator-dilution methods are widely used by many medical imaging techniques and by dye-, lithium-, and thermodilution measurements. The measured indicator dilution curves are typically fitted by a mathematical model to estimate the hemodynamic parameters of interest. This paper presents a new maximum-likelihood algorithm for parameter estimation, where indicator dilution curves are considered as the histogram of underlying transit-time distribution. Apart from a general description of the algorithm, semianalytical solutions are provided for three well-known indicator dilution models. An adaptation of the algorithm is also introduced to cope with indicator recirculation. In simulations as well as in experimental data obtained by dynamic contrast-enhanced ultrasound imaging, the proposed algorithm shows a superior parameter estimation accuracy over nonlinear least-squares regression. The feasibility of the algorithm for use in vivo is evaluated using dynamic contrast-enhanced ultrasound recordings obtained with the purpose of prostate cancer detection. The proposed algorithm shows an improved ability (increase in receiver-operating characteristic curve area of up to 0.13) with respect to existing methods to differentiate between healthy tissue and cancer. PMID- 24239968 TI - Detection of life-threatening arrhythmias using feature selection and support vector machines. AB - Early detection of ventricular fibrillation (VF) and rapid ventricular tachycardia (VT) is crucial for the success of the defibrillation therapy. A wide variety of detection algorithms have been proposed based on temporal, spectral, or complexity parameters extracted from the ECG. However, these algorithms are mostly constructed by considering each parameter individually. In this study, we present a novel life-threatening arrhythmias detection algorithm that combines a number of previously proposed ECG parameters by using support vector machines classifiers. A total of 13 parameters were computed accounting for temporal (morphological), spectral, and complexity features of the ECG signal. A filter type feature selection (FS) procedure was proposed to analyze the relevance of the computed parameters and how they affect the detection performance. The proposed methodology was evaluated in two different binary detection scenarios: shockable (FV plus VT) versus nonshockable arrhythmias, and VF versus nonVF rhythms, using the information contained in the medical imaging technology database, the Creighton University ventricular tachycardia database, and the ventricular arrhythmia database. sensitivity (SE) and specificity (SP) analysis on the out of sample test data showed values of SE=95%, SP=99%, and SE=92% , SP=97% in the case of shockable and VF scenarios, respectively. Our algorithm was benchmarked against individual detection schemes, significantly improving their performance. Our results demonstrate that the combination of ECG parameters using statistical learning algorithms improves the efficiency for the detection of life threatening arrhythmias. PMID- 24239970 TI - Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1. AB - Glucocorticoids therapy is strongly limited since extended glucocorticoids can cause serious side effects, including increased susceptibility to develop the bone disease osteoporosis. Despite its side effects recognized importance to clinicians, seldom is known about how glucocorticoids directly impact bone forming osteoblasts. Previous studies showed that dexamethasone (DEX) induces excessive production of reactive oxygen species (ROS), and causes oxidative stress in rat hippocampal slice cultures. To assess the implications and investigate the mechanisms of glucocorticoid-elicited osteoporosis, we hypothesize that DEX exposure induces oxidative stress which leads to decreased Cbfa1 mRNA expression, and predict that the antioxidant N-acetylcysteine (NAC) mitigates the damaging effects of DEX. Oxidative stress is implicated in osteoporosis. Furthermore, the osteoblast transcriptional factor Cbfa1 is reported to play a protective role against osteoporosis in postmenopausal women. Cells treated with (0.1, 1, 10MUM) DEX exhibited signs of oxidative damages including depletion in total antioxidant capacity (T-AOC), increased ROS formation, and enhanced lipid peroxidation. Cbfa1 mRNA expression, by RT-PCR, was significantly reduced after exposure to (0.1, 1, 10MUM) DEX. Pretreatment with the antioxidant NAC (2mM) prevented DEX-induced decrease in Cbfa1 mRNA. This study provides insight into the underlying mechanisms of high dose DEX-induced osteotoxicity. DEX (0.1, 1, 10MUM) decreases the expression of Cbfa1 mRNA and inhibits differentiation and function of osteoblasts by inducing oxidative stress. The antioxidant NAC can mitigate the oxidative stress damaging effects of DEX. In addition, this study distinguishes itself by identifying Cbfa1 as a target for high dose DEX-induced osteotoxicity. PMID- 24239971 TI - Amplitude and phase-locking adaptation of neural oscillation in the rat auditory cortex in response to tone sequence. AB - Sensory adaptation allows stimulus sensitivity to be dynamically modulated according to stimulus statistics and plays pivotal roles in efficient neural computation. Here, it is hypothesized that in the auditory cortex, phase locking of local field potentials (LFPs) to test tones exhibits an adaptation property, i.e., phase-locking adaptation, which is distinct from the amplitude adaptation of oscillatory components. Series of alternating tone sequences were applied in which the inter-tone interval (ITI) and frequency difference (DeltaF) between successive tones were varied. Then, adaptation was characterized by the temporal evolution of the band-specific amplitude and phase locking evoked by the test tones. Differences as well as similarities were revealed between amplitude and phase-locking adaptations. First, both amplitude and phase-locking adaptations were enhanced by short ITIs and small DeltaFs. Second, the amplitude adaptation was more effective in a higher frequency band, while the phase-locking adaptation was more effective in a lower frequency band. Third, as with the adaptation of multiunit activities (MUAs), the amplitude adaptation occurred mainly within a second, while the phase-locking showed multi-second adaptation specifically in the gamma band for short ITI and small DeltaF conditions. Fourth, the amplitude adaptation and phase-locking adaptation were co-modulated in a within-second time scale, while this co-modulation was not observed in a multi-second time scale. These findings suggest that the amplitude and phase-locking adaptations have different mechanisms and functions. The phase-locking adaptation is likely to play more crucial roles in encoding a temporal structure of stimulus than the amplitude adaptation. PMID- 24239969 TI - Prediction and validation of apoptosis through cytochrome P450 activation by benzo[a]pyrene. AB - Polycyclic aromatic hydrocarbons (PAHs) processed by cytochrome P450 (CYP450) during metabolism is well reported to induce carcinogenesis. The present study has developed a new approach to examine apoptotic activity of a known PAH called benzo[a]pyrene (B[a]P), using protein-ligand and protein-protein interaction through in silico approach, followed by in vitro validation. In silico study showed that the conformational changes and energies involved in the binding of B[a]P to CYP1B1 was crucial with its target proteins. The data showed that activated B[a]P had high affinity to bind with aryl hydrocarbon receptor (AhR) with binding energy of -601.97kcal/mol. Interestingly, B[a]P-CYP1B1 complex showed strong binding affinity for caspase-8, -9, -3 with binding energy of 625.5, -479.3 and -514.2kcal/mol respectively. Moreover, the docking of specific caspase inhibitors in the complex showed weak interaction with low binding energy value as compared to B[a]P-CYP1B1 caspase complexes. To validate our in silico work, we showed B[a]P treated HaCaT cells triggered apoptosis with increase in caspase 8, caspase 9 and caspase 3/7 level. Further, in vitro work confirmed that B[a]P induced apoptosis was significantly suppressed in Ac-DEVD-CMK pre-treated cells. In addition, knockdown of CYP1B1 suppressed B[a]P induced apoptosis in HaCaT cells confirming a pivotal role of CYP1B1 in B[a]P induced apoptosis. Interestingly, through in silico modeling, we screened clotrimazole as a potent CYP1B1 inhibitor which completely inhibited B[a]P mediated activation. This hypothesis was validated by MTT assay, caspase activation measurement and showed remarkable inhibition of B[a]P induced cell death; thereby, highlighting a potent therapeutic role for industrial pollution associated diseases. PMID- 24239972 TI - The DNA replication, virogenesis and infection of canine minute virus in non permissive and permissive cells. AB - Canine minute virus (CnMV), a kind of autonomous parvovirus, is a member of genus bocavirus in parvovirdae family. In our previous study, we constructed and obtained infectious clones of CnMV, analyzed genome characteristics, RNA transcription profile, and revealed some molecular mechanisms of cytopathic effect of target cells. The purpose of this study was to investigate DNA replication, virogenesis and infectious tropism of CnMV in non-permissive and permissive cells. We demonstrated that the genomic DNA of CnMV, besides WRD cells, could replicate significantly in some non-permissive cells (CrFK, EBtR and COS-7) following transfection with infectious clone of CnMV, pI-MVC. Moreover, by using Western blotting and immunofluorescence, we found that the NS1 protein of CnMV was obviously expressed in both 293, CrFK, EBtR and COS-7 cells transfected with pI-MVC. Meanwhile, two-rounds of reinfection on WRD cells (blind passage) of the transfected cell lysates in CrFK, EBtR and COS-7 cells tranfected with pI-MVC showed that pI-MVC could produce infectious virions in these types of non permissive cells. Furthermore, it is confirmed that CnMV only infected WRD cells (permissive cells for CnMV), could not infect any non-permissive cells including CrFK, EBtR, COS-7, HK293, A549 and A9 cells. Taken together, for the first time, we have demonstrated that bocavirus CnMV DNA could replicate and form infectious progeny virus in some non-permissive cells. And what is more, unlike other parvoviruses, CnMV did not infect some non-permissive cells, although the DNA replication of CnMV occurred in these cells. PMID- 24239973 TI - Bluetongue virus in South America, Central America and the Caribbean. AB - Bluetongue virus (BTV) has been detected in many parts of the world but the data available from each continent are substantially different. Some regions are not covered by proper surveillance programs and thus, the real situation concerning the incidence of BTV in those regions is unknown. This is the case of Central America, South America and the Caribbean, where few outdated data about the presence and spread of BTV have been reported. In the present review, we update the BTV situation in those regions by compiling the serologic data available and analyzing the genetic information reported by the different research groups which are studying the disease in the region. PMID- 24239974 TI - Effect of high hydrostatic pressure on mycelial development, spore viability and enzyme activity of Penicillium Roqueforti. AB - This study investigated the effect of high hydrostatic pressure treatments on mycelial development, spore viability, and total proteolytic and lipolytic activity of Penicillium roqueforti PV-LYO 10 D. Fungus growing in liquid medium was pressure-treated at 300, 400, and 500 MPa for 10 min at 20 degrees C following seven days of incubation at 25 degrees C and analyzed periodically up to day 9 after treatments to evaluate the effect on fungal growth. Mycelial mass of P. roqueforti was significantly affected at all pressure treatments evaluated, being 15.48%, 22.28%, 30.03%, and 12.53% lower than controls on day 1, 3, 6, and 9 after 300 MPa treatment, respectively. In a similar way, at 400 and 500 MPa, mycelial mass was 31.08% and 60.34% lower than controls one day after treatments and 49.74% and 80.85% lower on day 9, respectively. The viability of P. roqueforti spores decreased by 36.53% at 300 MPa, and complete inactivation took place at >=400 MPa from an initial count of 7 log cfu/mL. Total proteolytic activity was not significantly affected at 300 MPa but was reduced by 18.22% at 400 MPa and by 43.18% at 500 MPa. Total lipolytic activity also decreased as the intensity of the pressure treatments increased. 21.69%, 39.12%, and 56.26% activity reductions were observed when treatments of 300, 400 and 500 MPa were applied, respectively. The results from this study show that pressure treatments are able to control growth, inactivate spores, and alter enzyme activity of P. roqueforti, which could be of interest in extending the shelf-life of blue-veined cheeses and other food products. PMID- 24239975 TI - Flow cytometry immunodetection and membrane integrity assessment of Escherichia coli O157:H7 in ready-to-eat pasta salad during refrigerated storage. AB - Over the past years, products of non-animal origin have been increasingly linked to foodborne diseases caused by the enterohemorrhagic pathogen Escherichia coli O157:H7. Contaminated fresh produce and derived ready-to-eat meals are of major concern, since no further or only minimal processing is applied. In this study, flow cytometry was evaluated as a rapid technique to detect E. coli O157:H7 by immunofluorescence, using polyclonal antibodies conjugated to R-phycoerythrin, in refrigerated ready-to-eat pasta salad containing acetic acid and benzoic acid. Signal filtering strategies were applied during sample analysis to reduce the limit of detection of the technique to 5 log CFU/g. Simultaneously with pathogen detection, physiological state was assessed by staining with the membrane integrity indicators propidium iodide and SYBR Green I. Fine tuning of dye concentrations and ratios allowed discrimination of not only cells with intact or damaged membranes, but also of cells with partially damaged membranes, which were considered injured cells. Then, changes in membrane integrity of inoculated E. coli O157:H7 cells were monitored throughout 14-day refrigerated storage. Most cells were injured at the beginning of refrigeration, but showed an intact membrane at the end. This suggests that injured E. coli O157:H7 cells underwent a membrane repair during exposure to refrigeration and acid stresses, and survived in ready-to-eat pasta salad. This highlights the importance of the implementation of control measures to limit the presence of this pathogen in non-animal origin food products. Additionally, the proposed immunodetection and membrane integrity three-color assay in food is a good tool to monitor the effect of a number of food-related treatments on E. coli O157:H7 cell membrane. PMID- 24239976 TI - Isolation and molecular characterization of Salmonella enterica, Escherichia coli O157:H7 and Shigella spp. from meat and dairy products in Egypt. AB - Foodborne pathogens are a major threat to food safety, especially in developing countries where hygiene and sanitation facilities are often poor. Salmonella enterica, Escherichia coli O157:H7 and Shigella spp. are among the major causes of outbreaks of foodborne diseases. This large-scale study investigated the prevalence of these foodborne pathogens in meat (beef and chicken) and dairy products collected from street vendors, butchers, retail markets and slaughterhouses in Egypt. A total of 1600 food samples (800 meat products and 800 dairy products) were analyzed using culture and PCR based methods. S. enterica, E. coli O157:H7 and Shigella spp. were detected in 69 (4.3%), 54 (3.4%) and 27 (1.7%) samples respectively. S. enterica serovar Typhimurium, S. enterica serovar Enteritidis, S. enterica serovar Infantis and non-typable serovars were detected in 28 (1.8%), 22 (1.4%), 16 (1.0%) and 3 (0.1%) samples respectively. All E. coli O157:H7 isolates were positive for stx1 and/or stx2 virulence toxin genes. Shigella flexneri, Shigella sonnei and Shigella dysenteriae were detected in 18 (1.2%), 7 (0.4%) and 2 (0.1%) samples respectively. The incidences of S. enterica and Shigella spp. were higher in meat products (53; 6.6% and 16; 2.0%, respectively) than in dairy products (16; 2.0% and 11; 1.4%, respectively), while, E. coli O157:H7 was higher in dairy products (29; 3.6%) than in meat products (25; 3.1%). The incidence of foodborne pathogens in meat and dairy products was determined in a large-scale survey in Africa. PMID- 24239977 TI - Heat-resistance of Hamigera avellanea and Thermoascus crustaceus isolated from pasteurized acid products. AB - Products containing sugar or fruit derivatives are usually subjected to a pasteurization process that can anyway be ineffective to kill ascospores from heat-resistant molds. Although the most occurring and economically relevant heat resistant species belong to Byssochlamys, Neosartorya, Talaromyces, and Eupenicillium genera, an increasing number of uncommon heat-resistant isolates have been recently detected as spoiling microorganisms in such products. Since Hamigera spp. and Thermoascus spp. were those more frequently isolated at SSICA, heat resistance of Hamigera avellanea and Thermoascus crustaceus strains from pasteurized acid products was studied in apple juice, in blueberry and grape juice and in a buffered glucose solution. Data obtained from thermal death curves and statistical elaboration of raw data showed that D values of H. avellanea may vary between 11.11 and 66.67 min at 87 degrees C, between 4.67 and 13.51 at 90 degrees C, and between 0.43 and 1.52 min at 95 degrees C. Similarly, D values of T. crustaceus may vary between 18.52 and 90.91 min at 90 degrees C, between 2.79 and 19.23 at 93 degrees C, and between 1.11 and 2.53 min at 95 degrees C. For both strains studied, the z-values calculated from the decimal reduction time curves did not prove to be significantly influenced by the heating medium, that being 4.35 degrees C, 5.39 degrees C or 5.27 degrees C for H. avellanea and 4.42 degrees C, 3.69 degrees C or 3.37 degrees C for T. crustaceus, respectively in apple juice, in blueberry and grape juice or in the buffered glucose solution. Considering the pasteurization treatments industrially applied to fruit-based foods, the variation of thermal parameters does not seem to be a possible way to avoid product spoilage by these two species and only good practices applied to reduce the original load of heat-resistant fungi can help producers to prevent losses in contaminated finished products, as usually happens for other heat resistant molds. PMID- 24239978 TI - Isolation and characterization of faecal bifidobacteria and lactobacilli isolated from dogs and primates. AB - Although bifidobacteria and lactobacilli have been suggested beneficial for the host and are components of many probiotics and competitive exclusion mixtures, the knowledge on abundance, metabolic and probiotic characteristics in isolates from dogs and monkeys is still limited. The present study was aimed to isolate Bifidobacterium and Lactobacillus strains (faeces of 22 dogs and of 5 primates: Cebus apella, Eulemur fulvus, Erythrocebus patas, Macaca fascicularis, Papio hamadryas) with the MALDI-TOF identification system Lactobacillus murinus, Bifidobacterium animalis and Pediococcus acidilactici were more frequently isolated species in dogs while Lactobacillus plantarum was isolated in several species of primates. Ten strains of 6 species were assayed for enzymatic activities (only Lactobacillus reuteri strains showed no undesirable enzymatic activity), antimicrobial susceptibility (detected higher minimum inhibitory concentration levels for tetracycline and gentamicin), and inhibitory activity against 15 indicator bacteria. All strains inhibited Gram-negative indicators while lactobacilli showed larger inhibition zones than bifidobacteria. L. reuteri II/3b/a (isolate from M. fascicularis) showed the best antimicrobial properties. Resistance to bile (0.3% w/v) was observed in all tested strains (no decrease of CFU/ml) whereas the decrease of 68.4-94.4% (after 90 min exposition) and 78.4 99.9% CFU/ml (after 180 min) depending on the strain was detected in the artificial gastric juice. PMID- 24239979 TI - In vitro fermentation of prebiotic oligosaccharides by Bifidobacterium lactis HN019 and Lactobacillus spp. AB - The utilisation of various prebiotic oligosaccharides by probiotic strains of Bifidobacterium lactis, Lactobacillus rhamnosus and Lactobacillus acidophilus was investigated in order to determine the synbiotic potential of various prebiotic/probiotic combinations. Analysis by HPLC and high-performance anion exchange chromatography of the cell-free medium taken during growth of the three probiotic bacteria showed differences in the consumption of the various oligosaccharides. Analysis of galactooligosaccharides showed that both L. rhamnosus and B. lactis consumed mostly mono- and di-saccharide, while L. acidophilus consumed oligosaccharides up to trisaccharide. Both B. lactis and L. acidophilus utilised fructooligosaccharides and inulin, but showed different patterns of oligosaccharide consumption. Only L. rhamnosus grew on beta-glucan oligosaccharides and preferentially consumed the trisaccharide. The results indicate the synbiotic potential of the various probiotic/prebiotic combinations, particularly L. acidophilus/galactooligosaccharides, L. acidophilus/fructooligosaccharides or inulin and L. rhamnosus/beta-glucan oligosaccharides. PMID- 24239980 TI - Positive effect of reduced aeration rate on secretion of alpha-amylase and neutral proteases during pressurised fermentation of thermophilic Bacillus caldolyticus. AB - The thermophilic microorganism Bacillus caldolyticus was incubated in laboratory scale stirred bioreactors under pressurised conditions at different aeration rates. Increased amounts of CO2/bicarbonate were solubilised under the chosen conditions. A reduction in aeration rate from 1 vvm to 0.1 vvm resulted in accumulation of CO2 and bicarbonate up to 126 mg l(-1) and 733 mg l(-1), respectively and also increased secretion of alpha-amylase and neutral proteases (increases of 123% and 52%, respectively). In this paper, the effect of reduced aeration rate on CO2/bicarbonate concentration and enzyme activities is presented. The selected fermentation conditions are closely related to those prevalent in large scale bioreactors and may offer the possibility of achieving high enzyme yields at reduced aeration costs on an industrial scale. PMID- 24239981 TI - Expression and methylation status of female-predominant GH-dependent liver genes are modified by neonatal androgenization in female mice. AB - Neonatal androgenization masculinizes the GH axis and thus may impact on liver gene regulation. Neonatal testosterone administration to female mice decreased (defeminized) female predominant GH-dependent liver gene expression (Hnf6, Adh1, Prlr, Cyp3a41) and did not modify male predominant genes (Cyp7b1, Cyp4a12, Slp). Female predominance of Cis mRNA, an inhibitor of episodic GH signaling pathway, was unaltered. At birth, Cyp7b1 promoter exhibited a higher methylation status in female livers, while the Hnf6 promoter was equally methylated in both sexes; no differences in gene expression were detected at this age. In adulthood, consistent with sex specific predominance, lower methylation status was determined for the Cyp7b1 promoter in males, and for the Hnf6 promoter in females, and this last difference was prevented by neonatal androgenization. Therefore, early steroid treatment or eventually endocrine disruptor exposure may alter methylation status and sexual dimorphic expression of liver genes, and consequently modify liver physiology in females. PMID- 24239982 TI - Evidence for an internal and functional circadian clock in rat pituitary cells. AB - In primary cultures of rat pituitary cells and in a pituitary sommatolactotroph cell line (GH4C1), endogenous core-clock- as well as hormone-genes such as prolactin displayed a rhythmic expression pattern, fitted by a sinusoidal equation in which the period value was close to the circadian one. This is consistent with the presence of a functional circadian oscillator in pituitary cells whose importance was ascertained in GH4C1 cell lines stably expressing a dominant negative mutant of BMAL1. In these cells, both endogenous core-clock- and prolactin-genes no more displayed a circadian pattern. Some genes we recently identified as mouse pituitary BMAL1-regulated genes in a DNA-microarray study, lost their circadian pattern in these cells, suggesting that BMAL1 controlled these genes locally in the pituitary. The intra-pituitary circadian oscillator could then play a role in the physiology of the gland that would not be seen anymore as a structure only driven by hypothalamic rhythmic control. PMID- 24239984 TI - Heliox for mechanically ventilated newborns with bronchopulmonary dysplasia. AB - OBJECTIVE: We assessed the safety and studied the influence of short-term helium oxygen (heliox) mechanical ventilation (MV) on respiratory function, gas exchange and oxygenation in infants with bronchopulmonary dysplasia (BPD) or at high risk for BPD. DESIGN: A pilot, time-series study. SETTING: Neonatal intensive care unit. PATIENTS: Infants with severe BPD who required MV. INTERVENTIONS: MV with helium-oxygen and air-oxygen mixtures. MAIN OUTCOME MEASURES: Respiratory parameters, acid-base balance, oxygenation and vital signs were recorded at five time points: initially during MV with air-oxygen, after 15 and 60 min of helium oxygen MV, and 15 and 60 min after return to air-oxygen MV. RESULTS: 15 infants with BPD were enrolled. Helium-oxygen MV was well tolerated and was associated with a statistically significant increase in tidal volume, dynamic compliance and peak expiratory flow rate. An improvement in oxygenation and a decrease in fraction of inspired oxygen was also observed. During helium-oxygen MV there was a significant decrease in the oxygenation index and alveolar-arterial oxygen tension difference. The PaO2/fraction of inspired oxygen (FiO2) ratio increased significantly during helium-oxygen ventilation. A decrease in PaCO2 and an increase in pH were also observed during helium-oxygen administration, however this was not statistically significant. After ventilation with helium-oxygen was discontinued, the infants' respiratory function and oxygenation deteriorated and supplemental oxygen requirements increased accordingly. CONCLUSIONS: Helium oxygen MV is safe and resulted in improvement of respiratory function and oxygenation in infants with severe BPD requiring MV. PMID- 24239983 TI - Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone. AB - Prior studies have linked renoprotective effects of estrogens to G-protein coupled estrogen receptor-1 (GPER-1) and suggest that aldosterone may also activate GPER-1. Here, the role of GPER-1 in murine renal tissue was further evaluated by examining its anatomical distribution, subcellular distribution and steroid binding specificity. Dual immunofluorescent staining using position specific markers showed that GPER-1 immunoreactivity primarily resides in distal convoluted tubules and the Loop of Henle (stained with Tamm-Horsfall Protein-1). Lower GPER-1 expression was observed in proximal convoluted tubules marked with megalin, and GPER-1 was not detected in collecting ducts. Plasma membrane fractions prepared from whole kidney tissue or HEK293 cells expressing recombinant human GPER-1 (HEK-GPER-1) displayed high-affinity, specific [(3)H] 17beta-estradiol ([(3)H]-E2) binding, but no specific [(3)H]-aldosterone binding. In contrast, cytosolic preparations exhibited specific binding to [(3)H] aldosterone but not to [(3)H]-E2, consistent with the subcellular distribution of GPER-1 and mineralocorticoid receptor (MR) in these preparations. Aldosterone and MR antagonists, spironolactone and eplerenone, failed to compete for specific [(3)H]-E2 binding to membranes of HEK-GPER-1 cells. Furthermore, aldosterone did not increase [(35)S]-GTP-gammaS binding to membranes of HEK-GPER-1 cells, indicating that it is not involved in G protein signaling mediated through GPER 1. During the secretory phases of the estrus cycle, GPER-1 is upregulated on cortical epithelia and localized to the basolateral surface during proestrus and redistributed intracellularly during estrus. GPER-1 is down-modulated during luteal phases of the estrus cycle with significantly less receptor on the surface of renal epithelia. Our results demonstrate that GPER-1 is associated with specific estrogen binding and not aldosterone binding and that GPER-1 expression is modulated during the estrus cycle which may suggest a physiological role for GPER-1 in the kidney during reproduction. PMID- 24239985 TI - Gene expression profile based classification models of psoriasis. AB - Psoriasis is an autoimmune disease, which symptoms can significantly impair the patient's life quality. It is mainly diagnosed through the visual inspection of the lesion skin by experienced dermatologists. Currently no cure for psoriasis is available due to limited knowledge about its pathogenesis and development mechanisms. Previous studies have profiled hundreds of differentially expressed genes related to psoriasis, however with no robust psoriasis prediction model available. This study integrated the knowledge of three feature selection algorithms that revealed 21 features belonging to 18 genes as candidate markers. The final psoriasis classification model was established using the novel Incremental Feature Selection algorithm that utilizes only 3 features from 2 unique genes, IGFL1 and C10orf99. This model has demonstrated highly stable prediction accuracy (averaged at 99.81%) over three independent validation strategies. The two marker genes, IGFL1 and C10orf99, were revealed as the upstream components of growth signal transduction pathway of psoriatic pathogenesis. PMID- 24239986 TI - Correcting and combining time series forecasters. AB - Combined forecasters have been in the vanguard of stochastic time series modeling. In this way it has been usual to suppose that each single model generates a residual or prediction error like a white noise. However, mostly because of disturbances not captured by each model, it is yet possible that such supposition is violated. The present paper introduces a two-step method for correcting and combining forecasting models. Firstly, the stochastic process underlying the bias of each predictive model is built according to a recursive ARIMA algorithm in order to achieve a white noise behavior. At each iteration of the algorithm the best ARIMA adjustment is determined according to a given information criterion (e.g. Akaike). Then, in the light of the corrected predictions, it is considered a maximum likelihood combined estimator. Applications involving single ARIMA and artificial neural networks models for Dow Jones Industrial Average Index, S&P500 Index, Google Stock Value, and Nasdaq Index series illustrate the usefulness of the proposed framework. PMID- 24239987 TI - Hybrid fault diagnosis of nonlinear systems using neural parameter estimators. AB - This paper presents a novel integrated hybrid approach for fault diagnosis (FD) of nonlinear systems taking advantage of both the system's mathematical model and the adaptive nonlinear approximation capability of computational intelligence techniques. Unlike most FD techniques, the proposed solution simultaneously accomplishes fault detection, isolation, and identification (FDII) within a unified diagnostic module. At the core of this solution is a bank of adaptive neural parameter estimators (NPEs) associated with a set of single-parameter fault models. The NPEs continuously estimate unknown fault parameters (FPs) that are indicators of faults in the system. Two NPE structures, series-parallel and parallel, are developed with their exclusive set of desirable attributes. The parallel scheme is extremely robust to measurement noise and possesses a simpler, yet more solid, fault isolation logic. In contrast, the series-parallel scheme displays short FD delays and is robust to closed-loop system transients due to changes in control commands. Finally, a fault tolerant observer (FTO) is designed to extend the capability of the two NPEs that originally assumes full state measurements for systems that have only partial state measurements. The proposed FTO is a neural state estimator that can estimate unmeasured states even in the presence of faults. The estimated and the measured states then comprise the inputs to the two proposed FDII schemes. Simulation results for FDII of reaction wheels of a three-axis stabilized satellite in the presence of disturbances and noise demonstrate the effectiveness of the proposed FDII solutions under partial state measurements. PMID- 24239988 TI - Simulations of breast cancer imaging using gamma-ray stimulated emission computed tomography. AB - Here, we present an innovative imaging technology for breast cancer using gamma ray stimulated spectroscopy based on the nuclear resonance fluorescence (NRF) technique. In NRF, a nucleus of a given isotope selectively absorbs gamma rays with energy exactly equal to one of its quantized energy states, emitting an outgoing gamma ray with energy nearly identical to that of the incident gamma ray. Due to its application of NRF, gamma-ray stimulated spectroscopy is sensitive to trace element concentration changes, which are suspected to occur at early stages of breast cancer, and therefore can be potentially used to noninvasively detect and diagnose cancer in its early stages. Using Monte-Carlo simulations, we have designed and demonstrated an imaging system that uses gamma ray stimulated spectroscopy for visualizing breast cancer. We show that gamma-ray stimulated spectroscopy is able to visualize breast cancer lesions based primarily on the differences in the concentrations of trace elements between diseased and healthy tissue, rather than differences in density that are crucial for X-ray mammography. The technique shows potential for early breast cancer detection; however, improvements are needed in gamma-ray laser technology for the technique to become a clinically feasible method of detecting and diagnosing cancer at early stages. PMID- 24239989 TI - A novel skeleton based quantification and 3-D volumetric visualization of left atrium fibrosis using late gadolinium enhancement magnetic resonance imaging. AB - This work presents the results of a new tool for 3-D segmentation, quantification and visualization of cardiac left atrium fibrosis, based on late gadolinium enhancement magnetic resonance imaging (LGE-MRI), for stratifying patients with atrial fibrillation (AF) that are candidates for radio-frequency catheter ablation. In this study 10 consecutive patients suffering AF with different grades of atrial fibrosis were considered. LGE-MRI and magnetic resonance angiography (MRA) images were used to detect and quantify fibrosis of the left atrium using a threshold and 2-D skeleton based approach. Quantification and 3-D volumetric views of atrial fibrosis were compared with quantification and 3-D bipolar voltage maps measured with an electro-anatomical mapping (EAM) system, the clinical reference standard technique for atrial substrate characterization. Segmentation and quantification of fibrosis areas proved to be clinically reliable among all different fibrosis stages. The proposed tool obtains discrepancies in fibrosis quantification less than 4% from EAM results and yields accurate 3-D volumetric views of fibrosis of left atrium. The novel 3-D visualization and quantification tool based on LGE-MRI allows detection of cardiac left atrium fibrosis areas. This noninvasive method provides a clinical alternative to EAM systems for quantification and localization of atrial fibrosis. PMID- 24239990 TI - Lung segmentation in chest radiographs using anatomical atlases with nonrigid registration. AB - The National Library of Medicine (NLM) is developing a digital chest X-ray (CXR) screening system for deployment in resource constrained communities and developing countries worldwide with a focus on early detection of tuberculosis. A critical component in the computer-aided diagnosis of digital CXRs is the automatic detection of the lung regions. In this paper, we present a nonrigid registration-driven robust lung segmentation method using image retrieval-based patient specific adaptive lung models that detects lung boundaries, surpassing state-of-the-art performance. The method consists of three main stages: 1) a content-based image retrieval approach for identifying training images (with masks) most similar to the patient CXR using a partial Radon transform and Bhattacharyya shape similarity measure, 2) creating the initial patient-specific anatomical model of lung shape using SIFT-flow for deformable registration of training masks to the patient CXR, and 3) extracting refined lung boundaries using a graph cuts optimization approach with a customized energy function. Our average accuracy of 95.4% on the public JSRT database is the highest among published results. A similar degree of accuracy of 94.1% and 91.7% on two new CXR datasets from Montgomery County, MD, USA, and India, respectively, demonstrates the robustness of our lung segmentation approach. PMID- 24239991 TI - Model based inversion for deriving maps of histological parameters characteristic of cancer from ex-vivo multispectral images of the colon. AB - A model-based inversion method was used to obtain quantitative estimates of histological parameters from multispectral images of the colon and to examine their potential for discriminating between normal and pathological tissues. Pixel wise estimates of the mucosal blood volume fraction, density of the scattering particles and thickness were derived using a two-stage method. In the first (forward) stage reflectance spectra corresponding to given instances of the parameter values were computed using Monte Carlo simulation of photon propagation through a multi-layered tissue. In the second (inversion) stage the parameter values were obtained via optimization using an iterated conditional modes algorithm based on Discrete Markov Random Fields. The method was validated on computer generated data contaminated with noise giving a mean normalized root mean square deviation (NRMSD) of 2.04. Validation on ex vivo images demonstrated that parametric maps show gross correspondence with histological features of mucosa characteristic of cancerous, precancerous and noncancerous colon lesions. The key signs of abnormality were shown to be the increase in the blood volume fraction and decrease in the density of scattering particles. PMID- 24239992 TI - Suffering in silence: a qualitative study of second victims of adverse events. AB - INTRODUCTION: The term 'second victim' refers to the healthcare professional who experiences emotional distress following an adverse event. This distress has been shown to be similar to that of the patient-the 'first victim'. The aim of this study was to investigate how healthcare professionals are affected by their involvement in adverse events with emphasis on the organisational support they need and how well the organisation meets those needs. METHODS: 21 healthcare professionals at a Swedish university hospital who each had experienced an adverse event were interviewed. Data from semi-structured interviews were analysed by qualitative content analysis using QSR NVivo software for coding and categorisation. RESULTS: Our findings confirm earlier studies showing that emotional distress, often long-lasting, follows from adverse events. In addition, we report that the impact on the healthcare professional was related to the organisation's response to the event. Most informants lacked organisational support or they received support that was unstructured and unsystematic. Further, the formal investigation seldom provided adequate and timely feedback to those involved. The insufficient support and lack of feedback made it more difficult to emotionally process the event and reach closure. DISCUSSION: This article addresses the gap between the second victim's need for organisational support and the organisational support provided. It also highlights the need for more transparency in the investigation of adverse events. Future research should address how advanced support structures can meet these needs and provide learning opportunities for the organisation. These issues are central for all hospital managers and policy makers who wish to prevent and manage adverse events and to promote a positive safety culture. PMID- 24239994 TI - Diphenyl diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats. AB - Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect. PMID- 24239993 TI - Musk shrews selectively bred for motion sickness display increased anesthesia induced vomiting. AB - Susceptibility to motion sickness is a predictor of postoperative nausea and vomiting, and studies in humans suggest that genetic factors determine sensitivity to motion sickness. The aim of the current study was to determine if a preclinical model could be selectively bred for motion-induced emesis and to assess a potential relationship to anesthesia-induced emesis. Musk shrews were tested for motion-induced emesis using a shaker plate (10min, 1Hz, and 4cm of lateral displacement). Animals were rank ordered for motion-induced emesis and selectively bred to produce high and low response strains. Shrews were also tested with nicotine (5mg/kg, sc), copper sulfate (CuSO4; 120mg/kg, ig), and isoflurane anesthesia (10min; 3%) to measure responses to a panel of emetic stimuli. High response strain shrews demonstrated significantly more emetic episodes to motion exposure compared to low response strain animals in the F1 and F2 generations. In F2 animals, there were no significant differences in total emetic responses or emetic latency between strains after nicotine injection or CuSO4 gavage. However, isoflurane exposure stimulated more emesis in F1 and F2 high versus low strain animals, which suggests a relationship between vestibular- and inhalational anesthesia-induced emesis. Overall, these results indicate genetic determinants of motion sickness in a preclinical model and a potential common mechanism for motion sickness and inhalational anesthesia-induced emesis. Future work may include genetic mapping of potential "emetic sensitivity genes" to develop novel therapies or diagnostics for patients with high risk of nausea and vomiting. PMID- 24239995 TI - Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue. AB - Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer's solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives. PMID- 24239996 TI - Cinnarizine food-effects in beagle dogs can be avoided by administration in a Self Nano Emulsifying Drug Delivery System (SNEDDS). AB - PURPOSE: To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. METHOD: A conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n=5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy(r)). The food-effect was evaluated by comparing Tmax, Cmax and Bioavailability (F) for the different formulations. RESULTS: Food effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5times and bioavailability increased in fed state (from 20.9+/-5.7 to 53.8+/-30.1). Apart from an extended Tmax (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted=58.1+/-16.7, vs. 32.7+/-11.5), (Ffed=79.3+/ 14.7 vs. 43.7+/-6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. CONCLUSION: Food effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations. PMID- 24239997 TI - A MAP-based image interpolation method via Viterbi decoding of Markov chains of interpolation functions. AB - A new method of image resolution up-conversion (image interpolation) based on maximum a posteriori sequence estimation is proposed. Instead of making a hard decision about the value of each missing pixel, we estimate the missing pixels in groups. At each missing pixel of the high resolution (HR) image, we consider an ensemble of candidate interpolation methods (interpolation functions). The interpolation functions are interpreted as states of a Markov model. In other words, the proposed method undergoes state transitions from one missing pixel position to the next. Accordingly, the interpolation problem is translated to the problem of estimating the optimal sequence of interpolation functions corresponding to the sequence of missing HR pixel positions. We derive a parameter-free probabilistic model for this to-be-estimated sequence of interpolation functions. Then, we solve the estimation problem using a trellis representation and the Viterbi algorithm. Using directional interpolation functions and sequence estimation techniques, we classify the new algorithm as an adaptive directional interpolation using soft-decision estimation techniques. Experimental results show that the proposed algorithm yields images with higher or comparable peak signal-to-noise ratios compared with some benchmark interpolation methods in the literature while being efficient in terms of implementation and complexity considerations. PMID- 24239998 TI - 3D visual activity assessment based on natural scene statistics. AB - One of the most challenging ongoing issues in the field of 3D visual research is how to perceptually quantify object and surface visualizations that are displayed within a virtual 3D space between a human eye and 3D display. To seek an effective method of quantification, it is necessary to measure various elements related to the perception of 3D objects at different depths. We propose a new framework for quantifying 3D visual information that we call 3D visual activity (3DVA), which utilizes natural scene statistics measured over 3D visual coordinates. We account for important aspects of 3D perception by carrying out a 3D coordinate transform reflecting the nonuniform sampling resolution of the eye and the process of stereoscopic fusion. The 3DVA utilizes the empirical distortions of wavelet coefficients to a parametric generalized Gaussian probability distribution model and a set of 3D perceptual weights. We conducted a series of simulations that demonstrate the effectiveness of the 3DVA for quantifying the statistical dynamics of visual 3D space with respect to disparity, motion, texture, and color. A successful example application is also provided, whereby 3DVA is applied to the problem of predicting visual fatigue experienced when viewing 3D displays. PMID- 24239999 TI - Learning Category-Specific Dictionary and Shared Dictionary for Fine-Grained Image Categorization. AB - This paper targets fine-grained image categorization by learning a category specific dictionary for each category and a shared dictionary for all the categories. Such category-specific dictionaries encode subtle visual differences among different categories, while the shared dictionary encodes common visual patterns among all the categories. To this end, we impose incoherence constraints among the different dictionaries in the objective of feature coding. In addition, to make the learnt dictionary stable, we also impose the constraint that each dictionary should be self-incoherent. Our proposed dictionary learning formulation not only applies to fine-grained classification, but also improves conventional basic-level object categorization and other tasks such as event recognition. Experimental results on five data sets show that our method can outperform the state-of-the-art fine-grained image categorization frameworks as well as sparse coding based dictionary learning frameworks. All these results demonstrate the effectiveness of our method. PMID- 24240000 TI - A rain pixel recovery algorithm for videos with highly dynamic scenes. AB - Rain removal is a very useful and important technique in applications such as security surveillance and movie editing. Several rain removal algorithms have been proposed these years, where photometric, chromatic, and probabilistic properties of the rain have been exploited to detect and remove the rainy effect. Current methods generally work well with light rain and relatively static scenes, when dealing with heavier rainfall in dynamic scenes, these methods give very poor visual results. The proposed algorithm is based on motion segmentation of dynamic scene. After applying photometric and chromatic constraints for rain detection, rain removal filters are applied on pixels such that their dynamic property as well as motion occlusion clue are considered; both spatial and temporal informations are then adaptively exploited during rain pixel recovery. Results show that the proposed algorithm has a much better performance for rainy scenes with large motion than existing algorithms. PMID- 24240001 TI - Camera model identification based on the heteroscedastic noise model. AB - The goal of this paper is to design a statistical test for the camera model identification problem. The approach is based on the heteroscedastic noise model, which more accurately describes a natural raw image. This model is characterized by only two parameters, which are considered as unique fingerprint to identify camera models. The camera model identification problem is cast in the framework of hypothesis testing theory. In an ideal context where all model parameters are perfectly known, the likelihood ratio test (LRT) is presented and its performances are theoretically established. For a practical use, two generalized LRTs are designed to deal with unknown model parameters so that they can meet a prescribed false alarm probability while ensuring a high detection performance. Numerical results on simulated images and real natural raw images highlight the relevance of the proposed approach. PMID- 24240002 TI - How to select good neighboring images in depth-map merging based 3D modeling. AB - Depth-map merging based 3D modeling is an effective approach for reconstructing large-scale scenes from multiple images. In addition to generate high quality depth maps at each image, how to select suitable neighboring images for each image is also an important step in the reconstruction pipeline, unfortunately to which little attention has been paid in the literature until now. This paper is intended to tackle this issue for large scale scene reconstruction where many unordered images are captured and used with substantial varying scale and view angle changes. We formulate the neighboring image selection as a combinatorial optimization problem and use the quantum-inspired evolutionary algorithm to seek its optimal solution. Experimental results on the ground truth data set show that our approach can significantly improve the quality of the depth-maps as well as final 3D reconstruction results with high computational efficiency. PMID- 24240003 TI - Novel speed-up strategies for non-local means denoising with patch and edge patch based dictionaries. AB - In this paper, a novel technique to speed-up a nonlocal means (NLM) filter is proposed. In the original NLM filter, most of its computational time is spent on finding distances for all the patches in the search window. Here, we build a dictionary in which patches with similar photometric structures are clustered together. Dictionary is built only once with high resolution images belonging to different scenes. Since the dictionary is well organized in terms of indexing its entries, it is used to search similar patches very quickly for efficient NLM denoising. We achieve a substantial reduction in computational cost compared with the original NLM method, especially when the search window of NLM is large, without much affecting the PSNR. Second, we show that by building a dictionary for edge patches as opposed to intensity patches, it is possible to reduce the dictionary size; thus, further improving the computational speed and memory requirement. The proposed method preclassifies similar patches with the same distance measure as used by NLM method. The proposed algorithm is shown to outperform other prefiltering based fast NLM algorithms computationally as well as qualitatively. PMID- 24240004 TI - Large extracellular spikes recordable from axons in microtunnels. AB - When extracellular action potentials (spikes) from cultured neurons are recorded using microelectrode arrays in open wells, their amplitudes are usually quite small (often below the noise level) despite the extracellular currents originating from the relatively large surface area of neural cell somata. In this paper rat cortical neurons were seeded into one well of a two well system separated by 3 * 10 MUm microtunnels and then seven days later into the second well forming a feed-forward network between two small neuronal assemblies. In contrast to measurements in the open well spikes recorded from axons within the restricted volumes imposed by the microtunnels are often several orders of magnitude larger than in the open well, with high signal to noise ratio, despite the currents originating in the much smaller surface area of the axon. Average signal amplitudes exceeding 250 MUV are typical, with some signals as large as 4.5 mV (signal-to-noise ratio up to 450), 20 times greater than the maximum recorded from electrodes in adjacent but open wells. We confirm the dependence of signal amplitude on the impedance of the microtunnel and discuss possible reasons for the phenomenon. PMID- 24240005 TI - Sorting and tracking neuronal spikes via simple thresholding. AB - A fundamental goal in systems neuroscience is to assess the individual as well as the synergistic roles of single neurons in a recorded ensemble as they relate to an observed behavior. A mandatory step to achieve this goal is to sort spikes in an extracellularly recorded mixture that belong to individual neurons through feature extraction and clustering techniques. Here, we propose an approach for approximating the often nonlinear and time varying decision boundaries between spike-derived feature classes based on a simple, yet optimal thresholding mechanism. Because thresholding is a binary classifier, we show that the complex nonlinear decision boundaries required for spike class discrimination can be achieved by adequately fusing a set of weak binary classifiers. The thresholds for these binary classifiers are adaptively estimated through a learning algorithm that maximizes the separability between the sparsely represented classes. Based on our previous work, the approach substantially reduces the computational complexity of extracting, aligning and sorting multiple single unit activity early in the data stream. Here, we also show its ability to track changes in spike features over extended periods of time, making it highly suitable for basic neuroscience studies as well as for implementation in miniaturized, fully implantable electronics in brain-machine interface applications. PMID- 24240006 TI - Complexity analysis of EMG signals for patients after stroke during robot-aided rehabilitation training using fuzzy approximate entropy. AB - The paper presents a novel viewpoint to monitor the motor function improvement during a robot-aided rehabilitation training. Eight chronic poststroke subjects were recruited to attend the 20-session training, and in each session, subjects were asked to perform voluntary movements of elbow flexion and extension together with the robotic system. The robotic system was continuously controlled by the electromyographic (EMG) signal from the affected triceps. Fuzzy approximate entropy (fApEn) was applied to investigate the complexity of the EMG segment, and maximum voluntary contraction (MVC) during elbow flexion and extension was applied to reflect force generating capacity of the affected muscles. The results showed that the group mean fApEn of EMG signals from triceps and biceps increased significantly after the robot-aided rehabilitation training . There was also significant increase in maximum voluntary flexion and extension torques after the robot-aided rehabilitation training . There was significant correlation between fApEn of agonist and MVC , which implied that the increase of motorneuron number is one of factors that may explain the increase in muscle strength. These findings based on fApEn of the EMG signals expand the existing interpretation of training-induced function improvement in patients after stroke, and help us to understand the neurological change induced by the robot-aided rehabilitation training. PMID- 24240007 TI - A DSP for sensing the bladder volume through afferent neural pathways. AB - In this paper, we present a digital signal processor (DSP) capable of monitoring the urinary bladder volume through afferent neural pathways. The DSP carries out real-time detection and can discriminate extracellular action potentials, also known as on-the-fly spike sorting. Next, the DSP performs a decoding method to estimate either three qualitative levels of fullness or the bladder volume value, depending on the selected output mode. The proposed DSP was tested using both realistic synthetic signals with a known ground-truth, and real signals from bladder afferent nerves recorded during acute experiments with animal models. The spike sorting processing circuit yielded an average accuracy of 92% using signals with highly correlated spike waveforms and low signal-to-noise ratios. The volume estimation circuits, tested with real signals, reproduced accuracies achieved by offline simulations in Matlab, i.e., 94% and 97% for quantitative and qualitative estimations, respectively. To assess feasibility, the DSP was deployed in the Actel FPGA Igloo AGL1000V2, which showed a power consumption of 0.5 mW and a latency of 2.1 ms at a 333 kHz core frequency. These performance results demonstrate that an implantable bladder sensor that perform the detection, discrimination and decoding of afferent neural activity is feasible. PMID- 24240008 TI - A low power sub- MUW chemical gilbert cell for ISFET differential reaction monitoring. AB - This paper presents a low power current-mode method for monitoring differentially derived changes in pH from ion-sensitive field-effect transistor (ISFET) sensors, by adopting the Chemical Gilbert Cell. The fabricated system, with only a few transistors, achieves differential measurements and therefore drift minimisation of continuously recorded pH signals obtained from biochemical reactions such as DNA amplification in addition to combined gain tunability using only a single current. Experimental results are presented, demonstrating the capabilities of the front-end at a microscopic level through integration in a lab-on-chip (LoC) setup combining a microfluidic assembly, suitable for applications that require differential monitoring in small volumes, such as DNA detection where more than one gene needs to be studied. The system was designed and fabricated in a typical 0.35 MU m CMOS process with the resulting topology achieving good differential pH sensitivity with a measured low power consumption of only 165 nW due to weak inversion operation. A tunable gain is demonstrated with results confirming 15.56 dB gain at 20 nA of ISFET bias current and drift reduction of up to 100 times compared to a single-ended measurement is also reported due to the differential current output, making it ideal for robust, low-power chemical measurement. PMID- 24240009 TI - Retinal nerve fiber layer thickness profiles associated with ocular laterality and dominance. AB - Although human anatomy is arranged symmetrically based on a central vertical axis, the majority of persons will use one side of their body more readily than the other. Interestingly, these lateral body dominances including ocular dominance are all rightward. The asymmetry in retinal nerve fiber layer (RNFL) thickness between the right and left eyes in healthy subjects has been reported in several studies, and the reason for this structural difference between right and left eyes is unclear. In the manuscript, we hypothesized that the characteristics of ocular dominance are reflected in the RNFL profile and may be related to inter-ocular structural differences between right and left eyes. In this study, ocular dominance occurred mostly in right eyes (right vs. left: 78.77% vs. 21.22%; P<0.001). According to ocular dominance and laterality, different relationships between the inferior and superior RNFLs were observed. The right eyes had a thicker RNFL, except in the superior quadrant, than the left eyes. Regardless of laterality, inferior RNFL was thicker than superior RNFL in the dominant eyes. To our knowledge, this paper is the first report demonstrating the RNFL characteristics associated with ocular dominance. PMID- 24240010 TI - Dynamic aspects of cerebral hypoxic preconditioning measured in an in vitro model. AB - Preconditioning increases the neurons' resistance to subsequent hypoxia. An in vitro study was conducted to explore kinetic aspects of hypoxic preconditioning. Hippocampal slices were exposed to one single or repeated episodes of oxygen and glucose deprivation (OGD). The interval between OGD episodes varied between 30 min and 180 min. OGD led to a significant reduction in the population spike amplitude. Subsequent episodes of OGD did not result in a further reduction in the population spike amplitude if the interval between the episodes was ca. 60 min, which demonstrated that there were preconditioning effects. In the experiment using an interval of 30 min, population spike amplitude decreased after each OGD episode. The set-up described is useful for detecting damaging effects of OGD as well as preconditioning effects. A time window of ca. 60 min is required to induce protective mechanisms. PMID- 24240011 TI - Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice. AB - The GPR30, a former orphan GPCR, is a putative membrane estrogen receptor that can activate rapid signaling pathways such as extracellular regulated kinase (ERK) in a variety of cells and may contribute to estrogen's effects in the central nervous system. The distribution of GPR30 in the limbic system predicts a role for this receptor in the regulation of learning and memory and anxiety by estrogens. Though acute G-1 treatment is reported to be anxiogenic in ovariectomised female mice and in gonadally intact male mice, the effect of GPR30 activation is unknown in gonadectomised male mice. In this study, we show that an acute administration of G-1 to gonadectomised male mice, but not female mice, was anxiolytic on an elevated plus maze task, without affecting locomotor activity. In addition, though G-1 treatment did not regulate ERK, it was associated with increased estrogen receptor (ER)alpha phosphorylation in the ventral, but not dorsal, hippocampus of males. In the female, G-1 increased the ERK activation solely in the dorsal hippocampus, independent of state anxiety. This is the first study to report an anxiolytic effect of GPR30 activation in male mice, in a rapid time frame that is commensurate with non-genomic signaling by estrogen. PMID- 24240012 TI - pH-responsive zwitterionic copolypeptides as charge conversional shielding system for gene carriers. AB - A novel rapid pH-responssive polymer polyethylenimine-poly(l-lysine)-poly(l glutamic acid) (PELG) was designed as the shielding system. The zwitterionic copolypeptide PELG with negatively charged at physical pH can act as the shielding system to shield positively charged polyplexes. PELG was used to shield PEI25k/DNA to form ternary polyplex, the polyplex surface zeta potential can change from a negative to positive nearly pH value of 6.9. Because the pH value of tumor extracellular environment is about 6.5, the positive charges on the polyplexes could be restored in tumors, which is beneficial to the electrostatic interactions between positive polyplexes and negative tumor cells, leading to high cell uptake efficiency and high transfection efficiency. PMID- 24240013 TI - Phage-display library biopanning and bioinformatic analysis yielded a high affinity peptide to inflamed vascular endothelium both in vitro and in vivo. AB - Vascular inflammation is considered the primary pathological condition occurring in many chronic diseases. To detect the inflamed endothelium via imaging analysis or guide the drug to target lesions is therefore important for early diagnosis and treatment of vascular inflammatory diseases. In this study, we obtained a novel peptide NTTTH through high throughout biopanning and bioinformatic analysis. In vitro studies indicated that NTTTH homologs could especially target inflamed vascular endothelial cells, as imaging quantitative analysis indicated that the mean of integrated optical density (MIOD) and mean of stained area (MSA) were significantly higher versus control (P<0.05). In vivo studies showed that, after intravenous injection of enhanced green fluorescent protein (EGFP)-labeled NTTTH homologs into the lipopolysaccharide (LPS)-inflamed mice for 30min, NTTTH homologs were distributed in highly vascularized and inflamed organs like liver and kidney. As a control, little fluorescence could be detected in mice injected with EGFP alone. Cryosection showed that NTTTH homologs especially targeted inflamed vasculatures but not normal ones. We did not detect fluorescence signal in either normal or inflamed mice which were injected with EGFP alone. The results suggested the role of NTTTH homologs in guiding the targeted binding of EGFP to inflamed vasculature and the potential usage for imaging detection and drug delivery. PMID- 24240014 TI - Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis. AB - Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in adipose tissue engineering due to their high biocompatibility and adipogenic inductive property. However, previous studies involving DAT-derived scaffolds have not fully revealed their potentials for in vivo adipose tissue construction. With the aim of developing a more efficient adipose tissue engineering technique based on DAT, in this study, we investigated the in vivo adipogenic potential of a basic fibroblast growth factor (bFGF) delivery system based on heparinized DAT (Hep-DAT). To generate this system, heparins were cross-linked to mouse DATs by using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-Hydroxysuccinimide. The bFGF-binding Hep-DATs were first tested for controlled release ability in vitro and then transplanted subcutaneously. Highly vascularized adipose tissues were formed 6weeks after transplantation. Histology and gene expression analysis revealed that majority of the Hep-DAT scaffolds were infiltrated with host derived adipose tissues that possessed similar adipogenic and inflammatory gene expression as endogenous adipose tissues. Additionally, strong de novo adipogenesis could also be induced when bFGF-binding Hep-DATs were thoroughly minced and injected subcutaneously. In conclusion, our study demonstrated that bFGF-binding Hep-DAT could be an efficient, biocompatible and injectable adipogenic system for in vivo adipose tissue engineering. PMID- 24240015 TI - The development of an in vitro assay to screen lipid based nanoparticles for siRNA delivery. AB - In order to rapidly screen and select lead candidates for in vivo evaluation of lipid nanoparticles (LNPs) for systemic small interfering RNA (siRNA) delivery, an in vitro assay amenable to high-throughput screening (HTS) is developed. The strategy is to mimic the in vivo experience of LNPs after systemic administration, such as interactions with serum components, exposure to endosomal pH environments, and interactions with endosomal membrane lipids. It is postulated that the amount of siRNA released from LNPs after going through these treatments can be used as a screening tool to rank order the effectiveness of siRNA delivery by lipid nanoparticles in vivo. LNPs were incubated with 50% serum from different species (i.e. mouse, rat, or rhesus) at 37 degrees C. The resulting samples were then reacted with anionic, endosomal-mimicking lipids at different pHs. The amount of siRNA released from LNPs was determined using spectrophotometry employing the fluorescent indicator SYBR Gold. Our results indicated that the amount of siRNA liberated was highly dependent upon the species of serum used and the pH to which it was exposed. LNPs treated with mouse serum showed higher levels of siRNA release, as did those subjected to endosomal pH (6.0), compared to physiological pH. Most interestingly, a good correlation between the amount of siRNA released and the in vivo efficacy was observed. In conclusion, an in vitro siRNA release assay was developed to screen and rank order LNPs for in vivo evaluation. PMID- 24240016 TI - Optimal autologous peripheral blood progenitor cell mobilization involves more than the CD34+yield. PMID- 24240017 TI - Intrusiveness of behavioral treatments for adults with intellectual disability. AB - The current study examined treatment intrusiveness within behavior intervention programs developed for adults with intellectual disability (ID). Behavior analysts provided demographic information about themselves, their adult clients with ID, and their clients' behavior intervention plans, and they completed an online version of the Treatment Intrusiveness Measure (Carter et al., 2009), an instrument that provides a Base Level Intrusiveness Score (BLIS; a score computed across five areas of categorization, such as, Health and Safety) and a Modified Level of Intrusiveness Score (MLIS), which assesses the presence or absence of intrusiveness-reducing practices. Among other findings, various statistical analyses revealed (a) a significant difference between BLIS and modified (BLIS minus MLIS) intrusiveness scores, (b) the practices within which most of the intrusiveness was concentrated within behavioral treatment programs, and (c) the least- and most-utilized intrusiveness-reducing practices. Implications are provided to assist professionals working with adults with ID who engage in challenging behavior and are supported through behavior intervention services. PMID- 24240018 TI - Working memory performance and executive function behaviors in young children with SLI. AB - The present study compared the performances of young children with specific language impairment (SLI) to that of typically developing (TD) children on cognitive measures of working memory (WM) and behavioral ratings of executive functions (EF). The Automated Working Memory Assessment was administered to 58 children with SLI and 58 TD children aged 4 and 5 years. Additionally, parents completed the Behavior Rating Inventory of Executive Function - Preschool Version. The results showed the SLI group to perform significantly worse than the TD group on both cognitive and behavioral measures of WM. The deficits in WM performance were not restricted to the verbal domain, but also affected visuospatial WM. The deficits in EF behaviors included problems with inhibition, shifting, emotional control, and planning/organization. The patterns of associations between WM performance and EF behaviors differed for the SLI versus TD groups. WM performance significantly discriminated between young children with SLI and TD, with 89% of the children classified correctly. The data indicate domain general impairments in WM and problems in EF behaviors in young children with SLI. Attention should thus be paid to WM - both verbal and visuospatial - and EF in clinical practice. Implications for assessment and remediation were discussed. PMID- 24240019 TI - The negative attribution processes of mothers of children with attention deficit/hyperactivity disorder. AB - The objective of this study was to investigate the attribution processes of mothers regarding children's prosocial behaviors, inattention, and hyperactivity/impulsivity (symptoms of attention deficit/hyperactivity disorder, ADHD) using two paradigms. The first paradigm involved multidimensional attributions. The second paradigm concerned making attributions of children's identical behaviors based on information such as consensus, distinctiveness, and consistency. The participants were 64 mothers of children with ADHD (7-13 years old) and 64 mothers with typical/normal children (7-12 years old). The results showed that mothers of typical children exhibited positive attribution styles or person attributions whereas mothers of children with ADHD exhibited negative attribution styles. Mothers of children with ADHD tended to make personal attributions of children's negative behaviors (e.g., inattention and hyperactivity/impulsivity; HI) but made situational attributions of prosocial behaviors. The results of this study can be used in future studies of the effects of intervention on children with ADHD or in studies related to neurophysiology. PMID- 24240020 TI - The determinants of self-determined behaviors of young children with cerebral palsy. AB - The purpose of this study was to identify determinants of self-determined behaviors of young children with cerebral palsy. The participants were 429 children (56% boys, 18-60 months) and their parents. Structural equation modeling was used to test two models of self-determined behaviors, one for children with walking mobility (Gross Motor Function Classification System, GMFCS levels I-II) and the other for children with limited self-mobility (GMFCS levels III-V). Cognitive-behavioral problems and the extent family supports their child's self determined behaviors explained 60% of the variance in self-determined behaviors of children with walking mobility. Cognitive-behavioral problems, playfulness, and the extent family supports their child's self-determined behaviors explained 68% of the variance in self-determined behaviors of children with limited self mobility. The less the child's cognitive-behavioral problems affect daily activities (p<.05) and the more the extent family supports their child's self determined behaviors (p<.05), the more effective the child's self-determined behaviors. Playfulness only had an effect on self-determined behaviors of children with limited self-mobility (p<.05). Service providers are encouraged to assess and support children's daily functioning in cognition, communication, and emotional/behavioral regulation, playfulness, and family strategies in providing opportunity for children to practice self-determined behaviors. PMID- 24240021 TI - A category 1 EQA scheme for comparison of laboratory performance and method performance: An international pilot study in the framework of the Calibration 2000 project. AB - INTRODUCTION: In the modern healthcare service, patients receive care in multiple hospitals and healthcare settings. Therefore, harmonization of results from different methods and instruments, both between and within laboratories, is of the utmost importance. The present pilot study aims to test the use of a Category 1 EQA scheme across four European countries by assessing the current level of equivalence of test results. METHOD: This work was led by the Dutch External Quality Assurance Scheme SKML and involved 28 laboratories from three regions in the UK, Spain and Portugal, and 120 laboratories from The Netherlands. A set of six commutable samples, targeted with reference methods, were circulated and 18 biochemistry analytes were tested. RESULTS AND CONCLUSIONS: The Total Error (TE) score, defined as the probability (%) that results are within the Total Error Acceptable (TEA) limits, for the eighteen analytes was calculated. Our data show that there is a need for further harmonization of laboratory data, in particular for electrolytes (calcium, chloride, magnesium, sodium), enzymes (ALT, amylase, AST, LDH), lipids (HDL-cholesterol), and for substrates (creatinine, total protein). Lack of performance consistency between instruments was seen for most analytes. The lack of harmonization is still present despite manufacturer claims of established traceability. PMID- 24240023 TI - Amputee socks: thickness of multiple socks. AB - BACKGROUND AND AIM: It is unclear how total sock ply and thickness are related when more than one sock is worn. The objectives were to determine whether the thickness of one multi-ply amputee sock of ply P was the same as the thickness of a stack of reduced-ply socks of total ply P, and whether the thickness of N single socks stacked one on top of the other was equal to the sum (1 to N) of the single sock thicknesses. TECHNIQUE: Using a custom instrument, compressive stresses were applied while sock thickness was measured. DISCUSSION: The thickness of one multi-ply sock of ply P was typically less than the thickness of a stack of reduced-ply socks of total ply P. The thickness of N single socks stacked one on top of the other was approximately equal to the sum (1 to N) of the single sock thicknesses. CLINICAL RELEVANCE: Our findings suggest three 1-ply socks to be 20% greater in thickness than one 3-ply sock, and one 3-ply + two 1 ply socks to be 30% greater in thickness than one 5-ply sock. PMID- 24240022 TI - Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain. AB - Preterm birth is very strongly associated with maternal/foetal inflammation and leads to permanent neurological deficits. These deficits correlate with the severity of white matter injury, including maturational arrest of oligodendrocytes and hypomyelination. Preterm birth and exposure to inflammation causes hypothyroxinemia. As such, supplementation with thyroxine (T4) seems a good candidate therapy for reducing white matter damage in preterm infants as oligodendrocyte maturation and myelination is regulated by thyroid hormones. We report on a model of preterm inflammation-induced white matter damage, in which induction of systemic inflammation by exposure from P1 to P5 to interleukin-1beta (IL-1beta) causes oligodendrocyte maturational arrest and hypomyelination. This model identified transient hypothyroidism and wide-ranging dysfunction in thyroid hormone signalling pathways. To test whether a clinically relevant dose of T4 could reduce inflammation-induced white matter damage we concurrently treated mice exposed to IL-1beta from P1 to P5 with T4 (20 MUg/kg/day). At P10, we isolated O4-positive pre-oligodendrocytes and gene expression analysis revealed that T4 treatment did not recover the IL-1beta-induced blockade of oligodendrocyte maturation. Moreover, at P10 and P30 immunohistochemistry for markers of oligodendrocyte lineage (NG2, PDGFRalpha and APC) and myelin (MBP) similarly indicated that T4 treatment did not recover IL-1beta-induced deficits in the white matter. In summary, in this model of preterm inflammation-induced white matter injury, a clinical dose of T4 had no therapeutic efficacy. We suggest that additional pre-clinical trials with T4 covering the breadth and scope of causes and outcomes of perinatal brain injury are required before we can correctly evaluate clinical trials data and understand the potential for thyroid hormone as a widely implementable clinical therapy. PMID- 24240024 TI - Timing of surgical intervention in cauda equina syndrome: a systematic critical review. AB - OBJECTIVE: Cauda equina syndrome (CES) is a rare but important neurosurgical emergency. Despite being a recognized clinical entity since 1934, there remains significant uncertainty in the literature regarding the urgency for surgical intervention. The past decade has seen the emergence of the much-referred-to 48 hour limit as a possible window of safety. The ramifications of this time point are significant for early patients who may subsequently have urgent treatment delayed, and for litigation cases, after which adverse decisions are more likely to occur. METHODS: A systematic principally qualitative review of the animal and human clinical literature is presented, examining the evidence for urgent surgical decompression in CES and the much-quoted 48-hour rule. RESULTS: There is significant discordance in the literature regarding whether emergency surgery improves outcomes; however, a growing consensus is the acknowledgment that biologic systems deteriorate in a continuous rather than stepwise manner. Level of neurological dysfunction at surgery (incomplete CES vs. CES with retention) is probably the most significant determinant of prognosis. Onset and duration of symptoms also are likely to have an impact, if not on overall outcome then at least on duration of neurological recovery. CONCLUSIONS: There is no strong basis to support 48 hours as a blanket safe time point to delay surgery. Both early and delayed surgery may result in improved neurological outcomes. However, it is likely that the earlier the surgical intervention, the more beneficial the effects for compressed nerves, especially with acute neurological compromise. PMID- 24240025 TI - Outcomes of a nontransfer protocol for mild traumatic brain injury with abnormal head computed tomography in a rural hospital setting. AB - OBJECTIVE: This study sought to investigate outcomes after a novel nontransfer protocol for mild traumatic brain injuries patients with small intracranial hemorrhage (ICH) in a rural trauma center without neurosurgical capabilities. METHODS: This was a retrospective cohort study. In 2007, a nontransfer protocol was implemented at a Level III Trauma Center. It included adult patients from April 2007 through December 2012 with mild traumatic brain injury (mTBI) (Glasgow Coma Scale score 13 to 15) and computed tomography (CT) showing small ICH and no coagulopathy. The following ICHs were allowed: 1) minimal or small traumatic subarachnoid hemorrhage, 2) punctuate or minimal superficial cerebral contusion, 3) punctuate or minimal intraparenchymal hemorrhage, or 4) very small subdural hemorrhage (SDH) without mass effect (a very thin smear SDH along the tentorium or falx). CT scans were reviewed by the on-call neurosurgeon at an affiliated Level I Trauma Center, and consensus was obtained on the suitability for nontransfer. RESULTS: A total of 76 patients were included. The median hospital length of stay was 1 day (interquartile range = 1 day). No patient required a neurosurgical intervention or postadmission transfer to a Level I facility. There were no in-hospital deaths, and all patients were discharged with stable head CTs and in good neurologic condition. Two patients were readmitted for nonprotocol related reasons: 1 acute-on-chronic SDH 6 weeks postdischarge, and 1 visual eye change with normal CT 2 days postdischarge. CONCLUSIONS: Our 6-year study corroborates the low neurosurgical rate reported in the literature for mTBI with small ICH. Nontransfer protocols may lead to a more efficient use of hospital resources while providing safe, effective and economical health care. PMID- 24240027 TI - Divergence-based framework for common spatial patterns algorithms. AB - Controlling a device with a brain-computer interface requires extraction of relevant and robust features from high-dimensional electroencephalographic recordings. Spatial filtering is a crucial step in this feature extraction process. This paper reviews algorithms for spatial filter computation and introduces a general framework for this task based on divergence maximization. We show that the popular common spatial patterns (CSP) algorithm can be formulated as a divergence maximization problem and computed within our framework. Our approach easily permits enforcing different invariances and utilizing information from other subjects; thus, it unifies many of the recently proposed CSP variants in a principled manner. Furthermore, it allows to design novel spatial filtering algorithms by incorporating regularization schemes into the optimization process or applying other divergences. We evaluate the proposed approach using three regularization schemes, investigate the advantages of beta divergence, and show that subject-independent feature spaces can be extracted by jointly optimizing the divergence problems of multiple users. We discuss the relations to several CSP variants and investigate the advantages and limitations of our approach with simulations. Finally, we provide experimental results on a dataset containing recordings from 80 subjects and interpret the obtained patterns from a neurophysiological perspective. PMID- 24240026 TI - Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms. AB - Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1beta, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARgamma pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1beta axis as a potential therapeutic target for this presently incurable disease. PMID- 24240028 TI - Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia. AB - Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 degrees C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 degrees C; 60 h). The results showed that at 4 degrees C the viability was maintained above 80% for 48 h, at 8 degrees C decreased slightly, whereas at room temperature and 37 degrees C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1*10(6) cells/mL, which must be stored at 4 degrees C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h. PMID- 24240030 TI - Perceptual and processing differences between physical and dichorhinic odor mixtures. AB - Perceptual integration of sensory input from our two nostrils has received little attention in comparison to lateralized inputs for vision and hearing. Here, we investigated whether a binary odor mixture of eugenol and l-carvone (smells of cloves and caraway) would be perceived differently if presented as a mixture in one nostril (physical mixture), vs. the same two odorants in separate nostrils (dichorhinic mixture). In parallel, we investigated whether the different types of presentation resulted in differences in olfactory event-related potentials (OERP). Psychophysical ratings showed that the dichorhinic mixtures were perceived as more intense than the physical mixtures. A tendency for shift in perceived quality was also observed. In line with these perceptual changes, the OERP showed a shift in latencies and amplitudes for early (more "sensory") peaks P1 and N1 whereas no significant differences were observed for the later (more "cognitive") peak P2. The results altogether suggest that the peripheral level is a site of interaction between odorants. Both psychophysical ratings and, for the first time, electrophysiological measurements converge on this conclusion. PMID- 24240031 TI - Wearable monitoring for mood recognition in bipolar disorder based on history dependent long-term heart rate variability analysis. AB - Current clinical practice in diagnosing patients affected by psychiatric disorders such as bipolar disorder is based only on verbal interviews and scores from specific questionnaires, and no reliable and objective psycho-physiological markers are taken into account. In this paper, we propose to use a wearable system based on a comfortable t-shirt with integrated fabric electrodes and sensors able to acquire electrocardiogram, respirogram, and body posture information in order to detect a pattern of objective physiological parameters to support diagnosis. Moreover, we implemented a novel ad hoc methodology of advanced biosignal processing able to effectively recognize four possible clinical mood states in bipolar patients (i.e., depression, mixed state, hypomania, and euthymia) continuously monitored up to 18 h, using heart rate variability information exclusively. Mood assessment is intended as an intrasubject evaluation in which the patient's states are modeled as a Markov chain, i.e., in the time domain, each mood state refers to the previous one. As validation, eight bipolar patients were monitored collecting and analyzing more than 400 h of autonomic and cardiovascular activity. Experimental results demonstrate that our novel concept of personalized and pervasive monitoring constitutes a viable and robust clinical decision support system for bipolar disorders recognizing mood states with a total classification accuracy up to 95.81%. PMID- 24240029 TI - Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA. AB - Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders. PMID- 24240032 TI - Automated detection of perturbed cardiac physiology during oral food allergen challenge in children. AB - This paper investigates the fully automated computer-based detection of allergic reaction in oral food challenges using pediatric ECG signals. Nonallergic background is modeled using a mixture of Gaussians during oral food challenges, and the model likelihoods are used to determine whether a subject is allergic to a food type. The system performance is assessed on the dataset of 24 children (15 allergic and 9 nonallergic) totaling 34 h of data. The proposed detector correctly classified all nonallergic subjects (100% specificity) and 12 allergic subjects (80% sensitivity) and is capable of detecting allergy on average 17 min earlier than trained clinicians during oral food challenges, the gold standard of allergy diagnosis. Inclusion of the developed allergy classification platform during oral food challenges recorded would result in a 30% reduction of doses administered to allergic subjects. The results of study introduce the possibility to halt challenges earlier which can safely advance the state of clinical art of allergy diagnosis by reducing the overall exposure to the allergens. PMID- 24240033 TI - Malaria elimination: needs assessment and priorities for the future. AB - When the World Health Organization announced the goal of global eradication of malaria in 2007, questions were raised about the naivety of this proposition. Since then, experts have been divided about this goal. Some scientists suggest that when defeating malaria, elimination is a worthy and challenging aim, but this has to be done with modesty and thorough analysis. Others believe that it is time to repeat the experience of smallpox eradication and to open a whole new era for public health, the eradication of many diseases. The opposing view suggests that raising expectations and failing again may set malaria control back, rather than advance its cause. This literature review focuses on malaria elimination. It summarizes the history of malaria elimination, its success factors and reasons for failure, and the controversial issues in malaria elimination. The collected articles on the challenges of elimination, and the technical and financial feasibility that countries must appreciate before proceeding, are identified. Also, this review discusses the current global strategy to eliminate malaria and highlights the main concerns for future plans aimed at elimination. These plans foresee improving currently available diagnostic methods, therapeutic and prophylactic agents and protocols, vector control procedures, vaccine development progress, and other operational tools and approaches. Finally, this review addresses a number of research priorities in the present stage of the fight against malaria. PMID- 24240034 TI - Enteric fever burden in North Jakarta, Indonesia: a prospective, community-based study. AB - INTRODUCTION: We undertook a prospective community-based study in North Jakarta, Indonesia, to determine the incidence, clinical characteristics, seasonality, etiologic agent, and antimicrobial susceptibility pattern of enteric fever. METHODOLOGY: Following a census, treatment centre-based surveillance for febrile illness was conducted for two-years. Clinical data and a blood culture were obtained from each patient. RESULTS: In a population of 160,261, we detected 296 laboratory-confirmed enteric fever cases during the surveillance period, of which 221 (75%) were typhoid fever and 75 (25%) were paratyphoid fever. The overall incidence of typhoid and paratyphoid cases was 1.4, and 0.5 per thousand populations per year, respectively. Although the incidence of febrile episodes evaluated was highest among children under 5 years of age at 92.6 per thousand persons per year, we found that the burden of typhoid fever was greatest among children between 5 and 20 years of age. Paratyphoid fever occurred most commonly in children and was infrequent in adults. CONCLUSION: Enteric fever is a public health problem in North Jakarta with a substantial proportion due to paratyphoid fever. The results highlight the need for control strategies against enteric fever. PMID- 24240035 TI - Antimicrobial resistance among blood culture isolates of Salmonella enterica in New Delhi. AB - INTRODUCTION: Enteric fever is a global public health problem, especially in developing countries. Antimicrobial resistance is a major issue enteric fever management. This study examined current pattern of antimicrobial susceptibility among Salmonella enterica isolates from enteric fever cases at a tertiary care centre in New Delhi, India. METHODOLOGY: Blood cultures from patients with enteric fever during January 2010- July 2012 were processed using the BACTEC automated system. Antimicrobial susceptibility was tested using Kirby Bauer's disc diffusion method and/or Phoenix 100 automated system. RESULTS: Of 344 isolates of Salmonella enterica, 266 (77.3%) were S. Typhi, 77 (22.4%) were S. Paratyphi A, and one (0.3%) was S. Paratyphi B. Resistance to nalidixic acid (NA(R)) (96.7%) was most common, followed by ciprofloxacin (37.9%), and azithromycin (7.3%). Multi-drug resistance was observed only in S. Typhi (3.4%). Among NA(R) strains, 61.8% were sensitive, 11.1% were moderately sensitive, and 23.9% were resistant to ciprofloxacin (0.8%, 57.4%, and 37.9% respectively according to revised CLSI breakpoint criteria for ciprofloxacin). Resistance to third-generation cephalosporin was found in seven (2%) strains of S. enterica. CONCLUSION: Increasing rates of nalidixic acid, fluoroquinolone and azithromycin resistance among S. enterica, particularly in S. Paratyphi A strains, is of concern, as S. Paratyphi A infection is becoming increasingly common and is not prevented by current vaccinations. Our results favour use of cefexime or possibly chloramphenicol as first choice for uncomplicated enteric fever. MICs for third generation cephalosporins and susceptibility pattern must be closely monitored in view of its emerging resistance among Salmonella enterica. PMID- 24240036 TI - Fluoroquinolone resistant mechanisms in methicillin-resistant Staphylococcus aureus clinical isolates in Cairo, Egypt. AB - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a persistent problem in community and health care settings. Fluoroquinolones are among the drugs of choice used to treat MRSA infections. This study aims to identify different mechanisms of fluoroquinolne resistance in local MRSA random sampling isolates in Cairo, Egypt. METHODOLOGY: A total of 94 clinical isolates of S. aureus were collected from two major University hospitals in Cairo. Identification was confirmed by appropriate morphological, cultural, and biochemical tests. The antibiotic susceptibility pattern was determined for all isolates. The possible involvement of efflux pumps in mediating fluoroquinolone resistance as well as changes in the quinolone resistance determining region (QRDR) of gyrA and gyrB genes were investigated RESULTS: A total of 45 isolates were found to be MRSA, among which 26 isolates were found to be fluoroquinolone resistant. The MIC values of the tested fluoroquinolones in the presence of the efflux pump inhibitors omeprazole and piperine were reduced. Measuring the uptake of ciprofloxacin upon the addition of the efflux pump inhibitor omeprazole, an increased level of accumulation was observed. Non-synonymous and silent mutations were detected in the QRDR of gyrA and gyrB genes. CONCLUSIONS: These results shed light on some of the resistance patterns of MRSA strains isolated from local health care settings in Cairo, Egypt. The resistance of these MRSA towards fluoroquinolones does not depend only on mutation in target genes; other mechanisms of resistance such as the permeability effect, efflux pumps and decreased availability of quinolones at the target site can also be involved. PMID- 24240037 TI - Prevalence and characterization of extended spectrum beta-lactamase-producing Enterobacter cloacae strains in Algeria. AB - INTRODUCTION: Expended spectrum beta-lactamase (ESBL)-producing Enterobacter cloacae is an important nosocomial pathogen. In this study, the prevalence and the molecular epidemiology of ESBL producing E. cloacae strains isolated from various hospitals in Annaba, Algeria were investigated. METHODOLOGY: The study involved 63 isolates of E. cloacae obtained during 2009 at the four hospitals in Annaba. The detection of ESBL was performed using the double-disk synergy test and the combined disk test. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. The presence of bla(CTX-M), bla(SHV), bla(TEM), and bla(DHA) beta-lactamase genes was evaluated by PCR, and genomic typing was determined by pulsed-field gel electrophoresis (PFGE) analysis. The clinical and microbiological data were entered into the EpiI Info database. RESULTS: Thirty isolates (47.6%) had an ESBL phenotype. Bla(CTX-M) group1 (76%); bla(TEM) (70%) were the most prevalent, followed by bla(DHA) (16.6%) and bla(SHV) (10%). Eighteen strains expressed at least two bla genes. MICs revealed a high level of resistance to cefotaxime, ceftazidime, and cefepime. PFGE revealed an epidemic clonal dissemination of these isolates. Various risk factors associated with the occurrence of ESBL-producing E. cloacae were detected. CONCLUSIONS: A higher frequency of ESBL-producing isolates and a diversity of beta-lactamases were detected among ESBL-producing E. cloacae; these resulted from an epidemic clonal dissemination and high transference of ESBL genes between bacteria in hospital settings. Strict measures will be required to control the further spread of these pathogens in hospital settings. PMID- 24240038 TI - Escherichia coli and Salmonella spp. in meat in Jeddah, Saudi Arabia. AB - INTRODUCTION: Food-borne pathogens are the leading cause of illness and death in developing countries, killing approximately 1.8 million people annually. In developed countries, food-borne pathogens are responsible for millions of cases of infectious gastrointestinal diseases each year, costing billions of dollars. The objective of this study was to screen for two major food-borne pathogens, Escherichia coli and Salmonella spp., from meat samples obtained from different strata of the consumer market in Jeddah. METHODOLOGY: A total of 60 meat samples, 20 each from large hypermarkets, groceries and small butcher shops were used in the study. Samples were transported to the laboratory in a cooler. They were macerated in peptone water and then seeded on selective media appropriate for each organism. Colonies were identified using conventional microbiological methods and suspected colonies were confirmed as E. coli and Salmonella spp. by polymerase chain reaction (PCR) using specific primers. RESULTS: The results indicated a high degree of contamination in samples from butcher shops as compared to those from groceries or hypermarkets (high scale supermarkets). Both pathogens E. coli and Salmonella spp. were found in higher rates in the samples from butcher shops. In small butcher shops, E. coli was found at an incidence of 65%, and Salmonella at 45%. CONCLUSION: The results indicate an urgent need for applying proper food hygienic practices in food outlets, especially in small ones, to reduce the incidence of food-borne diseases. Vigilance by the right agencies must be implemented in order to prevent future food-borne outbreaks. PMID- 24240039 TI - Diversity of Moraxella spp. strains recovered from infectious bovine keratoconjunctivitis cases in Uruguay. AB - BACKGROUND: Infectious bovine keratoconjunctivitis (IBK) is the most common ocular disease that affects cattle throughout the world and it has a very significant economic impact. IBK is caused by members of the genus Moraxella and therapeutic and preventive measures have shown limited success. Vaccines, most of them chemically inactivated bacterins, generally induce a limited protection. METHODOLOGY: In this study, the genetic diversity of Uruguayan clinical Moraxella bovis and Moraxella bovoculi isolates was assessed by RAPD-PCR, ERIC-PCR and BOX PCR fingerprinting. Also, antibiotic resistance of the Moraxella spp. isolates was assessed utilizing the disk diffusion method. RESULTS: When interspecific molecular diversity was assessed, different bands patterns were observed even within a single outbreak of IBK, showing the coexistence of different genotypes of Moraxella spp. The high genetic diversity within M. bovis and M. bovoculi isolates did not permit to correlate isolates DNA fingerprints with geographical origins, dates or even with both different Moraxella species. Antibiotics resistance patterns showed significant differences between M. bovis and M. bovoculi. CONCLUSIONS: This is the first study of diversity that includes M. bovis and M. bovoculi associated to IBK cases. Genetic diversity did not allow to correlate DNA fingerprints of the isolates with geographical origins, isolation dates or even both different Moraxella species. Antibiotics resistance patterns showed differences between M. bovis and M. bovoculi. This remarkable variation within isolates could explain the partial protection induced by commercial vaccines. All these findings could be important for the design of prevention or treatment strategies against IBK. PMID- 24240040 TI - Susceptibility of clinical methicillin-resistant Staphylococci isolates to new antibiotics. AB - BACKGROUND: The treatment of methicillin-resistant staphylococcal infections has been a growing problem both in and out of hospitals for the past 30 years. Therefore, there is a need for other antibiotics as an alternative to glycopeptides in the treatment of methicillin-resistant staphylococcal infections. This study investigated the in vitro susceptibility of 49 methicillin resistant Staphylococcus aureus (MRSA) and 59 methicillin-resistant coagulase negative staphylococci (MRCNS) clinical isolates to daptomiycin, telithromycin, tigecyclin, quinupristin/dalfopristin, and linezolid. METHODOLOGY: The identification of the strains was made by conventional methods. Antibiotic susceptibility tests were performed according to CLSI. Methicillin resistance was determined by cefoxitin disk. Susceptibilities of the strains to daptomycin, quinupristin/dalfopristin, tigecycline, and vancomycin were performed using the E test according to the recommendations of CLSI 2011 and the manufacturer. RESULTS: Two strains of MRCNS were resistant, and one was teicoplanin intermediate. It was found that one (2%) strain of MRSA and two (3%) strains of MRCNS were resistant to tigecyclin. Telithromycin resistance was detected in 33% of MRSA strains and 37% of MRCNS strains. Inducible clindamycin resistance was found in nine (18.4%) strains of MRSA and eighteen (30.5%) strains of MRCNS. All strains were susceptible to daptomiycin, quinupristin/dalfopristin, and linezolid. CONCLUSIONS: Although it has recently been used, telithromycin has a high percentage of resistance; its use for methicillin-resistant staphylococcal strains, therefore, should be limited. Daptomycin and quinupristin/dalfopristin were found to be effective against MRSA and MRCNS strains and were concluded to be a good choice in the treatment of methicillin-resistant staphylococci. PMID- 24240041 TI - Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India. AB - INTRODUCTION: The epidemiology of viral hepatitis during pregnancy is of paramount importance for health planners and program managers. Data on viral hepatitis during pregnancy are not readily available. This study was conducted to assess the extent of seropositivity of hepatitis B, hepatitis C, HIV, and syphilis in pregnant women and to re-evaluate the need for routine antenatal care screening. METHODOLOGY: All samples were tested to detect HBsAg by enzyme linked immunosorbent assay (ELISA). Samples were tested to detect anti-HCV by ELISA. Samples were also tested for antibodies to Treponema Pallidum by qualitative rapid plasma reagine (RPR); finally, samples were tested for antibodies to HIV by three different methods as per Strategy III of the National AIDS Control Organization by using different systems of testing to establish a diagnosis of HIV. RESULTS: Seropositivity of hepatitis B was 2.9%, hepatitis C was 0.19%, syphilis was 0.48%, and HIV was 0.38%. Out of the 1038 samples, no co-infection was found between hepatitis B, hepatitis C, syphilis, or HIV. CONCLUSION: The data from this study can help health professionals to treat antenatal patients more effectively. The data also reinforces the need for establishing effective prevention programs, which could lead to a reduction in the prevalence of HBV, HCV, syphilis, and HIV. PMID- 24240042 TI - Recent trends in HIV prevalence in a remote setting of southern India: insights into arranging HIV control policies. AB - INTRODUCTION: Constant vigilance of the dynamics of HIV prevalence is important in estimating, regulating, and implementing prevention programs. The objective of this study was to investigate the trend in the prevalence of HIV infection over six years among specific demographic groups in the remote district of southern India. METHODOLOGY: All high-risk attendees of the Integrated Counseling and Testing Centre, Government Theni Medical College between April 2005 and December 2010 were included in this study. Characteristics including age, sex, place of residence, literacy, and HIV sero-status were collected as per the guidelines of the National AIDS Control Organization. RESULTS: A total of 50,043 data sets were analyzed; 3,282 (6.6%) tested positive for HIV infection. The prevalence of HIV infection among the <= 25 age group was significantly lower as compared to the elderly (4.4% vs. 6.9%; odds ratio 0.62; 95% confidence interval 0.55-0.71; p < 0.01). There was a decline in HIV prevalence among both age groups (P(trend) < 0.01 for <= 25 year-old; -82.3% and P(trend) < 0.01 for > 25-year old, -14.2%), males (P(trend) < 0.01; -50.9%), the urban population (P(trend) < 0.01; -45.9%), and illiterates (P(trend) < 0.01; -68%). The trend of HIV prevalence among females (P(trend) = 0.48; +9.1%), the rural population (P(trend) = 0.95; -7.1%), and literate population (P(trend) = 0.44; +28%) was statistically insignificant. CONCLUSION: HIV prevalence is stable in the female population, while it is decreasing in male population, indicating that current interventions must be strengthened to reduce HIV prevalence among females. PMID- 24240043 TI - Provider-initiated vs. client-initiated HIV testing in Autonomous Province of Vojvodina, Serbia, 2000-2008. AB - BACKGROUND: This paper describes the changes in Human Immundodeficiency virus (HIV) testing rates in Autonomous Province (AP) Vojvodina, Serbia since 2000 and compares provider-initiated with client-initiated HIV testing. METHODOLOGY: Between 2000 and 2008, 66,327 HIV screening tests were reported from AP Vojvodina. During this time HIV testing rates increased from 1.2 per 1,000 inhabitants in 2000, to 7.7 per 1,000 inhabitants in 2008. RESULTS: The results showed an increase in testing as a consequence of increased mandatory testing of surgical patients as well as an upsurge in the use of Voluntary Counselling and Testing (VCT). Pregnant women that were tested represented less than 5% of the overall sample population. CONCLUSION: Public health efforts in AP Vojvodina to increase HIV testing rates lead to a continuous increase in testing rates, but with different limitations. HIV testing in low prevalence middle income countries could be highly affected by procurement difficulties, low motivation of medical professionals to initiate testing, and opportunities for testing limited to large towns and cities. PMID- 24240044 TI - Relation of interleukin-1beta gene to treatment response in chronic patients infected with HCV genotype 4. AB - INTRODUCTION: Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 70% of infected patients, while 20-30% of patients recover spontaneously. This strengthens the role of the host genetic factors in either spontaneous or drug-induced viral clearance. The aim of this study was to investigate the relationship between interleukin-1beta +3953 gene polymorphism and the response to interferon therapy in chronic HCV patients infected with genotype 4. METHODOLOGY: The interleukin-1beta (+3953 C/T) (rs1143634) gene was amplified in 115 chronic HCV patients. Interleukin-1beta single nucleotide polymorphism (SNP) plus several clinical and pathological factors were statistically analyzed in correlation with response to therapy. RESULTS: Genotypes C/T and T/T had a significant association with non-response to treatment compared to genotype C/C, which had a strong association with response to treatment (95% confidence; 6.4884-48.5818, p = 0.0001). Furthermore, analysis of allele frequency in this cohort revealed that the T allele is associated with non-response, higher fibrosis, and higher hepatic activity, while the C allele had a significant association with sustained virologic response lower fibrosis, and lower hepatic activity (p value = 0.0001). CONCLUSION: This is the first study to examine the correlation between interleukin-1beta (+3953 C/T) (rs1143634) gene polymorphism and the response of interferon therapy in genotype 4 HCV-infected patients. The results encourage further assessment of this SNP as a marker to predict response to therapy and disease progression, which can have major implications in saving money, time, and in avoiding unnecessary adverse effects. PMID- 24240046 TI - Prevalence of parasitic infections in HIV-positive patients in southern Ethiopia: a cross-sectional study. AB - INTRODUCTION: Intestinal parasitic infections are a major public health burden in tropical countries. Although all HIV/AIDS patients are susceptible to parasitic infections, those having lower immune status are at greater risk. The aim of this study was to determine the prevalence of intestinal parasitic infections in patients living with HIV/AIDS. METHODOLOGY: This was a facility-based cross sectional study. A total of 343 consecutively sampled HIV/AIDS patients from the HIV care clinic of Hawassa University Referral Hospital were included. Subjects were interviewed for demographic variables and diarrheal symptoms using structured questionnaires. Stool examinations and CD4 cells counts were also performed. RESULTS: The prevalence of intestinal parasitic infection was 47.8% among HIV/AIDS patients; single helminthic infection prevalence (22.7%) was higher than that the prevalence of protozoal infections (14.6%). About 54% of study participants had chronic diarrhea while 3.4% had acute diarrhea. The prevalence of intestinal parasites in patients with chronic diarrhea was significantly higher than in acute diarrhea (p <0.05). Non-opportunistic intestinal parasite infections such as Ascaris lumbricoides, Taenia spp., and hookworm were commonly found, regardless of immune status or diarrheal symptoms. Opportunistic and non-opportunistic intestinal parasitic infection were more frequent in patients with a CD4 count of <200/mm(3) (OR=9.5; 95% CI: 4.64-19.47) when compared with patients with CD4 counts of >=500 cells/mm(3). CONCLUSIONS: Intestinal parasitic infections should be suspected in HIV/AIDS-infected patients with advanced disease presenting with chronic diarrhea. Patients with low CD4 counts should be examined critically for intestinal parasites, regardless of diarrheal status. PMID- 24240045 TI - Endogenous IFNgamma in chronic HCV genotype 4 patients treated with PEG-IFNalpha and ribavirin. AB - INTRODUCTION: Hepatitis C virus (HCV) infections remain an increasingly prevalent and emergent health problem worldwide, causing a wide spectrum of liver diseases. Combination therapy with pegylated interferon (PEG-IFN) of peginterferon alfa-2a and oral ribavirin is currently recognized as the standard treatment of chronic HCV infection. Several complex immunological mechanisms are involved during the course of HCV treatment using interferons. The role of endogenous interferon gamma (IFNgamma) in Egyptian patients infected with chronic HCV and treated with PEG-IFN/ribavirin is uncertain. The goal of this study was to evaluate the association of IFNgamma and chronic HCV infection among patients treated with combination therapy of PEG-IFN/ribavirin. METHODOLOGY: Samples from 20 patients infected with HCV genotype-4 (HCV-4) and 20 non-infected individuals as healthy controls were used in this retrospective study. IFNgamma levels in peripheral blood monocytes were analyzed, along with liver enzyme alanine aminotransferase (ALT) levels, and single nucleotide polymorphism (SNP) of the myxovirus resistance-A (MxA) gene. RESULTS: The results showed that an increase of IFNgamma and a decrease of ALT levels in chronic HCV-infected patients after 12 weeks of treatment with combination therapy. CONCLUSION: Enhanced IFNgamma secretion and decreased liver enzyme ALT production are indicative of HCV clearance and improvement of liver function. In addition, the SNP of the MxA gene is an important host genetic factor that independently influenced the response to IFNalpha in patients with chronic HCV infection, especially in those with a low viral load. PMID- 24240047 TI - Critical evaluation of antimicrobial use--a Turkish university hospital example. AB - INTRODUCTION: Antimicrobials are being used unnecessarily for different reasons. The aims of this study were: assessment of the quality of antimicrobial use and determination of the factors related to correct use. METHOD: Antimicrobial practice at Dicle University Hospital (DUH) was evaluated with a point prevalence approach. Using a standardized data collection form, the patients' data (clinic, epidemiology, laboratory and antimicrobial use) was collected. Possible influential factors on antimicrobial use were examined. RESULTS: In the surveillance study 1,350 inpatients were evaluated; 461 (34.1%) of them were using antimicrobials for treatment and 187 (13.9%) for prophylaxis. Antimicrobial indication was found in 355 of 461 patients (77.0%), and the number of antimicrobials was 1.8 per patient in the treatment group. The most common reason for antimicrobial use was community-acquired infection (57.9%). Pneumonia (20.4%), skin and soft tissue infections (9.11%) and urinary tract infections (7.9%) were the most common infectious diseases. Positive culture results were available for 39 patients (8.5.0%) when antimicrobial treatment started. All steps of antimicrobial use were found appropriate in 243 patients (52.7%). In multivariate analyses, clinical manifestation of infection at the beginning (p <0.001), presence of leukocyte counting (p <0.001) and prescription by an infectious disease specialist were found significantly positive factors for wholly appropriate antimicrobial use. Hospitalization with a diagnosis other than infection was found a significantly negative factor for appropriate antimicrobial use (p=0.001). CONCLUSION: The quality of antimicrobial use could be improved with better clinical and laboratory diagnosis and consultation with infectious diseases specialists. PMID- 24240048 TI - Phenotypic characterization and colistin susceptibilities of carbapenem-resistant of Pseudomonas aeruginosa and Acinetobacter spp. AB - INTRODUCTION: Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin. METHODOLOGY: Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-beta-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest. RESULTS: Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p <0.05) more frequently resistant to the other antibiotics than carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin. CONCLUSION: Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered. PMID- 24240049 TI - Panton-Valentine leukocidin and biofilm production of Staphylococcus aureus isolated from respiratory tract. AB - INTRODUCTION: Staphylococcus aureus is one of the first bacteria colonizing in cystic fibrosis (CF) respiratory tract and different virulence factors are responsible for disease progression. It is not clear if CF S. aureus strains are more virulent than strains isolated from non-CF patients. METHODOLOGY: Biofilm production was detected by a modified tissue culture plate method, presence of genes encoding for Panton-Valentine leukocidin (PVL) was investigated by a signal amplified sandwich hybridization assay and antimicrobial susceptibility patterns were detected by disk diffusion method. RESULTS: Staphylococcus aureus clinical isolates (n = 88) recovered from respiratory tract specimens in which 31 of them were from cystic fibrosis (CF) patients were analysed. Biofilm production was detected in 96.8% of CF isolates in which 32.3% exhibited strong positive phenotype and in 47.4% of non-CF isolates in which strong positive phenotype was not observed (p <0.05). All CF isolates were methicillin susceptible, whereas 53.4% of non-CF isolates (n = 31) were methicillin resistant. No resistance was observed for vancomycin, chloramphenicol and trimethoprim/sulfamethoxazole in any of the isolates. PVL genes were detected only in two isolates (2.3%), one from each group, CF and non-CF, which both were methicillin susceptible. CONCLUSION: Biofilm rather than PVL production appears to be an important virulence factor in CF patients. PMID- 24240051 TI - Battle against poliovirus in Pakistan. AB - On 22 Feb 2013, the Polio Monitoring Cell of Pakistan announced that the 2012 2013 polio campaign ended, and that 1.6 million children could not be vaccinated due to security concerns in several regions where polio workers had been killed. Those who could not be vaccinated included 50,000 children from the Federally Administrated Tribal Area (FATA), 150,000 form Khyber Pakhtoon Khao, 400,000 from a Quetta, 400,000 from Karachi, and a small number from the Rawalpindi District. These statistics are worrying, as several districts in the large metropolitan cities of Karachi and Quetta were also excluded. The fear of advanced medicine, ideas, or complex devices is a new phenomenon in many conservative and poor countries such as Pakistan, Afghanistan, Sudan, and Somalia. To safeguard the safety of the rest of the world, the failure in the implementation of WHO guidelines for vaccination must be regulated by the UN. There are a number of reasons for the phobias surrounding vaccination, but as technology continues to evolve at such a rapid rate, those with self-determined ideologies cannot cope with such advances. They become vocal to gain popularity and prevent the use of these technologies and medicine by creating and spreading rumors and propaganda of expediency. The struggle to vaccinate children is not easily understood by anyone living in the developed world. The irrational fear of vaccines and the lack of vaccination pose a serious global health risk and must be curbed through a wide variety of pro-vaccination media and religious campaigns. PMID- 24240050 TI - High prevalence of noroviruses among hospitalized diarrheal patients in Bangladesh, 2011. AB - INTRODUCTION: Norovirus is not usually investigated in diarrheal patients in Bangladesh which may account for the many cases where no pathogens are identified. METHODOLOGY: Stool specimens collected from diarrheal patients from three hospitals in Bangladesh during 2011 were investigated for norovirus RNA using real-time RT-PCR assay with norovirus type specific primers and probes. RESULTS: Of the 257 stool specimens tested, 28.4 % were norovirus positive. GII (71.2%) was the predominant strain followed by GI (20.5%), GI+GII (6.8%) and GIV (1.4%). Half of the norovirus positive stools (n=37) were co-infected with other pathogens. CONCLUSION: Continued surveillance of norovirus together with other viral and bacterial pathogens in hospitalized gastroenteritis patients as well as in the community will further elucidate the role and burden of different pathogens in diarrheal diseases. PMID- 24240052 TI - Mediterranean diet and hepatocellular carcinoma. AB - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial. METHODS: We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding factors, including chronic infection with hepatitis B/C viruses. RESULTS: Compared to MDS of 0-3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41-1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34 0.75) for MDS ? 5, with a significant trend (p<0.001). The detrimental effect of poor adherence to Mediterranean diet on HCC risk was disproportionally high among those chronically infected with hepatitis B and/or C viruses, with a suggestion of super-additive interaction, albeit statistically non-significant. CONCLUSIONS: Closer adherence to the Mediterranean diet appears to be protective against HCC. Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses. PMID- 24240053 TI - Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis. AB - BACKGROUND & AIMS: Improving health related quality of life (HrQoL) in patients with chronic diseases such as autoimmune hepatitis (AIH) should be a major treatment goal. However, little is known on the HrQoL in patients with AIH, and the topic is not given attention in current practice guidelines. We therefore conducted a single center study evaluating HrQoL in 103 consecutive outpatients with AIH. METHODS: Patient-reported HrQoL data were analysed in relation to clinical disease parameters and compared to representative data of the German population as well as control patients. RESULTS: Based on patient-reported data, a major depressive syndrome (10.8%) was found to be five times more frequent in AIH patients compared to the general population (p<0.001). The rate of severe symptoms of anxiety was also found to be significantly increased compared to the general population (p=0.006). In seven of the eleven patients who scored for a major depressive syndrome a psychiatric comorbidity had not been diagnosed before. Major factors associated with depression and anxiety were concerns with regard to the progression of the liver disease. CONCLUSIONS: This study identified--for the first time--a high rate of previously unrecognized severe symptoms of depression and anxiety in patients with AIH. Of importance for daily clinical practice, the factors associated with these symptoms may in part be amenable to targeted counselling and adequate treatment of the disease, thereby offering the chance to improve the care and HrQoL of AIH-patients. PMID- 24240054 TI - The human oncogene SCL/TAL1 interrupting locus is required for mammalian dopaminergic cell proliferation through the Sonic hedgehog pathway. AB - The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in all vertebrate species. In humans, the expression of Stil regulates cancer cell proliferation and survival. In this study, we examined the function of Stil in neural progenitor cell proliferation and neural differentiation using the mammalian dopaminergic (DA) PC12 cells. Stil is expressed in both proliferating and differentiated PC12 cells. The RNAi-mediated knockdown of Stil expression yielded a decreased proliferation rate of PC12 cells, whereas the overexpression of Stil transcript increased PC12 cell proliferation. The up- and down-regulation of the Sonic hedgehog (Shh) pathway by pharmacological approaches targeting Smoothened (Smo) demonstrated that Stil functions in the Shh pathway for PC12 proliferation. Smo antagonist cyclopamine decreased the proliferation rate of PC12 cells, whereas the overexpression of Stil rescued the cyclopamine-induced decrease in cell proliferation. Oppositely, the application of Smo agonist purmorphamine increased the rate of PC12 cell proliferation. However, the proliferation defect caused by Stil knockdown remained evident after activating the Shh pathway by purmorphamine. The expression of Stil is not required for PC12 cell neural differentiation. In PC12 cells transfected with Stil shRNA plasmids, the outgrowth of neurites persisted after treatment with nerve growth factor (NGF), whereas overexpression of Stil did not increase neurite growth in response to NGF induction. Together, the results from this study suggest a novel role for the oncogene Stil in neural progenitor cells through the Shh pathway, and further introduces Stil as a bio-marker for DA cells. PMID- 24240057 TI - Combinatorial function of velvet and AreA in transcriptional regulation of nitrate utilization and secondary metabolism. AB - Velvet is a conserved protein complex that functions as a regulator of fungal development and secondary metabolism. In the soil-inhabiting pathogen Fusarium oxysporum, velvet governs mycotoxin production and virulence on plant and mammalian hosts. Here we report a previously unrecognized role of the velvet complex in regulation of nitrate metabolism. F. oxysporum mutants lacking VeA or LaeA, two key components of the complex, were impaired in growth on the non preferred nitrogen sources nitrate and nitrite. Both velvet and the general nitrogen response GATA factor AreA were required for transcriptional activation of nitrate (nit1) and nitrite (nii1) reductase genes under de-repressing conditions, as well as for the nitrate-triggered increase in chromatin accessibility at the nit1 locus. AreA also contributed to chromatin accessibility and expression of two velvet-regulated gene clusters, encoding biosynthesis of the mycotoxin beauvericin and of the siderophore ferricrocin. Thus, velvet and AreA coordinately orchestrate primary and secondary metabolism as well as virulence functions in F. oxysporum. PMID- 24240055 TI - The toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCgamma2 signalling cascade. AB - The specific TLR2/1 complex activator Pam3CSK4 has been shown to provoke prominent activation and aggregation of human non-nucleated platelets. As Pam3CSK4-evoked platelet activation does not employ the major signalling pathway established in nucleated immune cells, we investigated if the TLR2/1 complex on platelets may initiate signalling pathways known to be induced by physiological agonists such as collagen via GPVI or thrombin via PARs. We found that triggering TLR2/1 complex-signalling with Pam3CSK4, in common with that induced via GPVI, and in contrast to that provoked by PARs, involves tyrosine phosphorylation of the adaptor protein LAT as well as of PLCgamma2 in a src- and Syk-dependent manner. In this respect, we provide evidence that Pam3CSK4 does not cross activate GPVI. Further, by the use of platelets from a Glanzmann's thrombasthenia patient lacking beta(3), in contrast to findings in nucleated immune cells, we show that the initiation of platelet activation by Pam3CSK4 does not involve integrin beta(3) signalling; whereas the latter, subsequent to intermediate TXA2 synthesis and signalling, was found to be indispensable for proper dense granule secretion and full platelet aggregation. Together, our findings reveal that triggering the TLR2/1 complex with Pam3CSK4 initiates human platelet activation by engaging tyrosine kinases of the src family and Syk, the adaptor protein LAT, as well as the key mediator PLCgamma2. PMID- 24240056 TI - Sustained IRE1 and ATF6 signaling is important for survival of melanoma cells undergoing ER stress. AB - Apoptosis triggered by endoplasmic reticulum (ER) stress is associated with rapid attenuation of the IRE1alpha and ATF6 pathways but persistent activation of the PERK branch of the unfolded protein response (UPR) in cells. However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that the kinetics and durations of activation of the UPR pathways are deregulated in melanoma cells undergoing ER stress. We show here that the IRE1alpha and ATF6 pathways are sustained along with the PERK signaling in melanoma cells subjected to pharmacological ER stress, and that this is, at least in part, due to increased activation of the MEK/ERK pathway. In contrast to an initial increase followed by rapid reduction in activation of IRE1alpha and ATF6 signaling in control cells that were relatively sensitive to ER stress-induced apoptosis, activation of IRE1alpha and ATF6 by the pharmacological ER stress inducer tunicamycin (TM) or thapsigargin (TG) persisted in melanoma cells. On the other hand, the increase in PERK signaling lasted similarly in both types of cells. Sustained activation of IRE1alpha and ATF6 signaling played an important role in protecting melanoma cells from ER stress-induced apoptosis, as interruption of IRE1alpha or ATF6 rendered melanoma cells sensitive to apoptosis induced by TM or TG. Inhibition of MEK partially blocked IRE1alpha and ATF6 activation, suggesting that MEK/ERK signaling contributed to sustained activation of IRE1alpha and ATF6. Taken together, these results identify sustained activation of the IRE1alpha and ATF6 pathways of the UPR driven by the MEK/ERK pathway as an important protective mechanism against ER stress-induced apoptosis in melanoma cells. PMID- 24240058 TI - Comparative analysis of mitochondrial genomes from closely related Rhynchosporium species reveals extensive intron invasion. AB - We sequenced and annotated the complete mitochondrial (mt) genomes of four closely related Rhynchosporium species that diverged ~14,000-35,000years ago. During this time frame, three of the mt genomes expanded significantly due to an invasion of introns into three genes (cox1, cox2, and nad5). The enlarged mt genomes contained ~40% introns compared to 8.1% in uninvaded relatives. Many intron gains were accompanied by co-conversion of flanking exonic regions. The comparative analysis revealed a highly variable set of non-intronic, free standing ORFs of unknown function (uORFs). This is consistent with a rapidly evolving accessory compartment in the mt genome of these closely related species. Only one free-standing uORF was shared among all mt genomes analyzed. This uORF had a mutation rate similar to the core mt protein-encoding genes, suggesting conservation of function among the species. The nucleotide composition of the core protein-encoding genes significantly differed from those of introns and uORFs. The mt mutation rate was 77 times higher than the nuclear mutation rate, indicating that the phylogeny inferred from mt genes may better resolve the phylogenetic relationships among closely related Rhynchosporium species than phylogenies inferred from nuclear genes. PMID- 24240059 TI - Evidence of adaptive intergenerational sex ratio adjustment in contemporary human populations. AB - Using the abrupt decline in sex ratio at birth in China during and immediately after the 1959-1961 Great Leap Forward Famine in China as a natural experiment, this study conducts difference-in-differences analysis to test the hypothesis that changes in the sex ratio at birth of the maternal generation can produce adaptive changes in the sex ratio at birth of the offspring generation toward the opposite direction, which was derived from the developmental and evolutionary psychological literature on female reproductive strategy. The results show that, after controlling for sex-selective abortion, the decline in the sex ratio at birth in 1962-1964 caused a substantial increase in the sex ratio at birth among children whose mothers were born in 1963. Such finding suggests the presence of adaptive intergenerational sex ratio adjustment in humans. PMID- 24240060 TI - A multicentre postal survey investigating the contribution of illness perceptions, coping and optimism to quality of life and mood in adults with muscle disease. AB - OBJECTIVE: To replicate the finding that illness perceptions influence quality of life in adults with muscle disease and to explore the additional influence of coping and optimism on quality of life and mood. DESIGN: A postal survey including questionnaires recording quality of life, mood, illness perceptions, optimism, coping and functional impairment. SETTING: National Health Service muscle clinics in the United Kingdom. PARTICIPANTS: A convenience sample of adults with muscle disease. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Individualised Neuromuscular Quality of Life Questionnaire, Hospital Anxiety and Depression Scale. RESULTS: A total of 226 completed questionnaires were returned. Although functional impairment explained most of the variance in three out of eight quality of life domains, psychological factors explained greater amounts of variance (between 19% and 52% of variance) in all other quality of life domains and in both mood domains (between 45% and 48% of variance). Overall, illness perceptions explained much of the variance in quality of life and mood score (between 5% and 37% of variance), while coping (up to 8% of variance) and optimism (up to 15% of variance) explained smaller amounts of variance. CONCLUSION: The results confirm that illness perceptions are associated with quality of life in muscle disease and suggest that they also influence mood. The addition of optimism and coping variables into the analysis yielded small increases in the proportions of variance in quality of life and mood which were explained. These results have implications for the composition of future psychological interventions. PMID- 24240061 TI - Efficacy of microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle: a randomized placebo-controlled trial. AB - OBJECTIVE: To compare the effects of a combination of therapeutic exercise and ultrasound with or without additional microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: An outpatient rehabilitation clinic in a tertiary university hospital. SUBJECTS: Infants (n = 20) with congenital muscular torticollis involving the entire sternocleidomastoid muscle. INTERVENTIONS: Group 1 comprised 10 infants who received therapeutic exercise with ultrasound alone and Group 2 comprised 10 infants who received the same treatment with microcurrent therapy. MAIN MEASURES: Passive cervical rotational range of motion was measured at before treatment and one, two, three, and six months after initial treatment. Thickness, cross-sectional area, and red pixel intensity on colour histograms, which were all assessed before treatment and at three months after initial treatment. Additionally, the duration of treatment was measured. RESULTS: The mean passive cervical rotational range of motion measured at three months posttreatment was significantly greater in Group 2 (101.1 degrees ) than that in Group 1 (86.4 degrees ), and the thickness, cross sectional area, and red pixel intensity of the affected sternocleidomastoid muscle were all less in Group 2 (7.8 mm, 100.3 mm(2), and 126.1, respectively) than those in Group 1 (9.6 mm, 121.5 mm2, and 140.5, respectively). The mean duration of treatment was significantly shorter in Group 2 (2.6 months) than in Group 1 (6.3 months). CONCLUSIONS: Microcurrent therapy may increase the efficacy of therapeutic exercise with ultrasound for the treatment of congenital muscular torticollis involving the entire sternocleidomastoid muscle. PMID- 24240062 TI - Optimized selection of anti-tumor recombinant antibodies from phage libraries on intact cells. AB - Generation of human recombinant antibody libraries displayed on the surface of the filamentous phage and selection of specific antibodies against desirable targets allows production of fully human antibodies usable for repeated administration in humans. Various lymphoid tissues from immunized donors, such as lymph nodes or peripheral blood lymphocytes from individuals with tumor or lymphocytes infiltrating tumor masses may serve as a source of specific anti tumor antibody repertoire for generation of tumor-focused phage display libraries. In the case of lack of tumor-associated antigens in the purified form, high affinity anti-tumor antibodies can be isolated through library panning on whole cells expressing these antigens. However, affinity selection against cell surface specific antigens within highly heterogeneous population of molecules is not a very efficient process that often results in the selection of unspecific antibodies or antibodies against intracellular antigens that are generally useless for targeted immunotherapy. In this work, we developed a new cell-based antibody selection protocol that, by eliminating the contamination of dead cells from the cell suspension, dramatically improves the selection frequency of anti tumor antibodies recognizing cell surface antigens. PMID- 24240063 TI - Influence of diet and sample collection time on 77 laboratory tests on healthy adults. AB - OBJECTIVES: We studied the effect of a standardized breakfast or lunch before blood sampling on 77 analytes. DESIGN AND METHODS: The mean difference between assays from 20 healthy adults was calculated on blood samples taken before and after food intake. Significant differences were tested using two-tailed Student t test and compared to the acceptable limits derived from analytical and intraindividual biological variation. RESULTS: Most of the analytes investigated were not significantly affected by food intake. Six of them were influenced by breakfast or lunch: triglycerides, glucose, creatinine, C-peptide and insulin were significantly upregulated, whereas testosterone was downregulated. Fourteen parameters were more influenced by time of sampling than by meals: nine decreased during the day (total bilirubin, BNP, myoglobin, cortisol, TSH, C-telopeptide, prolactin, ACTH, uric acid) and two increased (white blood cells, neutrophils). Three parameters showed levels that were similar at 9:00 am and 5:00 pm but their lowest level at 12:30 pm (inorganic phosphorus, osteocalcin, PTH). CONCLUSIONS: Fasting is necessary for some laboratory tests. Clinicians should be aware of variations due to sampling time before ordering non-fasting tests, and in the subsequent interpretation of results. PMID- 24240065 TI - "Notice of Violation of IEEE Publication Principles" Multiobjective Reinforcement Learning: A Comprehensive Overview. AB - Reinforcement learning is a powerful mechanism for enabling agents to learn in an unknown environment, and most reinforcement learning algorithms aim to maximize some numerical value, which represents only one long-term objective. However, multiple long-term objectives are exhibited in many real-world decision and control problems; therefore, recently, there has been growing interest in solving multiobjective reinforcement learning (MORL) problems with multiple conflicting objectives. The aim of this paper is to present a comprehensive overview of MORL. In this paper, the basic architecture, research topics, and naive solutions of MORL are introduced at first. Then, several representative MORL approaches and some important directions of recent research are reviewed. The relationships between MORL and other related research are also discussed, which include multiobjective optimization, hierarchical reinforcement learning, and multi-agent reinforcement learning. Finally, research challenges and open problems of MORL techniques are highlighted. PMID- 24240064 TI - Blood collection tube-related alterations in analyte concentrations in quality control material and serum specimens. AB - OBJECTIVES: Several previous studies have described the effects of interfering substances on clinical assay results; however, the effects of exogenous substances, particularly additives from blood collection tubes on quality control (QC) specimens and serum specimens have not been well examined. This study examines the effects of blood-collection tube additives on total triiodothyronine (TT3), and thyroxine (TT4), cortisol, and routine clinical chemistry tests in QC and serum specimens from apparently healthy volunteers. METHODS: QC and serum specimens were poured or collected into different blood collection tubes. TT3 and TT4, cortisol, and routine chemistry tests were analyzed from the different blood collection tube types. RESULTS: The findings of this study demonstrate statistically and/or clinically significant blood collection tube-related alterations in the TT3, TT4, and cortisol concentrations of QC specimens and TT4 concentrations from serum specimens. CONCLUSIONS: These findings have important implications for clinical laboratories, demonstrating that QC specimens should ideally, like patients' specimens, be poured into blood collection tubes. This strategy would reveal any adverse effects caused by blood collection tubes, which otherwise would not likely be detected by most routine QC practices. The results of this study also show the importance of producing blood collection tubes that contain additives that are truly inert and do not adversely affect clinical laboratory testing. PMID- 24240066 TI - Relationship between the effect of eldecalcitol and serum 25(OH)D level. AB - In previous studies, we demonstrated that 12-month treatment with 0.75MUg/day eldecalcitol increased bone mineral density in osteoporotic patients regardless of serum 25-hydroxyvitamin D (25(OH)D) level, and in a 3-year randomized double blind clinical trial, eldecalcitol significantly reduced the incidences of vertebral and wrist fractures compared to alfacalcidol. However, it remains unclear whether the fracture risk reduction by eldecalcitol is affected by serum 25(OH)D. In the fracture prevention trial, patients with low 25(OH)D level at baseline were supplemented with 400IU/day native vitamin D3. In the current study, patients from that trial were divided according to the tertiles of serum 25(OH)D level at 6 months after treatment initiation. The increases in lumbar and hip BMD by eldecalcitol were significantly higher in all tertiles than those by alfacalcidol. The incidences of vertebral and osteoporotic fractures tended to be lower in each tertile of the eldecalcitol-treated group than in the corresponding tertile of the alfacalcidol-treated group, with the exception of vertebral fractures in the low tertile. We also investigated whether eldecalcitol treatment affected levels of serum 25(OH)D, serum 1,25(OH)2D, and parathyroid hormone in patients without vitamin D supplementation. With eldecalcitol treatment, serum 1,25(OH)2D concentration was reduced by approximately 50%, whereas serum levels of parathyroid hormone and 25(OH)D were not affected. The major findings of the present study were that eldecalcitol did not affect serum 25(OH)D levels, and that it reduced the incidence of osteoporotic fractures and increased BMD in comparison with alfacalcidol regardless of serum 25(OH)D level within the range of serum 25(OH)D concentrations at or higher than 20ng/mL. Whether eldecalcitol is similarly effective at vitamin D deficient serum 25(OH)D levels remains to be clarified. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID- 24240067 TI - Variability in free 25(OH) vitamin D levels in clinical populations. AB - Our goal was to determine total and directly measured free 25-hydroxy vitamin D (25(OH)D) serum levels in humans with a range of 25(OH)D levels and clinical conditions associated with low and high vitamin D binding protein levels. Serum samples and clinical data were collected from 106 subjects: 62 without cirrhosis or pregnancy, 24 cirrhotic patients with albumin <2.9g/dL, and 20 pregnant women. Total 25(OH)D (LC/MS/MS) and "free" 25(OH)D (immunoassay) were measured. Total 25(OH)D was significantly lower in liver disease patients but free 25(OH)D concentrations were significantly higher in this group (p<.001). Neither total nor free 25(OH)D concentrations were significantly different in pregnant women vs. the comparator group. There were significant direct positive relationships between free 25(OH)D and total 25(OH)D concentrations for the entire dataset and for each group (p<.0001), however slopes of relationships differed in the cirrhotic group compared to pregnant women or the comparator group. In cirrhotics: y (free 25(OH)D)=2.52+0.29*X(total 25 (OH)D), r(2)=.51, p<.001; y=1.45+0.09*X; r(2)=.77, p<.0001 for pregnant women; and y=1.11+0.12*X; r(2)=.72, p<.0001 for the comparator group). CONCLUSIONS: directly measured free 25(OH)D serum concentrations and relationships between total and free 25(OH)D vary with clinical conditions, and may differ from those predicted by indirect estimation methods. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID- 24240068 TI - Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine. AB - Clinical trials of the human rotavirus vaccine RotarixTM (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota 037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration >=20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines. PMID- 24240069 TI - Wilkie's syndrome causing persistent vomiting post-colectomy. AB - INTRODUCTION: Wilkie's syndrome occurs when the superior mesenteric artery (SMA) compresses the third part of the duodenum causing proximal dilatation of small bowel. It is due to loss of the fat pad that sits between the duodenum and SMA and therefore is most commonly seen in people who have had significant weight loss. PRESENTATION OF CASE: A 79 year old man presented with anaemia and weight loss and an ascending colon malignancy was found. He was built up nutritionally and subsequently underwent a right hemicolectomy. Post operatively he had persistent nausea and vomiting and duodenal compression by the SMA was identified on CT imaging. He was managed initially with parenteral nutrition then gradually enteral feeding was introduced via a nasojejunal tube. Symptoms resolved with weight gain and he was discharged well. DISCUSSION: This condition often presents insidiously with intermittent nausea and vomiting. It infrequently occurs with a more acute onset in surgical patients. It has a classic appearance on CT imaging and is usually managed with conservative treatment although surgical options are feasible if this fails. CONCLUSION: Wilkie's syndrome is an interesting and infrequent cause of small bowel obstruction following colorectal surgery. A high index of suspicion is required. PMID- 24240070 TI - Isolated endometriosis causing sigmoid colon obstruction: A case report. AB - INTRODUCTION: Isolated endometriosis of the intestine causing large bowel obstruction is rare. PRESENTATION OF CASE: We present a case of endometriosis presenting as large bowel obstruction in a woman of childbearing age. She had no previous symptoms to suggest endometriosis and on presentation urgent surgery was required. The diagnosis of endometriosis was made only after pathological evaluation of the specimen. DISCUSSION: No cases of endometriosis confined to this sigmoid colon without pelvic involvement were noted in the literature. CONCLUSION: The diagnosis of endometriosis should be entertained when women of childbearing age presents with large bowel obstruction, whether or not the patient has other evidence of the disease. PMID- 24240071 TI - Mixed large cell neuroendocrine carcinoma with squamous cell carcinoma of the rectum: Report of a rare case and review of the literature. AB - INTRODUCTION: Mixed large cell neuroendocrine neoplasms of the rectum are rare and aggressive neoplasms. Survival is poor due to the high rate of lymph node metastases and distant metastases at the time of diagnosis. PRESENTATION OF CASE: We report a case of a 50-year-old male patient with a mixed large cell neuroendocrine carcinoma with squamous cell carcinoma of the rectum located 8cm from the anal verge, treated with low anterior resection and total mesorectal excision with free surgical margins. There were lymph nodes metastases but no distant metastases at the time of diagnosis. The patient refused to receive adjuvant chemotherapy and died 6 months later due to liver failure as a result of multiple hepatic metastases. DISCUSSION: There are not known predisposing factors for the development of neuroendocrine rectal carcinoma. A neuroendocrine carcinoma of the rectum is a rare tumor with an incidence of less than 0.1% of all colorectal malignancies. The median survival ranges from 5 to 10.4 months in several studies and there are not sufficient data in bibliography about ideal adjuvant therapy after resection of mixed squamous large cell neuroendocrine carcinoma of the rectum. CONCLUSION: Low anterior resection and total mesorectal excision with free surgical margins in the presence of lymph nodes metastasis is not a sufficient treatment for rectal neuroendocrine carcinoma. More studies should be done in order to determine the ideal adjuvant treatment of these rare and aggressive tumors. PMID- 24240072 TI - Bilateral spontaneous, simultaneous lower extremity hematomas in a patient on dalteparin. AB - INTRODUCTION: Bleeding related to low-molecular-weight heparins (LMWHs) is typically described as an excess of minor bleeding; however, several reports of spontaneous major bleeding have been noted. PRESENTATION OF CASE: A 58-year-old female presented to the hospital with bilateral spontaneous lower extremity hematomas which rapidly enlarged. CT studies demonstrated active arterial extravasation from small vessels at multiple sites within each leg with no dominant feeding artery identified on either side. She required multiple transfusions, administration of protamine, fresh frozen plasma (FFP), recombinant activated Factor VII and eventual surgery. DISCUSSION: Dalteparin provides an effective and economical method of anticoagulation, however there is a risk of significant, spontaneous arterial hemorrhage even in the absence of risk factors. CONCLUSION: Dalteparin can cause major spontaneous bleeding from multiple arterial sources. PMID- 24240073 TI - A retained plastic protective cover mimicking malignancy: Case report. AB - INTRODUCTION: Cases of retained foreign bodies during surgery are more frequently seen in developing countries. Following surgical procedures, unintentionally retained foreign bodies can cause serious complications, in addition to medico legal issues. PRESENTATION OF CASE: A 60-year-old man presented with abdominal cramps. He had previously undergone a laparoscopic radical right nephrectomy due to renal cell carcinoma. Abdominal tomography revealed a mass surrounding the main vascular structures with malignant features in the location of previously performed nephrectomy. Further evaluation of the mass was undertaken by PET/CT. Increased FDG uptake on the PET/CT scan suggested disease recurrence. Retroperitoneal lymph node dissection was performed. The dissection specimen was opened to determine the nature of the mass. Retained plastic foreign bodies were found. There were no malignant cells in the histopathological examination of the surgical specimen. DISCUSSION: A granulomatous reaction which is mainly responsible for morbidity occurs around the foreign bodies due to the inflammatory response. These granulomas may cause confusion during patient follow up, especially in those who have undergone major abdominal surgery due to cancer. CONCLUSION: Following surgical resection for malignancy, unintentionally retained foreign bodies can produce a moderate increase in FDG uptake mimicking disease recurrence. PMID- 24240074 TI - Reconstructive surgery in anal giant condyloma: Report of two cases. AB - INTRODUCTION: Giant anal condyloma also called Buschke-Lowenstein tumor is a rare sexually transmitted disease involving anogenital region with potential malignant degeneration into invasive squamous carcinoma. Complete surgical excision is the treatment of choice and often wide wounds are necessary to reach clear margins and prevent recurrence. PRESENTATION OF CASE: The authors present two cases treated with an S-plasty rotating and a bilateral house advancement flap respectively with good functional result. DISCUSSION: Giant anal condyloma also called Buschke-Lowenstein tumor is a large exophytic, cauliflower-like mass that is characterized by local aggressive behavior. Immunosuppression favors rapid growth of the condylomas and increases the risk of their malignant transformation. In limited lesions primary excision can be safely performed leaving wounds open to granulate while in more extensive lesions flap or skin graft coverage is preferable to decrease the length of recovery and minimize risk of severe anal stricture. Abdominoperineal resection should be performed for more extensive lesions with deep invasion, malignant transformation or tumor recurrence. CONCLUSION: Giant anal condyloma also called Buschke-Lowenstein is a rare pathology with mainly sporadic single center experience reported in literature. Surgical complete excision remains the best treatment although elevate should be eventual recurrence. No sufficient data are available to recommend any medical treatment such as interferon, radiotherapy or chemotherapy. PMID- 24240075 TI - A plain abdominal radiograph diagnosis of appendicitis. AB - INTRODUCTION: Despite reported poor sensitivity and specificity, plain abdominal radiographs have a role in the investigation of suspected appendicitis. PRESENTATION OF CASE: We report a case of a previously healthy 47 year old man, who presented with sudden onset abdominal pain associated with a raised temperature. He gave a short history of pain around the umbilicus, which radiated to his right iliac fossa over a period of hours. On examination his abdomen was soft with rebound tenderness in the right iliac fossa. Investigations revealed white cell count 11.2*109/L, CRP 4mg/L and normal haemoglobin, renal and liver function tests. An inflamed appendix was visible with thickened walls on a plain abdominal radiograph and was confirmed during laparoscopic appendectomy and subsequent histology. He made good recovery and was discharged. DISCUSSION: Prominent appendiceal wall and air in the appendix has been described in the literature as a CT finding that can distinguish appendicitis from other differential diagnoses and here we present a case of diagnosis of appendicitis on a plain abdominal radiograph showing this sign which to the best of our knowledge is rarely seen on abdominal films. CONCLUSION: Careful assessment of plain abdominal films in suspected appendicitis is encouraged not just for exclusion of other causes of pain but also in the possible detection of an inflamed appendix. PMID- 24240076 TI - Regeneration of ring-shaped lateral meniscus after partial resection of discoid meniscus with anterior cruciate ligament reconstruction. AB - INTRODUCTION: The ring-shaped lateral meniscus is very rare. Although it is essentially known as a congenital anomaly, a central tear in an incomplete discoid meniscus or an old bucket-handle tear in a meniscus may be easily mistaken for a ring-shaped meniscus. We experienced a ring-shaped lateral meniscus that regenerated after partial resection of a discoid meniscus together with anterior cruciate ligament (ACL) reconstruction. PRESENTATION OF CASE: A 37 year-old female patient still experienced unrelenting knee pain 6 months after ACL reconstruction and partial meniscectomy of a discoid lateral meniscus. A repeat arthroscopy was performed. The lateral tibial plateau was covered in the form of a ring by meniscus-like tissue. The meniscus-like tissue appeared to have regenerated inward toward the center from the stump after the partial meniscectomy and was connected from the anterior to posterior horn, forming an interhorn bridge. Partial meniscectomy was repeated. Histologically, the regenerated tissue was not meniscal, but comprised mature fibrocartilage; macroscopically; however, it was very similar to meniscal tissue. Two years after the initial operation, the patient had no complaints and experienced full return of function. DISCUSSION: The reason for such regeneration is unknown, but may have been attributed to the specific intra-articular environment that developed after the ACL reconstruction. CONCLUSION: This is the first report of regenerative development of a ring-shaped lateral meniscus. When a ring-shaped lateral meniscus is diagnosed, we must accurately determine whether it is a true congenital anomaly in consideration of the present case. PMID- 24240077 TI - Unusual presentation of 'numb chin syndrome' as the manifestation of metastatic adenocarcinoma of the lung. AB - INTRODUCTION: Numb chin syndrome (NCS) is the presence of hypoaesthesia or paraethesia of the lip and chin over the distribution of the mental nerve. It is often caused by the presence of a metastatic tumour in the mandible or the base of skull and represents advanced malignancy. PRESENTATION OF CASE: This paper presents an unusual case of NCS associated with metastatic adenocarcinoma of the lung, for which no obvious lesion was found in the mandible or base of the skull. DISCUSSION: NCS can oftentimes present itself in the absence of mandibular or base of skull metastatic lesions. CONCLUSION: NCS can be a sign of underlying advanced metastatic malignancy and therefore cannot be ignored and must be investigated fully. PMID- 24240078 TI - Reconstruction of short bowel syndrome after internal hernia in a pregnant woman with previous bariatric surgery. AB - INTRODUCTION: Bariatric surgery is most often performed with the laparoscopic Roux-en-Y gastric bypass. A complication to the laparoscopic Roux-en-Y gastric bypass is internal hernia, which occurs in up to 16% of the patients. Since the laparoscopic Roux-en-Y gastric bypass is performed in women of fertile age, internal hernia may occur during pregnancy. PRESENTATION OF CASE: A 22-year old woman with a history of laparoscopic Roux-en-Y gastric bypass suffered from massive internal hernia during pregnancy with widespread bowel necrosis. Extensive surgery was performed leaving the patient with an intact duodenum, 15cm of jejunum, 35cm of ileum and colon. Parenteral nutrition was initiated and ten months after the internal hernia, intestinal continuity was re-established. Ten weeks later the patient reached parenteral nutrition independence. DISCUSSION: Internal hernia after laparoscopic Roux-en-Y gastric bypass can be difficult to diagnose, especially during pregnancy and might be severe and life threatening for both mother and child. CONCLUSION: Obstetricians and abdominal surgeons must be aware of this condition. Surgery should be performed on a wide indication. When bowel necrosis is found it should be resected and in case of extensive bowel resection the patient should be evaluated in centres specialized in intestinal failure. PMID- 24240079 TI - Duodenal fistula associated with a peri-appendiceal abscess: A case report. AB - INTRODUCTION: Retroperitoneal abscess is an unusual presentation of perforated appendicitis. A fistula between the duodenum and an abscess resulting from appendicitis has not been previously reported. PRESENTATION OF CASE: A 53-year old Japanese man with a past medical history of hypertension and iron deficiency anemia presented with a 10-day history of fever and right lower abdominal pain, and was diagnosed with a retroperitoneal abscess secondary to perforated appendicitis. He was then treated with piperacillin and tazobactam after undergoing ultrasound-guided drainage, after which his overall condition improved. Due to iron deficiency anemia, we performed further evaluation for gastrointestinal bleeding and esophagogastroduodenoscopy showed an elevated lesion with granulomatous tissue in the duodenum, without an associated ulcer. At 10 days after abscess drainage, duodenography with contrast showed continuity between the abscess cavity and the duodenum. At 74 days after drainage, we performed laparoscopic appendectomy. Pathological examination showed granulomatous tissue inside the appendix with an inflammatory background and fecaliths infiltrated by macrophages. DISCUSSION: Perforated appendicitis has various presentations and many unusual fistulae have been reported, however, a fistula between a peri-appendiceal abscess and the duodenum has not yet been reported. A retroperitoneal abscess around the duodenum and appendix should be checked to differentiate it from Valentino's syndrome. CONCLUSION: We present the rare complication of a duodenal fistula during the treatment of perforated appendicitis. The possibility of fistula formation should be considered in patients with complicated appendicitis. PMID- 24240080 TI - Pyogenic discitis due to Abiotrophia adiacens. AB - INTRODUCTION: Abiotrophia species have been referred to as nutritionally variant streptococci because of their fastidious nutritional requirements for growth. Abiotrophia species are difficult to identify with conventional solid culture. PRESENTATION OF CASE: A 48-year-old woman was admitted to our hospital with severe low back pain and body temperature of 38.2 degrees C. Magnetic resonance imaging revealed edema and contrast enhancement of the L4 and L5 vertebral bodies with high signal intensity in the L3-4 and L4-5 intervertebral discs on the T2 weighted images. The patient underwent needle biopsy of the L3-4 disk. Cultures of disk biopsy samples and blood yielded gram positive cocci in short chains with scanty growth on chocolate agar. Further subculture with supplemented medium and subsequent 16S ribosomal RNA gene sequencing identified the pathogen as Abiotrhophia adiacens. The patient was treated with intravenous ampicillin. At 6 month follow-up, the patient was free of symptoms. DISCUSSION: Causative microorganisms remain unidentified in 25-40% of spinal infection cases. Abiotrophia species grow poorly on conventional solid media, and require pyridoxal or thiol group supplementation. Use of Brucella HK agar or GAM agar plate is helpful for detection of Abiotrophia species. We first confirmed the diagnosis by direct identification of Abiotrophia adiacens from infected disk. Abiotrophia species are one of the major pathogens of infective endocarditis accounting for 5% of cases. Considering their fastidious nature, it is likely that most cases of Abiotrophia discitis are falsely classified as culture negative discitis; therefore, their role in pyogenic discitis may be underestimated. CONCLUSION: Subculture using nutritionally supplemented media is crucial for their identification. PMID- 24240081 TI - Duodenal ulcer penetration into the liver at the previous left hemihepatectomy site. AB - INTRODUCTION: Duodenal ulcer penetration into the liver is a rare, but serious complication. Its frequency was thought to have decreased owing to advances in therapies for peptic ulcers. However, we encountered a case in which the duodenal ulcer had penetrated into a previous hemihepatectomy site. PRESENTATION OF CASE: A 69-year-old man with a history of left hemihepatectomy 20 months previously presented to the emergency room with sudden-onset abdominal pain and nausea. An upper gastrointestinal examination with a fiberscope revealed a giant ulcer in the duodenal bulb. In addition, a foreign body was detected at the ulcer floor and was strongly suspected of being a ligature from previous hemihepatectomy. DISCUSSION: The presence of a gas-filled liver mass and bowel wall thickening with inflammatory changes are important imaging findings for prompt diagnosis of such a condition, but in this case, none of these were reported. Further, no definite abscess was found. Thus, the patient was treated conservatively with a proton pump inhibitor. CONCLUSION: This case demonstrates the importance of using absorbable suture materials, adequate lavage in the postoperative peritoneal space and gastroduodenal mucosal protection postoperatively. PMID- 24240082 TI - A very late recurrence of a formerly misdiagnosed low grade endometrial stromal sarcoma metastasized to the colon. AB - INTRODUCTION: Endometrial stromal sarcomas are rare mesenchymal neoplasms of the uterus with an indolent clinical course but a high risk of recurrence. PRESENTATION OF CASE: We report a case of a 78 year old woman who presented with rectal bleeding and recurrent urinary tract infections, caused by a very late recurrence of a formerly misdiagnosed low grade endometrial stromal sarcoma, metastasized to the colon. DISCUSSION: Endometrial stromal sarcomas are difficult to diagnose, both due to the rarity of the tumor and because of the close resemblance of the tumor to normal stromal tissue. These tumors are known for a high tendency of recurrence, therefore long term follow up is required in patients with endometrial stromal sarcoma. CONCLUSION: In patients with a history known for endometrial stromal sarcoma recurrence should always be considered. PMID- 24240083 TI - Laparoscopic pancreaticoduodenectomy after endovascular repair for abdominal aortic aneurysm. AB - INTRODUCTION: Most gastroenterological surgeries, even pancreatic surgery, can now be performed laparoscopically. However, the management of concomitant abdominal aortic aneurysm (AAA) and intra-abdominal malignancy is controversial. The performance of endovascular repair (EVAR) for AAA has been increasing; however, there is no report of laparoscopic pancreaticoduodenectomy after EVAR. PRESENTATION OF CASE: A pancreatic tumor was detected during follow-up after EVAR for AAA. The enlarging tumor was diagnosed as an intraductal papillary mucinous tumor with a nodule. Laparoscopic pancreaticoduodenectomy was safely performed. After laparoscopic dissection around the pancreas head, an additional incision was made in the upper abdomen, and pancreatic reconstruction was performed through the incision. In spite of grade B pancreatic fistulae, the patient recovered with medical therapy. The pathological diagnosis was intraductal papillary mucinous adenoma with small foci of carcinoma in situ. The patient has been well with neither recurrence of the tumor nor any cardiovascular events for 18 months. DISCUSSION: The management of concomitant malignancy and AAA is challenging, especially in patients with a pancreatic tumor. The reasons for the rarity of treatment include prognosis, anatomical vicinity, and postoperative complications. EVAR reduces retroperitoneal adhesions. A laparoscopic approach provides a small operative field and decreases mutual interference with AAA. Moreover, reconstruction is performed through an upper abdominal incision apart from the AAA. Hand-sewing provides more reliable stability of the anastomosis. CONCLUSION: The increasing frequency of performance of EVAR for AAA and subsequent computed tomography may help to detect malignancy. Laparoscopic surgery appears to be a valid approach to malignancy after EVAR. PMID- 24240084 TI - Acute ischemic gangrene of the rectum: Report of 3 cases and review of literature. AB - INTRODUCTION: Acute ischemia of the rectum resulting in full thickness necrosis is extremely uncommon because of its excellent blood supply. PRESENTATION OF CASE: We present 3 cases with spontaneous ischemic gangrene of the rectum. All three patients were elderly with atherosclerotic arterial disease and presented with hypotensive shock but in none of these patients we encountered a precipitating factor such as preceding vascular surgery or shock state. DISCUSSION: A high index of suspicion should be maintained in elderly patients with atherosclerotic disease who present with lower GI symptoms with hypotensive shock and an inflamed rectum on CT scan. Immediate beside proctoscopy should be offered to these patients and if the diagnosis is confirmed these patients should be taken to the operating room immediately. If the entire rectum is found to be gangrenous then an emergency APR should be performed and the perineal wound left open. If the rectum is partially gangrenous then a low anterior resection with Hartman's procedure for diversion is appropriate. CONCLUSION: Prompt diagnosis and resuscitation followed by immediate surgical intervention is necessary to save these elderly patients. PMID- 24240085 TI - ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer. AB - Labelled 5alpha-dihydrotestosterone (DHT) binding experiments have shown that expression levels of (yet unidentified) membrane androgen receptors (mAR) are elevated in prostate cancer and correlate with a negative prognosis. However, activation of these receptors which mediate a rapid androgen response can counteract several cancer hallmark functions such as unlimited proliferation, enhanced migration, adhesion and invasion and the inability to induce apoptosis. Here, we investigate the downstream signaling pathways of mAR and identify rapid DHT induced activation of store-operated Ca2+ entry (SOCE) in primary cultures of human prostate epithelial cells (hPEC) from non-tumorous tissue. Consequently, down-regulation of Orai1, the main molecular component of Ca2+ release-activated Ca2+ (CRAC) channels results in an almost complete loss of DHT induced SOCE. We demonstrate that this DHT induced Ca2+ influx via Orai1 is important for rapid androgen triggered prostate specific antigen (PSA) release. We furthermore identified alterations of the molecular components of CRAC channels in prostate cancer. Three lines of evidence indicate that prostate cancer cells down-regulate expression of the Orai1 homolog Orai3: First, Orai3 mRNA expression levels are significantly reduced in tumorous tissue when compared to non-tumorous tissue from prostate cancer patients. Second, mRNA expression levels of Orai3 are decreased in prostate cancer cell lines LNCaP and DU145 when compared to hPEC from healthy tissue. Third, the pharmacological profile of CRAC channels in prostate cancer cell lines and hPEC differ and siRNA based knock-down experiments indicate changed Orai3 levels are underlying the altered pharmacological profile. The cancer-specific composition and pharmacology of CRAC channels identifies CRAC channels as putative targets in prostate cancer therapy. PMID- 24240086 TI - Salivary adiponectin levels are associated with training intensity but not with bone mass or reproductive function in elite Rhythmic Gymnasts. AB - Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica. The aim of the present study was to evaluate the effect of training intensity on salivary adiponectin levels and assess a possible role of salivary adiponectin levels as a predictive factor of reproductive dysfunction and bone mass acquisition in elite RGs. The study included 80 elite female RGs participating in the World Rhythmic Gymnastics Championship tournament held in Montpellier, France on September 2011. Anthropometric values were assessed, training data and menstrual pattern were recorded, bone mass was measured with Broadband ultrasound attenuation (dB/Mhz) and baseline salivary adiponectin levels were determined. The athletes were classified as intensely and very intensely trained, considering the mean training intensity (40.84h/week). Moreover, considering their reproductive status, they were divided into RG's with normal menstruation, primary amenorrhea and oligomenorrhea. All comparisons were adjusted to age, BMI and body fat percentage differences. Very intensely trained RGs showed higher salivary adiponectin levels (p=0.05). Moreover, salivary adiponectin levels showed significant correlation with training intensity (r=0.409, p=0.003). On the other hand, no association of salivary adiponectin levels was documented with either reproductive function or bone mass acquisition. The results of the present study suggest that, in elite RGs, salivary adiponectin levels are associated with the intensity of training, possibly reflecting the deterioration of energy balance rather than the training stress. On the other hand, a predictive role of salivary adiponectin levels in reproductive dysfunction or bone mass acquisition could not be supported. PMID- 24240087 TI - What is the difference between OASIS and OPERA? Roughly five pixels: orthographic structure biases the perceived length of letter strings. AB - A thorough understanding of monosyllabic-word-recognition processes, in contrast with multisyllabic-word processing, has accumulated over the past decades. One fundamental challenge regarding multisyllabic words concerns their parsing into smaller units and the nature of the cues determining the parsing. We propose that the organization of consonant and vowel letters provides powerful cues for parsing, and we present data from a new task showing that a word's orthographic structure, as determined by the number of vowel-letter clusters, influences estimations of its length. Words were briefly presented on a computer screen, and participants had to estimate word length by drawing a line on the screen with the mouse. In three experiments, participants estimated words comprising fewer orthographic units as shorter than words comprising more units even though the words matched for number of letters. Further results demonstrated that the length bias was driven by orthographic information and not by phonological structure. PMID- 24240088 TI - Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice. AB - Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. PMID- 24240089 TI - Suppression of tumorigenesis in mitochondrial NADP(+)-dependent isocitrate dehydrogenase knock-out mice. AB - The tumor host microenvironment is increasingly viewed as an important contributor to tumor growth and suppression. Cellular oxidative stress resulting from high levels of reactive oxygen species (ROS) contributes to various processes involved in the development and progress of malignant tumors including carcinogenesis, aberrant growth, metastasis, and angiogenesis. In this regard, the stroma induces oxidative stress in adjacent tumor cells, and this in turn causes several changes in tumor cells including modulation of the redox status, inhibition of cell proliferation, and induction of apoptotic or necrotic cell death. Because the levels of ROS are determined by a balance between ROS generation and ROS detoxification, disruption of this system will result in increased or decreased ROS level. Recently, we demonstrated that the control of mitochondrial redox balance and cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) that supplies NADPH for antioxidant systems. To explore the interactions between tumor cells and the host, we evaluated tumorigenesis between IDH2-deficient (knock-out) and wild-type mice in which B16F10 melanoma cells had been implanted. Suppression of B16F10 cell tumorigenesis was reproducibly observed in the IDH2-deficient mice along with significant elevation of oxidative stress in both the tumor and the stroma. In addition, the expression of angiogenesis markers was significantly down-regulated in both the tumor and the stroma of the IDH2-deficient mice. These results support the hypothesis that redox status-associated changes in the host environment of tumor-bearing mice may contribute to cancer progression. PMID- 24240090 TI - Human diseases of the SSU processome. AB - Ribosomes are the cellular machines responsible for protein synthesis. Ribosome biogenesis, the production of ribosomes, is a complex process involving pre ribosomal RNA (rRNA) cleavages and modifications as well as ribosomal protein assembly around the rRNAs to create the functional ribosome. The small subunit (SSU) processome is a large ribonucleoprotein (RNP) in eukaryotes required for the assembly of the SSU of the ribosome as well as for the maturation of the 18S rRNA. Despite the fundamental nature of the SSU processome to the survival of any eukaryotic cell, mutations in SSU processome components have been implicated in human diseases. Three SSU processome components and their related human diseases will be explored in this review: hUTP4/Cirhin, implicated in North American Indian childhood cirrhosis (NAIC); UTP14, implicated in infertility, ovarian cancer, and scleroderma; and EMG1, implicated in Bowen-Conradi syndrome (BCS). Diseases with suggestive, though inconclusive, evidence for the involvement of the SSU processome in their pathogenesis are also discussed, including a novel putative ribosomopathy. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. PMID- 24240092 TI - Mercury specifically induces LINE-1 activity in a human neuroblastoma cell line. AB - L1 retro-elements comprise 17% of the human genome. Approximately 100 copies of these autonomous mobile elements are active in our DNA and can cause mutations, gene disruptions, and genomic instability. Therefore, human cells control the activities of L1 elements, in order to prevent their deleterious effects through different mechanisms. However, some toxic agents increase the retrotransposition activity of L1 elements in somatic cells. In order to identify specific effects of neurotoxic metals on L1 activity in neuronal cells, we studied the effects of mercury and cobalt on L1-retroelement activity by measuring levels of cellular transcription, protein expression, and genomic retrotransposition in a neuroblastoma cell line compared with the effects in three non-neuronal cell lines. Our results show that mercury increased the expression of L1 RNA, the activity of the L1 5'UTR, and L1 retrotransposition exclusively in the neuroblastoma cell line but not in non-neuronal cell lines. However, cobalt increased the expression of L1 RNA in neuroblastoma cells, HeLa cells, and wild type human fibroblasts, and also increased the activity of the L1 5'UTR as well as the SV40 promoter in HeLa cells but not in neuroblastoma cells. Exposure to cobalt did not result in increased retrotransposition activity in HeLa cells or neuroblastoma cells. We conclude that non-toxic levels of the neurotoxic agent mercury could influence DNA by increasing L1 activities, specifically in neuronal cells, and may make these cells susceptible to neurodegeneration over time. PMID- 24240091 TI - Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity. AB - Mitochondria manufacture and release metabolites and manage calcium during neuronal activity and synaptic transmission, but whether long term alterations in mitochondrial function contribute to the neuronal plasticity underlying changes in organism behavior patterns is still poorly understood. Although normal neuronal plasticity may determine learning, in contrast a persistent decline in synaptic strength or neuronal excitability may portend neurite retraction and eventual somatic death. Anti-death proteins such as Bcl-xL not only provide neuroprotection at the neuronal soma during cell death stimuli, but also appear to enhance neurotransmitter release and synaptic growth and development. It is proposed that Bcl-xL performs these functions through its ability to regulate mitochondrial release of bioenergetic metabolites and calcium, and through its ability to rapidly alter mitochondrial positioning and morphology. Bcl-xL also interacts with proteins that directly alter synaptic vesicle recycling. Bcl-xL translocates acutely to sub-cellular membranes during neuronal activity to achieve changes in synaptic efficacy. After stressful stimuli, pro-apoptotic cleaved delta N Bcl-xL (DeltaN Bcl-xL) induces mitochondrial ion channel activity leading to synaptic depression and this is regulated by caspase activation. During physiological states of decreased synaptic stimulation, loss of mitochondrial Bcl-xL and low level caspase activation occur prior to the onset of long term decline in synaptic efficacy. The degree to which Bcl-xL changes mitochondrial membrane permeability may control the direction of change in synaptic strength. The small molecule Bcl-xL inhibitor ABT-737 has been useful in defining the role of Bcl-xL in synaptic processes. Bcl-xL is crucial to the normal health of neurons and synapses and its malfunction may contribute to neurodegenerative disease. PMID- 24240093 TI - Prolonged insulin stimulation down-regulates GLUT4 through oxidative stress mediated retromer inhibition by a protein kinase CK2-dependent mechanism in 3T3 L1 adipocytes. AB - Although insulin acutely stimulates glucose uptake by promotion of GLUT4 translocation from intracellular compartments to the plasma membrane in adipocytes and muscles, long term insulin stimulation causes GLUT4 depletion that is particularly prominent in the insulin-responsive GLUT4 storage compartment. This effect is caused mainly by accelerated lysosomal degradation of GLUT4, although the mechanism is not fully defined. Here we show that insulin acutely induced dissociation of retromer components from the low density microsomal membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on the activity of protein kinase CK2 but not phosphatidylinositol 3-kinase or extracellular signal-regulated kinase 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif (Vps35-S7A) was resistant to insulin induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Furthermore, insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner. PMID- 24240094 TI - Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes. AB - Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID- 24240095 TI - Mechanism of hepatitis C virus (HCV)-induced osteopontin and its role in epithelial to mesenchymal transition of hepatocytes. AB - Osteopontin (OPN) is a secreted phosphoprotein, originally characterized in malignant-transformed epithelial cells. OPN is associated with tumor metastasis of several tumors and is overexpressed in hepatocellular carcinoma (HCC) tissue involving HCC invasion and metastasis. Importantly, OPN is significantly up regulated in liver injury, inflammation, and hepatitis C virus (HCV)-associated HCC. However, the underlying mechanisms of OPN activation and its role in HCV mediated liver disease pathogenesis are not known. In this study, we investigated the mechanism of OPN activation in HCV-infected cells. We demonstrate that HCV mediated Ca(2+) signaling, elevation of reactive oxygen species, and activation of cellular kinases such as p38 MAPK, JNK, PI3K, and MEK1/2 are involved in OPN activation. Incubation of HCV-infected cells with the inhibitors of AP-1 and Sp1 and site-directed mutagenesis of AP-1- and Sp1-binding sites on the OPN promoter suggest the critical role of AP-1 and Sp1 in OPN promoter activation. In addition, we show the in vivo interactions of AP-1 and Sp1 with the OPN promoter using chromatin immunoprecipitation assay. We also show the calpain-mediated processing of precursor OPN (~75 kDa) into ~55-, ~42-, and ~36-kDa forms of OPN in HCV-infected cells. Furthermore, we demonstrate the critical role of HCV induced OPN in increased phosphorylation of Akt and GSK-3beta followed by the activation of beta-catenin, which can lead to EMT of hepatocytes. Taken together, these studies provide an insight into the mechanisms of OPN activation that is relevant to the metastasis of HCV-associated HCC. PMID- 24240096 TI - Interaction of Bcl-2 with the autophagy-related GABAA receptor-associated protein (GABARAP): biophysical characterization and functional implications. AB - Apoptosis and autophagy are fundamental homeostatic processes in eukaryotic organisms fulfilling essential roles in development and adaptation. Recently, the anti-apoptotic factor Bcl-2 has been reported to also inhibit autophagy, thus establishing a potential link between these pathways, but the mechanistic details are only beginning to emerge. Here we show that Bcl-2 directly binds to the phagophore-associated protein GABARAP. NMR experiments revealed that the interaction critically depends on a three-residue segment (EWD) of Bcl-2 adjacent to the BH4 region, which is anchored to one of the two hydrophobic pockets on the GABARAP molecule. This is at variance with the majority of GABARAP interaction partners identified previously, which occupy both hydrophobic pockets simultaneously. Bcl-2 affinity could also be detected for GEC1, but not for other mammalian Atg8 homologs. Finally, we provide evidence that overexpression of Bcl 2 inhibits lipidation of GABARAP, a key step in autophagosome formation, possibly via competition with the lipid conjugation machinery. These results support the regulatory role of Bcl-2 in autophagy and define GABARAP as a novel interaction partner involved in this intricate connection. PMID- 24240097 TI - A chemoreceptor that detects molecular carbon dioxide. AB - Animals from diverse phyla possess neurons that are activated by the product of aerobic respiration, CO2. It has long been thought that such neurons primarily detect the CO2 metabolites protons and bicarbonate. We have determined the chemical tuning of isolated CO2 chemosensory BAG neurons of the nematode Caenorhabditis elegans. We show that BAG neurons are principally tuned to detect molecular CO2, although they can be activated by acid stimuli. One component of the BAG transduction pathway, the receptor-type guanylate cyclase GCY-9, suffices to confer cellular sensitivity to both molecular CO2 and acid, indicating that it is a bifunctional chemoreceptor. We speculate that in other animals, receptors similarly capable of detecting molecular CO2 might mediate effects of CO2 on neural circuits and behavior. PMID- 24240098 TI - Determinants in the beta and delta subunit cytoplasmic loop regulate Golgi trafficking and surface expression of the muscle acetylcholine receptor. AB - The molecular determinants that govern nicotinic acetylcholine receptor (AChR) assembly and trafficking are poorly defined, and those identified operate largely during initial receptor biogenesis in the endoplasmic reticulum. To identify determinants that regulate later trafficking steps, we performed an unbiased screen using chimeric proteins consisting of CD4 fused to the muscle AChR subunit cytoplasmic loops. In C2 mouse muscle cells, we found that CD4-beta and delta subunit loops were expressed at very low levels on the cell surface, whereas the other subunit loops were robustly expressed on the plasma membrane. The low surface expression of CD4-beta and delta loops was due to their pronounced retention in the Golgi apparatus and also to their rapid internalization from the plasma membrane. Both retention and recovery were mediated by the proximal 25-28 amino acids in each loop and were dependent on an ordered sequence of charged and hydrophobic residues. Indeed, betaK353L and deltaK351L mutations increased surface trafficking of the CD4-subunit loops by >6-fold and also decreased their internalization from the plasma membrane. Similarly, combined betaK353L and deltaK351L mutations increased the surface levels of assembled AChR expressed in HEK cells to 138% of wild-type levels. This was due to increased trafficking to the plasma membrane and not decreased AChR turnover. These findings identify novel Golgi retention signals in the beta and delta subunit loops that regulate surface trafficking of assembled AChR and may help prevent surface expression of unassembled subunits. Together, these results define molecular determinants that govern a Golgi-based regulatory step in nicotinic AChR trafficking. PMID- 24240100 TI - Prevention of cavus foot deformity following gradual distraction osteogenesis for first brachymetatarsia--technique tip. PMID- 24240099 TI - Neuroendocrine tumours of the head and neck: anatomical, functional and molecular imaging and contemporary management. AB - Neuroendocrine tumours (NETs) of the head and neck are rare neoplasms and can be of epithelial or non-epithelial differentiation. Although the natural history of NETs is variable, it is crucial to establish an early diagnosis of these tumours as they can be potentially curable. Conventional anatomical imaging and functional imaging using radionuclide scintigraphy and positron emission tomography/computed tomography can be complementary for the diagnosis, staging and monitoring of treatment response. This article describes and illustrates the imaging features of head and neck NETs, discusses the potential future role of novel positron-emitting tracers that are emerging into clinical practice and reviews contemporary management of these tumours. Familiarity with the choice of imaging techniques and the variety of imaging patterns and treatment options should help guide radiologists in the management of this rare but important subgroup of head and neck neoplasms. PMID- 24240102 TI - The uncertainty of mass discharge measurements using pumping methods under simplified conditions. AB - Mass discharge measurements at contaminated sites have been used to assist with site management decisions, and can be divided into two broad categories: point scale measurement techniques and pumping methods. Pumping methods can be sub divided based on the pumping procedures used into sequential, concurrent, and tandem circulating well categories. Recent work has investigated the uncertainty of point measurement methods, and to a lesser extent, pumping methods. However, the focus of this study was a direct comparison of uncertainty between the various pumping method approaches that have been used, as well as a comparison of uncertainty between pumping and point measurement methods. Mass discharge measurement error was investigated using a Monte Carlo modeling analysis as a function of the contaminant plume position and width, and as a function of the pumping conditions used in the different pumping tests. Results indicated that for the conditions investigated, uncertainty in mass discharge estimates based on pumping methods was 1.3 to 16 times less than point measurement method uncertainty, and that a sequential pumping approach resulted in 5 to 12 times less uncertainty than the concurrent pumping or tandem circulating well approaches. Uncertainty was also investigated as a function of the plume width relative to well spacing. For a given well spacing, uncertainty decreased for all methods as the plume width increased, and comparable levels of uncertainty between point measurement and pumping methods were obtained when three wells were distributed across the plume. A hybrid pumping technique in which alternate wells were pumped concurrently in two separate campaigns yielded similar uncertainty to the sequential pumping approach. This suggests that the hybrid approach can be used to capitalize on the advantages of sequential pumping yet minimize the overall test duration. PMID- 24240101 TI - A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling. AB - The biochemical regulatory network downstream of receptor tyrosine kinase (RTK) signaling is controlled by two opposing ETS family members: the transcriptional activator Pointed (Pnt) and the transcriptional repressor Yan. A bistable switch model has been invoked to explain how pathway activation can drive differentiation by shifting the system from a high-Yan/low-Pnt activity state to a low-Yan/high-Pnt activity state. Although the model explains yan and pnt loss of-function phenotypes in several different cell types, how Yan and Pointed protein expression dynamics contribute to these and other developmental transitions remains poorly understood. Toward this goal we have used a functional GFP-tagged Pnt transgene (Pnt-GFP) to perform a comparative study of Yan and Pnt protein expression throughout Drosophila development. Consistent with the prevailing model of the Pnt-Yan network, we found numerous instances where Pnt GFP and Yan adopt a mutually exclusive pattern of expression. However we also observed many examples of co-expression. While some co-expression occurred in cells where RTK signaling is presumed low, other co-expression occurred in cells with high RTK signaling. The instances of co-expressed Yan and Pnt-GFP in tissues with high RTK signaling cannot be explained by the current model, and thus they provide important contexts for future investigation of how context-specific differences in RTK signaling, network topology, or responsiveness to other signaling inputs, affect the transcriptional response. PMID- 24240103 TI - Influence of calcite on uranium(VI) reactive transport in the groundwater-river mixing zone. AB - Calcite is an important, relatively soluble mineral phase that can affect uranium reactive transport in subsurface sediments. This study was conducted to investigate the distribution of calcite and its influence on uranium adsorption and reactive transport in the groundwater-river mixing zone of the Hanford 300A site, Washington State. Simulations using a two-dimensional (2D) reactive transport model under field-relevant hydrological and hydrogeochemical conditions revealed the development of a calcite reaction front through the mixing zone as a result of dynamic groundwater-river interactions. The calcite concentration distribution, in turn, affected the concentrations of aqueous carbonate and calcium, and pH through dissolution, as river waters intruded and receded from the site at different velocities in response to stage changes. The composition variations in groundwater subsequently influenced uranium mobility and discharge rates into the river in a complex fashion. The results implied that calcite distribution and concentration are important variables that need to be quantified for accurate reactive transport predictions of uranium, especially in dynamic groundwater-river mixing zones. PMID- 24240104 TI - The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells. AB - Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. PMID- 24240105 TI - Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid. AB - Enantioselective oxidative stress and toxin release from Microcystis aeruginosa after exposure to the chiral herbicide diclofop acid were investigated. Racemic diclofop acid, R-diclofop acid and S-diclofop acid induced reactive oxygen species (ROS) generation, increased the concentration of malondialdehyde (MDA), enhanced the activity of superoxide dismutase (SOD) and triggered toxin release in M. aeruginosa to varying degrees. The increase in MDA concentration and SOD activity in M. aeruginosa occurred sooner after exposure to diclofop acid than when the cyanobacteria was exposed to either the R- and the S-enantiomer. In addition, enantioselective toxicity of the enantiomers was observed. The R enantiomer trigged more ROS generation, more SOD activity and more toxin synthesis and release in M. aeruginosa cells than the S-enantiomer. Diclofop acid and its R-enantiomer may collapse the transmembrane proton gradient and destroy the cell membrane through lipid peroxidation and free radical oxidation, whereas the S-enantiomer did not demonstrate such action. R-diclofop acid inhibits the growth of M. aeruginosa in the early stage, but ultimately induced greater toxin release, which has a deleterious effect on the water column. These results indicate that more comprehensive study is needed to determine the environmental safety of the enantiomers, and application of chiral pesticides requires more direct supervision and training. Additionally, lifecycle analysis of chiral pollutants in aquatic system needs more attention to aide in the environmental assessment of chiral pesticides. PMID- 24240106 TI - Differential apoptotic and proliferative activities of wild-type FOXL2 and blepharophimosis-ptosis-epicanthus inversus syndrome (BPES)-associated mutant FOXL2 proteins. AB - FOXL2 is an essential transcription factor that is required for proper development of the ovary and eyelid. Mutations in FOXL2 cause an autosomal dominant genetic disorder, blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). BPES type I patients have eyelid malformation and premature ovarian failure leading to infertility, whereas women with type II BPES are fertile or subfertile. In the present study, we evaluated and compared apoptotic and antiproliferative activities of wild-type (WT) and mutant FOXL2 proteins found in BPES type I and II in human granulosa cell tumor-derived KGN cells. Ectopic expression of WT FOXL2 induced apoptosis and inhibited cell cycle progression in human granulosa cells. In contrast, mutated FOXL2s found in BPES type I significantly reduced these activities, whereas mutated FOXL2s in BPES type II showed intermediate activities. Furthermore, mutant FOX L2 proteins were defective in activating transcription of target genes including Caspase 8, TNF R1, FAS, p21, and BMP4, which regulate apoptosis, proliferation, and differentiation of granulosa cells. Thus, decreased apoptotic and antiproliferative activities caused by mutant forms of FOXL2 found in BPES patients may at least partially contribute to the pathophysiology of ovarian dysfunction. PMID- 24240107 TI - Nanotubular MnO2/graphene oxide composites for the application of open air breathing cathode microbial fuel cells. AB - Nanotubular shaped alpha-MnO2/graphene oxide nanocomposites were synthesized via a simple, cost and time efficient hydrothermal method. The growth of hollow structured MnO2 nanotubes preferentially occurred along the [001] direction as evidenced from the morphological and structural characterizations. The tunnels of alpha-MnO2 nanotubes easily accommodated the molecular oxygen and exhibited excellent catalytic activity towards the oxygen reduction reaction over the rod structure and was further enhanced with the effective carbon support graphene oxide. The MnO2 nanotubes/graphene oxide nanocomposite modified electrode exhibited a maximum power density of 3359 mW m(-2) which is 7.8 fold higher than that of unmodified electrode and comparable with the Pt/C modified electrode. The microbial fuel cell equipped with MnO2 nanotubes/graphene oxide nanocomposite modified cathode exhibited quick start up and excellent durability over the studied electrodes and is attributed to the high surface area and number of active sites. These findings not only provide the fundamental studies on carbon supported low-dimensional transition-metal oxides but also open up the new possibilities of their applications in green energy devices. PMID- 24240108 TI - HDM2 regulation by AURKA promotes cell survival in gastric cancer. AB - PURPOSE: Suppression of P53 (tumor protein 53) transcriptional function mediates poor therapeutic response in patients with cancer. Aurora kinase A (AURKA) and human double minute 2 (HDM2) are negative regulators of P53. Herein, we examined the role of AURKA in regulating HDM2 and its subsequent effects on P53 apoptotic function in gastric cancer. EXPERIMENTAL DESIGN: Primary tumors and in vitro gastric cancer cell models with overexpression or knockdown of AURKA were used. The role of AURKA in regulating HDM2 and cell survival coupled with P53 expression and activity were investigated. RESULTS: Overexpression of AURKA enhanced the HDM2 protein level; conversely, knockdown of endogenous AURKA decreased expression of HDM2 in AGS and SNU-1 cells. Dual co-immunoprecipitation assay data indicated that AURKA was associated with HDM2 in a protein complex. The in vitro kinase assay using recombinant AURKA and HDM2 proteins followed by co-immunoprecipitation revealed that AURKA directly interacts and phosphorylates HDM2 protein in vitro. The activation of HDM2 by AURKA led to induction of P53 ubiquitination and attenuation of cisplatin-induced activation of P53 in gastric cancer cells. Inhibition of AURKA using an investigational small-molecule specific inhibitor, alisertib, decreased the HDM2 protein level and induced P53 transcriptional activity. These effects markedly decreased cell survival in vitro and xenograft tumor growth in vivo. Notably, analysis of immunohistochemistry on tissue microarrays revealed significant overexpression of AURKA and HDM2 in human gastric cancer samples (P < 0.05). CONCLUSION: Collectively, our novel findings indicate that AURKA promotes tumor growth and cell survival through regulation of HDM2-induced ubiquitination and inhibition of P53. Clin Cancer Res; 20(1); 76-86. (c)2013 AACR. PMID- 24240109 TI - Tumor growth rate is an early indicator of antitumor drug activity in phase I clinical trials. AB - PURPOSE: Response Evaluation Criteria in Solid Tumors (RECIST) evaluation does not take into account the pretreatment tumor kinetics and may provide incomplete information about experimental drug activity. Tumor growth rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. EXPERIMENTAL DESIGN: Medical records from all patients (N = 253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pretreatment period (reference) and the experimental period. Associations between TGR, standard prognostic scores [Royal Marsden Hospital (RMH) score], and outcome [progression-free survival (PFS) and overall survival (OS)] were computed (multivariate analysis). RESULTS: We observed a reduction of TGR between the reference versus experimental periods (38% vs. 4.4%; P < 0.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analysis, only the decrease of TGR was associated with PFS (P = 0.004), whereas the RMH score was the only variable associated with OS (P = 0.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P < 0.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity. CONCLUSIONS: Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) independent association with PFS; and (iii) it reveals drug-specific profiles, suggesting potential utility for guiding the further development of the investigational drugs. PMID- 24240110 TI - IgG-switched CLL has a distinct immunogenetic signature from the common MD variant: ontogenetic implications. AB - PURPOSE: Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. EXPERIMENTAL DESIGN: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively. RESULTS: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior. CONCLUSIONS: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. PMID- 24240111 TI - Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216. AB - PURPOSE: Constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors via either gene mutation in the p110alpha catalytic subunit of PI3K or functional loss of tumor suppressor PTEN. Patients with small-cell lung cancer (SCLC) have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. In this study, we characterized the highly selective oral PI3K inhibitor, PF 4989216, in preclinical SCLC models to investigate whether targeting the PI3K pathway is an effective targeted therapy option for SCLCs that harbor a PIK3CA mutation. EXPERIMENTAL DESIGN: A panel of SCLC cell lines with PIK3CA mutation or PTEN loss were treated with PF-4989216 in several in vitro assays, including PI3K pathway signaling, cell viability, apoptosis, cell-cycle progression, and cell transformation. SCLC cell lines that were sensitive in vitro to PF-4989216 were further evaluated by in vivo animal studies to determine the pharmacokinetic/pharmacodynamic relationship and tumor growth inhibition (TGI) by PF-4989216 treatment. RESULTS: PF-4989216 inhibited PI3K downstream signaling and subsequently led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in SCLCs harboring PIK3CA mutation. In SCLCs with PTEN loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator (BIM)-mediated apoptosis nor was there any effect on cell viability or transformation. These results implicate differential tumorigenesis and apoptosis mechanisms in SCLCs harboring PIK3CA mutation versus PTEN loss. CONCLUSIONS: Our results suggest that PF-4989216 is a potential cancer drug candidate for patients with SCLC with PIK3CA mutation but not PTEN loss. PMID- 24240112 TI - Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. AB - PURPOSE: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain. EXPERIMENTAL DESIGN: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway. RESULTS: Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation. CONCLUSIONS: Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials. PMID- 24240113 TI - MUC4-mediated regulation of acute phase protein lipocalin 2 through HER2/AKT/NF kappaB signaling in pancreatic cancer. AB - PURPOSE: MUC4 shows aberrant expression in early pancreatic lesions and a high specificity for pancreatic cancer. It thus has a high potential to be a sensitive and specific biomarker. Unfortunately, its low serum level limits its diagnostic/prognostic potential. We here report that a multifaceted acute phase protein lipocalin 2, regulated by MUC4, could be a potential diagnostic/prognostic marker for pancreatic cancer. Experimental Designs and RESULTS: Overexpression/knockdown, luciferase reporter and molecular inhibition studies revealed that MUC4 regulates lipocalin 2 by stabilizing HER2 and stimulating AKT, which results in the activation of NF-kappaB. Immunohistochemical analyses of lipocalin 2 and MUC4 showed a significant positive correlation between MUC4 and lipocalin 2 in primary, metastatic tissues (Spearman correlation coefficient 0.71, P = 0.002) from rapid autopsy tissue sample from patients with pancreatic cancer as well as in serum and tissue samples from spontaneous KRASG(12)D mouse pancreatic cancer model (Spearman correlation coefficient 0.98, P < 0.05). Lipocalin 2 levels increased progressively with disease advancement (344.2 +/- 22.8 ng/mL for 10 weeks to 3067.2 +/- 572.6 for 50 weeks; P < 0.0001). In human pancreatic cancer cases, significantly elevated levels of lipocalin 2 were observed in patients with pancreatic cancer (148 +/- 13.18 ng/mL) in comparison with controls (73.27 +/- 4.9 ng/mL, P = 0.014). Analyses of pre- and postchemotherapy patients showed higher lipocalin 2 levels in prechemotherapy patients [121.7 ng/mL; 95% confidence interval (CI), 98.1-150.9] in comparison with the postchemotherapy (92.6 ng/mL; 95% CI, 76.7-111.6; P = 0.06) group. CONCLUSIONS: This study delineates the association and the downstream mechanisms of MUC4-regulated elevation of lipocalin-2 (via HER2/AKT/NF-kappaB) and its clinical significance for prognosis of pancreatic cancer. PMID- 24240115 TI - Pertuzumab protects the achilles' heel of trastuzumab--emtansine. AB - Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2(+) breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization. PMID- 24240116 TI - Biosurfactant production by Bacillus subtilis B30 and its application in enhancing oil recovery. AB - The fermentative production of biosurfactants by Bacillus subtilis strain B30 and the evaluation of biosurfactant based enhanced oil recovery using core-flood were investigated. Different carbon sources (glucose, sucrose, starch, date molasses, cane molasses) were tested to determine the optimal biosurfactant production. The isolate B30 produced a biosurfactant that could reduce the surface tension and interfacial tension to 26.63+/-0.45 mN/m and 3.79+/-0.27 mN/m, respectively in less than 12h in both glucose or date molasses based media. A crude biosurfactant concentration of 0.3-0.5 g/l and critical micelle dilution (CMD) values of 1:8 were observed. The biosurfactants gave stable emulsions with wide range of hydrocarbons including light and heavy crude oil. The biosurfactants were partially purified and identified as a mixture of lipopeptides similar to surfactin, using high performance thin layer chromatography and Fourier transform infrared spectroscopy. The biosurfactants were stable over wide range of pH, salinity and temperatures. The crude biosurfactant preparation enhanced light oil recovery by 17-26% and heavy oil recovery by 31% in core-flood studies. The results are indicative of the potential of the strain for the development of ex situ microbial enhanced oil recovery processes using glucose or date molasses based minimal media. PMID- 24240114 TI - Neutrophils promote the malignant glioma phenotype through S100A4. AB - PURPOSE: Antiangiogenic therapy is effective in blocking vascular permeability, inhibiting vascular proliferation, and slowing tumor growth, but studies in multiple cancer types have shown that tumors eventually acquire resistance to blockade of blood vessel growth. Currently, the mechanisms by which this resistance occurs are not well understood. EXPERIMENTAL DESIGN: In this study, we evaluated the effects of neutrophils on glioma biology both in vitro and in vivo and determined target genes by which neutrophils promote the malignant glioma phenotype during anti-VEGF therapy. RESULTS: We found that an increase in neutrophil infiltration into tumors is significantly correlated with glioma grade and in glioblastoma with acquired resistance to anti-VEGF therapy. Our data demonstrate that neutrophils and their condition media increased the proliferation rate of glioblastoma-initiating cells (GIC). In addition, neutrophils significantly increased GICs Transwell migration compared with controls. Consistent with this behavior, coculture with neutrophils promoted GICs to adopt morphologic and gene expression changes consistent with a mesenchymal signature. Neutrophil-promoting tumor progression could be blocked by S100A4 downregulation in vitro and in vivo. Furthermore, S100A4 depletion increased the effectiveness of anti-VEGF therapy in glioma. CONCLUSIONS: Collectively, these data suggest that increased recruitment of neutrophils during anti-VEGF therapy promotes glioma progression and may promote treatment resistance. Tumor progression with mesenchymal characteristics is partly mediated by S100A4, the expression of which is increased by neutrophil infiltration. Targeting granulocytes and S100A4 may be effective approaches to inhibit the glioma malignant phenotype and diminish antiangiogenic therapy resistance. PMID- 24240117 TI - Exercise training in polycystic ovarian syndrome enhances flow-mediated dilation in the absence of changes in fatness. AB - INTRODUCTION: Polycystic ovarian syndrome (PCOS) is associated with an adverse cardiovascular disease (CVD) profile. A surrogate marker for CVD risk is endothelial dysfunction. Limited studies exist examining the cardiovascular and metabolic effects of exercise in PCOS and specifically its impact on endothelial function. Therefore, the aim of the current study was to investigate the impact of exercise on endothelial function, in parallel with body composition, insulin resistance, and cardiopulmonary fitness in PCOS. METHODS: Ten women with PCOS (27 yr, 95% confidence interval [CI] = 23-32; 31 kg.m-2, 95% CI = 28-34) completed a 16-wk exercise (EX) program, and seven women with PCOS (29 yr, 95% CI = 24-35; 35 kg.m-2, 95% CI = 31-40) undertook conventional care (CC) following lifestyle advice. Brachial artery endothelial function was assessed pre- and postintervention using flow-mediated dilation adjusted for variability in baseline diameter. Visceral and abdominal subcutaneous adipose tissue was assessed using whole-body magnetic resonance imaging and 1H magnetic resonance spectroscopy quantified liver fat. Cardiorespiratory fitness, glycemic control, hormone, and lipid profiles were also assessed. Data were analyzed using covariate-controlled generalized estimating equations. RESULTS: At follow-up, EX improved flow-mediated dilation by 3.6% (95% CI = 0.5-6.7, P = 0.03) more than CC. There was a parallel improvement in cardiorespiratory fitness of 4.7 mL.kg 1.min-1 (95% CI = 1.4-7.9, P < 0.001) with EX versus CC. These changes were not explained by changes in visceral adipose tissue, subcutaneous adipose tissue, liver fat or insulin resistance. CONCLUSIONS: Supervised exercise in women with PCOS improves endothelial function, an adaptation associated with reduced CVD risk. This change occurs independent of changes in body weight or composition. The success of public health interventions in this patient group should not be solely judged by weight loss. PMID- 24240118 TI - Influence of cold-water immersion on limb and cutaneous blood flow after exercise. AB - PURPOSE: This study aimed to determine the influence of cold (8 degrees C) and cool (22 degrees C) water immersion on femoral artery and cutaneous blood flow after exercise. METHODS: Twelve men completed a continuous cycle exercise protocol at 70% peak oxygen uptake until a core temperature of 38 degrees C was attained. Subjects were then immersed semireclined into 8 degrees C or 22 degrees C water to the iliac crest for 10 min or rested. Rectal and thigh skin temperature, deep and superficial muscle temperature, thigh and calf skin blood flow (laser Doppler flowmetry), and superficial femoral artery blood flow (duplex ultrasound) were measured before and up to 30 min after immersion. Indices of vascular conductance were calculated (flux and blood flow/mean arterial pressure). RESULTS: Reductions in rectal temperature were similar (0.6 degrees C 0.7 degrees C) in all three trials (P = 0.38). The mean +/- SD thigh skin temperature during recovery was 25.4 degrees C +/- 3.8 degrees C in the 8 degrees C trial, which was lower than the 28.2 degrees C +/- 1.4 degrees C and 33.78 degrees C +/- 1.0 degrees C in the 22 degrees C and control trials, respectively (P < 0.001). Recovery muscle temperature was also lowest in the 8 degrees C trial (P < 0.01). Femoral artery conductance was similar after immersion in both cooling conditions and was lower (~55%) compared with the control condition 30 min after immersion (P < 0.01). Similarly, there was greater thigh (P < 0.01) and calf (P < 0.05) cutaneous vasoconstriction during and after immersion in both cooling conditions relative to the control condition. CONCLUSION: Colder water temperatures may be more effective in the treatment of exercise-induced muscle damage and injury rehabilitation by virtue of greater reductions in muscle temperature and not muscle blood flow. PMID- 24240119 TI - Reposition acuity and postural control after exercise in anterior cruciate ligament reconstructed knees. AB - PURPOSE: This study aimed to compare the effects of 36 min of continuous exercise on postural control and joint reposition acuity in patients with anterior cruciate ligament reconstruction (ACL-R) and healthy controls. METHODS: Twenty patients (10 women and 10 men; mean +/- SD; age = 25.5 +/- 5.5 yr, height = 1.75 +/- 0.10 m, weight = 76.7 +/- 14.4 kg) with a history of primary, uncomplicated ACL-R (5.0 +/- 4.3 yr postsurgery) were matched to 20 healthy controls (10 women and 10 men, 24.6 +/- 5.0 yr, 1.70 +/- 0.09 m, 65.2 +/- 12.1 kg). The center of pressure (COP) excursions in the medial-lateral (COP(ML-SD)) and anterior posterior (COP(AP-SD)) directions and the velocity (COP(Vel)) and area (COP(Area)) were calculated during static, unipedal stance. Open-chain knee joint reposition acuity measures (absolute angular error [AAE] and relative angular error [RAE]) at 45 degrees (AAE45 and RAE45) and 15 degrees of knee flexion (AAE15 and RAE15) were recorded. Measures were recorded at baseline and after a 36-min exercise protocol. Exercise consisted of six repeating cycles of inclined treadmill walking (5 min) and jumping exercises (1 min). RESULTS: At baseline, the ACL-R group exhibited higher magnitude AAE45 compared with controls. AAE45 and COP(ML-SD) significantly increased after exercise in the control group; however, the ACL-R group did not experience a change in these measures. CONCLUSIONS: In a rested state, patients with a history of ACL-R have greater impairment in joint reposition acuity than healthy control. Exercise increased COP measurements and impaired joint reposition acuity. Healthy controls experienced impaired joint reposition acuity after exercise, whereas patients with a history of ACL-R did not. PMID- 24240120 TI - Selected issues for nutrition and the athlete: a team physician consensus statement. PMID- 24240122 TI - Androgen insensitivity syndrome diagnosed in an elderly patient during a strangulated inguinal hernia repair. AB - INTRODUCTION: A strangulated inguinal hernia is a common indication for emergency surgery. In comparison, complete testicular feminization is a rare genetic disease that can present with an inguinal hernia because of ectopically positioned testicles. PRESENTATION OF CASE: A 70-year-old female was admitted to the emergency service complaining of a painful swelling in the right inguinal region for 1 day. The physical examination indicated a strangulated inguinal hernia and surgery was performed. On exploring the inguinal region, a strangulated indirect inguinal hernia and hard 2*3-cm mass were detected. The histopathological examination of the excised mass showed testicular tissue, and complete testicular feminization (CTF) was diagnosed after further examinations. DISCUSSION: Androgen insensitivity syndrome (AIS), the most frequent cause of male pseudohermaphroditism. The diagnosis of patients with AIS is usually made at the beginning of the second decade when a healthy person with a female phenotype complains of no menarche. Making a first diagnosis after the 5th decade is extremely rare. CONCLUSION: While AIS can be diagnosed in early adulthood, cases might not bediagnosed until the patient is of advanced age. PMID- 24240123 TI - Selective expansion of human natural killer cells leads to enhanced alloreactivity. AB - In allogeneic stem cell transplantation (SCT), natural killer (NK) cells lacking their cognate inhibitory ligand can induce graft-versus-leukemia responses, without the induction of severe graft-versus-host disease (GVHD). This feature can be exploited for cellular immunotherapy. In this study, we examined selective expansion of NK cell subsets expressing distinct killer immunoglobulin-like receptors (KIRs) within the whole human peripheral blood NK cell population, in the presence of HLA-Cw3 (C1) or Cw4 (C2) transfected K562 stimulator cells. Coculture of KIR(+) NK cells with C1 or C2 positive K562 cells, in the presence of IL-2+IL-15, triggered the outgrowth of NK cells that missed their cognate ligand. This resulted in an increased frequency of alloreactive KIR(+) NK cells within the whole NK cell population. Also, after preculture with K562 cells lacking their cognate ligand, we observed that this alloreactive NK population revealed higher numbers of CD107(+) cells when cocultured with the relevant K562 HLA-C transfected target cells, as compared to coculture with untransfected K562 cells. This enhanced reactivity was confirmed using primary leukemic cells as target. This study demonstrates that HLA class I expression can mediate the skewing of the NK cell repertoire and enrich the population for cells with enhanced alloreactivity towards leukemic target cells. This feature may support future clinical applications of NK cell-based immunotherapy. PMID- 24240121 TI - Computational methods for detecting copy number variations in cancer genome using next generation sequencing: principles and challenges. AB - Accurate detection of somatic copy number variations (CNVs) is an essential part of cancer genome analysis, and plays an important role in oncotarget identifications. Next generation sequencing (NGS) holds the promise to revolutionize somatic CNV detection. In this review, we provide an overview of current analytic tools used for CNV detection in NGS-based cancer studies. We summarize the NGS data types used for CNV detection, decipher the principles for data preprocessing, segmentation, and interpretation, and discuss the challenges in somatic CNV detection. This review aims to provide a guide to the analytic tools used in NGS-based cancer CNV studies, and to discuss the important factors that researchers need to consider when analyzing NGS data for somatic CNV detections. PMID- 24240125 TI - Nitric oxide drives embryonic myogenesis in chicken through the upregulation of myogenic differentiation factors. AB - The muscle-specific variant of neuronal nitric oxide (NO) synthase (NOS-I), is developmentally regulated in mouse suggesting a role of NO during myogenesis. In chick embryo, a good model of development, we found that the expression of NOS-I is up-regulated, but only in the early phase of development. Through a pharmacological intervention in ovo we found that NO signalling plays a relevant role during embryonic development. The inhibition of NOS-I decreased the growth of embryo, in particular of muscle tissue, while the restoring of physiological NO levels, via administration of a NO donor, reversed this effect. We found a selective action of NO, produced by NOS-I, on regulatory factors involved in myogenic differentiation in the early phase of chick embryo development: inhibition of NO generation leads to a decreased expression of the Myocyte enhancer factor 2a (Mef2a), Mef2c, Myogenin and Myosin, which was reversed by the administration of a NO donor. NO had no effects on Myf5 and MyoD, the myogenic regulatory factors necessary for myogenic determination. The action of NO on the myogenic regulatory factors was mediated via generation of cyclic GMP (cGMP) and activation of the cGMP-dependent protein kinase G (PKG). Finally we found in myoblasts in vitro that the activation of Mef2c was the key event mediating the NO-induced modulation of myogenesis. Our results identify NO produced by NOS-I as a key messenger in the early phase of embryonic development of chicken, acting as a critical determinant of myogenesis through its physiological cGMP/PKG pathway. PMID- 24240124 TI - MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFkappaB activation in vitro. AB - Epigenetic factors, including altered microRNA (miRNA) expression, may contribute to aberrant immune cell function in systemic lupus erythematosus (SLE). MiRNA-let 7a (let-7a) has been shown to directly alter cell cycle progression and proinflammatory cytokine production. Due to the crucial role of let-7a in cell division and inflammation, we investigated let-7a-mediated proliferation and NFkappaB translocation in J774A.1 macrophages and MES 13 mesangial cells in vitro. In immune-stimulated cells transfected with let-7a, cell proliferation was significantly increased over time. There was a significant increase in the number of immune-stimulated cells in S and G2 phases. Immune-stimulated cells overexpressing let-7a had increased nuclear translocation of NFkappaB. Bioinformatical analysis revealed that the E2F family, critical regulators of the G1-S transition, has potential binding sites for let-7a in their mRNA transcripts. Let-7a overexpression significantly increased the expression of the cell cycle activator E2F2 and increased retinoblastoma protein (Rb) phosphorylation in immune-stimulated cells. The cell cycle inhibitor E2F5 was significantly decreased in let-7a-transfected cells that were immune-stimulated. Bioinformatical analysis revealed E2F2 and NFkappaB are transcription factors predicted to regulate the let-7a promoter. We analyzed transcriptional regulation of let-7a by real-time RT-PCR using chromatin immunoprecipitation with E2F2 and NFkappaB antibodies. There was an increase in E2F2 and NFkappaB binding in DNA enriched for the let-7a promoter in immune-stimulated cells. Silencing E2F2 or NFkappaB significantly decreased let-7a expression and IL-6 production in immune stimulated cells. Taken together, our results suggest that overexpression of let 7a may contribute to hyperplasia and the proinflammatory response in SLE. PMID- 24240126 TI - Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development. AB - Toward developing biologically sound models for the study of heart regeneration and disease, we cultured heart cells on a biodegradable, microfabricated poly(glycerol sebacate) (PGS) scaffold designed with micro-structural features and anisotropic mechanical properties to promote cardiac-like tissue architecture. Using this biomimetic system, we studied individual and combined effects of supplemental insulin-like growth factor-1 (IGF-1) and electrical stimulation (ES). On culture day 8, all tissue constructs could be paced and expressed the cardiac protein troponin-T. IGF-1 reduced apoptosis, promoted cell to-cell connectivity, and lowered excitation threshold, an index of electrophysiological activity. ES promoted formation of tissue-like bundles oriented in parallel to the electrical field and a more than ten-fold increase in matrix metalloprotease-2 (MMP-2) gene expression. The combination of IGF-1 and ES increased 2D projection length, an index of overall contraction strength, and enhanced expression of the gap junction protein connexin-43 and sarcomere development. This culture environment, designed to combine cardiac-like scaffold architecture and biomechanics with molecular and biophysical signals, enabled functional assembly of engineered heart muscle from dissociated cells and could serve as a template for future studies on the hierarchy of various signaling domains relative to cardiac tissue development. PMID- 24240127 TI - The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells. AB - Recent reports suggest that N-methyl-d-aspartate receptor (NMDAR) blockade by MK 801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. PMID- 24240129 TI - Chronic cough: an otorhinolaryngology perspective. AB - PURPOSE OF REVIEW: Cough lasting more than 8 weeks is a common presenting complaint to the otolaryngologist. Historically, chronic cough has been attributed to post-nasal drip, laryngopharyngeal reflux and cough-variant asthma. This study reviews chronic cough from the viewpoint of an otolaryngologist. RECENT FINDINGS: More recent studies suggest the influence of laryngeal neuropathy and its interplay with laryngopharyngeal reflux. There is limited evidence for post-nasal drip or cough-variant asthma causing chronic cough. SUMMARY: In this study, we review the evidence for cause of chronic cough, as well as up to date techniques for the otolaryngologist, including transnasal esophagoscopy, to assess the patient in clinic allowing accurate diagnosis. Treatment options for the otolaryngologist are discussed and the role of multidisciplinary input emphasized. PMID- 24240131 TI - Dysmotility and reflux disease. AB - PURPOSE OF REVIEW: In the last decade, with the advent of new oesophageal testing [i.e. 24-h impedance-pH monitoring, combined impedance-manometry, high-resolution manometry (HRM)], relevant progress in understanding the mechanisms contributing to the development of gastro-oesophageal reflux disease (GORD) has been made, allowing a better management of patients with this disorder. The aim of our review is to report the state-of-the-art about oesophageal motor disorders in patients with reflux disease and to stimulate new research in this field. RECENT FINDINGS: Hypotensive lower oesophageal sphincter (LOS), transient LOS relaxations, impairment of oesophagogastric junction including hiatal hernia, oesophageal bolus transit abnormalities and presence of ineffective oesophageal motility have been strongly implicated in GORD development. In particular, the majority of recent studies carried out with HRM and impedance-pH testing reported that these motor abnormalities are increasingly prevalent with increasing severity of GORD, from nonerosive reflux disease and erosive oesophagitis to Barrett's oesophagus. SUMMARY: Defining and characterizing oesophageal dysmotility in patients with reflux disease is of maximum importance in order to properly diagnose these patients and to treat them with the best management of care. New studies are needed in order to better understand the physiomechanic basis of oesophageal dysmotility in GORD patients. PMID- 24240130 TI - Chronic cough: a gastroenterology perspective. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight recent work and provide recommendations on the approach for diagnosis and management of chronic cough in a gastroenterology clinic. RECENT FINDINGS: Chronic cough is a burdensome symptom affecting a large number of patients and contributes significant cost to the healthcare system. Recent work has shown that select patients may benefit from acid-suppressive therapy and even surgery when there is true pathologic evidence of reflux disease with cough. However, judicious use and proper interpretation of diagnostic testing for gastroesophageal reflux in the setting of cough is important to avoid unnecessary or inappropriate therapy. SUMMARY: Chronic cough remains a vexing problem for many physicians, including gastroenterologists. It is important that physicians approach refractory cough in a multidisciplinary manner. Future research is needed to better understand the likely central hypersensitivity response mediating reflux-related cough and potential alternative approaches to therapy. PMID- 24240132 TI - Pediatric sleep studies: when and how often are they necessary? AB - PURPOSE OF REVIEW: With the increased awareness of the morbidity associated with snoring, polysomnography (PSG) is becoming more prevalent. Many national organizations have recently published clinical guidelines to facilitate decision making for children with disrupted breathing patterns. This review will discuss these clinical guidelines and describe the rationale behind them. It will also touch on the limitations of PSG. RECENT FINDINGS: The common theme for the clinical guidelines is that PSG is being underutilized. Not only is obstructive sleep apnea (OSA) associated with behavioral, cognitive, and cardiovascular morbidity, but primary snoring is also not always benign. The interpretation of the PSG is influenced by multiple variables: filter settings, sensors utilized, and how the respiratory events are tabulated. SUMMARY: To diagnose OSA, one requires overnight PSG. Multiple guidelines have been published to facilitate decision-making. Many questions remain unanswered and future research as well as PSG standardization will further clarify the role of PSG in the evaluation and treatment of disrupted breathing patterns in children. PMID- 24240133 TI - Paediatric cervical lymphadenopathy: when to biopsy? AB - PURPOSE OF REVIEW: Cervical lymphadenopathy is common in the paediatric population and persistent lymphadenopathy of unknown cause is a frequent reason for otolaryngology referral. Diagnostic work-up is variable among physicians and deciding when excisional biopsy is necessary remains a challenge. This update reviews the recent literature on the work-up and diagnosis of paediatric cervical lymphadenopathy, with a focus on factors that may influence the need for excisional biopsy. RECENT FINDINGS: The majority of paediatric cervical lymphadenopathy cases are benign, with infection and reactive lymphoid hyperplasia being far more common than malignancy. Ultrasound is the initial imaging modality of choice for paediatric cervical lymphadenopathy and can provide critical information to aid in diagnosis. Clinical factors that may predict malignancy include lymph node size greater than 2 cm, multiple levels of adenopathy and supraclavicular location. Biopsy should be strongly considered in patients with a combination of these factors or other suspicious findings such as severe systemic symptoms. SUMMARY: Paediatric cervical lymphadenopathy is commonly encountered in general and paediatric otolaryngology practice; however, absolute guidelines for biopsy do not exist. Careful consideration of history, physical examination, laboratory work-up and diagnostic imaging must be used to guide the clinician in decision-making for biopsy. PMID- 24240128 TI - Aging is not programmed: genetic pseudo-program is a shadow of developmental growth. AB - Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways such as mTOR. Ironically, this is often misunderstood as a sort of programmed aging. In contrast, aging is a purposeless quasi-program or, figuratively, a shadow of actual programs. PMID- 24240134 TI - Cricopharyngeal achalasia in children: indications for treatment and management options. AB - PURPOSE OF REVIEW: Cricopharyngeal achalasia (CPA) is an infrequently encountered but important diagnosis in pediatric dysphagia. This disorder is characterized by difficulty in feeding, regurgitation of feeds, and recurrent aspiration episodes. In this review, we discuss the current understanding of the pathophysiology of the disease and the recent developments in the diagnosis and therapeutic management of CPA. RECENT FINDINGS: Because of the rarity of the disease, the literature reporting the treatment of CPA is limited to small case series. Although open surgical treatments including cricopharyngeal myotomy have been reported in the past, recent studies advocate less-invasive endoscopic approaches, including balloon dilation, endoscopic cricopharyngeal myotomy, and botulinum toxin injections. SUMMARY: When CPA is suspected as a cause of dysphagia in a child, the diagnosis can be confirmed with videofluoroscopic swallow studies that demonstrate narrowing at the region of the cricopharyngeus muscle. Treatment should be initiated for children who are unable to feed orally. Current options for treatment include botulinum toxin injections, endoscopic balloon dilation, and open or endoscopic cricopharyngeal myotomy. All techniques have shown success in the treatment of the disease. Further studies comparing treatment modalities are needed before a clear recommendation can be made. PMID- 24240136 TI - Cognitive control in context: working memory capacity and proactive control. AB - Working memory is important for maintaining critical information in an active state to guide future behavior. The executive-attention theory of working memory capacity (WMC; Engle & Kane, 2004) argues that goal maintenance is important for response selection when stimuli are associated with competing responses. Braver, Burgess, and Gray (2007) have labeled this type of preparatory activity proactive control. Previous WMC studies have not allowed individuals to use goal information to prepare a specific response in advance of the stimulus. The current experiment used different versions of a cue-probe task to examine the relationship between individual differences in WMC and proactive control. Across three versions of the AX version of the Continuous Performance Test, the proportion of targets was manipulated to affect both the predictive validity of the A cue and the prepotency of the target response to X probes. The results indicated that the high-WMC individuals used the cue information to prepare responses in advance only when a specific probe was likely to occur. In contrast, the performance of the low-WMC individuals was less dependent upon the cue and more contingent upon overall response frequencies. The results indicate that individual differences in WMC are related to proactive control and anticipation, and important for translating cognition into action. PMID- 24240137 TI - FDG-PET/CT-based restaging may alter initial management decisions and clinical outcomes in patients with locally advanced pancreatic carcinoma planned to undergo chemoradiotherapy. AB - The impact of [(18)F]fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) restaging on management decisions and outcomes in patients with locally advanced pancreatic carcinoma (LAPC) scheduled for concurrent chemoradiotherapy (CRT) is examined. Seventy-one consecutive patients with conventionally staged LAPC were restaged with PET/CT before CRT, and were categorized into non-metastatic (M0) and metastatic (M1) groups. M0 patients received 50.4 Gy CRT with 5-fluorouracil followed by maintenance gemcitabine, whereas M1 patients received chemotherapy immediately or after palliative radiotherapy. In 19 patients (26.8%), PET/CT restaging showed distant metastases not detected by conventional staging. PET/CT restaging of M0 patients showed additional regional lymph nodes in 3 patients and tumors larger than CT-defined borders in 4. PET/CT therefore altered or revised initial management decisions in 26 (36.6%) patients. At median follow-up times of 11.3, 14.5, and 6.2 months for the entire cohort and the M0 and M1 cohorts, respectively, median overall survival was 16.1, 11.4, and 6.2 months, respectively; median locoregional progression-free survival was 9.9, 7.8, and 3.4 months, respectively; and median progression-free survival was 7.4, 5.1, and 2.5 months, respectively (P < 0.05 each). These findings suggest that PET/CT-based restaging may help select patients suitable for CRT, sparing those with metastases from futile radical protocols, and increasing the accuracy of estimated survival. PMID- 24240138 TI - Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study). AB - OBJECTIVES: Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. DESIGN: The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. SETTING AND PARTICIPANTS: Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. OUTCOME MEASURES: PRIMARY OUTCOME: weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. RESULTS: Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). CONCLUSIONS: Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe. PMID- 24240139 TI - A reliability study of colour-Doppler sonography for the diagnosis of chronic cerebrospinal venous insufficiency shows low inter-rater agreement. AB - OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) has been extremely variable, associated with multiple sclerosis in colour-Doppler sonographic studies. We aimed to evaluate inter-rater agreement in a colour-Doppler sonography venous examination. DESIGN: Inter-rater agreement study. SETTING: First-referral multiple sclerosis centre. PARTICIPANTS: 38 patients with multiple sclerosis and 55 age-matched (+/-5 years) controls. INTERVENTION: Sonography was carried out in accordance with Zamboni's five criteria by eight sonographers with different expertise, blinded to the status of cases and controls. Each participant was evaluated by two operators. PRIMARY AND SECONDARY OUTCOME MEASURES: Inter-rater agreement was measured through the kappa statistics and the intraclass correlation coefficient. RESULTS: The agreement was no higher than chance for criterion 2-reflux in the deep cerebral veins (kappa=-0.02) and criterion 4-flow not Doppler detectable in one or both the internal jugular veins (IJVs) or vertebral veins (VVs; -0.09). It was substantially low for criterion 1 reflux in the IJVs and/or VVs (0.29), criterion 3-IJV stenosis or malformations (0.23) and criterion 5-absence of IJV diameter increase when passing from the sitting to the supine position (0.22). The kappa value for CCSVI as a whole was 0.20 (95% confidence limit -0.01 to 0.42). Intraclass correlation coefficients for the measure of cross-sectional area ranged from 0.05 to 0.25. Inter-rater agreement was low for CCSVI experts (kappa=0.24; -0.11 to 0.59) and non-experts (0.20; -0.33 to 0.73); neurologists (0.21; -0.06 to 0.47) and non-neurologists (0.18; -0.20 to 0.56); cases (0.19; -0.14 to 0.52) and controls (0.21; -0.08 to 0.49). Zamboni-trained neurosonographers ascertained CCSVI more frequently than the non-trained neurosonographers. CONCLUSIONS: Agreement was unsatisfactory for the diagnosis of CCSVI as a whole, for each of its five criteria and according to the different subgroups. Standardisation of the method is urgently needed prior to its further application in studies of patients with multiple sclerosis or other neurological diseases. PMID- 24240140 TI - Fidelity in complex behaviour change interventions: a standardised approach to evaluate intervention integrity. AB - OBJECTIVES: The aim of this study was to (1) demonstrate the development and testing of tools and procedures designed to monitor and assess the integrity of a complex intervention for chronic pain (COping with persistent Pain, Effectiveness Research into Self-management (COPERS) course); and (2) make recommendations based on our experiences. DESIGN: Fidelity assessment of a two-arm randomised controlled trial intervention, assessing the adherence and competence of the facilitators delivering the intervention. SETTING: The intervention was delivered in the community in two centres in the UK: one inner city and one a mix of rural and urban locations. PARTICIPANTS: 403 people with chronic musculoskeletal pain were enrolled in the intervention arm and 300 attended the self-management course. Thirty lay and healthcare professionals were trained and 24 delivered the courses (2 per course). We ran 31 courses for up to 16 people per course and all were audio recorded. INTERVENTIONS: The course was run over three and a half days; facilitators delivered a semistructured manualised course. OUTCOMES: We designed three measures to evaluate fidelity assessing adherence to the manual, competence and overall impression. RESULTS: We evaluated a random sample of four components from each course (n=122). The evaluation forms were reliable and had good face validity. There were high levels of adherence in the delivery: overall adherence was two (maximum 2, IQR 1.67-2.00), facilitator competence exhibited more variability, and overall competence was 1.5 (maximum 2, IQR 1.25-2.00). Overall impression was three (maximum 4, IQR 2.00-3.00). CONCLUSIONS: Monitoring and assessing adherence and competence at the point of intervention delivery can be realised most efficiently by embedding the principles of fidelity measurement within the design stage of complex interventions and the training and assessment of those delivering the intervention. More work is necessary to ensure that more robust systems of fidelity evaluation accompany the growth of complex interventions. TRIAL REGISTRATION ISRCTN NO: ISRCTN24426731. PMID- 24240141 TI - Evidence for the aetiology of human papillomavirus in oesophageal squamous cell carcinoma in the Chinese population: a meta-analysis. AB - OBJECTIVES: We aimed to conduct a meta-analysis of human papillomavirus (HPV) as a risk factor for oesophageal squamous cell carcinoma (OSCC) in China, using all eligible studies published in the English and Chinese language literature. DESIGN: The random effect model was used to analyse the pooled OR. The I(2) and Q tests were included in the subgroup analyses. SETTING: Literature searches of databases including MEDLINE, PUBMED, EMBASE and Chinese National Knowledge Infrastructure (CNKI) and other available resources were performed to retrieve studies investigating OSCC tissue from Chinese participants for the presence of HPV DNA. PRIMARY OUTCOME MEASURE: A collective analysis of OSCC cases and control specimens was carried out from 15 case-control studies (6 in the English language and 9 in the Chinese language) for HPV prevalence. RESULTS: Of a total of 1177 OSCC and 1648 oesophageal control samples, 55% (642/1177) of cancer specimens and 27% (445/1648) of control samples were positive for HPV DNA. A positive strong association between HPV DNA and OSCC was observed among the included studies, with a pooled OR of 3.69 (95% CI 2.74 to 4.96). Heterogeneity and publication bias were not observed in the analysis. Subgroup analyses of the included studies also supported the measure of association of causal links between HPV and OSCC. CONCLUSIONS: This meta-analysis provides the strongest evidence until now of an association between HPV and OSCC in the Chinese population. China has a high burden of OSCC, making this an important research finding. A strength and new contribution of this study is combining data from the English and Chinese language literature to analyse all studies conducted in China. These findings may inform the population level use of prophylactic HPV vaccination to reduce the burden of OSCC in China. PMID- 24240142 TI - Nurse and manager perceptions of nurse initiated and managed antiretroviral therapy (NIMART) implementation in South Africa: a qualitative study. AB - OBJECTIVE: To explore nurse and facility and programme manager perceptions of nurse initiated and managed antiretroviral therapy (NIMART) implementation in Gauteng, South Africa. DESIGN: In this qualitative study, in-depth interviews and focus group discussions were conducted to gain insight into participants' experiences of NIMART implementation. SETTING: Participants came from urban, peri urban and rural primary healthcare clinics in two Gauteng Province municipalities. PARTICIPANTS: 25 nurses and 18 managers who were actively involved in NIMART implementation were purposively sampled. RESULTS: The findings from this study reveal that, despite encountering numerous challenges including human resources, training and clinical mentoring and health systems issues, NIMART nurses and managers remained optimistic about their work. Study participants felt empowered by their expanded roles. Increased responsibilities associated with NIMART implementation encouraged better use of creative problem solving and teamwork to facilitate integration of NIMART into existing clinic services. NIMART nurses perceived antiretroviral therapy (ART) patients to be more insightful about their illness, engaged in their HIV treatment and aware of the importance of adherence which enhanced nurse-patient relationships and increased their sense of job satisfaction. CONCLUSIONS: Although the implementation of NIMART is complex, when NIMART is implemented well, ART access is increased and patient outcomes are improved. Supportive interventions which address the specific challenges faced by nurses providing NIMART now need to be implemented. Attempts should be made to replicate the positive aspects of NIMART implementation identified by participants as this may improve healthcare providers' experiences of task-shifting. PMID- 24240143 TI - Epidemiology of time-loss injuries in English community-level rugby union. AB - OBJECTIVES: Using a prospective cohort study design, to establish the incidence and nature of time-loss injuries in English community rugby and to assess the differences between different playing levels. SETTING: English community rugby clubs. PARTICIPANTS: Injury information for 4635 matches was collected during seasons 2009/2010 (46 clubs), 2010/2011(67 clubs) and 2011/2012 (76 clubs). Clubs were subdivided into groups A (semiprofessional), B (amateur) and C (recreational) for analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Any injury resulting in 8 days or greater absence from match play was reported by injury management staff at the clubs. The primary outcome measure was injury incidence (per 1000 player match-hours) and the secondary outcome measure was severity (ie, days absence). RESULTS: Overall match injury incidence was 16.9 injuries per 1000 player match-hours. Incidence was higher for group A (21.7; 95% CI 19.8 to 23.6) compared with group B (16.6; 95% CI 15.2 to 17.9) and C (14.2; 95% CI 13.0 to 15.5, both p<0.001). The mean time-loss was 7.6 weeks absence, with knee and shoulder injuries the most severe with mean absences of 11.6 and 9.3 weeks, respectively. Half of all injuries occurred to the lower limb, with knee and ankle joint/ligament injuries the most common diagnoses. Shoulder joint/ligament injuries were the most common and severe upper limb injuries. Contact events accounted for 80% of all injuries and tackles accounted for 50%. Running was the most common non-contact injury event, of which 56% were hamstring injuries. CONCLUSIONS: More time-loss injuries occur at higher levels of community rugby. Injury prevention strategies should focus on good technique in the tackle and conditioning exercises for the knee, ankle, hamstrings and shoulder. PMID- 24240144 TI - How does provider supply and regulation influence health care markets? Evidence from nurse practitioners and physician assistants. AB - Nurse practitioners (NPs) and physician assistants (PAs) now outnumber family practice doctors in the United States and are the principal providers of primary care to many communities. Recent growth of these professions has occurred amidst considerable cross-state variation in their regulation, with some states permitting autonomous practice and others mandating extensive physician oversight. I find that expanded NP and PA supply has had minimal impact on the office-based healthcare market overall, but utilization has been modestly more responsive to supply increases in states permitting greater autonomy. Results suggest the importance of laws impacting the division of labor, not just its quantity. PMID- 24240145 TI - Removing financial barriers to organ and bone marrow donation: the effect of leave and tax legislation in the U.S. AB - Many U.S. states have passed legislation providing leave to organ and bone marrow donors and/or tax benefits for live and deceased organ and bone marrow donations and to employers of donors. We exploit cross-state variation in the timing of such legislation to analyze its impact on organ donations by living and deceased persons, on measures of the quality of the transplants, and on the number of bone marrow donations. We find that these provisions do not have a significant impact on the quantity of organs donated. The leave laws, however, do have a positive impact on bone marrow donations, and the effect increases with the size of the population of beneficiaries and with the generosity of the legislative provisions. Our results suggest that this legislation works for moderately invasive procedures such as bone marrow donation, but these incentives may be too low for organ donation, which is riskier and more burdensome. PMID- 24240147 TI - Conventional and microwave pyrolysis of a macroalgae waste from the Agar-Agar industry. Prospects for bio-fuel production. AB - A comparative study of the pyrolysis of a macroalgae industrial solid waste (algae meal) in an electrical conventional furnace and in a microwave furnace has been carried out. It was found that the chars obtained from both pyrolyses are similar and show good properties for performing as a solid bio-fuel and as a precursor of activated carbon. Bio-oils from conventional pyrolysis have a greater number of phenolic, pyrrole and alkane compounds whereas benzene and pyridine compounds are more predominant in microwave pyrolysis with a major presence of light compounds. The bio-gas fraction from microwave pyrolysis presents a much higher syngas content (H2+CO), and a lower CO2 and CH4 proportion than that obtained by conventional pyrolysis. Yields are similar for both treatments with a slightly higher gas yield in the case of microwave pyrolysis due to the fact that microwave heating favors heterogeneous reactions between the gases and the char. PMID- 24240146 TI - Mycelium differentiation and development of Streptomyces coelicolor in lab-scale bioreactors: programmed cell death, differentiation, and lysis are closely linked to undecylprodigiosin and actinorhodin production. AB - Streptomycetes are mycelium-forming bacteria that produce two thirds of clinically relevant secondary metabolites. Secondary metabolite production is activated at specific developmental stages of Streptomyces life cycle. Despite this, Streptomyces differentiation in industrial bioreactors tends to be underestimated and the most important parameters managed are only indirectly related to differentiation: modifications to the culture media, optimization of productive strains by random or directed mutagenesis, analysis of biophysical parameters, etc. In this work the relationship between differentiation and antibiotic production in lab-scale bioreactors was defined. Streptomyces coelicolor was used as a model strain. Morphological differentiation was comparable to that occurring during pre-sporulation stages in solid cultures: an initial compartmentalized mycelium suffers a programmed cell death, and remaining viable segments then differentiate to a second multinucleated antibiotic producing mycelium. Differentiation was demonstrated to be one of the keys to interpreting biophysical fermentation parameters and to rationalizing the optimization of secondary metabolite production in bioreactors. PMID- 24240148 TI - Characterization of calcium oxide catalysts from natural sources and their application in the transesterification of sunflower oil. AB - The catalytic activities of calcium oxide obtained from natural sources (crab shell and eggshell) were characterized and evaluated in the transesterification of vegetable oil. These catalysts are mainly composed of calcium carbonate, which is partially converted into CaO after calcination (900 degrees C for 2h). The catalysts have some advantages, such as abundant occurrence, low cost, porous structure, and nontoxic. The materials were characterized by XRD, FTIR, TG/DTG, CO2-TPD, XPS, SEM, and BET methods. The thermal treatment produces small particles of CaCO3 and CaO that are responsible for the catalytic activity. The conversion from triglycerides to methyl ester was not observed in transesterification carried out using natural crab shell and eggshell. Under optimized reaction conditions, the conversions to YFAME using the calcined catalysts were: crab shell (83.10+/-0.27 wt.%) and eggshell (97.75+/-0.02 wt.%). These results, showed that these materials have promising viability in transesterification for biodiesel production. PMID- 24240149 TI - Job-search basics: a scientific approach to interviewing. PMID- 24240150 TI - Loss of translation: a stealth weapon against pathogens? PMID- 24240151 TI - Influenza vaccines: mTOR inhibition surprisingly leads to protection. PMID- 24240152 TI - Kinases conquer the inflammasomes. PMID- 24240153 TI - A HESitant decision for T cells. PMID- 24240161 TI - Addendum: IgE+ memory B cells and plasma cells generated through a germinal center pathway. PMID- 24240160 TI - A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. AB - PD-1, a negative coreceptor expressed on antigen-stimulated T cells and B cells, seems to serve as a 'rheostat' of the immune response. The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain specific autoimmune phenotypes of PD-1-deficient mice, in contrast to the devastating fatal autoimmune disease of mice deficient in the immunomodulatory receptor CTLA-4, suggest that immunoregulation by PD-1 is rather antigen specific and is mainly cell intrinsic. Such unique properties make PD-1 a powerful target for immunological therapy, with highly effective clinical applications for cancer treatment. PMID- 24240162 TI - Direct detection of hyaluronidase in urine using cationic gold nanoparticles: a potential diagnostic test for bladder cancer. AB - Hyaluronidase (HAase) was reported as a urinary marker of bladder cancer. In this study, a simple colorimetric gold nanoparticle (AuNP) assay was developed for rapid and sensitive detection of urinary HAase activity. Charge interaction between polyanionic hyaluronic acid (HA) and cationic AuNPs stabilized with cetyl trimethyl ammonium bromide (CTAB) led to formation of gold aggregates and a red to blue color shift. HAase digests HA into small fragments preventing the aggregation of cationic AuNPs. The nonspecific aggregation of AuNPs in urine samples was overcome by pre-treatment of samples with the polycationic chitosan that was able to agglomerate all negatively charged interfering moieties before performing the assay. The developed AuNP assay was compared with zymography for qualitative detection of urinary HAase activity in 40 bladder carcinoma patients, 11 benign bladder lesions patients and 15 normal individuals, the assay sensitivity was 82.5% vs. 65% for zymography, while the specificity for both assays was 96.1%. The absorption ratio, A530/A620 of the reacted AuNP solution was used to quantify the HAase activity. The best cut off value was 93.5 MUU/ng protein, at which the sensitivity was 90% and the specificity was 80.8%.The developed colorimetric AuNP HAase assay is simple, inexpensive, and can aid noninvasive diagnosis of bladder cancer. PMID- 24240163 TI - A single fluorescent protein-based sensor for in vivo 2-oxogluatarate detection in cell. AB - 2-Oxoglutarate (2OG) is an important currency stands at the crossroad between carbon and nitrogen metabolism. Recent research found that 2OG acts as a signal in the regulation of nitrogen metabolism in prokaryote. While in eukaryotic cells, 2OG is also attractive since tricarboxylic acid cycle (TCA cycle) in tumor cells was found to undergo metabolic alterations such as the Warburg effect. A method of tracing this key metabolite 2OG at the cellular level is highly desirable. In order to visualize and monitor 2-oxoglutarate metabolism in single living cells, we developed a novel sensor by inserting the functional 2OG-binding domain GAF of the NifA protein into YFP. This sensor was found to be highly specific to 2OG. Following binding of 2OG, fluorescence intensity of the sensor increased with increasing 2OG concentration and reached a 1.5-fold maximum fluorescence signal change (F/F0-1), kinetics of fluorescence signal upon 2OG association with sensor was fast, the dynamic response range of the mOGsor sensors was 100 uM-100 mM. Dissociation between sensor and 2OG was verified both in vitro and in vivo. This sensor reported cellular 2OG dynamics in E. coli cells in real time upon different nutrition challenges and manifested the differences in 2OG pool accumulation and consumption rate. PMID- 24240164 TI - Electrochemiluminescence of luminol enhanced by the synergetic catalysis of hemin and silver nanoparticles for sensitive protein detection. AB - A novel and ultrasensitive electrochemiluminescence (ECL) immunosensor, which was based on the amplifying ECL of luminol by hemin-reduced graphene oxide (hemin rGO) and Ag nanoparticles (AgNPs) decorated reduced graphene oxide (Ag-rGO), was constructed for the detection of carcinoembryonic antigen (CEA). For this proposed sandwich-type ECL immunosensor, Au nanoparticles electrodeposited (DpAu) onto hemin-rGO (DpAu/hemin-rGO) constructed the base of the immunosensor. DpAu had outstanding electrical conductivity to promote the electron transfer at the electrode interface and had good biocompatibility to load large amounts of primary antibody (Ab1), which provided an excellent platform for this immunosensor. Moreover, AgNPs and glucose oxidase (GOD) functionalized graphene labeled secondary antibody (Ag-rGO-Ab2-GOD) was designed as the signal probe for the sandwiched immunosensor. Not only did the hemin-rGO improve the electron transfer of the electrode surface, but hemin also further amplified the ECL signal of luminol in the presence of hydrogen peroxide (H2O2). With the aid of Ag rGO-Ab2-GOD, enhanced signal was obtained by in situ generation of H2O2 and catalysis of AgNPs to ECL reaction of the luminol-H2O2 system. The as-prepared ECL immunosensor exhibited excellent analytical property for the detection of CEA in the range from 0.1 pg mL(-1) to 160 ng mL(-1) with a detection limit of 0.03 pg mL(-1) (SN(-1)=3). PMID- 24240165 TI - Studies on visual detection and surface modification testing of glass microfiber filter paper based biosensor. AB - Glass microfibers are commonly used as biomolecule adsorption media, as structural or disposable components of the optical biosensors. While any improvement in these components are appreciated, utilizing basic tools of traditional approaches may lead to original sensor opportunities as simple, functional designs that can be easily disseminated. Following this pursuit, surface modification of glass microfiber paper surface was performed by 3 aminopropyltriethoxysilane (APTES) and resulting improvement in the cell entrapment capacity could be observed visually, only after Gram staining. Gram staining offered rapid validation of enhanced binding on the glass surface. The same APTES-modified samples were also tested for binding of complementary DNA sequences and the results were less straightforward due to the necessity of DNA visualization by using a fluorescent stain, YOYO-1. Accordingly, when there were no surface modification, DNA and YOYO-1 adsorbed readily on the glass microfiber filter paper, and prolonged the interaction between DNA and YOYO-1. YOYO-1 adsorption on glass could be recognized from the color profile of YOYO-1 emission. This phenomenon can be used to examine suitability of APTES coverage on glass surfaces since YOYO-1 emission can be distinguished by its glass adsorbed versus DNA-bound forms. Aptness of surface coverage is vital to biosensor studies in the sense that it is preceding the forthcoming surface modifications and its precision is imperative for attaining the anticipated interaction kinetics of the surface-immobilized species. The proposed testing scheme offered in this study secures the work, which is aimed to be carried out utilizing such sensing systems and device components. PMID- 24240166 TI - Label-free DNA detection using two-dimensional periodic relief grating as a visualized platform for diagnosis of breast cancer recurrence after surgery. AB - In this study we fabricated a nanopillar array of silicon oxide, involving very large-scale integration (VLSI) and reactive ion etching (RIE), as two-dimensional periodic relief gratings (2DPRGs) on Si surfaces. Thiolated oligonucleotide was successively immobilized on the thiol functionalized surfaces of 2DPRGs by disulfide bond as an optical probe to detect a human genomic DNA (hgDNA584), related to breast cancer recurrence after surgery, from a biological specimen. The oligonucleotide-bound 2DPRG alone produces insignificant structure change, but upon hybridization with hgDNA584 leads to a dramatic change of the pillar scale due to hgDNA584 filling inside the 2DPRG layers. The performance of the sensor was evaluated by capturing hgDNA584 on the oligonucleotide-bound 2DPRGs and measuring the effective refractive index (neff), resulting of color change from pure blue to red, observed by naked eyes along an incident angle of 20-30 degrees . The surface-bound 2DPRG based assay with the chemoresponsive diffraction grating signal transduction scheme results in an experimentally simple DNA detection protocol, displaying attributes of both detection methodologies: the high sensitivity and selectivity afforded by 2DPRG probes and the experimental simplicity, and miniaturization potential provided by the diffraction-based sensing technology. PMID- 24240167 TI - Label-free fluorescence assay for thrombin based on unmodified quantum dots. AB - Rapid and sensitive assay of thrombin and its inhibition in a high-throughput manner is of great significance in the diagnostic and pharmaceutical fields. In this article, we developed a novel biosensor for the detection of thrombin and its inhibition based on the aggregation behavior of the unmodified CdTe QDs. A cationic substrate peptide of thrombin (GGLVPRGSCC-NH2, S-peptide) can attach to the surface of CdTe QDs, partly balance their surface negative charge, and induce the aggregation of QDs, which results in the fluorescence quenching of QDs. After hydrolysis of S-peptide by thrombin, two kinds of shorter peptides (P1-peptide, GGLVPR, and P2-peptide, GSCC) are produced. The uncharged P2-peptide rather than the cationic P1-peptide would bind to QDs. Hence, the CdTe QDs were kept stable in the solution with the fluorescence being maintained. The change of fluorescence intensity would sensitively respond to thrombin activity and its inhibition. Fluorescence spectroscopy, transmission electron microscopy and dynamic light scattering were performed to discuss the quenching mechanism. Under optimized conditions, this method enables measurement of thrombin in the range of 10-100 MUU/mL with the detection limit of 1.5 MUU/mL. Not only in buffer, but also in blood serum, such sensor exhibited extraordinarily high sensitivity and excellent specificity. In addition, the typical inhibitor of thrombin, hirudin, was also successfully assayed by this method (from 2 MUU/mL to 30 MUU/mL with the LOD of 0.21 MUU/mL). Furthermore, the present approach could also be potentially extended to other proteases and their inhibitors detection with unmodified CdTe QDs. PMID- 24240168 TI - Chemiluminescence resonance energy transfer biosensing platform for site-specific determination of DNA methylation and assay of DNA methyltransferase activity using exonuclease III-assisted target recycling amplification. AB - Site-specific determination of DNA methylation and assay of MTase activity can be used for determining specific cancer types, providing insights into the mechanism of gene repression, and developing novel drugs to treat methylation-related diseases. Herein, we develop a simple and highly sensitive chemiluminescence (CL) biosensing platform for site-specific determination of DNA methylation using Exonuclease III (Exo III)-assisted target recycling signal amplification. After bisulfite treatment of mixture of methylated DNA and unmethylated DNA, methylated DNA can hybridize with fluorescein (FAM)-labeled probe DNA to form double stranded DNA (dsDNA), removing the FAM-labeled probe DNA from the surface of grapheme oxide, and the chemiluminescence resonance energy transfer (CRET) sensing signal can be observed and then amplified using Exo III-based recycling strategy. The biosensing platform exhibits excellent high sensitivity, and it can ever distinguish as low as 0.002% methylation level from the mixture, which is superior to most currently reported methods used for DNA methylation assay. In addition, the proposed method can also be used to sensitively assay MTase activity with determination limit of 0.007 U/mL. This CL biosensing offers the advantages of being facile, sensitive, rapid and cost-effective. These features make the system promising for future use for early cancer diagnosis and discover of new anticancer drugs. PMID- 24240169 TI - KMT2D maintains neoplastic cell proliferation and global histone H3 lysine 4 monomethylation. AB - KMT2D (lysine (K)-specific methyltransferase 2D), formerly named MLL2 (myeloid/lymphoid or mixed-lineage leukemia 2, also known as ALR/MLL4), is a histone methyltransferase that plays an important role in regulating gene transcription. In particular, it targets histone H3 lysine 4 (H3K4), whose methylations serve as a gene activation mark. Recently, KMT2D has emerged as one of the most frequently mutated genes in a variety of cancers and in other human diseases, including lymphoma, medulloblastoma, gastric cancer, and Kabuki syndrome. Mutations in KMT2D identified thus far point to its loss-of-function in pathogenesis and suggest its role as a tumor suppressor in various tissues. To determine the effect of a KMT2D deficiency on neoplastic cells, we used homologous recombination- and nuclease-mediated gene editing approaches to generate a panel of isogenic colorectal and medulloblastoma cancer cell lines that differ with respect to their endogenous KMT2D status. We found that a KMT2D deficiency resulted in attenuated cancer cell proliferation and defective cell migration. Analysis of histone H3 modifications revealed that KMT2D was essential for maintaining the level of global H3K4 monomethylation and that its enzymatic SET domain was directly responsible for this function. Furthermore, we found that a majority of KMT2D binding sites are located in regions of potential enhancer elements. Together, these findings revealed the role of KMT2D in regulating enhancer elements in human cells and shed light on the tumorigenic role of its deficiency. Our study supports that KMT2D has distinct roles in neoplastic cells, as opposed to normal cells, and that inhibiting KMT2D may be a viable strategy for cancer therapeutics. PMID- 24240170 TI - A cathepsin B inhibitor, E-64, improves the preimplantation development of bovine somatic cell nuclear transfer embryos. AB - Bovine somatic cell nuclear transfer (SCNT) is an important and powerful tool for basic research and biomedical and agricultural applications, however, the efficiency of SCNT has remained extremely low. In this study, we investigated the effects of cathepsin B inhibitor (E-64) supplementation of culture medium on in vitro development of bovine SCNT embryos. We initially used three concentrations of E-64 (0.1, 0.5, 1.0 MUm), among which 0.5 MUm resulted in the highest rate of blastocysts production after in vitro fertilization (IVF), and was therefore used for further experiments. Blastocyst development of SCNT embryos in the E-64 treatment group also increased relative to the control. Moreover, the cryosurvival rates of IVF and SCNT blastocysts were increased in E-64 treatment groups when compared with the control. On the other hand, we found that IVF and SCNT blastocysts derived from E-64-treated groups had increased total cell numbers and decreased apoptotic nuclei. Furthermore, assessment of the expression of apoptosis-related genes (Bax and Bcl-xL) in bovine IVF and SCNT blastocysts treated with E-64 by real-time RT-PCR analysis revealed suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-xL. Taken together, these finding indicate that addition of E-64 to embryo culture medium may have important implications for improving developmental competence and preimplantation quality in bovine IVF and SCNT embryos. PMID- 24240171 TI - Kar3Vik1 mechanochemistry is inhibited by mutation or deletion of the C terminus of the Vik1 subunit. AB - Force production by kinesins has been linked to structural rearrangements of the N and C termini of their motor domain upon nucleotide binding. In recent crystal structures, the Kar3-associated protein Vik1 shows unexpected homology to these conformational states even though it lacks a nucleotide-binding site. This conservation infers a degree of commonality in the function of the N- and C terminal regions during the mechanochemical cycle of all kinesins and kinesin related proteins. We tested this inference by examining the functional effects on Kar3Vik1 of mutating or deleting residues in Vik1 that are involved in stabilizing the C terminus against the core and N terminus of the Vik1 motor homology domain (MHD). Point mutations at two moderately conserved residues near the Vik1 C terminus impaired microtubule gliding and microtubule-stimulated ATP turnover by Kar3Vik1. Deletion of the seven C-terminal residues inhibited Kar3Vik1 motility much more drastically. Interestingly, none of the point mutants seemed to perturb the ability of Kar3Vik1 to bind microtubules, whereas the C terminal truncation mutant did. Molecular dynamics simulations of these C terminal mutants showed distinct root mean square fluctuations in the N-terminal region of the Vik1 MHD that connects it to Kar3. Here, the degree of motion in the N-terminal portion of Vik1 highly correlated with that in the C terminus. These observations suggest that the N and C termini of the Vik1 MHD form a discrete folding motif that is part of a communication pathway to the nucleotide binding site of Kar3. PMID- 24240173 TI - Chemical force microscopy of stimuli-responsive adhesive copolymers. AB - Atomic force microscopy with chemically sensitive tips was used to investigate the hydrophobic and electrostatic interaction forces of a stimuli-responsive adhesive polymer, and their dynamic changes in response to water immersion and salt concentration. Block copolymer-filled coatings were obtained by incorporating an amphiphilic block copolymer containing a polydimethylsiloxane (PDMS) block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a PDMS matrix. Topographic images of fresh samples revealed the presence of nanoscale domains associated with the presence of copolymers, covered by a thin layer of PDMS. Prolonged (30 days) immersion in aqueous solution led to the exposure of the hydrophilic PDMAEMA chains on the surface. Using adhesion force mapping with hydrophobic tips, we showed that fresh samples were uniformly hydrophobic, while aged samples exhibited lower surface hydrophobicity and featured nanoscale hydrophilic copolymer domains. Force mapping with negatively charged tips revealed remarkable salt-dependent force plateau signatures reflecting desorption of polyelectrolyte copolymer chains. These nanoscale experiments show how solvent-induced conformational changes of stimuli-responsive copolymers can be used to modulate surface adhesion. PMID- 24240172 TI - IkappaB kinase gamma/nuclear factor-kappaB-essential modulator (IKKgamma/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKKbeta in response to transforming growth factor (TGF)-beta1. AB - Transforming growth factor (TGF)-beta1 plays several roles in a variety of cellular functions. TGF-beta1 transmits its signal through Smad transcription factor-dependent and -independent pathways. It was reported that TGF-beta1 activates NF-kappaB and RhoA, and RhoA activates NF-kappaB in several kinds of cells in a Smad-independent pathway. However, the activation molecular mechanism of NF-kappaB by RhoA upon TGF-beta1 has not been clearly elucidated. We observed that RhoA-GTP level was increased by TGF-beta1 in RAW264.7 cells. RhoA-GDP and RhoGDI were bound to N- and C-terminal domains of IKKgamma, respectively. Purified IKKgamma facilitated GTP binding to RhoA complexed with RhoGDI. Furthermore, Dbs, a guanine nucletotide exchange factor of RhoA much more enhanced GTP binding to RhoA complexed with RhoGDI in the presence of IKKgamma. Indeed, si-IKKgamma abolished RhoA activation in response to TGF-beta1 in cells. However, TGF-beta1 stimulated the release of RhoA-GTP from IKKgamma and Rho associated kinase (ROCK), an active RhoA effector protein, directly phosphorylated IKKbeta in vitro, whereas TGF-beta1-activated kinase 1 activated RhoA upon TGF-beta1 stimulation. Taken together, our data indicate that IKKgamma facilitates RhoA activation via a guanine nucletotide exchange factor, which in turn activates ROCK to phosphorylate IKKbeta, leading to NF-kappaB activation that induced the chemokine expression and cell migration upon TGF-beta1. PMID- 24240174 TI - Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis. AB - The histone deacetylases HDAC1 and HDAC2 remove acetyl moieties from lysine residues of histones and other proteins and are important regulators of gene expression. By deleting different combinations of Hdac1 and Hdac2 alleles in the epidermis, we reveal a dosage-dependent effect of HDAC1/HDAC2 activity on epidermal proliferation and differentiation. Conditional ablation of either HDAC1 or HDAC2 in the epidermis leads to no obvious phenotype due to compensation by the upregulated paralogue. Strikingly, deletion of a single Hdac2 allele in HDAC1 knockout mice results in severe epidermal defects, including alopecia, hyperkeratosis, hyperproliferation and spontaneous tumour formation. These mice display impaired Sin3A co-repressor complex function, increased levels of c-Myc protein, p53 expression and apoptosis in hair follicles (HFs) and misregulation of HF bulge stem cells. Surprisingly, ablation of HDAC1 but not HDAC2 in a skin tumour model leads to accelerated tumour development. Our data reveal a crucial function of HDAC1/HDAC2 in the control of lineage specificity and a novel role of HDAC1 as a tumour suppressor in the epidermis. PMID- 24240176 TI - Temporal trends in oral intake ability 3 months after acute ischaemic stroke: analysis of a single-centre database from 2003 to 2011. AB - OBJECTIVE: To analyse the 9-year trend in oral intake ability 3 months after onset in acute stroke patients, with a view to indirect clarification of advances in acute stroke treatment and swallowing rehabilitation. METHODS: A database of patients admitted to our hospital (Saiseikai Kumamoto Hospital, Kumamoto) with acute ischaemic stroke between 2003 and 2011 was analysed. Exclusion criteria were: patients with premorbid modified Rankin Scale score >= 1; those who died during hospital stay; and those whose outcomes after 3 months were not recorded. Mode of nutritional intake was investigated with a questionnaire posted to the patient 3 months after stroke onset. Patients were divided into 2 groups according to mode of nutritional intake: an oral intake group and a non-oral intake group. Whether the date or year of admission were related to the proportion of patients with oral intake, independent of other factors, was investigated using a logistic regression model. RESULTS: Of a total of 2,913 patients, 2,677 (91.9%) were included in the oral intake group. The proportion of patients with oral intake 3 months after stroke increased significantly over the period of analysis (p = 0.034 by Cochran-Armitage test). On logistic regression analysis, the trend was significant after adjustment for age, sex, vascular risk factors, stroke subtype, and stroke severity on admission (odds ratio 1.098, 95% confidence interval 1.029-1.173; per 1 year). CONCLUSION: The proportion of ischaemic stroke patients in the institution studied who were capable of oral intake at 3 months post-stroke increased significantly over the past decade, independent of other patient characteristics. PMID- 24240175 TI - Transcriptome sequencing during mouse brain development identifies long non coding RNAs functionally involved in neurogenic commitment. AB - Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here, we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival, indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem-cell commitment during neurogenesis. PMID- 24240178 TI - An update on clinical trials of targeted therapies in thyroid cancer. AB - PURPOSE OF REVIEW: Several new targeted therapies with multikinase inhibitors targeting vascular endothelial growth factor (VEGF), rearranged during transfection and v-raf murine sarcoma viral oncogene homolog B1 pathways have been tested in clinical trials for radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in the past 10 years. RECENT FINDINGS: Results of the first phase III trial of VEGF-targeted therapy (sorafenib) in DTC were presented in June 2013, and two phase III trials with VEGF and rearranged during transfection-targeted therapies (vandetanib and cabozantinib) in MTC have led to approval by US Food and Drug Administration in the past 2 years. Whereas such therapies increase median progression-free survival compared to placebo, there is no therapy proven to improve overall survival yet. Significant potential adverse event risks associated with such therapies need to be recognized. Dissemination of knowledge about targeted therapies is critical for various medical specialists as patient care for thyroid cancers is best delivered in a multidisciplinary setting. SUMMARY: Successful development of targeted systemic therapies in DTC and MTC in the past 5 years is incredibly exciting in the field and patients with advanced DTC/MTC now have new standard-of-care therapy options. PMID- 24240177 TI - To be, or not to be: functional dilemma of p53 metabolic regulation. AB - PURPOSE OF REVIEW: In recent years, the emerging role of p53 in metabolic regulation has been a topic of great interest. Although apoptotic and growth arrest functions of p53 remain as important mechanisms for preserving genomic stability, metabolic functions of p53 show increasing potential in contributing to p53-mediated tumor suppression. Numerous recent studies provided further insights into the metabolic functions of p53 and their implications in tumorigenesis. RECENT FINDINGS: Several novel p53 metabolic targets have been identified that participate in various aspects of metabolism. Although some studies demonstrate the potential tumor suppressive function of p53 metabolic genes, others reveal prosurvival roles of those targets in both tumor and normal cells. Specifically, Tp53-induced glycolysis and apoptosis regulator (TIGAR) has been thought to promote tumor suppression through metabolic fine-tuning, yet, TIGAR-deficient mice display reduction in tumorigenesis. Finally, characterization of the 3KR mouse model underscored the significance of p53 metabolic regulation in tumor suppression, while also alluding to the potential mechanism for selective regulation of p53 metabolic targets. SUMMARY: Expression of many p53 metabolic genes elicits both antitumor and tumorigenic effects, suggesting that p53 may contribute to cellular protection as well as tumor suppression. Future studies must carefully dissect the duality of p53 metabolic function, which may potentially prove useful in designing cancer therapies. PMID- 24240179 TI - How to use molecular testing results to guide surgery: a surgeon's perspective. AB - PURPOSE OF REVIEW: Multiple genetic mutations have been found to be associated with thyroid cancer, and molecular testing of thyroid nodule fine-needle aspiration (FNA) specimens has been proposed as an adjunct to the cytologic diagnosis. The purpose of this review is to examine how molecular testing of FNAs could be used to guide surgical decision-making. RECENT FINDINGS: B-type RAF kinase mutations in papillary thyroid cancer have been found to be associated with extrathyroidal extension, lymph node metastases, and advanced stage in two meta-analyses that are based largely on retrospective data. Testing for a panel of gene mutations has been found to have high specificity and positive predictive value, whereas microarray testing using a commercially available gene-expression classifier has been found to have high sensitivity and negative predictive value for the diagnosis of malignancy in cytologically indeterminate FNAs. Although there is no consensus regarding the use of such tests, they have already started to change clinical practice. SUMMARY: Molecular testing of FNA specimens may help to avoid diagnostic thyroidectomy or may help in deciding the extent of surgery in a patient with an indeterminate FNA biopsy. The use of these tests is currently undergoing review by a task force within the American Thyroid Association. PMID- 24240180 TI - Anoxic bio-electrochemical system for treatment of complex chemical wastewater with simultaneous bioelectricity generation. AB - Bioelectrochemical treatment system (BET) with anoxic anodic microenvironment was studied with chemical wastewater (CW) in comparison with anoxic treatment (AxT, sequencing batch reactor (SBR)) with same parent anaerobic consortia. BET system documented relatively higher treatment efficiency at higher organic load (5.0 kg COD/m(3)) accounting for COD removal efficiency of (90%) along with nitrate (48%), phosphate (51%), sulphates (68%), colour (63%) and turbidity (90%) removal, compared to AxT operation (COD, 47%; nitrate, 36%; phosphate, 32%; sulphate, 35%; colour, 45% and turbidity, 54%). The self-induced bio-potential developed due to the electrode assembly in BET resulted in effective treatment with simultaneous bioelectricity generation (631 mA/m(2)). AxT operation showed persistent reduction behaviour, while simultaneous redox behaviour was observed with BET indicating balanced electron transfer. BET operation illustrated higher wastewater toxicity reduction compared to the AxT system which documents the variation in bio-electrocatalytic behaviour of same consortia under different microenvironment. PMID- 24240181 TI - Dark fermentation from real solid waste. Evolution of microbial community. AB - The purpose of this paper was to study the evolution of microbial community and its relation to the hydrogen production (HP) steps in thermophilic-dry dark fermentation from real organic fraction of municipal solid waste (OFMSW). Nine organic loading rates (OLRs) (from 9 to 220 g TVS/l/d) were investigated. Population dynamics study showed that increasing OLR (between 9 and 110 g TVS/l/d) resulted in an increase in the relations between Eubacteria:Archaea and hydrolytic-acidogenic bacteria (HABs):acetogens. This was strongly influenced by the microbial content of the OFMSW. The presence of acetogens and Archaea was due to contribution of these microorganisms in the substrate (the biogas produced was methane-free). The maximum value of hydrolysis (63+/-7%) was observed at 110 g TVS/l/d OLR according to maximum HP and HAB activity. The highest average values of acidification yields (57-60%) were achieved for OLR between 28 and 43 g TVS/l/d. PMID- 24240182 TI - Acid hydrolysis of Curcuma longa residue for ethanol and lactic acid fermentation. AB - This research examines the acid hydrolysis of Curcuma longa waste, to obtain the hydrolysate containing lactic acid and ethanol fermentative sugars. A central composite design for describing regression equations of variables was used. The selected optimum condition was 4.91% sulphuric acid, 122.68 degrees C and 50 min using the desirability function under the following conditions: the maximum reducing sugar (RS) yield is within the limited range of the 5 hydroxymethylfurfural (HMF) and furfural concentrations. Under the condition, the obtained solution contained 144 g RS/L, 0.79 g furfural/L and 2.59 g HMF/L and was directly fermented without a detoxification step. The maximum product concentration, average productivity, RS conversion and product yield were 115.36 g/L, 2.88 g/L/h, 89.43% and 64% for L-lactic acid; 113.92 g/L, 2.59 g/L/h, 88.31% and 63.29% for D-lactic acid; and 55.03 g/L, 1.38 g/L/h, 42.66 and 30.57%, respectively, for ethanol using a 7-L jar fermenter. PMID- 24240183 TI - The anaerobic digestion of biologically and physicochemically pretreated oily wastewater. AB - To enhance the degradation of oily wastewater and its biogas production, a biological-physicochemical pretreatment was introduced prior to the anaerobic digestion system. The digestion thereafter proceeded more efficiently due to the inoculation by oil degrading bacteria (Bacillus). A 2-stage pre-mixing is more effective than directly mixing. The effects on the methane production were also investigated by pre-treatment with ultrasonic (US) treatment, combined with citric acid (CA) addition. US pre-treatment was found to improve the initial methane production, and CA pre-treatment could maintain this improvement during the whole digestion stage. Pre-mixing Bacillus at 9 wt.% inoculation, combined with US for 10 min and a CA concentration of 500 mg/L provided the optimum conditions. The most effective enhancement of methane yield was 1100.46 ml/g VS, exceeding that of the control by 280%. The change of coenobium shape and fatty acid content further proved that such pretreatment of oily wastewater can facilitate digestion. PMID- 24240184 TI - Ammonia triggers neuronal disinhibition and seizures by impairing astrocyte potassium buffering. AB - Ammonia is a ubiquitous waste product of protein metabolism that can accumulate in numerous metabolic disorders, causing neurological dysfunction ranging from cognitive impairment to tremor, ataxia, seizures, coma and death. The brain is especially vulnerable to ammonia as it readily crosses the blood-brain barrier in its gaseous form, NH3, and rapidly saturates its principal removal pathway located in astrocytes. Thus, we wanted to determine how astrocytes contribute to the initial deterioration of neurological functions characteristic of hyperammonemia in vivo. Using a combination of two-photon imaging and electrophysiology in awake head-restrained mice, we show that ammonia rapidly compromises astrocyte potassium buffering, increasing extracellular potassium concentration and overactivating the Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1) in neurons. The consequent depolarization of the neuronal GABA reversal potential (EGABA) selectively impairs cortical inhibitory networks. Genetic deletion of NKCC1 or inhibition of it with the clinically used diuretic bumetanide potently suppresses ammonia-induced neurological dysfunction. We did not observe astrocyte swelling or brain edema in the acute phase, calling into question current concepts regarding the neurotoxic effects of ammonia. Instead, our findings identify failure of potassium buffering in astrocytes as a crucial mechanism in ammonia neurotoxicity and demonstrate the therapeutic potential of blocking this pathway by inhibiting NKCC1. PMID- 24240186 TI - Noise and its reduction in graphene based nanopore devices. AB - Ionic current fluctuations in graphene nanopore devices are a ubiquitous phenomenon and are responsible for degraded spatial and temporal resolution. Here, we descriptively investigate the impact of different substrate materials (Si and quartz) and membrane thicknesses on noise characteristics of graphene nanopore devices. To mitigate the membrane fluctuations and pin-hole defects, a SiNx membrane is transferred onto the substrate and a pore of approximately 70 nm in diameter is perforated prior to the graphene transfer. Comprehensive noise study reveals that the few layer graphene transferred onto the quartz substrate possesses low noise level and higher signal to noise ratio as compared to single layer graphene, without deteriorating the spatial resolution. The findings here point to improvement of graphene based nanopore devices for exciting opportunities in future single-molecule genomic screening devices. PMID- 24240185 TI - Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence. AB - Tumor recurrence represents a major clinical challenge. Our data show that emergent recurrent tumors acquire a phenotype radically different from that of their originating primary tumors. This phenotype allows them to evade a host derived innate immune response elicited by the progression from minimal residual disease (MRD) to actively growing recurrence. Screening for this innate response predicted accurately in which mice recurrence would occur. Premature induction of recurrence resensitized MRD to the primary therapy, suggesting a possible paradigm shift for clinical treatment of dormant disease in which the current expectant approach is replaced with active attempts to uncover MRD before evolution of the escape phenotype is complete. By combining screening with second line treatments targeting innate insensitivity, up to 100% of mice that would have otherwise relapsed were cured. These data may open new avenues for early detection and appropriately timed, highly targeted treatment of tumor recurrence irrespective of tumor type or frontline treatment. PMID- 24240187 TI - Comprehensive phylogenetic diversity of [FeFe]-hydrogenase genes in termite gut microbiota. AB - Phylogenetic diversity of [FeFe]-hydrogenase (HydA) in termite guts was assessed by pyrosequencing PCR amplicons obtained using newly designed primers. Of 8,066 reads, 776 hydA phylotypes, defined with 97% nucleotide sequence identity, were recovered from the gut homogenates of three termite species, Hodotermopsis sjoestedti, Reticulitermes speratus, and Nasutitermes takasagoensis. The phylotype coverage was 92-98%, and the majority shared only low identity with database sequences. It was estimated that 194-745 hydA phylotypes existed in the gut of each termite species. Our results demonstrate that hydA gene diversity in the termite gut microbiota is much higher than previously estimated. PMID- 24240188 TI - H2A.Z depletion impairs proliferation and viability but not DNA double-strand breaks repair in human immortalized and tumoral cell lines. AB - In mammalian cells, DNA double-strand breaks (DSB) can be repaired by 2 main pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). To give access to DNA damage to the repair machinery the chromatin structure needs to be relaxed, and chromatin modifications play major roles in the control of these processes. Among the chromatin modifications, changes in nucleosome composition can influence DNA damage response as observed with the H2A.Z histone variant in yeast. In mammals, p400, an ATPase of the SWI/SNF family able to incorporate H2A.Z in chromatin, was found to be important for histone ubiquitination and BRCA1 recruitment around DSB or for HR in cooperation with Rad51. Recent data with 293T cells showed that mammalian H2A.Z is recruited to DSBs and is important to control DNA resection, therefore participating both in HR and NHEJ. Here we show that depletion of H2A.Z in the osteosarcoma U2OS cell line and in immortalized human fibroblasts does not change parameters of DNA DSB repair while affecting clonogenic ability and cell cycle distribution. In addition, no recruitment of H2A.Z around DSB can be detected in U2OS cells either after local laser irradiation or by chromatin immunoprecipitation. These data suggest that the role of H2A.Z in DSB repair is not ubiquitous in mammals. In addition, given that important cellular parameters, such as cell viability and cell cycle distribution, are more sensitive to H2A.Z depletion than DNA repair, our results underline the difficulty to investigate the role of versatile factors such as H2A.Z. PMID- 24240189 TI - Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell. AB - BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4-CD8- (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocyte progenitor homeostasis and expansion, but negatively regulates differentiation from DN to DP cell. Unexpectedly, conditional deletion of BMPRIA from fetal thymocytes (using the Cre-loxP system and directing excision to hematopoietic lineage cells with the Vav promoter) demonstrated that physiological levels of BMP2/4 signaling directly to thymocytes through BMPRIA are required for normal differentiation and expansion of early fetal DN thymocytes. In contrast, the arrest in early thymocyte progenitor differentiation caused by exogenous BMP4 treatment of thymus explants is induced in part by direct signaling to thymocytes through BMPRIA, and in part by indirect signaling through non-hematopoietic cells. Analysis of the transition from fetal DN to DP cell, both by ex vivo analysis of conditional BMPRIA-deficient thymocytes and by treatment of thymus explants with the BMP4-inhibitor Noggin demonstrated that BMP2/4 signaling is a negative regulator at this stage. We showed that at this stage of fetal T-cell development BMP2/4 signals directly to thymocytes through BMPRIA. PMID- 24240192 TI - Neural nAChRs PET imaging probes. AB - There have been a number of attempts to study PET radioligands for imaging nicotinic acetylcholine receptors (nAChRs) in the human brain, and the most successful tracers found are radioligands for imaging alpha4beta2-nAChRs, which is the main cerebral nAChRs subtype. C-Nicotine and 2-[F]FA have been applied in many studies in humans. However, neither is entirely ideal and efforts have been made to develop radioligands with optimized imaging properties. Only a few reports have been published on radioligands for alpha7-nAChRs imaging, another important cerebral nAChRs subtype. This paper will review the development of PET radioligands for imaging cerebral nAChRs. PMID- 24240191 TI - Different functions of HOPS isoforms in the cell: HOPS shuttling isoform is determined by RIP cleavage system. AB - Hepatocyte odd protein shuttling (HOPS) moves between nucleus and cytoplasm. HOPS overexpression leads to cell cycle arrest in G 0/G 1, and HOPS knockdown causes centrosome alterations, with subsequent abnormal cell division. Recently, we demonstrated that HOPS acts as a functional bridge in NPM-p19(Arf) interactions. Here we show that HOPS is present in 3 different isoforms that play distinct intracellular functions. Although HOPS is a transmembrane ubiquitin, an isoform with intermediate molecular weight is cleaved from the membrane and released into the cytosol, to act as the shuttling protein. We identified a signal peptide peptidase structure in N-terminal membrane-bound HOPS that allows the regulated intramembrane proteolysis (RIP) system to control the relative amounts of the released, shuttling isoform capable of binding NPM. These results argue for distinct, isoform-specific functions of HOPS in the nucleolus, nucleus, and cytoplasm and provide insight into the dynamics of HOPS association with NPM, whose mutation and subsequent delocalization is found in 30% of acute myeloid leukemia patients. PMID- 24240190 TI - Arterial territory-specific phosphorylated retinoblastoma protein species and CDK2 promote differences in the vascular smooth muscle cell response to mitogens. AB - Despite recent advances in medical procedures, cardiovascular disease remains a clinical challenge and the leading cause of mortality in the western world. The condition causes progressive smooth muscle cell (SMC) dedifferentiation, proliferation, and migration that contribute to vascular restenosis. The incidence of disease of the internal mammary artery (IMA), however, is much lower than in nearly all other arteries. The etiology of this IMA disease resistance is not well understood. Here, using paired primary IMA and coronary artery SMCs, serum stimulation, siRNA knockdowns, and verifications in porcine vessels in vivo, we investigate the molecular mechanisms that could account for this increased disease resistance of internal mammary SMCs. We show that the residue specific phosphorylation profile of the retinoblastoma tumor suppressor protein (Rb) appears to differ significantly between IMA and coronary artery SMCs in cultured human cells. We also report that the differential profile of Rb phosphorylation may follow as a consequence of differences in the content of cyclin-dependent kinase 2 (CDK2) and the CDK4 phosphorylation inhibitor p15. Finally, we present evidence that siRNA-mediated CDK2 knockdown alters the profile of Rb phosphorylation in coronary artery SMCs, as well as the proliferative response of these cells to mitogenic stimulation. The intrinsic functional and protein composition specificity of the SMCs population in the coronary artery may contribute to the increased prevalence of restenosis and atherosclerosis in the coronary arteries as compared with the internal mammary arteries. PMID- 24240193 TI - The impact of (18)F-FDG-PET/CT on Merkel cell carcinoma management: a retrospective study of 66 scans from a single institution. AB - PURPOSE: Merkel cell carcinomas (MCC) are neuroendocrine skin tumours frequently responsible for lymph node recurrence and metastatic disease and for which optimal management remains to be defined. The objective of this study was to evaluate the impact of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/computed tomography (CT) on the staging and treatment of MCC patients. MATERIALS AND METHODS: Twenty-three patients with a histologic diagnosis of MCC explored by (18)F-FDG-PET/CT between 2004 and 2012 were retrospectively included in the study. The detection of new lesions and the change in tumour staging and treatment were evaluated. For each patient, the (18)F-FDG-PET/CT results were compared with histological, clinical and imaging data. RESULTS: Sixty-six (18)F FDG-PET/CT scans were performed at initial presentation (n=18), during subsequent monitoring (n=34) or during evaluation of chemotherapy response (n=14). The sensitivity, specificity and positive and negative predictive values of the (18)F FDG-PET/CT were 97, 89, 94 and 94%, respectively. Two false-positive results (lymphadenitis) and one false-negative result (regional metastatic lymph nodes) were accounted for. Lesions not detected clinically or by conventional imaging techniques were found in 44% of the 52 (18)F-FDG-PET/CTs performed at initial presentation and subsequent monitoring, with, respectively, 50 and 41% of scans identifying new lesions. At initial presentation, (18)F-FDG-PET/CT led to a change in tumour staging in 39% of patients. Patient management was modified by (18)F-FDG-PET/CT results in one-third of patients (33% of patients at initial presentation, 32% during subsequent monitoring and 36% during evaluation of chemotherapy response). F-FDG-PET/CT incidentally detected four additional histologically confirmed cancers. CONCLUSION: This retrospective study confirms the important impact of (18)F-FDG-PET/CT on the management of MCC patients. PMID- 24240194 TI - Meta-analysis of (11)C-choline and (18)F-choline PET/CT for management of patients with prostate cancer. AB - The aim of the study was to evaluate the diagnostic accuracy and clinical aspects of (11)C-choline and (18)F-choline PET/computed tomography (CT) in patients with prostate cancer. A meta-analysis of original studies from 1998 to September 2013 that described choline PET/CT scans for prostate cancer was conducted. We assessed the main sites of positive findings and the relationship between positive findings and histology, change of treatment and serum prostate-specific antigen (PSA) response to the changed treatment. A total of 3167 patients from 47 eligible articles were assessed with respect to their findings on choline PET/CT during staging and restaging for biochemical recurrence. We examined 661 patients at staging and 158 patients at restaging for biochemical recurrence after external beam radiotherapy. These patients had positive results in the prostate bed more often than did the 2348 patients with biochemical recurrence after radical prostatectomy (P<0.001, chi(2)-test). On assessing 609 patients, the pooled sensitivity of choline PET/CT for pelvic lymph node metastases was found to be 0.62 [95% confidence interval (CI) 0.51-0.66] and the pooled specificity was found to be 0.92 (95% CI 0.89-0.94). Head-to-head studies of 280 patients showed that more patients had positive findings with choline PET/CT than with bone scanning [127 (45%) vs. 46 (16%), odds ratio 2.8, 95% CI 1.9-4.1, P<0.0005, Wilcoxon rank test]. Choline PET/CT led to a change in treatment in 381 (41%) of 938 patients. The changes yielded complete PSA response in 101 of 404 (25%) patients. (11)C-choline or (18)F-choline PET/CT is useful as the first imaging examination for patients with prostate cancer and biochemical recurrence with PSA levels between 1.0 and 50 ng/ml. PMID- 24240195 TI - Relationship of regional cerebral blood flow and kinetic behaviour of O-(2-(18)F fluoroethyl)-L-tyrosine uptake in cerebral gliomas. AB - OBJECTIVES: O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is an established tracer for brain tumour imaging. (18)F-FET kinetics in gliomas appear to have potential for tumour grading, but the mechanisms remain unclear. The aim of this study was to explore the relationship between regional cerebral blood flow (rCBF) as measured by arterial spin labelling MRI and the kinetic behaviour of (18)F-FET PET in cerebral gliomas. MATERIALS AND METHODS: Twenty patients with cerebral gliomas were investigated using arterial spin labelling MRI and dynamic (18)F-FET PET. Time-activity curves (TACs) of (18)F-FET uptake were analysed in 33 different tumour regions. The slopes of TAC during the early (0-5 min; slopeup) and late phases of tracer uptake (17-50 min; slopedown) were fitted using linear regression lines. In addition, TACs of each lesion were assigned to different curve patterns. Furthermore, we calculated tumour-to-brain ratios of (18)F-FET uptake. The relationship between (18)F-FET parameters and rCBF was determined. RESULTS: (18)F-FET uptake in the early phase (slopeup) showed a significant correlation with rCBF (r=0.4; P=0.02). In contrast, both slopedown and TAC patterns showed no significant correlation with rCBF. Furthermore, a significant correlation was found between rCBF and tumour-to-brain ratio (r=0.53; P=0.002). CONCLUSION: There is a relationship between rCBF and (18)F-FET uptake in cerebral gliomas in the initial uptake phase, but the kinetic behaviour of (18)F-FET uptake in the late phase is not significantly influenced by rCBF. Thus, the differential kinetic pattern of (18)F-FET uptake in high-grade and low-grade gliomas appears to be determined by factors other than rCBF. PMID- 24240196 TI - Amyloid imaging with (11)C-PIB PET/CT and glucose metabolism with (18)F-FDG PET/CT in a study on cognitive impairment in the clinical setting. AB - OBJECTIVE: The objective of this study was to evaluate the contribution of amyloid imaging with (11)C-Pittsburgh compound B ((11)C-PIB) and of glucose metabolism on F-fluorodeoxyglucose ((18)F-FDG) PET/CT to the study of cognitive impairment in the clinical setting. PATIENTS AND METHODS: Thirty-four patients (15 male, 19 female) were enrolled in the study. They were classified according to their clinically presented symptoms. Six patients had subjective memory complaints, five had nonamnestic mild cognitive impairment (MCI), seven had amnestic MCI, seven had prodromal Alzheimer's disease (AD), five had frontotemporal dementia, two had dementia with Lewy bodies, and two had cortical degeneration. All the scans were conducted to determine the likelihood of AD or to differentiate between AD and other dementia. Static 30-min (11)C-PIB and 15 min (18)F-FDG PET/CT scans were obtained. A visual analysis of images was performed. RESULTS: Three of the six patients with subjective memory complaints had positive (11)C-PIB scans and one of them also had (18)F-FDG hypometabolism. All five nonamnestic MCI patients had normal (11)C-PIB and (18)F-FDG. Four of the seven amnestic MCI patients showed (11)C-PIB cortical retention but only one had positive (18)F-FDG. Positive (11)C-PIB and (18)F-FDG were detected in five of the seven prodromal AD patients. All the five patients with FDT had positive (18)F FDG scans, but only one of the five had (11)C-PIB cortical retention. Both dementia with Lewy bodies and cortical degeneration patients had positive (11)C PIB and (18)F-FDG scans. CONCLUSION: The combined use of (11)C-PIB and (18)F-FDG PET provides relevant information for the clinical management of cognitive impairment. The detection of positive (11)C-PIB cortical retention in patients may be an indicator of the need for further clinical assessment and monitoring. PMID- 24240198 TI - Challenges and new directions in analytical sample preparation. PMID- 24240197 TI - Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Ca(v)1.1 mutation. AB - We studied a two-generation family presenting with conditions that included progressive permanent weakness, myopathic myopathy, exercise-induced contracture before normokalaemic periodic paralysis or, if localized to the tibial anterior muscle group, transient compartment-like syndrome (painful acute oedema with neuronal compression and drop foot). 23Na and 1H magnetic resonance imaging displayed myoplasmic sodium overload, and oedema. We identified a novel familial Ca(v)1.1 calcium channel mutation, R1242G, localized to the third positive charge of the domain IV voltage sensor. Functional expression of R1242G in the muscular dysgenesis mouse cell line GLT revealed a 28% reduced central pore inward current and a -20 mV shift of the steady-state inactivation curve. Both changes may be at least partially explained by an outward omega (gating pore) current at positive potentials. Moreover, this outward omega current of 27.5 nS/nF may cause the reduction of the overshoot by 13 mV and slowing of the upstroke of action potentials by 36% that are associated with muscle hypoexcitability (permanent weakness and myopathic myopathy). In addition to the outward omega current, we identified an inward omega pore current of 95 nS/nF at negative membrane potentials after long depolarizing pulses that shifts the R1242G residue above the omega pore constriction. A simulation reveals that the inward current might depolarize the fibre sufficiently to trigger calcium release in the absence of an action potential and therefore cause an electrically silent depolarization induced muscle contracture. Additionally, evidence of the inward current can be found in 23Na magnetic resonance imaging-detected sodium accumulation and 1H magnetic resonance imaging-detected oedema. We hypothesize that the episodes are normokalaemic because of depolarization-induced compensatory outward potassium flux through both delayed rectifiers and omega pore. We conclude that the position of the R1242G residue before elicitation of the omega current is decisive for its conductance: if the residue is located below the gating pore as in the resting state then outward currents are observed; if the residue is above the gating pore because of depolarization, as in the inactivated state, then inward currents are observed. This study shows for the first time that functional characterization of omega pore currents is possible using a cultured cell line expressing mutant Ca(v)1.1 channels. Likewise, it is the first calcium channel mutation for complicated normokalaemic periodic paralysis. PMID- 24240199 TI - Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study. AB - BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association. OBJECTIVES: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women. In 2008, we followed up the cohort. Here, we evaluated the association between TCDD exposure and bone structure and geometry in adulthood, and considered whether timing of TCDD exposure before achievement of peak bone mass (assumed to occur 2 years after onset of menarche) modified the association. METHODS: Individual TCDD concentration was measured in archived serum collected soon after the explosion. In 2008, 350 women who were <20 years old in 1976 underwent a dual-energy X-ray absorptiometry (DXA) bone scan. Bone mineral density was measured at the lumbar spine and hip, and hip geometry was extracted from hip DXA scans using the hip structural analysis method. RESULTS: Among premenopausal women, TCDD serum levels were associated with some indexes indicating better bone structure in women exposed before peak bone mass (n=219), with stronger associations in those exposed before 5 years of age (n=46). In contrast, among postmenopausal women, TCDD levels were associated with evidence of better bone structure in women exposed after peak bone mass (n=48) than in other women (n=18). CONCLUSIONS: Our current results do not support the hypothesis that postnatal TCDD exposure adversely affects adult bone health. Continued follow-up of women who were youngest at exposure is warranted. Future studies should also focus on those exposed in utero. PMID- 24240200 TI - Insights in dynamic kinome reprogramming as a consequence of MEK inhibition in MLL-rearranged AML. AB - Single kinase-targeted cancer therapies often failed prolonged responses because cancer cells bypass through alternative routes. In this study, high-throughput kinomic and proteomic approaches enabled to identify aberrant activity profiles in mixed lineage leukemia (MLL)-rearranged acute myeloid leukemia (AML) that defined druggable targets. This approach revealed impaired activity of proteins belonging to the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway. Pharmacological druggable MAPK pathway targets tested in primary MLL-rearranged AML included MAPKK1/2 (MEK), cyclic AMP-responsive element binding protein (CREB) and MAPK8/9 (JNK). MEK inhibition showed to severely decrease MLL-rearranged AML cell survival without showing cytotoxicity in normal controls, whereas inhibition of CREB and JNK failed to exhibit MLL selectivity. Exploring the working mechanism of MEK inhibition, we assessed proteome activity in response to MEK inhibition in THP-1. MAPK1/3 (Erk) phosphorylation was instantly decreased in concurrence with a sustained Akt/mammalian target of rapamycin (mTOR) phosphorylation that enabled a subpopulation of cells to survive MEK inhibition. After exhaustion of MEK inhibition the AML cells recovered via increased activity of vascular endothelial growth factor receptor-2 (VEGFR-2) and Erk proteins to resume their proliferative state. Combined MEK and VEGFR-2 inhibition strengthened the reduction in MLL-rearranged AML cell survival by blocking the Akt/mTOR and MAPK pathways simultaneously. The generation of insights in cancerous altered activity profiles and alternative escape mechanisms upon targeted therapy allows the rational design of novel combination strategies. PMID- 24240201 TI - Rapid rate of peripheral blood blast clearance accurately predicts complete remission in acute myeloid leukemia. PMID- 24240202 TI - Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells. AB - MLL-AF4 fusion is hallmark in high-risk infant pro-B-acute lymphoblastic leukemia (pro-B-ALL). Our limited understanding of MLL-AF4-mediated transformation reflects the absence of human models reproducing this leukemia. Hematopoietic stem/progenitor cells (HSPCs) constitute likely targets for transformation. We previously reported that MLL-AF4 enhanced hematopoietic engraftment and clonogenic potential in cord blood (CB)-derived CD34+ HSPCs but was not sufficient for leukemogenesis, suggesting that additional oncogenic lesions are required for MLL-AF4-mediated transformation. MLL-AF4+ pro-B-ALL display enormous levels of FLT3, and occasionally FLT3-activating mutations, thus representing a candidate cooperating event in MLL-AF4+ pro-B-ALL. We have explored whether FLT3.TKD (tyrosine kinase domain) mutation or increased expression of FLT3.WT (wild type) cooperates with MLL-AF4 to immortalize/transform CB-CD34+ HSPCs. In vivo, FLT3.TKD/FLT3.WT alone, or in combination with MLL-AF4, enhances hematopoietic repopulating function of CB-CD34+ HSPCs without impairing migration or hematopoietic differentiation. None of the animals transplanted with MLL AF4+FLT3.TKD/WT-CD34+ HSPCs showed any sign of disease after 16 weeks. In vitro, enforced expression of FLT3.TKD/FLT3.WT conveys a transient overexpansion of MLL AF4-expressing CD34+ HSPCs associated to higher proportion of cycling cells coupled to lower apoptotic levels, but does not augment clonogenic potential nor confer stable replating. Together, FLT3 activation does not suffice to immortalize/transform MLL-AF4-expressing CB-CD34+ HSPCs, suggesting the need of alternative (epi)-genetic cooperating oncogenic lesions. PMID- 24240204 TI - Aesthetic surgery of the buttocks: imaging appearance. AB - Familiarity with the imaging appearance and potential complications of buttocks aesthetic surgery is important for radiologists. In this review, we illustrate the spectrum of imaging features after buttocks implants, liposuction, fat injections and silicone injections. Complications such as fat necrosis, abscess, and silicone migration are also presented. PMID- 24240203 TI - Blocking ETV6/RUNX1-induced MDM2 overexpression by Nutlin-3 reactivates p53 signaling in childhood leukemia. AB - ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia. It is responsible for the initiation of leukemia but also indispensable for disease maintenance and propagation, although its function in these latter processes is less clear. We therefore investigated the effects of the perceived p53 pathway alterations in model cell lines and primary leukemias and, in particular, how E/R upregulates MDM2, the predominant negative regulator of p53. We found that E/R transactivates MDM2 in both p53(+/+) and p53(-/-) HCT116 cells by binding to promoter-inherent RUNX1 motifs, which indicates that this activation occurs in a direct and p53-independent manner. Treatment of E/R positive leukemic cell lines with Nutlin-3, a small molecule that inhibits the MDM2/p53 interaction, arrests their cell cycle and induces apoptosis. These phenomena concur with a p53-induced expression of p21, pro-apoptotic BAX and PUMA, as well as caspase 3 activation and poly ADP-ribose polymerase cleavage. The addition of DNA-damaging and p53-activating chemotherapeutic drugs intensifies apoptosis. Moreover, Nutlin-3 exposure leads to an analogous p53 accumulation and apoptotic surge in E/R-positive primary leukemic cells. Our findings clarify the role of p53 signaling in E/R-positive leukemias and outline the potential basis for its therapeutic exploitation in this setting. PMID- 24240205 TI - MR imaging features of spindle cell lipoma. AB - OBJECTIVE: To assess the MR imaging features of spindle cell lipomas (SCL) and to compare these appearances directly with the histopathological findings. MATERIALS AND METHODS: A retrospective review of our soft tissue tumor database was performed. This yielded 1,327 histologically proven lipomas, of which 25 were confirmed as being SCLs. Fourteen of the 25 patients had MR examinations available for review and only these patients were included in our study. Lesions were assessed at MR examination for the degree of internal fat signal content with grade 0 representing 0 % fat signal and grade 4 100 % fat signal. The degree of fat suppression and contrast-enhancement pattern were also recorded. The excision specimens were independently reviewed by a consultant histopathologist. The histology specimens were assessed for the amount of internal fat and non adipose tissue and graded using the same scale applied for the imaging. Where core needle biopsy (CNB) was performed, the CNB specimens were also examined for positive features of SCL. RESULTS: In our study, 93 % (13/14) of our patients were male and the average age was 58 years. 65 % (9/14) of the lesions presented in the upper back, shoulder, or neck. All lesions were subcutaneous. 35 % (5/14) of the SCLs demonstrated grade 3 (>75 %) or grade 4 (100 %) fat signal on MR examination. 35 % (5/14) of the lesions had grade 2 (25-75 %) fat signal and 29 % (4/14) of the lesions demonstrated grade 0 (0 %) or grade 1 (<25 %) fat signal. 43 % (6/14) of lesions demonstrated homogenous fat suppression, 28 % (4/14) showed focal areas of high internal signal, and 28 % (4/14) had diffuse internal high signal on fluid-sensitive fat-saturated sequences. 86 % (6/7) of the cases demonstrated septal/nodular enhancement. The diagnosis was evident on the CNB specimen in 100 % (9/9) cases. The histopathology fat content grade was in agreement with the imaging grade in 86 % (12/14) cases. CONCLUSIONS: The internal signal pattern of SCL can range broadly, with low fat content lesions seen almost as commonly as intermediate and high fat content lesions. We also found that the fat:non-fat internal MR signal pattern of these lesions is accurately reflected in their composition at histology. PMID- 24240206 TI - Pollen selection for low temperature adaptation in tomato. AB - Pollen selection experiments were conducted in tomato to determine the effects of low temperature conditions during pollination on the rate of root elongation of the progeny. Pollen was harvested from an F1 interspecific hybrid between a high altitude Lycopersicon hirsutum accession and the cultivated tomato L. esculentum. The pollen was applied to stigmas of malesterile L. esculentum plants maintained in growth chambers set at either 12 degrees C/7 degrees C or 24 degrees C/18 degrees C. BC1 seeds from the low and normal temperature crosses were germinated and root elongation rate was measured at either 9 degrees C or 24 degrees C. At 9 degrees C, the rate of root elongation for progeny of the low temperature crosses was higher than for progeny of crosses at normal temperatures; at 24 degrees C the rate of root elongation was similar for the two crossing treatments. To compare the temperature responses of the two backcross populations we also calculated the relative inhibitory effect of low temperature on the rate of root elongation: the ratio between the rate of root elongation at 9 degrees C to that at 24 degrees C. Root elongation of seedlings from the low temperature crosses was less inhibited by the cold than root elongation for progeny of the normal temperature crosses. These results suggest a relationship between pollen selection at low temperatures and the expression of a sporophytic trait under the same environmental stress. PMID- 24240207 TI - A note on the effect of observations with missing data on genetic correlation estimates. AB - Various studies have estimated covariance components as half the difference between the variance component of the sum of the variable values, for each observation, and the sum of the corresponding variable variance components. Although the variance components for the separate variables can be computed using all available data, the variance components of the sum can be computed only from those observations with records for both variables. Previous studies have suggested eliminating observations with missing data, because of possible selection bias. The effect of missing data on estimates of covariance components and genetic correlations was tested on sample beef cattle data and simulated data by randomly deleting differing proportions of records of one variable for each pair of variables analyzed. Estimates of genetic correlations computed with observations with missing data eliminated, were more accurate than estimates computed using all available data. Furthermore, when observations with missing data were included, estimates of genetic correlation far outside the parameter space were common. Therefore, this method should be used only if observations with missing data have been eliminated. PMID- 24240208 TI - Genetics of the polycross : 2. Male fertility variation in norway spruce, Picea abies (L.) Karst. AB - Seeds from polycrosses with Norway spruce, in which the same sixteen male parents were crossed to a number of female parents in each of two years, were analysed electrophoretically to detect departures from male gamete frequencies expected assuming equal male fertilities, and to detect heterogeneity among female parents in male gamete frequencies in seeds. The data were also used to estimate the fertilities of the polycross trees used as male parents. Significant departures from male gamete frequencies expected assuming equal male fertilities were found in the seed pooled from all crosses. Male fertilities estimated from male gamete frequencies in seed from all crosses also departed significantly from expectation. The results are discussed with respect to assumptions made when estimating general combining abilities and expected response to selection in polycrosses. PMID- 24240209 TI - Allozyme variation in rye, Secale cereale L. : 2. Commercial varieties. AB - Eleven samples of eight European commercial varieties of winter rye were examined at eight polymorphic enzyme loci. Genotype frequencies fitted Hardy-Weinberg expectations at all loci in all samples studied. Of the total genetic diversity recorded at the 8 loci, only 7% was expressed between varieties. Allele frequency differences between varieties were, however, sufficient to allow a characterization of each variety by a specific set of allele frequencies. Using subsets of the original data, it could be demonstrated that all pairs of varieties but one still showed significant allozyme differences, when only 4 loci were screened in samples half the original size of 200 individuals. Even when only one locus was analyzed, all varieties but two were distinguishable, but this "diagnostic" locus was not identical in all pairwise comparisons. PMID- 24240210 TI - Genetic and non-genetic factors affecting anther culture of Brussels sprouts (Brassica oleracea var. gemmifera). AB - Eight inbred lines of Brussels sprouts and ten F1 hybrids derived from them were tested for their response to anther culture. From 5-19 plants per genotype were tested, and each plant was tested on 3-6 separate occasions. Results from the inbred lines were broadly similar to those from the F1 hybrids, despite the inbreds producing fewer buds and having a higher frequency of anther deformities. The maximum embryo yield from an inbred line was 215 embryos per 100 anthers, and from a hybrid was 275. From estimation of the variance components it was calculated that, for both inbreds and hybrids, about half the total variation was genetic whereas variation due to plants within genotypes and to occasions within plants were each about 13% of the total. The narrow sense heritability of responsiveness to anther culture (estimated by the proportion of variation between inbred lines which was genetic) was 0.48, and there was partial dominance for this character. In three cases the hybrid outyielded the better inbred, and this heterosis may well be due to dispersed dominant genes. PMID- 24240211 TI - A theoretical model for quantitatively inherited traits influenced by nuclear cytoplasmic interactions. AB - Cytoplasmic genes of crop species exhibit non-Mendelian inheritance and affect quantitative traits such as biomass and grain yield. Photosynthesis and respiration are physiological processes responsible, in part, for the expression of such quantitative traits and are regulated by enzymes encoded in both the cytoplasm and nucleus. Cytoplasmic genes are located in the chloroplast and mitochondrial genomes. Unlike the nuclear genome, the cytoplasmic genomes consist of single, circular, double-stranded molecules of DNA, and in many crop species, the cytoplasmic genomes are inherited solely through the maternal parent. Maternal inheritance of cytoplasmic genomes and Mendelian inheritance of the nuclear genome were used to model the genotypic value of an individual. The model then was utilized to derive genetic variances and covariances for a random-mating population. Finally, the use of reciprocal mating designs to estimate variance components was investigated. PMID- 24240212 TI - Mutant gene frequencies in cats of the greater London area. AB - The frequencies of seven mutant genes of the domestic cat have been estimated by sampling the population of greater London, specific areas of the capital and adjoining counties. An attempt was made to diversify the method of sampling by concentrating upon certain categories of cats. In addition to the usual sightings of cats in streets and open spaces, surveys were made of cats attending a veterinary clinic, those staying at a boarding cattery, those exhibited in the household pet classes at a cat show and those in rescue centres. Although there are inconsistencies, the general impression from frequencies in present and earlier observations is that the lighter phenotypes (mackerel tabby, blue dilution and orange) are favoured by human preference, as opposed to the darker phenotypes (blotched tabby, black and non-orange). Reasons are discussed for thinking that, while human preference may be a factor in the evolution of the feline polymorphism, it is not the fundamental cause. PMID- 24240213 TI - Chromosomal location of a K/Na discrimination character in the D genome of wheat. AB - K/Na ratios have been determined in the leaves of salt-treated plants of 14 disomic substitution lines in which each of the D-genome chromosomes replaces the homoeologous A- or B-genome chromosome in the tetraploid wheat variety Langdon (AABB genome). Aneuploid lines of hexaploid bread wheat (cv Chinese Spring) having a reduced or an enhanced complement of chromosome 4D have also been examined. These investigations show that the gene(s) determining K/Na ratios in the leaves of wheat plants grown in the presence of salt is located on the long arm of chromosome 4D. PMID- 24240214 TI - Comparative restriction endonuclease analysis and molecular cloning of plastid DNAs from wild species and cultivated varieties of the genus Beta (L.). AB - A phyletic tree of the genus Beta has been constructed based on EcoRI and PstI plastid DNA restriction patterns of eight species from three sections of the genus. In contrast to the remarkable morphological variability of the varieties of B. vulgaris the restriction patterns of the plastid DNA of this species were found to be almost identical. The comparison of plastic DNAs of B. vulgaris crassa fertile and sterile lines with 13 different restriction enzymes revealed only a single fragment polymorphism in the HindIII patterns. Hybridization analyses in the plastidal rDNA region revealed an interesting loss of an EcoRI restriction site in all cultivated B. vulgaris varieties in contrast to wild species. The results of the construction of clone banks for SalI and BamHI fragments of plastid DNA from fertile B. vulgaris crassa are reported and difficulties in the cloning of specific fragments are discussed. PMID- 24240215 TI - Inheritance of resistance to potato y viruses in Phaseolus vulgaris L : 1. Two independent genes for resistance to watermelon mosaic virus-2. AB - Resistance to watermelon mosaic virus-2 in Phaseolus vulgaris L. is conferred by two distinct dominant alleles at independent loci. Based on segregation data one locus is designated Wmv, the other, Hsw. The dominant allele Wmv from cv. Great Northern 1140 prevents systemic spread of the virus but viral replication occurs in inoculated tissue. In contrast, Hsw confers both local and systemic resistance to WMV-2 below 30C. At higher temperatures, plants that carry this allele in the absence of modifying or epistatic factors develop systemic veinal necrosis upon inoculation with the virus that results in rapid death. Patho-type specificity has not been demonstrated for either allele; both factors confer resistance to every isolate tested. A temperature-sensitive shift in epistasis is apparent between dominant alleles at these loci. Because Hsw is very tightly linked if not identical to the following genes for hypersensitivity to potyviruses I, (bean common mosaic virus), Bcm, (blackeye cowpea mosaic virus), Cam, (cowpea aphid borne mosaic virus) and Hss (soybean mosaic virus), parental, reciprocal dihybrid F1 populations, and selected F3 families were inoculated with each of these viruses and held at 35 C. F1 populations developed vascular necrosis completely or primarily limited to inoculated tissue, while F3 families from WMV-2 susceptible segregates were uniformly susceptible to these viruses. The relationship between Hsw, Wmv and other genes for potyvirus resistance suggest patterns in the evolution of resistance and viral pathogenicity. Characterization of the resistance spectrum associated with each factor provides an additional criterion to distinguish genes for plant virus resistance. PMID- 24240216 TI - Fertile revertants from S-type male-sterile maize grown in vitro. AB - Plants were regenerated from callus cultures of maize inbred W182BN with the S(USDA) type of cytoplasmic male sterility (cms). Some regenerates from 16 of 18 separate cultures had fertile tassels. Many other regenerates, whose fertility could not be scored accurately because of abnormal plant morphology, produced fertile progeny after pollination with N cytoplasm W182BN. Revertant plants and/or progeny were obtained from all 18 cultures, which included the CA, D, LBN, and S sources of cmsS. More revertants were recovered from cultures maintained as callus for 12 months than from 3-4 month old cultures. Several types of evidence (absence of segregation for fertility after selfing or pollination of revertants with standard W182BN, pollen viability counts, failure of revertants to restore sterile cmsS lines to fertility, mitochondrial DNA analyses) indicated that the reversion to fertility involved cytoplasmic rather than nuclear alterations. All revertants examined lacked the S1 and S2 plasmid-like DNAs characteristic of the mitochondrial genome of sterile cmsS lines. Most callus cultures lost S1 and S2 after 13-20 months in vitro. No revertants were seen among thousands of W182BN cmsS plants grown from seed in the field or among plants from tissue cultures of W182BN with the C or T types of cms. The cytoplasmic revertants recovered from culture may be useful for the molecular analysis of cmsS. PMID- 24240217 TI - Null alleles for gliadin blocks in bread and durum wheat cultivars. AB - Wheat gliadin proteins are coded by clusters of genes (complex loci) located on the short arms of chromosomes of homoeologous groups 1 and 6 in bread (6x) and durum (4x) wheats. The proteins expressed by the various complex loci have been designated gliadin blocks. In a survey of accessions from the Germplasm Institute (C.N.R., Bari, Italy) collection, several different accessions have been found that lack particular blocks of proteins (null alleles). In some bread wheat accessions, seeds do not express gliadins that are coded by chromosomes 1D and 6A in normal cultivars. Similarly, some durum wheat accessions lack omega-gliadin components coded for by genes on chromosomes 1A and 1B. The missing proteins do not result from the absence of whole chromosomes, but may be the consequence of partial deletion of these genes at a complex locus or result from their silencing. PMID- 24240218 TI - Variability and genetics of spacer DNA sequences between the ribosomal-RNA genes of hexaploid wheat (Triticum aestivum). AB - Using restriction enzyme digests of genomic DNA extracted from the leaves of 25 hexaploid wheat (Triticum aestivum L. em. Thell.) cultivars and their hybrids, restriction fragment length polymorphisms of the spacer DNA which separates the ribosomal-RNA genes have been examined. (From one to three thousand of these genes are borne on chromosomes 1B and 6B of hexaploid wheat). The data show that there are three distinct alleles of the 1B locus, designated Nor-B1a, Nor-B1b, and Nor-B1c, and at least five allelic variants of the 6B locus, designated Nor B2a, Nor-B2b, Nor-B2c, Nor-B2d, and Nor-B2e. A further, previously reported allele on 6B has been named Nor-B2f. Chromosome 5D has only one allelic variant, Nor-D3. Whereas the major spacer variants of the 1B alleles apparently differ by the loss or gain of one or two of the 133 bp sub-repeat units within the spacer DNA, the 6B allelic variants show major differences in their compositions and lengths. This may be related to the greater number of rDNA repeat units at this locus. The practical implications of these differences and their application to wheat breeding are discussed. PMID- 24240219 TI - Effect of population structure on protein-yield improvements in spring wheat (Triticum aestivum L. em Thell). AB - In a study designed to develop a more efficient breeding method for concurrent protein-yield improvements in wheat (Triticum aestivum L. em. Thell), 7 base populations [2 F2's, 1 intermated F2 (IF2) and 4 partial backcross (PBC) populations] developed from biparental crosses involving 2 Canadian hard red spring (CHRS) and 2 Canadian utility (CU) wheat cultivars were evaluated in Winnipeg, Manitoba, Canada. The IF2 and PBC populations were generated for comparison with conventional F2 populations and to determine which of the 4 methods of population development would provide a more efficient means of producing potentially superior genetic recombinants. Parameters pertaining to means, variances, correlations, heritabilities and frequencies of desirable and undesirable progenies were used to evaluate the limitations to genetic gain that may be expected from selection for GY and GPC in F2, IF2, CHRS-PBC and CU-PBC populations. Analysis of protein and yield data from 105 S1 lines derived from each of the 7 populations showed the CU-PBC's to have the highest grain yield (GY) and the lowest grain protein concentration (GPC) means; and the CHRS-PBC's, the lowest GY and the highest GPC means. The F2 and IF2 populations were intermediate for both characteristics. Populations developed from the same biparental cross did not differ significantly with respect to the majority of genetic parameters. However, desirable progenies combining high GY with high GPC were more frequent in the CU-PBC, and least frequent in the CHRS-PBC populations. The observed superiority of the CU-PBC populations appeared to be related to the advantage the system has in preserving the genetic integrity of a proven cultivar, while adding desirable genetic factors from another cultivar, thus capitalizing on introgression and upgrading simultaneously. PMID- 24240220 TI - A genetic analysis of cell culture traits in tomato. AB - Tomato genotypes superior in regenerating plants from protoplast and callus cultures were obtained by transferring regeneration capacity from Lycopersicon peruvianum into L. esculentum by classical breeding. The genetics of regeneration and callus growth have been studied in selfed and backcross progenies of a selected plant (MsK93) which has 25% L. peruvianum in its ancestry. Segregation data showed that the favourable cell culture traits of L. peruvianum are dominant. Regeneration capacity from established callus cultures was controlled by two dominant genes. Callus growth on primary expiants, callus growth of established cultures and shoot regeneration from explants had high heritabilities (0.47, 0.78, 0.87, respectively). Callus growth and regeneration capacity were not correlated within the populations studied. PMID- 24240221 TI - Genetics of fertility restoration in cytoplasmic male sterile Phaseolus vulgaris L. : 1. Cytoplasmic alteration by a nuclear restorer gene. AB - Restoration of fertility in cytoplasmic male sterile Phaseolus vulgaris by line R 351 was controlled by a single gene. The restorer gene (Fr) displayed incomplete dominance leading to partial restoration of fertility in F1 generations; full restoration was not achieved until the F2 generation. Once full restoration of fertility was produced in the F2 generation, no segregation for sterility was observed in subsequent generations derived from heterozygotes Frfr, either by testcrossing (restored * maintainer) or in F3 progenies. Implications of the irreversible nature of this restoration are discussed. PMID- 24240222 TI - Comparison of restriction endonucleases and sources of probes for their efficiency in detecting restriction fragment length polymorphisms in lettuce (Lactuca sativa L.). AB - As a first step in developing a detailed genetic map of lettuce (Lactuca sativa L.), 156 cDNA and 123 genomic DNA clones of lettuce were compared for their efficiency to detect restriction fragment length polymorphism (RFLP) between four lines of lettuce. Polymorphism was detected 2.5 times more frequently with cDNA probes than random genomic probes. Less polymorphism was detected with cDNA clones homologous to single copy than with cDNA clones homologous to multiple copy DNA sequences. A lower percentage of polymorphism was detected with genomic DNA clones homologous to repetitive sequences than with other types of probes. Digests with each of nine restriction endonucleases were compared; increased polymorphism was not correlated with the presence of a CpG dimer in the recognition sequence of the restriction endonuclease. Digests with enzymes recognizing four base pairs, however, displayed RFLPs less frequently. The six pairwise comparisons of the four lettuce lines showed different frequencies of polymorphism which only approximately corresponded to genetic distances obtained from previous isozyme analyses. PMID- 24240223 TI - Heterokaryon formation in the basidiomycete Schizophyllum commune by electrofusion of protoplasts. AB - Conditions for high frequency electrofusion of protoplasts from the basidiomycete Schizophyllum commune are described. Visual inspection revealed up to 30% of the protoplasts engaged in fusion. Using complementing nutritional mutations, nearly 7% of the regenerated protoplasts could be recovered as heterokaryotic mycelia. The method is probably equally applicable to other basidiomycetes such as Agaricus bisporus, permitting the recovery of fusion products in the absence of selection markers. PMID- 24240224 TI - Improving grain yield in backcross populations from Avena sativa * A. sterilis matings by using independent culling for harvest index and vegetative growth index or unit straw weight. AB - Grain yield was selected in Avena sativa X A. sterilis populations of segregates by applying independent culling for harvest index and either vegetative growth index or unit straw weight. Samples of lines intensively selected for harvest index had high harvest index but low grain yield because they had low vigor. Populations intensively selected for growth rate index or unit straw weight had high biological yield but low harvest index. Intensive selection for grain yield per se resulted in samples with high grain yield, but they were late and tall. Samples selected for harvest index at a 25% selection intensity first and subsequently selected for vegetative growth index or unit straw weight had grain yield as high as the samples selected for grain yield per se and vegetative growth index, and they had acceptable heading date and plant height. Backcrosses three and four were best, among the various BC generations, for selecting oat lines with high grain yield and suitable agronomic traits. CI 7463 was superior to CI 8044 as a recurrent parent, and B 445 was inferior to other A. sterilis accessions as a donor parent. PMID- 24240225 TI - Mitochondrial DNA modifications associated with cytoplasmic male sterility in rice. AB - Mitochondrial DNA was isolated from fertile and cytoplasmic male sterile lines of rice. Restriction analysis showed specific modifications in the male sterile cytoplasm. In addition to the major mitochondrial DNA, three small plasmid-like DNA molecules were detected by agarose gel electrophoresis in both cytoplasms. An additional molecule was specifically found in the sterile cytoplasm. These mitochondrial DNA modifications support the hypothesis of the mitochondrial inheritance of the cytoplasmic male sterility in rice. PMID- 24240226 TI - Field performance and cytology of protoplast-derived rice (Oryza sativa): high yield and low degree of variation of four japonica cultivars. AB - Protoplast-derived rice plants of four Japanese cultivars, Nipponbare, Fujisaka 5, Norin 14 and Iwaimochi were individually cultivated in a submerged paddy field. They exhibited more stems, which resulted in more panicles than respective control plants. Other characteristics of protoplast-derived plants were (compared with controls): a slightly shorter or similar culm length, fewer spikelets per panicle, slightly lower seed fertility and similar or lighter 1,000 kernel weight. Grain yield of protoplast-derived plants was more than that of respective control plants in four cultivars. The cause of the higher yield of protoplast derived plants seems to be mainly due to increased panicle number. Among 126 protoplast-derived plants, 1 triploid, 10 tetraploids and 1 aneuploid were found. Furthermore, 11 variants with low seed fertility showing no gross chromosomal anomalies and one plant with abnormal panicles were found. In total, about 80% of protoplastderived plants showed normal characters. The present results are encouraging for the possibility of rice breeding using protoplasts. PMID- 24240227 TI - Erratum. PMID- 24240228 TI - Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-alpha (TNF-alpha) using AZD9773, an anti-TNF-alpha immune Fab, in murine CLP sepsis. AB - OBJECTIVE AND DESIGN: TNF-alpha neutralization is associated with increased mortality in mouse cecal ligation puncture (CLP) models. AZD9773 is an ovine polyclonal human TNF-alpha immune Fab, with pharmacological properties that differ from previously studied anti-TNF-alpha agents. We explored the safety and efficacy of therapeutically administered AZD9773 in mouse CLP sepsis. METHODS: A moderate/severe-grade CLP model resulting in 20-30 % 5-day survival and a mild grade CLP model resulting in ~70 % 5-day survival were established in human TNF alpha transgene/murine TNF null (Tg1278/-/-) mice. TREATMENT: Mice received saline resuscitation and imipenem administration every 12 h (0-72 h post-CLP). AZD9773 (or DigiFab control) was dosed 24, 36, 48 and 60 h post-CLP. RESULTS: Therapeutic dosing of AZD9773 in moderate/severe-grade CLP resulted in significantly increased survival (>70 %) compared with DigiFab (27 %, P < 0.05). Therapeutic dosing of AZD9773 in mild-grade CLP did not significantly affect survival outcome compared with DigiFab or imipenem alone (~60-70 % survival). CONCLUSIONS: These data demonstrate that TNF-alpha neutralization can improve survival in moderate/severe CLP sepsis. TNF-alpha suppression in mild-grade models was not associated with survival benefit and did not increase 5-day mortality. These findings suggest that therapeutic benefit following TNF-alpha attenuation in models of sepsis may depend on model severity. PMID- 24240229 TI - Effect of salicin on gut inflammation and on selected groups of gut microbiota in dextran sodium sulfate induced mouse model of colitis. AB - OBJECTIVE AND DESIGN: This study was undertaken to evaluate the anti-inflammatory effect of the pure compound salicin on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to quantify the major gut bacteria during the treatment. MATERIAL OR SUBJECTS: Experimental colitis was induced in Swiss albino mice by dissolving 2 % DSS in their drinking water for 7 days. Five mice were used in each group. TREATMENT: Salicin (100 and 200 mg per body weight) was administered daily through oral gavage for 7 days. METHODS: Disease activity index (DAI), colon length, myeloperoxidase (MPO) assay, pro-inflammatory cytokine expression, histological changes and absolute number of gut microbiota were measured after treatment. Student's t test was applied for statistical analysis. RESULTS: Salicin significantly attenuated DSS-induced DAI scores, shortening of colon length and tissue MPO activity. Salicin administration also effectively and dose-dependently prevented pro-inflammatory cytokine expression in DSS-induced colitis mice. Histological examination indicated that salicin suppressed edema, mucosal damage and the loss of crypts induced by DSS. Oral administration of salicin in DSS-treated mice prevented loss of gut microbiota during the short period of treatment. CONCLUSIONS: Salicin has an anti-inflammatory effect, and it may have therapeutic value in ameliorating inflammation during colitis. PMID- 24240230 TI - Nanotechnology: emerging tools for biology and medicine. AB - Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine. PMID- 24240232 TI - Heterochromatin establishment at pericentromeres depends on nuclear position. AB - Mammalian development begins with fertilization of an oocyte by the sperm followed by genome-wide epigenetic reprogramming. This involves de novo establishment of chromatin domains, including the formation of pericentric heterochromatin. We dissected the spatiotemporal kinetics of the first acquisition of heterochromatic signatures of pericentromeric chromatin and found that the heterochromatic marks follow a temporal order that depends on a specific nuclear localization. We addressed whether nuclear localization of pericentric chromatin is required for silencing by tethering it to the nuclear periphery and show that this results in defective silencing and impaired development. Our results indicate that reprogramming of pericentromeric heterochromatin is functionally linked to its nuclear localization. PMID- 24240233 TI - A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans. AB - We examined how a p53 enhancer transmits regulatory information in vivo. Using genetic ablation together with digital chromosome conformation capture and fluorescent in situ hybridization, we found that a Drosophila p53 enhancer region (referred to as the p53 response element [p53RE]) physically contacts targets in cis and across the centromere to control stress-responsive transcription at these sites. Furthermore, when placed at ectopic genomic positions, fragments spanning this element re-established chromatin contacts and partially restored target gene regulation to mutants lacking the native p53RE. Therefore, a defined p53 enhancer region is sufficient for long-range chromatin interactions that enable multigenic regulation. PMID- 24240234 TI - Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny. AB - V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome. PMID- 24240231 TI - Building the mammalian testis: origins, differentiation, and assembly of the component cell populations. AB - Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial cells arise from bipotential precursors present in the precursor tissue, the genital ridge. These cell types do not differentiate independently but depend on signals from Sertoli cells that differentiate under the influence of transcription factors SRY and SOX9. While these steps are becoming better understood, the origins and roles of many testicular cell types and structures-including peritubular myoid cells, the tunica albuginea, the arterial and venous blood vasculature, lymphatic vessels, macrophages, and nerve cells-have remained unclear. This review synthesizes current knowledge of how the architecture of the testis unfolds and highlights the questions that remain to be explored, thus providing a roadmap for future studies that may help illuminate the causes of XY disorders of sex development, infertility, and testicular cancers. PMID- 24240235 TI - The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability. AB - Transcription is a major obstacle for replication fork (RF) progression and a cause of genome instability. Part of this instability is mediated by cotranscriptional R loops, which are believed to increase by suboptimal assembly of the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), the basic mRNP components, prevent R-loop stabilization. Here we show that yeast Npl3, the most abundant RNA-binding hnRNP, prevents R-loop-mediated genome instability. npl3Delta cells show transcription-dependent and R-loop-dependent hyperrecombination and genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells, and are reduced by RNase H1 overexpression. The resulting replication stress confers hypersensitivity to double-strand break-inducing agents. Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti cancer treatment. PMID- 24240236 TI - ATR-Chk1-APC/CCdh1-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress. AB - Cdc7 kinase regulates DNA replication. However, its role in DNA repair and recombination is poorly understood. Here we describe a pathway that stabilizes the human Cdc7-ASK (activator of S-phase kinase; also called Dbf4), its regulation, and its function in cellular responses to compromised DNA replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosome(Cdh1) (APC/C(Cdh1)) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C(Cdh1) through degradation of Cdh1 upon replication block, thereby stabilizing APC/C(Cdh1) substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4) with RAD18 disables foci formation by RAD18 and hinders chromatin loading of translesion DNA polymerase eta. These findings define a novel mechanism that orchestrates replication checkpoint signaling and ubiquitin proteasome machinery with the DNA damage bypass pathway to guard against replication collapse under conditions of replication stress. PMID- 24240237 TI - alpha-Catenin interacts with APC to regulate beta-catenin proteolysis and transcriptional repression of Wnt target genes. AB - Mutation of the adenomatous polyposis coli (APC) tumor suppressor stabilizes beta catenin and aberrantly reactivates Wnt/beta-catenin target genes in colon cancer. APC mutants in cancer frequently lack the conserved catenin inhibitory domain (CID), which is essential for beta-catenin proteolysis. Here we show that the APC CID interacts with alpha-catenin, a Hippo signaling regulator and heterodimeric partner of beta-catenin at cell:cell adherens junctions. Importantly, alpha catenin promotes beta-catenin ubiquitylation and proteolysis by stabilizing its association with APC and protecting the phosphodegron. Moreover, beta-catenin ubiquitylation requires binding to alpha-catenin. Multidimensional protein identification technology (MudPIT) proteomics of multiple Wnt regulatory complexes reveals that alpha-catenin binds with beta-catenin to LEF-1/TCF DNA binding proteins in Wnt3a signaling cells and recruits APC in a complex with the CtBP:CoREST:LSD1 histone H3K4 demethylase to regulate transcription and beta catenin occupancy at Wnt target genes. Interestingly, tyrosine phosphorylation of alpha-catenin at Y177 disrupts binding to APC but not beta-catenin and prevents repression of Wnt target genes in transformed cells. Chromatin immunoprecipitation studies further show that alpha-catenin and APC are recruited with beta-catenin to Wnt response elements in human embryonic stem cells (hESCs). Knockdown of alpha-catenin in hESCs prevents the switch-off of Wnt/beta-catenin transcription and promotes endodermal differentiation. Our findings indicate a role for alpha-catenin in the APC destruction complex and at Wnt target genes. PMID- 24240238 TI - Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly. AB - The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed to pericentric regions through RNAi-independent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation. PMID- 24240240 TI - Efficient charge generation by relaxed charge-transfer states at organic interfaces. AB - Interfaces between organic electron-donating (D) and electron-accepting (A) materials have the ability to generate charge carriers on illumination. Efficient organic solar cells require a high yield for this process, combined with a minimum of energy losses. Here, we investigate the role of the lowest energy emissive interfacial charge-transfer state (CT1) in the charge generation process. We measure the quantum yield and the electric field dependence of charge generation on excitation of the charge-transfer (CT) state manifold via weakly allowed, low-energy optical transitions. For a wide range of photovoltaic devices based on polymer:fullerene, small-molecule:C60 and polymer:polymer blends, our study reveals that the internal quantum efficiency (IQE) is essentially independent of whether or not D, A or CT states with an energy higher than that of CT1 are excited. The best materials systems show an IQE higher than 90% without the need for excess electronic or vibrational energy. PMID- 24240239 TI - Nucleotide-induced asymmetry within ATPase activator ring drives sigma54-RNAP interaction and ATP hydrolysis. AB - It is largely unknown how the typical homomeric ring geometry of ATPases associated with various cellular activities enables them to perform mechanical work. Small-angle solution X-ray scattering, crystallography, and electron microscopy (EM) reconstructions revealed that partial ATP occupancy caused the heptameric closed ring of the bacterial enhancer-binding protein (bEBP) NtrC1 to rearrange into a hexameric split ring of striking asymmetry. The highly conserved and functionally crucial GAFTGA loops responsible for interacting with sigma54 RNA polymerase formed a spiral staircase. We propose that splitting of the ensemble directs ATP hydrolysis within the oligomer, and the ring's asymmetry guides interaction between ATPase and the complex of sigma54 and promoter DNA. Similarity between the structure of the transcriptional activator NtrC1 and those of distantly related helicases Rho and E1 reveals a general mechanism in homomeric ATPases whereby complex allostery within the ring geometry forms asymmetric functional states that allow these biological motors to exert directional forces on their target macromolecules. PMID- 24240241 TI - Local electrostatic imaging of striped domain order in LaAlO3/SrTiO3. AB - The emerging field of complex oxide interfaces is generically built on one of the most celebrated substrates--strontium titanate (SrTiO3). This material hosts a range of phenomena, including ferroelasticity, incipient ferroelectricity, and most puzzlingly, contested giant piezoelectricity. Although these properties may markedly influence the oxide interfaces, especially on microscopic length scales, the lack of local probes capable of studying such buried systems has left their effects largely unexplored. Here we use a scanning charge detector--a nanotube single-electron transistor--to non-invasively image the electrostatic landscape and local mechanical response in the prototypical LaAlO3/SrTiO3 system with unprecedented sensitivity. Our measurements reveal that on microscopic scales SrTiO3 exhibits large anomalous piezoelectricity with curious spatial dependence. Through electrostatic imaging we unravel the microscopic origin for this extrinsic piezoelectricity, demonstrating its direct, quantitative connection to the motion of locally ordered tetragonal domains under applied gate voltage. These domains create striped potential modulations that can markedly influence the two-dimensional electron system at the conducting interface. Our results have broad implications to all complex oxide interfaces built on SrTiO3 and demonstrate the importance of microscopic structure to the physics of electrons at the LaAlO3/SrTiO3 interface. PMID- 24240242 TI - Enabling direct H2O2 production through rational electrocatalyst design. AB - Future generations require more efficient and localized processes for energy conversion and chemical synthesis. The continuous on-site production of hydrogen peroxide would provide an attractive alternative to the present state-of-the-art, which is based on the complex anthraquinone process. The electrochemical reduction of oxygen to hydrogen peroxide is a particularly promising means of achieving this aim. However, it would require active, selective and stable materials to catalyse the reaction. Although progress has been made in this respect, further improvements through the development of new electrocatalysts are needed. Using density functional theory calculations, we identify Pt-Hg as a promising candidate. Electrochemical measurements on Pt-Hg nanoparticles show more than an order of magnitude improvement in mass activity, that is, A g(-1) precious metal, for H2O2 production, over the best performing catalysts in the literature. PMID- 24240243 TI - A silicon carbide room-temperature single-photon source. AB - Over the past few years, single-photon generation has been realized in numerous systems: single molecules, quantum dots, diamond colour centres and others. The generation and detection of single photons play a central role in the experimental foundation of quantum mechanics and measurement theory. An efficient and high-quality single-photon source is needed to implement quantum key distribution, quantum repeaters and photonic quantum information processing. Here we report the identification and formation of ultrabright, room-temperature, photostable single-photon sources in a device-friendly material, silicon carbide (SiC). The source is composed of an intrinsic defect, known as the carbon antisite-vacancy pair, created by carefully optimized electron irradiation and annealing of ultrapure SiC. An extreme brightness (2*10(6) counts s(-1)) resulting from polarization rules and a high quantum efficiency is obtained in the bulk without resorting to the use of a cavity or plasmonic structure. This may benefit future integrated quantum photonic devices. PMID- 24240244 TI - Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy and safety of two low-dose levonorgestrel intrauterine contraceptive systems. METHODS: Nulliparous and parous women aged 18 35 years with regular menstrual cycles (21-35 days) requesting contraception were randomized to 3 years of treatment with one of two levonorgestrel intrauterine contraceptive systems: 13.5 mg total content or 19.5 mg total content. The primary outcome was the pregnancy rate, calculated as the Pearl Index. RESULTS: Overall, 1,432 and 1,452 women in the 13.5 mg intrauterine contraceptive system and 19.5 mg intrauterine contraceptive system groups, respectively, had a placement attempted and were included in the full analysis set to evaluate efficacy and safety. Mean (standard deviation) age was 27.1 (4.8) years; 39.2% were nulliparous. Over the 3-year study period, 0.33 pregnancies per 100 women years (95% confidence interval [CI] 0.16-0.60) were observed with the 13.5 mg intrauterine contraceptive system compared with 0.31 per 100 women-years (95% CI 0.15-0.57) with the 19.5 mg intrauterine contraceptive system. Kaplan-Meier estimates for that period were 0.009 and 0.010, respectively. At least partial expulsions occurred in 4.56% and 3.58% and discontinuation rates resulting from a reported adverse event occurred in 21.9% and 19.1%, respectively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic inflammatory disease and one partial uterine perforation. CONCLUSIONS: Both lower dose levonorgestrel intrauterine contraceptive systems were highly effective for 3 years of use and generally well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00528112. LEVEL OF EVIDENCE: : I. PMID- 24240245 TI - Full data consistency conditions for cone-beam projections with sources on a plane. AB - Cone-beam consistency conditions (also known as range conditions) are mathematical relationships between different cone-beam projections, and they therefore describe the redundancy or overlap of information between projections. These redundancies have often been exploited for applications in image reconstruction. In this work we describe new consistency conditions for cone-beam projections whose source positions lie on a plane. A further restriction is that the target object must not intersect this plane. The conditions require that moments of the cone-beam projections be polynomial functions of the source positions, with some additional constraints on the coefficients of the polynomials. A precise description of the consistency conditions is that the four parameters of the cone-beam projections (two for the detector, two for the source position) can be expressed with just three variables, using a certain formulation involving homogeneous polynomials. The main contribution of this work is our demonstration that these conditions are not only necessary, but also sufficient. Thus the consistency conditions completely characterize all redundancies, so no other independent conditions are possible and in this sense the conditions are full. The idea of the proof is to use the known consistency conditions for 3D parallel projections, and to then apply a 1996 theorem of Edholm and Danielsson that links parallel to cone-beam projections. The consistency conditions are illustrated with a simulation example. PMID- 24240246 TI - Gene transfer by electroporation in betulaceae protoplasts: Alnus incana. AB - The Escherichia coli beta-glucuronidase gene (GUS) was introduced into Alnus incana (L.) Moench protoplasts by electroporation. Level of GUS transient gene expression was increased by increasing DNA concentrations of pBI 221 plasmid and was affected by the amplitude and duration of the applied electric pulse as well as by the presence of polyethylene glycol (PEG) in the electroporation medium. An optimal level of GUS activity was obtained after electroporation with a capacitive discharge of 500 V/cm and 71 ms-duration. This transformation procedure is simple and efficient. These results motivated us to investigate this method as a possible way of achieving the stable transformation of actinorhizal alder. PMID- 24240247 TI - Plant regeneration from protoplasts of embryogenic suspension cultures of orchardgrass (Dactylis glomerata L.). AB - An embryogenic suspension culture of orchardgrass (Dactylis glomerata L.) consisting of small, embryogenic cell clusters was obtained from callus formed on basal sections of young leaves through a process of selective enrichment. These suspensions were used as a source of protoplasts. The isolated protoplasts divided at a frequency of 0.5-10% when plated in an agarose solidified culture medium. Conditioned medium, in which embryogenic Dactylis suspension cultures had been grown, was found to increase the rate of cell colony formation. Protoplast derived colonies grew rapidly in a bead-type culture system of floating agarose slabs in liquid medium. New suspension cultures formed as the colonies grew out of the agarose. These cultures were embryogenic and formed green plantlets when plated on a solid medium lacking auxin. The plantlets were established in soil and grown to mature plants. PMID- 24240248 TI - Induction of heavy-metal binding phytochelatins by inoculation of cell cultures in standard media. AB - A large increase in phytochelatin (PC) synthesis occurred when cell cultures of different plant species were transferred from spent medium to fresh standard media. Phytochelatin accumulation correlated with the initial concentration of zinc ions in the nutrient solution. After reaching stationary growth phase, phytochelatins had almost disappeared from the cells which indicates a high turnover of these molecules under normal conditions. No significant formation of the heavy-metal complexing phytochelatins was observed if the microelement ions zinc and copper were omitted from the nutrient solutions for plant cell cultures. Both the induction and degradation phenomena of these peptides indicate that phytochelatins are involved in metal ion homeostasis in plants. PMID- 24240249 TI - Transgenic rice plants produced by electroporation-mediated plasmid uptake into protoplasts. AB - Transgenic rice plants have been regenerated by somatic embryogenesis from cell suspension derived protoplasts electroporated with plasmid carrying the NPTII gene under the control of the 35S promoter from cauliflower mosaic virus. Heat shock of protoplasts prior to electroporation maximised the throughput of kanamycin resistant colonies. Omission of kanamycin from the medium for plant regeneration was essential for the recovery of transgenic rice plants carrying the NPTII gene. This report of the production of kanamycin resistant transgenic rice plants establishes the use of protoplasts for rice genetic engineering. PMID- 24240250 TI - In vitro plant regeneration of leguminous trees (Albizia spp). AB - Hypocotyl explants of three leguminous forest tree species, Albizia amara, A. lucida and A. richardiana, have differentiated shoot buds on B5 basal medium. Maximum number of shoots per explant developed on basal medium augmented with 2,4 D (0.1 MUM) in A. amara (2) and BA (10 MUM) for both A. lucida (2) and A. richardiana (1.6). Higher concentrations of auxins in the medium, in general, enhanced rooting and callusing but cytokinins promoted the growth of green calli. BA enchanced the differentiation of shoots in the three species. The in vitro grown shoots of A. amara and A. richardiana, after subculturing on B5+1 MUM IAA developed roots (up to 30-40%). These plants have been successfully transferred to the field. PMID- 24240251 TI - An investigation of the intracellular site of anthocyanoplasts using isolated protoplasts and vacuoles. AB - Microscopic observations made during preparation of protoplasts and vacuoles from red radish seedling hypocotyl (Raphanus sativus L.) show that anthocyanoplasts, the strongly pigmented bodies present in the pigmented cells of the hypodermis, begin as apparently membranous vesicles in the cytoplasm made visible by the deposition and accumulation of anthocyanins, but only rarely appear in the isolated vacuole. Isolation of protoplasts and vacuoles was also achieved from mung bean seedling hypocotyl (Vigna radiata L Wilczek), red cabbage leaf (Brassica oleracea L.) and Prunus x yedoensis Matsum callus. Anthocyanoplasts were usually in the vacuole, although sometimes in the cytoplasm, of the mung bean and cabbage, but were never seen in vacuoles of Prunus callus. PMID- 24240252 TI - Long-term effect of electroporation on enhancement of growth and plant regeneration of colt cherry (Prunus avium * pseudocerasus) protoplasts. AB - Electric pulses applied to Colt cherry protoplasts enhanced the long-term growth and plant regeneration of protoplast-derived tissues. Protoplasts isolated from long-term cultured tissues derived from electroporated protoplasts retained the ability to enter division in culture earlier and with a higher frequency of plant regeneration than untreated cell suspension protoplasts. PMID- 24240253 TI - Selection of Brassica napus L. embryogenic microspores by flow sorting. AB - Flow cytometry can be used to select and sort microspore subpopulations of Brassica napus cv. Topas. Data obtained from embryogenic microspore populations were used to identify potentially embryogenic microspores from developmentally heterogeneous microspore populations based on differences in forward light scatter and green autofluorescence. Culture enrichment for embryogenic microspores is possible. Frequencies of 8 and 14% microspore embryogenesis were obtained when selected 16 h and 72 h after culture initiation. This represents 5- and 13-fold increase in microspore embryogenesis compared to non-sorted controls. PMID- 24240254 TI - Plant regeneration from somatic embryogenic suspension cultures of cotton (Gossypium hirsutum L.). AB - Maintainable, highly embryogenic suspension cultures of cotton (Gossypium hirsutum L. cv. 'Coker 310') have been obtained. Callus cultures were initiated from cotyledonary tissues from aseptically-germinated seedlings. To establish the suspension cultures, callus tissue was placed in a liquid medium containing either 0.5 mg/l picloram or 0.1 mg/l 2,4-dichlorophenoxyacetic acid. For proliferation of the embryogenic suspension, 5 mg/l of 2,4-dichlorophenoxyacetic acid was used. Embryo development took place when the embryogenic tissue was transferred to an auxin-free liquid medium containing 15 mM glutamine. Early embryo development was fairly synchronous and large numbers of somatic embryos were produced. Regenerated plants were fertile and smaller than seed-derived plants. PMID- 24240255 TI - Ethylene and in vitro culture of potato: suppression of ethylene generation vastly improves protoplast yield, plating efficiency and transient expression of an alien gene. AB - Ethylene release by potato shoots cultured in closed boxes was suppressed by the addition of silver thiosulfate to the culture medium. Shoots cultured in the presence of silver thiosulfate produced appreciably more tissue and the yield of protoplasts per unit tissue mass was vastly increased, resulting in an 8 fold increase of protoplast yield per shoot. Exposure of pricked leaves to macerating enzymes facilitated ethylene generation. Leaves of shoots which were previously cultured in silver thiosulfate containing medium generated much less ethylene than leaves from control shoots and this generation could be further reduced by the addition of acetylsalicylic acid during maceration. The capability of polyethylene glycol treated potato protoplasts to produce microcalli was vastly increased by the addition of silver thiosulfate during exposure of protoplasts to Ca(NO3)2 following the polyethylene glycol treatment. Similarly, when a plasmid (pCAP212) containing an expressible gene for chloramphenicol acetyltransferase was introduced into potato protoplasts through a polyethylene glycol treatment, the transient expression of acetyltransferase was very much increased by the addition of a short incubation of the protoplasts with silver thiosulfate. PMID- 24240256 TI - Embryogenesis following cryopreservation in isolated microspores of rapeseed (Brassica napus L.). AB - A simple procedure is described for cryopreservation of isolated microspores of rapeseed in liquid nitrogen without loss of embryogenic capacity (i.e. embryogenes is can still be induced following freezing). Microspores frozen in Lichter's (1982) medium with 13% sucrose produced ca. 10% of the embryos yielded by an unfrozen control. Microspores frozen in Lichter's medium with 13% sucrose, and supplemented with 0.5 M glycerol and 0.5 M DMSO produced no embryos. Regeneration of embryos obtained from frozen microspores yielded 88% diploid and 12% haploid plants, while embryos from unfrozen controls produced 7% diploids and 93% haploids. The potential to increase the efficiency of the rapeseed haploidy system using cryopreservation is discussed in light of these results. PMID- 24240257 TI - Semi-continuous production of sanguinarine and dihydrosanguinarine by Papaver somniferum L. cell suspension cultures treated with fungal homogenate. AB - Papaver somniferum L. (opium poppy) cells were elicited with a Botrytis sp. homogenate and cultured by a semi-continuous process. Elicitation induced synthesis of sanguinarine and dihydrosanguinarine. Significant release of both alkaloids into the culture medium occurred. Medium exchange at 2-day intervals enabled product recovery from spent medium and maintained culture viability. Culture growth was not inhibited by elicitor treatment necessitating sub-culture prior to re-elicitation. Re-elicited cultures displayed an increasing sensitivity (reduced growth rate, higher alkaloid yield) to the elicitor with each successive treatment and did not survive a fourth elicitation. PMID- 24240258 TI - Wheat protoplast culture: embryogenic colony formation from protoplasts. AB - Wheat (Triticum aestivum L. cv Chinese Spring) protoplasts were isolated from immature embryos or embryogenic calli (3-4 weeks of culture on MS medium with 32 mg/1 dicamba) and cultured in R2 medium containing 2 mg/1 2,4-D by the nurse culture methods originally developed for rice protoplasts (Kyozuka et al. 1987). Protoplasts isolated from embryogenic calli started to divide within 3-5 days and formed colonies at frequencies up to 2% after 3-4 weeks of culture, while protoplasts isolated from immature embryos formed colonies at much lower frequency (less than 0.1%). Some of these colonies were "embryogenic", and they appeared at a frequency of approximately 0.5% of colonies formed when callus derived protoplasts were used. From two of those "embryogenic" colonies, calli were regenerated and albino shoots and roots were obtained. PMID- 24240259 TI - Direct somatic embryogenesis from protoplasts of Citrus mitis Blanco. AB - Protoplasts isolated from embryogenic suspension cultures of Citrus mitis were cultured in a medium without any plant growth substances. Somatic embryos developed directly from protoplasts without an obvious intervening callus phase. As many as 1,800 somatic embryos developed from 4 ml of protoplast suspension (density 2*10(6)/ml) cultured for 35 days. Upon transferring the embryoids to medium with 1 mgl(-1) GA3, they developed into plant-lets. Rooted plantlets were obtained in 3 months after protoplast isolation. PMID- 24240261 TI - In vitro regeneration in Allium species. AB - An attempt to induce shoot regeneration from leaf disc explants from Allium sativum L., A. porrum L., and A. schoenoprasum L. and the induction of shoot regeneration from single flower-bud receptacles in A. porrum is presented. While the regeneration rate from leaf disc explants was low, an efficient method for propagating A. porrum in vitro was obtained by cultivating single flower-bud receptacles. The shoot regeneration ability was strongly controlled by the genotype. Up to 294 shoots per leek plant could be harvested. Simultaneously the same plant could be used for seed production and bulbil formation in vivo. The efficiency of the in vitro multiplication method described allows the integration of this procedure into breeding programmes of A. porrum. PMID- 24240260 TI - Production of kanamycin resistant rice tissues following DNA uptake into protoplasts. AB - Rice protoplasts (Oryza sativa L. v Taipei 309) have been transformed to kanamycin resistance following uptake of pCaMVNEO induced by electroporation, PEG and PEG combined with electroporation. Protoplast-derived colonies selected on medium containing 100 MUg/ml of kanamycin expressed NPTII activity, and contained DNA that hybridised to a 1.0 Kb BamHI fragment of pCaMVNEO carrying the NPTII gene. Expression of the transformation frequency in relative terms (number of kanamycin resistant colonies compared to the number of colonies on kanamycin free medium) gave frequencies of 26.1%, 8.5% and 2.9% following electroporation, PEG and PEG with electroporation respectively. In absolute terms (number of kanamycin resistant colonies compared to the number of protoplasts plated) these represent frequencies of 19.9*10(-5), 9.0*10(-5) and 2.7*10(-5) for the three procedures. PMID- 24240262 TI - A novel method to produce Anabaena-free Azolla by in vitro fertilization of micromanipulated megasporocarps. AB - In the Azolla-Anabaena azollae symbiotic system, Anabaena akinetes get entrapped between the indusium and the apical cap of the megaspore apparatus during megasporocarp development, thus maintaining the continuity of the cyanobacterial association throughout the life cycle of the fern. The entrapped akinetes serve as the source of inoculum for infecting the new sporophyte when it is emerging from the megaspore apparatus. A procedure to generate Anabaena-free Azolla was developed by fertilizing the germinating megasporocarps in which the indusium along with the akinetes were removed by micromanipulation. This method has the advantage of not requiring drastic treatments of Azolla with antibiotics to eliminate the endosymbiotic cyanobacterial cells. Details of this new method and its usefulness in studies aimed at recombination of Azolla with Anabaena azollae are discussed. PMID- 24240263 TI - Sandalwood plantlets from 'Synthetic seeds'. AB - Somatic embryos of sandalwood (Santalum album) were encapsulated in an alginate matrix to prepare 'Synthetic seeds'. Encapsulated single embryos germinated to form plants with roots and shoots. Embryogenic cell suspensions encapsulated and stored at 4 degrees C for 45 days produced embryos when recultured as suspensions. PMID- 24240264 TI - Callus and embryoid formation from protoplasts of Helianthus annuus. AB - Sunflower hypocotyl protoplasts have been isolated and cultured. Optimum plating density for cell division and colony formation was in the range of 5 to 7*10(4) cells/mi in an agarose medium supplemented with BAP (1 mg/l) and NAA (1 mg/l). Plating efficiency was 60% after 21 days of culture. In the resultant culture a mixed population of calli and embryoids was observed. Thirty seven percent of the cell clusters exhibited a developmental pattern similar to an embryoid. Many stages of embryogenesis were observed in the same cultures. PMID- 24240265 TI - Microspore development in cultured maize anthers. AB - The present study follows in vivo and in vitro microspore development utilizing an anther culture-responsive maize genotype (Pa91*FR16) and a DNA-specific fluorescent dye (mithramycin). Cultured anthers were sampled at various times and scored for abnormal microspore divisions, multicellular masses, and embryo-like structures. The frequency of abnormal microspore divisions reached a peak during the first 7 days in culture and then declined. The vegetative nucleus was mitotically active in culture with over 50% of the induced microspores exhibiting this type of division. Multicellular masses and embryo-like structures first appeared in the 14 and 25 day samples, respectively. Most of the microspores did not reach the multicellular stage and an even greater mortality occurred during the formation of embryo-like structures. PMID- 24240266 TI - Somatic embryos from callus of Sequoia sempervirens. AB - Compact calli with a potential for somatic embryogenesis were obtained from complete or split mature zygotic embryos or from cotyledons and hypocotyls of in vitro grown seedlings of Sequoia sempervirens. Somatic embryos which showed a typical bipolar structure, were formed together with adventitious buds. When placed on filter paper supports they developed into complete plantlets. Of the various combinations tested, culture medium adapted from Murashige and Skoog mineral solution complemented with 6-benzylaminopurine (2 MUM), kinetin (2 MUM) and 2,4-dichlorophenoxyacetic acid (2.5 MUM) was established as the optimal for somatic embryo production. PMID- 24240267 TI - Regeneration of plants from leaf explants of Cucumis melo cv. Pusa Sharbati. AB - Leaves of three different sizes excised from 14, 21, 28 and 35-day-old seedlings of Cucumis melo were cultured on a MS medium supplemented with a range and combination of growth regulators. Maximum shoot differentiation from the leaf explants occurred in the combined presence of BAP and 2iP at equimolar concentration of 1 MUM. Regeneration potential of leaves declined with increasing size of the leaves and the age of the donor seedlings. For elongation the shoots were transferred to MS+BAP [1 MUM]. Such shoots were rooted with 75% frequency on MS+IAA [0.5 MUM]. The plants have been established in pots. PMID- 24240268 TI - Improved plant regeneration from maize callus cultures using 6-benzylaminopurine. AB - A new protocol for regenerating plants from cultured type I callus of the maize (Zea mays L.) inbred Pa91 includes growing the callus on medium containing 3.5 mg/l (15.5 MUM) of the cytokinin 6-benzylaminopurine (6BA) for 3 to 6 d and then moving the callus to medium containing no growth regulators (H medium) for an additional 15 to 21 d, where the plants actually develop. The number of plants regenerated from the 6BA treated callus was 113% to 148% greater than the number of plants produced from callus placed directly on H medium. This increased plant regeneration induced by 6BA seemed to maximize the number of plants regenerated from a gram of callus and was slightly affected by callus age or prior treatment of callus with AgNO3. Exposure to 6BA for 9 d greatly reduced shoot and root development, and longer exposures totally prevented root formation. This inhibition of root formation could be reversed only slightly by naphthaleneacetic acid. The data indicate that high concentrations of 6BA are effective for increasing plant regeneration from maize callus cultures when short exposure times are used. This procedure has also been effective for regenerating many plants from the inbreds H99 and Mo17. PMID- 24240269 TI - Variability in tissue cultures of Choisya ternata. III comparing alkaloid production in cell lines obtained by various strategies. AB - Callus cultures of Choisya ternata have been prepared by different strategies: aggregate clones, subclones and protoclones obtained from well-established strains; protoclones obtained from mesophyll tissue; cultures transformed by Agrobacterium tumefaciens. All of them show high variability in their dihydrofuroquinoline alkaloid production. As compared to the alkaloid content of the whole plant, one alkaloid (platydesminium) could be obtained in higher amounts in some lines, but it was impossible to get high-balfourodinium accumulating lines. Moreover balfourodinium-producing capacities were lower in transformed cells as compared to those of normal cell lines. PMID- 24240270 TI - A method for the rapid production of fine plant cell suspension cultures. AB - A method has been devised which allows the rapid production of fine suspension cultures of small aggregate size from suspension cultures of large average aggregate size, such as those of Capsicum frutescens. The method, which uses a Waring blender for aseptic homogenisation of cultures, has also been shown to be effective in rapidly producing suspension cultures from callus cultures. The suspension cultures so produced are particularly useful for immobilisation, such as in porous polyurethane foam matrices. PMID- 24240271 TI - In vitro selection for salt tolerant lines in Lycopersicon peruvianum. AB - A salt-tolerant callus line of Lycopersicon peruvianum has been obtained by exposing the cells, in suspension cultures and then in callus, to increasing concentrations of NaCl (50-350mM). This selected line grew better than the nonselected line at all levels of NaCl. Moreover, this selected line grew better in media containing salt than in those without it. It retained its tolerance after subculture for 3 passages (3 months) on salt-free medium. The growth of the selected line in mannitol was similar to that of the nonselected line, which suggested that the superiority of the selected line under salt stress was not due to osmotic stress tolerance. The ions SO 4 (--) and K(+) were highly toxic to L. peruvianum root callus, while Na(+), Mg(++) and Cl(-) were less toxic. PMID- 24240272 TI - Clonal propagation of Cephaelis ipecacuanha. PMID- 24240274 TI - Tailoring photocatalytic nanostructures for sustainable hydrogen production. AB - Photocatalysis is an important component for achieving sustainability in chemical transformations. It requires light absorption by a semiconductor and efficient extraction of the photogenerated electron-hole pairs to chemically active sites. One of the main problems in photocatalytic materials is to avoid electron-hole recombination following excitation. Tailored nanostructures offer a new way for achieving this goal by facilitating electron-hole separation. Nanoscaling of materials offers additional opportunities to generate unique photocatalysts that demonstrated novel light absorption, thermodynamic and kinetic properties. In this feature article we highlight some recent approaches towards the preparation of materials and nanostructures that showed improved activity for the sustainable production of hydrogen. This reaction has received much attention for the supply of future demand both for chemical industry and energy-related applications. PMID- 24240273 TI - Cell cycle delay in murine pre-osteoblasts is more pronounced after exposure to high-LET compared to low-LET radiation. AB - Space radiation contains a complex mixture of particles comprised primarily of protons and high-energy heavy ions. Radiation risk is considered one of the major health risks for astronauts who embark on both orbital and interplanetary space missions. Ionizing radiation dose-dependently kills cells, damages genetic material, and disturbs cell differentiation and function. The immediate response to ionizing radiation-induced DNA damage is stimulation of DNA repair machinery and activation of cell cycle regulatory checkpoints. To date, little is known about cell cycle regulation after exposure to space-relevant radiation, especially regarding bone-forming osteoblasts. Here, we assessed cell cycle regulation in the osteoblastic cell line OCT-1 after exposure to various types of space-relevant radiation. The relative biological effectiveness (RBE) of ionizing radiation was investigated regarding the biological endpoint of cellular survival ability. Cell cycle progression was examined following radiation exposure resulting in different RBE values calculated for a cellular survival level of 1 %. Our findings indicate that radiation with a linear energy transfer (LET) of 150 keV/MUm was most effective in inducing reproductive cell killing by causing cell cycle arrest. Expression analyses indicated that cells exposed to ionizing radiation exhibited significantly up-regulated p21(CDKN1A) gene expression. In conclusion, our findings suggest that cell cycle regulation is more sensitive to high-LET radiation than cell survival, which is not solely regulated through elevated CDKN1A expression. PMID- 24240275 TI - Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation. AB - BACKGROUND: Exposure to particulate matter<=2.5 MUm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown. OBJECTIVES: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation. METHODS: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system. RESULTS: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting alpha2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure-induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor-kappaB (NF kappaB) pathway activation. CONCLUSION: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation. PMID- 24240277 TI - An exactly solvable model for quantum communications. AB - Information theory establishes the ultimate limits on performance for noisy communication systems. Accurate models of physical communication devices must include quantum effects, but these typically make the theory intractable. As a result, communication capacities--the maximum possible rates of data transmission -are not known, even for transmission between two users connected by an electromagnetic waveguide with Gaussian noise. Here we present an exactly solvable model of communication with a fully quantum electromagnetic field. This gives explicit expressions for all point-to-point capacities of noisy quantum channels, with implications for quantum key distribution and fibre-optic communications. We also develop a theory of quantum communication networks by solving some rudimentary models including broadcast and multiple-access channels. We compare the predictions of our model with the orthodox Gaussian model and in all cases find agreement to within a few bits. At high signal-to-noise ratios, our simple model captures the relevant physics while remaining amenable to exact solution. PMID- 24240276 TI - Crystal structures of the Lsm complex bound to the 3' end sequence of U6 small nuclear RNA. AB - Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes. Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3' end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3' fragment of U6 snRNA, at 2.8 A resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3-2-8-4-7-5-6. The four uridine nucleotides at the 3' end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3' end is sandwiched by His 36 and Arg 69 from Lsm3, through pi-pi and cation-pi interactions, respectively. The distinctive end recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing. PMID- 24240278 TI - Low investment in sexual reproduction threatens plants adapted to phosphorus limitation. AB - Plant species diversity in Eurasian wetlands and grasslands depends not only on productivity but also on the relative availability of nutrients, particularly of nitrogen and phosphorus. Here we show that the impacts of nitrogen:phosphorus stoichiometry on plant species richness can be explained by selected plant life history traits, notably by plant investments in growth versus reproduction. In 599 Eurasian sites with herbaceous vegetation we examined the relationship between the local nutrient conditions and community-mean life-history traits. We found that compared with plants in nitrogen-limited communities, plants in phosphorus-limited communities invest little in sexual reproduction (for example, less investment in seed, shorter flowering period, longer lifespan) and have conservative leaf economy traits (that is, a low specific leaf area and a high leaf dry-matter content). Endangered species were more frequent in phosphorus limited ecosystems and they too invested little in sexual reproduction. The results provide new insight into how plant adaptations to nutrient conditions can drive the distribution of plant species in natural ecosystems and can account for the vulnerability of endangered species. PMID- 24240279 TI - Late-twentieth-century emergence of the El Nino propagation asymmetry and future projections. AB - The El Nino/Southern Oscillation (ENSO) is the Earth's most prominent source of interannual climate variability, exerting profound worldwide effects. Despite decades of research, its behaviour continues to challenge scientists. In the eastern equatorial Pacific Ocean, the anomalously cool sea surface temperatures (SSTs) found during La Nina events and the warm waters of modest El Nino events both propagate westwards, as in the seasonal cycle. In contrast, SST anomalies propagate eastwards during extreme El Nino events, prominently in the post-1976 period, spurring unusual weather events worldwide with costly consequences. The cause of this propagation asymmetry is currently unknown. Here we trace the cause of the asymmetry to the variations in upper ocean currents in the equatorial Pacific, whereby the westward-flowing currents are enhanced during La Nina events but reversed during extreme El Nino events. Our results highlight that propagation asymmetry is favoured when the westward mean equatorial currents weaken, as is projected to be the case under global warming. By analysing past and future climate simulations of an ensemble of models with more realistic propagation, we find a doubling in the occurrences of El Nino events that feature prominent eastward propagation characteristics in a warmer world. Our analysis thus suggests that more frequent emergence of propagation asymmetry will be an indication of the Earth's warming climate. PMID- 24240282 TI - We need to know our limitations: genetic testing for complex traits. PMID- 24240280 TI - Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A. AB - Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders. BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport). BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals. Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other: gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor binding domain of the toxin. Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor. In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain, but the molecular details of the interaction between BoNT/A and SV2 are unknown. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). SV2C-LD consists of a right-handed, quadrilateral beta-helix that associates with BoNT/A RBD mainly through backbone-to-backbone interactions at open beta-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Competition experiments identified a peptide that inhibits the formation of the complex. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties. PMID- 24240281 TI - Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export. AB - Eukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes. Nuclear export is a key, irreversible step in pre-ribosome maturation, but mechanisms underlying the timely acquisition of export competence remain poorly understood. Here we show that a conserved Saccharomyces cerevisiae GTPase Nug2 (also known as Nog2, and as NGP-1, GNL2 or nucleostemin 2 in human) has a key role in the timing of export competence. Nug2 binds the inter-subunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3, a key pre-60S export adaptor. Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G-domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodelling factors, the Rea1 ATPase and its co-substrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with nug2 mutants. Release of Nug2 from pre-60S particles requires both its K(+) dependent GTPase activity and the remodelling ATPase activity of Rea1. We conclude that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery. PMID- 24240283 TI - Genetic influence on athletic performance. AB - PURPOSE OF REVIEW: To summarize the existing literature on the genetics of athletic performance, with particular consideration for the relevance to young athletes. RECENT FINDINGS: Two gene variants, ACE I/D and ACTN3 R577X, have been consistently associated with endurance (ACE I/I) and power-related (ACTN3 R/R) performance, though neither can be considered predictive. The role of genetic variation in injury risk and outcomes is more sparsely studied, but genetic testing for injury susceptibility could be beneficial in protecting young athletes from serious injury. Little information on the association of genetic variation with athletic performance in young athletes is available; however, genetic testing is becoming more popular as a means of talent identification. Despite this increase in the use of such testing, evidence is lacking for the usefulness of genetic testing over traditional talent selection techniques in predicting athletic ability, and careful consideration should be given to the ethical issues surrounding such testing in children. SUMMARY: A favorable genetic profile, when combined with an optimal training environment, is important for elite athletic performance; however, few genes are consistently associated with elite athletic performance, and none are linked strongly enough to warrant their use in predicting athletic success. PMID- 24240284 TI - The genetic autopsy. AB - PURPOSE OF REVIEW: To assess the relevance of perinatal and pediatric autopsies in genetic and metabolic diseases. RECENT FINDINGS: Genetic investigations are an important component of fetal autopsies. Despite the advances in imaging diagnosis, the autopsy can identify abnormalities not seen on ultrasound or MRI, as confirmed in recent comparative studies. This is crucial in the diagnosis of syndromic conditions in which the information may be essential to determine the syndrome. Genetic tests may also have a role in the investigation of intrauterine growth restriction and unexplained stillbirth. New techniques have increased the diagnostic yield, even in cases of macerated fetuses.The genetic autopsy is not limited to fetal loss. Genetic abnormalities underlie many cases presenting as sudden unexpected death in infancy, childhood and adolescence, and the need to obtain appropriate samples for genetic analysis applies not only to fetal autopsies. SUMMARY: Fetal autopsies are still the gold standard in diagnosis of fetal abnormalities. Genetic studies are an important component, not only in cases of congenital malformations, but also in unexplained intrauterine death and sudden unexpected death in infancy, as well as in children and adults. PMID- 24240285 TI - Genetics of nonsyndromic obesity. AB - PURPOSE OF REVIEW: Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and genetic susceptibility contributed by common and rare genetic variants. This review describes the recent advances in understanding the role of genetics in obesity. RECENT FINDINGS: New susceptibility loci and genetic variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from early life experiences. Genetic prediction scores derived from selected genetic variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. Genetic variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently. SUMMARY: We can expect discovery of more rare genetic variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences genetic expression and which mediate the gene-environment interaction. PMID- 24240286 TI - Neuromuscular disorders: from diagnosis to translational research, drug development and clinical trials. PMID- 24240287 TI - Current advances in drug development in spinal muscular atrophy. AB - PURPOSE OF REVIEW: Spinal muscular atrophy (SMA) is a pediatric neuromuscular condition characterized by progressive proximal muscle weakness. It is one of the most common genetic causes of infant mortality across different races and is caused by mutation of the survival of motor neuron 1 (SMN1) gene on chromosome 5q13. RECENT FINDINGS: To date, there have been many therapeutics developments for SMA targeting various potential pathways such as increasing SMN gene expression, enhancing SMN2 exon 7 inclusion, neuroprotection, cell replacement, and gene therapy. SUMMARY: Although SMA remains an incurable disease to date, recent advances in the field of basic and translational research have enhanced our understanding of the pathogenesis of the disease and opened new possibilities for therapeutic intervention. This article reviews and highlights past and current translational research on SMA therapeutics. PMID- 24240288 TI - Pediatric Guillain-Barre syndrome. AB - PURPOSE OF REVIEW: Guillain-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis in children. This review discusses the heterogeneous presentations of this disorder, the frequency of disease-related complications and the importance of assiduous clinical care in pediatric GBS. RECENT FINDINGS: Recent reports have highlighted the variable clinical and neurophysiologic subtypes of pediatric GBS, and emphasized the value of imaging in diagnosis of this disorder. SUMMARY: Diagnosis of pediatric GBS is often delayed because of its variable presentation. Early recognition and treatment decrease long-term morbidity and mortality. Recent research has cast light on the variable presentations and pathogenesis of the numerous subtypes of this condition, and is now focusing upon a better understanding of the natural history of GBS. PMID- 24240289 TI - Muscular dystrophy: new challenges and review of the current clinical trials. AB - PURPOSE OF REVIEW: We provide a review of recent standards of care and therapeutic development in different forms of muscular dystrophies. This topic is relevant as the improved understanding of these disorders has not only led to a better definition of clinical course and to the development of standards of care for individual types of muscular dystrophies, but also culminated in different therapeutic approaches. RECENT FINDINGS: Recent natural history studies have demonstrated the impact of new standards of care in different forms of muscular dystrophies, and identified areas of clinical management in which further developments are needed. The majority of the experimental studies are focused on Duchenne muscular dystrophy. Some of them target patients with specific mutations, such as antisense oligonucleotides, to induce exon skipping of specific mutations or drugs developed to allow read-through of nonsense mutations, whereas other therapies deal with secondary aspects of muscle degeneration, aiming, for example, at reducing inflammation or apoptosis, and may also be suitable for other forms of muscular dystrophies. SUMMARY: The advances in the field of muscular dystrophy have resulted in improved clinical course and survival. The encouraging results of early experimental studies could further improve these outcomes in the future. PMID- 24240291 TI - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy and other primary immunodeficiency diseases help to resolve the nature of protective immunity against chronic mucocutaneous candidiasis. AB - PURPOSE OF REVIEW: This review summarizes and discusses the most recent and important publications describing Mendelian diseases associated with susceptibility to chronic mucocutaneous candidiasis (CMC) as a means of gaining insight into the pathogenesis of this immunodeficiency. RECENT FINDINGS: Impairment to T helper 17 (Th17) cell-associated signalling pathways are common in immunodeficiency syndromes associated with CMC infections. Mutations in CARD9, STAT3, IL17RA, IL17F, STAT1, and IL12RB and polymorphisms in Dectin 1 and interleukin-22 (IL-22) encoding genes have been shown to impair the development or function of Th17 cells and are associated with susceptibility to candidiasis. Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy have revealed autoimmunity to Th17 cytokines and cells as the basis for CMC. IL-17A, IL-17F, and IL-22 induce production of antimicrobial peptides and chemoattractants that recruit neutrophils in response to invading fungi. Th17 cell-associated cytokines may play a role in shaping the host's microbiome (that competes with C. albicans) preventing overgrowth of this pathogen. Recent evidence also suggests that IL-22 together with IL-17F might be the most important Th17 cytokine in protection against Candida. SUMMARY: Dissection of critical molecular and immunological mechanisms will allow the development of new treatments for primary and secondary immunodeficiency disorders resulting in chronic Candida infections. PMID- 24240290 TI - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX related disorders: an evolving web of heritable autoimmune diseases. AB - PURPOSE OF REVIEW: To summarize recent progress in our understanding of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders. RECENT FINDINGS: A number of Mendelian disorders of immune dysregulation and autoimmunity have been noted to result from defects in T regulatory cell, development and function. The best characterized of these is IPEX, resulting from mutations affecting FOXP3. A number of other gene defects that affect T regulatory cell function also give rise to IPEX-related phenotypes, including loss-of-function mutations in CD25, STAT5b and ITCH. Recent progress includes the identification of gain-of-function mutations in STAT1 as a cause of an IPEX-like disease, emerging FOXP3 genotype/phenotype relationships in IPEX, and the elucidation of a role for the microbiota in the immune dysregulation associated with regulatory T cell deficiency. SUMMARY: An expanding spectrum of genetic defects that compromise T regulatory cell function underlies human disorders of immune dysregulation and autoimmunity. Collectively, these disorders offer novel insights into pathways of peripheral tolerance and their disruption in autoimmunity. PMID- 24240292 TI - The expanding spectrum of the autoimmune lymphoproliferative syndromes. AB - PURPOSE OF REVIEW: Several autoimmune lymphoproliferative syndromes have been described lately. We review here the main clinical and laboratory findings of these new disorders. RECENT FINDINGS: The prototypical autoimmune lymphoproliferative syndrome (ALPS) has had its diagnostic criteria modified, somatic mutations in RAS genes were found to cause an ALPS-like syndrome in humans, and mutations in a gene encoding a protein kinase C (PRKCD) were discovered to cause a syndrome of lymphoproliferation, autoimmunity and natural killer cell defect. SUMMARY: The recent discoveries shed light on the molecular pathways governing lymphocyte death, proliferation and immune tolerance in humans. PMID- 24240294 TI - Bullying, adverse childhood experiences and use of texting to promote behavior change. AB - PURPOSE OF REVIEW: This article addresses three areas in which new research demonstrates the potential to impact the health of children and adolescents: bullying, adverse childhood experiences (ACEs) and texting to promote behavior change. RECENT FINDINGS: Recent research on bullying emphasizes its impact on children with chronic medical conditions, and highlights cyber bullying as a rising issue. ACEs are now recognized as risk factors for many health issues, particularly mental health problems. Text messaging is a promising new method to communicate with parents and adolescent patients. SUMMARY: Pediatric healthcare providers can help patients with chronic medical problems by addressing bullying at well child visits. Screening for ACEs may identify children at risk for mental health issues. Incorporating text messaging into clinical practice can improve disease management and patient education. PMID- 24240295 TI - Female athlete triad for the primary care pediatrician. AB - PURPOSE OF REVIEW: Female participation in athletics has increased significantly over the past several decades. For most young women, participation in sport fosters self-confidence, positive relationships with peers, and good physical health. However, with growing female representation in athletics, the sport community has become increasingly aware of the syndrome known as 'female athlete triad,' which describes the interplay between low energy availability (LEA), menstrual disturbances, and decreased bone mineral density (BMD). This review aims to discuss the definition and prevalence of the triad and prevention, detection, and treatment strategies. RECENT FINDINGS: Current research has elucidated the importance of identifying and treating the triad in young athletes, as adolescence is a critical time for bone development and failure to intervene can lead to long-term problems. First defined in 1992, full characterization of the triad in adolescents has been elusive because of difficulties in diagnosing low BMD in this population and reliance on self-report for menstrual disturbances and LEA. A 2007 reformulation of the triad incorporated research demonstrating that the full deleterious triad is rare and emphasized that its components exist on a spectrum. Removal of the stigma from the triad has the potential to allow earlier detection and treatment, thereby improving outcomes. SUMMARY: The female athlete triad is a problem with important long-term consequences. Education should be geared toward athletes as well as coaches, athletic trainers, school nurses, primary care providers, and others involved in female athletics to allow early identification and intervention. PMID- 24240297 TI - Effects of sodium chloride and polyethylene glycol on root-hair infection and nodulation of Vicia faba L. plants by Rhizobium leguminosarum. AB - The effects of sodium chloride and polyethylene glycol (PEG) on the interaction between Rhizobium leguminosarum strain 29d and root hairs of field bean (Vicia faba L. cv. Maris Bead) plants were investigated. Two levels each of NaCl (50 and 100 mol.m(-3)) and PEG (100 and 200 mol.m(-3)) were given at the time of root hair formation. Scanning electron microscopy showed rhizobial attachment and colonization on root-hair tips. Adhesion of rhizobia in both lateral and polar orientation, sometimes associated with microfibrils, occurred mainly in crooks at the root-hair tips; most of the infections also occurred here. Bacterial colonization and root-hair curling were both reduced by stress treatments. Polyethylene glycol but not NaCl significantly reduced root-hair diameter. The proportion of root hairs containing infection threads was reduced by 30% under NaCl and by 52% under PEG. The structure of some of the root hairs, epidermal and hypodermal cells, as seen by light microscopy in ultrasections, was distorted as a result of NaCl and PEG treatments; cells showed plasmolysis and folded membranes. After three weeks of treatment, both NaCl and PEG inhibited nodule number by about 50% and nodule weight by more than 60%. It is concluded that the root-hair infection process in Vicia faba is impaired by NaCl and PEG treatments and this in turn results in fewer nodules being produced. PMID- 24240298 TI - Intracellular compartmentation of two enzymes of berberine biosynthesis in plant cell cultures. AB - Out of the eight enzymes involved in the biosynthesis of the isoquinoline alkaloid berberine, at least, two enzymes, berberine bridge enzyme and (S) tetrahydroprotoberberine oxidase, are exclusively located in a vesicle with a specific gravity of rho=1.14 g.cm(-3) as shown by direct enzymatic assay as well as immunoelectrophoresis. Electronmicroscopic examination of the enzyme containing particulate preparation from Berberis wilsoniae var. subcaulialata cultured cells demonstrated that it is composed mainly of membranous vesicles. The protein composition of this preparation reveals the presence of only about 20 separable proteins, of which two major ones are berberine bridge enzyme and (S) tetrahydroprotoberberine oxidase. Incubation of these vesicles with the substrate (S)-reticuline in the presence and absence of S-adenosyl-L-methionine leads to the formation of a red product which was identified as dehydroscoulerine. If the cytoplasmic enzyme S-adenosyl-L-methionine:(S)-scoulerine-9-O-methyltransferase is added to the vesicle preparation in the presence of (S)-reticuline and S adenosyl-L-methionine, not dehydroscoulerine but columbamine, the immediate precursor of berberine is formed. Some of the quaternary alkaloids are located inside the vesicles; fusion of these vesicles leads to vacuoles containing the quaternary alkaloids. These vesicles are the first highly specific and unique compartment serving only alkaloid biosynthesis; they are found in members of four different plant families and in cell cultures as well as in differentiated tissue. PMID- 24240293 TI - Primary immunodeficiencies underlying fungal infections. AB - PURPOSE OF REVIEW: We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. RECENT FINDINGS: An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-gamma immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis. SUMMARY: CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID- 24240299 TI - Identification of phosphate granules occurring in seedling tissue of two palm species (Phoenix dactylifera and Washingtonia filifera). AB - Haustoria of two palm species, Phoenix dactylifera L. (date) and Washingtonia filifera (Lindl.) Wendl were carefully dissected from seeds, and the ultrastructural characteristics of the large, electron-opaque granules present in the cells of this tissue were compared using standard aldehyde and OsO4 fixations. In Washingtonia, the granules were smaller than those in date and were more variable in size and presence of non-opaque inclusions. All granules appeared to be membrane bounded although they often filled the bounded space. No protein, lipid, carbohydrate or tannins were found in the granules by standard staining procedures. The granules stained positively with two different metallic phosphate stains which contained either bismuth or lead. Energy dispersive X-ray microprobe analysis, done on aldehyde-fixed granules and those stained with both phosphate stains, confirmed the fact that phosphorus and calcium were present in the granules. The granules also bound the metallic stains as expected. All procedures consistently confirmed the presence of phosphate in the granules. The data are most consistent with the hypothesis that the granules are composed of polyphosphate. PMID- 24240300 TI - Kinetics of intracellular redistribution of phytochrome in Avena coleoptiles after its photoconversion to the active, far-red-absorbing form. AB - The kinetics of the intracellular redistribution of phytochrome (sequestering) in Avena sativa L. coleoptiles following a brief, saturating actinic pulse of red (R) light have been determined. Immunocytochemical labelling of phytochrome with monoclonal antibodies showed that at 22 degrees C sequestering can occur within 1 2 s from the onset of R irradiation and is dependent upon the continued presence of the far-red-absorbing form of phytochrome (Pfr). The initial rate, but not the final extent, of sequestering is reduced by lowering the temperature of the tissue to 1 degrees C. Sequestering at 22 degrees C appears to involve two distinct stages: (1) a rapid association of Pfr with putative binding sites initiates the sequestered condition, following which (2) these sites of sequestered phytochrome appear to aggregate. Neither of these two processes was affected by the cytoskeletal inhibitors colchicine or cytochalasin B. Phytochrome sequestering therefore resembles R-light-induced phytochrome pelletability with respect to kinetics, temperature sensitivity, and dependence upon the continued presence of Pfr in the cell. PMID- 24240301 TI - Chemotaxis and appetence of Paulsenella sp. (Dinophyta), an ectoparasite of the marine diatom Streptotheca thamesis Shrubsole. AB - The parasitic dinophyte, Paulsenella sp., is attracted chemotactically by its host, the centric diatom Streptotheca thamesis. Seemingly rather short-lived components of the diatom mucilage are involved in the process. These components are presumably secreted by the Golgi apparatus and pass the thecal slit between epi-and hypocingulum. Experiments with concanavalin A indicate that glucose and or mannose are constituents of the effective component, which is obviously not produced by egg cells, sperm cells and auxozygotes, since these stages do not attract the parasite. Plasmolysis inhibits secretion of the effective component. The readiness of the parasite to attack a host cell (its appetence) is light dependent: it is low in the dark period and increases after the beginning of the light period in cultures with a 14 h light/10 h dark regime. Endogenous rhythms of the parasite do not seem to be involved. In contrast, the attractiveness of the host is not influenced by the illumination. PMID- 24240302 TI - The specific activity of ribulose-1,5-bisphosphate carboxylase in relation to genotype in wheat. AB - The specific activity of ribulose-1,5-bisphosphate carboxylase (RuBPCase; EC 4.1.1.39) in crude extracts of leaves from euploid, amphiploid and alloplasmic lines of wheat fell into high or low categories (3.75 or 2.70 MUmol.mg(-1).min( 1), 30 degrees C). For the alloplasmic lines, where the same hexaploid nuclear genome was substituted into different cytoplasms, the specific activity of RuBPCase was consistent with the type of cytoplasm (high for the B and S cytoplasms and low for the A and D cytoplasms). There was no evidence from the euploid and amphiploid lines that small subunits encoded in different nuclear genomes influenced the specific activity. High specific activity was conferred by possession of the chloroplast genome of the B-type cytoplasm which encodes the large subunit of RuBPCase. All lines with a cytoplasm derived from the Sitopsis section of wheat, with the exception of Aegilops longissima and A. speltoides 18940, had RuBPCase with high specific activity. In contrast with the euploid lines of A. longissima, the alloplasmic line containing A. longissima cytoplasm from a different source had RuBPCase with high specific activity. The difference in specific activity found here in-vitro was not apparent in-vivo when leaf gas exchange was measured. PMID- 24240303 TI - The relationship between carbon-dioxide-limited photosynthetic rate and ribulose 1,5-bisphosphate-carboxylase content in two nuclear-cytoplasm substitution lines of wheat, and the coordination of ribulose-bisphosphate-carboxylation and electron-transport capacities. AB - Photosynthesis in two cultivars of Triticum aestivum was compared with photosynthesis in two lines having the same nuclear genomes but with cytoplasms derived from T. boeoticum. The in-vitro specific activity of ribulose-1,5 bisphosphate carboxylase (RuBPCase; EC 4.1.1.39) isolated from lines with T. boeoticum cytoplasm was only 71% of that of normal T. aestivum. By contrast, the RuBPCase activities calculated from the CO2-assimilation rate at low partial pressures of CO2, p(CO2), were the same for all lines for a given RuBPCase content. This indicates that both types of RuBPCase have the same turnover numbers in-vivo of 27.5 mol CO2.(mol enzyme)(-1).s(-1) (23 degrees ). The rate of CO2 assimilation measured at normal p(CO2), p a =340 MUbar, and high irradiance could be quantitatively predicted from the amount of RuBPCase protein. The maximum rate of RuBP regeneration could also predict the rate of CO2 assimilation at normal ambient conditions. Therefore, the maximum capacities for RuBP carboxylation and RuBP regeneration appear to be well-balanced for normal ambient conditions. As photosynthetic capacity declined with increasing leaf age, the capacities for RuBP carboxylation and RuBP regeneration declined in parallel. PMID- 24240304 TI - The use of a temperature-profiled position transducer for the study of low temperature growth in Gramineae : Equipment design and output interpretation. AB - A device is described for measuring linear extension of grass leaves during controlled cooling and heating of the growing region. The instrument was employed to investigate the sensitivity to temperature of the expanding third and fourth leaves of Lolium temulentum L. seedlings. Using a stepped temperature profile it was established that there was no lag in the response of growth rate to rapid changes in temperature below 16 degrees C. If cooling was continued to the point where growth ceased (1 degrees C) but no further, then rates of growth on rewarming were enhanced over the chilling range and reverted to the original rate at 20 degrees C. Cooling to successively lower subzero temperatures before rewarming abolished the hysteretic enhancement, progressively raised the temperature at which growth resumed and decreased the rate of extension until, at 5.3 degrees C, no recovery occurred. The temperature sensitivity of growth, measured as Q10, was essentially constant when cooling from 20 degrees C to 5 degrees C, with 5 degrees C-grown leaf tissue exhibiting a higher mean Q10 than tissue developed at 20 degrees C. The possible physiological significance of these data is discussed. PMID- 24240305 TI - Modification by gibberellin of the growth-temperature relationship in mutant and normal genotypes of several cereals. AB - High-resolution growth measurements were conducted using a linear variable displacement transformer in conjunction with a temperature-programmed meristem cooling collar. Chilling and rewarming profiles were determined for a range of Gramineae, in the presence and absence of varying concentrations of gibberellic acid (GA3). In wheat (Triticum aestivum L.) seedlings, the growth-constraining temperature (Pe) was progressively lowered by increasing GA3 concentration, with a difference of-4.8 degrees C between controls and material treated with 10(-4) M GA3. Dwarf-5 maize (Zea mays L.) seedlings had a higher Pe than tall segregates and the difference was markedly reduced by exposure to a saturating concentration of GA3. A similar effect was observed with Tanginbozu dwarf rice (Oryza sativa L.). The growth ratetemperature responses of Rht3 gibberellin-insensitive dwarf wheat seedlings were unaffected by GA3 and the Pe values for these segregates were around 5 degrees C higher than for normals. Slender (s1) barley (Hordeum vulgare L.) genotypes had Pe values of-7 degrees C, compared with +4 degrees C for wild-type material, and did not show positive hysteresis for growth rate during the rewarming phase. These studies indicate that GA3 modifies the thermal sensitivity of meristem function in Gramineae in a manner which enhances low temperature growth. PMID- 24240306 TI - The relationship between phosphate status and photosynthesis in leaves : Effects on intracellular orthophosphate distribution, photosynthesis and assimilate partitioning. AB - Photosynthesis, assimilate partitioning and intracellular distribution of orthophosphate (Pi) in barly (Hordeum vulgare L.) leaves were measured in plants grown with either 25, 1 or 0 mmol. 1(-1) nutrient phosphate supply. Phosphate deficiency resulted in a significant decrease in the leaf Pi, diminished rates of photosynthesis and a decrease in the sucrose/starch ratio in the leaves. Changes in the cytoplasmic Pi content were relatively small in comparison with the large variations in vacuolar Pi. The cytoplasmic Pi concentration was slightly higher in the leaves of plants grown at 25 mmol.l(-1) Pi than in those grown at 1 mmol.l(-1) Pi and was decreased in the phosphate-deficient plants in which photosynthesis was inhibited. With barley plants grown in phosphate-deficient media, very little, if any, Pi was present in the vacuole. All of the cellular Pi was in the cytoplasm. Barley, spinach (Spinacia oleracea L.) and soya (Glycine max L.) plants were grown to a comparative stage of phosphate deficiency as measured by leaf Pi levels. These species showed a uniform response to phosphate deficiency by increasing starch synthesis relative to sucrose but the accompanying limitation on photosynthetic capacity varied considerably among the species. Interspecific differences in assimilate partitioning between starch and sucrose were maintained over a wide range of Pi supply. PMID- 24240307 TI - The relationship between phosphate status and photosynthesis in leaves : Reversibility of the effects of phosphate deficiency on photosynthesis. AB - Spinach (Spinacia oleracea L.) and barley (Hordeum vulgare L.) were grown in hydroponic culture with varying levels of orthophosphate (Pi). When leaves were fed with 20 mmol.l(-1) Pi at low CO2 concentrations, a temporary increase of CO2 uptake was observed in Pi-deficient leaves but not in those from plants grown at 1 mmol.l(-1) Pi. At high concentrations of CO2 (at 21% or 2% O2) the Pi-induced stimulation of CO2 uptake was pronounced in the Pi-deficient leaves. The contents of phosphorylated metabolites in the leaves decreased as a result of Pi deficiency but were restored by Pi feeding. These results demonstrate that there is an appreciable capacity for rapid Pi uptake by leaf mesophyll cells and show that the effects of long-term phosphate deficiency on photosynthesis may be reversed (at least temporarily) within minutes by feeding with Pi. PMID- 24240308 TI - Acetylene reduction, H2 evolution and (15)N 2 fixation in the Alnus incana Frankia symbiosis. AB - Acetylene reduction, (15)N2 reduction and H2 evolution were measured in root systems of intact plants of grey alder (Alnus incana (L.) Moench) in symbiosis with Frankia. The ratios of C2H2: (15)N2 were compared with C2H2:N2 ratios calculated from C2H2 reduction and H2 evolution, and with C2H2:N2 ratios calculated from accumulated C2H4 production and nitrogen content. It was possible to calculate C2H2:N2 ratios from C2H2 reduction and H2 evolution because this source of Frankia did not show any hydrogenase activity. The ratios obtained using the different methods ranged from 2.72 to 4.42, but these values were not significantly different. It was also shown that enriched (15)N could be detected in the shoot after a 1-h incubation of the root-system. It is concluded that the measurement of H2 evolution in combination with C2H2 reduction represents a nondestructive assay for nitrogen fixation in a Frankia symbiosis which shows no detectable hydrogenase activity. PMID- 24240309 TI - Biomass production and nitrogen utilization by Alnus incana when grown on N2 or NH 4 (+) made available at the same rate. AB - A single clone of Alnus incana (L.) Moench was grown in a controlled-environment chamber. The plants were either inoculated with Frankia and fixed atmospheric nitrogen or were left uninoculated but received ammonium at the same rate as the first group fixed their nitrogen. Nitrogen fixation was calculated from frequenct measurements of acetylene reduction and hydrogen evolution. The diurnal variation of acetylene reduction was also taken into account. The relative efficiency of nitrogenase could be used in the calculations of fixed nitrogen since the Frankia used did not show any detectable hydrogenase activity. Alders fixing nitrogen developed more biomass, longer shoots, larger leaf areas and contained more nitrogen than alders receiving ammonium. In one experiment, almost all ammonium given to the non-nodulated alders was taken up and 15% of the nitrogen taken up was excreted. In the other experiment, 34% of the ammonium was left in the nutrient solution and 8% of the nitrogen taken up was excreted. Alders inoculated with Frankia did not excrete any detectable amount of nitrogen. It seems that the energy demand for nitrogen fixation is not so high that biomass production in alders is retarded. The symbiotic system of A. incana and Frankia seems to be more efficient in utilizing its nitrogen than non-symbiotic A. incana receiving ammonium. PMID- 24240310 TI - Exogenous polyamines alter membrane fluidity in bean leaves - a basis for potential misinterpretation of their true physiological role. AB - Changes in the rotational motion of paramagnetic and fluorescent lipid-soluble probes were used to assess the effects of putrescine, spermidine and spermine on the fluidity of microsomal membranes from primary leaves of bean (Phaseolus vulgaris L.). Surface probes were more strongly immobilized by physiological concentrations of the polyamines than probes that partitioned deep into the bilayer interior. Spermidine and spermine were more effective than putrescine at reducing membrane fluidity, and at equimolar concentrations, the polyamines and calcium had similar effects on the mobility of the membrane probes. Spermine had essentially equivalent effects on the fluidity of native membranes, heat denatured membranes and liposomes prepared from the total lipid extract of the membranes, indicating that polyamines associate with membrane lipid. These results raise the possibility that some of the physiological effects previously attributed to exogenously added polyamines could reflect membrane rigidification rather than a true physiological response. PMID- 24240311 TI - Cytokinin activation and redistribution of plasma-membrane ion channels in Funaria : A vibrating-microelectrode and cytoskeleton-inhibitor study. AB - I have investigated changes in electrical current across the plasma membrane that occur during cytokinin-induced bud formation in Funaria hygrometrica Hedw., using a non-intrusive vibrating microelectrode. Before cytokinin treatment the target caulonema cells have maximal inward current at the nuclear region. After cytokinin treatment inward current increases twofold along the length of the cell. Within minutes, however, current decreases at both the nuclear zone and the proximal end while increasing at the distal end of target cells, preceding and predicting the presumptive division site. Inward current at the distal end falls to resting levels after establishment of a bulging growth zone, and remains low around developing buds. This current is blocked by gadolinium nitrate, a Ca(2+) uptake inhibitor, indicating a Ca(2+) component of the current. The polarity of the target cells can be disrupted by microfilament inhibitors and cytokinin induced buds form over the nucleus, halfway along the length of the cell. I suggest that cytokinin activates plasma-membrane ion channels which are subsequently redistributed to the distal ends of target cells by a microfilament dependent process. Cytokinin-induced concentration of ion channels over presumptive bud sites may be envisioned to exert spatial control of cytoplasmic ion concentrations and stimulate bud formation by establishing a new growth zone, directing nuclear migration, and stimulating cell division. PMID- 24240312 TI - Evidence for the involvement of a UDP-glucose-dependent group translocator in sucrose uptake into vacuoles of storage roots of red beet. AB - Vacuoles isolated from the storage roots of red beet (Beta vulgaris L.) accumulate sucrose via two different mechanisms. One mechanism transports sucrose directly, and its rate is increased by the addition of MgATP. The other mechanism utilizes uridine diphosphate glucose (UDP-glucose) to synthesize and simultaneously transport sucrose phosphate and sucrose into the vacuole. This group translocation mechanism has also been found in sugarcane vacuoles. As in sugarcane, the beet group translocator does not require fructose 6-phosphate, nor is the latter substance transported into the vacuole. The uptake of UDP[(14)C]glucose in inhibited by high concentrations of osmoticum. PMID- 24240313 TI - The influence of a decrease in irradiance on photosynthetic carbon assimilation in leaves of Spinacia oleracea L. AB - When leaves of Spinacia oleracea L. were subjected to a decrease from a saturating to a limiting irradiance, photosynthetic carbon assimilation exhibited a pronounced lag. This comprised a postlower-illumination CO2 burst (Vines et al. 1982, Plant Physiol. 70, 629-631) and a slow increase in the rate of carbon assimilation to the new lower steady-state rate. The latter phenomenon was distinguishable from the former because it was present in leaves when photorespiration was inhibited by high concentrations of CO2 or by 2% O2. A lag which followed a decrease in irradiance was also evident in leaves of Zea mays in air or in isolated spinach protoplasts photosynthesising in high CO2. The lag was not stomatal in origin. The origin of the lag which followed the decrease in irradiance was investigated. Measurements of total (14)CO2 fixation and (14)C incorporated into sucrose during the transition in irradiance showed that sucrose synthesis displayed an overshoot during the transient which accounted for all of the carbon fixed during the first 90 s of the transition period. The behaviour of hexose phosphates in the intact leaf and in the cytosol was inconsistent with their supporting sucrose synthesis during the transient. It is concluded that the overshoot in sucrose synthesis imposes a drain on chloroplast intermediates which contributes to the temporary lag in the rate of carbon assimilation. PMID- 24240314 TI - Partial isotope fractionation during high-performance liquid chromatography of deuterium-labelled internal standards in plant hormone analysis: A cautionary note. AB - Deuterium-labelled indole-3-acetic acid, abscisic acid and phthalimido-1 aminocyclopropane-1-carboxylic acid were found to separate from the unlabelled compounds on reverse-phase high-performance liquid chromatography (HPLC). A similar separation was found for the methyl esters of these compounds on normal phase HPLC. Such separations may lead to substantial errors when these compounds are used as internal standards for quantitation by gas chromatography-mass spectrometry/selective ion detection, unless the complete chromatographic peaks are collected. PMID- 24240315 TI - Evaluation of surgical conditions during laparoscopic surgery in patients with moderate vs deep neuromuscular block. AB - BACKGROUND: The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed. METHODS: Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1-2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1-2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images. RESULTS: Mean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1-3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average kappa statistic 0.05). CONCLUSIONS: Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients' peri- and postoperative cardiorespiratory conditions. Trial registration The study was registered at clinicaltrials.gov under number NCT01361149. PMID- 24240316 TI - Host genomic HIV restriction factors modulate the response to dendritic cell based treatment against HIV-1. AB - Host genome is still poorly investigated in the context of vaccine or immunotherapy, however recently findings emphasized that it may affect the response to those treatments. In our retrospective study we evaluated the effect of HIV-1 genetic restriction factors on the response to dendritic cell (DC)-based immunotherapy in a Brazilian cohort of HIV positive (HIV+) patients that underwent a phase I clinical trial in 2004. Genomic DNA from 18 HIV+ individuals that underwent DC-based immunotherapy was analyzed for selected polymorphisms known to be associated with susceptibility to HIV-1 infection and/or AIDS progression. Allelic and genotypic distribution of the 22 polymorphisms was evaluated considering the response to the treatment. The rs11884476 SNP in PARD3B resulted associated with good response to immune treatment according to an over dominant model. Even if functional effect of this variation is still unknown, our data suggested that it could play a role in the control of viral replication. Our findings, being aware of the limitation represented by the small number of subjects analyzed, suggest that genetic factors involved in AIDS progression could affect the response to immunotherapy, reinforcing the idea that deeper investigation on host genetic variations will be fundamental for a rational vaccine development. PMID- 24240317 TI - Occurrence and distribution of antibiotic-resistant bacteria and transfer of resistance genes in Lake Taihu. AB - The overuse of antibiotics has accelerated antibiotic resistance in the natural environment, especially fresh water, generating a potential risk for public health around the world. In this study, antibiotic resistance in Lake Taihu was investigated and this was the first thorough data obtained through culture dependent methods. High percentages of resistance to streptomycin and ampicillin among bacterial isolates were detected, followed by tetracycline and chloramphenicol. Especially high levels of ampicillin resistance in the western and northern regions were illustrated. Bacterial identification of the isolates selected for further study indicated the prevalence of some opportunistic pathogens and 62.0% of the 78 isolates exhibited multiple antibiotic resistance. The presence of ESBLs genes was in the following sequence: bla(TEM) > bla(SHV) > bla(CTMX) and 38.5% of the isolates had a class I integrase gene. Of all tested strains, 80.8% were able to transfer antibiotic resistance through conjugation. We also concluded that some new families of human-associated ESBLs and AmpC genes can be found in natural environmental isolates. The prevalence of antibiotic resistance and the dissemination of transferable antibiotic resistance in bacterial isolates (especially in opportunistic pathogens) was alarming and clearly indicated the urgency of realizing the health risks of antibiotic resistance to human and animal populations who are dependent on Lake Taihu for water consumption. PMID- 24240318 TI - Mathematical ecology analysis of geographical distribution of soybean-nodulating Bradyrhizobia in Japan. AB - We characterized the relationship between the genetic diversity of indigenous soybean-nodulating bradyrhizobia from weakly acidic soils in Japan and their geographical distribution in an ecological study of indigenous soybean rhizobia. We isolated bradyrhizobia from three kinds of Rj-genotype soybeans. Their genetic diversity and community structure were analyzed by PCR-RFLP analysis of the 16S 23S rRNA gene internal transcribed spacer (ITS) region with 11 Bradyrhizobium USDA strains as references. We used data from the present study and previous studies to carry out mathematical ecological analyses, multidimensional scaling analysis with the Bray-Curtis index, polar ordination analysis, and multiple regression analyses to characterize the relationship between soybean-nodulating bradyrhizobial community structures and their geographical distribution. The mathematical ecological approaches used in this study demonstrated the presence of ecological niches and suggested the geographical distribution of soybean nodulating bradyrhizobia to be a function of latitude and the related climate, with clusters in the order Bj123, Bj110, Bj6, and Be76 from north to south in Japan. PMID- 24240319 TI - Integrating protein-protein interaction networks with phenotypes reveals signs of interactions. AB - A major objective of systems biology is to organize molecular interactions as networks and to characterize information flow within networks. We describe a computational framework to integrate protein-protein interaction (PPI) networks and genetic screens to predict the 'signs' of interactions (i.e., activation inhibition relationships). We constructed a Drosophila melanogaster signed PPI network consisting of 6,125 signed PPIs connecting 3,352 proteins that can be used to identify positive and negative regulators of signaling pathways and protein complexes. We identified an unexpected role for the metabolic enzymes enolase and aldo-keto reductase as positive and negative regulators of proteolysis, respectively. Characterization of the activation-inhibition relationships between physically interacting proteins within signaling pathways will affect our understanding of many biological functions, including signal transduction and mechanisms of disease. PMID- 24240320 TI - Deciphering laminar-specific neural inputs with line-scanning fMRI. AB - Using a line-scanning method during functional magnetic resonance imaging (fMRI), we obtained high temporal (50-ms) and spatial (50-MUm) resolution information along the cortical thickness and showed that the laminar position of fMRI onset coincides with distinct neural inputs in rat somatosensory and motor cortices. This laminar-specific fMRI onset allowed us to identify the neural inputs underlying ipsilateral fMRI activation in the barrel cortex due to peripheral denervation-induced plasticity. PMID- 24240321 TI - A holidic medium for Drosophila melanogaster. AB - A critical requirement for research using model organisms is a well-defined and consistent diet. There is currently no complete chemically defined (holidic) diet available for Drosophila melanogaster. We describe a holidic medium that is equal in performance to an oligidic diet optimized for adult fecundity and lifespan. This holidic diet supports development over multiple generations but at a reduced rate. Over 7 years of experiments, the holidic diet yielded more consistent experimental outcomes than did oligidic food for egg laying by females. Nutrients and drugs were more available to flies in holidic medium and, similar to dietary restriction on oligidic food, amino acid dilution increased fly lifespan. We used this holidic medium to investigate amino acid-specific effects on food-choice behavior and report that folic acid from the microbiota is sufficient for Drosophila development. PMID- 24240322 TI - HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics. AB - We present a liquid chromatography-mass spectrometry (LC-MS)-based method permitting unbiased (gene prediction-independent) genome-wide discovery of protein-coding loci in higher eukaryotes. Using high-resolution isoelectric focusing (HiRIEF) at the peptide level in the 3.7-5.0 pH range and accurate peptide isoelectric point (pI) prediction, we probed the six-reading-frame translation of the human and mouse genomes and identified 98 and 52 previously undiscovered protein-coding loci, respectively. The method also enabled deep proteome coverage, identifying 13,078 human and 10,637 mouse proteins. PMID- 24240323 TI - Imaging appearances and clinical outcome following sacrectomy and ilio-lumbar reconstruction for sacral neoplasia. AB - OBJECTIVE: Sacrectomy and ilio-lumbar reconstruction is an uncommonly performed complex surgical procedure for the treatment of sacral neoplasia. There are many challenges in the post-operative period including the potential for tumor recurrence, infection, and construct failure. We present our experience of this patient cohort and describe the complications and imaging appearances that can be encountered during the follow-up period. MATERIALS AND METHODS: Retrospective review of our Orthopaedic Oncology database was undertaken which has been collected over a 30-year period to identify patients that had undergone sacrectomy and ilio-lumbar reconstruction. Pre and post-operative imaging including radiographs, CT, and MRI was reviewed. These were viewed by two experienced musculoskeletal radiologists with consensus opinion if there was disagreement over the imaging findings. Data regarding patient demographics, tumor type, and dimensions was collected. Serial review of radiographs, CT, and MRI was performed to assess implant position and integrity, strut graft position and union, and for the presence of recurrence within the surgical bed. RESULTS: Five male and two female patients (mean age 36 years, age range 15-54 years) were treated with this procedure. Histological diagnoses included chordoma, chondrosarcoma, osteosarcoma, and spindle cell sarcoma. Mean maximal tumor size on pre-operative imaging was 10.7 cm (range, 6-16 cm). Post-operative follow-up ranged from 10-46 months. A total of 76 imaging studies were reviewed. Commonly identified complications included vertical rod and cross-connector fracture and screw loosening. Fibula strut graft non-union and fracture was also evident on imaging review. Two patients demonstrated disease recurrence during the follow-up period. CONCLUSIONS: This study demonstrates the spectrum and frequency of complications that can occur following sacrectomy and ilio-lumbar reconstruction for sacral neoplasia. PMID- 24240324 TI - Analysis of DNA size, content and cell cycle in leaves of Napier grass (Pennisetum purpureum Schum.). AB - Mesophyll cell nuclei isolated from leaves of Pennisetum purpureum were analysed by flow cytometry to determine the nuclear DNA content and the percentage of cells in different phases of the cell cycle. Samples taken from base, middle and tip regions of leaves 2 to 8 (leaf 1, which was adjacent to the meristem, was too small to sample) showed no significant differences in the amount of DNA per G1 nucleus due to either age or position. The average amount of DNA per G1 nucleus was 5.78 pg. Although the majority of cells for each sample were in G1, samples taken from older leaves had higher percentages of cells in G2 and S phases. More specifically, base and middle regions of older leaves had a higher percentage of cells in G2 than all three positions in younger leaves. Electrophoretic analysis of nuclear DNA from leaves 2 to 7 showed no evidence of degradation or difference in fragment size for any sample or position. This study was compared to previous work on the relationship between leaf age and embryogenic competence in Pennisetum purpureum. The results suggest that changes in the cell cycle, and/or a loss or fragmentation of the nuclear DNA, are not responsible for loss of embryogenic competence in mature leaf tissue. PMID- 24240325 TI - Chromosome studies of progenies of tetraploid female rainbow trout. AB - Nine induced tetraploid females were artificially inseminated by UV-irradiated sperm collected from diploid males, in order to induce the gynogenetic development of their ova. Most of the resulting embryos were diploid (or minor aneuploids). Several gynogenetic tetraploids, likely to issue from unreduced ova, were also detected in these progenies. The same females fertilized by normal sperm of diploid males gave a majority of triploids and several pentaploids, while the fertilization by normal sperm of tetraploid males gave rise to a majority of tetraploids and one hexaploid. The same crosses, after the eggs had been heat-shocked to double the maternal genetic contribution, yielded about three-quarters pentaploids and one quarter haploids (normal sperm of diploids), or three-quarters hexaploids and one quarter diploids (normal sperm of tetraploids). These haploids and diploids are likely to result from androgenesis. PMID- 24240326 TI - Quantitative cytology of the egg and central cell of Plumbago zeylanica and its impact on cytoplasmic inheritance patterns. AB - The egg and central cells of Plumbago zeylanica have an average volume of 543,000 MUm(3) and 2,560,000 MUm(3) respectively, with surface areas of 38,600 MUm(2) and 154,000 MUm(2). The egg contains an average of 39,900 mitochondria and 730 plastids. The majority of the plastids are perinuclear (> 60%) with less than 40% in lateral areas or near the filiform apparatus. After fertilization, the number of maternal organelles exceeds paternal organelles by a ratio of 1?1,000 for mitochondria and 1?54 for plastids. The central cell contains an average of 178,700 mitochondria and 1,840 plastids. After fertilization, these organelles far exceed the number of sperm organelles transmitted, by a ratio of approx. 1?4,000 for plastids and 1?820 for mitochondria. Biparental inheritance of plastids in the embryo is possible, but not favored; the only comparable data in Oenothera and Impatiens reveals that biparental inheritance is possible in up to 1?24 ratios. Plants lacking biparental plastid inheritance do not contain plastids in the sperm, and thus the presence of even few sperm plastids may result in expression. The number of paternal mitochondria transmitted into the central cell is greater than that transmitted into the egg as the result of preferential fertilization with the mitochondrion-rich dimorphic sperm cell, although the ratio of paternal to maternal mitochondria is 1?1,000 in the egg and 1?820 in the central cell. The similarity in these ratios suggests that there is a critical dosage of mitochondria that is permissible within the zygotic and endospermatic lineages. This may represent either: (1) a maximum permissible value to prevent expression of paternal mitochondrial genome, (2) a minimum ratio required in order to permit recombination of maternal and paternal mitochondrial genomes, or (3) a cytoplasmic genome balance number. PMID- 24240327 TI - In vitro selection of alfalfa plants resistant to Fusarium oxysporum f. sp. medicaginis. AB - From two lines of Medicago sativa characterized by a high regeneration capability, calli resistant to culture filtrate of Fusarium oxysporum f. sp. medicaginis have been selected. In these calli regeneration capability was greatly reduced and only one plant per callus was recovered. Regenerated plants have been evaluated for resistance to culture filtrate and for in vivo resistance to the pathogen. Three plants out of eight were resistant to the fungus and a high correlation between resistance to culture filtrate and in vivo resistance was observed. PMID- 24240328 TI - High molecular weight glutenin subunit variation in Triticum turgidum var. dicoccum. AB - Variation in high molecular weight (HMW) glutenin subunit composition among 167 accessions of dicoccum wheat (Triticum turgidum L. var. dicoccum Schrank) of diverse origins was investigated using one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). A total of 20 alleles were identified, and 9 of them were found to be different from those previously detected by Payne and Lawrence (1983 b) in hexaploid wheat (Triticum aestivum L.). The newly discovered alleles enhance the genetic variability available to improve the industrial quality of wheats and some of them may facilitate basic research on the relationship of industrial quality with HMW glutenin subunit number. The novel variants include a GLU-A1 encoded subunit which has higher molecular mass than any other so far described in tetraploid and hexaploid wheats, and a 'null' GLU-B1 allele. Dicoccums containing neither GLU-A1- nor GLU B1-encoded subunits were also identified. A comparison of the mean number of HMW glutenin subunits contained in various primitive and modern domesticated wheats of different ploidy levels and the identification of wheats containing no HMW glutenin subunits suggest that the occurrence of 'null' GLU-1 alleles in these species depends on chance rather on an inherent tendency on the part of modern polyploid wheats to suppress the activity of redundant GLU-1 genes. PMID- 24240329 TI - Nodulation and nitrogen fixation mutants of pea, Pisum sativum. AB - The 36 mutants which did not nodulate and 24 mutants which formed inefficient nodules with no or very low acetylene reduction activity were isolated among 86,000 M2-seedlings of 'Finale' pea, Pisum sativum L., after treatment with chemical mutagens. One mutant was found for approximately every 50 chlorophyll mutants. Most mutations were induced by ethyl methanesulfonate; some by diethyl sulfate, ethyl nitrosourea and acidified sodium azide. Putative mutants were selected as nitrogen deficient plants, yellowing from the bottom and up, when M2 seedlings were grown in sand with a Rhizobium mixture and PK fertilizer. The mutants were verified in the M3 generation by acetylene reduction assay on intact plants. PMID- 24240330 TI - Inheritance and expression of NAD(P)H nitrate reductase in barley. AB - NADH-specific and NAD(P)H bispecific nitrate reductases are present in barley (Hordeum vulgare L.). Wild-type leaves have only the NADH-specific enzyme while mutants with defects in the NADH nitrate reductase structural gene (nar1) have the NAD(P)H bispecific enzyme. A mutant deficient in the NAD(P)H nitrate reductase was isolated in a line (nar1a) deficient in the NADH nitrate reductase structural gene. The double mutant (nar1a;nar7w) lacks NAD(P)H nitrate reductase activity and has xanthine dehydrogenase and nitrite reductase activities similar to nar1a. NAD(P)H nitrate reductase activity in this mutant is controlled by a single codominant gene designated nar7. The nar7 locus appears to be the NAD(P)H nitrate reductase structural gene and is not closely linked to nar1. From segregating progeny of a cross between the wild type and nar1a;nar7w, a line was obtained which has the same NADH nitrate reductase activity as the wild type in both the roots and leaves but lacks NADPH nitrate reductase activity in the roots. This line is assumed to have the genotype Nar1Nar1nar7nar7. Roots of wild type seedlings have both nitrate reductases as shown by differential inactivation of the NADH and NAD(P)H nitrate reductases by a monospecific NADH-nitrate reductase antiserum. Thus, nar7 controls the NAD(P)H nitrate reductase in roots and in leaves of barley. PMID- 24240332 TI - Salt tolerance through increased vigor in a flax line (STS-II) selected for salt tolerance in vitro. AB - Progeny of a flax (Linum usitatissimum L. cv "McGregor") plant, regenerated from a cell line selected in vitro for salt tolerance (designated STS-II) was tested for its performance over two generations in normal and in saline soil against its parent variety. Germination, seedling height, flowering, seed set and seed yield in controlled greenhouse conditions were recorded. The putative salt tolerant line was superior in saline soil for all parameters measured, indicating that the mechanism selected in cells in vitro was also active in whole plants, and that the trait is genetically stable and seed transmitted. Unexpectedly, the STS-II line was also superior in the normal, non-stressed soil, indicating that the selected trait is not limited to salt tolerance specifically, suggesting a more general mechanism, such as a general increase in vigor. PMID- 24240331 TI - Asymmetric hybridization in Nicotiana by fusion of irradiated protoplasts. AB - Mesophyll protoplasts of a kanamycin-resistant, nopaline-positive Nicotiana plumbaginifolia seed line were inactivated by gamma-irradiation and electrically fused with unirradiated mesophyll protoplasts of N. tabacum. Hybrids were selected on kanamycin and regenerated. Genetic material from N. plumbaginifolia was detected in these plants by the following criteria: (1) morphology, (2) esterase isozyme profiles, and (3) the presence of nopaline in leaf extracts. All of the plants regenerated were morphologically more similar to N. tabacum than to N. plumbaginifolia, and many were indistinguishable from N. tabacum. It was found that 37 plants displayed one or two esterases characteristic of N. plumbaginifolia in addition to a full set of esterases from N. tabacum. Based on their esterases, we have classified these plants as somatic hybrids. However, irradiation has clearly reduced the amount of N. plumbaginifolia genetic material that they retain; 24 plants were found that had only N. tabacum esterases but that produced nopaline and were kanamycin resistant. Genomic DNA from several of these plants was probed by Southern blotting for the presence of the authentic neomycin phosphotransferase gene (kanamycin-resistance gene) - all were found to contain the gene. These plants were classified as asymmetric hybrids. Finally, 25 plants were regenerated that were kanamycin sensitive, negative for nopaline, and contained only N. tabacum esterases. All of the regenerated plants, including this final category, were male sterile. As transferring the N. plumbaginifolia cytoplasm to an N. tabacum nuclear background results in an alloplasmic form of male sterility, all of the plants regenerated in this study appear to be cybrids irrespective of their nuclear constitution. Chromosome analysis of the asymmetric hybrids showed that most of them contained one more chromosome than is normal for N. tabacum. The somatic hybrids examined all had several additional chromosomes. Although male sterile, the asymmetric hybrids were female fertile to varying degrees and were successfully backcrossed with N. tabacum. Analysis of the resultant F1 progeny indicated that the kanamycin-resistance gene from N. plumbaginifolia is partially unstable during meiosis, as would be expected for factors inherited on an unpaired chromosome. PMID- 24240333 TI - Somaclonal variation versus chemically induced mutagenesis in tomato (Lycopersicon esculentum L.). AB - A comparison was made of the type and frequency of mutational events found in the progeny of tomato plants regenerated after one passage in vitro with those induced by chemical mutagenesis with ethyl methane sulphonate. Several mutants were recovered in the progeny of regenerated and mutagenized plants of two cultivars of tomato. They can be grouped into the following categories: seedling lethality, male sterility, resistance to Verticillium, short stature, change in number of lateral shoots or in leaf shape. The results indicate that the two sources of variability differ in their effect, changing the spectrum and frequency of the mutants as well as, at least in some cases, their pattern of segregation. PMID- 24240334 TI - The endosperm seed protein Solin: biochemical characterization, induction by ABA and species-specific subunits. AB - Comparison of endosperm storage protein sub units from single seeds of 19 Solanum species was done by isoelectric focusing. Species-specific profiles of the subunits were evident and species relationships within a taxonomic series could be delineated. The identification of both intraspecific and interspecific hybrid seed may be possible from Solin IEF subunit profiles. The glutelin nature of the protein was unusual for a dicotyledon genus. We named this major endosperm protein complex "Solin". Solin was found in developing seeds with embryos at the heart stage, 16 to 18 days after pollination. Seeds excised at the globular stage responded to the addition of ABA and synthesized Solin. This is the first report of the induction of seed protein in endosperm cells of Solanum. PMID- 24240335 TI - Selection of Daucus cybrids based on metabolic complementation between X irradiated D. capillifolius and iodoacetamide-treated D. carota by somatic cell fusion. AB - Protoplasts of Daucus capillifolius isolated from a suspension culture (chromosome number above 60) were X-irradiated over lethal dose (60 krad) just prior to fusion. Protoplasts from D. carota cell line (chromosome number 17) were treated with 15 mM iodoacetamide and fused with the X-irradiated protoplasts. Putative cybrid plants were regenerated on Murashige and Skoog medium (MS) lacking 2,4-D. The regenerated plants possessed chromosome numbers of 17 (2n-1) or 34 (4n-2) and an identical leaf morphology to D. carota. Their mitochondrial DNAs (mtDNAs) were analysed with restriction endonucleases. Novel restriction fragments, not present in mtDNA digests from both parents, were observed in mtDNAs of regenerated plants. These results indicate successful formation of cybrids between D. capillifolius and D. carota by protoplast fusion. PMID- 24240336 TI - Expected early genetic gain from selection for milk yield in dairy cattle. AB - A matrix program to predict short term genetic gain from single trait selection for milk yield was developed. Rate of genetic gain was calculated as the annual change in the mean breeding value of all producing females. Several parameters sets representing various selection policies were used to examine situations pertinent to dairy populations of the United States. Approach to the asymptotic rates of genetic gain within the model varied with the choice of parameters, but even with consistent selection policies, predicted total genetic gain in the first 10 years was only half of the expected from classical theory. Considerable year to year variation in the rate of gain occurred. Early gains were more dependent on female selection decisions than gains during the steady state. In a two-phase model, the approach to the linear rate of gain in the second phase was accelerated by starting with an ongoing improvement program, but considerable delays still existed. Selection for sex- limited traits such as milk yield, which require pedigree selection and a waiting time for progeny test results reached asymptotic rates more slowly than previously assumed. PMID- 24240337 TI - Analysis of the Brassica oleracea genome by the generation of B. campestris oleracea chromosome addition lines: characterization by isozymes and rDNA genes. AB - This study aimed at generating chromosome addition lines and disclosing genome specific markers in Brassica. These stocks will be used to study genome evolution in Brassica oleracea L., B. campestris L. and the derived amphidiploid species B. napus L. B. campestris-oleracea monosomic and disomic chromosome addition plants were generated by crossing and backcrossing the natural amphidiploid B. napus to the diploid parental species B. campestris. The pollen viability of the derived sesquidiploid and hyperploid ranged from 63% to 88%, while the monosomic and disomic addition plants had an average pollen fertility of 94% and 91%, respectively. The addition lines were genetically characterized by genome specific markers. The isozymes for 6PGD, LAP, PGI and PGM, and rDNA Eco RI restriction fragments were found to possess the desired genome specificity. Duplicated loci for several of these markers were observed in B. campestris and B. oleracea, supporting the hypothesis that these diploid species are actually secondary polyploids. A total of eight monosomic and eight disomic addition plants were identified and characterized on the basis of these markers. Another 51 plants remained uncharacterized due to the lack of additional markers. rDNA genes were found to be distributed in more than one chromosome, differing in its restriction sites. Intergenomic recombination for some of the markers was detected at frequencies between 6% and 20%, revealing the feasibility of intergenomic gene transfer. PMID- 24240338 TI - The inheritance of seed peroxidases of wheat and rye: further data. AB - Further data on the inheritance of seed peroxidases of hexaploid wheat (Triticum aestivum L.) and rye (Secale cereale L.) have been obtained from the genetic analysis of several progenies of both species. Additional data on the inheritance and the chromosomal location and linkage have been obtained for peroxidases of wheat embryo and rye endosperm. The general presence of null alleles in peroxidase loci has been confirmed in both species. In addition to simple monogenic inheritance, epistatic segregations have been observed in both species. These epistatic segregations again suggest the presence of "regulatory" genes controlling the expression of individual peroxidases in both species and also the existence of several duplicate homoeologous genes in wheat. Known linkage relationships have been confirmed and new ones are indicated. Loci for embryo wheat peroxidases seem to be in chromosomes of the homoeology group 3. The rye endosperm ones should be in chromosome 7R, although it is hypothesized that a duplication of gene EPer1 is located in chromosomes 4R and 7R. PMID- 24240339 TI - Molecular analysis of the mitochondrial genome of Helianthus annuus in relation to cytoplasmic male sterility and phylogeny. AB - A circular supercoiled mitochondrial DNA plasmid P1 (1.45 kb) is shown in both normal fertile plants of Helianthus annuus, and some cytoplasmic male sterile lines (CMS A and CMS P). In contrast, no plasmid is found in some other types of CMS C, I, B and K. A circular supercoiled DNA (P2) of higher molecular weight (1.8 kb) is observed in CMS F. The mitochondrial plasmid P1 was cloned, nick translated and hybridized with native mitochondrial DNA from different lines of male fertile, CMS or wild Helianthus. No sequence homology has been detected between plasmid DNA P1 and high molecular weight mitochondrial DNA in any line examined. A slight hybridization occurs between plasmids P1 and P2. Thus, there is no apparent relationship between mitochondrial plasmid DNA and CMS or Helianthus species. On the contrary, each Helianthus CMS and male fertile strain can be characterized by digestion fragment patterns (Sal I and Bgl I). Analysis of mitochondrial DNA from wild Helianthus strains indicated a relation between some CMS and the strain from which they were maternally derived, as for example CMS I and H. annuus ssp lenticularis and CMS F and H. petiolaris fallax. On the basis of restriction endonuclease patterns, a CMS phylogenic tree is proposed which illustrates a molecular polymorphism in the mitochondrial genome of Helianthus. PMID- 24240340 TI - Sequence of the 18S-5S ribosomal gene region and the cytochrome oxidase II gene from mtDNA of Zea diploperennis. AB - The coding and flanking sequences of the 18S-5S ribosomal RNA genes and the cytochrome oxidase subunit II gene of Zea diploperennis mitochondrial DNA have been determined and compared to the corresponding sequences of normal maize (Zea mays L.) Both length and substitution mutations are found in the coding region of the 18S rRNA gene, whereas only one substitution mutation is found in the coding region of cytochrome oxidase II. Sequence divergence between maize and Zea diploperennis is about one-tenth of that between wheat and maize. The rate of nucleotide divergence by base substitution is less for plant mitochrondrial genes than for comparable genes in animal mitochondria. PMID- 24240341 TI - Stability of self-incompatibility systems. AB - Multi-locus self-incompatibility systems offer few obvious adaptive advantages to the species possessing them. However, the gametophytic system's independent gene action allows the separate genes in a two gene system to behave as if they were individually not involved in a systematic disruption of panmixia. Under such circumstances, fixation of one of the two genes is readily obtained if an allele possesses a selective advantage. The resulting single gene system (the classic Nicotiana system) is then resistant to disruption, except by genes which allow selfing, which rapidly reach fixation. PMID- 24240342 TI - Selection for components related to body composition in mice: direct responses. AB - Replicated within full-sib family single-trait selection was conducted for 10 generations in mice for (1) high or low 12-week epididymal fat pad percentage (100 x epididymal fat pad weight/body weight) or (2) high or low 12-week hind carcass percentage (100 x hind carcass weight/body weight). Pooled realized heritabilities based on high, low and divergent selection were 0.66+/-0.09, 0.65+/-0.13 and 0.66+/-0.05 for epididymal fat pad percentage and 0.48+/-0.08, 0.33+/-0.08 and 0.40+/-0.04 for hind carcass percentage. The pooled realized genetic correlation (rG R) between epididymal fat pad percentage and hind carcass percentage based on divergence was -0.67+/-0.04. Other estimates of (rG R) were: epididymal fat pad percentage with body weight (0.57+/-0.05); epididymal fat pad percentage with epididymal fat pad weight (1.17+/-0.05); hind carcass percentage with body weight (-0.61+/-0.09); hind carcass percentage with hind carcass weight (-0.05+/-0.11). Indirect measures of fat and lean tissue percentages were highly heritable, and (rG R) between them would be desirable from the standpoint of analogous types of traits in livestock. In the same context, undesirable (rG R)'s were found between epididymal fat pad percentage and body weight and between hind carcass percentage and body weight. PMID- 24240343 TI - Aneuploid and alloplasmic lines as tools for the study of nuclear and cytoplasmic control of culture ability and regeneration of scutellar calli from common wheat. AB - Twenty four B genome aneuploid lines (di-telosomics, nullisomic-tetrasomics and tetrasomics) of Triticum aestivum cv 'Chinese Spring' were used in an analysis of the culture ability and regeneration capability of scutellar calli. Several correlations were found between the presence or absence of specific chromosomes and chromosomal arms of the B genome of common wheat and the growth and differentiation capabilities of these calli. The rate of callus growth decreased only when the long arm of chromosome 6B was not present. The absence of chromosomes 3B and 7B did not result in an apparent change in morphogenetic capability, while the absence of other B genome chromosomes was significantly correlated to changes in the frequency of calli that regenerated plants. The presence of the short arm of chromosome 1B was negatively correlated with regeneration, whereas its long arm is probably required to counteract this effect and to maintain the normal ratio of regeneration. The presence of the chromosomal arm 2BS seemed to be essential for differentiation to shoots. In the absence of the short arms of chromosomes 4B and 5B, the rate of regeneration was slightly reduced. In the absence of the long arm of chromosome 6B there was a marked reduction of the ability of scutellar calli to regenerate plants. The use of additional aneuploid lines belonging to homoeologous group 6 revealed that only calli derived from lines having chromosome 6D in their complement regenerated plants similarly to the euploid control. Culture ability and regeneration capability were also analysed with alloplasmic lines of T. aestivum cv 'Chris'. The lines were derived from five species, representing plasma-types of different phylogenetic distances from plasma-type B of T. aestivum. The results showed that when the endogenous cytoplasm (B-type) was exchanged with T. timopheevii cytoplasm (G-type) there was a significant increase in the regeneration of shoots from the scutellar calli. PMID- 24240344 TI - Subunits of tetrameric alpha-amylase inhibitors of Hordeum chilense are encoded by genes located in chromosomes 4H(ch) and 7H (ch.). AB - Three proteins (components 1, 2, and 4) of the non-prolamin, 70% ethanol soluble fraction from the endosperm of Hordeum chilense have been identified as putative subunits of the tetrameric inhibitors active against insect alpha-amylases. In experiments carried out with the synthetic alloploid Tritordeum (H. chilense x Triticum turgidum conv. durum), previously described proteins from T. turgidum, designated CM2, CM3 and CM 16, have been also identified as subunits of alpha amylase inhibitors. Genes for components 1 and 4 of H. chilense have been located in chromosomes 4H(ch) and 7H(ch), based on the analysis of H. chilense-T.turgidum addition lines. Subunits of the inhibitors from wheat and from cultivated barley had been previously assigned to chromosomes of the same homoeology groups. PMID- 24240345 TI - Inheritance of resistance to the cowpea aphid in cowpea. AB - Inheritance of resistance to cowpea aphid, Aphis craccivora Koch, in three resistant cultivars of cowpea, Vigna unguiculata (L.) Walp, was studied. The parents, F1 and F2 population were grown in an insect-proof screenhouse. Each 3 day-old seedling was infested with 10 apterous adult aphids. Seedling reaction was recorded when the susceptible check was killed. The segregation data revealed that the resistance of ICV11 and TVU310 is governed by single dominant genes. All the F2 seedlings of the cross ICV10xTVU310 were resistant, indicating that they have the same gene for resistance. However, the F2 populations from the crosses ICV10xICV11 and ICV11xTVU310 segregated in a ratio of 15?1, indicating that the dominant genes in ICV11 and TVU310 are non-allelic and independent of each other. The resistance gene of ICV10 and TVU310 is designated as Ac1 and that of ICV11 as Ac2. PMID- 24240346 TI - A universal reference karyotype in rye, Secale cereale L. AB - Haploid, dihaploid and tetrahaploid rye plants of the variety 'Petka' have been produced to establish a homozygous genotype and karyotype. The morphology, karyotypic characteristics and the metaphase I chromosome behaviour are described demonstrating the utility of the material as a universal standard tester in rye cytogenetics. Clones of several ploidy levels are maintained by long-term in vitro sprout culture. They are available for international testing. Sexual propagation of the clones is possible using a heat treatment procedure to break the self-incompatibility of the homozygotes. PMID- 24240347 TI - Wheat storage proteins: diversity of HMW glutenin subunits in wild emmer from Israel : 1. Geographical patterns and ecological predictability. AB - The diversity of HMW glutenin subunits in the tetraploid wild progenitor of wheat, Triticum turgidum var. dicoccoides was studied electrophoretically in 231 individuals representing 11 populations of wild emmer from Israel. The results show that (a) The two HMW glutenin loci, Glu-A1 and Glu-B1, are rich in variation, having 11 and 15 alleles, respectively, (b) Genetic variation in HMW glutenin subunits is often severely restricted in individual populations, supporting an island population genetic model, (c) Significant correlations were found between glutenin diversity and the frequencies of specific glutenin alleles and physical (climate and soil) and biotic (vegetation) variables. Our results suggest that: (a) at least part of the glutenin polymorphisms in wild emmer can be accounted for by environmental factors and (b) the endosperm of wild emmer contains many allelic variants of glutenin storage proteins that are not present in bread wheat and could be utilized in breeding varieties with improved bread making qualities. PMID- 24240348 TI - Formation of optimal composite populations. AB - The optimal breed composition of a composite population is derived from straightbred and average heterotic effects. It is demonstrated that there is a unique breed composition which maximizes a bioeconomic objective for a composite of m breeds. A forward stepwise approach for determination of the number of breeds to include in the composite population is advocated. Two examples of optimal composite populations are presented and briefly discussed using simulated net returns to weaning and through slaughter as objectives. PMID- 24240349 TI - In vitro selection of barley and wheat for resistance against Helminthosporium sativum. AB - Calli derived from immature embryos of barley and wheat genotypes were screened for their resistance to purified culture filtrate produced by the fungus Helminthosporium sativum P.K. and B. Two selection methods were used: a continuous method in which four cycles of selection were performed one after another on toxic medium and a discontinuous method in which a pause on non-toxic medium was given after the second or third cycle of selection. The latter was superior as it allowed the calli to regain their regeneration ability. About 3,000 calli from two barley genotypes and 2,000 from two wheat genotypes were used for selection. The selection with the pathotoxins resulted in 6% to 17% surviving calli. Toxin tolerant callus lines of barley were characterised by protein isozymes. Zymograms showed one more isozyme than with the unselected sensitive callus. Barley and wheat plants have been regenerated from callus lines surviving the toxin treatment and in vivo testing against pathogen revealed that the majority of these plants were less sensitive. PMID- 24240350 TI - DNA synthesis and cytoplasmic differentiation in tapetal cells of normal and cytoplasmically male sterile lines of Petunia hybrida. AB - A new method is described by which tapetal cells may be isolated from anthers of cytoplasmic male sterile (CMS) and fertile lines of Petunia hybrida. Using a combination of stereometry and Feulgen densitometry it has been possible to chart DNA synthesis and nuclear division with great precision within these cells. Results are presented which show CMS lines both to synthesize far less DNA than the fertiles and also to undergo less cell division. These differences in DNA kinetics and cytokinesis are obvious long before any differences between sterile and fertile lines may be detected in the meiocyte mass. In addition to these difference in nuclear behaviour, the tapetal cells of CMS lines also synthesize far lower levels of rough endoplasmic reticulum than do their fertile counterparts. Again, this difference is evident at a very early stage of anther development when all other cell components, including mitochondria and plastids, appear normal. These data are discussed in terms of the very special differentiation undergone by tapetal cells in angiosperms, and the conclusions drawn are considered in the perspective of current hypotheses proposed to explain the operation of CMS. PMID- 24240351 TI - The effect of caffeine on tear secretion. AB - PURPOSE: Caffeine, probably the most widely consumed psychoactive substance, is claimed to have conflicting effects on some tear film dynamics. This study sought to investigate the effect of orally ingested caffeine on tear secretion. METHODS: In an examiner-masked, placebo-controlled, crossover experimental model, the effect of caffeine intake on tear secretion was studied in 41 healthy volunteers aged 20 to 26 years (mean, 23.0 +/- 2.1 years). Participants were randomly assigned into two groups, A and B, to receive two different treatments in two sessions. Subjects in group A were exposed to 5.0 mg/kg body weight of caffeine dissolved in 200 mL of water on their first visit, whereas those in group B were exposed to 200 mL of water. On the second visit, however, the order of treatment was reversed. Schirmer 1 scores were measured repeatedly at 45, 90, 135, and 180 minutes after treatment. The baseline Schirmer 1 scores were compared with posttreatment scores. RESULTS: Schirmer 1 scores increased after caffeine intake. The increase was statistically significant at 45 and 90 minutes (p < 0.05) after caffeine intake. Age, body mass, and blood pressure had no correlation with Schirmer 1 scores (Spearman correlation test, p > 0.05). There was no influence of gender in caffeine's effect on tear secretion (F = 0.994, p = 0.399). CONCLUSIONS: From our study, orally ingested caffeine appears to stimulate tear secretion in healthy non-dry eye subjects. PMID- 24240352 TI - Intraocular lens power calculation: a challenging case. AB - PURPOSE: To highlight different methods in calculating intraocular lens (IOL) power in the case of undetectable keratometric (K) readings. CASE REPORT: A 54 year-old woman was referred to us for cataract surgery in her left eye. The slit lamp examination revealed the presence of corneal scars that did not allow us to take reliable K readings. To calculate them, the following regression formula was used: K= Rx-42.613/-0.0424*AL. The IOL power calculation was performed aiming at a postoperative error = -0.5 diopters. One month after surgery, the uncorrected visual acuity was 20/100 and the best spectacles corrected visual acuity was 20/25 with +1.0 -4 * 180 (-1.0 diopter spherical equivalent). CONCLUSIONS: This seems to be a reliable method to calculate the IOL power when K readings are undetectable, but to make a definitive statement, prospective studies are needed. PMID- 24240353 TI - Effect of antibiotic drops on adverse events during extended lens wear. AB - PURPOSE: Overnight lens wear is associated with increased lens contamination and risk of developing a corneal infiltrate or infectious event. Antibacterial lenses have been proposed as a potential strategy for reducing lens contamination. A proof-of-principle study was conducted to investigate what effect control of potential pathogens, through the use of antibiotic eye drops, would have on the incidence of corneal infiltrative events (CIEs) and on the ocular microbiota and lens contamination. METHODS: This is a prospective, open-label, controlled, parallel-group, 1-month clinical study in which 241 subjects were dispensed with lotrafilcon A silicone hydrogel lenses for 30 days of continuous wear. Subjects were randomized into either test (moxifloxacin 0.5%) or control (rewetting solution) group. One drop was instilled into each eye on waking and before sleeping, while lenses were on-eye. Follow-ups were conducted after one night and 1 month. Lid margin swabs were taken at baseline and at 1 month and worn lenses were aseptically collected at 1 month. RESULTS: The incidence of CIEs was not significantly different between the test (2.6%) and control (3.9%) groups (p = 0.72). Microorganism levels from the test group swabs were significantly lower than those from the control group (p = 0.001). Gram-positive bacteria were less frequently recovered from lower lid swabs from the test group (39.6% vs. 66.0% [p < 0.001], test vs. control, respectively) or from contact lens samples (1.9% vs. 10.5% [p = 0.015], test vs. control, respectively), but there was no difference in gram-negative bacteria (GNB). Corneal infiltrative events were associated with higher levels of lens contamination (p = 0.014) and contamination of lenses with GNB (CIE: 7.3% vs. 0.6% [p = 0.029], GNB contamination vs. no GNB contamination, respectively). DISCUSSION: Twice-daily antibiotic instillation during continuous wear of lenses did not significantly influence the rate of inflammatory events. Corneal infiltrative events were associated with higher levels of lens contamination in general and with contamination by GNB specifically. PMID- 24240354 TI - Corneal inflammatory events with daily silicone hydrogel lens wear. AB - PURPOSE: This study aimed to determine the probability and risk factors for developing a corneal inflammatory event (CIE) during daily wear of lotrafilcon A silicone hydrogel contact lenses. METHODS: Eligible participants (n = 218) were fit with lotrafilcon A lenses for daily wear and followed up for 12 months. Participants were randomized to either a polyhexamethylene biguanide-preserved multipurpose solution or a one-step peroxide disinfection system. The main exposures of interest were bacterial contamination of lenses, cases, lid margins, and ocular surface. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining free from a CIE, and multivariate Cox proportional hazards regression was used to model the hazard of experiencing a CIE. RESULTS: The KM unadjusted cumulative probability of remaining free from a CIE for both lens care groups combined was 92.3% (95% confidence interval [CI], 88.1 to 96.5%). There was one participant with microbial keratitis, five participants with asymptomatic infiltrates, and seven participants with contact lens peripheral ulcers, providing KM survival estimates of 92.8% (95% CI, 88.6 to 96.9%) and 98.1% (95% CI, 95.8 to 100.0%) for remaining free from noninfectious and symptomatic CIEs, respectively. The presence of substantial (>100 colony forming units) coagulase-negative staphylococci bioburden on lid margins was associated with about a five-fold increased risk for the development of a CIE (p = 0.04). CONCLUSIONS: The probability of experiencing a CIE during daily wear of lotrafilcon A contact lenses is low, and symptomatic CIEs are rare. Patient factors, such as high levels of bacterial bioburden on lid margins, contribute to the development of noninfectious CIEs during daily wear of silicone hydrogel lenses. PMID- 24240355 TI - Idiopathic sclerochoroidal calcification. AB - PURPOSE: Sclerochoroidal calcification is a rare ocular condition characterized by multifocal, yellow-white elevated fundus lesions typically located in the superotemporal quadrant along the superior arcades. The pathology of calcification can be classified as dystrophic, metastatic, or idiopathic. Vision threatening complications may arise, such as choroidal neovascular membrane and serous retinal detachment. The pathogenesis of sclerochoroidal calcification remains unclear. CASE REPORT: A 72-year-old Caucasian male patient presented to the clinic for routine examination. Fundus evaluation revealed bilateral, multifocal, pale yellow elevated lesions in the superotemporal fundus. Ultrasonography showed a focal area of hyper-reflectivity located in the posterior retina of both eyes, and optical coherence tomography showed an intact retina overlying the elevated lesions in the choroid. Systemic evaluation for dystrophic and metastatic calcification was negative, and the patient was diagnosed with idiopathic sclerochoroidal calcification. CONCLUSIONS: It is important to distinguish sclerochoroidal calcification from other conditions to prevent unnecessary intervention. Calcification of body tissues warrants a systemic evaluation, including screening for calcium and phosphorous levels, to rule out underlying systemic disease. If a biochemical abnormality is discovered, it can be appropriately treated with supplements. If calcification is deemed idiopathic, then annual dilated examinations are recommended to monitor the fundus lesions. Visual prognosis for sclerochoroidal classification is good, as the lesions are typically located away from the macula and foveal encroachment is rare. PMID- 24240356 TI - Updating the evidence on patent foramen ovale closure versus medical therapy in patients with cryptogenic stroke: a systematic review and comprehensive meta analysis of 2,303 patients from three randomised trials and 2,231 patients from 11 observational studies. AB - AIMS: We aimed at updating the evidence coming from randomised and observational studies of patent foramen ovale (PFO) closure compared to medical therapy in patients with cryptogenic stroke (CS). METHODS AND RESULTS: Comparative studies of PFO closure versus medical therapy published or presented through March 2013 were identified. Data from 2,303 patients in three randomised clinical trials (RCTs) and from 2,231 patients in 11 observational studies were included. In RCTs, the stroke hazard ratio (HR) for PFO closure versus medical therapy was 0.62 (95% confidence interval [CI]: 0.34-1.11; p=0.10 in the random effects model) with no significant heterogeneity or systematic bias. There was no significant difference in transient ischaemic attacks (TIA) (HR 0.77, 95% CI: 0.46-1.32; p=0.34) and no study-related deaths occurred. Pooling trials of the AMPLATZER PFO occluder device resulted in a significant reduction of stroke (HR 0.44, 95% CI: 0.20-0.95; p=0.04). Procedural success, new onset atrial fibrillation and cardiac thrombus were observed more frequently with the STARFlex compared with the AMPLATZER device. In observational studies, with high potential for baseline confounders, PFO closure was found to reduce the risk of recurrent stroke significantly (HR 0.23, 95% CI: 0.11-0.49; p<0.01 in the random effects model), with no significant effect on TIAs. CONCLUSIONS: In RCTs, unlike observational studies, PFO closure compared with medical therapy failed to achieve a statistically significant reduction in recurrent stroke. However, pooling RCTs of the AMPLATZER PFO occluder device yielded a statistically significant reduction in stroke over medical treatment that may warrant further investigation. PMID- 24240357 TI - Immunogold localization of nodule-specific uricase in developing soybean root nodules. AB - Immunogold labeling was used to study the time of appearance and distribution of a nodule-specific form of uricase (EC 1.7.3.3) in developing nodules of soybean (Glycine max (L.) Merr.) inoculated with Bradyrhizobium japonicum. The enzyme was detected in thin sections of tissue embedded in either L R White acrylic resin or Spurr's epoxy resin, by employing a polyclonal antibody preparation active against a subunit of soybean nodule uricase. Antigenicity was better preserved in L R White resin, but ultrastructure was better maintained in Spurr's. Uricase was first detectable with protein A-gold in young, developing peroxisomes in uninfected cells, coincident with the release of Bradyrhizobium bacteroids from infection threads in adjacent infected cells. As the peroxisomes enlarged, labeling of the dense peroxisomal matrix increased. Gold particles were never observed over the paracrystalline inclusions of peroxisomes, however. Despite a close association between enlarging peroxisomes and tubular endoplasmic reticulum, uricase was not detectable in the latter. In mature nodules, labeling of uricase was limited to the large peroxisomes in uninfected cells. Small peroxisome-like bodies present in infected cells did not become labeled. PMID- 24240358 TI - Re-formation of microtubules in Closterium ehrenbergii Meneghini after cold induced depolymerization. AB - Immunofluorescence microscopy was used to examine the re-formation of microtubules (MT), after cold-induced depolymerization, in Closterium ehrenbergii. The C. ehrenbergii cells undergo cell division followed by semicell expansion in the dark period of daily light-dark cycles. Five types of MTs, namely the MT ring, hair-like MTs around the nuclei, spindle MTs, radially arranged MTs and transverse wall MTs, appeared and disappeared sequentially during and following cell division. The wall MTs were distributed transversely only in the expanding new semicells. When cells were chilled in ice water, wall MTs in expanding cells were fragmented, and then disappeared as did the other types of MTs, within 5 min. When cells were warmed at 20 degrees C after 2 h chilling, wall MTs and the other types of MTs re-formed. At the early stage of wall-MT re-formation in expanding cells, small, star-like MTs were formed, and then randomly oriented MTs developed in both the expanding new and the old semicells. The MT ring was also re-formed at the boundary between the new and old semicells. There were no obvious MT-organizing centers in the random arrangement. As time passed, the randomly oriented wall MTs in the old semicells disappeared and those in the expanding new semicells gradually assumed a transverse orientation. These results indicate that wall MTs can be rearranged transversely after they have been re-formed and that nucleation of wall MTs is separable from the mechanism for ordering them. PMID- 24240359 TI - alpha-1,4-Glucan phosphorylase forms from leaves of spinach (Spinacia oleracea L.) I. In situ localization by indirect immunofluorescence. AB - Antisera were raised against two forms of alpha-1,4-glucan phosphorylase (EC 2.4.1.1) which had been purified from leaves of Spinacia oleracea L. Immunoglobulin G preparations were isolated from the antisera, and their specificity was ensured by immunoplobulin G preparations were used for in situ localization of the two phosphorylase forms in spinach leaf thin sections by indirect immuno-fluorescence. Both enzyme forms were present in the palisade and spongy parenchyma and in the guard cells, but their intracellular distribution was complementary. One phosphorylase form (designated as the chloroplastic form) was restricted to the stromal space of chloroplasts whereas the other (the non chloroplastic form) was present only in the cytoplasm of chloroplast-containing cells. Thus, the phosphorylases represent two distinct compartment-specific enzyme forms which reside within the same photosynthetically active mesophyll cell. PMID- 24240360 TI - Monoclonal antibodies to plant plasma-membrane antigens. AB - Murine monoclonal antibodies to membrane antigens were generated by immunization with a crude cellular membrane preparation from suspension-cultured cells of Nicotiana glutinosa L. From a panel of thirteen monoclonal antibodies, seven were found to be directed against antigens present on the plasma-membrane by immunofluorescence visualization of antibody binding to the surface of isolated protoplasts. The corresponding set of plasma-membrane antigen(s) were present in root, shoot and leaf tissue and some but not all of these antigens were of wide species distribution, being found in Nicotiana tabacum L., N. plumbaginifolia L., Glycine max L., Phaseolus vulgaris L. and Triticum aestivum L. Topologically specific labeling of intact protoplasts with a monoclonal antibody reactive with an epitope present on the plasma-membrane specifically labeled a membrane fraction which equilibrated at a density of 1.14 kg/l following centrifugation in a sucrose gradient. In addition to use as biochemical markers for fractionation and molecular characterization of plasma-membranes, these monoclonal antibodies provide the basis for new selection tools in plant cell and gene manipulations. PMID- 24240361 TI - Aberrant microtubule organization can result in genetic abnormalities in protoplast cultures of Vicia hajastana Grossh. AB - Protoplast cultures of Vicia hajastana have a high division frequency. However, 20-40% of the microcolonies fail to develop beyond the 20-30-cell stage. Aneuploids and polyploids were found in early divisions and persisted in older cultures. The resulting protoplast-derived suspension culture differed karyologically from the original culture. Karyokinesis and cytokinesis were studied using simultaneous staining of microtubules (MT) by immunofluorescence, DNA by Hoechst 33258 (2-[2-(4-hydroxyphenyl)-6-benzimidazoyl]-6-[1-methyl-4 piperazyl]benzimidazole) and cell walls by Calcofluor. Freshly prepared protoplasts showed mitoses and high frequencies of binucleate cells, which probably resulted mainly from failure of cytokinesis. In early divisions, many mitoses showed metaphase chromosomes with kinetochore MT but lacking polar MT. These aberrant mitoses probably accounted for an increase in hyperploid cells observed in protoplast cultures. Multipolar spindles, which gave rise to hypoploid cells, were also seen in the early divisions. Telophase abnormalities included dislocated phragmoplasts and incomplete formation of cross walls. Many divisions resulted in daughter nuclei of unequal size. Unequal segregation of chromosomes was detected by cytofluorimetric measurements of telophase nuclei stained with Hoechst. After 5 d of culture, 91% of the divisions with incomplete cross walls also contained different-size nuclei; conversely, 78% of the divisions with fully formed cross walls contained nuclei of equal size. The malfunctioning of spindles and phragmoplasts in the same cells indicates a functional interdependence of the different MT configurations in mitosis. During the first 24 h of culture, a high frequency of abnormalities was found in spindles, cross-wall formation and chromosome segregation; this was reduced substantially in the cells undergoing first division by 48 h. The data indicate that it may be possible to manipulate the frequency of abnormalities by controlling the onset of the first division in protoplast cultures. PMID- 24240362 TI - Prophase bands of microtubules occur in protoplast cultures of Vicia hajastana Grossh. AB - Circumnuclear bands of microtubules (MT) have been found in the prophase of mitoses in cultured protoplasts of Vicia hajastana. The timing of the appearance and disappearance of the prophase band of MT (PB) relative to the stage of mitosis was studied using simultaneous staining of MT by immunofluorescence and DNA by Hoechst 33258. These protoplasts regenerate into unorganized tissue. Pre prophase bands of MT have previously been found only in highly organized tissues of higher plants. The role of PB in cell division is discussed. PMID- 24240363 TI - Plant regeneration from callus cultures of several soybean genotypes via embryogenesis and organogenesis. AB - Using callus derived from immature embryos, regeneration of viable plants was obtained in soybean (Glycine max (L.) Merr.). Depending on the composition of the medium, regeneration occurred via embryogenesis or via organogenesis. Embryogenesis resulted when embryos were plated on Murashige and Skoog (MS) medium containing 43 MUM alpha-naphthaleneacetic acid. In work with the cultivar Williams 82, the addition of 5.0 MUM thiamine HCl increased embryogenesis from 33% to 58% of the embryos plated. Addition of 30 MUM nicotinic acid to the MS medium enhanced embryogenesis further to 76%. Organogenesis was obtained when medium containing 13.3 MUM 6-benzylaminopurine, 0.2 MUM and alpha naphthaleneacetic acid and four times the normal concentration of MS minor salts was used. Histological studies of these cultures confirmed the organogenic and embryogenic nature of the cultures, by demonstrating the formation of shoot buds and somatic embryos, respectively. Similar responses were obtained in all 54 genotypes tested in this manner. The cultures retained the ability to regenerate complete plants for at least 12 months and 12-15 subcultures. Seeds have been obtained from several regenerated plants and when grown in the field these produced normal-appearing fertile plants. PMID- 24240364 TI - Proteolysis in Euglena gracilis : II. Soluble and particle-bound acidic proteinase activities of the cysteine and aspartic types during growth and chloroplast development. AB - Endoproteolytic activities (EC 3.4.22. and 23.) of cell-free extracts of Euglena gracilis, measured by autolysis and azocaseinolysis, vary considerably during the culture growth cycle. They are high in the lag phase, drop sharply up to the mid logarithmic phase, and then rise again reaching the initial high levels in the stationary phase. This pattern has been observed for both the soluble and the particulate proteolytic activities of four cell types differing with regard to the developmental state of the chloroplast: dark-grown, light-induced, and light grown wild-type cells, as well as light-grown apoplastic W3BUL mutant cells, all on a glucose-based medium. Therefore, the activity of the main intracellular proteinases is neither directly nor indirectly light-regulated, but seems to be controlled by the availability of nutrients. Endogenous inhibitors of proteinases could not be detected. Cysteine proteinase activity has been found in the soluble and the particulate fractions, but aspartic proteinase activity in the latter ones only. Different cysteine proteinases may be present in the two fractions, during the different growth phases, and in the four cell types studied. PMID- 24240365 TI - Microbody transition in greening watermelon cotyledons Double immunocytochemical labeling of isocitrate lyase and hydroxypyruvate reductase. AB - Microbody transition during the greening of watermelon cotyledons (Citrullus vulgaris Schrad.) was studied by double immunocytochemical labeling of the glyoxysomal marker enzyme isocitrate lyase and the peroxisomal marker enzyme hydroxypyruvate reductase. In order to analyze the immunocytochemistry, developmental stages representing the glyoxysomal, microbodytransition and peroxisomal stages were chosen, taking into account the time course of enzyme activity and the amounts of the respective antigens. It was shown that during microbody transition, between 83 and 91% of all the tested microbodies contained isocitrate lyase as well as hydroxypyruvate reductase, which was significantly higher than in the glyoxysomal and peroxisomal stages of development. Comprehensive controls precluded labeling artifacts. Our results support the one population hypothesis first proposed by Trelease et al. (1971, Plant Physiol. 48, 461-465). PMID- 24240366 TI - Patterns of protein synthesis during the germination of pea axes, and the effects of an interrupting desiccation period. AB - As germination of axes of Pisum sativum L. seeds progressed, profound quantitative and qualitative changes occurred in the patterns of protein synthesis. This was shown by fluorography of gels following two-dimensional polyacrylamide gel electrophoresis separation of [(35)S]methioninelabelled proteins. The effects of desiccation during germination on these in-vivo protein synthesis patterns were followed. Desiccation differentially affected the synthesis of proteins. Usually, however, upon rehydration following desiccation the types of proteins being synthesized were recognizable as those synthesized earlier during imbibition of control, once-imbibed axes: seeds imbibed for 8 h, and then dried, did not recommence synthesis of proteins typical of 8-h-imbibed control seeds, but rather of 4-h-imbibed control seeds. Seeds imbibed for 12 h, and then dried and rehydrated, synthesized proteins typical of 4-h-and 8-h control seeds. Thus drying of germinating pea axes caused the proteinsynthesizing mechanism to revert to producing proteins typical of earlier stages of imbibition. Drying during germination never caused the seed to revert to the metabolic status of the initial mature dry state, however. PMID- 24240367 TI - Translational regulation of protein synthesis during light-induced chloroplast development in Euglena. AB - Control of gene expression in Euglena was examined during light-induced chloroplast development. Greening was achieved under standard conditions which allowed the synthesis of all plastid proteins in both cytoplasmic and chloroplastic compartments, or under experimentally modified conditions inducing the preferential synthesis of the photosystem II (PSII) light-harvesting antenna or reaction centers. The relative composition of total mRNAs in cellular, cytoplasmic or chloroplastic fractions, as analyzed by their in-vitro translation products in cell-free systems did not significantly change during the in-vivo protein-synthesis processes which are specific to each greening system. By contrast, cytoplasmic polysomal mRNAs extracted during the selective recovery phase of PSII light-harvesting antennae provided a major in-vitro synthesis product of 28 kDa which could correspond to a precursor of the main 26-kDa apoprotein of the light-harvesting chlorophyll a/b protein complex. Similarly, the in-vivo selective synthesis of the 41-kDa and 51-kDa polypeptides of PSII reaction centers was concomitant with an enrichment of plastid polysomes in mRNA species coding for polypeptides of the same molecular weight. These observations confirm that protein synthesis during chloroplast development in Euglena is weakly regulated at the transcription level and they demonstrate that translational regulation occurs in both the cytoplasmic and the chloroplastic compartments. PMID- 24240368 TI - Purification and properties of ascorbate free-radical reductase from potato tubers. AB - Ascrobate free-radical reductase (EC 1.6.5.4) from potato tubers was purified to apparent homogencity by a method which included ammonium-sulfate precipitation, gel filtration and chromatography on diethylaminoethyl cellulose and hydroxylapatite. Gel filtration and gel electrophoresis showed that the purified enzyme was monomeric with a molecular weight of about 42 000. Enzyme activity was heat lable and severely inhibited by thiol reagents. The Km values for enzyme substrates were estimated. PMID- 24240369 TI - Effect of auxin and abscisic acid on cell wall extensibility in maize coleoptiles. AB - Plastic and elastic in-vitro extensibilities (E pland E el ) of cell walls from growing maize (Zea mays L.) coleoptile segments were measured by stretching frozen-thawed tissue, pre-extended to its in-vivo length, at constant force (creep test) in a custom-buildt extensiometer, equipped with a linear displacement transducer. The indole-3-acetic acid (IAA)-induced change of E pl (DeltaE pl ) is strictly correlated with the growth rate for a period of 3-4 h. Subsequently, DeltaE plremains constant while the growth rate is slowing down. Since this discrepancy can be accounted for by a growth-dependent reduction of osmotic pressure, it is concluded that DeltaE plrepresents quantitatively the relative increase of in-vivo extensibility (cell wall loosening) involved in IAA mediated cell growth over a much longer time. On the other side it is argued that the growth rate may not be strictly correlated with wall extensibility during long-term growth. Abscisic acid (ABA) inhibits segment growth induced by auxin, fusicoccin, or exogenous acid, and this effect can be quantitatively attributed to an ABA-mediated reduction of cell wall extensibility as determined by the DeltaE plmeasurement. Both, IAA and ABA have no effect on total protein synthesis, RNA synthesis, and amount of osmotic solutes. Fusicoccin-induced proton excretion is only slightly inhibited by ABA. In contrast to ABA, growth inhibition by cycloheximide (CHI) is always much larger than the concomitant reduction of DeltaE pl , indicating that a further growth parameter is also involved in the inhibition of cell growth by CHI. DeltaE el is not affected by either IAA, ABA, or CHI. It is concluded that deltaE pl as determined by the applied method, represents a relative measure of the actual in-vivo extensibility of the growing cell wall at the very moment when the tissue is killed, rather than an average extensibility accumulated over some immediate-past period of time as suggested by Cleland (1984, Planta 160, 514-520). Hence, we further draw the conclusion that IAA and ABA control of cell growth can entirely be attributed to a modulation of cell wall extensibility by these hormones in maize coleoptiles. PMID- 24240370 TI - The role of beta-dimethylsulphoniopropionate, glycine betaine and homarine in the osmoacclimation of Platymonas subcordiformis. AB - The tertiary sulphonium compound, beta-dimethylsulphoniopropionate (DMSP) and the quaternary ammonium compounds glycine betaine and homarine are important osmotica in Platymonas subcordiformis cells. Following hypersaline stresses the compounds were accumulated after a lag period of 3 h and equilibrium concentrations were reached 6 h later. In contrast to these organic solutes, mannitol was synthesised immediately and equilibrium concentrations were reached within 90 min. Hyposaline stresses induced losses of the organic solutes from the cells. The ions K(+), Na(+), Cl(-) and the above organic solutes can account for the osmotic balance of the cells. PMID- 24240371 TI - Evidence for a functional membrane barrier in the transition zone between the flagellum and cell body of Chlamydomonas eugametos gametes. AB - Evidence is presented which supports the concept of a functional membrane barrier in the transition zone at the base of each flagellum of Chlamydomonas eugametos gametes. This makes it unlikely that agglutination factors present on the surface of the cell body can diffuse or be transported to the flagellar membrane. The evidence is as follows: 1) The glycoprotein composition of the flagellar membrane is very different to that of the cell-body plasma membrane. 2) The flagella of gametes treated with cycloheximide, tunicamycin or alpha, alpha'-dipyridyl become non-agglutinable but the source of agglutination factors on the cell body is not affected. 3) Even under natural conditions when the flagella are non agglutinable, for example in vis-a-vis pairs or in appropriate cell strains that are non-agglutinable in the dark, the cell bodies maintain the normal complement of active agglutinins. 4) When flagella of living cells are labeled with antibodies bound to fluorescein, the label does not diffuse onto the cell-body surface. 5) When gametes fuse to form vis-a-vis pairs, the original mating-type specific antigenicity of each cell body is slowly lost (probably due to the antigens diffusing over both cell bodies), while the specific antigenicity of the flagellar surface is maintained. Even when the flagella of vis-a-vis pairs are regenerated from cell bodies with mixed antigenicity, the antigenicity of the flagella remains matingtype-specific. 6) Evidence is presented for the existence of a pool of agglutination factors within the cell bodies but not on the outer surface of the cells. PMID- 24240372 TI - Stomatal aperture, photosythesis and water fluxes in mesophyll cells as affected by the abscission of leaves. Simultaneous measurements of gas exchange, light scattering and chlorphyll fluorescence. AB - Carbon dioxide exchange, transpiration, chlorophyll fluorescence and light scattering of leaves of Lycopersicom esculentum, Helianthus annuus and Arbutus unedo were measured simultaneously before and after abscission of leaves. Scattering of a weak green measuring beam was used to monitor water fluxes across the thylakoid membranes of the mesophyll. When leaves were cut under water, stomata initially closed partially and then occasionally exhibited distinct regulatory oscillations. As stomata closed, light scattering decreased indicating water influx into the mesophyll. Stomatal oscillations were accompanied, with small but noticeable phase shifts, by oscillations of water fluxes at the thylakoid level. These fluxes could be distinguished from the water fluxes accompanying light-dependent ion pumping across the thylakoids by the concomitant chlorophyll fluorescence signals. The latter record energy-dependent ion fluxes in addition to redox changes of the electron-transport chain. As stomata closed partially after cutting a leaf under water, photosynthesis decreased. In Arbutus unedo and Helianthus annuus leaves, transient stomatal closure was insufficient to account for transient inhibition of photosynthesis which appeared to be brought about by transfer of an inhibitory solute through the petiole into the mesophyll. This solute also stimulated respiration in the dark. When leaves were cut in air, stomata opened transiently (Iwanoff effect) before wilting enforced closure. Photosynthesis followed the stomatal responses, increasing during opening and decreasing during closure. PMID- 24240373 TI - Effects of abscisic acid on sequestration and exchange of Na(+) by barley roots. AB - Excised Na(+)-starved barley roots were suspended in solutions of Na(+) in combination with NO 3 (-) , Cl(-), and SO 4 (2-) , and effects of the added phytohormone, abscisic acid (ABA), to the medium were determined. Abscisic acid increased the rate of Na(+) ((22)Na(+)) accumulation and the amount of Na(+) deposited in the vacuoles. These stimulating effects of ABA were modified by anions following the sequence NO 3 (-) >Cl(-)>SO 4 (2-) . Testing whether the magnitude of the pH gradient across the plasmalemma of the cells of the root cortex affects rates of Na(+) accumulation and their dependence upon ABA, we observed that, in the pH range from 4 to 8, the ABA-induced stimulation was strongest at pH 5.8, and least at pH 4. Changes in pH during the experiment caused changes in the rates of Na(+) accumulation in agreement with experiments performed at constant pH values. Simultaneously with ABA-enhanced accumulation, loss of Na(+) occurred. Loss of Na(+) was strongest at pH 4 and was affected by anions, being greatest with SO 4 (2-) and following the sequence SO 4 (2-) >Cl( )>NO 3 (-) . On the basis of the finding that initial acceleration of uptake as well as loss of Na(+) depended on the pH of the medium we suggest that, in barley roots, ABA stimulates an exchange of Na(+) for H(+) at the plasmalemma of the cortical cells. The results indicate that ABA-stimulated expulsion of Na(+), in combination with ABA-stimulated sequestration in the vacuoles, constitutes one of the mechanisms which enable barley plants to tolerate higher than normal levels of Na(+). PMID- 24240374 TI - Isocitrate lyase of the alga Chlorogonium elongatum: Immunological quantification in relation to growth conditions. AB - Isocitrate lyase (EC 4.1.3.1) from the acetate flagellate Chlorogonium elongatum was studied in relation to growth conditions. In cells growing heterotrophically or photoheterotrophically with acetate (2 g . l(-1)) specific activities of 0.453 and 0.335 MUmol glyoxylate . min(-1) . mg(-1) protein, respectively, were found in the cell-free extracts. The malate synthase activity of heterotrophically grown Chlorogonium cells was found to be 0.572 nmol . min(-1) . mg(-1) protein. In the presence of inhibitors acting on transcription and translation there was no increase in isocitrate lyase activity; this would indicate that the enzyme was synthesized de novo in response to changing conditions in the surroundings. Using an enzyme immunoassay it was shown that the activity and amount of enzyme rose concomitantly when the cells were supplied with acetate, irrespective of whether they had been cultivated photoheterotrophically or heterotrophically on acetate. PMID- 24240375 TI - Light and metabolite regulation of the synthesis of ribulose-1,5-bisphosphate carboxylase/oxygenase and the corresponding mRNAs in the unicellular alga Chlorogonium. AB - In the unicellular green alga Chlorogonium elongatum, the synthesis of the plastid enzyme ribulose bisphosphate carboxylase/oxygenase (RuBPCase) and its mRNAs is under the control of light and acetate. Acetate is the sole metabolizable organic carbon source for this organism. Light greatly promotes the synthesis of RuBPCase and the increase in the concentration of the mRNAs of both subunits of the enzyme while acetate has a strong inhibitory effect on this process. There is a good agreement between RuBPCase synthesis and the amount of translateable RuBPCase mRNA present in cells which are cultured under different conditions (autotrophic, heterotrophic, mixotrophic). During the transition period after transfer of the cells from heterotrophic to autotrophic growth conditions the amounts of the large and small subunits of the enzyme increase well coordinated. In contrast to the protein subunits the two subunit-mRNAs accumulate with different kinetics. PMID- 24240376 TI - The effects of light quality and intensity on the synthesis of ribulose-1,5 bisphosphate carboxylase and its mRNAs in the green alga Chlorogonium elongatum. AB - In the green alga Chlorogonium elongatum the promoting effect of light on the synthesis of ribulose bisphosphate carboxylase/oxygenase (RuBPCase) is mainly caused by blue light of wavelengths between 430 nm and 510 nm, with a maximum effect at about 460 nm. Blue light also causes an increase in the amounts of the mRNAs for the large and the small subunits of the enzyme. Furthermore, the concentration of RuBPCase is affected by the light energy fluence rate. The rate of synthesis as well as the maximal obtainable concentration of the enzyme are functions of the light energy fluence rate up to 26 W.m(-2). No further increase occurs beyond that intensity. The quantity of irradiation also alters the concentrations of the subunit mRNAs. The results indicate that the changes in the mRNA levels are the major regulatory steps in the light-dependent synthesis of the RuBPCase enzyme. PMID- 24240377 TI - Purification and properties of an endospermic protein of maize associated with the Opaque-2 and Opaque-6 genes. AB - Maize endosperms accumulate during development a large amount of storage proteins (zeins). The rate of zein accumulation is under the control of several regulatory genes. Two of these, the opaque-2 and opaque-6 mutants, lower the zein level, thus improving the nutritional quality of maize meals. An endosperm protein of Mr 32 000 (b-32) appears to be correlated with the zein level. The b-32 protein is encoded by the opaque-6 gene which, in turn, is activated by opaque-2. We report the purification, amino-acid composition and peptide map of b-32 protein. Furthermore we demonstrate that the protein exists as a monomer likely located in the soluble cytoplasm. As a step towards the isolation of a complementary-DNA clone for b-32 protein, the purification of its corresponding mRNA is described. PMID- 24240378 TI - Protein inhibitors of microbial proteinases from wheat, rye and triticale. AB - Specific protein inhibitors of microbial serine proteinases were isolated from wheat (Triticum aestivum L.), rye (Secale cereale L.) and triticale using affinity chromatography on subtilisin-Sepharose 4B. The wheat inhibitor had an isoelectric point (pI) at pH 7.2, while the rye inhibitor consisted of two forms with pI values of 6.8 and 7.1. In triticale, two components were present with pIs 7.2 and 6.8. All the inhibitors had M r values of approx. 20 000. The isolated proteins were effective inhibitors of subtilisins Carlsberg and BPN', and of fungal proteinases (EC 3.4.21.14) from the genus Aspergillus, but they were completely inactive against trypsin (EC 3.4.21.4) chymotrypsin (EC 3.4.21.1) and pancreatic elastase (EC 3.4.21.36). The inhibitors formed complexes with subtilisin in a molar ratio of 1:1. The results of chemical modifications seem to indicate that the isolated inhibitors have methionine residues in their reactive sites. PMID- 24240379 TI - Cardiomyopathies and myocardial disorders in Africa: present status and the way forward. PMID- 24240380 TI - Article visibility: journal impact factor and availability of full text in PubMed Central and open access. PMID- 24240381 TI - Analysis of the omega-3 fatty acid content of South African fish oil supplements: a follow-up study. AB - INTRODUCTION: Globally the omega-3 (n-3) fatty acid supplement industry is expanding rapidly while consumers are becoming more aware of the health benefits of n-3 fatty acids. Our group conducted a survey in 2009 on 45 commercially available fish oil supplements on the South African market. The aim of the study was to determine the fatty acid composition and content of supplements for comparison with the claimed contents on the product label. The survey was repeated in 2012 on 63 supplements. METHODS: Sixty-three commercially available n 3 fatty acid supplements were analysed using gas-liquid chromatography to determine their fatty acid composition and content. RESULTS: This analysis has shown an improvement in the accuracy of EPA content (44% in 2009) declared on supplement labels compared to the 2012 (52%) survey. It was also evident that a higher percentage of supplements (13% in 2009 vs 35% in 2012) contained DHA levels higher than declared. In 2009, 64% of supplements cost R2.01 to R5.00 or more to achieve a daily intake of 500 mg EPA + DHA, compared to 81% in 2012. Forty-four per cent of supplements were found to be in the early stages of rancidity [conjugated diene (CD) levels] compared to 73% in 2009. More than 80% of supplements had peroxide levels higher than the recommended content as specified by the Global Organisation for EPA and DHA Omega-3 (GOED). The majority (81%; n = 51) of the supplements under study in 2012 had a 1.1-1.5:1 EPA-to-DHA ratio or less, compared to 56% in 2009. Almost a third (32%) of the supplements in the 2012 survey contained ethyl esters (EE) or a combination of ethyl esters and triglycerides. CONCLUSION: Although the results of the 2012 versus the 2009 analysis were encouraging in terms of the accuracy of EPA declared on the supplement labels, the high peroxide levels found in the supplement oils are of concern. High peroxide levels are associated with potential health implications. EE were present in some of the supplements, even though the safety of EE has not been confirmed in vulnerable groups such as pregnant women and children. PMID- 24240382 TI - Tumescentless endovenous radiofrequency ablation with local hypothermia and compression technique. AB - INTRODUCTION: Modern surgical management of chronic venous insufficiency is possible since the development of catheter-based minimally invasive techniques, including radiofrequency ablation (RFA) and the application of colour Doppler sonography. RFA technology requires the use of tumescent anaesthesia, which prolongs the operating time. Instilling tumescent anaesthesia percutaneously below the saphenous fascia is the steepest part of the learning curve. In our study, we compared operative and postoperative results of tumescentless RFA and RFA with tumescent anaesthesia, to investigate the necessity of tumescent anaesthesia. METHODS: A total of 344 patients with Doppler-confirmed great saphenous vein insufficiency underwent RFA between January and December 2012. Patients were divided into two groups according to anaesthetic management. Group 1 consisted of 172 patients: tumescent anaesthesia was given before the ablation procedure, and group 2 contained 172 patients: a local hypothermia and compression technique was used; no tumescent anaesthesia was administered. The visual analogue scale (VAS) was used and ecchymosis scores of the patients were recorded. Clinical examinations were performed at each visit and Doppler ultrasonography was performed in the first and sixth month. RESULTS: Mean ablation time was significantly lower in group 2 compared to group 1 (7.2 vs 18.9 min; p < 0.05). Skin burn and paresthesia did not occur. The immediate occlusion rate was 100% for both groups. No significant difference was found between the groups in terms of VAS and ecchymosis scores. All patients returned to normal activity within two days. The primary closure rate of group 1 was 98.2% and group 2 was 98.8% at six months, and there was no significant difference between the groups (p > 0.05). CONCLUSION: Eliminating tumescent infusion is a desirable goal. Tumescentless endovenous RFA with local hypothermia and compression technique appears to be safe and efficacious. Our technique shortens the operation time and prevents patient procedural discomfort. PMID- 24240383 TI - Clinical experience of repair of pectus excavatum and carinatum deformities. AB - OBJECTIVE: We present the results of surgical correction of pectus excavatum (PE) and pectus carinatum (PC) deformities in adults, and also report a new method of sternal support used in surgery for PE deformities. METHODS: We present the results of 77 patients between the ages of 10 and 29 years (mean 17) with PE (n = 46) or PC (n = 31) deformities undergoing corrective surgery from 2004 to 2011, using the Ravitch repair method. Symptoms of the patients included chest pain (15%) and tachycardia (8%). Three patients underwent repair of recurrent surgical conditions. RESULTS: All of the patients with dyspnoea with exercise experienced marked improvement at five months post operation. Complications included pneumothorax in 5.1% (n = 4), haemothorax in 2.6% (n = 2), chest discomfort in 57% (n = 44), pleural effusion in 2.6% (n = 2), and sternal hypertrophic scar in 27% (n = 21) of patients. Mean hospitalisation was eight days. Pain was mild and intravenous analgesics were used for a mean of four days. There were no deaths. Results after surgical correction were very good or excellent in 62 patients (80%) at a mean follow up of three years. Three patients had recurrent PE and were repaired with the Nuss procedure. In three patients who underwent the Ravitch procedure, a stainless steel bar was used for sternal support instead of Kirschner wire. CONCLUSION: Pectus deformities may be repaired with no mortality, low morbidity, very good cosmetic results and improvement in cardiological and respiratory symptoms. PMID- 24240384 TI - Alpha lipoic acid attenuates inflammatory response during extracorporeal circulation. AB - AIM: Extracorporeal circulation (ECC) of blood during cardiopulmonary surgery has been shown to stimulate various proinflammatory molecules such as cytokines and chemokines. The biochemical oxidation/reduction pathways of alpha-lipoic acid suggest that it may have antioxidant properties. METHODS: In this study we aimed to evaluate only patients with coronary heart disease and those planned for coronary artery bypass graft operation. Blood samples were obtained from the patients before the operation (P1) and one (P2), four (P3), 24 (P4) and 48 hours (P5) after administration of alpha-lipoic acid (LA). The patients were divided into two groups, control and LA treatment group. Levels of interleukin- 6 (IL-6) and -8 (IL-8), complement 3 (C3) and 4 (C4), anti-streptolysin (ASO), C-reactive protein (CRP) and haptoglobin were assessed in the blood samples. RESULTS: Cytokine IL-6 and IL-8 levels were significantly higher after surgery. Compared with the control groups, LA significantly decreased IL-6 and IL-8 levels in a time-dependent manner. CRP levels did not show significant variation in the first three time periods. CRP levels were higher after surgery, especially in the later periods. These results demonstrate that CRP formation depends on cytokine release. C3 and C4 levels were significantly higher after surgery than in the pre operative period. LA treatment decreased C3 and C4 levels. Therefore, LA administration may be useful for the treatment of diseases and processes where excessive cytokine release could cause oxidative damage. CONCLUSION: Our findings suggest a possible benefit of using LA during cardiac surgery to reduce cytokine levels. PMID- 24240386 TI - Novo Nordisk incretin and Cardiovascular Summit, Durban, June 2013. PMID- 24240385 TI - Prevalence of dyslipidaemia in statin-treated patients in South Africa: results of the DYSlipidaemia International Study (DYSIS). AB - INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and increased levels of low-density lipoprotein cholesterol (LDL-C) are an important modifiable risk factor. Statins lower LDL-C levels and have been shown to reduce CVD risk. Despite the widespread availability of statins, many patients do not reach the lipid targets recommended by guidelines. We evaluated lipid goal attainment in statin-treated patients in South Africa and analysed variables contributing to poor goal attainment as part of the DYSlipidaemia International Study (DYSIS). METHODS: This cross-sectional, observational study enrolled 1 029 consecutive South African patients consulting officebased physicians. Patients were at least 45 years old, had to be treated with a stable dose of statins for at least three months and had been fasting for 12 hours. We evaluated lipid goal attainment and examined variables associated with residual dyslipidaemia [abnormal levels of LDL-C, highdensity lipoprotein cholesterol (HDL-C) and/or triglycerides (TG)]. RESULTS: We found that 50.3% of the patients overall did not achieve target LDL-C levels and 73.5% of patients were at very high cardiovascular risk. In addition, 33.7% had low levels of HDL C, while 45.3% had elevated TG levels despite statin therapy. Asian and mixed ancestry patients but not black (vs Caucasian thnicity), as well as obese individuals in South Africa were more likely to still have dyslipidaemia involving all three lipid fractions. CONCLUSIONS: We observed that many patients in South Africa experienced persistent dyslipidaemia despite statin treatment, supporting the concept that there is a need for more intensive statin therapy or the development of novel treatment strategies. Measures aimed at combating obesity and other lifestyle-related risk factors are also vital for effectively controlling dyslipidaemia and reducing the burden of CVD. PMID- 24240387 TI - Allele frequencies for 26 STR loci in a population of Tuscany (Central Italy). AB - Allele frequencies for 26 short tandem repeats (STRs) were obtained from a sample of 203 unrelated individuals living in the area of Florence, Prato and Pistoia (Tuscany, Central Italy). These 26 loci are in addition to the existing 13 U.S. core loci and can help provide assistance in complex kinship testing when, for example, the alleged father is not available for testing. The results were compared with U.S. Caucasian, African American and Hispanic populations. PMID- 24240388 TI - Modulation between bilateral legs and within unilateral muscle synergists of postural muscle activity changes with development and aging. AB - The effect of development and aging on common modulation between bilateral plantarflexors (i.e., the right and left soleus, and the right and left medial gastrocnemius) (bilateral comodulation) and within plantarflexors in one leg (i.e., the right soleus and the right medial gastrocnemius) (unilateral comodulation) was investigated during bipedal quiet standing by comparing electromyography-electromyography (EMG) coherence among three age groups: adult (23-35 years), child (6-8 years), and elderly (60-80 years). The results demonstrate that there was significant coherence between bilateral plantarflexors and within plantarflexors in one leg in the 0- to 4-Hz frequency region in all three age groups. Coherence in this frequency region was stronger in the elderly group than in the adult group, while no difference was found between the adult and child groups. Of particular interest was the finding of significant coherence in bilateral and unilateral EMG recordings in the 8- to 12-Hz frequency region in some subjects in the elderly group, whereas it was not observed in the adult and child groups. These results suggest that aging affects the organization of bilateral and unilateral postural muscle activities (i.e., bilateral and unilateral comodulation) in the plantarflexors during quiet standing. PMID- 24240389 TI - Gait performance is not influenced by working memory when walking at a self selected pace. AB - Gait performance exhibits patterns within the stride-to-stride variability that can be indexed using detrended fluctuation analysis (DFA). Previous work employing DFA has shown that gait patterns can be influenced by constraints, such as natural aging or disease, and they are informative regarding a person's functional ability. Many activities of daily living require concurrent performance in the cognitive and gait domains; specifically working memory is commonly engaged while walking, which is considered dual-tasking. It is unknown if taxing working memory while walking influences gait performance as assessed by DFA. This study used a dual-tasking paradigm to determine if performance decrements are observed in gait or working memory when performed concurrently. Healthy young participants (N = 16) performed a working memory task (automated operation span task) and a gait task (walking at a self-selected speed on a treadmill) in single- and dual-task conditions. A second dual-task condition (reading while walking) was included to control for visual attention, but also introduced a task that taxed working memory over the long term. All trials involving gait lasted at least 10 min. Performance in the working memory task was indexed using five dependent variables (absolute score, partial score, speed error, accuracy error, and math error), while gait performance was indexed by quantifying the mean, standard deviation, and DFA alpha of the stride interval time series. Two multivariate analyses of variance (one for gait and one for working memory) were used to examine performance in the single- and dual-task conditions. No differences were observed in any of the gait or working memory dependent variables as a function of task condition. The results suggest the locomotor system is adaptive enough to complete a working memory task without compromising gait performance when walking at a self-selected pace. PMID- 24240390 TI - Differences between Han Chinese and Caucasians in transcranial magnetic stimulation parameters. AB - The study was conducted to investigate the difference between Han Chinese and Caucasians on various parameters measured from responses to transcranial magnetic brain stimulation (TMS). Sixteen subjects were studied in each group. A circular coil at the vertex was used for stimulation, whilst recording surface electromyograms from right first dorsal interosseous. In the passive state, motor evoked potential (MEP) threshold, MEP recruitment, short-interval intracortical inhibition (SICI) and intracortical facilitation were measured. The MEP threshold, recruitment and silent period were also measured in the active state. Chinese subjects showed significantly higher passive thresholds (P < 0.005), less inhibition of the motor response (SICI, P < 0.0005) and a shorter silent period (P < 0.05). Differences in SICI appeared to be a consequence of the differences in passive threshold and were not seen when active threshold was used to determine the conditioning stimulus intensity. Differences in silent period may also reflect differences in cortical excitability rather than inhibitory processes, as they were not seen when the silent-period duration was expressed as a function of MEP size, rather than TMS intensity. There appears to be a significant difference in some TMS parameters between Han Chinese and Caucasian subjects. This may reflect an underlying difference in cortical excitability. PMID- 24240393 TI - Transgenic plants of Orchardgrass (Dactylis glomerata L.) from protoplasts. AB - We have demonstrated the transfer and expression of a foreign chimeric gene in the grass species, Dactylis glomerata L. This species is a member of the Gramineae sub-family Pooideae, which includes the small grain cereals, from which transformed plants have not yet been obtained. A chimeric hygromycin-resistance gene was introduced into protoplasts isolated from an embryogenic suspension culture, using heat shock followed by electroporation or polyethylene glycol treatment. Cell colonies resistant to 20 MUg/ml hygromycin were selected in liquid medium using an agarose bead type culture system. Transformed calli were identified by Southern hybridization. Embryogenic callus was induced to regenerate plants and transformed plants were shown to contain the hygromycin resistance gene. PMID- 24240392 TI - A direct vulnerable atherosclerotic plaque elasticity reconstruction method based on an original material-finite element formulation: theoretical framework. AB - The peak cap stress (PCS) amplitude is recognized as a biomechanical predictor of vulnerable plaque (VP) rupture. However, quantifying PCS in vivo remains a challenge since the stress depends on the plaque mechanical properties. In response, an iterative material finite element (FE) elasticity reconstruction method using strain measurements has been implemented for the solution of these inverse problems. Although this approach could resolve the mechanical characterization of VPs, it suffers from major limitations since (i) it is not adapted to characterize VPs exhibiting high material discontinuities between inclusions, and (ii) does not permit real time elasticity reconstruction for clinical use. The present theoretical study was therefore designed to develop a direct material-FE algorithm for elasticity reconstruction problems which accounts for material heterogeneities. We originally modified and adapted the extended FE method (Xfem), used mainly in crack analysis, to model material heterogeneities. This new algorithm was successfully applied to six coronary lesions of patients imaged in vivo with intravascular ultrasound. The results demonstrated that the mean relative absolute errors of the reconstructed Young's moduli obtained for the arterial wall, fibrosis, necrotic core, and calcified regions of the VPs decreased from 95.3 +/- 15.56%, 98.85 +/- 72.42%, 103.29 +/- 111.86% and 95.3 +/- 10.49%, respectively, to values smaller than 2.6 * 10(-8) +/ 5.7 * 10(-8)% (i.e. close to the exact solutions) when including modified-Xfem method into our direct elasticity reconstruction method. PMID- 24240394 TI - Characterization of soybean tissue culture cell lines resistant to methionine analogs. AB - Several hundred soybean [Glycine max (L.) Merr.] cell lines resistant to ethionine were isolated either with or without chemical mutagenesis. of these, 26 were found to contain 2 to 22 times higher than normal levels of uncombined methionine. These 26 cell lines also contained higher than normal levels of S adenosylmethionine and S-methylmethionine, but the levels of free lysine, threonine, cysteine, valine, tyrosine and phenylalanine were not elevated. Isoleucine levels were only slightly elevated. These results suggest that the regulation of methionine synthesis in vivo is more likely to be later in the pathway (after homoserine phosphate) than early in the pathway. PMID- 24240391 TI - Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. AB - Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification. PMID- 24240395 TI - Homoserine kinase and threonine synthase in methionine-overproducing soybean tissue cultures. AB - To gain understanding of the regulation of methionine level in plants, we assayed homoserine kinase and threonine synthase in extracts of wild type and several methionine-overproducing soybean [Glycine max (L.) Merr.] callus lines. The specific activity of homoserine kinase was depressed by 45-73%, and that of threonine synthase by 26-43% in the high methionine lines. Cysteine inhibited threonine synthase in wild type and variant lines. Threonine synthase in two variant lines showed significantly less inhibition by cysteine and in one line was inhibited by threonine. Depressed threonine synthase activity may increase the availability of homoserine phosphate to the competing methionine biosynthetic pathway. PMID- 24240396 TI - Transient gene expression in electroporated Picea glauca protoplasts. AB - The reporter gene for chloramphenicol acetyltransferase (CAT) was introduced into white spruce (Picea glauca (Moench) Voss.) protoplasts by electroporation. CAT transient gene expression was increased by increasing the concentration of pCaMVCN plasmid and was affected by the level of the applied voltage. Highest CAT activities were obtained after electroporation with a pulse of 350V.cm(-1) having an exponential decay constant of approximately 105ms. Linearized plasmid constructs gave much higher levels of CAT activity than circular plasmid. Attempts to use the Escherichia coli beta-glucuronidase gene (beta-GUS) as a marker gene revealed very high levels of beta-GUS-like activity in electroporated protoplasts. This activity was mainly due to a small molecule and may mask successful transformation since beta-GUS-like activity increased when plasmid DNA was present during electroporation. PMID- 24240397 TI - Callus formation from mesophyll protoplasts of Fagus sylvatica L. AB - Viable protoplasts of European beech (Fagus sylvatica L.) were isolated from sterilized young leaves of juvenile (3-5 years) and mature (40 years) trees. Isolation in a saline solution containing 0.5% (w/v) Pectinol and 2% (w/v) Cellulase R-10 yielded 3*10(7) protoplasts per gram fresh weight. Protoplast culture in modified Kao and Michayluk (1975) medium resulted in cell wall regeneration and sustained cell divisions with the formation of colonies and microcalli. PMID- 24240398 TI - Vital DNA staining of agarose-embedded protoplasts and cell suspensions of Nicotiana plumbaginifolia. AB - The DNA of agarose-embedded protoplasts of Nicotiana plumbaginifolia was stained with Hoechst 33342 by immersing microscope slides, coated with immobilized protoplasts, into Erlenmeyer flasks containing consecutively dye solution, pH correcting washing solutions and culture medium. After staining, protoplasts regenerated cell walls, started to divide and proliferated to calli. The culture system with immobilized protoplasts permits rapid change of culture media and accurate control of experimental conditions. The staining technique offers the opportunity for continuous observation of chromosomal behaviour and cell dynamics in individual plant cells.The same staining procedure was successfully applied to DNA of plant cells in suspension. Flow cytometric analysis revealed a retarding effect of the dye on the cell cycle, but within hours the cells recovered and showed their normal growth characteristics as compared to the controls. PMID- 24240399 TI - The reductive transformation of decanones with immobilized cells of Nicotiana tabacum. AB - The biotransformation of decanones with immobilized cells of Nicotiana tabacum led to the formation of their corresponding alcohols of high optical purity. PMID- 24240400 TI - Cold induced gene expression in Arabidopsis thaliana L. AB - Exposure of Arabidopsis thaliana L. to an acclimation temperature (+4 degrees C) results in a rapid increase of frost tolerance from -3 degrees C to -7 degrees C. This increase could be correlated to changes in soluble protein pattern. Analysis of in vitro translation products from isolated mRNA suggests that induction acts at the transcriptional level. PMID- 24240401 TI - Comparative analysis of free DNA delivery and expression into protoplasts of Panicum maximum Jacq. (Guinea grass) by electroporation and polyethylene glycol. AB - Relative levels of gene expression were studied in protoplasts isolated from two cell lines of Panicum maximum following DNA delivery by electroporation and polyethylene glycol (PEG). Gene expression was evaluated by assaying for chloramphenicol acetyltransferase (CAT) activity expressed by the CaMV 35S promoter with a nopaline synthase 3' polyadenylation signal, approximately 48 hours after DNA delivery. The expression of the CAT gene was slightly higher in electroporated protoplasts in comparison to PEG mediated delivery. However, PEG treated protoplasts showed higher plating efficiency. The effect of different salts and the molecular weight of PEG used on gene expression was also studied. PMID- 24240402 TI - Transformation and regeneration of Brassica oleracea mediated by an oncogenic Agrobacterium tumefaciens. AB - A chimaeric neomycin phosphotransferase II (NPT II) gene was introduced in Brassica oleracea using an oncogenic strain of Agrobacterium tumefaciens harbouring Ti plasmid which contains Nos/NPTII in its T-DNA. The transformation of B. oleracea with the oncogenic Ti plasmid, resulted in regeneration of shoots and roots without any exogenous requirement of phytohormones. The presence of NPT II gene was determined by hybridization of Tn5 encoded NPT II gene with DNA of kanamycin resistant regenerated plants. The expression of NPT II was demonstrated by kanamycin phosphorylation assay. Several regenerated plants were obtained, a few of them were found to be morphological variants and a chlorophyll deficient mutant plant was also obtained. PMID- 24240403 TI - Examination of triterpenoids produced by callus and cell suspension cultures of Glycyrrhiza glabra. AB - Callus and cell suspension cultures of Glycyrrhiza glabra failed to produce detectable amounts of glycyrrhizin, the major oleanane-type triterpene glycoside of the thickening root, or of its 11 -deoxoderivative. However, betulinic acid, a lupane-type triterpene, which was found in the root bark, and a small amount of beta-amyrin, a possible precursor of oleanane-type triterpenes, were detected in cell suspension cultures in addition to lupeol, a fundamental form of lupane-type triterpenes. These findings suggest that the absence of glycyrrhizin in undifferentiated cultured cells may be partly due to interruption of the later reactions leading to the synthesis of glycyrrhizin from a triterpenoid intermediate. PMID- 24240404 TI - Parameters affecting the frequency of kanamycin resistant alfalfa obtained by Agrobacterium tumefaciens mediated transformation. AB - Kanamycin resistant plants of Medicago varia A2 were obtained by an optimized procedure for high frequency transformation using Agrobacterium tumefaciens infection of leaf and petiole tissue. Parameters which affected the frequency were explant type, the Agrobacterium strain used and the time allowed for cocultivation. Under optimum conditions, i.e., using the Agrobacterium strain A281 and a 4 day cocultivation period, the frequency of transformed leaflets obtained was greater than 70%. PMID- 24240405 TI - Soybean somatic embryogenesis: interactions between sucrose and auxin. AB - The interaction between sucrose and auxin in soybean (Glycine max L. Merr.) somatic embryogenesis was investigated by culturing immature cotyledon explants on factorial combinations of NAA (6.25, 12.5, 25 and 50 mg/l) and sucrose (0.5, 1, 2 and 4%). A significant interaction between sugar and auxin was observed; balanced concentrations of the two components were required for optimal embryo production and normality. The highest numbers of normal somatic embryos were produced on media which contained combinations of low to intermediate levels of sucrose (1 or 2%) and NAA (6.25 or 12.5 mg/l). Cotyledon explants from induction media having a low (0.5%) sucrose content showed the most efficient embryogenesis in secondary culture. The highest frequencies of germination (32 to 41%) were seen among embryos induced on media containing 0.5% sucrose. PMID- 24240406 TI - Improved sensitivity of genetic complementation of nitrate reductase deficient mutants via protoplast fusion. AB - An improved rapid assay for complementation testing of mutants of Nicotiana tabacum deficient in nitrate reductase is described. The test is based on measurement of in vivo nitrate reductase activity in 7 to 10 day old cultures derived from fusion-treated protoplast mixtures of the respective mutants as a criterion for complementation. It allows to detect complementing hybrids induced by the conventional droplet fusion technique in small numbers of protoplasts per assay (8*10(4)). PMID- 24240407 TI - Comparative shoot regeneration responses of diploid brassicas and their synthetic amphidiploid products. AB - Comparative shoot regeneration responses of three diploid Brassica species, B. campestris (AA), B. nigra (BB) and B. oleracea (CC) and their synthetic amphidiploid combinations have been investigated. The study indicates that A genome has an inhibitory effect on regeneration as evident from significantly low responses of B. juncea (AABB) and B. napus (AACC) combinations, in comparison with regeneration response of B. nigra and B. oleracea. This inhibition may arise from genomic interactions or from the B. campestris cytoplasm interacting negatively with the alien genome. Significant cytoplasmic influence on regenerability has been observed in B. carinata (BBCC) synthesised from reciprocal crosses of B. nigra and B. oleracea. PMID- 24240408 TI - Use of cell culture to screen sunflower germplasm for resistance to Phomopsis brown/gray stem spot. AB - Resistance to Phomopsis sp. (Diaporthe sp.) brown/gray stem spot was confirmed by screening sunflower calli on shoot induction media amended with fungal filtrate. Calli of sunflower genotypes OCMS 74 and NS-H-45, which show resistance to the disease in field trials, remained viable on media with 15% (v/v) fungal filtrate, while calli of field susceptible genotypes RHA 273 and PAG/SF 103 were killed on media with as little as 7.5% fungal filtrate. Fresh weight of calli of all genotypes was significantly reduced by 2.5% fungal filtrate, and calli of all genotypes were killed by filtrate concentrations of 20%. These in vitro results corroborate prior field observations for disease reaction of these genotypes. PMID- 24240409 TI - Protoplast isolation and callus production from leaves of tissue-cultured Vitis spp. AB - Protoplasts were isolated from mesophyll of axenic cultures of grape, Vitis rotundifolia cv. Summit and V. vinifera cv. Cabernet Sauvignon. Enzymes effective for protoplast isolation were Macerozyme R-10 (0.5% and 0.1%) and Cellulase Onozuka R-10 (1.0% and 0.5%) for V. rotundifolia and V. vinifera, respectively. Polyvinylpyrrolidone and 2-(N-morpholino)ethanesulfonic acid were essential in the isolation media. Protoplasts were purified using flotation/centrifugation. The protoplasts of V. rotundifolia cultured in Gamborg's B5 basal medium with 2.2 MUM 6-benzyladenine, 4.5 MUM 2,4-dichlorophenoxyacetic acid and 0.4% agarose gave the best plating efficiency of conditions tried in this study. Cell division occurred within 5 to 6 days and visible microcalli developed within one month. After 6 weeks in culture, microcalli transferred to liquid medium exhibited active callus growth. Protoplasts of V. vinifera cultured under these conditions had similar results. PMID- 24240410 TI - Production of pineapple plants in vitro. AB - In vitro culture of pineapple (Ananas comosus) was studied to determine the efficiency of axillary bud culture for rapid propagation of several cultivars. The technique used maximizes the success rate of various steps in the production of pineapple plants. Rapid mass multiplication of plantlets started 9 months after explanting with a significant log phase. The number of plantlets obtained from the culture of a single bud by the thirteenth month ranged from 210 to 380 for 'Perolera'; 300 to 350 for 'PR-1-67'; and 40 to 85 for 'Smooth Cayenne'. The method permits culture of a range of pineapple cultivars. Little morphological variation was observed in young regenerated plants. PMID- 24240411 TI - Occurrence and frequency of precocious germination of somatic embryos is a genotpye - dependent phenomenon in wheat. AB - Immature embryos of thirty-three genotypes of wheat were cultured on 2,4-D containing medium. Occurrence of precocious germination of the zygotic and somatic embryos simultaneously on the same medium was a striking feature observed during the course of work. The percentage of precocious germination was seen to vary extensively from 0-88% and 0-84% for zygotic and somatic embryos respectively. In the genotypes NI-5439 and NI-5643 which are characterized by a high tillering capacity, the phenomenon of precocious germination seems to take a different path from that observed in the other genotypes. This is evident since these two genotypes require total absence of hormone for shoot elongation although multiple shoot primordia are formed on auxin containing medium.Precocious germination also seems to be relevant to somatic embryogenesis and plantlet regeneration. This conclusion stems from the observation that a majority of the genotypes that show precocious germination of zygotic embryos have greater embryogenic potential. Consecutively, most of the genotypes that show precocious germination of somatic embryos exhibit a higher frequency and faster rate of plantlet regeneration. PMID- 24240412 TI - Transgenic antibiotic resistance may be differentially silenced in germinating pollen grains. AB - Transgenic tobacco (Nicotiana tabacum L.) plants, carrying the neomycin phosphotransferase (NPT II) gene from E. coli, are resistant to kanamycin when grown from seeds on kanamycin containing medium. Tissue and cell cultures derived from those transformants also express resistance and regenerate complete plantlets in the presence of the antibiotic. This unspecific response to the selective condition has led to the belief that the foreign gene is continuously active or uniformly inducible in all cells of the transgenic plant. However, our experiments show that this view is not true for pollen grains during in vitro germination. Pollen grains isolated from kanamycin resistant tobacco plants carry and transmit the foreign gene but do not express resistance when germinating in vitro. This data presents evidence for differential silencing of a foreign gene in a mature gamete. On the other hand, immature pollen grains (microspores) appear to express resistance. The point of the downregulation of the neomycin transferase gene during pollen maturation is discussed. PMID- 24240413 TI - In vitro meristem cloning of Eucalyptus tereticornis Sm. AB - Rapid multiplication of axillary meristems and direct shoot development occurred from nodal explants of mature Eucalyptus tereticornis Sm. with 5.3 MUM NAA, 1.1 MUM IAA and 4.4 MUM BA in Murashige-Skoog medium. Repeated subcultures of the second generation shoot cultures into low cytokinin-auxin containing media (0.44 0.88 MUM BA+0.1 MUM NAA) yielded axillary microshoots in large numbers. Half strength MS liquid medium with 4.9 MUM IBA, 5.5 MUM IAA and 5.3 MUM NAA for four days, half-strength semi-solid hormonefree MS medium with charcoal, and MS liquid medium without charcoal and hormones, in sequence, induced rooting of shoots in the dark. This system is suitable for the mass propagation of this difficult-to root eucalypt. PMID- 24240414 TI - Somatic embryogenesis and plant regeneration in embryo cultures of Euterpe edulis mart. (palmae). AB - The induction of somatic embryogenesis in embryo cultures of Euterpe edulis is described. The basal medium was composed of LS salts and Morel & Wetmore vitamins. Activated charcoal was added to prevent explant oxidation. 2,4-D higher than 50 mg/l was necessary for inducing embryogenesis which occurs 45-180 days after the start of cultures. Embryos arise directly from surface proliferating tissues on the matrix structure , without callus formation. The transfer of tissues with embryo clusters to medium with NAA plus 2iP, or without growth regulators, induces embryo development into plantlets. PMID- 24240415 TI - Anthocyanin production in callus cultures of roselle (Hibiscus sabdariffa L.). AB - Callus tissues derived from seedlings of roselle (Hibiscus sabdariffa L.) were shown to produce two cyanidin glycosides as major anthocyanin pigments. Both callus growth and anthocyanin synthesis were remarkably stimulated by 2,4 dichlorophenoxyacetic acid. The highest anthocyanin yield was observed when 1 MUM 2,4-D in combination with 0.1-1 MUM kinetin was supplemented to the culture medium. In contrast, gibberellic acid showed inhibitory effect on anthocyanin production. PMID- 24240416 TI - Callus induction and high frequency plant regeneration in Italian millet (Setaria italica). AB - Callus was induced from mature seeds of two cultivars of Setaria italica (L.) on Murashige and Skoog's medium (1962) supplemented with 2mg/l 2,4-D and 0.5 mg/l KN. Regenerating ability of the callus was better in the cultivar 315 compared to 212. Organogenesis was influenced not only by cytokinin, but also by the sucrose concentration in the medium. High frequency (80%) plant regeneration was achieved and quantified on the basis of callus fresh weight. The ability of the callus (cultivar 212) to regenerate whole plants was retained until the 5th passage, but during the 6th passage it declined considerably. PMID- 24240417 TI - Induction of pollen plantlets in rice by spikelet culture. AB - Induction of pollen callus and subsequent regeneration of plantlets from the callus have been achieved from rice spikelets cultured in a liquid medium containing sucrose, alpha-naphthalene-acetic acid and kinetin. When spikelets are cultured in a medium containing 6% sucrose, calluses are released into the medium where they continue to increase in size without undergoing organogenesis. On the other hand, in a medium containing 2% sucrose, calluses are retained within the anther locule where they differentiate into plantlets. Cytological studies have shown that calluses have their origin either in the vegetative cell of asymmetrically dividing pollen grains or in both cells of pollen grains which divide more or less equally. PMID- 24240418 TI - Tissue, cell culture and micropropagation of Mandevilla velutina, a natural source of a bradykinin antagonist. AB - Leaf, stem and root explants of Mandevilla velutina were cultured in vitro and produced vigorous callus in LS basal medium containing one auxin (2,4-D or NAA) plus BAP. Calli can be subcultured indefinitely with vigorous growth. Subculture of calli to NAA (1.0 mg/l) plus BAP (5.0 mg/l) caused profuse regeneration of shoots. Isolated shoots were rooted in basal medium plus NAA (5.0 mg/l) or IBA (8.0 mg/l). Rapidly growing cell suspensions can be easily obtained from friable callus cultured in liquid medium. PMID- 24240419 TI - Regeneration of plantlets from cell suspension culture derived callus of white poplar (Populus alba L.). AB - Friable calli derived from the stem tissues of Populus alba were used to establish cell suspension cultures which were characterized for in vitro growth and regeneration capacity. Suspended cells and callus recovered from these cells were maximal on a fresh weight basis using MS liquid medium containing 0.44 MUM BAP and 4.52 MUM 2,4-D. Shoot regeneration from the recovered callus was observed within 30 to 40 days of culture. The number of shoots was increased by subculturing the shoot-forming callus 2 to 3 times on MS medium supplemented with 19.7 MUM 2iP and 0.05 MUM IBA. Regenerated shoots were easily rooted on half strength MS medium lacking growth regulators, and the plantlets were transferred to pots containing vermiculite for greenhouse growth. PMID- 24240420 TI - Genetic analysis of T-DNA insertions into the tobacco genome. AB - A genetic test was performed on seeds from 283 transgenic tobacco plants obtained by T-DNA transformation. Seeds from self-fertilized transgenic plants were germinated on kanamycin-containing medium, and the percentage of seeds which germinated, as well as the ratio of kanamycin-resistant to kanamycin-sensitive seedlings were scored. Nine categories of transformants could be distinguished according to the number of loci into which T-DNA had inserted, and according to the effects of T-DNA integration on seed or seedling development. In most of the plants, T-DNA was inserted into a single site; others contained multiple independent copies of T-DNA. The number of T-DNA integration sites was found to be independent of whether a binary vector system or a cointegrate Ti plasmid had been used to obtain the transgenic plant. Loss of marker genes or marker gene expression from generation to generation appeared to be a quite frequent event. Plants which appeared to be insertional recessive embryo-lethal mutants did not exhibit this trait in the next generation. PMID- 24240421 TI - The animal ether phospholipid platelet-activating factor stimulates acidification of the incubation medium by cultured soybean cells. AB - Addition of the animal ether phospholipid platelet-activating factor, 1-0-alkyl-2 acetyl-sn-glycero-3-phosphocholine, (PAF) stimulates medium acidification in cultured soybean (Glycine max L.) cells. The pH of the medium after 8-10 hours is on the average one pH unit lower than in controls. With fusicoccin an average pH difference of 1.7 units is reached. Phospholipids, glycerol, 1-oleyl-2-acetyl-sn glycerol, 1-0-hexadecyl-sn-glycerol, and triolein at the same concentrations as PAF had no stimulatory effect on medium acidification. The detergents CHAPS and deoxycholate lead to alkalinization of the medium whereas lysophosphatidylcholine (LPC), a detergent with structural similarity to PAF, shows no effect. PMID- 24240422 TI - A plant protein kinase and plant microsomal H(+) transport are stimulated by the ether phospholipid platelet-activating factor. AB - ATP-dependent H(+) transport in microsomes from zucchini hypocotyls is stimulated by the ether lipid 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor = PAF) known as a hormone-like substance from mammals. The stimulation can only be observed when soluble cytosolic proteins are present. A soluble protein mediating the PAF-dependent H(+) transport and a PAF-stimulated protein kinase are coeluted by DEAE-Sephacel chromatography. Stimulation of phosphorylation by PAF of a 55 kDa polypeptide without Ca(2+) and, additionally, of a 35 kDa polypeptide in the presence of Ca(2+) is observed in zucchini microsomal membranes. This is evidence for a novel phospholipid-stimulated protein kinase in plants. Phosphorylation of regulatory proteins may be involved in the stimulation of in vitro H(+) transport by PAF. PMID- 24240423 TI - High efficiency Agrobacterium tumefaciens-mediated transformation of Arabidopsis thaliana leaf and cotyledon explants. AB - A highly efficient and fast Agrobacterium-mediated leaf disc transformation system for the Arabidopsis thaliana L. genotype C24 was developed. This protocol is also amenable to other ecotypes - as could be shown for Landsberg erecta and Wassllewskija. Besides the hygromycin selection also the G418 and kanamycin selection were established. Furthermore the described procedure is appliable not only to leaf explants but also to expanded cotyledons which proved to be an excellent alternative as explant source for transformation experiments. PMID- 24240424 TI - Plant regeneration from mesophyll protoplasts of Williams' Bon Chretien (syn. Bartlett) pear (Pyrus communis L.). AB - Leaf protoplasts of axenic shoot cultures of Pyrus communis L. cv. Williams' Bon Chretien (syn. Bartlett) underwent cell wall regeneration and division to give multicellular colonies in a modified Murashige and Skoog medium which lacked ammonium ions, but supplemented with 1-naphthaleneacetic acid (NAA), 4-indole-3yl acetic acid, 6-benzylaminopurine (BAP) and casein hydrolysate. Protoplast-derived colonies gave callus on Murashige and Skoog salts medium with NAA and BAP and exhibited shoot regeneration on half-strength Murashige and Skoog medium supplemented with 0.2 mg 1(-1) 4-indole-3yl-butyric acid, 2.0 mg 1(-1) BAP, 0.2 mg 1(-1) gibberellic acid, 50 mg 1(-1) casein hydrolysate and 10 mg 1(-1) Ca pantothenate. Following rooting, protoplast-derived plants of pear were transferred to the glasshouse where they completed acclimatization. PMID- 24240425 TI - Root induction on several Solanaceae species by Agrobacterium rhizogenes and the determination of root tropane alkaloid content. AB - Using Agrobacterium rhizogenes, roots were induced on explants of 24 different Solanaceae species and established as in vitro cultures. Some of the root clones produced tropane alkaloids at levels similar to roots of the corresponding intact plants and maintained these levels over several passages. PMID- 24240426 TI - Somatic embryogenesis in Sitka spruce (Picea sitchensis (Bong.) Carr.). AB - Embryonal-suspensor masses from immature embryos from cones of Sitka spruce (Picea sitchensis (Bong.) Carr.) proliferated on a modified Murashige & Skoog medium with N(6)-benzyl-aminopurine, kinetin, 2,4-dichlorophenoxyacetic acid and an organic nitrogen source. The slimy white embryonal-suspensor masses with proembryos were maintained on a solid proliferation medium with reduced amounts of growth regulators. Transfer of embryonal-suspensor masses to a non-woven polyester carrier with liquid maturation media containing +/-2-cis-4-trans abscisic acid and a reduced amount of inositol and organic nitrogen resulted in synchronized embryo formation. Further development was achieved on a medium without +/-2-cis-4-trans-abscisic acid and organic nitrogen. Somatic embryos were successfully transferred ex vitrum. PMID- 24240427 TI - Assay of plant proteins with bicinchoninic acid for high resolution two dimensional polyacrylamide gel electrophoresis. AB - A method is described for estimating proteins in the same plant tissue sample that is solubilized for separation by two-dimensional polyacrylamide gel electrophoresis. The method uses a modified bicinchoninic acid (BCA) protein assay procedure and a modified standard urea solubilization buffer to estimate microgram values of unknown protein concentration, in the presence of 9 M urea and 4% Nonidet P-40, from a linear standard curve. A method for a quantitative determination of protein concentration by BCA in a sample containing 9 M urea and 4% Nonidet P-40 is also described. This method is effective for the determination of proteins in minute non-green and green plant tissue, and is especially designed for vegetative and floral shoot apices, and the primordia of inflorescences. PMID- 24240428 TI - Immunogenicity and safety of an inactivated 2012/2013 trivalent influenza vaccine produced in mammalian cell culture (Optaflu(r)): an open label, uncontrolled study. AB - BACKGROUND: The present study aimed to evaluate immunogenicity and safety of the 2012/2013 seasonal influenza vaccine (Optaflu((r))) after the World Health Organization recommended two new strains for the composition. RESULTS: Twenty-one days post-vaccination geometric mean titers (GMTs) against A(H1N1), A(H3N2) and the B strain were 528, 935, and 201 for adults and 272, 681, and 101 for elderly subjects, respectively. The proportion of subjects with a HI titer of >= 40 against the three strains A(H1N1), A(H3N2) and B was 98%, 100%, and 98% in adults and 100%, 100%, and 85% in elderly subjects, respectively. Optaflu((r)) met the CHMP criteria of the Committee for Medicinal Products for Human Use (CPMP/BWP/214/96). Pre-vaccination titers indicated seroprotection against the A(H1N1), the A(H3N2) and the B strain in 56%, 86%, and 54% of the adults and in 61%, 85%, and 40% of the elderly with highest titers against the A(H3N2) strain. In the safety analysis injection site pain (37%) and myalgia (31%) were the most common local and systemic reactions. No serious adverse events were recorded. CONCLUSION: The 2012/2013 seasonal influenza vaccine Optaflu((r)) showed good immunogenicity and an acceptable safety profile in both adults and elderly. METHODS: In this trial, 126 subjects (63 adults >=18 to <=60 y, 63 elderly >=61 y) were vaccinated with a single dose Optaflu((r)) containing each of the three virus strains recommended for the 2012/2013 season (A/California/7/2009(H1N1) like strain, A/Victoria/361/2011(H3N2)-like strain, and B/Wisconsin/1/2010-like strain). Immunogenicity was assessed by hemagglutinin inhibition (HI) and single radial hemolysis (SRH) assays on day 22, the safety profile was investigated throughout the whole study period. PMID- 24240429 TI - Detecting the translocation of DNA through a nanopore using graphene nanoribbons. AB - Solid-state nanopores can act as single-molecule sensors and could potentially be used to rapidly sequence DNA molecules. However, nanopores are typically fabricated in insulating membranes that are as thick as 15 bases, which makes it difficult for the devices to read individual bases. Graphene is only 0.335 nm thick (equivalent to the spacing between two bases in a DNA chain) and could therefore provide a suitable membrane for sequencing applications. Here, we show that a solid-state nanopore can be integrated with a graphene nanoribbon transistor to create a sensor for DNA translocation. As DNA molecules move through the pore, the device can simultaneously measure drops in ionic current and changes in local voltage in the transistor, which can both be used to detect the molecules. We examine the correlation between these two signals and use the ionic current measurements as a real-time control of the graphene-based sensing device. PMID- 24240430 TI - Spin Hall effect clocking of nanomagnetic logic without a magnetic field. AB - Spin-based computing schemes could enable new functionalities beyond those of charge-based approaches. Examples include nanomagnetic logic, where information can be processed using dipole coupled nanomagnets, as demonstrated by multi-bit computing gates. One fundamental benefit of using magnets is the possibility of a significant reduction in the energy per bit compared with conventional transistors. However, so far, practical implementations of nanomagnetic logic have been limited by the necessity to apply a magnetic field for clocking. Although the energy associated with magnetic switching itself could be very small, the energy necessary to generate the magnetic field renders the overall logic scheme uncompetitive when compared with complementary metal-oxide semiconductor (CMOS) counterparts. Here, we demonstrate a nanomagnetic logic scheme at room temperature where the necessity for using a magnetic field clock can be completely removed by using spin-orbit torques. We construct a chain of three perpendicularly polarized CoFeB nanomagnets on top of a tantalum wire and show that an unpolarized current flowing through the wire can 'clock' the perpendicular magnetization to a metastable state. An input magnet can then drive the nanomagnetic chain deterministically to one of two dipole-coupled states, '2 up 1 down' or '2 down 1 up', depending on its own polarization. Thus, information can flow along the chain, dictated by the input magnet and clocked solely by a charge current in tantalum, without any magnetic field. A three to four order of magnitude reduction in energy dissipation is expected for our scheme when compared with state-of-the-art nanomagnetic logic. PMID- 24240431 TI - Graphene mechanical oscillators with tunable frequency. AB - Oscillators, which produce continuous periodic signals from direct current power, are central to modern communications systems, with versatile applications including timing references and frequency modulators. However, conventional oscillators typically consist of macroscopic mechanical resonators such as quartz crystals, which require excessive off-chip space. Here, we report oscillators built on micrometre-size, atomically thin graphene nanomechanical resonators, whose frequencies can be electrostatically tuned by as much as 14%. Self sustaining mechanical motion is generated and transduced at room temperature in these oscillators using simple electrical circuitry. The prototype graphene voltage-controlled oscillators exhibit frequency stability and a modulation bandwidth sufficient for the modulation of radiofrequency carrier signals. As a demonstration, we use a graphene oscillator as the active element for frequency modulated signal generation and achieve efficient audio signal transmission. PMID- 24240432 TI - Engineering myosins for long-range transport on actin filaments. AB - Cytoskeletal motors act as cargo transporters in cells and may be harnessed for directed transport applications in molecular detection and diagnostic devices. High processivity, the ability to take many steps along a track before dissociating, is often a desirable characteristic because it allows nanoscale motors to transport cargoes over distances on the scale of micrometres, in vivo and in vitro. Natural processive myosins are dimeric and use internal tension to coordinate the detachment cycles of the two heads. Here, we show that processivity can be enhanced in engineered myosins using two non-natural strategies designed to optimize the effectiveness of random, uncoordinated stepping: (1) the formation of three-headed and four-headed myosins and (2) the introduction of flexible elements between heads. We quantify improvements using systematic single-molecule characterization of a panel of engineered motors. To test the modularity of our approach, we design a controllably bidirectional myosin that is robustly processive in both forward and backward directions, and also produce the fastest processive cytoskeletal motor measured so far, reaching a speed of 10 um s(-1). PMID- 24240433 TI - Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer. AB - Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB 231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of (18)F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the "in vivo" relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer. PMID- 24240434 TI - [Dependence receptors: life or death choices]. AB - Whereas the classic dogma postulates that transmembrane receptors remain inactive at the plasma membrane unless bound by their specific ligand, it was suggested that some receptors may actually be active not only in the presence of their ligand, but also in their absence. In this latter case, the signaling downstream of these unbound receptors leads to apoptosis. These receptors were consequently named dependence receptors, as their cell expression renders the survival of the cell dependent on the presence in the cell environment of its respective ligand. This dual function - positive in the presence of ligand, negative in the absence of ligand - is hypothesized to lead these receptors to have key roles both during embryonic development and in the regulation of tumorigenesis. In the context of cancer, the hypothesis is that these receptors are tumor suppressors that would limit tumor progression by inducing apoptosis of tumor cells outside of settings of ligand accessibility/availability. This was recently formally demonstrated for the prototypical dependence receptors that bind netrin-1- i.e., DCC and UNC5H. Because expression of DCC and UNC5H is a constraint for tumor progression, their expression is often lost in many aggressive cancers. However, a loss of dependence receptors is not always the selective advantage used by tumor cells to escape this survival dependence on the presence of the ligand. Indeed, it was shown that in many cancers, tumor cells acquire the preferred autocrine expression of ligands of dependence receptor. This selective advantage for the tumor is much more appealing in terms of therapeutic opportunities. Drugs based on the interference on the interaction between dependence receptors and their ligands allow tumor cell death in vitro and trigger tumor growth and metastases inhibition in mice. This review describes how a basic cell biology concept has provided in a near future new tools to fight cancer. PMID- 24240435 TI - Epidemiology of cardiovascular risk factors in Asian countries. AB - The distribution and burden of 5 conventional risk factors (elevated blood pressure, high total cholesterol, diabetes, obesity/overweight and smoking) for cardiovascular diseases (CVD) were reviewed in 10 selected Asian countries, in addition to the United Kingdom and the United States. Over the past 3 decades, age-standardized systolic blood pressure was on the decline in high-income countries but on the rise in low- to middle-income countries. Similar patterns were observed for total cholesterol levels, although the absolute levels remained higher in high-income countries. A pronounced increase in the prevalence of diabetes mellitus was seen in most of the Asian countries, corresponding to an increase in the levels of body mass index. The number of smokers declined markedly with time, particularly in men, in some selected Asian countries (Japan, Singapore, China, Vietnam). However, the prevalence of current smokers for all countries in 2011 remained excessive. The population-attributable risks for stroke and ischemic heart were highest for high blood pressure, followed by total cholesterol, obesity, and smoking. Evidence suggests that in both Asia and the West, no country is in sufficient control of any of these factors and that intervention programs to alter their effect on CVD are of equal importance. PMID- 24240436 TI - Fragmented QRS wave as a marker of cardiac events in various cardiac diseases. PMID- 24240438 TI - Orthopaedics in the dawn of civilisation, practices in ancient Egypt. PMID- 24240437 TI - Erythrocyte membrane docosapentaenoic acid levels are associated with islet autoimmunity: the Diabetes Autoimmunity Study in the Young. AB - AIMS/HYPOTHESES: We previously reported that lower n-3 fatty acid intake and levels in erythrocyte membranes were associated with increased risk of islet autoimmunity (IA) but not progression to type 1 diabetes in children at increased risk for diabetes. We hypothesise that specific n-3 fatty acids and genetic markers contribute synergistically to this increased risk of IA in the Diabetes Autoimmunity Study in the Young (DAISY). METHODS: DAISY is following 2,547 children at increased risk for type 1 diabetes for the development of IA, defined as being positive for glutamic acid decarboxylase (GAD)65, IA-2 or insulin autoantibodies on two consecutive visits. Using a case-cohort design, erythrocyte membrane fatty acids and dietary intake were measured prospectively in 58 IA positive children and 299 IA-negative children. RESULTS: Lower membrane levels of the n-3 fatty acid, docosapentaenoic acid (DPA), were predictive of IA (HR 0.23; 95% CI 0.09, 0.55), while alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not, adjusting for HLA and diabetes family history. We examined whether the effect of dietary intake of the n-3 fatty acid ALA on IA risk was modified by fatty acid elongation and desaturation genes. Adjusting for HLA, diabetes family history, ethnicity, energy intake and questionnaire type, ALA intake was significantly more protective for IA in the presence of an increasing number of minor alleles at FADS1 rs174556 (pinteraction = 0.017), at FADS2 rs174570 (pinteraction = 0.016) and at FADS2 rs174583 (pinteraction = 0.045). CONCLUSIONS/INTERPRETATION: The putative protective effect of n-3 fatty acids on IA may result from a complex interaction between intake and genetically controlled fatty acid desaturation. PMID- 24240439 TI - Childhood asthma: recent developments and update. AB - PURPOSE OF REVIEW: The purpose of this review is to provide an update on childhood asthma specifically related to the underlying genetic background and pathophysiology of asthma and their interaction with environmental stimuli. We will also discuss emerging data in the field of disease phenotyping. RECENT FINDINGS: The field of genetics is continuously evolving to expand our knowledge on the cause of disease. Childhood onset asthma has been related to atopy and exposure to early-life infections. More recently, phenotypes have been used to classify asthma as transient and persistent, but the association of each phenotype with the genetic origin of asthma is not clearly understood. SUMMARY: This review covers the topics of genetics, epigenetics, pathophysiology, phenotypes and treatment as they relate to childhood asthma. Overall, it provides a basis for the future of asthma treatment through description of the current research. PMID- 24240440 TI - Effect of cytokinin on morphological changes of suspension cultured cells of the moss, Barbula unguiculata. AB - Suspension cultured cells of the moss, Barbula unguiculata, grow actively in both light and dark culture. Light-grown cells contain chlorophyll and exhibit an undifferentiated callus form. When cells are transferred to a dark condition, they develop into protonemata. Protonemata formation in the dark can be inhibited by the addition of 5 MUM benzyladenine or 6-furfurylaminopurine but is not affected by the addition of 5 MUM 2,4-dichlorophenoxyacetic acid or naphthalene acetic acid. PMID- 24240442 TI - Recovery of transgenic plants from "escape" shoots. AB - The problem of escapes is well known to those investigating the regeneration of transgenic shoots from transformed callus. Shoots can pass various tests and assays for transformation, and are then scored as transgenic, but the progeny do not express the transferred trait and do not contain the T-DNA. Explanations for these enigmatic "escapes" include instability of the T-DNA, genomic rearrangements during meiosis, or merely non-rigorous selection or identification assays giving rise to spuriously positive scorings. At least some shoots, however, are likely to simply be chimeric, containing both transformed and non transformed cell lines. In this case, the transformed cells are responsible for the positive selection and scoring on tests, but either do not contribute to the germ line (resulting in no transgenic progeny) or contribute to only a portion of the germ line (resulting in many fewer positive segregants than expected). We describe two methods which we used to recover fully transgenic plants from apparent escapes. One method involved analyzing more progeny than would normally be necessary (to identify minority transgenic contribution to the cell line). The other method, (to recover transgenic plants from primary selectants with no transgenic contribution to the germ line) involved regenerating new shoots from leaf tissue used in a selection assay to score the initial shoot as a positive transgenic. PMID- 24240441 TI - Biotransformation of nicotine alkaloids by tobacco shooty teratomas induced by a Ti plasmid mutant. AB - Tobacco shooty or rooty teratomas and hairy roots were induced by Agrobacterium tumefaciens (pGV 3845), A. tumefaciens (pGV 3304) and A. rhizogenes (pRi 8196), respectively. The tobacco alkaloids, nicotine, nornicotine and anatabine, were produced in hairy roots and in rooty teratomas but not in shooty teratomas. However, the shooty teratomas have the ability to accumulate the alkaloids and to biotransform nicotine to nornicotine. These were established by co-culture experiments incubating hairy roots and shooty teratomas in a same dish and by biotransformation experiments with shooty teratomas. PMID- 24240443 TI - Recovery of primary transformants of soybean. AB - Three transformants of soybean, Glycine max (L.) Merr., have been recovered among a total of 18 plants regenerated by somatic embryogenesis from immature cotyledon tissues after cocultivation with Agrobacterium strains carrying a 15 kD zein gene (pH5PZ3D). DNA from upper leaves hybridized to a synthetic RNA probe specific for the zein sequence at a level equivalent to at least one copy per haploid genome. Hybridization to a vir G/C probe, however, was negligible, indicating that sequestration of whole bacteria or even persistence of plasmids within the tissues could not account for the zein hybridization signals. Progeny of all plants were uniformly untransformed. Since most somatic embryos have a multicellular origin in the regeneration system used, it is believed that the primary transformants were chimeric. The results indicate that somatic embryogenesis may be adaptable to Agrobacterium-mediated transformation in soybean, but that greater numbers of mitotic cycles under selection before embryo initiation will be required if somatic embryogenesis is to be used efficiently for production of plants with transformed germ-line cells. PMID- 24240444 TI - Plant development from isolated microspores of Zea mays L. AB - This paper reports the development of plants from mechanically isolated microspores of corn (Zea mays). Large populations of corn microspores were isolated using technology previously developed for rapeseed. Embryos and callus were developed from microspores in the late uninucleate stage. Scutellar-type embryos developed after two weeks and these could be transferred and germinated on a hormone free medium. However, the large majority of plants recovered from embryos developed only upon transfer to a corn embryogenic callus medium. These embryos produced shoots through organogenesis, and subsequently could be induced to form roots. Plants were developed from these colonies and grown in the greenhouse. The frequency of mature plants developed from the embryos was approximately 5 %. Non embryogenic callus which developed from some microspores have thus far either failed to develop or have developed only roots. Seed set has been obtained on some of the regenerated plants. PMID- 24240445 TI - Elimination of systemic contamination in explant and protoplast cultures of rubber (Hevea brasiliensis Muell. Arg.). AB - Ten systemic microorganisms (bacteria and yeasts) were isolated from stem sections of ex vitro grown rubber plants. Antibiotics were screened for their efficacy against these microorganisms and for possible tissue phytotoxicity. Erythromycin, nystatin and streptomycin at bactericidal levels were asymptomatic in relation to tissue stress nor was callusing capacity reduced. Contamination of stem explants as used for callus initiation, was reduced from 95.8 to 43.8% by the incorporation of these three antibiotics, at concentrations of 32.0, 16.0, 16.0 MUg/ml respectively. Contamination was eliminated from protoplast cultures by these antibiotics, at half strength, in the plasmolysis and enzyme solutions. Rubber protoplast survival was promoted by these antibiotics. PMID- 24240446 TI - In vitro plant regeneration from leaf and cotyledon explants of Cucumis melo L. AB - Five different genotypes from in vitro as well as greenhouse grown melon plants were shown to be highly responsive for in vitro shoot formation from leaf explants when placed on basic MS medium supplemented with 1 mg/l 6 benzylaminopurine. In addition, a very suitable regeneration system was obtained when cotyledon pieces of mature seeds were incubated on the same culture medium. In this case, the first shoots already appeared after 10 days of incubation, and hundreds of shoots were formed on the cut surface 3 to 4 weeks later. Explants from mature cotyledons derived from seedlings did not lead to any shoot formation. PMID- 24240447 TI - Factors affecting the use of chloramphenicol acetyltransferase as a marker for Brassica genetic transformation. AB - The CAT gene which codes for the enzyme chloramphenicol acetyltransferase was found to be ineffective as a reporter gene in cells and tissues of Brassica species. High levels of endogenous CAT activity were found to be widespread among this genus and did not appear to be distributed in a tissue- or cell-specific manner. Moreover, the presence of an inhibitor of CAT activity was discovered in Brassica napus and Brassica juncea. This inhibitor appeared to act selectively on bacterial CAT in transgenic plants. These findings provided an explanation for difficulties experienced in the detection of transgenic CAT activity in B. napus. PMID- 24240448 TI - Precursor-product relationships of Poly(gamma-glutamylcysteinyl)glycine biosynthesis in Datura innoxia. AB - Suspension cultures of Datura innoxia cells were pulse-labeled with [(35)S]cysteine, then exposed to Cd to determine whether there is a direct precursor-product relationship amongst the different forms of the Cd-induced polypeptides, poly(gamma-glutamylcysteinyl)glycines [(gammaEC)nG, n=2 to 5]. Degradation of the polypeptides and possible regeneration of the [(35)S]-labeled glutathione and cysteine pools were also examined. After 2 h of exposure to [(35)S]cysteine, about 70% of the [(35)S]cysteine in the soluble fraction of the cell was incorporated into [(35)S]glutathione before exposure of the cells to Cd. One h after Cd exposure, most of the cellular [(35)S]glutathione was depleted and label was incorporated into (gammaEC)nG. Analysis of [(35)S](gammaEC)nG by reverse phase HPLC showed no direct precursor-product relationship between the synthesis of the shorter and longer chain forms. However, the rate of synthesis of the different polypeptides was linear for 32 h after Cd exposure. There was no evidence of degradation of [(35)S](gammaEC)nG nor was it excreted into the medium within this period. From these results it is suggested that in the presence of Cd, a large pool of (gammaEC)nG is unavailable for elongation to (gammaEC)n+1G. PMID- 24240449 TI - Identification of viruses infected in Rehmannia glutinosa Libosch. var purpurea Makino and effect of virus infection on root yield and iridoid glycoside contents. AB - Virus free plants of Rehmannia glutinosa Libosch. var. purpurea Makino were obtained through meristem tip tissue cultures from plants infected with a mixture of tabocco mosaic virus(TMV), a member of the carlavirus group, and an unknown spherical virus. The re-infection rate of the virus free plants by TMV in the field was determined by enzyme linked immunosorbent assay(ELISA). Twenty seven percent of the plants were re-infected during the first year, 31 % by the end of second year, and 63 % by the end of the third year. The yield of root and iridoid glycoside contents gradually decreased each year. These results led to the conclusion that virus infection causes marked decrease of the yield of roots and productivity of secondary metabolites. PMID- 24240450 TI - Expression of zein in long term cultures of wildtype and opaque-2 maize endosperms. AB - It has been reported that long term cell cultures from maize endosperms are not completely de-differentiated, maintaining some tissue-specific synthesis. We analyzed the expression of zein (the major storage protein of maize seeds) in cultures derived from wildtype and opaque-2 maize endosperms. In wildtype cultures, our data indicate a severe restriction in zein accumulation, resulting both from reduction of transcription and from post-transcriptional events. No detectable zein proteins and trace amounts of transcripts were found in opaque-2 cultures, which do not therefore exhibit a distinctive opaque-2 phenotype. PMID- 24240451 TI - Somatic embryogenesis and plant regeneration in inflorescence and seed derived callus cultures of Poa pratensis L. (Kentucky bluegrass). AB - Callus induction and plant regeneration were studied in 15 cultivars of the facultative apomictic species Poa pratensis L. (Kentucky bluegrass).The tissue culture responses of mature seeds and immature inflorescences were compared. Murashige and Skoog's (MS) medium, supplemented with 2 mg/l 2,4 dichlorophenoxyacetic acid (2,4-D) was used for callus induction and maintenance. Plants could be regenerated from compact and friable callus on MS medium devoid of 2,4-D. Plants were recovered from 14 cultivars at a high frequency (up to 79% of the callus cultures) when young inflorescences were used as the explant material and from only 3 cultivars, at a low frequency (up to 3%), with seeds. Somatic embryos were observed in callus cultures of many cultivars. Fully developed germinating somatic embryos were occasionally observed. Plant regeneration appeared to take place both via somatic embryogenesis and organogenesis. Plants were generally green but albino shoots developed at a low frequency from friable callus. PMID- 24240452 TI - Selection and characterization of an L-thiazolidine-4-carboxylic acid resistant callus culture of Vigna radiata (L.) Wilczek var. radiata. AB - Callus cultures were established from seedling root tips of mungbean (Vigna radiata (L.) Wilczek var. radiata) cv. K 851. The growing calli were exposed to increasing concentrations of thioproline - an analog of proline, in the medium. A concentration of 3.0 mM thioproline completely inhibited the growth of the cells. However, after 25 days incubation 5 cell clones were obtained which could grow on this concentration of thioproline. Out of them one vigorously growing cell clone was further characterized. This selected clone contained higher endogenous levels of free proline (5 fold) and K(+) (1.5 fold) and exhibited elevated tolerance, not only to thioproline but also to exogenously applied NaCl in the growth medium, as compared to the normal sensitive callus cells. Higher endogenous levels of free proline and K(+) appear to impart dual resistance to thioproline and NaCl to the selected cell strain. PMID- 24240453 TI - Growth of Dioscorea deltoidea at high sugar concentrations. AB - Dioscorea deltoidea cell suspension cultures were grown at initial sucrose concentrations of 35 to 200 g/L. The growth rates were similar (about 0.50 day( 1)) with all of the initial sugar concentrations examined. The ratio of fresh weight to dry weight of cells was dependent on the initial sugar concentration, however, it remained fairly constant as long as the sugar was present in the growth medium. These results are different from results recently published, claiming that the growth rate of D. deltoidea cells is dependent on sugar concentration and the fresh weight to dry weight ratio increases throughout growth. PMID- 24240454 TI - The behaviour of tomato golden mosaic virus DNA in cultured cells isolated from systemically infected tobacco leaves. AB - When callus tissue was cultured from leaf pieces taken from a Nicotiana tabacum cv. Xanthi nc. plant systemically infected with tomato golden mosaic virus (TGMV), TGMV-specific DNA persisted for up to 6 months in culture. Analysis of TGMV-specific intracellular DNA forms indicated a decrease in double-stranded relative to single-stranded forms and an increase in sub-genomic relative to genomic single-stranded DNA species in the callus tissue compared to those in the original leaf explant. The implications of the results with regard to TGMV replication are discussed. PMID- 24240455 TI - Genetic transformation of apple (Malus pumila Mill.) using a disarmed Ti-binary vector. AB - The disamed Ti-binary vector pBIN 6 in Agrobacterium tumefaciens has been used in leaf disc transfomations to produce transgenic apple (Malus pumila Mill.) plants with a nomal phenotype except for a somewhat reduced capacity to root. The presence of the genes for nopaline synthase and neomycin phosphotrans ferase (conferring kanamycin resistance), inserted into the host genome by the vector, was confirmed by Southern blot analysis, the detection of nopaline synthase activity and rooting in the presence of the antibiotic.The nopaline synthase gene continued to be expressed in glasshouse-grown plants several months after removal from in vitro growth conditions. PMID- 24240456 TI - Ploidy levels in transgenic tomato plants determined by chloroplast number. AB - We determined germline ploidy of primary tomato transformants by counting meiotic chromosomes. We then determined the number of chloroplasts in stomatal cells by cytological staining. A correlation of these values indicated that diploid transformants had significantly fewer chloroplasts than tetraploid transformants. By maximum likelihood, we estimate that less than 1% of diploid transformants will have chloroplast values in the tetraploid range. Transformed plants generally had more chloroplasts than plants derived from seed. Also, there was more variability between transformed than seed derived plants. Less than 5% of transformed plants were chimeric when comparing leaf and pollen ploidy levels. Of 129 transgenic plants examined, 29 (22%) were polyploid. PMID- 24240457 TI - Somatic embryogenesis and plants from immature zygotic embryos of the species Musa acuminata and Musa balbisiana. AB - Callus was obtained from immature zygotic embryos of semminiferous species (diploids) of Musa sp. using a medium derived from that of Murashige and Skoog. Picloram (7.5 MUM) was added and the medium was solidified with gelrite (2 gl( 1)). Differentiation of the first somatic embryos occurred after transfer of the callus in the presence of 7.5 MUM picloram or 5.3 MUM NAA. Somatic embryos germinated on the medium supplemented with 5.3 MUM NAA. Serial sections of zygotic and somatic embryos showed perfect homology in their structure (epidermis, cotyledonary slit, shoot apex and 3 root primordia). Embryonic callus was characterised by a large quantity of protein storage in the cytoplasm. PMID- 24240458 TI - The use of leaf GPI and IDH isozymes to examine the origin of polyembryony in cultured ovules of seedless grape. AB - Isozyme analysis of young leaf tissue was performed on progeny produced from cultured ovules resulting from crosses of seedless * seedless grapes. Two polymorphic loci, Idh and Gpi-c, were found to segregate in a simple Mendelian fashion in the populations examined. Analyses of 70 seedlings indicated that most seedlings produced by this method were zygotic. Isozyme data of 11 plants from 5 polyembryonic ovules, along with data previously reported, suggest that several mechanisms may be operative in grape that give rise to polyembryony: 1) fertilization and development of more than one cell in the embryo sac, 2) adventive embryogenesis from the zygote, or 3) embryogenic development of gametic cells in addition to the zygote in the embryo sac. PMID- 24240459 TI - High frequency androgenesis from isolated microspores of maize. AB - Anthers from a highly androgenic genotype of maize (139/39-02), when cultured in a modified, liquid YP medium, dehisced within 2-7 days resulting in a stationary suspension of microspores. After 12-15 days, the microspore suspension was found to contain multicellular masses which went on to produce macroscopic embryo-like structures within 20-25 days of culture initiation. Embryogenic callus could be obtained by transferring microspore-derived embryos onto a modified N6 medium supplemented with 2.5 mg/l dicamba and 0.1 mg/l 2,4-D. Subculture onto hormone free medium resulted in plant regeneration. Over 400 embryo-like structures per 100 anthers cultured have been obtained from liquid induction medium as compared to 55 embryos per 100 anthers cultured on an agar-solidified medium. Approximately 5-25% of these embryo-like structures went on to produce callus from which plants could be recovered. Mechanical isolation of microspores from anthers precultured for 0, 3, and 7 days also resulted in embryo production and plant regeneration. This represents the first report of plant recovery from isolated maize microspores. The use of a liquid induction medium applied to a highly androgenic genotype allows for the production of large numbers of microspore-derived plants and provides a single, haploid cell regeneration system for maize. PMID- 24240460 TI - Effect of 1-Aminocyclopropane-1-carboxylic acid and aminoethoxyvinylglycine on ethylene emanation and somatic embryogenesis from orchardgrass leaf cultures. AB - Ethylene emanation rates were assessed from leaf tissues of an embryogenic seed plant (Cycle 0) and regeneration cycle plants selected for enhanced embryogenesis (Cycles I, II and IV). In all experiments, ethylene was assessed from the basal 1 cm portion of the innermost leaf. Ethylene emanation was five-fold higher in Cycle II and Cycle IV plants than in Cycle 0 and nonembryogenic (NE) seed plants. After two days culture on Schenk and Hildebrandt medium containing 30 MUM dicamba (SH-30), ethylene emanation from Cycle 0 and Cycle II leaf sections increased by 55-fold. Culture of leaf explants for 30 days on SH-30 containing 1 mM 1 aminocyclopropane-1-carboxylic acid (ACC) reduced the embryogenic response by 99%. Treatment of leaf explants with 1 mM aminoethoxyvinylglycine (AVG) reduced ethylene emanation but did not affect embryogenesis. The data indicate that ethylene mediated by ACC may hinder the embryogenic response from orchardgrass leaf cultures. PMID- 24240461 TI - Plantlet regeneration from a NaCl-selected salt-tolerant callus culture of Shamouti orange (Citrus sinensis L. Osbeck). AB - Plantlets were regenerated from a selected salt-tolerant cell line of Shamouti orange (Citrus sinensis L. Osbeck). Embryogenesis was carried out both in the presence and absence of NaCl, yielding green and white globular embryos, respectively. Greening could be induced subsequently and normal heart shape embryo development was obtained. Plantlet formation required exposure to kinetin prior to the introduction of the root-inducing hormone naphthalene acetic acid. This system differs from the designed protocol for plant regeneration from the salt-sensitive, i.e., unselected callus. It is concluded that NaCl interferes with the regeneration process, with embryogenesis and/or embryo development into plantlets. Its presence during callus growth probably changes the balance of the phytohormones which is later manifested in plant regeneration. Citrus salt tolerant callus yields salt-tolerant embryos. Salt-tolerant calli derived from regenerated plantlets indicate acquisition of salt tolerance on the whole plant level. PMID- 24240462 TI - Embryogenic cell lines from somatic embryos of grape (Vitis vinifera L.). AB - Somatic embryo formation occurred on leaf callus of grape (Vitis vinifera cv. Koshusanjaku). An embryogenic callus was induced from somatic embryo clusters cultured on vitamin-, inositol- and glycine-free Nitsch and Nitsch (1969) medium supplemented with 1.0MUM 2,4-D. This callus has retained a high embryogenic activity after repeated subculture on the same medium for over two years, and has produced numerous embryos after transfer to a hormone-free medium. The effect of cytokinin treatment on somatic embryogenesis from leaf callus was also examined. N-(2-chloro-4-pyridyl)-N'-phenylurea (KT-30) and N-(1,2,3-thiadiazol-5-yl)-N' phenylurea (TAG), both synthetic cytokinins, were found to be effective for the induction of somatic embryogenesis. When leaf callus was induced by these cytokinins combined with 2,4-D at either 5.0 or 10.0MUM, somatic embryos were produced. PMID- 24240463 TI - Adventitious shoot regeneration from leaf tissue of three pear (Pyrus sp.) cultivars in vitro. AB - To develop an adventitious regeneration system for pear cultivars, several experiments were conducted with 2 cultivars of Pyrus communis L. ('Seckel' and 'Louise Bonne') and one cultivar of P. bretschneideri Rehd. ('Crystal Pear'). Half-leaves, taken from shoots proliferating on Lepoivre medium, were plated in petri-dishes on medium supplemented with various combinations of cytokinins and auxins. Cultures of the above cultivars had been established from mature trees. Among the growth regulators tested, thidiazuron (TDZ), combined with naphthalene acetic acid (NAA), was the most efficient for stimulation of adventitious shoots. The optimum level of TDZ was about 3 uM; shoot regeneration was observed over a wide range of TDZ and NAA concentrations (0.5 to 5 uM and 2.5 to 13 um, respectively). Among different macronutrient compositions, 1/2 and 1/4 Murashige and Skoog were the most effective. Sucrose concentrations (10 to 50 g L-1) had a linear significant effect on shoot regeneration of 'Crystal Pear'. PMID- 24240464 TI - Effect of age of cell suspension cultures on susceptibility to a fungal elicitor. AB - Fungal elicitor induced phytoalexin formation and the corresponding fluorescence transitions of the molecular probes pyranine and oxonol VI, in soybean (Glycine max Merr var Kent) and cotton (Gossypium arboreum L. Nanking) cell suspensions were both significantly affected by the age of the cells. During the lag phase and the beginning of the exponential growth phase both cultures exhibited stress responses (i.e. phytoalexin formation and molecular probe fluorescence transitions) in the absence of added elicitors. This behavior was termed autoelicitation because elicitation occurred without added external stimuli. In contrast, cells in the late exponential-early stationary phase were relatively unresponsive to elicitor. During intermediate growth periods the cell suspensions behaved optimally, producing no phytoalexins until stimulated with an elicitor. It would appear, therefore, that the culture period can be divided into 3 phases, with respect to susceptibility to fungal elicitors: a distinct autoelicitation period (immediately after transfer of the cells into fresh medium), followed by a period in which negligible amounts of phytoalexins are synthesized without elicitor, and culminating in a late period in which the cells respond poorly to elicitor. The onset and duration of these periods are somewhat different for soybean and cotton cells. PMID- 24240465 TI - Somatic embryogenesis and plant regeneration in diploid Allium fistulosum * A. cepa F1 hybrid onions. AB - Procedures were developed for disinfestation of non-dormant basal plate tissue excised from field grown basal plate tissue of diploid Allium fistulosum * A. cepa F1 hybrid onions. Contamination levels varied with the season and vegetative development of plant material. Callus initiated from basal plate tissue and immature inflorescences of the F1 hybrids was maintained on a BDS-based medium containing 0.75 mg/l picloram and 2.0 mg/l BA. When this medium was supplemented with vitamins and glycine, and with proline at 2.5 gm/1, somatic embryos began to form. Their development continued on a BDS-based shoot promotion medium containing 0.03 mg/l picloram and 0.32 mg/l 2iP supplemented with vitamins, glycine and proline. Genotypes differed significantly in the numbers of structures regenerated. Plantlets from somatic embryos were rooted into BDS or half-strength BDS medium without growth substances and were successfully transferred to sterilized potting mix in plastic commercial corsage boxes. PMID- 24240466 TI - Analysis of lipid composition and morphological characteristics in soybean regenerants. AB - A study was conducted to examine the extent of somaclonal variation of soybean plants, Glycine max (L.) Merrill cv. 'McCall', regenerated via somatic embryogenesis from cultured immature cotyledons using two different protocols. The sexual progeny of regenerants were compared with normal, seed-derived populations for morphological characteristics and fatty acid composition of seeds. First generation progeny of regenerants showed greater phenotypic variation than the control population, but this variation was not observed in the second generation. No stable somaclonal variants for fatty acid composition of the seed oil or morphological characteristics were observed, indicating that this somatic embryogenesis system should be adaptable for transformation with minimal generation of unwanted variation. PMID- 24240467 TI - PEG-mediated expression of GUS and CAT genes in protoplasts from embryogenic suspension cultures of Picea glauca. AB - beta-Glucuronidase (GUS) and chloramphenicol acetyl transferase (CAT) were used as reporter proteins in protoplasts from embryogenic suspension cultures of Picea glauca (Moench) Voss (white spruce). Plasmid DNA enclosing chimeric GUS and CAT constructs, using the cauliflower mosaic virus 35S promoter, was introduced into Picea glauca protoplasts using polyethylene glycol (PEG). Transient expression was detected 12 to 40 h after PEG-mediated DNA delivery. Dose-response curves using covalently closed circular plasmid DNA, in the absence of carrier DNA, have been obtained for each of these reporter genes. Linearized plasmid DNA gave lower levels of expression than covalently closed circular plasmid DNA when assayed 40 h after PEG-mediated DNA transfer. The use of carrier DNA (herring sperm DNA), in combination with covalently closed circular plasmid DNA, increased the level of expression of GUS by about 50%. CAT expression was enhanced if PEG-mediated delivery was performed on ice rather than at room temperature. The highest level of expression for CAT, and the lowest signal-to-noise ratio, was found 24 h after PEG-mediated DNA transfer. Both GUS and CAT provided results that were quantifiable and can therefore be used as reporter genes in Picea glauca. PMID- 24240468 TI - Plant regeneration from hypocotyl-derived protoplasts of Brassica juncea (L.) Czern and Coss. AB - Protoplasts isolated from etiolated hypocotyls of 6-day-old seedlings of Brassica juncea cv RLM 198 were cultured in a modified V47 medium containing 7% mannitol, 2% sucrose, 1.0 mg/l 2,4-D, 0.1 mg/l NAA and 0.4 mg/l BAP, at a density of 5*10(4) protoplasts per ml of medium. Cultures were incubated in the dark at 25+1 degrees C. After 7 d of culture, cell colonies were diluted with 8p medium containing 5% mannitol and a similar hormone combination as described earlier. After 14 d, cell colonies were embedded in 8p medium containing agarose and 3.5% mannitol. Immediately upon gelling, liquid 8p medium was added to each Petri dish as an overlayer, and cultures were incubated in the light. After a total of 3 to 4 weeks in culture, microcalli were obtained. A modified MS medium with 2% sucrose, 1.0 mg/l 2,4-D and 0.1 mg/l kinetin solidified with 0.5% agarose was used for growing microcalli into callus lines. On MS medium containing 2% sucrose, 0.1 mg/l IAA, 2.0 mg/l zeatin riboside and 2.0 mg/l BAP, solidified with 0.5% agarose, about 35% of the calli regenerated multiple shoots. The time required from culture of protoplasts to multiple shoot regeneration was about 10 weeks. Regenerated shoots were rooted and plants were re-established in a growth chamber at high frequency. PMID- 24240469 TI - Mitral valve and coronary artery bypass surgeries 13 years after pneumonectomy for lung cancer. AB - We successfully performed coronary artery bypass grafting and mitral valve replacement in a 72-year-old man who had undergone a left pneumonectomy 13 years previously due to a malignant mass. The patient was admitted to our clinic with symptoms of dyspnoea, palpitations, chest pain and fatigue. He was diagnosed with mitral valve disease and two-vessel coronary artery disease, as seen from echocardiography and catheterisation studies. Conventional cardiopulmonary bypass grafting was performed following sternotomy. The patient's heart was completely displaced to the left hemithorax. Saphenous vein grafts were harvested. Distal anastomoses were performed with the use of the on-pump beatingheart technique without cross clamping. Afterwards a cross clamping was placed and a left atriotomy was performed. The mitral valve was severely calcific. A mitral valve replacement was performed using number 27 mechanical valve after the valve had been excised. The patient's postoperative course was uneventful. Cardiac contractility was seen to be normal and the mitral valve was functioning on echocardiography done in the second postoperative month. PMID- 24240470 TI - Acute aortic dissection with a dangerous duo in an adolescent boy. AB - Acute type II aortic dissection and aortic coarctation are rare combined disorders. This report is of a patient with coarctation, a bicuspid aortic valve and type II dissection, who underwent emergency repair for the dissection, with aortic valve preservation. Repair of the coarctation was planned for a future occasion. The optimal sequence and timing of the repair, the best surgical technique, adequacy of blood perfusion, and the most appropriate arterial cannulation site are important issues in the repair of aortic dissection secondary to aortic coarctation. PMID- 24240471 TI - Wt1 in the kidney--a tale in mouse models. AB - The WT1 gene was originally identified through its involvement in the development of Wilms tumours. The gene is characterized by a plethora of different isoforms with, in some cases, clearly different functions in transcriptional control and RNA metabolism. Many different mouse models for Wt1 have already been generated, and these are increasingly providing new information on the molecular roles of Wt1 in normal development and disease. In this review we discuss the different models that have been generated and what they have taught us about the role of Wt1 in the kidney. PMID- 24240472 TI - Risk factors for early relapse during maintenance therapy after a single infusion of rituximab in children with steroid-dependent nephrotic syndrome. PMID- 24240473 TI - Fluoxetine epigenetically alters the CaMKIIalpha promoter in nucleus accumbens to regulate DeltaFosB binding and antidepressant effects. AB - Chronic social defeat stress in mice produces a susceptible phenotype characterized by several behavioral abnormalities consistent with human depression that are reversed by chronic but not acute exposure to antidepressant medications. Recent work in addiction models demonstrates that the transcription factor DeltaFosB and protein kinase calmodulin-dependent protein kinase II (CaMKII) are co-regulated in nucleus accumbens (NAc), a brain reward region implicated in both addiction and depression models including social defeat. Previous work has also demonstrated that DeltaFosB is induced in NAc after chronic social defeat stress or after chronic antidepressant treatment, wherein it mediates a pro-resilience or antidepressant-like phenotype. Here, using chromatin immunoprecipitation assays, we found that DeltaFosB binds the CaMKIIalpha gene promoter in NAc and that this binding increases after mice are exposed to chronic social defeat stress. Paradoxically, chronic exposure to the antidepressant fluoxetine reduces binding of DeltaFosB to the CaMKIIalpha promoter and reduces CaMKII expression in NAc, despite the fact that DeltaFosB is induced under these conditions. These data suggest a novel epigenetic mechanism of antidepressant action, whereby fluoxetine induces some chromatin change at the CaMKIIalpha promoter, which blocks the DeltaFosB binding. Indeed, chronic fluoxetine reduces acetylation and increases lysine-9 dimethylation of histone H3 at the CaMKIIalpha promoter in NAc, effects also seen in depressed humans exposed to antidepressants. Overexpression of CaMKII in NAc blocks fluoxetine's antidepressant effects in the chronic social defeat paradigm, whereas inhibition of CaMKII activity in NAc mimics fluoxetine exposure. These findings suggest that epigenetic suppression of CaMKIIalpha expression in NAc is behaviorally relevant and offer a novel pathway for possible therapeutic intervention in depression and related syndromes. PMID- 24240474 TI - LET dependence of the response of EBT2 films in proton dosimetry modeled as a bimolecular chemical reaction. AB - The dose response for films exposed to clinical x-ray beams is not linear and a calibration curve based on absorbed dose can be used to account for this effect. However for proton dosimetry the dose response of films exhibits an additional dependence because of the variation of the linear energy transfer (LET) as the protons penetrate matter. In the present study, we hypothesized that the dose response for EBT2 films can be mathematically described as a bimolecular chemical reaction. Furthermore, we have shown that the LET effect can be incorporated in the dose-response curve. A set of EBT2 films was exposed to pristine 161.6 MeV proton beams. The films were exposed to doses ranging from 0.93 to 14.82 Gy at a depth of 2 cm in water. The procedure was repeated with one film exposed to a lower energy beam (85.6 MeV). We also computed the LET and dose to water in the sensitive layer of the films with a validated Monte Carlo system, taking into account the film construction (polyester, adhesive and sensitive layers). The bimolecular model was able to accurately fit the experimental data with a correlation factor of 0.9998, and the LET correction factor was determined and incorporated into the dose-response function. We also concluded that the film orientation is important when determining the LET correction factor because of the asymmetric construction of the film. PMID- 24240475 TI - A network of epigenetic regulators guides developmental haematopoiesis in vivo. AB - The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo. PMID- 24240476 TI - Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. AB - Diseases affecting the kidney constitute a major health issue worldwide. Their incidence and poor prognosis affirm the urgent need for the development of new therapeutic strategies. Recently, differentiation of pluripotent cells to somatic lineages has emerged as a promising approach for disease modelling and cell transplantation. Unfortunately, differentiation of pluripotent cells into renal lineages has demonstrated limited success. Here we report on the differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells. The generated cells demonstrated rapid and specific expression of renal progenitor markers on 4-day exposure to defined media conditions. Further maturation into ureteric bud structures was accomplished on establishment of a three-dimensional culture system in which differentiated human cells assembled and integrated alongside murine cells for the formation of chimeric ureteric buds. Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic. PMID- 24240477 TI - The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis. AB - Dense multicilia in higher vertebrates are important for luminal flow and the removal of thick mucus. To generate hundreds of basal bodies for multiciliogenesis, specialized terminally differentiated epithelial cells undergo massive centriole amplification. In proliferating cells, however, centriole duplication occurs only once per cell cycle. How cells ensure proper regulation of centriole biogenesis in different contexts is poorly understood. We report that the centriole amplification is controlled by two duplicated genes, Cep63 and Deup1. Cep63 regulates mother-centriole-dependent centriole duplication. Deup1 governs deuterosome assembly to mediate large-scale de novo centriole biogenesis. Similarly to Cep63, Deup1 binds to Cep152 and then recruits Plk4 to activate centriole biogenesis. Phylogenetic analyses suggest that Deup1 diverged from Cep63 in a certain ancestor of lobe-finned fishes during vertebrate evolution and was subsequently adopted by tetrapods. Thus, the Cep63 gene duplication has enabled mother-centriole-independent assembly of the centriole duplication machinery to satisfy different requirements for centriole number. PMID- 24240478 TI - Combined effects of botulinum toxin injection and hind limb unloading on bone and muscle. AB - Bone receives mechanical stimulation from two primary sources, muscle contractions and external gravitational loading; but the relative contribution of each source to skeletal health is not fully understood. Understanding the most effective loading for maintaining bone health has important clinical implications for prescribing physical activity for the treatment or prevention of osteoporosis. Therefore, we investigated the relative effects of muscle paralysis and reduced gravitational loading on changes in muscle mass, bone mineral density, and microarchitecture. Adult female C57Bl/6J mice (n = 10/group) underwent one of the following: unilateral botulinum toxin (BTX) injection of the hind limb, hind limb unloading (HLU), both unilateral BTX injection and HLU, or no intervention. BTX and HLU each led to significant muscle and bone loss. The effect of BTX was diminished when combined with HLU, though generally the leg that received the combined intervention (HLU+BTX) had the most detrimental changes in bone and muscle. We found an indirect effect of BTX affecting the uninjected (contralateral) leg that led to significant decreases in bone mineral density and deficits in muscle mass and bone architecture relative to the untreated controls; the magnitude of this indirect BTX effect was comparable to the direct effect of BTX treatment and HLU. Thus, while it was difficult to definitively conclude whether muscle force or external gravitational loading contributes more to bone maintenance, it appears that BTX-induced muscle paralysis is more detrimental to muscle and bone than HLU. PMID- 24240480 TI - Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers. AB - BACKGROUND AND OBJECTIVES: Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), c.3435C>T (rs1045642)] and CYP3A5*3 (6986A>G) (rs776746) polymorphisms on the pharmacokinetics of quetiapine in humans. MATERIALS AND METHODS: Forty healthy male individuals were enrolled, and their ABCB1 and CYP3A5 polymorphisms were assessed. After a single dose of 100 mg quetiapine was administered, plasma concentrations of quetiapine were measured for 24 h and pharmacokinetic analysis was carried out. RESULTS: The ABCB1 polymorphisms including c.1236C>T, c.2677G>T/A, and c.3435C>>T did not affect plasma levels of quetiapine, and its pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the CYP3A5*3 polymorphism significantly affected the plasma level of quetiapine and its pharmacokinetics. The peak plasma concentration of quetiapine was 208.39 ng/ml for CYP3A5*1/*1, 243.46 ng/ml for CYP3A5*1/*3, and 332.94 ng/ml for CYP3A5*3/*3 (P=0.0118). The mean AUC(inf) (area under the time vs. concentration curve from 0 to infinity) value was 627.3, 712.77, and 1045.29 ng h/ml, respectively (P=0.0017). CONCLUSION: The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug. PMID- 24240479 TI - Cyclin-dependent kinase complexes in developing maize endosperm: evidence for differential expression and functional specialization. AB - Endosperm development in maize (Zea mays L.) and related cereals comprises a cell proliferation stage followed by a period of rapid growth coupled to endoreduplication. Regulation of the cell cycle in developing endosperm is poorly understood. We have characterized various subunits of cyclin-dependent kinase (CDK) complexes, master cell cycle regulators in all eukaryotes. A-, B-, and D type cyclins as well as A- and B-type cyclin-dependent kinases were characterized with respect to their RNA and protein expression profiles. Two main patterns were identified: one showing expression throughout endosperm development, and another characterized by a sharp down-regulation with the onset of endoreduplication. Cyclin CYCB1;3 and CYCD2;1 proteins were distributed in the cytoplasm and nucleus of cells throughout the endosperm, while cyclin CYCD5 protein was localized in the cytoplasm of peripheral cells. CDKB1;1 expression was strongly associated with cell proliferation. Expression and cyclin-binding patterns suggested that CDKA;1 and CDKA;3 are at least partially redundant. The kinase activity associated with the cyclin CYCA1 was highest during the mitotic stage of development, while that associated with CYCB1;3, CYCD2;1 and CYCD5 peaked at the mitosis-to-endoreduplication transition. A-, B- and D-type cyclins were more resistant to proteasome-dependent degradation in endoreduplicating than in mitotic endosperm extracts. These results indicated that endosperm development is characterized by differential expression and activity of specific cyclins and CDKs, and suggested that endoreduplication is associated with reduced cyclin proteolysis via the ubiquitin-proteasome pathway. PMID- 24240481 TI - Jan Evangelista Purkynje (1787-1869). PMID- 24240482 TI - Magnetic resonance imaging findings of developmental venous anomalies. AB - PURPOSE: This study evaluated morphological features of developmental venous anomalies (DVAs) based on magnetic resonance imaging (MRI) findings. The study also evaluated the factors affecting the visibility of DVAs on MRI. METHODS: We reviewed contrast-enhanced MRIs of 75 patients with DVA. The images were selected from 1,165 consecutive cranial MRIs. The images were examined for the DVA location, the number of collecting veins, the collecting vein diameter, drainage veins and sinuses, any accompanying parenchymal abnormalities or lesions, and the DVA visibility on MRI. RESULTS: DVAs prevalence was determined as 6.4 %. A total of 88 DVAs were observed. Single DVAs were observed in 65 patients, two were observed in 7 patients and three were observed in 3 patients. The DVA caputs had deep localization most frequently in 54.5 % of patients. A total of 98 collecting veins were identified, with a single vein identified in 80 DVAs. A statistically significant difference (p = 0.000) was found in the diameter of the collecting veins between DVAs that were the visible and nonvisible on noncontrast MRI. CONCLUSIONS: Most frequently, a single DVA was observed in the patients. A DVA caput could be located in the deep, subcortical, juxtacortical or deep + subcortical and juxtacortical + subcortical regions. Increasing collecting vein diameter increased visibility on noncontrast MRI, and small DVAs could be overlooked, even with contrast-enhanced MRI series if the images were not examined carefully. PMID- 24240483 TI - Hepatitis C virus nonstructural protein 5A favors upregulation of gluconeogenic and lipogenic gene expression leading towards insulin resistance: a metabolic syndrome. AB - Chronic hepatitis C is a lethal blood-borne infection often associated with a number of pathologies such as insulin resistance and other metabolic abnormalities. Insulin is a key hormone that regulates the expression of metabolic pathways and favors homeostasis. In this study, we demonstrated the molecular mechanism of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) induced metabolic dysregulation. We showed that transient expression of HCV NS5A in human hepatoma cells increased lipid droplet formation through enhanced lipogenesis. We also showed increased transcriptional expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha and diacylglycerol acyltransferase-1 (DGAT-1) in NS5A-expressing cells. On the other hand, there was significantly reduced transcriptional expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferator-activated receptor gamma (PPARgamma) in cells expressing HCV NS5A. Furthermore, increased gluconeogenic gene expression was observed in HCV-NS5A-expressing cells. In addition, it was also shown that HCV-NS5A-expressing hepatoma cells show serine phosphorylation of IRS-1, thereby hampering metabolic activity and contributing to insulin resistance. Therefore, this study reveals that HCV NS5A is involved in enhanced gluconeogenic and lipogenic gene expression, which triggers metabolic abnormality and impairs insulin signaling pathway. PMID- 24240484 TI - Comparison of minimally invasive versus open transforaminal lumbar interbody fusion in two-level degenerative lumbar disease. AB - PURPOSE: The purpose of this study was to compare the clinical and radiological outcomes of minimally invasive versus open transforaminal lumbar interbody fusion in two-level degenerative lumbar disease. METHODS: We conducted a prospective cohort study of 82 patients, who underwent two-level minimally invasive or open transforaminal lumbar interbody fusion (TLIF) from March 2010 to December 2011. Forty-four patients underwent minimally invasive transforaminal lumbar interbody fusion (MITLIF) (group A) and 38 patients underwent the traditional open TLIF (group B). Demographic data and clinical characteristics were comparable between the two groups before surgery (p > 0.05). Peri-operative data, clinical and radiological outcomes between the two groups were compared. RESULTS: The mean follow-up period was 20.6 +/- 4.5 months for group A and 20.0 +/- 3.3 months for group B (p > 0.05). No significant difference existed in operating time between the two group (p > 0.05). X-ray exposure time was significantly longer for MITLIF compared to open cases. Intra-operative blood loss and duration of postoperatively hospital stay of group A were significantly superior to those of group B (p < 0.05). On postoperative day three, MITLIF patients had significantly less pain compared to patients with the open procedure. No statistical difference existed in pre-operative and latest VAS value of back pain (VAS-BP) and leg pain (VAS-LP), pre-operative and latest ODI between the two groups. The fusion rate of the two groups was similar (p < 0.05). Complications included small dural tear, superficial wound infection and overlong screws. When comparing the total complications, no significant difference existed between the groups (p > 0.05). CONCLUSIONS: MITLIF offers several potential advantages including postoperative back pain and leg pain, intra-operative blood loss, transfusion and duration of hospital stay postoperatively in treating two-level lumbar degenerative disease. However, it required much more radiation exposure. PMID- 24240485 TI - Comparative study of ranibizumab and bevacizumab on corneal neovascularization in rabbits. AB - PURPOSE: The aim was to compare the effect of subconjunctival injections of ranibizumab and bevacizumab on corneal neovascularization (NV) in rabbits. METHODS: NV was induced by placing a suture at the corneal periphery of rabbits (n = 30 eyes). Immediately after suturing, the rabbits were divided into 3 groups and 7 days later administered subconjunctival injections of ranibizumab (Lucentis; 0.5 mg/0.05 mL), bevacizumab (Avastin; 5 mg/0.05 mL), or normal saline (control), respectively. The time-course photographs to measure the area of the corneal NV were obtained on days 7, 10, and 14 after suture placement. Histological examination and immunohistochemical analysis for the vascular endothelial growth factor and CD34 were performed. RESULTS: Analysis of digital photographs showed that there was less corneal NV in the ranibizumab- and bevacizumab-treated eyes than in the control eyes (P = 0.012, 1-way analysis of variance); however, no significant differences between the ranibizumab- and bevacizumab-treated eyes were seen. In addition, there was less staining for vascular endothelial growth factor and CD34 in the corneas from the ranibizumab treated eyes and bevacizumab-treated eyes than in the control eyes, and there were no significant differences in the staining intensity between the ranibizumab and bevacizumab-treated eyes. Subconjunctival ranibizumab and bevacizumab injections were not associated with any complications during observations. CONCLUSIONS: Subconjunctival administrations of ranibizumab or bevacizumab inhibit corneal NV in rabbits and have equivalent effects on it. PMID- 24240486 TI - Peripheral ulcerative keratitis and corneal melt: a 10-year single center review with historical comparison. AB - PURPOSE: Management of noninfectious ulcerative keratitis (UK) and associated systemic disorders has changed over recent years. This study aimed to analyze a recent cohort of patients with UK in this context. METHODS: The case notes of all the patients attending a specialist corneal immunosuppression clinic between June 2002 and July 2012 were reviewed. A subgroup comparison of those with rheumatoid arthritis (RA) was made with those included in an earlier report from this same center (Malik et al. Eur J Ophthalmol. 2006;16:791-797). The Fisher exact test was used for statistical comparison, and a Bonferroni correction was applied. RESULTS: Seventy patients, whose mean age was 65.0 years (median, 64 years), were included. Fifteen (21%) had bilateral disease, and forty-six had RA (66%). At presentation, the mean (median) visual acuity (VA) was 0.59 (0.18) logarithm of the minimum angle of resolution equivalent to 6/24 (6/9) Snellen. All the patients were prescribed systemic corticosteroids, which were later stopped in 45 (64%) patients. All but 2 were treated with steroid-sparing immunosuppressive agents, with each patient being prescribed a mean of 1.5 medications (range, 0 4), including prednisolone. These included prednisolone (70, 100%), methotrexate (47, 67%), mycophenolate (15, 21%), tacrolimus (5, 7%), and azathioprine (4, 6%). No irreversible side effects occurred. After perforation, 12 eyes of 11 patients (16%) underwent a corneal transplantation, and 10 (83%) of these remained clear. The mean (median) VA of the affected eyes when last seen was 0.34 (0.18) logarithm of the minimum angle of resolution equivalent to 6/13 (6/9) Snellen. The subset of patients with RA had significantly lower rates of corneal perforation and a VA <= 6/60 when last seen (P < 0.05) compared with that of the earlier cohort. CONCLUSIONS: Ocular morbidity associated with UK has fallen, possibly because of a move toward more aggressive systemic antiinflammatory therapy. PMID- 24240487 TI - Vernal keratoconjunctivitis with giant papillae on the inferior tarsal conjunctiva. AB - PURPOSE: In vernal keratoconjunctivitis (VKC), giant papillae are commonly observed on the superior tarsal conjunctiva. We found 3 cases of giant papillae on the inferior tarsal conjunctiva, and diagnosed them as being VKC based on their clinical and histopathological features. METHODS: Three patients with inferior tarsal giant papillae were studied. In 2 patients, the giant papillae were resected for therapeutic purposes. Immunohistochemical analysis was carried out by indirect immunofluorescent staining using anti-CD3, anti-CD20, anti-CD35 antibodies. RESULTS: In all 3 patients, giant papilla formation was observed on the inferior lid margin. Clusters of CD20 B lymphocytes with CD35 follicular dendritic cells, and CD3 marginal zone T lymphocytes, common features of lymphoid neogenesis, were observed. In 2 patients, typical giant papillary formation was also observed on the superior tarsal conjunctiva. In all the patients, topical dexamethasone and tacrolimus treatments were found to be effective. CONCLUSIONS: The giant papillae of VKC can occur not only on the superior tarsal conjunctiva but also on the inferior tarsal conjunctiva. The possibility of the presence of giant papillae on the inferior tarsal conjunctiva should be considered in the clinical examination of patients with VKC. PMID- 24240489 TI - Corneal collagen fibril changes after ultraviolet a/riboflavin corneal crosslinking. AB - PURPOSE: The aim was to investigate the changes in collagen type 1 and type 3 in rabbit corneas undergoing corneal crosslinking with ultraviolet A and riboflavin and to analyze the possible mechanisms of corneal haze formation. METHODS: After removal of the central epithelium, the right corneas of 60 New Zealand rabbits were crosslinked with riboflavin and ultraviolet A, and 10 additional rabbits were used as the control group. The animals were killed 3, 7, 15, 30, 90, and 180 days postoperatively. Collagen type 1 and type 3 were analyzed using picrosirius red stain by means of polarized light microscopy. The biochemical changes in collagen type 3 at the time points indicated above were determined by Western blot analyses. RESULTS: Collagen type 3 was significantly increased 30 days after corneal crosslinking compared with that in the control cornea, gradually increased until reaching its maximum value 90 days after riboflavin and ultraviolet A crosslinking, and then decreased until it returned to the normal state 180 days after crosslinking. There were no significant changes in collagen type 1 over time after corneal crosslinking. In agreement with the picrosirius red staining results, the western blot analyses showed that collagen type 3 was detected 15 days after the crosslinking treatment and continued to be present. However, 180 days after the crosslinking treatment, collagen type 3 could not be found in the crosslinked corneas. CONCLUSIONS: These findings suggest that ultraviolet A/riboflavin crosslinking results in collagen type 3 synthesis and degradation, which may offer at least a partial explanation for the formation of corneal haze. PMID- 24240488 TI - Descemet stripping endothelial keratoplasty for the treatment of combined fuchs corneal endothelial dystrophy and keratoconus. AB - PURPOSE: To report the first case series of patients with Fuchs corneal endothelial dystrophy (FCD) and keratoconus (KCN) who underwent Descemet stripping endothelial keratoplasty (DSEK). METHODS: This is a retrospective case series of 6 eyes of 4 patients with combined FCD and KCN who underwent DSEK at 3 different centers. Clinical information collected included corneal topography measurements, central corneal thickness, and endothelial cell count. Visual outcomes and change in keratometric measurements were evaluated. RESULTS: The follow-up for patients ranged from 10 to 72 months. The best-corrected visual acuity was 20/40 or better in all 6 eyes. The mean keratometric measurements decreased in all cases (range of 0.5-5.8 diopters); however, topography still demonstrated an inferior steepening in each case. CONCLUSIONS: Patients with FCD and KCN have been previously reported as being managed with penetrating keratoplasty. We present 6 eyes of 4 patients who were managed with DSEK for the FCD. Topographically, the characteristic inferior steepening of KCN did not change; however, all patients with DSEK had flatter postoperative keratometric measurements with improved visual acuity. If a DSEK is performed for FCD before apical corneal scarring from KCN, a good visual outcome may be achieved. PMID- 24240490 TI - Clinical outcomes of corneal graft infections caused by multi-drug resistant Pseudomonas aeruginosa. AB - PURPOSE: The aim was to assess the clinical outcomes of corneal graft infections caused by multi-drug resistant Pseudomonas aeruginosa (MDR-PA). METHODS: This is a retrospective case series of 38 patients with corneal graft infections caused by MDR-PA managed from June to December 2011. Clinical and demographic details, treatment outcome on primary therapy, cases requiring a repeat graft, their outcome, and recurrence rate on treatment were analyzed. The outcome measure was resolution of infection. Success was "complete" if resolution was seen without subsequent recurrence up to 2 weeks and "partial" if it required intervention such as cyanoacrylate glue application. It was a "failure" if the infection could not be controlled and the patient required a repeat graft or the eye had to be eviscerated. RESULTS: Thirty-one patients were initially treated with topical cefazolin 5% and ciprofloxacin 0.3%, 6 with topical colistin 0.19%, and 1 was treated with topical imipenem 1%. On this treatment, 9 cases showed complete success and 6 showed partial success. Twenty-two patients required a repeat graft, and 1 eye was eviscerated. The patients with outcome of success had smaller graft infiltrates (median area = 2 mm; range = 1-24.6 mm vs. median infiltrate area = 24.8 mm; range = 1.5-64 mm) than those with an outcome of failure (P = 0.02). At the mean follow-up of 50 days, recurrence after the repeat surgery was seen in 4/22 (18.2%) patients. CONCLUSIONS: Medical therapy can be tried in sensitive and smaller MDR-PA graft infiltrates, but larger infiltrates and those with endophthalmitis require early surgical intervention. PMID- 24240491 TI - Restoration of human lacrimal function following platelet-rich plasma injection. AB - PURPOSE: The aim was to evaluate the effect of autologous platelet-rich plasma on lacrimal function in patients with severe dry eye. METHODS: A prospective interventional case series design was adopted. Four patients with severe lacrimal dysfunction and severe dry eye were treated. Platelet rich-activated plasma (1 mL) was injected adjacent to the lacrimal gland on day 0 and at 4, 8, and 12 weeks. The objective parameters included a Schirmer test, ocular surface staining, and tear break-up time (TBUT). The patients were followed up for 12 weeks after the first injection. RESULTS: All cases showed a significant improvement in lacrimal volume (from 3.3 +/- 0.8 mm to 11.1 +/- 2.3 mm). In all the patients, an increase in tear break-up time values and a decrease in ocular staining (basal 8.0 +/- 0.61-2.8 +/- 0.5) with subjective improvement occurred. None of the patients presented any adverse effect, and none reported pain or discomfort. Additionally, no complications were observed. CONCLUSIONS: Injected platelet-enriched plasma was found to be safe and effective in increasing lacrimal production and in improving ocular staining secondary to severe dry eye. This approach could be an alternative for the management of these patients, although additional studies are required to perfect the technique. PMID- 24240492 TI - [The German Journal for Child and Adolescent Psychiatry and Psychotherapy on its own behalf - current developments and future perspectives]. PMID- 24240493 TI - [An international neuropsychological assessment tool for children, adolescents, and adults with anorexia nervosa - the German adaptation of the Ravello Profile]. AB - OBJECTIVE: Adults with anorexia nervosa (AN) show weaknesses in several cognitive functions before and after weight restoration. There is a great demand for standardized examinations of executive functioning in the field of child and adolescent AN. Previous studies exhibited methodological inconsistencies regarding test selection and operationalization of cognitive functions, making the interpretation of their findings difficult. In order to overcome these inconsistencies, a neuropsychological assessment tool, the "Ravello Profile," was developed, though previously not available in German. This paper presents a German adaptation of the Ravello Profile and illustrates its applicability in children and adolescents via three case descriptions. METHODS: The Ravello Profile was adapted for the German-speaking area. The applicability of the Ravello Profile was evaluated in three children and adolescents with AN. RESULTS AND CONCLUSIONS: The cases presented confirm the feasible implementation of this adaptation of the Ravello Profile, both in children and adolescents. Hence, it enables a methodologically consistent examination of executive functioning in German-speaking children, adolescents, and adults with AN. Using the Ravello Profile, the role of cognitive functions in the development of AN can be systematically examined over a broad age range. PMID- 24240494 TI - [Stress symptoms and stress coping in depressed girls]. AB - OBJECTIVE: Depressive disorders occur frequently in adolescents. Maintenance of depression has been related to stress and stress coping. METHOD: The study describes which stress load and which strategies of stress coping are present in girls with major depression. 74 girls with major depression were compared to a normal control group with regard to stress symptoms and stress coping. All subjects were diagnosed with a structured clinical interview according to DSM-IV criteria. Stress and stress coping strategies were measured by standardized and validated questionnaires. RESULTS: Girls with major depression had more symptoms of stress and were characterized by inadequate stress coping compared to the control group. CONCLUSION: These cross-sectional data show deficits in stress coping that might reinforce stress symptoms as well as degree of depression. However, cause and effect can only be clarified by a longitudinal design. PMID- 24240496 TI - Gender differences in methods of suicide attempts and prevalence of previous suicide attempts. AB - OBJECTIVE: Suicide attempts are important predictors of completed suicide. Adolescents admitted to the emergency room of a large university hospital in Bern after a suicide attempt during the years 2004-2010 were prospectively assessed for methods of suicide attempt. METHOD: Adolescents (N = 257; 66.5% female; age 14-21 years), presenting after a suicide attempt, were assessed with the WHO/EURO Multicentre Study on Parasuicide assessment tool. RESULTS: Males more often used jumping from a high place (14% vs. 4.6% in females, p < .05) and less often intoxication (36% vs. 71.3%, p < .01). At least one previous suicide attempt was reported in 100 patients (44.4%; more females than males: Cramer-V = 0.21; p = .002). Of these, 35 adolescents did not present to this hospital or not at all for a previous suicide attempt. CONCLUSIONS: The present study is the first to examine methods of suicide attempts according to the ICD-10 X codes in this age group. Gender differences were observed. Because a relevant number of patients did not present to the same hospital or not at all for a previous suicide attempt, studies on pathways to care of adolescents after their first suicide attempt are important for early detection and intervention strategies. PMID- 24240495 TI - Severe affective and behavioral dysregulation in youths is associated with a proinflammatory state. AB - OBJECTIVE: A heritable behavioral phenotype, the so-called Dysregulation Profile (DP), characterized by extreme scores on the syndrome scales Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AGG), has been identified on the Child Behavior Checklist (CBCL). It characterizes children with severe affective and behavioral dysregulation. The present study examined possible alterations of the inflammatory system in CBCL-DP using a clinical sample of n = 133 children and adolescents. METHOD: Participants with the CBCL-DP scoring >= 2.5 SDs above average constituted the CBCL-DP subgroup (n = 51). Those with CBCL-DP scores of 1 SD or less above average were regarded as controls (n = 82). Groups were compared in terms of serum levels of C-reactive protein (CRP) and albumin. RESULTS: Participants showing the CBCL-DP exhibited increased CRP and decreased albumin levels compared to controls. CRP was correlated with AGG, AP, and the CBCL-DP total score. A negative correlation was observed between albumin and AGG, AP, the CBCL-DP score, and A/D. These associations could not be attributed to differences in age, sex, weight, socioeconomic status, global functioning, or duration of illness. CONCLUSIONS: This is the first study to demonstrate associations between the CBCL-DP and a proinflammatory state. Limitations include the lack of a healthy control group, the use of a single measurement of inflammatory markers, and the lack of follow-up data. Future research should address whether inflammatory diathesis in these children confers increased susceptibility to later development of cardiovascular disease and other medical morbidities. PMID- 24240497 TI - [Adolescent parenting - developmental risks for the mother-child dyad]. AB - Adolescent mothers and their children are exposed to multiple psychosocial risk factors and represent a high-risk group for adverse developmental outcomes. It is not the mother's young age alone which contributes to the developmental risk of the mother-child dyad. Rather, both the combination of risks, such as poverty, domestic violence, dysfunctional family relationships, or a psychiatric disorder, all of which predispose to adolescent pregnancy, as well as the strains of parenthood during the mother's own developmental stage add to the psychosocial risks of children of teenage mothers. Early motherhood can lead to lower levels of education and a lower socioeconomic status. In addition, there is a higher risk for psychopathology in both the teenage mother and her child. This article provides an overview of the current research findings regarding adolescent parenting and its associated risks. Risk factors leading to early motherhood are reviewed and associated with differences in parenting behaviors and the developmental outcomes of their children. This article will conclude with a short overview on intervention programs for adolescent mothers and their children. Further research is needed to develop age-appropriate support programs for adolescent mothers and their children to cope with the complexity of risks and improve their developmental trajectories. PMID- 24240498 TI - [What happens to children and adolescents with mental disorders? Findings from long-term outcome research]. AB - Research on the long-term outcome of mental disorders originating in childhood and adolescence is an important part of developmental psychopathology. After a brief sketch of relevant terms of outcome research, the first part of this review reports findings based on heterotypic cohort studies. The major second part of this review presents findings based on long-term outcome studies dealing with homotypic diagnostic groups. In particular, the review focuses on the course and prognosis of ADHD, anxiety disorders, depression, conduct disorders, eating disorders, autism spectrum disorders, schizophrenia, and selective mutism. Findings mainly support the vulnerability hypothesis regarding mental disorders with early manifestation in childhood and adolescence as frequent precursors of mental disorders in adulthood. The discussion focuses on the impact of early manifesting disorders in the frame of general mental morbidity and of the effect of interventions, which is not yet sufficiently discernible. PMID- 24240499 TI - Clinical problems encountered in the treatment of adolescents with anorexia nervosa. AB - The conceptualization of anorexia nervosa (AN) depends on the diagnostic criteria. Most patients with teenage onset AN seem to remit within 3-10 years depending on the definitions of recovery. The mortality of adolescent onset anorexia nervosa (AN) has fortunately decreased over the last two decades. Based on randomized controlled trials, we review different treatments including individual and group psychotherapy, family therapy, psychopharmacology, and hormone therapy. Treatment settings vary over time for any individual patient. Despite high rates of inpatient treatment, the respective evidence for effectiveness is meager. In underage patients with severe AN clinical, ethical and legal aspects need to be dealt with systematically if intermittent compulsory treatment is deemed necessary. The prolonged and frequently chronic course of AN often entails therapeutic discontinuity; the transition into adulthood requires a graded therapeutic concept that considers the severity of the disorder, developmental and chronological age, and parental involvement. Finally, we consider future clinical and research options to improve treatment and outcome of this eating disorder. PMID- 24240500 TI - [Magnetic resonance imaging (MRI) in children and adolescents - study design of a feasibility study concerning examination related emotions]. AB - Numerous research centres apply magnetic resonance imaging (MRI) for research purposes in children. In view of this practical research, ethical concerns regarding the strains the study participants are exposed to during the MRI examination are discussed. The study evaluates whether an MRI examination induces negative emotions in children and adolescents which are more intense than the ones caused by electroencephalography (EEG), an examination method currently classified as causing "minimal stress." Furthermore, the emotional stress induced by the MRI examination in children and adolescents is compared with that induced in adults. The study gathers data on examination-related emotions in children (age 8-17;11, male and female) who undergo an MRI examination of the cerebrum with a medical indication. The comparison group is a sample of children and adolescents examined with EEG (age 8-17;11, male and female) as well as a sample of adults (age 18-65, male and female) examined with MRI. At present, the study is in the stage of data collection. This article presents the study design of the MRI research project. PMID- 24240504 TI - Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer. AB - PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy +/- 7.93 and 17.14 +/- 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 +/- 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 +/- 0.46 and 1.68 +/- 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 +/- 4.21 and 15.76 +/- 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3). PMID- 24240505 TI - Metabolism: digging up enzyme functions. PMID- 24240506 TI - Direct evidence for a covalent ene adduct intermediate in NAD(P)H-dependent enzymes. AB - The pyridine nucleotides NADH and NADPH (NAD(P)H) are ubiquitous redox coenzymes that are present in all living cells. Although about 16% of all characterized enzymes use pyridine nucleotides as hydride donors or acceptors during catalysis, a detailed understanding of how the hydride is transferred between NAD(P)H and the corresponding substrate is lacking for many enzymes. Here we present evidence for a new mechanism that operates during enzymatic hydride transfers using crotonyl-CoA carboxylase/reductase (Ccr) as a case study. We observed a covalent ene intermediate between NADPH and the substrate, crotonyl-CoA, using NMR, high resolution MS and stopped-flow spectroscopy. Preparation of the ene intermediate further allowed direct access to the catalytic cycle of other NADPH-dependent enzymes-including those from type II fatty acid biosynthesis-in an unprecedented way, suggesting that formation of NAD(P)H ene intermediates is a more general principle in catalysis. PMID- 24240507 TI - A widespread self-cleaving ribozyme class is revealed by bioinformatics. AB - Ribozymes are noncoding RNAs that promote chemical transformations with rate enhancements approaching those of protein enzymes. Although ribozymes are likely to have been abundant during the RNA world era, only ten classes are known to exist among contemporary organisms. We report the discovery and analysis of an additional self-cleaving ribozyme class, called twister, which is present in many species of bacteria and eukarya. Nearly 2,700 twister ribozymes were identified that conform to a secondary structure consensus that is small yet complex, with three stems conjoined by internal and terminal loops. Two pseudoknots provide tertiary structure contacts that are critical for catalytic activity. The twister ribozyme motif provides another example of a natural RNA catalyst and calls attention to the potentially varied biological roles of this and other classes of widely distributed self-cleaving RNAs. PMID- 24240508 TI - Revealing the hidden functional diversity of an enzyme family. AB - Millions of protein database entries are not assigned reliable functions, preventing the full understanding of chemical diversity in living organisms. Here, we describe an integrated strategy for the discovery of various enzymatic activities catalyzed within protein families of unknown or little known function. This approach relies on the definition of a generic reaction conserved within the family, high-throughput enzymatic screening on representatives, structural and modeling investigations and analysis of genomic and metabolic context. As a proof of principle, we investigated the DUF849 Pfam family and unearthed 14 potential new enzymatic activities, leading to the designation of these proteins as beta keto acid cleavage enzymes. We propose an in vivo role for four enzymatic activities and suggest key residues for guiding further functional annotation. Our results show that the functional diversity within a family may be largely underestimated. The extension of this strategy to other families will improve our knowledge of the enzymatic landscape. PMID- 24240509 TI - Tolvaptan therapy for massive edema in a patient with nephrotic syndrome. AB - BACKGROUND: Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema. The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS. CASE DIAGNOSIS/TREATMENT: We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist. CONCLUSIONS: Tolvaptan is effective for the treatment of massive edema caused by NS. Larger studies are needed in the future to fully assess the value and safety of tolvaptan use for this condition. PMID- 24240510 TI - Automatic extraction of pectoral muscle in the MLO view of mammograms. AB - A mammogram is the standard modality used for breast cancer screening. Computer aided detection (CAD) approaches are helpful for improving breast cancer detection rates when applied to mammograms. However, automated analysis of a mammogram often leads to inaccurate results in the presence of the pectoral muscle. Therefore, it is necessary to first handle pectoral muscle segmentation separately before any further analysis of a mammogram. One difficulty to overcome when segmenting out pectoral muscle is its strong overlapping with dense glandular tissue which tampers with its extraction. This paper introduces an automated two-step approach for pectoral muscle extraction. The pectoral region is firstly estimated through segmentation by mean of a modified Fuzzy C-Means clustering algorithm. After contour validation, the final boundary is delineated through iterative refinement of edge point using average gradient. The proposed method is quite simple in implementation and yields accurate results. It was tested on a set of images from the MIAS database and yielded results which, compared to those of some state-of-the-art approaches, were better. PMID- 24240511 TI - Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients- nonlinear mixed effects modelling approach. AB - PURPOSE: The purpose of the study was to examine and describe adjunctive lamotrigine (LTG) pharmacokinetics in paediatric and young adult patients using a nonlinear mixed effects modelling (NONMEM) approach. METHODS: The study included 53 patients (age range 3-35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools. RESULTS: The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: <=25 kg, >25 to <60 kg and >=60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing <=25 kg, >25 to <60 kg or >=60 kg who was concomitantly treated with CBZ was estimated to be 3.28, 4.23, or 7.15 l/h, respectively. If a patient was concomitantly treated with CBZ + VPA, the CL/F decreased on average by 69.5 % relative to LTG + CBZ co-therapy. VPA was found to decrease the LTG CL/F by 87.6 % compared to co-therapy with only CBZ. CONCLUSION: The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring. PMID- 24240512 TI - Intraoperative optical imaging and tissue interrogation during urologic surgery. AB - PURPOSE OF REVIEW: To review optical imaging technologies in urologic surgery aimed to facilitate intraoperative imaging and tissue interrogation. RECENT FINDINGS: Emerging new optical imaging technologies can be integrated in the operating room environment during minimally invasive and open surgery. These technologies include macroscopic fluorescence imaging that provides contrast enhancement between normal and diseased tissue and microscopic imaging that provides tissue characterization. SUMMARY: Optical imaging technologies that have reached the clinical arena in urologic surgery were reviewed, including photodynamic diagnosis, near infrared fluorescence imaging, optical coherence tomography, and confocal laser endomicroscopy. PMID- 24240514 TI - A commentary on Pitfalls of predicting complex traits from SNPs. PMID- 24240513 TI - Evolution of crop species: genetics of domestication and diversification. AB - Domestication is a good model for the study of evolutionary processes because of the recent evolution of crop species (<12,000 years ago), the key role of selection in their origins, and good archaeological and historical data on their spread and diversification. Recent studies, such as quantitative trait locus mapping, genome-wide association studies and whole-genome resequencing studies, have identified genes that are associated with the initial domestication and subsequent diversification of crops. Together, these studies reveal the functions of genes that are involved in the evolution of crops that are under domestication, the types of mutations that occur during this process and the parallelism of mutations that occur in the same pathways and proteins, as well as the selective forces that are acting on these mutations and that are associated with geographical adaptation of crop species. PMID- 24240515 TI - Author reply to A commentary on Pitfalls of predicting complex traits from SNPs. PMID- 24240516 TI - GTPase Ran strongly accumulates at the kinetochores of somatic chromosomes in the spermatogonial mitoses of Acricotopus lucidus (Diptera, Chironomidae). AB - Unequal chromosome segregation and spindle formation occurs in the last gonial mitosis in the germ line of the chironomid Acricotopus lucidus. During this differential mitosis, all germ line-limited chromosomes (=Ks) migrate undivided to only one pole of the cell, while the somatic chromosomes (=Ss) first remain in the metaphase plane, and with the arrival of the Ks at the pole, they then separate equally. The evolutionarily conserved GTPase Ran plays a crucial role in many cellular processes. This includes the regulation of microtubule nucleation and stabilisation at kinetochores and of spindle assembly during mitosis, which is promoted by a RanGTP concentration gradient that forms around the mitotic chromosomes (Kalab et al. in Science 295:2452-2456, 2002, Nature 440:697-701, 2006). In the present study, a strong accumulation of Ran was detected by immunofluorescence at the kinetochores of the Ss in normal gonial and differential gonial mitoses of males of A. lucidus. In contrast, no Ran accumulation was observed at the kinetochores of the Ss in the metaphases of brain ganglia mitoses or of aberrant spermatocytes or in metaphases I and II of spermatocyte meiotic divisions. Likewise, there was no accumulation at the kinetochores of Drosophila melanogaster mitotic chromosomes from larval brains. The specific accumulation of Ran at the kinetochores of the Ss in differential gonial mitoses of A. lucidus strongly suggests that Ran is involved in a mechanism acting in this exceptional mitosis, which retains the Ss at the metaphase plane and prevents a premature separation and unequal segregation of the Ss during monopolar migration of the Ks. PMID- 24240517 TI - Development of cycad ovules and seeds. 2. Histological and ultrastructural aspects of ontogeny of the embryo in Encephalartos natalensis (Zamiaceae). AB - Development of the embryo of Encephalartos natalensis from a rudimentary meristematic structure approximately 700 MUm in length extends over 6 months after the seed is shed from the strobilus. Throughout its development, the embryo remains attached to a long suspensor. Differentiation of the shoot meristem flanked by two cotyledonary protuberances occurs over the first 2 months, during which peripheral tannin channels become apparent. Tannins, apparently elaborated by the endoplasmic reticulum, first accumulate in the large central vacuole and ultimately fill the channel. By the fourth month of development, the root meristem is apparent and procambial tissue forming discrete vascular bundles can be discerned in the elongating cotyledons. Between 4 and 6 months, mucilage ducts differentiate; after 6 months, when the seed becomes germinable, the embryo is characterised by cotyledons far longer than the axis. Shoot and root meristem cells remain ultrastructurally similar throughout embryo ontogeny, containing small vacuoles, many well-differentiated mitochondria and endoplasmic reticulum (ER) profiles, abundant polysomes, plastids containing small starch deposits and Golgi bodies. Unusually, however, Golgi bodies are infrequent in other cells including those elaborating mucilage which is accumulated in distended ER and apparently secreted into the duct lumen directly by ER-derived vesicles. The non meristematic cells accumulate massive starch deposits to the exclusion of any protein bodies and only very sparse lipid, features which are considered in terms of the prolonged period of embryo development and the high atmospheric oxygen content of the Carboniferous Period, when cycads are suggested to have originated. PMID- 24240518 TI - A novel transcription factor JcNAC1 response to stress in new model woody plant Jatropha curcas. AB - Jatropha curcas, a biodiesel plant with a short life cycle, has great potentials to be a new model woody plant. In this study, we found a plant-specific transcription factor JcNAC1, an intriguing regulator modulating plant responses to abiotic stresses and pathogen infection. Expression of JcNAC1 was strongly increased when plants were treated with abscisic acid, salt and polyethylene glycol, and was decreased with salicylic acid, ethylene, and pathogens. Overexpressing JcNAC1 plants showed enhanced tolerance to drought and increased susceptibility to pathogens. Furthermore, over-expression of JcNAC1 in plants also resulted in the expression changes of some stress-related maker genes including curcin-L, which is a special stress-inducible ribosome-inactivating protein gene in J. curcas. These results indicate that JcNAC1 is responsible for stress responses in J. curcas. PMID- 24240519 TI - The value of computed tomography based navigation in revision total hip arthroplasty. AB - PURPOSE: This study investigates the accuracy of a computed tomography (CT)-based navigation system for accurate acetabular component placement during revision total hip arthroplasty (THA). METHODS: We performed a retrospective review of 30 hips in 26 patients who underwent cementless revision THA using a CT-based navigation system; the control group consisted of 25 hips in 25 patients who underwent cementless primary THA using the same system. We analysed the deviation of anteversion and inclination angles among the pre-operative plan, intra operative records from the navigation system and data from postoperative CT scans. RESULTS: There were no significant differences between groups (P < 0.05) in terms of mean deviation between pre-operative planning and postoperative measurements or between intraoperative records and postoperative measurements. CONCLUSION: CT-based navigation in revision THA is a useful tool that enables the surgeon to implant the acetabular component at the precise angle determined in pre-operative planning. PMID- 24240521 TI - [Vascular functional alterations in hypertrophic cardiomyopathy]. AB - Hypertrophic cardiomyopathy is a hereditary, not uncommon cardiac disease, which is associated with asymmetric thickening and hypertrophy of the interventricular septum unrelated to hemodynamic reasons. Despite hypertrophic cardiomyopathy is considered to be a disorder of the heart muscle, several associated vascular alterations have been described. The aim of the present review is to summarize vascular functional alterations in hypertrophic cardiomyopathy. PMID- 24240520 TI - The ventricular system of the brain: a comprehensive review of its history, anatomy, histology, embryology, and surgical considerations. AB - INTRODUCTION: The cerebral ventricles have been recognized since ancient medical history. Their true function started to be realized more than a thousand years later. Their anatomy and function are extremely important in the neurosurgical panorama. METHODS: The literature was searched for articles and textbooks of different topics related to the history, anatomy, physiology, histology, embryology and surgical considerations of the brain ventricles. CONCLUSION: Herein, we summarize the literature about the cerebral ventricular system. PMID- 24240522 TI - [Incidence of haematological malignancies in adults in Szabolcs-Szatmar-Bereg county, Hungary, between 1983 and 2012. Analysis of data from a thirty-year period]. AB - INTRODUCTION: In their previous work the authors reported 25 years' findings on the incidence of haematological malignancies in Szabolcs-Szatmar-Bereg county, Hungary. However, there are no other studies on this topic available in Hungary. AIM: The aim of the authors was to analyze the incidence of malignant haematological disorders between 1983 and 2012 using data obtained from the leukaemia/lymphoma registry of the Szabolcs-Szatmar-Bereg county. METHOD: Between January 1, 1983 and December 31, 2012, 3964 adult patients with newly diagnosed haematological malignancy were recorded in the registry. Patients with myelodysplastic syndrome or monoclonal gammopathy were not registered. RESULTS: The annual number of newly diagnosed patients indicated an increasing tendency of malignant haematological disorders. The increase was primarily due to the increasing number of patients with non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, and essential thrombocythaemia. CONCLUSIONS: These observations are in line with data reported in the international literature. The incidence rate of haematological malignancies in this region of Hungary was similar to data published in populations from Western European countries and the United States. PMID- 24240523 TI - [Health survey of ambulance workers with a generic questionnaire (SF-36)]. AB - INTRODUCTION: The high work-related stress among ambulance workers is a widely known a phenomenon. AIM: The aim of the authors was to asses self-reported health status of ambulance workers. METHOD: An anonym self-fill-in questionnaire applying SF-36 was used among workers from the northern and western regions of Hungarian National Ambulance Service. RESULTS: Based on the dimensions of the SF 36 questionnaire the responders considered their "Physical Functioning" the best, while "Vitality" was regarded the worst. The more time an employee have been worked at the Ambulance Service the worse his health was in the first four dimensions including "Physical Functioning", "Role-Physical", "Bodily Pain" and "General Health": p<0.001. Those working in part-time jobs considered their health in all dimensions worse. The respondents who did some kind of sports hold their health in all dimensions better (p<0.001). The workers with higher body mass index regarded their health status worse, in four dimensions: "Physical Functioning" (p = 0.001), "Role-Physical" (p = 0.013), "General Health" (p<0.001) and "Role-Emotional" (p = 0.05). CONCLUSIONS: According to the subjective perception of health and measurable parameters of health status of workers proved to be insufficient. Poor physical health can lead indirectly to psychological problems, which may lower the quality of the work and can lead to high turn-over. . PMID- 24240524 TI - [Empyema thoracis, hemorrhagic pericarditis and acalculous cholecystitis caused by Eikenella corrodens sepsis]. AB - The authors present a case of a 29-year-old woman who was diagnosed with pneumonia in the left side complicated with pleural effusion and hemorrhagic pericarditis one month after she had undergone tonsillectomy. Eikenella corrodens was identified as pathogenic agent when the empyema was removed during thoracotomy. After the patient was given antibiotic treatment she was discharged from the hospital without any symptoms or complaints. However, one month after she had left the hospital she was readmitted to the surgical unit as an emergency because of acute abdominal complaints. On admission acalculous cholecystitis as well as hemorrhagic pericarditis requiring pericardiocentesis were also observed. A rare cause of sepsis, Eikenella corrodens was identified which resulted in a severe disorder including polyserositis. Pericardiocentesis was performed two times and the patient was given targeted antibiotics and non-steroidal anti inflammatory drugs. She was also treated with antimycotics as she had developed mycosis. After one month the patient recovered and was discharged from the hospital. No further recurrence of symptoms or complaints was observed during follow up. PMID- 24240525 TI - [Importance of the case of coronavirus-associated severe acute respiratory syndrome detected in Hungary in 2005]. AB - Ten years have elapsed since the severe acute respiratory syndrome outbreak, which resulted in more than 8000 cases worldwide with more than 700 deaths. Recently, a new coronavirus, the Middle East Respiratory Syndrome Coronavirus emerged, causing serious respiratory cases and death. By the end of August 2013, 108 cases including 50 deaths were reported. The authors discuss a coronavirus associated severe acute respiratory syndrome, which was detected in Hungary in 2005 and highlight its significance in 2013. In 2005 the patient was hospitalized and all relevant clinical and microbiological tests were performed. Based on the IgG antibody positivity of the serum samples, the patient was diagnosed as having severe acute respiratory syndrome coronavirus infection in the past. The time and source of the infection remained unknown. The condition of the patient improved and he was discharged from the hospital. The case raises the possibility of infections in Hungary imported from remote areas of the world and the importance of thorough examination of patients with severe respiratory syndrome with unknown etiology. PMID- 24240528 TI - Genetics of adverse reactions to haloperidol in a mouse diallel: a drug-placebo experiment and Bayesian causal analysis. AB - Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug-placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, "difference of models" and "multiple-impute matched pairs", are motivated by the Neyman-Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2-53.2%) but also strong effects of epistasis (10.64-25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent of-origin effects contribute strongly to treatment effect heterogeneity for this drug. PMID- 24240529 TI - Hitchhiking of deleterious alleles and the cost of adaptation in partially selfing species. AB - Self-fertilization is generally seen to be disadvantageous in the long term. It increases genetic drift, which subsequently reduces polymorphism and the efficiency of selection, which also challenges adaptation. However, high selfing rates can increase the fixation probability of recessive beneficial mutations, but existing theory has generally not accounted for the effect of linked sites. Here, we analyze a model for the fixation probability of deleterious mutants that hitchhike with selective sweeps in diploid, partially selfing populations. Approximate analytical solutions show that, conditional on the sweep not being lost by drift, higher inbreeding rates increase the fixation probability of the deleterious allele, due to the resulting reduction in polymorphism and effective recombination. When extending the analysis to consider a distribution of deleterious alleles, as well as the average fitness increase after a sweep, we find that beneficial alleles generally need to be more recessive than the previously assumed dominance threshold (h < 1/2) for selfing to be beneficial from one-locus theory. Our results highlight that recombination aiding the efficiency of selection on multiple loci amplifies the fitness benefits of outcrossing over selfing, compared to results obtained from one-locus theory. This effect additionally increases the parameter range under which obligate outcrossing is beneficial over partial selfing. PMID- 24240530 TI - The role of a pollen-expressed Cullin1 protein in gametophytic self incompatibility in Solanum. AB - We previously isolated a pollen factor, ui6.1, which encodes a Cullin1 protein (CUL1) that functions in unilateral interspecific incompatibility (UI) in Solanum. Here we show that CUL1 is also required for pollen function in self incompatibility (SI). We used RNA interference (RNAi) to reduce CUL1 expression in pollen of Solanum arcanum, a wild SI tomato relative. Hemizygous T0 plants showed little or no transmission of the transfer DNA (T-DNA) through pollen when crossed onto nontransgenic SI plants, indicating that CUL1-deficient pollen are selectively eliminated. When crossed onto a related self-compatible (SC) accession lacking active S-RNase, pollen transmission of the T-DNA followed Mendelian ratios. These results provide further evidence for functional overlap between SI and UI on the pollen side and suggest that CUL1 mutations will reinforce SI-to-SC transitions in natural populations only if preceded by loss of pistil S-RNase expression. PMID- 24240532 TI - Intracoronary imaging of in-stent atherosclerosis by coronary angioscopy and optical coherence tomography. PMID- 24240533 TI - Starting up microbial enhanced oil recovery. AB - This chapter gives the reader a practical introduction into microbial enhanced oil recovery (MEOR) including the microbial production of natural gas from oil. Decision makers who consider the use of one of these technologies are provided with the required scientific background as well as with practical advice for upgrading an existing laboratory in order to conduct microbiological experiments. We believe that the conversion of residual oil into natural gas (methane) and the in situ production of biosurfactants are the most promising approaches for MEOR and therefore focus on these topics. Moreover, we give an introduction to the microbiology of oilfields and demonstrate that in situ microorganisms as well as injected cultures can help displace unrecoverable oil in place (OIP). After an initial research phase, the enhanced oil recovery (EOR) manager must decide whether MEOR would be economical. MEOR generally improves oil production but the increment may not justify the investment. Therefore, we provide a brief economical assessment at the end of this chapter. We describe the necessary state of-the-art scientific equipment to guide EOR managers towards an appropriate MEOR strategy. Because it is inevitable to characterize the microbial community of an oilfield that should be treated using MEOR techniques, we describe three complementary start-up approaches. These are: (i) culturing methods, (ii) the characterization of microbial communities and possible bio-geochemical pathways by using molecular biology methods, and (iii) interfacial tension measurements. In conclusion, we hope that this chapter will facilitate a decision on whether to launch MEOR activities. We also provide an update on relevant literature for experienced MEOR researchers and oilfield operators. Microbiologists will learn about basic principles of interface physics needed to study the impact of microorganisms living on oil droplets. Last but not least, students and technicians trying to understand processes in oilfields and the techniques to examine them will, we hope, find a valuable source of information in this review. PMID- 24240534 TI - Arabidopsis SABRE and CLASP interact to stabilize cell division plane orientation and planar polarity. AB - The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes. PMID- 24240535 TI - Quadriceps rate of force development affects gait and function in people with knee osteoarthritis. AB - OBJECTIVE: Quadriceps weakness exists in people with knee osteoarthritis (OA), but other muscle factors like rate of force development (RFD) may also be affected by knee OA. The purpose of this study was to determine if people with knee OA have deficits in quadriceps RFD, determine if quadriceps RFD would improve predicting knee joint power absorption and generation during free and fast walking, and determine if RFD would improve predicting functional outcomes. METHODS: 26 subjects with knee OA and 23 healthy control subjects performed maximal voluntary isometric strength (MVIC) and RFD measures of the quadriceps. Subjects also underwent a 3-D motion analysis of both self-selected free and self selected fast walking speeds. Joint kinetics were calculated from inverse dynamics. RESULTS: RFD was not different by group (p = 0.763), however, the OA subjects generated the highest peak RFD at a lower % MVIC (p = 0.008). Controls walked significantly faster at both free and fast walking speeds (p = 0.001, p = 0.029). Knee angles at heel strike and peak knee extension were lower (p = 0.004, p = 0.027) in the OA group. During fast walking knee power generation was higher in controls (p = 0.028). MVIC and force of highest peak RFD predicted KOOS-ADL score in the OA subjects, but only MVIC predicted stair climbing time. CONCLUSIONS: The submaximal force at which peak RFD occurs plays a significant role in knee joint power as well as functional measures in the OA subjects, providing further evidence that factors other than maximal strength are also important in people with knee OA. PMID- 24240536 TI - Use of motor abundance in old adults in the regulation of a narrow-based stance. AB - PURPOSE: The ability to maintain stable balance while standing decreases with age. The body must coordinate multiple joints using "freeze" or "free" strategy, or a combination of both to ensure balance stability. The purpose of this study was to examine age-related changes in the use of motor abundance during upright stance on a narrow base without visual input. METHODS: Uncontrolled manifold (UCM) analysis was used to decompose the movement variability of joints into goal equivalent variability (GEV) and non-goal-equivalent variability (NGEV). The ratio between GEV and NGEV (UCM(ratio)) quantifies the joint coordination related to postural stability, and a high UCM(ratio) value indicates flexible control of joints. To perform balance tests, participants in this study (healthy young and old adults, 20 each) were asked to stand on a flat platform and on narrow wooden blocks with their eyes open and then eyes closed. RESULTS: In upright balance tests, both old and young adults maintained postural stability. GEV was greater than NGEV across all participants and conditions. However, GEV was higher in the young adults than in the old adults, whereas NGEV was higher in the old adults than in the young adults. Therefore, the old adults exhibited a lower UCM(ratio) than the young adults. CONCLUSION: The old adults were unable to exploit motor abundance and used a less flexible multi-joint coordination pattern to achieve stable balance. The UCM(ratio) value reflects the quality of postural control and can be used for assessing joint coordination in balance disorders. PMID- 24240537 TI - Real-time estimation of prostate tumor rotation and translation with a kV imaging system based on an iterative closest point algorithm. AB - Previous studies have shown that during cancer radiotherapy a small translation or rotation of the tumor can lead to errors in dose delivery. Current best practice in radiotherapy accounts for tumor translations, but is unable to address rotation due to a lack of a reliable real-time estimate. We have developed a method based on the iterative closest point (ICP) algorithm that can compute rotation from kilovoltage x-ray images acquired during radiation treatment delivery. A total of 11 748 kilovoltage (kV) images acquired from ten patients (one fraction for each patient) were used to evaluate our tumor rotation algorithm. For each kV image, the three dimensional coordinates of three fiducial markers inside the prostate were calculated. The three dimensional coordinates were used as input to the ICP algorithm to calculate the real-time tumor rotation and translation around three axes. The results show that the root mean square error was improved for real-time calculation of tumor displacement from a mean of 0.97 mm with the stand alone translation to a mean of 0.16 mm by adding real-time rotation and translation displacement with the ICP algorithm. The standard deviation (SD) of rotation for the ten patients was 2.3 degrees , 0.89 degrees and 0.72 degrees for rotation around the right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively. The correlation between all six degrees of freedom showed that the highest correlation belonged to the AP and SI translation with a correlation of 0.67. The second highest correlation in our study was between the rotation around RL and rotation around AP, with a correlation of -0.33. Our real-time algorithm for calculation of rotation also confirms previous studies that have shown the maximum SD belongs to AP translation and rotation around RL. ICP is a reliable and fast algorithm for estimating real-time tumor rotation which could create a pathway to investigational clinical treatment studies requiring real-time measurement and adaptation to tumor rotation. PMID- 24240538 TI - B to B: surviving and thriving in the new health care economy. PMID- 24240539 TI - The failed total ankle. PMID- 24240540 TI - IL-10 gene polymorphisms and their association with immune traits in four rabbit populations. AB - Interleukin-10 (IL-10) has been recently identified as a multifunctional cytokine, because of its close link with immunoregulation and anti-inflammatory responses. This study investigated the association of IL-10 genetic polymorphisms with the immune traits of New Zealand white rabbits (N-W), Fujian yellow rabbits (F-Y) and their reciprocal crosses (N-Y and Y-N, respectively). SNPs on five exons of the IL-10 gene were genotyped in 204 healthy rabbits via PCR-SSCP and DNA sequencing. Two SNPs (A1435G and G1519A, both were synonymous mutations) and six genotypes (AA, BB, CC, AB, AC and BC) were found on exon 3 and one SNP (T base insertion between loci 2532 and 2533, which caused a frameshift mutation), and three genotypes (OO, TT and TO) were present on exon 4. Allele A was the most frequent allele on exon 3 (from 0.548 to 0.771), whereas O was the most frequent on exon 4 (from 0.808 to 0.968). These four populations were all in Hardy Weinberg equilibrium on both exon3 and exon4. Association analysis between polymorphisms and immune parameters showed that SNPs on exon 3 were significantly associated with immune traits, while SNP on exon 4 may not significantly affect immune traits, but the mechanism is yet to be further studied. PMID- 24240541 TI - Physiological and production response of dairy goats bred in a tropical climate. AB - The aim of this work was to determine the adaptability of Saanen and 1/2Saanen * 1/2Anglo-Nubian (1/2S1/2AN) goats bred in tropical climates. The study included 30 goats, 15 Saanen and 15 1/2S1/2AN. The data was collected during the rainy and dry seasons. During the whole experimental period, the environment variables were recorded, as well as rectal temperature (RT), superficial temperature (ST), respiratory rate (RR) and heart rate (HR) and milk production (MP). The adaptability coefficient (AC) was calculated for both genotypes. The averages were evaluated by ANOVA at 5% probability. There was a genotype and period of year effect, as well as the interaction genotype * period of year. Pearson's simple correlation analysis was then carried out between milk production and physiological and environment variables. There was a statistical difference (p < 0.05) between the seasons for RT, ST and RR. RT, RR and HR were lower for 1/2S1/2AN than Saanen goats, regardless of the season. MP was greater in the dry season (p < 0.05) (2.52 +/- 0.50 kg/day for 1/2S1/2AN and 2.41 +/- 0.38 kg/day for Saanen) than the rainy season (2.17 +/- 0.27 kg/day for 1/2S1/2AN and 2.28 +/ 0.53 kg/day for Saanen). The MP correlations were very significant (p < 0.05), however low and negative, where it was higher when correlated with RR in Saanen goats. Under the conditions of the present study, it is concluded that the goats were influenced by climatic factors, where the rainy period was more likely to cause thermal stress in the animals. PMID- 24240542 TI - Identification of key signaling molecules involved in the activation of the swelling-activated chloride current in human glioblastoma cells. AB - The swelling-activated chloride current (I Cl,Vol) is abundantly expressed in glioblastoma (GBM) cells, where it controls cell volume and invasive migration. The transduction pathway mediating I Cl,Vol activation in GBM cells is, however, poorly understood. By means of pharmacological and electrophysiological approaches, on GL-15 human GBM cells we found that I Cl,Vol activation by hypotonic swelling required the activity of a U73122-sensitive phospholipase C (PLC). I Cl,Vol activation could also be induced by the membrane-permeable diacylglycerol (DAG) analog OAG. In contrast, neither calcium (Ca(2+)) chelation by BAPTA-AM nor changes in PKC activity were able to affect I Cl,Vol activation by hypotonic swelling. We further found that R59022, an inhibitor of diacylglycerol kinase (DGK), reverted I Cl,Vol activation, suggesting the involvement of phosphatidic acid. In addition, I Cl,Vol activation required the activity of a EHT1864-sensitive Rac1 small GTPase and the resulting actin polymerization, as I Cl,Vol activation was prevented by cytochalasin B. We finally show that I Cl,Vol can be activated by the promigratory fetal calf serum in a PLC- and DGK-dependent manner. This observation is potentially relevant because blood serum can likely come in contact with glioblastoma cells in vivo as a result of the tumor-related partial breakdown of the blood-brain barrier. Given the relevance of I Cl,Vol in GBM cell volume regulation and invasiveness, the several key signaling molecules found in this study to be involved in the activation of the I Cl,Vol may represent potential therapeutic targets against this lethal cancer. PMID- 24240544 TI - Non-physician-led exercise stress testing is a safe and effective practice. AB - Exercise stress testing is a non-invasive procedure that provides diagnostic and prognostic information for the evaluation of several pathologies, including arrhythmia provocation, assessment of exercise capacity, and coronary heart disease. Historically, exercise tests were directly supervised by physicians; however, cost-containment issues and time constraints on physicians have encouraged the use of health professionals with specific training and experience to supervise selected exercise stress tests. Evidence suggests that non-physician led exercise stress testing is a safe and effective practice with similar morbidity and mortality rates as those performed or supervised by a physician. PMID- 24240543 TI - Cholesterol forms and traditional lipid profile for projection of atherogenic dyslipidemia: lipoprotein subfractions and erythrocyte membrane cholesterol. AB - Atherogenic dyslipidemia characterized by abnormal changes in plasma lipid profile such as low high-density lipoprotein (HDL) and increased triglyceride (TG) levels is strongly associated with atherosclerotic diseases. We aimed to evaluate the levels of pro- and antiatherogenic lipids and erythrocyte membrane cholesterol (EMC) content in normo- and dyslipidemic subjects to investigate whether EMC content could be a useful marker for clinical presentation of atherogenic dyslipidemia. Low-density lipoprotein (LDL), HDL and their subfraction levels and erythrocyte lipid content were determined in 64 normolipidemic (NLs), 42 hypercholesterolemic (HCs) and 42 mixed-type dyslipidemic subjects (MTDs). Plasma atherogenic lipid indices [small-dense LDL (sdLDL)/less-dense HDL (LHDL), TC/HDL-C, TG/HDL-C and Apo B/AI] were higher in MTDs compared to NLs (p < 0.001). The highest sdLDL level was observed in HCs (p < 0.01). Despite a slight increase in EMC level in dyslipidemic subgroups, the difference was not statistically significant. A significant negative correlation, however, was observed between EMC and sdLDL/LHDL in HCs (p < 0.035, r = -0.386). Receiver operating characteristic curves to predict sdLDL level showed that TG and EMC levels had higher area under curve values compared to other parameters in HCs. We showed that diameters of larger LDL and HDL particles tend to shift toward smaller values in MTDs. Our results suggest that EMC content and TG levels may be a useful predictor for sdLDL level in hypercholesterolemic patients. PMID- 24240545 TI - Fragmented QRS complexes-a novel but underutilized electrocardiograhic marker of heart disease. AB - The electrocardiogram is the mainstay approach for diagnosing a myocardial infarction (MI). The diagnosis of an old MI and the identification of myocardial scar via the electrocardiogram are difficult because there are no other specific signs for a non-Q-wave MI. In this article, we will review the fragmented QRS and its role in identifying myocardial scar and depolarization abnormalities in patients with coronary artery disease. PMID- 24240546 TI - A personal perspective: can legislated state regional STEMI centers provide timely STEMI treatment while overlooking early fibrinolysis? AB - Because a patient's odds of surviving a ST-Elevation Myocardial Infarction (STEMI) depend on how much myocardium is salvaged by treatment, this article presents information about whether the Missouri Regional STEMI Center Program, created by state law, can provide STEMI treatment in time to preserve the ischemic heart muscle. The law states that "Patients who suffer a STEMI, as defined in Section 190.100, shall be transported to a STEMI Center." Administration is by the Missouri Department of Health and Senior Services (DHSS) which states that the preferred treatment for STEMI is percutaneous coronary intervention (PCI) and does not mention fibrinolysis when eligible. Level I and II receiving centers are hospitals with catheterization laboratories that perform a high volume of PCI procedures. Level I centers have heart surgery facilities. Level II centers may have such services or may have prompt access to nearby facilities. The law states that the smaller level III and IV hospitals are to stabilize patients for transport to a level I or II center. Although the law lists no patients to be excluded from transport, DHSS is limiting the program to patients picked up at the scene by ambulance. The majority of STEMI patients going to community hospitals by car are not included. Data are presented, showing that when blood flow is restored to the ischemic muscle during infarction before the end of the second hour of symptoms most can be saved. Data also show that only a small fraction of patients with PCI receives it before the end of the second hour of symptoms, whereas many more fibrinolysis patients were treated within 2 hours. Clinical practice data are given, showing mortality rates to increase with longer times to treatment. This information clearly defines timely treatment of STEMI to be that carried out before the end of the second hour of symptoms. Setting forth details of how long after symptom onset will be required to get to the catheterization laboratory shows that not many Missouri Program STEMI patients will get there before the end of the second hour of symptoms when salvageable heart muscle remains. The second thrust of this article is to draw attention to the seriousness of the Missouri Program overlooking the extremely important early fibrinolysis option for achieving treatment during the first 2 hours of symptoms. PMID- 24240547 TI - What do patients think about while waiting for myocardial revascularization? AB - OBJECTIVES: Coronary artery disease constitutes a public health issue involving high mortality rates. The objectives of this study were to evaluate the feelings and perception of patients hospitalized before myocardial revascularization and to explore doctor-patient interactions before cardiac surgery with special attention to existential challenges. STUDY DESIGN: A qualitative, exploratory study involving patients admitted to a university teaching hospital in the city of Salvador, Bahia, Brazil, awaiting myocardial revascularization. METHODS: The data were obtained from in-depth interviews that followed a previously defined script based on the study objectives. The data collected at each interview were allocated into content blocks in common with the selected categories and illustrated by quotations from the patients' speech. Twelve patients were interviewed. Data collection was closed when saturation was achieved, in the sense that new main issues did not appear in subsequent dialogues. RESULTS: The various strategies used by the patients to administer their emotions during the period preceding myocardial revascularization highlight the importance that factors of a subjective nature acquire at this specific time in their lives. The patients recognized the benefit of being able to discuss their heart problems as a means of diminishing their fear and anxiety. CONCLUSIONS: It is vital for the medical team to be more supportive and understanding concerning the emotions experienced by the patients in the period preceding myocardial revascularization. This study emphasizes the importance of the task of helping patients administer their perceptions and feelings and even planning their life while awaiting myocardial revascularization. PMID- 24240548 TI - The accuracy of interqual criteria in determining the need for observation versus hospitalization in emergency department patients with chronic heart failure. AB - McKesson's Interqual criteria are one of the medical screening criteria that are widely used in emergency departments (EDs) to determine if patients qualify for observation or inpatient admission. Chronic heart failure (CHF) is one of the most common yet severe cardiovascular diseases seen in the ED with a relatively higher admission rate. This study is to evaluate the accuracy of Interqual criteria in determining observation versus hospitalization need in CHF patients. From January 2009 till December 2010, data from 503 CHF patients were reviewed. One hundred twenty-two patients were observed and 381 patients were admitted. Only one variable (blood urea nitrogen, >=30 mg/dL; odds ratio, 2.44) from Interqual criteria had reached statistical significant difference between observation and hospitalization groups. Our results showed that based on the initial review at ED, clinical variables from Interqual criteria did not appear to help accurately predict the level of care in CHF patient in our patient population. Other clinical variables may need to be added in the criteria for better prediction. PMID- 24240549 TI - Comparing two strategies for emergency department chest pain patients: immediate computed tomography coronary angiography versus delayed outpatient treadmill testing. AB - Chest pain (CP) is a common emergency department (ED) complaint and return visits (recidivism) are common. Recidivism may be related to incomplete evaluation of a patient's complaint. Computed tomography coronary angiography (CTCA) is accurate for diagnosing coronary artery disease (CAD) in patients with CP. We will compare a strategy of immediate CTCA with a strategy of delayed outpatient stress testing and hypothesize that CTCA will reduce recidivism in patients with CP. We conducted a retrospective cohort study comparing strategies for ED patients with CP: immediate CTCA (CT cohort) versus delayed outpatient stress testing (control cohort). Two hundred eighty subjects were included, 140 in each of the strategies. Recidivism within 6 months of the index ED evaluation occurred in 12 subjects from the CT cohort and 18 subjects from the control cohort (9% vs. 13%, P = 0.41). Duration of stay was increased in the CT cohort (456 vs. 417 min, P = 0.031). Immediate CTCA was associated with improved detection of obstructive CAD (8% vs. 1%, P = 0.005). In conclusion, immediate CTCA, when compared with delayed outpatient stress testing, did not reduce ED recidivism for CP. Length of stay was increased in the immediate CTCA cohort. The use of CTCA improved detection of obstructive CAD. PMID- 24240550 TI - Low-risk chest pain patients younger than 40 years do not benefit from admission and stress testing. AB - BACKGROUND: A number of studies have suggested clinical decision rules for patients age <40 who are at low risk for acute coronary syndrome (ACS) and may be safe for discharge from the emergency department. Despite this, many such patients continue to be admitted for observation in low-risk observation units. We hypothesized that patients age <40 without coronary artery disease, with a nonischemic electrocardiogram (ECG), and normal initial troponin I (TnI) who are admitted to a CPU are at very low risk (<1%) for ACS or 30-day major adverse cardiac event (MACE) and would not benefit from observation care. METHODS: This was a prospective, observational study of consecutive patients admitted to the CPU in a large-volume academic urban emergency department. Eligibility criteria included age >18 but <40, American Heart Association low-to-intermediate risk, nonischemic ECGs, and normal initial TnI. Standard descriptive statistics were used for demographics, cardiac comorbidities, and risk scores. Our primary outcomes were CPU ACS rate and 30-day MACE. MACE was defined as death, nonfatal AMI, revascularization, or out of hospital cardiac arrest. A sample size of at least 400 was chosen to have 1% precision about an expected outcome rate of 0.3% (based on prior CPU data of patients of all ages). Confidence intervals (CIs) were calculated using the refined Wilson simple asymptotic method with continuity correction. All patients were called at 30 days. All charts on index visit and any subsequent visit within 30 days were reviewed using standardized chart abstractions forms by 2 trained abstractors blinded to the hypothesis of the study. A Social Security Death Index search was performed on all patients. RESULTS: Three hundred eighty-four patients accounting for 403 CPU admissions were enrolled over a 28-month period. Mean age was 34.3 +/- 4.5; 42% were women; and 89%, 8%, 2%, and 1% had Thrombolysis in Myocardial Infarction scores of 0, 1, 2, and 3, respectively. No patient had an abnormal TnI. The ACS rate was 0 (95% CI, 0-0.8%). The 30-day MACE rate was 0 (95% CI, 0-0.8%). Forty-two percentage of these patients received stress testing but 0 (95% CI, 0-1.8%) were positive. CONCLUSIONS: Patients age <40 with a normal ECG and normal first biomarker have <1% risk of ACS or 30-day MACE, such that admission and stress testing are of no benefit. PMID- 24240551 TI - Resource consumption and healthcare costs of acute coronary syndrome: a retrospective observational administrative database analysis. AB - The objective of this study was to estimate resource consumption and direct healthcare costs of patients with a first hospitalization for acute coronary syndrome (ACS) in 2008 in the Piedmont Region, Italy. Subjects hospitalized with a first episode of ACS in 2008 were selected from the regional hospital discharge database. All hospitalizations, drug prescriptions, and outpatient episodes of care in the 12 months following discharge were considered to estimate resource consumption and direct healthcare costs from the Piedmont Regional Health Service perspective. The analysis was carried out separately for ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA) populations. In the accrual period, 7765 subjects (1.750/00 of the total population) were hospitalized for ACS (64.2% men). The average age was 66.5 for men and 75.4 for women. The average in-hospital mortality was 6.5% (n = 508). The total ACS population was classified as: STEMI 45.2%, NSTEMI 29.4%, and UA 25.4%. The average yearly costs per patient alive at the end of follow-up (n = 6851) were 14,160.8&OV0556; (18,678.7 USD): 83.9% for inpatient admissions [11,881.2&OV0556; (15,671.8 USD)], 9.3% for drugs [1311.6&OV0556; (1730.1 USD)], 5.0% for diagnostic and therapeutic procedures and outpatient visits [708.2&OV0556; (934.1 USD)], and 1.8% for 1-day hospital stays [259.8&OV0556; (342.7 USD)]. The average yearly direct healthcare costs by ACS event were 14,984.5&OV0556; (19,765.2 USD) for STEMI, 14,554.1&OV0556; (19,197.4 USD) for NSTEMI, and 12,481.5&OV0556; (16,463.6 USD) for UA. In each subpopulation, costs were significantly higher for men than for women. ACS imposes a significant burden in terms of morbidity and mortality and generates major public health service costs. PMID- 24240552 TI - Cyclic pressure and angiotensin II influence the biomechanical properties of aortic valves. AB - Hypertension is a known risk factor for aortic stenosis. The elevated blood pressure increases the transvalvular load and can elicit inflammation and extracellular matrix (ECM) remodeling. Elevated cyclic pressure and the vasoactive agent angiotensin II (Ang II) both promote collagen synthesis, an early hallmark of aortic sclerosis. In the current study, it was hypothesized that elevated cyclic pressure and/or angiotensin II decreases extensibility of aortic valve leaflets due to an increase in collagen content and/or interstitial cell stiffness. Porcine aortic valve leaflets were exposed to pressure conditions of increasing magnitude (static atmospheric pressure, 80, and 120 mmHg) with and without 10-6 M Ang II. Biaxial mechanical testing was performed to determine extensibility in the circumferential and radial directions and collagen content was determined using a quantitative dye-binding method at 24 and 48 h. Isolated aortic valve interstitial cells exposed to the same experimental conditions were subjected to atomic force microscopy to assess cellular stiffness at 24 h. Leaflet tissue incubated with Ang II decreased tissue extensibility in the radial direction, but not in the circumferential direction. Elevated cyclic pressure decreased extensibility in both the radial and circumferential directions. Ang II and elevated cyclic pressure both increased the collagen content in leaflet tissue. Interstitial cells incubated with Ang II were stiffer than those incubated without Ang II while elevated cyclic pressure caused a decrease in cell stiffness. The results of the current study demonstrated that both pressure and Ang II play a role in altering the biomechanical properties of aortic valve leaflets. Ang II and elevated cyclic pressure decreased the extensibility of aortic valve leaflet tissue. Ang II induced direction specific changes in extensibility, demonstrating different response mechanisms. These findings help to provide a better understanding of the responses of aortic valves to mechanical and biochemical changes that occur under hypertensive conditions. PMID- 24240553 TI - Biomechanics of subdural hemorrhage in American football: review of the literature in response to rise in incidence. AB - The number of catastrophic head injuries recorded during the 2011 football season was the highest since data collection began in 1984--the vast majority of these cases were secondary to subdural hemorrhage (SDH). The incidence of catastrophic head injury continues to rise: the average yearly incidence from 2008 to 2012 was 238% that of the average yearly incidence from 1998 to 2002. Greater than 95% of the football players who suffered catastrophic head injury during this period were age 18 or younger. Currently, the helmet industry utilizes a standard based on data obtained at Wayne State University approximately 50 years ago that seeks to limit severity index--a surrogate marker of translational acceleration. In this manuscript, we utilize a focused review of the literature to better characterize the biomechanical factors associated with SDH following collisions in American football and discuss these data in the context of current helmet standard. Review of the literature indicates the rotational acceleration (RA) threshold above which the risk of SDH becomes appreciable is approximately 5,000 rad/s(2). This value is not infrequently surmounted in typical high school football games. In contrast, translational accelerations (TAs) experienced during even elite-level impacts in football are not of sufficient magnitude to result in SDH. This information raises important questions about the current helmet standard--in which the sole objective is limitation of TA. Further studies will be necessary to better define whether helmet constructs and quality assurance standards designed to limit RA will also help to decrease the risk of catastrophic head injury in American football. PMID- 24240554 TI - The N-terminal domains of spider silk proteins assemble ultrafast and protected from charge screening. AB - Web spiders assemble spidroin monomers into silk fibres of unrivalled tensile strength at remarkably high spinning speeds of up to 1 m s(-1). The spidroin N terminal domain contains a charge-driven, pH-sensitive relay that controls self association by an elusive mechanism. The underlying kinetics have not yet been reported. Here we engineer a fluorescence switch into the isolated N-terminal domain from spidroin 1 of the major ampullate gland of the nursery web spider E. australis that monitors dimerization. We observe ultrafast association that is surprisingly insensitive to salt, contrasting the classical screening effects in accelerated, charged protein interfaces. To gain deeper mechanistic insight, we mutate each of the protonatable residue side chains and probe their contributions. Two vicinal aspartic acids are critically involved in an unusual process of accelerated protein association that is protected from screening by electrolytes, potentially facilitating the rapid synthesis of silk fibres by web spiders. PMID- 24240555 TI - Supplemental scleral buckling for inferior retinal detachment in silicone oil filled eyes. AB - PURPOSE: To evaluate the efficiency of treating selected cases of inferior retinal detachment in silicone oil-filled eyes using a supplemental scleral buckling with external drainage of subretinal fluid, versus performing a second vitreoretinal surgery and silicone oil endotamponade. METHODS: A prospective interventional pilot study that was performed on silicone oil-filled eyes with inferior retinal detachment. Twenty-three eyes of 23 consecutive patients were alternatively distributed between 2 groups: Group A included 12 eyes treated with supplemental scleral buckling with drainage of subretinal fluid and without the removal of silicone oil, and Group B included 11 eyes treated with silicone oil removal, vitreoretinal surgery, and reinjection of silicone oil. The preoperative data included indications and details of primary vitreoretinal surgery, cause of retinal redetachment, subretinal fluid, grade of proliferative vitreoretinopathy, lens status, and the duration between primary vitreoretinal surgery and reoperation. The postoperative examination included the best-corrected visual acuity, retina status, proliferative vitreoretinopathy, silicone oil, and any reported complication. Follow-up examinations were scheduled at Day 1, weekly for 1 month, and monthly thereafter till the end of the follow-up period which extended for at least 2 months after silicone oil removal. RESULTS: The average number of detached clock hours per eye was 2.7 in Group A and 2.4 in Group B, caused by a mean of 1.58 +/- 0.80 break per eye in Group A and 1.48 +/- 0.66 break per eye in Group B. The mean interval between the primary vitreoretinal surgery and the scleral buckling procedure in Group A patients was 2.83 +/- 1.22 months (range, 1-5 months), while in Group B, the mean interval between the primary and the secondary vitreoretinal surgeries was 3.00 +/- 1.61 months (range, 1-6 months). The mean operative time was statistically significantly (P < 0.05) shorter in Group A (38.7 +/- 11.2 minutes) than in Group B (65.3 +/- 15.1 minutes). The mean follow-up duration was 15.00 +/- 3.22 months in Group A and 14.18 +/- 2.99 months in Group B. After silicone oil removal, the retina was attached in 10 of the 12 eyes (83.3%) and redetached in 2 eyes (16.7%) in Group A, while in Group B, the retina was attached in 9 of the 11 eyes (81.8%) and redetached in 2 eyes (18.2%) after silicone oil removal. The mean logarithm of the minimum angle of resolution best-corrected visual acuity has improved from 1.82 +/- 0.72 to 1.36 +/- 0.52 in Group A patients (P > 0.05) and from 1.93 +/- 0.74 to 1.55 +/- 0.63 in Group B patients (P > 0.05) at the end of the follow-up duration. CONCLUSION: For selected cases of inferior retinal detachment in silicone oil-filled eyes, supplemental scleral buckling could be as effective as a second vitreoretinal surgery. Scleral buckling could offer a faster, less invasive, and better economic alternative to repeated vitreoretinal surgery for treatment of such cases. PMID- 24240556 TI - Characteristics of cystoid spaces in type 2 idiopathic macular telangiectasia on spectral domain optical coherence tomography images. AB - PURPOSE: To investigate the morphologic and topographic characteristics of intraretinal cystoid spaces in eyes with Type 2 idiopathic macular telangiectasia (MacTel 2). METHODS: Using B-scan and en face images of eyes with MacTel 2 taken from a spectral domain optical coherence tomography database, the circularities and mean gray values of the cystoid spaces were measured to determine their boundaries and reflectivity. The characteristics of cystoid spaces in MacTel 2 eyes were compared with those in eyes with Type 1 idiopathic macular telangiectasia (MacTel 1), retinal vein occlusion, and diabetic macular edema, which are caused by vascular leakage. The cystoid spaces of en face optical coherence tomography images were matched with fluorescein angiographic images. RESULTS: The circularity of the cystoid spaces in B-scan and en face optical coherence tomography images of 16 eyes with MacTel 2 was lower than that of eyes with MacTel 1 (P = 0.004 and P = 0.003, respectively), retinal vein occlusion (P < 0.001 and P < 0.001, respectively), and diabetic macular edema (P < 0.001 and P < 0.001, respectively). The mean gray value ratio of the cystoid spaces of eyes with MacTel 2 was lower than that of eyes with MacTel 1 (P = 0.002) and diabetic macular edema (P < 0.001). In eyes with MacTel 2, the cystoid spaces were located in the foveal center or parafoveal area. CONCLUSION: Characteristics of cystoid spaces of eyes with MacTel 2 were different from those in eyes with MacTel 1, retinal vein occlusion, and diabetic macular edema. The irregular boundaries and low reflectivity of the cystoid spaces in MacTel 2 may represent the degenerative origin of the disease. PMID- 24240557 TI - Influence of axial length and postinjection reflux on sustained intraocular pressure elevation as a result of intravitreal anti-vascular endothelial growth factor therapy. AB - PURPOSE: To assess an association of axial length (AL) or postinjection reflux with transient or sustained intraocular pressure (IOP) elevation in patients with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor injections. METHODS: One hundred and forty-seven eyes from 74 consecutive patients with neovascular age-related macular degeneration who presented to a single physician over a 2-month period had ALs measured by IOLMaster. Twenty-one patients had preinjection and immediate postinjection IOP measured and immediate reflux assessed. RESULTS: Overall, 9.5% of eyes had been identified with sustained IOP elevation in our previous study. Axial length did not significantly differ between eyes that had (AL, 23.96 +/- 0.66 mm; n = 14) and had not experienced sustained IOP elevation (AL, 23.44 +/- 1.24 mm; n = 133; P = 0.12, t-test). By linear regression analysis, the relationship between experiencing sustained IOP elevation and AL was not statistically significant (R2 = 0.0165; P = 0.121). The relationship between AL and immediate postinjection IOP elevation was also not statistically significant (R2 = 0.0001; P = 0.97). Immediate postinjection IOP increase did differ between eyes without reflux (30.2 +/- 9.3 mmHg; n = 12) and those with reflux (1.1 +/- 7.2; n = 9; P < 0.001). CONCLUSION: Axial length does not seem to be a predictor of transient or sustained IOP elevation. Repeated trabecular meshwork trauma related to the absence or presence of reflux and immediate postinjection IOP elevation may be a contributing factor. PMID- 24240558 TI - Hemorrhagic complications of optic nerve head drusen on spectral domain optical coherence tomography. AB - PURPOSE: To describe the clinical features of hemorrhagic complications secondary to optic nerve head drusen (ONHD) using spectral domain optical coherence tomography (SD-OCT). METHODS: Sixty-three consecutive patients with SD-OCT documented ONHD who presented at Seoul National University Bundang Hospital from December 2009 to July 2012 were included. Full ophthalmologic examinations, including fundus photographs, SD-OCT, fundus angiography, and visual field tests were analyzed in a total of 101 ONHD-positive eyes from 63 patients. RESULTS: Hemorrhagic ONHD complications were found in 7 eyes (7%) from a total of 101 eyes with ONHD. All of them had buried ONHD (visualized with SD-OCT) and myopia (mean spherical equivalent = -4.00 +/- 2.35 diopters). Patients with ONHD hemorrhagic complications had smaller disk diameters than patients without hemorrhagic complications (1,308 +/- 166 vs. 1,555 +/- 217 MUm, P = 0.004). Peripapillary hemorrhages were classified into the following 3 types based on SD-OCT findings: subretinal (6 eyes, 86%), retinal (5 eyes, 71%), and vitreous hemorrhage (4 eyes, 57%). Six patients (86%) complained of the recent onset of visual symptoms, but visual acuities at presentation were 20/20 in all patients. In the three patients who were followed up, most hemorrhages were absorbed without complications. CONCLUSION: Peripapillary hemorrhage can often occur in patients with buried ONHD and small disk diameters. As SD-OCT can be used to visualize ONHD beneath hemorrhage, it is helpful with the differential diagnosis and follow-up evaluation. PMID- 24240559 TI - Diagnostic and therapeutic challenges. PMID- 24240560 TI - Treat-and-extend bevacizumab for neovascular age-related macular degeneration: the importance of baseline characteristics. AB - PURPOSE: To evaluate the factors affecting visual and anatomical outcomes and the number of intravitreal bevacizumab injections required in the treatment of neovascular age-related macular degeneration using a treat-and-extend regimen. METHODS: Retrospective consecutive case series. The charts of subjects treated with intravitreal bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen over a 12-month period were reviewed. The key variables explored were patient age, phakic status, posterior vitreous detachment status, baseline best-corrected visual acuity (BCVA), baseline central macular thickness (CMT), and type of chorodial neovascularization. The primary outcome measures were improvement in BCVA of 3 logMAR lines or more, maintenance of BCVA within 3 logMAR lines of baseline, number of intravitreal injections delivered over a 12-month period, and final CMT on optical coherence tomography. RESULTS: A total of 230 eyes met the criteria. Mean presenting BCVA was Snellen 20/55 (0.44 logMAR) and mean final BCVA was Snellen 20/44 (0.35 logMAR) (P < 0.001). A total of 23.5% (95% confidence interval [CI], 18.5-29.4%) of the subjects demonstrated an improvement in BCVA of 3 or more logMAR lines, whereas 96.5% (95% CI, 93.3 98.2%) of the subjects lost fewer than 3 logMAR lines. Mean CMT on optical coherence tomography changed from a baseline average of 373.1 MUm (95%CI, 360.3 386.1 MUm) to a final average of 305.5 MUm (95% CI, 290.0-316.0 MUm). The average number of injections during the 12-month period was 9.2 (95% CI, 9.0-9.4). Posterior vitreous detachment was associated with fewer injections on univariate and multivariate analysis (8.7 injections in the posterior vitreous detachment group versus 9.8 in the non-posterior vitreous detachment group, P < 0.001). Patients with poorer presenting BCVA and greater baseline CMTs were more likely to demonstrate a 3 or more logMAR line improvement in BCVA. Thinner final CMTs were independently associated with thinner presenting CMTs and fewer injections. CONCLUSION: Favorable visual and anatomical outcomes may be achieved with intravitreal bevacizumab in the treatment of neovascular age-related macular degeneration using a treat-and-extend regimen. Our study suggests that posterior vitreous detachment may play a role in the efficacy of intravitreal bevacizumab during the treatment of neovascular age-related macular degeneration. PMID- 24240561 TI - Diagnostic and therapeutic challenges. PMID- 24240562 TI - Extramacular drainage of subretinal fluid during vitrectomy for macular hole retinal detachment in high myopia. AB - PURPOSE: To compare surgical outcomes between subretinal fluid drainage through the macular hole (MH) and through sites other than the MH during vitrectomy for MH retinal detachment in highly myopic eyes. METHODS: Retrospective analysis was performed on the medical records of 41 patients who underwent vitrectomy for MH retinal detachment in highly myopic eyes. Group M included eyes in which subretinal fluid was drained through MH. Group E included eyes in which subretinal fluid was drained through an extramacular break or retinotomy. Pre- and postoperative visual acuity, reattachment rate, and MH closure rate were investigated. RESULTS: Primary retinal reattachment was achieved in 13 of 21 eyes (62%) in Group M and in 19 of 20 eyes (95%) in Group E (P = 0.020). The MH was closed more frequently in Group E (15 eyes) than in Group M (7 eyes; P = 0.012). Ambulatory vision of 20/400 or better was achieved in 16 eyes in Group E and in 10 eyes in Group M (P = 0.033). CONCLUSION: Extramacular drainage of subretinal fluid resulted in better outcomes than the conventional procedure of drainage through the MH. PMID- 24240563 TI - Characteristics of central serous chorioretinopathy complicated by focal choroidal excavation. AB - PURPOSE: To investigate the characteristics of central serous chorioretinopathy complicated by focal choroidal excavation (FCE) using fundus angiography and optical coherence tomography (OCT). METHODS: A retrospective single-institution study. We reviewed the charts of 7 eyes of 7 patients (5 men, 2 women; mean age, 56.9 +/- 9.8 years) with central serous chorioretinopathy complicated by FCE using fundus angiography and OCT. RESULTS: In six of the seven eyes, the points of leakage were at the edge of FCE on OCT. All FCE lesions were hypofluorescent from early to late phase on indocyanine green angiography. All eyes had late phase hyperfluorescence on indocyanine green angiography secondary to choroidal vascular hyperpermeability around the FCE lesion. Five fellow eyes also had choroidal vascular hyperpermeability. The mean subfoveal choroidal thicknesses by swept source high-penetration OCT were 377 MUm and 333 MUm in the fellow eyes, a difference that did not reach significance (P = 0.21). CONCLUSION: Fundus angiography and OCT showed that choroidal circulatory disruption and atrophic retinal pigment epithelium at the FCE lesion might be related to central serous chorioretinopathy complicated by FCE. PMID- 24240564 TI - Association of plasma malondialdehyde with ARMS2 genetic variants and phenotypes in polypoidal choroidal vasculopathy and age-related macular degeneration. AB - PURPOSE: To evaluate the relationships between plasma malondialdehyde (MDA) level and ARMS2 variants and phenotypes in patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD). METHODS: This study is a retrospective case-control study. Plasma MDA was measured in 84 controls, 62 patients with PCV, and 42 patients with nAMD. Participants were genotyped for ARMS2 polymorphism. Phenotypes including bilaterality and greatest linear dimension based on fluorescein angiography (FA GLD) and indocyanine green angiography (ICGA-GLD), were evaluated. RESULTS: Plasma MDA in the PCV and nAMD groups was higher than in the control group (P < 0.001, respectively). For ARMS2 variants, plasma MDA of homozygous high-risk genotype (TT) was higher than that of homozygous low-risk genotype (GG) in all groups (P < 0.001, respectively). Plasma MDA was higher in homozygous high-risk genotype than in heterozygous genotype in the control, PCV, and nAMD groups (P = 0.021, 0.002, and 0.004, respectively). In the nAMD group, there was a correlation between plasma MDA and both FA-GLD (r = 0.418, P = 0.006) and ICGA GLD (r = 0.329, P = 0.033). There was a difference in plasma MDA between patients with unilateral and bilateral lesions in both PCV and nAMD (P = 0.017 and 0.019, respectively). CONCLUSION: This study revealed significant relationships between the plasma MDA level and ARMS2 variants and phenotypes in PCV and nAMD. PMID- 24240565 TI - Multimodal imaging findings in retinal deep capillary ischemia. AB - PURPOSES: To evaluate the multimodal imaging findings in retinal deep capillary ischemia (DCI). METHODS: This was a retrospective review of 5 eyes of 4 patients with sudden onset of paracentral scotomas caused by DCI. Multimodal imaging techniques, including color and red-free photographs, near-infrared reflectance, fluorescein angiography, and spectral-domain optical coherence tomography, were performed in all eyes, and the findings were correlated with microperimetry in two eyes. Imaging findings in DCI were compared with those of a cotton wool spot caused by superficial capillary ischemia (SCI). RESULTS: Unlike SCI, the imaging findings in DCI were subtler during both the acute and chronic phase, but specific optical coherence tomographic findings could readily differentiate these entities. Acute SCI showed inner retinal whitening, edema, and increased reflectivity, whereas acute DCI showed increased reflectivity of middle retinal layers. Chronic DCI showed retinal thinning with middle layer atrophy, whereas chronic SCI showed inner layer atrophy. In one patient, microperimetry showed a paracentral dense scotoma that corresponded well to the optical coherence tomographic findings. CONCLUSION: Deep capillary ischemia may represent a nonspecific finding of retinal ischemia and produces characteristic changes within the middle retinal layers, analogous to a deep cotton wool spot, but with distinct features differing from the superficial cotton wool spot which is seen in SCI. Among the various multimodal imaging techniques, optical coherence tomography seemed to be the most sensitive and specific technique in detecting DCI in both the acute and chronic phases. PMID- 24240566 TI - Differences in anterior cruciate ligament elasticity and force for knee flexion in women: oral contraceptive users versus non-oral contraceptive users. AB - Eighty-two percent of sexually active women aged 15-44 have used oral contraceptive pills (OCP) in the United States. The OCP, an exogenous source of synthetic forms of steroid hormones, prevents ovulation. Hormone changes during the menstrual cycle (MC) are believed to have an impact on anterior cruciate ligament (ACL) laxity due to estrogen. Because the estrogen receptor beta resides on human connective tissue, OCP may have potential impact on tendon and ligament synthesis, structure, and biomechanical properties. Temperature has also been known to have an effect on tissue elasticity. Therefore, the purpose of this study was to investigate the differences in ACL elasticity, force to flex the knee (FFK), and knee flexion-extension hysteresis (KFEH) between OCP users and non-OCP users. To investigate these changes, two different knee temperatures were measured. Nineteen young females were divided into two groups: OCP users and non OCP users. Blood for estradiol serum concentration (E2) was taken before beginning the tests. ACL elasticity, FFK, and KFEH were assessed both at ambient temperature (22 degrees C) and after 38 degrees C warming of the leg to stabilize tissue temperature. Assessments were performed four times during the MC. Throughout the MC, ACL elasticity, FFK, and KFEH fluctuated in non-OCP users, but not in OCP users. At ambient temperature, ACL elasticity was significantly lower and FFK and KFEH were significantly higher in OCP users than non-OCP users (p < 0.05). But, no significant differences in FFK and KFEH between the two groups were found after warming to 38 degrees C. PMID- 24240567 TI - Monitoring liverworts to evaluate the effectiveness of hydroriparian buffers. AB - In the coastal temperate rainforest of British Columbia (BC) in western Canada, government policies stipulate that foresters leave unlogged hydroriparian buffer strips up to 25 m on each side of streams to protect wildlife habitat. At present, studies on the effectiveness of these buffers focus on mammals, birds, and amphibians while there is comparably little information on smaller organisms such as liverworts in these hydroriparian buffers. To address this gap of knowledge, we conducted field surveys of liverworts comparing the percent cover and community composition in hydroriparian forested areas (n = 4 sites, n = 32 plots with nested design) to hydroriparian buffer zones (n = 4 sites, n = 32 plots). We also examined how substrate type affected the cover of liverworts. Liverwort communities in buffers were similar to those in riparian forest areas and most liverworts were found on downed wood. Thus, hydroriparian buffers of 25 35 m on each side in a coastal temperate rainforest effectively provide habitat for liverworts as long as downed wood is left intact in the landscape. Because liverworts are particularly sensitive to changes in humidity, these results may indicate that hydroriparian buffers are an effective management strategy for bryophytes and possibly for a range of other riparian species that are particularly sensitive to forestry-related changes in microclimate. PMID- 24240568 TI - Suicide rates in China from 2002 to 2011: an update. AB - PURPOSES: The aims of this study were: (1) to present the time trend of suicide rate among people aged 15 or above in China over the period 2002-2011 and (2) to examine the current profile of completed suicides during 2009-2011. METHODS: Data on suicide rate in 2002-2011 were provided by the Chinese Ministry of Health (MOH). The trends of region-, gender-, and age-specific suicide rates were examined using Poisson regression models. The mean number of completed suicides for each cohort during 2009-2011 was calculated and a mean national suicide rate was estimated. FINDINGS: The overall suicide rate decreased significantly over the past decade, but rates in young males and rural older adults did not reduce and in fact increased among older adults in both urban and rural areas towards the end of the study period. For 2009-2011, 44 % of all suicides occurred among those aged 65 or above and 79 % among rural residents. The estimated mean national suicide rate was 9.8 per 100,000 and was slightly higher for males than females. CONCLUSION: The benefits of economic growth, such as higher employment and more educational opportunities for the rural population in particular, may have contributed to the reduced suicide rate in China. However, the recent rapid changes in socioeconomic conditions could have increased stress levels and resulted in more suicides, especially among the elderly. Despite the significant reduction reported here, the latest figures suggest the declining trend is reversing. It will be important to continue monitoring the situation and to examine how urbanization and economic changes affect the well-being of 1.3 billion Chinese. PMID- 24240569 TI - Serial block face scanning electron microscopy--the future of cell ultrastructure imaging. AB - One of the major drawbacks in transmission electron microscopy has been the production of three-dimensional views of cells and tissues. Currently, there is no one suitable 3D microscopy technique that answers all questions and serial block face scanning electron microscopy (SEM) fills the gap between 3D imaging using high-end fluorescence microscopy and the high resolution offered by electron tomography. In this review, we discuss the potential of the serial block face SEM technique for studying the three-dimensional organisation of animal, plant and microbial cells. PMID- 24240570 TI - [Medical operations at the 2010 love parade in Duisburg]. AB - On 24 July 2010 the love parade, a large scale open air concert was held in the city of Duisburg to which more than 500,000 guests were expected. During the course of the early evening a major tragic incident occurred in which 21 people were crushed to death and several hundred others were injured. In this article the preparation of the emergency and rescue services prior to the event is described and their operations entailing more than 1,600 staff members from all over Germany are illustrated. The article focuses on the mass casualty incident which took place in the tunnel in the early evening of that day. PMID- 24240571 TI - A Dictyostelium cellobiohydrolase orthologue that affects developmental timing. AB - Dictyostelium discoideum is a facultative multicellular amoebozoan with cellulose in the stalk and spore coat of its fruiting body as well as in the extracellular matrix of the migrating slug. The organism also harbors a number of cellulase genes. One of them, cbhA, was identified as a candidate cellobiohydrolase gene based on the strong homology of its predicted protein product to fungal cellobiohydrolase I (CBHI). Expression of the cbhA was developmentally regulated, with strong expression in the spores of the mature fruiting body. However, a weak but detectable level of expression was observed in the extracellular matrix at the mound - tipped finger stages, in prestalk O cells, and in the slime sheath of the migrating slug - late culminant stages. A null mutant of the cbhA showed almost normal morphology. However, the developmental timing of the mutant was delayed by 2-4 h. When a c-Myc epitope-tagged CbhA was expressed, it was secreted into the culture medium and was able to bind crystalline cellulose. The CbhA-myc protein was glycosylated, as demonstrated by its ability to bind succinyl concanavalin A-agarose. Moreover, conditioned medium from the cbhA-myc (oe) strain displayed 4-methylumbelliferyl beta-D-cellobioside (4-MUC) digesting activity in Zymograms in which conditioned medium was examined via native polyacrylamide gel electrophoresis or spotted on an agar plate containing 4-MUC, one of the substrates of cellobiohydrolase. Taken together, these findings indicate that Dictyostelium CbhA is an orthologue of CBH I that is required for a normal rate of development. PMID- 24240572 TI - Archaeal biology: less means more for Haloferax. PMID- 24240573 TI - VSL#3 probiotics provide protection against acute intestinal ischaemia/reperfusion injury. AB - Acute intestinal ischaemia/reperfusion injury (AII/R) is an adaptive physiologic response during critical illness, involving mesenteric vasoconstriction and hypoperfusion. Prevention of AII/R in high risk patient populations would have a significant impact on morbidity and mortality. The purpose of this study was to investigate the protective effects of VSL#3 probiotic treatment in a murine model of AII/R. Adult 129/SvEv mice were subjected to an experimental AII/R model using superior mesenteric artery occlusion. Animals were pre-treated with either three days or two weeks of VSL#3 probiotics. Local tissue injury markers were assessed by levels of myeloperoxidase and activation of nuclear factor kappa B (NFkB). Systemic and local cytokines, including interleukin (IL)-1beta, IL- 10, TNFalpha, and interferon gamma were measured by ELISA and multiplex fluorescent detection. VSL#3 probiotics reduced local tissue inflammation and injury due to AII/R. A two week course of VSL#3 was more effective than a shorter three-day course. The reduction in local inflammation from the two-week course of VSL#3 is correlated to a significant reduction in levels of active IL-1beta, and tissue levels of myeloperoxidase. Levels of active NFkB were significantly elevated in the vehicle fed AII/R mice, corroborating with tissue inflammation, which were attenuated by VSL#3 administrations. VSL#3 did not cause any systemic inflammation or lung injury. VSL#3 probiotics are effective in reducing local tissue injury from AII/R by down-regulating pro-inflammatory mediators and immune cell recruitment. This study highlights a potential role for VSL#3 in management of patients at high risk for AII/R. PMID- 24240575 TI - A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. AB - Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c) <8.5%] and vitamin D levels less than 20 ng/mL. The participants were randomized into two groups: Placebo (100 mg daily of elemental calcium administered twice a day) or Vitamin D (1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium administered twice a day). We compared outdoor physical activity, glycemic control, homeostasis model of assessment - insulin resistance (HOMA-IR), and parathyroid hormone (PTH), during the 24-week intervention. We analyzed the data of 129 participants (placebo =65, vitamin D =64) who completely followed the protocol. Outdoor physical activity and oral anti-diabetic drugs did not differ between the groups. While there were significant differences in the vitamin D levels (15.6 +/- 7.1 ng/mL vs 30.2 +/- 10.8 ng/mL, P<0.001) and change in PTH levels (1.4 +/- 15.3 pg/mL vs -5.5 +/- 9.8 pg/mL, P=0.003) between the placebo and vitamin D groups, there were no differences in HbA1c (7.27 +/- 0.87% vs 7.40 +/- 0.90%) (P=0.415) and HOMA-IR. Serum calcium and kidney function results showed that the vitamin D supplementation was safe. While vitamin D supplementation is safe and effective in the attainment of vitamin D sufficiency, it had no effect on long-term glycemic control for T2DM in our study. PMID- 24240576 TI - Biased agonism: a novel paradigm in G protein-coupled receptor signaling observed in acquired hypocalciuric hypercalcemia. AB - The classical model of G protein-coupled receptor (GPCR) activation is the two state model, in which the GPCR exists in equilibrium between an active and inactive state. Based on this model, GPCR ligands have been classified as agonists, inverse agonists, or antagonists depending on their actions in shifting this equilibrium. Recently, however, accumulating evidence has indicated that GPCRs may exist in multiple active and inactive conformational states. In this situation, each ligand recognizes and stabilizes a specific conformation of the GPCR, leading to a set of specific biological effects. Based on this new model, a unique agonist or a combination of the usual agonist and an allosteric modulator may enable activation of a specific signaling pathway via a GPCR that activates multiple signals (biased agonism, functional selectivity). The calcium-sensing receptor autoantibody that we have identified in the serum of a patient with acquired hypocalciuric hypercalcemia (AHH) is the first example of a biased allosteric modulator of a GPCR working in a pathophysiological context. Our findings may indicate the presence of physiological allosteric modulators and provide new directions for the future drug development. PMID- 24240577 TI - Inflammatory response after open and laparoscopic Nissen fundoplication in children: a randomized study. AB - PURPOSE: It is assumed that laparoscopic surgery generally induces less inflammatory responses than open surgery. Since few studies have compared immune responses after laparoscopic and open surgery in children, we examined inflammatory markers in children randomized to open (ONF) or laparoscopic Nissen fundoplication (LNF). METHODS: Blood samples were collected prior to surgery (D0), and on postoperative day 1 (D1) and day 2 (D2). Inflammatory markers were measured using a multiplex antibody bead kit. The postoperative levels of inflammatory markers were statistically analyzed using a linear mixed model. A P value <0.05 was considered statistically significant. RESULTS: Twenty-nine patients randomized to ONF or LNF were included. Median age was 3.1 years (range 1.0-14.2) in the ONF group and 4.0 years (range 0.2-14.2) in the LNF group. Plasma levels of the anti-inflammatory cytokine interleukin (IL)-10 were significantly higher in the ONF group than in the LNF group postoperatively (P = 0.04). However, there were no significant differences between the groups in the levels of pro-inflammatory markers tumor necrosis factor-alpha, IL-6, IL-8, monocyte chemoattractant protein-1, white blood cell count, or C-reactive protein. CONCLUSIONS: We did not find that laparoscopy induced a substantially less inflammatory response than laparotomy in children undergoing fundoplication. PMID- 24240578 TI - Gyrate erythema and melanoma-a new clinical association. AB - The authors present the case of a 65-year-old gentleman with a 2.6-mm Breslow thickness melanoma on the lower limb. During his treatment, he underwent several operations including a partial foot amputation. At clinical review, he was noted to have developed an unusual rash. This rash, an annular and gyrate erythema, has never been described before in relation to melanoma, and is sometimes seen in the presence of paraneoplastic processes. Highlighting this new association may enable clinicians to understand and appreciate melanoma better in the future. PMID- 24240579 TI - Smartphones for smarter delivery of mental health programs: a systematic review. AB - BACKGROUND: The rapid growth in the use of mobile phone applications (apps) provides the opportunity to increase access to evidence-based mental health care. OBJECTIVE: Our goal was to systematically review the research evidence supporting the efficacy of mental health apps for mobile devices (such as smartphones and tablets) for all ages. METHODS: A comprehensive literature search (2008-2013) in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, PsycTESTS, Compendex, and Inspec was conducted. We included trials that examined the effects of mental health apps (for depression, anxiety, substance use, sleep disturbances, suicidal behavior, self-harm, psychotic disorders, eating disorders, stress, and gambling) delivered on mobile devices with a pre- to posttest design or compared with a control group. The control group could consist of wait list, treatment-as-usual, or another recognized treatment. RESULTS: In total, 5464 abstracts were identified. Of those, 8 papers describing 5 apps targeting depression, anxiety, and substance abuse met the inclusion criteria. Four apps provided support from a mental health professional. Results showed significant reductions in depression, stress, and substance use. Within-group and between-group intention-to-treat effect sizes ranged from 0.29-2.28 and 0.01-0.48 at posttest and follow-up, respectively. CONCLUSIONS: Mental health apps have the potential to be effective and may significantly improve treatment accessibility. However, the majority of apps that are currently available lack scientific evidence about their efficacy. The public needs to be educated on how to identify the few evidence-based mental health apps available in the public domain to date. Further rigorous research is required to develop and test evidence-based programs. Given the small number of studies and participants included in this review, the high risk of bias, and unknown efficacy of long-term follow-up, current findings should be interpreted with caution, pending replication. Two of the 5 evidence-based mental health apps are currently commercially available in app stores. PMID- 24240580 TI - Nationwide survey of the nature and risk factors of complications in embolization of meningiomas and other intracranial tumors: Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2). AB - INTRODUCTION: Embolization of intracranial tumor is widely performed in Japan, mainly before neurosurgical resection. A retrospective, multicenter, observational study in Japan was conducted to clarify the nature, frequency, and risk factors of complications in intracranial tumor embolization. METHODS: Patients were derived from the Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2). A total of 20,854 patients were enrolled in JR-NET2, of which 1,018 patients (4.88 %) with intracranial tumors underwent embolization. The primary end point was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 (independency) at 30 days. The secondary end point was the occurrence of complications related to the procedures. The risk factors of the occurrence of complications were studied. RESULTS: The proportion of patients with mRS scores <=2 at 30 days after procedure was 91.3 %. Complications occurred in 15 of the 1,012 patients (1.48 %). Multivariate analysis showed that embolization for tumors other than meningioma (OR, 4.626; 95 % CI, 1.347-14.59; p = 0.0105) was significantly associated with the development of complications. CONCLUSION: The frequency of complications after intracranial tumor embolization was relatively low in this large Japanese cohort. Embolization for tumors other than meningioma was the only significant risk factor for the occurrence of complications. PMID- 24240581 TI - Systems biology of cancer biomarker detection. AB - Cancer systems-biology is an ever-growing area of research due to explosion of data; how to mine these data and extract useful information is the problem. To have an insight on carcinogenesis one need to systematically mine several resources, such as databases, microarray and next-generation sequences. This review encompasses management and analysis of cancer data, databases construction and data deposition, whole transcriptome and genome comparison, analysing results from high throughput experiments to uncover cellular pathways and molecular interactions, and the design of effective algorithms to identify potential biomarkers. Recent technical advances such as ChIP-on-chip, ChIP-seq and RNA-seq can be applied to get epigenetic information transformed into a high-throughput endeavour to which systems biology and bioinformatics are making significant inroads. The data from ENCODE and GENCODE projects available through UCSC genome browser can be considered as benchmark for comparison and meta-analysis. A pipeline for integrating next generation sequencing data, microarray data, and putting them together with the existing database is discussed. The understanding of cancer genomics is changing the way we approach cancer diagnosis and treatment. To give a better understanding of utilizing available resources' we have chosen oral cancer to show how and what kind of analysis can be done. This review is a computational genomic primer that provides a bird's eye view of computational and bioinformatics' tools currently available to perform integrated genomic and system biology analyses of several carcinoma. PMID- 24240582 TI - A systematic review of hypermethylation of p16 gene in esophageal cancer. AB - BACKGROUND: Inactivation of cell-cycle regulating gene p16, resulting from epigenetic alteration, is common in the carcinogenesis of human cancers. The aim of this study is to offer a systematic review on the aberrant methylation of p16 gene in esophageal cancer. METHODS: We performed a meta-analysis referring to the guidelines of PRISMA. We searched for articles published from 1996 to 31 May 2012 using PubMed and China National Knowledge Infrastructure (CNKI) database. Additional database including Web of Science and EMBASE were also searched for related articles. The random or fixed effect model was applied to estimate the pooled frequency of DNA methylation based on the heterogeneity analysis. Subgroup analyses were performed according to the histological type, study area, and tumor grade. RESULTS: This meta-analysis included 39 articles related to the methylation studies on p16 gene in cancer tissues and 7 articles using blood samples. The summarized frequency of DNA methylation detected in cancer tissues was 0.53 (95% CI: 0.44-0.61). With the increase of tumor differentiation grades, the frequency of DNA methylation increased accordingly (well differentiated: 0.37; moderately differentiated: 0.61; poorly differentiated: 0.63). We further summarized the methylation of p16 gene detected in patient's peripheral blood samples. The pooled frequency was 0.33 (95% CI: 0.17-0.49), which was lower than that detected in cancer tissues. CONCLUSION: This meta-analysis revealed the elevated frequency of DNA methylation of p16 gene in esophageal cancer, which indicated future potential application of this biomarker in early detection as well as the prognosis of the disease. PMID- 24240583 TI - A novel algorithm for the prediction of prostate cancer in clinically suspected patients. AB - BACKGROUND: Prostate cancer (PCa) represents the most common solid tumor affecting men and its early detection remains the best approach to improve survival rates. The assessment of serum levels of PSA is currently used for PCa screening but the low specificity of the test results in a high number of false positives. Other forms of PSA may be detected in the bloodstream including PSA associated with immunoglobulin M (PSA-IgM) which, alone or combined with PSA, has shown diagnostic accuracy for PCa. OBJECTIVES: The aim of the study is to improve the diagnostic accuracy of PSA-IgM by developing a multivariable model which includes serum biomarkers and routine diagnostic parameters to obtain a predictive index useful in the post-screening clinical practice. PATIENTS AND METHODS: One hundred sixty male patients with clinical suspect of PCa underwent a trans-rectal ultrasound guided first prostate biopsy with a standardized sampling scheme. To generate the model, we assessed the presence of PSA and PSA-IgM complexes in sera of patients and the prostate volume of each patient. A novel predictive probability for PCa (iXip) was obtained combining non-overlapping biomarkers normalized with diagnostic parameters. RESULTS: The study population included 49 patients with PCa diagnosed at biopsy and 111 controls in which prostate biopsy showed the presence of benign prostatic hyperplasia, inflammation, atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia. The iXip values for patients with PCa (mean +/- SD=0.467 +/- 0.160) were significantly higher (p-value < 0.001) than control subjects (mean +/- SD=0.314 +/- 0.098) and the iXip AUC (0.787) was significantly greater (p-value < 0.001) than the AUCs of each biomarker. CONCLUSIONS: iXip shows a significant increase in diagnostic performance compared to PSA and PSA IgM and its post-screening use may facilitate decision-making in recommending for biopsy clinically suspected patients. PMID- 24240584 TI - Positive association between vascular endothelial growth factor (VEGF) -2578 C/A variant and prostate cancer. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) gene is an important angiogenesis regulator related to cancer development and progression. We evaluated the association between -2578 C/A (rs699947) VEGF polymorphism and PCa in Mexican subjects, to contribute to knowledge of VEGF role in genetic epidemiology of prostate cancer (PCa). OBJECTIVE: The aim of this study was to evaluate the association between -2578 C/A VEGF variant and PCa in Mexican population. METHODS: A total of 249 men (77 PCa cases and 172 controls) from the Northwestern region of Mexico were screened for the -2578 C/A VEGF variant. The polymorphism was determined by polymerase chain reaction-based restriction analysis. RESULTS: Genotype frequencies for C/C, C/A, and A/A, were 0.48, 0.49, 0.03 for cases and 0.41, 0.45, 0.14 for controls respectively. Genotype A/A of 2578 VEGF variant reduces the risk of PCa in an 84% among studied population (Odds Ratio 0.16; 95% CI: 0.04-0.71, P=0.007). C/C carriers showed an increased PCa risk of 6.1 times among the study population. CONCLUSIONS: Inheritance of 2578 A/A genotype of VEGF gene may modify PCa susceptibility risk in Mexican population. PMID- 24240585 TI - Gene environment interaction in urinary bladder cancer with special reference to organochlorine pesticide: a case control study. AB - Urinary bladder cancer (UBC) is a common disease worldwide with a higher incidence rate in developed countries. Organochlorine pesticides (OCPs), potent endocrine disrupters, are found to be associated with several cancers such as prostate, breast, bladder, etc. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous environmental toxins including OCPs. The present study was carried out in UBC subjects (n=50) and healthy control subjects (n=50) with an aim to determine the role of GSTM1 and GSTT1 polymorphism and its implication on the OCP detoxification or bioaccumulation which may increase the risk of UBC in humans. This study was also designed to identify the "gene-environment interaction" specifically between gene polymorphism in xenobiotic metabolizing genetic enzyme(s) and blood OCP levels. GSTM1/GSTT1 gene polymorphism was analysed by using multiplex PCR. OCPs levels in whole blood were estimated by Gas chromatography equipped with electron capture detector. The results demonstrated a significant (p< 0.05) increase in frequency of GSTM1^{-}/GSTT1^{-} (null) genotype in UBC cases without interfering the distribution of other GSTT1/GSTM1 genotypes. The blood levels of alpha (alpha), Beta (beta), Gamma (gamma), total - Hexachlorcyclohexane (HCH) and para-para - dichlorodiphenyltrichloroetane (p,p' DDT) were found to be significantly (p< 0.05) high in UBC cases as compared to controls. Multiple regression analysis revealed a significant interaction between beta-HCH and GSTM1^{-} genotype (p< 0.05) as well as in beta HCH and GSTT1^{-} genotype (p< 0.05) respectively. These findings indicate that "gene-environment interaction" may play a key role in increasing the risk for UBC in individuals who are genetically more susceptible due to presence of GSTM1/GSTT1 null deletion during their routine encounter with or exposure to OCPs. PMID- 24240586 TI - Association between HLA-G 3'UTR 14-bp ins/del polymorphism and susceptibility to breast cancer. AB - Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that is highly expressed in cancer pathologies. A 14-bp insertion/deletion polymorphism in exon 8 of the 3' untranslated region (3' UTR) of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. This study aimed to evaluate the association of 14-bp ins/del polymorphism in HLA-G gene and breast cancer in a south-east Iranian population. This study was performed using 236 patients with breast cancer and 203 healthy subjects. We designed a rapid and simple bi directional PCR allele-specific amplification (Bi-PASA) for detection of 14-bp ins/del polymorphism in the HLA-G gene. The results of our study revealed that the prevalence of HLA-G 14-bp homozygote deletion genotype was higher in breast cancer patients than in the control group (OR=2.06, 95%CI=1.23-3.44, P=0.006). The frequency of the Del allele was 56.4% in breast cancer patients and 46.5% in the control group and the difference was statistically significant (OR=1.48, 95%CI=1.13-1.94, P=0.004). Moreover we evaluated the possible correlation of the HLA-G 14-bp ins/del genotypes and clinical characteristics of the patients, but no statistically significant correlation was found (P> 0.05). Our findings, for the first time, suggest that the 14-bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma. Further studies on larger populations with different ethnicities are required to verify our findings. PMID- 24240587 TI - Enhanced expression of EphrinB1 is associated with lymph node metastasis and poor prognosis in breast cancer. AB - BACKGROUND: The Eph family of receptor tyrosine kinases and their ephrin ligands are membrane-bound cell-signaling proteins and they play critical regulatory roles in embryonic development and carcinogenesis. Eph receptors require direct cell to cell interaction for activation and they are divided into EphA and EphB receptor classes, depending on their preferential binding affinity for EphrinA or EphrinB ligands. Eph receptors have been documented in breast cancer, but the Ephrin ligands have not been thoroughly investigated. MATERIALS AND METHODS: We conducted a systematic assessment of EphrinB1 expression in a set of 75 formalin fixed paraffin-embedded breast cancers, using immunohistochemical staining (IHC) with a specific antibody, and we examined the relationship between EphrinB1 expression, histopathological parameters, and the expression of estrogen (ER), progesterone (PR), and HER-2 receptors. RESULTS: High level expression of EphrinB1 is positively associated with lymph node metastasis (P < 0.0001) and with the presence of HER-2 receptor (P=0.041) and it is more often detected in triple-negative breast carcinomas (P=0.038). No relation was apparent between EphrinB1 expression level and other histopathological parameters, but enhanced EphrinB1 expression is associated with shorter overall survival (P=0.015). CONCLUSION: Our analysis demonstrates that EphrinB1 expression is related to the metastasis of breast cancer and its enhanced expression confers a poor prognosis, suggesting that EphrinB1 may be a relevant therapeutic target in breast cancers. PMID- 24240588 TI - Tumorigenesis and tumor progression related gene expression profiles in colorectal cancer. AB - BACKGROUND: To investigate the different gene expression profiles in colorectal cancer (CRC) has important implications in understanding the correlation between candidate genes and clinical histopathological features, as well as in developing prognostic prediction markers. OBJECTIVE: The purpose of this study was to identify the expression profiles of tumorigenesis and tumor progression related genes in Taiwanese CRC patients. METHODS: In this study, we analyze 18 candidate gene expressions of 77 CRC tissues by a GeXP multiplexed assay. RESULTS: The results showed VEGF (71.4%), SOX9 (68.8%), MYC (62.3%), CCND1 (59.7%), TP53 (59.4%), MMP9 (53.3%), and BIRC5 (50.6%) as significantly overexpressed genes in CRC tissues. VEGF was the most highly overexpressed gene. In addition, VEGF was overexpressed in larger tumors (P=0.037, OR=2.981, 95% CI, 1.049-8.477). MMP9 overexpression was correlated to deeper tumor invasion (P=0.001, OR=11.022, 95% CI, 2.281-53.262), and BIRC5 was overexpressed in the presence of perineural invasion (P=0.026, OR=4.250, 95% CI, 1.240-14.562). CONCLUSIONS: The results of this study offered valuable information about the relationship between different gene expressions and clinical pathological features, and these biomarkers represent a potential role for CRC prognosis prediction and establishing therapeutic strategies. PMID- 24240589 TI - Genomic changes in rectal adenocarcinoma associated with liver metastasis. AB - BACKGROUND: At present no objective parameters to identify the risk of liver metastasis after surgery have been established in rectal cancer. OBJECTIVE: To identify the chromosomal aberrations that are correlated with liver metastasis of rectal cancer. METHODS: Primary tumor tissues of rectal carcinoma were analyzed by array-based comparative genomic hybridization (array-CGH). Genomic aberrations were identified by Genomic Workbench and MD-SeeGH. RESULTS: The most frequent gains in rectal cancer were at 20q11.21-q13.33, 8q11.21-q24.3, 13q12.11-q14.2 and losses in 5q13.2, 8p23.3-p22, 17p13.3-p13.2 and 18q11.2-q23. Seven amplifications at 6p21.1, 8q24.21, 8q24.3, 13q13.2 and 20q13.2-q13.32 and nine homozygous deletions at 1q31.3, 4q12-q13.1, 4q32.3-q33, 5q13.2, 8p23.2, 8q11.23, 16p13.2, 19p13.11 and 19q13.41 were identified. Both frequency plot comparison and SAM (Significance analysis of microarray) methods indicated that losses at 1p35.3, 4p14, 14q23.1-q32.11 and 18p11.32-p11.21 were more frequent in patients without liver metastasis. CONCLUSIONS: These liver metastasis associated genomic changes may be useful to reveal the mechanism of metastasis and identify candidate biomarkers. PMID- 24240590 TI - Myristoylated alanine-rich C-kinase substrate as a prognostic biomarker in human primary lung squamous cell carcinoma. AB - To identify novel biomarkers for the diagnosis and prognosis of human primary lung squamous cell carcinoma (SCC), we compared the spectrum of proteins expressed in SCC and in the adjacent non-cancer tissue, using QSTAR Elite liquid chromatography with tandem mass spectrometry (LC-MS/MS), coupled with iTRAQ technology. We identified 410 proteins differentially expressed in more than 75% of patients, and validated the expression of candidate target proteins by immunohistochemistry. Based on the results of LC-MS/MS, Ingenuity Pathway Analysis and immunohistochemical analyses, myristoylated alanine-rich C-kinase substrate (MARCKS) (upregulated 2.28-fold, p< 0.005) was selected as a potential biomarker of human lung SCC. In order to evaluate the association between patient prognosis and the expression of candidate biomarkers, univariate survival analysis was performed with disease-specific survival curves according to the Kaplan-Meier method, and differences in survival were assessed with the log-rank test. Immunohistochemical evaluation of MARCKS in 99 patients with lung SCC revealed a significant association between positive expression and poor prognosis compared with patients with negative expression (log-rank test; p=0.024). These results indicate that MARCKS may represent a potential biomarker for the prognosis of primary lung SCC. PMID- 24240591 TI - Expression of PI3K, PTEN and Akt in small intestinal adenocarcinoma detected by quantum dots-based immunofluorescence technology. AB - BACKGROUND: Small intestinal adenocarcinoma (SIA) is often diagnosed at an advanced stage due to its rarity and nonspecific clinical manifestations. Abnormal activation of the PI3K/Akt pathway may lead to various diseases including cancer. In this study, we explored the relationship between those pathways and SIA. OBJECTIVE: To investigate the expression of PI3K, phospho-Akt (p-Akt) and PTEN in SIA to evaluate their clinical significance. METHODS: Expression of PI3K, p-Akt and PTEN biomarkers were examined by quantum dots-based immunofluorescence histochemistry (QDs-IHC) and traditional immunohistochemistry (IHC). There are 53 SIA samples, 11 non-cancer tissue samples and 11 normal small intestine tissues. RESULTS: The positive frequencies of PI3K and p-Akt expression were significantly higher in the SIA group (77.4%, 41/53 and 77.4%, 41/53, respectively) than that in the non-cancer group (36.4%, 4/11 and 27.3, 3/11, respectively) and normal small intestine tissue group (36.4%, 4/11 and 18.2, 2/11, respectively). However, the difference of the positive rates of PTEN expression in three groups did not reach a statistical difference (P=0.761). The IHC results were in concordance with the QDs-IHC. CONCLUSIONS: These observations support that PI3K/Akt pathway is highly activated in SIA, which may implicate therapeutic targeting of the PI3K/Akt signaling pathway for its treatment. PMID- 24240592 TI - What's new in Shock? December 2013. PMID- 24240598 TI - A multimodal emotion detection system during human-robot interaction. AB - In this paper, a multimodal user-emotion detection system for social robots is presented. This system is intended to be used during human-robot interaction, and it is integrated as part of the overall interaction system of the robot: the Robotics Dialog System (RDS). Two modes are used to detect emotions: the voice and face expression analysis. In order to analyze the voice of the user, a new component has been developed: Gender and Emotion Voice Analysis (GEVA), which is written using the Chuck language. For emotion detection in facial expressions, the system, Gender and Emotion Facial Analysis (GEFA), has been also developed. This last system integrates two third-party solutions: Sophisticated High-speed Object Recognition Engine (SHORE) and Computer Expression Recognition Toolbox (CERT). Once these new components (GEVA and GEFA) give their results, a decision rule is applied in order to combine the information given by both of them. The result of this rule, the detected emotion, is integrated into the dialog system through communicative acts. Hence, each communicative act gives, among other things, the detected emotion of the user to the RDS so it can adapt its strategy in order to get a greater satisfaction degree during the human-robot dialog. Each of the new components, GEVA and GEFA, can also be used individually. Moreover, they are integrated with the robotic control platform ROS (Robot Operating System). Several experiments with real users were performed to determine the accuracy of each component and to set the final decision rule. The results obtained from applying this decision rule in these experiments show a high success rate in automatic user emotion recognition, improving the results given by the two information channels (audio and visual) separately. PMID- 24240593 TI - Lactobacillus rhamnosus GG improves outcome in experimental pseudomonas aeruginosa pneumonia: potential role of regulatory T cells. AB - INTRODUCTION: Recent clinical trials show Lactobacillus rhamnosus GG (LGG) administration in critical illness has the potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of LGG mediated benefit following illness and injury remain elusive. OBJECTIVE: The aim of this study was to determine the effect of LGG treatment on survival and lung injury in a mouse model of Pseudomonas aeruginosa-induced pneumonia. As increased T regulatory (Treg) cell numbers have been shown to improve outcome in experimental pneumonia, we examined the potential role of Treg cells in probiotic mediated benefit. METHODS: FVB/N mice were subjected to intratracheal injection of either P. aeruginosa or saline and received LGG or vehicle immediately before procedure. T regulatory cell responses in the lung were evaluated by polymerase chain reaction, Western blotting, and flow cytometry. RESULTS: Mice treated with LGG had significantly improved 7-day survival (P < 0.01) compared with saline treated control pneumonia mice (55% LGG vs. 14% control). The survival advantage was associated with reduced bacterial counts in bronchoalveolar lavage and with decreased markers of the systemic inflammatory response and improved lung pathology in the probiotic group. Probiotic treatment influenced immune response in the lungs of mice with pneumonia as demonstrated by increased levels of Treg cell marker Foxp3. CONCLUSIONS: These data demonstrate that early administration of LGG improves outcome following P. aeruginosa-induced pneumonia. An effect of LGG on Treg cells may play a role in this protection. PMID- 24240599 TI - Data management for the internet of things: design primitives and solution. AB - The Internet of Things (IoT) is a networking paradigm where interconnected, smart objects continuously generate data and transmit it over the Internet. Much of the IoT initiatives are geared towards manufacturing low-cost and energy-efficient hardware for these objects, as well as the communication technologies that provide objects interconnectivity. However, the solutions to manage and utilize the massive volume of data produced by these objects are yet to mature. Traditional database management solutions fall short in satisfying the sophisticated application needs of an IoT network that has a truly global-scale. Current solutions for IoT data management address partial aspects of the IoT environment with special focus on sensor networks. In this paper, we survey the data management solutions that are proposed for IoT or subsystems of the IoT. We highlight the distinctive design primitives that we believe should be addressed in an IoT data management solution, and discuss how they are approached by the proposed solutions. We finally propose a data management framework for IoT that takes into consideration the discussed design elements and acts as a seed to a comprehensive IoT data management solution. The framework we propose adapts a federated, data- and sources-centric approach to link the diverse Things with their abundance of data to the potential applications and services that are envisioned for IoT. PMID- 24240600 TI - Incorporation of conjugated linoleic acid isomers into porcine erythrocytes. AB - PURPOSE: The aim of the current study was to determine the incorporation of cis (c) 9, trans (t) 11-conjugated linoleic acid (CLA) and t10, c12-CLA into porcine erythrocytes-both isomers were supplemented in equal proportions. METHODS: The study group consisted of 16 piglets randomly assigned into experimental and control group. For the period of 5 weeks, the piglets from the experimental group were receiving a 1.2% CLA supplement while the controls were supplemented with the same amount of sunflower oil. For the remaining 7 weeks, the piglets were fed without a supplement. Blood samples to evaluate incorporation of CLA into erythrocyte membranes were taken from all animals on weekly basis. RESULTS: Compared to t10, c12-CLA isomer, proportion of c9, t11-CLA isomer in the membrane of erythrocytes was higher for the whole time of the study period. After 4 weeks of feeding, it approaches the plateau. The peak value for both isomers was measured at the end of week 5, with a value of 3.24 g c9, t11-CLA/100 g of fatty acids and a 1.09 g t10, c12-CLA/100 g of fatty acids (p < 0.0001). After cessation of supplementation, the proportion of both isomers gradually decreased to be almost completely washed out-in 7 weeks. CONCLUSIONS: During supplementation with equivalent amounts of CLA isomers, their proportion in membranes of porcine erythrocytes increases with time, with higher proportion of c9, t11-CLA. CLA isomers probably differently incorporate into different cell membranes at different species which could explain its various biological functions. PMID- 24240601 TI - Higher volume of ventral striatum and right prefrontal cortex in pathological gambling. AB - Functional neuroimaging studies have implicated an involvement of the prefrontal cortex and mesolimbic reward system (i.e., ventral striatum) in pathological gambling (PG). However, there is a lack of studies focusing on structural changes in frontostriatal brain regions in adult subjects with PG. In order to study differences in local grey matter volume, 20 male subjects with PG and 21 matched controls underwent structural magnetic resonance imaging. Structural brain data were analysed via voxel-based morphometry with a focus on prefrontal areas and ventral striatum. By comparing grey matter volumes in brain regions highly relevant for brain functional changes in PG, the present study found a higher volume in right ventral striatum and right prefrontal cortex by means of voxel wise morphometry in PG subjects as compared to controls. Our findings demonstrate local grey matter changes in brain areas that have previously been associated with functional changes in PG. Hypertrophy in the prefrontal cortex might be an adaptation at least partly induced by the higher grey matter volume in the ventral striatum and may help to increase cognitive control over gambling impulses. Future research should explore the relationship between functional and structural alterations as well as the course of changes in PG. PMID- 24240602 TI - Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study. AB - We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2 BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD. PMID- 24240604 TI - [Therapy of hepatocellular carcinoma]. AB - Today, hepatocellular carcinoma (HCC) represents the leading cause of death in patients with liver cirrhosis; in most western countries the incidence is also expected to increase further. Due to insufficient surveillance of patients at risk, most cases are diagnosed in an intermediate to advanced stage, leading together with the underlying liver cirrhosis-to limited therapeutic options and a dismal prognosis. Therefore, classification according to stage and interdisciplinary treatment decisions in experienced centers are of paramount importance to provide an individualized treatment plan when considering potentially curative (resection, liver transplantation, local ablation) and palliative (transarterial approaches, sorafenib) treatment options. There is hope that the prognosis of patients with HCC can be improved in the near future by better prevention, stringent surveillance, multimodality treatment approaches, and an expansion of personalized medicine. PMID- 24240605 TI - [A 79-year-old patient with severe bleeding after colon surgery and normal global coagulation parameters]. AB - We report the case of a 79-year-old Caucasian male, who underwent anterior resection of the rectum for treatment of a colorectal carcinoma. Two days after the surgery, the patient had mild but persistent haemorrhage from all drains and around the wounds which eventually required blood transfusion (18 units of erythrocyte concentrate and 8 units of fresh-frozen plasma). Endoscopy revealed no surgical bleeding source, and standard coagulation tests were inconspicuous. Based on suspicion of factor XIII deficiency, the patient was treated with factor XIII concentrate (1250 I.U. injections twice daily), starting on day 4 of bleeding. The bleeding stopped after the second dose of factor XIII. Laboratory testing retrospectively revealed the lack of factor XIII (43 % at the first day of dosing). Factor XIII concentrate was administered for 10 days. Withdrawal of factor XIII after 9 days of treatment led to a bleeding recurrence. After resuming treatment for one more day, the therapy could be stopped without further bleeding. Thus, factor XIII deficiency should be considered in patients with unexplained postoperative bleeding and appropriate diagnostic measures be taken early. In cases of medical emergency, probative administration of factor XIII may be justified. PMID- 24240607 TI - Non-interventional study evaluating efficacy and tolerability of rifaximin for treatment of uncomplicated diverticular disease. AB - Patients with symptomatic uncomplicated diverticular disease represent a spectrum of patients who report recurrent abdominal symptoms, however are lacking substantial colonic inflammation in contrast to patients with acute diverticulitis. This non-interventional study investigated the efficacy and tolerability of rifaximin, a broad-spectrum poorly absorbable antibiotic, in cyclic treatment of these patients. Adult patients with uncomplicated diverticular disease in care of physicians in private practice intended to be treated with rifaximin were included. Patients with acute diverticulitis and symptoms suggestive of more severe intestinal inflammation were excluded. Data of 1,003 patients treated in cycles of 7-10 days per month over a period of 3 months were evaluated. In total, 75 % of patients had more than three episodes of symptoms in the last year before inclusion in the study. However, two-third of patients did not receive any treatment before. Over the 3-month treatment period with rifaximin, all assessed symptoms of diverticular disease, such as abdominal pain, diarrhoea and flatulence, improved significantly. There was an overall good compliance to the scheme of cyclic drug administration of rifaximin. During the study, 24 adverse events in 20 patients were recorded, of which 6 adverse events showed a causal relationship to the use of rifaximin (0.6 %). We conclude that cyclic rifaximin shows good clinical efficacy and tolerability in patients with symptomatic uncomplicated diverticular disease treated in a routine private practice outpatient setting. PMID- 24240608 TI - Patient-reported outcome reference values for patients after kidney transplantation. AB - BACKGROUND: Patient-reported outcomes (PROs) are important in managing kidney transplant patients. Although, there are many instruments available to assess PROs, such as health-related quality of life (HRQOL), they are rarely collected in routine nephrology practices. Therefore, the aim of this study was the determination of reference values for physical and psychosocial symptom burden in kidney transplant patients. METHODS: Patients with a history of kidney transplantation being in aftercare at a nephrological outpatient unit (n = 120) were consecutively recruited, and a computer-based PRO assessment was used to assess their HRQOL reference values. It covered a broad range of clinically relevant physical and psychological symptoms, adherence to immunosuppressants, and disease-specific quality of life. On an average, PROs were assessed 2.9 times per patient, 351 times in total. RESULTS: For PRO monitoring in kidney transplant patients, we consider the 10th/90th percentile as being of particular clinical relevance, as patients exceeding these scores are likely to be in need of additional care. CONCLUSIONS: With continuously rising survival rates after kidney transplantation, HRQOL of long-term transplant patients becomes increasingly important, and it is generally accepted that HRQOL improves after successful kidney transplantation. We used a computerized PRO monitoring to determine HRQOL reference values for outpatient kidney transplant patients. Routine PRO monitoring may facilitate the identification of patient issues relevant to treatment, and may contribute to improved symptom and side-effect management. Future studies providing detailed PRO values for stratified patient samples are needed. PMID- 24240609 TI - Gastrointestinal bleeding associated with dabigatran in a patient with panhypopituitarism. PMID- 24240611 TI - Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial. AB - IMPORTANCE: A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials. OBJECTIVE: To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions (mechanical CPR), compared with manual cardiopulmonary resuscitation (manual CPR), according to guidelines, would improve 4-hour survival. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial of 2589 patients with out of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. INTERVENTIONS: Patients were randomized to receive either mechanical chest compressions (LUCAS Chest Compression System, Physio-Control/Jolife AB) combined with defibrillation during ongoing compressions (n = 1300) or to manual CPR according to guidelines (n = 1289). MAIN OUTCOMES AND MEASURES: Four-hour survival, with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category (CPC) score. A CPC score of 1 or 2 was classified as a good outcome. RESULTS: Four-hour survival was achieved in 307 patients (23.6%) with mechanical CPR and 305 (23.7%) with manual CPR (risk difference, -0.05%; 95% CI, -3.3% to 3.2%; P > .99). Survival with a CPC score of 1 or 2 occurred in 98 (7.5%) vs 82 (6.4%) (risk difference, 1.18%; 95% CI, -0.78% to 3.1%) at intensive care unit discharge, in 108 (8.3%) vs 100 (7.8%) (risk difference, 0.55%; 95% CI, -1.5% to 2.6%) at hospital discharge, in 105 (8.1%) vs 94 (7.3%) (risk difference, 0.78%; 95% CI, -1.3% to 2.8%) at 1 month, and in 110 (8.5%) vs 98 (7.6%) (risk difference, 0.86%; 95% CI, -1.2% to 3.0%) at 6 months with mechanical CPR and manual CPR, respectively. Among patients surviving at 6 months, 99% in the mechanical CPR group and 94% in the manual CPR group had CPC scores of 1 or 2. CONCLUSIONS AND RELEVANCE: Among adults with out-of-hospital cardiac arrest, there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline-adherent manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. In clinical practice, mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609778. PMID- 24240612 TI - Biased Brownian ratcheting leads to pre-mRNA remodeling and capture prior to first-step splicing. AB - The spliceosome is a dynamic ribonucleoprotein (RNP) machine that catalyzes the removal of introns during the two transesterification steps of eukaryotic pre mRNA splicing. Here we used single-molecule fluorescence resonance energy transfer to monitor the distance of the 5' splice site (5' SS) and branch point (BP) of pre-mRNA in affinity-purified spliceosomes stalled by a mutation in the DExD/H-box helicase Prp2 immediately before the first splicing step. Addition of recombinant Prp2 together with NTP and protein cofactor Spp2 rearranges the spliceosome-substrate complex to reversibly explore conformations with proximal 5' SS and BP that accommodate chemistry. Addition of Cwc25, a small heat-stable splicing factor, then strongly biases this equilibrium toward the proximal conformation, promoting efficient first-step splicing. The spliceosome thus functions as a biased Brownian ratchet machine where a helicase unlocks thermal fluctuations subsequently rectified by a cofactor 'pawl', a principle possibly widespread among the many helicase-driven RNPs. PMID- 24240613 TI - JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks. AB - Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA-damage response (DDR) pathway. JMJD1C was stabilized by interaction with RNF8, was recruited to DSBs, and was required for local ubiquitylations and recruitment of RAP80-BRCA1 but not 53BP1. JMJD1C bound to RNF8 and MDC1, and demethylated MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitylation and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1. Furthermore, JMJD1C restricted formation of RAD51 repair foci, and JMJD1C depletion caused resistance to ionizing radiation and PARP inhibitors, phenotypes relevant to aberrant loss of JMJD1C in subsets of breast carcinomas. These findings identify JMJD1C as a DDR component, with implications for genome-integrity maintenance, tumorigenesis and cancer treatment. PMID- 24240614 TI - Repriming of DNA synthesis at stalled replication forks by human PrimPol. AB - DNA replication forks that collapse during the process of genomic duplication lead to double-strand breaks and constitute a threat to genomic stability. The risk of fork collapse is higher in the presence of replication inhibitors or after UV irradiation, which introduces specific modifications in the structure of DNA. In these cases, fork progression may be facilitated by error-prone translesion synthesis (TLS) DNA polymerases. Alternatively, the replisome may skip the damaged DNA, leaving an unreplicated gap to be repaired after replication. This mechanism strictly requires a priming event downstream of the lesion. Here we show that PrimPol, a new human primase and TLS polymerase, uses its primase activity to mediate uninterrupted fork progression after UV irradiation and to reinitiate DNA synthesis after dNTP depletion. As an enzyme involved in tolerance to DNA damage, PrimPol might become a target for cancer therapy. PMID- 24240616 TI - [Researcher of the month]. PMID- 24240615 TI - Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43. AB - TDP-43 encodes an alternative-splicing regulator with tandem RNA-recognition motifs (RRMs). The protein regulates cystic fibrosis transmembrane regulator (CFTR) exon 9 splicing through binding to long UG-rich RNA sequences and is found in cytoplasmic inclusions of several neurodegenerative diseases. We solved the solution structure of the TDP-43 RRMs in complex with UG-rich RNA. Ten nucleotides are bound by both RRMs, and six are recognized sequence specifically. Among these, a central G interacts with both RRMs and stabilizes a new tandem RRM arrangement. Mutations that eliminate recognition of this key nucleotide or crucial inter-RRM interactions disrupt RNA binding and TDP-43-dependent splicing regulation. In contrast, point mutations that affect base-specific recognition in either RRM have weaker effects. Our findings reveal not only how TDP-43 recognizes UG repeats but also how RNA binding-dependent inter-RRM interactions are crucial for TDP-43 function. PMID- 24240617 TI - Directed use of the internet for health information by patients with chronic kidney disease: prospective cohort study. AB - BACKGROUND: Health information technology has become common in the care of patients with chronic diseases; however, there are few such applications employed in kidney disease. OBJECTIVE: The aim of the study was to evaluate the use of a website providing disease-specific safety information by patients with predialysis chronic kidney disease. METHODS: As part of the Safe Kidney Care (SKC) study, an educational website was designed to provide information on safety concerns in chronic kidney disease. Phase I study participants were provided a medical alert accessory with a unique ID number, the Safe Kidney Care website, and an in-person tutorial on the use of the Internet and accessing the SKC website at baseline. Participants were asked to visit the website and enter their unique ID as frequently as they desired over the next 365 days or until their annual follow-up visit, whichever occurred first. Participants' visits and dwell times on specific safety modules were tracked using embedded webpage PHP scripts linked to a MySQL database, enabling the collection of website usage statistics. RESULTS: Of 108 Phase I participants, 28.7% (31/108) visited the website from 1-6 times during the observation period (median follow-up 365 days). Median access time was 7 minutes per visit (range <1-46) and 13 minutes per person (range <1 123). The three most frequently visited pages were "Renal function calculator", "Pills to avoid", and "Foods to avoid". High school education and frequent Internet use were significantly associated with website entry (P=.02 and P=.03, respectively). CONCLUSIONS: Preliminary results show general interest in a Web based platform designed to improve patient safety in chronic kidney disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT01407367; http://clinicaltrials.gov/show/NCT01407367 (Archived by WebCite at http://www.webcitation.org/6KvxFKA6M). PMID- 24240619 TI - Prophylactic gastrectomy in a 16-year-old. AB - We performed a total gastrectomy in a 16-year-old asymptomatic CDH1 gene mutation carrier in whom two prior gastroscopies with biopsies were normal. The patient's mother died aged 39 years and her aunt died aged 21 years of gastric cancer. A germline CDH1 mutation (associated with hereditary diffuse gastric cancer) was initially identified in her mother at diagnosis and was later identified by predictive testing in this patient. Our patient is the youngest CDH1 carrier to date to have a prophylactic gastrectomy, and is several years below the age at which existing guidelines recommend consideration of gastrectomy. Multiple foci of early-stage carcinoma were found in her gastrectomy specimen. Given the family history of advanced gastric cancer in the late second decade, the unpredictable time course to development of advanced gastric cancer, and the futility of gastroscopic surveillance, we recommend consideration of prophylactic gastrectomy in adolescent asymptomatic CDH1 mutation carriers on an individual basis. PMID- 24240620 TI - The extensor pollicis longus-loop-knot (ELK) procedure for dynamic balance of the paralyzed thumb interphalangeal joint. AB - Hyperflexion of the thumb interphalangeal (IP) joint interferes significantly with pinching between the thumb and the index finger in a paralyzed hand. The extensor pollicis longus-loop-knot (ELK) procedure was used successfully in 7 tetraplegic patients to balance the IP joint between strong restored flexor function and lacking or weak antagonism of the thumb extensors. A V-shaped incision was made over the extensor hood at the level of the IP joint, the extensor pollicis longus (EPL) tendon was elevated, a loop was formed, secured by sutures, and then turned proximally onto the EPL tendon itself and fixed on both sides. The operation reliably limited the maximum range of IP flexion at 20 to 30 degrees from neutral. Postoperative problems did not occur. The ELK procedure is easy and quick and secures the optimal setting of IP flexion with limited flexibility, which is advantageous compared with rigid bony arthrodesis. It also avoids certain disadvantages of the commonly used flexor pollicis longus split tenodesis and is therefore a valuable alternative for the correction of Froment's sign due to intrinsic or extrinsic paralysis of the thumb. PMID- 24240621 TI - Application of an antibiotic intramedullary nail in the management of a large metacarpal bone defect. AB - Contaminated wounds and infected nonunions of the hand are not amenable to primary internal fixation and grafting. Antibiotic-impregnated cement intramedullary nails have been used in the lower extremity in the treatment of these fractures but have not been described in the hand. This technique combines the advantages of local antibiotic delivery with the mechanical stability afforded by an intramedullary nail. We describe an alternative technique for the management of skeletal defects in a contaminated wound bed in the hand using readily available operating room equipment. The antibiotic-impregnated cement intramedullary nail can be placed temporarily until definitive internal fixation and grafting occur. PMID- 24240622 TI - Dorsal spanning plate fixation for distal radius fractures. AB - In polytrauma patients, the presence of a multifragmentary distal radius fracture poses a challenge with respect to early mobilization. Dorsal spanning plate fixation is an alternative choice for these patients for providing definitive operative fixation of the distal radius fracture and for providing a construct to allow weight-bearing through the injured wrist for rehabilitative purposes. In this article, we describe the operative technique to place a dorsal spanning plate and provide a retrospective review of outcomes in polytrauma patients. PMID- 24240623 TI - Minimally invasive tension band wiring technique for olecranon fractures. AB - Some types of implants, such as plates, screws, wires, and nails, have been used for open reduction and internal fixation of olecranon fractures. A >= 10 cm longitudinal incision is used for open reduction and internal fixation of olecranon fractures. According to previous studies, tension band wiring is a popular method that gives good results. However, back out of the wires after the surgery is one of the main postoperative complications. Moreover, if the Kirschner wires are inserted through the anterior ulnar cortex, they may impinge on the radial neck, supinator muscle, or biceps tendon. Herein, we describe the minimally invasive tension band wiring technique using Ring-Pin. This technique can be performed through a 2 cm incision. Small skin incisions are advantageous from an esthetic viewpoint. Ring-Pin was fixed by using a dedicated cable wire that does not back out unless the cable wire breaks or slips out of the dedicated metallic clamp. As the pins are placed in intramedullary canal, this technique does not lead to postoperative complications that may occur after transcortical fixation by conventional tension band wiring. Minimally invasive tension band wiring is one of the useful options for the treatment of olecranon fractures with some advantages. PMID- 24240624 TI - A systematic method of arthroscopic testing of extrinsic carpal ligaments: implication in carpal stability. AB - Several biomechanical studies have shown that the scapholunate and lunotriquetral ligaments are not the only stabilizers of the proximal carpal row. However, no study has yet analyzed the spectrum of ligamentous lesions in vivo, leading to instability. We describe an arthroscopic technique for evaluating the extrinsic carpal ligaments. The testing relies on visualization and palpation of different ligaments. Their integrity is assessed with a 4-stage scale. Radiocarpal arthroscopy enables assessment of the following ligaments: the radiocarpal part of the radio-scapho-capitate, the long radiolunate, the short radiolunate, the ulnolunate, the ulnotriquetral, and the dorsal radiocarpal. Midcarpal arthroscopy enables assessment of the mid part of the radio-scapho-capitate, the triquetrocapitate, the scaphotrapezial, and the dorsal intercarpal. Above assessment is proposed in addition to assessing the articular cartilage, scapholunate, and lunotriquetral ligaments. This method allows a precise arthroscopic assessment of the extrinsic ligaments of the wrist. It could give an important help in the understanding of carpal instability. PMID- 24240625 TI - Post-traumatic malunion of the distal radial intra-articular fractures treated with autologous costal osteochondral grafts and bioabsorbable plates. AB - Intra-articular distal radial fractures with partial bone loss at the wrist were reconstructed using osteochondral grafts in 2 patients who were followed up for at least 18 months. Both patients experienced posttraumatic arthrosis of the wrist joint. The materials of the intra-articular fixation were bioabsorbable plates and screws. Reconstruction of a partially destroyed articular surface using a costal osteochondral graft is reliable and allows filling and resurfacing an articular cartilage void. PMID- 24240626 TI - Strategies for reducing regional variation in the use of surgery: a systematic review. AB - OBJECTIVE: To review the literature evaluating the effect of practice guidelines and decision aids on use of surgery and regional variation. BACKGROUND: The use of surgical procedures varies widely across geographic regions. Although practice guidelines and decision aids have been promoted for reducing variation, their true effectiveness is uncertain. METHODS: Studies evaluating the influence of clinical practice guidelines or consensus statements, shared decision making and decision aids, or provider feedback of comparative utilization, on rates of surgical procedures were identified through literature searches of Ovid MEDLINE, EMBASE, and Web of Science. RESULTS: A total of 1946 studies were identified and 27 were included in the final review. Of the 12 studies evaluating implementation of guidelines, 6 reported a significant effect. Those examining overall population-based rates had mixed effects, but all studies evaluating procedure choice described at least a small increase in use of recommended therapy. Three of 5 studies examining the effect of guidelines on regional variation reported a significant reduction after dissemination. Of the 15 studies examining decision aids, 5 revealed significant effects. Many studies of decision aids reported decreases in population-based procedure rates. Nearly all studies evaluating the impact of decision aids on procedure choice reported increases in rates of less invasive procedures. Only one study of decision aids assessed changes in regional variation and found mixed results. CONCLUSIONS: Both practice guidelines and decision aids have been proven effective in many clinical contexts. Expanding the clinical scope of these tools and eliminating barriers to implementation will be essential to further efforts directed toward reducing regional variation in the use of surgery. PMID- 24240627 TI - ENERgized vessel sealing systems versus CONventional hemostasis techniques in thyroid surgery--the ENERCON systematic review and network meta-analysis. AB - PURPOSE: Energized vessel-sealing systems have been proposed to save operation time and reduce post-operative complications. The aim of the present systematic review was to compare operation time and postoperative morbidity for ultrasonic and electrothermal bipolar-activated devices with conventional hemostasis techniques and with each other in open thyroidectomy. METHODS: A systematic literature search (MEDLINE, Cochrane Library, EMBASE and ISI Web of Science) was performed to identify randomised controlled trials (RCTs) comparing conventional hemostasis techniques, ultrasonic devices (Harmonic(r) scalpel) and/or electrothermal bipolar-activated vessel sealing systems (Ligasure(r)) during open thyroidectomy. For the primary endpoint (operation time), a network meta-analysis with Bayesian random effects model was performed. Pairwise meta-analyses with random effects were calculated for primary and secondary endpoints. RESULTS: One hundred sixteen publications were evaluated for eligibility; 35 RCTs (4,061 patients) were included. There was considerable methodological and clinical heterogeneity of included trials. The Harmonic scalpel significantly reduced operation time compared with conventional techniques (22.26 min, 22.7 min in the inconsistency model). The use of Ligasure significantly reduced operation time in total thyroidectomy (13.84 min in the consistency model, 12.18 min in the inconsistency model). In direct comparison, operations with the Harmonic scalpel were faster than with Ligasure (8.42 min in the consistency model, 2.45 min in the inconsistency model). The rates of recurrent nerve palsy and postoperative hypocalcaemia did not significantly differ in the intervention groups. CONCLUSIONS: This meta-analysis shows superiority of ultrasonic devices in terms of operation time compared with conventional hemostasis techniques in thyroid surgery, with no detriment to safety outcomes. PMID- 24240628 TI - Overexpression of p62/SQSTM1 promotes the degradations of abnormally accumulated PrP mutants in cytoplasm and relieves the associated cytotoxicities via autophagy lysosome-dependent way. AB - The protein of p62/sequestosome 1 (SQSTM1), a key cargo adaptor protein involved in autophagy-lysosome degradation, exhibits inclusion bodies structure in cytoplasm and plays a protective role in some models of neurodegenerative diseases. Some PrP mutants, such as PrP-CYTO and PrP-PG14, also form cytosolic inclusion bodies and trigger neuronal apoptosis either in cultured cells or in transgenic mice. Here, we demonstrated that the cellular p62/SQSTM1 incorporated into the inclusion bodies formed by expressing the abnormal PrP mutants, PrP-CYTO and PrP-PG14, in human embryonic kidney 293 cells. Overexpression of p62/SQSTM1 efficiently relieved the cytosolic aggregations and cell apoptosis induced by the abnormal PrPs. Autophagy-lysosome inhibitors instead of proteasome inhibitor sufficiently blocked the p62/SQSTM1-mediated degradations of abnormal PrPs. Overexpression of p62/SQSTM1 did not alter the levels of light chain 3 (LC3) in the cells expressing various PrPs. However, more complexes of p62/SQSTM1 with LC3 were detected in the cells expressing the misfolded PrPs. These data imply that p62/SQSTM1 plays an important role in the homeostasis of abnormal PrPs via autophagy-lysosome-dependent way. PMID- 24240630 TI - Reference values for cardiorespiratory fitness and incidence of type 2 diabetes. AB - BACKGROUND: In "Physical Activity Reference for Health Promotion 2013" the Japan Ministry of Health, Labour and Welfare publication gives reference values for cardiorespiratory fitness (CRF) required for good health. We examined the associations between the CRF reference values and incidence of type 2 diabetes. METHODS: This prospective cohort study enrolled 4633 nondiabetic Japanese men aged 20 to 39 years at baseline. CRF was measured using the cycle ergometer test, and maximal oxygen uptake was estimated. On the basis of the CRF reference value, participants were classified into 2 groups: those with values less than the reference value (under-RV) and those with values equal to or greater than reference value (over-RV). Hazard ratios (HRs) and 95% CIs for incident type 2 diabetes were estimated using a Cox proportional hazards model. RESULTS: A total of 266 participants developed type 2 diabetes during the 14 years of follow-up. As compared with the under-RV group, the over-RV group had a significantly lower multivariable-adjusted HR for type 2 diabetes (HR 0.67; 95% CI, 0.51-0.89). In receiver operating characteristic analysis, the optimal CRF cut-off value for predicting incident type 2 diabetes was 10.8 metabolic equivalents (sensitivity, 0.64; specificity, 0.64), which was close to the CRF reference value of 11.0 metabolic equivalents. CONCLUSIONS: The reference CRF value appears to be reasonably valid for prevention of type 2 diabetes, especially among Japanese men younger than 40 years. Development of type 2 diabetes can be prevented by maintaining a CRF level above the reference value. PMID- 24240629 TI - Information processing speed and 8-year mortality among community-dwelling elderly Japanese. AB - BACKGROUND: Cognitive function is an important contributor to health among elderly adults. One reliable measure of cognitive functioning is information processing speed, which can predict incident dementia and is longitudinally related to the incidence of functional dependence. Few studies have examined the association between information processing speed and mortality. This 8-year prospective cohort study design with mortality surveillance examined the longitudinal relationship between information processing speed and all-cause mortality among community-dwelling elderly Japanese. METHODS: A total of 440 men and 371 women aged 70 years or older participated in this study. The Digit Symbol Substitution Test (DSST) was used to assess information processing speed. DSST score was used as an independent variable, and age, sex, education level, depressive symptoms, chronic disease, sensory deficit, instrumental activities of daily living, walking speed, and cognitive impairment were used as covariates. RESULTS: During the follow-up period, 182 participants (133 men and 49 women) died. A multivariate Cox proportional hazards model showed that lower DSST score was associated with increased risk of mortality (hazard ratio [HR] = 1.62, 95% CI = 0.97-2.72; HR = 1.73, 95% CI = 1.05-2.87; and HR = 2.55, 95% CI = 1.51-4.29, for the third, second, and first quartiles of DSST score, respectively). CONCLUSIONS: Slower information processing speed was associated with shorter survival among elderly Japanese. PMID- 24240631 TI - Diagnostic accuracy of the E-plate serum antibody test kit in detecting Helicobacter pylori infection among Japanese children. AB - BACKGROUND: A number of noninvasive diagnostic tests are available to detect Helicobacter pylori infection. Data on serologic testing of children are lacking, however, and thus it remains unclear whether the serology cutoff points used for adults are appropriate for children. METHODS: Serum and stool samples were obtained from 73 children who visited 5 hospitals in Japan between March 1993 and December 2009. Analysis of stool samples was carried out using an H pylori stool antigen enzyme-linked immunosorbent assay (HpSA ELISA), and serum antibodies to H pylori were examined using an antibody determination kit (E-Plate Eiken H pylori antibody). The validity of the serologic test was evaluated based on its sensitivity, specificity, and receiver operating characteristics curve. RESULTS: Of the 73 children included in this study, 34 were HpSA-positive and 39 were negative. Among the 34 HpSA-positive patients, 32 were IgG-positive and 2 were IgG-negative. Of the 39 patients who were HpSA-negative, 38 were IgG-negative and 1 was IgG-positive. The sensitivity, specificity, and positive likelihood ratio for IgG antibody testing were 91.2%, 97.4%, and 35.6, respectively, based on the recommended adult cutoff point of 10 U/ml. Among children, use of cutoff points in the range of 7 to 9 U/ml yielded optimal values for sensitivity and specificity, as well as a positive likelihood ratio. CONCLUSIONS: The performance of the E-plate anti-H pylori IgG antibody test was comparable to that of the stool antigen test and is therefore suitable for epidemiologic studies of H pylori infection in large samples. PMID- 24240632 TI - Risk factors for community-based reports of gastrointestinal, respiratory, and dermal symptoms: findings from a cohort study in Australia. AB - BACKGROUND: Although gastrointestinal (GI), respiratory, and dermal symptoms are common, few studies have conducted concurrent and comparative prospective analyses of risk factors for these 3 morbidity outcomes. METHODS: We used data from a community-based randomized controlled trial among 277 South Australian families to analyze GI (diarrhea, vomiting), respiratory (sore throat, runny nose, cough) and dermal (rash, generalized itch, dermal infection) symptoms. RESULTS: Log-binomial regression analysis revealed similar risks of GI (adjusted risk ratio [RR], 1.65; 95% CI, 1.05-2.58) and respiratory (RR, 1.68; 95% CI, 1.31 2.15) symptoms among childcare/kindergarten attendees. Swimming in public pools/spas in the current or previous week was associated with all 3 symptom complexes, conferring similar risk for each (RR for GI: 1.33; 95% CI, 0.99-1.77; respiratory: 1.20; 95% CI, 1.04-1.38; dermal: 1.41; 95% CI, 1.08-1.85). Pet ownership was not associated with symptoms. Household clustering of GI and respiratory symptoms was common, and clustering of respiratory symptoms correlated with number of individuals per household. CONCLUSIONS: This simultaneous examination of risk factors for 3 health outcomes yielded new comparative data that are useful for developing prevention strategies. PMID- 24240633 TI - Delayed ipsilateral parenchymal hemorrhage following treatment of intracranial aneurysms with flow diverter. AB - INTRODUCTION: The use of flow diverters (FDs) has shown promising results, particularly in the treatment of large or complex intracranial aneurysms. However, some complications can occur both during and after FD treatment, including delayed ipsilateral parenchymal hemorrhage (DIPH). The clinical presentation, etiopathogeny, and management of this complication are not well understood. We report a series of four patients with DIPH and discuss the potential mechanisms and modalities of treatment. METHODS: Four patients treated with FDs and presenting with DIPH were diagnosed in two different centers. Clinical and imaging data were reviewed before and after the procedure. Characteristics of the intraparenchymal hematomas, the modalities of treatment, and clinical course were analyzed. RESULTS: Intraparenchymal hemorrhage occurred 1 to 4 days after aneurysm treatment with FDs. All hemorrhages were situated in the ipsilateral hemisphere and were anatomically remote from the treated aneurysm. The four patients were treated with emergency surgery (hematoma evacuation). All patients had a favorable clinical outcome (mRS = 1) at midterm evaluation. Follow-up imaging showed good permeability of the FD in all subjects and complete aneurysm occlusion in all patients. CONCLUSION: From the literature review, DIPH appears to be more frequent than delayed aneurysm rupture and may be a cause of increasing concern for the use of flow diverters. However, the mechanisms of DIPH are not completely understood. Surgical evacuation of the hematoma seems to be feasible with acceptable safety and good clinical outcomes. PMID- 24240634 TI - Determination and method validation of metamitron in soil by RP-HPLC. AB - A simple, rapid and economical method was developed and validated for the determination of metamitron using UV detector with RP-HPLC. Study of metamitron in soil was carried out. The compound was extracted from soil by methanol and clean-up was done on C-18 SPE column. Recovery ranged from 90.75 % to 94.05 % within 0.1-2.0 MUg g(-1) and RSD 1.80 %. Retention time was 3.8 min and limit of detection and limit of quantification were 0.001 and 0.008 MUg g(-1). The results indicated that the reported method could meet the requirement for the analysis of metamitron in trace amounts. PMID- 24240635 TI - A cross-sectional study of antenatal depression and associated factors in Malawi. AB - Depression, and disabling levels of mixed depressive, anxious and somatic symptoms, termed common mental disorder, occurring in the perinatal period are an important health problem in low- and middle-income countries. In this cross sectional study, pregnant women were recruited from a district hospital antenatal clinic in Malawi. Symptoms of depression and anxiety, and non-specific somatic symptoms commonly associated with distress, were measured using validated local versions of the Self Reporting Questionnaire (SRQ). In a sub-sample, Diagnostic Statistical Manual (DSM)-IV diagnoses of major and minor depressive disorders were made using the Structured Clinical Interview for DSM-IV. Maternal socio demographic and health variables were measured, and associations with SRQ score and depression diagnosis were determined. Of 599 eligible women, 583 were included in the analysis. The adjusted weighted prevalence of current major depressive episode and current major or minor depressive episode were 10.7 % (95 % CI 6.9-14.5 %) and 21.1 % (95 % CI 15.5-26.6 %), respectively. On multivariate analysis, SRQ score was significantly associated with lower perceived social support, experience of intimate partner violence, having had a complication in a previous delivery, higher maternal mid-upper arm circumference and more years of schooling. Major depressive episode was associated with lower perceived social support and experience of intimate partner violence. This study demonstrates that antenatal depression/CMD is common in Malawi and is associated with factors that may be amenable to psychosocial interventions. PMID- 24240636 TI - Efficacy of systemically oriented psychotherapies in the treatment of perinatal depression: a meta-analysis. AB - The objective of this meta-analysis was to examine the efficacy of systemically oriented psychotherapy treatments for depression in pregnancy and the postpartum. Specifically, this synthesis examined standardized mean differences between pre- and posttest and treatment-control conditions in depression symptom reduction among 24 individual interpersonal psychotherapy or relational psychotherapy studies completed between 1997 and 2013. Analyses assessed heterogeneity, potential moderators, and publication bias. Random-effects analyses revealed a large, positive average effect size [Formula: see text] for psychotherapy treatments among one-group, pre-post-studies and a medium, positive average effect [Formula: see text] when treatments were compared with control groups. Mixed-effects meta-ANOVAs indicated that treatment type, participant depression severity, and method of depression assessment were significant moderators such that effect sizes were larger among individual interpersonal psychotherapy studies, clinical samples, and studies that included an independent evaluation of depression. However, relational treatments and studies with nonclinical samples were less represented in the literature, and still demonstrated small to medium positive effects. Meta-regressions revealed that effects were largest when treatments were delivered with adherence fidelity checks and over more sessions. Based on funnel plots and Egger tests, there was evidence of publication bias in this analysis; however, the effects were distributed fairly symmetrically about the mean given the relatively small number of available studies. Findings have implications for continued examination of systemically oriented psychotherapy treatments for depression in pregnancy and the postpartum. PMID- 24240637 TI - 10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology. AB - We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10 min delayed recall scores <=4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were >=19 (the median), 3MS 10-min delayed recall scores <=4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID- 24240638 TI - Connecting health-related quality of life and mental health in dementia caregivers from Colombia, South America. AB - Research in Caucasian populations has begun to examine the broad associations between physical and mental health in dementia caregivers. However, the examination of this relationship in Latin America is largely absent from the literature despite the fact that the region will see a major increase in dementia cases over the next 20 years. The current study examined the associations between health-related quality of life (HRQOL) and mental health in 90 dementia caregivers from Colombia, South America. A canonical correlation found that higher caregiver HRQOL was related to better mental health, as expected. Caregivers with high vitality and low role limitations due to physical problems tended to have low depression and high satisfaction with life. Follow-up multiple regressions found that caregiver role limitations due to physical problems was uniquely associated with satisfaction with life, whereas vitality, role limitations due to physical problems, and pain were uniquely associated with burden (although the pain effect was likely error due to a suppressor effect). Additionally, vitality and social functioning were uniquely negatively related to depression. Because of the extremely high overlap between these two sets of variables, dementia interventions are needed in Latin America that target both caregiver mental and physical health, as both likely operate in unison and influence each other. PMID- 24240639 TI - Identification of N-terminally truncated pyroglutamate amyloid-beta in cholesterol-enriched diet-fed rabbit and AD brain. AB - The main amyloid-beta peptide (Abeta) variants detected in the human brain are Abeta1-40 and Abeta1-42; however, a significant proportion of Abeta in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AbetaN3(pE), Abeta peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Abeta deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Abeta accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD. In the present study, we have demonstrated for the first time the presence of AbetaN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AbetaN3(pE) immunoreactivity in all postmortem AD brain samples studied. We believe that our results are potentially important for evaluation of novel therapeutic molecules/strategies targeting Abeta peptides in a suitable non transgenic animal model. PMID- 24240641 TI - Randomized comparison of a silicone tape and a paper tape for gentleness in healthy children. AB - PURPOSE: To compare the relative gentleness of a silicone tape to a paper tape in healthy infants and children. DESIGN: A randomized, grader-blinded, comparative study. SUBJECTS AND SETTING: The sample group comprised 24 healthy infants and children 9.1 to 46.7 months of age (mean +/- SEM, 34.0 +/- 2.21). The study was conducted at a dermatological research facility (cyberDERM, Inc) located in Broomall, Pennsylvania. All volunteers were recruited from the surrounding community. METHODS: Tapes measuring 1 * 1.5 inches were randomly applied to the left and right intrascapular regions of the upper back. Tapes were removed in a standardized fashion after 24 hours. The primary study outcome, gentleness, was based on visual assessments of skin damage, discomfort, and quantification of keratin removal. Four-point scales were used to assess skin damage, and a 10 point Faces, Legs, Activity, Cry, and Consolability instrument was used to assess discomfort. Secondary assessments included hair removal, tape edge-lift assessments, and parent preference for either tape. RESULTS: There was a significantly lower mean +/- SEM erythema response for the silicone tape (0.93 +/ 0.14 vs 1.35 +/- 0.11, P = .0129) than for the paper tape. No measurable epidermal stripping occurred with the silicone tape compared to a mean +/- SEM response of 0.29 +/- 0.11 for the paper tape (P = .0039). Discomfort was significantly lower (P = .0002) for the silicone tape as compared to the paper tape (Faces, Legs, Activity, Cry, and Consolability score mean difference from baseline 0.5 vs 3.3, P = .0002). Keratin removal was significantly less with the silicone as compared to paper tape (8.7 +/- 0.5 MUg/mL vs 15.2 +/- 1.3 MUg/mL, P < .0001). Few hairs were removed with either tape. There was significantly less (P < .0001) edge-lift with the paper tape than the silicone tape; no statistically significant differences in parent preferences for silicone versus paper tapes were measured (P = .3359). CONCLUSIONS: Gentleness assessments favored the silicone tape compared to a paper tape and warrant further clinical investigation in the neonatal intensive care unit. PMID- 24240640 TI - Structural diversity of Alzheimer's disease amyloid-beta dimers and their role in oligomerization and fibril formation. AB - Alzheimer's disease (AD) is associated with the formation of toxic amyloid-beta (Abeta)42 oligomers, and recent evidence supports a role for Abeta dimers as building blocks for oligomers. Molecular dynamics simulation studies have identified clans for the dominant conformations of Abeta42 forming dimers; however, it is unclear if a larger spectrum of dimers is involved and which set(s) of dimers might evolve to oligomers verse fibrils. Therefore, for this study we generated multiple structural conformations of Abeta42, using explicit all-atom molecular dynamics, and then clustering the different structures based on key conformational similarities. Those matching a selection threshold were then used to model a process of oligomerization. Remarkably, we showed a greater diversity in Abeta dimers than previously described. Depending on the clan family, different types of Abeta dimers were obtained. While some had the tendency to evolve into oligomeric rings, others formed fibrils of diverse characteristics. Then we selected the dimers that would evolve to membranephilic annular oligomers. Nearly one third of the 28 evaluated annular oligomers had the dimer interfaces between the neighboring Abeta42 monomers with possible salt bridges between the residue K28 from one side and either residue E22 or D23 on the other. Based on these results, key amino acids were identified for point mutations that either enhanced or suppressed the formation and toxicity of oligomer rings. Our studies suggest a greater diversity of Abeta dimers. Understanding the structure of Abeta dimers might be important for the rationale design of small molecules that block formation of toxic oligomers. PMID- 24240642 TI - Potential degradation of swainsonine by intracellular enzymes of Arthrobacter sp. HW08. AB - Swainsonine (SW) is a toxin produced by locoweeds and harmful to the livestock industry. Degrading SW by Arthrobacter sp. HW08 was demonstrated as a promising way to deal with SW poisoning. However, it is unknown which part of the subcellular enzymes in Arthrobacter sp. HW08 is responsible for biodegrading SW and whether the metabolites are atoxic. In this study, intracellular and extracellular enzymes of Arthrobacter sp. HW08 were isolated and their enzyme activity was evaluated. The metabolites were fed to mice, and physiological and histological properties of the treated mice were investigated. The results showed that only intracellular enzyme of Arthrobacter sp. HW08 (IEHW08) could degrade SW efficiently. Compared with mice in SW treatment group, mice in SW + IEHW08 treatment group (1) increased their body weights; (2) showed higher number of platelets and lower number of white blood cells; (3) decreased the levels of creatinine, urea nitrogen, alanine transaminase and aspartate aminotransferase in serum; (4) reduced the number of vacuolated cells in cerebellum, liver and kidney. All these data demonstrate that IEHW08 was potentially safe for mice, while keeping the capacity of degrading SW. This study indicates a possible application of IEHW08 as an additive in the livestock industry to protect animals from SW poisoning. PMID- 24240645 TI - The sexual health care needs after colorectal cancer: the view of patients, partners, and health care professionals. AB - PURPOSE: Sexual dysfunction among patients with colorectal cancer is frequently reported. Studies examining patients' sexual health care needs are rare. We examined the sexual health care needs after colorectal cancer treatment according to patients, partners, and health care professionals (HCPs). Factors that impede or facilitate the quality of this care were identified. METHOD: Participants were recruited from three Dutch hospitals: St. Elisabeth, TweeSteden, and Catharina hospitals. Patients (n = 21), partners (n = 9), and 10 HCPs participated in eight focus groups. RESULTS: It is important to regularly evaluate and manage sexual issues. This does not always occur. Almost all participants reported a lack of knowledge and feelings of embarrassment or inappropriateness as barriers to discuss sexuality. HCPs reported stereotypical assumptions regarding the need for care based on age, sex, and partner status. The HCPs debated on whose responsibility it is that sexuality is discussed with patients. Factors within the organization, such as insufficient re-discussion of sexuality during (long term) follow-up and unsatisfactory (knowledge of the) referral system impeded sexual health care. The HCPs could facilitate adequate sexual health care by providing patient-tailored information and permission to discuss sex, normalizing sexual issues, and establishing an adequate referral system. It is up to the patients and partners to demarcate the extent of sexual health care needed. CONCLUSIONS: Our findings illustrate the need for patient-tailored sexual health care and the complexity of providing/receiving this care. An adequate referral system and training are needed to help HCPs engage in providing satisfactory sexual health care. PMID- 24240644 TI - Factors associated with intention to use internet-based testing for sexually transmitted infections among men who have sex with men. AB - BACKGROUND: Internet-based testing programs are being increasingly used to reduce testing barriers for individuals at higher risk of infection, yet the population impact and potential for exacerbation of existing health inequities of these programs are not well understood. OBJECTIVE: We used a large online sample of men who have sex with men (MSM) in Canada to measure acceptability of Internet-based testing and perceived advantages and disadvantages of this testing approach. METHODS: We asked participants of the 2011/2012 Sex Now Survey (a serial online survey of gay and bisexual men in Canada) whether they intended to use Internet based testing and their perceived benefits and disadvantages of use. We examined whether intention to use was associated with explanatory variables spanning (A) sociodemographics, (B) Internet and technology usage, (C) sexually transmitted infections (STI)/ human immunodeficiency virus (HIV) and risk, and (D) health care access and testing, using multivariable logistic regression (variable selection using Bayesian information criterion). RESULTS: Overall, intention to use was high (5678/7938, 71.53%) among participants with little variation by participant characteristics. In our final model, we retained the variables related to (B) Internet and technology usage: use of Internet to cruise for sex partners (adjusted odds ratio [AOR] 1.46, 95% CI 1.25-1.70), use of Internet to search for sexual health information (AOR 1.36, 95% CI 1.23-1.51), and mobile phone usage (AOR 1.19, 95% 1.13-1.24). We also retained the variables for (D) health care access and testing: not "out" to primary care provider (AOR 1.24, 95% CI 1.10-1.41), delayed/avoided testing due to privacy concerns (AOR 1.77, 95% CI 1.49-2.11), and delayed/avoided testing due to access issues (AOR 1.65, 95% CI 1.40-1.95). Finally, we retained the variable being HIV positive (AOR 0.56, 95% CI 0.46-0.68) or HIV status unknown (AOR 0.89, 95% CI 0.77-1.01), age <30 years (AOR 1.41, 95% CI 1.22-1.62), and identifying as bisexual (AOR 1.18, 95% CI 1.04 1.34) or straight/other (AOR 0.67, 95% CI 0.50-0.90). The greatest perceived benefits of Internet-based testing were privacy (2249/8388, 26.81%), general convenience (1701/8388, 20.28%), and being able to test at any time (1048/8388, 12.49%). The greatest perceived drawbacks were the inability to see a doctor or nurse (1507/8388, 17.97%), wanting to talk to someone about results (1430/8388, 17.97%), not wanting online results (1084/8388, 12.92%), and low trust (973/8388, 11.60%). CONCLUSIONS: The high and wide-ranging intention to use that we observed suggests Internet-based testing has the potential to reach into all subgroups of MSM and may be particularly appealing to those facing current barriers to accessing STI/HIV testing and who are more comfortable with technology. These findings will be used to inform the promotion and further evaluation of an Internet-based testing program currently under development in British Columbia, Canada. PMID- 24240646 TI - Association between supportive care interventions and patient self-reported depression among advanced cancer outpatients. AB - PURPOSE: Advanced cancer patients often experience moderate to severe physical and emotional distress. One of the main components of emotional distress is depression. The objective of this study was to examine the association between supportive care interventions and patient self-reported depression (PSRD) among advanced cancer outpatients. METHODS: We included consecutive patients seen in the outpatient Supportive Care Center between February 2008 and February 2010 with at least one follow-up visit. We used the Edmonton Symptom Assessment Scale (ESAS) to assess their symptom intensity. Clinical improvement of PSRD was defined as an improvement of at least 30% between the initial visit and the first follow-up. We used logistic regression models to assess possible predictors of improvement in PSRD. RESULTS: We included 444 patients with a median age of 59 years (Q1-Q3; 51-65). The most common type of cancer was gastrointestinal (98, 22%). Out of the 444 patients, 160 (36%) reported moderate/severe depression at baseline (ESAS item score >= 4/10). Higher baseline depression intensity was significantly associated to anxiety (r = 0.568, p = 0.046), total symptom distress score (TSDS; r = 0.550, p < 0.001) and personal history of depression (r = 0.242, p = 0.001). Of the 160 patients, 90 (56%) with moderate/severe PSRD at baseline showed a significant improvement at the follow-up visit (p = 0.038). Improvement in anxiety, sedation, and feeling of well-being were associated with higher depression improvement (OR 7.93, CI 3.74-16.80 and OR 2.44, CI 1.09-5.46, respectively). CONCLUSIONS: More than 50% patients with moderate/severe PSRD significantly improved after one single supportive/palliative care consultation. Improvements of anxiety and sedation were independently associated with PSRD improvement. PMID- 24240647 TI - A pilot phase II RCT of a home-based exercise intervention for survivors of AML. AB - BACKGROUND: Fatigue is the most common and disabling symptom affecting quality of life (QOL) and daily function in patients who have completed treatment for acute myeloid leukemia (AML). Although trials in patients with various solid tumors have reported improved fatigue and QOL following exercise interventions, there have been no studies in AML patients post treatment. METHODS: Forty patients aged >= 40 years who had completed treatment for AML were enrolled in a 12-week randomized phase II exercise intervention to determine feasibility (recruitment, retention, and adherence), efficacy, and safety of the intervention. Patients assigned to the exercise group received an individualized, moderate-intensity, 12 week home-based exercise program with weekly telephone support from a certified exercise physiologist. QOL, fatigue, and fitness outcomes were measured at baseline, 6 weeks, and 12 weeks. Between-group differences in 12-week change scores were calculated using linear regression adjusting for age and baseline function. RESULTS: Recruitment and retention rates were 38% and 91%, respectively. Adherence was low at 28%. Analyses did not suggest statistically significant or clinically important benefits in QOL, fatigue, or physical fitness with the intervention. The level of adherence did not appear to impact outcomes. There were no adverse events. CONCLUSION: A home-based exercise program for post treatment AML patients age 40 years or older can be safely delivered with reasonable recruitment and high retention. However, feasibility was hampered by low adherence. Further research and program modification are needed to better understand and overcome barriers to exercise delivery and adherence in AML survivors. PMID- 24240648 TI - A comparison of physical activity correlates across breast, prostate and colorectal cancer survivors in Nova Scotia, Canada. AB - PURPOSE: The purpose of this study was to compare the medical, demographic and social cognitive correlates of physical activity (PA) in breast (BCS), prostate (PCS) and colorectal (CRCS) cancer survivors. METHODS: A stratified random sample of 2062 BC, PC and CRC survivors diagnosed between 2003 and 2011 was identified by the Nova Scotia Cancer Registry (NSCR) and mailed a questionnaire assessing PA, social-cognitive constructs from the theory of planned behaviour (TPB), and demographic and medical variables. Structural equation modelling was used to conduct path analyses of the TPB within each cancer survivor group and an invariance analysis was used to compare the TPB across groups. RESULTS: A total of 741 completed surveys were analysed. Overall, 42% of cancer survivors were meeting PA guidelines with no differences among the cancer sites. Treatment related variables were strong correlates of PA in PC survivors but not for BC or CRC. Body mass index was strongly associated with PA in BC survivors but not PC or CRC. Path analyses within each cancer survivor group showed that intention was significantly associated with PA for CRCS only; planning was significantly associated with PA for BCS and PCS only; and perceived behavioural control (PBC) was significantly associated with PA for PCS only. For intention, PBC and instrumental attitude (IA) were significant correlates in all three cancer survivor groups whereas affective attitude (AA) was significant for BCS and CRCS only; and descriptive norm (DN) was significant for PCS and CRCS only. Invariance analyses revealed significantly stronger relationships for (a) intention to planning for BCS compared to PCS, (b) affective attitude to intention for CRCS compared to PCS, and (c) planning to PA for PCS compared to CRCS. CONCLUSIONS: Although BC, PC, and CRC survivors have similar levels of PA, the correlates of their PA may differ. These findings may inform cancer site-specific interventions to promote PA in cancer survivors. PMID- 24240649 TI - Effectiveness of palonosetron for preventing delayed chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy in patients with gastrointestinal cancer. AB - PURPOSE: Patients with gastrointestinal cancer who were receiving moderately emetogenic chemotherapy (MEC) were switched from granisetron, a first-generation 5-hydroxytryptamine-3 receptor antagonist, to palonosetron at our hospital. In the present study, we compared effectiveness before and after switching antiemetic treatment. METHODS: Among patients who were receiving MEC for gastrointestinal cancer, we prospectively observed 46 patients given granisetron and 46 given palonosetron. To allow adverse reactions to be graded in accordance with the Common Terminology Criteria for Adverse Events, version 4.0, a questionnaire designed at our hospital was used to compare the occurrence of delayed nausea and vomiting between patients who received granisetron (GRA group) and those who received palonosetron (PAL group). RESULTS: The incidence of delayed nausea was significantly lower in the PAL group (8.7%, 4/46; p < 0.01) than in the GRA group (37%, 17/46). Delayed vomiting developed in five patients (10.9%) in the GRA group, but did not occur in the PAL group. On the basis of the results of multivariate analysis, young age, female gender, and the use of granisetron were significant risk factors for delayed nausea. CONCLUSION: Our survey showed that palonosetron effectively controls delayed nausea caused by MEC for gastrointestinal cancer. PMID- 24240650 TI - Dynamics of the risk of smoking-induced lung cancer: a compartmental hidden Markov model for longitudinal analysis. AB - BACKGROUND: To account for the dynamic aspects of carcinogenesis, we propose a compartmental hidden Markov model in which each person is healthy, asymptomatically affected, diagnosed, or deceased. Our model is illustrated using the example of smoking-induced lung cancer. METHODS: The model was fitted on a case-control study nested in the European Prospective Investigation into Cancer and Nutrition study, including 757 incident cases and 1524 matched controls. Estimation was done through a Markov Chain Monte Carlo algorithm, and simulations based on the posterior estimates of the parameters were used to provide measures of model fit. We performed sensitivity analyses to assess robustness of our findings. RESULTS: After adjusting for its impact on exposure duration, age was not found to independently drive the risk of lung carcinogenesis, whereas age at starting smoking in ever-smokers and time since cessation in former smokers were found to be influential. Our data did not support an age-dependent time to diagnosis. The estimated time between onset of malignancy and clinical diagnosis ranged from 2 to 4 years. Our approach yielded good performance in reconstructing individual trajectories in both cases (sensitivity >90%) and controls (sensitivity >80%). CONCLUSION: Our compartmental model enabled us to identify time-varying predictors of risk and provided us with insights into the dynamics of smoking-induced lung carcinogenesis. Its flexible and general formulation enables the future incorporation of disease states, as measured by intermediate markers, into the modeling of the natural history of cancer, suggesting a large range of applications in chronic disease epidemiology. PMID- 24240651 TI - Prospective cohort studies of newly marketed medications: using covariate data to inform the design of large-scale studies. AB - BACKGROUND: Nonrandomized safety and effectiveness studies are often initiated immediately after the approval of a new medication, but patients prescribed the new medication during this period may be substantially different from those receiving an existing comparator treatment. Restricting the study to comparable patients after data have been collected is inefficient in prospective studies with primary collection of outcomes. METHODS: We discuss design and methods for evaluating covariate data to assess the comparability of treatment groups, identify patient subgroups that are not comparable, and decide when to transition to a large-scale comparative study. We demonstrate methods in an example study comparing Cox-2 inhibitors during their postmarketing period (1999-2005) with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). RESULTS: Graphical checks of propensity score distributions in each treatment group showed substantial problems with overlap in the initial cohorts. In the first half of 1999, >40% of patients were in the region of nonoverlap on the propensity score, and across the study period this fraction never dropped below 10% (the a priori decision threshold for transitioning to the large-scale study). After restricting to patients with no prior NSAID use, <1% of patients were in the region of nonoverlap, indicating that a large-scale study could be initiated in this subgroup and few patients would need to be trimmed from analysis. CONCLUSIONS: A sequential study design that uses pilot data to evaluate treatment selection can guide the efficient design of large-scale outcome studies with primary data collection by focusing on comparable patients. PMID- 24240652 TI - PM2.5 exposure and birth outcomes: use of satellite- and monitor-based data. AB - BACKGROUND: Air pollution may be related to adverse birth outcomes. Exposure information from land-based monitoring stations often suffers from limited spatial coverage. Satellite data offer an alternative data source for exposure assessment. METHODS: We used birth certificate data for births in Connecticut and Massachusetts, United States (2000-2006). Gestational exposure to PM2.5 was estimated from US Environmental Protection Agency monitoring data and from satellite data. Satellite data were processed and modeled by using two methods denoted satellite (1) and satellite (2)-before exposure assessment. Regression models related PM2.5 exposure to birth outcomes while controlling for several confounders. Birth outcomes were mean birth weight at term birth, low birth weight at term (<2500 g), small for gestational age (SGA, <10th percentile for gestational age and sex), and preterm birth (<37 weeks). RESULTS: Overall, the exposure assessment method modified the magnitude of the effect estimates of PM2.5 on birth outcomes. Change in birth weight per interquartile range (2.41 MUg/m) increase in PM2.5 was -6 g (95% confidence interval = -8 to -5), -16 g ( 21 to -11), and -19 g (-23 to -15), using the monitor, satellite (1), and satellite (2) methods, respectively. Adjusted odds ratios, based on the same three exposure methods, for term low birth weight were 1.01 (0.98-1.04), 1.06 (0.97-1.16), and 1.08 (1.01-1.16); for SGA, 1.03 (1.01-1.04), 1.06 (1.03-1.10), and 1.08 (1.04-1.11); and for preterm birth, 1.00 (0.99-1.02), 0.98 (0.94-1.03), and 0.99 (0.95-1.03). CONCLUSIONS: Under exposure assessment methods, we found associations between PM2.5 exposure and adverse birth outcomes particularly for birth weight among term births and for SGA. These results add to the growing concerns that air pollution adversely affects infant health and suggest that analysis of health consequences based on satellite-based exposure assessment can provide additional useful information. PMID- 24240653 TI - Nested case-control studies in cohorts with competing events. AB - In nested case-control studies, incidence density sampling is the time-dependent matching procedure to approximate hazard ratios. The cumulative incidence function can also be estimated if information from the full cohort is used. In the presence of competing events, however, the cumulative incidence function depends on the hazard of the disease of interest and on the competing events hazard. Using hospital-acquired infection as an example (full cohort), we propose a sampling method for nested case-control studies to estimate subdistribution hazard ratios. With further information on the full cohort, the cumulative incidence function for the event of interest can then be estimated as well. PMID- 24240654 TI - Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. AB - BACKGROUND: Independent studies report association of autism spectrum disorder with air pollution exposure and a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. Toxicological data find altered brain Met expression in mice after prenatal exposure to a model air pollutant. Our objective was to investigate whether air pollution exposure and MET rs1858830 genotype interact to alter the risk of autism spectrum disorder. METHODS: We studied 252 cases of autism spectrum disorder and 156 typically developing controls from the Childhood Autism Risk from Genetics and the Environment Study. Air pollution exposure was assigned for local traffic-related sources and regional sources (particulate matter, nitrogen dioxide, and ozone). MET genotype was determined by direct resequencing. RESULTS: Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures. There was evidence of multiplicative interaction between NO2 and MET CC genotype (P= 0.03). CONCLUSIONS: MET rs1858830 CC genotype and air pollutant exposure may interact to increase the risk of autism spectrum disorder. PMID- 24240655 TI - Net reclassification indices for evaluating risk prediction instruments: a critical review. AB - Net reclassification indices have recently become popular statistics for measuring the prediction increment of new biomarkers. We review the various types of net reclassification indices and their correct interpretations. We evaluate the advantages and disadvantages of quantifying the prediction increment with these indices. For predefined risk categories, we relate net reclassification indices to existing measures of the prediction increment. We also consider statistical methodology for constructing confidence intervals for net reclassification indices and evaluate the merits of hypothesis testing based on such indices. We recommend that investigators using net reclassification indices should report them separately for events (cases) and nonevents (controls). When there are two risk categories, the components of net reclassification indices are the same as the changes in the true- and false-positive rates. We advocate the use of true- and false-positive rates and suggest it is more useful for investigators to retain the existing, descriptive terms. When there are three or more risk categories, we recommend against net reclassification indices because they do not adequately account for clinically important differences in shifts among risk categories. The category-free net reclassification index is a new descriptive device designed to avoid predefined risk categories. However, it experiences many of the same problems as other measures such as the area under the receiver operating characteristic curve. In addition, the category-free index can mislead investigators by overstating the incremental value of a biomarker, even in independent validation data. When investigators want to test a null hypothesis of no prediction increment, the well-established tests for coefficients in the regression model are superior to the net reclassification index. If investigators want to use net reclassification indices, confidence intervals should be calculated using bootstrap methods rather than published variance formulas. The preferred single-number summary of the prediction increment is the improvement in net benefit. PMID- 24240656 TI - Estimating the per-exposure effect of infectious disease interventions. AB - The average effect of an infectious disease intervention (eg, a vaccine) varies across populations with different degrees of exposure to the pathogen. As a result, many investigators favor a per-exposure effect measure that is considered independent of the population level of exposure and that can be used in simulations to estimate the total disease burden averted by an intervention across different populations. However, while per-exposure effects are frequently estimated, the quantity of interest is often poorly defined, and assumptions in its calculation are typically left implicit. In this article, we build upon work by Halloran and Struchiner (Epidemiology. 1995;6:142-151) to develop a formal definition of the per-exposure effect and discuss conditions necessary for its unbiased estimation. With greater care paid to the parameterization of transmission models, their results can be better understood and can thereby be of greater value to decision-makers. PMID- 24240657 TI - Asthma morbidity and ambient air pollution: effect modification by residential traffic-related air pollution. AB - BACKGROUND: Ambient air pollution has been associated with asthma-related hospital admissions and emergency department visits (hospital encounters). We hypothesized that higher individual exposure to residential traffic-related air pollutants would enhance these associations. METHODS: We studied 11,390 asthma related hospital encounters among 7492 subjects 0-18 years of age living in Orange County, California. Ambient exposures were measured at regional air monitoring stations. Seasonal average traffic-related exposures (PM2.5, ultrafine particles, NOx, and CO) were estimated near subjects' geocoded residences for 6 month warm and cool seasonal periods, using dispersion models based on local traffic within 500 m radii. Associations were tested in case-crossover conditional logistic regression models adjusted for temperature and humidity. We assessed effect modification by seasonal residential traffic-related air pollution exposures above and below median dispersion-modeled exposures. Secondary analyses considered effect modification by traffic exposures within race/ethnicity and insurance group strata. RESULTS: Asthma morbidity was positively associated with daily ambient O3 and PM2.5 in warm seasons and with CO, NOx, and PM2.5 in cool seasons. Associations with CO, NOx, and PM2.5 were stronger among subjects living at residences with above-median traffic-related exposures, especially in cool seasons. Secondary analyses showed no consistent differences in association, and 95% confidence intervals were wide, indicating a lack of precision for estimating these highly stratified associations. CONCLUSIONS: Associations of asthma with ambient air pollution were enhanced among subjects living in homes with high traffic-related air pollution. This may be because of increased susceptibility (greater asthma severity) or increased vulnerability (meteorologic amplification of local vs. correlated ambient exposures). PMID- 24240658 TI - Prognostic ROC curves: a method for representing the overall discriminative capacity of binary markers with right-censored time-to-event endpoints. AB - Survival curves are a popular tool for representing the association between a binary marker and the risk of an event. The separation between the survival curves in patients with a positive marker (high-risk group) and a negative marker (low-risk group) reflects the prognostic ability of the marker. In this article, we propose an alternative graphical approach to represent the discriminative capacity of the marker-a receiver operating characteristic (ROC) curve, tentatively named prognostic ROC curve-obtained by plotting 1 minus the survival in the high-risk group against 1 minus the survival in the low-risk group. The area under the curve corresponds to the probability that a patient in the low risk group has a longer lifetime than a patient in the high-risk group. The prognostic ROC curve provides complementary information compared with survival curves. However, when the survival functions do not reach 0, the prognostic ROC curve is incomplete. We show how a range of possible values for the area under the curve can be derived in this situation. A simulation study is performed to analyze the accuracy of this methodology, which is also illustrated by applications to the survival of patients with brain metastases and survival of kidney transplant recipients. PMID- 24240659 TI - Diversity of oat varieties in eliciting the early inflammatory events in celiac disease. AB - PURPOSE: Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic-tryptic digests of the proteins of the oat cultivars. METHODS: K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42-44 in T84 cells were the early gliadin-dependent events studied. RESULTS: The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti gliadin antibodies. CONCLUSION: We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety. PMID- 24240661 TI - Effect of combined application of systemic herbicides on microbial activities in north bengal alluvial soil. AB - An experiment was conducted under laboratory conditions to investigate the effect of combined application of three systemic herbicides, viz., fenoxaprop, pendimethalin and paraquat at 50 g, 1.0 kg and 1.0 kg a.i. ha(-1), respectively, on the changes of microbial biomass C, N and P in relation to transformations and availability of some plant nutrients in an alluvial soil (Typic Orchraqualf) of West Bengal, India. Application of the herbicides, in general, significantly increased microbial biomass C, N and P, resulting in greater availability of C, N and P in soil. The microbial biomass C was highly induced (28.4 %) when fenoxaprop was applied with pendimethalin, while fenoxaprop along with paraquat exerted maximum stimulation towards microbial biomass N (19.9 %) and biomass P (16.2 %). Application of fenoxaprop along with pendimethalin retained the highest amount of organic C (17.4 %), exchangeable NH4(+) (29 %) and available P (19.6 %), while fenoxaprop with paraquat augmented total N and soluble NO3(-) by 21.4 % and 25.2 %, respectively in soil. PMID- 24240662 TI - Metal discharges by Sinaloa Rivers to the coastal zone of NW Mexico. AB - The aim of this work was to survey the discharges of dissolved and particulate Cd, Cu, Fe, Mn, Pb and Zn of the eight main rivers of Sinaloa State to the Mexican coastal environment. Zn was the most abundant dissolved metal and Fe was the most abundant particulate (8.02-16.90 and 51.8-1,140.3 MUg/L, respectively). Only particulate Mn had significantly (p = 0.028) higher values in summer-fall (rainy season), whereas the significantly (p = 0.036) higher values of dissolved Zn were observed in winter and spring. The highest annual total discharges to Sinaloa coastal waters were those of the rivers San Lorenzo and Piaxtla (>2 * 10(3) m.t.) and the lowest those of rivers Baluarte and El Fuerte (349 and 119 m.t., respectively). Pb concentrations may become of concern, because they are higher than the value recommended for the welfare of aquatic communities of natural waters. PMID- 24240660 TI - Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells. AB - Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of alpha-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis. PMID- 24240663 TI - Aging decreases the strength of suprahyoid muscles involved in swallowing movements. AB - Swallowing disorders are common in the elderly, and aging is a factor that affects swallowing function. The elevation of the hyoid bone is important for swallowing and is controlled by the suprahyoid muscles. The hyoid and laryngeal elevation allows the bolus to enter the esophagus. The suprahyoid muscles, therefore, play an important role in swallowing. The effects of aging on suprahyoid muscle strength are unclear. In this study, we analyzed the effects of aging on suprahyoid muscle strength by comparing the jaw opening functions of healthy adults and elderly adults. The subjects were 150 healthy volunteers consisting of 76 adults aged < 70 years (38 men and 38 women; mean age, 48.8 +/- 13.8 years; range, 23-69) and 74 elderly adults aged > 70 years (37 men and 37 women; mean age, 78.1 +/- 4.8 years; range, 70-92). The jaw opening force (JOF) was measured with a jaw opening sthenometer and compared between the healthy adult and elderly groups. The mean JOF of healthy adults was about 10 kg in men and about 6 kg in women, which was significantly greater than the mean JOF of the healthy elderly subjects (about 7 kg in men and about 4 kg in women). The JOF of the men was significantly greater than that of the women in the healthy adult and elderly groups. We thus propose that aging decreases the strength of suprahyoid muscles in healthy adults. The swallowing function may decrease even in healthy adults, aged over 70 years. PMID- 24240664 TI - Decreased serum ghrelin levels in patients with acute myocardial infarction. AB - Ghrelin is a novel growth hormone-releasing peptide isolated from the stomach and possesses various cardioprotective effects, including energy balance improvement and regulation of autonomic nervous system activity. We investigated the changes in serum ghrelin levels and its association with cardiac function and myocardial infarct size in patients with acute myocardial infarction (AMI). Forty-seven consecutive patients were divided into the following 4 groups: 16 patients with AMI, 12 patients with unstable angina pectoris (UAP), 13 patients with stable angina pectoris (SAP), and 6 control patients. Serum levels were measured with the ELISA kit. Compared to the control (72 +/- 26 fmol/mL), SAP (69 +/- 47 fmol/mL), and UAP (72 +/- 31 fmol/mL) groups, serum ghrelin levels on admission were significantly lower in the AMI group (27 +/- 12 fmol/mL, P < 0.01). After admission, the serum ghrelin level gradually increased (30 +/- 15 fmol/mL on day 2 and 39 +/- 18 fmol/mL on day 7) and became significantly higher on day 14 (49 +/- 28 fmol/mL, P < 0.01), compared to the level on admission. In patients with AMI, the ratio of day 14 to admission serum ghrelin levels, an index of AMI related acute changes in ghrelin, correlated positively with peak creatine phosphokinase levels (R = 0.72, P < 0.01) and the double products (R = 0.60, P < 0.01) and inversely with left ventricular ejection fraction (R = -0.53, P < 0.05). In conclusion, serum ghrelin levels are significantly decreased in association with myocardial infarct size and cardiac function. PMID- 24240665 TI - Addressing the taboo of medical error through IGBOs: I got burnt once! AB - BACKGROUND: An I Got Burnt Once (IGBO) is a near-miss or actual clinical event, related to patient safety, that leaves a lasting impact on the health professional (HP) involved. The purpose of this study was to collect and categorize IGBOs from a variety of pediatric HPs and to determine whether the individual's clinical practice was altered as a result. METHODS: Semistructured interviews involved recollection of an IGBO and subsequent changes in clinical practice. The IGBOs were classified into one of the seven Canadian Medical Education Directives for Specialists (CanMEDS) roles and outcome of the event. RESULTS: Of the 38 pediatric HPs approached (25 doctors and 13 female nurses), 35 recalled an IGBO. Most (74 %) were classified to the CanMEDS Medical Expert role (with subcategorization into diagnostics (37 %), treatment (34 %), and clinical management (31 %) followed by communicator (14 %) and collaborator (12 %) roles). Half (55 %) of the respondents considered the IGBO event to be potentially life threatening event to the patient, resulting in no harm (63 %), disability (14 %), and fatality in 17 % of the cases. Most respondents (92 %) stated that IGBOs affected their medical practice for months and sometimes years after the event. CONCLUSIONS: Most practitioners can recall an IGBO in their clinical practice. IGBOs may be a potential source of medical risk avoidance and reduction strategies, and worthy of further investigation by "deep dives" or root cause analysis. PMID- 24240666 TI - A prospective randomly controlled clinical trial on azithromycin therapy for induction treatment of children with nephrotic syndrome. AB - A prospective study was designed to evaluate the efficacy of azithromycin (AZM) when combined with prednisone therapy compared with prednisone therapy alone in children with primary nephrotic syndrome (PNS) undergoing induction treatment. A prospective randomly controlled clinical trial was conducted. Randomization was performed to select the research subjects who were composed of children with PNS and treated with AZM combined with prednisone (the intervention group) and with prednisone alone (the control group). A total of 211 randomly selected patients with PNS received either AZM combined with prednisone (n = 106) or prednisone alone (n = 105) for 6 months. At three months in the follow-up period, 12 patients were lost to follow up (intervention group, 7; control group, 5), and 6 patients had a transient hypocomplementemia (intervention group, 4 ; control group, 2). AZM was administered at a dose of 10 mg/kg q.d (1 dose per day) for three consecutive days. The median duration before remission was 6 days in the intervention group and 9 days in the control group (p < 0.0001). Relapse rate differed among the groups at 3 months (11.6 vs. 21.4 %, p = 0.049). No difference in relapse rate was observed between the two groups within 4 to 6 months and at 6 months (p = 0.168, 0.052). After 4 weeks of treatment, steroid resistance occurred in 1 out of 95 (1.05 %) patients in the intervention group and in 10 out of 98 (10.2 %) patients in the control group (p = 0.006). After 8 weeks of treatment, no difference was found in steroid resistance between two groups (1/95 vs. 3/98, p = 0.327). During follow-up at 6 months, no difference was exhibited by the two groups on frequent relapse rates (p = 0.134). CONCLUSION: If a course of AZM is added to the glucocorticoid-induced treatment among children with PNS, then the sensitivity of prednisone increases. This increase consequently reduces duration to remission and decreases relapse. However, further studies are necessary to confirm these results. PMID- 24240667 TI - Dietary total antioxidant capacity and current asthma in Spanish schoolchildren: a case control-control study. AB - The aim of this work was to study the relationship between dietary total antioxidant capacity (TAC) and current asthma in a group of Spanish schoolchildren. A total of 78 Spanish schoolchildren (26 asthmatic and 52 healthy controls) were randomly selected from a cohort of 564 children (9-12 years of age). The weight and height of all subjects were recorded. A questionnaire, completed by the subjects' parents, was used to obtain personal and health information. Current asthma was established when children had ever had asthma, they had been diagnosed with asthma by a physician, and they had been treated with medications at some time in the previous 12 months. Food intake was monitored using a 3-day food record. All consumed foods were converted into energy and nutrients. Dietary TAC was evaluated using the ferric reducing antioxidant power (FRAP), radical-trapping antioxidant parameter (TRAP), and Trolox equivalent antioxidant capacity (TEAC) assays. The TAC measured using all the assays was significantly lower in children with asthma than in children without this condition (2.95 (2.10-3.75) mmol Fe(II)/day vs. 3.70 (3.08-4.49) mmol Fe(II)/day, p < 0.01; 1.50 (1.06-2.05) mmol Trolox equivalents/day vs. 2.10 (1.40-2.65) mmol Trolox equivalents/day, p < 0.05; and 1.60 (1.08-2.00) mmol Trolox equivalents/day vs. 1.85 (1.50-2.68) mmol Trolox equivalents/day, p < 0.05 for FRAP, TEAC, and TRAP, respectively). After adjusting for energy intake, children with FRAP values higher than 3.5 mmol Fe(II)/day (p50) and TEAC values higher than 1.9 mmol Trolox equivalents/day (p50) had 22.6 and 35.0 %, respectively, lower likelihood of suffering asthma episodes than children with lower values. When logistic regression analysis was performed separately for children with nonsmoker and smoker (at least one) parents, the association between dietary TAC and asthma was only observed in the nonsmoker group (OR = 0.257, 95 % CI = 0.107-0.618, p = 0.002 for FRAP; OR = 0.212, 95 % CI = 0.069 0.639, p = 0.006 for TEAC; and OR = 0.264, 95 % CI = 0.091-0.769, p = 0.015 for TRAP assay). CONCLUSION: Dietary TAC may have a favorable role in asthma in children and, specially, in those with nonsmoker parents. PMID- 24240668 TI - Randomized clinical trial progress to inform care for out-of-hospital cardiac arrest. PMID- 24240670 TI - Impact of intraoperative distractions on patient safety: a prospective descriptive study using validated instruments. AB - BACKGROUND: There is emerging evidence indicating that distractions in the operating room (OR) are prevalent. Studies have shown a negative impact of distractions, but they have been conducted mostly with residents in simulated environments. We tested the hypothesis that intraoperative distractions are associated with deterioration in patient safety checks in the OR. METHODS: We assessed 24 elective urologic procedures. Blinded trained assessors (two surgeons, one psychologist) used validated instruments to prospectively assess in vivo frequency and severity of distractions (related to communication, phones/pagers, equipment/provisions, OR environment, other hospital departments, or a member of the OR team) and completion of safety-related tasks (related to the patient, equipment, and communication). Descriptive and correlational analyses were conducted. RESULTS: Mean case duration was 70 min (mean intraoperative time 31 min). A mean of 4.0 communication distractions (range 0-9) and 2.48 other distractions (range 0-5) were recorded per case (distraction rate of one per 10 min). Distractions from external visitors (addressed to the entire team or the surgeon) and distractions due to lack of coordination between hospital departments were most disruptive. Regarding safety checks, patient tasks were completed most often (85-100 %) followed by equipment tasks (75-100 %) and communication tasks (55-90 %). Correlational analyses showed that more frequent/severe communication distractions were linked to lower completion of patient checks intraoperatively (median rho -0.56, p < 0.05). CONCLUSIONS: Distractions are prevalent in ORs and in this study were linked to deterioration in intraoperative patient safety checks. Surgeons should be mindful of their tolerance to distractions. Surgical leadership can help control distractions and reduce their potential impact on patient safety and performance. PMID- 24240671 TI - Synchronous bilateral adrenalectomy for Cushing's syndrome: laparoscopic versus posterior retroperitoneoscopic versus robotic approach. AB - BACKGROUND: Synchronous endoscopic bilateral adrenalectomy (BilA) can effectively provide definitive cure of hypercortisolism in ACTH-dependent Cushing's syndrome and in primary adrenal bilateral disease. We compared three different approaches for BilA: transabdominal laparoscopic BilA (TL-BilA), simultaneous posterior retroperitoneoscopic BilA (PR-BilA), and robot-assisted BilA (RA-BilA). METHODS: All patients who underwent BilA between January 1999 and December 2012 at two referral centers (one performing TL-BilA and PR-BilA and one performing RA-BilA) were included. A comparative analysis was performed. RESULTS: Twenty-nine patients were included: 5 underwent TL-BilA, 11 underwent PR-BilA, and 13 underwent RA-BilA. No significant difference was found concerning age, gender, diagnosis, and previous abdominal surgery. No conversion to open approach was registered. Operative time was significantly shorter for the PR-BilA group than for the TL-BilA and RA-BilA groups (157.4 +/- 54.6 vs 256.0 +/- 43.4 vs 221.5 +/- 42.2 min, respectively) (P < 0.001). No significant difference was found concerning intraoperative and postoperative complications rate and time to first flatus. Drains were used routinely after PR-BilA and TL-BilA and electively in four RA-BilA patients (P < 0.001). Hospital stay was longer in the TL-BilA and PR BilA groups than in the RA-BilA group (12.0 +/- 5.7 vs 10.8 +/- 3.7 vs 4.4 +/- 1.7 days, respectively) (P < 0.001). No recurrence or disease-related death was registered. CONCLUSIONS: Operative time was significantly shorter in the PR-BilA group, because it eliminates the need to reposition the patient. The number of drains and the length of hospital stay were reduced after RA-BilA, but this was likely related to different management protocols in different settings. Because no significant difference was found in terms of postoperative outcome, none of the three operative approaches can be considered the preferable one. PMID- 24240672 TI - Cure predictability during parathyroidectomy. AB - BACKGROUND: A mathematical model for primary hyperparathyroidism (1 degrees HPTH) was developed and embedded in software to yield intraoperative predictability curves. METHODS: A total of 1,754 consecutive 1 degrees HPTH operative cases were screened to select 617 [554 single adenoma (SA), 63 multigland] patients with complete preoperative, intraoperative (pre-exploration, time 0, every 5 min post resection), and postoperative parathyroid hormone (PTH) and calcium data. Data transformations and models were hypothesized and tested, including inverse functions, differences, half-lives, differences from projected half-lives, second order kinetics, second-order derivatives, and time-dependent ratios. Sub-models of ratios were developed for time-dependent and initial-value combinations. For each time segment the log odds were modeled using multiple logistic stepwise regression. An idealized model was selected, embedded in software, and installed in a laptop computer to enable intraoperative decision analyses, PTH curve plotting, and storage and transmission of data. A subsequent cohort of 100 consecutive unselected patients [81 SAs, 19 multigland (13 hyperplasia, 2 MEN1, 1 lithium, 3 double adenomas)] inclusive of seven remedial cervical explorations were tested. RESULTS: The model predicted an overall curative resection in 95 % of patients. In SA patients, cure was predicted in 78/81 patients with a mean probability of 99.3 % at 11.8 +/- 10.4 min post-resection. In three cured patients, the software failed to suggest cure, because of a low baseline PTH or delayed clearance. The model also correctly predicted residual hyperfunctioning tissue in all tested multigland patients. All multigland patients underwent additional exploration with resection of residual disease resulting in a mean predicted cure rate of 97.9 % at 10.6 +/- 7.3 min post-resection completion in 17 patients. In two patients, the software predicted a mean cure rate of 22 % due to either a low PTH baseline or delayed clearance. Overall, the software accurately predicted cure in 95 of 100 cured cases. CONCLUSIONS: This intraoperative prediction software expedites termination of surgery with a high level of curative confidence. Alternatively, the model accurately predicts residual disease prompting additional exploration. Because the model is based on a large set of multivariate regression curves, PTH values obtained at any post-resection sampling interval generate prediction data with far greater accuracy than existing algorithms. The software is designed for convenient operative use and can print, store, and electronically transmit probability analyses and PTH curves in real-time. PMID- 24240673 TI - Postoperative portomesenteric venous thrombosis: lessons learned from 1,069 consecutive laparoscopic colorectal resections. AB - BACKGROUND: Portomesenteric venous thrombosis (PVT) is a known complication after open and laparoscopic colorectal (LCR) surgery. Risk factors and the prognosis of PVT have been poorly described. METHODS: This study is a retrospective analysis of a prospectively collected database. Patients with new-onset postoperative abdominal pain were evaluated with a computed tomography scan of the abdomen. Patients found to have PVT were analyzed. A multivariate analysis was performed to identify predictors of PVT. RESULTS: A total of 1,069 patients undergoing LCR surgery for inflammatory bowel disease (IBD) or nonmetastatic cancer between June 2002 and June 2012 were included. Altogether, 37 (3.5 %) patients experienced symptomatic postoperative PVT. On univariate analysis, IBD (p < 0.001), ulcerative colitis (p = 0.016), preoperative therapy with steroids (p = 0.008), operative time >=220 min (p = 0.004), total proctocolectomy (TPC) (p < 0.001), ileoanal pouch anastomosis (p = 0.006), and postoperative intraabdominal septic complications (p < 0.001) were found to be significant risk factors. By multivariate analysis, TPC (p = 0.026) and postoperative intraabdominal septic complications (p < 0.001) were independent predictors of PVT. In the PVT group, postoperative length of stay was longer (14.8 vs. 7.4 days, p < 0.001). Of the patients evaluated with a hematologic workup, 72.7 % were found to have a hypercoagulable condition. All patients were managed with oral anticoagulation for at least 6 months. No death or complications related to PVT occurred. CONCLUSIONS: PVT is a potentially serious complication that is more likely to occur after TPC and in the presence of postoperative intraabdominal septic complications, particularly in patients with a coagulation disorder. Prompt diagnosis and treatment with oral anticoagulation are recommended to avoid long term sequelae. PMID- 24240674 TI - Thyroid nodules with benign cytology: is size >= 4 cm an indication for surgery? PMID- 24240675 TI - Laparoscopy-assisted hybrid left-side donor hepatectomy: rationale for performing LADH. PMID- 24240676 TI - Preparing for prospective clinical trials: a national initiative of an excellence registry for consecutive pancreatic cancer resections. PMID- 24240677 TI - Letter to the editor. PMID- 24240680 TI - Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition. AB - RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12 dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in allele to elucidate the early events after Hras activation, and to evaluate the therapeutic effectiveness of farnesyltransferase inhibition (FTI). Treatment of Caggs-Cre/FR-Hras(G12V) mice with TPA alone was sufficient to trigger papilloma development with a shorter latency and an ~10-fold greater tumor burden than DMBA/TPA-treated WT-controls. Hras(G12V) allele copy number was increased in all papillomas induced by TPA. DMBA/TPA treatment of Hras(G12V) knock-in mice induced an even greater incidence of papillomas, which either harbored Hras(G12V) amplification or developed an Hras(Q61L) mutation in the second allele. Laser capture microdissection of normal skin, hyperplastic skin and papillomas showed that amplification occurred only at the papilloma stage. HRAS-mutant allelic imbalance was also observed in human cancer cell lines, consistent with a requirement for augmented oncogenic HRAS signaling for tumor development. The FTI SCH66336 blocks HRAS farnesylation and delocalizes it from the plasma membrane. NRAS and KRAS are not affected as they are alternatively prenylated. When tested in lines harboring HRAS, NRAS or KRAS mutations, SCH66336 delocalized, inhibited signaling and preferentially inhibited growth only of HRAS-mutant lines. Treatment with SCH66336 also induced near-complete regression of papillomas of TPA-treated Hras(G12V) knock-in mice. These data suggest that farnesyl transferase inhibitors should be reevaluated as targeted agents for human HRAS driven cancers, such as those of bladder, thyroid and other epithelial lineages. PMID- 24240679 TI - Toward a therapeutic reduction of imatinib refractory myeloproliferative neoplasm initiating cells. AB - Myeloproliferative neoplasms (MPNs) such as chronic myelogenous (CML) and chronic myelomonocytic leukemias (CMML) are frequently induced by tyrosine kinase oncogenes. Although these MPNs are sensitive to tyrosine kinase inhibitors such as imatinib, patients often relapse upon withdrawal of therapy. We used a model of MPN, which is induced by co-expression of the oncoproteins HIP1/PDGFbetaR (H/P) and AML1/ETO from their endogenous loci, to examine the mechanisms of disease development and recurrence following imatinib withdrawal. Although the MPN displayed a full hematologic response to imatinib, 100% of the diseased mice relapsed upon drug withdrawal. MPN persistence was not due to imatinib resistance mutations in the H/P oncogene or massive gene expression changes. Within 1 week of imatinib treatment, more than 98% of gene expression changes induced by the oncogenes in isolated hematopoietic stem and progenitor cells (lineage(-)Sca 1(+)c-Kit(+) immunophenotype) normalized. Supplementation of imatinib with granulocyte colony-stimulating factor or arsenic trioxide reduced MPN-initiating cell frequencies and the combination of imatinib with arsenic trioxide cured a large fraction of mice with MPNs. In contrast, no mice in the imatinib-treated control cohorts were cured. These data suggest that treatment with a combination of arsenic trioxide and imatinib can eliminate refractory MPN-initiating cells and reduce disease relapse. PMID- 24240681 TI - Arylsulfatase B regulates versican expression by galectin-3 and AP-1 mediated transcriptional effects. AB - Arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB) removes 4-sulfate groups from chondroitin-4-sulfate (C4S) and dermatan sulfate and is required for their degradation. In human prostate stromal and epithelial cells, when ARSB was silenced, C4S, versican and versican promoter activity increased, and the galectin-3 that co-immunoprecipitated with C4S declined. Galectin-3 silencing inhibited the ARSB-silencing-induced increases in versican and versican promoter due to effects on the AP-1-binding site in the versican promoter. These findings demonstrate for the first time the transcriptional mechanism whereby ARSB can regulate expression of an extracellular matrix proteoglycan with C4S attachments. In addition, following ARSB silencing, C4S that co-immunoprecipitated with versican increased, whereas co-immunoprecipitated EGFR declined, total EGFR increased and exogenous EGF-induced cell proliferation increased, suggesting profound effects of ARSB on vital cell processes. PMID- 24240682 TI - MicroRNAs and cancer stem cells: the sword and the shield. AB - Emerging chemotherapy drugs and targeted therapies have been widely applied in anticancer treatment and have given oncologists a promising future. Nevertheless, regeneration and recurrence are still huge obstacles on the way to cure cancer. Cancer stem cells (CSCs) are capable of self-renewal, tumor initiation, recurrence, metastasis, therapy resistance, and reside as a subset in many, if not all, cancers. Therefore, therapeutics specifically targeting and killing CSCs are being identified, and may be promising and effective strategies to eliminate cancer. MicroRNAs (miRNAs, miRs), small noncoding RNAs regulating gene expression in a post-transcriptional manner, are dysregulated in most malignancies and are identified as important regulators of CSCs. However, limited knowledge exists for biological and molecular mechanism by which miRNAs regulate CSCs. In this article, we review CSCs, miRNAs and the interactions between miRNA regulation and CSCs, with a specific focus on the molecular mechanisms and clinical applications. This review will help us to know in detail how CSCs are regulated by miRNAs networks and also help to develop more effective and secure miRNA-based clinical therapies. PMID- 24240683 TI - PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. AB - PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. Further, in blast crisis chronic myeloid leukaemia, and a subset of acute myeloid leukaemias, PRH is aberrantly localised and its activity is downregulated. Here we show that PRH is involved in the regulation of cell migration and cancer cell invasion. We show for the first time that PRH is expressed in prostate cells and that a decrease in PRH protein levels increases the migration of normal prostate epithelial cells. We show that a decrease in PRH protein levels also increases the migration of normal breast epithelial cells. Conversely, PRH overexpression inhibits cell migration and cell invasion by PC3 and DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. Previous work has shown that the transforming growth factor-beta co-receptor Endoglin inhibits the migration of prostate and breast cancer cells. Here we show that PRH can bind to the Endoglin promoter in immortalised prostate and breast cells. PRH overexpression in these cells results in increased Endoglin protein expression, whereas PRH knockdown results in decreased Endoglin protein expression. Moreover, we demonstrate that Endoglin overexpression abrogates the increased migration shown by PRH knockdown cells. Our data suggest that PRH controls the migration of multiple epithelial cell lineages in part at least through the direct transcriptional regulation of Endoglin. We discuss these results in terms of the functions of PRH in normal cells and the mislocalisation of PRH seen in multiple cancer cell types. PMID- 24240685 TI - FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. AB - Ubiquitin linkage is critical in directing the cellular fate of a ubiquitinated protein. Although K48-linked polyubiquitination of p53 leads to its degradation, whether K48-independent ubiquitin linkages are involved in p53 activation remains unknown. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53. Knockdown of FATS impairs p53 stabilization and activation in response to DNA damage. Furthermore, the NH2-terminal domain of FATS is sufficient to exhibit ubiquitin ligase (E3) activity and assemble ubiquitin polymers through K11-, K29- and K63-linkages, independently of the ubiquitin-conjugating enzyme (E2). FATS promotes p53-dependent transcription of p21, leading to robust checkpoint response. The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage. Our findings reveal K48-linkage-independent non-linear polyubiquitination of p53 as a new barcode for p53 activation. PMID- 24240686 TI - The tumor suppressor, TAX1BP2, is a novel substrate of ATM kinase. AB - DNA damage repair response is a crucial process for cancer prevention. One of the key regulators of this process is ataxia telangiectasia mutated (ATM) kinase, which modulates the p53 level by direct and indirect phosphorylation. Recent data showed that ATM also localizes at the centrosome, but the function remains elusive. TAX1BP2 was initially identified as a novel centrosomal protein that interacts directly with the human T-cell leukemia virus type 1 (HTLV-1)-encoded oncoprotein, Tax, and inhibits centrosome overduplication. Subsequently, TAX1BP2 was found to be a tumor suppressor in hepatocellular carcinoma, and accumulation of TAX1BP2 was observed upon chemotherapeutic drug treatment. Here, we provide evidence that TAX1BP2 is a direct phosphorylation substrate of ATM. The protein level of TAX1BP2 is significantly upregulated in response to DNA damaging agents. Serine-922 of TAX1BP2 is the phosphorylation site of ATM, and such phosphorylation modulates the protein stability, ubiquitination and tumor suppressor activity of TAX1BP2. Taken together, we demonstrate for the first time that TAX1BP2 is a novel effector of ATM in DNA damage response and delineated a new mechanism by which ATM stabilizes the tumor suppressor TAX1BP2. PMID- 24240684 TI - Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma. AB - We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed. PMID- 24240687 TI - N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 is overexpressed in cancer and promotes a pro-migratory and pro-metastatic phenotype. AB - N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 (NAALADL2) is a member of the glutamate carboxypeptidase II family, best characterized by prostate-specific membrane antigen (PSMA/NAALAD1). Using immunohistochemistry (IHC), we have shown overexpression of NAALADL2 in colon and prostate tumours when compared with benign tissue. In prostate cancer, NAALADL2 expression was associated with stage and Grade, as well as circulating mRNA levels of the NAALADL2 gene. Overexpression of NAALADL2 was shown to predict poor survival following radical prostatectomy. In contrast to PSMA/NAALAD1, NAALADL2 was localized at the basal cell surface where it promotes adhesion to extracellular matrix proteins. Using stable knockdown and overexpression cell lines, we have demonstrated NAALADL2 dependent changes in cell migration, invasion and colony-forming potential. Expression arrays of the knockdown and overexpression cell lines have identified nine genes that co-expressed with NAALADL2, which included membrane proteins and genes known to be androgen regulated, including the prostate cancer biomarkers AGR2 and SPON2. Androgen regulation was confirmed in a number of these genes, although NAALADL2 itself was not found to be androgen regulated. NAALADL2 was also found to regulate levels of Ser133 phosphorylated C-AMP-binding protein (CREB), a master regulator of a number of cellular processes involved in cancer development and progression. In combination, these data suggest that changes in expression of NAALADL2 can impact upon a number of pro-oncogenic pathways and processes, making it a useful biomarker for both diagnosis and prognosis. PMID- 24240688 TI - Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis. AB - Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability. PMID- 24240689 TI - Preclinical validation of AXL receptor as a target for antibody-based pancreatic cancer immunotherapy. AB - AXL receptor tyrosine kinase (RTK) is implicated in proliferation and invasion of many cancers, particularly in pancreatic ductal adenocarcinoma (PDAC), for which new therapeutic options are urgently required. We investigated whether inhibition of AXL activity by specific monoclonal antibodies (mAbs) is efficient in limiting proliferation and migration of pancreatic cancer cells. Expression of AXL was evaluated by immunohistochemistry in 42 PDAC. The AXL role in oncogenesis was studied using the short hairpin RNA approach in a pancreatic carcinoma cell line. We further generated antihuman AXL mAbs and evaluated their inhibitory effects and the AXL downstream signaling pathways first in vitro, in a panel of pancreatic cancer cell lines and then in vivo, using subcutaneous or orthotopic pancreatic tumor xenografts. AXL receptor was found expressed in 76% (32/42) of PDAC and was predominantly present in invasive cells. The AXL-knockdown Panc-1 cells decreased in vitro cell migration, survival and proliferation, and reduced in vivo tumor growth. Two selected anti-AXL mAbs (D9 and E8), which inhibited phosphorylation of AXL and of its downstream target AKT without affecting growth arrest-specific factor 6 (GAS6) binding, induced downexpression of AXL by internalization, leading to an inhibition of proliferation and migration in the four pancreatic cancer cell lines studied. In vivo, treatment by anti-AXL mAbs significantly reduced growth of both subcutaneous and orthotopic pancreatic tumor xenografts independently of their KRAS mutation status. Our in vitro and preclinical in vivo data demonstrate that anti-human AXL mAbs could represent a new approach to the pancreatic cancer immunotherapy. PMID- 24240691 TI - Thrombolytic therapy in the treatment of acute sub-massive pulmonary embolism: a prospective observational study. AB - The use of thrombolytic therapy in haemodynamically stable patients with sub massive pulmonary embolism is still controversial. We conducted this study to observe the safety and efficacy of thrombolytic therapy in acute pulmonary embolism patients with normal blood pressure in a tertiary cardiac centre. In this study, 130 patients with sub-massive pulmonary embolism who had right ventricular dysfunction were included and treated with thrombolytic therapy. Forty-one percent of patients in our study were within 40 years of age. Eighty three percent of patients had clinical improvement. Both right-ventricular dysfunction and pulmonary artery systolic pressure were improved significantly following thrombolytic therapy from baseline (49 vs. 28 mmHg; P = 0.01; 95% confidence interval -13 to -56). Only 9% patients had died and two patients had intra-cerebral haemorrhage during this study. Thrombolytic therapy may be helpful in improving clinical course following sub-massive acute pulmonary embolism, especially for those who had low risk of bleeding. Further randomized study with large sample size is needed for final conclusion. PMID- 24240690 TI - Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells. AB - We show that expression of the microtubule depolymerizing kinesin KIF2C is induced by transformation of immortalized human bronchial epithelial cells (HBEC) by expression of K-Ras(G12V) and knockdown of p53. Further investigation demonstrates that this is due to the K-Ras/ERK1/2 MAPK pathway, as loss of p53 had little effect on KIF2C expression. In addition to KIF2C, we also found that the related kinesin KIF2A is modestly upregulated in this model system; both proteins are expressed more highly in many lung cancer cell lines compared to normal tissue. As a consequence of their depolymerizing activity, these kinesins increase dynamic instability of microtubules. Depletion of either of these kinesins impairs the ability of cells transformed with mutant K-Ras to migrate and invade matrigel. However, depletion of these kinesins does not reverse the epithelial to mesenchymal transition (EMT) caused by mutant K-Ras. Our studies indicate that increased expression of microtubule destabilizing factors can occur during oncogenesis to support enhanced migration and invasion of tumor cells. PMID- 24240692 TI - An EPR/HYSCORE, Mossbauer, and resonance Raman study of the hydrogenase maturation enzyme HydF: a model for N-coordination to [4Fe-4S] clusters. AB - The biosynthesis of the organometallic H cluster of [Fe-Fe] hydrogenase requires three accessory proteins, two of which (HydE and HydG) belong to the radical S adenosylmethionine enzyme superfamily. The third, HydF, is an Fe-S protein with GTPase activity. The [4Fe-4S] cluster of HydF is bound to the polypeptide chain through only the three, conserved, cysteine residues present in the binding sequence motif CysXHisX(46-53)HisCysXXCys. However, the involvement of the two highly conserved histidines as a fourth ligand for the cluster coordination is controversial. In this study, we set out to characterize further the [4Fe-4S] cluster of HydF using Mossbauer, EPR, hyperfine sublevel correlation (HYSCORE), and resonance Raman spectroscopy in order to investigate the influence of nitrogen ligands on the spectroscopic properties of [4Fe-4S](2+/+) clusters. Our results show that Mossbauer, resonance Raman, and EPR spectroscopy are not able to readily discriminate between the imidazole-coordinated [4Fe-4S] cluster and the non-imidazole-bound [4Fe-4S] cluster with an exchangeable fourth ligand that is present in wild-type HydF. HYSCORE spectroscopy, on the other hand, detects the presence of an imidazole/histidine ligand on the cluster on the basis of the appearance of a specific spectral pattern in the strongly coupled region, with a coupling constant of approximately 6 MHz. We also discovered that a His-tagged version of HydF, with a hexahistidine tag at the N-terminus, has a [4Fe-4S] cluster coordinated by one histidine from the tag. This observation strongly indicates that care has to be taken in the analysis of data obtained on tagged forms of metalloproteins. PMID- 24240693 TI - Evolving wonder-RNAs in a test tube. PMID- 24240694 TI - Linking up: the graying of AIDS. PMID- 24240695 TI - Primitive myxoid mesenchymal tumor of infancy with rosettes: a new finding and literature review. AB - Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a relatively recently described tumor arising in infants and demonstrating a unique histomorphology. We present an unusual case of PMMTI with rosettes, a hitherto undescribed finding in the reported cases. We also present the cytogenetic and ultrastructural findings of this tumor and review the literature. As awareness of PMMTI increases, additional clinical data and histopathologic findings will aid in the morphologic and behavioral characterization of this neoplasm. PMID- 24240696 TI - A New Type of Renal Cancer--Tubulocystic Carcinoma of the Kidney: A Review of the Literature. AB - In 2004, A new peculiar subtype of renal cell carcinoma, which later received the name of tubulocystic carcinoma (TCC-RC), was recognized. Though the tumor has distinct macroscopic, microscopic and immunohistochemical features, the tumor was previously considered to have some similarities to various other renal cancers. We did an extensive review of literature using PubMed and CrossRef, which yielded more than 80 cases reported from various parts of the world. We evaluated the epidemiology, tumor presentations, pathological characteristics, treatment, and outcome of TCC-RC. PMID- 24240697 TI - Oral fibroma with HPV-associated epithelial dysplasia: even in fibromas you should look for the unexpected. AB - Fibromas are the most common soft tissue lesions of the oral cavity and are generally attributed to trauma. Koilocytic dysplasia refers to human papillomavirus (HPV)-related epithelial cytopathic effect. Koilocytic dysplasia is considered neoplastic. Herein, we report a case of oral fibroma with HPV induced dysplastic changes of the surface epithelium confirmed by immunohistochemical stains for p16 and p53 as well as HPV in situ hybridization. PMID- 24240698 TI - Epithelia of the ovine and bovine forestomach express basolateral maxi-anion channels permeable to the anions of short-chain fatty acids. AB - It has long been established that the absorption of short-chain fatty acids (SCFA) across epithelia stimulates sodium proton exchange. The apically released protons are not available as countercations for the basolateral efflux of SCFA anions and a suitable transport model is lacking. Patch clamp and microelectrode techniques were used to characterize an anion conductance expressed by cultured cells of the sheep and bovine rumen and the sheep omasum and to localize the conductance in the intact tissue. Cells were filled with a Na-gluconate solution and superfused with sodium salts of acetate, propionate, butyrate, or lactate. Reversal potential rose and whole cell current at +100 mV decreased with the size of the anion. Anion-induced currents could be blocked by diisothiocyanato stilbene-2,2'-disulfonic acid (DIDS), NPPB (200 MUmol l(-1)), or pCMB (1 mmol l( 1)). In patches of bovine ruminal cells, single channels were observed with a conductance for chloride (327 +/- 11 pS), acetate (115 +/- 8 pS), propionate (102 +/- 10 pS), butyrate (81 +/- 2 pS), and gluconate (44 +/- 3 pS). Channels expressed by sheep rumen and omasum were similar. Microelectrode experiments suggest basolateral localization. In conclusion, forestomach epithelia express basolateral maxi-anion channels with a permeability sequence of chloride > acetate > propionate > butyrate. SCFA absorption may resemble functionally coupled transport of NaCl, with the Na(+)/K(+)-ATPase driving the basolateral efflux of the anion through a channel. Since protons are apically extruded, the model accurately predicts that influx of buffers with saliva is essential for the pH homeostasis of the ruminant forestomach. PMID- 24240701 TI - SIRT1 and AMPK mediate hypoxia-induced resistance of non-small cell lung cancers to cisplatin and doxorubicin. AB - SIRT1 is an NAD(+)-dependent protein deacetylase induced by metabolic stresses, such as nutrition or oxygen deprivation. Although SIRT1 contributes to aging and metabolic disorders, its role in cancer progression and therapeutic responses remains controversial. Because hypoxia occurs widely in solid tumors, where it provokes drug resistance, we investigated the involvement of SIRT1 in hypoxia induced chemoresistance. SIRT1 was downregulated in a panel of non-small cell lung carcinoma (NSCLC) cells exposed to hypoxia for 48 hours. The master metabolic kinase AMP-activated protein kinase (AMPK) was inactivated under the same conditions, likely due to attenuation of the SIRT1/LKB1-mediated AMPK activation process. Notably, hypoxic inactivation of this SIRT1-AMPK pathway led to cisplatin and doxorubicin resistance. Mechanistic investigations suggested that this pathway supported the cytotoxic response to cisplatin and doxorubicin by licensing an apoptotic process controlled by mitochondria. We confirmed the involvement of this pathway in a mouse xenograft model of human NSCLC. Furthermore, we demonstrated that a SIRT1 activator SRT1720 augmented the antitumor effects of cisplatin, and these effects could be blocked by administration of an AMPK inhibitor compound C. Taken together, our results offer preclinical proof-of-concept to target the SIRT1-AMPK pathway as a strategy to overcome hypoxia-induced chemoresistance in NSCLC. PMID- 24240699 TI - Mechanism and synergism in epithelial fluid and electrolyte secretion. AB - A central function of epithelia is the control of the volume and electrolyte composition of bodily fluids through vectorial transport of electrolytes and the obligatory H2O. In exocrine glands, fluid and electrolyte secretion is carried out by both acinar and duct cells, with the portion of fluid secreted by each cell type varying among glands. All acinar cells secrete isotonic, plasma-like fluid, while the duct determines the final electrolyte composition of the fluid by absorbing most of the Cl(-) and secreting HCO3 (-). The key transporters mediating acinar fluid and electrolyte secretion are the basolateral Na(+)/K(+) /2Cl(-) cotransporter, the luminal Ca(2+)-activated Cl(-) channel ANO1 and basolateral and luminal Ca(2+)-activated K(+) channels. Ductal fluid and HCO3 (-) secretion are mediated by the basolateral membrane Na(+)-HCO3 (-) cotransporter NBCe1-B and the luminal membrane Cl(-)/HCO3 (-) exchanger slc26a6 and the Cl(-) channel CFTR. The function of the transporters is regulated by multiple inputs, which in the duct include major regulation by the WNK/SPAK pathway that inhibit secretion and the IRBIT/PP1 pathway that antagonize the effects of the WNK/SPAK pathway to both stimulate and coordinate the secretion. The function of these regulatory pathways in secretory glands acinar cells is yet to be examined. An important concept in biology is synergism among signaling pathways to generate the final physiological response that ensures regulation with high fidelity and guards against cell toxicity. While synergism is observed in all epithelial functions, the molecular mechanism mediating the synergism is not known. Recent work reveals a central role for IRBIT as a third messenger that integrates and synergizes the function of the Ca(2+) and cAMP signaling pathways in activation of epithelial fluid and electrolyte secretion. These concepts are discussed in this review using secretion by the pancreatic and salivary gland ducts as model systems. PMID- 24240700 TI - Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. AB - Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that additional genetic determinants might direct use of these drugs, we conducted a genome-wide synthetic lethal screen for candidate olaparib sensitivity genes. In support of this hypothesis, the set of identified genes included known determinants of olaparib sensitivity, such as BRCA1, RAD51, and Fanconi's anemia susceptibility genes. In addition, the set included genes implicated in established networks of DNA repair, DNA cohesion, and chromatin remodeling, none of which were known previously to confer sensitivity to PARP1/2 inhibition. Notably, integration of the list of candidate sensitivity genes with data from tumor DNA sequencing studies identified CDK12 deficiency as a clinically relevant biomarker of PARP1/2 inhibitor sensitivity. In models of high grade serous ovarian cancer (HGS-OVCa), CDK12 attenuation was sufficient to confer sensitivity to PARP1/2 inhibition, suppression of DNA repair via homologous recombination, and reduced expression of BRCA1. As one of only nine genes known to be significantly mutated in HGS-OVCa, CDK12 has properties that should confirm interest in its use as a biomarker, particularly in ongoing clinical trials of PARP1/2 inhibitors and other agents that trigger replication fork arrest. PMID- 24240702 TI - A novel EGFR isoform confers increased invasiveness to cancer cells. AB - As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform termed EGFRvA, which substitutes a Ser/Thr-rich peptide for part of the carboxyl-terminal regulatory domain of the receptor. Intriguingly, EGFRvA expression relates more closely to histopathologic grade and poor prognosis in patients with glioma. Ectopic expression of EGFRvA in cancer cells conferred a higher invasive capacity than EGFR in vitro and in vivo. Mechanistically, EGFRvA stimulated expression of STAT3, which upregulated heparin binding EGF (HB-EGF). Reciprocally, HB-EGF stimulated phosphorylation of EGFRvA at Y845 along with STAT3, generating a positive feedback loop that may reinforce invasive function. The significance of EGFRvA expression was reinforced by findings that it is attenuated by miR-542-5p, a microRNA that is a known tumor suppressor. Taken together, our findings define this newfound EGFR isoform as a key theranostic molecule. PMID- 24240703 TI - MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination. AB - Meiotic recombination enables the reciprocal exchange of genetic material between parental homologous chromosomes, and ensures faithful chromosome segregation during meiosis in sexually reproducing organisms. This process relies on the complex interaction of DNA repair factors and many steps remain poorly understood in mammals. Here we report the identification of MEIOB, a meiosis-specific protein, in a proteomics screen for novel meiotic chromatin-associated proteins in mice. MEIOB contains an OB domain with homology to one of the RPA1 OB folds. MEIOB binds to single-stranded DNA and exhibits 3'-5' exonuclease activity. MEIOB forms a complex with RPA and with SPATA22, and these three proteins co-localize in foci that are associated with meiotic chromosomes. Strikingly, chromatin localization and stability of MEIOB depends on SPATA22 and vice versa. Meiob-null mouse mutants exhibit a failure in meiosis and sterility in both sexes. Our results suggest that MEIOB is required for meiotic recombination and chromosomal synapsis. PMID- 24240704 TI - Major trauma: the unseen financial burden to trauma centres, a descriptive multicentre analysis. AB - OBJECTIVE: This research examines the existing funding model for in-hospital trauma patient episodes in New South Wales (NSW), Australia and identifies factors that cause above-average treatment costs. Accurate information on the treatment costs of injury is needed to guide health-funding strategy and prevent inadvertent underfunding of specialist trauma centres, which treat a high trauma casemix. METHODS: Admitted trauma patient data provided by 12 trauma centres were linked with financial data for 2008-09. Actual costs incurred by each hospital were compared with state-wide Australian Refined Diagnostic Related Groups (AR DRG) average costs. Patient episodes where actual cost was higher than AR-DRG cost allocation were examined. RESULTS: There were 16693 patients at a total cost of AU$178.7million. The total costs incurred by trauma centres were $14.7million above the NSW peer-group average cost estimates. There were 10 AR-DRG where the total cost variance was greater than $500000. The AR-DRG with the largest proportion of patients were the upper limb injury categories, many of whom had multiple body regions injured and/or a traumatic brain injury (P<0.001). CONCLUSIONS: AR-DRG classifications do not adequately describe the trauma patient episode and are not commensurate with the expense of trauma treatment. A revision of AR-DRG used for trauma is needed. WHAT IS KNOWN ABOUT THIS TOPIC? Severely injured trauma patients often have multiple injuries, in more than one body region and the determination of appropriate AR-DRG can be difficult. Pilot research suggests that the AR-DRG do not accurately represent the care that is required for these patients. WHAT DOES THIS PAPER ADD? This is the first multicentre analysis of treatment costs and coding variance for major trauma in Australia. This research identifies the limitations of the current AR-DRGS and those that are particularly problematic. The value of linking trauma registry and financial data within each trauma centre is demonstrated. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Further work should be conducted between trauma services, clinical coding and finance departments to improve the accuracy of clinical coding, review funding models and ensure that AR-DRG allocation is commensurate with the expense of trauma treatment. PMID- 24240705 TI - Pollination syndromes ignored: importance of non-ornithophilous flowers to Neotropical savanna hummingbirds. AB - Generalization prevails in flower-animal interactions, and although animal visitors are not equally effective pollinators, most interactions likely represent an important energy intake for the animal visitor. Hummingbirds are nectar-feeding specialists, and many tropical plants are specialized toward hummingbird-pollination. In spite of this, especially in dry and seasonal tropical habitats, hummingbirds may often rely on non-ornithophilous plants to meet their energy requirements. However, quantitative studies evaluating the relative importance of ornithophilous vs. non-ornithophilous plants for hummingbirds in these areas are scarce. We here studied the availability and use of floral resources by hummingbirds in two different areas of the Cerrado, the seasonal savannas in Central Brazil. Roughly half the hummingbird visited plant species were non-ornithophilous, and these contributed greatly to increase the overall nectar availability. We showed that mean nectar offer, at the transect scale, was the only parameter related to hummingbird visitation frequency, more so than nectar offer at single flowers and at the plant scale, or pollination syndrome. Centrality indices, calculated using hummingbird-plant networks, showed that ornithophilous and non-ornithophilous plants have similar importance for network cohesion. How this foraging behaviour affects reproduction of non ornithophilous plants remains largely unexplored and is probably case specific, however, we suggest that the additional energy provided by non-ornithophilous plants may facilitate reproduction of truly ornithophilous flowers by attracting and maintaining hummingbirds in the area. This may promote asymmetric hummingbird plant associations, i.e., pollination depends on floral traits adapted to hummingbird morphology, but hummingbird visitation is determined more by the energetic "reward" than by pollination syndromes. PMID- 24240706 TI - Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata. AB - The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera. PMID- 24240707 TI - De-oncogenic HPV E6/E7 vaccine gets enhanced antigenicity and promotes tumoricidal synergy with cisplatin. AB - In order to develop more effective therapeutic vaccines against cancers with high risk human papillomavirus (HPV) infection, it is crucial to enhance the immunogenicity, eliminate the oncogenicity of oncoproteins, and take a combination of E7- and E6-containing vaccines. It has been shown recently that PE(DeltaIII)-E7-KDEL3 (E7), a fusion protein containing the HPV16 oncoprotein E7 and the translocation domain of Pseudomonas aeruginosa exotoxin A, is effective against TC-1 tumor cells inoculated in mice, therefore, we engineered PE(DeltaIII)-E6-CRL-KDEL3 (E6), the de-oncogenic versions of the E7 and E6 fusion proteins [i.e. PE(DeltaIII)-E7(d)-KDEL3, E7(d), and PE(DeltaIII)-E6(d)-CRL-KDEL3, E6(d)] and tested the immunoefficacies of these fusion proteins as mono- and bivalent vaccines. Results indicated that the E7(d) get higher immunogenicity than its wild type and the E6 fusion proteins augmented the immunogenicity and antitumor effects of their E7 counterparts. Furthermore, the bivalent vaccine system E7(d) plus E6(d), in the presence of cisplatin, showed the best tumoristatic and tumoricidal effects against established tumors in vivo. Therefore, it can be concluded that this novel therapeutic vaccine system, upon further optimization, may shed new light on clinical management of HPV-related carcinomas. PMID- 24240708 TI - Impact of ethnicity, geography, and disease on the microbiota in health and inflammatory bowel disease. AB - BACKGROUND: The gut microbiota is central to health and disorders such as inflammatory bowel disease. Differences in microbiota related to geography and ethnicity may hold the key to recent changes in the incidence of microbiota related disorders. METHODS: Gut mucosal microbiota was analyzed in 190 samples from 87 Caucasian and Chinese subjects, from Australia and Hong Kong, comprising 22 patients with Crohn's disease, 30 patients with ulcerative colitis, 29 healthy controls, and 6 healthy relatives of patients with Crohn's disease. Bacterial 16S rRNA microarray and 454 pyrosequencing were performed. RESULTS: The microbiota was diverse in health, regardless of ethnicity or geography (operational taxonomic unit number and Shannon diversity index). Ethnicity and geography, however, did affect microbial composition. Crohn's disease resulted in reduced bacterial diversity, regardless of ethnicity or geography, and was the strongest determinant of composition. In ulcerative colitis, diversity was reduced in Chinese subjects only, suggesting that ethnicity is a determinant of bacterial diversity, whereas composition was determined by disease and ethnicity. Specific phylotypes were different between health and disease. Chinese patients with inflammatory bowel disease more often than healthy Chinese tended to have had a Western diet in childhood, in the East and West. CONCLUSION: The healthy microbiota is diverse but compositionally affected by geographical and ethnic factors. The microbiota is substantially altered in inflammatory bowel disease, but ethnicity may also play an important role. This may be key to the changing epidemiology in developing countries, and emigrants to the West. PMID- 24240709 TI - Proposal of objective morphological classification system for hepatocellular carcinoma using preoperative multiphase computed tomography. AB - BACKGROUND: To establish a preoperative morphological classification system for hepatocellular carcinoma using multiphase computed tomography. METHODS: All consecutive patients who were diagnosed with hepatocellular carcinoma between 2004 and 2009 were enrolled, for a total of 232 patients. The concavity and convexity of each outer contour of hepatocellular carcinoma acquired from multiphase computed tomography were analyzed, and the area and depth of each indentation were quantified. The indentation area to tumor area ratio (s:S) and the s:S ratio multiplied by the indentation depth to indentation base ratio (s:S * d:t) were used as feature values reflecting the individual shapes. RESULTS: Using a hierarchical cluster analysis, the shapes were classified into three groups: Type I (smooth: n = 158), Type II (jagged: n = 63), and Type III (rough: n = 11). The 5-year survival rates for Types I, II, and III were 64, 53, and 0 %, respectively (I vs. II, P = 0.038; I vs. III, P = 0.001; II vs. III, P = 0.002). The 5-year disease-free survival rates for Types I, II, and III were 27, 23, and 0 %, respectively (I vs. III, P = 0.0003 and II vs. III, P = 0.008). Microscopic portal venous invasion was significantly more likely with Type III than with Type I or II (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: The newly developed semiautomatic computed tomography-based morphological classification system appears to provide a promising additional criterion for the prognostic categorization of patients with hepatocellular carcinoma. PMID- 24240713 TI - A patient with POEMS syndrome: the pathology of glomerular microangiopathy. AB - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is potentially fatal multisystem disorder but its renal complication has often been overlooked because renal involvement is not necessarily included in the diagnostic criteria of POEMS. This report documents the patient with POEMS syndrome with long-term renal histopathological changes evaluated by renal biopsy. A 32-year-old Japanese woman presented with symptoms consistent with POEMS syndrome associated with proteinuria and IgA-lambda type monoclonal gammopathy. Initial renal biopsy for confirmation of diagnosis revealed the proliferation of glomerular capillary loops located in the expanded mesangial matrices associated with glomerular enlargement. Electron microscopy examination of the renal biopsy revealed the presence of double contoured glomerular basement membrane containing peculiar fibrillary structure. The patient was therefore initially diagnosed as membranoproliferative glomerulonephritis (MPGN)-like lesion without any significant immunoglobulins and complements deposition. The patient was subsequently admitted to hospital on five occasions due to renal dysfunction and anasarca for the next four years of her clinical course. The severity of anasarca was correlated mainly with serum titer of vascular endothelial growth factor (VEGF) during this period. Acute renal failure occurred at the last admission and the second biopsy was performed. An increased mesangial matrix and frequent global sclerosis of the glomeruli with arteriolosclerosis was noted in this second biopsy compared to the first one. These findings of renal biopsies suggest that the glomerular microangiopathy of POEMS syndrome may occur in the context of systemic capillary leak syndrome superimposed on chronic endothelial injury. PMID- 24240712 TI - Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. AB - IMPORTANCE: Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE: To determine whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4 degrees C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES: The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS: The intervention decreased mean core temperature by 1.20 degrees C (95% CI, -1.33 degrees C to -1.07 degrees C) in patients with VF and by 1.30 degrees C (95% CI, -1.40 degrees C to -1.20 degrees C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34 degrees C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% [95% CI, 57.0%-68.0%] vs 64.3% [95% CI, 58.6%-69.5%], respectively; P = .69) and among patients without VF (19.2% [95% CI, 15.6%-23.4%] vs 16.3% [95% CI, 12.9%-20.4%], respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% [95% CI, 51.8%-63.1%] of cases had full recovery or mild impairment vs 61.9% [95% CI, 56.2%-67.2%] of controls; P = .69) or those without VF (14.4% [95% CI, 11.3%-18.2%] of cases vs 13.4% [95% CI,10.4%-17.2%] of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% [95% CI, 22% 29%] vs 21% [95% CI, 18%-24%], respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE: Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34 degrees C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00391469. PMID- 24240716 TI - Estimation of body postures on bed using unconstrained ECG measurements. AB - We developed and tested a system for estimating body postures on a bed using unconstrained measurements of electrocardiogram (ECG) signals using 12 capacitively coupled electrodes and a conductive textile sheet. Thirteen healthy subjects participated in the experiment. After detecting the channels in contact with the body among the 12 electrodes, the features were extracted on the basis of the morphology of the QRS (Q wave, R wave, and S wave of ECG) complex using three main steps. The features were applied to linear discriminant analysis, support vector machines with linear and radial basis function (RBF) kernels, and artificial neural networks (one and two layers), respectively. SVM with RBF kernel had the highest performance with an accuracy of 98.4% for estimation of four body postures on the bed: supine, right lateral, prone, and left lateral. Overall, although ECG data were obtained from few sensors in an unconstrained manner, the performance was better than the results that have been reported to date. The developed system and algorithm can be applied to the obstructive apnea detection and analyses of sleep quality or sleep stages, as well as body posture detection for the management of bedsores. PMID- 24240717 TI - Use of electromyographic and electrocardiographic signals to detect sleep bruxism episodes in a natural environment. AB - Diagnosis of bruxism is difficult since not all contractions of masticatory muscles during sleeping are bruxism episodes. In this paper, we propose the use of both EMG and ECG signals for the detection of sleep bruxism. Data have been acquired from 21 healthy volunteers and 21 sleep bruxers. The masseter surface EMGs were detected with bipolar concentric electrodes and the ECG with monopolar electrodes located on the clavicular regions. Recordings were made at the subjects' homes during sleeping. Bruxism episodes were automatically detected as characterized by masseter EMG amplitude greater than 10% of the maximum and heart rate increasing by more than 25% with respect to baseline within 1 s before the increase in EMG amplitude above the 10% threshold. Furthermore, the subjects were classified as bruxers and nonbruxers by a neural network. The number of bruxism episodes per night was 24.6 +/- 8.4 for bruxers and 4.3 +/- 4.5 for controls ( P < 0.0001). The classification error between bruxers and nonbruxers was 1% which was substantially lower than when using EMG only for the classification. These results show that the proposed system, based on the joint analysis of EMG and ECG, can provide support for the clinical diagnosis of bruxism. PMID- 24240718 TI - An online one class support vector machine-based person-specific fall detection system for monitoring an elderly individual in a room environment. AB - In this paper, we propose a novel computer vision-based fall detection system for monitoring an elderly person in a home care, assistive living application. Initially, a single camera covering the full view of the room environment is used for the video recording of an elderly person's daily activities for a certain time period. The recorded video is then manually segmented into short video clips containing normal postures, which are used to compose the normal dataset. We use the codebook background subtraction technique to extract the human body silhouettes from the video clips in the normal dataset and information from ellipse fitting and shape description, together with position information, is used to provide features to describe the extracted posture silhouettes. The features are collected and an online one class support vector machine (OCSVM) method is applied to find the region in feature space to distinguish normal daily postures and abnormal postures such as falls. The resultant OCSVM model can also be updated by using the online scheme to adapt to new emerging normal postures and certain rules are added to reduce false alarm rate and thereby improve fall detection performance. From the comprehensive experimental evaluations on datasets for 12 people, we confirm that our proposed person-specific fall detection system can achieve excellent fall detection performance with 100% fall detection rate and only 3% false detection rate with the optimally tuned parameters. This work is a semiunsupervised fall detection system from a system perspective because although an unsupervised-type algorithm (OCSVM) is applied, human intervention is needed for segmenting and selecting of video clips containing normal postures. As such, our research represents a step toward a complete unsupervised fall detection system. PMID- 24240719 TI - Fuzzy reasoning of accident provenance in pervasive healthcare monitoring systems. AB - In pervasive healthcare monitoring environments, data provenance, as one metadata, can help people analyze the reasons for medical accidents that are generated by complex events. This reasoning processing often encounters inaccurate time and irreversible reasoning problems. How to solve the uncertain process and fuzzy transformation time presents many challenges to the study of data provenance. In this paper, we propose a backward derivation model with the provenance semantic, backward fuzzy time reasoning net (BFTRN), to solve these two problems. We design a backward reasoning algorithm motivated by time automation theory based on this model. With regard to given life-critical alarms and some constraints, it cannot only derive all evolution paths and the possibility distribution of paths from historical information, but also efficiently compute the value of fuzzy time function for each transition of lift critical complex alarms in the healthcare monitoring system. We also analyze the properties of BFTRN model in this paper. Experiments on real dataset show that the proposed model is efficient. PMID- 24240720 TI - A pervasive assessment of motor function: a lightweight grip strength tracking system. AB - With the growing cost associated with the diagnosis and treatment of chronic neuro-degenerative diseases, the design and development of portable monitoring systems becomes essential. Such portable systems will allow for early diagnosis of motor function ability and provide new insight into the physical characteristics of ailment condition. This paper introduces a highly mobile and inexpensive monitoring system to quantify upper-limb performance for patients with movement disorders. With respect to the data analysis, we first present an approach to quantify general motor performance using the introduced sensing hardware. Next, we propose an ailment-based analysis which employs a significant feature identification algorithm to perform cross-patient data analysis and classification. The efficacy of the proposed framework is demonstrated using real data collected through a clinical trial. The results show that the system can be utilized as a preliminary diagnostic tool to inspect the level of hand-movement performance. The ailment-based analysis performs an intergroup comparison of physiological signals for cerebral vascular accident (CVA) patients, chronic inflammatory demyelinating polyneuropathy (CIDP) patients, and healthy individuals. The system can classify each patient group with an accuracy of up to 95.00% and 91.42% for CVA and CIDP, respectively. PMID- 24240721 TI - Automatic tracking of aponeuroses and estimation of muscle thickness in ultrasonography: a feasibility study. AB - Muscle thickness measurement in ultrasonography was traditionally conducted by a trained operator, and the manual detecting process is time consuming and subjective. In this paper, we proposed an automatic tracking strategy to achieve the continuous and quantitative measurement for gastrocnemius muscle thickness in ultrasound images. The method involved three steps: tracking of seed points, contours extraction of aponeuroses, and muscle thickness estimation. In an ultrasound image sequence, we first selected two seed points in the first frame manually for the superficial and deep aponeuroses, respectively. Seed points in all following frames were then tracked by registering to their respective previous frames. Second, we adopted the local and global intensity fitting model to extract the contours of aponeuroses. At last, the muscle thickness was achieved by calculating the distance between the contours of superficial and deep aponeuroses. The performance of the algorithm was evaluated using 500 frames of ultrasound images. It was demonstrated in the experiments that the proposed methods could be used for objective tracking of aponeuroses and estimation of muscle thickness in musculoskeletal ultrasound images. PMID- 24240722 TI - Diagnosis of early Alzheimer's disease based on EEG source localization and a standardized realistic head model. AB - In this paper, distributed electroencephalographic (EEG) sources in the brain have been mapped with the objective of early diagnosis of Alzheimer's disease (AD). To this end, records from a montage of a high-density EEG from 17 early AD patients and 17 matched healthy control subjects were considered. Subjects were in eyes-closed, resting-state condition. Cortical EEG sources were modeled by the standardized low-resolution brain electromagnetic tomography (sLORETA) method. Relative logarithmic power spectral density values were obtained in the four conventional frequency bands (alpha, beta, delta, and theta) and 12 cortical regions. Results show that in the left brain hemisphere, the theta band of AD subjects shows an increase in the power, whereas the alpha band shows a decreased activity (P-value <0.05). In the right brain hemisphere of AD subjects, a decreased activity is observed in all frequency bands. It was also noticed that the right temporal region shows a significant difference between the two groups in all frequency bands. Using a support vector machine, control and patient groups are discriminated with an accuracy of 84.4%, sensitivity 75.0%, and specificity of 93.7%. PMID- 24240723 TI - Hardware-efficient low-power image processing system for wireless capsule endoscopy. AB - This paper presents the design of a hardware-efficient, low-power image processing system for next-generation wireless endoscopy. The presented system is composed of a custom CMOS image sensor, a dedicated image compressor, a forward error correction (FEC) encoder protecting radio transmitted data against random and burst errors, a radio data transmitter, and a controller supervising all operations of the system. The most significant part of the system is the image compressor. It is based on an integer version of a discrete cosine transform and a novel, low complexity yet efficient, entropy encoder making use of an adaptive Golomb-Rice algorithm instead of Huffman tables. The novel hardware-efficient architecture designed for the presented system enables on-the-fly compression of the acquired image. Instant compression, together with elimination of the necessity of retransmitting erroneously received data by their prior FEC encoding, significantly reduces the size of the required memory in comparison to previous systems. The presented system was prototyped in a single, low-power, 65 nm field programmable gate arrays (FPGA) chip. Its power consumption is low and comparable to other application-specific-integrated-circuits-based systems, despite FPGA-based implementation. PMID- 24240724 TI - A watermarking-based medical image integrity control system and an image moment signature for tampering characterization. AB - In this paper, we present a medical image integrity verification system to detect and approximate local malevolent image alterations (e.g., removal or addition of lesions) as well as identifying the nature of a global processing an image may have undergone (e.g., lossy compression, filtering, etc.). The proposed integrity analysis process is based on nonsignificant region watermarking with signatures extracted from different pixel blocks of interest, which are compared with the recomputed ones at the verification stage. A set of three signatures is proposed. The first two devoted to detection and modification location are cryptographic hashes and checksums, while the last one is issued from the image moment theory. In this paper, we first show how geometric moments can be used to approximate any local modification by its nearest generalized 2-D Gaussian. We then demonstrate how ratios between original and recomputed geometric moments can be used as image features in a classifier-based strategy in order to determine the nature of a global image processing. Experimental results considering both local and global modifications in MRI and retina images illustrate the overall performances of our approach. With a pixel block signature of about 200 bit long, it is possible to detect, to roughly localize, and to get an idea about the image tamper. PMID- 24240725 TI - Fully unsupervised M-FISH chromosome image characterization. AB - Chromosome analysis is an important and difficult task for clinical diagnosis and biological research. A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, ...,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods. Since the developed classification method does not require training data, it is highly convenient when ground truth does not exist. PMID- 24240726 TI - Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy. AB - PURPOSE: To investigate the expression and clinical significance of CADM2 in hepatocellular carcinomas (HCC). METHODS: The level of expression of CADM2 mRNA was assessed in frozen tumor specimens and adjacent noncancerous tissues from 30 HCC patients by real-time PCR. The protein level was determined by immunohistochemistry on a tissue microarray containing tumor and adjacent noncancerous tissues from 234 HCC patients. Clinicopathological characteristics associated analysis was performed through SPSS18 . RESULTS: CADM2 was strikingly down regulated in HCC. CADM2 expression was associated with differentiation (P = 0.000), serum alpha-fetoprotein (P = 0.003), vascular invasion (P = 0.001), and hepatitis B surface antigen (HBsAg, P = 0.038). Furthermore, patients with low CADM2 expression had significantly poorer recurrence-free survival (RFS) (40.8 and 34.2 % vs. 56.3 and 50.1 % in 3- and 5-year RFS, respectively, P = 0.005). Subgroup analysis revealed that the difference in RFS between groups with low- and high-CADM2 expression still existed among patients belonging to stage 0 or A of BCLC staging system (P = 0.008), patients with tumor <=5 cm in size (P = 0.013), and alpha-fetoprotein-negative patients (P = 0.003). Moreover, low expression was more frequently observed in the early recurrence group (within 2 years, P = 0.007). Further multivariate Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence. CONCLUSION: CADM2 serves as a novel predictor of RFS in HCC patients after curative resection. PMID- 24240727 TI - Toxicology testing in fatally injured workers: a review of five years of Iowa FACE cases. AB - Toxicology testing of fatally injured workers is not routinely conducted. We completed a case-series study of 2005-2009 occupational fatalities captured by Iowa's Fatality Assessment and Control Evaluation (FACE) Program. The goals of our research were to: (1) measure the proportion of FACE cases that undergo toxicology testing, and describe the factors associated with being tested, and (2) measure the rate of positive toxicology tests, the substances identified and the demographics and occupations of victims who tested positive. Case documents and toxicology laboratory reports were reviewed. There were 427 occupational deaths from 2005 to 2009. Only 69% underwent toxicology testing. Younger workers had greater odds of being tested. Among occupational groups, workers in farming, fishing and forestry had half the odds of being tested compared to other occupational groups. Of the 280 cases with toxicology tests completed, 22% (n = 61) were found to have positive toxicology testing. Commonly identified drug classes included cannabinoids and alcohols. Based on the small number of positive tests, older victims (65+ years) tested positive more frequently than younger workers. Management, business, science, arts, service and sales/office workers had proportionately more positive toxicology tests (almost 30%) compared with other workers (18-22%). These results identify an area in need of further research efforts and a potential target for injury prevention strategies. PMID- 24240728 TI - Methods for recovering microorganisms from solid surfaces used in the food industry: a review of the literature. AB - Various types of surfaces are used today in the food industry, such as plastic, stainless steel, glass, and wood. These surfaces are subject to contamination by microorganisms responsible for the cross-contamination of food by contact with working surfaces. The HACCP-based processes are now widely used for the control of microbial hazards to prevent food safety issues. This preventive approach has resulted in the use of microbiological analyses of surfaces as one of the tools to control the hygiene of products. A method of recovering microorganisms from different solid surfaces is necessary as a means of health prevention. No regulation exists for surface microbial contamination, but food companies tend to establish technical specifications to add value to their products and limit contamination risks. The aim of this review is to present the most frequently used methods: swabbing, friction or scrubbing, printing, rinsing or immersion, sonication and scraping or grinding and describe their advantages and drawbacks. The choice of the recovery method has to be suitable for the type and size of the surface tested for microbiological analysis. Today, quick and cheap methods have to be standardized and especially easy to perform in the field. PMID- 24240730 TI - Acute compartment syndrome after extracorporeal membrane oxygenation. PMID- 24240729 TI - Cardiac myosin-binding protein C: hypertrophic cardiomyopathy mutations and structure-function relationships. AB - Cardiac myosin-binding protein C (cMyBP-C) research has been characterized by two waves. Initial interest was piqued by its discovery in 1973 as a contaminant of myosin preparations from skeletal muscle. The second wave started in 1995 by the discovery that mutations in the gene encoding cMyBP-C cause hypertrophic cardiomyopathy (HCM). In this review, we will address what is known of cMyBP-C's role as a regulator of contraction as well as its role in HCM. PMID- 24240731 TI - Left ventricular assist device management in the ICU. AB - OBJECTIVES: To review left ventricular assist device physiology, initial postoperative management, common complications, trouble shooting and management of hypotension, and other common ICU problems. DATA SOURCE: Narrative review of relevant medical literature. DATA SYNTHESIS: Left ventricular assist devices prolong the lives of patients with end-stage heart failure, and their use is increasing. Continuous-flow left ventricular assist devices have replaced first generation pulsatile devices. These patients present unique management concerns. In the immediate postimplant period, care must be taken to support the unassisted right ventricle. Invasive monitors for blood pressure, pulmonary artery catheterization, and echocardiography are essential to optimize left ventricular assist device settings and cardiac performance. Anticoagulation is necessary to prevent devastating thrombotic and embolic complications, but bleeding is a major source of morbidity due to inherent bleeding diatheses and prescribed anticoagulants. Infection of the device can be life threatening, and all infections must be aggressively treated to avoid seeding the device. Patients are at risk of ventricular arrhythmias because of their underlying disease, as well as the placement and position of the inflow cannula. Aortic valve stenosis and insufficiency develop over time and can lead to thrombosis or heart failure. Cardiopulmonary resuscitation with chest compressions must be performed with care or not at all due to risk of dislodging the device. CONCLUSION: Intensivists are increasingly likely to encounter patients requiring mechanical circulatory support with left ventricular assist devices at various points in the trajectory of their disease, from the immediate postimplant period to subsequent admissions for complications, and at end of life. A basic understanding of left ventricular assist device physiology is essential to the safe and effective care of these patients. PMID- 24240732 TI - Beyond newborn survival: the world you are born into determines your risk of disability-free survival. PMID- 24240734 TI - Systems biology of primary CNS lymphoma: from genetic aberrations to modeling in mice. AB - Primary lymphoma of the central nervous system (CNS, PCNSL) is a specific diffuse large B cell lymphoma entity arising in and confined to the CNS. Despite extensive research since many decades, the pathogenetic mechanisms underlying the remarkable tropism of this peculiar malignant hematopoietic tumor remain still to be elucidated. In the present review, we summarize the present knowledge on the genotypic and phenotypic characteristics of the tumor cells of PCNSL, give an overview over deregulated molecular pathways in PCNSL and present recent progress in the field of preclinical modeling of PCNSL in mice. With regard to the phenotype, PCNSL cells resemble late germinal center exit IgM+IgD+ B cells with blocked terminal B cell differentiation. They show continued BCL6 activity in line with ongoing activity of the germinal center program. This together with the pathways deregulated by genetic alterations may foster B cell activation and brisk proliferation, which correlated with the simultaneous MYC and BCL2 overexpression characteristic for PCNSL. On the genetic level, PCNSL are characterized by ongoing aberrant somatic hypermutation that, besides the IG locus, targets the PAX5, TTF, MYC, and PIM1 genes. Moreover, PCNSL cells show impaired IG class switch due to sMU region deletions, and PRDM1 mutations. Several important pathways, i.e., the B cell receptor (BCR), the toll-like receptor, and the nuclear factor-kappaB pathway, are activated frequently due to genetic changes affecting genes like CD79B, SHIP, CBL, BLNK, CARD11, MALT1, BCL2, and MYD88. These changes likely foster tumor cell survival. Nevertheless, many of these features are also present in subsets of systemic DLBLC and might not be the only reasons for the peculiar tropism of PCNSL. Here, preclinical animal models that closely mimic the clinical course and neuropathology of human PCNSL may provide further insight and we discuss recent advances in this field. Such models enable us to understand the pathogenetic interaction between the malignant B cells, resident cell populations of the CNS, and the associated inflammatory infiltrate. Indeed, the immunophenotype of the CNS as well as tumor cell characteristics and intracerebral interactions may create a micromilieu particularly conducive to PCNSL that may foster aggressiveness of tumor cells and accelerate the fatal course of disease. Suitable animal models may also serve as a well-defined preclinical system and may provide a useful tool for developing new specific therapeutic strategies. PMID- 24240736 TI - Neuropathology of cigarette smoking. AB - It is well established that cigarette smoking is hazardous to health and is a risk factor for many chronic diseases. However, its impact on the brain, whether it be from prenatal exposure to maternal cigarette smoking, cerebrovascular disease, Alzheimer's disease (AD) or Parkinson's disease, is still not very clear. Neuroimaging and neuropathological investigations suggest that there are heterogeneous effects of cigarette smoking on the brain. On the one hand, it is quite clear that cigarette smoking causes damage to endothelial cells, resulting in increased risk of cerebrovascular disease. On the other hand, it seems to be associated with different Alzheimer's pathologies in post-mortem brains and experimental models, despite the fact that epidemiological studies clearly indicate a positive correlation between cigarette smoking and increased risk for AD. Interestingly, cigarette smoking appears to be associated with reduced Parkinson's pathology in post-mortem brains. However, although nicotine in cigarettes may have some neuroprotective actions, the effects of all the other toxic compounds in cigarettes cannot be ignored. It is, therefore, our aim to summarize what is known about the neuropathology of cigarette smoking and, in particular, its implications for neurodegenerative diseases. PMID- 24240735 TI - The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid neuroinflammatory cascade. AB - Pro-inflammatory S100A9 protein is increasingly recognized as an important contributor to inflammation-related neurodegeneration. Here, we provide insights into S100A9 specific mechanisms of action in Alzheimer's disease (AD). Due to its inherent amyloidogenicity S100A9 contributes to amyloid plaque formation together with Abeta. In traumatic brain injury (TBI) S100A9 itself rapidly forms amyloid plaques, which were reactive with oligomer-specific antibodies, but not with Abeta and amyloid fibrillar antibodies. They may serve as precursor-plaques for AD, implicating TBI as an AD risk factor. S100A9 was observed in some hippocampal and cortical neurons in TBI, AD and non-demented aging. In vitro S100A9 forms neurotoxic linear and annular amyloids resembling Abeta protofilaments. S100A9 amyloid cytotoxicity and native S100A9 pro-inflammatory signaling can be mitigated by its co-aggregation with Abeta, which results in a variety of micron scale amyloid complexes. NMR and molecular docking demonstrated transient interactions between native S100A9 and Abeta. Thus, abundantly present in AD brain pro-inflammatory S100A9, possessing also intrinsic amyloidogenic properties and ability to modulate Abeta aggregation, can serve as a link between the AD amyloid and neuroinflammatory cascades and as a prospective therapeutic target. PMID- 24240738 TI - Relationship between contents of leucoanthocyanidin and dhurrin in sorghum leaves. AB - Flag leaves of 'Colman' forage sorghum (Sorghum bicolor) contain at least 25 times as much leucoanthocyanidin (LAC) and approximately half as much of the cyanogenic glucoside, dhurrin, as do flag leaves of 'White Collier' forage sorghum. Assays of flag leaves from 119 F2 plants and 11 F5 lines from crosses between these two cultivars revealed a statistically significant negative association between levels of LAC and dhurrin. Both LAC and dhurrin are aromatic compounds, and the negative association between the two may be the result of competition for intermediates or products of the aromatic biosynthetic pathway. This rationale appears to be quite different from that for the negative association reported for levels of tannin and cyanide in Lotus corniculatus. Although the negative relationship between LAC and dhurrin in sorghum was statistically significant, the association was not consistent enough to suggest that either trait could be used reliably in selecting or breeding to modify the other trait. PMID- 24240737 TI - Staging TDP-43 pathology in Alzheimer's disease. AB - TDP-43 immunoreactivity occurs in 19-57 % of Alzheimer's disease (AD) cases. Two patterns of TDP-43 deposition in AD have been described involving hippocampus (limbic) or hippocampus and neocortex (diffuse), although focal amygdala involvement has been observed. In 195 AD cases with TDP-43, we investigated regional TDP-43 immunoreactivity with the aim of developing a TDP-43 in AD staging scheme. TDP-43 immunoreactivity was assessed in amygdala, entorhinal cortex, subiculum, hippocampal dentate gyrus, occipitotemporal, inferior temporal and frontal cortices, and basal ganglia. Clinical, neuroimaging, genetic and pathological characteristics were assessed across stages. Five stages were identified: stage I showed scant-sparse TDP-43 in the amygdala only (17 %); stage II showed moderate-frequent amygdala TDP-43 with spread into entorhinal and subiculum (25 %); stage III showed further spread into dentate gyrus and occipitotemporal cortex (31 %); stage IV showed further spread into inferior temporal cortex (20 %); and stage V showed involvement of frontal cortex and basal ganglia (7 %). Cognition and medial temporal volumes differed across all stages and progression across stages correlated with worsening cognition and medial temporal volume loss. Compared to 147 AD patients without TDP-43, only the Boston Naming Test showed abnormalities in stage I. The findings demonstrate that TDP-43 deposition in AD progresses in a stereotypic manner that can be divided into five distinct topographic stages which are supported by correlations with clinical and neuroimaging features. Given these findings, we recommend sequential regional TDP-43 screening in AD beginning with the amygdala. PMID- 24240739 TI - Characterization of biomass production, cytology and phenotypes of plants regenerated from embryogenic callus cultures of Pennisetum americanum x P. purpureum (hybrid triploid napiergrass). AB - Five hundred and twenty-four plants of a triploid, sexually sterile hybrid napiergrass (Pennisetum americanum x P. purpureum; 3x=21) were regenerated from embryogenic callus cultures obtained from segments of young inflorescences. Replicated field trials were conducted for two consecutive years to compare the biomass yield, phenotype and cytology of tissue culture regenerants (TC) and vegetatively propagated (V) plants. In the first year total biomass yield of TC plants was significantly greater than V plants but there was no significant difference in the second year. TC plants had more tillers compared to V plants. V plants did not show any morphological variability. The TC population also exhibited a high degree of phenotypic stability (96%). There were 23 phenotypic variants in the TC population of 524, most of them being more dwarf and late flowering. Detailed morphological analysis of the TC-variant plants suggests that they very likely arose from only a few variant cell lines. Cytological analysis indicated stability of the triploid status in randomly selected regenerants. Two of the morphological variants were hexaploids (6x=42). It is concluded that embryogenic callus cultures can provide useful alternative for the rapid propagation of hybrid napier-grass which is commonly propagated by cuttings. PMID- 24240740 TI - Transformation of cucumber (Cucumis sativus L.) plants with Agrobacterium rhizogenes. AB - Transgenic cucumber plants (Cucumis sativus L., cv. 'Straight Eight') were regenerated from roots induced by inoculation of inverted hypocotyl sections with Agrobacterium rhizogenes containing the vector pARC8 in addition to the resident Ri-plasmid. The DNA transferred to the plant from the vector (T-DNA) included a gene which encoded the enzyme neomycin phosphotransferase II, and thus conferred on the plant cells resistance to kanamycin. The transgenic plants looked normal and were positive for the neomycin phosphotransferase II. Southern blot analysis of the transgenic plants revealed that all plants contained vector DNA, but only some of them contained DNA from the Ri plasmid. PMID- 24240741 TI - Haploid and diploid plant regeneration from protoplasts of anther callus in rice. AB - The regeneration of haploid and diploid plants was demonstrated from protoplasts that were isolated from cell suspensions of anther callus in rice. The cell suspension in the AA medium that contained 4 amino acids as the sole nitrogen source was friable, finely dispersed, and readily released a large number of protoplasts. These protoplasts, subsequently cultured in NO3 medium that contained nitrate as the sole nitrogen source, formed compact calli. The compact calli produced green plants with a frequency of 24%. Out of 15 flowering plants, 4 were haploids, the others were diploids which showed a uniform morphology but varied in seed fertility from 95 to 0%. PMID- 24240742 TI - Nuclear DNA changes within Helianthus annuus L.: cytophotometric, karyological and biochemical analyses. AB - Cytophotometric measurement of the root meristems of seedlings after Feulgen staining reveals that large differences (up to 58.16%) in nuclear DNA content may occur in the thirty-one cultivated varieties or lines of Helianthus annuus tested. Significant variations (not exceeding 25%) in the amount of DNA, which does not differ between the root and the shoot meristems of a single seedling, are also found to exist within cultivars or lines; even seedlings obtained from seeds collected from different portions of single heads of plants belonging to a selfed line may vary one from the other in this respect. Variations in the number of chromosomes or alterations in the chromosome structure do not account for the differences observed in nuclear DNA content. Karyometric analyses demonstrate that the surface area of squashed interphase nuclei and metaphase chromosomes and the total length of the latter increase with the increase in Feulgen/DNA absorption. DNA thermal denaturation and reassociation kinetics indicate that a frequency variation in repeated DNA sequences goes hand in hand with changes in the size of the genome. These results, supporting the concept that a plant genome is highly flexible, are discussed in relation to other data to be found in the literature on the intraspecific variation in the nuclear DNA content and in relation to the way in which it is produced in H. annuus. PMID- 24240743 TI - A comparison between the full diallel cross and the simplified triple-test cross. AB - The simplified triple-test cross (sTTC) is a mating design that, because of its economic use of the experimental material as compared with other designs, seems very attractive. In theory, its power is almost equal to that of more elaborate designs such as the diallel cross. To evaluate the merits of both designs in a genetic analysis of mouse behavior, the results of a previous replicated 4*4 diallel cross (Crusio and van Abeelen 1986) were reanalyzed as a sTTC. We found that, at least with the fairly low number of strains employed, the sTTC analysis is clearly inferior to the diallel cross. This finding, in combination with some theoretical considerations, leads to the conclusion that the sTTC design is not a very useful one for such studies. PMID- 24240744 TI - Characterization and localization of cryptic satellite DNAs in barley (Hordeum vulgare). AB - Three satellites on the heavy side of the main band and two satellites on the light side were isolated in a pure from by preparative ultracentrifugation of H. vulgare DNA in Ag(+)/Cs2SO4 density gradients. The satellites were characterised in terms of their buoyant densities in CsCl and their thermal dissocation temperature in both native and reassociated forms to Cot 4. In CsCl gradients, heavy satellites formed a single peak whereas light satellites resolved into more than one component. Thermal transitions of some satellites indicated the presence of more than one molecular species. The multicomponent nature of thermal denaturation profiles was evident on differential analysis. Radioactive RNAs complementary to the three heavy satellites of H. vulgare were localised by in situ hybridization onto its nuclei and chromosomes. One heavy satellite (H3) was found to be distributed on all chromosomes, although one pair showed less hybridization compared to the others. The other satellite (H1) appeared to be present in a much lower amount on the chromosomes. PMID- 24240745 TI - Analysis and in situ hybridization of cryptic satellites in Hordeum arizonicum. AB - Three satellites, one (H1) on the heavy side of the main band of Hordeum arizonicum DNA and two (L1, L2) on the lighter side were purified using preparative silver-cesium sulphate density gradients. The native and the reassociated satellite DNAs were analysed in terms of buoyant densities and thermal dissociation. In cesium chloride gradients the H1 and L1 satellites formed single peaks corresponding to buoyant densities of 1.700 and 1.701 g . cm( 3) respectively while the L2 satellite gave two peaks (1.680 and 1.661 g . cm( 3)). The H1 satellite showed three thermal components (Tm=82.5 degrees C, 87 degrees C and 91.5 degrees C) while the L1 and L2 had three (86.5, 92, 97.5 degrees C) and two (86, 95 degrees C) respectively. The H1 satellite was localized on the nuclei and chromosomes. The distribution of H1 onto approximately on third of the complement may reflect the genome specific origin of this satellite. PMID- 24240746 TI - Pollen gene expression analysed by micro-isoelectric focusing of proteins from isolated pollen grains in Cucurbita pepo L. AB - Isoelectric focusing of proteins from single pollen grains of Cucurbita pepo L. has been developed for large scale study of pollen grain populations' heterogeneity. Forty to forty-five protein bands from one pollen grain are revealed after silver staining. Applications of this technique to pollen grain populations from different genotypes are described in this paper. Possible applications and limits of this technique are discussed with respect to plant breeding especially for the measure of gene frequencies in pollen grain populations. PMID- 24240747 TI - Theoretical studies on the necessary number of components in mixtures : 4. Number of components and juvenile-mature correlations. AB - Theoretical studies on the necessary numbers of components in mixtures (for example multiclonal varieties or mixtures of lines) have been performed according to the relations between the juvenile-mature correlations of mixtures and their number of components. For the juvenile-mature correlation rE based upon the values of the single components (= component means at juvenile and mature ages) and the juvenile-mature correlation rM based upon the means of mixtures of different components we usually will have rM>rE. Furthermore, rM will increase with an increasing number of components in the mixtures. The effectiveness of an early selection will be mainly determined by the magnitude of the juvenile-mature correlation. If we have rM>rE an improvement of early testing can be realized by using mixtures instead of single components. But, what are the necessary numbers of components so that rM will be sufficiently high to enable an effective early selection of mixtures? Some relations between rE and rM can be obtained and conclusions have been derived.The statistical approach 'significant difference between rE and rM for a given numerical value of rM' leads to estimates for the necessary number n of components dependent on rM, alpha, rE and N where: N = total number of components, which are available for the composition of mixtures and alpha = error probability. For different tree species rE can be estimated by an appropriate formula which depends on T with T = time (in years) from planting date until the mature age.Lambeth's formula, for example, has been developed for height growth in pines. For this situation numerical calculations are performed using rM=0.90 and alpha=0.05. The necessary numbers n for T=5, T=10, T=20 and T=50 are: 6, 9, 10 and 12 (for N=50); 13, 17, 20 and 23 (for N=100); 26, 34, 40 and 46 (for N=200); 38, 51, 60 and 69 (for N=300); 64, 85, 100 and 114 (for N=500) and 128, 171, 199 and 228 (for N=1,000). The dependence of these necessary numbers n of components on different type I errors alpha and different levels of rM have been investigated numerically. PMID- 24240748 TI - Growth to sexual maturity of dwarf and nondwarf White Rock chickens divergently selected for juvenile body weight. AB - Growth from hatching to the onset of lay (sexual maturity) was studied in White Plymouth Rock pullets from lines selected for high (HN) and low (LN) 56-day body weight, their reciprocal F1 crosses, an F2 cross, and two dwarf populations originating from the HN and LN parental lines. The highest R(2)s for describing growth for all populations except HN were obtained when body weight was expressed relative to body weight at sexual maturity. Modes of inheritance differed depending on whether patterns of growth were expressed in a chronological time frame or on a physiological basis. Heterosis observed for age at sexual maturity and for body weight after the age when selection was made was not in evidence when ages and weights were expressed as a proportion of those at sexual maturity. PMID- 24240749 TI - Chromosomal alterations in the karyotype of triticale in comparison with the parental forms : 2. Heterochromatin of the wheat chromosomes. AB - Wheat chromosomes of the primary winter hexaploid and octoploid triticales and of the parental durum and common wheat varieties were studied using morphometric analysis. The size of some heterochromatic segments was shown to change in triticale. Telomeric and intercalary C-bands both increased and decreased in size whereas centromeric bands only increased. The size variability of C-bands in triticale B-genome chromosomes decreased in most of the cases and increased only for several specific C-bands. The C-bands of homologous B-genome chromosomes changed in the same direction in both triticale forms. The changes in size of the C-bands found in R-genome chromosomes detected earlier in these triticale forms (Badaeva et al. 1986) were shown to coincide in their pattern with the size changes of C-bands in homeological B-genome chromosomes. Our data are indicative of regular, directed chromosomal changes in the triticale karyotype. PMID- 24240750 TI - Recombination and genome size. AB - Within complements the chiasma frequency per chromosome, which directly reflects the amount of recombination, is generally closely correlated with chromosome length, i.e. the chromosomal DNA content. The correlation does not apply when comparisons are made between the complements of different species. Analyses of results from three Angiosperm genera show a progressive decrease in the chiasma frequency per picogram of DNA with increase in nuclear DNA amount. PMID- 24240751 TI - The search for hidden enzymatic variation in the aphid Macrosiphum rosae (L.). AB - Using two different buffer systems and up to 6 different electrophoretic polyacrylamide gel concentrations, hidden enzymatic variability was investigated in samples of the rose aphid Macrosiphum rosae. MDH1, PGM1, SDH, EST and LAP were found to be polymorphic. No additional variation was observed by changing the test conditions compared to those of earlier investigations using starch gel electrophoresis. PMID- 24240752 TI - Variation and inheritance of the arachin polypeptides of groundnut (Arachis hypogaea L.). AB - Variation in the arachin polypeptides of groundnut genotypes was observed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Three regions could be observed on the electropherogram. Region 1, corresponding to conarachin, did not show any variation; region 2, consisting of arachin acidic subunits, showed variation; region 3, containing the arachin basic subunits, did not show any variation. There are four varietal classes of arachin polypeptide patterns: class A comprised three acidic subunits of arachin of molecular weights 47.5, 45.1 and 42.6 kd and a basic subunit of 21.4 kd; class B, with three acidic subunits of molecular weights 47.5, 45.1 and 41.2 kd and a basic subunit of 21.4 kd; class C of an additive pattern of class A and class B; class D, of two acidic polypeptides of 47.5, 45.1 kd and the basic 21.4 kd subunit. Of the 90 genotypes studied, 73% belong to class A, 15% to class B and 6% each to class C and D. Analysis of F2 seeds from a cross between class A and class B genotypes showed that the two polypeptides (42.6 kd and 41.2 kd) are coded by nonallelic genes and also revealed that class C and class D patterns arose as a result of hybridisation between class A and class B. A. monticola, the progenitor of A. hypogaea, showed a pattern similar to the additive pattern of class A and class B while some diploid Arachis species had the 41.2 kd polypeptide. Based on arachin polypeptide patterns the probable origin of A. hypogaea has been suggested. PMID- 24240753 TI - Estimates of heritability and correlations of morphometric traits in Clarkia (Onagraceae). AB - Interspecific heritability values were estimated using parent-offspring regression analyses for 11 morphological traits differentiating Clarkia nitens and C. speciosa subsp. polyantha. Estimates ranged from near 0 for anther color and germination percentage, to 0.8 for calyx length and petal tip color. Phenotypic, genetic, and environmental correlation matrices were computed to determine the extent of interspecific correlations of traits. Cluster analyses of the genetic and environmental correlation matrices each resulted in three clusters of correlated traits; however, the clusters derived from the two matrices were different. The clusters produced by analysis of the environmental correlation matrix were similar to the factors obtained from principal component analysis of the phenotypic correlation matrix. Genetic correlations may result from strong linkage due to interspecific chromosomal differences. PMID- 24240754 TI - Transcriptional and post-transcriptional regulation of chloroplast gene expression in Petunia hybrida. AB - To study the control of differential gene expression during plastid biogenesis in Petunia hybrida, we have investigated the in vivo translation and transcription of the rbc L gene, coding for the large subunit of ribulose bisphosphate carboxylase (LSU), and the psa A gene, coding for P700 chlorophyll-a apoprotein (AP700). Differential expression of these plastid-encoded genes was studied in two developmentally different plastid systems, proplastid-like organelles from the green cell suspension AK2401 and mature chloroplasts from green leaves. In vivo translation of rbc L and psa A transcripts was analysed using specific antibodies. Specific transcript levels were analysed using internal fragments of the rbc L and psa A genes. A standardization procedure was used so that a direct correlation could be made between the amount of products and gene copy number. In Petunia hybrida the amount of LSU polypeptides present in both plastid types does not correspond to the amount of specific mRNA for the gene. Although the rbc L transcripts are present in both plastid types, the LSU protein is only present in green leaf plastids and not in cell culture plastids. In vitro translation of isolated rbc L transcripts give similar results, thereby suggesting that differences in the primary structure of the transcripts are responsible for the observed discrepancy. In contrast to this, the amount of AP700 polypeptides does correspond to the amount of the psa A transcripts. Therefore, our results indicate that the expression of chloroplast genes during plastid biogenesis takes place on at least two different levels: expression of the rbc L gene is regulated post-transcriptionally while expression of the psa A gene is regulated at the transcriptional level. PMID- 24240755 TI - Linkage disequilibrium and gametophytic self-incompatibility. AB - The approach to linkage equilibrium of a locus linked to the locus determining gametophytic self-incompatibility (S) is considered. For the simplest case of three alleles at the S locus and two at the linked locus it is necessary to consider 3 measures of linkage disequilibrium. These are found to approach their equilibrium value of zero in one of three ways: 1) steadily declining to zero; 2) oscillating as decline proceeds; 3) a combination: 2) followed by 1). Linkage equilibrium may be established before genotype frequencies reach their expectation under random crossing. Earlier studies (Li 1951; Moran 1962) of the approach to S allele equilibrium have been based on the assumption that all types of pollen take part in fertilizations equally frequently. Such an assumption leads to simpler expressions for changes in S gene frequencies but is extremely unrealistic and, in particular, leads to a different rate of approach to equilibrium from the more comprehensive model. It is shown that even in the absence of selection it is not possible to predict the equilibrium gene frequency of a linked locus until S allele equilibrium is reached. This frequency may be either higher or lower than that calculated from a gene count in the starting genotype pool. However, these two gene frequencies may stabilize long before linkage equilibrium is achieved. An examination of selection against one genotype at the linked locus is undertaken. If linkage is complete, lethality can be less effective at reducing the gene frequency than is less intense selection (in only a few generations of selection). Here too linkage equilibrium may be established with selection still effective in bringing about a decline in gene frequency. An examination of the analysis and conclusions of Rasmuson (1980) shows that because these were based on the inadequate formulae previously discussed and exclude phenomena discussed above, they are misleading. The possibility of a gametophytic self-incompatibility system providing a sufficient condition for the sheltering of lethals in the absence of the condition of complete linkage to the S locus (r=0) is shown to be unlikely. PMID- 24240756 TI - Some genetic consequences of skewed fecundity distributions in plants. AB - Most plant populations show a "skewedrd distribution of fecundity amongst their members, in contrast to the poisson distribution assumed by most population genetical theory. We examine by simulation the consequences of skewed fecundity for plant evolution when combined with sieve selection. In comparison with poisson-based theory, plant populations are likely to show a faster response to selection, especially when the favoured allele is at a low frequency. Selection against a deleterious immigrant allele will also be more effective, reducing its equilibrium frequency in a population. In the special case of heterozygote disadvantage traits will evolve that could not under poisson theory. However, random variation is also higher, giving a 10-plant population an effective population size of about 6.4 under poisson theory. The conclusions are not qualitatively changed by different assumptions on the exact shape of the fecundity distribution, or on heritability, or on reproduction by the smallest plants of the population. PMID- 24240757 TI - Meiotic pairing and alpha-amylase phenotype in a 5B/5R(m) Triticum aestivum - Secale montanum translocation line in common wheat. AB - A 5BS/5R(m)S translocation chromosome spontaneously recovered from a 'Chinese Spring' - Secale montanum wheat-rye telocentric 5R(m)S addition line has been identified and cytologically studied using C-banding in somatic and meiotic cells. Analysis of the translocated chromosome showed that a terminal segment of the short arm of 5B had been replaced by a short terminal region of chromosome arm 5R(m)S. The translocation led to the deletion of the genetic system promoting pairing located in 5BS, which is slightly compensated for when doses of 5R(m)S are increased, indicating homoeology to wheat chromosome 5BS. The alpha-amylase phenotype in 5B/5R(m) translocated material was studied and found to be identical to that of ditelocentric line 5BL of 'Chinese Spring'. An effect on the alpha amylase activity was detected as a result of the removal of the terminal region of 5BS, perhaps as a consequence of variation in dormancy period duration. PMID- 24240758 TI - Different AT-rich satellite DNAs in Cucurbita pepo and Cucurbita maxima. AB - The AT-rich highly repeated satellite DNA of Cucurbita pepo (zucchini) and Cucurbita maxima (pumpkin) were cloned and their DNA structure was investigated. DNA sequencing revealed that the repeat length of satellite DNA in Cucurbita pepo is 349-352 base pairs. The percentage of AT-base pairs is about 61%. This satellite is highly conserved in restriction enzyme pattern and DNA sequence; sequence heterogeneity is about 10%. In contrast, the satellite DNA of Cucurbita maxima has a repeat length of 168-169 base pairs. This satellite is also rich in AT-base pairs (64%), existing in at least three different variants as revealed by restriction enzyme analysis and DNA sequencing. The sequence heterogeneity between these variants is about 15%. The two satellite DNAs showed no cross hybridization to each other and sequence homology is only limited. Nevertheless, we found in the C. pepo genome a high amount of sequences resembling the satellite of C. maxima. In contrast, the satellite repeat of C. pepo is found in the C. maxima DNA only in a few copies. These observations were discussed with respect to satellite DNA evolution and compared to the data received from monocotyledonous species. PMID- 24240759 TI - Extent of heterosis in rice (Oryza sativa L.) under cold stress conditions - yield and its components. AB - The nature and extent of heterosis for grain yield and its component characters was estimated in a seven-parent F1-diallel cross in rice under the cold stress conditions of Palampur, representing sub-temperate climate of the mid hills of Himachal Pradesh. The highest heterotic effects for grain yield were observed in 'Himalaya 1'/'Phul Patas 72' and 'China 988'/'Himdhan' hybrids, which gave 60.36 and 32.48% heterosis, respectively, over mid parent, 38.76 and 26.86% heterosis, respectively, over high parent and 32.30 and 26.86% heterosis, respectively, over the best variety, 'Himdhan'. Heterosis for grain yield in these crosses was due to an increase in tiller number, panicle length, spikelets/panicle and 1,000 grain weight. Large number of crosses exhibited significant heterosis for high spikelet sterility and the majority of them had significant heterosis for late flowering, taking more than 120 days to flower, which resulted in lack of heterosis for grain yield in such crosses due to cold stress at the reproductive stage. PMID- 24240760 TI - Chloroplast DNA differences between two species of Oenothera subsection Munzia: location in the chloroplast genome and relevance to possible interactions between nuclear and plastid genomes. AB - The chloroplast DNAs (cpDNAs) of Oenothera berteriana and Oe. odorata (subsection Munzia) were examined by restriction endonuclease analysis with Sal I, Pvu II, Kpn I, Pst I, Hind III, and Bam HI. The fragment patterns show that these cpDNAs have all 133 restriction sites in common as well as a lot of individual bands. Nevertheless the cpDNAs of the two species can be distinguished by distinct differences in size between a small number of fragments. The 42 cleavage sites produced by Sal I, Pvu II and Kpn I were mapped on the circular cpDNAs. This was achieved by an approach which combined experimental and mathematical procedures. The overall serial order of the fragments was found to be the same for both cpDNAs. The size differences of individual fragments in the Sal I, Pvu II and Kpn I patterns between Oe. berteriana and Oe. odorata cpDNA are located within five regions scattered along the plastid chromosome. Two of these regions have been localized in the larger and one in the smaller of the two single-copy parts of the cpDNA molecule. The remaining two overlap the borders between the large single-copy and each of the duplicated parts of the molecule. The positions of distinct restriction sites are altered among the two Oenothera plastome DNAs by 0.02-0.4 MDa (30-600 base pairs). These alterations probably result from insertions/deletions. PMID- 24240761 TI - Maturing patterns of organ weights in mice selected for rapid postweaning gain. AB - Correlated responses to selection for increased 3-6 week postweaning gain in male mice were estimated for seven internal organs (testes, spleen, liver, kidneys, heart, small intestine (S intest) and stomach) weighed at specific degrees of maturity in body weight (37.5, 50.0, 62.5, 75.0, 87.5 and 100%). Correlated responses in organ weights were generally large, but the magnitude and direction of response depended upon whether 1) comparisons were made at the same age, degree of maturity or body weight and 2) absolute or proportional organ weights were used. The selected line (M16) weighed more and had larger organ weights than controls (ICR) when compared at either the same degree of maturity or the same age, indicating positive genetic correlations between body weight and the respective organ weights. Positive correlated responses were found in spleen weight/body weight at all degrees of maturity and in liver and S intest weights as a proportion of body weight at some degrees of maturity. Testes, kidneys, heart and stomach weights as a proportion of body weight had negative correlated responses, though this was consistent only for kidneys across all degrees of maturity. Correlated responses in organ weights adjusted for body weight by covariance analysis were positive for spleen, S intest and stomach and negative for testes and kidneys. Based on the constrained quadratic model, degree of maturity in organ weight relative to degree of maturity in body weight responded positively for testes, kidneys and S intest and negatively for spleen and liver. Selection for increased growth caused negative correlated responses in allometric growth of testes, kidneys, S intest and stomach. PMID- 24240763 TI - The philtrum in cleft lip: review of anatomy and techniques for construction. AB - The philtrum is imperfectly formed in both unilateral and bilateral cleft lip. Surgical construction of this exquisite feature in the upper lip is challenging and often takes a back seat to construction of Cupid's bow and the nose. However, the philtrum is one of the defining features of a normal lip. The purpose of this review is to compile information on philtral anatomy and techniques for construction to guide the reader on his or her own quest to optimize cleft lip repair. In this article, we review the normal anatomy of the philtral dimple and ridges, with particular attention to pars peripheralis configuration. We also review methods for philtral construction during primary labial repair and secondary labial revision. For unilateral cleft lip, eversion of orbicularis oris muscle is necessary to build a philtral ridge. For bilateral cleft lip, emphasis is on proper design of the philtral flap and efforts to simulate a dimple and ridges. For secondary philtral correction, techniques include complete labial revision with various types of muscular re-repair and autologous philtral ridge augmentation. Objective methods are needed to document the efficacy of the many techniques for philtral construction and reconstruction. PMID- 24240764 TI - Clinical application of the FACES score for face transplantation. AB - OBJECTIVE: This study aimed to systematically evaluate all reported outcomes of facial allotransplantation (FT) using the previously described FACES scoring instrument. METHODS: This was a retrospective study of all consecutive face transplants to date (January 2012). Candidates were identified using medical and general internet database searches. Medical literature and media reports were reviewed for details regarding demographic, operative, anatomic, and psychosocial data, which were then used to formulate FACES scores. Pre-transplant and post transplant scores for "functional status", "aesthetic deformity", "co morbidities", "exposed tissue", and "surgical history" were calculated. Scores were statistically compared using paired-samples analyses. RESULTS: Twenty consecutive patients were identified, with 18 surviving recipients. The sample was composed of 3 females and 17 males, with a mean age of 35.0 +/- 11.0 years (range: 19-57 years). Overall, data reporting for functional parameters was poor. Six subjects had complete pre-transplant and post-transplant data available for all 5 FACES domains. The mean pre-transplant FACES score was 33.5 +/- 8.8 (range: 23-44); the mean post-transplant score was 21.5 +/- 5.9 (range: 14-32) and was statistically significantly lower than the pre-transplant score (P = 0.02). Among the individual domains, FT conferred a statistically significant improvement in aesthetic defect scores and exposed tissue scores (P <= 0.01) while, at the same time, it displayed no significant increases in co-morbidity (P = 0.17). CONCLUSION: There is a significant deficiency in functional outcome reports thus far. Moreover, FT resulted in improved overall FACES score, with the most dramatic improvements noted in aesthetic defect and exposed tissue scores. PMID- 24240765 TI - Discrimination among adults with craniofacial conditions. AB - The primary goal of this study was to establish the level of perceived discrimination experienced by adults with congenital craniofacial conditions in Australia and to examine predictors of discrimination. Specifically, this study tested whether social support mediates the relationship between discrimination and health. Adults (n = 93) who had been treated at the Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide for congenital craniofacial conditions (not including cleft lip and/or palate) completed questionnaires examining satisfaction with life, quality of life, anxiety and depression, self esteem, satisfaction with social support, and satisfaction with appearance. A substantial minority of adults with congenital craniofacial conditions reported that they experience discrimination almost every day in a range of areas. Higher reports of discrimination were related to older age, being male, and less education. Other factors related to higher discrimination included lower levels of satisfaction with life, self-esteem, satisfaction with appearance and mental quality of life, as well as higher levels of anxiety and depression. Social support partially mediated the relationship between discrimination and mental health outcomes. The current study shows that discrimination experiences continue into adulthood confirming the importance of ensuring patients are well supported both by psychosocial services as well as within their own social support networks. PMID- 24240766 TI - Minimizing transfusions in primary cranial vault remodeling: the role of aminocaproic acid. AB - BACKGROUND: Cranial vault remodeling (CVR) for craniosynostosis is a procedure with the potential for significant blood loss. Aminocaproic acid (ACA) has been used at our institution during CVR for its antifibrinolytic effects. The purpose of this study was to investigate the effect of ACA on blood loss and transfusion rates during primary CVR. METHODS: Three hundred eighty-three patients with craniosynostosis underwent primary CVR at a single institution by a single surgeon over 15 years. Patients were included if they received either ACA or no antifibrinolytic. The estimated blood loss (EBL) and volume of blood transfused was recorded. Thrombotic-related complications were identified. Comparisons were made between subgroups using independent Student t test and Fisher exact test. RESULTS: Among the study population, 148 patients met inclusion criteria. ACA was given to 30 patients, while 118 patients received no antifibrinolytic. There was no difference in the average intraoperative EBL between the ACA (322 mL) and control groups (327 mL, P > 0.05). Additionally, the incidence of transfusion was not significantly different between subgroups (97% vs. 86%, respectively, P > 0.05). Patients treated with ACA, however, received lower average perioperative transfusion volumes (25.5 mL/kg) compared to control patients (53.3 mL/kg, P < 0.0001). Furthermore, patients in the ACA subgroup were less likely to require a second unit of blood (21% vs. 43%, P < 0.0001) and therefore had fewer exposures to donor blood antigens (ARR = 22%, NNT = 4.6). CONCLUSIONS: The use of intraoperative ACA minimizes blood transfusion volumes and donor exposures in children who undergo primary CVR for craniosynostosis. Antifibrinolytics should be considered for routine use in pediatric craniofacial surgery. PMID- 24240767 TI - Common patterns of reconstruction for Mohs defects in the head and neck. AB - BACKGROUND: Skin cancer is the most common of all cancers. Mohs surgery is an effective technique for removing common types of skin cancer. The number of patients presenting for reconstruction after Mohs surgery has been increasing in recent years. Reconstructive surgeons are faced with diverse defects of different sizes and locations. The aim of this study was to examine reconstructive methods for Mohs defects to aid in preoperative planning. METHODS: We reviewed the charts of 245 patients who underwent Mohs defect reconstruction over a period of 5 years. The patients were categorized according to the reconstructive technique (eg, flap, full-thickness skin graft, split-thickness skin graft) used in relation to anatomic location and the size of the defect. RESULTS: One hundred twenty-nine patients (53%) had Mohs defects of the nose. Bilobed flap reconstruction was the most common for the nasal ala (17/42 [40%]), tip (19/41 [46%]), and nasal sidewall (8/25 [32%]). Forehead flap reconstruction was most common for nasal dorsum defects (9/16 [56%]). Linear closure was the most common reconstructive technique for the cheek (18/34 [53%]), the forehead (13/20 [65%]), the chin (4/4 [100%]), the lower lip (4/4 [100%]), the upper lip (8/13 [38%]), the auricle (4/10 [40%]), the eyelid (5/8 [62%]), and the temporal region (2/5 [40%]). Composite grafting was the most common in the nasal columella (2/3 [67%]) and full-thickness skin graft for nasal sill defects (2/2 [100%]). Split thickness skin graft was the most common in the scalp (3/6 [50%]). CONCLUSIONS: Various options exist for Mohs repair. Understanding trends of reconstructing Mohs defects may help in planning the best method of reconstruction. PMID- 24240768 TI - Three-dimensional analysis of foramen magnum and its adjacent structures. AB - The goal of this effort is to evaluate the anatomy of the foramen magnum (FM) using 3-dimensional computed tomography (3D CT), and determine whether or not the anatomical features of vascular structures and condylar foramen (CF) affect the types of FM.The CT angiography records of 101 patients (44 men and 57 women) were retrospectively examined in this study. Details of the FM, CF, and the vertebral and basilar arteries were examined using maximum intensity projection and 3D rendering images. The average age of the 101 patients was 45.28 +/- 16.3 years. The 8 types of FM, in order of their frequency of occurrence, are as follows: round (19 cases; 18.8%), 2 semicircles (18; 17.8%), egg-shaped (15; 14.9%), hexagonal (14; 13.9%), tetragonal (11; 10.9%), oval (11; 10.9%), pentagonal (9; 8.9%), and irregular (4; 4%). There was no statistically significant relationship between the anatomical features of the vertebral and basilar arteries and the CF with the different types of FM (P >= 0.05). In our study, the diameter of the anteroposterior (AP) FM was 34.7 +/- 3.6 mm, and the transverse (T) diameter was 29.5 +/- 2.5 mm. The AP and T diameters were significantly higher in men than in women (P = 0.006 and P <= 0.001, respectively).Our study revealed that 3D CT is a safe and easy method for visualizing the anatomical structure of the FM and neighboring structures. Furthermore, this study was the first to demonstrate that there is no correlation between the 8 types of FM and the vertebral artery, basilar artery, and CF. PMID- 24240769 TI - Repair of symptomatic nasoseptal perforations using mucosal regeneration technique with interpositional grafts. AB - Over the past 60 years, many surgical techniques have been developed for the repair of nasoseptal perforations. This study describes a safe and practical technique involving the 5-layer repair of symptomatic nasoseptal perforations without mucosal flaps. The present study involved 23 patients (17 men and 6 women) who had symptomatic nasoseptal perforations in the Otorhinolaryngology and Head Neck Surgery Department of Haseki Research and Training Hospital. Patients were treated using the mucosal regeneration technique. Follow-up examinations were performed at 3 and 6 months postoperatively. The surgery was considered successful if total closure was achieved. Nasal mucosal physiology was also assessed preoperatively and at 3 and 6 months postoperatively by measuring the nasal mucociliary clearance time by means of the saccharin test. The most common etiological factor was former nasal surgery (56.5%), followed by nasal trauma (26%). In 4 patients (17.5%), the perforations were idiopathic. The average preoperative perforation size was 1.74 +/- 0.87 cm. Total closure of the perforation was achieved in 21 patients (91.3%), and only 2 patients had subtotal healing. The mean preoperative mucociliary clearance time was 19.3 +/- 4.15 minutes, which significantly improved to 12.4 +/- 3.53 minutes and 10.1 +/- 3.21 minutes at 3 and 6 postoperative months, respectively. Mucosal regeneration technique with interpositional grafts can be used to safely and reliably repair medium-to-large nasoseptal perforations. PMID- 24240770 TI - Periodontal growth in areas of vascular malformation in patients with Sturge Weber syndrome: a management protocol. AB - Sturge-Weber syndrome (SWS) is a very rare condition characterized by abnormal vascular formations that encompass several manifestations: cutaneous, neurologic, ocular, and oral. Neurologic conditions are the most important factor, especially epilepsy, which frequently leads patients to make use of anticonvulsants. These drugs are capable of inducing abnormal tissue growth in the oral cavity that can be situated over areas with vascular malformation, requiring special attention by the clinician. This report describes 1 case of SWS and performs a literature review of treatments for this condition, providing a protocol of treatment for these clinical situations. PMID- 24240771 TI - Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy. AB - Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells, and defects in mitophagy correlate with ageing phenomena and with several neurodegenerative disorders. A central mechanistic question regarding mitophagy is whether mitochondria are consumed en masse, or whether an active process segregates defective molecules from functional ones within the mitochondrial network, thus allowing a more efficient culling mechanism. Here we combine a proteomic study with a molecular genetics and cell biology approach to determine whether such a segregation process occurs in yeast mitochondria. We find that different mitochondrial matrix proteins undergo mitophagic degradation at distinctly different rates, supporting the active segregation hypothesis. These differential degradation rates depend on mitochondrial dynamics, suggesting a mechanism coupling weak physical segregation with mitochondrial dynamics to achieve a distillation-like effect. In agreement, the rates of mitophagic degradation strongly correlate with the degree of physical segregation of specific matrix proteins. PMID- 24240772 TI - Treatment of post-mastectomy pain syndrome with acupuncture: a case report. AB - Post-mastectomy pain syndrome (PMPS) is a common and severe neuropathic pain syndrome arising after breast surgery. Since few effective allopathic treatments exist for PMPS, many patients may seek assistance from complementary and alternative medicine. Here, we report a case of a woman with severe and persistent PMPS who was successfully treated with acupuncture. PMID- 24240773 TI - Amino acid-dependent regulation of food intake: is protein more than the sum of its parts? PMID- 24240774 TI - Golgi meet Cajal: coupling and feedback at retinal photoreceptors. PMID- 24240775 TI - Neural circuits in movement control. PMID- 24240776 TI - Anaesthesia in Ethiopia: providers' perspectives on the current state of the service. AB - The improvement of surgical and anaesthetic safety in low-resource settings is hampered by a lack of reliable information on the current provision of these services. Ethiopia is one of the world's poorest countries and, despite large amounts of both foreign and domestic investment, still reports some of the worst health outcomes. However, information on anaesthesia and surgical provision is sparse. This work reproduces a questionnaire study, first used in Uganda in 2006, to survey practising anaesthetists regarding the current state of anaesthesia services across Ethiopia. The results indicate that a large proportion of centres remain unable to provide safe general, spinal, paediatric and obstetric anaesthesia, at all levels of hospital and across almost all of the country's regions. In addition to a lack of equipment and pharmaceuticals, anaesthetists report problems with professional recognition and a lack of access to continuing professional development as key barriers to service development. PMID- 24240779 TI - The effects of low-fluoride toothpaste supplemented with calcium glycerophosphate on enamel demineralization. AB - OBJECTIVES: The aim of the present study was to evaluate the effects of different concentrations of calcium glycerophosphate (CaGP) in toothpastes with low fluoride (low-F) concentrations on enamel demineralization by using a bovine enamel and pH cycling model. MATERIALS AND METHODS: Experimental toothpastes containing 0 or 500 MUg F/g (NaF) and CaGP concentrations of 0, 0.1, 0.25, 0.5, 1, and 2 % were manufactured. A commercial toothpaste was used as a positive control (1,100 MUg F/g). After polishing and hardness tests, enamel blocks were subjected to pH cycling for 5 days and toothpaste treatment twice daily. The treatment regimen involved soaking all blocks in the corresponding slurry for 1 min (2 ml/block). Surface and cross-sectional hardness and fluoride concentrations in enamel were analyzed. The hardness data were analyzed using a one-way ANOVA followed by a Bonferroni post hoc test. Fluoride concentrations were analyzed using a Kruskal-Wallis followed by a Student-Newman-Keuls post hoc test. RESULTS: The mineral loss with the toothpaste containing 500 MUg F/g and 0.25 % CaGP was lower than that in the other groups (p < 0.05). Fluoride concentrations in the enamel treated with 0.1, 0.25, and 0.5 % CaGP toothpastes were similar to those in the enamel treated with the 500 MUg F/g toothpaste (p > 0.05). A greater concentration of CaGP reduced the fluoride levels in enamel (p < 0.05). CONCLUSIONS: The results from the present in vitro study show that a low-F (500 MUg F/g) toothpaste is capable of maintaining the efficacy of 1,100 MUg F/g toothpaste when supplemented with 0.25 % of CaGP. CLINICAL RELEVANCE: The developed toothpaste prevents caries as a standard one and is safe for individuals of any age group. PMID- 24240777 TI - Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial. AB - IMPORTANCE: Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE: To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS: Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES: Primary outcome was a combination of death and major disability (modified Rankin Scale score >=3) at 14 days or hospital discharge. RESULTS: Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE: Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01840072. PMID- 24240780 TI - Gamete-type dependent crossover interference levels in a defined region of Caenorhabditis elegans chromosome V. AB - In certain organisms, numbers of crossover events for any single chromosome are limited ("crossover interference") so that double crossover events are obtained at much lower frequencies than would be expected from the simple product of independent single-crossover events. We present a number of observations during which we examined interference over a large region of Caenorhabditis elegans chromosome V. Examining this region for multiple crossover events in heteroallelic configurations with limited dimorphism, we observed high levels of crossover interference in oocytes with only partial interference in spermatocytes. PMID- 24240781 TI - Major QTLs control resistance to rice hoja blanca virus and its vector Tagosodes orizicolus. AB - Rice hoja blanca (white leaf) disease can cause severe yield losses in rice in the Americas. The disease is caused by the rice hoja blanca virus (RHBV), which is transmitted by the planthopper vector Tagosodes orizicolus. Because classical breeding schemes for this disease rely on expensive, time-consuming screenings, there is a need for alternatives such as marker-aided selection. The varieties Fedearroz 2000 and Fedearroz 50, which are resistant to RHBV and to the feeding damage caused by T. orizicolus, were crossed with the susceptible line WC366 to produce segregating F2:3 populations. The F3 families were scored for their resistance level to RHBV and T. orizicolus. The F2:3 lines of both crosses were genotyped using microsatellite markers. One major QTL on the short arm of chromosome 4 was identified for resistance to RHBV in the two populations. Two major QTL on chromosomes 5 and 7 were identified for resistance to T. orizicolus in the Fd2000 * WC366 and Fd50 * WC366 crosses, respectively. This comparative study using two distinct rice populations allowed for a better understanding of how the resistance to RHBV and its vector are controlled genetically. Simple marker-aided breeding schemes based on QTL information can be designed to improve rice germplasm to reduce losses caused by this important disease. PMID- 24240778 TI - SLC1 glutamate transporters. AB - The plasma membrane transporters for the neurotransmitter glutamate belong to the solute carrier 1 family. They are secondary active transporters, taking up glutamate into the cell against a substantial concentration gradient. The driving force for concentrative uptake is provided by the cotransport of Na(+) ions and the countertransport of one K(+) in a step independent of the glutamate translocation step. Due to eletrogenicity of transport, the transmembrane potential can also act as a driving force. Glutamate transporters are expressed in many tissues, but are of particular importance in the brain, where they contribute to the termination of excitatory neurotransmission. Glutamate transporters can also run in reverse, resulting in glutamate release from cells. Due to these important physiological functions, glutamate transporter expression and, therefore, the transport rate, are tightly regulated. This review summarizes recent literature on the functional and biophysical properties, structure function relationships, regulation, physiological significance, and pharmacology of glutamate transporters. Particular emphasis is on the insight from rapid kinetic and electrophysiological studies, transcriptional regulation of transporter expression, and reverse transport and its importance for pathophysiological glutamate release under ischemic conditions. PMID- 24240782 TI - Comparison of area-length method by echocardiography versus full-volume quantification by cardiac magnetic resonance imaging for the assessment of left atrial volumes in children, adolescents, and young adults. AB - Left atrial (LA) size is a known predictor of adverse cardiovascular events. Echocardiography is the modality of choice for the evaluation of atrial size; however, cardiac magnetic resonance imaging (cMRI) remains the "gold standard." We sought to calculate atrial volumes using the area-length method by both echocardiography and cMRI and compare them with area-volume quantification by cMRI. Thiry-eight patients (mean age 20 +/- 12 years, 71% male) who underwent cMRI and echocardiography between September 2010 and June 2012 were retrospectively identified. The time interval between the two studies was <= 6 months. LA volumes by echocardiogram were estimated using the area-length method: LA volume = (0.85 * area(4ch) * area(2ch))/(shortest atrial length). The atrial length and area were measured in standard apical two-chamber and four-chamber planes. Measured values were indexed to body surface area (BSA). CMRI measurements were obtained from prospectively gated steady-state free precession cine stack images obtained in a standard four-chamber plane. LA volumes were calculated using Simpson's method: LA volume = LA area * (slice thickness + gap) per slice. Slice thickness ranged from 5 to 7 mm with contiguous slices of 5 to 7 mm. The values were indexed to BSA. Statistics were summarized using measures of central tendency. LA volumes by echocardiography were significantly less than those by full-volume cMRI quantification. The mean LA volume by echocardiography and full-volume cMRI were 35 +/- 14.5 and 42.4 +/- 17.2, respectively (p = 0.05). The mean difference between LA volumes obtained by the two methods was 7.4 +/- 10.6. LA volume measured by cMRI using the area-length method closely approximated full-volume assessment by cMRI with mean values of 42.9 +/- 17.4 versus 42.4 +/- 17.2, respectively (p = 0.91). There were no significant differences in the patient characteristics between the two study modalities. LA volumes as measured by echocardiography using the area-length method consistently underestimated the true volume when compared with cMRI. LA volumes measured using the area-length method by cMRI is an alternative technique for accurately quantifying chamber size and can be useful in decreasing scan time or when full volume data sets are incomplete. PMID- 24240784 TI - Combination therapies targeting multiple pathways in idiopathic pulmonary fibrosis (IPF). PMID- 24240783 TI - Tachyarrhythmias after the Norwood procedure: relationship and effect of vasoactive agents. AB - Tachyarrhythmias are common after the Norwood stage I palliation. The effects of vasoactive medications on the development of post-operative tachyarrhythmias have not been studied. The primary objective was to identify associations between postoperative tachyarrhythmias and vasoactive medication usage after Norwood stage 1 palliation. Secondary objectives included evaluation for morbidities of tachyarrhythmias and for associations with anatomical or surgical variables. Retrospective chart review was performed on all patients who underwent the Norwood stage 1 palliation at Children's Hospital Colorado between January 2008 and June 2012. Primary outcomes were development of postoperative tachyarrhythmias and the effects of vasoactive medications. Dopamine, epinephrine, milrinone, and vasopressin duration, cumulative dose, highest dose, and dose at onset of tachyarrhythmia were identified. The effects of surgical variables and anatomy were also studied. Sixty-six patients underwent the Norwood procedure, and 33 (50 %) of these patients had postoperative tachyarrhythmias. Patients with tachyarrhythmias had longer ICU stays (p = 0.02) and hospital stays (p < 0.01), but no change in mortality (p = 1.0). Multivariate Cox regression analysis showed that the right ventricle to pulmonary artery shunt (p < 0.01), longer duration of epinephrine treatment (p = 0.02), and higher milrinone dose (p = 0.002) were associated with tachyarrhythmias. Postoperative tachyarrhythmias are common after the Norwood procedure and are associated with longer ICU and hospital stays. High doses of milrinone, longer duration of epinephrine treatment, and the right ventricle to pulmonary artery shunt were associated with for the development of tachyarrhythmias. Further studies are required to determine the effects of anatomy on post-operative tachyarrhythmias. PMID- 24240785 TI - Relationship between coronary artery disease and retinopathy in patients with type 2 diabetes mellitus. AB - OBJECTIVE: To examine risk factors for coronary artery disease (CAD) and retinopathy in patients with type 2 diabetes mellitus (DM) and assess the relationship between CAD and retinopathy. METHODS: A total of 1,003 outpatients with type 2 DM (578 men and 425 women) were classified into two groups according to the presence (based on ischemic findings on a resting electrocardiogram or a history of angina or myocardial infarction) or absence of CAD and four retinopathy stages based on the International Clinical Classification of Diabetic Retinopathy. RESULTS: Stepwise multiple regression analyses showed that independent risk factors for CAD were age, the triglyceride (TG) level and smoking, while those for retinopathy included age, age of DM diagnosis, the HbA1c level and a female gender. The prevalence of CAD increased in association with the progression of retinopathy (p<0.01). CONCLUSION: Since it is difficult to distinguish macrovascular and microvascular diseases, diabetic vascular disorders require comprehensive approaches to assessment and treatment. PMID- 24240786 TI - Clinical and pathological studies of IgA nephropathy presenting as a rapidly progressive form of glomerulonephritis. AB - OBJECTIVE: IgA nephropathy (IgAN) is widely regarded as a slowly progressive disease. However, a minor population of patients present with a rapidly progressive form of glomerulonephritis (RPGN). METHODS: We studied 25 cases of IgAN who presented with RPGN. The laboratory data, histology, and five-year prognosis after diagnostic renal biopsy were evaluated. We compared the data of these patients with those of 495 patients with the non-RPGN type. In addition, we divided the patients with the RPGN type of IgAN into a group with reduced renal function and a group with maintained renal function, and compared the data between the two groups. RESULTS: In the 'RPGN type', the serum creatinine levels and a 24-hour urinary protein excretion were significantly higher than in the non RPGN type. Histological examinations showed that the rates of endocapillary hypercellularity and tubular atrophy/interstitial fibrosis were significantly higher in the patients with the RPGN type. In the comparison between the groups with reduced and maintained renal functions, the former group exhibited higher levels of proteinuria, serum creatinine and crescent formation than the latter group. CONCLUSION: The RPGN type of IgAN was significantly worse in terms of the renal survival rate at five years than the non-RPGN type. Intensive and active treatments are necessary for this minor population, according to the guideline for the management of RPGN. PMID- 24240787 TI - Efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis. AB - OBJECTIVE: To assess the efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis (IPF), we conducted a retrospective study of patients who received pirfenidone therapy. In addition, the combined effects of inhaled N-acetylcysteine (NAC) and pirfenidone were evaluated. METHODS: Eligible patients had a clinical and radiologic diagnosis of advanced-stage IPF (stages of severity III&IV). Patients who exhibited a relative decline in forced vital capacity (FVC) of 10% or more within the preceding six (+/-2) months were enrolled. The outcome was evaluated from the date of the 6-month follow-up PFT. Relative declines in FVC of more than 10% were defined as progressive disease (ineffective group), while those less than 10% were defined as stable disease (effective group). The clinical features were compared between the two groups. We also compared the efficacy of the combined therapy with inhaled NAC and pirfenidone (n=11) with that of pirfenidone alone (n=7). RESULTS: Eighteen patients 59-82 years of age with IPF who received pirfenidone therapy were reviewed. Pirfenidone stabilized declines in FVC by 10% at six months in eight of the 18 cases (44%). The median changes in FVC at six months were +120 mL in the effective group and -590 mL in the ineffective group. The number of NAC users was significantly higher in the effective group (7/8=87.5%) than in the ineffective group (3/10=30%) (p=0.02). Furthermore, the use of combined NAC therapy was correlated with a favorable outcome. The median change in FVC at six months was 0 mL in the NAC group and -290 mL in the non-NAC group. The median survival period was 557 +/- 66 days in the NAC group and 196 +/- 57 days in the non-NAC group (p=0.03). CONCLUSION: Among the advanced-stage IPF patients with a more progressive status, pirfenidone decreased the rate of decline in FVC. In addition, patients treated with pirfenidone combined with NAC therapy exhibited favorable outcomes. Additional studies are needed to confirm the efficacy of this combined therapy for IPF. PMID- 24240788 TI - Long-term outcome and efficacy of cyclophosphamide therapy in Japanese patients with ANCA-associated microscopic polyangiitis: a retrospective study. AB - OBJECTIVE: The aim of this study was to elucidate the efficacy of cyclophosphamide (CY) in Japanese patients with antineutrophil cystoplasmic antibody (ANCA)-associated microscopic polyangiitis (MPA). METHODS: Sixty-four patients, newly diagnosed with ANCA-associated MPA were included in this retrospective study. The patients were divided into two groups based on whether they received combination therapy of CY and corticosteroid (CS) (CY group, n=29) or CS alone (CS group, n=35) for remission induction. The primary outcome was all cause mortality. RESULTS: Most patients in the CY group were treated with oral CY. Between the two groups, there were no differences in the baseline characteristics except for a higher proportion of male patients in the CY group. The remission rate was not substantially different between the two groups (86.2% in the CY group vs. 91.4% in the CS group). The survival rate was slightly higher in the CY group than in the CS group (not statistically significant; 0.86 vs. 0.77 at 1 year and 0.73 vs. 0.64 at 5 years, p=0.648). In the CY group, the hazard ratio after adjusting for age, sex, Birmingham vasculitis activity score values, serum albumin levels and C-reactive protein (CRP) levels was 0.657 (95% CI, 0.254-1.699; p=0.386). CONCLUSION: We observed no increased efficacy of CY in ANCA-positive MPA in the Japanese patients, and hence, its efficacy may be limited in these patients. PMID- 24240789 TI - Clinical analysis of patients with pulmonary nontuberculous mycobacterial disease complicated by pneumothorax. AB - OBJECTIVE: We clarified the clinical characteristics of patients with pulmonary nontuberculous mycobacterial (NTM) disease complicated by pneumothorax. METHODS: We retrospectively selected 220 patients who satisfied the diagnostic criteria for NTM disease proposed by the American Thoracic Society (ATS). Nine patients with pulmonary NTM disease were complicated with pneumothorax. We investigated the patients' background, laboratory findings, radiological findings, treatment and prognoses. RESULTS: There were nine patients, including six men and three women, with a mean age of 73.2 years. Seven patients had underlying respiratory diseases such as chronic obstructive pulmonary disease (COPD) excluding pulmonary NTM disease. The causative microorganisms was Mycobacterium avium in four patients, M. intracellulare in four patients, and M. kansasii in one patient. Regarding the radiological findings, pneumothorax was recognized in the right lung in five patients, in the left lung in three patients, and in both lungs heterogeneously in one patient. Although most patients exhibited multiple cavities and extensive lesions over the unilateral lung fields, three patients were simultaneously diagnosed with pulmonary NTM disease at the onset of pneumothorax. As for treatment, thoracic drainage was performed in seven patients, while one patient was advised only to rest and one patient required both thoracic drainage and surgery. The responses to the treatment was poor in each case, and five patients died due to pneumonia or heart failure. CONCLUSION: In this study, the rate of pneumothorax complications in the patients with pulmonary NTM disease (4.1%) was higher than that of other reports. The responses to treatment, and prognoses were poor due to the presence of other complications. PMID- 24240790 TI - Peritonitis caused by Aeromonas species at a hospital in southern Taiwan. AB - OBJECTIVE: This study was conducted to investigate the clinical characteristics of patients with Aeromonas peritonitis, particularly secondary peritonitis. METHODS: Patients with Aeromonas peritonitis treated between July 2004 and December 2011 were identified from the computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. RESULTS: A total of 50 patients with Aeromonas peritonitis were identified. Nine cases were classified as spontaneous bacterial peritonitis, and 41 cases were classified as secondary peritonitis. The most common etiology of secondary peritonitis was acute appendicitis (n=26), followed by small bowel perforation (n=7) and colon perforation (n=6). The patients with spontaneous bacterial peritonitis were more likely to be immunocompromised (p=0.0013) and more frequently had an initial presentation of shock (p=0.0129), an abnormal liver function (p<0.05) and concomitant bacteremia (p=0.0024) than the patients with secondary peritonitis. Although the patients with secondary peritonitis had higher levels of inflammatory parameters, including leukocytes and C-reactive protein, and more frequent polymicrobial infections, their survival outcome rates, such as in-hospital mortality, were significantly lower (p=0.0007). The overall in-hospital mortality rate was 20%, and initial shock was the only independent prognostic factor for mortality (p=0.012). CONCLUSION: The clinical characteristics, including outcomes, of patients with spontaneous and secondary Aeromonas peritonitis differ. In-hospital mortality is significantly associated with the initial presentation of shock. PMID- 24240791 TI - Solitary amyloidosis of the sigmoid colon featuring submucosal tumor caused hematochezia. AB - A previously a healthy 64-year-old woman complained of a two-week history of hemorrhaging upon defecation. The laboratory and urinalysis findings were normal, and no serum or urine M components were detectable on protein electrophoresis. An air contrast barium enema revealed an elevated lesion measuring -20 mm in diameter with a smooth surface and a depression in the sigmoid colon. Colonoscopy revealed a red colored and congested tumor. The exposed surface of the submucosal tumor (SMT) center was somewhat yellow in color and covered with fuzz. All other portions of the colon were normal. The endoscopy and double-contrast barium revealed a normal upper gastrointestinal tract and a normal small intestine, respectively. A histopathological evaluation of a biopsy specimen obtained from the SMT suggested amyloid deposition. However, the other biopsy specimens of the esophagus, stomach, duodenal bulb, second portion of the duodenum, terminal ileum and other portions of the colon demonstrated no amyloid deposition. Colonoscopic ultrasonography (US) revealed the hypoechoic, homogeneous SMT to be mainly localized within the submucosa. An endoscopic submucosal resection (EMR) of the solitary amyloidosis was performed and the immunohistopathology revealed the entire SMT to consist of amyloid light chain kappa amyloid deposition. We considered that the US followed by EMR contributed to the precise diagnosis of solitary amyloidosis and the treatment of hematochezia caused by a solitary area of amyloidosis within the sigmoid colon. PMID- 24240792 TI - A murmur-free giant myxoma discovered incidentally on abdominal ultrasonography. AB - Patients with myxoma normally present with cardiovascular symptoms due to mitral valve obstruction caused by the tumor. However, some cases are difficult to diagnose because the findings of auscultation are normal and there are no cardiovascular symptoms. A 62-year-old man presented at a nearby clinic with a fever. No cardiac murmurs were heard on a physical examination. Abdominal ultrasonography was conducted to evaluate the origin of the fever, and a giant left atrial myxoma was discovered incidentally. Although many myxoma cases are found on transthoracic echocardiography, we herein describe a case of a giant left atrial myxoma incidentally discovered on abdominal ultrasonography. PMID- 24240793 TI - Coronary sinus draining into the left subclavian vein through a persistent left superior vena cava. AB - A persistent left superior vena cava (PLSVC) is formed by the remains of the oblique vein of the left atrium, which is not completely degenerated during embryonic development. The incidence is approximately 0.3% in the general population. Approximately 80-92% of PLSVCs drain into the right atrium through the coronary sinus. This report describes a rare case of PLSVC in which the coronary sinus (CS) did not open into the right atrium, but rather drained into the left subclavian vein through the PLSVC. PMID- 24240794 TI - Simultaneous occurrence of type 1 diabetes mellitus and Graves' disease: a report of two cases and a review of the literature. AB - Two unrelated Japanese women, 41 and 27 years of age, were admitted with histories of thirst, weight loss and palpitations of a few weeks' duration. Both were diagnosed to have diabetic ketosis or ketoacidosis with acute-onset type 1 diabetes (T1D) and Graves' disease (GD) (autoimmune polyglandular syndrome type 3 variant; APS3v), and were treated with intensive insulin therapy and anti-thyroid drugs. Human leukocyte antigen examinations showed that both cases had the HLA A2, A24, B54, and DRB1*04:05-DQA1*03:03-DQB1*04:01 haplotype, which made them susceptible not only to APS3v, but also to both acute-onset T1D and GD. The genetic background of patients strongly contributes to the simultaneous occurrence of T1D and GD. PMID- 24240795 TI - IgG4-related ocular adnexal disease mimicking thyroid-associated orbitopathy. AB - A 72-year-old man presented with bilateral eyelid swelling and redness. An orbital CT scan showed bilateral proptosis, extraocular muscle enlargement and swollen lacrimal glands, mimicking thyroid-associated orbitopathy (TAO) with Hashimoto's thyroiditis (HT). During the patient's clinical course, spontaneous remission of lung consolidation (35 * 26 mm) was seen. A diagnosis of IgG4 related disease (IgG4-RD) was made based on an elevated serum IgG4 level (1,020 mg/dL; normal, 4-108), predominance of IgG4-positive plasma cells (IgG4/IgG: 35/70 in HPF) in the lacrimal glands and typical features of Mikulicz's disease. This report provides a novel description of this unusual disease entity among HT, TAO and IgG4-RD. PMID- 24240796 TI - EBUS-TBNA-related complications in a patient with tuberculous lymphadenopathy. AB - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming more common for diagnosing intrathoracic lymphadenopathy, including tuberculous lymphadenopathy. We herein report two cases of complications possibly related to EBUS-TBNA for tuberculous lymphadenopathy. The first patient was a 26 year-old woman who developed intrabronchial polypoid granulomas exclusively at puncture sites two months after undergoing EBUS-TBNA. Although endobronchial extension may occur, the risk of aggravation caused by puncture should be considered. The second patient was a 39-year-old woman with transient smear positive bloody sputum that developed immediately after EBUS-TBNA and persisted for three days. Temporary isolation following EBUS-TBNA should be considered for possible tuberculous lymphadenopathy. PMID- 24240797 TI - Lymphomatosis cerebri with intramedullary spinal cord involvement. AB - Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma (PCNSL). Little is known about cases of LC with spinal cord involvement. Among the 11 PCNSL patients treated in our hospital during a four-year period, we identified two cases of LC with spinal cord lesions. One showed a spinal cord lesion followed by leukoencephalopathy. The other showed a spinal cord lesion after LC. In both cases, the histopathology was diffuse large B-cell lymphoma. It is possible that LC may affect the entire central nerve system, and tumor infiltration to the brain and spinal cord in LC may occur more frequently than has been previously considered. PMID- 24240798 TI - Dasatinib-responsive chronic lymphocytic leukemia in a patient treated for coexisting chronic myeloid leukemia. AB - We herein present a case of concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Two different clones, a Philadelphia (Ph) clone and a CLL clone with a 13q deletion, were identified using fluorescent in situ hybridization. Dasatinib was administered to inhibit Bcr-Abl and Lyn kinase. The patient exhibited a molecular response for CML and a partial response for CLL. To our knowledge, this is the first report to describe the occurrence of a gradual increase in the Bcr-Abl transcript level prior to the diagnosis of Ph-positive CML in an individual with CLL who was successfully treated with dasatinib as the first-line therapy. PMID- 24240799 TI - Acute myelogenous leukemia with Leptotrichia trevisanii bacteremia. AB - A 74-year-old woman visited an otolaryngology clinic with pharyngeal pain, and was diagnosed with a peritonsillar abscess. She received antibiotics and underwent incisional drainage, but displayed high white blood cell and blast cell counts, and was referred to our hospital. Gram-negative rods (Leptotrichia trevisanii) were detected in blood cultures performed on admission. She was diagnosed with bacteremia and acute myelogenous leukemia (FAB classification: M1). After antibiotic therapy, she temporarily recovered from the bacteremia, but subsequently died on day 34. Although Leptotrichia trevisanii bacteremia is extremely rare, clinicians should consider it in cases involving immunocompromised patients with oral lesions. PMID- 24240800 TI - Ineffectiveness of daptomycin in the treatment of septic pulmonary emboli and persistent bacteremia caused by methicillin-resistant Staphylococcus aureus. AB - A 73-year-old man with long-term food deprivation and total parenteral nutrition was diagnosed with septic pulmonary emboli (SPE) and a persistent bacteremia caused by central line-associated blood stream methicillin-resistant Staphylococcus aureus (MRSA) infection. Although daptomycin (DAP) failed to treat the persistent bacteremia, linezolid successfully controlled it. DAP is inactivated by lung surfactant, and therefore, it should not be administered for lower respiratory infections. However, SPE caused by MRSA has been reported to be treatable with DAP since it is an infection of the lung parenchyma. We herein report the lack of effect of daptomycin in SPE treatment. PMID- 24240801 TI - Miliary tuberculosis with indeterminate interferon gamma release assay results. AB - Recently, interferon gamma release assays (IGRAs) have become an important clinical tool for detecting latent tuberculosis. However, IGRA results may impede making a diagnosis. We herein present an interesting case of miliary tuberculosis with a nonspecific IGRA reaction due to hemophagocytosis. PMID- 24240802 TI - Fitz-Hugh-Curtis syndrome-like findings: chemical stimulation by the contrast agent. PMID- 24240803 TI - Pancreatitis due to afferent loop obstruction. PMID- 24240804 TI - Left atrial metastasis of renal cell carcinoma. PMID- 24240806 TI - Fluorescence intrinsic characterization of excitation-emission matrix using multi dimensional ensemble empirical mode decomposition. AB - Excitation-emission matrix (EEM) fluorescence spectroscopy is a noninvasive method for tissue diagnosis and has become important in clinical use. However, the intrinsic characterization of EEM fluorescence remains unclear. Photobleaching and the complexity of the chemical compounds make it difficult to distinguish individual compounds due to overlapping features. Conventional studies use principal component analysis (PCA) for EEM fluorescence analysis, and the relationship between the EEM features extracted by PCA and diseases has been examined. The spectral features of different tissue constituents are not fully separable or clearly defined. Recently, a non-stationary method called multi dimensional ensemble empirical mode decomposition (MEEMD) was introduced; this method can extract the intrinsic oscillations on multiple spatial scales without loss of information. The aim of this study was to propose a fluorescence spectroscopy system for EEM measurements and to describe a method for extracting the intrinsic characteristics of EEM by MEEMD. The results indicate that, although PCA provides the principal factor for the spectral features associated with chemical compounds, MEEMD can provide additional intrinsic features with more reliable mapping of the chemical compounds. MEEMD has the potential to extract intrinsic fluorescence features and improve the detection of biochemical changes. PMID- 24240807 TI - Evaluation of the comet assay for assessing the dose-response relationship of DNA damage induced by ionizing radiation. AB - Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by gamma-ray irradiation. A clear dose response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined. PMID- 24240808 TI - Cloning, characterization and effect of TmPGRP-LE gene silencing on survival of Tenebrio molitor against Listeria monocytogenes infection. AB - Peptidoglycan recognition proteins (PGRPs) are a family of innate immune molecules that recognize bacterial peptidoglycan. PGRP-LE, a member of the PGRP family, selectively binds to diaminopimelic acid (DAP)-type peptidoglycan to activate both the immune deficiency (Imd) and proPhenoloxidase (proPO) pathways in insects. A PGRP-LE-dependent induction of autophagy to control Listeria monocytogenes has also been reported. We identified and partially characterized a novel PGRP-LE homologue, from Tenebrio molitor and analyzed its functional role in the survival of the insect against infection by a DAP-type PGN containing intracellular pathogen, L. monocytogenes. The cDNA is comprised of an open reading frame (ORF) of 990 bp and encodes a polypeptide of 329 residues. TmPGRP LE contains one PGRP domain, but lacks critical residues for amidase activity. Quantitative RT-PCR analysis showed a broad constitutive expression of the transcript at various stages of development spanning from larva to adult. RNAi mediated knockdown of the transcripts, followed by a challenge with L. monocytogenes, showed a significant reduction in survival rate of the larvae, suggesting a putative role of TmPGRP-LE in sensing and control of L. monocytogenes infection in T. molitor. These results implicate PGRP-LE as a defense protein necessary for survival of T. molitor against infection by L. monocytogenes. PMID- 24240809 TI - Synthetic resveratrol analogue, 3,3',4,4',5,5'-hexahydroxy-trans-stilbene, accelerates senescence in peritoneal mesothelium and promotes senescence dependent growth of gastrointestinal cancers. AB - 3,3',4,4',5,5'-Hexahydroxy-trans-stilbene (M8) is a synthetic resveratrol derivative, advertised as a candidate drug highly effective against numerous malignancies. Because multiple tumors prone to M8 frequently metastasize into the peritoneal cavity, this study was aimed at establishing the effect of M8 on the growth and senescence of human peritoneal mesothelial cells (HPMCs), the largest cell population within the peritoneum, actively involved in the intraperitoneal spread of cancer. The study showed that M8, used at the highest non-toxic dose of 10 MUM, impairs proliferation and accelerates senescence in cultured HPMCs via an oxidative stress-dependent mechanism. At the same time, soluble factors released to the environment by HPMCs that senesced prematurely in response to M8 promoted growth of colorectal and pancreatic carcinomas in vitro. These findings indicate that M8 may indirectly-through the modification of normal (mesothelial) cells phenotype-facilitate an expansion of cancer cells, which challenges the postulated value of this stilbene in chemotherapy. PMID- 24240810 TI - A review of microsatellite markers and their applications in rice breeding programs to improve blast disease resistance. AB - Over the last few decades, the use of molecular markers has played an increasing role in rice breeding and genetics. Of the different types of molecular markers, microsatellites have been utilized most extensively, because they can be readily amplified by PCR and the large amount of allelic variation at each locus. Microsatellites are also known as simple sequence repeats (SSR), and they are typically composed of 1-6 nucleotide repeats. These markers are abundant, distributed throughout the genome and are highly polymorphic compared with other genetic markers, as well as being species-specific and co-dominant. For these reasons, they have become increasingly important genetic markers in rice breeding programs. The evolution of new biotypes of pests and diseases as well as the pressures of climate change pose serious challenges to rice breeders, who would like to increase rice production by introducing resistance to multiple biotic and abiotic stresses. Recent advances in rice genomics have now made it possible to identify and map a number of genes through linkage to existing DNA markers. Among the more noteworthy examples of genes that have been tightly linked to molecular markers in rice are those that confer resistance or tolerance to blast. Therefore, in combination with conventional breeding approaches, marker-assisted selection (MAS) can be used to monitor the presence or lack of these genes in breeding populations. For example, marker-assisted backcross breeding has been used to integrate important genes with significant biological effects into a number of commonly grown rice varieties. The use of cost-effective, finely mapped microsatellite markers and MAS strategies should provide opportunities for breeders to develop high-yield, blast resistance rice cultivars. The aim of this review is to summarize the current knowledge concerning the linkage of microsatellite markers to rice blast resistance genes, as well as to explore the use of MAS in rice breeding programs aimed at improving blast resistance in this species. We also discuss the various advantages, disadvantages and uses of microsatellite markers relative to other molecular marker types. PMID- 24240811 TI - Size-dependent cytotoxicity of nanocarbon blacks. AB - In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and (99m)Tc radionuclide labeling techniques were used to investigate the cellular uptake of NCBs with different sizes qualitatively and quantitatively, respectively. Results showed that the cellular uptake amounts of NCBs increased with their increasing size. Large quantities of internal NCBs induced oxidative stress and nuclear damage in cells; these effects may be the critical factors involved in the cytotoxicity of NCBs. The implications associated with these findings are discussed. PMID- 24240812 TI - Synthesis of 2-acyloxycyclohexylsulfonamides and evaluation on their fungicidal activity. AB - Eighteen N-substituted phenyl-2-acyloxycyclohexylsulfonamides (III) were designed and synthesized by the reaction of N-substituted phenyl-2-hydroxyl- cycloalkylsulfonamides (I, R(1)) with acyl chloride (II, R(2)) in dichloromethane under the catalysis of TMEDA and molecular sieve. High fungicidal active compound N-(2,4,5-trichlorophenyl)-2-(2-ethoxyacetoxy) cyclohexylsulfonamide (III-18) was screened out. Mycelia growth assay against the Botrytis cinerea exhibited that EC50 and EC80 of compound III-18 were 4.17 and 17.15 MUg mL(-1) respectively, which was better than the commercial fungicide procymidone (EC50 = 4.46 MUg mL( 1) and EC80 = 35.02 MUg mL(-1)). For in vivo activity against B. cinerea in living leaf of cucumber, the control effect of compound III-18 was better than the fungicide cyprodinil. In addition, this new compound had broader fungicidal spectra than chlorothalonil. PMID- 24240814 TI - Accumulation of alpha-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease. AB - Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for alpha-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of alpha-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, alpha-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of alpha synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that alpha-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated alpha-synuclein. Accumulation of alpha-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments. PMID- 24240813 TI - Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma. AB - Better understanding of ependymoma (EPN) biology at relapse is needed to improve therapy at this critical event. Convincing data exist defining transcriptionally distinct posterior fossa (PF) sub-groups A and B at diagnosis. The clinical and biological consequence of these sub-groups at recurrence has not yet been defined. Genome and transcriptome microarray profiles and clinical variables of matched primary and first recurrent PF EPN pairs were used to identify biologically distinct patterns of progression between EPN sub-groups at recurrence. Key findings were validated by histology and immune function assays. Transcriptomic profiles were partially conserved at recurrence. However, 4 of 14 paired samples changed sub-groups at recurrence, and significant sub-group specific transcriptomic changes between primary and recurrent tumors were identified, which were predominantly immune-related. Further examination revealed that Group A primary tumors harbor an immune gene signature and cellular functionality consistent with an immunosuppressive phenotype associated with tissue remodeling and wound healing. Conversely, Group B tumors develop an adaptive, antigen-specific immune response signature and increased T-cell infiltration at recurrence. Clinical distinctions between sub-groups become more apparent after first recurrence. Group A tumors were more often sub-totally resected and had a significantly shorter time to subsequent progression and worse overall survival. Minimal tumor-specific genomic changes were observed for either PF Groups A or B at recurrence. Molecular sub-groups of PF EPN convey distinct immunobiologic signatures at diagnosis and recurrence, providing potential biologic rationale to their disparate clinical outcomes. Immunotherapeutic approaches may be warranted, particularly in Group A PF EPN. PMID- 24240815 TI - Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies. AB - Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1(125-133), LMP2A(426-434) or EBNA1(562-570) in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1(562-570) in association with HLA-A0201 was consistently observed in cell lines and EBV associated tumor biopsies. These data highlight the discordance between MHC epitope density and frequencies of associated CTL with implications for cell based immunotherapies and/or vaccines for EBV-associated disease. PMID- 24240816 TI - CT analysis of C2 pedicles morphology and considerations of useful parameters for screwing. AB - INTRODUCTION: Surgery of cervical spine steadily requires realizing posterior osteosynthesis. The anchoring of instrumentation in C2 steadily constitutes an important stake of prognosis. Pedicle screwing is one of the best options and remains associated with a low morbidity. The aim of this CT study is to provide, from a wide population, the descriptive anatomical parameters of C2 pedicles. The data enable this analysis of feasibility of C2 pedicles screwing. MATERIALS AND METHODS: A continuous and retrospective series have explored 100 CT scans of the cervical spine without finding C2 fracture. The software OSIRIX v5.0.2 has been used. The dimensions of the pedicles in C2 as length, diameter, and distance from the vertebral foramens have been measured from the preset posterior entry point. Their orientation has been described in the axial and sagittal plan by the pedicle transverse angle, the sagittal angle and the pedicle-lamina angle used as a visible mark during the procedure. At least, the feasibility of pedicle screwing has been evaluated using a diameter criterion higher than 4 mm. RESULTS: The dimensions analysis of 200 studied pedicles has found an average length as 26.18 mm, an average diameter as 5.18 mm and an average distance between the entry point and the vertebral foramen as 9.06 mm. Their orientations have an average PTA as 36.6 degrees and a SA as 25.8 degrees . The average of the PLA was 81.3. The screwing feasibility has been evaluated as 92.5 % in the whole series. CONCLUSION: These morphological data come from a large series give some help for the C2 pedicle screwing preoperative planning. These lean on 3D measures but also on accessible mark during the procedure and despite the difference of the patient orientation. A CT preoperative planning of the pedicle screwing remains essential because more than 7 % of the pedicles have a diameter lower than 4 mm. PMID- 24240817 TI - A case of atlas assimilation: description of bony and soft structures. AB - A case of atlas assimilation revealed during serial study of suboccipital region is presented. The specimen was harvested from the body of 31-year-old woman. Images of the computed tomography scans are correlated with classic dissection. Asymmetrical bony assimilation is accompanied by asymmetrical development of the suboccipital musculature. In the presented case, the atlantic segments of both vertebral arteries preserved their usual course between bony elements derived from the atlas and proatlas. Development of the soft tissues must be influenced by similar factors as development of the skeleton. Detailed radiologic studies, possibly with volumetric reconstructions, are necessary in cases of atlas assimilation before surgical interventions in the region of craniovertebral junction. PMID- 24240818 TI - Evolving practices in critical care and their influence on acute kidney injury. AB - PURPOSE OF REVIEW: This review highlights the principal advances in critical care over the past year, and discusses the impact of these advances on the diagnosis and management of acute kidney injury (AKI). RECENT FINDINGS: Recent literature has focused on assessment of volume status and fluid management, particularly in the setting of respiratory and cardiac failure. Other critical care topics are reviewed using a system-based approach. SUMMARY: The incidence of AKI appears to be increasing, and despite advances in the provision of critical care and renal replacement therapies, there has been little improvement in its associated morbidity and mortality. Nonetheless, recent advances in critical care will impact the diagnosis and management of AKI, as well as shape the future research agenda. Continued work in the fields of critical care and nephrology will undoubtedly be centered on improved biomarkers for the detection of AKI, specific therapies to mitigate or reverse AKI, and techniques to prevent the development of AKI in the critically ill population. PMID- 24240819 TI - Intravenous fluids in sepsis: what to use and what to avoid. AB - PURPOSE OF REVIEW: Septic shock is one of the most common and life-threatening conditions afflicting critically ill patients. Intravenous volume resuscitation is considered an initial and very important step in management. The most suitable fluid for volume expansion during septic shock remains unclear. In this review, we focus on the benefits and adverse effects of the most commonly used intravenous fluids in critically ill septic patients. RECENT FINDINGS: The debate about the benefits of colloids over crystalloids has been ongoing for the last few decades. With recent literature showing apparent harm from the use of hydroxyethyl starches (HESs), and given the growing concerns of adverse renal and acid-base abnormalities associated with 0.9% saline compared with balanced crystalloid solutions, it may be time to change the nature of the 'fluid debate'. SUMMARY: Crystalloids should still be considered as the first-choice drug for volume resuscitation in patients with septic shock. Colloids such as albumin can be considered in some clinical settings. HES should be avoided. Balanced crystalloids might have an important role to play in the management of septic shock. PMID- 24240820 TI - Implementing the Kidney Disease: Improving Global Outcomes/acute kidney injury guidelines in ICU patients. AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) is a frequent finding in critically ill patients and is associated with adverse outcomes. With the purpose of improving outcome of AKI, the Kidney Disease: Improving Global Outcomes (KDIGO) group, a group of experts in critical care nephrology, has presented a set of guidelines in 2012, based on the evidence gathered until mid 2011. This review will update these guidelines with recent evidence. RECENT FINDINGS: Early application of a set of therapeutic measures - a bundle - is advised for the prevention and therapy of AKI. Hemodynamic optimization remains the cornerstone of prevention and treatment of AKI. Fluid resuscitation should be with isotonic crystalloids. Recent evidence demonstrated a higher risk for renal replacement therapy (RRT) and mortality in hydroxyethyl starch-exposed patients. Further, blood pressure should be maintained by the use of vasopressors in vasomotor shock. Nephrotoxic drugs should be avoided or stopped when possible. Contrast associated AKI should be prevented by prehydration with either NaCl 0.9% or a bicarbonate solution. Other therapies, including intravenous N-acetylcysteine and hemofiltration are not recommended. Optimal timing of RRT remains controversial. Fluid overload remains an important determinant for the initiation of RRT. Continuous therapies are preferred in hemodynamically unstable patients; otherwise, choice of modality does not impact on outcomes. SUMMARY: The KDIGO guidelines as presented in 2012 provide guidelines on the domain of definition of AKI, prevention and treatment, contrast-induced AKI and dialysis interventions for AKI. Especially, early application of a set of measures, the AKI bundle, may prevent AKI and improve outcome. PMID- 24240821 TI - Measuring renal function in critically ill patients: tools and strategies for assessing glomerular filtration rate. AB - PURPOSE OF REVIEW: Alterations in kidney function are common in critically ill patients and are generally assessed by changes in serum creatinine (sCr) or urine output, which are considered surrogates for glomerular filtration rate (GFR) but do not reflect the overall kidney function. There is a great need for more reliable measurements of glomerular filtration in order to guide diagnosis and therapy for acute kidney injury. In this review, we will focus on recent advances to measure GFR that could help to better evaluate kidney function and improve patient care. RECENT FINDINGS: Standardized assays for sCr measurements, the use of a more precise scale with more frequent measurements, and the interpretation of the results based on patient's characteristics can increase the clinical value of sCr. New endogenous and exogenous markers will provide a more precise estimation. Imaging techniques are being developed and will probably be available in the near future. New gold standards for glomerular filtration will help in the development and improvement in the use of new biomarkers of kidney injury. PMID- 24240822 TI - Military trauma system in Afghanistan: lessons for civil systems? AB - PURPOSE OF REVIEW: This review focuses on development and maturation of the tactical evacuation and en route care capabilities of the military trauma system in Afghanistan and discusses hard-learned lessons that may have enduring relevance to civilian trauma systems. RECENT FINDINGS: Implementation of an evidence-based, data-driven performance improvement programme in the tactical evacuation and en route care elements of the military trauma system in Afghanistan has delivered measured improvements in casualty care outcomes. SUMMARY: Transfer of the lessons learned in the military trauma system operating in Afghanistan to civilian trauma systems with a comparable burden of prolonged evacuation times may be realized in improved patient outcomes in these systems. PMID- 24240823 TI - The 'procoagulopathy' of trauma: too much, too late? AB - PURPOSE OF REVIEW: Although early acute traumatic coagulopathy has received much recent attention, the procoagulopathy that often follows appears less appreciated. Thromboembolic disease following trauma is common and lethal, but very effective prophylactic strategies are available. These strategies are variably implemented because of the difficulty in quantifying the magnitude of procoagulopathy in individual patients. RECENT FINDINGS: The principal mechanisms of the procoagulopathy of trauma include inflammation and disseminated intravascular coagulation, tissue factor and thrombin dysregulation, and circulating microparticles and phospholipids. Quantification of these factors may allow better risk assessment in individual patients, but as yet none of these tests is in routine practice. Viscoelastic measurement of developing clot strength identifies a procoagulant state in many trauma patients, and may be a guide to the best choice of the many options for thromboembolic prophylaxis. SUMMARY: The logical next step following from the improved pathophysiological understanding of the procoagulopathy of trauma should be a simultaneous clinical trial of procoagulopathy diagnosis and thromboembolic prophylaxis. PMID- 24240824 TI - Utility of simultaneous interventional radiology and operative surgery in a dedicated suite for seriously injured patients. AB - PURPOSE OF REVIEW: In recent years, combined interventional radiology and operative suites have been proposed and are now becoming operational in select trauma centres. Given the infancy of this technology, this review aims to review the rationale, benefits and challenges of hybrid suites in the management of seriously injured patients. RECENT FINDINGS: No specific studies exist that investigate outcomes within hybrid trauma suites. Endovascular and interventional radiology techniques have been successfully employed in thoracic, abdominal, pelvic and extremity trauma. Although the association between delayed haemorrhage control and poorer patient outcomes is intuitive, most supporting scientific data are outdated. The hybrid suite model offers the potential to expedite haemorrhage control through synergistic operative, interventional radiology and resuscitative platforms. Maximizing the utility of these suites requires trained multidisciplinary teams, ergonomic and workplace considerations, as well as a fundamental paradigm shift of trauma care. This often translates into a more damage-control orientated philosophy. SUMMARY: Hybrid suites offer tremendous potential to expedite haemorrhage control in trauma patients. Outcome evaluations from trauma units that currently have operational hybrid suites are required to establish clearer guidelines and criteria for patient management. PMID- 24240825 TI - Salvage techniques in traumatic cardiac arrest: thoracotomy, extracorporeal life support, and therapeutic hypothermia. AB - PURPOSE OF REVIEW: Survival from traumatic cardiac arrest is associated with a very high mortality despite aggressive resuscitation including an Emergency Department thoracotomy (EDT). Novel salvage techniques are needed to improve these outcomes. RECENT FINDINGS: More aggressive out-of-hospital interventions, such as chest decompression or thoracotomy by emergency physicians or anesthesiologists, seem feasible and show some promise for improving outcomes. For trauma patients who suffer severe respiratory failure or refractory cardiac arrest, there seems to be an increasing role for the use of extracorporeal life support (ECLS), utilizing heparin-bonded systems to avoid systemic anticoagulation. The development of exposure hypothermia is associated with poor outcomes in trauma patients, but preclinical studies have consistently demonstrated that mild, therapeutic hypothermia (34 degrees C) improves survival from severe hemorrhagic shock. Sufficient data exist to justify a clinical trial. For patients who suffer a cardiac arrest refractory to EDT, induction of emergency preservation and resuscitation by rapid cooling to a tympanic membrane temperature of 10 degrees C may preserve vital organs long enough to allow surgical hemostasis, followed by resuscitation with cardiopulmonary bypass. SUMMARY: Salvage techniques, such as earlier thoracotomy, ECLS, and hypothermia, may allow survival from otherwise lethal injuries. PMID- 24240826 TI - What's new in operative trauma surgery in the last 10 years. AB - PURPOSE OF REVIEW: This article reviews the latest operative trauma surgery techniques and strategies, which have been published in the last 10 years. Many of the articles we reviewed come directly from combat surgery experience and may be also applied to the severely injured civilian trauma patient and in the context of terrorist attacks on civilian populations. RECENT FINDINGS: We reviewed the most important innovations in operative trauma surgery; the use of ultrasound and computed tomography in the preoperative evaluation of the penetrating trauma patient, the use of temporary vascular shunts, the current management of military wounds, the use of preperitoneal packing in pelvic fractures and the management of the multiple traumatic amputation patient. SUMMARY: The last 10 years of conflict has produced a wealth of experience and novel techniques in operative trauma surgery. The articles we review here are essential for the contemporary care of the severely injured trauma patient, whether they are card for in a level 1 trauma center or in a field hospital at the edge of a battlefield. PMID- 24240827 TI - Rotational thromboelastometry-guided trauma resuscitation. AB - PURPOSE OF REVIEW: Haemorrhage from major trauma is a significant cause of death worldwide. The UK Defence Medical Service (UK-DMS) has had significant experience in managing severely injured and shocked trauma casualties over the last decade. This has led to the integration of rotational thromboelastometry (ROTEM) into damage control resuscitation delivered at Camp Bastion Field Hospital in Afghanistan. This review aims to describe the rationale for its use and how its use has evolved by UK-DMS. RECENT FINDINGS: Although there is reasonable evidence showing its benefit in cardiac and liver surgery, evidence for its use in trauma is limited. More recent studies and meta-analyses have demonstrated a reduced rate of transfusion and blood loss, but no benefit on mortality. Despite this, there is a growing body of opinion supporting ROTEM use in trauma with European guidelines supporting its use where available. Recent UK-DMS experience has shown that it is a fast, reliable and robust means of identifying transfusion requirements. SUMMARY: ROTEM provides a means to rapidly assess coagulation in trauma casualties, allowing targeted use of blood products. It provides information on clot initiation strength and breakdown. However, its use in trauma has still to be fully evaluated. PMID- 24240828 TI - The intensivist as nosocomial thanatologist. PMID- 24240829 TI - To treat or not to treat: withholding treatment in the ICU. AB - PURPOSE OF REVIEW: Decisions to limit life-sustaining therapy (DLLST) in the ICU are used to uphold patients' autonomy, protect them from non-beneficial treatment and fairly distribute resources. The institution of these decisions is complex, with a variety of qualitative and quantitative data published. This review aims to summarize the main issues and review the contemporary research findings on this subject. RECENT FINDINGS: DLLST are used in a variety of clinical and non clinical situations, before and after ICU admission, and are not always part of end-of-life management. There are many dilemmas and barriers that beset their institution. Many ICU physicians feel inadequately trained to carry them out and they are frequently a source of conflict. A variety of strategies have been examined to improve their institution, including advanced directives, intensive communication strategies and family information leaflets, many of which have improved patient and family-centred outcomes. SUMMARY: There are a number of uncertainties that beset the institution of DLLST in the ICU; however, a variety of research has improved our ability to understand and implement them. This review frames some of the dilemmas and discusses some of the procedural strategies that have been used to improve outcomes. PMID- 24240830 TI - Causes and consequences of disproportionate care in intensive care medicine. AB - PURPOSE OF REVIEW: Increased use of advanced life-sustaining measures in patients with poor long-term expectations secondary to more chronic organ dysfunctions, comorbidities and/or a poor quality of life has become a worrying trend over the last decade. This can lead to futile, disproportionate or inappropriate care in the ICU. This review summarizes the causes and consequences of disproportionate care in the ICU. RECENT FINDINGS: Disproportionate care seems to be common in European and North American ICUs. The initiation and prolongation of disproportionate care can be related to hospital facilities, healthcare providers, the patient and his/her representatives and society. This can have serious consequences for patients, their relatives, physicians, nurses and society. SUMMARY: Disproportionate care is common in western ICUs. It can lead to violation of basic bioethical principles, suffering of patients and relatives and compassion fatigue and moral distress in healthcare providers. Avoiding inappropriate use of ICU resources and disproportionate care in the ICU should have high priority for ICU managers but also for every healthcare provider taking care of patients at the bedside. PMID- 24240831 TI - The ethics of hastening death during terminal weaning. AB - PURPOSE OF REVIEW: Withdrawal of life-sustaining medical treatment (LSMT) is under scrutiny as next-of-kin challenge medical decision-making in the courts and established end-of-life pathways are withdrawn in the face of public criticism. With persistent lobbying for medically assisted dying as the other side of the coin, and professional advice that doctors distance themselves from this activity, the fine line between defensible palliative care and hastening a death needs to be unambiguously defined, particularly with additional confounders such as transplantation initiatives. RECENT FINDINGS: The medical literature in this domain is dominated by ethical debate on euthanasia and medically assisted dying rather than defensibility within intensive care at the point of withdrawal of LSMT. SUMMARY: The process and, therefore, the timing of dying is open to manipulation by intensivists, families, other hospital physicians, courts of law and extraneous influences such as organ donation. Intensivists faced with these challenging processes need to consider some key principles to help them navigate the management of dying. They need to demonstrate transparency in order to engender trust, be responsive to the dynamically evolving needs of patient and family, avoid ambiguity, show consistency and predictability and, finally, they need to conform with society's expectations and professional standards to achieve defensibility for their actions. Adherence to these principles is likely to minimize conflict, maximize patient benefit, maintain public confidence and avoid professional jeopardy. PMID- 24240833 TI - Measuring quality of life of Finnish children with cerebral palsy. AB - PURPOSE: The purpose of the study was to examine the quality of life (QOL) of Finnish children with cerebral palsy (CP), both from the child's and the caregiver's point of view, and to analyze the effect of background factors on QOL. METHODS: This study is a part of a national CP research project. The study is based on validated questionnaires measuring QOL (CP QOL-Child). 128~questionnaires were sent to caregivers who had a 4 to 12 year-old child with CP. Children between 9 and 12 years were asked to fill in the child-self-report version. RESULTS: Responses were obtained from 78 guardians and 27 children, with a response rate of 61% in both cases. The overall QOL was reported to be good in Finnish children with CP. The correlation of QOL scores between the caregivers and children was good (n=25, r=0.687, p< 0.001), except in the domain of pain and the impact of disability. Parental estimates were consistently lower in all domains. Regarding the background factors, all the functional classification scales were associated inversely with QOL in both groups. CONCLUSION: Despite the good overall QOL, CP is perceived to limit participation. Pain impairs QOL, and pain symptoms should be systematically considered at every follow-up visit. PMID- 24240834 TI - Evidence from unilateral lesions of early uncompensable implementation of opposed response-biases in each hemisphere of the brain. AB - PURPOSE: The intact right hemisphere presents an omissive response-bias and the left hemisphere a commissive response-bias in adults. This research sought to determine whether these hemispherically lateralized response-biases manifest early developmental and uncompensable brain implementation. METHODS: Sixteen teenager and adult participants with focal left hemisphere lesions and fourteen with focal right hemisphere lesions (all with childhood onset: M=13 year recovery period) and 14 normal control participants were recruited. A computerized multitask high order working memory procedure was designed to generate many errors of omission and of commission. RESULTS: The expected double dissociation of response-bias distortion as a function of lesion side was significantly demonstrated on this task and was significantly frontal-lobe dependent. CONCLUSION: The hemispheres of the brain have an opposed response bias that is robustly implemented in infancy through adulthood. PMID- 24240835 TI - Serial casting versus stretching technique to treat knee flexion contracture in children with spina bifida: a comparative study. AB - BACKGROUND: Severe knee contractures that develop soon after muscle imbalance may not improve with stretching exercises and splinting. An alternative treatment is serial casting, which has been used to promote increased range of motion. PURPOSE: The purpose of this study was to compare the effectiveness of using serial casting and passive stretching approaches to treat knee flexion contracture in children with spina bifida. METHODS: In a pre/post randomized controlled study, ten participants were included in the serial casting group, while eight participants were included in the passive stretching intervention group. The degree of knee extension was measured at baseline, immediately after intervention, and at a one-year follow-up using a standard goniometer. RESULTS: Both groups showed significant improvements in the degree of flexion contracture at the post-treatment evaluation and the follow-up evaluation. The serial casting group showed significant improvements in knee flexion contracture at the post treatment evaluation, t (9)=13.4, p < 0.001, and the one-year follow-up evaluation, t (9) = 7.46, p < 0.001. The passive stretching group also showed significant improvements in knee flexion contracture at the post-treatment evaluation, t (7) =2.6, p < 0.05, and the one-year follow-up evaluation, t (7) = 3.6, p < 0.05. However, statistically significant improvements in the serial casting group compared with passive stretching group in relation to the degree of flexion contracture were found at the immediate post-treatment evaluation, F(1, 15)=246, p=0.0001, and the one-year follow-up evaluation, F (1, 15)=51.5, p=0.0001. CONCLUSION: The outcomes of this study provide the first evidence that serial casting may be a useful intervention in treating knee flexion contracture in children with spina bifida. However, further investigations into serial casting, as well as investigations into the use of serial casting with other interventions, are warranted. PMID- 24240836 TI - Risk of bladder cancer in patients with spina bifida: case reports and review of the literature. AB - PURPOSE: This article presents four cases of patients with spina bifida who developed bladder cancer while under our care and provides a literature review on the incidence, initial presentation, possible etiologies, and role for screening for bladder cancer in the neurogenic bladder population. METHODS: Case reports of four patients are presented followed by a literature review of the current available studies. RESULTS: Patients with spina bifida present with bladder cancer at an atypically young age with very advanced disease. The dire prognosis associated with bladder cancer in these patients demands that we provide better treatment, diagnosis, and prevention modalities. However, the potential morbidity, financial burden, and lack of proven benefit discourage cystoscopic screening in this patient population. Until we have more data on how to best serve spina bifida patients, this population should receive careful and regular urologic follow-up. CONCLUSION: Given the atypical young age of presentation and very advanced nature of bladder cancer in the spina bifida population, the authors strongly recommend that any new bladder changes, such as including increased urinary leakage, pain, recurrent infections, or increased gross hematuria, prompt immediate urologic referral for endoscopic evaluation and biopsy as indicated. PMID- 24240837 TI - Functional status of children with encephalitis in an inpatient rehabilitation setting: a case series. AB - INTRODUCTION: Patterns and predictors of recovery from encephalitis are poorly understood. METHODS: This study examined functional status and reviewed charts of all children who presented to a pediatric inpatient rehabilitation facility with encephalitis between 1996 and 2010. Functional status at admission and discharge from inpatient rehabilitation was evaluated using the Functional Independence Measure for Children (WeeFIM) Self-care, Mobility, Cognitive, and Total Developmental Functional Quotient scores (DFQ, % of age-appropriate function). Charts were reviewed to characterize key clinical features and findings. RESULTS: Of the 13 children identified, the mean age was 9 years (range 5-16) with 54% males. Mean WeeFIM Total DFQ at admission was 37 (range: 15-90) and at discharge was 64 (range: 16-96). Average change in WeeFIM Total DFQ from admission to discharge was 26.7 (range 0-55, p < 0.001). WeeFIM domain scores improved between admission and discharge (Self-Care: p < 0.001, Cognition: p < 0.01, Mobility: p < 0.001). Eleven children displayed significant impairments in functional skills, defined as DFQ of < or =85, at discharge. Key clinical features and findings were diverse and not related to functional outcome. CONCLUSIONS: Results suggest that significant functional improvement in children with encephalitis occurs during inpatient rehabilitation. Further research is necessary to identify predictors of outcome in children with encephalitis. PMID- 24240838 TI - Grisel's syndrome: an unusual cause of torticollis. AB - PURPOSE: The objective of this paper is to present a case series of patients with diagnosis of torticollis due to Grisel's syndrome and, in doing so, raise awareness of an unusual condition that could be fatal. A review of the literature is presented regarding diagnosis and treatment. METHODS: Case series of three patients that were 7, 10, and 12 years old with history of tonsillitis or neck surgery consulted to the service of Rehabilitation Medicine. RESULTS: Physical examination showed a fixed head or limitation of movement to neutral position and initially a normal neurological examination. Initial cervical X-rays were not diagnostic. The final diagnosis was made by CT scan or MRI. All 3 patients were treated with anti-inflammatory medications, immobilization, and/or cervical traction or surgery. CONCLUSION: Grisel's syndrome is a non-traumatic atlanto axial rotatory fixation (AARF) with or without subluxation following infection or surgery in the head or neck region. This paper presents an unusual cause of torticollis that could be fatal or cause neurological injury if not recognized and treated appropriately. PMID- 24240839 TI - Motor function outcome in postnatal insult-related cerebral palsy. AB - INTRODUCTION: The Gross Motor Function Classification System (GMFCS) was developed to establish uniform communication between healthcare providers, patients, and the patients' families. It is also used to prognosticate the outcome of motor function. Based on previous reports, prognostication of ambulation status in cerebral palsy is based on the motor development curve, which shows a plateau at a certain known age. CASE REPORT: This report illustrates the case of a boy with spastic triplegic cerebral palsy secondary to postnatal insult at early childhood. The patient was noted to have tremendous progressive improvement in his GMFCS level beyond 7 years old: from level IV at 4 years old to level II at 9 years old. CONCLUSION: Prognostication of ambulation in cerebral palsy based on the motor development curve provides a basis for physicians to predict motor function outcome and plan appropriate intervention. This case report shows that other important factors need to be considered in the clinical evaluation before rendering the prognostication of motor function outcome, including environmental factors as well as the etiology of cerebral palsy, for which special consideration should be given in cases of postnatal insult-related cerebral palsy. PMID- 24240840 TI - Invited commentary: Motor function outcome in postnatal insult-related cerebral palsy. PMID- 24240843 TI - Continuous electroencephalography in a surgical intensive care unit. AB - PURPOSE: Our aim was to investigate the prevalence, risk factors, and impact on outcome of nonconvulsive seizures (NCSz), nonconvulsive status epilepticus (NCSE), and periodic epileptiform discharges (PEDs) in surgical intensive care unit (SICU) patients with continuous electroencephalography (cEEG) monitoring. METHODS: This was a retrospective study of SICU patients who underwent cEEG monitoring for altered mental status over a 6-year period. We report the frequency of NCSz (including NCSE) and PEDs on cEEG. The primary outcome was death or severe disability at hospital discharge. Multivariable logistic regression was used to identify whether NCSz (including NCSE) and PEDs were independently associated with poor outcome (death, vegetative state or severe disability). RESULTS: Of 154 patients, the mean age was 64 +/- 14 years old, and 40% were women. The majority of patients were admitted following abdominal surgery (36%) and liver transplantation (24%). Sepsis developed in 100 (65%) patients. Sixteen percent (n = 24) had NCSz [including 5% (N = 8) with NCSE], and 29% (N = 45) had PEDs. All eight patients with NCSE were septic. Clinical seizures prior to cEEG and coma were more common among patients who developed NCSz or NCSE compared to patients without NCSz or NCSE (70 vs. 27%; p < 0.01; 75 vs. 52%; p = 0.046 and 63 vs. 34%; p = 0.09, respectively). NCSzs (including NCSE) were independently associated with poor outcome (20 vs. 3%, OR 10.4, 95% CI 1.0-53.7; p = 0.039). CONCLUSION: In this retrospective study of SICU patients with cEEG monitoring for altered mental status, NCSz and periodic discharges were frequent and NCSz were independently associated with poor outcome. NCSz were more common when clinical seizures occurred before cEEG. PMID- 24240844 TI - Contrast-enhanced ultrasonography for bedside imaging in subclinical acute kidney injury. PMID- 24240845 TI - Plant regeneration through somatic embryogenesis in callus culture of green bamboo (Bambusa oldhamii Munro). AB - Young inflorescence explants of green bamboo (Bambusa oldhamii Munro) in culture show a high capacity for plant regeneration through somatic embryogenesis. Embryogenic callus was initiated from explants maintained on Murashige and Skoog's medium supplemented with 3 mg/l 2,4-D, 2 mg/l kinetin and a high content (60 g/l) of sucrose. Prolonged culture in the embryoid induction medium or transferral of embryonic callus to auxin-free medium resulted in the continued development and eventual germination of embryoids and establishment of rooted plantlets that were successfully transferred to soil. PMID- 24240846 TI - A single dominant gene for Fusarium wilt resistance in protoplast-derived tomato plants. AB - Tomato plants resistant to the fungal pathogen, Fusarium oxysporum f. sp. lycopersici, race 2, were obtained using in vitro selection against fusaric acid, a non-specific toxin, as well as non-challenged cells. Protoplasts were isolated from cotyledonary tissue of tomato cv. 'UC-82', which is susceptible to Fusarium race 2. Protoplasts were challenged with the toxin, and the resistant calli were further subjected to the toxin. Plants regenerated from toxin-resistant calli were screened for resistance to the pathogen by using the Fusarium slurry inoculation technique. Seeds were collected from the surviving individuals, germinated and rescreened for resistance to the pathogen. Data obtained from this test showed a ratio of three resistant to one susceptible among R1 progenies. Further analysis of the R2 progenies confirmed that the fusarium-resistant plants were either homozygous or heterozygous dominant for the gene conferring the resistance. Similar results were recorded for tomato plants regenerated from cells that received no selection pressure. The nature of this single dominant gene-type of resistance is under investigation. PMID- 24240847 TI - New sources of dwarfing genes in pearl millet (Pennisetum americanum). AB - Thirteen naturally occurring dwarf lines of pearl millet [Pennisetum americanum (L.) Leeke], identified from the world collection, varied for several morphological and agronomic characters. Extreme dwarfs were characterized by a tufted growth habit which could be distinguished from the time of germination, while the other dwarf lines could be distinguished only after anthesis. The F1 hybrids between the tall and dwarf genotypes were tall, indicating that dwarfness is a recessive trait. In 10 out of the 13 crosses, the F2 segregation ratio was three tall to one dwarf (3?1) suggesting that the dwarfness is controlled by a single recessive gene, while the height differences in 3 of the dwarfs (IP 8056, IP 8210 and IP 8214) were controlled by more than one gene as they showed continuous variation for plant height in F2. When the remaining 10 single gene dwarfs were crossed to either d 1 ('Tift 238') or d 2 ('Tift 23 DB') dwarfs, only 2 crosses produced tall F2 hybrids and they segregated for height in F2 indicating that these 2 dwarfs are non-allelic to d 1 and d 2. Reciprocal crosses of these 2 dwarfs produced tall F1 hybrids and showed a dihybrid segregation of 9?3?4 in F2 indicating that the dwarfing genes of these 2 parents are non-allelic to each other. These non-allelic dwarfs were assigned the gene symbols d 3 (IP 10401), and d 4 (IP 10402). PMID- 24240848 TI - The molecular basis of genetic diversity among cytoplasms of Triticum and Aegilops : 5. Mitochondrial genome diversity among Aegilops species having identical chloroplast genomes. AB - Restriction fragment patterns of mtDNA isolated from the cytoplasm of three groups of Aegilops species (or accessions) which are known to carry the identical chloroplast genome but distinctly different cytoplasmic genomes (plasmons) have been analysed using five restriction endonucleases. Two to four different mitochondrial genomes are found in each group, between which the percent common restriction fragments amounts to 86-97%, whereas the same parameter obtained between mitochondrial genomes of the different groups ranges from 34 to 42%. Mitochondrial genome diversity is far more extensive than the chloroplast genome diversity, and the former provides a useful key for the phylogenetic relationships between cytoplasms of closely related species or even different accessions of the same species. The mitochondrial and chloroplast genome differentiation most certainly accounts for the plasmon variability known in this genus. PMID- 24240849 TI - Selection theory for selfed progenies. AB - The purpose of this article was to extend the model used to predict selection response with selfed progeny from 2 alleles per locus to a model which is general for number and frequency of alleles at loci. To accomplish this, 4 areas had to be dealt with: 1) simplification of the derivation and calculation of the condensed coefficients of identity; 2) presentation of the genetic variances expressed among and within selfed progenies as linear function of 5 population parameters; 3) presentation of selection response equations for selfed progenies as functions of these 5 population parameters; and 4) to identify a set of progeny to evaluate, such that one might be able to estimate these 5 population parameters.The five population parameters used in predicting gains were the additive genetic variance, the dominance variance, the covariance of additive and homozygous dominance deviations, the variance of the homozygous dominance deviations and a squared inbreeding depression term. PMID- 24240850 TI - Protein synthesis during cold shock in barley tissues : Comparison of two genotypes with winter and spring growth habit. AB - In barley (Hordeum vulgare L.) seedlings, a temperature step-down from 24 degrees C to 6 degrees C (cold shock) determined a reduction in the incorporation of labeled aminoacids and modified the electrophoretic pattern of total proteins. At 6 degrees C some new proteins appeared and others were intensified (cold shock-induced proteins= CSPs); meantime, few proteins disappeared or were curtailed (cold-repressed proteins=CRPs). The majority of the proteins of the seedlings were labeled at about the same rate both at 6 degrees C and 24 degrees C, whereas at 0 degrees C only the cold shock proteins and a few others were detectable. The cold shock-induced variations of the protein profile differed in roots and in seed remnants which showed only some of the CSPs detected in roots. Total protein synthesis of barley genotypes 'Onice' and 'Georgie', which have respectively a winter and spring growth habit, were similarly inhibited by a temperature drop. The two genotypes, however, showed some differences in the CSPs and CRPs pattern. Because 'Onice' and 'Georgie' have also a different thermotolerance, the hypothesis can be made that in barley specific CSPs are involved in conferring various degrees of cold resistance. PMID- 24240851 TI - Controlled introgression to wheat of genes from rye chromosome arm 1RS by induction of allosyndesis : 1. Isolation of recombinants. AB - Chromosome pairing between rye chromosome arm 1RS, present in two wheat-rye translocation stocks, and its wheat homoeologues was induced by introducing the translocations into either a ph1bph1b or a nullisomic 5B background. This rye arm carries a gene conferring resistance to wheat stem rust, but lines carrying the translocation produce a poor quality dough unsuitable for breadmaking. Storage protein markers were utilised along with stem rust reaction to screen for allosyndetic recombinants. From a 1DL-1RS translocation, three lines involving wheat-rye recombination were recovered, along with thirteen lines derived from wheat-wheat homoeologous recombination. From a 1BL-1RS translocation, an additional three allosyndetic recombinants were recovered. Nullisomy for chromosome 5B was as efficacious as the ph1b mutant for induction of allosyndesis, and the former stock is easier to manipulate due to the presence of a 5BL-encoded endosperm protein. The novel wheat-rye chromosomes present in the recombinant lines may enable the rye disease resistance to be exploited without the associated dough quality defect. PMID- 24240852 TI - Controlled introgression to wheat of genes from rye chromosome arm 1RS by induction of allosyndesis : 2. Characterisation of recombinants. AB - Sixteen allosyndetic recombinants involving chromosome arms 1DS and 1RS derived from the wheat-rye translocation 1DL-1RS, and one 1RS recombinant derived from 1BL-1RS were characterised by cytological, biochemical and molecular methods. Analysis of isozyme markers showed that recombination had involved different breakpoints along the 1DS arm. The gene order Tri-D1 - Per-D1 - Gpi-D1 - Gli-D1 was established on chromosome 1DS, and this is consistent with the gene order known to occur on 1BS. The use of three molecular probes for loci on 1RS confirmed one of the recombinants obtained from the 1BL-1RS translocation, and two of the three recombinants obtained from the 1DL-1RS translocation. These two recombinant chromosomes appear to have approximately reciprocal structures and may prove of direct benefit to wheat breeders as they retain the stem rust resistance of the parental translocation but have recovered some of the 1D encoded proteins which are absent in 1DL-1RS lines and which are thought to affect dough quality. A 5S RNA site was discovered on chromosome arm 1DS, probably reflecting the homoeologous relationship of this chromosome with 1BS. Segregational analysis indicated that some of the homoeologous wheat-wheat exchanges probably involved more than a single allosyndetic event. PMID- 24240853 TI - Selection for yield and yield components in the early generations of a potato breeding programme. AB - A number of unselected potato (Solanum tuberosum L.) clones were grown at two locations (a seed site and a ware site) in three consecutive years. The repeatability of total yield and yield components in the first two clonal years was compared with the same characters recorded in the third clonal year. Selection for yield in the first clonal year was only marginally more effective than a random reduction in number of genotypes, while selection in the second clonal year appeared to be somewhat more effective as judged by performance in the third clonal year. The inefficiency of selection in the first clonal year was ascribed, at least in part, to the inaccuracy of yield assessment as well as the "carry-over" effect of the mother tubers. Correlations of total yield were higher between different years in the same location than between different locations. Selection under growing conditions suitable for production of seed tubers tended to result in selection of early maturing clones which would not necessarily be optimal for ware growing conditions. PMID- 24240854 TI - Genetic pollution and number of matings in a black honey bee (Apis mellifera mellifera) population. AB - In the south-east of France, local honey bees possess only the B allele at the MDH locus, whereas the races which are usually imported into this area do not have this allele. The proportion of non-B genes in a sample of drones was used to measure the "genetic pollution" in the local population. Within the course of a breeding scheme of local bees, 99 queens, whose genotypes are BB, were naturally mated between April 25 and June 10, 1985 at la Tave (Gard, France). Twenty daughters-workers of each queen were analysed at the MDH locus. The frequency of the B allele in drones that mated with these queens is estimated by the proportion of workers with genotype BB and the genetic pollution by the cumulated frequency of the other alleles. The sampling variances of these frequencies involve a coefficient which is a function of the average number of drones mated with a queen. This latter parameter is estimated through the maximum likelihood method. In addition to the three well-known alleles, a rare allele (frequency=0.0055), possibly equivalent to the S1 allele described by Badino et al. (1983), has been found in three different colonies. Cumulating the frequencies of the non-B alleles results in an estimation of the genetic pollution equal to 0.0394 (+/-0.0071). This low value allows us to proceed to the next step of the selection project. The mean number of drones mated to a queen is 12.4 with a (10.4-19.3) confidence interval at the 90% level. PMID- 24240855 TI - Diallel and generation means analyses for the components of resistance to Cercospora arachidicola in peanut. AB - The inheritance of the components of partial resistance to Cercospora arachidicola Hori in peanut (Arachis hypogaea L.) was examined in two five-parent diallels and in the six generations of two single crosses in greenhouse tests. The Griffing (1956) analysis indicated general combining ability (GCA) to be of most importance, yet large ratios of SCA/GCA sum of squares suggested nonadditive genetic variance as well. Reciprocal effects were found for lesion area and lesion number/10 cm(2) leaf area. The importance of nonadditive genetic variance was substantiated by the lack of fit for the additive-dominance model in the Hayman's analysis (1954 a, b). Further evidence from the Hayman's analysis indicated that epistasis may be important in determining the inheritance of some of the components of resistance. Additive gene effects alone accounted for the genetic variability observed among the generation means from two single crosses for all components of resistance except latent period. There was evidence that epistasis was an important mode of gene action for the inheritance of latent period. PMID- 24240856 TI - Use of an interspecific hybrid in identifying a new allelic specificity generated at the self-incompatibility locus after inbreeding in Lycopersicon peruvianum. AB - An interspecific hybrid between Lycopersicon esculentum (?) and L. peruvianum has been raised by embryo rescue in vitro and used to confirm the presence of a new S allelic specificity in its inbred L. peruvianum parent, a plant derived by enforced bud self-pollination of a self-incompatible clone with the genotype S 1 S 2. The inbred plant showed breeding behavior characteristic of both S 2 and a second specificity which was not S 1, S 2, S 3 or S f. Two-dimensional gel electrophoresis of stylar proteins, however, showed only a single typical S associated component with the Mr and pI characteristic of S2. The alteration in specificity, therefore, was not associated with a detectable change in an S associated protein. The F1 interspecific hybrid showed intermediacy of vegetative and reproductive characters, relatively high fertility and full self incompatibility. Backcrossing to L. esculentum produced only abortive seeds requiring embryo culture. Backcrosses to L. peruvianum produced a very low proportion of filled germinable seeds. Pollen of the hybrid showed superior viability and tube growth rate compared with pollen of the two parent plants. PMID- 24240857 TI - Regulatory effects of homoeologous chromosome arms on wheat proteins at two developmental stages. AB - Two-dimensional gel electrophoresis was conducted on denatured proteins of the 10 day-old first leaf (1F stage) of 18 homoeologous ditelosomic (DT) lines of wheat cultivar 'Chinese Spring'. The observations, compared to the euploid control and relative to previous data found on 7-day-old etiolated seedlings (G7 stage) of the same lines lead to the following statements: 1) the structural genes of 24 spots can be assigned to 12 chromosome arms; 2) regulatory effects are completely different between the 1F and the G7 stages which may indicate that the regulation of protein amounts is often stage-specific; 3) no case of complete gene dosage compensation is observed among 4 groups of hypothesized homoeoallelic products; 4) homoeologous DT lines do not manifest similar effects which suggest the absence of homoeology for the detected regulatory effects. PMID- 24240858 TI - Nuclear-mitochondrial interactions in cytoplasmic male-sterile sorghum. AB - Variation in mitochondrial genome organization and expression between male fertile and sterile nuclear-cytoplasmic combinations of sorghum has been examined. Cytoplasmic genotypes were classified into eleven groups on the basis of restriction endonuclease digestion of mitochondrial DNA (mtDNA) and five groups on the basis of mitochondrial translation products. These cytoplasms were further characterized by hybridization of specific gene probes to Southern blots of EcoRI digested mtDNA, and identification of the fragment location of four mitochondrial genes. Variation was observed in the genomic location and copy number of the F1 ATPase alpha-subunit gene, as well as the genomic location and gene product of the cytochrome c oxidase subunit I gene. The effect of nuclear genotype on mitochondrial genome organization, expression and the presence of two linear plasmid-like mtDNA molecules was examined. Our results indicate that nuclear-mitochondrial interactions are required for regulation of mitochondrial gene expression. When a cytoplasm is transferred from its natural to a foreign nuclear background some changes in the products of in organello mitochondrial protein synthesis occur. In a number of cytoplasmic genotypes these changes correlate with the expression of cytoplasmic male sterile phenotype, suggesting a possible molecular basis for this mutation. PMID- 24240859 TI - Investigations on an interspecific hybrid involving three species of the genus Beta, with special reference to isozyme polymorphism. AB - A tetraploid (2n=36) interspecific hybrid was obtained involving three species belonging to three different sections of Beta. The hybrid was highly sterile and did not show apomixis. At meiosis, up to nine bivalents were observed, most probably resulting from autosyndesis of the chromosomes of Beta lomatogona. For nine isozyme systems, individual enzyme expression was investigated in the parental species and in the hybrids. No silencing of genes or genomes was observed. In the case of some polymeric enzymes interspecific heteropolymers could be detected. PMID- 24240860 TI - Somatic embryogenesis and plantlet regeneration in the genus Secale : 1. Somatic embryogenesis and organogenesis from cultured immature embryos of five wild species of rye. AB - A tissue culture of five wild species of the Secale genus, i.e., S. africanum (Stapf.), S. ancestrale (Zhuk.), S. kuprianovii (Grossh), S. segetale (Rosher.), and S. vavilovii (Grossh), from immature embryos of sizes (stages) varying between 1.0 mm to 3.0mm, cultured on MS (1962) mineral nutrient medium supplemented with 0.62 mg/1-5.0 mg/1 of 2,4-D, was established. Initially various types of callus were observed and a correlation between genotype, size of explant and 2,4-D concentration was found. The best embryogenic response was observed when explants were smaller than 1.0 mm. Induction of somatic embryogenesis of 2.0 mm-3.0 mm explants required a higher concentration of 2,4-D. Most embryoids were formed in the presence of 5.0 mg/l of 2,4-D. Secale africanum and S. kuprianovii appeared to have the highest embryogenic capacity among the five investigated species. For embryoids germination to plantlets the MS medium supplemented with GA3 and cytokinins was used. Ultimately, out of the 932 regenerants obtained 364 originated from somatic embryogenesis. PMID- 24240861 TI - Peptidases A, B, C, D and S in the American mink: polymorphism and chromosome localization. AB - An electrophoretic analysis of peptidases was carried out in a population of American mink. Based on substrate and tissue specificities, as well as subunit composition, homologies were established between mink peptidases A, B, C, D and S and human peptidases. Polymorphism for peptidases B and D was demonstrated for minks of three coat colour types. Breeding data indicated that the peptidase variations are under the control of allele pairs at distinct autosomal loci designated as PEPB and PEPD, respectively. Using a panel of American mink-Chinese hamster hybrid clones, the gene for PEPB was assigned to mink chromosome 9. PMID- 24240862 TI - Genetic analysis of gliadin-encoding genes reveals gene clusters as well as single remote genes. AB - Analysis of F2 grains from two different crosses has revealed a complex organization of the family of gliadin-coding genes located on chromosomes of the first homoeological group in hexaploid wheat. Chromosome 1A of variety 'Bezenchukskaya 98' was found to carry at least five gliadin-coding genes of which three genes form a cluster controlling the synthesis of the GLD1A1 block. Two additional genes are located on the both sides of this cluster and recombine with it at frequencies of 5+/-1.3% and 13+/-2.9%. Gliadinencoding genes recombining with the main clusters were also found on chromosomes 1B and 1A in the 'Bezenchukskaya 98' and 'Saratovskaya 210' varieties, respectively. In 'Chinese Spring', widely used in genetic studies, we discovered a recombination between genes located on chromosome 1A and controlling the synthesis of omega- and gamma-gliadins. Varieties and biotypes of one variety may differ by the presence or absence of such "selfish" (not included in clusters) gliadin components. The similarity of organization of prolamine-coding genes on chromosomes in different cereals is considered. PMID- 24240863 TI - In vitro response of leaf tissues from Lolium multiflorum - a comparison with leaf segment position, leaf age and in vivo mitotic activity. AB - Immature gramineous leaves provide a convenient system for comparing the response of cells in culture with their state of differentiation. Callusing frequency is compared with leaf segment position, leaf age and in vivo mitotic activity in Lolium multiflorum. (1) In a succession of one millimeter sections from the immature leaf base, callus was formed from the first and second sections but not the third or subsequent sections. The frequency of those explants callusing decreased with distance from the base of the leaf and with leaf age (or leaf extension growth). (2) In vivo, the proportion of cells in mitosis declined from around 10-14% at the base of young leaves to zero at 5 mm from the base and beyond. Mitotic activity also declined in leaves as they aged, and dividing cells were not observed in leaves 30 days from initiation or older. (3) A high frequency of callus formation was associated with a high mitotic index in the explant. But for corresponding mitotic indices, cells further away from the leaf base were less responsive in culture. (4) It is proposed that cells are becoming differentiated even in highly meristematically active regions of the leaf and concomitantly losing their ability to respond in culture. PMID- 24240864 TI - Genetic improvement of Egyptian henbane, Hyoscyamus muticus L. through induced tetraploidy. AB - Induced autotetraploids with high pollen and seed fertility have been developed in a medicinally important Solanaceous plant: Hyoscyamus muticus (2n=28). The colchiploids are vigorous and the increase in all the determinate parts - plant height, size and thickness of leaves, cell, pollen, seed and flower size - along with an increase in alkaloid content has been achieved. The overall improvement in the colchiploids has the advantage of enhancing nearly 1.5 times the production potential of the economic product - the total alkaloids. Although the seed is not the ultimate economic product in this species, it is still required for propagation. The seed fertility in the colchiploids improved because of reduction in quadrivalent frequency and subsequent balanced anaphase separation. PMID- 24240865 TI - Improved in vitro selection of nitrate reductase-deficient mutants of Nicotiana plumbaginifolia. AB - The use of increasing knowledge on regulation of nitrate reductase activity in Nicotiana cell cultures is the basis for the described optimization of in vitro selection for nitrate reductase-deficient mutants by screening for chlorate resistance. Selection was carried out on haploid mesophyll protoplast-derived cell cultures of Nicotiana plumbaginifolia. It is demonstrated that revised selection results in high variant detectability and increased variant confirmability in comparison with the hitherto used selection scheme. PMID- 24240866 TI - Self-incompatibility and interspecific incompatibility: relationships in intra- and interspecific crosses of Zinnia elegans Jacq. and Z. angustifolia HBK (Compositae). AB - Intraspecific and reciprocal interspecific crosses involving Zinnia angustifolia clones and Z. elegans lines showed that in both species, sporophytic self incompatibility (SI) systems were present. Intensity of SI varied among clones and lines, and high self seed set was associated with a concomitant decrease in callose fluorescence in papillae and pollen tubes. Incomplete stigmatic inhibition of pollen germination and tube growth was observed in reciprocal interspecific crosses and associated with callose synthesis, suggesting S-gene activity. Seed set and progeny obtained following Z. angustifolia*Z. elegans matings was comparable to intraspecific compatible matings of Z. angustifolia although the rate of pollen tube growth through the style was slower. In Z. elegans * Z. angustifolia matings, additional prezygotic barriers were present and acted between pollen tube penetration of the stigma and syngamy. SI X SI interspecific incompatibility was essentially unilateral, with no embryos or progeny obtained when Z. elegans was the pistillate parent. It was hypothesized that nonfunctioning of Z. elegans * Z. angustifolia crosses was due to S-gene expression at the stigmatic surface and to other isolating mechanisms in the stylar or ovarian transmitting tissue. PMID- 24240867 TI - X chromosome origin of a supernumerary-like segment in Blatella germanica. AB - An extraneous heterochromatic segment was discovered in a strain selected for a large-body trait. Derivation from the X chromosome is indicated by its behavior at metaphase I and association with the X and nucleolus in early prophase I. The segment does not pair with the X. Association with a mid-length bivalent is attributed to fusion of heterochromatin. Centromeric activity of small fragments, independent of, but apparently derived from, the X, is also reported. PMID- 24240868 TI - Natural variation in PTB1 regulates rice seed setting rate by controlling pollen tube growth. AB - Grain number, panicle seed setting rate, panicle number and grain weight are the most important components of rice grain yield. To date, several genes related to grain weight, grain number and panicle number have been described in rice. However, no genes regulating the panicle seed setting rate have been functionally characterized. Here we show that the domestication-related POLLEN TUBE BLOCKED 1 (PTB1), a RING-type E3 ubiquitin ligase, positively regulates the rice panicle seed setting rate by promoting pollen tube growth. The natural variation in expression of PTB1 which is affected by the promoter haplotype and the environmental temperature, correlates with the rice panicle seed setting rate. Our results support the hypothesis that PTB1 is an important maternal sporophytic factor of pollen tube growth and a key modulator of the rice panicle seed setting rate. This finding has implications for the improvement of rice yield. PMID- 24240869 TI - Lasting alterations of the sodium current by short-term hyperlipidemia as a mechanism for initiation of cardiac remodeling. AB - Clinical and animal studies indicate that increased fatty acid delivery to lean tissues induces cardiac electrical remodeling and alterations of cellular calcium homeostasis. Since this may represent a mechanism initiating cardiac dysfunction during establishment of insulin resistance and diabetes or anaerobic cardiac metabolism (ischemia), we sought to determine if short-term exposure to high plasma concentration of fatty acid in vivo was sufficient to alter the cardiac sodium current (INa) in dog ventricular myocytes. Our results show that delivery of triglycerides and nonesterified fatty acids by infusion of Intralipid + heparin (IH) for 8 h increased the amplitude of INa by 43% and shifted its activation threshold by -5 mV, closer to the resting membrane potential. Steady state inactivation (availability) of the channels was reduced by IH with no changes in recovery from inactivation. As a consequence, INa "window" current, a strong determinant of intracellular Na+ and Ca2+ concentrations, was significantly increased. The results indicate that increased circulating fatty acids alter INa gating in manners consistent with an increased cardiac excitability and augmentation of intracellular calcium. Moreover, these changes could still be measured after the dogs were left to recover for 12 h after IH perfusion, suggesting lasting changes in INa. Our results indicate that fatty acids rapidly induce cardiac remodeling and suggest that this process may be involved in the development of cardiac dysfunctions associated to insulin resistance and diabetes. PMID- 24240870 TI - Temporal hemodynamic and histological progression in Sugen5416/hypoxia/normoxia exposed pulmonary arterial hypertensive rats. AB - We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3~5 wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration. PMID- 24240871 TI - Nitric oxide suppresses vascular voltage-gated T-type Ca2+ channels through cGMP/PKG signaling. AB - Recent reports have noted that T-type Ca2+ channels (CaV3.x) are expressed in vascular smooth muscle and are potential targets of regulation. In this study, we examined whether and by what mechanism nitric oxide (NO), a key vasodilator, influences this conductance. Using patch-clamp electrophysiology and rat cerebral arterial smooth muscle cells, we monitored an inward Ba2+ current that was divisible into a nifedipine-sensitive and -insensitive component. The latter was abolished by T-type channel blocker and displayed classic T-type properties including faster activation and steady-state inactivation at hyperpolarized potentials. NO donors (sodium nitroprusside, S-nitroso-N-acetyl-dl penicillamine), along with activators of protein kinase G (PKG) signaling, suppressed T-type currents. Inhibitors of guanylyl cyclase/PKG {1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and KT5823, respectively}, had no effect on basal currents; KT5823 did, however, mask T-type Ca2+ channel current inhibition by NO/PKG. Functional experiments confirmed an inhibitory effect for NO on the T-type contribution to cerebral arterial myogenic tone. Cumulatively, our findings support the view that T-type Ca2+ channels are a regulatory target of vasodilatory signaling pathways. This targeting will influence Ca2+ dynamics and consequent tone development in the cerebral circulation. PMID- 24240873 TI - Comparison of Surgical Outcomes Between Phacocanaloplasty and Phacotrabeculectomy at 12 Months' Follow-up: A Longitudinal Cohort Study. AB - PURPOSE: To compare operative outcomes of patients after phacocanaloplasty and phacotrabeculectomy through 12 months' follow-up. DESIGN: Retrospective, nonrandomized, comparative case series. MATERIALS AND METHODS: We included 36 eyes of 36 patients with open-angle glaucoma who underwent combined phacoemulsification and canaloplasty (phacocanaloplasty) and 41 eyes of 41 patients with open-angle glaucoma who underwent combined phacoemulsification and trabeculectomy with mitomycin C (phacotrabeculectomy) with 12 months' of postoperative follow-up. All surgeries were performed by a single surgeon (R.S.A.) between January 2007 and May 2011. MAIN OUTCOME MEASURES: Failure was based on intraocular pressure (IOP; >18 or <4 mm Hg at 1 y), second operative procedure (any eye requiring reoperation), or decrease in visual acuity by 0.20 logMAR. Change in IOP, visual acuity (VA), glaucoma medications, and complication rates at 12 months were analyzed. RESULTS: There were no differences in demographics other than the sex between the groups. There were also no significant differences in previous surgery or in preoperative VA, IOP, or use of glaucoma medications between the groups, though the phacotrabeculectomy group had a higher preoperative IOP at baseline and a larger SD. Both groups showed significant reduction in IOP from baseline at every time point (P<0.001). No significant difference in mean IOP at 12 months was found, with a mean of 14.1+/ 4.4 mm Hg in the phacocanaloplasty group and 11.8+/-5.4 mm Hg in the phacotrabeculectomy group (P=0.07). The phacotrabeculectomy group showed a significantly greater median absolute (8 vs. 5 mm Hg) and percent (40% vs. 28%) reduction in IOP at 12 months (P=0.02). Postoperative glaucoma medication use was similar between the 2 groups.Overall failure rates at 1 year were comparable between the 2 groups: 22% for phacocanaloplasty versus 20% for phacotrabeculectomy (P=0.79). Phacotrabeculectomy eyes experienced more visual failures (5% vs. 0%, P=0.50), whereas phacocanaloplasty experienced more IOP failures (17% vs. 12%, P=0.75). No difference in operative failure rate was found between the phacocanaloplasty and phacotrabeculectomy groups (6% vs. 5%, P=1.00) and this held after controlling for covariates. Final VA was not statistically different between the 2 groups. CONCLUSIONS: Phacocanaloplasty and phacotrabeculectomy both achieved significant reduction in IOP and improvement in VA at 12 months with comparable success rates. Phacotrabeculectomy achieved a statistically greater median percentage decrease in IOP, but the 2 procedures resulted in comparable mean IOP at 12 months. PMID- 24240874 TI - Anxiety and Depression are More Prevalent in Primary Angle Closure Glaucoma Than in Primary Open-Angle Glaucoma. AB - PURPOSE: The aim of this study was to assess the prevalence of psychological disturbances and personality traits in primary angle closure glaucoma (PACG) and primary open-angle glaucoma (POAG) patients. METHODS: A sample of 50 PACG patients, 50 POAG patients, and 50 normal controls were enrolled in this study. All the participants were asked to complete the following questionnaires: Self rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Eysenck Personality Questionnaire (EPQ), and Defense Style Questionnaire (DSQ). Analysis of variance and t test were used to compare the subscores between the groups. RESULTS: The scores of SAS and SDS were higher in glaucoma patients than in controls, whereas the PACG group had a higher score for both scales (48.44+/ 9.90; 53.64+/-9.74) than the POAG group (42.62+/-9.00, P=0.034; 49.02+/-11.47, P=0.131) and control group (37.10+/-6.08, P=0.000; 38.86+/-6.64, P=0.000). Taking an SAS score of >=45 and an SDS score of >=50 as cut-offs, the prevalence of anxiety and depression in the PACG group (66.0%, 56.0%) was significantly higher than in the POAG group (44.0%, P=0.002; 40.0%, P=0.033) and control group (16.0%, P=0.000; 10.0%, P=0.000). The values of psychoticism and neuroticism in EPQ for the PACG and POAG groups were significantly higher than those for controls (P<0.05). In DSQ, PACG and POAG patients adopted immature and neurotic defense styles more often than controls (P<0.05). No significant differences were found between male and female participants in all the questionnaires used (P>0.05). CONCLUSIONS: Significant differences were found between primary glaucoma patients and normal controls in psychiatric questionnaires, whereas the level of anxiety and depression was found to be significantly higher in PACG patients than in POAG patients and controls. PMID- 24240875 TI - Fornix-based Trabeculectomy With Mitomycin C Using the Horizontal Conjunctival Suture Technique. AB - PURPOSE: The aim of this study was to determine the safety, efficacy, and bleb morphology of fornix-based trabeculectomy with mitomycin C using the horizontal suture technique. MATERIALS AND METHODS: A retrospective noncomparative case series of 79 eyes of 69 patients, who underwent fornix-based trabeculectomy with mitomycin C, was studied. Conjunctival closure of all eyes was with the horizontal suture technique using 10-0 nylon suture to prevent bleb leakage and improve bleb morphology posttrabeculectomy. The main outcome measures were the bleb morphology, outcome of surgery, and complications posttrabeculectomy. RESULTS: At a mean follow-up period of 25.5+/-9.3 months, 65 eyes (82.3%) had diffuse blebs with horizontal extent between 2 and 4 clock hours. Low-lying bleb was found in 35 eyes (44.3%), whereas 39 eyes (49.4%) had moderately elevated bleb. Fifty-one eyes (64.6%) had complete success, 18 eyes (22.8%) had qualified success, whereas 10 eyes (12.6%) were classified as treatment failures. Overall, 87.4% of the patients had a successful outcome. Corneal encroachment/overhanging blebs were found in 3 eyes (3.8%). Bleb leakage was found in 7 eyes (8.8%). There was overfiltration in 2 eyes (2.5%) with shallow anterior chamber. CONCLUSIONS: The horizontal suture technique is an easily applied, less time-consuming technique that gives excellent bleb morphology with few complications in the long term. PMID- 24240876 TI - Outcome Measures in Glaucoma: A Systematic Review of Cochrane Reviews and Protocols. AB - PURPOSE: In clinical trials, the selection of appropriate outcomes is crucial for the assessment of whether one intervention is better than another. Selection of inappropriate outcomes can compromise the utility of a trial. However, the process of selecting the most suitable outcomes to include can be complex. Ideally, glaucoma trials aim to evaluate important outcomes for clinicians and patients. A high variability in the selection of outcomes suggests that there is no consensus on how best to evaluate the effect of glaucoma interventions. Further, it makes evidence synthesis difficult. The purpose of this review is to determine the extent of clinical outcome measures used in published glaucoma Cochrane Reviews and Protocols. METHODS: A systematic review was conducted (up to February 2012) of all Cochrane Reviews and Protocols related to glaucoma interventions and published in English language. All clinical, patient-reported, as well as economic outcomes were included. RESULTS: In the Cochrane Library there were 12 Reviews and 9 Protocols on glaucoma. A total of 118 clinical outcomes were reported. Intraocular pressure was the most commonly used clinical outcome (n=40), and it was used in 11 Reviews and 5 Protocols. Intraocular pressure was evaluated in many different ways; the most common one was a composite definition of success. Safety outcomes were also frequently reported. Visual field progression or change was reported in 6 reviews and 3 protocols, but in 13 different ways. Patient-reported quality-of-life measures were chosen as main outcome measure in 1 Review. CONCLUSIONS: There is a large variability in outcomes selected in glaucoma Cochrane Reviews and Protocols. This heterogeneity in outcome selection impairs the ability for evidence synthesis. There is an urgent need for standardization of outcomes used in glaucoma trials. PMID- 24240877 TI - A comparison of optic nerve head topographic measurements by Stratus OCT in patients with macrodiscs and normal-sized healthy discs. AB - PURPOSE: To evaluate and compare optic nerve head parameters and retinal nerve fiber layer (RNFL) thickness between large discs and normal-sized vital discs using Stratus optical coherence tomography (OCT). METHODS: A total of 293 healthy eyes (145 with macrodisc and 148 with normal-sized disc) were enrolled in the study. After a complete ophthalmic evaluation, measurement of optic nerve head parameters and RNFL thickness using OCT was performed in all subjects. Optic disc areas larger than 2.80 mm were accepted as macrodiscs. All OCT parameters were compared between normal-sized discs and macrodiscs. RESULTS: Participants' mean age was 46.5+/-10.6 years (range, 13 to 74 y). Average optic disc areas were 2.19+/-0.29 and 3.02+/-0.29 mm in the normal and the macrodisc groups, respectively. The optic disc area (P<0.0001), the cup area (P<0.0001), the horizontal cup disc ratio (P<0.0001), the vertical cup disc ratio (P<0.0001), and the cup disc area ratio (P<0.0001) were found to be significantly different in the macrodisc group and the control group. Rim areas (P=0.57) and RNFL thicknesses (inferior, superior, and mean) were found to be similar in both groups (P=0.75, 0.65, 0.85, respectively). CONCLUSIONS: A macrodisc may have a macrocup and should not be misdiagnosed as glaucoma. The present study showed that macrodiscs are identical to normal-sized discs in terms of rim area and RNFL thickness. We suggest that these 2 OCT parameters can help to differentiate a healthy macrodisc from a glaucomatous optic disc. PMID- 24240878 TI - Bilateral juvenile onset primary open-angle glaucoma among keratoconus patients. AB - PURPOSE: To report the occurrence of juvenile open-angle glaucoma (JOAG) in patients with keratoconus. PATIENTS AND METHODS: In this observational case series we report 6 eyes of 3 patients with keratoconus who had concomitant JOAG. Corneal topography, intraocular pressure, gonioscopic, and fundus findings were recorded for all the eyes. RESULTS: All 3 patients presented with corneal ectasia, high intraocular pressure, and advanced glaucomatous damage and had no family history of glaucoma or keratoconus. Two of the 3 patients needed collagen cross-linking with riboflavin for progression of keratoconus and trabeculectomy for control of intraocular pressure. One of the patients also underwent a lamellar keratoplasty for keratoconus. CONCLUSIONS: This is the first case series pointing toward a possible association of JOAG with keratoconus and highlights the importance of a thorough workup of glaucoma in patients with keratoconus. PMID- 24240879 TI - Diagnostic validity of macular ganglion cell-inner plexiform layer thickness deviation map algorithm using cirrus HD-OCT in preperimetric and early glaucoma. AB - PURPOSE: To evaluate the diagnostic validity of macular ganglion cell-inner plexiform layer (mGCIPL) thickness deviation map algorithm using Cirrus high definition-optical coherence tomography to discriminate between normal controls and patients with preperimetric or early glaucoma. PATIENTS AND METHODS: Seventy two normal controls, 37 patients with preperimetric glaucoma and 70 patients with early glaucoma were enrolled. mGCIPL thickness and peripapillary retinal nerve fiber layer (pRNFL) thickness were measured by Cirrus high definition-optical coherence tomography. Areas showing abnormal color coding were obtained by customized Image J software calculating the number of abnormal superpixels at 1% and 5% level in each deviation map of measurements (GCIPL-DM1, GCIPL-DM5, RNFL DM1, RNFL-DM5). The area under the receiver operating characteristic curve (AROC) of each parameter was calculated to provide diagnostic ability between normal controls and patients with preperimetric or early glaucoma. RESULTS: AROCs of the deviation map algorithms were higher than those of other parameters. Parameter with the best AROC was the GCIPL-DM5 (0.920 and 0.968) in both preperimetric and early glaucoma. The sensitivities of the GCIPL-DM5 at 80% and 95% specificities were 92% and 68% in preperimetric glaucoma and 98% and 90% in early glaucoma, respectively. Pairwise comparisons between AROCs of parameters from deviation map algorithms did not show statistically significant differences. CONCLUSIONS: mGCIPL thickness deviation map showed good diagnostic ability in detecting preperimetric and early glaucoma, and it was comparable with pRNFL thickness deviation map. Our findings suggest that it can be an important parameter in detecting subtle glaucomatous structural change. PMID- 24240880 TI - Application of the ISNT Rule to Neuroretinal Rim Thickness Determined Using Cirrus HD Optical Coherence Tomography. AB - PURPOSE: The study investigated the applicability of the inferior>=superior>=nasal>=temporal neuroretinal rim thickness (ISNT) rule to rim thickness measured using Cirrus high-definition spectral-domain optical coherence tomography (Cirrus HD-OCT) in healthy eyes and eyes with glaucoma. METHODS: Rim thicknesses of 4 quadrants were investigated using the rim thickness curve of Cirrus HD-OCT for 40 eyes with mild glaucoma (mean deviation >= -6 dB), 40 eyes with moderate to advanced glaucoma (mean deviation < -6 dB), and 80 healthy eyes (control group). The relative amount of rim loss in each quadrant in the glaucoma group compared with the control group was calculated. The ISNT rule was considered intact if there was a gradual decrease in rim thickness in the order of inferior>=superior>=nasal>=temporal quadrants. RESULTS: The ISNT rule was intact in 13%, 18%, and 8% of eyes in the control, mild, and moderate to advanced glaucoma groups, respectively, and the distribution was not significantly different among the 3 groups (P>0.05). Relative rim loss in the inferior quadrant of the moderate to advanced glaucoma group (63.8%) was greater than that of the mild glaucoma group (53.6%; P=0.010), whereas rim loss in other quadrants was not significantly different between the 2 groups (P>0.05). CONCLUSIONS: The ISNT rule with rim thickness measured using Cirrus HD-OCT has limited clinical value in the diagnosis of glaucoma. There is a topographic difference in inferior rim loss according to the stages of glaucomatous damage. PMID- 24240881 TI - Safety and Efficacy of Benzalkonium Chloride-optimized Tafluprost in Japanese Glaucoma Patients With Existing Superficial Punctate Keratitis. AB - PURPOSE: To evaluate the safety and efficacy of benzalkonium chloride (BAK) optimized tafluprost (with a BAK concentration reduced from 0.01% to 0.001%) in glaucoma patients with existing superficial punctate keratitis (SPK). PATIENTS AND METHODS: A prospective, multicenter, open-label study was designed to compare BAK-optimized tafluprost administered over 12 weeks relative to other preserved prostaglandin analogs previously administered in Japanese glaucoma patients. Thirty patients with SPK graded at <6 points by area density (AD) scoring in 1 eye were recruited. The primary outcome measure was change in AD score at 12 weeks after the switch in treatment compared with that at baseline. Secondary outcome measures included changes in tear film breakup time (TBUT), hyperemia score, and intraocular pressure (IOP). Four patients were excluded from analysis because of treatment discontinuation. RESULTS: Mean AD score+/-SD decreased significantly from 3.4+/-0.9 to 1.8+/-1.8 after the switch (P<0.0001). Mean TBUT increased significantly from 6.3+/-3.3 to 8.0+/-4.2 seconds (P<0.01). Mean hyperemia score remained unchanged, whereas mean IOP decreased significantly from 15.6+/-2.6 to 14.4+/-2.0 mm Hg (P<0.01). For patients previously treated with BAK preserved latanoprost (n=17) or bimatoprost (n=2), mean AD score decreased significantly from 3.4+/-0.9 to 1.8+/-1.8 (P<0.01) and mean TBUT increased significantly from 6.4+/-3.6 to 8.2+/-4.3 seconds (P<0.01); no such changes were apparent for patients previously treated with sofZia-preserved travoprost (n=7). CONCLUSIONS: BAK-optimized tafluprost is a treatment option to improve the condition of the ocular surface and to maintain IOP control in glaucoma patients with existing SPK who have been previously treated with other BAK-preserved prostaglandin analogs. PMID- 24240882 TI - Using a collagen matrix implant (Ologen) versus mitomycin-C as a wound healing modulator in trabeculectomy with the Ex-PRESS mini glaucoma device: a 12-month retrospective review. AB - PURPOSE: To compare outcomes between patients undergoing trabeculectomy with an Ex-PRESS mini glaucoma device using mitomycin-C (MMC) to those undergoing the same procedure using a subconjunctival collagen matrix implant (Ologen). MATERIALS AND METHODS: All patients underwent a trabeculectomy using an Ex-PRESS shunt. A total of 49 eyes of 37 patients received Ologen, and 50 eyes of 48 patients received MMC. Postoperative data were reviewed over 12 months. Outcomes included mean intraocular pressure (IOP), rate of success in achieving a target IOP (with and without antiglaucoma medications), number of medications used, and rates of complications/reoperations. RESULTS: The mean preoperative IOP was 24.98 mm Hg for the MMC group, and 23.24 mm Hg for the Ologen group (P=0.3). At 12 months postoperatively, the mean IOP was 12.1 mm Hg for the MMC group, and 13.12 mm Hg for the Ologen group (P=0.34). At 12 months, the rate of achieving an IOP<=21 mm Hg off medications (unqualified success) was 84% for the MMC group, and 86% for the Ologen group. There was no statistically significant difference between either group for the rates of achieving a specified postoperative IOP either with (qualified success) or without medications. There was no statistically significant difference between the 2 groups in the mean number of postoperative medications required. Both groups had similar rates of complications, and 1 patient in the MMC group lost light perception after a suprachoroidal hemorrhage. CONCLUSIONS: Our results suggest that ologen provides similar rates of surgical success as MMC for patients undergoing a filtering procedure using an Ex-PRESS mini glaucoma device. PMID- 24240883 TI - Risk factors for developing glaucoma among patients with uveitis: a nationwide study in Taiwan. AB - PURPOSE: To investigate the incidence and risk factors for developing ocular hypertension or glaucoma needing treatment among uveitis patients in Taiwan. METHODS: The nationwide database-derived retrospective cohort study was designed using Taiwan's National Health Insurance Research Database. From 1 million representative samples randomly selected from the beneficiaries of the National Health Insurance program, all patients with a diagnosis of uveitis were identified. Only newly onset uveitis patients who were diagnosed after January 1, 2002 and had no prior diagnosis of glaucoma were included in the study, and were followed up until December 31, 2008 or the last day that they were covered by the program. A patient was defined as having glaucoma as soon as both a diagnosis of glaucoma or ocular hypertension as well as a claim for medical or surgical treatment of glaucoma was found. Risk factors for developing glaucoma at the time of, or after the uveitis incidence were evaluated and discussed. RESULTS: Initially, 5757 newly diagnosed uveitis patients were enrolled in the study. Of these patients, 488 (8.5%) were also diagnosed with glaucoma at the time of uveitis incidence. Patients aged 17 to 64 years, of male sex and diagnosed with anterior uveitis were more likely to have glaucoma at the time of the uveitis incidence. Among the remaining 5269 patients, 351 (6.7%) patients developed glaucoma during the follow-up period. Significant risk factors included increasing age, having been diagnosed with anterior uveitis, having more than an average number of ophthalmic claims within the first 3 months, and complications with corneal edema. A stratified analysis showed that having a history of receiving intraocular surgery is also a risk factor for the development of glaucoma among adult patients. CONCLUSIONS: The development of glaucoma in uveitis patients is noteworthy and is associated with several demographic and clinical factors. To minimize the visual impairment caused by uveitis-related glaucoma, clinicians should pay more attention to those uveitis patients who are at high risk for developing glaucoma. PMID- 24240884 TI - Methyl-sulfonyl-methane (MSM)-induced acute angle closure. AB - PURPOSE: To report the first case of presumed bilateral acute angle closure (AAC) secondary to ingestion of the dietary supplement, methyl-sulfonyl-methane (MSM). PATIENT: A 35-year-old woman presented with bilateral AAC 1 week after starting multiple dietary supplements, one of which contained MSM. Ultrasound biomicroscopy demonstrated bilateral anterior rotation of the iris-lens diaphragm, ciliary body edema, and choroidal effusion. Four days after discontinuation of the supplements, her angle closure and uveal effusion resolved, and her best-corrected vision recovered to 20/20 bilaterally. DISCUSSION: Sulfa-based drugs have been reported to cause AAC, choroidal effusion, and ciliary body edema. In our patient, the coincidence of bilateral AAC with choroidal and ciliary body effusion that began 1 week after starting dietary supplements was suspicious for drug-induced AAC. The dietary supplement Basic Detox Nutrients contains MSM, the only constituent in the patient's medication list with a sulfonyl moiety. Given the similarities in chemical structure and clinical presentation, we postulate that MSM induces AAC in a manner similar to mechanisms previously described for other sulfa-based drugs. CONCLUSIONS: As MSM continues to be used and studied for its anti-inflammatory and antioxidative properties, investigators and marketers will need to be cognizant of its potential to cause AAC and provide proper warning to consumers. PMID- 24240885 TI - Angle closure associated with a cobblestone iris configuration: clinical and imaging description. AB - PURPOSE: The purpose of the study was to report a patient with primary angle closure associated with a different nonpupillary block mechanism in which an abnormally thick peripheral iris assumes a cross-sectional shape resembling a cobblestone. METHODS: This is a case report focussing on clinical and imaging description. RESULTS: Slit-lamp biomicroscopy revealed patent laser peripheral iridotomies OU. The anterior chamber was relatively deep in the center but 360 degrees narrow at the periphery, associated with an abnormally elevated iris contour OU. On dark-room gonioscopy, the angles were occludable with few areas of peripheral anterior synechiae. Anterior segment-adapted spectral domain-optical coherence tomography revealed an unusual iris profile. Despite a flat contour and normal thickness until the mid-periphery, the iris assumed a rectangular cross sectional shape (resembling a cobblestone) with an abnormal increase in its thickness in the periphery (360 degrees OU). Ultrasound biomicroscopy imaging showed a normal ciliary sulcus and ciliary body configuration, revealing no cysts at 360 degrees. Definitive relief of appositional angle closure was achieved with laser peripheral iridoplasty OU. CONCLUSIONS: This unusual anatomic condition of the peripheral iris, which has different characteristics when compared with ordinary cases of thick peripheral iris roll, may lead to angle closure and intraocular pressure elevation despite a patent iridotomy. Clinicians should be aware of this anatomic condition whenever dealing with cases of angle closure. PMID- 24240886 TI - A Novel Schlemm's Canal Scaffold: Histologic Observations. AB - PURPOSE: To assess the biocompatibility of a novel implant made of Nitinol (nickel-titanium alloy), designed to improve aqueous humor outflow. MATERIALS AND METHODS: In the first arm of biocompatibility testing, microstents were surgically inserted into Schlemm's canal (SC) of 2 non-human primates (NHPs), and a third NHP served as a surgical sham control. After 13 weeks the animals were killed, and the eyes were examined by light and scanning electron microscopy. Two masked investigators evaluated the histology sections. The second arm utilized 8 New Zealand white rabbits; each rabbit received a microstent inserted into the sclera and subconjunctival space by means of passage across the anterior chamber thus providing contact with several representative ocular tissues. The fellow eye of each rabbit underwent a sham procedure without microstent insertion. The rabbits were killed after 26 weeks, and a trained ocular pathologist examined the specimens using light microscopy. RESULTS: Histologic and scanning electron microscopy analysis of the NHPs demonstrated that the microstents were located in SC. There was no evidence of an acute or chronic inflammatory response, granulation response, or fibrosis in the outflow system or in adjacent tissues. Rabbit eyes showed minimal mononuclear cell infiltration and minimal fibrotic responses at the site of the implants when compared with sham-treated control eyes. CONCLUSIONS: The Hydrus Microstent was associated with minimal inflammation in both NHP and rabbit eyes with extended follow-up. These preclinical studies demonstrate that the Hydrus Microstent appears to have excellent long-term biocompatibility. PMID- 24240887 TI - Comparison of intraocular pressure measurements with the Reichert Pt100, the Keeler Pulsair Intellipuff portable noncontact tonometers, and Goldmann applanation tonometry. AB - PURPOSE: The aim of this study was to compare intraocular pressure (IOP) measurements using 2 portable tonometers, the Keeler Pulsair Intellipuff and the Reichert PT100, with Goldmann applanation tonometry (GAT). MATERIALS AND METHODS: Prospective cross-sectional study was conducted on normotensive and hypertensive patients recruited from the outpatient clinic of the University Hospital of Grenoble. IOP was measured using 2 portable noncontact tonometers (NCTs) and GAT in one eye of each patient in a random order. Central corneal thickness was measured with the Accutome PachPen Pachymeter. The Wilcoxon and t tests were used to compare the differences between tonometers, the Pearson and the Spearman correlation tests to evaluate the correlation among the methods, and the Bland Altman plots to evaluate the agreement among the methods. Intraclass correlation coefficient (ICC) was used to evaluate the agreement among the methods in normotensive and hypertensive patients separately. RESULTS: A total of 137 eyes of 137 patients were included, 104 normotensive and 33 hypertensive eyes. We found an excellent agreement between PT100 and GAT (ICC=0.77) and between Intellipuff and GAT (ICC=0.75) in normotensive patients. We found a fair to good agreement (ICC=0.67) between PT100 and GAT in hypertensive patients. The agreement we found between Intellipuff and GAT was also excellent in hypertensive patients (ICC=0.86). Both NCTs significantly overestimated IOP measurements compared with GAT in normotensive and hypertensive eyes (mean of the differences between PT100 and GAT: 1.3+/-2.1 and 8.1+/-4.6 mm Hg in normotensive and in hypertensive patients, respectively (P<0.05), and between Pulsair Intellipuff and GAT: 1.5+/-1.8 and 2.3+/-4.8 mm Hg in normotensive and in hypertensive patients, respectively (P<0.05). CONCLUSIONS: The 2 NCTs agree well with GAT in normotensive patients. The Pulsair Intellipuff also agrees well with GAT in hypertensive patients. PMID- 24240888 TI - Optical properties of manually and CAD/CAM-fabricated polymers. AB - The aim of this study was to compare the light translucency and fluorescence 5 manually and 11 CAD/CAM polymer materials to a glass-ceramic material. Light transmission was measured using a spectrophotometer. Overall light transmission (n=40) was calculated as the integration (tc (lambda) dlambda [10(-5)]) of all tc values for the wavelengths from 400 to 700 nm. One-Way-ANOVA, (Scheffe's post hoc) revealed following light transmission values: Artbloc Temp (33.1%; A), Polycon ae (33.6%; A), Cercon base PMMA (38.3%; B), Luxatemp Fluorescence (40.7%; C), Protemp 4 (41.6%; C), Structur 2 SC (43.1%; D), CAD Temp (45.0%; E), Paradigm MZ 100 (45.4%; E), New Outline (45.6%,E), Ambarino High-Class (45.9%; E, F), Fixtemp C&B (46.1%; E, F, G), Lava Ultimate (47.1%; F, G), Telio-CAD (47.3%; G), glass-ceramic Vita Mark II (50.8%; H), New Outline CAD (52.1%; H, I), QUATTRO DISC Eco PMMA (53.0%; I) and Zenotec PMMA (54.5%, J). Polymers from conventional and industrial polymerization show widely varying translucent and fluorescent properties when compared with glass-ceramics of the same color. PMID- 24240889 TI - The effects of incorporation of silver-zeolite on selected properties of mineral trioxide aggregate. AB - The purpose of this study was to evaluate some physical and chemical properties of MTA incorporated with antibacterial silver zeolite (SZ). 0%, 0.2% or 2% mass fraction of SZ was added to MTA powder. The amounts of calcium released from the specimen in deionized water were measured with an atomic absorption spectrophotometer. The setting times of the samples were evaluated using Gilmore type needles. For solubility and water absorption tests, the samples were placed in a cylindrical polystyrene-sealed container. At 7 days, the samples were removed from solutions and blotted dry for solubility and water absorption test. The highest calcium release was detected in 2% SZ MTA at 24 h. The addition of 2% SZ to MTA reduced the setting time statistically (p<0.05). 2% SZ MTA was significantly more soluble than MTA and 0.2 % SZ MTA (p<0.05). Further research is needed prior to clinical use of MTA with incorporated SZ. PMID- 24240890 TI - A comparison of the micro-shear bond strength and failure mode of non-enclosed and mold-enclosed luting cements bonded to metal. AB - The objective of the study was to compare 1) the mean micro-shear bond strength and 2) failure mode of cements to metals in nonenclosed and mold-enclosed specimens. Specimens were prepared in mold-enclosed and non-enclosed formats from two RMGIC's and a self-adhesive resin-cement. 3-way ANOVA analysis and Tukey post hoc tests were used to compare mean uSBS results (alpha=0.05). Failure mode was analysed with Pearson's chi-square test (alpha=0.05). uSBS was significantly affected by the factors substrate and method (p<0.001) but not by material (p=0.077). There was an interaction between substrate, method and material F (2,144)=3.57, p=0.031, and method and material (2,144)=5.86, p=0.004. All mold enclosed specimens for the three cements bonded to titanium and non-precious metal exhibited higher (p<0.001) mean uSBS than the non-enclosed specimens. Within this study, mold-enclosed specimens exhibited significantly higher (p<0.001) mean uSBS and adhesive failure compared to non-enclosed specimens. PMID- 24240891 TI - Evaluating a novel fissure caries model using swept source optical coherence tomography. AB - The objective of this study was to determine the efficacy of Swept Source Optical Coherence Tomography (SS-OCT) imaging in assessing a novel fissure caries model. Samples were imaged by both near infrared based SS-OCT and high resolution x-ray tomography imaging to non-destructively quantify artificial lesions. The mean relative reflectivities of the demineralized fissures were at least 6 times higher than the corresponding sound fissures (p<0.02). Importantly, this study demonstrated that SS-OCT reflectivity images can be used to predict the depth of fissure demineralization. Despite correctly evaluating the depth, this work showed that the lesion width calculated from SS-OCT reflectivity images did not accurately predict the demineralized width. The relative reflectivity could not accurately determine the mineral density of the demineralized lesions. SS-OCT detected subsurface fissure demineralization and could be used to determine if the decay process was advancing toward the enamel-dentin junction. PMID- 24240892 TI - Comparative study between laser sintering and casting for retention of resin composite veneers to cobalt-chromium alloy. AB - The purpose of this study was to evaluate and compare the bond strengths between resin composite veneer and laser-sintered cobalt-chromium (Co-Cr) alloy with and without retention devices (Laser-R and Laser-N respectively). Cast Co-Cr alloy with and without retention devices (Cast-R and Cast-N respectively) were also prepared for fabrication technique comparison. Disk-shaped Co-Cr alloy specimens were air-abraded with alumina and veneered with a veneering system, Estenia C&B (ES) or Ceramage (CE). After 20,000 thermocycles, tensile testing was performed. Data were analyzed by ANOVA and multiple comparison test. When no retention devices were present, no significant differences were observed between Laser-N/ES and Cast-N/ES, or between Laser- N/CE and Cast-N/CE, but ES exhibited significantly higher bond strength than CE. With retention devices, Laser-R/ES, Cast- R/ES and Laser-R/CE showed no significant differences, and their retention strengths were significantly higher than that of Cast- R/CE. Compared to cast Co Cr alloy, laser-sintered Co-Cr alloy with retention devices provided better retention durability for resin composite-veneered prostheses. PMID- 24240893 TI - Effects of a dental adhesive on cell cycle regulatory proteins. AB - Dental bonding agents may affect the cell cycle patterns and induce cell cycle arrest by blocking its progression. This study tested the cell cycle effects through cyclin-dependent kinase (cdc2) and Rb phosphorylation. Human lung fibroblasts (MRC5) were used for the experiments. The bonding agent tested was the total-etch XP bond. Extracts of the bonding agent were prepared and serial dilutions were tested. The effects of the bonding agent on cell survival, proliferation and DNA synthesis were tested by the SRB and BrdU assays. Analysis of cell cycle distribution was performed by flow cytometry. XP bond exhibited strong inhibition of DNA synthesis and after 48 h of exposure cells were accumulated in the G2/M phase. Cells exposed to the half maximal cell growth inhibitory concentration (IC50) showed an increase in cdc2 kinase and Rb phosphorylation. The results most likely indicate mutagenic effect of the tested agent. PMID- 24240894 TI - Polymerization behavior within adhesive layer of one- and two-step self-etch adhesives: a micro-Raman spectroscopic study. AB - This study investigated the polymerization behavior within the adhesive layer of one- and two-step self-etch adhesives at the dentincomposite interface. Dentin surfaces were applied with Clearfil S(3) Bond (TS), Clearfil S(3) Bond Plus (TSP) and Clearfil SE Bond (SE), and then placed with a light-curing resin composite. After water storage for 24 h, the bonded teeth were sectioned and polished perpendicular to the adhesive interface, and the degree of conversion (DC) of the adhesive layer between the dentin and composite were determined using micro-Raman analysis. For all the adhesives, the DCs of the adhesive layers significantly decreased near the adhesive-composite join (p<0.05). For the maximum DC value (Pmax) and the DC value at the adhesive-composite join (Pitf), TS was significantly lower than TSP and SE (p<0.05). The polymerization of oxygen inhibited layer at the top of the adhesive could not reach maximum DC even after polymerization of the overlying resin composite. PMID- 24240895 TI - Dynamic stress relaxation of orthodontic thermoplastic materials in a simulated oral environment. AB - Mechanical properties are crucial for screening orthodontic thermoplastic materials for invisible aligners. However, most of previous studies were carried out within laboratory conditions which limit our understanding of the mechanical behaviors of aligners within oral environment. In this study, we studied the dynamic stress relaxation of thermoplastic materials by combination of Bose ElectroForce and a homemade temperature-controlled water bath. The 3-h stress relaxation curves of five orthodontic thermoplastic materials were measured within 37 degrees C water bath as well as comparatively in ambient atmospheric environment (~20 degrees C). The percentage residual stress at 0, 30, 60, 90, 120, 150, and 180 min was selected for statistical analyses. As expected, the experimental results showed that the residual stress within all five materials decreased with time, and that this process was significantly accelerated in the 37 degrees C water bath (p<0.05). Compared with other materials, Erkodur and Masel exhibited slower relaxing rates in the 37 degrees C water bath (p<0.05). PMID- 24240896 TI - Influence of cementation and cement type on the fracture load testing methodology of anterior crowns made of different materials. AB - To evaluate the influence of cementation on fracture load of anterior crowns made of CAD/CAM-resin-blocks (ART), leucite-reinforced glass-ceramics (LRG), lithium disilicate ceramics (LIT), veneered zirconia (ZRO) and veneered alloy (DEG). Each crown group (n=15/subgroup) was cemented on the metal abutment as follows: i. using glass ionomer, ii. using self-adhesive resin cement, and iii. not cemented. Crowns were tested and analyzed with 2-way and 1-way ANOVA (Scheffe test), and Weibull statistics (p<0.05). Within LRG, self-adhesive cemented subgroup showed higher fracture load compared to other groups (p<0.001). Among DEG, lower results were measured for non-cemented crowns than for cemented (p<0.001). For ART, LIT and ZRO no influence of cementation was observed. For fracture load test methodology, metal ceramic crowns should be generally cemented. Glass-ceramic crowns should be cemented using adhesive cement. Cementation and cement type did not have an influence on the fracture load results for resin, zirconia or lithium disilicate crowns. PMID- 24240897 TI - Influence of proximal contacts and FRC posts on the fracture behavior of premolars with class II composite restorations: an in-vitro study. AB - The purpose of this study was to evaluate the influence of the number of proximal contacts and fiber-reinforced composite (FRC) post insertion on the fracture behavior of endodontically treated premolars with class II (MOD) cavities and direct composite restorations. Forty-eight single-rooted human premolars were endodontically treated and prepared with standardized MOD (mesio-occluso-distal) cavities. One-half of the teeth additionally received FRC-posts (DT Light SL) luted with Panavia F resin cement. All of the specimens were restored with direct composite restorations, and the teeth were embedded in proximal contact with either zero, one or two adjacent tooth-replicas. Eight sound premolars served as control. After thermomechanical ageing, the samples were loaded until fracture at an angle of 30 degrees . The sound teeth showed the highest mean fracture load. Teeth with one or two proximal contacts and FRC-posts showed only statistically insignificantly lower values. All of the other groups had significantly lower values. PMID- 24240898 TI - Magnetic fields from electric toothbrushes promote corrosion in orthodontic stainless steel appliances but not in titanium appliances. AB - Electric toothbrushes are widely used, and their electric motors have been reported to produce low-frequency electromagnetic fields that induced electric currents in metallic objects worn by the users. In this study, we showed that electric toothbrushes generated low-frequency magnetic fields (MFs) and induced electric currents in orthodontic appliances in artificial saliva (AS), which accelerated corrosion in stainless steel (SUS) appliances, but not in titanium (Ti) appliances; the corrosion was evaluated by using an inductively coupled plasma-optical emission spectrometer and a three-dimensional laser confocal microscope. The pH of AS used for appliance immersion did not change during or after MF exposure. These results suggested that MF-induced currents from electric toothbrushes could erode SUS appliances, but not Ti appliances, because of their high corrosion potentials. Further studies are required to clarify the mechanisms of metallic corrosion by induced currents in dental fields, which may trigger metal allergies in patients. PMID- 24240899 TI - In vitro short-term bonding performance of zirconia treated with hot acid etching and primer conditioning etching and primer conditioning. AB - This study aimed to investigate and compare the resin bond strengths of zirconia conditioned as follows: alumina sandblasting; alumina sandblasting+application of 10-MDP-containing primer; alumina sandblasting+application of Z-Prime Plus or Metal/Zirconia Primer (new zirconia primers); tribochemical silica coating+silanization; hot acid etching in three different combinations [H2SO4/(NH4)2SO4, HF/HNO3, H2SO4/HF/HNO3]+application of 10-MDP-containing primer. Shear bond strengths (SBS) after water storage for 24 h and 40 days were measured to assess resin bonding performance. Surface and chemical properties of conditioned zirconia surfaces and primers were characterized using scanning electron microscopy, energy dispersive X-ray spectrometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Surface roughness ranked in descending order was: hot acid etching > tribochemical silica coating > alumina sandblasting. Combination of tribochemical silica coating and silanization showed the highest initial SBS (12.46+/-2.13 MPa) (P<0.01). Etching with H2SO4/(NH4)2SO4 (13.15+/-3.24 MPa) and HF/HNO3 (13.48+/-2.15 MPa) showed significantly better bond durability (P<0.01). Hot acid etching seemed to be a promising surface roughening treatment to improve resin-zirconia bonding. PMID- 24240900 TI - The effects of glass ionomer and flowable composite liners on the fracture resistance of open-sandwich class II restorations. AB - This in vitro study aimed to investigate the effects of glass-ionomer and flowable composite liners on the fracture resistance of Class II amalgam and composite restorations. Group 1 cavities were restored with amalgam and Group 4 cavities with nanofill composite after the application of a dentin-bonding agent. For the remaining groups, light-cured-glass-ionomer liner was used in a gingival floor proximal box (Groups 2, 5) or flowable composite was used as a liner (Groups 3, 6), the remainder of the cavity was restored with amalgam (Groups 2, 3) or composite (Groups 5, 6). The restorations were loaded in compression to failure. The data was analyzed using Tukey's multiple comparison test. The fracture resistance was significantly higher (p<0.05) in Group 3 than in all other groups, except Group 2 (p>0.05). Flowable composite, glass-ionomer liners increased the fracture resistance of open-sandwich Class II amalgam restorations. PMID- 24240901 TI - Analysis of residual stress in the resin of metal-resin adhesion structures by scanning acoustic microscopy. AB - The residual stress caused by polymerization shrinkage and thermal contraction of a heat-curing resin containing 4-META on a metal-resin structure was measured by a scanning acoustic microscope. The tensile residual stress in the resin occurred within 70 um of the adhesion interface with a flat plate specimen. The maximum tensile stress was about 58 MPa at the interface. On a metal plate specimen with retention holes, ring-like cracks in the resin occurred around the retention holes with the adhesive specimen and many linear cracks occurred in the resin vertical to the longitudinal direction of the metal frame with the non-adhesive specimens. There was tensile residual stress on the resin surface at the center of the retention holes of the adhesion specimen, indicating that the stress in the specimen with surface treatment for adhesion was higher than in that without surface treatment. PMID- 24240902 TI - Mechanical properties of experimental silicone soft lining materials. AB - The purpose of this study was to evaluate the mechanical properties of experimental silicone elastomers, Silastic((r)) MDX 4-4210 reinforced with silica fillers, to assess its potential as a denture soft lining material. The mechanical properties measured included tensile strength, percentage elongation, tear strength, and Shore A hardness. Using one-way ANOVA and Tukey's HSD test, the results indicated that silicone elastomers with filler loadings of 6, 8, and 10 phr had significantly greater tensile strength, percentage elongation, tear strength with a softer surface compared with commercial materials (p<0.001). In conclusion, the experimental silicone elastomers revealed acceptable mechanical properties to be used as denture soft lining materials. PMID- 24240903 TI - The possibility of genistein as a new direct pulp capping agent. AB - Genistein, kind of soy isoflavones, is well-known as natural ingredients and consumed as health foods and supplements. They are expected to improve renal function. They have high-affinity to estrogen receptor beta expressed predominantly in bone tissue, they prevent osteoporosis specifically and safely. We examined whether genistein can be a new direct capping agent. In this study, we examined the effect of genistein for the proliferation and differentiation of rat dental pulp cells in vitro and the ability of tertiary dentin formation in vivo. As a result, rat dental pulp cells with genistein were increased activity of ALPase and showed alizarin red positive-staining. Calcification-related genes expression has been confirmed by the addition of genistein. From in vivo study, high quality of tertiary dentin formation and minor pulp reaction were observed. From these findings, it was suggested that genistein may be useful agent for direct pulp capping. PMID- 24240904 TI - Effects of calcium hydroxide and propolis intracanal medicaments on bond strength of resin-based endodontic sealer as assessed by push-out test. AB - The aim of this study was to investigate the effects of calcium hydroxide (Ca(OH)2) and propolis intracanal medicaments on bond strength of AH Plus to root dentin. After chemomechanical instrumentation using Revo-S rotary system, three groups of root canal specimens were prepared: 10 root canals were left untreated as controls (G1), 10 received Ca(OH)2 intracanal medicament (G2), and another 10 received propolis intracanal medicament (G3). Canals were obturated with AH Plus and gutta-percha. After bond strength evaluation using micro push-out test, data were analyzed using ANOVA and Tamhane's test (p=0.05). At coronal and middle thirds, there were no significant differences in bond strength among the three groups (p>0.05). At apical third, G3 was significantly superior to G2 (p<0.05) and G1 (p<0.05), but there was no significant difference between G2 and G1 (p>0.05). Therefore, when AH Plus was used as the sealer in endodontic treatments, its combined use with propolis as an intracanal medicament seemed to result in favorable sealer-dentin interfacial bond strength. PMID- 24240905 TI - Efficacy of self-adjusting file and passive ultrasonic irrigation on removing calcium hydroxide from root canals. AB - The aim of this study was to evaluate the efficiencies of the self-adjusting file (SAF) system, passive ultrasonic irrigation (PUI), and conventional irrigation (CI) in removing calcium hydroxide (CH) from root canals. Fifty-one mandibular premolars were used. After root canals were instrumented and filled with a CH paste, 45 teeth were randomly assigned to three experimental groups according to CH removal technique: SAF system, PUI, or CI. The remaining 6 teeth served as positive and negative controls. All samples were evaluated by scanning electron microscopy (SEM) and scored. None of the techniques removed CH completely. However, results at coronal, middle and apical thirds showed that PUI technique was significantly more effective than SAF and CI in removing CH dressing residues from root canal walls. PMID- 24240906 TI - Adsorption study of pellicle proteins to gold, silica and titanium by quartz crystal microbalance method. AB - Initial stage of biofilm formation is the adhesion of salivary pellicle proteins on the material surfaces. The aim of the present study was to evaluate the adsorption behaviors of saliva pellicle proteins onto a gold, silica and titanium by using the 27 MHz quartz crystal microbalance method. As pellicle proteins, lactoferrin, lysozyme, defensin and mucin were evaluated. Adsorption amount of lactoferrin to silica was significantly lower than gold and titanium. Significant differences were detected between titanium and silica for the adsorption amounts of lysozyme. Chemical bond formation of sulfur atom of lysozyme and gold could be suggested. There were no significant differences of the adsorption amount of beta defensin among each substrate. For mucin adsorption, gold showed the highest adsorption amount. It is presumed that electrostatic repulsion caused less adsorption amounts of mucin to titanium and silica. In conclusion, the differences of the adsorption behaviors of pellicle proteins could be clearly identified. PMID- 24240907 TI - Acceleration of curing of resin composite at the bottom surface using slow-start curing methods. AB - The aim of this study was to evaluate the effect of two slow-start curing methods on acceleration of the curing of resin composite specimens at the bottom surface. The light-cured resin composite was polymerized using one of three curing techniques: (1) 600 mW/cm(2) for 60 s, (2) 270 mW/cm(2) for 10 s+0-s interval+600 mW/cm(2) for 50 s, and (3) 270 mW/cm(2) for 10 s+5-s interval+600 mW/cm(2) for 50 s. After light curing, Knoop hardness number was measured at the top and bottom surfaces of the resin specimens. The slow-start curing method with the 5-s interval caused greater acceleration of curing of the resin composite at the bottom surface of the specimens than the slow-start curing method with the 0-s interval. The light-cured resin composite, which had increased contrast ratios during polymerization, showed acceleration of curing at the bottom surface. PMID- 24240908 TI - Contamination of dental zirconia before final firing: effects on mechanical properties. AB - Plate-like specimens were prepared, using a diamond saw, from Cercon -a pre sintered yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) block. These specimens were treated with 10 kinds of dental materials which acted as contaminants, and then sintered at 1,350 degrees C or 1,450 degrees C. After the final firing, specimens were subjected to a three-point flexural test and Vickers hardness test. Their surfaces were also characterized by scanning electron microscopy and X-ray diffractometry. Phosphorus-containing contaminants reduced the three-point flexural strength and hardness of final sintered zirconia due to the formation of YPO4 and phase transformation from tetragonal to monoclinic zirconia. Gypsum also reduced both mechanical properties due to the formation of CaZrO3 and phase transformation from tetragonal to cubic zirconia. Other contaminants showed no adverse effects on the mechanical properties of final sintered zirconia. PMID- 24240911 TI - Ice (2): Gerhard Richter. PMID- 24240912 TI - Study: Exercise may match medication in reducing mortality associated with cardiovascular disease, diabetes. PMID- 24240913 TI - 2013 Nobel Prize recognizes work of scientists who illuminated molecular transport system of cells. PMID- 24240914 TI - Costs of cardiac care likely to increase, despite advances in prevention, care. PMID- 24240924 TI - The challenge of treating heart failure: a diverse disease affecting diverse populations. PMID- 24240925 TI - Need for increased awareness and evidence-based therapies for patients hospitalized for heart failure. PMID- 24240926 TI - Embedding cardiovascular research into practice. PMID- 24240927 TI - Patient-specific stem cells and cardiovascular drug discovery. PMID- 24240928 TI - A piece of my mind. Learning from improbable longevity. PMID- 24240929 TI - What's new with measuring cholesterol? PMID- 24240930 TI - Improving outlook for elderly patients with aortic stenosis. PMID- 24240931 TI - The cardiovascular disease researcher. PMID- 24240932 TI - Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. AB - IMPORTANCE: Obesity is a risk factor for atrial fibrillation. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known. OBJECTIVE: To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure. DESIGN, SETTING, AND PATIENTS: Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up. INTERVENTIONS: Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors. MAIN OUTCOMES AND MEASURES: The primary outcomes were Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity. Scores were measured every 3 months from baseline to 15 months. Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter, echocardiographic left atrial area, and interventricular septal thickness. RESULTS: Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P < .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P < .001), symptom severity scores (8.4 and 1.7 points, P < .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02). CONCLUSIONS AND RELEVANCE: In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000497000. PMID- 24240933 TI - Comparison of a novel method vs the Friedewald equation for estimating low density lipoprotein cholesterol levels from the standard lipid profile. AB - IMPORTANCE: In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels. OBJECTIVE: To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio. DESIGN, SETTING, AND PARTICIPANTS: We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets. MAIN OUTCOMES AND MEASURES: Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD). RESULTS: In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6% 91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison). CONCLUSIONS AND RELEVANCE: A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01698489. PMID- 24240934 TI - Outcomes following transcatheter aortic valve replacement in the United States. AB - IMPORTANCE: Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for the treatment of severe, symptomatic aortic stenosis and inoperable status (in 2011) and high-risk but operable status (starting in 2012). A national registry (the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy [STS/ACC TVT] Registry) was initiated to meet a condition for Medicare coverage and also facilitates outcome assessment and comparison with other trials and international registries. OBJECTIVE: To report the initial US commercial experience with TAVR. DESIGN, SETTING, AND PARTICIPANTS: We obtained results from all eligible US TAVR cases (n=7710) from 224 participating registry hospitals following the Edwards Sapien XT device commercialization (November 2011-May 2013). MAIN OUTCOMES AND MEASURES: Primary outcomes included all-cause in-hospital mortality and stroke following TAVR. Secondary analyses included procedural complications and outcomes by clinical indication and access site. Device implantation success was defined as successful vascular access, deployment of a single device in the proper anatomic position, appropriate valve function without either moderate or severe AR, and successful retrieval of the delivery system. Thirty-day outcomes are presented for a representative 3133 cases (40.6%) at 114 centers with at least 80% complete follow-up reporting. RESULTS: The 7710 patients who underwent TAVR included 1559 (20%) cases that were inoperable and 6151 (80%) cases that were high-risk but operable. The median age was 84 years (interquartile range [IQR], 78-88 years); 3783 patients (49%) were women and the median STS predicted risk of mortality was 7% (IQR, 5%-11%). At baseline, 2176 patients (75%) were either not at all satisfied (1297 patients [45%]) or mostly dissatisfied (879 patients [30%]) with their symptom status; 2198 (72%) had a 5-m walk time longer than 6 seconds (slow gait speed). The most common vascular access approach was transfemoral (4972 patients [64%]), followed by transapical (2197 patients [29%]) and other alternative approaches (536 patients [7%]); successful device implantation occurred in 7069 patients (92%; 95% CI, 91%-92%). The observed incidence of in-hospital mortality was 5.5% (95% CI, 5.0%-6.1%). Other major complications included stroke (2.0%; 95% CI, 1.7%-2.4%), dialysis-dependent renal failure (1.9%; 95% CI, 1.6%-2.2%), and major vascular injury (6.4%; 95% CI, 5.8% 6.9%). Median hospital stay was 6 days (IQR, 4-10 days), with 4613 (63%) discharged home. Among patients with available follow-up at 30 days (n=3133), the incidence of mortality was 7.6% (95% CI, 6.7%-8.6%) (noncardiovascular cause, 52%); a stroke had occurred in 2.8% (95% CI, 2.3%-3.5%), new dialysis in 2.5% (95% CI, 2.0%-3.1%), and reintervention in 0.5% (95% CI, 0.3%-0.8%). CONCLUSIONS AND RELEVANCE: Among patients undergoing TAVR at US centers in the STS/ACC TVT Registry, device implantation success was achieved in 92% of cases, the overall in-hospital mortality rate was 5.5%, and the stroke rate was 2.0%. Although these postmarket US approval findings are comparable with prior published trial data and international experience, long-term follow-up is essential to assess continued efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01737528. PMID- 24240936 TI - Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review. AB - IMPORTANCE: Ischemic heart disease is the leading cause of death globally. Coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) are the revascularization options for ischemic heart disease. However, the choice of the most appropriate revascularization modality is controversial in some patient subgroups. OBJECTIVE: To summarize the current evidence comparing the effectiveness of CABG surgery and PCI in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease (CAD), diabetes, or left ventricular dysfunction (LVD). EVIDENCE REVIEW: A search of OvidSP MEDLINE, EMBASE, and Cochrane databases between January 2007 and June 2013, limited to randomized clinical trials (RCTs) and meta-analysis of trials and/or observational studies comparing CABG surgery with PCI was performed. Bibliographies of relevant studies were also searched. Mortality and major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause mortality, myocardial infarction, stroke, and repeat revascularization) were reported wherever possible. FINDINGS: Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with ULMD, multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX <=22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies. CONCLUSIONS AND RELEVANCE: Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise. PMID- 24240935 TI - Trends in aortic valve replacement for elderly patients in the United States, 1999-2011. AB - IMPORTANCE: There is a need to describe contemporary outcomes of surgical aortic valve replacement (AVR) as the population ages and transcatheter options emerge. OBJECTIVE: To assess procedure rates and outcomes of surgical AVR over time. DESIGN, SETTING, AND PARTICIPANTS: A serial cross-sectional cohort study of 82,755,924 Medicare fee-for-service beneficiaries undergoing AVR in the United States between 1999 and 2011. MAIN OUTCOMES AND MEASURES: Procedure rates for surgical AVR alone and with coronary artery bypass graft (CABG) surgery, 30-day and 1-year mortality, and 30-day readmission rates. RESULTS: The AVR procedure rate increased by 19 (95% CI, 19-20) procedures per 100,000 person-years over the 12-year period (P<.001), with an age-, sex-, and race-adjusted rate increase of 1.6% (95% CI, 1.0%-1.8%) per year. Mortality decreased at 30 days (absolute decrease, 3.4%; 95% CI, 3.0%-3.8%; adjusted annual decrease, 4.1%; 95% CI, 3.7%- 4.4%) per year and at 1 year (absolute decrease, 2.6%; 95% CI, 2.1%-3.2%; adjusted annual decrease, 2.5%; 95% CI, 2.3%-2.8%). Thirty-day all-cause readmission also decreased by 1.1% (95% CI, 0.9%-1.3%) per year. Aortic valve replacement with CABG surgery decreased, women and black patients had lower procedure and higher mortality rates, and mechanical prosethetic implants decreased, but 23.9% of patients 85 years and older continued to receive a mechanical prosthesis in 2011. CONCLUSIONS AND RELEVANCE: Between 1999 and 2011, the rate of surgical AVR for elderly patients in the United States increased and outcomes improved substantially. Medicare data preclude the identification of the causes of the findings and the trends in procedure rates and outcomes cannot be causally linked. Nevertheless, the findings may be a useful benchmark for outcomes with surgical AVR for older patients eligible for surgery considering newer transcatheter treatments. PMID- 24240937 TI - Subgroup analyses in trial reports comparing percutaneous coronary intervention with coronary artery bypass surgery. PMID- 24240938 TI - Surgery vs watchful waiting for mitral regurgitation. PMID- 24240939 TI - Surgery vs watchful waiting for mitral regurgitation. PMID- 24240940 TI - Surgery vs watchful waiting for mitral regurgitation--reply. PMID- 24240941 TI - Autism in children born after in vitro fertilization. PMID- 24240942 TI - Breast cancer screening recommendations. PMID- 24240943 TI - Autism in children born after in vitro fertilization--reply. PMID- 24240945 TI - Breast cancer screening recommendations--reply. PMID- 24240947 TI - Disturbances of the heart: the resort treatment of chronic heart disease. PMID- 24240948 TI - JAMA patient page. Obesity and the heart. PMID- 24240949 TI - Accuracy of full-arch scans using intraoral scanners. AB - OBJECTIVES: This study aimed to evaluate the accuracy of intraoral scanners in full-arch scans. MATERIALS AND METHODS: A representative model with 14 prepared abutments was digitized using an industrial scanner (reference scanner) as well as four intraoral scanners (iTero, CEREC AC Bluecam, Lava C.O.S., and Zfx IntraScan). Datasets obtained from different scans were loaded into 3D evaluation software, superimposed, and compared for accuracy. One-way analysis of variance (ANOVA) was implemented to compute differences within groups (precision) as well as comparisons with the reference scan (trueness). A level of statistical significance of p < 0.05 was set. RESULTS: Mean trueness values ranged from 38 to 332.9 MUm. Data analysis yielded statistically significant differences between CEREC AC Bluecam and other scanners as well as between Zfx IntraScan and Lava C.O.S. Mean precision values ranged from 37.9 to 99.1 MUm. Statistically significant differences were found between CEREC AC Bluecam and Lava C.O.S., CEREC AC Bluecam and iTero, Zfx Intra Scan and Lava C.O.S., and Zfx Intra Scan and iTero (p < 0.05). CONCLUSIONS: Except for one intraoral scanner system, all tested systems showed a comparable level of accuracy for full-arch scans of prepared teeth. Further studies are needed to validate the accuracy of these scanners under clinical conditions. CLINICAL RELEVANCE: Despite excellent accuracy in single-unit scans having been demonstrated, little is known about the accuracy of intraoral scanners in simultaneous scans of multiple abutments. Although most of the tested scanners showed comparable values, the results suggest that the inaccuracies of the obtained datasets may contribute to inaccuracies in the final restorations. PMID- 24240950 TI - Very early postnatal changes in splanchnic circulation in term infants. AB - BACKGROUND: Reversed blood flow has been reported in the superior mesenteric artery (SMA) in 92% of healthy term newborns at 2 h of age. By 24 h after birth the end-diastolic velocity became positive in all of the infants. OBJECTIVE: To characterize hemodynamic changes in the coeliac artery and superior mesenteric artery in healthy term newborns during the first 6 h after birth and to specify the time interval when the negative values of end-diastolic velocity in the superior mesenteric artery become positive. MATERIALS AND METHODS: Our study included 30 healthy term newborns. The blood flow velocity was assessed by Doppler ultrasonography at 2 h, 4 h and 6 h after birth. RESULTS: The end diastolic velocity in the superior mesenteric artery changed from negative values at the age of 2 h (-0.9 cm/s, range -13.2 to 0.0) to positive (7.08 cm/s, range 6.3 to 13.5, P < 0.001) at 6 h after birth. In the coeliac artery, the end diastolic velocity increased during this period, but negative values were not observed (11.8 cm/s, range 9.3 to 13.9 at 2 h and 18.03 cm/s, range 14.2 to 27.6 at 6 h). CONCLUSION: Important changes occur in splanchnic circulation during the first 6 h after birth. The rise in end-diastolic velocity in the superior mesenteric artery from negative to positive values in 83% of healthy term newborns is the most important change. PMID- 24240951 TI - Structure and function of the microtubular cytoskeleton during pollen development in Gasteria verrucosa (Mill.) H. Duval. AB - In a study of pollen development in Gasteria verrucosa, the changes in the spatial organization of microtubules were related to the processes of cell division, nuclear movement and cytomorphogenesis. Sections of polyethylene-glycol embedded anthers of G. verrucosa were processed immunocytochemically to record the structure and succession of fluorescently labeled microtubular configurations. Using microspectrophotometric measurements the relative quantity of tubulin in microtubules per unit of cytoplasm was determined. Cell dimensions and nuclear positions were measured to relate changes in cell shape and nuclear movements to microtubular configurations. Microtubules were detected in the different cells during microsporogenesis and microgametogenesis. In microspore mother cells which are approximately isodiametric at interphase, microtubules were predominantly arranged in a criss-cross pattern. The microtubules probably function as a flexible cytoskeleton which sustains the integrity of the cytoplasm. Bundles of microtubules were observed in the microspores, in the generative cells and during nuclear division, where they functioned in establishing and maintaining cell and spindle shapes. Microtubules radiating from nuclear membranes appeared to fix the nucleus in position. In prophase of meiosis and after microspore mitosis, periods a high fluorescence intensity were distinguished indicating a variation in the quantity of microtubules. PMID- 24240952 TI - Chlorophyll biosynthesis from glutamate or 5-aminolevulinate in intact Euglena chloroplasts. AB - Chloroplasts observed, by electron microscopy, to be intact and uncontaminated, with high rates of light-dependent protein synthesis and CO2 fixation were isolated from cells grown on low-vitamin-B12 medium in the light or from cells grown in the same medium in the dark and then exposed to light for 36 h. Both types of chloroplasts were active but less variability was encountered with developing chloroplasts from 36-h cells. The 36-h chloroplasts showed good light dependent incorporation of 5-amino-levulinic acid (ALA) or L-glutamic acid into chlorophyll (Chl) a which was linear for approx. 1 h. The specific activity of the Chl a remained the same after conversion to pheophytin a, methylpheophorbide a or pyromethylpheophorbide a and rechromatography, indicating that the label was in the tetrapyrrole. Incorporation of ALA was inhibited by levulinic acid, and by chloramphenicol and other inhibitors of translation of 70S-type chloroplast ribosomes at concentrations which did not appreciably inhibit photosynthesis but which blocked plastid protein synthesis nearly completely. Cycloheximide, an inhibitor of translation on 87S cytoplasmic ribosomes of Euglena, was without effect. The 70S inhibitors did not block uptake of labeled ALA. Although labeled glycine was taken up by the plastids, no incorporation into Chl a was observed. Thus the developing chloroplasts appear to contain all of the enzymatic machinery necessary to convert glutamic acid to Chl via the C5 pathway of ALA formation but the Shemin pathway from succinyl coenzyme A and glycine to ALA appears to be absent. The requirement for plastid protein synthesis concomitant with Chl synthesis indicates a regulatory interaction and also indicates that at least one protein influencing Chl synthesis is synthesized on 70S-type plastid ribosomes and is subject to metabolic turnover. PMID- 24240953 TI - Concanavalin A is synthesized as a glycoprotein precursor. AB - Concanavalin A (Con A) is a tetrameric lectin which is synthesized in the cotyledons of developing jack-bean (Canavalia ensiformis (L.) D.C.) seeds and accumulates in the protein bodies of storage-parenchyma cells. The polypeptides of Con A have a molecular weight of 27000 and a relative molecular mass (Mr) of 30000 when analyzed by gel electrophoresis on denaturing polyacrylamide gels. In vitro translation of RNA isolated from immature jack-bean cotyledons shows that Con A is synthesized as a polypeptide with Mr 34000. In-vivo pulse labeling of cotyledons with radioactive amino acids or glucosamine also resulted in the formation of a 34000-Mr polypeptide. In-vivo labeling with radioactive amino acids in the presence of tunicamycin yielded an additional polypeptide of 32000 Mr. Together these results indicate that Con A is cotranslationally processed by the removal of a signal sequence and the addition of an oligosaccharide side chain of corresponding size. Analysis of the structure of the oligogosaccharide side chain was accomplished through glycosidase digestion of glycopeptides isolated from [(3)H]glucosamine-labeled Con A. Incubation of the labeled glycopeptides with endoglycosidase H, alpha-mannosidase or beta-N acetylglucosaminidase, followed by gel filtration, allowed us to deduce that the oligosaccharide side chain of pro-Con A is a high-mannose oligosaccharide. Pulse chase experiments with labeled amino acids are consistent with the interpretation that the glycosylated precursor of Con A is processed to mature Con A (Mr=30000). The 4000 decrease in Mr is interpreted to result from the removal of a small glycopeptide. The implications of the conversion of a glycoprotein pro-Con A to mature Con A are discussed in the context of the unique circular permutation of the primary structure of Con A. PMID- 24240954 TI - Phytochrome-mediated polarotropism of Adiantum capillus-veneris L. protonemata as analyzed by microbeam irradiation with polarized light. AB - Perception of polarized light inducing phytochrome-mediated polarotropism in protonemata of the fern Adiantum capillus-veneris L. was analyzed using brief microbeam irradiation with polarized red (R) or far-red light (FR). The polarotropic response inducible by irradiation of the subapical 10-30-MUm part with polarized R vibrating parallel to the cell axis was nullified by subsequently giving R at the apical 0-2.5-MUm region. This inhibitory effect of R showed an action dichroism, that is, polarized R vibrating normal to the cell axis was effective but the parallel-vibrating R was not. On the other hand, FR irradiation of the extreme tip after irradiation of the whole cell with depolarized R effectively induced a tropic response. This FR effect also showed action dichroism, with parallel-vibrating polarized FR being more effective than FR vibrating normal to the cell axis. When the apical-dome region and the adjacent subapical 10-20-MUm region were sequentially irradiated with polarized R vibrating obliquely in different directions, polarotropism took place depending on the vibrating direction of the light given to the apical-dome region. Obliquely vibrating polarized FR given to the apical dome after irradiation of the whole cell with depolarized R also induced polarotropism. Thus, the difference in amount (or percent) of the far-redabsorbing form of phytochrome (Pfr) between the extreme tip and the subapical region appears to be crucial in regulating the direction of apical growth; the difference in Pfr level between the two sides of the protonemal apex may occur mainly at the apical dome. Furthermore, the transition moments of the red-absorbing form of phytochrome (Pr) and Pfr seem to be aligned parallel and normal, respectively, to the cell surface at the periphery of the apical hemisphere. PMID- 24240955 TI - Phosphorylation of chloroplast membrane proteins partially protects against photoinhibition. AB - Thylakoids isolated from peas (Pisum sativum cv. Kelvedon Wonder) and phosphorylated by incubation with ATP have been compared with non-phosphorylated thylakoids in their sensitivity to photoinhibition by exposure to illumination in vitro. Assays of the kinetics of fluorescence induction at 20 degrees C and the fluorescence emission spectra at-196 degrees C indicate a proportionally larger decrease in fluorescence as a result of photoinhibitory treatment of non phosphorylated compared with phosphorylated thylakoids. It is concluded that protein phosphorylation can afford partial protection to thylakoids exposed to photoinhibitory conditions. PMID- 24240956 TI - Blue- and red-light action in photoorientation of chloroplasts in Adiantum protonemata. AB - An action spectrum for the low-fluencerate response of chloroplast movement in protonemata of the fern Adiantum capillus-veneris L. was determined using polarized light vibrating perpendicularly to the protonema axis. The spectrum had several peaks in the blue region around 450 nm and one in the red region at 680 nm, the blue peaks being higher than the red one. The red-light action was suppressed by nonpolarized far-red light given simultaneously or alternately, whereas the bluelight action was not. Chloroplast movement was also induced by a local irradiation with a narrow beam of monochromatic light. A beam of blue light at low energy fluence rates (7.3.10(-3)-1.0 W m(-2)) caused movement of the chloroplasts to the beam area (positive response), while one at high fluence rates (10 W m(-2) and higher) caused movement to outside of the beam area (negative response). A red beam caused a positive response at fluence rates up to 100 W m(-2), but a negative response at very high fluence rates (230 and 470 W m( 2)). When a far-red beam was combined with total background irradiation with red light at fluence rates causing a low-fluence-rate response in whole cells, chloroplasts moved out of the beam area. When blue light was used as background irradiation, however, a narrow far-red beam had no effect on chloroplast distribution. These results indicate that the light-oriented movement of Adiantum chloroplasts is caused by red and blue light, mediated by phytochrome and another, unidentified photoreceptor(s), respectively. This movement depends on a local gradient of the far-red-absorbing form of phytochrome or of a photoexcited blue-light photoreceptor, and it includes positive and negative responses for both red and blue light. PMID- 24240957 TI - Larger adenylate energy charge and ATP/ADP ratios in aerenchymatous roots of Zea mays in anaerobic media as a consequence of improved internal oxygen transport. AB - Internal transport of O2 from the aerial tissues along the adventitious roots of intact maize plants was estimated by measuring the concentrations of adenine nucleotides in various zones along the root under an oxygen-free atmosphere. Young maize plants were grown in nutrient solution under conditions that either stimulated or prevented the formation of a lysigenous aerenchyma, and the roots (up to 210 mm long) were then exposed to an anaerobic (oxygen-free) nutrient solution. Aerenchymatous roots showed higher values than non-aerenchymatous ones for ATP content, adenylate energy charge and ATP/ADP ratios. We conclude that the lysigenous cortical gas spaces help maintain a high respiration rate in the tissues along the root, and in the apical zone, by improving internal transport of oxygen over distances of at least 210 mm. This contrasted sharply with the low energy status (poor O2 transport) in non-aerenchymatous roots. PMID- 24240958 TI - Reactivity of glyoxylate with hydrogen perioxide and simulation of the glycolate pathway of C3 plants and Euglena. AB - The nonenzymatic reaction of glyoxylate and H2O2 was measured under physiological conditions of the pH and concentrations of reactants. The reaction of glyoxylate and H2O2 was secondorder, with a rate constant of 2.27 l mol(-1) s(-1) at pH 8.0 and 25 degrees C. The rate constant increased by 4.4 times in the presence of Zn(2+) and doubled at 35 degrees C. We propose a mechanism for the reaction between glyoxylate and H2O2. From a comparison of the rates of H2O2 decomposition by catalase and the reaction with glyoxylate, we conclude that H2O2 produced during glycolate oxidation in peroxisomes is decomposed by catalase but not by the reaction with glyoxylate, and that photorespiratory CO2 originates from glycine, but not from glyoxylate, in C3 plants. Simulation using the above rate constant and reported kinetic parameters leads to the same conclusion, and also makes it clear that alanine is a satisfactory amino donor in the conversion of glyoxylate to glycine. Some serine might be decomposed to give glycine and methylene-tetrahydrofolate; the latter is ultimately oxidized to CO2. In the simulation of the glycolate pathway of Euglena, the rate constant was high enough to ensure the decarboxylation of glyoxylate by H2O2 to produce photorespiratory CO2 during the glycolate metabolism of this organism. PMID- 24240959 TI - beta-D-glucan-hydrolase activities in pure cell-wall-enriched fractions from Valerianella olitoria cells. AB - An effective method for the preparation of purified cell walls from mesophyll cells of Valerianella olitoria has been developed. Cells were isolated by a mechanical procedure only and crude cell walls were prepared from cell homogenates. Crude wall suspensions were fractionated in a discontinuous sucrose gradient and the wall fragments recovered were examined by scanning electron microscopy. An evaluation of the degree of purity and physiological integrity of the wall fragments showed that the material found at the 50-60% (w/w) interface consisted mostly of wall particles of high purity. Some characteristics of the purified walls are reported, especially the following enzyme activities: beta-D glucosidase (EC 3.2.1.21) and the beta-D-glucanases, 1,4-beta-glucan glucanohydrolase (EC 3.2.1.4), 1,4-beta-glucan cellobiohydrolase (EC 3.2.1.91), 1,3-beta-glucan glucanohydrolase (EC 3.2.1.39), 1,3-beta-glucan glucohydrolase (EC 3.2.1.58). The results provided evidence for the microlocalization of some hydrolases and indicated that enzymes extracted only with a high-salt concentration buffer were confined to walls whereas the 2-amino-2-(hydroxymethyl) 1,3-propanediol (Tris)-solubilized enzymes could have multiple sites, e.g. walls and membranes of the endoplasmic reticulum. PMID- 24240960 TI - Influence of external factors on callose and cellulose synthesis during incubation in vitro of intact cotton fibres with [(14)C]sucrose. AB - Seed clusters, with adhering fibres, from individual locules of 36-d-old fruit capsules of Gossypium arboreum L. were fed with [(14)C]sucrose in vitro. The fibres synthesised, under standard conditions, (1->3)-beta-D-glucan (callose) and (1->4)-beta-D-glucan (cellulose) in the ratio of approx. 2:1. Under a great variety of different conditions this product ratio remained more or less constant, even when total glucan synthesis was strongly inhibited with 2,4 dinitrophenol or phloretin, or when stimulated with abscisic acid. In attempts to favour cellulose synthesis, no conditions were found where the ratio was substantially reduced. On the other hand, the ratio could be appreciably increased by inhibiting cellulose synthesis, e.g. with 2,6-dichlorobenzonitrile or coumarin, by anionic detergents such as sodium dodecyl sulphate, by low temperatures, or by increasing the osmotic strength of the incubation medium up to conditions causing plasmolysis. Specific degradation of callose, during incubation of the seed clusters, by exogenous exo-(1->3)-beta-D-glucanase significantly diminished incorporation of radioactivity into cellulose. PMID- 24240961 TI - Nitrite reduction in barley-root plastids: Dependence on NADPH coupled with glucose-6-phosphate and 6-phosphogluconate dehydrogenases, and possible involvement of an electron carrier and a diaphorase. AB - Plastids from roots of barley (Hordeum vulgare L.) seedlings were isolated by discontinuous Percoll-gradient centrifugation. Coinciding with the peak of nitrite reductase (NiR; EC 1.7.7.1, a marker enzyme for plastids) in the gradients was a peak of a glucose-6-phosphate (Glc6P) and NADP(+)-linked nitrite reductase system. High activities of phosphohexose isomerase (EC 5.3.1.9) and phosphoglucomutase (EC 2.7.5.1) as well as glucose-6-phosphate dehydrogenase (Glc6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) were also present in the isolated plastids. Thus, the plastids contained an overall electron-transport system from NADPH coupled with Glc6PDH and 6PGDH to nitrite, from which ammonium is formed stoichiometrically. However, NADPH alone did not serve as an electron donor for nitrite reduction, although NADPH with Glc6P added was effective. Benzyl and methyl viologens were enzymatically reduced by plastid extract in the presence of Glc6P+ NADP(+). When the plastids were incubated with dithionite, nitrite reduction took place, and ammonium was formed stoichiometrically. The results indicate that both an electron carrier and a diaphorase having ferredoxin-NADP(+) reductase activity are involved in the electron-transport system of root plastids from NADPH, coupled with Glc6PDH and 6PGDH, to nitrite. PMID- 24240962 TI - Validation of a radioimmunoassay for (+)-abscisic acid in extracts of apple and sweet-pepper tissue using high-pressure liquid chromatography and combined gas chromatography-mass spectrometry. AB - A radioimmunoassay for (+)-abscisic acid (ABA) was developed and applied to the analysis of free ABA in extracts of apple (Malus pumila Mill.) and sweet pepper (Capsicum annuum L.) leaves at various stages during extract purification. Conjugates of ABA, were quantified after alkaline hydrolysis. The validity of the radioimmunoassay was tested by comparison of immunoassay estimates of ABA at different levels of extract purity with high-pressure liquid chromatography (HPLC) and combined gas chromatography-mass spectrometry. The antiserum, raised against (+)-ABA, was almost equally sensitive to (-)-ABA. Serum cross-reactivity with the methyl ester of ABA was 160% and with the glycosyl ester of ABA was 34%. Cross-reactivity with protein-ABA conjugates was very slight for C'4-conjugated keyholelimpet haemocyanin, but about 1000% for C1-conjugated alkaline phosphatase. Other compounds tested showed extremely low or undetectable cross reactivities. Further evidence for the specificity of the assay came from the agreement between the results using different assay methods for both apple and pepper extracts, and from the observation that the only zone of immunoreactivity on HPLC elution profiles corresponded with authentic (+)-ABA. The use of polyvinylpyrrolidone in the assay minimised interference by other substances in plant extracts. In pepper, free ABA levels increased rapidly during water stress and recovered to pre-stress levels within two days after rewatering. Levels of ABA conjugates were significantly lowr than free ABA in unstressed plants, and also increased rapidly with stress, although not to the same extent as free ABA, and did not recover as rapidly as did free ABA. In apple, levels of free ABA and of ABA conjugates both increased more than twofold over a two-week period of water stress. In contrast to pepper, however, immunoreactivity of the conjugate fraction was increased by hydrolysis, indicating that different ABA conjugates predominate in the two species. PMID- 24240963 TI - Biosynthesis of glycoproteins involved in the pollen-stigma interaction of incompatibility in developing flowers of Brassica oleracea L. AB - De-novo synthesis of the S-allele-specific glycoproteins of Brassica oleracea is demonstrated in stigmas at different developmental stages. Excised stigmas incorporate (14)C-labeled amino acids into their S-glycoproteins early in development and before the self-incompatibility response is acquired, but the rate of synthesis accelerates prior to anthesis, resulting in the accumulation of high levels of the S-glycoproteins in the stigma and coinciding with the acquisition of the pollen-stigma incompatibility response. Since the self compatible and self-incompatible zones of developing inflorescences are very sharply delineated, a threshold quantity of S-glycoproteins appears to be critical for the onset of self-incompatibility. Incorporation experiments in which [(35S)methionine was applied to intact stigma surfaces indicate that the papillae are the main sites of synthesis of the S-specific glycoproteins. PMID- 24240964 TI - Conversion of [(14)C]gibberellin A 12-aldehyde to C 19- and C 20-gibberellins in a cell-free system from immature seed of Phaseolus coccineus L. AB - A cell-free system prepared from developing seed of runner bean (Phaseolus coccineus L.) converted [(14)C]gibberellin A12-aldehyde to several products. Thirteen of these were identified by capillary gas chromatography-mass spectrometry as gibberellin A1 (GA1), GA4, GA5, GA6, GA15, GA17, GA19, GA20, GA24, GA37, GA38, GA44 and GA53-aldehyde, all giving mass spectra with (14)C isotope peaks. GA8 and GA28 were also identified but contained no (14)C. All the [(14)C]GA12-aldehyde metabolites, except GA15, GA24 and GA53-aldehyde, are known endogenous GAs of P. coccineus. PMID- 24240965 TI - Monoclonal antibodies to a higher-plant nitrate reductase: Differential inhibition of enzyme activities. AB - A set of monoclonal antibodies has been raised against NADH-nitrate reductase (NR; EC 1.6.6.1) from spinach (Spinacea oleracea L.) leaves. Antibodies were screened by enzyme-linked immunosorbent assay and by their ability to inhibit various activities of the enzyme. The six monoclonals selected (AFRC MAC 74 to 79) are all gamma globulins; four (MAC 74 to 77) inhibit all terminal donating activities (NADH-NR; flavin mononucleotide, reduced form (FMNH2)-NR; and methyl viologen, reduced form (MV)-NR) and two (MAC 78 and 79) inhibit the acceptor activities (NADH-NR, and NADH-cytochrome c reductase). MAC 74 to 77 inhibit the NADH-NR activity of crude extracts of a variety of species (mono- and dicotyledoneae) while MAC 78 and 79 are effective against spinach and marrow, but not oil-seed rape, cucumber, oats, wheat and barley. PMID- 24240966 TI - Cell size and chloroplast size in relation to chloroplast replication in light grown wheat leaves. AB - As part of an investigation into the control of chloroplast replication the number and size of chloroplasts in mesophyll cells was examined in relation to the size of the cells. In first leaves of Triticum aestivum L. and T. monococcum L. the number of chloroplasts in fully expanded mesophyll cells is positively correlated with the plan area of the cells. The linear relationship between chloroplast number per cell and cell plan area is also consistent over a fivefold range of cell size in isogenic diploid and tetraploid T. monococcum. In T. aestivum the chloroplast number per unit cell plan area varies among cells in relation to the size of the chloroplasts. Those cells containing chloroplasts with a relatively small face area have a correspondingly higher density of chloroplasts, and consequently, the total chloroplast area per unit cell plan area is very similar in all the cells. The results indicate that the proportion of the cell surface area covered by chloroplasts is precisely regulated, and that this is achieved during cell development by growth and replication of the chloroplasts. PMID- 24240967 TI - Manipulation, by nutrient limitation, of the biosynthetic activity of immobilized cells of Capsicum frutescens Mill. cv. annuum. AB - The relationship between the synthesis and accumulation of protein and capsaicin was investigated in cultured cells of Capsicum frutescens Mill. cv. annuum immobilized in reticulate polyurethane. Cells were cultured in media containing reduced concentrations of essential nutrients, in an attempt to manipulate the rates of protein synthesis. Cells cultured in the absence of orthophosphate for 7 d demonstrated no reduction in the incorporation of L-[U-(14)C]phenylalanine into soluble protein or an increase in incorporation into capsaicin, compared with controls supplied with orthophosphate. By day 15 of culture, however, a differential incorporation of label was observed. Over a 21-d culture period the intracellular phosphate did not completely disappear. Cells cultured in the absence of nitrate and phosphate combined, however, exhibited some reduction in incorporation of [(14)C]phenylalanine into protein and an increased incorporation into capsaicin after 7 d of culture, but the differences were greater at day 15, when increases in the total capsaicin content of the cultures were apparent. There was observed a relationship between the intracellular nitrate concentration, the culture growth index, and the incorporation of [(14)C]phenylalanine into soluble protein - each of these factors was inversely related to the incorporation of label into capsaicin and the total capsaicin content of the cultures. PMID- 24240968 TI - Distribution and redistribution of extension growth along vertical and horizontal gravireacting maize roots. AB - Horizontal primary roots of Zea mays L. were photographed during the course of their gravireaction and during a preceding growth period in the vertical orientation. The displacement, by root elongation, of marker particles on the root surface was recorded. The particle-displacement rates were used to estimate the distribution of elemental elongation rates along opposite sides of the growing root apex. In the temperature range 21-25 degrees C there was a stimulation of local elongation rates along the upper side of a gravireacting root and a reduction (and sometimes a cessation) of elongation along the lower side. Elemental elongation rates have been related to the development of root curvature, and the magnitude of the differential growth between upper and lower sides required for a particular rate of bending has also been estimated. The results complement, and are compatible with, findings relating to the distribution of certain endogenous growth regulators believed to participate in the gravireaction. PMID- 24240969 TI - Androgenesis in Citrus aurantifolia (Christm.) swingle. AB - Embryoids were differentiated from anthers of C. aurantifolia which were first floated on a modified Murashige and Skoog's liquid medium supplemented with 0.5 mg/l N(6)-benzylaminopurine and 1 mg/l indole-3-acetic acid for 20-30 d, followed by 30 d culture in semisolid Schenk and Hildebrandt's medium having the same growth hormones. Embryoids originated from within the anther lobes. Initially, a few embryoids were formed by each anther; later, they multiplied rapidly by the production of new embryoids from the hypocotyl and cotyledon portions of the original embryoids. The embryoids could develop into plantlets, which were all diploid (2n=18). The androgenic plants grew normally in soil. PMID- 24240971 TI - Correction of kyphoscoliosis. PMID- 24240972 TI - Expectant versus surgical management of first-trimester miscarriage: a randomised controlled study. AB - INTRODUCTION: The aim of this study is to compare the efficacy and safety of expectant management with surgical management of first-trimester miscarriage. METHODS: This randomised prospective study was conducted in the Gynaecology Department at University of Saarland Hospital, Germany between February 2011 and April 2012. A total of 234 women were recruited following diagnosis of the first trimester incomplete or missed miscarriage and randomised into two groups: 109 women were randomised to expectant management (group I), and 125 women to surgical management (groupII). All women were examined clinically and sonographically during the follow-up appointments at weekly intervals for up to 4 weeks as appropriate. The outcome measures were: efficacy, short-term complications and duration of vaginal bleeding and pain. RESULTS: Of 234 eligible women, 17 were lost to follow-up, and the remaining 217 women were analysed. The baseline characteristics were similar in both groups. The total success rate at 4 weeks was lower for expectant than for surgical management (81.4 vs 95.7 %; P = 0.0029). The type of miscarriage was a significant factor affecting the success rate. For missed miscarriage, the success rates for expectant versus surgical management were 75 and 93.8 %, respectively. For women with incomplete miscarriage, the rates were 90.5 and 98 %. No differences were found in the number of emergency curettages between the two study groups. The duration of bleeding was significantly more in the expectant than the surgical management (mean 11 vs 7 days; P < 0.0001). The duration of pain was also more in the expectant than the surgical group (mean 8.1 vs 5.5 days; P < 0.0001). The total complication rates were similar in both groups (expectant 5.9 % vs surgical group 6.1 %; P = 0.2479). However, the pelvic infection was significantly lower in the expectant than the surgical group (1.9 vs 3.5 %, respectively; P = 0.0146). CONCLUSION: Expectant management of clinically stable women with first-trimester miscarriage is safe and effective and avoids the need for surgery and the subsequent risk of anaesthesia in about 81.4 % of cases, and has lower pelvic infection rate than surgical curettage. However, surgical management is more successful, and with a shorter duration of bleeding and pain. Therefore, the patient's preference should be considered in the counselling process. PMID- 24240973 TI - Immunogenicity/hypersensitivity of biologics. AB - This continuing education course was designed to provide an overview of the immunologic mechanisms involved in immunogenicity and hypersensitivity reactions following administration of biologics in nonclinical toxicity studies, the methods used to determine whether such reactions are occurring, and the associated clinical and anatomic pathology findings. Hypersensitivity reactions have classically been divided into type I, II, III, and IV reactions; type I and III reactions are those most often observed following administration of biologics. A variety of methods can be used to detect these reactions. Antemortem methods include hematology; detection of antidrug antibodies, circulating immune complexes and complement fragments, and immunoglobulin E in serum; tests for serum complement activity; and evaluation of complement receptor 1 on erythrocytes. Postmortem methods include routine light microscopy and electron microscopy, which can demonstrate typical findings associated with hypersensitivity reactions, and immunohistochemistry, which can detect the presence of immune complexes in tissues, including the detection of the test article. A final determination of whether findings are related to a hypersensitivity reaction in individual animals or across the entire study should rely on the overall weight of evidence, as findings indicative of these reactions are not necessarily consistent across all affected animals. PMID- 24240974 TI - Binding of pyrazole-based inhibitors to Mycobacterium tuberculosis pantothenate synthetase: docking and MM-GB(PB)SA analysis. AB - Recently, the search for new drugs against tuberculosis (TB) has been a hot topic and the search for new inhibitors against validated drug targets and pathways other than those currently targeted by known drugs is suggested to be the most promising way forward. Mycobacterium tuberculosis pantothenate synthetase (MTBPS) happens to be one of such targets. In a quest to carry out virtual screening for active inhibitors against MTBPS and to get ideas for the design of new inhibitors against this target, we have docked a set of pyrazole-based inhibitors to the active site of this enzyme. The docking solutions were post processed using the MM-PB(GB)SA method and molecular dynamic simulations in order to analyze and validate the two previously proposed binding modes. The results show that both the MM-PBSA and MM-GBSA were able to discriminate between active and inactive compounds. Moreover, the pharmacophore-based scoring method proved efficient in discriminating the active compounds from inactives. From this work a protocol for screening of potential inhibitors of the enzyme from commercially available databases has been devised. PMID- 24240975 TI - Successful management of acute myeloid leukemia transformed from myelodysplastic syndromes in an elderly patient aged over 80 years old by ultralow dose decitabine combined with amifostine and autologous CIK cells. PMID- 24240976 TI - DCEP for relapsed or refractory multiple myeloma after therapy with novel agents. AB - Multiple myeloma remains incurable despite the use of novel agents. Dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) is one of the salvage options, but there has been a lack of data on salvage DCEP in patients with previous exposure to novel agents. A total of 59 patients who received DCEP chemotherapy between 2006 and 2013 were retrospectively reviewed. The patients who had been exposed to thalidomide, lenalidomide, or bortezomib prior to DCEP were eligible. The median age at DCEP was 58 years, and DCEP treatment was initiated at a median of 34.9 months from diagnosis. Before DCEP, patients exposed to a median of three lines of treatment and 55 patients (81.4 %) had undergone autohematopoietic stem cell transplantation. Among 51 patients with data available for response assessment, response rate was 45.1 % (1 with complete response, 1 with very good partial response, and 21 with partial response); an additional 18 patients benefited from this regimen (8 with minor response and 10 stable diseases). Grade >=3 neutropenia was observed in 91.5 %. Treatment-related mortality (TRM) was reported in eight patients (14.8 %), and seven of eight deaths were related to febrile neutropenia. Median overall survival and progression-free survival were estimated at 8.0 and 3.7 months, respectively. DCEP is an effective salvage treatment options for relapsed or refractory multiple myeloma in the setting of previous use of novel agents. However, hematologic toxicities and TRM were substantial, and concurrent use of prophylactic granulocyte-colony stimulating factor is warranted. PMID- 24240977 TI - Immune status of Fanconi anemia patients: decrease in T CD8 and CD56dim CD16+ NK lymphocytes. AB - Fanconi anemia (FA), a rare genetic disease in which patients' life is compromised mainly by hematological abnormalities and cancer prone, seems to be affected by subtle immune cell irregularities. Knowing that FA presents developmental abnormalities and, based on recent reports, suggesting that natural killer (NK) CD56(dim) and NK CD56(bright) correspond to sequential differentiation pathways, we investigated if there were changes on the total number of NK cells and subsets as well as on T CD4 and T CD8 lymphocytes and their ratio. A large sample of FA patients (n = 42) was used in this work, and the results were correlated to clinical hematological status of these patients. Among FA patients, a decreased proportion of T CD8(+) and NK CD56(dim)CD16(+) cells were observed when compared to healthy controls as well as an imbalance of the subsets NK lymphocytes. Data suggest that FA patients might have a defective cytotoxic response due to the lower number of cytotoxic cells as well as impairment in the differentiation process of the NK cells subsets which may be directly related to impairment of the immune surveillance observed in these patients. PMID- 24240978 TI - A rare IgM multiple myeloma with aberrant PAX5 expression mimicking lymphoplasmacytic lymphoma. PMID- 24240979 TI - Ophiobolin-O reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human breast carcinoma (MCF-7/ADR) cells. AB - Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 +/- 0.05 uM and 74.00 +/- 0.18 uM treated MCF-7/ADR cells, about 37-fold, compared to the former. However, 0.1 uM Ophiobolin-O (less than 20% inhibition concentration) combined with ADM caused the decreased IC50 of ADM to 6.67 +/- 0.98 uM, indicating it reversed ADM resistance of MCF-7/ADR cells (11-fold). Furthermore, Ophiobolin-O increased ADM-induced mitochondrial pathway apoptosis and G2/M phase arrest, which is partly due to the elevation level of ROS in MCF-7/ADR cells. As we described in this paper, the reversal effect of Ophiobolin-O may be due to the reduction of resistance-related protein P-Glycoprotein (P-gp, also known as MDR1) through inhibiting the activity of the multidrug resistance 1 (MDR1) gene promoter, which makes MCF-7/ADR cells more sensitive to ADM treatment. Assays in nude mice also showed that the combination of ADM and Ophiobolin-O significantly improved the effect of ADM. PMID- 24240980 TI - Discovery of new eunicellin-based diterpenoids from a Formosan soft coral Cladiella sp. AB - A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Eunicellin 1 exhibited significant cytotoxicity toward the DLD 1 human colorectal adenocarcinoma cells. PMID- 24240981 TI - Bioprospecting marine plankton. AB - The ocean dominates the surface of our planet and plays a major role in regulating the biosphere. For example, the microscopic photosynthetic organisms living within provide 50% of the oxygen we breathe, and much of our food and mineral resources are extracted from the ocean. In a time of ecological crisis and major changes in our society, it is essential to turn our attention towards the sea to find additional solutions for a sustainable future. Remarkably, while we are overexploiting many marine resources, particularly the fisheries, the planktonic compartment composed of zooplankton, phytoplankton, bacteria and viruses, represents 95% of marine biomass and yet the extent of its diversity remains largely unknown and underexploited. Consequently, the potential of plankton as a bioresource for humanity is largely untapped. Due to their diverse evolutionary backgrounds, planktonic organisms offer immense opportunities: new resources for medicine, cosmetics and food, renewable energy, and long-term solutions to mitigate climate change. Research programs aiming to exploit culture collections of marine micro-organisms as well as to prospect the huge resources of marine planktonic biodiversity in the oceans are now underway, and several bioactive extracts and purified compounds have already been identified. This review will survey and assess the current state-of-the-art and will propose methodologies to better exploit the potential of marine plankton for drug discovery and for dermocosmetics. PMID- 24240982 TI - Durability enhancement of intermetallics electrocatalysts via N-anchor effect for fuel cells. AB - Insufficient durability and catalytic activity of oxygen reduction reaction (ORR) electrocatalyst are key issues that have to be solved for the practical application of low temperature fuel cell. This paper introduces a new catalyst design strategy using N-anchor to promote the corrosion resistance of electrocatalyst. The as-synthesized N-Pt3Fe1/C shows a high electrocatalytic activity and a superior durability towards ORR. The kinetic current density of N Pt3Fe1/C as normalized by ECSA is still as high as 0.145 mA cm(-2) and only 7% loss after 20,000 potential cycles from 0.6 to 1.2 V (vs. NHE) in O2-bubbling perchloric acid solution, whereas Pt3Fe1/C shows 49% loss under the same tests. The N-anchor approach offers novel opportunities for the development of ORR catalyst with excellent electrochemical properties. PMID- 24240983 TI - Accuracy of MRI in the diagnosis of meniscal tears in patients with chronic ACL tears. AB - PURPOSE: This study was conducted to evaluate the accuracy of magnetic resonance imaging (MRI) in diagnosing meniscal tears in patients with anterior cruciate ligament (ACL) tears and to determine the frequency of missed meniscal tears on MRI. METHODS: This prospective comparative study was conducted from 2009 to 2012. Patients with ACL injuries who underwent knee arthroscopy and MRI were included in the study. Two radiologists who were blinded to the clinical history and arthroscopic findings reviewed the pre-arthroscopic MR images. The presence and type of meniscal tears on MRI and arthroscopy were recorded. Arthroscopic findings were used as the reference standard. The accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of MRI in the evaluation of meniscal tears were calculated. RESULTS: A total of 65 patients (66 knees) were included. The sensitivity, specificity, accuracy, PPV, and NPV for the MRI diagnosis of lateral meniscal tears in our patients were 83, 97, 92, 96, and 90 %, respectively, whereas those for medial meniscus tears were 82, 92, 88, 82, and 88 %, respectively. There were five false-negative diagnoses of medial meniscus tears and four false-negative diagnoses of lateral meniscus tears. The majority of missed meniscus tears on MRI affected the peripheral posterior horns. CONCLUSION: The sensitivity for diagnosing a meniscal tear was significantly higher when the tear involved more than one-third of the meniscus or the anterior horn. The sensitivity was significantly lower for tears located in the posterior horn and for vertically oriented tears. Therefore, special attention should be given to the peripheral posterior horns of the meniscus, which are common sites of injury that could be easily missed on MRI. The high NPVs obtained in this study suggest that MRI is a valuable tool prior to arthroscopy. PMID- 24240984 TI - Influence of tibial rotation on tibial tunnel position measurements using lateral fluoroscopy in anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of the current study was to evaluate the influence of internal and external knee rotation on tibial tunnel position measurements in anterior cruciate ligament reconstruction using the Amis and Jakob line. METHODS: Anatomic double bundle ACL reconstruction was performed in seven cadaveric knees. Afterwards, the knees were CT scanned, and 3D CT models were established. Utilizing these models, strict lateral and radiographs with the knees in 5 degrees , 10 degrees , and 20 degrees of internal as well as external rotation were established. Using these radiographs, the positions of the anteromedial (AM) and posterolateral (PL) tibial tunnels were measured using the Amis and Jacob line. The tunnel positions of the strict lateral were compared to the rotated radiographs. To assess the inter- and intraobserver reliability, two independent observers measured the tunnel positions, and one observer measured twice. RESULTS: Significant differences for the AM tunnel position were observed if more than 10 degrees of external or 20 degrees of internal rotation were applied. For the PL tunnel position, no significant differences were found between the strict lateral and the rotated radiographs. Inter- and intraobserver reliability was good. CONCLUSIONS: The accuracy of the Amis and Jakob line is dependent on the degree of knee rotation and the position of the measured tunnel. Therefore, when using the Amis and Jakob line to determine the tibial tunnel position during surgery, attention should be paid to rotational alignment of lateral radiographs. However, the maximum rotation tested in the present study (20 degrees ) showed only a difference in tunnel position of 3.3 % compared to optimal rotational alignment. Thus, in most cases, the effects of minor malrotation on tunnel position measurement should be of minimal clinical significance. PMID- 24240985 TI - Postoperative respiratory failure: pathogenesis, prediction, and prevention. AB - PURPOSE OF REVIEW: This review discusses our present understanding of postoperative respiratory failure (PRF) pathogenesis, risk factors, and perioperative-risk reduction strategies. RECENT FINDINGS: PRF, the most frequent postoperative pulmonary complication, is defined by impaired blood gas exchange appearing after surgery. PRF leads to longer hospital stays and higher mortality. The time frame for recognizing when respiratory failure is related to the surgical-anesthetic insult remains imprecise, however, and researchers have used different clinical events instead of blood gas measures to define the outcome. Still, studies in specific surgical populations or large patient samples have identified a range of predictors of PRF risk: type of surgery and comorbidity, mechanical ventilation, and multiple hits to the lung have been found to be relevant in most of these studies. Recently, risk-scoring systems for PRF have been developed and are being applied in new controlled trials of PRF-risk reduction measures. Current evidence favors carefully managing intraoperative ventilator use and fluids, reducing surgical aggression, and preventing wound infection and pain. SUMMARY: PRF is a life-threatening event that is challenging for the surgical team. Risk prediction scales based on large population studies are being developed and validated. We need high-quality trials of preventive measures, particularly those related to ventilator use in both high risk and general populations. PMID- 24240986 TI - Cutaneous viral infections in patients after kidney transplantation: risk factors. AB - INTRODUCTION: Infectious skin lesions are a common complication in renal transplant patients receiving immunosuppressive therapy. OBJECTIVES: The aim of this study was to assess the prevalence and factors contributing to the development of viral skin infections in kidney transplant patients. PATIENTS AND METHODS: The study included 486 patients, 296 men (60.9%) and 190 women (39.1%), aged 46.1 +/-13.1 years, 74.3 +/-52.1 months post-transplantation, who remained mostly on triple immunosuppressive therapy. All skin lesions detected during the dermatological examination were described in detail, and the type, size, exact location, dependence on age, sex, and the used immunosuppressive therapy were established. Patients were followed for 5 years. RESULTS: Infectious skin lesions of viral origin were diagnosed in 189 of 486 patients (38.9%). The most frequent infections were viral warts (38.5%), which were more common in older patients (47.6 vs. 45.0 years, P <0.033). Viral warts were observed more often in men (P <0.031). Lesions of viral origin occurred more often in patients treated with immunosuppressive drugs for a longer period of time (53 vs. 37 months; P <0.021) and those who received azathioprine and cyclosporine A (P <0.001). In a multivariate logistic regression analysis, therapy with azathioprine was the only factor associated with increased risk of these complications (P <0.007). CONCLUSIONS: Older age, male sex, and longer duration of immunosuppressive therapy affect the incidence of infectious skin lesions in patients after kidney transplantation. Treatment with cyclosporine A and azathioprine promotes the development of infectious viral warts. PMID- 24240987 TI - Different effects of the mirror illusion on motor and somatosensory processing. AB - PURPOSE: Mirror therapy can improve motor and sensory functions, but effects of the mirror illusion on primary motor and somatosensory cortex could not be established consistently. METHODS: Fifteen right handed healthy volunteers performed or observed a finger-thumb opposition task. Cerebral activations during normal movement (NOR), mirrored movement (MIR) and movement observation (OBS) by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Activation sizes in movement > static conditions were identified using SPM8 (p < 0.001, unc.) and attributed to predefined areas employing the Anatomy toolbox 1.8. Laterality indices for the responsive areas were calculated on the basis of the number of activated voxels. RESULTS: Relevant bilateral BOLD responses were found in primary motor (M1) and somatosensory (S1 - BA 2, 3b and 3a) cortex, premotor and parietal areas and V5. When comparing MIR to NOR, no significant change of contralateral activation in M1 was found, but clearly at S1 with differences between hands. CONCLUSION: The mirror illusion does not elicit immediate changes in motor areas, yet there is a direct effect on somatosensory areas, especially for left hand movements. These results suggest different effects of mirror therapy on processing and rehabilitation of motor and sensory function. PMID- 24240990 TI - Genetics of the polycross : 1. Experimental results from Norway spruce. AB - Rates and patterns of male gamete incorporation for a polycross mating design were studied for two independent years of pollination in Norway spruce, Picea abies (L) Karst. Segregation distortion in a subset of maternal clones was documented for one locus. We have proposed a model, involving the existence of a linked lethal allele, which accounts for these observations. Significant temporal and maternal clonal differences were observed in the rates at which single locus and multilocus gametes were incorporated. Striking differences in apparent fertility existed among four clones which produced unique multilocus gametes. One clone, in particular, was shown to be contributing three times as many gametes to the next generation as predicted by the hypothesis of equal clonal male contribution. These deviations from expectation were also detected in the genotypic distributions of the resultant filial generation. Ramifications of these results on family structures in the filial generation, effective size of the male population, and possible bias in inferences of genetic differences and parameter estimation are discussed. PMID- 24240989 TI - The detection of different Dirofilaria species using direct PCR technique. AB - A novel direct PCR assay for the detection of Dirofilaria spp. from EDTA blood, Knott test, FTA cards, adult filarial worms, skin nodules and Dirofilaria spp. infected mosquitoes was tested. Larval and adult DNA of Dirofilaria spp. from FTA cards, from the mosquito vector and from worm fragments without prior DNA extraction was successfully obtained. As little as 3.11 larvae/100 MUl blood on FTA cards could be detected. Thus, direct PCR is capable of directly detecting first larval stages in the blood, third larval stages in the mosquito vector and pieces of mature stages of Dirofilaria spp. The assay is a rapid, sensitive and cost-effective alternative to standard PCR. PMID- 24240988 TI - Autophagy proteins regulate ERK phosphorylation. AB - Autophagy is a conserved pathway that maintains cellular quality control. Extracellular signal-regulated kinase (ERK) controls various aspects of cell physiology including proliferation. Multiple signalling cascades, including ERK, have been shown to regulate autophagy, however whether autophagy proteins (ATG) regulate cell signalling is unknown. Here we show that growth factor exposure increases the interaction of ERK cascade components with ATG proteins in the cytosol and nucleus. ERK and its upstream kinase MEK localize to the extra luminal face of autophagosomes. ERK2 interacts with ATG proteins via its substrate-binding domains. Deleting Atg7 or Atg5 or blocking LC3 lipidation or ATG5-ATG12 conjugation decreases ERK phosphorylation. Conversely, increasing LC3 II availability by silencing the cysteine protease ATG4B or acute trehalose exposure increases ERK phosphorylation. Decreased ERK phosphorylation in Atg5-/- cells does not occur from overactive phosphatases. Our findings thus reveal an unconventional function of ATG proteins as cellular scaffolds in the regulation of ERK phosphorylation. PMID- 24240991 TI - Beta chloroplast genomes: analysis of Fraction I protein and chloroplast DNA variation. AB - The interrelationships of Beta chloroplast genomes have been investigated on the basis of the analysis of Fraction I protein and chloroplast (ct) DNA. Three groups of the chloroplast genomes could be demonstrated by the difference in isoelectric points of the large subunit of Fraction I protein. Restriction enzyme analysis revealed inter- and intra-specific variations among the ctDNAs, which enabled us to detect seven distinct ctDNA types. In Vulgares and Corollinae species, the observed differences were physically mapped taking advantage of the restriction fragment map available for sugar beet (B. vulgaris) ctDNA. The DNA variations were found to result either from gains or losses of restriction sites or from small deletions/ insertions, and most of them were located in the large single-copy region of the genome. Moreover, the ctDNAs from Patellares species are more diverged from those of other Beta taxa. Our results also indicate that there is a close correlation between the chloroplast genome diversity and the accepted taxonomic classification of the species included in this survey. PMID- 24240992 TI - C-banding polymorphism and the analysis of nucleolar activity in Dasypyrum villosum (L.) Candargy, its added chromosomes to hexaploid wheat and the amphiploid Triticum dicoccum - D. villosum. AB - C-banding patterns and nucleolar activity were analyzed in Dasypyrum villosum, its added chromosomes to hexaploid wheat and the hexaploid amphiploid Triticum dicoccum-D. villosum. Two different populations of the allogamous species D. villosum (2n= 14, VV) from Greece and Italy were analyzed showing a similar polymorphism for C-banding pattern. Six of the seven addition lines were identified by their characteristic C-banding pattern. No polymorphism between both members of each added alien chromosome was found. Furthermore, nucleolar activity and competition were studied by using silver staining procedure. In D. villosum only one chromosome pair, A, was found to be responsible for organizing nucleoli. The results obtained in the amphiploid and in the addition lines demonstrate that nucleolar activity is restricted to SAT-chromosomes 1B and 6B of wheat, while those of D. villosum remain inactive. PMID- 24240993 TI - Linkage studies of the h gene with plant weight in flax genotrophs. AB - The association of the H-h (hairy-hairless septa) character with plant weight was studied in the coupling and repulsion phases in F2 of reciprocal crosses between large (L) and small (S) genotrophs of flax variety 'Stormont Cirrus'. F2 plants of reciprocal crosses in coupling (L(H) x S(h)) and in repulsion (L(h) x S(H)) giving H-h segregations were grown with their parents at two sowing times. Significant positive and negative associations between h and plant weight were obtained. A model is proposed based on the hypothesis that the H phenotype had changed to the h phenotype at the time of induction by a heterochromatic region extending over this locus. In the heterozygote, stable equilibria of the homozygotes are destroyed and transfer of heterochromatin, or number of reiterated sequences, or a decrease in one homologue and an increase in the other, occur in this region between homologous chromosomes. The amount and direction of the association is dependent upon the frequency of transfer: 0% transfer gives complete positive association; 50% transfer, no association; 100% transfer, complete negative association. This mechanism or heterochromatic transfer preserves the Mendelian ratio of 3?1 of H?h in the F2. It is also supposed that there must be other controlling elements present as well. PMID- 24240994 TI - Identification of restriction fragment length polymorphisms linked to genes controlling soluble solids content in tomato fruit. AB - Gene(s) conferring high soluble solids (SS) in tomato fruit had been backcrossed previously from a wild tomato species, Lycopersicon chmielewskii LA1028 (~ 10% SS), into a L. esculentum cultivar, VF36 (~ 5% SS), to derive a BC5S5 line, LA1563, similar to 'VF 36' but with 7-8% SS. DNAs from these lines and a tomato breeding line, H2038, were screened for restriction fragment length polymorphisms (RFLPs) using four restriction endonucleases and sixty clones chosen at random from a tomato cDNA library. Most of the cDNA clones (56) identified the same RFLP in 'VF 36' and LA1563 and a different RFLP in LA1028. However, two cDNA clones identified the same RFLP in LA1563 and LA1028 and a different RFLP in 'VF36'. To determine whether RFLPs identified by these two cDNA clones were linked to SS genes, a H2038 x LA1563 F2 population was screened for segregation of the RFLPs and for SS content. The segregation ratios of these RFLPs were consistent with ratios expected for codominant alleles at unlinked loci. Analysis of variance of SS content for different RFLP genotypic classes indicated that RFLP alleles at one of the loci were linked to genes controlling SS content. The RFLP allele from the high SS tomato line, LA1563, was associated with significantly higher SS content and, therefore, could be useful in selecting for high SS gene(s) in a tomato breeding program. PMID- 24240995 TI - Nucleotide sequence of the chloroplast gene responsible for triazine resistance in canola. AB - The nucleotide sequence for the psbA gene from a triazine resistant cultivar of B. napus (cv 'Triton') has been determined. This gene encodes an open reading frame of 353 amino acids that is highly homologous to other higher plant psbA genes at both the nucleotide and amino acid levels. As has been found for other triazine resistant psbA genes, the 'Triton' psbA contains an A to G nucleotide change which results in a serine to glycine amino acid substitution at position 264. The B. napus psbA gene also has a G insertion at position -9 resulting in a ribosome binding site sequence (AGGA) just before the initial methionine and suggesting that the entire open reading frame is translated. A large (72 bp) insertion is also found upstream of the B. napus psbA gene which resembles a similar insertion in the mustard psbA. The "uncloneable" nature of the entire gene is further investigated through reconstruction experiments and the implications discussed. PMID- 24240996 TI - A rapid, single leaf, nucleic acid assay for determining the cytoplasmic organelle complement of rapeseed and related Brassica species. AB - An assay is described whereby Eco RI restriction fragment length polymorphisms of mitochondrial and chloroplast DNAs can definitively identify cytoplasms of interest in Brassica crop development. Restrictable mitochondrial and chloroplast DNA is extracted from as little as 2-3 g and 0.5 g leaf tissue, respectively, and the donor plants are able to continue to develop in a normal manner. An unknown cytoplasm can be identified in three days, which is a considerable saving in time and labor compared to the several years required by traditional methods. The assay is very inexpensive and should be established as a routine procedure in laboratories involved in sexual or somatic Brassica hybrid production. PMID- 24240997 TI - Testcross selection theory. AB - The purpose of this paper is to extend the theoretical basis for testcross selection theory from models assuming two alleles per locus to a model which is general for number and frequency of alleles. The expectations of genetic variances expressed among and within testcross families is presented for both inbred and population testers. Predicted change due to selection in testcross, non-inbred and selfed population performance with testcross selection are derived. Expected changes in testcross heterosis and inbreeding depression in the population are also derived. Approximate confidence intervals for predicted selection response are developed and appropriate sets of progeny to evaluate in order to estimate parameters of interest are identified. PMID- 24240999 TI - Molecular analysis of the D-genome of the Triticeae. AB - The chromosome of three tetraploid Aegilops L. species containing the D-genome were analyzed by in situ hybridization with a repeated DNA sequence clone pAS1 isolated from Aegilops squarrosa and observed to be D-genome specific. This sequence is found on all seven D-genome chromosome pairs of A. squarrosa and hexaploid wheat. Two distinct D-genome patterns were observed in the tetraploid species. The D-genome of A. cylindrica was similar to hexaploid wheat. Seven pairs of chromosomes having large amounts and numerous sites of the sequence were observed. Five chromosome pairs with fewer and smaller sites of the repetitive sequence were observed in the D-genomes of A. crassa and A. ventricosa. In addition to these major repeated sequence differences, chromosomal modifications appear to have occurred between T. aestivum and A. cylindrica and between A. crassa and A. ventricosa resulting in changes with respect to location of the sequence between the respective species. D-genome divergence with respect to pAS1 sequence appears to have occurred at least in two forms, one characterized by the changes in amount of repetitive sequence and the second by changes in location of the sequence. PMID- 24240998 TI - Somatic hybrids between Brassica oleracea and B. campestris: selection by the use of iodoacetamide inactivation and regeneration ability. AB - An efficient procedure for obtaining somatic hybrids between B. oleracea and B. campestris has been developed. Hypocotyl protoplasts of B. oleracea were fused with mesophyll protoplasts from three different varieties of B. campestris by the polyethylene glycoldimethylsulfoxide method. The selection of somatic hybrids utilized the inactivation of B. oleracea protoplasts by iodoacetamide (IOA) and the low regeneration ability of B. campestris. The efficiency of recovery of somatic hybrids depended upon the IOA concentration, and when 15 mM IOA was used, 90% of the regenerated plants were found to be hybrid. The somatic hybrids were examined for i) leaf morphology, ii) leucine aminopeptidase (LAP) isozyme and iii) chromosome number. All the hybrids had intermediate leaf morphology and possessed LAP isozymes of both parental species. The chromosome analysis revealed a considerable variation in chromosome number of somatic hybrids, showing the occurrence of multiple fusion and chromosome loss during the culture. Some of the hybrids flowered and set seeds. PMID- 24241000 TI - Plant regeneration from cultured immature embryos of Sorghum bicolor (L.) Moench. AB - Immature embryos of 20 sorghum genotypes were cultured on MS 5 medium containing MS mineral salts supplemented with 2,4-D, zeatin, glycine, niacinamide, Ca pantothenate, L-asparagine, and vitamins. For regeneration, calli were transferred onto the same medium with the exception that IAA was substituted for 2,4-D. In general, immature embryos obtained 9-12 days after pollination resulted in the best redifferentiation. Ability of calli to regenerate varied among genotypes; cultivars C401-1 and C625 had the highest redifferentiation frequencies. Ability to redifferentiate was heritable and acted as a dominant trait. At least two gene pairs were involved. Regenerated R0 plants were planted in a greenhouse and their selfed (R1 and R2) progenies were planted in the field and examined for morphological and cytological variations. The majority of the phenotypic variations noted in R0 were not transmitted to later generations. However, variants for plant height, degree of fertility, and midrib color persisted in R1 and R2 generations. A variation in tallness was attributable to one dominant mutant gene. Short stature and male sterility variants appeared to be consequences of recessive mutant genes controlling those traits. Minor variations in peroxidase banding patterns were found among R0 plants. PMID- 24241001 TI - Fertility of somatic hybrids from protoplast fusions of Solanum brevidens and S. tuberosum. AB - Two sets of somatic hybrids between Solanum brevidens (2x) and S. tuberosum (2x and 4x) were evaluated for male fertility, meiotic regularity and female fertility. The somatic hybrids were tetraploids from 2x + 2x fusions and hexaploids from 2x + 4x fusions. Pollen stainability ranged from 0 to 83% in tetraploids and from 0 to 23% in hexaploids. The tetraploids had more regular meiosis, lower levels of micropollen and fewer unassociated chromosomes than hexaploids. However, except for a low level of selfing, the pollen of both sets of hybrids was ineffective in pollinations. The tetraploids, as females, crossed poorly with 2x and 4x tester species and selfed only at low levels. The hexaploid fusion hybrids also crossed poorly with the 2x tester species and selfed only to a limited degree; however, they crossed well with 4x testers. Seed set in crosses with S. tuberosum Group Andigena, and S. tuberosum Group Tuberosum cultivars 'Kathadin' and 'Norland' averaged 16.7, 15.6 and 28.6 seeds per fruit, respectively. Progeny from these crosses had 5x or nearly 5x ploidy levels. The results indicate that reasonable levels of female fertility can be obtained in somatic fusion hybrids of S. brevidens and S. tuberosum. PMID- 24241002 TI - The effect of the crossability loci Kr1 and Kr2 on fertilization frequency in hexaploid wheat x maize crosses. AB - Dominant alleles of the Kr1 and Kr2 genes reduce the crossability of hexaploid wheat with many alien species, including rye and Hordeum bulbosum, with Kr1 having the greater effect. However, a cytological study of wheat ovaries fixed 48 h after pollination showed that the wheat genotypes 'Highbury' (kr1, Kr2) and 'Chinese Spring (Hope 5B)' (kr1, kr2) were crossable with 'Seneca 60' maize, fertilization occurring in 14.4 and 30.7% of embryo sacs respectively. The latter figure was similar to the 29.7% fertilization found in 'Chinese Spring' (kr1, kr2). Most embryo sacs in which fertilization occurred contained an embryo but lacked an endosperm and where an endosperm was formed it was usually highly aberrant. All three wheat x maize combinations were karyotypically unstable and rapidly eliminated maize chromosomes to produce haploid wheat embryos. PMID- 24241003 TI - The inheritance of a urease-null trait in soybeans. AB - Four soybean seed urease nulls (lacking both the activity and antigen of the embryo-specific urease) were intermated and the F1 and F2 seed examined for urease activity. Both generations were without urease activity, and the nulls were therefore considered noncomplementing. In crosses of each null line to cultivars homozygous for the allelic, codominantly inherited urease slow or fast isozyme, the F1 seed expressed the embryo-specific urease isozyme of the urease expressing parent. A 3 ? 1 segregation for presence and absence of urease was observed in progeny from F1 and heterozygous F2 plants. The F2 and F3 from fastXnull combinations revealed that urease-positive seed were all phenotypically urease fast, while the same seed from slowXnull combinations showed a segregation of one seed containing a fast urease, either exclusively or in a heterozygous state with the slow isozyme, for every 69 phenotypic slows. Data pooled from F2 plants which segregate for both the presence (Sun) and absence (Sun) of urease and for the fast (Eu1-b) or slow (Eu1-a) urease allele indicate that the null lesion (Sun) is linked to Eu1 by approximately one map unit. The evidence is consistent with two models: (1) sun is an allele at the embryo-specific urease isozyme locus (Eu1) and that a high degree of exchange (and/or conversion) within the locus results in a 1% recombination frequency between the null trait and urease allozyme; (2) sun is at a distinct locus which is separated by one map unit from the embryo-specific urease isozyme locus (Eu1) upon which it acts in the cis position. Polyadenylated embryo RNA from one of the null lines, PI 229324, exhibited no urease template activity in vitro. Thus, the lack of urease antigen is due to lack of accumulation of translatable urease mRNA. The availability of soybeans lacking seed urease should be extremely useful to breeders as a trait for linkage studies and to geneticists as a transformation marker. PMID- 24241004 TI - Biochemical polymorphism in relation to performance in horses. AB - Investigations on relationships between biochemical polymorphism and variation in quantitative traits are of interest from the perspectives of both theoretical quantitative genetics and practical animal breeding. This subject was studied by using racing performance records of more than 25,000 horses of the Swedish Trotter breed born in the period 1970-1979. For all horses data on six blood group and nine electrophoretic loci were available. Two different performance traits were investigated. A racing performance index value was calculated for all individuals which had started in at least five races. Horses which had not started at all or less than five times were pooled in an unstarted class and the proportion of started horses was analysed as an all-or-none trait. The relationships between the marker genes and these two performance traits were analysed statistically by using linear models. Analysis within sires revealed a very highly significant association between variation at the serum esterase locus (Es) and the proportion of started horses. In addition, four weakly significant associations were found. A striking feature of the highly significant association involving the esterase locus was that the effect of different alleles showed a good fit to an additive genetic model as the value of each heterozygous type was intermediate to the two corresponding homozygotes. In addition to the association tests, the possibility of genetic linkage between marker genes and genes affecting performance was tested as well as the influence on performance of heterozygosity at marker loci. No significant relationships were revealed in these latter tests. PMID- 24241005 TI - The occurrence of Ds-like sequences in cereal genomes. AB - The occurrence of DNA sequences similar to the Ds-element of sh-m5933 maize (Ds like sequences) was studied in other representatives of the Gramineae. The approximate number of copies of such sequences found under gentle and stringent conditions of washing was determined by dot-hybridization. It was shown that in the maize genome the number of copies of Ds-like sequences exceeds about ten-fold the content of such sequences found in wheat, rye and barley genomes. Quantitative differences in Ds-like sequences between wheat species with various genomes and ploidies (when estimated per genome) as well as between different H. vulgare varieties was not determined. The various melting points (Tm) of DNA duplexes formed when the Ds-element is hybridized with wheat, rye and barley DNA respectively do not show significant differences and are essentially lower than the Tm of the Ds-element (by 8 degrees -9 degrees C). Thus, these duplexes have 9 11% of nucleotide substitutions in comparison to Ds sh-m5933. The data obtained permit one to suppose the presence of a series of Ds-like sequences heterogenous for the length and degree of homology to the Ds-element isolated from the shrunken locus (sh-m5933) of maize DNA. PMID- 24241006 TI - Chromosomal location of structural genes controlling isozymes in Hordeum chilense : 1. 6-Phosphogluconate dehydrogenase and malate dehydrogenase. AB - A study of 6-phosphogluconate dehydrogenase and malate dehydrogenase isozyme expression in Triticum turgidum conv. durum /Hordeum chilense monosomic addition lines has revealed the location of two structural genes, 6-pgd-H (ch) 2 and Mdh-H (ch) 1, on chromosome 1H(ch) of H. chilense. The homoeology between 1H(ch) and other chromosome of Triticeae related species is discussed on the basis of isozyme gene analysis. PMID- 24241007 TI - Genetics of alpha-amylases from rye endosperm. AB - Fifteen inbred lines of rye, F1 and F2 progenies from crosses between lines were studied using polyacrylamide gel electrophoresis. Conventional genetic analysis of alpha-amylase zymograms showed that the 19 bands detected in the endosperm of germinating caryopses were controlled by three linked structural loci and one independent modifying locus, which influenced the electrophoretic mobility of isozymes. Two codominant alleles were found at the alpha-Amy1, alpha-Amy2 structural loci and the M-alpha-Amy modifying locus while the alpha-Amy3 locus had three alleles. Double-banded expression of the alpha-amylase alleles was probably due to the simultaneous presence of modified and unmodified forms of isozymes on the zymogram. PMID- 24241008 TI - Heterosis among populations of maize (Zea mays L.) with different levels of exotic germplasm. AB - Thirteen maize (Zea mays L.) populations including five adapted, five adapted x exotic, two composites of adapted and exotic, and one exotic selected for adaptability were crossed in a diallel mating system. The parents and 78 crosses and nine check hybrids were evaluated for grain yield and plant height in five environments. The Gardner-Eberhart model Analysis II indicated that additive and nonadditive gene effects accounted for 60 and 40% of the total variation among populations, respectively, for grain yield and 86% and 14% of the total variation, respectively, for plant height. Components of heterosis were significant in the combined analysis for both traits. Adapted Corn Belt populations tended to have higher performance in crosses and greater values of variety heterosis than 50% adapted populations. 'Nebraska Elite Composite', 'Corn Belt' x 'Mexican', and 'Corn Belt' x 'Brazilian' showed high mean yields in crosses, however, they were not among those with high estimates of variety heterosis. One exotic population ('Tuxpeno' x 'Antigua Grupo 2') and three adapted populations ['307 Composite', 'NB(S1)C-3', and 'NK(S1)C-3'] might be combined together to form a high-yielding population. It may be possible to synthesize two useful populations for reciprocal recurrent selection by grouping 'Tuxpeno' x 'Antiqua Grupo 2', 'NB(S1)C-3', and 'NS(FS)LFW-8' into one population and 'NK(S1)C-3', 'Krug'x'Tabloncillo', and '307 Composite' in the other one. PMID- 24241009 TI - Somatic hybridization of amino acid analogue-resistant cell lines of potato (Solanum tuberosum L.) by electrofusion. AB - Intraspecific somatic hybridization between amino acid analogue-resistant cell lines of potato (Solanum tuberosum L.) has been carried out following electrofusion of protoplasts. In initial analytical electrofusion experiments (1 mm electrode separation) optimal fusion conditions were determined by changing the fusion medium (addition of Ca and/or spermine) and the electrical parameters. Subsequently, in large scale experiments, cell suspension protoplasts of aec-1, a variant resistant to AEC, were fused with the same type of protoplasts of 5mt-26 or 5mt-27, both variants resistant to 5MT and cross-resistant to 3 FT. After an extensive selection procedure only somatic hybrid lines of aec-1 + 5mt-26 were obtained. The resistance traits of aec-1 and 5mt-26 were expressed fully, indicating that the variant characters involved are transmitted dominantly. Quantitative examination of the free amino acid content revealed characteristics of both the parental cell lines in most of the somatic hybrids. However, initially selected double resistant colonies from fusions of aec-1 + 5mt-27 lines appeared not to be somatic hybrids. PMID- 24241010 TI - A somaclonal variant of wheat with additional beta-amylase isozymes. AB - The progeny of 149 plants regenerated from tissue culture of immature wheat (Triticum aestivum) embryos were screened for variation in their grain beta amylase isozyme pattern. One regenerant was found which was heterozygous for a variant pattern characterized by the presence of at least five new isozyme bands, as well as an increased intensity in existing bands in two more positions. The F2 of a homozygous variant crossed back to the parent segregated in an approximate 3?1 ratio but resolution of the gels was not sufficient to distinguish whether this represents a dominant or co-dominant single mutant gene. No chromosome abnormalities were evident in mitosis or meiosis of the homozygous variant or in the F1 of the variant crossed back to the parent. No recombination has been seen between the variant bands and production of multiple bands from a single locus is consistent with the nature of the known beta-amylase loci. However, the variant bands were not evident in a survey of 111 diverse genotypes, nor were they present in developing grain of the parent cultivar. Therefore, this variant could represent a rare mutation leading to expression of a currently unexpressed locus. PMID- 24241011 TI - Artificial Brassica napus flowering in Bangladesh. AB - Natural rapeseed (Brassica napus L.; AACC 2n=38), originated in the temperate climate of the Southwest European Mediterranean region, fails to complete its generative phase in the subtropics and is thus not cultivated in countries like Bangladesh. Adapted agroecotypes are available from the diploid representatives of its genome A (B. campestris/pekinensis, 2n=20) and C (B. oleracea/alboglabra, 2n=18). An artificial resynthesis based on carefully selected progenitor lines was expected to give a photoperiodically better adapted rapeseed. ? B. pekinensis x ? B. oleracea/alboglabra gave 2 hybrids and 87 matromorphous plants from 1,448 crossed flowers and the reciprocal combination gave no hybrid but 11 matromorphous plants from 2,228 pollinated flowers. The two true hybrids were vegetatively propagated and chromosome doubled. Part of the F2 was grown in Sweden (all plants flowered and the most early ones were selected), part in Bangladesh (13 out of 706 plants flowered). The selected F3 material flowered in Bangladesh and transgressions in earliness could be recorded, some lines were of definite agronomic potential. A correlation in earliness between reaction in Sweden (long day) and Bangladesh (short day) was observed. PMID- 24241012 TI - Sister chromatid exchange points in the heterochromatin and euchromatin regions of Chinese hedgehog chromosomes. AB - The Chinese hedgehog has a diploid chromosome number of 48 in which there are eleven pairs of telo- or subtelocentric autosomes, twelve pairs of meta- or submetacentric autosomes, a metacentric X chromosome and a telocentric Y chromosome. The heterochromatin is almost completely distributed in five large distal segments of chromosomes nos. 9 to 12 and no. 18. There is no positive C band in the centromeres of the chromosomes except for the X chromosome which has a small, weakly stained C-band in the centromere. In Chinese hedgehog cells 52.1% of SCEs are found at the junction between the euchromatin and the heterochromatin, 39.5% in the heterochromatin and 8.4% in the auchromatin. The SCE number per unit C-band is double the SCE number per unit euchromatin. The SCE rate in the heterochromatin or euchromatin regions is not proportional to their chromosome length and can be quite different between different pairs of the chromosomes. Our results indicate that there is a non-uniform distribution of the SCEs in the Chinese hedgehog cells. PMID- 24241013 TI - Heritability estimates of citral content in East Indian lemongrass. AB - Citral content in oil obtained from 80 representative clones, chosen randomly from a population raised from open-pollinated seeds of clonally propagated East Indian lemongrass variety 'SD-68' and their half-sib progenies was estimated by gas chromatography. Heritability estimates were determined by variance component and parent-offspring regression analyses. Broad-sense heritability was 0.49 while narrow sense heritabilities by variance and regression analyses were 0.37 and 0.24, respectively. Phenotypic and genotypic correlations between citral content in oil and oil content were very low both among the parental clones (-0.01 and 0.01, respectively) and among their progenies (0.13 and 0.08, respectively) indicating that selection for either of these traits would not have much effect on the other. PMID- 24241015 TI - Modification of the interaction betweenEscherichia coli and bacteriophage in saline sediment. AB - The effects of sorption phenomena on the interaction between a parasite and its host bacterium have been investigated using anEscherichia coli-bacteriophage saline sediment system. The sediment contained organic matter and a high proportion of clay, predominantly montmorillonoid. BothE. coli and phage remained firmly sorbed to saline sediments or montmorillonite, but were rapidly desorbed following dilution of the electrolyte below a critical concentration. This desorption coincided with the dispersal of sediment colloids.Escherichia coli was protected from phage attack by the presence of sediment, montmorillonite, or organic matter at salinty levels both above and below this critical point for dispersal and desorption. Evidence is presented indicating thatE. coli is protected from phage attack at low electrolyte concentrations by an envelope of sorbed colloidal materials around the cell, whereas at high electrolyte concentrations protection results both from the colloid envelope around the cells as well as from the sorption of cells and phages to solid particles. The protection ofE. coli and possibly other fecal bacteria may result in their accumulation in saline sediments, producing a possible health hazard in estuaries and lagoons if the bacteria are desorbed following dilution as a result of heavy rainfall. PMID- 24241014 TI - The relationship of symptomatic thoracolumbar disc herniation and Scheuermann's disease. AB - PURPOSE: Symptomatic disc herniations in the thoracolumbar spine between T10/11 and L1/2 can be collectively called thoracolumbar disc herniation (TLDH). The etiology of this disorder is unclear. However, it is interesting that we have noted numerous TLDH patients have radiographic features of another spinal disorder which is Scheuermann's disease (SD). The purpose of this study is to investigate the relationship between symptomatic TLDH and SD in a symptomatic TLDH cohort. METHODS: A cohort of 63 patients with symptomatic TLDH, who had surgery was investigated. Incidences of associated SD and four radiographic signs of SD that were Schmorl's node, irregular vertebral end plate, posterior bony avulsion of the vertebra and wedge-shaped vertebra, average thoracolumbar kyphotic angle and incidences of disc herniation at segments with and without radiographic signs of SD were examined. Data from the TLDH group were compared with 57 patients undergoing surgery for lower lumbar disc herniation (LDH, L3/4 L5/S1) in the same period. RESULTS: The incidences of the four radiographic signs of SD and the incidence of associated SD were all significantly higher in the TLDH group than in the LDH group. 95.2 % of the patients in the TLDH group were diagnosed with SD (either classical SD or its atypical form). The average thoracolumbar kyphotic angle of the TLDH group was 16.9 degrees , while that of the LDH group was 7.6 degrees (P = 0.000). In the TLDH group, the incidences of disc herniation at segments with radiographic signs of SD were all significantly higher than at segments where no sign of SD was found. CONCLUSIONS: The high proportion of associated SD and the tendency of SD's signs to promote disc herniation in symptomatic TLDH patients suggest a close relationship between these two disorders. Symptomatic TLDH should be seen as a truly different surgical entity, that is, a special form of SD rather than just an indicator of a failing back. PMID- 24241016 TI - Scanning electron microscopy of microorganisms on the roots of wheat. AB - The scanning electron microscope was used to study the microorganisms on wheat roots grown in both soil and sand. Bacteria became common on the root surface only in the root hair region of young roots; nearer the tip of the root they were rare. Older roots had relatively high populations of bacteria. Bacteria were sometimes embedded in mucilage, of either plant or microbial origin, which seemed to bind the bacteria firmly to the root surface. Mineral grains on or near the roots of wheat were generally free of mucilage. PMID- 24241017 TI - Microbial transformations of some(14)C-labeled substrates in coastal water and sediment. AB - In order to complement data obtained from earlier deep-sea studies on microbial transformations, similarin situ incubation experiments were done in shallow coastal waters. Compared to laboratory controls,in situ activities were reduced about 50%, in contrast to about 99% previously reported for samples incubated in the deep sea. PMID- 24241018 TI - Effects of PCB on interspecific competition in natural and gnotobiotic phytoplankton communities in continuous and batch cultures. AB - The toxicity of polychlorinated biphenyls (PCB) to the diatomThalassiosira pseudonana (formerlyCyclotella nana), grown in pure and mixed cultures, was greatest when in competition with other species. Continuous cultures were superior to batch cultures for studying competitive interactions, and PCB caused greater alteration of species composition in continuous cultures than it did in batch cultures. Natural phytoplankton communities from Vineyard Sound, maintained in continuous culture, responded to PCB stress the same as did gnotobiotic communities, withT. pseudonana showing similar responses in both communities.A PCB concentration of 0.1 MUg/liter (0.1 part per billion), a level not uncommon in natural waters, did not affect algal growth in pure cultures but caused substantial disruption of continuous culture communities. The possible impact of PCB pollution on natural phytoplankton communities is discussed. PMID- 24241019 TI - The identification of gas vacuoles and their abundance in the hypolimnetic bacteria of Arco Lake, Minnesota. AB - Bright refractile granules in bacterial cells are identified as gas vacuoles if they disappear on application of a few atmospheres pressure. This paper describes a simple method for observing individual cells under the light microscope before and after application of pressure and the use of this method in making a comprehensive survey of gas-vacuolate organisms in a sample. In water samples from the hypolimnion of a stratified lake (Arco Lake) in Northern Minnesota, gas vacuoles were found in nearly 30 different bacteria, representing possibly 60% or more of those present. The pressure sensitivity of gas vacuoles in these organisms is illustrated by micrograph pairs. Gas vacuoles, which are otherwise uncommon in bacteria, are evidently of great selective value in the hypolimnia of stratified lakes, perhaps by regulating cell buoyancy. PMID- 24241020 TI - Microbial degradation of model petroleum at low temperatures. AB - Two areas of Chesapeake Bay, Colgate Creek in Baltimore Harbor and Eastern Bay, are presently under study, with routine sampling of water and sediment for petroleum-degrading microorganisms (bacteria, yeasts, and fungi) by direct plating and enrichment culture. Selected physical and chemical parameters are recorded for each sampling site, and water and sediment samples are extracted for hydrocarbons. Numbers of petroleum-degrading microorganisms enumerated by direct plating were found to correlate with the concentration of benzene-extractable material and were higher for the Colgate Creek than for the Eastern Bay site. Petroleum-degrading microorganisms were isolated from water and sediment samples at environmental temperatures of 0 degrees , 5 degrees , and 10 degrees C.A salts medium supplemented with nitrate and phosphate was used to provide optimum conditions for petroleum degradation, whereas Chesapeake Bay water was used to simulate natural environmental conditions. Use of a model petroleum permitted quantitative measurement of utilization of individual hydrocarbons ranging in complexity from simple alkanes to polynuclear aromatic hydrocarbons. Higher growth yields and maximum hydrocarbon degradation was observed for microorganisms in the salts medium at 0 degrees , 5 degrees , and 10 degrees C, although significant quantities of hydrocarbons were utilized in some samples grown in a medium for which Chesapeake Bay water was the diluent. Bacterial hydrocarbon degradation accounted for most of the model petroleum utilization at 0 degrees and 5 degrees C. However, oscillations of bacterial populations, with significant growth of yeasts, was observed at 10 degrees C. Photomicroscopy and scanning electron microscopy revealed aggregates of bacteria, yeasts, and fungi associated with oil globules. From preliminary identification and classification of the hydrocarbon-utilizing bacteria, members of the generaVibrio, Aeromonas, Pseudomonas, andAcinetobacter were present in the enrichment cultures. From results of this study, it is concluded that utilization of model petroleum at low temperatures is a function of the types and numbers of microorganisms present in an original inoculum taken from the natural environment. PMID- 24241021 TI - Decomposition of deciduous leaf litter in a woodland stream : I. A. Scanning electron microscopic study. AB - Microorganisms associated with decomposing deciduous leaf litter in a woodland stream were examined by scanning electron microscopy. The use of a critical point drying method allowed the preservation of a wide variety of microorganisms as well as the decomposing litter with a minimum of distortion. The micrographs provide evidence that the aquatic hyphomycetes are the major fungal flora present during decomposition. Two distinct groups of these fungi were found during the seasonal cycle with one group occurring only in the summer while the other occurred throughout the rest of the year. The presence of all developmental stages of these organisms in the environment is considered further evidence of their active role in the decomposition of litter. PMID- 24241022 TI - Coexistence of organisms competing for the same substrate: An example among the purple sulfur bacteria. AB - The purpose of this study was to find a possible explanation for the coexistence of large and small purple sulfur bacteria in natural habitats. Experiments were carried out withChromatium vinosum SMG 185 andChromatium weissei SMG 171, grown in both batch and continuous cultures. The data may be summarized as follows: (a) In continuous light, with sulfide as growth rate-limiting substrate, the specific growth rate ofChr. vinosum exceeds that ofChr. weissei regardless of the sulfide concentration employed. Consequently,Chr. weissei is unable to compete successfully and is washed out in continuous cultures. (b) With intermittant light-dark illumination, the organisms showed balanced coexistence when grown in continuous cultures. The "steady-state" abundance ofChr. vinosum was found to be positively related to the length of the light period, and that ofChr. weissei to the length of the dark period. (c) Sulfide added during darkness is rapidly oxidized on subsequent illumination, resulting in the intracellular storage of reserve substances, which are later utilized for growth. The rate of sulfide oxidation/mg cell N/hr was found to be over twice as high inChr. weissei as inChr. vinosum. The observed coexistence may be explained as follows. In the light, with both strains growing, most of the sulfide will be oxidized byChr. vinosum [see (a)]. In the dark, sulfide accumulates. On illumination, the greater part of the accumulated sulfide will be oxidized byChr. weissei [see (c)]. A changed light-dark regimen should then have the effect as observed [see (b)]. These observations suggest that intermittant illumination may, at least in part explain the observed coexistence of both types of purple sulfur bacteria in nature. PMID- 24241023 TI - Refractive index of uranyl-treated bacterial cytoplasm as related to ribonucleic acid content and growth rate. AB - After fixation and treatment with uranyl acetate solutions, the refractive index (n D) of the cytoplasm ofCorynebacterium bovis varies with substrate-dependent growth rate and RNA content. The effect, which presumably is due to quantitative binding of uranyl ions by RNA, permits a measurement of the growth rate of single cells in a single-species system by interference microscopy. Temperature-induced changes in growth rate are not reflected in changes ofn D or RNA content. PMID- 24241024 TI - Vibrio parahaemolyticus andVibrio alginolyticus: Short generation-time marine bacteria. AB - The growth rates of 30 different strains ofVibrio parahaemolyticus andVibrio alginolyticus at 37 degrees C was determined. Each species consists of two major groups, one having a short generation time (12-14 min) and one with a longer generation time (20-25 min). The diversity in generation times of different strains belonging to the same species is discussed. The effect of temperature, salt, and nutrient concentrations on the growth rate of oneV. alginolyticus strain (NCMB 1803) was studied. The most striking is the effect of the temperature; at 39 degrees C the generation time is 10-11 min, while at 21 degrees C it is 60 min. The heat of activation for growth calculating from such data is 22,580 kcal/mole/hr(-1). The ecological significance of these results is discussed. PMID- 24241025 TI - Factors affecting trimethylarsine and dimethylselenide formation byCandida humicola. AB - Selenite, selenate, and tellurate inhibited the conversion of arsenate to trimethylarsine byCandida humicola. Trimethylarsine disappeared from the gas phase when incubated withC. humicola in the presence of selenium or tellurium salts. The fungus generated dimethyl-selenide from selenite and selenate and an unidentified gas from tellurate. Sulfate but not arsenate, tellurate, or phosphate inhibited the conversion of selenate to dimethylselenide. Arsenate grown cells generated trimethylarsine from arsenate, and selenate-grown cells formed dimethylselenide from selenate with almost no lag phase. Cells grown in media with selenate or with no additions only formed the alkylarsine from arsenate after a lag phase, and those grown in solutions with arsenate or no additions produced dimethylselenide slowly from selenate. PMID- 24241026 TI - Applicability of radiotracer methods of measuring(14)CO 2 assimilation for determining microbial activity in soil including a newin situ method. AB - The applicability of two methods (pyrolysis gas chromatography and acidification wet oxidation) for determining(14)CO2 incorporation into soil microorganisms was investigated. Both methods were able to distinguish biologically incorporated(14)C from abiotically adsorbed(14)C, but to varying degrees, there being a larger carryover of abiotic(14)C into the organic fraction and a higher percentage of assimilated(14)C in the organic fraction with the wet oxidation method. Using(14)C assimilation as a measure, it was possible to determine microbial activities in soils of diverse properties under a variety of conditions, including polar soils under harsh environmental conditions. Both light and dark(14)CO2 fixation was measurable.(14)CO2 assimilation was not always proportional to the enumerable microorganisms. A new design for measurement of microbial activityin situ enabled measurement of total C influx (primary productivity) into soils with minimal perturbation to the natural soil ecosystem. PMID- 24241027 TI - Kinetics of phosphorus absorption byCorynebacterium bovis. AB - The initial rate of phosphorus uptake by phosphorus-limited cells ofCorynebacterium bovis grown in batch culture and in a chemostat was measured with [(32)P] orthophosphate. It was dependent on the external phosphorus concentration and was inversely related to the amount of intracellular phosphorus. The relationship between the initial rate of uptake, intracellular phosphorus, and phosphorus concentration in the medium can be expressed in terms of Haldane's modification of the Michaelis-Menten equation. PMID- 24241028 TI - Restricted pH ranges and reduced yields for bacterial growth under pressure. AB - Hydrostatic pressure was found to cause a marked narrowing of pH ranges for growth and reductions in growth yields for a variety of bacteria. In many cases, reduced yields under pressure could be directly related to increased sensitivities to metabolic acids that accumulated in the enclosed culture vessels used. Magnesium and calcium ions partially reversed increases in sensitivities of representative gram-positive and gram-negative bacteria to low, but not high, pH. Growth inhibition of these organisms at both extremes of pH was associated with enhanced loss of K(+) from pressurized cells. Inhibited cells in alkaline media also lysed under pressure, but microscopically observable lysis was clearly a secondary phenomenon because it occurred slowly. Apparent volumes for growth inhibitory protonation-deprotonation reactions were calculated on the basis of measured shifts in inhibitory pH with pressure. The values ranged from 99 to 431 ml/mole, and their magnitudes indicated that growth inhibition by acids or bases involves cooperative changes in polymeric interactions such as those which accompany protein denaturation. PMID- 24241029 TI - The ecology of mercury-resistant bacteria in Chesapeake Bay. AB - Total ambient mercury concentrations and numbers of mercury resistant, aerobic heterotrophic bacteria at six locations in Chesapeake Bay were monitored over a 17 month period. Mercury resistance expressed as the proportion of the total, viable, aerobic, heterotrophic bacterial population reached a reproducible maximum in spring and was positively correlated with dissolved oxygen concentration and sediment mercury concentration and negatively correlated with water turbidity. A relationship between mercury resistance and metabolic capability for reduction of mercuric ion to the metallic state was established by surveying a number of HgCl2-resistant cultures. The reaction was also observed in microrganisms isolated by differential centrifugation of water and sediment samples. Mercuric ion exhibited an average half-life of 12.5 days in the presence of approximately 10(5) organisms/ml. Cultures resistant to 6 ppm of mercuric chloride and 3 ppm of phenylmercuric acetate (PMA) were classified into eight generic categories.Pseudomonas spp. were the most numerous of those bacteria capable of metabolizing both compounds; however, PMA was more toxic and was more selective forPseudomonas. The mercury-resistant generic distribution was distinct from that of the total bacterial generic distribution and differed significantly between water and sediment, positionally and seasonally. The proportion of nonglucose-utilizing mercury-resistantPsuedomonas spp. was found to be positively correlated with total bacterial mercury resistance. It is concluded from this study that numbers of mercury-resistant bacteria as established by plate count can serve as a valid index ofin situ Hg(2+) metabolism. PMID- 24241030 TI - Optimization of procedures for the recovery of heterotrophic bacteria from marine sediments. AB - A study was undertaken of the various factors affecting the recovery of heterotrophic bacteria from marine sediments. The dilution medium and culture medium were found to be of great importance in the recovery of heterotrophic colony forming units (CFU). Statistical analysis of the total viable counts obtained under the test conditions showed that artificial seawater (ASW) without further supplementation was equal to or superior to ASW plus 0.1% peptone or ASW plus 0.1% peptone and 0.1% glycerol. The addition of a surfactive agent, on the other hand, resulted in 95% inhibition of the recoverable CFU. The elapsed time (up to 12 hr) between recovery of a sedimentary core and completion of plating procedures was found to have little effect provided the sedimentary sample was removed from the core, placed in ASW, and stored in a refrigerator until actual plating occurred. It was further noted that lower organic nutrient concentrations, approximately one-tenth of those generally in use, resulted in significantly higher total viable counts. Finally, replicate contiguous sampling at three depths in a core resulted in no significant changes in the number of CFU from the surface samples, indicating a greater surface homogeneity than that previously suspected. The same pattern was not true, however, for samples obtained a lower positions in the core, thus indicating pockets of microbial concentration. PMID- 24241031 TI - Influence of clay minerals on sorption of bacteriolytic enzymes. AB - Myxobacteria presumably produce extracellular bacteriolytic enzymes when they are growing in soil. In order to study their ecological significance, adsorption experiments were performed with lytic enzymes produced byMyxococcus virescens in casitone media. Different soils as well as montmorillonite and kaolinite can rapidly adsorb the bacteriolytic but not the proteolytic enzymes. About 1 gm of montmorillonite per liter of cell-free culture solution is enough for the adsorption of 97% of the bacteriolytic enzymes. The adsorption per unit weight is about 100 times greater on montmorillonite than on kaolinite. About 40% of the adsorbed enzymes can be eluted with solutions of high pH or high ionic strength. The only desorbed bacteriolytic enzyme is the alanyl-?-N-lysine endopeptidase. PMID- 24241032 TI - Chemosensory responses by the heterotrophic marine dinoflagellateCrypthecodinium cohnii. AB - Chemosensory responses by the colorles inshore marine dinoflagellateCrypthecodinium cohnii were observed in quadrant-divided Petri plates containing an agar layer + liquid overlay. A suspension of organisms in salt solution was poured onto this and allowed to stand 3 hr. A differential tendency of the cells to become firmly attached or embedded in the substratum was observed when various substances were incorporated in the gel. A positive response (tendency to attach) occurred with: alpha-L-fucose, dimethyl-beta propiothetin, betaine, sucrose, glycine, L-alanine, hemin, and fructose; negative response: formalin, glutathione, acid hydrolyzed agar, protamine SO4, L-glutamic acid, lactose, glutamine, taurine, L-aspartic acid, putrescine 2 HCl, choline citrate, choline bitartrate, K citrate, and choline HCl. gamma-Aminobutyric acid was negative or positive dependeng on concentration. Dead or immotile cells did not become attached. The following compounds elicited no response: alpha-D fucose, dimethyl acetothetin chloride, cyclic AMP, and glucose. PMID- 24241033 TI - Work disability and state benefit claims in early rheumatoid arthritis: the ERAN cohort. AB - OBJECTIVE: RA is an important cause of work disability. This study aimed to identify predictive factors for work disability and state benefit claims in a cohort with early RA. METHODS: The Early RA Network (ERAN) inception cohort recruited from 22 centres. At baseline, and during each annual visit, participants (n = 1235) reported employment status and benefits claims and how both were influenced by RA. Survival analysis derived adjusted hazard ratios (aHRs) and 95% CIs to predict associations between baseline factors and time until loss of employment due to RA or a state benefits claim due to RA. RESULTS: At baseline, 47% of participants were employed and 17% reported claiming benefits due to RA. During follow-up, loss of employment due to RA was reported by 10% (49/475) of the participants and 20% (179/905) began to claim benefits. Independent predictors of earlier work disability were bodily pain (aHR 2.45, 95% CI 1.47, 4.08, P = 0.001) and low vitality (aHR 1.84, 95% CI 1.18, 2.85, P = 0.007). Disability (aHR 1.28, 95% CI 1.02, 1.61, P = 0.033), DAS28 (aHR 1.48, 95% CI 1.05, 2.09, P = 0.026) and extra-articular disease (aHR 1.77, 95% CI 1.17, 2.70, P = 0.007) predicted earlier benefits claims. CONCLUSION: Work disability and benefits claims due to RA were predicted by different baseline factors. Pain and low vitality predicted work disability. Baseline disability, extra-articular disease manifestations and disease activity predicted new benefits claims due to RA. Future research on interventions targeting these factors could investigate job retention and financial independence. PMID- 24241034 TI - alpha9beta1 integrin acts as a critical intrinsic regulator of human rheumatoid arthritis. AB - OBJECTIVE: The role of the joint tissue microenvironment in the pathogenesis of human RA has recently attracted much attention. The present study investigated the roles of alpha9beta1 integrin and its ligands in synovial specimens of human RA patients in generating the unique human arthritic tissue microenvironment. METHODS: Synovial fibroblasts and macrophages were isolated from the synovial tissue of patients with RA or OA. The expression of alpha9beta1 integrin was analysed using FACS with multicolour staining. The production of MMPs and proinflammatory cytokines was analysed in cultures of synovial fibroblasts and macrophages with alpha9beta1 integrin ligands. RESULTS: Synovial fibroblasts and macrophages derived from arthritic joints spontaneously secreted tenascin-C and osteopontin. Synovial fibroblasts and macrophages obtained from patients with RA expressed alpha9beta1 integrins, a common receptor for osteopontin and tenascin C. In the synovial fibroblasts of RA, the amount of tenascin-C protein produced was much greater than that of osteopontin in synovial fibroblasts of RA. Importantly, autocrine and paracrine interactions of alpha9beta1 integrin and tenascin-C induced the expression of MMPs and IL-6 in synovial fibroblasts, as well as TNF-alpha and IL-1beta in synovial macrophages. CONCLUSION: These findings indicate that autocrine and paracrine interaction of alpha9beta1 integrin and tenascin-C in the joint tissue microenvironment contributes to the pathogenesis of RA. Therefore alpha9beta1 integrin may become a potential therapeutic target for RA. PMID- 24241035 TI - Physician global assessment at 3 months is strongly predictive of remission at 12 months in early rheumatoid arthritis: results from the CATCH cohort. AB - OBJECTIVE: The objective of this study was to determine predictors of 1-year remission in early RA (ERA) using baseline and 3-month data. METHODS: The Canadian Early Arthritis Cohort (CATCH) patients were included if baseline, 3- and 12-month data were available. Regression analyses for four different definitions of remission at 12 months were done to determine baseline and 3-month predictors of remission. RESULTS: Five hundred and sixty-two patients had complete data at 12 months (mean age 53.4 years, disease duration 6.2 years, 73% female). The factors at baseline associated with all four remission outcomes at 12 months were age, gender, income, education, tender joint count (TJC), patient global assessment (PtGA), HAQ and pain. Baseline ESR was associated with the 28 joint DAS (DAS28) remission only. At 3 months, all four remission definitions were associated with TJC, swollen joint count, physician global assessment (PGA), PtGA, HAQ, pain, ESR and CRP in univariate analyses. In the regression model, variables associated with Simple Disease Activity Index remission were PGA [odds ratio (OR) 0.77, P < 0.001), pain (OR 0.85, P = 0.004), age (OR 0.98, P = 0.006) and HAQ (OR 0.49, P = 0.011); Clinical Disease Activity Index remission was associated with PGA (OR 0.77, P < 0.001), pain (OR 0.85, P = 0.003), age (OR 0.98, P = 0.015) and CRP (OR 0.80, P = 0.031). DAS28 remission was predicted by ESR (OR 0.95, P < 0.001), PGA (OR 0.76, P < 0.001), age (OR 0.98, P = 0.001), HAQ (OR 0.57, P = 0.006) and male gender (OR 2.01, P = 0.005), whereas Boolean remission was associated with pain (OR 0.79, P = 0.009), age (OR 0.98, P = 0.016), PtGA (OR 0.83, P = 0.025) and PGA (OR 0.86, P = 0.038). CONCLUSION: A low PGA at 3 months was consistently associated with 1-year remission in ERA. PMID- 24241036 TI - Cardiac arrhythmias and conduction defects in systemic sclerosis. AB - Signs and symptoms of arrhythmias or conduction defects are frequently reported in patients with SSc. These rhythm disorders may have several origins (i.e., related to primary heart involvement, pericardial disease, valvular regurgitation or pulmonary arterial hypertension) and may negatively affect the overall prognosis of these patients. It is therefore important to identify patients at high risk for cardiac arrhythmias with a complete cardiological evaluation and to identify the underlying heart disease, including SSc-related myocardial involvement. In addition, some therapeutic options in SSc patients may differ from those recommended in other populations. PMID- 24241037 TI - Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats. AB - OBJECTIVE: Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. METHODS: Male Wistar rats (180-200 g) were used for the complete Freund's adjuvant (CFA) induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. RESULTS: Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CONCLUSION: CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA. PMID- 24241038 TI - IgG4-related orbital tumour with eye enucleation--infra-orbital nerve enlargement. PMID- 24241039 TI - Plasmolysis of Pteridium protoplasts: A study using light and scanning-electron microscopy. AB - A study was undertaken using gametophytes of the fern Pteridium aquilinum to examine the effects of plasmolysis on the topography of protoplasts. Methods are described whereby the surfaces of non-isolated protoplasts can be observed in the plasmolysed condition using scanning electron microscopy. Plasmolysed gametophytes were also examined in the light microscope using differential interference contrast and ultra-violet fluorescence microscopy after staining with fluorescein diacetate. With scanning electron microscopy, plasmolysed protoplast surfaces appeared smooth with no evidence of wrinkling or infolding of excess membrane. The formation of irregular-shaped protoplasts, protoplasmic threads, subprotoplasts, and protoplasmic networks covering internal wall surfaces all provided evidence for strong wall adhesion of the protoplasm. The availability of membrane for uptake into folds or vesicles is therefore thought to be minimal. Transmission electron microscopy showed some protoplasmic threads to be plasmodesmata, the remainder being cell-wall contact points. Remnants of these threads were occasionally observed on isolated protoplasts in both the light and electron microscopes. PMID- 24241040 TI - The developmental morphology and growth dynamics of the tobacco leaf. AB - The developmental morphology and growth dynamics of the leaf of Nicotiana tabacum L. cv. Xanthi Nc. are described. Epidermal and internal cell patterns indicate that the leaf axis arises from approx. 100 cells in four layers of the shoot apex, while the lamina arises from several rows of cells in each of three layers of the leaf axis. Cell patterns at the apex and margin of the leaf do not support the classical view that these regions have a specialized meristematic function. Instead the development of the leaf appears to be largely dependent on intercalary growth. The pattern of growth within the lamina is surprisingly complex. In addition to a proximal-distal gradient in the duration of growth and cell division during development, localized transitory changes in the rate of these processes also occur. These observations are discussed in reference to previous discriptions of leaf development in tobacco. PMID- 24241041 TI - The cellular parameters of leaf development in tobacco: a clonal analysis. AB - The cellular parameters of leaf development in tobacco (Nicotiana tabacum L.) have been characterized using clonal analysis, an approach that provides unequivocal evidence of cell lineage. Our results indicate that the tobacco leaf arises from a group of around 100 cells in the shoot apical meristem. Each of these cells contributes to a unique longitudinal section of the axis and transverse section of the lamina. This pattern of cell lincage indicates that primordial cells contribute more or less equally to the growth of the axis, in contrast to the more traditional view of leaf development in which the leaf is pictured as arising from a group of apical initials. Clones induced prior to the initiation of the lamina demonstrate that the subepidermal layer of the lamina arises from at least six files of cells. Submarginal cells usually divide with their spindles parallel to the margin, and therefore contribute relatively little to the transverse expansion of the lamina. During the expansion of the lamina the orientation and frequency of cell division are highly regulated, as is the duration of meristematic growth. Initially, cell division is polarized so as to produce lineages that are at an oblique angle to the midrib; later cell division is in alternating perpendicular planes. The distribution of clones generated by irradiation at various stages of development indicates that cell division ceases at the tip of the leaf when the leaf is about one tenth its final size, and then ceases in progressively more basal regions of the lamina. Variation in the mutation frequency within the lamina reflects variation in the frequency of mitosis. Prior to the mergence of the leaf the frequency of mutation is maximal near the tip of the leaf and extremely low at its base; after emergence, the frequency of mutation increases at the base of the leaf. In any given region of the lamina the frequency of mutation is highest in interveinal regions, and is relatively low near the margin. Thus, both the orientation and frequency of cell division at the leaf margin indicate that this region plays a minor role in the growth of the lamina. PMID- 24241042 TI - Plasmatubules: fact or artefact? AB - Plasmatubules are tubular evaginations of the plasmalemma associated with sites where high solute flux occurs between apoplast and symplast. Plasmatubules of the scutellar epithelial cells of germinating barley (Hordeum vulgare L.) have been examined following a variety of fixation methods. Of the aqueous fixations, primary aldehyde fixation with osmium post-fixation and osmium as the primary fixative gave comparable images, whilst potassium permanganate resulted in some distortion of the tissue in general including dilation of the tubular evaginations of the plasmalemma. Freeze-fixation and substitution with acetone and acetone-osmium gave images of the plasmalemma comparable to those obtained by the aqueous aldehyde and osmium methods. The similarity of structure with aldehyde or osmium and freezing as the primary fixation is taken to indicate that plasmatubules are real and not artefacts resulting from the fixation procedure. PMID- 24241043 TI - Plasmatubules in transfer cells of pea (Pisum sativum L.). AB - Plasmatubules are tubular evaginations of the plasmalemma. They have previously been found at sites where high solute flux between apoplast and symplast occurs for a short period and where wall proliferations of the transfer cell type have not been developed (Harris et al. 1982, Planta 156, 461-465). In this paper we describe the distribution of plasmatubules in transfer cells of the leaf minor veins of Pisum sativum L. Transfer cells are found in these veins associated both with phloem sieve elements and with xylem vessels. Plasmatubules were found, in both types of transfer cell and it is suggested that the specific distribution of the plasmatubules may reflect further membrane amplification within the transfer cell for uptake of solute from apoplast into symplast. PMID- 24241044 TI - Plastid changes during the conversion of chloroplasts to chromoplasts in ripening tomatoes. AB - Methods were developed for the isolation of plastids from mature green and ripening tomatoes (Lycopersicon esculentum Mill.) and purification by sucrose or Percoll density-gradient centrifugation. Assessment of the purity of preparations involved phase-contrast and electron microscopy, assays for marker enzymes and RNA extraction and analysis. Proteins were extracted from isolated plastids at different ripening stages and separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The profiles obtained from chloroplasts and chromoplasts showed many qualitative and quantitative differences. Labelling of proteins with [(35)S]methionine in vivo showed that there was active protein synthesis throughout ripening, but there was a change in the plastid proteins made as ripening proceeded. The cellular location of synthesis of specific proteins has yet to be established. PMID- 24241045 TI - Fusion characteristics of plant protoplasts in electric fields. AB - The electrical parameters important in the fusion of plant protoplasts aligned dielectrophoretically in high-frequency alternating electric fields have been established. Protoplasts were aligned in an alternating electric field between two relatively distant (1 mm) electrodes, by dielectrophoresis induced by field inhomogeneities caused by the protoplasts themselves. This arrangement allowed ease of manipulations, large throughput and low loss of protoplasts. In analytical experiments, sufficiently large samples could be used to study pulse duration-fusion response relations at different pulse voltages for protoplasts of different species, tissues and size (mesophyll protoplasts of Solanum brevidens, Triticum aestivum, Hordeum vulgare; suspension-culture protoplasts of Nicotiana sylvestris, N. rustica, Datura innoxia and S. brevidens; root-tip protoplasts of Vicia faba, hypocotyl protoplasts of Brassica napus). The percentage of aligned protoplasts that fused increased with increasing pulse parameters (pulse duration; voltage) above a threshold that was dependant on pulse voltage. The maximum fusion values obtained depended on a number of factors including protoplast origin, size and chain length. Leaf mesophyll protoplasts fused much more readily than suspension-culture protoplasts. For both types, there was a correlation of size with fusion yield: large protoplasts tended to fuse more readily than small protoplasts. In short chains (?five protoplasts), fusion frequency was lower, but the proportion of one-to-one products was greater than in long chains (?ten protoplasts). In formation by electrofusion of heterokaryons between mesophyll and suspension-culture protoplasts, the fusion-frequency response curves reflected those of homofusion of mesophyll protoplasts rather than suspension-culture protoplasts. There was no apparent limitation to the fusion of the smallest mesophyll protoplast with the largest suspension-culture protoplasts. Based on these observations, it is possible to direct fusion towards a higher frequency of one-to-one (mesophyll/suspension) products by incorporating low densities of mesophyll protoplasts in high densities of suspensionculture protoplasts and by using a short fusion pulse. The viability of fusion products, assessed by staining with fluorescein diacetate, was not impaired by standard fusion conditions. On a preparative scale, heterokaryons (S. brevidens mesophyll N. sylvestris or D. innoxia suspension-culture) were produced by electrofusion and cultured in liquid or embedded in agar, and were capable of wall formation, division and growth. It is concluded that the electrode arrangement described is more suitable for carrying out directed fusions of plant protoplasts than that employing closer electrodes. PMID- 24241046 TI - Electrical fusion for optimal formation of protoplast heterokaryons in Nicotiana. AB - The electrical fusion of protoplasts has been studied in order to maximize the formation of heterokaryons for culture. Heterokaryons of Nicotiana tabacum L. mesophyll protoplasts and N. plumbaginifolia Viviani supension-cell protoplasts were identified in fixed and stained as well as living material; a quantitative fusion index was thereby developed. With this index the efficiencies of various electric fields and fusion-chamber designs have been determined. Optimal fusion was obtained with an alternating-current (AC) field of 150 V/cm and direct current (DC) square-wave pulses of 1000 V/cm. A new, simple-to-use, largescale fusion chamber is described in which batches of up to 5.10(5) protoplasts (0.5 ml of cells at 10(6)/ml) can be fused in 5-7 min with efficiencies approaching 40%. Half of the fusion products are heterokaryons, thus fusion is random. Of the fusion products, 60% are bi- or trinucleate. Using fusion procedures similar to those described here Bates and C. Hasenkampf (1985, Theor. Appl. Genet., in press) have recovered viable somatic hybrids which have been regenerated. PMID- 24241047 TI - Observations on enzymatically isolated, living and fixed embryo sacs in several angiosperm species. AB - A technique has been developed for isolating embryo sacs (ESs) by enzymatic maceration. Ovules were macerated in a mixture of pectinase, cellulase and, in some cases, snailase and pectolyase Y-23. The ovular tissues were removed and the ESs were isolated in toto. Embryo sacs were isolated from both fixed and fresh ovules of Antirrhinum majus L., Helianthus annuus L. and Nicotiana tabacum L. Fluorochromasia by fluorescein diacetate showed that the ESs isolated from fresh ovules were viable. The method has promise for various histochemical and cell physiological studies and quite possibly also for in-vitro culture of ESs. PMID- 24241048 TI - Gas chromatography-mass spectrometry evidence for several endogenous auxins in pea seedling organs. AB - Qualitative analysis by gas chromatography-mass spectrometry (GC-MS) of the auxins present in the root, cotyledons and epicotyl of 3-dold etiolated pea (Pisum sativum L., cv. Alaska) seedlings has shown that all three organs contain phenylacetic acid (PAA), 3-indoleacetic acid (IAA) and 4-chloro-3-indoleacetic acid (4Cl-IAA). In addition, 3-indolepropionic acid (IPA) was present in the root and 3-indolebutyric acid (IBA) was detected in both root and epicotyl. Phenylacetic acid, IAA and IPA were measured quantitatively in the three organs by GC-MS-single ion monitoring, using deuterated internal standards. Levels of IAA were found to range from 13 to 115 pmol g(-1) FW, while amounts of PAA were considerably higher (347-451 pmol g(-1) FW) and the level of IPA was quite low (5 pmol g(-1) FW). On a molar basis the PAA:IAA ratio in the whole seedling was approx. 15:1. PMID- 24241049 TI - The effects of salinity on ion concentrations within the root cells of Zea mays L. AB - Zea mays is a salt-sensitive crop species which in saline (?100 mol m(-3) NaCl) conditions suffers considerable growth reduction correlated with elevated Na(+) and Cl(-) concentration within the leaves. To increase understanding of the regulation of ion uptake and transport by the roots in saline conditions, ion concentrations within individual root cortical cells were determined by X-ray microanalysis. There was variation in Na(+), K(+) and Cl(-) distributions among individual cells, which could not be correlated with their spatial position in the roots. Generally, however, in response to saline growth conditions (100 mol m(3) NaCl) Na(+) and Cl(-) were mostly localized in the vacuoles, although their concentrations were also sometimes increased in the cytoplasm and cell walls. The concentration of K(+) in the cytoplasm was usually maintained at a level (mean 79 mol m(-3)) compatible with the biochemical functions ascribed to this ion. PMID- 24241050 TI - Interactive effects of light, leaf temperature, CO2 and O 2 on photosynthesis in soybean. AB - A biochemical model of C 3photosynthesis has been developed by G.D. Farquhar et al. (1980, Planta 149, 78-90) based on Michaelis-Menten kinetics of ribulose-1,5 bisphosphate (RuBP) carboxylase-oxygenase, with a potential RuBP limitation imposed via the Calvin cycle and rates of electron transport. The model presented here is slightly modified so that parameters may be estimated from whole-leaf gas exchange measurements. Carbon-dioxide response curves of net photosynthesis obtained using soybean plants (Glycine max (L.) Merr.) at four partial pressures of oxygen and five leaf temperatures are presented, and a method for estimating the kinetic parameters of RuBP carboxylase-oxygenase, as manifested in vivo, is discussed. The kinetic parameters so obtained compare well with kinetic parameters obtained in vitro, and the model fits to the measured data give r (2)values ranging from 0.87 to 0.98. In addition, equations developed by J.D. Tenhunen et al. (1976, Oecologia 26, 89-100, 101-109) to describe the light and temperature responses of measured CO2-saturated photosynthetic rates are applied to data collected on soybean. Combining these equations with those describing the kinetics of RuBP carboxylase-oxygenase allows one to model successfully the interactive effects of incident irradiance, leaf temperature, CO2 and O2 on whole leaf photosynthesis. This analytical model may become a useful tool for plant ecologists interested in comparing photosynthetic responses of different C3 plants or of a single species grown in contrasting environments. PMID- 24241051 TI - Induction of phenoloxidase in cell suspension cultures of Mucuna pruriens L. : Effects on accumulation of L-3,4-dihydroxyphenylalanine and biotransformation capacity. AB - The effects of limitating nitrogen-containing compounds in the medium and of adding the amino-acid analogues p-fluorophenylalanine and ethionine on both phenoloxidase activity and the accumulation of L-3,4-dihydroxyphenylalanine (L DOPA) are reported for cell suspension cultures of Mucuna pruriens. Nitrogen limitation of the cultures, or the addition of p-fluorophenylalanine or ethionine to the culture medium resulted in an increased phenoloxidase activity. There appeared to be an inverse relationship between phenoloxidase activity and the acccumulation of L-tyrosine into L-DOPA by alginate-entrapped cells occurred at a higher rate when phenoloxidase activity was increased. PMID- 24241052 TI - The immobility of pectic substances in injured tomato leaves and its bearing on the identity of the wound hormone. AB - It has been suggested that pectic polysaccharides (or oligosaccharides cleaved from them) are liberated from the cell wall upon wounding of leaf tissue, and that they act as long-distance hormones evoking a defence response in neighbouring uninjured leaves (P.D. bishop et al. 1981, Proc. Natl. Acad. Sci. USA 78, 3536-3540, and cited literature). We have tested this hypothesis by infiltration of radioactive pectic fragments (rhamnogalacturonans and homogalacturonans of degrec of polymerisation down to 6) into wounds on tomato leaves. No radioactivity was exported from the treated leaf. [(14)C]Sucrose, applied in the same way, was effectively translocated, probably via the phloem. We suggest that pectic substances are not themselves long-distance wound hormones. The possibility remains that pectic substances, solubilised on wounding, act in the immediate vicinity of the wound to stimulate the dispatch of a second messenger, which would be the long-distance wound hormone. PMID- 24241053 TI - Some effects of 4-chloro-5-(dimethylamino)-2-phenyl-3(2H)-pyridazinone (San 9785) on the development of chloroplast thylakoid membranes in Hordeum vulgare L. AB - Chloroplast ultrastructural and photochemical features were examined in 6-d-old barley (Hordeum vulgare L. cv. Sundance) plants which had developed in the presence of 4-chloro-5-(dimethylamino)-2-phenyl-3(2H)-pyridazinone (San 9785). In spite of a substantial modification of the fatty-acid composition of thylakoid lipids there were no gross abnormalities in chloroplast morphology, and normal amounts of membrane and chlorophyll were present. Fluorescence kinetics at 77K demonstrated considerable energetic interaction of photosystem (PS)I and PSII chlorophylls within the altered lipid environment. An interference with electron transport was indicated from altered room-temperature fluorescence kinetics at 20 degrees C. Subtle changes in the arrangements of chloroplast membranes were consistently evident and the overall effects of these changes was to increase the proportion of appressed to nonappressed membranes. This correlated with a lower chlorophyll a/b ratio, an increase in the amount of light-harvesting chlorophylls as determined by gel electrophoresis and fluorescence emission spectra, and an increase in excitation-energy transfer from PSII to PSI, as predicted from current ideas on the organisation of photosystems in appressed and non-appressed thylakoid membranes. PMID- 24241054 TI - Enzymatic reduction of (+)-dihydroflavonols to flavan-3,4-cis-diols with flower extracts from Matthiola incana and its role in anthocyanin biosynthesis. AB - A cell-free extract from flowers of Matthiola incana catalyzes a NADPH-dependent stereospecific reduction of (+)-dihydrokaempferol to 3,4-cis-leucopelargonidin (5,7,4'-trihydroxyflavan-3,4-cis-diol). The pH-optimum of this reaction is around 6. The rate of reaction with NADH was about 50% of that found with NADPH. (+) Dihydroquercetin and (+)-dihydromyricetin were also reduced by the enzyme preparation to the corresponding flavan-3,4-cis-diols. Correlation between the genotype of M. incana and the presence of dihydroflavonol 4-reductase is strong evidence that this enzyme is involved in anthocyanin biosynthesis. PMID- 24241055 TI - Occurrence of two cell subpopulations with different cell-cycle durations in the central and peripheral zones of the vegetative shoot apex of Sinapis alba L. AB - The cell-cycle duration and the growth fraction were estimated in the vegetative shoot apical meristem of Sinapis alba L. The length of the cell cycle was about 86 h, i.e. 2.5 times shorter than the cell-doubling time (M. Bodson, 1975, Ann. Bot. 39, 547-554) and the growth fraction was between 32 to 41%. These data demonstrated that the cell population of this meristem was heterogeneous, including one subpopulation of rapidly cycling cells and one subpopulation of non cycling cells, i.e. cells with a very long cell cycle compared with that of the rapidly cycling cells. Non-cycling cells had no particular localization within the meristem. Both the central and peripheral zones of the meristem were mosaics of rapidly cycling and non-cycling cells. PMID- 24241056 TI - Promotion of flowering in apple trees with gibberellin A4 and C-3 epi-gibberellin A 4. AB - The proportion of spurs flowering on apple trees (Malus domestica Borkh. cv Golden Delicious) displaying a high degree of alternate-year flowering was increased in the "off" year by gibberellin A4 (GA4) and C-3 epi-GA4 applied in the previous year. When applied 4.5 weeks after anthesis amounts of GA4 ranging from 3 to 300 MUg per spur and 25 or 50 MUg of C-3 epi-GA4 per spur were effective. Treatments with GA4 made seven weeks after anthesis were less effective. A combination of 30 MUg GA4 and 30 MUg zeatin (6-(4-hydroxy-3 methylbut-trans-2-enylamino)purine) promoted flowering at both treatment times, and tended to be more effective than GA4 alone. PMID- 24241057 TI - Dynamic resistant hypertension patterns as predictors of cardiovascular morbidity: a 4-year prospective study. AB - OBJECTIVE: Little is known regarding the clinical course and prognosis of resistant hypertension (RHT). We evaluated predictors of persistent RHT and the associated cardiovascular risk. METHODS: We studied 1911 treated hypertensive patients (aged 59+/-11 years, 49% men) for a mean period of 3.9 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT (office-based uncontrolled hypertension under at least three drugs including a diuretic or controlled hypertension under four or more drugs). Endpoint of interest was the composite of coronary artery disease and stroke. MAIN RESULTS: Four groups were identified depending on presence or absence of RHT at baseline and follow-up: 1153 patients (60%) never having RHT, 189 (10%) with resolved RHT, 204 (11%) with incident RHT and 365 (19%) with persistent RHT. Two-thirds of the patients with RHT at baseline remained resistant at the end of the study. Independent variables associated with both incident and persistent RHT were diabetes mellitus, history of cardiovascular disease, hypertension duration, SBP, left ventricular hypertrophy and glomerular filtration rate. Persistent RHT compared with never-having RHT was associated with a 2.2-fold increased risk for cardiovascular morbidity (95% CI: 1.21-4.05, P = 0.01) after adjustment for risk factors. CONCLUSION: In treated hypertensive patients, among prospective RHT dynamic patterns, persistent RHT is frequent and independently associated with adverse cardiovascular prognosis. PMID- 24241058 TI - Enhanced activation of NAD(P)H: quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5'-monophosphate-activated protein kinase-mediated guanosine 5'-triphosphate cyclohydrolase 1 preservation. AB - AIMS: Guanosine 5'-triphosphate cyclohydrolase-1 (GTPCH-1) is a rate-limiting enzyme in de-novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS) coupling. Adenosine 5'-monophosphate activated protein kinase (AMPK) is crucial for GTPCH-1 preservation, and tumor suppressor kinase liver kinase B1 (LKB1), an upstream kinase of AMPK, is activated by NAD-dependent class III histone deacetylase sirtuin 1 (SIRT1) mediated deacetylation. beta-Lapachone has been shown to increase cellular NAD/NADH ratio via NAD(P)H: quinone oxidoreductase 1 (NQO1) activation. In this study, we have evaluated whether beta-lapachone-induced NQO1 activation modulates blood pressure (BP) through preservation of GTPCH-1 in a hypertensive animal model. METHODS AND RESULTS: Spontaneously hypertensive rats (SHRs), primary aortic endothelial cells, and endothelial cell line were used to investigate the hypotensive effect of beta-lapachone and its action mechanism. beta-Lapachone treatment dramatically lowered BP and vascular tension in SHRs and induced eNOS activation in endothelial cells. Consistent with these effects, beta-lapachone treatment also elevated levels of both aortic cGMP and plasma nitric oxide in SHRs. Meanwhile, beta-lapachone-treated SHRs showed significantly increased levels of aortic NAD, LKB1 deacetylation, and AMPK Thr phosphorylation followed by increased GTPCH-1 and tetrahydrobiopterin/dihydrobiopterin ratio. In-vitro study revealed that AMPK inhibition by overexpression of dominant-negative AMPK nearly abolished GTPCH-1 protein conservation. Enhanced LKB1 deacetylation and AMPK activation were also elicited by beta-lapachone in endothelial cells. However, inhibition of LKB1 deacetylation by blocking of NQO1 or SIRT1 blunted AMPK activation by beta-lapachone. CONCLUSION: This is the first study demonstrating that eNOS coupling can be regulated by NQO1 activation via LKB1/AMPK/GTPCH-1 modulation, which is possibly correlated with relieving hypertension. These findings provide strong evidence to suggest that NQO1 might be a new therapeutic target for hypertension. PMID- 24241059 TI - Integrative biology of tail autotomy in lizards. AB - Self-amputation (autotomy) of the tail is essential for the survival of many lizards. Accordingly, it has garnered the attention of scientists for more than 200 years. Several factors can influence the release of the tail, such as the size, sex, and age of the lizard; type of predator; ecology; and evolutionary history of the lineage. Once lost, the tail will writhe for seconds to minutes, and these movements likely depend on the size and physiology of the tail, habitat of the lizard, and predation pressure. Loss of the tail will, in turn, have impacts on the lizard, such as modified locomotor performance and mechanics, as well as escape behavior. However, the tail is almost always regenerated, and this involves wound healing, altered investment of resources, and tissue differentiation. The regenerated tail generally differs from the original in several ways, including size, shape, and function. Here we summarize recent findings of research pertaining to tail autotomy, and we propose a framework for future investigations. PMID- 24241060 TI - Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails. AB - The ability to shed an appendage occurs in both vertebrates and invertebrates, often as a tactic to avoid predation. The tails of lizards, unlike most autotomized body parts of animals, exhibit complex and vigorous movements once disconnected from the body. Despite the near ubiquity of autotomy across groups of lizards and the fact that this is an extraordinary event involving the self severing of the spinal cord, our understanding of why and how tails move as they do following autotomy is sparse. We herein explore the histochemistry and physiology of the tail muscles of the leopard gecko (Eublepharis macularius), a species that exhibits vigorous and variable tail movements following autotomy. To confirm that the previously studied tail movements of this species are generally representative of geckos and therefore suitable for in-depth muscle studies, we quantified the three-dimensional kinematics of autotomized tails in three additional species. The movements of the tails of all species were generally similar and included jumps, flips, and swings. Our preliminary analyses suggest that some species of gecko exhibit short but high-frequency movements, whereas others exhibit larger-amplitude but lower-frequency movements. We then compared the ATPase and oxidative capacity of muscle fibers and contractile dynamics of isolated muscle bundles from original tails, muscle from regenerate tails, and fast fibers from an upper limb muscle (iliofibularis) of the leopard gecko. Histochemical analysis revealed that more than 90% of the fibers in original and regenerate caudal muscles had high ATPase but possessed a superficial layer of fibers with low ATPase and high oxidative capacity. We found that contraction kinetics, isometric force, work, power output, and the oscillation frequency at which maximum power was generated were lowest in the original tail, followed by the regenerate tail and then the fast fibers of the iliofibularis. Muscle from the original tail exhibited greater resistance to fatigue, followed by the regenerate tail and then the fast iliofibularis fibers. These results suggest that the relatively slow and oxidative fibers found within the tail musculature have a significant impact on contractile function, which translates into a trade off between longevity of performance and power after autotomy. PMID- 24241061 TI - The anatomy and histology of caudal autotomy and regeneration in lizards. AB - Abstract Caudal autotomy-the ability to self-detach the tail-is a dramatic adaptation common to many structural-grade lizards. For most species, tail loss is followed by the equally dramatic phenomenon of tail regeneration. Here we review the anatomy and histology of caudal autotomy and regeneration in lizards, drawing heavily from research published over the past 2 decades. The autotomous tail is characterized by various structural adaptations, which act to minimize blood loss and trauma to adjacent tissues. The early phase of wound healing involves a leukocytic response but limited inflammation. Reepithelialization via a specialized wound epithelium is not only critical for scar-free healing but also necessary for subsequent tissue patterning and regenerative outgrowth. Regeneration begins with the formation of the blastema, a mass of proliferating mesenchymal-like cells. As the blastema expands, it is invaded by blood vessels and the spinal cord. Whereas the replacement tail outwardly resembles the original appendage, it differs in several notable respects, including the tissue composition and organization of the skeleton, muscular system, and spinal cord. Increasingly, the lizard tail is being recognized among biomedical scientists as an important model for the study of wound healing and multitissue restoration. PMID- 24241062 TI - Telling tails: selective pressures acting on investment in lizard tails. AB - Caudal autotomy is a common defense mechanism in lizards, where the animal may lose part or all of its tail to escape entrapment. Lizards show an immense variety in the degree of investment in a tail (i.e., length) across species, with tails of some species up to three or four times body length (snout-vent length [SVL]). Additionally, body size and form also vary dramatically, including variation in leg development and robustness and length of the body and tail. Autotomy is therefore likely to have fundamentally different effects on the overall body form and function in different species, which may be reflected directly in the incidence of lost/regenerating tails within populations or, over a longer period, in terms of relative tail length for different species. We recorded data (literature, museum specimens, field data) for relative tail length (n=350 species) and the incidence of lost/regenerating tails (n=246 species). We compared these (taking phylogeny into account) with intrinsic factors that have been proposed to influence selective pressures acting on caudal autotomy, including body form (robustness, body length, leg development, and tail specialization) and ecology (foraging behavior, physical and temporal niches), in an attempt to identify patterns that might reflect adaptive responses to these different factors. More gracile species have relatively longer tails (all 350 spp., P < 0.001; also significant for five of the six families tested separately), as do longer (all species, P < 0.001; Iguanidae, P < 0.05; Lacertidae, P < 0.001; Scindidae, P < 0.001), climbing (all species, P < 0.05), and diurnal (all species, P < 0.01; Pygopodidae, P < 0.01) species; geckos without specialized tails (P < 0.05); or active-foraging skinks (P < 0.05). We also found some relationships with the data for caudal autotomy, with more lost/regenerating tails for nocturnal lizards (all 246 spp., P < 0.01; Scindidae, P < 0.05), larger skinks (P < 0.05), climbing geckos (P < 0.05), or active foraging iguanids (P < 0.05). The selective advantage of investing in a relatively longer tail may be due to locomotor mechanics, although the patterns observed are also largely consistent with predictions based on predation pressure. PMID- 24241063 TI - Relative apportioning of resources to the body and regenerating tail in juvenile leopard geckos (Eublepharis macularius) maintained on different dietary rations. AB - Caudal autotomy is a widespread phenomenon among lizards, and similar processes occur in other groups of vertebrates and invertebrates. Many costs have been associated with autotomy, including the regeneration of lost biomass. For lizards, it is not known whether resources are preferentially directed toward caudal regeneration or whether regeneration occurs only when resources are abundant. Conflicting information is present in the literature, and an absence of controlled experiments prevents determination of what pattern of regeneration may occur under a given set of circumstances. We employed the leopard gecko, a fat tailed species, to examine whether tail regeneration is a priority and, if so, whether it remains so when resources become limiting. We explored this through caudal autotomy and dietary manipulation under conditions that ensured that differences in diet were sufficient to permit differential growth. We examined juvenile leopard geckos because these animals are rapidly growing and allocation of energy is not compromised by reproductive investment. The effects of dietary resource availability and the demands of caudal regeneration were compared in intact and regenerating animals. Our evidence indicates that caudal regeneration is a priority, even when resources are limiting. We conclude that tail regrowth is a priority that is associated with long-term survival and possibly reproductive success. PMID- 24241064 TI - Tail autotomy, tail size, and locomotor performance in lizards. AB - The effect of tail autotomy on locomotor performance has been studied in a number of lizard species. Most of these studies (65%) show that tail autotomy has a negative effect on sprint speed, some studies (26%) show no effect of autotomy on sprint speed, and a few (9%) show a positive effect of autotomy on sprint speed. A variety of hypotheses have been proposed to explain the variation across these studies, but none has been tested. We synthesize these data using meta-analysis and then test whether any of four variables explain the variation in how tail autotomy impacts sprint speed: (1) differences in methodology in previous studies, (2) phylogeny, (3) relative tail size, and (4) habitat use. We find little evidence that methodology or habitat use influences how sprint speed changes following tail autotomy. Although the sampling is phylogenetically sparse, phylogeny appears to play a role, with skinks and iguanids showing fairly consistent decreases in speeds after autotomy and with lacertids and geckos showing large variation in how autotomy impacts speed. After removing two outlying species with unusually large and long tails (Takydromus sp.), we find a positive relationship between relative tail size and sprint speed change after autotomy. Lizards with larger tails exhibit a greater change in speed after tail loss. This finding suggests that future studies of tail autotomy and locomotor performance might profitably incorporate variation in tail size and that species specific responses to autotomy need to be considered. PMID- 24241065 TI - The impact of tail loss on stability during jumping in green anoles (Anolis carolinensis). AB - Lizards that undergo caudal autotomy experience a variety of consequences, including decreased locomotor performance in a number of cases. One mode of locomotion common to many arboreal lizard species is jumping, and yet little is known about the effects of autotomy on this locomotor mode. In this article we review recent literature demonstrating the importance of the lizard tail as an in air stabilizer. First, we review work highlighting how a variety of lizards from diverse families can use their tails to control body position in midair. We then move on to cover recent work demonstrating how in at least one species, Anolis carolinensis, tail loss can lead to remarkable instabilities after takeoff during jumping. Such instabilities occur even when animals are jumping toward specific targets both below and above them, although individual variation in the response to tail loss is considerable. Finally, we report results from a study examining whether increased jumping experience after autotomy facilitates the recovery of in-air stability during jumping. Our work suggests it does not, at least not consistently after 5 wk, indicating that any fitness consequences associated with decreased jumping stability are likely to be long term. PMID- 24241066 TI - An experimental study of the gestation costs in a viviparous lizard: a hormonal manipulation. AB - The trade-offs between reproduction and survival or future reproduction represent the costs of reproduction, which are central to the theory of life-history traits evolution. In particular, different stages of the reproductive cycle may be associated with different costs and thus explain the evolution of alternative reproductive strategies. Viviparity (live bearing) has evolved from oviparity (egg laying) several times independently in vertebrates. To better understand these transitions, we aimed to specifically investigate gestation costs in a squamate reptile with a new experimental procedure. We reduced litter size during gestation in the common lizard (Zootoca vivipara) with a hormonal injection of arginine vasotocin. This method is less invasive than a surgical method and does not reduce the number of offspring of future reproductive events. We monitored body mass change, immune response, endurance capacity, thermoregulatory behavior, offspring characteristic at birth, female and offspring survival, female body mass gain after parturition, and offspring growth rate after birth. Maternal treatment did not significantly change the offspring characteristics measured. Thus, litter size reduction did not change offspring development during gestation. For the females, there is evidence that endurance capacity during gestation is modified because of the physical burden of the litter and because of physiological changes. With respect to gestation costs, we did not observe a trade-off between the investment during gestation and females' resources postparturition (female body mass) or survival, but there was a facultative trade off with the immune response. It will be interesting to replicate this study to increase the robustness of these results and to confirm the effects on the endurance capacity and the immune response. Gestation costs seem to be limited in this species, and they should be studied in more detail to evaluate their influence on the evolution of viviparity. PMID- 24241067 TI - Optical and physicochemical characterization of the luminous mucous secreted by the marine worm Chaetopterus sp. AB - Bioluminescence of the marine worm Chaetopterus variopedatus was first investigated several decades ago mainly using tissue extract. Light production of the worm, however, originates from a secreted mucus only. Here, we report the optical and physicochemical properties of the luminous mucus. We show that the produced light occurs as a long glow in the blue range (455 nm), which is an unusual color for a shallow benthic invertebrate. We also show that the light originates from a photoprotein whose light production is independent of molecular oxygen yet somewhat related to the physicochemical (rheological) characteristics of the mucus itself. Indeed, the mucus seems to polymerize and become more viscous on exposure to H2O2, which in turn seems to inhibit the light production. Ferrous iron was not associated with any strong stimulatory effect. This is in contrast to past studies on worm tissues showing that the light production is strongly stimulated by H2O2 and ferrous iron. Overall, our results highlight the fact that working on the luminous mucus only (vs. worm tissues) provides the ability to study its chemical properties possibly involved in the fine control of light production-as well as its rheological properties-and identify the possible interactions between these two properties. PMID- 24241068 TI - Physiological disturbances and overwinter mortality of largemouth bass from different latitudes. AB - Thermal conditions associated with winter can influence the distribution of a species. Because winter severity varies along latitudes, populations of temperate fish located along a latitudinal gradient may display variation in both sublethal and lethal responses to cold stressors. Sublethal physiological disturbances were quantified in age 1 largemouth bass (Micropterus salmoides) from populations originating from Alabama and Illinois but raised in a common environment. Fish were exposed to 6 h of rapid cold shock from 20 degrees to 8 degrees C (controls were held at 20 degrees C) and then sampled for white muscle, whole blood, and plasma. After cold shock, glucose concentrations were elevated in Alabama but not Illinois fish. Sodium was lower and chloride was higher in Alabama largemouth bass, but fish from Illinois had a greater propensity for potassium loss during cold shock. In Illinois ponds, Alabama largemouth bass exhibited lower overwinter survival (adult: 10%; age 0: 22%) than did those from Illinois (adult: 80%; age 0: 82%). Latitudinal variation in physiological responses to cold stressors may therefore influence overwinter survival of largemouth bass and the ability of a fish species to exist over large geographic areas. PMID- 24241069 TI - Interspecific differences in hypoxia-induced gill remodeling in carp. AB - The gills of many fish, but in particular those of crucian carp (Carassius carassius) and goldfish (Carassius auratus), are capable of extensive remodeling in response to changes in oxygen (O2), temperature, and exercise. In this study, we investigated the interspecific variation in hypoxia-induced gill modeling and hypoxia tolerance in 10 closely related groups of cyprinids (nine species, with two strains of Cyprinus carpio). There was significant variation in hypoxia tolerance, measured as the O2 tension (P(O2)) at which fish lost equilibrium (LOEcrit), among the 10 groups of carp. In normoxia, there was a significant, phylogenetically independent relationship between mass-specific gill surface area and LOEcrit, with the more hypoxia-tolerant carp having smaller gills than their less hypoxia-tolerant relatives. All groups of carp, except the Chinese bream (Megalobrama pellegrini), increased mass-specific gill surface area in response to 48 h of exposure to hypoxia (0.7 kPa) through reductions in the interlamellar cell mass (ILCM) volume. The magnitude of the hypoxia-induced reduction in the ILCM was negatively correlated with LOEcrit (and thus positively correlated with hypoxia tolerance), independent of phylogeny. The hypoxia-induced changes in gill morphology resulted in reduced variation in mass-specific gill surface area among species and eliminated the relationship between LOEcrit and mass-specific gill surface area. While behavioral responses to hypoxia differed among the carp groups, there were no significant relationships between hypoxia tolerance and the Po2 at which aquatic surface respiration (ASR) was initiated or the total number of ASR events observed during progressive hypoxia. Our results are the first to show that the extent of gill remodeling in cyprinids is associated with hypoxia tolerance in a phylogenetically independent fashion. PMID- 24241070 TI - Relationship between fish size and metabolic rate in the oxyconforming inanga Galaxias maculatus reveals size-dependent strategies to withstand hypoxia. AB - The relationship between metabolic rate and body size in animals is unlikely to be a constant but is instead shaped by a variety of intrinsic (i.e., physiological) and extrinsic (i.e., environmental) factors. This study examined the effect of environmental oxygen tension on oxygen consumption as a function of body mass in the galaxiid fish, inanga (Galaxias maculatus). As an oxyconformer, this fish lacks overt intrinsic regulation of oxygen consumption, eliminating this as a factor affecting the scaling relationship at different oxygen tensions. The relationship between oxygen consumption rate and body size was best described by a power function, with an exponent of 0.82, higher than the theoretical values of 0.66 or 0.75. The value of this exponent was significantly altered by environmental P(O2), first increasing as P(O2) decreased and then declining at the lowest P(O2) tested. These data suggest that the scaling exponent is species specific and regulated by extrinsic factors. Furthermore, the external P(O2) at which fish lost equilibrium was related to fish size, an effect explained by the scaling of anaerobic capacity with fish mass. Therefore, although bigger fish were forced to depress aerobic metabolism more rapidly than small fish when exposed to progressive hypoxia, they were better able to enact anaerobic metabolism, potentially extending their survival in hypoxia. PMID- 24241071 TI - Genomic and metabolic preparation of muscle in sockeye salmon Oncorhynchus nerka for spawning migration. AB - Prolonged endurance exercise and fasting are two major metabolic challenges facing Pacific salmon during spawning migrations that often occur over 1,000 km. Because both prolonged exercise and fasting stimulate the oxidation of lipids, particularly in heavily recruited tissues such as muscle, we sought to investigate the regulatory mechanisms that establish and maintain the capacity for substrate oxidation at four separate locations during the final 750 km of nonfeeding migration in sockeye salmon Oncorhynchus nerka. Transcript levels of multiple genes encoding for important regulators of lipid, carbohydrate, and protein oxidation as well as the activity of several important enzymes involved in lipid and carbohydrate oxidation were examined in red and white muscle. We found in both muscle types that the messenger RNA (mRNA) expression of carnitine palmitoyltransferase I isoforms, peroxisome proliferator-activated receptors alpha and beta, and adenosine monophosphate-activated protein kinase beta1 were all significantly higher at the onset compared to later stages of nonfeeding migration. However, the activities of beta-hydroxyacyl-CoA dehydrogenase and citrate synthase were higher only early in migration and only in red muscle. Later in the migration and as muscle lipid stores were greatly depleted, the mRNA levels of hexokinase I and aspartate aminotransferase increased in white muscle. Overall, at the onset of migration, high transcript and metabolic enzyme activity levels in skeletal muscle of sockeye salmon may help support the high rates of lipid oxidation needed for endurance swimming. Furthermore, we suggest that the muscle capacity to use carbohydrates and proteins may be adjusted throughout migration on an as-needed basis to fuel burst exercise through very difficult hydraulic passages in the river and perhaps during mating activities. PMID- 24241072 TI - Postmigratory body condition and ovarian steroid production predict breeding decisions by female gray-headed albatrosses. AB - Carryover effects have been documented in many migratory bird species, but we know little about the physiological mechanisms that mediate those effects. Here we show that the energetic, endocrine, and aerobic characteristics of postmigratory female gray-headed albatrosses (Thalassarche chrysostoma) can affect their decision to breed. All females in this study, whether breeding or not, were secreting ovarian steroids when they arrived at the breeding colony at Bird Island, South Georgia, which suggests that all were responding to seasonal cues. However, deferring, nonbreeding birds were characterized by a steroid profile of high progesterone (P4) and low testosterone (T), whereas breeding birds showed the opposite pattern. Deferring birds also had low body mass, hematocrit, and hemoglobin. These results suggest that postmigratory condition can influence patterns of ovarian steroidogenesis and that the maintenance of high P4 without subsequent conversion to T favors breeding deferral. Whereas breeding females normally convert P4 to T, which is a key deterministic step toward 17beta-estradiol synthesis, vitellogenesis, and follicle development, deferring females did not make this conversion and instead maintained high levels of P4, perhaps due to inhibition of the hydroxylase-lyase enzyme complex, thus rendering them infertile for the current season. Results are discussed within the context of the biennial breeding system of this species, and comparisons with other biennially and annually breeding albatrosses are made. PMID- 24241073 TI - Juvenile nutritional stress affects growth rate, adult organ mass, and innate immune function in zebra finches (Taeniopygia guttata). AB - Developmental conditions may influence many aspects of adult phenotype, including growth and immune function. Whether poor developmental environments impair both growth and immune function or induce a trade-off between the two processes is inconclusive, and the impact of the timing of stress in determining this relationship has so far been overlooked. We tested the hypothesis that the long term effects of nutritional stress on growth, body composition, and immune function in zebra finches (Taeniopygia guttata) are different depending on whether stress is experienced during an early or a juvenile phase (i.e., before or after nutritional independence, respectively). We raised birds on high (H) or low (L) food conditions until posthatch day (PHD) 35 and switched treatments for half of the birds in each of the H and L groups from PHD 36 to 61. We found that unfavorable juvenile conditions (PHD 36-61) increased somatic growth rates and liver mass, body fat, and some aspects of immune function. We also observed a positive relationship between growth and immune function, as individuals that grew faster as juveniles also had better innate immune responses as adults. There was no effect of treatment on basal metabolic rate. These findings demonstrate the importance of juvenile developmental conditions in shaping multiple aspects of the adult phenotype. PMID- 24241074 TI - Seasonal modulation of testosterone during breeding of the rufous-collared sparrow (Zonotrichia capensis australis) in Southern Patagonia. AB - The roles of testosterone (T) during reproduction are often complex and vary among and within vertebrate taxa and locations, making general hypotheses relating T to breeding behavior and success difficult to integrate. In birds, T is thought to influence degrees of territoriality and associated aggression in males to maximize breeding success. Importantly, most work supporting these ideas has been conducted in the Northern Hemisphere. However, accumulating work on tropical species has shown divergent patterns of T in association with breeding behavior. The compilation of work from northern temperate and tropical species suggests that the function of T in relation to breeding behavior varies across latitude and environmental conditions. We investigate the patterns of T in relation to breeding behavior in a subspecies of the rufous-collared sparrow Zonotrichia capensis australis breeding at high latitude in the Southern Hemisphere (55 degrees S). We then compare the T profiles and breeding behaviors of male Z. c. australis to conspecifics breeding in the tropics and congeners in North America to test the hypothesis that environments with breeding seasons of similar lengths will drive similar patterns of T in relation to breeding behavior. We found that Z. c. australis have high levels of T during the early breeding periods when territories are being established and low levels of T during the parental phase of breeding, similar to temperate and Arctic birds in the Northern Hemisphere but unlike tropical Zonotrichia capensis costaricensis. In contrast, we found that Z. c. australis also exhibit similar aggressive behaviors in early breeding and midbreeding, unlike many birds in the Northern Hemisphere. PMID- 24241075 TI - Seasonal variation of resting metabolic rate and body mass in free-living weasels Mustela nivalis. AB - Metabolic rates and body mass of mammals vary seasonally along with ambient temperatures and food availability. At the population level, seasonal changes in metabolic rate and mass can be due to selective mortality or emigration of individuals whose metabolic rate or mass differs from the average for the population. Alternatively, the metabolic rates of individuals can change seasonally, such that the population average increases or decreases due to shifts in the physiology of the overall population. The latter implies that individuals respond in a similar manner to changing seasonal conditions. We studied seasonal changes in body mass (BM) and resting metabolic rate (RMR) in free-ranging male weasels (Mustela nivalis) to test the consistency of these traits in individuals caught in different seasons of the year. At the population level, BM was remarkably stable across the seasons (F(3, 124)=0.25, P=0.9). In contrast, BM- corrected RMR varied significantly between seasons and was the lowest in winter (F(3, 135)=9.13, P<0.0001). We demonstrated that individual weasels were consistent in how their BM and RMR deviated from the seasonal means for the population (intraclass correlation, tau=0.78 and 0.33, respectively). This variation among individuals explained ~76% and 27% of the total variation of BM and basal metabolic rate, respectively. Hence, the relatively constant BM at the population level across seasons is due to a relative constancy of BM in individuals. Our study is one of relatively few research projects that demonstrate that seasonal changes in RMR observed in the wild population are in part due to a consistency in individual responses to changing environmental conditions. PMID- 24241076 TI - Advanced dynamic Doppler flow of the pulmonary artery in a normal population: reference values from 18 to 41 weeks of gestation calculated by automatic Doppler waveform analysis. AB - OBJECTIVE: The aim of the present cross-sectional prospective study was to establish Doppler reference ranges for blood flow velocity waveforms (V max, V mean and V min) and resistance indices (PI, RI) of the fetal pulmonary arteries using the new pulsed-wave color advanced dynamic flow (ADF) Doppler technique. METHOD: Data were collected in 206 low-risk pregnancies at 18-41 weeks of gestation. The measurements were obtained in the proximal pulmonary artery near the first bifurcation in the absence of fetal body or breathing movements. RESULTS: The pulsatility index (PI) in the pulmonary artery showed mean increases of 2.43-3.59 between gestational weeks 18 and 42. A similar pattern was observed for the resistance index (RI) with increases of 0.79-0.90. Increases in systolic (V max), mean (V mean) and end diastolic (V min) blood flow velocities of 36.0 63.3, 10.8-19.9 and 5.71-7.53 cm/s, respectively, were noted during the observation interval. CONCLUSIONS: The ranges for blood flow velocities and impedance indices in the fetal pulmonary artery calculated by the authors may serve as reference values to help distinguish a normal patient population from patients carrying fetuses at high risk for neonatal lung disease in antenatal examinations. PMID- 24241077 TI - Amniotic fluid volume in normal singleton pregnancies: modeling with quantile regression. AB - PURPOSE: To develop uniform and reliable reference ranges for amniotic fluid volume (AFV) across gestation in normal singleton pregnancies using quantile regression (QR). METHODS: An analysis of true AFVs determined by dye-dilution techniques or by direct measurement at cesarean delivery in normal singleton pregnancies. AFV centiles were established by QR, a flexible semi-parametric approach of estimating rates of change across the entire distribution of AFV rather than just in the mean as is observed with standard linear regression. RESULTS: The study evaluated 379 women with normal singleton pregnancies between 16 and 41 weeks gestation. QR was used to determine the association between AFV and gestational age (GA). A second-order quantile regression model indicated a nonlinear relationship between AFV and gestational age at the upper centile range (>=80th percentile). CONCLUSION: This study defines normative centile charts for true AFVs between 16 and 41 weeks gestation in normal singleton pregnancies using QR. This statistical approach more appropriately reflects true AFV across gestation at each centile of interest (e.g. 5th, 50th, 95th, etc.) as compared to standard linear regression. PMID- 24241078 TI - A Longitudinal Approach to Understanding the Relationship Between Symptom Status and QOL. AB - This study demonstrates how a variant of growth curve modeling known as longitudinal parallel-process modeling can yield an understanding of the effect of symptoms on quality of life (QOL). A two-level hierarchical linear model with random intercepts and slopes was implemented within a structural equation modeling approach. The data (N = 367) comes from a large database of persons with HIV-associated illness. Twenty-three symptoms based on the Sign and Symptom Checklist for Persons with HIV disease and items measuring QOL from the general health status scales were used. Each respondent completed from 1 to 11 questionnaires. The number of reported symptoms had a significant association with patient QOL over time. These findings suggest that appropriate symptom management has the potential to improve patient QOL. This study demonstrates how a state-of-the-art longitudinal modeling technique evaluates the relationship between concurrent rates of change in measurements of two relevant variables. PMID- 24241080 TI - Superstrong encapsulated monolayer graphene by the modified anodic bonding. AB - We report a superstrong adhesive of monolayer graphene by modified anodic bonding. In this bonding, graphene plays the role of a superstrong and ultra-thin adhesive between SiO2 and glass substrates. As a result, monolayer graphene presented a strong adhesion energy of 1.4 J m(-2) about 310% that of van der Waals bonding (0.45 J m(-2)) to SiO2 and glass substrates. This flexible solid state graphene adhesive can tremendously decrease the adhesive thickness from about several tens of MUm to 0.34 nm for epoxy or glue at the desired bonding area. As plausible causes of this superstrong adhesion, we suggest conformal contact with the rough surface of substrates and generation of C-O chemical bonding between graphene and the substrate due to the bonding process, and characterized these properties using optical microscopy, atomic force microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. PMID- 24241081 TI - Iron(II)-dependent dioxygenase and N-formylamide deformylase catalyze the reactions from 5-hydroxy-2-pyridone to maleamate. AB - 5-Hydroxy-2-pyridone (2,5-DHP) is a central metabolic intermediate in catabolism of many pyridine derivatives, and has been suggested as a potential carcinogen. 2,5-DHP is frequently transformed to N-formylmaleamic acid (NFM) by a 2,5-DHP dioxygenase. Three hypotheses were formerly discussed for conversion of 2,5-DHP to maleamate. Based on enzymatic reactions of dioxygenase (Hpo) and N-formylamide deformylase (Nfo), we demonstrated that the dioxygenase does not catalyze the hydrolysis of NFM but rather that this activity is brought about by a separate deformylase. We report that the deformylase acts both on NFM and its trans isomer, N-formylfumaramic acid (NFF), but the catalytic efficiency of Nfo for NFM is about 1,400 times greater than that for NFF. In addition, we uncover catalytic and structural characteristics of the new family that the Hpo belongs to, and support a potential 2-His-1-carboxylate motif (HX52HXD) by three-dimensional modeling and site-directed mutagenesis. This study provides a better understanding of 2,5-DHP catabolism. PMID- 24241082 TI - Renoprotective effect of metformin. PMID- 24241083 TI - Urine examination in the era of modern diagnostics. PMID- 24241084 TI - Omega-3 and serum homocysteine level in hemodialysis patients. PMID- 24241085 TI - Bright renoprotective properties of metformin: beyond blood glucose regulatory effects. AB - Metformin, a biguanide drug, is widely prescribed to treat high blood glucose in individuals with type 2 diabetes mellitus. Type 2 diabetes mellitus is a troubling chronic disease and diabetic nephropathy is one of the most important complications of diabetes mellitus. Recent studies suggest that metformin, in addition to its efficacy in treating type 2 diabetes, may also have therapeutic efficacy in other conditions, including diabetic nephropathy or ameliorative property against tubular cell injury. Moreover, metformin significantly decreases albuminuria in patients with type 2 diabetes mellitus. However, the exact mechanisms beyond the effect of metformin on blood glucose are still unknown. Recent studies suggest that the therapeutic effect of metformin is mediated by its action on adenosine monophosphate-activated protein kinase in tissues. Various investigations show that metformin decreases intracellular reactive oxygen species. Metformin protects against tubular injury by restoring the biochemical alterations and regulation of oxidative stress on renal tubules. It also protects podocytes in nephropathy of diabetes. These findings can more strongly potentiate the clinical use of metformin in the prevention of nephropathy of diabetes. In this regard, to better understand the metformin nephroprotective properties, more experimental rat models and clinical studies are needed. PMID- 24241086 TI - Pediatric kidney transplantation: kids are different. AB - The pediatric kidney transplant recipient differs from the adult recipient in many ways, including immune responsiveness, drug metabolism and clearance, perfusion of transplanted organs, and risk for posttransplant lymphoproliferative disease. Pediatric patients also have special quality of life issues such as cosmetic side effects of medications, stunted growth and sexual maturation, and separation from their peers. Congenital urological anomalies and glomerulosclerosis are the most common causes of pediatric end-stage renal disease. In the pediatric patients, consideration for preemptive transplantation should be first and arteriovenous fistula placement second. Pediatric patients should receive priority for kidneys from deceased donors to shorten the wait time for transplant. Fevers or changes in blood pressure may identify allograft dysfunction weeks before changes in creatinine occur. Thus, monitoring serum creatinine level is a poor indicator of allograft dysfunction in this setting. There is great concern about nonadherence to immunosuppressive therapy as children reach the stage of adolescence. This report highlights these and other important differences in the evaluation and management of the pediatric kidney transplant recipients compared with the adult and provides practical guidance to the practitioners involved in caring for such patients. PMID- 24241087 TI - A workshop on urinalysis and a survey on urine microscopy among kidney centers of Iran. AB - Urinalysis is a mandatory diagnostic tool for the evaluation of patients with kidney diseases. A workshop on urinalysis was held for nephrologists in Isfahan, Iran, on October 11-12, 2012. After the presentation of the results of a survey of the nephrology centers of Iran on urine microscopy, the most important aspects of urinalysis were presented and discussed. These included the following: (1) urinalysis by dipstick, which provides results in a few seconds, is simple to use, has a low cost, and is used worldwide for screening purposes, in spite of some limitations; (2) measurement of proteinuria by 24-hour urine collection, which still represents the reference method in spite of limitations due to frequent over or under collection errors; (3) protein-creatinine ratio in a random urine sample, which is recommended by international guidelines as an alternative to the measurement of 24-hour protein excretion; (4) microalbuminuria, which is seen as a marker of systemic endothelial damage; and (5) the urinary sediment, which is underused even among nephrologists in spite of the relevant diagnostic information it can supply in a wide spectrum of kidney diseases. PMID- 24241088 TI - Renal papillary adenoma in autosomal dominant polycystic kidney disease. PMID- 24241089 TI - Lowering effect of valsartan on fetuin-A in type 1 diabetes mellitus. AB - INTRODUCTION: Fetuin-A (A2-HS-glycoprotein) is a protein that plays several functions in human physiology and pathophysiology. The role of fetuin-A in type 1 diabetes mellitus (DM) has been less studied. We investigated the serum levels of fetuin-A in type 1 diabetic patients with microalbuminuria. Furthermore, the blocking effect of renin-angiotensin-aldosteron system on serum levels of fetuin A was assessed. MATERIALS AND METHODS: From January 2010 to May 2011, 32 patients with type 1 DM with confirmed microalbuminuria were included in this study in Isfahan, Iran. Serum fetuin-A levels before and 8 weeks after valsartan administration were measured. In addition, serum lipid profile, creatinine, hemoglobin A1c, and urine microalbuminuria were determined. RESULTS: The mean age of participants was 21.65 +/- 0.38 years. Before valsartan administration, the mean values of fetuin-A were not significantly different between males and females (64.22 +/- 1.77 ng/mL versus 61.39 +/- 3.35 ng/mL, respectively). After valsartan administration, serum levels of fetuin-A and urine albumin-creatinine significantly decreased. A negative correlation was observed between serum fetuin A level after valsartan administration and serum low-density lipoprotein cholesterol level (P = .007, r = -0.507). CONCLUSIONS: Administration angiotensin receptor blockers concomitantly decreases fetuin-A levels and urine albumin levels. PMID- 24241090 TI - Association between visfatin levels and coronary artery disease in patients with chronic kidney disease. AB - INTRODUCTION: Visfatin (also known as pre-B cell colony-enhancing factor) is increased in patients with chronic kidney disease and has been linked with coronary atherosclerosis. Given that it has been reported that visfatin plays a role in endothelial dysfunction in chronic kidney disease patients, we examined associations between visfatin levels and several markers related to atherosclerosis. MATERIALS AND METHODS: The association between visfatin and atherosclerotic risk factors was studied in 173 chronic kidney disease patients (130 men and 43 women). Serum levels of visfatin were measured by the enzyme linked immunosorbent assay. RESULTS: With increasing visfatin tertiles, patients proved to have a larger number of vessels with stenosis and a higher likelihood of coronary artery disease, as well as having incrementally lower estimated glomerular filtration rate and serum albumin and higher total leukocyte, neutrophil, and monocyte counts; high-sensitivity C-reactive protein; and brain natriuretic peptide levels. Visfatin showed significant positive correlations with low-density lipoprotein cholesterol, uric acid, blood urea nitrogen, creatinine, brain natriuretic peptide, E-selectin, total leukocyte count, neutrophil count, and high-sensitivity C-reactive protein, and a significant negative correlation with estimated glomerular filtration rate and albumin. Only E-selectin was independently associated with visfatin in multiple linear regression analysis. CONCLUSIONS: This study indicates that plasma visfatin levels are significantly higher in the presence of coronary artery disease and are correlated with E-selectin levels, which suggest that increased plasma visfatin may be involved in the pathogenesis of coronary atherosclerosis in CKD patients. PMID- 24241091 TI - Comparison of fetuin-A, vitamin D, monounsaturated fatty acid, and vascular calcification on plain radiography between dialysis modalities. AB - INTRODUCTION: Low fetuin-A and vitamin D and high monounsaturated fatty acid (MUFA) contents are associated with vascular calcification (VC) in dialysis patients. We aimed to demonstrate the difference in fetuin-A, vitamin D, MUFA, and VC on plain radiography between patients on hemodialysis and peritoneal dialysis (PD). MATERIALS AND METHODS: We recruited 31 hemodialysis and 30 PD patients. We examined plain radiography of the feet, hands, pelvis, and lateral lumbar spine and defined significant VC as abdominal aortic calcifications scores of 5 and higher, VC scores of the hands and pelvis of 3 and higher, or arterial media calcifications of the feet on plain radiography. RESULTS: The mean age, dialysis duration, and prevalence of VC on plain radiography were not significantly different in PD patients compared to hemodialysis patients. However, fetuin-A and MUFA were significantly higher, whereas serum albumin and 25-hydroxyvitamin D were significantly lower in PD patients compared to hemodialysis patients. Hemodialysis patients who demonstrated significant VC on plain radiography had longer dialysis vintage, higher prevalence of coronary artery disease, and higher MUFA than patients without significant VC. Peritoneal dialysis patients who demonstrated significant VC on plain radiography had lower fetuin-A levels and higher C-reactive protein than patients without significant VC. Fetuin-A was an independent risk factor related with VC on plain radiography in PD patients. CONCLUSIONS: Fetuin-A, 25-hydroxyvitamin D, and MUFA were significantly different, although the prevalence of VC on plain radiography was not different according to dialysis modality. PMID- 24241092 TI - Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. AB - INTRODUCTION: Increased oxidative stress, inflammation, and malnutrition are present in hemodialysis patients and these factors exacerbate cardiovascular comorbidities. Vitamin E and alpha-lipoic acid (ALA) may have a protective role against cardiovascular disease risk factors via anti-oxidative and anti inflammatory properties. The aim of this study was to evaluate the effect of ALA and vitamin E administration (alone or combined) on hemodialysis-induced stress oxidation, inflammation, and malnutrition. MATERIALS AND METHODS: In a randomized placebo-controlled trial, we examined the effects of 2-month supplementation by vitamin E and ALA (alone or combined) on biomarkers of lipid peroxidation (malondialdehyde), inflammation (high-sensitivity C-Reactive protein and interleukin-6), and malnutrition (Subjective Global Assessment and body mass index) in 85 hemodialysis patients receiving ALA (600 mg), vitamin E (400 IU), ALA and vitamin E, and placebo. RESULTS: After supplementation, no significant changes were observed in malondialdehyde level; however, there was a decrease in the ALA and vitamin E group during the period of the study. Also, a nonsignificant decrease was seen in the high-sensitivity C-Reactive protein concentration of the interventional groups. Supplementation of vitamin E with and without ALA significantly reduced interleukin-6 concentration. A significant improvement was observed in malnutrition status of all groups. CONCLUSIONS: Vitamin E and ALA supplementation, especially their combination, might improve inflammation and malnutrition status, which suggest it as a potential preventive strategy against CVD among end-stage renal disease patients. PMID- 24241093 TI - Hemodialysis in children: eleven years in a single center in Egypt. AB - INTRODUCTION: The objective of this study was to report the clinical characteristics and outcomes of children with end-stage renal disease under regular hemodialysis in a dialysis unit in Egypt. MATERIALS AND METHODS: Ninety children with end-stage renal disease were included in this study and their charts over the past 11 years (from January 2001 to January 2012) were reviewed. RESULTS: The mean age of the patients at the start of hemodialysis was 5.6 +/- 1.4 years. The main causes of end-stage renal disease were glomerular diseases (35.6%), unknown etiology (33.3%), and urological problems (17.8%). Hospital admissions were due to hypertensive attacks, cardiac problems, arteriovenous shunt complications, and infections. Only 3 children received a kidney transplant and 24 (26.7%) died during the 11-year follow-up. Eight patients died of heart failure, 5 due to sepsis, and 4 due to unexplained causes. CONCLUSIONS: Maintaining an appropriate care for children with end-stage renal disease is quite difficult in developing countries due to factors such as late referral, poor medical service utilization, limitation of financial resources, and limitations to transplantation. As a result, maintaining on hemodialysis for long periods imposes a high risk of complications. PMID- 24241094 TI - Seroprevalence of antibodies against varicella-zoster virus among prevalent hemodialysis patients. AB - INTRODUCTION: Varicella-zoster virus (VZV) can cause life-threatening disease in immunosuppressed patients, including kidney allograft recipients. This study was designed to evaluate the immune status of the cohort of hemodialysis patients, who could potentially be candidates for kidney transplantation, against VZV, and to determine the correlation between the self-reported history of chickenpox infection and the VZV antibody status in this population. MATERIALS AND METHODS: Serologic testing for VZV was performed for 187 patients at different age groups receiving hemodialysis treatment at Hasheminejad Hospital, Tehran. The enzyme immunoassay method was used for determining immunoglobulin G antibodies against VZV. RESULTS: A total of 187 patients, aged 18 to 88 years (mean, 57.5 +/- 16.2 years), were examined. Ninety-five patients (50.8%) were men. Overall, 183 patients (97.9%) were found to be seropositive for VZV. No significant correlation was observed between patients' history of chickenpox disease and seropositivity of VZV. The sensitivity, specificity, and positive and negative predictive values of patients' self-reported history was 39.3%, 50%, 97.2%, and 1.7%, respectively. CONCLUSIONS: Serologic screening for VZV in patients who are candidates for transplantation is essential to determine their immune status prior to transplant surgery. We suggest that this population be considered as the target group for future immunization programs in Iran. PMID- 24241095 TI - Effect of omega-3 supplementation on serum level of homocysteine in hemodialysis patients. AB - INTRODUCTION: Patients with end-stage renal disease are at a high risk of adverse cardiovascular events. Elevated level of homocysteine is an important risk factor for cardiovascular morbidity and mortality in dialysis patients. There are some strategies for reduction of serum homocysteine level in these patients, including folate and vitamin supplementation. The aim of the present study was to evaluate the effect of omega-3 supplementation on serum homocysteine level in patients on hemodialysis. MATERIALS AND METHODS: In a randomized controlled trial, 100 hemodialysis patients were assigned into two groups to receive omega-3 (oral capsule, 3 g/d) or placebo for 2 months. Complete blood count, blood urea nitrogen, serum creatinine, serum lipids, and serum homocysteine levels were measured before the study and after 2 months at the end of study. RESULTS: Of 100 patients, 6 in each group were excluded, and 44 patients in each group completed the study. There were no significant differences regarding the age, sex, and the number of dialysis sessions per week between the two groups. No difference was observed between the two groups in the laboratory investigations at the end of the study, except for a significant reduction in serum homocysteine level in the omega-3 group as compared to the placebo group (P = .03). CONCLUSIONS: Our study showed a significant reduction regulated by omega-3 supplementation in serum homocysteine level which is a cardiovascular risk factor among hemodialysis patients. Omega-3 can be considered as another homocysteine-reducing agent in this population. PMID- 24241096 TI - Oxidative stress in Egyptian hemodialysis children. AB - INTRODUCTION: Nitric oxide (NO) is one of the endothelium-dependent relaxing factors released by the vascular endothelium. It is decreased in chronic kidney disease. It was found that higher levels of circulating proinflammatory cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL 6, and IL-13 are associated with mortality. The aim of our study was to evaluate the disturbance in NO in chronic kideny failure and its relationship with hypertension and inflammatory and nutritional parameters, as indirect indexes of uremic oxidative stress. MATERIALS AND METHODS: This study included 31 children consisting of 23 children, aged from 4 to 18 years old, with ESRD, on regular hemodialysis, and 8 children admitted to hospital for other diseases (control group). Predialysis blood samples were tested for IL-1beta, TNF-alpha, and NO, and were compared with the control group. RESULTS: Serum levels of TNF-alpha and IL-1beta were significantly higher in children on hemodialysis as compared to the control group (TNF-alpha, 104.54 +/- 17.31 pg/mL versus 48.19 +/- 6.28 pg/mL, P = .005; IL-1beta, 5.35 +/- 0.75 pg/mL versus 2.13 +/- 0.61 pg/mL, P = .02; respectively). However, the levels of NO, albeit higher in this group had no significant difference with the controls. CONCLUSIONS: The levels of cytokines are high in pediatric patients on hemodialysis, which reflects a state of oxidative stress. PMID- 24241097 TI - Use of herbal remedies among patients undergoing hemodialysis. AB - This study aims to determine the prevalence, types, and associated factors for the use of herbal remedies in hemodialysis patients. Two hundred participants were selected by stratified sampling and were systematically interviewed. One hundred and twenty-six patients (63%) had used herbal remedies some time since their initiation of dialysis treatment. The users of herbal remedies had a significantly older age than nonusers, but no other significant differences were observed. The most prevalent complaints that led to herbal remedies use were gastroenterological complaints, flushing, and excessive thirst. Cichorium intybus, Borage officinalis, Mentha longifolia, and Matricaria recutita were the most prevalently used herbs in our patients. More study should be done on safety and efficacy of these herbs for hemodialysis patients. PMID- 24241098 TI - Skin grafting for necrotizing fasciitis in a child with nephrotic syndrome. AB - Necrotizing fasciitis is a rare complication of nephrotic syndrome in children, with a high mortality rate. We report a case with successful outcome with judicious intravenous antibiotics and skin grafting of the bilateral lower thighs. PMID- 24241099 TI - Kartagener syndrome with focal segmental glomerulosclerosis. AB - Primary ciliary dyskinesia is characterized by congenital impairment of mucociliary clearance. Kartagener syndrome (KS) is a clinical variant of primary ciliary dyskinesia which is involved in situs inversus associated with chronic respiratory infections. In addition, glomerular disease in KS syndrome is rare and reported cases are limited. We had a 27-year-old female patient with KS who presented with proteinuria, hematuria, normal kidney function, and a family history of systemic lupus erythematosus. Kidney biopsy showed segmental scar with adhesion to Bowman capsule, which was indicative of focal segmental glomerulosclerosis. PMID- 24241100 TI - Rituximab in steroid-dependent nephrotic syndrome. AB - Treatment of steroid-dependent nephrotic syndrome, particularly in patients who have failed to respond to multiple immunosuppressive drugs, remains challenging. Rituximab represents a new off-label therapeutic option. Here, we report the use of rituximab in 7 children with steroid-dependent nephrotic syndrome with various histological backgrounds who failed to maintain remission with other immunosuppression regimens. All patients received rituximab infusion, 750 mg/m(2) in 2 doses, 2 weeks apart, and the subsequent doses were adjusted by clinical response. In all patients, complete B-cell depletion was observed after the first course of rituximab. Follow-up for at least 12 months showed sustained remission in 6 children. We conclude that rituximab can reduce the risk of relapses, reduce the burden of immunosuppression, and at least, offer a better control of steroid dependent nephrotic syndrome with minimal doses of immunosuppressive agents and steroids. PMID- 24241101 TI - Re: Atypical clinical course of antineutrophil cytoplasmic autoantibodies associated vasculitis. PMID- 24241102 TI - Genetic analysis of waxy locus in rice (Oryza sativa L.). AB - Inheritance of waxy locus was studied in crosses of a waxy variety with four non waxy parents having high-, intermediate-, low- or very low-amylose content. The analysis for amylose content was done on a single grain basis in parents, F1, F2, B1F1, and B2F1 seeds. The waxy parent lacking synthesis of amylose content was found to differ from the ones having high-, intermediate-, low- or very low amylose content by one gene with major effect. Dosage effects for amylose content were observed to have great influence on segregation pattern and efficiency of selection. Selection efficiency for amylose content can be enhanced by selecting for endosperm appearance in early segregating generations. PMID- 24241103 TI - Starch characteristics in cultures of normal and mutant maize endosperm. AB - Vigorously growing suspension cultures of 'normal', amylose-extender (ae) and waxy (wx) maize endosperm were established from near isogenic lines of maize inbred A636. The recovery of the ability to produce vigorous cultures of ae and wx endosperm by backcrossing demonstrate the genetic control of endosperm growth in vitro. Phenotypic expression of the endosperm mutants in culture was studied by examining the properties of starch accumulated in endosperm cultures and starch from developing and mature kernels of the same genotype. After 9 months in culture, the amylose contents of the starch in normal callus tissue and normal endosperm tissue were not significantly different, 28.2% and 31.7%, respectively. Starch granules from normal cultures and endosperm stained blue-black with iodine and were round to polygonal in shape. The starches of wx endosperm and callus cultures contained no amylose, and wx starch granules stained brown-orange with iodine. Although, wx starch granules were primarily round, a few granules with "jagged edges" were observed in starch samples isolated from cultures and kernels. The percent amylose in starch from ae callus was significantly lower than the amylose content of starch from ae endosperm tissue, 39.9% and 67.7%, respectively. Starch granules from ae endosperm and cultures were smaller than normal and wx starch granules. Irregular starch granules which are typical of ae endosperm were present in ae callus tissue, but were less frequently observed. We conclude that specific endosperm mutant phenotypes are expressed in vitro. PMID- 24241104 TI - Repressing the expression of self-incompatibility in crucifers by short-term high temperature treatment. AB - The effect of short-term high temperature on the expression of self incompatibility was studied in detached flowers of Brassica oleracea, B. campestris and Raphanus sativus. The expression of self-incompatibility was repressed by treatment of pistils at 40 degrees C for 15 minutes. Treatment at 50 degrees C repressed self-incompatibility but it also disturbed pollen tube elongation into stylar tissue. S-glycoproteins did not show any quantitative changes during the intact pistil treatment under 50 degrees C. Callose was occasionally found in the treated papilla where the self pollen tube penetrated. The repressing effect of the 40 degrees C treatment was found to be reversible, and this reversibility depended upon the environmental temperature of plant. Plants grown at 15/5 degrees C (day/night temperature) completely recovered self incompatibility 2 h after treatment, while those grown at 20/10 degrees , 25/15 degrees C did not. The reversibility of the expression of self-incompatibility correlated with the distortion of plasma membrane in the papilla. It is considered that high temperature affects the pollen tube penetration system in pistils rather than the recognition system between pistils and pollen. The treatment of dehiscing anthers at 40 degrees C killed the pollen. PMID- 24241105 TI - Nucleic acids in mummified plant seeds: screening of twelve specimens by gel electrophoresis, molecular hybridization and DNA cloning. AB - Twelve seed specimens of varying ages and from different archaeological sites were analyzed for the presence of polymerized DNA and RNA. Amongst the samples tested, one of Vitis vinifera from an archaeological site in Iran (2,000-3,000 B.C.) was found to be completely devoid of nucleic acids. Zea mais seeds of Precolumbial age from Peru (about 800 A.D.) contained depolymerized DNA and RNA. Samples of Vitis vinifera and Rubus sp. from a Lombard archaeological site (800 A.D.) as well as radiocarbon dated seeds from the site of the "Spring Sanctuary" near Metaponto (I-IV century B.C.) were found to contain polymerized DNA and rRNA bands. However the electrophoretic properties of the rRNAs in one case and hybridization experiments performed with cloned seed DNA in the other, clearly demonstrated that the polymerized nucleic acids were not of plant origin. PMID- 24241106 TI - Inbreeding under a cyclical mating system. AB - General recursion formulae for the coefficient of inbreeding under a cyclical mating system were derived in which one male and one female are selected from each of the n families per generation (population size N = 2 n). Each male is given the family number of his sire in each generation, while his mate comes from another family, varying systematically in different generations. Males of the r th family in generations 1, 2, 3,..., t' = n-1 within each cycle mate with females from families r+1, r+2, r+3,..., r+t' to produce generations 2, 3, 4,..., t'+1=1, respectively. The change in heterozygosity shows a cyclical pattern of rises and falls, repeating in cycles of n-1 generations. The rate of inbreeding oscillates between <-3% to >6% in different generations within each cycle, irrespective of the population size. The average rate of inbreeding per generation is approximately 1/[4 N-(Log2N+1)], which is the rate for the maximum avoidance of inbreeding. The average inbreeding effective population size is approximately 2 N-2. PMID- 24241107 TI - Chromosome pairing in a Lolium temulentum X Lolium perenne diploid hybrid with a low chiasma frequency. AB - Despite an average difference of about 50% in DNA amount, homoeologous chromosomes pair effectively at first metaphase in the diploid interspecific hybrid between Lolium temulentum and Lolium perenne. However, in the presence of accessory B chromosomes and "diploidising genes" pairing at metaphase I is severely reduced. Reconstruction of serial electron micrographs through pollen mother cell nuclei show that synaptonemal complexes are formed at pachytene between not only homoeologous but also non-homologous chromosome segments resulting in multivalent formation. These associations are largely ineffective in terms of chiasma formation and degenerate at late pachytene. It is highly probable that the pairing determinants exercise their control on chromosome pairing largely by prohibiting the siting of crossovers in homoeologously paired chromosome segments. PMID- 24241108 TI - Hairy root transformation in alfalfa (Medicago sativa L.). AB - The widely cultivated forage legume alfalfa (Medicago sativa L.) was transformed with the agropine type Agrobacterium rhizogenes NCPPB 1855. Sterile root and callus cultures were derived from tumorous hairy roots which were easily obtained independent of the plant variety or genotype. Plant regeneration, via somatic embryogenesis, was achieved only when a selected alfalfa line, characterized by high regenerative capability, was utilized. Genetic transformation was confirmed by the presence of agropine and T-DNA. Phenotypic alterations, mainly affecting the root system, were observed in transformed plants. The possibility that T-DNA induced variations could be useful in the improvement of M. sativa is discussed. PMID- 24241109 TI - Morocco as a possible domestication center for barley: biochemical and agromorphological evidence. AB - The distribution of genetic variants of a group of low molecular weight, chloroform-methanol soluble proteins (CM proteins), among Moroccan and non Moroccan accessions of Hordeum spontaneum and among selections from several Moroccan landraces of H. vulgare and cultivars of the same species with widespread European origin, suggests that domestication of barley might have taken place in Morocco. An agromorphological characterization of the H. spontaneum accessions further supports this hypothesis. The possible Moroccan origin of the French cultivar 'Hatif de Grignon' and of several Spanish 6-rowed barleys is also presented. PMID- 24241110 TI - Theoretical value of estimates of general combining ability in the autotetraploid crop. AB - The means of half-sib progenies have been indicated as selection criteria for intra-population improvement while the average of the means of full-sib progenies in diallel analyses have been proposed as predictors, in part, of the means of untested synthetic varieties. When these measures based on progeny means are expressed as deviations from a defined greater population of crosses, they are often termed the general combining ability (GCA). In this study the GCA estimates or a facsimile were theoretically investigated for the one locus, digene, autotetraploid model to verify the genetic basis and its value for selection and prediction in the presence of a naturally occurring phenomena of autopolyploids called gametic disequilibrium with three types of non-additive inheritance. Two breeding objectives were envisioned, the selection of best parents with recurrent selection based on GCA in the continued development of elite populations and the prediction of advanced generation synthetic variety performance. The first generation means of progenies with a potential bias due to gametic disequilibrium were compared to GCA estimation of same progenies in the absence of gametic disequilibrium. The results indicated that testcrossing plants to a population without gametic disequilibrium could be used for selection of best parents. The gametic disequilibrium in the cross may increase or depress selection response dependent on the array of genotypes which happen to be evaluated, on the type of genic action at the locus, and on the frequency of the desirable allele in the testor population. The GCA estimates for prediction of synthetic performance were potentially biased by gametic disequilibrium. An assumption of pollination by the same array of gametes was made for all plants, but obviously was unrealistic for GCA estimation with partial diallels, or with no selfing, and in other situations. The GCA estimate was shown to be an unreliable predictor of synthetic variety performance. When it was assumed that different plants were pollinated by different arrays of gametes, a more realistic situation, no genetic interpretation of GCA values was possible even with purely additive gene action at the locus. PMID- 24241111 TI - Cytogenetic studies in the genus Zea : 1. Evidence for five as the basic chromosome number. AB - New cytological evidence supporting x = 5 as the basic chromosome number of the genus Zea has been obtained as a consequence of our analysis of the meiotic configurations of Zea mays ssp. mays, Z. diploperennis, Z. perennis and of four F1 artificial interspecific hybrids. Z. mays ssp. mays (2n = 20) presents regular meiosis with 10 bivalents (II) and is considered here as a typical allotetraploid (A2A2B2B2). In Z. diploperennis (2n = 20) 10II are formed in the majority of the cells, but the formation of 1III + 8II + 1I or 1III + 711 + 3I in 4% of the cells would indicate its segmental allotetraploid nature (A1A1B1B1). Z. perennis (2n = 40) had 5IV + 10II in 55% of the cells and would be considered as an auto allooctoploid (A'1A'1A''1A''1C1C1C2C2). Z. diploperennis x Z. mays ssp. mays (2n = 20) presents 10II in ca. 70% of the cells and no multivalents are formed. In the two 2n = 30 hybrids (Z. mays ssp. mays x Z. perennis and Z. diploperennis x Z. perennis) the most frequent meiotic configuration was 5III + 5II + 5I and in 2n = 40 hybrid (Z. diploperennis x Z. perennis) was 5IV + 10II. Moreover, secondary association was observed in the three abovementioned tetraploid taxa (2n = 20) where one to five groups of two bivalents each at diakinesis-metaphase I was formed showing the affinities between homoeologous genomes. The results, as a whole, can be interpreed by assuming a basic x = 5 in this polyploid complex. The main previous contributions that support this working hypothesis are reviewed and its phylogenetic implications studied are discussed. PMID- 24241112 TI - Sid: a Mendelian locus controlling thylakoid membrane disassembly in senescing leaves of Festuca pratensis. AB - A spontaneous mutation arising in Festuca pratensis has the effect of stabilizing the pigmentproteolipid complexes of thylakoid membranes so that leaf tissue does not turn yellow during senescence. Inheritance of the non-yellowing character was analysed in crosses between the wild-type cultivar Rossa and a mutant line Bf 993. Electrophoretic variants of cytoplasmic phosphoglucoisomerase coded by alleles of the nuclear gene Pgi-2 were used to identify hybrids during intercrossing. About 96% of the F1 progeny were heterozygous and all were phenotypically yellowing. In the F2 generation yellow ? green segregated in a ratio of 2.14?1, not significantly different from 3?1. In the backcross between F1 and Bf 993 the ratio was 1?1 yellow ? green. There was no indication of linkage to Pgi-2. Senescence of detached Bf 993 and Rossa leaves was compared with that of the F1 hybrid. The hybrid behaved in an essentially identical fashion to the wildtype parent, and in marked contrast to the mutant, in all aspects of the senescence syndrome investigated, including loss of chlorophyll, carotenoids and the light-harvesting chlorophyll-protein of thylakoid membranes, and elevation of the particulate protein ? chlorophyll ratio in the terminal stages. It is concluded that there exists in Festuca pratensis a nuclear gene, designated Sid (senescence-induced degradation) which regulates turnover of hydrophobic components of photosynthetic membranes in ageing leaf tissue and which occurs in at least two allelic forms, y (yellow) dominant over g (green). PMID- 24241113 TI - Trait-based analyses for the detection of linkage between marker loci and quantitative trait loci in crosses between inbred lines. AB - Methods are presented for determining linkage between a marker locus and a nearby locus affecting a quantitative trait (quantitative trait locus=QTL), based on changes in the marker allele frequencies in selection lines derived from the F-2 of a cross between inbred lines, or in the "high" and "low" phenotypic classes of an F-2 or BC population. The power of such trait-based (TB) analyses was evaluated and compared with that of methods for determining linkage based on the mean quantitative trait value of marker genotypes in F-2 or BC populations [marker-based (MB) analyses]. TB analyses can be utilized for marker-QTL linkage determination in situations where the MB analysis is not applicable, including analysis of polygenic resistance traits where only a part of the population survives exposure to the Stressor and analysis of marker-allele frequency changes in selection lines. TB analyses may be a useful alternative to MB analyses when interest is centered on a single quantitative trait only and costs of scoring for markers are high compared with costs of raising and obtaining quantitative trait information on F-2 or BC individuals. In this case, a TB analysis will enable equivalent power to be obtained with fewer individuals scored for the marker, but more individuals scored for the quantitative trait. MB analyses remain the method of choice when more than one quantitative trait is to be analyzed in a given population. PMID- 24241114 TI - Mitochondrial DNA diversity in the genera of Triticum and Aegilops revealed by southern blot hybridization. AB - Southern blot hybridization of total DNA to defined mitochondrial DNA sequences provides a sensitive assay for mtDNA variation in the genera of Triticum and Aegilops. A clear distinction between cytoplasms of tetraploid species sharing the "AG" haploid genome is reported for the first time. The Sitopsis section of the genus Aegilops showed the most extensive intra- and inter-specific variation, whereas no variation could be detected among the cytoplasms of polyploid Triticum species (wheats) sharing the AB haploid genome. Extensive cytoplasmic intraspecific diversity was revealed in Ae. speltoides. PMID- 24241115 TI - Generation mean analyses for flowering and maturity in Indian mustard (Brassica junces (L.) Czern & Coss). AB - Components of generation means were partitioned for days to flower initiation and maturity in three crosses of Indian mustard (Brassica juncea (L.) Czern and Coss) cultivars. A linked digenics model was adequate for flowering in cross II and maturity in Cross I. All three types of digenic interactions among the linked pairs of genes, additive X additive (i), additive X dominance (j) and dominance X dominance (1), contributed significantly in the inheritance of flowering in cross II and maturity in cross I. A complete association among the genes of greater effects in higher mean parent was detected for flowering in cross II and maturity in Cross I. Duplicate epistasis was evident for flowering in Crosses I and II and maturity in Crosses I and III.Inadequacy of all the fitted models for days to flowering in Cross III and maturity in Cross II indicated the presence of higher order interactions. PMID- 24241116 TI - Molecular divergence of alfalfa somaclones. AB - Plantlets were regenerated from alfalfa callus following passage through a tissue culture medium which contained gibberellic acid. A proportion of these plantlets showed obvious morphological variations. Leaflet, stem and petiole tissue of these plants were extracted to yield a soluble protein homogenate which was characterized by polyacrylamide gel electrophoresis. Over 18 individual protein bands were resolved and visualized by staining with coomassie blue G250. Electrophoretic gels from regenerated plantlets and from the parent plant were scanned spectrophotometrically and analyzed. The relative quantity of each of the proteins resolved from plants was correlated with proteins of other plants via the Pearson's product-moment correlation. Cluster analysis was then performed using these correlation coefficients to judge relatedness among somaclones and the parent plant. Two of 22 somaclones (9.1%) differed significantly from the parent and from the other somaclones judged by quantitative protein pattern variations. Three distinctive lineages through tissue culture produced plantlets. Using a discriminant analysis strategy somaclones could be grouped according to lineage with 80.8% accuracy based upon distinctions between protein electrophoretic patterns. Two of the somaclone lineage groupings showed no overlap with the parental grouping which indicated significant molecular divergence of these plantlets as judged by quantitative protein differences. PMID- 24241117 TI - Location of genes coding isozyme markers on Aegilops umbellulata chromosomes adds data on homoeology among Triticeae chromosomes. AB - Zymogram analysis was used to identify the Aegilops umbellulata chromosomes that carry the structural genes for particular isozymes. Wheat, Aegilops and wheat Aegilops hybrid derivative lines (which contained identified Aegilops chromosomes) were tested by gel electrophoresis for isozymes of particular enzymes. It was found that Aegilops chromosome A (nomenclature according to G. Kimber 1967) carries a structural gene for 6-phosphogluconate dehydrogenase, Aegilops chromosome B carries structural genes for glucose phosphate isomerase and phosphoglucose mutase, Aegilops chromosome D carries genes for leaf peroxidases, Aegilops chromosome E carries structural genes for endosperm peroxidases, acid phosphatases and leaf esterases, Aegilops chromosome F carries a gene for embryo plus scutellum peroxidases and Aegilops chromosome G carries structural genes for endosperm alkaline phosphatases, leaf alkaline phosphatases and leaf esterases. The results obtained indicate that chromosome B is partially homoeologous of the wheat chromosomes of group 1 and 4, and chromosome E is partially homoeologous of wheat chromosomes of groups 7 and 4. Circumstantial evidence is also provided about the possible association between chromosomes C, D and A of A. umbellulata respectively with chromosomes 5, 2 and 1 of wheat. PMID- 24241118 TI - The induction of hexaploidy in cherry rootstocks using in vitro regeneration techniques. AB - An in vitro regeneration technique using root callus has been combined with colchicine application to produce hexaploid plants from the sterile triploid cherry rootstock Colt. Colchicine (50 mg/l) was applied together with auxin (IBA) (3 mg/l) either before or after root primordium formation in single excised micropropagating shoots. In both cases shoots were regenerated in vitro from the putative hexaploid roots. Both methods produced hexaploid plants but more than 70% of the regenerated clones were still triploid. The hexaploid plants were distinguishable from the triploids on morphological as well as cytogenetic grounds. Quantitative characters such as leaf length/breadth ratio, stomatal length and density in the hexaploids were significantly different from both regenerated and non-regenerated triploids. PMID- 24241119 TI - The nature of 2-locus epistatic interactions in animals: evidence from Sewall Wright's guinea pig data. AB - The nature of epistatic interactions affects covariance between relatives and the expression of heterosis in various crossbred genotypes. The investigation of these interactions for metric traits requires large data sets of a suitable type. Data from Sewall Wright's early work with guinea pigs are used to compare the goodness-of-fit of seven biological models of 2-locus interaction for the six out of eleven traits in which epistatic effects are apparent. The model equivalent to additive x additive epistasis gives the best general fit over traits, with an average transformed R(2) value significantly greater than that of the next best fitting model (P<0.05). This result is compatible with results from the one other study in this area, using data from mice. It is concluded that, based on results available to date, the additive x additive 2-locus model of epistatic interaction appears most suitable for reduced genetic models. PMID- 24241120 TI - Genetic transfer of resistance to powdery mildew and of an associated biochemical marker from Aegilops ventricosa to hexaploid wheat. AB - Resistance to powdery mildew, caused by the fungus Erysiphe graminis f.sp. tritici, has been transferred from Aegilops ventricosa (genomes D(v)M(v)) to hexaploid wheat (Triticum aestivum, ABD). In two transfer lines, H-93-8 and H-93 35, the resistance gene was linked to a gene encoding protein U-1, whereas one line, H-93-33, was resistant but lacked the molecular marker, and another line, H 93-1, was susceptible but carried the gene for U-1, indicating that the original M(v) chromosome from Ae. ventricosa, carrying the two genes, had undergone recombination with a wheat chromosome in the last two lines. PMID- 24241121 TI - Inheritance of partial resistance to powdery mildew in spring wheat. AB - Four spring wheat (Triticum aestivum L.) cultivars exhibiting partial resistance to powdery mildew induced by Erysiphe graminis f.sp. tritici were crossed to a common susceptible cultivar to study the inheritance of resistance. The genetic parameters contributing to resistance were estimated by generation means analyses. Additive gene action was the most important genetic component of variation among generation means in all four crosses. Additive by additive effects were significant in one cross and both additive by additive and additive by dominance effects were significant in another. Dominance effects were not significant. The F2/F3 correlations in three crosses ranged from 0.27 to 0.43. Three additional crosses among resistant cultivars were employed to study the effectiveness of selection in improving resistance. By selecting the most resistant plants from the F2 and evaluating the progenies in the F4, increases in resistance ranging from 21% to 31% were obtained. In all crosses, there was transgressive segregation in both directions indicating that the genes conferring resistance to these cultivars differ and exhibit additive effects. PMID- 24241122 TI - The origin and genetic diversity of Pinus radiata in Australia. AB - Despite the fact that forest trees are in early stages of domestication there has been little direct evaluation of either the origin of, or genetic diversity within the breeding material in tree improvement programs. Allozyme variation was used to compare the total genetic diversity in the breeding programs of P. radiata within Australia and the five wild populations in North America. The current breeding populations were very similar genetically and were essentially homogenous with only 1.8% of the variation among programs. The total genetic diversity in the species was 0.12, which is a low estimate compared to most conifers. Overall in the Australian material the genetic diversity was somewhat less. The comparison of allelic frequencies in the five native populations with the Australian material indicates that the Monterey and Ano Nuevo populations were probably the major source of the original introductions and that a substantial portion of the genetic diversity in the two populations has been captured in current breeding programs. The three southern populations do not appear to be currently represented in the breeding programs. The implications for future breeding strategies are discussed. PMID- 24241123 TI - Prospective 5-year survival rate data following open-wedge valgus high tibial osteotomy. AB - PURPOSE: Open-wedge high tibial osteotomy using internal plate fixation is a well established and frequently performed treatment option for the management of medial compartment osteoarthritis (OA) in the young and active patients. The present study provides survival rate and functional outcome preoperatively and after 6, 12, 24, 36 and 60 months following open-wedge high tibial osteotomy. Hypothesis of the authors was high survival rates after 5 years with still remaining satisfying functional results. METHODS: Sixty-two patients suffering from tibial conditioned knee joint varus deformity and medial compartment OA that underwent high tibial osteotomy using an internal plate fixator (TomoFixTM, Synthes) were included. Functional outcome was evaluated prior to surgery and in the further clinical course using standard instruments (IKDC score, Lysholm score). Treatment failure was defined as the need for total knee arthroplasty (TKA). RESULTS: Fifty-one patients (mean age 46.8 +/- 10.2 years) were available at a mean of 60.5 (SD +/- 2.5) months (follow-up rate 82.3 %) postoperatively. Sixty-month IKDC (69.4 % SD +/- 18.6) and Lysholm (76.6 SD +/- 20.5) improved significantly when comparing with preoperative values (IKDC 44.6 SD +/- 17.8; Lysholm 52.1 SD +/- 20.8). Two of 51 subjects underwent TKA, resulting in a survival rate of 96 % among those patients followed (51 of 60; 85 %). Overall complication rate was 8.6 %. CONCLUSION: With a survival rate of over 96 % at 5 years, high tibial osteotomy seems to be a reliable treatment option with satisfying clinical outcome. Functional outcome was stable following 60 months. While a delay of the necessity for TKA seems likely with regard to the survival rate demonstrated in this article, possible avoidance needs to be demonstrated by longer follow-up studies. LEVEL OF EVIDENCE: Therapeutic case series, Level IV. PMID- 24241125 TI - Multiplex PCR for diagnosis of Theileria uilenbergi, Theileria luwenshuni, and Theileria ovis in small ruminants. AB - Infections with Theileria sp. may cause significant economic losses to the sheep industry. Species identification based on microscopic examination is difficult, and more suitable methods are required for the rapid detection and identification of Theileria sp, in clinical specimens. In this study, a multiplex polymerase chain reaction (mPCR) assay was developed to simultaneously identify three individual Theileria species in small ruminants. Three pairs of specific, sensitive primers were designed on the basis of the 5.8S ribosomal RNA gene (Theileria luwenshuni and Theileria ovis) and the 18S ribosomal RNA gene (Theileria uilenbergi) to generate target products of 303, 884, and 530 bp, respectively. Standard DNA for each of the three species was extracted from blood recovered from infected sheep, and a preliminary study was conducted on 56 sheep to verify the reliability of the system. Optimal PCR conditions, including primer concentration, annealing time, and the number of amplification cycles, were established. The assay sensitivity under these conditions was 10(-3) % parasitemia, and its specificity was 100 %. The results of the study suggest that mPCR represents a simple, efficient test method as a practical alternative for the rapid detection and identification of Theileria species in small ruminants. PMID- 24241126 TI - Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis. AB - In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2-3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1-41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8-88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis. PMID- 24241124 TI - Extracellular vesicles shed by Trypanosoma cruzi are linked to small RNA pathways, life cycle regulation, and susceptibility to infection of mammalian cells. AB - The protozoan parasite Trypanosoma cruzi has a complex life cycle characterized by intracellular and extracellular forms alternating between invertebrate and mammals. To cope with these changing environments, T. cruzi undergoes rapid changes in gene expression, which are achieved essentially at the posttranscriptional level. At present, expanding families of small RNAs are recognized as key players in novel forms of posttranscriptional gene regulation in most eukaryotes. However, T. cruzi lacks canonical small RNA pathways. In a recent work, we reported the presence of alternate small RNA pathways in T. cruzi mainly represented by a homogeneous population of tRNA-derived small RNAs (tsRNAs). In T. cruzi epimastigotes submitted to nutrient starvation, tsRNAs colocalized with an argonaute protein distinctive of trypanosomatids (TcPIWI tryp) and were recruited to particular cytoplasmic granules. Using epifluorescence and electronic microscopy, we observed that tsRNAs and the TcPIWI tryp protein were recruited mainly to reservosomes and other intracellular vesicles including endosome-like vesicles and vesicular structures resembling the Golgi complex. These data suggested that, in T. cruzi, tsRNA biogenesis is probably part of endocytic/exocytic routes. We also demonstrated that epimastigotes submitted to nutrient starvation shed high levels of vesicles to the extracellular medium, which carry small tRNAs and TcPIWI-tryp proteins as cargo. At least a fraction of extracellular vesicle cargo was transferred between parasites and to mammalian susceptible cells. Our data afford experimental evidence, indicating that extracellular vesicles shed by T. cruzi promote not only life cycle transition of epimastigotes to trypomastigote forms but also infection susceptibility of mammalian cells. PMID- 24241127 TI - Computational investigation on redox-switchable nonlinear optical properties of a series of polycyclic p-quinodimethane molecules. AB - The polycyclic p-quinodimethanes are proposed to be the novel candidates of the high-performance nonlinear optical (NLO) materials because of their large third order polarizabilities (gamma). We investigate the switchable NLO responses of a series of polycyclic p-quinodimethanes with redox properties by employing the density functional theory (DFT). The polycyclic p-quinodimethanes are forecasted to exhibit obvious pure diradical characters because of their large y 0 index (the y 0 index is a value between 0 [closed-shell state] and 1 [pure biradical state]). The gamma values of these polycyclic p-quinodimethanes and their corresponding one-electron and two-electron reduced/oxidized species are calculated by the (U)BHandHLYP method. The gamma values of polycyclic p quinodimethanes and their corresponding one-electron reduced species are all positive and significantly different. The large differences of the gamma values are due to a change in the transition energy and are related to the different delocalization of the spin density, which demonstrates that the NLO switching is more effective on one-electron reduction reactions. Therefore, the study on these polycyclic p-quinodimethanes provides a guideline for a molecular design of highly efficient NLO switching. PMID- 24241129 TI - Antioxidant supplements and mortality. AB - PURPOSE OF REVIEW: Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high income countries. This has stimulated interest in the preventive potential of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging. RECENT FINDINGS: Older observational studies and some randomized clinical trials with high risks of systematic errors ('bias') have suggested that antioxidant supplements may improve health and prolong life. A number of randomized clinical trials with adequate methodologies observed neutral or negative results of antioxidant supplements. Recently completed large randomized clinical trials with low risks of bias and systematic reviews of randomized clinical trials taking systematic errors ('bias') and risks of random errors ('play of chance') into account have shown that antioxidant supplements do not seem to prevent cancer, cardiovascular diseases, or death. Even more, beta-carotene, vitamin A, and vitamin E may increase mortality. Some recent large observational studies now support these findings. According to recent dietary guidelines, there is no evidence to support the use of antioxidant supplements in the primary prevention of chronic diseases or mortality. SUMMARY: Antioxidant supplements do not possess preventive effects and may be harmful with unwanted consequences to our health, especially in well nourished populations. The optimal source of antioxidants seems to come from our diet, not from antioxidant supplements in pills or tablets. PMID- 24241131 TI - The rhetoric and reality of e-health: a critical assessment of the benefits of e health in primary health care. PMID- 24241133 TI - Amyloplast sedimentation kinetics in gravistimulated maize roots. AB - Amyloplast sedimentation in gravistimulated maize (Zea mays L.) roots was measured using the change in angle from the center of the cell to each amyloplast as an index of sedimentation. Using tissue fixed after gravistimulation, the relationship between mean amyloplast angle and the duration of gravistimulation was found to be linear when plotted on a logarithmic time scale. Extrapolated values for the onset of angular change are 5.9 s after the start of gravistimulation for the entire population of amyloplasts and 11.8 s for lead amyloplasts. By multiplying the instantaneous angular velocity (in radians) by the cell center to amyloplast radius, it is possible to calculate the initial sedimentation velocity to be 19.1 MUm min(-1) at 5.9 s. During sedimentation, the mean amyloplast angles surpass the calculated cell corner angle of 123 degrees at 2.2 min for all amyloplasts and at 19 s for lead amyloplasts near the new lower wall. Thus, substantial sedimentation occurs within the presentation time, calculated to be 4.1 min. These kinetics are consistent with several hypotheses of graviperception. PMID- 24241134 TI - Calcium-induced patterns of calcium-oxalate crystals in isolated leaflets of Gleditsia triacanthos L. and Albizia julibrissin Durazz. AB - For experimental induction of crystal cells (=crystal idioblasts) containing calcium-oxalate crystals, the lower epidermis was peeled from seedling leaflets of Gleditsia triacanthos L., exposing the crystal-free mesophyll and minor veins to the experimental solutions on which leaflets were floated for up to 10 d under continous light. On 0.3-2.0 mM Ca-acetate, increasing numbers of crystals, appearing 96 h after peeling, were induced. The pattern of crystal distribution changed with Ca(2+)-concentration ([Ca(2+)]): at low [Ca(2+)], crystals formed only in the non-green bundlesheath cells surrounding the veins, believed to have a relatively low Ca(2+)-extrusion capacity; at higher [Ca(2+)], crystals developed in up to 90% of the mesophyll cells, and at supraoptimal [Ca(2+)], large extracellular crystals formed on the tissue surface. By sequential treatments with solutions of different [Ca(2+)], the following three phases were identified in the induction of crystal cells: (1) during the initial 24-h period (adaptive aging), Ca(2+) is not required and crystal induction is not possible; (2) during the following 48 h (induction period), exposure to 1-2 mM Ca-acetate induces the differentiation of mesophyll cells into crystal cells; (3) crystal growth begins 72 h after the start of induction. In intact leaflets of Albizia julibrissin Durazz., calcium-oxalate crystals are found exclusively in the bundle sheath cells of the veins, but crystals were induced in the mesophyll of peeled leaflets floating on 1 mM Ca-acetate. Exposure to inductive [Ca(2+)] will thus trigger the differentiation of mature leaf cells into crystal cells; the spatial distribution of crystals is determined by the external [Ca(2+)] and by the structural and functional properties of the cells in the tissue. PMID- 24241135 TI - Tagetitoxin affects plastid development in seedling leaves of wheat. AB - Ultrastructural and biochemical approaches were used to investigate the mode of action of tagetitoxin, a nonhost-specific phytotoxin produced by Pseudomonas syringae pv. tagetis (Hellmers) Young, Dye and Wilkie, which causes chlorosis in developing - but not mature - leaves. Tagetitoxin has no effect on the growth rate or morphology of developing leaves of wheat (Triticum aestivum L.) seedlings. Its cytological effects are limited to plastid aberrations; in both light-and dark-grown leaves treated with toxin, internal plastid membranes fail to develop normally and plastid ribosomes are absent, whereas mitochondrial and cytoplasmic ribosomes are unaffected. The activity of a plastid stromal enzyme, ribulose-1,5-bisphosphate carboxylase (RuBPCase, EC 4.1.1.39), which is co-coded by nuclear and chloroplast genes, is markedly lower in extracts of both light-and dark-grown toxin-treated leaves, whereas the activity of another stromal enzyme, NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-G-3P-DH, EC 1.2.1.13), which is coded only by the nuclear genome, is significantly lower in extracts of light grown, but not of dark-grown, treated leaves. The mitochondrial enzymes fumarase (EC 4.2.1.2) and cytochrome-c oxidase (EC 1.9.3.1) are unaffected by toxin in dark-grown leaves, but fumarase activity is reduced in light-grown ones. Four peroxisomal enzyme activities are lowered by toxin treatment in both light- and dark-grown leaves. Light- and dark-grown, toxintreated leaves contain about 50% and 75%, respectively, of the total protein of untreated leaves. There are threefold and twofold increases in free amino acids in light-grown and dark-grown treated leaves, respectively. In general, the effects of tagetitoxin are more extensive and exaggerated in light-grown than in dark-grown leaves. We conclude that tagetitoxin interferes primarily with a light-independent aspect of chloroplast-specific metabolism which is important in plastid biogenesis. PMID- 24241136 TI - The production of callus capable of plant regeneration from immature embryos of numerous Zea mays genotypes. AB - In the summer of 1983, immature embryos from 101 selfed inbred lines and germplasm stocks of Zea mays L. were examined for their ability to produce callus cultures capable of plant regeneration (regenerable cultures) using a medium with which some limited success had previously been obtained. Forty-nine of the genotypes (49%) produced callus which visually appeared similar to callus previously cultured and shown to be capable of plant regeneration. After five months, 38 of these genotypes were alive in culture and plants were subsequently regenerated from 35 (92%) of them. No correlation was observed between plant regeneration and callus growth rate, the vivipary mutation (genes vp1, 2, 5, 7, 8 and 9), or published vigor ratings based on K(+) uptake by roots. When F1 hybrid embryos were cultured, 97% of the hybrids having at least one regenerable parent also produced callus capable of plant regeneration. No regenerable cultures were obtained from any hybrid lacking a parent capable of producing a regenerable callus culture.In the summer of 1984, immature embryos from 218 additional inbred lines and germplasm stocks were plated and examined for their ability to produce regenerable callus cultures on media containing altered micronutrient concentrations, 3,6-dichloro-o-anisic acid (dicamba), glucose, and elevated levels of vitamin-free casamino acids and thiamine. Of these genotypes 199 (91%) produced callus that was regenerable in appearance. In the 1984 study, plant regeneration was noted in many commercially important inbreds, including B73, Mo17, B84, A632, A634, Ms71, W117, H99(3)H95 and Cm105. Thus tissue-culture techniques are now available to obtain callus cultures capable of plant regeneration from immature embryos of most maize genotypes. PMID- 24241137 TI - Immuno-gold localization of cytochrome f, light-harvesting complex, ATP synthase and ribulose 1,5-bisphosphate carboxylase/oxygenase. AB - The proteins ribulose 1,5-bisphosphate carboxylase/oxygenase, ATP synthase, light harvesting chlorophyll a/b protein, and cytochrome f, have been localized in mesophyll chloroplasts of barley (Hordeum vulgare L.) by electron microscopy of immunogold-labelled sections. The light-harvesting chlorophyll a/b protein and cytochrome f are shown to be present in the grana, both within the stacks and at the margins, and in the stromal membranes. Although the absolute amount of labelling for these proteins is greater in the grana than in the stromal membranes, when expressed as label/membrane length the partitioning appears approximately equal between appressed and non-appressed membranes for both the light-harvesting chlorophyll a/b protein and cytochrome f. ATP synthase is restricted to the non-appressed thylakoid membranes, and ribulose 1,5 bisphosphate carboxylase/oxygenase is uniformly distributed through the stromal contents. PMID- 24241138 TI - A Chlamydomonas reinhardii mutant with catalytically and structurally altered ribulose-5-phosphate kinase. AB - The biochemical lesion in a light-sensitive, acetate-requiring Chlamydomonas mutant was identified. This strain, designated rpk, exhibited photosynthetic rates less than 3% of the wild-type. Analysis of photosynthetic products by high performance liquid chromatography demonstrated an accumulation of (14)C label in pentose and hexose monophosphates. After 1 min of photosynthesis in (14)CO2 these intermediates comprised 27.5% of the label in the mutant compared with 8% in the wild-type. The mutant pheno-type was caused by a 20-fold reduction in ribulose-5 phosphate (Ru5P)-kinase (EC 2.7.1.19) activity. The mutant exhibited wild-type levels of ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39), fructose-1,6 bisphosphate aldolase (EC 4.1.2.13) and transketolase (EC 2.2.1.1) indicating that the mutation specifically affected Ru5P kinase. In a cross of the mutant with the wild-type, tetrad progeny segregated in a Mendelian fashion (1:1) and light-sensitivity cosegregated with reduced Ru5P-kinase activity and an acetate requirement for growth. Almost normal levels of Ru5P-kinase protein were detected in the mutant by probing nitrocellulose replicas of sodium dodecylsulfate polyacrylamide gels with anti-Ru5P-kinase antibody. The subunit size of the mutant enzyme, 42 kDa, was identical to that of the wild-type. Isoelectric focusing of the native protein determined that the mutant protein was altered, exhibiting a more acidic isoelectric point than the wild-type protein. Thus, the molecular basis for the lesion affecting Ru5P-kinase activity in mutant rpk is a charge alteration which results in a partially impaired enzyme. PMID- 24241139 TI - beta-Glucan biosynthesis in synchronous cells of Prototheca zopfii. AB - Synchronous cultures of the colorless chlorophyte Prototheca zopfii Kruger were obtained by a shift-down of the basal medium plus addition of 1.5 mM ethylenediaminetetracetic acid for a 10-14-h period, followed by periodic dilutions with the basal medium. The cell cycle has a duration of 10-12 h at 25 degrees C and an average of eight autospores are produced at the end of each cycle. The incorporation of [(14)C]glucose into beta-glucans was determined in vivo. Very high incorporation occurs between hours 3 and 4 of culture, coincident with maximal cell expansion. The incorporation of glucose from uridine 5'diphospho-[(14)C]glucose into lipid-linked sugars and glycoproteins, as well as the activity of guanosine 5'-diphosphoglucose:beta-glucan synthase found in cell free preparations are in good agreement with the in-vivo incorporation of glucose into beta-glucans. PMID- 24241140 TI - Induction of budding on chloronemata and caulonemata of the moss, Physcomitrella patens, using isopentenyladenine. AB - The bud-inducing effect of the cytokinin N(6)-(Delta(2)-isopentenyl)-adenine (i(6)-Ade) was examined in the moss Physcomitrella patens growing in liquid culture. Under these conditions, buds could be induced on chloronemata as well as on caulonemata. By application of i(6)-Ade, bud-formation was accelerated in both types of tissue. The number of buds, their size and their site of development were dependent on the concentration of the cytokinin in the range of 10(-7) M to 10(-5) M. Moreover, the percentage of caulonema cells increased with a cytokinin concentration of 10(-5) M. These results indicate that chloronema cells may also function as target cells for exogenous cytokinins. The composition of proteins from caulonemata and chloronemata of two different species (P. patens and Funaria hygrometrica), grown on solid medium were compared. No differences could be detected between the protein patterns of caulonemata and chloronemata of the same species while between the two species the differences were obvious. PMID- 24241141 TI - The control of bud dormancy in potato tubers : Evidence for the primary role of cytokinins and a seasonal pattern of changing sensitivity to cytokinin. AB - Potato (Solanum tuberosum L.) tuber buds normally remain dormant through the growing season until several weeks after harvest. In the cultivar Majestic, this innate dormancy persisted for 9 to 12 weeks in storage at 10 degrees C, but only 3 to 4 weeks when the tubers were stored at 2 degrees C. At certain stages, supplying cytokinins to tubers with innately dormant buds induced sprout growth within 2 d. The growth rate was comparable to that of buds whose innate dormancy had been lost naturally. Cytokinin-treatment did not accelerate the rates of cell division and cell expansion in buds whose innate dormancy had already broken naturally. Gibberellic acid did not induce sprout growth in buds with innate dormancy. We conclude that cytokinins may well be the primary factor in the switch from innate dormancy to the non-dormant state in potato tuber buds, but probably do not control the subsequent sprout growth. PMID- 24241142 TI - The control of bud dormancy in potato tubers. Measurement of the seasonal pattern of changing concentrations of zeatin-cytokinins. AB - A radioimmunoassay, combined with high-performance liquid chromatography, has been used to analyse the zeatin-type cytokinins of potato (Solanum tuberosum L. cv. Majestic) tubers and tuber buds throughout growth and storage. During tuber growth, zeatin riboside was the predominant cytokinin detected in all tissues. Immediately after harvest, the total cytokinin concentration fell dramatically in the storage tissue, largely as a consequence of the disappearance of zeatin riboside. During storage, levels of cytokinins in the storage tissue remained relatively constant, but increased in the tuber buds. In the buds of tubers stored at 2 degrees C there was a 20-to 50-fold increase in total cytokinin over six weeks, coinciding with the natural break of innate dormancy. At 10 degrees C the rise in the level of bud cytokinins was slower, correlating with the longer duration of innate dormancy. Injecting unlabelled cytokinins into tubers in amounts known to induce sprouting gave rise to increases in cytokinin concentrations in the buds of the same order as the increase associated with the natural break of dormancy. Metabolism of injected cytokinins was greater in non dormant than in dormant tubers. The roles of cytokinin concentration and the sensitivity of the buds to cytokinin in the control of dormancy are discussed. PMID- 24241143 TI - Appearance of wheat-germ agglutinin during maturation of field-grown wheat. AB - Field-grown wheat (Triticum aestivum L.) has been used as a developmental system to study the appearance of wheat-germ agglutinin during grain maturation. The lectin appears at the mid-grain growth period (30-34 days post-anthesis) and continues to be synthesised throughout the late stages of maturation and desiccation. An acidic endopeptidase activity, inhibited by pepstatin phenanthroline is present in extracts of embryo and endosperm throughout maturation. After in-vivo labelling of immature embryos with [(35)S]methionine for 3 h and extraction in the presence of proteinase inhibitors, immunoprecipitates with anti-wheat-germ agglutinin were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, and found to contain three (35)S-labelled polypeptides of Mr 46000, 18000 and 13000. Comparison of two-dimensional tryptic maps of (125)I-labelled peptides indicate the three polypeptides are closely related. PMID- 24241144 TI - Evidence for electron transport across the plasma membrane of Zea mays root cells. AB - Exogenous ferricyanide is reduced by roots of Z. mays. In contrast to oxidation of exogenous electron donors, ferricyanide reduction occurs mostly at the apical 5 mm of the root. Using just this portion of the root, it is shown that the activity is neither a consequence of uptake of ferricyanide followed by excretion of its reduced form, nor of leakage of a reductant. Addition of ferricyanide for 40 s or 5 min results in an apparent oxidation of NADPH but not of NADH; rates of ferricyanide reduction vary together with levels of NADPH but not of NADH in the presence or absence of oxygen. It is concluded that an enzyme which can oxidize cytoplasmic NADPH and transfer the electrons to an external acceptor exists at the cell surface of maize roots. This finding extends the results of others who showed similar redox activity at the surface of Fe-depleted dicotyledonous roots, and indicates that an energy source other than ATP exists at the cell surface of a variety of plants under unstressed conditions. PMID- 24241145 TI - Salt tolerance in the halophyte Suaeda maritima L. Dum. : The maintenance of turgor pressure and water-potential gradients in plants growing at different salinities. AB - Osmotic potentials and individual epidermal cell turgor pressures were measured in the leaves of seedlings of Suaeda maritima growing over a range of salinities. Leaf osmotic potentials were lower (more negative) the higher the salt concentration of the solution and were lowest in the youngest leaves and stem apices, producing a gradient of osmotic potential towards the apex of the plant. Epidermal cell turgor pressures were of the order of 0.25 to 0.3 MPa in the youngest leaves measured, decreasing to under 0.05 MPa for the oldest leaves. This pattern of turgor pressure was largely unaffected by external salinity. Calculation of leaf water potential indicated that the gradient between young leaves and the external medium was not altered by salinity, but with older leaves, however, this gradient diminished from being the same as that for young leaves in the absence of NaCl, to under 30% of this value at 400 mM NaCl. These results are discussed in relation to the growth response of S. maritima. PMID- 24241146 TI - Effect of temperature on the CO2/O 2 specificity of ribulose-1,5-bisphosphate carboxylase/oxygenase and the rate of respiration in the light : Estimates from gas-exchange measurements on spinach. AB - Responses of the rate of net CO2 assimilation (A) to the intercellular partial pressure of CO2 (p i ) were measured on intact spinach (Spinacia oleracea L.) leaves at different irradiances. These responses were analysed to find the value of p i at which the rate of photosynthetic CO2 uptake equalled that of photorespiratory CO2 evolution. At this CO2 partial pressure (denoted G), net rate of CO2 assimilation was negative, indicating that there was non photorespiratory CO2 evolution in the light. Hence G was lower than the CO2 compensation point, Gamma. Estimates of G were obtained at leaf temperatures from 15 to 30 degrees C, and the CO2/O2 specificity of ribulose 1,5-bisphosphate (RuBP) carboxylase/oxygenase (E.C. 4.1.1.39) was calculated from these data, taking into account changes in CO2 and O2 solubilities with temperature. The CO2/O2 specificity decreased with increasing temperature. Therefore we concluded that temperature effects on the ratio of photorespiration to photosynthesis were not solely the consequence of differential effects of temperature on the solubilities of CO2 and O2. Our estimates of the CO2/O2 specificity of RuBP carboxylase/oxygenase are compared with in-vitro measurements by other authors. The rate of nonphotorespiratory CO2 evolution in the light (R d ) was obtained from the value of A at G. At this low CO2 partial pressure, R d was always less than the rate of CO2 evolution in darkness and appeared to decrease with increasing irradiance. The decline was most marked up to about 100 MUmol quanta m(-2) s(-1) and less marked at higher irradiances. At one particular irradiance, however, R d as a proportion of the rate of CO2 evolution in darkness was similar in different leaves and this proportion was unaffected by leaf temperature or by [O2] (ambient and greater). After conditions of high [CO2] and high irradiance for several hours, the rate of CO2 evolution in darkness increased and R d also increased. PMID- 24241147 TI - Stimulation of extracellular polysaccharide synthesis in oat protoplasts by the host-specific phytotoxin victorin. AB - The host-specific phytotoxin victorin (HV-toxin) stimulates mesophyll protoplasts of susceptible but not of resistant oat (Avena sativa L.) to produce an amorphous, ethanol-insoluble extracellular material which stains with Calcofluor white and aniline blue. Over a 24-h period incorporation of [(14)C]glucose into ethanol-insoluble products is maximally stimulated by 60 pg victorin/ml, whereas at 6 ng/ml initial rates of incorporation are higher but the protoplasts collapse. The extracellular material produced in response to victorin is solubilized by cold 4.4 N NaOH and by commercial laminarinase and pectinase. Incorporation of [(14)C]glucose into cellulose (material resistant to Updegraff's acetic-nitric acid reagent) is stimulated as much as incorporation into other wall polysaccharides, but cellulose constitutes less than 15% of the total victorin-stimulated incorporation. Synthesis of ethanol-insoluble material that can be digested by pronase, i.e. protein, is inhibited by victorin above 60 pg victorin/ml. Formation of extracellular polysaccharide is stimulated at concentrations of victorin which cause almost complete inhibition of protein synthesis, indicating that de-novo protein synthesis is not involved. Preincubation of protoplasts with inhibitors of RNA or protein synthesis prevents both extracellular polysaccharide synthesis and cell death in response to victorin. Although previous studies have indicated a link between calcium and the action of victorin, several compounds which interact with calcium do not influence this response to victorin. PMID- 24241148 TI - Metabolite levels in the stroma of spinach chloroplasts exposed to osmotic stress: Effects of the pH of the medium and exogenous dihydroxyacetone phosphate. AB - The levels of stromal photosynthetic intermediates were measured in isolated intact spinach (Spinacia oleracea L.) chloroplasts exposed to reduced osmotic potentials. Stressed chloroplasts showed slower rates of metabolite accumulation upon illumination than controls. Relative to other metabolites sedoheptulose-1,7 bisphosphate (SBP) and fructose-1,6-bisphosphate (FBP) accumulated in the stroma in the stressed treatments. Under these conditions 3-phosphoglycerate (3-PGA) efflux to the medium was restricted. Chloroplasts previously incubated with [(32)P]KH2PO4 and [(32)P]dihydroxyacetone phosphate ([(32)P]DAP) in the dark were characterized by very high FBP and SBP levels prior to illumination. Metabolism of these pools upon illumination increased with increasing pH of the medium but was consistently inhibited in osmotically stressed chloroplasts. The responses of stromal FBP and SBP pools under hypertonic conditions are discussed in terms of both inhibited light activation of fructose-1,6-bisphosphatase (EC 3.1.3.11) and sedoheptulose-1,7-bisphosphatase (EC 3.1.3.37), and likely increases in stromal ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) active-site concentrations. PMID- 24241149 TI - Phytochrome-mediated phototropism in maize mesocotyls. Relation between light and Pfr gradients, light growth response and phototropism. AB - Unilateral irradiation of maize (Zea mays L.) seedlings results in a fluence-rate gradient, and hence below saturation, a gradient of the far-red-absorbing form of phytochrome (Pfr). The Pfr-gradients established by blue, red and far-red light were spectrophotometrically measured in the mesocotyl. Based on these Pfr gradients and the fluence-response curves of phytochrome photoconversion the fluence-rate gradients were calculated. The fluence-rate gradient in the blue (460 nm) was steeper than that in the red (665 nm), which in turn was steeper than that in the far-red light (725 nm). The fluence-rate ratios front to rear were 1:0.06 (460 nm), 1:0.2 (665 nm), and 1:0.33 (725 nm). The assumption that phytochrome-mediated phototropism of maize mesocotyls is caused by local phytochrome-mediated growth inhibition was tested in the following manner. Firstly, the Pfr response curve for growth inhibition was calculated; these calculations were based on measurements of Pfr-gradients and data from red-light induced phototropism. Secondly, the Pfr response curve for growth inhibition was used as a basis for calculating fluence-response curves for blue-and far-red light-induced phototropism. Finally, these calculated results were compared with experimental data. It was concluded that the threshold for phytochrome-mediated phototropism of maize mesocotyls reflects the apparent photoconversion cross section of phytochrome whereas the maximal inducable curvature depends on the steepness of the light (Pfr) gradient across the mesocotyl. PMID- 24241151 TI - Erratum. PMID- 24241150 TI - Photoinhibition of photosynthesis under anaerobic conditions studied with leaves and chloroplasts of Spinacia oleracea L. AB - The role of oxygen in the photoinactivation of the photosynthetic apparatus of Spinacia oleracea L. was investigated. Moderate irradiation (1200 MUmol photons m(-2)s(-1)) of spinach leaves in an atmosphere of pure nitrogen caused strong inhibition of subsequently measured net CO2 assimilation, whereas considerably less photoinhibition was observed in the presence of low partial pressures (10-20 mbar) of O2. The decrease in activity caused by anaerobiosis in the light was not based on stomatal closure; the decline of assimilation represents a photoinhibition, as activity was not impaired by low irradiation (80 MUmol photos m(-2)s(-1)). In contrast, gassing with pure N2 in the dark caused strong inhibition. Electron-transport rates and chlorophyll-fluorescence data of thylakoids isolated from photoinhibited leaves indicated damage to the electron transport system, in particular to photosystem II reaction centers. In vitro, photoinhibition in isolated thylakoid membranes was also strongly promoted by anaerobiosis. Photoinhibition of electron-transport rates under anaerobic conditions was characterized by a pronounced increase in the initial fluorescence level, F0, of chlorophyll-fluorescence induction, in contrast to photoinhibition under aerobic conditions. The results are discussed in terms of two mechanisms of photoinhibition, one that is suppressed and a second that is promoted by oxygen. PMID- 24241152 TI - The histone deacetylase inhibitors MS-275 and SAHA suppress the p38 mitogen activated protein kinase signaling pathway and chemotaxis in rheumatoid arthritic synovial fibroblastic E11 cells. AB - MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK) signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38alpha MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1), an endogenous suppressor of p38alpha in E11 cells. At the same time, the association between p38alpha and MKP-1 was up-regulated and consequently, the activation (phosphorylation) of p38alpha was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2), monocyte chemotactic protein-2 (MCP-2) and macrophage migration inhibitory factor (MIF) in E11 cells in a concentration dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors. PMID- 24241153 TI - Bioactive quinic acid derivatives from Ageratina adenophora. AB - A novel quinic acid derivative, 5-O-trans-o-coumaroylquinic acid methyl ester (1), together with three known ones, chlorogenic acid methyl ester (2), macranthoin F (3) and macranthoin G (4), were isolated from the aerial parts of the invasive plant Ageratina adenophora (Spreng.). The structure of new compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 2-4 were isolated from plant A. adenophora for the first time. All the compounds showed in vitro antibacterial activity toward five assayed bacterial strains, especially 3 and 4, which showed in vitro antibacterial activity against Salmonella enterica with MIC values of 7.4 and 14.7 MUM, respectively. Compound 1 was further found to display in vitro anti fungal activity against spore germination of Magnaporthe grisea with an IC50 value 542.3 uM. These four compounds were also tested for their antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. PMID- 24241154 TI - Chemical composition and antioxidant activity of Tanara Oto (Dracocephalum palmatum Stephan), a medicinal plant used by the North-Yakutian nomads. AB - Dracocephalum palmatum Stephan (Lamiaceae) is a medicinal plant used by the North Yakutian nomads. From the crude ethanolic extract of the aerial parts of this plant, 23 compounds (phenylpropanoids, coumarins, flavonoids, and triterpenes) were isolated. Among these, eight compounds (salvianolic acid B, caftaric acid, cichoric acid, umbelliferone, aesculetin, apigenin-7-O-beta-D glucuronopyranoside, isorhoifolin, and luteolin-4'-O-beta-D-glucopyranoside) were detected for the first time in the genus Dracocephalum. Their structures were elucidated based on chemical and spectral data. The levels of most of the compounds detected in the cultivated sample were close to that of the wild sample, indicating the reproducibility of the biologically active compounds of D. palmatum through cultivation. Investigation into the biological activity of D. palmatum under in vitro conditions demonstrated that its extracts have a strong antioxidant effect due to the presence of high concentrations of phenolic compounds. PMID- 24241155 TI - Polymeric systems of antimicrobial peptides--strategies and potential applications. AB - The past decade has seen growing interest in the investigation of peptides with antimicrobial activity (AMPs). One approach utilized in infection control is incorporation of antimicrobial agents conjugated with the polymers. This review presents the recent developments on polymeric AMP carriers and their potential applications in the biomedical and pharmaceutical fields. PMID- 24241156 TI - Three new germacrane-type sesquiterpenes with NGF-potentiating activity from Valeriana officinalis var. latiofolia. AB - Three new germacrane-type sesquiterpenoids, volvalerenal F (1), volvalerenal G (2) and volvalerenic acid D (3), along with five known compounds 4-8, were isolated from the CHCl3 soluble partition of the ethanol extract of Valeriana officinalis var. latiofolia. The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, as well as mass spectrometry. The eight germacrane-type sesquiterpenoids showed nerve growth factor (NGF) potentiating activity, which mediates the neurite outgrowth in PC 12D cells. This study intends to reveal the chemical basis of the use of V. officinalis var. latiofolia as a dietary supplement. PMID- 24241158 TI - Effects of light intensity, oxygen concentration, and carbon dioxide concentration on photosynthesis in algae. AB - The effects of various combinations of light intensity, oxygen concentration, and CO2 concentration on photosynthesis and growth in several algal types were studied. The results suggest the following. (1) Different algae show different responses to high oxygen concentrations and high light intensities. (2) Inhibition of photosynthesis (CO2 fixation and growth), if seen, increases with increasing oxygen concentration and with increasing light intensity (at light intensities greater than saturation). (3) The inhibition of net photosynthesis observed cannot be attributed to high light intensity alone. (4) The inhibition cannot be attributed to increased rates of excretion of organic materials under conditions of high oxygen concentration and high light intensity. (5) Increased concentrations of CO2 can decrease the effect of high oxygen and light in some algae. (6) The decrease in net photosynthesis observed is probably the result of photorespiration. (7) The effect of light intensity, oxygen concentration, or CO2 concentration on algal photosynthesis should not be studied without considering the effect of the other factors. Some implications of these results, as related to primary productivity measurements, are also discussed. PMID- 24241157 TI - Management and treatment goals in Polish patients with type 2 diabetes of short duration: results of the ARETAEUS2-Grupa study. AB - INTRODUCTION: In 2011, the Diabetes Poland updated its recommended goals in diabetes treatment, including hemoglobin A1c (HbA1c) and blood pressure (BP) levels. Adherence to the updated guidelines has not been systematically assessed so far. OBJECTIVES: The aim of the study was to assess which methods are most commonly used in the treatment of recently diagnosed type 2 diabetes and to what extent the new criteria for diabetes control are met in these patients. PATIENTS AND METHODS: The ARETAEUS2-Grupa study was a cross-sectional questionnaire-based study conducted in Poland in 2012 (April-June). It involved 1636 patients of any age and sex, with type 2 diabetes diagnosed within the previous 2 years, recruited by randomly selected physicians. RESULTS: Of all patients, 37.5% met the goal of an HbA1c level of <=6.5% (recommended in type 2 diabetes of short duration), while 62% met the goal of an HbA1c level of <=7% (general recommendation). Only 6.7% of the patients met all 3 goals (HbA1c <=6.5%, BP <140/90 mmHg, and low-density lipoprotein cholesterol <100 mg/dl or <70 mg/dl in coronary heart disease), 29.7% met 2 goals, 36.8% met only 1 goal, while 26.7% did not meet any of the treatment goals. With the use of the HbA1c level recommended for the overall population, the proportions of patients meeting 3, 2, and 1 goals increased to 11%, 34.5%, and 35.5%, respectively, while the percentage of the patients not meeting any goals decreased to 18%. Metformin in monotherapy or in combination was the most commonly used drug in the study population (80%). CONCLUSIONS: The majority of the patients with type 2 diabetes of short duration did not meet any of the treatment goals as recommended in the current practice guidelines. When the treatment goals were used for the overall population (HbA1c <=7%), a slightly higher, but still unsatisfactory, proportion of the patients met all the treatment goals. Metformin alone or in combination was the most commonly used drug in the study population. PMID- 24241159 TI - Environmental and microbiological problems arising from recalcitrant molecules. PMID- 24241160 TI - A radioisotope assay for the quantification of hydrocarbon biodegradation potential in environmental samples. AB - An enrichment culture method is described for quantifying the activity of hydrocarbon oxidizing bacteria in water and sediments. Application of the procedure indicated that the hydrocarbon oxidizing potential of environmental samples reflects the hydrocarbon burden of the area, the ability of the microflora to utilize hydrocarbons, and that lakes with large aquatic plant communities contain populations of hydrocarbon bacteria comparable to those found in oil-polluted harbors. PMID- 24241161 TI - Bacterial bioconcentration of chlorinated hydrocarbon insecticides from aqueous systems. AB - The prevalence of chlorinated hydrocarbon insecticide uptake by chemoorganotrophic bacteria has been investigated. Thirteen bacterial species were observed to sorb and concentrate (bioconcentratc)alpha-chlordane,beta chlordane, dieldrin, heptachlor epoxide, and lindane from aqueous systems. Bioconcentration, as expressed by the ratio of cellular insecticide in ng/mg (dry wt) to supernatant insecticide in ng/MUl, ranged from 10 for lindane byEnterobacter aerogenes to a high of 55,900 forbeta-chlordane byCaulobacter vibrioides var.limonus. Amounts of cellular chlorinated hydrocarbon insecticides (CHI) detected and the bioconcentration ratios were observed to have the following order in magnitude:alpha- orbeta-chlordane > dieldrin > heptachlor epoxide > lindane. This decreasing order was the inverse of reported water solubilities for the CHI and the inverse relationship was mathematically defined. The CHI were not easily removed from cells by washing (desorbing) and desorption was directly proportional to insecticide water solubility. Uptake of the CHI was rapid, near-maximum amounts being sorbed within 15 min, and pH 7 appeared optimal for bioconcentration as examined over the range pH 6 to 8. Implications of this investigation are that bioconcentration of CHI by bacteria might serve as a means of introducing these toxic compounds into aquatic food chains and that the bioconcentration phenomenon might lend itself as a treatment procedure for the intentional removal of residual CHI from water supplies and wastewater. PMID- 24241162 TI - A study of mixed continuous cultures of sulfate-reducing and methane-producing bacteria. AB - Ecological relationships between sulfate-reducing and methane-producing bacteria in mud of Lake Vechten have been studied by continuous culture studies using the chemostat technique. The maximum specific growth rate (MU max) and saturation constant (K s) were, respectively, 0.36 hr(-1) and 0.047 mM for lactate-limited growth ofDesulfovibrio desulfuricans and 0,011 hr(-1) and 0.17 mM for acetate limited growth ofMethanobacterium sp. Calculated values for the true molar growth yieldsY G) and maintenance coefficients (m) were 30.6 g bacterial mass/mole of lactate and 0.53 g substrate/g dry wt hr forD. desulfuricans and 37.8 g bacterial mass/mole of acetate and 0.54 g substrate/g dry wt hr forMethanobacterium.No growth ofMethanobacterium was observed at apS(2-) value (the hydrogen sulfide potential) of more than 11 and there was no effect on the growth atpS(2-) values above 13. In mixed continuous culture experiments the concentration of acetate decreased in the secondstage growth vessel, whereas that of methane increased stoichiometrically. If the substrate concentration in the reservoirs (S r) was increased from 0.1 to 0.5 mg/ml, the population ofDesulfovibrio increased and that ofMethanobacterium was washed out of the culture vessel, since the concentration of hydrogen sulfide reached apS(2-) value of 10.5. From the mixed continuous culture experiments a commensalism between the two species can be described, i.e., the acetate-fermentingMethanobacterium benefits from the acetate released byDesulfovibrio which is, in turn, not affected in the presence of the former. PMID- 24241163 TI - Microbial attachment to particles in marine and freshwater ecosystems. AB - Scanning electron microscopy observations ofin situ suspended marine and freshwater particles show diverse but similar modes of bacterial and fungal attachment. A survey of Sierra Nevada mountain lakes and pelagic and near-shore waters in the Pacific Ocean indicates that attachment is most noticeable in the near-surface waters where fresh dissolved and particulate input of carbon from phytoplankton and elevated temperatures favor microbial growth. The most common modes of attachment are: adhesive stalk formation, growth on adhesive webs, attachment by the use of pili-like appendages and slimy capsular secretions, and molecular or chemical sorption without the use of visualized structural appendages. Attached microbial growth is accelerated when particulate substrates are supplied, even when they are not rich in organic nutrients. This is the case in the Lake Tahoe basin, where microflora attached to eroded silts can significantly modify the organic carbon and nutrient content of such minerogenous particles. PMID- 24241164 TI - Observations of bacterial microcolonies on the surface of ferromanganese nodules from blake plateau by scanning electron microscopy. AB - Examination of the surface of freshly collected ferromanganese nodules by scanning electron microscopy revealed the presence of microcolonies of rod- and coccus-shaped bacteria which appeared to be anchored to the nodule surface by slime. The attachment of microcolonies by slime to the surface of freshly collected nodules argues against their being contaminants introduced during nodule collection or processing. These results corroborate cultural and biochemical detection of bacteria on ferromanganese nodules. PMID- 24241165 TI - Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK 506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population. AB - Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide DNA methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarrays and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently corroborated in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples, after adjusting for age and HPV status. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers. PMID- 24241167 TI - Spatial effect of new municipal solid waste landfill siting using different guidelines. AB - Proper implementation of landfill siting with the right regulations and constraints can prevent undesirable long-term effects. Different countries have respective guidelines on criteria for new landfill sites. In this article, we perform a comparative study of municipal solid waste landfill siting criteria stated in the policies and guidelines of eight different constitutional bodies from Malaysia, Australia, India, U.S.A., Europe, China and the Middle East, and the World Bank. Subsequently, a geographic information system (GIS) multi criteria evaluation model was applied to determine new suitable landfill sites using different criterion parameters using a constraint mapping technique and weighted linear combination. Application of Macro Modeler provided in the GIS IDRISI Andes software helps in building and executing multi-step models. In addition, the analytic hierarchy process technique was included to determine the criterion weight of the decision maker's preferences as part of the weighted linear combination procedure. The differences in spatial results of suitable sites obtained signifies that dissimilarity in guideline specifications and requirements will have an effect on the decision-making process. PMID- 24241166 TI - Genome-wide analysis of the bHLH transcription factor family in Chinese cabbage (Brassica rapa ssp. pekinensis). AB - Basic helix-loop-helix (bHLH) transcription factors are widely distributed in eukaryotic organisms and are thought to be one of the largest families of regulatory proteins. This important family of transcriptional regulators plays crucial roles in plant development. However, a systematic analysis of the bHLH transcription factor family has not been reported in Chinese cabbage. In this study, 230 bHLH transcription factors were identified from the whole Chinese cabbage genome and compared with proteins from other representative plants, fungi and metazoans. The Chinese cabbage bHLH (BrabHLH) gene family could be classified into 24 subfamilies. Phylogenetic analysis of BrabHLHs along with bHLHs from Arabidopsis and rice indicated 26 subfamilies. The identification, classification, phylogenetic reconstruction, conserved motifs, chromosome distribution, functional annotation, expression patterns and interaction networks of BrabHLHs were analyzed. Distribution mapping showed that BrabHLHs were non randomly located on the ten Chinese cabbage chromosomes. One hundred and twenty four orthologous bHLH genes were identified between Chinese cabbage and Arabidopsis, and the interaction networks of the orthologous genes were constructed in Chinese cabbage. Quantitative RT-PCR analysis showed that expressions of BrabHLH genes varied widely under different abiotic stress treatments for different times. Thus, this comprehensive analysis of BrabHLHs represents a rich resource, aiding the elucidation of the roles of bHLH family members in plant growth and development. Furthermore, the comparative genomics analysis deepened our understanding of the evolution of this gene family after a polyploidy event. PMID- 24241168 TI - Message from the Editor-in-Chief. PMID- 24241169 TI - Probing the surface of platinum nanoparticles with 13CO by solid-state NMR and IR spectroscopies. AB - The synthesis and full characterization of platinum nanoparticles (Pt NPs) prepared by decomposition of the Pt(dba)2 complex in the presence of CO and H2 and stabilized either sterically by a polymer, polyvinylpyrrolidone or chemically by a ligand, diphenylphosphinobutane, are reported. In these studies, (13)CO was used as a probe molecule to investigate the surface of the particles, using IR and solid-state NMR spectroscopies with magic angle spinning (MAS-NMR). Three nanosystems with different sizes are described: Pt/PVP/(13)CO (monomodal: 1.2 nm), Pt/dppb/(13)CO (bimodal: 1.2 nm and 2.0 nm) and Pt/dppb/H2 (monomodal: 2.0 nm) NPs. Spectroscopic data suggest a modification of the electronic state of the nanoparticles between 1.2 nm and 2.0 nm which can be related to the presence of Knight shift. PMID- 24241170 TI - Genetic modification of mesenchymal stem cells in spinal cord injury repair strategies. AB - Spinal cord injury (SCI) is a serious injury of the central nervous system and up until now there is no evident effective treatment for SCI. Axonal regeneration is the only way to restore functions after serious SCI that interrupt the long tracts mediating motor and sensory function. The hurdles for axonal regeneration in SCI include: glial scar tissue and molecular barriers, the inhibiting microenvironment, and the lack of sufficient neurotrophic support. Therefore, the key point of applying stem cells to treat SCI is to build a microenvironment conducive to the survival and differentiation of stem cells and regulate neurotrophic factor expression. Adult mesenchymal stem cells (MSCs) have been applied in experimental animal models and clinical trials of SCI. Genetic modification of MSCs can increase secretion of peptides or total length proteins with potential to repair SCI and promote survival of themselves and survival or regeneration of neurons. There are many proteins that have been applied to modified MSCs, such as neurotrophic factors (neurotrophin 3, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, nerve growth factor, and MNTS1), receptor tyrosine kinases (tropomyosin-related kinase C), and hepatocyte growth factor. In the future, there will be more molecules acting as transgenes in MSCs for treatment of SCI. PMID- 24241171 TI - Insights on the structural characteristics of Vim-TBS (58-81) peptide for future applications as a cell penetrating peptide. AB - The plasma membrane presents a remarkable barrier for the delivery of peptide and nucleic acid based drugs to the inside of cells. This restraint in the path of their development as therapeutic agents can be offset by their conjugation to cell penetrating peptides (CPPs) that can lead to an improved pharmacological profile. In this context, conformational behavior of Vimentin Tubulin Binding Site (TBS) peptide, Vim-TBS (58-81), was investigated for its acknowledged cell penetrating properties along with Trans-activating Tat (48-60) peptide and a pro apoptogenic peptide of p21/WAFI protein (p10). Also, the fusion peptides Vim- TBS (58-81)-p10 & Tat (48-60)-p10 were studied using molecular mechanics (MM) and molecular dynamics (MD) based strategies. MM results revealed formation of stable alpha-helix like secondary structures in Vim-TBS (58-81), Tat (48-60) and p10 peptides. In water, three peptides adopted either a helical structure or a random conformation; the stability of either of the two states being governed by the formation of polar contacts with the solvent. The fusion peptides formed helical structures after MD simulations but the structure obtained for the fusion peptide, Vim-TBS-p10 is relatively better characterized in terms of its amphipathic nature with a hydrophilic face formed by the positively charged residues facilitating a better interaction of this fusion peptide with the membrane as compared to that of Tat-p10 peptide. This is the first report on the conformational characteristics of the Vim-TBS (58-81) peptide and the fusion peptide, Vim-TBS (58-81)-p10. The results presented here are significant for their potential role in guiding and facilitating the future efforts of designing peptide based cell penetrating drugs. PMID- 24241172 TI - Characterization of anti-Tn-antigen MLS128 binding proteins involved in inhibiting the growth of human colorectal cancer cells. AB - MLS128 monoclonal antibody, which binds an epitope consisting of two or three consecutive Tn-antigens, inhibits colon cancer cell growth by binding to a 110 kDa glycoprotein (GP). Previous studies suggested a possible association of insulin-like growth factor-I receptor (IGF-IR) signaling in the inhibition of colon cancer cell growth by MLS128 (Morita et al. Biosci Trends. 3, 32-37, 2009; Zamri et al. ibid. 6, 303-312, 2012). The current study thus investigated the nature of 110 kDa GP and its possible association with IGF-IR. MLS128 treatment for 3 days caused down-regulation of IGF-IR and disappearance of 110 kDa GP in HT29 colon cancer cells. Immunoprecipitation/immunoblotting experiments did not reveal a direct association between the two molecules in HT29 cells. In LS180 and HT29 cells, however, 110 kDa GP and IGF-IR were found in microdomains. Treatment of these cells with MLS128 for 3 days caused a reduction in the IGF-IR and 110 kDa GP associated with microdomains. Two-dimensional gel electrophoresis/MLS128 immunoblotting of HT29 and LS180 cell lysates and immunoprecipitates revealed three spots, from which tryptic peptides were recovered for protein sequencing. Identification of 110 kDa GP was unsuccessful due to its heterogeneity and resistance to tryptic digestion. During this study, however, limited proteolysis of 110 kDa GP was observed in the microdomain-associated 110 kDa GP from HT29 and LS180 cells, suggesting that protease-susceptible sites or domains exist in the middle of 110 kDa GP. This information on limited proteolysis may provide a clue to identifying 110 kDa GP. PMID- 24241173 TI - A novel semi-synthetic andrographolide analogue A5 inhibits tumor angiogenesis via blocking the VEGFR2-p38/ERK1/2 signal pathway. AB - The present study is designed to observe the inhibitory effect of compound A5, a semi-synthetic analogue of the natural compound andrographolide, on angiogenesis and its underlying mechanism. Compound A5 is semi-synthesized from natural compound neoandrographolide. Andrographolide, the aglycon of neoandrograoholide, and A5 all inhibited vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs) proliferation, and that the inhibition shown by A5 is the best. A5 also inhibited VEGF-induced tube formation in HUVECs in a concentration-dependent manner. VEGF-induced neoangiogenesis in vivo was observed by Matrigel formation assay. The Matrigel picture and CD31 staining results showed that A5 inhibited VEGF-induced neoangiogenesis in vivo. Further, Western-blot results showed that A5 inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38 kinase. The antitumor effect of A5 was analyzed in a xenograft mouse tumor model inoculated with hepatoma Hep3B cells. The results showed that A5 decreased tumor weight and tumor size without affecting body weight in the xenograft mouse, and A5 also decreased CD31 staining in tumor tissue. Taken together, the present study demonstrates that compound A5 inhibits tumor growth via blocking neoangiogenesis, and the cellular VEGFR2-p38/ERK1/2 signal pathway. PMID- 24241174 TI - SL1122-37, a novel derivative of sorafenib, has greater effects than sorafenib on the inhibition of human hepatocellular carcinoma (HCC) growth and prevention of angiogenesis. AB - SL1122-37 is a novel derivative of sorafenib that was characterized by introducing trifluoromethyl on the 4-position of indazole. We aimed to evaluate the effects of SL1122- 37 on human hepatocellular carcinoma (HCC) growth and on umbilical vein vascular endothelial cells (HUVECs) angiogenesis. Its efficacy and mechanisms were compared with sorafenib. SL1122-37 significantly prevented PLC/PRF/5 cell proliferation as estimated by colorimetric assay. Flow cytometry analysis showed the induction of apoptosis and arrest of cell cycle in G1 phase. Western blotting showed the decrease of cyclin D1 and regulation of apoptotic proteins. Further analysis suggested that these effects of SL1122-37 might arise from its roles in the inhibition of multi-kinases, including c-Kit and its downstream targets and the Wnt/beta-catenin pathway in PLC/PRF/5 cells. SL1122-37 also possessed the activity of antiangiogenesis, showing the prevention of HUVEC migration and capillary tube formation. Western blotting indicated the inhibition of VEGF and phosphorylation of VEGFR-2 in HUVECs. Statistical analysis suggested that SL1122-37 might possess greater activities than sorafenib in the prevention of HCC proliferation and HUVEC angiogenesis. Conclusion, SL1122-37 could develop as a potent anticancer agent for the treatment of HCC. PMID- 24241175 TI - Japan's advanced medicine. AB - Like health care systems in other developed countries, Japan's health care system faces significant challenges due to aging of the population and economic stagnation. Advanced medicine (Senshin Iryou) is a unique system of medical care in Japan offering highly technology-driven medical care that is not covered by public health insurance. Advanced medicine has recently developed and expanded as part of health care reform. Will it work? To answer this question, we briefly trace the historical development of advanced medicine and describe the characteristics and current state of advanced medical care in Japan. We then offer our opinions on the future of advanced medicine with careful consideration of its pros and cons. We believe that developing advanced medicine is an attempt to bring health care reform in line rather than the goal of health care reform. PMID- 24241176 TI - Standardizing management of hepatocellular carcinoma in China: devising evidence based clinical practice guidelines. AB - Evidence-based clinical practice guidelines (CPGs) have been used in many countries around the world to promote standardized management of hepatocellular carcinoma (HCC). Guidelines implemented in Japan provide a good example of "translating the best current research evidence into clinical practice and obtaining new evidence in the course of influencing practitioners' attitudes and clinical decision-making". The Japanese guidelines have achieved remarkable results in terms of HCC management in Japan. The first Japanese evidence-based CPGs for HCC (J-HCC Guidelines) were published in 2005 and then revised in 2009. A second updated version that incorporates new evidence was just published on October 15, 2013. China accounts for 55% of HCC cases worldwide. Although the Government devised a series of directives on the management of HCC and Chinese Guidelines on HCC were published in 2009, neither were based on systematic review and evaluation of the literature and neither included recommendations supported by data. The novel concept of "precision surgery" was recently proposed in China. This concept is based on surgeons' clinical experience and should encourage the standardized management of HCC in China. However, recommendations supported by data are still urgently needed to guide clinical decision-making in order to facilitate standardized management of HCC in China. PMID- 24241177 TI - Complementary and alternative medicine is expected to make greater contribution in controlling the prevalence of influenza. AB - Influenza pandemics are a serious threat to public health in today's world. In the past 10 years, the outbreak of three forms of severe influenza--H5N1, H1N1, and H7N9--has caused tremendous loss of life and property. In order to better cope with pandemics, antivirals such as oseltamivir are being stockpiled in great quantities, placing a substantial burden on government budgets and potentially resulting in massive waste because of the uncertainty as to when an influenza pandemic will strike and whether emerging virus strains will be resistant to the stockpiled drugs. Complementary and alternative medicine (CAM) is generally available, affordable, and commonly used in China and many other countries and CAM has a long track record of fighting influenza. The Chinese Government appropriated funds to intensively investigate herbal medicines in accordance with the principles of evidence-based medicine in order to identify effective, inexpensive, and easily stockpiled medicines. Thus far, several drugs including Shufeng Jiedu capsules, Lianhua Qingwen capsules, Maxing Shigan decoction, Yinqiao powder, and Jinhua Qinggan granules have demonstrated effectiveness in fighting influenza. In the future, CAM is expected to make greater contribution in controlling the prevalence of influenza pandemics. PMID- 24241178 TI - Combat with emerging infectious diseases: clinicians should do better. AB - In the spring of 2013, an emerging infectious disease emerged in China, 132 cases of human were infected with the H7N9 avian influenza virus, 39 cases were resulted in death within 3 month, which sparked a global concern about public health. Many reports have been published about this disease, including clinical characteristics and genomic information. However, more emerging infectious disease may infect human in the future. Confronted with the escalating scale of compounding probabilities, physicians or clinicians as the first line that meet patients who suffering from emerging infectious disease, we should do better by using our intellect and strong will to carry out public health measures, biomedical research, and technological advances. PMID- 24241180 TI - A density functional theory study on oxygen reduction reaction on nitrogen-doped graphene. AB - Nitrogen (N)-doped carbons reportedly exhibit good electrocatalytic activity for the oxygen reduction reaction (ORR) of fuel cells. This work provides theoretical insights into the ORR mechanism of N-doped graphene by using density functional theory calculations. All possible reaction pathways were investigated, and the transition state of each elementary step was identified. The results showed that OOH reduction was easier than O-OH breaking. OOH reduction followed a direct Eley Rideal mechanism (the OOH species was in gas phase, but H was chemisorbed on the surface) with a significantly low reaction barrier of 0.09 eV. Pathways for both four-electron and two-electron reductions were possible. The rate-determining step of the two-electron pathway was the reduction of O2 (formation of OOH), whereas that of the four-electron pathway was the reduction of OH into H2O. After comparing the barriers of the rate-determining steps of the two pathways, we found that the two-electron pathway was more energetically favored than the four electron pathway. PMID- 24241179 TI - Modified nucleotides m(2)G966/m(5)C967 of Escherichia coli 16S rRNA are required for attenuation of tryptophan operon. AB - Ribosomes contain a number of modifications in rRNA, the function of which is unclear. Here we show--using proteomic analysis and dual fluorescence reporter in vivo assays--that m(2)G966 and m(5)C967 in 16S rRNA of Escherichia coli ribosomes are necessary for correct attenuation of tryptophan (trp) operon. Expression of trp operon is upregulated in the strain where RsmD and RsmB methyltransferases were deleted, which results in the lack of m(2)G966 and m(5)C967 modifications. The upregulation requires the trpL attenuator, but is independent of the promotor of trp operon, ribosome binding site of the trpE gene, which follows trp attenuator and even Trp codons in the trpL sequence. Suboptimal translation initiation efficiency in the rsmB/rsmD knockout strain is likely to cause a delay in translation relative to transcription which causes misregulation of attenuation control of trp operon. PMID- 24241181 TI - Some insights into the binding mechanism of the GABAA receptor: a combined docking and MM-GBSA study. AB - Gamma-aminobutyric type A receptor (GABAAR) is a member of the Cys-loop family of pentameric ligand gated ion channels (pLGICs). It has been identified as a key target for many clinical drugs. In the present study, we construct the structure of human 2alpha12beta2gamma2 GABA(A)R using a homology modeling method. The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1) were identified in the binding site. To gain insight into the binding affinity, molecular dynamics (MD) simulations were performed for all the receptor-ligand complexes. We also examined single mutant GABA(A)R (His102A) in complexes with the three drugs (flurazepam, eszopiclone and zolpidem) to elucidate receptor-ligand interactions. For each receptor-ligand complex (with flurazepam, eszopiclone and zolpidem), we calculated the average distance between the C(alpha) of the mutant residue His102A (alpha1) to the center of mass of the ligands. The results reveal that the distance between the C(alpha) of the mutant residue His102A (alpha1) to the center of flurazepam is larger than that between His102 (alpha1) to flurazepam in the WT type complex. Molecular mechanic-generalized Born surface area (MM-GBSA)-based binding free energy calculations were performed. The binding free energy was decomposed into ligand-residue pairs to create a ligand-residue interaction spectrum. The predicted binding free energies correlated well (R(2) = 0.87) with the experimental binding free energies. Overall, the major interaction comes from a few groups around His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1). These groups of interaction consist of at least of 12 residues in total with a binding energy of more than 1 kcal mol(-1). The simulation study disclosed herein provides a meaningful insight into GABA(A)R-ligand interactions and helps to arrive at a binding mode hypothesis with implications for drug design. PMID- 24241182 TI - A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis. AB - In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate. PMID- 24241183 TI - Cytoplasmic male sterility and nuclear restorer genes in a natural population of Beta maritima: genetical and molecular aspects. AB - One natural population (F0 generation) of Beta maritima situated on the French Atlantic coast has been analysed. It was composed of 62% female, 30% hermaphrodite and 8% intermediate plants. The analysis of half-sib progeny (F1 generation) obtained from in situ open pollination demonstrates the cytoplasmic determination of male sterility in Beta maritima and the restoration of fertility by nuclear genes. The mitochondrial DNA (mtDNA) and the chloroplast DNA (ctDNA) of sixteen F1 plants, extracted from offspring of the three sexual phenotypes, were analysed using the restriction enzymes Sal I and Bam HI, respectively. Two cytoplasmic lines with their own peculiar genetic characteristics were distinguished using the restriction enzyme patterns of mtDNA: (i) the S cytoplasmic line was found in segregating progeny of two F0 plants; all three phenotypes were produced (that is, progeny including hermaphrodite, female and intermediate plants); (ii) the N cytoplasmic line was found in the progeny of one F0 hermaphrodite plant; this produced only hermaphrodites. Thus, segregating and non-segregating hermaphrodite F0 plants can be distinguished. The nuclear genes maintaining sterility or restoring fertility are expressed in line S. At the same time the analysis of Beta vulgaris material has been carried out at the molecular level: N cytoplasmic lines of B. vulgaris and B. maritima differed only by 3 fragments of mtDNA; but the S cytoplasmic line of B. maritima was very different from Owen's cytoplasmic male sterile line of B. vulgaris. No variation in the ctDNA pattern was detected within and between the two taxa. PMID- 24241184 TI - Computerized analysis of chromosomal parameters in karyotype studies. AB - A study is presented of the possibilities and limitations of semi-automated karyotype analysis on the basis of chromosome length and centromere index. A number of computer programs have been developed for 1) quick and precise measurements of chromosome arm length with the help of a graphics tablet, 2) computing (relative) length and centromere index and statistical analyses of the data, and 3) representation of these chromosomal parameters in two-dimensional scattergrams. An ellipse representing 95% of the probability mass is drawn around the bivariate mean of each chromosome. The size and orientation of the axes are calculated from repeated measurements of the chromosomes of one metaphase plate. If there is a correlation between length and centromere index, which is often the case, the axes of the ellipse are tilted. Incorporation of such a covariance analysis proved to be of great importance for an accurate karyotype analysis. The "Computer Aided Karyotyping" package does not contain routines for an automated classification of the chromosomes. The main reason is that the variation in length and centromere index of a given chromosome in different cells is often much larger than the variation between nonhomologous chromosomes. In addition, it was our aim to develop universal karyotyping aids which can be used regardless of the species studied. PMID- 24241185 TI - Cytogenetic analysis of structural rearrangements in three varieties of common wheat, Triticum aestivum. AB - The winter wheat varieties 'Starke' and 'Cappelle Desprez' and the spring wheat 'Chinese Spring' were analysed for structural chromosome rearrangements that resulted in the formation of multivalents in F1 hybrids. The analyses were carried out using hybrids involving euploids, monosomic and ditelosomic stocks, and double-monotelodisomic constructs. The study confirmed that 'Cappelle Desprez' differs from 'Chinese Spring' in a reciprocal translocation between chromosomes 5B and 7B (Riley et al. 1967); a translocation involving chromosomes 3B and 3D could not be verified. Furthermore, the analysis showed that 'Starke' differs from 'Chinese Spring' in a reciprocal translocation between chromosomes 7A and 7D. Both translocations have a coefficient of multivalent realisation of about 0.84. Further multivalents in euploid 'Starke', in euploid and some aneuploid stocks of 'Cappelle Desprez', and in euploid as well as various types of aneuploid hybrids between all three varieties could nearly all be explained hypothesizing that chromosome 2B of both 'Starke' and 'Cappelle Desprez' is a duplication-deficiency chromosome. In the hypothesis a part of the long arm of 2B is missing and replaced by a duplicated part of the long arm of chromosome 2D. The multivalents of this rearrangement showed an average coefficient of realisation of about 0.09. PMID- 24241186 TI - Mitochondrial DNA duplication/deletion events and polymorphism of the C group of male sterile maize cytoplasms. AB - Five accessions of members of the C group of male sterile maize cytoplasms (BB, C, ES, PR, and RB) in two nuclear backgrounds (A619 and A632) were examined to elucidate the nature of mitochondrial genome diversity within a related group of cytoplasms. Cosmid and plasmid clones carrying single copy and recombinationally active sequences from N and S cytoplasms of maize were used as probes. Although restriction patterns are quite similar, each of the five could be discriminated by evidence of sequence duplication and recombination, deletion of recombinationally active sequences of N, normal cytoplasm, population of mini circular DNAs, and by restriction patterns. Each member of the group carried a 1,913 bp minicircular mtDNA, while all entries but RB carried a 1,445 bp minicircular mtDNA. Members of the C group clearly are not molecularly identical; evolution of the group included principal genome reorganization involving sequence duplication/deletion events, apparently independent of the cms trait. PMID- 24241187 TI - Associations among inbred lines of maize using electrophoretic, chromatographic, and pedigree data : 1. Multivariate and cluster analysis of data from 'Lancaster Sure Crop' derived lines. AB - Associations among 18 'Lancaster Sure Crop' derived inbred lines of maize (Zea mays L.) were determined using multivariate and cluster analysis. Objectives were to assess the degree of unique characterization among lines afforded by reversed phase high-performance liquid chromatography (RP-HPLC) and starch gel electrophoresis of allozymes and to compare associations among lines revealed by biochemical and pedigree data. RP-HPLC revealed 11 different chromatograms that uniquely identified 79% of lines that differed by more than isogenic or near isogenic segments. Allozymic data for 21 loci provided unique discrimination among 93% of non-isogenic lines. Chromatographic and allozymic data together provided unique characterization of all non-isogenic lines. Cluster and multivariate analyses of biochemical data associated lines into three groups that would have been expected on the basis of pedigree breeding records. More detailed associations were dependent upon the data set employed. Multivariate and cluster analysis of chromatographic, electrophoretic, and pedigree data could be useful in revealing more detailed associations among elite germplasm than hitherto available, thus providing data pertinent to line and hybrid development, plant variety protection, and germplasm security. PMID- 24241188 TI - Bypassing prefertilization barriers to hybridization in Nicotiana using in vitro pollination and fertilization. AB - In vitro pollination of placenta attached ovules was useful in bypassing unilateral incongruity barriers for several Nicotiana interspecific hybrid combinations (N. tabacum cv. 'Ky 17' X N. amplexicaulis, 'Ky 17' X N. benthamiana, and 'Ky 17' X N. repanda). By measuring the pollen tube growth over time, prefertilization barriers were determined to be the cause of the incongruity. Seedling necrosis was a problem in the development of the N. amplexicaulis hybrid and it prevented maturation of the N. repanda hybrid. Callus produced from cotyledons of the N. amplexicaulis hybrid eventually resulted in plants that survived to maturity. This procedure was not successful for the N. repanda materials. The N. amplexicaulis and N. benthamiana hybrids were sterile but following chromosome doubling by midrib culture, male and female fertile plants were produced.Conventional hybridization, fertilized ovule culture, and in vitro pollination were unsuccessful in obtaining hybrids of 'Ky 17' crossed with N. arentsii or N. bonariensis. Apparently, strong postfertilization barriers prevent the production of viable seed of these hybrids. Each of the N. repanda - N. tabacum reciprocal hybrids could not be rescued using callus culture; this adds support to the existence of strong sexual postfertilization barriers. A recent report, however, showed that it was possible to obtain this hybrid using the technique of somatic hybridization. Thus, it appears that it may also be possible to obtain asexual hybrids of N. arentsii and N. bonariensis with N. tabacum. PMID- 24241189 TI - Modified full-sib selection and estimation of genetic parameters. AB - A cycle of full-sib selection is completed in three seasons while that of a modified method is completed in two seasons. In modified full-sib selection, selected families can be recombined and new families generated following a partial-diallel cross. The components of genetic variance can be estimated from the partial-diallel analysis of such families. Thus, in addition to performing selection, genetic parameters can be estimated. PMID- 24241190 TI - Isozymic variability of traditional rice (Oryza sativa L.) in Africa. AB - Eight hundred and thirtyone traditional varieties of rice, Oryza sativa L., were collected in Africa and analysed for their isozymic variability on 15 enzymatic systems, representing 37 presumed loci. There appears to be a correlation between the type of rice growing and the two groups Indica and Japonica. The degree of genetic diversity is nearly equal in African rice and the Asian one. Alleles due to introgression or mutational events were identified. The results suggest that the evolution of O. sativa is continuous in Africa by means of inter-subspecific or inter-specific crosses. PMID- 24241191 TI - Genetics of rye phosphatases: evidence of a duplication. AB - Genetic analyses were conducted on alkaline phosphatases of the endosperm of dry kernels and leaf acid phosphatases in four open pollinated and one inbred line of cultivated rye (Secale cereale L.). A total of seven alkaline phosphatase isozymes were observed occurring at variable frequencies in the different cultivars analyzed. We propose that at least five loci control the alkaline phosphatases of rye endosperm - Alph-1, Alph-2, Alph-3, Alph-4 and Alph-5 - all of which have monomeric behaviour. The leaf acid phosphatases are controlled by one locus and have a dimeric quaternary structure. All loci coding for alkaline phosphatase isozymes showed one active, dominant allele and one null, recessive allele, except for the locus Alph-3 which showed two active, dominant alleles and one null, recessive one. The linkage analyses suggest the existence of two linkage groups for alkaline phosphatases: one of them would contain Alph-2, Alph 4, Alph-5 and the locus/loci coding isozymes 6 and 7. This linkage group is located in the 7RS chromosome arm. The other group would include Alph-1 and Alph 3 loci, being located in the 1RL chromosome arm. Leaf acid phosphatases have been previously located in the 7RL chromosome arm. Our data also support an independent relationship between loci controlling the endosperm alkaline phosphatases and leaf acid phosphatases. PMID- 24241192 TI - Chromosomal location of structural genes controlling isozymes in Hordeum chilense : 3. Esterases, glutamate oxaloacetate transaminase and phosphoglucomutase. AB - Polyacrylamide and starch gel electrophoresis of esterase (EST), glutamate oxaloacetate transaminase (GOT) and phosphoglucomutase (PGM) isozymes in Hordeum chilense, Triticum turgidum conv. durum, the amphiploid H. chilense X T. turgidum (Tritordeum), and the durum wheat/H. chilense monosomic addition lines revealed the chromosomal location of one EST locus, two GOT loci and one PGM locus. Loci Est-H (ch)1 and Got-H (ch)2 were found on chromosome 6H(ch),Got-H (ch)3 on chromosome 3H(ch), and Pgm-H (ch)1 on chromosome 4H(ch). These results lend evidence for the assumed homoeology relationships between chromosomes of Triticeae species. PMID- 24241193 TI - Genetic and biochemical basis of scent in rice (Oryza sativa L.). AB - The inheritance and biochemical basis of scent in rice was studied in the F2 population along with the F1 and its two parents, scented and non-scented 'Pokura' rice strains. The F1 plants were found to be nonscented while the F2 plants seggregated into a 3?1 ratio (non-scented: scented). In scented F2 seggregants and in the scented parental strain, a fast moving esterase isozyme, Rf 0.9, is missing whereas it is present in all nonscented F2 seggregants, F1s, and in the non-scented parent. This suggests that the absence of a specific esterase isozyme is associated with the scent character in rice. PMID- 24241194 TI - The peroxidase isozymes of the wheat kernel: tissue and substrate specificity and their chromosomal location. AB - Peroxidase isozymes were studied in the Triticum aestivum L. kernel and in nullisomic-tetrasomic and ditelocentric combinations of 'Chinese Spring' wheat. Analyses were carried out on different parts of dry kernels (embryo plus scutellum and endosperm) using polyacrylamide and starch gel electrophoresis, different electrophoretic buffer systems and various staining methods. The peroxidase isozymes showed a low substrate-specificity and a high tissue specificity. The embryo plus scutellum and the endosperm always presented different peroxidase patterns. Endosperm peroxidases were associated with chromosome arms 7DS, 4BL and 7AS; whereas the embryo plus scutellum isozymes were related to chromosome arms 3AL, 3BL and 3DS. The different results obtained using various electrophoretic techniques are due to the buffer system used. All staining procedures employed revealed the same peroxidase isozymes. PMID- 24241195 TI - Sources and inheritance of resistance to leaf curl virus in Lycopersicon. AB - One hundred and twenty-two varieties, lines and wild accessions of Lycopersicon were screened under three different regimes during the autumn/winter season of 1982-83 and 1983-84 for resistance to tomato leaf curl virus (TLCV). L. hirsutum f. glabratum ('B6013') and L. hirsutum f. typicum ('A1904') proved to be highly resistant to TLCV in all three environments. Various accessions of L. peruvianum were also highly resistant. L. pimpinellifolium ('A1921') exhibited no TLCV symptoms within 90 days. Of the cultivated varieties, 'Acc 99' exhibited the minimim score for susceptibility; 'AC 142', 'Collection No. 2', 'Kalyanpur Angurlata' and 'HS 101' had a low rating for virus incidence. The inheritance of resistance was studied in the interspecific crosses between a TLCV resistant line of L. pimpinellifolium ('A1921') and five ('HS 101', 'HS 102', 'HS 110', 'Pusa Ruby' and 'Punjab Chhuhara') susceptible cultivars of L. esculentum. Parents, F1, F2 and backcross progenies were artificially inoculated with local strains of TLCV using vector the viruliferious whitefly, Bemisia tabaci (Genn.). Data indicated that the resistance of L. pimpinellifolium ('A 1921') is monogenic and incompletely dominant over susceptibility. PMID- 24241196 TI - Genetics of resistance to red pumpkin beetle (A ulacophora foveicollis) in summer squash (Cucurbita pepo L.). AB - Resistance to red pumpkin beetle in summer squash was found to be controlled by polygenes. Diallel and Triple test cross analysis revealed the preponderance of non-additive and additive gene effects for resistance respectively. Absence of epistasis for resistance was indicated by both tests. PMID- 24241197 TI - Influence of Zinnia angustifolia HBK genotype on embryonic and vegetative development of Z. angustifolia x Z. elegans Jacq. interspecific hybrids. AB - Interspecific crosses between Zinnia angustifolia clones (maternal parents) and Z. elegans lines (paternal parents) were performed to investigate postzygotic barriers among Z. angustifolia X Z. elegans hybrids and to determine influence of parental genotype on embryonic and vegetative development of interspecific hybrids. Variation in percentage of emerged seedlings (PES) and percentage of morphologically normal hybrids (PNH) was attributable to Z. angustifolia clones with minor or no effect attributable to Z. elegans lines. Heterogeneity in PES values among Z. angustifolia clones was due to differences in amount of hybrid embryo breakdown and ungerminable seed. Cytological observations of normal and abnormal interspecific hybrids revealed similar chromosome numbers (2n=23) but indicated a low mitotic index for abnormal hybrids. Genetic analysis of PES and PNH suggested control by multiple genes inherited from the Z. angustifolia genome. Adequate sampling of the Z. angustifolia gene pool would permit exploitation of genetic variability present within the species and allow improvements in PES and PNH for interspecific hybrids. PMID- 24241198 TI - A method for the estimation of gene flow parameters from a population structure caused by restricted gene flow and genetic drift. AB - A method has been developed which enables the estimation of the plant gene flow parameters sigmap (pollen dispersal), sigmas (seed dispersal) and t (outcrossing rate) from a selection-free continuously structured population in equilibrium. The method uses Wright's F-coefficients and introduces a new F-function which describes the genetic similarity as a function of the spatial distance. The method has been elaborated for wind pollinated plant species but can be modified for insect pollination and for animal species. In practice allozymes will provide for the necessary neutral genetic variation. The more loci used and the more intermediate the gene frequencies, the more reliable the results. For the estimation of sigmap and t together (when the outcrossing rate is not known) at least two chromosomally unlinked loci are required. The method for estimating sigmas depends on whether the plant species is annual or perennial. The mechanism of selfing has been analysed by the explanation of the value of t by three components: population density (d), pollen flow (sigmap) and relative fertilization potential of own pollen (Z). The concepts of neighbourhood size and isolation by distance, developed by Wright, who used a single gene flow parameter sigma, have been extended to the situation which is realistic for seed plants, using all three parameters sigmap, sigmas and t. When sigmap is large with respect to sigmas, sigmas largely determines the value of the neighbourhood size, whereas sigmap is the most dominating factor in isolation by distance. The use of "local effective population size" and "mean gene transport per generation" instead of "neighbourhood size" and "neighbourhood area", respectively, is proposed to avoid confusion. Computer simulations have been carried out to check the validity and the reliability of the method. Populations of 200 plants, using two or three loci with intermediate allele frequencies, gave good results in the calculation of sigmap with known value of t and of sigmas and Ne. With unknown t, especially with lower values of t, larger populations of at least 1,000 plants are necessary to obtain reasonably accurate results for sigmap and mean gene transport per generation M. PMID- 24241199 TI - Genotypic stability analysis of yield and related agronomic characters in wheat Agropyron derivatives under varying watering regimes. AB - Genotypic stability of grain yield and yield related traits was estimated for the 8 wheat-Agropyron derivatives, 441, 442, 'Vostock', 'PPG 56', 'PPG 56SS', 449, 450 and 441SS, together with two spring wheat controls, 'Drabant' and 'Sv 01382', grown under varying watering regimes for two years. Differences among environments, genotypes and their interactions were highly significant for all traits. The genotypes X environments linear response were significant for number of spikelets per main spike, grain number per main spike and single grain weight. No significant linear responses were detected for grain yield or the rest of yield related traits. Deviations from linear responses were highly significant for all traits under study. Grain yield stability was not associated with the stability of yield components. 'PPG 56SS' was identified as the stable variety with the highest mean grain yield per plant under the severe stress environment. Mean grain yields in the severe stress environment were correlated with the genotypic stability parameter "alpha". The severe stress environment was recognized as the optimum test environment. The study revealed a shift in the association between grain yield per plant and its components under the varying environments. PMID- 24241200 TI - Genetic transformation in two potato cultivars with T-DNA from disarmed Agrobacterium. AB - Derivatives of potato (Solanum tuberosum cv.'s 'Maris Bard' and 'Desiree') transformed with disarmed T-DNA from genetically engineered Agrobacterium tumefaciens strains were isolated. The transformed plants were recovered from shoot-forming tumours induced by infection of wounds with mixedcultures of shoot inducing A. tumefaciens strains T37 and either Agrobacterium strain LBA1834(pRAL1834), (Hille et al. 1983) or LBA4404(pBIN6; pRAL4404), (Bevan 1984). Two small-scale feasibility experiments gave at least four 'Maris Bard' plants transformed with pRAL1834 T-DNA and two 'Desiree' plants with pBIN6 T-DNA. The transformed 'Maris Bard' plants were morphologically abnormal and highly aneuploid. This was probably an unfortunate side-effect of a tissue culture-step introduced to promote the efficiency of shoot regeneration. The transformed 'Desiree' plants, in contrast, were isolated without promoting additional shoot growth. They were morphologically normal, contained 47 and the euploid 48 chromosomes per cell respectively and had improved growth on media containing kanamycin. PMID- 24241201 TI - Production of potato monohaploids (2n=x=12) through prickle pollination. AB - Data are presented on the potential of gynogenesis for the production of monohaploids and on factors affecting their frequency and relative vigour. Diploid Solanum tuberosum L. and S. tuberosumxS. phureja Juz et Buk hybrids were used as maternal parents and selected S. phureja clones as prickle pollinators with embryo-spot and nodal band as dominant seed and plant marker. About 2 million seeds were screened for absence of embryo-spot. After raising plants from phenotypically spotless seeds, further screening for absence of nodal bands and for ploidy level was carried out. Finally more than 500 monohaploid plants from three genetically different groups of maternal parents were obtained. Frequency and vigour of the monohaploids were clearly dependent on their maternal genotypes. The data also indicated an effect of the pollinator genotype, the physiological stage of the maternal plant and the environment on monohaploid frequency. On the basis of these results the possibility of breeding for a higher monohaploid production rate and for more stable and vigorous monohaploids is discussed. Furthermore, gynogenesis and androgenesis are compared. It is suggested that both should be used in order to obtain monohaploids from sufficiently various diploid breeding material. PMID- 24241202 TI - Confidence interval estimators for heritability for several mating and experiment designs. AB - Confidence interval estimators have not been described for several heritability (H) estimators relevant to recurrent family selection. Previously described H interval estimators do not apply to onefactor mating designs in split-plot in time experiment designs in one or more locations, one-factor mating designs for several experiment designs in two or more locations and years, and two-factor mating designs for several experiment designs in two or more locations or years. Our objective was to derive H interval estimators for these cases. H reduced to a function of constants and a single expected mean square ratio in every case; H=1 E(M')/E(M") where E(M') is a linear function of expected mean squares and E(M") is a single expected mean square. It was shown that F'=[M"/E(M")]/[M'/E(M')] has an approximate F-distribution with df" and df' degrees of freedom, respectively, where M' and M" are mean squares corresponding to E(M') and E(M"), respectively. H is a function of F', therefore, we used F' to define an approximate (1-alpha) interval estimator for H. PMID- 24241203 TI - Problems of interpreting results obtained in studies of somaclonal variation in gliadin proteins in wheat. AB - It is quite likely that somacloning increases the frequency of mutations: this has, in fact, been claimed for gliadin proteins. However, in such instances it is important to distinguish between true mutations and presumed changes in regenerants due to cross pollination or admixture. We present herein arguments that some so-claimed somaclonal variants in gliadincoding genes are unlikely to be due to mutations since they would have had to involve directed changes at several loci simultaneously. PMID- 24241204 TI - NuMA phosphorylation dictates dynein-dependent spindle positioning. PMID- 24241205 TI - Immunovirotherapy for glioblastoma. PMID- 24241206 TI - WNKs in Wnt/beta-catenin signaling. PMID- 24241207 TI - Molecular targeting of mutagenic AID and APOBEC deaminases. PMID- 24241208 TI - Biogenesis and folding of beta-barrel membrane proteins. PMID- 24241209 TI - Rearranging the chromatin for pluripotency. PMID- 24241211 TI - Antitumor effects of BI-D1870 on human oral squamous cell carcinoma. AB - PURPOSE: Among the signaling pathways implicated in the tumorigenesis of oral squamous cell carcinoma (OSCC) is the extracellular signal-regulated kinase mitogen-activated protein kinase pathway, a downstream target of which is a family of serine/threonine kinases known as the 90 kDa ribosomal S6 kinases (RSKs). This study aims to investigate the role of BI-D1870, a specific inhibitor of p90 RSKs, in a panel of OSCC cell lines. METHODS: The antitumor effects and mechanisms of BI-D1870 were assessed by MTT assays, flow cytometry, Western blotting, transfection, and confocal microscopy. RESULTS: BI-D1870 exhibited a dose-responsive antiproliferative effect on OSCC cells with relative sparing of normal human oral keratinocytes. The compound inhibited the downstream RSK target YB-1 and caused apoptosis as evidenced by PARP cleavage, activation of the caspase cascade, and the presence of pyknotic nuclei in the 4,6-diamidino-2 phenylindole assay. In addition, BI-D1870 also induced G2/M arrest by modulating the expression of p21 and other cell cycle regulators. Other newly discovered anticancer attributes of BI-D1870 included the generation of reactive oxygen species and increases in endoplasmic reticulum stress and autophagy. CONCLUSIONS: Together, these results suggest the translational value of BI-D1870 in oral squamous cell carcinoma therapy. PMID- 24241210 TI - A phase I trial of flavopiridol in relapsed multiple myeloma. AB - PURPOSE: Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. METHODS: Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus and then continuous infusion weekly for 4 weeks in a 6-week cycle. RESULTS: Fifteen patients were treated at three dose levels (30 mg/m(2) bolus, 30 mg/m(2) CIV to 50 mg/m(2) bolus, and 50 mg/m(2) CIV). Cytopenias were significant, and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients and grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein >50 % that did not persist. PK properties were similar to prior publications, and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. CONCLUSIONS: Flavopiridol as a single agent given by bolus and then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723). PMID- 24241212 TI - Results of a phase I, open-label, randomized, crossover study evaluating the effects of linifanib on QTc intervals in patients with solid tumors. AB - PURPOSE: Linifanib is a selective inhibitor of the vascular endothelial growth factor and platelet-derived growth factor family of tyrosine kinase inhibitors. The purpose of this high-precision QT study was to evaluate the effects of linifanib on cardiac repolarization in patients with advanced metastatic tumors. METHODS: Enrolled patients (n = 24) had measurable disease refractory to standard therapies, ECOG performance status of 0-1, and adequate organ function. Patients were randomized in a 2-sequence, 2-period crossover design. Serial ECG measurements and pharmacokinetic samples were collected for each crossover period. An intersection-union test was performed for time-matched baseline adjusted QTcF intervals. An exposure-response analysis was explored to correlate the plasma concentration and QTcF. RESULTS: The maximum 95 % upper confidence bound for the baseline-adjusted QTcF was 4.3 ms at hour 3 at the maximum tolerated linifanib dose of 0.25 mg/kg. Linifanib did not meet the regulatory threshold (10 ms) for QT prolongation. Exposure-response modeling showed that the QTcF change was not significant at the maximum plasma concentration. CONCLUSIONS: Linifanib does not significantly affect cardiac repolarization in patients with advanced solid tumors. PMID- 24241213 TI - Application of dairy proteins as technological and nutritional improvers of calcium-supplemented gluten-free bread. AB - Effect of dairy proteins on gluten-free dough behavior, and nutritional and technological properties of gluten-free bread was evaluated. Experimental doughs, containing dairy powders, showed low consistency. Obtained gluten-free breads were rich in proteins, and, regarding the energy value delivered by proteins, they could be considered as a source of proteins or high in proteins. Applied dairy proteins affected the technological properties of experimental breads causing a significant (p < 0.05) increase of the specific volume, crust darkening, and crumb lightness, depending on the dairy supplementation level, rather than the protein type. Dairy proteins incorporated at a 12% level, significantly (p < 0.05) decreased the hardness; nevertheless, the highest amount of proteins tested led to the opposite effect. These results indicate that milk proteins tested could be successfully added to gluten-free bread with beneficial effects on technological and nutritional properties. PMID- 24241214 TI - Porous tantalum shells and augments for acetabular cup revisions. AB - PURPOSE: The purpose of this study was to evaluate early functional results of revision hip arthroplasty with pelvic bone loss revised with porous tantalum (PT) acetabular components. METHODS: Twenty-five consecutive patients (25 hips) with loose acetabular components after total hip arthroplasty with a minimum of Paprosky IIa pelvic bone loss treated with PT cups with and without modular augments were retrospectively reviewed. Clinical outcomes were assessed using Harris hip score, and Western Ontario and McMaster Universities scores. Mean follow-up was 20.5 months and no patient was lost during follow-up. RESULTS: The average Harris hip score, and Western Ontario and McMaster Universities scores improved from 40 and 36 preoperatively to 79 and 73 postoperatively, respectively. No statistically significant differences in functional outcome scores were found between the group with moderate (Paprosky IIa, b) and severe (Paprosky IIc or more) acetabular bone loss. At the most recent radiographic evaluation, 24 cups demonstrated no lucent lines and 1 cup had lucent lines but remained well fixed. One cup was revised for traumatic dislocation but was found well fixed at open reduction. There were no septic or aseptic failures in this series. CONCLUSION: While awaiting longer-term follow-up studies, trabecular metal components show sufficient primary stability and appear suitable for revision hip arthroplasty with acetabular bone loss. PMID- 24241215 TI - Posterior percutaneous plating of the humerus. AB - OBJECTIVE: This is a prospective case series study, which was designed to evaluate the clinical outcome of posterior percutaneous plating of the humerus. MATERIALS AND METHODS: From the year 2010 to 2011, 37 patients with middle and distal third humeral fractures who met the inclusion criteria were surgically treated by minimally invasive plate osteosynthesis through posterior approach. Their age ranged from 19 to 43 with an average of 27.8 years. Type of fractures varied from B to C, and all of them were traumatic. RESULTS: Patients were followed up for a period varied from 12 to 24 months with an average of 18. There were no cases of intraoperative complications, infection or metal failure. Union was achieved in all of them within 16-21 weeks with an average of 18. Iatrogenic postoperative temporary neuropraxia of the radial nerve palsy was observed in two patients. All patients achieved normal range of shoulder and elbow motion within 3 months after surgery. The average Quick DASH score at 12-month follow-up was 30. According to patient's satisfaction, all of them returned to the usual pre injury activity level within 6 months. CONCLUSIONS: This study suggests that the principles of minimally invasive plate osteosynthesis can be applied safely through posterior approach of the humerus to treat middle and distal third humeral fractures. This approach has the advantage of preserving the triceps anatomy and function facilitating rapid postoperative rehabilitation. PMID- 24241216 TI - Immunofluorescent localization of phosphoenolpyruvate carboxylase and ribulose 1,5-bisphosphate carboxylase/oxygenase proteins in leaves of C3, C 4 and C 3-C 4 intermediate Flaveria species. AB - An indirect immunofluorescence technique was used to determine the intercellular compartmentation of phosphoenolpyruvate (PEP) carboxylase and ribulose 1,5 bisphosphate carboxylase/oxygenase (Rubisco) proteins in leaves of five species of Flaveria, F. brownii A.M. Powell (C4), F. cronquistii A.M. Powell (C3), F. linearis Lag. (C3-C4 intermediate), F. floridana J.R. Johnston (C3-C4) and F. chloraefolia A. Gray (C3-C4). The results were compared with representative C3 and C4 plants. No strict intercellular compartmentation of either enzyme was observed in any of the five Flaveria species examined. Both carboxylase proteins were found throughout the leaf chlorenchyma of the C3 Flaveria, as was also the case in Nicotiana tabacum L. (C3). A similar distribution pattern was observed not only in the three C3-C4 intermediates, but in the C4 Flaveria as well. This distribution contrasted markedly with the localization patterns found in Zea mays L. (C4), where Rubisco was confined to bundle-sheath chloroplasts and PEP carboxylase to the mesophyll cytoplasm. PMID- 24241217 TI - Spatial relationships between uninfected and infected cells in root nodules of soybean. AB - In soybean (Glycine max (L.) Merr.) the uninfected cells of the root nodule are responsible for the final steps in ureide production from recently fixed nitrogen. Stereological methods and an original quantitative method were used to investigate the organization of these cells and their spatial relationships to infected cells in the central region of nodules of soybean inoculated with Rhizobium japonicum strain USDA 3I1B110 and grown with and without nitrogen (as nitrate) in the nutrient medium. The volume occupied by the uninfected tissue was 21% of the total volume of the central infected region for nodules of plants grown without nitrate, and 31% for nodules of plants grown with nitrate. Despite their low relative volume, the uninfected cells outnumbered the much larger infected cells in nodules of plants grown both without and with nitrate. The surface density of the interface between the ininfected and infected tissue in the infected region was similar for nodules in both cases also, the total range being from 24 to 26 mm(2)/mm(3). In nodules of plants grown without nitrate, all sampled infected cells were found to be in contact with at least one uninfected cell. The study demonstrates that although the uninfected tissue in soybean nodules occupies a relatively small volume, it is organized so as to produce a large surface area for interaction with the infected tissue. PMID- 24241218 TI - Structural organization of ultrarapidly frozen barley aleurone cells actively involved in protein secretion. AB - The ultrastructural organization of actively secreting barley (Hordeum vulgare L. cv. Himalaya) aleurone cells was examined using ultrarapid-freezing (<-10 000 degrees C s(-1)) followed by freeze-fracture and freeze-substitution. Our analysis indicates that much of the evidence supporting a direct pathway from the endoplasmic reticulum (ER) to the plasma membrane (i.e. bypassing the Golgi apparatus) for the secretion of alpha-amylase (EC 3.2.1.1) may not be valid. Cryofixed ER cisternae show no sign of vesiculation during active alpha-amylase secretion in gibberellic acid (GA3)-treated cells. At the same time, Golgi complexes are abundant and numerous small vesicles are associated with the edges of the cisternae. Vesicles appear to be involved in the delivery of secretory products to the plasma membrane since depressions containing excess membrane material appear there. Treatment with GA3 also induces changes in the composition of Golgi membranes; most notably, the density of intramembrane particles increases from 2700 MUm(-2) to 3800 MUm(-2) because of an increase of particles in the 3-8.5-nm size range. A slight decrease in 9-11-nm particles also occurs. These changes in membrane structure appear to occur as the Golgi complex becomes committed to the processing and packaging of secretory proteins. We suggest that secretory proteins in this tissue are synthesized in the abundant rough ER, packaged in the Golgi apparatus, and transported to the plasma membrane via Golgi derived secretory vesicles. Mobilization of reserves is also accompanied by dynamic membrane events. Our micrographs show that the surface monolayer of the lipid bodies fuses with the outer leaflet of the bilayer of protein-body membranes during the mobilization of lipid reserves. Following the breakdown of the protein reserves, the protein bodies assume a variety of configurations. PMID- 24241219 TI - Chloroplast development and the synthesis of chlorophyll and protochlorophyllide in Zostera transferred to darkness. AB - Intact plants and isolated leaves of Zostera capricornii Martens ex Aschers were transferred from daylight to darkness. Substantial amounts of chloropyll a and b continued to accumulate in immature and mature tissue in the same ratio as in the light and were incorporated into chlorophyll-protein complexes in the thylakoids. A small amount of protochlorophyllide also accumulated in immature tissue in the dark. Proplastids and immature chloroplasts continued to develop into mature chloroplasts in the dark in the normal manner but prolamellar bodies, which are a conspicuous feature of immature chloroplasts, took longer to disperse than in the light. Protochlorophyllide accumulation and prolamellar-body formation were not correlated. The results indicate that Zostera has a genetic capacity for dark chlorophyll synthesis which is expressed in immature and mature leaf tissue and enables this plant to continue synthesising chlorophyll and assembling chloroplasts at night. PMID- 24241220 TI - The role of carbon dioxide and oxygen in determining chlorophyll fluorescence quenching during leaf development. AB - Chlorophyll fluorescence emission at 680 nm (F680) and the rate of CO2 fixation were measured simultaneously in sections along the length of wheat and maize leaves. These leaves possess a basal meristem and show a gradation in development towards the leaf tip. The redox state of the primary electron acceptor, Q, of photosystem II was estimated using a non-invasive method. Distal mature leaf sections displayed typical F680 induction curves which were generally anti parallel with CO2 fixation and during which Q became gradually oxidised. In leaf base sections net assimilation of CO2 was not detectable, F680 quenched slowly and monotonously without displaying any of the oscillations typical of mature tissue and Q remained relatively reduced. Sections cut from mid-regions of the leaf showed intermediate characteristics. There were no major differences between the wheat and maize leaf in the parameters measured. The results support the hypothesis that generation of the transthylakoid proton gradient and associated ATP production is not a major limitation to photosynthesis during leaf development in either C3 or C4 plants. Removal of CO2 from the mature leaf sections caused little change in steady-state F680 and produced about 50% reduction of Q. When O2 was then removed, F680 rose sharply and Q became almost totally reduced. In immature tissue unable to assimilate CO2, removal of O2 alone caused a similar large rise in F680 and reduction of Q whilst removal of CO2 had negligible effects on F680 and the redox state of Q. It is concluded that in leaf tissue unable to assimilate CO2, either because CO2 is absent or the tissue is immature, O2 acts as an electron acceptor and maintains Q in a partially oxidised state. The important implication that O2 may have a role in the prevention of photoinhibition of the photochemical apparatus in the developing leaf is discussed. PMID- 24241221 TI - Stimulation of ethylene production and gas-space (aerenchyma) formation in adventitious roots of Zea mays L. by small partial pressures of oxygen. AB - Adventitious roots of two to four-weekold intact plants of Zea mays L. (cv. LG11) were shorter but less dense after extending into stagnant, non-aerated nutrient solution than into solution continuously aerated with air. Dissolved oxygen in the non-aerated solutions decreased from 21 kPa to 3-9 kPa within 24 h. When oxygen partial pressures similar to those found in non-aerated solutions (3, 5 and 12 kPa) were applied for 7 d to root systems growing in vigorously bubbled solutions, the volume of gas-space in the cortex (aerenchyma) was increased several fold. This stimulation of aerenchyma was associated with faster ethylene production by 45-mm-long apical root segments. When ethylene production by roots exposed to 5 kPa oxygen was inhibited by aminoethoxyvinylglycine (AVG) dissolved in the nutrient solution, aerenchyma formation was also retarded. The effect of AVG was reversible by concomitant applications of 1-aminocyclopropane-1 carboxylic acid, an immediate precursor of ethylene. Addition of silver nitrate, an inhibitor of ethylene action, to the nutrient solution also prevented the development of aerenchyma in roots given 5 kPa oxygen. Treating roots with only 1 kPa oxygen stimulated ethylene production but failed to promote gas-space formation. These severely oxygen-deficient roots seemed insensitive to the ethylene produced since a supplement of exogeneous ethylene that promoted aerenchyma development in nutrient solution aerated with air (21 kPa oxygen) failed to do so in nutrient solution supplied with 1 kPa oxygen. Both ethylene production and aerenchyma formation were almost completely halted when roots were exposed to nutrient solutions devoid of oxygen. Thus both processes require oxygen and are stimulated by oxygen-deficient surroundings in the 3-to 12-kPa range of oxygen partial pressures when compared with rates observed in air (21 kPa oxygen). PMID- 24241222 TI - Quantitative changes in calmodulin and NAD kinase during early cell development in the root apex of Pisum sativum L. AB - Calmodulin and NAD kinase were extracted from serial developmental sections of the pea root apex. Highly purified samples of calmodulin were assayed by NAD kinase activation, and whole-cell extracts were examined by two-dimensional polyacrylamide gel electrophoresis. Calmodulin was found to vary 17-fold in concentration over the apical 2 mm, being high in the region of the root cap and meristem, falling rapidly at the base of the meristem during early stages of rapid cell elongation. The rate of decline was different between stele and cortex. Except for a minor increase in concentration 2.5-5 mm from the apex, which coincides with the region of localised meristematic activity during initiation of lateral root primordia, the concentration of calmodulin remained at the lower level throughout the more basal sections of the apical 10 mm. In-vitro NAD-kinase activity was found to increase 17-fold per cell over the apical 30 mm, almost entirely as the result of an increase in calmodulin-dependent activity. Quantitative estimates of both calmodulin and NAD kinase were found to be highly dependent on extraction procedures. PMID- 24241223 TI - Diurnal and circadian rhythmicity in the expression of light-induced plant nuclear messenger RNAs. AB - The levels of nuclear mRNAs for three light-inducible proteins (light-harvesting chlorophyll a/b protein, small subunit of ribulose-1,5-bisphosphate carboxylase and early light-induced protein) have been analyzed under light-dark and constant light conditions. The levels of all three mRNAs have been found to vary considerably during the day, both under ligh-dark and under constant light conditions, demonstrating the existence of diurnal and circadian rhythmicity in the expressionoof these nuclear-coded plant proteins. The levels of two of these mRNAs have been found to be enhanced 2 h before the beginning of illumination when active phytochrome levels are still low. PMID- 24241224 TI - Purification and characterization of phosphoribulokinase from wheat leaves. AB - Homogeneous phosphoribulokinase (PRK; ATP: D-ribulose-5-phosphate 1 phosphotransferase, EC 2.7.1.19) was isolated from wheat leaves with a specific activity of 15 MUkat mg(-1) protein. The purification included ammonium sulfate cuts, isoelectric precipitation, and hydrophobic and affinity chromatography on pentylagarose and Blue Sepharose CL 6B, respectively. Gel filtration of the purified enzyme yielded a 83000 Da protein. Subunits of about 42000 Da were estimated from sodium dodecyl sulfate-polyacrylamide gels. Wheat leaf PRK was stable for at least four weeks when stored at 4 degrees C. Saturation curves for ribulose 5-phosphate (Ru5P) and ATP followed Michaelis-Menten kinetics (K m values: K m Ru5P=50-80 MUM; K m ATP=70 MUM). The saturation curve for MgCl2 was sigmoidal (half-maximal velocity <0.5 mM). The affinity for Ru5P, ATP and Mg(2+) was not affected by pH changes comparable to pH shifts in the stroma. In contrast to chloroplast fructose-bisphosphatase (Zimmermann et al. 1976, Eur. J. Biochem. 70, 361-367) the affinity for ligands remained unchanged in the dithiothreitol activated and in the non-activated state. The activity of PRK was increasingly sensitive to inhibition by 3-phosphoglyceric acid with decreasing pH below pH 8.0. PMID- 24241225 TI - The action of exogenous abscisic and gibberellic acids on gene expression in germinating castor beans. AB - Exogenously applied abscisic acid inhibits isocitrate-lyase activity of the endosperm during germination of castor-bean seeds. Amounts of isocitrate-lyase mRNA have been estimated by immunoprecipitation of in-vitro-translated polypeptide products. Exogenous abscisic acid leads to an inhibition of isocitrate lyase-mRNA accumulation. A large proportion of this effect of the growth factor may be accounted for by its action in inhibiting the overall accumulation of ribosomal RNA and total mRNA. However, the effect of abscisic acid on protein synthesis is not general, as the production of some mRNAs was stimulated. The major mRNA stored in the dry seed, coding for a 25600-Mr polypeptide that normally disappears within the first 12 h of germination, exhibited high levels in abscisic-acid-treated endosperms throughout the germination period. Three complementary DNA clones, of which two clones are complementary to isocitrate lyase, have been used to measure levels of transcripts during seed germination. The accumulation of both transcripts was inhibited by exogenous abscisic acid. The data strongly indicate that the action of abscisic acid on isocitrate lyase synthesis is either to inhibit the transcription, or to increase the transcript turnover. Exogenous gibberellic acid is able to counteract the inhibitory effects of abscisic acid. PMID- 24241226 TI - The major albumin protein from pea (Pisum sativum L.) : Localisation by immunocytochemistry. AB - The major albumin protein in storage parenchyma tissue of developing peas has been localised at an ultrastructural level by immunocytochemistry. Tissue was fixed in buffered aldehyde and embedded in LR White resin which was polymerised by addition of catalyst. Sections were labelled by the indirect method of absorption of Protein A-gold to specifically bound antibodies. This method gives high levels of specific labelling on sections which retain good ultrastructural preservation and have high contrast after conventional staining. The albumin is located throughout the cytoplasm although no labelling was found associated with the endoplasmic reticulum, Golgi apparatus, vacuoles-protein bodies or other organelles. PMID- 24241227 TI - Application of X-ray microanalysis to cell suspensions of oil palm (Elaeis guineensis Jacq.). AB - X-ray microanalysis has been used to determine the elemental composition of oil palm (Elaeis guineesis) cell suspensions without the use of cryoprotectants. Results based on individual cells were gathered over a typical growth cycle of 14 d. During the log phase (5-7 d) there is an increase in the number of cells containing high concentrations of both K (400 mmol kg(-1) dry weight) and P (400 mmol kg(-1) dry weight). Morphologically these cells had thin cell walls and were frequently joined to other cells (two to five cells per clump). PMID- 24241228 TI - The pyridine-nucleotide cycle in tobacco Enzyme activities for the de-novo synthesis of NAD. AB - The enzyme activities of the pyridine-nucleotide cycle, which transform nicotinic acid mononucleotide (NaMN) into NAD, have been characterized. The investigations were based on the extraction of protein, its purification on disposable gel filtration columns, and determination of the enzymatic activities by high performance liquid chromatography techniques. The latter technique avoided the synthesis and use of radioactive precursors. The NaMN-adenylyltransferase which converts NaMN into NaAD (nicotinic acid adenine dinucleotide) and NAD-synthetase which converts NaAD into NAD were characterized by their kinetic parameters and their specific activities in different tobacco tissues. This is the first report on NAD-synthetase from tissue of a higher plant. It was found that NAD-synthetase accepted both glutamine and asparagine for the amide transfer. Adenylyltransfer also occured with nicotinamide mononucleotide (NMN) which was transformed to NAD, whereas the glutamine-dependent amidation was only observed with NaAD. Thus, an additional route for the synthesis of NAD (NaMN->NMN->NAD) obviously does not exist. A comparison of the enzyme activities in tobacco tissues with different capacities for the synthesis of nicotine showed that, in contrast to quinolinic acid phosphoribosyltransferase whose activity was strictly correlated with the nicotine content, only NaMN-adenylyltransferase showed a smooth correlation, whereas NAD-synthetase was not affected at all. PMID- 24241229 TI - Phycomyces: Phototropism and light-growth response to pulse stimuli. AB - The relationship between phototropism and the light-growth response of Phycomyces blakesleeanus (Burgeff) sporangiophores was investigated. After dark adaptation, stage-IVb sporangiophores were exposed to short pulses of unilateral light at 450 nm wavelength. The sporangiophores show a complex reaction to pulses of 30 s duration: maximal positive bending at 3.10(-4) and 10(-1) J m(-2), but negative bending at 30 J m(-2). The fluence dependence for the light-growth response also is complex, but in a different way than for phototropism; the first maximal response occurs at 1.8.10(-3) J m(-2) with a lesser maximum at 30 J m(-2). A hypertropic mutant, L85 (madH), lacks the negative phototropism at 30 J m(-2) but gives results otherwise similar to the wild type. The reciprocity rule was tested for several combinations of fluence rates and pulse durations that ranged from 1 ms to 30 s. Near the threshold fluence (3.10(-5) J m(-2)), both responses increase for pulse durations below 67 ms and both have an optimum at 2 ms. At a fluence of 2.4.10(-3) J m(-2), both responses decrease for pulse durations below 67 ms. The hypertropic mutant (madH), investigated for low fluence only, gave similar results. In both strains, the time courses for phototropism and light growth response, after single short pulses of various durations, show no clear correlation. These results imply that phototropism cannot be caused by linear superposition of localized light-growth responses; rather, they point to redistribution of growth substances as the cause of phototropism. PMID- 24241230 TI - Porphyra nereocystis: A dual-daylength seaweed. AB - Conchospores from the perennial conchocelis phase of the annual, epiphytic, marine red alga Porphyra nereocystis Anderson, which in nature lives on the large annual kelp Nereocystis luetkeana (Mertens) Postels et Ruprecht, are released in culture only in response to a short-day photoperiod treatment followed by a long day treatment. Each treatment requires a minimum of three to four weeks and is enhanced by lower temperature during the second photoperiod treatment. To our knowledge P. nereocystis is the first known dualdaylength seaweed and requires a short-day-longday treatment for completion of its life cycle. This stringent environmental control of its reproduction appears to be an adaptation to coordinate conchospore production with the seasonal availability of its host kelp Nereocystis. PMID- 24241231 TI - Transcription of a legumin gene from pea (Pisum sativum L.) in vitro. AB - The transcriptional activity of the pea legumin gene leg A in the HeLa cell lysate in-vitro transcription system has been assayed. Labelled transcripts were examined by hybridisation to restriction fragments of Leg A, and by glyoxalation followed by agarose gel electrophoresis. Although the legumin gene was not transcribed efficiently, transcripts were shown to be produced from the correct region of Leg A, and analysis by S1 nuclease mapping was used to show that the transcription start was the same as in vivo. The transcripts produced in vitro did not extent over the whole coding sequence of the gene; termination of transcripts occurred in a semi-random fashion. Transcription of templates truncated at their 3' ends (i.e. in coding sequence) showed that discrete transcripts were produced from the start to restriction sites at approx. +520 and +900 bases. Transcription of templates truncated at their 5' ends showed that sequences upstream of-97 bases relative to the transcription start had no appreciable effect on transcription in vitro. PMID- 24241232 TI - Amino-acid biosynthesis in the cotyledons of Sinapis alba L. in darkness and far red light studied by deuterium labelling and mass spectrometry. AB - The incorporation of deuterium from deuterium oxide into the free amino acids of the cotyledons of Sinapis alba L. was studied by gas chromatography-mass spectrometry and was similar, both qualitatively and quantitatively, after incubation of the seedlings in darkness or far-red light. The results support studies which show that phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) is synthesised de novo, rather than activated, in response to far-red light. PMID- 24241233 TI - Microbial associations of soil types. AB - Microorganisms are characterized by wide ranges of distribution. Some groups, however, are known to have zones of active proliferation, and the development of specific populations in discrete zones results in rather specific microbial associations in some soil types. The soils formed in warm climates are richer in microorganisms and contain more bacilli and actinomycetes. The spectrum of dominant microbial groups varies in different soil types. PMID- 24241234 TI - Microbiological basis of phosphate removal in the activated sludge process for the treatment of wastewater. AB - Several strains resembling members of theAcinetobacter-Moraxella-Mima group of bacteria were isolated from activated sludge-type sewage treatment plants designed for phosphate removal. The bacteria are obligate aerobes but utilize as carbon and energy sources low-molecular intermediates generated anaerobically, particularly acetate and ethanol. These bacteria can be shown to be responsible for the phosphate luxury uptake occurring in these treatment plants. The bacteria are physiologically unusual in that they perform luxury uptake of phosphates in a complete growth medium. Phosphate release occurs on addition of a carbon source to the carbon-starved bacteria, lowering pH or both. The bacteria persist in the system by virtue of their ability to form floc. PMID- 24241235 TI - The microbiology and biogeochemistry of the Dead Sea. AB - The Dead Sea is a hypersaline water body. Its total dissolved salts content is on the average 322.6 gm/liter. The dominant cation is Mg (40.7 gm/liter), followed by Na (39.2 gm/liter), Ca (17 gm/liter) and K (7 gm/liter). The major anion is Cl (212 gm/liter), followed by Br (5 gm/liter); SO4 and HCO3, are very minor. The lake contains a limited variety of microorganisms and no higher organisms. The number of recorded species is very low, but the total biomass is reasonably high (about 10(5) bacteria/ml and 10(4) algal cells/ml). The indigenous flora is comprised mainly of obligate halophylic bacteria, such as the pink, pleomorphicHalobacterium sp., aSarcina-like coccus, and the facultative halophilic green alga,Dunaliella. Sulfate reducers can be isolated from bottom sediments. Recently a unique obligate magnesiophile bacteria was isolated from Dead Sea sediment. Several of the Dead Sea organisms possess unusual properties. TheHalobacterium sp. has extremely high intercellular K(+) concentration (up to 4.8M) and extraordinary specificity for K(+) over Na. TheDunaliella has very high intracellular concentration of glycerol (up to 2.1M). The microorganisms exert marked influence on some biogeochemical processes occurring in the lake, such as the control of the sulfur cycle and the formation and diagenesis of organic matter in the sediments. The Dead Sea is an excellent example of the development of two different mechanisms for adjusting to a hostile environment. The algae adjust to the high salinity by developing a mechanism for the exclusion of salts from the intracellular fluid and using glycerol for osmotic regulation. On the other hand, the bacteria adapt to the environment by adjusting their internal inorganic ionic strength, but not composition, to that of the medium. The problem of population dynamics and limiting factors for algal and bacterial productivity are discussed in view of the total absence of zooplankton and other consumers other than bacteria. PMID- 24241236 TI - Binding of mercuric and other heavy metal ions by microbial growth media. AB - Ion-specific electrodes were used to study the binding of Hg(2+), Pb(2+), Cu(2+), and Cd(2+) ions to widely used bacterial growth media (Nutrient broth, trypticase soy broth, the medium of Foot and Taylor [6] and of Nelsonet al.[12]) and to media components [yeast extract, peptone, tryptone, proteose peptone, and casamino acids (acid hydrolyzed casein)]. Volatilization of Hg(2+) from aqueous solutions could be prevented by any of the growth media or their components. All media bound large amounts of Hg(2+), Pb(2+), and Cu(2+), but much less Cd(2+). Of the media components, casamino acids showed the most binding activity for all metal ions; the relative affinity of other media components to different ions varied with the cation studied. In general, the Irving-Williams [8] series for cation affinity to organic ligands was followed: Hg(2+)>Pa(2+)? Cu(2+)? Cd(2+).After adding 20 ppm of Hg(2+), Pb(2+), or Cu(2+) (concentrations inhibitory to the growth of most microorganisms) to the growth media, 80 ppb or less remained as free cations in the solution. This might suggest that such ions enter bacterial cells as organic complexes, or that bacterial cells can compete successfully with growth media for the bound ions. PMID- 24241237 TI - Health-related quality of life in kidney transplant patients and non-renal replacement therapy patients with chronic kidney disease stages 3b-4. AB - BACKGROUND: Patients with a functioning kidney transplant (Tx) and patients with chronic kidney disease (CKD) not in dialysis report better health-related quality of life (HRQoL) than patients requiring dialysis, but poorer than the general population. HRQoL is associated with kidney function, but it is unknown whether the kidney function per se is the main determinant of HRQoL. The aim of this study was to compare the HRQoL in 2 groups of patients with CKD: 1 group with native kidneys only (non-renal replacement therapy [non-RRT] group) and 1 group with a functioning kidney transplant (Tx group). MATERIAL/METHODS: The study was designed as a paired cross-sectional single-center study including 38 stable Tx patients age- and gender-matched with 38 non-RRT patients with the same kidney function, CKD stages 3b-4. HRQoL was evaluated using the short form-36 (SF-36) and a visual analogue scale (VAS). RESULTS: The multi-item scales and summary scores in SF-36 were not significantly different between the 2 groups of patients or the general Norwegian population. However, the non-RRT group scored significantly better than the Tx group when HRQoL was evaluated by VAS. The main determinants for HRQoL in both groups of patients were depression estimated by Beck depression inventory scores and comorbidity expressed by Davies comorbidity index scores. CONCLUSIONS: HRQoL evaluated by SF-36 in a group of stable Tx patients in CKD stages 3b-4 is comparable to that of a group of non-RRT patients. However, HRQoL VAS was better in the non-RRT group, suggesting that VAS and SF-36 may evaluate different aspects in HRQoL in the same group of patients. PMID- 24241238 TI - Mechanistic studies of transition metal-mediated C-C bond activation. AB - Organometallic compounds have been found to be of use in cleaving C-C bonds, as strong metal-carbon bonds can be formed to replace the bond that is broken. Studies of the mechanism of C-C cleavage can provide insight into how these bonds can be cleaved, and can give valuable information that can be used to develop new strategies for breaking C-C bonds and using the products in catalysis. In this chapter, we will examine a number of systems where mechanistic information has been obtained in C-C cleavage. PMID- 24241239 TI - Natural and orthogonal model for estimating gene-gene interactions applied to cutaneous melanoma. AB - Epistasis, or gene-gene interaction, results from joint effects of genes on a trait; thus, the same alleles of one gene may display different genetic effects in different genetic backgrounds. In this study, we generalized the coding technique of a natural and orthogonal interaction (NOIA) model for association studies along with gene-gene interactions for dichotomous traits and human complex diseases. The NOIA model which has non-correlated estimators for genetic effects is important for estimating influence from multiple loci. We conducted simulations and data analyses to evaluate the performance of the NOIA model. Both simulation and real data analyses revealed that the NOIA statistical model had higher power for detecting main genetic effects and usually had higher power for some interaction effects than the usual model. Although associated genes have been identified for predisposing people to melanoma risk: HERC2 at 15q13.1, MC1R at 16q24.3 and CDKN2A at 9p21.3, no gene-gene interaction study has been fully explored for melanoma. By applying the NOIA statistical model to a genome-wide melanoma dataset, we confirmed the previously identified significantly associated genes and found potential regions at chromosomes 5 and 4 that may interact with the HERC2 and MC1R genes, respectively. Our study not only generalized the orthogonal NOIA model but also provided useful insights for understanding the influence of interactions on melanoma risk. PMID- 24241240 TI - Gene-gene and gene-environment interactions in ulcerative colitis. AB - Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case-Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high-order interactions. Exploratory genotype correlations with UC sub-phenotypes [extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)] were conducted. The combination of 133 UC loci yielded good UC risk predictability [area under the curve (AUC) of 0.86]. A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P = 3.26E-05). Explained UC variance increased from 37 to 42 % after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high-order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene-gene and gene-environment interactions. PMID- 24241242 TI - Biodefense: trends and challenges in combating biological warfare agents. PMID- 24241243 TI - Advances in diagnostic and therapeutic colonoscopy. AB - PURPOSE OF REVIEW: We review current studies on endoscopic and technologic advances for the detection and treatment of colorectal neoplasia. RECENT FINDINGS: Improvements in adenoma detection have been shown to be possible with the use of high definition white light as well as water-related methods such as water exchange. Use of cap assist colonoscopy, when combined with water-related methods, has recently been shown to also improve the detection of adenomas. Narrow band imaging and confocal laser endomicroscopy may have an advantage of offering endoscopists the ability to make an 'optical diagnosis' with the possibility of discarding nonadenomatous tissue. Furthermore, educational interventions aimed at improving adenoma detection may have lasting effects on endoscopists' adenoma detection rates. Lastly, endoscopic mucosal resection and endoscopic submucosal dissection are being applied for the treatment of large colorectal polyps, obviating the need for surgery in most instances. However, further studies are needed to establish the optimal methods for polyp resection. SUMMARY: Advances in endoscopic technology are being shown to enhance the detection of early cancers and precancerous lesions. However, these tools may be supplementary to a high-quality colonoscopy using excellent techniques, factors that are now being implemented in training programs. PMID- 24241241 TI - A molecular pathway for the egress of ammonia produced by nitrogenase. AB - Nitrogenase converts N2 to NH3, at one face of an Fe-Mo-S cluster (FeMo-co) buried in the protein. Through exploration of cavities in the structures of nitrogenase proteins, a pathway for the egress of ammonia from its generation site to the external medium is proposed. This pathway is conserved in the three species Azotobacter vinelandii, Klebsiella pneumoniae and Clostridium pasteurianum. A molecular mechanism for the translocation of NH3 by skipping through a sequence of hydrogen bonds involving eleven water molecules and surrounding aminoacids has been developed. The putative mechanism requires movement aside of some water molecules by up to ~ 1A. Consistent with this, the surrounding protein is comprised of different chains and has little secondary structure: protein fluctuations are part of the mechanism. This NH3 pathway is well separated from the water chain and embedded proton wire that have been proposed for serial supply of protons to FeMo-co. Verification procedures are suggested. PMID- 24241244 TI - Global progress towards eliminating gastrointestinal helminth infections. AB - PURPOSE OF REVIEW: To highlight the gastrointestinal helminths in the context of renewed global commitment to control or eliminate neglected tropical diseases in the coming decade. RECENT FINDINGS: Two key documents, namely the 2012 London Declaration for Neglected Tropical Diseases and the 2013 World Health Assembly resolution, emphasize the importance of mass drug administration (MDA) for controlling several key neglected tropical diseases. These documents, together with the Global Burden of Disease Study 2010, establish the major gastrointestinal helminth infections, including the soil-transmitted helminthiases - ascariasis, trichuriasis, hookworm, and strongyloidiasis - in addition to the intestinal and liver fluke infections, as some of the most important gastrointestinal infections of humankind. Current MDA approaches using single-dose albendazole or mebendazole are effective for ascariasis, less so for other soil-transmitted helminth infections. Expanded use of albendazole in combination with ivermectin would ensure improved drug efficacies against trichuriasis and strongyloidiasis. There is no effective elimination strategy for targeting hookworm and liver and intestinal fluke infections through current MDA approaches. SUMMARY: The global community must expand current MDA efforts, while simultaneously developing additional drugs, diagnostics, and vaccines alongside better utilizing transmission dynamics and modeling, if it is to successfully meet the goals and targets established by policymakers. PMID- 24241245 TI - Fecal microbiota transplantation: facts and controversies. AB - PURPOSE OF REVIEW: To review the current evidence on fecal microbiota transplantations (FMTs) for recurrent Clostridium difficile infections (CDIs), metabolic syndrome and inflammatory bowel disease. RECENT FINDINGS: Recently, a randomized trial confirmed the efficacy of this treatment strategy in patients with recurrent CDI. For other disorders, evidence is still limited. To date, studies have been performed to try and influence the course of metabolic syndrome and inflammatory bowel disease. SUMMARY: There is increasing interest in the role of altered microbiota in the development of a myriad of diseases. Together with new insights comes an interest in influencing this altered microbiota as a potential target for therapy. FMTs are effective against recurrent CDI, a disorder caused by disruption of the normal microbiota. Restoration of intestinal flora and thereby restoration of colonization resistance is thought to be the mechanism responsible for cure. With the developments in FMT and the extension of this treatment modality to both intestinal and extra-intestinal diseases, a new field of targeted therapy awaits. The ultimate goal is the development of powerful probiotic regimens that can replace FMT. Currently, FMT should only be given in a strict experimental setting for other conditions than CDI. PMID- 24241247 TI - Effectiveness of influenza vaccine in patients on hemodialysis--a review. AB - The influenza virus is one of the most common causes of viral respiratory tract infections. Some chronic diseases predispose to a severe course of the disease and increase the risk of complications and death. To minimize the risk of infection and complications, care of patients with increased risk should include prophylactic measures such as the administration of a seasonal influenza vaccine. An influenza vaccine is the best and cheapest method of influenza prevention. It is indicated for patients with chronic kidney disease, both during conservative treatment and renal replacement therapy. Many studies that have assessed the efficacy of an influenza vaccine in patients on hemodialysis have found that immune deficiency predisposes these patients to infection and a severe course of the disease. Because the immune response to a standard influenza vaccine in this population is weak, the studies covered many aspects of vaccination, including the need for a booster dose. Unlike in a healthy population, the efficacy of an influenza vaccine in patients on hemodialysis might be insufficient; however, the vaccine is still able to induce immunity in a significant number of patients. Considering the latest data and the results of studies described above, the recommendation of a seasonal influenza vaccine should be obligatory in all hemodialysis patients. This paper is based on original articles available from Medline database. The most recent and most significant literature on the influenza vaccine in patients on hemodialysis has been reviewed. PMID- 24241246 TI - The role of monocyte phenotype switching in peri-procedural myocardial injury and its involvement in statin therapy. AB - Peri-procedural myocardial injury, which is associated with worse long-term clinical outcome, is a common complication related to inflammatory pathogenetic mechanisms. Monocytes and macrophages play key roles in the initiation and progression of atherosclerosis. Recent studies have demonstrated that monocytes in human peripheral blood are heterogeneous, including CD14+CD16- monocytes and CD14+CD16+ monocytes. Several lines of evidence suggested that CD14+CD16+ monocytes might contribute to the accelerated atherosclerosis. In view of the heightened appreciation of the heterogeneity of circulating monocytes, we hypothesized that an up-shifting subset of CD14+CD16+ monocytes might be induced by percutaneous coronary intervention (PCI), which subsequently leads to peri procedural myocardial injury. Moreover, statins loading before PCI could exert anti-inflammatory effects partly by modulating monocyte phenotype and thus prevent peri-procedural myocardial injury. PMID- 24241248 TI - Gadolinium oxysulfide nanoparticles as multimodal imaging agents for T2-weighted MR, X-ray tomography and photoluminescence. AB - We have synthesized gadolinium oxysulfide nanoparticles (NPs) doped with other lanthanides (Eu(3+), Er(3+), Yb(3+)) via a hydroxycarbonate precursor precipitation route followed by a sulfuration process under a H2S-Ar atmosphere at 750 degrees C in order to propose new multimodal nanoplatforms for Magnetic Resonance (MR), X-ray and photoluminescence imaging. Gd2O2S:Eu(3+) NPs strongly absorb near UV (~ 300-400 nm) and re-emit strong red light (624 nm). They can be easily internalized by cancer cells, and imaged by epifluorescence microscopy under excitation in the NUV (365 nm). They are not cytotoxic for living cells up to 100 MUg mL(-1). Consequently, they are well adapted for in vitro imaging on cell cultures. Gd2O2S:Eu(3+) NPs also show strong transverse relaxivity and strong X-ray absorption allowing their use as contrast agents for T2-weighted MRI and X-ray tomography. Our study shows that Gd2O2S:Eu(3+) NPs are considerably better than commercial Ferumoxtran-10 NPs as negative contrast agents for MRI. Upconversion emission of Gd2O2S:Er; Yb (1; 8%) NPs under infrared excitation (lambda(ex) = 980 nm) shows mainly red emission (~ 650-680 nm). Consequently, they are more specifically designed for in vivo deep fluorescence imaging, because both excitation and emission are located inside the "transparency window" of biological tissues (650-1200 nm). Magnetic relaxivity and X-ray absorption behaviors of Gd2O2S:Er; Yb NPs are almost similar to Gd2O2S:Eu(3+) NPs. PMID- 24241249 TI - Genotoxic damage in the oral mucosal cells of subjects carrying restorative dental fillings. PMID- 24241250 TI - Mitochondrial toxin betulinic acid induces in vitro eryptosis in human red blood cells through membrane permeabilization. AB - Betulinic acid (BA), a compound isolated from the bark of white birch (Betula pubescens), was reported to induce apoptosis in many types of cancer through mitochondrial dysfunction with low side effects in normal cells. Because of these features, BA is regarded as a potential anti-cancer agent. However, the effect of BA on the induction of cell death in human erythrocytes remains unknown. Given that BA is a mitochondrial toxin and mitochondria are the central cell death regulator, we hypothesized that BA is unable to elicit apoptosis (also known as eryptosis or erythroptosis) in human erythrocytes devoid of mitochondria. This study therefore tried to determine the in vitro effect of BA on the induction of eryptosis/erythroptosis. Contrary to our prediction, BA caused phosphatidylserine externalization, increase in cellular Ca(2+) ion concentration ([Ca(2+)]i) and eryptosis/erythroptosis in human erythrocytes with a lethal dose larger than that in cancer lines. Mechanistically, the rise of [Ca(2+)]i seems not to be the only key mediator in the BA-mediated eryptosis/erythroptosis because depletion of external Ca(2+) and use of Ca(2+) channels blockers could not eliminate the BA's effect. Also, BA was able to elicit discocyte-echinocyte transformation and release calcein from the RBC ghosts in a way similar to digitonin through membrane permeabilization. Collectively, we report here for the first time that BA induced eryptosis/erythroptosis in human erythrocytes through Ca(2+) loading and membrane permeabilization. PMID- 24241253 TI - Head and neck surgical patients; is it time for a bridle era? AB - Early enteral feeding is vital for successful outcomes in patients who have undergone open pharyngeal surgery, with nasogastric tube (NGT) feeding being a safe and accepted method of providing enteral nutrition in the short-term. Securing the NGT is key to ensure adequate caloric consumption and avoid the potential complications of re-siting the tube. The aim of this study was to compare the efficacy of utilising an anterior septal suture to a bridle system for NGT fixation. A sheep's head model was used to represent the nasal cavity of post-operative patients and a fine-bore NGT was passed. The NGT was secured with either an anterior septal suture or bridle system. A pulley system of weights was applied until the NGT slipped or snapped. Each weight and condition was investigated five times. The anterior and posterior septum were examined for evidence of damage for each condition. At 5 kg the anterior septal suture allowed the NGT to slip and the tube began to become distorted. At 5.5 kg the anterior septal suture snapped the NGT. In comparison, the bridle system was able to sustain a weight up to 15.5 kg (Fisher's exact test, p = 0.0079). There was no evidence of damage to the anterior or posterior septum for each condition. The bridle system was able to fix the NGT without slippage or damage at higher weights than the anterior septal suture. This suggests there may be potential benefits of stronger NGT fixation with reduced tube damage using bridle systems in patients, but further research is required in this domain. PMID- 24241254 TI - Scientific hero: Dr. James E. K. Hildreth. PMID- 24241252 TI - Combined type IIIB with bilateral type I thyroplasty for pitch lowering with maintenance of vocal fold tension. AB - To evaluate type IIIB thyroplasty using the excised larynx bench apparatus and determine how altering vocal fold contour by performing bilateral medialization of the inferior vocal fold affects phonation. This procedure could be performed in patients for whom pitch lowering is desirable, such as female-to-male transsexuals or male patients with mutational falsetto in whom intensive voice therapy was insufficient. Aerodynamic, acoustic, and high-speed videokymographic data were collected for nine larynges at three subglottal pressure inputs for each of three conditions: normal; type IIIB thyroplasty; and combined type IIIB with modified bilateral type I thyroplasty intended to create a more rectangular glottal configuration. Each larynx served as its own control. Phonation threshold flow (p = 0.005), phonation threshold power (p = 0.031), and airflow varied across conditions with highest values for type IIIB thyroplasty and lowest for the combined procedure. Fundamental frequency was significantly different (p < 0.001), decreasing by approximately 100 Hz from control to type IIIB trials, and then by approximately 15 Hz from IIIB to combined procedure trials. Vibratory amplitudes and intrafold phase difference were highest for type IIIB trials. Addition of bilateral inferior medialization to type IIIB thyroplasty provided some further decrease in frequency, but mostly served to increase tension, reduce airflow, and produce a vibratory pattern which more closely mirrored control trials. Exploration of this combined procedure in patients may be warranted if not completely satisfied with the results from type IIIB thyroplasty alone. PMID- 24241255 TI - Making a difference: steps to develop a research pipeline in Puerto Rico. PMID- 24241257 TI - Reproductive Health Assessment After Disasters: embedding a toolkit within the disaster management workforce to address health inequalities among Gulf-Coast women. AB - Gulf Coast women are especially vulnerable to the effects of disaster and for many this vulnerability is compounded by existing poor health-related quality of life. Post-Hurricane Isaac, a baseline survey battery utilizing the Reproductive Health Assessment After Disasters (RHAD) Toolkit, the Medical Outcomes Study Social Support Survey, and the Edinburgh Postnatal Depression Scale were used quantitatively to assess reproductive health risks, services, and outcomes and to explore the psychosocial effects of disaster among pregnant and postpartum women aged 18-45 years (N=300). The pilot study included trained community health workers and patient navigators to implement a community needs assessment in Southeast Louisiana. The community health navigation corps administered RHAD and the brief psychosocial battery to gain a closer understanding of post-disaster reproductive health needs. Findings demonstrate the importance of making a transition from patient navigation into disaster management in order to reduce fragmentation in health care systems and to implement innovative approaches in survey methodology. PMID- 24241256 TI - Different levels of HIV DNA copy numbers in cerebrospinal fluid cellular subsets. AB - Inequities in the incidence of HIV infection and AIDS with continued persistence of HIV-associated neurocognitive disorders (HAND) exist in populations in Hawaii (HI) and Puerto Rico (PR). We previously reported that peripheral monocyte HIV DNA levels are high in patients in Hawaii with HAND and we now hypothesize that similar findings would be observed in the cerebrospinal fluid (CSF) cellular subsets. Cerebrospinal fluid cells were obtained from patients from PR and HI undergoing neurocognitive testing and sorted into monocytes (CD14+) and lymphocytes (CD14-) and HIV DNA was measured. From six PR subjects (three HAND, three normal cognition, NC) and six HI subjects (three HAND, three NC), HIV DNA burden in CD14+ cells was higher in HAND than NC patients; NC patients had higher HIV DNA burden in CD14-cells versus HAND. Differences in HIV DNA burden in particular CSF cellular subsets suggest that HIV DNA burden may play a role in HAND neuropathogenesis. PMID- 24241258 TI - Hepatitis-C multimedia prevention program in poor Hispanic HIV-infected injecting drug users: six months after intervention. AB - BACKGROUND: In order to prevent the spread of the hepatitis C virus (HCV) amongst Hispanic injection drug users (IDUs), we developed, validated, and implemented a multimedia educational intervention program. METHODS: A pre-post intervention study design was used to evaluate long-lasting knowledge and behavior changes in a group of 88 low-income Hispanic HIV-infected IDUs. Pre-intervention data was compared with data measured six months after the intervention. RESULTS: A significant increase in the awareness regarding HCV clinical manifestations, HCV risky behaviors, HCV prevention practices, and HIV/HCV co-infection synergisms was observed in the group six months post-intervention. CONCLUSION: Our study confirms the long-lasting benefits of multimedia based intervention programs for disseminating HCV prevention strategies in IDUs. Preventive educational approaches that use images, figures, and animations tools can be recommended to target and tailor interventions for vulnerable populations. PMID- 24241259 TI - Importance of vitamin D and vitamin D levels status in Puerto Ricans. AB - There is growing and compelling evidence demonstrating the extra-skeletal role of vitamin D and the importance of maintaining adequate levels of this nutrient. Currently, there is very limited information available on the vitamin D status in children and adults in underserved groups, including Puerto Ricans. We assessed the vitamin D status of 4,090 Puerto Ricans living in six geographical regions in the island. Only 31.5% of the studied population had sufficient vitamin D levels (>30 ng/ml). The 18-39 year age group and the females showed inadequate (<30 ng/ml) levels of vitamin D (76.9% and 69.8%, respectively). Participants aged 60 or older showed the highest mean values of serum 25(OH)D (28.8 ng/ml) and the highest percentage (37.1%) of sufficient levels (>30 ng/ml). Future studies are certainly warranted to understand the prevalence of vitamin D deficiency and influencing factors (including obesity) in Puerto Ricans. PMID- 24241260 TI - A community-based pilot study of a diabetes pharmacist intervention in Latinos: impact on weight and hemoglobin A1c. AB - Type 2 diabetes disproportionately affects Latinos increasing their risk of diabetes-related complications. This study used a randomized controlled design with a community-based approach to evaluate the impact of a culturally tailored pharmacist intervention on clinical outcomes in Latino diabetics. The intervention included a focused discussion and two individual pharmacist counseling sessions on medication, nutrition, exercise, and self-care to promote behavior changes. Sessions were culturally adapted for language, diet, family participation, and cultural beliefs. Clinical outcomes were measured at baseline and three months. Nineteen intervention and 24 control participants completed the study. Mean BMI reduction was greater for intervention than for control group participants (-0.73 +/- 0.07 kg/m2 versus + 0.37 +/- 0.02 kg/m2 p<.009 respectively). Hemoglobin A1c was significantly reduced by 0.93 +/- 0.45% in the intervention group only. There was no significant difference in blood glucose, blood pressure, or lipid levels. An innovative culturally-sensitive pharmacist intervention improved selected clinical outcomes among Latino diabetics. PMID- 24241261 TI - Fractionated Ocimum gratissimum leaf extract inhibit prostate cancer (PC3.AR) cells growth by reducing androgen receptor and survivin levels. AB - In this study, the antiproliferative activity of the organic solvent-soluble and aqueous extracts of Ocimum gratissimum leaf against the prostate cancer cells PC3.AR were evaluated by their inhibitory effects on the Androgen Receptor (AR) and Survivin protein. Two organic solvent-soluble extracts P2 and P3-2, and a water- soluble extract, PS/PT1, were found to reduce AR and Survivin levels in a time-dependent manner. In addition, extract PS/PT1, also exhibited the inhibitory activity in a dose-dependent manner. This is the first time that the inhibitory eff ects of O. gratissimum extracts have been evaluated on the Androgen Receptor (AR) and Survivin protein. The results encouraged the further studies of O. gratissimum as a potential treatment of prostate cancer. PMID- 24241262 TI - Apolipoprotein E4 prevents growth of malaria at the intraerythrocyte stage: implications for differences in racial susceptibility to Alzheimer's disease. AB - Apolipoprotein E 4 (ApoE 4) has been linked to pathogenesis of Alzheimer's disease and has been suggested to be maintained through evolutionary pressure via a protective role in malaria infection. We evaluated Plasmodium falciparum viability at the intraerythrocyte stage by exposure to plasma from human subjects with ApoE 4/4 or ApoE 3/3. Plasma samples from ApoE 4/4 but not ApoE 3/3 donors inhibited growth and disrupted morphology of P. falciparum. Evolutionary history is characterized by war between pathogenic microorganisms and defense mechanisms countering their pathogenicities. ApoE 4 frequency is highest in sub-Saharan Africa and other isolated populations (e.g., Papua New Guinea) that exhibit endemic malaria. High ApoE frequency may offer selective advantage protecting against some infectious diseases (e.g., Plasmodium falciparum). These results implicate evolutionary pressure by malaria selecting humans with ApoE 4/4, even considering lower survival in late life. These selective advantages may be relevant in the exploration of possible disparities between Black and Whites in the incidence of Alzheimer's Disease. PMID- 24241264 TI - HIV/AIDS in the Puerto Rican elderly: immunological changes between gender and body mass index. AB - PURPOSE: Human immunodeficiency virus (HIV) in the elderly population has serious repercussions. The elderly are underdiagnosed for HIV and the costs associated with their late-stage care represent a financial burden to the public health system. The purpose is to analyze various profiles among a cohort of elderly patients with HIV/AIDS. METHODS: This is a baseline cohort 60 years or older seen in the Retrovirus Research Center between January 2000 to December 2011. We present the profiles of our cohort stratified by gender and body mass index viewed as a covariate of interest. RESULTS: A total of 266 people (68% males and 32% females) seen at the Center were older than 60 years of age. Males were significantly more often overweight (p<.05). Females were significantly more underweight with chronic conditions (p<.05). Women had higher CD4 count and lower HIV viral loads (p<.05). Underweight elderly males were more heavily affected with the burden of HIV infection compared with women. PMID- 24241263 TI - Prevalence and correlates of depressive symptoms and resiliency among African American women in a community-based primary health care center. AB - The purpose of this cross-sectional pilot study was to determine the prevalence and correlates of depressive symptoms and resiliency among 290 African American women (AAW) in a community-based primary health care center. Descriptive statistics, Pearson product-moment correlation, and logistic regression analyses were conducted. Findings indicate that depressive symptoms are experienced by 49% of the participants, while 10% indicated a history of suicidal ideation. Participants had moderately high resiliency scores that had a statistically significant inverse relationship with depressive symptoms. This suggests that resiliency is potentially a protective factor for depressive symptoms. Depressive symptoms were positively correlated with participants' diagnosis of at least one chronic disease. The strongest predictors of depressive symptoms were previous diagnoses of a mental health condition and unemployment. This study identifies risk and potential protective factors for depression among a clinic sample of AAW. PMID- 24241265 TI - Health empowerment technologies (HET): building a web-based tool to empower older African American patient-doctor relationships. AB - Responding to health and digital inequities among older African Americans, a customized web-based mobile health information intervention is being developed for this vulnerable group and their doctors as part of the Health Empowerment Technologies (HET) Project. The belief is an empowered patient-doctor relationship leads to more improved health outcomes than patient empowerment alone. Using health information technology to empower both older African Americans and their doctors by increasing health literacy and computer capacities of both is the major HET study aim. A focus group of older African American patients and one of their doctors yielded data to help build the HET. Thematic analysis of opinions and preferences about the content and structure of the HET revealed concordance and asymmetry among the patients and doctors. While challenges prevail in its construction, building this ethnicity-specific web based health information technology presents the opportunity to integrate health information technology in clinical encounters for every patient. PMID- 24241266 TI - Acrolein-induced oxidative stress in NAD(P)H Oxidase Subunit gp91phox knock-out mice and its modulation of NFkappaB and CD36. AB - An essential component of NAD(P)H, gp91phox, maintains the functionality of the enzyme in producing oxygen radicals. NAD(P)H oxidase plays an important role in oxidative stress but its precise contribution in acrolein-induced toxicity was not explored. We examined the involvement of NAD(P)H oxidase and other oxidant system in acrolein toxicity using gp91phox knockout mice. Male gp91phox knockout (KO) mice (20-25 gm) or wild type (WT) controls were treated with acrolein (0.5 MUg/kg; 1 week). Animals were sacrificed and the liver was used to determine biochemical parameters. Knockout mice generated low (1.43 +/-.02 pg/MUg protein) free radicals as evident in 8-Isoprostane compared with the WT mice (2.19 +/- 0.1). Acrolein increased 8-Isoprostane in WT (P<.05) and KO (p<.05) mice. Xanthine Oxidase (XO) activity was higher (p<.05) in KO (0.56 +/- 0.06 MU unit/MUg protein) than WT mice. Acrolein increased XO in KO mice, but significantly increased it only in WT. Cycloxygenase (COX) activity was not different between WT and KO mice, although acroelin increased COX in WT. Knockout mice exhibited a significantly low (2.1 +/- 0.2 MUmol/mg protein) total antioxidant status (TAS) compared with the WT (3.5 +/- 0.3). Acrolein reduced TAS in both WT and KO mice equally. Baseline NFkappaB was significantly higher in KO mice, although acrolein increased NFkappaB in WT but not in KO. CD36 was higher (p<.05) in KO mice than the WT and acrolein increased (p<.05) CD36 further in KO but not in WT mice. These data suggest that NAD(P)H oxidase contributes significantly in acrolein-induced oxidative stress. We also suggests that in the absence of NAD(P)H oxidase XO plays a definitive role together with reduced antioxidant ability to compound the toxic effects of acrolein. We propose that in absence of NAD(P)H oxidase a different signaling process may involve that utilizes CD36 besides NFkappaB. PMID- 24241267 TI - Factors associated with time-to-treatment of prostate cancer in Florida. PMID- 24241268 TI - Sickle cell anemia: the impact of discovery, politics, and business. AB - Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that our novel formulation lowered the dosage requirements by 50%-75%, allowed for less frequent and shorter treatment durations, eliminating the need for a pump and the standard multi-night administration of DFO. In an iron-overloaded rat model, LDFO reduced iron in the liver, and also improved cardiac function. The lower dosage and improved safety profile makes our novel LDFO delivery system a highly desirable new therapy. Meanwhile, this system will also provide an ideal model for studying the mechanism of Fe overload-induced arrhythmias. The political and economic factors related to health care disparities are also discussed. PMID- 24241269 TI - Eliminating health disparities in women's health in Puerto Rico. AB - INTRODUCTION: Hispanic women in Puerto Rico share health concerns that affect women generally, and suffer disproportionately from some health concerns relative to non-Hispanic women. The University of Puerto Rico Women's Health Center contributes to the promotion of women's health by developing sustainable preventive services, designing programs according to women's needs, and creating awareness of sex/gender differences in health and disease. INITIATIVES: A longitudinal breast cancer early detection clinic was developed and a community screening campaign was coordinated. Focus groups were conducted. A course on sex/gender considerations in research was developed and offered. OUTCOMES: Access to early detection of breast cancer was provided through an annual on-campus clinic and a community screening campaign. A breast cancer support group resulted from focus group recommendations. Health professionals from diverse disciplines participated in a course on sex/gender considerations in research. CONCLUSIONS: Synergistic efforts towards eliminating disparities in women's health from an academic perspective provide a valuable tool for the promotion of health among Hispanic women living in Puerto Rico. PMID- 24241270 TI - Translating science into better health: the power of diversity and multicultural engagement. Preface. PMID- 24241271 TI - Translating science into better health: the power of diversity and multicultural engagement. Guest editors' message. PMID- 24241272 TI - The school-based lived experiences of adolescents with type 1 diabetes. AB - BACKGROUND: School plays a critical role in influencing the health, safety, development, and well-being of adolescents with type 1 diabetes mellitus (T1DM). However, scant research has been conducted to understand the lived experiences of these adolescents in school settings. PURPOSE: This study investigates the school based lived experiences of Taiwanese adolescents with T1DM. METHOD: A Heidegger's hermeneutic phenomenological approach was used, and 14 Taiwanese adolescents with T1DM were enrolled through purposive snowball sampling until data saturation was reached. Data were collected using audio-recorded, semistructured interviews and analyzed using the hermeneutic circle supported by qualitative analysis software NVivo 9.0. Reflective journaling, peer debriefing, memo writing, and member checking were performed to enhance the trustworthiness of the findings. RESULTS: Six interrelated themes were identified: (a) the same yet different, (b) covert and overt, (c) limitations and freedom, (d) independent and dependent, (e) derailing and being on track, and (f) disease identity and denial. Multiple factors, including disease identity, social anxiety and pressure, ignorance of school personnel and classmates, and transition to independent self-management threatened the at-school health and well-being of participants. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Much work remains to be done to adequately improve the school-life experiences of adolescents with T1DM. Interventions to facilitate their autonomy, self-efficacy, diabetes knowledge, disease identity, and handling of situational obstacles are suggested as well as improving the understanding of T1DM for teachers and classmates and facilitating more proactive care by school nurses. PMID- 24241273 TI - Establishing a model to assess the effects of school support and self-care behaviors on life satisfaction in adolescents with type 1 diabetes in Taiwan. AB - BACKGROUND: Life satisfaction is associated with positive development in adolescents. Understanding a path model of life satisfaction can help healthcare providers design interventions to improve positive development in adolescents with type 1 diabetes. PURPOSE: The aim of this study was to construct a model that assesses the effects of school support and self-care behaviors on life satisfaction in adolescents with type 1 diabetes in Taiwan. METHODS: This study used a cross-sectional design. One hundred and thirty-nine adolescents aged 10-18 years and diagnosed with type 1 diabetes were recruited. Participants completed questionnaires that assessed perceived school support, self-care behaviors, and life satisfaction. The hypothesized model was tested using structural equation modeling. RESULTS: School support significantly and directly affected self-care behaviors (beta = .46, p = .022) and life satisfaction (beta = .39, p = .034), self-care behaviors directly affected life satisfaction (beta = .56, p = .048), and school support indirectly affected life satisfaction (beta = .26, p = .015) through the mediation of self-care behaviors. The fix indices were as follows: chi2 = 8.141, df = 11, p = .701, goodness of fit index = .984, normed fit index = .949, and root mean square residual = .001. The model explained 66.1% of total life satisfaction variance. CONCLUSIONS: School support and self-care behaviors positively influence the life satisfaction of adolescents with type 1 diabetes. Improvements in school support and self-care behaviors are necessary to improve life satisfaction in this vulnerable group. PMID- 24241274 TI - Parental knowledge, concerns, and management of childhood fever in Taiwan. AB - BACKGROUND: Childhood fever is a commonly treated condition in medical settings. Many studies around the world have reported on the phenomenon of parental fever phobia. Studies of parental knowledge regarding childhood fever are lacking in Taiwan. PURPOSE: This study explores parental knowledge, concerns, and management of childhood fever and their correlates in Taiwan. METHODS: This study used a cross-sectional survey and self-administered questionnaire. Six hundred forty nine parents were recruited as participants from pediatric clinics and kindergartens in southern Taiwan. RESULTS: Nearly half (47.2%) of participants incompletely understood the healthcare information about childhood fever provided by physicians and nurses. Furthermore, 41.6% of parents were dissatisfied with the information provided. The median score of parental knowledge was 10 (interquartile range [IQR] = [8, 12] out of a maximum of 23). Parent gender, religion, education level, and occupation were independent predictors of knowledge scores. Parents who were never or sometimes concerned about childhood fever had significantly higher knowledge scores than those who were always concerned about childhood fever (median knowledge score: 11, IQR = [9, 13] vs. 10, IQR = [8, 11]). Most parents followed Western medical advice to manage childhood fever; however, 31.1% of parents combined this with traditional folk treatments. Levels of concern among parents included 86.6% of parents who frequently or always worried about their children's fever. Fever-induced anxiety was reported by 68.8% of the parents. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Participants' lack of fever-related knowledge was because, in part, of either their not understanding or their dissatisfaction with provided information. The higher level of concern compared with other countries and studies indicates that parents in Taiwan need appropriate information about fever management to alleviate their concerns and guide them in caring for their febrile children. PMID- 24241275 TI - Life-sustaining treatment: a comparison of the preferences of Taiwanese older adults and their family caregiver. AB - BACKGROUND: Written advance directives are not common practice in Taiwan; thus, when older adults are critically ill, family members are usually the ones to make decisions regarding life-sustaining treatment. PURPOSE: This study determined how well the preferences of the family members for the older adults match the preferences of the older adults themselves with regard to life-sustaining treatment. METHODS: A cross-sectional comparative descriptive research design was used in this study. Ninety-five pairs of older adults and their families were included in the final analysis. The Life Support Preferences Questionnaire was used to measure life-sustaining preferences. Paired- sample t tests were performed to compare the mean differences between the older adults' preferences and the family members' preferences for these older adults. FINDING: Family members scored higher on life-sustaining treatment preferences than the older adults for all 32 examined items, with 23 (72%) of these items showing statistical significance. CONCLUSION/IMPLICATIONS FOR PRACTICE: Communication between older adults and their family members regarding life-sustaining treatment may help prevent older adults from receiving unwanted treatments. PMID- 24241276 TI - A pilot study of an illness management and recovery program in discharged patients with schizophrenia. AB - BACKGROUND: Accumulated evidence supports the effectiveness of equipping chronically ill patients with illness management knowledge and skills. The Illness Management and Recovery (IMR) program developed by the United States government has been widely adopted for persons with mental illness. However, few studies support its effectiveness in patients with schizophrenia. PURPOSE: This pilot study developed a culturally adapted and abbreviated version of the IMR for Taiwanese patients with schizophrenia who were ready for discharge from the hospital. Furthermore, we investigated the impact of the program in terms of illness knowledge, drug attitude, insight, and psychopathology. METHODS: The original IMR was condensed and modified for implementation during participants' preparation for hospital discharge. Using a preexperimental design, pretest and posttest assessments for a single group of 26 participants received the new IMR twice a week for 3 weeks on the four outcome indicators of illness knowledge, drug attitude, insight, and psychopathology. RESULTS: Participants improved in terms of treatment-related illness knowledge, insight, and affective-domain psychopathology (p < .01) after intervention completion. Average participant attendance was 5.45 sessions out of 6 total sessions. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The intensive symptom and medication-focused IMR model for soon-to be-discharged patients with schizophrenia had positive impacts on illness management. In the future, studies using a two-group randomized controlled design and extended follow-up should be conducted to determine the long-term effects of IMR. PMID- 24241277 TI - Effectiveness of a nursing consultation intervention for older people with functional mobility impairments: a prospective, longitudinal study. AB - BACKGROUND: There is a need for prevention strategies in elderly individuals with mobility impairments. PURPOSE: The aim of this study was to determine the effects of nursing consultations on the functional abilities and quality of life of elderly individuals with mobility impairments after discharge from a rehabilitation facility. METHODS: A single-site, prospective, longitudinal study with a nonequivalent control group pretest-posttest design was conducted in a geriatric rehabilitation facility and in the living environments of the patients after discharge. The intervention consisted of nurse-delivered consulting home visits and follow-up telephone calls. Patient quality of life and functional status were the primary outcomes, and self-efficacy was the secondary outcome. Data were collected at admission, at discharge, and at a 6-month follow-up visit. RESULTS: A cohort of 124 patients participated in the study. The intervention group showed a nonsignificant improvement in functional status compared with the control group. The intervention did not affect quality of life, except for a trend toward significance in the social domain (p = .060). CONCLUSIONS: The findings of this study suggest that nursing consultations do not significantly improve functional status and have almost no effect on quality of life. PMID- 24241278 TI - Case management knowledge and preparedness among public health nurses. AB - BACKGROUND: Taiwanese public health nurses are increasingly required to act as case managers. However, little is known about nurses' knowledge and preparedness levels in assuming the responsibilities of case management. PURPOSE: This article explores the knowledge and preparedness levels of experienced public health nurses related to case management. METHODS: A cross-sectional survey of Taiwanese public health nurses was conducted. A structured questionnaire was used to collect data on participants' knowledge of case management and perceived preparedness levels in performing role activities. The questionnaire consisted of three sections: Section One featured 20 multiple-choice items, Section Two included case manager role activities, and Section Three gathered demographic information. RESULTS: One hundred seventy-eight public health nurses were recruited from 10 health offices, with a 99% valid response rate. The overall average correct response rate for case management knowledge was 49%, which fell significantly below the minimum acceptable average score of 60%. Participants held neutral opinions regarding their preparedness levels for performing case management role activities, with a mean score of 3.2 (SD = 0.5, range = 1-5). In addition, this study unexpectedly found that the higher knowledge level group was significantly younger on average than the lower knowledge group. More than three quarters (82%) of participants had no prior education in case management. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results reflect substantial gaps in Taiwanese public health nurses' knowledge and preparation for the practice of case management. There is an urgent need to strengthen case management continuing education for public health nurses and address knowledge deficits and the role activities identified with lower preparedness levels. PMID- 24241279 TI - The development of nursing workforce allocation standards for acute care general wards in Taiwan. AB - BACKGROUND: Adequate nursing workforce is critical to ensure patient safety and reduce the incidence of adverse events. PURPOSE: This study explores and compares the nursing workforce allocation situation in the acute care general wards of Taiwan's three hospital tiers and, based on findings, develops standards for adequate nursing workforce allocation and nurse-to-patient ratios in acute care general wards at each tier. METHODS: This study uses multiple research methods, including literature review, questionnaire survey, and expert focus group discussion. Final consensus is achieved using a public hearing and questionnaire survey. RESULTS: The severity of patient conditions differs among hospital tiers. Therefore, each tier requires a nursing workforce allocation standard appropriate to its situation. Study findings indicate that nurse-to-bed ratios and nursing hours are valid indicators of nursing workforce allocation needs. The results of expert discussions and public hearings recommend 0.53 nurses per bed and 2.8 nursing hours for academic medical centers, 0.49 nurses per bed and 2.6 nursing hours for metropolitan hospitals, and 0.40 nurses per bed and 2.1 nursing hours for local community hospitals for the current stage of healthcare development; 0.57 nurses per bed and 3.0 nursing hours for academic medical centers, 0.53 nurses per bed and 2.8 nursing hours for metropolitan hospitals, and 0.44 nurses per bed and 2.3 nursing hours for local community hospitals in 3 years; and 0.61 nurses per bed and 3.2 nursing hours for academic medical centers, 0.57 nurses per bed and 3.0 nursing hours for metropolitan hospitals, and 0.48 nurses per bed and 2.5 nursing hours for local community hospitals in 5 years. CONCLUSIONS: Study results may provide a basis for better allocating nursing workforce in hospitals, setting formal standards for minimum nurse-to-patient ratios, and assessing nursing workforce needs at the national level. PMID- 24241280 TI - Molecular genetic epidemiology of human diseases: from patterns to predictions. AB - Databases of disease-associated or disease-causing mutations allow the study, not only of the molecular mechanisms underlying the primary lesions at the DNA level, but also of the functional consequences of mutation at the phenotypic level. The Human Gene Mutation Database (HGMD) and the bioinformatics analyses of its content provide an illustrative example of this indirect approach to molecular genetic epidemiology. In fact, the Bayesian type of reasoning underlying previous scientific analyses of HGMD data is also reflected in current software tools used to predict the likely disease relevance of a newly detected genetic variant. After a brief resume of the past scientific utility of HGMD, we, therefore, shortly review three representative and commonly used examples of these tools, namely SIFT, PolyPhen-2 and NNSplice. PMID- 24241281 TI - MicroRNA-related sequence variations in human cancers. AB - MicroRNAs are emerging as a most promising field in basic and translational research, explaining the pathogenesis of numerous human diseases and providing excellent tools for their management. This review considers the effects of microRNA sequence variations and their implication in pathogenesis and predisposition to human cancers. Although the role of microRNAs still remains to be elucidated, functional, and populational studies indicate that microRNA variants are important factors underlying the process of carcinogenesis. Further understanding of the cellular and molecular basis of microRNA action will lead to the identification of their new target genes and microRNA-regulated pathways. As a consequence, novel models of cancer pathogenesis can be proposed, and serve as a basis for elucidation of new prognostic and diagnostic tools for human cancers. PMID- 24241282 TI - Orai1-dependent calcium entry promotes skeletal muscle growth and limits fatigue. AB - Store-operated Ca2+ entry (SOCE) in skeletal muscle involves signalling between stromal-interacting molecule 1 (STIM1) in the sarcoplasmic reticulum (SR) and Ca2+ selective Orai1 channels in the sarcolemma. Here we generate transgenic mice with muscle-specific expression of dominant-negative Orai1 (dnOrai1) and demonstrate that Orai1-dependent SOCE promotes growth and limits fatigue in adult skeletal muscle. dnOrai1 mice lack SOCE specifically in muscle but are fertile and thrive well into adulthood. Although muscle ultrastructure, excitation contraction (EC) coupling, fibre type, and expression of other Ca2+ regulatory proteins are unaltered, dnOrai1 mice exhibit reduced body weight, muscle mass and fibre cross-sectional area. Importantly, during intense repetitive activity, dnOrai1 mice display increased susceptibility to fatigue at the single fibre, excised muscle and whole-animal levels. We further show that STIM1 and Orai1 proteins co-localize within the triad junction but do not exist in a preassembled context. These results show that Orai1-dependent SOCE has an important physiological role in muscles of adult mice. PMID- 24241283 TI - Symptotic detection of chimerism: Y does it matter? AB - Microchimerism (MC), transplacental acquisition of allogeneic cells from the mother (maternofetal MC) or from the fetus (fetomaternal MC) has been in the focus of research recently. Amplicons using Y-chromosome specific SRY and DYS14 sequences have been used as markers to trace cells from a male fetus in the mother. The sensitivity of these markers in formaldehyde fixed paraffin embedded samples, however, is less than optimal. To study chimerism in breast cancer we took advantage of the evolutionary history of the Y chromosome and designed amplicons on gene repeats to generate additive PCR signals. The increased sensitivity detected high incidence of male chimerism in normal breast tissues. We also showed correlation with protection from cancer with unique quantitative biology. Accumulating data from biology and medicine indicate that natural chimerism is astonishingly frequent and may affect human conditions. We hypothesize that it has significant evolutionary ramifications as well. PMID- 24241284 TI - Individual selection, culture and manipulation of higher plant cells. AB - Due to the heterogeneity in morphology, physiological and morphogenetical capabilities of higher plant cells in mass culture, the development of methods for individually culturing defined cells seemed to be useful and necessary. Individual cell culture represents a powerful tool for studies on the physiology of different cell types, the analysis of differentiation programs, the genetic manipulation of plant cells and cell-cell interactions. An improved microculture system based on a computer-controlled set-up for the efficient selection, transfer and individual culture of defined higher plant cells until regeneration of whole plants is described. Related experimental approaches for individually manipulating higher plant cells under controlled conditions, such as electrofusion of defined pairs of protoplasts and subprotoplasts, cell reconstruction and intranuclear microinjection of protoplasts and karyoplasts - mainly performed with cells of the crop plant Brassica napus L. - are presented. PMID- 24241285 TI - True potato seed quality. AB - Environmental influence on physiological factors that determine seed quality is discussed in relation to true potato seed (TPS). This review has been motivated by the need for high quality seed for the proper evaluation of TPS technology. The objectives of tuber production may not be in harmony with those required for the production of high quality TPS. The production of high quality TPS may be influenced by the stronger sink strength ability of fast developing tubers for assimilation of available nutrients. Earliness of tuber formation, which is needed in TPS progenitors, may tend to result in incomplete TPS development. Limiting conditions during seed development decrease the potential of the seed for field establishment. Seed vigor is the most important attribute of seed quality since it is essential for seedling performance under the adverse conditions commonly encountered during field development. The attractiveness of TPS technology for tropical areas, where potato production is limited by low quality seed tuber availability, is decreased by the lack of seedling vigor and uniformity of seedlings derived from TPS. Current research indicates that considerable genetic improvement of TPS vigor and uniformity is possible. It is suggested that significant immediate improvement of TPS quality would result from agronomic techniques that reflect understanding of the physiological factors that influence the production and maintenance of high quality seed. Research areas needed to develop methodologies for TPS production with optimum expression of genotype are identified. PMID- 24241286 TI - Formation of callus and somatic embryos from protoplasts of a commercial hybrid of maize (Zea mays L.). AB - Protoplasts isolated from a totipotent embryogenic cell suspension culture of Zea mays L. (cultivar 'Dekalb XL82') underwent sustained cell divisions when cultured in liquid as well as agarose media. Optimal colony formation (5%) occurred in a liquid medium containing 0.5 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D). A soft and unorganized callus was formed when the protocolonies were transferred to agar solidified suspension maintenance medium. Compact, organized and yellow to pale green folded structures and somatic embryos were formed upon subsequent transfer of this callus to a low 2,4-D medium. Clusters of somatic embryos germinated precociously but no plants were recovered. PMID- 24241287 TI - Mating system and multilocus associations in a natural population of Pseudotsuga menziesii (Mirb.) Franco. AB - Arrays of open-pollinated seeds were assayed for allozyme polymorphisms at ten loci (Aat2, Est1, G6pd, Idh, Mdh2, Mdh3, Pgm, Sod, 6Pgd1, 6Pgd2) to obtain estimates of the outcrossing rate and assess multilocus association in a natural population of coastal Douglas-fir, Pseudotsuga menziesii (Mirb.) Franco. The allele frequencies in the samples of adult trees and pollen-gamete pool were similar. Maximum-likelihood estimators of the outcrossing rate for individual loci and two multilocus models were derived using counting methods. The single locus maximum likelihood estimates (MLEs) of the outcrossing rate were significantly heterogeneous; they varied over a more than two-fold range from 0.404 to 0.935, with an average MLE of 0.741. Both multilocus MLEs of the outcrossing rate were 0.887. The sample of trees was in random mating equilibrium when assessed on a pairwise-locus basis using Burrows' composite measure of gametic disequilibrium, with one exception (Mdh2 Sod) that was attributable to a rare "gametic" class. In the sample of pollen gametes, 5 of the 45 pairwise-locus associations were nominally significant at the 0.05 level: Idh Est1, Mdh2 Sod, Aat2 Est1, Aat2 Mdh3, and Est1 Mdh3. These apparent associations were attributable in most cases to the relative excess of uncommon or rare paternal gametes of discernibly outcrossed embryos. An additional two-locus association was identified for Mdh2 Pgm which was marginally significant for the major partition of the contingency table that excluded paternal gametes with the rare allele Mdh2 (2) . PMID- 24241289 TI - Ancestral covariance and the Bulmer effect. AB - An n-generation pedigree is set up and selection is carried out generation by generation. The influence of this procedure on the covariances in subsequent generations is assessed and, ultimately, Bulmer's general recursion formula for the reduction in genetic variance due to selection is obtained. The results are extended to assess the effect of selection of one or more characters on the genetic covariance matrix of a number of characters. The concept of ancestral regression is also used to provide a different insight into the selection process and to justify some models used in the analysis of assortative mating. PMID- 24241288 TI - The combination of polima cms and cytoplasmic triazine resistance in Brassica napus. AB - Protoplast fusion was used to combine cytoplasmic triazine resistance (ctr) and Polima type cytoplasmic male sterility (cms) in Brassica napus. The cybrids produced constitute the major biological input required for the production of commercial single-cross hybrid rapeseed bearing cytoplasmic triazine resistance. The results also indicate that Polima cms is associated with the mitochondrial genome. PMID- 24241290 TI - Chondriome analysis in sexual progenies of Nicotiana cybrids. AB - We studied the chondriomes (the mitochondrial genomes) of sexual-progeny plants derived from eleven Nicotiana cybrids which resulted from donor-recipient protoplast fusions. The recipients were either N. tabacum or N. sylvestris and the donor (of the cytoplasm) was N. bigelovii. The chondriomes were characterized by the mitochondrial DNA (mtDNA) restriction-patterns. The differences in mtDNA restriction patterns were revealed after Sal I digestions and probing the respective Southern-blots with three mtDNA fragments. The hybridization patterns of mtDNAs from 35 second-generation plants (i.e. the sexual progeny derived from the cybrid plants) indicated only minor variations between plants derived from the same cybrid but pronounced variations among sibs derived from different cybrids. The mtDNA of 32 second-generation plants varied from both original fusion partners but the mtDNA of one (male-sterile) plant was apparently identical with the mtDNA of one of the original donor (N. bigelovii) and the mtDNA of two other (male-fertile) plants was apparently identical to the mtDNA of an original recipient (N. sylvestris). Generally, the mtDNAs of male-fertile, second-generation plants were similar to the mtDNAs of the original recipients while the mtDNAs of the male-sterile second-generation plants were similar to the mtDNA of the donor (N. begelovii). The analyses of mtDNAs from the thirdgeneration plants indicated stabilization of the chondriomes; no variations were detected between the mtDNAs of plants derived from a given second-generation plant. PMID- 24241291 TI - Nor loci analysis in progenies of plants regenerated from the scutellar callus of bread-wheat : A molecular approach to evaluate somaclonal variation. AB - Progenies of plants regenerated from scutellar callus of bread wheat (Triticum aestivum L.) were analysed for the organization of the intergenic spacer of the rRNA genes, located at the sites of the nucleolar organizer region (Nor loci). Sexual progenies derived from the regenerated plants of three wheat cultivars were subjected to this analysis. The respective DNAs were digested with the restriction endonuclease TaqI, and probed with a specific rDNA fragment by Southern blothybridization. The intergenic rDNA spacer could thus be characterized for each of the three cultivars. Thirty-eight progeny plants of the cultivars 'Chinese Spring' and 'Miriam' were found to be stable in their organisation of the Nor loci: no changes relative to the Nor of control plants from these cultivars were revealed. On the other hand, three progeny plants of 'ND7532' showed reduction in the number of the rDNA spacers. Since no variability in the Nor loci could be revealed among control 'ND7532' plants, this seems to indicate that the changes in the progeny of regenerated plants resulted from the in vitro culture of the scutellar callus. Grain glutenin and gliadin profiles of sexual progenyplants derived from scutellar calli of 'Chinese Spring', of 'Miriam' as well as of 'ND7532' were identical to the respective control plants of these cultivars, indicating low (or no) somaclonal variation in these grain proteins in the analyzed plants. PMID- 24241292 TI - Nucleolus organizer regions and heterochromatin in the zebu (Bos indicus L.). AB - Ag-NOR staining and a counterstain enhanced fluorescence technique (chromomycin A3/distamycin A/DAPI-staining = CDD-method) and G-banding, respectively, have been applied to the zebu (Bos indicus L.) chromosomes. The nucleolus organizer regions (NORs) were found in the telomeric regions of chromosomes nos. 2, 3, 4, 11, and 28. CDD staining led to a well-defined R-banding pattern along the chromosome arms and to the visualization of centric heterochromatic bands of variable sizes. PMID- 24241293 TI - Chromosomal location of isozyme and seed storage protein genes in Dasypyrum villosum (L.) Candargy. AB - The zymogram phenotypes of glucose-phosphate isomerase (GPI), alcohol dehydrogenase-1 (ADH-1), glutamate oxaloacetate transaminase (GOT), superoxide dismutase (SOD), lipoxygenase (LPX), esterase (EST) and the banding patterns of gliadin and glutenin seed storage proteins were determined for Triticum aestivum cv. 'Chinese Spring' (CS), Dasypyrum villosum, the octoploid amphiploid T. aestivum cv. 'Chinese Spring' D. villosum (CS * v) (2n=8x=56; AABBDDVV), and for five CS-D. villosum disomic addition lines. The genes Gpi-V1, Adh-V1, Got-V2, and Sod-V2 coding for GPI-1, ADH-1, GOT-2, and SOD-2 isozymes were located in D. villosum on chromosome 1V, 4V, 6V, and 7V, respectively. Genes coding for gliadin and glutenin-like subunits are located in D. villosum chromosomes 1V. There are no direct evidence for chromosomal location of genes coding for GOT-3, EST-1 and LPX-2 isozymes. The linkage between genes coding for glutenin-like proteins and GPI-1 isozymes in chromosome 1V is evidence of homoeology between chromosome 1V and the chromosomes of homoeologous group 1 in wheat. PMID- 24241294 TI - Genetics of resistance to Puccinia graminis tritici in 'Chris' and 'W3746' wheats. AB - 'Chris' wheat possessed genes Sr5, Sr7a, Sr8a, Sr9g and Sr12. 'W3746', derived from the cross 'Chris'/'Baart', possessed Sr7a and Sr12. The response conferred by Sr7a was influenced by the genetic background. Although Sr7a or Sr12 alone conferred no observable resistance upon adult plants, the adult resistances of 'Chris' and 'W3746' to predominant pathotypes appeared to be associated with the interaction of Sr7a and Sr12, or genes at closely linked loci. PMID- 24241295 TI - Nuclear DNA regulates the level of ribulose 1,5-bisphosphate carboxylase oxygenase in Medicago sativa L. AB - The response to selection for leaf proteins was studied during three selection cycles. Selection for high total nitrogen content showed 75% heritability, and the levels of both ribulose 1,5-bisphosphate carboxylase oxygenase (Rubisco) and cytoplasmic protein were strongly under nuclear DNA control. High and low protein content were correlated with chloroplast area. Although the amounts of nuclear DNA were similar, the ratio of Rubisco/DNA and chlorophyll/DNA changed during the selection process. It can be concluded that the levels of Rubisco achieved in mature plants of M. sativa are under nuclear DNA control. The possible involvement of small subunit (SSU) genes in controlling these levels is discussed. PMID- 24241296 TI - Anther culture of maize and the visualization of embryogenic microspores by fluorescent microscopy. AB - Three maize genotypes previously shown in the literature to respond to anther culture were tested under various conditions. Studies indicated that embryogenic response ranged from 0 to 100 embryos per 1,000 anthers plated and was significantly lower without cold pretreatment of the anthers. Culture in liquid media tended to produce more embryos than in semi-solid as did the addition of activated charcoal to either liquid or solid culture media. Most results were confounded by plant-to-plant variation which tended to obscure significant differences. In one study, germination rate of androgenetic embryos averaged about 20%, but only 26% of those embryos that germinated completed their reproductive cycle and formed seed albeit through sibpollination since plants could not be selfed. Chromosome counts using root tip squashes indicated that regenerated plants were either haploid or diploid but plants scored as non diploid yielded as much seed as scored diploids. This suggests that progeny can be recovered even from putative haploids, presumably as a result of "sectoring" in the developing ear. A DNA-specific fluorescent dye was used to visualize the presence of putative embryogenic microspores (PEMs) during the culture period. PEM counts were a function of time in culture and were apparently greater than the number of embryos obtained for a given treatment. The data indicate that, as previously reported for other species, both induction and survival phases also exist in maize anther culture. PMID- 24241297 TI - Genetic evaluation of traits distributed as Poisson-binomial with reference to reproductive characters. AB - A procedure of genetic evaluation of reproductive traits such as litter size and survival in a polytocous species under the assumption of polygenic inheritance is described. Conditional distributions of these traits are assumed to be Poisson and Bernoulli, respectively. Using the concept of generalized linear models, logarithmic (litter size) and probit (survival) functions are described as linear combinations of "nuisance" environmental effects and of transmitting abilities of sires or individual breeding values. The liability of survival is expressed conditionally to the logarithm of litter size. Inferences on location parameters are based on the mode of their joint posterior density assuming a prior multivariate normal distribution. A method of estimation of the dispersion parameters is also presented. The use of a "truncated" Poisson distribution is suggested to account for missing records on litter size. PMID- 24241298 TI - Elimination of Solanum phureja nucleolar chromosomes in S. tuberosum + S. phureja somatic hybrids. AB - The karyotype of the dihaploid SVP1 line of S. tuberosum (2n=2x=24) showed two nucleolar chromosomes with differently sized satellites. The diploid SVP5 line (2n=2x=24) and tetraploid regenerants of S. phureja had larger but similar satellites. Somatic hybrids between the diploid lines of these potato species with genome combinations 4 tub + 2 ph (plants 1-3), 2 tub + 4 ph (plants 4-7) and 4 tub + 4 ph (plant 8) had lost 2 phureja nucleolar chromosomes if 4 phureja genomes were present. One phureja nucleolar chromosome of plants 1-3 and both of plants 5 and 7 had rearranged satellites. Elimination of the two nucleolar chromosomes occurred preferentially, was under genetic control, and probably took place during early callus development. NOR activity resulting in rear-rangements between NORs may have caused the elimination. PMID- 24241299 TI - Genetic mapping of an ancient translocation in the genus Lens. AB - Segregation of 18 marker genes was monitored in selfed progeny of a Lens culinaris * L. ervoides hybrid; five linkage groups were mapped, one of which contained a reciprocal translocation break-point that differentiates between the parents. Four markers were found to be linked to the translocation break-point: Aco-1 and Pgm-2 on one side and Gs and Got-2 on the other. The gene pairs on both sides of the translocation are not linked in L. culinaris or in L. orientalis. The L. ervoides gene order was also found in L. odemensis but with significantly reduced map distances. Analysis of monogenic segregations in a number of Lens inter-specific crosses revealed some consistent patterns of deviations from the expected Mendelian ratios. The factors responsible for these unequal segregations, genotypic effects on recombination frequencies, negative interference, and the possible ancient origin of the translocation are discussed. PMID- 24241300 TI - Analysis of meiosis in triticale (XTriticosecale Wittmack) X rye (Secale cereale L.) F1 hybrids at three ploidy levels. AB - Triticales (XTriticosecale Wittmack) at three ploidy levels (8x, 6x, 4x, x=7) were crossed with diploid rye (Secale cereale L.) to produce a solitary hypopentaploid hybrid (2n=32), and a number of tetraploid (2n=4x=28) and triploid (2n=3x=21) hybrids. The hybrids exhibited a morphology which was intermediate between the parents. The number of bivalents ranged from 1-7 (4.65 per cell) in hypopentaploid, from 2-12 (7.13 per cell) in tetraploid and from 4-9 (6.84 per cell) in triploid hybrids. In 4x and 3x hybrids, trivalents and quadrivalents were also observed at low frequencies (range 0-1; mean 0.01-0.03 per cell). Chiasmata frequency was highest in triploid hybrids (12.44 per cell), lowest in hypopentaploid (5.37 per cell) and intermediate in tetraploids (10.54 per cell). More than 7(11) were found in 39.7% pollen mother cells (PMC's) in the 4x hybrids and in 5.0% PMCs in 3x hybrids. It is concluded that an increase in the relative proportion of wheat chromosomes in the hybrids had a slight suppression effect on homologous as well as homoeologous pairing of rye chromosomes. Contrary to this, the relative increase in rye complement promoted homoeologous pairing between wheat chromosomes. In triploid hybrids, the chiasmata frequency as well as the 'c' value were the highest, suggesting that in tetraploid hybrids rye chromosomes had a reduced pairing (low frequency of ring bivalents). PMID- 24241301 TI - Effect of genome combinations on stability of yield and yield components in wheats and triticales. AB - The data on number of grains/spike, 100 grain weight and grain yield/plant in eighteen genotypes of four genome combinations (AABB- 4 genotypes, AABBDD- 6 genotypes, AABBRR- 5 genotypes and AABBDDRR- 3 genotypes) were recorded for eight environments created by combining two dates of sowing, two fertilizer regimes and two spacings. Two stability parameters-regression coefficient (b) and deviation from regression (Sd (2)) were computed. Joint regression analyses revealed that the genotypes differed significantly for these characters. A significant variation due to environments was also found. A comparative study of performance of genotypes belonging to four genome combinations revealed that the genes for stability are not uniformly distributed in these genome combinations. Stability may largely depend on gene combination rather than on genome combination. PMID- 24241302 TI - Genetic analysis of ecological relevant morphological variability in Plantago lanceolata L. : 2. Localisation and organisation of quantitative trait loci. AB - Morphological variability was analysed in an F2-generation derived from crosses between two ecotypes of Plantago lanceolata L. Six allozyme loci, localised in five linkage groups, were used as markers. For two marker loci, Got-2 and Gpi-1, segregations did not fit monogenic ratios. In the linkage groups to which these two loci belonged, male sterility genes appeared to be present. In these crosses, male sterility (type 3, as described by Van Damme 1983) may be determined by two recessive loci located in the linkage groups of Got-2 and of Gpi-1. Many correlations of morphological and life history characters with allozyme markers were observed. The quantitative trait loci did not appear to be concentrated in major gene complexes. Often many loci were involved, sometimes with effects opposite to those expected from the population values. Main effects of the linkage groups appeared to be more important than interaction effects in determining variability. It also appeared that there is a positive correlation between the number of heterozygous allozyme loci and generative growth. PMID- 24241303 TI - Changes in frequencies of variegated leaves in NMU treated tobacco : Evidence for a differential response to NMU. AB - Seeds of Nicotiana tabacum were allowed to imbibe water for 1 h and were then treated with 5-20 mM N-nitroso-N-methylurea (NMU) for 1 h. Seedlings were planted out separately and leaves no. 1-6 were scored individually after expansion was complete: frequencies of leaves with mutant sectors and the percentage of leaf area that was mutant were determined for the numbered leaves. Treatment with 5 mM NMU gave few mutant plants but after 10-20 mM NMU 50-98% of plants were mutant. The frequency of mutant leaves increased from leaf no. 1 to leaves no. 3-4; as much as a 5.6-fold increase, from leaf no. 1 to no. 3 was found. There appears to be differential sensitivity to NMU: it is lower in the initial cells for leaf no. 1 than in the initials for leaves no. 3 or 4. Leaves no. 1-4 arise from four different groups of initial cells: mutations appearing in two or more of leaves no. 1-4 must, therefore, arise independently of one another. From mutants found in leaves no. 1-4 it is estimated that the mean number of mutations per seedling was 2.68 after treatment with 20 mM NMU. Mean percentage of leaf surface area occupied by mutant sectors increased from 14% to 29.4% as NMU concentration increased from 10 to 20 mM. It also increased significantly from leaf no. 1 to leaves no. 3-6 after treatment with 15 or 20 mM NMU but not after 10 mM NMU: this suggests that mutagen treatment may affect the formation of mutant homoplasmon cells and their contribution to leaf primordia. PMID- 24241304 TI - In vitro induction of haploid plants from unpollinated ovules and ovaries of the sugarbeet (Beta vulgaris L.). AB - Haploid plantlets from male fertile and male sterile sugarbeet plants could be induced at frequencies up to 2.2% using ovule culture. Ovary culture on media without charcoal resulted in a similar induction frequency. Plant development was inhibited by callus development originating from the mother tissue. When the callus parts were removed and the ovule transferred to a new medium without 2,4 D, callus formation could be inhibited by adding 0.5% charcoal to the medium. Up to 6.1% haploids were induced. Chromosome counts in leaf tips, chloroplast counts and isozyme patterns revealed that all plants were haploid and originated from the haploid cells of the embryo sac. Root tips showed spontaneous polyploidisation. PMID- 24241305 TI - Growth and body composition changes in mice selected for high post-weaning weight gain on two levels of feeding. AB - Two lines of mice were selected for high post-weaning weight gain (3 to 6 weeks) adjusted for 3 week weight. One line (F) was grown on freely available food and the other (S) on a feeding scale set at the same level for all mice. Food intake of the S line averaged 80% of the F line. The realised heritabilities after 6 generations of selection were 0.38+/-0.06 and 0.33+/-0.07 for the F and S lines, respectively. In generation 7, mice from the F and S lines and from an unselected control line (C) were compared on both free and set levels of feeding from 3 weeks to 9 weeks of age. Measurements taken were growth rate, appetite, food conversion efficiency (weight gain/food intake) and body composition (fat, protein, ash, water). The F and S lines grew more rapidly and efficiently than the C line on both levels of feeding, each line performing best on the level of feeding on which it was selected. The average genetic correlation between growth rates of the same line on the two feeding levels was 0.54+/-0.10. The F line grew 19% faster and was 9% more efficient than the S line on free feeding but the S line grew 15% faster and was 15% more efficient than the F line on set feeding. Relative to the C line, food intake per day on free feeding was 4% higher in the F line and 6% lower in the S line. There was no difference between the lines in food intake/g body weight. The rate of deposition of all body components increased in both selection lines. In the F, S and C lines respectively, efficiencies of gains in body components (10(2)x gain/food) were 1.79, 1.31 and 1.06 for fat, 1.53, 1.63 and 1.22 for protein and 5.88, 6.45 and 4.98 for protein + water. Apparently energy lost as heat was reduced in both the F and S lines. The partitioning of energy retained was altered in favour of more fat in the F line and more protein in the S line. PMID- 24241306 TI - The membranes of slowly drought-stressed wheat seedlings: a freeze-fracture study. AB - Seedlings of Triticum aestivum L. cv. Neepawa were slowly drought-stressed by witholding water after sowing in pots. Leaf extension stopped during development of the third leaf. Damage was assessed by rewatering the pots and measuring regrowth; 1-5 d after growth stopped, rewatering induced significant regrowth within several hours; 6-13 d after growth stopped, regrowth was delayed; from 14 d after growth stopped, no regrowth occurred after rewatering. Leaf bases were excised from the drought-stressed seedlings during this period of increasing damage, and were freeze-etched.Intramembranous particles (IMP) were evenly scattered in the plasma membrane in those plants which regrew immediately after rewatering. In the plants which regrew after a delay or which did not regrow on rewatering, there were patches without IMP in plasma membrane, nuclear envelope, and other membranes. Plasma membrane, nuclear envelope and possibly other membranes were sometimes partly replaced by vesicles, possibly formed from the original membrane. Such vesiculation occurred in a few cells in plants which survived the stress with a delayed regrowth, and was commoner in the plants which did not recover. The results support the idea that slow drought induces IMP-free patches in membranes including the plasma membrane, this induces membrane reorganisation including vesiculation of membranes and coagulation of protoplasm, and that these are expressed as delayed or failed regrowth. Some IMP-free patches in the plasma membrane had a faint ordered sub-structure, possibly a hexagonal lipid phase. Such patches were infrequent and IMP sometimes occurred in areas of plasma membrane having an apparently similar sub-structure. Thus the IMP-free patches could not be explained by a lamellar-hexagonal phase transition. As the stress became damaging, vesicles and endoplasmic reticulum accumulated immediately next to the plasma membrane. Mainly during the early period of damaging stress (6-10 d after growth stopped), depressions, invaginations, and rarer "lesions" occurred in the plasma membrane, sometimes associated with some of the IMP-free patches. In the same period, many nuclear envelopes had exceptionally large nuclear pores. PMID- 24241307 TI - The extrafloral nectaries of cowpea (Vigna unguiculata (L.) Walp): I. Morphology, anatomy and fine structure. AB - The cowpea bears two distinctive types of extrafloral nectaries. One, on the stipels of trifoliolate leaves, consists of a loosely demarcated abaxial area (1 2 mm diameter) of widely-spaced trichomes (papillae) borne on a stomata-free epidermis, and lacking a specific vascular supply. Each trichome has up to eight apical (head) cells, two to four intermediate cells, and a single large stalk cell. The secretory faces of the apical cells bear wall ingrowths and an easily detached cuticle. The wall separating the stalk cell and the underlying epidermal cell(s) has a mean plamodesmatal frequency of 25/MUm(2). The second type of nectary consists of a large elliptical mound of tissue (short and long axes about 2 mm and 4 mm) formed between a pair of flowers on an inflorescence stalk. It comprises four to eight cone-shaped subnits of secretory tissue, each with a circular secretory orifice and an individual supply of phloem, but not of xylem. Cells of the secretory tissue of the nectary subunits separate as they mature, and nectar flows to the orifice through the resulting intercellular spaces. Intact secretory cells and cellular debris are extruded into the nectar. Some of the sieve elements terminating in the inner secretory tissue exhibit open sieve pores. Each mature secretory cell contains many small (2 MUm diameter) spherical protein bodies and one to three large (up to 2-3 MUm diameter 15 MUm long), paracrystalline bodies. These inclusions are absent or not fully developed in inner, less mature regions of the secretory tissue. Mechanisms of secretion are proposed for the two classes of nectary, including estimates of flux of sugar into the trichomes of the stipel nectary. PMID- 24241308 TI - The extrafloral nectaries of cowpea (Vigna unguiculata (L.) Walp.) II. Nectar composition, origin of nectar solutes, and nectary functioning. AB - Nectar was collected from the extrafloral nectaries of leaf stipels and inflorescence stalks, and phloem sap from cryopunctured fruits of cowpea plants. Daily sugar losses as nectar were equivalent to only 0.1-2% of the plant's current net photosynthate, and were maximal in the fourth week after anthesis. Sucrose:glucose:fructose weight ratios of nectar varied from 1.5:1:1 to 0.5:1:1, whereas over 95% of phloem-sap sugar was sucrose. [(14)C]Sucrose fed to leaves was translocated as such to nectaries, where it was partly inverted to [(14)C]glucose and [(14)C]fructose prior to or during nectar secretion. Invertase (EC 3.2.1.26) activity was demonstrated for inflorescence-stalk nectar but not stipel nectar. The nectar invertase was largely associated with secretory cells that are extruded into the nectar during nectary functioning, and was active only after osmotic disruption of these cells upon dilution of the nectar. The nectar invertase functioned optimally (phloem-sap sucrose as substrate) at pH 5.5, with a starting sucrose concentration of 15% (w/v). Stipel nectar was much lower in amino compounds relative to sugars (0.08-0.17 mg g(-1) total sugar) than inflorescence nectar (22-30 mg g(-1)) or phloem sap (81-162 mg g(-1)). The two classes of nectar and phloem sap also differed noticeably in their complements of organic acids. Xylem feeding to leaves of a range of (14)C-labelled nitrogenous solutes resulted in these substrates and their metabolic products appearing in fruit-phloem sap and adjacent inflorescence-stalk nectar. (14)C-labelled asparagine, valine and histidine transferred freely into phloem and appeared still largely as such in nectar. (14)C-labelled glycine, serine, arginine and aspartic acid showed limited direct access to phloem and nectar, although labelled metabolic products were transferred and secreted. The ureide allantoin was present in phloem, but absent from both types of nectar. Models of nectary functioning are proposed. PMID- 24241309 TI - Protein bodies from the cotyledons of Cytisus scoparius L. (Link). Ultrastructure, isolation, and subunit composition of albumin, legumin and vicilin. AB - The structure of protein bodies differs in the upper and lower parts of the cotyledons of mature seeds of Cytisus scoparius L. The palisade-mesophyll cells contain essentially homogeneous protein bodies, without globoids, but the protein bodies of the spongy-mesophyll cells are heterogeneous, with numerous globoids. Albumins, legumins and vicilins were selectively extracted from isolated protein bodies and their subunits separated by SDS-PAGE, under non-reducing and reducing conditions. PMID- 24241310 TI - Changes in ultrastructure of plasmodesmata during spermatogenesis in Chara vulgaris L. AB - Two types of plasmodesmata are found within an antheridium of Chara vulgaris: open plasmodesmata filled with electron-transparent cytoplasm, and plugged plasmodesmata, filled with an osmiophilic dense substance. Open plasmodesmata occur only between cells synchronized completely in respect of their advancement in cell-cycle progression or differentiation. Plugged plasmodesmata connect different types of cells or cells of the same type at various stages of the cell cycle. Open plasmodesmata may become plugged, and vice versa. These changes are connected with the limitation or extension of synchronization of cellular divisions and differentiation within the groups of cells in the antheridium. PMID- 24241311 TI - Biosynthesis of pentacyclic triterpenoids in leaves of Ilex aquifolium L. AB - Ilex leaves can utilize sucrose and mevalonate for the synthesis of triterpene esters. Mevalonate is also used for the synthesis of free triterpenoid alcohols, but sucrose is not. The selectivity of precursor utilization indicates separate sites for triterpenol and triterpenol-ester synthesis. The sites of synthesis are not found at the main locations of accumulation of triterpenols (the epicuticular wax) or triterpene esters (the cytoplasmatic lipid globules). Transport from the site of synthesis to the lipid globules, and especially towards the epicuticular wax, is slow. PMID- 24241312 TI - The correlation between crassulacean acid metabolism and water uptake in Senecio medley-woodii. AB - The combination of a chamber for CO2 gas exchange with a potometric measuring arrangement allowed concomitant investigations into CO2 gas exchange, transpiration and water uptake by the roots of whole plants of Senecio medley woodii, a species which exhibits Crassulacean acid metabolism. The water-uptake rate showed the same daily pattern as malate concentration and osmotic potential. The accumulation of organic acids resulting from nocturnal CO2 fixation enhanced the water-uptake rate from dusk to dawn. During the day the water-uptake rates decreased with decreasing organic-acid concentration. With gradually increasing water stress, CO2 dark fixation of S. medley-woodii was increased as long as water could be taken up by the roots. It was also shown that a reestablished water supply after drought caused a similar increase which in both cases ameliorated the water uptake in order to conserve a positive water balance for as long as possible. This water-uptake pattern shows that Crassulacean acid metabolism is not only a water-saving adaptation but also enhances water uptake and is directly correlated with the amelioration of the plant water status. PMID- 24241313 TI - Waxmonoester fermentation in Euglena gracilis T. Factors favouring the synthesis of odd-numbered fatty acids and alcohols. AB - Waxmonoester fermentation at the expense of endogenous paramylon was followed in the dark in autotrophically grown Euglena gracilis. With reduced oxygen tension and decreasing O2-consumption rates the proportion of odd-numbered fatty acids and alcohols increased up to a molar ratio of nearly 1:1 under strictly anaerobic conditions. Labelled (14)CO2, succinate and propionate were incorporated into odd numbered fatty acids and alcohols 11 to 33 times faster than in even-numbered chains. The electron-flow inhibitor rotenone diminished waxester formation in total, but especially CO2 fixation and the synthesis of odd-numbered chains, without impeding anaerobic carbohydrate breakdown. These findings are indicative for propionyl-CoA as an intermediate in the synthesis of odd-numbered chains. Its probable synthesis in the methylmalonyl-CoA pathway is discussed with regard to energetics. PMID- 24241314 TI - Fatty-acid synthesis in plastids from maturing safflower and linseed cotyledons. AB - Plastids isolated from maturing, nongreen safflower (Carthamus tinctorius L.) cotyledons yielded unesterified fatty acids as the predominant product of fatty acid synthesis from [1-(14)C]acetate. Exogenous reduced pyridine nucleotides were not required for this synthesis, but [1-(14)C]acetate incorporation was absolutely dependent on addition of ATP. Linseed (Linum usitatissimum L.) cotyledons are green during development and plastids isolated from them resembled leaf chloroplasts with developed grana. In contrast to the safflower plastids, those from linseed were able to carry out fatty-acid synthesis at low irradiances without the addition of either pyridine nucleotides or ATP. Intact linseed cotyledons were capable of net photosynthesis at rates up to 95 MUmol.mg(-1) chlorophyll.h(-1). However, the low-light environment inside the linseed capsule (approx. 15% of external) means that photosynthesis will not contribute appreciably to the carbon economy of the developing seed and its main role may be to supply cofactors for fatty-acid synthesis. PMID- 24241315 TI - Effects of temperature at constant air dew point on leaf carboxylation efficiency and CO2 compensation point of different leaf types. AB - The effect of temperature on photosynthesis at constant water-vapor pressure in the air was investigated using two sclerophyll species, Arbutus unedo and Quercus suber, and one mesophytic species, Spinacia oleracea. Photosynthesis and transpiration were measured over a range of temperatures, 20-39 degrees C. The external concentration of CO2 was varied from 340 MUbar to near CO2 compensation. The initial slope (carboxylation efficiency, CE) of the photosynthetic response to intercellular CO2 concentration, the CO2 compensation point (Gamma), and the extrapolated rate of CO2 released into CO2-free air (R i) were calculated. At an external CO2 concentration of 320-340 MUbar CO2, photosynthesis decreased with temperature in all species. The effect of temperature on Gamma was similar in all species. While CE in S. oleracea changed little with temperature, CE decreased by 50% in Q. suber as temperature increased from 25 to 34 degrees C. Arbutus unedo also exhibited a decrease in CE at higher temperatures but not as marked as Q. suber. The absolut value of R i increased with temperature in S. oleracea, while changing little or decreasing in the sclerophylls. Variations in Gamma and R i of the sclerophyll species are not consistent with greater increase of respiration with temperature in the light in these species compared with S. oleracea. PMID- 24241316 TI - Regulation of synthesis of nitrite reductase in pea leaves: in-vivo and in-vitro studies. AB - Crude protein extracts from leaves of pea (Pisum sativum L.) labeled with an L (14)C-amino-acid mixture or [(35)S]methionine, were treated with antibodies prepared against nitrite reductase (NiR; EC 1.6.6.4). When the immunoprecipitates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) a polypeptide with the same mobility as that of the native NiR was detected. By using darkened or illuminated leaves in the absence or presence of nitrate, it has been confirmed that nitrate is required in the in-vivo synthesis of NiR and that this synthesis is stimulated by light. Cell-free translation with a wheat-germ extract primed with polysomes from illuminated leaves treated with nitrate yielded polypeptides of a wide range of molecular weights (Mrs). Two polypeptides were immunoprecipitated from the translational products by anti-NiR serum. The mobility of one of them on SDS-PAGE corresponded to that of NiR while the other had a slightly higher Mr. It is concluded that NiR is synthesized as a heavy-molecular-weight precursor. Nitrate appears to regulate NiR synthesis by triggering transcription whereas the light may control the level of transcription or translation. PMID- 24241317 TI - Use of a pH-response curve for growth to predict apparent wall pH in elongating segments of maize coleoptiles and sunflower hypocotyls. AB - To determine the relationship between apparent pH of the wall solution and shoot segment elongation, curves for the initial growth rates as a function of pH of the external solution were determined for maize (Zea mays L.) coleoptiles and sunflower (Helianthus annuus L.) hypocotyls and used to predict apparent wall pH in segments responding to indole-3-acetic acid (IAA) and fusicoccin (FC). When a solution having a pH predicted for walls of coleoptile segments responding to IAA was applied to the segments in the presence of IAA, this pH was not maintained. However, when the same was done for coleoptile segments responding to FC, the predicted pH was maintained in the external solution. Sunflower hypocotyl tissue did not maintain the external pH at the predicted value in the presence of either IAA or FC. The results indicate that wall loosening in coleoptiles caused by IAA may not be solely controlled by pH in the wall, yet growth (wall loosening) caused by FC apparently is directly related to wall pH. In sunflower the growth response to neither IAA nor FC appears to be directly correlated with wall pH. PMID- 24241318 TI - A light-enhanced metabolism of sulfite in cells of Cucumis sativus L. cotyledons. AB - The effects of light and several photosynthetic inhibitors on the rate of sulfite metabolism in cells obtained from Cucumis sativus L. cotyledons was studied. The cells were treated with 200 MUM Na2SO3 and the disappearance of sulfite was monitored using either dithiobisnitrobenzoic acid or fuchsin. The rate of sulfite disappearance in light was double the dark rate. Disalicylidene propanediamine at 1 mM increased this light-enhanced metabolism approx. 50%; neither 1 MUM 3,4 dichlorophenyl-N,N-dimethylurea nor 0.1 mM cyanazine, which completely inhibited CO2-dependent oxygen evolution, affected the rate of sulfite metabolism. Addition of 200 MUM Na2SO3 to the cells partially inhibited (14)CO2 fixation. The rate of sulfite consumption by the cells did not affect this inhibition. We conclude that light-dependent sulfite metabolism is cucumber cells may utilize reduced ferredoxin generated as a result of photosynthetic electron transport. An injurious interaction between CO2 fixation and sulfite appears to occur independently of the sulfite-metabolism process. PMID- 24241319 TI - Purification and characterization of thylakoid-bound Mn-superoxide dismutase in spinach chloroplasts. AB - Thylakoid-bound superoxide dismutase (SOD; EC 1.15.1.1) was solubilized by Triton X-100 from spinach and purified to a homogeneous state. The molecular weight of thylakoid-bound SOD was 52000; the enzyme was composed of two equal subunits. Its activity was not sensitive to cyanide and hydrogen peroxide, and the isolated SOD contained Mn, but neither Fe nor Cu. Thus, the thylakoid-bound SOD is a Mn containing enzyme. The subunit molecular weight of thylakoid Mn-SOD is the highest among Mn-SODs isolated so far, a fact which might reflect its binding to the membranes. PMID- 24241320 TI - Heat modification of ribulose-1,5-bisphosphate carboxylase/oxygenase by temperature pretreatment of wheat (Triticum aestivum L.) seedlings. AB - The effect of low-, ambient- and high-temperature pretreatments (48 h at 4 degrees C, 20 degrees C or 36 degrees C) of wheat seedlings (spring wheat Triticum aestivum L., cv. Kolibri) on the solubility properties of ribulose-1,5 bisphosphate carboxylase/oxygenase (RuBPCase; EC 4.1.1.39) was studied. The extractable protein moiety of heat-pretreated plants exhibited increased solubility in dilute buffer (50 mM k-phosphate, pH 6.8), compared with protein extracted from 4 degrees C- or 20 degrees C-plants. The salting-out characteristics for ammonium-sulfate precipitation confirmed this finding since a delayed precipitation of extractable protein from 36 degrees C-plants was observed. Using polyacrylamide gel electrophoresis, the in-vivo temperature induced differences in protein solubility could be traced back to a change in the solubility of RuBPCase. The RuBPCase was purified from wheat seedlings, and the purified enzyme also exhibited differential solubility. In order to evaluate this further, purified RuBPCase was subjected to probing for conformational properties. A decrease of fluorescence of the RuBPCase 1-anilino-8-naphtalene sulfonate complex revealed that the RuBPCase from 36 degrees C-plants had a more hydrophilic protein surface. Titration of the sulfhydryl groups of native RuBP Case with 5,5'-dithiobis (2-nitrobenzoic acid) pointed to a reduced accessibility of the R-SH groups in the case of the 36 degrees C-type of RuBPCase. The large subunit of RuBPCase from 4 degrees C/20 degrees C-plants tended to give rise to an artificial lower-molecular-weight polypeptide which could not be found in crude or purified RuBPCase from heat-pretreated wheat seedlings. PMID- 24241321 TI - Composition of the cell walls of Nicotiana alata Link et Otto pollen tubes. AB - Cell walls isolated from pollen of Nicotiana alata germinated in vitro contain glucose and arabinose as the predominant monosaccharides. Methylation analysis and cytochemical studies are consistent with the major polysaccharides being a (1 >3)-beta-D-glucan (callose) and an arabinan together with small amounts of cellulose. The cell walls contain 2.8% uronic acids. Alcian blue stains the pollen-tube walls intensely at the tip, indicating that acidic polysaccharides are concentrated in the tip. Synthetic aniline-blue fluorochrome is specific primarily for (1->3)-beta-D-glucans and stains the pollen-tube walls, except at the tip. Protein (1.5%), containing hydroxyproline (2.4%), is present in the cell wall. PMID- 24241322 TI - Chloroplast movement in Mougeotia induced by blue light pulses. AB - The profile-to-face chloroplast movement in the green alga Mougeotia has been induced by strong blue and near-ultraviolet light pulses (6 J m(-2)). Simultaneously, strong red or far-red light (10 W m(-2)) was applied perpendicularly to the inducing beam. The response was measured photometrically. Against the far-red background the reciprocity law was found to hold for pulse durations varying two orders of magnitude. The action spectrum exhibited a maximum near 450 nm and a distinct increase in near-ultraviolet. The time-course and the spectral dependence of pulse responses of chloroplasts in Mougeotia were similar to those recorded for other plants which are sensitive only to blue. This points to an alternative sensor system active in the short-wavelength region in addition to the phytochrome system. PMID- 24241323 TI - Amino-acid-transport mutant of Nicotiana tabacum L. AB - The uptake rates of 16 amino acids were measured in leaf discs from Nicotiana tabacum L., cv. Xanthi (wild type) and from two valine-resistant mutants, Val(r) 1 and Val(r)-2. For all amino acids tested the uptake rates in Val(r)-1 were similar to those in the wild type. The Val(r)-2 mutant showed a reduced uptake of neutral and acidic amino acids, but uptake of the basic amino acids was only slightly lower than in the wild type. It is argued that two systems for amino acid transport are present: one for neutral and acidic amino acids and the other for basic amino acids. PMID- 24241325 TI - Laparoscopic repair of post-abdominoperineal resection hernia: biological mesh and augmentation technique. AB - Perineal hernias are infrequent complications following abdominoperineal surgeries. These hernias require surgical repair when they become symptomatic by several conventional or reconstructive techniques. The benefits of a full laparoscopic approach and/or the combined approach of a perineal repair of the pelvic floor associated to the laparoscopic placement of a traditional synthetic mesh have been previously demonstrated. In this article, we present the case of a perineal incisional hernia, post-abdominoperineal resection of the rectum after radio chemotherapy, in the neoadjuvant treatment of a rectal adenocarcinoma tumor. An alternative approach, not previously described for the surgical repair of this type of hernia, is presented to assess the feasibility of the suturing repair, and efficacy of a biological acellular porcine collagen implant Permacol((r)). A full laparoscopic suturing for the closure of the perineal defect associated to biological mesh reinforcement was successfully undertaken, with good short-term outcomes. PMID- 24241326 TI - An estimation of inguinal hernia epidemiology adjusted for population age structure in Tanzania. AB - PURPOSE: Surgical conditions represent a significant source of global disease burden. Little is known about the epidemiology of inguinal hernia in resource poor settings. We present a method to estimate inguinal hernia disease burden in Tanzania. METHODS: Using data from the United States National Health and Nutrition Examination Survey (NHANES) prospective cohort study and Tanzanian demographic figures, we calculated inguinal hernia incidence and prevalence in Tanzanian adults under three surgical rate scenarios. Gender-specific incidence figures from NHANES data were adjusted according to Tanzanian population age structure. Hernia duration was adjusted for Tanzanian life expectancy within each age group. RESULTS: The prevalence of inguinal hernia in Tanzanian adults is 5.36% while an estimated 12.09% of men had hernias. Today, 683,904 adults suffer from symptomatic inguinal hernia in Tanzania. The annual incidence of symptomatic hernias in Tanzanian adults is 163 per 100,000 population. At Tanzania's current hernia repair rate, a backlog of 995,874 hernias in need of repair will develop over 10 years. 4.4 million disability-adjusted life-years would be averted with repair of prevalent symptomatic hernias in Tanzania. CONCLUSIONS: Our data indicate the extent of inguinal hernia disease burden in Tanzania. By adjusting our figures for the age structure of Tanzania, we have demonstrated that while the incidence of symptomatic cases may be lower than previously thought, prevalence of inguinal hernia in Tanzania remains high. This approach provides an update to our previously described methodology for calculation of inguinal hernia epidemiology in resource-poor settings that may be used in multiple country contexts. PMID- 24241327 TI - An estimate of hernia prevalence in Sierra Leone from a nationwide community survey. AB - PURPOSE: A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration, strangulation, or giant scrotal hernias. However, no representative population-based data are available to quantify the prevalence of hernias. We present data on groin masses in Sierra Leone to estimate prevalence, barriers to care, and associated disability. METHODS: A cluster randomized, cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination. Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care. RESULTS: Information was obtained from 3,645 respondents in 1,843 households, of which 1,669 (46%) were male and included in the study. In total, 117 males or 7.01% (95% CI 5.64-8.38) reported a soft or reducible swelling likely representing a hernia with four men having two masses. Of the 93.2% who indicated the need for health care, only 22.2% underwent a procedure, citing limited funds (59.0%) as the major barrier to care. On disability assessment, 20.2% were not able to work secondary to the groin swelling. CONCLUSIONS: The results indicate groin masses represent a major burden for the male population in Sierra Leone. Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity. PMID- 24241328 TI - Reply to: invited comment "Chronic pain and quality of life after transinguinal preperitoneal (TIPP) inguinal hernia repair: a few tips on TIPP". D.C. Chen and P. Amid. DOI 10.1007/s10029-013-1138-z. PMID- 24241329 TI - Genetic diversity of Pleurotus pulmonarius revealed by RAPD, ISSR, and SRAP fingerprinting. AB - Pleurotus pulmonarius is one of the most widely cultivated and popular edible fungi in the genus Pleurotus. Three molecular markers were used to analyze the genetic diversity of 15 Chinese P. pulmonarius cultivars. In total, 21 random amplified polymorphic DNA (RAPD), 20 inter-simple sequence repeat (ISSR), and 20 sequence-related amplified polymorphism (SRAP) primers or primer pairs were selected for generating data based on their clear banding profiles produced. With the use of these RAPD, ISSR, and SRAP primers or primer pairs, a total of 361 RAPD, 283 ISSR, and 131 SRAP fragments were detected, of which 287 (79.5 %) RAPD, 211 (74.6 %) ISSR, and 98 (74.8 %) SRAP fragments were polymorphic. Unweighted Pair-Group Method with Arithmetic Mean (UPGMA) trees of these three methods were structured similarly, grouping the 15 tested strains into four clades. Subsequently, visual DNA fingerprinting and cluster analysis were performed to evaluate the resolving power of the combined RAPD, ISSR, and SRAP markers in the differentiation among these strains. The results of this study demonstrated that each method above could efficiently differentiate P. pulmonarius cultivars and could thus be considered an efficient tool for surveying genetic diversity of P. pulmonarius. PMID- 24241330 TI - Sequencing, characterization, and gene expression analysis of the histidine decarboxylase gene cluster of Morganella morganii. AB - The histidine decarboxylase gene cluster of Morganella morganii DSM30146(T) was sequenced, and four open reading frames, named hdcT1, hdc, hdcT2, and hisRS were identified. Two putative histidine/histamine antiporters (hdcT1 and hdcT2) were located upstream and downstream the hdc gene, codifying a pyridoxal-P dependent histidine decarboxylase, and followed by hisRS gene encoding a histidyl-tRNA synthetase. This organization was comparable with the gene cluster of other known Gram negative bacteria, particularly with that of Klebsiella oxytoca. Recombinant Escherichia coli strains harboring plasmids carrying the M. morganii hdc gene were shown to overproduce histidine decarboxylase, after IPTG induction at 37 degrees C for 4 h. Quantitative RT-PCR experiments revealed the hdc and hisRS genes were highly induced under acidic and histidine-rich conditions. This work represents the first description and identification of the hdc-related genes in M. morganii. Results support the hypothesis that the histidine decarboxylation reaction in this prolific histamine producing species may play a role in acid survival. The knowledge of the role and the regulation of genes involved in histidine decarboxylation should improve the design of rational strategies to avoid toxic histamine production in foods. PMID- 24241332 TI - A scanning electron microscope study of interactions between micro-organisms andGaeumannomyces graminis (Syn.Ophiobolus graminis) on wheat roots. AB - Roots of wheat grown in unsterilized sand inoculated withGaeumannomyces graminis (Sacc.) von Arx and Olivier were examined by scanning electron microscopy. Healthy roots had a mucilaginous covering and were sparsely colonized by bacteria, but asG. graminis colonized the roots the mucilage disappeared and the numbers of bacteria on the surface increased. Lysis of the hyphae occurred, apparently caused by bacteria that colonized the hyphae. Inoculation of wheat in axenic culture with a strain ofPseudomonas fluorescens that was antagonistic toG. graminis in agar gave some protection against the pathogen; lysis of hyphae was observed where protection occurred. PMID- 24241331 TI - Functional conservation of RNase III-like enzymes: studies on a Vibrio vulnificus ortholog of Escherichia coli RNase III. AB - Bacterial ribonuclease III (RNase III) belongs to the RNase III enzyme family, which plays a pivotal role in controlling mRNA stability and RNA processing in both prokaryotes and eukaryotes. In the Vibrio vulnificus genome, one open reading frame encodes a protein homologous to E. coli RNase III, designated Vv RNase III, which has 77.9 % amino acid identity to E. coli RNase III. Here, we report that Vv-RNase III has the same cleavage specificity as E. coli RNase III in vivo and in vitro. Expressing Vv-RNase III in E. coli cells deleted for the RNase III gene (rnc) restored normal rRNA processing and, consequently, growth rates of these cells comparable to wild-type cells. In vitro cleavage assays further showed that Vv-RNase III has the same cleavage activity and specificity as E. coli RNase III on RNase III-targeted sequences of corA and mltD mRNA. Our findings suggest that RNase III-like proteins have conserved cleavage specificity across bacterial species. PMID- 24241333 TI - Effects ofFlavobacterium lutescens growth on populations ofEscherichia coli andStreptococcus faecalis in water following thermal loading. AB - Flavobacterium lutescens has been observed to constitute a major segment of the aerobic, heterotrophic bacterial populations in nonpolluted aquatic systems. It is present in lesser numbers in the presence of municipal sewage and higher concentrations of organic wastes. In laboratory tests, in water from nonpolluted systems, this species became the predominant bacterial type following thermal addition. When temperature was increased in water from polluted sources,F. lutescens became a major component of the bacterial populations. In the laboratory, the numbers ofEscherichia coli andStreptococcus faecalis were observed to decrease in proportion to the increase inF. lutescens after thermal addition. Similar results were observed when water from three aquatic systems of differing nutrient content was tested. A greater amount of organic material present in the water reduced the predominance ofF. lutescens. These results indicate that, without use of chemical additives, this method may be useful for restoration of natural aquatic bacterial populations and reduction of undesirable microbial populations in water supplies. PMID- 24241334 TI - Ultrastructural basis of sclerotial survival in soil. AB - The ultrastructure of developing and mature sclerotia ofSclerotium rolfsii was studied with a scanning electron microscope. The mature sclerotium is disconnected from the mycelium and well differentiated. The rind is composed of rather thick-walled empty cells. The cortex cells are large and almost completely filled with vesicles, whereas the medullar cells are smaller and some of them are very thickwalled. PMID- 24241335 TI - Circadian chronotypic death in heat-synchronized infradian mode cultures ofTetrahymena pyriformis W. AB - Continuous cultures ofTetrahymena pyriformis in the infradian ("slow exponential") growth mode can be entrained to give circadian rhythms of cell division by the application of thermal cycles with periods of 24 hr. The degree of synchronization (phasing index) is dependent on the cycling of other environmental agents, particularly food in the form of the defined medium used. The phase angles of these multiple zeitgebers to one another and to the circadian cell cycle markedly influence the quality of synchronization achieved. In wellsynchronized oxygen-limited cultures, a circadian cytotoxia (circadian chronotypic death) is observed when the culture's oxygen requirements periodically exceed the oxygen support limit of the environment. PMID- 24241336 TI - Microbial film development in a trickling filter. AB - The transmission and scanning electron microscopes were employed to visualize the sequence of the biofilm development in the trickling wastewater filter. After the deposit of a small amount of debris upon a hard surface, the bacterial cells attach and develop the matrix on which the biofilm is formed. Protozoa invade the basic layer where they feed on the bacteria. The algae are seeded upon the bacterial matrix and grow so profusely that the bacteria must develop aerial colonies in the competition for food and oxygen. Destruction of the bacteria in the matrix and the weight and hydraulic pressure cause detachment of the biofilm and a new matrix must be developed. PMID- 24241337 TI - Bacterial attack of corals in polluted seawater. AB - Coral heads of the genusPlatigyra exposed to low concentrations of crude oil, copper sulfate, potassium phosphate, or dextrose were killed in periods of 5 to 10 days in aquarium studies. The chemicals stimulated the production of large quantities of mucus by the corals. In aquaria treated with antibiotics to prevent microbial growth,Platigyra survived the presence of these chemicals in the water, indicating a role of the microflora in the death of the corals. Evidence was obtained implicating predatory bacteria,Desulfovibrio andBeggiatoa, in the destruction of the stressed coral colonies. PMID- 24241338 TI - Observations on estuarine microfouling using the scanning electron microscope. AB - Scanning electron microscopy was used to observe microbiological primary fouling of glass surfaces exposed in estuarine waters. Observations on clean glass, and glass treated with water-repellent coatings, showed that bacterial slimes adhered less strongly to the waterrepellent glass. An experiment using pure cultures of bacteria and latex particles showed that attached bacteria promoted the settlement of latex particles on the glass. PMID- 24241339 TI - Diagnosis of type 1 diabetes within the first five years of life influences quality of life and risk of severe hypoglycemia in adulthood. AB - Progressive adaptation to disease is paramount to improve quality of life (QoL) and other psychological dimensions in type 1 diabetes (T1DM). This study aimed at identifying possible correlations between QoL, locus of control (LoC) and clinical variables in patients with T1DM followed up for 16 years. Fifty-nine patients (27 women) with T1DM, part of a cohort of 112 followed since 1996, accepted to participate. Patients were divided into those in whom onset of T1DM had been during the first 5 years of life (n = 16) or later. They were also stratified into worsened, stable and improved, based on whether their HbA1c had increased/decreased by 1 percentage point between baseline and last follow-up visit. QoL was measured by the Diabetes Quality of Life questionnaire (DQOL), translated into Italian and re-validated. The LoC was measured by the Peyrot- and Rubin-specific questionnaire. Patients who developed T1DM before age 5 had a better total DQOL score than those who developed it later in life, mainly due to the satisfaction dimension and a tendency to decreased fatalism in adult age. All subjects whose HbA1c had worsened from baseline had had their diagnosis after age 5 and reported more frequent episodes of hypoglycemia. Onset of diabetes after age 5 and more frequent hypoglycemia was more likely in subjects with worsened HbA1c (ORs 7.6, p < 0.10 and 20.3, p < 0.01, respectively, from a multivariate logistic model with HbA1c, dichotomized in 'worsened' vs all others, as dependent variable). Onset of T1DM during the first 5 years of life may result in better QoL and less fatalism in the long term. Presumably, these patients have no memory of disease onset, which may reduce trauma and facilitate adaptation to managing life with diabetes. PMID- 24241340 TI - A multi-wave study of organizational justice at work and long-term sickness absence among employees with depressive symptoms. AB - OBJECTIVES: Mental health problems are strong predictors of long-term sickness absence (LTSA). In this study, we investigated whether organizational justice at work - fairness in resolving conflicts and distributing work - prevents risk of LTSA among employees with depressive symptoms. METHODS: In a longitudinal study with five waves of data collection, we examined a cohort of 1034 employees with depressive symptoms. Depressive symptoms and organizational justice were assessed by self-administered questionnaires and information on LTSA was derived from a national register. Using Poisson regression analyses, we calculated rate ratios (RR) for the prospective association of organizational justice and change in organizational justice with time to onset of LTSA. All analyses were sex stratified. RESULTS: Among men, intermediate levels of organizational justice were statistically significantly associated with a decreased risk of subsequent LTSA after adjustment for covariates [RR 0.49, 95% confidence interval (95% CI) 0.26-0.91]. There was also a decreased risk for men with high levels of organizational justice although these estimates did not reach statistical significance after adjustment (RR 0.47, 95% CI 0.20-1.10). We found no such results for women. In both sexes, neither favorable nor adverse changes in organizational justice were statistically significantly associated with the risk of LTSA. CONCLUSIONS: This study shows that organizational justice may have a protective effect on the risk of LTSA among men with depressive symptoms. A protective effect of favorable changes in organizational justice was not found. PMID- 24241342 TI - The potential of neutrophil elastase inhibitors as anti-inflammatory therapies. AB - PURPOSE OF REVIEW: Therapeutic inhibition of neutrophil-derived elastases holds promise with powerful treatment effects observed in various preclinical models of lung, bowel and skin inflammation and ischaemia-reperfusion injury relevant to myocardial infarction, stroke and transplant medicine. RECENT FINDINGS: This brief review considers recent studies eliciting the complex interaction between neutrophil-derived elastases and endogenous inhibitors that determines elastase mediated inflammation in humans. Translating results of preclinical studies with neutrophil elastase inhibitors remains challenging. Future clinical studies will harness developments in drug delivery and utilize more specific markers of neutrophil elastase activity to inform on the efficacy of inhibition. A summary of recently published and ongoing clinical trials with synthetic inhibitors sivelestat and AZD9668 and recombinant elafin is provided. SUMMARY: Clinical trials with neutrophil elastase inhibitors in lung and cardiovascular disease are ongoing, and future studies will incorporate novel delivery approaches and be directed by specific markers of neutrophil-derived elastase activity to target inhibition to the sites of inflammatory tissue injury. PMID- 24241341 TI - From boron cluster to two-dimensional boron sheet on Cu(111) surface: growth mechanism and hole formation. AB - As attractive analogue of graphene, boron monolayers have been theoretically predicted. However, due to electron deficiency of boron atom, synthesizing boron monolayer is very challenging in experiments. Using first-principles calculations, we explore stability and growth mechanism of various boron sheets on Cu(111) substrate. The monotonic decrease of formation energy of boron cluster B(N) with increasing cluster size and low diffusion barrier for a single B atom on Cu(111) surface ensure continuous growth of two-dimensional (2D) boron cluster. During growth process, hexagonal holes can easily arise at the edge of a 2D triangular boron cluster and then diffuse entad. Hence, large-scale boron monolayer with mixed hexagonal-triangular geometry can be obtained via either depositing boron atoms directly on Cu(111) surface or soft landing of small planar BN clusters. Our theoretical predictions would stimulate further experiments of synthesizing boron sheets on metal substrates and thus enrich the variety of 2D monolayer materials. PMID- 24241343 TI - Stereoselective binding of doxazosin enantiomers to plasma proteins from rats, dogs and humans in vitro. AB - AIM: (+/-)Doxazosin is a long-lasting inhibitor of alpha1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. METHODS: Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. RESULTS: Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [(-)doxazosin: 89.4%-94.3%; (+)doxazosin: 90.9%-95.4%]. (+)Doxazosin exhibited significantly higher protein binding capacities than (-)doxazosin in all the three species, and the difference in the bound concentration (Cb) between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog>human>rat. CONCLUSION: (-)Doxazosin and (+)doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans. PMID- 24241344 TI - Synthesis and bioassay of beta-(1,4)-D-mannans as potential agents against Alzheimer's disease. AB - AIM: Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Abeta peptide toxicity in vitro. METHODS: The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Abeta1-40 (2 MUmol/L), and the cell viability was detected using a CCK8 assay. RESULTS: A series of beta-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 MUmol/L beta (1,4)-D-mannobiose 6, beta-(1,4)-D-mannotriose 9 or beta-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Abeta1-40-induced toxicity. The efficacies were similar to those caused by 10 MUmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. CONCLUSION: Synthetic homogeneous short chain beta-(1,4)-D-mannans shows neuroprotective effect against Abeta peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed. PMID- 24241345 TI - The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects. AB - Traumatic brain injury is the leading cause of morbidity and mortality in young adults. The secondary injury in traumatic brain injury consists of a complex cascade of processes that simultaneously react to the primary injury to the brain. This cascade has been the target of numerous therapeutic agents investigated over the last 30 years, but no neuroprotective treatment option is currently available that improve neurological outcome after traumatic brain injury. Progesterone has long been considered merely a female reproductive hormone. Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans. Here, we review the increasing evidence that progesterone can act as a neuroprotective agent to treat traumatic brain injury and the mechanisms underlying these effects. Additionally, we discuss the current progress of clinical studies on the application of progesterone in the treatment of traumatic brain injuries. PMID- 24241346 TI - PIK3CA hypomethylation plays a key role in activation of the PI3K/AKT pathway in esophageal cancer in Chinese patients. AB - AIM: To investigate the role of PIK3CA oncogene in tumorigenesis and development of esophageal cancer in Chinese patients at the levels of genetic mutation and epigenetics. METHODS: Seventy six esophageal tumor samples and corresponding adjacent normal tissues were collected, and the genomic DNA was extracted. Mutations in the 9th and 20th exons of PIK3CA gene were detected using conventional sequencing. PIK3CA methylation rates in two selected CpG islands (CpG island 1 and 2) were detected using sub-bisulfate modified sequencing. P110alpha and pAKT expression levels were detected with Western blotting. RESULTS: In PIK3CA gene of the tumor tissues, G1633C (E545Q) mutation was detected in the 9th exon with a rate of 3.95% (3/76), whereas mutation was not found in the 20th exon. Nor mutation did occur in PIK3CA gene of the adjacent normal tissues. The methylation rate of the CpG island 1 had no significant difference between the tumor and adjacent tissues (0.77%+/-0.009% vs 0.89%+/ 0.008%), but the methylation rate of the CpG island 2 in the esophageal tumors was significantly lower than that in the adjacent tissues (6.00%+/-2.80% vs 10.45%+/-5.51%). Furthermore, the rate of methylation of the CpG island 2 in TNM stage III and IV esophageal cancer (3.84%+/-2.08%) was significantly lower than in stage I (8.52%+/-2.55%) and stage II (6.42%+/-2.36%). PIK3CA gene hypomethylation in esophageal cancer was significantly correlated with high expression of p110alpha. CONCLUSION: PIK3CA gene hypomethylation plays a key role in the tumorigenesis and development of esophageal cancer in Chinese patients, while the mutations of PIK3CA gene have little effect on the development of esophageal cancer. PMID- 24241347 TI - Ketanserin improves cardiac performance after myocardial infarction in spontaneously hypertensive rats partially through restoration of baroreflex function. AB - AIM: Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction (MI). Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved. METHODS: Spontaneously hypertensive rats (SHR) were treated with ketanserin (0.3 mg.kg( 1).d(-1)). Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) in ischemic myocardium, angiogenesis, cardiac function, and left ventricular (LV) remodeling were evaluated subsequently. RESULTS: Ketanserin significantly improved baroreflex sensitivity (0.62+/-0.21 vs 0.34+/-0.12 ms/mmHg, P<0.01) and vagal tonic activity (heart rate changes in response to atropine, 54.8+/-16.2 vs 37.6+/-13.4 bpm, P<0.01) without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin prominently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and alpha7-nAChR in ischemic myocardium. CONCLUSION: Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI. PMID- 24241348 TI - Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins. AB - The sequencing of the human genome has fueled the last decade of work to functionally characterize genome content. An important subset of genes encodes membrane proteins, which are the targets of many drugs. They reside in lipid bilayers, restricting their endogenous activity to a relatively specialized biochemical environment. Without a reference phenotype, the application of systematic screens to profile candidate membrane proteins is not immediately possible. Bioinformatics has begun to show its effectiveness in focusing the functional characterization of orphan proteins of a particular functional class, such as channels or receptors. Here we discuss integration of experimental and bioinformatics approaches for characterizing the orphan membrane proteome. By analyzing the human genome, a landscape reference for the human transmembrane genome is provided. PMID- 24241349 TI - Hsp90 inhibitor BIIB021 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53-MDM2 balance. AB - AIM: To investigate the effects of BIIB021, an inhibitor of heat shock protein 90 (Hsp90) alone or in combination with triptolide (TPL) on T-cell acute lymphoblastic leukemia (T-ALL) and the mechanisms of action. METHODS: Human T-ALL cells line Molt-4 was examined. The cell viability was measured using MTT assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. RESULTS: Treatment of Molt-4 cells with BIIB021 (50-800 nmol/L) inhibited the cell growth in a dose dependent manner (the IC50 value was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h). BIIB021 dose-dependently induced G0/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BIIB021 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BIIB021 (50-400 nmol/L) dose-dependently decreased the phospho MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL (5-40 nmol/L) dose-dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BIIB021 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53 MDM2 balance, thus markedly enhanced p53 activation. In addition, the co treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. CONCLUSION: The combination of BIIB021 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance. PMID- 24241350 TI - Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease. AB - AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg.kg(-1).d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-kappaB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-kappaB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF kappaB, cyclin D1, and PCNA expression. PMID- 24241351 TI - A new bisphosphonate derivative, CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway. AB - AIM: To investigate the effects of a new derivative of bisphosphonates, [2-(6 aminopurine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP), on human gastric cancer. METHODS: Human gastric cancer cell lines (SGC-7901, BGC-823, MKN 45, and MKN-28) and human colon carcinoma cell lines (LoVo and HT-29) were tested. Cell growth was determined using the MTT assay. Flow cytometry, Western blot, caspase activity assay and siRNA transfection were used to examine the mechanisms of anticancer action. Female BALB/c nude mice were implanted with SGC 7901 cells. From d6 after inoculation, the animals were injected with CP (200 MUg/kg, ip) or vehicle daily for 24 d. RESULTS: CP suppressed the growth of the 6 human cancer cell lines with similar IC50 values (3239 MUmol/L). In SGC-7901 cells, CP arrested cell cycle progression at the G2/M phase. The compound activated caspase-9, increased the expression of pro-apoptotic proteins Bax and Bad, decreased the expression of anti-apoptotic protein Bcl-2. Furthermore, the compound selectively activated ERK1/2 without affecting JNK and p38 in SGC-7901 cells. Treatment of SGC-7901 cells with the specific ERK1/2 inhibitor PD98059 or ERK1/2 siRNA hampered CP-mediated apoptosis. In the human gastric cancer xenograft nude mouse model, chronic administration of CP significantly retarded the tumor growth. CONCLUSION: CP is a broad-spectrum inhibitor of human carcinoma cells in vitro, and it also exerts significant inhibition on gastric cancer cell growth in vivo. CP induces human gastric cancer apoptosis via activation of the ERK1/2 signaling pathway. PMID- 24241352 TI - Yhhu3813 is a novel selective inhibitor of c-Met kinase that inhibits c-Met dependent neoplastic phenotypes of human cancer cells. AB - AIM: c-Met kinase deregulation is strongly associated with the formation, progression and dissemination of human cancers. In this study we identified Yhhu3813 as a small-molecule inhibitor of c-Met kinase and characterized its antitumor properties both in vitro and in vivo. METHODS: The activities of different kinases were measured using ELISA assays and signaling proteins in the cells were detected with Western blotting. Cell proliferation was assessed using SRB or MTT assay in twenty human cell lines and cell cycle distribution was determined with flow cytometry. Transwell-based assay was used to evaluate cell migration and invasion. Cell invasive growth was detected by a morphogenesis assay. c-Met overactivated human NSCLC cell line EBC-1 xenografts were used to evaluate the in vivo anti-tumor efficacy. RESULTS: Yhhu3813 potently inhibited c Met kinase activity in vitro with an IC50 value of 2.4+/-0.3 nmol/L, >400-fold higher than that for a panel of 15 different tyrosine kinases, suggesting a high selectivity of Yhhu3813. The compound (20, 100 and 500 nmol/L) dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and Erk signal cascades in multiple c-Met aberrant human cancer cell lines, regardless of the mechanistic complexity in c-Met activation across different cellular contexts. In 20 human cancer cell lines harboring different backgrounds of c-Met expression/activation, Yhhu3813 potently inhibited c-Met-driven cell proliferation via arresting cells at G1/S phase. Furthermore, Yhhu3813 substantially impaired c-Met-mediated cell migration, invasion, scattering, and invasive growth. Oral administration of EBC-1 xenograft mice with Yhhu3813 (50 or 100 mg.kg(-1).d(-1), qd, for 2 weeks) dose-dependently suppressed the tumor growth, which was correlated with a reduction in the intratumoral proliferation index and c-Met signaling. CONCLUSION: Yhhu3813 is a potent selective inhibitor of c-Met that inhibits c-Met-dependent neoplastic phenotypes of human cancer cells in vitro and in vivo. PMID- 24241353 TI - A systematic assessment of normalization approaches for the Infinium 450K methylation platform. AB - The Illumina Infinium HumanMethylation450 BeadChip has emerged as one of the most popular platforms for genome wide profiling of DNA methylation. While the technology is wide-spread, systematic technical biases are believed to be present in the data. For example, this array incorporates two different chemical assays, i.e., Type I and Type II probes, which exhibit different technical characteristics and potentially complicate the computational and statistical analysis. Several normalization methods have been introduced recently to adjust for possible biases. However, there is considerable debate within the field on which normalization procedure should be used and indeed whether normalization is even necessary. Yet despite the importance of the question, there has been little comprehensive comparison of normalization methods. We sought to systematically compare several popular normalization approaches using the Norwegian Mother and Child Cohort Study (MoBa) methylation data set and the technical replicates analyzed with it as a case study. We assessed both the reproducibility between technical replicates following normalization and the effect of normalization on association analysis. Results indicate that the raw data are already highly reproducible, some normalization approaches can slightly improve reproducibility, but other normalization approaches may introduce more variability into the data. Results also suggest that differences in association analysis after applying different normalizations are not large when the signal is strong, but when the signal is more modest, different normalizations can yield very different numbers of findings that meet a weaker statistical significance threshold. Overall, our work provides useful, objective assessment of the effectiveness of key normalization methods. PMID- 24241354 TI - Au@Cu2O core-shell nanoparticles as chemiresistors for gas sensor applications: effect of potential barrier modulation on the sensing performance. AB - Au@Cu2O core-shell nanoparticles (NPs) were synthesized by a solution method at room temperature and applied for gas sensor applications. Transmission electron microscopy (TEM) images showed the formation of Au@Cu2O core-shell NPs, where 12 15 nm Au NPs were covered with 60-30 nm Cu2O shell layers. The surface plasmon resonance (SPR) peak of Au NPs was red-shifted (520-598 nm) after Cu2O shell formation. The response of Au@Cu2O core-shell NPs was higher than that of bare Cu2O NPs to CO at different temperatures and concentrations. Similarly, the response of Au@Cu2O core-shell NPs was higher than that of bare Cu2O NPs for NO2 gas at low temperature. The improved performance of Au@Cu2O core-shell NPs was attributed to the pronounced electronic sensitization, high thermal stability and low screening effect of Au NPs. PMID- 24241355 TI - Antioxidative plant extracts for chemoprevention. PMID- 24241356 TI - Giant chylous cyst and ileal duplication in a young adult. AB - Alimentary tract duplications are rare congenital anomalies that usually present in childhood and occasionally in adults. They are most common in the ileum, but can occur anywhere along the alimentary tract from the mouth to the anus. We report a 24-year-old woman who presented with a giant chylous ileum cyst duplication. To our knowledge, there is only one other report of a patient with a giant chylous cyst in the literature. PMID- 24241357 TI - Morphological study of the attachment of sternocleidomastoid muscle. AB - INTRODUCTION: The sternocleidomastoid (SCM) muscle is a major muscle of the neck. Classically, this muscle is attached below the sternum and clavicle, although the mode of attachment might vary. As the SCM is related to numerous important neurovascular structures, its variable anatomy is clinically relevant, particularly for neck surgeries. A cadaveric study was performed to establish the variations present in the mode of attachment of the SCM muscle in an Indian population. METHODS: We studied the variations in the attachment of the SCM muscle during the dissection of 18 cadavers for undergraduate teaching in two medical colleges in West Bengal, India. RESULTS: Variations in the attachment of the SCM muscle were found in 5 (27.8%) specimens. Of these five specimens, three had unilateral variations and two had bilateral variations. In each specimen, the modes of presentation of the SCM and its fusion with the major bulk were also different. CONCLUSION: In this study, we found variations in the attachment of the SCM muscle in more than a quarter of the specimens dissected. Surgeons should bear in mind such variations when performing neck surgeries. PMID- 24241358 TI - Dural metastasis of nasopharyngeal carcinoma: rare, but worth considering. AB - Metastasis of nasopharyngeal carcinoma (NPC) to the dura, an extremely rare condition, can be symptomatically silent and mistaken for a benign entity radiographically. Missed diagnosis can lead to serious consequences or prove immediately fatal. We report a woman with dural metastasis of NPC that mimicked a meningioma on radiography. Craniectomy with tumour resection was performed due to rapid progression from the onset of symptoms to disability. The patient was still alive two years after surgery. This case emphasises the need to keep in mind the possibility of dural metastasis of NPC in patients with abnormal imaging features. This would not only avoid wrong and optimistic diagnosis, but also allow for appropriate treatment in a timely manner. To our knowledge, this is the first report of metastasis of NPC to the dura. We provide detailed information on the neoplastic lesion, which masqueraded as a benign entity and caused potentially fatal consequences. PMID- 24241359 TI - MiR-155 up-regulation by LMP1 DNA contributes to increased nasopharyngeal carcinoma cell proliferation and migration. AB - Regulation of oncogenic or tumor-suppressive microRNAs expression by Epstein-Barr virus (EBV) and the correlation of EBV with the nasopharyngeal carcinoma (NPC) have cast new light on the cause of NPC. The present study is to determine the association of miR-155 with EBV-positive NPC, and to evaluate the oncogenic role of miR-155 in cell proliferation, migration and invasion of NPC cells. The miR 155 expression was determined by real-time RT-qPCR; The oncogenic promotion of miR-155 was evaluated by by cell colony formation assay, proliferation assay, scratch assay and transwell migration assay. It showed that miR-155 expression was up-regulated in EBV-positive NPC tissue samples and was correlated with plasma LMP1 DNA copies. Expression of miR-155 was also up-regulated in NPC cell lines post-transfecting with LMP1-expressing plasmid. Up-regulated miR-155 stimulated the capability of NPC cell proliferation, colony formation, cell migration and invasion. Therefore, miR-155 is up-regulated in NPC tissues, with a correlation with plasma LMP1 DNA copies, and is significantly induced in NPC cells by LMP1 in vitro. The oncogenic miR-155 promotes NPC cell proliferation, migration and invasion significantly in vitro. PMID- 24241360 TI - Deep neck space abscesses of dental origin: the impact of Streptococcus group Milleri. AB - In recent years, there has been rising interest in Streptococcus group Milleri (SM) because high mortality rates have been related to it. In case of deep neck infections (DNI), whatever the origin, mortality rates as high as 26% were reported. But there are no data available for DNI with SM of purely dental origin. The aim of our article was to describe and analyse DNI of purely dental origin involving on one hand SM and on the other hand infections without presence of SM. We compared these two groups and statistically investigated if there were differences in clinical presentation (age, mouth opening, length of hospital stay, laboratory parameters) or clinical behaviour (re-operation, re hospitalisation, secondary osteomyelitis, stay at intensive care, length of antibiotic treatment, presence of resistances against antibiotics, incapacity to work). For this, we retrospectively searched medical records of our institution for all purulent DNI treated from 2004 till 2012. We found 81 patients meeting all inclusion criteria. Thirty-four patients had involvement of SM, 47 did not. The only statistically significant difference between the SM group and the non-SM group was the length of incapacity to work. All other parameters were non significant. Furthermore, there were no fatalities. In conclusion, the clinical importance of this article is that patients with deep neck abscesses of purely dental origin involving SM do not need more or different care when compared to all other DNI of dental origin. PMID- 24241361 TI - Management of hypercalcemia after renal transplantation. AB - Post-transplant hypercalcemia due to persistent secondary hyperparathyroidism (HPT) has a high prevalence in the first 3 months after surgery and decreases during the first year, but it persists over time in around 5-10% of renal transplant patients. The increased bone resorption and tubular reabsorption of calcium due to the action of the parathyroid hormone (PTH) appear to be the main mechanisms involved in hypercalcemia. At the time of the renal transplantation (RT), PTH is the factor that determines the development of post-RT hypercalcemia, although it is sometimes masked in patients who are well controlled with medical treatment. The number of dialysis patients receiving treatment with cinacalcet for secondary HPT is increasing. The withdrawal of the calcimimetic at the time of renal transplantation results in a higher prevalence of hypercalcaemia and hyperparathyroidism in these patients. In patients with PTH well controlled with cinacalcet before transplantation, there is a direct relationship between the dose and the subsequent development of hypercalcemia, probably because it indicates the presence of a more severe secondary HPT. Hypercalcemia may have deleterious effects on the renal graft, resulting in tubulointerstitial calcification. Persistent hypercalcemia is a marker of an increased risk of bone disease deterioration in these patients. Nowadays, the first treatment option is cinacalcet and if there is no response, we consider performing a parathyroidectomy. In this review, we propose an algorithm for management of post RT hypercalcemia. PMID- 24241362 TI - Thoughts on the start and withdrawal of dialysis. AB - Increased life expectancy and the availability of treatments provided by modern medicine have given rise to a new situation in which survival may be prolonged without the patient having an acceptable quality of life. Renal replacement therapy (RRT) to treat End Stage Renal Disease (ESRD) may involve the use of aggressive techniques designed to improve and prolong the lives of patients with high comorbidity and very low short term survival expectancy. RRT often means lowering patients’ quality of life, it is a significant burden on families and survival expectancy is low. Patients must actively participate in decision making, but to do so, the information about the prognosis of their disease and how the treatment will affect their quality of life must be more comprehensive. As nephrologists, we will be able to contribute better to decision-making by improving prognostic tools and participating collectively with the patient and their family in the final decision. It is necessary to offer appropriate care to patients who opt for conservative treatment by implementing multidisciplinary teams within ESRD units. PMID- 24241363 TI - Oral colonisation and infection by Candida sp. in diabetic and non-diabetic patients with chronic kidney disease on dialysis. AB - INTRODUCTION: Oral candidiasis (OC) is a common opportunistic infection in immunocompromised patients. Species identification is sometimes important for treatment. objective: to determine the prevalence of different Candida species colonising or infecting the oral mucosa (OM) of diabetic (DM) and non-diabetic (non-DM) chronic kidney disease patients, comparing both groups and exploring potential risk factors. METHODS: 56 DM and 80 non-DM patients on chronic dialysis were examined. OM swabs were cultured on Sabouraud dextrose agar plates. Candida species were identified with API(r) galleries. OC was confirmed by exfoliative cytology. Statistical associations were analysed using chi2, Fisher's exact test (ET), and multiple logistic regression. RESULTS: Candida prevalence was 43.4%: 53.6% DM and 36.3% non-DM, (p=.045). The species identified were C. albicans 74.6%, C. glabrata 22.0%, C. tropicalis 15.2%, C. parapsilosis 3.4 %, C. kefyr 3.4% and C. famata 1.7% without difference between groups. DM patients had a higher xerostomia prevalence (p=.002) and lower salivary flow (p=.008) and lower serum albumin (p=.018). 16.9% of patients had OC, 23.2% DM compared with 12.5% non-DM, (p=.101). The following were associated with the presence of Candida in the OM: the use of dental prostheses (odds ratio [OR] 25.6, 95% confidence interval [CI] 2.5 to 253, P=.001), xerostomia (OR 9.6, 95% CI 2.4 to 38.1, P=.001) and low serum albumin values (OR 0.41, 95% CI 0.22 to 0.98, P=.044). CONCLUSIONS: The presence of Candida sp. in the OM was associated with dental prostheses, xerostomia and low serum albumin. PMID- 24241364 TI - The influence of renin-angiotensin system genotypes on the antiproteinuric response to high doses of olmesartan in non-diabetic proteinuric nephropathies. AB - OBJECTIVE: To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C. MATERIAL AND METHOD: We studied 53 patients with non-diabetic proteinuric nephropathy with a mean progression time of 84.4+/ 15 months. 41 were males (77.4%); mean age 49.7+/-3 years, body mass index 30+/ 6kg/m2. All received olmesartan (40mg/12h) associated with a mean of 2.4+/-1.6 antihypertensive drugs for a median period of 13 months (interquartile range 7-25 months). RESULTS: Systolic blood pressure (BP) decreased from 145+/-14mmHg to 128+/-14mmHg (P<.001) and diastolic BP from 85+/-11mmHg to 79+/-7mmHg (P<.01). Pulse pressure decreased from 53.5+/-14mmHg to 48+/-12mmHg (P<.05). Proteinuria decreased from 2.74+/-1.6g/24h to 0.9+/-1g/24h (P<.001), representing a mean decrease of 67.1%. According to RAS polymorphisms, antiproteinuric response was: angiotensinogen gene polymorphism: genotype TT: 76.8%; genotype MM: 67.3%; genotype MT: 65.8%, significantly higher (P<.05) for genotype TT compared to genotypes MM and MT. Polymorphism of the ACE gene: genotype DD: 71.4%; genotype ID: 60.6%, genotype II: 34.8%, significantly higher (P<.05) for genotype DD compared to genotypes ID and II, and also (P<.05) for genotype ID compared to II. AT1R gene polymorphism: genotype AC: 85.2%; genotype CC: 73.7%; genotype AA: 62.7%; significantly higher for genotype AC (P<.05) compared to genotypes AA and CC. The differences between initial and final proteinuria for the follow-up period were significant (P<.01) for genotypic associations DD/AA, DD/MT, DD/MM, DD/TT and DD/AC, although the association with the highest antiproteinuric effect was DD/AC (89.9%, P<.05%). CONCLUSIONS: Administering high doses of olmesartan in patients with non-diabetic proteinuric nephropathy results in significant reductions in proteinuria. This decrease was independent of blood pressure control and other confounding factors. RAS polymorphisms may modulate the antiproteinuric response to treatment with ARBs. PMID- 24241365 TI - A comparison of the effectiveness of two online haemodiafiltration modalities: mixed versus post-dilution. AB - INTRODUCTION: Haemodiafiltration (HDF) with high reinfusion volumes is the most effective technique for clearing uraemic toxins. There are various modalities depending on the location where the replacement volume is administered in the extracorporeal circuit: pre-dilution, mixed or mid-dilution and post-dilution, in which the infusion is carried out pre-dilution, pre- and post-dilution simultaneously and post-dilution, respectively. OBJECTIVE: Compare the clearance of small, medium-sized and protein-bound molecules and the convective volume administered in online HDF (OL-HDF) in post-dilution and mixed (pre-post dilution) infusion. MATERIAL AND METHOD: A prospective, randomised, crossover study comparing post-dilution and mixed OL-HDF. Patients (n=8) were randomly assigned to receive 6 sessions in each technique. We conducted 89 sessions, of which 68 were at a scheduled time (ST) and 21 at an effective time (ET). We determined the reduction rate (RR) percentages for various substances and the infusion volumes. The RR study was performed using ET. RESULTS: The KT value obtained was greater with post-dilution OL-HDF [68 (8.1) compared to 64.9 (8.8) litres] (P=.009) when patients were dialysed at ST. This difference disappeared when dialysis was performed at ET. The difference between ST and ET was greater in mixed HDF than in post-dilution HDF [10.3 (7.4) compared to 6.5 (3.1) minutes, P=.02]. We found no differences in the RR of the substances analysed. CONCLUSION: Mixed OL-HDF is not inferior to post-dilution OL-HDF either in the clearance of small and medium-sized molecules or in the clearance of protein-bound molecules at the same ET. PMID- 24241366 TI - Effectiveness of haemodiafiltration with ultrafiltrate regeneration in the reduction of light chains in multiple myeloma with renal failure. AB - Acute kidney failure in multiple myeloma (MM) occurs in 12%-20% of patients and is a poor prognostic factor for patient survival. Recent studies have shown that dialysis with a High-Cut-Off membrane (HCO) removes free light chains (FLC) effectively although with significant albumin loss. Other adsorption-based techniques, such as haemodiafiltration with ultrafiltrate regeneration by adsorption in resin (SUPRA-HFR), have not been studied. We present three cases of MM, all haemodialysis-dependent since diagnosis. Two cases were IgG kappa and one was IgA lambda. All patients were treated with chemotherapy and SUPRA-HFR. The aim of this study was to evaluate the effectiveness of SUPRA-HFR in the reduction of FLC and its effect on albumin. We collected blood samples pre- and post dialysis, and ultrafiltrate (UF) samples pre- and post-resin 5 minutes into the session and 5 minutes from the end. The mean reduction rate of FLC in blood per session in the three patients was 53% and 63% (kappa) and 38% (lambda). In the UF, the mean FLC reduction rate was close to 99%, both at the start and at the end of dialysis, without the removal of albumin. With the results obtained we can conclude that this technique achieves an effective reduction of FLC, which is maintained throughout the session, without resin saturation and without albumin loss. Therefore, SUPRA-HFR is effective as an adjunctive therapy for MM. PMID- 24241367 TI - The impact of processing meat and fish products on phosphorus intake in chronic kidney disease patients. AB - INTRODUCTION AND OBJECTIVES: The use of phosphate additives in meat and fish processing leads to a phosphorus overload that we cannot quantify through labelling or food composition tables. We analysed this increase by measuring phosphorus content in these products by spectrophotometry. MATERIALS AND METHOD: We determined the phosphorus/protein ratio in fresh meat and fish products with varying degrees of processing by spectrophotometry (phosphorus) and the Kjeldahl method (proteins). We contrasted these results with those reflected in the food composition tables. RESULTS: The phosphorus/protein ratio was higher in processed meat products (15.83 mg/g) than in battered (11.04 mg/g) and frozen meat products (10.5mg/g), and was lower in fresh (8.41 mg/g) and refrigerated meat products (8.78 mg/g). Fresh white fish had a phosphorus/protein ratio of 8.58mg/g, while it increased by 22% (10.3mg/g) in frozen white fish and by 46% (12.54 mg/g) in battered fish. The information in the tables was poor and confusing, and no reference is made to the brands tested. CONCLUSIONS: Processing meat and fish products poses a serious obstacle to the reduction of phosphorus intake. The current regulatory framework does not assist us in the objective of reducing phosphorus additives, since it considers them safe for public consumption. Overcoming these barriers requires a coordinated effort to demonstrate that a high intake of these additives may be harmful to the general population and it should be more closely examined by regulators. PMID- 24241368 TI - Sodium set-point in haemodialysis: is it what we see clinically? AB - BACKGROUND: Natraemia in haemodialysis (HD) patients is considered constant contrary to daily clinical observations. Its relationship with clinical parameters, dialysis parameters and body water (BW) distribution is not clear. OBJECTIVES: The aims of this study were to know 1) the intraindividual variability of natraemia, 2) the relationship between natraemia and clinical and dialysis parameters and 3) the relationship between natraemia and BW distribution by bioimpedance. MATERIAL AND METHOD: Observational retrospective study on 98 chronic HD patients. Clinical, HD and natraemia, glucose and bioimpedance data were collected. RESULTS: We included 63 males and 35 females of 69.6 (21-91) years of age, with a follow-up of 23.2 (10) months. Variability: 1802 sodium measurements: mean natraemia 138 (3.2) mEq/l and corrected for glucose: 139.1 (3.6) mEq/l, p<.0001. Intraindividual coefficient of variation (CV) was 2% (0.8) (range 1-5.6%) and it correlated negatively with natraemia (r=-0.63, p<.0001). Clinical parameters: corrected natraemia was lower in diabetics than in non diabetics 138 (2.4) compared with 139 (2) mEq/l, p<.003, CV 2.3 (0.9) compared with 1.9 (0.7)% (p<.01) and SD 3.2 (1.2) compared with 2.5 (0.9) mEq/l (p<.04). No differences according to gender, age, HD time, cardiac or liver disease, medication use, residual renal function or mortality were found. HD parameters: a positive relationship was found between natraemia and total dialysate conductivity and it was negative with interdialysis weight gain (IDG). - Bioimpedance: no relationship was found between natraemia and BW distribution. CONCLUSIONS: Natraemia varies in each patient and is related positively with conductivity and negatively with IDG. In diabetics natraemia is lower and CV is higher. There is no relationship between natraemia and BW distribution. PMID- 24241369 TI - The influence of emotional factors on the report of somatic symptoms in patients on chronic haemodialysis: the importance of anxiety. AB - OBJECTIVE: To evaluate the prevalence of different somatic symptoms in chronic haemodialysis patients compared with a control group and to analyse the predictive capacity of some psychological variables (namely anxiety, depression, social support, self-efficacy and coping strategies) in the reporting of these symptoms. METHOD: Forty-six patients undergoing dialysis treatment and 30 individuals without relevant illness, matched in socio-demographic variables, were evaluated with self-reported measures. Relationships between somatic symptoms and predictor variables were analysed through bivariate correlations and multiple regression analysis. RESULTS: Patients showed much higher somatic symptom values than control individuals, especially with regard to immunological, cardiovascular, gastrointestinal and skin-allergy symptoms. Anxiety, with a positive association, was the main independent predictor in most of the symptom categories, explaining 24.9% (p<.0001) of variance in the total number of reported symptoms. Depression, the degree of worry, and passive coping strategies (helplessness-despair and fatalism) were also associated with higher levels of somatic symptoms. By contrast, the active coping strategy of fighting spirit, self-efficacy (coping capacity) and social support were associated with lower levels of symptoms. CONCLUSIONS: These results have clinical implications with respect to the aspects on which psychological interventions intended to reduce somatic symptoms in chronic haemodialysis patients should be based and they suggest that psychological-emotional variables may explain some symptoms that do not have a clear aetiology in kidney patients. PMID- 24241370 TI - Renal cortical necrosis secondary to thrombotic microangiopathy in the context of acute promyelocytic leukaemia blast crisis. AB - A 37-year-old patient was transferred to Haematology from the ENT Emergency Department where he had been admitted due to tonsillitis. He displayed anaemia and leukopenia and had agranulocytosis in the study. A day later the patient had blast crisis, and was diagnosed with myeloid acute leukaemia. Due to blast crisis the patient experienced sudden back pain, with oliguria and renal function deterioration followed by anaemia, in the context of haemolysis consistent with thrombotic microangiopathy, and as such, we were consulted. We began treatment with plasmapheresis and on the following day we performed haemodialysis (we carried out a total of 12 sessions of plasmapheresis until haemolysis disappeared). Five days later there was respiratory failure, and the patient was consequently transferred to the Intensive Care Unit, where he continued treatment with plasmapheresis and haemodialysis. The patient remained anuric thereafter, requiring haemodialysis, with no sign of renal recovery. Once platelet levels normalised with haematology chemotherapy, a percutaneous renal biopsy was performed, which confirmed the diagnosis of cortical necrosis. Finally, the patient underwent renal replacement therapy by regular haemodialysis. PMID- 24241371 TI - Comment on "Magnesium and chronic kidney disease". PMID- 24241372 TI - Response to the comment on "Magnesium and chronic kidney disease". PMID- 24241373 TI - Comment on "Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome". PMID- 24241374 TI - Response to the comment on "Cardiac troponin I and creatine kinase MB isoenzyme in patients with chronic renal failure". PMID- 24241375 TI - Comment on "Cardiac troponin I and creatine kinase MB isoenzyme in patients with chronic renal failure". AB - Comment on: Nefrologia 2012;32(6):809-18. PMID:23169364 [PubMed - in process]. PMID- 24241376 TI - Immunoglobulin A nephropathy could be a clue for the recurrence of gastric adenocarcinoma. PMID- 24241377 TI - The E23K polymorphism of the KCNJ11gene is associated with lower insulin release in patients with autosomal dominant polycystic kidney disease. PMID- 24241378 TI - Effect of allopurinol on smoking. PMID- 24241379 TI - Nephrocalcinosis and distal renal tubular acidosis in Sjogren's syndrome. PMID- 24241380 TI - Kaposi's sarcoma in the early post-transplant period in a kidney transplant recipient. PMID- 24241382 TI - Dabigatran-induced upper intestinal bleeding in a patient with chronic kidney disease. PMID- 24241381 TI - Myeloma kidney: the importance of assessing the response by monitoring free light chains in serum. PMID- 24241383 TI - Painful gynaecomastia secondary to cyclosporine A and tacrolimus in a patient with focal segmental glomerulosclerosis. PMID- 24241386 TI - Rotationplasty as a salvage of failed primary limb reconstruction: up to date review and case report. AB - We report a case of a 15-year-old girl who is a known case for proximal focal femoral deficiency. She underwent several surgical lengthening procedures. Her course was complicated by femur nonunion, knee joint dislocation, stiff knee, and final lower limb discrepancy of over 15 cm. Rotationplasty was performed to salvage her previous surgical failures and restore her function. Surgery was uneventful and the patient was able to walk with the prosthesis in a few months after index surgery. Although the outcome of rotationplasty is visually unusual, for some children restored function and physical capabilities outweigh cosmetic concerns. The aim of the present study was to report a case of rotationplasty in salvaging a failed primary limb reconstruction in a patient with proximal femur focal deficiency. PMID- 24241385 TI - Detection of QTL in rainbow trout affecting survival when challenged with Flavobacterium psychrophilum. AB - Bacterial cold water disease (BCWD) causes significant economic loss in salmonid aquaculture. We previously detected genetic variation in survival following challenge with Flavobacterium psychrophilum (Fp), the causative agent of BCWD in rainbow trout (Oncorhynchus mykiss). A family-based selection program to improve resistance was initiated in 2005 at the USDA National Center for Cool and Cold Water Aquaculture. Select crosses were made in 2007 and 2009 to evaluate family based disease survival using Fp injection challenges. From each putative F2/BC1 family generated in 2009, 200-260 fish were challenged in 4-7 replicates per family. Whole genome QTL scans of three F2/BC1 families were conducted with about 270 informative microsatellite loci per family spaced at an average interval size of 6 cM throughout the rainbow trout genome. Markers on chromosomes containing QTL were further evaluated in three additional F2/BC1 families. The additional F2/BC1 families were sire or dam half-sibs (HS) of the initially genome scanned families. Overall, we identified nine major QTL on seven chromosomes that were significant or highly significant with moderate to large effects of at least 13 % of the total phenotypic variance. The largest effect QTL for BCWD resistance explaining up to 40 % of the phenotypic variance was detected on chromosome OMY8 in family 2009070 and in the combined dam HS family 2009069-070. The nine major QTL identified in this study are candidates for fine mapping to identify new markers that are tightly linked to disease resistance loci for using in marker assisted selection strategies. PMID- 24241387 TI - Effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation. AB - Prone ventilation is an effective method for improving oxygenation in patients with acute respiratory failure. However, in extracorporeal circulation, there is a risk of cannula-related complications when changing the position. In this study, we investigated cannula-related complications when changing position for prone ventilation and the effect of prone ventilation on impaired oxygenation in patients who underwent extracorporeal membrane oxygenation (ECMO). The study subjects were patients who underwent prone ventilation during ECMO in the period from 2004 to 2011. Indication for prone ventilation was the presence of dorsal infiltration shown by lung computed tomography. Factors investigated were cannula insertion site, dislodgement or obstruction of the cannula, malfunction of vascular access and unplanned dislodgement of the catheters when changing position. Mean arterial pressure, PaO2/FiO2, PEEP level, blood flow and rotation speed of the pump were also determined before and after position change. Five patients were selected as study subjects. The mean duration of prone positioning was 15.3 +/- 0.5 h. Strict management during position changes prevented cannula related complications in the patients who underwent extracorporeal circulation. There were no significant changes in mean arterial pressure, PEEP level, blood flow and rotation speed of the pump when changing position. Low PaO2/FiO2 prior to prone ventilation was significantly increased after supine to prone and then prone to supine position. Prone positioning to improve impaired oxygenation is a safe procedure and not a contraindication in patients receiving extracorporeal circulation. PMID- 24241388 TI - Electron microscopic study of succession in the periphyton community of lake Washington. AB - Microbial succession has been observed on electron microscope grids immersed in lake water for 1, 3, 6, and 10 days. As predicted by ecological theory, the biomass, numbers, and diversity of attached microorganisms increased as succession proceeded. The diversity index of Shannon showed a marked increase from 3.1 at day 1 to 4.2 at day 3. It continued to rise at day 6 and attained the maximum value calculated on day 10 of 4.8. Bacteria were the major pioneer colonizers in this mesotrophic community. Based on these results and the results of other microbiologists who have found bacteria to be the dominant component during the pioneer stage of succession in periphyton communities of varying trophic status, we suggest that microbial heterotrophs may commonly, and perhaps always, be the major component of the early pioneer community of autogenic successions. PMID- 24241389 TI - Autoradiographic screening for potential heterotrophs in natural algal populations of Lake Kinneret. AB - Microautoradiography was used to screen natural phytoplankton populations from Lake Kinneret for their ability to take up radioactive organic substrates (glucose, acetic acid, amino acids, and glycollic acid. Several of the important Chlorophyta (Pediastrum spp.,Actinastrum hantzschii, Kirchncriella spp.,Coelastrum spp.,Scenedesmus spp., andTetraedron spp.) and Cyanophyta (Microcystis spp.,Merismopedia sp.,Chroococcus spp., andAnabaena spp.) showed consistent organic uptake. However, the principal bloom former, the dinoflagellatePeridinium cinctum fawestii and most of the pelagic algae observed, never assimilated any of the above substrates. Autoradiographic surveys permit rapid screening of algal populations for species which are capable of taking up organic matter and can indicate potential facultative heterotrophs. PMID- 24241390 TI - On describing microbial growth kinetics from continuous culture data: Some general considerations, observations, and concepts. AB - Analysis of continuous culture methodology suggests that this potentially powerful tool for kinetic analysis can be improved by minimizing several inherent shortcomings. Medium background substrates - organic carbon, phosphate, and manganese - were shown to dominate kinetic observations at concentrations below chemical detection methods. Reactor wall growth, culture size distribution changes, sample removal-induced steady state perturbations, and limiting substrate leakage from organisms are treated in terms of kinetic measurement errors. Large variations in maximal growth rates and substrate uptake rates found are attributed to experimental protocol-induced transient states. Relationships are presented for correcting limiting substrate concentrations for lability during sampling, contamination with unreacted medium, and background substrate effects. Analytical procedures are discussed for improved measurement of limiting substrate kinetics involving enzymes, isotopes, and material balance manipulation. Relaxation methods as applied to continuous culture are introduced as a means for isolating separate rate constants describing net substrate transport and for evaluating cellular metabolite leakage. Low velocity growth, multiple substrate metabolism, and endogenous metabolism are discussed along with measurements showing that 1-month generation times for aquatic microorganisms can be quite normal and that the kinetics are compatible withMUg/liter limiting substrate concentrations. The concept of regarding growth kinetics as the sum of several net accumulation processes is suggested. PMID- 24241391 TI - Properties of marine bdellovibrios. AB - Marine bdellovibrio isolates from the Israeli littoral of the Mediterranean Sea were screened and characterized in terms of host range, temperature and salinity ranges, cation requirement, mutation frequency, and G + C% mole content. Ten types of isolates were distinguished on the basis of these parameters. PMID- 24241392 TI - Microorganisms from composting leaves: Ability to produce extracellular degradative enzymes. AB - Mixed populations of bacteria, fungi, and actinomycetes in a leaf compost pile were examined over a 100-day test period for their ability to produce extracellular proteolytic, lipolytic, amylolytic, cellulolytic, pectolytic, and ureolytic enzymes and ability to utilize alkanes. Urea was added to the leaves to adjust the carbon to nitrogen ratio but was of little value in maintaining the proper ratio since it was degraded within the first few days. The degradative enzymes excreted by microorganisms was dependent on the temperature of the pile. In many cases organisms able to produce specific extracellular enzymes at medium temperatures were able to grow at high temperatures, but either did not excrete the specific enzymes or the enzymes were inactivated by the high temperature. PMID- 24241393 TI - The mission of the International Endotoxin and Innate Immunity Society. PMID- 24241394 TI - Distal connectivity causes summation and division across mouse visual cortex. AB - Neurons in different locations across the cortex are connected through polysynaptic networks involving both excitation and inhibition. To probe the functional effect of such networks, we used optogenetic stimulation to trigger antidromic spikes in a local region of primary visual cortex (V1). This local activity had two effects at distal V1 locations: summation and division. The balance between the two depended on visual contrast, and a normalization model precisely captured these effects. PMID- 24241395 TI - Female contact modulates male aggression via a sexually dimorphic GABAergic circuit in Drosophila. AB - Intraspecific male-male aggression, which is important for sexual selection, is regulated by environment, experience and internal states through largely undefined molecular and cellular mechanisms. To understand the basic neural pathway underlying the modulation of this innate behavior, we established a behavioral assay in Drosophila melanogaster and investigated the relationship between sexual experience and aggression. In the presence of mating partners, adult male flies exhibited elevated levels of aggression, which was largely suppressed by prior exposure to females via a sexually dimorphic neural mechanism. The suppression involved the ability of male flies to detect females by contact chemosensation through the pheromone-sensing ion channel ppk29 and was mediated by male-specific GABAergic neurons acting on the GABAA receptor RDL in target cells. Silencing or activating this circuit led to dis-inhibition or elimination of sex-related aggression, respectively. We propose that the GABAergic inhibition represents a critical cellular mechanism that enables prior experience to modulate aggression. PMID- 24241396 TI - Auto-attraction of neural precursors and their neuronal progeny impairs neuronal migration. AB - Limited neuronal migration into host brain tissue is a key challenge in neural transplantation. We found that one important mechanism underlying this phenomenon is an intrinsic chemotactic interaction between the grafted neural precursor cells (NPCs) and their neuronal progeny. NPCs secrete the receptor tyrosine kinase ligands FGF2 and VEGF, which act as chemoattractants for neurons. Interference with these signaling pathways resulted in enhanced migration of human neurons from neural clusters. PMID- 24241397 TI - Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety. AB - Successfully differentiating safety from danger is an essential skill for survival. While decreased activity in the medial prefrontal cortex (mPFC) is associated with fear generalization in animals and humans, the circuit-level mechanisms used by the mPFC to discern safety are not clear. To answer this question, we recorded activity in the mPFC, basolateral amygdala (BLA) and dorsal and ventral hippocampus in mice during exposure to learned (differential fear conditioning) and innate (open field) anxiety. We found increased synchrony between the mPFC and BLA in the theta frequency range (4-12 Hz) only in animals that differentiated between averseness and safety. Moreover, during recognized safety across learned and innate protocols, BLA firing became entrained to theta input from the mPFC. These data suggest that selective tuning of BLA firing to mPFC input provides a safety-signaling mechanism whereby the mPFC taps into the microcircuitry of the amygdala to diminish fear. PMID- 24241398 TI - Possible role of gap junction intercellular channels and connexin 43 in satellite glial cells (SGCs) for preservation of human spiral ganglion neurons : A comparative study with clinical implications. AB - Human spiral ganglion (SG) neurons show remarkable survival properties and maintain electric excitability for a long time after complete deafness and even separation from the organ of Corti, features essential for cochlear implantation. Here, we analyze and compare the localization and distribution of gap junction (GJ) intercellular channels and connexin 43 (Cx43) in cells surrounding SG cell bodies in man and guinea pig by using transmission electron microscopy and confocal immunohistochemistry. GJs and Cx43 expression has been recognized in satellite glial cells (SGCs) in non-myelinating sensory ganglia including the human SG. In man, SG neurons can survive as mono-polar or "amputated" cells with unbroken central projections following dendrite degeneration and consolidation of the dendrite pole. Cx43-mediated GJ signaling between SGCs is believed to play a key role in this "healing" process and could explain the unique preservation of human SG neurons and the persistence of cochlear implant function. PMID- 24241399 TI - Association between decreasing trend in the mortality of adult T-cell leukemia/lymphoma and allogeneic hematopoietic stem cell transplants in Japan: analysis of Japanese vital statistics and Japan Society for Hematopoietic Cell Transplantation (JSHCT). AB - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with a very poor outcome. However, several studies have shown a progress in the treatment. To evaluate the effect of the progress in the treatment of ATLL in a whole patient population, we used vital statistics data and estimated age-adjusted mortality and trends in the mortality from 1995 to 2009. Since allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has been introduced as a modality with curative potential during study period, we also evaluated the association of the annual number of allo-HSCT and the trend of the mortality of ATLL. Endemic (Kyushu) and non-endemic areas (others) were evaluated separately. Significance in the trend of mortality was evaluated by joinpoint regression analysis. During the study period, a total of 14 932 patients died of ATLL in Japan, and mortality decreased significantly in both areas (annual percent change (95% confidence interval (CI)): Kyushu, -3.1% (-4.3, -1.9); others, -3.4% (-5.3, -1.5)). This decreasing trend in mortality seems to be associated with an increase in the number of allo-HSCTs (Kyushu, R-squared=0.70, P=0.003; and others, R squared=0.55, P=0.058). This study reveals that the mortality of ATLL is now significantly decreasing in Japan and this decreasing trend might be associated with allo-HSCT. PMID- 24241400 TI - Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia. AB - To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59-100%) and a specificity of 87% (CI 70-96%). Positive and negative predictive values were 71% (CI 42-92%) and 96% (CI 82-100%), respectively. In conclusion, flow cytometric p STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria. PMID- 24241402 TI - Alternative final steps in berberine biosynthesis in Coptis japonica cell cultures. AB - In Coptis japonica cell cultures an alternative pathway has been discovered which leads from (S)-tetrahydrocolumbamine via (S)-canadine to berberine. The two enzymes involved have been partially purified. (S)-Tetrahydrocolumbamine is stereospecifically transformed into (S)-canadine under formation of the methylenedioxy bridge in ring A. This new enzyme was named (S)-canadine synthase. (S)-Canadine in turn is stereospecifically dehydrogenated to berberine by an oxidase, (S)-canadine oxidase (COX), which was partially purified (25-fold). This enzyme has many physical properties in common with the already known (S) tetrahydroprotoberberine oxidase from Berberis but grossly differs from the latter enzyme in its cofactor requirement (Fe) and its substrate specificity. Neither (S)-norreticuline nor (S)-scoulerine serves as substrate for the Coptis enzyme, while both substrates are readily oxidized by the Berberis enzyme. The four terminal enzymes catalyzing the pathway from (S)-reticuline to berberine are housed in Berberis as well as in Coptis in smooth vesicles with a density of rho=1.14 g/ml. These vesicles have been enriched and characterized by electron microscopy. PMID- 24241401 TI - SWR/J mice are susceptible to alkylator-induced myeloid leukemia. PMID- 24241403 TI - Intergeneric somatic hybrid plants of Citrus sinensis cv. Hamlin and Poncirus trifoliata cv. Flying Dragon. AB - Intergeneric somatic hybrid plants between 'Hamlin' sweet orange [Citrus sinensis (L.) Osbeck] and 'Flying Dragon' trifoliate orange (Poncirus trifoliata Raf.) were regenerated following protoplast fusion. 'Hamlin' protoplasts, isolated from an habituated embryogenic suspension culture, were fused chemically with 'Flying Dragon' protoplasts isolated from juvenile leaf tissue. The hybrid selection scheme was based on complementation of the regenerative ability of the 'Hamlin' protoplasts with the subsequent expression of the trifoliate leaf character of 'Flying Dragon.' Hybrid plants were regenerated via somatic embryogenesis and multiplied organogenically. Hybrid morphology was intermediate to that of the parents. Chromosome counts indicated that the hybrids were allotetraploids (2n=4x=36). Malate dehydrogenase (MDH) isozyme patterns confirmed the hybrid nature of the regenerated plants. These genetically unique somatic hybrid plants will be evaluated for citrus rootstock potential. The cell fusion, selection, and regeneration scheme developed herein should provide a general means to expand the germplasm base of cultivated Citrus by intergeneric hybridization with related sexually incompatible genera. PMID- 24241404 TI - Establishment of new axenic hairy root lines by inoculation with Agrobacterium rhizogenes. AB - Cultured hairy root lines resulting from infection by Agrobacterium rhizogenes are known for approximately thirty plant species. We extend this range by establishing forty original dicotyledonous hairy root lines with A. rhizogenes strain A4. Hairy roots have been cultured for at least 2-6 years on Murashige & Skoog medium. Some hairy root cultures such as Anagallis arvensis and Antirrhinum majus spontaneously regenerated whole plants. PMID- 24241405 TI - A rapid transformation method for Solanum tuberosum using binary Agrobacterium tumefaciens vectors. AB - A tuber disc transformation and regeneration system was devised for potato (Solanum tuberosum). Tuber discs were found to be the most morphogenetic organ on a medium previously optimised for tomato regeneration. Shoot regeneration from tuber discs was rapid and transformed as shown by nopaline assays and Southern blot analysis. The ease and speed of the tuber disc method will allow for the increased use of this commercially important plant in transformation studies. PMID- 24241406 TI - Intraspecific gametosomatic hybridisation in Petunia hybrida. AB - Following PEG and high pH induced fusion of haploid tetrad protoplasts of a normal purple flowered variety of P. hybrida with cell suspension protoplasts of a nuclear albino mutant of the variety Blue Lace, triploid gametosomatic hybrid plants were recovered. These hybrids possessed an intermediate floral morphology and the expected chromosome number of 2n=3x=21. Selection was based on the fact that pollen tetrad protoplasts failed to divide in culture and that, following complementation to chlorophyll proficiency in the gametosomatic hybrid, the hybrid cells were visualised against a background of albino cells of the variety Blue Lace. The production of such gametosomatic hybrid plants in Petunia has shown that the concept of gametosomatic hybridisation can be extended to genera other than Nicotiana and that alternative selection strategies are available. PMID- 24241407 TI - Common responses of cultured soybean cells to 2,4-D starvation and fungal elicitor treatment. AB - The patterns of in vivo protein synthesis in soybean cell suspensions were compared by polyacrylamide gel electrophoresis after the cells had been submitted to different stress conditions : treatment with Phytophthora megasperma (Pmg) cell wall elicitors, 2,4-D starvation and heat shock (HS) temperatures. Changes in protein synthesis patterns induced after elicitation of cell suspensions or after infection of soybean hypocotyls by Pmg were found to be similar to changes brought about by auxin starvation of the cells. Changes common to both stress situations involve a prominent 17 kDa peptide family and 27, 29, 35 and about 45 kDa peptides. Moreover, "defense" reactions, i.e. glyceollin accumulation and synthesis of chalcone synthase (CHS) were also strongly stimulated in auxin starved cells. On the contrary, although characteristic sets of low molecular weight heat shock (HS) proteins were synthesized by cells grown at 37 degrees C, no clear similarity was observed with peptides characteristic of auxin-starved cells. PMID- 24241408 TI - Plant regeneration via somatic embryogenesis in the seeded diploid banana Musa ornata Roxb. AB - Somatic embryos of a seeded diploid ornamental banana (Musa ornata Roxb.) were obtained from zygotic embryos cultured on semi-solid Murashige and Skoog (MS) (1962) medium with the auxin 2,4-D (0.5, 1, 2 mg/l) and 5% CW. Removal of 2,4-D and transferral to Schenk and Hildebrandt (SH) (1972) salts with CW followed by basal MS led to embryo germination and growth. Plantlet production was obtained using filter paper bridges in liquid half-strength SH medium with 1% sucrose. The remarkable phenotypic fidelity of somatic embryos to that of zygotic embryos and the presence of a haustorium-like outgrowth on the somatic embryos is described. PMID- 24241409 TI - Alkaloid production in cell suspension cultures of Thalictrum flavum and T. dipterocarpum. AB - Both cell suspension cultures of Thalictrum flavum and T. dipterocarpum were found to produce berberine (0.3 and 0.4 g/l, respectively) as a main alkaloid. Berberine production in the latter was markedly stimulated by 1-naphthaleneacetic acid in combination with 6-benzylaminopurine, whereas it was rather suppressed by the same auxin in the former. T. flavum cultures accumulated berberine and columbamine in the cells without releasing them into medium. On the other hand, T. dipterocarpum cultures released berberine into medium during the logarithmic growth phase, but thereafter accumulated all the berberine synthesized in the cells. PMID- 24241410 TI - An improved medium for adventitious shoot formation and callus induction in Beta vulgaris L. in vitro. AB - Six sugarbeet (Beta vulgaris L.) lines (GWI-248, SPB-11, MonoHy 55, SMS-1, EL45 and FC607) were tested for regeneration. Shoot cultures were initiated in vitro from naked, sterilized embryos obtained from mature seed. Excised petioles from cultured shoots were plated on Gamborg's B5 medium and four modified Murashige and Skoog (MS) media. A medium containing MS inorganic salts supplemented with 0.4 mg/1 N(6)-benzyladenine, 0.1 mg/1 indole-3-butyric acid, ten vitamins and six amino acids, termed RV, was superior for both adventitious shoot and callus formation. Callus was observed only on RV medium and only on petioles that did not develop adventitious buds directly. Rooting of regenerated shoots and development of complete plants was accomplished by transfer to Gamborg's B5 medium with 5 mg/l indole-3-butyric acid as the sole phytohormone. The complete process of regeneration through adventitious shoot production took from 4 to 6 weeks from explants to rooted plants. The callus that formed on nonorganogenic petioles was regenerative when transferred to fresh RV medium. Regeneration from callus occurred mainly by shoot organogenesis but also by somatic embryogenesis at a low frequency. PMID- 24241411 TI - Stimulation of chalcone synthase activity by yeast extract in cultured Glycyrrhiza echinata cells and 5-deoxyflavanone formation by isolated protoplasts. AB - Chalcone synthase activity catalyzing the formation of naringenin (5 hydroxyflavanone) was detected in cell suspension cultures of Glycyrrhiza echinata. This activity rapidly increased by treatment of the cells with yeast extract, while non-treated cells showed a constant low activity. Isolated G. echinata protoplasts accumulated retrochalcone (echinatin) and its biosynthetic intermediate (licodione) during 24 h of culture. When the protoplasts were incubated with [(14)C(U)]phenylalanine, liquiritigenin (5-deoxyflavanone) was transiently labeled, indicating the induction of 6'-deoxychalcone synthase. The formation of liquiritigenin, in addition to naringenin, was observed when the crude extracts from the protoplasts were assaved for CHS activity. PMID- 24241412 TI - In vitro propagation of Glehnia littoralis from shoot-tips. AB - Shoot cultures of Glehnia littoralis F. Schmidt ex Miq. (Umbelliferae) were established by placing shoot tip explants on Linsmaier and Skoog medium with 1 MUM NAA and 10 MUM BAP. Shoots were multiplied on the basal medium supplemented with 0.3 MUM NAA and 3 MUM BAP and rooted on medium containing either 1 MUM IBA or 3-10 MUM IAA. Plantlets survived in pots without any covering. This unique characteristic of the plantlets was ascribed partly to a well-developed cuticle on the surface of the leaf and the small ratio of surface area to fresh weight of a leaf blade in comparison with those of other species whose plantlets needed coverings after potting. The regenerated plantlets were finally transferred to soil. PMID- 24241413 TI - Partial purification and characterization of dihydrobenzophenanthridine oxidase from Eschscholtzia californica cell suspension cultures. AB - The observation that upon elicitation cell suspension cultures of Eschscholtzia california showed a decrease of dihydromacarpine with a concomittant increase of macarpine led to the discovery of a novel enzyme which catalyzes the oxidation of dihydrobenzophenanthridines in the presence of oxygen. The enzyme was enriched approx. 70-fold. It has a pH-optimum of 7.0, an isoelectric point at pH 8.8, molecular weight of 56 kD and shows a high degree of substrate specificity. The enzyme obviously catalyzes the terminal step in the formation of benzophenanthridine alkaloids containing methylene dioxy substitutions in rings A and D. PMID- 24241414 TI - Introduction of foreign genes into potato cultivars Bintje and Desiree using an Agrobacterium tumefaciens binary vector. AB - Tuber discs of Solanum tuberosum cv Bintje and Desiree were cocultivated with an Agrobacterium tumefaciens binary vector, carrying both the neomycine phosphotransferase and the E. coli beta-glucuronidase gene fused to resp. the nopaline synthase and Cauliflower mosaic virus 35S promotor.Inoculated tuber discs produce transgenic shoots in selective media containing kanamycin. The transgenic plants are phenotypically normal and contain the euploid number of chromosomes. Both the neomycin phosphotransferase as well as the beta glucuronidase gene are expressed conferring resp. kanamycin resistance and beta glucuronidase activity to the plants. PMID- 24241415 TI - Induction of triterpene biosynthesis by elicitors in suspension cultures of Tabernaemontana species. AB - Treatment of suspension cultures of some Tabernaemontana species (Apocynaceae) with elicitors (e.g. cellulase, Candida albicans) result in a rapid de novo production of antimicrobial active triterpenes. The triterpenes are identified as ursene carboxylic acid derivatives. These triterpenes are not produced by an elicited cell suspension culture of Catharanthus roseus, another Apocynaceae. PMID- 24241416 TI - A novel method for increasing the frequency of somatic embryogenesis in wheat tissue culture by NaCl and KCl supplementation. AB - The effect of NaCl, KCl and LiCl on the growth and morphogeneis of tissue cultures originating from immature embryos of four wheat (Triticum aestivum L.) and one triticale (Triticosecale)varieties was investigated. The morphogenetic pathway to plant regeneration in Chinese Spring wheat was determined as incomplete somatic embryogenesis because the differentiation and subsequent germination of the shoot apices happened in the early phase of embryo development. Culture medium supplemented by NaCl suppressed the differentiation of shoot apices resulting in the development of more typical somatic embryoids. Forty mM concentrations of both NaCl or KCl increased the formation of somatic embryos in Chinese Spring. Arthur and GK Kincso wheat varieties while Lasko triticale regenerated well without the addition. The salts inhibited plantlet formation from somatic embryoids so the salts supplement should be omitted. Forty mM LiCl inhibited growth while 10mM LiCl had no effect on growth or embryogenesis. PMID- 24241417 TI - Recovery of plants from leaf protoplasts of hybrid-poplar and aspen clones. AB - Leaf protoplasts were isolated from shoot cultures of two hybrid poplar clones (Populus alba * P. grandidentata 'Crandon', NC-5339 and P. nigra 'Betulifolia' * P. trichocarpa, NC-5331) and the Upright European Aspen (P. tremula 'Erecta') and were cultured in contact with screen discs floated in liquid medium. Protoplast culture was influenced by the growth medium of the source shoot cultures, the protoplast purification procedure, the plating density, and the presence or absence of a coconut water and casein hydrolysate supplement added to the culture medium. The protoplast-derived cells divided more quickly and with higher incidence than previously reported for hybrid poplars. Shoots were regenerated from the protoplast-derived calli and were maintained as shoot cultures. Plants were developed from microcuttings rooted ex vitro and were grown-on in the greenhouse and field. PMID- 24241418 TI - A negative selection scheme for tobacco protoplast-derived cells expressing the T DNA gene 2. AB - The amido hydrolase encoded by the T-DNA gene 2 catalyzes the conversion of indole-acetamide, alpha-naphthalene acetamide, and other substrate analogues into the corresponding auxins. As a result, only gene 2-expressing protoplast-derived tobacco cells can grow in medium containing low concentrations (0.2-1 MUM) of alpha-naphthalene acetamide as auxin precursor. However, in a mixture of SR1 and SR1, gene 2 (+) protoplast-derived cells, cross-feeding occurs and consequently no positive selection for gene 2 is obtained. A 100-times higher concentration of alpha-naphthalene acetamide (between 30 and 300 MUM) provides a negative selection scheme. Only the tobacco cells expressing gene 2 are sensitive to the high naphthalene acetamide concentration and cannot grow to colonies, while cells lacking the gene 2 product regenerate calli even in mixed gene 2 (+) and gene 2 ( ) cell populations. Thus, gene 2 might provide a unique biochemically defined marker to investigate mutations and gene inactivation. PMID- 24241419 TI - Culture of asparagus protoplasts on porous polypropylene membrane. AB - A method of using a buoyant porous polypropylene membrane floated on liquid medium to culture protoplasts of Asparagus officinalis L. is described. This method supports very good growth and eliminates the need to periodically replenish culture medium lost to evaporation. PMID- 24241420 TI - Somatic embryogenesis and organogenesis in callus cultures of a tree legume - Albizia richardiana King. AB - Hypocotyl explants of 1 and 10 mm lengths were excised from 12-day-old in vitro grown seedlings of Albizia richardiana. The larger pieces, after 40 days of culture, developed shoots along with green calli on B5 + BAP (10(-7)-10(-5)M), while the smaller segments produced only green calli on B5+BAP (10(-7)-10(-4)M) medium. Some of the green calli turned morphogenic and started producing somatic embryos with the 2nd sub-culture and shoots from 7th sub-culture onwards. Calli retained the morphogenic potential even after repeated sub-culturing for over two years. The number of embryos in an embryogenic culture varied from 2 to 20 per callus mass of 5-6.5 cm(3). Sucrose at the 2% level in MS medium was optimal for embryogenesis while 4% was optimal for shoot bud differentiation. Higher levels of sucrose (6-10%) caused browning of green calli and also inhibited differentiation into embryos and shoot buds. By selective sub-culturing of 0.1 cm(3) pieces of embryogenic calli on MS+10(-5)M BAP, 46% of the cultures produced somatic embryos. The latter germinated into plantlets on Knop's medium. PMID- 24241421 TI - Correlation between flow cytometric determination of nuclear DNA content and chromosome number in somatic hybrids within Brassicaceae. AB - Fourty-one somatic hybrids from two species combinations, Brassica oleracea + B. campestris and B. napus + Eruca sativa, were analysed for chromosome number and nuclear DNA content. The DNA content was measured in a flow cytometer using two internal standards as references and when related to the chromosome number a correlation of 0.91 was found. The chromosome number of the hybrids could be determined with an accuracy of +/-10% by using flow cytometry, and the smallest statistically significant difference in DNA content between two individuals was 0.23 pg DNA/cell. PMID- 24241422 TI - Anthocyanin and proteins as biochemical markers in maize endosperm cultures. AB - Endosperm maize cultures derived from a strain homozygous for all genes required for anthocyanin synthesis develop an intense pigmentation. Pigmenting ability is generally maintained in successive subcultures, altough colourless areas are frequently observed in pigmented cultures. The isolated colourless cell clusters show a growth rate higher than the coloured ones. These calli nevertheless do not lose the ability to synthesize anthocyanins, and in successive subcultures turn red again.The different growth rates associated with the ability of cells to accumulate pigments suggest the existence of different physiological states of the culture. To investigate this possibility we analyzed the polypeptide patterns of coloured and colourless cultures. SDS gel electrophoresis has demonstrated differences in soluble protein fractions, among which a 26 kD peptide, characteristic of pigmented tissues, has been evidenced. Zein, the major storage protein of maize endosperm is present, although at very low levels, both in pigmented and in unpigmented cultures, confirming that its synthesis occurs continuously in vitro. PMID- 24241423 TI - Studying Epstein-Barr virus pathologies and immune surveillance by reconstructing EBV infection in mice. AB - Epstein-Barr virus (EBV) is a gamma herpes virus endemic in humans and transforming human B lymphocytes. It causes a variety of human pathologies ranging from infectious mononucleosis upon acute infection to EBV-driven B-cell lymphomas. In humans, EBV-infected cells are under powerful immune surveillance by T and NK cells. If this immune surveillance is compromised as in immunosuppressed (AIDS- or posttransplantation) patients, the virus can spread from rare, EBV-containing cells and cause life-threatening pathologies. We have found that EBV immune surveillance and lymphomagenesis can be modeled in mice by targeted expression of key EBV proteins in the B-cell lineage. As EBV does not infect mouse B cells and mice have thus not coevolved with the virus, EBV exploits basic modes of the host immune response to optimize its coexistence with the host. PMID- 24241425 TI - Separation of mitochondria from microbodies of Pisum sativum (L. cv. Alaska) cotyledons. AB - A method is described for separating mitochondria from microbodies in cotyledon preparations of Pisum sativum L. cv. Alaska. Pure and intact mitochondria were obtained on a continuous: discontinuous sucrose density gradient as shown by marke-enzyme assay and electron microscopy. Manipulation of sucrose-gradient construction to widen the distance between organelles provided a quick method for the separation of the mitochondria from the microbodies. The shorter time of exposure of mitochondria to centrifugation and osmotic stress produces mitochondria free of contamination. PMID- 24241426 TI - Linamarase and other beta-glucosidases are present in the cell walls of Trifolium repens L. leaves. AB - Linamarase (EC 3.2.1.21) is a specialized beta-glucosidase that hydrolyses the cyanogenic glucoside linamarin. Two clones of Trifolium repens L. derived from natural populations, of which one clone exhibited linamarase activity, were used in a comparative study to try to establish the localization of linamarase and other beta-glucosidases. Two methods were used: the first one was vacuum infiltration of intact leaf cells, followed by centrifugation. A significant amount of linamarase and beta-glucosidase activity could be extracted from intact tissue by a 0.25 M NaCl solution, indicating that these activities are localized in the apoplast. The second method, immuno-cytofluorescense of microtome sections, confirmed this. It was found that linamarase and other beta glucosidases are present in the cell walls, especially those of the epidermal cells, and in the cuticle. However their presence in the cell walls of other tissues i.e. walls of the vessels, could not be excluded. No difference in distribution could be detected between linamarase and other beta-glucosidases. PMID- 24241427 TI - Lattice images from ultrathin sections of cellulose microfibrils in the cell wall of Valonia macrophysa Kutz. AB - The crystalline ultrastructure and orientation of cellulose microfibrils in the cell wall of Valonia macrophysa were investigated by means of high-resolution electron microscopy of ultrathin (approx. 28 nm) sections. With careful selection of imaging conditions, ultrastructural aspects of the cell wall that had remained unresolved in previous studies were worked out by direct imaging of crystal lattice of cellulose microfibrils. It was confirmed that each microfibril is a single crystal having a lateral dimension of 20.20 nm(2), because lattice images of 0.39 nm resolution were clearly recorded with no major disruption in the whole area of the cross section of the microfibril. There was no evidence for the existence of 3.5-nm elementary fibrils which have been considered to be basic crystallographic and morphological units of cellulose in general. It was also confirmed that the axial directions (crystallographic fiber direction) of adjacent microfibrils in each single lamella of the cell wall are opposite to each other. PMID- 24241428 TI - Immunofluorescence microscopy of microtubule arrangement in Closterium acerosum (Schrank) Ehrenberg. AB - The microtubule (MT) arrangement in Closterium acerosum cells was observed by indirect immunofluorescence microscopy both during and following cell division, and during cell expansion without cell division. (During the division period, some cells of this alga divide whereas other cells expand in their middle region without division.) Before septum formation, all cells had a ring-like MT bundle (MT ring) in their middle. Both septum formation and expansion without cell division occurred at the position of this ring. During the periods of division, short, hair-like MTs appeared around the nucleus in some of the cells, in addition to the MT ring. In dividing cells, spindle MTs appeared as the chromosomes were condensed. During the early stages of expansion of the semicells, after cell division, the spindle MTs assumed a radial arrangement, moved, and settled in a position between the daughter chloroplasts. These MTs disappeared about 1.5 h after septum formation. As the new semicells were growing, wall MTs appeared, arranged transversely along the expanding wall. These transverse MTs disappeared gradually 4-5 h after septum formation, and only an MT ring remained near the boundary between the new and old semicells. The MT ring was present until the next cell division or expansion without cell division. During the latter course of development, transverse wall MTs were present only at the band-like expanding region. At the earlier stage of expansion without cell division, the short, hair-like MTs remained around the nucleus, but as time passed, both the hair-like MTs and, somewhat later, the transverse ones disappeared and only the MT rings remained. The remaining MT ring was not always positioned at the boundary between the expanding and the old cell region. The temporal relationships between the changes in MT arrangement, and the orientation and localization of cellulose-microfibril deposition are discussed. PMID- 24241429 TI - In-vitro biosynthesis of 1-(4'-hydroxyphenyl)-2-nitroethane and production of cyanogenic compounds in osmotically stressed cell suspension cultures of Eschscholtzia californica Cham. AB - Cell suspension cultures of Eschscholtzia californica produce one or more cyanogenic compounds when placed under osmotic stress. The nature of the compound(s) has not yet been established but they are not identical with the cyanogenic glucosides triglochinin and dhurrin, which occur in the intact plant. Microsomal fractions isolated from stressed cell cultures catalyze the synthesis of 1-(4'-hydroxyphenyl)-2-nitroethane from L-tyrosine. Both NADPH and molecular oxygen are required as cosubstrates, and 4-hydroxyphenylacetaldoxime is an intermediate in the synthesis of the nitrocompound. This observation indicates that the biosynthetic pathways leading from L-tyrosine to 1-(4'-hydroxyphenyl)-2 nitroethane and to the L-tyrosine-derived cyanogenic glucosides are closely related. A glucosyltransferase which glucosylates the nitrocompound in the presence of uridine diphosphate glucose appears in the osmotically stressed cultures in a time pattern similar to that for production of the nitrocompound. PMID- 24241430 TI - Interaction between photosynthetic and respiratory electron-transfer chains in the membranes of Anabaena variabilis. AB - The rate of CO2- and p-benzoquione-dependent photosynthetic O2 evolution by Anabaena variabilis cells remained unaltered and the rate of O2 uptake observed after switching off the light (endogenous respiration) was enhanced by a factor of 6-8 when the O2 concentration was increased from 200 to 400 MUM. Photosystem-I linked O2 uptake and respiration of the cells incubated with ascorbate and N,N,N'N'-tetramethyl-p-phenylenediamine was not appreciable influenced by the O2 concentration. 2-Iodo-6-isopropyl-3-methyl-2',4,4'-trinitrodiphenyl ether, blocking electron transfer at the plastoquinone level, suppressed O2 evolution and had no influence on endogenous respiration. 2-n-Heptyl-4-hydroxyquinoline-N oxide, an inhibitor of electron transfer between photosystems II and I, as well as the cytochrome-oxidase inhibitors N 3 (-) , CN(-) and NH2OH, caused a 35-50% retardation of endogenous respiration and blocked photosynthetic O2 evolution. The molar ratio of cytochromes b6, f, c-553, aa3 and photosystem-I reaction centers in the isolated membranes equalled approx. 2:1:2:0.7:2. It is inferred that endogenous respiration of A. variabilis cells is inhibited by the light induced electron flow through both photosystems at the level of the plastoquinone plastocyanin-oxidoreductase complex. PMID- 24241431 TI - Bundle-sheath thylakoids from NADP-malic enzyme-type C4 plants require an exogenous electron donor for enzyme light activation. AB - Light activation of either NADP-malate dehydrogenase (EC 1.1.1.82) or fructose 1,6-bisphosphate phosphatase (EC 3.1.3.11) was assayed in a reconstituted chloroplastic, system comprising the isolated proteins of the ferredoxin thioredoxin light-activation system and thylakoids from either mesophyll or bundle-sheath tissues of different C4 plants. While C4-plant thylakoids functionned almost equally well with C3-or C4-plant proteins, the photosyntem-II deficient bundle-sheath thylakoids from the NADP-malic enzyme type, were unable to perform enzyme photoactivation unless supplemented with an electron donor to photosystem I. Bundle-sheath thylakoids isolated from plants showing no photosystem-II deficiency did not require such an addition. The results are discussed with respect to a possible requirement for a physiological reductant of ferredoxin for enzyme light activation in bundle-sheath, tissues. PMID- 24241432 TI - Synthesis of characteristic proteins in nutrient-depleted cell suspension cultures of parsley. AB - Cell suspension cultures of parsley (Petroselinum crispum) exhibited an altered pattern of protein synthesis after transfer from complete growth medium to water or medium containing no macronutrients. Similar changes occurred when cultures were grown in the original medium until the nutrients were depleted. The effect was reversible upon transfer to fresh medium and was not observed during regular subculturing of the cells. While total protein synthesis decreased sharply after nutrient depletion, the synthesis of a few characteristic proteins (starvation related proteins, STPs) increased strongly. The protein labeled at highest rates with [(35)S]methionine in vivo (STP 62) had an apparent molecular weight of about 62000 and a pI of about 6.3. Although its increased rate of synthesis was therefore easily detected by labeling in vivo, translation of mRNA in vitro did not give comparable results. Thus, regulatory control may be exerted mainly at the level of translation. Synthesis of STP ceased rapidly when heat shock (37 degrees C) was applied under conditions of nutrient depletion, whereas heat shock proteins were strongly induced. PMID- 24241433 TI - Molecular analysis of a phytohemagglutinin-defective cultivar of Phaseolus vulgaris L. AB - The seeds of Phaseolus vulgaris cv. Pinto III are known to lack detectable amounts of phytohemagglutinin (PHA) and to accumulate very reduced levels of PHA mRNA compared with normal cultivars. Using PHA complementary-DNA clones and monospecific antibodies we analyzed cv. Pinto III genomic DNA and cotyledonary proteins synthesized both in vitro and in vivo. We detected genomic DNA sequences that hybridize with complementary-DNA clones for the two different classes of PHA polypeptides (PHA-E and PHA-L), at levels comparable to a normal bean cultivar. This indicates that the cv. Pinto III phenotype is not the result of a large deletion of the PHA structural genes. Messenger RNA isolated from cv. Pinto III developing cotyledons synthesizes in vitro very small amounts of a protein which is recognized by antibodies specific for PHA, and gives, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single band with molecular weight similar but not identical to that of PHA-L polypeptides. This protein is also synthesized in vivo at a very reduced level, less than 1% compared with PHA in normal cultivars, and has mitogenic activity comparable to that of the PHA-L subunit, while it shows very weak erythroagglutinating activity. The initial steps in the synthesis and processing of this protein are identical to those already identified for PHA polypeptides. The cv. Pinto III protein could be either a PHA-L polypeptide whose synthesis is not affected by the mutation or a PHA-like lectin present normally at low levels in P. vulgaris. PMID- 24241434 TI - Isolation of plasma-membrane-bound calcium/calmodulin-regulated protein kinase from pea using Western blotting. AB - Membranes isolated from pea buds contain protein-kinase activity which is greatly activated by low concentrations of calcium ions. This paper describes a simple purification of this enzyme with a novel means of detecting enzyme activity by Western blotting. The purified enzyme appears to autophosphorylate primarily on serine residues, is activated by bovine calmodulin and additional evidence from phase partitioning indicate most of this enzyme to be located in the plasma membrane. PMID- 24241436 TI - The relationship between the redox state of Q A and photosynthesis in leaves at various carbon-dioxide, oxygen and light regimes. AB - The response of chlorophyll fluorescence elicited by a low-fluence-rate modulated measuring beam to actinic light and to superimposed 1-s pulses from a high fluence-rate light source was used to measure the redox state of the primary acceptor Q A of photosystem II in leaves which were photosynthesizing under steady-state conditions. The leaves were exposed to various O2 and CO2 concentrations and to different energy fluence rates of actinic light to assess the relationship between rates of photosynthesis and the redox state of Q A. Both at low and high fluence rates, the redox state of Q A was little altered when the CO2 concentration was reduced from saturation to about 600 MUl.l(-1) although photosynthesis was decreased particularly at high fluence rates. Upon further reduction in CO2 content the amount of reduced Q A increased appreciably even at low fluence rates where light limited CO2 reduction. Both in the presence and in the absence of CO2, a more reduced Q A was observed when the O2 concentration was below 2%. Q A was almost fully reduced when leaves were exposed to high fluence rates under nitrogen. Even at low fluence rates, Q A was more reduced in shade leaves of Asarum europaeum and Fagus sylvatica than in leaves of Helianthus annuus and Fagus sylvatica grown under high light. Also, in shade leaves the redox state of Q A changed more during a transition from air containing 350 MUl.l(-1) CO2 to CO2-free air than in sun leaves. The results are discussed with respect to the energy status and the CO2-fixation rate of the leaves. PMID- 24241435 TI - Calcium-binding and its effect on circular dichroism of plant calmodulin. AB - The Ca(2+)-binding properties of calmodulin purified from zucchini (Cucurbita pepo L.) has been determined. A value of 3.3 mol Ca(2+) per mol of zucchini calmodulin was measured at pH 7.5 by equilibrium chromatography. The far-and near UV circular-dichroic spectra of the Ca(2+)-and Mg(2+)-saturated as well as from the metal-free forms of zucchini calmodulin reveal that upon Ca(2+)-binding the alpha-helix content increases. A comparison with the spectra of vertebrate calmodulin indicates that both calmodulin have a similar secondary structure, similar Ca(2+)-induced conformational changes and the same number of Ca(2+) binding sites. PMID- 24241437 TI - Calmodulin dependent NAD-kinase is associated with both the outer and inner mitochondrial membranes in maize roots. AB - Maize root mitochondrial have been subfractionated after osmotic rupture. A calcium-calmodulin-dependent NAD-kinase activity has been shown to be present in both inner and outer membrane fractions. Cytochrome c-reductase activities are also associated with outer and inner membrane fractions but whereas the former is entirely insensitive to 50 MUmol.1(-1) antimycin A the latter is reduced by 60% in its presence. This residual antimycin A-insensitive cytochrome c-reductase activity cosediments with the major portion of NAD-kinase activity and equilibrates in sucrose gradients at densities around 1.146 g.cm(-3). Rate zonal centrifugation with renografin allows an excellent separation of both cytochrome c-reductase and NAD-kinase activities. We have no evidence for allocating NAD kinase activity to endo- or plasma membranes. PMID- 24241438 TI - Sexual agglutination in Chlamydomonas eugametos before and after cell fusion. AB - A new study of sexual agglutination between Chlamydomonas eugametos gametes and between vis-a-vis pairs has been made using techniques that allow one to distinguish between the flagella or cell bodies of individual mating types (mt(+) or mt(-)). It is shown that before mt(+) and mt(-) gametes fuse in pairs, their flagella, which adhere over their whole length, are maintained in a particular conformation around the mt(-) cell body. In clumps of agglutinating gametes the cells are asymmetrically distributed with the mt(+) gametes constituting the outer surface of the clumps with the mt(-) gametes on the inside. The flagella are then all directed towards the middle of the clump. This orientation of the flagella is maintained for approx. 8 min after cell fusion before the vis-a-vis pair becomes motile. At this stage, all the flagellar tips are activated. The original mt(+) flagellar tips then deactivate and swimming is resumed. The original mt(-) flagella remain immotile and activated after cell fusion and eventually shorten by a third, but only 30 min or more after fusion. Motile vis-a vis pairs eventually settle to the substrate when the gamete bodies fuse completely to form a zygote. Settling vis-a-vis pairs are attracted to those that have already settled, to glutaraldehyde-fixed pairs and to flagella isolated from mt(-) gametes. They are not chemotactically attracted, rather they are weakly agglutinated. Living vis-a-vis pairs can be shown to aggregate in rows with the cell bodies lying side by side. It is argued that the flagellar agglutination sites involved in gamete recognition are also involved in vis-a-vis pair aggregation. PMID- 24241439 TI - Transport of basic amino acids in Riccia fluitans: Evidence for a second binding site. AB - The transport of several amino acids with different side-chain characteristics has been investigated in the aquatic liverwort Riccia fluitans. i) The saturation of system I (neutral amino acids) by addition of excess alpha-aminoisobutyric acid to the external medium completely eliminated the electrical effects which are usually set off by neutral amino acids. Under these conditions arginine and lysine significantly depolarized the plasmalemma. ii) L- and D-lysine/arginine were discriminated against in favour of the L-isomers. iii) Increasing the external proton concentration in the interval pH 9 to 4.5 stimulated plasmalemma depolarization, electrical net current, and uptake of [(14)C]-basic amino acids. iv) Uptake of [(14)C]-glutamic acid took place only at acidic pHs. v) [(14)C] histidine uptake had an optimum between pH 6 and 5.5. vi) Overlapping of the transport of basic, neutral, and acidic amino acids was common. It is suggested that besides system I, a second system (II), specific for basic amino acids, exists in the plasmalemma of Riccia fluitans. It is concluded that the amino-acid molecule with an uncharged side chain is the substrate for system I, which also binds and transports the neutral species of acidic amino acids, whereas system II is specific for amino acids with a positively charged side chain. The possibility of system II being a proton cotransport is discussed. PMID- 24241440 TI - Modulation of carrier-mediated uptake of abscisic acid by methyl jasmonate in Phaseolus coccineus L. AB - The effects of methyl jasmonate and jasmonic acid on uptake of abscisic acid (ABA) by suspension-cultured runner-bean cells and subapical runner-bean root segments have been investigated. Increasing concentrations of methyl jasmonate inhibit ABA uptake by the cultured cells with a K i of 22+/-3 MUM. This is not due to cytoplasmic acidification or to effects on metabolism of ABA, and is not additive with inhibition of radioactive ABA uptake by nonradioactive ABA. Uptake of indol-3-yl acetic acid (IAA) is unaffected by methyl jasmonate. The maximum effect of nonradioactive ABA in inhibiting uptake of radioactive ABA, previously shown to reflect saturation of an ABA carrier, is generally greater than the effect of maximally inhibitory concentrations of methyl jasmonate. Similar results were obtained with root segments, but longer incubation times were necessary to observe inhibitory effects of methyl jasmonate. Demethylation of methyl jasmonate to jasmonic acid does not appear to be required since similar concentrations of jasmonic acid had no observable direct effect on ABA uptake other than that attributable to cytoplasmic acidification. Histidine reagents, a proton ionophore and acidic external pH all affect in parallel the inhibition by methyl jasmonate and nonradioactive ABA of uptake of radioactive ABA by the cultured cells. There is no effect of ABA or nonradioactive methyl jasmonate on uptake of radioactive methyl jasmonate by the cultured cells. It is proposed that methyl jasmonate interacts with the ABA carrier. Various models for this interaction are discussed. PMID- 24241441 TI - Variation in cellular ribulose-1,5-bisphosphate-carboxylase content in leaves of Triticum genotypes at three levels of ploidy. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 1.1.39) (RuBPCase) was quantified using polyacrylamide-gel electrophoresis in whole 9-d-old first leaves of 14 genotypes of Triticum, and cellular RuBPCase levels calculated. Diploids, tetraploids and hexaploids were analysed and it was confirmed that the RuBPCase level per cell is closely related to ploidy in wheat. Inter-genotypic variation in RuBPCase levels per cell and per leaf were surveyed. It was found that the interactions between leaf size, cell size and RuBPCase levels result in small variations in RuBPCase levels per unit leaf area between genotypes. PMID- 24241442 TI - Capacity for fermentation in roots and Rhizobium nodules of Pisum sativum L. AB - The aim of this work was to compare the capacities for fermentation and synthesis of malate from phosphoenolpyruvate in roots and Rhizobium nodules of Pisum sativum. The nodules and the cortices and apices of roots had similar activities of glycolytic enzymes and enzymes of ethanolic and lactic fermentation when expressed on a protein basis. The activity of phosphoenolpyruvate carboxylase was similar in nodules and apices, and three to four fold lower in cortices. All three tissues had very high activities of malate dehydrogenase, significant activity of NADP-malic enzyme, and no detectable activity of phosphoenolpyruvate carboxykinase. These results do not support the belief that nodules have a substantially greater capacity to convert phosphoenolpyruvate to malate than roots, or that there are major qualitative differences in the pathways of fermentation of nodules and roots. PMID- 24241443 TI - Regulation of alpha-galactosidase activity and the hydrolysis of galactomannan in the endosperm of the fenugreek (Trigonella foenum-graecum L.) seed. AB - When endosperms were isolated from fenugreek seeds 5 h after sowing and incubated in a small volume of water, the development of alpha-galactosidase activity and the breakdown of the galactomannan storage polysaccharide were both inhibited relative to control endosperms incubated in larger volumes. The inhibition could be relieved by pre-washing the endosperms, and reimposed by the wash-liquors. If the endosperms were isolated 24 h after sowing, no inhibition was observed. Removal of the embryonic axis from germinating fenugreek seeds and from germinated seedlings also inhibited the development of alpha-galactosidase activity and galactomannan breakdown in the endosperms; the inhibition was more pronounced the earlier the axis was removed. Axis excision 5 h after sowing caused a delay in the onset of galactomannan breakdown and of the appearance of alpha-galactosidase activity in the endosperms. It also led to a decrease in the rates of galactomannan breakdown and alpha-galactosidase production. Axis excision 24 h after sowing caused only a slowing of the rates of galactomannan breakdown and alpha-galactosidase increase. The inhibition caused by axis removal at 5 h could be relieved partially by gibberellin (10(-4) M), benzyladenine (10( 5) M), mixtures of these and by the herbicide SAN 9789 [4-chloro-5-(methylamine) 2-(alpha,alpha,alpha-trifluoro-m-tolyl)-3-(2H)-pyridazinone]. These substances had no effect on the inhibition caused by axis-removal at 24 h. Excision of the cotyledons at 5 h-leaving the separated axis and the endosperm-also caused inhibition of galactomannan breakdown and alpha-galactosidase development. The results are consistent with the presence in the fenugreek seed endosperm of diffusible inhibitors of galactomannan mobilisation which are removed or inactivated during normal germination and early seedling development. They are also consistent with a role for the seedling axis in the control of galactomannan breakdown in the endosperm. Initially the axis appears to have a regulatory function (via gibberellins and/or cytokinins?) in determining the onset of alpha galactosidase production in the endosperm. Thereafter its continued presence is necessary to ensure maximal rates of alpha-galactosidase production and galactomannan hydrolysis. The role of the axis may be initially to counteract the endogenous inhibitors in the endosperm and then to act as a sink for the galactomannan breakdown products released in the endosperm and taken up by the cotyledons. PMID- 24241444 TI - Inhibition of stem growth and gibberellin production in Agrostemma githago L. by the growth retardant tetcyclacis. AB - The effects of the new growth retardant tetcyclacis (TCY) on stem growth and endogenous gibberellin (GA) levels were investigated in the long-day rosette plant Agrostemma githago. Application of TCY (10 ml of a 5.10(-5)M solution daily) to the soil suppressed stem elongation in Agrostemma grown under long-day conditions. A total of 10 MUg GA1 (1 MUg applied on alternate days) per plant overcame the growth retardation caused by TCY.Control plants and plants treated with TCY were analyzed for endogenous GAs after exposure to nine long days. The acidic extracts were fractionated by high-performance liquid chromatography. Part of each fraction was tested in the d-5 maize bioassay, while the remainder was analyzed by combined gas chromatography-selected ion monitoring. The bioassay results indicated that the GA content of plants treated with TCY was much lower than that of untreated plants. The data obtained by gas chromatography-selected ion monitoring confirmed that the levels of seven GAs present in Agrostemma were much reduced in TCY-treated plants when compared with the levels in control plants: GA53 (13%), GA44 (0%), GA19 (1%), GA17 (33%), GA20 (15%), GA1 (4%), and epi-GA1 (13%). These results provide evidence that TCY inhibits stem growth in Agrostemma by blocking GA biosynthesis and thus lowering the levels of endogenous GAs. PMID- 24241445 TI - Characteristics of chloroplast thylakoid lipid composition associated with resistance to triazine herbicides. AB - A detailed comparison of the polar-lipid composition of chloroplast thylakoid membranes isolated from triazine-susceptible and triazine-resistant biotypes of Chenopodium album, Senecio vulgaris, Poa annua and Amaranthus retroflexus has been carried out. No major differences in the composition of the bulk lipid matrix were found except for a slightly higher monogalactosyldiacylglycerol to digalactosyldiacylglycerol ratio in resistant compared with susceptible biotypes. There was, however, in the case of resistant plants a higher level of phosphatidylglycerol-containing transhexadecenoic acid in membrane fractions enriched in photosystem two. It is concluded that although the minor differences could contribute to triazine resistance it is more likely that they reflect secondary alterations in membrane organisation associated with changes in relative levels of pigment-protein complexes. PMID- 24241446 TI - Erratum. PMID- 24241447 TI - Third International Stroke Trial 3: an update. AB - PURPOSE OF REVIEW: The third International Stroke Trial (IST-3) was a randomized controlled trial of thrombolysis with intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke within 6 h of onset. It sought to determine whether a wider variety of patients might benefit from treatment than were eligible under the prevailing European Union approval for the drug, especially among those aged over 80 years. RECENT FINDINGS: The entry criteria were broad, and there was no upper age limit for inclusion; over half the 3035 patients were aged over 80 years. For the types of patient recruited in IST-3, despite the early hazards (chiefly of fatal intracerebral hemorrhage), thrombolysis within 6 h did not affect longer-term survival and improved functional outcome. Benefit was greatest among patients treated within 3 h, and benefit did not appear to be diminished among elderly patients or those with severe stroke. SUMMARY: These results should, therefore, encourage clinicians to: consider thrombolytic treatment for a wider variety of patients (particularly those aged over 80 years); treat those with more severe strokes; reinforce their efforts to increase the proportion of ischemic strokes treated within 3 h; and, have greater confidence that mortality is not increased by treatment. VIDEO ABSTRACT: http://links.lww.com/CONR/A23. PMID- 24241448 TI - Effects of inbreeding on economic traits of channel catfish. AB - Inbred channel catfish (Ictalurus punctatus) were produced from two generations of full-sib matings to study the effect of inbreeding on reproduction, growth and survival. A randomly mated control line was propagated from the same base population to be used for the evaluation of the inbred fish. First generation inbred (I1) and control (C1) lines comprised five full-sib families each. Second generation inbred (I2) and control (C2) lines were produced by mating each male catfish from the I1 or C1 line to two females in sequence, one from the I1 and one from the C1 line. The design also produced two reciprocal outcross lines to be compared to their contemporary inbred and control lines. The coefficient of inbreeding for the inbred line increased from 0.25 in generation 1 to 0.375 in generation 2. The inbreeding coefficient was zero for all other lines. The resulting fish were performance tested in two locations, Tifton, Georgia and Auburn, Alabama and no genotype-environment interactions occurred. Results indicated that one generation of inbreeding increased number of days required for eggs to hatch by 21%, but did not significantly influence spawn weight or hatchability score. However, inbred females produced more eggs/kg body weight than control females. Two generations of full-sib mating in Georgia did not depress weight when expressed as a deviation to random controls but was depressed 13-16% when expressed as a deviation to half-sib out-crosses. Second generation inbreds produced in Alabama exhibited a 19% depression for growth rate when compared to either random or half-sib outcross controls. Survival rates at various age intervals was not decreased by inbreeding. The amount of inbreeding depression varied among families and between sexes. PMID- 24241449 TI - Uniformity of plants regenerated from orange (Citrus sinensis Osb.) protoplasts. AB - Using 25 plants (protoclones) regenerated from orange (Citrus sinensis Osb.) protoplasts, several characters, including leaf and flower morphology, leaf oil, isozyme patterns and chromosome number, were examined. No significant variations in each character were recorded among the protoclones. Uniformity observed among protoclones was identical to that of nucellar seedlings. PMID- 24241450 TI - Rearrangements in the mitochondrial genome of somatic hybrid cell lines of Pennisetum americanum (L.) K. Schum. + Panicum maximum Jacq. AB - Mitochondrial DNA from three somatic hybrid cell lines of Pennisetum americanum + Panicum maximum was compared with mitochondrial DNA of the parents. Gel electrophoresis of BamHI-restricted mitochondrial DNA indicated that extensive rearrangements had occurred in each of the three hybrid lines. The hybrid restriction patterns showed a combination of some bands from each parent plus novel fragments not present in either parent. Additional evidence for rearrangements was obtained by hybridization of eight DNA probes, carrying sequences of known coding regions, to Southern blots. Each of the somatic hybrids exhibited a partial combination of the parental mitochondrial genomes. These data suggest recombination or amplification of the mitochondrial genomes in the somatic hybrids. PMID- 24241451 TI - Isozymes and classification of Asian rice varieties. AB - Enzyme variation detected by starch gel electrophoresis was used to investigate the genetic structure of Oryza sativa L. species. Fifteen polymorphic loci coding for 8 enzymes were surveyed among 1688 traditional rices from Asia. Multivariate analysis of the data resulted in identification of six varietal groups, with two major ones, groups I and VI, two minor ones, groups II and V, and two satellite ones, groups III and IV. Group I is found throughout tropical Asia; it encompasses most Aman rices in Bangladesh, the Tjereh rices in Indonesia and the Hsien rices in China. Group VI is found mostly in temperate regions and in high elevation areas in the tropics; it encompasses most upland rices from Southeast Asia, the Bulu rices from Indonesia and the Keng rices from China. Groups II, III, IV and V share common differences from groups I and VI which suggest an alternative evolutionary history. Groups II and V are found in the Indian subcontinent from Iran to Burma. Well-known components of these are Aus rices from Bangladesh for group II and Basmati rices from Pakistan and India for group V. Groups III and IV are restricted to some deepwater rices in Bangladesh and Northeast India. Based on analogy with other classifications, Group I might be considered as the "Indica" type and Group VI as the "Japonica" type. Such terms, however, have a depreciated meaning due to discrepancies among various classifications. PMID- 24241452 TI - Gametoclonal variation detected in the nuclear ribosomal DNA from doubled haploid lines of a spring wheat (Triticum aestivum L., cv. 'Cesar'). AB - The organization of the nuclear ribosomal DNA from a parental line of wheat (Triticum aestivum L., cv. 'Cesar') and its anther-derived first cycle and second cycle doubled haploid lines has been analyzed by DNA-DNA molecular hybridization. Restricted DNA has been probed by three subclones of wheat nuclear ribosomal DNA covering the entire repeat unit. No significant difference was detected in the extent of methylation of ribosomal DNA of the doubled haploid lines with respect to the parental line. On the other hand, a variation has been found in the organization of the nontranscribed spacer region of ribosomal DNA of the first cycle doubled haploid line. This variation remains stable after a second cycle of in vitro androgenesis. However, one out of five second cycle doubled haploid lines so far tested showed an additional hybridization band present in the parental line but lacking in the first cycle doubled haploid line. PMID- 24241453 TI - Viability and behaviour of translocations that suppress female recombination in the Mediterranean fruit fly, Ceratitis capitata (Wied.). AB - The viability of a series of recombination suppressor (RS) strains in Ceratitis capitata, all previously found to contain a reciprocal autosomal translocation, was assessed for egg hatchability and adult emergence in both the homozygous and heterozygous state. Except in T 30C, which contains a Y-autosome translocation in addition to the A-A translocation, egg hatch was significantly reduced in all heterozygous translocation strains, and ranged from 42.4% to 58.5% in seeded eggs compared to a control value of 82.8%. Adult emergence from hatched eggs was affected to a lesser extent, but with a range of 59.5% to 84.2%, compared to the control value of 83.1%, remained significantly reduced in 4 of the 6 translocation strains, as well as in the male line of T 30C. In the homozygous configuration all strains, except T 19 and T 109, showed a significant reduction in egg hatchability, whereas adult emergence was not adversely affected. A significant reduction in the egg hatchability of the translocation heterozygotes compared to that of the homozygotes was observed in 5 of the 7 strains, the observed reduction in T 55/109 being non-significant while that of T 30C was significantly increased. The behaviour of translocations as recombination suppressors and their suitability for inclusion in breeding schemes for the isolation of induced recessive mutations is discussed. PMID- 24241454 TI - Gene assignment by means of somatic cell hybrids: a new method for the analysis of data. AB - A statistical approach to the interpretation of data from gene assignment with somatic cell hybrids is presented. The observed data are analysed under a variety of hypotheses. The fit to the hypotheses is compared by means of the likelihood obtained under a given hypothesis. Two of these hypotheses are related to fundamental questions: is a gene responsible for the enzyme observation and if so, is that gene located on a specific chromosome or could it change its position and be sometimes on chromosome j and, in another hybrid line, on chromosome k? The other hypotheses concern the assignment of the gene to just one of the chromosomes.To improve the traditional data analysis approach we considered additional information: the uncertainties and possible errors of laboratory methods in all our calculations and the length of the donor chromosomes in connection with one specific hypothesis.This method allows us to account for the reliability of the investigation methods and the nature of the hybrid lines involved. Data can be evaluated at different error probabilities within a realistic range in order to compare and discuss results. PMID- 24241455 TI - A 5-methyltryptophan resistant rice mutant, MTR1, selected in tissue culture. AB - Cell lines resistant to tryptophan analogue 5-methyltryptophan (5MT) were selected in seed-derived calli of Oryza sativa L. var. 'Norin 8'. Plants were regenerated (R1 from one selected callus line (MTR1). In three out of the six R1 plants, 5MT resistance was inherited in the R2 and R3 generations as a dominant nuclear mutation. Segregation ratios in the progeny of heterozygous plants were 1?1. Morphological and fertility variation seen in some of the R2 plants were not correlated with 5-methyltryptophan resistance. Resistance in the MTR1 callus was due to the accumulation of high levels of free tryptophan (87-fold) that was associated with an increase in free phenylalanine content (9-fold). The leaves of resistant plants also contained elevated levels of free tryptophan and phenylalanine. PMID- 24241456 TI - Creating new forms of 4x, 6x and 8x primary triticale associating both complete R and D genomes. AB - Strains of Aegilops squarrosa L. and Ae. ventricosa L. were pollinated either by Secale cereale L. or tetraploid triticale. Using in vitro culture of immature F1 embryos, the four corresponding hybrids were obtained. Successful doubling occurred following colchicine treatment, leading to the creation of new amphidiploid structures (C1 plants). These correspond to primary triticale forms involving, at three different levels of ploidy, both R and D full complements. The various combinations were compared for their response at successive steps of the process. Crosses involving Ae. squarrosa present a higher fruit setting than those with Ae. ventricosa, which in contrast yield colchicine treated-plants with better grain fertility. Experimental data on the cytological behaviour and fertility of colchicine-treated as well as amphidiploid plants are presented. The importance of this material in triticale breeding is discussed. PMID- 24241457 TI - Anther culture of Hordeum vulgare L.: a genetic study of microspore callus production and differentiation. AB - The inheritance of the ability of barley anthers to produce microspore-derived callus in vitro was investigated. The genotypes selected were the two spring cultivars 'Dissa' (D) and 'Sabarlis' (S), the two F1 hybrids (DxS, SxD), the two backcross generations [Dx(DxS), Sx(DxS)], and an F2 generation derived from DxS. From a number of individuals of each generation, the first five spikes were harvested sequentially and after pre-treatment the anthers were removed and placed in culture. Cultures were scored for microspore callus production and plantlet differentiation. Although 'Dissa' gave a significantly higher level of callus production than 'Sabarlis', the overall frequencies of green and albino plant production were higher from 'Sabarlis'. There was no significant difference between reciprocal F1 hybrids. Analysis of variance revealed significant differences in response between the spikes sampled from the plants. This was the major source of variation in the experiment. Spike to spike variation also appeared to be a heritable character. PMID- 24241458 TI - Nuclear DNA amplification in cultured cells of Oryza sativa L. AB - Highly repeated nuclear DNA sequences from suspension cultured cells of Oryza sativa L. cv. 'Roncarolo' have been cloned in pBR322. Ten clones with specific digestion patterns have been randomly selected. Nine sequences appear to be organized in a clustered tandem array while one is interpersed in the rice genome. The clones have been used to gather information on: (a) their modulation in cultured cells as compared to whole plant and (b) their distribution in different rice cultivars belonging to the Japonica or Indica subspecies of Oryza sativa L. Hybridization with nuclear DNA isolated either from suspension or from seedlings of the 'Roncarolo' cultivar revealed extensive quantitative variations, with most cloned sequences showing amplification (up to 75-fold) in cultured cells. Hybridization with nuclear DNA isolated from seedlings or suspension cultured cells from different cultivars belonging to the Japonica or to the Indica sub-species of O. sativa have shown that (a) amplification also occurs in a similar pattern in the case of DNA from the other tested suspension cultured cell types but not in the case of DNA from seedlings; (b) in some cases the tested sequences show minor but significant variations in different rice accessions. PMID- 24241459 TI - Electrophoretic analysis of the high-molecular-weight glutenin subunits of Triticum monococcum, T. urartu, and the A genome of bread wheat (T. aestivum). AB - The high molecular weight (HMW) subunit composition of glutenin was analysed by sodium dodecyl sulphate, polyacrylamide gel electrophoresis (SDS-PAGE) in the A genome of 497 diploid wheats and in 851 landraces of bread wheat. The material comprised 209 accessions of wild Triticum monococcum ssp. boeoticum from Greece, Turkey, Lebanon, Armenia, Iraq, and Iran; 132 accessions of the primitive domesticate T. monococcum ssp. monococcum from many different germplasm collections; one accession of free-threshing T. monococcum ssp. sinskajae; 155 accessions of wild T. urartu from Lebanon, Turkey, Armenia, Iraq, and Iran; and landraces of T. aestivum, mainly from the Mediterranean area and countries bordering on the Himalayan Mountains. Four novel HMW glutenin sub-units were discovered in the landraces of bread wheat, and the alleles that control them were designated Glu-Ald through Glu-Alg, respectively. The HMW subunits of T. monococcum ssp. boeoticum have a major, "x" subunit of slow mobility and several, less prominent, "y" subunits of greater mobility, all of which fall within the mobility range of HMW subunits reported for bread wheat. In T. monococcum ssp. monococcum the range of the banding patterns for HMW subunits was similar to that of ssp. boeoticum. However, two accessions, while containing "y" subunits were null for "x" subunits. The single accession of Triticum monococcum ssp. sinskajae had a banding pattern similar to that of most ssp. boeoticum and ssp. monococcum accessions. The HMW subunit banding patterns of T. urartu accessions were distinct from those of T. monococcum. All of them contained one major "x" and most contained one major "y" subunit. In the other accessions a "y" subunit was not expressed. The active genes for "y" subunits, if transferred to bread wheat, may be useful in improving bread-making quality. PMID- 24241460 TI - Somaclonal variation in some agronomic and quality characters in wheat. AB - A total of 256 selected lines derived from tissue culture of three hexaploid wheat cultivars were grown in a replicated hill plot experiment to examine somaclonal variation in agronomic characters. The lines were derived by single plant selection for various characters from a total of 100 regenerants, and were either SC3 or SC4 generation in the test. Significant variation was found in all the characters measured: height, grain number per spike, kernel weight, yield, total dry weight and harvest index. In most cases, variation could be identified which was both less than and greater than the parental controls. However, there was also an apparent effect of the parent cultivar on the total amount and direction of the variation. For two cultivars, lines could be traced back through the culture phase to individual explant embryos. Many of the original embryos contributed significant variation, and most characters showed significant variation arising from more than one embryo. In the following year, 32 lines selected from the hill plot experiment were grown in larger replicated plots and yield, harvest index and a number of grain and baking quality characters were measured. No lines selected for high yield or harvest index maintained significant improvements over their parental controls. However, significant variation was displayed for many of the quality characters examined. Significant increases in kernel weight, hardness and protein content, and a significant reduction in yellow pigmentation represented potentially useful improvements. Only unfavourable variation was seen in flour yield and in mixograph height, time and breakdown. PMID- 24241461 TI - Stability of performance of okra as influenced by planting date. AB - Fifteen selected okra genotypes, consisting of six from a pedigree breeding programme and nine established varieties as checks, were evaluated in five different environments for stability of performance. Performance was measured by pod yield per plant, number of days to flowering, final plant height, number of branches per plant, number of pods per plant and edible pod weight. A regression method and a genotype grouping technique were employed in the evaluation. The results showed significant genotype * environment interaction only with respect to number of days to flowering and number of branches per plant. Additive environmental effect was significant for all characters. Line UI 313 was considered stable with respect to pod yield per plant and edible pod weight. One line resulting from the pedigree breeding programme was also considered stable by the genotype-grouping technique. PMID- 24241462 TI - Estimating relative fitness in asexually reproducing plant pathogen populations. AB - A mathematical model is presented and analysed to find the conditions under which changes in gene frequencies can be used in asexually reproducing populations for estimating fitness of single genes, for example, for estimating the fitnesses of unnecessary virulence genes relative to their corresponding avirulence genes. It is concluded that the underlying distribution of relative fitness of clones (genotypes) has to be unimodal and that many populations consisting of a mixture of distinguishable clones then provide the best experimental data for estimating relative fitness of single genes. An improved statistical test procedure, i.e. generalized logistic regression, is suggested for analysing changes in gene frequencies in population experiments with a mixture of distinguishable clones. A population study of Erysiphe graminis f.sp. hordei (Klug-Andersen 1980) provides data to illustrate the procedure in the case where the population consists of a large number of genotypes. A bimodal distribution of "genotypes" possessing the virulence gene is indicated here. PMID- 24241463 TI - Improved rate of callus induction from rice anther culture following microscopic staging of microspores in iron alum-haematoxylin. AB - High frequencies of callusing were obtained in indica rice from the microspores which were staged in acetic acid iron alum-haematoxylin stain prior to culture on G5 medium. Two local varieties, 'Khonorullo' and 'Namyi', and two advance pre release cultures, 'PK 1-1-3' and 'PK 12-22', were used in this investigation. All the cultures exhibited a wide adaptation to varying medium; however, the frequency of callusing was highest (45.5%) in 'PK 1-1-3' followed by 'PK 12-22' (32.4%) and 'Khonorullo' (31.6%). Cold shock (10 degrees C) for 11 days enhanced the frequency of callusing by 200% in 'Khonorullo'. PMID- 24241464 TI - Callus induction from protoplasts of V. unguiculata, V. sublobata and V. mungo. AB - Protoplasts were isolated from hypocotyl of V. mungo (L.) Hepper or hypocotyl derived callus of V. sublobata (Phaseolus sublobata Roxb.) and V. unguiculata (L.) Walp (syn. V. sinensis (L.) Saviex Hassk) using an enzyme solution comprising Cellulase 2.5%, Macerozyme, Hemicellulase and Driselase each at a 0.5% level in 0.5 M sorbitol. Isolated protoplasts were cultured in Murashige and Skoog's (1962) basal liquid medium supplemented with BA, NAA, 2,4-D (1 mg/l each) and sucrose (14%). After four weeks, protoplast colonies were transferred to the same medium with a reduced level of sucrose (7%). Colonies proliferated into actively growing calli. Further attempts to regenerate plants from such calli were not successful. However, protoclones of V. unguiculata differentiated roots on auxin/cytokinin supplemented media. Alternative methods for shoot differentiation from protoplastderived cultures were tried by the use of Agrobacterium tumefaciens "shooter" strains pGV 2215 or pGV 2298 or wild type strain B6S3. PMID- 24241465 TI - Heritable somaclonal variation in wild barley (Hordeum spontaneum). AB - Progenies of H. spontaneum plants regenerated from immature embryo derived calli were analysed for somaclonal variation on the following traits: (1) organization of the intergenic spacer of the rRNA genes; (2) B and C hordein pattern on SDS PAGE; (3) genomic organization of the B and C hordein coding sequences; (4) mitochondrial DNA organization assayed by hybridization of Southern blots of total DNA with mitochondrial coding genes; (5) cytology. One out of twelve progeny plants was characterized as variant for two traits: (a) a loss of 1.8 and 2.5 kb Taq I intergenic rDNA spacer fragments and (b) a variant pattern of hordeins on 1-D SDS-PAGE. No numerical or structural chromosome variation was detected among the control plants therefore it is assumed that the variation was caused by the in vitro culture and transmitted, through sexual reproduction, to the analysed progeny. PMID- 24241466 TI - Genetics of grain amaranths : 4. Variation and early generation response to selection in Amaranthus cruentus L. AB - Two landrace populations of Amaranthus cruentus L. were crossed to generate F2 populations for quantitative genetic analyses of variation. Evidence for significant inbreeding depression in comparisons of F1 and F2generation means suggested some role of nonadditive gene action for days to first anthesis, leaf length, leaf width, petiole length, plant height, panicle length, and panicle weight. A pooled F2 population was subjected to bidirectional mass selection for time of first anthesis (two cycles) and leaf length (one cycle). Responses to selection were asymmetrical and the second cycle response for anthesis time was smaller than for the first cycle. Overall, selection gains were significant and gave estimates of heritability in the range of 0.35 to 0.66 for anthesis time and 0.08 to 0.19 for leaf length. This suggested a large additive term in the total genetic variance especially for anthesis time where early and late flowering selection lines diverged by 20.5 days.Correlations between the selected traits (anthesis time, leaf length) and single plant yield or yield components were also studied to evaluate correlated responses to selection. Selection for optimal flowering time in amaranth cultivation areas is very likely to result in rapid yield improvement. PMID- 24241467 TI - Plant regeneration by pollen embryogenesis from cultured whole spikes of barley (Hordeum vulgare). AB - Pollen embryogenesis and subsequent plant regeneration have been established from cultured whole barley spikes in agitated N6 liquid medium (Chu 1978) containing high levels of 2,4-D, Ficoll and potato extract. Microspore division within the anthers and subsequent embryogenic development were obtained in medium containing high amounts of reduced nitrogen with Zeatin, NAA and BAP (all at 0.5 mg/l levels, pH 6.2). Once embryoids were formed in the liquid medium, they produced secondary embryoids from the scutellum and subsequently plants on MS (Murashige and Skoog 1962) agar medium containing BAP and NAA. The ratio of green plants to albino was 1?8.7. PMID- 24241468 TI - A model for the evolution of the Vicia faba chloroplast genome. AB - The Vicia faba chloroplast genome lacks inverted repeat sequences and contains only one set of ribosomal RNA genes. The genetic organization has been altered by inversions, relative to the typical arrangement of most higher plant chloroplast genomes. The Vicia faba plastid genome thus represents one of the more interesting results of chloroplast genomic evolution. The present study employs small DNA probes and Southern blot hybridizations to investigate the steps involved in the evolution of the Vicia faba chloroplast genome. The data from heterologous hybridizations between chloroplast DNA of Brassica napus (a conserved genome) and of Vicia faba led to three observations: 1) The inverted repeat segment closest to the psbA gene was deleted prior to the rearrangements. 2) A quarter of the ancestral small single copy region was lost during the deletion. 3) The genetic organization observed in Vicia faba resulted from three inversions after the deletion event. Our findings, combined with previous observations, helped devise a stepwise model for the evolution of the Vicia faba chloroplast genome. The area of the small single copy region absent from the Vicia faba chloroplast chromosome lacks in vivo transcription activity in Brassica napus. PMID- 24241469 TI - Chromosome variation in dividing protoplasts and cell suspensions of wheat. AB - The cytology of bread wheat (Triticum aestivum) suspension lines, recycled lines (selected for high division frequency) and their dividing protoplasts, have been examined. Extensive numerical and structural chromosome variation was present in all the lines. The most frequently observed chromosome numbers were around 2n=32, indicating that considerable chromosome loss from the normal wheat complement (2n=6x=42) had occurred during selection of the lines. Chromosome aberrations also indicated loss of chromosome arms and chromosome segments. The implications of this variation for studies on transformation and for the potential regeneration of whole plants from protoplasts of bread wheat are discussed. PMID- 24241470 TI - A cytogenetic characterization comparing a rat 6TG-resistant strain and 6TG sensitive clones. AB - A 8.3 MU/ml 6-thioguanine (6TG)-resistant strain was isolated from a rat tetraploid cell line by step-by-step selection in 6TG-medium. In the 6TG resistant cell population 51% of the cells were tetraploid and 35% of the cells were hypertetraploid, i.e., one chromosome more than a tetraploid. The 6TG resistant strain grew very well in RPMI 1640 medium with intervals of three days between subcultures. The 6TG-resistant cells all have a homogeneously staining region (HSRs) in one of the X chromosomes which do not stain after chromosome C banding. They also possess a higher NORs activity and much lower frequency of sister chromatid exchanges (SCE). When the 6TG-resistant RCT cells were subcultured in 6TG-free medium for three days, their SCE frequency did not change. 5'-bromodeoxyuridine (BrdU) significantly suppressed the NORs activity for both 6TG-resistant cells and 6TG-sensitive cells (P<0.001). PMID- 24241471 TI - Inheritance and linkage relationships of glutamate oxaloacetate transaminase isoenzymes in apple : 1. The gene GOT-1, a marker for the S incompatibility locus. AB - Four zones of enzymatic activity for glutamate oxaloacetate transaminase (GOT) were found in apple tissue. A dimeric gene, GOT-1, determining the fastest migrating zone, was identified. Six alleles were found, including a near null allelle which produced detectable heterodimeric bands but not homodimeric bands. A marked deficit or absence of certain geno-types in all backcrosses and in some crosses between unrelated varieties was attributed to the close linkage (r=0.02+/ 0.005) of GOT-1 with the incompatibility S locus. GOT-1 was also closely linked with the isocitrate dehydrogenase locus IDH-1 (0.03+/-0.01). Proposed incompatibility genotypes for four cultivars, and the linked GOT-1 alleles are 'Cox': S 1 b/S 2 d, 'Idared': S 3 a/S 4 c, 'Fiesta': S 3 a/S 2 d and 'Kent': S 3 a/S 1 b. PMID- 24241472 TI - Genetic analysis of Verticillium wilt tolerance in cotton using pedigree data from three crosses. AB - Three crosses and descendant generations were used in a field study of the inheritance of tolerance to Verticillium wilt, caused by Verticillium dahliae Kleb., in upland cotton (Gossypium hirsutum L.). The tolerant cultivar 'Acala SJC 1' was crossed to more susceptible parents, breeding line S5971 and cultivars 'Acala 4-42' and 'Deltapine 70'. Seven generations were evaluated for each cross: the two parents (P1 and P2), F1; F2, F3, and reciprocal backcrosses (B1 and B2). The genetic control of tolerance in these crosses appears to involve more than one gene, based on an unsatisfactory fit to expected phenotypic distributions for the generations under a single-locus model. An analysis of generation means indicated that pooled additive and pooled dominance effects over loci were adequate to explain the variation among generations for crosses of SJC-1 X S5971 and SJC-1 X DPL70. Tolerance in these crosses appeared to be controlled by recessive factors. For the SJC-1 X 4-42 cross, an adequate fit to a digenic epistatic model was not possible, and none of the genetic parameters except the F2 mean were significant. Heritabilities for tolerance to Verticillium wilt, determined from regressions of F3 progeny on F2 parents for the crosses of SJC-1 X S5971 and SJC-1 X DPL70, ranged from 0.12 to 0.28. Therefore, individual plant selection for improved tolerance is expected to be inefficient. PMID- 24241473 TI - Isolation of mitochondrial DNA from cytoplasmic male sterile and maintainer lines of pearl millet, Pennisetum americanum (L.) Leeke. AB - Mitochondrial DNA has been isolated from paired lines of pearl millet maintainer and cytoplasmic male sterile plants. Evaluation of the DNA by agarose gel electrophoresis shows that good quality DNA of high molecular weight can be obtained from mitochondria of both maintainer and male sterile pearl millet. PMID- 24241475 TI - Erratum. PMID- 24241474 TI - Inheritance of fruit-coat colours in Trichosanthes anguina Linn. AB - In Trichosanthes anguina Linn. (Cucurbitaceae), reciprocal crosses among three naturally occurring fruit-coat colour varieties (deep green, green and white) and two yellow fruit-coat colour mutants isolated in the M1 generation showed that a multiple allelic series control the fruit-coat colours. In the F2 generation the fruit-coat colours segregated in a monohybrid ratio with deep green dominant over green, yellow and white, green dominant over yellow and white, and yellow dominant over white. Two yellow fruit-coat colour mutants used in this study were isolated from X-ray- and EMS-treated populations of a white fruit-coat colour variety. PMID- 24241476 TI - Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study. AB - The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders. PMID- 24241477 TI - Effect of pubertal nano-TiO2 exposure on testosterone synthesis and spermatogenesis in mice. AB - Titanium dioxide nanoparticles (nano-TiO2) are frequently used in cosmetics, paints, sunscreens and the like. Recent studies have demonstrated that nano-TiO2 might be deleterious for the male reproductive function. However, the effects of pubertal nano-TiO2 exposure on testosterone (T) synthesis and spermatogenesis remained to be elucidated. Here, we investigated the effect of pubertal nano-TiO2 exposure on the synthesis of T and spermatogenesis. Nano-TiO2 was orally administered daily to Kunming male mice from 28th postnatal day (PND 28) to PND 70. The percentage of spermatozoa abnormality in epididymides was markedly increased in mice exposed to nano-TiO2; decreased layers of spermatogenic cells and vacuoles in seminiferous tubules were also observed in the nano-TiO2 treated group. In addition, pubertal nano-TiO2 exposure significantly decreased the serum T levels in male mice. Moreover, mice exposures to nano-TiO2 significantly reduced the expression of 17beta-hydroxysteroid dehydrogenase and P450 17alpha hydroxysteroid dehydrogenase in the testis of mice, while the expression of cytochrome P450-19, a key enzyme for the translation of T to estradiol (E2), was increased. Taken together, these results indicated that nano-TiO2 could influence the levels of serum T through changes in both the synthesis and translation of T. Furthermore, the decreased serum T synthesis might contribute to the reduced spermatogenesis in mice exposed to nano-TiO2. PMID- 24241478 TI - Port-site recurrence after complete resection of stage I thymoma by video assisted thoracoscopic surgery: report of a case. AB - A 62-year-old female with myasthenia gravis and a mediastinal tumor underwent extended thymothymectomy by video-assisted thoracoscopic surgery (VATS). The tumor was diagnosed as a stage I type B2 thymoma. Eight years after the initial surgery, an abnormal shadow was detected on the annual follow-up chest radiograph, and computed tomography showed a homogeneous 35 * 15 mm hemispherical mass under a port-site scar in the right anterior chest wall. The mass was between the second and third ribs and was found to be adherent to the lung during surgery, and was excised via lung and chest wall resection. The pathological examination confirmed that it was a type B2 thymoma invading the third rib, and the tumor was considered to be a port-site recurrence. Care should be taken during VATS to avoid contact between the tumor surface and the port tracts to prevent tumor cell implantation. PMID- 24241479 TI - Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case. AB - We monitored serum p53 antibody (s-p53-Ab) titers in a 76-year-old man with esophageal adenocarcinoma, clinical stage III (T2N2M0), for over 4 years, including during the perioperative period and throughout follow-up after surgery. Screening tests for CA19-9 (205 IU/ml) and s-p53-Abs (381 U/ml) were positive before treatment. After neoadjuvant chemotherapy with 5-FU and cisplatin, CA19-9 decreased to the normal range, but the s-p53-Ab titer remained positive (224 U/ml). Pathological findings of surgically resected specimens showed stage T1b disease and no lymph node metastases. After surgery, s-p53-Ab titers consistently decreased, with no disease recurrence. Although the s-p53-Ab titer remained positive even after 4 years, it decreased to 8.66, 3.59, 2.38, and 1.92 U/ml, 1, 2, 3, and 4 years after surgery, respectively. Thus, monitoring perioperative changes in s-p53-Ab titers proved useful for detecting the presence of residual cancer cells in a patient with superficial esophageal adenocarcinoma. PMID- 24241480 TI - Hierarchical branched Cu2O nanowires with enhanced photocatalytic activity and stability for H2 production. AB - Hierarchical branched Cu2O nanowires were synthesized under mild conditions and exhibit remarkable performance for photocatalytic H2 generation from water. The obtained results open appealing perspectives for converting solar energy into storable chemical energy. PMID- 24241481 TI - Repeated anticitrullinated protein antibody and rheumatoid factor assessment is not necessary in early arthritis: results from the ESPOIR cohort. AB - OBJECTIVE: Presence and levels of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) contribute to the classification and prognosis of rheumatoid arthritis (RA). The objective was to determine the usefulness of repeating anti-CCP/RF measurements during the first 2 years of followup in patients with early arthritis. METHODS: In patients with early undifferentiated arthritis, serial anti-CCP and RF were measured using automated second-generation assays every 6 months for 2 years. Frequencies of seroconversions (from negative to positive or the reverse) and changes in antibody levels during followup were determined. RESULTS: In all, 775 patients, mean (SD) age 48.2 (12.5) years, mean symptom duration 3.4 (1.7) months, 76.6% female, were analyzed; 614 (79.2%) satisfied the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA at baseline. At baseline, respectively for anti-CCP and RF, 318 (41.0%) and 181 (23.4%) patients were positive, of whom 298 (93.7% of the positive) and 111 (61.3% of the positive) were highly positive (above 3 * upper limit of the norm). There were only 12 anti-CCP seroconversions toward the positive (i.e., 2.6% of the anti-CCP-negative), 21 seroconversions toward the negative (6.6% of the anti CCP-positive), and 8 (1.0%) changes to a higher anti-CCP level category during the 2-year followup; respectively for RF, 27 (4.6%), 95 (52.5%), and 13 (1.7%). CONCLUSION: In this cohort of patients with early arthritis, including in the subset of patients who did not fulfill the RA criteria, antibody status showed little increase over a 2-year period. Repeated measurements of anti-CCP/RF very infrequently offer significant additional information. PMID- 24241482 TI - Responsiveness in rheumatoid arthritis. a report from the OMERACT 11 ultrasound workshop. AB - OBJECTIVE: To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop. METHODS: The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA. RESULTS: The US GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing. CONCLUSION: At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis. PMID- 24241483 TI - Preliminary validation of 2 magnetic resonance image scoring systems for osteoarthritis of the hip according to the OMERACT filter. AB - OBJECTIVE: Development of a validated magnetic resonance image (MRI) scoring system is essential in hip OA because radiographs are insensitive to change. We assessed the feasibility and reliability of 2 previously developed scoring methods: (1) the Hip Inflammation MRI Scoring System (HIMRISS) and (2) the Hip Osteoarthritis MRI Scoring System (HOAMS). METHODS: Six readers (3 radiologists, 3 rheumatologists) participated in 2 reading exercises. In Reading Exercise 1, MRI of the hip of 20 subjects were read at a single time point followed by further standardization of methodology. In Reading Exercise 2, MRI of the hip of 18 subjects from a randomized controlled trial, assessed at 2 timepoints, and 27 subjects from a cross-sectional study were read for HIMRISS and HOAMS bone marrow lesions (BML) and synovitis. Reliability was assessed using intraclass correlation coefficient (ICC) and kappa statistics. RESULTS: Both methods were considered feasible. For Reading 1, HIMRISS ICC were 0.52, 0.61, 0.70, and 0.58 for femoral BML, acetabular BML, effusion, and total scores, respectively; and for HOAMS, summed BML and synovitis ICC were 0.52 and 0.46, respectively. For Reading 2, HIMRISS and HOAMS ICC for BML and synovitis-effusion improved substantially. Interobserver reliability for change scores was 0.81 and 0.71 for HIMRISS femoral and HOAMS summed BML, respectively. Responsiveness and discrimination was moderate to high for synovitis-effusion. Significant associations were noted between BML or synovitis scores and Western Ontario and McMaster Universities Osteoarthritis Index pain scores for baseline values (p <= 0.001). CONCLUSION: The BML and synovitis-effusion components of both HIMRISS and HOAMS scoring systems are feasible and reliable, and should be validated further. PMID- 24241484 TI - Experiences with rituximab for the treatment of autoimmune diseases with ocular involvement. AB - OBJECTIVE: To report the efficacy of rituximab (RTX) in the treatment of ocular or orbital inflammation accompanying autoimmune diseases refractory to previous standard immunosuppressive therapy. METHODS: We reviewed medical records of 9 consecutive patients with noninfectious ocular or orbital inflammation treated with RTX. RESULTS: Over a mean followup of 42 months, 7 patients were in clinical remission, 1 had partial response to treatment, and 1 did not respond. Best corrected visual acuity improved >= 1 line in 4 patients, was stable in another 4 patients, and worsened in 1. Concomitant immunosuppressive therapy was tapered in 6 cases. Systemic corticosteroids were tapered or kept below 7.5 mg a day in 5 patients 1 year after the first RTX cycle. CONCLUSION: RTX therapy, in patients who are refractory to standard immunosuppressive therapy, was effective and showed a beneficial response to treatment including induction of clinical remission of inflammation in most patients. PMID- 24241485 TI - Item response theory, computerized adaptive testing, and PROMIS: assessment of physical function. AB - OBJECTIVE: Patient-reported outcome (PRO) questionnaires record health information directly from research participants because observers may not accurately represent the patient perspective. Patient-reported Outcomes Measurement Information System (PROMIS) is a US National Institutes of Health cooperative group charged with bringing PRO to a new level of precision and standardization across diseases by item development and use of item response theory (IRT). METHODS: With IRT methods, improved items are calibrated on an underlying concept to form an item bank for a "domain" such as physical function (PF). The most informative items can be combined to construct efficient "instruments" such as 10-item or 20-item PF static forms. Each item is calibrated on the basis of the probability that a given person will respond at a given level, and the ability of the item to discriminate people from one another. Tailored forms may cover any desired level of the domain being measured. Computerized adaptive testing (CAT) selects the best items to sharpen the estimate of a person's functional ability, based on prior responses to earlier questions. PROMIS item banks have been improved with experience from several thousand items, and are calibrated on over 21,000 respondents. RESULTS: In areas tested to date, PROMIS PF instruments are superior or equal to Health Assessment Questionnaire and Medical Outcome Study Short Form-36 Survey legacy instruments in clarity, translatability, patient importance, reliability, and sensitivity to change. CONCLUSION: Precise measures, such as PROMIS, efficiently incorporate patient self-report of health into research, potentially reducing research cost by lowering sample size requirements. The advent of routine IRT applications has the potential to transform PRO measurement. PMID- 24241486 TI - Methodologies for semiquantitative evaluation of hip osteoarthritis by magnetic resonance imaging: approaches based on the whole organ and focused on active lesions. AB - OBJECTIVE: As a wider variety of therapeutic options for osteoarthritis (OA) becomes available, there is an increasing need to objectively evaluate disease severity on magnetic resonance imaging (MRI). This is more technically challenging at the hip than at the knee, and as a result, few systematic scoring systems exist. The OMERACT (Outcome Measures in Rheumatology) filter of truth, discrimination, and feasibility can be used to validate image-based scoring systems. Our objective was (1) to review the imaging features relevant to the assessment of severity and progression of hip OA; and (2) to review currently used methods to grade these features in existing hip OA scoring systems. METHODS: A systematic literature review was conducted. MEDLINE keyword search was performed for features of arthropathy (such as hip + bone marrow edema or lesion, synovitis, cyst, effusion, cartilage, etc.) and scoring system (hip + OA + MRI + score or grade), with a secondary manual search for additional references in the retrieved publications. RESULTS: Findings relevant to the severity of hip OA include imaging markers associated with inflammation (bone marrow lesion, synovitis, effusion), structural damage (cartilage loss, osteophytes, subchondral cysts, labral tears), and predisposing geometric factors (hip dysplasia, femoral acetabular impingement). Two approaches to the semiquantitative assessment of hip OA are represented by Hip OA MRI Scoring System (HOAMS), a comprehensive whole organ assessment of nearly all findings, and the Hip Inflammation MRI Scoring System (HIMRISS), which selectively scores only active lesions (bone marrow lesion, synovitis/effusion). Validation is presently confined to limited assessment of reliability. CONCLUSION: Two methods for semiquantitative assessment of hip OA on MRI have been described and validation according to the OMERACT Filter is limited to evaluation of reliability. PMID- 24241487 TI - Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10-year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open-label extension. AB - OBJECTIVE: To evaluate the longterm safety of adalimumab administered with or without methotrexate (MTX) and compare the efficacy of combination therapy initialization to adalimumab or MTX monotherapy initialization during the open label extension (OLE) of the PREMIER trial (ClinicalTrials.gov Identifier:NCT00195663). METHODS: Patients with early rheumatoid arthritis (RA) were randomized to receive blinded adalimumab + MTX, adalimumab alone, or MTX alone for 2 years. Following the double-blinded period, patients enrolling in the OLE were given adalimumab for up to 8 additional years, beginning as monotherapy; investigators could add MTX at their discretion. Results for clinical, functional, and radiographic progression were collected for up to 10 years of treatment. RESULTS: During the PREMIER OLE, 250/497 patients (50.3%) completed the trial without new safety signals arising. Similar proportions of patients discontinued the trial early, although lack of efficacy was reported less often for patients initially randomized to the adalimumab + MTX arm (9.3%; 21.2%, and 23.7% for adalimumab and MTX monotherapies, respectively). Clinical and functional disease control was maintained throughout the trial. Patients initially randomized to adalimumab + MTX displayed better outcomes, particularly in prevention of radiographic progression (modified total Sharp score change = 4.0, 8.8, 11.0 at Year 10 for the initial adalimumab + MTX, adalimumab, and MTX arms, respectively). CONCLUSION: Intensive therapy with adalimumab + MTX combination in patients with early RA has longterm benefits compared to patients initiating with 2-year adalimumab or MTX monotherapy that persists up to 10 years following adalimumab OLE. No new safety findings were observed following longterm adalimumab treatment. PMID- 24241488 TI - Patient- versus physician-reporting of symptoms and health status in chronic myeloid leukemia. AB - The main objective of this study was to compare the reporting of health status and symptom severity, for a set of core symptoms related to imatinib therapy, between chronic myeloid leukemia patients and their treating physicians. Patients were asked to complete a questionnaire including questions on symptom severity and health status. The symptoms assessed were: abdominal discomfort, diarrhea, edema, fatigue, headache, muscle cramps, musculoskeletal pain, nausea and skin problems. The physicians were asked to complete a questionnaire for each of their patients entering the study. Four hundred twenty-two patients were included in the study. All respective paired physicians (n=29) completed the questionnaire, and thus the analyses are based on 422 patient-physician dyads. Agreement on symptom ratings ranged from 34% (for muscle cramps) to 66% (for nausea). For all symptoms, patients reported higher severity more often than their physicians. The three symptoms whose severity was most frequently underestimated by physicians were fatigue (51%), muscle cramps (49%) and musculoskeletal pain (42%). Health status was overestimated by physicians in 67% of the cases. Physicians and their patients with chronic myeloid leukemia often disagree in their ratings of the patients' symptom severity. Most typically, physicians tend to underestimate symptom severity and overestimate the overall health status of their patients. Current findings support the use of patient-reported outcome measures as a possible means to enhance the management of patients with chronic myeloid leukemia. PMID- 24241489 TI - Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors. AB - Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age >=60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged >=60 years. In multivariate analysis, the donor type/age group and the graft CD34(+) and CD3(+) cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor >=60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34(+) cell dose more than 4.5*10(6)/kg (HR: 0.56; P=0.002) and CD3(+) cell dose more than 3*10(8)/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82). PMID- 24241490 TI - Copy number genome alterations are associated with treatment response and outcome in relapsed childhood ETV6/RUNX1-positive acute lymphoblastic leukemia. AB - The clinical heterogeneity among first relapses of childhood ETV6/RUNX1-positive acute lymphoblastic leukemia indicates that further genetic alterations in leukemic cells might affect the course of salvage therapy and be of prognostic relevance. To assess the incidence and prognostic relevance of additional copy number alterations at relapse of the disease, we performed whole genome array comparative genomic hybridization of leukemic cell DNA from 51 patients with first ETV6/RUNX1-positive relapse enrolled in and treated according to the relapse trials ALL-REZ of the Berlin-Frankfurt-Munster Study Group. Within this cohort of patients with relapsed ETV6/RUNX1-positive acute lymphoblastic leukemia, the largest analyzed for genome wide DNA copy number alterations to date, alterations were present in every ETV6/RUNX1-positive relapse and a high proportion of them occurred in recurrent overlapping chromosomal regions. Recurrent losses affected chromosomal regions 12p13, 6q21, 15q15.1, 9p21, 3p21, 5q and 3p14.2, whereas gains occurred in regions 21q22 and 12p. Loss of 12p13 including CDKN1B was associated with a shorter remission duration (P=0.009) and a lower probability of event-free survival (P=0.001). Distribution of X-chromosomal copy number alterations was gender-specific: whole X-chromosome loss occurred exclusively in females, gain of Xq only in males. Loss of the glucocorticoid receptor gene NR3C1 (5q31.3) was associated with a poor response to induction treatment (P=0.003), possibly accounting for the adverse prognosis of some of the ETV6/RUNX1-positive relapses. PMID- 24241491 TI - Quality of life associated with sirolimus for prevention of graft-versus-host disease: results from a randomized trial. AB - Several studies have examined sirolimus-based immune suppression for the prevention of graft-versus-host disease after allogeneic hematopoietic cell transplantation, but little is known regarding its effects on quality of life. The current study reports on changes in quality of life to Day 360 in a randomized phase II trial of sirolimus and tacrolimus versus methotrexate and tacrolimus. Quality of life was assessed prior to transplant and on Days 30, 90, 180, 270, and 360 with the Functional Assessment of Cancer Therapy - Bone Marrow Transplant Trial Outcome Index. Random effects models examined the effects of study arm on change in Trial Outcome Index scores from Day 30 to 360, controlling for base-line Trial Outcome Index. The sirolimus/tacrolimus arm (n=37) showed less improvement in Trial Outcome Index scores over time compared to the methotrexate/tacrolimus arm (n=34) (P=0.02). Patients receiving sirolimus and tacrolimus were more likely to endorse nausea and a lack of energy over time (PS<=0.01). These data suggest that sirolimus-based immune suppression is associated with less improvement in quality of life in the first year post transplant compared to methotrexate/tacrolimus. Quality of life differences may be due to increased fatigue and nausea in patients treated with sirolimus. These findings should be considered in the clinical management of patients treated with sirolimus. (Clinicaltrials.gov identifier:00803010). PMID- 24241492 TI - Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura. AB - Anti-ADAMTS13 autoantibodies are the main cause of acquired thrombotic thrombocytopenic purpura. Binding of these antibodies to ADAMTS13 eventually results in the formation of antigen-antibody immune complexes. Circulating ADAMTS13-specific immune complexes have been described in patients with acquired thrombotic thrombocytopenic purpura, although the prevalence and persistence of these immune complexes over time have hitherto remained elusive. Here, we analyzed a large cohort of patients with acquired thrombotic thrombocytopenic purpura for the presence of free and complexed anti-ADAMTS13 antibodies. In the acute phase (n=68), 100% of patients had free IgG antibodies and 97% had ADAMTS13 specific immune complexes. In remission (n=28), 75% of patients had free antibodies (mainly IgG) and 93% had ADAMTS13-specific immune complexes. Free antibodies were mainly of subclasses IgG1 and IgG4, whereas IgG4 was by far the most prevalent in ADAMTS13-specific immune complexes. Comparison of ADAMTS13 inhibitor and anti-ADAMTS13 IgG (total and subclasses) antibody titers in acute phase and in remission samples showed a statistically significant decrease in all parameters in remission. Although non-significant, a trend towards reduced or undetectable titers in remission was also observed for ADAMTS13-specific immune complexes of subclasses IgG1, IgG2 and IgG3. No such trend was discernible for IgG4; IgG4 immune complexes persisted over years, even in patients who had been treated with rituximab and who showed no features suggesting relapse. PMID- 24241493 TI - Intentional donor lymphocyte-induced limited acute graft-versus-host disease is essential for long-term survival of relapsed acute myeloid leukemia after allogeneic stem cell transplantation. AB - The prognosis of patients with relapsed acute myeloid leukemia after allogeneic transplantation is poor. We hypothesized that initial disease control by effective cytoreduction, followed by rapid induction of a profound allo-immune response by donor-lymphocyte infusion during the neutropenic phase, is essential for long-term survival. Additional interferon-alpha was administered when no acute graft-versus-host-disease occurred within 3 weeks after donor-lymphocyte infusion. Overall, 44 patients with relapsed acute myeloid leukemia were assessed; 26 had relapsed after myeloablative conditioning and 18 after reduced intensity conditioning. Of these 44 patients, seven were not eligible for cytoreductive treatment because of poor performance status (n=3) or severe graft versus-host-disease (n=4) at the time of relapse. Patients with smoldering relapses (n=5) received donor-lymphocyte infusion only. Thirty-two patients received cytoreductive treatment, followed by donor-lymphocyte infusion in 22 patients. Reasons for not receiving donor-lymphocyte infusion were chemotherapy related death (n=1) and chemotherapy-refractory disease (n=9). The 2-year overall survival rate after donor-lymphocyte infusion was 36% (95% confidence-interval: 16-57%). The impact of acute graft-versus-host-disease on survival was calculated with a Cox-regression model including onset of acute graft-versus-host-disease as a time-dependent variable. Development of grade 1-3, but not grade 4, acute graft versus-host-disease was associated with superior survival as compared to absence of graft-versus-host-disease (hazard ratio 0.22, P=0.03). In conclusion, efficient cytoreduction followed by donor-lymphocyte infusion and subsequent interferon-alpha leading to limited acute graft-versus-host-disease represents a potentially curative option for patients with relapsed acute myeloid leukemia after allogeneic transplantation. PMID- 24241494 TI - Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. AB - Multiple myeloma still remains incurable in the majority of cases prompting a further search for new and better prognostic markers. Emerging evidence has suggested that circulating microRNAs can serve as minimally invasive biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. In this study, a global analysis of serum microRNAs by TaqMan Low Density Arrays was performed, followed by quantitative real-time PCR. The analyses revealed five deregulated microRNAs: miR-744, miR-130a, miR-34a, let-7d and let-7e in monoclonal gammopathy of undetermined significance, newly diagnosed and relapsed multiple myeloma when compared to healthy donors. Multivariate logistical regression analysis showed that a combination of miR-34a and let-7e can distinguish multiple myeloma from healthy donors with a sensitivity of 80.6% and a specificity of 86.7%, and monoclonal gammopathy of undetermined significance from healthy donors with a sensitivity of 91.1% and a specificity of 96.7%. Furthermore, lower levels of miR-744 and let-7e were associated with shorter overall survival and remission of myeloma patients. One-year mortality rates for miR-744 and let-7e were 41.9% and 34.6% for the 'low' expression and 3.3% and 3.9% for the 'high' expression groups, respectively. Median time of remission for both miR-744 and let-7e was approximately 11 months for the 'low' expression and approximately 47 months for the 'high' expression groups of myeloma patients These data demonstrate that expression patterns of circulating microRNAs are altered in multiple myeloma and monoclonal gammopathy of undetermined significance and miR-744 with let-7e are associated with survival of myeloma patients. PMID- 24241496 TI - Simultaneous Soft Sensing of Tissue Contact Angle and Force for Millimeter-scale Medical Robots. AB - A novel robotic sensor is proposed to measure both the contact angle and the force acting between the tip of a surgical robot and soft tissue. The sensor is manufactured using a planar lithography process that generates microchannels that are subsequently filled with a conductive liquid. The planar geometry is then molded onto a hemispherical plastic scaffolding in a geometric configuration enabling estimation of the contact angle (angle between robot tip tangent and tissue surface normal) by the rotation of the sensor around its roll axis. Contact force can also be estimated by monitoring the changes in resistance in each microchannel. Bench top experimental results indicate that, on average, the sensor can estimate the angle of contact to within +/-2 degrees and the contact force to within +/-5.3 g. PMID- 24241495 TI - The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial. AB - In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate immune response, and subclinical organ injury during experimental human endotoxemia. The administration of iron sucrose induced a profound increase in plasma malondialdehyde 1 h after administration (433+/-37% of baseline; P<0.0001), but did not potentiate the endotoxemia-induced increase in malondialdehyde, as was seen 3 h after endotoxin administration in the placebo group (P=0.34) and the iron chelation group (P=0.008). Endotoxemia resulted in an initial increase in serum iron levels and transferrin saturation that was accompanied by an increase in labile plasma iron, especially when transferrin saturation reached levels above 90%. Thereafter, serum iron decreased to 51.6+/-9.7% of baseline at T=8 h in the placebo group versus 84+/-15% and 60.4+/-8.9% of baseline at 24 h in the groups treated with iron sucrose and deferasirox, respectively. No significant differences in the endotoxemia-induced cytokine response (TNF-alpha, IL-6, IL-10 and IL-1RA), subclinical vascular injury and kidney injury were observed between groups. However, vascular reactivity to noradrenalin was impaired in the 6 subjects in whom labile plasma iron was elevated during endotoxemia as opposed to those in whom no labile plasma iron was detected (P=0.029). In conclusion, a single dose of iron sucrose does not affect the innate immune response in a model of experimental human endotoxemia, but may impair vascular reactivity when labile plasma iron is formed. (Clinicaltrials.gov identifier:01349699). PMID- 24241497 TI - Available and affordable mental healthcare. PMID- 24241499 TI - Mental health practitioners' use and attitudes regarding the Internet and social media. AB - OBJECTIVE: Internet-based technologies, such as email and social media, are being increasingly used by mental health providers. The authors created a survey to better understand mental health providers' practices and attitudes regarding these platforms. METHODS: Psychiatrists and psychologists at Columbia and the New York State Psychiatric Institute completed a 24-item multiple choice and free text survey about their use of and attitudes toward Internet technologies. RESULTS: One hundred and thirty faculty responded to the survey: 70% percent of respondents reported that they were somewhat or more familiar with social media; 20% reported that they sometimes or often searched for information about their patients online; and 60% said that searching for patients online could have a positive role in ongoing psychiatric care. Respondents with fewer years of practice were significantly more likely to use Facebook/Google Plus, texting, and instant messenger in their personal lives, while those with more years of practice were more likely to use Skype professionally. Practitioners who worked in hospital settings were more likely to search online for information about their patients. Practitioners working in outpatient clinics, private practices, and research settings were more likely to use websites, email, and Skype in their practices. CONCLUSIONS: Mental health care professionals are starting to incorporate Internet technologies into their professional lives, but they remain divided on the ethics and utility of using these technologies in clinical care. There appear to be differences in practices and attitudes toward the Internet among clinicians with different levels of experience and in different practice settings. PMID- 24241498 TI - Perinatal antidepressant use: understanding women's preferences and concerns. AB - Perinatal depression is prevalent and linked with a host of adverse consequences for women and newborns. Rates of engagement in depression treatment are, however, strikingly low among pregnant and postpartum women, with the majority of affected women receiving no mental health treatment. Research indicates that perinatal women are extremely reluctant to take antidepressant medications, yet the nature of women's concerns and treatment decision- making patterns have not been well documented. Developing a clearer understanding of women's treatment preferences and behaviors may help identify solutions to the under-treatment of perinatal depression. In this mixed methods study, we conducted in-depth interviews with 61 pregnant women, approximately half of whom were experiencing clinical levels of depression. In addition to assessing psychiatric diagnoses, symptoms, and functional impairment, we conducted qualitative interviews addressing women's preferences for depression treatment, concerns, and decision-making patterns. Consistent with prior reports, women were significantly more likely to voice a preference for non-pharmacologic depression treatments, as opposed to antidepressant medications. Many depressed women reported a great degree of uncertainty regarding how to treat their depression, and those with more severe depression symptoms were more likely to endorse decisional conflict. Analysis of qualitative comments yielded detailed information about the nature of women's concerns and preferences related to use of antidepressant medications and other aspects of treatment engagement. We discuss findings in the context of improving patient-centered care for perinatal depression. PMID- 24241501 TI - Can personality traits predict the future development of heart disease in hospitalized psychiatric veterans? AB - OBJECTIVE: To examine which personality traits are associated with the new onset of chronic coronary heart disease (CHD) in psychiatric inpatients within 16 years after their initial evaluation. We theorized that personality measures of depression, anxiety, hostility, social isolation, and substance abuse would predict CHD development in psychiatric inpatients. METHOD: We used a longitudinal database of psychological test data from 349 Veterans first admitted to a psychiatric unit between October 1, 1983, and September 30, 1987. Veterans Affairs and national databases were assessed to determine the development of new onset chronic CHD over the intervening 16-year period. RESULTS: New-onset CHD developed in 154 of the 349 (44.1%) subjects. Thirty-one psychometric variables from five personality tests significantly predicted the development of CHD. We performed a factor analysis of these variables because they overlapped and four factors emerged, with positive adaptive functioning the only significant factor (OR=0.798, p=0.038). CONCLUSION: These results support previous research linking personality traits to the development of CHD, extending this association to a population of psychiatric inpatients. Compilation of these personality measures showed that 31 overlapping psychometric variables predicted those Veterans who developed a diagnosis of heart disease within 16 years after their initial psychiatric hospitalization. Our results suggest that personality variables measuring positive adaptive functioning are associated with a reduced risk of developing chronic CHD. PMID- 24241502 TI - Outliers on the dose-response curve: if the problem is not concentration, then what? AB - This column addresses the two primary reasons some patients do not respond as usual to a medication. Such patients may not benefit either because they are uniquely sensitive to the adverse effects of the drug and/or because the drug does not work on the correct mechanism of action to treat the illness. This column explains and reviews these concepts and provides a rationale for using such information prospectively to increase the likelihood of an optimal outcome with the prescribed treatment. PMID- 24241500 TI - Use of mental health services in transition age youth with bipolar disorder. AB - OBJECTIVES: There is concern that treatment of serious mental illness in the United States declines precipitously following legal emancipation at age 18 years and transition from specialty youth clinical settings. We examined age transition effects on treatment utilization in a sample of youth with bipolar disorder. METHODS: Youth with bipolar disorder (N=413) 7-18 years of age were assessed approximately twice per year (mean interval 8.2 months) for at least 4 years. Annual use of any individual, group, and family therapy, psychopharmacology visits, and hospitalization at each year of age, and monthly use from ages 17 through 19 years, were examined. The effect of age transition to 18 years on monthly visit probability was tested in the subsample with observed transitions (n=204). Putative sociodemographic moderators and the influence of clinical course were assessed. RESULTS: Visit probabilities for the most common modalities psychopharmacology, individual psychotherapy, and home-based care- generally fell from childhood to young adulthood. For example, the annual probability of at least one psychopharmacology visit was 97% at age 8, 75% at age 17, 60% at age 19, and 46% by age 22. Treatment probabilities fell in transitionage youth from age 17 through 19, but a specific transition effect at age 18 was not found. Declines did not vary based on sociodemographic characteristics and were not explained by changing severity of the bipolar illness or functioning. CONCLUSIONS: Mental health treatment declined with age in this sample of youth with bipolar disorder, but reductions were not concentrated during or after the transition to age 18 years. Declines were unrelated to symptom severity or impairment. PMID- 24241503 TI - Psyche--the meeting of mind and soul: current psychoanalytic views on the mental representation of god. AB - The author presents an overview of two contemporary, related psychoanalytic perspectives on religious phenomena. Based on data from systematic interviews, Ana-Maria Rizzuto explores the way the human mind forms the idea of God as it evolves through the various stages of childhood and adult development. The object representation of God is greatly influenced by the mental representations of mother, father, and other important adults in the child's life. Object relations theory and the writings of Winnicott play an important role in these concepts. William Meissner, a Jesuit priest as well as a psychoanalyst, addresses Freud's views of religious belief as an illusion, or when accepted with certainty as real, as a delusion. Instead, Meissner sees religious belief as a developmental process that resides in the mental realm of transitional phenomena where spirituality, creativity, appreciation of beauty, transcendental states, play, and the psychoanalytic process itself also take place. In psychoanalytic treatment, religious phenomena are not exempt from exploration and understanding, perhaps resulting in more mature development of object representations, ego functions, and the superego functions of conscience and ego ideal as well as more mature religious life. PMID- 24241504 TI - Frontotemporal dementia mimicking bipolar disorder. AB - Frontotemporal dementia is a cause of behavioral disturbance that usually appears in individuals between 45 and 65 years of age. The authors present the case of a 65-year-old patient that illustrates how frontotemporal dementia can be misdiagnosed based on a behavioral pattern that suggests the presence of a primary mood disorder. Early accurate diagnosis of frontotemporal dementia and subsequent supportive measures can allow patients and families to make important decisions about business and legal affairs and how to spend remaining leisure time in the most meaningful and enjoyable way possible. PMID- 24241505 TI - Undiagnosed normal pressure hydrocephalus as a cause of diagnostic difficulties in a patient with depression. AB - Normal pressure hydrocephalus is characterized by gait disturbance, urinary incontinence, cognitive impairment, and the finding of ventriculomegaly in imaging studies. It is one of the causes of potentially reversible dementia. The authors present the case of a patient with depression complicated by hydrocephalus. The combination of symptoms led to a delay in proper diagnosis and treatment. PMID- 24241506 TI - Commentary on cognitive and psychiatric symptoms associated with normal pressure hydrocephalus and frontotemporal dementia. AB - Normal pressure hydrocephalus, a reversible cause of dementia, and frontotemporal dementia, an irreversible process, may present with or complicate psychiatric illness. Recognition of these neurological disorders in patients presenting with behavioral symptoms affects key treatment decisions and prognosis. PMID- 24241508 TI - Effect of a stroke-specific follow-up care model on the quality of life of stroke patients and caregivers: A controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of a stroke-specific follow-up care model on quality of life for stroke patients, being discharged home, and their caregivers. DESIGN: A non-randomized, controlled trial, comparing an intervention group with a control group (usual care). SUBJECTS: Stroke patients and their caregivers. METHODS: Intervention involved 5 home visits by a stroke care coordinator over a period of 18 months, using a structured assessment tool. Outcome measures were conducted at baseline (T0) and every 6 months thereafter (T6, T12 and T18) in the domains of quality of life (primary), activities of daily living, social activities, depression, anxiety and caregiver strain. RESULTS: The intervention group (n = 62) had significantly increased its social activities after 18 months, whereas the control group (n = 55) showed significantly decreased levels of social activities. In the first 6 months, levels of depression decreased significantly in caregivers of the intervention group. No differences were found for quality of life and the other outcome measures. CONCLUSION: The intervention was not effective in improving quality of life, but was effective in improving levels of social activities. The intervention may have focussed too much on screening for stroke-related problems and not as much on adequate follow-up care and referral. PMID- 24241507 TI - Rare variants in LRRK1 and Parkinson's disease. AB - Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow-up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance. PMID- 24241509 TI - Exocytosis in non-plasmolyzed and plasmolyzed tobacco pollen tubes : A freeze fracture study. AB - Exocytosis occurring during deposition of secondary wall material was studied by freeze-fracturing ultrarapidly frozen non-plasmolyzed and plasmolyzed tobacco pollen tubes. The secondary wall of tobacco pollen tubes shows a random orientation of microfibrils. This was observed directly on fractures through the tube wall and indirectly as imprints of microfibrils on fracture faces of the plasma membrane of non-plasmolyzed tubes. About half of the plasmatic fracture faces from non-plasmolyzed and plasmolyzed pollen tubes carried hexagonal arrays of intramembraneous particles in between randomly distributed particles. Deposition of secondary wall material was often accompanied by an undulated plasma membrane and the presence of membrane-bound vesicles in invaginations of the plasma membrane, between the plasma membrane and secondary wall and especially in plasmolyzed tubes-within the secondary wall of tube flanks and wall cap. The findings are discussed in connection with published schemes of membrane behaviour during exocytosis. PMID- 24241510 TI - The role of bacterial attachment in the transformation of cell-wall-regenerating tobacco protoplasts by Agrobacterium tumefaciens. AB - The presence of a newly formed primary cell wall was shown to be required for attachment and subsequent transformation of tobacco leaf protoplasts by Agrobacterium tumefaciens in cocultivation experiments. In these experiments both protoplasts at different stages after their isolation and cell-wall inhibitors were used. The specificity of Agrobacterium attachment was shown by using other kinds of bacteria that did not attach. By diminishing the concentration of divalent cations using ethylenediaminetetraacetic acid, neither attachment nor transformation was found; however, when more specifically the Ca(2+)concentration was lowered by ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, both phenomena occurred. Commercial lectins had no effect on binding, but this observation does not exclude the involvement of other lectins. Protoplasts isolated from various crown-gall callus tissues also developed binding sites, but when they were at the stage of dividing cells, attachment of agrobacteria was no longer observed. In this respect, cells from protoplasts of normal tobacco leaves behaved differently. Even 16 d after protoplast isolation, the dividing cells were still able to bind A. tumefaciens, while transformation was not detected. For transformation of 3-d-old tobacco protoplasts, a minimal co-cultivation period of 24 h was required, while optimal attachment took place within 5 h. It is concluded that the primary cell wall was sufficiently well formed that certain functional receptor molecules were available for attachment of Agrobacterium as the first step of a multistep process leading to the transformation of cells. The expression of bacterial functions required for attachment, moreover, was independent of the presence of Ti-plasmid. PMID- 24241511 TI - Cortical microtubular lattices: Absent from mature mesophyll and necessary for cell division? AB - Using immunofluorescence microscopy, the cortical microtubular net which is regularly present in cells of young, growing tissue is shown to be absent, or largely reduced, in mature mesophyll cells of Nicotiana plumbaginifolia Viv., N. tabacum L., Petunia hybrida Hort. and Brassica napus L. The onset of division in protoplasts isolated from these fully differentiated tissues is preceded by a period of dedifferentiation. One of the early events during dedifferentiation, as shown for N. plumbaginifolia, is the re-establishment of a net of cortical microtubules, prior to spindle formation. These findings indicate that the presence of the cortical microtubular lattice is a prerequisite for protoplast division. Cell-wall regeneration, which also must precede division, occurs simultaneously with the formation of the lattice. However, the cortical microtubules seem to not exert any influence on the orientation of the microfibrils. PMID- 24241512 TI - The control of seed germination in Trollius ledebouri: The breaking of dormancy. AB - Seeds of Trollius ledebouri exhibit low germination when maintained on moistened filter paper. Dormancy can be overcome by the application of gibberellins A4+A7 or by testa removal. Germination is characterised by a change in the anatomy of the seed and by specific alterations in the protein complement of the endosperm tissue. These anatomical and biochemical changes are also exhibited by isolated endosperm tissue maintained in the absence of the embryo. The observations described are discussed in relation to the interaction between the endosperm and the embryo in the control of seed germination in T. ledebouri. PMID- 24241513 TI - The control of seed germination in Trollius ledebouri A model of seed dormancy. AB - Treatment of Trollius ledebouri seeds with gibberellins A4+A7 promotes germination. The efficacy of the treatment is dependent upon the duration of imbibition in distilled water prior to GA4+7 application. 'Presoaking' increases both the final percentage germination attained and also its rate of achievement. No presoaking effect is exhibited by seeds induced to germinate by testa removal in the absence of GA4+7. Active washing of Trollius seeds enhances the presoaking effect and the eluent from washed seeds is inhibitory to germination. The results support the hypothesis that the presoaking effect exhibited by Trollius is the result of the leaching of a germination inhibitor from the seeds which is antagonistic to GA4+7. Additionally, treatment of Trollius seeds with the gibberellin-biosynthesis inhibitor (2-chloroethyl)-trimethylammonium chloride (CCC) prior to testa removal retards germination. The inhibitory effect of CCC on germination is overcome by GA4+7. Although CCC inhibits embryo growth during the presoaking of intact seeds, it does not affect the increased sensitivity of presoaked seeds to GA4+7. Therefore, although endogenous gibberellins may be involved in the germination process, they do not contribute to the presoaking phenomenon. The expansion of isolated endosperm tissue is not affected by CCC. However, the chemical markedly inhibits endosperm expansion in intact seeds and implicates the embryo as both the site of production of the germination inhibitor and of gibberellin. These results are discussed in relation to previous studies and a model is presented to account for the characteristics of germination in Trollius. PMID- 24241514 TI - Immuno-gold localization of glutamine synthetase in a nitrogen-fixing cyanobacterium (Anabaena cylindrica). AB - Localization of glutamine synthetase in thin sections of nitrogen-fixing Anabaena cylindrica was performed using immuno-gold/transmission electronmicroscopy. The enzyme was present in all of the three cell types possible; vegetative cells, heterocysts and akinetes. The specific gold label was always more pronounced in heterocysts compared with vegetative cells, and showed a uniform distribution in all three types. No specific label was associated with subcellular inclusions such as carboxysomes, cyanophycin granules and polyphosphate granules. When anti glutamine synthetase antiserum was omitted, no label was observed. PMID- 24241515 TI - Water droplets in intercellular spaces of barley leaves examined by low temperature scanning electron microscopy. AB - Low-temperature scanning electron microscopy was used to examine fracture faces in leaf blades taken from well-watered or drought-stressed barley (Hordeum vulgare L. cv. Mazurka) seedlings. The leaf blades were freeze-fixed while hydrated and were examined with or without gold-coating. There were 'droplets' (with a smooth surface at the resolution achieved) on the surface of cell walls in leaf blades (0.91 g(-1) water content) from well-watered seedlings grown in an environment of 67% relative humidity. These were mainly on the vascular bundle sheath, the guard and subsidiary cells, and on some mesophyll cells around the substomatal cavity and between the stoma and vascular bundle. The droplets occurred, more abundantly, in the same places in seedlings from 100% relative humidity. They occurred on a few guard cells from wilting leaf blades (0.81 g.g( 1) water content) and were absent from severely drought-stressed leaf blades (0.15 g.g(-1) water content). The droplets sublimed at the same moment as both water which was in leaf cells and water which was allowed to condense (after freeze-fixation) on the wall surface. It is suggested that the droplets are aqueous. Their possible origin and importance is discussed. PMID- 24241516 TI - Effects of external pH, fusicoccin and butyrate on the cytoplasmic pH in barley root tips measured by (31)P-nuclear magnetic resonance spectroscopy. AB - (31)P-Nuclear magnetic resonance spectroscopy was used to measure the cytoplasmic pH (pHc) in barley (Hordeum vulgare L.) root tips. As the external pH was raised from 4-10, pHc was found to increase from 7.44 to 7.75. The sensitivity of pHc to changes in external pH decreased with increasing external pH. Metabolic inhibition by sodium azide caused pHc to fall by 0.3 units. Addition of 10 mM butyrate resulted in a gradual decline in pHc, by approx. 0.3 units over 90 min. At a concentration of 1 mM, butyrate had no effect on pHc even after 2 h. Fusicoccin caused pHc to rise by 0.1-0.2 units. In maize (Zea mays L.) root tips, pHc was shown to have a similar sensitivity to fusicoccin. The results are discussed in relation to the regulation of pHc and the possible role of pHc in determining transmembrane electrical potential differences. PMID- 24241517 TI - Evidence for phytochrome involvement in light-mediated stomatal movement in Phaseolus vulgaris L. AB - Observations made with primary leaves of Phaseolus vulgaris L. demonstrated that phytochrome modulates light-induced stomatal movement. Removal of the far-red absorbing form of the pigment (Pfr) with far-red (FR) radiation decreased the time required by the stomata to reach maximal opening following a dark-to-light transition; this effect of FR was fully reversible with red. Removal of Pfr with FR also decreased the time required to reach maximal closure following a light-to dark transition, and the rate of closure was dependent on the final irradiation treatment before darkness. No evidence was found for phytochrome involvement in determining stomatal aperture under constant conditions of either darkness of light. PMID- 24241518 TI - A comparative study of metabolite levels in plant leaf material in the dark. AB - Metabolite levels have been compared in the dark and during photosynthesis in leaves and protoplasts from spinach, pea, wheat and barley. In protoplasts the subcellular distribution was also studied. The levels of triose phosphates and sugar bisphosphates were high in the light and low in the dark. The hexose phosphates and 3-phosphoglycerate levels in the dark were very variable depending on the plant material. In most conditions, hexose phosphates and triose phosphates were mainly in the extrachloroplast compartment, while 3 phosphoglycerate and the sugar bisphosphates were mainly in the chloroplast compartment. Leaves always had a very low triose phosphate: 3-phosphoglycerate ratio in the dark, but in protoplasts this ratio was higher. Detailed studies with spinach showed that metabolite levels were very dependent on the availability of carbohydrate in the leaf, particularly starch. Starch mobilisation is not controlled just by the availability of inorganic phosphate and accumulation of phosphorylated intermediates. Hydrolysis of starch may provide precursors for sucrose synthesis while phosphorolysis leads to provision of substrates for respiration. Starch breakdown generates high enough levels of hexose phosphate to support substantial rates of sucrose synthesis in the dark. Respiration is not greatly increased when metabolite levels are high during starch mobilisation. Higher levels of metabolites shorten the length of the induction phase of photosynthesis. PMID- 24241519 TI - Circadian-clock control of protein synthesis and degradation in Gonyaulax polyedra. AB - In growing cultures of the dinoflagellate, Gonyaulax polyedra, total protein synthesis showed a circadian rhythm with a maximum during the phase of the cycle which corresponded to the previous darktime. The maximum coincided with the maximal phase shift of the glow rhythm caused by lower concentrations of the antibiotic anisomycin (Taylor, W., et al., 1982). J. Comp. Physiol. 148 B, 11-25. The dose reponses of inhibition of protein synthesis correlated well with the phase shifting by anisomycin. The amplitude and level of the total-protein synthesis rhythm increased with the growth rate, indicating that the majority of proteins controlled by the circadian clock were cell cycle-dependent. The degradation rate showed the same circadian rhythm as the synthesis rate. Slight variations in uptake and pool size of amino acids were not responsible for the rhythm in the protein-synthesis rate. PMID- 24241520 TI - Photosynthate transport in stems of Phaseolus vulgaris L. treated with gibberellic acid, indole-3-acetic acid or kinetin. : Effects at the site of hormone application. AB - Gibberellic acid (GA3), indole-3-acetic acid (IAA) or kinetin ((6)N furfurylaminopurine) applied to the apical regions of decapitated stems of derooted Phaseolus vulgaris plants, promoted (14)C-photosynthate transport to the site of hormone application. Hormonal promotion of acropetal photosynthate transport was associated with significant increases in the pool size of free space sugars at the hormone-treated region of the stem. The hormone-induced increases in the free-space pool size depended on continued phloem transport in the stem stumps while photosynthate leakage from the sink tissues of the stems was unaffected by the hormone treatments. On the basis of these observations, it is concluded that the increases in the pool size of sugars in the stem free-space results from hormonal action on processes that determine rates of sugar unloading from the sieve element-companion cell (se-cc) complexes. Furthermore, since loading of the se-cc complexes in the stem stumps was stimulated by GA3 and IAA and unaffected by kinetin applied at the loading site, hormonal effects on net unloading from the se-cc complexes must be caused by alterations in the efflux component. For winter-grown plants, it was found that predicted increases in sugar transfer through the stem free-space from the se-cc complexes to the sink tissues could account for the observed hormonal stimulation of photosynthate transport. In contrast, for summer-grown plants the higher sugar concentrations in the stem free-space of control plants approached saturation for the sugar accumulation process. This caused an attenuation of the responsiveness of sugar accumulation by the stem sink tissues to hormone-induced increases in the pool size of sugars in the stem free-space. On this basis it is proposed that the bulk of photosynthates may move radially from the se-cc complexes through the stem symplast of summer-grown plants. PMID- 24241521 TI - Effects of drought on photosynthesis, chlorophyll fluorescence and photoinhibition susceptibility in intact willow leaves. AB - Plants from clonal cuttings of Salix sp. were subjected to a drying cycle of 10 d in a controlled environment. Gas exchange and fluorescence emission were measured on attached leaves. The light-saturated photosynthetic CO2 uptake became progressively inhibited with decreased leaf water potential both at high, and especially, at low intercellular CO2 pressure. The maximal quantum yield of CO2 uptake was more resistant. The inhibition of light-saturated CO2 uptake at leaf water potentials around-10 bar, measured at a natural ambient CO2 concentration, was equally attributable to stomatal and non-stomatal factors, but the further inhibition below this water-stress level was caused solely by non-stomatal factors. The kinetics of fluorescence emission was changed at severe water stress; the slow secondary oscillations of the induction curve were attenuated, and this probably indicates perturbations in the carbon reduction cycle. The influence of light level during the drought period was also studied. Provided the leaves were properly light-acclimated, drought at high and low light levels produced essentially the same effects on photosynthesis. However, low-light acclimated leaves became more susceptible to photoinhibitory treatment under severe water stress, as compared with well-watered conditions. PMID- 24241522 TI - Monoclonal antibodies to plant growth regulators. II. Indole-3-acetic acid. AB - The production and characterization of high-affinity monoclonal antibodies suitable for the radio- and enzymeimmunoassay of the endogenous plant growth regulator, indole-3-acetic acid (IAA), is reported. Hybridomas were produced by fusion of NS 1 myeloma cells with spleen cells from Balb/c mice immunized with IAA-bovine serum albumin conjugates. From an initial collection of 158 wells containing cells secreting monoclonal antibodies against IAA, seven were used to derive cell clones. Three of these are described here. They secrete immunoglobulin (IgG2a or IgG2b) of high affinity and specificity for IAA methyl ester and can be used to quantite picogram amounts of this compound in plant extracts by radio- and enzymeimmunoassay. PMID- 24241523 TI - Phosphoproteins and protein-kinase activity in isolated envelopes of pea (Pisum sativum L.) chloroplasts. AB - A protein kinase was found in envelope membranes of purified pea (Pisum sativum L.) chloroplasts. Separation of the two envelope membranes showed that most of the enzyme activity was localized in the outer envelope. The kinase was activated by Mg(2+) and inhibited by ADP and pyrophosphate. It showed no response to changes in pH in the physiological range (pH 7-8) or conventional protein substrates. Up to ten phosphorylated proteins could be detected in the envelope membrane fraction. The molecular weights of these proteins, as determined by polyacrylamide-gel electrophoresis were: two proteins higher than 145 kDa, 97, 86, 62, 55, 46, 34 and 14 kDa. The 86-kDa band being the most pronounced. Experiments with separated inner and outer envelopes showed that most labeled proteins are also localized in the outer-envelope fraction. The results indicate a major function of the outer envelope in the communication between the chloroplast and the parent cell. PMID- 24241524 TI - Detoxification of N-(phosphonoacetyl)-L-aspartate by carrot cells in suspension culture. AB - In bacterial and mammalian cells, N-(phosphonoacetyl)-L-aspartate (PALA) suppresses growth by strongly inhibiting aspartate transcarbamoylase (ATCase; EC 2.1.3.2), a key enzyme of the pyrimidine biosynthetic pathway. At a concentration that would suppress growth in mammalian or bacterial cells, and that is nearly a million-fold greater than the inhibition constant (K i ) for ATCase in carrot (Daucus carota) seedling extracts, PALA does not suppress growth of carrot cells in suspension culture. To study this anomaly an assay based on the inhibition of wheat (Triticum vulgare) ATCase (K i =2 nM) was developed. Using this assay it was found that PALA is detoxified relatively rapidly by low inocula of carrot cells. The detoxification product accumulates in the extracellular fluid although the enzyme(s) responsible is intracellular or in the cell wall. The PALA detoxifying activity can be detected at all stages of the growth cycle in culture, but reaches a maximum early in the exponential phase of growth. Cells that were repeatedly subcultured into media initially containing 1 mM PALA had the same low level of ATCase activity as control cells; there was no evidence of the amplification of the gene for this enzyme, such as occurs in mammalian cells upon repeated exposure to the drug. PMID- 24241525 TI - Changes in the levels of wheat- and barley-germ agglutinin during embryogenesis in vivo, in vitro and during germination. AB - Radioimmunoassay has been used to measure levels of wheat-germ agglutinin and barley-germ agglutinin during embryogenesis and germination. The two lectins exhibited similar patterns of accumulation during grain maturation in vivo and both decreased to low levels after imbibition of harvest-ripe grains for 3 d. Precocious germination of immature wheat and barley embryos excised and cultured in vitro could be prevented either by inclusion of abscisic acid or mannitol in the culture medium. Changes in the level of wheat-germ agglutinin induced by in vitro culture depended on the maturation stage of the embryo. No direct correlation was found between application of exogenous abscisic acid and accumulation of the lectin. PMID- 24241526 TI - Photosynthesis and ribulose-1,5-bisphosphate carboxylase/oxygenase in rice leaves from emergence through senescence. Quantitative analysis by carboxylation/oxygenation and regeneration of ribulose 1,5-bisphosphate. AB - Changes in gas-exchange rates during the life span of the leaves of rice (Oryza sativa L.) were analyzed quantitatively by measuring changes in the carboxylation/oxygenation and regeneration of ribulose 1,5-bisphosphate (RuBP) at photon fluence rates of 2000 (saturating) and 500 (subsaturating) MUmol quanta.m( 2).s(-1) under ambient air conditions. The RuBP levels were always higher than the active-site concentrations of RuBP carboxylase (EC 4.1.1.39), irrespective of the irradiance supplied. Analysis of the CO2-assimilation rate as a function of intercellular CO2 concentration indicated that RuBP regeneration does not limit CO2 assimilation. The estimated RuBP-carboxylase/oxygenase activity in vivo was linearly correlated to the rate of CO2 assimilation at each level of irradiance. This enzyme activity was just enough to account for the rate of CO2 assimilation at the saturating irradiance and was 35% more than the rate of CO2 assimilation at the subsaturating irradiance. Analysis of the assimilation rate at subsaturating irradiance as a function of intercellular CO2 concentration indicated that a limitation caused by enzyme activation comes into play. The results indicate that the rate of CO2 assimilation in rice leaves under ambient air conditions is limited during their entire life span by the RuBP carboxylation/oxygenation capacity. PMID- 24241527 TI - Optimization of the biotransformation of L-tyrosine into L-dihydroxyphenylalanine (DOPA) by alginate-entrapped cells of Mucuna pruriens. AB - The optimization of the biotransformation of L-tyrosine into L dihydroxyphenylalanine (DOPA), and of formyl-tyrosine into formyl-DOPA by alginate-entrapped cells of Mucuna pruriens is reported. This optimization is discussed in terms of parameters that are relevant for the entrapped cell system (charge of the beads with cells, bead diameter, permeation of the cells) and some parameters that are relevant for the enzymatic transformation (pH, pO2, concentration of ascorbate). The optimization experiments resulted in the description of a biotransformation system which operates at a constant redox potential. With this transformation system a transformation efficiency of 70% could be obtained, at a biotransformation-rate of 435 MUmol.h(-1).g(-1) (DW of cells) at a substrate concentration of 19 mM. PMID- 24241528 TI - Cytokinin contents and specific characteristics of tissue strains from three sexual genotypes of Mercurialis annua : Evidence for sex-gene involvement at callus-tissue level. AB - Analyses of the endogenous cytokinin contents of established tissue strains of Mercurialis annua are reported. The strains were derived from three individuals (strong male, weak male, female), differing by one of the three genes determining sex. The data are compared with the endogenous cytokinins of male and female shoot apices. Tissue strains are characterized by the disappearance of natural cytokinin metabolites in the female; in both males, Delta(2)-isopentenyl adenosine and only trans-ribosylzeatin exist but in different quantities. Benzyladenine and ribosylbenzyladenine were identified in the three strains but the quantities also differed as a function of the genotype. The marked differences in cytokinin metabolism of tissue strains indicate that sex genes continue to function in the dedifferentiated state. Each strain also exhibited persistent morphological and histological characteristics, and a different sensitivity to the withdrawal of 2-4-dichlorophenoxyacetic acid or benzyladenine from the medium. Each had a specific and characteristic effect on the organogenesis of nodes cultivated in close proximity to callus pieces. These data complement the above results and show that sex genes act at the callus-tissue level. The possibility that these genes act at the early stages of embryogenesis of male and female individuals is also discussed. PMID- 24241529 TI - Erratum. PMID- 24241530 TI - Reproductive phenology of a food-hoarding mast-seed consumer: resource- and density-dependent benefits of early breeding in red squirrels. AB - The production of offspring by vertebrates is often timed to coincide with the annual peak in resource availability. However, capital breeders can extend the energetic benefits of a resource pulse by storing food or fat, thus relaxing the need for synchrony between energy supply and demand. Food-hoarding red squirrels (Tamiasciurus hudsonicus) breeding in the boreal forest are reliant on cones from a masting conifer for their nutrition, yet lactation is typically completed before the annual crop of cones is available for consumption such that peaks in energy supply and demand are not synchronized. We investigated the phenological response of red squirrels to annual variation in environmental conditions over a 20-year span and examined how intra- and inter-annual variation in the timing of reproduction affected offspring recruitment. Reproductive phenology was strongly affected by past resource availability with offspring born earlier in years following large cone crops, presumably because this affected the amount of capital available for reproduction. Early breeders had higher offspring survival and were more likely to renest following early litter loss when population density was high, perhaps because late-born offspring are less competitive in obtaining a territory when vacancies are limited. Early breeders were also more likely to renest after successfully weaning their first litter, but renesting predominantly occurred during mast years. Because of their increased propensity to renest and the higher survival rates of their offspring, early breeders contribute more recruits to the population but the advantage of early breeding depends on population density and resource availability. PMID- 24241532 TI - Duodenal-jejunal bypass and jejunectomy improve insulin sensitivity in Goto Kakizaki diabetic rats without changes in incretins or insulin secretion. AB - Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity (SI). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess SI. SI improved after DJB (SI = 1.14 +/- 0.32 * 10(-4) min(-1) ? pM( 1)) and jejunectomy (SI = 0.80 +/- 0.14 * 10(-4) min(-1) ? pM(-1)), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized SI in diabetic rats as shown by SI levels equivalent to those of Wistar rats (SI = 1.01 +/- 0.06 * 10(-4) min(-1) ? pM(-1); P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on SI, therefore contributing to the control of diabetes after gastric bypass surgery. PMID- 24241531 TI - Influence of differentially expressed genes from suicide post-mortem study on personality traits as endophenotypes on healthy subjects and suicide attempters. AB - Although a genetic contribution to the complex aetiology of suicidal behaviour has been suggested since many years, the attempt to identify specific genes related to suicide has led to contrasting results. In a post-mortem study on suicide, we previously detected several differentially expressed genes which, however, have not been subsequently associated with suicidal behaviour, or only nominally. Therefore, personality traits may represent good intermediate endophenotypes. Our primary aim was to investigate the potential modulation of several single-nucleotide polymorphisms (SNPs) of the same previously investigated genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) on personality traits, as measured with the Temperament and Character Inventory (TCI), in a German sample composed of 287 healthy subjects (males: 123, 42.9 %; mean age: 45.2 +/- 14.9 years) and in 111 psychiatric patients who attempted suicide (males: 43, 38.6 %; mean age: 39.2 +/- 13.6 years). Multivariate analysis of covariance was used to test possible influence of single SNPs on TCI scores. Genotypic, allelic and haplotypic analyses have been performed. Controlling for sex, age and educational level, genotypic analyses showed a modulation of EFEMP1 rs960993 and rs2903838 polymorphisms on both harm avoidance and self-directedness in healthy subjects. Interestingly, we could replicate these associations in haploblocks within controls (p < 0.0001) and in the independent sample of suicide attempters for harm avoidance (p < 0.00001), a phenotype highly associated with suicidal behaviour. This study suggests that EFEMP1 SNPs, never investigated in association with suicidal behaviour and related personality, could be involved in its modulation in healthy subjects as well as in suicide attempters. PMID- 24241533 TI - Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass. AB - Roux-en-Y gastric bypass (RYGB) improves glycemic control within days after surgery, and changes in insulin sensitivity and beta-cell function are likely to be involved. We studied 10 obese patients with type 2 diabetes (T2D) and 10 obese glucose-tolerant subjects before and 1 week, 3 months, and 1 year after RYGB. Participants were included after a preoperative diet-induced total weight loss of -9.2 +/- 1.2%. Hepatic and peripheral insulin sensitivity were assessed using the hyperinsulinemic- euglycemic clamp combined with the glucose tracer technique, and beta-cell function was evaluated in response to an intravenous glucose glucagon challenge as well as an oral glucose load. Within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity, and increased insulin clearance, highlighting the liver as an important organ responsible for early effects on glucose metabolism after surgery. Insulin mediated glucose disposal and suppression of fatty acids did not improve immediately after surgery but increased at 3 months and 1 year; this increase likely was related to the reduction in body weight. Insulin secretion increased after RYGB only in patients with T2D and only in response to oral glucose, underscoring the importance of the changed gut anatomy. PMID- 24241534 TI - Adipocyte spliced form of X-box-binding protein 1 promotes adiponectin multimerization and systemic glucose homeostasis. AB - The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. In this study, we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of high-molecular-weight adiponectin and, indeed, is adiponectin-dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription, likely through a direct regulation of the expression of several ER chaperones involved in adiponectin maturation, including glucose-regulated protein 78 kDa, protein disulfide isomerase family A, member 6, ER protein 44, and disulfide bond oxidoreductase A-like protein. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. PMID- 24241538 TI - The characterization of herbicide tolerant plants in Brassica napus L. after in vitro selection of microspores and protoplasts. AB - Brassica napus L.(cv Topas) plants tolerant to chlorsulfuron (CS) were isolated after selection experiments utilizing microspores and haploid protoplasts. The first microspore-derived plant (M-37,) was CS tolerant, haploid and sterile. Normal plant morphology and fertility was restored after colchicine doubling. A CS tolerant plant was also selected from protoplasts (P-26) isolated from microspore-derived embryo tissue and grown on medium containing CS. P-26 was aneuploid, CS tolerant and had very low fertility. The two selected lines produced selfed progeny which were tolerant to from 10-100 times the CS levels of the corresponding Topas plants. Microspores and protoplasts derived from the selfed plants were also CS tolerant. The segregation pattern for CS tolerance from reciprocally crossed progeny of M-37 and Topas was consistent with a semi dominant nuclear mode of inheritance. Biochemical analysis of the two mutants indicated that the microspore-derived mutant and F1 crosses contained an altered acetohydroxyacid synthase (AHAS) enzyme, while the AHAS activity of the protoplast mutant was similar to Topas. Selfed seed from the M-37 plants have provided tolerance to CS in both greenhouse and field tests. S1 plants from a second microspore selected mutant (M-42) have tolerated 30 g/ha of CS in greenhouse tests. The two single-celled selection systems are discussed and the microspore selection system highlighted as a new method for in vitro selection. PMID- 24241535 TI - Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. AB - Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism. PMID- 24241536 TI - High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias. AB - To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases. PMID- 24241539 TI - Genetic transformation of cauliflower (Brassica oleracea L. var. Botrytis) by Agrobacterium rhizogenes. AB - Cauliflower plantlets were inoculated with different Agrobacterium rhizogenes strains. Numerous hairy roots were induced on cauliflower hypocotyls by agropine type strains. Fewer roots were obtained with mannopine-type strains. In vitro cultures were established both from normal and hairy roots. Plant regeneration occured spontaneously from normal and transformed roots. Regenerated plants contained the same opines (if present) as root cultures. Some mannopine-positive regenerants displayed a modified phenotype. Relationships between phenotype, opine content, T-DNA content and/or expression are discussed. PMID- 24241540 TI - T-DNA length variability in mannopine hairy root: more than 50 kilobasepairs of pRi T-DNA can integrate in plant cells. AB - Independent carrot (Daucus carota) hairy root lines were established by inoculation of discs taken from the same carrot with Agrobacterium rhizogenes 8196 and A. tumefaciens C58C1(pRi8196) carrying pRi8196. Several lines were compared with respect to T-DNA length. One of them was found to have integrated sequences covering more than 50 kbp of the Ri plasmid. PMID- 24241537 TI - A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. AB - Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes. PMID- 24241541 TI - A rapid method for purification of organelles for DNA isolation: self-generated percoll gradients. AB - Self-generated Percoll gradients have been used for rapid purification of crude chloroplasts and mitochondria, obtained by common differential centrifugation techniques. Such purified organelles were used for isolating DNA from safflower (Carthamus tinctorius L.), carrot (Daucus carota L.), various Solanaceae, and numerous somatic hybrids. The method is simple, has the advantage of not requiring DNase, and is particularly well suited when only limited amounts of aseptically grown shoots are available. As judged by restriction enzyme analyses and chloroplast DNA cloning experiments, the DNAs are of sufficient purity for many molecular biological applications without CsCl gradient purification. PMID- 24241542 TI - Celery transformation by Agrobacterium tumefaciens: cytological and genetic analysis of transgenic plants. AB - Transgenic celery plants were obtained following co-cultivation of petiole explants with Agrobacterlum tumefaciens containing pMON200, a cointegrate vector carrying genes for kanamycin resistance and nopaline synthase. Transformants were selected by ability of callus to grow in the presence of 50mg/l kanamycin. Transformation was confirmed either by the presence of nopaline or by Southern blots. Cytological analysis of 14 transformed plants revealed chromosomal aberrations, both in structure and number. Only 20% of the regenerated plants had the normal karyotype. Kanamycin resistance behaved as a monogenic, dominant trait, segregating in a 3:1 ratio in three families derived from plants with normal karyotypes. PMID- 24241543 TI - Species specific shoot regeneration response of cotyledonary explants of Brassicas. AB - A study of shoot regeneration from cotyledons of three basic diploid species of Brassica, B. campestris (AA), B. nigra (BB), B. oleracea (CC) and their amphidiploids B. juncea (AABB), B. napus (AACC) and B. carinata (BBCC) showed species-specific responses for in vitro shoot regeneration. Analysis of the species mean shoot regeneration response over a range of growth regulator combinations revealed that i) B. campestris is the lowest regenerating species, ii) B. nigra and B. oleracea regenerate with high frequencies, iii) In amphidiploids, the presence of B. campestris component brings down shoot regeneration frequency below the value of B. oleracea in B. napus combination and is additive of the combining genomes in B. juncea combination. In B. carinata regeneration frequencies are less than the parental diploid species, iv) Significant intraspecific genotypic differences were observed for B. nigra and B. oleracea among diploids and B. juncea and B. carinata among amphidiploids, when cotyledons of eighteen genotypes were tested in one growth regulator combination. PMID- 24241544 TI - Isolation and purification of generative cells from fresh pollen of Vicia faba L. AB - A technique named two-step osmotic shock was developed for isolating generative cells (GCs): pollen grains were incubated in 20% sucrose solution and shocked by adding water. This caused the pollen grains to burst and release their contents including GCs. By subsequent filtration and centrifugation the isolated GCs were purified. The viability of GCs before and after purification was confirmed by fluorescein diacetate (FDA) test. This procedure offers a rapid and effective means to obtain living GCs in quantities. PMID- 24241545 TI - Effect of the differentiated or dedifferentiated state of tobacco pith tissue on its behaviour after inoculation with Agrobacterium rhizogenes. AB - The ability of Nicotiana tabacum (cv. Wisconsin 38) pith tissue to give rise to transformed roots after inoculation with Agrobacterium rhizogenes (agropine type strain 1855) has been examined in relation to its state of differentiation. In young plants, all the stem tissues are able to initiate transformed roots while pith of adult plants does not react. Mature pith, composed mostly of polyploid and non-dividing cells, is able to recover susceptibility when placed in vitro on a medium containing auxin and kinetin. The optimal production of transformed roots is obtained after 6-10 days, when proliferating cells redifferentiated "cambial-like" layers and tracheids. The relationships between the inability of fully differentiated pith to give rise to roots and the underlying cell states are discussed. PMID- 24241546 TI - The effect of cadaverine on the formation of anabasine from lysine in hairy root cultures of Nicotiana hesperis. AB - Unlabelled cadaverine did not diminish the incorporation into anabasine of (14)C from L-[U-(14)C] lysine supplied to hairy root cultures of Nicotiana nesperis, despite causing a stimulation of anabasine production. The finding is discussed in the context of previous observations indicating that free cadaverine is not an intermediate in the biosynthesis of anabasine from lysine. PMID- 24241547 TI - Cadmium tolerance in tobacco cell culture and its relevance to temperature stress. AB - Growth of unselected tobacco (Nicotiana tabacum W38) cell suspension cultures was reduced by 50-200 MUM cadmium (Cd) in the culture medium and cells were killed by 400 MUM Cd. Tolerance to Cd was increased either by using rapidly growing cells or by culturing cells at higher densities. Cell lines tolerant to 2 mM Cd were established by progressively elevating levels of Cd in the culture medium. The Cd tolerance was not due to differences in uptake between unselected and Cd-tolerant cell lines, and the tolerance to Cd was not lost during long term culture in the absence of Cd. Cd-tolerant cells also showed higher tolerance to heat shock (37.5 degrees C, 2-8 hours) and cold treatments (4 degrees C, 1-7 days) than the unselected cells. PMID- 24241548 TI - Production, maintenance and plant regeneration from cell suspension cultures of Stevia rebaudiana (Bert.) Bertoni. AB - A method is described for producing and maintaining Stevia rebaudiana suspensions and regeneration of plants from calli derived from cell suspensions. Suspension cultures composed of isolated cells (ca. 10%) and cellular aggregates (5-100 cells) were obtained in 20-30 days by using friable callus as the initial inoculum in liquid media with BA (0.5 mg/l)+2,4-D (1.0 mg/l), and periodic filtering (100-500 MUm sieves) with 6-7 days interval between subcultures. Cultures derived from actively growing calli are mainly diploid (2n=22) whereas those derived from senescent calli showed a wide variation in chromosome number (55-200). Stock cell suspensions which had been maintained for 3 years were plated on basal LS agar medium with BA (0.5 mg/l)+2,4D (0.5 mg/l) to form callus. Calli originating from predominantly 2n cell suspensions when transferred to medium with K (2.0 mg/l)+NAA (0.02 mg/l) were able to form buds. Shoot elongation and further rooting of isolated shoots was better on LS medium devoid of growth regulators. Variation in rooting capacity, plant vigour, morphological characters and chromosome number was found amongst regenerated plants. PMID- 24241549 TI - Substitution analysis of callus induction and plant regeneration from anther culture in wheat (Triticum aestivum L.). AB - The genetic determination of callus induction, total plant regeneration and green plant regeneration from anther culture were studied using a "Chinese Spring"/"Cheyenne" substitution series. All the three characteristics were found to be polygenically determined, but their inheritance was independent from one another. The 7A and 18 chromosomes had a considerable effect on callus induction. In the case of total plant regeneration the most influential chromosome "as the 3A while the 2D chromosome showed a definite influence on green plant regeneration. The interaction between the genetic background of the recipient plant and the substituted chromosome plays an important role in the manifestation of the studied features. PMID- 24241550 TI - Tissue culture of Chrysosplenium americanum and its potential for flavonoid production. AB - Chrysosplenium americanum (Saxifragaceae) accumulates a variety of partially O methylated flavonol glucosides. Because of the semi-aquatic nature of this plant and its extensive contamination with endogenous organisms, the initiation of shoot and callus cultures could only be achieved after (a) using a special surface sterilization procedure, (b) production of new shoots from initial explants, and (c) selective elimination of organogenic structures during several subcultures. HPLC analysis of the cultured tissues established the presence of a number of flavonoids characteristic of the intact plant, though in lower and variable concentrations. However, shoot and callus cultures exhibited flavonoid profiles similar to those of the intact leaves and roots, respectively. PMID- 24241551 TI - Development of somatic embryos from cell suspension cultures of Norway spruce (Picea abies Karst.). AB - Cell suspension cultures were established from embryonal-suspensor masses derived from mature seeds. Transfer of cell masses on to a medium containing abscisic acid stimulated development of already established individual embryos. Somatic embryos developed shoots when supported by cheese cloth in liquid medium in Petri dishes. The percentage of well-developed roots remained low even though all embryos had root meristems. We have recovered an average of 25 plantlets from an initial PCV of ca 1 g fresh wt per 10 ml. PMID- 24241552 TI - Plant regeneration from cell suspension cultures of Vigna aconitifolia. AB - Plant regeneration has been achieved routinely from established cell suspension culture lines of Vigna aconitifolia (moth bean), a highly drought tolerant grain legume. The cultures originated from three-week-old leaf callus. Several media including MS, B5, AA, SL, PCM, SH and L-6 were tested for their effects on cell growth. Maximum growth was observed in L-6 medium containing 44.5 MUM 2,4-D. After 6 to 8 weeks the suspensions were filtered through 500, 250, 125 and 60 MUm sieves, respectively, for four to five subcultures. An embryogenic cell line (VA 686) was obtained from the cell fraction collected below 250 MUm. The VA-686 cell line is being maintained on L-6 medium with 4.5 MUM 2,4-D and 2.3 MUM Zeatin. Somatic embryogenesis was induced by transferring the cells to L-6 medium with 4.6 MUM zeatin in which green cell clusters were produced. The somatic embryos developed from most of the cell clusters when plated on L-6 agar medium with 2.3 MUM BA.Plantlets were obtained from the embryos on L-6 medium with 10.0 MUM IBA. The regenerated plants were grown to maturity in the greenhouse. PMID- 24241553 TI - Production of aposporous gametophytes from Drymoglossum piloselloides (L.) Presl. frond strips. AB - Strips of Drymoglossum piloselloides fronds in a modified Murashige and Skoog medium in 1% agar produced aposporous gametophytes in about 2 months. Young fronds showed a greater ability to develop aposporous gametophytes than older fronds. The addition of kinetin to the medium improved the ability of older fronds while the presence of 1-naphthaleneacetic acid enhanced the effect of kinetin. PMID- 24241554 TI - Somatic embryogenesis and plant regeneration in two-year old cultures of Zea diploperennis. AB - Immature embryos and immature leaf tissues were used to establish embryogenic cultures of Zea diploperennis. Callus was induced on media containing MS salts and vitamins, sucrose (2% for leaves, 6% for embryos), 5% coconut milk and 1-6 mg/l 2, 4-D. Embryogenic callus was maintained by subculturing on media containing MS salts and vitamins, 2% sucrose, 500 mg/l casein hydrolysate and 1 mg/l 2,4-D. Regeneration occurred when the 2,4-D level was reduced to 0.25 mg/l. Kinetin added at 0.25 mg/l further stimulated regeneration. Root tip squashes on 10 plants regenerated after 2 years in culture indicated a normal 2n=20 chromosome number. PMID- 24241555 TI - Somatic embryogenesis from immature embryos of redbud (Cercis canadensis). AB - Somatic embryos developed directly from 96 and 110 day post-anthesis Cercis canadensis L. (redbud) zygotic embryos from one of two trees sampled that were explanted onto modified Schenk and Hildebrandt medium amended with either 1, 2, 3 or 5 mg/1 2,4-D in combination with either 7.6 or 12. 6 mM ammonium ion. Although somatic embryogenesis was expressed on most media, the number of explants that produced somatic embryos and the mean number of embryos formed per explant were greatest on media that contained either 2 or 3 mg/1 2,4-D; 12.6 mM ammonium ion inhibited embryogenesis from 96 day post-anthesis explants. Zygotic embryos explanted 117 days after anthesis produced only callus and roots. Somatic embryos that were bottle-shaped or had distinct cotyledons organized roots on germination media, but only one embryo formed a shoot. No additional development occurred. Histological examination of somatic embryos showed that shoot apical meristems were poorly developed. PMID- 24241556 TI - Erratum. PMID- 24241557 TI - A historical study of mineral elements in forest plants from South Norway. AB - Herbarium plants were used as a material to study possible long-term changes in mineral elements of forest plants. Plants from South Norway collected in the period 1870 to 1930 were compared to plants collected in 1982. Relative to mineral contents in plants from 1870 to 1930, the 1982 material showed elevated levels of Zn, Cd, Rb, K, Mn and Ti and decreased levels of Sr, B, Ca and Mo in some of the plant species analysed. Most of these differences may be explained by changes in the environmental conditions, due to differences in chemical composition of precipitation, accelerated soil acidification and subsequent increasing mineral weathering. Consequently analysis of herbarium plants seems to provide valuable information about preindustrial levels of mineral elements and seems to detect changes in mineral elements brought about by recent anthropogenic activity. PMID- 24241558 TI - The pattern of metal deposition to a woodland ecosystem as revealed by bryophyte analysis. AB - The concentrations and enrichment factor data for 7 metals has been investigated in samples of Hypnum cupressiforme obtained from various parts of a woodland located to the south east of London and immediately adjacent to the M 25 motorway. Despite the rural location of the woodland, metal level and enrichment factor data suggest a moderate degree of contamination. Application of analysis of variance to the data indicates individual metal levels at woodland edges are significantly different from adjacent internal sites, suggesting enhanced deposition at these edges. The fact that this significance pattern is not repeated at all edges indicates a directional influence on levels. Correlation coefficient data indicates metal/metal associations and allows some speculation about the major pathways by which metals are atmospherically transported to and deposited in the woodland. PMID- 24241559 TI - The Asiatic clam, Corbicula spp., as a biological monitor in freshwater environments. AB - Asiatic clams, Corbicula spp., are filter-feeding freshwater bivalves that are widely distributed, abundant, and fast growing with a lifespan of 1-3 yrs. A review of the existing literature demonstrates that Asiatic clams can concentrate organic pollutants from both water and sediment and heavy metals from water. In conjunction with these traits, they exhibit a high tolerance for the effects resulting from exposure to toxic substances. While an organism must possess these traits to serve as an effective biological monitor, they have also permitted the Asiatic clam to rapidly colonize natural and industrial environments resulting in purported ecological disturbances and severe economic repurcussions, respectively. Its invasive biofouling attributes therefore restrict the use of Asiatic clams for biomonitoring purposes from Corbicula-free drainage systems. PMID- 24241560 TI - Migration of pollutants in groundwater. IV. Modeling of the pumping of contaminants from fractured bedrock. AB - The removal of soluble contaminants from fractured porous bedrock by means of a recovery well is modeled by means of a lumped parameter approach. The diffusion of contaminant from immobile liquid within the pores of the fractured rock into the mobile liquid in the interstices is handled by means of a time constant the estimation of which is described. PMID- 24241561 TI - Impact of distillery effluent application to land on soil microflora. AB - A pot culture experiment was conducted to evaluate the effect of different treatments of distillery wastewater, i.e. raw, treated, diluted and raw distillery wastewater mixed with domestic waste stabilization pond effluent (1:1) on populations of bacteria, fungi, actinomycetes and nitrogen fixing bacteria. The results indicated that raw wastewater decreased the population of bacteria, fungi and actinomycetes. The growth rates of Rhizobium and Azotobacter were also reduced after raw wastewater application. The toxic effect of raw wastewater was minimized when it was mixed with stabilization pond effluent (1:1), this was demonstrated by an increase in the populations of all the microorganisms studied. When a groundnut plant was irrigated with raw distillery wastewater, no fruits were produced and there was also less nodulation. This study indicates that raw distillery wastewater is very toxic to the soil microorganisms which are important in the soil ecosystem. PMID- 24241562 TI - Morphology and ultrastructure of 11 barley shrunken endosperm mutants. AB - Eleven Na-azide induced barley shrunken endosperm mutants expressing xenia (sex) were characterized genetically and histologically. All mutants have reduced kernel size with kernel weights ranging from 11 to 57% of the wild type. With one exception, the mutant phenotypes are ascribable to single recessive mutant alleles, giving rise to a ratio of 3?1 of normal and shrunken kernels on heterozygous plants. One mutant (B10), also monofactorially inherited, shows a gene dosage dependent pattern of expression in the endosperm. Among the 8 mutants tested for allelism, no allelic mutant genes were discovered. By means of translocation mapping, the mutant gene of B10 was localized to the short arm of chromosome 7, and that of B9 to the short arm of chromosome 1. Based on microscopy studies, the mutant kernel phenotypes fall into three classes, viz. mutants with both endosperm and embryo affected and with a non-viable embryo, mutants with both endosperm and embryo affected and with a viable embryo giving rise to plants with a clearly mutant phenotype, and finally mutants with only the endosperm affected and with a normal embryo giving rise to plants with normal phenotype. The mutant collection covers mutations in genes participating in all of the developmental phases of the endosperm, i.e. the passage from syncytial to the cellular endosperm, total lack of aleurone cell formation and disturbance in the pattern of aleurone cell formation. In the starchy endosperm, varying degrees of cell differentiation occur, ranging from slight deviations from wild type to complete loss of starchy endosperm traits. In the embryo, blocks in the major developmental phases are represented in the mutant collection, including arrest at the proembryo stage, continued cell divisions but no differentiation, and embryos deviating only slightly from the wild type. PMID- 24241563 TI - Enzyme diversity in pearl millet (Pennisetum glaucum) : 1. West Africa. AB - Polymorphism in twelve genes coding for eight enzymes in pearl millet (Pennisetum glaucum (L.) R. Br.): alcohol dehydrogenases (ADH), catalases (CAT), beta esterases (EST), glutamate oxaloacetate transaminases (GOT), malate dehydrogenases (MDH), 6-Phosphogluconate dehydrogenases (PGD), phosphoglucoisomerases (PGI) and phosphoglucomutases (PGM), was observed by electrophoresis on 74 cultivated samples and 8 wild samples from West Africa. Six genes: Est A, Adh A, Pgm A, Cat A, Pgi A, Pgd A contain 95% of the total variation. Principal component analyses and discriminant analyses of the 82 samples described by 46 allelic frequencies showed an almost complete separation into 3 groups: wilds, early maturing cultivars and late maturing cultivars. The early group has the highest enzyme diversity, with cultivated millets from Niger showing the most diversity. The high diversity of the early group and its extensive divergence from West-African wild millets suggest, firstly, the existence, elsewhere in Africa of other enzymatically different sources of wild millet, and secondly, the occurrence, prehistorically, of several different domestications. The late group of cultivars has the lowest variability and a relatively low coefficient of differentiation. This relatively homogeneous enzyme structure does not seem to be associated to ecology. A hypothesis is advanced suggesting that West African late-cultivars were derived from a common cultivated early complex. This complex must have been distributed across the Sudanian zone and must have been later sumitted to modifications by limited gene flow with local early maturing cultivars. PMID- 24241564 TI - Is the polymorphism of protein amounts related to phenotypic variability? A comparison of two-dimensional electrophoresis data with morphological traits in maize. AB - The hypothesis that the quantitative variations in gene product levels could be a more important basis for morphological and adaptative change than the classical qualitative variability revealed by electrophoretic techniques was studied by comparing five maize lines from three sets of variables: (i) qualitative variations of proteins (presence/absence) revealed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), at a physiological seedling stage; (ii) quantitative variations in proteins (spots more or less intense) revealed by 2D PAGE, at the same physiological stage; (iii) general combining abilities of fourteen heritable, morphological or agronomical characters measured at various juvenile and adult stages. Distances between lines were defined, based on qualitative and quantitative variations of proteins. These distances do not appear to be correlated and do not give the same patterns of divergence between lines, as shown by principal coordinate analyses. Mahalanobis distances computed from the general combining abilities of the morphological characters are significantly correlated (r=0.75) to quantitative but not to qualitative distances. The comparison of the first planes of the principal coordinate analyses performed on the three kinds of distances clearly confirms this finding. Our results are discussed in connection with the possible genetic meaning of the two molecular distances and with the hypothesis that regulatory processes are primarily implicated in morphological variation. PMID- 24241565 TI - Inheritance of annual habit in celery: cosegregation with isozyme and anthocyanin markers. AB - Vernalization response was determined in an annual and two biennial celery strains, Apium graveolens L. and their F2 hybrids. Although the annual strain did not require vernalization to bolt, plants exposed to 10 degrees C for 7 days bolted 2 weeks earlier than non-treated plants. Inheritance studies based on F2 and backcross segregations demonstrate that annual habit in celery is partially dominant over biennial and determined by a single gene designated Hb. Cosegregation studies of this trait with nine isozyme loci and a gene determining petiole anthocyanin pigmentation disclosed the following linkage relationships: Adh-1-Sdh-1-Mdh-1, and Got-1-Mdh-2-Hb-A. The recombination frequency observed for Hb and Mdh-2 was too large to use the latter as a useful marker for annual habit. PMID- 24241566 TI - Genetic variability for heat shock proteins in common wheat. AB - The response of the common wheat line 'Chinese Spring' to heat shocks of different time lengths was studied by the two-dimensional (2D) electrophoresis of denatured proteins. After a heat shock of 5 h, 33 heat shock proteins (HSPs) accumulated in an amount sufficient to be revealed by silver stain. Two other wheat lines ('Moisson' and 'Selkirk') were then submitted to a heat shock of 5 h, and the responses of the 3 lines were compared: of a total of 35 HSPs, 13 (37.1%) were quantitatively or qualitatively variable. This variability concerns low molecular-weight and high-molecular-weight HSPs. The three genotypes showed thermal tolerance but 'Chinese Spring's' response to heat treatments was slightly different from those of the other two lines The possibility of a relationship between HSP patterns and thermal sensitivity is discussed. PMID- 24241567 TI - A guide to the homoeology of chromosomes within the Triticeae. AB - A method of assessing chromosome homoeologies within the genomes of the Triticeae which does not require the ultimate test of substitution of the chromosomes into wheat is presented. This takes the form of a table listing key characters that are associated with specific homoeologous groups. These characters include marker genes, chromosome morphology, and plant morphologies of wheat-alien chromosome addition and wheat tetrasomic lines. PMID- 24241568 TI - Parental genome expression in synthetic wheats (Triticum turgidum sp. * T. tauschii sp.) revealed by two-dimensional electrophoresis of seedling proteins. AB - Two-dimensional gel electrophoresis was conducted on etiolated seedling proteins from two distinct amphiploids (ABD1, ABD2) and their parental lines (AB1, D1 and AB2, D2), AB1 and AB2 being used as female. On the amphiploid patterns were found all the parental spots except 8 D spots of which 3 are cytoplasmically encoded. One exceptional polypeptide observed in ABD1 was present neither in AB1 nor D1. The patterns fromt the amphiploids very closely resemble the co-electrophoresis done with 1/3 D protein extract and 2/3 AB protein extract. Thus it is very likely that for most gene products revealed the genomes act independently of each other. PMID- 24241569 TI - Differentiation of rice varieties by electrophoresis of embryo protein. AB - Variations in the embryo proteins separated by SDS-PAGE have been observed in 43 cultivated varieties of Oryza sativa L. Cluster and discriminant analysis applied to both protein components and morphological characters indicate that knowledge of the differences in embryo proteins can improve our understanding of genetic affinity and make it easier to differentiate between varieties of similar genetic backgrounds. PMID- 24241570 TI - Cytogenetics of Lolium perenne : 4. Colchicine induced variation in diploids. AB - A number of diploid inbred lines of Lolium perenne were treated with colchicine at the early seedling stage to induce chromosome doubling. In each inbred line the colchicine-treated undoubled diploids were kept as controls, as well as the normal untreated diploids. Comparisons of vegetative growth and development, involving the three treatments within each line, revealed that colchicine treatment of seedlings has long-lasting effects upon plant growth and development independent of chromosome doubling, and that for certain characteristics the effects of chromosome doubling are confounded with other effects of the treatment used to produce tetraploids. This colchicine induced variation in the diploids is transmitted through the seed generations in at least one of the inbred lines. The variation appears to be non-random and also shows a strong genotypic component. In so far as the effects of chromosome doubling could be determined, they showed the usual gigas response but were again strongly influenced by genotype. PMID- 24241571 TI - Cytogenetic studies of the F1 hybrids of Capsicum annuum with C. chinense and C. baccatum. AB - Partially sterile interspecific hybrids were obtained between C. annuum var. 'cerasiformis' and C. chinense var. 'mishme' (H1), and C. annuum var. 'cerasiformis' and C. baccatum var. 'pendulum' (H2). Morphologically the F1 hybrids were intermediate between the corresponding parents. Meiosis was irregular in the two F1 hybrids. Cytological analysis of the two F1 hybrids revealed that the genome of C. annuum differs from C. chinense by two translocations and some minor structural alterations and from C. baccatum by two translocations, a single inversion and some minor structural alterations. Isolation barriers such as hybrid inviability, weakness and hybrid breakdown in the H1 hybrid and, inaddition, desynapsis in the H2, were operative in these taxa. The differences between the present findings and those reported earlier on the two F1hybrids were attributed to differences in the genetic architecture of the taxa employed in hybridization. PMID- 24241572 TI - Sister chromatid exchange in vivo, chromosomal characterization and NORs activity of leukemia cells during 5FU-treatments. AB - A transplantable mouse leukemia model, the leukemia cell of which has a marker chromosome and the XX genome type which differ obviously from their male host cells provides a possibility to precisely identify the leukemia cells among their male host cells cytogenetically. A sister chromatid exchange (SCE) plus chromosomal C-banding technique that we report here is very useful. The SCE frequencies in vivo of both leukemia cells and host cells were twice as high as the normal mouse cells. The higher SCE frequencies of the host cells in the leukemia mice may be due to some toxicities from the leukemia cells or some biological large molecule exchanges between the leukemia cells and the host cells. There was no significant difference in SCE frequencies between cells from the spleen and from the bone marrow of the leukemia mice. The percentages of leukemia cells in both spleen and bone marrow were more than 90% when the mice had been injected with the leukemia cells for five days. The host cells in the leukemia mice did not become leukemia cells. The 5FU-treated leukemia mice survived very well for more than twenty-three days. After the 5FU-treatments, most of the leukemia cells died, subsequently, SCE frequencies decreased to a normal level. Both the number of Ag-NORs per cell and the number of chromosomes bearing Ag-NORs per cell in the leukemia mice decreased to 60% and 40%, respectively, of the level found in normal mouse cells. PMID- 24241574 TI - Identification and chromosomal locations of aconitase gene loci in Triticeae species. AB - Two systems of monomeric aconitase (ACO) isozymes, designated ACO-1 and ACO-2, were identified in Triticum aestivum and in five diploid Triticeae species. The gene loci Aco-A1, Aco-B1, and Aco-D1 were located in T. aestivum cv. 'Chinese Spring' chromosome arms 6Aq, 6Bq, and 6Dq, respectively, and the gene loci Aco A2, Aco-B2, and Aco-D2 in 5 Aq, 5 Bq, and 5Dq, respectively. Aco-1 gene loci were also identified in 6Ebeta of Elytrigia elongata, 6HL of Hordeum vulgare cv. 'Betzes', 6RL of Secale cereale 'PI 252003', 6S(1) of T. longissimum, and CSU-31 of T. umbellulatum. Other Aco-2 gene loci were identified in 5RL of S. cereale cv. 'King II' and 4EL of E. elongata. Conservation of synteny relationships is indicated among the species studied for the genes identified, with the exception of Aco-E2; the presence of this gene in 4EL suggests that E. elongata differs from 'Chinese Spring' and 'King II' by a translocation involving 4E and 5E. PMID- 24241573 TI - Phenotypic and genetic variations in crown-gall tumour cells of tobacco. AB - Phenotypic and genetic variations of tumour cells were analysed both quantitatively and qualitatively in clones and subclones of a crown-gall strain. Thus, growth rates, grafting tests, octopine synthesis, estimations of the T-DNA contents, modifications in the numbers, and structures of chromosomes were examined. Phenotypic variations are closely associated with genetic changes, including variation in chromosome number (which is shown to be non-specific to the tumoral state) and, above all, variation in the copy-number of T-DNA sequences per cell, and structural rearrangements of chromosomes. Such rearrangements are characterized by specific marker chromosomes in the tumour cells and they correlate with the degree of oncogenicity of the cells. PMID- 24241575 TI - Probabilities of negative estimates of genetic variances. AB - The probability of negative analysis of variance estimates of genetic variance components due to sampling error (Ps) was investigated. The objectives were to evaluate the magnitude of Ps, to compare Ps for estimates of sigma A (2) and sigma D (2) , and to compare Ps for genetic variance component estimates from the nested and factorial mating designs. Ps was defined in terms of ratios of mean squares and the F distribution was used to calculate probabilities of the negative estimates. The results indicated that Ps is often greater than 0.20 for sigma D (2) . It is generally lower for sigma A (2) than for sigma D (2) , and lower for the factorial mating design than the nested mating design. PMID- 24241576 TI - A new selection criterion for yield in wheat. AB - The mortality of young tillers to an extent of 36.5% under optimum cultural conditions was recorded in a field experiment. Attention is drawn to the necessity of minimising this loss and to diverting it towards productive tillers by applying selection pressure. Future yield advances may be achieved by selecting genotypes which tiller moderately in the vegetative phase, most of which survive to produce grains. The character association of each variety under consideration was studied for the suitability towards this objective. A modified selection procedure is suggested which may be advantageously applied to achieve this objective. The proposed new methodology may also be effectively applied to such other cereal crops as barley, triticale and oats. PMID- 24241577 TI - Correlation studies on yield and fibre traits in upland cotton (Gossypium hirsutum L.). AB - Two diverse parents of upland cotton namely J.34 and I.C. 1926 were crossed. A comparison between biparental intermated progenies and F3 families indicated alteration of correlation coefficient between yield and halo length. The significant negative correlation in F3 population between these two attributes changed to a positive but non significant one in biparental intermated progenies. A change in correlation coefficients was expected due to breakage of linkage upon intermating. An increase in the correlation coefficients could also be expected when linkages are predominantly in the repulsion phase. It is suggested that intermating in early generations coupled with selection of desirable segregants may prove a useful method for improving yield and quality simultaneously. The diallel selective mating system may also supplement intermating to improve yield and quality in cotton. PMID- 24241578 TI - Genetic analysis of anther culture response in maize. AB - Response frequencies in maize (Zea mays L.) anthers cultured in vitro were examined in a diallel set of crosses among four commercial inbred lines. Significant differences among the genotypes were observed, with the crosses H99xFR16 and Pa91xFR16 displaying the highest responses. General (GCA) and specific (SCA) combining ability mean squares were calculated and determined to be highly significant. GCA effects among the parental lines were highest for FR16 and lowest for LH38. Nongenotypic, plant-toplant differences were also found to make a significant contribution to the overall variation observed. The results from this study indicate that parents which give rise to highly responsive hybrids can be identified and that genetic improvement is possible through selection. PMID- 24241579 TI - A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality. AB - For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia. PMID- 24241580 TI - Contrast enhanced cardiac CT reveals coronary artery disease in 45% of asymptomatic allo-SCT long-term survivors. PMID- 24241581 TI - Long term outcomes after lateral anal sphincterotomy for anal fissure: a retrospective cohort study. AB - PURPOSE: Lateral anal sphincterotomy is the gold standard of surgical treatment for anal fissure. Patients undergoing this procedure are warned about the risk of incontinence; however, there are few reports on long-term outcomes. We conducted this study to investigate long-term outcomes after lateral anal sphincterotomy, focusing specifically on postoperative incontinence. METHODS: Patients who underwent lateral anal sphincterotomy at a university teaching hospital between 1998 and 2004 were sent questionnaires to allow us to assess their continence according to the Cleveland Continence Score. RESULTS: The response rate was 58 % and the responders comprised 25 men and 13 women, with a median age of 49 years (range 16-82 years). The success rate for fissure healing following surgery was 92 %, being significantly more likely in patients with textbook symptoms (p = 0.016) and those with chronic disease (p = 0.006). The overall complication rate was 13.2 %. Long-term objective and symptomatic incontinence were reported by two (5.6 %) patients, one of whom required a colostomy. CONCLUSION: Success rates after lateral anal sphincterotomy were satisfactory, but careful patient selection based on symptoms and disease chronicity may improve results further. Patients with predisposing risk factors for the development of incontinence, particularly multiparous women, are arguably better treated with non-surgical options. PMID- 24241582 TI - Attending to warning signs of primary immunodeficiency diseases across the range of clinical practice. AB - PURPOSE: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. METHODS: Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. RESULTS: Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. CONCLUSIONS: This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty. PMID- 24241583 TI - Sporothrix schenckii lymphadentitis in a male with X-linked chronic granulomatous disease. AB - Sporothrix schenckii lymphadenitis was identified in a 33 month old male with X linked chronic granulomatous disease (CGD). S. schenckii is a dimorphic catalase producing fungus found in the soil of temperate and tropical climates. Host defense against S. schenckii relies primarily on innate and cellular responses and gp91(phox-/-) mice are susceptible to disseminated infection. This case represents the first report of susceptibility to sporotrichosis in a patient with CGD. PMID- 24241584 TI - Role of environmental factors and toxic genotypes in the regulation of microcystins-producing cyanobacterial blooms. AB - The aim of this study was to understand: (1) how environmental conditions can contribute to formation of Microcystis-dominated blooms in lowland, dam reservoirs in temperate climate-with the use of quantitative molecular monitoring, and (2) what is the role of toxic Microcystis genotypes in the bloom functioning. Monitoring of the Sulejow Reservoir in 2009 and 2010 in two sites Tresta (TR) and Bronislawow BR), which have different morphometry, showed that physicochemical conditions were always favorable for cyanobacterial bloom formation. In 2009, the average biomass of cyanobacteria reached 13 mg L(-1) (TR) and 8 mg L(-1) (BR), and in the second year, it decreased to approximately 1 mg L(-1) (TR and BR). In turns, the mean number of toxic Microcystis genotypes in the total Microcystis reached 1% in 2009, both in TR and BR, and in 2010, the number increased to 70% in TR and 14 % in BR. Despite significant differences in the biomass of cyanobacteria in 2009 and 2010, the mean microcystins (MCs) concentration and toxicity stayed at a similar level of approximately 1 MUg L( 1). Statistical analysis indicated that water retention time was a factor that provided a significant difference between the two monitoring seasons and was considered a driver of the changes occurring in the Sulejow Reservoir. Hydrologic differences, which occurred between two studied years due to heavy flooding in Poland in 2010, influenced the decrease in number of Microcystis biomass by causing water disturbances and by lowering water temperature. Statistical analysis showed that Microcystis aeruginosa biomass and 16S rRNA gene copy number representing Microcystis genotypes in both years of monitoring could be predicted on the basis of total and dissolved phosphorus concentrations and water temperature. In present study, the number of mcyA gene copies representing toxic Microcystis genotypes could be predicted based on the biomass of M. aeruginosa. Moreover, MCs toxicity and concentration could be predicted on the basic of mcyA gene copy number and M. aeruginosa (biomass, 16S rRNA), respectively. Present findings may indicate that Microcystis can regulate the number of toxic genotypes, and in this way adjust the whole bloom to be able to produce MCs at the level which is necessary for its maintenance in the Sulejow Reservoir under stressful hydrological conditions. PMID- 24241585 TI - Pharmacological profile of astemizole-derived compounds at the histamine H1 and H4 receptor--H1/H4 receptor selectivity. AB - Astemizole, a H1R antagonist shows high affinity to the histamine H1 receptor but only a moderate affinity to the histamine H4 receptor. This study aims to modify the astemizole to keep high affinity to the histamine H1 receptor and to increase affinity to the histamine H4 receptor. Therefore, 13 astemizole-derived compounds and astemizole-JNJ7777120-derived hybrid compounds were synthesized and pharmacologically characterized at the histamine H1 and H4 receptors. The new compounds show affinity to the histamine H1 receptor in the pK i range from 5.3 to 8.8, whereas the affinity of these compounds to the histamine H4 receptor was surprisingly rather low (pK i from 4.4 to 5.6). Three representative compounds were docked into the histamine H1 receptor and molecular dynamic studies were performed to explain the binding mode and the experimental results on a molecular level. Furthermore, taking into account the binding mode of compounds with high affinity to the histamine H4 receptor, a H1/H4-pharmacophore hypothesis was developed. PMID- 24241587 TI - High-speed electro-fusion and electro-transfection of plant protoplasts by a continuous flow electro-manipulator. AB - A continuous flow electro-manipulator available both for mass production of fused and of transfected plant protoplasts was devised using a flow chamber with gold coated glass panel electrodes. Up to 100 ml of protoplasts suspension were treated within 20 min at the rate of approximately 1*10(6) protoplasts / min. The yield of diheterokaryons between tobacco mesophyll and carrot root protoplasts reached approximately 10 % of total protoplasts by flow electro-fusion. More than 95 % of tobacco and cowpea mesophyll protoplasts became infected with tobacco mosaic virus RNA by flow electro-transfection. PMID- 24241588 TI - Dominant expression of a gene amplification-related herbicide resistance in medicago cell hybrids. AB - Protoplasts from phosphinotricin resistant M. sativa and M. varia cell lines carrying an amplified glutamine synthethase gene were fused with leaf protoplasts of kanamycin resistant M. varia transformants. The dominant nature of both PPT and kanamycin resistant traits was shown by the double resistant phenotype of the intra- and interspecific cell hybrids obtained. The presence of amplified GS gene in the hybrid genomes and the expression of chimeric neomycin phosphotransferase II gene was detected. The highly embryogenic character of the M. varia parent was not expressed after cell fusion. All hybrid cell lines with the double resistant phenotype showed non-morphogenic growth similarly to the PPT resistant parent. The possible role of GS gene amplification and other factors in the dominant behaviour of unorganized cell growth in alfalfa somatic hybrids is discussed. PMID- 24241586 TI - Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine. AB - One of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a "bridge" for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration. PMID- 24241589 TI - Growth of cucumber cells in media with lactose or milk whey as carbon source. AB - Lactose utilisation by cucumber cell suspension cultures starts only after a long lag phase and is accompanied by an increase of an extracellular lactosespecific beta-galactosidase activity. Supplementing the lactose medium with sucrose shortens the lag phase.Milk whey permeate seems to contain a factor(s) which inhibits lactose utilisation. After supplementing the medium with sucrose or its hydrolysis products, growth and substrate utilisation is as efficient as in Murashige and Skoog medium. Galactose also induces growth, but growth and substrate utilisation are slower. In whey medium, supplemented with sucrose, the extracellular beta-galactosidase activity again accompanies growth induction. PMID- 24241590 TI - Influence of benzyladenine on condensed tannin formation and callus growth in cultures from sainfoin (Onobrychis viccifolia Scop.) cotyledons. AB - Cotyledons from aseptically grown seedlings of sainfoin (Onobrychis viciifolia Scop.) were used as explant material to grow callus tissue for periods of 21 and 31 days. The formation of cells containing condensed tannins was induced by adding a range of BAP concentrations to an mB5 culture medium containing 2,4-D. After 21 days the fresh weight of calli treated with BAP was much greater than the control and appeared highest at the 0.6 mg/L level. Fresh weight was reduced at high BAP levels (2 to 8 mg/L) but still remained well above the control. The formation of tannin-filled cells was genotype-specific but occurred in all treatments with BAP. After 21 days in culture, fresh weight and tannin formation increased with the BAP level at the lower BAP concentrations. After 31 days, the growth rate slowed in the control and the lower BAP concentration, but continued at a high rate in the remaining treatments; the number of tannin-filled cells appeared to decline. The results show that in sainfoin callus culture, BAP induces the formation of condensed tannin, a secondary metabolite, and concomitantly produces a high growth rate. PMID- 24241591 TI - Resistance to freezing in liquid nitrogen of carnation (Dianthus caryophyllus L. var Eolo) apical and axillary shoot tips excised from different aged in vitro plantlets. AB - The ability of shoot tips from carnation (Dianthus caryophyllus L., var. Eolo) cultured in vitro to develop resistance to freezing in liquid nitrogen depends on the physiological state of the cell material and the pretreatment conditions. Regrowth rates close to 100% have been obtained with apical shoot tips isolated from 2 month-old stems, precultured on medium supplemented with sucrose (0.75M) and treated with dimethylsulfoxide (5% or more). Resistance of axillary shoot tips decreased progressively as a funtion of their distance from the apical shoot tip. During the development of the stem from axillary buds (obtained by cutting), progressive increases in the regrowth rate of frozen apices were noted, from 30% before cutting (axillary buds) to 98% after 3 weeks of culture. PMID- 24241592 TI - Plantlet regeneration from mature zygotic embryos of eastern white pine (Pinus strobus L.). AB - Plants were regenerated from whole embryo explants obtained from eastern white pine (Pinus strobus L.) seeds. Embryos were surgically removed and axenically cultured to induce buds in vitro on a modified Murashige and Skoog medium containing various concentrations of 6-benzylaminopurine. Embryos remained on bud induction medium for 21 days and then were transferred to the same basal medium without 6-benzylaminopurine to promote bud development and subsequent shoot elongation. The medium containing 10 MUM 6-benzylaminopurine induced the greatest number of shoots per embryo. Rooting was achieved by direct transfer of the shoots to a non-sterile artificial soil mixture followed by multiple treatments with 15 nM 1-naphthaleneacetic acid. Regenerated seedlings are currently growing under greenhouse conditions. PMID- 24241593 TI - Modulation of soluble auxin-binding proteins in soybean cell suspensions. AB - Rapidly growing cell suspensions of soybean were analyzed for the presence of cytoplasmic high-affinity binding sites for auxin. Cytosol preparations were studied in lag, log and early stationary phase of the growth cycle. Two binding sites were detected, which show some similarities with binding sites previously reported from etiolated pea epicotyls. While the number of both sites declined in the cytoplasm during the growth cycle, the number of one of the two sites increased at the onset of rapid cell divisions. In parallel, both sites exhibited an increase in binding affinity during the growth cycle. The data will be discussed in relation to other reports on soluble auxin binding as well as to possible physiological functions. PMID- 24241594 TI - N5-Formyltetrahydrofolate counteracts methotrexate toxicity in tobacco cell culture. AB - N5-Formyltetrahydrofolate (leucovorin) counteracted methotrexate toxicity in suspension cultures of Nicotiana tabacum var. Xanthi. Methotrexate at 50 nM inhibited growth of the tobacco cell cultures by 87%. Leucovorin at 200 uM reduced growth inhibition in methotrexate-treated cultures to 37%, but only if exogenous adenine and thymidine were simultaneously provided. In the absence of leucovorin, neither adenine plus thymidine, nor adenine plus thymidine plus methionine gave appreciable relief from methotrexate toxicity. Uptake of radioactive methotrexate at 50 nM was linear for at least 7 h. Uptake of methotrexate appeared to be saturable, with a Km of 50 uM and a Vmax of 1 nmol h( 1) g(-1) fresh weight. Leucovorin showed competitive inhibition of methotrexate uptake, having a Ki of 400 uM. PMID- 24241595 TI - Permeabilization of cultivated plant cells by electroporation for release of intracellularly stored secondary products. AB - Plant cell suspension cultures producing secondary metabolites have been permeabilized for product release by electroporation. The two cell cultures studied, i.e. Thalictrum rugosum and Chenopodium rubrum, require about 5 and 10 kV cm(-1), respectively, for complete permeabilization (release of all the intracellularly stored product). The number of electrical pulses and capacitance used had a relatively limited effect on product release while the viability of the cells was strongly influenced by the latter. Conditions for complete product release resulted in total loss of viability of the cells after treatment. The release of product from immobilized cells was also achieved by electroporation. Cells entrapped in alginate required less voltage for permeabilization than free or agarose entrapped cells. PMID- 24241596 TI - Inhibition of growth and xylogenesis and promotion of vacuolation in prunus callus by the flavanone prunin. AB - Callus tissue of Prunus avium L. responded to supplied prunin (naringen in 7 glucoside) showing vaculoation and storage of oligomeric proanthocyanidins. In addition, prunin caused restricted callus initiation and/or less callus growth. When prunin was omitted from the medium numerous tracheids and more peroxidases were formed in the callus. PMID- 24241597 TI - In vitro culture of cell aggregates of rye (Secale cereale L.) at low densities. AB - The growth of cell aggregates from a rye suspension culture was tested at low density in three culture systems. Mass seeding was the most supportive system, followed by agarose droplets. Microdroplet culture using Cuprak dishes was the least effective system. Growth was stimulated by the presence of a feeder layer of suspension cells but only if the feeder contact with the nursed cells was via a liquid and not a gaseous phase. Plating efficiences were enhanced by the feeder effect, whereas the subsequent growth rates were less affected. The techniques described should prove useful in programs aimed at the in vitro genetic manipulation of rye or other cereals. PMID- 24241598 TI - Cell cultures of the wild sunflower Helianthus maximiliani schrader: growth and secondary metabolite synthesis. AB - Callus cultures derived from leaves, stem, sepals and ray flowers and cell suspension cultures of Helianthus maximiliani Schrader were established and analysed for their phytochemicals. Dark-grown cultures were found to synthesize small amounts of non-toxic, polycyclic diterpenoids when grown on modified MS medium, while beta-sitosterol and palmitic acid were found in dark- and light grown cultures. Red light irradiation did not enhance terpenoid production compared to dark- and light-grown cells. PMID- 24241599 TI - Callus formation from leaf mesophyll protoplasts of Malus Xdomestica Borkh. cv. Greensleeves. AB - Large yields (1.85 * 10(7)/g.f.wt.) of viable protoplasts were obtained from leaves of axenic shoot cultures of Malus Xdomestica Borkh. cv. 'Greensleeves'. Protoplasts cultured in liquid or agarose semi-solidified KM8P medium underwent cell wall regeneration and colony formation.Protoplast-derived cell colonies developed to callus on semi-solid KM8 medium. This is the first report of callus formation from mesophyll protoplasts of apple. PMID- 24241600 TI - Clonal propagation of Picrorhiza kurroa royle ex benth. by shoot tip culture. AB - A procedure has been developed for the clonal propagation of Picrorhiza kurroa Royle ex Benth. through shoot tip culture. Murashige and Skoog's medium (1962) supplemented with kinetin (3.0 to 5.0 mg/l) supported rapid proliferation of multiple shoots from the explants. Addition of indole-3-acetic acid (1.0 mg/l) to the kinetin containing medium showed marked improvement in the growth of regenerated shoots. However, presence of IAA in the medium did not alter the frequency of shoot multiplication. Rooting was readily achieved upon transferring shoots onto MS medium containing ?-naphthaleneacetic acid (1.0 mg/l). Plantlets were successfully transferred to soil. PMID- 24241601 TI - Somaclonal variation in the berberine-producing capability of a culture strain of Thalictrum minus. AB - Variation in the productivity of berberine between clonal cell lines derived from a culture strain of Thalictrum minus. var. hypoleucum was investigated during the period of successive transfer generations. There was a correlation between berberine productivity and growth in these clonal cultures. Although no significant difference was found in the secretory function as well as the qualitative pattern of alkaloids, there was wide variation in the yield of berberine among the clones. Some of the cell lines have shown a high stability throughout the successive subculturing, whereas the other lines tended to either decrease or increase the productivity continually before they have become more or less stable at low or high levels. After eight months of subculturing, one of the high-producing cell lines yielded 0.76 g of berberine per liter in 14 days of culture strain. In view of variations observed in both primary and secondary clones, the possible cause of the quantitative variation in berberine production in Thalictrum cultures is discussed. PMID- 24241602 TI - Plant regeneration from protoplasts of Capsicum annuum. AB - Leaf protoplasts were isolated from axenic shoot cultures of four varieties of Capsicum annuum (Americano, Dulce Italiano Florida Gynat and Nigrum) and a wild species C. chinense. Protoplasts of both species, cultured in KM8P medium and using agarose bead culture, entered division with the exception of the variety Nigrum. Cell colonies formed callus in agar-solified MS medium supplemented with zeatin and for C. annuum v. Dulce Italiano shoots were regenerated when protoplast-derived calli were transferred to MS medium with 6-BAP. Excised shoots were rooted on MS medium which lacked phytohormones. PMID- 24241603 TI - Evidence for involvement of ketoglutarate in the biosynthesis of Canthin-6-one from cell cultures of Ailanthus altissima. AB - (13)C enrichments at C-3, C-4, C-5 and C-6 of canthin-6-one from cell cultures of Ailanthus altissima supplemented with [1-(13)C], [2-(13)C] and [1,2-(13)C] acetate, give evidence of the involvement of ketoglutarate as an intact precursor in the biosynthetic pathway. PMID- 24241604 TI - Analyzing the effects of exogeneous polyamines and growth regulators on plating efficiency of sweet potato protoplasts using a central composite test design. AB - The effects of exogenous polyamines and growth regulators on plating efficiency of greenhouse-grown sweet potato (Ipomoea batatas Lam.) petiole protoplasts after six days were analyzed using a central composite test design. The medium components screened were 1-naphthaleneacetic acid (NAA), 6-benzylaminopurine (BAP), putrescine (PUT), spermidine (SPD), and spermine (SPM), each at five concentrations. Stepwise multiple regression analysis revealed significant interaction of NAA with BAP, PUT, and SPD as reflected in plating efficiencies. The interactions of NAA with BAP, and with SPD, were positive. The interaction of NAA and PUT appeared complex. A slight negative interaction was detected between PUT and SPM. These results indicated that plating efficiency of sweet potato protoplasts is highly sensitive to the concentrations of the medium components tested and it should be possible to further optimize the plating medium. Among the media formulations tested, the highest plating efficiency (10.8% after 6 days) was observed with NAA at 4.5 uM, BAP at 1.5 uM, PUT at 35.0 uM, SPD at 5.0 uM, and SPM at 2.5 uM. PMID- 24241605 TI - Erratum. PMID- 24241606 TI - Efficacy of a 12-month, monitored home exercise programme compared with normal care commencing 2 months after total knee arthroplasty: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy of a delayed home exercise programme compared with normal care after primary total knee arthroplasty. DESIGN: Single-blind, prospective, randomized, controlled trial. PARTICIPANTS: A total of 108 participants (61% females, mean age 69 years [standard deviation 8.7]), were randomized to a home-based exercise group (EG, n = 53) or to a control group (CG, n = 55). METHODS: Two months post-operatively, the EG received a home exercise programme, while the CG received no additional guidance. The outcome measurements were: pain and disability, measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); health-related quality of life (HRQoL), measured using the Short Form-36 questionnaire (SF-36); maximal walking speed; isometric knee muscle strength; and the Timed Up and Go (TUG) test. Measurements were made at baseline and at 12 months thereafter. RESULTS: At the 12-month follow-up, maximal walking speed (p < 0.001) and knee flexion strength (p = 0.009) were significantly greater in the EG. Both groups showed similar improvements in all of the WOMAC subscale scores, the SF-36 summary scores and the TUG time. CONCLUSION: Home-based training was not superior to normal care with regard to pain, disability or HRQoL, but resulted in greater improvement in objectively measured physical performance. PMID- 24241607 TI - Cardiovascular disease among breast cancer survivors: the call for a clinical vascular health toolbox. AB - With better detection and treatment, breast cancer is less likely to be the primary cause of death in the majority of breast cancer survivors; mortality due to cardiovascular disease (CVD) is now more common. Given the long latency periods between cancer treatment completion and potential symptomatic CVD, there is a need to detect vascular changes before symptoms appear. This short review provides an overview of non-invasive, widely available, and relatively inexpensive techniques for assessing endothelial function, central and regional arterial stiffness, central blood pressures, and intima-media thickness. These tools exhibit acceptable reliability and validity, and are relatively practical. Clinical assessment recommendations are also provided. There is sufficient evidence to encourage the use of these techniques as a component of routine serial assessments, and to help guide appropriate treatment strategies. PMID- 24241608 TI - Nucleotide pools in suspension-cultured cells of Datura innoxia : I. Changes during growth of the batch culture. AB - The concentrations of 17 nucleotides and three nucleosides have been determined in a batch suspension culture of Datura innoxia using a new procedure for extraction, purification and high-performance liquid chromatography separation of these compounds. The nucleotide pools change appreciably in the different phases of growth. These changes indicate the preparation for and initiation of cell proliferation, and reflect metabolic events during cell division, cell elongation and starvation. The main components of the nucleotide pool are uracil nucleotides, with uridine 5'-diphosphate sugars as the predominant fraction, and the adenine nucleotides. Although their concentrations vary by a factor of more than 6 the ratio of the uracil to adenine nucleotides is kept fairly constant during growth. The energy charge is maintained at a rather high value. The correlation of these events with nutrient uptake and macromolecular synthesis by the batch culture is presented in the following paper. PMID- 24241609 TI - Nucleotide pools in suspension-cultured cells of Datura innoxia : II. Correlation with nutrient uptake and macromolecular synthesis. AB - A general picture of the metabolic events which govern to growth behaviour of a batch culture of suspended dedifferentiated cells of Datura innoxia is obtained by following both the uptake and accumulation of the medium phosphate and sucrose by the cells, and the synthesis of RNA, protein and starch. The results are compared with the changes in the nucleotide pools described in the preceding paper. The sequence of formation and the regulatory dependencies of cellular pools of phosphate, sucrose, nucleotides and RNA in the production of proteins, starch and cell mass, and in the control of proliferation and cell growth are discussed. Furthermore, the importance of the maintenance pools for metabolic survival during starvation is emphasized. PMID- 24241610 TI - Origin and developmental changes of envelope proteins and translocator activities from plastids of Secale cereale L. AB - To determine the sites of synthesis of chloroplast-envelope proteins, we have analysed several enzyme and translocator functions ascribed to the envelope membranes, and investigated the envelope polypeptide composition of plastids isolated from 70S ribosome-deficient leaves of rye (Secale cereale L.) generated by growing the plants at a temperature of 32 degrees C. Since the ribosomedeficient plastids are also achlorophyllous in light-grown leaves, not only were chloroplasts from mature, green leaves used for comparison, but also those from yellowing, aged leaves as well as etioplasts from dark-grown leaves raised at a temperature of 22 degrees C. A majority of the plastidenvelope polypeptides appeared to be of cytoplasmic origin. The envelopes of ribosome deficient plastids possessed ATPase (EC 3.6.1.3) activity; this was not, however, dependent on divalent cations, in contrast to the Mn(2+)- or Mg(2+)-dependent ATPase which is associated with chloroplast envelopes. Adenylate kinase (EC 2.7.4.3) was present in the stromal fraction of ribosome-deficient plastids and the stromal form of this enzyme is, therefore, of cytoplasmic origin. In contrast to previous findings, adenylate kinase was not, however, specifically associated with the chloroplast-envelope membranes, either in rye or in spinach. Measurements of the uptake of L-[(14)C]-malate into ribosome-deficient plastids indicated the presence and cytoplasmic origin of the dicarboxylate translocator. Malate uptake into rye etioplasts was, however, low. The phosphate translocator was assayed by the uptake of 3-phospho-[(14)C]glycerate. While rapid 3 phosphoglycerate uptake was observed for rye chloroplasts and etioplasts, it was hardly detectable for ribosome-deficient, plastids and rather low for chloroplasts from aged leaves. A polypeptide of M r approx. 30000 ascribed to the phosphate translocator was greatly reduced in the envelope patterns of ribosome deficient plastids and of chloroplasts from aged leaves. PMID- 24241611 TI - Strategies for the selection and characterization of aluminum-resistant variants from cell cultures of Nicotiana plumbaginifolia. AB - The development of strategies for selecting and characterizing aluminum-resistant variants from Nicotiana plumbaginifolia Viv. cell cultures is described. Plated cells, smeared callus, in-vitro-grown shoots, and seedlings of wild-type N. plumbaginifolia all showed similar responses to Al, with total growth inhibition at or above 600 MUM Al. The strict control of both cell density and aggregate size is important in selection experiments for total inhibition of the growth of wild-type cells. Two approaches for the selection of Al-resistant variants were used. In a direct method, cells were plated onto medium containing 600 MUM Al which inhibited growth and chlorophyll synthesis in wildtype cells. A double selection strategy based on both cell growth and greening was used to isolate 29 Al-resistant variants. In the other approach, a rescue method, suspensions were cultured for 10 d in medium containing 600 MUM Al, then plated onto standard medium for recovery of survivors. Using this strategy, 217 Al-resistant variants were selected. After six to twelve weeks of growth in the absence of Al, each variant was cloned and reselected from single cells. Al resistance was retained in 31% and 51% of the variants selected by the direct and rescue strategies, respectively. Seedling segregation data are presented for the progeny (selfed and backcrossed) of plants regenerated from one of the variants and are consistent with those expected for a single dominant mutation. PMID- 24241612 TI - Degradation of the 32-kilodalton thylakoid-membrane polypeptide of Chlamydomonas reinhardi Y-1. AB - Isolated thylakoid membranes of Chlamydomonas reinhardi Y-1 with the 32-kDa polypeptide either radioactively labelled or unlabelled were incubated in vitro under various conditions in order to gain information about the degradation of the 32-kDa polypeptide. The degradation was higher at pH 6 compared with pH 7 and pH 8 and exhibited a temperature maximum between 20 degrees C and 25 degrees C (pH 6, pH 8). A light-dependent part of the total degradation was linearly dependent on white light of energy fluence rate between 1 and 20 mW.cm(-2) at 25 degrees C and leveled out at higher fluence rates. The degradation in light was only slightly stimulated by ATP but was reduced by 3-(3'-4'-dichlorophenyl)-1,1 dimethylurea. Adenosine-5'-diphosphate and heparin (2.7 mM and 200 MUg per 100 MUl, respectively) known to inhibit kinases, caused a 50% decrease in degradation indicating that a phosphorylation step is involved in degradating the 32-kDa polypeptide. Out of various inhibitors specific for different types of proteases, only those for thiol- and endoproteases showed intense effects. These results point to a proteolytic degradation of the 32-kDa polypetide by a thylakoid membrane-bound thiol-endoprotease. Its activity yields soluble breakdown products with relative molecular masses (Mrs) of 23, 16.5, 11.3 and 10.7 kDa, and these are accumulated in the in-vitro system. Partial proteolytic digestion of thylakoids with Staphylococcus aureus V8 protease results in at least two labelled breakdown products (Mrs 23, and 16.5 kDa). It is assumed that cleaving at identical amino-acid residues of the 32-kDa polypeptide by the thylakoid membrane-bound thiolendoprotease and the V8 protease results in these two breakdown products. They are derived from subsequent cleavage at amino-acid residues 60-242 and 60-189 according to the deduced protein sequence (Erickson et al. 1984, EMBO J. 3, 2753-2762). PMID- 24241613 TI - Abscisic acid, xanthoxin and violaxanthin in the caps of gravistimulated maize roots. AB - The occurrence and distribution of abscisic acid (ABA), xanthoxin (Xa) and the carotenoid violaxanthin (Va) were investigated in root tips of maize (Zea mays L. cv. Merit). In roots grown in the dark, Va and ABA were present in relatively high amounts in the root cap and in low amounts in the adjacent terminal 1.5 mm of the root. Xanthoxin was present in equal concentrations in both regions. In roots exposed to light, the ABA distribution was reversed, with relatively low levels in the root cap and high levels in the adjacent 1.5-mm segment. Light also caused a decrease in Va in both regions of the root and an increase in Xa, especially in the cap. In the maize cultivar used for this work, light is necessary for gravitropic curving. This response occurs within the same time frame as the light-induced ABA redistribution as well as the changes in the levels of Va and Xa. These data are consistent with a role for ABA in root gravitropism and support the proposal that Xa may arise from the turnover of Va. PMID- 24241614 TI - Potassium channels in Eremosphaera viridis : I. Influence of cations and pH on resting membrane potential and on an action-potential-like response. AB - The dependence of the membrane potential of Eremosphaera viridis on different external concentrations of potassium, sodium, calcium, and protons was compared with the diffusion potential measured in the dark and in the presence of NaN3. In contrast to some other algae, the membrane potential in the light as well as in the dark seemed to be predominantly determined by the calculated diffusion potential and less by an electrogenic pump which, however, seemed to be involved at potassium concentrations >1 mol.m(-3) and at higher pHos (>pH 6). Furthermore, some characteristics of an action-potential-like response (CAP) triggered by light-off, and independent of the membrane-potential threshold value, were determined. The CAP had a delay period of 5.4 s and needed 4.5 s for polarization to a plateau. On average, the plateau held for 8.8 s and the CAP lasted 37.7 s. The peak amplitudes of CAP (P AP) exactly followed the Nernst potential of potassium. Other cations like sodium, calcium and protons did not appreciably affect the peak amplitudes of CAP. From these and other results it can be assumed that the CAP is caused by a temporary opening of potassium channels in the plasma membrane of Eremosphaera (Kohler et al., 1983, Planta 159, 165-171). The release of a CAP by light-off has been partly explained by the participation of a transient increase of proton concentration in the cytoplasm. It was possible to trigger a CAP by external pH changes and by the addition of sodium acetate, thus supporting the hypothesis that a pH decrease in the cytoplasm may be one element of the signal transfer from the photosynthetic system to the potassium channels in the plasmalemma. Calcium also seemed to have an influence on triggering the CAP. PMID- 24241615 TI - Induction of de-novo synthesis of tryptophan decarboxylase in cell suspensions of Catharanthus roseus. AB - Tryptophan decarboxylase (EC 4.2.1.27) is synthesized de-novo by Catharanthus roseus cells shortly after the cells have been transferred into culture medium in which monoterpenoid indole alkaloids are formed. The enzyme production, monitored by in-vivo labelling with [(35)S]methionine and immunoprecipitation, precedes the apparent maximal enzyme activity by 10-12 h. From the time course of the descending enzyme activity after induction, a half-life of 21 h for tryptophan decarboxylase in C. roseus cell suspensions is calculated. A comparison of the polyadenylated-RNA preparations from C. roseus cells indicates that mRNA activity for tryptophan decarboxylase is only detected in cells grown in the production medium. The importance of tryptophan decarboxylase induction with respect to the accumulation of th corresponding alkaloids is discussed. PMID- 24241616 TI - Abscisic acid and the regulation of synthesis of specific seed proteins and their messenger RNAs during culture of soybean embryos. AB - The ability of soybean (Glycine max (L.) Merr.) embryos cultured in vitro in the absence of abscisic acid (ABA) to germinate precociously increased as the embryos matured. Exogenous ABA prevented precocious germination at all stages of development, concentrations below 10(-5) M being partially effective. Growth (fresh weight increase) of mid-maturation embryos was dependent on ABA, and such embryos required ABA for continued synthesis of storage proteins during culture. Two complementary-DNA clones for different members of the family of 11S storage proteins, and one for the 7S storage proteins were used in Northern blot hybridizations to analyze the effects of ABA on the levels of the 11S and 7S mRNAs. In addition, filter hybridizations with in-vivo-labeled [(3)H]polyadenylated RNA to the cloned DNA for one of the 11S proteins were carried out to study transcription of 11S mRNA. Midmaturation embryos cultured with ABA continued to transcribe mRNAs for the storage proteins during the 21 d of culture studied, whereas in the absence of ABA these mRNAs disappeared from the cotyledons within about 5 d. The optimum concentration of ABA for the synthesis of storage-protein mRNAs was 10(-5) M. The effect of ABA on the concentration of 11S mRNAs was stage-dependent. Abscisic acid caused a decrease in the mRNA in embryos cultured at the cotyledon stage; it was necessary for high levels of the mRNA to be achieved in early- and mid-maturation embryos; and it did not reverse the decline in the mRNA levels in embryos cultured at the late maturation stage. PMID- 24241617 TI - Characterization of calcium fluxes across the envelope of intact spinach chloroplasts. AB - Calcium fluxes across the envelope of intact spinach chloroplasts (Spinacia oleracea L.) in the light and in the dark were investigated using the metallochromic indicator arsenazo III. Light induces Ca(2+) influx into chloroplasts. The action spectrum of light-induced Ca(2+) influx and the inhibitory effect of 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) indicate an involement of photosynthetic electron transport in this process. The driving force for light-induced Ca(2+) influx is most likely a change in the membrane potential component of the proton motive force. This was demonstrated by the use of agents modifying the membrane potential (lipophilic cations, ionophores, different KCl concentrations). The activation energy of the observed Ca(2+) influx is about 92 kJ mol(-1). Verapamil and nifedipine, two Ca(2+)-channel blockers, have no inhibitory effect on light-induced Ca(2+) influx, but enhance ferricyanide-dependent oxygen evolution. Inhibition of Ca(2+) influx by ruthenium red reduces the light-dependent decrease in stromal NAD(+) level. PMID- 24241618 TI - Comparative quantitation of abscisic acid in plant extracts by gas-liquid chromatography and an enzyme-linked immunosorbent assay using the avidin-biotin system. AB - In this report we describe an enzyme-linked immunosorbent assay (ELISA) for the quantitation of abscisic acid (ABA) in plant extracts. A microtitration plate is coated with an ABA-protein complex. The ABA, standard or sample, is then added to each well with a limiting quantity of rabbit anti-ABA antibodies. During the following incubation period, antibodies bind either to free or to bound ABA on the plates. After washing, bound antibodies are indirectly labelled in two steps by the means of biotinylated goat antirabbit immunoglobulin-G antibodies which act as a link between rabbit anti-ABA antibodies and an avidin-alkaline phosphatase complex. The relative enzyme activity bound is measured spectrophotometrically. The detection limit of this method is 5 pg ABA and the measuring range extends to 10 ng. Gas-liquid-chromatography controls, with an electron capture detector, show a good correlation with ELISA results obtained using extracts of Lycopersicon esculentum, Nicotiana tabacum and Pseudotsuga menziesii samples purified by high-performance liquid chromatography. This provides a good argument for the accuracy of the immunoenzymatic method. The indirect labelling of antibodies, with the avidin-biotin amplifying system, should make this technique suitable for the quantitation of other plant growth substances against which specific antibodies are available. PMID- 24241619 TI - beta-Glucanases in developing cotton (Gossypium hirsutum L.) fibres. AB - Cotton fibres possess several beta-glucanase activities which appear to be associated with the cell wall, but which can be partially solubilised in buffers. The main activity detected was that of an exo-(1->3)-beta-D-glucanase (EC 3.2.1.58) but which also had the characteristics of a beta-glucosidase (EC 3.2.1.21). Endo-(1->3)-beta-D-glucanase activity (EC 3.2.1.39) and much lower levels of (1->4)-beta-D-glucanase activity were also detected. The exo-(1->3) beta-glucanase showed a maximum late on (40 days post-anthesis) in the development of the fibres, whereas the endo-(1->3)-beta-glucanase activity remained constant throughout fibre development. The beta-glucanase complex associated with the cotton-fibre cell wall also functions as a transglucosylase introducing, inter alia, (1->6)-beta-glucosyl linkages into the disaccharide cellobiose to give the trisaccharide 4-O-beta-gentiobiosylglucose. PMID- 24241620 TI - Alternative formation of anthraquinones and lipoquinones in heterotrophic and photoautotrophic cell suspension cultures of Morinda lucida Benth. AB - Photoheterotrophic and photoautotrophic cell suspension cultures were raised from a callus tissue derived from a Morinda lucida Benth. plant (Rubiaceae). The cultures were characterized with regard to fresh weight, dry weight, cell number, pH, chlorophyll and quinoid natural products. The amount of lipoquinones (phylloquinone, alpha-tocopherol, plastoquinone, ubiquinone) isolated from the photoautotrophic cultures matched the amount detected in an intact leaf. Anthraquinone glycosides which are found in the roots of Morinda plants were not present in the photoautotrophic culture. The photoheterotrophic culture contained only trace amounts of these pigments. Abundant anthraquinone synthesis was observed when photoautotrophic and photoheterotrophic suspension cultures were transferred into darkness, provided sucrose was present in the medium. Induction of synthesis of anthraquinone pigments coincided with a rapid disappearance of lipoquinones from the culture. Thus, in the suspension culture, photoautotrophy correlates with lipoquinone synthesis and heterotrophy correlates with anthraquinone synthesis. This reflects the situation in the intact plants where lipoquinones are chloroplast-associated whereas anthraquinones occur in the roots. PMID- 24241621 TI - The function of tonoplast ATPase in intact vacuoles of red beet is governed by direct and indirect ion effects. AB - The pH gradient and the electric potential across the tonoplast in mechanically isolated beetroot vacuoles has been studied by following the uptake of [(14)C]methylamine and [(14)C]triphenyl-methylphosphoniumchloride. In response to Mg-ATP, the vacuolar interior is acidified by 0.8 units. This strong acidification is accompanied by a slight hyperpolarization of the membrane potential, which is probably caused by a proton diffusion potential. In preparations where only a small acidification (0.4 units) occurred, the membrane potential was depolarized by the addition of Mg-ATP. Different monovalent cations and anions were tested concerning their effect on the pH gradient and ATPase activity in proton-conducting tonoplasts. Chloride stimulation and NO 3 (-) inhibition were clearly present. The observed decline of the pH gradient upon the addition of Na(+) salts is probably caused by an Na(+)/H(+) antiport system. PMID- 24241622 TI - The action of exogenous abscisic acid on malate-synthase synthesis in germinating castor-bean seeds. AB - The presence of 30 MUM abscisic acid inhibited development of malate-synthase activity in the endosperm of germinating castor-bean seeds. Malate synthase was purified from castor-bean endosperms and an antibody to it was prepared from rabbit serum. This antibody was used to measure the amounts of malate-synthase mRNA using an in-vitro translation system. The effect of abscisic acid appeared to be greater on malate-synthase mRNA than on the bulk of mRNA, indicating some specificity of abscisic-acid action. The extent of the inhibition of malate synthase activity and of malate-synthase mRNA accumulation were similar. This indicates that abscisic acid inhibits malate-synthase activity by lowering levels of translatable malate-synthase mRNA rather than by affecting the translation rate of this mRNA. PMID- 24241623 TI - Cell-wall-bound lytic activity in Chlorella fusca: function and characterization of an endo-mannanase. AB - A cell-wall-degrading activity was solubilized from young cells and from mother cell walls of Chlorella fusca by treatment with LiCl. The cytoplasmic enzyme hexokinase was not detectable in these extracts. The LiCl-solubilized activity increased in the cell cycle parallel to the release of autospores. The enzyme was purified on a chromatofocusing column followed by gel filtration. Sodium dodecyl sulfate/polyacryl amide gel electrophoresis of the purified enzyme revealed a molecular weight of 44 kDa, whereas gel filtration indicated a molecular weight of 25 kDa. Cell-wall-lytic activity and beta-1,4-mannanase activity coeluted in gel filtration and were separated from beta-D-fucosidase activity. The enzyme degraded isolated cell walls and ivory nut mannan primarily to oligosaccharides with an estimated degree of polymerization ?6. The soluble degradation products of the cell wall consisted of 92-96% mannose and 4-8% glucose. It is concluded that the cell-wall-lytic activity is caused by an endo-mannanase. In vivo, this enzyme probably degrades the mother cell wall and, after autospore release, remains bound to it as well as to the surface of the daughter cells by ionic forces. The identity of this bound enzyme with a soluble wall-degrading enzyme previously obtained from mother cells is discussed. PMID- 24241624 TI - cDNA-AFLP analysis reveals heat shock proteins play important roles in mediating cold, heat, and drought tolerance in Ammopiptanthus mongolicus. AB - Ammopiptanthus mongolicus (Maxim.ex kom.) Cheng F. is the only evergreen broadleaf shrub endemic to the desert of central Asian and it can survive at drought, salt, and alkali stress. It is believed that A. mongolicus is an important germplasm containing abiotic-tolerance genes. In order to identify drought-, cold-, and heat-responsive genes and to gain a better understanding of stress responses in A. mongolicus, genome-wide investigation of drought-, cold-, and heat-responsive genes was performed in A. mongolicus using cDNA-amplified fragment length polymorphism. Selective amplification with 240 primer combinations generated 5,000 differentially expressed transcript derived fragments (TDFs). Of these, 201 TDFs with differential expression patterns were excised from gels, reamplified by PCR, and sequenced. The gene expression patterns of 11 regulated genes were further investigated by semiquantitative reverse transcriptase polymerase chain reaction analysis. Sequencing and similarity analysis revealed that TDFs present homologies chiefly with proteins involved in various abiotic and biotic stress and developmental responses. The information presented in this study reveals that heat shock proteins play an active role in mediating drought, cold, and heat tolerance in A. mongolicus. PMID- 24241625 TI - The use of the isotropic orientation factor in fluorescence resonance energy transfer (FRET) studies of the actin filament. AB - A Dale-Eisinger style analysis (R. E. Daleet al., Biophys. J. 26, 161, 1979) is used to produce three-dimensional plots that display the limits on the average orientation factor [Symbol: see text]K (2)[Symbol: see text] that is required to calculate molecular distances in F-actin from fluorescence resonance energy transfer measurements. Maxima and minima plots are generated for the transfer of energy from a donor to a single acceptor and for transfer to multiple acceptors that are related by F-actin helical symmetry. The analysis is performed in terms of dipole cone half-angles rather than depolarization factors, in order to facilitate the modeling of the multiple acceptor problem. Calculations are carried out under the restrictive condition of a single electric dipole moment per fluorophore. In addition, both surface and volume averaging of the donor and acceptor dipoles are considered. Comparisons between the plots show that for the multiple acceptor cases with F-actin symmetry, there is a great reduction in the range for maxima and minima limits on [Symbol: see text]K (2)[Symbol: see text]. The calculations also suggest guidelines for the choice of fluorescence label that will result in an average orientation factor occurring within acceptable limits, i.e., inside the limits for which [Symbol: see text]K (2)[Symbol: see text]=2/3 may be employed. Thus, without having detailed knowledge of the mean donor or acceptor dipole relative orientations, the use of [Symbol: see text]K (2)[Symbol: see text]=2/3 in radial coordinate studies of F-actin is more than reasonable and is fairly assured of being correct. PMID- 24241626 TI - Tryptophan phosphorescence of ribonuclease T1 as a probe of protein flexibility. AB - The phosphorescence properties of Trp-59 of ribonuclease T1 fromAspergillus oryzae were monitored as a function of temperature, pH, salt concentration, and complex formation with substrate analogues and, also, in the presence of glycerol as viscogenic cosolvent. The results establish a rough correlation between the internal flexibility of the macromolecule, as derived from the triplet lifetime, and its stability (DeltaG orT m ) toward unfolding. Below 10 degrees C or in 70% glycerol the triplet probe distinguishes at least two gross conformations for the protein, which are characterized by a large difference in phosphorescence lifetime. It is pointed out that such structural heterogeneity does not correspond with the heterogeneity inferred from fluorescence decays and acrylamide quenching rates. Further, implications of the phosphorescence data with regard to the interpretation of acrylamide quenching of fluorescence are discussed. PMID- 24241627 TI - Packing of phospholipid vesicles studied by oxygen quenching of Laurdan fluorescence. AB - Steady-state fluorescence oxygen quenching experiments were performed on phospholipid vesicles where 2-dimethylamino-6-lauroylnaphthalene (Laurdan) was inserted. The quenching efficiency was found to be much higher in vesicles in the liquid-crystalline phase with respect to the gel phase, by a factor of about 50. Since the oxygen solubility in the two phospholipid phases can differ at most by a factor of 4 based on literature values, we concluded that oxygen diffusion must be responsible for the great difference in the quenching efficiency. A relatively high quenching efficiency was also found in vesicles composed of equimolar gel and liquid-crystalline phospholipids. Simulations were performed using the linear superposition of the properties of the pure phases to demonstrate that, in the case of vesicles composed of coexisting phases, the diffusional properties of oxygen in each phase are largely modified by the presence of the other. The addition of 10 mol% cholesterol to the gel phase rendered Laurdan fluorescence approximately as quenchable as in the equimolar mixture of the two phases. This result points out that molecules such as cholesterol, which introduce packing defects in the bilayer, favor oxygen diffusion. From the oxygen quenching experiments and using the properties of generalized polarization, the rate of Laurdan dipolar relaxation can be estimated. PMID- 24241628 TI - Electronic spectra of dye solutions. I. The mirror image rule. AB - The main assumptions of the quasi-molecule model of electronic spectra of liquid dye solutions are presented. The derived analytical expressions of the spectra account for the solvatochromic effects present in the solution. Based on the obtained spectral profiles of some coumarins in alcohol, new criteria for the validity of the mirror image rule are formulated. PMID- 24241629 TI - The DNA content of mouse two-cell embryos can be measured by microfluorimetric image analysis under conditions of cell viability. AB - Video-enhanced fluorescence imaging was used to quantify the DNA content in live two-cell mouse embryos. DNA was stained with the vital fluorophore Hoechst 33342. Conditions of dye concentration and irradiation were such that two-cell embryos could be kept in the constant presence of the dye for about 24 h without a major effect on their furtherin vitro viability. Total nuclear fluorescence intensity of stained two-cell embryos was measured twice under these conditions, i.e., in G1 (1 h after cleavage) and in G2 (15-18 h after cleavage), by image analysis. After correcting for the fluctuations in excitation intensity and for the spatial nonhomogeneities of the optical system (lenses and sensor), the mean total nuclear fluorescence intensity was about twofold higher in G2 than in G1 ([Symbol: see text]R[Symbol: see text]=1.99 to 2.25), and this increase was abolished by the addition of aphidicolin, an inhibitor of replication. The fluorescence increase did not depend on the Hoechst concentration in the range of 10-40 ng/ml, i.e., in the range of embryo viability. The coefficient of variation of the total nuclear fluorescence intensity measured under these conditions was rather large (10 to 20%). Nevertheless, the mean value of fluorescence intensity in G1 of nuclei of a given pool represents an appropriate reference to measure the increase in fluorescence intensity between G1 and G2. PMID- 24241630 TI - Calibration methods and avoidance of errors in measurement of intracellular pH (pHcyt) using the indicator bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) in human platelets. AB - Determinations of pHcyt in suspensions of human platelets using BCECF [bis(carboxyethyl)-5(6)-carboxyfluorescein] can be seriously biased by leakage of the fluorescent indicator. Two methods ("pH jump" and "Mn(2+)") are presented for determining the fraction of external indicator (B ext) and eliminating this error. Both methods rely on rapid perturbations (pH jump or Mn(2+) addition), which affect the fluorescence of the external dye immediately and the intracellular dye more slowly. Identical values ofB ext are reported. Failure to correct for dye leakage can result in overestimation of pHcyt by as much as 0.4 unit at physiological external pH (pHext). Two methods of calibration of the cytoplasmic signal were compared after correcting forB ext: the "digitonin lysis" method and the "nigericin calibration" method. In the digitonin method the dye is released at the end of the experiment and the dependence of its fluorescence is determined as a function of pH. The method assumes that the fluorescence and titration characteristics of the dye in the cytoplasm are not different from those in solution. It gives pHcyt=6.75+/-0.07 for pHext=7.3. In the nigericin method, 150 mM external K(+) and 10 MUM nigericin are used for the purpose of setting pHcyt=pHext to accomplish anin situ calibration. The method was complicated by extra leakage induced by nigericin. Assuming that the ionophore could equilibrate pH in the alkaline range, the fluorescence of the anionic form of BCECF in the cytoplasm would be 15% lower than in solution and pHcyt would be 0.3 unit higher than presented above. A number of observations favor the digitonin lysis method of calibration. The fluorescence polarization of BCECF in platelets is small and indistinguishable from that in solution (0.000+/-0.022). The spectrofluorimetric characteristics of the intracellular dye are identical to those in solution (150 mM NaCl or KCl). There was no evidence for self-quenching or binding to cellular elements for cytoplasmic BCECF concentrations up to 1.8 mM. The following agents are capable of introducing error: (1) the Na(+) substituteN-methyl-D-glucamine doubles theK d and decreases by 13% the DeltaF max of BCECF; (2) the Na(+)/H(+) exchange inhibitor amiloride quenches BCECF fluorescence and is intrinsically fluorescent; and (3) bovine serum albumin (used to remove nigericin) quenches external BCECF with kinetics mimicking acidification of the cytoplasm. PMID- 24241631 TI - Erratum. PMID- 24241633 TI - Network medicine: finding the links to personalized therapy. AB - Network medicine is a new approach that focuses on applying systems biology to pharmacology by "understanding the molecular system [and its perturbations] as a whole" so as to unravel the complex relationships among disease processes, genes, drugs, therapeutic indicators, and adverse effects.(1,2.) PMID- 24241637 TI - Network medicine in disease analysis and therapeutics. AB - Two parallel trends are occurring in drug discovery. The first is that we are moving away from a symptom-based disease classification system to a system based on molecules and molecular states. The second is that we are shifting from targeting a single molecule toward targeting multiple molecules, pathways, or networks. Network medicine is an approach to understanding disease and discovering therapeutics looking at many molecules and how they interrelate, and it may play a critical role in the adoption of both trends. PMID- 24241638 TI - Managing the risk of drug-induced liver injury. AB - In clinical trials, bosentan was shown to cause significant drug-induced liver injury (DILI) in some patients. Because it is not possible to identify those at higher risk for DILI, all patients to be treated with bosentan must enroll in a program requiring documentation of liver blood testing before they can receive the drug. Because this program is costly and is perceived as onerous, a genetic test capable of identifying susceptible individuals would probably be rapidly adopted by physicians. PMID- 24241639 TI - Challenges in interpreting the evidence for genetic predictors of ototoxicity. AB - There has been recent controversy regarding predictors of cisplatin-induced ototoxicity in children, as highlighted in a previous issue of this journal. We have reviewed the two articles that purport to show an association between TPMT and COMT variants and ototoxicity, as well as the related patent applications dating back to 2006. We summarize statistical issues not fully addressed by the authors that appear to have confounded the results of their studies. PMID- 24241641 TI - Experimental determination of the spatial scale of a prey patch from the predator's perspective. AB - Foraging theory predicts that predators should prefer foraging in habitat patches with higher prey densities. However, density depends on the spatial scale at which a "patch" is defined by an observer. Ecologists strive to measure prey densities at the same scale that predators do, but many natural landscapes lack obvious, well-defined prey patches. Thus one must determine the scale at which predators define patches of prey. We estimated the scale at which guppies, Poecilia reticulata, selected patches of zooplankton prey using a behavioral assay. Guppies could choose between two prey arrays, each manipulated to have a density that depended on the spatial scale at which density was calculated. We estimated the scale of guppy foraging by comparing guppy preferences across a series of trials in which we systematically varied the scale associated with "high" prey density. This approach enables the application of foraging theory to non-discrete habitats and prey landscapes. PMID- 24241640 TI - Advancing biodiversity-ecosystem functioning science using high-density tree based experiments over functional diversity gradients. AB - Increasing concern about loss of biodiversity and its effects on ecosystem functioning has triggered a series of manipulative experiments worldwide, which have demonstrated a general trend for ecosystem functioning to increase with diversity. General mechanisms proposed to explain diversity effects include complementary resource use and invoke a key role for species' functional traits. The actual mechanisms by which complementary resource use occurs remain, however, poorly understood, as well as whether they apply to tree-dominated ecosystems. Here we present an experimental approach offering multiple innovative aspects to the field of biodiversity-ecosystem functioning (BEF) research. The International Diversity Experiment Network with Trees (IDENT) allows research to be conducted at several hierarchical levels within individuals, neighborhoods, and communities. The network investigates questions related to intraspecific trait variation, complementarity, and environmental stress. The goal of IDENT is to identify some of the mechanisms through which individuals and species interact to promote coexistence and the complementary use of resources. IDENT includes several implemented and planned sites in North America and Europe, and uses a replicated design of high-density tree plots of fixed species-richness levels varying in functional diversity (FD). The design reduces the space and time needed for trees to interact allowing a thorough set of mixtures varying over different diversity gradients (specific, functional, phylogenetic) and environmental conditions (e.g., water stress) to be tested in the field. The intention of this paper is to share the experience in designing FD-focused BEF experiments with trees, to favor collaborations and expand the network to different conditions. PMID- 24241642 TI - Chenopod salt bladders deter insect herbivores. AB - Trichomes on leaves and stems of certain chenopods (Chenopodiaceae) are modified with a greatly enlarged apical cell (a salt bladder), containing a huge central vacuole. These structures may aid in the extreme salt tolerance of many species by concentrating salts in the vacuole. Bladders eventually burst, covering the leaf in residue of bladder membranes and solid precipitates. The presence of this system in non-halophytic species suggests additional functions. I tested the novel hypothesis that these bladders have a defensive function against insect herbivores using choice, no choice, and field tests. Generalist insect herbivores preferred to feed on leaves without salt bladders in choice tests. In no choice tests, herbivores consumed less leaf matter with bladders. In a field test, leaves from which I had removed bladders suffered greater herbivory than adjacent leaves with bladders. Solutions containing bladders added to otherwise preferred leaves deterred herbivores, suggesting a water-soluble chemical component to the defense. This bladder system has a defensive function in at least four genera of chenopods. Salt bladders may be a structural defense, like spines or domatia, but also have a chemical defense component. PMID- 24241643 TI - Consistent proportional increments in responses of belowground net primary productivity to long-term warming and clipping at various soil depths in a tallgrass prairie. AB - Root distribution patterns in soil are critical to understanding the interactions between climate and vegetation. However, it is not clear how climate change and land use practices affect belowground net primary productivity (BNPP) at various soil depths. In order to explore the effects of warming and clipping on root distribution patterns along soil profile (0-15, 15-30, and 30-45 cm), we conducted a field experiment from 2005 to 2010 in a tallgrass prairie. We used infrared heaters to elevate soil temperature by approximately 2 degrees C and annual clipping to mimic hay harvest. Results showed that roots were not evenly distributed through the soil profile. On average across treatments and years, 53 and 83% of the BNPP to 45 cm was distributed in the top 15- and 30-cm soil layers, respectively. Warming- and clipping-induced increases in BNPP were distributed to different soil depths at the proportions similar to those of BNPP. The proportional distribution of BNPP at various soil depths to total BNPP (0-45 cm) was little affected by warming, clipping, and their interactions, resulting in non-significant changes in the distribution of BNPP through the soil profile. These findings suggest that the proportionally vertical distribution of BNPP may remain stable even when the amount of BNPP changes simultaneously in response to climate change and land use practices. PMID- 24241644 TI - The use of lichen growth abnormalities as an early warning indicator of forest dieback. AB - Combinations of pollutants including acidic fog and ozone occur at high levels at a number of sites in eastern North America and Europe. Mountainous regions such as the Laurentians (Quebec), Appalachians (N.Y.) and the Green Mountains (Vermont) are especially vulnerable, with both conifers and hardwoods being affected. Ongoing measurements of atmospheric chemistry (e.g. The Chemistry of High Elevation Fog-CHEF project of the Canadian Atmospheric Environment Service) reveal that extreme cloudwater events of less than pH 3.0 and ozone episodes in excess of 100 ppb are common occurrences. The purpose of this study was to gather information about the response of epiphytic lichens to deteriorating air quality at selected locations for which atmospheric chemical data are readily available. A multidisciplinary approach is being used to analyse the lichens.Morphological and cellular aberrations previously documented by the authors to occur in terricolous lichens exposed to simulated acidic rain events will be evaluated for their usefulness are early warning indicators of forest decline. In addition, tissue chemistry of species such as Hypogymnia physodes will be correlated with parameters such as altitude and decline index and compared with published elemental values for lichens from similarly polluted sites in Europe and Scandinavia. PMID- 24241645 TI - Freshwater avain and mammalian predators as indicators of aquatic environmental quality. PMID- 24241646 TI - Public participation and volunteer help in monitoring programs: An assessment. AB - A number of opportunities exist for involving the public in environmental monitoring. This paper outlines some examples where this has been done, evaluates these examples, and then summarizes some of the benefits as well as the disadvantages of this approach. PMID- 24241647 TI - Monitoring the condition of the Canadian forest environment: The relevance of the concept of 'ecological indicators'. AB - The Canadian forest environment is characterized by high spatial and temporal variability, especially in the west. Our forests vary according to climate, landform, and surficial geology, and according to the type, intensity, extent of, and the time since the last disturbance. Most Canadian forests have had a history of repeated acute, episodic disturbance from fire, insects, wind, diseases and/or logging, with a frequency of disturbance varying from a few decades to many centuries. These sources of variability have resulted in a complex and continually changing mosaic of forest conditions and stages of successional development.Monitoring the 'quality' of this dynamic forested landscape mosaic is extremely difficult, and in most cases the concept of a relatively simple index of forest ecosystem quality or condition (i.e. an 'ecological indicator') is probably inappropriate. Such ecological indicators are better suited for monitoring chronic anthropogenically induced disturbances that are continuous in their effect (e.g. 'acid rain', heavy metal pollution, air pollution, and the 'greenhouse effect') in ecosystems that, in the absence of such chronic disturbance, exhibit very slow directional change (e.g. lakes, higher order streams and rivers). Monitoring the effects of a chronic anthropogenic disturbance to forest ecosystems to determine if it is resulting in a sustained, directional alteration of environmental 'quality' will require a definition of the expected pattern of episodic disturbance and recovery therefrom (i.e. patterns of secondary succession in the absence of the chronic disturbance). Only when we have such a 'temporal fingerprint' of forest ecosystem condition for 'normal' patterns of disturbance and recovery can we determine if the ecosystem condition is being degraded by chronic human-induced alteration of the environment. Thus, degradation is assessed in terms of deviations from the expected temporal pattern of conditions rather than in terms of an instantaneous assessment of any particular condition. The concept of 'ecological rotation' (the time for a given ecosystem to recover from a given disturbance back to some defined successional condition) is useful in the definition of these 'temporal fingerprints'. This requires information on the intensity of disturbance, the frequency of disturbance, and the rate of successional recovery. Only when all three of these are known or estimated can statements be made as to whether the ecosystem is in a longterm sustainable condition or not.The somewhat overwhelming complexity of this task has led forest ecologists to use ecosystem-level computer simulation models. Appropriately structured and calibrated models of this type can provide predictions of the overall temporal patterns of ecosystem structure and functions that can be expected to accompany a given frequency and character of episodic disturbance. Such models can also be used to examine the long-term consequences of chronic disturbances such as acid rain and climatic change. Predictive ecosystem-level models should be used in conjunction with some method of stratifying the inherent spatial biophysical variability of the forest environment, such as the biogeoclimatic classification system of British Columbia. PMID- 24241648 TI - Indicators of ecosystem health at the species level and the example of selenium effects on fish. AB - Chemical monitoring of aquatic ecosystems describes the chemical exposures of aquatic biota and measures the success of pollution control. However, meeting water quality criteria cannot assure that aquatic biota are protected from the effects of unexpected chemicals, mixtures and interactions between toxicity and environmental stressors.Biological monitoring is an obvious solution since aquatic biota integrate spatial and temporal variations in exposure to many simultaneous stressors. Top predators, typical of specific ecosystems (e.g. lake trout in cold water oligotrophic lakes) indicate whether environmental criteria have been met. The presence of naturally reproducing, self-sustaining and productive stocks of edible fish demonstrates a high quality environment. If these conditions are not met, there is a clear sign of environmental degradation. Specific changes in population structure and performance may also diagnose which life stage is affected and the nature of the stressor.Unfortunately, environmental managers cannot rely solely on populations, communities or ecosystems to indicate chmical effects. The lag between identifying a problem and finding a cause may destroy the resource that we wish to protect, particularly where chemicals are persistent.A solution to this dilemma is the measurement of primary or secondary responses of individual organisms to chemical exposure. Since toxicity at any level of organization must start with a reaction between a chemical and a biological substrate, these responses are the most sensitive and earliest sign of chemical exposure and effect.Application of this idea requires research on molecular mechanisms of chemical toxicity in aquatic biota and adaptation of existing mammalian diagnostic tools. Since relevance of biochemical responses to populations and ecosystems is not obvious, there is a need to study the links between chemical exposure and responses of individuals, populations and ecosystems.The recognition of chemical problems and cause-effect relationships requires the integration of chemical and biological monitoring, using the principles of epidemiology to test the strength of relationships and to identify specific research needs. The contamination of a reservoir with selenium and impacts on fish populations provide an excellent example of this approach. PMID- 24241649 TI - Water quality indices as indicators of ecosystem change. AB - The operational management of water quality requires a methodology that can provide precise information on cycles and trends in water quality in an objective and reproducible manner. Such information can be provided by the adoption of a water quality indexing system. The continuous scale afforded by a water quality index allows changes in river water quality to be highlighted. At the same time the sub-division of this scale into a series of water quality and water use categories provides an easy means of relating information to government and public.The development of four independent water quality indices (WQIs) is outlined. These have been applied to data for a number of UK river reaches. The results of these applications indicate the utility of these indices in the classification of water quality and the monitoring of ecosystem change. PMID- 24241650 TI - Redistribution of Cesium-137 as an example of a chemical indicator of environmental stress. AB - The use of the artificially-produced radioactive isotope Cesium-137 for the measurement of soil erosion is examined in this article as an example of the development of a chemical indicator of a specific environmental stress. The theoretical and methodological bases of the technique ar examined in the context of seven criteria developed to assess the suitability of a technique as a chemical indicator. The type of results available from the application of the technique are demonstrated for research in agricultural ecosystems in Saskatchewan, Canada. The research indicates that mean soil losses within agricultural fields are 2 to 3 times higher than the tolerable soil losses for the area and that net soil export from fields is a poor indicator of the intensity of erosion within the field. The major remaining constraint to the use of the technique is the lack of a standardized sampling and analytical framework for researchers using the procedure. PMID- 24241651 TI - Workgroup issue paper: Criteria for ecological indicators : Introduction. PMID- 24241652 TI - Rapporteur's report of work group: Indicators at the species and biochemical level. PMID- 24241653 TI - Workgroup issue paper: Community or ecosystem level indicators : Introduction to indicators at the community or ecosystem level. PMID- 24241654 TI - Rapporteur's report of work group: Indicators at community or systems level. PMID- 24241655 TI - Workgroup issue paper: Introduction to chemical indicators, using the example of soil chemistry as applied to agriculture. PMID- 24241656 TI - Rapporteur's report of work group: Chemical indicators. PMID- 24241657 TI - Workgroup issue paper: Indicators and assessment of the state of fisheries. PMID- 24241658 TI - Rapporteur's report of work group: Indicators and assessment of the state of fisheries. PMID- 24241659 TI - Workgroup issue paper: Indicators and assessment of the state of forests : Introduction to Assessment of Forests. PMID- 24241660 TI - Rapporteur's report of work group: Indicators and assessment on the state of forest. PMID- 24241661 TI - Workgroup issue paper: Indicators and assessment of agricultural sustainability : Methods of Assessing Agricultural Sustainability. AB - Sustainability is emerging as one of the most fundamental concepts for assessing the overall state of an agricultural production system. Essentially, this concept assumes that if a production system is sustainable indefinitely, then it is acceptable. But almost any system is sustainable if sufficient resources are committed to it! So it's obvious that an uncritical adoption of the idea is not acceptable. PMID- 24241662 TI - Rapporteur's report of work group: Indicators and assessment of agricultural sustainability. PMID- 24241663 TI - Editorial. PMID- 24241664 TI - Significant improvement of androgenetic haploid and doubled haploid induction from wheat plants treated with a chemical hybridization agent. AB - A very significant improvement of the total yield of androgenetic green plants after anther culture is presented. The process involves treatment of the donor plants by spraying at different stages around the meiosis with a chemical hybridization agent (CHA) solution, fenridazon-potassium. When harvested at the normal uninucleate pollen grain stage, anthers have shown during in vitro culture very significant increases in embryo production. Compared to the control, we observed up to a 20-fold increase in the production. Moreover, when cultivated later, anthers still remained embryogenic. Therefore the process appears to be very efficient and to allow a broadening of the target period for androgenesis in vitro. The regeneration was not disturbed by the CHA treatment and, as shown in this paper, the technique seems to be applicable to a large range of genotypes. Cytological observations revealed both a low frequency of aneuploidy among the regenerated plants and peculiar features in the pollen grain walls after treatments; a triploid plant was observed. Hypotheses to explain the phenomenon are presented and related to previous observations on the effects of gametocide substances like ethrel, male sterility and pollen dimorphism on androgenesis. PMID- 24241666 TI - Analysis of organelle genomes in a somatic hybrid derived from cytoplasmic male sterile Brassica oleracea and atrazine-resistant B. campestris. AB - An atrazine-resistant, male-fertile Brassica napus plant was synthesized by fusion of protoplasts from the diploid species B. oleracea and B. campestris. Leaf protoplasts from B. oleracea var. italica carrying the Ogura male-sterile cytoplasm derived from Raphanus sativus were fused with etiolated hypocotyl protoplasts of atrazine-resistant B. campestris. The selection procedure was based on the inability of B. campestris protoplasts to regenerate in the media used, and the reduction of light-induced growth of B. oleracea tissue by atrazine. A somatic hybrid plant that differed in morphology from both B. oleracea and B. campestris was regenerated on medium containing 50 MUM atrazine. Its chromosome number was 36-38, approximately that of B. napus. Furthermore, nuclear ribosomal DNA from this hybrid was a mixture of both parental rDNAs. Southern blot analyses of chloroplast DNA and an assay involving tetrazolium blue indicated that the hybrid contained atrazine-resistant B. campestris chloroplasts. The hybrid's mitochondrial genome was recombinant, containing fragments unique to each parent, as well as novel fragments carrying putative crossover points. Although the plant was female-sterile, it was successfully used to pollinate B. napus. PMID- 24241665 TI - Chloroplast DNA variation in the grass tribe Festuceae. AB - Six grasses, Hordeum sativum, Dactylis glomerata, Festuca arundinacea, F. pratensis, F. rubra and Lolium multiflorum were subjected to chloroplast DNA analysis based on restriction endonuclease digestion fragments and end labeling with (35)S nucleotides. This method is compared with others in general use. The results indicate that Lolium multiflorum is closely affiliated with Festuca pratensis and F. arundinacea; in fact much closer than F. rubra is to any of them. PMID- 24241667 TI - Interrelationships among stabilities of important agronomic traits in sugarcane. AB - The stability-variance statistic, gs i (2) , measures the contribution of the i(th) genotype to genotype x environment interaction. In addition to the knowledge of cultivar stability for an agronomic trait, information on whether stability of one trait can be used to predict stability of another should be useful to breeders. Three separate groups of data, respectively involving CP 79 series, CP 80 series, and CP 81 series experimental clones of sugarcane (Saccharum spp.) were used in this study. Rank-correlation coefficients (rs) between ranks of genotypes for gs i (2) 's for paired traits indicated in both plant-cane and ratoon crops that stability of tons per hectare of sugar can be predicted from the stability of tons per hectare of cane (THC) and also, to a lesser extent, from the stability of stalk number. The stability of THC also can be reasonably well predicted from the stability of stalk number. Brix stability may give some indication of the stabilities for percentage sucrose and sugar concentration (SC). The gs i (2) 's for percentage sucrose and SC were almost identical in the CP 79 and CP 81 series (rs varied from 0.93, P<0.01, in plant cane crop for CP 79 series to 0.98, P<0.01, in plant-cane crop for CP 81 series). Whether correlations were based on gs i (2) 's estimated across locations within crops or across crops, the magnitude of rs was about the same. Means of various traits were not correlated with their respective gs i (2) 's (for CP 81 series), indicating that identification and selection of high-yielding sugarcane genotypes with a relatively high degree of stability of performance across test environments should be possible. PMID- 24241668 TI - Male transmission of the translocated chromosome in a tertiary trisomic of rye: genetic variation and relation to the rate of development of aneuploid pollen grains. AB - Variation in male and female transmission of the translocated extra chromosome (5R(3R)) was studied in a tertiary trisomic of rye (Secale cereale L.). In two F5 lines derived from a single F4 line, female transmission was lower than in five others derived from another F4 line. This could be caused by genetic factors or by the strong inbreeding depression in these lines, leading to low viability of trisomic progeny. After selfing, male transmission was estimated as very low, but this was primarily based on the occurrence of tetrasomics that probably have a very poor viability. In testcrosses with disomic female parents, male transmission was much higher (up to 27%), without variation within F5 lines. One F5 line showed significantly higher male transmission than any of the seven tested, including a sister line from the same F4. This was consistent in the F6. Apparently high male transmission is genetically determined. There was a positive correlation with recombination of the marker ti (tigrina) on the extra chromosome and the normal 5R chromosomes. At the first meiotic metaphase, trivalents and quinquivalents were frequent in the trisomics. Assuming loss of univalents, 40% of the microspores should carry the translocated extra chromosome. In most lines, more than 40% were found at pollen mitosis. Observations on timing of pollen mitosis showed a delayed development in aneuploid spores, with clear differences between plants, but no correlation with male transmission. The cause of reduced male transmission and the expression of genetic variation therein can, therefore, not be found in meiotic behaviour or delayed microspore development. Pollen germination and tube growth may be more important. PMID- 24241669 TI - The addition of Dasypyrum villosum (L.) Candargy chromosomes to durum wheat (Triticum durum Desf.). AB - Six monosomic addition lines were produced in which different Dasypyrum villosum (L.) Candargy chromosomes were added to the chromosome complement of Triticum durum Desf. cv. 'Creso'. Each added alien chromosome was found to have a specific effect on plant morphology and fertility. Transmission rate varied widely (from 7.5 to 27.7%) among the six univalent chromosomes. Different monotelosomic addition plants derived by a relatively high frequency of chromosome misdivision were isolated. The addition lines should be useful for studying Dasypyrum chromosome homoeology and the introduction of alien variation into durum and common wheats. PMID- 24241670 TI - Genetic analysis of the anther-culture response of three spring wheat crosses. AB - Anther-culture response was examined among three spring wheat (Triticum aestivum L.) cultivars to evaluate the genetic component of response and to determine whether androgenetic performance could be improved by selection. The three lines, the three possible F1's among the three lines, their F2's, and the backcrosses to the parents were evaluated for callus production and regeneration capacity. Significant variation was observed among the generations of the three crosses for callus formation. Genetic variation for regenerability was nonsignificant. Callus production was negatively correlated (-0.24) with regeneration capacity. The random variation in the study was too great to determine whether major-gene differences for antherculture response exist among the three lines by examining population distributions. When the material was evaluated for quantitative gene effects, the estimates for the additive gene effects were generally greater than the estimates for the dominance gene effects for callus formation. Only the Pavon x Chris cross, however, exhibited a significant narrow sense heritability estimate for callusing response (0.94). Due to the large component of random variation and the varying selection potential among crosses for androgenetic performance, improving anther-culture response in wheat by selection could prove difficult unless the anther-culture process itself selects for response traits at the gametic level. PMID- 24241671 TI - Optimum prediction of three-way crosses from single crosses in forage maize (Zea mays L.). AB - Three-way cross means were predicted with formulae involving linear functions of general (GCA) and specific combining ability (SCA) effects estimated from single cross factorials between genetically divergent populations. Data from an experiment with 66 single-cross and 66 three-way cross forage maize (Zea mays L.) hybrids was used for comparing the prediction formulae. The genotypic correlation (r) between observed and predicted three-way crosses increased with increasing chi, the weighting factor of SCA effects, for plant height and ear dry matter (DM) content. It displayed slightly convex curves for total and stover DM yield, ear percentage, and metabolizable energy content of stover. For Jenkins' method B, r was considerably less than 1.0 for all traits, indicating the presence of epistasis. The square root of heritability (hG) of the predicted means decreased with increasing chi, the reduction being small with a greater number of test environments. Using the product r.hG as a criterion of efficiency, none of the prediction methods was consistently superior and the differences among them were rather small (< 7.5%) for all traits, irrespective of the number of test environments. We recommend evaluating the GCA of a greater number of lines from each parent population in testcrosses with a small number of elite lines from the opposite population. All possible three-way or double crosses between both sets of lines should be predicted by Jenkins's method C. This procedure allows one to select with a higher intensity among the predicted hybrids and thus should increase the genetic gain. PMID- 24241672 TI - Five primary trisomics from translocation heterozygote progenies in common bean, Phaseolus vulgaris L. AB - Twelve distinct phenotypic groups of plants were isolated from nondisjunction progenies of 11 translocation heterozygote stocks. All the plants in these phenotypic groups originated in the light weight seed class. Five of the 12 phenotypic groups of plants have been verified as primary trisomics. They are all phenotypically distinguishable from each other and from disomics. One of the five primary trisomic groups, puckered leaf, was directly recovered as a primary trisomic from the original translocation heterozygote progenies. Three of the five trisomics - weak stem, dark green leaf, and convex leaf - originated first as tertiary trisomics. The related primary trisomics were isolated later from progenies of selfed tertiary trisomics. The fifth group, chlorotic leaf, originated at a low frequency among the progenies of three other trisomics: puckered leaf, convex leaf, and dark green leaf. The chlorotic leaf did not set seed under field conditions. The remaining four groups - puckered leaf, dark green leaf, convex leaf, and weak stem - are fertile, though sensitive to high temperature conditions. The transmission rate of the extra chromosome on selfing ranges from 28% to 41%. Physical identification of the extra chromosome has not been achieved for any of the five trisomic groups. Two trisomic groups, dark green leaf and convex leaf, have produced tetrasomics at low frequency. The phenotypes of these two tetrasomics are similar to the corresponding trisomics but more exaggerated. PMID- 24241673 TI - Multivariate analysis and the choice of parents for hybridization in Okra (Abelmoschus esculentus (L.) Moench). AB - Thirty okra genotypes of diverse eco-geographical origin were grown in single-row plots in a randomised complete block design. The data collected on 14 characters were subjected to analysis of variance. By multivariate analysis (Mahalanobis D(2) technique), the genetic divergence among the genotypes were quantitatively measured. The genotypes were grouped into five clusters by this technique. There was no relationship between clustering pattern and eco-geographic distribution. The effects of genetic divergence on the choice of parental stock in hybridization was discussed. PMID- 24241674 TI - Somatic hybridization in potato: use of gamma-irradiated protoplasts of Solanum pinnatisectum in genetic reconstruction. AB - Leaf mesophyll protoplasts of Solanum pinnatisectum (2n=24) gamma-irradiated at doses of 200 Gy and consequently unable to divide were fused with untreated protoplasts of genomic chlorophyll deficient mutant IvP 841-1 (2n=24) containing the germplasms of S. tuberosum and S. phureja. Two types of plants differing in their pigmentation characteristics were selected. The regenerants of one group were identified as true somatic hybrids by using isozyme analyses of esterase and aspartate aminotransferase. The anthocyanin marker of S. pinnatisectum was phenotypically expressed in these regenerants and could be used as an additional selection trait for hybrid screening in this species combination. The regenerants of the second group were corrected for the gene controlling chlorophyll deficiency but contained species-specific isozymes of the potato cultivar only. Restriction analysis of chloroplast DNA revealed chloroplasts of the S. pinnatisectum type in all but one of the plants tested. The fusion experiments involving gamma-irradiated protoplasts show that this approach in potato reconstruction has the advantage of producing a wide range of genetically novel plants. PMID- 24241675 TI - Cloning quantitative trait loci by insertional mutagenesis. AB - This study explores the theoretical potential of "insertional mutagenesis" (i.e., mutagenesis as a result of integration of novel DNA sequences into the germ line), as a means of cloning quantitative trait loci (QTL). The approach presented is based on a direct search for mutagenic effects of a quantitative nature, and makes no assumptions as to the nature of the loci affecting quantitative trait value. Since there are a very large number of potential insertion sites in the genome but only a limited number of target sites that can affect any particular trait, large numbers of inserts will have to be generated and screened. The effects of allelic variants at any single QTL on phenotype value are expected to be small relative to sampling variation. Thus two of three stages of replicate testing will be required for each insert in order to bring overall Type I error down to negligible proportions and yet maintain good statistical power for inserts with true effects on the quantitative traits under consideration. The overall effort involved will depend on the spectrum of mutagenic effects produced by insertional mutagenesis. This spectrum is presently unknown, but using reasonable estimates, about 10,000 inserts would have to be tested, at reasonable replicate numbers (n ? 30) and Type I error (alpha=0.01) in the first testing stage, to provide a high likelihood of detecting at least one insert with a true effect on a given quantitative trait of interest. Total offspring numbers required per true quantitative mutagenic effect detected decrease strongly with increased number of traits scored and increased number of inserts per initial transformed parent. In fact, it would appear that successful implementation of experiments of this sort will require the introduction of multiple independent inserts in the original parent individuals, by means of repeated transformation, or use of transposable elements as inserts. When biologically feasible, selfing would appear to be the method of choice for insert replication, and in all cases the experiments must be carried out in inbred lines to reduce error variation due to genetic segregation, and avoid confounding mutational effects of the insert with effects due to linkage with nearby segregating QTL. The special qualifications of Arabidopsis thaliana for studies of this sort are emphasized, and problems raised by somaclonal variation are discussed. PMID- 24241676 TI - Origin of gynodioecy in Limnanthes: evidence from ecogeographic patterns of variation. AB - Evidence for hybrid origin of gene-cytoplasmic gynodioecy in Limnanthes douglasii is presented in terms of the parapatric distributions of putative parental taxa and the increased levels of genetic variation in gynodioecious populations. Attempts to produce gynodioecy through artificial hybridization between different accessions apparently failed due to the limited number of parental combinations used in making hybrids. Further studies are proposed on the hybrid origin model and on selective forces determining the fate of gynodioecy with its contributions to higher levels of hybridity and genetic variation. PMID- 24241677 TI - Genetic control of dipeptidase in the Triticeae. AB - Isoelectric focusing has been employed to elucidate the genetic control of a series of dipeptidase isozymes in wheat and its relatives. The phenotype of wheat shows four bands, three of which are shown by aneuploid analysis to be controlled by the loci Dip-A1, Dip-B1 and Dip-D1 on chromosome arms 6AL, 6BL and 6DL, respectively. Varietal polymorphism for Dip-A1 and Dip-B1 was observed. Different homoeoloci were found in barley, Haynaldia villosa and Agropyron junceum. PMID- 24241678 TI - Intersubgeneric hybridization of soybeans with a wild perennial species, Glycine clandestina Wendl. AB - The exploitation of wild perennial species of subgenus Glycine has been formidable in soybean breeding programs because of extremely poor crossability and an early pod abortion. The combination of gibberellic acid application to hybridized gynoecia and improved seed culture media formulations resulted in a new intersubgeneric hybrid between Glycine max (L.) Merr. (2n=40) and G. clandestina Wendt. (2n=40). Of the 31 immature seeds cultured, 1 regenerated 21 plants through organogenesis while the remaining 30 failed to germinate. All the regenerated plants were similar morphologically, carried expected 2n=40, possessed hybrid isozyme patterns and were completely sterile. Complete absence of chromosome pairing was observed in 40.9% sporocytes. The occurrence of 1 to 6 loosely paired rod bivalents suggests some possibilities of allosyndetic pairing. Hybrid plants set aborted pods after backcrossing to G. max. PMID- 24241679 TI - The relationship between the concepts of genetic diversity and differentiation. AB - Diversity as a measure of individual variation within a population is widely agreed to reflect the number of different types in the population, taking into account their frequencies. In contrast, differentiation measures variation between two or more populations, demes or subpopulations. As such, it is based on the relative frequencies of types within these subpopulations and, ideally, measures the average distance of subpopulations from their respective lumped remainders. This concept of subpopulation differentiation can be applied consistently to a single population by regarding each individual as a deme (subpopulation) of its own, and it results in a measure of population differentiation delta T which depends on the relative frequencies of the types and the population size. delta T corresponds to several indices of variation frequently applied in population genetics and ecology, and it verifies these indices as measures of differentiation rather than diversity. For any particular frequency distribution of types, the diversity nu is then shown to be the size of a hypothetical population in which each type is represented exactly once, i. e. for which delta T =1. Hence, the diversity of a population is its differentiation effective number of types. This uniquely specifies the link between the two concepts. Moreover, nu again corresponds to known measures of diversity applied in population genetics and ecology. While population differentiation can always be estimated from samples, the diversity of a population, particularly if it is large, may not be. In such cases, it is recommended that population differentiation is estimated and the corresponding sample diversity merely computed. Finally, a solution to the problem of measuring multi-locus diversities is provided. PMID- 24241680 TI - Investigation of partial sterility in advanced generation, sodium azide-induced lines of spring barley. AB - The partial sterility found in several advanced generation, sodium azide-induced lines of spring barley (Hordeum vulgare L.) was investigated. Plants of mutant lines were reciprocally crossed with plants of their untreated mother lines. Spike sterility was measured in the selfed offspring of the plants crossed and in F1 and F2 progeny. Pollen sterility and endosperm development were analyzed in the selfed offspring of the plants crossed. Results indicated that the sterility was inherited in the mutant lines and was not caused by translocations, inversions, endosperm lethals, embryo-endosperm lethals, or major gene mutations. Furthermore, the sterility was not cytoplasmically inherited, and was essentially eliminated in the F1 and F2 of crosses between partially sterile lines and their fertile parents. Results suggest that the sterility may be caused by an environmental interaction with deleterious, homozygous recessive, minor gene mutations that were in the heterozygous condition when the mutant lines were originally selected. PMID- 24241681 TI - Analysis of lethals in selected lines of Drosophila melanogaster. AB - Five lines of Drosophila melanogaster that reached an extreme phenotype after long-term selection for increased dorsocentral bristle number, were analysed for the presence of lethals. Seven chromosome II and three chromosome III lethal types were detected in four of the lines, at frequencies ranging from between 6% and 36%. No lethal had any demonstrable effect over the selected trait. In one line, where almost every chromosome II was a lethal carrier, it was shown that the main lethal (at a frequency of 36%) was associated with the transmission ratio distortion in males. The processes which could lead to the accumulation of this lethal and others linked in disequilibrium to it is discussed. Some results suggest similar mechanisms for the accumulation of lethals in the other lines. These findings show that causes other than the direct effect of artificial selection must be taken into account when trying to explain the accumulation of lethals in selected lines. PMID- 24241682 TI - Identification of loop nucleotide polymorphisms affecting microRNA processing and function. AB - MicroRNAs are short 21-22 nucleotide single strand RNAs that are involved in post transcriptional regulation of gene expression. Most microRNAs are first transcribed as long primary microRNAs and then undergo a two step-wise sequential processing to yield single-stranded mature microRNAs. It has been suggested that the loop region of primary microRNAs plays an important role in regulating microRNA biogenesis and target recognition. However, despite the fact that several single nucleotide polymorphisms have been identified in mature microRNA sequences and are related to human diseases, it remains unclear whether and how the single nucleotide polymorphisms in the loop regions of primary microRNAs would affect the biogenesis and function of microRNAs. Herein, we provide evidence that primary microRNAs loop nucleotides control the accuracy and efficiency of microRNA processing. Accordingly, we identified 32 single nucleotide polymorphisms in the loop regions of human primary microRNAs using bioinformatics, and further validated three loss-of-function and one gain-of function single nucleotide polymorphisms using dual-luciferase assays. Thus, these results reveal a critical regulatory role encoded in the loop nucleotides of primary microRNAs for microRNA processing and function. PMID- 24241683 TI - SMURF1 plays a role in EGF-induced breast cancer cell migration and invasion. AB - Epidermal growth factor (EGF) is a well-known growth factor that induces cancer cell migration and invasion. Previous studies have shown that SMAD ubiquitination regulatory factor 1 (SMURF1), an E3 ubiquitin ligase, regulates cell motility by inducing RhoA degradation. Therefore, we examined the role of SMURF1 in EGF induced cell migration and invasion using MDA-MB-231 cells, a human breast cancer cell line. EGF increased SMURF1 expression at both the mRNA and protein levels. All ErbB family members were expressed in MDA-MB-231 cells and receptor tyrosine kinase inhibitors specific for the EGF receptor (EGFR) or ErbB2 blocked the EGF mediated induction of SMURF1 expression. Within the signaling pathways examined, ERK1/2 and protein kinase C activity were required for EGF-induced SMURF1 expression. The overexpression of constitutively active MEK1 increased the SMURF1 to levels similar to those induced by EGF. SMURF1 induction by EGF treatment or by the overexpression of MEK1 or SMURF1 resulted in enhanced cell migration and invasion, whereas SMURF1 knockdown suppressed EGF- or MEK1-induced cell migration and invasion. EGF treatment or SMURF1 overexpression decreased the endogenous RhoA protein levels. The overexpression of constitutively active RhoA prevented EGF- or SMURF1-induced cell migration and invasion. These results suggest that EGFinduced SMURF1 plays a role in breast cancer cell migration and invasion through the downregulation of RhoA. PMID- 24241685 TI - Animal-type melanoma: report of five cases with sentinel node biopsy and fluorescence in-situ hybridization analysis. AB - Animal-type melanoma (ATM) is a rare tumor, characterized histologically by a predominantly dermal proliferation of heavily pigmented epithelioid and spindle dendritic melanocytes. Five patients with ATM, who had undergone sentinel node biopsy, were studied: three male and two female, between 4 and 62 years of age (mean, 28.0). Lesion size ranged from 4 to 18 mm and thickness from 0.7 to 5.1 mm. Nodal deposits were found in three patients. Of the patients with positive sentinel nodes, the first showed a minimal nodal involvement in one node, the second multiple deposits in one node, and the third multiple deposits in one sentinel node and a single deposit in another; this last patient also had additional tumor deposits in a nonsentinel regional node. Fluorescence in-situ hybridization tumor analysis proved negative in all cases. All patients are alive and free of disease at 36-95-month follow-up (mean, 53 months). Results showed ATM as a neoplasm characterized by a somewhat high rate of lymph node involvement but relatively low rate of visceral metastases and mortality, appearing as a low grade malignant tumor. PMID- 24241684 TI - Novel in vitro culture condition improves the stemness of human dermal stem/progenitor cells. AB - Cell therapy using adult stem cells has emerged as a potentially new approach for the treatment of various diseases. Therefore, it is an essential procedure to maintain the stemness of adult stem cells for clinical treatment. We previously reported that human dermal stem/progenitor cells (hDSPCs) can be enriched using collagen type IV. However, hDSPCs gradually lose their stem cell properties as in vitro passages continue. In the present study, we developed optimized in vitro culture condition to improve the stemness of these hDSPCs. To evaluate whether the stemness of hDSPCs is well sustained in various culture conditions, we measured the expression levels of SOX2, NANOG, and S100B, which are well-known representative dermal progenitor markers. We observed that hDSPCs grown in three dimensional (3D) culture condition had higher expression levels of those markers compared with hDSPCs grown in two-dimensional (2D) culture condition. Under the 3D culture condition, we further demonstrated that a high glucose (4.5 g/L) concentration enhanced the expression levels of the dermal progenitor markers, whereas O(2) concentration did not affect. We also found that skin-derived precursor (SKP) culture medium was the most effective, among various culture media, in increasing the dermal progenitor marker expression. We finally demonstrated that this optimized culture condition enhanced the expression level of human telomerase reverse transcriptase (hTERT), the proliferation, and the multipotency of hDSPCs, an important characteristic of stem cells. Taken together, these results suggested that this novel in vitro culture condition improves the stemness of hDSPCs. PMID- 24241686 TI - Vemurafenib in the French temporary authorization for use metastatic melanoma cohort: a single-centre trial. AB - Vemurafenib, a selective BRAF inhibitor, has recently shown an improved overall survival (OS) in metastatic melanoma with V600E mutation in phase 2 and 3 trials. Patients with BRAF V600E metastatic melanoma received vemurafenib orally, in the French temporary authorization for use program from April 2011 to April 2012. We analysed the clinical benefit and safety of vemurafenib. Secondary analyses included the impact of brain metastases on median OS and progression-free survival (PFS). Fifty patients were enrolled, of whom 20% had stage IIIC and 80% stage IV disease. The majority were men (58%), with a median age of 58 years (51 69). Forty-three patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 (86%). Twenty patients had brain metastases (40%). Overall response rate was 53%. Complete response was achieved in five patients (10%), partial response in 21 patients (43%) and stable disease in seven patients (14%). Median OS was 7.5 months (95% confidence interval 5.6-12.7) and PFS was 3.6 months (95% confidence interval 2.9-5.9). Patients with brain metastasis had a response rate of 50% (nine partial response, one complete response), and median OS and PFS were, respectively, 4.3 and 3.1 months. Common adverse events were fatigue, arthralgia and cutaneous side effects. Sixteen per cent developed squamous cell carcinoma. Grade 3/4 was observed in 11 patients (22%). Six per cent required temporary discontinuation and/or dose reduction because of toxic effects. This study confirms the considerable clinical benefit of vemurafenib for patients with brain metastasis, with manageable toxicity. PMID- 24241687 TI - The amphetamine sensitization model of schizophrenia symptoms and its effect on schedule-induced polydipsia in the rat. AB - RATIONALE: Amphetamine enhances dopamine (DA) transmission and induces psychotic states or exacerbates psychosis in at-risk individuals. Amphetamine sensitization of the DA system has been proposed as a rodent model of schizophrenia-like symptoms. In humans, excessive nonphysiologic drinking or primary polydipsia is significantly associated with a diagnosis of schizophrenia. In rodents, nonphysiologic drinking can be induced by intermittent presentation of food in the presence of a drinking spout to a hungry animal; this phenomenon is termed, "schedule-induced polydipsia" (SIP). OBJECTIVE: This study aims to determine the effects of amphetamine sensitization on SIP. METHODS: We injected rats with amphetamine (1.5 mg/kg) daily for 5 days. Following 4 weeks of withdrawal, animals were food restricted and exposed to the SIP protocol (noncontingent fixed time 1-min food schedule) for daily 2-h sessions for 24 days. RESULTS: Results showed that previously amphetamine-injected animals drank more in the SIP protocol and drank more than controls when the intermittent food presentation schedule was removed. CONCLUSIONS: These findings suggest that hyperdopaminergia associated with schizophrenia may contribute to the development of polydipsia in this population. Whether animals that develop SIP have DA dysfunction or aberrant activity of other circuits that modulate DA activity has yet to be clearly defined. PMID- 24241688 TI - Appropriate amino acid mixtures for tryptophan depletion and tyrosine/phenylalanine depletion and the safety of long-term amino acid depletion in humans: reply. PMID- 24241690 TI - Optically enhanced charge transfer between C60 and single-wall carbon nanotubes in hybrid electronic devices. AB - In this article we probe the nature of electronic interactions between the components of hybrid C60-carbon nanotube structures. Utilizing an aromatic mediator we selectively attach C60 molecules to carbon nanotube field-effect transistor devices. Structural characterization via atomic force and transmission electron microscopy confirm the selectivity of this attachment. Charge transfer from the carbon nanotube to the C60 molecules is evidenced by a blue shift of the Raman G(+) peak position and increased threshold voltage of the transistor transfer characteristics. We estimate this charge transfer to increase the device density of holes per unit length by up to 0.85 nm(-1) and demonstrate further optically enhanced charge transfer which increases the hole density by an additional 0.16 nm(-1). PMID- 24241689 TI - Cholesterol in mild cognitive impairment and Alzheimer's disease in a birth cohort over 14 years. AB - Animal epidemiological and clinical studies suggest that cholesterol is a risk factor for Alzheimer's disease (AD). Nevertheless, the relation of cholesterol to mild cognitive impairment (MCI), influence of APOE genotype and its changes in lifespan is controversial. We investigated the potential impact of plasma total cholesterol (TC) on development of MCI and AD in the interdisciplinary longitudinal study on adult development and aging, a representative birth cohort (born 1930-1932), examined in 1993/1994 (VT1), 1997/1998 (VT2), and 2005/2007 (VT3). Of 500 participants at baseline, 381 survived and were examined at VT3. After exclusion of participants with lifetime prevalence of major psychiatric diseases or mild cognitive disorder due to a medical condition, 222 participants were included in the analysis. At VT3, 82 participants had MCI, 22 participants had AD, and 118 were in good health. Participants with MCI and AD at VT3 evidenced higher TC levels at VT1 than those who were healthy. Higher TC levels at baseline were associated with an increased risk for cognitive disorders at VT3 (highest vs. lowest quartile: OR 2.64, 95 % CI 1.12-6.23, p < 0.05). Over the 14 year follow-up, TC levels declined in those with MCI and AD, but remained stable in those who remained healthy. These findings were not modified by APOE genotype or use of cholesterol-lowering medications. Our findings demonstrate that higher TC levels are observed long before the clinical manifestation of MCI and AD in patients without psychiatric or somatic comorbidities and are independent of APOE genotype. PMID- 24241691 TI - Full-length novel MHC class I allele discovery by next-generation sequencing: two platforms are better than one. AB - Deep sequencing has revolutionized major histocompatibility complex (MHC) class I analysis of nonhuman primates by enabling high-throughput, economical, and comprehensive genotyping. Full-length MHC class I cDNA sequences, which are required to generate reagents such as MHC-peptide tetramers, cannot be directly obtained by short read deep sequencing. We combined data from two next-generation sequencing platforms to discover novel full-length MHC class I mRNA/cDNA transcripts in Chinese rhesus macaques. We first genotyped macaques by Roche/454 pyrosequencing using a 530-bp amplicon spanning the densely polymorphic exons 2 through 4 of the MHC class I loci that encode the peptide-binding region. We then mapped short paired-end 250 bp Illumina sequence reads spanning the full-length transcript to each 530-bp amplicon at high stringency and used paired-end information to reconstruct full-length allele sequences. We characterized 65 full length sequences from six Chinese rhesus macaques. Overall, approximately 70 % of the alleles distinguished in these six animals contained new sequence information, including 29 novel transcripts. The flexibility of this approach should make full-length MHC class I allele genotyping accessible for any nonhuman primate population of interest. We are currently optimizing this method for full length characterization of other highly polymorphic, duplicated loci such as the MHC class II DRB and killer immunoglobulin-like receptors. We anticipate that this method will facilitate rapid expansion and near completion of sequence libraries of polymorphic loci, such as MHC class I, within a few years. PMID- 24241692 TI - The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. AB - IFNL3, which encodes interferon-lambda3 (IFN-lambda3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 3' untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability. We found that this polymorphism influenced AU-rich element (ARE)-mediated decay (AMD) of IFNL3 mRNA, as well as the binding of HCV-induced microRNAs during infection. Together these pathways mediated robust repression of the unfavorable IFNL3 polymorphism. Our data reveal a previously unknown mechanism by which HCV attenuates the antiviral response and indicate new potential therapeutic targets for HCV treatment. PMID- 24241694 TI - (E)-11,13-tetradecadienal: Major sex pheromone component of the eastern blackheaded budworm,Acleris variana (Fern.) (Lepidoptera: Tortricidae). AB - (E)-11,13-Tetradecadienal (E11,13-14:Ald) is the major sex pheromone component of the eastern blackheaded budworm (EBB),Acleris variana (Fern.). The compound was identified in female pheromone gland extracts by coupled gas chromatographic electroantennographic detection (GC-EAD), coupled GC-mass spectrometry in selected ion monitoring mode, and retention index calculations of candidate pheromone components.E11,13-14:Ald alone as trap bait was very attractive to male EBB. Addition of the corresponding diene alcohol or acetate or both did not enhance attraction. (Z)-11,13-Tetradecadienal in binary combination with (E) 11,13-14:Ald neither enhanced nor reduced trap catches. Increasing the amounts of pheromone from 0.01 to 10 ug increased trap catches, but increase of pheromone quantity above 100 ug proportionately reduced attraction. Stabilization of slowly polymerizingE11,13-14:Ald and development of a sustained, adequate release rate is required for pheromone-based monitoring of EBB populations. PMID- 24241695 TI - Attraction of female mediterranean fruit flies to the five major components of male-produced pheromone in a laboratory flight tunnel. AB - Attraction and pheromonal activity of five major identified components of the male-produced sex pheromone of the Mediterranean fruit flyCeratitis capitata to virgin laboratory-reared females was assessed in a laboratory flight tunnel. Dual choice competitive assays were run to establish a baseline response of virgin females to live male pheromone, individual components, and an ensemble of all five compounds alone (air control) and competitively against one another. Approximately 50% of the females released in the tunnel were captured on leaf models emitting pheromonal odors from five live males. Over 37% of released females responded to an ensemble of five major identified components presented in individual capillaries. Response of females to individual components was less than 10%. Competitive assays showed the live male-produced pheromone to be more attractive than either the five major component ensemble (FMCE) or individual components. Further research is likely to identify other male-produced compounds with pheromonal activity that could improve development of a pheromone-based trap for monitoring Mediterranean fruit fly populations. PMID- 24241693 TI - Innate-like T cells straddle innate and adaptive immunity by altering antigen receptor responsiveness. AB - The subclassification of immunology into innate and adaptive immunity is challenged by innate-like T lymphocytes that use innate receptors to respond rapidly to stress despite expressing T cell antigen receptors (TCRs), a hallmark of adaptive immunity. In studies that explain how such cells can straddle innate and adaptive immunity, we found that signaling via antigen receptors, whose conventional role is to facilitate clonal T cell activation, was critical for the development of innate-like T cells but then was rapidly attenuated, which accommodated the cells' innate responsiveness. These findings permitted the identification of a previously unknown innate-like T cell subset and indicate that T cell hyporesponsiveness, a state traditionally linked to tolerance, may be fundamental to T cells entering the innate compartment and thereby providing lymphoid stress surveillance. PMID- 24241696 TI - Phytotoxic substances in root exudates of cucumber (Cucumis sativus L.). AB - The addition of activated charcoal to a nutrient solution for the hydroponic culture of cucumber resulted in significant increases in the dry weight of the plant and fruit yield. Hydrophobic root exudates were collected at different growth stages with Amberlite XAD-4 resin and bioassayed with lettuce seedlings. The exudates at the reproductive stage were more phytotoxic than those at the vegetative stage. The exudates contained organic acids such as benzoic,p hydroxybenzoic, 2,5-dihydroxybenzoic, 3-phenylpropionic, cinnamic,p hydroxycinnamic, myristic, palmitic, and stearic acids, as well asp thiocyanatophenol and 2-hydroxybenzothiazole, all of which, except 2 hydroxybenzothiazole, were toxic to the growth of lettuce. PMID- 24241697 TI - Control of plant-parasitic nematodes by a nematicidal strain ofAspergillus niger. AB - An isolate ofAspergillus niger (designated PD-42) was evaluated in laboratory, greenhouse, and field trials for efficacy in controlling plant-parasitic nematodes. In greenhouse experiments, PD-42 drenches containing spores of PD-42 on oatmeal significantly reduced galling on tomato due to root-knot nematode as compared to untreated controls. In a one-half acre field experiment, PD-42 incorporated in seed coats was associated with significantly increased yield and decreased root-knot galling on pepper. In a second one-half acre field experiment, PD-42 drenches significantly reduced tomato and pepper root galling due toMeloidogyne incognita, and nonsignificant yield increases occurred. In each field experiment, treatment with PD-42 reducedRotylenchulus reniformis populations. The nematicidal components of theA. niger culture filtrates include citric acid, oxalic acid, and undetermined molecules larger than 8000 MW. PMID- 24241699 TI - Flight-mediated attraction ofBiprorulus bibax breddin (Hemiptera: Pentatomidae) to natural and synthetic aggregation pheromone. AB - The attraction of female spined citrus bugs,Biprorulus bibax, to natural and synthetic aggregation pheromone was studied using an olfactometer and a large flight cage. No locomotory response by postdiapause, prereproductive females to heptane extracts of male dorsal abdominal glands (DAGs) (site of pheromone production) was recorded in the olfactometer study. However, postdiapause, prereproductive females showed significant attraction to sites baited with DAG extracts in the flight cage (1.9-3.0 times that of unbaited sites). Prereproductive and reproductive females showed greatest attraction to sites baited with a synthetic blend of pheromone [(3R,4S,1'E-3,4-bis(1' butenyl)tetrahydro-2-furanol, linalool, farnesol, nerolidol] (2.3-4.7 times the attraction of unbaited sites). Females also responded significantly to sites baited with the hemiacetal major component alone (1.7-2.2*). Diapausing females collected from fall populations did not respond to natural or synthetic pheromone baits. Potential applications of the synthetic aggregation pheromone are discussed with respect toB. bibax management. PMID- 24241698 TI - Changes in pheromone titer of oblique-banded leafroller,Choristoneura rosaceana, virgin females as a function of time of day, age, and temperature. AB - Under a 16:8 hr light-dark photoperiod and 20?C constant temperature, the titers of (Z)-11-tetradecenyl acetate (Z11-14:Ac), (E)-11-tetradecenyl acetate (E11 14:Ac) and (Z)-11-tetradecenol (Z11-14:OH) produced by different agedChoristoneura rosaceana virgin females varied significantly during the scotophase, with the maximum titer occurring before the onset of calling in day-0 and day-3 females, while in day-5 females the titer remained constant throughout the calling period. There was a significant decrease in the titer of all pheromone components with age, explaining the lesser attractiveness of day-5 females relative to day-0 and day-3 females observed in the field. Under a cold thermocycle simulating condition during the second flight period in the fall, the titers of all pheromone components did not vary with time of day. There was a significant decrease in the amount ofZ11-14:Ac with age but no changes occurred in the minor components. Furthermore, for any given age tested, the amount of each component produced during the period of maximal calling activity remained relatively similar at the two temperature regimes. However, as with the expression of calling behavior, pheromone production was initiated earlier at cooler than at warmer temperatures. At both temperature regimes, female age and time of day influenced the ratio of each pheromone component. These results are discussed in relation to the hypothesis that by calling earlier, less attractive older females may increase their probability of mating. PMID- 24241700 TI - Prior exposure to carbaryl alters behavior ofTetranychus urticae Koch on acaricide-treated leaf surfaces. AB - Preadult exposure to carbaryl affected the subsequent behavior of two-spotted spider mites (Tetranychus urticae Koch) on leaf surfaces with discontinuous acaricide residues. In dicofol bioassays, preexposure to carbaryl caused a loss of avoidance behavior (eliminating the tendency of mites to feed and stand longer off treated areas). In amitraz bioassays, preexposure to carbaryl had the opposite effect. It increased the propensity of mites to feed and stand off amitraz-treated areas, resulting in increased avoidance of amitraz. Carbaryl preexposure therefore resulted in diametrically opposed behavioral changes in subsequent encounters with two acaricides. These effects provide additional evidence of the unpredictable nature of interactions between pesticides and show how a chemical, irrespective of degree of toxicity, can alter the behavior of arthropods in response to subsequent chemical encounters. PMID- 24241702 TI - Aggregation pheromones inDryocoetes affaber (Mann.) (Coleoptera: Scolytidae): stereoisomerism and species specificity. AB - Chemical analysis of whole body extracts and volatiles produced by feeding malesDryocoetes affaber (Mann.) disclosed (+)-exo-brevicomin and (+)-endo brevicomin [(+)EXOB and (+)ENDOB], as the major insect-produced potential pheromones. Laboratory bioassays and field-trapping experiments demonstrated that (+)ENDOB is the main pheromone component, and (-)ENDOB has an inhibiting effect. EXOB either as (+) or (+/-) appears to be a multifunctional pheromone. It has a synergistic effect in blends of EXOB and ENDOB in ratios up to 1:1, and it is inhibitory at higher ratios. (-)EXOB was inactive. The most attractive blend forD. affaber was a 1:2 blend of (+)EXOB and (+)ENDOB. When this blend was compared with a 9:1 blend, the best known blend forDryocoetes confusus Swaine, the responses by beetles of each of the two species were highly specific, providing evidence for pheromonal exclusion between the two congenerics. We conclude that the combined effect of chirality and the ratio of geometrical isomers of brevicomin determines both the level of response and the species specificity of the chemical signal inD. affaber. PMID- 24241701 TI - Pheromone differences between sibling taxaDiachrysia chrysitis (linnaeus, 1758) andD. tutti (Kostrowicki, 1961) (Lepidoptera: Noctuidae). AB - The noctuid sibling taxaDiachrysia chrysitis s. str. andD. tutti, of yet uncertain taxonomic status, have previously been shown to possess differences in morphology and to be attracted to different mixtures of the two presumed pheromone components (Z)-5-decenyl acetate and (Z)-7-decenyl acetate. TypicalD. tutti males (clearly broken forewing marking) are known to respond to a 2: 100 mixture of the two isomers, whereasD. chrysitis males (unbroken marking) are attracted to a 100: 10 mixture. We investigated female pheromone production and male electroantennographic (EAG) response inDiachrysia families raised in the laboratory from field-collected gravid females. Extracts of individual females from typicalD. tutti andD. chrysitis families were subjected to gas chromatography with simultaneous flame ionization and electroantennographic detection. All females produced mixtures of Z5- and Z7-10:OAc, but femaleD. chrysitis produced predominantly Z5-10:OAc and the antennae of their brothers responded more strongly to the Z5 peak than to the Z7-10:OAc peak, whereas the opposite was true forD. tutti families. The pheromone components were shown to be biosynthesized from hexadecanoic and tetradecanoic acid, respectively by Z11 desaturation followed by chain shortening, reduction, and acetylation. The EAG responses of males trapped with the typicalD. tutti andD. chrysitis blends, as well as with an intermediate blend, were investigated. Males trapped with theD. tutti mixture almost exclusively had a clearly broken wing marking and showed strongest EAG response to Z7-10:OAc. The intermediate blend and theD. chrysitis mixture gave more mixed catches, but with a prevalence of males with an unbroken (or almost unbroken) wing marking and with a higher mean response to Z5-10:OAc. Some males with typicalD. tutti EAG responses were attracted in the field to theD. chrysitis pheromone. In the flight tunnel someD. chrysitis males were attracted also to theD. tutti mixture. This indicates that cross attraction may take place between the two taxa under natural conditions. PMID- 24241704 TI - Uscharin, the most potent molluscicidal compound tested against land snails. AB - Calotropis procera, is a shrub with broad ovate fleshy leaves that grows wild in the Egyptian deserts. The plant was discovered to be highly toxic to the land snailsThepa pisana. The active ingredient responsible for the molluscicidal activity was isolated from its latex by solvent extraction and partitioning and was finally purified by fractional crystallization from 95% aqueous ethanol. The purity of the isolated material was monitored by TLC. Chemical identification was carried out using mass, infrared, and proton magnetic resonance spectroscopic methods. The active compound was found to be uscharin, and its identity was confirmed by comparing its spectroscopic data with the literature values. The isolated compound was 128 times more toxic than methomyl to the snails tested. PMID- 24241703 TI - Different feeding and gustatory responses to ecdysone and 20-hydroxyecdysone by larvae of the silkworm,Bombyx mori. AB - The feeding and gustatory responses to ecdysone and 20-hydroxyecdysone were investigated in the silkworm,Bombyx mori. 20-Hydroxyecdysone reduced feeding response strongly in fourth- and fifth-instar larvae, whereas ecdysone had no effect on feeding response. 20-Hydroxyecdysone stimulated the R receptor, the receptor to feeding deterrents, to a great degree. By contrast, ecdysone was much less effective for stimulating the R receptor. These results indicate that ecdysone and 20-hydroxyecdysone have different effects on feeding response due to different interactions with mouthpart chemoreceptors. PMID- 24241705 TI - Sex pheromone activity in a single component of tergal gland extract ofLutzomyia longipalpis (Diptera: Psychodidae) from Jacobina, Northeastern Brazil. AB - The sex pheromone component of maleLutzomyia longipalpis tergal gland extract was isolated and its activity confirmed by bioassay. Whole tergal gland extract was analyzed by HPLC and fractions were collected as they eluted from the detector. Each fraction was tested in an attraction bioassay with virgin unfed femaleLutzomyia longipalpis. HPLC analysis showed that whole extract contained several peaks; one large peak, one small peak and several minor peaks. Purity of the HPLC fractions was determined by GC analysis. The bioassays revealed that the large peak was responsible for most of the observed female behavior. The addition of the small peak to the large peak improved the response although by itself the small peak failed to elicit any significant behavior. Minor peaks failed to elicit any response. Chemical analysis revealed the large peak to be a relatively nonpolar hydrocarbon. PMID- 24241706 TI - Pheromonal secretions from glands on the 5th abdominal sternite of hydropsychid and rhyacophilid caddisflies (Trichoptera). AB - Extracts of different body parts of adult Trichoptera were tested for electrophysiological activity. Extracts of the IVth and Vth abdominal sternites of femaleHydropsyche angustipennis, Rhyacophila nubila, andR. fasciata, containing a paired exocrine gland, elicited significant electroan-tennographic responses when tested on conspecific male antennae. The paired gland occurs also in males of all the species, and inH. angustipennis, extracts from males were more active than female extracts when tested on male antennae. Female and male extracts from all species were analyzed by gas chromatography with simultaneous flame ionization and electroantennographic detection (EAD). EAD-active peaks in female extracts, stimulating male antennae, were identified inH. angustipennis as nonan-2-one; and inR. nubila andR. fasciata as heptan-2-one, heptan-2-ol, nonan-2 one, and nonan-2-ol. EAD-active components from maleH. angustipennis stimulating male antennae were octan-2-one, nonan-2-one (major peak), (Z)-6-nonen-2-one, decan-2-one, and a methylbranched decan-2-one. Female extracts and synthetic mixtures of compounds identified from femaleH. angustipennis andR. fasciata were tested for attractivity in the field. High catches with control traps obscured the results, but a synthetic mixture of the four identified compounds was significantly attractive and not different from female extracts for attracting maleR. fasciata. InH. angustipennis, a synthetic six-component male blend, in which nonan-2-one was the major component, attracted significant numbers of male and femaleH. angustipennis. Extracts of maleR. nubila andR. fasciata contained acetophenone and hexanoic and octanoic acids but did not have any electrophysiological or behavioral activity on either male or female antennae of conspecifics. The occurrence of a female sex pheromone inRhyacophila and an aggregation pheromone inHydropsyche corresponds to earlier described differences in mating behaviors in the Rhyacophilidae and Hydropsychidae. PMID- 24241707 TI - Codling moth (Cydia pomonella): Disruptants of sex pheromonal communication. AB - In a small section of an apple orchard, six traps were placed each in control and test areas and baited with live virgin female codling moths. Gray elastomer septa were used to dispense communication disruptants around the traps. Dyed male codling moths were released in control and test areas, and the numbers of males captured in control and test traps were compared. In 1991, linear regression curves of percent communication disruption versus logarithm of dose were obtained for three compositions: (E,E)-8,10-dodecadien-1-ol, codlemone (1); codlemone + dodecan-1-ol + tetradecan-1-ol (2); and an equilibrium mixture of the four isomers of 8,10-dodecadien-1-ol (30, (61%EE, 14%ZE, 20%EZ, and 5%ZZ). All three regressions gaver (2) values greater than 0.90. At the 95% confidence limits, slopes and intercepts of compositions 1 and 2 were equivalent, and different from that of composition 3, which produced the greatest percentages of disruption at all doses. In 1992, five treatments were compared at a single dose: 1, 3, none (4), (Z,E)-8,10-dodecadien-1-ol (5), (E,Z)-8,10-dodecadien-1-ol (6). Compositions 5 and 6 gave the greatest and similar percentages of disruption and were different from codlemone (1) and 4 (95% confidence), but not from composition 3. Communication disruption produced by composition 3 was greater than (codlemone), which was greater than 4. PMID- 24241708 TI - Induced resistance in soybean toHelicoverpa zea: Role of plant protein quality. AB - Resistance in soybean toHelicoverpa zea is comprised of both constitutive and inducible factors. In this study, we investigated the induction of resistance byH. zea in both greenhouse and field studies. In a greenhouse experiment, fourth instarH. zea growth rates were reduced by 39% after 24 hr feeding and by 27% after 48 hr when larvae fed on previously wounded V3 foliage (cv. Forrest) compared with undamaged foliage. In a field study, the weight gain by larvae was more than 52% greater when larvae fed for 72 hr on undamaged R2/R3 soybean plants (cv. Braxton) compared to those that fed on previously wounded plants. A significant component of the induced resistance is due to a decline in the nutritional quality of foliar protein following foliar damage byH. zea. Foliar protein was extracted from damaged and undamaged foliage and incorporated into artificial diets. Larval growth was reduced 26% after four days and 49% after seven days on diets containing protein from damaged plants compared to larvae feeding on foliar protein from undamaged plants. Chemical analyses of protein quality also indicated a decline in quality in damaged plants compared to unwounded plants. Increases in lipoxygenase activity (53%), lipid peroxidation products (20%), and trypsin inhibitor content (34%) were observed in protein from wounded plants. Moreover, a 5.9% loss in free amines and 19% loss in total thiols occurred in protein from wounded plants. Larval feeding causes a significant increase in foliar lipoxygenase activity that varied among genotypes. Lipoxygenase isozymes were measured at pH 5.5, pH 7.0, and pH 8.5 in V3 stage plants of Forrest, Hark, D75-1069, and PI 417061 genotypes. Lipoxygenase activity in each genotype was significantly increased after 72 hr of larval feeding at each pH level tested, with the exception of lipoxygenase isozymes at pH 5.5 in genotype PI 417061. Larval feeding on R2/R3 stage plants (field-grown cv. Braxton) for six days also increased foliar lipoxygenase activity. PMID- 24241709 TI - (Z,E,E)-dodecatrien-1-ol: A minor component of trail pheromone of termite,Coptotermes formosanus Shiraki. AB - In the course of the elucidation of the primary structure of an isolated trail pheromone fromC. formosanus, a minor component that had the same molecular weight as the major trail pheromone, (Z,Z,E)-3,6,8-dodecatrien-1-ol [(Z,Z,E)-DTE-OH], was detected in the mass chromatogram ofm/z 180 of capillary GC-MS. The mass spectrum of the minor component showed a prominent pattern of dodecatrien-1-ol. Chemical analysis demonstrated that the complete structure was (Z,E,E)-DTE-OH. Furthermore, capillary GC-MS-HR-SIM analysis indicated that the component existed only in the workers ofCoptotermes formosanus Shiraki and was not present in workers ofReticulitermes speratus (Kolbe). This minor component may be a species specific factor ofC. formosanus, although this was not suggested by a two-choice bioassay. PMID- 24241710 TI - Identification of small molecules that selectively inhibit diacylglycerol lipase alpha activity. AB - Recent genetic evidence suggests that the diacylglycerol lipase (DAGL-alpha) isoform is the major biosynthetic enzyme for the most abundant endocannabinoid, 2 arachidonoyl-glycerol (2-AG), in the central nervous system. Revelation of its essential role in regulating retrograde synaptic plasticity and adult neurogenesis has made it an attractive therapeutic target. Therefore, it has become apparent that selective inhibition of DAGL-alpha enzyme activity with a small molecule could be a strategy for the development of novel therapies for the treatment of disease indications such as depression, anxiety, pain, and cognition. In this report, the authors present the identification of small molecule inhibitor chemotypes of DAGL-alpha, which were selective (>=10-fold) against two other lipases, pancreatic lipase and monoacylglycerol lipase, via high-throughput screening of a diverse compound collection. Seven chemotypes of interest from a list of 185 structural clusters, which included 132 singletons, were initially selected for evaluation and characterization. Selection was based on potency, selectivity, and chemical tractability. One of the chemotypes, the glycine sulfonamide series, was prioritized as an initial lead for further medicinal chemistry optimization. PMID- 24241711 TI - Droplet-based microfluidics: enabling impact on drug discovery. AB - Over the past two decades, the application of microengineered systems in the chemical and biological sciences has transformed the way in which high-throughput experimentation is performed. The ability to fabricate complex microfluidic architectures has allowed scientists to create new experimental formats for processing ultra-small analytical volumes in short periods and with high efficiency. The development of such microfluidic systems has been driven by a range of fundamental features that accompany miniaturization. These include the ability to handle small sample volumes, ultra-low fabrication costs, reduced analysis times, enhanced operational flexibility, facile automation, and the ability to integrate functional components within complex analytical schemes. Herein we discuss the impact of microfluidics in the area of high-throughput screening and drug discovery and highlight some of the most pertinent studies in the recent literature. PMID- 24241712 TI - Overcoming the challenges of drug discovery for neglected tropical diseases: the A.WOL experience. AB - Neglected tropical diseases (NTDs) are a group of 17 diseases that typically affect poor people in tropical countries. Each has been neglected for decades in terms of funding, research, and policy, but the recent grouping of them into one unit, which can be targeted using integrated control measures, together with increased advocacy has helped to place them on the global health agenda. The World Health Organization has set ambitious goals to control or eliminate 10 NTDs by 2020 and launched a roadmap in January 2012 to guide this global plan. The result of the launch meeting, which brought together representatives from the pharmaceutical industry, donors, and politicians, was the London Declaration: a series of commitments to provide more drugs, research, and funds to achieve the 2020 goals. Drug discovery and development for these diseases are extremely challenging, and this article highlights these challenges in the context of the London Declaration, before focusing on an example of a drug discovery and development program for the NTDs onchocerciasis and lymphatic filariasis (the anti-Wolbachia consortium, A.WOL). PMID- 24241713 TI - Socioeconomic inequalities in acute myocardial infarction incidence in migrant groups: has the epidemic arrived? analysis of nation-wide data. AB - OBJECTIVES: We assessed socioeconomic inequalities in relation to acute myocardial infarction (AMI) incidence among major ethnic groups in The Netherlands. METHODS: A nationwide register-based cohort study was conducted (n=2 591 170) between 1 January 1998 and 31 December 2007 among ethnic Dutch and migrant groups from Suriname, Netherlands Antilles, Indonesia, Morocco and Turkey. Standardised household disposable income was used as a proxy for socioeconomic position. Cox proportional hazard models were used to estimate the socioeconomic inequalities in AMI incidence. RESULTS: Among ethnic Dutch, the AMI incidence was higher in the low-income group than in the high-income group: adjusted HRs were 2.05 (95% CI 2.00 to 2.10) for men and 2.33 (95% CI 2.23 to 2.43) for women. Importantly, similar socioeconomic inequalities in AMI incidence were also observed in all minority groups, with the low socioeconomic group having a higher AMI incidence than the high socioeconomic group: adjusted HR ranging from 2.07 (95% CI 1.26 to 3.40) in Moroccans to 2.73 (95% CI 1.55 to 4.80) in Antilleans in men; and from 2.17 (95% CI 1.74 to 2.71) in Indonesians to 3.88 (95% CI 2.36 to 6.38) in Turks in women. CONCLUSIONS: Our findings demonstrate socioeconomic inequalities in AMI incidence in migrant groups and suggest a convergence towards the Dutch general population. If the AMI incidence rates of the low socioeconomic group could be reduced to the level of the high socioeconomic group, this would represent a major public health improvement for all ethnic groups. PMID- 24241714 TI - An echocardiographic abnormality in an HIV patient with coronary disease. PMID- 24241715 TI - 2-Aminopurine optical spectra: Solvent, pentose ring, and DNA helix melting dependence. AB - 2-Aminopurine (2AP) absorption and fluorescence excitation and emission spectra in a series of solvents have been measured to assess effects of solvent polarity. Emission spectra of the free base shift to the red in solvents of a higher dielectric constant, including water but excepting dioxane. Excitation spectra also red-shift, except in water. A change in dipole moment of 2.8 D upon excitation is obtained from a Bilot-Kawski plot which includes data from potentially anomolous solvents such as alcohols but which excludes dioxane and aqueous solvents. Attachment of ribose or 2'-deoxyribose causes 1 to 2-nm shifts in the position of fluorescence excitation and emission spectra of 2AP in water and little change in fluorescence yield. Melting of the DNA duplex d[CTGA(2AP)TTCAG]2 yields a blue shift of the excitation and no shift of the emission spectrum-results consistent with increased exposure to water and formation of 2AP-water H bonds in the ground state. The spectral shift occurs 5 degrees C or more below the helix melting temperature, implying a premelting structural change in the decamer. PMID- 24241716 TI - Fluorimetric metal ion sensing usingN-methyl-9-anthrylhydroxamic acid. AB - We have synthesizedN-methyl-9-anthrylhydroxamic acid, which is a fluorescent analogue ofN-methylbenzohydroxamic acid. Complexation with various di- and trivalent metal ions occurs (logK from 4 to 5) in water with resulting fluorescence quenching. Because the Fe(III) and Al(III) complexes substituted rather slowly, the addition of EDTA provides a temporal method for obtaining some selectivity in the chemosensor. PMID- 24241717 TI - pH-Dependent fluorescence and singlet energy transfer in water-soluble polymers containing eosin and phenol red chromophores. AB - The pH-dependent fluorescence and energy transfer properties of water-soluble polyacrylamide labeled with a donor (eosin) and acceptor (phenol red) were studied. Eosin emission intensity decreases with pH increases. This observation corresponds to the expectation that the fluorescence intensity of eosin should diminish with pH increases resulting from increased spectral overlap between dyes. The lower energy transfer efficiency compared to a pH sensor made with the same polymer, but with a cross-linker, can be explained by the larger distances between the two chromophores resulting from conformational flexibility and electrostatic repulsion of the chromophore ions. PMID- 24241718 TI - Substituent effects on the excited-state properties of platinummeso tetraphenylporphyrins. AB - A study has been undertaken to examine the effect of peripheral substitution on the photophysics of platinum tetraarylporphyrins. The aim of the study was to provide better dyes for oxygen sensing. Substitution of electron rich aryl groups results in red shifts for both the absorption and emission spectra. These observations are explained using simple molecular orbital theory. The lifetime of the excited singlet state for platinum tetraphenylporphyrin is calculated to be shorter than 0.7 psec. The radiative rate constants are on the order of 10(3) sec(-1) while nonradiative rate constants are on the order of 10(4) sec(-1). The model used is sufficiently flexible to be applied to all Pt and Pd porphyrins. PMID- 24241719 TI - Two photon-induced fluorescence intensity and anisotropy decays of diphenylhexatriene in solvents and lipid bilayers. AB - We measured the fluorescence intensity and anisotropy decays of 1,6-diphenyl 1,3,5-hexatriene (DPH)-labeled membranes resulting from simultaneous two-photon excitation of fluorescence. Comparison of these two-photon data with the more usual one-photon measurements revealed that DPH displayed identical intensity decays, anisotropy decays, and order parameters for one- and two-photon excitation. While the anisotropy data are numerically distinct, they can be compared by use of the factor 10/7, which accounts for the two-photon versus one photon photoselection. The increased time 0 anisotropy of DPH can result in increased resolution of complex anisotropy decays. Global analysis of the one- and two-photon data reveals consistency with a single apparent angle between the absorption and the emission oscillators. The global anisotropy analysis also suggests that, except for the photoselection factor, the anisotropy decays are the same for one-and two-photon excitation. This ideal behavior of DPH as a two photon absorber, and its high two-photon cross section, makes DPH a potential probe for confocal two-photon microscopy and other systems where it is advantageous to use long-wavelength (680- to 760-nm) excitation. PMID- 24241721 TI - Dose-response modeling of etoposide-induced DNA damage response. AB - The 2007 National Research Council Report "Toxicity Testing in the 21st Century: A Vision and A Strategy" recommended an integrated, toxicity pathway-oriented approach for chemical testing. As an integral component of the recommendation, computational dose-response modeling of toxicity pathways promises to provide mechanistic interpretation and prediction of adverse cellular outcomes. Among the many toxicity pathways, the DNA damage response is better characterized and thus more suited for computational modeling. In the present study, we formulated a minimal mathematical model of this pathway to examine the dose response for etoposide (ETP), an anticancer drug that causes DNA double strand breaks (DSBs). In the model, DSB results from inhibition of topoisomerase by ETP and p53 is activated by a bistable switch composed of a positive feedback loop between ATM and gammaH2AX. Our stochastic model recapitulated the dose response for several molecular biomarkers measured with flow cytometry in HT1080 cells, including phosphorylated p53, ATM, gammaH2AX, and micronuclei. Model simulations were consistent with a bimodal pattern of p53 activation and a graded population averaged response at high ETP concentrations. The graded response was a result of heterogeneous activation of individual cells due to molecular stochasticity. This work shows the value of combining data collection on single cell responses and mechanistic, stochastic modeling to develop and test hypothesis for the circuitry of important toxicity pathways. Future studies will determine how well this initial modeling effort agrees with a broader set of experimental studies on pathway responses by examining a more diverse group of DNA-damaging compounds. PMID- 24241720 TI - Is 'legal empowerment of the poor' relevant to people with disabilities in developing countries? An empirical and normative review. AB - BACKGROUND: Legal empowerment of the poor is highly relevant to public health as it aims to relieve income poverty, a main determinant of health. The Commission on Legal Empowerment of the Poor (CLEP) has proposed legal empowerment measures in the following four domains: access to justice and the rule of law, property, labor, and business rights. Despite being overrepresented among the poor, CLEP has not explicitly considered the situation of people with disabilities. OBJECTIVES: To examine the empirical evidence for the relevance of the CLEP legal empowerment measures to people with disabilities in low- and lower middle-income countries, and to evaluate the extent to which the Convention on the Rights of Persons with Disabilities (CRPD) addresses those measures. METHODS: Critical literature review of empirical studies and a checklist assessment of the CRPD. RESULTS: Fourteen included articles confirm that people with disabilities experience problems in the domains of access to justice and the rule of law, labor rights, and business rights. No texts on property rights were found. Evidence for the effectiveness of the proposed measures is insufficient. Overall, the CRPD fully or partially supports two-thirds of the proposed measures (seven out of nine measures for access to justice and the rule of law, none of the five measures for property rights, all seven measures for labor rights, and six out of nine measures for business rights). CONCLUSIONS: Although most of the domains of the CLEP legal empowerment measures are relevant to people with disabilities from both empirical and normative perspectives, it is uncertain whether the devised measures are of immediate relevance to them. Further research is warranted in this regard. PMID- 24241722 TI - Photosafety screening of phenothiazine derivatives with combined use of photochemical and cassette-dosing pharmacokinetic data. AB - This study aimed to establish an efficient photosafety screening system, employing in vitro photochemical and cassette-dosing pharmacokinetic (PK) studies. Eight phenothiazine (PTZ) derivatives were selected as model chemicals, and photochemical characterization and cassette-dosing PK study were carried out. In vivo photosafety testing on oral PTZs (100 mg/kg) was also assessed in rats. All the tested PTZs exhibited potent UVA/B absorption with molar extinction coefficients of ca. 3400-4400 M(-1)cm(-1). Under exposure to simulated sunlight (2.0 mW/cm(2)), all PTZs, especially fluphenazine 2HCl (FP) and trifluoperazine 2HCl (TF), tended to generate reactive oxygen species (ROS). Casset-dosing PK studies demonstrated high dermal deposition of FP and TF in rats, and from these findings, taken together with the potent photochemical reactivity, both FP and TF were deduced to be highly phototoxic. In contrast, the phototoxic potential of chlorpromazine HCl (CP) seemed to be low because of moderate ROS generation and limited dermal distribution. Predicted phototoxic risk for PTZs from photochemical and PK data appeared basically to agree with the observed phototoxicity in rats; however, oral CP (100 mg/kg) caused severe phototoxic responses in rats. Metabolites of CP have been recognized to be phototoxic, which might explain in part this false prediction. These findings might also suggest the necessity of complementary testing on drug metabolites for more reliable photosafety evaluation. The combined use of photochemical and PK data might be efficacious for simple and fast prediction of the phototoxic potential of new drug candidates. PMID- 24241723 TI - Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro. AB - In vitro methods for developmental neurotoxicity (DNT) testing have the potential to reduce animal use and increase insight into cellular and molecular mechanisms underlying chemical-induced alterations in the development of functional neuronal networks. Mouse neural progenitor cells (mNPCs) differentiate into nervous system specific cell types and have proven valuable to detect DNT using biochemical and morphological techniques. We therefore investigated a number of functional neuronal parameters in primary mNPCs to explore their applicability for neurophysiological in vitro DNT testing. Immunocytochemistry confirmed that mNPCs express neuronal, glial, and progenitor markers at various differentiation durations (1, 7, 14, and 21 days). Because intracellular calcium ([Ca(2+)]i) plays an essential role in neuronal development and function, we measured stimulus-evoked changes in [Ca(2+)]i at these differentiation durations using the Ca(2+)-responsive dye Fura-2. Increases in [Ca(2+)]i (averages ranging from 65 to 226 nM) were evoked by depolarization, ATP, l-glutamic acid, acetylcholine, and dopamine (up to 87%, 57%, 93%, 28%, and 37% responding cells, respectively) and to a lesser extent by serotonin and gamma-aminobutyric acid (both up to 10% responding cells). Notably, the changes in percentage of responsive cells and their response amplitudes over time indicate changes in the expression and functionality of the respective neurotransmitter receptors and related calcium signaling pathways during in vitro differentiation. The development of functional intercellular signaling pathways was confirmed using multielectrode arrays, demonstrating that mNPCs develop electrical activity within 1-2 weeks of differentiation (55% active wells at 14 days of differentiation; mean spike rate of 1.16 spikes/s/electrode). The combined data demonstrate that mNPCs develop functional neuronal characteristics in vitro, making it a promising model to study chemical-induced effects on the development of neuronal function. PMID- 24241724 TI - Introduction of a nitrogen-fixing cyanobacterium into tobacco shoot regenerates. AB - Tobacco (Nicotiana tabacum L.) shoots associated with the nitrogen-fixing cyanobacterium Anabaena variabilis Kutz. (ATCC 29413) were regenerated in mixed cultures of tobacco callus and the cyanobacterium. The cyanobacteria were localized inside the tissues as well as on the surface of regenerated shoots, formed heterocysts, and were capable of acetylene reduction. PMID- 24241725 TI - The partial purification and characterisation of gibberellin 2beta-hydroxylases from seeds of Pisum sativum. AB - The gibberellin (GA) 2beta-hydroxylases in mature and immature seeds of Pisum sativum have been partially purified and characterised. The enzymes are unstable when stored below pH 7.0 or in the absence of a thiol reagent. The optimum assay pH is between 7.4 and 7.8 and activity is dependent upon the presence of alpha ketoglutarate, Fe(2+) and ascorbate. The 2beta-hydroxylase activities for GA1, GA4, GA9 and GA20 are chromatographically inseparable and correspond to a protein of Mr 44000. The rate of GA 2beta-hydroxylation varies according to substrate and some evidence indicates that the 2beta-hydroxylase activities for GA1 and GA4 and for GA9 and GA20 may reside in different proteins. During pea seed maturation, the specific activity of the enzyme(s) increases dramatically and reaches a maximum at a time when endogenous GA9, GA20, GA29 and GA51 are also at their greatest concentration. This correlation is not the result of substrate induction of enzyme activity. Since the GA 2beta-hydroxylases operate at maximal rate at low substrate concentrations they are incapable of rapidly 2beta-hydroxylating excessive quantities of (exogenously applied) GA1 or GA20. On the basis of the kinetic parameters of the GA 2beta-hydroxylase activities, a generalised model is discussed for the control of the steady-state levels of bioactive hormone under normal physiological conditions. PMID- 24241726 TI - Studies on the growth and development in Spirogyra : VI. Phototropic response of Spirogyra filaments. AB - The phototropic response of Spirogyra sp. filaments and its relation with the different phases of their diurnal movements were studied. The filaments rapidly responded to unilateral irradiation; curvature towards the light source began in their tip region but shifted down to more basal regions. However, this typical and steady phototropic curvature could be observed only in the GnSt phase of the diurnal movement. In the other phases competitive states between the phototropic movement and other kinds of movement were evident. Thus, from the results of our previous and present studies it is proposed that the diurnal movement of Spirogyra filaments is composed of various individual movements, including a phototropic one; among these movements there exists a certain balance determined by the culture conditions and the time of day, and the phototropic movement is relatively inferior to the other movements. PMID- 24241727 TI - Distribution of growth and proton efflux in gravireactive roots of maize (Zea mays L.). AB - Roots of Zea mays were maintained in a vertical orhorizontal position and the local elongation rate and H(+) fluxes were measured using Sephadex beads containing a pH indicator. When the roots were kept horizontally, the growth of the lower side was strongly inhibited and that of the upper side slightly stimulated as compared with vertical roots. The H(+) extrusion, which was greatest in the elongation zone, was strongly inhibited on the lower side and slightly stimulated on the upper side as compared with vertical roots. PMID- 24241728 TI - Copper tolerance in Silene cucubalus : Subcellular distribution of copper and its effects on chloroplasts and plastocyanin synthesis. AB - The uptake, translocation and subcellular distribution of copper as well as its effect on chloroplasts and plastocyanin synthesis were studied in a copper sensitive and a copper-tolerant population of Silene cucubalus (L.) Wib. As a function of time, the copper concentration in roots of tolerant plants increased more slowly than that in roots of sensitive ones. Translocation to the shoot occurred more rapidly in tolerant plants than in sensitive ones. Although it was accumulated in leaf cells, copper was not accumulated in the chloroplasts of either sensitive or tolerant plants. Chlorophyll content was not affected by copper in tolerant plants, whereas sensitive plants became chlorotic. Plastocyanin synthesis was not enhanced as a result of high copper concentrations and no difference in plastocyanin content between tolerant and sensitive plants was detected. Measurements of copper in purified cell walls revealed that storage of the metal in cell-wall material does not play an important role in tolerance mechanism. Uptake characteristics, distribution and cytoplasmic detoxification of copper are discussed. PMID- 24241729 TI - Wall yield threshold and effective turgor in growing bean leaves. AB - The rate of cell enlargement depends on cell-wall extensibility (m) and on the amount of turgor pressure (P) which exceeds the wall yield threshold (Y). The difference (P-Y) is the growth-effective turgor (P e). Values of P, Y and P ehave been measured in growing bean (Phaseolus vulgaris L.) leaves with an isopiestic psychrometer, using the stress-relaxation method to derive Y. When rapid leaf growth is initiated by light, P, Y and P eall decrease. Thereafter, while the growth rate declines in maturing leaves, Y continues to decrease and P eactually increases. These data confirm earlier results indicating that the changes in light-stimulated leaf growth rate are primarily controlled by changes in m, and not by changes in P e. Seedlings incubated at 100% relative humidity have increased P, but this treatment does not increase growth rate. In some cases Y changes in parallel with P, so that P eremains unchanged. These data point out the importance of determining P e, rather than just P, when relating cell turgor to the growth rate. PMID- 24241730 TI - Accumulation of alkaloids in plant vacuoles does not involve an ion-trap mechanism. AB - Alkaloid uptake into vacuoles isolated from a Fumaria capreolata L. cell suspension culture was investigated. The uptake is carrier-mediated as shown by its substrate saturation, its sensitivity to metabolic inhibitors and especially by its exclusive preference for the (S)-forms of reticuline and scoulerine while the (R)-enantiomers which do not occur in this plant species were strictly discriminated. The carrier has a high affinity for (S)-reticuline with a K m=0.3 MUM. The rate of alkaloid uptake was 6 pmol.h(-1).MUl(-1) vacuole, and 0.03 mg alkaloid.mg(-1) vacuolar protein were taken up. Transport was stimulated five-to seven-fold by ATP and was inhibited by the ATPase inhibitors N,N' dicyclohexylcarbodiimide and 4-4'-diisothiocyanatostilbene-2,2' disulfonic acid, as well as by the protonophore carbonyl cyanide m-chlorophenylhydrazone. A number of alkaloids did not compete with labelled (S)-reticuline for uptake into vacuoles. The uptake system is absolutely specific for alkaloids indigenous to the plant from which the vacuoles were isolated. Slight modifications of the topography of an alkaloid molecule even with full retention of its electrical charge results in its exclusion. Alkaloid efflux was also shown to be mediated by a highly specific energy-dependent carrier. These results contradict the previously proposed ion-trap mechanism for alkaloid accumulation in vacuoles. A highly specific carrier-mediated and energy-dependent proton antiport system for alkaloid uptake and release is postulated. PMID- 24241731 TI - The dual location of beta-oxidation enzymes in germinating pea cotyledons. AB - beta-Oxidation enzymes were detected both in the mitochondria and microbodies of pea cotyledons. Intact mitochondria did not show beta-oxidation enzyme activity but in ruptured mitochondria this activity was high. It is apparent that the mitochondrial membrane barrier prevents rapid access of acyl-CoA substrates to matrix beta-oxidation sites. Removal of the membrane barrier permits rapid access of acyl-CoAs and these enzyme activities may then be measured. PMID- 24241732 TI - Carnitine acetyltransferase in pea cotyledon mitochondria. AB - Purified pea cotyledon mitochondria did not oxidise acetyl-CoA in the presence of carnitine. However, acetylcarnitine was oxidised. It was concluded that acetylcarnitine passed through the mitochondrial membrane barrier but acetyl-CoA did not. Only a sensitive radioactive assay detected carnitine acetyltransferase in intact mitochondrion or intact mitoplast preparations. When the mitochondria or mitoplasts were burst, acetyl-CoA substrate was available to the matrix carnitine acetyltransferase and a high activity of the enzyme was measured. The inner mitochondrial membrane is there-fore the membrane barrier to acetyl-CoA but acetylcarnitine is suggested to be transported through this membrane via an integral carnitine: acylcarnitine translocator. Evidence is presented to indicate that when the cotyledons from 48-h-grown peas are oxidising pyruvate, acetylcarnitine formed in the mitochondrial matrix by the action of matrix carnitine acetyltransferase may be transported to extra-mitochondrial sites via the membrane translocator. PMID- 24241733 TI - Potassium channels in Eremosphaera viridis : II. Current- and voltage-clamp experiments. AB - To characterize the assumed potassium channels in the plasma membrane of the green alga Eremosphaera viridis (Kohler et al. 1985), current-voltage (I/V) curves under resting conditions and during an action-potential-like response (CAP) were constructed using voltage- and current-clamp techniques. Under resting conditions the I/V-curves of Eremosphaera showed a distinct upward bending when approaching zero mV, a nearly straight line in the medium part and a downward bending during strong hyperpolarization. Measurements in light and darkness frequently displayed a parallel shift of the I/V-curve in the middle part, indicating a current source which is slowed down by light-off. Using the voltage clamp technique, N-shaped I/V-curves were sometimes observed. The potassium concentration outside influenced the downward-bending part of the I/V-curve whereas the tetraethylammonium cation, known to block potassium channels, reduced the upward-bending part in particular. A change in external pH, either to pH 7 or pH 3.1 from a standard pH 5.5, caused an increase in conductivity. Chemically induced action potentials were released in Eremosphaera under voltage-clamp conditions by light-off and there was both a current flow and an increase in conductivity during the CAP. Clamping the membrane potential at a value more negative than Nernst potential of potassium revealed an inward current, whereas clamping at a more-positive value revealed an outward current. The experiments demonstrate that there is no threshold potential in releasing a CAP. The I/V curves performed under current clamp at the peak of CAP verify a previously found increased conductivity with hyper- or depolarization depending on the external potassium concentration. These experiments provide further evidence that in Eremosphaera potassium channels are involved in the CAP caused by a light-off signal. Additional experiments indicate that after light-off a transient acidification of the cytoplasm takes place in correlation with the CAP and the opening of potassium channels. A preliminary "battery model" is discussed to understand the role of potassium channels during a CAP in pH-regulation of the cytoplasm. PMID- 24241734 TI - Auxin carriers in membranes of lupin hypocotyls. AB - The pH-driven accumulation of [(3)H]indolyl-3-acetic acid (IAA) has been found to occur in membrane vesicles of lupin (Lupinus albus L.) hypocotyls. Most of this association of auxin with membranes is very sensitive to osmotic shock, high concentrations of permeable weak acids, incubation at 20 degrees C for 20 min and to some ionophores. Long incubation times also depress the ability to accumulate radioactive IAA but this ability can be partially restored by a treatment that presumably reconstitutes the pH gradient across the membranes. Two specific inhibitors of auxin transport, N-1-naphtylphthalamic acid and 2,3,5 triiodobenzoic acid, stimulate net IAA uptake with an optimum at about 10(-6) M (pH 5.0). At least two auxin carriers appear to be present in the lupin membrane vesicles. An uptake carrier seems to be saturated at 10(-7) M IAA in the presence of N-1-naphtylphthalamic acid, but higher IAA concentrations are needed to saturate an efflux carrier. The uptake carrier also shows a high affinity for IAA and 2,4-dichlorophenoxyacetic acid and a low affinity for 1-naphthylacetic acid. PMID- 24241735 TI - Compartmentation of glycolysis and of the oxidative pentose-phosphate pathway in Chlamydomonas reinhardii. AB - Glycolytic enzyme activities and enzyme activities of the oxidative pentose phosphate pathway were measured in intact chloroplasts from Chlamydomonas reinhardii. By comparison with the total enzyme activities of intact protoplasts of the alga the data were used to locate these enzymes quantitatively in the algal chloroplast. It was found that the glycolytic chain in C. reinhardii is roughly split into a plastidic and an extraplastidic part. More than 90% of the first part of glycolysis (from fructose-6-phosphate to triose-phosphate is located in the plastid while more than 95% of the second part (from glycerate-3 phosphate to pyruvate) is outside. Around 70% of glucose-6-phosphate dehydrogenase and gluconate-6-phosphate dehydrogenase, two key enzymes of the oxidative pentose phosphate pathway, are located in the plastid. It is concluded that in C. reinhardii the major part of hexose breakdown to triose-phosphate occurs in the chloroplast and that a tight cooperation between the plastid and the cytoplasm is required for appreciable sugar breakdown to occur in the algal cell. PMID- 24241736 TI - Import of glyoxysomal malate dehydrogenase precursor into glyoxysomes: A heterologous in-vitro system. AB - A heterologous in-vitro system is described for the import of the precursor to glyoxysomal malate dehydrogenase from watermelon (Citrullus vulgaris Schrad., cv. Kleckey's Sweet No. 6) cotyledons into glyoxysomes from castor-bean (Ricinus communis L.) endosperm. The 41-kDa precursor is posttranslationally sequestered and correctly processed to the mature 33-kDa subunit by a crude glyoxysomal fraction or by glyoxysomes purified on a sucrose gradient. The import and the cleavage of the extrasequence is not inhibited by metal chelators such as 1,10 phenanthroline and ethylenediaminetetraacetic acid. Uncouplers (carbonylcyanide m chlorophenylhydrazone), ionophores (valinomycin), or inhibitors of oxidative phosphorylation (oligomycin) and ATP-ADP translocation (carboxyatractyloside) do not interfere, thus indicating the independence of the process of import by the organelle from the energization of the glyoxysomal membrane. PMID- 24241737 TI - The induction of contractile roots in Gladiolus grandiflorus. AB - The number of contractile roots formed in gladioli was inversely related to the depth of the planted corm. Below a certain depth, no contractile roots were produced. Large corms did not produce contractile roots at any planting depth but produced two or more small corms. Depth perception is a function of two independent mechanisms, namely, temperature fluctuations in the root-initiation zone and the amount of light perceived mainly by the upper sheath leaf, the length of which varies with planting depth. Various growth substances applied to the leaves or corms did not induce contractile roots in dark-grown plants but roots were induced by indole-3-butyric acid in both small and large corms grown at constant temperatures and light. Abscisic acid retarded the formation of contractile roots under inductive conditions. PMID- 24241738 TI - Plant tyrosine decarboxylase can be strongly inhibited by L-alpha-aminooxy-beta phenylpropionate. AB - Tyrosine decarboxylase (EC 4.1.1.25) from Syringa vulgaris L. cell cultures and from Hordeum vulgare L. seedlings is strongly inhibited by the phenylalanine analogue, L-alpha-aminooxy-beta-phenylpropionate. L-alpha-Aminooxy-beta phenylpropionate is therefore not specific in its inhibitory action against phenylalanine ammonia-lyase (EC 4.3.1.5). Hordeum tyrosine decarboxylase is also very sensitive to alpha-fluoromethyl(3,4-dihydroxyphenyl)alanine, but preparations from Nicotiana tabacum L. and Sanguinaria canadensis L. are largely unaffected by either type of inhibitor. PMID- 24241739 TI - Photooxidative destruction of chloroplasts and its consequences for expression of nuclear genes. AB - Expression of nuclear genes involved in plastidogenesis is known to be controlled by light via phytochrome. Examples are the small subunit (SSU) of ribulose-1,5 bisphosphate carboxylase and the light harvesting chlorophyll a/b binding protein of photosystem II (LHCP). In the present study we show that, beside phytochrome, the integrity of the plastid is essential for the expression of the pertinent nuclear genes as measured at the level of translatable mRNA. When the plastids are severely damaged by photooxidation in virtually carotenoid-free mustard (Sinapis alba L.) seedling cotyledons (made carotenoid-free by the application of Norflurazon, NF), almost no SSU, no SSU precursor, LHCP and LHCP precursor can be detected by immunological assays, and almost no translatable mRNA of SSU and LHCP can be found, although the levels and rates of phytochrome-mediated syntheses of representative cytoplasmic, mitochondrial and glyoxisomal enzymes are not adversely affected and morphogenesis of the mustard seedling proceeds normally (Reibeta et al. 1983; Planta 159, 518-528). Norflurazon per se has no effect on the amount of translatable mRNA of SSU and LHCP as shown by irradiation of NF treated seedlings with far-red light (FR) which strongly activates phytochrome but does not cause photooxidation in the plastids. It is concluded that a signal from the plastid is required to allow the phytochrome-mediated appearance of translatable mRNA for SSU and LHCP. Seedlings not treated with NF show a higher level of translatable mRNALHCP in red light (RL) compared to FR, whereas the mRNASSU levels are the same in RL and FR. These facts indicate that the level of translatable mRNALHCP is adversely affected if the apoprotein is not incorporated into the thylakoid membrane. PMID- 24241740 TI - Properties of alpha-galactosidase II(2) from Vicia faba seeds. AB - alpha-Galactosidase II(2) (MW ~ 43 390) from resting Vicia faba L. seeds had been shown to possess D-glucose/D-mannose-specific lectin activity. Inhibition studies with monosaccharides and an examination of the effects of heat and pH on the catalytic and lectin activities of the enzyme indicate that the enzyme substrate and the lectin haptens bind at different sites on the protein. D-Mannosebinding has been investigated by equilibrium dialysis and spectrophotometrically. Both methods yield Ka values of approx. 3.10(3) M(-1) for the interaction and there would appear to be two mannosebinding sites per molecule of enzyme protein. The lectin properties of V. faba alpha-galactosidase II(2) have been discussed in relation to both V. faba lectin (favin) and other legume alpha-galactosidases. PMID- 24241741 TI - Enzymes of serine and glycine metabolism in leaves and non-photosynthetic tissues of Pisum sativum L. AB - A comparative study is presented of the activities of enzymes of glycine and serine metabolism in leaves, germinated cotyledons and root apices of pea (Pisum sativum L.). Data are given for aminotransferase activities with glyoxylate, hydroxypyruvate and pyruvate, for enzymes associated with serine synthesis from 3 phosphoglycerate and for glycine decarboxylase and serine hydroxymethyltransferase. Aminotransferase activities differ between the tissues in that, firstly, appreciable transamination of serine, hydroxypyruvate and asparagine occurs only in leaf extracts and, secondly, glyoxylate is transaminated more actively than pyruvate in leaf extracts, whereas the converse is true of extracts of cotyledons and root apices. Alanine is the most active amino-group donor to both glyoxylate and hydroxypyruvate. 3-Phosphoglycerate dehydrogenase and glutamate: O-phosphohydroxypyruvate aminotransferase have comparable activities in all three tissues, except germinated cotyledons, in which the aminotransferase appears to be undetectable. Glycollate oxidase is virtually undetectable in the non-photosynthetic tissues and in these tissues the activity of glycerate dehydrogenase is much lower than that of 3-phosphoglycerate dehydrogenase. Glycine decarboxylase activity in leaves, measured in the presence of oxaloacetate, is equal to about 30-40% of the measured rate of CO2 fixation and is therefore adequate to account for the expected rate of photorespiration. The activity of glycine decarboxylase in the non-photosynthetic tissues is calculated to be about 2-5% of the activity in leaves and has the characteristics of a pyridoxal-and tetrahydrofolate-dependent mitochondrial reaction; it is stimulated by oxaloacetate, although not by ADP. In leaves, the measured activity of serine hydroxymethyltransferase is somewhat lower than that of glycine decarboxylase, whereas in root apices it is substantially higher. Differential centrifugation of extracts of root apices suggests that an appreciable proportion of serine hydroxymethyltransferase activity is associated with the plastids. PMID- 24241742 TI - Incubation of corn coleoptiles with auxin enhances in-vitro fusicoccin binding. AB - Binding of fusicoccin (FC) to microsomal preparations of corn (Zea mays L.) coleoptiles is enhanced after incubation of the tissue with indole-3-acetic acid (IAA). Treatment of the kinetic data according to Scatchard shows that the enhancement is a consequence of an increase in the number of high-affinity FC binding sites without changes of their KD. The minimal effective concentration of IAA is 10(-7) M; above 10(-5) M the effect declines. The stimulation is insensitive to protein-synthesis inhibitors (cycloheximide and puromycin). The same effect is observed with the synthetic auxins 2,4-dichlorophenoxyacetic acid and naphtalene-1-acetic acid while it is abolished by the auxin antagonists naphtalene-2-acetic acid and p-chlorophenoxyisobutyric acid. Since the above effect is only observed with intact tissue and not after incubation of IAA with microsomal preparations, a direct interaction of IAA with the FC-binding sites is ruled out and an alternative mechanism must be sought. PMID- 24241743 TI - The origin of photosystem-I-mediated electron transport stimulation in heat stressed chloroplasts. AB - Exposure of isolated chloroplasts of pea (Pisum sativum L.) to temperatures above 35 degrees C leads to a stimulation of photosystem-I-mediated electron transport from dichlorophenolindophenol to methyl viologen. The threshold temperature for this stimulation coincides closely with that for heat-induced inhibition of photosystem-II activity in such chloroplasts. This coincidence is explained in terms of a rearrangement of the thylakoid membrane resulting in the exposure of a new set of donor sites for dichlorophenolindophenol within the cytochrome f/b 6 complex of the electron-transport chain linking the two photosystems. PMID- 24241744 TI - Alkaline inorganic pyrophosphatase and starch synthesis in amyloplasts. AB - The aim of this work was to see if amyloplasts contained inorganic pyrophosphatase. Alkaline pyrophosphatase activity, largely dependant upon MgCl2 but not affected by 100 MUM ammonium molybdate or 60-100 mM KCl, was demonstrated in exracts of developing and mature clubs of the spadix of Arum maculatum L. and of suspension cultures of Glycine max L., but not in extracts of the developing bulb of Allium cepa L. The maximum catalytic activity of alkaline pyrophosphatase in the above tissues showed a positive correlation with starch synthesis, and in the first two tissues was shown to exceed the activity of ADPglucose pyrophosphorylase. Of the alkaline pyrophosphatase activity in lysates of protoplasts of suspension cultures of Glycine max, 57% was latent. Density gradient centrifugation of these lysates showed a close correlation between the distribution of alkaline pyrophosphatase and the plastid marker, nitrite reductase. It is suggested that much, if not all, of the alkaline pyrophosphatase in suspension cultures of Glycine max is located in the plastids. PMID- 24241746 TI - Erratum. PMID- 24241745 TI - Leaf senescence in a non-yellowing mutant of Festuca pratensis: Photosynthesis and photosynthetic electron transport. AB - The photosynthetic capacity of detached leaves of a non-yellowing mutant of Festuca pratensis Huds. declined during senescence at a similar rate to that in a normal cultivar. Respiratory oxygen uptake in the dark continued at similar rates in both genotypes during several days of senescence. In chloroplasts isolated from leaves at intervals after excision, the rate of photosystem I (PS I) mediated methyl viologen reduction using reduced N,N,N',N'-tetramethyl-p phenylene diamine as electron donor also declined in both genotypes, possibly due to loss of integrity of the photosynthetic apparatus in the cytochrome f plastocyanin region. There was a similar fall in PS II electron transport using water as electron donor and measured at the rate of reduction of 2,6 dichlorophenolindophenol. Partial restoration of this activity by the addition of diphenyl carbazide was evidence for lability of the oxygen-evolving complex during senescence. An accentuated difference between mutant and normal material in this case indicated that the mutant retains a greater number of functional PS II centres. Changes in the light-saturation characteristics of the two photosystems have been discussed in relation to the organization of the photosynthetic membranes during senescence. PMID- 24241748 TI - Inactivation of medial prefrontal cortex or acute stress impairs odor span in rats. AB - The capacity of working memory is limited and is altered in brain disorders including schizophrenia. In rodent working memory tasks, capacity is typically not measured (at least not explicitly). One task that does measure working memory capacity is the odor span task (OST) developed by Dudchenko and colleagues. In separate experiments, the effects of medial prefrontal cortex (mPFC) inactivation or acute stress on the OST were assessed in rats. Inactivation of the mPFC profoundly impaired odor span without affecting olfactory sensitivity. Acute stress also significantly reduced odor span. These findings support a potential role of the OST in developing novel therapeutics for disorders characterized by impaired working memory capacity. PMID- 24241749 TI - Deletion of PTEN produces deficits in conditioned fear and increases fragile X mental retardation protein. AB - The phosphatase and tensin homolog detected on chromosome 10 (PTEN) gene product modulates activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The PI3K pathway has been found to be involved in the regulation of the fragile X mental retardation protein, which is important for long-term depression and in the formation of new memories. We used delayed fear conditioning and trace fear conditioning to determine learning and memory deficits in neuron subset-specific Pten (NS-Pten) conditional knockout (KO) mice. We found that NS-Pten KO mice had deficits in contextual learning and trace conditioning, but did not have deficits in the ability to learn a conditioned stimulus. Furthermore, we found increased levels in the total and phosphorylated forms of the fragile X mental retardation protein (FMRP) in the hippocampus of NS-Pten KO mice. PMID- 24241751 TI - Fracture surfaces of granular pastes. AB - Granular pastes are dense dispersions of non-colloidal grains in a simple or a complex fluid. Typical examples are the coating, gluing or sealing mortars used in building applications. We study the cohesive rupture of thick mortar layers in a simple pulling test where the paste is initially confined between two flat surfaces. After hardening, the morphology of the fracture surfaces was investigated, using either the box counting method to analyze fracture profiles perpendicular to the mean fracture plane, or the slit-island method to analyze the islands obtained by cutting the fracture surfaces at different heights, parallel to the mean fracture plane. The fracture surfaces were shown to exhibit scaling properties over several decades. However, contrary to what has been observed in the brittle or ductile fracture of solid materials, the islands were shown to be mass fractals. This was related to the extensive plastic flow involved in the fracture process. PMID- 24241750 TI - Learned together, extinguished apart: reducing fear to complex stimuli. AB - Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuates fear responding and prevents the return of fear in pure tone Pavlovian fear conditioning. Here we sought to examine whether this effect also applies to a more complex fear memory. First, we show that after fear conditioning to the simultaneous presentation of a tone and a light (T+L) coterminating with a shock, the compound memory that ensues is more resistant to fear extinction than simple tone-shock pairings. Next, we demonstrate that the compound memory can be disrupted by interrupting the reconsolidation of the two individual components using a sequential retrieval+extinction paradigm, provided the stronger compound component is retrieved first. These findings provide insight into how compound memories are encoded, and could have important implications for PTSD treatment. PMID- 24241752 TI - Transient gene expression in tobacco protoplasts: I. Time course of CAT appearance. AB - The early events of transient gene expression have been investigated monitoring CAT activity in tobacco protoplasts encoded by the recombinant plasmid pRT101cat. The first appearance of CAT activity was observed within 30 minutes after the outset of cultivation, and maximal values were obtained between four and 24 hours. CAT expression, at the level of RNA synthesis, could not be inhibited by cordycepin (3'deoxyadenine) added one hour after protoplast plating, whereas cycloheximide, an inhibitor of protein synthesis, showed an influence during the first four hours. This indicates a rapid decay of biologically active forms of both the DNA transferred and the CAT-mRNA synthesized within the first hours. These results suggest that in the tobacco protoplast system CAT protein stability lasts up to two weeks rather than a continuous synthesis of new enzyme. PMID- 24241753 TI - Transient gene expression in tobacco protoplasts: II. Comparison of the reporter gene systems for CAT, NPT II, and GUS. AB - The reporter genes for Chloramphenicolacetyltransferase (CAT), Neomycinphosphotransferase-(NPT)-II and beta-Glucuronidase (GUS) were compared in transient gene expression experiments in tobacco mesophyll protoplasts. For this purpose, nearly identical chimeric genes controlled by the CaMV 35 S promoter were constructed. The detection level of each system was determined yielding the following order of relative sensitivity: CAT English River system > Winnipeg River system > control sites. In the Wabigoon River system the bioavailability of mercury increases with distance downstream of the historical point source. Mercury concentrations in the biota studied were highly correlated with mercury concentrations in fish species which are of sport and commercial interest. The locations where young fish obtain their bodyburdens are known typically within 100 m. The biota studied compare favourably with the criteria proposed by Phillips (1980) as prerequisites for biological indicators. The wide distribution of young pike, perch and crayfish in North America, Europe and Asia may enhance their appeal as biomonitors. PMID- 24241776 TI - Environmental impact of seawater desalination plants. AB - Enormous amounts of seawater are desalted everyday worldwide. The total world production of fresh water from the sea is about 2621 mgd (9.92 million m(3) day( 1) 1985 figures). Desalting processes are normally associated with the rejection of high concentration waste brine from the plant itself or from the pretreatment units as well as during the cleaning period. In thermal processes, mainly multistage flash (MSF) thermal pollution occurs. These pollutants increase the seawater temperature, salinity, water current and turbidity. They also harm the marine environment, causing fish to migrate while enhancing the presence of algae, nematods and tiny molluscus. Sometimes micro-elements and toxic materials appear in the discharged brine.This paper will discuss the impact of the effluents from the desalination plants on the seawater environment with particular reference to the Saudi desalination plants, since they account for about 50% of the world desalination capacity. PMID- 24241777 TI - Turbidity and seawater intrusion in Laguna de Bay. AB - The ecological role of seawater intrusion in Laguna de Bay is assessed due to the operation of the Napindan Hydraulic Control Structure (NHCS). Turbidity is recognized as one limiting factor in the lake's biological productivity. Hence, to stop the natural backflow of seawater to Laguna de Bay removes one important contributory factor in facilitating an early water clearing of Laguna de Bay for a higher annual biological productivity. PMID- 24241778 TI - The treatment model of the guidance center for gamblers and their relatives in Vienna/Austria. AB - Within 8 years, "Gamblers Anonymous" in Vienna evolved into a guidance center for gamblers and their relatives, with professional aid. It is a non-profit institution and the therapeutic team consists of one psychologist, one social worker and one psychiatrist. The clients can remain anonymous, but about 90% of them reveal their identity. The treatment model integrating professional therapy and self-help is presented. The reasons we decided to base our work on an "addiction model" of pathological gambling are explained. All the clients consulting our center in 1990 (N=237) are described according to age, sex, types of gambling, duration of problem gambling, family status, profession, income, debts, and income/debt relationship. Finally, the treatment program of our center is presented. PMID- 24241779 TI - Therapy with male pathological gamblers: Between self help group and group therapy-Report of a developmental process. AB - A therapy project was developed for pathological gambling patients and, within a three year period, more than 60 gamblers were studied and treated. Diagnostic evaluation was made according to DSM-III. In addition to individual and family therapy, we designed a voluntary group setting. In this report, we concentrate first on the development of group work, then on some psychodynamic hypotheses about the personality of the gambler. We also try to show the correspondence between these hypotheses and the group process. Pathological gambling is seen as an attempt at self-healing and a strategy of conflict-solving; the slot machine, as an inanimate object, offers a temporary symbiosis with clear limitations; the gambling will come to a guaranteed end, either when all of the money is lost, or when gaming ends at night. Finally, we list some recommendations for the treatment of gamblers in group therapy. PMID- 24241780 TI - Diagnosis and therapy of male gamblers in a university psychiatric hospital. AB - From 1980 to mid-1990 fifty-one gamblers were evaluated and treated at the psychiatric university hospital of Homburg/Saar in Germany. All were men with a mean age of 33.7 years. Gambling had lasted 5.2 years on average. Most patients were motivated to undergo therapy by members of their family. The majority of them had been in psychotherapeutic treatment before. Thirty-six of the 51 patients had committed punishable acts including fraud and embezzlement and, in 7 cases, robbery. The sample could be divided into three clinical subgroups. The first group consisted of patients with severe psychiatric diseases such as schizophrenia, manic-depressive illness or organic brain disorder. Patients of the second group suffered from serious personality disorders. Those of the third group showed deep-rooted problems in their current relationships. PMID- 24241781 TI - Gambling in revolutionary Paris - The Palais Royal: 1789-1838. AB - By the revolution of 1789, the four-story, quadrangular Palais Royal in Paris had become the most glittering tourist center of Europe, with 180 shops and cafes in its ground floor arcades. By 1791, its basement and secondary story contained over 100 separate, illicit gambling operations featuring the most popular dice and card games. The mania for gambling had been transferred from defunct, monarchical Versailles to the thriving, bourgeois Palais Royal, where the five main gaming clubs throbbed from noon till midnight. During the Revolution, Prince Talleyrand won 30,000 francs at one club, and after Waterloo in 1815, Marshal Blucher lost 1,500,000 francs in one night at another. To bring the situation under control and raise taxes for the state, in 1806 Napoleon legalized the main clubs, which from 1819 to 1837 grossed an enormous 137 million francs. When the anti-gambling forces triumphed in 1837 and the clubs were closed down, the National Guard had to be called out to evict the mobs of gamblers who refused to leave the tables. Dramatic reports from Revolutionary police raids, and quotations from the memoirs of humorous French gamblers and shocked foreign visitors, provide anecdotal illustrations of the 49 years during which the Palais Royal was the most intriguing and picturesque gambling mecca of Europe-and probably of the world. PMID- 24241782 TI - A survey of fruit machine gambling in adolescents. AB - Fruit machine gambling among children and young people in the United Kingdom has attracted increasing interest. Since 1985 a number of questionnaire surveys have been conducted attempting to assess the incidence of adolescent fruit machine use and to explore its relationship with delinquency. Data yielded by these surveys have been somewhat inconsistent. Estimates of the prevalence of fruit machine gambling have varied considerably and there is disagreement over its association with deviant behaviour. Researchers have drawn divergent conclusions with different implications for legislation. In the present study, questionnaires were administered to 1,395 11-12 year old and 14-15 year old school children in the Birmingham area. Although for the majority, fruit machine gambling was found to be an infrequent activity involving fairly small amounts of money, a small but significant proportion were found to be gambling often and spending in excess of their income. There was also evidence to suggest that arcades may serve as venues for undesirable activities. PMID- 24241783 TI - Perceptions by treatment staff of critical tasks in the treatment of the compulsive gambler. AB - Seventy-five clinicians who treat compulsive gamblers were surveyed. Each rated 89 clinical tasks and responsibilities for importance in the treatment of this population. Analysis of those items for which a plurality of clinicians rated the item as critical was chosen as the criteria of importance. A principal components analysis was conducted to determine the underlying structure of clinical perceptions of importance. An eight-dimensional model was found to describe perceptions in the most satisfactory way. The analysis revealed five major and three minor clusters of tasks and responsibilities. The major dimensions were labeled as (1) self-help/social support, (2) crisis interventions, (3) behavioral resources for change, (4) psychodynamics of treatment, and (5) crisis severity. The minor dimensions were (6) knowledge and training, (7) ethics and sensitivity to needs, and (8) confidentiality and regulations. A brief discussion of the implications are presented. PMID- 24241784 TI - Predicting outcomes: Sports and stocks. AB - Many gamblers and most fans, players, and coaches offer causal explanations for long runs of good or bad performance in sports and financial analysts are quick to offer explanations for the daily performance of the stock market. The records of professional basketball and baseball teams and the Dow Jones daily closing average for a ten year period were evaluated for trends (streaks). The records of teams were also evaluated to assess whether the record against opponents, the home court or home field advantage, and-for baseball teams-the record of the winning and losing pitcher (excluding the current game) predicted the outcome of individual games. Recent performance is, at best, a very weak predictor of current performance and the three best predictors for baseball (pitching, home field, and record against opponent) together accounted for only 1.7% of the variance in the outcomes of individual games. We overestimate our ability to predict. This overconfidence is likely to play a role in maintaining gambling behaviors. PMID- 24241785 TI - Community-level adult daily smoking prevalence moderates the association between adolescents' cigarette smoking and perceived smoking by friends. AB - Few studies have investigated the complex interactions among the individual- and community-level social risk factors that underlie adolescents' smoking behaviors. This study investigated whether community-level adult daily smoking prevalence is associated with adolescents' smoking and whether it moderates the associations between perceived friends' smoking approval and smoking behavior and adolescents' own smoking. Self-reported data from 1,190 youths (50.3% female; 13-18 years old) in 50 midsized Californian cities were obtained through telephone interviews. Community characteristics were obtained from 2010 GeoLytics data. Community adult daily smoking prevalence was ascertained from telephone interviews with 8,918 adults conducted in the same 50 cities. Multilevel analyses, controlling for individual and city characteristics, were used to predict adolescents' past 12 month smoking from perceived friends' smoking approval and smoking behavior and from community adult daily smoking prevalence. Results showed that perceived friends' smoking approval and behavior were associated positively with adolescents' smoking, as was the community-level prevalence of adult daily smoking. Furthermore, the association between perceived friends' smoking behavior and adolescents' own smoking was moderated by the prevalence of adult daily smokers in the community. Specifically, the association was stronger in cities with higher prevalence of adult smokers. These results suggest that adult community norms that are more supportive of smoking may enhance the influence of friends' smoking behavior. Therefore, interventions designed to prevent or reduce youths' smoking should also focus on reducing smoking by adults. PMID- 24241786 TI - The stressful (and not so stressful) nature of language brokering: identifying when brokering functions as a cultural stressor for Latino immigrant children in early adolescence. AB - Language brokering remains prevalent among immigrant families, but it is widely assumed that brokering functions as a cultural stressor, resulting in adverse health outcomes for immigrant youth. Few studies, however, have tested this assumption, particularly while using longitudinal data and capturing multiple dimensions of brokering. Thus, this study examined how depressive symptoms and family-based acculturation stress mediated the relationships between various aspects of brokering (i.e., frequency of brokering, positive and negative feelings about brokering, brokering norms, and brokering efficacy) and alcohol, cigarette, and marijuana use and other risky behaviors. Using longitudinal survey data from 234 Latino early adolescents in 6th-8th grades (M age = 12.4 years; Females = 46.2 %), brokering for parents indirectly affected alcohol and marijuana use through family-based acculturation stress; however, these significant indirect effects became non-significant when taking into account negative brokering feelings and brokering as a burden on one's time. Feeling positively or efficacious about brokering or having pro-brokering norms did not directly predict any adverse mental and behavioral health outcomes. Moderation analyses, however, revealed that brokering for parents did not seem to function as a stressor when Latino early adolescents were high in brokering efficacy (e.g., feeling confident in one's ability to broker) or descriptive brokering norms (e.g., perceiving one's peers as brokering often). By contrast, when Latino early adolescents perceived brokering as a burden, brokering for parents functioned as a stressor, placing Latino early adolescents at risk for family based acculturation stress, and in turn, alcohol and marijuana use. Such findings point to the complexity of brokering. PMID- 24241787 TI - Circulating hormones and breast cancer risk in premenopausal women: a randomized trial of low-dose tamoxifen and fenretinide. AB - Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG <= 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events. PMID- 24241788 TI - Impact of age at first childbirth on glucose tolerance status in postmenopausal women: the 2008-2011 Korean National Health and Nutrition Examination Survey. AB - OBJECTIVE: The objective of the current study was to determine whether there was an association between age at first childbirth and glucose tolerance status in postmenopausal women. RESEARCH DESIGN AND METHODS: This study was based on the data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare from 2008-2011. Of 37,753 participants, data for 4,965 postmenopausal women were included in the analysis. Subjects were subdivided according to the age at first childbirth as follows: <=19, 20-24, 25-29, and >=30 years. Multivariate logistic regression analyses were used to identify whether there was an independent association between age at first childbirth and glucose tolerance status by adjusting for potential confounding factors. RESULTS: The prevalence of impaired fasting glucose (IFG) and diabetes was 21.8% (1.066 of 4.965) and 15.3% (774 of 4,965), respectively. Diabetes prevalence differed significantly between the subgroups and was higher with earlier age at first childbirth: it was 10.9% in subjects aged >=30 years and 23.8% in subjects aged <=19 years at first childbirth. After fully adjusting for potential confounding factors, including lifestyle, sociodemographic factors, known diabetes risk factors, and reproductive factors, age at first childbirth <=19 years was significantly associated with diabetes (odds ratio 1.492 [95% CI 1.005-2.215]). No significant associations were found between age at first childbirth and IFG. CONCLUSIONS: Age at first childbirth influenced diabetes risk in postmenopausal women, and adolescent pregnancy was independently associated with a higher risk of diabetes in postmenopausal women. PMID- 24241790 TI - Glucagon response to oral glucose challenge in type 1 diabetes: lack of impact of euglycemia. AB - OBJECTIVE Previous studies have demonstrated aberrant glucagon physiology in the setting of type 1 diabetes (T1D) but have not addressed the potential impact of ambient glycemia on this glucagon response. Thus, our objective was to evaluate the impact of euglycemia versus hyperglycemia on the glucagon response to an oral glucose challenge in T1D. RESEARCH DESIGN AND METHODS Ten adults with T1D (mean age 56.6 +/- 9.0 years, duration of diabetes 26.4 +/- 7.5 years, HbA1c 7.5% +/- 0.77, and BMI 24.1 kg/m(2) [22.6-25.4]) underwent 3-h 50-g oral glucose tolerance tests (OGTTs) on two separate days at least 24 h apart in random order under conditions of pretest euglycemia (plasma glucose [PG] between 4 and 6 mmol/L) and hyperglycemia (PG between 9 and 11 mmol/L), respectively. RESULTS Glycemic excursion on the OGTT was similar between the euglycemic and hyperglycemic tests (P = 0.72 for interaction between time postchallenge and glycemic setting). Interestingly, glucagon levels increased in response to the OGTT under both glycemic conditions (P < 0.001) and there were no differences in glucagon response between the euglycemic and hyperglycemic days (P = 0.40 for interaction between time postchallenge and glycemic setting). In addition, the incretin responses to the OGTT (glucose-dependent insulinotropic polypeptide, glucagon like peptide-1, glucagon-like peptide-2) were also not different between the euglycemic and hyperglycemic settings. CONCLUSIONS In patients with T1D, there is a paradoxical increase in glucagon in response to oral glucose that is not reversed when euglycemia is achieved prior to the test. This abnormal glucagon response likely contributes to the postprandial hyperglycemia in T1D irrespective of ambient glycemia. PMID- 24241789 TI - Hyperglycemia has a greater impact on left ventricle function in South Asians than in Europeans. AB - OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58-86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide beta +/- SE 0.09 +/- 0.04, P = 0.01, vs. -0.04 +/- 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e' 0.69 +/- 0.12, P < 0.0001, vs. 0.09 +/- 0.2, P = 0.6, P for interaction 0.005), and systolic function (s' -0.11 +/- 0.06, P = 0.04, vs. 0.14 +/- 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction. PMID- 24241791 TI - Alcohol withdrawal is associated with a downregulation of large-conductance Ca2+ activated K+ channels in rat inferior colliculus neurons. AB - RATIONALE: Large conductance calcium-activated potassium (BK(Ca) or K(Ca)1.1) channels are well-known molecular targets for the action of alcohol and therefore may play an important role in the pathogenesis of alcohol withdrawal syndrome. OBJECTIVES: We evaluate the modifications of total outward K+ currents and protein expression of BK(Ca) channels alpha-subunit in inferior colliculus (IC) neurons obtained from controls and rats subjected to alcohol withdrawal associated with enhanced susceptibility to seizures. METHODS: Outward K+ currents and BK(Ca) channel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively. RESULTS: Total outward K+ current density was significantly reduced in IC neurons at 24 and 48 h during the alcohol withdrawal period when the susceptibility to seizures was maximal and absent, respectively. The iberiotoxin-sensitive (BK(Ca)) current density and conductance also were significantly reduced at 24 h following alcohol withdrawal. Consistent with functional data, the levels of protein expression of alpha-subunit associated with BK(Ca) channels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal. CONCLUSIONS: The downregulation of BK(Ca) channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BK(Ca) channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures. PMID- 24241793 TI - A transient duplication of the acetolactate synthase gene in a cell culture of Datura innoxia. AB - A 2.0 kb fragment of the yeast ILV2 gene, which codes for the target enzyme acetolactate synthase (ALS) of the herbicide chlorsulfuron, was shown to hybridize to the nuclear DNA of a haploid cell culture of Datura innoxia P. Mill. Nuclear DNA of a chlorsulfuron resistant line of D. innoxia, CSR6, gave a prominent 2.65 kb band when cleaved by either EcoRI or HindIII. The 2.65 kb band has been shown to hybridize with the yeast ILV2 probe. A herbicide resistant line descended from CSR6 by continuous culture resulted in the loss of the 2.65 kb restriction fragment. These observations suggest that CSR6 resulted from a large tandem duplication of the ALS gene and that a point mutation for herbicide resistance in an ALS gene repeat unit of the duplication was selected during subsequent growth of the resistant line. PMID- 24241794 TI - Transfer of the 1BL/1RS wheat-rye-translocation from hexaploid bread wheat to tetraploid durum wheat. AB - The present study describes a cytological stable alien chromosome translocation in tetraploid durum wheat. By crossing the hexaploid 1BL/1RS wheat-rye translocation line "Veery" to the tetraploid durum wheat cultivar "Cando" it was possible to select a 28 chromosomic strain homozygous for the 1BL/1RS translocation. The disease resistance potential of the short arm of rye chromosome 1R, which has been widely introduced in many hexaploid bread wheat cultivars could be now also used for the improvement of durum wheat. PMID- 24241795 TI - Screening salt-tolerant barley genotypes via F1 anther culture in salt stress media. AB - Anthers of two six-row barley cultivars Diamond (a germination salt sensitive cultivar) and Men Yuan Liang Lan (a germination salt tolerant cultivar), and their F1 reciprocal crosses were cultured in liquid media containing 0, 0.4, 0.6, and 0.8% Na2SO4. A total of 138 green pollen plants were obtained: 7 from Na2SO4 media, 128 from Na2SO4 free medium. Seeds of two successive generations of 61 pollen plants were germinated in a series of Na2SO4 solution (0 to 5.5%). It was found that among 37 progenies from F1 pollen in Na2SO4 free medium, 11 were as sensitive as "Diamond", 12 were intermediate to the two parents, 7 were equal to the salt tolerant parent and 7 were more tolerant to Na2SO4 than 'Men Yuan Liang Lan'. Whereas, no progeny from F1 pollen in high salt media was as susceptible as the susceptible parent; 2 were intermediate, 2 were equal to the salt tolerant parent and 2 were more tolerant than the salt tolerant parent. The results indicate that culturing anthers in Na2SO4 media effectively eliminated salt susceptible progenies. All 16 microspore-derived lines of Diamond were as susceptible as 'Diamond' to Na2SO4. The 5 lines from 'Men Yuan Liang Lan' microspores were as resistant to Na2SO4 as 'Men Yuan Liang Lan'. All of the lines breed-true. The results indicate that the lines exhibiting elevated levels of tolerance to salt probably resulted from recombination of genes rather than from spontaneous mutation. PMID- 24241792 TI - Protein-protein interaction network analysis in chronic obstructive pulmonary disease. AB - BACKGROUND: The aim of this study was to investigate the gene expression profile of chronic obstructive pulmonary disease (COPD) patients and non-COPD patients. METHODS: Microarray raw data (GSE29133) was downloaded from Gene Expression Omnibus, including three COPD samples and three normal controls. Gene expression profiling was performed using Affymetrix human genome u133 plus 2.0 GeneChip. Differentially expressed genes were identified by Student's t test and genes with p < 0.05 were considered significantly changed. Up- and downregulated genes were submitted to the molecular signatures database (MSigDB) to search for a possible association with other previously published gene expression signatures. Furthermore, we constructed a COPD protein-protein interaction (PPI) network and used the connectivity map (cMap) to query for potential drugs for COPD. RESULTS: A total of 680 upregulated genes and 530 downregulated genes in COPD were identified. The MSigDB investigation found that upregulated genes were highly similar to gene signatures that respond to interferon and downregulated genes were similar to erythroid progenitor cells from fetal livers of E13.5 embryos with KLF1 knocked out. A PPI network consisting of 814 gene/proteins and 2,613 interactions was identified by Search Tool for the Retrieval of Interacting Genes. The cMap predicted helveticoside, disulfiram, and lanatoside C as the top three possible drugs that could perhaps treat COPD. CONCLUSION: Comprehensive analysis of the gene expression profile for COPD versus control reveals helveticoside, disulfiram, and lanatoside C as potential molecular targets in COPD. This evidence provides a new breakthrough in the medical treatment of patients with COPD. PMID- 24241796 TI - The effect of Ph gene alleles on synaptonemal complex formation in Triticum aestivum * T. kotschyi hybrids. AB - Chromosome pairing at zygotene-pachytene was studied in Triticum aestivum * T. kotschyi hybrids (2n=5x=35, genomic constitution ABDC(U)S(v)) by electron microscopy of synaptonemal complexes in spread microsporocyte nuclei. Hybrids carrying either the Ph allele or the ph allele, which differ markedly in metaphase I pairing, are both capable of greater than 90% pachytene pairing, although pairing in the Ph hybrids appeared slower or less synchronised. In both genotypes branched synaptonemal complexes were formed by intra-and interchromosomal pairing. The Ph gene control on homoeologous pairing does not act on the ability to pair into synaptonemal complexes. It may act on the rate of pairing or the time of crossing over. PMID- 24241797 TI - The effect of the 4B chromosomes of hexaploid wheat on the growth and regeneration of callus cultures. AB - Calli were initiated from immature embryos of nine lines of hexaploid wheat (Triticum aestivum L. em. Thell). These were the euploid lines Chinese Spring and Cappelle-Desprez, a line of Chinese Spring ditelocentric for the long arm of 4B, four substitution lines of Chinese Spring in which chromosome 4B has been replaced by its homologues from different wheat varieties and substituted into Chinese Spring and a substitution line of Besostaya I 4B into Cappelle-Desprez. The calli from these lines were found to differ in their growth rates and morphogenic and regenerative activities. The substitution of different 4B chromosomes into Chinese Spring significantly increased morphogenesis and shoot regeneration from callus. The potential for developing wheat lines with improved culture characteristics is discussed. PMID- 24241798 TI - X-ray irradiation promoted asymmetric somatic hybridisation and molecular analysis of the products. AB - Complementation of two metabolic deficiences - nitrate reductase and tryptophan synthase - was used to select for somatic fusion hybrids between tobacco (Nicotiana tabacum) and henbane (Hyoscyamus muticus) with prior X-irradiation of one partner. Using species specific, radioactively labelled DNA probes it could be shown that a) irradiation significantly reduced the amount of chromosomal DNA of the irradiated fusion partner in the somatic hybrid, b) irradiation with doses which completely inhibit protoplast division did not pevent transfer of substantial amounts of chromosomal DNA into the fusion hybrids (so called 'cybrids') and c) this method transfers functional nuclear genes together with the partial genome from the irradiated partner. PMID- 24241799 TI - Relative performance of monohaploid potato clones and their diploid parents at plant level and after protoplast isolation and subsequent fusion. AB - Plant growth performance was studied in 118 potato monohaploids and in their diploid parents. Of these monohaploids 76 were also investigated at the protoplast level and eight of these were used in protoplast fusion experiments as well. No correlation was found between relative performance of greenhouse grown and in vitro grown plants. No or only weak correlations were found between different in vitro characteristics such as plant growth, protoplast yield per gram plant material, plating efficiency and callus growth. This indicates the unpredictability of these characters.The protoplast fusion experiments indicated that only in some genotype combinations increased callus growth rates may be found. However, it is not clear whether such calli were hybrids or not. In protoplast monocultures only diploid and tetraploid regenerants were obtained. After fusion, tetraploids but also some triploids could be regenerated. The finding of triploids indicates that monoploid protoplasts were involved in fusion. Isozyme analysis and morphological assessment of the plants pointed out that the majority of the fusion regenerants were hybrids. The implications of these results are discussed. PMID- 24241800 TI - Interaction between genes controlling a new group of glutenin subunits in bread wheat. AB - One-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) of reduced total protein extracts from the endosperm of hexaploid wheat revealed a new set of faintly-stained bands, having slower electrophoretic mobility than the high-molecular-weight (HMW) glutenin subunits. These new bands have been termed the E group of glutenin subunits. Analysis of aneuploid stocks of Chinese Spring wheat has shown that three of the E bands, in order of increasing electrophoretic mobility, are controlled by genes on the short arms of chromosomes 1B, 1A and 1D, respectively. The E bands are expressed only in the presence of the long arm of chromosome 1B indicating an interaction between two or more genes involved in their production in wheat endosperm. The gene on the short arm of chromosome 1D controlling an E subunit recombined freely with Tri-D1 and the centromere but not at all with Gli-D1, indicating additional complexity at the Gli-DI locus in wheat. PMID- 24241801 TI - Enhanced cross pollination to widen the scope of breeding in groundnut (Arachis hypogaea L.). AB - Six groundnut genotypes belonging to the Virginia and Valencia sub-groups were irradiated with gamma rays at doses of 5, 10, 15 and 20 kR, much below LD50, and grown surrounded by a pollen parent in a split-plot design. The succeeding two generations were checked for the occurrence of hybrids by examining the segregation for pod and seed characteristics and the two quantitative characters, pod and seed yield. Cross-pollination up to 20.8% was observed in 'M13', a Virginia cultivar. There was a genotype-dose interaction for the extent of cross pollination. Cross-pollination was higher in Virginia than Valencia genotypes and more frequent under 15 and 20 kR than under other doses, in general. The observed substantial enhancement of cross-pollination encourages the use of seed irradiation at proper doses as a method for increasing recombination in plant breeding programmes. PMID- 24241802 TI - Stability of deletion, insertion and point mutations at the bronze locus in maize. AB - Phenotypic revertants from several kinds of mutations, including deletions, have been detected by pollen analysis at the wx and Adh loci in maize. Mutations in these genes give phenotypic revertants with median frequencies of 0.7 and 0.5*10( 5), respectively. However, the nature of such revertants can only be analyzed following their recovery from conventional matings. In the current study large seed populations derived from crosses involving several bz (bronze) locus mutations in maize were examined for reversion to a Bz (purple) expression. Deletion, insertion and point mutations were included in the study. Principally, over 2 million gametes of the bz-R mutation, which is shown here to be associated with a 340 base pair deletion within the transcribed region of the gene, have been screened for reversion. No revertants from it or any of the other bz mutations have been recovered, even though a total of almost 5 million gametes from homoallelic crosses have been examined to date. Results from seed analysis are discussed in reference to those from pollen analysis in maize. PMID- 24241803 TI - Genetic structure of the R-Navajo allele in maize, Zea mays L. AB - Mutational and recombinational analyses carried out with the R-nj allele in maize to elucidate the genetic mechanism involved in unique pattern formation and origin of occasional self-coloured kernels in this stock revealed that R-nj represents a complex with two closely linked discrete components. The self-colour (Sc) component is responsible for anthocyanin production and the navajo (Nj) component regulates the time of onset and termination of pigment synthesis restricting the pigmentation to the crown region of the kernel. The probable gene order in the R region of the R-nj:Illinois isolate is: G-Sc-Nj-K. PMID- 24241804 TI - Herbicide tolerant regenerates of potato. AB - Culture-derived plants and cell cultures of potato (Solanum tuberosum L.) respond to the application of the herbicides SYS 67 ME (MCPA) and OMNIDEL (Na-2,2 dichloropropionate) in a comparable fashion. By gradually increasing the herbicide concentration, cell lines were developed which tolerated 50 mg/l of ME or 300 mg/l of OMNIDEL. Any further increase in concentration resulted in the death of all cell cultures. From cell cultures that had been able to grow on media supplemented with 30 mg/l of ME, regenerate plants were obtained that were also tolerant to this concentration. This new trait was retained even after repeated vegetative propagation of the plants. PMID- 24241805 TI - Wide hybridization in okra. AB - Crosses were made between members of the two West African okra types 'Soudanien' and 'Guineen'. All crosses succeeded in both directions and the F1 plants which showed hybrid vigour for plant stature were partially sterile. Cytological observations of the F1 plants revealed abnormal meiosis which resulted in the production of microspores of variable sizes. The frequency of viable pollen (as indicated by acetocarmine staining) was low in the hybrids: 35.80% (U.I.92* U.I.313) and 39.41% (1bk-1*U.I.215). The number of seeds produced per fruit was low in the hybrids and only a few of these seeds are viable. The possibility of gene transfer between the two okra types was discussed. PMID- 24241806 TI - Monosomic analysis of heading date and spikelet number in the common wheat (Triticum aestivum L.) multispikelet line 'Noa'. AB - Genetic analysis of heading date and spikelet number was carried out in the common wheat (Triticum aestivum L.) multispikelet line 'Noa', by using the monosomic series of the regular line 'Mara'. 'Noa's' high number of spikelets was found to be controlled by a recessive major gene on chromosome 2D; a slight reduction in spikelet number was induced by another recessive gene on 'Noa's' 7A chromosome. 'Noa's' late heading date was found to be controlled by two recessive genes, located on chromosome 2D (a major effect) and 6B (a minor effect). The nature of the genes located on 'Noa's' 2D chromosome and the relationship between spikelet number and heading date are discussed. PMID- 24241807 TI - Group selection in plant populations. AB - Several mechanisms have been proposed for group selection, to account for the evolution of altruistic traits. One type, Neighbourhood models, suggests that individuals react with those immediately around them, but with no recognition mechanism. The organization of plant populations seems especially favorable for this type of selection. The possibility of Neighbourhood selection was investigated by simulating a plant population. It was possible for an altruistic trait to evolve, though only under restricted conditions. The main requirement was gene flow only by very restricted pollen dispersal, and a high benefit : cost ratio in the altruistic relationship. Under conditions favourable for such evolution, the starting frequency of the allele, the initial pattern, and the population size, had little effect. Inbreeding tended to prevent the increase of the altruism allele, though this depended on the mechanism of selfing. Known ecological features of plants are discussed that could be considered altruistic and hence require some form of group selection for their evolution, and whether the benefit : cost requirements are likely to be met. Neighbourhood models of group selection are a possibility in plant populations, and we therefore cannot exclude the possibility of altruism in plants. However, Neighbourhood selection is weak force, unlikely to be effective in the face of opposing individual selection. It may be more important as reinforcement of individual selection. PMID- 24241808 TI - Hybrid seed development and viability in crosses of T. aestivum (cv. Chinese Spring) monosomic lines with S. cereale. AB - The diploid and tetraploid wheats have a crossing barrier that inhibits development and viability of the F1 hybrid seeds which result from their pollination with rye. This barrier is ineffective in synthetic or natural hexaploid wheat * rye crosses. From the results obtained by crossing the Chinese Spring monosomic series to a diploid rye composite, it was concluded that the breakdown of this barrier in hexaploid wheats is determined by polygenes, but may also involve genedosage effects. While more than half of the hexaploidwheat chromosomes may contribute to the breakdown of the barrier, chromosome 1D had the strongest effect. Its absence resulted in shrivelled and inviable hybrid kernels similar to those obtained when the T. durum cultivar Langdon was crossed with rye. PMID- 24241809 TI - Endosperm responses to irradiated pollen in apples. AB - The cytological effects of pollen gamma-irradiation at 50 and 100 krad on both embryo and endosperm development were studied in Malus * domestica. Fruit and seed set were reduced by increasing doses of pollen irradiation, while embryo sacs resulting from the treatments differed in number and morphology of endosperm nuclei and in the presence or absence of an embryo. Nuclear abnormalities, distinguished from normal nuclear behaviour in embryo sacs derived from unirradiated pollen, included enhanced numbers of polyploid restitution nuclei, bridges between nuclei, excluded metaphase chromosome fragments and disrupted mitotic synchrony. Generally, a high dose of pollen irradiation (100 krad) generated an all-or-nothing response in the embryo sac, either creating highly abnormal embryos and/or endosperms which aborted, or showing relatively normal development. Callus produced from excised cellular endosperm differed in average genome size, that derived from 100 krad pollen being smaller than that from unirradiated pollen. PMID- 24241810 TI - Yield stability of determinate and indeterminate dry bean cultivars. AB - Yield stability of determinate and indeterminate dry bean (Phaseolus vulgaris L.) cultivars was compared using regression of genotypic performance on environmental means. Yields of 28 dry bean cultivars differing in plant growth habit and commercial class designation were obtained from 42 Michigan performance nurseries over the 6 year period 1980 to 1985. The determinate type I large-seeded kidney and cranberry bean cultivars had below-average seed yield and large mean square deviations from regression. Lower yielding determinate small-seeded navy cultivars had low deviation mean square values, while higher yielding determinate navy cultivars had correspondingly higher mean square deviations from regression. Although seed yield of cultivars with an indeterminate growth habit was greater than determinate cultivars, prostrate type III indeterminate cultivars had deviation mean square values equivalent to those of large-seeded determinate cultivars. The erect, short vine type II indeterminate cultivars (architypes) had greater than average seed yields and minimum deviations from regression. Compared with other plant types, the architype group showed a greater yield response to more productive environments, with regression coefficient values significantly greater than unity. These results indicate that the type II growth habit offers the breeder the best opportunity of obtaining greater seed yield without incurring loss of yield stability as occurs with the type I and type III growth habits. Since the dry bean cultivars utilized in this study represent two distinct centers of domestication, the regression analysis suggests that cultivars from the predominant genetic center demonstrate more yield stability. A non-significant rank correlation coefficient between the combined and separate analyses for deviation mean square values of large-seeded cultivars implies that commercial dry bean classes should be compared separately based on center of domestication. PMID- 24241811 TI - Inheritance of seed weight in Cucumis sativus (L.) var. sativus and var. hardwickii (Royle) Kitamura. AB - A series of experiments was conducted to determine the inheritance of seed weight in cucumber. Matings between a Cucumis sativus var. sativus (Cs) L. inbred line (USDA WI 1606; P1) and a C. sativus var. hardwickii (Royle) Kitamura (Ch) collection (PI 215589; P2) were made to produce seed of reciprocal F1, F2, and BC1 families. Families were grown under field and greenhouse conditions, and seeds were extracted from fruit 55 to 60 days post-pollination. Seed of F1 and F2 families was obtained using the Cs inbred WI2808 (P12) and the Ch collection LJ 90430 (P10), and seed of F1 families were produced using a North Carolina Design II mating scheme in which three Cs (P3= GY-14; P4=WI 1379; P5=WI 1909) inbreds were used as maternal parents and seven Ch collections (P2; P6= PI462369; P7=486336; P8=LJ91176; P9=273469; P10= 2590430; P11=PI187367) were used as paternal parents. Mean seed weights of F1 progeny reflected the dominance of genes of the C. sativus var. sativus parent. Transformation to number of seeds per unit weight resulted in increased variance homogeneity within generations and a broad-sense heritability ranging between 26% to 56%. Additive and dominance effects were important in the expression of seed weight in P1*P2 progeny produced in the greenhouse and additive effects were important in field grown progeny resulting from P1*P2 and P10*P12 matings. The estimated number of factors or loci involved ranged between 10 to 13, depending on the method of calculation. PMID- 24241812 TI - Effects of constitutive heterochromatin and genotype on frequency and distribution of chiasmata in the seven individual rye bivalents. AB - Number and distribution of chiasmata were studied in the single pair of homologous rye chromosomes in 29 chromosomal F1 hybrids between the seven disomic wheat rye addition lines of 'Chinese Spring'/ 'Imperial' and five selected inbred genotypes of cultivated rye by using the differential Giemsa staining technique. The results indicate that the number and position of chiasmata is independent from the amount and position of C-heterochromatin. Genotype had an effect on chiasma number, whereas chiasma distribution within bivalents appeared to be determined by morphological features of chromosomes. Late replicating DNA in constitutive heterochromatin may delay the separation of half bivalents if chiasmata are formed between them and the centromere. PMID- 24241813 TI - Northern hybridization analysis of mitochondria gene expression in maize cytoplasm with varied nuclear backgrounds. AB - Type T cytoplasmic male sterility in Zea mays is associated with mitochondrial RNA (mtRNA) coding sequences found on a 1.5 kb AvaI mitochondrial DNA (mtDNA) fragment not found in other cytoplasms (N, C, or S) (Abbott and Fauron 1986). Three probes (pH3.2N, pH2.7N, and ORF 13) specific to different parts of the 1.5 AvaI T region were used in a Northern blot analysis of N mtDNAs from lines with diverse nuclear backgrounds (Rf1, Rf2 included). The N mtDNA clone pH 3.2N shows homology with the right-hand boundary of the 1.5 AvaI T region and includes a portion of an open reading frame (ORF 25). Southern blots of AvaI and BamH1 digestions of N, T, S, and C mtDNA, probed with pH3.2N demonstrate that sequences in or adjacent to this region are highly active in recombination. The clone pH 2.7N is homologous to an untranscribed region of ATPase 6 and the structural gene; and ORF 13 is a portion of the 1.5 AvaI region derived predominantly from 26S 3' flanking sequences. pH3.2N and 1.5 AvaI sequences showed identical hybridization patterns on Northern blots of N, T, Trev and Tres mtRNAs. Transcript sizes of mtRNAs homologous to the pH 3.2N probe in all of these lines were different, however, there was no variation in transcript sizes when pH 2.7N was used as a probe. Northern blots of mtRNA from N cytoplasms with various nuclear restored backgrounds showed no difference in expression when probed with pH 3.2N or pH 2.7N; however, transcripts homologous to an ORF 13 specific probe can be detected in N cytoplasm with a particular nuclear background. This may suggest activity of nuclear restorer alleles in N cytoplasm. PMID- 24241814 TI - Computational procedure for a weighted diallel analysis. AB - A diallel analysis is described for the case in which the values of the characteristic used in an inheritance study have unequal variances. Such a characteristic can be a mean, a slope of a regression line, or the estimates of some parameter of a linear or nonlinear model. Computational formulae are presented which incorporate the necessary weighting along with the statistics of the Hayman-Jinks method for diallel analysis. The method described can also be used to perform a weighted diallel analysis based on means when there are unequal numbers of replications per cross. A simple example demonstrates the computations necessary to complete a weighted diallel analysis. PMID- 24241815 TI - Immediate and medium-term effects of custom-moulded insoles on pain, physical function, physical activity, and balance control in patients with knee osteoarthritis. AB - OBJECTIVE: To investigate the immediate and medium-term effects of custom-moulded insoles on patients with knee osteoarthritis. DESIGN: Before-after trial, followed up for 6 months. SUBJECTS: Forty participants, mean age 61 years, who fulfilled the combined radiographic and clinical criteria for knee osteoarthritis, as defined by the American College of Rheumatology. METHODS: Custom-moulded insoles with a 5o lateral wedge and arch support were prescribed. Immediate assessment was performed with and without the custom-moulded insoles, and follow-up assessments on pain, balance control, physical function, and physical activity were performed at 1, 3, and 6 months. RESULTS: Significant medium-term effects were represented by reductions in pain (p = 0.003), improved physical functioning (p = 0.006), and decreased chair-rising time (p = 0.016) over the duration of the 6-month follow-up period. Significant immediate increases in physical activity scores for the 10-m normal-speed walking test (p = 0.007), stair-climbing test (p = 0.040), and chair-rising test (p = 0.030) were also observed in patients wearing the custom-moulded insoles, compared with tests performed without the insoles. CONCLUSION: Using custom-moulded insoles provides medium-term pain reduction and improved physical functioning and physical activity, as well as immediate beneficial effects regarding physical activity. PMID- 24241816 TI - Applying discrete choice modelling in a priority setting: an investigation of public preferences for primary care models. AB - OBJECTIVES: The shift toward more innovative and sustainable primary care models in Italy leads policy makers and clinicians to face difficult decisions between options that are all regarded as potentially beneficial. In this study, patient preferences for different primary care models in the Tuscany region of Italy were elicited. The relative importance of different attributes to the surveyed respondents was then examined, as well as the rate at which individuals trade between attributes and the relative value of different service configurations. METHODS: A discrete choice experiment survey explored the following attributes in a stratified random sample of 6,970 adults: primary care provider, diagnostic facilities and waiting time for the visit. RESULTS: Respondents (3,263) were likely to prefer a consultation by their own general practitioner (GP) and a practice with many diagnostic facilities. The predicted utilities of different service configurations have shown that a "primary care centre" with many diagnostic facilities was preferable to a "solo GP" model or a "group general practice". CONCLUSIONS: The study demonstrated how a patient choice model could be used by decision makers for developing successful policies that takes into account different healthcare needs, balancing responsiveness with care continuity, equity and appropriateness. Considering that a primary care centre would perform better than a "solo GP", especially for younger respondents and for those with minor healthcare needs, for a more rapid diffusion of this model policymakers and managers could direct the care of primary care centres towards these targeted subgroups, at least in the first phase. PMID- 24241817 TI - Development and evaluation of the PI-G: a three-scale measure based on the German translation of the PROMIS (r) pain interference item bank. AB - OBJECTIVE: Study aim was to translate the PROMIS((r)) pain interference (PI) item bank (41 items) into German, test its psychometric properties in patients with chronic low back pain and develop static subforms. METHODS: We surveyed N = 262 patients undergoing rehabilitation who were asked to fill out questionnaires at the beginning and 2 weeks after the end of rehabilitation, applying the Oswestry Disability Index (ODI) and Pain Disability Index (PDI) in addition to the PROMIS((r)) PI items. For psychometric testing, a 1-parameter item response theory (IRT) model was used. Exploratory and confirmatory factor analyses as well as reliability and construct validity analyses were conducted. RESULTS: The assumptions regarding IRT scaling of the translated PROMIS((r)) PI item bank as a whole were not confirmed. However, we succeeded in devising three static subforms (PI-G scales: PI mental 13 items, PI functional 11 items, PI physical 4 items), revealing good psychometric properties. CONCLUSION: The PI-G scales in their static form can be recommended for use in German-speaking countries. Their strengths versus the ODI and PDI are that pain interference is assessed in a differentiated manner and that several psychometric values are somewhat better than those associated with the ODI and PDI (distribution properties, IRT model fit, reliability). To develop an IRT-scaled item bank of the German translations of the PROMIS((r)) PI items, it would be useful to have additional studies (e.g., with larger sample sizes and using a 2-parameter IRT model). PMID- 24241818 TI - Domains of quality of life: results of a three-stage Delphi consensus procedure among patients, family of patients, clinicians, scientists and the general public. AB - PURPOSE: Our key objective is to identify the core domains of health-related quality of life (QoL). Health-related QoL utility scales are commonly used in economic evaluations to assess the effectiveness of health-care interventions. However, health-care interventions are likely to affect QoL in a broader sense than is quantifiable with traditional scales. Therefore, measures need to go beyond these scales. Unfortunately, there is no consensus in the scientific literature on the essential domains of QoL. METHODS: We conducted a three-stage online Delphi consensus procedure to identify the key domains of health-related QoL. Five stakeholder groups (i.e., patients, family of patients, clinicians, scientists and general public) were asked, on three consecutive occasions, what they perceive as the most important domains of health-related QoL. An analysis of existing (health-related) QoL and well-being measurements formed the basis of the Delphi-procedure. RESULTS: In total, 42 domains of QoL were judged, covering physical, mental and social aspects. All participants rated 'self-acceptance', 'self-esteem' and 'good social contacts' as essential. Strikingly, mental and social domains are perceived as more essential than physical domains across stakeholders groups. CONCLUSIONS: In traditionally used health-related QoL utility measures, physical domains like 'mobility' are prominently present. The Delphi-procedure shows that health-related QoL (utility) scales need to put sufficient emphasis on mental and social domains to capture aspects of QoL that are essential to people. PMID- 24241819 TI - Measurement properties of the Adolescent Quality of Life Mental Health Scale (AQOL-MHS). AB - BACKGROUND: This article presents data on the psychometric properties of a new measure, the Adolescent Quality of Life Mental Health Scale (AQOL-MHS), designed to measure quality of life in clinical samples of Latino adolescents aged 12-18 years. Participants were recruited in Puerto Rico to have one of five prevalent mental health disorders. The initial instrument development was achieved through a grounded theory approach with the use of focus groups and in-depth interviews. METHODS: We conducted two stages of exploratory factor analyses (EFA) on 60 candidate items. The first stage was to establish the number of factors to extract, and the second was to improve the model by selecting the best items. A final EFA model retained 31 items and 3 factors labeled Emotional Regulation (11 items), Self-Concept (10 items) and Social Context (10 items). RESULTS: The instrument showed good internal consistency, test-retest reliability, and construct validity. The hypotheses-driven validity tests were all supportive of the AQOL-MHS. There was evidence for convergent validity and discriminant validity, and results for known-groups' validity were overwhelmingly supportive of the ability of the instrument to identify differences between groups. CONCLUSIONS: These preliminary findings support our conceptual model and the use of the AQOL-MHS domain and overall scores. We believe that this instrument will provide clinicians additional insight into the different aspects of quality of life that are important to adolescents with mental health problems. Therefore, we consider the AQOL-MHS a vital patient-centered outcome measure for assessment strategies in the prevention and treatment of this population. PMID- 24241820 TI - Assessing conduct disorder: a new measurement approach. AB - The Delinquent Activities Scale (DAS) was used to develop indicators of conduct disorder (CD) in terms of symptom severity and age of onset. Incarcerated adolescents (N = 190) aged 14 to 19 were asked about their delinquent behaviors, including age the behavior was first performed, as well as substance use and parental and peer influences. Assessments were performed for the 12 months prior to incarceration and at 3-month postrelease follow-up. Evidence supports the utility of the DAS as a measure of CD diagnosis, including concurrent incremental validity. Furthermore, CD severity (symptom count) was significantly associated with two peer factors: friend substance use and friend prior arrests, with medium to large effect sizes (ESs). Earlier age of CD onset was associated with earlier marijuana use. This study finds that the DAS is a useful instrument in that it is easy to apply and has adequate psychometrics. PMID- 24241821 TI - Subserosal leiomyoma of uterus mimicking an ovarian tumor in adolescent patient. AB - Uterine leiomyomas are the most common gynecological tumors in adult women. These benign tumors are rarely seen in the adolescent population: there are only a few cases that have been reported so far in this age group. In this case report, we present a giant uterine leiomyoma that mimicked an ovarian tumor in a 15-year-old girl. PMID- 24241822 TI - Does ceruloplasmin differential express in the brain of Ts65Dn: a mouse mode of Down syndrome? AB - To investigate the expression of CP in Down syndrome (DS) mouse model, we especially observed the changes in neuronal CP. We systematically analyzed the level of CP in Ts65Dn mouse, including serum CP concentration and enzymatic activity, CP mRNA in brain, the expression of CP protein in brain. The applied technologies were ELISA, chemical colorimetry, RT-PCR, immunohistochemistry. Compared with the control group, there were no differences of significance in the concentration, enzymatic activity and unit activity of serum ceruloplasmin. By RT PCR, we also found there were no significant differences in the level of CP mRNA. The expression of CP was positive in the endochylema of neuronal cells of both the groups, and there were no significant difference between the two groups. Meanwhile, there were no differences in four regions of the brain (cerebral cortex, hippocampus, thalamus and cerebella). Although the neurotoxic effects of CP related to some neurodegenerative diseases, but whether it does so in DS remains to be determined. PMID- 24241824 TI - Effect of coumarin and xanthotoxin on mitochondrial structure, oxygen uptake, and succinate dehydrogenase activity in onion root cells. AB - At concentrations in which they occur on the plant surface and retard mitosis, coumarin and xanthotoxin lowered uptake of oxygen (by 60 and 30%, respectively) by meristematic cells ofAllium cepa root tips. They caused changes in the structure of the mitochondrial matrix to become dense, and protrusions of mitochondrial membranes were visible parallelling their hypertrophy, indicating alteration in the structure and physiology of these organelles. Coumarin and, to a lesser extent, xanthotoxin increased succinate dehydrogenase production in mitochondria and also in the cytoplasm, indicating changes in membrane permeability. Changes in oxygen uptake and mitochondrial structure, in addition to the retardation of mitosis, may be the reason these compounds act as allelochemicals after they have been removed from the plant surface and reach the root meristem. PMID- 24241823 TI - The crystal structure of sterol carrier protein 2 from Yarrowia lipolytica and the evolutionary conservation of a large, non-specific lipid-binding cavity. AB - Sterol carrier protein 2 (SCP2), a small intracellular domain present in all forms of life, binds with high affinity a broad spectrum of lipids. Due to its involvement in the metabolism of long-chain fatty acids and cholesterol uptake, it has been the focus of intense research in mammals and insects; much less characterized are SCP2 from other eukaryotic cells and microorganisms. We report here the X-ray structure of Yarrowia lipolytica SCP2 (YLSCP2) at 2.2 A resolution in complex with palmitic acid. This is the first fungal SCP2 structure solved, and it consists of the canonical five-stranded beta-sheet covered on the internal face by a layer of five alpha-helices. The overall fold is conserved among the SCP2 family, however, YLSCP2 is most similar to the SCP2 domain of human MFE-2, a bifunctional enzyme acting on peroxisomal beta-oxidation. We have identified the common structural elements defining the shape and volume of the large binding cavity in all species characterized. Moreover, we found that the cavity of the SCP2 domains is distinctly formed by carbon atoms, containing neither organized water nor rigid polar interactions with the ligand. These features are in contrast with those of fatty acid binding proteins, whose internal cavities are more polar and contain bound water. The results will help to design experiments to unveil the SCP2 function in very different cellular contexts and metabolic conditions. PMID- 24241825 TI - 2-(E)-nonen-1-ol: Male attractant for chafersAnomala vitis Fabr. andA. dubia Scop. (Coleoptera: Scarabaeidae). AB - Traps baited with 2-(E)-nonen-1-ol alone or in combination with other compounds caught large numbers of males of both the vine chafer,Anomala vitis Fabr. and the margined vine chafer,A. dubia Scop. (Coleoptera: Scarabaeidae), vineyard and orchard pests. In a dosage test, the largest numbers were caught by traps baited with 10 mg of 2-(E)-nonen-1-ol, which was the highest dosage tested. This is the first report on male attractants for chafer species occurring in Europe. PMID- 24241826 TI - Chemical characterization of urinary volatile compounds ofPeromyscus californicus, a monogamous biparental rodent. AB - The urinary profiles of adult female and male California mice were examined to determine the volatile compounds that may affect reproduction. The urinary volatiles identified by gas chromatography-mass spectrometry (GC-MS) include ketones, pyrazines, alkanes, nitrile, and aldehyde. None of volatile compounds was specific to males or females. The concentration of urinary volatiles in pregnant and lactating females was significantly higher than in virgin females. Male urinary volatile concentrations were similar to those of pregnant and lactating females. The GC profiles of both sexes were distinguished by a high percentage (36%) of pyrazine derivatives that were also in unusually high concentrations. These compounds may play a wide-ranging role in the control of reproduction in the California mouse. PMID- 24241828 TI - Release of ethylene from pruned olive logs: Influence on attack by bark beetles (Coleoptera, Scolytidae). AB - In recently pruned olive logs, an increase in ethylene release has been observed between 48 and 72 hr after pruning. The values reached, as well as the duration of ethylene release, varied greatly from one log to another. PioneerPhloeotribus scarabaeoides females have shown a preference for logs in which ethylene emission was higher. In logs treated with ethrel, a significant increase in ethylene emission was observed, together with a greater period of release. Therefore, the use of logs treated with ethrel could be of great importance in the control of this pest of olive trees. PMID- 24241827 TI - Sex pheromone components of the spring hemlock looper,Lambdina athasaria (Walker) (Lepidoptera: Geometridae). AB - Two methylated hydrocarbons, 7-methylheptadecane (7) and 7,11-dimethylheptadecane (7,11), are female sex pheromone components of the spring hemlock looper (SHL),Lambdina athasaria (Walker). Compounds extracted from female pheromone glands were identified by coupled gas chromatographic-electroantennographic detection (GC-EAD) and coupled GC-mass spectrometry (GC-MS) in selected ion monitoring mode. In field trapping experiments, (7) and (7,11) by themselves were behaviorally inactive, but in combination attracted numerous male moths. (5,11) Dimethylheptadecane (5,11) was detected in female SHL pheromone gland extracts, but did not enhance attraction to the binary blend of (7) and (7,11). The sex pheromone of SHL is related to that of congeneric eastern hemlock looper (EHL),Lambdina fiscellaria fiscellaria (Guen.) [(5,11) and 2,5 dimethylheptadecane (2,5)] and western hemlock looper (WHL),L.f. lugubrosa (Hulst) [(5,11), (2,5) and (7)]. Specificity of the pheromonal blend, spatial separation of coseasonal EHL and WHL, and temporal separation of sympatric EHL and SHL contribute to reproductive isolation. PMID- 24241829 TI - Sequestration of host-plant-derived flavonoids by lycaenid butterflyPolyommatus icarus. AB - Larvae of the lycaenid butterflyPolyommatus icarus were reared on inflorescences ofCoronilla varia andMedicago sativa, which are rich in flavonoids. Twelve different flavonoids (five compounds from the former and nine from the latter), including aglycones andO-glycosides of kaempferol, quercetin, and myricetin were isolated and identified by spectroscopic means. NMR and MS data for the new acylated glycoside kaempferol 3-O-6"-(3-hydroxy-3-methylglutaroyl)-beta-D glucopyranoside are reported. Comparative HPLC analysis of the respective host plants and of larvae, pupae, and imagines ofP. icarus indicated selective uptake and accumulation of kaempferol vs. quercetin and myricetin derivatives. The latter were excreted largely unchanged through the feces. Irrespective of the larval host plant kaempferol 3-O-glucoside was found as the major flavonoid in larvae, pupae, and imagines ofP. icarus, accounting for approximately 83-92% of all soluble flavonoids in adult butterflies. Within the imagines, approximately 80% of all flavonoids are stored in the wings (especially in the orange submarginal lunules), whereas the remaining 20% reside in the bodies. Feeding experiments with artificial diet demonstrated that the insects are able to form kaempferol 3-O-glucoside by glucosylation of dietary kaempferol. Possible functions of the sequestered flavonoids, especially for mate recognition ofP. icarus, are discussed. PMID- 24241830 TI - Homarine as a feeding deterrent in common shallow-water antarctic lamellarian gastropodMarseniopsis mollis: A rare example of chemical defense in a marine prosobranch. AB - The common bright yellow antarctic lamellarian gastropodMarseniopsis mollis was examined for the presence of defensive chemistry. Proton nuclear magnetic resonance (NMR) spectroscopy indicated that a major component of ethanolic extracts purified by reversed-phase column chromatography was homarine. Further high-performance liquid chromatography (HPLC) analysis of the mantle, foot, and viscera verified the presence of homarine in all body tissues at concentrations ranging from 6 to 24 mg/g dry tissue. A conspicuous macroinvertebrate predator of the shallow antarctic benthos, the sea starOdontaster validus, always rejected live individuals ofM. mollis, while readily feeding on pieces of fish tail muscle. Filter paper disks treated with shrimp elicited a broad range of feeding behaviors in the sea starO. validus (movement of disc to mouth, extrusion of cardiac stomach, humped feeding posture). Shrimp disks treated with homarine (0.4 and 4 mg/disk) were rejected byO. validus significantly more frequently than control disks treated with solvent carrier and shrimp or shrimp alone. The highest concentration of homarine tested not only caused feeding deterrence, but in several sea stars a flight response was noted. Homarine was not detected in the tunic of the antarctic ascidianCnemidocarpa verrucosa, a presumed primary prey ofM. mollis. Nonetheless, crude extracts of the epizooites that foul the tunic (primarily the bryozoans and hydroids) contain homarine, suggestingM. mollis may ingest and derive its chemistry from these organisms. This appears to be only the third example of chemical defense in a member of the Order Mesogastropoda. As the vestigial internalized shell ofM. mollis is considered a primitive condition, the findings of this study lend support to the hypothesis that chemical defense evolved prior to shell loss in shell-less gastropods. PMID- 24241831 TI - Influence of oleoresin constituents fromPinus ponderosa andPinus jeffreyi on growth of mycangial fungi fromDendroctonus ponderosae andDendroctonus jeffreyi. AB - Dendroctonus jeffreyi andD. ponderosae are morphologically similar sympatric species of pine bark beetles over portions of their geographic ranges; however,D. jeffreyi is monophagous onP. jeffreyi whileD. ponderosae is highly polyphagous. Both species carry a species of mycangial fungi that are also very similar in appearance. Growth of the two mycangial fungi and of the fungusLeptographium terebrantis (associated with the polyphagous and non-tree-killingDendroctonus valens) in the presence of oleoresin constituents of host and nonhost conifers was tested by placing individual chemicals on agar growth medium and by growing the cultures in saturated atmospheres of the chemicals. The fungus associated withD. jeffreyi showed greater tolerance for chemical constituents placed on the growth medium than the other two fungi, and growth after three days was enhanced by heptane, the dominant constituent ofP. jeffreyi oleoresin. Growth of all three species of fungi was reduced by the resin constituents when the chemicals were presented as saturated atmospheres. The results suggest that the influence of the tree on growth of the symbiotic fungi of the bark beetles during the initial attack process may be different than after colonization by the beetles is complete. The difference in the responses of the apparently related species of mycangial fungi may provide some new insight into the evolutionary history of these beetle/mycangial fungus/host tree systems. PMID- 24241832 TI - Winter host component reduces colonization by bird-cherry-oat aphid,Rhopalosiphum padi (L.) (homoptera, aphididae), and other aphids in cereal fields. AB - Methyl salicylate, a volatile component ofPrunus padus, the winter host ofRhopalosiphum padi, was found to reduce colonization of the summer host by this aphid. The compound was identified by gas chromatographic analysis coupled with recordings from cells in the primary rhinarium on the sixth antennal segment of the aphid. Methyl salicylate eliminated the attractancy of oat leaves to spring migrants in olfactometer tests. In Sweden, this compound significantly decreased colonization of field grown cereals byR. padi and in the U.K., populations ofSitobion avenae andMetopolophium dirhodum were significantly lower on treated plots. PMID- 24241833 TI - Differential induction of tomato foliar proteins by arthropod herbivores. AB - The effects of mechanical and chemical damage and three types of biotic damage on the activities of four foliar proteins of the tomato plant (Lycopersicon esculentum Mill var. Castlemart) were assayed. Proteinase inhibitor, polyphenol oxidase, peroxidase, and lipoxygenase activities were assayed in damaged leaflets and compared with activities in undamaged leaflets. These proteins are putative plant defenses in tomato. Differential induction of these proteins by the various damage-treatments was demonstrated, such that different subsets of the four proteins were induced by different types of damage. This study clearly demonstrates the ability of plants to respond differentially to different types of damage. Possible mechanisms for this differential induction and the implications of differential induction for plant defense are discussed. PMID- 24241834 TI - Male lures for mediterranean fruitfly (Ceratitis capitata wied.): Structural analogs of alpha-copaene. AB - Nine sesquiterpenes structurally related to the potent male Mediterranean fruit fly lure (+)-alpha-copaene were tested in a series of field bioassays to determine their male medfly attractiveness relative to one another and to (+) alpha-copaene itself. This study was carried out to determine the relative importance of the various substructure components of the (+)-alpha-copaene molecule in eliciting an attractive response in the male fly. Tests indicated that any deviation from the three-dimensional structure of (+)-alpha-copaene leads to major losses in male fly attractancy. The tested analogs fell into two groups, based on their levels of attraction: (+)-alpha-ylangene, (+)-beta copaene, (+)-beta-ylangene, and (-)-alpha-copaene were found to be somewhat attractive, although much less so than (+)-alpha-copaene, while (+) cyclosativene, (+)-cyclocopacamphene, (+)-longicyclene, (+)-longipinene, and (-) trans-alpha-bergamotene were not attractive. PMID- 24241835 TI - Repeatability of female response to ipsdienol enantiomeric mixtures by pine engraver,Ips pini (Coleoptera: Scolytidae). AB - Repeatability, a measure of the proportion of variance in a character that occurs among rather than within individuals, is assessed for the phenotypic trait of female response preference for enantiomeric blends of ipsdienol inIps pini at two pheromone concentrations-1 ug and 5 MUg of ipsdienol. Average female response shows greater repeatability at the higher pheromone dosage when females are tested in two successive sets of five assays than when assayed in three successive sets or at the lower dosage. Repeatability within each set of five assays is highest for the first set and decreases thereafter. Thus the response phenotype of females for enantiomeric blends of ipsdienol in this experiment is context dependent; female choice of an enantiomeric blend differed between dosages and among sets of assays. PMID- 24241836 TI - Crayfish feeding responses to zebra mussels depend on microorganisms and learning. AB - Three species of crayfish (Orconectes virilis, O. rusticus, andCambarus robustus) were tested for feeding responses to potential food odors from mollusks (either zebra mussels,Dreissena polymorpha, or native gastropods). In all three crayfish species, feeding responses to odor cues were shown only by individuals experienced with feeding on a prey type. Individuals exposed to just the smell of prey organisms did not show feeding responses, indicating the role of associative learning in diet breadth. Establishment of a learned association took more than one feeding experience but once established lasted more than three weeks. When microbial enzymatic degradation of food protein was eliminated, either by UV radiation or microfiltration, feeding responses were eliminated even for crayfish experienced with a prey type. PMID- 24241837 TI - Synthesis and antifungal activity of analogues of naturally occurring botrydial precursors. AB - Analog compounds of the proposed intermediates of the biogenetic pathway to botrydial have been synthesized. These compounds were tested for their potential antifungal activity against the phytopathogenBotrytis cinerea. Our results showed a fungistatic effect of some compounds on mycelium growth. The most significant effect was exerted by 2-alpha-hydroxy-2,3-dihydro-1-epiprobotrydial, which inhibited growth ofB. cinerea. Some aspects of structure-activity relationships are discussed. PMID- 24241838 TI - Intraspecific and interspecific chemoattraction inBiomphalaria glabrata andHelisoma trivolvis (Gastropoda: Planorbidae). AB - A Petri dish bioassay previously used to examine food preferences in planorbid snails was used to study intraspecific and interspecific chemoattraction inBiomphalaria glabrata (albino strain, M-line) andHelisoma trivolvis (Colorado strain) snails.B. glabrata snails showed significant intraspecific chemoattraction in the absence of visual cues and snail thigmotaxis.H. trivolvis snails also showed significant intraspecific chemoattraction. Interspecific chemoattraction between these species occurred in the bioassay, suggesting that the chemoattractants were not species specific. Artificial spring water conditioned by aqueous excretory-secretory products (snail-conditioned water) ofB. glabrata elicited significant intraspecific chemoattraction. However, lipophilic excretory-secretory products ofB. glabrata elicited significant chemorepulsion. Repellant factors in the lipophilic fraction were not characterized. PMID- 24241839 TI - Pheromone chirality of african palm weevil,Rhynchophorus phoenicis (F.) and palmetto weevil,Rhynchophorus cruentatus (F.) (Coleoptera: Curculionidae). AB - There are four stereoisomers of both 3-methyl-octan-4-ol, the aggregation pheromone of the African palm weevil,Rhynchophorus phoenicis (F.) and 5-methyl octan-4-ol, the aggregation pheromone of the palmetto weevil,Rhynchophorus cruentatus (F.). Synthetic stereoisomers of 3-methyl-octan-4-ol and 5-methyl octan-4-ol were baseline-separated on a Cyclodex-B fused silica column. Use of this column in gas chromatographic-electroantennographic detection (GC-EAD) and GC-mass spectrometric (GC-MS) analyses revealed that only one stereoisomer, (3S,4S)-3-methyl-octan-4-ol and (4S,5S)-5-methyl-octan-4-ol, is produced by maleR. phoenicis and maleR. cruentatus, respectively, and elicits good antennal responses by conspecific male and female weevils. In field trapping experiments, withR. phoenicis in Cote d'Ivoire andR. cruentatus in Florida, (3S,4S)-3-methyl octan-4-ol and (4S,5S)-5-methyl-octan-4-ol strongly enhanced attraction of fresh palm tissue, whereas other stereoisomers were behaviorally benign. Stereoisomeric 3-methyl-octan-4-ol and 5-methyl-octan-4-ol may be utilized to monitor and/or manage populations of these two palm weevils. PMID- 24241840 TI - Evidence for volatile chemical attractants in the beetleMaladera matrida argaman (Coleoptera: Scarabaeidae). AB - TheMaladera matrida beetle (Coleoptera, Scarabaeidae, Melolonthinae), a relatively new species to science, was first identified in Israel in 1983. In the course of field observations it was found that adultM. matrida beetles emerged from the soil at sunset to feed and mate. During the first 20 min of flight, most of the beetles were males. The females emerged shortly afterwards, and aggregations numbering 20-30 individuals with equal proportions of males and females were eventually formed on peanut plants. Laboratory olfactometer bioassays showed that peanut leaves (food) attracted both males and females. Field-trapping experiments and olfactometer studies showed thatM. matrida beetles were highly attracted by live virgin females in the presence of food (cut-up peanut leaves). Another set of field trapping experiments indicated that airborne volatiles produced by live virgin females plus food had the same attracting ability as live virgin females plus food. The attraction exerted by the combination of live virgin females and peanut leave volatiles suggests a synergism effect. Accordingly, we propose a two-stage mechanism of chemical communication in theM. matrida beetles: first, the males cause mechanical damage to the host plant to attract both sexes; later, the females emit attractants (sex pheromone) while eating or shortly thereafter. PMID- 24241841 TI - Comparative analysis of steam distilled floral oils of cacao cultivars (Theobroma cacao L., Sterculiaceae) and attraction of flying insects: Implications for aTheobroma pollination syndrome. AB - Steam-distilled floral fragrance oils from nine distinctive cultivars ofTheobroma cacao L. (Sterculiaceae) in Costa Rica were examined with GC-MS to determine whether or not major differences existed among these cultivars for volatile constituents comprising 50% or more of the samples. The cultivars selected for floral oil analyses were chosen to represent diverse cultivars having supposedly different genetic backgrounds and histories of artificial selection for agronomic purposes. Cluster analysis revealed two major groupings of cultivars: those with higher molecular weight dominant compounds, and those having lower molecular weight compounds. Additionally, one cultivar, Rim-100, selected from criollo or ancestral-type cacao in Mexico and resembling criollo in the appearance of flowers and fruits, formed an extreme group having the highest molecular weight profile for major volatile compounds. Based upon these analyses, bioassays using McPhail traps were performed in an abandoned cacao plantation in northeastern Costa Rica during rainy and dry seasons to determine the relative attraction of these oils to flying insects. Bioassays revealed that the Rim-100 cultivar attracted by far the greatest numbers of cacao-associated midges (Diptera: Ceratopogonidae and Cecidomyiidae), as well as stingless bees (Hymenoptera: Apidae: Meliponinae), suggesting that a floral fragrance having high-molecular weight volatiles is more potent as an attractant to flying insects than floral oils having lower-molecular-weight compounds. It is suggested that Rim-100 more closely resembles an ancestral or wild-type cacao than the other cultivars examined, and therefore it is more effective in attracting opportunistic dipteran floral visitors and pollinators than other cultivars in plantation settings. Several of the major volatile compounds found in the floral oils ofT. cacao and other species ofTheobroma occur in mandibular and other exocrine glands in various bees, including stingless bees and halictids, known visitors ofTheobroma flowers. These compounds are particularly present in noncultivated species ofTheobroma and have much more noticeable fragrances than the seemingly scentless flowers of cultivatedT. cacao selected for agriculture. It is hypothesized that the floral attraction system of ancestral or wild (noncultivated)T. cacao and other species ofTheobroma may have evolved to attract certain bees as their principal pollinators in natural habitats in the Neotropics, with a floral reward hypothesized as being sociochemicals needed by bees for mating, foraging, territorial defense, etc. Because of the many generations of extensive selection by cloning for desired cultivars,T. cacao might have lost much of its original floral attraction system for bees, instead being pollinated opportunistically by dipterans in plantation habitats. This may help to explain why natural pollination in cultivatedT. cacao is generally very poor relative to observed levels of fruit-set in wild or noncultivated species ofTheobroma. PMID- 24241842 TI - Moth responses to selectively fluorinated sex pheromone analogs. AB - Partially fluorinated analogs of the European corn borer (Ostrinia nubilalis) female sex pheromone, 11-tetradecenyl acetate (97:3Z:E), having mono- and trifluorsubstitutions at the terminal carbon of the pheromone chain, mimicked the biological activity of the pheromone, while analogs with fluorine at either side of the double bond and a pentafluoro analog were essentially inactive. Comparison of the pheromonal activity of these analogs with the previously reported activity of similarly fluorinated pheromones in five other species of moths revealed an unpredictable relationship between fluorine substitution pattern and pheromone mimicking activity. Fluorine substitution patterns that rendered pheromonal analogs biologically inactive in the European corn borer had no detrimental influence upon pheromonal activity in other species and the converse was also true. This is evidence that the relative importance of electronic qualities of sites within a pheromone molecule differ from species to species. Furthermore, it indicates that the biochemical components (pheromone receptor proteins, binding proteins, and enzymes) that make up moth olfactory chemosensory systems must also vary structurally from species to species, despite the fact that they are involved in olfactory sensing of compounds having very similar chemical structure. PMID- 24241843 TI - Major component in male sex pheromone of cereal pestEurygaster integriceps puton (Heteroptera: Scutelleridae) identified as a homosesquiterpenoid. AB - A homosesquiterpenoid, (4Z,4'E)-4-(1',5'-dimethyl-4'-heptenylidene)-1 methylcyclohexene, has been identified as a major component of the scent emitted by calling males ofEurygaster integriceps. Minor components of the scent included vanillin. TheE. integriceps male homosesquiterpenoid is an addition to the list of sesquiterpenoids identified as components of male attractant sex pheromones in pentatomoid Heteroptera. PMID- 24241844 TI - Effect of temperature on biosynthesis of sex pheromone components in potato tuberworm moth,Phthorimaea operculella (Lepidoptera: Gelechiidae). AB - Rearing temperature modified the sex pheromone component ratio in the potato tuberworm moth,Phthorimaea operculella. This phenomenon seemed to be induced with ambient temperature by differences in timing and speed of biosynthesis between two pheromone components. (E,Z,Z)-4,7,10-Tridecatrienyl acetate (triene) was mainly synthesized during the pupal period, while most of (E,Z)-4,7-tridecadienyl acetate (diene) was synthesized during a short period just after emergence. Therefore, the ratio of triene in a newly emerging adult was relatively high at all temperatures although the amount of triene was relatively low at 35 degrees C. On the other hand, the synthetic rate of accumulation of diene was clearly modified by ambient temperature. Biosynthesis of diene at 15 degrees C was very low in the first two days and high in the third day. Consequently, a titer of the diene component at 15 degrees C became approximately equivalent to that at 25 degrees C one day later. PMID- 24241845 TI - Integumental slime and wax secretion: Defensive adaptations of sawfly larvae. AB - Evidence is presented from predation tests with ants (Formica exsectoides) that the slimy coating ofCaliroa cerasi and the waxy investiture ofEriocampa ovata serve in defense. PMID- 24241846 TI - Ethylene biosynthesis in isolated vacuoles of Vicia faba L. - requirement for membrane integrity. AB - The ability of vacuoles prepared from V. faba leaves to convert 1 aminocyclopropane-1-carboxylic acid to C2H4 was destroyed when vacuoles were lysed by passage through a hypodermic needle, freezing and thawing, osmotic shock, treatment with ethanol or with a detergent. Ethylene synthesis in the vacuolar fraction was also inhibited by the uncouplers carbonyl cyanide m chlorophenyl hydrazone and dinitrophenol and by the ionophores valinomycin, nigericin, and A23187. Ethylene formation increased with increasing pH of the incubation medium over the pH range of 5.0-7.5. These observations support the hypothesis that C2H4 biosynthesis in vacuolar preparations is dependent on membrane integrity, possibly because of the requirement for a transmembrane ion gradient. PMID- 24241847 TI - Partial purification and characterization of mRNAs encoding glycollate oxidase and catalase. AB - Polyadenylated mRNA was prepared from etiolated and greening leaves of Lens culinaris and cotyledons of Cucumis sativus during the transition from etiolated to photoautotrophic stage. These mRNA preparations were used to identify, by translation in vitro, the precursor forms of glycollate oxidase and catalase, both enzymes being markers of microbodies. The level (per fresh weight) of translatable RNA coding for glycollate oxidase was found to increase ten fold during the first 3 d of illumination of etiolated leaves. For catalase mRNA activity, this increase was less pronounced. Characterizing the products of in vitro translation directed by the mRNA prepared, we observed a 43-kDa species of glycollate oxidase and a 56-kDa species of apo-catalase. Limited proteolysis of the in-vitro-formed proteins and comparison with the respective mature enzymes present in vivo revealed differences between the cucumber and the lens protein but not between the monomeric precursor and the subunit of mature glycollate oxidase from Lens culinaris. Messenger RNA coding for glycollate oxidase was highly purified by electrophoresis on low-melting-point agarose in the presence of methylmercuric hydroxide. The size of the mRNA was determined to be 1.47 kb. By this procedure, the mRNA for glycollate oxidase in the subfraction could be enriched in such a way that the activity, assayed by translation in a reticulocyte lysate, amounted to 30% of the total translation activity. PMID- 24241848 TI - Cell-fractionation analysis of glucan synthase I and II distribution and polysaccharide secretion in soybean protoplasts : Evidence for the involvement of coated vesicles in wall biogenesis. AB - The organelles of soybean (Glycine max (L.) Merr.) protoplasts were separated using a recently developed procedure which allows rapid (3-h) recovery of a fraction enriched for coated vesicles (CVs). As determined by marker-enzyme enrichment and ultrastructural analysis of isolated membrane fractions, endoplasmic reticulum, Golgi membranes, glucan-synthase-II (EC 2.4.1.34) containing membranes (putative plasma membrane), mitochondria, and CVs were enriched in separate fractions in a sucrose density gradient. Glucan synthase I (EC 2.4.1.12) had the highest specific activity in the Golgi-enriched and CV enriched fractions and was found to comigrate with CVs upon rate-zonal centrifugation of a CV-enriched fraction. For further elucidation of the role of these latter organelles in cell-wall regeneration, freshly isolated protoplasts were pulsed with [(3)H]glucose for 20 min, and the disappearance of label from the organelles was followed for the ensuing 1 h. Although a CV-enriched fraction contained glucan synthase I, it contained very small amounts of labelled polysaccharide during the period of study. Pulse-chase experiments with [(3)H]glucose helped to confirm the role of the Golgi apparatus in secretion of matrix polysaccharides by protoplasts. PMID- 24241849 TI - Efficient uptake of flavonoids into parsley (Petroselinum hortense) vacuoles requires acylated glycosides. AB - Vacuoles were prepared from cultured parsley cells by polyamine-induced rupture of protoplasts. Acid-phosphatase activity, associated exclusively with the vacuoles, served for determination of vacuole yield in subsequent transport studies. Isolated vacuoles rapidly accumulated [2'''-(14)C]apigenin 7-O-(6-O malonylglucoside) or 2"-(14)C]beta-methyl D-6-O-malonylglucoside added at approximately 20 nM and 1.5 MUM concentration, respectively, to the incubation mixture. The accumulation was linear with time and strongly dependent on alkaline buffer conditions as well as on the age of the vacuole preparation. Subsequent addition of a malonic hemiester esterase did not relase the label from the vacuoles. Moreover, neither [2-(14)C]apigenin 7-O-glucoside or [2-(14)C]malonic acid accumulated in the vacuoles under any assay conditions, nor did such compounds or beta-methyl D-glucopyranoside, a malonic diester, and a succinic monoester inhibit transport of the acylated flavonoid. Transport was, however, inhibited by beta-methyl D-6-O-malonylglucopyranoside. Vacuoles which had been incubated for more than 40 min at pH 8.0 did not stain any more with neutral-red dye and concomitantly lost the previously accumulated acylated glucoside. Our data confirm that malonylglucoside uptake by parsley vacuoles involves selective transport sites. It is suggested that changes in the molecular symmetry of the malonylglucosides are responsible for vacuolar trapping of flavonoids in parsley. PMID- 24241850 TI - Immunochemical studies on xanthine dehydrogenase of soybean root nodules : Ontogenic changes in the level of enzyme and immunocytochemical localization. AB - Xanthine dehydrogenase (XDH, EC 1.2.1.37) was purified from root nodules of soybean (Glycine max) and used to prepare a polyclonal rabbit antiserum. Monospecificity of this antiserum was ascertained by sodium dodecyl sulfate polyacrylamide gel electrophoresis of the immunoprecipate. During root nodule development of soybean, only one form of XDH was detected on an immunological basis. Titration of XDH by immunoelectrophoresis showed that a remarkable increase in the amount of XDH occurred between two and four weeks after inoculation, in parallel with the increase in enzyme activity. Localization of XDH by immunofluorescence indicated that the enzyme was present exclusively in uninfected cells where it appeared to be associated with discrete organellels. PMID- 24241851 TI - Tissue-distribution of secondary phenolic biosynthesis in developing primary leaves of Avena sativa L. AB - Primary leaves of oats (Avena sativa L.) have been used to study the integration of secondary phenolic metabolism into organ differentiation and development. In particular, the tissue-specific distribution of products and enzymes involved in their biosynthesis has been investigated. C-Glucosylflavones along with minor amounts of hydroxycinnamic-acid esters constitute the soluble phenolic compounds in these leaves. In addition, considerable amounts of insoluble products such as lignin and wall-bound ferulic-acid esters are formed. The tissue-specific activities of seven enzymes were determined in different stages of leaf growth. The rate-limiting enzyme of flavonoid biosynthesis in this system, chalcone synthase, together with chalcone isomerase (EC 5.5.1.6) and the terminal enzymes of the vitexin and isovitexin branches of the pathway (a flavonoid O methyltransferase and an isovitexin arabinosyltransferase) are located in the leaf mesophyll. Since the flavonoids accumulate predominantly (up to 70%) in both epidermal layers, an intercellular transport of products is postulated. In contrast to the flavonoid enzymes, L-phenylalanine ammonia-lyase (EC 4.3.1.5), 4 coumarate: CoA ligase (EC 6.2.1.12), and S-adenosyl-L-methionine: caffeate 3-O methyltransferase (EC 2.1.1.-), all involved in general phenylpropanoid metabolism, showed highest activities in the basal leaf region as well as in the epidermis and the vascular bundles. We suggest that these latter enzymes participate mainly in the biosynthesis of non-flavonoid phenolic products, such as lignin in the xylem tissue and wall-bound hydroxycinnamic acid-esters in epidermal, phloem, and sclerenchyma tissues. PMID- 24241852 TI - Developmental and hormonal regulation of beta-1,3-glucanase in tobacco. AB - A highly sensitive and specific "rocket" immunoassay was used to measure the content of an endo-type beta-1,3-glucanase (EC 3.2.1.39) in tissues of Nicotiana tabacum L. cv. Havana 425. We show that the accumulation of beta-1,3-glucanase in cultured pith-parenchyma tissue is blocked by combinations of the auxin, alpha naphthaleneacetic acid (NAA), and the cytokinin, kinetin. When tissues pre incubated for 7 d on complete medium containing 2.0 mg.l(-1) NAA and 0.3 mg.l(-1) kinetin are transferred onto medium without hormones or with either hormone added separately, the beta-1,3-glucanase content expressed per mg soluble protein increases approx. ten fold over a 7-d period. Under these inductive conditions, up to approx. 5% of the soluble protein is beta-1,3-glucanase. The induction is inhibited by >90% when tissues are cultured over the same period on medium containing both hormones. This beta-1,3-glucanase is developmentally regulated in the intact plant. It is a major component of the soluble protien in the lower leaves and roots but is not detectable in leaves near the top of the plant. PMID- 24241853 TI - Evidence for a relationship between malate metabolism and activity of 1 sinapoylglucose: L-malate sinapoyltransferase in radish (Raphanus sativus L.) cotyledons. AB - The control of malate metabolism and stimulation of 1-sinapolyglucose: L-malate sinapoyltransferase (SMT) activity in radish (Raphanus sativus L. var. sativus) cotyledons has been studied. The light-induced and nitrate-dependent activity of SMT catalyzes the formation of O-sinapoly-L-malate via 1-O-sinapoyl-beta-D glucose. When dark-grown radish seedlings, cultivated in quartz sand with nutrient solution containing NO 3 (-) as the sole N source, were treated with light, SMT activity increased concomitantly with free malate in the cotyledons. This light effect was suppressed in seedlings grown in a culture medium which contained in addition to NO 3 (-) also NH 4 (+) . However, treatment with methionine sulfoximine neutralized this ammonium effect, resulting again in both rapid accumulation of malate and rapid increase in SMT activity. When seedlings grown on NO 3 (-) nitrogen were subsequently supplied with NH 4 (+) nitrogen, the accumulated level of L-malate rapidly dropped and the SMT increase ceased. The enzyme activity decreased later on, reaching the low activity level of plants which were grown permanently on NO 3 (-) /NH 4 (+) -nitrogen. An external supply (vacuum infiltration) of malate to excised cotyledons and intact seedings, grown on NO 3 (-) /NH 4 (+) -nitrogen medium, specifically promoted a dose-dependent increase in the activity of SMT. In summary these results provide evidence indicating that the SMT activity in cotyledons of Raphanus sativus might be related to the metabolism of malic acid. PMID- 24241854 TI - Molecular properties of phosphoenolpyruvate carboxylase from C3, C 3-C 4 intermediate, and C 4 Flaveria species. AB - Phosphoenolpyruvate carboxylase (PEPCase; EC 4.1.1.31) from Flaveria trinervia Mohr (C4), F. floridana Johnston (C3-C4), and F. cronquistii Powell (C3) leaves were compared by electrotransfer blotting/enzyme-linked immunoassay (Western-blot analysis), mobility of the native enzyme in polyacrylamide gels and in isoelectric focusing (IEF) gels, peptide mapping, and in-vitro translation of RNA isolated from each plant. The PEPCases from the C3 and C3-C4 plants were very similar to each other in terms of electrophoretic mobilities on gels and isoenzyme patterns on IEF gels, and identical in peptide mapping. Quantitative differences were noted, however, in that the C3-C4 intermediate plant contained more PEPCase overall and that the relative activity of individual isoenzymes shifted between the C3 and C3-C4 intermediate PEPCases. The PEPCase from the C4 plant had a different isoenzyme pattern, a different peptide map, and was far more abundant than the other two enzymes. Western blot analysis demonstrated the cross-reactivity of PEPCases from all three Flaveria species with antibody raised against maize PEPCase. The results provide evidence, at the molecular level, that supports the view of C3-C4 intermediate species as C3-like plants with some C4 like photosynthetic characteristics, but there are differences from the C3 plant in the quantity and properties of the PEPCase from the C3-C4 intermediate plant. PMID- 24241855 TI - The pyridine-nucleotide cycle in tobacco : Enzyme activities for the recycling of NAD. AB - In order to elucidate the NAD-recycling pathway the following enzyme activities have been characterized in different tobacco tissues and in tomato root: NAD pyrophosphatase, nicotinamide mononucleotide (NMN)/nicotinic acid mononucleotide (NaMN) glycohydrolases, nicotinamidase and nicotinic acid phosphoribosyltransferase. The investigations were performed with protein extracts purified by gel filtration and enzymatic activities were determined by high-performance liquid chromatography methods. The kinetic parameters of the different enzymes from tobacco root and their specificity are reported. The data are in favor of the so-called pyridine-nucleotide cycle VI (NAD->NMN >nicotinamide->nicotinic acid->NaMN->nicotinic acid adenine dinucleotide->NAD). In the nicotine-producing tobacco root a further direct route leading from NaMN to nicotinic acid is proposed. These data are reconciled with the assumption that it is nicotinic acid which is provided by the pyridine-nucleotide cycle for the synthesis of nicotine. PMID- 24241856 TI - Thylakoid-protein phosphorylation during the life cycle of Scenedesmus obliquus in synchronous culture. AB - The phosphorylation of thylakoid proteins, which comprise apoproteins of the light-harvesting chlorophyll a/b-protein complex (LHCP), was investigated in vivo and in vitro during the development of Scenedesmus obliquus in synchronous cultures. The in-vitro and in-vivo protein phosphorylation exhibited a maximum activity in cells with maximum photosynthetic capacity (8th hour) and miximum activity in cells with minimum photosynthetic capacity (16th hour). The major phosphorylated polypeptides in vivo were the 24/25-kDa and 28-30-kDa apoprotein of the LHCP, a protein of about 32 kDa, and some smaller polypeptides within the range 10 to 20 kDa. In vitro, the main phosphoproteins were the 28-30-kDa apoprotein and the protein characterized by an apparent molecular weight of 32 kDa. Pulse-chase experiments in vivo established that the latter had the fastest radioactivity turnover of the thylakoidal phosphoproteins. PMID- 24241857 TI - The subcellular location and characteristics of pyrophosphate-fructose-6 phosphate 1-phosphotransferase from suspension-cultured cells of soybean. AB - The cytoplasm was identified as the probable location of pyrophosphate-fructose-6 phosphate 1-phosphotransferase (EC 2.7.1.90) in suspension-cultured cells of soybean (Glycine max L.). The characteristics of the partially purified enzyme were investigated. The activity was strongly dependent on the presence of fructose 2,6-bisphosphate and this activator exerted its effects through a dramatic increase in the affinity of the enzyme for its substrates, fructose 6 phosphate and inorganic pyrophosphate. Saturation curves for all substrates were hyperbolic. The apparent molecular weight of the partially purified enzyme was 183000 by gel filtration chromatography and 128000 by sucrose-density-gradient centrifugation. The activation by fructose 2,6-bisphosphate was not accompanied by any measurable change in molecular weight. The possible role of this enzyme in the metabolism of non-photosynthetic sink tissues is discussed. PMID- 24241858 TI - Hydrogen-peroxide-scavenging systems within pea chloroplasts : A quantitative study. AB - The subcellular distribution of ascorbate peroxidase and glutathione reductase (EC 1.6.4.2) in pea leaves was compared with that of organelle markers. Enzyme distribution was found to be similar to that of the chloroplast enzyme NADPH glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13). Isolated chloroplasts showed a close correlation between intactness and the percentage of enzyme activity recovered. Chloroplasts of 85% intactness were found to contain a high proportion of leaf dehydroascorbate reductase activity (EC 1.8.5.1), 10% of leaf glutathione and 30% of leaf ascorbate. These results are discussed in relation to the potential role of chloroplast antioxidant systems in plant resistance to environmental and other stress conditions. PMID- 24241859 TI - The effect of monensin on intracellular transport and secretion of alpha-amylase isoenzymes in barley aleurone. AB - The effect of monensin on the secretion of alpha-amylase and other enzymes from the aleurone layer of barley (Hordeum vulgare L. cv. Himalaya) was studied by electrophoresis followed by fluorography and by pulse-chase and organelle isolation experiments. Monensin markedly inhibits the secretion, but not the synthesis, of alpha-amylase, acid phosphatase, and at least four other proteins from the aleurone layer. Monensin treatment causes alpha-amylase to accumulate within the protoplast, but its effect on the different alpha-amylase isoenzymes is not equal. The accumulation of isoenzyme 2 is not influenced by monensin while isoenzymes 1, 3 and 4 are not secreted but rather accumulate in the cell when monensin is included in the incubation medium. The alpha-amylase and acid phosphatase activities which accumulate within the aleurone cells following treatment with monensin are localized in an organelle having a buoyant density greater than that of endoplasmic reticulum and less than that of mitochondria. In pulse-chase experiments with [(35)S]methionine, labelled proteins accumulate in this organelle in the presence of monensin and do not appear in the incubation medium. We conclude that monensin inhibits the secretion of proteins from the barley aleurone layer by influencing their intracellular transport. PMID- 24241860 TI - An evaluation of light and CO2 limitation of leaf photosynthesis by CO2 gas exchange analysis. AB - Numerical values which define the relative limitation of photosynthesis by light and CO2 were computed from the slopes of light-and CO2-response curves of photosynthesis. This method offers an easy approach for the characterization of photosynthesis of leaves. PMID- 24241862 TI - Sambucus nigra agglutinin is located in protein bodies in the phloem parenchyma of the bark. AB - The bark of some young woody stems contains storage proteins which are subject to an annual rhythm: they accumulate in the autumn and are mobilized in the spring. We show here that the bark phoem-parenchyma cells of Sambucus nigra L. contain numerous protein bodies, and that the bark lectin (S. nigra agglutinin) which undergoes an annual rhythm is localized in these protein bodies. The protein bodies in the cotyledons of legume seeds also contain lectin, indicating that lectins may be storage compounds themselves or may have a function in storage and or mobilization processes. PMID- 24241861 TI - Copy numbers of chloroplast and nuclear genomes are proportional in mature mesophyll cells of Triticum and Aegilops species. AB - The possibility of estimating the proportion of chloroplast DNA (ctDNA) and nuclear DNA (nDNA) in nucleic-acid extracts by selective digestion with the methylation-sensitive restriction enzyme PstI, was tested using leaf extracts from Spinacia oleracea and Triticum aestivum. Values of ctDNA as percentage nDNA were estimated to be 14.58%+/-0.56 (SE) in S. oleracea leaves and 4.97%+/-0.36 (SE) in T. aestivum leaves. These estimates agree well with those already reported for the same type of leaf material. Selective digestion and quantitative dot-blot hybridisation were used to determine ctDNA as percentage nDNA in expanded leaf tissue from species of Triticum and Aegilops representing three levels of nuclear ploidy and six types of cytoplasm. No significant differences in leaf ctDNA content were detected: in the diploids the leaf ctDNA percentage ranged between 3.8% and 5.1%, and in the polyploids between 3.5% and 4.9%. Consequently, nuclear ploidy and nDNA amount were proportional to ctDNA amount (r(19)=0.935, P>0.01) and hence to ctDNA copy number in the mature mesophyll cells of these species. There was a slight increase in ctDNA copy numbers per chloroplast at higher ploidy levels. The balance between numbers of nuclear and chloroplast genomes is discussed in relation to polyploidisation and to the nuclear control of ctDNA replication. PMID- 24241863 TI - Glycerolipid synthesis by homogenate and oil bodies from developing mustard (Sinapis alba L.) seed. AB - [1-(14)C]Oleic acid and [14-(14)C]erucic acid were converted to their acyl-CoA derivatives and incorporated into acyl lipids by a homogenate from developing mustard (Sinapis alba L.) seed and oil bodies, as well as supernatant isolated by centrifugation at 20000 g. In both homogenate and oil bodies, the oleoyl moieties from exogenous [1-(14)C]oleoyl-CoA were most extensively incorporated into phosphatidic acids, but very little into phosphatidylcholines. The pattern of labelling of acyl lipids by oleoyl versus erucoyl moieties from either of the corresponding fatty acids, added individually or as a mixed substrate, indicates that oleoyl-CoA directly acylates sn-glycerol-3-phosphate to yield lysophosphatidic acids and phosphatidic acids that are subsequently converted to mono- and diacylglycerols. In contrast, erucoyl-CoA predominantly acylates preformed mono-and diacylglycerols containing oleoyl moieties to yield triacylglycerols containing erucoyl moieties. PMID- 24241864 TI - Mass-spectrometric evidence for the double-carboxylation pathway of malate synthesis by Crassulacean acid metabolism plants in light. AB - Phyllodia of the Crassulacean acid metabolism (CAM) plant Kalanchoe tubiflora were allowed to fix (13)CO2 in light and darkness during phase IV of the diurnal CAM cycle, and during prolongation of the regular light period. After (13)CO2 fixation in darkness, only singly labelled [(13)C]malate molecules were found. Fixation of (13)CO2 under illumination, however, produced singly labelled malate as well as malate molecules which carried label in two, three or four carbon atoms. When the irradiance during (13)CO2 fixation was increased, the proportion of singly labelled malate decreased in favour of plurally labelled malate. The irradiance, however, did not change either the ratio of labelled to unlabelled malate molecules found in the tissue after the (13)CO2 application, or the magnitude of malate accumulation during the treatment with label. The ability of the tissue to store malate and the labelling pattern changed throughout the duration of the prolonged light period. The results indicate that malate synthesis by CAM plants in light can proceed via a pathway containing two carboxylation steps, namely ribulose-1,5-bisphosphate-carboxylase/oxygenase (EC 4.1.1.39) and phosphoenolpyruvate carboxylase (EC 4.1.1.31) which operate in series and share common intermediates. It can be concluded that, in light, phosphoenolpyruvate carboxylase can also synthesize malate independently of the proceeding carboxylation step by ribulose-1,5-bisphosphate carboxylase/oxygenase. PMID- 24241865 TI - Enzyme activities in an artificial stroma medium : An experimental model for studying effects of dehydration on photosynthesis. AB - When spinach leaf tissue was subjected to evaporative dehydration, photosynthetic capacity at very high (5%) CO2 concentration and saturating irradiance (300 W.m( 2)), decreased in parallel to the relative water content (RWC). A 50% inhibition was observed at 60-40% RWC. In order to examine whether the inhibition was caused by increased solute concentrations in chloroplasts or cytoplasm, an artificial stroma medium (ASM) was set up containing all major osmotically relevant solutes measured in isolated intact spinach chloroplasts. Subsequently, the response of enzyme activities to normal and to increased concentrations of ASM was examined. Inhibition of enzymes by a concerted increase of all solutes was well correlated to the in-vivo response of photosynthesis to dehydration (60% inhibition at double-strength ASM). Inhibitory solutes were mainly divalent inorganic anions, such as sulfate and phosphate. Inhibition of ribulose-1,5-bisphosphate carboxylase by these ions as studied in more detail. Inhibition of the enzyme by sulfate and phosphate was competitive with respect to ribulose-1,5-bisphosphate, but not with respect to CO2. The KI for sulfate was 2.1 mmol.l(-1) and for phosphate 0.57 mmol.l(-1). Sugars and amino acids at the concentrations found in spinach chloroplasts did not prevent inhibition of enzymes by anions. The results indicate that increased anion concentrations in cells and organelles are responsible for primary, quickly reversible effects of moderate dehydration on plant tissues. PMID- 24241866 TI - Occurrence of diamine oxidase in the apoplast of pea epicotyls. AB - Most of the diamine oxidase (EC 1.4.3.6) present in pea (Pisum sativum L. cv. Rondo) epicotyls is found in the fluid obtained by centrifuging pea epicotyl sections previously infiltrated under vacuum with a buffer solution. No detectable amount of the cytoplasmic enzyme glucose-6-phosphate dehydrogenase is present in this fluid, showing that there is very little contamination by cell contents. Polyacrylamide-gel electrophoresis and specific-activity data indicate that diamine oxidase is the most plentiful protein in the extracellular solution obtained from pea epicotyl sections and that an active process is involved in the selective transfer of the enzyme outside the cell. The possible involvement of diamine oxidase in the supply of H2O2 to peroxidase-catalyzed reactions occurring inside the cell wall is discussed. PMID- 24241867 TI - Intranuclear microinjection for transformation of tomato callus cells. AB - An efficient method, called the culture plate method, was devised for microinjection of foreign materials into nuclei of tomato callus cells. The culture plate method, used in this study, is advantageous because cells suitable for microinjection can be selected microscopically and the injected cells subsequently cultured in the same plate. With this microinjection system, some foreign materials were injected into nuclei of callus cells without causing detrimental effects. Kanamycin-resistant callus clones were obtained 1 month after injection from single cells whose nuclei were microinjected with a NPT II DNA fragment of the pE2KX plasmid. PMID- 24241868 TI - Regeneration of amphidiploid plants from tissue cultures of Allium wakegi. AB - Callus was induced from the bulb of Allium wakegi Araki on MS semisolid medium supplemented with several growth regulating substances. The calli were subcultured every 40 days. At the time of every subculture the callus was subdivided to be used for chromosome studies, plant regeneration, or continuous callus multiplication. The chromosome constitution of cells in callus and regenerated plants varied over the culture period, and at the 3rd subculture amphidiploid plants were obtained. They appeared even more frequently than amphihaploid plants in the 4th subculture. Hypoamphihaploid regenerants appeared as stumpy shoots but none of these shoots proceeded further to form a normal plant. By Giemsa C-banded karyotype, the chromosome constitution of amphidiploid plants was found to result from exact doubling of the chromosome sets of amphihaploid common species. Amphidiploid plants show better viability and growth than common plants. The possibility and the expectation of new crop plants to be developed from amphidiploid plants will be discussed. PMID- 24241869 TI - Regeneration by somatic embryogenesis of triploid plants from endosperm of walnut, Juglans regia L. cv Manregian. AB - Plants were regenerated by somatic embryogenesis from endosperm tissue of open pollinated seeds of Juglans regia L. cv Manregian. These plants were obtained by growing endosperm tissue on media similar to those used for plant regeneration from walnut cotyledons (Tulecke and McGranahan 1985). The plants appear morphologically uniform and have a triploid chromosome number of 3n=48. Nine plants have been grown to a young sapling stage in soil. This embryogenic line from endosperm has been maintained in culture for two years by the process of repetitive somatic embryogenesis. PMID- 24241870 TI - Growth inhibition by exogenous proline and its metabolism in saltgrass (Distichlis spicata) suspension cultures. AB - The growth of Distichlis spicata suspension cultures in LS medium without NaCl was inhibited 54% by 2 mM proline. In medium containing 260 mM NaCl, 10 mM proline inhibited growth by only 22%. The uptake and metabolism of 10 mM L-[1 (13)C] proline was followed by (13)C NMR and ninhydrin analyses of suspensions cultured in the presence of 0 or 260 mM NaCl. Uptake of 85 to 92% of the exogenous proline occurred within 72 h in all media. In 10 mM proline and no NaCl, cellular proline reached a maximm of 51.5 MUmoles/g FW compared to 1.9 MUmoles/g FW in suspensions not grown on proline. In medium containing 260 mM NaCl and proline, cellular proline reached 59-65 MUmoles/g FW compared to 30-40 MUmoles/g FW in controls grown without proline. The (13)C-label in the proline-C1 was either retained in proline or disappeared, presumably released as carbon dioxide, by catabolism through the TCA cycle. Since no metabolite of (13)C proline was detected by NMR, proline was considered to be the molecule which inhibited the suspension culture growth. PMID- 24241871 TI - Alkaloid production by transformed root cultures of Catharanthus roseus. AB - Transformed roots of Catharanthus roseus were obtained following infection of detached leaves with Agrobacterium rhizogenes. Roots would not grow in full strength Gamborg's B5 medium but would grow satisfactorily if the medium was diluted to one half strength. Little alkaloid appeared in the growth medium but root tissue contained a high level and wide variety of alkaloids. Ajmalicine, serpentine, vindolinine and catharanthine were prominent components. Vinblastine could also be detected by a combination of HPLC and radioimmunoassay, though at a level of only 0.05MUg/g dry weight. PMID- 24241872 TI - Anther culture of some perennial triticeae. AB - Three field grown Agropyron spp. (crested wheatgrasses) and two Thinopyrum spp. (intermediate and tall wheatgrasses) were evaluated for anther culture response. Hormonally modified potato extract and 85D12 media induced pollen embryogenesis. Modified Murashige and Skoog media were tested for their effects on callus proliferation and plantlet regeneration. Callus induction frequency and plantlet production were highest (25.0% and 45.8%, respectively) for Thinopyrum ponticum (2N=70) (tall wheatgrass). One-hundred and nine albino plantlets were produced from T. ponticum 'Jose' both by direct regeneration on 85D12 medium and through a callus phase from potato extract media. This is the first report of plantlet production from anther culture of a Triticeae perennial forage grass. Further experimentation with environmental and cultural conditions may result in the production of green plantlets. PMID- 24241873 TI - Regeneration of plantlets from in vitro cultured cotyledons of white spruce (Picea glauca (Moench) Voss). AB - Adventitious shoot production from seedling cotyledons was investigated for white spruce [Picea glauca (Moench) Voss]. The age of the seedling was found to be important for shoot induction response, the optimum seedling age being 7 to 8 days old. Prior to that age, although response was seen, the multiplication rate was lower. After 7 to 8 days, the capacity to produce shoots declined considerably. The optimum cytokinin (BA) concentration for bud induction was 2 MUM BA. The response to specific BA concentrations was independent of seedling age. The shoot regeneration presented here was highly reproducible and provided primary multiplication rates of approximately 100 to 150 shoots per seedling which had an average of 6 cotyledons. Approximately 30% of 40 regenerated shoots were induced to differentiate roots and all the rooted plantlets were successfully transplanted to soil. PMID- 24241874 TI - Regeneration from long-term cell suspension cultures of tepary bean (Phaseolus acutifolius). AB - Plant regeneration has been achieved from long-term cell suspension cultures established from leaf derived callus of tepary bean (Phaseolus acutifolius). The proportion of densely cytoplasmic cells in suspension culture increased when cultured in the L-6 medium with 54 MUM NAA and 2 MUM KN. Filtration of the cells at each of five consecutive subcultures resulted in the isolation of a plant regenerating cell line (TB 686), which is being maintained in L-6 medium with 4.5 MUM 2,4-D and 2.3 MUM zeatin. Differentiated green cell aggregates were obtained when cells from maintenance medium were transferred to the same medium with 10 MUM BA. Embryo-like structures developed from these aggregates on L-6 medium with 2.3 MUM zeatin, 0.69 MUM GA3 and 1.5 MUM NAA. Plantlets regenerated from these structures when they were cultured on L-6 medium with 7.0 MUM NAA and 1.0 MUM KN. Plant regeneration from the cell line remained relatively constant for 270 days. Regenerated plants were grown to maturity in the greenhouse. PMID- 24241875 TI - The effect of dipicolinic acid on maize tissue culture growth is not solely due to inhibition of lysine biosynthesis. AB - Dipicolinic acid, a known inhibitor of an enzyme (dihydrodipicolinic acid reductase) in the maize (Zea mays L.) lysine biosynthetic pathway, inhibits the growth of maize suspension and callus cultures. Inhibited cultures contain somewhat lower free lysine levels, but the inhibition of suspension culture growth was not reversible with simultaneous addition of L-lysine to the culture medium. It is concluded that dipicolinic acid does not act solely as an analog blocking lysine production. Dipicolinic acid thus appears to be unsuitable as a selection for maize tissue culture mutants with lysine overproduction. PMID- 24241876 TI - The influence of increasing chlorine content on the accumulation and metabolism of polychlorinated biphenyls (PCBs) by Paul's Scarlet Rose cells. AB - Four radiolabled congeners of biphenyls with increasing chlorine content (biphenyl; 1-monochlorobiphenyl; 2,2',4,4'-tetrachlorobiphenyl; and 2,2',4,4',5,5'-hexachlorobiphenyl) were provided to suspension cultures of rose (Rosa sp. cv. Paul's Scarlet) for 4 days. Both the kinetics of (14)C exchange between the cells and medium, and the metabolism of the parent compounds depended on the chlorine content of the congeners. Analysis of both the cells and their medium showed that of the recovered radioactivity 88%, 86%, and 3% of the biphenyl, 1-PCB, and 2,2',4,4'-PCB were metabolized respectively to polar and insoluble residue products. The 2,2',4,4',5,5'-PCB did not appear to be metabolized. PMID- 24241877 TI - Co-electroporation of rice protoplasts with RNAs of cucumber mosaic and tobacco mosaic viruses. AB - Cucumber mosaic virus (CMV) RNA was used to study electroporation conditions suitable for protoplasts from rice suspension cultures. Rice protoplasts required a stronger and shorter electric pulse than tobacco protoplasts for introduction of viral RNA. Under optimized conditions, CMV infection was established in 65 % of electroporated protoplasts. In contrast, electroporation with tobacco mosaic virus (TMV) RNA did not result in infection of rice protoplasts. However, when TMV RNA was electroporated into rice protoplasts together with CMV RNA, TMV production was demonstrated in 15 % of protoplasts. Differential staining with fluorescent antibodies against the two viruses showed that the protoplasts producing TMV were without exception also infected by CMV. The results show that CMV replicates in rice protoplasts by itself, whereas TMV does so only with the aid of CMV. PMID- 24241878 TI - Callus formation and plantlet regeneration from protoplasts derived from suspension cultures of wheat (Triticum aestivum L.). AB - Protoplasts were isolated from anther-derived suspension cultures of commercial wheat (Triticum aestivum L. cv. Chris). The protoplasts were released enzymatically and isolated by centrifugation on a sucrose cushion. The isolated protoplasts were initially cultured in a liquid medium in the dark. Numerous microcalli were produced under these conditions, some of which differentiated into globular embryos. Upon transfer to a solid medium and exposure to 16h/8h light/dark cycle, the protocalli proliferated and many of the somatic embryos matured. Complete plantlets were obtained and maintained in sterile culture. PMID- 24241879 TI - Changes in the integrity of large unilamellar vesicles due to their interaction with tobacco cell suspensions. AB - Negatively charged large unilamellar vesicles (LUV) were incubated with tobacco (Nicotiana tabacum var. xanthi) cell suspensions and with the cell-free medium of the cell suspensions. The extent of cell-LUV interaction was determined by the leakage of the LUV contents. Cells enhanced the leakage of LUV contents and this effect increased with cell age. Addition of polylysine to the reaction mixture increased even further the leakage of the LUV contents. The cell-free medium of the cell suspension also affected the integrity of the LUV. Cell-free medium, by itself, promoted leakage of LUV contents and caused a reduction in the leakage exerted by polylysine. Centrifugation (8000g) of the cell-free medium decreased its effect, heat treatment (122 degrees C) did not alter its effect and sonication enhanced it. The effects of the cell-free medium are attributed to the presence of cell wall debris of disintegrated cells. PMID- 24241880 TI - Sugarcane protoplasts: factors affecting division and plant regeneration. AB - Sugarcane cell suspensions were initiated from leaf callus and sub-cultured every 7 to 10 days by alternate transfer to MS based medium with 3.0 and 1.0 mg 1( 1)2,4-D. Suspensions older than 3 months gave the most reproducible yields of protoplasts. Isolated protoplasts required 50 mM Ca(2+) in the washing solution and 100 mM Ca(2+) in the culture medium to prevent lysis. At plating densities of 2.0-3.0*10(5) ml(-1), 18% or more of the isolated protoplasts produced cell colonies when cultured in droplets or sectors of Kao and Michayluk (1975) based medium with 1.2% w/v Sea Plaque agarose. Cell colonies were of two morphological types. Those consisting of small, tightly packed cells developed into morphogenic callus. The latter produced an abundance of green meristems from which shoots and whole plants were regenerated. PMID- 24241881 TI - Plant regeneration from protoplasts of soybean (Glycine max L.). AB - Protoplasts were isolated from immature cotyledons of six cultivars of Glycine max L. and cultured in the KP8 liquid medium supplemented with 0.2 mg/L 2,4-D, 1 mg/L NAA and 0.5 mg/L ZT. The protoplasts started to divide after 3-5 days of culture. Sustained divisions resulted in mass production of cell colonies and small calli in 6 weeks. The calli further grew to 2-3 mm on the gelritesolidified K8 medium and were transferred onto the MSB medium with 1 mg/L 2,4-D and 0.25 mg/L BA, to obtain compact and nodular calli. Shoot formation was initiated on MSB medium with 0.15 mg/L NAA, and BA, KT and ZT, 0.5 mg/L of each, with or without 500 mg/L CH. It was followed by plant regeneration. So far, 87 plants have been regenerated from 4 cultivars, and normal seeds were obtained from them after transplanting into pots. PMID- 24241882 TI - Measurement of endogenous ABA levels in chilled somatic embryos of carrot by immunoassay. AB - Somatic embryos of carrot, Daucus carota L. 'Royal Chantenay', were chilled at 4 degrees C for the last 3 days of development in order to harden torpedo stage embryos to increase embryo survival during desiccation. ABA levels in chilled and non-chilled embryos were measured using a polyclonal radioimmunoassay and a monoclonal enzyme-linked immunosorbent assay (ELISA). The monoclonal ELISA is the preferred technique due to superior sensitivity and specificity. ABA levels, measured by either technique, were similar in chilled and non-chilled embryos. The relative water content was lower in chilled embryos than in non-chilled embryos and chilling altered protein secretion of one cell line. PMID- 24241883 TI - A new protocol for isolation of mitochondrial DNA from cotton seedlings. AB - A procedure to isolate mtDNA from cotton seedlings G. hirsutum and G. barbadense has been developed. The new protocol allows for the isolation of cotton mtDNA of high purity, yield and digestibility by restriction endonucleases. The success of the protocol is based on critical adjustments in the ionic strength of the homogenizing medium and washing buffer, the speed of grinding during homogenization, and the methods used for lysis of the mitochondria. PMID- 24241884 TI - The relationship of nitrogen source and in vivo nitrate reductase actiity to root formation in Euphorbia esula cell suspension cultures. AB - Root formation and in vivo nitrate reductase (NR) activity were determined in leafy spurge cell suspensions. Cells grown in B5 media with 1 mg L(-1) 2,4-D were transferred to B5 media without 2,4-D, but containing either high (92:8) or low (15:85) ratios of nitrogen as NO 3 (-) -N:NH 4 (+) -N. In older cell lines root formation occurred only in the low NO 3 (-) medium with =<30 roots per flask. In younger cell lines root numbers were greatest in the high NO 3 (-) medium (1000 to 3000 per flask). Cells grown in low NO 3 (-) medium were about one-third the final dry weight as those in high NO 3 (-) medium. Root length was consistently greater for cell lines of all ages in the low NO 3 (-) medium. Developmental profiles of NR activity were similar in cell lines of all ages, whether or not roots were formed. NR activity was lower, however, in cultures grown in low NO 3 (-) medium compared to high NO 3 (-) medium. There was no consistent relationship between NR activity and root initiation. Therefore, nitrate reductase does not appear to be a primary target for regulation of leafy spurge growth by chemical application. PMID- 24241885 TI - Erratum. PMID- 24241886 TI - Passive vapor monitoring of underground storage tanks for leak detection. AB - Passive vapor monitoring of underground storage tanks (USTs) containing volatile hydrocarbons at locations external to the tank (an external system) is touted as a fast and effective method of leak detection. However, major gaps remain in our knowledge of the physical processes that relate a measured vapor concentration to the leak rate, thus making network design according to a quantitative design criterion nearly impossible, and differentiation between surface spills and a leaking UST requires certain levels of sophistication in the leak detection system and in the analysis that are not usually available. Heavier-than-air vapors from the constituents of stored hydrocarbons could result in a density driven convective propagation component that complicates the design of leak detection systems, and finally, detection times are highly sensitive to concentration detection threshold levels set by the system. The use of inadequate systems and analyses can lead to either wasted efforts or excessive subsurface contamination. This paper discusses the physical processes involved, explores the above aspects of external passive vapor leak detection design, and suggests some alternatives as they pertain to gasoline service stations. PMID- 24241887 TI - Fractionation of butyltin species during sample extraction and preparation for analysis. AB - Solvent extraction and evaporative concentration steps are often used in procedures for the measurement of butyltins in environmental samples. As part of a larger study utilizing radiolabeled butyltins, the loss and fractionation of butyltins during sample preparation was investigated. TBT, DBT, and MBT were extracted from acidified seawater by hexane with efficiencies of about 95-99, 50 60 and 11% respectively. In addition, losses of about 70% of DBT were found during evaporative concentration of hexane. A variety of sediment extraction procedures were tested and none were found to be highly efficient for total butyltin extraction. PMID- 24241888 TI - Assessment of airborne fungal spores in different industrial working environments and their importance as health hazards to workers. AB - A survey to assess the occurrence of airborne fungal spores in three different industries, dairies, carpentries and greenhouses, was carried out. The results revealed considerable fungal pollution in the environments of the industries sampled. Noteworthy was the occurrence of fungal genera frequently implicated in allergic and non-allergic diseases, or well known for the production of mycotoxins in foods or characterized by a marked degradative activity on different substrata. Penicillium, Candida, Mucor and Geotrichum were the most common genera identified in the dairies; Penicillium, Cladosporium, yeasts, Trichoderma and Rhizopus occurred more frequently in the carpentries; Cladosporium, Alternaria, Penicillium and Stemphilium were prevailing in the greenhouse.The results of our survey support the idea that, due to their high incidence and variety, fungal spores may represent a potential health hazard in working environments, where their concentration can be affected by many operations and handling. PMID- 24241889 TI - Monitoring air, soil, stream and fish for aerial drift of permethrin. AB - Permethrin drift from two aerial applications at each of two sites in a potato growing area in Ontario were measured to a maximum distance of 61 m outside the treatment area. Droplet drift did not enter the adjacent surface water streams at either study site, since there was little or no wind on the four occasions. The concentration of the insecticide in soil as a result of drifting off site was significantly lower than the amount deposited on the treatment area. The spray drifting off-target was generally made up of droplets <100 MUm. Permethrin residues were detected in the water and sediment samples collected after treatment along the Bailey Creek and Beeton Creek; however, these levels did not cause lethal or sublethal effects to aquatic invertebrates and fish species. Based on the conditions and results of this study, it is concluded that a buffer zone of 65 m around sensitive and productive bodies of water would be effective and practical. PMID- 24241890 TI - Method for evaluating non-economic effects of air pollution. AB - The basic premise underlying the approach presented in the paper is the assumption that humans are unique beings that can evaluate. The environment is described as a system of resources satisfying human needs. The assessment of the effects of environmental pollution derives from the fact that there is, or will be, non-satisfaction of needs resulting from a reduction in environmental resources. PMID- 24241891 TI - A survey of benthic invertebrates in the Suwannee River, Florida. AB - Benthic invertebrate communities were surveyed in a 233 km reach of the middle and lower Suwannee River in Northwestern Florida in the winter 1987 and early summer 1988 to determine their abundance and distribution as potential foods of the Gulf sturgeon, Acipenser oxyrhynchus desotoi, and to determine the effects of possible natural and human-induced disturbances to the communities. In substrates of the tidal oligohaline to mesohaline lower reach of the East Pass site I (km 2) and site II West Pass (km 5) near the Gulf of Mexico, densities of tube dwelling and free swimming amphipods, polychaetes, oligochaetes, and dipterans in the PONAR grabs were moderate (100-999 {iex} individuals/m(2)) to abundant (1000-9999 {iex} individuals m(-2)). Also, at sites I and II, low (10-99 {iex} individuals m(-2)) to moderate densities of dipteran Chironomidae and olive nerite snail were collected in hardboard multiplate artificial substrate samplers. Diversities of benthic invertebrates in both grabs and hardboard multiplates were relatively low. Baetid mayflies were moderately abundant in the dip net samples. Upriver from sites I and II, the transition of an oligohaline tolerant benthic community to a freshwater one was abrupt due to strong freshwater flow. At sites III (km 48) and IV (km 89), benthic invertebrate populations were low to moderate in hardboard multiplate and dip net samples. In the middle reach (km 101 to km 233), aquatic insects were predominant and included; chironomids, mayflies, and beetles, and also, freshwater gammarid amphipods, gastropods, and the Asian clam. In winter, the bottom substrates at sites VII (km 153) and VIII (km 205) contained diverse and dense populations of Chironomidae (5932 m(-2)), the greatest density for a major taxonomic group recorded in this survey. Crayfish were collected in low densities only in artificial substrate samplers from sites IV to IX. Leeches were widespread in the study area. Empirical Biotic Index values that reflect impacts of organic wastes on benthic invertebrate communities were within a narrow range, 3.16 to 6.38, and indicated 'slightly enriched' to 'enriched' water. Of the total 186 benthic invertebrate taxa, 82% had quality values 0 to 5 that indicate overall 'clean water' conditions. The predominant benthic invertebrates in the Suwannee River were detritivorous and the communities reflected oligotrophic to mesotrophic waters. PMID- 24241892 TI - Contaminant exposure of willets feeding in agricultural drainages of the Lower Rio Grande Valley of South Texas. AB - Willets (Catoptrophorus semipalmatus) were collected in June and August 1986 at the outlets of two agricultural drainages into the Lower Laguna Madre of South Texas and at two other Texas coastal sites. Mean liver concentration of arsenic was higher in August than June. Over 20% of the livers had arsenic concentrations elevated above a suggested background level of 5.0 ppm dry weight (DW), but concentrations (maximum 15 ppm) were below those associated with acute toxicity. Selenium concentration in livers varied from 2.3 to 8.3 ppm DW for all locations and represented background levels. Mercury concentrations in livers for all locations (means = 2.0 to 3.4, maximum 17 ppm DW) were below those associated with avian mortality and similar to levels found in other estuarine/marine birds. DDE in carcasses was higher in adults (mean = 1.0 ppm wet weight) than juveniles (0.2 ppm), and higher in August (1.0 ppm) than June (0.5 ppm); however, DDE concentrations were generally at background levels. Based on brain cholinesterase activity, willets were not recently exposed to organophosphate pesticides. PMID- 24241893 TI - Fluorescence-based Broad Dynamic Range Viscosity Probes. AB - We introduce two new fluorescent viscosity probes, SYBR Green (SG) and PicoGreen (PG), that we have studied over a broad range of viscosity and in collagen solutions. In water, both dyes have low quantum yields and excited state lifetimes, while in viscous solvents or in complex with DNA both parameters dramatically (300-1000-fold) increase. We show that in log-log scale the dependence of the dyes' quantum yield vs. viscosity is linear, the slope of which is sensitive to temperature. Application of SG and PG, as a fluorescence-based broad dynamic range viscosity probes, to the life sciences is discussed. PMID- 24241894 TI - Upper extremity transplantation: current concepts and challenges in an emerging field. AB - Loss of an isolated upper limb is an emotionally and physically devastating event that results in significant impairment. Patients who lose both upper extremities experience profound disability that affects nearly every aspect of their lives. While prosthetics and surgery can eventually provide the single limb amputee with a suitable assisting hand, limited utility, minimal haptic feedback, weight, and discomfort are persistent problems with these techniques that contribute to high rates of prosthetic rejection. Moreover, despite ongoing advances in prosthetic technology, bilateral amputees continue to experience high levels of dependency, disability, and distress. Hand and upper extremity transplantation holds several advantages over prosthetic rehabilitation. The missing limb is replaced with one of similar skin color and size. Sensibility, voluntary motor control, and proprioception are restored to a greater degree, and afford better dexterity and function than prosthetics. The main shortcomings of transplantation include the hazards of immunosuppression, the complications of rejection and its treatment, and high cost. Hand and upper limb transplantation represents the most commonly performed surgery in the growing field of Vascularized Composite Allotransplantation (VCA). As upper limb transplantation and VCA have become more widespread, several important challenges and controversies have emerged. These include: refining indications for transplantation, optimizing immunosuppression, establishing reliable criteria for monitoring, diagnosing, and treating rejection, and standardizing outcome measures. This article will summarize the historical background of hand transplantation and review the current literature and concepts surrounding it. PMID- 24241895 TI - Blood pressure-lowering effect of carotid artery stenting in patients with symptomatic carotid artery stenosis. AB - BACKGROUND: In patients with symptomatic carotid artery stenosis, long-term effects of carotid artery stenting (CAS) on blood pressure (BP) changes have not been documented well. We evaluated the effects of CAS on BP and found out its predisposing factors in patients with symptomatic carotid artery stenosis. METHODS: Between January 2003 and June 2012, a total of 107 patients were recruited, and all subjects met the following inclusion criteria: (1) patients underwent CAS with symptomatic carotid artery stenosis > 50%; (2) patients had clinical and radiographic data for at least 1 year of follow-up after CAS; and (3) patients had BP measurements at four different time points: pretreatment, post-treatment, 1-month follow-up, and 1-year follow-up. We evaluated the significance of the BP changes between the pretreatment BP and follow-up BPs, and determined its predisposing factors. RESULTS: Compared to the mean systolic/diastolic BP value (141.0/87.4 mmHg) at the pretreatment BP, the follow up BPs were significantly decreased after CAS (120.5/74.5, 126.2/76.9, and 129.2/79.0 mmHg at the post-treatment, the 1-month follow-up, and the 1-year follow-up, respectively [p < 0.01]). The location of the stenosis (odds ratio = 1.856, 95% confidence interval, 1.388 to 5.589; p = 0.003) and hypertension (odds ratio = 1.627, 95% confidence interval, 1.101 to 3.757; p = 0.014) were independent predisposing factors for BP-lowering effects of CAS on multivariate analysis. CONCLUSIONS: For patients with symptomatic carotid artery stenosis, CAS might have a BP-lowering effect at the 1-year follow-up, especially in patients with hypertension or the stenosis at body lesions. PMID- 24241896 TI - Preparation and diagnostic use of a novel recombinant single-chain antibody against rabies virus glycoprotein. AB - Rabies virus (RABV) causes a fatal infectious disease, but effective protection may be achieved with the use of rabies immunoglobulin and a rabies vaccine. Virus neutralizing antibodies (VNA), which play an important role in the prevention of rabies, are commonly evaluated by the RABV neutralizing test. For determining serum VNA levels or virus titers during the RABV vaccine manufacturing process, reliability of the assay method is highly important and mainly dependent on the diagnostic antibody. Most diagnostic antibodies are monoclonal antibodies (mAbs) made from hybridoma cell lines and are costly and time consuming to prepare. Thus, production of a cost-effective mAb for determining rabies VNA levels or RABV titers is needed. In this report, we describe the prokaryotic production of a RABV-specific single-chain variable fragment (scFv) protein with a His-tag (scFv98H) from a previously constructed plasmid in a bioreactor, including the purification and refolding process as well as the functional testing of the protein. The antigen-specific binding characteristics, affinity, and relative affinity of the purified protein were tested. The scFv98H antibody was compared with a commercial RABV nucleoprotein mAb for assaying the VNA level of anti rabies serum samples from different sources or testing the growth kinetics of RABV strains for vaccine manufactured in China. The results indicated that scFv98H may be used as a novel diagnostic tool to assay VNA levels or virus titers and may be used as an alternative for the diagnostic antibody presently employed for these purposes. PMID- 24241897 TI - Genetic engineering of the complete carotenoid pathway towards enhanced astaxanthin formation in Xanthophyllomyces dendrorhous starting from a high-yield mutant. AB - The yeast Xanthophyllomyces dendrorhous is one of the rare organisms which can synthesize the commercially interesting carotenoid astaxanthin. However, astaxanthin yield in wild-type and also in classical mutants is still too low for an attractive bioprocess. Therefore, we combined classical mutagenesis with genetic engineering of the complete pathway covering improved precursor supply for carotenogenesis, enhanced metabolite flow into the pathway, and efficient conversion of intermediates into the desired end product astaxanthin. We also constructed new transformation plasmids for the stepwise expression of the genes of 3-hydroxymethyl-3-glutaryl coenzyme A reductase, geranylgeranyl pyrophosphate synthase, phytoene synthase/lycopene cyclase, and astaxanthin synthase. Starting from two mutants with a 15-fold higher astaxanthin, we obtained transformants with an additional 6-fold increase in the final step of pathway engineering. Thus, a maximum astaxanthin content of almost 9 mg per g dry weight was reached in shaking cultures. Under optimized fermenter conditions, astaxanthin production with these engineered transformants should be comparable to Haematococcus pluvialis, the leading commercial producer of natural astaxanthin. PMID- 24241898 TI - Part I-mechanism of adaptation: high nitric oxide adapted A549 cells show enhanced DNA damage response and activation of antiapoptotic pathways. AB - Our previous studies demonstrate that A549, a human lung adenocarcinoma line, could be adapted to the free radical nitric oxide (NO([Symbol: see text])). NO([Symbol: see text]) has been shown to be overexpressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serves as a useful model system to study the role of NO([Symbol: see text]) in tumor biology. It is well known that DNA damage response (DDR) is altered in cancer cells and NO([Symbol: see text]) is known to cause DNA damage. Modulations in molecular mechanisms involved in DNA damage response in A549-HNO cells can provide better insights into the enhanced growth behavior of these cells. Thus, here, we carried out a series of time course experiments by treating A549 and A549-HNO cells with NO([Symbol: see text]) donor and examining levels of proteins involved in the DDR pathway. We observed induced expression of key components of DDR pathway in A549-HNO cells. The HNO cells showed sustained expression of key proteins involved in both nonhomologous end joining (NHEJ) and homologous recombination pathways, whereas parent cells only expressed low levels of NHEJ pathway proteins. Further with prolonged NO([Symbol: see text]) exposure, ATR, Chk1, and p53 were activated and upregulated in HNO cells. Activation of p53 results in inhibition of apoptosis through induced Mcl1 expression. It also leads to cell cycle modulation. Interestingly, several reports show that cancer stem cells have enhanced expression of proteins involved in DNA damage response and also activated an antiapoptotic response. Our results here suggest that our HNO adapted A549 cells have increased activation of DNA damage response pathway proteins which can lead to better DNA repair function. Enhanced DDR leads to activation of antiapoptosis response and modulation in the cell cycle which may lead to better survival of these cells under harsh conditions. Thus, our present investigation further supports the hypothesis that HNO exposure leads to survival of these cells. PMID- 24241899 TI - High expressions of galectin-1 and VEGF are associated with poor prognosis in gastric cancer patients. AB - High expressions of galectin-1 and vascular endothelial growth factor (VEGF) are correlated with biological behavior in some cancers. The aim of this study is to evaluate the expressions of galectin-1 and VEGF in gastric cancer and investigate their relationships with clinicopathological factors and prognostic significance. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on 108 cases of gastric cancer. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathological variables, and survival rates was analyzed. Immunohistochemical staining demonstrated that 68 of 108 gastric cancer samples (63.0%) were positive for galectin-1 and 62 out of 108 gastric cancer samples (57.4%) were positive for VEGF. Galectin-1 expression was associated with tumor size, differentiation grade, TNM stage, lymph node metastases, and VEGF expression. VEGF expression was related to tumor size, TNM stage, and lymph node metastases. Kaplan-Meier survival analysis showed that high galectin-1 and VEGF expressions exhibited significant correlations with poor prognosis for gastric cancer patients. Multivariate analysis revealed that galectin-1 and VEGF expressions were independent prognostic parameters for the overall survival rate of gastric cancer patients. The results of the present study suggest that galectin-1 expression is positively associated with VEGF expression. Both galectin-1 and VEGF can serve as independent prognostic indicators of poor survival for gastric cancer. PMID- 24241901 TI - Erroneous perceptions and arousal among regular and occasional video poker players. AB - This study investigated the relationship between the level of arousal (Heart Rate) and the number of erroneous perceptions among video poker players. Twelve regular and twelve occasional gamblers participated in a gambling session conducted in a natural environment. It was hypothesised that 1) a significant positive correlation would be observed between arousal and the number of erroneous verbalizations, 2) regular players would show a higher level of arousal than occasional players, and 3) they would emit more erroneous verbalizations. Results showed that hypotheses one and three were confirmed. Theoretical and practical implications of these results for the psychology of gambling are discussed. PMID- 24241900 TI - An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance. AB - This study aimed to analyze the expression and clinical significance of filamin A (FLNA) in gastric carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 47 cases of gastric cancer and 47 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into gastric cancer SGC-7901 cell line. Reverse transcription-polymerase chain reaction (RT PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3 [4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and migration and invasion assays were also conducted to determine the influence of the upregulated expression of FLNA that might be found on SGC-7901 cell biological effect. Immunohistochemistry: The level of FLNA protein expression was found to be significantly lower in gastric cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of FLNA protein in gastric cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was not correlated with gender, age, and tumor invasion (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function showed that SGC-7901 cell transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with SGC-7901 cell untransfected FLNA (P < 0.05). FLNA expression decreased in gastric cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play important roles as a negative regulator to gastric cancer SGC-7901 cell by promoting degradation of MMP-9. PMID- 24241902 TI - Irrational thinking among slot machine players. AB - According to the cognitive perspective on gambling, regular gamblers persist in trying to win money at gambling because they hold a set of false beliefs about the nature of gambling, the likelihood of winning, and their own expertise. In order to investigate this claim, twenty seven university students were recruited who played one of three types of games at least twice a week: slot machines, video draw poker, and video amusement games. Subjects played their preferred machines on site (clubs, hotels and amusement arcades) first for at least thirty minutes and then the other two games for a minimum of twenty minutes each. During play, each subject spoke aloud into a microphone describing what he or she was doing or thinking about in the game. It was hypothesised that slot machine players would verbalise more irrational thinking than video poker or video amusement players and that slot machines would elicit more irrational thinking than video poker or video amusement machines. Most importantly, it was hypothesised that slot machine players would exhibit relatively greater amounts of irrational thinking when playing their preferred game. The data supported all three hypotheses. Out of all of the statements made by slot machine players when playing slot machines, 38% were categorised irrational. Furthermore, 80% of the strategic statements made by slot machine players while playing slot machines were categorised as irrational. These results are consistent with earlier work which showed high levels of irrational thinking in artificial gambling games. Together, the results provide support for a cognitive view of the origins of gambling problems. PMID- 24241903 TI - Measuring pathological gambling in children: The case of fruit machines in the U.K. AB - The alleged incidence of addiction to fruit machine gambling among children in the U.K. has highlighted the need for a measure to define and count pathological gambling in children. The DSM-IV criteria, which are being refined to diagnose pathological gambling in adults, was adapted for use with pre-adult gamblers. The resulting DSM-IV-J criteria were tested using a questionnaire survey on a sample of 467 schoolchildren aged between 11 and 16 years. Those children who were defined as "probable pathological" gamblers by the DSM-IV-J index were significantly more likely to be involved in behaviours hitherto associated with dependency, than were the control group. DSM-IV-J appears to be a major advance in the discrimination of pathological gambling in children. PMID- 24241904 TI - Risk-taking/gambling-like behavior in preschool children. AB - The types and characteristics of risk-taking or gambling-like behaviors in children are not well understood. Social learning, as one potential etiological factor of risktaking behavior in preschool children, was empirically examined. Prior to playing a risk-taking game, children in the experimental group were exposed to a peer model who had ostensibly won a large prize, whereas control children were exposed to a peer model who had won nothing. Children in the experimental group initiated more risks to win the large prize in the high-risk situation than children in the control group. The results indicated that modeling can enhance risk-taking/gambling-like behavior in young children. Parallels to compulsive gambling in adults, and recommendations for future research were also discussed. PMID- 24241905 TI - Clinical and behavioral evaluation of pathological gambling in Barcelona, Spain. AB - This paper assesses both the clinical characteristics and gambling behavior of 45 pathological gamblers (40 male, 5 female, average age 41) in a psychiatric hospital in Barcelona, Spain. These pathological gamblers tend to have other addictions and psychiatric disorders in addition to their pathological gambling. Suicidal ideation and attempts were one of the most frequent complications with these patients. Slot and fruit machines were found to be the most preferred form of gambling. Loans and crime were frequently used by the gambler to finance his or her gambling. Nevertheless, the gambler is rarely aggessive, and legal problems resulting from serious crimes are the exception. The profile presentes is similar to that found among pathological gamblers in other countries. PMID- 24241906 TI - Comments on "the epistemology of 'addictive disease'". PMID- 24241907 TI - Occupational extremely low-frequency magnetic field exposure and selected cancer outcomes in a prospective Dutch cohort. AB - PURPOSE: To investigate the association between exposure to occupational extremely low-frequency magnetic fields (ELF-MF) and the risk of a priori selected cancer outcomes within the prospective Netherlands Cohort Study. METHODS: 120,852 men and women aged 55-69 years at time of enrollment in 1986 were followed up (17.3 years) for incident lung, breast and brain cancer, and hemato-lymphoproliferative malignancies. Information on occupational history and potential confounders such as sex, age, smoking, alcohol use, and attained educational level were collected at baseline through a self-administered questionnaire. Occupational ELF-MF exposure was assigned with a job-exposure matrix. Using a case-cohort approach, associations with cancer incidence were analyzed with Cox regression stratified by sex, using three exposure metrics: (1) ever had a job with low or high exposure to ELF-MF versus background, (2) duration of exposure, and (3) cumulative exposure. RESULTS: None of the exposure metrics showed an effect on incidence for lung, breast, and brain cancer, nor any of the assessed subtypes in men and women. Of the hemato-lymphoproliferative malignancies in men, ever high exposed to ELF-MF showed a significant association with acute myeloid leukemia (AML) [hazard ratio (HR) 2.15; 95 % confidence interval (CI) 1.06-4.35] and follicular lymphoma (FL) (HR 2.78; 95 % CI 1.00 5.77). Cumulative exposure to ELF-MF showed a significant, positive association with FL but not AML among men. CONCLUSIONS: In this large prospective cohort study, we found some indications of an increased risk of AML and FL among men with occupational ELF-MF exposure. These findings warrant further investigation. PMID- 24241908 TI - A flexible semiparametric transformation model for recurrent event data. AB - In this article, we propose a class of semiparametric transformation models for recurrent event data, in which the baseline mean function is allowed to depend on covariates through an additive model, and some covariate effects are allowed to be time-varying. For inference on the model parameters, estimating equation approaches are developed, and the asymptotic properties of the resulting estimators are established. In addition, a lack-of-fit test is presented to assess the adequacy of the model. The finite sample behavior of the proposed estimators is evaluated through simulation studies, and an application to a bladder cancer study is illustrated. PMID- 24241910 TI - Synthesis of Au-Fe3O4 heterostructured nanoparticles for in vivo computed tomography and magnetic resonance dual model imaging. AB - Water-soluble Au-Fe3O4 heterostructured nanoparticles with high biocompatibility were synthesized and applied as a dual modality contrast agent. These nanoparticles present strong CT/MRI contrast enhancement in a rabbit model. Low concentrations of Au-Fe3O4 were found to obtain a similar effect to high concentrations of a commercial iodine agent in the CT image. PMID- 24241911 TI - A comparison of participation outcome measures and the International Classification of Functioning, Disability and Health Core Sets for traumatic brain injury. AB - OBJECTIVE: To compare the contents of participation outcome measures in traumatic brain injury with the International Classification of Functioning, Disability and Health (ICF) Core Sets for traumatic brain injury. METHOD: A systematic search with an independent review process selected relevant articles to identify outcome measures in participation in traumatic brain injury. Instruments used in two or more studies were linked to the ICF categories, which identified categories in participation for comparison with the ICF Core Sets for traumatic brain injury. RESULTS: Selected articles (n = 101) identified participation instruments used in two or more studies (n = 9): Community Integration Questionnaire, Craig Handicap Assessment and Reporting Technique, Mayo-Portland Adaptability Inventory-4 Participation Index, Sydney Psychosocial Reintegration Scale Version-2, Participation Assessment with Recombined Tool-Objective, Community Integration Measure, Participation Objective Participation Subjective, Community Integration Questionnaire-2, and Quality of Community Integration Questionnaire. Each instrument was linked to 4-35 unique second-level ICF categories, of which 39 100% related to participation. Instruments addressed 86-100% and 50-100% of the participation categories in the Comprehensive and Brief ICF Core Sets for traumatic brain injury, respectively. CONCLUSION: Participation measures in traumatic brain injury were compared with the ICF Core Sets for traumatic brain injury. The ICF Core Sets for traumatic brain injury could contribute to the development and selection of participation measures. PMID- 24241909 TI - Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study. AB - BACKGROUND: In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting. METHODS: Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity. RESULTS: JSLE patients (n = 64; median age 14.1 years) were seen at 3 (interquartile range: 2 5) clinical reviews over 364 (182-532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p < 0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p = 0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p = 0.04) over time. CONCLUSION: Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients. PMID- 24241913 TI - Alarm response by a plethodontid salamander (Desmognathus ochrophaeus): Conspecific and heterospecific "Schreckstoff". AB - The detection of chemical alarm cues plays an important role for predator avoidance in many taxonomic groups, but little is known about the presence of such chemical cues in adult or caudate amphibians. We investigated the response (i.e., aversion or nonaversion) to chemical cues from damaged salamander skin and mealworms (Tenebrio molitor) in the plethodontid salamander,Desmognathus ochrophaeus. Avoidance responses were demonstrated to skin extracts of both conspecific and heterospecific salamanders. However, salamanders (D. ochrophaeus) did not avoid heated conspecific skin, fresh conspecific viscera, fresh mealworm, or freshPlethodon richmondi skin extracts. These results indicate that chemical alarm cues are: (1) present in the skin ofDesmognathus salamanders, (2) not present in mealworm or the viscera ofDesmognathus salamanders, and (3) denatured or deactivated by heating. These results also suggest that an avoidance response to chemical cues from damaged conspecifics has adaptive value in predator avoidance in terrestrial as well as aquatic vertebrates. PMID- 24241912 TI - Thrombin generation and atherosclerosis. AB - Atherosclerosis is a major cause of mortality worldwide. The important role inflammation plays in atherosclerosis is evident through the participation of inflammatory cells in the development and progression of the disease. Thrombin is the central protease of the coagulation cascade, involved in the formation of a hemostatic plug to avoid severe bleeding. In addition, thrombin is a key factor in regulating inflammatory processes, signaling through protease activated receptors. We propose that thrombin may be a relevant factor in the atherosclerosis coagulation-inflammation axis. Human histological data show abundant coagulation activity within atherosclerotic lesions with thrombin activity being related to atherosclerotic plaque development and (in)stability. Animal studies establish that the generated thrombin level relates to progression of atherosclerosis, with hypercoagulability producing advanced atherosclerosis in mice with an Apolipoprotein E-deficient (ApoE(-/-)) background. Several studies show that administration of direct oral anticoagulants, like dabigatran and rivaroxaban, attenuate atherosclerosis development in ApoE(-/-) mice. In this review we explore several mechanisms by which thrombin may operate in modifying the chronic process of atherosclerosis. One of the key elements may be the conversion of thrombin, from a physiological regulator of hemostasis towards an inflammation-mediator under pathophysiological conditions, contributing to a switch in the thrombin-activated protein C (APC) regulation. The ongoing inflammatory activity, indicated by the activation of pro-inflammatory cytokines, neutrophils and neutrophil extracellular traps, drive thrombin generation, while diminishing APC formation. The net result is accelerated pro-inflammatory and pro thrombotic changes in blood and in the vessel wall. We conclude that these atherogenic influences of thrombin may be clinically relevant in the long-term. Further the treatment with long-term anticoagulant therapy deserves further attention as to its potential, vascular side effects. PMID- 24241914 TI - Potential allelochemicals fromRuta graveolens L. and their action on radish seeds. AB - An aqueous extract ofRuta graveolens L. (250 g/liter) was tested for its allelopathic activity in vitro on radish germination and radicle growth in light and darkness. It caused a delay in the onset and a decrease in the rate of germination (40%) in the light. The photoinhibition of germination was accompanied by an inhibition of water uptake into the seed. Furthermore, the inhibition of radicle growth was slightly higher in the light than in darkness. Three potential allelochemicals, biologically active in the light, were isolated from the extract: 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 4 hydroxy-coumarin at concentrations of 10(-4) M, 2*10(-4) M, and 0.4 *10(-5) M respectively. At a concentration of 2*10(-4) M, 5-MOP was the most potent inhibitor, decreasing radish germination to 32% and radicle growth to 17% with respect to control. Microscopic observations of radish seeds treated with 5-MOP suggest that this substance changes the swelling of the seed coat and aleurone layer, which precedes radicle protrusion. PMID- 24241915 TI - Enhanced maize (Zea mays L.) pericarp browning: Associations with insect resistance and involvement of oxidizing enzymes. AB - The kernel pericarp of a maize (Zea mays L.) inbred, Mp313E, that browns rapidly at milk stage when damaged and that is resistant toAspergillus flavus Link and the dusky sap beetleCarpophilus lugubris Murray compared to a susceptible inbred, SC212M, was examined for differing oxidizing enzymes (peroxidases) and their substrate specificity. Additional pericarp enzymes were constitutively produced by the Mp313E inbred compared to the SC212M inbred, as indicated by gel electrophoresis and isoelectric focusing. These enzymes oxidized relevent pericarp substrates such as ferulic acid. Similar results were seen with two varieties of maize containing theCh mutant gene, which brown upon senescence in that enhanced oxidation of ferulic acid was seen in homogenates of browned pericarp compared to that which was cold-shocked and did not brown. Corn powder that was browned by mixing oxidizing enzymes with corn pericarp components ferulic acid and coumaric acid were typically less preferred/more toxic to caterpillars such asHelicoverpa zea (Boddie) and sap beetles such asC. lugubris. Thus, enhanced browning of maize pericarp can promote resistance to insects and is at least partly influenced by the presence of oxidizing enzymes. This mechanism may also promote resistance to maize pathogens, including those that produce mycotoxins. PMID- 24241916 TI - Attraction ofCarpophilus spp. (Coleoptera: Nitidulidae) to synthetic aggregation pheromones and host-related coattractants in Australian stone fruit orchards: Beetle phenology and pheromone dose studies. AB - Synthetic aggregation pheromones ofCarpophilus hemipterus (L.) andCarpophilus mutilatus Erichson were field tested during a 10-month period in southern New South Wales stone fruit orchards to determineCarpophilus spp. phenology and the effect of two pheromone doses on attraction. Aggregation pheromones synergize the attraction of host volatiles toCarpophilus spp. Four major species,C. hemipterus, C. mutilatus, C. davidsoni Dobson andC. (Urophorus) humeralis (F.), were trapped, with greater numbers of each species inC. hemipterus pheromone/fermenting whole wheat breaddough-baited traps, than in dough-only-traps. InC. mutilatus pheromone/ fermenting-dough-baited traps, onlyC. mutilatus andC. davidsoni responded in greater numbers than to dough-only traps. Beetles first appeared in traps in late September (early spring) when daily maximum temperatures averaged 17.5?C. Trappings reached a peak during October and declined to very low levels in November-December (late spring-early summer). Numbers trapped of all species increased during February-March (late summer-early autumn), presumably due to the presence of abundant host resources (ripening and fallen fruit), and continued at high levels until May (late autumn). An 18-week study demonstrated significantly greater responses byCarpophilus spp. to 5000-MUg than to 500-MUg doses of C.hemipterus andC. mutilatus pheromones. Greatest responses to 5000MUg were recorded forC. hemipterus andC. mutilatus responding to their own pheromones (increased attraction over dough alone of 259x and 21.2x respectively). Implications of the study and the potential for using synthetic aggregation pheromones for managingCarpophilus spp. populations in Australian stone fruit are discussed. PMID- 24241917 TI - Effects of benzoic and cinnamic acids on growth, mineral composition, and chlorophyll content of soybean. AB - Organic acids are major water-soluble allelochemicals found in soil infested with quackgrass and are involved in several processes that are important in plant growth and development. This study was carried out to gain more information on the effects of benzoic acid (BEN) andtrans-cinnamic acid (CIN) on growth, mineral composition, and chlorophyll content of soybean [Glycine max (L.) Merr. cv. Maple Bell] grown in nutrient solution. The two allelochemicals reduced root and shoot dry biomass of soybean. Treated plants had fewer lateral roots and tended to grow more horizontally compared to the untreated plants. Lateral roots were stunted and less flexible. The amounts of P, K, Mg, Mn, Cl(-), and SO 4 (2-) were lower, and Zn and Fe contents were higher in roots of plants grown with BEN or CIN as compared to untreated plants. Shoots of plants grown with the allelochemical showed greater accumulation of Ca, Mg, and Zn, whereas P and Fe contents were reduced. The BEN and CIN also caused reductions in leaf chlorophyll content. The BEN and CIN may be responsible for negative allelopathic effects of quackgrass on soybean by inhibiting root growth, by altering ion uptake and transport, and by reducing chlorophyll content. PMID- 24241918 TI - Influence of antifungal compounds from a soil-borne actinomycete onFusarium spp. in asparagus. AB - Asparagus decline syndrome is caused by fungal infection of asparagus roots and crowns byFusarium oxysporum f.sp.asparagi (FOA) andF. moniliforme (FM). Several soil-borne microorganisms have been found inhibitory toFusarium pathogens in other crops. A novelStreptomyces spp. (ME2-27-19A) was isolated from asparagus field soil and found to be inhibitory to FOA and FM in vitro. Solvent extraction of ME2-27-19A and Chromatographic purification of the extract yielded compound(s) that were inhibitory to FOA and FM at 40MUg/ml. ME2-27-19A extract produced variable control of FOA and FM in vitro, and was phytotoxic at 1000 (MUg/ml. In soil, ME2-27-19A extract reduced theFusarium population at 100MUg/ml, but also reduced the asparagus shoot length. PMID- 24241919 TI - Methyl salicylate and (-)-(1R,5S)-myrtenal are plant-derived repellents for black bean aphid,Aphis fabae Scop. (Homoptera: Aphididae). AB - Methyl salicylate and (-)-(1R,5S)-myrtenal stimulate specific olfactory cells in the primary rhinaria on the sixth and fifth antennal segments, respectively, of the black bean aphid.Aphis fabae. In behavioral studies employing a linear track olfactometer, both compounds were repellent toA. fabae and also inhibited attraction to volatiles from its host, broad bean (Vicia faba). Methyl salicylate is associated with secondary metabolite-based defense in plants, and the monoterpenoid (-)-(1R,5S)-myrtenal is metabolically related to (-)-(1S,5S)-alpha pinene, an abundant component of defensive resins produced by gymnosperms. It is argued that these two compounds are employed byA. fabae as indicators of nutritionally unsuitable or nonhost plants. PMID- 24241920 TI - Chemosensory responses of female Asian elephants (Elephas maximus) to cyclohexanone. AB - Cyclohexanone, a naturally occurring component of male Asian elephant temporal gland secretion, was tested as a candidate elicitor of bioresponses from female Asian elephants (Elephas maximus). Four female Asian elephants were presented with synthetic cyclohexanone samples during a standardized bioassay. Four types of bioresponses, some or all of which may be important in intersexual communication, were monitored: flehmen, palatal pit area contact, scrub, and check responses. Cyclohexanone evoked persistent responses of all bioresponse types by two females, moderate response by a third female, and very few responses by a relatively unresponsive female. The results suggest that cyclohexanone may provide chemical information about to females male elephants, particularly regarding their state of musth. PMID- 24241921 TI - Prolonged poststrike elevation in tongue-flicking rate with rapid onset in gila monster,Heloderma suspectum: Relation to diet and foraging and implications for evolution of chemosensory searching. AB - Experimental tests showed that poststrike elevation in tongue-flicking rate (PETF) and strike-induced chemosensory searching (SICS) in the gila monster last longer than reported for any other lizard. Based on analysis of numbers of tongue flicks emitted in 5-min intervals, significant PETF was detected in all intervals up to and including minutes 41-45. Using 10-min intervals, PETF lasted though minutes 46-55. Two of eight individuals continued tongue-flicking throughout the 60 min after biting prey, whereas all individuals ceased tongue-flicking in a control condition after minute 35. The apparent presence of PETF lasting at least an hour in some individuals suggests that there may be important individual differences in duration of PETF. PETF and/or SICS are present in all families of autarchoglossan lizards studied except Cordylidae, the only family lacking linguallly mediated prey chemical discrimination. However, its duration is known to be greater than 2-min only in Helodermatidae and Varanidae, the living representatives of Varanoidea. That prolonged PETF and SICS are typical of snakes provides another character supporting a possible a varanoid ancestry for Serpentes. Analysis of 1-min intervals showed that PETF occurred in the first minute. A review of the literature suggests that a pause in tongue-flicking and delay of searching movements are absent in lizards and the few nonvenomous colubrid snakes tested. The delayed onset of SICS may be a specific adaptation of some viperid snakes to allow potentially dangerous prey to be rendered harmless by venom following voluntary release after envenomation and preceding further physical contact with the prey. PMID- 24241922 TI - Stereochemical inversion of pyrrolizidine alkaloids byMechanitis polymnia (Lepidoptera: Nymphalidae: Ithomiinae): Specificity and evolutionary significance. AB - Pyrrolizidine alkaloids (PAs), acquired by adults or larvae of Danainae and Ithomiinae butterflies and Arctiidae moths from plants, protect these lepidopterans against predators and are biosynthetic precursors of male sex pheromones. The investigation of PAs in many species of wild-caught adults of Ithomiinae showed lycopsamine (1) [(7R)-OH, (2'S)-OH, (3'S)-OH] as the main alkaloid. In incorporation experiments, PA-free (freshly emerged) adults of the ithomiineMechanitis polymnia were fed seven PAs: lycopsamine and four of its known natural stereoisomers-indicine (2) [(7R)-OH, (2'R)-OH, (3'S)-OH], intermedine (3) [(7R)-OH, (2'S)-OH, (3'R)-OH], rinderine (4) [(7S)-OH, (2'S)-OH, (3'R)-OH], and echinatine (5) [(7S)-OH, (2'S)-OH, (3'S)-OH], and two PAs without the 7-OH: supinine (6) [(2'S)-OH, (3'R)-OH] and amabiline (7) [(2'S)-OH, (3'S) OH]. Males epimerized PAs 3, 4, and 5 mainly to lycopsamine (1). Females fed these same three PAs changed a smaller proportion to lycopsamine; their lesser capacity to modify PAs corresponds to their normal acquisition of already transformed PAs from males during mating rather than through visits of adults to plant sources of PAs. The alkaloids1 and2, both 7R and 3'S, were incorporated without or with minimum change by males and females. Feeding experiments with6 and7 (males only) showed an inversion at the 3' center of6 and no change in7. The inversion from 7S to 7R (probably via oxyreduction) may be closely related to the evolution of acquisition of PAs by butterflies and moths. Two hypotheses are discussed: (1) The ancestral butterflies are probably adapted to tolerate, assimilate, and use (7R)-PAs (most common in plants; all widespread 1,2 unsaturated macrocyclic PA diesters show this configuration). The development of (7R)-PA receptors in the butterflies could lead to a specialization on this configuration in two ways: to help find PA plants and to utilize these components in sexual chemical communication. A later appearance of (7S)-PAs in plants could have selected an enzymatic system for the inversion of this chiral center in order to continue producing (7R)-PA-derived pheromones. (2) The inversion would be due to the evolution of a enzyme system specialized in the transport of (7R) PAs to the integument; the failure of this system to carry (7S)-PAs led to an enzymatic system to invert them to transportable (7R)-PAs. In this case, the 7R configuration is an effect and not a cause of (7R)-PA-derived pheromones. In both hypotheses, the partial inversion of the 3'-asymmetric center, when the butterfly was fed intermedine (3), rinderine (4), and supinine (6), could be fortuitous due to the conformation of the molecule and/or the enzymatic system. PMID- 24241923 TI - Interactions betweenAlloxysta brevis (Hymenoptera, Cynipoidea, Alloxystidae) and honeydew-collecting ants: How an aphid hyperparasitoid overcomes ant aggression by chemical defense. AB - Foraging females of the aphid hyperparasitoidAlloxysta brevis were attacked by honeydew-collecting workers of the antLasius niger at the first encounter. However, ants abandoned their attacks quickly, and foragingA. brevis remained unmolested for a subsequent time interval of approximately 5 min, which is long enough for the hyperparasitoid to oviposit successfully. Furthermore, freshly killed intactA. brevis were disregarded by ants, while decapitated specimens were readily removed. We present evidence thatA. brevis females release a mandibular gland secretion, which contains 6-methyl-5-hepten-2-one, actinidin, and unidentified iridoids, in response to an ant attack. This secretion functions both as a measure of self-defense if the female is seized by an ant worker and as a repellent, which prevents ant attacks during subsequent encounters. This is the first evidence for chemical defense in a hymenopterous parasitoid. It enablesA. brevis females to hyperparasitize ant-attended aphids that constitute a major proportion of their hosts and significantly reduces mortality by ectohyperparasitoids. PMID- 24241924 TI - Comparison of walking locomotory reactions of two forms ofCallosobruchus maculatus males subjected to female sex pheromone stimulation (Coleoptera: Bruchidae). AB - A comparison of the walking locomotory reactions of flightless and flight formCallosobruchus maculatus males when subjected to an air current scented with female sex pheromone was undertaken in a tubular olfactometer. The pheromone was delivered to the males either as short pulses or as a continuous flow. To analyze the males' reactions, three behavioral sequences were defined (sequence 1: male sensitivity/arousal; sequence 2: male reactivity; sequence 3; male progression and source location). Although flightless and flight form males were sensitive and reactive in all experiments, their locomotory displacement differed depending on the stimulus conditions. The flightless form males' response remained roughly the same whatever the stimulus conditions (i.e., they always reached the pheromone source). In contrast, the flight form males displayed a markedly reduced response when subjected to a continuous stimulation, indicating that intermittent on-off pheromone stimulation is required in order to sustain their upwind walking progress. This effect could be the result of sensory adaptation and/or habituation in the central nervous system of the flight form, requiring a flickering signal that is unnecessary for the flightless one. PMID- 24241925 TI - Response ofDendroctonus brevicomis Le Conte (Coleoptera: Scolytidae) to different release rates and ratios of aggregation semiochemicals and the inhibitors verbenone and ipsdienol. AB - The response of western pine beetle,Dendroctonus brevicomis Le Conte, to different release rates of the aggregation semiochemicals (attractants)exo brevicomin, frontalin, and myrcene and the inhibitors verbenone and ipsdienol was investigated. Release rates of verbenone ranging from 0.18 mg/ 24 hr to 1.2 mg/24 hr did not result in significant reductions in mean trap catch ofD. brevicomis. In contrast, very low release rates of ipsdienol (0.02-0.4 mg/24 hr) significantly reduced trap catch compared to controls. The combination of verbenone and ipsdienol, released at rates above 0.09 and 0.02 mg/24 hr, respectively, resulted in significantly lower trap catches ofD. brevicomis in attractant-baited traps. Results of an experiment testing a factorial combination of different release rates of verbenone and attractants suggest that response is not ratio-specific. The response curve ofD. brevicomis to the levels of verbenone was similar across all levels of attractants, while the response to equivalent ratios of attractants to verbenone was not similar, suggesting that the behavior of the beetles is primarily influenced by the absolute release rate of verbenone. PMID- 24241926 TI - Glycine max signaling of environmental stress: Dynamics of inducible aromatic allelochemistry. AB - Treatment of Davis soybeans (Glycine max (L.) Merrill) with a proven stress elicitor, iodoacetic acid, which binds specifically with sulfhydryl groups, induced a defensive phytochemistry, which included increased concentrations of aromatic compounds. High-performance liquid chromatography resolved groups of peaks, including one that contains the major allelochemical daidzein and several that contained relatively nonpolar compounds. Some peak groups were increased quantitatively, while others were decreased by iodoacetic acid elicitation. The more significant differences in methanol-extractable HPLC-resolved aromatic metabolites between elicited and nonelicitedG. max apical leaves occurred at 24, 48, and 72 hr after elicitation. PMID- 24241927 TI - Toluene and weasel (2-propylthietane) odors suppress feeding in the rat. AB - The odors of toluene and 2-propylthietane have been shown to elicit fast wave bursts of 15-30 Hz in the olfactory bulb and dentate gyrus of rats. The odors of cadaverine, butyric acid, and caproic acid were found to be ineffective by comparison. The present study investigated feeding in rats offered a choice between food pellets treated with one of the above mentioned odors or untreated pellets. Unscented pellets were also presented in a control condition. The results indicate that 2-propylthietane or toluene scented food is avoided; cadaverine scented food is preferred; but caproic acid and butyric acid scents have no effect. Toluene and 2-propylthietane may activate central pathways involved in predator detection/avoidance, while cadaverine may activate pathways involved in approach and feeding behavior. PMID- 24241928 TI - Effects of host plant,Gossypium hirsutum L., on sexual attraction of cabbage looper moths,Trichoplusia ni (Hubner) (Lepidoptera: Noctuidae). AB - Unmated female or male cabbage looper moths,Trichoplusia ni (Hubner), were attracted more often in a flight tunnel to a cage with moths of the opposite sex and a bouquet of cotton foliage. Increased sexual attractiveness of females with plants may be a result of stimulation of pheromone release in response to plant odor, since more males were attracted when odor of cotton foliage was passed over females than when odor of females was passed over cotton foliage before venting into the flight tunnel. Increased sexual attractiveness of males with plants is due in part to host odor enhancement of female attraction to male pheromone, since more females were attracted to synthetic male pheromone (a blend of enantiomers of linalool and isomers of cresol) and a cotton leaf extract than were attracted to male pheromone alone. A short synthesis procedure was developed for (S)-(+)-linalool, the major component of the male sex pheromone, isolated from hair pencils, used in these tests. PMID- 24241929 TI - Risk-sensitive habitat use by brook stickleback (Culaea inconstans) in areas associated with minnow alarm pheromone. AB - Brook stickleback (Culaea inconstans) share habitat and predators with cyprinid species, and they exploit the alarm pheromone of fathead minnows (Pimephales promelas) to avoid areas of high predation risk. In this field experiment, we measured the retention and duration of area avoidance by brook stickleback from areas marked with alarm pheromone of fathead minnows. Area avoidance was greatest during the first 2 hr after the source of the alarm pheromone was removed (P<0.05), but after 4 hr, area use was not significantly different from premarking levels. This study shows that brook stickleback: (1) use the alarm pheromone of fathead minnows to avoid high risk areas, (2) continue to avoid locations associated with predation risk after the source of the pheromone has gone, and (3) avoid risky areas temporarily, and resume use of risky areas after 2-4 hr. This behavioral response by stickleback to minnow alarm pheromone could serve to minimize risk of predation. PMID- 24241930 TI - Cuticular hydrocarbons wherebyMessor barbarus ant workers putatively discriminate between monogynous and polygynous colonies. Are workers labeled by queens? AB - The results of laboratory experiments carried out with both monogynous and artificially polygynousMessor barbarus ant colonies (which under natural conditions are always monogynous) have shown that the workers belonging to monogynous colonies were able to discriminate between intruders from other monogynous colonies and those from polygynous (di- and trigynous) ones. What mechanisms are involved in this discriminatory ability? Since differences in the relative proportions of the hydrocarbons they carry are known to convey complex messages that are used for recognition purposes, it was proposed here to investigate whether there existed any differences in the proportions of the various hydrocarbons carried by the diverse categories of intruders tested in our experiments. It emerged that one set of hydrocarbons, which were usually present in rather small proportions and included all the families that constitute this species' chemical signature (n-alkanes, mono-, di-, and trimethylalkanes), was characteristically associated with workers from monogynous colonies. Another set of hydrocarbons, which included some of the above components, mostly in larger relative proportions, can be said to have characterized the digynous and trigynous colonies. PMID- 24241931 TI - Comparative analysis of allelopathic effects produced by four forestry species during decomposition process in their soils in Galicia (NW Spain). AB - The development of toxicity produced by vegetable litter of four forest species (Quercus robur L.,Pinus radiata D.Don.,Eucalyptus globulus Labill, andAcacia melanoxylon R.Br.) was studied during the decomposition process in each of the soils where the species were found. The toxicity of the extracts was measured by the effects produced on germination and growth ofLactuca saliva L. var. Great Lakes seeds. The phenolic composition of the leaves of the four species was also studied using high-performance liquid chromatographic analysis (HPLC). It was verified that toxicity was clearly reflected in the first stages of leaf decomposition inE. globulus andA. melanoxylon, due to phytotoxic compounds liberated by their litter. At the end of half a year of decomposition, inhibition due to the vegetable material was not observed, but the soils associated with these two species appeared to be responsible for the toxic effects. On the other hand, the phenolic profiles are quite different among the four species, and greater complexity in the two toxic species (E. globulus andA. melanoxylon) was observed. PMID- 24241932 TI - Inadvertent introduction of squalene, cholesterol, and other skin products into a sample. AB - Recent developments in analytical techniques permit the chemical ecologist to achieve identification of naturally occurring compounds with relatively small amounts of the products of interest. However, the microanalytical techniques employed frequently require the handling of sample vials and other transferral instruments such as syringes and micropipets, where the analyst's hands come into close contact with the sample. Here we show how inadvertent contamination of a sample with skin lipids can occur simply by catching a 1-ml sample vial by the neck rather than the base or by activating a syringe by holding the plunger extension between the fingers rather than taking it by the head. Squalene, cholesterol, and, to a lesser extent, hydrocarbons and fatty acids from fingers are easily introduced into the sample in this manner. These findings are particularly relevant for a parasitology laboratory such as ours, investigating the function of vertebrate-derived products in hematophagous arthropods. PMID- 24241933 TI - Habitat-specific type I polyketide synthases in soils and street sediments. AB - Actinomycetes produce many pharmaceutically useful compounds through type I polyketide biosynthetic pathways. Soil has traditionally been an important source for these actinomycete-derived pharmaceuticals. As the rate of antibiotic discovery has decreased and the incidence of antibiotic resistance has increased, researchers have looked for alternatives to soil for bioprospecting. Street sediment, where actinomycetes make up a larger fraction of the bacterial population than in soil, is one such alternative environment. To determine if these differences in actinomycetal community structure are reflected in type I polyketide synthases (PKSI) distribution, environmental DNA from soils and street sediments was characterized by sequencing amplicons of PKSI-specific PCR primers. Amplicons covered two domains: the last 80 amino acids of the ketosynthase (KS) domain and the first 240 amino acids of the acyltransferase (AT) domain. One hundred and ninety clones from ten contrasting soils from six regions and nine street sediments from six cities were sequenced. Twenty-five clones from two earthworm-affected samples were also sequenced. UniFrac lineage-specific analysis identified two clades that clustered with actinomycetal GenBank matches that were street sediment-specific, one similar to the PKSI segment of the mycobactin siderophore involved in mycobacterial virulence. A clade of soil-specific sequences clustered with GenBank matches from the ambruticin and jerangolid pathways of Sorangium cellulosum. All three of these clades were found in sites >700 km apart. Street sediments are enriched in actinomycetal PKSIs. Non actinomycetal PKSI pathways may be more chemically diverse than actinomycetal PKSIs. Common soil and street sediment PKIs are globally distributed. PMID- 24241934 TI - Purification and characterization of a prolyl endopeptidase isolated from Aspergillus oryzae. AB - A new fungal strain that was isolated from our library was identified as an Aspergillus oryzae and noted to produce a novel proly endopeptidase. The enzyme was isolated, purified, and characterized. The molecular mass of the prolyl endopeptidase was estimated to be 60 kDa by using SDS-PAGE. Further biochemical characterization assays revealed that the enzyme attained optimal activity at pH 4.0 with acid pH stability from 3.0 to 5.0. Its optimum temperature was 30 degrees C and residual activity after 30 min incubation at 55 degrees C was higher than 80 %. The enzyme was activated and stabilized by Ca(2+) but inhibited by EDTA (10 mM) and Cu(2+). The K m and k cat values of the purified enzyme for different length substrates were also evaluated, and the results imply that the enzyme from A. oryzae possesses higher affinity for the larger substrates. Furthermore, this paper demonstrates for the first time that a prolyl endopeptidase purified from A. oryzae is able to hydrolyze intact casein. PMID- 24241936 TI - A statistical model of background air pollution frequency distributions. AB - This paper describes an approach for identifying statistically stable central tendencies in the frequency distributions of time series of observations of background atmospheric pollutants. The data were collected as daily mean values of concentrations of sulfur dioxide and suspended particulate matter at five monitoring stations-three in the USSR, one in Norway, and one in Sweden.The approach uses statistical techniques and methods for constructing multimodal distributions. The problem is subdivided into two parts: first, a decomposition of the observations in order to obtain a description of each season separately and second, an investigation of this description in order to derive statistically stable characteristics of the entire data set. The main hypothesis of the investigation is that dispersion processes interact in such a way that in the zone of influence of one process (near its mode) the 'tails' of the other process are not observed. This permits illumination of interrelations between the physics and the chemistry of the atmosphere. PMID- 24241935 TI - Paliperidone extended-release: safety and tolerability from a metabolic profile perspective. AB - Pharmacologic management strategies for schizophrenia, a relatively common psychotic disorder, include the use of typical and atypical antipsychotic drugs. In general, typical (or conventional) antipsychotics have a proven track record in effectively managing the positive symptoms of schizophrenia but sometimes lack efficacy in treating negative symptoms. The conventional agents are also associated with adverse neurologic effects such as extrapyramidal symptoms (EPS). The development of atypical antipsychotics has partly ameliorated the issue of EPS induced by typical antipsychotics. However, several of these atypical antipsychotic agents have been associated with adverse metabolic effects, including weight gain, dyslipidemia, and increased serum glucose levels. Paliperidone (9-hydroxy-riperidone) extended-release (ER) is an atypical antipsychotic indicated for the treatment of schizophrenia which utilizes a patented oral osmotic system technology that provides constant drug delivery over the course of the day. The efficacy and safety of paliperidone ER in patients with schizophrenia have been established. This review focuses on the metabolic safety of paliperidone ER in patients with schizophrenia. Clinical trials have demonstrated a lack of significant change in lipid profiles with paliperidone ER; furthermore, reported incidences of glucose-related adverse events in clinical trials were very low and similar to those seen with placebo. While dose-related increases in bodyweight of 1-2 kg have been observed with paliperidone ER, there are few reports of clinically relevant increases in bodyweight during treatment. Placebo-controlled trials indicate that the risk of developing metabolic disorders with paliperidone ER is low and similar to that seen with placebo. Furthermore, the ER formulation of paliperidone may offer potential advantages over atypical antipsychotics such as risperidone, particularly with regard to side effects and compliance, but comparative studies are needed. PMID- 24241937 TI - Cadmium and lead in common terns (Aves: Sterna hirundo): Relationship between levels in parents and eggs. AB - We analyzed cadmium and lead levels in feathers of mated pairs of common terns (Sterna hirundo) and in their eggs to determine if metal levels in eggs correlated with female levels, and whether there were intrapair and intermetal correlations. Eggs had significantly lower lead levels (89 ng g(-1)) and cadmium levels (4.0 ng g(-1)) than adult feathers (500 and 50 ng g(-1) respectively). Adult females had higher metal levels than males. Cadmium and lead levels were correlated across families for females, males and eggs. Lead, but not cadmium, levels were correlated in females and their eggs. PMID- 24241938 TI - Trace metals in the bottom sediments of the harbour of Lagos, Nigeria. AB - A study has been made of the heavy metal contents of sediments in the harbour of Lagos which receives a variety of human and industrial wastes. The results indicate three areas with low, medium and high pollution by heavy metals. The harbour in which most shipping activities are concentrated has a low level of pollution. Both other areas with medium and high pollution by heavy metals are located at the entrance and in northwest sections of the harbour respectively, which receive effluents from industries and communities. PMID- 24241939 TI - Lichen biomonitoring of mercury emission and deposition in mining, geothermal and volcanic areas of Italy. AB - Natural emissions of Hg are attracting increased interest both for their environmental implications and for possible applications in the exploration of mineral, petroleum and geothermal fields. However, daily and seasonal fluctuations in concentrations of Hg in the atmosphere, caused by meteorological and environmental variables, has made it very difficult to assess Hg anomalies by conventional analytical procedures. Some species of widespread foliose lichens from an abandoned cinnabar mining and smelting area (Mt. Amiata), geothermal fields (Larderello, Bagnore and Piancastagnaio, Central Italy), and active volcanic areas (Mt. Etna and Vulcano, Southern Italy) seem to be very suitable biomonitors of gaseous Hg; especially as lichen thalli have an Hg content which reflects average values measured in air samples. We discuss the advantages of quantitative biological monitoring by lichens with respect to conventional air sampling in large-scale monitoring. PMID- 24241940 TI - Contaminants in American alligator eggs from Lake Apopka, Lake Griffin, and Lake Okeechobee, Florida. AB - Residues of organochlorine pesticides, polychlorinated biphenyls (PCBs), and 16 elements were measured in American alligator (Alligator mississippiensis) eggs collected in 1984 from Lakes Apopka, Griffin, and Okeechobee in central and south Florida. Organochlorine pesticides were highest in eggs from Lake Apopka. None of the elements appeared to be present at harmful concentrations in eggs from any of the lakes. A larger sample of eggs was collected in 1985, but only from Lakes Griffin, a lake where eggs were relatively clean, and Apopka, where eggs were most contaminated. In 1985, hatching success of artificially incubated eggs was lower for Lake Apopka, and several organochlorine pesticides were higher than in eggs from Lake Griffin. However, within Lake Apopka, higher levels of pesticides in chemically analyzed eggs were not associated with reduced hatching success of the remaining eggs in the clutch. Therefore, it did not appear that any of the pesticides we measured were responsible for the reduced hatching success of Lake Apopka eggs. PMID- 24241941 TI - River evaluation using ecotoxicological and microbiological procedures. AB - One of the many problems researchers and managers face is to try and interpret data collected from various river studies. There is an underlying awareness of the incompleteness of most data bases due to a variety of problems outside of those concerning sample processing.In this study we have attempted, by using the battery of tests approach (12 tests) and the examination of different types of samples such as water, Milli-Q water extracted sediments, and organic solvent extracted sediments, to explore the implication of spacial and temporal sampling programmes.The results obtained were not unexpected: there were spatial and temporal influences, sometimes so great that it would appear that you were examining samples from different parts of the country. However, data arising from solvent extracted sediments were found to be much less influenced by temporal sampling than by spatial variation. Another interesting and important observation was that sediment composition appeared to have no relationship to toxicant content.In this study, the first field application of the Mutatox test (genotoxicity) was carried out and it was found to be a very responsive test in all three types of samples. This test shows great promise as laboratory studies indicate it is sensitive to many of the chemicals which trigger the Ames test. PMID- 24241942 TI - Introductory comments. PMID- 24241943 TI - Seeing the baby: The impact of ultrasound technology. AB - This paper reports results of a study of prenatal diagnosis patients who underwent ultrasound examinations and lost their pregnancies through miscarriage or elective terminations. The majority of the women felt that viewing the ultrasound image influenced their relationship to the fetus and their coping with the pregnancy loss. The women commented on the power of ultrasound to make their pregnancies more real as well as the painful yet sometimes beneficial consequences of seeing the fetus. Clinical implications are considered for health professionals who provide prenatal diagnostic services or counseling after pregnancy loss. PMID- 24241944 TI - Letter to a genetic counselor. AB - The author describes her personal experience terminating a pregnancy after receiving an abnormal amniocentesis result: While still waiting for the results, she and her husband attempted to deny the importance of the pregnancy, an approach which they subsequently regretted. When they received the abnormal result, they found themselves able to make necessary decisions quickly, despite being in shock. It then took some time before they realized what a major loss they had actually suffered. The painful aftermath included accepting emotional responsibility for their decision to abort, as well as explaining that difficult decision to their older children. Thoughts of a possible subsequent pregnancy could not be faced at once. Over time, the author found the support of friends and colleagues, and even of a support group, to be invaluable. All in all, the entire experience was more painful than she would have predicted, and she hopes that this account will prove helpful both to genetic counselors and to other patients who receive abnormal results from prenatal diagnosis. A list of suggested readings is appended. PMID- 24241946 TI - Abstracts of papers presented at the Tenth Annual NSGC Educational Conference: The interface between public health and clinical genetics. PMID- 24241945 TI - The future of genetics in public health. AB - During the 1980s, we have witnessed an erosion in federal and state funding for the coordination of genetic services in state health departments. As this decade begins, the federal budget for the support of the national genetics program is less than half of the total available in 1980. In addition, priorities in state maternal and child health programs have changed, and genetic services have often received lower rankings aside of programs to improve prenatal care and to address problems such as teenage pregnancy. Clearly we are at a critical point for the future of genetics programs in the public health arena. Fortunately, despite the problems with funding and priority setting, important coalitions have been built during the past decade and continued advances in medical genetics have made it difficult for public health officials to ignore the potential impact of genetic services. Council of Regional Networks for Genetic Services (CORN) and the regional genetic services networks have provided opportunities for interaction and coordination between genetic services providers and public health officials that had not been available to any significant extent. The full potential of these coalitions has yet to be realized, but efforts in data collection, development of national guidelines and standards, and information sharing and networking have already had an influence on state genetic services programs. Continuing research on the genetics of chronic diseases and the influence of discoveries in molecular genetics will undoubtedly broaden the current scope of state public health programs in genetics, which all too often have been limited to newborn screening and administration of grants for genetic services. The regional and national genetic services programs should be strengthened and appropriate training programs should be developed in Schools of Public Health to provide the expertise and leadership that will be needed to guide the future of genetics in public health. PMID- 24241947 TI - Duration of viraemia in Chinese acute sporadic hepatitis E. AB - Acute sporadic hepatitis E (ASHE) cases induced by hepatitis E virus genotype 4 (HEV-4) are increasing in China. Our study aimed to estimate the duration of HEV 4 viraemia in Chinese ASHE. A total of 619 serum specimens from 499 ASHE patients were examined for the presence of HEV RNA. The association between viraemia detection and serum sampling time was compared between subtypes. The cumulative probability of HEV viraemia detection was determined using Kaplan-Meier survival analysis, and the viraemia duration was estimated. A total of 42.7 % of serum specimens were positive for HEV RNA and all the isolated strains were identified as genotype 4 and subsequently assigned to five subtypes. Among the patients infected with subtypes 4d and 4i, the time interval from the initiation of clinical symptoms to serum specimen sampling was shorter than that among the patients with subtypes 4a, 4b and 4h. Kaplan-Meier analysis was conducted with 101 sequential specimens as well as with both 101 sequential specimens and 236 single negative specimens. The cumulative probability of HEV-4 viraemia detection was estimated to decline quickly to approximately 10 % within 32 days after the initiation of clinical symptoms and then to decline very slowly to 5 % by the 41st day and to zero by the 131st day. The majority of ASHE cases maintain detectable HEV-4 viraemia within one month after onset, whereas a small portion of cases maintain long-term viraemia and may act as a reservoir for further transmission. PMID- 24241948 TI - When psychiatric diagnosis becomes an overworked tool. AB - A psychiatric diagnosis today is asked to serve many functions-clinical, research, medicolegal, delimiting insurance coverage, service planning, defining eligibility for state benefits (eg, for unemployment or disability), as well as providing rallying points for pressure groups and charities. These contexts require different notions of diagnosis to tackle the particular problem such a designation is meant to solve. In a number of instances, a 'status' definition (ie, a diagnostic label or category) is employed to tackle what is more appropriately seen as requiring a 'functional' approach (ie, how well the person is able to meet the demands of a test of performance requiring certain capabilities, aptitudes or skills). In these instances, a diagnosis may play only a subsidiary role. Some examples are discussed: the criteria for involuntary treatment; the determination of criminal responsibility; and, assessing entitlements to state benefits. I suggest that the distinction between 'status' versus 'function' has not been given sufficient weight in discussions of diagnosis. It is in the functional domain that some of the problematic relationships between clinical psychiatry and the social institutions with which it rubs shoulders are played out. A status, signified by a diagnosis, has often been encumbered with demands for which it is poorly equipped. It is a reductive way of solving problems of management, allocation or disposal for which a functional approach should be given greater weight. PMID- 24241949 TI - [Minimal-invasive microwave coagulation therapy for liver tumours: laparoscopic and percutaneous access]. AB - INTRODUCTION: Local ablative treatments play an important role in current surgical treatment strategies. Radiofrequency ablation (RFA) as one of the most popular examples suffers from partly inacceptable local tumour control. Microwave coagulation therapy (MCT) is a comparatively new type of ablation promising several improvements. This series is to the best of our knowledge the first within the central European area, which reports on the successful clinical implementation of MCT in a surgical department. PATIENTS AND MATERIALS: A novel 915 MHz system (MedWavesTM, AveCure Inc., SanDiego, CA/U. S. A.) was used to treat 47 patients with 80 tumour nodules in 51 treatment sessions. Average tumour size was 2.6 +/- 0.9 cm. Indications were hepatocellular carcinoma in 29 patients and metastases in 14 as well as 4 cholangiocellular carcinomas. The approach was laparoscopic (20) or percutaneous (31). High-risk conditions defined by unfavourable tumour localisation like invisibility in native transabdominal ultrasound, superficial tumour site or risk of heat sink phenomena were found in 28 cases (53 %). RESULTS: Local recurrence rate was 17 % on a per-patient and 12 % on a per-tumour basis (n = 9). One patient died because of incurable upper gastrointestinal bleeding during the postoperative hospital stay. No MCT associated complication occurred. Median follow-up period was 20 months. Local tumour recurrence was significantly different on comparing laparoscopic to percutaneous MCT (p = 0.032, chi2 test), as was global recurrence (p = 0.011, chi2 test). In a univariate logistic Cox regression, tumour size, access and high risk localisation were significant prognostic factors for local tumour recurrence, however, in a multivariate reiteration, only the chosen access to MCT (p = 0.012) and tumour size (p = 0.044) remain significant. CONCLUSION: MCT seems to be a useful tool, easy to implement in a surgical environment and may eventually prove to be superior to other local ablative treatment modalities. Even unfavourable tumour localisations could be treated safely and efficiently using MCT without increased risk of local tumour recurrence. PMID- 24241950 TI - [Incidence of Candidaemia Following Abdominal Surgery in German Hospitals]. AB - BACKGROUND: Invasive Candida infections following abdominal surgery represent a significant medical problem. This study initiates a benchmarking project to pinpoint the current role and epidemiology of candidemia in this patient group in German hospitals. MATERIAL AND METHODS: During the year 2010 data derived from 47 704 abdominal surgery cases in hospitals from Germany were analysed in order to determine benchmarking incidences for candidemia. RESULTS AND CONCLUSION: In 20.3 % of all recognised bloodstream infections Candida spp. were identified as the responsible organisms. If related to all abdominal surgery cases analysed in this study, a candidemia-benchmarking incidence of 0.15 % (95 % CI: 0.10-0.21 %) was determined. In patients who required intensive care after surgery the incidence of candidemia was found to be 0.89 % (95 % CI: 0.57-1.38 %). The incidence increased to 3.13 % (95 % CI: 2.09-4.66 %) in patients who received blood culture diagnosis. The German National Reference Centre of Systemic Mycosis provides hospital specific data for participants of this study to enable benchmarking and infection control (www.nrz-mykosen.de/gastrointestinalchirurgie). PMID- 24241951 TI - [Prof. H. J. Meyer - new General Secretary of the German Society of Surgery]. PMID- 24241952 TI - [Liver Transplantation as Treatment for Rare Diseases in Adults]. AB - In addition to the main indications pertaining to 95 % of all patients receiving liver transplantation in Germany, there are numerous other diseases that may become clinically evident in the adult age and may lead to the decision for liver transplantation. These may be metabolic diseases with their main defect located in the liver, malformations of liver cells, hepatic vascular diseases and rare tumours of the liver. Standard exceptions for the listing are in place only for a limited number of diseases. Exact diagnostics and the point in time for transplantation are crucial for the prognosis. PMID- 24241953 TI - [Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology]. AB - Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options. PMID- 24241954 TI - [Intraductal papillary mucinous neoplasm of the pancreas (IPMN)--standards and new aspects]. AB - Intraductal papillary mucinous neoplasms (IPMN) of the pancreas belong to the heterogeneous group of cystic pancreatic lesions and have been diagnosed more frequently in recent years. Diagnosis and differentiation from other cystic lesions (pseudocysts, serous-cystic neoplasias [SCN], mucinous-cystic neoplasias [MCN], intraductal papillary-mucinous neoplasias [IPMN] and solid pseudopapillary neoplasias [SPN]) is often challenging. IPMN of the pancreas are considered as precursor lesions for the development of invasive pancreatic cancer. However, depending on the morphological (MD-IPMN, BD-IPMN) and histological subtype (intestinal, pancreatobiliary, oncocytic or gastric) the malignant potential of IPMNs varies significantly. Hence, early diagnosis and selection of the appropriate therapeutic strategy is necessary for optimal outcome and cure. There is a strong consensus for the resection of all MD-IPMN. Small BD-IPMN without signs of malignancy can be followed by observation. The increasing understanding of the histopathology and tumour biology of IPMN has led to an amendment of the 2006 International Association of Pancreatology (IAP) guidelines for the treatment of cystic pancreatic tumours. In consideration of recent data, recommendations for observation and/or follow-up of IPMN cannot be given definitely. PMID- 24241955 TI - [Alterations of vertebrocerebral arterial branches in children and adolescents - current aspects of epidemiology, diagnostics, treatment, outcome and follow-up including a representative case report]. AB - INTRODUCTION: Vascular alterations such as arterial lesions themselves or caused by injuries (external site) occur only rarely in children and adolescents. By means of a narrative review including our own clinical experience and a representative case report, vascular alterations in children and adolescents are discussed. Complex Patient- & clinical Finding-associated Aspects: - Dissections of vertebrocerebral arterial branches: usually, the aetiopathogenesis reveals external factors or primary alterations of the vascular wall. The therapeutic approach comprises anticoagulation or surgical, sometimes endovascular intervention in cases of recurrent ischaemic symptoms. - Aneurysm of the carotid artery: the therapeutic approach is characterised by surgical and interventional treatment according to the individual case-specific finding, alternatives in vascular reconstruction can be derived from the classification by de Jong et al. Representative Case Report: An 11 year old boy was diagnosed with intracranial dissection of the left vertebral artery initially treated with anticoagulation (6 months) and a consecutive neurosurgical approach (trepanation and coverage of the dissecting aneurysm) and, subsequently (within the 16th year of age), he underwent interventional treatment (coil embolisation) because of an expansion of the aneurysm. In addition, an aneurysm of the right internal carotid artery was found, which was approached surgically with interposition of a vena-saphena-magna segment. CONCLUSION: Vascular alterations such as dissections and aneurysms of vertebrocerebral arterial branches in children and adolescents are challenging. Dissections should be treated with anticoagulation. In the case of recurrent ischaemic symptoms or in cases of pressure phenomenon including neurological alterations, interventional or surgical treatment is indicated. In the case of an aneurysm of the carotid artery, there is an indication for surgical treatment: In children and teenagers, venous segments for interposition and single-stitch sutures are usually used. Competent decision-making for treatment and periinterventional management require appropriate interdisciplinary expertise. PMID- 24241956 TI - Basal cardiac autonomic tone is normal in patients with periodic leg movements during sleep. AB - The relationship between the autonomic nervous system and periodic leg movements during sleep (PLMS) is not completely understood. We aimed to determine whether patients with PLMS exhibit any changes in their basal heart rate variability (HRV), excluding episodes of leg movements and arousals. To investigate this, we conducted a cross-sectional study including 13 patients with PLMS (PLMS >= 20) and 13 matched controls, free of cardiovascular diseases and medications. Time and frequency-domain HRV measures [mean R-R interval, low frequency (LF), high frequency (HF), LF/HF] were calculated across all sleep stages as well during wakefulness just before and after sleep during one-night polysomnography. We only took ECG segments of sleep without arousals and excluded periods of 30 s before and after the leg movements. No statistical differences between PLMS and control subjects were found in any of the time- or frequency-domain HRV measures across sleep stages. Basal cardiac autonomic modulation in patients with PLMS is similar to that of control subjects. Our results argue against a role for a basal disturbance of the cardiac autonomic nervous system in the pathogenesis of PLMS. PMID- 24241957 TI - Quality of home-based rapid HIV testing by community lay counsellors in a rural district of South Africa. AB - INTRODUCTION: Lack of universal, annual testing for human immunodeficiency virus (HIV) in health facilities suggests that expansion of HIV testing and counselling (HTC) to non-clinical settings is critical to the achievement of national goals for prevention, care and treatment. Consideration should be given to the ability of lay counsellors to perform home-based HTC in community settings. METHODS: We implemented a community cluster randomized controlled trial of home-based HTC in Sisonke District, South Africa. Trained lay counsellors conducted door-to-door HIV testing using the same rapid tests used by the local health department at the time of the study (SD Bioline and Sensa). To monitor testing quality and counsellor skill, additional dry blood spots were taken and sent for laboratory based enzyme-linked immunosorbent assay (ELISA) testing. Sensitivity and specificity were calculated using the laboratory result as the gold standard. RESULTS AND DISCUSSION: From 3986 samples, the counsellor and laboratory results matched in all but 23 cases. In 18 cases, the counsellor judged the result as indeterminate, whereas the laboratory judged 10 positive, eight negative and three indeterminate, indicating that the counsellor may have erred on the side of caution. Sensitivity was 98.0% (95% CI: 96.3-98.9%), and specificity 99.6% (95% CI: 99.4-99.7%), for the lay counsellor field-based rapid tests. Both measures are high, and the lower confidence bound for specificity meets the international standard for assessing HIV rapid tests. CONCLUSIONS: These findings indicate that adequately trained lay counsellors are capable of safely conducting high-quality rapid HIV tests and interpreting the results as per the kit guidelines. These findings are important given the likely expansion of community and home-based testing models and the shortage of clinically trained professional staff. PMID- 24241958 TI - The role of CRE1 in nucleosome positioning within the cbh1 promoter and coding regions of Trichoderma reesei. AB - Nucleosome positioning within the promoter and coding regions of the cellobiohydrolase-encoding cbh1 gene of Trichoderma reesei was investigated. T. reesei is a filamentous fungus that is able to degrade dead plant biomass by secreting enzymes such as cellulases, a feature which is exploited in industrial applications. In the presence of different carbon sources, regulation of one of these cellulase-encoding genes, cbh1, is mediated by various transcription factors including CRE1. Deletion or mutation of cre1 caused an increase in cbh1 transcript levels under repressing conditions. CRE1 was shown to bind to several consensus recognition sequences in the cbh1 promoter region in vitro. Under repressing conditions (glucose), the cbh1 promoter and coding regions are occupied by several positioned nucleosomes. Transcription of cbh1 in the presence of the inducer sophorose resulted in a loss of nucleosomes from the coding region and in the re-positioning of the promoter nucleosomes which prevents CRE1 from binding to its recognition sites within the promoter region. Strains expressing a non-functional CRE1 (in strains with mutated CRE1 or cre1-deletion) exhibited a loss of positioned nucleosomes within the cbh1 coding region under repressing conditions only. This indicates that CRE1 is important for correct nucleosome positioning within the cbh1 coding region under repressing conditions. PMID- 24241959 TI - Part II-mechanism of adaptation: A549 cells adapt to high concentration of nitric oxide through bypass of cell cycle checkpoints. AB - Previous work has shown enhanced survival capacity in high nitric oxide (HNO) adapted tumor cells. In Part I of this series of manuscripts, we have shown that A549-HNO cells demonstrate an improved growth profile under UV and X-ray radiation treatment. These cells exhibit increased expression of proteins involved in DNA damage recognition and repair pathway, both the non-homologous end joining pathway and homologous recombination. These include Ku80, DNA-PK, XLF ligase and MRN complex proteins. Further, the A549-HNO cells show high levels of ATM, ATR, Chk1 and Chk2, and phospho-p53. Activation of these molecules may lead to cell cycle arrest and apoptosis due to DNA damage. This is observed in parent A549 cells in response to NO donor treatment; however, the A549-HNO cells proliferate and inhibit apoptosis. Cell cycle analysis showed slowed progression through S phase which will allow time for DNA repair. Thus, to better understand the increased growth rate in A549-HNO when compared to the parent cell line A549, we studied molecular mechanisms involved in cell cycle regulation in A549-HNO cells. During the initial time period of NO donor treatment, we observe high levels of cyclin/Cdk complexes involved in regulating various stages of the cell cycle. This would lead to bypass of G1-S and G2-M checkpoints. The HNO cells also show much higher expression of Cdc25A. Cdc25A activates Cdk molecules involved in different phases of the cell cycle. In addition, there is enhanced phosphorylation of the Rb protein in HNO cells. This leads to inactivation of Rb/E2F checkpoint regulating G1-S transition. This may lead to faster progression in S phase. Thus, all of these perturbations in HNO cells lead to accelerated cell cycle progression and a higher growth rate. We also assessed expression of cell cycle inhibitors in HNO cells. Interestingly, the HNO cells show a significant decline in p21CIP1 at initial time points, but with prolonged exposure, the levels were much higher than those of the parent cells. This suggests an initial bypass of cell cycle checkpoints as p21CIP1 can inhibit the activity of all cyclin/Cdk complexes. p21CIP1 is also known to inhibit p53 induced apoptosis. This could be important during later phases of the cell cycle to allow time for repair of damaged DNA and thus better survival of HNO cells. PMID- 24241960 TI - Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer. AB - Tumor markers Ki67, TP53, and TP63 are common labels in the diagnosis of bladder cancer (BCa) around the world. The combination of those biomarkers may have advantages in predicting BCa prognosis and non-muscle-invasive bladder cancer (NMIBC) postoperative recurrence. We investigated the immunohistochemical profiles of 313 bladder cancer samples classified under the WHO/ISUP (2004) grading scale and the UICC-TNM (2002) classification. Then we investigated their predictive value in the tumor recurrence of 270 NMIBC patients after TURBT. Expression of Ki67 correlates with grade, stage, tumor size, and tumor numbers. Semiquantitative evaluation of TP53 correlates with grade and invasive conditions. The positive expression rate of TP63 correlated with tumor grade and stage. The combined effect of TP53 and Ki67 revealed a predictive value in NMIBC recurrence. However, the positive TP63 expression did not show any protective effect in NMIBC recurrence. The expression of TP53 and Ki67 could be used to predict the risk of NMIBC recurrence postoperatively. PMID- 24241961 TI - Comment on: Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma metastasis. Gao L, Liu J, Zhang B, Zhang H, Wang D, Zhang T, Liu Y, Wang C. Tumour Biol. 2013, in press. AB - Gao and collaborators (Tumour Biol, 2013) have investigated the role of mucin 4 (MUC4) in lung cancer and have concluded that a loss of MUC4 results in epithelial mesenchymal transition via beta-catenin nuclear translocation and that MUC4 expression is correlated with a risk of lymph node metastasis in a cohort of 20 lung adenocarcinoma patients. This surprising analysis is contradictory to most of the scientific knowledge and literature regarding MUC4 contribution in epithelial cancers that is very hardly discussed in their manuscript. PMID- 24241963 TI - Of Gdansk and glass houses. PMID- 24241962 TI - Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy. AB - High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54 19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction. PMID- 24241964 TI - Does chronic kidney disease affect outcomes after major abdominal surgery? Results from the National Surgical Quality Improvement Program. AB - INTRODUCTION: The impact of chronic kidney disease (CKD) and end-stage renal disease on outcomes following major abdominal surgery is not well defined. MATERIALS AND METHODS: The 2008 NSQIP database was queried to identify adult patients undergoing complex abdominal surgery (major colorectal, hepatobiliary, pancreatic, gastric, and esophageal operations). Thirty-day morbidity and mortality in patients on hemodialysis (HD) versus patients not on HD were compared. The impact of preoperative renal insufficiency, measured by glomerular filtration rate (GFR), on morbidity and mortality was then assessed in non dialysis patients. RESULTS: Of 24,572 patients who underwent major abdominal operations, excluding emergency cases, only 149 (0.6%) were on HD preoperatively. Thirty-day mortality in the HD group was 12.8% compared to 1.8% for those not on HD (p < 0.0001). Overall complication rate was 23.5 versus 12.3% (p < 0.0001). In particular, rates of pneumonia (6.7 vs 3.0%, p < 0.05) and sepsis (12.8 vs 5.3%, p < 0.001) were higher in patients on HD. In patients not on HD, GFR was significantly predictive of postoperative mortality after controlling for age, gender, race, emergency status, and comorbidities. Compared to patients with normal preoperative kidney function (GFR, 75-90 ml/min/1.73 m(2)), even modest CKD (GFR, 45-60 ml/min/1.73 m(2)) was associated with increased postoperative mortality (odds ratio (OR), 1.62). With greater impairment in kidney function, postoperative mortality was even more marked (GFR, 30-45 ml/min/1.73 m(2) and OR, 2.84; GFR, 15-30 ml/min/1.73 m(2) and OR, 5.56). In addition, CKD was independently associated with increased postoperative complications. CONCLUSION: Any degree of preoperative kidney impairment, even mild asymptomatic disease, is associated with clinically significant increases in 30-day postoperative morbidity and mortality following major abdominal surgery. PMID- 24241965 TI - Factors predicting long-term survival following pancreatic resection for ductal adenocarcinoma of the pancreas: 40 years of experience. AB - BACKGROUND: Long-term survival after resection for pancreas carcinoma has rarely been reported. Factors influencing long-term survival are still under debate. The aim of this study was to define predictors for long-term survival. METHODS: Between 1972 and 2004, a total of 415 patients underwent resection. Data were collected in a prospective data base. Data of 360 patients were available for further analysis in 2011. All specimens of long-term survivors were histologically reviewed. RESULTS: Long-term survivors (n = 69) had a median survival of 91 months. Pathological re-evaluation of all specimens re-confirmed the diagnosis. Predictive factors for long-term survival in univariate analysis were no preoperative biliary stent, low CA 19-9 level, lack of blood transfusion, R0 resection, tumour diameter, and -grading, absence of lymph node or distant metastases, lymphangiosis, and perineural infiltration. Adjuvant chemotherapy showed a significant influence on overall survival but not on long-term survival. In multivariate analysis, lymph node ratio and volume of blood transfusion were predictors of long-term survival. CONCLUSION: Nearly 20% of patients with pancreas carcinoma who undergo surgical resection have a chance of long-term survival. Survival beyond 5 years is predicted by clinical and tumour-specific factors. Adjuvant chemotherapy might prolong overall survival but is, according to these results, unable to contribute to long-term survival. There is still a risk of recurrence after a 5- or even a 12-year mark. Survival beyond 5 or even 12 years, therefore, does not assure cure. PMID- 24241966 TI - Impact of thoracic recurrent laryngeal node dissection: 508 patients with tri incisional esophagectomy. AB - BACKGROUND: To evaluate the feasibility and safety of recurrent laryngeal nerve (RLN) lymph node (LN) dissection, this study compared the postoperative complications and survival between modern two-field lymphadenectomy (MTL) and modified standard two-field lymphadenectomy (MSTL) by using the propensity score matching method. METHODS: After generating propensity scores given the covariates of age, sex, tumor length, tumor location, tumor grade, and clinical stage, 254 patients with MTL were matched to 254 MSTL patients using the nearest available score matching. The LNs resected during MSTL were paraesophageal and preparatracheal LNs in the upper mediastinum, in addition to those resected during standard two-field lymphadenectomy. RESULTS: RLN LNs were those most commonly affected by nodal metastasis in our series (26 %). Metastasis in RLN LNs was found in around 35, 25, and 20 % of patients with cancer in the upper, middle, and lower thoracic esophagus, respectively. LN metastasis was confined to the RLN region in 49 patients. Even 35 % of patients with pT1 tumors had positive RLN LNs. MTL increased the mean number of resected LNs when compared to MSTL (29 vs.15; p < 0.001). Recurrence was more frequent in those assigned MSTL than those assigned MTL (p < 0.001). The 5-year overall survival (OS) and disease-free survival (DFS) rate for MTL were 50.7 and 42 % compared to 35.3 and 28.2 % for MSTL (both p < 0.001), respectively. Postoperative complications were more frequent following MTL when compared to the MSTL. However, no statistically significant difference in postoperative complications was observed between the two groups. CONCLUSIONS: Adding the removal of RLN LNs might improve OS and DFS with acceptable morbidity for patients with ESCC. PMID- 24241967 TI - Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival. AB - Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC (p = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk. PMID- 24241969 TI - Existence of the sugar-bisulfite adducts and its inhibiting effect on degradation of monosaccharide in acid system. AB - Degradation of fermentable monosaccharides is one of the primary concerns for acid prehydrolysis of lignocellulosic biomass. Recently, in our research on degradation of pure monosaccharides in aqueous SO2 solution by gas chromatography (GC) analysis, we found that detected yield was not actual yield of each monosaccharide due to the existence of sugar-bisulfite adducts, and a new method was developed by ourselves which led to accurate detection of recovery yield of each monosaccharide in aqueous SO2 solution by GC analysis. By the use of this method, degradation of each monosaccharide in aqueous SO2 was investigated and results showed that sugar-bisulfite adducts have different inhibiting effect on degradation of each monosaccharide in aqueous SO2 because of their different stability. In addition, NMR testing also demonstrated possible existence of reaction between conjugated based HSO3(-) and aldehyde group of sugars in acid system. PMID- 24241970 TI - Investigations on hydrolytic activities from Stachybotrys microspora and their use as an alternative in yeast DNA extraction. AB - Stachybotrys microspora is a filamentous fungus characterized by the secretion of multiple hydrolytic activities (cellulolytic and non-cellulolytic enzymes). The production of these biocatalysts was studied under submerged culture using glucose, cellulose, and wheat bran as carbon sources. Endoglucanases, pectinases, xylanases, beta-glucanases, chitinases, and proteases were induced on cellulose based medium and repressed on glucose in both strains with higher amounts produced by the mutant. beta-glucosidases were roughly equally produced by both strains under glucose and cellulose conditions. The yield of chitinases, beta glucanases, and proteases produced by Stachybotrys strains was as much higher than the commercialized lysing enzyme called "zymolyase," currently used in yeast DNA extraction. In this context, we showed that S. microspora hydrolases can be successfully applied in the extraction of yeast DNA. PMID- 24241968 TI - Birth weight and risk factors for cardiovascular disease and type 2 diabetes in US children and adolescents: 10 year results from NHANES. AB - Previous studies have shown that birth weight and other birth characteristics may be associated with risk for type 2 diabetes and cardiovascular disease (CVD) later in life; however, results using large US national survey data are limited. Our goal was to determine the aforementioned associations using nationally representative data. We studied children and adolescents 6-15 years using data from the National Health and Nutrition Examination Survey cycles 2001-2010. Survey and examination data included demographic and early childhood characteristics, current health status, physical activity information, anthropometric measurements, dietary data (total energy, saturated fat, sodium, and sugar intakes), biomarkers related to selected risk factors of CVD [systolic blood pressure (SBP), plasma C-reactive protein (CRP) and lipid profiles], and type 2 diabetes [fasting glucose, insulin, and homeostasis model assessment (HOMA)]. Birth weight (proxy-reported) was inversely associated with SBP among girls; SBP levels increased 1.4 mmHg for each 1,000 g decrease in birth weight (p = 0.003) after controlling for potential confounders. Birth weight was not associated with levels of CRP or lipid profiles across the three racial groups. In addition, birth weight was inversely related to levels of fasting insulin and HOMA among non-Hispanic Whites; for each 1,000 g decrease in birth weight, fasting insulin levels increased 9.1% (p = 0.007) and HOMA scores increased 9.8% (p = 0.007). Birth weight was inversely associated with the levels of SBP, fasting insulin, and HOMA. These results support a role for birth weight, independent of the strong effects of current body weight status, in increasing risk for CVD and type 2 diabetes. PMID- 24241971 TI - Alcoholic fermentation with flocculant Saccharomyces cerevisiae in fed-batch process. AB - Studies have been conducted on selecting yeast strains for use in fermentation for ethanol production to improve the performance of industrial plants and decrease production costs. In this paper, we study alcoholic fermentation in a fed-batch process using a Saccharomyces cerevisiae yeast strain with flocculant characteristics. Central composite design (CCD) was used to determine the optimal combination of the variables involved, with the sucrose concentration of 170 g/L, a cellular concentration in the inoculum of 40% (v/v), and a filling time of 6 h, which resulted in a 92.20% yield relative to the theoretical maximum yield, a productivity of 6.01 g/L h and a residual sucrose concentration of 44.33 g/L. With some changes in the process such as recirculation of medium during the fermentation process and increase in cellular concentration in the inoculum after use of the CCD was possible to reduce the residual sucrose concentration to 2.8 g/L in 9 h of fermentation and increase yield and productivity for 92.75% and 9.26 g/L h, respectively. A model was developed to describe the inhibition of alcoholic fermentation kinetics by the substrate and the product. The maximum specific growth rate was 0.103 h(-1), with K(I) and K(s) values of 109.86 and 30.24 g/L, respectively. The experimental results from the fed-batch reactor show a good fit with the proposed model, resulting in a maximum growth rate of 0.080 h(-1). PMID- 24241972 TI - Gingival tissue healing following Er:YAG laser ablation compared to electrosurgery in rats. AB - The erbium-doped yttrium aluminum garnet (Er:YAG) laser is currently used for periodontal soft tissue management with favorable outcomes. However, the process of wound healing after Er:YAG laser (ErL) treatment has not been fully elucidated yet. The aim of this study was to investigate the gingival tissue healing after ErL ablation in comparison with that after electrosurgery (ElS). Gingival defects were created in 28 rats by ablation with ErL irradiation or ElS. The chronological changes in wound healing were evaluated using histological, histometrical, and immunohistochemical analyses. The ErL-ablated gingival tissue revealed much less thermal damage, compared to the ElS. In the ElS sites, the postoperative tissue destruction continued due to thermal damage, while in the ErL sites, tissue degradation was limited and the defects were re-epithelialized early. Heat shock protein (Hsp) 72/73 expression was detected abundantly remote from the wound in the ElS, whereas it was slightly observed in close proximity to the wound in the ErL sites. Hsp47 expression was observed in the entire connective tissue early in the wound healing and was found limited in the wound area later. This phenomenon proceeded faster in the ErL sites than in the ElS sites. Expression of proliferating cell nuclear antigen (PCNA) persisted in the epithelial tissue for a longer period in the ElS than that in the ErL. The ErL results in faster and more favorable gingival wound healing compared to the ElS, suggesting that the ErL is a safe and suitable tool for periodontal soft tissue management. PMID- 24241974 TI - (Z,Z)-5,27-Tritriacontadiene: Major sex pheromone ofDrosophila pallidosa (Diptera; Drosophilidae). AB - A crude cuticular extract from both sexes of 3660 fruit flies (Drosophila pallidosa) was subjected to SiO2 and AgNO3/SiO2 column chromatography, accompanied by bioassay for the sex pheromone activity. After three chromatographic steps, the active fraction was obtained. The main component of the active fraction was determined to be (Z,Z)-5,27-tritriacontadiene [(Z,Z)-5,27 C33:2, on the basis of gas-liquid chromatographic analysis, chemical derivatization and gas chromatography-mass spectrometry. Synthetic (Z,Z)-5,27 C33:2 at 5 female equivalents (FE) elicited a clear courtship response with a high courtship index amongD. pallidosa males. Therefore it was concluded that (Z,Z)-5,27-C33:2 was a major sex pheromone component in this species. PMID- 24241973 TI - The dawn of computer-assisted robotic osteotomy with ytterbium-doped fiber laser. AB - Currently, laser radiation is used routinely in medical applications. For infrared lasers, bone ablation and the healing process have been reported, but no laser systems are established and applied in clinical bone surgery. Furthermore, industrial laser applications utilize computer and robot assistance; medical laser radiations are still mostly conducted manually nowadays. The purpose of this study was to compare the histological appearance of bone ablation and healing response in rabbit radial bone osteotomy created by surgical saw and ytterbium-doped fiber laser controlled by a computer with use of nitrogen surface cooling spray. An Ytterbium (Yb)-doped fiber laser at a wavelength of 1,070 nm was guided by a computer-aided robotic system, with a spot size of 100 MUm at a distance of approximately 80 mm from the surface. The output power of the laser was 60 W at the scanning speed of 20 mm/s scan using continuous wave system with nitrogen spray level 0.5 MPa (energy density, 3.8 * 10(4) W/cm(2)). Rabbits radial bone osteotomy was performed by an Yb-doped fiber laser and a surgical saw. Additionally, histological analyses of the osteotomy site were performed on day 0 and day 21. Yb-doped fiber laser osteotomy revealed a remarkable cutting efficiency. There were little signs of tissue damage to the muscle. Lased specimens have shown no delayed healing compared with the saw osteotomies. Computer-assisted robotic osteotomy with Yb-doped fiber laser was able to perform. In rabbit model, laser-induced osteotomy defects, compared to those by surgical saw, exhibited no delayed healing response. PMID- 24241975 TI - Herbivore-induced volatile emissions from cotton (Gossypium hirsutum L.) seedlings. AB - The effect of herbivory on the composition of the volatile blends released by cotton seedlings was investigated by collecting volatiles from undamaged, freshly damaged (0-2 hr after initiation of feeding), and old damaged (16-19 hr after initiation of feeding) plants on which corn earworm caterpillars (Helicoverpa zea Boddie) were actively feeding. A blend of 22 compounds was consistently observed to be emitted by the old damaged plants with nine occurring either only in, or in significantly greater amounts in old damaged, as compared with freshly damaged plants. These were (Z)-3-hexenyl acetate, hexyl acetate, (E)-beta-ocimene, (3E) 4,8-dimethyl-1,3,7-nonatriene, (Z)-3-hexenyl butyrate, (E)-2-hexenyl butyrate, (Z)-3-hexenyl 2-methylbutyrate, (E)-2-hexenyl 2-methylbutyrate, and indole. The nature of this response is compared with other studies where herbivore-induced volatile responses are also known. The presence of large amounts of terpenes and aldehydes seen at the onset of feeding and the appearance of other compounds hours later suggest that cotton defense mechanisms may consist of a constitutive repertoire that is augmented by an induced mechanism mobilized in response to attack. A number of the induced compounds are common to many plants where, in addition to an immediate defensive function, they are known to be involved in the attraction of natural enemies. PMID- 24241976 TI - Fathead minnows use chemical cues to discriminate natural shoalmates from unfamiliar conspecifics. AB - Naturally occurring shoals of fathead minnows (Pimephales promelas) were captured and individuals given the choice between shoalmates and unfamiliar conspecifics in a two-choice discrimination test. When presented with chemosensory cues alone or with both chemosensory and visual cues, minnows exhibited a significant preference for shoalmates versus unfamiliar conspecifics. With visual cues alone, there was no significant discrimination of shoalmates. A second set of trials was conducted to ensure that minnows were choosing natural shoalmates and not just individuals with which they were held in the laboratory. When given the choice between unfamiliar conspecifics and shoalmates from which they were separated for a minimum of two months, minnows exhibited a significant preference for shoalmates. Taken together, these data suggest that fathead minnows are able to discriminate among conspecifics on the basis of familiarity using chemosensory cues, even after a relatively long separation. The ability to discriminate among conspecifics may facilitate: (1) the maintenance of kin groups or groups that share similar foraging or predator avoidance patterns or (2) the recognition of former shoalmates after some period of separation. PMID- 24241977 TI - Beaver (Castor canadensis) responses to major phenolic and neutral compounds in castoreum. AB - North American beaver (Castor canadensis) mark their territories with castoreum, a chemically complex secretion from their castor sacs. The phenolic and neutral fractions of castoreum have been shown to elicit specific behavioral responses from beavers in a field setting. Our objective was to identify compounds/mixtures that evoked responses similar to those stimulated by castoreum. We assayed recently identified phenolic compounds, some phenolics that had been determined to be biologically active in previous studies, the neutral compound borneol, and combinations of phenolic compounds, neutral compounds, and the two combined. Biological activity was measured by the elicitation and extent of specific responses and their strength (duration, frequency, and proportion of beavers responding). Generally, single compounds stimulated fewer responses than mixtures. A 26-compound mixture of phenolic and neutral compounds elicited responses in a similar proportion of trials as castoreum. However, responses to castoreum were stronger than to any synthetic sample. Further investigation of different measures of response, namely, elicitation, completeness, and strength, are deemed necessary to fully decipher the design of social odors. PMID- 24241978 TI - Chiral esters: Sex pheromone of the bagworm,Oiketicus kirbyi (Lepidoptera: Psychidae). AB - Gas chromatographic-electroantennographic detection (GC-EAD) analyses of pheromone extract of female bagworms,Oiketicus kirbyi (Guilding), revealed five EAD-active compounds. Retention index calculations, GC-mass spectrometry in both full-scan and selected-ion monitoring modes and GC-EAD analyses of authentic standards identified the compounds as 1-methylbutyl octanoate (MBO), 1 methylbutyl nonanoate (MBN), 1-methylbutyl decanoate (MBD), 1-methylpentyl decanoate (MPD), and 1-methylbutyl dodecanoate (MBDD). Of these five chiral esters, MBD was most abundant in extracts and elicited the strongest antennal response. In field experiments in Costa Rica, (R)-MBD attractedO. kirbyi males, whereas (S)-MBD in combination with (R)-MBD inhibited response.R but notS enantiomers of MBO, MBN, and MBDD strongly synergized attraction to (R)-MBD. (S) MBO and (S)-MBDD were inactive, whereas (S)-MBN was inhibitory. (R)-, (S)- and racemic MPD were inactive. Blends of (R)-MBD in ternary combination with either (R)-MBO and (R)-MBN or (R)-MBN and (R)-MBDD were as attractive as the five-ester blend. Five- and four-ester blends were equally attractive, suggesting redundancy of pheromone components for attraction of males. The multiple sex pheromone component blend of chiral esters inO. kirbyi may have evolved to maintain species specific communication in bagworm communities of tropical Americas. PMID- 24241979 TI - Feeding behavior of graminivorous grasshoppers in response to host-plant extracts, alkaloids, and tannins. AB - Secondary metabolites exhibit the potential to direct food selection by grass feeding (graminivorous) grasshoppers. We examined the effects of plant extracts and representative secondary metabolites on the feeding behavior of two such grasshoppers,Ageneotettix deorum (Scudder) andPhoetaliotes nebrascensis (Scudder). Three alkaloids and two tannins were bioassayed for their activity as feeding deterrent allelochemicals, as were extracts from the foliage of the graminoids commonly eaten by these grasshoppers:Agropyron smithii Rydb.,Andropogon hallii Hack.,Andropogon scoparius Michx.,Bouteloua gracilis (H. B. K) Lag. ex Griffiths,Carex heliophila Mack. andStipa comata Trin. & Rupr. Alkaloids strongly deterred feeding but tannins only exhibited a weak effect, even when present at four times the concentration of total phenolics typical for these graminoids. Host-plant extracts also exhibited weak effects, such that we found no evidence for either strong deterrence or phagostimulation. Our results for alkaloids and host-plant extracts are consistent with the view that grass feeding grasshoppers may be restricted to graminoids because of: (1) the presence of deterrents in nonhosts and (2) the absence of deterrents in hosts. However, our data for tannins show that these are unlikely to be effective barriers to herbivory by these grasshoppers. PMID- 24241980 TI - Inhibition of salvinia (Salvinia molesta Mitchell) by parthenium (Parthenium hysterophorus L.). I. Effect of leaf residue and allelochemicals. AB - Parthenium (Parthenium hysterophorus L.) leaf residue (LP, leaf powder) inhibited salvinia (Salvinia molesta Mitchell) biomass and the number of healthy fronds at 0.25% (w/v) and killed the treated plants at and above 0.75% (w/v) in about 5-15 days, depending on the quantity of the residue. At the lethal dose, the LP caused an abrupt desiccation of above-water plant parts, probably due mainly to root dysfunction. This was concurrent with the loss of dehydrogenase activity in, and an increase in solute leakage from, the roots and loss of chlorophylla, b, and total chlorophyll contents in the fronds, resulting in death of the treated plants. The LP appears inhibitory to salvinia through affecting macromolecules proteins, lipids, and nucleic acids. The inhibitory activity of LP at the lethal dose suspended in water was completely lost when allowed to stand for 30 days under outdoor conditions and promoted growth of the salvinia plants placed in it. The standard allelochemicals, including those present in parthenium LP, except parthenin andp-hydroxybenzoic acid, did not inhibit growth up to 100 ppm. However, parthenin andp-hydroxybenzoic acid killed salvinia plants at 100 and 50 ppm, respectively. Sincep-hydroxybenzoic acid is unlikely to be present at such a high concentration, parthenin appears to be one of the main allelochemicals responsible for the inhibitory effect of parthenium leaf residue on salvinia. PMID- 24241981 TI - Inhibition of salvinia (Salvinia molesta Mitchell) by parthenium (Parthenium hysterophorus L.). II. Relative effect of flower, leaf, stem, and Root residue on Salvinia and Paddy. AB - The relative effect of parthenium (Parthenium hysterophorus L.) plant residue on growth of salvinia and paddy seedlings was studied. The inhibitory activity of the residue as shown by its effect on the number of healthy fronds (HFN) and biomass was in the order: flower and leaf > stem and root. The flower (FP) and leaf (LP) residue was lethal at and above 0.75% (w/v, the convention used throughout), and inhibitory at lower doses. The stem (SP) and root (RP) residue supported growth of salvinia at lower doses and were slightly inhibitory at higher (1.25%) dose. All the above residue types supported the growth of paddy seedlings except at 1.25%, the highest concentration tested, which was slightly inhibitory. The amounts of chlorophylla, b, total chlorophyll, and carotenoid pigments in the leaves of the paddy seedlings grown in the medium were comparable to the amounts in the leaves of seedlings grown in distilled water. This demonstrates beneficial effects of the treatments. The study shows that salvinia is more sensitive to allelochemicals released by FP and LP into the aqueous medium. Both salvinia and paddy responded similarly to SP and RP by supporting growth at lower doses, probably due to lower levels of inhibitors. The results are discussed with reference to the possible role of allelopathy by parthenium on the population dynamics of aquatic weeds in natural ecosystems. PMID- 24241982 TI - Bisabolene epoxides in sex pheromone innezara viridula (L.) (Heteroptera: Pentatomidae): Role ofcis isomer and relation to specificity of pheromone. AB - Thetrans- andcis-(Z)-alpha-bisabolene epoxides (trans- andcis-(Z)-alphaBE) are the main components of the male sex pheromone inNezara viridula. The role of thecis isomer and the importance of thecis/trans proportion for the activity and the specificity of the pheromone are not clearly elucidated and were studied here. Interindividual variation of thecis/trans proportion produced by males was studied by individual hexanic extracts in two strains originating from the south of France (SF) and French West Indies (FWI). Thetrans isomer composed 42-82% of bisabolene epoxides in SF males and 74-94% of bisabolene epoxides in FWI males. Means (+/- SD) significantly differ between SF (62.8%+/-8.4) and FWI (82.4%+/ 5.9) males in spite of this interindividual variation. Different isomers of bisabolene epoxide were synthesized and their EAG activity on female antennae was compared. Racemictrans- andcis-(Z)-alphaBE elicited low EAGs, not different from the nonnaturaltrans andcis (E)-alphaBE that were inactive on behavior. Behavioral tests revealed that racemictrans- andcis-(Z)-alphaBE attracted 45% (P<0.05) and 25% (P<0.05) of females, respectively. The same levels of attraction were obtained with (-) enantiomers oftrans- andcis-(Z)-alphaBE, which attracted 40% (P<0.05) and 20% (P>0.05) of the females, respectively. Binary blends containing 75/25, 50/50, and 25/75 proportions ofcis/trans isomers were more attractive thantrans-(Z)-alphaBE alone and response of females to the 25%cis/75%trans blend was significantly more important than the response totrans-isomer alone (P<0.05). The importance of thecis/trans proportion in relation with the specificity of the male pheromone is discussed. PMID- 24241983 TI - Interspecies differences and variability with time of protein precipitation activity of extractable tannins, crude protein, ash, and dry matter content of leaves from 13 species of Nepalese fodder trees. AB - Dry matter, ash, crude protein, and protein precipitation activity (PPA) of 13 Nepalese tree fodder species were monitored in dried samples prepared monthly between November 1990 and May 1991, and additionally in November 1991, covering the season when they are particularly important as fodder. Monthly levels of dry matter, ash, and crude protein were fairly stable except when there was new leaf growth, although year to year differences in dry matter were found inBrassaiopsis hainla (Bh),Dendrocalamus strictus (Ds),Ficus roxburghii (Fr), andQuercus semecarpifolia (Qs). Tannin PPA fluctuated considerably inArtocarpus lakoocha (Al),Ficus glaberrima (Fg),F. nerrifolia (Fn), Fr,F. semicordata (Fs),Litsea polyantha (Lp), andPrunus cerasoides (Pc), and to a lesser extent in Bh,Castanopsis indica (Ci),C. tribuloides (Ct),Quercus lamellosa (Ql), and Qs. Similar fluctuations in PPA were observed in fresh leaf samples taken weekly. Ds did not have any detectable PPA. Trends in PPA fluctuation were generally similar for trees located at similar altitudes. Fr, Pc, Al, Fn, Ql, and Ci had falling PPAs before shedding leaves. Some of the fluctuations in Fr, Fs, Fg, Pc, and Lp were apparently due to changes in the extractability and quantity of condensed tannins. These fluctuations in PPA may affect the nutritive value of the fodders. PMID- 24241984 TI - Seasonal variation in phytotoxicity of bracken (Pteridium aquilinum L. Kuhn). AB - Laboratory bioassays were used to test for the phytotoxicity of volatile compounds, fresh plant material as a seed bed, and water extracts from bracken [Pteridium aquilinum (L.) Kuhn] pinnules to germination and seedling growth of aspen (Populus tremula L.) and Scots pine (Pinus sylvestris L.). Fronds were sampled from two bracken populations, one in the south and one in the north of Sweden. All three bioassays showed inhibitory effects, and these varied seasonally with the most inhibitory effects occurring in May, June, and September. The peak of inhibition in May and June coincides with the start of the growing season when bracken still is immature and vulnerable to interference from other species. The increase in inhibitory effects in September appears to be due to transformation of natural products or an accumulation of inhibitory compounds that are released during decomposition following frond death. Addition of activated carbon did not remove the inhibitory effects. PMID- 24241985 TI - Phloem sap collection from lettuce (Lactuca sativa L.): Methodology and yield. AB - Three methods to collect phloem sap on different lettuce lines were optimized and are described in detail. The success ratio for stylectomy of aphids was over 80% through the combination of a specially designed setup and electrical penetration graphs to monitor phloem sap ingestion. For unknown reasons on some lettuce lines stylets never showed sustained exudation. There were clear differences in stylet exudation between two aphid species on the same lettuce line. Honeydew collection in hexadecane made accurate quantitative analysis possible; samples were large and clean, but biotransformed. The EDTA chelation method produced large samples, but dilution, oxidation, and impurities from the wound surface reduced the reliability. PMID- 24241986 TI - Phloem sap collection from lettuce (Lactuca sativa L.): Chemical comparison among collection methods. AB - The chemical composition of phloem sap from lettuce, collected by three different methods, was compared. Phloem sap from stylectomy samples contained sucrose and 14 amino acids. Honeydew and EDTA chelation samples showed considerable breakdown of sucrose into fructose and glucose, several additional amino acids, and large differences in relative concentrations of amino acids, when compared to stylectomy samples. Honeydew contained considerable amounts of other oligosaccharides, and few proteins in low amounts, while EDTA showed many proteins. HPLC chromatograms showed numerous unidentified secondary plant compounds in honeydew and EDTA samples. Comparison of phloem sap samples from near-isogenic susceptible and resistant lines showed no relation of phloem sap composition with monogenic resistance to the aphidNasonovia ribisnigri. PMID- 24241987 TI - Aggregation pheromone of Australian SAP beetle,Carpophilus davidsoni (Coleoptera: Nitidulidae). AB - A male-produced aggregation pheromone was identified for the Australian sap beetle,Carpophilus davidsoni Dobson (Coleoptera: Nitidulidae), by bioassay-guided fractionation of volatiles collected from feeding beetles. The most abundant components were: (2E,4E,6E)-5-ethyl-3-methyl-2,4,6-nonatriene, (3E,5E,7E)-6-ethyl 4-methyl-3,5,7-decatriene, (2E,4E,6E,8E)-3,5,7-trimethyl-2,4,6,8-undecatetraene, and (2E,4E,6E,8E)-7-ethyl-3,5-dimethyl-2,4,6,8-undecatetraene. The relative abundance of these components in collections from individual males feeding on artificial diet was 100:7:9:31, respectively. Pheromone production began within several days after males were placed onto diet medium and continued for at least 20 weeks. Peak production was >3 ug total pheromone per male per day. Males in groups of 50-60 emitted less pheromone (the peak level was 0.09 ug per beetle per day), and the emissions from groups contained relatively little tetraene (proportions of the components listed above were 100:7:2:7, respectively). Three additional trienes and one additional tetraene were identified in minor amounts; the entire eight-component male-specific blend is qualitatively identical and quantitatively similar to that of the North American sibling species,C. freemani Dobson. A synthetic blend of the four major components on rubber septa, prepared to emit in the same proportions as from individual males, was highly attractive in the field when synergized with fermenting whole-wheat bread dough. Cross attraction was observed in the field involving the pheromones ofC. davidsoni, C. hemipterus (L.), andC. mutilatus Erichson. Potential uses of the pheromones in pest management are discussed. PMID- 24241988 TI - Discrimination of oilseed rape volatiles by honey bee: Novel combined gas chromatographic-electrophysiological behavioral assay. AB - A novel technique for the simultaneous monitoring of electroan-tennogram (EAG) and conditioned proboscis extension (CPE) responses of honey bees to the effluent from a gas chromatograph (GC) was developed to locate biologically active components in blends of plant volatiles and to investigate odor recognition at the peripheral and behavioral levels. A six-component mixture, comprising compounds previously identified as oilseed rape floral volatiles, was used as the stimulus. Standard CPE and EAG recordings were done as a reference. EAG responses were elicited from unconditioned bees by all the components presented either in the coupled or the standard mode. Conditioned bees gave larger EAG responses than unconditioned bees, suggesting that antennal sensitivity is enhanced by conditioning. At the behavioral level, in both the standard and the coupled modes, only conditioned bees showed the proboscis extension response, with the majority of individuals responding to linalool, 2-phenylethanol, and benzyl alcohol. PMID- 24241989 TI - Sequestration ofVeratrum alkaloids by specialistRhadinoceraea nodicornis konow (Hymenoptera, Tenthredinidae) and its ecoethological implications. AB - The larvae of the specialist sawflyRhadinoceraea nodicornis Konow (Hymenoptera, Tenthredinidae) store in their hemolymph ceveratrum alkaloids originating from the host plantVeratrum album L. (Liliales, Melanthiaceae). The major alkaloid found in the hemolymph is 3-acetyl-zygadenine. Qualitative and quantitative data showed that the plant alkaloid 3-angeloylzygadenine is most probably metabolized in the larval gut to zygadenine and then acetylated. A still unidentified alkaloid with a molecular weight of 591 Da was detected in plant leaves as well as in the gut, hemolymph, and excrement of larvae. Protoveratrine A and B, on the other hand, seem to be degraded by the larvae. These findings indicate that the pathway of ceveratrum alkaloids inR. nodicornis larvae is fourfold: direct sequestration, metabolism followed by sequestration, excretion of intact alkaloids, and degradation. In contrast, no ceveratrum alkaloids were detected in the hemolymph and excrement of larvae of the generalist sawflyAglaostigma sp. fed withV. album leaves. Bioassays with the antMyrmica rubra L. proved that the hemolymph ofR. nodicornis larvae is highly deterrent and toxic. In bioassays evaluating defensive efficiency against predators (ants, spiders, and bushcrickets), no larvae were eaten. Ceveratrum alkaloids were also detected in the hibernating prepupae ofR. nodicornis. In feeding bioassays, the shrewCrocidura russula Hermann rarely fed upon prepupae, suggesting that this stage is also protected from predation to some degree. In field surveys, the only parasitoids recorded were two ichneumonid species that are believed to be specialized onR. nodicornis. Bioassays and field observations enable us to suppose thatR. nodicornis and its enemies produce a food web of ion connectance. PMID- 24241990 TI - Olfactory reception of potential pheromones and plant odors by tarnished plant bug,Lygus lineolaris (Hemiptera: Miridae). AB - Olfactory reception of potential pheromones and host-plant odors by male and female tarnished plant bugs (TPBs),Lygus lineolaris (Hemiptera: Miridae), was investigated by utilizing electroantennogram (EAG) techniques. In general, EAGs were similar between the sexes. Among 31 compounds of seven chemical groups tested, insect-produced butyrates and host-plant-containing green leaf volatiles (GLVs) were the most active. Hexyl butyrate and (E)-2-hexenyl butyrate elicited greater EAGs in males than in females. Females responded with significantly greater EAGs to alcohol and aldehyde GLVs than to their acetate derivatives. Among GLVs, sexual dimorphism was also observed in response to (E)-2-hexenol and (E)-2-hexenal. Females were more sensitive to the monoterpene geraniol than were males. While nonanal was the most stimulatory compound tested, no sexual differences in EAGs to this compound were observed. These studies reveal olfactory receptors on TPB antennae responsive to insect and host-plant volatiles that are likely to play a role in host finding and sexual attraction. PMID- 24241991 TI - Sex pheromone of cranberry fruitworm,Acrobasis vaccinii riley (Lepidoptera: Pyralidae). AB - The following compounds and (approximate ratios) were identified in sex pheromone gland extracts of femaleAcrobasis vaccinii Riley by comparison of gas chromatography-mass spectrometric traces with those of synthetic standards: (E,Z) , (Z,E)-, (Z,Z), and (E,E)-8, 10-pentadecadien-l-ol acetates (100:1:2:12), a dodecen-l-ol acetate (8), (Z)-8-, (Z)-9-, and (E)-9-pentadecen-l-ol acetates (3:23:4), two heptadecen-l-ol acetates (4:4), tetradecyl, pentadecyl, hexadecyl, and heptadecyl acetates (3:15:10:8), dodecan-l-ol (6), tetradecan-l-ol (5), and hexadecan-l-ol (23). The amount of (E,Z)-8, 10-pentadecadien-l-ol acetate (E8,Z10 15:Ac) in the extract was about 0.5 ng/female. Electroantennographic analysis of gas chromatographic fractions of female sex pheromone gland extract showed that the fraction containingE8,Z10-15:Ac elicited the greatest response. Alone,E8,Z10 15:Ac failed to elicit upwind flight of males in flight-tunnel tests, and traps baited with it did not catch males in field experiments. WhenE8,Z10-15:Ac was combined with (E)-9-pentadecen-l-ol acetate (100:4), male upwind flight response in flight-tunnel tests was equivalent to those obtained with extract of female sex pheromone glands (synthetic, 62%; natural, 51%), but the percent of males flying upwind that contacted the source was lower (synthetic, 47%; natural, 88%). The lower percent of source contact elicited by the synthetic pheromone could be a result of the difference in isomer ratios of 8,10-15:Ac in the natural and synthetic pheromone or could indicate that the synthetic pheromone is incomplete. Traps baited with the 100:4 combination caught large numbers of males in field experiments. PMID- 24241992 TI - Identification, synthesis, and bioactivity of a male-produced aggregation pheromone in assassin bug,Pristhesancus Plagipennis (Hemiptera: Reduviidae). AB - Pristhesancus plagipennis, a large Australian assassin bug, possesses three pairs of dorsal abdominal glands (DAGs). In the male, the anterior and posterior glands are hypertrophied and secrete an attractant pheromone. Gas chromatography-mass spectrometry (GC-MS) analyses of male DAG extracts and airborne volatiles emitted from calling males showed the pheromone signature to be dominated by a novel component. Subsequent chemical manipulations, GC-MS, and chiral-column analyses established its identity as (Z)-3-hexenyl (R)-2-hydroxy-3-methylbutyrate. Minor components included 3-methylbutanol, 2-phenylethanol, (Z)-3-hexenol, decanal, (E) 2-hexenoic acid, and three minor hexenyl esters. Bioactivity studies using laboratory olfactometers and outdoor flight cages demonstrated attraction by femaleP. plagipennis to calling males, heptane extracts of male posterior DAGs and a synthetic formulation of the (Z)R enantiomer of the major ester, alone or in combination with other components of male anterior and posterior DAGs. Males were also attracted to the major ester. The racemate andS enantiomer of the ester were not attractive. Contamination of the (Z)R enantiomer with 30-60% of theE isomer also made the compound nonattractive. This is the first report of an aggregation pheromone in the Reduviidae. The prospects for pheromonal manipulation ofP. plagipennis populations to enhance the value of this predator in horticultural ecosystems, are discussed. PMID- 24241993 TI - Volatile secretions of old world army antAenictus rotundatus and chemotaxonomic implications of army ant dufour gland chemistry. AB - The Dufour glands ofAenictus rotundatus contain a complex mixture of terpenoids with geranylgeraniol comprising over 50% of the secretion. Some novel compounds have been tentatively identified as higher homologs of 1,3,3-trimethyl-2,7 dioxabicyclo[2,2,1]heptane based on GC-MS data. The Dufour gland secretion ofA. rotundatus is more similar in composition to the secretions of members of the subfamily Ecitoninae than to its closer relatives from the tribe Dorylini, a result that further complicates studies on the phylogeny of army ants. The mandibular glands ofA. rotundatus contain a mixture of 4-methyl-3-heptanone and limonene in trace amounts, and the well-developed postpygidial glands contain methyl anthranilate only. PMID- 24241994 TI - Ethanol and ambrosia beetles in Douglas fir logs with and without branches. AB - November-felled Douglas fir (Pseudotsuga menziesii (Mirb.) Franco) logs with and without branches were left lying on the forest floor through August. In May, as the logs were being colonized by ambrosia beetles,Trypodendron lineatum (Oliv.) andGnathotrichus retusus (LeConte), the ethanol, acetaldehyde, and water concentrations in the delimbed logs were significantly higher than in the branched logs. Since both log types received the same rainfall, lower water contents in branched logs was probably the result of absorbed water being transported through the branches via capillary movement and evaporation. Lower tissue water levels could have prevented the establishment and maintenance of anaerobic conditions, thus limiting the synthesis of acetaldehyde and ethanol in the branched logs. By late August, the beetle densities in delimbed logs were 9 16 times greater than in the branched logs. Log ethanol concentrations could be a key chemical factor affecting the ambrosia beetle attack densities. Acetaldehyde concentrations in the logs also may have affected the attack densities. PMID- 24241995 TI - Behavioral responses ofLittoraria irrorata (SAY) to water-borne odors. AB - Behavioral responses of the gastropod molluscLittoraria (=Littorina)irrorata indicate that it can discriminate among environmental odors. Snails were assayed for responses to 11 odors from plants and animals potentially representing food, shelter, location in the environment, and predators. Crushed conspecifics were included as an alarm odor. Except for odor of crushed conspecifics, all odor sources were water-borne from living intact organisms. Behavioral responses were categorized as no response, positive response, or negative response. For some analyses, negative responses were subdivided into withdrawing and turning responses. Snails responded positively to several plant odors. They did not respond to odors of intact conspecifics, fiddler crabs, or grass shrimp. They responded negatively to odors of a plant found at the upper limit of their minimal habitat, predatory blue crabs, crushed conspecifics, predatory gastropods, and ribbed mussels. Odors of blue crabs on different diets affect the type of negative response the snails display. PMID- 24241996 TI - Long-chain free fatty acids: Semiochemicals for host location by western corn rootworm larvae. AB - A bioassay-driven sequential fractionation scheme was used to isolate fractions of a crude dichloromethane maize seedling extract behaviorally active to larvae of the western corn rootworm,Diabrotica virgifera virgifera LeConte. (Z,Z)-9,12 Octadecadienoic (linoleic) acid, (Z)-9-octadecenoic (oleic) acid, and octadecanoic (stearic) acid were identified from a purified fraction of maize extract that was attractive to western corn rootworm larvae in choice tests with equal levels of carbon dioxide on both sides of the choice. When synthetic linoleic, oleic, and stearic acids were tested together in the amounts and proportions found in the attractive fraction (1000, 800, and 300 ng of linoleic, oleic, and stearic acids, respectively), significantly more western corn rootworm larvae were found on the side with synthetic free fatty acids plus carbon dioxide than on the side with carbon dioxide alone. Results of the choice-test bioassays were not significantly different when the synthetic blend of free fatty acids was substituted for the purified maize fraction. Neither the purified extract nor the synthetic blend was behaviorally active in preliminary single-choice experiments without carbon dioxide. Linoleic, oleic, and stearic acids were also tested individually in the choice test bioassay with carbon dioxide on both sides of the choice to determine a dose-response curve. Linoleic and oleic acid each had one dose that was significantly attractive in conjunction with carbon dioxide on both sides of the choice, but stearic acid was not active in the doses tested. PMID- 24241997 TI - Allelopathic potential of menthofuran monoterpenes fromCalamintha ashei. AB - A reversed-phase HPLC analysis was used to separate and quantify five menthofuran monoterpenes inCalamintha ashei leaf soaks and washes. (+)-Evodone and desacetylcalaminthone were the major constituents of both soaks and washes. Concentrations of (+)-evodone and desacetylcalaminthone were as high as 0.66 and 0.74 mM, respectively, in leaf soaks. The highest concentration of monoterpenes in leaf washes obtained by misting was 0.021 mM. Aqueous solubilities of the menthofurans were determined to exceed concentrations required for growth inhibition. Bioassays of individualCalamintha monoterpenes demonstrated effects on germination as low as 0.05 mM for (+)-evodone. An equimolar mixture of desacetylcalaminthone and (+)-evodone reducedRudbeckia hirta germination by 17% at a combined concentration of 0.025 mM forLeptochloa dubia. Confirmation of allelopathic effects byCalamintha ashei will require long-term bioassays ofCalamintha menthofurans on the growth of native sandhill species under conditions comparable to the harsh environment of the Florida scrub. PMID- 24241998 TI - Chemical defense of common antarctic shallow-water nudibranchTritoniella belli eliot (Mollusca: Tritonidae) and its prey,Clavularia frankliniana rouel (Cnidaria: Octocorallia). AB - Extracts of the dorid nudibranchTritoniella belli and stoloniferan coralClavularia frankliniana were chromatographed and analyzed by(1)H NMR and thin-layer chromatography. Three glycerol ethers were detected inT. belli, primarily 1-O-hexadecyl glycerol (chimyl alcohol). Chimyl alcohol was also detected after gradient flash chromatography and reverse-phase HPLC purification in the tissues ofC. frankliniana. The common omnivorous predatory Antarctic sea starOdontaster validus, a likely predator of benthic invertebrates, showed feeding deterrence to small cubes ofT. belli mantle tissue placed on the tube feet along the ambulacral feeding groove, while always extruding the cardiac stomach when presented with cubes of shrimp tissue of similar size. Filter-paper disks soaked in an aqueous shrimp solution and then dried were found to elicit a broad range of feeding behaviors inO. validus, including movement of the shrimp disk to the mouth, extrusion of the cardiac stomach, and the assumption of a humped feeding posture. Chimyl alcohol-treated shrimp disks caused significant feeding deterrence in sea stars when compared with control disks (solvent plus shrimp treated disks alone).T. belli andC. frankliniana appear to employ a defensive compound that has been found in a variety of temperate and tropical mollusks, where it has been demonstrated to deter fish predators. We provide evidence for further deterrent capabilities of chimyl alcohol and of its trophic relationship in the polar ecosystem of McMurdo Sound, Antarctica. PMID- 24241999 TI - Biological activity of (3R,5S,6R)- and (3S,5R,6S)-3,5-dimethyl-6-(methylethyl) 3,4,5,6-tetrahydropyran-2-one, a pheromone ofMacrocentrus grandii (Goidanich) (Hymenoptera: Braconidae). AB - In a previous study we reported identification of (3R*,5S*,6R*)-3,5-dimethyl-6 (methylethyl)-3,4,5,6-tetrahydropyran-2-one as a component of the pheromone ofMacrocentrus grandii Goidanich. The lactone was present in male and female wasps, and laboratory and field bioassays demonstrated that both sources of the lactone elicit flight initiation, upwind anemotaxis, and casting in male wasps. In the present study, the synthetic (3R,5S,6R)- and (3S,5R,6S)-lactone enantiomers (RSR andSRS, respectively) were bioassayed for biological activity. In wind tunnel studies theSRS enantiomer elicited flight initiation, upwind anemotaxis, and casting by male wasps comparable to lactone derived from male and female wasps. Flight response to theRSR enantiomer averaged 14 percent of theSRS enantiomer. No specific ratio of the stereoisomers was found more attractive than theSRS enantiomer alone. Field studies demonstrated theSRS enantiomer was active alone in attracting male wasps. When paired with (Z)-4-tridecenal (a previously identified female-derived sex pheromone), theSRS enantiomer yielded a synergistic response comparable to (Z)-4-tridecenal plus female-derived lactone. PMID- 24242000 TI - Strain-specific proteogenomics accelerates the discovery of natural products via their biosynthetic pathways. AB - The use of proteomics for direct detection of expressed pathways producing natural products has yielded many new compounds, even when used in a screening mode without a bacterial genome sequence available. Here we quantify the advantages of having draft DNA-sequence available for strain-specific proteomics using the latest in ultrahigh-resolution mass spectrometry for both proteins and the small molecules they generate. Using the draft sequence of Streptomyces lilacinus NRRL B-1968, we show a >tenfold increase in the number of peptide identifications vs. using publicly available databases. Detected in this strain were six expressed gene clusters with varying homology to those known. To date, we have identified three of these clusters as encoding for the production of griseobactin (known), rakicidin D (an orphan NRPS/PKS hybrid cluster), and a putative thr and DHB-containing siderophore produced by a new non-ribosomal peptide sythetase gene cluster. The remaining three clusters show lower homology to those known, and likely encode enzymes for production of novel compounds. Using an interpreted strain-specific DNA sequence enables deep proteomics for the detection of multiple pathways and their encoded natural products in a single cultured bacterium. PMID- 24242001 TI - Size-dependent propagation of Au nanoclusters through few-layer graphene. AB - We report the size-dependent propagation of gold nanoclusters through few-layer graphene (FLG). We employ aberration-corrected scanning transmission electron microscopy (STEM) to track the fate of Au55 and Au923 clusters that have been deposited, independently and isoenergetically, onto suspended FLG films using cluster beam deposition. We demonstrate that Au55 clusters penetrate through the FLG, whereas the monodisperse Au923 clusters reside at the surface. Our approach offers a route to the controlled incorporation of dopant nanoparticles and the generation of nanoscale defects in graphene. PMID- 24242002 TI - Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: what is the potential for prevention? AB - BACKGROUND: Assessment of the prevaccination type-specific prevalence of human papillomavirus (HPV) in the general population is important for the prediction of the impact of HPV vaccination. METHODS: We collected consecutively residual specimens from liquid-based cytology samples from 40,382 women from the general population in Copenhagen, Denmark, during 2002-2005. All samples were tested for high-risk HPV using the Hybrid Capture 2 technique, and genotyping was done using LiPa (Innogenetics). Through linkage with the Pathology Data Bank, we obtained information on the cytology result, and histology if any, on all women. RESULTS: The participants were 14-95 years of age (median age 37 years) at enrollment. The overall prevalence of HR HPV was 20.6 % ranging from 46.0 % in 20-23-year-old women to 5.7 % in women 65 years or older. Independently of cytology/histology, HPV16 was the most prevalent type. For virtually all HPV types, the occurrence of CIN3+ was higher when the specific HPV type was present together with HPV16 than it was together with other high-risk HPV types than HPV16 or if the HPV type occurred as a single infection. The prevalence of HPV16 and/or HPV18 was 74 % in cervical cancer and the corresponding prevalence of HPV16/18/31/33/45/52/58 was 89 %. CONCLUSION: This study forms a valuable starting point for monitoring the effect of HPV vaccination in Denmark. In addition, the particular carcinogenic role of HPV16 and 18 is confirmed and may support a role of genotyping for HPV16 and 18 in cervical cancer screening. PMID- 24242004 TI - The challenge of "Healthy People 2000". AB - The federal Office of Disease Prevention and Health Promotion (U.S. Public Health Service) has again prepared a compilation of goals and objectives for the health of the Nation's people, applicable to anticipated achievements within the decade ending in the year 2000. This effort involved work groups from numerous federal agencies, testimony in regional hearings from 800 citizens, and enrollment of a consortium of 300 national organizations. The final product, "Healthy People 2000," was released in September 1990, and contains 298 measurable objectives. Content regarding children, genetic disorders, developmental disabilities, and disabilities in general is less featured and less specific than was hoped for. Ten objectives of relatively direct concern to geneticists are discussed, plus 23 others of interest in the maternal and child health field. On balance, it is suggested that the Healthy People 2000 objectives can be useful and stimulating for workers in genetics, child health care, and disabilities' services. Regrettably, there was no simultaneous proposal of legislation that would provide new federal programs, funding, or assistance to states. PMID- 24242003 TI - Maspin influences response to doxorubicin by changing the tumor microenvironment organization. AB - Altered degradation and deposition of extracellular matrix are hallmarks of tumor progression and response to therapy. From a microarray supervised analysis on a dataset of chemotherapy-treated breast carcinoma patients, maspin, a member of the serpin protease inhibitor family, has been the foremost variable identified in non-responsive versus responsive tumors. Accordingly, in a series of 52 human breast carcinomas, we detected high maspin expression in tumors that progressed under doxorubicin (DXR)-based chemotherapy. Our analysis of the role of maspin in response to chemotherapy in human MCF7 and MDAMB231 breast and SKOV3 ovarian carcinoma cells transfected to overexpress maspin and injected into mice showed that maspin overexpression led to DXR resistance through the maspin-induced collagen-enriched microenvironment and that an anti-maspin neutralizing monoclonal antibody reversed the collagen-dependent DXR resistance. Impaired diffusion and decreased DXR activity were also found in tumors derived from Matrigel-embedded cells, where abundant collagen fibers characterize the tumor matrix. Conversely, liposome-based DXR reached maspin-overexpressing tumor cells despite the abundant extracellular matrix and was more efficient in reducing tumor growth. Our results identify maspin-induced accumulation of collagen fibers as a cause of disease progression under DXR chemotherapy for breast cancer. Use of a more hydrophilic DXR formulation or of a maspin inhibitor in combination with chemotherapy holds the promise of more consistent responses to maspin overexpressing tumors and dense-matrix tumors in general. PMID- 24242005 TI - Genetic counseling for deaf adults: Communication/language and cultural considerations. AB - It has been estimated that at least 50% of congenital or early onset deafness loss has a genetic etiology. Genetic services have traditionally been utilized by hearing parents of deaf children. Deaf adults could also greatly benefit from genetic counseling services. However, many deaf adults do not seek genetic services due in part to the communication/language and cultural differences of this group. Deaf people communicate in various ways including the use of sign language, oral communication, writing, or a combination of these modes. Also, while some deaf individuals are part of the hearing culture, others are part of the Deaf culture which has its own language, values, and traditions. Culturally Deaf individuals do not see themselves as handicapped or disabled. The genetic professional's awareness of the communication/language and cultural needs of this group, as well as their agency's responsibilities under section 504 of the Rehabilitation Act of 1973, may increase the accessibility of genetic services and contribute to the provision of successful genetic counseling for deaf adults. PMID- 24242006 TI - Breast cancer risk analysis: A genetic epidemiology service for families. AB - Breast Cancer Risk Analysis, a service for women with breast cancer and their families, makes use of information drawn from fields such as genetics, epidemiology, and counseling. Its aim is to provide individuals with background information and information regarding the etiology and risks of breast cancer. Based on this information, individuals are helped to make appropriate decisions pertaining to treatment and follow-up. While making use of some of the information and processes used in genetic counseling, Breast Cancer Risk Analysis differs from most types of genetic counseling for reproductive decisions. Some of these differences are discussed here. PMID- 24242007 TI - A project to strengthen linkages between genetic centers and child welfare services. AB - Genetic centers are reaching out to underserved populations. One of the most vulnerable underserved populations is children receiving child welfare services. Delivering genetic services to this group is particularly problematic because of multiple barriers. The first step in overcoming barriers is developing linkages between the genetic and adoption service systems with the goal of increasing referrals of child welfare clients to genetic services. This paper presents a model of fostering linkages that was developed under the auspices of the Mid Atlantic Regional Human Genetics Network with support from the Maternal and Child Health Bureau, Genetic Services Branch. Although the project was regional and funded, the model can be applied at the local level. PMID- 24242008 TI - Continuing education in genetics for Adoption workers in Wisconsin. AB - In response to 1982 legislation and 1984 changes in the Wisconsin Adoption Records Laws requiring the collection of a medical-genetic history at the time of termination of parental rights, a continuing education program in genetics was conducted for adoption workers in 1984 and 1985. The education program provided 14 workshops in five locations throughout the state and consisted of a variety of formats and levels of training. In all, 164 participants were trained at least at the introductory level with approximately 40 of these individuals taking part in the advanced levels of training. Evaluations of the training by participants and by a sample of the agency supervisors of trainees ranked the program very highly. A review of genetic history forms completed in post-training sessions verified the expectation that training was beneficial. Trained workers completing the medical-genetic history forms scored somewhat higher than untrained workers and much higher than parents who completed the forms without professional guidance. Medical-genetic history forms completed by birth fathers as part of step-parent adoptions contained little to no useful information about the birth father's genetic background. PMID- 24242009 TI - Genetics and adoption: Forming a partnership. AB - Genetic issues are demanding more attention in the area of public health. Adoption agencies and policymakers are beginning to address these issues where they relate to the adoption process and to the many families involved in adoption in this country. Genetic counselors need to play an active role as both educators of and consultants for adoption professionals and the families with whom they work. To facilitate a partnership between genetics and adoption we have developed a workshop intended to educate adoption professionals about the lifelong implications of genetic conditions on the adoption triad. PMID- 24242010 TI - Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-kappaB and p38 MAPK signaling pathways. AB - Since avian influenza virus H5N1-induced hypercytokemia plays a key role in acute lung injury, understanding its molecular mechanism is highly desirable for discovering therapeutic targets against H5N1 infection. In the present study, we investigated the role of autophagy in H5N1-induced lung inflammation by using H5N1 pseudotyped viral particles (H5N1pps). The results showed that H5N1pps significantly induced autophagy both in A549 human lung epithelial cells and in mouse lung tissues, which was primarily due to hemagglutinin (HA) of H5N1 virus. Blocking autophagy with 3-methyladenine (an autophagy inhibitor) or siRNA knockdown of autophagy-related genes (beclin1 and atg5) dramatically attenuated H5N1pp-induced proinflammatory cytokines and chemokines, such as IL-1beta, TNF alpha, IL-6, CCL2, and CCL5, both in vitro and in vivo. Autophagy-mediated inflammatory responses involved the activation of NF-kappaB and p38 MAPK signaling pathways, which required the presence of clathrin but did not rely on p62 or autophagosome-lysosome fusion. On the other hand, the activation of NF kappaB also promoted H5N1pp-induced autophagosome formation. These data indicated a positive feedback loop between autophagy and NF-kappaB signaling cascade, which could exacerbate H5N1pp-induced lung inflammation. Our data demonstrated an essential role of autophagy in H5N1pp-triggered inflammatory responses, and targeting the autophagic pathway could be a promising strategy to treat H5N1 virus-caused lung inflammation. PMID- 24242011 TI - Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators. AB - Inhaled nitric oxide (NO) and other cGMP- or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP- and cAMP dependent agonists. In precontracted near-resistance pulmonary arteries, the addition of sildenafil reduced vasorelaxation response to NO donor S-nitroso-N acetyl penicillamine (SNAP). A similar decrease in SNAP-induced vasodilation was observed in arteries pretreated with BAY 41-2272 (10(-9) M), a soluble guanylate cyclase stimulator cGMP, and its downstream protein kinase activator. cGMP also reduced the vasorelaxant response to the cAMP-dependent forskolin. Inhibition of endogenous vascular NO generation enhanced SNAP-induced relaxation. The present data suggest that the mechanism involved in the cGMP desensitization to other relaxant agonists involves downregulation of the small heat shock protein HSP20 and is evident in rat pulmonary and systemic vascular smooth muscle cells. In newborn rats with chronic hypoxia-induced pulmonary hypertension, the combination of sildenafil and inhaled NO resulted in a lesser reduction in pulmonary vascular resistance compared with their individual effect. These data suggest that clinical exposure to one cGMP-dependent pulmonary vasodilator may affect the response to other cGMP- or cAMP-mediated agonists. PMID- 24242013 TI - Confusion secondary to herpes simplex infection. PMID- 24242014 TI - A better way to know what patients believe and value about health. PMID- 24242012 TI - Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin injured lungs. AB - Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-alpha-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bleomycin-induced lung injury with systemic TSG-6 administration may produce therapeutic effects such as preventing the deterioration of lung function and increasing survival by modulation of the inflammatory cascade. Lung injury in C57Bl/6J mice was induced by intratracheal administration of bleomycin. Mice then received intravenous injections of TSG-6 or sham controls. Pulse oximetry was used to monitor changes in lung function. Cell infiltration was evaluated by flow cytometry, cytokine expression was measured by ELISA assays, and lungs were assessed for histological attributes. The results demonstrated that intravenous infusion of TSG-6 during the early inflammatory phase decreased cellular infiltration into alveolar spaces. Most importantly, it improved both the subsequent decrease in arterial oxygen saturation levels and the survival of the mice. These findings demonstrated that the beneficial effects of TSG-6 in a model of bleomycin-induced lung injury are largely explained by the protein modulating the early inflammatory phase. Similar phase-directed strategy with TSG-6 or other therapeutic factors that MSCs produce may be useful for other lung diseases and diseases of other organs. PMID- 24242016 TI - Overview of public policy and commercial gambling. PMID- 24242015 TI - T11TS inhibits glioma angiogenesis by modulation of MMPs, TIMPs, with related integrin alphav and TGF-beta1 expressions. AB - During glioma development, angiogenesis plays a crucial role in growth and vascularization of primary brain tumors. T11 target structure (T11TS), a bioactive molecule, has been documented as an anti-neoplastic agent in glioma induced rats and also in human glioma in vitro. This novel molecule induces apoptosis of tumor cells by way of immune potentiation and impairs the glioma cell cycle, but its role in glioma angiogenesis has not been worked out in detail. Matrix metalloproteinases (MMPs) are enzymes promoting tumor angiogenesis by enzymatically remodeling the extracellular matrix and altering surface protein expression such as integrin alphav and the matrix-bound proteins like TGF-beta1. The present study was formulated to assess the efficacy of T11TS in the modulations of MMP-2 and -9 and their endogenous inhibitors (TIMP-1 and TIMP-2) as well as modulations of integrin alphav and TGF-beta1 in glioma-induced rats and also on the phenotypic markers of endothelial cells (CD31 and CD34). The parameters used were zymography, western blot, and flow cytometric analyses. It was observed that T11TS administration significantly downregulates the expression of matrix metalloproteinase-2 and -9 along with its ligand integrin alphav and upregulates TIMP-1 and TIMP-2. In situ immunofluorescence and FACS results revealed that T11TS administration decreased the expression of the phenotypic markers (CD31/PECAM1, CD34), inhibiting the cell grip and also downregulating TGF beta1 expression (ELISA) from microglia cells in the glioma microenvironment. These results suggest that T11TS suppresses the expression of positive angiogenic growth factors and potentiates the expression of negative regulators in glioma associated endothelial cells (ECs), resulting in an anti-angiogenic effect on glioma-induced angiogenesis. PMID- 24242017 TI - Sucker bet or sure thing: A critical analysis of sports lotteries. AB - A paradox currently exists regarding legal sports gambling in North America: various forms are flourishing in Nevada, Oregon, and several Canadian provinces, while at the same time the United States Congress is conducting hearings on two bills that would prohibit any new state-sponsored sports gambling initiatives. This study examines the issue of why some jurisdictions are enthusiastic about legal sports gambling while others strongly resist the concept. In reviewing these divergent viewpoints, a case study of the newfledged Canadian "Sport Select" gambling format is presented. This example is used to highly the perils and payoffs of a typical state-sponsored sports gambling scheme, with a view toward broadening our understanding of how they work and how they might be fairer to the public. PMID- 24242018 TI - Gambling on sport: Policy issues. AB - The most significant public policy issue associated with sports betting is legalization. Supporters of legalization rest the bulk of their case on the economic benefits the state can experience. They also assert that legalization will have a major negative impact on the extent of illegal gambling. Those who are against further legalization, particularly amateur and professional sports leagues, the horse race industry, and legal bookmakers, point out that sports wagering is not very profitable and is very risky for the operator. Furthermore, legal wagering will be unable to compete effectively with the price of illegal operations. It is highly likely that the recently introduced federal legislation, S.474, Professional and Amateur Sports Protection Act, prohibiting further legalization of sports betting will be enacted. PMID- 24242019 TI - A little bit more evidence of lottery regressivity: The Kansas State Lottery. AB - This paper examines the existence of regressivity at the Kansas State Lottery using county level data. The classic "t-test" is used to test if the mean per capita bet in classes, defined as being below or above the median state income, are the same. The results show that the means of the per capita bets are not statistically different. Another test directly tests regressivity using the mean of bets expressed as a percentage of income. The results show that lower income counties bet more as a percentage of income. The second test also defines classes as being below or above the median educational level, labor force participation rate, employment rate, unemployment rate, population density, percentage white and the population size. The results show that Kansas runs a regressive lottery. PMID- 24242020 TI - The ethics of parimutuel systems. AB - One strand of the moral case for the superiority of parimutuel systems of betting over bookmaking emphasises that, as the name implies, the bettors are betting amongst themselves and that there is no discrimination against any individual bettor or groups of bettors. This claim is undermined by three deviations from the pure parimutuel principle found in many systems. Given that there is a close inverse relationship between the income/wealth of bettors and the average odds of the bets they place, the three deviations-higher deductions from long odds ("exotic") pools, higher deductions from pools when longer odds horses win and the paying of minimum dividends-each move a parimutuel system in the unethical direction ofregressive taxation. PMID- 24242021 TI - The future of Indian gaming. AB - The legal right for Native Americans to administer gambling on their land provides them with probably the most profitable opportunity currently available to generate tribal income. The federal Indian Gaming Regulatory Act which guarantees this right is frequently invoked in instances where Indian gaming is competitive with state or private commercial gambling interests. This article examines multiple aspects of the competitive conflicts which arise and provides some speculation about the future of Indian gaming. PMID- 24242022 TI - Accurately depicting pathological gamblers: Policy and treatment implications. AB - This paper describes results from a 3-year study of pathological gambling in the general population. Two distinct groups of pathological gamblers, based on income, were distinguished in the general population. These two groups varied considerably on several dimensions, including their demographic characteristics, gambling involvement and problematic gambling-related behaviors. These results contradict widely-accepted beliefs about the characteristics and behaviors of pathological gamblers and suggest that efforts in outreach, education and program development must be expanded to include types of pathological gamblers beyond those currently in treatment. PMID- 24242023 TI - Commercial gambling and values in American society: The social construction of risk. AB - Human existence is rooted in the individual's confrontation with risk from birth through death. Factors beyond individual control constantly produce random threats to the individual's welfare. The anxieties created by these events often cannot be resolved by the individual, but require the explanatory support of cultural values and belief systems. These values and belief systems allow a sense that socially managed activities can reduce adverse consequences to the individual in the face of random circumstances. This paper discusses the relationships among public policy, American values, and gambling as a cultural buffer to existential anxieties caused by chance events. PMID- 24242024 TI - Substitution of cyclophosphamide in the modified BuCy regimen with fludarabine is associated with increased incidence of severe pneumonia: a prospective, randomized study. AB - The modified busulfan-cyclophosphamide (mBuCy) regimen, combined with hydroxyurea, cytarabine and semustine, is the most frequently used myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation in our unit. It is unknown, however, whether fludarabine can be substituted for cyclophosphamide in the mBuCy regimen. We carried out a prospective study to compare modified busulfan-fludarabine (mBuF) with mBuCy, aiming to reduce the treatment-related mortality, with non-inferiority of other outcomes. The mBuCy regimen consisted of hydroxyurea 80 mg/kg on day -10; cytarabine 2 g/m(2) on day 9; busulfan 9.6 mg/kg, intravenously on day -8 through -6; and cyclophosphamide 3.6 g/m(2) on day -5 and -4 and semustine 250 mg/m(2) on day -3. In the mBuF regimen, cyclophosphamide was substituted with fludarabine 30 mg/m(2) through day -5 to -1. Mobilized blood and marrow stem cells were collected from HLA-matched siblings. The trial was suspended due to a tendency of higher incidence of severe pneumonia in the mBuF arm, in which 105 patients were enrolled. After follow-up for another 22 months, a significantly increased incidence of severe pneumonia (31.1 %) was observed in the mBuF arm (11.6 % in mBuCy). This finding suggests that it is uncertain whether it is appropriate to substitute fludarabine for cyclophosphamide under any drug combination. This study was registered at www.chictr.org/cn under identifier ChiCTR-TRC-09000470. PMID- 24242027 TI - [New approaches for the treatment of neurological diseases]. PMID- 24242026 TI - Association between local interleukin-6 levels and slow flow/microvascular dysfunction. AB - We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5 +/- 10.3 years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5%). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135-2.268; P = 0.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (OR = 8.065, CI 1.244-52.632; P = 0.029) and thrombus score (OR = 12.500, CI 1.100 142.857; P = 0.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274-2.281, P < 0.001; optimal threshold >=11.3 pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73% and specificity of 71%. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI. PMID- 24242025 TI - Bleeding complications related to warfarin treatment: a descriptive register study from the anticoagulation clinic at Helsingborg Hospital. AB - The most common indication for treatment with warfarin is the prevention of ischemic stroke in patients with atrial fibrillation. Time in therapeutic range (TTR) is an important tool to evaluate the quality of anticoagulation treatment. The aim of this study was to investigate the quality of treatment and the incidence of bleeding complications in patients on warfarin treatment treated by the anticoagulation clinic in Helsingborg. This is the first study that has specifically focused on the spontaneous reporting of bleeding complications in a real-world population. A total of 4,400 patients with a total of 8,394 patient years were registered, in the database Journalia AVK, during the time period November 1, 2007 to November 1, 2010. The mean age was 72 years. TTR was 73.3 % for the whole population. 421 patients suffered from haemorrhagic events. The frequency of major and fatal bleedings and intracranial haemorrhage (ICH) were 1.6, 0.2 and 0.5% per patient-year, respectively. A correlation between age and severe bleeding (major, fatal and ICH) (p = 0.003) was seen, but no correlation between gender and severe bleeding (p = 0.27). In 60 out of 455 bleeding events the complication had been reported to the anticoagulation clinic. At the anticoagulation clinic in Helsingborg the quality of warfarin treatment is good compared to previous results described in the literature, with regards to bleeding complications and efficacy. However, in our study, we confirm that the spontaneous reporting of bleeding complications related to warfarin is inadequate, and that review of patient records is needed to assure proper follow up. PMID- 24242028 TI - [Monoclonal antibodies and their targets in the treatment of multiple sclerosis]. PMID- 24242029 TI - [Neuroprotective approaches in neurology - dashed hopes?]. PMID- 24242030 TI - [Prevention of stroke]. PMID- 24242031 TI - [Progress in treatment of epilepsy]. PMID- 24242032 TI - Cellular mechanisms of ALS mutations - a loss or a gain of function? PMID- 24242033 TI - [Towards a vaccine against Alzheimer's?]. PMID- 24242034 TI - [Therapeutic concepts in Amyotrophic Lateral Sclerosis (ALS)]. PMID- 24242035 TI - [New developments in the neuro-oncology]. PMID- 24242036 TI - [New prospects for therapy in Parkinson's disease]. PMID- 24242037 TI - [Neuroinflammatory diseases with a focus on multiple sclerosis - an overview]. PMID- 24242038 TI - The brain barriers as therapeutic targets in neuroinflammation. PMID- 24242039 TI - [ How do we release T cells from an autoimmune disease of the central nervous system?]. PMID- 24242040 TI - Neuroprotective approaches in the animal model. PMID- 24242041 TI - The role of GM-CSF in multiple sclerosis. PMID- 24242042 TI - [Immunomodulation with oral dosage forms and their mechanisms of action]. PMID- 24242043 TI - Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation. AB - Rare genetic mutations in the DJ-1 and Parkin genes cause recessive Parkinsonism, however, the relationship between these two genes is not fully elucidated. Current emerging evidence suggests that these genes are involved in mitochondrial homeostasis, and that a deficiency in either of these two genes is associated with damages in mitochondrial function and morphology. In this study, we demonstrated that knockdown of DJ-1 expression or the overexpression of the DJ-1 L166P mutation results in a damaged phenotype in mitochondria and a hypersensitivity to H2O2-induced cell apoptosis. These phenotypes result from increased levels of endogenous oxidative stress. However, overexpression of wild type Parkin rescued the phenotypes observed in the mitochondria of DJ-1 knockdown and DJ-1 L166P mutant cells. We also determined that there were differences between the two cell models. Furthermore, both H2O2 treatment and the DJ-1 L166P mutation weakened the interaction between DJ-1 and Parkin. Taken together, these findings suggested that DJ-1 and Parkin were linked through oxidative stress, and that overexpression of Parkin protects DJ-1 protein-deficient and DJ-1 L166P mutant-expressing cells via inhibition of oxidative stress. PMID- 24242044 TI - miR-154 suppresses colorectal cancer cell growth and motility by targeting TLR2. AB - MicroRNAs play critical roles in the development and progression of colorectal cancer (CRC). miR-154 acts as a tumor suppressor in several tumors; however, its role in CRC is poorly understood. Herein, we found that miR-154 was decreased in CRC tissues and cell lines. Ectopic expression of miR-154 remarkably suppressed cell proliferation and colony formation, migration and invasion in CRC cells. The toll-like receptor 2 (TLR2) was found to be a direct target of miR-154 in CRC cells. Inhibition of TLR2 performed similar effects with miR-154 overexpression on CRC cells, and overexpression of TLR2 could significantly reverse the tumor suppressive effects of miR-154 on CRC cells. This study suggests an essential role for miR-154 in CRC. PMID- 24242045 TI - Participation of miR-200a in TGF-beta1-mediated hepatic stellate cell activation. AB - Hepatic stellate cell (HSC) activation is a pivotal event in the initiation and progression of hepatic fibrosis since it mediates transforming growth factor beta 1 (TGF-beta1)-driven extracellular matrix (ECM) deposition. MicroRNAs (miRNAs), small non-coding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key factors to regulate cell proliferation, differentiation, and apoptosis. Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in hepatic fibrosis is still poorly understood. The aim of this study is to investigate whether miR-200a could attenuate hepatic fibrosis partly through Wnt/beta-catenin and TGF-beta-dependant mechanisms. Our study found that the expression of endogenous miR-200a was decreased in vitro in TGF-beta1-induced HSC activation as well as in vivo in CCl4-induced rat liver fibrosis. Overexpression of miR-200a significantly inhibited alpha-SMA activity and further affected the proliferation of TGF-beta1-dependent activation of HSC. In addition, we identified beta-catenin and TGF-beta2 as two functional downstream targets for miR-200a. Interestingly, miR-200a specifically suppressed beta-catenin in the protein level, whereas miR-200a-mediated suppression of TGF beta2 was shown on both mRNA and protein levels. Our results revealed the critical regulatory role of miR-200a in HSC activation and implied miR-200a as a potential candidate for therapy by deregulation of Wnt/beta-catenin and TGFbeta signaling pathways, at least in part, via decreasing the expression of beta catenin and TGF-beta2. PMID- 24242047 TI - Fibroblast growth factor acts upon the transcription of phospholipase C genes in human umbilical vein endothelial cells. AB - Besides the control of calcium levels, the phosphoinositide-specific phospholipases C (PI-PLCs), the main players in the phosphoinositide signalling pathway, contribute to a number of cell activities. The expression of PI-PLCs is strictly tissue specific and evidence suggests that it varies under different conditions, such as tumour progression or cell activation. In previous studies, we obtained a complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for endothelial cells (EC), and demonstrated that the expression of the PLC genes varies under inflammatory stimulation. The fibroblast growth factor (FGF) activates the PI-PLC gamma1 isoform. In the present study, PI-PLC expression in FGF-treated HUVEC was performed using RT-PCR, observed 24 h after stimulation. The expression of selected genes after stimulation was perturbed, suggesting that FGF affects gene transcription in PI signalling as a possible mechanism of regulation of its activity upon the AkT-PLC pathway. The most efficient effects of FGF were recorded in the 3-6-h interval. To understand the complex events progressing in EC might provide useful insights for potential therapeutic strategies. The opportunity to manipulate the EC might offer a powerful tool of considerable practical and clinical importance. PMID- 24242049 TI - Volatile organic chemicals of a shore-dwelling cyanobacterial mat community. AB - The main components of a cyanobacterial mat community of a hypersaline lake shore consist of edaphic, mat-forming strains (ecophenes), and littoral strains ofOscillatoria animalis Agardh andO. subbrevis Schmidle, other microorganisms associated with these cyanobacteria, several species ofBembidion (Carabidae: Coleoptera), and two halophytic flowering plants:Puccinellia nuttalliana (salt meadow grass) andSalicornia europaea rubra (samphire). The volatile organic compounds of this community are a blend of those emitted by each of these components such as the C17 alka(e)nes, geosmin, 2-methylisoborneol,beta cyclocitral,beta-ionone, dimethyl sulfide, and dimethyl trisulfide of cyanobacteria and associated microorganisms; alcohols, esters, and aldehydes usually associated with flowering plants; and possibly some insect-derived esters, particularly isopropyl tetradecanoate. The dominant compounds were: C11, C13, C15, and C17 alka(e)nes, methyl esters of C16 and C18:2 acids, isopropyl tetradecanoate, heptanal, 3-octanone and 2-nonanone, the acyclic terpene linalool, and the alcohols 1-heptanol, 1-hexanol, 1-octanol, 3-hexen-1-ol, and 2 octen-1-ol. It is concluded that this community may be distinguished from related communities by its repertoire of volatile organic compounds. PMID- 24242048 TI - Lack of adenovirus DNA in mediastinal adipose tissue of obese/overweight adults with cardiovascular disorders? AB - Mediastinal adipose tissue can be found on the anterior surface of pericardial sac below the remnants of the thymus. On the basis of previous studies describing adenoviruses (AdVs) as a causative factor of obesity, the causative relation between the presence of AdVs and an increased accumulation of mediastinal adipose tissue was studied. The study included 25 obese/overweight subjects with cardiac disorders. Specimens from fat deposits from the anterior mediastinum were collected during cardiac surgery procedures. Afterwards, PCR was used to detect AdV-DNA. No AdV-DNA could be detected in adipose tissue. An association between an excessive accumulation of mediastinal adipose tissue and an AdV-infection in the development of accompanying cardiac disorders was excluded. PMID- 24242046 TI - Interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by JAK2- and PI3K-induced STAT1/3 in HepG2 hepatocyte cells. AB - Interleukin-6 (IL-6) is the major activator of the acute phase response (APR). One important regulator of IL-6-activated APR is peroxisome proliferator activated receptor alpha (PPARalpha). Currently, there is a growing interest in determining the role of PPARalpha in regulating APR; however, studies on the molecular mechanisms and signaling pathways implicated in mediating the effects of IL-6 on the expression of PPARalpha are limited. We previously revealed that IL-6 inhibits PPARalpha gene expression through CAAT/enhancer-binding protein transcription factors in hepatocytes. In this study, we determined that STAT1/3 was the direct downstream molecules that mediated the Janus kinase 2 (JAK2) and phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways in IL-6-induced repression of PPARalpha. Treatment of cells with pharmacological inhibitors of JAK2, PI3K, AKT, and mTOR attenuated the inhibitory effect of IL-6 on PPARalpha protein in a dose-dependent manner. These inhibitors also decreased the IL-6-induced repression of PPARalpha mRNA expression and promoter activity. Overexpression of STAT1 and STAT3 in HepG2 cells cotransfected with a reporter vector containing this PPARalpha promoter region revealed that both the expression plasmids inhibited the IL-6-induced repression of PPARalpha promoter activity. In the presence of inhibitors of JAK2 and mTOR (AG490 and rapamycin, respectively), IL-6-regulated protein expression and DNA binding of STAT1 and STAT3 were either completely or partially inhibited simultaneously, and the IL-6-induced repression of PPARalpha protein and mRNA was also inhibited. This study has unraveled novel pathways by which IL-6 inhibits PPARalpha gene transcription, involving the modulation of JAK2/STAT1-3 and PI3K/AKT/mTOR by inducing the binding of STAT1 and STAT3 to STAT-binding sites on the PPARalpha promoter. Together, these findings represent a new model of IL-6 induced suppression of PPARalpha expression by inducing STAT1 and STAT3 phosphorylation and subsequent down-regulation of PPARalpha mRNA expression. PMID- 24242050 TI - Evolution of behavioral responses to sex pheromone in mutant laboratory colonies ofTrichoplusia ni. AB - Male cabbage looper moths,Trichoplusia ni, from two colonies in which all females express an abnormal sex pheromone production phenotype were evaluated in a laboratory wind tunnel for upwind flight responses to the normal and abnormal sex pheromones. The abnormal sex pheromone blend consisted of 20 times as much (Z)-9 tetradecenyl acetate and 30-fold less (Z)-5-dodecenyl acetate compared to the normal pheromone blend. Initially, these males exhibited poor behavioral responses to the abnormal sex pheromone and maximum responses to the normal pheromone blend, indicating that there was no linkage between signal production and response. After 49 generations of laboratory rearing, males from the mutant colonies maintained good responses to the normal pheromone and increased their behavioral response to the abnormal sex pheromone to the same levels as for the normal pheromone. Over the same period, normal males maintained their preference for the normal pheromone. These results indicated that evolution had occurred in mutant colonies in favor of greater male responsiveness to the abnormal sex pheromone, resulting in the broadening of the response spectrum to pheromone blend ratios. This evolution presumably resulted from a mating advantage to those males that did not discriminate against mutant-type females in the mutant colonies. PMID- 24242051 TI - Analysis of secretions from scent-producing glands of brushtail possum (Trichosorus vulpecula Kerr). AB - A characterization at a molecular level of the chemical composition of the secretions of the two pairs of paracloacal glands and of the sternal sebum of the brushtail possum (Trichosorus vulpecula Kerr) has been undertaken with a view to evaluating the potential of volatile "pheromone" components as species-specific attractants for use in novel baiting systems. Particular attention has been given to the respective fatty acid fractions produced by chemical hydrolysis, since these are believed to be the products of postemission microbial degradation (fermentation) of the secretions. In all instances, the highly complex distribution of the constituents present in these organic components of the secretions were shown to be virtually identical in adult males and females. A unique suite of low-molecular-weight branched-chain carboxylic acids has been shown to be produced by chemical degradation of the holocrine (oil-secreting) gland secretion. This odor signature is suggested to function as a unique "scenting-the-habitat" pheromone that might act as an attractant to all members of the species. PMID- 24242052 TI - Spatial distribution of odors in simulated benthic boundary layer flows. AB - Many animals orient to odor sources in aquatic habitats where different flows and substrates affect the hydrodynamics of benthic boundary layers. Since the dispersal of chemicals is due to the fluid mechanics of a particular environment, we quantified the changes in the fine structure of an odor plume under different hydrodynamic conditions in the benthic boundary layer of a laboratory flume. We sampled turbulent odor plumes at 10 Hz using a microchemical sensor (150 um diameter) under two flow speeds: 3.8 and 14.4 cm/sec, and at 1, 8, 50 mm above the substrate. These distances above the substrate occur within different flow regions of the boundary layer and correlate with the location of crustacean chemosensory appendages within boundary layer flows. The high flow velocity exhibited a greater level of turbulence and had more discrete odor pulses than the low flow velocity. In general, odor signals showed a high level of temporal variation in fast flow at heights 1 and 8 mm above the substrate. In slow flow, temporal variation was maximal at 50 mm above the substrate, exhibiting more variance than the same height at the fast flow. These patterns of odor signals resulted in part from differences in the height above the substrate of the main axis of the odor plume at the two flow speeds. Our results imply that animals chemically orienting to an odor source will need to compensate for varying hydrodynamic properties of odor transport and dispersal. The method by which animals extract spatial information from odor plumes will need to account for changing flow conditions, or else it will not be equally efficient in extracting information about chemical spatial distributions. PMID- 24242053 TI - Field evaluation of synthetic compounds mediating oviposition inCulex mosquitoes (Diptera: Culicidae). AB - 3-Methylindole (skatole), a compound shown to be an oviposition attractant/stimulant forCulex quinquefasciatus in laboratory tests, was evaluated against natural populations of mosquitoes in the field. In experiments using paired black plastic tubs that contained water treated with an attractant solution containing a mixture of 3-methylindole, 4-methylphenol, 4-ethylphenol, phenol, and indole or that contained only tap water, the attractantbaited traps received significantly moreCx. quinquefasciatus egg rafts than did the untreated tap water. Gravid female traps that were baited with attractant solution collected significantly moreCx. quinquefasciatus females than did traps containing only tap water. There was no significant difference in number ofCx. quinquefasciatus collected in the traps baited with the attractant solution compared to the traps that contained water with 3-methylindole alone, indicating that 3-methylindole was solely responsible for the attraction. In replicated experiments conducted in experimental ponds, ponds that were treated with 3 methylindole received significantly moreCx. quinquefasciatus, Cx. tarsalis, andCx. stigmatosoma egg rafts than did untreated ponds. Experimental ponds treated with 3-methylindole at two levels (0.12 and 0.6 mg/liter) were equally attractive to ovipositingCx. quinquefasciatus. This is the first record of 3 methylindole showing attractancy/stimulation to ovipositingCx. stigmatosoma andCx. tarsalis under field or laboratory conditions. PMID- 24242054 TI - Identification of the antibiotic phomalactone from the entomopathogenic fungusHirsutella thompsonii var.synnematosa. AB - Dichloromethane extracts of culture broth from three strains of the entomopathogenic fungusHirsutella thompsonii var.synnematosa were toxic to two species of tephritid fruit fly and inhibited conidial germination in vitro in several other entomopathogenic fungi includingBeauveria bassiana, Tolypocladium spp., andMetarhizium anisopliae. A major metabolite, toxic to apple maggot,Rhagoletis pomonella, and inhibitory to conidial germination inB. bassiana, was isolated and identified as the antibiotic (+)-phomalactone, 6-(1 propenyl)-5,-6-dihydro-5-hydroxypyran-2-one. This is the first biologically active compound of low molecular weight isolated from the genusHirsutella. PMID- 24242055 TI - Tolerance of bitter compounds by an herbivore,Cavia porcellus. AB - Many plant defensive chemicals are bitter to humans. Because of this taste characteristic, and because bitter compounds are often toxic, such substances, and the plants that contain them, are regarded as generally unpalatable to wildlife. These assumptions may be unwarranted. To test the hypothesis that herbivores are indifferent to 'bitter' tastants, we investigated the responsiveness of guinea pigs (Cavia porcellus) to denatonium benzoate, denatonium saccharide, limonene,L-phenylalanine, naringin, quebracho, quinine, Ro Pel (a commercial animal repellent containing denatonium saccharide) and sucrose octaacetate. Only quinine and sucrose octaacetate slightly but significantly reduced feeding (P<0.05). Our findings are inconsistent with the notion that herbivores generally avoid what humans describe as bitter tastes. PMID- 24242056 TI - Allelopathy of oats. I. Assessment of allelopathic potential of extract of oat shoots and identification of an allelochemical. AB - The allelopathic potential of oat (Avena sativa L.) extracts was investigated under laboratory conditions. The ethyl ether-, acetone-, and water-soluble fractions obtained from the extract of oat shoots inhibited the germination and growth of roots and hypocotyls of lettuce (Lactuca sativa L.). The inhibitory activity of the water-soluble fraction was maximum, followed by that of ethyl ether-soluble and acetone-soluble fraction. An active principle of the water soluble fraction was isolated and its structure was determined by spectral data asL-tryptophan.L-Tryptophan inhibited the growth of hypocotyls and roots of lettuce seedlings at concentrations greater than 0.03 and 0.1 mM, respectively. These results suggested thatL-tryptophan may be an allelochemical which affects the growth or germination of different plant species. PMID- 24242057 TI - Allelopathy of oats. II. Allelochemical effect ofL-Tryptophan and its concentration in oat root exudates. AB - L-Tryptophan caused growth inhibition of roots and hypocotyls (or coleoptiles) of cockscomb (Amaranthus caudatus L.), lettuce (Lactuca sativa L.), cress (Lepidium sativum L.), timothy (Phleum pratense L.), rice (Oryza sativa L.), wheat (Triticum aestivum L.), and oat (Avena sativa L.), increasing the dose ofL tryptophan increased the inhibition. The concentrations for 50% inhibition of the root growth were 0.14, 0.15, 0.21, 0.79, 0.95, 1.7, and 2.4 mM for cockscomb, cress, lettuce, timothy, rice, wheat, and oat, respectively; the concentrations for 40% inhibition of the hypocotyl (or coleoptile) growth were 0.28, 0.33, 0.43, 2.7, 4.5, 7.2, and 15 mM for cockscomb, cress, lettuce, timothy, rice, wheat and oat, respectively. The levels ofL-tryptophan in oat seedlings and in its root exudates were 29.3 mg/kg fresh wt and 0.25 mM under light conditions, and 21.1 mg/kg fresh wt and 0.18 mM under dark conditions, respectively. The presence ofL tryptophan in the root exudates coupled with its effect on growth suggested thatL tryptophan may play an important role in the growth inhibition of other plants in nature. PMID- 24242058 TI - Tests and refinements of a general structure-activity model for avian repellents. AB - We tested the robustness of a structure-activity model for avian trigeminal chemoirritants. Fourteen benzoates and acetophenones were tested using European starlingsSturnus vulgaris as a bioassay. In general, the previously proposed model was a reasonable predictor of repellency (i.e., irritant potency). We found that the presence of a phenyl ring was critical to repellency. Basicity of the molecule is the next most critical feature influencing repellency. The presence of an acidic function within the electron-withdrawing functionality seriously detracts from repellency. The presence or absence of an electron-withdrawing or donating group may potentiate repellent effects, but its presence is not critical, so long as the phenyl ring is electron rich. Our data suggest that there is ano-aminoacetophenone/methyl anthranilate trigeminal chemoreceptor in birds analogous to the mammalian capsaicin receptor. Both receptors contain a benzene site. However, birds seem to lack the associated thiol/hydrogen-bonding site present in mammals which is needed to activate the benzene site. Rather, birds may possess an associated exposed charged site that in turn may interact with the stimulus to activate the benzene site. These differences may explain the differential sensitivity of birds and mammals to aromatic irritants. PMID- 24242059 TI - Use of water and EDTA extractions to estimate available (free and reversibly bound) phenolic acids in Cecil soils. AB - Sterile and microbe reinfested Cecil Ap and Bt soil materials amended with 0 to 5 umol/g of ferulic acid,p-coumaric acid,p-hydroxybenzoic acid, or vanillic acid were extracted after varying time intervals with water, EDTA, or NaOH to characterize sorption of cinnamic and benzoic acid derivatives and to determine the effectiveness of water and EDTA extractions in estimating concentrations of free and reversibly bound phenolic acids in soils. Basic EDTA (0.5 M, pH 8) extractions and water extractions provided good estimates of both free and reversibly bound cinnamic acid derivatives, but not of benzoic acid derivatives. Neutral EDTA (0.25 M, pH 7) and water extractions, however, were effective for both cinnamic and benzoic acid derivatives Rapid initial sorption of both cinnamic and benzoic acid derivatives was followed by slow long-term sorption of the cinnamic acid derivatives. Slow long-term sorption was not observed for the benzoic acid derivatives. The amount of sorption of phenolic acids in soil materials was directly related to the concentration of phenolic acids added to soil materials. The addition of a second phenolic acid to the soil materials did not substantially affect the sorption of each individual phenolic acid. Sodium hydroxide extractions, which were made only after phenolic acids in phenolic acid amended and non-amended soil material were depleted by microbes, confirmed that neutral EDTA and water extractions of soils can be used to make accurate estimates of baseline (residual) levels of free and reversibly bound phenolic acids available to soil microbes and, thus, potentially to seeds and roots. PMID- 24242060 TI - Mechanism of aggregation behavior inMaladera matrida Argaman (Coleoptera: Scarabaeidae). AB - AdultMaladera matrida Argaman (Coleoptera: Scarabaeidae: Melolonthinae) males emerge from soil for an active period at dusk, a few minutes before the females. Adults are found during most of the active hours on the foliage in aggregations composed of an equal sex ratio. The mechanism of aggregation behavior ofM. matrida beetles was studied in a Y-shaped olfactometer. No evidence was found for the existence of an aggregation pheromone released either by males or by females, but behavior tests indicate that adultM. matrida beetles, males as well as females, are attracted to volatiles of an injured host plant. The following scenario is suggested: Males emerge daily from soil at dusk, a few minutes before the females, and immediately start feeding. Additional males are attracted to the injured host's volatiles and form aggregations. When females emerge from soil, the attractant volatiles are concentrated in spots, and the females join the aggregations, forming an equal sex ratio. PMID- 24242061 TI - Leaf age affects composition of herbivore-induced synomones and attraction of predatory mites. AB - We investigated the olfactory response of the predatory mitePhytoseiulus persimilis to cucumber leaves infested with prey, the herbivorous spider miteTetranychus urticae. The predators responded to volatiles from young rather than old infested cucumber leaves. GC-MS analysis of the head-space of spider mite-infested, artificially damaged and undamaged cucumber plants showed that herbivore-induced plant volatiles were present among the volatiles of both old and young infested cucumber leaves. The major components of the herbivore-induced plant volatiles were (3E)-4,8-dimethyl-1,3,7-nonatriene and (E)-beta-ocimene: these compounds are known to attract the predatory mites. In addition, we found three oximes (2-methylbutanalO-methyloxime, 3-methylbutanalO-methyloxime, and an unknown oxime) in the headspace of both old and young infested cucumber leaves. 3 MethylbutanalO-methyloxime and the unknown oxime were much more abundant in the headspace of infested old cucumber leaves. The potential adaptive value of differential attractiveness of cucumber plant leaves of different age is discussed. PMID- 24242062 TI - Detoxification of cereal plant allelochemicals by aphids: Activity and molecular weights of glutathioneS-transferase in three species of cereal aphids. AB - The activity and molecular weights of glutathioneS-transferase were studied in three species of cereal aphid:Metopolophium dirhodum, Sitobion avenae, andRhopalosiphum padi. The highest level of glutathioneS-transferase activity was recorded in extracts fromM. dirhodum and the lowest fromS. avenae, and extracts of larvae were more active than those from adults. The activity of this enzyme was higher in extracts ofS. avenae andR. padi previously fed on a moderately resistant wheat variety than on a susceptible variety. Gel filtration followed by SDS-PAGE revealed three protein bands in the active fractions. The first had a molecular weight of 28,500 and the second of 27,500 and were present in all three species of aphid. The third protein differed in the three species, having a molecular weight of 26,000 inS. avenae, 25,500 inM. dirhodum, and 24,000 inR. padi. PMID- 24242063 TI - Role of Douglas fir (Pseudotsuga menziesii) carbohydrates in resistance to budworm (Choristoneura occidentalis). AB - The current year's growth of Douglas fir contains galactose, unusual in that this carbohydrate makes up 78.7% of the total carbohydrate fraction. An agar diet study was undertaken to determine the effects of galactose, other carbohydrates, and terpenes on western spruce budworm larval mortality, growth rate, and adult biomas production. All concentrations of the carbohydrates and terpenes tested, as well as other mineral elements not tested, were typical of the current year's foliage of Douglas fir. In experiment I, the diet containing 5.61% total carbohydrate did not significantly affect larval mortality when compared to the control diet. However, diets containing 9.45% and 15% total carbohydrate concentrations significantly increased larval mortality 64% and 96.1%, respectively, when compared to the control. Also in experiment I, terpenes alone (78.9% morality) and terpenes in combination with 9.45% and 15% total carbohydrates significantly increased larval mortality (97.2% and 100%, respectively) when compared to mortality on the control diet (44%). To determine which carbohydrate was causing the adverse effect, 6% glucose, 6% fructose, and 6% galactose were placed individually and in combination with terpenes in diets in experiment II. The 6% galactose diet significantly increased larval mortality and reduced growth rate when compared to the control, glucose, and fructose diets. Glucose resulted in 16% less larval mortality, significantly enhanced female larval growth rate and pupal weight, but did not affect male larval growth rate and pupal weight, when compared to the control. Fructose resulted in a significant decrease in larval mortality and a general trend of enhanced female and male larval growth rate and pupal weight. Larval mortality on terpenes alone was not significantly different from the control, but terpenes with 6% galactose increased larval mortality and decreased female and male growth rate and pupal weight significantly when compared to glucose-terpene and fructose-terpene diets. No significant interactions were found between carbohydrates and terpenes in either experiment. PMID- 24242064 TI - Interactions betweenKalmia and black spruce: Isolation and identification of allelopathic compounds. AB - Aqueous extracts of fresh leaves and organic soil of northern sheep laurel (Kalmia angustifolia var.angustifolia) were found to be inhibitory to the growth of black spruce (Picea mariana) germinants. Primary root growth of black spruce was more affected by the extracts than was shoot growth. The growth inhibition caused by the leaf extract was most pronounced under acidic conditions (pH 3-4). The aqueous extract ofKalmia leaves contained ferulic, vanillic, syringic, gentisic,m-coumaric,p-coumaric,o-hydroxyphenylacetic, andp-hydroxybenzoic acids as well as some other unknown compounds. These compounds were isolated from the aqueous extract ofKalmia leaves by ethyl acetate extraction and identified using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Bioassay indicated that the overall toxicity of the phenolic compounds to black spruce appeared to increase in the order ofo-hydroxyphenylacetic,p hydroxybenzoic, vanillic,p-coumaric, gentisic, syringic, ferulic, andm-coumaric acids. PMID- 24242065 TI - Oviposition stimulants inBarbarea vulgaris forPieris rapae andP. napi oleracea: isolation, identification and differential activity. AB - The closely related butterflies,Pieris rapae andP. napi oleracea, readily laid eggs onBarbarea vulgaris in greenhouse cages. When offered a choice between cabbage andB. vulgaris, P. rapae showed no preference, butP. napi oleracea preferredB. vulgaris. Bioassays of extracts ofB. vulgaris foliage revealed the presence of oviposition deterrent(s) in l-butanol extracts as well as stimulants in the postbutanol water extracts. However, the deterrent effect was apparently outweighed by the strong stimulatory effect in the whole plants. The postbutanol water extract was preferred over an equivalent cabbage extract by both species, but more significantly in the case ofP. napi oleracea. The stimulants were isolated by open column chromatography and HPLC, and the activity was associated with three glucosinolates.P. napi oleracea was more sensitive thanP. rapae to the natural concentration of compounds1 and3, whereas both species were strongly stimulated to oviposit by natural concentrations of compound2. Compounds1 and2 were identified as (2R)-glucobarbarin and (2S)-glucobarbarin, respectively, and3 was identified as glucobrassicin, on the basis of their UV, mass, and NMR spectra. When the pure compounds were tested at the same concentrations applied to bean plants, the (2R)-glucobarbarin at 0.2 mg/plant was preferred over a standard cabbage extract by both butterfly species. However, at a dose of 0.02 mg/plant,P. rapae preferred the cabbage extract whereasP. napi oleracea still preferred the (2R)-glucobarbarin. No such difference in response of the two species to the same two concentrations of (2S)-glucobarbarin was obtained. The results indicate a distinct difference in sensitivity of these butterflies to the epimers of glucobarbarin, and the differences in behavioral responses of the two butterfly species depend to a large extent on the concentration of stimulant present. PMID- 24242066 TI - Chemical discrimination by tongue-flicking in lizards: A review with hypotheses on its origin and its ecological and phylogenetic relationships. AB - Tongue-flicking is a synapomorphy of squamate reptiles functioning to sample chemicals for vomerolfactory analysis, which became possible in primitive squamates when ducts opened from the vomeronasal organs to the roof of the mouth. Extant iguanian lizards in families that do not use the tongue to sample chemical prey cues prior to attack partially protrude it in two feeding contexts: during capture by lingual prehension and after oral contact with prey. These lizards do not exhibit strike-induced chemosensory searching. Lingual prey prehension is present in iguanian lizards and inSphenodon, the sister taxon of Squamata. During attempts to capture prey, the tongues of primitive squamates inevitably made incidental contact with environmental substrates bearing chemicals deposited by prey, conspecifics, and predators. Such contact presumably induced selection for tongue-flicking and ability to identify biologically important chemicals. Most iguanian lizards are ambush foragers that use immobility as a major antipredatory defense. Because tongue-flicking at an ambush post would not allow chemical search beyond the vicinity of the head and would render them easier for predators and prey to detect, typical iguanians tongue-flick neither while foraging nor to identify predators. They do detect pheromones by tongue-flicking. Scleroglossan lizards are typically active foragers that rely on speed to escape. Being freer to move the tongue, they have evolved lingual sampling allowing detection of chemical cues of conspecifics, predators, and prey, as well as strike-induced chemosensory searching, some can follow pheromone trails by tongue-flicking. Some families have lingual morphology and behavior specialized for chemosensory sampling. In varanids and snakes, the taxa showing the greatest lingual specialization, additional prey-related chemosensory behaviors have evolved. In iguanian and scleroglossan families that have secondarily adopted the foraging mode typical of the other taxon, prey chemical discrimination involving tongue flicking and strike-induced chemosensory searching are typical for the foraging mode rather than the taxon. Because foraging mode and state of prey chemical discrimination are stable within squamate families and to a large extent in higher taxa, both features have been retained from the ancestral condition in most families. However, in three cases in which foraging mode has changed from its ancestral state, the state of prey chemical discrimination has also changed, indicating that prey chemical discrimination is adaptively adjusted to foraging mode. Indeed, acquisition of lingually mediated prey chemical discrimination may have made feasible the evolution of active foraging, which in turn appears to have profoundly influenced the further evolution of squamate chemosensory structures and behavior, placing a selective premium on features enhancing the tongue's efficiency as a chemical sampling device. The advent of tongue-flicking to sample prey chemicals and thus detect hidden prey may have allowed generalist (cruise) or ambush foragers, if early squamates were such, to become specialists in active foraging. Alternatively, if the common ancestors of squamates were active foragers, the adoption of ambush foraging would have selected against participation of the tongue in locating prey. Acting jointly, tongue-flicking and active foraging have had momentous consequences for squamate diversification. Specialization for active foraging would appear to have had ramifying effects on antipredatory defenses, body form, territoriality, mating systems, and reproductive physiology. PMID- 24242068 TI - Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer. AB - Aromatase inhibitors are the major first-line treatment of estrogen receptor positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor alpha (ERalpha), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ERalpha, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ERalpha and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ERalpha and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. PMID- 24242069 TI - The transcription factor IRF8 counteracts BCR-ABL to rescue dendritic cell development in chronic myelogenous leukemia. AB - BCR-ABL tyrosine kinase inhibitors (TKI) have dramatically improved therapy for chronic myelogenous leukemia (CML). However, several problems leading to TKI resistance still impede a complete cure of this disease. IFN regulatory factor-8 (IRF8) is a transcription factor essential for the development and functions of immune cells, including dendritic cells. Irf8(-/-) mice develop a CML-like disease and IRF8 expression is downregulated in patients with CML, suggesting that IRF8 is involved in the pathogenesis of CML. In this study, by using a murine CML model, we show that BCR-ABL strongly inhibits a generation of dendritic cells from an early stage of their differentiation in vivo, concomitant with suppression of Irf8 expression. Forced expression of IRF8 overrode BCR-ABL (both wild-type and T315I-mutated) to rescue dendritic cell development in vitro, indicating that the suppression of Irf8 causes dendritic cell deficiency. Gene expression profiling revealed that IRF8 restored the expression of a significant portion of BCR-ABL-dysregulated genes and predicted that BCR-ABL has immune stimulatory potential. Indeed, IRF8-rescued BCR-ABL-expressing dendritic cells were capable of inducing CTLs more efficiently than control dendritic cells. Altogether, our findings suggest that IRF8 is an attractive target in next generation therapies for CML. PMID- 24242070 TI - Small-molecule intramimics of formin autoinhibition: a new strategy to target the cytoskeletal remodeling machinery in cancer cells. AB - Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics. In screening for DID-DAD disruptors that activate mDia, we identified two molecules called intramimics (IMM-01 and -02) that were sufficient to trigger actin assembly and microtubule stabilization, serum response factor mediated gene expression, cell-cycle arrest, and apoptosis. In vivo analysis of IMM-01 and -02 established their ability to slow tumor growth in a mouse xenograft model of colon cancer. Taken together, our work establishes the use of intramimics and mDia-related formins as a new general strategy for therapeutic targeting of the cytoskeletal remodeling machinery of cancer cells. PMID- 24242071 TI - Requirements for Aurora-A in tissue regeneration and tumor development in adult mammals. AB - Aurora-A is a kinase involved in the formation and maturation of the mitotic spindle and chromosome segregation. This kinase is frequently overexpressed in human cancer, and its activity may confer resistance to antitumoral drugs such as Taxol. Inhibition of Aurora-A results in mitotic defects, and this kinase is considered as an attractive therapeutic target for cancer. Nevertheless, the specific requirements for this kinase in adult mammalian tissues remain unclear. Conditional genetic ablation of Aurora-A in adult tissues results in polyploid cells that display a DNA-damage-like response characterized by the upregulation of p53 and the cell-cycle inhibitor p21(Cip1). This is accompanied by apoptotic, differentiation, or senescence markers in a tissue-specific manner. Therapeutic elimination of Aurora-A prevents the progression of skin and mammary gland tumors. However, this is not due to significant levels of apoptosis or senescence, but because Aurora-A-deficient tumors accumulate polyploid cells with limited proliferative potential. Thus, Aurora-A is required for tumor formation in vivo, and the differential response observed in various tissues might have relevant implications in current therapeutic strategies aimed at inhibiting this kinase in the treatment of human cancer. PMID- 24242072 TI - Putative role of a Streptomyces coelicolor-derived alpha-mannosidase in deglycosylation and antibiotic production. AB - SCO0948 was found to be the single open reading frame annotated to encode an alpha-mannosidase (AM1) in Streptomyces coelicolor M145. To characterize the protein, we overexpressed SCO0948 in Escherichia coli BL21(DE3). Recombinant AM1, with a molecular weight of 110 kDa, exhibited alpha-mannosidase activity toward 4 nitrophenyl-alpha-D-mannopyranoside with a K m of 4.61 mM, a V(max) of 101.6 mM/min, and a specific activity of 47.96 U/mg. Treatment of ovalbumin, a glycoprotein, with AM1 resulted in partial deglycosylation, as assessed by glycostaining and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The S. coelicolor deletion mutant for SCO0948 failed to produce alpha-mannosidase activity, confirming AM1 as the only alpha-mannosidase in S. coelicolor M145. Interestingly, the deletion mutant and a complementation strain produced lower levels of the antibiotics actinorhodin and undecylprodigiosin in glucose minimal media. The results indicate that AM1 as an alpha-mannosidase influences deglycosylation and antibiotic production in S. coelicolor M145. PMID- 24242073 TI - Antimicrobial properties of zeolite-X and zeolite-A ion-exchanged with silver, copper, and zinc against a broad range of microorganisms. AB - Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framework with cations, water within pores. Their cation contents can be exchanged with monovalent or divalent ions. In the present study, the antimicrobial (antibacterial, anticandidal, and antifungal) properties of zeolite type X and A, with different Al/Si ratio, ion exchanged with Ag(+), Zn(2+), and Cu(2+) ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of microorganisms including bacteria, yeast, and mold. It was observed that Ag(+) ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag(+), Zn(2+), and Cu(2+) ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required. PMID- 24242075 TI - Reproductive issues in adults with cystic fibrosis: Implications for genetic counseling. AB - This article reviews reproductive issues faced by the growing number of individuals with cystic fibrosis (CF) who reach adulthood. Approximately 97-98% of males with CF are infertile and they may have an increased risk for genitourinary anomalies. Females with CF may experience delayed puberty, irregular menstrual cycles, and decreased fertility. Women with CF who have good clinical scores, good nutritional status, and normal lung volumes with mild to moderate airway obstruction, have a better chance for successful pregnancies. The role of the genetic counselor in counseling adults with CF is discussed and resources for CF adults are provided. PMID- 24242074 TI - Mitochondrial enhancement for neurodegenerative movement disorders: a systematic review of trials involving creatine, coenzyme Q10, idebenone and mitoquinone. AB - BACKGROUND: Neurodegenerative movement disorders mainly include Parkinson's disease (PD), atypical parkinsonisms, Huntington's disease (HD), and Friedreich's ataxia (FA). With mitochondrial dysfunction observed in these diseases, mitochondrial enhancement such as creatine, coenzyme Q10 (CoQ10) and its analogues (idebenone and mitoquinone) has been regarded as a potential treatment. AIM: In this paper, we systematically analysed and summarized the efficacy of mitochondrial enhancement in improving motor and other symptoms in neurodegenerative movement disorders. METHODS: We searched the electronic databases PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure until September 2013 for eligible randomized controlled trials (RCTs), as well as unpublished and ongoing trials. We calculated the mean differences for continuous data with 95% confidence intervals and pooled the results using a fixed-effect model, if no significant statistical heterogeneity was found (I(2) < 50%). RESULTS: We included 16 studies with 1,557 randomized patients, which compared creatine, CoQ10 or its analogues with placebo in motor and other symptoms. No significant improvements were found in the motor symptoms of PD, atypical parkinsonisms or HD patients, while only the high dose of idebenone seems to be promising for motor improvement in FA. Certain benefits are found in other symptoms. CONCLUSIONS: There is insufficient evidence to support the use of mitochondrial enhancement in patients with neurodegenerative movement disorders. More well-designed RCTs with large samples are required for further confirmation. PMID- 24242076 TI - Genetic counselor as a member of an outreach education team. AB - As part of a program to improve maternal and infant health in New Jersey, the Robert Wood Johnson Foundation has funded seven regional consortia throughout the State. One of the goals of the Northern New Jersey Regional Consortium is to provide a comprehensive educational program for ambulatory care staff. An outreach education team was established that includes a perinatal nurse educator, a neonatal nurse educator, a nutritional counselor and a genetic counselor. Many issues in genetics can be initially addressed by the ambulatory care provider. A good understanding and awareness of the impact of genetic issues in patient care is needed to enhance the ability to recognize patients needing special services. Early assessment of possible risk for developmental disabilities can lead to appropriate comprehensive care and improved pregnancy outcome. Regular in-service programs, addressing the way heredity contributes to developmental disorders, the latest techniques used in genetics and the available management programs, can be provided. The present study is an evaluation of the effectiveness of the program. PMID- 24242077 TI - Preconceptional family health evaluation: A regional education program for family planning clients and health professionals. AB - The Preconceptional Family Health Evaluation Program was a regional project developed and funded for 2 years by the New England Regional Genetics Group (NERGG) to educate family planning health professionals about genetics, and to offer family planning clients preconceptional identification of genetic and environmental exposure risks. To meet these goals, genetic education was provided on a regional basis to 45 family planning professionals. A self-administered family health risk questionnaire adaptable to individual family planning settings was developed. Five hundred and twenty-nine family planning clients voluntarily completed the questionnaire. Cigarette smoking (35%) and alcohol use (57%) were two major categories of risks identified. The Preconceptional Family Health Evaluation Program was well received by all participants and provided an effective means for regional education of family planning health professionals. As a result of the program, state program planners, clinical genetics services, and family planning health professionals developed a strong relationship that will serve future educational and genetic risk screening efforts. PMID- 24242078 TI - The utilization of genetic counselors within a newborn screening program. AB - Genetic counselors have participated in the Michigan Newborn Screening Program on a contractual basis since 1988. Their role includes newborn screening education and training, newborn nursery site visits, and monitoring newborn screening in hospitals. Their impact has been to improve the quality of newborn screening services by reducing errors and increasing completion of data fields on newborn screening cards, improving hospital nursery cooperation and problem solving, and enhancing health department response to specific problems. PMID- 24242079 TI - An educational program to overcome language and cultural barriers to genetic services. AB - Providing genetic services to families who do not speak English and whose cultures are quite diverse presents a unique challenge to genetic specialists. One approach that is being employed successfully is the use of specially trained genetic assistants to provide outreach, case finding, referral, support, interpretation, advocacy, and follow-up counseling. A basic genetic assistant training program for five bicultural/bilingual Southeast Asian case managers is described. The course syllabus can be used to train health workers who represent a variety of cultures and languages. PMID- 24242080 TI - Use of fuzzy logic models for prediction of taste and odor compounds in algal bloom-affected inland water bodies. AB - Mechanistic modeling of how algal species produce metabolites (e.g., taste and odor compounds geosmin and 2-methyl isoborneol (2-MIB)) as a biological response is currently not well understood. However, water managers and water utilities using these reservoirs often need methods for predicting metabolite production, so that appropriate water treatment procedures can be implemented. In this research, a heuristic approach using Adaptive Network-based Fuzzy Inference System (ANFIS) was developed to determine the underlying nonlinear and uncertain quantitative relationship between observed cyanobacterial metabolites (2-MIB and geosmin), various algal species, and physical and chemical variables. The model is proposed to be used in conjunction with numerical water quality models that can predict spatial-temporal distribution of flows, velocities, water quality parameters, and algal functional groups. The coupling of the proposed metabolite model with the numerical water quality models would assist various utilities which use mechanistic water quality models to also be able to predict distribution of taste and odor metabolites, especially when monitoring of metabolites is limited. The proposed metabolite model was developed and tested for the Eagle Creek Reservoir in Indiana (USA) using observations over a 3-year period (2008-2010). Results show that the developed models performed well for geosmin (R (2) = 0.83 for all training data and R (2) = 0.78 for validation of all 10 data points in the validation dataset) and reasonably well for the 2-MIB (R (2) = 0.82 for all training data and R (2) = 0.70 for 7 out of 10 data points in the validation dataset). PMID- 24242081 TI - Spatial pattern assessment of river water quality: implications of reducing the number of monitoring stations and chemical parameters. AB - The Tamsui River basin is located in Northern Taiwan and encompasses the most metropolitan city in Taiwan, Taipei City. The Taiwan Environmental Protection Administration (EPA) has established 38 water quality monitoring stations in the Tamsui River basin and performed regular river water quality monitoring for the past two decades. Because of the limited budget of the Taiwan EPA, adjusting the monitoring program while maintaining water quality data is critical. Multivariate analysis methods, such as cluster analysis (CA), factor analysis (FA), and discriminate analysis (DA), are useful tools for the statistically spatial assessment of surface water quality. This study integrated CA, FA, and DA to evaluate the spatial variance of water quality in the metropolitan city of Taipei. Performing CA involved categorizing monitoring stations into three groups: high-, moderate-, and low-pollution areas. In addition, this categorization of monitoring stations was in agreement with that of the assessment that involved using the simple river pollution index. Four latent factors that predominantly influence the river water quality of the Tamsui River basin are assessed using FA: anthropogenic pollution, the nitrification process, seawater intrusion, and geological and weathering processes. We plotted a spatial pattern using the four latent factor scores and identified ten redundant monitoring stations near each upstream station with the same score pattern. We extracted five significant parameters by using DA: total organic carbon, total phosphorus, As, Cu, and nitrate, with spatial variance to differentiate them from the polluted condition of the group obtained by using CA. Finally, this study suggests that the Taiwan EPA can adjust the surface water-monitoring program of the Tamsui River by reducing the monitoring stations to 28 and the measured chemical parameters to five to lower monitoring costs. PMID- 24242082 TI - Long-term results of probing guided with soft cannula in children with congenital nasolacrimal duct obstruction. AB - PURPOSE: To report the results of soft probing in children with congenital nasolacrimal duct obstruction (CNLDO). MATERIALS AND METHODS: A prospective, non randomised interventional study included 158 eyes of 122 children aged 2 months-5 years, with CNLDO. A plastic intravenous catheter sheath supported intraluminally with a guiding metal probe was introduced through the superior canaliculus. During intubation, the plastic cannula was gently introduced through the nasolacrimal system, while the metal probe inside was withdrawn concurrently. After the complete withdrawal of the metal probe, the duct was irrigated with a high pressure saline solution through the plastic cannula. Once the obstruction was totally dissolved and a patent passage was observed, the plastic cannula was withdrawn and the procedure was completed with a nasolacrimal lavage with a gentamycin and dexamethasone combination. RESULTS: Clinically successful results were achieved in 142 eyes (89.8 %). No significant complications occured intraoperatively or postoperatively. CONCLUSIONS: In children under age 5, our technique has a high success rate with no significant complications. This method allows probing in a more controlled way. This method may be particularly suitable for surgeons during training, when the most false lumen formation is observed. PMID- 24242083 TI - Space-charge-dominated mass spectrometry ion sources: Modeling and sensitivity. AB - The factors determining the sensitivity of space-charge-dominated (SCD) unipolar ion sources, such as electrospray (ESP) and corona atmospheric pressure ionization (API) have been studied theoretically. The most important parameters are the ion density and ion drift time in the vicinity of the sampling orifice. These are obtained by solving a system of differential equations, "the space charge problem." For some simple geometries, analytical solutions are known. For a more realistic "needle-in-can" geometry, a solution to the space-charge problem was obtained using a finite-element method. The results illustrate some general characteristics of SCD ion sources. It is shown that for typical operating conditions the minimum voltage required to overcome the space-charge effect in corona API or ESP ion sources constitutes a dominant or significant fraction of total applied voltage. Further, the electric field and the ion density in the region of the ion-sampling orifice as well as the ion residence time in the source are determined mainly by the space charge. Finally, absolute sensitivities of corona API ion sources were calculated by using a geometry-independent treatment of space charge. PMID- 24242084 TI - Selective ion isolation/rejection over a broad mass range in the quadrupole ion trap. AB - Techniques are presented for mass-selective ion manipulation over a wide mass range in a three-dimensional quadrupole. The methods use an auxiliary, low amplitude radio-frequency signal applied to the endcap electrodes. This signal is either held at a single frequency as the fundamental radio-frequency trapping amplitude is ramped or swept over a frequency range while the fundamental radio frequency trapping amplitude is held at a fixed level. Ion isolation and ejection are demonstrated for ions formed within the ion trap using electron ionization and for ions injected into the ion trap formed either by an air-sustained glow discharge or by electrospray. Mass-selective ion ejection is used to reduce matrix-ion-induced space charge during ion injection, thereby producing signal enhancement for the detection of 2, 4, 6-trinitrotoluene in air. Mass-selective isolation of ions with mass-to-charge ratios above the normal operating range (m / z 650) for the ion trap is also demonstrated after injection of myoglobin ions formed via electrospray. PMID- 24242085 TI - Investigation of UV matrix-assisted laser desorption fourier transform mass spectrometry for peptides. AB - Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA Ultraviolet matrix-assisted laser desorption can be used to enhance formation of [M + H](+), [M + Na](+), and [M + K)(+) ions from small peptides for Fourier transform mass spectrometry (FTMS). In accord with laser desorption (LD) time-of-flight experiments, matrices such as nicotinic acid and 2 pyrazinecarboxylic acid exhibit strong enhancement effects (i.e., formation of abundant protonated and cationized molecules for the analyte with virtually no fragment ions) for 266 nm LD/FTMS, whereas pyrazinedicarboxylic acid provides no matrix enhancement at this wavelength. Both sinapinic acid and coumarin-120 provide strong matrix enhancement effects for the 355-nm LD of peptides. For the small peptides examined in this study, no significant differences in the abundance of fragment ions were observed between the 266- and 355-nm wavelengths. Matrix-assisted LD/FTMS is useful for the generation and characterization of ions corresponding to protonated and cationized molecules from virtually all biological compounds with molecular weights up to 2000. The lack of observation of biological ions with m/ z > 2500 may be related to inefficient trapping of these laser-desorbed ions or instrumental detection limitations of FTMS and is under further investigation. PMID- 24242086 TI - Small molecules as substrates for adsorption/desorption in (252)CF plasma desorption mass spectrometry. AB - Department of Chemistry, Texas A & M University, College Station, Texas, USA We present a new approach to substrate selection for californium-252 plasma desorption mass spectrometry ((252)Cf_PDMS) in which small volatile molecules that are water insoluble are used as matrices in place of the polymeric substrates used in previous studies. The desirable features of analyte adsorption are combined with the concept of using a volatile matrix to reduce the level of internal excitation of a desorbed analyte and to assist in ionization during the desorption process. Derivatives of anthracene were found to meet these requirements and to perform satisfactorily as substrates in (252)Cf-PDMS. Spectra were obtained for bovine insulin (m I z 5734) adsorbed onto 9-anthroic acid and 2 aminoanthracene and compared with spectra using a nitrocellulose substrate. Sharper peaks and lower backgrounds are observed when the 9-anthroic acid matrix is used, indicating reduced levels of internal excitation and initial kinetic energy for the desorbed molecular ion of insulin. A comparison of the performance of 9-anthroic acid and 2-aminoanthracene shows the influence of substrate functional groups on desorbed protein yields. Finally, the versatility of the small-molecule matrix concept is discussed with respect to selection of a range of functionality, solubility, and hydrophilicity. PMID- 24242087 TI - Solution chemistry and secondary ion emission from amine-glycerol solutions. AB - Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA Secondary ion mass spectra were obtained from a series of C4-C10 n alkylamines introduced via the gas phase onto glycerol. It was found that the amine-characteristic secondary ion intensity varied linearly with amine partial pressure. Henry's law constants and surface activity constants for each of the amines in glycerol solution were measured. A linear correlation was found between amine-characteristic secondary ion intensity and Henry's law concentrations. The concentrations calculated from Henry's law were too low to yield the intensities observed, indicating that secondary ion precursors were not free-base amine molecules but ions in solution. Explicit kinetic equations describing glycerol and amine protonation and deprotonation as a result of primary ion damage to the solutions are derived to rationalize the observed spectra. PMID- 24242088 TI - Molecular species analysis of arachidonate containing glycerophosphocholines by tandem mass spectrometry. AB - Carboxylate anions arising from collision-induced dissociation (CID) of the [M - 15](-) ion produced by fast atom bombardment (FAB) of glycerophosphocholine (GPCho) were previously shown to be produced in an abundance ratio of 1:3 for the carboxylic acids esterified at sn - 1 and sn - 2, respectively. This observation has been confirmed in a series of 13 synthetic GPCho molecular species. A good correlation was found between the isomeric purity of GPCho molecular species as determined by negative-ion FAB/CID analysis and the isomeric purity of the sn - 2 fatty acid using a phospholipase A2 assay. Negative-ion FAB mass spectra of several 1-0-alkyl-2-acyl-GPCho molecular species were found to be similar to those of diacyl GPCho. However, the cm spectra from the major high-mass ions are different from those of the diacyl species in that the [M - 15](-) ion yields only one carboxylate anion and the [M - 86](-) undergoes a neutral loss of the sn - 2 carboxylic acid as a major decomposition product. These results suggest several rules useful for structural characterization of GPCho molecular species by negative-ion tandem mass spectrometry (MS/MS): (1) For diacyl species, the mass of the two carboxyl anions plus the mass of the GPeho backbone (minus a methyl group) must correspond to the mass of the [M - 15] anion; (2) for diacyl species there is a carboxylate anion ratio approximately 1:3 for the substituents at sn - 1 and sn - 2; and (3) for alkylether species, only one fatty acyl group is present, and the difference between the [M - 15] ion and the GPCho backbone (minus methyl) plus the fatty acyl group at sn - 2 corresponds to an alkylether substituent. (4) Assignment of ether-linked molecular species can be made from the [M - 86](-) ion, which has a strong neutral loss of the sn - 2 fatty acid.Analysis of GPCho isolated from human neutrophils by total lipid extraction and normal-phase HPLC was carried out by negative-ion FABand MS/MS. The major arachidonate-eontaining molecular species, which comprise only 5% of total GPCho, were identified by using precursor ion scans for the arachidonate anion, m/ z 303. Decomposition of identified. precursor ions permitted the assignment of those molecular species of GPCho that contain arachidonate at sn - 2 and identification of the substituent at the sn - 1 position. These results were compared to previously identified molecular species from human neutrophils. Several minor arachidonate-containing molecular species were tentatively identified. PMID- 24242089 TI - Multiple scan modes in the hybrid tandem mass spectrometric screening and characterization of the glutathione conjugate of 2-furamide. AB - The glutathione conjugate of 2-furamide has been screened for and structurally characterized by tandem mass spectrometry (MS(MS) by using a hybrid instrument of BEqQ design. Mass spectrometry experiments employed fast atom bombardment (FAB) ionization of a crude bile extract from a rat dosed with a 1:1 mixture of unlabeled and [ (13)C12-furamide. Initial screening for glutathione conjugates employed constant neutral loss scanning to detect the loss of 129 u, corresponding to the loss of the gamma-glutamyl moiety of the conjugates. By direct comparison with control bile, [M + H] (+) ions of m/z 417 and 418 were readily identified as candidate ions corresponding to the glutathione conjugates of unlabeled and (13)C-labeled 2-furamide. Complementary screening information was generated by using a methylated bile extract, with constant neutral loss scanning to detect the loss of the methylated gamma-glutamyl moiety (143 u). An alternative screening procedure employing parent ion scanning to detect the sodium adducts of methylated glutathione conjugates was also developed. Structural information was generated by frrst-generation product ion scanning of the protonated and sodium cationized forms of the candidate species, both native and derivatized. This provided a body of internally consistent evidence that the conjugate retains the pseudoaromatic furan ring system without ring hydroxylation. The utility of sequential mass spectrometry (MS(MS(MS) capability of the hybrid instrument in the analysis of complex biological mixtures was also demonstrated. Using the bile extract, first-generation product ions that formed in either the first or second field-free region of the double-focusing portion of the instrument were subsequently collisionally activated in the rf-only quadrupole followed by mass analysis of the second-generation product ions. Structural information so provided for the glutathione conjugate of 2-furamide further substantiated its retention of the pseudoaromatic furan ring system and facilitated plausible assignment of structures to ionic species generated through multiple decomposition events. PMID- 24242090 TI - Sequential ortho effects: characterization of novel [M - 35](+) fragment ions in the mass spectra of 2-alkyl-4, 6-dinitrophenols. AB - High-resolution mass spectrometry (HRMS), hybrid tandem mass spectrometry (MS/MS) (EBqQ), and photoelectron-photoion coincidence (PEPICO) experiments were conducted to examine a possible ortho-ortho effect resulting in a novel [M - 35](+) fragment ion in 2-alkyl-4, 6-dinitrophenols. For compounds having ethyl or larger alkyl substituents, [M35](+) was observed only when [M - 18](+) ions were present, with the ortho nitro group being involved in the reaction to [M- 35](+). For [M - 18](+) and [M - 35](+), HRMS results were consistent with losses of H2O and H2O + OH, respectively, whereas MS/MS results indicated a sequential reaction due to metastable dissociations. The appearance energy determined by PEPICO for [M - 35](+) was found to be greater than the appearance energy for [M - 18](+), thus supporting a sequential reaction. 69-75). PMID- 24242091 TI - Cluster ions ejected from an Li-Mg alloy liquid metal ion source: Observation of MG 2 (2+) and MG 3 (2+). AB - Ions ejected from a liquid metal ion source of an Li-Mg (10 atom %) alloy have been investigated by using a magnetic mass analyzer. In addition to singly charged homonuclear Li n (+) (n <= 9) and Mg n (+) (n <= 4) and heteronuclear MgmLi n (+) (m, n <= 2) clusters, doubly charged diatomic and triatomic Mg clusters are observed. Discussion is focused on the observability and the formation mechanism of the doubly charged small Mg clusters. A postionization process is suggested for the formation of the doubly charged clusters. PMID- 24242092 TI - A particulate isotopic standard of plutonium in an aluminosilicate matrix. AB - Plutonium isotopic microstandard particles have been produced for mass spectrometer calibration. The particles may also be useful as an elemental standard for calibration of electron and ion microprobe instruments. The standard consists of spherical, micrometer-size aluminosilicate particles loaded with plutonium of known isotopic distribution. The morphology, elemental composition, and plutonium isotopic composition of the particles have been characterized. PMID- 24242093 TI - Isotope dilution gas chromatography/mass spectrometry for platinum determination in urine. AB - The therapeutic importance of platinum (Pt) compounds, the growing accessibility of gas chromatography/mass spectrometry (GC/MS) systems in clinical laboratories, and the lack of a mass spectrometric method for the determination of Pt in biological samples motivated us to develop an isotope dilution GC/MS assay for Pt. The method is based on the use of lithium bis(trifluoroethyl) dithiocarbamate, Li(FDEDTC), as a chelating agent and enriched (192)Pt for isotope dilution. Conditions were optimized for the precise and accurate determination of isotope ratios of Pt by using a 10-m DB-l fused silica capillary column and a reverse-geometry double-focusing mass spectrometer with selected ion monitoring. An overall precision of 1% was obtained by combining within-run precision and between-run precision at the 10-ng level. No appreciable memory effect was observed when samples with different isotope ratios were analyzed sequentially. The method was validated by the quantitation of Pt in National Institute of Standards and Technology freeze-dried urine sample SRM 2670. A concentration value of 125 +/- 6 /Lg/L (n = 6) was obtained by using four different sets of isotope ratios in the molecular ion and supports the National Institute of Standards and Technology recommended value of 120 +/- ? MUg/L. Limits-of-quantitation, estimated at 3 MUg/L, are made possible by the high sensitivity of the method and the low blank value for Pt. PMID- 24242094 TI - Detection of femtomole and sub-femtomole levels of peptides by tandem magnetic sector/reflectron time-of-flight mass spectrometry and matrix-assisted laser desorption ionization. AB - This article describes results of low-level (sub-femtomole) detection of peptides by matrix-assisted laser desorption ionization. The matrix-assisted laser desorption ionization method can be used for low-level detection of the parent ion, either [M + H](+) or [M + Na](+), and collision-induced dissociation of the parent ion can be performed at the picomole level. The instrument used for these studies is a novel high-performance magnetic sector (electric(E)/magnetic(B) sector)/reflectron time-of-flight (TOP) tandem mass spectrometer (EB/TOF). PMID- 24242096 TI - A twist in the FOXO tale: edging closer to revealing the secrets of unlimited tissue renewal. PMID- 24242098 TI - Connecting the dots between G proteins, G protein coupled receptors, and neuronal nicotinic acetylcholine receptors (Comment on DOI 10.1002/bies.201300082). PMID- 24242099 TI - Rearranging senescence: transposable elements become active in aging cells (Comment on DOI 10.1002/bies.201300097). PMID- 24242100 TI - Ceci n'est pas une DNMT: recently discovered functions of DNMT2 and their relation to methyltransferase activity (Comment on DOI 10.1002/bies.201300088). PMID- 24242105 TI - Neurogenesis: a new journal feature. PMID- 24242106 TI - Electrophysiological and field activity of halogenated analogs of (E,E)-8,10 dodecadien-1-ol, the main pheromone component, in codling moth (Cydia pomonella L.). AB - Pest monitoring and control of the codling moth,Cydia pomonella L., have been developed using the main pheromone component of this species, (E,E)-8,10 dodecadienol (codlemone). However, the activity of codlemone is not satisfactory for pest control by mating disruption. Thus, we have synthesized halogenated analogs of codlemone to see if they could be used as new agents for pest control of the codling moth. Their biological activity was measured by electrophysiological techniques. In EAG screening, codlemone was the most active compound. F(10,11)-codlemone [(E,E)-10,11-difluoro-8,10-dodecadienol] and Cl codlemone [(E,E)-11-chloro-8,10-undecadienol] elicited significant EAG responses, F(10,11)-codlemone triggering responses not significantly different from responses to codlemone. EAG cross-adaptation experiments and single sensillum recordings revealed that these compounds were detected by the same receptor neuron type as codlemone. No competitive inhibition with codlemone was observed from nonactive compounds. In field trapping, F(10,11)-codlemone and Cl-codlemone were more attractive to male codling moths than codlemone itself. Possible explanations of this activity are discussed. PMID- 24242107 TI - Aggregation pheromone of palmetto weevil,Rhynchophorus cruentatus (F.) (Coleoptera: Curculionidae). AB - 5-Methyl-4-octanol is the major aggregation pheromone of the palmetto weevil,Rhynchophorus cruentatus (F.). The pheromone (cruentol) was identified by coupled gas chromatographic-electroantennographic (GC-EAD) analysis of male produced volatiles, coupled GC-mass spectrometry (MS) in electron impact and chemical ionization mode, and coupled GC-high resolution MS. In laboratory and field assays, a diastereomeric mixture of synthetic cruentol greatly enhanced attraction of weevils to cabbage palmetto,Sabal palmetto (Walter), stem tissue, indicating that cruentol and host volatiles are synergistically attractive. An attractive lure in combination with efficient traps should facilitate development of semiochemical-based management forR. cruentatus. PMID- 24242108 TI - Inhibition of potato cyst nematode hatch by lignans fromBupleurum salicifolium (Unbelliferae). AB - A series of lignans fromBupleurum salicifolium Soland (Umbelliferae) were tested for nematostatic activity on the cysts and freed secondstage juveniles of the potato cyst nematodesGlobodera rostochiensis andG. pallida. None of the six lignans tested-bursehernin, matairesinol, syringaresinol, the novel product buplerol, guayarol, and a derivative, nortrachelogenin triacetate-showed nematicidal activity in an in vitro analysis with second-stage juveniles, but significant differences were noted when the lignans were assayed for nematostatic activity as cyst hatching inhibitors. Bursehernin and matairesinol showed the greatest activity, at concentrations of 50 ppm. This is the first known instance of a natural product inhibiting the hatch of the nematodeG. pallida. The HID (hatching inhibiting dose) of bursehernin was estimated, and some conclusions were drawn about the structure-activity relationships of the lignans under study. PMID- 24242109 TI - Stratospheric ozone depletion and plantinsect interactions: Effects of UVB radiation on foliage quality ofCitrus jambhiri forTrichoplusia ni. AB - Projected decreases in stratospheric ozone may result in increases in shortwave ultraviolet (UVB) irradiation at the earth's surface. Furanocoumarins, phototoxic compounds found inCitrus jambhiri foliage, increase in concentration when these plants are grown under enhanced UVB. Survivorship schedules ofTrichoplusia ni (Lepidoptera: Noctuidae) caterpillars reared on plants in the presence and absence of enhanced UVB regimes differ significantly; larvae develop more slowly in early life when reared on plants exposed to increased UVB. This same developmental pattern is observed whenT. ni larvae are reared on artificial diets amended with ecologically appropriate amounts of furanocoumarins. Thus, anthropogenically derived changes in stratospheric ozone and concomitant changes in UV light quality at the earth's surface may influence ecological interactions between insects and their host plants by altering secondary metabolism and hence foliage quality for herbivores. PMID- 24242110 TI - Toward the chemical ecology of medicinal plant use in chimpanzees: The case ofVernonia amygdalina, a plant used by wild chimpanzees possibly for parasite related diseases. AB - The bitter and related constituents have been isolated fromVernonia amygdalina (Compositae), a plant ingested by wild chimpanzees possibly suffering from parasite-related diseases in the Mahale Mountains National Park, Tanzania. Isolated from the plant were four known sesquiterpene lactones, seven new steroid glucosides, and two aglycones of the glucosides. The sesquiterpene lactones showed significant in vitro antischistosomal, plasmodicidal, and leishmanicidal activities. Antischistosomal activity was also found for the major steroid glucoside, vernonioside B1. A trend in the glucosides to show significant antischistosomal, plasmodicidal, and amebicidal activities when the sugar moiety was removed, was observed. Vernodalin, judged as the most significant constituent for antiparasitic activities in vitro, was tested for in vivo antischistosomal effect. It was, however, highly toxic to the cercaria-infected mouse. Chimpanzees have been only rarely observed to ingest anything but the pith of the young stem. The occurrence of vernonioside B1 and its aglycone vernoniol B1, the major constituents among the steroid-related constituents, were detected at significant levels in the pith. However, vernodalin was abundant only in the leaves and bark. Thus, chimpanzees at Mahale were hypothesized to control parasite-related diseases by ingesting the young pith of this tree containing steroid-related constituents. PMID- 24242111 TI - Production of cardenolides versus sequestration of pyrrolizidine alkaloids in larvae ofOreina species (Coleoptera, Chrysomelidae). AB - Adult leaf beetles of the genusOreina are known to be defended either by autogenously produced cardenolides or by pyrrolizidine alkaloids (PAs) sequestered from the food plant, or both. In this paper we analyze larvae of differentOreina species and show that the larvae contain the same defensive toxins as the adults in quantities similar to those released in the adults' secretion. Both classes of toxins are found in the body and hemolymph of the larvae, despite their different origins and later distribution in the adults. Larvae of sequestering species differed in their PA patterns, even though they fed on the same food plants. The concentration in first-instar larvae of a PA sequestering species was similar to that in fourth-instar larvae. In all stages examined, the amount of PAs per larva did not greatly exceed the estimated uptake of one day. Eggs of two oviparous species contained large concentrations of the adult's toxins, while neonates of a sequestering larviparous species had no PAs. PMID- 24242112 TI - Trans-ceralure isomers: Differences in attraction for mediterranean fruit fly,Ceratitis capitata (Wied.) (diptera: Tephritidae). AB - Differences in attractiveness of four individualtrans isomers of ceralure (CRL) [ethyl 4- (and 5-) iodo-trans-2-methylcyclohexane-1-carboxylate] for male Mediterranean fruit fly,Ceratitis capitata (Wiedemann), were investigated. One of the isomers, CRL-B1 (ethylcis-5-iodo-trans-2-methylcyclohexane-1-carboxylate) was significantly superior to the three othertrans-CRL isomers, CRL, trimedlure (TML) [1,1-dimethylethyl 4- (and 5-) chloro-trans-2-methylcyclohexane-1-carboxylate], and TML-C (1,1-dimethylethyl-cis-4-chloro-trans-2-methylcyclohexane-1 carboxylate) on an equal weight basis. PMID- 24242113 TI - Field tests of syntheticManduca sexta sex pheromone. AB - In field experiments traps were baited with live females or with a two-, four-, or eight-component blend of the 16-carbon aldehydes previously identified as components of the sex pheromone emitted by femaleManduca sexta moths. The blends were formulated on rubber septa. Traps baited with a blend of all eight aldehydes captured moreM. sexta males than any other treatment. Septa loaded with 600 MUg of the eight-component blend were attractive to males for about seven days in the field. Septa loaded with the eight-component blend and stored in a refrigerator at 4 degrees C for a year released the conjugated diene and triene aldehydes at the same rate as freshly prepared septa and were equally attractive in the field. PMID- 24242114 TI - An automated system for use in collecting volatile chemicals released from plants. AB - A system is described for the collection of volatiles produced by plants that minimizes stress on the plant in an environment that is free from chemical impurities. Air entering a volatile collection chamber containing a plant is purified using a nonwoven fabric media infused with charcoal. A multitasking, computer-automated system is described that can simultaneously collect volatilized chemicals from plants as well as monitor and record environmental conditions associated with those collections. Collection of up to 16 samples can be made in varying sampling order, flow rates, and user-specified time periods, without disturbing the sampling environment. During the same time period, this system is capable of simultaneously monitoring up to eight environmental parameters using any type of sensor with electrical signal outputs. A multiport base assembly was designed to fit around the base of the plant permitting air samples to be collected at the bottom of the chamber. The chamber can pass ambient light so the plant may follow its natural photocycles. The entire system can be configured for continuous laboratory duty or portable field use by utilizing components that run on DC voltages. For the purpose of testing the system's performance, we determined the periodicity of the release of volatiles from red and yellow flowering four o'clock plants,Mirabilis jalaba (Nyctaginaceae). The major chemical released from four o'clocks was identified as ocimene. The onset of release occurred between 1400 and 1600 hr and increased with time with maximum amount of ocimene released during 1800-2000 hr, followed by a decrease in emission. No ocimene was detected after 2400 hr. Determination of the amount of ocimene released per flower was calculated for the 1800- to 2000 hr time period. Based on the number of open flowers during the 1800- to 2000-hr period, yellow four o'clock's released 80.9 (+/-7.3 SD) ng/hr/flower, while the red flowers released 51.9 (+/-7.0 SD) ng/hr/flower. PMID- 24242115 TI - How goats learn to distinguish between novel foods that differ in postingestive consequences. AB - To better understand some of the mechanisms that control selection of novel foods differing in postingestive consequences, we offered goats current season's (CSG) and older (OG) growth twigs from the shrub blackbrush (Coleogyne ramosissima). CSG is higher than OG in nitrogen (1.04% v. 0.74%) and it is more digestible in vitro in goat rumen fluid (48% v. 38%). Nevertheless, goats acquire a preference for OG because CSG contains much higher levels of a condensed tannin that causes a learned food aversion. When CSG and OG were offered to goat naive to blackbrush, the goats did not choose either OG or CSG exclusively, but when they finally (1) ate more CSG than OG within a meal (averages of 44 g and 16 g, respectively) and (2) ate enough CSG within the meal to acquire an aversion (average of 44 g), they ingested less CSG than OG from then onward. Accordingly, the change in food selection resulting from postingestive feedback was influenced by the amount of each food ingested within a meal. This was further shown when we varied the amounts of CSG and OG that goats ingested within a meal, and then gave them by gavage the toxin lithium chloride (LiCl). They subsequently ate less of the food eaten in the greatest amount, regardless of whether it was CSG or OG. The salience of the flavor (i.e., taste and odor) of CSG and OG also played a role in the acquired aversion to CSG. Salience evidently was due to a flavor common to both OG and CSG that was more concentrated in CSG. We conclude that the relative amounts of different foods ingested within a meal, and the salience of the flavors of those foods, are both important variables that cause goats to distinguish between novel foods that differ in postingestive consequences. PMID- 24242116 TI - Response of male eye-spotted bud moth,Spilonota ocellana (Lepidoptera: Tortricidae), to different pheromone blends in north America and The Netherlands. AB - Response of male eye-spotted bud moth,Spilonota ocellana (Denis and Schiffermuller), to different ratios of synthetic sex pheromone components, (Z)-8 tetradecenyl acetate (Z8-14:OAc) and (Z)-8-tetradecenyl alcohol (Z8-14:OH), were compared in four North American locations and in one location in The Netherlands. In British Columbia, Nova Scotia, Michigan, and The Netherlands, a 99:1 blend ofZ8-14:OAc andZ8-14:OH captured significantly more maleS. ocellana thanZ8-14:OAc alone or binary blends containing 10-50%Z8-14:OH. In Ontario, where population sizes were low compared to the other four locations, trends in trap catches were similar, and there was no indication that maleS. ocellana responded differently to the tested pheromone blends. A 99:1 blend ofZ8-14:OAc andZ8-14:OH should be most effective in pheromone-based control programs ofS. ocellana in North America and in The Netherlands. Our results confirm earlier studies that a 99:1 blend ofZ8-14:OAc andZ8-14:OH captures significantly more maleS. ocellana thanZ8-14:OAc alone. However, our finding that a 99:1 blend ofZ8-14:OAc andZ8-14:OH is significantly more attractive than binary blends containing 10-50%Z8-14:OH differs from previous findings in Germany and Switzerland. PMID- 24242117 TI - Effect of odor derived from lion faeces on behavior of wild rabbits. AB - A synthetic repellent derived from lion feces was tested in both pen and field bioassay trials. The chemical suppressed the feeding of rabbits on carrots for approximately one month. The application of the chemical to rabbit burrows under field conditions showed that it decreased rabbit numbers in the treated warrens and that this effect could still be detected after five months. It is suggested that this chemical could be a timely environmentally acceptable addition to the armamentarium of control measures required to reduce the recent increase in rabbit numbers occurring in Britain. PMID- 24242118 TI - Oxidative responses in soybean foliage to herbivory by bean leaf beetle and three cornered alfalfa hopper. AB - Variation in induced responses in soybean is shown to be dependent, in part, upon herbivore species. Herbivory by the phloem-feeding three-cornered alfalfa hopper caused increases in the activities of several oxidative enzymes including lipoxygenases, peroxidases, ascorbate oxidase, and polyphenol oxidase. Bean leaf beetle defoliation caused increased lipoxygenase activity, but had little effect upon peroxidase, polyphenol oxidase, ascorbate oxidase, or trypsin inhibitor levels in either field or greenhouse studies. In one field experiment, prior herbivory by the bean leaf beetle subsequently reduced the suitability of foliage to the corn earwormHelicoverpa zea. The contribution of these findings to emerging theories of insect-plant interactions is discussed. PMID- 24242119 TI - Potential role of lipoxygenases in defense against insect herbivory. AB - The potential role of the plant enzyme lipoxygenase in host resistance against the corn earwormHelicoverpa zea was examined. Lipoxygenase is present in most of the common host plants ofH. zea, with highest activity in the leguminous hosts such as soybean and redbean. Treatment of dietary proteins with linoleic acid and lipoxygenase significantly reduced the nutritive quality of soybean protein and soy foliar protein. Larval growth was reduced from 24 to 63% depending upon treatment. Feeding byH. zea on soybean plants caused damage-induced increases in foliar lipoxygenase and lipid peroxidation products. Larvae feeding on previously wounded plant tissue demonstrated decreased growth rates compared to larvae feeding on unwounded tissue. Midgut epithelium from larvae feeding on wounded tissues showed evidence of oxidative damage as indicated by significant increases in lipid peroxidation products and losses in free primary amines. The potential role of oxidative and nutritional stress as a plant defensive response to herbivory is discussed. PMID- 24242120 TI - Influence of mustelid semiochemicals on population dynamics of the deer mouse (Peromyscus maniculatus). AB - The influence of mustelid anal-gland compounds on population dynamics of the deer mouse (Peromyscus maniculatus) was investigated. Densities of deer mice were not found to be significantly different between treated and control areas. However, on average, numbers of deer mice were lower on treated areas following the July treatments of 1991 and 1992. Survival rates appeared to be lower and more erratic on treated than control areas in 1991; however, there were no statistically significant differences. Reproduction appeared to be unaffected by the odors. We concluded that deer mice did not display a behavioral response to weasel odors. We speculated that decreases in densities were owing to predation by weasels, which were attracted to the odors on treated sites. We also concluded that the use of weasel odors as a biological control method for voles (Microtus spp.) would likely have little impact on deer mice (a nontarget species). PMID- 24242121 TI - Plant virus-induced changes in aphid population development and temporal fluctuations in plant nutrients. AB - Cucurbita pepo plants were infected with zucchini yellow mosaic virus or maintained noninfected.Aphis gossypii, which transmits the virus, lived longer and produced more offspring on infected than on noninfected plants. On infected plants, the intrinsic rate of natural increase forA. gossypii increased with time after inoculation. In a similar experiment, concentrations of phloem sap nutrients, including free amino acids, total protein, and sugars from infected and noninfected plants were compared for 37 days after inoculation. Significant differences in levels of individual amino acids from phloem exudate between infected and noninfected plants were found, yet the concentration of total amino acids was not substantially different between infected and noninfected plants. Beginning four days after inoculation, the total protein content of phloem exudate generally was lower in infected plants than noninfected plants. Likewise, the total sugar content of phloem exudate from infected plants was lower than that of noninfected plants beginning nine days after inoculation. In contrast with the results from analyses of phloem exudate, foliage from infected plants had higher levels of almost all amino acids than noninfected foliage beginning nine days after inoculation. Concentrations of individual and total amino acids in infected foliage increased throughout the experimental period. Although no temporal effects were observed in the foliage sugar content for either individual or total sugars, starch content decreased with time in infected plants, while in noninfected plants, starch content remained level. PMID- 24242122 TI - Phthalide-based host-plant resistance toSpodoptera exigua andTrichoplusia ni inApium graveolens. AB - A chemical basis for the difference in suitability between two celeriac (Apium graveolens var.rapaceum) cultivars for the survival and growth ofSpodoptera exigua (Hubner) andTrichoplusia ni (Hubner) was identified as sedanenolide (3-n butyl-4,5-dihydro-isobenzofuranone). Sedanenolide was isolated using a bioassay driven extraction and purification procedure and was identified using several spectrometric methods. Foliar concentrations of sedanenolide were negatively correlated with larval performance and were significantly higher in the cultivar less suitable for larval survival and growth. Sedanenolide andBacillus thuringiensis Berliner acted additively in reducing larval growth when combined in artificial diets, a result that is consistent with previous studies in which the combined effect of host plant cultivar andB. thuringiensis on larval survival and growth were additive. PMID- 24242124 TI - Female sex pheromone components of jasmine mothPalpita unionalis (Lepidoptera: Pyralidae). AB - (E)-11-Hexadecenal and (E)-11-hexadecen-1-yl acetate were found in abdomen tip extracts from females of the jasmine mothPalpita unionalis (Hubn). The identification was based on capillary GC analyses, mass spectrometry, and laboratory and field tests. In laboratory bioassays, both components elicited a low level of upwind flight by males. The two components when tested separately in the field were inactive, but the blend of the two components at a ratio of (3:7) was highly attractive to males. Traps baited with 1 mg of the two-component blend were competitive to traps baited with five virgin females. The addition of Z isomers components reduced male capture. PMID- 24242123 TI - Caribbean fruit fly,Anastrepha suspensa (Loew), attraction to host fruit and host kairomones. AB - Extracts of 22 fruits were tested for their attractancy toAnastrepha suspensa (Loew), the Caribbean fruit fly. Box-orange, calamondin, carambola, cattley guava, loquat, and Surinam-cherry were about equal in attractiveness to males and females. Nine synthetic chemicals, including four found in box-orange ripe seed, were attractive to females. Five synthetic chemicals, including two in box-orange ripe seed, were attractive to males. Farnesol,alpha-phellandrene, and 3-carene were highest in attractiveness to both males and females. Females were more attracted than males to 12 synthetic chemicals. These data suggest that host chemicals serve as attractants and that female and male specific attractants and traps could be developed from host kairomone data. These data also suggest that the volatilization of chemicals from water may play an important role in kairomone biology. PMID- 24242125 TI - Tasting green leaf volatiles by larvae and adults of Colorado potato beetle,Leptinotarsa decemlineata. AB - Larvae and adults of the Colorado potato beetle,Leptinotarsa decemlineata (Say), are shown to have galeal gustatory cells that are highly sensitive to distillate of potato leaf extracts, (E)-2-hexen-1-ol, (E)-2-hexenal, and other saturated and unsaturated six-carbon alcohols. In larvae and adults, the sensory response patterns elicited by leaf homogenate, leaf distillate and a mixture of these two extracts differ in subtle ways. Beetle larvae feed most readily on Millipore disks treated with leaf homogenate and the mixture, but they did not feed on disks treated with leaf distillate. The differences in behavioral response and sensory input are used to derive a potential gustatory code that may stimulate different levels of feeding. This code may be disrupted by compounds present in nonhost leaves, thus leading to reduced feeding. Possible interactions of sapid leaf volatiles, amino acids, sugars, and potentially deterrent plant compounds are discussed. PMID- 24242126 TI - Use of conifer volatiles to reduce injury caused by carrot psyllid,Trioza apicalis, Forster (Homoptera, Psylloidea). AB - The feeding and oviposition of the carrot psyllid,Trioza apicalis, were reduced by the application of fresh spruce and pine sawdust along the seedling rows in carrot fields. Turpentine and separate monoterpene hydrocarbons, mixed into old sawdust and/or placed in polyethylene tubes, were also effective. At a dose of 0.5 liter/m, fresh sawdust reduced the damage to 18% of the plants, compared to 100% damage in untreated plants. The sawdust materials were spread on the soil surface at four- or seven-day intervals during the oviposition period. The tubes were placed along the carrot rows before the oviposition started. Turpentine and separate monoterpene hydrocarbons afforded a protective effect of the same order of magnitude as that obtained from fresh sawdust. The volatile profiles of the spruce and pine sawdust as well as of the turpentine used were determined. PMID- 24242127 TI - Responses of fig wasps to host plant volatile cues. AB - Fig wasps (Chalcidoidea; Agaonidae) are intimately associated with the 750 or so species of fig trees (Ficus, Moraceae). Each tree species is usually pollinated by a single species of wasp belonging to the subfamily Agaoninae, while other wasps of the family are parasitoids or seed predators. Previous experiments have shown that the wasps are attracted to the trees by volatiles emanating from the figs. Using fig-bearing trees and arrays of sticky traps baited with figs, we investigated the specificity of wasp attraction and its timing. The pollinators of two closely relatedFicus species were specifically attracted to figs of their host species and only at the time when figs were ready to be pollinated. Some nonpollinating fig wasps appear to respond to the same volatile cues. PMID- 24242128 TI - Chemical signals involved in spacing behavior of breeding female bank voles (Clethrionomys glareolus Schreber 1780, Microtidae, Rodentia). AB - In order to study the mechanism involved in the seasonal territoriality of breeding bank voles, the social behavior and scent marking of paired females were observed throughout a reproductive cycle. Initially unfamiliar females were kept in large laboratory pens provided with individual burrows. After a brief period of hostility, females behaved in a friendly manner towards each other, sharing the same nest even in the presence of a male and until the middle of pregnancy. They scarcely marked with urine. Continuous olfactory assessment appeared to play an important role in maintaining the friendly interactions. In late pregnant and lactating females, on the contrary, the odor of a familiar female triggered aggressiveness and scent marking with urine and probably with flank glands. These reactions may be interpreted as spacing behavior. Moreover, the interaction between females may inhibit reproduction in one of them. These results are discussed in relation with the available ecological data. PMID- 24242129 TI - Evidence for sex pheromones produced by males and females inBlatta Orientalis (Dictyoptera, Blattidae). PMID- 24242130 TI - Nonfloral sources of chemicals that attract male euglossine bees (Apidae: Euglossini). PMID- 24242131 TI - Effects of Wenxiao Decoction on the expression of interleukin-6, intercellular adhesion molecular-1 and monocyte chemoattractant protein-1 in experimental atherosclerotic rabbits. AB - OBJECTIVE: To observe the effects of different doses of Wenxiao Decoction on the expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in experimental atherosclerotic rabbits and to explore the mechanism by which it alleviates atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into six groups: a blank group, a model group, a Simvastatin group, and high-, medium-, and low-dosage Wenxiao Decoction groups. Except for those in the blank group, all rabbits were fed with a high-cholesterol diet. Carotid atherosclerosis was established by balloon-induced carotid artery endothelium injury in conjunction with the high cholesterol diet. After 8 weeks, all animals were euthanized to evaluate levels of IL-6 and ICAM-1 expressions (by enzyme linked immunosorbent assay) and of MCP 1 (by immunohistochemistry staining). RESULTS: The expressions of IL-6, ICAM-1, and MCP-1 were significantly increased in all groups except the blank group (P<0.05). However, the rabbits in the Wenxiao Decoction groups and the Simvastatin group showed significantly lower levels of IL-6, ICAM-1, and MCP-1 expression than those in the model group (P<0.05). The expressions of IL-6, ICAM 1, and MCP-1 in the highdosage Wenxiao Decoction group and the Simvastatin group were lower than those in the low-dosage Wenxiao Decoction group (P<0.05). The expression of MCP-1 in medium-dosage Wenxiao Decoction group was lower than that in the low-dosage group (P<0.05). CONCLUSIONS: High, medium, and low doses of Wenxiao Decoction can inhibit the expressions of IL-6, ICAM-1, and MCP-1, which may prevent and stabilize atherosclerotic plaques. There may be a direct relationship between dosage and therapeutic efficacy of Wenxiao Decoction. PMID- 24242132 TI - Rubus parvifolius L. inhibited the growth of leukemia K562 cells in vitro and in vivo. AB - OBJECTIVE: To determine the antiproliferative activity of Rubus parvifolius L. (RP) extract, its medicinal serum and RP total saponins (RPTS) against K562 cells in vitro and in vivo. METHODS: Nude mice models bearing leukemia tumors were treated with different concentrations of RP extract. The size, weight and histopathological change of leukemic tumors were determined. Semi-solid agar culture and methylthiazolyl tetrazolium (MTT) assay were used to determine in vitro the inhibition of colony formation and proliferation of K562 cells respectively by different concentrations of RP medicinal serum and RPTS. RESULTS: RP extract had a tumor inhibition rate of 84.8% when administered to mice at a dose of 1.0 g/day of crude RP root equivalent. Semi-solid agar culture of K562 cells in the presence of 20% (v/v) of RP medicinal serum and 150 mg/L RPTS demonstrated a 50.8% and 100% inhibition of the colony forming unit (CFU)-K562, respectively. The same doses of RP medicinal serum and RPTS showed a proliferation inhibition of 31.4% and 86.3%, respectively against K562 cells in MTT assay. CONCLUSION: RP extract and RPTS show effective antiproliferative activity against myeloid leukemia cells in vitro and in vivo. PMID- 24242133 TI - Application of serum pharmacology in evaluating the antitumor effect of Fuzheng Yiliu Decoction from Chinese medicine. AB - OBJECTIVE: To investigate the feasibility of serum pharmacology in evaluating the antitumor effect of Chinese medicine (CM) of Fuzheng Guben (supporting the healthy energy and strengthening the body's resistance to pathogens), the effects of Fuzheng Yiliu Decoction (FYD), a typical prescription of Fuzheng Guben, on proliferation and apoptosis of hepatoma cells in vitro were observed by two methods with serum pharmacology and traditional pharmacology, respectively. METHODS: HepG2 cells were treated with FYD-containing serum or crude FYD extract in vitro. The proliferation rate was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis rate was performed by flow cytometry. And the levels of interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) in FYD-containing serum were detected by radioimmunoassay. RESULTS: FYD-containing serum remarkably inhibited proliferation and induced apoptosis of hepatoma cells at least by promoting the production of IL-2 and TNF-alpha in vivo. On the contrary, crude FYD extract promoted the proliferation and did not induce cell apoptosis. CONCLUSION: The results by serum pharmacology were accordant with those of our previous animal and clinical trials which indicates that serum pharmacology is a reasonable and feasible method for the evaluation of the antitumor effect of herbs of Fuzheng Guben. PMID- 24242134 TI - The effects of new herbal formula (KBMSI-2) on penile erection and expression of nitric oxide synthase isoforms in streptozotocin-induced diabetic rat model. AB - OBJECTIVE: To investigate the effects of new herbal formula (KBMSI-2) on erectile dysfunction in streptozotocin (STZ)-induced diabetic rat model. METHODS: Twenty four Sprague-Dawley male rats were randomly divided into three groups; control (n=8), diabetes model (n=8), diabetes + KBMSI-2 200 mg/kg treatment (n=8) groups. The diabetes induced groups received a single intraperitoneal injection of STZ. Distilled water was administered in the control and model groups. To investigate the penile erection, intracavernosal pressure (ICP) and intracavernosal pressure/mean arterial pressure (ICP/MAP) were recorded in all groups. Serial sections of the penis were used to perform Masson's trichrome stain. The expression of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and cyclic guanosine monophosphate (cGMP) concentration in the isolated corpus cavernosum were analyzed by Western blotting. RESULTS: Peak ICP/MAP ratio was increased in the KBMSI-2 treatment group compared with the model group (P<0.05). Masson's trichrome staining confirmed that the smooth muscle component was increased in the KBMSI-2 treatment group compared with the model group (P<0.05). The nNOS, eNOS and cGMP expression of KBMSI-2 200 mg/kg treatment group was increased compared with the model group (P<0.05). CONCLUSION: This study showed that herbal formula of KBMSI-2 improved the erectile function by preserving the smooth muscle content and inhibiting the fibrosis of the corpus cavernosum in STZ induced diabetic rat model. PMID- 24242135 TI - Hexane extract of the seeds of Byrsonima crassifolia accelerates wound healing in streptozotocin-induced diabetic rats. AB - OBJETIVE: To study the effect of seeds of Byrsonima crassifolia in diabetic wound healing. METHODS: Wound healing potential of hexane extract in the form of simple ointment for the treatment of dermal wounds was studied in streptozotocin-induced diabetic rats on excision wound, incision wound and dead space wound. Various parameters such as epithelization period, scar area, tensile strength, hydroxyproline, total protein, DNA, hexosamine, uronic acid, antioxidant enzymes including superoxide dismutase (SOD) and catalase activity (CAT) were used to evaluate the effect of B. crassifolia on wound healing. RESULTS: Hexane extract in form topical accelerates the wound healing process by decreasing the surface area of the wound with a significant increase in the rate of wound contraction and tensile strength; increase granulation tissue dry weight, hydroxyproline, total protein, DNA and SOD and CAT when compared with diabetic control. CONCLUSION: B. crassifolia was effective in promoting diabetic wound healing in rats through the processes of tissue regeneration. PMID- 24242136 TI - Effects of Fengbaisan on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung tissue of rats with chronic obstructive pulmonary disease. AB - OBJECTIVE: To observe effects of Fengbaisan (, FBS) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in lung tissue of rats with chronic obstructive pulmonary disease (COPD) and to investigate the preventive and therapeutic mechanisms of FBS. METHODS: The COPD rat model was established by cigarette smoke exposure and lipopolysaccharide (LPS) intra-tracheal dripping. The histopathological changes of lung tissue was observed via hematoxylin/eosin staining. The expression of MMP-9 and TIMP-1 in lung tissue was measured by reverse transcription polymerase chain reaction (RT PCR) and immunohistochemistry. RESULTS: The typical histopathological changes of COPD were displayed in the model group, Ambroxol Hydrochloride group and FBS group, and the pathological lesions in the FBS group were less than those in the model group. The expression of MMP-9 and TIMP-1 in the model group increased significantly compared with those in the normal group (P<0.05). After treatment for successive 28 days, the expression of MMP-9 and TIMP-1 in the FBS group decreased remarkably as compared with the model group (P<0.05). CONCLUSIONS: FBS can regulate MMP-9/TIMP-1 imbalance to prevent airway and lung parenchyma remodeling process via reducing the expression of MMP-9 and TIMP-1 in the lung tissue of COPD rats, and this may be a possible therapeutic mechanism of FBS on COPD. PMID- 24242137 TI - Effects of Trigonella foenum-graecum (L.) on retinal oxidative stress, and proinflammatory and angiogenic molecular biomarkers in streptozotocin-induced diabetic rats. AB - The aim of the present study was to investigate the protective effects of Trigonella foenum-graecum Linn. (fenugreek) in Streptozotocin-induced diabetic rat retina. Fenugreek (100 and 200 mg/kg body weights) treatment was carried out for 24 weeks and evaluated for inflammatory [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta] and angiogenic [vascular endothelial growth factor (VEGF) and protein kinase C (PKC)-beta] molecular biomarkers. Retinal oxidative stress was evaluated by estimating antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Fluorescein angiography was performed to detect retinal vascular leakage. Electron microscopy was performed to determine basement membrane thickness. In the present study, significant rises in the expressions of retinal inflammatory (TNF-alpha and IL-1beta) and angiogenic (VEGF and PKC-beta) molecular biomarkers were observed in diabetic retinae compared with normal retinae. However, fenugreek-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic molecular biomarkers. Moreover, results from the present study showed positive modulatory effects of fenugreek on retinal oxidative stress. Fluorescein angiograms and fundus photographs obtained from diabetic retinae showed retinal vascular leakage. On the other hand, fenugreek-treated retinae did not show vascular leakage. Further, thickened BM was recorded in diabetic retina compared with normal retinae. However, fenugreek treated retinae showed relatively lesser thickening of capillary BM. In conclusion, it may be postulated that fenugreek has great potential in preventing diabetes-induced retinal degeneration in humans after regular consumption in the specified dosage. PMID- 24242139 TI - [Addiction research in the Low Countries: alive and kicking!]. PMID- 24242138 TI - Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma. AB - Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR 141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1. PMID- 24242140 TI - The impact of Dutch and Flemish scientists on the progress of addiction medicine. PMID- 24242141 TI - [Impulse control in addiction: a translational perspective]. AB - BACKGROUND: Impulsivity is a hallmark of addiction and predicts treatment response and relapse. Impulsivity is, however, a complex construct. Translational cross-species research is needed to give us greater insight into the neurobiology and the role of impulsivity in addiction and to help with the development of new treatment strategies for improving patients' impulse control. AIM: To review recent evidence concerning the concept of impulsivity and the role of impulsivity in addiction. METHOD: The concept and neurobiology of impulsivity are reviewed from a translational perspective. The role of impulsivity in addiction and implications for treatment are discussed. RESULTS: Our recent translational cross species study indicates that impulsivity is made up of several, separate independent features with partly distinct underlying neurobiological substrates. There are also indications that these features make a unique and independent contribution to separate stages of the addiction cycle. CONCLUSION: In addition, the improvement of impulse control is a promising new target area for treatments that could lead to better results. However, those involved in developing new treatment strategies will have to take into account the complexity and multidimensional character of impulsivity. PMID- 24242142 TI - [Motivational processes in addiction: the role of craving, salience and attention]. AB - BACKGROUND: Motivational processes play an important role in addictive behaviours. Craving is mainly an explicit or conscious process that can motivate individuals to continue alcohol, take drugs or smoke cigarettes. Craving also plays a role in relapse; self-reported craving has often been associated with relapse. However, craving cannot explain all addictive behaviours. In addition to craving, implicit cognitive processes play an important part in motivating individuals to become involved in substance use. AIM: To describe some of these implicit cognitive processes, namely the role of salience, attention bias, automatic memory associations and action tendencies. METHOD: A description is given of recent research results and the implications of these implicit processes for clinical practice. RESULTS: Oversensitive/hypersensitive motivational processes and a lack of control over these processes both play an important role in addiction. This can be expressed by an uncontrollable urge to inject the drug or substance again, in spite of the fact that it is unwise for the person in question to do so. Recent research has shown that there are various very promising methods for dealing with these two problems (oversensitive/hypersensitive motivational processes and a lack of control over these processes), either separately or together. The methods involve behavioural training programmes, medication and neural stimulation. CONCLUSION: The research results are very promising, but more research is needed. PMID- 24242143 TI - [Neuromodulation as an intervention for addiction: overview and future prospects]. AB - BACKGROUND: In recent years several neuromodulation techniques have been introduced as interventions for addiction. AIM: To review and discuss studies that have investigated the effects of treating addiction by means of electroencephalography (EEG) neurofeedback, real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback, transcranial magnetic stimulation/transcranial direct current stimulation (TMS/tDCS) and deep brain stimulation (DBS). METHOD: We reviewed the literature, focusing on Dutch studies in particular. RESULTS: Studies using EEG neurofeedback were shown to have positive effects on drug use, treatment compliance, and cue reactivity in patients with cocaine and alcohol dependence. A pilot study investigating the effects of rt-fMRI neurofeedback on nicotine dependent patients showed that modulation of the anterior cingulate cortex can decrease smokers' craving for nicotine. In several studies decreased craving was found in alcohol dependent patients after TMS or tDCS stimulation of the anterior cingulate cortex or the dorsolateral prefrontal cortex. The first DBS pilot studies suggest that the nucleus accumbens is a promising target region for the treatment of alcohol and heroin dependence. CONCLUSION: Neuromodulation provides us with a unique opportunity to directly apply neuroscientific knowledge to the treatment of addiction. However, more research is needed to ensure the efficacy, safety and feasibility of the various neuromodulation techniques that are now available. PMID- 24242144 TI - [Dopamine and excessive alcohol consumption: how genes interact with their environment]. AB - BACKGROUND: Hereditary factors account for approximately 50% of the risk of developing alcohol dependence. Genes that affect the dopamine function in the brain have been extensively studied as candidate genes. AIM: To present the results of recent Dutch studies on the interaction between genes and their environment in relation to dopamine function and excessive alcohol use. METHOD: Two large scale research projects were recently carried out in order to study the relation between dopamine genes and excessive alcohol use in the Netherlands. The first study investigated excessive alcohol use among adolescents. The second studied alcohol dependence among adult males. RESULTS: Genes that affect the dopamine function in the brain were not directly linked to excessive alcohol use or dependence. Dopamine genes, however, do influence sensitivity to environmental risk factors for excessive alcohol use. CONCLUSION: These studies show that genetically determined dopamine function increases the risk of excessive alcohol use in the context of an adverse environment. Traumatic experiences and parenting style were both shown to be important environmental factors. PMID- 24242145 TI - [Substance use disorders and ADHD: an overview of recent Dutch research]. AB - BACKGROUND: ADHD is an important risk factor for the development of substance use disorders (SUD). AIM: To provide an overview of recent Dutch research into the prevalence of ADHD in SUD populations and the neurobiological substrate of the reduced effect of pharmacological treatment of this patient group. METHOD: We describe three studies: a meta-analysis and meta-regression analysis of the prevalence of ADHD in 6689 SUD patients; a cross-sectional study of the prevalence of ADHD and several other psychiatric disorders in 193 methadon maintenance patients, and finally a study in which the availability and occupation of dopamine transporters before and after methylphenidate treatment were measured using SPECT scans in 24 ADHD patients with and without cocaine addiction. RESULTS: The prevalence of ADHD in SUD patients is estimated to be 23.1% (95% confidence interval 19.4-27.2). This prevalence is influenced by the diagnostic instrument for ADHD and by the substance of abuse: cocaine is associated with a lower ADHD prevalence than other substances. The prevalence found among methadone maintenance patients was similar, namely 24.9%; additional comorbid psychiatric disorders were also frequently present. In the imaging study, lower availability of dopamine transporters and lower occupation by methylphenidate were found in cocaine-dependent ADHD patients than in ADHD patients without SUD. CONCLUSION: These studies confirm the high prevalence of ADHD in SUD patients, and provide a possible explanation for the reduced efficacy of methylphenidate in this patient population. PMID- 24242146 TI - [Cannabis use and the risk of psychotic disorders. An update]. AB - BACKGROUND: The use of cannabis has been linked to an increased risk for psychosis, irrespective of confounding factors such as age, gender, use of other drugs and reverse causality. Over the last few years a great deal of research has been done to broaden our understanding of the underlying mechanisms of this link. AIM: To update studies that have examined the link between cannabis use and psychosis and that have investigated the possible mechanisms underlying this link. METHOD: This article discusses recent epidemiological and experimental research that sheds light on the nature of the link and the influence of interactions between genes and environment. RESULTS: The long-term effects of cannabis on the risk factors for psychosis and psychotic disorders are influenced to a large extent by genetic and environmental factors. Furthermore, patients with a psychotic disorder seem to be extremely vulnerable to the acute effects of cannabis. CONCLUSION: Studies show that cannabis use is an important risk factor for psychosis and psychotic disorders. So far, however, less research has been done into the effects of cannabis use on patients already suffering from a psychotic disorder. PMID- 24242149 TI - [Detoxification of patients with GHB dependence]. AB - BACKGROUND: A new detoxification method for GHB dependence was developed recently in the Netherlands. The method involves the use of pharmaceutical GHB. AIM: To describe the characteristics of GHB dependent inpatients, the course of the detoxification process and patients' progress in the three months following inpatient detoxification. METHOD: 229 GHB dependent patients were monitored during and after inpatient detoxification. Records were kept of the psychiatric symptoms, withdrawal symptoms and relapses. RESULTS: The average age of the patients was 29 years; 69% of the patients were male. They reported severe symptoms of co-occurring depression and anxiety. Detoxification was successful in 86% of the patients and, on a whole, the procedure ran smoothly, without complications. However, within three months following detoxification two-thirds of the patients had relapsed and were again taking GHB. CONCLUSION: Pharmaceutical GHB can be used as an alternative to the benzodiazepine method for detoxifying patients with GHB dependence. However, the high relapse rates following detoxification are of great concern. PMID- 24242150 TI - [Pharmacogenetics in the treatment of tobacco addiction]. AB - BACKGROUND: Smokers vary in their genetic susceptibility to become addicted to smoking and probably also in their reaction to smoking cessation pharmacotherapies. AIM: To provide an overview of the developments on the pharmacogenetics of the treatment of tobacco addiction. METHOD: Review article describing the biological processes associated with tobacco addiction, and the influence of genetic variants on smoking behavior and the efficacy of smoking cessation therapies. RESULTS: Several (combinations of) genetic variants in smoking-related genes influence nicotine dependence. Moreover, several genetic variants in smoking- and treatment-related genes seem to influence the efficacy of smoking cessation therapies which are distinctive for the different forms of pharmacotherapy, especially when they have a different mechanism-of-action. CONCLUSION: Much progress has been made in unraveling the (pharmaco)genetics of tobacco addiction, but much still remains to be done before genetically tailored smoking cessation therapy can be implemented in clinical practice. PMID- 24242151 TI - [Developments in pharmacotherapy: personalised pharmacotherapy?]. AB - BACKGROUND: Effect-sizes of pharmacological treatments for addictive disorders are limited and a substantial number of patients do not derive any benefit from these treatments. AIM: To develop strategies that will enhance the effectivity of pharmacotherapy in the future. METHOD: We reviewed the literature using a model of staging and profiling which matches pharmacological interventions to specific stages of addiction. RESULTS: Pharmacological interventions can be tailored to the specific stage of the disease. In the early stages of a disease, pharmacotherapy can be directed towards reducing impulsivity, craving and compulsive behaviour and controlling substance abuse. In later stages the aim is to reduce negative effects, craving and compulsive behaviour and bring the patient to the stage of total abstinence. Furthermore, if therapists opt for pharmacotherapy they must take specific characteristics of the patient into consideration. Currently, phenotypical (clinical) characteristics do not provide a firm enough basis for pharmacological interventions. Endophenotypical or genetic characteristics seem to be very promising. However, most findings still need to be replicated and validated. CONCLUSION: The era of truly personalised medication for addiction has not yet arrived, but there are some very promising developments. In the short term, the prospects for pharmacogenetics seem to be the most favourable. A model of staging and profiling can provide a valuable framework for new developments in pharmacotherapy. PMID- 24242152 TI - [Psychological treatment in substance use disorders: focus for the future]. AB - BACKGROUND: Cognitive behavioural therapy and motivational interviewing are evidence-based treatments for substance use disorders (SUDs). However, treatment for SUDs is still at an early stage and patients are being deprived of many new forms of treatment from which they could benefit. Low treatment compliance and limited treatment success are also problems that need attention. AIM: To find out from the literature how these problems can be or are being tackled and to formulate suggestions for improvements. METHOD: We reviewed the literature, collecting and formulating suggestions about possible improvements in the treatment of SUD patients. We mention strategies to reduce the treatment gap, to improve treatment compliance and treatment results. RESULTS: According to the literature, clinics and hospital wards can introduce more structured screening for substance use disorders. Internet treatment has proven to lower the threshold for treatment. Patients reluctant to begin treatment can be motivated by their loved ones (via CRAFT) to join treatment programmes. E-health is a promising technique for enhancing patients' compliance with tasks that can be performed at home. The addition of contingency management can increase treatment compliance and encourage abstinence. Furthermore, the treatment of comorbid psychiatric disorders and the provision of continuing-care are strategies that are likely to optimise treatment results. CONCLUSION: A number of viable strategies are available or are being developed for improving the treatment of SUD patients. Dutch research has made an important contribution in this area. PMID- 24242153 TI - Perceived discrimination and religiosity as potential mediating factors between migration and depressive symptoms: a transnational study of an indigenous Mayan population. AB - Evidence suggests that in the US perceived discrimination among migrants of Mexican origin is associated with depressive symptoms. Factors that confer resilience, such as religiosity, could serve as a mediating factor in the context of migration stressors. We hypothesized that migration is associated with higher depressive symptoms and that discrimination and religiosity would mediate this relationship in a binational (US and Mexican) sample of indigenous Mexican migrants. We applied path analysis modeling to test our hypotheses with a sample of 650 individuals (n = 583 in Mexico; n = 67 in US). Results indicated that migration experience and current US residence were associated with perceived discrimination, which in turn were associated with a higher risk for depressive symptoms. Among women not living in the US, religiosity was associated with lower perceived discrimination. Discrimination is pervasive among male and female transnational and domestic migrants and religiosity may serve as a protective factor against discrimination for some women. PMID- 24242154 TI - A muslim family with several members with celiac disease and other autoimmune disorders. AB - The Bedouin community of Israel is a traditional Muslim society. It is characterized by one of the highest rates of population growth in the world. The custom of intermarriage, especially among cousins or within the extended family, is very common because of the community's tribal structure. The rate of genetic disease in this population is high. We present a Bedouin family in which the father suffers from celiac disease and Hashimoto's disease, his daughter has celiac and Crohn's disease, three other children have IgA deficiency, and a half uncle has Crohn's disease. In describing this family we present the familial nature of these diseases, the age at diagnosis, the marital relationships of the family members and co-morbid diseases and medical conditions. Family doctors can develop and use genograms that can facilitate their understanding of the situation and enable them to develop plans for health promotion and disease prevention counseling in the community. PMID- 24242156 TI - Presymptomatic testing for huntington diseases: Recommendations for counseling. AB - The discovery of a genetic marker linked to the Huntington disease (HD) gene made it possible to perform presymptomatic genetic testing for this late onset disorder. The first two pilot research programs in the United States, at Massachusetts General Hospital and Johns Hopkins Hospital, began offering testing in the Fall of 1986. Twenty-three centers are now offering this testing as part of their clinical service. As testing for this and other late onset diseases becomes more widespread, it is important to assess what we have learned about offering this test to those at risk. This article presents recommendations based on the author's 5 years of experience offering presymptomatic testing for HD in order to alert counselors to the complexities of offering this type of service. PMID- 24242155 TI - Meeting physical activity guidelines is associated with lower allostatic load and inflammation in Mexican Americans. AB - Examine the relationship between physical activity (PA) and allostatic load in Mexican-Americans as well as variations by gender. Self-reported PA as well as cardiovascular, metabolic and inflammatory markers were assessed in 330 Mexican American adults in the Cameron County Hispanic Cohort (Brownsville, TX, USA). Dependent variables included total allostatic load, blood pressure, metabolic, and inflammatory scores. PA participation was categorized as sedentary, low, moderate, high, and by whether activity was sufficient to meet public health guidelines. Logistic regression analyses were conducted using cross-sectional data, and tested interaction effects of gender and PA. High active participants had lower allostatic load and inflammatory risk than sedentary participants. These relationships held for meeting versus not meeting guidelines. Males meeting guidelines were less likely to have high inflammation than other groups. The data did not suggest a dose-response association. These findings indicate that PA may reduce accumulation of allostatic load, highlighting the importance of a physically active lifestyle across the life span. PMID- 24242157 TI - Psychological aspects of genetic counseling. VIII. Suffering and countertransference. AB - Two common forms of countertransferential problems seen in genetic counseling, associative and projective, are described and illustrated. Both forms have the potential of reducing the quality of empathy counselors provide counselees. When counselors experience the same problems as the counselees they counsel it is virtually impossible to avoid facing countertransferential reactions which may not always promote the counselees' interests and/or redound to their benefit. Genetic counselors, like other personal counselors and psychotherapists, have a professional responsibility to be aware of, monitor, contain, and learn from their countertransferential experiences. PMID- 24242158 TI - Abstracts of papers presented at the eleventh annual education conference. PMID- 24242159 TI - The impact of ultrasound. PMID- 24242160 TI - Silencing of an aphid carboxylesterase gene by use of plant-mediated RNAi impairs Sitobion avenae tolerance of Phoxim insecticides. AB - RNA interference (RNAi) describes the ability of double-stranded RNA (dsRNA) to inhibit homologous gene expression at the RNA level. Its specificity is sequence based and depends on the sequence of one strand of the dsRNA corresponding to part or all of a specific gene transcript. In this study we adopted plant mediated RNAi technology that targets Sitobion avenae (S. avenae) to enable gene silencing in the aphid and to minimize handling of the insects during experiments. S. avenae was selected for this study because it causes serious economic losses to wheat throughout the world. The carboxylesterase (CbE E4) gene in S. avenae was homologously cloned, which increased synthesis of a protein known to be critical to the resistance (tolerance) this species has developed to a wide range of pesticides. A plant RNAi vector was constructed, and transgenic Triticum aestivum (dsCbE1-5 and dsCbE2-2 lines) expressing CbE E4 dsRNA were developed. S. avenae were fed on dsCbE1-5 and dsCbE2-2 lines stably producing the CbE E4 dsRNA. CbE E4 gene expression in S. avenae was reduced by up to 30-60%. The number of aphids raised on dsCbE1-5 and dsCbE2-2 was lower than the number raised on non-transgenic plants. A solution of CbE E4 enzyme from S. avenae fed on dsCbE1-5 and dsCbE2-2 plants hydrolyzed only up to 20-30% Phoxim solution within 40 min whereas a solution of the enzyme from CbE E4 fed on control plants hydrolyzed 60% of Phoxim solution within 40 min. CbE E4 gene silencing was achieved by our wheat-mediated RNAi approach. This plant-mediated RNAi approach for addressing degradation-based pesticide resistance mechanisms in aphids and may prove useful in pest management for diverse agro-ecosystems. PMID- 24242161 TI - Enhanced enteric virus detection in sporadic gastroenteritis using a multi-target real-time PCR panel: a one-year study. AB - Viral gastroenteritis causes significant mortality and morbidity worldwide. Identifying the etiology of viral gastroenteritis is a challenge as most enteric viruses (EVs) are non-culturable. This study is to develop an EV testing panel using real-time PCR (EVPrtPCR) to simultaneously detect rotavirus, norovirus, sapovirus, astrovirus, and enteric adenovirus in stool samples. EVPrtPCR using universal amplification conditions was run in a single instrument run. EVPrtPCR was used to test 2,486 sporadic gastroenteritis samples submitted for EV testing using electron microscopy (EM) between July 2008 and July 2009. Retesting spiked negative stool samples and Salmon DNA as internal control were used to evaluate inhibition. EVPrtPCR detected viruses in significantly more samples: 748 (34%) as compared to 94 (3.8%) by EM. EM did not detect any norovirus, sapovirus, and mixed infection, and detected only 39% of rotavirus and 38.2% of enteric adenovirus positive samples. Four samples that tested positive for rotavirus and two for adenovirus and for small-round-structured viruses by EM were negative by EVPrtPCR. Norovirus was the most common virus detected (17.6%) with 92.4% as genogroup II, followed by rotavirus (6.8%), sapovirus (4.2%), astrovirus (2.0%), and enteric adenovirus (1.4%) with 9% samples positive for mixed infection. Overall, EV identification followed a U-shaped age distribution; positive samples were more common in children <=5 years old and adults >60 years old. Norovirus, sapovirus and astrovirus showed winter predominance and rotavirus peaked in the spring. No inhibition was observed. Molecular technology significantly enhanced the identification of EV causing sporadic gastroenteritis in Alberta. PMID- 24242162 TI - High solids enzymatic hydrolysis of pretreated lignocellulosic materials with a powerful stirrer concept. AB - In this study, we present a powerful stirred tank reactor system that can efficiently hydrolyse lignocellulosic material at high solid content to produce hydrolysates with glucose concentration > 100 g/kg. As lignocellulosic substrates alkaline-pretreated wheat straw and organosolv-pretreated beech wood were used. The developed vertical reactor was equipped with a segmented helical stirrer, which was specially designed for high biomass hydrolysis. The stirrer was characterised according to mixing behaviour and power input. To minimise the cellulase dosage, a response surface plan was used. With the empirical relationship between glucose yield, cellulase loading and solid content, the minimal cellulase dosage was calculated to reach at least 70% yield at high glucose and high substrate concentrations within 48 h. The optimisation resulted in a minimal enzyme dosage of 30 FPU/g dry matter (DM) for the hydrolysis of wheat straw and 20 FPU/g DM for the hydrolysis of beech wood. By transferring the hydrolysis reaction from shaking flasks to the stirred tank reactor, the glucose yields could be increased. Using the developed stirred tank reactor system, alkaline-pretreated wheat straw could be converted to 110 g/kg glucose (76%) at a solid content of 20% (w/w) after 48 h. Organosolv-pretreated beech wood could be efficiently hydrolysed even at 30% (w/w) DM, giving 150 g/kg glucose (72%). PMID- 24242163 TI - Atmospheric pressure plasma pretreatment of sugarcane bagasse: the influence of biomass particle size in the ozonation process. AB - Atmospheric pressure O2 plasma was used to produce ozone in order to treat sugarcane bagasse as a function of particle sizes. The fixed bagasse moisture content was 50%. The delignification efficiency had small improvement due to ozonation process as a function of particle size, varying from 75 up to 80%. Few amounts of hemicellulose were removed, but the ozonation has not been affected significantly with particle size variance as well (from 30 up to 35%). The cellulose presented some losses below 1.0 mm size (8-15%) which was an unexpected result. The conversion of cellulose content into free sugar has shown a significant increase as the particle size has diminished as well. The best condition of the bagasse particle size was for 0.08 mm. For this case, a great quantity of cellulose (78.8%) was converted into glucose. Optical absorption spectroscopy was applied to determine ozone concentrations in real time where the samples with typical bagasse particle sizes equal or below to 0.5 mm had shown a better absorption of ozone in comparison with greater particle size samples. PMID- 24242164 TI - 1,2-diazole and 2,2,2-trifluoroethanol and their regulatory effects on ethanol and lactic acid formation in the living culture of Rhizopus oryzae. AB - In heterofermentation of Rhizopus oryzae, ethanol is the major byproduct which reduces the production of a desired product, an optically pure L-lactic acid. To improve lactic acid production, regulating the alcohol fermentative pathway to limit ethanol production has been done by various techniques. In vitro study on alcohol dehydrogenase (ADH) inhibition in several organisms showed that 1,2 diazole and 2,2,2-trifluoroethanol were competitively bound at the active sites that eventually limited ethanol production. In this study, 1,2-diazole and 2,2,2 trifluoroethanol were present during fermentation of R. oryzae. It was found that both 1,2-diazole and 2,2,2-trifluoroethanol not only strongly affected ethanol formation but they also indirectly regulated lactate production as observed by the decreasing affinity for glucose flux toward lactate and ethanol production. The increase in both ethanol and lactate formation rates revealed 1,2-diazole and 2,2,2-trifluoroethanol not only regulated the reversible redox reaction by ADH, but they also caused the dynamic change in the conversion of all metabolites in the living R. oryzae in order to maintain the balanced flux for cellular growth and maintenance. PMID- 24242165 TI - alpha-Glucosidase inhibition and antioxidant properties of Streptomyces sp.: in vitro. AB - Streptomyces strain isolated from the soil sediment was studied for its in vitro alpha-glucosidase and antioxidant properties. Morphological characterization and 16S rRNA partial gene sequencing were carried out to confirm that the strain Loyola AR1 belongs to genus Streptomyces sp. Modified nutrient glucose broth was used as the basal medium for growth and metabolites production. Ethyl acetate extract of Loyola AR1 (EA-Loyola AR1) showed 50% alpha-glucosidase inhibition at the concentration of 860.50 +/- 2.68 MUg/ml. Antioxidant properties such as total phenolic content of EA-Loyola AR1 was 176.83 +/- 1.17 mg of catechol equivalents/g extracts. EA-Loyola AR1 showed significant scavenging activity on 2,2-diphenyl-picrylhydrazyl (50% inhibition (IC50), 750.50 +/- 1.61 MUg/ml), hydroxyl (IC50, 690.20 +/- 2.38 MUg/ml), nitric oxide (IC50, 850.50 +/- 1.77 MUg/ml), and superoxide (IC50, 880.08 +/- 1.80 MUg/ml) radicals, as well as reducing power. EA-Loyola AR1 showed strong suppressive effect on lipid peroxidation (IC50, 670.50 +/- 2.52 MUg/ml). Antioxidants of beta-carotene linoleate model system reveals significantly lower than butylated hydroxyanisole. PMID- 24242166 TI - Immunohistochemical and Western blot analysis of two protein tyrosine phosphatase receptors, R and Z1, in colorectal carcinoma, colon adenoma and normal colon tissues. AB - Two classes of proteins, namely tyrosine kinases (PTK) and phosphatases (PTP), play an important role in cell proliferation and differentiation, thus leading to an acceleration or inhibition of tumour growth. The role of the above proteins in colorectal carcinoma (CRC) growth is a well-known event. In this study we carried out immunohistochemical and Western blot analysis of colorectal carcinoma, adenoma and normal colon tissue in relation to two protein tyrosine phosphatase receptors, R and Z1. Twenty-five cases of CRC were analyzed and the results were compared with similar data obtained in non-malignant tissues. High expression of both PTP receptors was observed in all examined cases of CRC, adenoma and normal colon tissue in this study. These results are not in line with recently published data, showing that genetic coding for PTPRR and PTPRZ1 were hypermethylated in CRC's. We presume that the protein tyrosine phosphatase overexpression in colorectal carcinoma is not enough to protect from the progression of disease. PMID- 24242167 TI - Photodissociation spectroscopy of gas-phase ferrocene cation. AB - The optical absorption spectrum of gas-phase ferrocene cation was measured by photodissociation (PO) spectroscopy between 570 nm and 643 nm. The PO process was loss of a cyclopentadienyl ring from the parent cation. Some structure was observed in the PO spectrum, with the highest PO being at 603 nm. The peak spacing did not correspond to a vibrational progression in the expected totally symmetric vibrational mode, and a possible assignment of the three apparent maxima involving electronic transitions from low-lying electronic states is proposed. Information on the dissociation threshold was sought by light intensity dependence measurements at 308 nm, 266 nm, and time-resolved PD measurements at 308 nrn, 266 nrn, and 240 nm. The PD at all of these wavelengths showed two photon characteristics, indicating that the threshold for observable one-photon PO lies higher than about 5.4 eV. PMID- 24242168 TI - Ion decomposition versus molecular size probed by vacuum ultraviolet photoionization. AB - The molecular size dependence of primary fragmentation is studied for a series of beta -naphthyl esters having alkyl chain lengths from C2 to C18. The esters are vaporized at a known ftemperature and ionized by coherent vacuum ultraviolet radiation at 10.5 eV. The photoionization wavelength is energetic enough to cause both metastable and nonmetastable primary fragmentation to m / z 144, but not energetic enough to cause secondary fragmentation to m / z 115 or 116. Under these conditions, the ratio of the nonmetastable-to-metastable daughter ion current, D/m D (') is expected to give a rough indication of the average parent ion dissociation rate. The D / m D ratio decreases with increasing molecular size, but not as quickly as expected by simple RRK theory. This behavior along with temperature dependence studies suggests that the internal energy required for dissociation is provided in substantial part by both the initial thermal internal energy and the energy imparted by the photoionization step. The role of thermal energy in the dissociation of large ions is discussed. PMID- 24242169 TI - Double-ionization energies to ground and excited states of the tungsten hexacarbonyl dication. AB - Tungsten hexacarbonyl was investigated by double-charge-transfer (DCT) spectroscoPy, and the double-ionization energies to ground and electronically excited states of W(CO) 6 (2+) determined. The double-ionization energies corresponding to the first two distinct peaks in the spectra are 22.8 +/- 0.3 eV and 28.5 +/- 0.3 eV, but numerous overlapping peaks at higher energies are evident. It is shown that the DeI spectra can explain the main features of a previously determined (J. Am. Soc. Mass Spectrom. 1990, 1, 16-27) internal energy distribution curve for W(CO) 6 (2+) ions formed by 70-eV electron ionization of W(CO)6 molecules. PMID- 24242170 TI - Tandem mass spectrometry studies of acetone and acetone/water cluster ions. AB - Ion clusters were formed in a temperature-variable high-pressure ion source from neat acetone and acetone/water mixtures and subjected to tandem mass spectrometry studies-unimolecular and collisionally activated mass-analyzed ion kinetic energy spectroscopy. The predominance of water loss from H(+)(H20)(A) l=3, where A = acetone, suggests that the solvation sphere around H3O(+) does not close at l = 3, contrary to the case of acetonitrile or dimethyl ether. The results may be interpreted in terms of suggested ion structures which involve isomerization enroute to dissociation. The virtual absence of H/D scrambling in the collisionally activated dissociation of H3O(+)(DA)3, DA =acetone-d 6, and of D3O(+)(A)3 means that if enolization takes place, it is a rate-determining step in an irreversible isomerization. The stability of H(+)(H2O)(A)3 is a dominant factor in the observation of acetone loss from H(+)(H20)(A)4. PMID- 24242171 TI - Ion-molecule reaction of alkanenitriles and transition-metal ions in the gas phase: A study on fragmentation mechanism of the adducts. AB - Gas-phase ion-molecule reactions between transition-metal ions (Mn +, Fe+, Co+, Ni +) and propionitri1e and acetonitrile were investigated. Ion-molecule adducts were prepared in a modified fast atom bombardment source and their metastable and collision-induced fragmentations, occurring in the frrst held-free region of an E/B configuration instrument, were studied by means of B/E linked scans. The experimental data suggest a coexistence of both "end-on" and "side-on" coordination modes; the former undergoes ligand detachment alone, whereas the latter loses methyl and ethyl radicals by insertion of M+ into organic substrates and further produces ethylene via a l3-hydrogen transfer. An order for the bonding energy of RCN-M+ is also suggested: RCN-Ni+> RCN-Co+> RCN-Fe+> RCNMn+. PMID- 24242172 TI - Effects of N-substitution on the fragmentations of some cyclohexene-fused 2-N phenyliminoperhydro-3,1-oxazines and related thiazines. AB - Six cyclohexene-fused 2-N-phenyliminoperhydro-3,1-oxazines and four related thiazines were prepared and their mass spectrometric behavior was studied by means of metastable ion analysis and exact mass measurement. In most of the fragmentations, extensive rearrangements took place. The decompositions through the retro-Diels-Alder reaction initiated by the double bond dominated in the case of the unsubstituted compounds. The effect of the double bond, however, was greatly outweighed by the effect of the substituent on the ring nitrogen atom. In comparison with the unsubstituted compounds, both electron-releasing (methyl) and electron-withdrawing (benzyl) substituents increased the contribution of the ring cleavage reactions in the heterocyclic part of the molecule; in the case of the benzyl group the loss of the substituent also became important. For isomeric compounds, the relative peak intensities were so different that such compounds were easy to differentiate. PMID- 24242173 TI - Structural studies on alkylisocyanate polymers by thermal degradation tandem mass spectrometry. AB - Homopolymers and copolymers of alkylisocyanates having n-hexyl, 2,6 dimethylheptyl, 3,7-dimethyloctyl, and (2,2-dimethyl-1,3-dioxolan-4-yl)methyl substituents underwent thermal degradation in the course of desorption electron ionization to yield trimers and monomers that were characterized in situ by tandem mass spectrometry. The trimers were trisubstituted cyanuric acids, the protonated molecules displaying a characteristic series of alkene eliminations on collision-induced dissociation to yield protonated cyanuric acid, m/ z 130. Confirmation of the identity of the pyrolysates was obtained by using two types of MS3 experiments: the reaction intermediate scan and the two-dimensional familial scan. The ion chemistry of the trimers and of the protonated monomer, the alkylisocyanate, was elucidated. Among the many interesting fragmentation processes undergone by the ionized trimers were a and 3 C-C bond cleavages and charge-remote fragmentations, which provided information on branching in the alkyl substituent. The dioxolane-containing substituent showed unique ion chemistry. The monomer distribution in the copolymers was deduced from the abundances of the various protonated trimers. The distribution was found to be random in all copolymers except that containing the dioxolane substituent. PMID- 24242174 TI - Electrospray mass spectrometry for the analysis of opioid peptides and for the quantification of endogenous methionine enkephalin and beta-endorphin. AB - Electrospray ionization mass spectrometry was used to characterize several different neuropeptides, whose molecular weights ranged from 555 to 3463 Da, and to quantify endogenous methionine enkephalin (ME) and beta -endorphin (beta E) extracted from a human pituitary gland. Methionine enkephalin and leucine enkephalin both yield only an [M + H] + ion with electrospray mass spectrometry; the other peptides produce a series of multiply charged even-electron molecular ions of the general nature [M + nH](n)+ in proportion to the number of basic amino acid units present, with no evidence of fragmentation. The electrospray mass spectra are characterized by low background noise. The quantiftcation of ME is based on a comliarison of the ion current due to the [M + H] + ion of native and of a deuterated ME ([(2)H5 s-(4)Phe]-ME) internal standard. The calibration curve is linear in the range of ca. 1-35 pmol synthetic ME. The amounts of ME determined in three separate human pituitary extracts were 9.1, 8.2, and 4.7 pmol/mg protein. The corresponding amount of ME in a canine pituitary was 39.8 pmol/mg protein. To quantify beta E, the ion current due to the [M + 5H](5) + ion was monitored and compared to an external calibration curve obtained by analyzing solutions of synthetic beta E in the range 5 MUmol-50 pmol. The analysis of a human pituitary yielded 660 fmol beta E/mg protein. PMID- 24242175 TI - Continuous-flow fast atom bombardment mass spectrometry of oligonucleotides. AB - Although frit-fast atom bombardment (frit-FAB) and continuous-flow FAB mass spectrometry have become standard methods for the analysis of peptides and peptide mixtures, these techniques have not been applied previously to the analysis of oligonucleotides. Mobilephase composition, flow rate, and sample size were optimized for the analysis of oligonucleotides by negative ion frit-FAB mass spectrometry (a type of continuous-flow FAB mass spectrometry). With a mobile phase consisting of methanol/water/triethanolamine (80:20:0.5, v/v/w), flow injection frit-FAB analysis of oligonucleotides showed lower limits of detection compared to standard probe FAB mass spectrometry. For example, in order to obtain a signal-to-noise ratio of 3:1, 38 prnol of d(GTIAAC) were required for frit-FAB mass spectrometry and 62 pmol were required for standard probe FAB mass spectrometry. The largest difference between frit-FAB and standard probe FAB was observed for d(pC)5, for which the limit of detection by frit-FAB was approximately 11-fold lower than by standard FAB mass spectrometry. Adjustment of the mobile phase to pH 7 with trifluoroacetic acid increased the limit of detection (reduced sensitivity) a minimum of sixfold. Equimolar mixtures of two or three oligonucleotides produced deprotonated molecules in identical relative abundances whether analyzed by frit-FAB or standard probe FAB mass spectrometry. Finally, frit-FAB liquid chromatography mass spectrometry was demonstrated by separating mixtures of oligonucleotides on a beta -cyclodextrin high-performance liquid chromatography column with a mobile phase containing methanol, water, and triethanolamine. PMID- 24242176 TI - Quantitative analysis by high-performance liquid chromatography atmospheric pressure chemical ionization mass spectrometry: The determination of the renin inhibitor CP-80,794 in human serum. AB - A specific method was developed for the quantitative determination of the renin inhibitor CP-BO,794. Serum extracts containing the drug and an internal standard were injected into a standard reverse-phase high-performance liquid chromatography (HPLC) column. The mobile phase, methanol/water (8/2), flowed at 1 ml/min through the column and then via a heated nebulizer interface into a corona discharge atmospheric pressure chemical ionization source. The assay minimum limit of quantification was 50 pg/mL. It exhibits satisfactory accuracy and precision over the range 50 pg/ml, to 10 ng/mL. A minor modification of the HPLC mobile phase was necessary to attain extremely low detection limits. The addition of a structural analogue contributed to enhancing the precision of the assay. PMID- 24242177 TI - An automatic reaction control chemical ionization technique in ion trap detector for quantitative plasma profding of arecoline in treated alzheimer patients. AB - An automatic reaction control chemical ionization technique in an ion trap detector (lTD) was used to quantitate the levels of the cholinergic drug, arecoline, in plasma of treated patients with Alzheimer's disease. The chemical ionization reaction was carried out with acetonitrile. The protonated molecules of arecoline (m I z 156) and the internal standard, homoarecoline (m / z 170), were monitored. Human plasma samples were extracted with a readily evaporable solvent mixture, the residues reconstituted and injected along with a tertiary amine-carrier into a capillary gas chromatograph interfaced with the ITD. Standard curves for plasma-extracted arecoline between 20-ng/mL and 156-pg/mL levels were linear (r> 0.9980). Satisfactory precision (relative standard deviation < 20%) and accuracy (relative error < 15%) at the limit of quantitation, 156 pg/mL arecoline, were achieved. Optimal conditions for handling of blood samples obtained by venipuncture were determined. The assay was successfully applied for the therapeutic monitoring of Alzheimer patients treated intravenously with arecoline. PMID- 24242178 TI - A computer program (COMPOST) for predicting mass spectrometric information from known amino acid sequences. AB - A computer program (COMPOST) is described that carries out predictive computations on known amino acid sequences. The program is designed to be of use to mass spectrometrists with an interest in protein and peptide sequencing. Mass values (monoisotopic and average) for protonated peptide and protein molecules and elemental compositions are calculated. COMPOST also calculates mass to charge ratio values for protonated peptides expected from specified digests, locates specified amino acid subsequences or peptides of a specifIed molecular weight within a longer sequence, and predicts mass to charge ratio values for fragment ions from high-energy collision-induced dissociation of protonated peptides. PMID- 24242179 TI - Ion-neutral complexes in gas-phase dissociations of protonated nitriles: n-C3H 7CNH (+) and i-C 3H 7CNH (+). PMID- 24242180 TI - A charge-remote allylic cleavage reaction: Mechanistic possibilities. AB - The collision-induced allylic cleavage reactions of deuterium-labeled [M - H + 2Li)(+) and [M - H](-) ions of monounsaturated fatty acids were investigated. Three concerted mechanistic possibilities were considered for this process: a l,4 elimination of a vinylic H, a retro-ene reaction, and a l,4-conjugate elimination. A fourth mechanistic possibility, a two-step radical version of the retro-ene and l,4-conjugate elimination reactions, was also considered. The radical reactions are in accord with the isotopic labeling results and offer certain mechanistic consistencies for cleavage of both C-C allyl bonds; they are expected, however, to have large activation energies. The lower-energy concerted alternatives, the retro-ene reaction for cleavage of the proximal and the l,4 conjugate elimination for cleavage of the distal C-C allyl bond, are also consistent with experimental results. The alternative of two different concerted mechanisms for cleavage of the two allyl bonds, however, is at odds with the charge-remote concept. PMID- 24242182 TI - Passages 2014. PMID- 24242183 TI - Sex- and age-interacting eQTLs in human complex diseases. AB - Many complex human diseases exhibit sex or age differences in gene expression. However, the presence and the extent of genotype-specific variations in gene regulation are largely unknown. Here, we report results of a comprehensive analysis of expression regulation of genetic variation related to 11,672 complex disease-associated SNPs as a function of sex and age in whole-blood-derived RNA from 5254 individuals. At false discovery rate <0.05, we identified 14 sex- and 10 age-interacting expression quantitative trait loci (eQTLs). We show that these eQTLs are also associated with many sex- or age-associated traits. These findings provide important context regarding the regulation of phenotypes by genotype environment interaction. PMID- 24242185 TI - Influence of axial length on ganglion cell complex (GCC) thickness and on GCC thickness to retinal thickness ratios in young adults. AB - PURPOSE: The present study was designed to investigate the influence of axial length on macular ganglion cell complex (GCC) thickness and two ratio parameters the GCC thickness to macular total retinal thickness (G/T) ratio and the GCC thickness to macular outer retinal thickness (G/O) ratio-using spectral-domain optical coherence tomography (OCT). METHODS: In this prospective case series, 74 eyes of 74 healthy Japanese study participants with varying degrees of myopia were recruited. GCC, outer retinal, and total retinal thicknesses were measured with the RTVue-100 system. The G/T and G/O ratios were also calculated. The axial length was determined using the IOLMaster. The correlation between the OCT measurements and axial length was evaluated. RESULTS: The average axial length was 25.05 +/- 1.38 mm. The GCC thickness was significantly correlated with axial length (r = -0.384, P = 0.001). The outer retinal thickness and the total retinal thickness were significantly correlated with axial length (r = -0.444, P < 0.001 and r = -0.493, P < 0.001, respectively), but the G/T and G/O ratios were not (r = -0.093, P = 0.428 and r = -0.091, P = 0.440, respectively). CONCLUSIONS: GCC thickness is affected by axial length. Because the prevalence of myopia is high in Japan, when determining the GCC thickness of Japanese individuals, it seems necessary to consider the axial length as well. To take account of individual variation in axial length, we propose the ratio parameters as a suitable parameter. PMID- 24242186 TI - Letter to Dr. Khuri. PMID- 24242187 TI - Prolyl hydroxylase inhibitors protect from the bone loss in ovariectomy rats by increasing bone vascularity. AB - The hypoxia-inducible factor-1alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) pathway is involved in skeletal development, bone repair, and postmenopausal osteoporosis. Inhibitors of prolyl hydroxylases (PHD) enhance vascularity, increase callus formation in a stabilized fracture model, and activate the HIF-1alpha/VEGF pathway. This study examined the effects of estrogen on the HIF-1alpha/VEGF pathway in osteoblasts and whether PHD inhibitors can protect from bone loss in postmenopausal osteoporosis. Osteoblasts were treated with estrogen, and expressions of HIF-1alpha and VEGF were measured at mRNA (qPCR) and protein (Western blot) levels. Further, osteoblasts were treated with inhibitors of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, and levels of VEGF mRNA and protein expression were detected. In addition, ovariectomized rats were treated with PHD inhibitors, and bone microarchitecture and bone mechanical strength were assessed using micro-CT and biomechanical analyses (lower ultimate stress, modulus, and stiffness). Blood vessel formation was measured with India Ink Perfusion and immunohistochemistry. Estrogen, in a dose- and time-dependent manner, induced VEGF expression at both mRNA and protein levels and enhanced HIF-1alpha protein stability. Further, the estrogen-induced VEGF expression in osteoblasts involved the PI3K/Akt pathway. PHD inhibitors increased bone mineral density, bone microarchitecture and bone mechanical strength, and promoted blood vessel formation in ovariectomized rats. In conclusion, estrogen and PHD inhibitors activate the HIF-1alpha/VEGF pathway in osteoblasts. PHD inhibitors can be utilized to protect bone loss in postmenopausal osteoporosis by improving bone vascularity and angiogenesis in bone marrow. PMID- 24242188 TI - Continuous renal replacement therapy as a supportive treatment for acute pediatric necrotizing fasciitis. AB - Acute necrotizing fasciitis (NF) in children is a dangerous illness characterized by progressive necrosis of the skin and subcutaneous tissue. The present study summarizes our recent experience with the treatment of pediatric patients with severe NF. Between 2000 and 2009, eight children suffering from NF were admitted to our department. Four of the children received an active treatment strategy including continuous renal replacement therapy (CRRT), radical debridement, and broad-spectrum antibiotics. Another four children presented at a late stage of illness, and did not complete treatment. Clinical data for these two patient groups were retrospectively analyzed. The four patients that completed CRRT, radical debridement, and a course of broad-spectrum antibiotics were cured without any significant residual morbidity. The other four infants died shortly after admission. Early diagnosis, timely debridement, and aggressive use of broad spectrum antibiotics are key factors for achieving a satisfactory outcome for cases of acute NF. Early intervention with CRRT to prevent septic shock may also improve patient outcome. PMID- 24242189 TI - Ventricular pacing on the prognosis of patients with pacemaker implantation. AB - Excessive right ventricular apex pacing has significant adverse effects on the cardiac function and hence, it is necessary to clinically optimize pacing parameters and advocate suitable physiological pacing to safeguard the cardiac function after pacemaker implant. Minimizing ventricular pacing is an atrioventricular node priority function, to encourage ventricular self conduction and to reduce unnecessary right ventricular pacing. Minimized ventricular pacing reduces ventricular pacing by encouraging self atrioventricular conduction function and extending the AV interval. This study is a prospective cohort study to evaluate the changes of cardiac function in patients and serum amino-terminal natriuretic peptide (NT-proBNP) before and after pacing, and the risk of atrial fibrillation with different CUM% VP. The study has shown that the cardiac function will deteriorate with an increase in pacing rate. PMID- 24242190 TI - Non-steroidal anti-inflammatory drugs and hypertension. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to alleviate pain of the patients who suffer from inflammatory conditions like rheumatoid arthritis, osteoarthritis, and other painful conditions like gout. This class of drugs works by blocking cyclooxgenases which in turn block the prostaglandin production in the body. Most often, NSAIDs and antihypertensive drugs are used at the same time, and their use increases with increasing age. Moreover, hypertension and arthritis are common in the elderly patients requiring pharmacological managements. An ample amount of studies put forth evidence that NSAIDs reduce the efficiency of antihypertensive drugs plus aggravate pre existing hypertension or make the individuals prone to develop high blood pressure through renal dysfunction. This review will help doctors to consider the effects and risk factors of concomitant prescription of NSAIDs and hypertensive drugs. PMID- 24242184 TI - A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium. AB - Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome. PMID- 24242191 TI - The clinical study of stereotactic microsurgery. AB - The objective of this study is to investigate the operative methods and therapeutic effects of stereotactic-guided microsurgical resection of hypertensive cerebral hemorrhage lesions in functional region. 18 cases of intracranial lesions (diameter 1.5-3 cm) were studied using a Leksell-G stereotactic system. Guided by the CT or MR, a small incision was made and the skull was opened with an annular drill. Electrophysiological stimulation was applied along the non-functional areas. 100 patients with cerebral hemorrhage were randomized into two groups of 50 cases each. One of the groups was treated using microsurgery, while the other group was treated using stereotactic technique. A comparative study was carried out between the two treatment methods for hypertensive intracerebral hemorrhage using the recent (1 month) and long term (6 months) treatment. Using a Leksell-G system for precise positioning of microsurgery, 100 % of the lesion was fully removed. Neurological function was well protected without mortality or neurological deficiency. The use of stereotactic microsurgery for hypertensive intracerebral hemorrhage is successful compared with traditional methods. There is a significant clinical effect on the recovery of neurological function in patients. Stereotactic microsurgical resection of the lesion along with Ribbon treatment of hypertensive cerebral hemorrhage is an accurate, minimally invasive, safe, and effective surgical method. PMID- 24242192 TI - A model for small heat shock protein inhibition of polyglutamine aggregation. AB - Polyglutamine (polyQ) repeat expansions that lead to the formation of amyloid aggregates are linked to several devastating neurodegenerative disorders. While molecular chaperones, including the small heat shock proteins (sHsp), play an important role in protection against protein misfolding, the aberrant protein folding that accompanies these polyQ diseases overwhelms the chaperone network. By generating a model structure to explain the observed suppression of spinocerebellar ataxia 3 (SCA3) by the sHsp alphaB-crystallin, we have identified key vulnerabilities that provide a possible mechanism to explain this heat shock response. A docking study involving a small bioactive peptide should also aid in the development of new drug targets for the prevention of polyQ-based aggregation. PMID- 24242194 TI - The Cochrane Collaboration twenty years on. PMID- 24242195 TI - Bridging the transition from hospital to home: effects of the VITAL telehealth program on recovery for CABG surgery patients and their caregivers. AB - The purpose of this randomized trial was to determine whether coronary artery bypass graft surgery patients and their caregivers who received telehealth follow up had greater improvements in anxiety levels from pre-surgery to 3 weeks after discharge than did those who received standard care. Secondary outcomes included changes in depressive symptoms and patients' contacts with physicians. No group differences were noted in changes in patients' anxiety and depressive symptoms, but patients in the telehealth group had fewer physician contacts (p = .04). Female caregivers in the telehealth group had greater decreases in anxiety than those in standard care (p < .001), and caregivers of both genders in the telehealth group had greater decreases in depressive symptoms (p = .03). PMID- 24242193 TI - Not all GMOs are crop plants: non-plant GMO applications in agriculture. AB - Since tools of modern biotechnology have become available, the most commonly applied and often discussed genetically modified organisms are genetically modified crop plants, although genetic engineering is also being used successfully in organisms other than plants, including bacteria, fungi, insects, and viruses. Many of these organisms, as with crop plants, are being engineered for applications in agriculture, to control plant insect pests or diseases. This paper reviews the genetically modified non-plant organisms that have been the subject of permit approvals for environmental release by the United States Department of Agriculture/Animal and Plant Health Inspection Service since the US began regulating genetically modified organisms. This is an indication of the breadth and progress of research in the area of non-plant genetically modified organisms. This review includes three examples of promising research on non-plant genetically modified organisms for application in agriculture: (1) insects for insect pest control using improved vector systems; (2) fungal pathogens of insects to control insect pests; and (3) virus for use as transient-expression vectors for disease control in plants. PMID- 24242196 TI - Turning over patient turnover: an ethnographic study of admissions, discharges, and transfers. AB - The impact on nursing work of patient turnover (admissions, discharges, and transfers) became evident in an ethnographic study of turbulence. The patient turnover data were generated from extensive observations, 21 formal interviews, and a year of admission and discharge records on one medical and one surgical unit. Timing of turnover events on the two units differed, but on both units admissions typically interrupted workflow more than did discharges, clustered admissions were more disruptive than staggered admissions, and patient turnover during change of shift was more disruptive than during medication administration. Understanding the complexity of patient turnover will elucidate the work involved and improve the evidence base for nurse staffing, a key determinant of quality and safety of care. PMID- 24242197 TI - A structural model of the influence of immigrant mothers' depressive symptoms and home environment on their children's early developmental outcomes in Taiwan. AB - In this cross-sectional study of 61 immigrant mothers and their 6- to 24-month old children in Taiwan, we examined the structure of relationships among maternal depressive symptoms, quality of the child-rearing home environment, and child development using a partial least squares approach. Maternal depressive symptoms as measured by the Edinburgh Postnatal Depression Scale had a direct and negative effect on the quality of the home environment as measured by the IT-HOME, which in turn had a direct and positive effect on child development as measured by the Comprehensive Developmental Inventory for Infants and Toddlers. Maternal depressive symptoms did not directly affect child development, suggesting that the quality of the home environment mediated the relationship between maternal depressive symptoms and child development. PMID- 24242198 TI - New sesquiterpenes fromMaytenus species (Celastraceae). Taxonomic and chemotaxonomic considerations concerning chileanMaytenus. AB - Three new dihydro-beta-agarofuran sesquiterpenes from two species ofMaytenus were isolated and their structures were elucidated by means of(1)H and(13)C NMR studies. The differences and similarities noted in the chemical content of the dihydro-beta-agarofuran sesquiterpenes from the fourMaytenus species from Chile are in line with the taxonomic characterization of these species; their geographical distribution is also given. PMID- 24242199 TI - Influence of white pine watering regimes on feeding preferences of spring and fall adults of the white pine weevilPissodes strobi (Peck). AB - Spring and fall adults of the white pine weevil,Pissodes strobi (Peck), were exposed in no-choice and two-choice tests to bark from water-stressed and non water-stressed white pine (Pinus strobus L.), which had also been exposed or not exposed to weevil attack. This experiment demonstrated that the weevils could discriminate between bark from water-stressed white pine and preferred bark from the nonstressed plants. The weevils also preferred bark from nonstressed plants that were previously exposed to weevil damage. Spring and fall adults displayed the same feeding preferences. No sex differences were found in feeding preferences. Less nitrogen, phosphorus, and potassium were found in bark from the nonstressed plants, and the potassium level was higher in damaged plants. We expect that the biological performance of the weevil should be favored by vigorously growing plants rather than by stressed plants. PMID- 24242200 TI - Elevational variation of quinolizidine alkaloid contents in a lupine (Lupinus argenteus) of the Rocky Mountains. AB - Quinolizidine alkaloid contents of leaves and seeds ofLupinus argenteus (Fabaceae) collected from seven different localities near Gothic, Colorado were determined by capillary GLC. Differences in alkaloid levels between sites are substantial and alkaloid quantity decreases as elevation increases. Leaves at the lowest elevation, for example, contain six times the alkaloid levels of leaves at the highest elevation. Seeds from plants of low-and high-elevation sites were grown under identical conditions in the green-house. Alkaloid levels of leaves of seedlings were significantly higher in those seedlings derived from populations of low elevations than those of high elevations, indicating that the observed differences in the field are at least partly genetic and not environmental. To determine whether predation rates were responsible for these genetic differences, data on seed predation rates and observations on herbivory were collected. PMID- 24242201 TI - Chemotactic tube-foot responses of a spongivorous sea starPerknaster fuscus to organic extracts from antarctic sponges. AB - Hexane, chloroform, and methanol extracts of 18 species of antarctic sponges were tested for their ability to induce sustained tube-foot retraction in the antarctic spongivorous sea starPerknaster fuscus. Extracts were imbedded in silicone and used to coat the tip of a glass rod, which was allowed to contact an extended tube-foot. Retraction times were measured and compared with three controls: contact with a glass rod coated with a hexane extract of fish (feeding stimulant), contact with the glass rod alone (mechanical control), and contact with the glass rod coated with silicone alone (silicone control). Only extracts of the spongeMycale acerata did not elicit significantly longer tube-foot retraction times than controls for at least one of the three organic extracts. Hexane sponge extracts elicited the lowest levels of significant tube-foot responses, with only 39% of the sponge species tested showing activity in this fraction. In contrast, chloroform and methanol extracts elicited a significant tube-foot retraction response in 73% and 78% of the species tested, respectively. This indicates that in this assay repellent metabolites are generally more polar substances. It remains to be determined that secondary metabolites are responsible for all of the tube-foot retraction responses detected in sea stars exposed to sponge extracts; bioactive secondary metabolites have been isolated from a number of these antarctic sponges. It may be of ecological significance that the two rapidly growing sponges,Homaxinella balfourensis andMycale acerata, were either not repellent or had low repellency, and thatM. acerata is the primary dietary item ofPerknaster fuscus. PMID- 24242202 TI - Mating disruption of pea mothCydia nigricana F. (lepidoptera: Tortricidae) by a repellent blend of sex pheromone and attraction inhibitors. AB - Synthetic sex pheromone of the pea mothCydia nigricana, (E,E)-8,10-dodecadien-1 yl acetate (E8,E10-12: Ac), was applied in polyethylene dispensers at a rate of 30 g/ha and 600 dispensers/ha in a 0.6-ha pea field. The release rate ofE8,E10 12: Ac was 140 mg/ha/day after six days, and 82 mg/ha/day after 20 days. Aerial concentrations ofE8,E10-12: Ac, as measured by a portable EAG apparatus, ranged from 2 +/- 2 to 7 +/- 3 ng/m(3). The antennal signal was high and rather constant within pea canopy, but was lower and fluctuated strongly above canopy. Initially, >99% isomerically pureE8,E10-12: Ac was released, and male moths were attracted to dispensers. After nine days, isomeric blend composition had equilibrated to approx. 92%E8,E10-12: Ac and 8% of the inhibitory isomersE,Z-,Z,E-, andZ8,Z10-12: Ac. Males were then repelled from the pheromone-permeated field. Traps baited with 100 ugE8,E10-12: Ac caught 258 +/- 133C. nigricana males/trap in the control, but no males at all in the disruption field. PMID- 24242203 TI - Ethyl propionate: Synergistic kairomone for african palm weevil,Rhynchophorus phoenicis L. (Coleoptera: Curculionidae). AB - Small trunk pieces of a freshly felled 10-year-old oil palm,Elaeis quineensis (Jacq.), were placed in a modified Nalgene desiccator, and volatiles captured for six days on Porapak Q. Gas chromatographic (GC) analysis of Porapak-Q-trapped volatiles with both flame ionization (FID) and electroantennographic detection (EAD) using male or femaleR. phoenicis antennae revealed several EAD-active compounds. They were identified as: ethyl acetate, ethyl propionate, isobutyl propionate, ethyl butyrate, and ethyl isobutyrate. In field experiments in the La Me Research Station, Cote d'Ivoire, ethyl propionate (50 mg/24 hr) but not all esters combined (50 mg/24 hr each) significantly increased capture ofR. phoenicis in pheromone-baited (3 mg/24 hr) traps. One kilogram of 1- to 3-day-old palm tissue was significantly more effective than ethyl propionate in enhancing pheromone attraction. Superior attraction of palm tissue may be attributed to additional as yet unknown semiochemicals. Alternatively, release rates and/or ratios of synthetic volatiles differed from those of palm tissue at peak attraction. PMID- 24242204 TI - Repellent, toxic, and food protectant effects of pithraj,Aphanamixis polystachya extracts against pulse beetle,Callosobruchus chinensis in storage. AB - Ground leaves, bark, seeds, and four seed extracts of pithraj,Aphanamixis polystachya (family Meliaceae), a locally grown plant in Bangladesh, were evaluated for their repellency, contact toxicity, and food protectant efficacy against adult pulse beetle (Callosobruchus chinensis L.). The seed extracts showed poor repellent effects, but high contact toxicity to adults at 72 hr after application. The ground leaves, bark, and seeds provided good protection for mung beans against pulse beetles, and the seed powder greatly reduced the F1 progeny and seed damage rates. PMID- 24242205 TI - Quantification of electroantennogram responses of the primary rhinaria ofAcyrthosiphon pisum (Harris) to C4-C 8 primary alcohols and aldehydes. AB - Electroantennograms (EAGs) of the distal and proximal primary rhinaria (DPR and PPR, respectively) were recorded from excised antennae of alate virginoparous pea aphids,Acyrthosiphon pisum (Harris) (Homoptera: Aphididae). Primary unsaturated alcohols and aldehydes with varying carbon length (C4-C8) were used as volatile stimuli. EAGs were recorded for a series of source concentrations from the DPR and PPR separately through the use of sectional electroantennography. A logistic equation was fitted to the source concentration-response data. Differences in relative EAG response of the DPR and PPR to the alcohols and aldehydes were analyzed by deriving five parameters from this logistic equation. These parameters relate to particular characteristics of sigmoid curves: the saturation (maximum) EAG response (R s ), the concentration for which the relative EAG response is 1/2R s (CR50), the stimulus response range (SR 0.9), the threshold concentration (CR1), and the EAG response area (A R ). Of these parameters, the EAG response area showed the largest separation between EAG responses of the DPR and PPR to the two homologous groups and between compounds with varying carbon chain lengths. The DPR was significantly more responsive to alcohols than to aldehydes, while the reverse was true for the PPR, indicating a basic difference between the two primary rhinaria. The highest overall responses were elicited by 1-hexanol, hexanal, and heptanal. PMID- 24242206 TI - Influence of cnicin, a sesquiterpene lactone ofCentaurea maculosa (Asteraceae), on specialist and generalist insect herbivores. AB - The sesquiterpene lactone cnicin was extracted fromCentaurea maculosa andCentaurea vallesiaca. We examined its effects on the ovipositional response and larval development of generalist and specialist insect herbivores associated withC. maculosa. For the oviposition trials, three plant species (C. maculosa, Achillea millefolium, andCichorium intybus), half of which were sprayed with 3% of cnicin, were exposed to the specialist mothsStenodes straminea, Agapeta zoegana, andPterolonche inspersa in field cages. All three species significantly preferredC. maculosa to other plants andP. inspersa significantly preferred cnicin-sprayed plants to untreated plants for oviposition. Tested over all species, cnicin significantly increased the number of eggs laid on a given plant. A larval diet test examined the toxicity of cnicin for larvae of the generalist noctuid mothSpodoptera littoralis. Cnicin concentrations of 3% and 6% were lethal and 1% and 0.5% seriously inhibited growth and development. The larvae of theC. maculosa specialistStenodes straminea survived at 6% cnicin, but none of the pupae hatched.Agapeta zoegana was able to survive at 1% and 3% cnicin. Both specialists had difficulties with the artificial diet, but weight increase and survival was not further reduced when cnicin was present compared with on the control diet. In conclusion, cnicin influenced host recognition by the specialist species, and larvae of the generalist did not survive on natural levels of cnicin. Growth and survival of the specialist were not influenced by cnicin but were considerably hampered on artificial diet. PMID- 24242207 TI - Dietary source for skin alkaloids of poison frogs (Dendrobatidae)? AB - A wide range of alkaloids, many of which are unknown elsewhere in nature, occur in skin of frogs. Major classes of such alkaloids in dendrobatid frogs are the batrachotoxins, pumiliotoxins, histrionicotoxins, gephyrotoxins, and decahydroquinolines. Such alkaloids are absent in skin of frogs (Dendrobates auratus) raised in Panama on wingless fruit flies in indoor terraria. Raised on leaf-litter arthropods that were collected in a mainland site, such terraria raised frogs contain tricyclic alkaloids including the beetle alkaloid precoccinelline, 1,4-disubstituted quinolizidines, pyrrolizidine oximes, the millipede alkaloid nitropolyzonamine, a decahydroquinoline, a gephyrotoxin, and histrionicotoxins. The profiles of these alkaloids in the captive-raised frogs are closer to the mainland population ofDendrobates auratus at the leaf-litter site than to the parent population ofDendrobates auratus from a nearby island site. Extracts of a seven-month sampling of leaf-litter insects contained precoccinelline, pyrrolizidine oxime236 (major), and nitropolyzonamine (238). The results indicate a dietary origin for at least some "dendrobatid alkaloids," in particular the pyrrolizidine oximes, the tricyclic coccinellines, and perhaps the histrionicotoxins and gephyrotoxins. PMID- 24242208 TI - A growth inhibitory factor from lambsquarters (Chenopodium album). AB - Aqueous extract of air-dried lambsquarters (Chenopodium album) at 25 mg/ml significantly inhibited germination and growth of radish and wheat seeds. Soybean seed germination was not inhibited; however, hypocotyl growth was significantly reduced. Germination of radish seeds in sand amended with pulverized lambsquarters shoots at 2 and 4 mg/g was reduced 40 and 95%, respectively. Shoot dry weight and plant height were also reduced 30 and 9%, respectively, at 4 mg/g, but not at 2 mg/g concentration. Residues after extraction with water incorporated in sand were not inhibitory, indicating water solubility of the inhibitor(s). Aqueous extract of shoots decomposed for five days lost nearly 40% of its inhibitory effect; 20% of it still persisted in the extract of shoots decomposed for 30 days. The filtrate from ultrafiltration of aqueous extract through a pad of molecular-weight cutoff 1000 inhibited radish seeds germination and growth, indicating that the molecular weight of the inhibitor(s) was less than 1000. Partitioning of the aqueous extract by a series of solvents resulted in isolation of an inhibitor(s) in the butanol fraction. Seven phenolics were identified in this fraction using high-performance liquid chromatography (HPLC). Paper chromatographic analysis of the butanol fraction revealed six bands, of which one band withR f =0.83 inhibited germination and growth of radish seeds. Chlorogenic acid identified by HPLC appeared to be the principal component of the phytotoxin. PMID- 24242209 TI - Effects of two sesquiterpene lactones isolated fromArtemisia annua on physiology ofLemna minor. AB - The effects of artemisinin and arteannuic acid extracted fromArtemisia annua on the physiology ofLemna minor were evaluated. Changes in frond production, growth, dry weight, and chlorophyll content ofL. minor were determined. Photosynthesis and respiration were evaluated with a differential respirometer. Artemisinin (5 uM) inhibitedL. minor frond production and dry weight 82 and 83%, relative to methanol controls. Chlorophyll content was reduced 44% by artemisinin (2.5 uM). Arteannuic acid (10 uM) was less active, inhibiting frond production 61% and reducing chlorophyll content 66% at 5 uM. Artemisinin (1 uM) reducedL. minor photosynthesis 30% and 2.5 uM reduced respiration 39%. Arteannuic acid had no significant effect on photosynthesis or respiration at the levels tested. PMID- 24242210 TI - Pulsed radiofrequency reduced complete Freund's adjuvant-induced mechanical hyperalgesia via the spinal c-Jun N-terminal kinase pathway. AB - Pulsed radiofrequency (PRF) treatment involves the pulsed application of a radiofrequency electric field to a nerve. The technology offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA) induced inflammatory pain. The profile of spinal c-Jun N-terminal kinases (JNKs) phosphorylation was evaluated to elucidate the potential mechanism. Injection of CFA into the unilateral hind paw of rats induced mechanical hyperalgesia in both the ipsilateral and contralateral hind paws. We administered 500-kHz PRF treatment in 20-ms pulses, at a rate of 2 Hz (2 pulses per second) either to the sciatic nerve in the mid-thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen in both the CFA group and no-PRF group rats. Tissue samples were examined at 1, 3, 7, and 14 days following PRF treatments. Behavioral studies showed that PRF applied close to the dorsal root ganglion (DRG) significantly attenuated CFA-induced mechanical hyperalgesia compared to no-PRF group (P < .05). And western blotting revealed significant attenuation of the activation of JNK in the spinal dorsal horn compared to no-PRF group animals (P < .05). Application of PRF close to DRG provides an effective treatment for CFA-induced persistent mechanical hyperalgesia by attenuating JNK activation in the spinal dorsal horn. PMID- 24242212 TI - The bispecific immunoligand ULBP2-aCEA redirects natural killer cells to tumor cells and reveals potent anti-tumor activity against colon carcinoma. AB - NKG2D, an activating receptor expressed on NK cells and T cells, is critically involved in tumor immunosurveillance. In this study, we explored the potential therapeutic utility of the NKG2D ligand ULBP2 for the treatment of colon carcinoma. To this end we designed a fusion protein consisting of human ULBP2 and an antibody-derived single chain targeting the tumor carcinoembryonic antigen (CEA). The bispecific recombinant fusion protein re-directed NK cells towards malignant cells by binding to both, tumor cells and NK cells, and triggered NK cell-mediated target cell killing in vitro. Moreover, tumor growth was significantly delayed in a syngeneic colon carcinoma mouse model in response to immunoligand treatment. The anti-tumor activity could be attributed to the stimulation of immune cells with an elevated expression of the activation marker CD69 on NK, T and NKT cells and the infiltration of CD45+ immune cells into the solid tumor. In summary, it was demonstrated that immunoligands provide specific tumor targeting by NK cells and exert anti-tumor activity in vitro and in vivo. This technology represents a novel immunotherapeutic strategy for solid tumors with the potential to be further developed for clinical applications. PMID- 24242211 TI - Integrating DNA methylation dynamics into a framework for understanding epigenetic codes. AB - Genomic function is dictated by a combination of DNA sequence and the molecular mechanisms controlling access to genetic information. Access to DNA can be determined by the interpretation of covalent modifications that influence the packaging of DNA into chromatin, including DNA methylation and histone modifications. These modifications are believed to be forms of "epigenetic codes" that exist in discernable combinations that reflect cellular phenotype. Although DNA methylation is known to play important roles in gene regulation and genomic function, its contribution to the encoding of epigenetic information is just beginning to emerge. Here we discuss paradigms associated with the various components of DNA methylation/demethylation and recent advances in the understanding of its dynamic regulation in the genome, integrating these mechanisms into a framework to explain how DNA methylation could contribute to epigenetic codes. PMID- 24242213 TI - Comparing time to adverse drug reaction signals in a spontaneous reporting database and a claims database: a case study of rofecoxib-induced myocardial infarction and rosiglitazone-induced heart failure signals in Australia. AB - INTRODUCTION: The objective of post-marketing surveillance of medicines is to rapidly detect adverse drug reactions (ADRs). Early ADR detection will enable policy makers and health professionals to recognise adverse events that may not have been identified in pre-marketing clinical trials. Multiple methods exist for ADR signal detection. Traditional quantitative methods employed in spontaneous reports data have include reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian techniques. With the development of administrative health claims databases, additional methods such as sequence symmetry analysis (SSA) may be able to be employed routinely to confirm ADR signals. OBJECTIVE AND METHOD: We tested the time to signal detection of quantitative ADR signalling methods in a health claims database (SSA) and in a spontaneous reporting database (ROR, PRR, Bayesian confidence propagation neural network) for rofecoxib-induced myocardial infarction and rosiglitazone-induced heart failure. RESULTS: This study demonstrated that all four signalling methods detected safety signals within 1-3 years of market entry or subsidisation of the medicines, and for both cases the signals were detected before post-marketing clinical trial results. By contrast, the trial results and subsequent warning or withdrawal were published 5 7 years after first marketing of these medicines. CONCLUSION: This case study highlights that a post-marketing quantitative method utilising administrative claims data can be a complementary tool to traditional quantitative methods employed in spontaneous reports that may help to verify safety signals detected in spontaneous reporting data. PMID- 24242214 TI - NMDA-R inhibition affects cellular process formation in Tilapia melanocytes; a model for pigmented adrenergic neurons in process formation and retraction. AB - Parkinson's disease has long been described to be a product of dopamine and (or) melanin loss in the substanstia nigra (SN). Although most studies have focused on dopaminergic neurons, it is important to consider the role of pigment cells in the etiology of the disease and to create an in vitro live cell model for studies involving pigmented adrenergic cells of the SN in Parkinsonism. The Melanocytes share specific features with the pigmented adrenergic neurons as both cells are pigmented, contain adrenergic receptors and have cellular processes. Although the melanocyte cellular processes are relatively short and observable only when stimulated appropriately by epinephrine and other factors or molecules. This study employs the manipulation of N-Methyl-D-Aspartate Receptor (NMDA-R), a major receptor in neuronal development, in the process formation pattern of the melanocyte in order to create a suitable model to depict cellular process elongation and shortening in pigmented adrenergic cells. NMDA-R is an important glutamate receptor implicated in neurogenesis, neuronal migration, maturation and cell death, thus we investigated the role of NMDA-R potentiation by glutamate/KCN and its inhibition by ketamine in the behavior of fish scale melanocytes in vitro. This is aimed at establishing the regulatory role of NMDA-R in this cell type (melanocytes isolated form Tilapia) in a similar manner to what is observable in the mammalian neurons. In vitro live cell culture was prepared in modified Ringer's solution following which the cells were treated as follows; Control, Glutamate, Ketamine, Glutamate + Ketamine, KCN + Ketamine and KCN. The culture was maintained for 10 min and the changes were captured in 3D-Time frame at 0, 5 and 10 min for the control and 5, 7 and 10 min for each of the treatment category. Glutamate treatment caused formation of short cellular processes localized directly on the cell body while ketamine treatment (inhibition of NMDA R) facilitated elongation of secondary cellular processes (highly branched) from primary major processes (Less branched); co-incubation of glutamate and ketamine induced short and highly branched process formation. Cyanide toxicity induced degeneration and reduction of cell size while co-treatment of cyanide and ketamine gave changes similar to that observed in glutamate-ketamine co incubation. NMDA-R is present in the melanocytes. Activation of the receptor reduced elongation process, while inhibition of the receptor facilitated cell process elongation and branching. This confirms that like pigmented adrenergic cells of the nervous system, this cell contains NMDA-R and this receptor also regulates cell process elongation. The study also showed that inhibition of NMDA R in melanocytes gave opposite outcomes to the role of the receptor in developing neurons; a function that is protective in adult neurons. PMID- 24242215 TI - Multiple myeloma recurrence with optic nerve infiltration diagnosed by vitrectomy, immunohistochemistry, and in situ hybridization. AB - PURPOSE: We present a case of multiple myeloma recurrence diagnosed by optic nerve infiltration. METHODS: Interventional case report with clinical, surgical, immunohistochemical, and fluorescence in situ hybridization correlation. RESULTS: A 51-year-old woman with a history of bilateral invasive ductal breast carcinoma and multiple myeloma, both in remission on maintenance bortezomib, was referred for sudden, painless loss of vision OS. Examination demonstrated anterior vitritis with severe optic disc elevation, with yellow-white thickening, peripapillary hemorrhages, and a retinal detachment inferiorly. Diagnostic vitrectomy showed CD138-positive and BRST2-negative cells. Fluorescence in situ hybridization was positive for del(13q) and p53 deletion and negative for CCND1/IGH. CONCLUSIONS: This is the first report of optic nerve infiltration of multiple myeloma as evidence of recurrence while on maintenance chemotherapy. We demonstrate that diagnostic vitrectomy and immunohistochemistry of vitreous fluid is feasible for the diagnosis of recurrent multiple myeloma. PMID- 24242216 TI - Clinical features of patients with episcleritis and scleritis in an Italian tertiary care referral center. AB - PURPOSE: To evaluate demographic characteristics, clinical features, systemic disease associations, visual outcomes, and treatment modalities of patients with episcleritis and scleritis in an Italian tertiary care referral center. METHODS: Data from 25 patients with episcleritis and from 85 patients with scleritis followed from 2003 to 2012 were retrospectively evaluated. The main outcome measures were demographics, ocular disease characteristics, presence of systemic associated disease, treatment regimen, and follow-up period. RESULTS: Episcleritis and scleritis were found bilaterally in 24% and 31% of patients, respectively (p<0.521). The episcleritis was diffuse in 15 and focal in 10 patients, while the scleritis was diffuse in 49, nodular in 28, necrotizing in 6, and posterior in 2 patients. Anterior uveitis (4% vs 31%; p<0.006), peripheral ulcerative keratitis (0% vs 14%; p<0.167), ocular hypertension (0% vs 7%; p<0.333), and a decrease in visual acuity (4% vs 19%; p<0.112) were encountered as ocular complications in patients with episcleritis and patients with scleritis, respectively. An associated systemic disease was found in 20% and 52% of patients with episcleritis and patients with scleritis (p<0.004). Among patients with episcleritis, 76% required topical corticosteroid treatment to achieve disease resolution, 16% oral nonsteroidal anti-inflammatory drugs (NSAIDs), and 8% antivirals; 39% of patients with scleritis required systemic NSAIDs, 12% oral corticosteroids, 34% immunosuppressive drugs, and 15% antibiotics or antivirals. CONCLUSIONS: The importance of differentiating scleritis from episcleritis is remarkable given the significant difference in the degree of ocular complications and associated systemic diseases between these ocular conditions. Prompt diagnosis, systemic assessment, and treatment are fundamental in all patients with scleral inflammation. PMID- 24242217 TI - Intravitreal anti-VEGF therapy for vascularized pigment epithelium detachment in age-related macular degeneration. AB - PURPOSE: To assess the efficacy of intravitreal anti-vascular endothelial growth factor (VEGF) treatment of vascularized pigment epithelial detachment (PED) due to age-related macular degeneration (AMD). METHODS: A total of 26 patients with vascularized PED secondary to AMD were retrospectively analyzed and treated with anti-VEGF intravitreal injections according to a PRN regimen after 3 initial injections. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein angiography were performed at baseline and quarterly. RESULTS: Mean follow-up ranged from 9 to 26 months (mean 13.5). There was a deterioration in mean BCVA from 0.46 at baseline to 0.79 logMAR at 12 months (p<0.001). The mean PED greatest linear diameter (GLD) increased from 4499 at baseline to 5206 MUm at 1-year follow-up (p<0.001). The mean PED maximum height decreased from 669 MUm at baseline to 305 MUm at 1-year follow-up (p = 0.001). The mean central retinal thickness (CRT) was unchanged (from 277 to 209 MUm at 1 year follow-up) (p = 0.099). No effect was seen on the change of VA according to groups of baseline predictors as defined by the medial value: baseline VA, PED height, and CRT (p>0.10).There was a borderline trend (p = 0.064) that GLD affected response to treatment. The mean number of injections was 5.5 (3 to 9). Seven out of 26 (27%) patients developed a retinal pigment epithelium (RPE) tear. CONCLUSIONS: Intravitreal anti-VEGF therapy, with a PRN regimen, did not prevent visual acuity loss or RPE tear. PMID- 24242218 TI - Visian toric ICL implantation after intracorneal ring segments implantation and corneal collagen crosslinking in keratoconus. AB - PURPOSE: To evaluate the safety and clinical outcome of Visian toric implantable collamer lens (TICL) implantation for the treatment of residual refractive errors 6 months after sequential intracorneal ring segments (ICRS) and corneal collagen UVA crosslinking (CXL) in stable keratoconus. METHODS: This retrospective study examined the results of a 3-step ICRS-CXL-TICL in 11 eyes of 7 patients with moderate to severe keratoconus. The 2 procedures (ICRS-CXL) were performed sequentially at an interval of 4 weeks and TICL implantation was performed at least 6 months after CXL. Data were collected preoperatively, at the 6-month follow-up visit after sequential ICRS-CXL, and at the 6-month follow-up visit after TICL implantation. RESULTS: The ICRS-CXL induced a significant decrease in keratometry, increase in visual acuity, and decrease in refraction. At 6-month follow-up after ICRS-CXL, mean Kflat was 45.19 +/- 3.98 D vs 48.51 +/- 4.26 D preoperatively (p = 0.022) and mean Ksteep was 50.41 +/- 4.32 D vs 54.24 +/- 4.96 D preoperatively (p = 0.032). Uncorrected distance visual acuity (UCVA) significantly improved from 1.47 +/- 0.38 logMAR before ICRS-CXL to 0.27 +/- 0.20 logMAR 6 months after (p = 0.002). Corrected distance visual acuity (CDVA) significantly improved from 0.50 +/- 0.22 logMAR to 0.29 +/- 0.23 logMAR (p = 0.001). At 6 months post TICL implantation, UCVA improved significantly to 0.27 +/- 0.20 logMAR and the CDVA was 0.19 +/- 0.11 logMAR. No intraoperative or postoperative complications occurred. CONCLUSIONS: Toric ICL implantation after sequential ICRS implantation and CXL is an effective and safe option for correcting high residual refractive error and improving visual acuity in patients with moderate to severe keratoconus. PMID- 24242219 TI - The effect of subconjunctival ranibizumab on corneal and anterior segment neovascularization: study on an animal model. AB - PURPOSE: To evaluate the effect of subconjunctival anti-vascular endothelial growth factor (VEGF) ranibizumab on corneal and anterior segment neovascularization. METHODS: In this experimental study and laboratory investigation, chemical cauterization was utilized to induce corneal neovascularization in 16 rabbits randomly divided in 2 equal groups. Cauterized eyes were either treated with 0.1 mL (1 mg) of subconjunctival ranibizumab or administered a sham injection. A third group of 4 rabbits served as control for side effects after ranibizumab administration. All animals were monitored daily for 14 days and the extent of corneal scarring and neovascularization was measured on days 1, 7, and 14. After enucleation, ocular tissues were separated under a surgical microscope and VEGF levels were measured with ELISA. Statistical analysis was performed to compare the extent of corneal neovascularization and VEGF levels between treated and untreated eyes. RESULTS: Subconjunctival ranibizumab inhibited corneal neovascularization significantly both in the first and the second week compared to untreated controls (p = 0.006 and p = 0.001, respectively). The VEGF levels were significantly lower in all anterior segment tissues like the cornea, iris, aqueous humor, and conjunctiva of the treated eyes (p<0.01). The reduction of VEGF levels ranged from 19% to 73% in different ocular tissues. Corneal scarring was not significantly affected by anti-VEGF treatment (p = 0.7). No side effects were noticed. CONCLUSIONS: Early subconjunctival administration of ranibizumab may successfully inhibit alkali-induced corneal neovascularization in an animal model. Subconjunctival ranibizumab reduces VEGF levels significantly not only in the cornea and the bulbar conjunctiva but also in the aqueous humor and the iris. PMID- 24242220 TI - Cataract formation: a possible complication of intra-arterial chemotherapy for retinoblastoma. AB - PURPOSE: To delineate and discuss a not yet described possible ocular complication of selective intra-arterial chemotherapy (SIAC) for treatment of retinoblastoma. METHODS: A 23-month-old girl with a large unilateral retinoblastoma was treated with repeated SIAC using 5 mg melphalan between July 2010 and January 2012. Clinical course of tumor and further ocular changes after therapy and histopathologic findings are described. RESULTS: In total, 5 SIAC were performed over a time period of 18 months. After the last SIAC, diffuse dense cataract prevented further funduscopy. In addition, anterior chamber seeding was obvious, leading to the decision to enucleate the eye. Histopathologically, nearly complete regression of the main tumor mass with prominent calcifications, but vital tumor seeding in the vitreous, on the lens surface, on the ciliary body, and in the anterior chamber, was observed. Peculiar vacuolation of the lens epithelial cells, liquefaction of the subepithelial lens fibers, and diffuse small vacuoles within the lens were striking. CONCLUSIONS: Repeated SIAC with melphalan may induce cataract formation, possibly as a toxic effect of the chemotherapeutic to the lens, maybe combined with radiation exposure during fluoroscopy. This ocular complication should be taken into consideration as a limitation of the number of feasible repeated treatments. PMID- 24242221 TI - Efficacy of transscleral diode laser cyclophotocoagulation in patients with good visual acuity. AB - PURPOSE: To study the effect on central vision of transscleral diode laser cyclophotocoagulation (TSDLC) for the reduction of intraocular pressure (IOP) in patients with visual acuity (VA) better than 6/18. METHODS: Retrospective chart review was conducted of patients undergoing cyclophotocoagulation between 2000 and 2008. Patients who underwent TSDLC with VA of 6/18 or better and at least 24 months follow-up were included. Primary outcome was decrease of 2 or more lines at 24 months. Secondary outcome was IOP control with or without treatment. RESULTS: A total of 46 eyes of 44 patients were included with VA ranging from 6/18 to 6/5 (median VA 6/12). Mean IOP was 24 mm Hg (range 12-35). A mean of 1.3 treatments were given per eye, with 12 eyes (26%) requiring retreatment. At 24 months, the median VA was 6/18 (range light perception-6/5). Eighteen eyes (39.1%) retained the same VA, 35 eyes (76.1%) retained VA of 6/18 or better, in 7 eyes (19.4%) VA was <6/60. Loss of >=2 lines was recorded in 11 eyes (23.9%), and loss of 1 line in 13 eyes (28.3%). Mean IOP at 24 months was 17.2 mm Hg (range 12 28). Thirty-nine (84.8%) patients had IOP <=21 mm Hg. CONCLUSIONS: This study suggests a role of TSDLC as an effective, safe, and rapid method of treatment in patients with good vision over a 24-month period. The loss of VA in some patients is similar to previously reported studies in patients having cyclodiode, trabeculectomy, or tube surgery. PMID- 24242222 TI - One-year outcome of ranibizumab for neovascular age-related macular degeneration: a thorough analysis in a real-world clinical setting. AB - PURPOSE: To verify the safety and efficacy of ranibizumab in neovascular age related macular degeneration (nAMD) and factors influencing the outcome in a real world setting. METHODS: Retrospective 12-month follow-up analysis of 100 naive nAMD eyes treated with as-needed ranibizumab. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), lesion, and leakage size were recorded. Type and characteristics of lesions and indicators of protocol adherence were analyzed. RESULTS: Mean BCVA at baseline was 61.6 +/- 14.8 Early Treatment Diabetic Retinopathy Study letters and 59.6 +/- 16 at 12 months. Sixty three eyes maintained or improved BCVA; the number of injections and follow-up visits were 4.8 and 5.1, respectively. First injection and pro re nata retreatments were administered 22.7 and 20.5 days after prescription, respectively. Seventy-two eyes received 3 initial monthly injections. Patients were not reinjected despite BCVA loss >5 letters one or more times in 37% of cases. No adverse events were reported. The CRT diminished by 26 +/- 101 MUm; choroidal neovascularization size and leakage area increased by 0.53 +/- 1.31 mm2 and 0.34 +/- 1.33 mm2, respectively. The BCVA gain was correlated with CRT reduction (r = 0.24, p = 0.016), mean baseline BCVA (r = -0.25, p = 0.01), age (r = -0.25, p = 0.01), and decrease in CNV size and leakage area (r = 0.56 and r = 0.59, respectively, p<0.001). CONCLUSIONS: Our results compare unfavorably with those of controlled trials. Treatment and follow-up regimens in real-world settings seem to have a major role in determining outcome. Lower age and BCVA at baseline were associated with better response to treatment. PMID- 24242223 TI - Increased central corneal thickness in patients with Turner syndrome. AB - PURPOSE: To evaluate central corneal thickness (CCT) values in patients with Turner syndrome (TS) and compare these values with healthy subjects. METHODS: A total of 31 subjects with TS and 67 age- and sex-matched healthy subjects made up the study and control group, respectively. The CCT values were measured by an ultrasound pachymeter in this cross-sectional prospective study. The ocular findings were recorded. We also evaluated to effect of karyotype analysis, recombinant growth hormone therapy (GHT), and mean duration of treatment on the CCT parameter in patients with TS. RESULTS: The mean CCT values were 582.0 +/- 40.8 um (490-648) in the TS and 549.1 +/- 34.6 um (494-601) in the healthy group. The mean intraocular pressure (IOP) by Goldmann applanation tonometry was 16.3 +/ 3.1 mm Hg (9-22) in the TS and 15.2 +/- 2.5 mm Hg (10-21) in the healthy group. The mean CCT value was significantly higher in the TS group (p<0.05) but there was no statistically significant difference between the 2 groups for IOP (p>0.05). There was also no significant difference for CCT regarding the karyotype, GHT use, and mean duration of treatment in patients with TS (p>0.05). CONCLUSIONS: Central corneal thickness values should be considered during measurement of IOP in individuals with TS as these values may be higher than in healthy subjects. PMID- 24242224 TI - Spectral-domain optical coherence tomography features in fellow eyes of patients with idiopathic macular hole. AB - PURPOSE: To describe the vitreomacular interface and foveal structural changes in fellow eyes of patients with idiopathic macular holes using spectral-domain optical coherence tomography (SD-OCT). METHODS: Retrospective analysis of consecutive medical records and SD-OCT images of the fellow eyes of patients with macular hole was done. Changes of the vitreoretinal interface and foveal structures on SD-OCT scan of the 101 fellow eyes of 101 subjects with full thickness macular hole were studied and compared with 101 eyes of 101 age-matched healthy subjects. RESULTS: Sixty-four patients (57.65%) were female. Mean age at presentation was 60.44 +/- 12.17 years. The best-corrected visual acuity (BCVA) in eyes with macular hole was 0.86 logMAR units and in fellow eyes was 0.41 logMAR units. Seven eyes had macular hole in the fellow eye at the time of presentation. The majority of the fellow eyes (87/101, 78.37%) were phakic. The average base diameter of macular hole was 1105 +/- 451.63 um. Incidence of vitreomacular traction, epiretinal membrane, lamellar hole, and inner foveal split was more common (<0.05) in fellow eyes in comparison to healthy eyes. In contrast, posterior vitreous detachment (PVD) and perifoveal PVD was more common in age-matched control eyes. There was no statistically significant correlation between foveal abnormalities of fellow eyes with base diameter of eyes with macular hole, BCVA, and duration of symptoms. CONCLUSIONS: Fellow eyes of patients with idiopathic macular hole have a high frequency of abnormal vitreoretinal interface and foveal abnormalities, which predisposes to formation of macular hole. PMID- 24242225 TI - Occupational mobility and depression among the foreign-born in the United States. AB - This paper used the 2003 New Immigrant Survey (n = 2,305) to examine the relationship between occupational mobility before and after migration and depression among immigrants. There were two measures of occupational mobility, change in occupational prestige and educational match. For both measures, upward and downward mobility were associated with higher depression. This association was only present among women; for men, there were no significant relationships between the occupational mobility measures and depression. The findings suggest that immigrant occupational mobility may not solely represent the acquisition or reduction of material resources. Instead, occupational mobility may encompass immigrants' unique stressors and post-migration working environments that produce a range of psychosocial influences on mental health. Gender differences also suggest immigrant women face unique stressors that arise from adjusting to both the working and domestic spheres. PMID- 24242226 TI - Impact of economic labour migration: a qualitative exploration of left-behind family member perspectives in Sri Lanka. AB - Sri Lanka is a major labour sending country in Asia, with a high proportion of female labour migrants employed as domestic housemaids in the Middle East with increasing remittances. Despite such financial gains for families and national economy, health and social effects on the left-behind families have had limited exploration. This qualitative study was carried out across five districts with high labour migration rates in Sri Lanka. Twenty in-depth interviews were conducted with participants recruited through purposive sampling. Data was analysed using content and thematic analysis and emerging themes were mapped. Pre migration socio-economic situation, economic difficulties and higher earning possibilities abroad were considered to be the major push and pull factors for labour migration. Post-migration periods were shown to be of mixed benefit to left-behind families and children suffer the negative effects of parental absence. The absence of support mechanisms for dealing with adverse events such as serious injury, death, abuse or imprisonment were cited as major concerns. Post-migration periods affect the health, well-being and family structures of left-behind families. Promoting economic prosperity while ensuring health and social protection is a formidable policy challenge for 'labour sending' countries such as Sri Lanka. PMID- 24242227 TI - Editorial introduction. PMID- 24242228 TI - Harlequin Ichthyosis among the Navajo: Counseling issues. AB - Harlequin Ichthyosis is a rare, fatal congenital disorder of keratinization characterized by thickened, scale-like plaques of skin with a diamond configuration. Autosomal recessive inheritance has been established, and prenatal diagnosis for this disorder remains controversial. Five infants with this disorder were born among approximately 25,000 Navajo women who delivered in Gallup, New Mexico from 1970 to 1989. The incidence of 1 in 5000 among the Navajo in Gallup is high compared to previous reports in other populations. Two families with affected infants were seen in a genetics outreach clinic. Two important counseling issues were raised: (1) reluctance to discuss the possibility of recurrence for fear of affecting the outcome, and (2) feelings of guilt caused by cultural beliefs which attributed the birth defect to paternal behavior during pregnancy. Such issues are encountered in many traditional cultures, and they can be addressed by tailoring the timing and content of counseling. PMID- 24242230 TI - Abstracts of papers and posters presented at the third european meeting on psychosocial aspects of genetics. PMID- 24242229 TI - Medium-chain acyl CoA dehydrogenase deficiency: Its relationship to SIDS and the impact on genetic counseling. AB - Sudden infant death syndrome (SIDS) is defined as the sudden and unexpected death of an apparently healthy infant under 1 year of age. Routine autopsies often provide few clues as to the cause of death and rarely include a biochemical evaluation. Genetic counseling for SIDS can be difficult as recurrence risks vary depending on the age at death and the number of deaths which have occurred in the family. Biochemical disorders may account for up to 5% of SIDS. Of the metabolic disorders known to be involved in SIDS, the most commonly found is medium-chain acyl CoA dehydrogenase deficiency (MCAD). MCAD is an autosomal recessive disorder of fatty acid oxidation which accounts for up to 1% of SIDS. For some families, the addition of a postmortem biochemical investigation can identify an unsuspected metabolic disorder as the cause of death. Once the diagnosis is established, accurate genetic counseling can then be provided. Metabolic testing of the surviving siblings of victims of sudden death, and the subsequent identification of those due to MCAD can prevent the tragedy of recurrent SIDS in some families. In addition, screening the survivors of an acute life threatening event (ALTE) may also prevent a recurrence. PMID- 24242231 TI - Genetic library. PMID- 24242232 TI - Seasonal evaluation of bioaerosols from indoor air of residential apartments within the metropolitan area in South Korea. AB - The aims of the present study were to determine the levels of bioaerosols including airborne culturable bacteria (total suspended bacteria, Gram-positive bacteria, Staphylococcus, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria), fungi, endotoxin, and viruses (influenza A, influenza B, respiratory syncytial virus types A/B, parainfluenza virus types 1/2/3, metapnemovirus, and adenovirus) and their seasonal variations in indoor air of residential apartments. Of the total suspended bacteria cultured in an indoor environment, Staphylococcus was dominant and occupied 49.0 to 61.3% of indoor air. Among Staphylococcus, S. aureus were detected in 100% of households' indoor air ranging from 4 to 140 CFU/m(3), and 66% of households were positive for MRSA ranging from 2 to 80 CFU/m(3). Staphylococcus and S. aureus concentrations correlated with indoor temperature (adjusted beta: 0.4440 and 0.403, p < 0.0001). Among respiratory viruses, adenovirus was detected in 14 (14%) samples and influenza A virus was detected in 3 (3%) samples regarding the indoor air of apartments. Adenovirus concentrations were generally higher in winter (mean concentration was 2,106 copies/m(3)) than in spring (mean concentration was 173 copies/m(3)), with concentrations ranging between 12 and 560 copies/m(3). Also, a strong negative correlation between adenovirus concentrations and relative humidity in indoor air was observed (r = -0.808, p < 0.01). Furthermore, temperature also negatively correlated with adenovirus concentrations (r = -0.559, p < 0.05). PMID- 24242233 TI - Heavy metal (As, Cd, Hg, Pb, Cu, Zn, Se) concentrations in muscle and bone of four commercial fish caught in the central Adriatic Sea, Italy. AB - Heavy metal (As, Cd, Cu, Pb, Zn, Hg and Se) concentrations in the muscle and bone of four fish species (Mullus barbatus, Merluccius merluccius, Micromesistius poutassou, and Scomber scombrus) from the central Adriatic Sea were measured and the relationships between fish size (length and weight) and metal concentrations in the tissues were investigated. Samples were analyzed by inductively coupled plasma-atomic emission spectrophotometry with automatic dual viewing. In the muscle, results of linear regression analysis showed that, except for mercury, significant relationships between metal concentrations and fish size were negative. Only mercury levels were positively correlated with Atlantic mackerel size (p < 0.05). No significant variations of heavy metal concentrations were observed in muscles of the examined species, but a significant difference (p < 0.01) was found for As, Cd, Pb, and Se concentrations in bone. All the investigated metals showed higher values in the muscle than in bone, except for lead and zinc. Regarding cadmium, lead, and mercury maximum levels, set for the edible portion by European legislation, several samples exceeded these values, confirming the heavy metal presence in species caught near the Jabuka Pit. PMID- 24242234 TI - Prevalence and fimbrial genotype distribution of poultry Salmonella isolates in China (2006 to 2012). AB - In this study, a total of 323 Salmonella enterica strains were isolated from 3,566 rectal swab samples of 51 poultry farms in seven regions of 12 provinces of China between 2006 and 2012. The prevalences of Salmonella sp. carriage were 12.4% in geese (66 positive/533 samples), 10.4% in turkeys (32/309), 9.8% in chickens (167/1,706), 6.8% in ducks (41/601), and 4.1% in pigeons (17/417), respectively. These isolates belonged to 20 serovars, in which the most frequent serovars were S. enterica serovar Gallinarum biovar Pullorum (herein, S. Pullorum) (55 isolates, 17.0%), S. enterica serovar Typhimurium (50 isolates, 15.5%), and S. enterica serovar Enteritidis (39 isolates, 12.1%). Overall, S. Typhimurium was the most commonly detected serovar; among the individual species, S. Pullorum was most commonly isolated from chickens, S. Enteritidis was most common in ducks, S. Typhimurium was most common in geese and pigeons, and S. enterica serovar Saintpaul was most common in turkeys. PCR determination of 20 fimbrial genes demonstrated the presence of bcfD, csgA, fimA, stdB, and sthE genes and the absence of staA and stgA genes in these isolates, and other loci were variably distributed, with frequency values ranging from 11.8 to 99.1%. These 323 Salmonella isolates were subdivided into 41 different fimbrial genotypes, and of these isolate, 285 strains (88.2%) had 12 to 14 fimbrial genes. Our findings indicated that the Salmonella isolates from different poultry species were phenotypically and genetically diverse and that some fimbrial genes are more frequently associated with serovars or serogroups. PMID- 24242235 TI - pH-dependent activation of Streptomyces hygroscopicus transglutaminase mediated by intein. AB - Microbial transglutaminase (MTG) from Streptomyces is naturally secreted as a zymogen (pro-MTG), which is then activated by the removal of its N-terminal proregion by additional proteases. Inteins are protein-intervening sequences that catalyze protein splicing without cofactors. In this study, a pH-dependent Synechocystis sp. strain PCC6803 DnaB mini-intein (SDB) was introduced into pro MTG to simplify its activation process by controlling pH. The recombinant protein (pro-SDB-MTG) was obtained, and the activation process was determined to take 24 h at pH 7 in vitro. To investigate the effect of the first residue in MTG on the activity and the cleavage time, two variants, pro-SDB-MTG(D1S) and pro-SDB MTG(DeltaD1), were expressed, and the activation time was found to be 6 h and 30 h, respectively. The enzymatic property and secondary structure of the recombinant MTG and two variants were similar to those of the wild type, indicating that the insertion of mini-intein did not affect the function of MTG. This insignificant effect was further illustrated by molecular dynamics simulations. This study revealed a controllable and effective strategy to regulate the activation process of pro-MTG mediated by a mini-intein, and it may have great potential for industrial MTG production. PMID- 24242236 TI - GouR, a TetR family transcriptional regulator, coordinates the biosynthesis and export of gougerotin in Streptomyces graminearus. AB - Gougerotin is a peptidyl nucleoside antibiotic. It functions as a specific inhibitor of protein synthesis by binding ribosomal peptidyl transferase and exhibits a broad spectrum of biological activities. gouR, situated in the gougerotin biosynthetic gene cluster, encodes a TetR family transcriptional regulatory protein. Gene disruption and genetic complementation revealed that gouR plays an important role in the biosynthesis of gougerotin. Transcriptional analysis suggested that GouR represses the transcription of the gouL-to-gouB operon consisting of 11 structural genes and activates the transcription of the major facilitator superfamily (MFS) transporter gene (gouM). Electrophoresis mobility shift assays (EMSAs) and DNase I footprinting experiments showed that GouR has specific DNA-binding activity for the promoter regions of gouL, gouM, and gouR. Our data suggested that GouR modulates gougerotin production by coordinating its biosynthesis and export in Streptomyces graminearus. PMID- 24242237 TI - Bifidobacterium bifidum PRL2010 modulates the host innate immune response. AB - Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF-kappaB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. PMID- 24242239 TI - The fitness advantage of commercial wine yeasts in relation to the nitrogen concentration, temperature, and ethanol content under microvinification conditions. AB - The effect of the main environmental factors governing wine fermentation on the fitness of industrial yeast strains has barely received attention. In this study, we used the concept of fitness advantage to measure how increasing nitrogen concentrations (0 to 200 mg N/liter), ethanol (0 to 20%), and temperature (4 to 45 degrees C) affects competition among four commercial wine yeast strains (PDM, ARM, RVA, and TTA). We used a mathematical approach to model the hypothetical time needed for the control strain (PDM) to out-compete the other three strains in a theoretical mixed population. The theoretical values obtained were subsequently verified by competitive mixed fermentations in both synthetic and natural musts, which showed a good fit between the theoretical and experimental data. Specifically, the data show that the increase in nitrogen concentration and temperature values improved the fitness advantage of the PDM strain, whereas the presence of ethanol significantly reduced its competitiveness. However, the RVA strain proved to be the most competitive yeast for the three enological parameters assayed. The study of the fitness of these industrial strains is of paramount interest for the wine industry, which uses them as starters of their fermentations. Here, we propose a very simple method to model the fitness advantage, which allows the prediction of the competitiveness of one strain with respect to different abiotic factors. PMID- 24242238 TI - Competition for ammonia influences the structure of chemotrophic communities in geothermal springs. AB - Source waters sampled from Perpetual Spouter hot spring (pH 7.03, 86.4 degrees C), Yellowstone National Park, WY, have low concentrations of total ammonia, nitrite, and nitrate, suggesting nitrogen (N) limitation and/or tight coupling of N cycling processes. Dominant small-subunit rRNA sequences in Perpetual Spouter source sediments are closely affiliated with the ammonia-oxidizing archaeon "Candidatus Nitrosocaldus yellowstonii" and the putatively nitrogen-fixing (diazotrophic) bacterium Thermocrinis albus, respectively, suggesting that these populations may interact at the level of the bioavailable N pool, specifically, ammonia. This hypothesis was evaluated by using a combination of geochemical, physiological, and transcriptomic analyses of sediment microcosms. Amendment of microcosms with allylthiourea, an inhibitor of ammonia oxidation, decreased rates of acetylene reduction (a proxy for N2 fixation) and nitrite production (a proxy for ammonia oxidation) and decreased transcript levels of structural genes involved in both nitrogen fixation (nifH) and ammonia oxidation (amoA). In contrast, amendment of microcosms with ammonia stimulated nitrite production and increased amoA transcript levels while it suppressed rates of acetylene reduction and decreased nifH transcript levels. Sequencing of amplified nifH and amoA transcripts from native sediments, as well as microcosms, at 2 and 4 h postamendment, indicates that the dominant and responsive populations involved in ammonia oxidation and N2 fixation are closely affiliated with Ca. Nitrosocaldus yellowstonii and T. albus, respectively. Collectively, these results suggest that ammonia-oxidizing archaea, such as Ca. Nitrosocaldus yellowstonii, have an apparent affinity for ammonia that is higher than that of the diazotrophs present in this ecosystem. Depletion of the bioavailable N pool through the activity of ammonia-oxidizing archaea likely represents a strong selective pressure for the inclusion of organisms capable of nitrogen fixation in geothermal communities. These observations help to explain the strong pattern in the codistribution of ammonia-oxidizing archaea and diazotrophs in circumneutral-to-alkaline geothermal springs. PMID- 24242240 TI - Interaction of Aeromonas strains with lactic acid bacteria via Caco-2 cells. AB - The genus Aeromonas includes some species that have now been identified as human pathogens of significant medical importance. We investigated the ability of 13 selected Aeromonas strains belonging to nine species isolated from clinical cases (n = 5), environmental waters (n = 5), and fish (n = 3) to adhere to and translocate Caco-2 cells in the absence and presence of two lactic acid bacteria (LAB), i.e., Lactobacillus acidophilus and Bifidobacterium breve. Aeromonas isolates were also assessed for their cytotoxicity, the presence of virulence genes, and hemolysin production. Among the clinical isolates, one strain of Aeromonas veronii biovar veronii and two strains of Aeromonas hydrophila carried cytotoxin (act), heat-labile toxin (alt), hemolysin (hlyA), and aerolysin (aerA) genes, were cytotoxic to Vero cells, produced hemolysin, and showed higher adherence to Caco-2 cells. In contrast, this was seen in only one environmental strain, a strain of A. veronii biovar sobria. When Aeromonas strains were coinoculated with LAB onto Caco-2 cells, their level of adhesion was reduced. However, their rate of translocation in the presence of LAB increased and was significantly (P < 0.05) higher among fish strains. We suggest that either the interaction between Aeromonas and LAB strains could have a detrimental effect on the Caco-2 cells, allowing the Aeromonas to translocate more readily, or the presence of the LAB stimulated the Aeromonas strains to produce more toxins and/or increase their translocation rate. PMID- 24242241 TI - Oral bacterial communities in individuals with type 2 diabetes who live in southern Thailand. AB - Type 2 diabetes mellitus is increasingly common in Thailand and elsewhere. In the present investigation, the bacteriological composition of saliva and supragingival plaque in Thai diabetics with and without active dental caries and in nondiabetics was determined by differential culture and eubacterial DNA profiling. Potential associations between fasting blood sugar and glycosylated hemoglobin (biomarkers of current and historical glucose control, respectively) with decayed, missing, and filled teeth and with salivary Streptococcus and Lactobacillus counts were also investigated. The incidence of active dental caries was greater in the Thai diabetics than in nondiabetics, and the numbers of total streptococci and lactobacilli were significantly higher in supragingival plaque from diabetics than in nondiabetics. Lactobacillus counts in the saliva and supragingival plaque of diabetics with active caries were significantly higher than those in diabetics without active caries. Oral eubacterial DNA profiles of diabetic versus nondiabetic individuals and of diabetics with active caries versus those without active caries could not be readily differentiated through cluster analysis or multidimensional scaling. The elevated caries incidence in the Thai diabetics was positively associated with numbers of bacteria of the acidogenic/acid-tolerant genera Streptococcus and Lactobacillus. Lactobacillus bacterial numbers were further elevated in diabetics with active caries, although salivary eubacterial DNA profiles were not significantly altered. PMID- 24242242 TI - Lactobacillus helveticus MIMLh5-specific antibodies for detection of S-layer protein in Grana Padano protected-designation-of-origin cheese. AB - Single-chain variable-fragment antibodies (scFvs) have considerable potential in immunological detection and localization of bacterial surface structures. In this study, synthetic phage-displayed antibody libraries were used to select scFvs against immunologically active S-layer protein of Lactobacillus helveticus MIMLh5. After three rounds of panning, five relevant phage clones were obtained, of which four were specific for the S-layer protein of L. helveticus MIMLh5 and one was also capable of binding to the S-layer protein of L. helveticus ATCC 15009. All five anti-S-layer scFvs were expressed in Escherichia coli XL1-Blue, and their specificity profiles were characterized by Western blotting. The anti-S layer scFv PolyH4, with the highest specificity for the S-layer protein of L. helveticus MIMLh5, was used to detect the S-layer protein in Grana Padano protected-designation-of-origin (PDO) cheese extracts by Western blotting. These results showed promising applications of this monoclonal antibody for the detection of immunomodulatory S-layer protein in dairy (and dairy-based) foods. PMID- 24242243 TI - Uncovering a microbial enigma: isolation and characterization of the streamer generating, iron-oxidizing, acidophilic bacterium "Ferrovum myxofaciens". AB - A betaproteobacterium, shown by molecular techniques to have widespread global distribution in extremely acidic (pH 2 to 4) ferruginous mine waters and also to be a major component of "acid streamer" growths in mine-impacted water bodies, has proven to be recalcitrant to enrichment and isolation. A modified "overlay" solid medium was devised and used to isolate this bacterium from a number of mine water samples. The physiological and phylogenetic characteristics of a pure culture of an isolate from an abandoned copper mine ("Ferrovum myxofaciens" strain P3G) have been elucidated. "F. myxofaciens" is an extremely acidophilic, psychrotolerant obligate autotroph that appears to use only ferrous iron as an electron donor and oxygen as an electron acceptor. It appears to use the Calvin Benson-Bassham pathway to fix CO2 and is diazotrophic. It also produces copious amounts of extracellular polymeric materials that cause cells to attach to each other (and to form small streamer-like growth in vitro) and to different solid surfaces. "F. myxofaciens" can catalyze the oxidative dissolution of pyrite and, like many other acidophiles, is tolerant of many (cationic) transition metals. "F. myxofaciens" and related clone sequences form a monophyletic group within the Betaproteobacteria distantly related to classified orders, with genera of the family Nitrosomonadaceae (lithoautotrophic, ammonium-oxidizing neutrophiles) as the closest relatives. On the basis of the phylogenetic and phenotypic differences of "F. myxofaciens" and other Betaproteobacteria, a new family, "Ferrovaceae," and order, "Ferrovales," within the class Betaproteobacteria are proposed. "F. myxofaciens" is the first extreme acidophile to be described in the class Betaproteobacteria. PMID- 24242245 TI - Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities. AB - The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory activities. PMID- 24242244 TI - Analysis of the gull fecal microbial community reveals the dominance of Catellicoccus marimammalium in relation to culturable Enterococci. AB - Gulls are prevalent in beach environments and can be a major source of fecal contamination. Gulls have been shown to harbor a high abundance of fecal indicator bacteria (FIB), such as Escherichia coli and enterococci, which can be readily detected as part of routine beach monitoring. Despite the ubiquitous presence of gull fecal material in beach environments, the associated microbial community is relatively poorly characterized. We generated comprehensive microbial community profiles of gull fecal samples using Roche 454 and Illumina MiSeq platforms to investigate the composition and variability of the gull fecal microbial community and to measure the proportion of FIB. Enterococcaceae and Enterobacteriaceae were the two most abundant families in our gull samples. Sequence comparisons between short-read data and nearly full-length 16S rRNA gene clones generated from the same samples revealed Catellicoccus marimammalium as the most numerous taxon among all samples. The identification of bacteria from gull fecal pellets cultured on membrane-Enterococcus indoxyl-beta-D-glucoside (mEI) plates showed that the dominant sequences recovered in our sequence libraries did not represent organisms culturable on mEI. Based on 16S rRNA gene sequencing of gull fecal isolates cultured on mEI plates, 98.8% were identified as Enterococcus spp., 1.2% were identified as Streptococcus spp., and none were identified as C. marimammalium. Illumina deep sequencing indicated that gull fecal samples harbor significantly higher proportions of C. marimammalium 16S rRNA gene sequences (>50-fold) relative to typical mEI culturable Enterococcus spp. C. marimammalium therefore can be confidently utilized as a genetic marker to identify gull fecal pollution in the beach environment. PMID- 24242247 TI - Expression and characterization of CYP52 genes involved in the biosynthesis of sophorolipid and alkane metabolism from Starmerella bombicola. AB - Three cytochrome P450 monooxygenase CYP52 gene family members were isolated from the sophorolipid-producing yeast Starmerella bombicola (former Candida bombicola), namely, CYP52E3, CYP52M1, and CYP52N1, and their open reading frames were cloned into the pYES2 vector for expression in Saccharomyces cerevisiae. The functions of the recombinant proteins were analyzed with a variety of alkane and fatty acid substrates using microsome proteins or a whole-cell system. CYP52M1 was found to oxidize C16 to C20 fatty acids preferentially. It converted oleic acid (C18:1) more efficiently than stearic acid (C18:0) and linoleic acid (C18:2) and much more effectively than alpha-linolenic acid (C18:3). No products were detected when C10 to C12 fatty acids were used as the substrates. Moreover, CYP52M1 hydroxylated fatty acids at their omega- and omega-1 positions. CYP52N1 oxidized C14 to C20 saturated and unsaturated fatty acids and preferentially oxidized palmitic acid, oleic acid, and linoleic acid. It only catalyzed omega hydroxylation of fatty acids. Minor omega-hydroxylation activity against myristic acid, palmitic acid, palmitoleic acid, and oleic acid was shown for CYP52E3. Furthermore, the three P450s were coassayed with glucosyltransferase UGTA1. UGTA1 glycosylated all hydroxyl fatty acids generated by CYP52E3, CYP52M1, and CYP52N1. The transformation efficiency of fatty acids into glucolipids by CYP52M1/UGTA1 was much higher than those by CYP52N1/UGTA1 and CYP52E3/UGTA1. Taken together, CYP52M1 is demonstrated to be involved in the biosynthesis of sophorolipid, whereas CYP52E3 and CYP52N1 might be involved in alkane metabolism in S. bombicola but downstream of the initial oxidation steps. PMID- 24242246 TI - Quorum-sensing regulation of constitutive plantaricin by Lactobacillus plantarum strains under a model system for vegetables and fruits. AB - This study aimed at investigating the regulatory system of bacteriocin synthesis by Lactobacillus plantarum strains in vegetables and fruits in a model system. Sterile and neutralized cell-free supernatant (CFS) from L. plantarum strains grown in MRS broth showed in vitro antimicrobial activities toward various indicator strains. The highest activity was that of L. plantarum C2. The antimicrobial activity was further assayed on vegetable and fruit agar plates (solid conditions) and in juices (liquid conditions). A regulatory mechanism of bacteriocin synthesis via quorum sensing was hypothesized. The synthesis of antimicrobial compounds seemed to be constitutive under solid conditions of growth on vegetable and fruit agar plates. In contrast, it depended on the size of the inoculum when L. plantarum C2 was grown in carrot juice. Only the inoculum of ca. 9.0 log CFU ml(-1) produced detectable activity. The genes plnA, plnEF, plnG, and plnH were found in all L. plantarum strains. The genes plnJK and plnN were detected in only three or four strains. Reverse-phase high-performance liquid chromatography purification and mass spectrometry analysis revealed the presence of a mixture of eight peptides in the most active fraction of the CFS from L. plantarum C2. Active peptides were encrypted into bacteriocin precursors, such as plantaricins PlnJ/K and PlnH and PlnG, which are involved in the ABC transport system. A real-time PCR assay showed an increase in the expression of plnJK and plnG during growth of L. plantarum C2 in carrot juice. PMID- 24242249 TI - Aeromonas hydrophila and Aeromonas veronii predominate among potentially pathogenic ciprofloxacin- and tetracycline-resistant aeromonas isolates from Lake Erie. AB - Members of the genus Aeromonas are ubiquitous in nature and have increasingly been implicated in numerous diseases of humans and other animal taxa. Although some species of aeromonads are human pathogens, their presence, density, and relative abundance are rarely considered in assessing water quality. The objectives of this study were to identify Aeromonas species within Lake Erie, determine their antibiotic resistance patterns, and assess their potential pathogenicity. Aeromonas strains were isolated from Lake Erie water by use of Aeromonas selective agar with and without tetracycline and ciprofloxacin. All isolates were analyzed for hemolytic ability and cytotoxicity against human epithelial cells and were identified to the species level by using 16S rRNA gene restriction fragment length polymorphisms and phylogenetic analysis based on gyrB gene sequences. A molecular virulence profile was identified for each isolate, using multiplex PCR analysis of six virulence genes. We demonstrated that Aeromonas comprised 16% of all culturable bacteria from Lake Erie. Among 119 Aeromonas isolates, six species were identified, though only two species (Aeromonas hydrophila and A. veronii) predominated among tetracycline- and ciprofloxacin-resistant isolates. Additionally, both of these species demonstrated pathogenic phenotypes in vitro. Virulence gene profiles demonstrated a high prevalence of aerolysin and serine protease genes among A. hydrophila and A. veronii isolates, a genetic profile which corresponded with pathogenic phenotypes. Together, our findings demonstrate increased antibiotic resistance among potentially pathogenic strains of aeromonads, illustrating an emerging potential health concern. PMID- 24242250 TI - The secreted esterase of Propionibacterium freudenreichii has a major role in cheese lipolysis. AB - Free fatty acids are important flavor compounds in cheese. Propionibacterium freudenreichii is the main agent of their release through lipolysis in Swiss cheese. Our aim was to identify the esterase(s) involved in lipolysis by P. freudenreichii. We targeted two previously identified esterases: one secreted esterase, PF#279, and one putative cell wall-anchored esterase, PF#774. To evaluate their role in lipolysis, we constructed overexpression and knockout mutants of P. freudenreichii CIRM-BIA1(T) for each corresponding gene. The sequences of both genes were also compared in 21 wild-type strains. All strains were assessed for their lipolytic activity on milk fat. The lipolytic activity observed matched data previously reported in cheese, thus validating the relevance of the method used. The mutants overexpressing PF#279 or PF#774 released four times more fatty acids than the wild-type strain, demonstrating that both enzymes are lipolytic esterases. However, inactivation of the pf279 gene induced a 75% reduction in the lipolytic activity compared to that of the wild-type strain, whereas inactivation of the pf774 gene did not modify the phenotype. Two of the 21 wild-type strains tested did not display any detectable lipolytic activity. Interestingly, these two strains exhibited the same single nucleotide deletion at the beginning of the pf279 gene sequence, leading to a premature stop codon, whereas they harbored a pf774 gene highly similar to that of the other strains. Taken together, these results clearly demonstrate that PF#279 is the main lipolytic esterase in P. freudenreichii and a key agent of Swiss cheese lipolysis. PMID- 24242248 TI - Identification and environmental distribution of dcpA, which encodes the reductive dehalogenase catalyzing the dichloroelimination of 1,2-dichloropropane to propene in organohalide-respiring chloroflexi. AB - Dehalococcoides mccartyi strains KS and RC grow with 1,2-dichloropropane (1,2-D) as an electron acceptor in enrichment cultures derived from hydrocarbon contaminated and pristine river sediments, respectively. Transcription, expression, enzymatic, and PCR analyses implicated the reductive dehalogenase gene dcpA in 1,2-D dichloroelimination to propene and inorganic chloride. Quantitative real-time PCR (qPCR) analyses demonstrated a D. mccartyi cell increase during growth with 1,2-D and suggested that both D. mccartyi strains carried a single dcpA gene copy per genome. D. mccartyi strain RC and strain KS produced 1.8 * 10(7) +/- 0.1 * 10(7) and 1.4 * 10(7) +/- 0.5 * 10(7) cells per MUmol of propene formed, respectively. The dcpA gene was identified in 1,2-D-to propene-dechlorinating microcosms established with sediment samples collected from different geographical locations in Europe and North and South America. Clone library analysis revealed two distinct dcpA phylogenetic clusters, both of which were captured by the dcpA gene-targeted qPCR assay, suggesting that the qPCR assay is useful for site assessment and bioremediation monitoring at 1,2-D contaminated sites. PMID- 24242251 TI - Interspecies interactions determine the impact of the gut microbiota on nutrient allocation in Drosophila melanogaster. AB - The animal gut is perpetually exposed to microorganisms, and this microbiota affects development, nutrient allocation, and immune homeostasis. A major challenge is to understand the contribution of individual microbial species and interactions among species in shaping these microbe-dependent traits. Using the Drosophila melanogaster gut microbiota, we tested whether microbe-dependent performance and nutritional traits of Drosophila are functionally modular, i.e., whether the impact of each microbial taxon on host traits is independent of the presence of other microbial taxa. Gnotobiotic flies were constructed with one or a set of five of the Acetobacter and Lactobacillus species which dominate the gut microbiota of conventional flies (Drosophila with untreated microbiota). Axenic (microbiota-free) flies exhibited prolonged development time and elevated glucose and triglyceride contents. The low glucose content of conventional flies was recapitulated in gnotobiotic Drosophila flies colonized with any of the 5 bacterial taxa tested. In contrast, the development rates and triglyceride levels in monocolonized flies varied depending on the taxon present: Acetobacter species supported the largest reductions, while most Lactobacillus species had no effect. Only flies with both Acetobacter and Lactobacillus had triglyceride contents restored to the level in conventional flies. This could be attributed to two processes: Lactobacillus-mediated promotion of Acetobacter abundance in the fly and a significant negative correlation between fly triglyceride content and Acetobacter abundance. We conclude that the microbial basis of host traits varies in both specificity and modularity; microbe-mediated reduction in glucose is relatively nonspecific and modular, while triglyceride content is influenced by interactions among microbes. PMID- 24242252 TI - A moderately thermophilic mixed microbial culture for bioleaching of chalcopyrite concentrate at high pulp density. AB - Three kinds of samples (acid mine drainage, coal mine wastewater, and thermal spring) derived from different sites were collected in China. Thereafter, these samples were combined and then inoculated into a basal salts solution in which different substrates (ferrous sulfate, elemental sulfur, and chalcopyrite) served as energy sources. After that, the mixed cultures growing on different substrates were pooled equally, resulting in a final mixed culture. After being adapted to gradually increasing pulp densities of chalcopyrite concentrate by serial subculturing for more than 2 years, the final culture was able to efficiently leach the chalcopyrite at a pulp density of 20% (wt/vol). At that pulp density, the culture extracted 60.4% of copper from the chalcopyrite in 25 days. The bacterial and archaeal diversities during adaptation were analyzed by denaturing gradient gel electrophoresis and constructing clone libraries of the 16S rRNA gene. The results show that the culture consisted mainly of four species, including Leptospirillum ferriphilum, Acidithiobacillus caldus, Sulfobacillus acidophilus, and Ferroplasma thermophilum, before adapting to a pulp density of 4%. However, L. ferriphilum could not be detected when the pulp density was greater than 4%. Real-time quantitative PCR was employed to monitor the microbial dynamics during bioleaching at a pulp density of 20%. The results show that A. caldus was the predominant species in the initial stage, while S. acidophilus rather than A. caldus became the predominant species in the middle stage. F. thermophilum accounted for the greatest proportion in the final stage. PMID- 24242253 TI - UV light inactivation of human and plant pathogens in unfiltered surface irrigation water. AB - Fruit and vegetable growers continually battle plant diseases and food safety concerns. Surface water is commonly used in the production of fruits and vegetables and can harbor both human- and plant-pathogenic microorganisms that can contaminate crops when used for irrigation or other agricultural purposes. Treatment methods for surface water are currently limited, and there is a need for suitable treatment options. A liquid-processing unit that uses UV light for the decontamination of turbid juices was analyzed for its efficacy in the treatment of surface waters contaminated with bacterial or oomycete pathogens, i.e., Escherichia coli, Salmonella enterica, Listeria monocytogenes, Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato, and Phytophthora capsici. Five-strain cocktails of each pathogen, containing approximately 10(8) or 10(9) CFU/liter for bacteria or 10(4) or 10(5) zoospores/liter for Ph. capsici, were inoculated into aliquots of two turbid surface water irrigation sources and processed with the UV unit. Pathogens were enumerated before and after treatment. In general, as the turbidity of the water source increased, the effectiveness of the UV treatment decreased, but in all cases, 99.9% or higher inactivation was achieved. Log reductions ranged from 10.0 to 6.1 and from 5.0 to 4.2 for bacterial pathogens and Ph. capsici, respectively. PMID- 24242254 TI - New model for electron flow for sulfate reduction in Desulfovibrio alaskensis G20. AB - To understand the energy conversion activities of the anaerobic sulfate-reducing bacteria, it is necessary to identify the components involved in electron flow. The importance of the abundant type I tetraheme cytochrome c3 (TpIc3) as an electron carrier during sulfate respiration was questioned by the previous isolation of a null mutation in the gene encoding TpIc3, cycA, in Desulfovibrio alaskensis G20. Whereas respiratory growth of the CycA mutant with lactate and sulfate was little affected, growth with pyruvate and sulfate was significantly impaired. We have explored the phenotype of the CycA mutant through physiological tests and transcriptomic and proteomic analyses. Data reported here show that electrons from pyruvate oxidation do not reach adenylyl sulfate reductase, the enzyme catalyzing the first redox reaction during sulfate reduction, in the absence of either CycA or the type I cytochrome c3:menaquinone oxidoreductase transmembrane complex, QrcABCD. In contrast to the wild type, the CycA and QrcA mutants did not grow with H2 or formate and sulfate as the electron acceptor. Transcriptomic and proteomic analyses of the CycA mutant showed that transcripts and enzymes for the pathway from pyruvate to succinate were strongly decreased in the CycA mutant regardless of the growth mode. Neither the CycA nor the QrcA mutant grew on fumarate alone, consistent with the omics results and a redox regulation of gene expression. We conclude that TpIc3 and the Qrc complex are D. alaskensis components essential for the transfer of electrons released in the periplasm to reach the cytoplasmic adenylyl sulfate reductase and present a model that may explain the CycA phenotype through confurcation of electrons. PMID- 24242255 TI - From genus to phylum: large-subunit and internal transcribed spacer rRNA operon regions show similar classification accuracies influenced by database composition. AB - We compared the classification accuracy of two sections of the fungal internal transcribed spacer (ITS) region, individually and combined, and the 5' section (about 600 bp) of the large-subunit rRNA (LSU), using a naive Bayesian classifier and BLASTN. A hand-curated ITS-LSU training set of 1,091 sequences and a larger training set of 8,967 ITS region sequences were used. Of the factors evaluated, database composition and quality had the largest effect on classification accuracy, followed by fragment size and use of a bootstrap cutoff to improve classification confidence. The naive Bayesian classifier and BLASTN gave similar results at higher taxonomic levels, but the classifier was faster and more accurate at the genus level when a bootstrap cutoff was used. All of the ITS and LSU sections performed well (>97.7% accuracy) at higher taxonomic ranks from kingdom to family, and differences between them were small at the genus level (within 0.66 to 1.23%). When full-length sequence sections were used, the LSU outperformed the ITS1 and ITS2 fragments at the genus level, but the ITS1 and ITS2 showed higher accuracy when smaller fragment sizes of the same length and a 50% bootstrap cutoff were used. In a comparison using the larger ITS training set, ITS1 and ITS2 had very similar accuracy classification for fragments between 100 and 200 bp. Collectively, the results show that any of the ITS or LSU sections we tested provided comparable classification accuracy to the genus level and underscore the need for larger and more diverse classification training sets. PMID- 24242256 TI - Resisting and challenging stigma in Uganda: the role of support groups of people living with HIV. AB - INTRODUCTION: Global scale up of antiretroviral therapy is changing the context of HIV-related stigma. However, stigma remains an ongoing concern in many countries. Groups of people living with HIV can contribute to the reduction of stigma. However, the pathways through which they do so are not well understood. METHODS: This paper utilizes data from a qualitative study exploring the impact of networked groups of people living with HIV in Jinja and Mbale districts of Uganda. Participants were people living with HIV (n=40), members of their households (n=10) and their health service providers (n=15). Data were collected via interviews and focus group discussions in 2010, and analyzed inductively to extract key themes related to the approaches and outcomes of the groups' anti stigma activities. RESULTS: Study participants reported that HIV stigma in their communities had declined as a result of the collective activities of groups of people living with HIV. However, they believed that stigma remained an ongoing challenge. Gender, family relationships, social and economic factors emerged as important drivers of stigma. Challenging stigma collectively transcended individual experiences and united people living with HIV in a process of social renegotiation to achieve change. Groups of people living with HIV provided peer support and improved the confidence of their members, which ultimately reduced self-stigma and improved their ability to deal with external stigma when it was encountered. CONCLUSIONS: Antiretroviral therapy and group-based approaches in the delivery of HIV services are opening up new avenues for the collective participation of people living with HIV to challenge HIV stigma and act as agents of social change. Interventions for reducing HIV stigma should be expanded beyond those that aim to increase the resilience and coping mechanisms of individuals, to those that build the capacity of groups to collectively cope with and challenge HIV stigma. Such interventions should be gender sensitive and should respond to contextual social, economic and structural factors that drive stigma. PMID- 24242257 TI - Individual-level socioeconomic status and community-level inequality as determinants of stigma towards persons living with HIV who inject drugs in Thai Nguyen, Vietnam. AB - INTRODUCTION: HIV infection may be affected by multiple complex socioeconomic status (SES) factors, especially individual socioeconomic disadvantage and community-level inequality. At the same time, stigma towards HIV and marginalized groups has exacerbated persistent concentrated epidemics among key populations, such as persons who inject drugs (PWID) in Vietnam. Stigma researchers argue that stigma fundamentally depends on the existence of economic power differences in a community. In rapidly growing economies like Vietnam, the increasing gap in income and education levels, as well as an individual's absolute income and education, may create social conditions that facilitate stigma related to injecting drug use and HIV. METHODS: A cross-sectional baseline survey assessing different types of stigma and key socioeconomic characteristics was administered to 1674 PWID and 1349 community members living in physical proximity throughout the 32 communes in Thai Nguyen province, Vietnam. We created four stigma scales, including HIV-related and drug-related stigma reported by both PWID and community members. We then used ecologic Spearman's correlation, ordinary least-squares regression and multi-level generalized estimating equations to examine community level inequality associations, individual-level SES associations and multi-level SES associations with different types of stigma, respectively. RESULTS: There was little urban-rural difference in stigma among communes. Higher income inequality was marginally associated with drug-related stigma reported by community members (p=0.087), and higher education inequality was significantly associated with higher HIV-related stigma reported by both PWID and community members (p<0.05). For individuals, higher education was significantly associated with lower stigma (HIV and drug related) reported by both PWID and community members. Part-time employed PWID reported more experiences and perceptions of drug-related stigma, while conversely unemployed community members reported enacting lower drug related stigma. Multi-level analysis revealed that the relationship between education inequality and HIV-related stigma is superseded by the effect of individual-level education. CONCLUSIONS: The results of the study confirm that socioeconomic factors at both the individual level and community level affect different types of stigma in different ways. Attention should be paid to these differences when planning structural or educational interventions to reduce stigma, and additional research should investigate the mechanisms with which SES and inequality affect social relationships and, in turn, stigma. PMID- 24242260 TI - Testing the efficacy of an HIV stigma reduction intervention with medical students in Puerto Rico: the SPACES project. AB - INTRODUCTION: Stigma associated with HIV has been documented as a barrier for accessing quality health-related services. When the stigma manifests in the health care setting, people living with HIV receive substandard services or even be denied care altogether. Although the consequences of HIV stigma have been documented extensively, efforts to reduce these negative attitudes have been scarce. Interventions to reduce HIV stigma should be implemented as part of the formal training of future health care professionals. The interventions that have been tested with health care professionals and published have several limitations that must be surpassed (i.e. lack of comparison groups in research designs and longitudinal follow-up data). Furthermore, Latino health care professionals have been absent from these intervention efforts even though the epidemic has affected this population disproportionately. METHODS: In this article, we describe an intervention developed to reduce HIV stigma among medical students in Puerto Rico. A total of 507 medical students were randomly introduced into our intervention and control conditions. RESULTS: The results show statistically significant differences between the intervention and control groups; intervention group participants had lower HIV stigma levels than control participants after the intervention. In addition, differences in HIV stigma levels between the groups were sustained for a 12-month period. CONCLUSION: The results of our study demonstrate the efficacy of the modes of intervention developed by us and serve as a new training tool for future health care professionals with regard to stigma reduction. PMID- 24242258 TI - Impact of HIV-related stigma on treatment adherence: systematic review and meta synthesis. AB - INTRODUCTION: Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. METHODS: We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. RESULTS: Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants' ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's chi (2)=7.7; p=0.005). CONCLUSIONS: We found that HIV-related stigma compromised participants' abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence. PMID- 24242259 TI - Assessment of HIV-related stigma in a US faith-based HIV education and testing intervention. AB - INTRODUCTION: The African American church is a highly influential institution with the potential to greatly increase the reach of HIV prevention interventions and address HIV-related stigma in US African American communities. However, there are few studies on HIV-related stigma and African American church populations. This study explored HIV-related stigma among church and community members participating in an HIV education and testing intervention pilot study in African American churches, named Taking It to the Pews. METHODS: Four African American churches located in Kansas City, MO and KS, were randomized to either intervention or comparison groups. Churches assigned to the intervention group received religiously tailored HIV education, testing and compassion messages/activities (e.g. sermons, brochures/church bulletins, testimonials) via the Taking It to the Pews HIV Tool Kit. Comparison churches received non religiously tailored HIV information. HIV-related stigma was assessed with 543 church members and with community members served through church outreach services (e.g. food/clothing pantries, social services) in the four churches. Participants completed surveys at baseline, 6 months and 12 months to assess their HIV-related stigma beliefs, exposure to intervention components and satisfaction with the study. RESULTS: At baseline, HIV-related stigma beliefs were similar across experimental groups and were quite low. Mean HIV-related stigma scores were not significantly different between experimental groups at 6 months (p=0.92) or at 12 months (p=0.70). However, mean HIV-related stigma scores within both groups showed decreasing trends at six months, which approached significance. Analysis of previously studied HIV-related stigma factors (e.g. age, gender, income, HIV knowledge, religiosity) did not yield changes in the null findings. Intervention group participants were highly exposed to several intervention components (sermons, HIV resource tables, posters, brochures/church bulletins). Overall, participants were highly satisfied with the intervention pilot study. CONCLUSIONS: African American churches may be well positioned to increase the reach of HIV prevention interventions to church and community members and could serve an important role in addressing HIV-related stigma in their church communities. Future research is needed on measuring HIV-related stigma beliefs and on testing intensive, scalable, religiously tailored HIV interventions to impact HIV-related stigma in African American churches. PMID- 24242261 TI - Implementing a stigma reduction intervention in healthcare settings. AB - INTRODUCTION: Globally, HIV-related stigma is prevalent in healthcare settings and is a major barrier to HIV prevention and treatment adherence. Some intervention studies have showed encouraging outcomes, but a gap continues to exist between what is known and what is actually delivered in medical settings to reduce HIV-related stigma. METHODS: This article describes the process of implementing a stigma reduction intervention trial that involved 1760 service providers in 40 hospitals in China. Guided by Diffusion of Innovation theory, the intervention identified and trained about 15-20% providers as popular opinion leaders (POLs) to disseminate stigma reduction messages in each intervention hospital. The intervention also engaged governmental support in the provision of universal precaution supplies to all participating hospitals in the trial. The frequency of message diffusion and reception, perceived improvement in universal precaution practices and reduction in the level of stigma in hospitals were measured at 6- and 12-month follow-up assessments. RESULTS: Within the intervention hospitals, POL providers reported more frequent discussions with their co-workers regarding universal precaution principles, equal treatment of patients, provider-patient relationships and reducing HIV-related stigma. Service providers in the intervention hospitals reported more desirable intervention outcomes than providers in the control hospitals. Our evaluation revealed that the POL model is compatible with the target population, and that the unique intervention entry point of enhancing universal precaution and occupational safety was the key to improved acceptance by service providers. The involvement of health authorities in supporting occupational safety was an important element for sustainability. CONCLUSIONS: This report focuses on explaining the elements of our intervention rather than its outcomes. Lessons learned from the intervention implementation will enrich the development of future programs that integrate this or other intervention models into routine medical practice, with the aim of reducing HIV-related stigma and improving HIV testing, treatment and care in medical settings. PMID- 24242262 TI - Community-based interventions that work to reduce HIV stigma and discrimination: results of an evaluation study in Thailand. AB - INTRODUCTION: HIV stigma and discrimination are major issues affecting people living with HIV in their everyday lives. In Thailand, a project was implemented to address HIV stigma and discrimination within communities with four activities: (1) monthly banking days; (2) HIV campaigns; (3) information, education and communication (IEC) materials and (4) "Funfairs." This study evaluates the effect of project interventions on reducing community-level HIV stigma. METHODS: A repeated cross-sectional design was developed to measure changes in HIV knowledge and HIV-related stigma domains among community members exposed to the project. Two cross-sectional surveys were implemented at baseline (respondent n=560) and endline (respondent n=560). T-tests were employed to assess changes on three stigma domains: fear of HIV infection through daily activity, shame associated with having HIV and blame towards people with HIV. Baseline scales were confirmed at endline, and each scale was regressed on demographic characteristics, HIV knowledge and exposure to intervention activities. RESULTS: No differences were observed in respondent characteristics at baseline and endline. Significant changes were observed in HIV transmission knowledge, fear of HIV infection and shame associated with having HIV from baseline to endline. Respondents exposed to three specific activities (monthly campaign, Funfair and IEC materials) were less likely to exhibit stigma along the dimensions of fear (3.8 points lower on average compared to respondents exposed to none or only one intervention; 95% CI: -7.3 to -0.3) and shame (4.1 points lower; 95% CI: -7.7 to -0.6), net of demographic controls and baseline levels of stigma. Personally knowing someone with HIV was associated with low fear and shame, and females were less likely to possess attitudes of shame compared to males. CONCLUSIONS: The multivariate linear models suggest that a combination of three interventions was critical in shifting community-level stigma--monthly campaign, Funfair and IEC materials. This is especially important given Thailand's new national AIDS strategy to reduce HIV-related stigma and discrimination by half by 2016. Knowing which interventions to invest in for HIV stigma reduction is crucial for country-wide expansion and scale-up of intervention activities. PMID- 24242263 TI - Sexual stigma and discrimination as barriers to seeking appropriate healthcare among men who have sex with men in Swaziland. AB - INTRODUCTION: Same-sex practices and orientation are both stigmatized and criminalized in many countries across sub-Saharan Africa. This study aimed to assess the relationship of fear of seeking healthcare and disclosure of same-sex practices among a sample of men who have sex with men (MSM) in Swaziland with demographic, socio-economic and behavioural determinants. METHODS: Three hundred and twenty-three men who reported having had anal sex with a man in the past year were recruited using respondent-driven sampling and administered a structured survey instrument. Asymptotically unbiased estimates of prevalence of stigma and human rights abuses generated using the RDSII estimator are reported with bootstrapped confidence intervals (CIs). Weighted simple and multiple logistic regressions of fear of seeking healthcare and disclosure of same-sex practices to a healthcare provider with demographic, social and behavioural variables are reported. RESULTS: Stigma was common, including 61.7% (95% CI=54.0-69.0%) reporting fear of seeking healthcare, 44.1% (95% CI=36.2-51.3%) any enacted stigma and 73.9% (95% CI=67.7-80.1%) any perceived social stigma (family, friends). Ever disclosing sexual practices with other men to healthcare providers was low (25.6%, 95% CI=19.2-32.1%). In multiple logistic regression, fear of seeking healthcare was significantly associated with: having experienced legal discrimination as a result of sexual orientation or practice (aOR=1.9, 95% CI=1.1 3.4), having felt like you wanted to end your life (aOR=2.0, 95% CI=1.2-3.4), having been raped (aOR=11.0, 95% CI=1.4-84.4), finding it very difficult to insist on condom use when a male partner does not want to use a condom (aOR=2.1, 95% CI=1.0-4.1) and having a non-Swazi nationality at birth (aOR=0.18, 95% CI=0.05-0.68). In multiple logistic regression, disclosure of same-sex practices to a healthcare provider was significantly associated with: having completed secondary education or more (aOR=5.1, 95% CI=2.5-10.3), having used a condom with last casual male sexual partner (aOR=2.4, 95% CI=1.0-5.7) and having felt like you wanted to end your life (aOR=2.1, 95% CI=1.2-3.8). CONCLUSIONS: MSM in Swaziland report high levels of stigma and discrimination. The observed associations can inform structural interventions to increase healthcare seeking and disclosure of sexual practices to healthcare workers, facilitating enhanced behavioural and biomedical HIV-prevention approaches among MSM in Swaziland. PMID- 24242264 TI - Reducing shame in a game that predicts HIV risk reduction for young adult MSM: a randomized trial delivered nationally over the Web. AB - INTRODUCTION: Men who have sex with men (MSM) often face socially sanctioned disapproval of sexual deviance from the heterosexual "normal." Such sexual stigma can be internalized producing a painful affective state (i.e., shame). Although shame (e.g., addiction) can predict risk-taking (e.g., alcohol abuse), sexual shame's link to sexual risk-taking is unclear. Socially Optimized Learning in Virtual Environments (SOLVE) was designed to reduce MSM's sexual shame, but whether it does so, and if that reduction predicts HIV risk reduction, is unclear. To test if at baseline, MSM's reported past unprotected anal intercourse (UAI) is related to shame; MSM's exposure to SOLVE compared to a wait-list control (WLC) condition reduces MSM's shame; and shame-reduction mediates the link between WLC condition and UAI risk reduction. METHODS: HIV-negative, self identified African American, Latino or White MSM, aged 18-24 years, who had had UAI with a non-primary/casual partner in the past three months were recruited for a national online study. Eligible MSM were computer randomized to either WLC or a web-delivered SOLVE. Retained MSM completed baseline measures (e.g., UAI in the past three months; current level of shame) and, in the SOLVE group, viewed at least one level of the game. At the end of the first session, shame was measured again. MSM completed follow-up UAI measures three months later. All data from 921 retained MSM (WLC condition, 484; SOLVE condition, 437) were analyzed, with missing data multiply imputed. RESULTS: At baseline, MSM reporting more risky sexual behaviour reported more shame (r s=0.21; p<0.001). MSM in the SOLVE intervention reported more shame reduction (M=-0.08) than MSM in the control condition (M=0.07; t(919)=4.24; p<0.001). As predicted, the indirect effect was significant (point estimate -0.10, 95% bias-corrected CI [-0.01 to -0.23] such that participants in the SOLVE treatment condition reported greater reductions in shame, which in turn predicted reductions in risky sexual behaviour at follow-up. The direct effect, however, was not significant. CONCLUSIONS: SOLVE is the first intervention to: (1) significantly reduce shame for MSM; and (2) demonstrate that shame-reduction, due to an intervention, is predictive of risk (UAI) reduction over time. PMID- 24242265 TI - Prevalence and drivers of HIV stigma among health providers in urban India: implications for interventions. AB - INTRODUCTION: HIV stigma inflicts hardship and suffering on people living with HIV (PLHIV) and interferes with both prevention and treatment efforts. Health professionals are often named by PLHIV as an important source of stigma. This study was designed to examine rates and drivers of stigma and discrimination among doctors, nurses and ward staff in different urban healthcare settings in high HIV prevalence states in India. METHODS: This cross-sectional study enrolled 305 doctors, 369 nurses and 346 ward staff in both governmental and non governmental healthcare settings in Mumbai and Bengaluru, India. The approximately one-hour long interviews focused on knowledge related to HIV transmission, personal and professional experiences with PLHIV, instrumental and symbolic stigma, endorsement of coercive policies, and intent to discriminate in professional and personal situations that involve high and low risk of fluid exposure. RESULTS: High levels of stigma were reported by all groups. This included a willingness to prohibit female PLHIV from having children (55 to 80%), endorsement of mandatory testing for female sex workers (94 to 97%) and surgery patients (90 to 99%), and stating that people who acquired HIV through sex or drugs "got what they deserved" (50 to 83%). In addition, 89% of doctors, 88% of nurses and 73% of ward staff stated that they would discriminate against PLHIV in professional situations that involved high likelihood of fluid exposure, and 57% doctors, 40% nurses and 71% ward staff stated that they would do so in low-risk situations as well. Significant and modifiable drivers of stigma and discrimination included having less frequent contact with PLHIV, and a greater number of transmission misconceptions, blame, instrumental and symbolic stigma. Participants in all three groups reported high rates of endorsement of coercive measures and intent to discriminate against PLHIV. Stigma and discrimination were associated with multiple modifiable drivers, which are consistent with previous research, and which need to be targeted in future interventions. CONCLUSIONS: Stigma reduction intervention programmes targeting healthcare providers in urban India need to address fear of transmission, improve universal precaution skills, and involve PLHIV at all stages of the intervention to reduce symbolic stigma and ensure that relevant patient interaction skills are taught. PMID- 24242266 TI - A brief, standardized tool for measuring HIV-related stigma among health facility staff: results of field testing in China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis. AB - INTRODUCTION: Within healthcare settings, HIV-related stigma is a recognized barrier to access of HIV prevention and treatment services and yet, few efforts have been made to scale-up stigma reduction programs in service delivery. This is in part due to the lack of a brief, simple, standardized tool for measuring stigma among all levels of health facility staff that works across diverse HIV prevalence, language and healthcare settings. In response, an international consortium led by the Health Policy Project, has developed and field tested a stigma measurement tool for use with health facility staff. METHODS: Experts participated in a content-development workshop to review an item pool of existing measures, identify gaps and prioritize questions. The resulting questionnaire was field tested in six diverse sites (China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis). Respondents included clinical and non-clinical staff. Questionnaires were self- or interviewer-administered. Analysis of item performance across sites examined both psychometric properties and contextual issues. RESULTS: The key outcome of the process was a substantially reduced questionnaire. Eighteen core questions measure three programmatically actionable drivers of stigma within health facilities (worry about HIV transmission, attitudes towards people living with HIV (PLHIV), and health facility environment, including policies), and enacted stigma. The questionnaire also includes one short scale for attitudes towards PLHIV (5-item scale, alpha=0.78). CONCLUSIONS: Stigma-reduction programmes in healthcare facilities are urgently needed to improve the quality of care provided, uphold the human right to healthcare, increase access to health services, and maximize investments in HIV prevention and treatment. This brief, standardized tool will facilitate inclusion of stigma measurement in research studies and in routine facility data collection, allowing for the monitoring of stigma within healthcare facilities and evaluation of stigma-reduction programmes. There is potential for wide use of the tool either as a stand-alone survey or integrated within other studies of health facility staff. PMID- 24242267 TI - Access to justice: evaluating law, health and human rights programmes in Kenya. AB - INTRODUCTION: In Kenya, human rights violations have a marked impact on the health of people living with HIV. Integrating legal literacy and legal services into healthcare appears to be an effective strategy to empower vulnerable groups and address underlying determinants of health. METHODS: We carried out an evaluation to collect evidence about the impact of legal empowerment programmes on health and human rights. The evaluation focused on Open Society Foundation supported legal integration activities at four sites: the Academic Model of Providing Access to Healthcare (AMPATH) facility, where the Legal Aid Centre of Eldoret (LACE) operates, in Eldoret; Kenyatta National Hospital's Gender-based Violence Recovery Centre, which hosts the COVAW legal integration program; and Christian Health Association of Kenya (CHAK) facilities in Mombasa and Naivasha. In consultation with the organizations implementing the programs, we designed a conceptual logic model grounded in human rights principles, identified relevant indicators and then coded structure, process and outcome indicators for the rights-related principles they reflect. The evaluation included a resource assessment questionnaire, a review of program records and routine data, and semi structured interviews and focus group discussions with clients and service providers. Data were collected in May-August 2010 and April-June 2011. RESULTS: Clients showed a notable increase in practical knowledge and awareness about how to access legal aid and claim their rights, as well as an enhanced ability to communicate with healthcare providers and to improve their access to healthcare and justice. In turn, providers became more adept at identifying human rights violations and other legal difficulties, which enabled them to give clients basic information about their rights, refer them to legal aid and assist them in accessing needed support. Methodological challenges in evaluating such activities point to the need to strengthen rights-oriented evaluation methods. CONCLUSIONS: Legal empowerment programmes have the potential to promote accountability, reduce stigma and discrimination and contribute to altering unjust structures and systems. Given their apparent value as a health and human rights intervention, particularly for marginalized populations, further rigorous evaluations are called for to support the scale-up of such programmes. PMID- 24242270 TI - Foreword: Global action to reduce HIV stigma and discrimination. PMID- 24242269 TI - Editorial: Global action to reduce HIV stigma and discrimination. AB - There is no question that the stigma and discrimination associated with HIV and AIDS can be reduced through intervention. The inclusion of stigma and discrimination reduction as a critical component of achieving an AIDS-free generation in recent UNAIDS, UN and PEPFAR political initiatives is promising. Yet national governments need evidence on effective interventions at the individual, community and societal levels in order to strategically incorporate stigma and discrimination reduction into national AIDS plans. Currently, the heterogeneity of stigma and discrimination reduction approaches and measurement makes it challenging to compare and contrast evaluated interventions. Moving forward, it is critical for the research community to: (1) clearly link intervention activities to the domains of stigma to be shifted; (2) assess the stigma domains in a consistent manner; and (3) link stigma and discrimination reduction with HIV prevention, care and treatment outcomes (e.g., uptake, adherence and retention of ART). These steps would further advance the scientific evidence base of stigma and discrimination reduction and allow for the identification of effective interventions that could be scaled up by national governments. PMID- 24242268 TI - A systematic review of interventions to reduce HIV-related stigma and discrimination from 2002 to 2013: how far have we come? AB - INTRODUCTION: HIV-related stigma and discrimination continue to hamper efforts to prevent new infections and engage people in HIV treatment, care and support programmes. The identification of effective interventions to reduce stigma and discrimination that can be integrated into national responses is crucial to the success of the global AIDS response. METHODS: We conducted a systematic review of studies and reports that assessed the effectiveness of interventions to reduce HIV stigma and discrimination between 1 January 2002 and 1 March 2013. Databases searched for peer-reviewed articles included PubMed, Scopus, EBSCO Host -CINAHL Plus, Psycinfo, Ovid, Sociofile and Popline. Reports were obtained from the www.HIVAIDSClearinghouse.eu, USAID Development Experience Clearinghouse, UNESCO HIV and AIDS Education Clearinghouse, Google, WHO and UNAIDS. Ancestry searches for articles included in the systematic review were also conducted. Studies of any design that sought to reduce stigma as a primary or secondary objective and included pre- and post-intervention measures of stigma were included. RESULTS: Of 2368 peer-reviewed articles and reports identified, 48 were included in our review representing 14 different target populations in 28 countries. The majority of interventions utilized two or more strategies to reduce stigma and discrimination, and ten included structural or biomedical components. However, most interventions targeted a single socio-ecological level and a single domain of stigma. Outcome measures lacked uniformity and validity, making both interpretation and comparison of study results difficult. While the majority of studies were effective at reducing the aspects of stigma they measured, none assessed the influence of stigma or discrimination reduction on HIV-related health outcomes. CONCLUSIONS: Our review revealed considerable progress in the stigma-reduction field. However, critical challenges and gaps remain which are impeding the identification of effective stigma-reduction strategies that can be implemented by national governments on a larger scale. The development, validation, and consistent use of globally relevant scales of stigma and discrimination are a critical next step for advancing the field of research in this area. Studies comparing the effectiveness of different stigma-reduction strategies and studies assessing the influence of stigma reduction on key behavioural and biomedical outcomes are also needed to maximize biomedical prevention efforts. PMID- 24242272 TI - Endothermic ion molecule reactions. AB - Endothermic ion-molecule reactions in a tandem mass spectrometer have been used for a number of years for determining thermodynamic quantities, such as heats of formation and proton affinities, for gaseous ions. Recently, the reactive, endothermic collision has been exploited as an analytical technique for the structural analysis of peptides and other biomolecules. The technique is based upon the endothermic transfer of protons associated with amide bonds to ammonia. This reaction proceeds via a long-lived collision complex. When additional beam energy is supplied, other dissociation channels are opened up, leading to the production of sequence ions for the mass-selected, protonated analyte that are normally observed in high energy collision-induced dissociation spectra. The advantage, however, is that such spectra can be produced at very low beam energies. In this article, the rationale for developing this scheme, and its roots in previous ion-molecule studies, are explored. PMID- 24242271 TI - Multiple time scale complexity analysis of resting state FMRI. AB - The present study explored multi-scale entropy (MSE) analysis to investigate the entropy of resting state fMRI signals across multiple time scales. MSE analysis was developed to distinguish random noise from complex signals since the entropy of the former decreases with longer time scales while the latter signal maintains its entropy due to a "self-resemblance" across time scales. A long resting state BOLD fMRI (rs-fMRI) scan with 1000 data points was performed on five healthy young volunteers to investigate the spatial and temporal characteristics of entropy across multiple time scales. A shorter rs-fMRI scan with 240 data points was performed on a cohort of subjects consisting of healthy young (age 23 +/- 2 years, n = 8) and aged volunteers (age 66 +/- 3 years, n = 8) to investigate the effect of healthy aging on the entropy of rs-fMRI. The results showed that MSE of gray matter, rather than white matter, resembles closely that of f (-1) noise over multiple time scales. By filtering out high frequency random fluctuations, MSE analysis is able to reveal enhanced contrast in entropy between gray and white matter, as well as between age groups at longer time scales. Our data support the use of MSE analysis as a validation metric for quantifying the complexity of rs-fMRI signals. PMID- 24242273 TI - High resolution on a quadrupole ion trap mass spectrometer. AB - By using a modified ion trap mass spectrometer, resolution in excess of 30,000 (FWHM) at m I z 502 is demonstrated. The method of increasing resolution in the ion trap mass spectrometer operated in the mass-selective instability mode depends on decreasing the rate of scanning the primary radio frequency amplitude as well as using resonance ejection at the appropriate frequency and amplitude. A theoretical basis for the method is introduced. PMID- 24242274 TI - An electrospray ion source for magnetic sector mass spectrometers. AB - Electro spray mass spectra of carbonic anhydrase (MW ~ 29000) and ovalbumin (MW ~ 45000) were obtained on a double focusing magnetic secter mass spectrometer by using a single stage of mechanical pumping in the interface between atmospheric pressure and high vacuum. Full scan spectra of lysozyme were recorded on 15 fmoles consumed. In addition, accurate mass measurement was demonstrated for peptides and proteins, and resolution in excess of 10,000 (m /?m, 10% valley) was observed. These results clearly show that high performance magnetic sector mass spectrometers can be advantageously interfaced to an atmospheric pressure electrospray ion source. PMID- 24242275 TI - Characterization of the reactive and dissociative behavior of transition metal oxide cluster ions in the gas phase. AB - The reactive and dissociative behavior of molybdenum and tungsten oxide cluster ions has been studied in the gas phase using a triple quadrupole mass spectrometer. Cluster ions (MO3) n (-) were formed via a simple thermal desorption/electron capture negative ionization method, and their structures were characterized by collision-activated dissociation (CAD). Typically, the clusters fragment by losses of neutral (MO3) units. Reactions of the oxide cluster ions with ethylene oxide, cyclohexene oxide, ethylene sulfide cyclohexene sulfide, 2,3 butanedione, and 2,4-pentanedione were examined, and product ions were characterized by CAD. The clusters react with ethylene oxide by addition of ethylene oxide or net addition of oxygen, whereas the clusters react with ethylene sulfide via net addition of one or two sulfur atoms. Reactions of the clusters with the diones result in addition of one or two dione units, in some cases with dehydration. PMID- 24242276 TI - Ion-Molecule reactions in methylamine and dimethylamine and trimethylamine systems. AB - Fourier transform ion cyclotron resonance mass spectrometry has been used to measure the reaction rates for ions derived from methylamine with dimethylamine or trimethylamine. The use of the selective ion ejection technique greatly simplifies the elucidation of the ion-molecule reaction channels. The rate constants for proton transfer from protonated metwlamine, CH3NH 3 (+) (m/z 32), to dimethylamine and trimethylamine are 16.1 +/- 1.6 * 10(-10) and 9.3 +/- 0.9 * 10(-10) cm(3) molec(-1)s(-1), respectively. The rate constants for charge transfer from methylamine molecular ion, CH3NH 2 (+) (m/z 31), to dimethylamine and trimethylamine are 9.3 +/- 1.8 x 10(-10) and 15.0 +/- 5 * 10(-10) cm(3)molec( 1)s(-1), respectively. PMID- 24242277 TI - Monitor for displaying real-time images of low energy ion beams. AB - Analytical Chemistry Division. Oak Ridge National Laboratory. Oak Ridge, Tennessee, USA A monitor that provides real-time images of low energy (< 50 eV) ion beams has been designed, constructed, and tested. The cross-sectional image of the beam at the entrance aperture of the monitor is magnified by a factor of 6.5 and displayed on a CRT, following current amplification by using a dual microchannel plate assembly. The monitor provides unambiguous information regarding the cross section of any low energy ion beam. Anplication in the design and testing of quadrupole-based mass spectrometers is emphasized. PMID- 24242278 TI - Detection mass bias in atmospheric pressure ionization mass spectrometry. AB - A previously uncharacterized source of detection mass bias is shown to be associated with atmospheric pressure ionization mass spectrometry (APIMS), and is attributed to a mass dependence in the sampling of ions from the supersonic free jet expansion of gas emerging from the ion source. The halide ions Cl (-), Br(-), and I(-) are shown to be transported from the ion source aperture to a quadrupole mass filter with efficiencies that increase linearly with increasing mass of the ion. While the polyatomic anions SF 6 (-) and C7F 14 (-) are detected with even greater efficiencies than would be expected for monatomic anions of the same mass, this additional sensitivity to the polyatomic anions is thought to be related to ion loss processes occurring within the ion source. The experimental conditions under which these mass bias effects can be minimized or enhanced in APIMS are described. PMID- 24242279 TI - Determination of plutonium 240/239 ratios in Lake Ontario sediments. AB - A thermal ionization mass spectrometric procedure was developed for determination of 240/239 ratios in subpicogram quantities of plutonium (Pu), and was applied to Pu extracted from Lake Ontario sediment. The detection limit was ~ 4 fg of Pu and the precision of 240/239 ratio measurement was ~ 7% in the 0.07-0.42 pg range. Results of sediment analyses at various depths showed in all cases 240/239 ratios near the mean global fallout value of 0.176 +/- 0.014. The lack of variability of the ratios with depth negated the use of Pu, present in excess in the near surface samples due to leakage from a nearby reprocessing plant, as a geochronological meter. The 240/239 ratio of the leakage Pu appeared to be very similar to that of fallout Pu. PMID- 24242280 TI - Pyridine-Containing schiff base derivatives for the struxtural determination of long-chain aldehydes by gas chromatography combined with mass spectrometry. AB - Long-chain aldehydes, encountered as insect pheromones, were converted into Schiff bases with 3-aminopyridine, 3-(aminomethyl)pyridine, or 2-aminopyrimidine to provide derivatives suitable for revealing the alkyl chain structure by mass spectrometry. The two pyridine-containing derivatives were satisfactory in initiating a radical-induced cleavage. of the chain to give a series of fragment ions, the masses and relative abundance of which revealed the chain structure. The derivatives were applied to aldehydes having straight, branched (iso and anteiso), and unsaturated (delta-7, delta-9, delta-ll, and delta-13) structures; these all gave the fragmentation patterns that have been seen earlier for similar pyridine-containing derivatives of fatty acids (picolinyl esters) and alcohols (nicotinates).Of the two derivatives, those from 3-aminopyridine gave slightly simpler spectra. Derivatives formed from 2-aminopyrimidine were less satisfactory in revealing chain structure. PMID- 24242281 TI - Selective detection of sulfur-containing compounds by gas chromatography/chemical reaction interface mass spectrometry. AB - Addition of a reactant gas to a low pressure microwave-induced plasma creates a reaction interface in which complex molecules are converted into small polyatomic neutral species. For a given reactant gas the array of these small molecules reflect s the elemental composition of the original analyte. In this study HCI has been found highly effective as a reactant gas for selective detection of sulfur-eontaining compounds using capillary gas chromatography/ chernical reaction interface mass spectrometry. Detection limits as low as 30 pg of a sulfur-containing compound and a dynamic range of two orders of magnitude were achieved. PMID- 24242282 TI - Isomer differentiation in 7, 12-dimethylbenz[a]anthracene-pyridine adducts by fast atom bombardment tandem mass spectrometry. AB - Three isomeric 7,12-dL-nethylbenz[alpha]anthracene-pyridine adduct salts, namely.. the 5-N-pyridinium-7,12-dimethylbenz[alpha]anthracene perchlorate, the 7 N-pyridiniummethylene-12methylbenz[ alpha]anthracene picrate, and the 7-methyl-12 N-pyridiniummethylenebenz[ alpha]anthracene picrate, were studied by fast atom bombardment tandem mass spectrometry using high energy collisional-activated dissociation (CAD). The CAD mass spectra of the molecular cations and the (M - pyridine)(+) ions allow one to distinguish positional isomers on the basis of daughter ion peak height ratios. The differences in the CAD mass spectra of the (M - pyridine)(+) ions are probably due in part to formation of isomer-specific fused-ring tropyliumions. PMID- 24242283 TI - Erratum to: A study of the gas-phase reaction between protonated acetaldehyde and reaction between protonated acetaldehyde and methanol. PMID- 24242284 TI - Ontogeny of consummatory successive negative contrast in rats. AB - Consummatory successive negative contrast (cSNC) occurs when organisms repeatedly exposed to a high-magnitude reward are suddenly given a low-magnitude reward. This results in a significant reduction in the consumption of the devalued reinforcer, at a level even below that of a group which had been always exposed to the low-magnitude reinforcer. A scarcity of animal studies assessed the expression of this phenomenon during early development. Three experiments assessed age of cSNC onset in preweanling rats. Percent body weight gained (%BWG) and taste reactions associated with reinforcement devaluation were measured. A reduction in %BWG and a significant increase in emission of aversive hedonic behaviors, indicative of cSNC, occurred on postnatal day 18 (PD 18; Experiments 1 and 2), but not on PD 14 or PD 17 (Experiments 3a and 3b). The neurobiological mechanisms underlying these effects and theoretical implications are discussed. PMID- 24242285 TI - Cosolvents induced unfolding and aggregation of keyhole limpet hemocyanin. AB - The objective of this study was to examine the effects of 2,2,2 trifluoroethanol (TFE) and acetonitrile (ACN) on the stability, behavior, and structural characteristics of giant multimeric protein Keyhole Limpet hemocyanin (KLH) by combining the circular dichroism (CD) and fluorescence measurements of KLH solution. In concentration range 20-50% (v/v) TFE, protein at pH 7.4 shows visible aggregation while no aggregation was observed in the entire concentration range of TFE at molten globule (MG) state (pH 2.8) and resulted in stable alpha helix. Our result shows that in the presence of 80% (v/v) and 40% (v/v) TFE, at native (pH 7.4) and MG state (pH 2.8) occurred in a highly helical state referred to as TFE denatured state I and II, respectively. However, in case of ACN, aggregation starts above 40% (v/v) for pH 7.4 and at 80% (v/v) for acid-induced MG (pH 2.8) state, which was dominated by beta-sheet structure and referred to as ACN denatured state III and IV. An important object of our investigation is to get more detail study of efficiency of cosolvents in inducing structural changes in KLH. The dependence of scattering intensity and the R h on alcohol concentrations was investigated at 25 degrees C. PMID- 24242286 TI - Association of genetic variants of MTHFR, ENPP1, and ADIPOQ with myocardial infarction in Egyptian patients. AB - The study aimed to investigate the association between MTHFR C677T, ENPP1 K121Q, and ADIPOQ 45 T/G gene polymorphisms and incidence of myocardial infarction (MI) in Egyptian patients. The study included 60 unrelated patients suffering from their first MI and 60 unrelated controls. Patients were recruited from Kasr-El Eini hospital, Cairo University. The previously mentioned polymorphisms were determined in all participants by PCR-RFLP. There was no significant difference in the distribution of genotypes and alleles of MTHFR C677T between groups. In contrast, significant difference was found in the distributions of genotypes and alleles of ENPP1 K121Q and ADIPOQ 45 T/G between MI patients and controls (P = 0.01, P = 0.004, P = 0.009, P = 0.001, respectively). Univariate analysis revealed that 121Q ENPP1 and 45 G ADIPOQ alleles were associated with the increased risk of MI (OR = 3; 95 % CI = 1.45-6.2; P = 0.004 and OR = 5.8; 95 % CI = 1.92-17.54; P = 0.001, respectively). The mutant homozygous genotypes of MTHFR, ENPP1, and ADIPOQ were more prevalent in diabetic hypertensive MI patients than it was among non-diabetic normotensive MI patients. Regarding the coagulation profile, INR (P = 0.009) and PC % (P = 0.022) were significantly different among the three genotypes of MTHFR C677T. The 677 T, 121 Q, and 45G variants were associated with MI in Egyptian patients; however, more studies are needed to determine the possible protective effect for these polymorphisms in our population. PMID- 24242287 TI - Novel hypoglycemic injury mechanism: N-methyl-D-aspartate receptor-mediated white matter damage. AB - OBJECTIVE: Hypoglycemia is a common adverse event and can injure central nervous system (CNS) white matter (WM). We determined whether glutamate receptors were involved in hypoglycemic WM injury. METHODS: Mouse optic nerves (MON), CNS WM tracts, were maintained at 37 degrees C with oxygenated artificial cerebrospinal fluid (ACSF) containing 10mM glucose. Aglycemia was produced by switching to 0 glucose ACSF. Supramaximal compound action potentials (CAPs) were elicited using suction electrodes, and axon function was quantified as the area under the CAP. Amino acid release was measured using high-performance liquid chromatography. Extracellular lactate concentration ([lactate(-)]o) was measured using an enzyme electrode. RESULTS: About 50% of MON axons were injured after 60 minutes of aglycemia (90% after 90 minutes); injury extent was not affected by animal age. Blockade of N-methyl-D-aspartate (NMDA)-type glutamate receptors improved recovery after 90 minutes of aglycemia by 250%. Aglycemic injury was increased by reducing [Mg(2+)]o or increasing [glycine]o , and decreased by lowering pHo , expected results for NMDA receptor-mediated injury. pHo increased during aglycemia due to a drop in [lactate(-)]o. Aglycemic injury was dramatically reduced in the absence of [Ca(2+)]o. Extracellular aspartate, a selective NMDA receptor agonist, increased during aglycemia ([glutamate]o fell). INTERPRETATION: Aglycemia injured WM by a unique excitotoxic mechanism involving NMDA receptors (located primarily on oligodendrocytes). During WM aglycemia, the selective NMDA agonist aspartate is released, probably from astrocytes. Injury is mediated by Ca(2+) influx through aspartate-activated NMDA receptors made permeable by an accompanying alkaline shift in pHo caused by a fall in [lactate(-)]o. These insights have important clinical implications. PMID- 24242289 TI - Surgical innovation as sui generis surgical research. AB - Successful innovative 'leaps' in surgical technique have the potential to contribute exponentially to surgical advancement, and thereby to improved health outcomes for patients. Such innovative leaps often occur relatively spontaneously, without substantial forethought, planning, or preparation. This feature of surgical innovation raises special challenges for ensuring sufficient evaluation and regulatory oversight of new interventions that have not been the subject of controlled investigatory exploration and review. It is this feature in particular that makes early-stage surgical innovation especially resistant to classification as 'research', with all of the attendant methodological and ethical obligations--of planning, regulation, monitoring, reporting, and publication--associated with such a classification. This paper proposes conceptual and ethical grounds for a restricted definition according to which innovation in surgical technique is classified as a form of sui generis surgical 'research', where the explicit goal of adopting such a definition is to bring about needed improvements in knowledge transfer and thereby benefit current and future patients. PMID- 24242288 TI - Ecological correlates of depression and self-esteem in rural youth. AB - The current study examines individual-, social-, and school-level characteristics influencing symptoms of depression and self-esteem among a large sample (N = 4,321) of U.S. youth living in two rural counties in the South. Survey data for this sample of middle-school students (Grade 6 to Grade 8) were part of the Rural Adaptation Project. Data were analyzed using ordered logistic regression. Results show that being female, having a low income, and having negative relationships with parents and peers are risk factors that increase the probability of reporting high levels of depressive symptoms and low levels of self-esteem. In contrast, supportive relationships with parents and peers, high religious orientation, ethnic identity, and school satisfaction increased the probability of reporting low levels of depressive symptoms and high levels of self-esteem. There were few school-level characteristics associated with levels of depressive symptoms and self-esteem. Implications are discussed. PMID- 24242290 TI - DNA aggregation and cleavage in CGE induced by high electric field in aqueous solution accompanying electrokinetic sample injection. AB - The phenomenon of peak area decrease due to high injection voltage (Vinj , e.g. 10-30 kV, 200-600 V/cm in the 50 cm capillary) was found in the analysis of very dilute DNA fragments (<0.2 mg/L) by using high-sensitive electrokinetic supercharging-CGE. The possibility of DNA cleavage in aqueous solution was suggested, in addition to the aggregation phenomenon that is already known. The analysis of intentionally voltage-affected fragments (at 200 V/cm) also showed decreased peak areas depending on the time of the voltage being applied. Computer simulation suggested that a high electric field (a few kV/cm or more) could be generated partly between the electrode and the capillary end during electrokinetic injection (EKI) process. After thorough experimental verification, it was found that the factors affecting the damage during EKI were the magnitude of electric field, the distance between tips of electrode and capillary (De/c ), sample concentration and traveling time during EKI in sample vials. Furthermore, these factors are correlating with each other. A low conductivity of diluted sample would cause a high electric field (over a few hundred volts per centimeter), while the longer De/c results in a longer traveling time during EKI, which may cause a larger degree of damage (aggregation and cleavage) on the DNA fragments. As an important practical implication of this study, when the dilute DNA fragments (sub mg/L) are to be analyzed by CGE using EKI, injection voltage should be kept as low as possible. PMID- 24242291 TI - Apoptotic cell death and altered calcium homeostasis caused by frataxin depletion in dorsal root ganglia neurons can be prevented by BH4 domain of Bcl-xL protein. AB - Friedreich ataxia (FRDA) is a neurodegenerative disease characterized by a decreased expression of the mitochondrial protein frataxin. Major neurological symptoms of the disease are due to degeneration of dorsal root ganglion (DRG) sensory neurons. In this study we have explored the neurodegenerative events occurring by frataxin depletion on primary cultures of neurons obtained from rat DRGs. Reduction of 80% of frataxin levels in these cells was achieved by transduction with lentivirus containing shRNA silencing sequences. Frataxin depletion caused mitochondrial membrane potential decrease, neurite degeneration and apoptotic cell death. A marked increase of free intracellular Ca(2+) levels and alteration in Ca(2+)-mediated signaling pathways was also observed, thus suggesting that altered calcium homeostasis can play a pivotal role in neurodegeneration caused by frataxin deficiency. These deleterious effects were reverted by the addition of a cell-penetrant TAT peptide coupled to the BH4, the anti-apoptotic domain of Bcl-x(L). Treatment of cultured frataxin-depleted neurons with TAT-BH4 was able to restore the free intracellular Ca(2+) levels and protect the neurons from degeneration. These observations open the possibility of new therapies of FRDA based on modulating the Ca(2+) signaling and prevent apoptotic process to protect DRG neurons from neurodegeneration. PMID- 24242292 TI - Clinicopathological and prognostic value of S100A4 expression in gastric cancer: a meta-analysis. AB - PURPOSES: For several years S100A4 has been implicated in tumor progression and prognosis. However, the prognostic value of S100A4 overexpression in patients with gastric cancer remains unknown. Therefore, we performed a meta-analysis to assess the relationship between S100A4 overexpression and clinical outcome of gastric cancer. METHODS AND RESULTS: Candidate studies were searched from PubMed, Embase, Cochrane Library, and ISI Web of Science. We included studies that evaluated the prognostic value of S100A4 expression in gastric cancer patients with regard to survival and a series of clinicopathological parameters. The pooled hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the effects. Ten studies, all from Asia, were included in the meta-analysis. The pooled analysis showed that S100A4 overexpression was significantly associated with worse overall survival (OS) (HR=1.86, 95% CI: 1.45 2.38, p<0.00001) without heterogeneity in the data (I2=43.6%, p=0.131). Furthermore, our results showed that S100A4 overexpression was significantly correlated with some clinicopathological parameters such as tumor grade, stage, metastasis, invasion, and relapse. CONCLUSIONS: The results of our meta-analysis indicate that S100A4 overexpression correlates with more adverse clinical features and a poor prognosis of gastric cancer patients in Asia, thus suggesting that S100A4 could be a useful marker to evaluate progression and prognosis of Asian gastric cancer patients. More studies from Western countries with a larger number of tumors and standardized methods are required before significant conclusions can be drawn. PMID- 24242293 TI - A standardized staining protocol for L1CAM on formalin-fixed, paraffin-embedded tissues using automated platforms. AB - The L1 cell adhesion molecule (L1CAM) is overexpressed in many human cancers and can serve as a biomarker for prognosis in most of these cancers (including type I endometrial carcinomas). Here we provide an optimized immunohistochemical staining procedure for a widely used automated platform (VENTANATM), which has recourse to commercially available primary antibody and detection reagents. In parallel, we optimized the staining on a semi-automated BioGenix (i6000) ?immunostainer. These protocols yield good stainings and should represent the basis for a reliable and standardized immunohistochemical detection of L1CAM in a variety of malignancies in different laboratories. PMID- 24242294 TI - A PNA-mediated clamping PCR for routine detection of KRAS mutations in colorectal carcinoma. AB - The detection of somatic mutations in a tumor represents a valuable tool for tumor characterization and provides the clinicians with information for setting up the most appropriate therapy. KRAS mutations in codons 12 and 13 are important biomarkers routinely analyzed in the clinic for the management of anti-EGFR treatment in colorectal carcinoma (CRC). Here we report a sensitive and inexpensive assay for KRAS mutations based on a PNA-mediated PCR clamping. The assay displays very high sensitivity (0.7%) and specificity (96.7%) when compared to traditional sequencing (SS) and pyrosequencing (PS), two of the most commonly and routinely used methods employed today by diagnostic laboratories. Furthermore, the PNA assay requires only basic and low-cost laboratory equipment, in contrast with all the most recent PCR-based technologies, which are highly sensitive but also much more expensive. Finally, despite the PNA assay does not allow for the definition of specific mutations, it is the cheapest and easiest screening method to firstly stratify wild-type and mutated patients, information that is strictly necessary to clinicians for the management of CRC and anti-EGFR treatment. PMID- 24242295 TI - Annexin A1 in malignant tumors: current opinions and controversies. AB - Annexin A1 is a 37 kDa calcium and phospholipid-binding protein that participates in several biological processes, such as inflammatory reactions, modulation of cell proliferation, regulation of cell death signaling, apoptosis, and, most importantly, tumor formation and development. Although annexin A1 has been implicated in the biology of various tumors, the findings are highly controversial and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which annexin A1 participates in carcinogenesis and tumor progression is rather unclear. In the current study, we review the important biological functions of annexin A1 in different tumors. This work indicates that annexin A1 is a possible target for novel therapeutic intervention and that it is a potential biomarker for tumor diagnosis and screening. PMID- 24242296 TI - Large molecule specific assay operation: recommendation for best practices and harmonization from the global bioanalysis consortium harmonization team. AB - The L2 Global Harmonization Team on large molecule specific assay operation for protein bioanalysis in support of pharmacokinetics focused on the following topics: setting up a balanced validation design, specificity testing, selectivity testing, dilutional linearity, hook effect, parallelism, and testing of robustness and ruggedness. The team additionally considered the impact of lipemia, hemolysis, and the presence of endogenous analyte on selectivity assessments as well as the occurrence of hook effect in study samples when no hook effect had been observed during pre-study validation. PMID- 24242297 TI - Behavioral and electrophysiological response of cabbage seed weevils (Ceutorhynchus assimilis) to conspecific odor. AB - The responses ofCeutorhynchus assimilis Payk. (Coleoptera, Curculionidae) to the odor of overwintered and new generation weevils were studied using an olfactometer, choice tests in a laboratory cage, field tests using sticky traps baited with live weevils, and by electroantennograms (EAG's). Unmated male weevils and, to a lesser extent, female weevils of the overwintered generation were attracted to the odor of live unmated over-wintered female weevils. New generation weevils exhibited no behavioral response to conspecific odor. Male and female weevils of the overwintered generation exhibited positive EAGs to hexane extracts of overwintered female weevils, whereas EAGs of new-generation weevils of either sex were unresponsive to these extracts. This suggests that the unmated female weevils from the overwintered generation produce a volatile chemical or chemicals that attracts unmated male and female weevils. The new generation of female weevils does not produce this attractive chemical before overwintering, and male and female weevils of this generation can not detect the chemical(s) via their antennal chemoreceptors until they have undergone their overwintering period. PMID- 24242298 TI - Leaf surface extracts ofSolanum berthaultii hawkes deter colorado potato beetle feeding. AB - Leaf rinses ofS. berthaultii PI 473334 with methylene chloride were deterrent to feeding by the Colorado potato beetle when applied toS. tuberosum tuber and leaf disks. When the leaf rinse was separated into its nonvolatile and volatile fractions and applied to tuber disks, the nonvolatile fraction was highly deterrent, while the volatile fraction reduced consumption, but not significantly compared to the controls. A hexane leaf rinse was not deterrent to feeding, while an acetone rinse was approximately twofold more deterrent than the methylene chloride rinse when applied to leaf disks. Three cycles of bioassay-guided, reversed-phase open-column fractionation of an acetone leaf rinse yielded a relatively polar fraction with low deterrent activity, and two nonpolar fractions exhibiting higher specific activity. Reversed-phase preparative HPLC of these fractions yielded seven active fractions among the 10 assayed. Subsequent analytical HPLC indicated that two fractions each contained a single UV-absorbing compound, while another represented a mixture of at least four compounds. The remaining fractions were composed of complex mixtures of possibly ionic or polymeric compounds that were poorly resolved by HPLC. PMID- 24242299 TI - Allelopathic potential in bilberry-spruce forests: Influence of phenolic compounds on spruce seedlings. AB - Regeneration failure ofPicea abies in a subalpine bilberry-spruce forest was studied in relation to phenolic compounds, their occurrence and toxicity. Germination bioassays with natural leachates of bilberry (Vaccinium myrtillus) and spruce showed negative effects on root elongation of spruce seedlings. Growth bioassays on litter and humus demonstrated inhibitory effects of these organic layers.p-Hydroxyacetophenone, a spruce-specific metabolite, was isolated in spruce throughfall (10(-6) M), in water extracts of litter (between 1 and 8 ug/g dry wt) and organic layer (less than 1 ug/g dry wt) in addition to tannins and several common phenolic acids. Potential relationships between vegetation cover and phenolic pattern of the soil are discussed, since organic layers under bilberry heath exhibited higher amounts of phenolic acids and tannins than those under spruce.p-Hydroxyacetophenone and caffeic acid reduced, even at 5 * 10(-5) M, spruce seedling growth, especially root development, with additive effects for these two monomers. Autotoxicity involving spruce trees and allelopathy of understory species, mediated byp-hydroxy-acetophenone and other phenolic compounds, including tannins, deserves further attention in regeneration studies. PMID- 24242300 TI - Relative activities of glucosinolates as oviposition stimulants forPieris rapae andP. napi oleracea. AB - The relative activities of 10 glucosinolates in stimulating oviposition byP. rapae andP. napi oleracea were compared under the same conditions. When tested at the same concentration, the structurally different glucosinolates stimulated both butterfly species to widely varying degrees. In most cases,P. rapae was more sensitive to aromatic and indole glucosinolates than to aliphatic representatives. This species responded even less to alkyl thio and sulfinyl glucosinolates. However,P. napi oleracea responded strongly to these aliphatic and sulfur-containing members of the group, and the relative activities of aromatic and aliphatic glucosinolates did not show a clear pattern for this species.P. napi oleracea was much more sensitive to low concentrations of sinigrin than wasP. rapae. The threshold concentration for response ofP. napi oleracea to sinigrin was 10(-8) M, which was 100 times lower than forP. rapae, butP. rapae was more sensitive thanP. napi oleracea to changes in glucosinolate concentrations. For bothPieris species, an optimal concentration was reached, above which the response remained constant or tended to decrease. PMID- 24242301 TI - Cardenolides as oviposition deterrents to twoPieris species: Structure-activity relationships. AB - Oviposition responses ofPieris rapae andP. napi oleracea to 18 cardenolides were compared under the same conditions. Effects of different concentrations of selected cardenolides were also tested. Most of the compounds were deterrent to oviposition by both insects, but to significantly different degrees.P. rapae were strongly deterred by K-strophanthoside, K-strophanthin-beta, cymarin, convallatoxin, oleandrin, erysimoside, erychroside, and gitoxigenin. The most deterrent compounds forP. napi oleracea were erychroside, cymarin, erysimoside, convallatoxin, and K-strophanthoside. Strophanthidin-based glycosides were more deterrent than digitoxigenin-based ones, and the number and type of sugar substitutions can have profound effects on activity. Both similarities and contrasts were found in responses ofP. rapae andP. napi oleracea to these cardenolides. Cymarin was equally deterrent to bothPieris species at all concentrations tested. However, when compared withP. rapae, P. napi oleracea was less sensitive to most of the cardenolides.P. napi oleracea was insensitive to K strophanthin-beta and oleandrin at 0.5 * 10(-4) M, which were highly deterrent toP. rapae. PMID- 24242302 TI - Attraction of reproductive honey bee swarms to artificial nests by Nasonov pheromone. AB - A crossover experimental design was established to test the attractancy of Nasonov pheromone to reproductive swarms of honey bees. Nineteen swarms were attracted to artificial nest cavities containing a slow-release blend of the Nasonov components citral, geraniol, and nerolic + geranic acids, and only four swarms were attracted to pheromone-free artificial nests. The results indicate that Nasonov pheromone plays a key role in the attraction of honey bee swarms to nest cavities. PMID- 24242303 TI - Biocatalytic synthesis of (S)-2-tridecanyl acetate and (S)-2-pentadecanyl acetate, aggregation pheromone components ofDrosophila mulleri andD. busckii, by enantioselective hydrolysis with lipase. AB - The two chiral pheromone acetates, (S)-2-tridecanyl acetate and (S)-2 pentadecanyl acetate, were synthesized with an enantiomeric excess (e.e.) of almost 100% byPseudomonas cepacia lipase-catalyzed hydrolysis of their corresponding racemic acetates in an acetone-water solvent system. PMID- 24242304 TI - Oxime ether analogs of sex pheromone components of turnip moth (Agrotis segetum Schiffermuller). AB - Oxime ether analogs of sex pheromone components of the turnip moth (Agrotis segetum Schiff.) were synthesized by the acidolytic opening of cyclic enol ethers withO-alkyl hydroxylamine hydrochlorides. The compounds varying in chain lengths and in the position of the C=N double bond were studied by electrophysiological single sensillum recordings (electrosen-sillography: ESG). The ESG data indicate in general reduced receptor interaction of all analogs investigated in comparison with natural pheromone components of the turnip moth. The data also show that the grade of decrease of receptor interaction depends on specific structural changes within the molecule. The results demonstrate high complementary pheromone receptor relationships, predominantly depending on the position of the unsaturated group in the chain, whereas analogs with other structural changes are still recognized as a pheromone-like compound by the receptor. PMID- 24242305 TI - Composition of larval secretion ofChrysomela lapponica (Coleoptera, Chrysomelidae) and its dependence on host plant. AB - The defensive secretion ofChrysomela lapponica larvae, which is produced by nine pairs of exocrine dorsal glands, has been chemically analyzed. TheC. lapponica larvae were kept in the laboratory on leaves of either birch (Betula pendula), alder (Alnus glutinosa), or willow (Salix fragilis). Larvae developed normally on birch and willow, whereas those on alder died within a few days. GC-MS analyses of the secretion of larvae on birch and willow revealed that the composition of this secretion differs distinctly from the known ones of several otherChrysomela species feeding exclusively on Salicaceae. In the exocrine secretion of larvae on birch, 69 compounds were identified, which included the main components isobutyric acid, 2-methylbutyric acid, and esters of the two. Several of the esters have not been reported previously from nature. The alcoholic components of the esters may be hydrolysis products ofBetula glycosides. Most components of the secretion of larvae feeding on birch were also found in the secretion of larvae feeding on willow. In addition, major amounts of benzoic acid and salicylalcohol were present in the secretion of the larvae feeding on willow.C. lapponica obviously acquires salicylalcohol by hydrolysis of salicin from willow leaves. However, in contrast to otherChrysomela species,C. lapponica larvae oxidize only traces of salicylalcohol to salicylaldehyde. The repellent activity of single authentic compounds of the secretion of larvae feeding on birch and willow, respectively, was tested in laboratory bioassays with ants (Myrmica sabuleti). Biosynthetic pathways to some identified compounds are suggested and discussed under evolutionary and functional aspects. PMID- 24242306 TI - Attractant pheromone for nearctic stink bug,Euschistus obscurus (Heteroptera: Pentatomidae): Insight into a neotropical relative. AB - Volatiles fromEuschistus obscurus males were found to be attractive to conspecific females in bioassays. A new type of olfactometer assembled from commercially available glassware was used to bioassay aeration extracts of the Nearctic stink bug,E. obscurus. Fractionated extracts suggest that pheromonal activity is associated with late-eluting, male-specific compounds. Research onE. obscurus offered a means to indirectly study the pheromone of the Neotropical pest species,E. heros, without importing this soybean pest into the United States. PMID- 24242307 TI - Identification of male-specific volatiles from nearctic and neotropical stink bugs (Heteroptera: Pentatomidae). AB - Males of the Central American stink bug species,Euschistus obscurus, produce an attractant pheromone composed of a blend of compounds characteristic of North AmericanEuschistus spp. and the South American soybean pest,E. heros. The range ofE. obscurus extends into the southern United States, the species is easy to rear, and males produce an exceptionally large quantity of pheromone (>0.5ug/day/male). These factors madeE. obscurus useful for characterizing the novel pheromone components ofE. heros without importing this pest species into the United States.Euschistus obscurus males produce methyl (2E,4Z)-decadienoate (61 %) in abundance, which is characteristic of North American species, and methyl 2,6,10-trimethyltridecanoate (27%), the main male-specific ester ofE. heros. The chirality ofEuschistus spp. methyl-branched esters, and field activity of synthetic formulations, remain to be determined. PMID- 24242308 TI - Responses by amphisbaenianBlanus cinereus to chemicals from prey or potentially harmful ant species. AB - We tested the ability of amphisbaenians (Blanus cinereus) to discriminate between odors of ant species selected as prey (Pheidole pallidula) and odors of potentially harmful ant species (Messor barbarus) that are avoided. Tongue-flick rate to swabs impregnated with ant odors, cologne, or deionized water differed among treatments, showing that amphisbaenians were able to discriminate ant species odors. Amphisbaenians showed an aggressive response and bit applicators bearing the odor of harmful ants, while the odor of prey ants did not elicit bites to swabs. The possible evolutionary advantage of identifying and avoiding harmful ants is discussed in relation to the fossoriality of amphisbaenians. PMID- 24242309 TI - Cuticular hydrocarbons ofAedes hendersoni cockerell andA. triseriatus (SAY). AB - Field-caught adult male and femaleAedes hendersoni are difficult to distinguish from the sibling speciesA. triseriatus. We found that mosquitoes from the same sex of the sibling species can not be readily separated either by unique cuticular hydrocarbon components or by differences in percent composition of those components. Multivariate analysis of the cuticular hydrocarbon data does not provide good separation. Cuticular hydrocarbons were identified using gas chromatography electron-impact mass spectrometry and gas chromatography chemical ionization mass spectrometry. Flame-ionization capillary gas chromatography was used for quantitative analysis of individual mosquitoes. Sixty-four hydrocarbons with chain lengths from C16 to greater than C46 were common to both species. Identified hydrocarbon components weren-alkanes, monomethylalkanes, dimethylalkanes, trimethylalkanes, and alkenes. PMID- 24242310 TI - Effects of organic solvents on use of tarbush by sheep. AB - Tarbush (Flourensia cernua DC) is a native perennial shrub prevalent in many parts of the Chihuahuan Desert. Ruminants have exhibited limited use of tarbush leaves and new leaders as a forage during the summer growing season. Efforts to increase use of tarbush by lambs through spraying with various organic solvents were unsuccessful, probably because of the highly variable response. However, complete immersion of tarbush in organic solvents (acetone and ethanol) increased (P<0.01) tarbush use by ram lambs when compared to unaltered tarbush. Data suggest that removal of secondary compounds from the leaf surface of tarbush using organic solvents enhanced acceptability of tarbush to sheep. PMID- 24242311 TI - Purification and preliminary characterization of a frog-derived proteinaceous chemoattractant eliciting prey attack by checkered garter snakes (Thamnophis marcianus). AB - A potent proteinaceous chemoattractant, eliciting prey attack by checkered garter snakes (Thamnophis marcianus) was isolated from aqueous washes of the common frogRana temporaria and purified by preparative continuous-elution electrophoresis. The biological activity of the frog crude extract or of the purified chemoattractive protein, measured by a snake bioassay, was unaffected by freezing, lyophilization, or dialysis but was lost after proteolytic digestion. The purified chemoattractant is glycosylated, has an apparent molecular mass of 24 kDa, estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE), and a pI of 4.8. It gave one spot in two-dimensional electrophoresis. The bioassay showed that this protein is highly attractive to snakes. The lowest concentration yielding positive responses in the snake bioassay was approximately 25 ug/ml. These results suggest that a water-soluble Mr 24 kDa glycoprotein molecule produced by the common frog may be a vomeronasal stimulus used by checkered garter snakes for prey recognition. PMID- 24242312 TI - A new bioassay for testing plant extracts and pure compounds using red flour beetleTribolium castaneum Herbst. AB - We designed a new bioassay to test plant extract activity against stored product pests. Plant compounds were added to feed disks composed of wheat flour and yeast and fed to the red flour bettle (Tribolium castaneum). By measuring insect mass, disk mass, and insect mortality over time it was possible to calculate a phagodepression index, an antifeedant index, the amount of treatment chemical ingested by the beetles, the mortality rate, and the efficiency of conversion of ingested food. The assay was performed for 60 hr to allow for possible habituation effects and to discriminate between phagodeterrency and physiological stress caused by treatments. alpha- and beta-Pinene, eugenol, kaurenic acid, sparteine, essential oils ofMinthostachis mollis andMelaleuca quinquenervia, and extracts ofSapindus saponaria were tested. Using this assay we detected the presence of both phagodepressant and phagostimulant compounds inS. saponaria extracts, and we quantified the pronounced effects of sparteine onT. castaneum. PMID- 24242313 TI - Effect of cultivation on allelopathic interference success of the weed,Pluchea lanceolata. AB - Pluchea lanceolata, a perennial noxious weed, is rapidly spreading into cultivated fields in semiarid regions of India. The objective of the present study was to evaluate the effect of cultivation on the interference success ofPluchea lanceolata by comparing chemical characteristics of the weed and its associated topsoil and subsoil in cultivated and uncultivated habitats. Weed plants from both cultivated and uncultivated habitats were analyzed for four biotic characteristics. Leaves were analyzed for nine chemical characteristics. Soils (topsoil and subsoil) were analyzed for 13 chemical characteristics. Nutrient concentrations of the weed and its associated soils, both in cultivated and uncultivated habitats, showed that plant response with reference to nutrient uptake was inversely related to that of soils. Thus, the weed does not create nutrient stress. With cultivation, leaf area and Cu and Na contents increased, while leaf ash, leaf weight, and Mg and Ca decreased. In the topsoil and subsoil, however, concentrations of total carbonates, total phenolics, and Ca increased with cultivation, while organic carbon, phosphate, and K decreased. High phenolic content of the cultivated fields could be explained due to leaching of water soluble compounds from the plant parts either through natural leaching or through various agricultural practices such as ploughing and irrigation. We concluded that water-soluble phenolics, leached from the weed into the soil, increased with cultivation. PMID- 24242314 TI - Direct and mediated effects onBactrocera oleae (Gmelin) (Diptera; Tephritidae) of natural polyphenols and some of related synthetic compounds: Structure-activity relationships. AB - Among the main polyphenols occurring in olive oil vegetation waters (VW), catechol showed the most deterrent action on the oviposition ofBactrocera oleae (Gmelin); 4-methylcatechol was less active, whereas hydroxytyrosol and tyrosol were inactive. In contrast, synthetico-quinone was found to be stimulant at 7.5 * 10(-2) M. Two other synthetic derivatives of catechol, diacetylcatechol and guaiacol, were also deterrent, suggesting these compounds undergo a biochemical transformation into catechol by means of the bacterial symbionts ofB. oleae. VW and their phenolic extracts showed deterrence only when highly concentrated, while natural olive juice was strongly deterrent. Experiments carried out to evaluate the effect of olive juice and catechol on the fecundity ofB. oleae showed that they strongly reduce this function. Moreover, the possible utilization of VW and their bioactive polyphenols in protection of olives againstBatrocera oleae is discussed. PMID- 24242315 TI - Detection of hypogeous fungi by Tasmanian bettong (Bettongia gaimardi: Marsupialia; Macropodoidea). AB - The ability of Tasmanian bettongs (Bettongia gaimardi) to locate hypogeous fungi (their main diet) was tested in a controlled laboratory situation. Bettongs dug directly over buried fungi significantly more often than they did over buried glass marbles or over disturbed soil. This ability was not enhanced as they gained experience. Bettongs dug more often over buried filter paper onto which fungus extract was absorbed than over control papers, and showed no discrimination between the outer and inner layers of the fungi. They preferred the odor of whole fungi to individual volatile compounds. They showed no reaction to the odor of the steroid ergosterol. PMID- 24242316 TI - Alarm pheromone system of leaf-footed bugLeptoglossus zonatus (Heteroptera: Coreidae). AB - The alarm pheromone system ofLeptoglossus zonatus (Dallas) adults was shown to be composed of hexyl acetate, hexanol, hexanal, and hexanoic acid. Single components tested in the field elicited dispersive behavior of over 70% of adults. 2-(E) Hexenal, found in the secretion of nymphs, but not in the exudates of adults, was also active against adults. In addition, first-instar nymphs responded to the four components of the alarm pheromone of adults as well as to 2-(E)-hexenal, a component of their own alarm pheromone system. Adults and nymphs possess different alarm pheromone systems, which are not specific to their own life stage. That hemipteran alarm pheromone systems are not species-specific was supported by the fact that both adult and nymphL. zonatus responded to butanoic acid, an alarm pheromone of Alydidae, which was not found in this Coreidae species. PMID- 24242319 TI - Genetic library. PMID- 24242318 TI - A survey of reimbursement for cystic fibrosis carrier testing. AB - To assess the current status of reimbursement for cystic fibrosis (CF) carrier testing, we surveyed individuals tested in the Mid-Atlantic region. Results show that CF testing was covered by insurance in part or in full for greater than 50% of respondents. The test was nearly always covered when performed during pregnancy because of a positive family history, but it was also covered for more than 50% of pregnant respondents with a negative family history. There were no significant differences in coverage by type of insurance. Many respondents needed to supply additional information about the testing to their insurance company before a coverage decision could be made. Before population-based CF screening programs are initiated, more data are needed on insurance reimbursement for testing, especially when performed pre-conceptually. PMID- 24242317 TI - Promoting remyelination in multiple sclerosis-recent advances. AB - We review the current state of knowledge of remyelination in multiple sclerosis (MS), concentrating on advances in the understanding of the pathology and the regenerative response, and we summarise progress on the development of new therapies to enhance remyelination aimed at reducing progressive accumulation of disability in MS. We discuss key target pathways identified in experimental models, as although most identified targets have not yet progressed to the stage of being tested in human clinical trials, they may provide treatment strategies for demyelinating diseases in the future. Finally, we discuss some of the problems associated with testing this class of drugs, where they might fit into the therapeutic arsenal and the gaps in our knowledge. PMID- 24242320 TI - Another perspective on genetic risk assessment for cancer. PMID- 24242321 TI - Introductory statement. PMID- 24242322 TI - A multidisciplinary approach to the prevention, evaluation, and management of work disability. AB - Occupational musculoskeletal disorders represent a major challenge to the injured worker, his or her family, the various health care, health and safety, and human resource professionals that work in this area as well as employers and the workers' compensation system. The epidemiology of the occupational musculoskeletal disorders and work disability indicate the problem is growing. Given the multiple factors that contribute to work disability and the complexity in the return to work process, the need to address the varied factors that contribute to work disability has become increasingly clear. Following a review of the magnitude of the problem, a conceptual framework that considers the multivariate nature of work disability is proposed as a heuristic for research and practice. Such an integrated approach argues for a broader consideration of work disability from a biomedical, biomechanical, and psychosocial framework. Last, this paper summarizes efforts to date in the areas of prevention, evaluation, and rehabilitation. The paper suggests that a number of factors have converged over the past 5-10 years that point to the need for a new approach to the problem of work disability, one that truly attempts to integrate the diverse groups and approaches of the past and seeks to develop new knowledge and strategies. It is expected that the Journal of Occupational Rehabilitation will facilitate such an integration. PMID- 24242323 TI - The reliability and validity of two new tests of maximum lifting capacity. AB - This study investigated the test-retest reliability and validity of the isokinetic and gravity/inertia modes of the Lido Lift (TM) and the Progressive Lifting Capacity II test (PLC II). Maximum lifting capacity tests were performed in the isokinetic and gravity/inertia modes on the Lido Lift and with the PLC II with 29 healthy male subjects. Pearson product-moment correlations were calculated to determine the test-retest reliabilities and to compare PLC II test values with isokinetic and gravity/inertia test values. The correlations for the isokinetic, gravity inertia, and the PLC II werer=.90, .82, and .91, respectively. The correlations between the isokinetic and gravity/inertia tests and the PLC II werer=.64 and .74 during the test andr=.72 and .81 during the retest. The results of this study support the reliability of both Lido Lift (TM) tests and of the PLC II, and the validity of the isokinetic and gravity/inertia tests when compared to the PLC II. PMID- 24242324 TI - Occupational health consultation as a systematic approach to managing work related musculoskeletal injuries. AB - An intricate balance of health care and administrative decision-making is necessary to ensure the accurate confirmation of an employee's disability and appropriate accommodation of his/her work limitations. In this article, an occupational health consult process is presented describing the interplay between the health care team, the disabled employee's supervisor, and human resource specialists-each having a categorical interest in the status of the employee. The occupational health nurse plays a central role in the administrative coordination of this interaction which requires effective yet careful communication between members of the health care team and the employee's supervisor. He/she should work closely with the disability specialist to reach common objectives. When conducted properly, occupational health consultation facilitates early and successful return to work for many employees who have incurred physical disabilities while employed. The significance of occupational health consultation is evident in light of current legislation that places greater expectations on employers to make reasonable accommodations for employees with disabilities. PMID- 24242325 TI - Symptom Magnification Syndrome Structured Interview: Rationale and procedure. AB - The identification of Symptom Magnification Syndrome is based in part on data collected during a clinical interview. The Symptom Magnification Syndrome Structured Interview (SMSSI) has been developed to provide structure to this data collection procedure. The SMSSI provides a standardized platform on which quantification of subjective reports can be based. The SMSSI addresses 14 issues that have previously been identified as related to the presence of symptom magnification syndrome. PMID- 24242327 TI - Physical therapy and occupational rehabilitation. AB - Occupational rehabilitation, while acknowledged as a multidisciplinary field, is only as effective as contributions of its individual disciplines. Physical therapy has been and is continuing to be an integral part of both the clinical and scientific portions of the team. Inherent in the physical therapy profession are three educational components which makes it a particularly suitable addition: movement science, pathology, and functional analysis. Physical therapists are active in each of the primary areas of occupational rehabilitation: musculoskeletal treatment, injury prevention education, functional capacity evaluation, restorative exercise, work hardening, ergonomics, and pre-work screening. Future challenges encompass increased skill in ergonomics, effectiveness in the return-to-work process, and in the scientific study of physical therapy techniques and their effectiveness. PMID- 24242326 TI - Posttraumatic reflex sympathetic dystrophy: Mechanisms and medical management. AB - Reflex sympathetic dystrophy (RSD) refers to a symptom complex of posttraumatic pain associated with a wide and varying spectrum of vasomotor and neurologic changes. The diagnosis of reflex sympathetic dystrophy is made almost entirely on clinical grounds, and is often confirmed by observation of the results of diagnostic local anesthetic nerve blocks. Laboratory and radiographic investigations are useful adjuncts to diagnosis. The key to successful management is early recognition, as delays in treatment are associated with worse outcome. A multimodal approach to treatment is recommended that may include nerve blocks, rehabilitation, and pharmacologic and behavioral pain management. The role of other modalities including surgery and electrical stimulation remains controversial. PMID- 24242328 TI - Isokinetic strength testing in monitoring progress in a multidisciplinary work reentry program: A case study. AB - The purpose of this paper is to present a case study of a patient with a history of low back pain and the use of isokinetic testing in tracking that patient through a work-reentry program. A 44-year-old male with a diagnosis of low back pain underwent a functional capacity evaluation and began a work-reentry program. Initial isokinetic testing revealed low torque outputs in both the trunk and knee flexion and extension tests as well as limited active range of motion. Coefficient of variation appeared to be relatively high and the patient seemed guarded in his movements during the testing. Psychological testing revealed a high fear of reinjury which may have influenced the initial test. Subsequent isokinetic testing performed on the tenth and twenty-fourth days of program and at 1 month post-program exhibited greater than expected increases in torque output. This could be due in part to a reduction in the fear of reinjury, a learning effect with repeated exposure to testing, and the patient's increased confidence in the use of unguarded movements. His trunk range of motion remained essentially the same throughout the serial testing. Pain in the back and left leg was slightly diminished despite an increase in strength and function. PMID- 24242329 TI - Evaluation after five years of the cancer genetic counselling programme of Valencian Community (Eastern Spain). AB - To evaluate the cancer genetic counselling programme in Valencian Community using intermediate indicators. Descriptive analysis of organisational and effectiveness indicators from the start in 2005 until December 2010: correct referral of patients according to the area from where they were referred (primary or hospital based care) and syndrome; families identified as having each syndrome; suitability of the genetic testing for individuals with a cancer diagnosis (index cases, IC) and relatives of ICs with mutations; family size; and results of genetic testing on genes, ICs and relatives. 9,942 individuals attended, 87.7 % were referred by hospital-based care and 8.4 % by primary care. 7,516 patients (79 %) fulfilled cancer genetic counselling criteria (82 % from hospital-based care and 46 % from primary care). Amongst those who fulfilled the criteria, 59 % of referrals were related to hereditary breast ovarian cancer syndrome and 32 % to hereditary non-polyposis colorectal cancer. ICs were found in 3,082 families (78.7 %) and genetic testing was carried out on 91.3 % of them. Pathogenic mutations were detected in 21.8 % of the ICs and the testing was then offered to their relatives (an average of 3 per IC). Pathogenic mutations were found in 54 % of the assessed relatives. Results in 5 years confirm the appropriateness of these facilities, as part of an integrated health service, to identify families and individuals with genetic risk to offer them personalized counselling. Improvements have to be made with regard to the information given to both health professionals and patients about the risk criteria for various syndromes. PMID- 24242330 TI - Repression of cathepsin E expression increases the risk of mammary carcinogenesis and links to poor prognosis in breast cancer. AB - Despite advances in detection and treatment for breast cancer (BC), recurrence and death rates remain unacceptably high. Therefore, more convenient diagnostic and prognostic methods still required to optimize treatments among the patients. Here, we report the clinical significance of the serum cathepsin E (CatE) activity as a novel prognostic marker for BC. Correlation analysis between the serum levels of CatE expression and clinicopathological parameters revealed that the activity levels, but not the protein levels, were negatively associated with the stages and progression of BC. Univariate and multivariate analyses demonstrated that the serum CatE activity was significantly correlated with favorable prognostic outcomes of the patients. The functional link of CatE expression to BC progression was further corroborated by in vivo and in vitro studies with mice exhibiting different levels of CatE expression. Multiparous CatE (-) (/) (-) mice spontaneously developed mammary tumors concomitant with morphological transformation and altered growth characteristics of the mammary glands. These alterations were associated in part with the induction of epithelial-mesenchymal transition and the activation of beta-catenin-dependent pathway in mammary cells. Loss of CatE strongly induced the translocation and accumulation of Wnt5a in the nuclei, thereby leading to the aberrant trafficking, maturation and secretion of Wnt5a and the impaired signaling. The interaction of CatE and Wnt5a was verified by proximity ligation assay and by knockdown or restoration of CatE expression in the mammary cells. Consequently, our data demonstrate that CatE contributes to normal growth and development of mammary glands through proper trafficking and secretion of Wnt5a. PMID- 24242331 TI - Association of microRNA-31 with BRAF mutation, colorectal cancer survival and serrated pathway. AB - BRAF is an important gene in colorectal cancers (CRCs) that is associated with molecular characterization and resistance to targeted therapy. Although microRNAs (miRNAs) are useful biomarkers of various cancers, the association between miRNA and BRAF in CRCs is undefined. Therefore, this study was conducted to identify a relationship between specific miRNA molecules and BRAF mutation in CRCs and serrated lesions. miRNA array was used for the measurement of 760 miRNAs in 29 CRCs. To assess the identified miRNAs, quantitative reverse transcription-PCR was performed on 721 CRCs, 381 serrated lesions and 251 non-serrated adenomas. Moreover, proliferation and invasion assays were conducted using cell lines. miRNA array analysis revealed that microRNA-31 (miR-31)-5p was the most up regulated miRNA in CRCs with mutated BRAF (V600E) compared with CRCs possessing wild-type BRAF (including cases with KRAS mutation). High miR-31 expression was associated with BRAF and KRAS mutations and proximal location (P < 0.0001). High miR-31 expression was related to cancer-specific mortality [multivariate hazard ratio = 2.06, 95% confidence interval: 1.36-3.09, P = 0.0008]. Functional analysis demonstrated that miR-31 inhibitor decreased cell invasion and proliferation. With regard to serrated lesions, high miR-31 expression was less frequently detected in hyperplastic polyps compared with other serrated lesions. In conclusion, associations were identified between miR-31, BRAF and prognosis in CRC. Transfection of miR-31 inhibitor had an antitumour effect. Thus, miR-31 may be a promising diagnostic biomarker and therapeutic target in colon cancers. Moreover, high miR-31 expression in serrated lesions suggested that miR-31 may be a key molecule in serrated pathway. PMID- 24242332 TI - Dominance and interloci interactions in transcriptional activation cascades: models explaining compensatory mutations and inheritance patterns. AB - Mutations in human genes encoding transcription factors are often dominant because one active allele cannot ensure a normal phenotype (haploinsufficiency). In other instances, heterozygous mutations of two genes are required for a phenotype to appear (combined haploinsufficiency). Here, we explore with models (i) the basis of haploinsufficiency and combined haploinsufficiency owing to mutations in transcription activators, and (ii) how the effects of such mutations can be amplified or buffered by subsequent steps in a transcription cascade. We propose that the non-linear (sigmoidal) response of transcription to the concentration of activators can explain haploinsufficiency. We further show that the sigmoidal character of the output of a cascade increases with the number of steps involved, the settings of which will determine the buffering or enhancement of the effects of a decreased concentration of an upstream activator. This exploration provides insights into the bases of compensatory mutations and on interloci interactions underlying oligogenic inheritance patterns. PMID- 24242333 TI - Serological characteristics of affected cattle during an outbreak of bovine enzootic encephalomyelitis caused by Akabane virus. AB - During an outbreak of bovine enzootic encephalomyelitis caused by the Akabane virus (AKAV) in 2010, 210 serum samples were collected from the affected cattle, and serological investigations for the AKAV were performed using a serum neutralization test (SNT) and an enzyme-linked immunosorbent assay (ELISA). The seropositive rates for SNT and ELISA were 90.0 and 85.2 %, respectively. The titers of SNT (log2) against the AKAV were higher than 4.0 in the highly affected cattle (80.0 %). This finding indicates that most affected cattle were infected with the AKAV and that strong immune responses against this virus were elicited in affected cattle. The strong immune response to the AKAV in cattle may provide insight into the occurrence of bovine encephalomyelitis caused by the AKAV. PMID- 24242334 TI - The effects of progesterone treatment following artificial insemination on the reproductive performance of dairy cows. AB - The objective of this study was to examine the effects of increasing circulating progesterone in multiparous Holstein cows, using an intravaginal progesterone implant between days 3 and 7 following fixed-time artificial insemination (FTAI). The animals were randomly assigned into two groups: (1) treatment group and (2) control (no treatment). The experiment took place during periods of high and mild temperatures. Pregnancy rates were evaluated by ultrasound at 30 and 60 days after FTAI; embryonic and fetal mortality rates were also evaluated on these dates. The temperature and humidity index on the day of FTAI were different (P < 0.05) during the times of interest, but it did not affect conception rates. Neither the conception rates at days 30 and 60 nor the embryonic and fetal mortality rates differed between the groups during either the high- or mild temperature periods (P > 0.05). Throughout the experimental period, the serum progesterone concentration was higher in the treatment group than in the control (P < 0.05). We conclude that the intravaginal progesterone implant inserted from days 3 to 7 following FTAI had no effect on conception rates at days 30 and 60 or on embryonic or fetal mortality rates but enhances the serum progesterone concentrations following treatment in multiparous Holstein cows during high- and mild-temperature periods. PMID- 24242336 TI - Propranolol for infantile haemangiomas: review of report of a consensus conference. PMID- 24242335 TI - Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice. AB - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and nontumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1 and Hnf1alpha genes were not mutated in tumors in mice treated with DEN+CCl4 . In contrast, the increased tumor incidence in mice treated with DEN+CCl4 was associated with marked epigenetic changes in liver tumors and nontumor liver tissue, including demethylation of genomic DNA and repetitive elements, a decrease in histone 3 lysine 9 trimethylation (H3K9me3) and promoter hypermethylation and functional downregulation of Riz1, a histone lysine methyltransferase tumor suppressor gene. Additionally, the reduction in H3K9me3 was accompanied by increased expression of long interspersed nucleotide elements 1 and short interspersed nucleotide elements B2, which is an indication of genomic instability. In summary, our results suggest that epigenetic events, rather than mutations in known cancer-related genes, play a prominent role in increased incidence of liver tumors in this mouse model of fibrosis-associated liver cancer. PMID- 24242339 TI - Editor's note. PMID- 24242338 TI - Computational prediction of actin-actin interaction. AB - Actin is one of the most abundant proteins in eukaryotic cells, where it plays key roles in cell shape, motility, and regulation. Actin is found in globular (G) and filamentous (F) structure in the cell. The helix of actin occurs as a result of polymerization of monomeric G-actin molecules through sequential rowing, is called F-actin. Recently, the crystal structure of an actin dimer has been reported, which details molecular interface in F-actin. In this study, the computational prediction model of actin and actin complex has been constructed base on the atomic model structure of G-actin. To this end, a docking simulation was carried out using predictive docking tools to obtain modeled structures of the actin-actin complex. Following molecular dynamics refinement, hot spots interactions at the protein interface were identified, that were predicted to contribute substantially to the free energy of binding. These provided a detailed prediction of key amino acid interactions at the protein-protein interface. The obtained model can be used for future experimental and computational studies to draw biological and functional conclusions. Also, the identified interactions will be used for designing next studies to understand the occurrence of F-actin structure. PMID- 24242340 TI - Higher plant terpenoids: A phytocentric overview of their ecological roles. AB - Characteristics of higher plant terpenoids that result in mediation of numerous kinds of ecological interactions are discussed as a framework for this Symposium on Chemical Ecology of Terpenoids. However, the role of terpenoid mixtures, either constitutive or induced, their intraspecific qualitative and quantitative compositional variation, and their dosage-dependent effects are emphasized in subsequent discussions. It is suggested that little previous attention to these characteristics may have contributed to terpenoids having been misrepresented in some chemical defense theories. Selected phytocentric examples of terpenoid interactions are presented: (1) defense against generalist and specialist insect and mammalian herbivores, (2) defense against insect-vectored fungi and potentially pathogenic endophytic fungi, (3) attraction of entomophages and pollinators, (4) allelopathic effects that inhibit seed germination and soil bacteria, and (5) interaction with reactive troposphere gases. The results are integrated by discussing how these terpenoids may be contributing factors in determining some properties of terrestrial plant communities and ecosystems. A terrestrial phytocentric approach is necessitated due to the magnitude and scope of terpenoid interactions. This presentation has a more broadly based ecological perspective than the several excellent recent reviews of the ecological chemistry of terpenoids. PMID- 24242341 TI - Metabolic costs of terpenoid accumulation in higher plants. AB - The net value of any plant trait can be assessed by measuring the costs and benefits associated with that trait. While the other contributors to this issue examine the possible benefits of terpenoids to plants, this article explores the metabolic costs of terpenoid accumulation in plants in the light of recent advances in terpenoid biochemistry. Terpenoids are more expensive to manufacture per gram than most other primary and secondary metabolites due to their extensive chemical reduction. The enzyme costs of making terpenoids are also high since terpenoid biosynthetic enzymes are apparently not shared with other metabolic pathways. In fact, plant cells may even possess more than one set of enzymes for catalyzing the basic steps of terpenoid formation. Terpenoids are usually sequestered in complex, multicellular secretory structures, and so storage costs for these substances are also likely to be substantial. However, not all of the processes involved in terpenoid accumulation require large investments of resources. For instance, the maintenance of terpenoid pools is probably inexpensive because there is no evidence that substantial quantities of terpenes are lost as a result of metabolic turnover, volatilization, or leaching. Moreover, plants may reduce their net terpenoid costs by employing individual compounds in more than one role or by catabolizing substances that are no longer needed, although it is still unclear if such practices are widespread. These findings (and other facets of terpenoid biochemistry and physiology) are discussed in relation to the assumptions and predictions of several current theories of plant defense, including the carbonnutrient balance hypothesis, the growth-differentiation balance hypothesis, and the resource availability hypothesis. PMID- 24242342 TI - Volatile herbivore-induced terpenoids in plant-mite interactions: Variation caused by biotic and abiotic factors. AB - Plants may defend themselves against herbivores by enhancing the effectiveness of natural enemies of herbivores. This is termed "indirect defense," which may be induced by herbivore damage. An important aspect of induced indirect defense is the attraction of the herbivore's natural enemies to infested plants by the plant emitting so-called "herbivore-induced synomone" (HIS) in response to herbivore damage. In this paper, we review the role of terpenoids in the induced indirect defense of plants against herbivorous mites. HIS are emitted from both damaged and undamaged areas of infested plants, and the composition of HIS varies among different plant species. The emission of HIS may also vary within a plant species, depending upon: (1) plant cultivar, (2) leaf growth stage, (3) the herbivore species that is attacking, and (4) abiotic conditions (light intensity, time of year, and water stress). Predatory mites cope with this variation of HIS by innate recognition as well as temporary specialization to a certain HIS via learning. PMID- 24242343 TI - In search of allelopathy in the Florida scrub: The role of terpenoids. AB - The hypothesis was tested that allelopathic agents released from fire-sensitive plants of the Florida scrub community deter the invasion of fireprone sandhill grasses. The structures of the constituents of four endemic scrub species,Conradina canescens, Calamintha ashei, Chrysoma pauciflosculosa, andCeratiola ericiodes, were established and their phytotoxic activity against two grasses of the sandhill was examined. Effects of the secondary metabolites from the above scrub species and their degradation products upon the germination and radicle growth of little bluestem (Schizachyrium scoparium) and green sprangletop (Leptochloa dubia), two native grasses of the Florida sandhill community, were determined. The studies included determination of the water solubility and release mechanism of terpenes and other allelopathic agents from the source plants and their aqueous transport to the target species. Some of the natural products were nontoxic until activated by light and/or oxidation after release from the source plant into the environment. PMID- 24242344 TI - Monoterpenes: Their effects on ecosystem nutrient cycling. AB - This article explores the evidence for monoterpenes to alter rates of nutrient cycling, with particular emphasis on the nitrogen (N) cycle, from an ecosystem perspective. The general N cycle is reviewed and particular processes are noted where monoterpenes could exert control. The theoretical and conceptual basis for a proposed mode of action by which monoterpenes effect the processes of N mineralization and nitrification is presented, along with recent developments. It is hypothesized that monoterpenes retained in litter enhance the frequency of fire, which in turn changes many N-cycling processes. Experimental support for these roles is presented that includes effects at the cellular level and progresses through populations and communities (microbial and invertebrate) involved in N mineralization and immobilization processes. Since many inhibitors of ammonium oxidation also inhibit methane oxidation, monoterpenes also may alter processes within the carbon cycle. Finally, areas for future research that appear most promising are suggested. PMID- 24242345 TI - Size effects in ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers. AB - The effects of the size of the ionic and neutral partners on ion-neutral complex mediated alkane eliminations from ionized aliphatic ethers were determined by obtaining metastable decomposition spectra and photoionization ionization efficiency curves. Increasing the size of the ionic partner decreases the competitiveness of alkane elimination with alkyl loss. This is attributed to decreasing attraction between the partners with increasing distance between the neutral partner and the center of charge in the associated ion. Increasing the size of the neutral partner lowers the threshold for alkane elimination relative to that for simple dissociation when the first threshold is above DeltaHf(products). This is attributed to increasing attraction between the partners with increasing polarizability of the radical in the complex. Adding a CH2 to the radical in a complex seems to increase the attraction between the partners by about 24 kJ mol(-1). PMID- 24242346 TI - Selective detection of the tolyl cation among other [C7H 7] (+) isomers by ion/molecule reaction with dimethyl ether. AB - The ion/molecule reaction of the tolyl cation with dimethyl ether has been investigated using triple quadrupole mass spectrometry. Three isomers with [C7H7](+) composition, the 3-tolyl, benzyl, and tropylium cations, were individually selected and reacted with dimethyl ether at a pressure of 1 mtorr in the second quadrupole (Q2) collision cell. Only the tolyl ion reacted to yield a methoxylated product ion peak at m/z 122. This reaction product having m/z 122 is postulated to be identical in structure with the molecular ion of 3-methyl anisole, as supported by thermochemical data and the similarity of the collision induced dissociation (CID) daughter ion mass spectra of the product ion and the molecular ion of authentic 3-methyl anisole. The daughter ion mass spectra of the three [C7H7](+) isomers during CID, by using a triple quadrupole mass spectrometer, are nearly identical; on the other hand, the analytical approach based on the ion/molecule reaction with dimethyl ether clearly exhibits distinct gas-phase chemistry reflecting structural differences among the isomers. Sot. PMID- 24242347 TI - Elucidating the structures of isomeric silylenium ions (SiC3H 9 (+) , SiC 4H 11 (+) , SiC 5H 13 (+) ) by using specific ion/molecule reactions. AB - Specific ion/molecule reactions are demonstrated that distinguish the structures of the following isomeric organosilylenium ions: Si(CH3) 3 (+) and SiH(CH3)(C2H5)(+); Si(CH3)2(C2H5)(+) and SiH(C2H5) 2 (+) ; and Si(CH3)2(i C3H7)(+), Si(CH3)2(n-C3H7)(+), Si(CH3)(C2H5) 2 (+) , and Si(CH3)3(pi-C2H4)(+). Both methanol and isotopically labeled ethene yield structure-specific reactions with these ions. Methanol reacts with alkylsilylenium ions by competitive elimination of a corresponding alkane or dehydrogenation and yields a methoxysilylenium ion. Isotopically labeled ethene reacts specifically with alkylsilylenium ions containing a two-carbon or larger alkyl substituent by displacement of the corresponding olefin and yields an ethylsilylenium ion. Methanol reactions were found to be efficient for all systems, whereas isotopically labeled ethene reaction efficiencies were quite variable, with dialkylsilylenium ions reacting rapidly and trialkylsilylenium ions reacting much more slowly. Mechanisms for these reactions and differences in the kinetics are discussed. PMID- 24242348 TI - O(-*) chemical ionization of carbonyl compounds. AB - The negative ion chemical ionization mass spectra of twentyeight C4 to C7 carbonyl compounds were recorded using the oxide radical anion O(-*) as reagent ion. As noted earlier, the reactions occurring include H(+) abstraction, H 2 (+*) abstraction, H- atom displacement, and alkyl radical displacement. In addition, the [M-2H](-) ions fragment further by alkyl radical elimination. The relative importance of these reactions depends strongly on molecular structure, with the result that isomer distinction frequently is possible. Where this is not possible, as for isomeric aldehydes, the collisional charge inversion mass spectra of common product ions provides isomer distinction. The H 2 (+*) abstraction reaction is shown to involve abstraction not only of two hydrogens from the same alpha-carbon but also, in part, abstraction of one hydrogen from each alpha-carbon. PMID- 24242349 TI - Ammonia laser desorption/chemical ionization with ammonium bromide: Fourier transform ion cyclotron resonance mass spectrometry of aromatic hydrocarbons. AB - Laser desorption/ionization combined with Fourier transform ion cylcotron resonance mass spectrometry (LD/FT/ICR/MS) is a proven technique for the analysis of nonvolatile materials. Unfortunately, LD tends to produce a large excess of neutral species compared to ions. Laser desorption followed by chemical ionization (LD/CI) by use of a reagent gas is a seIective and sensitive means of control in the analysis of nonvolatile compounds. In this article we demonstrate the technique of ammonia LD/CI by addition of a small amount of ammonium bromide (NH4Br) to an involatile sample, i.e., the ammonium salt is used in place of ammonia reagent gas. For various aromatic hydrocarbons, abundant (M + H)(+) ions are produced as a result of CI A primary advantage of this method in FT/ICR/MS is that selective LD/CI experiments may be conducted at low pressure as in pulsed valve CI (but without the need for pulsed valve operation), thereby providing the potential for obtaining high-resolution FT/ICR mass spectra. PMID- 24242350 TI - Information on the location of carbon-carbon double bonds in C6-C 23 linear alkenes from carbon addition reactions in a quadrupole ion trap equipped with a pulsed sample-inlet system. AB - Ion-molecule reactions of a number of alkene molecular ions with different neutral alkenes were studied in a quadrupole ion trap equipped with a pulsed sample-inlet system. The molecules studied include several isomeric unbranched hexenes, heptenes, octenes, and nonenes, as well as representative alkenes with ten, twelve, fourteen, and twenty-three carbon atoms. Transfer of structurally characteristic number of methylene units between the ionic and neutral reactants dominates the product distributions for all the alkenes studied, with the exception of 1-alkenes. Isomeric alkenes can be readily distinguished on the basis of their products from reactions with neutral alkenes. It is suggested that distonic intermediates are generated in these reactions, and that they fragment by alkene elimination after 1,2- and 1,5-hydride shifts. The ability to vary the reaction time, pressure of the neutral reagents, and the type of ions and neutral molecules present in the reaction chamber during each stage of the experiment sequence makes it possible to maximize the amount of structural information obtained for alkenes in these experiments. Use of CS 2 (+*) to generate the alkene molecular ion by charge exchange yields the same information without the need to carry out a mass-selection step for the ionized alkene. PMID- 24242351 TI - Negative ion tandem mass spectrometry of leukotriene E4, and LTE 4, metabolites: Identification of LTE 4, in human urine. AB - The sulfidopeptide leukotrienes, leukotriene E4, (LTE4,) and its N-acetyl derivative and several omega- and beta-oxidized metabolites of LTE4, have been analyzed by tandem mass spectrometry. [M-H](-) ions were produced by continuous flow fast atom bombardment, and collision-induced dissociation of these ions was studied by using a triple quadrupole instrument. The product ion spectra obtained were characteristic of the structure of LTE4, and mechanisms of ion formation were investigated by using deuterated compounds. beta-Elimination of the peptide portion of LTE4, by loss of CO2, and ethylene amine leaves the C-l carboxyl group ionized in the most abundant fragment ion for LTE4, and all metabolites. Tandem mass spectrometry of fast atom bombardment-generated anions from omega- and beta oxidized metabolites of LTE4, produced similar ions with only a minor influence of the third carboxyl group at the omega terminus evident. Tandem mass spectrometry was used to identify unequivocally the presence of unmodified LTE4, in a high performance liquid chromatography-purified fraction of urine from a normal healthy volunteer after infusion with LTE4. PMID- 24242352 TI - Understanding ion deceleration lenses: What are the simplicity/performance trade offs? AB - The traditional approach for obtaining highly collimated low energy (<200 eV) beams from high-energy (1-10 keV) sector mass spectrometers involves the use of a complex exponential deceleration lens assembly. Through ion optical modeling of the exponential lens and other less-complex lens designs, the fundamental features that contribute to deceleration lens performance are investigated. From this evaluation, a simple high-performance lens was designed, constructed, and characterized. The novel lens described here decelerates a 3-keV ion beam down to the 3-200-eV range while providing low angular divergence, excellent focusing, and good transmission. PMID- 24242353 TI - Standard definitions of terms relating to mass spectrometry : A report from the committee on measurements and standards of the American society for mass spectrometry. PMID- 24242354 TI - To the editor : J Am Soc Mass Spectrom 1991, 2, 349. PMID- 24242356 TI - A cross-sectional survey of repetitive behaviors and restricted interests in a typically developing Turkish child population. AB - This study examined compulsive-like behaviors (CLBs) which are higher-order types of Repetitive Behaviors And Restricted Interests (RBRIs) in typically developing children in Turkey. Caregivers of 1,204 children between 8 and 72 months were interviewed with Childhood Routines Inventory (CRI) by trained interviewers in a cross-sectional survey. Factor analysis of the CRI revealed two factor structures comprising "just right behaviors" and "repetitive/sensory sensitivity behaviors". CLB frequency peaked at 2-4 years with declines after age four. In contrast to the previous CRI studies reporting no gender difference, CLBs were more common in males in 12-23 and 48-59 month age groups on both total CLB frequency and repetitive/sensory sensitivity behaviors. Also ages of onsets for CRI items were somewhat later than reported in other samples. Our findings supported the findings of the previous CRI studies while also revealing new perspectives in need of further investigation. PMID- 24242357 TI - Progressive multifocal leukoencephalopathy after natalizumab discontinuation. AB - OBJECTIVE: To identify cases of laboratory- or biopsy-confirmed progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) who previously discontinued natalizumab (NTZ) for reasons unrelated to suspected or proven PML and assess PML risk factors in these cases. METHODS: We searched the US Food and Drug Administration Adverse Event Reporting System and MEDLINE for reports submitted from 2006 to 2012 of laboratory-confirmed PML with symptom onset >=30 days following NTZ withdrawal. We only analyzed cases where NTZ discontinuation was unrelated to suspected PML. RESULTS: Seventeen patients discontinued NTZ for reasons unrelated to PML but were subsequently diagnosed with the disease. The median NTZ duration was 47 monthly doses (range = 9-59 doses). All patients presented with compatible clinical symptoms within 6 months following withdrawal, and PML was confirmed by brain biopsy or by identifying JC virus in the cerebrospinal fluid by polymerase chain reaction. Immune reconstitution inflammatory syndrome (IRIS) was reported in 11 patients. Eleven patients (65%) received new MS treatments between NTZ discontinuation and PML confirmation. No deaths were reported. At NTZ withdrawal, 16 patients (94%) had >=1 PML risk factor, including NTZ duration >=2 years (n = 13), prior immunosuppressive agents (n = 8), and reported anti-JC virus seropositivity (n = 13). INTERPRETATION: NTZ-treated patients presenting clinically with PML within 6 months after NTZ withdrawal frequently have pre-existing PML risk factors. Clinicians need heightened awareness for new onset PML, IRIS, and MS relapse in evaluating neurological decline following NTZ discontinuation. Ann Neurol 2014;75:108-115. PMID- 24242358 TI - Hemodynamic and affective correlates assessed during performance on the Columbia card task (CCT). AB - The study aimed to test the potential of functional near-infrared spectroscopy (fNIRS) in combination with electrodermal activity (EDA) in a decision paradigm by means of the Columbia card task (CCT). The CCT is a dynamic decision task characterized by assessing subjects' risk-taking via eliciting voluntary stopping points in a series of incrementally increasingly risky choices. Using the combined fNIRS-EDA approach, we aim to examine the hemodynamic and affective correlates of both decision and outcome responses during performance on the CCT. Twenty healthy subjects completed the Cold and Hot CCT version while fNIRS over prefrontal cortex and EDA were recorded. Results showed that (1) in the decision phase fNIRS revealed larger total hemoglobin concentration changes [tHb] in the Cold as compared to the Hot CCT, whereas EDA revealed an opposite pattern with larger skin conductance responses (SCRs) to the Hot as compared to the Cold CCT. (2) No significant [tHb] signals or SCRs were found in the outcome phase. (3) Coherence calculations between fNIRS and EDA in the heart rate frequency showed a significant increase during the Hot as compared to the Cold CCT. Our findings designate fNIRS as suitable tool for monitoring decision-making processes. The combination of fNIRS and EDA demonstrates the potential of simultaneously assessing the interaction between hemodynamic and affective responses which can provide additional information concerning the relationship between these two physiological systems for various research areas. PMID- 24242360 TI - Haloperidol versus placebo for schizophrenia. AB - BACKGROUND: Haloperidol was developed in the late 1950s for use in the field of anaesthesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. OBJECTIVES: To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared with placebo. SEARCH METHODS: Initially, we electronically searched the databases of Biological Abstracts (1985 1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966 1998), PsycLIT (1974-1998), and SCISEARCH. We also checked references of all identified studies for further trial citations and contacted the authors of trials and pharmaceutical companies for further information and archive material.For the 2012 update, on 15 May 2012, we searched the Cochrane Schizophrenia Group's Trials Register. SELECTION CRITERIA: We included all relevant randomised controlled trials comparing the use of haloperidol (any oral dose) with placebo for those with schizophrenia or other similar serious, non affective psychotic illnesses (however diagnosed). Our main outcomes of interest were death, loss to follow-up, clinical and social response, relapse and severity of adverse effects. DATA COLLECTION AND ANALYSIS: We evaluated data independently and extracted, re-inspected and quality assessed the data. We analysed dichotomous data using risk ratio (RR) and calculated their 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD). We excluded continuous data if loss to follow-up was greater than 50% and inspected data for heterogeneity. We used a fixed-effect model for all analyses. For the 2012 update, we assessed risk of bias of included studies and used the GRADE approach to create a 'Summary of findings' table. MAIN RESULTS: Twenty-five trials randomising 4651 people are now included in this review. We chose seven main outcomes of interest for the 'Summary of findings' table. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (4 RCTs n = 472, RR 0.67 CI 0.56 to 0.80, moderate quality evidence). A further eight trials also found a difference favouring haloperidol across the six weeks to six months period (8 RCTs n = 307 RR 0.67 CI 0.58 to 0.78, moderate quality evidence). Relapse data from two trials favoured haloperidol at < 52 weeks but the evidence was very low quality (2 RCTs n = 70, RR 0.69 CI 0.55 to 0.86). Moderate quality evidence showed about half of those entering studies failed to complete the short trials (six weeks to six months), although, at up to six weeks, 16 studies found a difference that marginally favoured haloperidol (n = 1812, RR 0.87 CI 0.80 to 0.95). Adverse effect data does, nevertheless, support clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Moderate quality evidence indicates that haloperidol caused parkinsonism (5 RCTs n = 485, RR 5.48 CI 2.68 to 11.22), akathisia (6 RCTs n = 695, RR 3.66 CI 2.24 to 5.97, and acute dystonia (5 RCTs n = 471, RR 11.49 CI 3.23 to 10.85). Discharge from hospital was equivocal between groups (1 RCT n = 33, RR 0.85 CI 0.47 to 1.52, very low quality evidence). Data were not reported for death and patient satisfaction. AUTHORS' CONCLUSIONS: Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should be less favoured as a control drug for randomised trials of new antipsychotics. PMID- 24242361 TI - Scientific inquiry into rhinosinusitis: who is receiving funding from the National Institutes of Health? AB - OBJECTIVES/HYPOTHESIS: To evaluate National Institutes of Health (NIH) support for rhinosinusitis research and characterize the proportion of funding awarded to otolaryngologists. STUDY DESIGN: Analysis of the NIH RePORTER database. METHODS: Specialty and terminal-degree of primary investigators (PIs) for 131 projects spanning 364 fiscal years (1989 to present) were determined. Awards for projects examining rhinosinusitis were organized by size, academic department, and PI scholarly impact (using h-indices). Analysis of geographic and temporal funding trends was performed and organized by PI specialty. RESULTS: A total of 62.6% of projects were awarded to physicians, one-third of whom were otolaryngologists. Allergists/immunologists had greater median awards than otolaryngologist PIs (P = .02), and pediatric-trained PIs had a greater h-index than otolaryngologist PIs (P = .04). Although year-to-year fluctuation was noted, otolaryngologists have received approximately a quarter of total rhinosinusitis funding since 2000. PIs practicing in the south-Atlantic, east-north-central, and west-north-central states had the greatest funding totals, whereas otolaryngologists had a greater proportion of regional funding in the Pacific and east-south-central states than other regions. CONCLUSIONS: Inquiry into the mechanisms underlying rhinosinusitis and optimal therapeutic strategies represents an interdisciplinary venture. PIs in medicine and pediatric departments had greater funding for rhinosinusitis projects than individuals in otolaryngology departments, partly because of greater utilization of PhD faculty. Otolaryngology departments may consider increased recruitment of basic scientists interested in rhinosinusitis as a means to facilitate increased scholarship in this area. Encouraging pursuit of funding opportunities is critical for otolaryngologists, as well-funded practitioners may have greater opportunities to shape advances and serve as an advocate for their approaches. LEVEL OF EVIDENCE: NA. PMID- 24242359 TI - Epigenetics in immune-mediated pulmonary diseases. AB - Immune-mediated pulmonary diseases are a group of diseases that resulted from immune imbalance initiated by allergens or of unknown causes. Inflammatory responses without restrictions cause tissue damage and remodeling, which leads to airway hyperactivity, destruction of alveolar architecture, and a resultant loss of lung function. Epigenetic mechanisms have been demonstrated to be involved in inflammation, autoimmunity, and cancer. Recent studies have identified that epigenetic changes also regulate molecular pathways in immune-mediated lung diseases. Aberrant DNA methylation status, dysregulation of histone modifications, as well as altered microRNAs expression could change transcription activity of genes involved in the development of immune-mediated pulmonary diseases, which contributes to skewed differentiation of T cells and proliferation and activation of myofibroblasts, leading to overproduction of inflammatory cytokines and excessive accumulation of extracellular matrix, respectively. Aside from this, epigenetics also explains how environmental exposure influence on gene transcription without genetic changes. It acts as a mediator of the interaction between environmental factors and genetic factors. Identification of the abnormal epigenetic marks in diseases provides novel biomarkers for prediction and diagnosis and affords novel therapeutic targets for those difficult clinical problems, such as steroid-resistance and rapidly progressing fibrosis. In this review, we summarized the latest experimental and translational epigenetic studies in immune-mediated pulmonary diseases, including asthma, idiopathic pulmonary fibrosis, tuberculosis, sarcoidosis, and silicosis. PMID- 24242362 TI - Molecular properties of the Epstein-Barr virus BFRF3 gene. PMID- 24242364 TI - Molecular docking of heparin oligosaccharides with Hep-II heparin-binding domain of fibronectin reveals an interplay between the different positions of sulfate groups. AB - Fibronectin is a major component of the extracellular matrix and serves as support for cell adhesion and migration. Heparin and heparan sulfates (HS) have been reported to be high-affinity ligands for fibronectin. The strongest heparin/HS-binding site, named Hep-II, is located in the C-terminal repeat units FN12-14 of fibronectin. Mutational studies of recombinant fibronectin fragments and elucidation of the X-ray crystallographic structure of Hep-II in complex with heparin allowed localizing the main heparin/HS-binding site in FN13 to two parallel amino acid clusters: R1697, R1698, R1700 and R1714, R1716, R1745. Heparin, which is more sulfated than HS, is a better ligand for fibronectin, indicating that the sulfate density is important for the interactions. However, other studies demonstrated that the position of sulfate groups is also critical for high-affinity binding of the polysaccharides to fibronectin. In the current work, we used molecular docking of Hep-II domain of fibronectin with a series of differently sulfated dodecasaccharides of heparin to determine the implication of each sulfate position in the interaction. By using this approach, we confirmed the implication of R1697, R1698, R1700 and R1714 and we identified other amino acids possibly involved in the interaction. We also confirmed a hierarchic involvement of sulfate position as follows: 2S >> 6S > NS. Interestingly, the formation of stable complexes required a mutual adaptation between Hep-II domain and oligosaccharides, which was different according to the pattern of sulfation. Finally, we demonstrated that 3-O-sulfation of heparin stabilized even more the complex with Hep-II by creating new molecular interactions. Collectively, our models point out the complexity of the molecular interactions between heparin/HS and fibronectin. PMID- 24242363 TI - The flavivirus protease as a target for drug discovery. AB - Many flaviviruses are significant human pathogens causing considerable disease burdens, including encephalitis and hemorrhagic fever, in the regions in which they are endemic. A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication, such as the viral protease. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Because this cleavage is an obligate step of the viral life cycle, the flavivirus protease is an attractive target for antiviral drug development. In this review, we will survey recent drug development studies targeting the NS3 active site, as well as studies targeting an NS2B/NS3 interaction site determined from flavivirus protease crystal structures. PMID- 24242365 TI - Supplementation of suckling beef calves with different levels of crude protein on tropical pasture. AB - The effects of supplementation with different levels of crude protein on performance, intake and nutrient digestibility and efficiency of microbial protein synthesis in suckling beef calves on pasture were assessed. Fifty-five calves, with an average age of 100 days and an initial average body weight of 110 +/- 7.5 kg and their respective dams, were used. The experimental design was completely randomised with five treatments and 11 replications. The experimental treatments for calves were as follows: control = calves received only mineral mixture; supplementation levels = calves received supplement containing 8, 19, 30 or 41% of crude protein (CP, at a rate of 0.5% of body weight (BW)). The cows received only mineral mixture ad libitum. Supplemented calves had higher (P < 0.1) average daily gain (ADG). Protein levels showed a quadratic effect (P < 0.1) on average daily gain (ADG) of calves. There was no difference in total dry matter (DM) intake (P > 0.1). However, intake of dry matter forage (DMF) presented cubic profiles (P < 0.1), with CP levels in the supplements. Supplementation increased (P < 0.1) the digestibility of nutrients, except for the digestibility of neutral detergent fibre. Supplementation increased (P < 0.1) the production of microbial nitrogen and N losses in urine. It can be concluded that multiple supplementations optimise the performance of beef calves on creep feeding. The intake of supplements with CP levels between 8 and 30% partially replaces of the pasture ingested by calves and increases the digestibility of the diet. PMID- 24242367 TI - Editorial comments. PMID- 24242366 TI - Cancer risk among patients with coal workers' pneumoconiosis in Taiwan: a nationwide population-based study. AB - This study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow-up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow-up of 69,398 person-years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04-1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06-1.51). The SIRs of esophageal (1.76, 95% CI: 1.24 2.44), gastric (1.42, 95% CI: 1.13-1.76), liver and biliary tract (1.18, 95% CI: 1.01-1.37) and lung and mediastinal (1.45, 95% CI: 1.26-1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that age >= 60 years [hazard ratio (HR) 1.70, 95% CI: 1.41-2.05), male gender (HR = 1.79, 95% CI: 1.44-2.23) and liver cirrhosis (HR = 3.99, 95% CI: 2.89-5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development. PMID- 24242368 TI - Psychological factors affecting isokinetic trunk strength testing in patients with work-related chronic low back pain. AB - Psychological factors are assumed to play a major role in pain-related work disability. Assessment of pain-related disability using a functional capacity evaluation, usually includes assessment of trunk strength and range of motion. Isokinetic strength testing is a method used to measure strength and function of isolated muscles and has been reported to be an objective, quantifiable assessment of trunk function. Given that psychological factors are purported to play a role in pain-related disability, it would be important to assess their influence on measurement of physical function. The present study was conducted to assess the influence of psychological variables on isokinetic trunk strength performance. One hundred and eighty-six consecutive male outpatients referred to a work-rehabilitation center were given a functional capacity evaluation. All patients had been out of work for at least 3 months with the chief complaint of low back pain. The evaluation included isokinetic trunk strength testing and measurement of psychological variables (pain levels, distress, pain coping, pain behavior, somatization, expectation to return to work) that have been known to contribute to pain-related disability. Data analyses revealed significant correlations among psychological variables and measures of trunk strength and function. The findings provide support for a relationship between psychological variables and isokinetic strength testing performance. PMID- 24242369 TI - Reliability of a digital electroneurometer for the determination of motor latency of the median nerve. AB - Measurement of distal motor latencies of the median nerve are often part of electrodiagnostic studies used to verify a diagnosis of peripheral neuropathy. Since electrodiagnostic studies are time consuming, expensive, and impractical for large-scale screening of at-risk individuals, a portable digital electroneurometer was developed for measuring motor latencies as a screening tool for early detection of nerve compression syndromes, including carpal tunnel syndrome. The purpose of this study was to determine the intertester and intratester reliability of a digital electroneurometer in subjects with (n=12) and without (n=20) clinical signs of carpal tunnel syndrome. This study addressed only the reliability and not the validity of this device. Using a repeated measures design, three evaluators performed two distal motor latency tests on the median nerve of each of the subjects. Pearson product-moment correlations for intratester reliability ranged from 0.94 to 0.99, and the intraclass correlation coefficient for intertester reliability was 0.96. Two examiners obtained statistically larger latency values on the second test, although these differences are judged to be clinically insignificant. Use of an electroneurometer may expand motor latency testing to a wider variety of settings. PMID- 24242371 TI - New possibilities in safety performance and the control of workers' compensation costs. AB - This article describes successful behavioral interventions that improved safety performance and reduced workers' compensation costs in two corporations. The development of a four part program that: (1) shifted the paradigm for positive performance by workers and managers, (2) strengthened the community of work, (3) managed the crises of accidents, and (4) accelerated the return of injured employees to meaningful work is presented. In the two companies, lost time accidents were reduced by 95% and 87%, and accident costs were reduced by 90% and 70%, respectively. The results are discussed in terms of the critical roles played and choices made by managers in establishing a meaningful work culture, and the ethics which guide workers' and managers' behavior in decisions related to the use and abuse of the workers' compensation system. PMID- 24242372 TI - Clinical determination of work-relatedness in carpal tunnel syndrome. AB - The purpose of this study was to determine the diagnosis and work-relatedness of carpal tunnel syndrome (CTS) using standardized criteria in a series of cases that were referred for an independent medical examination with a prior diagnosis of work-related CTS. using a liberal case definition, only 65% of cases had CTS. Using Wisconsin's worker's compensation criteria for work-relatedness, only 55% of the cases had any work-related disorder, while only 37% of the cases had work related CTS. Duration of exposure was not significantly associated with work related vs. non-work-related CTS. It was noted that the development of non-work related CTS cases occurred uniformly across the various durations of exposure, as if unrelated to exposure. The symmetry of the disorder was unrelated to work relatedness, provided that the symmetry of the disease matched the symmetry of the exposure. Personal characteristics, such as obesity and diabetes, revealed no statistically significant associations with work-relatedness or CTS. The present findings illustrate application of a standard procedure for determining the work relatedness of CTS in a series of cases referred for independent medical examination. The results indicate that CTS is often, overdiagnosed and inaccurately linked to work. While the results may be limited by the method of determining work-relatedness, the findings indicate the importance of careful consideration of criteria for CTS and work-relatedness. When such an approach is taken, more targeted clinical management of the patient and appropriate intervention in the workplace should result. PMID- 24242370 TI - Predictive model to determine cost/benefit of early detection and intervention in occupational low back pain. AB - Low back pain related to work injury has major socioeconomic implications. Theoretically, the early detection of patients at risk for continued work disability after 6 months of work absence, and of those with a recurrence of pain (RP) and leave work once again, should be cost-effective if combined with effective intervention. The objective of this prospective research was to analyze the cost-effectiveness of a detection-intervention system (DIS) developed from a logistic predictive model of work status. A sample of newly injured workers (N=135 males) were assessed following a first episode of compensated low back pain. A predictive biopsychosocial profile was obtained from a series of univariate and multivariate regression analyses. Structural diagnosis, pain rating, length of inactivity before treatment, negative life changes, and self efficacy expectancies were found to be best predictors. With a correct classification rate of 72% the predictive model parameters (sensitivity and specificity) were chosen in order to reduce the number of false negatives (recurrence of pain or chronic patients not detected). The calculation of the cost/benefit proportions reveals that the detection-intervention system generates savings of up to $39,595 Can./100 patients a year. By combining low treatment expenses ($250 Can to $1,000 Can.) and increasing the success rates (40-75% return to work), the detection-intervention system is potentially more cost effective than the current approach without detection-intervention. PMID- 24242373 TI - Persistent pain and the injured worker: Integrating biomedical, psychosocial, and behavioral factors in assessment. AB - Health care providers are often asked to determine the level of impairment, degree of disability, and rehabilitation potential for injured workers. Compalints of persistent pain and especially compalaints that are: (1) not substantiated or that are disproportionate to physical pathology identified by physical examination and laboratory diagnostic procedures, or (2) that prove to be differentially responsive to identical treatments that are technically appropriate cause a great deal of frustration for health care providers and third party payers. Much of the confusion in this area relates to the minimal association between (1) the extent of impairment and degree of disability, and (2) between the magnitude of physical pathology and severity of the pain report. In this paper, we discuss factors that contribute tothe frustration and confusion and propose a comprehensive biobehavioral model that integrates biomedical, psychosocial, and behavioral variables. We also present an assessment model, the Multiaxial Assessment of Pain (MAP) patients, and describe operationalizations of the primary components of this model. PMID- 24242374 TI - Overexpression of Bcl-3 inhibits the development of marginal zone B cells. AB - The transcription factor Bcl-3 functions as a proto-oncogene via regulation of cell proliferation and apoptosis. Bcl-3 is an atypical member of the IkappaB family and plays a central role in the immune response through interactions with the NF-kappaB subunits p50 and p52. To investigate the impact of Bcl-3 on B-cell maturation and regulation, we generated mice that overexpress Bcl-3 specifically in B cells. Interestingly, these mice lack marginal zone B cells and exhibit a significant reduction in the number of B-1 B cells. Further, B cells from these mice are impaired in their proliferative capacity. Our data demonstrate that the overexpression of the transcription factor Bcl-3 inhibits germinal center formation, marginal zone B-cell development, and affects the B-1 B-cell compartment. PMID- 24242631 TI - Phenylalanine functionalized zwitterionic monolith for hydrophobic interaction electrochromatography. AB - A novel phenylalanine (Phe) functionalized zwitterionic monolith for hydrophobic electrochromatography was prepared by a two-step procedure involving the synthesis of glycidyl methacrylate based polymer monolith and subsequent on column chemical modification with Phe via ring-opening reaction of epoxides. Benefitting from the hydrophobicity of both methacrylate-based matrix and aromatic group of Phe, this monolith could exhibit good hydrophobic interaction for the separation. Typical RP chromatographic behavior was observed toward various solutes. The well-controlled cathodic or anodic EOF of the prepared column could be facilely switched by altering the pH values of running buffers. The separation mechanism of this Phe functionalized zwitterionic monolith is discussed in detail. Two mixed-mode mechanisms of RP/cation exchange and RP/anion exchange could be further realized on the same monolith in different pH condition of the mobile phase. Versatile separation capabilities of neutral, basic, and acidic analytes have been successfully achieved in this zwitterionic monolith by CEC method. PMID- 24242632 TI - Comparison of two models predicting IVF success; the effect of time trends on model performance. AB - STUDY QUESTION: How well does the recently developed UK model predicting the success rate of IVF treatment (the 2011 Nelson model) perform in comparison with a UK model developed in the early 1990s (the Templeton model)? SUMMARY ANSWER: Both models showed similar performance, after correction for the increasing success rate over time of IVF. WHAT IS KNOWN ALREADY: For counselling couples undergoing IVF treatment it is of paramount importance to be able to predict success. Several prediction models for the chance of success after IVF treatment have been developed. So far, the Templeton model has been recommended as the best approach after having been validated in several independent patient data sets. The Nelson model, developed in 2011 and characterized by the largest development sample containing the most recently treated couples, may well perform better. STUDY DESIGN, SIZE, DURATION: We tested both models in couples that were included in a national cohort study carried out in the Netherlands between the beginning of January 2002 and the end of December 2004. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed the IVF cycles of Dutch couples with primary infertility (n = 5176). The chance of success was calculated using the two UK models that had been developed using the information collected in the Human Fertilisation and Embryology Authority database. Women were treated in 1991-1994 (Templeton) or 2003-2007 (Nelson). The outcome of success for both UK models is the occurrence of a live birth after IVF but the outcome in the Dutch data is an ongoing pregnancy. In order to make the outcomes compatible, we used a factor to convert the chance of live birth to ongoing pregnancy and use the overall terms 'success or no success after IVF'. The discriminative ability and the calibration of both models were assessed, the latter before and after adjustment for time trends in IVF success rates. MAIN RESULTS AND THE ROLE OF CHANCE: The two models showed a similarly limited degree of discriminative ability on the tested data (area under the receiver operating characteristic curve 0.597 for the Templeton model and 0.590 for the Nelson model). The Templeton model underestimated the success rate (observed 21% versus predicted 14%); the Nelson model overestimated the success rate (observed 21% versus predicted 29%). When the models were adjusted for the changing success rates over time, the calibration of both models considerably improved (Templeton observed 21% versus predicted 20%; Nelson observed 21% versus predicted 24%). LIMITATIONS, REASONS FOR CAUTION: We could only test the models in couples with primary infertility because detailed information on secondary infertile couples was lacking in the Dutch data. This shortcoming may have negatively influenced the performance of the Nelson model. WIDER IMPLICATIONS OF THE FINDINGS: The changes in success rates over time should be taken into account when assessing prediction models for estimating the success rate of IVF treatment. In patients with primary infertility, the choice to use the Templeton or Nelson model is arbitrary. PMID- 24242633 TI - Offering predictive testing for Huntington disease in a medical genetics clinic: Practical applications. AB - Predictive testing for Huntington disease is presently offered in a select few medical genetics centers in the United States. This is in part due to the labor intensive counseling and psychological testing suggested by the research protocols. We discuss some specific suggestions for establishing programs for Huntington disease predictive testing within pre-existing medical genetics clinics to encourage more centers to offer presymptomatic testing. This will allow more at risk individuals the opportunity to consider predictive testing and cut down the expenses of traveling to the few predictive testing centers that currently exist. The counseling principals will remain similar to those discussed here, even following the identification of the Huntington disease mutation. PMID- 24242634 TI - Follow-up survey of pregnancies with diagnoses of chromosomal abnormality. AB - A small clinical survey was undertaken at East Carolina University School of Medicine to examine the factors which influenced the decisions of five families to continue pregnancies after a chromosomal abnormality was detected. Little has been published concerning the psychosocial effects after continuing pregnancies in which the fetus was diagnosed with a chromosome abnormality by amniocentesis. In order to identify the factors that influenced their decisions, an interview with each couple was undertaken using a 25-part questionnaire. This paper addresses the method of interviewing, case material, and background concerning each couple and the summary of the results. PMID- 24242635 TI - Introduction to 1992 Asilomar Conference papers. PMID- 24242636 TI - Ethnocultural diversity and genetic counseling training: The challenge for a twenty-first century. PMID- 24242637 TI - A teaching framework for cross-cultural genetic counseling. AB - The increasing diversity of American society has brought growing recognition of the need to bridge cultures in the delivery of genetic counseling services. New immigrants and members of diverse ethnic groups face multiple barriers to genetic counseling services. The need to train genetic counselors to deal with cultural diversity is especially crucial in the new genetic era, given the rapid expansion of available technology, with the resulting social and ethical ramifications. A framework for teaching cross-cultural issues in genetic counseling training programs is presented that can be implemented in step-wise fashion, consistent with available resources. Cross-cultural issues can be incorporated into existing teaching and training modalities by expanding the orientation from monocultural to multicultural. Relevant clinical experience, exploration of students' preconceptions and biases, reading materials, and lectures by invited speakers can all enhance students' knowledge and sensitivity. It is critically important that training programs furnish students with the basic tools necessary for the ongoing process of learning about cultural diversity. PMID- 24242638 TI - Minority recruitment into the genetic counseling profession. AB - In the past, genetic counseling training programs have had an abundance of applicants for the number of slots available. They have, however, had a very limited pool of minority applicants. At the June 1992 meeting of the genetic counseling training programs directors the topic of minority recruitment was explored. The resources and recommendations that resulted from this discussion can be used by other medical training programs. PMID- 24242640 TI - Genetic library. PMID- 24242639 TI - Update on master's genetic counseling training programs: Survey of curriculum content and graduate analysis summary. AB - The field of genetic counseling is a recognized specialty in medical genetics with the primary practitioners being masters degree prepared individuals. Since the inception of the first master's degree genetic counseling (MGC) training program in 1969, more than 1000 genetic counselors have graduated from established training programs in United States and Canada. The MGC programs involve a 2-year academic curriculum of both didactic course work and supervised clinical field work (clinical praticums). A recent survey of 17 existing MGC training programs (16 U.S. and 1 Canadian) reveals that MGC graduates average a total of 1349 actual contact hours (range 854-1952 hours) during their 2-year degree program course of study. Clinical experience gained through clinical practica accounts for 58% of required coursework, followed by didactic coursework in basic science (21%) and counseling (16%), respectively. A few programs also have requisite laboratory practica, which accounts for 5% of overall content hours. The 17 existing MGC programs produce approximately 100 graduates annually. Although the number of programs has grown since inception of the first MGC program in 1969, the mean number of graduates per program remains fairly constant. By year 2002, the estimated total number of master's degree trained genetic counselors will approach 2200. PMID- 24242641 TI - Identification of olfactory cues used in host-plant finding by diamondback moth,Plutella xylostella (Lepidoptera: Plutellidae). AB - Olfactory attraction of female diamondback moths (Plutella xylostella) to odors of intact and homogenized host plants, as well as individual compounds characteristic of host plants, were investigated by behavioral and electrophysiological methods. Moths were attracted to odors ofBrassica juncea andB. napus seedlings in a Y-tube bioassay. Solvent fractions of homogenizedB. juncea leaves were attractive to moths whether or not isothiocyanates (IC) were present. Moths were attracted in Y-tube bioassays and to field traps baited with individual ICs. Volatiles fromB. juncea andB. napus elicited an electroantennogram (EAG) response and were attractive in the Y-tube bioassay. Allyl IC was shown to be the attractive component in homogenized plant volatiles but was found to be virtually absent from intact plant volatiles. Gas chromatographic fractionation of intact plant volatiles revealed a terpene containing fraction to be most attractive to the moths. We were unable to isolate individual attractive compounds from this fraction. Our results suggest that certain elements of this fraction, possibly in combination, are important olfactory cues for host-plant finding by the diamondback moth with mustard oils playing an important and possibly synergistic role, particularly when plants are damaged. PMID- 24242642 TI - Reduced offspring production in bark beetleTomicus piniperda in pine bolts baited with ethanol and alpha-pinene, which attract antagonistic insects. AB - Bolts of Scots pine,Pinus sylvestris L., attacked by the bark beetleTomicus piniperda (L.) were baited with ethanol and alpha-pinene to attract antagonistic insects and thereby enhance their detrimental effects on the production of bark beetle progeny. Unbaited and caged bolts were included in the experiments as controls. Attraction of beetles to the bolts and subsequent emergence were estimated using traps. Six phloem-feeding species (potential competitors ofT. piniperda) and four predatory species were caught in significantly higher numbers at the baited bolts than at the unbaited ones. The number of offspring and the productivity ofT. piniperda were four to seven times higher in unbaited bolts than in baited bolts. Exclusion of other insects, by using cages, resulted in a nine-fold increase in the number ofT. piniperda offspring per square meter and productivity (offspring per egg gallery) compared with unbaited, exposed bolts.Hylurgops palliatus (Gyll.) (Scolytidae) andRhagium inquisitor (L.) (Cerambycidae) attacked both the baited and unbaited bolts, whereasAcanthocinus aedilis (L.) (Cerambycidae) andPytho depressus (L.) (Pythidae) reproduced almost exclusively in the baited ones. Large numbers of larvae ofThanasimus (Cleridae) andRhizophagus (Rhizophagidae) emerged from both the baited and unbaited bolts. Adults ofPlegaderus vulneratus (Panzer) andCylister linearis (Er.) (Histeridae) emerged almost exclusively from the baited bolts. The low progeny production ofT. piniperda in the baited bolts was attributed largely to the influence of adults ofRhizophagus andEpuraea (Nitidulidae), and larvae ofThanasimus andA. aedilis. PMID- 24242643 TI - Ecdysteroids fromPycnogonum litorale (Arthropoda, Pantopoda) act as chemical defense againstCarcinus maenas (Crustacea, Decapoda). AB - Pycnogonum litorale (Strom) is unpalatable to the common shore crabCarcinus maenas, a generalist predator in the pycnogonid's habitat. A feeding bioassay reveals that the crabs are deterred by ecdysteroids that occur in high levels in all developmental stages ofP. litorale. The total ecdysteroids in the pycnogonids reach 5.9*10(-4) M. The 20-hydroxyecdysone 22-acetate (20E22A), which is the predominant ecdysteroid in the pycnogonids, and 20-hydroxyecdysone (20E), the arthropod molting hormone, were tested for their antifeedant effect onC. maenas. When contained in food pellets in homogeneous concentrations, 20E and 20E22A significantly reduced food consumption at 1.25*10(-4) and 5.0*10(-4) molar levels, respectively. The present results demonstrate for the first time chemical defense in arthropods in a marine predator-prey relationship. Furthermore, they provide evidence that ES contained in one animal can act as feeding deterrents on another animal. PMID- 24242644 TI - Volatile shell-investigation cues of land hermit crabs: Effect of shell fit, detection of cues from other hermit crab species, and cue isolation. AB - Land hermit crab responses to volatile shell-investigation cues from land hermit crabs and from marine hermit crabs are analogous to the responses of marine hermit crabs to shell-investigation cues from marine crabs and from snails. Land hermit crabs attracted to shell cues are in worse-fitting shells and are more likely to investigate conspecifics' shells than are crabs attracted to feeding cues. Moving land hermit crabs from worse shells to better shells decreases the number of crabs investigating shells, while moving crabs from better shells to worse shells increases the number of crabs investigating shells. Gravid females have better-fitting shells than nongravid females or males. Crabs from two different populations in Panama have different shell fits and show different levels of responses to shell-investigation cues. Land hermit crabs respond to volatile shell-investigation cues from both land and marine hermit crabs, but marine hermit crabs do not respond to cues from land hermit crabs. A cue detection system for volatile cues most likely evolved in land hermit crabs during their transition from a marine to a terrestrial existence. Thus, the cues found in land hermit crabs and marine hermit crabs may be chemically similar. Volatile compounds collected from hermit crabs onto Tenax columns can be eluted with ethanol and act as shell-investigation cues in field assays. PMID- 24242645 TI - Male-produced aggregation pheromone ofCarpophilus obsoletus (Coleoptera: Nitidulidae). AB - Males ofCarpophilus obsoletus Erichson produce an aggregation pheromone to which both sexes respond. The pheromone was identified by GC-MS as (2E,4E,6E,8E)-3,5,7 trimethyl-2,4,6,8-undecatetraene (1), which is also a minor constituent of the pheromone blends ofC. hemipterus (L.),C. freemani Dobson, andC. lugubris Murray. The pheromone was synergized in wind-tunnel bioassays by propyl acetate, a "host type" coattractant. In a dose-response study, 50 pg of1, plus propyl acetate, was significantly more attractive than just propyl acetate. Pheromone emission from groups of 65 males, feeding on artificial diet, averaged 2.2 ng/male/day. Emissions from individual males were larger, averaging 72 ng/day and ranging as high as 388 ng/day. Synthetic1 was tested in a date garden in southern California (500 ug/rubber septum), using fermenting whole-wheat bread dough as the coattractant. The pheromone plus dough attracted significantly more beetles than dough alone (means were 4.2 and 0.0 beetles per week per trap). Captured beetles were 54% females. Field trap catches were highest during the months of July and August. PMID- 24242646 TI - Dermal gland secretions of tropical bont tick,Amblyomma variegatum (Acarina: Ixodidae): Biological activity on predators and pathogens. AB - When they are mechanically disturbed, all instars of the tropical bont tickAmblyomma variegatum exude droplets of a liquid on the dorsal, lateral, and ventral cuticle. These spread out and quickly evaporate. In this study, the possible role of these secretions was investigated in relation to predators and pathogens. In laboratory bioassays, it was demonstrated that the secretions from engorged larvae, nymphs, and females have an antibiotic activity against the bacteria speciesBacillus thuringiensis andSerratia marcescens, combined with a repellent effect on a potential predator, the fire-antSolenopsis geminata. PMID- 24242647 TI - Why are predator urines aversive to prey? AB - Predator odors often repel prey species. In the present experiments, we investigated whether changes in the diet of a predator, the coyote (Canis latrans) would affect the repellency of its urine. Furthermore, because predator odors have a high sulfur content, reflecting large amounts of meat in the diet, we investigated the contribution of sulfurous odors to repellency. Our results were consistent with the hypothesis that diet composition and sulfurous metabolites of meat digestion are important for the repellency of predator odors to potential prey. PMID- 24242648 TI - Intra- and interspecific avoidance of areas marked with skin extract from brook sticklebacks (Culaea inconstans) in a natural habitat. AB - The detection of a chemical alarm pheromone may allow receivers to avoid areas where a predator has captured the prey's conspecifics. We marked minnow traps with either brook stickleback (Culaea inconstans) skin extract or a control of distilled water and tested whether sticklebacks avoided the skin extract marked traps in a natural habitat. Significantly more sticklebacks were captured in traps marked with control water, thereby demonstrating avoidance of conspecific skin extract. The stickleback captured in traps marked with conspecific extract were significantly smaller than those captured in traps marked with control water, implicating ontogenetic factors (i.e., experience or physiological development) in the development of the response. We also captured significantly fewer finescale dace (Chrosomus neogaeus) and fathead minnows (Pimephales promelas) in traps marked with skin extract. These data suggest that dace and minnows may benefit by avoiding areas where predators have recently captured sticklebacks. PMID- 24242649 TI - Alarm responses in the crayfishOrconectes virilis andOrconectes propinquus. AB - Individuals of two species of crayfish (Orconectes virilis andO. propinquus) were tested in the laboratory for responses to chemicals released from physically damaged conspecifics. Individuals ofO. propinquus did not show an alarm response to crushed conspecifics. Individuals ofO. virilis responded to a water-borne substance released from crushed conspecifics by assuming an intermediate posture and ceasing movement. Similar alarm responses were shown by individuals ofO. virilis to crushed congeneric individuals (O. propinquus), and these responses were not eliminated by either freeze-thawing the crayfish used to prepare the signal or by treating freshly crushed crayfish with the enzyme trypsin. Individuals ofO. virilis showed strong feeding responses to solutions prepared from frozen fish flesh but showed a mixture of alarm and feeding responses to freshly killed fish. These results indicate that the alarm substance used byO. virilis is widespread. PMID- 24242650 TI - Aggregation pheromone for the pepper weevil,Anthonomus eugenii cano (Coleoptera: Curculionidae): Identification and field activity. AB - This study describes the identification of an aggregation pheromone for the pepper weevil,Anthonomus eugenii and field trials of a synthetic pheromone blend. Volatile collections and gas chromatography revealed the presence of six male specific compounds. These compounds were identified using chromatographic and spectral techniques as: (Z)-2-(3,3-dimethylcyclohexylidene)ethanol, (E)-2-(3,3 dimethylcyclohexylidene)ethanol, (Z)-(3,3-dimethylcyclohexylidene)acetaldehyde, (E)-(3,3-dimethylcyclohexylidene)acetaldehyde, (E)-3,7-dimethyl-2,6-octadienoic acid (geranic acid), and (E)-3,7-dimethyl-2,6-octadien-1-ol (geraniol). The emission rates of these compounds from feeding males were determined to be about: 7.2, 4.8, 0.45, 0.30, 2.0, and 0.30ug/male/day, respectively. Sticky traps baited with a synthetic blend of these compounds captured more pepper weevils (both sexes) than did unbaited control traps or pheromone-baited boll weevil traps. Commercial and laboratory formulations of the synthetic pheromone were both attractive. However, the commercial formulation did not release geranic acid properly, and geranic acid is necessary for full activity. The pheromones of the pepper weevil and the boll weevil are compared. Improvements for increasing trap efficiency and possible uses for the pepper weevil pheromone are discussed. A convenient method for purifying geranic acid is also described. PMID- 24242651 TI - Role of phenolic compounds in the antialgal activity of barley straw. AB - Barley straw decomposing in well-aerated water releases a substance(s) that inhibits algal growth. Phenolic compounds are toxic to algae but are unlikely to be present in sufficient quantities to account for the extended antialgal action of straw. However, straw is antialgal under conditions that may promote oxidation of phenolic hydroxyl groups to quinones; tannins are antialgal under similar conditions. The toxicity of authentic quinones towardsMicrocystis is confirmed; the quinones are some 10(3) times more antialgal than phenolic acids. The possibility that oxidized lignin derivatives may be involved in straw toxicity towards algae is discussed. PMID- 24242652 TI - Nature and role of sexual pheromones emitted by males ofAcrolepiopsis assectella (LEP.). AB - Seven compounds that do not exist in the extracts from legs of males have been isolated in the hair-pencil extracts of maleAcrolepiopsis assectella. By combining techniques of GC-MS and GC-FT-IR, six of these compounds have been identified. They are sixn-alkanes: hexadecane (C16), heptadecane (C17), octadecane (C18), nonadecane (C19), eicosane (C20), and heneicosane (C21). Twelven-alkanes of the homologous series, from the C14-C25 compounds were presented to virgin females, mated females, and males. At the end of the scotophase, four of then-alkanes (C16, C17, C19, C21) present in the hair-pencil extract induced the virgin females to adopt the acceptance posture after having induced the virgin females to remain stationary. The two othern-alkanes (C18 and C20) present in the extract have less effect on the females similar to then alkanes not present in the males. The blends tested do not seem to indicate any synergy between the most active compounds. The threen-alkanes with an odd number of carbons and the C16 compound would thus be the principle components of the male pheromone ofA. assectella. As well as their role of female aphrodisiac, they tend to make males and fertilized females flee. PMID- 24242653 TI - Natural and synthetic oviposition stimulants forCatolaccus grandis (Burks) females. AB - Oviposition behavior was elicited fromCatolaccus grandis (Burks) (Hymenoptera: Pteromalidae) females, an ectoparasitoid of the boll weevil,Anthonomus grandis Boheman (Coleoptera: Curculionidae), by smears of freshly cut cotton bolls or smears of extracts prepared with boll weevil damaged or undamaged cotton boll tissues. Oviposition behavior was also elicited fromC. grandis females by smears made withn-pentane,n-hexane,n-heptane, and isooctane. This is the first report of oviposition behavior elicited for any parasitoid by these short-chain saturated hydrocarbons (alkanes), introducing a new concept on the chemical mediation of parasitoid behavior during host selection. Oviposition behavior was also elicited fromC. grandis females by volatiles emanating from an artificial diet devoid of insect components that was specifically developed for the in vitro rearing of ectoparasitoids. The possible use of a synergistic combination ofn-hexane and diet to optimize the mechanized production of noncontaminated eggs is also discussed. PMID- 24242654 TI - Repellent properties of the host compound 4-allylanisole to the southern pine beetle. AB - The phenylpropanoid 4-allylanisole is a compound produced by loblolly pines (Pinus taeda L.), an abundant species in southern pine forests and a preferred host of southern pine beetle (Dendroctonus frontalis Zimmermann). Repellency of individual beetles was demonstrated in laboratory behavioral assays ofD. frontalis and other scolytids. Inhibition was demonstrated in natural populations ofD. frontalis using baited traps. In both tests, response to the inhibitory pheromone verbenone was used for comparison. In the laboratory, a higher proportion of newly emerged and reemergedD. frontalis responded negatively to 4 allylanisole than to verbenone. However, fewer reemergent than newly emerged individuals responded to either compound. In all field trials, the response ofD. frontalis to its attractant pheromone in funnel traps was significantly reduced by simultaneous release of 4-allylanisole. In most trials total reduction did not differ from verbenone; however, unlike verbenone, 4-allylanisole reduced male and female catches proportionally. Both compounds together did not significantly further reduce trap catch. The response of a major predator,Thanasimus dubius (F.), to the attractant pheromone ofD. frontalis, did not differ with the simultaneous release of either verbenone or 4-allylanisole. The results of preliminary field applications are presented and discussed. PMID- 24242655 TI - Influence of aggregation inhibitors (verbenone and ipsidenol) on landing and attack behavior ofDendroctonus brevicomis (Coleoptera: Scolytidae). AB - The influence of the aggregation inhibitors verbenone and ipsdienol on the response of western pine beetle,Dendroctonus brevicomis, to attractive host trees was investigated. Paired ponderosa pine trees (Pinus ponderosa) were baited with aggregation semiochemicals to stimulate mass attack. One tree in each pair received an inhibitor treatment consisting of five sets of two verbenone and two ipsdienol dispensers spaced 1 m apart vertically along the tree bole. Beetle landing was monitored with sticky traps on the tree bole, and attack density was assessed from bark samples removed four or seven days after baiting. The inhibitor treatment resulted in a significant reduction of both the numbers of beetles landing on trees and the density of attacking beetles compared to control trees (without inhibitors). The ratios of beetle landing density to attacking density were not different between inhibitor-treated and control trees, nor were the vertical distributions of beetles landing or attacking, suggesting that beetle behavior was primarily influenced at a longer range, prior to landing on the tree. Although the application of verbenone and ipsdienol did not preventD. brevicomis from attacking baited trees, our results suggest that when applied to unattacked (and unbaited) trees, their effectiveness at reducing the attack pressure might allow trees having a certain amount of resistance to survive attack by pioneer beetles. PMID- 24242656 TI - Differential toxicity of juglone (5-hydroxy-1,4-naphthoquinone) and related naphthoquinones to saturniid moths. AB - The preferred hosts of the saturniid mothActias luna include members of the Juglandaceae, whose foliage contain the toxin juglone (5-hydroxy-1,4 naphthoquinone). The performance ofActias luna andCallosamia promethea was compared when fourth-instar larvae of each were fed birch foliage, a mutually acceptable food plant, or birth supplemented with 0.05% (w/w) juglone.A. luna fed juglone exhibited no changes in developmental time or mortality compared to a diet without juglone. In contrast, juglone-supplemented diets, when fed toC. promethea, caused negative growth rate, and a 3.6-fold decrease in consumption rate. The performance ofA. luna also was compared on birch and walnut; larvae developed and grew more rapidly on an all-walnut vs. an all-birch diet. To examine the effect of 1,4-naphthoquinone structure onA. luna survival, first instars were fed on birch supplemented with varying concentrations of juglone (J), menadione (M), plumbagin (P), or lawsone (L). In diets supplemented at 0.05% (w/w), none of the compounds produced effects significantly different from controls. In diets supplemented at 0.5% (w/w), the treatments produced significant toxic effects in the order P>M=L>J for mortality, and P>L>M=J for increased developmental time. Late-instarA. luna are clearly resistant to juglone compared toC. promethea, and early-instarA. luna are resistant to several related 1,4-naphthoquinones. These results suggest a chemical basis for host choice among saturniids. In addition, the luna-walnut system may be a valuable model for studying quinone detoxication. PMID- 24242657 TI - Identification and field evaluation ofAnomala octiescostata (Coleoptera: Scarabaeidae) sex pheromone. AB - Using GC-EAD, the sex pheromone of the scarab beetleAnomala octiescostata was identified to be a 8:2 binary mixture of (R,Z)-5-(-)-(oct-1-enyl)oxacyclopentan-2 one and (R,Z)-5-(-)-(dec-1-enyl)oxacyclopentan-2-one. These semiochemicals have been also reported as sex pheromone constituents of otherAnomala species, either geographically or seasonally isolated fromA. octiescostata. Synthetic sex pheromone was highly attractive in the field; 0.1 mg captured significantly more males than two virgin females. Buried traps were significantly more attractive than those positioned at 30, 90, and 150 cm above the ground. In a dose-response test (0.1-100 mg), no saturation due to overdose of pheromone was observed, but in most cases, two dosages differing by 10-fold were not significantly different. Response of males to traps baited with different ratios of the two components was tested in two experiments with randomized blocks and Latin-square designs. Deviation from the natural ratio (8:2) of sex pheromone did not significantly diminish the response of males. Peak flight activity of beetle was recorded at 9:00-10:00 AM JST on sunny days in the end of April 1993. PMID- 24242658 TI - Plant response to eggs vs. Host marking pheromone as factors inhibiting oviposition byPieris brassicae. AB - Pieris brassicae L. butterflies secrete miriamides onto their eggs. These avenanthramide alkaloids are strong oviposition deterrents when sprayed onto a cabbage leaf. However, these compounds could not be detected in cabbage leaves from which egg batches had been removed two days after deposition and that still showed oviposition deterrency. It was concluded that the miriamides were not directly responsible for the avoidance by females of occupied leaves while searching for an oviposition site. Evidence was obtained that cabbage leaves themselves produce oviposition deterrents in response to egg batches. Fractions containing potent oviposition deterrents could be isolated from surface extracts of leaves from which previously laid egg batches had been removed. The term host marking pheromone that was used previously is not applicable in this case. PMID- 24242659 TI - The scarab beetleAnomala albopilosa sakishimana utilizes the same sex pheromone blend as a closely related and geographically isolated species,Anomala cuprea. AB - Two components were identified in the sex pheromone system of the green chafter,Anomala albopilosa sakishimana Nomura: (R,Z)-5-(-)-(oct-1 enyl)oxacyclopentan-2-one (buibuilactone) and (R,Z)-5-(-)-(dec-1 enyl)oxyacyclopentan-2-one (japonilure), which have been previously identified as sex pheromone constituents ofA. cuprea andA. octiescostata. A female-specific minor component, (R,E)-5-(-)-(oct-1-enyl)oxacyclopentan-2-one, did not seem to be involved in pheromonal communication because it was not EAD active, but its role remained unclear. A synthetic blend of the two components captured significantly more beetles than any other treatments. Nevertheless, the fact that both the synthetic sex pheromone and field-captured female beetles were weak lures convinced us that the sex pheromone system may be only part of a complex communication system, probably involving plant volatiles. Although the sex pheromone was released during both the scotophase and photophase, there was an increase of 60% in the photophase. PMID- 24242661 TI - Mimosine-inhibited seed germination, seedling growth, and enzymes ofOryza sativa L. AB - The effect of mimosine (50 ppm and 100 ppm concentrations) onOryza sativa (rice) seed germination; root and shoot growth, i.e., length and fresh weight of seedlings; activities of nitrate reductase, peroxidase, catalase, and IAA oxidase were investigated. Significant inhibition in seed germination and shoot length was noted. Root length was inhibited by 100 ppm mimosine; however, the 50 ppm was not significant. Root and shoot fresh weight was not significantly inhibited by the tested concentrations of mimosine. Significant inhibition in activities of nitrate reductase, peroxidase and its isoenzymes, catalase, and IAA oxidase was observed. Ecophysiological implications of mimosine phytotoxicity are discussed. PMID- 24242660 TI - Cuticular hydrocarbons of the paper wasp,Polistes fuscatus: A search for recognition pheromones. AB - The cuticular chemicals of 124 individual wasps (foundresses and workers) from 23 colonies ofPolistes fuscatus were analyzed. The compounds identified, all of which were hydrocarbons, were similar to those of other vespid wasps in that the bulk of the hydrocarbons were 23-33 carbons in chain length. However, the hydrocarbon profile ofP. fuscatus differed from those of its congeners in its proportions of straight-chain alkanes, methylalkanes, and alkenes. Three of the 20 identified hydrocarbons, 13- and 15-MeC31, 11,15- and 13,17-diMeC31, and 13-, 15-, and 17-MeC33, had properties postulated for recognition pheromones: colony specificity, efficacy in assigning wasps to the appropriate colony, heritability, lack of differences between foundresses and workers, and distinctive stereochemistry. PMID- 24242662 TI - Kairomone from dandelion,Taraxacum officinale, attractant for scarab beetleAnomala octiescostata. AB - The attraction of the scarab beetleAnomala octiescostata to dandelion,Taraxacum officinale, was demonstrated to be chemically mediated by a mixture ofcis-3 hexenyl acetate, benzaldehyde, phenylacetaldehyde, benzyl alcohol, phenethyl alcohol, phenylacetonitrile, and benzyl benzoate, in the ratio 4:8:14:3:5:19:11. Combination of the synthetic kairomone and sex pheromone (buibuilactone + japonilure, 8:2), significantly increased the total catches ofA. octiescostata. Catches of male (but not female) beetles were significantly higher with the kairomone-pheromone blend than with kairomone alone. The synergistic effect of the kairomone from dandelion on the attractiveness did not significantly differ from that of a food-type lure, anethol, geraniol, and phenethyl propionate (9:0.5:0.5). The latter combined with the synthetic sex pheromone resulted in better attraction of female (but not male)A. octiescostata than the sex pheromone alone. PMID- 24242663 TI - Sex pheromone of oriental beetle,Exomala orientalis: Identification and field evaluation. AB - A gas chromatograph coupled with a behavioral bioassay was used to identify two sex pheromone components, 7-(Z)- and 7-(E)-tetradecen-2-one of the Oriental beetle (OB),Exomala orientalis. Field experiments showed that the blend of the two isomers (Z:E, 7:1) was not significantly more attractive than theZ component alone. The best performance of traps baited with the synthetic sex pheromone was achieved when they were set with the pheromone device at 30 cm above the ground. Catches in traps baited with 1 and 10 mg were not significantly different, but they were higher (2.9-fold) than captures in traps loaded with 0.1 mg of the pheromone. Further investigations by GC-EAD revealed the presence of a possible minor component, but the small amount of material prevented its identification. 2 (E)-Nonenol, with the same retention time as the natural product, did not affect the attractancy of the synthetic sex pheromone. GC-EAD screening of previously identified sex pheromones of scarab beetles showed that male antennae of the Oriental beetle responded to japonilure, but it showed neither synergism nor inhibition to the OB sex pheromone. PMID- 24242664 TI - Trail pheromone of leaf-cutting antAcromyrmex subterraneus subterraneus (Forel). AB - The trail pheromone ofAcromyrmex subterraneus subterraneus consists simply of the heterocyclic ester methyl 4-methylpyrrole-2-carboxylate in the venom reservoir of workers at about 1.2 ng/ant. No pyrazines were detected, and no enhancement of trail-following was observed when pyrazines were added to the pyrrole compound. PMID- 24242665 TI - Plant-natural enemy association in the tritrophic system,Cotesia rubecula-Pieris rapae-brassiceae (cruciferae): I. Sources of infochemicals. AB - The role of airborne infochemicals in host selection by the parasitoidCotesia rubecula (Marshal) (Hymenoptera: Braconidae) was examined in a wind tunnel. To elucidate the role of volatile chemicals in attractingC. rubecula to cabbage infested by the host [Pieris rapae L. (Lepidoptera: Pieridae)], the potential sources of volatiles related toP. rapae infestation on cabbage were tested individually. The responses of females to nonhost plant species, bean and geranium, as well as to frass of a nonhost lepidopteran were also examined.C. rubecula was attracted to cabbage previously infested byP. rapae and to frass and regurgitate ofP. rapae. No attraction was observed to larvae ofP. rapae alone. Females were also attracted to mechanically damaged cabbage, cabbage previously infested byPlutella xylostella L. (Lepidoptera: Plutellidae) (a nonhost lepidopteran herbivore), and cabbage previously infested by snails (a nonhost, noninsect herbivore). Intact cabbage, bean, and geranium plants elicited no attraction. A low frequency of attraction was observed to mechanically damaged bean and geranium. Attraction was also observed to frass ofP. xylostella. Volatiles from cabbage related to damage, and volatiles from frass and regurgitate of the host seem to play an important role in guidingC. rubecula to plants infested by its host. PMID- 24242666 TI - Plant-natural enemy association in the tritrophic systemCotesia rubecula-Pieris rapae-brassicaceae (cruciferae): II. Preference ofC. rubecula for landing and searching. AB - The responses of the parasitoidCotesia rubecula to differently damaged cabbages were recorded during a series of choice tests. To determine if flyingC. rubecula can discriminate differences in the blend of volatiles emitted by cabbages damaged by different causes and how plant volatiles released from a distant source affect the searching behavior ofC. rubecula once searching on a plant, wasps were presented with a choice of plants located one behind the other and separated by a distance of 15 cm. The sources of damage were: cabbage damaged by the host (Pieris rapae), by a nonhost lepidopteran herbivore (Plutella xylostella), by a nonhost, noninsect herbivore (snail), and by mechanical means. The results showed that the site of first landing and the time spent searching on the leaves was influenced by the type of damage inflicted on plants. Wasps preferred to land on cabbages damaged by host and nonhost species of Lepidoptera over those damaged by snails and mechanical means. No preference was observed for first landing between cabbages damaged by the two species of Lepidoptera or between cabbages damaged by snails and mechanical means. Cabbage damaged byP. rapae was searched most intensively, followed by cabbage damaged byP. xylostella, cabbage damaged by snails, and cabbage damaged by mechanical means.C. rubecula differentiates between the volatile blends emitted by differently damaged cabbages, and it is attracted to volatiles related to recent lepidopteran damage. Wasps searched longer on freshly damaged than on leaves with older damage. PMID- 24242667 TI - Aggregation pheromone system of adult gregarious desert locust schistocerca gregaria (forskal). AB - Six electrophysiologically active aromatic compounds, viz., anisole, benzaldehyde, veratrole, guaiacol, phenylacetonitrile, and phenol, were identified in the volatiles of older-adult male desert locust. Young adults and females of all age groups produced none or only trace quantities of these compounds. Comparison of the aggregation responses of young and older adults to the crude, older-adult, volatile extract and different synthetic blends of the six compounds showed that the aggregation pheromone system of the adult gregarious locust consists of phenylacetonitrile, guaiacol, phenol, and benzaldehyde. Like the crude volatile extract of older males, neither the synthetic blend of the six compounds nor the adult pheromone blend evoked any significant aggregation responses from nymphs. These results confirm our previous report of sexual differentiation in the production of adult aggregation pheromone in the desert locust and of the evidence of two distinct aggregation pheromone systems in the two stages of the insect. PMID- 24242668 TI - Chemical suppression of feeding in larval weakfish (Cynoscion regalis) by trochophores of the serpulid polychaeteHydroides dianthus. AB - We studied the effect of exudates from trochophore larvae of the polychaeteHydroides dianthus on feeding in larval weakfish (Cynoscion regalis). Laboratory prey consisted ofH. dianthus trochophores and/or comparably sized rotifers (Brachionus plicatilis). When experiments were conducted in filtered seawater, ingestion of rotifers was always greater than ingestion of trochophores. However, consumption of rotifers was depressed when water fromH. dianthus cultures (=trochophore water) was the experimental medium. The same effect was noted whether we added trochophore water from polychaete cultures that were two or five days postfertilization. However, no effect was noted when we used water from rotifer cultures. We concluded thatH. dianthus trochophores release a water-soluble compound that inhibits feeding in weakfish larvae. PMID- 24242669 TI - Simultaneous effects of ferulic andp-coumaric acids on cucumber leaf expansion in split-root experiments. AB - Experiments were conducted to determine how plant responses to mixtures of allelochemicals may change as the proportion of roots in contact with allelochemicals is modified. Thirteen-day-old cucumber seedlings were treated with ferulic and/orp-coumaric acid in a split-root nutrient culture system. Leaf areas were determined just prior to treatment and at harvest, 24 hr after treatment. Ferulic acid was more inhibitory to cucumber leaf expansion thanp coumaric acid. The effects of ferulic andp-coumaric acids on leaf expansion were additive. For individual acids, mixtures of ferulic andp-coumaric acids in the same container and combinations of ferulic andp-coumaric acids in separate containers, the inhibition of leaf expansion was directly related to the product of the concentration of the acid(s) and the proportion of roots treated with the acid(s). Pretreatment with 0.2 or 0.4 mM ferulic acid and subsequent treatment with 0.5 mM ferulic acid failed to show evidence of acclimation by cucumber seedlings. PMID- 24242670 TI - Chemical composition of North American bee propolis and biological activity towards larvae of greater wax moth (Lepidoptera: Pyralidae). AB - Bee propolis is a sticky amalgamation of plant resins collected by honeybees (Apis mellifera L.) and used in the hive for filling cracks and repairing combs. Propolis contains a diversity of compounds of plant origin, and is reported to have medicinal, antimicrobial, insecticidal, and phytotoxic properties. We examined the physical and chemical composition of North American samples of bee propolis from several sites in North America and tested for bioactivity against larvae of the greater wax moth (Galleria mellonella L.), a common apiary pest. The amount of methanol-extractable resin in samples from Ohio and Georgia ranged from 24% to 79% by weight. Propolis collected from hives in Ohio was more chemically diverse (over 30 compounds detected by paper chromatography) than material from south Georgia (fewer than 10 major compounds) and contained a lower proportion of methanol-insoluble beeswax. The paper chromatographic surveys revealed little variation in the chemical profile of specific hives over a six month period and no differences between propolis from adjacent hives. Four flavonoids were identified from propolis collected in Ohio: kaempferol, galangin, 3,3'-dimethoxyquercetin and 3-methoxykaempferol. When mixed into artificial diet, fractionated propolis reduced larval growth of the greater wax moth, but not dramatically. An array of phenolics reported from propolis (caffeic acid, chrysin, ferulic acid, galangin, kaempferol, and quercetin) were bioassayed individually for effects on larvae, but none reduced larval growth at the concentrations tested, suggesting that wax moths are tolerant of some phenolics in their diet. PMID- 24242672 TI - Integrated self-organization of transitional ER and early Golgi compartments. AB - COPII coated vesicles bud from an ER domain termed the transitional ER (tER), but the mechanism that clusters COPII vesicles at tER sites is unknown. tER sites are closely associated with early Golgi or pre-Golgi structures, suggesting that the clustering of nascent COPII vesicles could be achieved by tethering to adjacent membranes. This model challenges the prevailing view that COPII vesicles are clustered by a scaffolding protein at the ER surface. Although Sec16 was proposed to serve as such a scaffolding protein, recent data suggest that rather than organizing COPII into higher-order structures, Sec16 acts at the level of individual COPII vesicles to regulate COPII turnover. A plausible synthesis is that tER sites are created by tethering to Golgi membranes and are regulated by Sec16. Meanwhile, the COPII vesicles that bud from tER sites are thought to nucleate new Golgi cisternae. Thus, an integrated self-organization process may generate tER-Golgi units. PMID- 24242674 TI - Phylogeny of ten species of the genus Hordeum L. as revealed by AFLP markers and seed storage protein electrophoresis. AB - The phylogenetic relationships of 60 accessions representing ten species of the genus Hordeum were investigated based on AFLP markers and seed storage protein SDS-PAGE electrophoresis. A total of 339 AFLP polymorphic markers were scored as a result of fingerprinting the studied taxa using seven AFLP primer combinations, whereas 46 polymorphic protein bands resulted from the water soluble and water non-soluble seed storage protein electrophoresis. The phylogenetic tree deduced from AFLP analysis is concordant in a large extent with that deduced from seed storage protein electrophoresis. The studied taxa were clustered according to their genome type into two main groups representing the Old and New World's species. Inside each group the species were clustered according to their genome type. Highly significant cophenetic correlation coefficient was obtained between both AFLP (0.96) and seed storage protein (0.89) indicating the reliability of the results. PMID- 24242673 TI - Association study of promoter polymorphisms in the CETP gene with longevity in the Han Chinese population. AB - The cholesteryl ester transfer protein (CETP), which is involved in the regulation of reverse cholesterol transport and metabolism of high-density lipoprotein cholesterol, has been proposed as a candidate gene for human longevity. SNPs in the promoter region of the CETP gene is likely important in regulation of the expression of the CETP gene. To explore the potential effects of the promoter polymorphisms in the CETP gene on longevity, we investigated the promoter polymorphisms in a sample of long-lived (>= 90 years old) Han Chinese collected from Southwestern China (N = 380). By resequencing 934 bp of the promoter region, genotypes of four SNPs (-573A/G, -629A/C, -971A/G, -1046T/C) were examined in this sample. However, no association could be confirmed between longevity and these SNPs or haplotypes inferred from them. A novel rare variant 573A/G was found and was found in heterozygote state only in five persons in the Longevity group. But it was not statistically significant (p = 0.075). We also examined this novel polymorphism -573A/G in another Han Chinese sample from Yunnan province, and it was not associated with longevity. The results from both samples suggest that there is likely no association of the CETP gene promoter polymorphisms with longevity, at least among Han Chinese. PMID- 24242675 TI - Treatment of extensive metastatic colorectal cancer to the liver with systemic and hepatic arterial infusion chemotherapy and two-stage hepatic resection: the role of salvage therapy for recurrent disease. AB - BACKGROUND: Two-stage hepatectomy (TSH) has been adopted as a treatment modality for resection of advanced colorectal liver metastases (CRLM). This study analyzed the recurrence pattern, salvage rate, and survival after TSH combined with systemic and regional chemotherapy. METHODS: A retrospective review of a prospective database identified patients who underwent a TSH for CRLM was performed and outcome data analyzed. RESULTS: From September 2000 to May 2009, a total of 40 patients were eligible for TSH, and 88 % completed both resections. Of the 35 resected patients, the median number of tumors was 8, with 38 % having a tumor >5 cm and 35 % having a carcinoembryonic antigen value >200 ng/ml. All patients received systemic chemotherapy, and 86 % received regional therapy with hepatic artery infusion. Median follow-up for survivors was 40 months; median disease-specific survival was 52 months, and 5-year disease-specific survival was 49 %. The combined rate of major complication for all procedures was 45 % with no operative deaths. Median recurrence-free survival was 11 months with a 3-year probability of recurrence of 81 %. Disease recurrence occurred in 27 patients (77 %), with the liver (42 %) and lung (37 %) being the most common sites. Sixteen of these patients (60 %) underwent salvage therapy via either surgery and/or ablation, 7 (44 %) of whom were free of disease at a median follow-up of 54 months. CONCLUSIONS: TSH combined with systemic and hepatic artery infusion chemotherapy is an effective treatment strategy for selected patients with advanced CRLM. These patients are at considerable risk of local and distant recurrence; however, the majority can be salvaged, and long-term survival can be achieved. PMID- 24242676 TI - Salvage surgery for residual primary and locally recurrent anal squamous cell carcinoma after chemoradiotherapy in HIV-positive individuals. AB - BACKGROUND: The treatment of anal cancer in human immunodeficiency virus (HIV) patients-as in the general population-is primarily with chemoradiotherapy (CRT), and abdominoperineal resection of residual or recurrent primary disease. The aim of this study was to evaluate the extent of residual primary disease and local recurrence as well as the outcome of salvage surgery after CRT for anal carcinoma in HIV-positive individuals. METHODS: We retrospectively studied HIV-positive anal carcinoma patients treated between February 1989 and November 2012 in a specialist London unit. Extent of residual primary disease, local recurrence after CRT, postoperative complications, and survival after salvage surgery were evaluated. RESULTS: Complete response was experienced in 44 of 53 (83%) of HIV patients treated with CRT for anal carcinoma. One patient (2.3%) developed local recurrence. Nine patients (eight residual primary disease after CRT and one local recurrence) underwent salvage surgery after CRT. There were no perioperative deaths, and perioperative CD4 counts were sustained. Complications occurred in five patients (55%). Median interval to complete perineal healing was 4 months (range 2-11 months), and median hospital stay was 29 days. Survival (median 16 months) was 25% at 2 years from salvage surgery. CONCLUSIONS: Results in HIV positive patients receiving highly active antiretroviral therapy (HAART) suggest that loss of HIV sensitivity to HAART can be avoided, but that there is increased postoperative morbidity that may be related to HIV disease. Survival was comparable to that for salvage therapy after optimal CRT in non-HIV anal carcinoma patients. PMID- 24242677 TI - A comparison of five competing lymph node staging schemes in a cohort of resectable gastric cancer patients. AB - BACKGROUND: New classifications for lymph node (LN) staging have recently been proposed to improve upon the UICC/AJCC N category staging convention. Ratio-based systems and logarithmic odds (LODDS) scores are two families of novel competing staging systems. We compared UICC/AJCC staging with 5 ratio and LODDS systems in predicting overall survival (OS) in patients with resected gastric cancer. METHODS: Using a large population-based dataset, we identified 12,184 nonmetastatic resectable gastric cancer patients between 1988 and 2004. We compared each subject's UICC/AJCC N stage with five novel staging schemes. We analyzed the OS for each method. Our comparison metric was the log-rank Chi squared statistic; larger Chi squared statistics indicate improvements in N stage discrimination. RESULTS: Median OS was 2.1 years (95 % CI 2.0-2.2 years), while median patient follow-up for surviving patients was 8.3 years (range, 1 month-22 years). Although all 5 staging systems were either comparable or superior to the UICC/AJCC convention, a LN ratio method outperformed others in N stage discrimination based on log-rank tests for OS. This trend was independent of the number of LNs examined. CONCLUSIONS: Novel LN staging methods have a higher degree of discrimination utility than the UICC/AJCC N convention. These methods may have a role in reducing the prognostic impact of LN count variability. Of the systems assessed, the LN ratio system that assigns greater risk attribution to cases with <16 LNs was the best classification method to predict OS in patients with resectable gastric cancer. PMID- 24242678 TI - MicroRNAs with prognostic potential for metastasis in clear cell renal cell carcinoma: a comparison of primary tumors and distant metastases. AB - BACKGROUND: MicroRNAs (miRNAs) are regulators of gene expression in tumor development and progression. However, their influence on metastasis of clear cell renal cell carcinoma (ccRCC) is less understood. To determine the role of miRNAs in metastatic progression, miRNA expression in primary ccRCC was compared to distant metastases. METHODS: Total RNA of 53 primary ccRCCs, 35 distant metastases from lung, bone, brain, and abdomen, as well as 17 normal kidney tissues was isolated from fresh frozen tissue and formalin-fixed paraffin embedded (FFPE) samples. The miRNA microarrays were performed based on fresh frozen tissue. Results were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on fresh frozen tissue and FFPE samples. Real time cell analyses and transwell invasion assays were carried out after transient transfection of microRNA-30c (miR-30c) in cell line 786-O. RESULTS: There were 14 miRNAs differently expressed in metastatic primary ccRCC and distant metastases compared to non-metastatic primary tumors. A strong correlation of miRNAs to progression-free- and cancer-specific 5-year-survival was determined. Specific miRNAs were differently expressed in distant metastases compared to primary ccRCC. A miRNA signature distinguished lung metastases from other metastatic sites. Overexpression of miR-30c increased adherence and decreased migration and invasion in the ccRCC cell line. CONCLUSIONS: MiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection. PMID- 24242679 TI - Association of a genetic variant of CYP19A1 with multicentric development of lung adenocarcinomas. AB - BACKGROUND: The detection rate of multiple lung adenocarcinomas, which display multiple ground glass opacity nodules in the peripheral lung, is increasing because of advances in high resolution computed tomography. The genetic backgrounds of multiple nodules and the mechanisms that underlie their multicentric development are unknown. In this study, we examined single nucleotide polymorphisms (SNPs) of the cytochrome P450 19A1 gene to determine if they are associated with multiple adenocarcinomas risk. METHODS: Fifty-one cases of multiple adenocarcinomas with lepidic growth, 62 cases of a single adenocarcinoma with lepidic growth, and 126 control cases were analyzed. Three SNPs were analyzed by using a 5' nuclease assay with TaqMan minor-groove-binder probe. The expression level of CYP19A1 in the noncancerous lung was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: A minor allele of SNP rs3764221, which is located in the CYP19A1 gene, was significantly associated with multiple adenocarcinomas risk (adjusted odds ratio = 3.06; P = 0.006). Other polymorphisms of CYP19A1 were not significantly associated with the risk of multiple adenocarcinomas. A minor allele of SNP rs3764221 was also associated with a higher level of CYP19A1 messenger RNA expression (P = 0.03). CONCLUSIONS: SNP rs3764221 contributes to the development of multicentric adenocarcinomas in the peripheral lung by causing higher levels of CYP19A1 expression. PMID- 24242680 TI - Morbidity associated with colostomy reversal after cytoreductive surgery and HIPEC. AB - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival in selected colorectal cancer patients with peritoneal metastases. In these patients, the risk of a low anastomosis is sometimes diminished through the creation of a colostomy. Currently, the morbidity and mortality associated with the reversal of the colostomy in this population is unknown. METHODS: Our study involved two prospectively collected databases including all patients who underwent CRS-HIPEC. We identified all consecutive patients who had a colostomy and requested a reversal. The associations between four clinical and ten treatment-related factors with the outcome of the reversal procedure were determined by univariate analysis. RESULTS: 21 of 336 patients (6.3 %) with a stoma with a mean age of 50.8 (standard deviation 10.2) years underwent a reversal procedure. One patient was classified as American Society of Anesthesiologists (ASA) grade III, 6 as ASA grade II, and the remaining as ASA grade I. Median time elapsed between HIPEC and reversal was 394 days (range 133-1194 days). No life-threatening complications or mortality were observed after reversal. The reversal-related morbidity was 67 %. Infectious complications were observed in 7 patients (33 %). Infectious complications after HIPEC were negatively correlated with the ultimate restoration of bowel continuity (P = 0.05). Bowel continuity was successfully restored in 71 % of the patients. CONCLUSIONS: Although the restoration of bowel continuity after CRS-HIPEC was successful in most patients, a relatively high complication rate was observed. Patients with infectious complications after HIPEC have a diminished chance of successful restoration of bowel continuity. PMID- 24242681 TI - High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. AB - PURPOSE: Glucose transporter type 1 (Glut1) plays a crucial role in cancer specific metabolism to adapt to the rapid growth and tumor microenvironment in diverse malignant tumors. This study examined the clinical, pathological, and prognostic features of Glut1 expression on primary lesions of esophageal squamous cell carcinoma. METHODS: Immunohistochemical staining of Glut1 and CD34 was performed using paraffin-embedded sections of tissues obtained from 145 resectable esophageal squamous cell carcinoma patients without preoperative treatment. Microvessel density was calculated from CD34 staining. RESULTS: Glut1 positivity was observed in 41 patients (28.2 %) and associated with depth of invasion [odds ratio (OR) 2.984; 95 % confidence interval (CI) 1.208-7.371; P = 0.018] and vascular invasion (OR 2.771; 95 % CI 1.118-6.871; P = 0.028) in multivariate analysis. Glut1 positivity was a significant disadvantage to both relapse-free survival [hazard ratio (HR) 2.021; 95 % CI 1.100-3.712; P = 0.023] and esophageal cancer-specific survival (HR 2.223; 95 % CI 1.121-4.411; P = 0.022) in univariate Cox hazard analysis, but was not independently associated with relapse-free survival or cancer-specific survival in multivariate analysis. The relationship between Glut1 expression and first relapse site was investigated. Glut1 positivity was not associated with lymph node recurrence (HR 1.009; 95 % CI 0.402-2.530; P = 0.985) but was significantly associated with hematogenous recurrence (HR 3.701; 95 % CI 1.655-8.273; P = 0.001) in univariate Cox hazard analysis. Microvessel density was calculated to evaluate angiogenesis, and it was observed that Glut1 positivity was significantly associated with high microvessel density (P < 0.001). CONCLUSIONS: Glut1 expression was associated with hematogenous recurrence. The findings provide evidence of the significance of Glut1 expression as a biomarker. PMID- 24242683 TI - Atherosclerotic biomarkers and aortic atherosclerosis by cardiovascular magnetic resonance imaging in the Framingham Heart Study. AB - BACKGROUND: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. METHODS AND RESULTS: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). CONCLUSIONS: In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors. PMID- 24242685 TI - White matter abnormalities in adolescents with major depressive disorder. AB - The purpose of this study was to identify areas of abnormal white matter microstructure in adolescents with Major Depressive Disorder (MDD) using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values representing preferential diffusivity along major tracts were examined using tract-based spatial statistics across the whole brain in adolescents ages 13-19 with MDD (n = 31) compared with demographically-matched healthy controls (n = 31). We not only examined frontal lobe tracts that have been most frequently identified as abnormal in previous DTI studies of older depressed patients, but also tested for FA group differences across the whole brain to determine if adolescent depression was related to any other regional white matter abnormality. MDD-diagnosed adolescents had significantly lower FA in many regions concentrated predominantly in the frontal lobe. There also was strong evidence for lower FA in bilateral anterior/posterior limbs of the internal capsules, as well as tracts through the midbrain, left external capsule, right thalamic radiation and left inferior longitudinal fasciculus. Consistent with previous findings in depressed young and elderly adults, the current study found evidence for abnormal microstructure in white matter connections of the frontal lobe in MDD adolescents. There also was strong evidence for FA abnormalities in corpus callosum genu, internal and external capsule tracts, thalamus and midbrain, notable for both the relative magnitude of these effects and absence from most previous white matter studies of depression. These abnormalities might represent important markers of early life onset depression. PMID- 24242682 TI - Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. PMID- 24242684 TI - Factor II activity is similarly increased in patients with elevated apolipoprotein CIII and in carriers of the factor II 20210A allele. AB - BACKGROUND: Few studies have so far investigated the relationship between apolipoprotein CIII (Apo CIII) and coagulation pathway in subjects with or without coronary artery disease (CAD). METHODS AND RESULTS: Serum Apo CIII concentrations and plasma coagulant activities of factor II (FII:c), factor V (FV:c), and factor VIII (FVIII:c), and activated factor VII (FVIIa) were analyzed in a total of 933 subjects, with (n=687) or without (n=246) angiographically demonstrated CAD and not taking anticoagulant drugs. Activated factor X (FXa) generation assay was performed on plasma from subgroups of subjects with low and high levels of Apo CIII. A statistical incremental concentration of FII:c, FV:c, and FVIIa levels was observed through the quartiles of Apo CIII distribution in the population considered as a whole. Significant results were confirmed for FII:c in CAD and CAD-free subgroup when separately considered. Subjects within the highest Apo CIII quartile (>12.6 mg/dL) had high FII:c levels not statistically different from those of carriers of 20210A allele (n=40; 4.28%). In a multiple linear model, Apo CIII was the best predictor of FII:c variability, after adjustment for age, gender, plasma lipids, CRP, creatinine, diagnosis, and carriership of 20210A allele. FXa generation was increased and its lag time shortened in plasmas with high Apo CIII levels. However, after thrombin inhibition by hirudin, differences between low and high Apo C-III samples disappeared. CONCLUSIONS: Elevated concentrations of Apo CIII are associated with an increase of thrombin activity to an extent comparable with the carriership of G20210A gene variant and mainly modulating the thrombin generation. PMID- 24242686 TI - Investigation of matrix-induced interferences in mixed-gas helium-argon inductively coupled plasma mass spectrometry. AB - The effects of various matrix constituents, Cd, Co, Pb, and synthetic ocean water, on analyte ion signal were investigated in He-Ar plasma source mass spectrometry. Analyte ion signal suppressions and enhancements were observed in the presence of varying concomitants. The method used for optimizing analyte ion lens signal determined whether suppression or enhancement was encountered. Tuning on a nitric acid standard solution results in a suppressed signal, whereas tuning on the analyte in the presence of the matrix results in signal enhancement, relative to that obtained with no concomitant present. The heavier mass lead concomitant had the greatest effect on the ion signal. Additionally, lighter analyte elements were affected to a greater extent than heavier analytes in the presence of high concomitant concentrations. PMID- 24242687 TI - A wide-angle secondary ion probe for organic ion imaging. AB - A secondary ion source has been developed for an organic ion microprobe capable of imaging samples up to 2 em in diameter. The source uses a focused 5 keY Cs(+) ion beam which is rastered across the sample surface, and secondary ions from each point on the sample are collected and formed into a low energy beam to be analyzed by a quadrupole mass filter. Dynamic emittance matching is employed to deflect ions from off-axis points on the sample back onto the mass analyzer axis. Rastering and dynamic emittance matching are rapidly controlled by assembly language programs using an IBM/AT (80286) type computer. A low energy ion monitor was used to tune and evaluate the secondary ion source by providing a magnified cross-sectional image of the ion beam at the source exit aperture. A well-focused and centered secondary ion beam was obtained from each point on the sample, indicating that large-scale dynamic emittance matching with high collection efficiency is possible. Mass resolved images of grids and glycerol samples are shown to demonstrate the performance of the integrated secondary ion source mass analyzer and control system. PMID- 24242688 TI - Kinetic and spectroscopic characterization of the isomers of the allyl bromide molecular ion. AB - The kinetics of the ion/molecule reactions of the molecular ion of allyl bromide (3-bromopropene), C3H5Br(+)., with its neutral show that only (82 +/- 2)% of these ions are reactive. This percentage is mildly sensitive to ionization energy below 13 eV, but is pressure insensitive. The collisionless infrared multiphoton induced photofragmentation of these ions at 10.25 MUm and at variable power densities is consistent with the presence of two ionic species in the ratio obtained from the kinetic experiments. The most abundant species undergoes much faster photofragmentation at this wavelength, but at 10.59 MUm the photofragmentation rates become comparable. Experiments performed by isolating the remaining molecular ions after completion of the ion/molecule reaction confirm that the unreactive species corresponds to the slow photodissociating ion at 10.25 MUm. A combination of kinetic experiments and photodissociation is used to establish that the less abundant species behaves unlike the molecular ion obtained from 1-bromopropene, 2-bromopropene, or bromocyclopropane. The two structures for the molecular ion are shown to originate from ionization and not by isomerization through collisions. PMID- 24242689 TI - Fragmentation analysis of bradykinin by (252)cf-plasma desorption mass spectrometry. AB - The (252)Cf-plasma desorption (PO) mass spectrum of the nonapeptide bradykinin was studied in detail with particular emphasis on the fragmentation pattern resulting from fast metastable decay of the molecular ion. N-acetyl and O-methyl derivatives of bradykinin were used as mass shift species for assignment of N terminal and C-terminal fragment ions. Thirty-seven sequence-specific fragment ions were identified, including those that are due to cleavage of peptide backbone as well as side chain bonds (i.e., dn, vn, wn fragment ions). The degree of fragmentation correlates with what has been observed by fast atom bombardment tandem mass spectrometry using hi~h energy collisional activation. The high degree of excitation of bradykinin molecules in (252)Cf-POMS is undoubtedly due to the special nature of excitation intrinsic to the (252)Cf_PD process where electronic excitation occurs with a very high probability due to the high electron and photon flux surrounding the nuclear fission fragment track.These results offer further evidence that (252)Cf_PDMS, in addition to providing molecular weight information, can be used to sequence peptides without the need for a second stage of molecular excitation. PMID- 24242690 TI - High Accuracy Molecular Weight Determination and Variation Characterization of Proteins Up To 80 ku by Ionspray Mass Spectrometry. AB - A quadrupole mass spectrometer with an ionspray interface was used to measure the molecular weight (MW) of proteins up to 80,000 u . With the improvements in instrument cahbration by a statistical averaging method and in data analysis by a gaussian curve-fitting method, precision of MW determination as high as 12 ppm was achieved with equine myoglobin (MW 16,950.4 +/- 0.2 u). Exact MW determination of three components in cerato-ulmin revealed that the two minor ones had lost amino acid residues Ser and Ser-Asp, respectively, from the major component (MW 7618.4 +/- 0.2 u). MW classifIcation of eight components in the Fab fragment of a monoclonal antibody revealed that one set of four had MW - 47,540 u and the other - 47,640 u. The MW difference of 100.2 +/- 0.6 u between fragment 1 and 2, attributed to inhomogeneous cleavage at the Fab C-terminus, was probably due to one additional Thr in 1. The MW of bovine serum albumin (BSA) was found to be 66,431.5 +/- 1.3 u, - 164 u higher than the calculated sequence MW, most probably because of the incorrectness in the previously reported BSA amino acid sequence. The MW of human serum transferrin (79,556.8 +/- 1.7 u) was shown to be 4414 u higher than the sequence MW, pointing to a glycosylation of 22.7 sugar units in this protein. The greater complexity in bovine serum transferrin (MW 78,030.5 +/- 1.8 and 78,326 +/- 3.3 u for the two major components) was correlated with the heterogeneity in the glycosylation. PMID- 24242691 TI - Structural Characterization of Normal and Modified Oligonucleotides by Matrix assisted Laser Desorption Fourier Transform Mass Spectrometry. AB - Matrix-assisted UV laser desorption Fourier transform mass spectrometry (266 nm, nicotinic acid matrix) can be used for the detailed structural characterization of normal and modified oligonucleotides. The negative ion spectra for these compounds revealed abundant (M - H) (-) ions as well as fragment ions that provided the information necessary to determine oligomer sequence and to differentiate isomers. The nicotinic acid matrix was required for the production of (M - H) (-) ions for the oligonucleotide dimers, trimers, tetramers, and hexamers examined in this study. Elimination of the nicotinic acid matrix resulted in complete loss of the (M -H) (-) ions as well as most of the larger fragment ions for the oligomers. The primary fragmentation pathway was observed to be phosphate ester bond cleavage with the resulting charge retained on the 3' end of the oligomer and enabled isomeric differentiation of compounds such as d(S'-CGCG-3') and d(S'-CCGG-3'). Collisioninduced dissociation experiments of the (M - H) (-) ions for these compounds confirmed the preferential loss of nucleotides from the 5' end of the oligomers. The presence and location of modifications such as methyl and ethyl alkyl groups to the oligonucleotides could also be identified. PMID- 24242692 TI - Spin-trapped Radicals: Determination by LC-TSP-MS and LC-ESI-MS. AB - The 4-POBN[alpha-(4-pyridyl-l-oxide)-N-tert-butyl-nitrone] radical adducts of ethyl and pentyl radicals were determined by a combination of high performance liquid chromatography (HPLC) combined with electron paramagnetic resonance (EPR) with HPLC-electrospray (ESI)-mass spectrometry and HPLC-thermospray (TSP)-MS. The identifIcation of the peak corresponding to the spin-trapped radical was done by performing HPLC-EPR under the same chromatographic conditions as the HPLC-MS. The radical adducts could be determined by both techniques, even though for ESI only 12 MUL/min of the total 1 mL/min HPLC flow rate could be directed into the ion source. PMID- 24242693 TI - Multispectral identiftcation of alkyl and chloroalkyl phosphates from an industrial effluent. AB - Multispectral techniques (gas chromatography combined with low and high resolution electron-impact mass spectrometry, low and high resolution chemical ionization mass spectrometry, and Fourier transform infrared spectroscopy) were used to identify 13 alkyl and chloroalkyl phosphates in a water sample taken from the effluent of a plant that manufactures fire-retardant chemicals. Of the 13 phosphates identified, only 4 were located in hbrary mass spectral data bases; thus, techniques other than conventional low resolution electron-impact mass spectrometry with data base matching were required. Several of the Identified phosphates are commonly used ftre retardants; however, three exhibited chemical structures different from those of the commercially manufactured fire retardants and the reactants used in their synthesis. PMID- 24242694 TI - Internal standard correction of results obtained by atmospheric pressure chemical ionization mass spectrometry. AB - An internal standard system has been developed for a mass spectrometer equipped with an atmospheric pressure chemical ionization source. The system has been used to overcome sensitivity drift problems that are commonly encountered when the spectrometer is used for long-term environmental monitoring. Additionally, the internal standard has been used to correct sensitivity changes induced by the matrix being analyzed. Principal components of the system are a low concentration internal standard source and a flow-delivery system for introducing the standard to the reagent gas delivery stream of the spectrometer. Following an experiment, real-time data are downloaded to a personal computer where internal standard correction and data analysis are performed. Application of the internal standard to the measurement of nicotine and pyridine is demonstrated. PMID- 24242695 TI - An enlarged data base of electron-ionization mass spectra. AB - The computer-searchable data base of reference mass spectra described earlier has been increased in size by 76%, so that it now contains 139,859 different spectra of 118,144 different compounds. The average number of peaks per spectrum is 53. All spectra were examined for errors by the Probability Based Matching (PBM) and the Quality Index (QI) algorithms and by human inspection. An improvement to the QI algorithm is based on the Terwilliger suggestion concerning saturated spectra. The number of different elemental compositions of compounds has increased by 64%. By using unknowns from the original data base with PBM, the probability that these incorrectly match a new spectrum is only 33% of that of incorrectly matching a spectrum in the original data base, further demonstrating that the variety of data in the library has been substantially expanded. Including additional reference spectra (measured under different conditions) of the same compound in the data base reduced the proportion of incorrect best-matching spectra by 42%. PMID- 24242696 TI - Comparative evaluations of mass spectral data bases. AB - Recent reports from the National Institute of Science and Technology (NIST) state that its large (53,994) collection of mass spectra is unique in "consisting almost entirely of complete spectra." Our study of the 1989 Registry of Mass Spectral Data of 139,859 different spectra shows that its 53,994 spectra containing the most peaks average 108 peaks per spectrum, 48% larger than the NIST data base. Further, in matching unknown spectra of compounds present in both files, by using criteria yielding 68% reliability, 14% of the possible correct answers were recalled with the NIST data base versus 36% with the Registry. PMID- 24242697 TI - Comparative evaluations of mass spectral databases. AB - This Communication presents a statistical analysis of the distributions of the National Institute of Standards and Technology/Environmental Protection Agencyj Mass Spectrometry Data Center Mass Spectral Database and the Wiley Registry of Mass Spectra according to sizes (peaks per spectrum) of spectra. The differences in the distributions are explained in terms of the different philosophies under which the two databases were built. The Wiley Registry is a collection that attempts to include all available spectra, including spectra of unique compounds derived from the literature. The NIST collection selects primarily spectra of interest for chemical analysis. PMID- 24242699 TI - TTF-1 expressing sellar neoplasm with ependymal rosettes and oncocytic change: mixed ependymal and oncocytic variant pituicytoma. PMID- 24242700 TI - Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders. AB - Metallothionein-3 (MT-3) is an intracellular, low molecular weight protein mainly distributed in the central nervous system but also in various peripheral organs and several types of human neoplasms. However, details of MT-3 expression have not been examined in human adrenal cortex and its disorders. The mRNA levels of MT-3 were first evaluated by quantitative RT-PCR (qPCR) in adrenocortical aldosterone-producing adenoma (APA: 11) and cortisol-producing adenoma (CPA: 14). In addition, MT-3 immunohistochemistry was performed in non-pathological adrenal glands (NA: 19), idiopathic hyperaldosteronism (IHA: 10), APA (20), CPA (24), adjacent non-neoplastic adrenal glands of adenoma (AAG: 20), and adrenocortical carcinoma (ACC: 8). H295R cells were also treated with angiotensin-II or forskolin in a time-dependent manner, and the changes of MT-3 mRNA levels were evaluated by qPCR. Results of qPCR analysis demonstrated that MT-3 mRNA levels were significantly higher in APA than CPA (P = 0.0004). MT-3 immunoreactivity was detected in the zona glomerulosa of NA, IHA, and AAG, as well as in APA, CPA, and ACC. When treated with angiotensin-II and forskolin, MT-3 mRNA levels reached a peak by 12 h in H295R cells, with significantly higher levels compared to control non-treated cells (P < 0.01). The presence of MT-3 in the ZG of NA, IHA, and AAG, as well as APA may imply a role in the pathophysiology of aldosterone-producing tissues. PMID- 24242701 TI - Competing risks analysis in mortality estimation for breast cancer patients from independent risk groups. AB - This study quantifies breast cancer mortality in the presence of competing risks for complex patients. Breast cancer behaves differently in different patient populations, which can have significant implications for patient survival; hence these differences must be considered when making screening and treatment decisions. Mortality estimation for breast cancer patients has been a significant research question. Accurate estimation is critical for clinical decision making, including recommendations. In this study, a competing risks framework is built to analyze the effect of patient risk factors and cancer characteristics on breast cancer and other cause mortality. To estimate mortality probabilities from breast cancer and other causes as a function of not only the patient's age or race but also biomarkers for estrogen and progesterone receptor status, a nonparametric cumulative incidence function is formulated using data from the community-based Carolina Mammography Registry. Based on the log(-log) transformation, confidence intervals are constructed for mortality estimates over time. To compare mortality probabilities in two independent risk groups at a given time, a method with improved power is formulated using the log(-log) transformation. PMID- 24242702 TI - Snoring and carotid artery intima-media thickness. AB - OBJECTIVES/HYPOTHESIS: A growing body of evidence indicates that primary snoring (PS) may be the initial presentation of sleep-disordered breathing and can adversely affect an individual's health. Individuals with the sole diagnosis of PS were evaluated to determine if a relationship exists between snoring and thickening of the intima media of the carotid arteries. STUDY DESIGN: Cross sectional study. METHODS: Our institution's sleep center database identified patients aged 18 to 50 years who had a diagnostic sleep study with apnea-hypopnea index <5 between December 2006 and January 2012. Subjects underwent a diagnostic carotid artery duplex ultrasound measuring the intima-media thickness (IMT) of the bilateral carotid arteries at four separate points. A validated Snoring Outcomes Survey (SOS) was completed and used to categorize snorers and nonsnorers. Groups were compared using a Student t test. RESULTS: Of 913 patients who met inclusion criteria, 54 patients completed both the carotid duplex ultrasound and SOS. There were no statistically significant differences in IMT for the groups defined by smoking or diabetes. Compared to nonsnorers, snorers were found to have a significantly greater IMT at two points along the left internal carotid artery and one point on the right side. When considering all eight points, IMT was significantly greater in snorers. CONCLUSIONS: This study shows a relationship between PS and IMT of the carotid arteries. Given the well described relationship between increased carotid IMT and serious health conditions, nonapneic snoring may be a precursor to changes of the carotid artery intima and should be further investigated. LEVEL OF EVIDENCE: 3b. PMID- 24242703 TI - B7-H6 protein expression has no prognostic significance in human gastric carcinoma. AB - B7-H6, a novel member of the B7 family which binds to NKp30 to trigger antitumor NK cell cytotoxicity and cytokine secretion. Recently, B7-H family has been reported to be a negative regulator of the immune response in patients with gastric carcinoma. However, no reports have investigated the clinical significance of B7-H6 expression in human gastric cancer. We present the first study to the clinicopathological and prognostic value of B7-H6 in primary gastric tumors and adjacent non-tumor tissues at the protein level. Here we show that B7 H6 immunoreactivity was expressed in 6/60 (10%) gastric tumors and 8/43 (18.60%) adjacent non-tumor tissues. No statistical difference was found between B7-H6 expression and various prognostic factors; however, B7-H6-positive carcinomas were significantly associated with a higher differentiation (p = 0.047). The survival analysis did not confirm the prognostic significance of B7-H6 expression in gastric cancer patients. Our data suggest that B7-H6, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer. PMID- 24242704 TI - Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds. AB - BACKGROUND: Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30 day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases. OBJECTIVES: To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA. SEARCH METHODS: We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013). SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials, and extracted data from the trial reports. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and planned to calculate the mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both fixed-effect and random-effects models. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below.1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people).2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people).3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people). AUTHORS' CONCLUSIONS: We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary. PMID- 24242706 TI - Caval valve implantation for treatment of tricuspid regurgitation: post-mortem evaluation after mid-term follow-up. PMID- 24242705 TI - Prostate cancer derived prostatic acid phosphatase promotes an osteoblastic response in the bone microenvironment. AB - Approximately 90 % of patients who die of prostate cancer (PCa) have bone metastases, often promoting osteoblastic lesions. We observed that 88 % of castration-resistant PCa (CRPC) bone metastases express prostatic acid phosphatase (PAP), a soluble secreted protein expressed by prostate epithelial cells in predominately osteoblastic (n = 18) or osteolytic (n = 15) lesions. Additionally, conditioned media (CM) of an osteoblastic PCa xenograft LuCaP 23.1 contained significant levels of PAP and promoted mineralization in mouse and human calvaria-derived cells (MC3T3-E1 and HCO). To demonstrate that PAP promotes mineralization, we stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. Furthermore, the mineralization promoted by LuCaP 23.1 CM was also blocked by phosphonic acid, suggesting PAP is responsible for the mineralization promoting activity of LuCaP 23.1. In addition, gene expression arrays comparing osteoblastic to osteolytic CRPC (n = 14) identified betacellulin (BTC) as a gene upregulated during the osteoblastic response in osteoblasts during new bone formation. Moreover, BTC levels were increased in bone marrow stromal cells in response to LuCaP 23.1 CM in vitro. Because new bone formation does occur in osteoblastic and can occur in osteolytic CRPC bone metastases, we confirmed by immunohistochemistry (n = 36) that BTC was highly expressed in osteoblasts involved in new bone formation occurring in both osteoblastic and osteolytic sites. These studies suggest a role for PAP in promoting the osteoblastic reaction in CRPC bone metastases and identify BTC as a novel downstream protein expressed in osteoblasts during new bone formation. PMID- 24242707 TI - Vanishing pulmonary oedema, a visual delight! PMID- 24242709 TI - Quantification of cantharidin in canthariphilous ceratopogonidae (Diptera), anthomyiidae (Diptera) and cantharidin-producing oedemeridae (Coleoptera). AB - Cantharidin contents were determined in several canthariphilous insects by means of quantitative gas chromatography. Usually the ceratopogonidsAtrichopogon oedemerarum andA. trifasciatus caught in the field contained low concentrations of cantharidin, with concentrations in males, in most cases, being lower than in females. When fed in the laboratory with synthetic cantharidin, these species concentrated cantharidin by as much as 100-fold (males) and 40-fold (females). Accumulation in the different body tagmata (head, thorax, abdomen) of these species is similar. Maximal concentrations of cantharidin in tissues ofAtrichopogon are comparable to those known from oedemerid and meloid beetles. InA. trifasciatus about 90% of total cantharidin content is bound in tissues. Investigations using the canthariphilous anthomyiid flyAnthomyia pluvialis and three cantharidin-producing oedemerid species revealed the same pattern of distribution in different body tagmata as inAtrichopogon. PMID- 24242708 TI - Vitamin D receptor agonist EB1089 is a potent regulator of prostatic "intracrine" metabolism. AB - BACKGROUND: A contributing factor to the emergence of castrate resistant prostate cancer (CRPC) is the ability of the tumor to circumvent low circulating levels of testosterone during androgen deprivation therapy (ADT), through the production of "intracrine" tumoral androgens from precursors including cholesterol and dehydroepiandrosterone (DHEA). As these processes promote AR signaling and prostate cancer progression their modulation is required for disease prevention and treatment. METHODS: We evaluated the involvement of the vitamin D receptor ligand EB1089 in the regulation of genes with a role in androgen metabolism using the androgen dependent cell lines LNCaP and LAPC-4. EB1089 regulation of androgen metabolism was assessed using QRT-PCR, luciferase promoter assays, western blotting, enzyme activity assays, and LC-MS analyses. RESULTS: EB1089 induced significant expression of genes involved in androgen metabolism in prostate cancer cells. Real-Time PCR analysis revealed that VDR mediated significant regulation of CYP3A4, CYP3A5, CYP3A43, AKR1C1-3, UGT2B15/17, and HSD17B2. Data revealed potent regulation of CYP3A4 at the level of mRNA, protein expression and enzymatic activity, with VDR identified as the predominant regulator. Inhibition of CYP3A activity using the specific inhibitor ritonavir resulted in alleviation of the anti-proliferative response of VDR ligands in prostate cancer cells. Mass spectrometry revealed that overexpression of CYP3A protein in prostate cancer cells resulted in a significant increase in the oxidative inactivation of testosterone and DHEA to their 6-beta-hydroxy-testosterone and 16-alpha-hydroxy DHEA metabolites, respectively. CONCLUSIONS: These data highlight a potential application of VDR-based therapies for the reduction of growth-promoting androgens within the tumor micro-environment. PMID- 24242710 TI - Olea europaea chemicals repellent toDacus oleae females. AB - The egg dispersion strategy of the olive fruit flyDacus oleae, which is dependent on chemicals from the fruit, was investigated. In particular, the exact role ofo diphenolic compounds, such as the typical olive glucosides, oleuropein and demethyloleuropein, and their derivatives was clarified. It appears that the strong chemotactile repulsive effect exerted by the water fraction of crushed olives is due mainly to (E)-2-hexenal. Several compounds, such asbeta-3,4 dihydroxyphenylethanol and other oleuropein derivatives, which exert a strong chemotactile repulsion, were newly identified or confirmed either in fresh olive juice or in olive mill waste water. This result confirms that the small droplets of olive juice, regurgitated just after egg laying by theD. oleae female all around the oviposition hole, actually prevent other females from ovipositing on the same fruit. PMID- 24242711 TI - Absorption and release of pheromone ofEpiphyas postvittana (Lepidoptera: Tortricidae) by apple leaves. AB - The absorption and release of the pheromone ofEpiphyas postvititana (Lepidoptera: Tortricidae),E 11-14: OAc andE,E 9, 11-14: OAc (95:5) by apple leaves was studied using electroantennograms (EAG) and sticky traps baited with pheromone-treated leaves. Leaves exposed to an airstream containing pheromone reached a constant level of pheromone release within 3 min. Release occurred over a period greater than 24 hr, following removal of leaves from the pheromone-saturated environment. Pheromone-treated leaves were effective as lures in sticky traps for at least three nights, although the average catch per night decrease logarithmically with time. In the field, pheromone was detected by EAG on leaves harvested from up to 25 cm away from a central point source of pheromone. The shape of a surface representing equal pheromone re-release from leaves around a central point source was defined by interpolation from a three-dimensional transect. Leaves harvested from 5 cm under the dispensers showed the highest pheromone release rate. Leaves downwind of the dispensers also had higher release of pheromone. In a treated orchard, significantly higher EAG measurements were recorded in the rows of trees that contained dispensers, compared to grass interrows or untreated trees. The implications of foliar pheromone adsorption and release on atmospheric concentrations and insect behavior require further investigation. PMID- 24242712 TI - Scent, sex, and the self-calibrating rat. AB - We propose that one mechanism whereby male rats,Rattus norvegicus, might gauge the reproductive condition of a female is by calibrating a stable odor with an odor that fluctuates through her reproductive cycle. We provide behavioral and histological evidence in support of such a self-calibration model. Male rats sniffed frequently at various body zones of females, and the proportion of sniffs deployed to each zone varied with the females' reproductive condition and relatedness. The females' haunches received more sniffs than any other part of their bodies, irrespective of their relatedness or reproductive condition. Furthermore, males tended to sniff the haunch after sniffing the forequarters, as part of a sequence of sniffing along a female from forequarters to hindquarters. Histology of the skin sebaceous glands indicated that the secretory activity of glands in the haunch, but not those in the forequarters, changed during estrus. Therefore, male rats had the opportunity to judge a female's reproductive status by calibrating the odor of her haunch against that of her forequarters. Self calibration could represent a means of accommodating differences in odor within individuals. PMID- 24242713 TI - Analysis of rat haunch odor using dynamic solvent effect and principal component analysis. AB - We used the dynamic solvent effect to sample rat haunch odor, which we then analyzed using principal component analysis. PCA, based on 22 volatile components, indicated that one axis clearly separated rat haunch odor samples according to sex and female reproductive condition (estrus and diestrus), explaining 79.5% of the variation in proportional peak area. We have therefore been able to separate odors along biologically meaningful lines. PMID- 24242714 TI - To penetrate or not to penetrate? A behavioral choice by bean beetle first-instar larvae in response toPhaseolus vulgaris seed surface quality. AB - Survival ofAcanthoscelides obtectus larvae depends on the ability of the first instar to pierce the seed coat ofPhaseolus vulgaris, which represents a critical sequence because of physical characteristics and toxicity. We have investigated the influence of seed surface quality on larval boring behavior by the usual method of surface washing with different solvents, or by removing the testa, or by coating the testa with a polymer spray. Observations were made on isolated larvae in no-choice and dual-choice bioassays. In the no-choice situation, larval penetration was reduced after seed coats were soaked with chloroform, whereas water, diethyl ether, or methanol had no significant effect. The ratio of boring attempts to successful penetrations was increased on seeds washed with chloroform. In the dual-choice situation, larvae avoided artificially coated seeds and preferred untreated seeds over those washed with chloroform or methanol. These results indicate that boring stimulants exist on the seed coat and that they are removed by chloroform and methanol or made inaccessible by artificial coating. The high mortality of first instars on seeds washed with these two solvents is attributed to a lack of chemicals necessary to initiate and sustain boring behavior, causing larval stress, possibly due to prolonged locomotory activity and starvation. Thus, seed coat quality may influence the population dynamics ofA. obtectus. PMID- 24242715 TI - Prior anesthesia impairs a chemically mediated fright response in a gobiid fish. AB - Quinaldine and phenoxyethanol, two commonly used fish anesthetics, reduced the intensity of a chemically induced fright response in a marine goby. MS-222, an anesthetic that has been indicated as harmful to fish olfaction, had no significant effect. Understanding these effects must await further study, but it is clear that caution should be exercised. One should definitely not use quinaldine or phenoxyethanol instead of MS-222 in an effort to avoid harmful effects. PMID- 24242716 TI - Seed germination and growth inhibitory cadinenes fromEupatorium adenophorum spreng. AB - Chloroform extract of the aerial parts ofEupatorium adenophorum Spreng was fractionated and examined for growth inhibition. Bioassay-directed fractions of the plant materials afforded three known cadinenes and beta-sitosterol. The effects of different fractions as well as isolated cadinenes were determined usingAllium cepa, Raphanus sativus, andCucumis sativus seeds. Three-day exposure to these cadinenes significantly inhibited germination and seedling growth of all three assay seeds. The degree of inhibition was dependent upon seed species and the concentrations of the compounds tested. Cadinene(1) was found to be more inhibitory to the seeds tested and the activity of the cadinene(3) was less than that of(1) and(4). PMID- 24242717 TI - Comparison of larval and adult P-450 activity levels for alkaloid metabolism in desertDrosophila. AB - The cytochrome P-450 monooxygenase system has been implicated in plant utilization by at least three species ofDrosophila (D. nigrospiracula, D. mettleri, andD. mojavensis) that are endemic to the Sonoran Desert of the southwestern United States and northwestern Mexico. Basal and induced levels of total cytochrome P-450 were determined for third-instar and decapitated 2- to 5 day post eclosion adults of the three desert species. Total P-450 levels, both basal and induced for all species assayed, were significantly higher for adults than for larvae by up to 20-fold. On a per organism basis, the levels of in vitro metabolism of the cactus alkaloid, carnegine, and patterns of response to induction by cactus tissue for adult desertDrosophila approximated those of larvae. Induction by phenobarbital, however, resulted in levels of in vitro carnegine metabolism that were up to 5.6-fold higher in adults than in larvae. PMID- 24242718 TI - Surface disposition and stability of pest-interactive, trichome-exuded diterpenes and sucrose esters of tobacco. AB - The precise physical location of trichome-exudate biochemicals on the plant surface is undoubtedly important in plant-pest interactions, perhaps particularly those involving fungal and bacterial pathogens that invade the plant through the epidermal layer. The chemical stability of exuded compounds is also important in this regard. Here we have studied these two aspects of trichome biology using the highly exuded tobacco line,Nicotiana tabacum, T.I. 1068. Particularly under high relative humidity growth conditions, sucrose esters (SE) were found to migrate from the exudate droplet around the gland down the trichome stalk to the epidermal cells below. Six days after labeling leaf midveins on plants grown in a high humidity environment, 29 and 71% of label found in SE were recovered with trichome glands and below gland regions, respectively. Corresponding disposition in the moderate humidity environment was 40 and 60%, respectively. Migration of less polar duvatrienediols (DVT) was less marked. Staining of SE with rhodamine B showed the occurrence of more extensive and physically different migration in the high humidity versus moderate humidity case. Both SE and DVT were stable between six and 18 days postlabeling, the period encompassing the time of maximum exudate formation through the beginning of tissue senescence. Our results suggest that even under conditions that avoid mechanical disturbance of tissue, SE and DVT are chemically stable, at least until senescence, and appear to migrate from the gland region to the epidermal surface, apparently according to their relative polarity. PMID- 24242719 TI - Presence of a hydroxamic acid glucoside in wheat phloem sap, and its consequences for performance ofRhopalosiphum padi (L.) (Homoptera: Aphididae). AB - Phloem sap of wheat seedlings differing in whole leaf hydroxamic acid (Hx) concentrations was collected by cutting stylets of feeding aphids. DIMBOA glucoside was the only Hx-related product found. Concentration of DIMBOA glucoside in phloem sap showed a tendency to be negatively correlated with aphid performance. PMID- 24242720 TI - Molecular basis ofMorinda citrifolia (L.): Toxicity on drosophila. AB - The ripe fruit ofMorinda citrifolia, host plant forDrosophila sechellia is highly toxic for three closely related species (D. melanogaster, D. simulans, andD. mauritiana). Green and rotten fruits are not toxic for all species tested. Short fatty acids were found to be present in large quantities in the extract of the ripe fruit. The most abundant (octanoic acid) was tested pure for its toxicity in a dose-dependent manner;D. sechellia is five to six times more resistant thanD. melanogaster to octanoic acid. Octanoic acid alone seems to be sufficient to explain the toxic effect of the pulp. It is less abundant in the rotten fruit and absent in the green fruit. PMID- 24242721 TI - Biologically active secondary metabolites of barley. IV. Hordenine production by different barley lines. AB - Forty-three lines of barley, including ancestral (wild), landraces, Middle Eastern lines, and modern cultivars, were grown under two different sets of environmental conditions. Hordenine production in barley roots was determined at the one-leaf stage by HPLC analysis and, in two lines only, over a period of 35 days. Forty-two of the 43 lines produced significant amounts of hordenine, although there was no variation among groups. Middle Eastern lines had the highest production with 327 ug/g on a dry weight basis. Production was, however, determined more by environmental conditions during growth than by genetic factors. Hordenine production was up to seven times higher in plants grown under lower light intensities. PMID- 24242722 TI - Plant-natural enemy association in tritrophic system,Cotesia rubecula-Pieris rapae-brassicaceae (Cruciferae). III: Collection and identification of plant and frass volatiles. AB - To elucidate the identity of the volatile compounds that could be involved in the searching behavior of the parasitoidCotesia rubecula Marshall (Hymenoptera: Braconidae), the volatiles released by cabbage and frass of Lepidoptera feeding on cabbage were collected and analyzed using a gas chromatograph-mass spectrometer. The volatiles emitted by intact cabbage were alpha-pinene, beta pinene, myrcene, 1,8-cineole,n-hexyl acetate,cis-3-hexen-1-yl acetate, and dimethyl trisulfide. Mechanical damage on an intact plant induced the release of two more compounds,trans-2-hexenal and 1-methoxy-3-methylene-2-pentanone. Current feeding by larvae ofPieris rapae L. (Pieridae) induced the plant to release all the compounds released after mechanical damage and additionally 4-methyl-3 pentenal and allyl isothiocyanate. Current feeding by larvae ofPlutella xylostella L. (Plutellidae) induced the plant to release all the compounds present after mechanical damage and additionally allyl isothiocyanate. The volatiles emitted after feeding by the lepidopterans had ceased were the same as those emitted by cabbage damaged by mechanical means. The blend of volatiles emitted by frass was comprised of plant chemicals, mainly sulfur compounds. Frass ofP. rapae emitted allyl isothiocyanate, methyl isothiocyanate, methyl propyl sulfide, dimethyl trisulfide,S-methyl methane thiosulfinate, 4-methyl-3 pentenal,trans-2-hexenal, and 2,3-dihydro-4-methyl furan. Frass ofP. xylostella emitted only dimethyl trisulfide andS-methyl methane thiosulfinate. The blend of volatiles emitted by frass is herbivore-species specific. PMID- 24242723 TI - Additional male mediterranean fruitfly (Ceratitis capitata wied.) Attractants from Angelica seed oil (Angelica archangelica L.). AB - Two sesquiterpene hydrocarbons, beta-copaene and beta-ylangene, were isolated from bioactive fractions of angelica seed oil and were shown by field bioassays to be attractive to the male Mediterranean fruit fly. Their relative attractiveness, compared with the(+)-and (-)-alpha-copaene enantiomers, are: (+) alpha-copaene>angelica beta-copaene>angelica beta-ylangene>(-)-alpha-copaene. The enantiomer ratios for the two compounds are: beta-copaene, 61.4% (+), 38.6% (-); beta-ylangene, 91.9% (+), 8.1% (-).trans-alpha-Bergamotene was also isolated from the same fractions, but in sufficient quantity for bioassay [enantiomer ratio: 95.7% (+), 4.3% (-)]. PMID- 24242724 TI - Tannin sensitivity in larvae ofMalacosoma disstria (Lepidoptera): Roles of the peritrophic envelope and midgut oxidation. AB - Final-instarMalacosoma disstria fed artificial diets containing tannic acid develop lethal pupal deformities. We examined some of the factors potentially underlying tannin sensitivity in this species, including the permeability of the peritrophic envelope to tannic acid and the chemical fate of tannic acid in the gut. Tannic acid does not penetrate the peritrophic envelope ofM. disstria, demonstrating that the containment of tannic acid within the endoperitrophic space is not sufficient to protect an insect herbivore from the adverse effects of ingested tannins. Ingested tannic acid undergoes extensive chemical modification in the midgut. Only 19-21 % of the high molecular weight components of the tannic acid ingested was recovered in the frass. Of two possible chemical fates of ingested tannic acid, oxidation is the predominant chemical transformation, whereas little hydrolysis occurs. Measurements of gut redox parameters showed that conditions in the midgut favor the oxidation of phenols. However, similar conditions occur in the midguts ofOrgyia leucostigma, in which no oxidation occurs. Therefore, oxidizing gut redox conditions do not necessarily lead to polyphenol oxidation in lepidopteran larvae. We conclude that the sensitivity ofM. disstria to ingested tannins is a consequence of their oxidation in the midgut. PMID- 24242725 TI - Cellulose digestion in primitive hexapods: Effect of ingested antibiotics on gut microbial populations and gut cellulase levels in the firebrat,Thermobia domestica (Zygentoma, Lepismatidae). AB - Antibiotic feeding studies were conducted on the firebrat,Thermobia domestica (Zygentoma, Lepismatidae) to determine if the insect's gut cellulases were of insect or microbial origin. Firebrats were fed diets containing either nystatin, metronidazole, streptomycin, tetracycline, or an antibiotic cocktail consisting of all four antibiotics, and then their gut microbial populations and gut cellulase levels were monitored and compared with the gut microbial populations and gut cellulase levels in firebrats feeding on antibiotic-free diets. Each antibiotic significantly reduced the firebrat's gut micro-flora. Nystatin reduced the firebrat's viable gut fungi by 89%. Tetracycline and the antibiotic cocktail reduced the firebrat's viable gut bacteria by 81% and 67%, respectively, and metronidazole, streptomycin, tetracycline, and the antibiotic cocktail reduced the firebrat's total gut flora by 35%, 32%, 55%, and 64%, respectively. Although antibiotics significantly reduced the firebrat's viable and total gut flora, gut cellulase levels in firebrats fed antibiotics were not significantly different from those in firebrats on an antibiotic-free diet. Furthermore, microbial populations in the firebrat's gut decreased significantly over time, even in firebrats feeding on the antibiotic-free diet, without corresponding decreases in gut cellulase levels. Based on this evidence, we conclude that the gut cellulases of firebrats are of insect origin. This conclusion implies that symbiont independent cellulose digestion is a primitive trait in insects and that symbiont mediated cellulose digestion is a derived condition. PMID- 24242726 TI - Red maple (Acer rubrum) inhibits feeding by beaver (Castor canadensis). AB - At many beaver (Castor canadensis) sites at Allegany State Park in New York State, red maple (Acer rubrum) is the only or one of the few tree species left standing at the ponds' edges. The relative palatability of red maple (RM) was studied in three ways. (1) At seven beaver sites, the available and utilized trees were recorded and an electivity index (E) computed. Of 15 tree species, RM ranked second or fourth lowest. (2) In experiment I, RM, sugar maple (A. saccharum, SM), and quaking aspen (Populus tremuloides) logs were presented cafeteria style at 10 colonies. RM was the least preferred. (3) Bark of RM was extracted with solvents. Aspen logs were painted (experiment II) or soaked (experiment III) with this RM extract and presented to beaver cafeteria-style, along with aspen and RM controls. This treatment rendered aspen logs less palatable, indicating that a chemical factor had been transferred. PMID- 24242727 TI - Analysis, isolation and insecticidal activity of linear furanocoumarins and other coumarin derivatives fromPeucedanum (Apiaceae: Apioideae). AB - Peucedanum arenarium Waldst. & Kit.,P. austriacum (Jacq.) Koch,P. coriaceum Reichenb.,P. longifolium Waldst. & Kit,P. officinale L.,P. oreoselinum (L.) Moench,P. ostruthium L., andP. palustre (L.) Moench accumulate different structural types of coumarins including simple coumarins, linear furanocoumarins, linear dihydropyranocoumarins, angular dihydrofuranocoumarins and angular dihydropyranocoumarins. Linear furanocoumarins, known for various biological activities, include some well-known antifeedants, such as bergapten, isopimpinellin, and xanthotoxin. The aim of this investigation was to screen the diverse coumarins fromPeucedanum for insecticidal activity. LC was used to analyze and isolate coumarins for the bioassays. A growth inhibition bioassay with 17 derivatives, comprising all structural types fromPeucedanum, carried out withSpodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae) as test organism, indicated the majority of the linear furanocoumarins and the angular dihydrofuranocoumarin athamantin as active compounds. Oxygenation of the prenyl residue of linear furanocoumarins decreased activity. Further formation of an ester with angelic acid even resulted in complete inactivity. Five active linear furanocoumarins, bergapten, isopimpinellin, xanthotoxin, isoimperatorin, and imperatorin, and two linear furanocoumarins with a substituted furan ring, peucedanin and 8-methoxypeucedanin, were compared in a dietary utilization bioassay. Relative growth rate (RGR) and relative consumption rate (RCR) divided the tested coumarins in three groups of similar activity. Isopimpinellin and peucedanin slightly decreased RGR and RCR of the treated larvae, and xanthotoxin, isoimperatorin, and 8-methoxypeucedanin heavily decreased RGR and RCR. Bergapten and imperatorin differed by the lowest RGR values and rather high RCR values. The effects caused by these two coumarins indicate specific postingestive toxicity. The results obtained in this study add to the reputation of coumarins to be an effective chemical defense, postulating that chemical diversity is a necessary trait for well-defended plants. PMID- 24242728 TI - Seasonal variation in volatile secondary compounds ofChrysothamnus nauseosus (Pallas) britt.; asteraceae ssp.hololeucus (Gray) hall. & clem. Influences herbivory. AB - Chrysothamnus nauseosus (rubber rabbitbrush) is used by browsing animals, especially mule deer (Odocoileus hemionus), as a forage in the winter months. It is used only slightly, if at all in the summer. This dietary difference may result from changes in the secondary chemical composition of the leaves. Solvent extracts from summer and winter rabbitbrush leaves were analyzed by gas chromatography and mass spectrometry, and the volatile compounds were quantified and identified. Hexane and chloroform extracts from winter leaves exhibit a marked concentration decrease in most chemicals when compared to summer extracts. The methanol extracts revealed the presence of several chemicals in the summer leaves that were absent in winter leaves. Rubber rabbitbrush has fewer secondary volatile chemicals in the winter than in the summer. These chemical differences may influence the seasonal dietary difference observed in mule deer and other browsing animals. PMID- 24242729 TI - Proximity of release points of pheromone components as a factor confusing males of the spotted stem borer,Chilo partellus, approaching the trap. AB - The effect of proximity of the release points of the two pheromone components (Z) 11-hexadecenal and (Z)-11-hexadecen-1-ol of the spotted stem borer,Chilo partellus (Lepidoptera: Pyralidae) on behavior of the males and on trapping efficiency was investigated. Separating the dispensers of the two components in the trap by a mere 3 cm resulted in a threefold decrease in trap performance, compared to very close release of the components. The result is attributed to possible distortion of the pheromone signal, resulting in confused behavior ofC. partellus males in the vicinity of the trap. The ethological and practical implications of the phenomenon are discussed. PMID- 24242730 TI - Fecal volatiles as part of the aggregation pheromone complex of the desert locust,Schistocerca gregaria (Forskal) (Orthoptera: Acrididae). AB - Olfactometric bioassays showed that nymphs of crowded desert locusts,Schistocerca gregaria, aggregated in response to volatiles derived from their feces and to volatiles emitted from the feces of young adults, but were indifferent to volatiles emitted by older adult feces. On the other hand, young and older adults were not only responsive to their own fecal volatiles but also cross-responsive to each other's and that of the nymphs. Charcoal-trapped volatiles from the feces and synthetic blends of the fecal volatiles also elicited similar responses. Young adults responded moderately to a blend of nymphal volatiles and those derived from nymphal feces. GC-EAD and GC-MS analysis of the trapped volatiles revealed the presence of guaiacol and phenol as predominant electrophysiologically active components of nymphal and young adult feces. Fecal volatiles of older adult contained phenylacetonitrile in addition to guaiacol and phenol, which were present in relatively lower proportion. These results suggest that fecal volatiles are part of the aggregation pheromone complex of the desert locust, which includes the pheromone blends produced by nymphs and older adults, respectively. PMID- 24242731 TI - Isolation of 8-hydroxygeraniol-8-O-beta-D-glucoside, a probable intermediate in biosynthesis of iridoid monoterpenes, from defensive secretions ofPlagiodera versicolora andGastrophysa viridula (Coleoptera: Chrysomelidae). AB - 8-Hydroxygeraniol and its 8-O-beta-D-glucoside have been found as trace components in the defensive secretions ofPlagiodera versicolora andGastrophysa viridula larvae. This discovery supports the hypothesis that the evolution of the utilization of plant precursors by some chrysomelid species was favored by the plesiomorphic occurrence of abeta-glucosidase and an oxidase in the defensive secretion of iridoid-producing species. PMID- 24242732 TI - Squash leaf glandular trichome volatiles: Identification and influence on behavior of female pickleworm moth [Diaphania nitidalis (Stoll.)] (Lepidoptera: Pyralidae). AB - Fourteen volatile compounds occurring in leaf trichomes of yellow squash (Cucurbita pepo L. cv. Early Prolific Straightneck) were identified. These compounds accounted for 83.5% of the volatile matrix. Ubiquitous constituents of the epidermis (myristic, palmitic, and stearic acids,n-tricosane, andn pentacosane) accounted for 73.7%; these compounds were not bioassayed. The volatileso-,m-, andp-xylene, toluene, 2-heptanone, (R)-(+)- and (S)-(-)-limonene, and germacrene D were tested for their influence on attraction and oviposition by the pickleworm moth (Diaphania nitidalis Stoll.). No single compound, except germacrene D, was attractive. (R)-(+)-Limonene and 2-heptanone were weakly repellent. Mixtures of the highly volatile fractions were as attractive as volatiles emanating from whole, intact leaves. Oviposition levels on treated artificial sites corresponded with levels of visitation. Oviposition was significantly stimulated by "whole-leaf" volatiles, and (S)-(-)-limonene caused a slight but significant reduction. PMID- 24242733 TI - Population and sex differences in antipredator responses of breeding fathead minnows (Pimephales promelas) to chemical stimuli from garter snakes (Thamnophis radix andT. sirtalis). AB - We conducted a predator bite survey on a population of fathead minnows (Pimephales promelas) considered to be under substantial predation pressure by western plains garter snakes (Thamnophis radix). Scarring, due to failed predation attempts by garter snakes and crayfish (Orconectes virilis), was observed significantly more often in breeding males than in breeding females and nonbreeding minnows. Likely, territorial nest defense under the edges of rocks along the water's edge, a habitat occupied by crayfish and frequented by snakes, caused the breeding males to be differentially vulnerable to predation. Under controlled laboratory conditions, breeding males from this population exhibited an antipredator response to chemical stimuli from live snakes (T. sirtalis andT. radix) significantly more often than breeding female minnows from the same population and breeding minnows of both sexes from a population that was presumed to be under lower predation pressure from snakes. PMID- 24242734 TI - Isolation of apigeninidin from leaf sheaths ofSorghum caudatum. AB - A stable 3-deoxyanthocyanidin, apigeninidin chloride, a potential fungal growth inhibitor and a useful dye, has been isolated with a high yield (10% in dried material) as the major pigment in the sheaths ofSorghum caudatum. PMID- 24242735 TI - Attacus atlas caterpillars (Lep., Saturniidae) spray an irritant secretion from defensive glands. AB - The ability ofAttacus atlas caterpillars to spray a defensive secretion seems to be due to the fine structure of the integumental glands that produce it. The giant gland cells are fixed to stable cuticular rings surrounding the gland openings and tightly closed by cuticular lids. Probably by increasing hemolymph pressure, the lids are blasted off and the secretion spouts out. The fluid contains several aromatics, biogenic amines (e.g., acetylcholine, histamine), glycerol, and trehalose and exhibits tyrosinase activity. Deterrent effects of caterpillar secretion and hemolymph on predatory ants could be shown. Presumably the spraying process serves to apply the secretion to sensitive sites of vertebrate target organisms. PMID- 24242736 TI - Wound-induced changes in root and shoot jasmonic acid pools correlate with induced nicotine synthesis inNicotiana sylvestris spegazzini and comes. AB - Leaf damage by herbivores inNicotiana sylvestris Spegazzini and Comes (Solanaceae) produces a damage signal that dramatically increasesde novo nicotine synthesis in the roots. The increased synthesis leads to increases in whole-plant nicotine pools, which in turn make plants more resistant to further herbivore attack. Because signal production and the response to the signal occur in widely separated tissues, the speed with which different damage signals exit a damaged leaf can be studied. We propose that electrical damage signals should exit a leaf faster (less than 60 min) than chemical damage signals. Excision of a leaf induces a smaller increase in nicotine production than does puncture damage, so we examined our proposition by excising previously punctured leaves at 1, 60, and 960 min after leaf puncture and quantifying the induced whole-plant nicotine pools six days later when the induced nicotine production had reached a maximum. Significant induced nicotine production occurred only if punctured leaves were excised more than 1 hr after puncture, which is consistent with the characteristics of a slow-moving chemical signal rather than a fast-moving electrical signal. We explore the nature of the chemical signal and demonstrate that additions of 90ug or more of methyl jasmonate (MJ) in an aqueous solution to the roots of hydroponically grown plants inducede novo nicotine synthesis from(15)NO3 in a manner similar to that induced by leaf damage. We examine the hypothesis that jasmonic acid (JA) functions in the transfer of the damage signal from shoot to root. Using GC-MS techniques to quantify whole-plant JA pools, we demonstrate that leaf damage rapidly (<0.5 hr) increases shoot JA pools and, more slowly (<2 hr), root JA pools. JA levels subsequently decay to levels found in undamaged plants within 24 hr and 10 hr for shoots and roots, respectively. The addition of sufficient quantities (186ug) of MJ in a lanolin paste to leaves from hydroponically grown plants significantly increased endogenous root JA pools and increasedde novo nicotine synthesis in these plants. However, the addition of 93ug or less of MJ did not significantly increase endogenous root JA pools and did not significantly affectde novo nicotine synthesis. We propose that wounding increases shoot JA pools, which either directly through transport or indirectly through a systemin-like signal increase root JA pools, which, in turn, stimulate root nicotine synthesis and increase whole-plant nicotine pools. PMID- 24242737 TI - Advanced glycation end products, aortic stiffness, and wave reflection in peritoneal dialysis as compared to hemodialysis. AB - BACKGROUND: Modification of vascular extracellular matrix by advanced glycation end products (AGEs) may result in vascular stiffness. Because of higher exposure to glucose, we hypothesized that patients on peritoneal dialysis (PD) may have higher tissue levels of AGEs, increased vascular stiffness, and enhanced central augmentation pressure as compared to hemodialysis patients (HD). METHODS: In a cross-sectional study, 43 PD were matched to 43 HD based on age, gender, diabetes, and dialysis vintage. Tissue levels of AGEs were assessed by skin autofluorescence (skin AF). Aortic stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV), and heart rate-adjusted augmentation pressure (AP@75) was performed by arterial tonometry. RESULTS: Baseline characteristics were similar in both groups except for lower prevalence of cardiovascular disease (CVD) and higher exposure to smoking in PD. Skin AF and cf-PWV were not statistically different, but PD patients had a lower AP@75 (P = 0.023). However, after adjustments for prevalence of CVD and smoking status, skin AF was higher in PD by 0.587 AU (95 % CI 0.091-1.215, P = 0.020), and cf-PWV was higher in PD by 2.20 m/s (95 % CI 0.56-3.84, P = 0.009), while AP@75 was not different. Overall, there was a significant association between skin AF and cf-PWV and AP@75. CONCLUSION: Skin AF and aortic stiffness were higher in PD after adjustments for imbalances in baseline characteristics. Independent of dialysis modality, there was a positive association between skin AF, aortic stiffness, and enhanced wave reflection. PMID- 24242738 TI - Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis. AB - OBJECTIVES: This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation. METHODS: PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model. RESULTS: Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups. CONCLUSIONS: We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab's role in kidney transplantation. PMID- 24242740 TI - Perceptions of disability and occupational stress as discriminators of work disability in patients with chronic pain. AB - Pain-related work disability can be influenced by a number of medical, physical, and psychosocial factors. The present study investigated the role of perceived disability, occupational stress, pain, and distress in patients with chronic pain disorders who work despite pain and patients who are work disabled. A total of 165 patients referred to a multidisciplinary pain treatment center for chronic pain (> 6 months) were studied. The two groups were compared on age, gender, education, marital status, duration of pain problem, pain severity, psychological distress, perceived disability, and perception of the work environment. A discriminant function analysis was computed entering pain severity, distress, perceived disability (physical and psychosocial) and work environment variables. The two groups were equivalent on age, gender, education, marital status, and duration of pain problem. The groups differed on diagnosis and insurance coverage with the work-disabled group diagnosed with low back pain and receiving Workers Compensation coverage more frequently than working controls. Univariate analyses indicated that the work-disabled group reported higher pain severity, perceived physical and psychosocial disability, and job stress than their working cohorts. The discriminant function analysis indicated that the perception of physical disability, supervisor support, distress, and work pressure were capable of correctly classifying patients with chronic pain who continued to work from those who were work disabled. These findings indicate the importance of evaluating perceived disability and job stress, and if present, directing intervention effort at these factors in order to facilitate work re-entry. PMID- 24242739 TI - The prognostic value of cyclin D1 in renal cell carcinoma. AB - INTRODUCTION: Renal cell carcinoma (RCC) is a family of distinct tumors, and a variety of molecules have been evaluated as prognostic markers for RCC. Cyclin D1, a cell cycle regulator, is overexpressed in several primary tumors. OBJECTIVE: To evaluate cyclin D1 expression as a prognostic marker in RCC. METHOD: In total, 109 tumor specimens from patients with RCC were obtained from 2005 to 2010 at Hospital das Clinicas--Ribeirao Preto School of Medicine--USP, Brazil, and submitted to immunohistochemical analysis along with seven normal kidney tissue samples. RESULTS: All of the normal kidney samples lacked cyclin D1 immunohistochemical staining. In addition, there was lower protein expression in the papillary and chromophobe RCC samples. Patients with cyclin D1(low) tumors (<= 30 % positive cells) showed worse clinical outcome (p = 0.03), lower survival without metastasis and/or death by RCC (p = 0.03), high nuclear grade (p = 0.001), larger tumor size (p = 0.01), presence of symptoms at diagnosis (p = 0.04), necrosis (p = 0.004) and sarcomatoid morphology (p = 0.04). After multivariate analysis, cyclin D1 was not an independent significant factor for worse outcome; however, it improved the accuracy of the adopted prognostic system. The analysis performed for clear cell RCC alone showed similar statistical significance to that of the total cases. CONCLUSIONS: Cyclin D1 protein was overexpressed in RCC. The types of RCC appear to exhibit different immunohistochemical staining patterns for cyclin D1; high protein expression was related to good clinical outcome and to most known favorable prognostic factors. Further investigations are necessary to reveal which mechanisms lead to cyclin D1 accumulation in neoplastic cells. PMID- 24242741 TI - A comparison of isometric strength and dynamic lifting capacity in men with work related low back injuries. AB - Job classification, return to work status, and job placement are determined by the results of lifting capacity tests. Lifting capacity is often assessed by maximum static or dynamic physical exertions. The purpose of this study was to compare maximum isometric lifting strength with maximum dynamic lifting capacity in subjects with work-related low back injury. Twenty-seven men performed five dynamic lifting tasks and two isometric strength tests. The mean Pearson product moment correlation between maximum isometric lifting strength measurements and maximum dynamic lifting capacity measurements was .51 with a range of .30-.73. The results indicate low to moderate associations between isometric strength measurements and lifting capacity suggesting that estimates of functional lifting capacity should not be based on static measurements alone. Dynamic lift tests are often a better simulation of the task being assessed and may be more appropriate for a back-injured population. PMID- 24242742 TI - Functional restoration for chronic low back pain: Changes in depression, cognitive distortion, and disability. AB - In the present study, 107 patients (72 males and 35 females) completed self report measures of depression, distortion, disability, and pain intensity at three points during their rehabilitation: (1) admission to a 3-week comprehensive functional restoration program, (2) discharge from the comprehensive phase, and (3) 4-6 weeks later at their first post-program evaluation. Various range-of motion measures were also collected at these same times using inclinometry. Results demonstrated significant improvements on all measures which were maintained into follow-up. Patients were also subsequently grouped into depressed and non-depressed at admission, and both groups demonstrated significant improvement across time. Additionally, patients were divided into high and low distortion groups. High general cognitive distortion patients did not show improvement on 3 of the 5 range of motion, or pain intensity scores, although they did improve on their depression, distortion, and disability scores. Findings also suggested thatlow back pain-related cognitive distortion may be considered a state or situational factor, whereasgeneral cognitive distortion appears to be more of a trait characteristic. PMID- 24242743 TI - Biomechanical analysis of upper extremity risk in Sign Langauge Interpreting. AB - Upper extremity cumulative trauma distorders (UECTD) have been identified as an occupational health problem in professional Sign Language Interpreters (SLI). A previous study of UECTD in SLI has indicated significant differences between interpreters working with pain and those working without pain. This earlier research focused on gross measures of hand/wrist movement, work/rest cycles, and deviations from an optimal work envelope. The present paper describes a detailed biomechanical analysis of wrist and forearm activity associated with SLI. This assessment included forearm (flexion and extension) and wrist (flexion/extension and radial/ulnar deviation) measures of movement frequency, counts of individual motion, joint movement velocities and accelerations as well as range of motion. The analyses revealed that the postures required for interpreting result in the signing hand frequently held in a fully pronated position, with the palm facing out. The wrist was most frequently in an ulnar deviation and/or extension while the elbow was flexed more than 90 degrees and held in close to the body with the fingers pointing up. The frequency of motions for the forearm and wrist were observed to be 270 per minute (4.5 Hz), which is equivalent to 13,600 per 50 minute lecture hour. The mean absolute joint movement velocity and acceleration values were relatively high in contrast to industrial jobs with wrist and forearm accelerations between 34,754 degreees/sec(2) and 36,046 degrees/sec(2), respectively. The findings from this biomechanical analysis indicates that SLI can involve highly repetitive, awkward movements with significant accelerations of the hand and wrist. Such job characteristics may predispose interpreters to upper extremity CTD-related disorders. PMID- 24242744 TI - Prior psychiatric problems in rehabilitation clients with work-related injuries. AB - Psychiatric histories were obtained in 56 patients beginning rehabilitation following a work-related injury in order to establish the temporal relationship between the onset of psychiatric problems and the date of the work injury. The presence of major depression and alcohol abuse was determined using structured, directed interviews and the criteria set forth in the Diagnostic and Statistical Manual of Mental Disorders. A history of either alcohol abuse or depression was found in 36 (64.3%) of the 56 subjects. Of these 36 subjects, 32 (88.9%) reported a history of psychiatric problems that antedated the work injury. These data suggest that, in injured workers, the conceptualization of psychiatric problems solely as reactive illnesses in otherwise psychiatrically healthy persons is often inaccurate. Furthermore, these data suggest the hypothesis that the presence of clinical depression or alcohol abuse may increase the risks of a work related injury. PMID- 24242745 TI - The functional restoration approach for chronic spinal disability. AB - The functional restoration approach to treating chronic spinal disability consists of a medically directed, interdisciplinary team approach to physical reconditioning and a cognitive-behavioral "crisis intervention" procedure for dealing with related psychosocial problems. One- and two-year follow-up studies have demonstrated the clinical efficacy of this approach. The present article describes this approach and summarizes the research documenting its success in treating patients with chronic spinal disability. This article also highlights the pitfalls in misunderstanding and misrepresenting the components of the functional restoration approach when evaluating treatment efficacy. PMID- 24242747 TI - The crane's foot: The rise of the pedigree in human genetics. AB - The standard pedigree used by geneticists is intimately connected to the history of genetics. Pedigrees drawn today are based on standards established in the early decades of the twentieth century. Those standards were established by geneticists who pursued an active interest in eugenics. The slightly different standards followed in America vs. England to some extent followed the stronger support of Mendelism by the Americans, as well as the individual preferences of the leading human geneticists in those countries. PMID- 24242746 TI - Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. AB - OBJECTIVE: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. METHODS: CSF NfL, amyloid-beta1-42 (Abeta42), tau, and phosphorylated tau concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, and 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer disease, 6 Parkinson disease, and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural magnetic resonance images determined the relationship between brain volume and CSF NfL. RESULTS: Mean CSF NfL concentrations were higher in bvFTD, SD, and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, but not in other diagnostic groups. Analyses in 2 independent FTD cohorts and a group of autopsy-verified or biomarker-enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with the highest NfL levels exhibited the most atrophy. INTERPRETATION: CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. PMID- 24242748 TI - The need for developing standardized family pedigree nomenclature. AB - To assess the variation in usage of symbols used in recording a genetic family history, full members of the National Society of Genetic Counselors were surveyed by questionnaire. The questionnaire return rate was 55.3% and genetic counselors from a broad range of clinical experience, genetic counseling training programs and geographic regions responded. There was striking variation in symbols used for recording routine medical information in a genetic family history (i.e., pregnancy, spontaneous abortion, termination of pregnancy). There was even less consensus in recording situations representing new reproductive technologies (i.e., artificial insemination by donor semen, donor ovum, surrogate motherhood). The results of this survey document the need for developing standardized nomenclature in recording genetic family histories as a quality assurance measure in the delivery of genetic services. Such standardization will reduce the chance of incorrect interpretation of patient and family medical and genetic information. PMID- 24242749 TI - Toward a new conceptualization and operationalization of risk perception within the genetic counseling domain. AB - The purpose of this paper is twofold. First, it provides an historical overview of studies of risk, risk perception, and decision making under risk within the genetic counseling domain. Second, it proposes an alternative conceptualization and operationalization for the study of risk perception. The conceptualization involves probability, adversity, incompleteness, and ambiguity. Prior studies of risk perception focus on the recurrence risk and operationalize risk perception by asking for interpretations of the magnitude of the probability of the outcome. Their focus is on the probability of a particular outcome. We formulate the problem in terms of a gamble and suggest that risk perception be operationalized in terms of the riskiness of the gamble. Our focus is on the riskiness of a decision option which entails two or more outcomes. PMID- 24242750 TI - Genetic library. PMID- 24242751 TI - Abstracts of papers at the twelfth annual education conference. PMID- 24242752 TI - Editor's note. PMID- 24242753 TI - CF Reinbursement questioned. PMID- 24242754 TI - Prevalence of HIV infection and risk behaviors among younger and older injecting drug users in the United States, 2009. AB - This study compared HIV sero-prevalence and risk behaviors between younger and older injecting drug users (IDUs). IDUs aged >=18 years were interviewed for the 2009 National HIV Behavioral Surveillance System. Using GEE regression, we assessed characteristics of younger (18-29 years) and older (>=30 years) IDUs, and factors associated with past 12-month receptive syringe sharing and unprotected sex (vaginal/anal). Of 10,090 participants, 10 % were younger. HIV sero-prevalence was lower among younger than older IDUs (4 vs. 10 %, p = 0.001). Younger IDUs were more likely (p <= 0.002) to be non-black race/ethnicity, report higher household income, homelessness, being arrested and to engage in receptive syringe sharing and unprotected sex. In multivariable models, age remained associated (p < 0.001) with receptive syringe sharing (aPR = 1.14, 95 % CI1.07 1.22) and unprotected sex (aPR = 1.10, 95 % CI1.06-1.14). Although younger IDUs had lower HIV prevalence, their behaviors place them at increased risk of HIV infection and could lead to a rapid spread in this susceptible population. PMID- 24242755 TI - Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study. AB - Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer. PMID- 24242756 TI - Glioblastoma treatment using perphenazine to block the subventricular zone's tumor trophic functions. AB - We present here a potential new treatment adjunct for glioblastoma. Building on murine studies, a series of papers appeared recently showing that therapeutic irradiation of the ipsilateral subventricular zone (SVZ) retards growth of more peripherally growing cortical glioblastomas in humans, suggesting a tumor trophic function for the SVZ. Further studies showed that SVZ cells migrate out towards a peripheral glioblastoma. Dopamine signaling through D3 subtype receptor indirectly drives this centrifugal migration in humans. Since psychiatry has several drugs with good D3 blocking attributes, such as fluphenazine, or perphenazine, we suggest that adding one of these D3 blocking drugs to current standard treatment of resection followed by temozolomide and irradiation might prolong survival by depriving glioblastoma of the trophic functions previously subserved by dopaminergic signaling on SVZ cells. PMID- 24242757 TI - Molecular analysis of diffuse intrinsic brainstem gliomas in adults. AB - Diffuse intrinsic brainstem gliomas (DIBG) account for 1-2 % of adult gliomas. Their biological characteristics are scarcely understood and whether DIBG are biologically different from supratentorial gliomas remains to be established. We analyzed 17 DIBG samples for IDH1 R132H, alpha internexin, p53, and Ki67 expression, and, in a subset with sufficient DNA amount, for IDH1 and histone H3 mutational status, genomic profiling and MGMT promoter methylation status. A series of 738 adult supratentorial gliomas was used for comparison. Median age at diagnosis was 41 years (range 18.9-65.3 years). Median overall survival was 48.7 months (57 months for low-grade vs. 16 months for high-grade gliomas, p < 0.01). IDH1 sequencing revealed two mutations (IDH1 (R132G) , IDH1 (R132C) ) out of 7 DIBG whereas the R132H IDH1 enzyme was detected in 1/17 DIBG, suggesting that IDH1 mutations are mostly non R132H in DIBG (2/2), in contrast to supratentorial gliomas (31/313; p = 0.01). Mutations in histone genes H3F3A (encoding H3.3) and HIST1H3B (encoding H3.1) were found in 3/8 (37.5 %) of the DIBG (two H3F3A (K27M) and one HIST1H3B (K27M) ) versus 6/205 (2.9 %) of the supratentorial high-grade gliomas (four H3F3A (G34R) and two H3F3A (K27M) ) (p = 0.002). The CGH array showed a higher frequency of chromosome arm 1q gain, 9q gain and 11q loss in DIBG compared to the supratentorial high-grade gliomas, which had a less frequent chromosome 7 gain, and a less frequent chromosome 10 loss. No EGFR amplification was found. These data suggest that adult DIBG differ from adult supratentorial gliomas. In particular, histone genes (H3F3A (K27M) , HIST1H3B (K27M) ) mutations are frequent in adult DIBG whereas IDH1 (R132H) mutations are rare. PMID- 24242758 TI - STAT4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis. AB - We and others have previously shown that IL-12 is indispensable for immunity and is required for the optimal antiparasitic activity of antimonials in experimental visceral leishmaniasis caused by Leishmania donovani. Here we investigated the role of STAT4 in immunity against L. donovani using STAT4 knockout mice and also determined the effect of STAT4 deficiency in response to antimonial therapy. Upon infection with L. donovani, stat4-/- BALB/c and C57BL/6 mice showed enhanced susceptibility to Leishmania during late time points of infection which was associated with a marked reduction in Th1 responses and hepatic immunopathology. Interestingly, these defects in Th1 responses in stat4-/- did not impair the antimonial chemotherapy as both stat4-/- and WT mice showed comparable levels of parasite clearance from the liver and spleen. These findings highlight the role of STAT4 in immunity to L. donovani infection and also provide evidence that STAT4 is dispensable for antimonial-based chemotherapy. PMID- 24242759 TI - MicroRNAs in islet immunobiology and transplantation. AB - The ultimate goal of diabetes therapy is the restoration of physiologic metabolic control. For type 1 diabetes, research efforts are focused on the prevention or early intervention to halt the autoimmune process and preserve beta cell function. Replacement of pancreatic beta cells via islet transplantation reestablishes physiologic beta cell function in patients with diabetes. Emerging research shows that microRNAs (miRNAs), noncoding small RNA molecules produced by a newly discovered class of genes, negatively regulate gene expression. MiRNAs recognize and bind to partially complementary sequences of target messenger RNA (mRNA), regulating mRNA translation and affecting gene expression. Correlation between miRNA signatures and genome-wide RNA expression allows identification of multiple miRNA-mRNA pairs in biological processes. Because miRNAs target functionally related genes, they represent an exciting and indispensable approach for biomarkers and drug discovery. We are studying the role of miRNA in the context of islet immunobiology. Our research aims at understanding the mechanisms underlying pancreatic beta cell loss and developing clinically relevant approaches for preservation and restoration of beta cell function to treat insulin-dependent diabetes. Herein, we discuss some of our recent efforts related to the study of miRNA in islet inflammation and islet engraftment. Our working hypothesis is that modulation of the expression of specific microRNAs in the transplant microenvironment will be of assistance in enhancing islet engraftment and promoting long-term function. PMID- 24242762 TI - Immunology and microbiology in Miami. PMID- 24242761 TI - A20-mediated negative regulation of canonical NF-kappaB signaling pathway. AB - The nuclear factor kappa B (NF-kappaB) plays vital role in the immune system by regulating innate and adaptive immunity, development and survival of lymphocytes, and lymphoid organogenesis. All known NF-kappaB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF kappaB pathways. The IKK complex contains two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit NEMO/IKKgamma that regulates the canonical NF kappaB pathway, whereas IKKalpha regulates the non-canonical pathway. The process of IKKalpha activation and its role in the regulation of canonical NF-kappaB activation remain elusive. The canonical pathway is rapidly activated and produces a potent inflammatory response to bacterial and viral infections as well as different types of stress; however, uncontrolled NF-kappaB activation can lead to autoimmune diseases and cancers. Therefore, to keep the inflammatory response in check, elaborate negative regulatory mechanisms operate to terminate NF-kappaB activation at multiple levels by de novo synthesis of NF-kappaB inhibitory proteins, and orchestration of protein ubiquitination and deubiquitination. The NF-kappaB target genes, IkappaBalpha and A20, play critical roles in termination of the active canonical NF-kappaB pathway. In this review, we discuss our recent findings describing a novel function for IKKalpha in nucleating the ubiquitin editing enzyme A20 complex, a major negative regulator of canonical NF-kappaB signaling. Consistently with an inhibitory function of IKKalpha, it is targeted by the human T-cell leukemia virus 1 (HTLV-1) oncoprotein, Tax, to prevent assembly of the A20 complex to maintain persistent NF-kappaB activation that promotes transformation and survival of virus-transformed cells. PMID- 24242763 TI - Mesenchymal stem cells ameliorate cerebellar pathology in a mouse model of spinocerebellar ataxia type 1. AB - Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disorder caused by the expansion of a polyglutamine tract in the ataxin-1 protein. To date, no fundamental treatments for SCA1 have been elucidated. However, some studies have shown that mesenchymal stem cells (MSCs) are partially effective in other genetic mouse models of cerebellar ataxia. In this study, we tested the efficacy of the intrathecal injection of MSCs in the treatment of SCA1 in transgenic (SCA1-Tg) mice. We found that intrathecal injection of only 3 * 10(3) MSCs greatly mitigated the cerebellar neuronal disorganization observed in SCA1 transgenic mice (SCA1-Tg mice). Although the Purkinje cells (PCs) of 24-week-old nontreated SCA1-Tg mice displayed a multilayer arrangement, SCA1-Tg mice at a similar age injected with MSCs displayed monolayer PCs. Furthermore, intrathecal injection of MSCs suppressed the atrophy of PC dendrites in SCA1-Tg mice. Finally, behavioral tests demonstrated that MSCs normalized deficits in motor coordination in SCA1-Tg mice. Future studies should be performed to develop optimal protocols for intrathecal transplantation of MSCs in SCA1 model primates with the aim of developing applications for SCA1 patients. PMID- 24242764 TI - The development of a high resolution mass spectrometer: A reminiscence. AB - This article is a review of the events leading to the development of the double focusing tandem mass spectrometer system, which is sometimes called the Johnson Nier geometry. An essential feature of the geometry is that it eliminates second order angular aberration, enhancing the sensitivity, without a loss in resolution. Flexibility in the choice of ion source and collector designs is assured because both are outside of regions of electric and magnetic fields. The vacuum housing permits high-temperature baking, ensuring ultrahigh vacuum conditions. Although introduced initially for the purpose of determining precise atomic masses, the design has found its greatest application in studies of structure of heavy molecules, making use of the high resolution to identify fragments. In many cases the composition of a molecule, or fragment, can be deduced from its exact mass by utilizing the known atomic masses of likely constituent atoms. PMID- 24242760 TI - Interleukin-21 and T follicular helper cells in HIV infection: research focus and future perspectives. AB - Interleukin (IL)-21 is a member of the gamma chain-receptor cytokine family along with IL-2, IL-4, IL-7, IL-9, and IL-15. The effects of IL-21 are pleiotropic, owing to the broad cellular distribution of the IL-21 receptor. IL-21 is secreted by activated CD4 T cells and natural killer T cells. Within CD4 T cells, its secretion is restricted mainly to T follicular helper (Tfh) cells and Th17 cells to a lesser extent. Our research focus has been on the role of IL-21 and more recently of Tfh in immunopathogenesis of HIV infection. This review focuses on first the influence of IL-21 in regulation of T cell, B cell, and NK cell responses and its immunotherapeutic potential in viral infections and as a vaccine adjuvant. Second, we discuss the pivotal role of Tfh in generation of antibody responses in HIV-infected persons in studies using influenza vaccines as a probe. Lastly, we review data supporting ability of HIV to infect Tfh and the role of these cells as reservoirs for HIV and their contribution to viral persistence. PMID- 24242765 TI - On the structure of protonated methane. AB - Results of a Fourier transform-ion cyclotron resonance study are reported concerning the reactivity of protonated perdeuteromethane and deuteronated methane, generated under varying pressure conditions in an external chemical ionization ion source, toward ammonia. The competition between proton and deuteron transfer from both protonated perdeuteromethane and deuteronated methane to ammonia exhibits chemically distinguishable hydrogens. The chemical behavior of protonated methane appears to be compatible with the theoretically predicted stable structure with Cs symmetry, involving a three-center two-electron bond associating two hydrogens and the carbon atom. Interconversion of this structure due to exchange between one of these hydrogens and one of the three remaining hydrogens appears to be a fast process that is induced by interactions with the chemical ionization gas. PMID- 24242766 TI - Protonated ethanol and its neutral counterparts. AB - Collisionally activated dissociation and neutralization-reionization experiments reveal that protonation of ethanol leads to two distinct isomers, the classical ion CH3CH2OH+2 and the proton-bound complex C2H4... H+... OH2. The neutral counterpart of the latter is unstable, whereas that of the former can be produced in a bound state if the CH3CH2OH+2 precursor ion is formed under low ion source pressure conditions and, thus, with higher internal energies. This suggests that there are substantial differences in the geometries of CH3CH2OH(+) 2 and the hypervalent CH3CH2OH2.. This provides only a partial explanation for unusual isotope effects; C2H5OD2., CH3CD2OD2., and CD3CH2OD2. are substantially more stable than C2D5OD2 . and C2H5OH2.. PMID- 24242767 TI - Dissociation dynamics of phenetole cations by photoelectron photoion coincidence. AB - The dissociation rates of phenetole ions have been measured as a function of the ion internal energy by the method of photoelectron photoion coincidence spectrometry. The loss of ethylene to produce the phenol ion is the only dissociation pathway from its onset at 9.17 eV up to at least 12 eV. An activation energy of 1.64 +/- 0.06 eV with an assumed activation entropy of + 18 +/- 4 cal/mol-K is derived from fitting the statistical theory decay rates to the measured rates. The transition state energy lies ~ 1 eV below the thermochemical dissociation limit to the C2H 5 (+) + C6H5O . products. It is thus unlikely that an ion-radical complex is involved in the production of the phenol ion. PMID- 24242768 TI - Fast atom bombardment tandem mass spectrometry employing ion-molecule reactions for the differentiation of phospholipid classes. AB - Fast atom bombardment tandem mass spectrometry, employing ion-molecule reactions with ethyl vinyl ether in a triple-quadrupole mass spectrometer, is used to differentiate classes of phospholipids. The phospholipids are desorbed and ionized by fast atom bombardment, mass-selected by the first quadrupole, and reacted with ethyl vinyl ether in the second quadrupole; the resulting product ions are analyzed by the third quadrupole. The protonated molecules and reaction product ions observed permit the differentiation of various phospholipid classes. The pattern of addition reaction products formed is shown to depend solely on the functionality of the lipid polar head group and not on the fatty acyl constituents. Neutral gain scans that are specific for each phospholipid class are performed. Ion dissociation products are observed in the same scan as the ion reaction products to provide data on the fatty acyl composition and position on the glycerophosphate COre along with the phospholipid class. Although this method is less sensitive than neutral loss scanning for most phospholipid classes, it can (1) identify phospholipids that do not readily lose their head group as a neutral fragment and (2) detect phospholipids in mixtures containing species that give interfering neutral losses. PMID- 24242769 TI - Novel mass spectral fragmentation of heptafluorobutyryl derivatives of acyl analogues of platelet-activating factor. AB - Direct derivatization of the acyl analogue of platelet-activating factor (acyl.PAF) with heptafluorobutyric anhydride results in replacement of the phosphocholine moiety with a heptafluorobutyryl (HFB) group. Electron capture (EC) mass spectrometric analysis of this compound that makes use of negative ion detection along with subsequent accurate mass measurement and tandem mass spectrometry studies revealed that in addition to expected fragmentation due to losses of elements of HF, ketene, and/or acetic acid, there is a rearrangement reaction between the HFB group and the subsequent on carbon-2 of the glycerol backbone. For 2-acetyl isomers, this fragmentation yields a characteristic ion at m/z 237; for 1-acetyl isomers, the analogous ion is observed at [M-135](-), along with a corresponding carboxylate anion. The use of the HFB derivative is invaluable for analysis of PAF homologues and analogues because it provides detailed structural information in combination with the high sensitivity of a gas chromatography combined with EC-mass spectrometry assay. PMID- 24242770 TI - Linear response theory of ion excitation for Fourier transform mass spectrometry. AB - A linear relation between the voltage density or magnitude spectrum of an excitation waveform and the corresponding ion orbital radius is derived for Fourier transform mass spectrometry (FTMS). This provides a theoretical foundation for the stored waveform inverse Fourier transform excitation method. The result is also useful for the design of optimal excitation signals as well as for the estimation of the kinetic energy of ions after an excitation event in collision-induced dissociation experiments. When the linear relation is applied to two-dimensional FTMS excitation, an analytical expression for ion speed modulation is obtained. PMID- 24242771 TI - Surface-induced dissociation of molecular ions in a quadrupole ion trap mass spectrometer. AB - A method is reported by which surface-induced dissociation is used to activate ions stored in a quadrupole ion trap mass spectrometer. The method employs a short (< 5 /-Is), fast-rising (< 20-ns rise time), high voltage direct current (dc) pulse, which is applied to the endcaps of a standard Paul-type quadrupole ion trap. This is in contrast to the application of an alternating current (ac) signal normally used to resonantly excite and dissociate ions in the trap. The effect of the de pulse is to cause the ions rapidly to become unstable in the radial direction and subsequently to collide with the ring electrode. Sufficient internal energy is acquired in this collision to cause high energy fragmentations of relatively intractable molecular ions such as pyrene and benzene. The dissociations of limonene are used to demonstrate that high energy demand processes increase in relative importance in the dc pulse experiment compared with the usual resonance excitation method used to cause activation. The fragments are scanned out of the ion trap using the conventional mass-selective instability scan mode. Simulations of ion motion in the trap provide evidence that surface collisions occur at kinetic energies in the range of tens to several hundred electronvolts. The experiments also demonstrate that production of fragment ions is sensitive to the phase of the main radiofrequency drive voltage at the point when the dc is initiated. PMID- 24242772 TI - Angle-resolved neutralization-reionization mass spectrometry. AB - Neutralization -reionization mass spectra of 2-propenal, isomeric butenes, and isomeric n-hexenes have been found to depend significantly on the z-axis scattering angle of the neutralization event. As shown by Cooks for ion dissociations, increasing scattering angles generally favor products of higher activation-energy reactions. For isomeric butenes and n-hexenes, these reactions provide more definitive information for isomeric characterization. PMID- 24242773 TI - Electrospray mass spectrometry of methanol and water solutions suppression of electric discharge with SF6 gas. AB - An equation by D. P. H. Smith predicts the capillary voltage required for the onset of electrospray (ES). For different solvents the voltage increases with the square root of the surface tension. Water requires a potential that is 1.8 times higher than that for methanol. This is verified experimentally. The higher potential required for water leads to ES in the presence of corona electric discharge. For low total ES plus corona currents, the electrosprayed analyte ion intensity is not adversely affected by the presence of discharge. At high total currents, there is a large decrease of analyte sensitivity. The sensitivity decrease is probably due to adverse space charge effect at high currents. The discharge can be suppressed by adding sulfur hexafluoride to the ambient gas. Both sensitivity and signal stability are improved. However, the sensitivity still remains lower by a factor of - 4 relative to that observed with methanol. This is attributed to lower efficiency of gas-phase ion formation from charged water, relative to methanol, droplets. PMID- 24242774 TI - A high transmission hemispherical energy analyzer for ion spectrometry. AB - A hemispherical energy analyzer was constructed by using a novel approach to control the fringing electrostatic field. It provides several properties useful in ion spectrometers: namely, rather simple fabrication and compact size, high transmission efficiency at moderate resolution, and the capability to adjust resolution by changing the intersphere potentials. A computer program was developed to evaluate ion trajectories through the hemispherical analyzer. Data obtained from the trajectories were used to predict the characteristics of the analyzer. Experiments performed to determine the kinetic energy dependence of the absolute transmission and the resolution functions are in accord with theoretical calculations. PMID- 24242777 TI - A step forward in laparoscopic hepatectomy: comments on "Expert consensus on laparoscopic hepatectomy (2013 version) by National Hepatic Surgery Group, Society of Surgery, Chinese Medical Association". PMID- 24242776 TI - The role of prophylactic transpapillary pancreatic stenting in distal pancreatectomy: a meta-analysis. AB - Pancreatic fistula (PF) is the most frequent complication after distal pancreatectomy (DP). Prophylactic transpapillary pancreatic stenting (PTPS) has been proposed recently for the prevention of PF after DP. In this meta-analysis, a comprehensive search was performed in the PubMed, Embase, and Cochrane Library databases. Studies analyzing the results of PTPS in DP were considered eligible for this meta-analysis. The analyzed outcome variables included PF rate, postoperative morbidity, non-PF-related complications, mortality, operation duration, and hospital stay. Four studies with 200 patients were included in this review. Only one was a randomized controlled trial (RCT). The results showed that PTPS was associated with less PF formation (odds ratio, 0.45; 95% confidence interval [CI], 0.22-0.94; P = 0.03) and shorter hospital stay (mean difference, - 6.31; 95% CI, - 6.99 to - 5.62; P < 0.00001). There was no significant difference in terms of the other variables. In conclusion, current evidence indicates that PTPS could reduce PF incidence and hospital stay after DP, without increasing other complications or operative time. However, the evidence is not solid, because the single RCT conflicted with the other three retrospective reports. Thus, considering the limitation, more well-designed RCTs on this topic are needed in the future. PMID- 24242778 TI - Subocclusal dental morphology of sahelanthropus tchadensis and the evolution of teeth in hominins. AB - The evolution of the teeth in hominins is characterized by, among other characters, major changes in root morphology. However, little is known of the evolution from a plesiomorphic, ape-like root morphology to the crown hominin morphology. Here we present a study of the root morphology of the Miocene Chadian hominin Sahelanthropus tchadensis and its comparison to other hominins. The morphology of the whole lower dentition (I1 -M3 ) was investigated and described. The comparison with the species Ardipithecus kaddaba and Ardipithecus ramidus indicates a global homogeneity of root morphology in early hominins. This morphology, characterized notably by a reduction of the size and number of the roots of premolars, is a composite between an ape-like morphology and the later hominin morphology. Trends for root evolution in hominins are proposed, including the transition from a basal hominoid to extant Homo sapiens. This study also illustrates the low association between the evolution of tooth root morphology and the evolution of crowns in hominins. PMID- 24242780 TI - Editorial comment. PMID- 24242779 TI - GRP78 expression and regulation in the mouse uterus during embryo implantation. AB - The aim of this study was to investigate the spatiotemporal expression and regulation of GRP78 in the mouse uterus during the peri-implantation period. The GRP78 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy. On day 5 of pregnancy, the GRP78 protein was more highly observed around the implanted embryo at the implantation site. There was no detectable GRP78 protein signal on day 5 of pseudopregnancy. GRP78 mRNA and protein levels gradually increased on days 6-8 of pregnancy, and the expression pattern was also expanded, coinciding with the development of decidua. Similarly, GRP78 expression was also strongly expressed in decidualised cells following artificial decidualisation. Compared with the results obtained with the delayed uterus, a high level of GRP78 expression was detected in the implantation activated uterus. In the uteri of ovariectomised mice, GRP78 expression increased and reached its highest level after injection of oestrogen, and progesterone seemed to have an antagonistic effect on oestrogen up-regulation of GRP78 expression. Our data indicate that GRP78 might play an important role during the process of mouse embryo implantation, and GRP78 expression was mainly regulated by active blastocysts and maternal oestrogen. PMID- 24242781 TI - Social labeling, stereotyping, and observer bias in workers' compensation: The impact of provider-patient interaction on outcome. AB - When injured workers with chronic musculoskeletal disorders are viewed through the narrow lens of the biomedical model, the role of situational factors is not acknowledged, and their illness behaviors and delayed recovery are often attributed to personal weakness or a desire for secondary gain. This leads to a tendency toward blame and the application of stigmatizing social labels. An overt or implied social label that carries a stigma can set into motion therapeutically counterproductive biases in social perception within the provider-patient relationship. One of most powerful of these has been called the self-fulfilling prophecy, in which expectancy-driven behaviors of the clinician, case manager, or insurance representative can subtly direct the patient to behave in a manner consistent with expectations. Justification for an attitudinal shift among providers of workers' compensation services is proposed, along with application of the biopsychosocial framework of health psychology to the problem of delayed recovery in injured workers. PMID- 24242782 TI - Prediction of return to work by rehabilitation professionals. AB - Rehabilitation therapists made predictions of return to work for 57 patients evaluated prior to beginning a work-hardening program. These predictions, along with 14 specific demographic, injury, and physical function measures were entered into a stepwise discriminant analysis to develop a predictive model for return to work. Therapists correctly predicted the eventual return to work for 47 (73.7%) of the 57 subjects. Therapist prediction was the most powerful variable in the model, explaining 29% of the variance (p<=.0001). Only two other variables, self report of pain severity and injury type, contributed significantly to the prediction model, accounting respectively for 12% and 9% of the variance (p's<.05). These data highlight the predictive acuity of rehabilitation therapists and suggest that the process involved in formulating clinical predictions merits further study. The findings also suggest that weighing information such as self-report of pain severity and injury type might further enhance the practitioner's ability to predict return to work. PMID- 24242783 TI - Comprehensive treatment approach for lower back workers' compensation injuries. AB - A clinical outcome follow-up comparison of treatment and non-treatment groups was conducted to investigate the clinical effectiveness of a hospital-based occupational rehabilitation program. Twelve-month follow-up data were collected on 44 patients participating in a comprehensive treatment program and 20 patients referred for treatment but denied participation by their workers' compensation insurance company. Outcome data indicate that the population of workers' compensation low back injured patients who participated in occupational rehabilitation treatment subsequently were more likely to return to employment, consumed fewer analgesics, required fewer hospitalizations for additional diagnostics and/or treatment, and required fewer additional surgeries than a comparison group of patients denied comparable treatment. PMID- 24242784 TI - A critical review of questionnaires for assessing pain-related disability. AB - Standardized questionnaires offer a practical and cost-effective means for measuring moderate disability. Fourteen questionnaires that can be used for assessing pain-related disability are reviewed in this article. Their comparative attributes are summarized. Most of the questionnaires obtain information about specific activities of daily living. They vary in terms of structure, content, and intended applications. Psychometric theory provides the optimal method for evaluating these questionnaires, highlighting the importance of reliability and validity. Being mindful of psychometric qualities will help the evaluator to select an appropriate questionnaire. The present array of existing instruments points toward a need for comparison studies that may eventually result in more uniform methods for evaluating pain-related disability. PMID- 24242785 TI - Overdiagnosis and overtreatment of low back pain: Long-term effects. AB - Low back pain and subsequent disability remain a concern in terms of both cost and impact upon industry let alone the adverse effects on the patients involved. The causes of low back pain remain elusive. There has been extensive focus on the intervertebral disc with treatment ranging from passive modalities to multiple surgery. Current experience suggests that misinformation, inadequate patient examination, medication abuse, over use of passive modalities, focus on pain rather than function and excessive reliance on radiological imaging and specialist referrals are contributing factors. Indeed, one is drawn to the conclusion that low back disability may well be an iatrogenic disorder in many cases. PMID- 24242788 TI - Frank Ruddle (1929-2013). PMID- 24242791 TI - Casino policies: Have Australians had a fair deal? AB - The introduction of commercial casinos to Australia in 1973 was arguably the most radical shift of gambling policy in Australia's history. At one level, the risk seems to have been justified, with very little organised public opposition to the promotion of casinos as a catalyst for tourism growth and regional economic development. However, recent events suggest that Australian casino policies have moved to a more politicised stage, a period in which governments could be forced to contend with new conflicts, tensions and contradictions. Now that some of the benefits and costs of casinos have become apparent, it is appropriate to evaluate existing casino policies and trends, and to reconsider other alternatives which might be available. This paper examines the broad social implications of the Australian casino "boom," the economic changes which have occurred, and the social and political costs which have begun to surface. PMID- 24242792 TI - The cognitive psychology of gambling. AB - A number of recent studies have shown there may be a strong cognitive bias in explaining persistent gambling. Theories that have been put forward include the illusion of control, "cognitive regret," biased evaluations and the "psychology of the near miss." Two exploratory studies examining the acquisition, development and maintenance of gambling behaviour involving adolescent fruit machine gamblers were carried out. Those factors which directly relate to the cognitive biases (notably erroneous beliefs about skill) during gambling activity are discussed with reference to the above cognitive influences. PMID- 24242793 TI - Neutralizing marginally deviant behavior: Bingo players and superstition. AB - Bingo is one of the most popular and most accepted forms of gambling in the United States today. Yet, despite its popularity, many bingo players are not completely comfortable with the moral "rightness" of their actions. This participant observation and interview study spanning a 5 year period shows how bingo players use superstitious strategies, such as feelings, hunches and psi, attitudes, and luck to neutralize their marginally deviant behaviors. PMID- 24242794 TI - Federal control of Indian Lands v. State control of Gaming - Cabazon Bingo and the Indian Gaming regulatory act. AB - In September, 1988, the 100th Congress passed the Indian Gaming Regulatory Act, concluding five years of debate over the Indian Gaming issue - brought to a head by a Supreme Court decision in February, 1987, that barred states from regulating Indian Gaming. That case (State of California v. Cabazon Band of Mission Indians) forced the legislature to take a serious look at issues of gaming on Indian lands. The result was the creation of a three-tiered system whereby tribes will control ceremonial games, the federal government will control bingo, and the states and tribes will negotiate agreements to cover casino games, parimutuel racing, and jai alai, if such games are legal in that particular state. In light of the case of the Cabazon Indians and the passage of the Indian Gaming Regulatory Act, this paper will address the following competing issues: tribal sovereignty, state interests, federal interests, and states like Nevada, which have a regulated gaming industry. PMID- 24242795 TI - Market niche analysis in the casino gaming industry. AB - This article discusses the nature of market niche analysis in the casino gaming industry. It presents four approaches for conducting market niche analysis. An an example of one approach, the Las Vegas Visitor Profile Study is used to identify a premium niche in the Las Vegas Slot Target Market. A detailed examination of the premium niche profile provides a description of the typical premium slot player. The description of the typical premium player leads to hypotheses regarding needs (the unique preference set) of the premium player. An analysis of the unique preference set suggests an appropriate enhanced marketing program. PMID- 24242797 TI - Erratum. PMID- 24242796 TI - Minimal treatments and problem gamblers: A preliminary investigation. AB - In view of the increasing popularity of minimal intervention treatments for problem drinking, a self-help manual for people who wish to reduce or stop gambling was prepared. Twenty-nine (ACT residents) who responded to advertisements for help with problem gambling were allocated to either of two minimal treatments, "Manual (only)" and "Manual & Interview". On average, clients from both groups reduced the frequency of their gambling sessions, frequency of overspending, and amount spent per week in the first three months and next three months after first contact, but expenditure per session increased from three to six months, after an initial improvement. There was no evidence that a single in depth interview added to the effectiveness of the manual. PMID- 24242798 TI - Field response of maritime pine scale,Matsucoccus feytaudi duc. (Homoptera: Margarodidae), to synthetic sex pheromone stereoisomers. AB - The absolute configuration of the primary component of the maritime pine scale (Matsucoccus feytaudi) pheromone (i.e., (8E, 10E)-3,7,9-trimethyl-8,10-dodecadien 6-one) was determined as 3S,7R by field-trapping experiments using synthetic stereoisomers and according to previous NMR considerations. The 3R,7R isomer showed similar activity to 3S,7R, whereasM. feytaudi males responded very weakly to the two other candidates (3R,7S and 3S,7S). Further studies were conducted to optimize scale trapping for monitoring scale populations. Results of these studies showed that the trapping efficiency was related to pheromone dose, trap area, and wind speed but not to trap height. PMID- 24242799 TI - Ergovaline and peramine production in endophyte-infected tall fescue: Independent regulation and effects of plant and endophyte genotype. AB - Peramine and ergovaline have ecological and economical significance because they possess insect and/or mammalian toxicity properties. The relationship between these endophytically derived alkaloids in tall fescue (Festuca arundinacea Schreb.) is unknown. Seasonal and plant tissue effects on the concentration of peramine and ergovaline was investigated in field and greenhouse experiments. The relationship between the alkaloids and the regulatory effects of endophyte and plant on their content were investigated among progeny of reciprocal crosses between high- and low-ergovaline and peramine plant-endophyte combinations. Variation in peramine concentration ranged from 750 to 1742 ug/kg in greenhouse grown plants, and there was no seasonal trend in peramine content. There was a correlation (r=0.69) between peramine and ergovaline content among leaf tissues of field-grown plants, but there was no correlation between the alkaloids in the culm (r=0.20) or panicle (r=0.17) tissues. Mean leaf ergovaline concentration of progeny derived from the low-ergovaline parent (163 ug/kg) was less than the midparent value (228 ug/kg), but mean of progeny from the high-ergovaline parent was not different from the mid-parent value. Ranges within each progeny set were approximately double their mean. Mean leaf peramine concentrations of the progeny sets were similar to the mid-parent value (3354 ug/kg) but ranges were from 1716 to 8753 ug/kg. There was no correlation between leaf peramine and ergovaline (r=0.01). These data suggest that endophytically produced alkaloids are independently regulated and are controlled by both plant and endophyte genotype. PMID- 24242800 TI - Response ofMatsucoccus thunbergianae males to synthetic sex pheromone and its utilization for monitoring the spread of infestation. AB - Attraction of (2E,4E,6R,10R)-4,6,10,12-tetramethyl-2,4-tridecadien-7-one [1; (6R,10R)-matsuone] and its antipode [2; (6S,10S)-matsuone] toMatsucoccus thunbergianae males was studied in the laboratory and in the field. They showed stronger response to1. In laboratory bioassays, the threshold concentrations for male attraction with1 and2 were 16 fg and 150 pg, respectively. In the field, during the first two days after traps were set, traps baited with 50 ug of1 on rubber septa or filter paper rolls caught more males than control traps. Between the sixth day and the tenth day after traps were set, in a daily trap catch experiment, the traps with 50 ug of1 on filter paper rolls caught more males than control traps on one day only, whereas those on rubber septa were always effective. The shape of the traps did not affect male catches. Males were caught on pheromone traps in locations where no scales were found by the customary detecting procedures. PMID- 24242801 TI - Identification of branched alkanes in lipids ofLeptinotarsa decemlineata say andTribolium destructor by GC-MS: A comparison of main-beam and link-scanned spectra. AB - Branched hydrocarbons were identified in the lipids ofLeptinotarsa decemlineata Say andTribolium destructor by gas chromatography, ordinary electron impact mass spectrometry, and linked, scanned, daughterion monitoring. This methodology allowed us to revise our earlier results based only on GC-MS data confirming the existence of only monomethyl-, dimethyl-, and trimethylalkanes in the hydrocarbons ofL. decemlineata Say. The hydrocarbons fromTribolium destructor consist ofn-alkanes, 3-methylalkanes, internally branched monomethylalkanes and dimethylalkanes. Daughter-ion monitoring can be particularly important for distinguishing between incidentally overlapped GC peaks of hydrocarbons from different series. A trace, for example, of dimethylalkane coeluating withn-alkane was easily identified in GC peak of hydrocarbon mixture ofT. destructor. Link scans confirmed also molecular weights for the compounds without molecular ions in the mass spectra. Structural assignment of the compounds were verified by comparison of the experimental and calculated values of the GC retention Kovats indexes (KI). PMID- 24242802 TI - Dorsal abdominal glands in nymphs of southern green stink bug,Nezara viridula (L.) (heteroptera: Pentatomidae): Chemistry of secretions of five instars and role of (E)-4-oxo-2-decenal, compound specific to first instars. AB - We investigated the exocrine secretions from the five nymphal instars in the southern green stink bug,Nezara viridula, by analyzing separately the contents of the three dorsal abdominal reservoirs. All DAGs 1 produced a mixture of five alkanes with 12, 13, 14, 15, and 16 carbons. No differences were found between DAGs 2 and DAGs 3, for the five instars: the glands of first instars produce the same alkanes as DAGs 1,n-tridecane, traces of (E)-2-decenal, and a specific compound: (E)-4-oxo-2-decenal. In the other instars (second to fifth), (E)-4-oxo 2-decenal is absent from the secretion but another compound is present: (E)-4-oxo 2-hexenal. The kinetics of production of the different compounds were studied, the maximum amounts produced occurring 36 hr after hatching. The biological function of (E)-4-oxo-2-decenal was investigated. Using olfactometry, we showed that this compound acts as an attractant and an arrestant on second instars, at physiological doses. Moreover, this semiochemical was shown to be repellent to the fire-antSolenopsis geminata, a potential predator ofN. viridula and we established the dose-response curve for the repellent activity. PMID- 24242803 TI - Induction of parasitoid attracting synomone in brussels sprouts plants by feeding ofPieris brassicae larvae: Role of mechanical damage and herbivore elicitor. AB - Induction of plant defense in response to herbivory includes the emission of synomones that attract the natural enemies of herbivores. We investigated whether mechanical damage to Brussels sprouts leaves (Brassica oleracea var.gemmifera) is sufficient to obtain attraction of the parasitoidCotesia glomerata or whether feeding byPieris brassicae caterpillars elicits the release of synomones not produced by mechanically damaged leaves. The response of the parasitoidCotesia glomerata to different types of simulated herbivory was observed. Flight-chamber dual-choice tests showed that mechanically damaged cabbage leaves were less attractive than herbivore-damaged leaves and mechanically damaged leaves treated with larval regurgitant. Chemical analysis of the headspace of undamaged, artificially damaged, caterpillar-infested, and caterpillar regurgitant-treated leaves showed that the plant responds to damage with an increased release of volatiles. Greenleaf volatiles and several terpenoids are the major components of cabbage leaf headspace. Terpenoids are emitted in analogous amounts in all treatments, including undamaged leaves. On the other hand, if the plant is infested by caterpillars or if caterpillar regurgitant is applied to damaged leaves, the emission of green-leaf volatiles is highly enhanced. Our data are in contrast with the induction of more specific synomones in other plant species, such as Lima bean and corn. PMID- 24242804 TI - Olfactory basis of cannibalism in grasshoppers (Orthoptera: Acididae): I. laboratory assessment of attractants. AB - Two laboratory-reared and five field-collected species of grass-hoppers were assayed for behavioral responses to volatile chemicals emitted from grasshopper cadavers using a two-choice olfactometer with no stimulus as a control. Necrophilic and necrophobic responses to the stimuli were dependent upon species, sex, development, starvation, crowding, and attractant. Laboratory rearedMelanoplus differentialis (Thomas) and field-collectedHadrotettix trifasciatus (Say) andAulocara elliotti Thomas exhibited significant responses to the cadavers. Females of these three species showed significant movement towards the cadavers, but males were not significantly necrophilic. All tested developmental stages ofH. trifasciatus (fourth-instar nymphs through adults) showed significant attraction to cadavers. FedM. differentialis adults andH. trifasciatus adults and nymphs were significantly attracted to cadavers, but starved individuals were either repelled or exhibited no significant response. Although femaleA. elliotti from an uncrowded population were significantly attracted to cadavers, females from a crowded population were significantly repelled from cadavers. Contraspecific cadavers more frequently elicited a measurable response in adultM. sanguinipes andH. trifasciatus than did conspecific cadavers, and only contraspecific cadavers yielded a significant (necrophilic) response. AlthoughM. differentialis was necrophilic, neither males nor females were significantly attracted to water. PMID- 24242805 TI - Olfactory basis of cannibalism in grasshoppers (Orthoptera: Acrididae): II. field assessment of attractants. AB - The responses of rangeland grasshoppers to biologically and historically derived attractants were studied in a shortgrass prairie in southeastern Wyoming in July 1990. Seven long-chain fatty acids (C14-C20: singly and in combination), grasshopper cadavers, molasses, fruit extracts, and chloroform (solvent control) were tested. Each attractant was applied to filter paper and placed in an arena delimited by a 0.10-m(2) aluminum ring. Grasshoppers were most attracted to linoleic and linolenic acids, with significantly more grasshoppers found in these arenas than in those of the controls or other attractants. These two fatty acids alone and in combination were more attractive at 1 grasshopper equivalent (GE) than at 5 GE. The seed bug,Lygaeus kalmii Stal, and five species of ants were also attracted to these two fatty acids. Molasses had significantly more grasshoppers on the filter paper than did the other attractants, but molasses had significantly fewer grasshoppers in the arena than the fatty acids. Fruit extracts were not effective at attracting grasshoppers. Water extracts of cadavers attracted significantly more grasshoppers to the bait than did chloroform extracts. Because the assayed grasshopper community was dominated by the Gomphocerinae (a subfamily that includes many pest species that do not readily consume wheat bran bait), it may be possible to use fatty acids in conjunction with insecticidal bran baits for increased control of rangeland grasshoppers. PMID- 24242806 TI - Olfactory basis of cannibalism in grasshoppers (Orthoptera: Acrididae): III. Use of attractants on carbaryl wheat bran bait. AB - Two known necrogenic attractants, linoleic acid (18:2) and linolenic acid (18:3), were added to carbaryl bran bait to enhance control of rangeland grasshoppers in southeastern Wyoming. The primary goal was to increase control of species of Gomphocerinae, which normally do not consume bran bait. Each attractant was applied at 1, 5, and 10 grasshopper equivalents (GE) (e.g., a 1-GE treatment had the amount of fatty acid per unit weight of wheat bran that would be found in one grasshopper). Controls included carbaryl bran with no attractant and no treatment. Bran was applied at a rate of 1 kg/ha to 1-ha blocks on June 6, 1992, with four replicates per treatment and control. Plots were sampled for grasshoppers and nontarget organisms one day prior to and one, two, and three days after treatment. The addition of linoleic acid (10 GE) resulted in significantly lower total grasshopper densities than carbaryl bran alone. None of the attractants significantly improved control of all Gomphocerinae due to inconsistent effects among species. Relative to carbaryl bait alone, all doses of both fatty acids significantly improved control ofAmphitornus coloradus (Thomas). However, the attractants did not change the level of control ofCordillacris occipitalis orAulocara elliotti, and linolenic acid (5 GE) and linoleic acid (1 GE) resulted in significantly poorer control ofAgeneotettix deorum (Scudder) than carbaryl bait alone. Nontarget arthropods were largely unaffected by the attractants, except for the spiders, which were significantly reduced in all linolenic acid treatments. PMID- 24242807 TI - Allelopathic effects of phenolic mixtures on respiration of two spruce mycorrhizal fungi. AB - Investigations were conducted to determine whether the allelopathic effect (inhibition of oxygen consumption) of mull- and mor-type humic solutions on ectomycorrhizal fungi was due to the solutions' phenolic contents. In the first experiment, two concentrations (10(-3) M and 10(-7) M) of binary equimolar phenolic mixtures were tested on the oxygen consumption ofLaccaria laccata andCenococcum graniforme. The high concentrations of most of the mixtures induced an increase of fungal respiration, whereas the 10(-7) M treatments all reduced the rate of respiration. In the second experiment, the effects on respiration of the phenolic mixture reproducing mull- and mortype humic solutions were compared with the effects of natural humic solutions. The resulting data suggest that allelopathic effect of humic solutions can at least in part be attributed to their phenolic contents. PMID- 24242808 TI - Male sex pheromone of cockroachEurycotis floridana (walker) (Blattidae, Polyzosteriinae): Role and composition of tergites 2 and 8 secretions. AB - InEurycotis floridana, the male calling behavior is associated with the exposition of epidermal glands located under tergites 2, 7, and 8. 4-Hydroxy-5 methyl-3(2H)-furanone and 4-hydroxy-2,5-dimethyl-3(2H)-furanone were recently identified as the specific components of tergite 7 secretion. Methylene chloride extracts of tergite 7 and its major compound 4-hydroxy-5-methyl-3(2H)-furanone attract the conspecific females at a distance. Methylene chloride extracts of tergite 8 are also attractive at a distance to the females, whereas extracts of tergite 2 had no effect on males and females. Our GC investigations showed the absence of specific compounds in tergite 2 secretions. The GC-MS analyses revealed that the male secretion of the gland under tergite 8 is mainly a mixture of (2R*, 3R*)-butanediol, 1-dodecanol and benzyl 2-hydroxybenzoate. These compounds were tested at different concentrations on their own, or as a mixture. Only (2R*, 3R*)-butanediol and 1-dodecanol were attractive for the females. Their functions, as components of the male sex pheromone, in addition with the two derivatives of the furanone are discussed. PMID- 24242809 TI - Cuticular lipid profiles of queens, workers, and males of social waspPolistes metricus say are colony-specific. AB - The cuticular lipids ofPolistes metricus queens, workers and males from seven laboratory-maintained colonies were extracted and analyzed by combined gas chromatography-mass spectrometry. Males had higher proportions of alkenes (20.5%) in their cuticular lipids than did queens (2.3%) or workers (7.7%). Discriminant analyses of the cuticular lipid profiles of the adult wasps showed that males group separately from females. Additional analyses showed that queens group with their respective workers by colony and that queens group even more closely with males by colony. The most distinct groupings occurred with workers only by colony and with males only by colony. Stepwise discriminant analyses showed that each type of grouping was dependent upon a different combination of cuticular lipids. PMID- 24242810 TI - Sex pheromone-mediated flight and landing behaviors of the European corn borer,Ostrinia nubilalis (Hubner). AB - The pheromone-mediated flight and landing behaviors of maleOstrinia nubilalis were studied in a wind tunnel. The pheromone source was placed in the middle of an 18 * 18-cm horizontal surface, and a smaller surface placed 4, 18, or 36 cm downwind. The smaller surface did not appear to affect significantly the flight tracks or position of landing of males on the upwind surface, and it allowed the positions and altitudes of males as they passed over the downwind surface to be estimated. The flight altitude and position of males as they passed over the downwind surface related to where males landed on the upwind surface. Regardless of the downwind position of the downwind surface, most males flew over its center (i.e., in line with the source) and landed in line with the source on the upwind surface. When a small 2.5 * 10-cm vertical object was placed on the upwind surface, just upwind and to one side of the source, males flew over the downwind surface in positions skewed toward the vertical object and in broader distributions than for the comparable situation without an object: males landed on the upwind surface on positions skewed toward, or on, the object and with a broader distribution (laterally). Flight altitude also corresponded with landing position. Thus, when there was no vertical object, most males flew just above the downwind surface and landed on the downwind edge of the upwind surface. In contrast, with the vertical object, males flew significantly higher and tended to land past the downwind edge of the upwind surface. With a taller object (20 cm), males flew even higher, past the downwind edge and most landed on the vertical object. These data show the close relationship between flight and landing behaviors of maleO. nubilalis and suggest that flight maneuvers that determine track and altitude largely govern where a male lands. PMID- 24242811 TI - Up in smoke: I. Smoke-derived germination cues for postfire annual,Nicotiana attenuata torr. Ex. Watson. AB - Some postfire annuals with dormant seeds use heat or chemical cues from charred wood to synchronize their germination with the postfire environment. We report that wood smoke and polar extracts of wood smoke, but not the ash of burned wood, contain potent cue(s) that stimulate germination in the postfire annual plant,Nicotiana attenuata. We examined the responses of seeds from six populations of plants from southwest Utah to extracts of smoke and found the proportion of viable seeds that germinated in the presence of smoke cues to vary between populations but to be consistent between generations. With the most dormant genotypes, we examine three mechanisms by which smoke-derived chemical cues may stimulate germination (chemical scarification of the seed coat and nutritive- and signal-mediated stimulation of germination) and report that the response is consistent with the signal-mediated mechanism. The germination cue(s) found in smoke are produced by the burning of hay, hardwood branches, leaves, and, to a lesser degree, cellulose. Moreover, the cues are found in the common food condiment, "liquid smoke," and we find no significant differences between brands. With a bioassay-driven fractionation of liquid smoke, we identified 71 compounds in active fractions by GC-MS and AA spectrometry. However, when these compounds were tested in pure form or in combinations that mimicked the composition of active fractions over a range of concentrations, they failed to stimulate germination to the same degree that smoke fractions did. Moreover, enzymatic oxidation of some of these compounds also failed to stimulate germination. In addition, we tested 43 additional compounds also reported from smoke, 85 compounds that were structurally similar to those reported from smoke and 34 compounds reported to influence germination in other species. Of the 233 compounds tested, 16 proved to inhibit germination at the concentrations tested, and none reproduced the activity of wood smoke. By thermally desorbing smoke produced by cellulose combustions that was trapped on Chromosorb 101, we demonstrate that the cue is desorbed between 125 and 150 degrees C. We estimate that the germination cues are active at concentrations of less than 1 pg/seed and, due to their chromatographic behavior, infer that a number of different chemical structures are active. In separate experiments, we demonstrate that cues remain active for at least 53 days in soil under greenhouse conditions and that the application of aqucous extracts of smoke to soil containing seeds results in dramatic increases in germination of artificial seed banks. Hence, although the chemical nature of the germination cue remains elusive, the stability of the germination cues, their water-solubility, and their activity in low concentrations suggest that these cues could serve as powerful tools for the examination of dormant seed banks and the selective factors thought to be important in the evolution of postfire plant communities. PMID- 24242812 TI - Up in smoke: II. Germination ofNicotiana attenuata in response to smoke-derived cues and nutrients in burned and unburned soils. AB - Nicotiana attenuata is a native tobacco that is commonly found usually one growing season after fires in the blackbrush, sagebrush and pinyon-juniper forests of the Great Basin desert of North America. This plant also occurs in isolated dry washes and roadsides for many consecutive seasons. Postfire annuals are thought to synchronize their germination from the seed bank with the postfire environment in response to increases in (1) fire-related cues or (2) nutrient supply rates resulting from the mineralization of nutrients by fire, or (3) the removal of allelochemicals produced by the dominant vegetation occupying the sites before the burn or the microbial community associated with the dominant vegetation. We examine the effect of these three changes on the germination ofN. attenuata seed from artificial seed banks made with burned and unburned soil taken in 1993 from under four dominant shrub species (Coleogyne ramosissima, Yucca baccata, Lycium andersonnii, Purshia tridentata) of an area that burned in 1992 and from two dry washes in whichN. attenuata populations have persisted since at least 1988. We utilize our recent discovery that aqueous extracts of wood smoke contain potent germination cue(s) for this species and the established observation that nitrate stimulates germination in manyNicotiana species. In two experiments, we added smoke-derived germination cues and nutrients separately and in combinations to the artificial seed banks, measured germination rates, and inferred the effect of burning by the response of the seed banks to these additions. Germination rates of seed in burned soil were consistently higher than those in unburned soil collected from under all species tested; concentrations of nitrate, P, Mn, and Ca were also higher in burned than unburned soils. Because the addition of more cue and nitrate to burned soil increased germination rates, these soil components may not be at concentrations sufficient to saturate the germination response one year after a fire. The germination of seeds in soil collected from beneath unburnedYucca bacatta plants increased to the same level as that found under burned plants of the same species with the addition of cue and nitrate. Similarly, unburned bitterbrush soil attained the same germination potential with the addition of cue and a complete nutrient solution as burned bitterbrush soil. We conclude that the effect of fire on the germination potential of bitterbrush and yucca soil is due to increases in germination cue and nutrients. However, since the addition of cue and nutrients to the unburned soils under blackbrush and wolfberry shrubs did not elevate the germination potential of these soils to that found in burned soils, we conclude that these species alter the soil so as to inhibit germination and burning reverses this alteration. The presence of persistentN. attenuata populations in washes could not be attributed to particular chemical characteristics of these soils. Additions of cue dramatically increased germination potential of these soils, whereas the addition of nitrate did not. The concentrations of most mineral nutrients resembled those found in the unburned sites with the exception of Mn, Cu, and Zn, which were higher. However, these cations do not influence germination rates. Treatment of soil taken from these washes with cue resulted in significant increases in germination ofN. attenuata seeds in the natural seed bank compared to water-treated controls, demonstrating that the plants growing in washes also produce dormant seeds that require the smoke cue for germination. PMID- 24242813 TI - Distance of response to host tree models by female apple maggot flies,Rhagoletis pomonella (Walsh) (Diptera: Tephritidae): Interaction of visual and olfactory stimuli. AB - Mature female apple maggot flies,Rhagoletis pomonella (Walsh), were released individually onto a single potted, fruitless hawthorne tree in the center of an open field. The tree was surrounded by four 1-m(2) plywood host tree models painted green or white, with or without synthetic host fruit odor (butyl hexanoate), and placed at one of several distances from the release tree. Each fly was permitted to forage freely on the release tree for up to 1 hr, or until it left the tree. Flies left the tree significantly sooner when green models with host fruit were present at 0.5, 1.5, or 2.5 m distance from the release tree than when these models were placed at a greater distance (4.5 m) from the release tree or when no models were present. Flies responded detectably to 1-m(2) models without odor up to a maximum distance of 1.5 m. These results suggest that female apple maggot flies did not detect green 1-m(2) models with odor 4.5 m away or models without odor 2.5 m or more away. Flies responded to white models with and without odor to a much lesser extent, both in terms of response distance and flight to and alightment upon models. Increasing model size to 2 m(2) increased the distance to 2.5 m at which flies responded to green models without odor. Decreasing model size to 0.5 m(2) reduced fly responsiveness to green or white models. The presence of host fruit odor alone, without the visual stimulus of a green model, did not influence residence time on the release tree. PMID- 24242814 TI - Identification and synthesis of female sex pheromone of Oriental beetle,Anomala orientalis (Coleoptera: Scarabaeidae). AB - Females of the Oriental beetle,Anomala orientalis (Waterhouse), release a sex pheromone composed of a 9:1 blend of (Z)- and (E)-7-tetradecen-2-one. The double bond position of the pheromone was determined by DMDS derivatization and interpretation of the fragmentation patterns produced by monounsaturated ketones. In a sustained-flight tunnel, males responded by flying toward female beetles and attempting to copulate with them. Both effluvium and whole-body extracts of OB females were analyzed, and the activity was found only in the airborne extracts. Flight-tunnel bioassays also showed that a synthetic 90:10Z/E blend on a rubber septum was attractive and that the responses of males to this blend were equivalent toZ isomer alone, but much better than to the singleE isomer. PMID- 24242815 TI - Lipids of cyanobacteriumAphanizomenon flos-aquae and inhibition ofChlorella growth. AB - The inhibition of the growth of the green algaChlorella pyrenoidosa by the lipids of the cyanobacteriumAphanizomenon flos-aquae is associated with the fractions containing long-chain unsaturated fatty acids. A sterol present inAphanizomenon has been identified as poriferasterol. PMID- 24242816 TI - Cuticle alkanes of honeybee larvae mediate arrestment of bee parasiteVarroa jacobsoni. AB - The ectoparasitic miteVarroa jacobsoni invades worker brood cells of the honeybeeApis mellifera during the last 20 hr before the cells are sealed with a wax cap. Cuticle extracts of 8-day-old worker honeybee larvae occupying such brood cells have an arrestment effect on the mite. The mites run for prolonged periods on the extract, systematically returning onto the stimulus after touching the borders of the treated area. Mites increase walking speed and path straightness in response to increasing doses of a nonpolar fraction of the cuticle extract. Saturated straight-chain odd-numbered C19-C29 hydrocarbons were identified by thin-layer argentation chromatography and gas chromatography-mass spectrometry as the most active constituents, with branched alkanes also contributing to the arrestment effect of this active fraction. Analysis of the behavior responses to syntheticn-alkanes indicate that the response is probably based on a synergism between the different alkane components of the fraction rather than to an individual compound. PMID- 24242817 TI - Importance of phenolic glucosides in host selection of shoot galling sawfly,Euura amerinae, onSalix pentandra. AB - The effects of phenolic glucosides on the oviposition behavior ofEuura amerinae L. (Hymenoptera: Tenthredinidae) were tested in multiple oviposition experiments using different shoot length categories ofSalix pentandra L. (with different amounts of phenolic glucosides) and in experiments with pure phenolic glucosides (salidroside, arbutin, salicin, 90% salicortin, 90% 2'-O-acetylsalicortin) or composite total fractions of phenolic glucosides from three willow species (S. pentandra, S. myrsinifolia Salisb.,S. triandra L.). This was the first time that the effects of pure phenolic glucosides on the oviposition behavior of sawfly species were tested. Total fraction of phenolic glucosides fromS. pentandra and its main individual glucoside, 2'-O-acetyl-salicortin, stimulated the strongest ovipositional behavior inE. amerinae. The results show clearly that females ofE. amerinae can recognize and choose their host willow,S. pentandra, on the basis of phenolic glucosides. Moreover, they are probably able to use phenolic glucosides as a cue in shoot selection within host-plant individuals. PMID- 24242819 TI - Immunobiology of TNFSF15 and TNFRSF25. AB - TNFRSF25 is an understudied broad-acting T cell costimulator with high homology to TNFR1, however, the overall role of this receptor in T cell immunobiology is unclear. Ligation of TNFRSF25 by its monogamous ligand, TNFSF15 (TL1A), leads to recruitment of TNFR-associated factor 2 and TNFR-associated death domain in primary T cells with downstream activation of both NFkappaB as well as the PI3K/Akt axis. These signaling pathways are dependent upon coordinated engagement of the T cell receptor and interleukin-2 receptor and leads to the constitutive proliferation of CD4+FoxP3+ regulatory T cells (Treg) as a result of tonic exposure to self-antigen. Concurrent activation of CD4+ or CD8+ conventional T cell clones is dependent upon the availability of cognate foreign antigen. Here, we provide a review of both the literature and our work on this receptor and propose that the overall function of TL1A signaling to TNFRSF25 in T cells is to provide simultaneous costimulation of foreign-antigen-specific effector T cells and pre-existing Treg in order to focus the clonality of effector immunity to pathogen-derived antigens and reduce the risk of bystander inflammation toward self- or endogenous microbial antigens. PMID- 24242820 TI - American Indian perspectives on evidence-based practice implementation: results from a statewide Tribal Mental Health Gathering. AB - Implementation of Evidence-Based Practices (EBP) within American Indian and Alaskan Natives communities is currently an area of debate and contention. There is considerable concern about expanding EBP policy mandates to AI/AN communities as these mandates, either through funding restrictions or other de facto policies, recall past histories of clinical colonization and exploitation by the state and federal government. As a response, work is being done to evaluate indigenous programs and examine strategies for culturally-sensitive implementation. While the literature reflects the perspectives of AI/AN populations on EBP generally, no one has yet reported the perspectives of AI/AN communities on how to feasibly achieve widespread EBP implementation. We report the findings of a statewide Tribal Gathering focused on behavioral health interventions for youth. The Gathering participants included AI/AN individuals as well as staff working with AI/AN populations in tribal communities. Participants identified strengths and weaknesses of the five legislatively fundable programs for youth delinquency in Washington State and discussed strategies likely to be effective in promoting increased uptake within tribes. Analysis of these discussions resulted in many useful insights in program-specific and community driven strategies for implementation. In addition, two major themes emerged regarding widespread uptake: the importance of a multi-phase engagement strategy and adopting a consortium/learning community model for implementation. The findings from this Gathering offer important lessons that can inform current work regarding strategies to achieve a balance of program fidelity and cultural alignment. Attending to engagement practices at the governance, community and individual level are likely to be key components of tribal-focused implementation. Further, efforts to embed implementation within a consortium or learning community hold considerable promise as a strategy for sustainability. PMID- 24242818 TI - The evolving art of hematopoietic stem cell transplantation: translational research in post-transplant immune reconstitution and immunosuppression. AB - Allogeneic hematopoietic stem cell transplantation (SCT) offers the best chance for cure and/or long-term survival for a broad range of diseases, including many high-risk hematologic malignancies, bone marrow failure states and subsets of inherited metabolic diseases and hemoglobinopathies. Clinical advances in allogeneic SCT have resulted in dramatically improved clinical outcomes over the past two decades, resulting in a significant expansion of transplant utilization to many recipients who would previously have been excluded from consideration, including elderly recipients and individuals lacking matched sibling or unrelated donors. Despite these advances, significant clinical challenges remain, including delayed immune reconstitution and the frequent occurrence of acute and chronic graft-versus-host disease, especially in the unrelated donor transplant setting. Translational laboratory efforts, facilitated by technical advances in our ability to measure thymopoiesis and functional T cell subsets in humans, have resulted in an improved understanding of immune recovery and have provided novel insights that may lead to more rational and selective immunosuppression. PMID- 24242821 TI - Metallothioneins as dynamic markers for brain disease in lysosomal disorders. AB - OBJECTIVE: To facilitate development of novel disease-modifying therapies for lysosomal storage disorder (LSDs) characterized by nervous system involvement such as metachromatic leukodystrophy (MLD), molecular markers for monitoring disease progression and therapeutic response are needed. To this end, we sought to identify blood transcripts associated with the progression of MLD. METHODS: Genome-wide expression analysis was performed in primary T lymphocytes of 24 patients with MLD compared to 24 age- and sex-matched healthy controls. Genes associated with MLD were identified, confirmed on a quantitative polymerase chain reaction platform, and replicated in an independent patient cohort. mRNA and protein expression of the prioritized gene family of metallothioneins was evaluated in postmortem patient brains and in mouse models representing 6 other LSDs. Metallothionein expression during disease progression and in response to specific treatment was evaluated in 1 of the tested LSD mouse models. Finally, a set of in vitro studies was planned to dissect the biological functions exerted by this class of molecules. RESULTS: Metallothionein genes were significantly overexpressed in T lymphocytes and brain of patients with MLD and generally marked nervous tissue damage in the LSDs here evaluated. Overexpression of metallothioneins correlated with measures of disease progression in mice and patients, whereas their levels decreased in mice upon therapeutic treatment. In vitro studies indicated that metallothionein expression is regulated in response to oxidative stress and inflammation, which are biochemical hallmarks of lysosomal storage diseases. INTERPRETATION: Metallothioneins are potential markers of neurologic disease processes and treatment response in LSDs. PMID- 24242822 TI - Negative affectivity, emotion regulation, and coping in migraine and probable migraine: a New Zealand case-control study. AB - BACKGROUND: Migraine is a prevalent and disabling health condition. While there have been some suggestions that personality may be linked to migraine incidence, dose-response links to disability or impact are yet to be conducted and multivariate analyses are uncommon. PURPOSE: The purposes of this study are to evaluate the personality characteristics differentiating migraine and probable migraine sufferers from matched controls in multivariate models and assess the possibility of a dose-response relationship. METHODS: Fifty migraine sufferers and 50 age-, sex-, and ethnicity-matched controls in New Zealand completed personality measures including negative affectivity, coping, and monitoring blunting. RESULTS: Logistic regressions indicated that migraine status was concurrently predicted by Type D negative affectivity, more frequent venting and planning coping, and lower monitoring. There was little evidence to suggest a consistent dose-response type effect of personality on migraine; lower impact and disability were associated with greater openness to experiences, acceptance, and behavioural disengagement. CONCLUSIONS: A personality profile characterised by moderate levels of negative emotion and irritability together with failures in inhibitory self-regulation may be associated with an increased risk of strict and probable migraine. PMID- 24242824 TI - Left ventricular hypertrophy: a major factor of risk in Black hypertensive patients. PMID- 24242823 TI - Hemodynamic and echocardiographic profiles in African American compared with White offspring of hypertensive parents: the HyperGEN study. AB - BACKGROUND: Alterations in cardiovascular structure and function have been shown to precede the finding of elevated blood pressure. METHODS: This study is part of the Hypertension Genetic Epidemiologic Network (HyperGEN) in which genetic and environmental determinants of hypertension were investigated in 5 geographical field centers. All nonhypertensive offspring (n = 1,035) were included from the entire HyperGEN study population that consists of 2,225 hypertensive patients and 1,380 nonhypertensive patients who had adequate echocardiographic left ventricular (LV) mass measurements. Participants were compared by self-declared race (African American and white). RESULTS: Nonhypertensive African American offspring were younger (aged 31 years vs. 38 years), more likely to be female, and had a higher body mass index (BMI) and higher systolic blood pressure (SBP) than their white counterparts. After adjusting for age, sex, SBP, pulse pressure (PP), BMI, diabetes status, and family effects, we observed statistically significant and potentially pathophysiological differences (all with P <= 0.001) with greater LV mass/height, relative wall thickness, and posterior wall thickness and with lesser midwall shortening, PP/stroke volume, and (PP/stroke volume)/fat-free body mass. CONCLUSION: This study shows that ethnic differences in hemodynamic and echocardiographic profiles exist in a large, population-based cohort of nonhypertensive offspring of hypertensive parents. PMID- 24242826 TI - Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells. AB - This study treated the isolation and passage of muscle-derived stem cells (MDSCs) from rat penile corpora cavernosa, detection of stem cell marker expression, observation of their self-renewal and continuous proliferation, and demonstration of their potential to differentiate into smooth muscle cells in co-culture. Muscle-derived stem cells from the rat penile corpora cavernosa were isolated and purified. The expression of stem cell markers Sca-1 and desmin was detected in PP6 cells, thus confirming that the main components of PP6 cells are MDSCs. The expression of Sca-1 and desmin occurred both in PP6 cells and cells at passages 3, 6, and 8, and there was no significant decrease in the expression level with increasing passage number. The growth curves indicated that the cell doubling time was approximately 48 h. The cells entered the stationary phase after approximately 7 days of culture. The proliferative activity of the cells at passage 8 remained unchanged. After 2 days of co-culture with smooth muscle cells, the DAPI-labeled MDSCs tended to exhibit smooth muscle cell morphology and expression of alpha-SMA was detected. MDSCs exist in the rat penile corpora cavernosa and possess the potential to differentiate into smooth muscle cells. This discovery serves as the basis in view of the potential use of endogenous stem cells for the treatment of erectile dysfunction (ED). PMID- 24242827 TI - Toxic effects of resazurin on cell cultures. AB - Resazurin, introduced as a cell viability indicator under the trade name alamarBlue((r)), is generally regarded as nontoxic when used according to manufacturer's suggested shorter-term incubation time specifications. However, problems arise when exposure times are extended to longer-term cultures on the order of days. To assess the effect of resazurin over longer incubation times, MCF7 (HTB-22), MCF10A (CRL-10317), 3T3-L1 (CL-173), and D1 (CRL-12424) cultures were tested with varying amounts of resazurin over 4- and 8-day periods. MCF7, 3T3-L1, and D1 cells cultured for 8 days with 20 % alamarBlue((r)) had significantly less cell survivability. Specifically, levels of metabolic activity, deoxyribonucleic acid (DNA) concentration, and glucose consumption of the cell lines cultured for 8 days in medium with 20 % alamarBlue((r)) were significantly lower (p < 0.05) than metabolic activity, DNA concentration, and glucose consumption of MCF7 cells cultured for 8 days in medium with no alamarBlue((r)). MCF7, 3T3-L1, and D1 cells used less glucose at concentrations as low as 5 %. Data also suggests the toxic effects are more pronounced in the cancerous cell line as compared to the noncancerous cells. PMID- 24242825 TI - Acute effects of a mixed meal on arterial stiffness and central hemodynamics in healthy adults. AB - BACKGROUND: Elevated central pressures and arterial stiffness are associated with increased peripheral resistance and higher sympathetic nervous system activity. Additionally, consumption of a meal is known to be sympathoexcitatory. However, the acute effects of a meal on aortic wave reflection and stiffness are unknown. Therefore, we tested the hypothesis that aortic wave reflection and stiffness would increase after a meal. METHODS: We examined these effects using high fidelity radial arterial pressure waveforms and carotid-femoral pulse wave velocity measured noninvasively by applanation tonometry before and 60 and 180 minutes after ingestion of a liquid mixed meal (Ensure; 40% of daily energy expenditure) in 17 healthy adults (9 men/8 women; aged 29 +/- 2 years). Additionally, we measured sympathetic activity by microneurography at baseline and up to 60 minutes after the meal. RESULTS: Although sympathetic activity increased after the meal, both peripheral and central pressures were reduced at 180 minutes from baseline (all P < 0.05). Contrary to our hypothesis, augmentation index (14% +/- 3% vs. 2% +/- 3% vs. 8% +/- 3%), augmentation index normalized for heart rate (8% +/- 3% vs. -3% +/- 3% vs. 3% +/- 3%), augmented pressure (5 +/- 1 mm Hg vs. 1 +/- 1 mm Hg vs. 3 +/- 1 mm Hg), and pulse wave velocity (7.1 +/- 0.2 m/s vs. 6.7 +/- 0.2 m/s vs. 6.7 +/- 0.1 m/s) were substantially reduced at 60 and 180 minutes after the meal (all P < 0.05). CONCLUSIONS: Taken together, our results suggest that a liquid mixed meal acutely decreases central hemodynamics and arterial stiffness in healthy adults, which may be a result of meal-related increases in insulin and/or visceral vasodilation. PMID- 24242831 TI - Ion-molecule equilibria, how and why. PMID- 24242829 TI - Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells. AB - Snail1 is a transcriptional factor that plays an important role in epithelial mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as alpha-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as alpha-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells. PMID- 24242830 TI - Technical Note: Guidelines for the digital computation of 2D and 3D enamel thickness in hominoid teeth. AB - The study of enamel thickness has received considerable attention in regard to the taxonomic, phylogenetic and dietary assessment of human and non-human primates. Recent developments based on two-dimensional (2D) and three-dimensional (3D) digital techniques have facilitated accurate analyses, preserving the original object from invasive procedures. Various digital protocols have been proposed. These include several procedures based on manual handling of the virtual models and technical shortcomings, which prevent other scholars from confidently reproducing the entire digital protocol. There is a compelling need for standard, reproducible, and well-tailored protocols for the digital analysis of 2D and 3D dental enamel thickness. In this contribution we provide essential guidelines for the digital computation of 2D and 3D enamel thickness in hominoid molars, premolars, canines and incisors. We modify previous techniques suggested for 2D analysis and we develop a new approach for 3D analysis that can also be applied to premolars and anterior teeth. For each tooth class, the cervical line should be considered as the fundamental morphological feature both to isolate the crown from the root (for 3D analysis) and to define the direction of the cross sections (for 2D analysis). PMID- 24242832 TI - High accuracy measurement of isotope ratios of molybdenum in some terrestrial molybdenites. AB - The isotope ratios of molybdenum in molybdenites were studied. A special triple filament technique was used to obtain stable and lasting signals for MO(+) . There are no differences bigger than +/-0.4 parts per IO4 among four samples and the standard. PMID- 24242833 TI - Design and performance of a novel electrospray interface. AB - In this work a new electrospray system has been developed which employs heat as a means of desolvation and requires no counterflow of heated gas. This article describes the operation and performance of this device, with particular emphasis on the differences between it and those described earlier. Results are presented that illustrate the dependence of signal intensity on ion source and spray chamber temperatures and on the composition and flow rate of mobile phase into the electrospray. Results on proteins electrosprayed from aqueous solutions are presented including a bacterial protease which has a tight tertiary structure. The ability to obtain fragmentation data by collisionally induced dissociation in the interface is also discussed. PMID- 24242834 TI - Surface-induced dissociation in tandem quadrupole mass spectrometers: A comparison of three designs. AB - Three different devices that-can be used for surface-induced dissociation (SID) m tandem quadrupole instruments are compared here. The designs were compared by examining the fragmentation of several compounds including benzene, W(CO)6, and (CH3)4N(+). These studies show that SID can be readily implemented on a variety of tandem quadrupoIe instruments and that the spectra obtained with the in-line and 90 degrees instruments are similar. Evidence is presented that confirms that high average internal energies and narrow distributions of internal energy are available by this technique. Efficiencies for fragmentation of odd-electron ions are on the order of those previously reported by others. The overall SID efficiency for even-electron ions is higher than that for odd-electron ions of similar structure. PMID- 24242835 TI - a compact high pressure ion source for high and low energy collision-induced dissociation studies of cluster ions on a VG analytical ZAB-2FQ. AB - A compact, field-free high pressure ion source designed to replace, with minimum disruption, the electron impact/chemical ionization ion source of a VG Analytical ZAB-2FQ hybrid BEqQ mass spectrometer is described. This ion source may be operated at temperatures from ~40 to 250 degrees C and at pressures up to 4-5 torr and, thus, is capable of producing proton-bound cluster ions up to hexamers in good yields. Examples of high energy collision-induced dissociation, low energy collision-induced dissociation, and neutralization-reionization studies of proton-bound cluster ions produced in this source are presented. PMID- 24242836 TI - Methylene substitution reactions in a quadrupole ion trap selectivity of ethylene, ethylene oxide, and dimethyl ether reactive ions. AB - To elucidate the selectivity of methylene substitution reactions of monosubstituted and disubstituted oxyaromatic compounds in a low pressure quadrupole ion trap environment, the relative abundances of covalently bound and loosely bound adducts formed by ion/molecule reactions with ethylene (ET), ethylene oxide (ETOX), and dimethyl ether (DME) were compared. Adduct ions of all three reagent gases were formed in both a conventional ion source and a quadrupole ion trap and characterized by collisionally activated dissociation. For DME and ET, the covalently bound adducts formed at (M + 45)(+) and (M + 41)(+), respectively, are direct precursors to the methylene substitution product ions at (M + 13)(+). ETOX and ET do not demonstrate the same functional group selectivity for methylene substitution as previously observed for DME. This is attributed to differences in reaction exothermicities and competing reactions. PMID- 24242837 TI - Characterization of the dissociation behavior of gas-phase protonated and methylated lactones. AB - The dissociation behavior of gas-phase protonated and methylated four-, five-, six-, and seven-membered ring lactones, some with methyl substituents in various positions, has been characterized by using a quadrupole ion trap mass spectrometer and a triple quadrupole mass spectrometer. The energy dependence of collisionally activated dissociation pathways was determined by energy-resolved mass spectrometry, and the dissociation behavior of the various protonated lactones was compared to that observed for protonated cyclic ketones and ethers of analogous ring size. The protonated cyclic ethers and ketones predominantly dissociated via dehydration, whereas the protonated lactones dissociated via losses of an alkene, ketene, and water. The dissociation behavior of the gas phase methylated lactones formed from ion/molecule reactions with dimethyl ether ions was compared to the collisionally activated dissociation behavior of isomeric protonated methyl-substituted lactones. The methylation experiments indicated that the gas-phase addition of a methyl group may dramatically alter the favored dissociation pathways when compared to the simple protonated ions. PMID- 24242838 TI - Tandem mass spectrometry of small, multiply charged oligonucleotides. AB - Multiply charged anions derived from electrospray ionization of the sodium salts of various small oligonucleotides (n = 4-8) have been subjected to tandem mass spectrometry (MS/MS) in a quadrupole ion trap. All ions were observed to dissociate with high efficiencies even under conditions not ordinarily conducive for the observance of high MS/MS efficiency. Large fractions of the total product ion signal could be attributed to single-cleavage reactions with the parent ion charge shared among the two product ions in various combinations. In every case, the most facile reaction was observed to be the loss of the adenine anion. This reaction was then observed to be followed by cleavage of the 3' C-O bond of phosphodiester linkage of the sugar from which the adenine had been lost. PMID- 24242839 TI - Characterization of Diacylglycerylphosphocholine Molecular Species by FAB-CAD MS/MS: A General Method Not Sensitive to the Nature of the Fatty Acyl Groups. AB - The use of negative ion mode fast-atom bombardment-collision-activated dissociation-tandem mass spectrometry (FAB-CAD-MS/MS) for diacylglycerylphosphocholine molecular species determinations was investigated for 24 naturally occurring and synthetic compounds. The previously proposed method of selecting [M-15](-) as the parent ion and using the relative abundance of the carboxylate daughter ions to distinguish the positions of esterification was found to be unreliable in cases where the fatty acyl group at sn1 was much larger than that at sn2. The predicted greater abundance of the sn2 carboxylate daughter, relative to the sn1 carboxylate daughter, was also violated when polyunsaturated fatty acyl groups were esterifred at sn2. In addition, several marginal cases were found where the ratio of intensities of the sn2/sn1 carboxylate daughters followed the expected pattern (sn2 > sn1) initially, but reversed over extended scanning time. The use of an alternative FAB-CAD-MS/MS method is proposed where the [M-B6](-) ion is selected as the precursor and the relative intensities of the daughters resulting from loss of the free fatty acids at snl and sn2 are determined. In every case examined to date, the ion formed by loss of the free acid from the sn2 position was always more abundant. Because the parent ion is equivalent to the phosphatidic acid ion, this technique should be equally applicable to all other phospholipid classes where this fragment ion is present in the spectrum. PMID- 24242840 TI - Theoretical calculations of relative ion yields for glow discharge mass spectrometry. AB - Quantitative determination of the elemental composition of metals and other solids by glow discharge mass spectrometry requires a calibration factor for each element. In past work, these factors, called relative ion yields (RIYs), have been determined experimentally from the mass spectra of standards of certified composition. The RlYs of some elements were found to be over 10 times larger than the RIYs of other elements. In this study a simple calculation of the RIYs of the elements within the same sample is derived from a theoretical framework which takes into account the combined effects of sputtering and ionization. The ionization function involves the electron affinity and the first ionization potential of each element, plus two unknown parameters. By favorable selection of a temperature parameter and a chemical-potential parameter, the RIYs calculated by this method were found to agree satisfactorily with the experimental RlYs of former work. The temperature of 16,000 K (used in this work) corresponds to an average electron energy of ~ 2 eV. PMID- 24242841 TI - Alternating RF/DC Isolations for Quantitation with Coeluting Internal Standards in Gas Chromatography/Ion Trap Mass Spectrometry. AB - A new ion trap scan function for gas chromatography/mass spectrometry (GC/MS) quantitation is described that employs alternating mass-selective storage (rf/dc isolation) of ions from an analyte and its coeluting isotopically labeled internal standard. This scan includes two separate ionization/isolation/mass analysis sequences within the same scan function, each optimized for either the analyte or the internal standard. This results in alternating between analyzing the analyte and the internal standard during their coelution. The method is conceptually similar to using two different scan functions to analyze either the analyte or the internal standard in alternating scans; however, it is much faster because it eliminates the slow procedure of continuously downloading alternating scan functions from disk. This allows more data points to be obtained over a GC peak, resulting in more reproducible GC peak profiles as well as better sensitivity and precision. Results of calibration curves spanning four orders of magnitude (0.5 pg to 5 pg injected on column) obtained by using this method give excellent linear correlations (r (2) > 0.9990) and precision (relative standard deviations of triplicate injections < 10%). PMID- 24242843 TI - Efficacy of metabolic surgery on HbA1c decrease in type 2 diabetes mellitus patients with BMI <35 kg/m2--a review. AB - High glycated hemoglobin A1c (HbA1c) is strongly correlated with developing type 2 diabetes mellitus (T2DM) complications; this study reviews the efficacy of various types of metabolic surgeries in reducing HbA1c levels in type 2 diabetics with BMI <35 kg/m(2). An electronic search of MEDLINE databases using terms 'metabolic surgery', type 2 diabetes mellitus, BMI <35 kg/m(2), and related keywords for studies published between 1987 and 2013. Data from 53 articles with 2,258 patients were selected for this review. The weighted mean change in HbA1c was -2.8 % (95 % CI -2.8 to -2.7, p < 0.01) and weighted mean BMI change was -5.5 kg/m(2) (95 % CI -5.6 to -5.4, p < 0.01). There was a strong correlation between weighted percentage mean change in HbA1c and BMI. Adjustable gastric banding and duodenal jejunal bypass were inferior to other surgeries in reducing BMI and HbA1c in BMI <35 kg/m(2). Metabolic surgery significantly decreases HbA1c in T2DM patients with BMI <35 kg/m(2) and that the magnitude of HbA1c change may be a useful surrogate of DM control. PMID- 24242845 TI - Letter to the editor. PMID- 24242844 TI - Predictors of weight loss are different in men and women after sleeve gastrectomy. AB - BACKGROUND: Weight loss following bariatric surgery varies according to patient factors before the intervention. However, whether predictors of weight loss differ between men and women is, to our knowledge, unknown. We therefore aimed to investigate baseline predictors for overall weight loss and identify potential sex-specific baseline predictors in bariatric surgery patients. METHODS: In this prospective cohort study, 160 patients (117 women and 43 men) who underwent sleeve gastrectomy were followed up for 2 years. Weight loss was defined as percent excess body mass index loss (%EBMIL). To investigate whether %EBMIL differed between men and women, we included all two-way interactions with sex by incorporating the product term sex and predictors using multiple linear regression analysis. RESULTS: The overall mean +/- standard deviation of %EBMIL after 2 years was 78.3 +/- 23.5. Predictors for lower %EBMIL in a regression model with no interactions were female sex (P = 0.003), higher body mass index before surgery (P = 0.001), and nonsmoking (P = 0.029). When examining sex specific predictors for %EBMIL, higher age (P = 0.027) and not having diabetes (P = 0.007) predicted lower %EBMIL in men. In women, unemployment (P = 0.006) and anxiety and/or depression (P = 0.009) predicted lower %EBMIL. CONCLUSIONS: This study suggests that weight loss and predictors for weight loss 2 years after sleeve gastrectomy are sex-specific. These findings may be useful for the surgical strategy used to treat these patients. PMID- 24242847 TI - Alpha and lineage C betaCoV infections in Italian bats. AB - AlphaCoV and lineage C betaCoV, genetically similar to those identified in Spanish related bat species, have been detected in Italian Myotis blithii and Eptesicus serotinus, respectively, out of 75 anal swabs collected from Vespertilionidae between 2009 and 2012. Sequence analysis of the 816-bp obtained RdRp sequence fragment indicates a 96.9 % amino acid identity of the Italian lineage C betaCoV with the recent Middle East Respiratory Syndrome Coronavirus (MERS-CoV, Genbank accession number KF192507). This is the first documented occurrence of a lineage C betaCoV in the Italian bat population, notably in E. serotinus. PMID- 24242846 TI - Genomic characterisation of Felis catus papillomavirus 4, a novel papillomavirus detected in the oral cavity of a domestic cat. AB - Three papillomaviruses (PVs) from the domestic cat have been fully sequenced so far including Felis domesticus PV-1 (FdPV-1), FdPV-2, and a recently described Felis catus PV-3 (FcaPV-4). In the current article, we describe the full genomic sequence of a fourth PV from the domestic cat. This PV was amplified from the oral cavity of a cat with severe gingivitis. However, the aetiological involvement of FcaPV-4 in development of lesions observed in this cat remains uncertain. The complete genome of the novel virus comprised 7,616 bp and was predicted to encode five early (E1, E2, E4, E6 and E7) and two late (L1 and L2) genes, with the organisation typical for PVs. The L1 showed 65.1 % nucleotide sequence identity to L1 of FcaPV-3 and approximately 60 % identity to L1 of canine tau-papillomaviruses CPV-2 and CPV-7. The novel virus clustered with FcaPV 3, CPV-2 and CPV-7 on a phylogenetic tree constructed from a concatenated alignment of 3,013 bp from E1, E2, L1 and L2. Based on the genomic and phylogenetic data, we propose that the novel virus is classified as a distinct species within the same genus as FcaPV-3. We also propose that both viruses are classified within the genus Taupapillomavirus, although this classification may need to be re-visited after more tau-PV genomes become available. PMID- 24242848 TI - The outcome of pulmonary resection for invasive fungal infection complicating haematological malignancy. AB - OBJECTIVES: The aim of this study was to clarify clinical outcomes of pulmonary resection of invasive fungal infection (IFI) complicating haematological malignancy. METHODS: Between 1985 and 2010, 28 patients underwent 31 pulmonary procedures for IFI complicating haematological malignancy. Retrospective chart review was performed. Seventeen patients underwent therapeutic resection and 11 patients underwent diagnostic biopsy. Survival and progression of fungal infection were analysed with the Kaplan-Meier method and prognostic factors were analysed with the Cox proportional hazards model. RESULTS: The median follow-up was 9.5 months (range 0-139 months). The rate of operative complications is significantly higher in the therapeutic resection group (P=0.036) in multivariate analysis. Median survival was 12 and 5 months in the diagnostic and therapeutic group, respectively. In the diagnostic group, 10 patients (91%) survived surgery and were cured of fungal infection; the management was changed based on biopsy in 3 patients (27.3%), and preoperative anaemia (P=0.044) adversely affected survival in multivariate analysis. In the therapeutic group, anaemia (P=0.018) and perioperative transfusion (P=0.038) adversely affected survival following therapeutic resection in univariate analysis. The rate of fungal progression in the therapeutic group was 29.4%. In multivariate analysis, only presence of bilateral lesions (P=0.0005) was a significant factor of fungal progression after therapeutic resection. CONCLUSIONS: Diagnostic biopsy contributes to good diagnostic yield with long-term cure from fungal infection. The long-term outcome (overall survival) of diagnostic and therapeutic patients relied on the severity of anaemia, which appears related to underlying haematological diseases. Presence of bilateral lesions was a significant factor of fungal progression after therapeutic resection. PMID- 24242849 TI - The risk of bilobectomy compared with lobectomy: a retrospective analysis of a series of matched cases and controls. AB - OBJECTIVES: Bilobectomy is considered to be a risky procedure due to space mismatch between the pleural space and the remnant lung. The objective of this study was to evaluate if postoperative complications related or not to size mismatch are more frequent after bilobectomy compared with right lobectomy cases. METHODS: Retrospective case-control study on a series of matched non-small-cell lung cancer patients. Cases were patients who underwent right bilobectomy (upper and middle or lower and middle) and controls, patients who underwent right upper or lower lobectomy. Cases and controls were matched by propensity scoring according to site, age, ppoFEV1, type of postoperative management (intensive physiotherapy or not), cardiac comorbidity and pT status. We selected two primary outcomes for comparison: occurrence of any cardiorespiratory complication and occurrence of any complication related to space discrepancies. For the latter, all complicated case records were reviewed and two blinded observers agreed on the probability of each complication to be related to space discrepancies. Agreement was measured by the kappa statistic. The overall odds ratio (OR) and 95% confidence interval (CI) for each outcome were calculated on 2 * 2 tables for the whole population and for cases with upper or lower resections. RESULTS: The study included 689 patients: 572 right lobectomy (419 upper and 153 lower) and 117 bilobectomy cases (30 upper and middle and 87 lower and middle). The overall mortality rate of the series was 2.03% (14/689), and cardiorespiratory complications were recorded in 14.4% (99/689) and space-related complications in 19.59% (135/689) cases. Both observers agreed on space-related complications in 86% of the 135 cases (kappa: 0.72). After matching, 234 cases entered the study (117 with right lobectomy, including 83 lower and 34 upper, and 117 with bilobectomy, including 87 lower and 30 upper). The prevalence of cardiorespiratory complications was higher after lower and middle lobectomy compared with lower lobectomy (P = 0.0002; OR: 7.96, 95% CI: 2.19-43.16). No differences were found in death rates or in space-related complications between groups of lobectomy and bilobectomy cases. CONCLUSIONS: This study failed to demonstrate a higher space-related complication rate in bilobectomy cases but cardiorespiratory complications were statistically higher after lower and middle lobectomy compared with lower lobectomy in matched cases. PMID- 24242850 TI - The role of repairing lung lacerations during video-assisted thoracoscopic surgery evacuations for retained haemothorax caused by blunt chest trauma. AB - OBJECTIVES: Retained haemothorax and pneumothorax are the most common complications after blunt chest traumas. Lung lacerations derived from fractures of the ribs are usually found in these patients. Video-assisted thoracoscopic surgery (VATS) is usually used as a routine procedure in the treatment of retained pleural collections. The objective of this study was to find out if there is any advantage in adding the procedure for repairing lacerated lungs during VATS. METHODS: Patients who were brought to our hospital with blunt chest trauma were enrolled into this prospective cohort study from January 2004 to December 2011. All enrolled patients had rib fractures with type III lung lacerations diagnosed by CT scans. They sustained retained pleural collections and surgical drainage was indicated. On one group, only evacuation procedure by VATS was performed. On the other group, not only evacuations but also repair of lung injuries were performed. Patients with penetrating injury or blunt injury with massive bleeding, that required emergency thoracotomy, were excluded from the study, in addition to those with cardiovascular or oesophageal injuries. RESULTS: During the study period, 88 patients who underwent thoracoscopy were enrolled. Among them, 43 patients undergoing the simple thoracoscopic evacuation method were stratified into Group 1. The remaining 45 patients who underwent thoracoscopic evacuation combined with resection of lung lacerations were stratified into Group 2. The rates of post-traumatic infection were higher in Group 1. The durations of chest-tube drainage and ventilator usage were shorter in Group 2, as were the lengths of patient intensive care unit stay and hospital stay. CONCLUSIONS: When compared with simple thoracoscopic evacuation methods, repair and resection of the injured lungs combined may result in better clinical outcomes in patients who sustained blunt chest injuries. PMID- 24242852 TI - Editorial: A new title and co-sponsor for the journal. PMID- 24242851 TI - Seven nonsynonymous SNPs in the gene encoding human deoxyribonuclease II may serve as a functional SNP potentially implicated in autoimmune dysfunction. AB - Many nonsynonymous SNPs in the human DNase II gene (DNASE2), potentially relevant to autoimmunity in conditions such as rheumatoid arthritis, have been identified, but only limited population data are available and no studies have evaluated whether such SNPs are functional. Genotyping of all the 15 nonsynonymous human DNase II SNPs was performed in three ethnic groups including 16 different populations using the PCR-restriction fragment length polymorphism technique. A series of constructs corresponding to each SNP was examined. Fifteen nonsynonymous SNPs in the gene, except for p.Val206Ile in a Korean population, exhibited a mono-allelic distribution in all of the populations. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, four activity-abolishing and five activity-reducing SNPs were confirmed to be functional. The amino acid residues in activity-abolishing SNPs were conserved in animal DNase II. All the nonsynonymous SNPs that affected the catalytic activity of human DNase II showed extremely low genetic heterogeneity. However, a minor allele of seven SNPs producing a loss-of-function or extremely low activity-harboring variant could serve as a genetic risk factor for autoimmune dysfunction. These functional SNPs in DNASE2 may have clinical implications in relation to the prevalence of autoimmune diseases. PMID- 24242853 TI - Addiction to fruit machines: A preliminary study among young males. AB - Although most sources treat gambling as an adult phenomenon, adolescent gambling is more widespread than is generally recognized, and in some cases may even be pathological. This paper outlines a preliminary study of eight adolescents addicted to playing and gambling on coin-in-the-slot machines (more commonly known as 'fruit machines'). Factors involved in the onset of fruit machine playing are examined along with their alternative gambling activities and associated problems. The role of 'skill' and 'excitement' components in persistent playing are also discussed. PMID- 24242854 TI - Street crime, tourism and casinos: An empirical comparison. AB - Only recently have researchers begun to study the "causes" of crime in tourist destinations, particularly in those areas which offer casino gaming. Critics, who cite the high crime rates of Atlantic City, New Jersey and Las Vegas, Nevada, fail to understand the relationship between tourism and crime. Casino gaming is a catalyst for tourism and one of the social consequences of tourism is increased crime.The mean crime rates of three tourist areas (including Atlantic City) and two urban centers in New Jersey were examined to determine if the rates were significantly different. Additionally, the study examined and identified which types of crime have changed since the advent of tourism in Atlantic City.Policy makers who reject gaming in favor of other mechanisms for urban revitalization need to take note. Tourist destinations have mean crime rates significantly different (higher) from urban areas, at least in New Jersey. Gaming-free tourism initiatives will have similar consequences for a community, as gaming has been identified to have had on Atlantic City. PMID- 24242855 TI - Is excessive gambling seen as a form of dependence? Evidence from the community and the clinic. AB - Data from two studies are used to examine the proposition that excessive gambling, unlike excessive substance use, is not generally viewed as a form of dependence. In the first study, the attitudes of 100 members of the general population towards the causes of excess and towards appropriate treatments, indicated that excessive gambling was seen in more moral terms than were other addictive behaviours. In the second study, of 54 people receiving treatment for one of four forms of excessive behaviour, gamblers were just as likely to use terms such as 'addiction' or 'compulsion' to describe their behaviour but were also more likely than others to describe it in terms of moral weakness or vice. Concern is expressed at the way in which gambling may be marginalized as a form of dependence. PMID- 24242856 TI - A review of two measures of pathological gambling in the United States. AB - This paper addresses a debate that has emerged in the field of pathological gambling research. This debate concerns measurement of the prevalence of pathological gambling in the general population. Two instruments have been used to measure prevalence in the United States, the South Oaks Gambling Screen and the Cumulative Clinical Signs Method. These instruments are described and several problems with the statistical properties of the Cumulative Clinical Signs Method are discussed. The authors conclude with a call for continued research in the area of prevalence studies of pathological gambling. PMID- 24242857 TI - Demographic, personality, cognitive and behavioral correlates of off-course betting involvement. AB - A large (n=381) exploratory survey of off-course bettors was conducted as a step towards rectifying deficits in current gambling literature. Information collected by interviews and questionnaires from off-course betting agency customers showed the level of betting involvement to be largely unrelated to demographic and cognitive variables and sensation seeking, but related to a variety of betting behaviors. A factor analysis produced three independent factors accounting for 30% of the variance. Loadings on these suggested an independence of items involved in the process of betting and those related to the control of betting behaviors, implying that non-pathological gambling involvement may be a reasonable goal for treatment programs. PMID- 24242859 TI - Hereditary pancreatitis: dilemmas in differential diagnosis and therapeutic approach. AB - INTRODUCTION: Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common PRSS1 mutations worldwide are the R122H and N29I variants. CLINICAL FEATURES: HP usually appears with an acute, a recurrent acute, and a chronic phase, referring to the inflammation of the pancreas and the symptoms' onset and duration. The clinical features of acute pancreatitis begin in childhood and last less than 6 months. HP carries a 50-70-fold increased risk of pancreatic cancer within 7-30 years of disease onset. HP diagnosis is defined by the presence of a detected cationic trypsinogen gene mutation (with or without clinical or radiological manifestations of chronic pancreatitis) or when the patient's family satisfies the requirements of the EUROPAC. TREATMENT: With regard to the therapeutic approach, pancreatic enzyme replacement therapy and analgesics are offered to control pain. In addition, endoscopic and surgical intersections are reserved for all relevant complications. Unfortunately, surgical removal of affected pancreatic tissue does not necessarily guarantee the patient's long-term survival. Furthermore, the prognostic factors and the efficacy of extended resection remain controversial. PMID- 24242858 TI - Definition and usage of the term "overuse injury" in the US high school and collegiate sport epidemiology literature: a systematic review. AB - BACKGROUND: A number of epidemiologic and surveillance-based studies of sports injury provide statistics on, and sometimes discussion of, overuse injuries. However, there is no consensus on the definition of "overuse." Some studies consider "overuse" as a mechanism of injury while others use a diagnosis-based definition. OBJECTIVE: The objective of this study was to describe variation between studies in the definition and use of the term "overuse." METHODS: PubMed and SPORTDiscus databases were searched between May and November 2012 to find articles published or online ahead of printing pertaining to US high school or collegiate athletics, which were epidemiologic in nature. Inclusion criteria required that the article present data collected on athlete exposure and provided statistics pertaining to overuse injuries. PRISMA guidelines were adhered to, to the best ability of the authors. RESULTS: The initial search resulted in 5,182 articles with potential for inclusion. After review of titles or abstracts where appropriate, 232 studies were read in entirety to determine if they were appropriate for inclusion. Of the 35 articles included, 13 used data from the National Collegiate Athletics Association's Injury Surveillance System, 12 used data from the High School Reporting Information Online (RIO) injury surveillance system, and one used data from both of these systems. The remaining nine articles used data from distinct surveillance systems or prospectively collected data. All of these articles included data on overuse injuries, although not all provided definitions for overuse. A major finding from the literature is that the term "overuse" has been used both as a mechanism of injury and as an injury diagnosis (or a category of diagnoses). Specifically, of 35 articles, 14 used "overuse" as a mechanism of injury, seven used it as a category of injury diagnoses, eight used it as both a category of injury diagnoses and a mechanism of injury, and it was unclear in one how the term is used. Only one of the 35 articles provided a biomechanical definition for overuse injuries. Twelve of 35 articles combined "overuse" with other terms such as "chronic," "gradual onset," and "repetitive stress." Use of the term "no contact" was investigated in relation to "overuse." Four of 35 articles define overuse in the context of no contact injuries. Only one of 35 articles define "no contact" as a specific acute mechanism of injury, while all other mentions of "no contact" do not specifically distinguish whether "no contact" was limited to acute injuries only, or has potential to include "overuse" injuries. CONCLUSION: There is a great deal of inconsistency in the use of the term "overuse" both within and between data sources. This is further complicated by the multiple uses of the term "no contact." We recommend that the term "overuse" only be used in regard to the mechanism of injury in order to enhance interpretation and understanding of the literature regarding overuse injuries and enhance the ability to compare results between studies. We also recommend the adoption of a common working definition of overuse injuries within injury surveillance. This definition should emphasize that overuse injuries are characterized by (1) a mechanism of gradual onset, and (2) an underlying pathogenesis of repetitive microtrauma. PMID- 24242860 TI - An interesting clinical entity of squamous cell cancer of the pancreas with liver and bone metastases: a case report and review of the literature. PMID- 24242863 TI - Editorial comment. PMID- 24242864 TI - Demonstration of an actuarial method for estimating preinjury hand strength. AB - Assessments of the magnitude of performance loss caused by injury or disease necessarily involve a comparison of a person's performance before and after the onset of impairment. Well-established procedures are available for measuring current performance on a variety of evaluation instruments. However, few actuarial methods have been developed for estimating the person's performance prior to injury. This study demonstrated how regression equations can be used to estimate preinjury hand strength. Although the equations generated in this investigation are specific to hand strength, the methodology can be extended to estimate the preinjury performances of persons with a variety of physical and intellectual impairments. PMID- 24242862 TI - Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors. AB - BACKGROUND: Anti-angiogenic therapies such as bevacizumab upregulate hypoxia inducible factor-1alpha (HIF-1alpha), a possible mechanism of drug resistance. Camptothecin analogues, including SN-38, have been shown to reduce the expression and transcriptional activity of HIF-1alpha in preclinical models. We hypothesized that co-administration of pegylated SN-38 (EZN-2208) may offset the induction of HIF-1alpha following bevacizumab treatment, resulting in synergistic antitumor effects. PATIENTS AND METHODS: Patients with refractory solid tumors were enrolled. Objectives were to evaluate the modulation of HIF-1alpha protein and target genes in tumor biopsies following administration of the combination of EZN 2208 administered weekly * 3 (days 1, 8, 15) and bevacizumab administered every 2 weeks, in 28-day cycles, and to establish the safety and tolerability of the combination. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were obtained following bevacizumab alone (before EZN-2208) and after administration of both study drugs. RESULTS: Twelve patients were enrolled; ten were evaluable for response. Prolonged stable disease was observed in 2 patients, one with HCC (16 cycles) and another with desmoplastic round cell tumor (7 cycles). Reduction in HIF-1alpha protein levels in tumor biopsies compared to baseline was observed in 5 of 7 patients. Quantitative analysis of DCE-MRI from 2 patients revealed changes in K(trans) and k(ep). The study closed prematurely as further clinical development of EZN-2208 was suspended by the pharmaceutical sponsor. CONCLUSION: Preliminary proof-of-concept for modulation of HIF-1alpha protein in tumor biopsies following administration of EZN-2208 was observed. Two of 10 patients had prolonged disease stabilization following treatment with the EZN-2208 and bevacizumab combination. PMID- 24242861 TI - A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma. AB - BACKGROUND: DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with >=1 prior tyrosine kinase inhibitor. METHODS: In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1-4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints. RESULTS: 35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient's tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate. CONCLUSIONS: AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine. PMID- 24242865 TI - Physical and psychosocial correlates of test-retest isometric torque variability in patients with chronic low back pain. AB - Variability in trunk torque production has been suggested as a means of detecting submaximal effort in the assessment of chronic low back pain. Several investigations question the validity of using torque variability to detect submaximal efforts in patients with back injuries. However, few investigations have studied the correlates of text-retest torque variability in clinical populations. The present study investigated psychological distress, disability/flexibility/pain, and symptom magnification correlates of test-retest torque variability in chronic low back pain patients. Contrary to previous studies, psychological distress, tendency to report symptoms, and pain were negatively correlated with measures of torque variability. The findings indicate the potential for psychological variables to influence torque production, but on the whole provide little strong support for the use of test-retest torque variability as a means of detecting submaximal performance. PMID- 24242866 TI - An identification of low back pain groups using biobehavioral variables. AB - A multivariate predictive model of low back pain (LBP) was developed. Following a semi-structured interview, 73 participants were assigned to dysfunctional chronic low back pain (DCLBP), functional chronic low back pain (FCLBP), acute low back pain (ALBP), and healthy control (HC) groups. All participants underwent a comprehensive physical, psychophysiological, and psychological evaluation. Multivariate analyses indicated no psychophysiological, few physical, and many psychological differences among the groups. The DCLBP group was found to be most impaired in flexion (p<.001), and the HC group performed the most total work (ft lb) in extension (p<.001). Psychologically, the DCLBP group displayed greater levels of emotional distress and characterological disturbances and were more functionally impaired (p<.001). Few differences between FCLBP and HC were found. A classification analysis using physical and psychological variables correctly classified 83.3% of DCLBP patients, and it was found that the ALBP group was heterogeneous with some patients having a dysfunctional profile and other patients having a functional profile. The psychological variables were more potent predictors of group membership than were the physical variables. These findings indicate that potential DCLBP and FCLBP patients can be identified shortly following an injury, suggesting important implications for assessment and treatment of low back pain in general, and more specifically, for reducing health care costs and human suffering. PMID- 24242867 TI - A strategy for evaluating occupational risk factors of musculoskeletal disorders. AB - There is a large and increasing incidence of work-related muscoloskeletal disorders, both upper extremity cumulative trauma disorders and low back pain. Several occupational risk factors have been linked with the development of musculoskeletal disorders. In order to identify the known occupational risk factors associated with a specific job, an analysis procedure is described to help identify ergonomic risk factors in the workplace. Job analysis should be one part of an overall ergonomics control program. Once the ergonomic risk factors have been documented, the ergonomics committee can use that information to begin developing solutions that will decrease or eliminate the identified risk factors. When placing a worker who is returning to the workforce after recovering from an injury, health care professionals can also use the information from the job analysis to assist in matching up task demands with worker capabilities and limitations. PMID- 24242868 TI - The role of onion-associated fungi in bulb mite infestation and damage to onion seedlings. AB - In Israel Rhizoglyphus robini is considered to be a pest in its own right, even though the mite is usually found in association with fungal pathogens. Plant protection recommendations are therefore to treat germinating onions seedlings, clearly a crucial phase in crop production, when mites are discovered. The aim of this study was to determine the role of fungi in bulb mite infestation and damage to germinating onion seedlings. Accordingly we (1) evaluated the effect of the mite on onion seedling germination and survival without fungi, (2) compared the attraction of the mite to species and isolates of various fungi, (3) assessed the effect of a relatively non-pathogenic isolate of Fusarium oxysporum on mite fecundity, and (4) determined the effects of the mite and of F. oxysporum separately and together, on onion seedling germination and sprout development. A significant reduction of seedling survival was recorded only in the 1,000 mites/pot treatment, after 4 weeks. Mites were attracted to 6 out of 7 collected fungi isolates. Mite fecundity on onion sprouts infested with F. oxysporum was higher than on non-infested sprouts. Survival of seedlings was affected by mites, fungi, and their combination. Sprouts on Petri dishes after 5 days were significantly longer in the control and mite treatments than both fungi treatments. During the 5-day experiment more mites were always found on the fungi infected sprouts than on the non-infected sprouts. Future research using suppressive soils to suppress soil pathogens and subsequent mite damage is proposed. PMID- 24242869 TI - Stable isotope analyses reveal dense trophic species packing and clear niche differentiation in a Malagasy primate community. AB - Understanding the mechanisms maintaining local species richness is a major topic in tropical ecology. In ecological communities of Madagascar, primates represent a major part of mammalian diversity and, thus, are a suitable taxon to study these mechanisms. Previous research suggested that ecological niche differentiation facilitates the coexistence of lemurs. However, detailed data on all species making up diverse local primate assemblages is rarely available, hampering community-wide tests of niche differentiation among Malagasy mammals. Here, we took an indirect approach and used stable isotopes as long-term indicators of individuals' diets to answer the question of whether trophic patterns and food-related mechanisms stabilize coexistence in a species-rich lemur community. We analyzed stable carbon and nitrogen isotopes in hair collected from eight syntopic lemurs in Kirindy Forest. We found that lemur species were well separated into trophic niches and ranged over two trophic levels. Furthermore, species were densely packed in isotopic space suggesting that past competitive interactions between species are a major structuring force of this dry forest lemur community. Results of other comparative studies on primates and our findings underline that-in contrast to communities worldwide-the structure and composition of lemur communities follow predictions of ecological niche theory. Patterns of competitive interactions might be more clearly revealed in Malagasy primate communities than elsewhere because lemurs represent a large fraction of ecologically interacting species in these communities. The pronounced trophic niche differentiation among lemurs is most likely due to intense competition in the past as is characteristic for adaptive radiations. PMID- 24242870 TI - Physiological functions of endoplasmic reticulum stress transducer OASIS in central nervous system. AB - Eukaryotic cells can adapt to endoplasmic reticulum (ER) dysfunction by producing diverse signals from the ER to the cytosol or nucleus. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins: double stranded RNA-dependent protein kinase (PKR)-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6). These ER stress transducers basically play important roles in cell survival after ER stress. Recently, novel types of ER stress transducers that share a region of high sequence similarity with ATF6 have been identified. They have a transmembrane domain, which allows them to associate with the ER, and possess a transcription-activation domain and a basic leucine zipper (bZIP) domain. These membrane-bound bZIP transcription factors include OASIS, BBF2H7 CREBH, CREB4 and Luman, and are collectively referred to as OASIS family members. Despite their structural similarities with ATF6, differences in activating stimuli and tissue distribution indicate specialized functions of each member on regulating UPR signaling in specific organs and tissues. One of them, OASIS, is expressed preferentially in astrocytes in the central nervous system (CNS). OASIS temporally regulates the differentiation from neural precursor cells into astrocytes to promote the expression of Glial Cell Missing 1 through dynamic interactions among OASIS family members followed by accelerating demethylation of the Gfap promoter. This review is a summary of our current understanding of the physiological functions of OASIS in the CNS. PMID- 24242871 TI - Morphological variations of the vallate papillae in some mammalian species. AB - The morpho-structural characteristics of the vallate papillae of the tongue of rat, dog, donkey and buffalo were investigated by macroscopy and their microstructure by light and scanning electron microscopy (SEM). The numbers of vallate papillae varied among the different species. In rat, a single vallate papilla surrounded by incomplete groove and an annular fold was observed. Taste buds were detected along the entire length of the medial and lateral groove epithelium, but not in the papillary dome. In dog, some papillae lacking the annular pad had irregular ridges and grooves toward the center of the papillary surface, while other papillae had small secondary papillary grooves arising from the center of the papilla. Taste buds were located in the medial and lateral epithelium of both primary and secondary grooves as well as in the dome epithelium. In donkey, two papillae were frequently observed around the midline of the tongue root, and an additional papilla was found occasionally in the middle and associated with secondary papilla. In buffalo, several papillae were relatively small and variable in shape. With SEM, small ridges and grooves were found in the papillae of donkey and buffalo. In both species, taste buds were constantly observed along the medial wall epithelium, but no taste buds were found in the lateral wall. We conclude that the vallate papillae exhibited peculiar characteristics, which are species specific and might have a correlation with the variable feeding habits among these animals. PMID- 24242873 TI - Post-mortem changes in chemical profile and their influence on corpse removal in ants. AB - In order to decrease the risk of pathogen transmission, ants remove corpses from the vicinity of nests, but little is known about the underlying mechanisms. In particular, it is unclear how the odor profile of corpses changes with time since death and how any changes might relate to behavior. We have addressed these questions in the red ant Myrmica rubra, where we asked how the time since death determines the ability of workers to discriminate a dead individual from a live one, and whether dead workers are removed in a similar way when they originate from the same or an alien colony. We found that ants could discriminate alien from nestmate corpses up to 2 days after death, since the former continued to elicit aggressive behavior over that period. For dead nestmates, only 15 % of corpses were removed when freshly killed but this rises to 80 % for corpses between 1 to 6 days post mortem. Using gas chromatography, we found that oleic and linoleic acids, which are absent on freshly killed corpses, appeared post mortem and were in higher quantities on those corpses that were ejected from the nest vicinity. When added to fresh corpses, linoleic and oleic acids, alone or blended, enhanced removal to levels observed for corpses of 2-6 days post-mortem. Thus, oleic and linoleic acids appear to be important cues involved in corpse recognition and necrophoresis over a long timeframe, and we advance the hypothesis that these fatty acids in combination with other cues may also trigger other behaviors such as prey retrieval. PMID- 24242876 TI - Reactions of strong bases with vinyl fluoride formation and characterization of 1 fluorovinyl anion and the fluoride-acetylene hydrogen-bonded complex. AB - Vinyl fluoride reacts with strong bases to afford I-fluorovinyl anion (1a) and a fluoride-acetylene cluster (1b). The former ion can be prepared independently, and cleanly, by the fluorodesilylation of 1-(trimethylsilyl) fluoroethylene. Reactions of 1a are reported, and its proton affinity is assigned (387 +/- 3 kcal mol(-1)). Vinyl fluoride is 22 kcal mol(-1) more acidic than ethylene. This unusually large substituent effect is reproduced by ab initio calculations, and can be accounted for by geometric changes which minimize the electron-electron repulsion in 1a. Computations on 2-fluorovinyl anions (1c and 1d) have also been carried out, and both ions are only slightly less stable than 1a. The cis isomer (1c) has a larger barrier for fluoride elimination and is a reasonable target for preparation. PMID- 24242874 TI - Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice. AB - Sorafenib--a broad kinase inhibitor--is a standard therapy for advanced hepatocellular carcinoma (HCC) and has been shown to exert antifibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia--and its consequences on treatment resistance--remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1 alpha (SDF-1alpha) expression in cancer and stromal cells and, subsequently, myeloid differentiation antigen positive (Gr-1(+)) myeloid cell infiltration. The SDF-1alpha/C-X-C receptor type 4 (CXCR4) pathway directly promotes hepatic stellate cell (HSC) differentiation and activation through the mitogen-activated protein kinase pathway. This is consistent with the association between SDF-1alpha expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF-1alpha increased the survival of HSCs and their alpha-smooth muscle actin and collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1(+) myeloid cells mediate HSC differentiation and activation in a paracrine manner. CXCR4 inhibition, using AMD3100 in combination with sorafenib treatment, prevents the increase in tumor fibrosis--despite persistently elevated hypoxia--in part by reducing Gr-1(+) myeloid cell infiltration and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibits HCC growth when combined with sorafenib treatment. CONCLUSION: Blocking SDF-1alpha/CXCR4 or Gr 1(+) myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment. PMID- 24242875 TI - Interleukin-7 receptor single nucleotide polymorphism rs6897932 (C/T) and the susceptibility to systemic lupus erythematosus. AB - Emerging evidences were accumulated to support the view that aberrant interleukin 7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P = 0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P = 0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P = 0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene. PMID- 24242877 TI - Fragmentation of 1- and 3-methoxypropene ions another part of the C4H 8O (+*) potential energy surface. AB - The fragmentation mechanisms of metastable ionized 1- and 3-methoxypropene have been examined in detail by using ionization and appearance energy measurements, metastable ion and collisional activation mass spectra, and a variety of isotopically labeled molecules. These metastable C4H8O(+*) ions fragment by loss of H; CH3, and H2CO, and the experimental observations allowed the construction of the potential energy diagram which describes their interconversion and the participation of four other distonic and carbene C4H8O(+*) ions. It was found that these two methyl alkenyl ether ions had no common reaction channel with either the 2-methoxy isomer or with any of the alcohol, keto, or enol C4H8O(n+*) isomers which previously have been extensively studied. PMID- 24242872 TI - The dynamic architectural and epigenetic nuclear landscape: developing the genomic almanac of biology and disease. AB - Compaction of the eukaryotic genome into the confined space of the cell nucleus must occur faithfully throughout each cell cycle to retain gene expression fidelity. For decades, experimental limitations to study the structural organization of the interphase nucleus restricted our understanding of its contributions towards gene regulation and disease. However, within the past few years, our capability to visualize chromosomes in vivo with sophisticated fluorescence microscopy, and to characterize chromosomal regulatory environments via massively parallel sequencing methodologies have drastically changed how we currently understand epigenetic gene control within the context of three dimensional nuclear structure. The rapid rate at which information on nuclear structure is unfolding brings challenges to compare and contrast recent observations with historic findings. In this review, we discuss experimental breakthroughs that have influenced how we understand and explore the dynamic structure and function of the nucleus, and how we can incorporate historical perspectives with insights acquired from the ever-evolving advances in molecular biology and pathology. PMID- 24242878 TI - Organic neutralization agents for neutralization-reionization mass spectrometry. AB - Porter has shown that excited neutrals of specified internal energies can be prepared by neutralization of an ion beam with metal vapors of low ionization potential (IP). For specific problems in neutralization-reionization mass spectrometry, a metal with the desired IP value may not be available, or it may present experimental problems such as a high vaporization temperature, instrument contamination, or detector instability. The use of organic neutralization agents such as tetra-p-anisylethylene (IP = 6.0 eV) can minimize these problems (although cross sections for neutralization with these are a factor of 5 lower than those with metals), and can provide a much wider range of IP values. Their utility is demonstrated in the neutralization of C4H4 (+*) and CH8 (+*) ions to produce C4H4 and C4H8 of selected internal energies. However, for CH4 (+*) neutralization, the CH4 neutrals formed have a much lower internal energy than predicted, indicating that electron transfer from the neutralization agent predominantly produces its ions in excited states. PMID- 24242879 TI - m-nitrobenzyl alcohol electrochemistry in fast atom bombardment mass spectrometry. AB - The efficacy of m-nitrobenzyl alcohol (NBA) as a solvent (matrix) for fast atom bombardment (FAB) mass spectrometry of a group of pyrazolate-bridged dirhodium A frame complexes has been assessed. Although NBA is frequently used to mitigate the formation of artifacts in FAB/MS of organometallics and other materials susceptible to bombardment-induced reactions, substantial evidence indicates that such reactions cause the formation of artifacts in the spectra obtained here. Parallel absorption spectroscopic studies have established that NBA is capable of inducing both oxidation and reduction reactions independent of ion bombardment, depending on analyte reduction half-wave potential (E1/2). From the known electrochemistry of the complexes studied, it can be estimated that 1020 mV > E1/2 > 500 mV for the reaction of NBA serving as a reducing agent, while 500 mV > E1/2 > 424 mV for the reduction potential of NBA. However, in the presence of bombardment the former E1/2 must be at least as low as 356 mY, and the latter E1/2 must be at least as high as 1188 mY. The kinetics of redox reactions involving NBA, and therefore their influence on the appearance of FAB mass spectra, will be highly sample-dependent. However, this study illustrates an important potential role for redox reactions when NBA is used as a solvent, especially in the presence of bombardment in FAB/MS. Although analyte reaction products could be identified, substantial efforts aimed at identifying NBA oxidation and reduction products did not yield any definitive results due to the complexity of product mixtures. PMID- 24242880 TI - A glow discharge ion source with fourier transform ion cyclotron resonance mass spectrometric detection. AB - A glow discharge (CD) ion source has been coupled to a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer using a four-element electrostatic lens to accelerate and focus ions generated external to the instrument's high magnetic field into its analyzer cell. Like other CD mass spectrometers, GD-FT ICR can provide a quantitative measure of bulk analyte concentration with good precision and accuracy. Although detection limits currently attainable are several orders of magnitude higher than the commercially available magnetic sector-based instrument, CD-FT-ICR holds promise for ultrahigh resolving power elemental mass analysis. Several schemes are proposed to lower the detection limits of the technique while still providing high enough resolution to resolve isobaric interferences. PMID- 24242881 TI - Selection of solvent load and first-stage pressure to reduce interference effects in inductively coupled plasma-mass spectrometry. AB - In inductively coupled plasma-mass spectrometry the first-stage pressure and solvent characteristics can strongly influence spectral and nonspectroscopic interference effects. By manipulating the pressure and solvent load, one can regulate the degree of analyte signal suppression observed in the presence of high concentrations (> 10 mM) of concomitants. Importantly, the same operating conditions that eliminate the matrix effects maintain the analytical utility of the system. However, for some interferent-analyte combinations, the identity of the concomitant anion and subsequent pH of the solution determine whether the interference effects can be eliminated entirely. The first-stage pressure does not appear to significantly affect the oxide-ion and doubly charged ion ratios; the solvent characteristics are the dominant factors that dictate these ratios. PMID- 24242882 TI - Nanoscale separations combined with electrospray ionization mass spectrometry: Sulfonamide determination. AB - Nanoscale capillary liquid chromatography (nCLC) and capillary zone electrophoresis (CZE) have been combined with quadrupole mass spectrometry via an electrospray ionization (ESI) interface. These methodologies have been applied to the separation and determination of a variety of sulfonamides. CZE/ESI/MS is the more rapid and sensitive technique, but nCLC/ESI/MS shows promise for the analysis of dilute samples. Ultimately, the two techniques provide complementary methods of analysis. The detection limits of these techniques in the full-scan mode are in the low picomole range. Dissociation of the sulfonamides can be induced by increasing the skimmer voltage. This provides a limited means of discriminating between compounds of identical molecular weight but, more important, provides fragments that could be used to confirm the presence of analyte within a sample. PMID- 24242883 TI - Collision-induced dissociation mass spectrometry of nonionic surfactants following direct supercritical fluid injection. AB - Direct injection from a capillary supercritical fluid chromatography system was used as an inlet technique for chemical ionization (CI) and low energy collision induced dissociation (CID) mass spectrometry of a series of low volatility nonionic surfactant mixtures. Characteristic fragment ions produced by CID for various classes of nonionic surfactant molecules were found to depend greatly on the structure of the surfactant hydrophobe. This was the case even when the charge on the molecule appeared localized away from the hydrophobe. Numerous decomposition pathways are suggested by the fragment ions produced. The use of direct supercritical fluid injection as an inlet technique does not appear to influence adversely the ability to produce cm mass spectra. Direct supercritical fluid introduction allows CI to be compared with other ionization mechanisms more commonly used for multifunctional, low volatility samples. PMID- 24242884 TI - Generation of substructure identification rules using feature-combinations from tandem mass spectra. AB - Software to interpret tandem mass spectra, entitled Method for Analyzing Patterns in Spectra (MAPS), has been developed to provide substructure information for an automated compound identification system, This software consists of several program modules which manipulate databases of tandem mass spectra and substructure information, generate substructure identification rules, and apply these rules to the tandem mass spectra of unknown compounds to identify components of their structure. The MAPS rule generation program has been modified to generate rules based on specific combinations of spectral features that occur concertedly. False positives are drastically reduced by searching for "feature combinations" that have 100% uniqueness with respect to a reference database of compounds. Recall is increased by the determination of multiple feature combinations indicative of the presence of a given substructure. Strategies were developed in the algorithm for the discovery of feature-combinations that avoid the computation "explosion" that occurs when working with a large number of spectral features. The rules developed have the form: "IF feature-eombination a (FC a) or FC b,..., or FC x, THEN substructure SSn is present." PMID- 24242885 TI - Evaluation of automatically generated substructure identification rules from tandem mass spectra. AB - Substructure identification rules for phenothiazine and barbiturate substructures were generated by using a new version of the Method for Analyzing Patterns in Spectra (MAPS) software. This software uses tandem mass spectra and known substructure content of reference compounds to provide "feature-combination" rules. A feature-combination is a series of tandem mass spectral features which are completely unique to compounds containing a specified substructure. The current reference databases contain over 11,000 daughter spectra of 100 compounds acquired at two different collision gas pressures (i.e., single- and multiple collision conditions). The results of rule evaluation procedures are presented and include a comparison of the spectral features developed in rule generation to those identified in documented fragmentation pathways of the indicated substructure. Two potential sources of error due to spectral feature and substructure "cross-correlation" were identified. If errors occur, they can be detected by calculating cross-correlation coefficients and edited from the rules. A beneficial cross-correlation involving feature-combinations was also discovered. The rules obtained by using single- and multiple-collision data were further evaluated by applying them to tandem mass spectra of 20 test compounds (compounds not in the reference database). The results of these evaluations give a good indication of the utility of the rules for use in an automated structure elucidation system for tandem mass spectrometry data. PMID- 24242887 TI - NF-kappaB2/p100 deficiency impairs immune responses to T-cell-independent type 2 antigens. AB - Formation of the splenic marginal zone (MZ) depends on the alternative NF-kappaB signaling pathway. Recently, we reported that unrestricted activation of this pathway in NF-kappaB2/p100-deficient (p100(-/-) ) knock-in mice alters the phenotype of MZ stroma and B cells. Here, we show that lack of the p100 inhibitor resulted in an expansion of both MZ B and peritoneal B-1 cells. However, these cells failed to generate proliferating blasts in response to T-cell-independent type 2 (TI-2) Ags, correlating with dampened IgM and absent IgG3 responses. This phenotype was in part due to increased activity of the NF-kappaB subunit RelB. Moreover, p100(-/-) ->B6 BM chimeras were more susceptible to infection by encapsulated Streptococcus pneumoniae bacteria, pathogens that induce TI-2 responses. In contrast to the TI-2 defect, p100 deficiency did not impair immune responses to the TI-1 Ag LPS and p100(-/-) MZ B cells showed normal Ag transportation into B-cell follicles. Furthermore, p100(-/-) MZ B and B-1 cells failed to respond to TI-2 Ags in the presence of WT accessory cells. Thus, NF kappaB2/p100 deficiency caused a predominant B-cell-intrinsic TI-2 defect that could largely be attributed to impaired proliferation of plasmablasts. Importantly, p100 was also necessary for efficient defense against clinically relevant TI-2 pathogens. PMID- 24242888 TI - Are divided attention tasks useful in the assessment and management of sport related concussion? AB - This article is a systematic review of the literature on divided attention assessment inclusive of a cognitive and motor task (balance or gait) for use in concussion management. The systematic review drew from published papers listed in PubMed, MEDLINE, EMBASE and CINAHL databases. The search identified 19 empirical research papers meeting the inclusion criteria. Study results were considered for the psychometric properties of the paradigms, the influence of divided attention on measures of cognition and postural control and the comparison of divided attention task outcomes between individuals with concussion and healthy controls (all samples were age 17 years or older). The review highlights that the reliability of the tasks under a divided attention paradigm presented ranges from low to high (ICC: 0.1-0.9); however, only 3/19 articles included psychometric information. Response times are greater, gait strategies are less efficient, and postural control deficits are greater in concussed participants compared with healthy controls both immediately and for some period following concussive injury, specifically under divided attention conditions. Dual task assessments in some cases were more reliable than single task assessments and may be better able to detect lingering effects following concussion. Few of the studies have been replicated and applied across various age groups. A key limitation of these studies is that many include laboratory and time-intensive measures. Future research is needed to refine a time and cost efficient divided attention assessment paradigm, and more work is needed in younger (pre-teens) populations where the application may be of greatest utility. PMID- 24242889 TI - Sport-related concussions: a review of epidemiology, challenges in diagnosis, and potential risk factors. AB - Sport-related concussion (SRC) is a common mild traumatic brain injury among young, active individuals, affecting approximately 300,000 young American adults annually. In this review of the epidemiology of SRC, we describe the challenges in identifying concussion occurrence and review the studies describing concussion incidence in various sports. In high risk contact sports, American football, soccer (European football), hockey, lacrosse, and basketball athletes experience concussion unintentionally during the course of play. Among these, football concussion incidence is reviewed in greatest detail because it has the highest incidence among the contact sports, and some studies have shown long-term neurophysiologic and neurodegenerative outcomes. Mechanisms of injury differ significantly by sport and can be potential targets for concussion risk mitigation. Despite the apparent high incidence of SRC, risk factors determining initial concussion, recovery periods, recurrence, and long-term outcomes remain poorly understood and warrant further study exploring the influence of age, sex, genetics, and athletic factors. PMID- 24242891 TI - 180 W vs 120 W lithium triborate photoselective vaporization of the prostate for benign prostatic hyperplasia: a global, multicenter comparative analysis of perioperative treatment parameters. AB - OBJECTIVE: To evaluate the surgical performance of the new Greenlight XPS-180 W laser system (American Medical Systems, Minnetonka, MI) and the effect of prostate volume (PV), in comparison with the former HPS-120 W system, for the treatment of benign prostatic hyperplasia by photo-selective vaporization of the prostate. METHODS: Between July 2007 and March 2012, 1809 patients underwent laser photo-selective vaporization of the prostate (1187 patients with the use of HPS-120 W and 622 patients with the use of XPS-180 W) at 7 international centers. All data were collected prospectively. Comparative analysis was performed between XPS and HPS according to PV measured by transrectal ultrasound. RESULTS: The XPS compared with HPS, allowed significantly reduced laser and operative time (29.6 minutes vs 65.8 minutes and 53 minutes vs 80 minutes, respectively; P <.01 for both). The number of fiber used during the procedures was significantly reduced with the XPS system (1.11 vs 2.28; P <.01), whereas total energy delivered was lower (250.2 kJ vs 267.7 kJ; P = .043). Overall, the mean operative time, mean laser time, and mean energy were all significantly increased according to PV >80 mL vs <80 mL. However, when stratified according to PV, XPS demonstrates significant advantages compared with HPS, regardless of prostate size in all operative parameters (P <.01). CONCLUSION: The new XPS-180 W system exhibits significant advantages in all surgical parameters compared with the HPS-120 W system. Overall, with XPS-180 W and HPS-120 W, mean operative time, laser time, and energy usage increased according to PV. This suggests that preoperative evaluation of PV by transrectal ultrasound should be mandatory. PMID- 24242892 TI - Prostatic elasticity: a new non-invasive parameter to assess bladder outlet obstruction caused by benign prostatic hyperplasia (a canine experiment). AB - OBJECTIVE: To evaluate the change of prostatic elasticity during the development of benign prostatic hyperplasia (BPH) and its correlation with the degree of bladder outlet obstruction (BOO) in the canine model of BOO caused by BPH. MATERIALS AND METHODS: Ten male beagle dogs were selected in this study. To establish canine model of BOO caused by BPH, each beagle underwent castration surgery followed by encapsulating the prostate with a double layer of nylon mesh and then treating the beagles with a combination of steroids for 12 weeks. Transrectal ultrasound (TRUS) examination and urodynamic evaluation were performed before and at 4, 8, and 12 weeks of hormone administration. Prostatic volume, Young modulus of prostatic tissue, and urodynamic parameters were compared at each time instance, and the correlation between the Young modulus of the prostatic tissue and urodynamic parameters were evaluated. RESULTS: All beagles developed BOO caused by BPH over the time period of the study. Prostatic volume, Young modulus of prostatic tissue, and urodynamic parameters had statistically significant differences before and after 4, 8, and 12 weeks of hormone administration (P <.05). Young modulus of prostatic tissue showed a very significant correlation with urodynamic parameters, including maximum urine flow (Qmax) (r = -0.802, P <.01), Qave (r = -0.711, P <.01), Pves@open (r = 0.638, P <.01), Pves@Qmax (r = 0.699, P <.01), Pdet@Qmax (r = 0.757, P <.01), and Pdetmax (r = 0.739, P <.01). CONCLUSION: Young modulus of prostatic tissue increased during the development of the BPH. There was a significant correlation between Young modulus of prostatic tissue and the degree of BOO. PMID- 24242890 TI - Vertical distribution of ammonia-oxidizing archaea (AOA) in the hyporheic zone of a eutrophic river in North China. AB - Nitrification plays a significant role in the global nitrogen cycle, and this concept has been challenged with the discovery of ammonia-oxidizing archaea (AOA) in the environment. In this paper, the vertical variations of the diversity and abundance of AOA in the hyporheic zone of the Fuyang River in North China were investigated by molecular techniques, including clone libraries, phylogenetic analysis and real-time polymerase chain reaction. The archaeal amoA gene was detected in all sediments along the profile, and all AOA fell within marine group 1.1a and soil group1.1b of the Thaumarchaeota phylum, with the latter being the dominant type. The diversity of AOA decreased with the sediment depth, and there was a shift in AOA community between top-sediments (0-5 cm) and sub-sediments (5 70 cm). The abundance of the archaeal amoA gene (1.48 * 107 to 5.50 * 107 copies g-1 dry sediment) was higher than that of the bacterial amoA gene (4.01 * 104 to 1.75 * 105 copies g-1 dry sediment) in sub-sediments, resulting in a log10 ratio of AOA to ammonia-oxidizing bacteria (AOB) from 2.27 to 2.69, whereas AOB outnumbered AOA in top-sediments with a low log10 ratio of (-0.24). The variations in the AOA community were primarily attributed to the combined effect of the nutrients (ammonium-N, nitrate-N and total organic carbon) and oxygen in sediments. Ammonium-N was the major factor influencing the relative abundance of AOA and AOB, although other factors, such as total organic carbon, were involved. This study helps elucidate the roles of AOA and AOB in the nitrogen cycling of hyporheic zone. PMID- 24242894 TI - The acquisition, development, and maintenance of fruit machine gambling in adolescents. AB - In the U.K., the major commercial gambling activity in adolescents is the playing of slot machines (commonly known as "fruit machines"). Over the past few years, the negative effects of "fruit machine addiction" have been reported by various helping organizations (e.g. Gamblers Anonymous) and the national press, including allegations of attempted murder, suicide and prostitution as well as a wider incidence of petty crime.Fifty adolescent fruit machine players from a 'user population' participated in a face-to-face interview and questionnaire study examining factors in the acquisition, development and maintenance of gambling behaviour. Nine adolescent males were deemed to be pathological gamblers as measured by the American Psychiatric Association DSM-III-R diagnostic criteria, and a number of serious consequences were reported including gambling debts, truancy and stealing. PMID- 24242893 TI - Chronic escitalopram treatment induces erectile dysfunction by decreasing nitric oxide bioavailability mediated by increased nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. AB - OBJECTIVE: To investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on erectile and penile vascular function in the rat. METHODS: The effect of chronic treatment with escitalopram (0.286 mg/kg/day) on change in intracavernosal pressure, maximum intracavernosal pressure/mean arterial pressure, and area under the intracavernosal pressure curve in response to cavernosal nerve stimulation was measured. The effect of chronic escitalopram treatment on endothelial-dependent relaxant responses was investigated in isolated mesenteric and internal pudendal resistance arteries. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and nitric oxide synthase levels were determined with enzymatic assay and Western blot, respectively. RESULTS: Chronic treatment with escitalopram resulted in a significant reduction in the erectile response to cavernosal nerve stimulation without an effect on the response to intracavernosal injection of the nitric oxide donor sodium nitroprusside. The decrease in erectile function was associated with marked increases in NADPH oxidase activity in the corpora cavernosa. Treatment with escitalopram also caused a significant reduction in the relaxant response to acetylcholine in isolated internal pudendal and mesenteric resistance arteries without altering the response to sodium nitroprusside. The decreased response to acetylcholine in the isolated vascular segments was associated with a marked increase in NADPH oxidase activity that was corrected by treatment with the NAPDH oxidase inhibitor apocynin. CONCLUSION: The inhibitory effects of escitalopram on erectile and vascular function were not accompanied by a change in endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase expression, or endothelial nitric oxide synthase activity, suggesting that the inhibitory effect is caused by a decrease in nitric oxide bioavailability mediated by increased NADPH oxidase and reactive oxygen species production. PMID- 24242896 TI - Gambling in the Netherlands: Developments, participation, and compulsive gambling. AB - An inventory was made of the developments in what the gambling market had to offer and the extent of public participation in games of chance in The Netherlands for the period 1945-1988. Both these aspects show a sharp rise in the post-war years, but the more negative effects of gambling are also becoming clearer. Since the beginning of the 1980's, assistance organizations have received increasing requests for help and advice on gambling problems. Roughly half of those seeking help are younger than 25 years, presenting the compulsive use of slot-machines as their main problem. PMID- 24242895 TI - The emergence of Dutch casinos: A case study of mismarketing? AB - Ostensibly, the approval of legalized casino type gambling in the Netherlands was intended to combat illegal and uncontrolled gambling. Very early on, however, the plan conceived and implemented by the Netherlands Parliament demonstrated serious mismarketing strategies and tactics. The new legal casinos were appealing to people other than those engaged in illegal gambling, in particular foreign tourists and local "high rollers." This paper attempts to analyze the ultimate process of goal displacement, as the state casino industry allowed economic objectives to supplant desires to utilize legal casinos primarily as controls over illegal gambling. PMID- 24242897 TI - "The words of my mouth, and the meditation of my heart": The mindset of gamblers revealed in their language. AB - The colorful language of gambling and gaming is essential to creating the players' world; in analyzing it we understand that world. This fringe vocabulary or slanguage is examined in connection with standard language, and is analyzed for its origins, its humor, and for the attitudes it expresses and transmits. This language is seen as a neglected indicator ofl'histoire de mentalite, the mindset of gamblers. It is also suggested that other factors-body language, paralanguage, stock expressions composed of standard words (jokes, catch phrases, etc.)-hold clues to the outlook, superstitions, behavior, the rational and irrational beliefs of gamblers. PMID- 24242898 TI - The impact of the daily lottery on the numbers game: Does legalization make a difference? AB - There has been a profusion of state run legal lotteries over the last two decades. One justification for them has been their supposed diversion of funds from illegal games known as numbers, policy and bolita. Records obtained in a police raid in south Florida provided an opportunity to analyze the impact of Florida' legal lottery on its illegal counterpart. The records ranged over a 13 week period encompassing five weeks prior to the inception of Florida's legal daily numbers and lotto games and seven weeks afterward. While there was a 17 percent decline in monies wagered on the illegal games during the first week of the legal games, illegal wagers quickly rebounded to prelegalization levels. PMID- 24242899 TI - Tissue hypoxia in autoimmune brain disease: a Columbian discovery? PMID- 24242900 TI - Clinical outcomes of stenting for colorectal obstruction at a tertiary centre. AB - PURPOSE: Self-expandable metal stents (SEMS) have been used to manage large bowel obstruction as a palliative treatment or to initially decompress the colon as a bridge to definitive surgery. Our goal was to review clinical outcomes in patients undergoing placement of a SEMS for colorectal obstruction at a tertiary care hospital. METHODS: A retrospective review was done of patients undergoing placement of a colorectal SEMS at a single centre between August 2005 and March 2011 for obstructing lesions. Outcomes identified included clinical relief of obstruction, successful bridging to surgery or palliation, and stent-related complications. RESULTS: SEMS were placed in a total of 58 patients. The intent of stenting was to bridge to definitive surgery in 11 patients and palliation in 47 patients. Stent placement was clinically successful in relieving obstruction without early complication in 45 (78%) patients. Of the patients intended to bridge to surgery, 7/11 (64%) were successfully bridged to surgery. One patient suffered a perforation, two failed to relieve obstruction, and one re-obstructed. Of the patients stented for palliation, 32/47 (68%) were successfully palliated at a mean follow-up of 7.5 months. Five patients had perforations, six re obstructed, two had stent migration, and two failed to relieve obstruction. The overall rates for perforation, re-obstruction, and stent migration were 10, 12, and 7%, respectively. CONCLUSION: SEMS placement as a bridge to surgery and for palliation of colorectal obstruction is associated with moderate rates of clinical success but a high rate of perforation. PMID- 24242901 TI - Induced neural lineage cells as repair kits: so close, yet so far away. AB - Transdifferentiation or direct reprogramming of somatic cells into neural lineage cells has provided an invaluable new tool to advance the regenerative neural medicine. Here, we provide an overview of the various strategies currently available for producing of induced neural lineage cells in vitro as well as the direct reprogramming of neural cells in vivo. We also discussing some of the challenges faced in harnessing the potential of induced neural lineage cells for biomedical applications. PMID- 24242902 TI - Safety, tolerability, and pharmacokinetics of the novel alphav-integrin antibody EMD 525797 (DI17E6) in healthy subjects after ascending single intravenous doses. AB - PURPOSE: We evaluated the safety, tolerability, and pharmacokinetics (PK) of EMD 525797 (DI17E6), a humanized monoclonal antibody targeting alphav-integrins, in healthy subjects. METHODS: In this first-in-human, double-blind, placebo controlled, randomized Phase 1 study, healthy male volunteers were consecutively assigned to 6 ascending single-dose cohorts of 35, 100, 250, 500, 1000, or 1500 mg. Per dose cohort, EMD 525797 or placebo was administered over 1 h as an intravenous 250-mL infusion to 6 and 3 volunteers, respectively. Escalation to the next dose level was based on evaluation of safety, tolerability, and PK data. RESULTS: Fifty-five subjects (aged 18-45 years) were randomized. Twenty-seven of 37 (73 %) subjects receiving EMD 525797 reported a total of 61 adverse events (AEs), including 38 events (in 17 subjects) considered by the investigator to be treatment related. A total of 35 AEs were reported by 14 of 18 (78 %) placebo treated subjects. The most commonly occurring AEs were gastrointestinal disorders, abnormal laboratory values, and increased or decreased biochemistry and/or hematology values, as well as headaches, which occurred at a slightly higher frequency in the EMD 525797 group compared with placebo. There were no serious AEs or deaths. EMD 525797 PK appeared to be dose dependent, especially at lower doses. CONCLUSION: Ascending single doses of EMD 525797 were shown to be safe and well tolerated. No safety concerns were identified. This study supports the ongoing investigation of EMD 525797. PMID- 24242904 TI - Introductory statement. PMID- 24242903 TI - Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single-Center, Phase I, Randomized, Four-Way Crossover Study. AB - The aim of this study was to evaluate the effects of subcutaneous pasireotide on cardiac repolarization in healthy volunteers. Healthy volunteers were randomized to one of four treatment sequences (n = 112) involving four successive treatments in different order: pasireotide 600 ug (therapeutic dose) or 1,950 ug (maximum tolerated dose) bid by subcutaneous injection (sc), placebo injection and oral moxifloxacin. Maximum DeltaDeltaQTcI occurred 2 hours post-dose for both doses of pasireotide. Mean DeltaDeltaQTcI was 13.2 milliseconds (90% CI: 11.4, 15.0) and 16.1 milliseconds (90% CI: 14.3, 17.9) for the 600 and 1,950 ug bid doses, respectively. Maximal placebo-subtracted change in QTcI from baseline for moxifloxacin was 11.1 (90% CI: 9.3, 12.9) milliseconds. Both pasireotide doses caused a reduction in heart rate: maximal heart rate change compared with placebo occurred at 1 hour for pasireotide 600 ug bid and at 0.5 hours for pasireotide 1,950 ug bid, with heart rate reductions of 10.4 and 14.9 bpm, respectively. At the therapeutic dose of 600 ug, pasireotide has a modest QT-prolonging effect. The relatively small increase of ~3 milliseconds in DeltaDeltaQTcI in the presence of a 3.25-fold increase in dose suggests a relatively flat dose-effect relationship of pasireotide on DeltaDeltaQTcI in healthy volunteers. No safety concerns for pasireotide were identified during the study. PMID- 24242905 TI - Rotamer-specific fluorescence quenching in tyrosinamide: Dynamic and static interactions. AB - We have examined the environments of the three phenol rotamers about the C(alpha) C(beta) bond in tyrosinamide by fluorescence quenching. Steady-state acrylamide quenching yields a nonlinear stern-Volmer plot. With three distinct emitting species and no other information about the system, it is impossible to analyze the data due to the number of variables which have to be determined. We therefore reduced the number of variables by independently determining the fractional intensity and dynamic quenching constant for each rotamer through time-resolved fluorescence quenching studies. These parameters were then used to analyze the steady-state data for any contribution of static quenching. We conclude that the nonlinear Stern-Volmer plot for the quenching of tyrosinamide by acrylamide is a consequence of each rotamer having a distinct dynamic quenching constant and the presence of static quenching. The static quenching can be represented by either the sphere-of-action model involving two of the three rotamers or the ground state complex model involving all three rotamers. PMID- 24242906 TI - Distribution of separations between groups in an engineered calmodulin. AB - An engineered calmodulin (VU-9-CaM) has been prepared in which a tryptophan group is present at position 99 and a tyrosine at position 138. The tyrosine was converted to nitrotyrosine. Timedomain dynamic fluorescence measurements were made of energy transfer from the tryptophan donor to the nitrotyrosine acceptor. These were analyzed to yield the parameters characterizing the distribution of separations between the two groups, which are located on Ca(2+)-binding domains III and IV. Their mean separation is in reasonable agreement with the crystallographic value. PMID- 24242907 TI - Fluorescence anisotropy decay study of self-association of bacterial luciferase intermediates. AB - The fluorescence dynamics parameters of the fluorescent transient flavin luciferase species from the typesVibrio fischeri andPhotobacterium leiognathi are presented. The fluorescence anisotropy decay is a single exponential function for both types. The correlation time is 70 ns for theP. leiognathi fluorescent transient intermediate (2 degrees C, aqueous buffer, pH 7.0), consistent with the rotational correlation time of the luciferase macromolecule (77 kD) to which the flavin fluorophore is rigidly attached. In contrast, for theV. fischeri species the observed correlation time for the anisotropy decay function is 133 ns. This suggests that protein self-association occurs in theV. fischeri case and this is confirmed by filtration, where the fluorescent transient fromV. fischeri does not pass through a 100,000 molecular weight cutoff membrane, whereas theP. leiognathi species does. The filtration method also demonstrates self-association in the luciferase peroxyflavin and photoflavin fromV. fischeri. A monomer-dimer equilibrium also explains the previously reported high correlation times for theV. harveyi luciferase-flavin species. It is proposed that the self-association competes with the lumazine protein interaction in the bioluminescence reaction. PMID- 24242908 TI - Continuous lifetime distributions of beta-cyclodextrin-anilinonaphthalene sulfonic acid inclusion complexes. AB - Fluorescence lifetimes are reported for a series of anilinonaphthalene sulfonate (ANS) probe molecules complexed with beta-cyclodextrin (beta-CD). The fluorescence decay kinetics are recovered by multifrequency phase and modulation measurements in concert with a global analysis scheme. In all cases studied, a continuous Lorentzian distribution of lifetimes is observed, resulting from the dynamical nature of the ANS-beta-CD complex and free ANS. Trends are discussed and comparisons made between bound and free fluorophore and between different isomeric ANS structures. PMID- 24242909 TI - Solvent complexes of jet-cooled beta-phenylethylamine. AB - Laser-induced fluorescence spectroscopy was used to investigate beta phenylethylamine molecules that were cooled via supersonic gas expansions. The bare molecule spectra reveal 0-0 transitions that can be attributed to four separate conformers. Upon the addition of water or alcohol solvents, a series of new peaks is induced that appear to be built off separate bare molecule transitions. This is a pattern that is markedly different from the one seen for solvent addition to tyramine, which includes an-OH in the para position. As a result, definite hypotheses can be made to explain the influence of the para-OH in affecting solvent induced conformations. PMID- 24242910 TI - Adsorption of firefly luciferase at interfaces studied by total internal reflection fluorescence spectroscopy. AB - The adsorption of luciferase onto silica surfaces was studied by total internal reflection fluorescence (TIRF) spectroscopy. Two model surfaces were used: hydrophilic and hydrophobic silica. Luciferase adsorbed differently on these two surfaces. Initial kinetics of luciferase adsorption onto the hydrophilic surface showed that luciferase adsorbs over an adsorption energy barrier of ~3 kT The quantum yield of luciferase fluorescence decreased at the hydrophilic silica surface, which indicated that the protein conformation was altered during adsorption. Luciferase adsorption onto the hydrophobic silica surface proceeded with a small adsorption energy barrier and the fluorescence efficiency of adsorbed protein remained unchanged after adsorption. The affinity of luciferase for luciferin was measured using quenching of luciferase fluorescence with luciferin. The binding constant of the adsorbed luciferase-luciferin complex at the hydrophilic silica surface was two orders of magnitude smaller than the respective binding constant in the solution. Adsorbed luciferase showed an absence of ATP-dependent visible luminescence, indicating that the adsorbed enzyme was not active at either of the two silica surfaces. PMID- 24242912 TI - Fluorescence study of a field-induced director reorientation in a liquid crystalline polyacrylate. AB - The electric field-induced director reorientation is investigated by fluorescence spectroscopy and turbidimetry. The dynamics of this reorientation are studied as a function of temperature, applied voltage, and frequency. PMID- 24242911 TI - Absorption and luminescence spectroscopic analysis of tautomeric forms of protonatedN,N-dimethyl-N'-(1-nitro-9-acridinyl)-1,3-propanediamine (nitracrine) and its nitro isomers in poly(vinyl alcohol) films. AB - The electronic absorption, fluorescence, and phosphorescence excitation spectra, as well as the fluorescence and phosphorescence spectra, at either room or liquid nitrogen temperatures, were measured forN,N-dimethyl-N'-(1-nitro-9-acridinyl)-1,3 propanediamine and its three nitro isomers in acidified poly(vinyl alcohol) (PVA) film. The spectral characteristics obtained reveal the existence of the compounds studied in at least two structural forms. The results are interpreted in terms of the tautomeric phenomena which originate due to the migration of the hydrogen atom, which is bound to the nitrogen atom attached to the carbon atom (9), to the acridine ring nitrogen. PMID- 24242913 TI - Functional implications of squamosal suture size in paranthropus boisei. AB - It has been hypothesized that the extensively overlapping temporal and parietal bones of the squamosal sutures in Paranthropus boisei are adaptations for withstanding loads associated with feeding. Finite element analysis (FEA) was used to investigate the biomechanical effects of suture size (i.e., the area of overlap between the temporal and parietal bones) on stress, strain energy, and strain ratio in the squamosal sutures of Pan troglodytes and P. boisei (specimen OH 5) during biting. Finite element models (FEMs) of OH 5 and a P. troglodytes cranium were constructed from CT scans. These models contain sutures that approximate the actual suture sizes preserved in both crania. The FEM of Pan was then modified to create two additional FEMs with squamosal sutures that are 50% smaller and 25% larger than those in the original model. Comparisons among the models test the effect of suture size on the structural integrity of the squamosal suture as the temporal squama and parietal bone move relative to each other during simulated premolar biting. Results indicate that with increasing suture size there is a decreased risk of suture failure, and that maximum stress values in the OH 5 suture were favorable compared to values in the Pan model with the normal suture size. Strain ratios suggest that shear is an important strain regime in the squamosal suture. This study is consistent with the hypothesis that larger sutures help reduce the likelihood of suture failure under high biting loads. PMID- 24242915 TI - Claudin-7 suppresses the cytotoxicity of TRAIL-expressing mesenchymal stem cells in H460 human non-small cell lung cancer cells. AB - Evidence suggests that the cytokine tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising candidate for cancer therapeutics. Studies have also shown that claudin-7 (CLDN7) expression is variably dysregulated in various malignant neoplasms, with a role in lung cancer that has not been definitively decided. This work investigated the differential sensitivity of CLDN7-overexpressing human NSCLC H460 cells to TRAIL in vitro and in mouse xenografts, and explored the molecular mechanisms responsible for these effects. NCI-H460 cells were transfected or not with green fluorescent protein-tagged CLDN7. Each group was then exposed to mesenchymal stem cells (MSCs) or red fluorescent protein-tagged MSCs transduced with lentivirus expressing membrane bound TRAIL. The effects and related mechanisms of these treatments were evaluated in vitro, and in vivo in murine xenografts. Our results indicate that TRAIL induced apoptosis in H460 cells in vitro, and in established xenograft tumors TRAIL was associated with a decrease in tumor size, tumor weight, and circulating tumor cells. CLDN7 was found to inhibit the MEK/ERK signaling pathway, leading to inhibition of death receptor 5 (TNFRSF10B). The cytotoxicity of TRAIL was confirmed in H460 cells and in vivo, and CLDN7 suppressed the cytotoxicity of TRAIL in H460 cells. Our results indicate that TRAIL may be a useful therapy to enhance apoptosis in CLDN7-negative lung cancer cells. PMID- 24242914 TI - Analgesic and antiinflammatory activities of the ethyl acetate fraction of Bidens pilosa (Asteraceae). AB - Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200 mg/kg in mice and rats, respectively. The analgesic properties of Bidens pilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (p < 0.01) reduction in pain induced by all four models of nociception. It also presented significant (p < 0.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed. PMID- 24242916 TI - Tumor suppressor Ing1b facilitates DNA repair and prevents oxidative stress induced cell death. AB - Inhibitor of growth (ING) family of proteins are known to coordinate with histone acetyltransferases and regulate the key events of cell cycle and DNA repair. Previous work from our lab showed that Ing1b regulated the nucleotide excision repair by facilitating histone acetylation and subsequent chromatin relaxation. Further, it was also shown that Ing1b protected the cells from genomic instability induced cell death by promoting ubiquitination of proliferating cell nuclear antigen (PCNA). In the present study we explored the role of Ing1b in the repair of oxidized DNA and prevention of oxidative stress induced genotoxic cell death. Using HCT116 cells we show that Ing1b protein expression is induced by treatment with H2O2. Ing1b lacking cells showed decreased ability to repair the oxidized DNA. PCNA monoubiquitination, a critical event of DNA repair was blunted in Ing1b knock down cells and augmented in Ing1b over expressing cells. Moreover, oxidative stress induced cell death was higher in cells lacking Ing1b whereas it was lower in Ing1b over expressing cells. Finally we show that inhibition of histone deacetylases, rescued the Ing1b knock down cells from cytotoxic effects of H2O2 treatment.